PMID- 7710421
TI  - [Bioactive compounds from marine actinomycetes].
AB  - Studies of the origin of bioactive metabolites of marine actinomycetes are
      reviewed. Structures and properties of new metabolites from indigenous marine
      bacteria from Actinomycetales order, such as a benzanthraquinone antibiotic from
      a strain of the Chainia purpurogena, istamycins, aplasmomycins, altemicidin, new
      phenazine esters. C13-butanolide, marinone and debromomarinone, palmyromycin,
      urauchimicins and some others compounds are presented. Prospects of marine
      biotechnology and microbiology (with considerable emphasis on the development of
      the basis biology of marine microorganisms in cultures collection) are discussed.

PMID- 7710422
TI  - [Enzymatic synthesis of peptides of arginine-chromophore substrates of
      metalloproteinases and carboxypeptidases].
AB  - Subtilisin 72 sorbed on the surface of macroporous glass catalyzes a condensation
      of the esters of N-acylated peptides with arginine derivatives in organic
      solvents. The sorbed enzyme can be used repeatedly, which makes it possible to
      synthesize the chromophore substrates of metalloproteinases and carbopeptidases
      of the general formula Dnp-Ala-Ala-Xaa-Arg-NH2 (Xaa = Leu, Phe, Val, Ile). In
      tetrapeptides, metalloproteinases hydrolyze the Ala-Xaa bond with the removal of
      Dnp-Ala-Ala-OH, which can be determined spectrophotometrically. The chromophore
      substrates of carboxypeptidases of the B type (Dnp-Ala-Ala-Xaa-Arg-OH and Dnp-Ala
      Ala-Arg-OH) are obtained by hydrolysis of the corresponding amides by trypsin.

PMID- 7710423
TI  - [The effect of certain factors on binding of tert-butyloxycarbonylamino acids to
      Merrifield polymer during interphase catalysis and assessment of racemization of
      the bound amino acid].
AB  - In order to reduce the influence of hydrogen bonds on the acylamino acid salts
      attachment to the chloromethylated resin, it is proposed to use compounds that
      can compete for the hydrogen bonds formation. The best solvent proved to be
      hexamethylphosphoric triamide. Use of interphase catalysts, e.g., tributyl-p
      nitrobenzyl ammonium, also gives good results. The racemization degree of the
      amino acids attached to solid support by means of the interphase catalysis does
      not exceed that of amino acids loaded on the polymer according to Gisin's method.

PMID- 7710424
TI  - [Synthesis of potential antimetabolites in a series of carbohydrate-modified
      pyrimidine 2'-deoxynucleosides].
AB  - The interaction of 3'-amino-2',3'-dideoxy- or 5'-amino-2',5'-dideoxy-5
      substituted pyrimidine nucleosides with N-ethylmaleimide in DMF in the presence
      of Et3N gave two diastereomeric 2',3'-dideoxy-3'-(N-ethylsuccinimido)- or 2',5'
      dideoxy-5'-(N-ethylsuccinimido)aminonucleosides in each reaction. For 3'-amino-5
      trimethylsilyl- and 3'-amino-5-benzyloxymethyl-2',5'-dideoxyuridine
      diastereomeric 3'-(N-ethylsuccinimido)derivatives were separated by preparative
      TLC. Structures of synthesized analogs were confirmed by UV-, IR- and 1H-NMR
      spectra. It has been shown that modified nucleosides at 10(-5)-10(-4) M
      concentrations do not inhibit the thymidine incorporation into DNA of CaOv cells
      in vitro.

PMID- 7710425
TI  - [3'-(Tetrazol-2''-yl-3'-deoxythymidine and its 5''-substituted form: synthesis
      and conformation in the crystalline state. Substrate properties of 3'-(tetrazol
      2''-yl)-3'-deoxythymidine-5'-triphosphate in relation to DNA polymerases].
AB  - 5''-Derivatives of 3'-(tetrazole-2''-yl)-3'-deoxythymidines were synthesized by
      interaction of 5'-benzoyl-2',3'-anhydrothymidine with tetrazole or its 5
      derivatives followed by debenzoylation. Structures of two of them, 3'-(tetrazole
      2''-yl)-3'-deoxythymidine and 3'-(5''-methyltetrazole-2''-yl)-3'-deoxythymidine,
      elucidated by X-ray analysis, revealed anti conformation of thymine about the
      glycosidic bond and 2'-endo-3'-exo-conformation of the sugar residue with gauche+
      orientation with respect to C4'-C5'-bond. 3'-(Tetrazole-2''-yl)-3'-deoxythymidine
      5'-triphosphate demonstrated poor substrate properties for the avian
      myeloblastosis virus reverse transcriptase and none for several other DNA
      polymerases.

PMID- 7710426
TI  - [Rapid detection of point mutations using biotinylated selectively cleaved
      oligonucleotides].

PMID- 7710427
TI  - [Expression vectors enabling synthesis of recombinant proteins as hybrids with
      metal-binding peptides].
AB  - Plasmid vectors providing a high level expression in Escherichia coli cells of
      genes for heterologous polypeptides and proteins fused to peptides containing
      homohistidine clusters have been constructed. The obtained vectors have been used
      to achieve expression of genes for streptavidin, proinsulin and calcitonin. The
      hybrid proteins were isolated by affinity chromatography on Ni-agarose columns.

PMID- 7710428
TI  - Bioequivalence. An updated reappraisal addressed to applications of
      interchangeable multi-source pharmaceutical products.
AB  - This paper reviews study procedures for bioequivalence trials, mainly addressed
      to the New Drug Application (NDA) of generic drugs, strictly referring to EU and
      USA guidelines on this matter. Specific attention is devoted to the most
      appropriate experimental designs, the size of the volunteer sample, the ethical
      issues involved, statistics to assess bioequivalence and the accepted standard
      format for final research reports. Some aspects which create serious problems in
      bioequivalence trials, most of which not fully covered by the EU and USA specific
      guidelines, are comprehensively discussed. These include a) drugs with elevated
      variability; b) endogeneous substances and the management of baseline value; c)
      modified release formulations; d) prodrugs; e) restrictions to be contained in
      forthcoming guidelines on chiral medicinal products; f) superbioavailability; g)
      drugs with elevated half-life and h) cases in which bioequivalence trials should
      not be needed. As generic drugs cost less than the innovator product, agencies
      have facilitated their NDA procedures by requiring a dossier on chemistry and
      pharmacy and a pivotal bioequivalence study to demonstrate that the generic
      formulation is fully interchangeable with the innovator product. Bioequivalence
      is thus the key requirement for an NDA of a generic drug, and trials should be
      planned, conducted and reported in the most appropriate way. With this in mind,
      this review is an up-to-date reappraisal that should stimulate the attention of
      scientists and regulatory authorities on some open questions on bioequivalence.

PMID- 7710429
TI  - Synthesis and opioid activity of tyrosine sulfate containing dermorphin and
      deltorphin peptides.
AB  - To study the effect of the sulfate ester moiety on the opioid activity, we
      prepared two tyrosine sulfate-(Tyr(SO3H)-containing dermorphin and deltorphin
      peptides. Their activities were determined in binding studies based on
      displacement of mu- and delta-receptor selective radiolabels from rat brain
      membranes and in two bioassays, using guinea pig ileum and mouse vas deferens. In
      comparison to original peptides and morphine, the obtained data indicate that
      whereas H-Tyr(SO3H)-D-Ala-Phe-Gly-NH2 shows very minimal interaction with opioid
      receptors, H-Tyr(SO3H)-D-Ala-Phe-Asp-Val-Val-Gly-NH2 retains a significant
      activity.

PMID- 7710430
TI  - Effects of flumazenil on ethanol withdrawal syndrome in rats.
AB  - Effects of flumazenil (Ro 15-1788, CAS 78755-81-4) on ethanol withdrawal syndrome
      (EWS) has been investigated in rats. Behavioral EWS symptoms appeared during the
      first 6 h of ethanol withdrawal. Flumazenil (2.5 and 10 mg/kg i.p.) increased
      horizontal and vertical locomotor activity significantly and also precipitated
      abnormal gait and agitation at the beginning of EWS in a dose dependent manner.
      However, thereafter it reduced the severity of abnormal posture and gait, tail
      stiffness, agitation and stereotyped behavior in a dose dependent manner. At the
      6th hour of EWS, flumazenil (10 mg/kg) reduced total EWS score significantly, but
      shortened the latency of audiogenic seizures and increased the severity of wet
      dog shakes. Flumazenil (2.5 and 10 mg/kg) did not elicit behavioral EWS symptoms
      and audiogenic seizures in non-dependent (control) rats. It did not cause any
      significant change on locomotor activities in these groups. According to those
      results, certain actions of flumazenil on the experimental EWS may suggest a
      potential beneficial effect of this drug in the treatment of EWS in alcoholics,
      but its enhancing effects on some behavioral EWS symptoms and a potential
      proconvulsant activity may be a drawback for its use in the treatment of EWS.

PMID- 7710431
TI  - Sedative action of extract combinations of Eschscholtzia californica and
      Corydalis cava.
AB  - The herbal drug Phytonoxon N (abbreviated as PN) is indicated in nervousness
      induced insomnia, agitation and/or anxiety. It is composed of alcoholic drug
      extracts of the plants Corydalis cava (20%) and Eschscholtzia californica (80%).
      Both plants are rich in isoquinoline alkaloids derived from tyrosine metabolism.
      Recent research shows that they may influence the neurotransmitter metabolism.

PMID- 7710432
TI  - Modulation of key reactions of the catecholamine metabolism by extracts from
      Eschscholtzia californica and Corydalis cava.
AB  - Aqueous-alcoholic extracts from Eschscholtzia californica inhibit the enzymatic
      degradation of catecholamines as well as the synthesis of adrenaline, whereas
      aqueous-ethanolic extracts from Corydalis cava enhance the chemical oxidation of
      adrenaline and the synthesis of melanine from dihydroxyphenylalanine (DOPA). Both
      extracts dramatically shorten the lag phase in the catalysis of phenolase
      probably due to their o-diphenol content, where the Corydalis extracts are 10
      times more active than the Eschscholtzia preparations. Dopamine beta-hydroxylase
      and monoamine oxidase (MAO-B) are especially inhibited by Eschscholtzia extracts.
      Diamine oxidases are inhibited by both preparations to a similar extent. The
      results of this study may be interpreted as a cooperative function of the two
      preparations in establishing and preserving high catecholamine levels thus
      explaining their sedative, antidepressive and hypnotic activities.

PMID- 7710433
TI  - Effects of ethanolic extracts from Eschscholtzia californica and Corydalis cava
      on dimerization and oxidation of enkephalins.
AB  - The endogenous pentapeptides, met-enkephalin and leuenkephalin, similar to their
      parent structures, beta-endorphin or dynorphin, bind to opioid receptors of the
      nociceptive system thus provoking analgesic responses. Peroxidases and phenolases
      (tyrosinase, catecholase) were shown to dimerize these pentapeptides thus
      possibly modulating their activity and/or lifetime. Extracts from plants from the
      order of the Papaverales contain isoquinoline alkaloids. Since the
      benzoisoquinolines are known to possess sedative-hypnotic activities, the
      potential effects of extracts from two species from this plant group,
      Eschscholtzia californica (Papaveraceae) and tyrosinase-catalyzed dimerization
      and/or oxidation of met-enkephalin were investigated. The results of the study
      show that the peroxidase-catalyzed dimerization via the tyr-residues is
      especially inhibited by the C. cava extract. The tyrosinase-catalyzed reaction
      yields five different products A-E, according to their HPLC-retention times.
      Consisting of the 4:1 (v/v) combination of the extracts from E. californica and
      C. cava, Phytonoxon N (abbreviated as PN) stimulates the formation of minor
      products A, B and E, whereas the formation of the major products C and D is
      inhibited. Only products C and D exhibit properties similar to the peroxidase
      derived dimer. Product A is likely to be identical to DOPA-enkephalin.

PMID- 7710434
TI  - Effects of pimobendan and its metabolite on myofibrillar calcium responsiveness
      and ATPase activity in the presence of inorganic phosphate.
AB  - The effects of the cardiotonic agent pimobendan (CAS 118428-36-7, UD-CG 115 BS)
      and its main metabolite UD-CG 212 on dog cardiac myofibrillar calcium
      responsiveness and ATPase activity were studied at nominal free inorganic
      phosphate (Pi) and at 5 mmol/l Pi. A rightward shift of the pCa-tension
      relationship with a marked depression of maximal tension was observed in the
      presence of 5 mmol/l Pi. Pimobendan increased myofibrillar calcium responsiveness
      at concentrations > or = 10(-5) mol/l. These effects of pimobendan were
      significantly greater at 5 mmol/l Pi than at nominally free Pi. UD-CG 212 had no
      influence on myofibrillar calcium responsiveness at nominally free Pi, however,
      significant effects were observed at 10(-9) mol/l UD-CG 212 in the presence of 5
      mmol/l Pi. UD-CG 212 (10(-8) mol/l) did not influence myofibrillar ATPase
      activity at pCa's 6.23, 5.99, and 4.36 with or without 5 mmol/l Pi, whereas
      pimobendan (10(-4) mol/l) had an effect only at pCa = 5.99 (without Pi) and pCa =
      4.36 (+ 5 mmol/l Pi). The data suggest that the increase in myofibrillar calcium
      responsiveness at submaximal calcium concentrations by pimobendan and UD-CG 212
      in the presence of 5 mmol/l Pi is brought about by a change in cross-bridge
      kinetics or by enhancement of thin filament activation by adjacent strong cross
      bridges. At maximal calcium activation, pimobendan may additionally increase the
      population of strong cross-bridges.

PMID- 7710435
TI  - Evaluation of the pharmacokinetics and absolute bioavailability of three
      isosorbide-5-mononitrate preparations in healthy volunteers.
AB  - The objective of this study was two-fold: 1. to determine the pharmacokinetic
      parameters and the bioavailability of two 20 mg isosorbide-5-mononitrate (CAS
      16051-77-7, IS-5-MN) preparations (treatments A and B) after single oral
      administration and 2. to evaluate the absolute bioavailability of IS-5-MN, which
      was possible by the administration of a third IS-5-MN preparation (treatment C)
      by the intravenous route (1 mg/ml, dose 20 mg). The three preparations were
      examined in 24 healthy volunteers according to a randomized 3-way cross-over
      design, blood samples were withdrawn up to 24 h following the administration of
      IS-5-MN and plasma concentrations of IS-5-MN were quantified by a gas
      chromatography method. The two oral preparations led to peak concentration values
      of about 360 ng/ml of IS-5-MN in the mean 0.90 h (treatment A) and 0.97 h
      (treatment B) after drug administration. The corresponding values for the
      infusion were 339.6 ng/ml and 2.59 h in the mean. For the areas under the curve
      (AUC(0-infinity)) mean values of 2733 (treatment A). 2724 (treatment B) and 2877
      h x ng/ml (treatment C) were found. The absolute bioavailability of both oral
      treatments revealed values of 95.00% and 94.74% for treatments A and B,
      respectively. The statistical comparison (ANOVA, confidence intervals) of the
      pharmacokinetic parameters showed bioequivalence between both oral preparations
      and equivalence in the amount of drug absorption between both oral formulations
      and the i.v.-infusion. The observed undesired side effects (e.g. headache or
      nausea) are well known to occur after IS-5-MN administration.

PMID- 7710436
TI  - Pharmacokinetic parameters of verapamil and its active metabolite norverapamil in
      patients with hepatopathy.
AB  - Verapamil (CAS 52-53-9) is a calcium channel blocker with a vasodilatatory
      effect. Because of its significant first-pass effect, verapamil might be
      advantageous in the treatment of portal hypertension. It does not produce any
      excessive systemic effects, provided the doses are suitably adjusted. A decision
      was made to examine the pharmacokinetic parameters, independent of compartmental
      analysis of verapamil and its active metabolite norverapamil, in patients with
      portal hypertension. Their biological half-lives of the terminal phase were
      significantly prolonged as compared with the control group. However, no
      statistically significant differences were found in the values of tmax and Cmax.
      The calculated pharmacokinetic parameters of norverapamil were not significantly
      different from those of verapamil, except for the tmax of norverapamil, which was
      significantly longer in patients suffering from portal hypertension as compared
      with verapamil. The ratio of areas under the plasma concentration-time curve
      (AUC) of verapamil and norverapamil was comparable in both groups of patients. No
      relationship between the changes in the pharmacokinetic parameters and the extent
      of hepatic insufficiency was observed.

PMID- 7710437
TI  - Synthesis and inhibitory activities on platelet aggregation of some flavonoid
      analogues.
AB  - A series of 26 benzodioxan and benzodioxol derivatives of flavone have been
      prepared. The activity of the compounds on washed human platelet aggregation
      induced by adenosine diphosphate (ADP, 5 mumol/l), collagen (10 micrograms/ml)
      and calcimycin (20 mumol/l) was evaluated. The alkoxycarbonyl side chain
      derivatives inhibited all three types of aggregation inducers. Among the tested
      compounds Ia is the most potent inhibitor of collagen-induced aggregation but
      possesses a weak activity against the other two used inducers. The esters IIIb
      and in particular, IIIc are active against all the three used inducers. These
      results suggest that ethoxycarbonyl group is a potent substituent to provide the
      antiplatelet action in this series of flavonoids.

PMID- 7710438
TI  - Effect of the lipoxygenase inhibitor N-hydroxy-N-(6-methoxy-3,4-dihydro-2
      naphthylmethyl)urea on bronchoconstriction and lung vascular permeability in
      anaphylactic guinea pigs.
AB  - Narrowing of the airway lumen as a result of plasma exudation could augment
      airflow obstruction after allergen-induced bronchoconstriction. Because
      leukotrienes are putative mediators of bronchial asthma, the effects of a
      lipoxygenase inhibitor, VZ564 (N-hydroxy-N-(6-methoxy-3,4-dihydro-2-
      naphthylmethyl) urea. CAS 147495-99-6), on increased pulmonary permeability and
      bronchoconstriction during anaphylactic reaction were studied in guinea pigs and
      compared to the effects of the phosphodiesterase inhibitor theophylline. An
      anaphylactic reaction was induced by ovalbumin challenge (0.2 mg/kg i.v.) in
      passively sensitized and antihistamine (mepyramine)-pretreated guinea pigs;
      bronchoconstriction was measured as increased intratracheal pressure; lung
      vascular permeability was evaluated as extravasation of Evans blue dye up to 10
      min after antigenic challenge. Ovalbumin challenge induced an increase in
      intratracheal pressure by 31 +/- 3 mmHg; the pulmonary permeability index was
      higher in ovalbumin-challenged versus saline (sham)-challenged guinea pigs (1.49
      +/- 0.17 vs 0.56 +/- 0.04, p < 0.05). VZ564 and theophylline dose-dependently
      reduced increased pulmonary permeability and bronchoconstriction. VZ564 (10 and
      46.4 mg/kg p.o., given 1 h before ovalbumin challenge) inhibited increased lung
      permeability by 42% and 95% and reduced bronchoconstriction by 61% at the higher
      dose. Theophylline (1 and 10 mg/kg i.v., given 10 min before ovalbumin challenge)
      diminished increased pulmonary permeability by 88% and reduced
      bronchoconstriction by 63% at the higher dose. In conclusion, the novel
      lipoxygenase inhibitor VZ564 inhibits after oral application important symptoms
      of asthma, namely bronchoconstriction and alveolar exudation of plasma in
      anaphylactic guinea pigs. The acute effects of VZ564 in this experimental model
      are comparable with the effects of the well known antiasthmatic substance
      theophylline.

PMID- 7710439
TI  - General pharmacology of [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3- dihydro-1H
      pyrrolizine-5-yl]-acetic acid in experimental animals.
AB  - [2,2-Dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5- yl]
      acetic acid (ML 3000) is a newly synthesized compound with analgesic, antipyretic
      and anti-inflammatory activity. The general pharmacological effects of ML 3000
      following oral administration were investigated in experimental animals. The
      results showed that with regard to the CNS, ML 3000 did not affect behaviour in
      the Irwin test, locomotor activity or hexobarbital-induced sleep at doses of 30,
      100 and 300 mg/kg. ML 3000, at a single dose of 100 mg/kg administered
      intraduodenally, had no notable effect on the cardiovascular system or
      respiration in anaesthestised rats and dogs nor on neuromuscular function in
      anaesthetised cats. No evidence of gastric damage or disturbance of peristalsis
      was observed following oral administration of ML 3000. In vitro, ML 3000 evoked a
      weak spasmogenic response in the guinea-pig ileum with a dose-related inhibition
      of acetylcholine, histamine and barium chloride-induced responses. A small
      transient reduction in urine volume was observed after the highest dose
      accompanied by decreases in electrolyte excretion at doses of 100 and 300 mg/kg
      in rats. The results demonstrate that ML 3000 has no notable general
      pharmacological effects under the experimental conditions reported.

PMID- 7710440
TI  - Anti-inflammatory, spasmolytic and diuretic effects of a commercially available
      Solidago gigantea Herb. extract.
AB  - The evaluation of a commercially available Solidago gigantea Herb. extract (Urol
      mono) revealed pronounced anti-inflammatory properties in the rat with respect to
      a reduction of the carrageenin-induced rat paw oedema. A direct comparison with
      diclofenac-Na (3 mg/kg b.w. p.o.) revealed that a high dose of Solidago gigantea
      Herb. extract possesses the same anti-inflammatory efficacy as diclofenac-Na. In
      addition, the Solidago gigantea Herb. extract exhibited moderate spasmolytic and
      diuretic properties.

PMID- 7710441
TI  - A combination of Populus tremula, Solidago virgaurea and Fraxinus excelsior as an
      anti-inflammatory and antirheumatic drug. A short review.
AB  - Anti-inflammatory properties of Populus tremula are mainly deduced from its
      components, the well investigated salicylates. Solidago extracts have
      spasmolytic, antihypertensive and diuretic effects. Fraxinus excelsior itself has
      hardly been investigated, but its coumarin components proved to have a variety of
      pharmacological properties, i.e. inhibition of T-cell activation and of the
      arachidonic acid cascade. Phytodolor N (abbreviated as PD) is a combination of
      the above mentioned plants. Various in vitro and especially in vivo studies
      proved its anti-inflammatory and antirheumatic properties, often comparable to
      non-steroidal anti-inflammatories, but with little or no side effects.

PMID- 7710442
TI  - Inhibition of dihydrofolate reductase activity by alcoholic extracts from
      Fraxinus excelsior, Populus tremula and Solidago virgaurea.
AB  - Aqueous-ethanolic extracts of Fraxinus excelsior, Populus, tremula and Solidago
      virgaurea in a combination of 1: 3: 1 (v/v/v) are the components of the plant
      drug Phytodolor N (abbreviated as PD), which exhibits antipyretic, analgesic and
      antirheumatic activity. Similar to a broad variety of synthetic non-steroidal
      anti-inflammatories the mentioned plant extracts inhibit dihydrofolate reductase.
      The following concentrations as percentage in the test volumes represent the
      individual I50-values: F. excelsior = 0.26% (v/v); P. tremula = 0.46% (v/v) and
      S. virgaurea = 0.6% (v/v). The combined extracts in PD exhibit an I50 at 0.3%
      (v/v). Testing the activity of the water-soluble compounds of corresponding dry
      extracts, the activity of F. excelsior with an apparent I50-value of 0.008% (w/v)
      by far dominates the inhibitory overall effect of the combination (I50 = 0.014%,
      w/v).

PMID- 7710443
TI  - Antioxidative properties of alcoholic extracts from Fraxinus excelsior, Populus
      tremula and Solidago virgaurea.
AB  - Aqueous-ethanolic extracts from Fraxinus excelsior, Populus tremula and Solidago
      virgaurea inhibit biochemical model reactions representing inflammatory
      situations to various extents. These model reactions include xanthine oxidase,
      diaphorase in the presence of the autoxidizable quinone juglone, lipoxygenase and
      photodynamic reactions driven by riboflavin or rose bengal. The tested extracts
      are the components of the phytomedicine Phytodolor N (abbreviated as PD) which
      possesses antipyretic, analgesic, antiinflammatory and antirheumatic activity.
      Since several reactive oxygen species produced by the mentioned model systems are
      also involved in inflammatory processes, the beneficial activities of the
      complete drug may at least in part be due to the reported antioxidative functions
      of the individual components.

PMID- 7710444
TI  - Single dose pharmacokinetics and tolerance of pancopride in healthy volunteers.
AB  - Pancopride (LAS 30451, CAS 121650-80-4) is a new selective 5-hydroxytryptamine3
      receptor antagonist which has demonstrated antiemetic properties in animal
      models. The tolerance and pharmacokinetics of pancopride and its effect on the 5
      hydroxytryptamine flare test were examined in healthy male volunteers, in three
      single-dose studies. The studies consisted of two rising dose tolerance and
      kinetic studies with placebo control, each involving 14 volunteers, and an
      absolute bioavailability study involving 12 volunteers. The doses used in the
      rising dose studies were 0.5-20 mg intravenous pancopride in the first study, and
      5-40 mg pancopride as oral solution in the second study. For the absolute
      bioavailability study, 20 mg doses as intravenous infusion, oral tablet and oral
      solution were compared. Pancopride was well tolerated at these doses in these
      studies. There were no significant effects on pulse rate, blood pressure, or
      electrocardiograms, or on haematology or serum biochemistry. Few adverse events
      were recorded, the most significant being gastrointestinal effects (including
      diarrhoea and soft stools) seen particularly with the 40 mg oral dose.
      Pharmacokinetic parameters for the 24 h after dosing were derived from plasma and
      urine pancopride levels, determined using a capillary gas chromatography-mass
      spectrometry method. Linear kinetics appeared to apply over the intravenous dose
      range 5-20 mg. Urinary recovery of unchanged pancopride was in the order of 10
      17% over the 24 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7710445
TI  - [Ranitidine and clarithromycin for eradication of Helicobacter pylori in patients
      with duodenal ulcer].
AB  - To compare the efficacy of ranitidine (CAS66357-35-5, Sostril) in combination
      with clarithromycin (CAS 81103-11-9, Cyllind) against H. pylori, a controlled
      randomized double-blind study was carried out. Fourty duodenal ulcer patients
      were treated either with ranitidine 150 mg b.i.d. and clarithromycin 500 mg
      q.i.d. (20 patients, group 1) or ranitidine 300 mg q.i.d. and clarithromycin 500
      mg q.i.d. (20 patients, group 2) for 14 days. Both treatment groups received an
      additional treatment with ranitidine 300 mg daily for another 14 days. Endoscopy
      6 weeks after the beginning of the trial showed complete ulcer healing in all
      patients. The control of H. pylori status done by CLO (Campylobacter-like
      organism) test and histology yielded an eradication rate of 84% (group 2) and 61%
      (group 1) in patients with duodenal ulcer disease treated with ranitidine and
      clarithromycin. Whether higher suppression of gastric acidity with a higher dose
      of ranitidine in combination with the antibiotic clarithromycin presents clear
      advantages in eradication of H. pylori should be investigated in further studies.

PMID- 7710446
TI  - Pharmacokinetics of fenoterol in pregnant women.
AB  - The beta 2-sympathomimetic drug fenoterol (fenoterol hydrobromide, CAS 1944-12-3,
      Partusisten) is routinely used to inhibit uterine contractions (tocolysis).
      Investigations of plasma concentrations of those receiving i.v. or oral tocolysis
      often show different results, both within particular groups of pregnant women and
      in comparison with non-pregnant persons. The aim of this study was to determine
      the pharmacokinetics of fenoterol in pregnant women, an important factor which so
      far had not been known. Four healthy pregnant women with similar weight and
      gestational age and all with premature labor were administered a continuous
      intravenous infusion of 4 micrograms fenoterol/min. During and up to 24 hours
      after the end of the infusion, venous blood samples were taken in order to
      determine the fenoterol plasma concentrations by radioimmunoassay. From a steady
      state concentration (css) of 2242 +/- 391 pg/ml (x +/- S.E.), a non-linear two
      phased plasma elimination was seen with half-lives t1/2 of 11.40 min and 4.87 h.
      The area under the plasma concentration-time curve (AUC0-12h) was 6.27 ng/ml x h.
      The total clearance (Cltot) was 114.8 l/h. These data are nearly the same as the
      data already known for healthy non-pregnant (male) volunteers. The deviations
      which are seen in the plasma concentrations in pregnant women in comparison to
      non-pregnant persons during or after continuous i.v. infusion can therefore not
      be caused by differences in the pharmacokinetics. Other factors, however, such as
      body weight and/or gestational age, might influence the results.

PMID- 7710447
TI  - Synthesis and preliminary in vitro evaluation of antitumor nitrosoureido
      cholesterol derivatives.
AB  - A new class of chloroethyl nitrosourea analogues of cholesterol has been
      synthetized from the corresponding 7-amino and 7-aminoalkylcholesterol
      derivatives. Compounds III-V inhibited L1210 cell growth in culture much more
      effectively than N,N'-bis(2-chloroethyl)-N'-nitrosourea (BCNU) after 48 h
      incubation. Stability and cytotoxic activity of these prodrugs are promising for
      brain tumor treatments and as lymphotropic vectors for tumor cells spreading
      along the lymphatic pathways.

PMID- 7710448
TI  - Reduction of in vitro clastogenicity induced by the mixture of optical isomers of
      nadifloxacin during storage.
AB  - The fluoroquinolone antibacterial agent, nadifloxacin (NDFX, CAS 124858-35-1), is
      a racemic compound. The storage effect on the in vitro clastogenicity of a
      solution of the racemic compound and a mixture solution of the optical isomers of
      NDFX, prepared by mixing equal amounts of S- and R-enantiomers, was investigated.
      The potential of NDFX and the enantiomer mixture, prepared from equal amounts of
      each S- and R-enantiomer, to induce chromosomal aberrations in vitro was
      investigated in cultured fibroblasts derived from Chinese hamster lung cells
      immediately, 2 and 4 weeks after preparation of the test solutions (stored at 20
      degrees C, protected from light) using 24 h of continuous treatment method. In
      the results, NDFX did not significantly increase the incidence of chromosomal
      aberrations at 200 micrograms/ml regardless of the storage period. On the other
      hand, the mixture significantly increased the incidence of chromosomal
      aberrations at 200 micrograms/ml immediately after preparation to an extent
      similar to that of S-enantiomer alone, but the mixture did not do so after 2 and
      4 weeks of storage. Neither S- nor R-enantiomer changed the chromosomal
      aberration inducibility during storage. The content and optical purity of the
      test substances in each test solution also did not change during storage. These
      facts suggested that the molecular condition of each optical isomer in the
      mixture solution became equivalent to that in the racemic solution during storage
      periods.

PMID- 7710449
TI  - Efficacy of new organic ammonium salts on Pseudomonas aeruginosa Salmonella
      typhimurium.
AB  - The inhibitory activities of four new homologous series of organic ammonium salts
      (OAS) were tested on bacterial strains isolated from patients. Two types of
      compounds are used: "hard" (group A) and three groups (B, C, D) of biodegradable
      "soft" OAS with metabolically labile CO or NH groups in their molecules. The
      strain Pseudomonas aeruginosa was isolated from the sputum of a patient with
      carcinoma. The strain Salmonella typhimurium was isolated from a patient with
      clinical diagnosis of diarrhea. In all homologous series, the antibacterial
      activity was increasing continuously with the length of alkyl chain up to dodecyl
      or tetradecyl, then the "cut off" effect was observed. The most active compounds
      from both "hard" and "soft" types had superior activity to commercial
      disinfectants. The strain of Pseudomonas aeruginosa was more sensitive to these
      compounds than that of Salmonella typhimurium.

PMID- 7710450
TI  - Comparison of iopamidol and ioversol in vitro and in animal studies.
AB  - In the present series of studies we investigated differences in vitro and in
      animal experiments between iopamidol (Iopamiron, CAS 60166-93-0) and ioversol
      (CAS 87771-40-2). The studies included the in vitro investigations partition
      coefficient, lysozyme inhibition, coagulation time and erythrocyte morphology as
      well as the in vivo paradigms acute toxicity, neural toxicity, general
      behavior/locomotor activity and angiography. Iopamidol was superior to ioversol
      in most of the tests. In spite of its higher hydrophilicity, ioversol did not
      show improved tolerance in comparison to iopamidol.

PMID- 7710451
TI  - Conventional statistics and useful statistics.
AB  - Differences between conventional statistical methods and more useful, modern
      methods are demonstrated using a statistical analysis of data from therapeutic
      research in rheumatology. The conventional methods, t-test and graphs of mean
      values and the boxplot, detect almost no differences between treatment groups. A
      more recent procedure for analysing group differences is the Wilcoxon-Mann
      Whitney test. The associated graphs are based on the cumulative distribution
      function of the two treatment groups and the synthetic Receiver Operating
      Characteristic (ROC). Special differences, namely baseline dependencies, can be
      visualized in this way.

PMID- 7710452
TI  - Pharmacokinetic drug interaction between epirubicin and interferon-alpha-2b in
      serum and red blood cells.
AB  - The influence of interferon-alpha-2b (CAS 99210-65-8, IFN) on the
      pharmacokinetics of epirubicin (CAS 56420-45-2, EPR) was investigated in 10
      patients (4 male, 6 female). EPR was injected as an i.v. bolus over 2 min in a
      dose of 60 mg/m2 IFN was pre-administered 3 times a week in a dose of 5 x 10(6)
      IU as a s.c. injection. The comparison of the pharmacokinetics after injection of
      EPR and EPR+IFN did not show remarkable differences. A statistical significant
      influence in regard to the terminal elimination half-life (gamma-HL) and the
      total clearance (CLtot) was found, indicating a reduction of gamma-HL from 18.18
      +/- 16.7 for EPR to 8.47 +/- 8.67 h for EPR+IFN and a reduction of the total
      clearance from 72.33 +/- 55.4 ml/min for EPR to 48.41 +/- 12.7 ml/min for
      EPR+IFN. The area under the concentration-time curve (AUC, according to the 3
      compartment model) increases under the influence of IFN from 2004 +/- 1105
      ng/ml.h for EPR up to 2582 +/- 1024 ng/ml.h for EPR+IFN. However, this increase
      is statistically irrelevant due to the high deviation ranges. Besides, the
      influence of IFN on the interactions of EPR with red blood cells (RBCs) was
      investigated in 6 patients under the above conditions. The percental
      concentration of EPR in RBCs is reduced from 35.4% to 34.7% after administration
      of IFN. Two metabolites, 13-dihydroepirubicin (M I) and 7-deoxydoxorubicinone (M
      II), were detected both in serum and RBCs, whereas IFN showed no significant
      interference with the metabolism or with the binding of the metabolites to RBCs.

PMID- 7710453
TI  - Incidence of community-acquired pneumonia and Chlamydia pneumoniae infection: a
      prospective multicentre study.
AB  - This one year prospective multicentre study was designed to determine the
      incidence of community-acquired pneumonia in adults. It was carried out in
      primary health care centres and three reference hospitals, located in the
      'Maresme' region (Barcelona, Spain) serving a population of 39,733 subjects over
      13 years of age. Patients suspected of having contracted community-acquired
      pneumonia were visited by their family doctors and referred to the three
      reference hospitals for confirmation of the diagnosis. Patients attending the
      emergency services of these hospitals were also included. Urine and blood samples
      were obtained for culture, antigen detection, blood count, serological tests,
      blood gases and biochemical profile. The diagnosis of community-acquired
      pneumonia was made in 105 patients. Forty-six patients had an identifiable
      microbial etiology. Chlamydia pneumoniae was the most common pathogen (16 cases)
      followed by Streptococcus pneumoniae (13 cases) and Mycoplasma pneumoniae (8
      cases). In conclusion; the annual incidence rate of community-acquired pneumonia
      in adults in this area was 2.6 cases per 1,000 inhabitants and Chlamydia
      pneumoniae was the most frequent causative pathogen.

PMID- 7710454
TI  - Basophilic differentiation in acute promyelocytic leukemia.
AB  - A rare variant of acute promyelocytic leukemia (APL) is associated with
      basophilic differentiation. Such a patient presented with basophilia, headaches,
      and diffuse engorgement of superficial blood vessels, attributable to
      hyperhistaminemia. Karyotype analysis showed a clonal rearrangement of chromosome
      12p13 in addition to the t(15;17). During treatment with all-trans-retinoic acid
      (TRA), the absolute basophil count rose steadily during the first week, then
      declined. By one month, the basophilia resolved, an abrupt rise occurred in both
      the platelet and absolute neutrophil count, and the bone core biopsy showed
      complete maturation of all cell lines. Abnormalities of chromosome 12p13 in acute
      myelogenous leukemia have been associated with basophilia. Since every cell in
      our patient with t(12p13;?) also had the t(15;17), we speculate that the
      basophilia was due to clonal evolution with acquisition of the t(12p13;?). In two
      out of five other reported cases, abnormalities of chromosomes known to be
      associated with basophilia were present in addition to t(15;17). It is possible
      that the basophilia in this variant is reactive; however, since TRA induces
      differentiation of leukemic promyelocytes into mature neutrophils, we speculate
      that the leukemic promyelocytes in our patient differentiated into basophils.
      Future studies employing either fluorescent in situ hybridization or polymerase
      chain reaction using a probe to the breakpoint on t(15;17) may establish whether
      or not the basophils derive from the leukemic clone.

PMID- 7710455
TI  - Surface topography of soft contact lenses for neutralizing corneal astigmatism.
AB  - We compared the surface topography of 38 soft contact lenses in situ to the
      corneal topography of 17 patients. The analyzed lenses consisted of patients'
      spherical and toric lenses as well as additional spherical lenses of various
      thicknesses. Thirteen brands of contact lenses were worn; corneal astigmatism
      ranged from 0.12 to 3.81 D. Our hypothesis was that toric soft contact lens
      neutralization of corneal surface astigmatism occurred through the creation of a
      more spherical anterior surface. Videokeratoscopy was used to analyze corneal
      surface changes with contact lens wear. The correction of astigmatism for toric
      corneas (toricity > 0.75 D) fit with toric lenses (i.e., the difference between
      the surfaces of the cornea and anterior lens) showed surface astigmatism
      neutralization of only 34 +/- 38%. The greater the astigmatism, the greater the
      neutralization. Spherical lenses not only failed to mask corneal toricity, but
      actually increased it. The topographic map can be a valuable asset for analyzing
      and possibly improving contact lens fitting of toric contact lenses.

PMID- 7710456
TI  - Decreasing mortality associated with the introduction of surfactant therapy: an
      observational study of neonates weighing 601 to 1300 grams at birth. The Members
      of the National Institute of Child Health and Human Development Neonatal Research
      Network.
AB  - OBJECTIVE: To determine whether the introduction of surfactant therapy was
      associated with decreased mortality for high-risk preterm neonates weighing 601
      to 1300 g at birth. DESIGN: Before-after observational study. SETTING: Eight
      tertiary care neonatal intensive care units participating in the National
      Institute of Child Health and Human Development Neonatal Research Network.
      PATIENTS: The outcomes for neonates with birth weight 601 to 1300 g admitted in
      the 2 years before surfactants became available (n = 2780) were compared with
      those of neonates admitted in the year beginning 2 months after surfactants
      became available (n = 1413). MAIN OUTCOME MEASURES: The primary outcome measure
      was in-hospital mortality; secondary outcome measures included durations of
      assisted ventilation, length of hospitalization, and neonatal morbidity. RESULTS:
      Forty percent of neonates in the postsurfactant group received surfactant (range
      28% to 69% at the centers). Mortality decreased from 27.8% before to 19.9% after
      surfactant therapy was introduced (Mantel-Haenszel chi 2 = 31.4, P = .001). The
      adjusted odds ratio for mortality after surfactants became available was 0.73
      (95% confidence interval 0.55 to 0.95). The duration of assisted ventilation and
      length of hospitalization increased after surfactants were introduced (P = .0001
      for both outcomes). CONCLUSION: Mortality for neonates weighing 601 to 1300 g
      decreased after surfactant therapy was introduced, suggesting that the efficacy
      of surfactants demonstrated in randomized controlled trials will translate into
      effectiveness in routine clinical care.

PMID- 7710457
TI  - [Idiopathic segmental infarction of the great omentum. Apropos of the article by
      Giuly et al].

PMID- 7710458
TI  - [The therapeutic washout in the stress test].

PMID- 7710459
TI  - [Hepatitis C virus: an improbable etiological agent of Gougerot-Sjogren's
      syndrome].

PMID- 7710460
TI  - Cytomegalovirus infection and risk of AIDS in human immunodeficiency virus
      infected hemophilia patients. National Cancer Institute Multicenter Hemophilia
      Cohort Study Group.
AB  - The effects of prevalent and incident cytomegalovirus (CMV) infection on human
      immunodeficiency virus (HIV) disease progression were examined in 393 hemophilia
      patients with known dates of HIV seroconversion. Of the cases, 191 (49%) had IgG
      antibody to CMV in their earliest stored sera (median date, November 1983). CMV
      seropositive subjects were one and a half times more likely to develop AIDS, and
      they were also older than CMV-negative subjects. Adjusted for age, CMV
      seropositivity was not associated with the development of AIDS. In age-adjusted
      analyses, CMV-seropositive subjects had a small, but statistically insignificant,
      decrease in survival after HIV seroconversion. Older subjects were more likely to
      CMV seroconvert by the time of their latest available serum samples (P = .03).
      CMV seroconverters were five times more likely to develop clinical CMV disease
      than were subjects initially CMV-positive (P = .02). To avoid this source of
      serious morbidity, CMV-seronegative hemophiliacs with HIV infection should not be
      exposed to cellular blood products or body fluids from CMV-seropositive donors.

PMID- 7710461
TI  - Increases in type III collagen gene expression and protein synthesis in patients
      with inguinal hernias.
AB  - OBJECTIVE: The aim of this study was to determine if alterations in fibrillar
      collagen synthesis were associated with the development of inguinal hernias.
      SUMMARY BACKGROUND DATA: Previous work has suggested that alterations in
      connective tissue accumulation may play a functional role in the development of
      inguinal hernias. In particular, several investigators have suggested that
      alterations in collagen synthesis, causally related to connective disorders such
      as osteogenesis imperfecta, may also be responsible for the inguinal herniation
      that is markedly increased in such patients. This study was undertaken therefore
      to study collagen synthesis in patients with inguinal hernia in the absence of
      any other connective tissue disease. METHODS: Skin fibroblasts from 9 patients
      with hernias and 15 control individuals were radiolabeled with 3H-proline.
      Trypsin-chymotrypsin-resistant type I and III collagens were isolated and
      analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and
      recovery was quantified by laser densitometry. Steady-state levels of alpha 1(I)
      and alpha 1(III) procollagen mRNAs were also determined by northern and slot-blot
      hybridization analysis. RESULTS: The alpha 1(I)/alpha 1(III) collagen ratios were
      shown to be 6.3 +/- 0.34 in fibroblasts from control individuals and 3.0 +/- 0.25
      in fibroblasts from patients with inguinal hernias. This statistically
      significant difference (p < 0.0001) was caused by an increase in the secretion of
      alpha 1(III) procollagen from the fibroblasts of patients with hernias. A
      concomitant increase in the steady-state levels of alpha 1(III) procollagen mRNA
      was observed in total RNA isolated from the patients' fibroblasts. CONCLUSIONS: A
      constitutive and systemic increase in type III collagen synthesis may result in
      reduced collagen fibril assembly in the abdominal wall, eventually leading to the
      development of herniation. Although it is not yet clear what genetic factors are
      responsible for the elevation in type III collagen synthesis in patients with
      hernias, this study represents the first attempt to define individuals with an
      abnormality in collagen production that may be specifically related to
      herniation. A clearer understanding of the possible genetic factors that
      influence the pathophysiology of this disease will be important to improve the
      treatment of patients in whom inguinal hernias develop.

PMID- 7710462
TI  - Praxis makes perfect?
AB  - Hospital formulary committees blend cost-effectiveness analysis, peer review, and
      continuing medical education to regulate hospital drug purchases and physicians'
      prescribing patterns in ways that may be instructive to the societal debate on
      health care reform.

PMID- 7710463
TI  - Does rhinoplasty make the nose more susceptible to fracture?
AB  - This study was conducted to investigate the vulnerability of the nasal bones
      following rhinoplasty. The incidence of nasal bone fracture in the general
      population was reviewed from the data available from the National Center for
      Health Statistics (NCHS). The NCHS report indicates an average of 51,200 nasal
      bone fractures each year for an average yearly population of 239,328,200 over a 5
      year period for the United States, producing an average rate of 0.021 percent per
      year. The history of 1121 patients who had undergone routine rhinoplasty or
      septorhinoplasty on an elective basis was then investigated for possible
      fractures following rhinoplasty. Of this group, 24 patients (16 females and 8
      males) sustained a total of 28 nasal bone fractures following rhinoplasty over a
      mean follow-up period of 4 years. This yields an actual or crude rate of 0.624
      percent per year, as compared with the age-standardized rate of 0.485 percent,
      according to the indirect adjustment method. The time interval between the first
      nasal procedure and subsequent fracture varied greatly, spanning from 1 month to
      6 years. The average time interval between the first nasal procedure and the
      subsequent fracture for 16 patients was less than 1 year. Over 70 percent of the
      patient population (n = 17) who sustained post-rhinoplasty fracture were under 30
      years old at the time of the fracture. On the basis of the study, it was
      concluded that the incidence of nasal bone fracture following rhinoplasty (0.624
      percent actual and 0.485 percent adjusted) is higher than that of fracture in the
      general population (0.021 percent) (p < 0.001).

PMID- 7710464
TI  - Prevalence odds ratio v prevalence ratio.

PMID- 7710465
TI  - Grammatical morpheme acquisition in 4-year-olds with normal, impaired, and late
      developing language.
AB  - The production of the grammatical morphemes studied by Brown and his colleagues
      was examined in free speech samples from a cohort of 4-year-olds with a history
      of slow expressive language development (SELD) and a control group of normal
      speakers. Results suggest that children with SELD acquire morphemes in an order
      very similar to that shown in previous acquisition research. Children who were
      slow to begin talking at age 2 and who continued to evidence delayed expressive
      language development by age 4 showed mastery of the four earliest acquired
      grammatical morphemes, as would be expected, based on their MLUs, which fell at
      Early Stage IV. Four-year-olds with normal language histories produced all but
      one of the grammatical morphemes with more than 90% accuracy, as would be
      expected based on their late Stage V MLUs. Children who were slow to acquire
      expressive language as toddlers, but who "caught up" in terms of sentence length
      by age 4 did not differ in MLU from their peers with normal language histories.
      However, they had acquired fewer of the grammatical morphemes. The implications
      of these findings for understanding the phenomenon of slow expressive language
      development are discussed.

PMID- 7710466
TI  - Metachronous torsion of the appendix testis.

PMID- 7710467
TI  - A clinical trial of induction of labor versus expectant management in postterm
      pregnancy. The National Institute of Child Health and Human Development Network
      of Maternal-Fetal Medicine Units.
AB  - OBJECTIVE: Management of the uncomplicated pregnancy prolonged beyond the
      estimated date of confinement is controversial, particularly when the cervix is
      unfavorable for induction. The benefit of reducing potential fetal risk with
      induction of labor must be balanced against the morbidity associated with this
      procedure. The objective of this study was to compare two strategies for managing
      postterm pregnancy (i.e., immediate induction and expectant management). STUDY
      DESIGN: Four hundred forty patients with uncomplicated pregnancies at 41 weeks'
      gestation were randomized to either immediate induction of labor (n = 265) or
      expectant management (n = 175). Patients with expectant management underwent
      nonstress testing and amniotic fluid volume assessment twice per week. Patients
      in the induction group underwent induction within 24 hours of randomization. To
      evaluate the efficacy of intracervical prostaglandin E2 gel, patients in the
      induction group were randomized in a 2:1 scheme to receive either 0.5 mg
      prostaglandin E2 gel or placebo gel intracervically 12 hours before induction of
      labor with oxytocin. RESULTS: The incidence of adverse perinatal outcome
      (neonatal seizures, intracranial hemorrhage, the need for mechanical ventilation,
      or nerve injury) was 1.5% in the induction group and 1% in the expectant
      management group (p > 0.05). There were no fetal deaths in either group. There
      were no differences in mean birth weight or the frequency of macrosomia (birth
      weight > or = 4000 gm) between the two groups (p > 0.05). Regardless of parity,
      prostaglandin E2 intracervical gel was not more effective than placebo in
      ripening the cervix. The cesarean delivery rate was not significantly different
      in the expectant (18%), prostaglandin E2 gel (23%), or placebo gel (18%) groups.
      CONCLUSIONS: Adverse perinatal outcome in otherwise uncomplicated pregnancies of
      > or = 41 weeks is very low with either of the management schemes described. Thus
      from the perspective of perinatal morbidity or mortality either management scheme
      is acceptable.

PMID- 7710468
TI  - Selection for transplantation.

PMID- 7710469
TI  - The medical appropriateness of tympanostomy tubes proposed for children younger
      than 16 years in the United States.
AB  - OBJECTIVE: To describe the clinical reasons tympanostomy tubes are proposed for
      children and to assess their appropriateness. DESIGN: Analysis of data previously
      collected prospectively by a national utilization review (UR) firm during a two
      step UR process to assess the medical appropriateness of tympanostomy tube
      placement. Nurses interviewed otolaryngologists' and primary care physicians'
      office staff to collect clinical data. For a randomly selected subsample of cases
      found inappropriate, we reviewed subsequent interviews of the otolaryngologists
      by physician reviewers, who looked for possible extenuating clinical
      circumstances or additional clinical data that might have changed the
      appropriateness category. SETTING: Otolaryngologists' practices from 49 states
      and the District of Columbia. PATIENTS: All 6611 children younger than 16 years
      who were insured by three clients of the UR firm and whose proposal to receive
      tympanostomy tubes were reviewed by this system from January 1, 1990, through
      July 31, 1991. The insurance companies in the study insured 5.6 million Americans
      at the time of the study. MAIN OUTCOME MEASURE: The medical appropriateness of
      tympanostomy tube surgery according to explicit criteria developed by an expert
      panel using the RAND/University of California-Los Angeles modified Delphi method.
      RESULTS: A total of 6429 (97%) of the cases were proposed for recurrent acute
      otitis media, otitis media with effusion, or both. Making generous clinical
      assumptions, 41% of the proposals for these reasons had appropriate indications,
      32% had equivocal indications, and 27% had inappropriate ones. Considering the
      additional information available from the subsample review, the proportion
      appropriate was 42%, equivocal 35%, and inappropriate 23%. CONCLUSION: About one
      quarter of tympanostomy tube insertions for children in this study were proposed
      for inappropriate indications and another third for equivocal ones.

PMID- 7710470
TI  - Interventional techniques in the management of disorders of the brain: current
      status.
AB  - The role, techniques and tools of interventional neuroradiology are growing
      rapidly because of the number of active investigators. Training programs are
      being certified by the American Society of Neuroradiology. Recommendations are
      that Interventional Neuroradiologists be fully qualified in neuroradiology (two
      years) and have a one or two-year additional fellowship in interventional. The
      ideal interventionalist would also have some clinical neuroscience training.
      While these training requirements seem excessive on the surface one must
      recognize that with the overall drop in routine angiography that a longer
      exposure is necessary to acquire the prerequisite knowledge, skill and experience
      easily obtained in one year ten years ago. In fact there has been some pressure
      to place all of diagnostic neuroangiography in the hands of interventionalists.
      Endovascular approaches are the treatment of choice for: (1) cerebral vasospasm,
      (2) carotid cavernous fistulae, (3) vertebral artery origin stenosis, (4)
      subclavian artery stenosis, (5) innominate and left carotid origin stenosis, and
      (6) giant intracranial aneurysms. Endovascular treatment is developmental and
      should be restricted to centers performing formal trials in the treatment of: (1)
      cerebral arteriovenous malformations and (2) internal carotid artery and
      intracranial stenosis.

PMID- 7710471
TI  - Use of Marlex mesh in the repair of recurrent incisional hernia.
AB  - Recurrent incisional hernia remains a major problem for the general surgeon. The
      rate of recurrence of hernia repaired by primary closure using nylon sutures or
      with knitted monofilament polypropylene (Marlex) mesh was studied. A total of 102
      repairs were performed over a 19-year period. Marlex mesh was used in 49 cases
      and primary closure in 53. All except two patients were followed from 1 to 15
      (mean 7.6) years or to death. The incidence of recurrence was 8 per cent when
      Marlex was used and 25 per cent after primary closure. In both groups the
      majority of the recurrences were in the first 16 months after repair. The use of
      Marlex mesh should be considered in the management of recurrent incisional
      hernia.

PMID- 7710472
TI  - Pruritus as a symptom of hepatitis C.
AB  - Recent isolation, cloning, and sequencing of the hepatitis C genome, which has
      led to the development of an enzyme-linked immunosorbent assay, has produced
      increasing recognition of a hepatic disease that frequently leads to potentially
      lethal, chronic active hepatitis. We describe four patients who had pruritus or
      in whom pruritus developed as a consequence of hepatitis C. The symptom of
      pruritus should be added to a growing list of cutaneous manifestations of this
      newly recognized inflammatory viral hepatitis.

PMID- 7710473
TI  - Ischaemic heart disease and cholesterol. There's more to heart disease than
      cholesterol.

PMID- 7710474
TI  - Ischaemic heart disease and cholesterol. Cholesterol reduction effective in
      established disease...

PMID- 7710475
TI  - Invited commentary: in defense of ecologic studies for testing a linear-no
      threshold theory.

PMID- 7710476
TI  - Effect of the oyster fungus on glycaemia and cholesterolaemia in rats with
      insulin-dependent diabetes.
AB  - We have investigated the effect of a diet containing of 4% oyster fungus
      (Pleurotus ostreatus) and 0.1% cholesterol on glycaemia and hyperlipoproteinaemia
      in rats with insulin-dependent diabetes (streptozotocin 45 mg/kg). After two
      months, the rats with diabetes kept on the oyster fungus diet, had a
      significantly lower basal and postprandial glycaemia, the insulinaemia remained
      unchanged. The cholesterol concentration was decreased by more than 40%, the
      lipoprotein profile was upgraded by the decrease of the cholesterol in both the
      low density and very low density lipoproteins. The oyster fungus decreased the
      cholesterol accumulation in the liver and had no significant effects on the
      levels of serum and liver triacylglycerols.

PMID- 7710477
TI  - Beethoven's nephropathy and death.

PMID- 7710478
TI  - How does a protein fold?
AB  - The number of all possible conformations of a polypeptide chain is too large to
      be sampled exhaustively. Nevertheless, protein sequences do fold into unique
      native states in seconds (the Levinthal paradox). To determine how the Levinthal
      paradox is resolved, we use a lattice Monte Carlo model in which the global
      minimum (native state) is known. The necessary and sufficient condition for
      folding in this model is that the native state be a pronounced global minimum on
      the potential surface. This guarantees thermodynamic stability of the native
      state at a temperature where the chain does not get trapped in local minima.
      Folding starts by a rapid collapse from a random-coil state to a random semi
      compact globule. It then proceeds by a slow, rate-determining search through the
      semi-compact states to find a transition state from which the chain folds rapidly
      to the native state. The elements of the folding mechanism that lead to the
      resolution of the Levinthal paradox are the reduced number of conformations that
      need to be searched in the semi-compact globule (approximately 10(10) versus
      approximately 10(16) for the random coil) and the existence of many
      (approximately 10(3)) transition states. The results have evolutionary
      implications and suggest principles for the folding of real proteins.

PMID- 7710480
TI  - Death of a tooth after rhinoplasty.

PMID- 7710479
TI  - Alpha-mannosidase: a rapid test for identification of Arcanobacterium
      haemolyticum.
AB  - A 4-h alpha-mannosidase test for identification of Arcanobacterium haemolyticum
      strains (n = 139) and differentiation of A. haemolyticum from Actinomyces
      pyogenes strains (n = 30) and other gram-positive rods was evaluated. Practically
      all A. haemolyticum strains (138 of 139) and the Listeria monocytogenes type
      strain were alpha-mannosidase positive, while all A. pyogenes strains and
      Corynebacterium (n = .25) strains as well as the Rhodococcus equi and
      Erysipelothrix rhusiopathiae type strains were negative. The rapid alpha
      mannosidase test, in conjunction with a Gram stain and catalase and reverse CAMP
      tests, was useful in identification of A. haemolyticum and in differentiation of
      A. haemolyticum from A. pyogenes and Corynebacterium spp.

PMID- 7710481
TI  - The negative tuberculin test. Tuberculin, HIV, and anergy panels.

PMID- 7710482
TI  - Antenatal formula advertising: another potential threat to breast-feeding.

PMID- 7710483
TI  - Re: Guns and self-protection (March 1994)

PMID- 7710484
TI  - The importance of using the nondominant hand in subclavian vein puncture.

PMID- 7710485
TI  - Chemical peel--what's in the formula?

PMID- 7710486
TI  - Viral contacts confound studies of childhood leukemia and high-voltage
      transmission lines.
AB  - Studies of childhood leukemia have reported a link with residential proximity to
      electric utility facilities. This paper elaborates on the hypothesis that
      residential proximity to electric utility transmission-systems is a surrogate for
      viral contacts, a potential confounder in these studies. While the causal
      implications of increased viral contacts is not established, the assumption made
      here is that a significant component of childhood leukemia has an infectious
      etiology. Increased viral contacts can result from residential mobility, being
      first born, or use of community childcare facilities. Re-analysis of existing
      studies should look specifically for the interaction between childhood leukemia,
      markers for viral contacts (e.g., residential mobility, birth order, use of
      outside childcare facilities), and residential proximity to high-voltage
      transmission lines. New study designs should include parameters to test directly
      for a virus-related infectious model for childhood leukemia.

PMID- 7710487
TI  - Performance on the National Board of Medical Examiners. Part I Examination by men
      and women of different race and ethnicity.
AB  - OBJECTIVE: To investigate the performance of men and women from various racial
      and ethnic backgrounds on the National Board of Medical Examiners Part I
      examination, controlling for any differences in measures of educational
      background and academic performance before entering medical school. DESIGN: A
      retrospective analysis of existing records from the National Board of Medical
      Examiners and the Association of American Medical Colleges. SETTING: National
      Board of Medical Examiners. PARTICIPANTS: All students taking the June
      administration of Part I for the first time in 1986, 1987, or 1988 and who were 2
      years from graduation from an accredited medical school. METHODS: Multiple
      regression methods were used to estimate Part I examination group differences in
      performance that would be expected if all students entered medical school with
      similar Medical College Admission Test scores, undergraduate grade point
      averages, and other prematriculation measures. MAIN OUTCOME MEASURE: Performance
      on the Part I examination. RESULTS: There were substantial differences in
      performance, with white students scoring highest, followed by Asian/Pacific
      Islanders, Hispanics, and blacks; within all racial and ethnic categories, women
      scored lower than men. Controlling for dissimilarities in academic background
      greatly reduced Part I differences among most racial and ethnic groups, except
      Asian/Pacific Islander men; unexplained differences remained between men and
      women. Results were consistent for the 3 years examined. CONCLUSIONS: The results
      of this study do not imply that physician performance varies among racial and
      ethnic groups or between men and women; no written examination can measure all
      the abilities that may be desirable to assess. Validity research investigating
      reasons for the reported gender and racial and ethnic differences in performance
      on the National Board examinations should be continued.

PMID- 7710488
TI  - Active immunization against hepatitis B infection of a haemodialysis population.
AB  - BACKGROUND: Patients undergoing haemodialysis run a high risk of developing
      hepatitis B virus infection. We noted high prevalence rates of this infection in
      our patients despite a policy of using active hepatitis B vaccination. We,
      therefore, examined the reasons why haemodialysis-associated hepatitis B virus
      infection was difficult to control. METHODS: We analysed retrospectively 131
      patients who had undergone haemodialysis for end-stage renal disease at our
      centre between June 1991 and May 1992. Patients given hepatitis B vaccine prior
      to starting haemodialysis were included in group A while those vaccinated after
      starting haemodialysis were placed in group B. The vaccination schedule consisted
      of 3 doses of recombinant hepatitis B vaccine given at monthly intervals.
      RESULTS: Fifteen patients had hepatitis B infection at entry, of whom 12 had had
      prior blood transfusions. Active immunization with recombinant hepatitis B
      vaccine was attempted in the remaining 116 patients. There were 16 patients in
      group A and 100 in group B. Of the 7 patients in group A and 46 in group B who
      completed the vaccination schedule, protective antibodies and markers of
      hepatitis B viral infection were noted in 3 and 2 patients respectively in group
      A and 7 and 14 patients respectively in group B. Vaccination was not completed in
      63 patients as 25 discontinued haemodialysis, 22 developed markers of hepatitis B
      infection and 16 underwent renal transplantation. CONCLUSIONS: Poor
      seroprotection rates with the standard vaccination schedule, unscreened blood
      transfusions and an inability to complete the vaccination schedule were the major
      reasons why active immunization against hepatitis B viral infection in our
      patients on haemodialysis has been largely unsuccessful.

PMID- 7710489
TI  - Medical ethics: an annotated bibliography.

PMID- 7710490
TI  - Renal cell carcinoma: prognostic factors.
AB  - OBJECTIVE: To establish the prognostic value of a series of pre-operative, per
      operative and histopathological parameters in relation to renal cell carcinoma
      (RCC). PATIENTS AND METHODS: This retrospective study involved a consecutive
      series of 76 patients (46 men and 30 women with a mean age of 65.3 years [range
      44-91]) with a histologically confirmed diagnosis of RCC. Patients who were
      admitted over the period 1980-1984 were included. Data such as erythrocyte
      sedimentation rate (ESR), alkaline phosphatase level, histological tumour grade,
      degree of necrosis and presence of tumour vessels were evaluated in relation to
      actuarial survival. RESULTS: The ESR and alkaline phosphatase level at the time
      of diagnosis of RCC, the histological tumour grade, degree of necrosis and
      presence of tumour vessels on angiography were all found to affect the actuarial
      length of survival significantly (P < or = 0.05 log-rank test). Macroscopic
      tumour demarcation estimated per-operatively by the surgeon or after surgery by
      the pathologist, microscopic demarcation, vascular density on histological
      examination, tumour diameter and vascular density on angiography were found not
      to affect actuarial survival significantly. CONCLUSION: The value of establishing
      simple and reliable diagnostic indicators for patients with RCC is stressed.

PMID- 7710491
TI  - Reversal of jejunoileal bypass in patients with morbid obesity.
AB  - Jejunoileal bypass for morbid obesity was performed on 182 patients between 1971
      and 1982. At 19 years' follow-up 60 (33 per cent) have had to undergo reversal.
      The compelling reasons for reversal were life-threatening malnutrition, immune
      complex disease, renal oxalate stones, osteomalacia and severe electrolyte
      disturbance. All patients gained weight after reversal of the jejunoileal bypass;
      most gained all the weight they had lost. Thirty-one patients returned to grade
      III obesity and 14 to grade II. Twelve patients had an associated vertical
      gastroplasty: ten regained their previous weight and only two stayed within
      normal weight. Patients were generally free from bypass-associated symptoms and
      complications apart from arthralgia and arthritis. This report concludes a series
      of articles published by the authors on jejunoileal bypass over the past 20 years
      describing the rise and fall of this surgical procedure.

PMID- 7710492
TI  - Immunization policies in Canadian medical schools.
AB  - OBJECTIVE: To determine the policies of Canadian medical schools concerning
      immunization of students and the methods used to promote these policies. DESIGN:
      Mail survey with the use of a 12-item, self-administered questionnaire; telephone
      follow-up to ensure response. SETTING: All 16 medical schools in Canada.
      PARTICIPANTS: Deans of Canada's 16 medical schools or their designates. All of
      them responded to the questionnaire. MAIN OUTCOME MEASURES: Policies on
      vaccination of students against diphtheria, hepatitis B, influenza, measles,
      mumps, poliomyelitis, rubella, tetanus and typhoid fever; recommended or required
      timing of such vaccination; methods for making students aware of immunization
      policies and for making vaccinations available to students; responsibility for
      payment for vaccination; compliance rates; methods used to monitor compliance;
      problems associated with noncompliance; policies for compensating students
      infected with hepatitis B or other vaccine-preventable diseases; and future plans
      for vaccination of medical students. RESULTS: Vaccination against rubella was
      required in 11 (69%) of the 16 medical schools, and vaccination against tetanus,
      diphtheria and hepatitis B was required in 10 (63%). Nine schools (56%) required
      vaccination against measles and poliomyelitis, and eight (50%) required mumps
      vaccination. Only three schools (19%) required or recommended influenza
      vaccination, and only one recommended vaccination against typhoid fever. The
      authors identified various methods used to promote student awareness of
      immunization policies, make vaccinations available, pay for vaccinations and
      monitor compliance. CONCLUSIONS: Each medical school has a unique set of
      requirements and recommendations for the vaccination of medical students.
      National guidelines on immunization for medical students and a comprehensive and
      nationally coordinated vaccination program would help to ensure that students
      receive proper protection from disease.

PMID- 7710493
TI  - Further comment on international referrals.

PMID- 7710494
TI  - Recurrent anterior shoulder instability.
AB  - The purpose of this study was to compare 2 radiographic methods for measuring
      anteversion and to determine whether glenoid anteversion is a significant factor
      in recurrence of instability after anterior repair. West Point axillary
      roentgenograms were obtained in 128 patients (138 shoulders) at a mean of 9 years
      after surgery. Two methods to measure glenoid anteversion were compared: The
      angle between the glenoid and the body of the scapula, and the angle between the
      glenoid and the posterior margin of the acromion. There was less variation in the
      measurements using the glenoid margin-posterior acromion angle. By this method,
      anteversion was 11 degrees +/- 4 degrees for the 15 patients with multiple (2 or
      more) recurrences, 8 degrees +/- 3 degrees for the 15 patients with 1 recurrence,
      and 6 degrees +/- 5 degrees for the 109 patients with no recurrences. Although
      these differences are statistically significant (P = 0.003), they probably are
      not clinically important because they are small (mean of only 5 degrees). The
      differences obtained by measuring the angle between the glenoid and the body of
      the scapula were not statistically significant.

PMID- 7710495
TI  - How many psychiatric beds?

PMID- 7710496
TI  - A personal technology transfer effort in DNA diagnostics.

PMID- 7710497
TI  - Needs not diagnosis: towards a more rational approach to community mental health
      resourcing in Britain.

PMID- 7710498
TI  - The advanced life support in obstetrics course. A national program to enhance
      obstetric emergency skills and to support maternity care practice.
AB  - Unexpected emergencies occur during routine maternity care. Perceived or actual
      deficiencies in training may decrease the quality of care and increase liability
      risks and anxiety among providers. This may lead the provider to discontinue
      obstetrics, which results in problems in access to care. To improve the training
      for obstetric emergency management, an Advanced Life Support in Obstetrics (ALSO)
      course was developed. This skill-enhancing course, modeled after other life
      support courses, is designed to improve the quality and availability of maternity
      care through standardized training in the management of emergencies and improved
      communication between maternity care providers. A total of 1315 physicians and
      nurses attended 35 ALSO courses from 1991 through 1993. Seventy-six percent were
      family physicians in practice; 20% were from rural areas. About 15% were in
      hospitals with no obstetricians or pediatricians on staff. Attendees reported a
      significant increase in their level of comfort in the management of obstetric
      emergencies and a greater intention to continue maternity care.

PMID- 7710499
TI  - Ocular manifestations of familial polyposis adenomatous coli.

PMID- 7710500
TI  - Histomorphometric and mineral density fractionation studies of lumbar vertebrae
      of intact and ovariectomized (OVX) monkeys.

PMID- 7710501
TI  - Lack of clarity in presenting statistical data.

PMID- 7710502
TI  - Extended wear, corneal hypoxia, and corneal ulcers.

PMID- 7710503
TI  - Myxoid cutaneous pleomorphic fibroma.

PMID- 7710505
TI  - Reamed vs non-reamed acetabula.

PMID- 7710504
TI  - Cutaneous manifestations of diabetes mellitus.

PMID- 7710506
TI  - Does rhinoplasty make the nose more susceptible to fracture?

PMID- 7710507
TI  - Missed diagnosis of colorectal carcinoma at barium enema examination.

PMID- 7710508
TI  - Laparoscopic colectomy.

PMID- 7710509
TI  - Increases in type III collagen gene expression and protein synthesis in patients
      with inguinal hernias.

PMID- 7710510
TI  - Transurethral resection of the prostate: monocular surgery under water.

PMID- 7710511
TI  - Drug-induced linear IgA bullous dermatosis.

PMID- 7710512
TI  - Normal bat flora.

PMID- 7710513
TI  - Are today's epidurals the 12% solution?

PMID- 7710514
TI  - Re: "Accepting the limits of ecologic studies: Drs. Greenland and Robins reply to
      Drs. Piantadosi and Cohen".

PMID- 7710515
TI  - Molecular genetic basis of Wilms' tumour?

PMID- 7710516
TI  - New optimism for pregnant HIV positive women.

PMID- 7710517
TI  - Childhood immunization availability in primary care practices.

PMID- 7710518
TI  - Cardiac tamponade secondary to giant lymph node hyperplasia. Castleman's disease.

PMID- 7710519
TI  - Pressure support ventilation.

PMID- 7710520
TI  - Corpus luteum defect--"alloyed gold standard".

PMID- 7710522
TI  - Performance on the NBME Part I examination.

PMID- 7710521
TI  - Response to HarPaz, Weiner, and Leszcz.

PMID- 7710523
TI  - Estrogen replacement therapy in breast cancer survivors.

PMID- 7710524
TI  - Effect of tacrine in Alzheimer's disease: or non-effect?

PMID- 7710525
TI  - Chrysotile, tremolite, and mesothelioma.

PMID- 7710526
TI  - Supplementary motor area activation preceding externally triggered movements.

PMID- 7710527
TI  - Capsular synovial metaplasia and breast implants.

PMID- 7710528
TI  - Immunology of AAU in AS patients.

PMID- 7710529
TI  - Transrectal Tru-cut biopsy of prostate using a protective sheath.

PMID- 7710530
TI  - Sleep and cardiac diseases amongst elderly people.

PMID- 7710531
TI  - The appropriateness of tympanostomy tubes for children.

PMID- 7710532
TI  - The appropriateness of tympanostomy tubes for children.

PMID- 7710533
TI  - Aortopulmonary paraganglioma, a rare tumor.

PMID- 7710534
TI  - Misinterpreting Aquinas.

PMID- 7710535
TI  - Cuban optic neuropathy.

PMID- 7710536
TI  - Children with persistent cough--outcome with treatment and role of Moraxella
      catarrhalis?
AB  - 52 children with severe cough persisting for more than 10 days were randomized to
      treatment with amoxycillin/clavulanic acid or placebo in a prospective double
      blinded study. Clinically suspected cases of pertussis were excluded, yet 12
      (23%) of the children had laboratory verified pertussis infection. The
      nasopharyngeal colonization showed a predominance of Moraxella catarrhalis which
      was isolated in 37 (71%) children. Streptococcus pneumoniae and Haemophilus
      influenzae were isolated in 11 (20%) and 16 (30%) children, respectively. The
      antibiotic-treated group had a significantly better recovery in both the
      pediatrician's estimation (p = 0.02) and the independent parental judgement (p =
      0.002). These findings are consistent with the view that Moraxella catarrhalis
      could be directly involved in the pathogenesis of persistent cough in children.

PMID- 7710537
TI  - Beta-thromboglobulin (beta tg) and platelet factor 4 (PF4) in patients with
      myeloproliferative diseases.

PMID- 7710538
TI  - Cyclosporin A is not very effective in erythema nodosum leprosum (ENL)

PMID- 7710539
TI  - Alternative views on the effects of recombinant interleukin-1-receptor
      antagonist.

PMID- 7710540
TI  - Re: The role of preserved autogenous cartilage graft in septorhinoplasty.

PMID- 7710541
TI  - Laparoscopic ileostomy and colostomy.

PMID- 7710542
TI  - In response to article by Mailis et al. "Alterations of the three-phase bone scan
      after sympathectomy".

PMID- 7710543
TI  - A couple of points in the IABP article.

PMID- 7710544
TI  - Medical involvement in torture.

PMID- 7710545
TI  - Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed
      epilepsy. UK Lamotrigine/Carbamazepine Monotherapy Trial Group.
AB  - Lamotrigine has been licensed widely as adjunctive therapy for partial and
      secondary generalised seizures. Use of the drug as monotherapy was investigated
      in a double-blind, randomised, parallel-group comparison with carbamazepine in
      newly diagnosed epilepsy. After 4 weeks of planned, fixed dose escalation, doses
      were adjusted according to efficacy, adverse events, and plasma concentrations.
      151 of 260 patients (131 lamotrigine, 129 carbamazepine) in eight UK centres
      completed the 48-week trial. No differences in efficacy between the drugs were
      found for partial seizures with or without secondary generalisation or for
      primary generalised tonic-clonic seizures. The proportion of patients maintained
      seizure-free during the last 24 weeks of treatment was almost the same in both
      groups (39% lamotrigine, 38% carbamazepine). More patients with primary
      generalised tonic-clonic seizures (47% both groups) than those presenting with a
      focal onset (35%, 37%) were fully controlled. Overall, fewer patients on
      lamotrigine than on carbamazepine withdrew because of adverse events (15 vs 27%).
      The commonest side-effect leading to withdrawal with either drug was rash (9%,
      13%). Sleepiness was less common in lamotrigine than in carbamazepine recipients
      (12 vs 22%, p < 0.05). More lamotrigine than carbamazepine recipients (65 vs 51%,
      p = 0.018) completed the study (hazard ratio 1.57 [95% CI 1.07-2.31]).
      Lamotrigine and carbamazepine showed similar efficacy against partial onset
      seizures and primary generalised tonic-clonic seizures in newly diagnosed
      epilepsy. Lamotrigine, however, was better tolerated.

PMID- 7710546
TI  - Knee-replacement surgery in the United States and Ontario.

PMID- 7710547
TI  - Treatment of acute lymphoblastic leukemia in a second remission.

PMID- 7710548
TI  - Surfactant therapy: more evidence of effectiveness.

PMID- 7710549
TI  - Treating asthma. Oxygen is the first drug to use in acute asthma.

PMID- 7710550
TI  - Homoeopathy for recurrent upper respiratory tract infections. No children
      received no treatment.

PMID- 7710551
TI  - Psychotic illness in ethnic groups. Biological factors should not be ignored.

PMID- 7710552
TI  - Determining the number of psychiatric beds needed.

PMID- 7710553
TI  - Out of hours care. Guidelines are needed on when to visit.

PMID- 7710554
TI  - Guidelines for choice of radiographic projections.

PMID- 7710555
TI  - Evaluation and treatment of "psychogenic" pruritus and self-excoriation.

PMID- 7710556
TI  - A further case of squamous cell carcinoma in the oral cavity of a squirrel
      monkey.

PMID- 7710557
TI  - Infection after face lift.

PMID- 7710558
TI  - A superior labial flap for repair of full-thickness alar defect.

PMID- 7710559
TI  - Recycling unused medical supplies.

PMID- 7710560
TI  - Effects of food deprivation and metabolic fuel utilization on the photoperiodic
      control of food intake in Siberian hamsters.
AB  - Unlike rats, Siberian hamsters exhibit seasonal changes in energy balance that
      are controlled by the photoperiod (daylength). In Siberian hamsters, body weight
      and fat, and food intake peak in long, summer-like days and reach nadirs in
      short, winter-like days. The purpose of the present experiments was to test
      whether metabolic challenges that increase food intake in laboratory rats also
      increase feeding in Siberian hamsters. Specifically, we asked the questions: (a)
      Is food intake increased following a fast?; (b) Is food intake increased
      following treatments that block metabolic fuel utilization, such as the glucose
      utilization blocker 2-deoxy-D-glucose (2 DG), or that enhance storage of
      metabolic fuels, such as short acting insulin (regular insulin)?; (c) Does the
      combination of food deprivation and decreased metabolic fuel utilization increase
      food intake?; and (c) Does the photoperiod affect the feeding and physiological
      responses to metabolic challenges? Food intake was measured in response to
      fasting, insulin or 2 DG treatment in adult female Siberian hamsters housed in
      long photoperiods. Following exposure to a short photoperiod, these hamsters were
      tested for their response to insulin and 2 DG, but not to fasting. Food intake
      did not increase following fasts of 12, 24, or 48 h. Food intake was increased in
      long day-housed hamsters given the lowest dose of 2 DG tested (125 mg/kg) 2, 4,
      and 6 h after treatment, but not in short days nor in long days with larger doses
      of the 2 DG. Similarly, food intake was increased by treatment with regular
      insulin in long days, but not short days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7710561
TI  - Effect of short term changes in blood glucose on visual pathway function in
      insulin dependent diabetes.
AB  - BACKGROUND: Visual pathway function is abnormal in patients with insulin
      dependent diabetes mellitus (IDDM) without retinopathy, yet the mechanism
      underlying this abnormality is unknown. It is hypothesised that short term
      changes in blood glucose level affect visual pathway function in IDDM. METHODS:
      Colour discrimination was measured in 10 uncomplicated aretinopathic IDDM
      patients during hyperinsulinaemic clamp, with the Farnsworth Munsell 100 hue test
      (100 hue test). After stable euglycaemia, patients were made hyperglycaemic (14
      mmol/l), maintained euglycaemic (5 mmol/l), and rendered hypoglycaemic (2.5
      mmol/l), in random order, on separate occasions at least 1 week apart. RESULTS:
      Short term (1-2 hours) changes in blood glucose did not affect colour
      discrimination: mean (SD) 100 hue error score at 2.5 mmol/l was 34 (22) compared
      with 35 (33) at 5 mmol/l, and 39 (28) at 14 mmol/l. CONCLUSION: These data
      suggest that short term (1-2 hours) changes in blood glucose are not the
      mechanism for visual pathway dysfunction in aretinopathic IDDM patients.

PMID- 7710562
TI  - Distribution of cholinergic neuron-specific gangliosides (GT1a alpha and GQ1b
      alpha) in the rat central nervous system.
AB  - A newly developed mouse monoclonal antibody, GGR-41, was used to localize a novel
      species of gangliosides, GT1a alpha and GQ1b alpha, in the rat central nervous
      system. Intense immunoreactivity was found in the neuropil of the spinal cord
      dorsal horn, spinal trigeminal nucleus, solitary tract nucleus, superior
      colliculus, interpeduncular nucleus, hypothalamus and septal area. The results
      suggest that GT1a alpha and GQ1b alpha are expressed in the nerve terminals of a
      certain population of cholinergic fibers.

PMID- 7710563
TI  - Three-month efficacy and safety of once-daily diltiazem in chronic stable angina
      pectoris.
AB  - The 3-month efficacy and safety of a once-daily controlled formulation of
      diltiazem (180 to 360 mg/day) were assessed in a study of 54 patients with angina
      pectoris. This multicenter study was a nonrandomized, placebo run-in, open-label,
      3-month trial followed by a 1-week, double-blind, randomized period during which
      most patients (89%) received placebo. There were only minimal changes in the time
      to termination (mean change +/- SEM -5.8 +/- 9.6 seconds), time to onset of
      angina (10.5 +/- 12.2 seconds), and the time to 1 mm ST-segment depression (2.9
      +/- 12.5 seconds) from the end of the titration phase to the end of the open
      label study. There were, however, statistically significant differences between
      the end of the 3-month treatment phase and the end of the 1-week randomized
      placebo phase for those 3 efficacy parameters (-37.3 +/- 11.2, -58.6 +/- 13.6,
      and -45.6 +/- 16.4 seconds, respectively). Diltiazem significantly decreased the
      frequency of anginal attacks and nitroglycerin use at the end of the 3-month
      treatment phase compared with results at the end of the randomized double-blind
      placebo phase. No new or unusual adverse events were reported during treatment.
      The present results suggest that there is no loss of efficacy of once-a-day
      diltiazem when administered for a long period to patients with chronic stable
      angina pectoris.

PMID- 7710564
TI  - Careers in academic general practice: problems, constraints, and opportunities.
AB  - Changing priorities in the NHS have underlined the crucial importance of academic
      general practice in providing quality training and research to underpin
      developments in general practice. Unfortunately, several problems and constraints
      mean that the full potential of general practitioners to make a contribution to
      teaching and research has not been realised. These issues are examined and
      recommendations for improvements are made. Obstacles to career development for
      academics in general practice should be removed. The funding of academic general
      practice should be the same as for other medical disciplines. Vocational training
      for general practice should be extended to include research and audit methods,
      particularly for doctors interested in an academic career. Above all, the long
      term objective should be to integrate undergraduate and post-graduate general
      practice to increase the overall effectiveness of teaching and research and hence
      the quality of service general practice.

PMID- 7710565
TI  - Maximal genetic potential for adult stature: is this aim desirable?
AB  - Current nutrition theory holds that maximization of human growth and stature is a
      desired anthropometric outcome. However, some evidence demonstrates that lower
      energy intakes may actually confer a degree of future protection against
      degenerative processes, particularly atherosclerosis and cancer.

PMID- 7710566
TI  - Maternal hemolysis, elevated liver enzymes, low platelet count, and neonatal
      outcome.
AB  - Pregnancies complicated by the syndrome of hemolysis, elevated liver enzymes, and
      low platelet count (HELLP) have been associated with both a poor maternal and a
      poor neonatal outcome in several publications. Because many studies were small
      and gave only scant information regarding the infants, we analyzed the clinical
      course of 89 neonates born to mothers with the HELLP syndrome. Ninety-eight
      percent of the neonates were born by cesarean section. Infants with a maternal
      HELLP syndrome were often small for gestational age (39%). The incidence of
      perinatal asphyxia was found to be 5.6%. Additionally, the affected very low
      birthweight (VLBW) infants had relatively high incidences of leukopenia (21%),
      neutropenia (33%), and thrombocytopenia (33%). Initially, 54% of the LBW infants
      were found to have normoblasts and 25% erythrocytosis. The incidence of these
      changes in blood cell count increased with decreasing birthweight. Nosocomial
      infections occurred more often in infants with a reduced neutrophil count. The
      overall mortality rate was 56 per 1000. Comparing the statistics of the VLBW
      infants with a maternal HELLP syndrome (n = 32) to all infants with a birthweight
      less than 1500 g (n = 521) during the investigational period, we found a similar
      mortality rate (9.3% and 8.4%, respectively). The pulmonary morbidity was also
      similar. The incidence of intracranial hemorrhage in VLBW infants with a maternal
      HELLP syndrome was lower (12.5% versus 18.2%) and of necrotizing enterocolitis
      was higher (6.2% versus 1.9%).

PMID- 7710567
TI  - Fetal renal artery and umbilical artery Doppler flow and fetal urine output.
AB  - The object of this study was to determine if a correlation exists between the
      resistance index (RI) of the umbilical artery, the RI of the fetal renal artery,
      and hourly urine output by fetuses of normal pregnancies. Doppler flow study of
      the fetal renal artery and the umbilical artery was performed in 110 fetuses
      between 19 and 40 weeks' gestation. Color and pulse wave Doppler was used to
      obtain the flow velocity waveforms. The RI of the flow velocity waveforms was
      calculated. Fetal bladder volume was calculated by transverse, anteroposterior,
      and longitudinal diameters obtained from coronal and transverse sonographic
      images of the fetal urinary bladder. The difference in bladder volume at 30
      minute intervals was used to determine hourly urine output. Gestational age has a
      positive linear association with fetal urine output (P < 0.01). The RI of the
      fetal renal artery has a negative linear association with gestational age (P <
      0.05). The RI of the umbilical artery decreased with an increase in gestation age
      (P < 0.01). There was a significant correlation between the RI of the umbilical
      artery (P < 0.01) and the fetal renal artery (P < 0.05) and hourly urine output
      by the fetus. The RI of the fetal renal artery decreased with gestational age.
      Hourly urine output of the fetus increased with gestational age. The RI of the
      umbilical artery and the fetal renal artery had a significant correlation with
      fetal urine output.

PMID- 7710568
TI  - Neonatal hepatitis and excessive hepatic iron deposition following intrauterine
      blood transfusion.
AB  - The management of hemolytic disease has undergone a number of significant changes
      over the past few decades. Intrauterine transfusion therapy, particularly
      intravascular transfusions, have significantly reduced the morbidity and
      mortality associated with isoimmunization. This therapy results not only in the
      transfusion of blood, but also in the transfusion of iron. The long-term
      consequences of iron loading in the fetus are unknown. We report a case of a
      newborn with Rh hemolytic disease who was treated with in utero transfusions and
      subsequently developed liver disease consistent with iron overload.

PMID- 7710569
TI  - Effects of single dose calcium gluconate infusion in hypocalcemic preterm
      infants.
AB  - We conducted a prospective, double-blind study of 43 preterm infants to examine
      the effect of a single calcium gluconate infusion as therapy for neonatal
      hypocalcemia on serum calcium concentrations and hypocalcemic signs in preterm
      infants with low total serum calcium concentrations. Total and ionized serum
      calcium was measured and signs of irritability, jitteriness, and twitching were
      scored (scale 0-9) by blinded observers before and after receiving one dose of
      either calcium gluconate (100 mg/kg) or placebo (normal saline). Total and
      ionized serum calcium increased 3 to 6 hours following the calcium, but not the
      placebo, infusion. Of the infants with hypocalcemic signs, the average score of
      hypocalcemic signs decreased in the 11 calcium-treated infants; the 12 infants
      with hypocalcemic signs showed no change of hypocalcemic signs following
      treatment with placebo. We conclude from this study that a single dose of calcium
      gluconate (100 mg/kg) in hypocalcemic preterm infants raise total and ionized
      serum calcium and decrease clinical signs of hypocalcemia.

PMID- 7710570
TI  - Erythropoietin use in pregnancy: two cases and a review of the literature.
AB  - End-stage renal disease complicates only a small percentage of pregnancies, but,
      of these, virtually all become anemic due to a deficiency in erythropoietin.
      Erythropoietin has been shown to correct anemia due to renal disease in
      nonpregnant patients. We report two cases of erythropoietin use during pregnancy
      complicated by severe anemia due to renal failure. No maternal or fetal side
      effects were noted. Our two cases exemplify that erythropoietin is an effective
      means of treating anemia due to renal disease in the gravid patient.

PMID- 7710571
TI  - Perinatally acquired Pseudomonas infection: a newly recognized maternal risk
      factor.
AB  - Pseudomonas aeruginosa is a less common but, nonetheless, serious bacterial
      pathogen implicated in early-onset neonatal sepsis. This report demonstrates
      perinatal transmission from a mother with a long smoking history who had an oral
      abscess surgically drained prior to delivery and never received antibiotic
      therapy. This case emphasizes the need to consider prophylactic antibiotic
      coverage in similar patients to prevent the morbidity and mortality associated
      with this type of perinatally acquired infection.

PMID- 7710572
TI  - Plasma thrombomodulin levels in women with systemic lupus erythematosus.
AB  - Thrombomodulin (TM), an endothelial cell membrane glycoprotein, is released into
      blood as a soluble TM antigen after inflammation or injury to endothelium.
      Systemic lupus erythematosus (SLE) is characterized by multisystem inflammation
      of vascular endothelium. The objective of this study is to determine the
      circulating TM levels in pregnant and nonpregnant SLE women and the correlation
      of plasma TM levels with variables used to assess SLE activity. We found that
      there were no significant differences in plasma TM levels among pregnant SLE,
      nonpregnant SLE, and normal pregnant patients. However, significantly higher
      plasma TM levels were found in some SLE women with active disease or
      preeclampsia.

PMID- 7710573
TI  - Lack of mandibular movement manifested by absent fetal swallowing: a possible
      factor in the pathogenesis of micrognathia.
AB  - This study was performed to assess the association of lack of mandibular movement
      as manifested by absent fetal swallowing and micrognathia in a nonrestrictive
      intrauterine environment. Over a 5-year period, 14 fetuses with sonographic
      findings of polyhydramnios (amniotic fluid index [AFI] more than 20 cm), absent
      mandibular movement, and a nonvisualized fetal stomach, all consistent with
      absent fetal swallowing, were followed. A group of 14 fetuses, each with
      polyhydramnios (AFI more than 20 cm), yet with sonographic detection of fetal
      swallowing, served as controls. All gravidas in both groups were normoglycemic
      throughout gestation. Subsequent mandibular development was assessed at delivery
      or autopsy. Analysis of the data revealed that in the study group, 12 of these
      infants were liveborn, and two were stillborn. Eleven of the liveborn infants had
      an early neonatal death. All 14 infants of the study group demonstrated
      micrognathia. None of the control infants (all of whom survived) had
      micrognathia. In conclusion, this study supports the concept that normal
      mandibular growth may depend on the presence of mandibular movement during
      intrauterine development.

PMID- 7710574
TI  - Neonatal neutropenia in low birthweight premature infants.
AB  - Neutropenia, as defined by common reference values, occurs often in neonates. Its
      incidence, causes, and clinical consequences have not been studied extensively in
      premature neonates. Of 208 consecutive infants with birthweight up to 2000 g, 121
      (58%) had neutropenia. Low gestational age and low birthweight correlated with
      the incidence of neutropenia. Less than half of the neutropenic episodes could be
      attributed to infections, the others were related to specific perinatal events
      and due to drug therapy or were of unknown cause. Neutropenia following treatment
      with certain antibiotics was the most common cause of neutropenia occurring after
      the second week of life. The high incidence of neutropenia in premature neonates
      raises questions about application of these reference ranges to low birthweight
      infants and suggests the need for new reference values.

PMID- 7710575
TI  - Comparative study of erythrocyte deformability in maternal and cord blood.
AB  - To elucidate the rheological difference in maternal and fetal blood by
      determining erythrocyte deformability, 20 pairs of mothers and newborns, and 20
      nonpregnant women were studied. Erythrocyte deformability was measured by means
      of an electron spin resonance method. Erythrocyte deformability was dependent on
      the hematocrit, and there was an optimal hematocrit value at which the
      deformation was maximal. The hematocrit at which the deformability was maximal
      showed a lower value (32 to 35%) in maternal blood; conversely, a higher value
      (47 to 50%) occurred in fetal blood than that (40 to 43%) in nonpregnant control
      women. When the hematocrit of the red blood cell suspension in dextran solution
      was adjusted to 40% (nonpregnant blood), 35% (maternal blood), and 50% (fetal
      blood), the deformability of fetal erythrocytes was significantly higher than
      maternal blood (P < 0.05), and its value was almost similar to that of
      nonpregnant control women. Based on our results, erythrocyte deformability of
      fetal blood is much higher compared with the maternal blood, suggesting the
      effective oxygen supply to the fetal tissues even in the circumstances of lower
      oxygen tension.

PMID- 7710576
TI  - Brachial plexus palsy involving the posterior shoulder at spontaneous vaginal
      delivery.
AB  - Brachial plexus injuries sustained at birth have most often been attributed to
      the maneuvers performed when attempting to relieve a shoulder dystocia or to
      deliver a breech vaginally. In the case now reported, the brachial plexus injury
      involved the posterior shoulder. As the delivery was spontaneous and without
      forceps or manual rotation, with delivery effected using only the McRobert's
      maneuver, it is hypothesized that maternal expulsive forces in conjunction with
      lodging of the posterior shoulder on the sacral promontory resulted in the
      injury.

PMID- 7710577
TI  - Contemporary context for early-onset group B streptococcal sepsis of the newborn.
AB  - We examined early-onset newborn group B streptococcal (GBS) infection among the
      population of a large obstetric center in western Canada for the contemporary
      period 1987 to 1992. Attack rates for "definite" (bacteremic) and "presumptive"
      (urine group B antigen positive with clinical evidence) GBS infections were 0.85
      and 0.90 per 1000. Ten GBS-associated stillbirths were recorded. Seven deaths
      occurred among bacteremic newborns (18.4%). Using definitions of Boyer and
      Gotoff, 87.2% of all mothers with infected newborns manifested at least one risk
      factor, and 69.8% of all febrile pregnancies with either definition of infected
      newborn and 61.9% of a subset of the same with bacteremic offspring had maternal
      temperature 38 degrees C or higher prior to delivery. For our population,
      recommendations for universal antepartum GBS screening and intrapartum
      prophylaxis must be discussed in the context of an existing low frequency of
      bacteremic disease and with the understanding that fever in pregnancy may be
      enough to warrant greater intervention that might further reduce the rate of
      infection.

PMID- 7710578
TI  - Prenatal diagnosis of moderate unilateral hydrocephalus subsequently not
      requiring neonatal decompression.
AB  - Prenatal diagnosis of unilateral hydrocephalus is unusual. In the past most such
      cases have been treated with neonatal shunting procedures. We present an unusual
      case in which moderate unilateral hydrocephalus was diagnosed prenatally at 30
      weeks' gestation. Despite prenatal and neonatal sonographic signs of both
      cortical thinning and mild displacement of midline intracranial structures,
      confirmed by computed tomography, neonatal shunting was not required. The
      findings and course in this unusual case suggest that infrequently some of the
      milder cases of idiopathic nonprogressive unilateral hydrocephalus discovered
      later in life may possibly represent late detection of this preexisting
      condition.

PMID- 7710579
TI  - Retention of percutaneous venous catheter in the newborn: a report of three
      cases.

PMID- 7710580
TI  - Effect of different phototherapy lights on incubator characteristics and dynamics
      under three modes of servocontrol.
AB  - Phototherapy is one of the most common therapeutic interventions in modern
      neonatal medicine. Analysis of physiological responses to phototherapy requires
      understanding the physical effects of incident light under different modes of
      environmental control. In this study, we tested the effect of initiation of
      phototherapy under laboratory conditions in a convective incubator maintained in
      three clinically used servocontrol modes. Under conditions of air servocontrol,
      the initiation of phototherapy resulted in an abrupt sustained increase in the
      surface temperature of an infant simulator (a blackened aluminum disc). In
      contrast, when the surface (skin) temperature was the controlled variable, there
      was a profound drop in the incubator air temperature. An algorithm that
      simultaneously controlled both the skin and the air temperatures showed
      intermediate effects. Under conditions of skin servocontrol, fluctuations in air
      and environmental temperatures were observed for a period of 3 hours before
      steady state was reached. These findings are most clearly demonstrated using
      phase plane plotting techniques. We conclude that wide, abrupt, and sustained
      changes in the thermal environment of an incubator occur after phototherapy is
      initiated. Such changes must be anticipated in physiological studies using
      phototherapy.

PMID- 7710581
TI  - Shoulder dystocia: could it be deduced from the labor partogram?
AB  - The study was undertaken to test the hypothesis that shoulder dystocia might be
      suspected and reliably identified from the labor partogram. A retrospective
      analysis of 52 consecutive patients with shoulder dystocia was performed. The 52
      controls were the next consecutive parturient matched for maternal age,
      gestational age at delivery, parity, presentation, and infants weight at
      delivery. The mean dilation rate was 2.1 +/- 1.9 cm/hr in shoulder dystocia group
      compared to 2.4 +/- 1.5 cm/hr in the control group. The incidence of protracted
      rate of less than 1 cm/hr was 14.3% in shoulder dystocia group and 13.5% in the
      control group. The mean duration of second stage was 38.3 +/- 30.7 minutes in the
      shoulder dystocia group compared to 35.5 +/- 32.5 minutes in the control group.
      Only 1.9% have had a prolonged second stage (more than 2 hours) in the shoulder
      dystocia group compared to 1.9% in the control group. The difference between the
      groups regarding the length of labor was not statistically significant. We
      conclude that protracted labor does not seem to be a risk factor for shoulder
      dystocia.

PMID- 7710582
TI  - Influence of spontaneous or induced labor on delivering the macrosomic fetus.
AB  - Fetal macrosomia is a known intrapartum risk factor for fetal injury and maternal
      morbidity. The purpose of this study was to review our experience with macrosomic
      fetuses in nondiabetic pregnancies and compare perinatal outcomes between those
      whose labor had been spontaneous or induced. Between January 1989 and December
      1991, the 186 pregnancies of infants with birthweights greater than 4000 g (4001
      to 5131 g) underwent labor that had been induced (46) or spontaneous (140).
      Cesarean delivery was more common after induced than spontaneous labor (11
      [23.9%] vs 14 [10.0%]; P < 0.03) regardless of parity or gestational age.
      Frequencies of shoulder dystocia, 1-minute Apgar scores less than 7, and abnormal
      umbilical blood gas determinations were not different between the two groups. We
      conclude that spontaneous rather than induced labor is associated with a lower
      chance of cesarean delivery among those fetuses with birthweights 4000 g or more.

PMID- 7710583
TI  - Quasistatic volume-pressure curve to predict the effects of positive end
      expiratory pressure on lung mechanics and gas exchange in neonates ventilated for
      respiratory distress syndrome.
AB  - The shape of the volume-pressure (V/P) curve indicates alveolar collapse if it is
      convex to the pressure axis and indicates overdistension if it is concave.
      Positive end-expiratory pressure (PEEP) should either improve or decrease
      compliance and oxygenation in neonates ventilated for respiratory distress
      syndrome (RDS), depending on predominance of either alveolar collapse or
      overdistension. To test this hypothesis, we determined quasistatic V/P curves in
      13 preterm neonates and characterized their shape by an alveolar distension index
      (ADI) at PEEP levels of 2, 4, and 6 cm H2O. We calculated the ADI dividing the
      V/P ratio at a low tidal volume by the V/P ratio at a high tidal volume. This ADI
      was then related to the effect of PEEP changes on respiratory compliance and
      alveolar to arterial oxygen tension difference (AaDO2). ADI was assumed to
      indicate alveolar collapse if less than 1 and overdistension if more than 1. An
      increased PEEP in neonates with alveolar collapse (ADI less than 1) decreased
      AaDO2 more (12 vs 10 mm Hg/cm PEEP, not significant) and decreased compliance
      less (3 vs 17%/cm PEEP; P < 0.05) than in those neonates with alveolar
      overdistension (ADI more than 1). Conversely, a decreased PEEP in neonates with
      alveolar overdistension increased compliance more (19 vs 5%; not significant) and
      increased AaDO2 less (7 vs 26 mm Hg; P < .01) than in those with alveolar
      collapse. AaDO2 and compliance changes after PEEP alterations were significantly
      correlated to the ADI before PEEP alterations (P < 0.001).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7710585
TI  - Proceedings of the Nordic conference on snowmobile. Rovaniemi, March 22-23, 1994.

PMID- 7710584
TI  - Intravenous magnesium sulfate for premature labor: comparison between twin and
      singleton gestations.
AB  - Premature labor occurs frequently in twin gestations, and intravenous magnesium
      sulfate is commonly prescribed for tocolysis. The purpose of the present
      investigation was to determine the efficacy and safety of intravenous magnesium
      sulfate tocolysis in twin gestations using dosing regimens reported for
      singletons. Outcomes were compared between cases of singleton gestations eligible
      for tocolysis and admitted immediately before and after each twin case. The
      standard loading dose in both groups was 4 to 6 g intravenously with a
      maintenance dose of 1 to 3 g/hr. Data were compared using unpaired t tests or chi
      square analysis where appropriate. The 24 evaluable cases of twins were similar
      in demographics to a similar cohort of 48 singletons. Frequencies of side effects
      and durations of therapy were the same between the two groups. The number of days
      from beginning therapy until delivery was highly variable but not significantly
      different for the twin and singleton groups (13.5 +/- 14.8 vs 20.9 +/- 20.1 days,
      mean +/- SD). No significant differences were found between the twin and
      singleton groups in delays in delivery during the first 72 hours (16 [66.7%] vs
      35 [72.9%]) and by the 33rd completed week (10 [41.6%] vs 25 [52.1%]). In
      conclusion, guidelines for prescribing intravenous magnesium sulfate to inhibit
      premature labor in singletons are equally safe and effective for twin gestations.

PMID- 7710586
TI  - Thermal responses in the body during snowmobile driving.
AB  - Thermal responses were examined in 12 healthy men during snowmobile driving
      (tests for 1 1/2-2 1/2 hours) in mild winter conditions. Ambient temperature
      ranged from -1 to -13 degrees C and average wind chill index from 1,050 to 1,520
      kcal*m2/h. The subjects (23-49 years old) wore their ordinary winter clothing
      (insulation 1.7 - 2.4 clo). Work rate during the driving was 280-350 W. Rectal
      temperature increased slightly during driving, and mean skin temperature
      decreased quickly and fluctuated afterwards at a level 2-3 degrees C lower. Mean
      body temperature decreased by 1.2 degrees C in the most extreme case. Local
      cooling on the face and on the peripheral area of the extremities was considered
      the most serious problem: those temperatures were often below the limit of
      performance degradation and indicated occasionally the risk of frostbite. The
      winter conditions were mild in the present study, and on colder days cooling
      problems will be more severe, as the high incidence of frost injuries reported
      earlier indicates.

PMID- 7710587
TI  - Hand-arm vibration in snowmobile drivers.
AB  - Hand-arm vibration was measured on the handlebars of snowmobiles (N = 29) and a
      postal inquiry was made among reindeer herders, N = 2,705. Since many subjects
      had used also other vibrating tools a snowmobile group proper (N = 334) was
      established, and in this group 18% of the subjects reported that they had
      experienced white finger attacks and 48% numbness of the hands. The age-adjusted
      prevalence of the white finger syndrome was more than three times higher in the
      snowmobile group than in the controls. The frequency-weighted acceleration of
      snowmobile vibration was 3.5 m/s2, and risk evaluation based on the annex of the
      ISO 5349 standard predicted the prevalence of the white finger syndrome well in
      the snowmobile group. The most critical points for damping the vibration were the
      motor mounting and resonance in the steering yoke. There is a need for health
      care, technical improvements, changes in working habits and other protection
      means to reduce the symptoms of vibration associated with driving terrain
      vehicles.

PMID- 7710588
TI  - Whole body vibration and the snowmobile.
AB  - The whole body vibration from the seat and foot board was measured during ten
      years from 11 different snowmobiles to evaluate the exposure and the need for
      technical improvements. In a questionnaire more than half of the drivers had back
      pains but only a few of them considered the whole body vibration as a health
      hazard. However in the literature there is often comments on spinal injuries
      related to shock vibration. The frequency-weighted acceleration of snowmobile
      vibration was from 1 to 6.1 m/s2 and the risk evaluation using the ISO standard
      predicted the problems. Speed and the unevenness of the driving terrain caused
      vibration. The damping depends on the properties of the seat, terrain and speed
      limits. Also the driving posture is important. Especially on the snowmobile
      tracks the whole body vibration was high and according to modern knowledge more
      attention should be paid the technical properties of snowmobiles.

PMID- 7710589
TI  - Combined effects of cold, vibration and smoking, particularly in snowmobile
      users.
AB  - In a living and working environment more than one factor is usually important for
      physiological and psychological responses in the body. In this report the effects
      and combined effects of hand-arm vibration and cold, in particular their effect
      on frostbite, has been reviewed. As a second example is given the combined effect
      of vibration and smoking on vibration-induced white finger. In both cases our
      previous work among reindeer herders frequently using snowmobiles has been
      utilised as an example. Descriptive terms for combined effects have varied in
      previous multi-exposure studies. Here, the terminology recommended in the
      Saariselka agreement has been applied, and according to that the combined effect
      between cold and vibration on frostbite was called synergism and between
      vibration and smoking on white finger Bliss synergism.

PMID- 7710590
TI  - Noise and hearing loss in reindeer herders.
AB  - Air conduction hearing thresholds were examined in 512 reindeer herders (aged 18
      65 years, clinically normal ears) to evaluate the prevalence of noise-induced
      hearing loss. The hearing thresholds at 6 kHz showed significant noise-type
      impairment of hearing compared with those in the ISO 7029 standard or a Finnish
      reference population. The subjects were exposed to noise mainly in the use of
      snowmobiles and chain saws: daily noise exposure ranged from 93 to 104 dB(A). The
      age adjusted hearing thresholds deteriorated with the total noise exposure time,
      especially at 3 and 4 kHz. The prevalence of significant (class IV) hearing loss
      was 15% and impairment of hearing was frequently found even in the younger age
      groups. Although the use of ear protectors seems to be increased among reindeer
      herders, it still appears to be insufficient, and efforts to promote their use
      are needed.

PMID- 7710591
TI  - Snowmobile driving and symptoms of the locomotive organs.
AB  - The role of snowmobile driving as a factor in symptoms of the locomotive organs
      was examined in 1,793 reindeer herding men using a postal questionnaire. Thirty
      eight % of the respondents reported troubles in the upper limbs and shoulders
      which according to their own judgement were caused by snowmobile driving, and 34%
      reported such symptoms in the knees and 42% in the back. Aching, pain or
      tenderness upon movement in at least one joint during the current year, inquired
      by independent questions, were reported by 46% of the men. The prevalence of
      joint symptoms felt in the elbow (reported by 15% of the subjects), wrist (13%),
      fingers (10%), shoulder (22%) and knees (20%) increased by a factor of 1.6-2.5
      from those driving a snowmobile 1-20 days a year to those driving 150 days or
      more. The findings confirm earlier reports of increased occurrence of symptoms in
      the locomotive organs in snowmobile drivers and justify technical and other
      preventive measures.

PMID- 7710592
TI  - Ergonomic aspects on snowmobile driving.
AB  - From self-reported health surveys in Finland, Sweden and Norway we know that the
      reindeer herders have work related disorders. It is very likely that disorders
      such as lumbar back pain, neck and arm pain, knee pain and white finger syndrome
      are related to snowmobile driving. Our hypothesis was that driving postures,
      vibrations, impact from the driving surface and handling are the main reasons for
      the health problems, and that snowmobiles are not designed according to ergonomic
      principles. Our work started in the winter of 1993. We studied the general
      literature available on ergonomic postures, measurements of vibrations and body
      impact and we set out to explain the problems associated with driving and
      handling snowmobiles from a physiological, ergonomic and biomechanical point of
      view. At this point we identified some ergonomic requirements and requirements
      for the springing system of snowmobiles. We made static tests in which we watched
      the sitting position of the driver and tested the springing suspension. This was
      followed by a driving test and field observations of reindeer herders in 1994.
      The total load when driving comprises the load of the posture added with the load
      from vibrations and impact from the ground (3-10 G). The driving positions
      probably giving the most health problems are sitting with bent back,
      hyperlordotic neck, too high upper arms, more or less straight elbows and flexed
      and ulnar deviated wrist positions. The design of the snowmobile should enable
      the driver to sit with straight back, the hip joints at less than 90 degrees,
      knee joints at about 45 degrees, shoulder joints at 45 degrees, elbow joints
      around 60-70 degrees and the hand in a neutral position. The seat should be
      higher at the back and narrowed between knees. The height of the seat should be
      about 50 cm. The height of the steering-bar should be around 80 cm. The distance
      between the body of the driver and the steering-bar should be about 50 cm. Only
      one snowmobile was close to our requirements with a seat height of 48 cm and
      steering-bar height of 75 cm. The seat height varied with 10 cm, and the height
      of the steering-bar from 64 to 75 cm. The gas-bar should be placed on the
      thumbside so that it is possible to use the accelerator with the
      fingers.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7710593
TI  - Snowmobile traumas in Finnish Lapland: injuries to head, face and neck. Possible
      effects of speed and the use of helmet.
AB  - In a still continuing prospective study, the possible effects of the speed of the
      vehicle and/or the use of helmet on the incidence of injuries to the head, face
      and neck were studied. The present study population comprises 223 victims of
      snowmobile injuries transported to one of the three hospitals in Finnish Lapland
      since January 1, 1991. All information was acquired from the victim or relatives
      on admission. The speed of the vehicle on the occasion of the accident was
      reported to be < 40 kmph in 48%, 40-90 kmph in 44% and > or = 90 kmph in 8% of
      the cases. Use of a protective helmet was reported in 65% of the accidents.
      Trauma to the head, face and/or neck occurred in 33/223 accidents, i.e. 15%. The
      speed was in the two highest categories in eight of the nine cases with neck
      injuries; six patients were reported to have used a helmet. Injuries to the face
      seemed to occur at lower speed; 11 of the 13 injuries were in the two lower
      categories, while seven victims did not use a helmet. Head injuries occurred in
      11 cases with the speed poorly reported. A helmet was used by only four of the 11
      victims. In conclusion, the helmet seems to protect from head injury, but its
      effect seems controversial in neck injury. The reported helmet use is high in
      Finnish Lapland.

PMID- 7710594
TI  - Service of snowmobiles in the wilderness and villages.
AB  - The maintenance of terrain vehicles like snowmobiles has been developed for
      arctic wilderness use by paying attention to occupational health, safety and
      quality and efficiency of work. A small tent carried on a snowmobile sledge
      supplied with heating and lighting equipment was planned, built and tested. It
      was sized based on an ergonomic survey for the servicing of snowmobiles. The
      planned thermal and occupational aims were reached at temperatures down to -35
      degrees C. Two movable, shielded fluorescent lamps with total of 140 W electric
      power was enough to produce 150 lx illumination and the local illumination for
      the repair point was 700 lx. The 8 kW warm air fan had enough power to hold the
      temperature inside at the desired level with an outside temperature of -35
      degrees C. The fan was also used as a local heater by conducting warm air to the
      hands and tools. The temperature of the fingers was close to the comfort level,
      when repair work was carried in the tent. When the repair work was carried out
      outside, the finger temperature was near the risk of cold injury. The handles of
      the tools were made from heat insulating materials, which raised the contact skin
      temperature with about 3 degrees C.

PMID- 7710595
TI  - Developing the snowmobile helmet.
AB  - With the annually increasing use of snowmobiles in the Nordic countries the
      amount of accidents is also increasing. The head is the location of some of the
      most serious injuries with head injuries comprising 12% of all injuries. At the
      time being there is no special standard for the snowmobile helmet and there are
      mainly two kinds of helmet models on the market: full face and open face helmets.
      The most significant differences between the helmets were observed in the
      subjective evaluation, whereas the differences were minimal in technical
      evaluation. According to this study an open face helmet was more comfortable than
      a full face helmet. The present helmets have many deficiencies such as the lack
      of thermal comfort, high weight, slow removal of mist from the visor and
      unsatisfactory hearing protection. The aim of future development projects should
      be to make a more comfortable and lighter helmet. One important aspect of the
      project could be to integrate hearing protectors and an information channel in
      the helmet.

PMID- 7710596
TI  - Plasma fatty acid profiles of Canadian Inuit and Siberian Ganasan.
AB  - Cross-sectional data from 86 male and 59 female coastal Inuit of Igloolik (69
      degrees 40'N, 81 degrees W) showed a steep age-related increase in the percentage
      of plasma n-3 fatty acids, with parallel trends in 20:5 and 22:6 but not 18:3 n-3
      fatty acid concentrations. Omega-7 + 9 (p < .001) and omega-9 fatty acid
      concentrations (P < .001 in M, .008 in F) also decreased with age. A tundra-based
      Siberian indigenous population (30 male and 11 female nGanasan) had similar
      percentages of n-3 and n-6 fatty acids to the young Inuit, with little age
      related change in either measure. Correlation matrices for the Inuit men showed
      quite strong negative associations of n-3 fatty acid percentages with total
      triglycerides (r = .34, p < .001) and phosphatidylcholine/free cholesterol ratio
      (r = -.36, p < .001). In the Inuit women, n-3 percentages were strongly related
      to phosphatidylcholine/free cholesterol ratio (r = -.60, p < .001), but not to
      triglyceride readings. The phosphatidylcholine/free cholesterol ratio was also
      correlated with n-6 percentages (r = -.55, p < .001). In the nGanasan men,
      triglyceride levels were correlated with n-6 (r = -.35, p < .050), but the size
      of the female sample was insufficient to establish useful correlations. The
      present data suggest that as the younger coastal Inuit are abandoning their
      traditional country foods, plasma levels of n-3 fall. Reasons why n-3 fatty acid
      levels are negatively related to the plasma phosphatidyl choline/free cholesterol
      ratio merit further investigation.

PMID- 7710597
TI  - Puberty, pregnancy, and menopause: lifecycle acculturation in a Copper Inuit
      community.
AB  - In the past three decades Copper Inuit women have gone from a situation of family
      centered births in tents and snowhouses, to community births in government-run
      nursing stations to hospital births hundreds of miles from home. This process,
      which has been well documented by John O'Neil, Patricia Kaufert and others, is
      one aspect of the medical acculturation of the Canadian Inuit. The present work
      demonstrates how this medical acculturation has profoundly affected both the
      quality and the character of information flow between generations regarding all
      life cycle processes from bith to puberty to menopause. This paper examines the
      changes in the transmission of cultural information about life processes for 3
      generations of Inuit women in the Central Canadian Arctic village of Holman and
      will consider the historical and social roots of these changes. Among the
      findings of the authors is that both elderly and young women are relatively
      knowledgeable regarding issues related to reproductive health and are comfortable
      discussing these topics. Women in their middle years, however, appear to be less
      knowledgeable and often display discomfort with the subject.

PMID- 7710598
TI  - Malocclusion in Labrador Inuit youth: a psychosocial, dental and cephalometric
      evaluation.
AB  - Epidemiological studies of malocclusion of world populations have been previously
      limited to dental parameters. This cross-sectional study examined the prevalence
      of malocclusion in the dentitions of Inuit (Eskimo) youth aged between 5-22 years
      from Labrador, Canada, using psychosocial, dental and skeletal (radiographic)
      parameters. Data were obtained from two communities, Nain (population 1079) and
      Hopedale (population 534). About 82% (n = 363) of the Inuit youth and 50% (n =
      222) of their parents responded to the psychosocial questionnaires. In total, 78%
      (n = 348) of the Inuit youth were examined intraorally to determine the
      prevalence of malocclusion using the Treatment Priority Index (TPI), and 23% (n =
      100) had cephalometric radiographs taken using a portable cephalometer. The
      results indicated that 95% of the Labrador Inuit youth examined had some degree
      of malocclusion, 10-16% were aware of their occlusal disharmonies, 55-65% wanted
      to have their teeth straightened, and 5% were teased by others because of their
      malocclusions. In addition, 63% of the parents seemed to be aware of their
      child's occlusal problems and 70% wished their children to wear orthodontic
      appliances if they were needed. Prevalence and awareness to malocclusion were
      positively correlated. According to the TPI, 18% had "severely handicapping" and
      20% had "very severely handicapping" malocclusions. The TPI score increased with
      age from 5.25 in the young group to 8.05 in the older age group (mean 6.7). There
      were high prevalences of crowded anterior teeth, upper lingual posterior
      crossbites, and open or edge to edge bites. A prevalence of 35% Angle Class I,
      49% Angle Class II and 16% Angle Class III molar relationships were observed.
      Cephalometric analysis demonstrated a mean wits measurement of -2.0 mm, a mean
      ANB angle of 4.7, a mean lower face height of 68.3 mm, a mean interincisal angle
      of 125 degrees and a mean frankfort mandibular plane angle of 31.3 degrees. A
      need for orthodontic care and further education were clearly indicated and highly
      recommended.

PMID- 7710599
TI  - Cold-induced responses in the upper respiratory tract.
AB  - Recent investigations have shown that the prevalence of bronchial asthma is
      higher among skiers exposed to cold and dry air than among nonskiers. The upper
      airway passages are responsible for warming and humidifying the inhaled air.
      During exercise in cold and dry air, warming and humidifying of the inhaled air
      continues in the bronchial tree. Under these conditions both nasal and bronchial
      mucosa are cooled by inspiratory air and remain cooled throughout the respiratory
      cycle. The air which reaches the bronchoalveolar air space is at body temperature
      and fully saturated in all conditions. In this article we briefly review the
      studies carried out regarding the effects of cold air inhalation on the upper
      respiratory tract.

PMID- 7710600
TI  - Acute and chronic effects of winter swimming on LH, FSH, prolactin, growth
      hormone, TSH, cortisol, serum glucose and insulin.
AB  - The present investigation is based on a 2.5 months selbstversuch (self
      experiment) of the authors, between October 21 1992, and January 6 1993. 11
      healthy students, five females and six males, age 24 to 29 years, and their
      teachers underwent regular winter swimming at least once a week, for 2 to 10
      minutes, at the natural water temperature (6.8 degrees C (October 1992) to 2.0
      degrees C (January 1993)) in the southern Baltic Sea. Blood samples were drawn
      before and 30 and 60 minutes after the cold bath, both at the first and the last
      day of the swimming season. TSH increased from 0.96 mU/l to 1.42 mU/l (p < 0.01)
      in the untrained, and from 0.93 mU/l to 1.43 mU/l (p < 0.01) in the cold-trained
      persons, and decreased thereafter (p < 0.01). Similar changes occurred in
      cortisol serum concentrations, though psychological stress seemed to interfere
      with cold stress. Cortisol increased from 99 ng/ml to 133 ng/ml in the untrained,
      and from 101 ng/ml to 137 ng/ml (p < 0.05) in the cold-trained persons within 30
      minutes after cold water immersion, and decreased thereafter (p < 0.01). There
      were mild decreases in prolactin serum levels after cold stress, whereas FSH, LH
      and growth hormone remained unaltered. There was a mild initial elevation of
      serum glucose after cold stress (plus 12 mg/dl, (p < 0.01)) which disappeared
      after training. There were long term training effects besides the effects on
      glucose: Basal prolactin levels increased by almost the factor two, and insulin
      serum levels dropped by almost 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7710601
TI  - [Primary radiotherapy of nasopharyngeal carcinoma].
AB  - One hundred twenty-one patients treated for nasopharyngeal carcinoma with
      radiation therapy were analyzed; 85 were male, 36 were female. Twenty-one percent
      had tumour stage T0/T1; 32.5%, T2; 27.5%, T3; and 19%, T4. In 75% of the cases,
      the lymph nodes were involved. Twelve patients underwent a neck dissection.
      Histology showed squamous cell carcinoma in 38%, lymphoepitheloid carcinoma in
      41.4%, undifferentiated carcinoma in 19%, and adenocarcinoma in 2%. Beginning in
      1980, a modified radiation technique with large portals and an increase of the
      dose from 57.1 Gy to 61.5 Gy targe volume dose was used. Five year overall
      survival was 32.1%, recurrence-free survival, 30.7%; and local recurrence free
      survival, 45.8%. Age, sex, and T stage had no significant influence on survival.
      Multivariate analysis (Cox model) showed that involvement of the lymph nodes,
      histology, and the new irradiation technique with the higher total dose
      significantly influenced survival.

PMID- 7710602
TI  - [The value of MRT in primary extramedullary plasmacytoma involvement of the head
      neck area].
AB  - Six patients with a primary extramedullary plasmocytoma in the head and neck were
      examined using MR imaging. The morphological appearance of these lesions was
      described to support the radiologist in the differential diagnosis of this rare
      lesion. All tumours appeared as oval-shaped and sharply delineated without any
      signs of infiltration. After contrast media application a distinct central
      inhomogeneity could be proved in all cases. Furthermore, demoscopical, clinical
      and therapeutical problems were discussed based on the literature.

PMID- 7710603
TI  - [The Heermann modification of intranasal microsurgery in lacrimal duct stenoses].
AB  - The authors demonstrated Heermann's modification of intranasal microsurgery on
      the tearways. Since 1912 all intranasal lacrimal sac operations at the Krupp
      Hospital (up to 98 cases yearly) have been performed according to Randolph and
      West (1909). During the last 36 years our patients have been operated on in a
      semisitting-(Fowlers)-position with the help of the binocular microscope and with
      hypotensive anaesthesia. This technique of lacrimal sac surgery is demonstrated
      "step-by-step" with the removal of the medial wall of the lacrimal sac in
      abscesses or dacryoliths. In rare cases of a presaccal stenosis, a circular
      resection of the stenosis after J. Heermann (1989/1991) was done to leave the
      common duct open by the retraction of the scar. That is the reason why the
      insertion of plastic prostheses is rarely necessary (only in patients with
      congenital aplasia or extensive stenosis of the horizontal lacrimal duct). Funnel
      shaped prostheses of glass were developed in 1925 by J. Heermann sen., of steel
      1930 by H. Heermann and made by plastic material 1966 by J. Heermann. During a
      ten-year period (1976-1986) we evaluated 659 cases of intranasal microsurgery on
      the tearways. The use of plastic prosthesis was necessary in 17 cases. Including
      reoperations (first operation after Toti) satisfactory results were obtained in
      94% of all cases.

PMID- 7710604
TI  - [Olfactory evoked potentials and contingent negative variation in expert
      assessment of disordered sense of smell].
AB  - Normally, the sense of smell is assessed by means of traditional subjective tests
      (sniff test, gustatory smell test, and trigeminus test). When results are
      inconclusive, an objective smell test is indicated. Simultaneously registering
      olfactory evoked potentials (OEP) and contingent negative variation (CNV) permits
      evaluation of both odor perception and odor discrimination. We can even
      objectively assess the false olfactory sensations in parosmia patients who are
      unable to discriminate between different odors. In this study, the results of 59
      patients with olfactory disorders are presented. Head trauma and upper
      respiratory infections were the most common causes of the patients' complaints.
      In twelve cases, lack of cooperation and patient unrest prevented us from
      evaluating the data. In anosmia, the objective results agreed completely with the
      patient's subjective assessment. In hyposmia and parosmia, the results agreed
      with the patient's subjective assessment in most cases; here we were able to
      arrive at a more specific diagnosis in several cases. The objective smell test
      can be used to supplement subjective methods and thus provide more reliable
      assessment of olfactory disorders.

PMID- 7710605
TI  - [Sense of smell].
AB  - About two million Americans suffer from anosmia. Most result from nasal
      obstruction, head injuries, and viral infections. Brain disorders like epileptic
      seizures, tumours, and dementia can distort can distort the sense of smell.
      Anosmia adversely affects patient well-being. Patients cannot detect spoiled
      food, gas leakage, or dangerous smoke. They are unable to distinguish flavour and
      smell the springtime or the ocean. Many products as soaps, cat litter, toilet
      paper, etc. are perfumed because consumers will more readily buy a product that
      smells nice than one that has no smell at all. Historically, the importance of
      odors was very different. The ancient Romans loved exotic aromas during their
      banquets and orgies. In the Middle Ages the church did not like fragrances. The
      French revolution of 1789 brought a revolution of deodorization to Europe. Today,
      fragrance companies' increasing sales are an indication of the power of odor.

PMID- 7710606
TI  - [Damage to the sense of smell after nasal septum-plasty and bilateral Takashi
      turbinate capping?].

PMID- 7710607
TI  - [Neuropathologic findings in chronic epilepsy].
AB  - The surgical treatment of chronic epilepsies is increasing rapidly. A review of
      279 surgical specimens of patients with chronic pharmaco-resistant epilepsies
      from the University of Bonn Medical Centre revealed specific histopathological
      findings in 89% of all well-preserved specimens. The most frequent focal lesions
      were low-grade brain tumours such as gangliogliomas, pilocytic astrocytomas and
      dysembryoplastic neuroepithelial tumours. Other common findings were glioneuronal
      and vascular malformations and Ammon's horn sclerosis. This suggests that chronic
      intractable epilepsies are frequently caused by structural alterations.

PMID- 7710608
TI  - [More precise characterization of humoral immune reactivity to cartilage tissue
      in patients with resorption of cartilage transplants in the area of the head and
      neck].
AB  - The problems with repeated failure of cartilage grafting in reconstructive
      surgery are not yet resolved. Humoral immunoreactivity against chondrocytes as
      well as typical cartilage collagens type II, IX and XI was investigated in
      patients who showed resorptions and/or rejections of transplanted cartilage
      grafts. The presence of antibodies against isolated human chondrocytes was
      determined using an indirect immunofluorescence method, an enzyme-linked
      immunosorbent assay (ELISA) for chondrocytes and immunoblotting with chondrocyte
      cell membranes. Furthermore, an ELISA for collagens type II, IX and XI as well as
      immunoblotting with purified collagens type II and XI were used. The control
      groups consisted of patients with successful cartilage transplantation, patients
      suffering from rheumatoid arthritis and healthy persons. Patients with
      unsuccessful cartilage transplantation showed significantly elevated titres of
      antibodies against chondrocytes (p < 0.001) and collagens type IX and XI (p <
      0.001) compared to the control groups. In one patient with unsuccessful cartilage
      graft, we could also find a humoral reactivity against collagen type XI by
      immunoblotting. In contrast, no humoral immune reactivity was demonstrable
      against chondrocyte cell membranes by immunoblotting. In all examined patients
      fifty percent of patients with repeated resorptions or rejections of transplanted
      grafts showed antinuclear antibodies (ANA), demonstrating a possible but not yet
      declared autoimmune disease. These data confirm a humoral immunoreactivity
      against chondrocytes as well as against collagen which could be responsible for
      resorptions and/or rejections observed after cartilage graft.

PMID- 7710609
TI  - [Enzyme digestion of autologous cartilage transplants. New possibilities for
      vital cryopreservation?--Initial results].
AB  - The use of autologous cartilage grafts is one of the most common procedures in
      plastic surgery. Commonly used chemical preservation procedures of the cartilage
      for a second operation usually lead to the loss of vitality of the graft. In the
      past few years cryopreservation methods were used in the maintenance of the
      vitality of the autologous grafts, although these efforts yielded a low vitality
      of the grafts. It seems that the matrix of the grafts is mainly responsible for
      the unsuccessful cryopreservation of cartilage. In this work we tried to degrade
      the matrix of the cartilage grafts by partial enzymatic digestion with
      collagenase type II and hyaluronidase to facilitate the penetration of
      dimethylsulfoxide (DMSO). Cell vitality was assessed by trypan dye exclusion. We
      could demonstrate that it is possible to raise the permeability of the matrix by
      enzymatic digestion. Cryopreservation of the digested cartilage yielded a
      vitality of nearly 20%. Our results suggest that pretreatment of cartilage grafts
      with specific enzymes before preservation enable more successful vital
      cryopreservation.

PMID- 7710610
TI  - [Immunohistochemical studies of the neuroanatomy of the human turbinates:
      innervation pattern of seromucous glands].
AB  - Seromucous glands are among the main components of human nasal mucosa. To control
      the different physiological functions of these glands, a dense nerval network is
      necessary. The aim of this study was to demonstrate the general innervation of
      the seromucous glands in nasal mucosa. Tissue samples of inferior human
      turbinates were fixed and embedded in paraffin wax or frozen. Serial sections
      were performed and incubated with antibodies either to neuron-specific enolase
      (NSE) or S-100 protein. The ABC method was employed to demonstrate the
      immunacomplexes. The sections were counterstained with haemotoxylin. Either NSE
      and S-100 protein-immunoreactive nerve fibres were found around the acini, ducts
      and in the connective tissue of the glands. Furthermore, a dense network of fine
      nerve fibres was detected in the submucosal region. The localisation of neurons
      in nasal glands confirms the direct nerval control of the diverse glandular
      functions. Additionally, the sensitive subepithelial network of fine nerve fibres
      might be involved in the regulation of glandular secretion.

PMID- 7710611
TI  - [Photodynamic diagnosis and therapy of neoplasms of the facial skin after topical
      administration of 5-aminolevulinic acid].
AB  - Topical application of 5-aminolevulinic acid (5-ALA) is a useful instrument for
      photodynamic diagnosis and therapy of skin tumours. Diagnostic fluorescence
      imaging after laser light irradiation (410 nm) revealed a high, tumour-specific
      fluorescence even in tumour areas not apparent prior to this examination
      technique. This demonstrates the possibility of photodynamic diagnosis to detect
      skin tumours. In the therapeutic group 8 patients with 6 solar keratoses and 12
      basal cell carcinomas underwent laser light irradiation using a wavelength of 635
      nm (dosage 100 J/cm2) 6 hours after topical application of 5-ALA in W/O emulsion.
      2-12 hours after laser application we observed reddened tumour tissue with mild
      oedema, subsequently followed by a crust and epithelised within 4-6 weeks. 2
      months after PDT a complete response was observed for all solar keratoses and for
      10 of 12 basal cell carcinomas. Photodynamic therapy following topical
      application of 5-ALA may be an alternative treatment modality for skin tumours.

PMID- 7710612
TI  - [Sarcoma of the nose and paranasal sinuses].
AB  - Sarcomas of the head and neck are rare tumours accounting for less than 1% of all
      malignant neoplasms in this region. The prognosis of these tumours and the
      survival in adults (< 50% at 5 years) is directly related to histological tumour
      type, tumour size and the possibility of adequate tumour resection. In the
      present paper, the authors present the course of sarcomas with special reference
      to rhabdomyosarcoma and osteosarcoma in the nose and paranasal sinuses. Surgical
      resection with pathologically free margins represents the best modality of
      initial therapy. Additional adjuvant radiotherapy and/or chemotherapy have shown
      better survival rates in pediatric patients and, to some degree, also in adults.
      The purpose of future studies should be the development of new therapy protocols
      which could further elucidate the beneficial effects of adjuvant therapy in the
      treatment of sarcomas of the head and neck.

PMID- 7710613
TI  - [Malignant melanomas of the nasal cavity and paranasal sinuses].
AB  - Mucosal melanomas of the nose and paranasal sinuses are rate tumours (2.4-4% of
      all malignancies in this area) with a poor prognosis. The increasing number of
      cutaneous melanomas during the last decades gave rise to determine the occurrence
      of mucosal melanomas of the nose and paranasal sinuses in our department between
      1987-92. During this time, 6 patients with malignant melanoma of the nose and
      paranasal sinuses were seen in our department, representing 11% of all patients
      (55) with malignant tumours in this region. In five cases surgery was performed
      (with two patients receiving postoperative radiotherapy); one patient was treated
      primarily with irradiation. The mean survival time was only 19 months, which-
      from the authors' point of view--was mainly due to the extension of the tumours.
      The findings of this study might indicate an increase of malignant melanomas of
      the nose and paranasal sinuses; however, the number of patients is too small for
      a final statement on this matter.

PMID- 7710614
TI  - [Synovial cell sarcomas of the head- and neck area].
AB  - The synovial cell sarcoma is a malignant soft tissue tumour which mostly occurs
      associated with or in a large joint. To date, the histogenetic origin has been
      discussed controversially and there is still no agreement as to whether it arises
      from normal synovium of joints, tendon sheaths or bursae, specialised forms of
      mesenchymal tissue (arthrogenous mesenchyma) or ordinary connective tissue. The
      tumour rarely occurs in the head and neck region. Only about 76 cases world-wide
      have been described up to now. We report on a case of a 30-year old man with a
      synovial cell sarcoma of the temporomandibular joint and a case of a 70-year old
      man with a synovial cell sarcoma of the hypopharynx. In the first case, although
      all possible therapeutical efforts were made (radical operation, radiotherapy,
      chemotherapy), recurrence of the tumour occurred locally, as well as metastases
      in the lungs and bones. The patient died three and a half years after the initial
      diagnosis of the tumour. The second patient suffered multiple metastases in the
      lungs and bones one year after operation followed by chemotherapy. To the present
      time there is no general agreement on how to treat synovial cell sarcomas, but
      without doubt first of all radical surgical excision must be performed if
      possible. Additional radiation and/or multidrug chemotherapy may be useful in
      special cases. In our opinion every case of synovial cell sarcoma should be
      published because it is of importance to get to know new aspects and
      therapeutical possibilities of this rare disease.

PMID- 7710615
TI  - Identifying disagreement in ordinal ratings within a fixed panel of
      cytotechnologists.
AB  - In many clinical settings, a fixed number of raters screen specimens with more
      than two ordinal outcomes (for example, mild, moderate, severe). A design is
      proposed that facilitates the measurement of both interrater and intrarater
      agreement and associated trends. Design deficiencies are discussed, as are the
      propriety and interpretation of some common indices of reliability and
      reproducibility. The concepts are illustrated with data from cytopathologic
      ratings for sputum light microscopy.

PMID- 7710616
TI  - Nuclear morphometry in automatic biopsy and radical prostatectomy specimens of
      prostatic carcinoma. A comparison.
AB  - Nuclear shape analysis performed upon prostatectomy specimens of prostatic
      carcinoma distinguished individual patients with good and poor prognoses. In
      order to be useful for prognosis assessment preoperatively, nuclear morphometry
      must be measured on needle biopsy specimens. We compared nuclear morphometry on
      automatic biopsy and radical prostatectomy specimens in 20 patients with
      prostatic carcinoma. Nuclear size was smaller (paired Student t test, P < .0001)
      in biopsy specimens (perimeter 17.0 +/- SD 4.9 microns, area 29.9 +/- 6.6
      microns2) than in prostatectomy specimens (perimeter 24.6 +/- 4.4 microns, area
      48.2 +/- 8.7 microns2). Nuclear shape was more abnormal in automatic biopsy
      specimens (nuclear roundness factor 82.0 +/- 18.8, ellipticity 90.5 +/- 27.7)
      than in surgical specimens (nuclear roundness factor 43.5 +/- 8.8, ellipticity
      54.0 +/- 14.7) (P < .0001). Study of specimens obtained by automatic biopsy
      preoperatively and automatic biopsy of the prostatectomy specimens at various
      steps of processing revealed that nuclear swelling and rounding occurred after 2
      24 hours of formalin fixation. Automatic prostate biopsies may more accurately
      reflect true nuclear morphometry and should be studied for preoperative prognosis
      prediction in patients with clinically localized prostatic carcinoma.

PMID- 7710617
TI  - Pathology of the elastic tissue of the skin in Costello syndrome. An image
      analysis study using mathematical morphology.
AB  - Only nine cases of Costello syndrome have been described so far. No definitive
      pathologic abnormalities have been found on skin biopsies. We undertook a
      quantitative study of the elastic tissue of the skin in one case of Costello
      syndrome in order to obtain objective scores of area, fragmentation, branching
      and texture of the elastic tissue, comparing it to cutis laxa syndrome, Ehlers
      Danlos syndrome and normal skin. The results showed an increasing fragmentation
      score and loss of anastomosing points in elastic tissue in Costello syndrome and
      cutis laxa syndrome in relation to normal skin. Thus, we conclude that image
      analysis revealed, in Costello syndrome, a state of disorder akin to that of
      cutis laxa syndrome. Therefore, both syndromes might have a common pathogenesis
      as far as elastic tissue is concerned. However, other cases should be analyzed to
      validate our conclusions on statistical grounds.

PMID- 7710618
TI  - Novel application of image analysis to the detection of spongiform change.
AB  - Spongiform change is the characteristic neuropathologic abnormality within the
      brain in Creutzfeldt-Jakob disease, the most common human spongiform
      encephalopathy, but traditional methods of evaluating this abnormality are
      subjective and laborious. In order to overcome these difficulties, a quantitative
      method of assessment of spongiform change was devised and implemented using image
      analysis techniques. Successful validation of this system was performed by
      subjective and objective comparison with a neuropathologist's assessment. In a
      test-set of 50 microscopic images a strong positive rank correlation (Rs = 0.91)
      was established between the image analyzer and the neuropathologist. This system
      should facilitate large-scale analysis of different patterns of spongiform change
      in cases of human spongiform encephalopathy.

PMID- 7710619
TI  - Ploidy of 36 stromal tumors of the gastrointestinal tract. A comparative study
      with flow cytometry and image analysis.
AB  - DNA ploidy was investigated by flow cytometry (FC) and image analysis (IA) in
      paraffin-embedded tissue sections from 36 stromal tumors of the gastrointestinal
      tract. The results of both techniques were correlated with pathologic features of
      the tumors and survival. Ten (27.8%) tumors were aneuploid by FC and IA. Most of
      the diploid tumors were identified by both techniques, but FC appeared to be
      superior to tissue section IA for identification of aneuploid tumors (25% vs.
      13.8%). Aneuploidy by FC correlated with pathologic grade and mitotic index (P <
      .05), and a trend to short survival was also detected (P < .1). No similar
      correlation was found by IA. Enlargement and variation of nuclei may explain the
      discrepancy between FC and IA.

PMID- 7710620
TI  - The relationship of Periotest values, biomaterial, and torque to failure in adult
      baboons.
AB  - A quantitative measure of implant stability would be beneficial to decision
      making regarding the status of the bone anchorage around an implant. The
      Periotest device has been reported to provide such a measure, but the in vivo
      data are incomplete and inconclusive in support of this claim. The purpose of
      this study was to determine in an in vivo model the relationship between
      Periotest values (PTV), three different implant biomaterials, and torque to
      failure. A total of 79 screw-shape implants made of commericially pure titanium,
      titanium alloy, and HA-coated alloy were evaluated in the posterior maxillary and
      mandibular quadrants of six female baboons following healing for 3 to 4 months.
      At uncovering, the implants were tested with the Periotest device and torqued to
      failure using an electronic torque driver. Analysis of the PTV-biomaterial
      relationship revealed no significant difference among the implants based on the
      biomaterial (P = .7453). Analysis of PTV-torque revealed a significant
      relationship (P = .0117), however, the association between PTV and torque was not
      strong and does not explain 92% of the variation between the parameters (Pearson
      correlation .2823, R2 = .08).

PMID- 7710621
TI  - Precision attachment-retained removable partial dentures: Part 2. Long-term study
      of ball attachments.
AB  - Patients provided with 24 ball attachment-retained removable partial dentures
      were followed up to 23.5 years. The prosthetic treatment included fixed partial
      dentures in 8 arches, and combinations of crowns and splint bars in 16 arches.
      All ball attachment matrices were supplied with vertical occlusal stops in
      contact with the patrices. A nonresilient hinged coupling was established between
      fixed partial dentures and removable partial dentures. Seventeen arches had only
      two or three remaining teeth. A total of 66 abutments for fixed partial dentures
      were included, 30 of which were root canal treated and supplied with posts. No
      technical failures (loss of retention/cement failure, root or tooth fracture,
      metal framework fracture) with the fixed partial dentures were recorded. With the
      removable partial dentures, additional retention with clasps was introduced in 2
      of the dentures (in addition to 8 originally), 2 had to be remade after
      fractures, and 4 dentures were relined.

PMID- 7710622
TI  - A comparison of the marginal and internal adaptation of titanium and gold
      platinum-palladium metal ceramic crowns.
AB  - The marginal and internal adaptation of metal ceramic crowns fabricated by
      electrical discharge machining and conventional metal ceramic alloys were
      compared. The crowns were cemented using zinc phosphate cement, embedded in epoxy
      resin, and sectioned in two planes: diagonal and buccolingual. The crowns were
      then measured at nine sites. The results showed that there were no statistical
      differences between the external marginal opening of the titanium and the gold
      platinum-palladium crowns. The overall marginal discrepancies for the
      restorations in this study were 61 microns (+/- 34 microns) for the titanium
      metal ceramic crowns and 47 microns (+/- 17 microns) for the gold-platinum
      palladium metal ceramic crowns.

PMID- 7710623
TI  - Bone grafts and implants in the treatment of the severely resorbed maxillae: a 3
      year follow-up of the prosthetic restoration.
AB  - Thirty patients with severely resorbed maxillae were treated in a one-stage
      procedure using bone graft and implant placement. A horseshoe-shaped bone graft
      was taken from the iliac wing and fixed to the residual maxillary ridge using
      titanium implants, which supported the prostheses placed after a 6-month healing
      period. The material constituted two groups: a development group, the first 10
      patients; and a routine group, the following 20 patients. At the 3-year follow
      up, the implant survival was 87.5% and the prosthesis stability was 100% in the
      routine group. The probing depth did not change during the follow-up period,
      while the grafted region decreased in volume during the first postoperative year.
      The patients reported improved chewing ability and improved life quality. Very
      few technical and prosthodontic complications occurred.

PMID- 7710624
TI  - The effect of airborne particle abrasion on the dentin smear layer and dentin: an
      in vitro investigation.
AB  - This study investigated the effect of airborne particle abrasion on the exposed
      dentin surfaces of 40 extracted teeth. A Siroflow abrasion unit was used to treat
      four groups of ten specimens that were subjected to 5, 10, 20, and 40 seconds of
      abrasion respectively. Statistical analysis (Spearman Rank Order) showed a
      significant difference between all groups (P < .05) but not within groups (P >
      .05). Scanning electron micrographs showed smear layer removal as an immediate
      effect of air polishing. Application times of longer than 5 seconds showed
      obstruction of dentinal tubule openings, possibly a result of abrasive powder
      residue. It was concluded that airborne particle abrasion removes the smear
      layer, and the amount of dentin removed corresponded to the time of application.

PMID- 7710625
TI  - Color stability of resin cements after accelerated aging.
AB  - The color stability of both light- and dual-polymerized samples of three shades
      of three commercial resin cements was measured using a reflection
      spectrophotometer after accelerated aging over a period of 179 hours. Porcelite
      cement was the most color stable, followed by Optec and then 3M. The Optec and
      Porcelite cements changed color after accelerated aging, but with one exception
      the changes were not perceptible. Five of six 3M cements had perceptible color
      changes after accelerated aging, becoming darker and more yellow. The two lighter
      shades of Optec and 3M changed color more than the darker shade. Most differences
      between light- and dual-polymerized samples were significant but none was
      perceptible.

PMID- 7710626
TI  - Functional improvement of implant-retained ear epistheses with magnets and a
      retention clasp.
AB  - A method for enhanced retention and function of implant-retained ear epistheses
      is described. A cast bar containing two encapsulated magnets and a loop is
      retained on two retroauricular implants. The loop receives a clasp in the
      prosthesis and prevents its unintentional loss.

PMID- 7710627
TI  - Fracture toughness testing of visible light- and chemical-initiated provisional
      restoration resins.
AB  - This in vitro study determined the fracture toughness of four classes of resin
      using wet and dry test environments, following 48 hours of wet storage. Two of
      the resins were light initiated, while the other two were chemically initiated.
      No significant difference in fracture toughness was detected for the wet and dry
      test environments using miniature compact tension specimens. The light-initiated,
      urethane dimethacrylate resin demonstrated a significantly higher fracture
      toughness than the poly(methyl methacrylate) resin.

PMID- 7710629
TI  - Business, the profession, and ethics.

PMID- 7710628
TI  - Bond strength variation of synthetic resin teeth in dentures.
AB  - The bond strength of denture teeth to acrylic resin denture bases was determined
      by producing tensile test specimens from standardised and anonymously presented
      partial dentures. Ten dentures were produced by randomly selected commercial
      dental laboratories and five were produced in a university dental laboratory. The
      tooth debonding forces exhibited a wide range of variation both within and
      between dentures. The university-produced dentures showed, on average, a slightly
      improved tooth bond strength. This study highlights the need for further
      investigation of this problem and for the development of a standardised technique
      to provide satisfactory denture tooth bonding.

PMID- 7710630
TI  - Finite element and Weibull analysis to estimate failure risk in resin-bonded
      retainers.
AB  - Three-dimensional finite element analysis and Weibull analysis were used to
      evaluate the effect of the thickness and the rigidity of the retainers on the
      risk of failure of an anterior resin-bonded prosthesis. Retainer thickness ranged
      from 0.4 to 1.4 mm. The physical properties of metals similar to Ni-Cr and type
      IV gold alloys were used. A concentrated load (100 N) was applied to the incisal
      edge of the finite element analysis modeled pontic, and the data of other loads
      (150 to 500 N in 50-N increments) were calculated from the data of 100 N.
      Subsequent Weibull analysis revealed that failure probability diminished when
      there was an increase in metal thickness at loads of 300 to 350 N, particularly
      for the retainer made of a type IV gold alloy. The reduction in failure
      probability caused by increasing the thickness of the metal was greater when type
      IV gold alloy was used than when Ni-Cr alloy was used. This investigation
      suggests that the longevity of resin-bonded retainers can be prolonged by
      thickening the retainers, rather than using more rigid metals.

PMID- 7710631
TI  - Translucency parameter of colorants for maxillofacial prostheses.
AB  - The masking power of various generic, dry mineral earth, and flocking colorants
      dispersed in medical-grade silicone elastomer was investigated. Reflectance
      measurements were made by diffuse reflectance spectrophotometry using black and
      white backings. These data were reduced to optical scattering and absorption
      coefficients through the use of the Kubelka-Munk reflectance theory. The color
      difference between a 0.13-cm-thick layer of the colored elastomer placed on an
      ideal black backing and this layer on an ideal white backing was calculated and
      established as a translucency parameter. Using analysis of variance and stepwise
      comparison testing, significant differences were found among the translucency
      parameters of the colorants. Since these colorants differ substantially in their
      ability to mask underlying colors and since the translucency of maxillofacial
      material is an important aspect of color measurement and natural appearance,
      differences in these colorants go beyond their obvious differences in color.

PMID- 7710632
TI  - Correlation between cytotoxicity and the elements released by dental casting
      alloys.
AB  - Elements that caused cytotoxicity of high-noble, noble, and silver-based dental
      casting alloys were identified by correlating the release of elements with the
      cytotoxicities of the alloys. Release of elements was determined by atomic
      absorption spectroscopy, and the cytotoxic effect was determined by cellular
      mitochondrial function. The high-noble alloy released low levels of elements that
      did not increase after 6 hours, whereas the other alloys released higher levels
      of elements that increased over time. The cytotoxic effects of the alloys were
      attributed primarily to the release of silver and copper. In some observations,
      interactions between silver and copper were suspected of having an effect on the
      cytotoxicity.

PMID- 7710633
TI  - Cinchonine per os: efficient circumvention of P-glycoprotein-mediated multidrug
      resistance.
AB  - We have previously suggested that quinine and cinchonine could be good candidates
      for the clinical circumvention of multidrug resistance (MDR) in haematological
      malignancies because of their tolerance and their retained efficacy in serum. We
      have also shown that cinchonine was more efficient than quinine as an anti-MDR
      agent in vitro, ex vivo and in vivo after parenteral administration. Here, we
      report that cinchonine administered per os (po) is much more active than quinine
      po in circumventing MDR in rats bearing resistant colon tumours. The
      pharmacokinetics of cinchonine and quinine administered po in rat are shown to be
      very different. Cinchonine demonstrates a greater absolute bioavailability than
      quinine (44% versus 30%, respectively). Its serum concentration correlates with
      the anti-MDR activity measured ex vivo and in vivo. Cinchonine administered po
      does not significantly modify the pharmacokinetics of intravenous doxorubicin
      (DXR). However, cinchonine induces a significant increase of DXR uptake in organs
      which express the mdr1 gene (liver, kidney, lung). When associated with VAD
      (vincristine, adriamycin, dexamethasone) combined therapy in rats, cinchonine
      does not significantly increase the toxicity of the cytotoxic drugs. Based on
      these experimental data, a phase I clinical trial is currently in progress to
      test the tolerance of this potent MDR-reversing agent administered po.

PMID- 7710634
TI  - Tyrosinase-mediated cytotoxicity of 4-substituted phenols: quantitative structure
      thiol-reactivity relationships of the derived o-quinones.
AB  - Rate constants have been determined for reactions between biologically
      significant thiols, represented by cysteine and glutathione, and a series of 10 4
      substituted o-quinones, and unsubstituted o-quinone itself, generated by rapid
      disproportionation of the semiquinones formed from the corresponding catechols by
      pulse radiolysis. The quantitative structure-reactivity relationships were
      investigated by examining the correlation between the rate constants and various
      Hammett and other parameters characterizing the electronic nature of the
      substituents. From these relationships, it can be concluded that the o-quinone
      reactivity with thiols increases with the electron-withdrawing capacity of the
      substituent groups and that this effect is principally due to resonance effects.
      Such relationships allow the prediction of likely reactivities with cellular
      thiols of further o-quinones whose 4-substituents have known electronic
      parameters. These reactivities are likely to be one of the critical factors
      determining overall cytotoxicity, assisting in the choice of improved
      melanogenesis-targeted anti-melanoma drugs.

PMID- 7710635
TI  - Design of composite drug molecules: mutual effects on binding to DNA of an
      intercalator, amsacrine, and a minor groove binder, netropsin.
AB  - A variety of spectroscopic and biochemical techniques have been employed to
      investigate the extent to which binding to DNA of an intercalator (amsacrine or
      its 4-carboxamide derivative SN16713) affects the binding of netropsin, a minor
      groove-targeted ligand, and vice versa. In general, rather little mutual
      interference has been found and the binding of one drug is compatible with
      binding of the other. The anilinoacridines exert little or no effect on the
      positioning of netropsin in the minor groove, judged by circular dichroism
      spectroscopy and electric linear dichroism, whereas netropsin has a perceptible
      effect on the intercalative binding of amsacrine, but not that of SN16713.
      Neither acridine drug prevents the netropsin-induced Z-->B structure reversion
      observed with poly(dG-dC).poly(dG-dC) in buffer containing 60% ethanol. The
      kinetics of dissociation of any one drug from its DNA complex are affected
      little, if at all, by the simultaneous presence of the other. Footprinting
      experiments with the several drugs singly or in combination reveal a certain
      amount of mutual interference, but the selective recognition of AT-rich sequences
      by netropsin tends to dominate the recognition pattern and is largely maintained
      in the presence of a considerable excess of amsacrine or its 4-carboxamide
      derivative.

PMID- 7710636
TI  - Influence of the methyl substituents of a thiazole-containing lexitropsin on the
      mode of binding to DNA.
AB  - We have studied the DNA-binding properties of two thiazole-containing analogues
      of netropsin which differ by the absence (Thia-Nt) or presence (Methia-Nt) of
      methyl groups on the thiazole rings. The mode of binding to DNA of the two
      lexitropsins was investigated by circular dichroism, electric linear dichroism
      and viscosity measurements. The spectroscopic and hydrodynamic results indicate
      that the non-methylated lexitropsin binds to the minor groove of DNA, whereas the
      methylated analogue behaves as an intercalator. Our findings led to the notion
      that the methyl substituents on the thiazole rings might play a significant part
      in the intercalation process.

PMID- 7710637
TI  - Structure-cytotoxicity relationship of tilivalline derivatives.
AB  - Tilivalline (TV) possesses a pyrrolo[1,4]benzodiazepine nucleus and an indole
      substituent in its structure, and is cytotoxic toward mouse leukemia L1210 cells.
      In order to obtain more effective compounds, we have previously synthesized a
      variety of TV analogues. In this study, the cytotoxicity of these compounds has
      been evaluated. Among the compounds tested, the 11-beta-cyano compound, a TV
      analogue bearing the cyano group instead of the indole group, is approximately
      100 times more cytotoxic than TV itself. The alpha-epimer of this cyano compound
      has about one-hundredth the cytotoxicity of the 11-beta-cyano compound. Structure
      cytotoxicity relationships are discussed, including the effects of stereoisomers
      (alpha and beta) at the 11 position and substitution at the benzene moiety of TV.

PMID- 7710638
TI  - Potential suitability of Na+/K(+)-transporting ATPase in pre-screens for anti
      cancer agents.
AB  - Twenty-five compounds [digitalis (generic name for cardenolides, bufadienolides
      and their glycosides) representatives and derivatives, various steroids as well
      as some customary carcinostatics] have been compared in terms of their potency to
      suppress the proliferation of Ehrlich mouse ascites carcinoma (EMAC) cells and to
      inhibit the activity of Na/K-ATPase from EMAC cells and from human cardiac
      muscle. The inhibitor susceptibilities of the Na/K-ATPase isoforms of EMAC and
      cardiac muscle are very different, in favour of the cardiac muscle with the
      digitalis-like acting steroids, whereas they are quite similar with the digitalis
      unlike acting compounds. Whereas the K0.5 values for the inhibition of EMAC Na/K
      ATPase display the expected dependence on steroid structure, the IC50 values for
      the suppression of EMAC cell proliferation all lie within a narrow concentration
      range. With ouabain, the IC50 value for the suppression of proliferation of
      oestrogen receptor-negative, human mammary carcinoma (MCA) cells is four orders
      of magnitude higher than the K0.5 value for inhibition of the activity of human
      cardiac muscle Na/K-ATPase. In contrast to this effectivity order, some synthetic
      derivatives of digitalis steroids develop primarily antiproliferative potency.

PMID- 7710639
TI  - The Charles Bonnet syndrome: a type of organic visual hallucinosis.
AB  - The Charles Bonnet syndrome consists of visual hallucinations usually described
      in patients with bilateral eye pathology. The hallucinations are vivid and
      usually of a pleasant nature. Patients ordinarily maintain insight into the
      unreal nature of the visions. The syndrome appears to have an ophthalmologic and
      neurologic disease etiology. Treatment involves correction of the decreased
      visual acuity.

PMID- 7710640
TI  - Clozapine use in female geriatric patients with psychoses.
AB  - This study was undertaken to evaluate the clinical response of geriatric patients
      with psychoses to the atypical neuroleptic drug, clozapine. Records of patients
      over 60 years of age (n = 12, all female) who had received clozapine over a 30
      month period from selected hospitals in Western Pennsylvania were reviewed. Among
      the six patients who were rapidly titrated (300 mg/day in 3 weeks), none are
      currently receiving clozapine, while four patients who received a slower
      titration and lower dosage (range, 25 mg/day to 300 mg/day; mean, 150 mg/day)
      remain clinically improved on stable doses of clozapine. Postural hypotension
      affected seven patients, and was the reason for discontinuation of clozapine in
      five patients. One patient experienced nonfatal agranulocytosis, and one subject
      experienced leukopenia. One patient died from causes unrelated to clozapine. This
      retrospective study suggests both a low-dose and slow-titration strategy for
      initiating clozapine among elderly patients, similar to the use of other
      psychotropic drugs in the elderly, as well as close attention to postural
      hypotension, agranulocytosis, and drug interactions.

PMID- 7710641
TI  - Trait shyness in the elderly: evidence for an association with Parkinson's
      disease in family members and biochemical correlates.
AB  - The emergence of potential treatments to slow the progression of idiopathic
      Parkinson's disease (PD) has increased the need for early identification of
      persons at risk. Although considered controversial, some prior studies indicate
      that PD patients may have premorbid histories of greater trait introversion or
      shyness as well as increased rates of disorders associated with shyness (e.g.,
      anxiety, affective disorders, and irritable bowel syndrome). Essential features
      of trait shyness include (a) inhibited and avoidant behaviors and (b)
      physiological hyperreactivity to the novel or unfamiliar. In parallel, (a)
      depression in PD patients is associated with increased harm avoidance (a possible
      serotonergic function), and (b) PD patients have premorbid and comorbid decreases
      in novelty-seeking (a possible dopaminergic function). Taken together, previous
      research suggests the following hypotheses: (1) given evidence for marked
      heritability of shyness, shy elderly should report higher rates of PD in their
      family members than would nonshy elderly; and (2) shy elderly without PD should
      exhibit psychological and biologic characteristics similar to those reported in
      PD. Two groups, representing the top 27% (n = 37) and bottom 31% (n = 43) of
      scores on a standardized shyness scale, were drawn from a larger cohort of 138
      older adults (ages 50-90) living in an active retirement community. Seventeen
      percent of the shy versus 2% of the nonshy reported PD in a family member or self
      (P < .05). Shy elderly were significantly more anxious (P < .01) and depressed (P
      < .05) than were the nonshy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7710642
TI  - Depression, insight, and personality changes in Alzheimer's disease and vascular
      dementia.
AB  - Although it is generally believed that depression, retained insight, and
      preserved personality occur more frequently in vascular dementia than in
      Alzheimer's disease, there is little empiric evidence for this presumption. Most
      studies on this subject have been carried out with severely demented inpatients,
      and confounding factors such as age, sex, and severity of dementia have not been
      sufficiently taken into account. We compared 48 patients with relatively mild
      vascular dementia with 48 patients with Alzheimer's disease, matched for age,
      sex, and stage of dementia, to investigate if depression, lack of insight, and
      personality changes were related to the cause of dementia. The two groups did not
      differ regarding the incidence of major depression, the mean depression score,
      the awareness score, or the sum of scores on the items of the Blessed Dementia
      Scale concerning personality changes. We conclude that depression, lack of
      insight, and personality changes do not favor an etiology of vascular dementia
      over that of Alzheimer's disease. The present findings underscore the notion that
      the severity of the dementia should be considered in studies on the differences
      between vascular dementia and Alzheimer's disease.

PMID- 7710643
TI  - Neuroleptic malignant syndrome in the elderly.
AB  - Four cases of neuroleptic malignant syndrome (NMS) were identified in a general
      hospital over a 5-year period. Two cases presented to the psychiatric
      consultation liaison service, and two were found by a computerized review of
      discharge diagnoses. Cases were examined for age, sex, administered neuroleptic
      potency and dose, premorbid history, prodromal symptoms, methods of treatment,
      and clinical outcome. The mean age of cases was found to be 14 years greater than
      the age of the non-NMS patient population. All NMS cases had premorbid
      neuropsychiatric disorders and recognizable prodromal symptoms. The mean
      neuroleptic dose was significantly lower than in previously reported cases. A
      systems model integrating premorbid factors, intercurrent illness, and drug
      effects in pathogenesis is presented.

PMID- 7710644
TI  - Role of the dorsomedial nucleus of the thalamus in Alzheimer's disease.
AB  - It is not known whether changes in the thalamus play a role in the memory loss or
      dementia of Alzheimer's disease (AD), although trauma, infarction, and hemorrhage
      to the thalamus, particularly the dorsomedial nucleus (DMN), can cause these
      cognitive changes. To determine the pathologic changes in the DMN in AD, we
      examined the DMN in 16 cases of AD and 7 age-matched controls, with quantitative
      assessments of the total neuronal population and synaptic density, Alz-50
      positive neurons, neurofibrillary tangles (NFT), and senile plaques (SP). We
      examined sections after staining with cresyl violet, a silver stain, and
      immunocytochemical staining for Alz-50 and synapsin I. Stereologic analysis
      demonstrated a mean loss of 29% of DMN neurons in AD and a synaptic density
      decrease of 21%. Alz-50 staining and NFT were present in all AD cases but in none
      of the controls. Senile plaques were 52 times more frequent in the DMN in AD than
      in the age-matched controls. The large variation in pathologic changes among our
      AD cases suggests that neuronal losses and other pathology in the DMN in AD may
      contribute to the total brain burden of pathology resulting in dementia in some
      AD patients, but not in others.

PMID- 7710645
TI  - Influence of demographic variables on the Dementia Rating Scale.
AB  - Demographic characteristics influence many cognitive assessment tools. We
      evaluated the impact of age, education, and gender on the Dementia Rating Scale
      (DRS) in a sample of 212 normal people. Separate regression analyses revealed
      that age was the most potent demographic factor, whereas education and gender had
      little impact. However, the amount of variance accounted for by age was small
      (less than 20%). Clinical utility of age-adjusted DRS total score cut-offs was
      investigated in samples of Alzheimer's and Parkinson's disease patients. Hit rate
      analysis revealed greater sensitivity for a single cut-off value than age
      corrected cut-off scores. Overall, these findings revealed the lack of a
      clinically meaningful relationship between demographic characteristics and DRS
      scores, suggesting that age, education, and gender can be ignored for
      interpretative purposes based on cut-off scores.

PMID- 7710646
TI  - Effect of depression on dementia presentation: qualitative assessment with the
      Qualitative Evaluation of Dementia (QED).
AB  - Two novel, bedside, dementia assessment instruments, the Executive Interview
      (EXIT) and the Qualitative Evaluation of Dementia (QED) were used to examine the
      effects of DSM-III-R major depressive episodes on the clinical presentation of
      patients diagnosed with NINCDS "possible" AD. Intergroup comparisons were made of
      the various bedside cognitive measures given to 102 of 118 consecutive patients
      presenting to a university geriatric assessment clinic and consultation service.
      The assessment instruments used were: (1) the EXIT: a 15-minute, 25-item bedside
      interview for the assessment of executive control function (ECF); (2) the QED: a
      brief, clinically based checklist that operationalizes the approach of a
      geriatric psychiatrist to the qualitative assessment of dementing illnesses (when
      QED scores are mapped against EXIT scores, a qualitative picture of dementia
      typology emerges); and (3) the Mini-Mental State Exam (MMSE): a familiar bedside
      measure of cognitive function. Depressed and nondepressed patients differed
      significantly on the QED. There was no overlap in the QED scores of patients with
      probable AD versus those with depression. The QED discriminated between depressed
      and nondepressed patients with possible AD. Possible AD patients with depression
      could not be qualitatively distinguished from those with depression alone,
      although they could be discriminated by the EXIT. Only 44% of possible AD cases
      fall within the EXIT x QED 90% confidence limits for probable AD. No differences
      were found on either the QED or the MMSE between depressed non-AD patients and
      nondepressed patients exhibiting "dementia with no cortical features." The MMSE
      was insensitive to cognitive impairment in non-AD cases. NINCDS "possible" AD is
      a qualitatively heterogeneous group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7710647
TI  - Dementia of the frontal type: neuropsychological and [99Tc]-HM-PAO SPET features.
AB  - Dementia of the frontal type (DFT) is a degenerative disorder with early
      behavioral and language disturbances and with relative preservation of memory and
      visuospatial abilities. On neuropathology, DFT lacks the pathologic hallmarks of
      Alzheimer's disease (AD). We assessed the neuropsychological and SPET imaging
      features of 11 DFT and 16 AD patients. The two groups had similar performances on
      verbal learning, while the former had significantly higher nonverbal learning
      scores. Testing of verbal and nonverbal instrumental abilities showed that this
      different behavior could be due to poorer verbal fluency of DFT patients, and not
      necessarily to poorer learning. Neuropsychological data indicated that the often
      reported sparing of memory in daily functions of DFT patients can also be shown
      with formal neuropsychological testing of nonverbal learning. SPET showed a
      comparatively higher perfusion deficit of frontal regions in the left hemisphere
      of DFT patients, suggesting that this region might be affected more often in the
      disease.

PMID- 7710648
TI  - Delusional jealousy in Chinese elderly psychiatric patients.
AB  - Studies on the delusion of jealousy are scanty, especially in the elderly
      population. This study is a retrospective case note study investigating the
      prevalence of delusions of jealousy in an elderly psychiatric population in Hong
      Kong. A total of 349 patients were surveyed and five had delusions of jealousy.
      This gives an overall prevalence of 1.4%, which shows that delusions of jealousy
      in the elderly are more common than one would expect. There is a predominance
      among female patients, and the most common psychiatric diagnosis of these
      patients is delusional disorder.

PMID- 7710649
TI  - Assessment of disruptive behavior/agitation in the elderly: function, methods,
      and difficulties.
AB  - Disruptive behaviors and agitation affect caregivers, causing depression, burden,
      and stress that affects caregivers' social life, morale, and somatic health.
      Agitated behaviors may also signal that the patient is distressed, and because of
      a combination of agitated behaviors and loss of communication skills, the
      demented elderly person may not receive adequate assessment or treatment. This
      paper describes the different methods used to assess behavioral problems, their
      advantages and limitations, as well as their impact on clinical work and on
      research. Future directions in the areas of research needs, assessment
      development, and methodologic implications are also discussed.

PMID- 7710650
TI  - Relationship between affective disorders and Axis II diagnoses in geropsychiatric
      patients.
AB  - Twenty-four geropsychiatric outpatients and 52 inpatients diagnosed with
      affective disorders (ADs) via psychiatric evaluation were administered the
      Structured Interview for Disorders of Personality-Revised (SIDP-R). A chart
      review yielded 1-year relapse rates for the inpatient sample. Data indicate a 63%
      personality disorder prevalence rate for the total sample, and a 21% relapse rate
      for inpatients. No significant differences were found in PD rates between elderly
      depressed and bipolar patients, and there were no differences in relapse rates
      for those with and without PDs. Results were discussed in relation to the sizable
      frequency of PDs in this elderly sample of ADs, the possible effects of severe
      depression on the personality ratings of older adults, and the differential
      prognostic value of PDs for geropsychiatric inpatients versus outpatients.

PMID- 7710651
TI  - A pilot study of dementia in Ibadan, Nigeria.
AB  - The initiation of collaborative research involving investigators in developing
      and developed nations is a complex task. Four key areas to consider in
      collaborative, international research studies are discussed: administrative
      concerns, resources, understanding the research design, and problem solving. An
      example of a successful, international collaborative study of dementia in Ibadan,
      Nigeria is presented. Factors contributing to the successful outcome are
      detailed. The importance of the four key areas in the effective implementation of
      a research project are illustrated.

PMID- 7710652
TI  - Quantitative assessment of movement in Alzheimer's disease.
AB  - To determine whether bradykinesia in patients with Alzheimer's disease is
      different from the slowing of movement seen in normal aging, 25 patients with
      mild to moderately severe Alzheimer's disease and 25 normal controls, matched for
      age and sex, were studied. The measures of motor performance included two
      computerized tests of finger tapping, one test of point-to-point arm movements,
      and one test of gait cadence. Patients performed significantly more slowly than
      controls on all three types of motor speed measurements, with average decrements
      of 9% to 19%. Right index finger tapping, right arm point-to-point, and left arm
      point-to-point tests produced the most significant discrimination of patients
      from controls. One month test-retest reliability in patients was high for these
      measures. Bradykinesia measured by these tests was correlated with cognitive
      tests requiring concentration and executive functions, suggesting a relationship
      to frontal lobe disease. Bradykinesia in Alzheimer's disease differs
      quantitatively from the effects of normal aging on movement. Motor function can
      be reliably measured in Alzheimer's disease patients by simple and rapid tests of
      tapping speed, which may be useful as functional parameters in studying disease
      progression and response to pharmacologic intervention.

PMID- 7710653
TI  - Asthma and airway inflammation: potential anti-inflammatory activities of
      phosphodiesterase inhibitors.
AB  - Asthma is now recognized as an inflammatory disease associated with eosinophil
      infiltration into the pulmonary tissue. It has appeared in recent years that
      phosphodiesterase type IV inhibitors presented all the necessary characteristics
      to be used as new anti-asthmatic drugs. Indeed, in addition to their
      bronchodilator properties, they have inhibitory activities on inflammatory cell
      infiltration into the lung and on inflammatory mediator release. However, the
      mechanism of action of phosphodiesterase inhibitors, theoretically linked to the
      increase in intracellular cAMP, is now largely open for discussion.

PMID- 7710654
TI  - [Severe acute asthma].
AB  - Serious acute asthma is a reality. The authors detail the factors that cover the
      areas usually met, the signs that are portents of a worrying development,
      regrouped to the threshold of the entirety of the "menacing syndrome", finally
      the signs of severity or distress, as well as the recommended treatments.

PMID- 7710655
TI  - [Therapeutic management of asthma].
AB  - The clinical manifestations of bronchial asthma fall into two categories: acute
      asthma which consists of asthmatic attacks and their variants, and chronic
      asthma. The treatment of acute asthma is now well established, while that of
      chronic asthma, more difficult to organize, is part of a true therapeutic
      strategy which has two aspects: A more global approach to the treatment must be
      developed. This means full management of asthmatic patients who must be
      instructed and considered as active partners in the prevention of acute attacks,
      the evaluation of the severity of their disease and the application of the
      treatment prescribed. An asthma severity scale must be devised and a specific
      therapeutic programme must be offered for each stage of the disease. The general
      principle, beside treatment of acute asthma, is to pay much attention to the
      intercritical situation and, in particular, to treat effectively the bronchial
      inflammation.

PMID- 7710656
TI  - [Occupational asthma: retrospective study of a series of 144 cases].
AB  - The occupational origin of asthma is only found only late, from a diagnosis delay
      due to development. The aim of this work was to study the chronological
      characteristics of occupational asthma of different etiologies and to understand
      the occupational after-effects. A series of 144 cases were analysed (115 men and
      29 women) who were seen in a consultation that specialised in occupational
      pathology, with the inclusion criteria those of the National Institute for
      Occupational Safety and Health (NIOSH). The analysis was based on: the causative
      allergen or work protocol; the role of atopy; length of the latency phase; length
      of symptom exposure; diagnosis delay; occupational consequences. Asthma from
      isocyanates and flour between them accounted for 62% in this series. These were
      followed by asthma from wood (8.3%) and persulphates (7.6%). The mean length of
      the latency period was 7.5 years and the mean diagnosis delay was 2.5 years.
      Clinical history of atopy and the existence of rhinitis were much more common for
      the "biological" than the "chemical" asthmas (respectively 69% and 95%, against
      36% and 15%). Amongst the 64% of patients who benefited from complete removal of
      the allergen, 78.5% who were cured or improved, though for those who kept the
      same conditions of work there was a persistence or even aggravation of symptoms.
      In 74 cases a certificate of occupational illness was given to the patient.

PMID- 7710657
TI  - Homology between the seed cytolysin enterolobin and bacterial aerolysins.
AB  - Enterolobin, a 55-kDa cytolytic, inflammatory, and insecticidal protein isolated
      from seeds of the Brazilian tree Enterolobium contortisiliquum (Leguminosae
      Mimosoideae) has been further purified and partially sequenced by using both
      manual and automated methods. A computational search of enterolobin partial amino
      acid sequence against the PIR database revealed possible sequence similarities
      with aerolysins, cytolytic proteins from Aeromonas species. An alignment of
      enterolobin partial sequence to the amino acid sequences of A. hydrophila and A.
      sobria aerolysins showed several similar regions with many residue identities.
      The seed protein enterolobin and the bacterial aerolysins may be homologous
      proteins despite the distant phylogenetic relationship.

PMID- 7710658
TI  - Primary structure of hemoglobin from cobra Naja naja naja.
AB  - Cobra snake Naja naja naja hemoglobin shows four bands on Triton electrophoresis.
      We present the primary structure of one alpha and one beta chain. The separation
      of polypeptide chains was achieved by ion exchange chromatography on
      carboxymethyl cellulose column. The amino acid sequence was established by
      automatic Edman degradation of the native chains and tryptic and hydrolytic
      peptides in a gas-phase sequencer. The structural data are compared with those of
      human and other reptile hemoglobins and reveal not only large variations from
      human but within reptiles. The amino acid exchanges involve several subunit
      contacts and heme binding sites. This is the first study on the hemoglobin of a
      land snake. There are only two amino acid sequences of sea snake hemoglobin
      (Microcephalophis gracilis gracilis and Liophis miliaris) reported in the
      literature.

PMID- 7710659
TI  - An energy-minimized casein submicelle working model.
AB  - To develop a molecular basis for structure-function relationships of the complex
      milk protein system, an energy-minimized, three-dimensional model of a casein
      submicelle was constructed consisting of kappa-casein, four alpha s1-casein, and
      four beta-casein molecules. The models for the individual caseins were from
      previously reported energy-minimized, three-dimensional structures. Docking of
      one kappa-casein and four alpha s1-casein molecules produced a framework
      structure through the interaction of two hydrophobic antiparallel sheets of kappa
      casein with two small hydrophobic antiparallel sheets (residue 163-174) of two
      preformed alpha s1-casein dimers. The resulting structure is approximately
      spherically symmetric, with a loose packing density; its external portion is
      composed of the hydrophilic domains of the four alpha s1-caseins, while the
      central portion contains two hydrophbic cavities on either side of the kappa
      casein central structure. Symmetric and asymmetric preformed dimers of beta
      casein formed from the interactions of C-terminal beta-spiral regions as a hinge
      point could easily be docked into each of the two central cavities of the alpha
      kappa framework. This yielded two plausible energy-minimized, three-dimensional
      structures for submicellar casein, one with two symmetric beta-casein dimers and
      one with two asymmetric dimers. These refined submicellar structures are in good
      agreement with biochemical, chemical, and solution structural information
      available for submicellar casein.

PMID- 7710660
TI  - Comparison of the three-dimensional molecular models of bovine submicellar
      caseins with small-angle X-ray scattering. Influence of protein hydration.
AB  - To test the applicability of two energy-minimized, three-dimensional structures
      of the bovine casein submicelle, theoretical small-angle X-ray scattering curves
      in the presence and absence of water were compared to experimental data. The
      published method simulates molecular dynamics of proteins in solution by
      employing adjustable Debye-Waller temperature factors (B factors) for the
      protein, for the solvent, and for protein-bound water. The programs were first
      tested upon bovine pancreatic trypsin inhibitor beginning with its known X-ray
      crystal structure. To approximate the degree of protein hydration previously
      determined by NMR relaxation experiments (0.01 g water/g protein), 120 water
      molecules were docked into the large void of the kappa-casein portion of the
      structure for both the symmetric and asymmetric casein submicelle models. To
      approximate hydrodynamic hydration (0.244 g water/g protein), 2703 water
      molecules were added to each of the above structures using the "droplet"
      algorithm in the Sybyl molecular modeling package. All structures were then
      energy-minimized and their solvation energies calculated. Theoretical small-angle
      X-ray scattering curves were calculated for all unhydrated and hydrated
      structures and compared with experimentally determined scattering profiles for
      submicellar casein. Best results were achieved with the 120-bound-water structure
      for both the symmetric and asymmetric submicelle models. Comparison of results
      for the protein submicelle models with those for the theoretical and literature
      values of bovine pancreatic trypsin inhibitor demonstrates the applicability of
      the methodology.

PMID- 7710662
TI  - Initiation of visual-guided random saccades and remembered saccades in
      parkinsonian patients with severe motor-fluctuations.
AB  - We studied the initiation of saccades to visual-guided random time and remembered
      targets in a group of nine Parkinsonian patients with severe motor fluctuations
      and in 9 age matched control subjects. In contrast to a marked skeletomotor
      improvement during the "on" condition, saccadic latencies for both visual-guided
      random saccades and remembered saccades were increased in the patients during the
      "on" condition compared to the "off" condition. This result of dissociation
      between skeletomotor and oculomotor function indicates that common concepts of
      saccadic initiation in parkinsonian patients do not hold true in patients with
      severe fluctuations since dopaminergic stimulation seems to increase saccadic
      latencies in these patients.

PMID- 7710661
TI  - Analysis of exposed regions on the main extracellular domain of mouse
      acetylcholine receptor alpha subunit in live muscle cells by binding profiles of
      antipeptide antibodies.
AB  - To study the structural organization of the main extracellular domain of the
      nicotinic acetylcholine receptor (AChR) alpha subunit in live muscle cells, we
      examined the native membrane-bound receptors in cultured mouse skeletal muscle
      cells for their ability to bind a panel of antibodies against uniform-sized
      overlapping synthetic peptides which collectively represent this entire domain.
      The binding profile indicated that the regions alpha 23-49, alpha 78-126, alpha
      146-174, and alpha 182-210 are accessible to binding with antibody. Residues
      alpha 23-49, alpha 78-126, and alpha 194-210 contain binding regions for alpha
      neurotoxin and some myasthenia gravis autoantibodies. A comparison of this
      binding profile with the profile obtained for membrane-bound Torpedo californica
      AChR in isolated membrane fractions showed some similarities as well as
      significant differences between the subunit organization in the isolated membrane
      fraction and that in the membrane of live muscle cells. Regions alpha 89-104 and
      alpha 158-174, which are exposed in the isolated membrane fraction, are also
      exposed in the live cell. On the other hand, regions alpha 23-49, and alpha 182
      210, which are exposed in the live cell, are not accessible in the isolated
      membrane and, furthermore, the region alpha 1-16, which has marginal
      accessibility in the cell, becomes highly accessible in the membrane isolates.
      The exposed regions defined by this study may be the primary targets for the
      initial autoimmune attack on the receptors in experimental autoimmune myasthenia
      gravis.

PMID- 7710663
TI  - Cerebrospinal fluid ferritin levels of patients with Parkinson's disease,
      Alzheimer's disease, and multiple system atrophy.
AB  - Iron is believed to play a role in the pathogenesis of both Parkinson's disease
      (PD) and Alzheimer's disease (AD). We measured ferritin, which is considered to
      be the iron storage protein, in CSF of patients with PD, AD, and multiple system
      atrophy (MSA) as well as control subjects. We found a significant increase in CSF
      ferritin in AD compared with both PD and age-matched controls. No significant
      differences were found between PD patients with dementia (PDD) and non-demented
      PD patients. For non-demented PD patients a positive correlation between CSF
      ferritin and age was found. Our results may indicate that iron has a role in the
      pathophysiology of AD.

PMID- 7710664
TI  - MPTP-induced behavioural and biochemical deficits: a parametric analysis.
AB  - Two experiments were performed to study the parametric effects of long-term
      administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP), as a functional model of parkinsonism in mice. The behavioural deficits
      induced by different doses of MPTP (5, 10, 20, 30 or 40 mg/kg, s.c., each
      injected on two occasions) at a 3-week or a 3-month treatment-testing interval
      were evidenced by significant reductions of spontaneous motor activity, from the
      10 mg/kg dosages upwards at the 3-week interval and from 30-40 mg/kg at the 3
      month interval. Significant dopamine (DA) reductions in the mouse striatum were
      obtained at these dose levels and intervals. The behavioural deficit of the 40
      mg/kg dose (injected on two occasions) and tested at the 3-, 6-, 12-, 24- and 40
      week intervals (separate as well as repeated testing groups) indicated marked and
      relatively comparable reductions of all three parameters of motor activity,
      locomotion, rearing and total activity. DA depletions were severe at all five
      test intervals. These results offer functional and neurochemical evidence that
      MPTP treatment produces permanent damage to the nigrostriatal motor system in
      mice.

PMID- 7710665
TI  - Potentiation of dopamine-dependent locomotion by clonidine in reserpine-treated
      mice is restricted to D2 agonists.
AB  - Mice treated with reserpine (5 mg/kg IP), 24 h beforehand, were completely
      akinetic. Fluent locomotion was reinstated with the D1-selective agonist SKF
      38393 (3-30 mg/kg IP), the D2-selective agonist RU 24213 (0.5-5 mg/kg SC) and the
      mixed D1/D2 agonist apomorphine (0.025-0.5 mg/kg SC). Clonidine (0.03125-1 mg/kg
      IP) caused a dose-dependent sedation in dopamine-intact mice, but had no effect
      by itself on the locomotor activity of monoamine-depleted mice. In drug
      interaction experiments, clonidine did not modify the motor stimulant action of
      SKF 38393, but greatly enhanced the motor responses to RU 24213 and apomorphine.
      These results support the hypothesis that alpha-adrenoceptor agonists facilitate
      dopamine D2 but not dopamine D1 motor responding in the reserpine-treated mouse
      model of Parkinson's disease.

PMID- 7710666
TI  - Antiparkinsonian action of MK-801 on the reserpine-induced rigidity: a
      mechanomyographic analysis.
AB  - MK-801, a non-competitive antagonist of NMDA receptors, is known to exhibit a
      beneficial action in many animal models of Parkinson's disease. The aim of this
      study was to examine the influence of MK-801 on the reserpine-induced muscle
      rigidity. The rigidity was estimated by a direct mechanomyographic method. This
      method consists in successive bending and straightening of a rat's hind foot in
      the ankle joint and measuring the resistance of the foot to passive movements.
      Reserpine in doses of 5-10 mg/kg ip, given alone or in combination with alpha
      methyl-p-tyrosine (alpha MT, 250 mg/kg ip), induced rigidity. The strongest
      muscle rigidity was induced by 10 mg/kg of reserpine 1 hour after administration.
      MK-801 (0.32-1.28 mg/kg sc) injected 70 min after reserpine (10 mg/kg ip)
      decreased the rigidity induced by the latter compound. Similarly, MK-801 (1.28
      mg/kg sc), administered 27 h 40' after joint treatment with reserpine (10 mg/kg
      ip) and alpha MT (250 mg/kg ip), strongly inhibited the reserpine-induced muscle
      rigidity. The obtained results show that the glutamatergic hyperactivity plays a
      significant role in the reserpine-induced rigidity. As the reserpine-induced
      motor disturbances are commonly accepted to be an animal model of parkinsonian
      symptoms, it may be assumed that the NMDA receptor blocking component may
      contribute substantially to the therapeutic action of antiparkinsonian drugs.

PMID- 7710667
TI  - The roles of neuromelanin, binding of metal ions, and oxidative cytotoxicity in
      the pathogenesis of Parkinson's disease: a hypothesis.
AB  - A characteristic feature of both Parkinson's disease (idiopathic paralysis
      agitans) and normal aging is loss of pigmented neurons in the substantia nigra.
      This has been found to correlate with the accumulation of neuromelanin and with
      oxidative stress in this brain region, but a clear association between these
      factors has not been established. Based on our recent demonstration that
      neuromelanin is a true melanin, containing bound metal ions in situ, we present a
      general model for its accumulation in vivo and the hypotheses (1) that it has a
      cytoprotective function in the sequestration of redox-active metal ions under
      normal conditions but (2) that it has a cytotoxic role in the pathogenesis of
      Parkinson's disease. Thus, neuromelanin accumulates normally through the
      autooxidation of catecholamines and serves tightly to bind redox-active metal
      ions, processes which would accelerate under conditions of intracellular or
      extracellular oxidative stress. Based on the known properties of melanin,
      however, neuromelanin also has the potential for exacerbating oxidative stress,
      eg by generating H2O2 when it is intact or by releasing redox-active metal ions
      if it loses its integrity; these reactions also would modulate the reactivity of
      the neuromelanin. By overwhelming intracellular antioxidative defense mechanisms,
      such a positive-feedback cycle could turn a condition of chronic or repeated
      oxidative stress in vulnerable neurons into an acute crisis, leading to cellular
      death. If the cumulative stress in duration and/or degree is severe enough,
      neuronal depletion could be sufficient to cause Parkinson's disease during life.
      One possible trigger for this cascade is suggested by the increased nigral iron
      contents in postmortem parkinsonian brains and the correlation of this disease
      with urban living where exposure to heavy metal ions is high: the saturation of
      neuromelanin with redox-active metal ions. Parkinson's disease therefore may be a
      form of accelerated aging in the substantia nigra associated with environmental
      toxins in which neuromelanin has a central, active role.

PMID- 7710668
TI  - Are NMDA antagonistic properties relevant for antiparkinsonian-like activity in
      rats?--case of amantadine and memantine.
AB  - Amantadine (25, 50, 100 mg/kg), memantine (5, 10, 20 mg/kg) and MK-801 (0.05,
      0.1, 0.2 mg/kg), all having NMDA channel blocking properties, were compared in
      three tests used for screening of antiparkinsonian agents in rats, namely:
      haloperidol-induced catalepsy, locomotor activity in monoamine depleted rats and
      rotation in rats with a unilateral substantia nigra lesion. Additionally, plasma
      levels of amantadine and memantine were assessed to gain an insight into the
      concentration ranges achieved at behaviorally active doses. Amantadine and (+)-MK
      801 produced dose-dependent inhibition of haloperidol-induced catalepsy while
      memantine was less efficacious producing clear-cut anticataleptic action at a
      dose of 10 mg/kg only but failing at 20 mg/kg due to myorelaxant activity. All
      agents attenuated sedation in monoamine depleted rats with amantadine being the
      least and MK-801 being the most effective. The same rank order of efficacy was
      seen in inducing ipsilateral rotations in rats after a substantia nigra lesion.
      On the basis of the present study and published data, it can be assumed that the
      doses of amantadine, memantine and MK-801 showing antiparkinsonian-like activity
      in animals result in plasma levels leading to NMDA antagonism. However, in the
      haloperidol-induced catalepsy test the efficacy of amantadine was higher than
      memantine, while the opposite was true for rotation and reserpine-induced
      sedation indicating pharmacodynamic differences between both agents.

PMID- 7710669
TI  - Cerebrospinal monoamine metabolites and amino acid content in patients with
      parkinsonian syndrome and rats lesioned with MPP+.
AB  - Monoamine metabolites and amino acid concentration in cerebrospinal fluid (CSF)
      of 33 untreated patients with parkinsonian syndrome, and 20 control patients
      without specific neurological symptoms have been compared with those obtained in
      cerebrospinal fluid of rats intrastriatally lesioned with 1-methyl-4
      phenylpyridinium ion (MPP+) and sham operated animals. Homovanillic acid content
      was found to be significantly lower in patients with severe parkinsonism (motor
      score of UPDRS > 24), but not in patients with mild symptoms (motor score < or =
      24). A correlation between the loss of striatal dopamine and the decrease in
      cerebrospinal homovanillic acid has been established in rats treated with MPP+.
      The extrapolation of these results to those obtained from human patients could be
      important in assessing the degree of striatal dopamine loss shown by humans with
      parkinsonian syndrome at the moment of clinical diagnosis. No significant
      differences were found between the other monoamine metabolites analyzed and free
      amino acid content in human and rat CSF.

PMID- 7710670
TI  - Effect of nerve growth factor and GM1 ganglioside on the recovery of cholinergic
      neurons after a lesion of the nucleus basalis in aging rats.
AB  - A unilateral ibotenic acid lesion was placed in the nucleus basalis
      magnocellularis of 3- and 18-month-old rats. In the lesioned aging rats, the
      number of choline acetyltransferase-immunoreactive neurons of the nucleus basalis
      magnocellularis was markedly reduced in the ipsilateral side and to a lesser
      extent in the contralateral side. Twenty-one days after the lesion, the activity
      of choline acetyltransferase in the ipsilateral cortex was reduced by 40% in both
      groups of rats and by 24% in the contralateral frontal cortex of the aging rats.
      Intracerebroventricular administration of nerve growth factor (10 micrograms
      twice a week) to aging lesioned rats for 3 weeks after surgery resulted in a
      complete recovery in the number of choline acetyltransferase-immunoreactive
      neurons in the nucleus basalis of both sides, and choline acetyltransferase
      activity in the contralateral cortex, with little effect on the ipsilateral
      cortex. No potentiation was seen after the concurrent administration of GM1
      ganglioside and nerve growth factor. Complete recovery in cortical choline
      acetyltransferase activity was only observed in the lesioned rats treated with
      nerve growth factor for 1 week before and 3 weeks after lesioning. Nerve growth
      factor treatment, both after the lesion, and before and after the lesion,
      improved the passive avoidance performance disrupted by the lesion. In young
      lesioned rats daily intraperitoneal administration of GM1 (30 mg/kg) for 21 days
      after surgery promoted both the recovery of choline acetyltransferase activity
      and passive avoidance performance. In aging rats GM1, even at a dose twice as
      large, failed to reverse the biochemical and morphological deficits and
      behavioral impairment induced by the lesion. Only when GM1 administration was
      started 3 days before the lesion, were a complete recovery in choline
      acetyltransferase activity in the contralateral cortex and a partial recovery in
      the ipsilateral cortex obtained. Our results indicate that nerve growth factor
      and, to some extent, GM1 facilitate the recovery of the cholinergic neurons after
      a lesion of the nucleus basalis in aging rats, but their efficacy is reduced. The
      lower efficacy of GM1 as compared to NGF might be due to the different routes of
      administration used.

PMID- 7710671
TI  - Pyritinol facilitates the recovery of cortical cholinergic deficits caused by
      nucleus basalis lesions.
AB  - The effect of a nootropic, Pyritinol, on the recovery of cortical cholinergic
      deficits induced by injury of the nucleus basalis has been tested on two groups
      of unilateral quisqualic acid nbM-lesioned rats. The first group had a 30 nmol
      lesion producing a cortical cholinergic impairment at 21 days, with a spontaneous
      recovery at 45 days. The second group had a 50 nmol lesion that produced a deeper
      cholinergic deficit, which did not recover at 45 days. Pyritinol enhanced the
      recovery in the 30 nmol group of animals on the 21st day after surgery. The
      recovery was measured as an increase in the activities of acetylcholinesterase
      (AChE), choline acetyltransferase (ChAT) and the high affinity choline uptake
      system, and the histochemical densities of the cortical AChE network and the M2
      receptor. Histochemical analysis of the nbM enabled cortical recovery to be
      related to the number of surviving neurons and also to their hypertrophy and AChE
      ChAT hyperactivity. Pyritinol enhanced recovery in 30 nmol lesioned animals but
      in the other group, with a lower number of surviving neurons and a lower ability
      of the cells to become hypertrophic, the drug was unable to promote cortical
      recovery.

PMID- 7710672
TI  - Testing for mutations in exon 17 of the beta-amyloid precursor protein gene in
      Finnish Alzheimer patients and normal subjects.
AB  - Mutations in the beta-amyloid precursor protein gene on chromosome 21 were shown
      to cause a small proportion of Alzheimer's disease. We studied the occurrence of
      the point mutations in exon 17 of the beta-amyloid precursor protein gene in a
      sample of Finnish familial Alzheimer patients and nondemented controls using
      polymerase chain reaction and a single strand conformation polymorphism
      technique. In addition, mutations in familial Alzheimer's disease patients were
      studied by sequencing the amplified products. Interestingly, two probable
      polymerase chain reaction errors were detected in codons 717 and 693 of the exon
      17. However, no mutations in the exon 17 were confirmed adding the study to the
      body of literature that mutations in the exon 17 are a rare cause of familial
      Alzheimer's disease.

PMID- 7710673
TI  - Clinical significance of creatine kinase isoenzymes for fetal asphyxia in women
      at labor.
AB  - Creatine kinase-brain isoenzyme activity (CK-BB) was measured longitudinally in
      the serum of 31 pregnant women in the first stage of labor (early and advanced),
      at delivery, and 1, 6 and 24 h after delivery, in the umbilical cord and in the
      serum of their neonates on the first day of life. There was no increase in serum
      CK-BB values of mothers that delivered normally (n = 15) or had an elective
      cesarean section (n = 5). Pregnant women with signs of fetal distress had an
      increase in CK-BB levels in the first stage of labor (mean +/- SD 4.5 +/- 4.9
      U/l, p < 0.03) and 6 h after delivery (12 +/- 4 U/l, p < 0.0001). Neonates with
      intrauterine stress also had an increase in their CK-BB to 144 +/- 116 U/l at 6 h
      of life, in comparison with babies born without signs of stress. It appears that
      CK-BB during labor and in the first hours of life may be indicative of
      intrauterine stress.

PMID- 7710674
TI  - Measurement of fetal plasma levels of glutathione S-transferase B1 as an
      indicator of damage to the liver caused by hypoxia in utero.
AB  - Glutathione S-transferase B1 (GST B1) concentration in blood and amniotic fluid
      from fetuses investigated for a variety of conditions including rhesus (Rh) allo
      immunisation was assessed for its usefulness as a measure of liver damage caused
      by hypoxia in utero. The concentration in blood from the intrahepatic vein (IHV)
      was 10-fold higher than that from the placental cord insertion suggesting that
      parenchymal liver cells are damaged during blood sampling from the IHV. As a
      measure of hepatocellular impairment caused by intra-uterine hypoxia, levels were
      higher in frankly acidotic fetuses than in normally managed Rh fetuses. The
      degree of hypoxia required to trigger the release of GST B1 into the plasma
      remains unclear.

PMID- 7710675
TI  - Prediction of second trimester intrauterine growth retardation and fetal death in
      a discordant twin by first trimester measurements. Case report and review of the
      literature.
AB  - Ultrasound examination at 9 weeks of gestation in a 34-year-old primigravida
      showed a twin pregnancy, with discrepancy in the sizes of the two gestational
      sacs, whereas the crown-rump lengths and fetal heart rates were virtually
      identical-the result being an abnormal sac size/crown-rump length ratio (early
      oligohydramnios). By 14 weeks discordant heart rates and umbilical artery flow
      velocities were detected, the discordance between the twins increasing as
      pregnancy progressed. Biparietal diameters, femoral lengths, and abdominal
      circumferences were also progressively discordant, and at 28 weeks the smaller
      twin had no heart beat. At 30 weeks the patient was delivered of a live 1,350
      gram infant and a 400-gram dead fetus. This case suggests, in contradistinction
      to several previous reports, that fetal discordance in twin pregnancies (and
      perhaps intrauterine growth retardation in general) may be present as early as
      the first trimester.

PMID- 7710676
TI  - Pregnancy complicated by Ebstein's anomaly: oxygen administration to mother for
      chronic fetal hypoxemia. A therapeutic case report.
AB  - For chronic fetal hypoxia due to maternal Ebstein's anomaly, oxygen was
      administered daily to the mother by mask for 105 days. At 20 weeks of gestation,
      umbilical venous blood gases in room air showed pH 7.42, PO2 25.7 mm Hg, PCO2
      33.7 mm Hg and O2 saturation 48.7%, and changed to 7.45, 39.1 mm Hg, 25.9 mm Hg
      and 77.4% on 3 liters/min of oxygen inhalation by mask, respectively. The PO2 of
      the maternal arterial blood gases increased to 30 mm Hg on oxygen administration
      at 15 weeks of gestation, but at 25 weeks of gestation the PO2 increased by only
      about 10 mm Hg. At 30 weeks, intrauterine growth retardation was suspected. Just
      after the second puncture of the umbilical cord at 31 weeks and 3 days of
      gestation, 80 bpm fetal bradycardia occurred for several minutes without recovery
      and emergency cesarean section was done under the general anesthesia.

PMID- 7710677
TI  - Twin-to-twin transfusion syndrome: selective feticide by embolization of the
      hydropic fetus.
AB  - To improve the outcome of severe twin-to-twin transfusion syndrome with 1
      hydropic fetus and to prevent ischemic sequelae in the survivor, we developed a
      technique of selective feticide by vascular embolization of the most severely
      damaged twin. Acute second trimester polyhydramnios occurred in 4 biamniotic
      monochorial twin pregnancies, with 1 fetus normal on ultrasound but the other
      severely damaged by hydrops and hypertrophic hypokinetic cardiomyopathy. The
      hydropic fetus underwent embolization using a bolus of histoacryl injected into
      the umbilical vein and fetal heart under ultrasound guidance. In 1 triplet
      pregnancy with a set of monochorial fetuses, premature labor occurred at 26
      weeks, 2 weeks after embolization, and there were 2 neonatal deaths. The 3 other
      cases resulted in the birth of a normal infant at 31-37 weeks of gestation. This
      suggests that in twin-to-twin transfusion syndrome with severe polyhydramnios and
      hydrops of 1 fetus, embolization may salvage the other twin.

PMID- 7710678
TI  - Selective feticide in twin transfusion syndrome using ultrasound-guided insertion
      of thrombogenic coils.
AB  - Twin transfusion syndrome is a common complication of monozygotic twin
      pregnancies. Selective feticide is one of the many different aggressive and
      invasive therapies that has been suggested to improve an otherwise dismal
      perinatal outcome. The ideal method of selective feticide remains to be
      delineated for cases of twin transfusion syndrome that occur remote from term. We
      describe a case involving the use of intracardiac placement of thrombogenic coils
      to attempt selective termination.

PMID- 7710679
TI  - Fetal in situ cardiovascular and pulmonary morphology of vascular ring due to
      left aortic arch and right ductus arteriosus in rats.
AB  - We studied 17 fetal rats with vascular ring composed of the left aortic arch and
      right ductus arteriosus and 7 fetal rats with the mirror-image arrangement. The
      vascular ring of this type was induced by administration of bis-diamine (200 mg)
      on the 9th and 10th day of pregnancy in rats. In the most severe case, the
      esophagus and trachea were compressed completely and no inner space was left, and
      localized and diffuse tracheal stenosis was prominent. The fetal lung mass was
      increased as the stenosis of the ring was severe. The thoracic descending aorta
      was positioned in the left side, and was contrasted with the clinically observed
      right descending aorta in this postnatal anomaly. Thus we are reporting two new
      findings in the fetal vascular ring with the left aortic arch and the right
      ductus arteriosus: increased lung mass and left descending aorta in a fetal
      animal model.

PMID- 7710680
TI  - Associated malformations and chromosomal defects in congenital diaphragmatic
      hernia.
AB  - In order to determine the frequency of associated malformations and chromosomal
      defects in patients with congenital diaphragmatic hernia (CDH) our experiences
      with CDH during the last 8 years (1985-1993) were reviewed. During the study
      period, 33 fetuses (prenatal group) with CDH were examined at our level III
      ultrasound department. In the same period 11 neonates (postnatal group) were
      admitted to our pediatric surgical unit after postnatal diagnosis of a CDH. Those
      cases had not been suspicious for CDH during prenatal level I scan. In 24 (72.7%)
      of the cases with CDH seen prenatally, at least one or more extradiaphragmatic
      malformations could be detected. Most of them affected the cardiovascular,
      skeletal, genitourinary and nervous system. Six (18.1%) fetuses had chromosomal
      abnormalities, especially trisomy 18. In contrast to these findings just 4 of the
      11 babies (36.3%) seen postnatally had associated malformations and all of them
      had a normal chromosome set. Survival rate of fetuses with CDH and associated
      anomalies (7.1%) was poor, in contrast to those with an isolated CDH (43.7%).
      Prenatal ultrasound investigations being suspect for CDH should encourage the
      clinician to make further diagnostical efforts. This includes detailed ultrasound
      examination and cytogenetic analysis. Associated malformations as well as
      chromosomal defects are often present in affected patients.

PMID- 7710681
TI  - Ultrastructural alterations of the amniocytes in 2 patients with rubella during
      the first trimester of pregnancy.
AB  - The amniotic fluid cells of 2 patients with rubella at the 18th week of pregnancy
      were obtained during therapeutic abortion and examined with a transmission and a
      scanning electron microscope (SEM). In comparison with amniocytes of healthy
      women, those of rubella patients showed marked alterations, consisting of lack of
      heterochromatin, almost complete disappearance of the electron-dense cytoplasmic
      layer and membrane changes. The membrane damage was clearly demonstrated by SEM
      and was expressed by a decrease in the number and size of microvilli. Although
      more experience is needed for evaluation of the ultrastructure of the amniotic
      fluid cells in rubella patients, these findings may serve as an additional tool
      for the intrauterine diagnosis of rubella.

PMID- 7710682
TI  - Rapid determination of fetal sex in coelomic and amniotic fluid by fluorescence
      in situ hybridisation.
AB  - Coelomic fluid (n = 32), amniotic fluid (n = 26) and placental tissue were
      obtained from 32 women undergoing termination of pregnancy at 7-11 weeks of
      gestation. Fluorescence in situ hybridisation (FISH) was performed to determine
      fetal sex using a heterochromatic Y probe and an alpha satellite repeat probe for
      chromosome X. In each case there was concordance in the fetal sex from the three
      compartments. However, no result could be obtained from 4 of the 32 coelomic
      fluids and 4 of the 26 amniotic fluid samples. The hybridisation efficiency was
      significantly lower in coelomic and amniotic fluid compared with placental
      tissue.

PMID- 7710683
TI  - Pharmacokinetics of interferon-alpha in pregnant women and fetoplacental passage.
AB  - Interferon (IFN) therapy is currently not approved for use during pregnancy. Two
      HIV-seropositive pregnant women, who were due to undergo abortion in the second
      trimester of pregnancy, were given a single intramuscular dose of IFN-alpha, with
      their informed consent. Blood samples were taken simultaneously from the mothers
      and fetuses, together with amniotic fluid. IFN was undetectable in the fetal
      blood and amniotic fluid in both cases. Pharmacokinetic parameters were similar
      to those in nonpregnant women. We conclude that maternal IFN-alpha during
      pregnancy should be safe for the fetus. The indications for IFN therapy in
      pregnancy could therefore be the same as those in the non-pregnant state.

PMID- 7710684
TI  - Functional expression of fused enzymes between human cytochrome P4501A1 and human
      NADPH-cytochrome P450 oxidoreductase in Saccharomyces cerevisiae.
AB  - The activity of human cytochrome P450 enzymes heterologously expressed in
      Saccaromyces cerevisiae cells is limited by the yeast endogenous cytochrome P450
      oxidoreductase (yOR). To overcome these limitations, we constructed hybrids
      between human P4501A1 (CYP1A1) and human P450 oxidoreductase (hOR) by combining
      the cDNA encoding hOR with the CYP1A1 cDNA. In addition, in one construct, the
      amino terminus of hOR was replaced by the membrane anchor domain of a yeast
      protein. Anchoring of the fusion constructs in internal membranes either by the
      amino terminus of hOR or by the yeast peptide resulted in functional hybrid
      proteins, which were present in similar amounts as the authentic CYP1A1 in
      microsomal fractions of recombinant cells. Saccharomyces cerevisiae cells
      transformed with the expression plasmids produced the respective proteins in the
      expected molecular sizes reactive with both anti-CYP1A immunoglobulin (Ig) and
      anti-oxidoreductase Ig. Saccharomyces cerevisiae yOR-mutant (cpr1-) and wild-type
      (CPR1+) cells containing the fused enzymes exhibited CYP1A1-specific 7
      ethoxyresorufin-O-deethylase activities. Reduced CO-difference spectra of
      microsomal fractions containing the fused enzymes indicated a proper
      incorporation of protoheme into the CYP1A1 domains. These results show that the
      chimeric proteins represent catalytically self-sufficient monooxygenase systems.
      The hOR domains of the hybrid proteins were also functional as cytochrome c
      reductases and able to activate the yeast P450 enzyme lanosterol-14 alpha
      demethylase, indicating correct insertion of the chimeric proteins in internal
      membranes.

PMID- 7710685
TI  - Role of the liver-enriched transcription factor HNF-1 alpha in expression of the
      CYP2E1 gene.
AB  - The role of the trans-acting factor HNF-1 alpha in activating CYP2E1 gene
      expression was confirmed by transient co-transfection of an HNF-1 alpha
      expression plasmid and the CYP2E1 promoter fused to the chloramphenicol acetyl
      transferase (CAT) reporter gene. Only HNF-1 alpha, and not HNF-1 beta, HNF-4,
      C/EBP alpha, C/EBP beta, or DBP, was able to activate the CYP2E1 promoter. The
      extent of activation was proportional to the number of copies of the HNF-1
      binding sequence upstream of the promoter. Removal or mutation of the HNF-1
      binding sequence led to inactivation of the promoter in response to HNF-1 alpha.
      Gel-shift Western blot analysis using a synthetic HNF-1 binding sequence derived
      from CYP2E1 and rat liver nuclear extract revealed that the protein-DNA complex
      obtained with adult rat liver nuclear extract consisted of both HNF-1 alpha and
      HNF-1 beta proteins. The shifted bands produced by nuclear extracts from adult,
      where the endogenous CYP2E1 gene is active, and fetal rat liver, where the gene
      is inactive, were found to migrate differently, suggesting that the population of
      factors, possibly including different ratios of HNF-1 alpha and HNF-1 beta
      proteins, may change during development. However, the co-transfection study did
      not show cooperativity between the two factors. Elements upstream of the HNF-1
      binding site were found to affect the activity of the promoter negatively in the
      transfection assay. DNase I hypersensitive site mapping revealed a hypersensitive
      site in this inhibiting element in the adult rat liver sample but not in liver
      from newborn animals.

PMID- 7710686
TI  - Analysis of the Hoxd-3 gene: structure and localization of its sense and natural
      antisense transcripts.
AB  - This study set out to investigate the structure and localized expression of the
      mouse homeobox-containing gene Hoxd-3. In addition to identifying a transcript of
      the type known from other Antennapedia (Antp)-like mammalian homeobox cDNAs, an
      antisense transcript was also detected. The antisense form of Hoxd-3 overlaps
      with 603 bp of the sense transcript including the homeobox. Active antisense
      transcription has been confirmed by RNA blot analysis with single-stranded probes
      and by the direction of splicing of an intron in the antisense transcript. The
      localized expression of sense and antisense transcripts was compared by in situ
      hybridization. Hoxd-3 expression was observed from 8.5 days p.c., in the neural
      tube with a sharp border in the hind brain at the level of rhombomeres 4-5. In
      contrast, the earliest antisense expression was detected at 10.5 days p.c. in
      cDNA libraries. At 12.5 days p.c., sense and antisense transcripts colocalized in
      the liver. The possible role of antisense homeobox transcripts during liver and
      the hematopoietic development is discussed.

PMID- 7710687
TI  - Intracellular sorting of aspartylglucosaminidase: the role of N-linked
      oligosaccharides and evidence of Man-6-P-independent lysosomal targeting.
AB  - Aspartylglucosaminidase (AGA, E.C. 3.5.1.26) is a soluble lysosomal hydrolase
      that participates in the degradation of glycoproteins. Here we analyzed the
      special features in the intracellular targeting of this dimeric amidohydrolase,
      especially the role of N-linked sugars and their phosphorylation in transport and
      activity of heterodimeric aspartylglucosaminidase, using in vitro mutagenesis and
      transient expression of mutant polypeptides in COS cells. The single N
      glycosylation sites of both the alpha and beta subunits were destroyed
      individually and in combination. Just one remaining N-glycosylation site on
      either subunit was sufficient for normal processing into subunits and lysosomal
      transport, but the totally nonglycosylated enzyme, although active and processed
      into subunits, was not transported into lysosomes and became trapped in the
      endoplasmic reticulum (ER) or secreted. The intracellular targeting of AGA was
      partially disturbed by the lack of glycosylation in the beta subunit, resulting
      in accumulation of dimeric, active polypeptides in the ER, whereas lack of
      oligosaccharides in the alpha subunit did not affect the intracellular targeting
      of AGA. N-glycans in the beta subunit were found to be essential for the long
      term stability of the polypeptide in the cell, but not for initial folding or
      subunit processing into the active dimeric molecule. Both subunits have two
      glycosylation isoforms. Both forms of the alpha subunit were found to be
      phosphorylated, whereas only one of the two glycosylation isoforms of the beta
      subunit is phosphorylated. The mutant enzyme with nonglycosylated alpha subunit
      and nonphosphorylated beta subunit is transported into lysosomes, suggesting that
      AGA is capable of using an alternative, mannose-6-phosphate receptor-independent
      routing into lysosomes.

PMID- 7710688
TI  - Transient induction of the glial intermediate filament protein gene in Muller
      cells in the mouse retina.
AB  - The glial intermediate filament protein (GFAP) gene is not normally expressed by
      retinal Muller cells but it is transcriptionally activated following
      photoreceptor degeneration. In the present study, we have examined the
      relationship between progressive photoreceptor loss and changes in GFAP gene
      activity in Muller cells. In albino mice with light-induced photoreceptor
      degeneration, GFAP level was strongly elevated after 2 weeks. GFAP level remained
      high even after 3 months in light. In situ hybridization studies showed that GFAP
      transcripts were quite sparse in the first week but increased dramatically after
      2 weeks of light exposure. After 4 weeks in constant light, however, little GFAP
      mRNA was detected in Muller cells. RNA blotting also showed that there was an
      approximately 20-fold increase in GFAP mRNA content at 2 weeks; but at 4 weeks,
      the RNA content fell to about four-fold higher than the basal level. These
      results show that GFAP level remains high long after its synthesis, probably as a
      consequence of low GFAP turnover in the Muller cell cytoskeleton, while GFAP mRNA
      level rises and declines rapidly due to transient activation of the GFAP gene in
      Muller cells.

PMID- 7710689
TI  - Human dehydroepiandrosterone sulfotransferase gene: molecular cloning and
      structural characterization.
AB  - Dehydroepiandrosterone sulfotransferase (DHEA ST) catalyzes the sulfate
      conjugation of DHEA and other steroids. From 20 to 25% of subjects are included
      in a subgroup with high levels of hepatic DHEA ST activity, raising the
      possibility that this enzyme activity might be controlled by a genetic
      polymorphism. To understand the molecular mechanisms involved in regulating
      levels of DHEA ST activity in human tissue, we cloned the human DHEA ST gene,
      STD. STD spans at least 17 kb and is composed of 6 exons and 5 introns. The
      locations of the splice junctions for several of the introns are identical to
      those present in the rat phenol or aryl ST gene, the only other cytosolic ST gene
      for which the entire exon/intron structure has been reported, as well as those
      present in two partially characterized genes for the rat senescence marker
      protein, genes that are also thought to encode ST enzymes. The 5'-flanking region
      of the human STD gene does not contain canonical TATA or CCAAT elements, but this
      region is capable of promoting transcription of a reporter gene in Hep G2 cells.
      Molecular cloning and structural characterization of the human STD gene will make
      it possible to study genetic mechanisms involved in the regulation of DHEA ST
      activity in human tissue.

PMID- 7710690
TI  - Determination of gene structure by intron trapping using polymerase chain
      reaction: application to the human plasma prekallikrein gene.
AB  - We have devised a method to determine gene structure that utilizes the known gene
      structure of homologous proteins and the polymerase chain reaction (PCR). Because
      homologous proteins have evolved from a common ancestral gene, it is possible to
      design primers corresponding to the adjacent exon sequences in the protein of
      interest. These primers could then be used in a PCR using normal genomic DNA as
      template. The resultant PCR product is then subcloned and the nuceotide sequence
      of the insert is determined. This information provides the exon-intron junction
      sequences and the partial sequences of the intron. We have applied this method to
      trap introns A, H, and J of human plasma prekallikrein gene and determined their
      exon-intron junction sequences. The primers were designed based on the known cDNA
      sequence of human plasma prekallikrein and gene structures of rat plasma
      prekallikrein and human coagulation factor XI (which is 50% identical in the
      primary sequence). The intron-exon junctions are at identical sites to those of
      the rat plasma prekallikrein gene. The intron sequences thus obtained will be
      useful in designing primers for exon trapping and sequence analysis of plasma
      prekallikrein gene from patients with defective plasma prekallikrein. This
      technique will also allow the determination of the entire gene structure.

PMID- 7710691
TI  - Structure of the Drosophila melanogaster annexin X gene.
AB  - The annexin X gene was cloned in the P1 recombinant phage carrying a genomic
      sequence of approximately 70 kb long. This DNA fragment encompasses at least two
      annexin X copies and several 7.8-kb tandem units represented by an anonymous
      sequence fused to the 3' truncated part of the annexin X gene. The proteins of
      annexin family contain a variable amino-terminal domain and a core domain; the
      latter includes four structurally conserved repeats that presumably arose as a
      result of duplications. The annexin X gene of Drosophila is about 2 kb long and
      contains four exons. Exon 1 encodes four amino-terminal amino acids, exon 2
      encodes the remaining part of the amino-terminal domain and the three conserved
      repeats, and exon 3 and exon 4 encode the fourth repeat. The positions of introns
      2 and 3 are strictly conserved with respect to both the amino acid position and
      codon phase as compared to introns 10 and 12 of the fourth repeat in vertebrate
      annexin genes. We propose the existence of a primordial annexin coding structure
      comprising at least two introns whose duplications during evolution have been
      followed by the loss of ancient introns in the first three repeats of Drosophila
      and vertebrates. Acquisition of new introns in vertebrates is supposed taking
      into account that exon borders are not found at homologous locations in four
      repeats of a given vertebrate annexin. Transcription of the annexin gene was
      detected in embryonic cell cultures. No profound effects of ecdysterone on the
      annexin X message content in cell cultures were observed.

PMID- 7710692
TI  - [Child mortality rates: a bilingual terminology review].

PMID- 7710693
TI  - Exploiting the informativity of 'meaningless' simple repetitive DNA from indirect
      gene diagnosis to multilocus genome scanning.
AB  - Most eukaryotic genomes are characterized by excessively large amounts of non
      coding DNA sequences among which redundant (repetitive) elements constitute a
      sizable portion. The functional role of an abundant subclass of repetitive
      sequences--simple, tandemly arranged repeats--remained mysterious so far. Even
      the biological meaning of most of these elements appears quite refractory to
      present-day techniques in molecular genetics. Notwithstanding simple repetitive
      sequences have been developed into superb tools for various aspects of eukaryotic
      genome research: Using oligonucleotide probes carrying simple repeat motifs
      multilocus DNA fingerprinting can be applied for individual identification and
      genetic relationship analyses in plants, animals and humans. Microsatellite
      analyses via polymerase chain reaction of simple repeat blocks allow for
      efficient investigations of such divers subject matters as criminal stains,
      detailed genome maps and indirect gene diagnoses.

PMID- 7710694
TI  - Cicadas contain novel members of the AKH/RPCH family peptides with
      hypertrehalosaemic activity.
AB  - Two new members of the adipokinetic hormone/red pigment-concentrating hormone
      (AKH/RPCH) family of peptides were identified in the cicadas Platypleura capensis
      and Munza trimeni using heterologous (in migratory locusts and cockroaches) and
      homologous (in P. capensis) bioassays. The two peptides were isolated from the
      corpora cardiaca of the two cicada species by reversed-phase high performance
      liquid chromatography. Edman sequencing after deblocking the N-terminal 5
      oxopyrrolidine-2-carboxylic acid residue revealed that both peptides have the
      amino acid sequence (pGlu)-Val-Asn-Phe-Ser-Pro-Ser-Trp-Gly-Asn. Mass
      spectrometry, however, showed that peptide 1 (eluting first on HPLC) had a mass
      352 Dalton higher than peptide 2; the exact modification of peptide 1 is not
      known yet. The N- and C-terminal blocked decapeptide 2 was synthesised and shown
      to be chromatographically indistinguishable from the natural compound under
      various HPLC conditions. Because this synthetic peptide increases the
      carbohydrate concentration in the haemolymph of P. capensis when injected, it is
      named Plc-HrTH-II, Platypleura capensis hypertrehalosaemic hormone II. Flight
      experiments with P. capensis confirmed that this species uses carbohydrates for
      flight: glycogen in the flight muscle and carbohydrates in the blood decreased by
      70% and 40%, respectively.

PMID- 7710695
TI  - Expression of two proopiomelanocortin mRNAs in the islets of Langerhans of
      neonatal rats.
AB  - Proopiomelanocortin-(POMC) derived peptides have been found in pituitary and in
      nonpituitary tissues including the endocrine pancreas. However, only a truncated
      800-base POMC-like mRNA is demonstrable in most nonpituitary tissues. The
      functional relevance of this RNA is doubtful, because it lacks the sequences of
      translation initiation and signal peptide (exon 1 and 2). Recently we have
      demonstrated the truncated POMC-like mRNA in pancreatic islets. Using PCR
      techniques in this paper we prove the existence of a full-length POMC mRNA in
      this tissue. This RNA contains the sequences of exon 1 and 2, as shown by
      Southern blot technique and by sequencing parts of the PCR products. We suppose
      that this RNA is the source of the POMC peptides in islets despite of its small
      amount.

PMID- 7710696
TI  - Cocaine exposure induces changes in the ganglioside content of rat liver.
AB  - During cocaine exposure, the liver undergoes significant morphological and
      biochemical changes. We report here changes in the ganglioside pattern of rat
      liver after repeated administration (over 5 hours, one injection per hour) of a
      moderate dose of cocaine (10 mg/kg body weight). Cocaine exposure results in an
      accumulation of more complex gangliosides (GM1, GD1a, GD1b, GT1b and GQ1b) and a
      reduction of precursors (GM3, GM2, GD3 and GD2). Our results suggest that
      ganglioside biosynthesis could be affected by an alteration of vesicular
      transport from cis- to trans-Golgi cisternae produced either by cocaine itself or
      by some product of cocaine metabolism.

PMID- 7710697
TI  - Purification of meprin from human kidney and its role in parathyroid hormone
      degradation.
AB  - Meprin (EC 3.4.24.18) is known to occur in the kidneys of mice and rats, but has
      not previously been found in human kidneys. Here we report the isolation of
      meprin from human kidney and show that it has a role in the degradation of
      parathyroid hormone (PTH) in that organ. The purified human meprin had properties
      almost identical to those of rat meprin including molecular size, substrate
      specificity and inhibitor sensitivity, and it also cross-reacted well with an
      antibody raised against rat meprin. Both the purified human meprin and the
      microvillar membranes of human kidney readily hydrolyzed human parathyroid
      hormone [hPTH-(1-84)] into several fragments, whose amino acid sequences
      corresponded well to each other. Thus, meprin appears to play a major role in the
      PTH-degrading activity in the microvillar membranes of human kidney. Our results
      indicate that meprin, which so far has mainly been investigated in mice and rats,
      is found not only in these rodents, but also in the human kidney, and suggest
      that its physiological role in humans is to degrade PTH in the kidney.

PMID- 7710698
TI  - Enzymatic peptide synthesis in frozen aqueous systems: influence of modified
      reaction conditions on the peptide yield.
AB  - The alpha-chymotrypsin (EC 3.4.21.1)-catalyzed reaction of Mal-Phe-OMe with H-Leu
      NH2 has been studied under a range of reaction conditions, for example various
      cryogenic reagents for shock-freezing, addition of dimethyl sulfoxide (DMSO) and
      decreased reaction temperatures down to 213 K. It has been shown that the peptide
      yield is independent of the method of shock-freezing. The optimal reaction
      temperature was between 263 K and 248 K. Lower temperatures result in clearly
      retarded reactions. Addition of DMSO leads to decreasing peptide yields. It is
      certain that the peptide bond formation is catalyzed by the active enzyme, since
      unspecific protein surface catalysis gave no peptide yields at all.

PMID- 7710699
TI  - Interaction of the soybean (Glycine max) seed lectin with components of the
      soybean protein body membrane.
AB  - In Leguminosae, lectins occur in the protein bodies which are membrane-lined
      storage organelles. Studies of the interaction between lectins and other protein
      body components could provide information about the internal organization of
      protein bodies and give indication of the biological function of lectins. From
      soybean (Glycine max) seeds, protein bodies and protein body membranes therefrom
      were isolated. By a technique similar to the ELISA procedure, it was shown that
      the membranes interact with the soybean lectin, SBA. This interaction can be
      inhibited by the haptenic monosaccharides specific for SBA, galactose and N
      acetylgalactosamine, and is dependent on pH and ionic strength. By thin layer
      chromatography and lecting specific staining, it was shown that lipids from the
      protein body membrane are SBA-reactive.

PMID- 7710700
TI  - Expression in Escherichia coli of rat neurotensin receptor fused to membrane
      proteins from the membrane-containing bacteriophage PRD1.
AB  - Bacteriophage PRD1 is a membrane-containing phage which could be used for
      expression of foreign membrane proteins such as neurotensin receptor (NTR), a
      seven-helix G-protein coupled receptor. To ensure recognition of NTR by the phage
      system six different fusion genes were constructed, each encoding a different
      phage integral membrane protein fused to the N-terminus of NTR, and expression of
      the fusion proteins in Escherichia coli was analysed. Here we report the
      identification of two fusion constructs that retained the function of NTR in E.
      coli. This provides the basis to develop the phage system as a heterologous
      expression system for seven-helix receptors.

PMID- 7710701
TI  - Mitochondrial DNA sequences from Switzerland reveal striking homogeneity of
      European populations.
AB  - Mitochondrial DNA sequences from 74 Swiss individuals were compared to sequences
      from British and Finish populations. We found that the nucleotide sequence
      differences between these populations are almost as low as those within the
      populations. This is in contrast to three African populations, which display
      substantial differences between each other. The homogeneity of the mitochondrial
      gene pool in Europe suggests a recent common ancestry for European populations.
      This may reflect the arrival of anatomically modern humans about 40,000-30,000
      years ago or, alternatively, the spread of agriculturalists about 10,000-6,000
      years ago. Taking into account the estimated rate of evolution of the
      mitochondrial control region, the data favor the former explanation.

PMID- 7710702
TI  - Effects of inorganic phosphorus compounds on the hydrolysis of
      phosphatidylcholine liposomes by phospholipid-deacylating enzymes.
AB  - Structural requirements of inorganic phosphorus compounds as specific activators
      or inhibitors for phospholipase A2 and phospholipase B were investigated using
      orthophosphate, pyrophosphate and polyphosphate. It was observed that
      orthophosphate and pyrophosphate stimulated the activities of phospholipase A2
      from bee venom, snake (Naja naja) venom and pig pancreas, and also phospholipase
      B from the yeast Torulaspora delbrueckii. However, polyphosphate was found to act
      as an inhibitor for phospholipase A2 in the above species and also for
      phospholipase B from T. delbrueckii. Orthophosphate and pyrophosphate induced
      gradual aggregation of liposome, but polyphosphate prolonged the lifetime of the
      liposome, suggesting that orthophosphate and pyrophosphate destabilize the
      bilayer structure of phosphatidylcholine and polyphosphate stabilizes it.

PMID- 7710703
TI  - Yeast-prepro-alpha-factor-leader-region-directed synthesis and secretion of
      truncated human macrophage colony-stimulating factor in the silkworm Bombyx mori.
AB  - Human macrophage colony-stimulating factor (hM-CSF) cDNA joined to the leader
      region of the precursor of the yeast mating pheromone alpha-factor (MF alpha L)
      was expressed at high levels in BmN cells and in silkworm (Bombyx mori) larvae,
      using recombinant Bombyx mori nuclear polyhedrosis virus, as a vector. The
      biological activity of rhM-CSF detected in the haemolymph was 1 x 10(6) colony
      formation units/ml, approximately half of the expression level directed by the
      native signal peptide of hM-CSF in silkworm larvae. The secreted rhM-CSF was
      purified to homogeneity. N-terminal analysis showed that the signal peptide had
      been removed, indicating that insect cells possess the enzymic activity necessary
      to cleave the pro-alpha-factor leader region from the fusion protein at the
      carboxy side of Lys-Arg dibasic residues, which is the cleavage site recognized
      by KEX2 endopeptidase in yeast cells.

PMID- 7710704
TI  - The development of a purification procedure for saxitoxin-induced protein.
AB  - A simple economical procedure for purifying saxitoxin-induced protein (SIP) from
      crude extracts of the small shore crab, Hemigrapsus oregenesis, was developed.
      (NH4)2SO4 precipitation, chymotrypsin digestion, heat treatment, gel filtration
      and ion-exchange-chromatography procedures were evaluated in purifying SIP. An
      enzyme immunoassay was used to determine the SIP yield and relative purity at
      each step of three procedures, thus permitting an assessment of the conditions
      required for maximum recovery. Response surface analysis was used in an attempt
      to determine the optimum temperature and exposure time for the heat treatment. A
      20 min incubation at 65 degrees C was confirmed by electrophoretic analysis to be
      the best combination of time and temperature for achieving both an acceptable
      yield and purity of SIP. SIP in desalted concentrate was shown to be resistant to
      chymotrypsin proteolysis; however, this enzyme had deleterious effects on SIP
      purification at later stages of the procedure. The omission of the chymotrypsin
      digestion, and the inclusion of gel-filtration chromatography in the final clean
      up step, resulted in the purification of SIP comparable with that achieved with
      affinity chromatography.

PMID- 7710705
TI  - The macroheterogeneity of recombinant human interferon-gamma produced by Chinese
      hamster ovary cells is affected by the protein and lipid content of the culture
      medium.
AB  - The culture environment exerts a major effect on the glycosylation pattern of
      recombinant human interferon-gamma (IFN-gamma) produced by Chinese-hamster ovary
      (CHO) cells. The recombinant IFN-gamma is heterogeneous and consists of a mixture
      of fully (2N), partially (1N) and non-glycosylated (0N) glycoforms, and
      throughout batch cultures there is a decline in the proportion of fully
      glycosylated IFN-gamma. Glucose and glutamine, nutrients that are depleted early
      in such cultures, were prima facie candidates for causing such a shift in
      glycoform profile. Batch feeding of these nutrients did not prevent the decline
      in 2N glycoform, but the glycosylation pattern of IFN-gamma was affected by the
      initial glutamine concentration in the culture. Under different serum-free
      environments the extent of IFN-gamma glycosylation was affected by (1) the
      concentration of BSA, (2) the quality of BSA, (3) the lipid composition of the
      culture medium and (4) the presence of surfactants. Moreover, the inclusion of
      serum in cultures caused changes in the molecular masses of the major glycoforms,
      that was indicative of cleavage of the core polypeptide. The results reported
      emphasize the necessity of considering the effects of culture media on product
      quality as well as on product quantity during process optimization.

PMID- 7710706
TI  - Atopic allergy and other hypersensitivities.

PMID- 7710707
TI  - Regulation of the development of type 2 T-helper cells in allergy.
AB  - In the last few years evidence has been accumulated to suggest that allergen
      reactive type 2 T helper (Th2) cells play a triggering role in the activation
      and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils,
      the cellular triad involved in the allergic inflammation. Interleukin (IL)-4
      production by a still unknown cell type (T-cell subset, mast cell/basophil?) at
      the time of antigen presentation to the Th cell is critical for the development
      of Th2 cells. Other cytokines, such as IL-1 and IL-10, and hormones, such as
      calcitriol and progesterone, also play a favoring role. In contrast, cytokines
      such as interferon-alpha, interferon-gamma, IL-12 and transforming growth factor
      beta, and hormones, such as dehydroepiandrostenone, play a negative regulatory
      role in the development of Th2 cells. However, the mechanisms underlying the
      preferential activation by environmental allergens of Th2 cells in atopic
      subjects still remain obscure. Among the possibilities are alterations to
      molecular mechanisms directly involved in the regulation of IL-4 gene expression
      or deficient regulatory activity of cytokines that antagonize Th2 cells.

PMID- 7710708
TI  - Induction of non-responsiveness in human allergen-specific type 2 T helper cells.
AB  - Activation of allergen-reactive human T helper (Th)2 cells in the absence of
      professional antigen-presenting cells, induces non-responsiveness or anergy in
      these cells in vitro. This induction of anergy is accompanied by phenotypic
      modulation and altered cytokine production. Furthermore, peptide-treated Th2
      cells fail to provide B-cell help for IgE synthesis. Recent studies indicate that
      impaired signal transduction via the T-cell receptor may account for the lack of
      responsiveness to antigenic stimulation. Here, we review present knowledge on the
      cell biology of non-responsive or anergic Th2 cells.

PMID- 7710709
TI  - The role of mast cells in inflammatory reactions of the airways, skin and
      intestine.
AB  - The concept that mast cells play a key role in the initiation of acute allergic
      responses has been around for many years. However, the role of mast cells in the
      chronic processes that are the hallmark of inflammatory disease is still poorly
      understood. With better techniques to study mast cell function it has become
      clear that these cells may have a much wider role in immune responses and
      regulation than previously recognized. Exciting progress has been made over the
      past year in defining the breadth of mast cell functions in inflammation. Further
      studies are necessary to evaluate the in vivo significance of many of these
      findings.

PMID- 7710710
TI  - The role of eosinophils in the pathogenesis of asthma.
AB  - The eosinophil is regarded as a key mediator of the pathology and abnormal
      physiology of bronchial asthma. Current investigations are directed at
      understanding how eosinophils are attracted into the respiratory tract and how
      they bring about the abnormalities characteristic of this disease.

PMID- 7710711
TI  - Chemokines, leukocyte trafficking, and inflammation.
AB  - The relatively recent appreciation of a new class of cytokines, the chemokines,
      has done much to enhance our understanding of the extracellular signals involved
      in the movement of various populations of white blood cells. Investigation of the
      molecular underpinnings of chemokine function and their involvement in
      inflammatory processes of all kinds is beginning to yield information about the
      mechanisms of pathogenesis of a number of conditions, as well as providing hope
      for new therapeutic insights.

PMID- 7710712
TI  - Mechanisms of autoimmunization: perspective from the mid-90s.

PMID- 7710713
TI  - T-cell tolerance and autoimmunity in transgenic models of central and peripheral
      tolerance.
AB  - Experiments with transgenic mice expressing genes encoding both antigens in
      defined tissues and T-cell receptor genes of known specificities have enhanced
      our understanding of the mechanisms involved in the pathogenesis of autoimmune
      states. They have also shed light on the means by which potentially autoreactive
      cells may be prevented from exerting their autoaggressive potential. The value of
      the transgenic approach is that it can overcome the low frequency of peptide
      specific T cells occurring in normal animals, and also provide a tissue-specific,
      cognate antigen that is absent in controls. These factors allow reactive T cells
      to be isolated or quantified by flow cytometry and their responses to antigen in
      vitro and in vivo be defined.

PMID- 7710714
TI  - Genetic and pathogenic basis of autoimmune diabetes in NOD mice.
AB  - Non-obese diabetic (NOD) mice are an excellent model of T-cell mediated
      autoimmune insulin-dependent diabetes in humans. Recent studies in NOD mice have
      shown that this disease is a result of epistatic interactions between multiple
      genes, both inside and outside the major histocompatibility complex (MHC),
      generating T cells reactive against an expanding repertoire of autoantigens.

PMID- 7710715
TI  - How unique are pathogenic anti-DNA autoantibody V regions?
AB  - Unique characteristics of the molecular structure of V regions encoding
      pathogenic anti-DNA autoantibodies have become apparent upon comparison of a
      large number of nucleotide sequences encoding this autospecificity. Moreover, the
      generation of transgenic animals expressing V regions encoding anti-DNA
      autoantibodies has shed light on the tolerizing mechanisms that regulate B cells
      producing antibodies against DNA.

PMID- 7710716
TI  - Autoimmune hemolytic anemia.
AB  - Autoimmune hemolytic anemia (AHA) is characterized by the production of Coombs'
      antibodies, which are responsible for the destruction of red blood cells (RBCs).
      Analysis of both monoclonal anti-RBC autoantibodies derived from autoimmune New
      Zealand black mice and transgenic mice expressing a pathogenic IgM anti-RBC
      autoantibody has considerably improved our understanding of the B-cell responses
      involved in AHA, although our knowledge of T-cell immunity in AHA is still
      limited. The identification of the major T-cell epitope in the context of MHC
      class II molecules would be of paramount importance in helping to elucidate the
      cellular and molecular basis central to the development of AHA.

PMID- 7710717
TI  - Autoantibodies in scleroderma and tightskin mice.
AB  - There is much evidence to suggest that scleroderma in human patients is caused by
      a fundamental defect in the immune system. In tightskin mice, the scleroderma
      syndrome is associated with autoimmunity, particularly autoantibodies interacting
      with scleroderma target antigens.

PMID- 7710718
TI  - Autoimmunity in the eye and its regulation.
AB  - Recent studies have provided new information concerning the development of
      autoimmune-mediated intraocular inflammation (uveitis) and the mechanisms that
      suppress this sight-robbing process. Newly collected data have led to several
      interesting advances: the discovery of additional uveitogenic antigens and novel
      uveitogenic reactions; dissection of the early steps of the pathogenic process;
      identification of the subsets of lymphocytes that selectively accumulate in the
      inflamed eye; analysis of the development of tolerance against sequestered
      antigens in the eye; elucidation of the cellular and molecular events of the
      anterior chamber-associated immune deviation, the major immunoregulatory
      mechanism in the eye; the capacity of this mechanism to inhibit and even treat
      uveitis; and examination of the mechanisms whereby oral tolerance inhibits ocular
      inflammation.

PMID- 7710719
TI  - Regulation of autoimmune response.
AB  - Recent work on such apparently disparate fields as T-cell receptor peptide
      induced regulation, superantigens, antigen-induced tolerance, models of
      peripheral tolerance, apoptosis, and T-cell receptor antagonists demonstrates a
      similarity in immune response from a regulatory perspective. In many systems, a
      'tolerance' pathway is observed, characterized broadly as an initial disturbance
      in the immune system, with a resulting predominance of effector cells, followed
      by a homeostatic response (often requiring CD8+ cells) which leads the effector
      population into T-cell receptor downregulation, T-cell inactivation, anergy and,
      often, eventual apoptotic death. In the regulated immune response, mixed
      populations of anergized and apoptosing T cells can be found. In some cases,
      anergy appears to lead to death while, in other instances, cells revert to a
      functional state. This review focuses on recent papers examining each of these
      topics in an attempt to obtain a preliminary integrated picture of immune
      regulation in autoimmune diseases.

PMID- 7710721
TI  - Autoimmunity.

PMID- 7710720
TI  - Atopic allergy and other hypersensitivities.

PMID- 7710722
TI  - Comparison of multiple frequency vibrometry testing and sensory nerve conduction
      measures in screening for carpal tunnel syndrome in an industrial setting.
AB  - The value of vibrometry in the evaluation of carpal tunnel syndrome is
      controversial. Several investigators have suggested that vibrometry screening
      with multiple frequencies would improve the correlation and increase the
      sensitivity when screening for carpal tunnel syndrome. One hundred sixty-nine
      industrial workers from two manufacturing plants in southern Michigan were
      screened for median nerve impairment using both vibrometry (seven frequencies, 8
      500 Hz) and electrophysiologic testing in each hand. The vibratory threshold at
      each frequency, as well as composite measures-Jetzer index and negative sums,
      were compared with electrophysiologic measures of amplitude and latency. The
      individual frequencies and the Jetzer index correlated with median sensory
      latency, but the relationships were weak (r = 0.22 to 0.32). Only at the lower
      frequencies (8, 16, and 32 Hz) did the vibratory threshold correlate with sensory
      amplitude; correlation ranged from 0.187 to 0.303. Vibration threshold sensation
      is most closely related to axonal loss or conduction block, but the earliest
      finding in carpal tunnel syndrome is that of demyelination; thus we would not
      expect an abnormal vibratory threshold with mild carpal tunnel syndrome. These
      results support this interpretation and suggest that vibratory screening for
      early carpal tunnel syndrome is not effective.

PMID- 7710723
TI  - Functional assessment scales. A study of persons after traumatic brain injury.
AB  - The purpose of this study was to investigate disability in persons after
      traumatic brain injury (TBI) by using combinations of functional assessment item,
      subscale, domain, and full-scale scores to predict (1) the need for assistance in
      performance of specific physical care tasks measured in minutes of help per day
      provided by another person in the home and (2) the subject's level of
      satisfaction with life in general. This study also sought to account for the
      amount of supervision that persons with TBI may require beyond that needed for
      physical care tasks. The Functional Independence Measure (FIM) contributed to
      prediction of subjects' physical care needs. A single-point change in total FIM
      score was equivalent to an average of about 5 min of help from another person per
      day. Satisfaction with life in general was predicted mainly by the depression
      subscale of the Brief Symptom Inventory. However, this latter prediction was only
      true when subjects who required constant supervision were removed from analysis.
      Thus, the amount of supervision required by persons with TBI is an important
      variable to study in this population. Three categories of supervision were
      identified: constant (all of the time), periodic (daily or weekly), or not at
      all. The need for supervision and physical assistance from another person and a
      subject's satisfaction with life in general are important standards by which
      functional assessment instruments may be compared to reflect, in pragmatic terms,
      the impact of disability on the lives of individuals and on human and economic
      resources of the community.

PMID- 7710724
TI  - Occurrence of fever associated with thermoregulatory dysfunction after acute
      traumatic spinal cord injury.
AB  - The medical records of 156 patients with acute traumatic Spinal Cord Injury
      (SCI), admitted for inpatient SCI rehabilitation during the period from January
      1, 1990 through December 31, 1992, were retrospectively reviewed. Seventy-one
      patients with acute traumatic SCI were identified at risk for thermoregulatory
      dysfunction (50 patients with cervical SCI and 21 with upper thoracic level SCI).
      A total of 713 days were documented in which febrile events occurred in 60 of 71
      patients during the study period. Over 39% of these fevers measured 101 degrees F
      (38.3 degrees C) or greater. There were 71 days of documented febrile episodes
      occurring in 17 patients for which an etiology could not be determined. Fifteen
      of these individuals had fewer than five such febrile days each during their
      entire rehabilitation hospitalization. Study results indicate that in a
      population of patients with acute traumatic SCI at risk for thermoregulatory
      dysfunction, the occurrence of fever is quite high. Fever not attributable to
      infectious or inflammatory etiologies is uncommon. Fever attributable to
      thermoregulatory dysfunction in this setting should be considered only after
      other etiologies have been carefully excluded.

PMID- 7710725
TI  - Therapeutic exercise in the prevention of bone loss. A controlled trial with
      women after menopause.
AB  - To evaluate the efficacy of therapeutic exercises in the prevention of bone loss,
      146 untrained healthy postmenopausal women were prospectively controlled for
      (mean +/- SD) 3.0 +/- 1.3 yr. Eighty-two subjects aged (mean +/- SD) 61.5 +/- 6.1
      yr participated in an exercise program (group 1) and sixty-four aged (mean +/-
      SD) 59.1 +/- 7.4 yr served as controls (group 2). Periodically during the study
      period, we measured women's bone density at two forearm sites and recorded their
      physical activities. Because bone loss differed insignificantly between the
      groups, group 1 was retrospectively subdivided into group 1a (regular exercise)
      and group 1b (nonregular exercise). The results showed that only 39 women (48
      percent) of group 1 (group 1a) performed the exercise program regularly for the
      prescribed time. Regression slopes of forearm bone density (distal and proximal
      scans) v time were significantly less negative (P < 0.05) in group 1a (distal, 
      0.3 percent and proximal, -0.7 percent per year) than in group 1b (distal, -1.8
      percent and proximal -1.6 percent per year) or group 2 (distal, -1.7 percent and
      proximal, -1.9 percent per year). We conclude that in untrained elderly women,
      poor compliance with regular physical activities is a main factor, explaining the
      lack of response to exercise treatment in prevention of osteoporosis.

PMID- 7710726
TI  - The value of special motor and sensory tests for the diagnosis of benign and
      minor median nerve lesion at the wrist.
AB  - Four special tests to assess benign and minor median nerve lesion at the wrist
      (MLW) were evaluated in 40 controls and three groups of 25 carpal tunnel syndrome
      with different degrees of orthodromic sensory conduction velocity (OSCV) slowing.
      The motor tests were the median-ulnar distal latency difference of the thenar
      muscles and the second lumbrical-interossei distal latency difference. They were
      abnormal in only 20% and 4% of patients, respectively, in group 1 (OSCV > 45
      m/s), in 56% and 60% in group 2 (45 m/s > OSCV > 40 m/s), and were both abnormal
      in 96% of patients in group 3 (OSCV < 40 m/s). The two sensory tests were the
      median-ulnar orthodromic sensory latency difference of the fourth digit and the
      centimetric technique; they were abnormal in 80% and 96% (group 1) and in 96 and
      100%, respectively (group 2). All things considered, only the sensory tests
      showed a satisfactory efficacy to assess benign and minor MLW, because the motor
      tests reached a positivity of 96% only in group 3.

PMID- 7710727
TI  - Anatomic sites of foot lesions resulting in amputation among diabetics and non
      diabetics.
AB  - OBJECTIVE: To identify and quantify the anatomic sites of foot lesions resulting
      in amputation among patients suffering from peripheral arterial disease with and
      without diabetes mellitus. DESIGN: A retrospective study. SETTING: Department of
      Orthopaedic Rehabilitation. PATIENTS: A total of 212 recent lower limb amputees
      with diabetes mellitus (158) or peripheral arterial disease only (54) admitted
      for prosthetic rehabilitation. RESULTS: In 62.2% of all amputees the site of
      lesion that led to amputation was located in the digits. A lesion under the
      metatarsal heads was reported in 8.0%, along the mid-foot and heel in 8.5%, on
      the dorsum of the foot in 3.3%, around the ankle joint and lower leg in 5.7%.
      Finally, 12.3% reported multiple lesions or were unable to recall the exact
      anatomic location. CONCLUSIONS: Most foot lesions resulting in amputation are
      located around the digits. These high-risk sites, therefore, need the patient's
      and the health care team's special attention. The patient should be trained in
      self foot examination and meticulous daily care, whereas the role of the health
      care team is in foot evaluation and provision of protective foot wear.

PMID- 7710728
TI  - Replantation and amputation of digits: user analysis.
AB  - There now is extensive literature on the survival and function of replanted
      digits but little on the function of the hand as a whole after this procedure, as
      opposed to amputations. In our review of the literature, we found almost nothing
      on the patient's perspective of the outcome from these procedures. This study was
      a preliminary attempt to study the outcome of these procedures from the patient's
      viewpoint. There were nine replantations and ten amputations of digits in the
      final study groups, based on medical record screening and patient questionnaires.
      Multivariate analysis, Hotelling T2, was used to test significant differences
      between the variables in the two groups. Significant differences were found in
      the two groups. The replantations had longer lengths of treatment and therapy,
      were off work longer (34.4 wk of therapy and 40 wk off work), and rated their
      function poorer compared with amputations. The patients with digit amputations
      had 7.2 wk of therapy and lost 6.8 wk of work. Ninety percent of the amputees
      rated their function as good or excellent, in contrast to 44.4% of the
      replantation patients. These findings are supported by existing literature that
      suggests that single-digit replants do not help with function of the whole hand,
      which is the therapeutic aim.

PMID- 7710729
TI  - Flexion-relaxation phenomenon in the back muscles. A comparative study between
      healthy subjects and patients with chronic low back pain.
AB  - At a certain position of trunk flexion, there is a sudden onset of electrical
      silence in back muscles. This is called "flexion-relaxation (F-R) phenomenon."
      The goals of this study were (1) to evaluate the relationship between flexion
      angle and activity of back muscles during flexion movement and (2) to determine
      what the difference is between healthy subjects and patients with chronic low
      back pain (CLBP). Twenty-five healthy subjects (13 males and 12 females; average
      age, 28.3 yr) and 20 patients with CLBP (12 males and 8 females; average age,
      34.1 yr) volunteered for this study. The subjects were asked to flex forward
      maximally from the erect position and to maintain full flexion, followed by
      returning to the initial upright position. Flexion angle of trunk and hip was
      measured during the examination. Electromyographic activity of erector spinae was
      also monitored simultaneously. F-R phenomenon was observed in all healthy
      subjects before reaching the maximum flexion. Electrical silence continued even
      after extending the trunk began. In contrast, no patients with CLBP demonstrated
      F-R phenomenon. A significant difference in muscular activities of erector spinae
      between the groups was obtained when returning to the erect position from the
      maximum flexion. Moreover, time lag between trunk and hip movement was much
      greater in patients than in healthy subjects. This study demonstrated that
      neuromuscular coordination between trunk and hip could be abnormal in patients
      with CLBP.

PMID- 7710730
TI  - Common questions asked by medical students about physiatry. Brief report.
AB  - This article was prepared by physiatry residency training directors to provide
      the answer(s) to common questions asked by medical students with respect to the
      specialty. These responses should aid the student and their advisors in
      considering Physical Medicine and Rehabilitation as their career choice.

PMID- 7710731
TI  - Psychogenic cough treated with biofeedback and psychotherapy. A review and case
      report.
AB  - Psychogenic cough is a barking or honking cough, which is persistent and
      disruptive to normal activity. The cough may be a debilitating condition that
      interferes with work and social relationships. Although the frequency of this
      condition is low, it is not rare. The majority of cases reported involve
      pediatric or adolescent patients. Surprisingly, there are scant data describing
      this condition in the adult population and no reports of biofeedback being used
      to treat this syndrome. We present a case report of an adult patient with
      psychogenic cough and review the available pediatric and adult literature. A 41
      yr-old obese female presented with a complex 7-yr history of intractable,
      nonproductive, chronic cough. She had been avoiding social activities because of
      embarrassment by her repeated episodes of coughing. Extensive diagnostic work-up
      failed to find an organic etiology. Numerous medical and surgical treatments had
      failed. The patient was treated with a combination of biofeedback-assisted
      relaxation training, psychotherapy, and physical therapy. Review of the
      literature revealed only one report on adults, in which three of four patients
      were successfully treated with a combination of speech therapy, relaxation
      techniques, breathing exercises, and psychotherapy. Our success suggests a
      possible future use of this treatment protocol for cases of psychogenic cough.

PMID- 7710732
TI  - Challenges for academic physiatry in the era of health care reform. A commentary.

PMID- 7710733
TI  - Fellowship training in physical medicine and rehabilitation. Developed by the
      Association of Academic Physiatrists.
AB  - The AAP supports the development of fellowships, especially those that enhance
      research in areas relevant to PM&R. If possible, research training within
      fellowship programs should be acknowledged. As accredited fellowships develop,
      the AAP acknowledges potential risks to residency training and supports
      accreditation standards that consider the importance of coexisting fellowships
      and residency programs.

PMID- 7710734
TI  - Analysis of stage-sequential change in rehabilitation research.
AB  - The analysis of change is a critical topic for rehabilitation outcomes research,
      because the goal of rehabilitation is to improve patients' function. This article
      will sketch the issues and problems in statistical methods for analysis of
      change. Recovery after serious illness or injury often has been described in
      terms of transitions between a series of stages, but these theories of recovery
      have rarely been subjected to adequate statistical examination. This article
      presents two methods for the analysis of change, suitable for ordinal measures of
      function and for testing either simple cumulative or complex multipath stage
      models of recovery. Progress in medical rehabilitation will be enhanced by
      explicitly specifying models of recovery, measuring recovery at multiple time
      points, and using the resulting data to test these models empirically.

PMID- 7710735
TI  - Resident versus program director perceptions about PM&R research training.
AB  - A survey of all residents and residency program directors in Physical Medicine
      and Rehabilitation (PM&R) was done to assess perspectives of residents and
      directors regarding research training, resources, mentorship, and encouragement
      available to residents. A response rate of 55% was obtained from 1188 resident
      mailings, and 83% of 77 program directors responded. A number of discrepancies in
      perceptions of residents v program directors responded. A number of discrepancies
      in perceptions of residents v program directors were identified. In general,
      residents perceived that they had less research support and training than
      directors felt their departments were offering. Only 24% of residents felt that
      they got adequate training in statistics, 40% for research design, and 26% for
      writing research papers. The corresponding numbers for residency program
      directors were 47%, 73%, and 61%. There were similar discrepancies in the
      perception of the quality of research training. On a 1 to 5 scale, residents
      registered a mean score of 2.8 (SD 1.0) to the question of how qualified their
      faculty was to teach principles of research. Program directors' mean response was
      3.2 (SD 1.0). Residents were also often not aware of resources available for
      research in their departments. Only 19% of residents knew of access to a research
      coordinator/grant writer, 36% for statistical support, and 67% for library
      assistance. The corresponding numbers for program directors were 31%, 69%, and
      97%. Additional results of the survey are summarized, and suggestions for further
      study to improve the resident research training experience are given.

PMID- 7710736
TI  - MKC-231, a choline uptake enhancer, ameliorates working memory deficits and
      decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in
      mice.
AB  - The effects of acute and chronic administration of MKC-231, a new choline uptake
      enhancer, and two other nootropic agents, linopiridine (Dup 996) and
      tetrahydroaminoacridine (THA) on working memory deficits and decreased
      hippocampal acetylcholine (ACh) content were studied in a delayed non-matching to
      sample task, using a T-maze, in ethylcholine aziridinium ion (AF64A)-treated
      mice. Treatment with AF64A (3.5 nmol, i.c.v.) produced memory deficits and
      decreased hippocampal ACh content. In acute behavioral experiments, MKC-231 and
      THA had no significant effect on AF64A-induced memory deficits at any doses
      tested (0.3, 1.0 and 3.0 mg/kg), whereas Dup 996, at a dose of 1.0 mg/kg,
      significantly improved memory deficits. In chronic experiments, MKC-231 improved
      memory deficit at all doses tested (0.3, 1.0, or 3.0 mg/kg p.o., once daily for
      11 days) and Dup 996 did so only at a dose of 3.0 mg/kg, whereas THA did not
      improve memory deficit at any doses tested. In acute neurochemical experiments,
      MKC-231 and THA did not reverse the AF64A-induced hippocampal ACh depletion. Dup
      996, however, further decreased hippocampal ACh content compared to that in the
      AF64A-treated group. In chronic experiments, MKC-231 significantly reversed
      hippocampal ACh depletion at doses of 0.3 and 1.0 mg/kg, whereas neither Dup 996
      nor THA reversed hippocampal ACh depletion at any doses tested. These results
      indicate that MKC-231 improved the AF64A-induced working memory deficit and
      hippocampal ACh depletion, probably by recovering reduced high-affinity choline
      uptake and ACh release.

PMID- 7710737
TI  - Nefiracetam enhances acetylcholine outflow from the frontal cortex: in vivo
      microdialysis study in the rat.
AB  - The effects of nefiracetam [DM-9384; N-(2, 6-dimethylphenyl)-2-(2-oxo-1
      pyrrolidinyl)acetamide], a cognitive enhancer, on extracellular acetylcholine and
      glutamic acid in the frontal cortex were studied using brain microdialysis in
      freely moving rats. Nefiracetam administration (1 mg/kg, p.o.) doubled the amount
      of acetylcholine in the dialysate. When tetrodotoxin was added to the perfusion
      solution, the basal level of acetylcholine decreased and nefiracetam caused no
      increase in acetylcholine outflow. The amount of glutamic acid in the dialysates
      was not affected by nefiracetam. These results suggest that nefiracetam increases
      the amount of acetylcholine within the cholinergic synaptic clefts.

PMID- 7710738
TI  - Differential effects of dopamine D2 and D3 receptor antagonists in regard to
      dopamine release, in vivo receptor displacement and behaviour.
AB  - To establish possible functional differences between the dopamine D2 and D3
      receptor we investigated the relation between the ability, for a set of nine
      mixed dopamine D2 and D3 receptor antagonists, to displace N, N-dipropyl-2-amino
      5,6-dihydroxy tetralin (DP-5,6-ADTN) from striatal binding sites and the
      subsequent behavioural consequences in vivo. Dopamine D2 receptor preferring
      antagonists are powerful displacers of DP-5,6-ADTN from the striatum. Maximal
      displacement is followed by strong hypomotility. Displacement of the agonist by
      the D3 preferring antagonist U99194A is only partial and results in synergistic
      increases in locomotor activity. Superimposing haloperidol upon GBR12909 leads to
      a synergistic increase in striatal dialysate dopamine concentrations. This effect
      is absent when combining GBR12909 with the putative D3 antagonist U99194A. These
      data give support for the hypothesis that the dopamine D3 receptor is
      functionally relevant at the postsynaptic level. Here, in contrast to the D2
      receptor, it is proposed to exert an inhibitory influence on psychomotor
      functions.

PMID- 7710739
TI  - Memantine, amantadine, and L-deprenyl potentiate the action of L-dopa in
      monoamine-depleted rats.
AB  - Some treatments used for Parkinson's disease attenuate locomotor depression in
      rats treated with reserpine and alpha-methyl-p-tyrosine. In the present study
      memantine (2.5, 5.0 mg/kg), amantadine (10, 20 mg/kg) (both uncompetitive NMDA
      antagonists), and L-deprenyl (1.0, 5.0 mg/kg; MAO-B inhibitor) were tested for
      possible synergistic interactions with the dopamine agonists: bromocriptine (2.5,
      5.0 mg/kg) and L-dopa (50, 100 mg/kg, +benserazide, 100 mg/kg). At higher doses,
      memantine (10 mg/kg), amantadine (40 mg/kg), bromocriptine (5 and 10 mg/kg) and L
      dopa (100, 200 mg/kg) but not L-deprenyl (up to 10 mg/kg) produced a pronounced
      increase in locomotor activity when given alone. The combination of memantine,
      amantadine and L-deprenyl with bromocriptine did not result in synergism of
      action and, at best, an additive effect was seen. On the other hand the
      combination of these agents with L-dopa produced a pronounced synergistic effect.
      Hence, the clinical observation that coadministration of L-dopa with either
      memantine or amantadine results in enhancement of their action is also reflected
      in an animal model of Parkinson's disease. Such a combination therapy should
      allow the use of lower doses of both drugs which may reduce the occurrence of
      side effects and may also be predicted to have additional benefits related to the
      neuroprotective properties of memantine, amantadine, and L-deprenyl.

PMID- 7710740
TI  - Increase in brain GABA-transaminase activity after chronic ethanol treatment in
      rats.
AB  - The activity of gamma-aminobutyrate aminotransferase (GABA-T) was measured in the
      brains of rats treated both acutely and sub-chronically with ethanol. Previously,
      chronic treatment with ethanol for 90 weeks was found to increase the mean brain
      GABA-T activity by 20-45%. In the present study acute ethanol treatment (4 g/kg,
      i.p.) did not induce and change in the activity of brain GABA-T with the
      exception of a small increase in the cerebellum (8%) and, after repeated
      treatment with ethanol (4 g/kg/day, i.p.) for one and two weeks, no change in the
      activity of GABA-T was also found in any of the brain regions examined.
      Subchronic treatment with ethanol for 14 weeks, performed according to two
      different schedules involving a voluntary intake of ethanol in the drinking
      water, resulted in approximately a two-fold difference in ethanol intake. A mean
      increase of 50-85% in the activity of GABA-T was found in all the brain regions
      of rats with higher ethanol intake in comparison with the group of rats with
      lower ethanol intake. A bimodal distribution of brain GABA-T activity, however,
      was found in the ethanol-treated rats, with 60% of the rats having a two-fold
      increase and the remaining 40% having unchanged activities. The addition of
      pyridoxal phosphate to the incubation media increased the activity of brain
      mitochondria from ethanol-treated rats with high brain GABA-T, whereas there was
      a decrease in the activity in control rats and in ethanol-treated rats in which
      no increase in brain GABA-T had occurred. These results show firstly, that in a
      subpopulation of rats, subchronically treated with ethanol for 14 weeks, there
      was a two-fold increase in brain GABA-T activity, while in another subgroup no
      change occurred, and, secondly, that this increase in GABA-T activity was a
      consequence of a change in the response of the apoprotein to the addition of the
      cofactor pyridoxal phosphate.

PMID- 7710741
TI  - Distribution and morphologic features of coronary artery disease in cardiac
      allografts: an intracoronary ultrasound study.
AB  - The longitudinal distribution and circumferential pattern of coronary intimal
      proliferation were studied with intravascular ultrasonography in 135 patients
      after heart transplantation. Eighty-seven (64%) of 135 patients had significant
      intimal thickening, with most lesions (63%) concentric and free of fibrosis or
      calcification. Both diffuse and nonuniform longitudinal patterns of intimal
      thickening were found.

PMID- 7710742
TI  - Echocardiographic diagnosis of pulmonary embolism in childhood.
AB  - Pulmonary embolism is a rare problem in the pediatric age group. As in adults,
      symptoms include tachypnea, chest discomfort, and hypoxia, but the index of
      suspicion in making this diagnosis in children is low. This report confirms the
      usefulness of two-dimensional and Doppler echocardiography in the diagnosis of
      pulmonary embolism, regardless of patient age. Causes of hypercoagulable states
      in children are also briefly discussed.

PMID- 7710743
TI  - Transesophageal echocardiographic imaging of misplaced ventricular pacing
      electrode.
AB  - Misplacement of pacemaker electrodes has been reported in different locations
      within the heart with divers clinical consequences. We present a patient in whom
      transesophageal echocardiography was of significant importance in imaging and
      understanding the electrode's course within the heart chambers.

PMID- 7710744
TI  - Role of echocardiography in the diagnosis and surgical management of accessory
      mitral valve tissue causing left ventricular outflow tract obstruction.
AB  - We report an unusual case of left ventricular outflow tract obstruction caused by
      accessory mitral valve tissue. This case illustrates the importance of
      transthoracic echocardiography in preoperative evaluation and the usefulness of
      transesophageal echocardiography for intraoperative assessment. If the accessory
      mitral valve has no functional significance it may be surgically excised, thereby
      relieving the outflow tract obstruction.

PMID- 7710745
TI  - Acquired left ventricular-right atrial communication caused by infective
      endocarditis detected by transesophageal echocardiography: case report and review
      of the literature.
AB  - Acquired left ventricular-right atrial communication due to infective
      endocarditis was diagnosed in a 64-year-old patient by transesophageal
      echocardiography and confirmed by cardiac catheterization. The patient was
      initially treated medically and then referred for corrective surgery.

PMID- 7710746
TI  - An analysis of the safety of performing dobutamine stress echocardiography in an
      ambulatory setting.
AB  - Dobutamine echocardiography has become widely used in the past decade in the
      evaluation of patients with suspected coronary artery disease who are unable to
      undergo exercise treadmill or bicycle testing. The safety of this procedure has
      been studied in a hospital-based setting. However, no studies thus far have
      evaluated the safety of this procedure in an office-based setting, remote from a
      hospital. We performed dobutamine echocardiography on 127 patients in an office
      based setting, remote from a hospital. Throughout the course of this study there
      were no deaths, myocardial infarctions, sustained episodes of ventricular
      tachycardia, or syncopal episodes associated with dobutamine infusion. The
      frequency of noncardiac side effects was 29%, the majority of which were nausea,
      vomiting, and paresthesias. Three patients had nonsustained ventricular
      tachycardia, none of whom had symptoms. We conclude that dobutamine
      echocardiography is safe, well tolerated, and useful in an office-based setting.

PMID- 7710747
TI  - Reliability of blood pressure, heart rate, and Doppler-derived hemodynamic
      measurements during exercise.
AB  - Doppler echocardiography of aortic blood flow, heart rate, and blood pressure
      represent noninvasive methods for evaluation of the hemodynamic effects of
      pharmacologic agents or other stimuli during rest and exercise. In this study the
      reliability of continuous-wave Doppler echocardiography for detecting the effects
      of various interventions on left ventricular systolic function during exercise
      was assessed. The reliability of Doppler measurements was compared with that
      found for measurements of simultaneously obtained heart rate and blood pressure.
      Exercise treadmill testing was performed at 0, 2, 4, 6, and 8 hours in 18 healthy
      male subjects. All measurements were performed at rest and during the last half
      of each exercise stage. Reliability of peak modal velocity, peak aortic blood
      flow acceleration, heart rate, and blood pressure was measured by the intraclass
      correlation coefficient (ICC) at each stage. ICC reliability of greater than 0.75
      is considered excellent, 0.4 to 0.75 fair to good, and less than 0.4 poor. The
      reliability of all Doppler-derived parameters, heart rate, and blood pressure
      improved with increasing stage of exercise. Peak modal velocity, peak
      acceleration, heart rate, and manually obtained systolic blood pressure had ICCs
      of 0.75 or greater by stage 3. The reliability of Doppler-derived aortic blood
      flow parameters was good or excellent at rest and advanced stages of exercise.
      Continuous-wave Doppler echocardiography is a reliable method for performing
      studies to assess the effects of interventions on cardiovascular function during
      exercise.

PMID- 7710748
TI  - Automated echocardiographic quantification of left ventricular volumes and
      ejection fraction: validation in the intensive care setting.
AB  - To validate automated boundary detection measurements of left ventricular
      volumes, cardiac output, and ejection fraction, we studied 50 patients in the
      intensive care unit. End-diastolic volume, end-systolic volume, and ejection
      fraction were calculated by automated boundary detection and compared with two
      dimensional echocardiographic images. Automated boundary detection-derived
      cardiac output was compared with thermodilution measurements and Doppler
      calculations of flow through the aortic and pulmonic valves. Automated boundary
      detection agreed well with two-dimensional measurements for end-diastolic volume
      (r = 0.98), end-systolic volume (r = 0.98), and ejection fraction (r = 0.91).
      Cardiac output derived from automated boundary detection correlated with two
      dimensional echocardiographic measurements (r = 0.84), thermodilution (r = 0.83),
      aortic valve Doppler (r = 0.75), and pulmonic valve Doppler (r = 0.60). Automated
      boundary detection measurements of left ventricular volumes, ejection fraction,
      and derived cardiac output are feasible in patients in intensive care units. This
      method yields rapid, accurate result compared with thermodilution, two
      dimensional images, and Doppler measurements.

PMID- 7710749
TI  - Relationship between left ventricular wall thickness and left atrial size:
      comparison with other measures of diastolic function.
AB  - We postulated that in patients with essential hypertension and normal left
      ventricular (LV) systolic function, left atrial (LA) size correlates with LV wall
      thickness by better reflecting the chronicity and duration of LA hypertension
      than the commonly used hemodynamic and Doppler measures of LV diastolic function.
      Accordingly, hemodynamic, Doppler, and two-dimensional echocardiographic
      measurements were performed in 30 subjects with no cardiovascular abnormalities
      other than essential hypertension (mean systolic blood pressure of 150 +/- 29 mm
      Hg). The mean LV wall thickness was 0.57 +/- 0.14 cm/m2 and the mean LV ejection
      fraction was 0.62 +/- 0.12. Hemodynamic and Doppler measures including pulmonary
      capillary wedge and LV end-diastolic pressures, isovolumic LV pressure
      relaxation, LV chamber elastic stiffness, and E/A ratio (E and A waves on the
      pulsed Doppler signal of the mitral valve) correlated poorly (r = 0.01 to -0.52)
      with LV wall thickness. Both E/A ratio and isovolumic LV pressure relaxation
      correlated better (p = 0.05) with patient age than with LV wall thickness. In
      contrast, LA area (in the apical four-chamber view) had a good correlation (r =
      0.77 for LA area in atrial diastole and r = 0.86 for LA area in atrial systole)
      with LV wall thickness. Multiple regression analysis revealed LA area in atrial
      systole to be the best correlate of LV wall thickness. We conclude that because
      the left atrium is a thin-walled structure, its size may increase with an
      increase in LA pressure. In the absence of mitral valve disease and atrial
      fibrillation, LA size may reflect the chronicity and duration and thus the
      history of LA hypertension. LA size in the apical four-chamber view may,
      therefore, provide a simple noninvasive assessment of the degree of LV diastolic
      dysfunction.

PMID- 7710751
TI  - Use of multiple views in the echocardiographic assessment of pulmonary artery
      systolic pressure.
AB  - The purpose of this study was to determine which echocardiographic views most
      reliably demonstrate the maximum velocity of a tricuspid regurgitant jet in the
      evaluation of pulmonary artery systolic pressure. Consecutive patients seen in
      three echocardiographic laboratories during a 3-month period were enrolled. A
      complete Doppler examination was performed on each patient, including a
      continuous-wave Doppler evaluation of tricuspid regurgitation in each of seven
      views. All seven views were used to determine the maximum velocity of tricuspid
      regurgitation. Of the 1163 studies, 866 (75%) had some tricuspid regurgitation by
      color-flow Doppler and 614 (53%) had a measurable velocity of tricuspid
      regurgitation in at least one view. No single echocardiographic view consistently
      yielded the maximum velocity of tricuspid regurgitation. The apical four-chamber
      view alone was inadequate. All seven views must be used to be certain that the
      maximum velocity of tricuspid regurgitation has been obtained.

PMID- 7710750
TI  - Quantification of mitral regurgitant volume by the color Doppler proximal
      isovelocity surface area method: a clinical study.
AB  - In vitro studies have demonstrated that regurgitant flow rate can be estimated by
      the color Doppler "proximal isovelocity surface area" (PISA) method. By applying
      the PISA method and continuity principle, we developed a formula to calculate
      mitral regurgitant volume: 2 pi r2.VN.FVI/Vo, where r = distance from the first
      jet alias to mitral leaflets, VN = aliasing velocity, FVI = flow velocity
      integral or regurgitant jet, and Vo = peak velocity through the regurgitant
      orifice. Doppler echocardiography was performed in 20 patients with mitral
      regurgitation. The mitral regurgitant volume was estimated by PISA and compared
      to cine ventriculographic grading. The results showed an increase in regurgitant
      volume by PISA compared with increasing angiographic grades of mitral
      regurgitation: 19 +/- 0.6, 18 +/- 5, 25 +/- 12, and 44 +/- 4 ml for grades 1+ to
      4+, respectively (r = 0.77). Thus a formula developed from PISA is able to
      identify patients with a severe grade of mitral regurgitation and to provide an
      alternate approach to the noninvasive quantitation of mitral regurgitation.

PMID- 7710752
TI  - Transthoracic Doppler echocardiographic measurements of pulmonary venous flow
      velocity patterns: comparison with transesophageal measurements.
AB  - Recently, we and other groups showed that analysis of transthoracic pulmonary
      venous flow velocity patterns is useful in the estimation of left ventricular
      diastolic function and left atrial pressure; however, it is unclear whether
      transthoracic tracings, in contrast to transesophageal tracings, provide reliable
      quantitation of the abnormal pulmonary venous flow characteristics in patients
      with and without cardiac disorders. This study was attempted to validate
      transthoracic pulmonary venous flow measurements by comparing them with
      transesophageal measurements in eight normal volunteers and 17 patients with a
      variety of cardiac disorders. Transesophageal and transthoracic measurements of
      peak diastolic forward flow velocity, the ratio of peak systolic/diastolic
      forward flow velocities, and the peak reversal flow velocity at atrial
      contraction sampled in the right upper pulmonary vein showed good correspondence
      to each other. The flow velocities were higher in the right upper pulmonary vein
      than in the left upper pulmonary vein. Narrower spectral flow velocity patterns
      with higher velocities were obtained 1 to 2 cm distal to the orifice in the
      pulmonary vein than at the orifice. Thus transthoracic measurements of the
      pulmonary venous flow velocity pattern are feasible and accurate in patients and
      may be used to assess left ventricular function and hemodynamics as a substitute
      for transesophageal measurements.

PMID- 7710753
TI  - Does multiplane transesophageal echocardiography improve the assessment of
      prosthetic valve regurgitation?
AB  - Assessment of prosthetic valve regurgitation by echocardiography remains
      difficult. To study the value of the newly introduced multiplane transesophageal
      technology for this purpose, prosthetic valve regurgitation was examined in 63
      consecutive patients with 35 mitral and 33 aortic prostheses (23 bioprostheses
      and 45 mechanical prostheses). Transvalvular, paravalvular and, in mechanical
      valves, normal or pathologic transvalvular regurgitation were identified first
      with 0 degrees (transverse) and 90 degrees (longitudinal) planes combined with
      flexion of the echoscope tip and then additionally with multiple intermediary
      planes by transducer rotation. In a subgroup of 20 patients interobserver
      variability was evaluated. Both methods showed regurgitation in 56 of 68 valves;
      one additional case of regurgitation was seen by multiplane imaging only.
      However, 19 cases of regurgitation were not clearly classifiable by biplane
      transesophageal echocardiography compared with only three with multiplane
      transesophageal echocardiography. Grading of severity was concordant by both
      modalities in 66 and discordant in only two cases. Observers disagreed on
      severity in two of 20 cases based on biplane imaging but in none based on
      multiplane imaging; classification of regurgitation differed in six of 20
      (biplane) and one of 20 (multiplane), respectively. Multiplane transesophageal
      imaging improves classification of prosthetic regurgitation but has little effect
      on severity grading.

PMID- 7710754
TI  - The value of transthoracic echocardiography during percutaneous balloon mitral
      valvuloplasty.
AB  - Percutaneous balloon mitral valvuloplasty is a standard alternative to surgery in
      a selected group of patients with symptomatic dominant rheumatic mitral stenosis.
      With careful transthoracic and transesophageal echocardiographic selection of
      patients, there is a low complication and high success rate. Echocardiography has
      also been established as extremely useful in the long-term follow-up of patients.
      We present four cases that highlight our view that transthoracic echocardiography
      should be performed during the procedure, after each balloon inflation, and
      before and after the intervention. In our experience transthoracic
      echocardiography during balloon mitral valvuloplasty is invaluable in assessing
      commissural separation, increasing mitral valve area, new mitral regurgitation,
      and occasional unexpected anatomic sequelae of balloon inflation.

PMID- 7710755
TI  - Congenital absence of the pericardium: echocardiography as a diagnostic tool.
AB  - Between 1982 and 1992, 10 patients who underwent echocardiography at the Mayo
      Clinic were found to have congenital absence of the pericardium. Clinical,
      electrocardiographic, chest roentgenographic, echocardiographic, computed
      tomographic, and magnetic resonance imaging features were reviewed in this
      patient group. The characteristic features of this entity are reviewed. The
      echocardiographic features in order of frequency are (1) unusual
      echocardiographic windows, seen in all 10 patients, (2) cardiac hypermobility in
      nine patients, (3) abnormal ventricular septal motion in eight patients, and (4)
      abnormal swinging motion of the heart in seven patients.

PMID- 7710756
TI  - Pharmacologically induced myocardial ischemia: a comparison of dobutamine and
      dipyridamole.
AB  - The purpose of our study was to compare the ability of dobutamine and
      dipyridamole infusion to induce myocardial ischemia. In a population of 16
      anesthetized open-chest swine, a coronary artery stenosis sufficient to abolish
      the hyperemic response to a 15-second total occlusion was created. Heart rate,
      systolic blood pressure, and dP/dt were recorded. Myocardial segment shortening
      was determined by sonomicrometry in all animals. In a subset of seven animals
      regional myocardial blood flow was measured by injection of radiolabeled
      microspheres. Dipyridamole was infused according to a high-dose protocol. After a
      washout period and reestablishment of a baseline state, dobutamine was infused
      incrementally. There was no significant difference between the baseline states.
      Dipyridamole did not affect heart rate but did significantly decrease blood
      pressure and rate-pressure product. Myocardial segment shortening decreased in
      the ischemic zone by 0.07 +/- 0.08 (p = 0.004). Dobutamine infusion significantly
      increased heart rate, blood pressure, and rate-pressure product. Myocardial
      segment shortening in the ischemic zone decreased by 0.17 +/- 0.09 (p < 0.001).
      Dobutamine decreased blood flow in the ischemic zone relative to baseline. Both
      dobutamine and dipyridamole infusion resulted in myocardial ischemia. The
      magnitude of the ischemic response is greater for dobutamine than for
      dipyridamole.

PMID- 7710757
TI  - Echocardiographic diagnosis of discontinuous left pulmonary artery as an isolated
      lesion.
AB  - The diagnosis of a discontinuous left pulmonary artery arising from a left ductus
      arteriosus was made by two-dimensional and Doppler echocardiography in an infant
      with recurrent pneumonia. The diagnosis was later confirmed at cardiac
      catheterization and surgery. The suprasternal notch views were especially useful
      for the identification of the left pulmonary artery. In this patient with a right
      aortic arch, the left pulmonary artery was supplied by a left ductus arteriosus
      that arose from the innominate artery. This case report describes the
      echocardiographic diagnosis of discontinuous left pulmonary artery as an isolated
      lesion, an unusual lesion that can easily be missed. It emphasizes the necessity
      of a careful and complete examination with particular emphasis on pulmonary
      artery continuity in patients suspected of having congenital heart disease or
      respiratory compromise as a result of a cardiovascular cause.

PMID- 7710758
TI  - Tumor invasion of the pulmonary veins: a unique source of systemic embolism
      detected by transesophageal echocardiography.
AB  - Two patients with a malignancy involving the lungs and spontaneous systemic
      embolization in whom transesophageal echocardiography detected masses consistent
      with tumor invading the pulmonary veins are reported. In the first patient, tumor
      embolization resulted in acute aortic obstruction. Transesophageal
      echocardiography revealed tumor present in the pulmonary veins that extended into
      the left atrium. This was confirmed by magnetic resonance imaging. The second
      patient had a stroke. Transesophageal echocardiography demonstrated a mass in the
      right pulmonary vein in this patient as well. In patients with pulmonary
      malignancy who have a systemic embolic event, tumor emboli from the pulmonary
      vein should be included in the differential diagnosis of possible causes of the
      event. Transesophageal echocardiography is a valuable tool for diagnosis of tumor
      involvement of the pulmonary veins in such patients.

PMID- 7710759
TI  - Expression of surrogate light chain in common variable immunodeficiency.
AB  - VpreB and lambda-like genes encode proteins that can associate to form a light
      chain-like structure, the surrogate light chain (SLC). VpreB and lambda-like
      genes are selectively expressed in human progenitor B and precursor B (pre-B)
      cells. We analyzed the expression of VpreB and lambda-like genes in seven
      patients with common variable immunodeficiency (CVI). Gene expression was
      examined in the peripheral blood mononuclear cells (PBMCs) using the polymerase
      chain reaction. In four CVI patients, two of whom were brothers, the expression
      of the VpreB gene was detectable in the PBMCs. In the brothers with CVI, the
      expression of the VpreB gene was also examined in bone marrow cells, where it was
      found to be expressed in trace amounts. A number of the brothers' bone marrow
      cells were stained with mu and kappa antibodies using the avidin-biotin complex
      method. In lambda 5-gene-deleted mice, B cell development in the bone marrow is
      blocked at the pre-B stage, but the blockade is leaky. We suggest that expression
      of the SLC is weak in patients with CVI compared with their normal counterparts,
      and this may be one of the underlying mechanisms of CVI.

PMID- 7710760
TI  - Complement and IgG subclasses in agammaglobulinemic patients.
AB  - Complement and IgG subclass analysis was performed in six agammaglobulinemic
      patients suffering from recurrent bacterial infections. Complement analysis
      included functional activity of the classical (CH50) and the alternative pathway
      (APH50) of complement, the complement proteins C3, C4, factor B, the regulators
      C1-inhibitor, factors H and I as well as the C3-derived split product C3dg/C3d.
      Plasma concentrations of total IgG ranged between < 0.01 and 297 mg/dl. IgM and
      IgA were almost undetectable. Levels of all IgG subclasses, which in most cases
      were measurable only by sensitive ELISA, were markedly reduced in all patients. A
      pronounced activation of the complement system was observed in all patients as
      revealed by reduced titers of hemolytic function and elevated levels of C3dg/C3d.
      Despite the fact that complement activation by itself was the major reason for
      decreased C4 levels, from depressed plasma concentrations of the common allotypic
      variants C4A and C4B, a heterozygous C4 deficiency could not be excluded in 2/6
      patients. Our data clearly show that, by application of sensitive analytical
      methods, agammaglobulinemic patients vary considerably in their ability to
      synthesize immunoglobulins. This may, at least in part, explain the heterogeneous
      pattern of clinical symptoms. The increased susceptibility of agammaglobulinemic
      patients to bacterial infections is reflected by a highly activated, and thereby
      depleted complement system.

PMID- 7710761
TI  - First study of immunoglobulin and T cell receptor gene rearrangements in chronic
      and acute lymphoblastic leukemias from Tunisia.
AB  - We report the first characterization at the immunological and molecular level of
      12 cases of chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia
      (ALL) from Tunisia. Our results show biallelic IgH gene rearrangement in B-CLL
      (6/6). A high ratio of T-ALL (4/6) was observed in Tunisian ALL leukemias. One T
      ALL expressed CD10 (common ALL) which has already been found in some other cases
      of T-ALL. We report the occurrence of T cell receptor (TCR) beta and/or gamma
      gene rearrangements in two precursor B-ALL patients who had normally rearranged
      Ig genes. In one precursor B-ALL case, multiple rearranged IgH and TCR gamma
      bands allowed the identification of three clones. Such an oligoclonal ALL is
      interesting since only rare biclonal TCR beta or gamma gene rearrangements have
      been described.

PMID- 7710762
TI  - Orosomucoid and haptoglobin types in patients with sarcoidosis.
AB  - Association with HLA and complement factors has been reported in sarcoidosis, and
      the results of previous studies suggest a multifactorial and immunogenetic
      etiology of the disease. We have studied two genetic acute-phase reactant
      systems, orosomucoid (ORM) and haptoglobin (HP), in 226 patients with sarcoidosis
      and population controls from northern Sweden. Significant allele and phenotype
      differences between patients and controls were found in both systems. The ORM1
      phenotype showed a significant increase in sarcoidosis (RR = 1.34, p = 0.036),
      which was more pronounced among patients with low (< 1,500 nkat/l) angiotensin
      converting enzyme levels (RR = 1.83, p = 0.00065) and hypercalcemia (RR = 3.69, p
      = 0.0023). The HP1 type was significantly increased among the sarcoidosis
      patients (RR = 1.57, p = 0.013). The results suggest that the ORM1 1 and HP1
      types may be contributory determinants in the multifactorial etiology of
      sarcoidosis.

PMID- 7710763
TI  - Biochemical analysis of HLA-DP gene products by isoelectric focusing and
      comparison with cellular and molecular genetic typing results.
AB  - The polymorphism of HLA-DPA1 and HLA-DPB1 genes of 39 lymphoblastoid cell lines,
      representing 3 DPA1 and 14 DPB1 alleles, was studied after immunoprecipitation of
      DP molecules, subsequent isoelectric focusing (1D-IEF) and immunoblotting by a
      polyclonal DP antibody. Two 1D-IEF variants for DPA1 and 7 for DPB1 gene products
      were identified, including 2 new variants associated with the DPB1*1401 and
      DPB1*1901 alleles. The 1D-IEF polymorphism correlated clearly with molecular
      genetic-defined alleles and primed lymphocyte or T cell line (PLT) specificities
      with exceptions observed in DUCAF (DPB1*0202) and ARBO (DPB1*0101). Both
      exceptional cases may reflect amino acid variations outside the hypervariable
      regions (HVRs) at the second exon of DPB1. The findings were supported by a
      comparison of HVR amino acid sequences with estimated net charges to the
      isoelectric points of the DPB1 molecules. 1D-IEF seems to be a valuable method
      for studying the expression of DPA1 and DPB1 alleles provided the molecules
      differ in their isoelectric points.

PMID- 7710764
TI  - Recombinant haplotype bearing the lymphopenia gene of the BB rat.
AB  - The development of insulin-dependent diabetes mellitus in the BB rat requires the
      presence of the class II major histocompatibility complex alleles of the RT1u
      haplotype and a T cell lymphopenia. The lymphopenia gene (lyp) behaves as an
      autosomal recessive trait that co-segregates with markers of rat chromosome 4.
      The current study examines two congenic and four recombinant inbred rat strains
      derived from BB and Buffalo rat strains using markers for simple-sequence length
      polymorphisms to confirm the linkage of the lymphopenia gene to chromosome 4. In
      two of these lines the lymphopenia associates with a recombinant haplotype that
      is BB-like at the D4Mit6 marker and Buffalo-like at D4Mit7 (neuropeptide Y locus)
      thus placing the lyp locus between these two closely linked markers.

PMID- 7710765
TI  - Expression of the complement C8 genes during interleukin-6-mediated in vitro
      induction of the acute-phase response.
AB  - The three chains of the human complement component C8-alpha, beta and gamma- are
      encoded by distinct structural genes. C8A and C8B are closely linked on
      chromosome 1p and C8G is located on chromosome 9q. The biosynthesis and
      regulation of the gene products were studied in the human hepatoma-derived cell
      line HepG2 after in vitro induction of the acute-phase response by incubation
      with the cytokine interleukin IL-6. Analysis of C8 expression by
      immunoprecipitation and SDS-PAGE of biosynthetically labeled alpha-gamma and beta
      subunits demonstrated a positive response to this cytokine. The expression
      pattern observed in the hepatoma cells characterizes C8 in vitro as a positive
      acute-phase protein. In addition, the comparison of the relative amounts of the
      C8 transcripts provides evidence for a post transcriptional regulation of the C8
      beta subunit. No evidence was obtained for an increased expression of IL-6 or IL
      6 receptor mRNA thus excluding autoregulatory mechanisms of the cytokine in HepG2
      cells.

PMID- 7710766
TI  - ATP-dependent transport of glutathione-N-ethylmaleimide conjugate across
      erythrocyte membrane.
AB  - Prevailing controversies regarding the identity and nature of S-(2,4
      dinitrophenyl) glutathione (Dnp-SG) and GSSG transport system(s) led us to
      examine xenobiotic-SG transport from human erythrocytes and into inside-out
      vesicles (IOV) using N-ethyl-maleimide-glutathione conjugate (NEM-SG) as
      substrate. Efflux of NEM-SG from intact erythrocytes was linear over a period of
      4 h, occurred against a concentration gradient, and required energy. No transport
      of NEM-SG was observed when endogenous ATP was exhausted by preincubation of the
      erythrocytes for 8 h at 37 degrees C in the absence of glucose. When cellular GSH
      was partially conjugated with NEM to form 1.5 and 1.0 mM NEM-SG, and the
      remaining GSH was oxidized with t-butylhydroperoxide to generate 0.2 and 0.4 mM
      GSSG, respectively, the extrusion of NEM-SG from erythrocytes was not inhibited.
      The kinetics of NEM-SG transport in intact erythrocytes were monophasic; the Km
      NEM-SG was 0.62 mM +/- 0.24. However, in IOV two components of NEM-SG transport
      with respect to NEM-SG and ATP were discernible. The low Km for NEM-SG was 5.6 +/
      1.51 microns with a Vmax of 7.30 +/- 0.69 nmol/mg protein/h and the high Km for
      NEM-SG was 1.35 +/- 0.14 mM with a Vmax of 65.1 +/- 3.5 nmol/mg protein h. With
      respect to ATP, the NEM-SG transport had a low Km of 0.12 +/- 0.004 mM and a high
      Km of 0.52 +/- 0.052 mM. Both components of NEM-SG transport were inhibited by
      fluoride, o-vanadate, p-hydroxymercuribenzoate and 5,5'-dithiobis(2-nitrobenzoic
      acid). However, NEM (1 mM) inhibited only the high Km transport. GSH stimulated
      the low Km transport 1.7-fold. Both low and high Km components of NEM-SG
      transport significantly declined when ATP was substituted with CTP, UTP, or GTP.
      GSSG and Dnp-SG competitively inhibited the low Km NEM-SG transport (Ki = 18.5 +/
      2.9 and 1.32 +/- 0.16 microns, respectively) whereas the high Km transport was
      inhibited by Dnp-SG but not by GSSG. These findings suggest that glutathione S
      conjugates may be transported out of erythrocytes by both the high and the low Km
      mechanisms, the latter being shared by GSSG.

PMID- 7710767
TI  - Enzymatic and secretory activities in pancreatic islets of non-insulin-dependent
      diabetic rats after short-term infusion of succinic acid monomethyl ester.
AB  - The monomethyl ester of succinic acid (SME) was recently proposed as a novel tool
      for stimulation of proinsulin biosynthesis and insulin release in animal models
      of non-insulin-dependent diabetes mellitus. In the present study, either saline
      or SME (14 mmol/day) was infused for 3 days to control rats, animals injected
      with streptozotocin during the neonatal period, and Goto-Kakizaki rats with
      inherited diabetes. The infusion of SME failed to correct the anomalies found in
      the islets of diabetic rats, namely, a decreased activity of the mitochondrial
      FAD-linked glycerophosphate dehydrogenase, a low insulin content, and an impaired
      secretory response to various nutrient secretagogues including D-glucose, 2
      ketoisocaproate, and the combination of L-leucine and L-glutamine. These findings
      raise the question of whether a more prolonged administration of SME is required
      to raise the insulin store and improve the secretory potential of the endocrine
      pancreas in animals with type 2 diabetes.

PMID- 7710768
TI  - Rabbit optic nerve phosphorylates glucose through a glucokinase-like enzyme:
      studies in normal and spontaneously hyperglycemic animals.
AB  - We investigated glucose phosphorylation at various concentrations of glucose (1,
      5, 10, 25, 50, 100 mmol/liter) in rabbit optic nerve. In the 3000 g supernatant
      of whole rabbit optic nerve homogenates from female albino rabbits (n = 10, 1.8
      2.0 kg body weight, mean +/- SEM morning glycemia: 8.25 +/- 0.29 mmol/liter), the
      glucose phosphorylating activity (NADP reduction measured as change in optical
      density at 366 nm at pH 7.5) increased progressively with the increase in glucose
      concentration (r = 0.89; P < 0.05) and approached the maximum at a very high
      glucose level (100 mmol/liter), with values (mean +/- SEM) of 8.75 +/- 0.97
      nanomol/min/mg protein and 11.57 +/- 1.15 at 1 and 100 mmol/liter glucose,
      respectively (+32.23%; P < 0.01). At a more alkaline pH (8.2; n = 5, mean +/- SEM
      morning glycemia: 8.83 +/- 0.07 mmol/liter) glucose phosphorylation was higher
      than at pH 7.5 and retained the glucose concentration dependence (r = 0.95, P <
      0.01). These kinetic characteristics are reminiscent of those of the low-affinity
      enzyme glucokinase, which is typically present in the liver. By subtracting the
      activity at 1 mmol/liter glucose from that at higher glucose concentrations, we
      calculated the "glucokinase component," forms the "total" glucose phosphorylating
      activity. In five rabbits (of similar age and weight) with spontaneous
      hyperglycemia (mean +/- SEM: 11.71 +/- 0.60 mmol/liter), the optic nerve glucose
      phosphorylating activity was lower (value at 1 mmol/liter glucose: 5.42 +/- 1.31,
      -38.06%, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7710769
TI  - Stimulation of interleukin-6 production of periodontal ligament cells by
      Porphyromonas endodontalis lipopolysaccharide.
AB  - Interleukin-6 (IL-6), which is a multifunctional cytokine, has important roles in
      acute and chronic inflammation and may also be implicated in bone resorption. We
      examined the IL-6 production in periodontal ligament (PDL) cells which were
      treated with lipopolysaccharide (LPS) from several oral inflammatory pathogens.
      The LPS from Porphyromonas endodontalis, which was isolated from infected root
      canals and radicular cyst fluids, was more potent than the LPS from any other
      periodontal organisms examined. P. endodontalis LPS stimulated IL-6 release from
      PDL cells in a time- and dose-dependent manner. Northern blot hybridization
      analysis revealed that the IL-6 mRNA level in PDL cells was increased by P.
      endodontalis LPS. These results suggest that stimulation of the IL-6 release of
      PDL cells by P. endodontalis LPS may have a role in the progression of
      inflammation and alveolar bone resorption in periodontal and periapical diseases.

PMID- 7710770
TI  - Effects of long-term streptozotocin diabetes on cytoskeletal and cytosolic
      phosphofructokinase and the levels of glucose 1,6-bisphosphate and fructose 2,6
      bisphosphate in different rat muscles.
AB  - We show here that long-term streptozotocin diabetes affects differently the
      intracellular distribution of phosphofructokinase (PFK), the rate-limiting enzyme
      of glycolysis, in tibialis anterior and gastrocnemius muscles. Diabetes, which
      causes ultrastructural damage in both muscle fibers, induced a decrease in PFK
      binding to cytoskeleton in gastrocnemius muscle but not in the tibialis anterior
      muscle. However, the allosteric activity of cytoskeleton-bound and soluble PFK
      was reduced in both kinds of muscles, most probably due to the decrease in the
      level of glucose 1,6-bisphosphate, the potent allosteric activator of the enzyme.
      Levels of fructose 2,6-bisphosphate remained unchanged. A change in the
      allosteric properties of the cytoskeleton-bound PFK was found only in the
      diabetic tibialis anterior muscle; in contrast to normal muscle, where only the
      soluble but not the bound enzyme responded to allosteric effectors, in the
      diabetic tibialis anterior muscle, the bound enzyme exhibited allosteric
      properties similar to the soluble enzyme. The reduction in both cytosolic and
      cytoskeletal PFK, and, thereby, glycolysis in these two kinds of muscles, which
      results most probably from the reported high pathological intracellular Ca2+
      concentration, may contribute to muscle damage in diabetes.

PMID- 7710771
TI  - Hexokinase binding in ischemic and reperfused piglet brain.
AB  - Hexokinase catalyzes the first step in cerebral glucose utilization and is a rate
      limiting enzyme in glycolysis. Glucose utilization is tightly coupled to cerebral
      blood flow so that during ischemia the brain has a decreased supply of glucose,
      as well as oxygen. We studied hexokinase enzymatic activity in a newborn piglet
      model of ischemia-reperfusion to determine if any changes in the activity or
      mitochondrial binding of the enzyme occurred. We observed that mitochondrial
      binding of cortical HK increased from 55 to 71% with ischemia and returned toward
      control levels, but did not completely recover, after 2 h of reperfusion.

PMID- 7710772
TI  - Rapid antenatal diagnosis of beta-thalassemia in Chinese caused by the common 4
      bp deletion in codons 41/42 using high-resolution agarose gel electrophoresis and
      heteroduplex detection.
AB  - The 4-bp deletion in codons 41/42 (-TTCT) in the beta-globin gene is a common
      mutation that causes beta-thalassemia in Chinese. A simple method, which involved
      PCR amplification of the relevant region, was used for the antenatal diagnosis of
      a fetus at risk for this mutation. The fetal PCR product showed a single fragment
      of normal size on MetaPhor gel. The homozygous normal status was further
      confirmed by the generation of heteroduplexes only after addition of homozygous
      mutant DNA.

PMID- 7710774
TI  - Characteristics of proteinuria in experimental diabetes mellitus.
AB  - An impairment of protein charge selectivity has been invoked to explain the
      initial anionic proteinuria in diabetic nephropathy. The aims of this work were
      to investigate charge and size protein perm-selectivity abnormalities in
      experimental diabetes and to monitor these changes over time after diabetes
      induction. Diabetes was induced in 56 Sprague-Dawley male rats by streptozotocin;
      the control group was represented by 38 normal rats. Blood glucose, body weight,
      urine volumes, and proteinuria in 24-h urine collections were evaluated at 3, 6,
      9, and 12 months of diabetes. The Bradford method and mono- and bidimensional gel
      electrophoresis were used to determine and characterize proteinuria. Body weight
      increase was lower (P < 0.05, P < 0.0001, P < 0.05 at 3, 6, and 12 months,
      respectively), urine volumes were greater (P < 0.001, P < 0.005, P < 0.05 at 6,
      9, and 12 months, respectively) and the proteinuria was significantly increased
      (P < 0.05 at 3 months, P < 0.001 at 6 months, P < 0.01 at 9 months, and P < 0.05
      at 12 months) in diabetic rats compared with the control group. When the charge
      and the size of urine proteins were considered, small (30 kDa) and anionic
      proteins were found to be mainly excreted in diabetic rats, at 3 months of the
      disease; at 6 months, higher amounts of albumin and cationic proteins with higher
      molecular weight (50 kDa) were also found in the urine; at 9 and 12 months the
      changes previously described were associated with an excretion of proteins
      weighing about 75 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7710773
TI  - Glutathione metabolism in Crohn's disease.
AB  - A statistically significant decrease of glutathione (GSH) and an increase of GSH
      disulfide (GSSG) both in healthy and ill ileum of patients with Crohn's disease
      in comparison with the controls (without this pathology) is demonstrated.
      However, the lowering of these levels was more remarkable in ill ileum in which
      high levels of GSSG were detected, too. These alterations may be in part
      explained by the changes obtained in GSH-related enzyme levels. Finally,
      considering the results that others and we obtained by studies on GSH oral
      absorption in rat intestine, an oral therapy of GSH in Crohn's disease is
      suggested.

PMID- 7710775
TI  - Time dependence of plasma malondialdehyde, oxypurines, and nucleosides during
      incomplete cerebral ischemia in the rat.
AB  - Incomplete cerebral ischemia (30 min) was induced in the rat by bilaterally
      clamping the common carotid arteries. Peripheral venous blood samples were
      withdrawn from the femoral vein four times (once every 5 min) before ischemia (0
      time) and 5, 15, and 30 min after ischemia. Plasma extracts were analyzed by a
      highly sensitive high-performance liquid chromatographic method for the direct
      determination of malondialdehyde, oxypurines, and nucleosides. During ischemia, a
      time-dependent increase of plasma oxypurines and nucleosides was observed. Plasma
      malondialdehyde, which was present in minimal amount at zero time (0.058
      mumol/liter plasma; SD 0.015), increased after 5 min of ischemia, resulting in a
      fivefold increase after 30 min of carotid occlusion (0.298 mumol/liter plasma; SD
      0.078). Increased plasma malondialdehyde was also recorded in two other groups of
      animals subjected to the same experimental model, one receiving 20 mg/kg b.w. of
      the cyclooxygenase inhibitor acetylsalicylate intravenously immediately before
      ischemia, the other receiving 650 micrograms/kg b.w. of the hypotensive drug
      nitroprusside at a flow rate of 103 microliters/min intravenously during
      ischemia, although in this latter group malondialdehyde was significantly higher.
      The present data indicate that the determination of malondialdehyde, oxypurines,
      and nucleosides in peripheral blood, may be used to monitor the metabolic
      alterations of tissues occurring during ischemic phenomena.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7710777
TI  - Special issue on P1 cloning.

PMID- 7710776
TI  - Direct sequencing of terminal regions of genomic P1 clones. A general strategy
      for the design of sequence-tagged site markers.
AB  - A method for the preparation of P1 DNA is presented, which allows the direct
      sequencing of ends of inserts in genomic P1 clones using the Applied Biosystems
      373A DNA Sequencer and the Dye Terminator sequencing methodology. We surveyed
      several common methods of DNA preparation including alkaline lysis, Triton
      lysozyme lysis, CsCl density-gradient purification, and a commercial column
      matrix DNA purification kit manufactured by Qiagen. We found that a modified
      alkaline lysis preparation of P1 DNA was most successful for generating P1 DNA
      that could be sequenced directly. We also noted that the host bacterial strain
      from which the P1 DNA was purified dramatically affected the quality of
      sequencing templates. The bacterial strains NS3145 and NS3529, in which the
      Drosophila melanogaster and human P1 genomic libraries are harbored, routinely
      yielded poor-quality sequencing templates. However, the bacterial strain DH10B
      routinely yielded P1 DNA that was sequenced successfully. A bacterial mating
      scheme is presented that exploits gamma delta transposition events to allow the
      transfer of P1 clones from the library host strain to DH10B. Using either an SP6
      or a T7 primer, an average of 350 base pairs of DNA sequence was obtained with an
      uncalled base frequency of approximately 2%. About 4% of P1 end sequences
      generated corresponded to unique Drosophila loci present in the Genbank database.
      These single-pass DNA sequences were used to design sequence-tagged site markers
      for physical mapping studies in both humans and Drosophila.

PMID- 7710778
TI  - Isolation of P1 bacteriophage clones containing large contiguous segments of the
      human and mouse loci for the T-cell coreceptor molecule CD8.
AB  - The T-lymphocyte coreceptor molecules CD8 (composed of CD8 alpha and CD8 beta
      chains) and CD4 undergo a complex pattern of regulated expression during T-cell
      maturation. In the thymus, the most immature cells progress from expressing
      neither molecule (the double-negative [DN] stage) to an intermediate stage at
      which both are coexpressed (the double-positive [DP] stage). As a result of
      thymic selection and further differentiation, DP cells give rise to the most
      mature thymic cells and peripheral T cells that express either CD8 or CD4 (the
      single-positive [SP] stage). Our previous studies of the transcriptional
      regulatory mechanisms controlling CD8 alpha expression during the DN-->DP and DP-
      >SP transitions suggest the existence of important cis-acting elements located a
      considerable distance from the CD8 alpha gene and that these elements might serve
      to regulate both CD8 alpha and CD8 beta. While both genes and intergenic DNA span
      approximately 60 kb in the mouse, the relevant cis elements could lie either
      within or beyond this region. As a result, we sought to isolate large contiguous
      segments of DNA in P1 bacteriophage that covered at least this region from the
      mouse and human CD8 locus. Our initial physical characterization of these clones
      demonstrates the value of the P1 system as all isolated clones were found to
      contain single contiguous 85- to 95-kb segments of DNA that are faithful replicas
      of the chromosomal locus. The presence of abundant native flanking DNA both
      upstream and downstream of the intact coding regions will make these clones
      extremely useful for identifying physiological CD8 cis-active regulatory elements
      by virtue of their ability to direct appropriate lineage- and stage-specific
      expression in transfected and transgenic T cells.

PMID- 7710779
TI  - Large-scale isolation of human 1p36-specific P1 clones and their use for
      fluorescence in situ hybridization.
AB  - A series of 80 microclone probes derived from the chromosomal region 1p36 was
      used to isolate corresponding clones from the ICRF human P1 library (see Francis
      et al., this issue). Hybridization screenings were performed using probe pools on
      high-density filter grids. A total of 87 P1 clones specific for 1p36 were
      isolated. This large-scale approach allowed a detailed evaluation of the
      complexity, quality, and utility of this library. The isolated P1 clones were
      used both for size determination by pulsed-field gel electrophoresis and as
      probes for fluorescence in situ hybridization (FISH) analysis. FISH of P1 clones
      is shown to be both easy and efficient to perform on metaphase chromosomes and
      interphase nuclei. This observation is expected to reveal new avenues for
      diagnosis of disease-related chromosomal changes. The use of P1 clones as a tool
      in clinical and tumor interphase cytogenetics is discussed and compared with FISH
      data of other long insert clones such as cosmids and YAC clones.

PMID- 7710780
TI  - Construction and preliminary analysis of the ICRF human P1 library.
AB  - P1 clone libraries have now been established as effective complements to cosmid
      and yeast artificial chromosome libraries in long-range mapping projects. To
      allow general access to P1 clones, we have constructed human and mouse P1
      libraries. Clones have been picked into microtiter plates and used to prepare
      high-density filter grids, providing an efficient and easy screening system.
      Filters are being made available to other laboratories through the Reference
      Library System. In this work, we have developed a reliable protocol for
      generating P1 clones, based on the use of pulsed-field gel electrophoresis for
      size selection of DNA. A 1.2x genome coverage human library has been produced
      using this method. A preliminary analysis of this library is described.

PMID- 7710781
TI  - Expression of P1 DNA in mammalian cells and transgenic mice.
AB  - Because the P1 bacteriophage packages DNA inserts of 80-100 kb, which are much
      larger than inserts of bacteriophage lambda or cosmid vectors, P1 DNA can be used
      to express large genes in cultured cells and transgenic mice. We obtained a P1
      bacteriophage clone with a 79.5-kb insert (p158) that spanned the entire human
      apolipoprotein (apo-) B gene. We used the insert from p158 to express the human
      apo-B gene in both cultured rat hepatoma cells and transgenic mice. In this
      article, we review our apo-B expression studies and discuss the techniques that
      we have used for these expression studies.

PMID- 7710782
TI  - A single P1 clone bearing three genes from human chromosome 11p15.5: HRC1, HRAS1,
      and RNH.
AB  - Molecular genetic alterations of chromosome 11p15.5 are a common finding in human
      cancer. We previously reported the characterization of two cosmids representing a
      55-kilobase (kb) region of DNA surrounding the protooncogene HRAS1. A cluster of
      genes was identified adjacent to this locus, and one of these genes, HRC1, was
      divergently transcribed 30 kb upstream from HRAS1. A recent report placed the
      gene for placental ribonuclease inhibitor (RNH, ribonuclease-angiogenin
      inhibitor) within 90 kb of HRAS1 by pulsed-field gel electrophoresis (PFGE)
      mapping. We used recombinant P1 bacteriophage clones for physical mapping to
      determine the position of RNH relative to the HRAS1 transcription unit and HRC1
      on chromosome 11p15.5. PFGE and Southern analysis of genomic DNA suggested the
      order of the genes (HRC1-HRAS1-RNH). P1 clones confirmed this assignment, and
      placed RNH within 30-50 kb of the 3' end of HRAS1. Furthermore, a single 80-kb P1
      clone that bears all three genes was isolated and clarified the Not I restriction
      map for the HRAS1-RNH interval. Their close physical association was predicted by
      simple screening of an arrayed P1 library; the clone containing all three genes
      was selected from multiple positive signals obtained for each HRC1 and RNH
      because it mapped to the same library-well address.

PMID- 7710783
TI  - Three new developments in P1 cloning. Increased cloning efficiency, improved
      clone recovery, and a new P1 mouse library.
AB  - In this report, we describe three new P1 cloning developments. Two of these
      developments represent improvements in cloning efficiency and clone recovery, and
      the third is the production and partial characterization of a new P1 mouse
      library. To increase cloning efficiency, we have produced a new lysis-defective
      (delta lydAB) P1 lysogen (NS3690) for the production of the stage II head-tail-P1
      packaging extract that is easier to use than the original stage II lysogen
      (NS3210), and that produces stage II extracts that are five- to eightfold more
      efficient than the original extracts. We believe the increased efficiency is due
      to the more concentrated packaging components in the NS3690 extract. Regarding P1
      clone recovery, we demonstrate here that the less than optimal recovery of P1
      plasmid DNA from P1 clones is due to the continuous presence of the P1 Cre
      recombinase in the host strain containing those clones (NS3529). Consequently, a
      simple method of P1 plasmid clone transduction is described to transfer clone DNA
      from NS3529 (Cre+) to its Cre- parent (NS3516). Yields of P1 plasmid DNA from
      NS3516 are as much as tenfold higher than from NS3529. Finally, we document here
      the production of a new P1 mouse library that was generated using genomic DNA
      from embryonic stem cell line E14 (a 129/0la mouse). The library contains 182,000
      independent clones whose average insert size is 80 kb and, based on > 100
      polymerase chain reaction screens, has an average unique sequence-hit size of
      4.6.

PMID- 7710785
TI  - Genetic analysis: techniques and applications bibliography.

PMID- 7710784
TI  - The complete nucleotide sequences of the SacBII Kan domain of the P1 pAD10-SacBII
      cloning vector and three cosmid cloning vectors: pTCF, svPHEP, and LAWRIST16.
AB  - The complete nucleotide sequence of the 16,009-bp SacBII Kan domain of the P1
      pAD10-SacBII cloning vector and the sequences of three cosmid cloning vectors,
      pTCF (7941 bp), svPHEP (9201 bp), and LAWRIST16 (5194 bp) have been determined. A
      modified diatomaceous earth (Prep-A-Gene)-based procedure, which rapidly yields
      highly supercoiled double-stranded DNA from recombinant P1 and cosmid clones
      suitable for generating shotgun libraries, also has been developed. The isolated
      recombinant DNAs were physically sheared to generate 1- to 2-kb fragments that
      then were blunt-ended and subcloned into double-stranded pUC-based sequencing
      vectors. The double-stranded sequencing templates were isolated by an alkaline
      lysis method and subjected to Taq polymerase catalyzed fluorescent end-labeled
      primer cycle sequencing. After shotgun sequence assembly, contig gaps were closed
      and ambiguities were resolved via Sequenase catalyzed fluorescent dye-terminator
      sequencing.

PMID- 7710786
TI  - XII International Conference on Calcium Regulating Hormones. Melbourne,
      Australia, February 14-19, 1995. Program and abstracts.

PMID- 7710787
TI  - Contrast-enhanced MR imaging of the breast in patients with breast implants after
      cancer surgery.
AB  - The purpose of the study was to determine the value of contrast-enhanced MR
      imaging in the assessment of local recurrence in breast cancer patients who
      underwent mastectomy and breast reconstruction with an implant. Eighty-three
      patients have been evaluated by semidynamic contrast-enhanced MR imaging. The T1
      weighted FLASH 3-D sequence was repeated twice postcontrast for evaluation of the
      entire breast bilaterally. The findings were compared to physical examination,
      mammography and histopathology. Recurrence verified by histopathology occurred in
      14 of 83 patients (17%). Contrast-enhanced MR imaging was superior to palpation
      and mammography in revealing recurrences, especially when these were located
      close to the chest wall. MR was also more sensitive in detecting multiple foci of
      cancers. Our study revealed that MR imaging was influenced by size, type and
      composition of the tumor, as illustrated by the false-negative results.
      Therefore, the use of all 3 investigation methods is necessary for detecting
      recurrence at an early stage during the postoperative follow-up.

PMID- 7710788
TI  - Nonpalpable breast lesion. Stereotaxic core needle aspiration biopsy with a
      single pass.
AB  - One hundred and fifty-six patients with suspect nonpalpable breast lesion
      underwent stereotaxic core needle aspiration biopsy (SCNAB) with a single pass in
      an upright "add-on" stereotaxic device using a manual 1.6-mm needle (16 G), to
      determine whether the results were comparable to results of SCNAB with a multiple
      pass technique. Of the 69 carcinomas, 51 (74%) were correctly diagnosed and
      definitive surgical therapy, without surgical biopsy, was performed in 42 of the
      50 invasive carcinomas (84%) and in 9 of the 19 noninvasive carcinomas (47%). Ten
      noninvasive carcinomas and 4 invasive carcinomas, discovered by
      microcalcifications or distortion on the mammograms, form 78% of the false
      negative results. There were no false-positive results. Vasovagal reactions
      occurred in 11% of the procedures. Although the results were acceptable in
      patients with invasive carcinoma, more than one needle pass is necessary for
      greater diagnostic accuracy of SCNAB, especially in patients with only
      microcalcifications or distortion on the mammogram.

PMID- 7710789
TI  - Pleuro-pulmonary aspergillosis. US and US-guided biopsy as an aid to diagnosis.
AB  - We reviewed the US findings and the diagnostic yield of fine-needle aspiration
      biopsy (FNAB) for cytologic and microbiologic samples in 4 patients with
      pulmonary or pleural aspergillosis. All 3 apical Aspergillus abscesses were
      round, hypoechoic with irregular margins and one contained echo-densities with
      shadowing consistent with air. One pleural empyema was oval and hypoechoic.
      Cytology suggested inflammation in all cases and Aspergillus hyphae were detected
      in 2 of 4 aspirates. Culture of the aspirate was positive for Aspergillus in 3 of
      4 cases, while one diagnosis was made after surgery. No complications occurred.
      Apico-pleural Aspergillus lesions are suitable targets for US-guided FNAB, thus
      avoiding more invasive methods. Our results suggest wider use of this procedure.

PMID- 7710790
TI  - Texture analysis in quantitative MR imaging. Tissue characterisation of normal
      brain and intracranial tumours at 1.5 T.
AB  - The diagnostic potential of texture analysis in quantitative tissue
      characterisation by MR imaging at 1.5 T was evaluated in the brain of 6 healthy
      volunteers and in 88 patients with intracranial tumours. Texture images were
      computed from calculated T1 and T2 parameter images by applying groups of common
      first-order and second-order grey level statistics. Tissue differentiation in the
      images was estimated by the presence or absence of significant differences
      between tissue types. A fine discrimination was obtained between white matter,
      cortical grey matter, and cerebrospinal fluid in the normal brain, and white
      matter was readily separated from the tumour lesions. Moreover, separation of
      solid tumour tissue and peritumoural oedema was suggested for some tumour types.
      Mutual comparison of all tumour types revealed extensive differences, and even
      specific tumour differentiation turned out to be successful in some cases of
      clinical importance. However, no discrimination between benign and malignant
      tumour growth was possible. Much texture information seems to be contained in MR
      images, which may prove useful for classification and image segmentation.

PMID- 7710791
TI  - Vascular mass lesions and hypervascular tumors in the head and neck.
      Characteristics at CT, MR imaging and angiography.
AB  - A retrospective analysis of the findings at contrast-enhanced CT, MR imaging and
      angiography in 24 patients with vascular mass lesions and 11 patients with
      hypervascular tumors in the head and neck region was undertaken. We attempted to
      find criteria at CT and MR imaging that could aid in differentiating between
      different lesion categories. Parameters such as contrast enhancement at CT,
      signal intensities at MR imaging, phleboliths and peritumoral hypervascularity
      were correlated to clinical presentation, biopsies and angiography. MR imaging
      was superior to CT and far better than angiography in delineating cavernous
      hemangiomas. Contrast-enhanced CT may better differentiate between cavernous and
      capillary hemangiomas than MR. MR imaging clearly differentiated cavernous
      hemangiomas from hypervascular tumors, but was, like CT, inadequate for
      distinguishing between capillary hemangiomas and hypervascular tumors.
      Lymphangiomas and cavernous hemangiomas had similar appearances at CT and MR
      imaging.

PMID- 7710792
TI  - Craniopharyngioma identification by CT and MR imaging at 1.5 T.
AB  - To compare the detectability of craniopharyngiomas by CT and MR imaging,
      preoperative CT and MR studies obtained within 16 days of each other were
      evaluated retrospectively in 9 patients. MR imaging demonstrated cystic and solid
      tumor components in all 9 tumors, and enhancement in the 7 tumors that were
      studied after contrast medium injection. MR imaging demonstrated a signal void
      consistent with calcification in 4 patients. Combining unenhanced and contrast
      medium-enhanced studies, CT also identified all the tumors. CT demonstrated cysts
      in 7 lesions, calcification in 7 and enhancement in 6 of the 7 lesions that
      received i.v. contrast medium. Calcification was better seen by CT than MR
      imaging, while MR imaging identified cystic tumor components not seen on CT. The
      contrast medium enhancement pattern was the same with the 2 modalities. MR
      imaging of the sellar region, including at least one contrast medium-enhanced
      sequence, should be sufficient in most instances to establish a preoperative
      diagnosis of craniopharyngioma.

PMID- 7710793
TI  - Wooden foreign bodies in CT. Case reports and experimental studies.
AB  - CT findings in 2 patients with a wooden foreign body in the orbital region soft
      tissue, and a series of CT measurements of wooden elements are presented. The
      wooden foreign bodies presented low HU numbers in CT and were initially
      interpreted as a gas collection. Different species of trees presented a large
      spectrum of densities, varying from the -550 HU of pine up to the +289 HU of
      ebony. The density of a spruce plank increased along with water-logging from -470
      HU to -86 HU in 4 weeks, and peak enhancement up to 106 HU was found in the layer
      closest to the surface. It was concluded that a wooden foreign body in soft
      tissues may present CT patterns simulating materials as different as a gas bubble
      or a bone fragment.

PMID- 7710794
TI  - Bipartite atlas and hypertrophy of its anterior arch. A case report.
AB  - On the lateral cervical spine radiographs of a 60-year-old woman complaining of
      neck pain, diffuse hyperostosis or calcification was present anterior to the
      anterior arch of the atlas. CT of atlas revealed it to be bipartite and the
      hyperostosis to be due to hypertrophy of its anterior arch. We report this as a
      new sign associated with a bipartite atlas.

PMID- 7710795
TI  - Prediction of the time to peak hepatic enhancement to optimize contrast-enhanced
      spiral CT.
AB  - A technique for the prediction of the time to peak hepatic enhancement to
      optimize contrast-enhanced spiral CT has been developed. The procedures are (a)
      to inject a small amount of contrast medium rapidly via the antecubital vein and
      measure aortic transit time (ATT) of the bolus by single slice dynamic CT; (b) to
      inject contrast medium at a high rate, expecting peak hepatic enhancement to
      occur at ATT plus 8 seconds after the end of injection; (c) to perform spiral
      scanning of the liver using thin collimation and caudo-cranial table movement
      beginning at ATT after the end of contrast medium injection.

PMID- 7710796
TI  - Percutaneous gastrostomy guided by ultrasound and fluoroscopy.
AB  - Percutaneous gastrostomy, utilizing a dedicated catheterization kit, with a
      combination of ultrasonographic (US) and fluoroscopic guidance, was carried out
      in 27 patients. The main indication for gastrostomy was the need for nutritional
      support in malignant esophageal stricture. After distending the stomach with
      water via a nasogastric tube, the gastric antrum was punctured under US guidance
      and a guide wire was inserted, followed by fluoroscopically guided tract
      dilatation and insertion of a 2.5-mm Cope-loop catheter. In all patients but one
      (96%) the procedure was successfully completed in one or 2 attempts. Two
      complications occurred: one case of a small subcutaneous abscess near the
      puncture site, and one late incident of dislodgement of a catheter without string
      loop fixation, which had been inserted at a catheter exchange after 6 weeks.
      Percutaneous gastrostomy guided by US and fluoroscopy is a safe and efficacious
      alternative to endoscopic and surgical gastrostomy.

PMID- 7710797
TI  - MR imaging of hepatocellular carcinoma. Correlation of metal content and signal
      intensity.
AB  - In order to clarify the factors contributing to the signal intensities (SIs) of
      HCC on T1-weighted images, the amount of water, lipid, copper (Cu), iron (Fe),
      and manganese (Mn) was determined in HCC and surrounding hepatic parenchyma of 13
      patients. The relationships among these findings, the histopathologic findings,
      and the SIs of T1-weighted images were evaluated. Among the 13 HCC, 3 had a high
      SI, 5 were isointense, and 5 had a low SI on T1-weighted images compared to the
      surrounding hepatic parenchyma. The paramagnetic ions which contributed to the SI
      patterns were assumed to be Cu in HCC (38.0 +/- 62.4 micrograms/g ww), and Fe in
      the liver (61.1 +/- 42.4 micrograms/g ww) and HCC (40.0 +/- 34.3 micrograms/g
      ww). In 8 HCC with high- or isointensity, 2 were grades I, 5 were grade II, and
      one was grade III according to the Edmondson-Steiner's histopathologic
      classification. It is concluded that the SI patterns alone can not be a sign of
      low grade malignancy because of the existence of Fe in livers and HCC.

PMID- 7710798
TI  - Fine needle aspiration biopsy of hydatid cysts.
AB  - Fine needle aspiration biopsy (FNAB) was performed in 31 patients with hydatid
      disease by 15 operators in 41 biopsy events during the period 1983-93. The FNABs
      were unintentionally done without prior clinical suspicion of hydatid cysts (HCs)
      in 18 patients and intentionally (with prior clinical suspicion of HC) in 13
      patients for pathologic confirmation required for specific therapy. The FNABs
      were performed with the guidance of fluoroscopy (n = 7), CT (n = 14) or
      ultrasonography (n = 10). The material included both closed, open and ruptured
      HCs from different locations such as abdomen, thorax, spine and bone. Pathologic
      confirmation of HC was achieved by recovering and demonstrating parasitic
      material in the specimen. In only 7 of 31 patients were the specimens diagnostic
      at the initial interpretation. This emphasizes the importance of alerting the
      pathologist about the possibility of hydatid disease. In 25 of 31 patients (81%)
      no biopsy reactions occurred. In 5 patients minor allergic reactions occurred and
      3 had filling of air into intrathoracic cysts not requiring therapy. One patient,
      with a FNAB of a liver HC, had a sudden severe drop in blood pressure, which
      required anti-shock therapy with subsequent recovery without sequelae. All
      complications occurred with non-intentional biopsy of HC. Suggestions for
      diagnostic and therapeutic management of patients with HC and advice to avoid or
      limit potential complications or spread of disease are given where a planned
      biopsy is necessary for appropriate and effective therapy.

PMID- 7710799
TI  - Ultrasonographic findings after conservative treatment of acute appendicitis and
      open appendicectomy.
AB  - In a randomized study we investigated the effects of antibiotics as the only
      treatment in acute appendicitis. Forty patients were examined, 19 after
      antibiotic treatment (one operated due to perforation) and 21 after surgery. All
      patients were examined prior to randomization, after 10 days and after 30 days.
      Of the positive ultrasonographic (US) findings, 18 (86%) of the 21 operated
      patients had histologically proven acute appendicitis. At the 10th day, 9
      patients had a seroma under the scar, which had disappeared a month after surgery
      in all patients. In the 19 patients conservatively treated with antibiotics, the
      appendix could be visualized in 8 symptom-free cases on the 10th day. In 5 of the
      8 patients the appendix was still visualized after 1 month. Three of these 5 had
      recurrent appendicitis within a year. It is concluded that US can be used not
      only in diagnosing acute appendicitis, but also in the evaluation of treatments
      such as antibiotics.

PMID- 7710800
TI  - Focal fatty masses of the pancreas.
AB  - Five patients with solitary fatty mass of the pancreas examined with CT and
      ultrasound (US) were evaluated. The areas of fat replacement were located in the
      pancreatic neck, body or tail. The size ranged from 4 to 30 mm in the longest
      diameter. The shape varied from roundish, to ovoid to semicircular, and the
      contour was universally well defined. The internal structure was homogeneous in 3
      patients, but in one case there were thin septa and, in another, a slightly
      hyperdense part in the peripheral portion. All the masses except the smallest one
      were in part contact with pancreatic fat. CT showed fat with the same density as
      the peripancreatic fat and low HU units. The mass was hypoechoic in 2 cases and
      hyperechoic in one. The masses in the tail of the pancreas were not detected by
      US.

PMID- 7710801
TI  - Dynamic high-field MR imaging in experimental porcine acute pancreatitis.
AB  - The effects of acute pancreatitis on MR imaging signal intensities (SIs) were
      determined in an experimental study at 1.0 T. Oedematous pancreatitis was induced
      in 9 piglets and haemorrhagic pancreatitis in 11 piglets. Each animal served as
      its own control for MR imaging before and after induction of pancreatitis. T1
      weighted spin echo (450/15 ms) and dynamic turbo FLASH (flip angle 8 degrees)
      sequences were used without contrast medium in testing the stability of the SI
      measurements. There was no significant difference in the SI-versus-time curves of
      the pancreas in piglets with oedematous and haemorrhagic pancreatitis. However,
      the difference in mean SIs between healthy and diseased piglets was significant.
      Thus, although non-contrast MR may be useful in the diagnosis of acute
      pancreatitis, it does not distinguish between oedematous and haemorrhagic
      pancreatitis.

PMID- 7710802
TI  - MR imaging in advanced abdominal pregnancy. A case report of fetal death.
AB  - Abdominal pregnancy is a rare but life-threatening condition. The preoperative
      diagnosis may be difficult. When there is a suspicion of abdominal pregnancy and
      ultrasonographic findings are equivocal or inconclusive, MR imaging should be
      performed. We report a case of an abdominal pregnancy of 28 weeks' gestation
      diagnosed by MR.

PMID- 7710803
TI  - Congenital urethral polyp--a rare cause of infravesical obstruction. A case
      report.
AB  - Urethral polyps are uncommon but may result in infravesical obstruction. A case
      diagnosed by voiding cystourethrogram and sonography is presented.

PMID- 7710804
TI  - Contrast medium-induced vasoconstrictions. An investigation of the
      vasoconstrictive action of iohexol in isolated rabbit coronary arteries.
AB  - Angiographic contrast media (CM) may cause both vasodilatation and
      vasoconstriction. This study evaluates a contrast medium-induced vasoconstriction
      that occurs when isolated arteries are exposed directly to a CM. Segments of
      rabbit coronary arteries were mounted in tissue baths containing buffer solution.
      During the experiments the buffer solution was exchanged with iohexol iso-osmolar
      with plasma, which caused a temporary vasoconstriction of the vessel segments.
      The constriction did not depend on the degree of oxygenation of iohexol. The
      endothelium was not involved in the vasoconstriction. Prazosin slightly decreased
      the vasoconstriction and a small part of the constriction might thus depend on
      liberation of norepinephrine by iohexol. The constriction was totally inhibited
      by the calcium antagonist nifedipine, while it was augmented by addition of low
      concentrations of KCl to ihoexol. It is concluded that the otherwise safe CM
      iohexol causes vasoconstriction in vitro by depolarizing the smooth muscle cells
      and the nerve terminals in the vessel wall.

PMID- 7710805
TI  - Effects on erythrocyte aggregation and blood coagulation from iohexol solutions
      with and without sodium chloride. An in vitro study on the role of ion
      concentration and osmolality.
AB  - Solutions of the nonionic monomeric contrast medium iohexol (300 mg I/ml) with
      and without added NaCl were investigated for effects on red blood cell
      aggregation and blood coagulation. Three volumes of a test solution were mixed in
      test tubes with one volume of human blood. During 30 min samples of the mixture
      were taken for investigation. Six test solutions were used: 1) iohexol, 2)
      iohexol+glucose 280 mM, 3) iohexol+NaCl 150 mM, 4) glucose 280 mM, 5) glucose 140
      mM+NaCl 75 mM, 6) NaCl 150 mM. Test solutions with NaCl caused no aggregation.
      Test solutions without NaCl always caused macroscopic red cell aggregates. These
      aggregates always disappeared when saline was added to the sample. The
      macroscopic red cell aggregates could be dispersed to microscopic aggregates by
      shaking the test tubes. During the next 30 min macroscopic aggregates returned in
      the glucose solution but not in the iohexol solutions. In 30 min, blood mixed
      with iohexol solutions never coagulated while blood layered on top of the same
      iohexol solutions always coagulated. Blood mixed with solutions 5 and 6, both
      without iohexol, always coagulated. It is concluded that adding 150 mM NaCl to
      iohexol did not eliminate its ability to anticoagulate whole blood, but inhibited
      its ability to aggregate red cells. This inhibition was not caused by the osmotic
      effects of the added NaCl.

PMID- 7710806
TI  - Microradiographic anatomy of the explanted rat colon.
AB  - The colon of 32 healthy Sprague-Dawley rats was studied microradiographically.
      The colonic arterial distribution of 18 rats was examined after injecting barium
      sulfate into the isolated aorta. The mucosal surface in 9 rats was studied using
      double-contrast technique after colon explantation. In 5 animals arterial and
      mucosal studies were carried out simultaneously. The radiographic thickness of
      the colonic wall was measured using a comparative microscope. The specimens were
      observed, photographed and examined histologically. Unlike the cecum and distal
      colon which, when insufflated, do not have mucosal folds, the proximal colon
      exhibits folds in an oblique direction corresponding to that of the arteries, and
      the colonic wall in this region is thicker. Comparison between arterial and
      mucosal microradiographic anatomy and wall thickness enables the proposition of a
      simple nontopographic division of the rat colon into cecum, proximal colon and
      distal colon.

PMID- 7710807
TI  - Simple and safe device for pneumatic reduction of intussusception.

PMID- 7710808
TI  - Prenatal development of the rat sinuatrial node.
AB  - In order to study the origin and mode of differentiation of the cells which make
      up the sinuatrial node, samples of the sinuatrial junction of rat embryos of
      different ages were studied by transmission electron microscopy. From a seemingly
      morphologically homogeneous cell population at 11 days, an ultrastructural
      differentiation occurs from day 12. So, one could see: a) irregular-shaped cells
      with dark nucleus and medium-sized contractile apparatus which we have identified
      as ordinary ("working") atrial myocardiocytes and, b) pale cells with a clear
      spheroidal nucleus and cytoplasm containing few organelles and fine myofibrils
      which we have classified as nodal cells. Numerous undifferentiated cells of
      intermediate morphology appear intermingled with nodal and ordinary cells.
      Throughout development, nodal and ordinary cells progressively enhanced their
      mutual differences. Ordinary myocardiocytes become increasingly rich in
      myofibrils and mitochondria, and nodal cells contain scanty organelles and fine
      myofibrils, whereas undifferentiated cells are few at every stage. At the end of
      prenatal life, the sinuatrial node shows numerous unmyelinated axons of immature
      aspect but direct contacts between nodal cells and nerve fibers are not seen. The
      images we obtained suggest that the sinuatrial node must not be taken as an
      embryological remnant. Nodal cells are recognized from the 12th day of embryonic
      life as a particular form of differentiation of the cells which make up the
      sinuatrial region at the preceeding stages.

PMID- 7710809
TI  - Asymmetry in the human skeleton. A study on prehistoric Polynesians and Thais.
AB  - Atlantal, long bone, and craniofacial measurements of prehistoric Polynesian and
      Thai skeletons were analysed to ascertain the extent and direction of bilateral
      asymmetry. The atlantal articular mass was constantly and significantly higher on
      the right side than on the left. In Thais, the midlongitudinal axis of the
      atlanto-occipital facet on the right side had a steeper inclination than that on
      the left. In both groups the dental occlusion was less mesial on the right side
      and the mandible was shorter, significantly so in the Thais. The long bones were
      more asymmetric in the Polynesians than in the Thais. Height asymmetry of atlas
      lateral tuberculum correlated inversely with mandibular ramal width asymmetry.
      Atlanto-occipital facet length asymmetry correlated with asymmetry of the gonial
      angle and facet angulation asymmetry correlated inversely with radial length
      asymmetry. Our results suggest a pervading asymmetry of skeletal structures which
      we ascribe as local adaptations to functional demands rather than as due to a
      uniform asymmetric growth pattern.

PMID- 7710810
TI  - Correlative histochemical and biochemical studies on acetylcholinesterase
      activity during ovulation in the rat.
AB  - A correlative histochemical and biochemical study has been made of the changes in
      acetylcholinesterase (AChE)-positive sites during ovulation induced in immature
      female albino rats with exogenous gonadotrophins. Acetylcholinesterase is the
      marker for cholinergic innervation. In histochemical observations, AChE+ve sites
      were localized in typical perivascular position and the intensity and number of
      enzyme-positive sites around the Graafian follicle gradually increased during
      follicular maturation and ovulation but stromal AChE-activity did not show any
      appreciable change. Biochemical estimation of the enzyme supports these
      observations. The electronmicroscopic and histological observations of the
      structural changes in nerves accompanying ovulation have also been enumerated and
      the role of cholinergic nerves in neuromuscular control of ovulation is
      discussed.

PMID- 7710811
TI  - A scanning and light microscope study comparing the effects of clomiphene
      citrate, estradiol 17-beta and progesterone on the structure of uterine luminal
      epithelial cells.
AB  - Scanning electron microscopy was used to evaluate the surface ultrastructure of
      uterine luminal epithelial cells from ovariectomized rats treated with either,
      high or low doses of Clomiphene citrate or estradiol-17 beta or progesterone
      given on consecutive days. Light microscopy was used to evaluate the surface
      epithelium and morphometric methods were used to measure cell height. It was
      found that clomiphene treatment produced ultrastructural surface features some of
      which were similar to those seen with hormone treatments and others unique to
      clomiphene alone. Features reminiscent of oestrogen treatment include hyperplasia
      and hypertrophy of the luminal epithelium, an increase in the length and density
      of microvilli and the formation of gland "hillocks". Features reminiscent of
      progesterone treatment include the development of pinopods and secretion
      droplets. Features unique to clomiphene treatment include possible stratification
      of the luminal epithelium, the presence of surface lesions, irregular and
      doughnut shaped cells, areas of microvilli free plasma membrane and an increase
      in cell height when compared to the effects of oestrogen and progesterone. It is
      clear that the effects of clomiphene are both dose and duration dependent; and
      that some of the morphological features elicited with clomiphene treatment are
      similar to those seen with the hormone treatments. Overall clomiphene induced
      features are different to those elicited with either of the hormone treatments
      tested.

PMID- 7710812
TI  - 3D spatial relationships of histochemical activity in the rat superior
      colliculus.
AB  - Recent evidence points to the existence of lattices of acetylcholinesterase
      (AChE) and cytochrome oxidase (CYO) in deep layers of the superior colliculus. We
      sought to further describe their localization within the rat superior colliculus
      using new three dimensional (3D) digital imaging techniques. Texture maps of AChE
      staining within the stratum griseum intermediate (SGI) suggest a sheet of high
      enzyme activity punctuated by areas of pallor. This lattice of dense staining
      covered the caudal end of the colliculus and extended rostrally along the medial
      bank. Discrete regions of low staining were most apparent within the IVc
      subdivision of SGI. A similar examination of CYO activity failed to reveal any
      compartmentalization.

PMID- 7710813
TI  - Effects of cis-dichlorodiammineplatinum on the molecular layer interneurons of
      the immature rat cerebellum: a putative role for calcium.
AB  - The administration of cis-dichlorodiammineplatinum to rats at 10 days of
      postnatal life (PD 10) alters the immunoreactivity for parvalbumin of the
      interneurons of the cerebellar molecular layer at late post-treatment intervals.
      This can result in, but may be also a consequence of the elevation in the
      cytosolic calcium concentration. Changes in the intracellular calcium homeostasis
      may induce damage of the cytoskeletal apparatus and impair growth of the cell
      processes leading to alteration of the ultrastructure of the cell.

PMID- 7710814
TI  - History of development and applications of nuclear analytical methods in the
      Czech Republic.

PMID- 7710815
TI  - Proceedings of the International Conference on Nuclear Analytical Methods in the
      Life Sciences. Prague, 1994.

PMID- 7710816
TI  - Effects of target temperature on analytical sensitivities of cold-neutron capture
      prompt gamma-ray activation analysis.
AB  - Cold-neutron prompt gamma-ray activation analysis sensitivities are often
      decreased because of an increase in the average neutron energy on scattering
      within room temperature targets. Experiments were performed to determine whether
      target cooling would alleviate these effects. Cooling the targets to 77 K
      increased hydrogen sensitivity by as much as 25%. Target cooling decreases those
      effects of neutron scattering on CNPGAA sensitivities that are the result of an
      increased average neutron energy. However, cold-neutron scattering may also
      change the average path length traveled, and this effect on sensitivity is not
      alleviated by controlling temperature.

PMID- 7710817
TI  - Use of 191Pt radiotracer for the development of enrichment procedures to detect
      natural levels of platinum in biological and environmental materials.
AB  - The 191Pt-radiotracer is a powerful tool to develop separation and
      preconcentration methods for Pt. The radiotracer was produced either through
      190Pt (n, gamma) 191Pt reaction on Pt enriched in 190Pt, or through 191Ir (p,n)
      191Pt reaction on natural Ir, followed by Pt/Ir separation. The solvent
      extraction behavior of 191Pt(IV) from HCl with tributylphosphate, rubeanic acid
      in tributylphosphate and thenoyltrifluoroacetone in n-butylalcohol/acetophenone,
      followed by back-extraction with 2 mol/L NH4OH was studied. The overall recovery
      from a biological matrix is up to 80%. Trace amounts of 191Pt were also
      preconcentrated as bis-(carboxymethyl) dithiocarbamate chelates on an XAD-4
      microcolumn and eluted with EtOH/1 mol/L HNO3. More than 80% is recovered in 2 mL
      or about 70% in 300 microL.

PMID- 7710818
TI  - Determination of cobalt in biological samples by radiochemical neutron activation
      analysis employing reverse-phase chromatography.
AB  - We report the final part of our "on-line yield" pilot program in this article.
      This last part deals with aspects of accuracy and precision of the determination
      of cobalt in biological materials by RNAA with on-line yield determination. To
      obtain an insight into the accuracy of the technique, certified reference
      materials were analyzed, and for selected materials, results obtained by INAA and
      RNAA of identical samples have been compared. It shows that the mineralization in
      our RNAA scheme may be a sample-related source of systematic errors that is not
      related to the presence or absence of HF. Finally, we present some critical notes
      on pros and cons of the practice of on-line yield concept and some ideas for
      further research.

PMID- 7710819
TI  - Advanced short-lived nuclide NAA with application in the life sciences.
AB  - A new technique for short-lived nuclide activation analysis has been developed
      that compensates the rapid radioactive decay during the counting period by
      simultaneous approach of the sample holder to the detector with a mechanical
      device, permitting prolongation of the counting time and reduction of the
      required complementary cyclic activation to avoid sample container damage. The
      operation of the analytical system is automated by a programmable logic
      controller (PLC). This improvement of short-lived nuclide activation analysis,
      providing a high throughput, is important in biological and environmental
      research, where often a large number of samples has to be analyzed for sufficient
      sampling statistics.

PMID- 7710820
TI  - Application of nuclear analytical techniques using long-life sealed-tube neutron
      generators.
AB  - The new range of sealed-tube neutron generators developed by SODERN appears to be
      appropriate for the industrial environment. The main characteristics are the high
      emission stability during the very long lifetime of the tube, flexible pulsed
      mode capability, safety in operation with no radiation in "off" state, and the
      easy transportation of equipment. Some applications of the neutron generators,
      called GENIE, are considered: high-sensitivity measurement of transuranic
      elements in nuclear waste drums, bulk material analysis for process control, and
      determination of the airborne pollutants for environmental monitoring.

PMID- 7710821
TI  - Optimization of irradiation conditions for photon activation analysis of
      biological and environmental samples using a high power electron accelerator.
AB  - Using the bremsstrahlung flux density data of Tanaka et al. (1983), the PHOTAC
      code has been developed to calculate the activity induced in a sample during
      photon activation as a function of the geometrical arrangement of the electron
      energy and the beam profile. Some results are given for sample volumes from 1 to
      1000 cm3 and sample distances from 1 to 10 cm at 25 MeV. Examples for the
      application of the PHOTAC code to estimate the maximum activity output and to
      minimize the heating up of the sample during irradiation are discussed.

PMID- 7710822
TI  - Use of nuclear analytical techniques in bioenvironmental studies.
AB  - Bioenvironmental studies remain to be one of the most important fields of applied
      analytical chemistry. At present time, more than 50% of nuclear analytical
      studies deal with bioenvironmental investigations. The first period of utilizing
      nuclear analytical methods in bioenvironmental sciences could be characterized as
      "purely analytical," in which these methods were used for determination of sample
      composition in competition with other non-nuclear methods. Later, the outstanding
      advantages of the former methods were used for more detailed description of
      systems to be studied, including element speciation, spatial distribution, and so
      forth. The present period not only develops approaches of previous periods but
      also considers the bioenvironmental processes more widely and is focused on their
      dynamics. In this field, a large extent of utilizing various nuclear analytical
      techniques can be expected as well.

PMID- 7710823
TI  - Nuclear analytical techniques in environmental studies.
AB  - Nuclear analytical techniques are particularly suitable for measuring trace
      components in a wide variety of environmental samples, and for that reason, the
      techniques have made a significant contribution to environmental research.
      Presently, at a time when biosphere contamination and threats of global change in
      the atmosphere are of widespread concern, there exist an impressive array of
      specialized instrumental methods available to life scientists engaged in
      environmental studies; however, the nuclear techniques will probably continue to
      play a useful role in the future, notwithstanding the decreasing availability of
      necessary facilities, such as research reactors and accelerators. Reasons for the
      particular suitability of radionanalytical techniques are reviewed and
      illustrated by examples of recent applications to solid wastes, biomonitoring,
      and urban aerosol source identification in this laboratory.

PMID- 7710824
TI  - Studies of incinerator ashes and environmental effects using radioanalytical
      techniques.
AB  - We have studied solid waste incinerator ashes to understand the leaching
      mechanism and speciation of toxic and other elements in them. Leaching media,
      such as water and acetate buffer, at various pHs were used. Incinerator ashes
      generally contain concentrations of many toxic elements, such as Cd, As, Hg, and
      Se. These elements are leached out rather easily. Many of the elements are
      leached within the first few minutes to an hour, and the majority of the elements
      reach peak equilibrium concentrations within 200 h. The pH and nature of the
      leaching medium are important factors in the leaching of the elements.

PMID- 7710825
TI  - Study of a low-selenium environment in China by INAA and Mossbauer spectrometry.
AB  - The neutron activation analysis, gamma coincidence spectroscopy, nondispersive
      hydrogen flame atomic fluorescence spectroscopy, and Mossbauer spectrometry were
      used to study the low-selenium environment of the Exi Autonomous Prefecture, a
      well-known Keshan disease region. The Se contents in the soil samples there range
      from 0.075-0.18 mg/kg with the average of 0.13 mg/kg, whereas in the maize from
      0.001-0.018 mg/kg with the average of 0.0099 mg/kg. The 57Fe Mossbauer spectrum
      of the soil indicates an anoxic environment. In addition to the FE3+ species the
      compounds containing low-valence iron e.g., goethite, and so forth, also exist.
      The rare earth element (REE) pattern obtained by NAA further confirms the
      reductive soil environment, which causes the selenium deficiency.

PMID- 7710826
TI  - Analysis of membrane filters and thick fly ash samples by PIXE.
AB  - The possibility of the routine PIXE measurement of environmental samples has been
      tested at the INP in Rez. Both thin samples of aerosols collected on membrane
      filters Synpor and Nuclepore and thick aerosols and fly ashes samples pressed
      into pellets were analyzed. The Nuclepore filter was found more suitable for PIXE
      analysis of aerosols than the Synpor, and the thin aerosol sample analysis was
      found to be easier than the thick sample analysis. The grain size effect in the
      case of thick fly ash samples is discussed.

PMID- 7710827
TI  - Use of k0-NAA in the life sciences.
AB  - The applicability and usefulness of k0-based reactor neutron activation analysis
      (NAA) in the life sciences is evaluated from the following examples: 1.
      Instrumental NAA of NIST SRM 1633a coal fly ash, as a quality assessment; 2.
      Radiochemical NAA of Versieck's reference human serum, and--herewith associated-
      the development of practical correction procedures for neutron-induced reaction
      interferences and of improved methods to evaluate the detection efficiency and
      the correction for true coincidence; and 3. Determination of the lanthanides in
      plant leaves and lichens near a Portuguese coal-fired power station, which led to
      the introduction of the Westcott formalism and to the use of a low-energy photon
      detector. As concluded, k0-based NAA is at present capable of tackling a large
      variety of analytical problems when it comes to the multielement determination in
      environmental and biological matrices.

PMID- 7710828
TI  - Rubidium and cesium in spruce needles. Concentrations and biodynamics.
AB  - The endogenous concentrations of Rb and Cs have been determined in needles of 56
      trees (Norway spruce, Picea abies) from eight different sites. Analysis was done
      by instrumental neutron activation. Concentrations were found to have a very
      large range (3-28,000 ng Cs/g and 1-190 micrograms Rb/g). The values on a given
      site have a tendency toward a log-normal distribution. There is a significant
      correlation between Rb and Cs, but the correlation is not linear. The
      concentrations of both elements are a function of the needle age. They decrease
      smoothly, approaching a constant value, when going from needle age class 1 to 5.
      It is shown that one algebraic function describes this biodynamic behavior on all
      sites and at all concentration levels. The function and its parameters are
      discussed.

PMID- 7710829
TI  - Heavy metals in Parmelia sulcata collected in the neighborhood of a coal-fired
      power station.
AB  - The epiphytic lichen Parmelia sulcata was collected in the neighborhood of a
      Portuguese coal-fired power station (Sines coal power station) as monitor for
      heavy metal air pollution. A study of the metal contents variability along 1991
      and 1992 was performed. The heavy metals Ag, As, Br, Co, Cr, Fe, Hg, Sb, Se, and
      Zn were determined by k0-based instrumental neutron activation analysis. The
      concentrations found in 1991 and 1992 show an accumulating process of Co and Fe
      (approximately 5%/mo) and of Cr and Sb (approximately 7%/mo). Low accumulation is
      observed for Ag, Se, and Zn (approximately 2%/mo), and no concentration variation
      is observed for As, Br, and Hg. It is concluded that the metal accumulation
      observed is the result of the nearby ash and coal deposits.

PMID- 7710830
TI  - Metal determination by EDXRF in lichens. A contribution to pollutants monitoring.
AB  - Samples of Evernia prunastri, collected in a mountainous zone, were exposed in
      urban and highly industrialized areas in order to monitor the atmospheric
      pollution. Amounts of Cr, Mn, Fe, Ni, Cu, Zn, and Pb were determined by EDXRF
      spectrometry in secondary target excitation mode and in the thin film approach.
      An increase in metal concentrations was noted on all sites with time exposition
      increases, but the highest final amounts were observed on those thalli mounted
      near a steel works. The washing procedure influenced the concentration of all the
      elements as previously verified on Pseudevernia furfuracea.

PMID- 7710831
TI  - Energy-dispersive X-ray fluorescence analysis applied to biomonitoring on Alps.
AB  - The results of a research in progress at the Istituto di Fisica Generale
      Applicata--University of Milan--on natural and anthropogenic elements'
      determination in mosses as biological indicators are shown. The analytical
      technique was the energy dispersive X-ray fluorescence (EDXRF) spectrometry. The
      chosen areas for a preliminary pollution mapping were Italian Central Alps
      (Valmalenco and Valtellina) and the hills around Como (pre-Alps); in addition, a
      group of mosses was from Monza Park, near Milan.

PMID- 7710832
TI  - A survey of trace elements in fresh-water fish and rice along the Han River by
      neutron activation analysis.
AB  - For a case study of environmental pollution, radiochemical neutron activation
      analysis (RNAA) was applied to the crucian and rice collected along the Han
      River. The crucian was analyzed for three times in 1973, 1987, and 1990. Sixteen
      trace elements (Hg, Cd, As, Br, Cu, Na, K, Se, Cr, Hf, Rb, Fe, Zn, Co, La, and
      Cs) were determined by RNAA using distillation and diethyldithiocarbamate
      extraction methods. Contents of Na, K, Se, Hf, Fe, Zn, and Co were almost
      constant regardless of the sampling place and year. The contents of the other
      elements showed increasing trends down river, especially in the first
      investigation. At the lower part of the river, the contents showed decreasing
      trends with the time of sampling, especially during the first two investigations.
      These trends were typical for Hg and Cd. Rice was analyzed by the same method for
      12 elements, and the results showed no regional trends, but have decreased after
      1973.

PMID- 7710833
TI  - The accumulation and distribution of trace metals in some localized marine
      species.
AB  - Trace elements, such as As, Co, Cr, Hg, Sb, and Zn, were determined by neutron
      activation analysis (NAA), whereas Cd, Cu, and Pb were determined by graphite
      furnace atomic absorption spectroscopy (GFAAS) in clam, crab, prawn, swamp
      cerith, and mussel samples after digestion by microwave heating under controlled
      conditions before eluting the solutions through a column of a chelating resin,
      Chelex-100. The standard used in the determination of percentage volatile
      elements retained by microwave digestion and also in the activation process was
      Lobster Hepatopancreas TORT-1, whereas known mixed standards were prepared from
      nitrate salts to determine the efficiency of the separation procedure at a
      controlled pH. Mercury and lead detected in crabs exceeded the maximum
      permissible level. Some species also showed a high affinity toward certain
      elements, and their levels of accumulation in the tissues of these species
      corresponded with the concentration of these elements in sediments, especially at
      sites in the vicinity of an industrial zone.

PMID- 7710834
TI  - Determination of antimony in natural waters by preconcentration on a chelating
      sorbent followed by instrumental neutron activation analysis.
AB  - Antimony was preconcentrated from natural waters on thionalide-loaded acrylic
      polymer (Bio-Beads SM-7) from 0.5 m HCl solution. Prior to the preconcentration,
      Sb(V) was reduced to Sb(III) with potassium iodide. The antimony retained on the
      resin was determined by neutron activation and gamma-spectrometric measurement of
      122Sb (564 keV). The lower limit of detection was 0.023 micrograms/L for a 100-mL
      sample.

PMID- 7710835
TI  - Investigation of element speciation in atmosphere.
AB  - Elemental composition of rain water was determined with the use of instrumental
      neutron activation analysis. Solid water-insoluble fractions were separated by
      filtration through membrane filters. Filtrates were dried, and dry residues as
      well as solid-phase on filters were analyzed. Concentrations of 20 elements in
      the samples were determined. Enrichment factors and ratios between element
      concentrations in liquid and solid fractions were calculated. Data obtained
      allowed us to suppose that Na, Cl, K, Sc, Cr, Mn, Fe, Se, Br, I, Cs, La, Sm, and
      Au prevalently exist in the air in the form of relatively coarse aerosol
      particles; Zn, As, Sb, and Hg prevalently occur in the vapor-gas phase; and Co
      and W, in the form of finely dispersed aerosol.

PMID- 7710836
TI  - Determination of heavy metals in humic substances by instrumental photon
      activation analysis.
AB  - Photoactivation analysis is used for the determination of heavy metals in water
      and humic substances. Isolated humic acids serve as a carrier of environmental
      pollutants. The investigation of the drinking water catchment area in the middle
      German conurbation Leipzig/Halle shows it to be endangered from old neglected
      deposits of toxic wastes (chemical factory destroyed during World War II).
      Elevated concentrations of the elements zinc, cadmium, lead, and mercury in humic
      acids from surface waters were found.

PMID- 7710837
TI  - Accumulation of cesium and radiocesium in forest litter in selected regions of
      Poland and its influence on litter-to-mushroom transfer factor.
AB  - The aim of this work was to check whether the stable cesium content in forest
      litter affects the value of radiocesium from litter-to-mushroom transfer factor
      Tf or not. Total cesium in litter, measured by AAS, varied from 0.1-2.7
      micrograms/g. These data, combined with earlier results for mushrooms, showed no
      simple correlation for Tf. More complex relationships provided very high
      correlation coefficients, but their validity needs further investigation.

PMID- 7710838
TI  - The radioanalytical laboratory at Pelindaba. Some applications for environmental
      and health monitoring.
AB  - This article deals with the radioanalytical work performed at Pelindaba, Atomic
      Energy Corporation of South Africa. It reports on the activities of a commercial
      laboratory, employing analytical techniques, such as total alpha/beta counting,
      alpha spectrometry, liquid scintillation counting, gamma spectrometry, and
      neutron activation analysis. Techniques discussed in more detail include
      semicyclic activation analysis for the determination of fluorine in vitamin
      mixes, as well as the determination of uranium and radium in urine samples for
      personnel monitoring.

PMID- 7710839
TI  - Application of nuclear analytical methods in the investigation and identification
      of new selenoproteins.
AB  - Nuclear methods have been applied in the investigation of selenium-containing
      proteins in rat tissues. Selenium was determined in tissues, cells, and cellular
      compartments by instrumental neutron activation analysis via 77mSe or 75Se. For
      tracer studies, the selenium compounds were labeled in vivo by administering 75Se
      with a high specific activity to rats. Quantitative determination of very small
      amounts of the element in protein fractions was achieved by measurement of the
      tracer after replenishment of selenium-depleted animals with the labeled element.
      The application of the nuclear methods in the detection, characterization, and
      identification of new selenium-containing proteins is shown with the help of some
      examples.

PMID- 7710840
TI  - Detection and determination of selenoproteins by nuclear techniques.
AB  - Microbeam X-ray spectrometry, energy-dispersive X-ray fluorescence analysis, and
      neutron activation analysis were evaluated for the detection of selenium
      contained in the selenoprotein glutathione peroxidase. The glutathione peroxidase
      had been previously separated using polyacrylamide gel electrophoresis. The use
      of Bragg-reflected polarized X-ray beams was employed in the X-ray fluorescence
      measurements to minimize the problem of scatter owing to the gel matrix. Current
      detection limits of selenium in a gel matrix are 2.1 ng in the bench-top
      microbeam X-ray system and 30-60 ng using XRF with polarized beams. Neutron
      activation analysis was used for quality-control measurements, with a detection
      limit here of < 0.08 ng. The work has in principle established the feasibility of
      such an approach.

PMID- 7710841
TI  - A study on children's condition thalassemia using neutron activation analysis and
      other techniques.
AB  - In this study, 50 thalassemia patients were tested using dual-energy X-ray
      absorptiometry (DEXA) and in vivo neutron activation analysis (IVNAA) to
      determine their bone mineral status. Both techniques were suitable for this
      purpose. Lower age was found to correspond to lower liver iron content and higher
      bone mineral content in the normal range. Patients undergoing treatment with
      transfusion had higher bone mineral content. Osteopenic patients had higher
      hepatic iron content than those with normal bone status. In the case of DEXA,
      bone mineral content (BMC) divided by height cubed was found to be a better
      indicator of bone mineral status than the BMD usually given. Liver density as
      determined by DEXA correlates well with hepatic iron.

PMID- 7710842
TI  - Kinetics of elemental content changes of bone tissue of mice during evolution
      under hypokinetic stress.
AB  - Concentration of 13 elements in bone tissue of mice held in tightly spaced cages
      for 3 wk, which caused an acute stress reaction, was determined by means of
      neutron activation analysis. Functionally different bone tissues of mice
      skeletons--the femur, accomplishing both supporting and dynamic functions; the
      parietal bone, being practically immovable; and the ectopic bone, newly formed
      under kidney capsule in the place of syngeneic bone marrow implantation--were
      analyzed. Similar dynamics of the elemental composition of investigated bones was
      found: the progressive demineralization owing to the loss of Ca, P, Mg, and Fe is
      accompanied by the compensatory inclusion of Sr in the bone tissues. In the
      ectopic bone, it was not as high. During evolution under hypokinetic stress, the
      microelement concentrations (Zn, Cr, Rb, Ru, Br, Co, Sb) change significantly.
      Results obtained form the evidence for some system character of osteoporosis at
      limited mobility.

PMID- 7710843
TI  - Determination of sodium-to-calcium ratio in mouse femora by INAA.
AB  - Within the scope of the study of the heteroionic exchange in the bone mineral,
      the sodium-to-calcium ratio was established in femora of 55 male ICR mice. The
      purpose of the work was to establish the precision of the method as well as
      biological variations, since the authors intend to investigate the sodium-to
      calcium ratio on pathophysiological models in the future with a special regard to
      osteoporosis. The resulting mean value was of 0.02515 +/- 0.00053. The small
      standard deviation indicates that the ratio is not subject to considerable
      individual variations. The accuracy of the method was checked by analyzing the
      reference bone sample IAEA H-5. The results obtained exerted a good agreement
      with the certified sodium and calcium concentrations.

PMID- 7710844
TI  - Vanadium levels in urine and cystine levels in fingernails and hair of exposed
      and normal persons.
AB  - Vanadium was determined by radiochemical neutron activation analysis (RNAA) with
      proven accuracy in urine of workers occupationally exposed to vanadium-rich dust
      in a vanadium pentoxide production plant, and values in the range of 3.02-762
      ng/mL (median 33.0 ng/mL) were found. In a control group consisting of
      administrative workers of the plant, urinary vanadium levels were found in the
      range of 1.05-53.4 ng/mL (median 2.53 ng/mL), whereas in an another control group
      of occupationally nonexposed persons, these values amounted to 0.066-0.489 ng/mL
      (median 0.212 ng/mL). Accuracy of the results was tested by analysis of reference
      material IAEA A-13 Animal Blood and NIST SRM-1515 Apple Leaves, and very good
      agreement was found with literature and the NIST certified values, respectively.
      Unlike urine, no significant differences were found for cystine levels in
      fingernails and hair of exposed and control persons.

PMID- 7710845
TI  - Application of short-lived radionuclides in neutron activation analysis of
      biological and environmental samples.
AB  - The application of short-lived nuclides, especially in connection with the 6LiD
      converter, in biological and environmental samples is demonstrated on I and Br
      determination in human urine, on I in pet food, and on the analysis of all the
      halogens in volcanic gases in a single activation. Trace element determination in
      lichens indicates polluted and unpolluted areas. The use of the .74-s 38mCl
      enables the rapid screening of great number of samples.

PMID- 7710846
TI  - Hair trace elements in kidney dialysis patients by INAA.
AB  - INAA was used to determine selected trace elements--Ca, Al, P, and S--in 104
      cleaned scalp hair samples from kidney dialysis patients (n = 54) and healthy
      controls (n = 50) in order to explore any differences in these elements that
      might be related to prolonged dialysis and/or associated medication in comparison
      with blood serum levels of Al and P measured in the same clinic at the time of
      hair sampling. After correction for P (and Si) interference in Al content, it was
      observed that there were no significant differences (at 95% confidence level) in
      hair Al and Ca, which had been expected, whereas while there were definite
      increases in P and S. Multivariant factor analysis applied to the same data set,
      however, showed some multiple correlations among four variables: serum Al,
      duration of dialysis, medication, and hair Al.

PMID- 7710847
TI  - Determination of platinum by neutron activation analysis in nerve tissue from
      rats treated with cisplatin.
AB  - The analytical method used for the determination of traces of platinum and gold
      in different tissues of Wistar rats is based on neutron activation analysis with
      radiochemical separation of gold. This separation is performed by electrolytic
      deposition of gold on a niobium cathode, which ensures the highest radiochemical
      purity without any spectral interference from calcium or other major elements.
      Corrections for the nuclear interference from double neutron capture, caused by
      the gold content of the samples, were found to be insignificant at the levels
      reported. The following neural tissues were analyzed for their content of
      platinum: the dorsal root ganglions as well as the dorsal and ventral part of the
      spinal cord. The highest level of platinum was found in dorsal root ganglions.

PMID- 7710848
TI  - Study of trace elements in blood of cancer patients by proton-induced X-ray
      emission (PIXE) analysis.
AB  - Proton-induced X-ray emission (PIXE) analysis was employed to determine the
      concentrations of six elements in the plasma and erythrocytes of 18 cancer
      subjects (15 males and 3 females) with neoplastic disorders and in 70 controls
      (35 males and 35 females). It was found that the concentrations of Br, K, and Zn
      were significantly elevated in the erythrocytes of the cancer subjects compared
      to the controls, whereas the concentration of Fe was significantly depressed, but
      with no difference observed in the concentration of Ca. In the plasma, the
      concentrations of Br, Cu, Ca, and K were significantly elevated, whereas the
      concentrations of Fe and Zn were found to be significantly depressed compared to
      the controls.

PMID- 7710849
TI  - Elemental concentrations in nigerians with affective disorders using proton
      induced X-ray emission.
AB  - The concentrations of a number of elements are determined in the plasma and
      erythrocytes of 21 Nigerians (11 females, 10 males) with symptomatic affective
      disorders (11 depressives, 10 manics) and in 40 normal controls using proton
      induced X-ray emission (PIXE) analysis. The study shows that there is significant
      elevation of plasma K and Zn, as well as the erythrocyte S in the patients
      relative to the controls. The plasma and erythrocyte Cu, and the erythrocyte P,
      Ca, Fe, and Zn are significantly lower in the patients compared to the controls.
      However, the plasma levels of Ca, S, Fe, and Br are similar in both the patients
      and the controls. Similarly, the concentrations of K, Br, and Rb show no
      significant difference in the erythrocytes of patients and controls.

PMID- 7710850
TI  - Trace element content in breasts with fibrocystic disease.
AB  - The trace elements antimony, bromine, cesium, cobalt, iron, rubidium, scandium,
      strontium and zinc were determined by instrumental neutron activation analysis in
      breast tissue samples with fibrocystic disease and in samples with fibroadenoma
      tumors. The histological lesions of each breast sample with fibrocystic disease
      were recorded, and a statistical analysis of the lesions in combination with the
      determined trace elements was carried out. The results showed that the element
      mean values in fibroadenoma tumors are higher than those of fibrocystic disease.
      Some other remarkable results of statistical examination are also presented.

PMID- 7710851
TI  - Mapping using human blood composition data.
AB  - The mapping of elemental composition using INAA on the base of whole blood and
      hair of inhabitants (2500 samples) was made in Uzbekistan (CIS). The average
      concentrations of 15 elements (24 for hair) were determined. The results obtained
      were compared to regional medical statistics. The correlations for various
      diseases were obtained. The maps of human blood composition in comparison to
      those for human hair composition seem to be less significant in terms of regional
      contamination (probably because of stronger homeostatic control of blood). On the
      other hand, specific changes of blood composition were detected for some
      occupational groups. Relationships of blood and hair elemental composition and
      their relative significance are discussed.

PMID- 7710852
TI  - Determination of trace elements in normal and diabetic whole blood by neutron
      activation analysis.
AB  - The concentration of 10 trace elements in samples of normal and diabetic whole
      blood were investigated by neutron activation analysis (NAA). Instrumental NAA
      (INAA) was used for determination of Co, Cr, Hg, Rb, Se, and Zn, whereas NAA with
      radiochemical separation (RNAA) was employed for determination of Al, Cu, Mg, and
      Mn. The results for normal blood compare well with literature values. Co, Cr, Se,
      and Zn show lower values in diabetes than in the normal blood samples.

PMID- 7710853
TI  - Changes of concentrations of the elements Co, Cr, Sb, and Sc in tissues of
      persons with joint implants.
AB  - Elevated levels of Co and Cr were found in several organs of decreased implant
      bearers (CoCr-alloy/polyethylene joint prostheses) by means of instrumental and
      radiochemical neutron activation analysis as compared to normal persons. For
      comparative purposes, concentrations of the elements Co, Cr, Sb, and Sc were
      measured in heart, kidney, liver, and spleen of the patients and normal persons.
      For Cr determination, a new radiochemical separation technique with sufficiently
      low determination limit was employed. The importance of such investigations for
      studying possible carcinogenic effects of corrosion products and wear particles
      of metallic prostheses is mentioned.

PMID- 7710854
TI  - Analysis of elemental absorption and excretion in mice bearing malignant ascites.
AB  - Feces, kidney, and small intestine were sampled from the mice bearing malignant
      ascites at different stages of tumor growth to investigate the kinetics of
      elemental distribution in the body. The contents of 14 elements in samples were
      determined by instrumental neutron activation analysis (INAA). The elements Br,
      Cl, Cu, Na, Se, and Zn increased, whereas Mn and Rb decreased in kidney with the
      growth of the tumor. The elements Cl, Na, and Fe, however, appeared to have
      significantly different behavior in the small intestine.

PMID- 7710855
TI  - Neutron activation analysis for the determination of trace elements in biological
      materials.
AB  - Neutron activation analysis, in both its radiochemical and instrumental forms, is
      a precious technique for the determination of trace elements in biological
      materials. Probably its most important advantage is its relative freedom from
      errors resulting from contamination of the samples. Invaluable characteristics
      are also its excellent sensitivity, outstanding selectivity, and remarkable
      multielement capability. It is, however, necessary to warn against uncritical
      expectations. This is best illustrated by the seriously inconsistent results
      obtained in several laboratories. Because of the necessity to have access to a
      nuclear research reactor, the stringent safety rules to be observed, the rather
      high costs of the analyses, the relatively low sample throughput, and the
      sometimes long delay between the taking of a sample and the obtaining the final
      result, the use of neutron activation analysis remained restricted to a few-
      essentially research--laboratories. It found its main application in solving
      arduous problems and in paving the way for other analytical techniques better
      suited to routine applications.

PMID- 7710856
TI  - Toxic heavy metals and other trace elements in foodstuffs from 12 different
      countries. An IAEA coordinated research program.
AB  - A research program related to the assessment of toxic heavy metals and essential
      trace elements in foodstuffs has been carried out in 12 countries under the
      auspices of the IAEA. The main purpose of this program was to obtain data on the
      elemental concentrations of potentially toxic elements in foodstuffs in various
      countries, and to compare them with the maximum permissible levels specified in
      national legislation and international guidelines. High-priority elements for
      this study were As, Cd, Cr, Pb, Hg, and Se. Also of interest, but of lower
      priority, were Sb, Cu, and Zn. Emphasis was placed on the use of nuclear and
      nuclear-related analytical techniques, complemented by conventional methods, and
      on quality assurance.

PMID- 7710857
TI  - Total and methyl mercury levels in human scalp hairs of typical populations in
      China by NAA, GC(EC), and other techniques.
AB  - The contents of total and methyl mercury in scalp hair samples of 1179 fishermen
      living in a typical Hg-polluted region in northeast China and 27 lying-in women
      and their newborns in Beijing have been determined by INAA, GC(EC), and other
      techniques. Only 18 of all fishermen had Hg contents above 5 micrograms/g, which
      indicates that the Hg pollution there has been substantially alleviated. The
      longitudinal Hg patterns of the lying-in women showed a gradually lowering
      tendency during pregnant period. Further, the Hg contents of the newborn babies
      generally were above or close to those of their mothers, confirming the mechanism
      that the methyl Hg, an organic species of Hg with high toxicity, is readily able
      to penetrate the placental barrier and to accumulate in the fetus. Thus, the
      mercury poison has occurred at the early stage of pregnancy.

PMID- 7710858
TI  - Mercury determination in hair of Malaysian fishermen by neutron activation
      analysis.
AB  - Fish has been known as a source of nonoccupational mercury exposure to fish
      consuming population groups. In this study, hair samples collected from fishermen
      and their families residing in an industrialized area in Penang and a
      nonindustrialized area in Terengganu were analyzed for mercury by neutron
      activation. The range, arithmetic mean, geometric mean, and median of the mercury
      concentrations for the groups in Penang and in Terengganu were 0.45-16.68, 3.61,
      3.49, and 2.96 and 6.79-18.31, 12.08, 11.69, and 12.05 mg/kg, respectively.
      Somewhat lower values than from the Penang group were found in a group from
      Selangor consisting mainly of office workers. The group in Penang took about 40
      100 g of fish/d, whereas the group in Terengganu consumed twice as much. This
      shows that hair mercury levels depend on a fish consumption pattern, and not on
      the location of the population. The levels of mercury found in this study were
      similar to those reported by other workers for fish-consuming population groups
      worldwide.

PMID- 7710859
TI  - Elemental composition of head hair and fingernails of some Nigerian subjects.
AB  - In this article, we present the elemental concentrations determined by INAA for
      30 elements measured in some or all head hair samples of 100 Nigerian subjects
      and 20 elements in the fingernails of some of the same subjects. Measurements of
      the skewness of the distribution of each element in both tissues confirm previous
      reports that many tend toward a log-normal distribution. Thus, their
      concentrations in the tissues may not be under any homeostatic control. The
      ranges of elemental concentrations together with the medians, and the arithmetic
      and geometric means, with their respective standard deviations are presented and
      compared with literature values for other populations. Correlations between
      elements detected in hair are also sought.

PMID- 7710860
TI  - Correlations between trace element levels in head hair and blood components of
      Nigerian subjects.
AB  - Elemental concentrations in head hair and blood (whole-blood, erythrocytes and
      plasma) of 28 Nigerian subjects were determined using instrumental neutron
      activation analysis (INAA) and proton-induced X-ray emission (PIXE) techniques.
      Correlations found between different elements in hair and blood are reported.
      Hair levels of both zinc and chlorine were found to be significantly correlated
      with their levels in erythrocytes.

PMID- 7710861
TI  - Baseline levels of elemental concentrations in whole blood, plasma, and
      erythrocytes of Nigerian subjects.
AB  - In this pioneering effort on Nigerians, the arithmetic means, ranges, and
      standard deviations for the concentrations of the 13 elements, Br, Ca, Cl, Cu,
      Fe, K, Na, P, Pb, Rb, S, Se, and Zn, detected in freeze-dried whole blood,
      erythrocytes, and plasma of 120 subjects drawn from different geographical
      regions of Nigeria are reported. Elemental analyses have been carried out largely
      using instrumental neuron activation analysis (INAA) with both proton-induced X
      ray emission (PIXE) and graphite furnace atomic absorption spectrometry (AAS)
      serving as complementary techniques. Our values, compared with similar data from
      other parts of the world, show a general good agreement. Values in male and
      female subjects are compared. Correlations between different elements are also
      noted.

PMID- 7710862
TI  - Analytical applications of guided neutron beams.
AB  - Guided beams of thermal and cold neutrons have become available to analysts at
      several reactors during the past decade. The very pure beams from these guides
      have led to lower backgrounds and higher sensitivities for prompt-gamma
      activation analysis (PGAA), and thus to new applications for this technique. For
      analytical accuracy, the details of neutron scattering within the sample need to
      be taken into account; this consideration is especially important for most
      materials of biological origin.

PMID- 7710863
TI  - A comparative study of elemental composition of human breast milk and infant milk
      substitutes.
AB  - Instrumental neutron activation analysis (INAA) and proton-induced X-ray emission
      (PIXE) analysis have been employed to determine the concentration of 13 elements
      in human breast milk, various infant formulas, and locally produced cereals from
      Nigeria, as well as from various infant formulas and natural cow and goat milk
      available in the UK. The study shows that if the locally produced cereal is to be
      used on a regular basis for babies in Nigeria, then their diet must be
      supplemented with essential trace elements. Furthermore, parents should be
      discouraged from giving their infants cow and goat milk because of the high
      concentration of major elements compared to human breast milk.

PMID- 7710864
TI  - Trace element contents in food determined by neutron activation analysis and
      other techniques.
AB  - Advances in analytical methodology and sophisticated instrumentation introduced
      during the last few decades have not only helped to recognize the presence of a
      large number of essential and toxic trace elements in biological materials and
      food stuffs, but also added a new dimension in our understanding of their role in
      health and disease. In deficiency states, most essential trace elements cause
      health problems. The trace element problem as a public health issue has a very
      low priority in developing countries. Daily dietary intake data based on well
      conducted studies are limited in many parts of the world. The present authors are
      in the process of generating data for the intake levels of a number of major and
      minor inorganic elements both in developed and developing countries. The results
      so far obtained show wide variations. The intake levels of several elements,
      including potassium, magnesium, zinc, copper, and selenium, are below the current
      recommended levels. The concentration of toxic metals, such as aluminum, cadmium,
      lead, and mercury, are within acceptable limits in most of the diets analyzed.

PMID- 7710865
TI  - Determination of trace elements in human lung samples.
AB  - Lung samples from smokers, nonsmokers, and one stillborn were analyzed by an
      instrumental neutron activation analysis (INAA) method. Pulmonary tissue and
      hilum lymph node samples were obtained separately from autopsies, and then
      submitted to cryogenic homogenization, lyophilization, and sterilization. Short
      and long irradiations were performed in an IEA-R1 nuclear reactor, and gamma-ray
      activities were measured using a Ge(Li) or hyperpure Ge detector. Precision of
      results was evaluated by analyzing one lung tissue in replicates and their
      accuracy by analyzing reference materials. Comparisons were carried out between
      results obtained in pulmonary tissues and lymph nodes, as well as those obtained
      in samples from different groups of individuals.

PMID- 7710866
TI  - Levels of some trace elements in serum of Prague inhabitants measured by INAA.
AB  - Sera of 240 randomly selected Prague inhabitants of both sexes from ages 6 to 65
      yr were analyzed by instrumental neutron activation analysis (INAA) for Fe, Zn,
      Se, Rb, Cs, and Sc. Significant differences were found between serum Fe and Zn
      levels of men from Prague and from rural regions of Central Bohemia.
      Concentration of Se was one of the lowest in Europe and exhibited age-dependent,
      but not sex-dependent changes. Age-dependent changes of serum concentrations were
      also found for Rb, Cs, and Sc, whereas sex-dependent changes were detected for
      Zn, Rb, Cs, and Sc.

PMID- 7710867
TI  - Determination of aluminum and phosphorus in biological materials by reactor
      activation analysis using germanium as integral flux monitor and comparator.
AB  - A method for determination of aluminum and phosphorus in biological materials,
      based on activation in a nuclear reactor and measurement of 28Al, produced by the
      27Al(n, gamma)28Al and 31P(n, alpha)28Al reactions, is described. Irradiations in
      the undisturbed and epicadmium spectra provide a two-equation system in order to
      determine the contributions of aluminum and phosphorus to the total activities.
      Germanium is used as an integral flux monitor and comparator, through the
      reactions: 74Ge(n, gamma)75Ge, 76Ge(n, gamma)77Ge, and 72Ge(n,p)72Ga.

PMID- 7710868
TI  - Effect of enhanced bromide intake on the concentration ratio I/Br in the rat
      thyroid gland.
AB  - Interaction of bromine with iodine was studied in the rat thyroid gland under the
      conditions of different bromide intake. Bromine and iodine in the thyroid dry
      weight were determined by instrumental neutron activation analysis (INAA). It was
      found that with increased bromide intake the bromine concentration in the thyroid
      gland increased with simultaneous decrease in the iodine concentration. The
      change in the I/Br concentration ratio depends on a number of halogen binding
      positions and on the bromide supply. The I/Br parameter reacts sensitively to the
      changes of bromide intake already in the region of low bromine concentration
      levels.

PMID- 7710869
TI  - Neutron activation analysis of biological samples at the radiochemistry division
      of IPEN-CNEN/SP.
AB  - Neutron activation analysis is a very useful method for determination of a great
      number of elements in biological samples. At the Radiochemistry Division of the
      IPEN-CNEN/SP, this method is being extensively applied to study several
      materials, such as extracts from medicinal plants, human hair, snake venoms,
      human lungs, food-stuffs, and corn samples. Both instrumental neutron activation
      analysis (INAA) and radiochemical neutron activation analysis (RNAA) are used to
      analyze real samples, as well as biological standard reference materials to
      evaluate the accuracy and precision of the results.

PMID- 7710870
TI  - Some improvements in the quality of NAA procedures and the reliability of the
      results.
AB  - After considering the need for quality control in NAA, the concept of quality in
      NAA procedures themselves is discussed, and some important factors identified.
      Two approaches to improve quality are then described in more detail. The first
      concerns the unique ability of NAA using different isotopic reactions and
      different modes (INAA/RNAA) to provide independent data sets in the same
      laboratory, thus allowing internal validation or crosschecking. The second
      discusses the need for chemical yield measurements in RNAA and the advantages of
      the radioisotopic tracer technique. Some recent advances and further
      possibilities for this use of tracers are listed.

PMID- 7710871
TI  - RNAA as compared to ICP-MS for the analysis of normal human serum.
AB  - The merits of radiochemical neutron activation analysis (RNAA) and inductively
      coupled plasma mass spectrometry (ICP-MS) are critically discussed for the
      determination of trace and ultratrace elements in normal human serum. For RNAA,
      two semiautomated procedures, allowing the determination of up to 18 elements,
      are briefly described. ICP-MS has a series of interesting features for the
      determination of trace elements. Matrix and spectral interferences can mostly be
      avoided or corrected for. After a simple 5- or 10-fold dilution and addition of
      an internal standard, more than 20 elements can be measured precisely and
      accurately.

PMID- 7710872
TI  - Intercomparison of techniques available at INETI in the analysis of two IAEA
      candidate research materials.
AB  - Under contract with the IAEA, the epiphytic lichen Evernia prunastri was
      collected to prepare a multielement lichen reference material for quality
      assurance of environmental studies. An intercomparison run on trace and minor
      elements in this candidate research material (IAEA-336) was organized in which
      six analytical groups of the National Institute of Engineering and Industrial
      Technology (INETI) took part. INAA, PIXE, XRF, AAS, and ICP-ES were applied. The
      results obtained by different methods are compared, and their complementarity is
      discussed. As a quality control, the IAEA cabbage research material (IAEA-359)
      was analyzed. The results agree quite well with the estimated values given by the
      IAEA.

PMID- 7710873
TI  - Developments in tomographic methods for biological trace element research.
AB  - Neutron-induced gamma-ray emission tomography for quantitative determination of
      concentration and distribution of elements in a selected plane through a
      biological specimen is briefly explained and applied by way of illustration to
      the analysis of gallstones. A system capable of carrying out studies of the
      binding site of 75Se is different matrices using time differential perturbed
      angular correlation spectroscopy is also briefly described. Developments in the
      detector technology of positron emission tomography have allowed small-diameter
      imaging devices to be built for in vivo preclinical evaluation of new tracers in
      small animals and are discussed in the context of a proposed experiment combining
      the techniques mentioned above.

PMID- 7710874
TI  - Comparative study of methods for determining lanthanide elements in biological
      materials by using NAA, HPLC postcolumn reaction, and ICP-MS.
AB  - Mice were injected intravenously with one of the following elements: Y, La, Ce,
      Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, or Yb, at a dose of 25 mg/kg body wt. After 20 h,
      the various organs were taken out, and the element concentrations were determined
      by NAA, HPLC postcolumn reaction, or ICP-MS. The results by these three methods
      were within the acceptable range. About 85% of the amount administered of each
      element was found in liver, lung, and spleen.

PMID- 7710875
TI  - The IRMM--International Measurement Evaluation Program (IMEP). IMEP-3--trace
      elements in synthetic and natural water.
AB  - The aim of the IRMM--International Measurement Evaluation Program (IMEP) is to
      test out a possible realization of international measurement comparability for
      field laboratories through traceability of their measurements to the SI Unit for
      amount of substance: the mole. In IMEP-3, 10 different trace elements, B, Ca, Cd,
      Cu, Fe, K, Li, Pb, Rb, and Zn, were determined in a synthetic and a natural water
      by participating laboratories using their routine methods and graphically
      compared (in coded form) to certified values, established by IRMM and NIST using
      an isotope-specific method (Isotope Dilution Mass Spectrometry, Neutron
      Activation Analysis). The number of participants was 70; 64 laboratories have
      reported results. The results show a spread of more than 50% asymmetrically
      around the certified value. The Youden graphs allow evaluation of the overall
      performance of the laboratories in the IMEP-3 round.

PMID- 7710876
TI  - Validation of the cumulative or replicate NAA method for the determination of
      trace elements in biological materials.
AB  - To make the best use of time and facilities, a neutron activation system, fully
      automatic, including spectrum and data processing, to be used with short-lived
      nuclides, has been recently developed at the Portuguese Research Reactor (in
      Portuguese "Reactor Portuges de Investigacao," RPI). Using this system, the
      cumulative neutron activation analysis method is now being implemented. This
      article summarizes the experimental procedures used to validate the cumulative
      NAA method for the determination of selenium in biological samples, emphasizing
      the determination of the essential characteristics of precision, accuracy, and
      limits of detection and of quantification of the method. The article also
      examines how detection limits and precision are improved when the samples are
      analyzed by this method compared to the cyclic activation measurements in use at
      RPI for the determination of selenium. The improvement is demonstrated for the
      measurement of selenium in several reference materials when the result obtained
      by adding up seven spectra of separate aliquots of the same sample is compared to
      the result from a cumulative spectrum of seven (whenever possible) consecutive
      cycles of a single sample.

PMID- 7710877
TI  - Sum and mean. Standard programs for activation analysis.
AB  - Two computer programs in use for over a decade in the Nuclear Methods Group at
      NIST illustrate the utility of standard software: programs widely available and
      widely used, in which (ideally) well-tested public algorithms produce results
      that are well understood, and thereby capable of comparison, within the community
      of users. Sum interactively computes the position, net area, and uncertainty of
      the area of spectral peaks, and can give better results than automatic peak
      search programs when peaks are very small, very large, or unusually shaped. Mean
      combines unequal measurements of a single quantity, tests for consistency, and
      obtains the weighted mean and six measures of its uncertainty.

PMID- 7710878
TI  - A PC-based computer program for quality assessment of INAA results of emission
      and air particulate samples.
AB  - A PC-based computer program for quality assessment (QAS) of results obtained by
      neutron activation analysis (NAA) is described. Program QAS is designed for the
      quality assurance system based on a routine use of certified reference materials
      (CRMs) with similar matrix composition as the samples analyzed together with each
      sample batch. The results obtained for CRMs samples are then compared with
      certified (true) values and with the results obtained for particular CRM in
      previous analysis runs. Five various tests are applied to check the quality of
      NAA results (for CRM and, consequently, for real samples) obtained for a
      particular analysis run. Control charts for elemental concentrations found in CRM
      and ranges of results for duplicate aliquots of CRM are displayed to visualize
      possible discrepancies. The program accepts files transported from gamma-ray
      spectrometric system ND 683 (based on a PDP 11 computer), extracts and stores
      reference material results, and prepares a work spreadsheet for each set of
      results to avoid typist and other kinds of errors.

PMID- 7710879
TI  - Accurate determination of cobalt traces in several biological reference
      materials.
AB  - A newly devised, very accurate ("definitive") method for the determination of
      trace amounts of cobalt in biological materials was validated by the analysis of
      several certified reference materials. The method is based on a combination of
      neutron activation and selective and quantitative postirradiation isolation of
      radiocobalt from practically all other radionuclides by ion-exchange and
      extraction chromatography followed by gamma-ray spectrometric measurement. The
      significance of criteria that should be fulfilled in order to accept a given
      result as obtained by the "definitive method" is emphasized. In view of the
      demonstrated very good accuracy of the method, it is suggested that our values
      for cobalt content in those reference materials in which it was originally not
      certified (SRM 1570 spinach, SRM 1571 orchard leaves, SRM 1577 bovine liver, and
      Czechoslovak bovine liver 12-02-01) might be used as provisional certified
      values.

PMID- 7710880
TI  - NAA methodology for the certification of eight trace elements in a plankton
      reference material.
AB  - Neutron activation analysis (NAA) methodology was applied for the certification
      of eight trace elements (As, Co, Cr, Cu, Hg, Mn, Se, and Zn) in a plankton
      reference material (CRM 414) prepared by the BCR of the Commission of the
      European Communities. Average concentrations (micrograms/g dry wt) and standard
      deviations found in plankton for the eight trace elements were as follows: As
      6.29 +/- 0.19, Co 1.37 +/- 0.05, Cr 23.7 +/- 0.56, Cu 27.1 +/- 0.88, Hg 0.29 +/-
      0.02, Mn 285 +/- 4.1, Se 1.62 +/- 0.10, and Zn 114 +/- 3.4. All values found were
      to be in very good agreement (0.5%-8.1%) with certified values.

PMID- 7710881
TI  - Interlaboratory analysis of IRM NSC-21 Compost Vitahum.
AB  - The preparation of internal reference material NSC-21 Compost Vitahum, including
      its stabilization, homogeneity testing, and evaluation of an interlaboratory
      comparison in which 19 laboratories took part using several analytical methods is
      described. From the results of the intercomparison, consensus values were derived
      for the contents of Cd, Cu, Ni, Pb, and Zn, whereas for As, Co, Cr, Fe, Hg and
      Mn, information values were derived. Bimodal distribution of the As and Cr
      results was obtained, presumably because of incomplete dissolution of the
      elements from the matrix if insufficiently aggressive decomposition procedures
      were employed. Some problems encountered were elucidated by application of
      neutron activation analysis (NAA) in its nondestructive and destructive
      (radiochemical) modes.

PMID- 7710882
TI  - Nuclear and conventional methods for soil determination in sugar cane industry.
      Validity of sampling procedure.
AB  - Scandium and ash methods' performances were compared in terms of soil content
      assessment in sugar cane loads, emphasizing the common sampling drawbacks. Both
      methods are adequate for such determination in controlled conditions. The
      scandium has demonstrated better analytical characteristics, since it is free
      from interferences of cane matrix, which decreases the accuracy of the ash method
      in normal mill conditions.

PMID- 7710883
TI  - Use of total reflection X-ray fluorescence analysis in the life sciences.
AB  - Total Reflection X-ray Fluorescence Analysis (TXRF) is accepted as a powerful
      analytical tool. TXRF is basically an energy-dispersive technique with the sample
      excitated in total reflection geometry. Simultaneous detection of almost all
      chemical elements and lower limits of detection for medium Z elements in the
      range of a few hundred fg are achievable at optimized excitation conditions.
      Aqueous and acidic solutions are the preferred sample types, so a lot of
      applications in the life sciences are given. For solids and other samples,
      special preparation techniques are required.

PMID- 7710884
TI  - Programs of the IAEA utilizing nuclear analytical techniques in the life
      sciences.
AB  - Nuclear analytical techniques have an important role in the IAEA in life sciences
      programs relating to human health. A major effort has recently been devoted to
      the determination of dietary intakes of trace elements, including studies in some
      countries affected by the Chernobyl accident. The same accident stimulated
      interest in using 129I (as determined by NAA and other techniques) to trace the
      distribution of fission products in the environment. Other research topics
      concern solid wastes, air pollution, exposure to mercury in selected human
      populations, and osteoporosis (including NAA studies of trace elements in human
      bone). Much of the IAEA's work is concerned with analytical quality control; new
      reference materials in preparation include lichen (for trace elements) and human
      hair (for total and methyl mercury).

PMID- 7710885
TI  - Evaluation of the washing system efficiency in sugar cane mills by neutron
      activation analysis.
AB  - The effectiveness of industrial washing operation in minimizing soil in sugar
      cane delivered to mills is evaluated. Instrumental neutron activation analysis
      was the nuclear analytical technique chosen for this work, with Fe, Hf, Sc, and
      Th selected as soil tracers. On the basis of differences between elemental
      concentration of integral and prepared cane, that is before and after washing,
      the feasibility of the method for evaluation of the washing efficiency is
      demonstrated.

PMID- 7710886
TI  - Determination of copper by isotopic dilution.
AB  - A rapid and selective method was used for the determination of copper by isotopic
      dilution employing substoichiometric extraction with dithizone in carbon
      tetrachloride. The appropriate pH range for the substoichiometric extraction was
      2-7. In the analysis, even a large excess of elements forming extractable
      complexes with dithizone does not interfere. The accuracy and precision of the
      method were evaluated. The method has been applied to analysis of reference
      materials, wheat flour, wine, and beer.

PMID- 7710887
TI  - Simulation and optimization of cyclic activation analysis of short-lived isotopes
      with 14MeV neutron generator.
AB  - A program of simulation and optimization is developed for the case of cyclic
      activation analysis of short-lived isotopes with 14-MeV neutrons. The background
      line under the photopeaks of interest is simulated using Zikovsky's model. The
      reliability of the program is checked on real conditions with a geological
      reference sample "Soil 5" provided by the IAEA. Optimum experimental conditions
      (timing parameters, number of cycles) are determined, and corresponding detection
      limits calculated. A systematic study of short-lived isotopes with half-lives
      lower than 5 min is done for Soil 5, and the results are discussed.

PMID- 7710888
TI  - Measurement of uranium content and its distribution in some crustacea of
      Mysidacea species by the fission track method.
AB  - Uranium distributions and contents in Mysidacea species were investigated in
      order to be subsequently correlated with some specific properties of these
      crustacea. The fission track micromapping technique was used in uranium
      distribution and content measurements. The investigated biological samples were:
      (1) Javanisomysis gutzui Bacescu, 1992 and (2) Mesopodopsis slabberi Van Beneden,
      1861. The determined contents varied in the range of natural background values of
      uranium.

PMID- 7710889
TI  - True-coincidence correction when using an LEPD for the determination of the
      lanthanides in the environment via k0-based INAA.
AB  - As part of a recent study on the environmental effects caused by the operation of
      a coal-fired power station at Sines, Portugal, k0-based instrumental neutron
      activation analysis (INAA) was used for the determination of the lanthanides (and
      also of tantalum and uranium) in plant leaves and lichens. In view of the
      accuracy and sensitivity of the determinations, it was advantageous to make use
      of a low-energy photon detector (LEPD). To begin with, in the present article, a
      survey is given of the former developments leading to user-friendly procedures
      for detection efficiency calibration of the LEPD and for correction for true
      coincidence (cascade summing) effects. As a continuation of this, computer
      coincidence correction factors are now tabulated for the relevant low-energetic
      gamma-rays of the analytically interesting lanthanide, tantalum, and uranium
      radionuclides. Also the 140.5-keV line of 99Mo/99mTc is included, molybdenum
      being the comparator chosen when counting using an LEPD.

PMID- 7710890
TI  - The influence of scattering on the total efficiency for point sources in gamma
      ray spectrometry.
AB  - The contribution of gamma-ray scattering to the total efficiency for point-source
      geometries in a gamma spectrometer was measured. Scattering of gamma-rays on the
      shield and in the sample was considered. For a 25% efficiency detector in a small
      shield, about a 1% contribution to the total efficiency was measured, whereas for
      samples of a few hundred grams, these contributions reached 1-2%. Simple models
      for description of the effects are presented.

PMID- 7710891
TI  - Distribution of Na, K, Rb, Cs, and 137Cs in some Austrian higher fungi.
AB  - The level of 137Cs in 28 species of mushroom collected and analyzed between 1986
      and 1992, after the Chernobyl accident, are reported. Xerocomus badius was found
      to accumulate 137Cs (the median value of 58 samples is 3667 Bq/kg). The 137Cs
      content of Rozites caperata, Scleroderma vulgare, and Tylopilus felleus exceeded
      600 Bq/kg. Some of these samples collected in August 1992 were investigated for
      their 134Cs and 137Cs content as well as their Na, K, Rb, and Cs levels by
      applying instrumental neutron activation analysis (INAA). The results show a high
      correlation coefficient (0.80) between the contents of 137Cs and Na, but none
      between 137Cs and K.

PMID- 7710892
TI  - Radioactive contamination of forests in Poland.
AB  - Partial results of a large survey of radioactive contamination in Polish forests
      are presented. All measurements were performed with low-background gamma
      spectrometers. The measurement method is briefly described. Activities of 137Cs,
      134Cs, 125Sb, 106Ru, 144Ce, 154Eu, 155Eu, and 60Co in A0 and A1 layers of forest
      litter from all over Poland are determined. The geographical distribution of
      contamination as well as its origin is discussed. Nonuniform composition of the
      Chernobyl fallout over Poland is confirmed and documented.

PMID- 7710893
TI  - The measurement of low concentrations of Kr-85 in atmospheric air samples.
AB  - Krypton-85 atmospheric contamination produced by the nuclear industry has been
      investigated on the basis of regular measurements. 85Kr concentrations observed
      in ground-level air of Prague between 1983 and 1993 are presented and their time
      related changes analyzed. The long-term trend of 85Kr activity increased steadily
      over the monitored period with the growth rate of 38 mBq.m-3 (STP)/yr and reached
      about 1.2 Bq.m-3 (STP) in 1992. Short-term variations of the baseline level with
      the average amplitude of 12% show a seasonal periodicity. Occasionally detected
      extreme values of up to 2.5 Bq.m-3 (STP) indicate undispersed emissions from
      distant nuclear fuel reprocessing plants.

PMID- 7710894
TI  - Applications of PIXE in the life sciences.
AB  - During the last decade, particle-induced X-ray emission spectrometry (PIXE) has
      been accepted by the analytical chemistry community as a standard method. Instead
      of routine bulk analysis of biomedical samples where several competing analytical
      techniques are available, the full strength of PIXE could be exploited in special
      applications where also location of the detected ions is desirable. In this
      article, two different approaches for this purpose are discussed and illustrated:
      (1) nuclear microscopy, where micro-PIXE utilizing a proton beam spot of approx 1
      micron 2 or less promises unique perspectives to obtain elemental maps at the
      cellular level, and (2) in situ PIXE analysis of the minute metalloprotein
      volumes concentrated in thin-layer electrophoretograms.

PMID- 7710895
TI  - Extraction of uranium from acidic solutions by TBP impregnated polyurethane foam.
AB  - Polyurethane foams can be used as a selective absorbent for a number of
      substances from dilute aqueous solutions. Absorption of uranium (VI) has been
      investigated using an open-cell polyurethane foam impregnated with tri-butyl
      phosphate (TBP). The extraction efficiency was observed to depend on the pH of
      the uranium solution and the concentration of uranyl ions. Also, the effects of
      TBP concentration, temperature, and squeezing time on the extraction of uranium
      were examined.

PMID- 7710896
TI  - Investigation of uranium recovery from dilute aqueous solutions using silk
      fibroin.
AB  - The uranium uptake ability of silk fibroin was investigated. High ability to
      uptake uranium from nonsaline water containing 2.500 mg of uranium was observed
      with the silk fibroin tested. The uranium uptake was very rapid and was dependent
      on pH, uranium concentration, temperature, and retention time. Almost all uranium
      taken up is easily eluted with 1 mol/L CH3COONH4. This biomatrix, therefore,
      appears to have potential for use in a commercial process for uranium recovery
      from uranium-containing waste water.

PMID- 7710897
TI  - Radiotracer method in the study of environmental speciation and migration of
      contaminants.
AB  - Principles, advantages, and limitations of the use of radiotracer method for the
      analysis of speciation and migration of contaminants in the environment are
      briefly discussed. Several recent examples of use in the author's laboratory are
      given: development of the separation method for methylmercury and inorganic
      mercury in hair, analysis of the speciation of cadmium in soil solutions, study
      of the interaction of 137Cs and 58Co with suspended sediments in river water, and
      determination of input data for mathematical modeling of radiocesium migration in
      a small river.

PMID- 7710898
TI  - Comprehensive RNAA of cadmium, cobalt, nickel, and copper using 109Cd, 57Co, and
      reactor-produced 67Cu as radioisotopic yield monitors.
AB  - An existing radiochemical NAA procedure for Cd, Co, and Cu was improved to allow
      determination of individual radiochemical yields by the radioisotopic tracer
      technique, thus eliminating errors owing to variable recovery. 109Cd was used as
      tracer for Cd determination via 115Cd/115mIn, 57Co for Co via 60Co, and
      potentially for Ni via 58Co, whereas as a novelty 67Cu, produced by reactor
      irradiation of ZnO of natural isotopic composition (by the 67Zn [n,p] 67Cu
      reaction) was used for Cu via the indicator nuclide 64Cu. The simple production
      and purification of 67Cu by anion exchange is described. Results for biological
      RMs are given and discussed.

PMID- 7710899
TI  - Nuclear analytical methods in the life sciences.
AB  - A survey is given of various nuclear analytical methods. The type of analytical
      information obtainable and advantageous features for application in the life
      sciences are briefly indicated. These features are: physically different basis of
      the analytical method, isotopic rather than elemental determination, no
      interfering effect of electrons and molecular structure, and penetrating
      character of nuclear radiation. Suggestions are given for exploitation of the
      sometimes unique potentials of nuclear analytical methods, particularly when
      requiring considerable investment for equipment, supporting facilities, and
      specialized staff.

PMID- 7710900
TI  - Enhanced sensitivity for the determination of selenium by INAA.
AB  - A working analytical procedure for selenium determinations by INAA, using gamma
      spectrometry with a germanium well-type detector, is presented. The spectral line
      at 400.7 keV is employed, enhanced with the effect of energy summing in true
      coincidence of cascade photons. The main advantage of the method is high
      efficiency and reliable, interference-free results; potential drawbacks are
      increases in input count rate and pile-up losses, decrease in resolution, and
      sensitivity to errors in sample-to-detector geometry. The procedure is applied to
      certification analysis of reference materials, large-area biomonitoring by oak
      leave samples, and determination of separated proteins.

PMID- 7710901
TI  - Genetics of drug resistance.

PMID- 7710902
TI  - In vivo models of P-glycoprotein-mediated multidrug resistance.

PMID- 7710903
TI  - Molecular diagnosis of multidrug resistance.

PMID- 7710904
TI  - Clinical reversal of multidrug resistance.

PMID- 7710905
TI  - Role of gene amplification in drug resistance.

PMID- 7710906
TI  - Mechanisms of acquired resistance to cisplatin.

PMID- 7710907
TI  - Mechanisms of resistance to alkylating agents.

PMID- 7710908
TI  - Mechanisms of resistance to topoisomerase inhibitors.

PMID- 7710909
TI  - The role of protein kinase C in multidrug resistance.

PMID- 7710910
TI  - Transcriptional regulation of multidrug resistance gene expression.

PMID- 7710911
TI  - In vitro models of multiple drug resistance.

PMID- 7710912
TI  - Biological preservation of foods with reference to protective cultures,
      bacteriocins and food-grade enzymes.
AB  - A review is presented on the present status of biological preservation of foods.
      Recent developments are discussed with respect to underlying mechanisms of
      inhibition by 'protective' cultures, and special reference is made to lactic acid
      bacteria (LAB) and their 'food-grade' safety. The role of bacteriocins, their
      limitations and potentiating role in biological systems, is also addressed. The
      use of enzymes (e.g. lysozyme) for food preservation is mainly restricted by
      economic factors, their inactivation by endogenous food components and their
      limited activity spectrum. Practical applications of protective cultures refer to
      particular food commodities that either constitute novel systems with respect to
      packaging and/or composition, or represent special hygienic risks. It is
      concluded that biological preservation cannot substitute GMP; it, however, offers
      an additional (and acceptable) processing parameter for improving the safety and
      assuring the quality of a given food.

PMID- 7710913
TI  - Numerical taxonomy of an 'atypical' population of gram-positive cocci isolated
      from freshly dressed lamb carcasses.
AB  - One hundred Gram-positive, catalase-positive strains were isolated from freshly
      dressed lamb carcasses. They were randomly selected from a non-selective medium
      and tested for 75 characters. Only nine cultures could be identified by
      conventional methods. A numerical taxonomic study was conducted on the whole
      population and 25 reference strains. At the 80% similarity level (Ssm), ten
      clusters were formed. Five of them were entirely composed of reference strains.
      Phena V and VIII contained seven isolates and two reference strains of
      Micrococcus. Phena VI (six unidentified isolates), VII (nine staphylococci) and
      IX (69 unidentified isolates) were more related to M. kristinae than to the
      remaining reference strains. Properties with possible implications in meat
      spoilage were: strong lipolytic activity (76%), anaerobic growth (85%), tolerance
      to 15% (w/v) NaCl (95%) and ability to grow at 15 degrees C (95%) and 4 degrees C
      (26%).

PMID- 7710914
TI  - Comparison of seven selective media for the isolation of mesophilic Aeromonas
      species in fish and meat.
AB  - Seven selective agar media and two enrichment broths were evaluated for their
      suitability for the isolation of mesophilic Aeromonas species from meat, fish,
      and shellfish samples. In a first trial, aeromonads were inoculated in fish and
      meat samples and reisolated using all selected media. For qualitative isolation,
      enrichment in alkaline peptone water (pH 8.7 +/- 0.1) at 28 degrees C and
      subsequent plating onto sheep blood agar supplemented with 30 mg/L ampicillin
      (ASBA 30) and bile salts-irgasan-brilliant green agar (BIBG) at 35 degrees C led
      to the best results. For quantitative assays, direct plating on the same agar
      media is recommended. In a second trial, 829 meat, fish, and shellfish samples
      were investigated with the same methods. The results show that BIBG is the most
      selective medium and that presumptive identification of aeromonads on ASBA 30 is
      very easy. Finally, we could confirm the opinion of other workers that optimal
      recovery of mesophilic Aeromonas spp. requires the use of more than one agar
      medium.

PMID- 7710915
TI  - Growth and penetration of Salmonella enteritidis, Salmonella heidelberg and
      Salmonella typhimurium in eggs.
AB  - Eggs and egg dishes are important vehicles for Salmonella infections. Salmonella
      enteritidis, Salmonella typhimurium and Salmonella heidelberg, which can be
      isolated from chicken ovaries and feces, have been implicated in approximately
      50% of the foodborne salmonellosis outbreaks in the United States. In this study,
      the growth of these three organisms, inoculated into yolks and albumen, was
      compared at 4, 10 and 25 degrees C. Regardless of whether 10(2) cfu/g or 10(4)
      cfu/g was inoculated into the yolk or albumen, populations of all strains
      increased 3 logs or more in number in one day when incubated at 25 degrees C.
      Maximum numbers of Salmonella ranged from 10(8) to 10(10) cfu/g. All strains grew
      at 10 degrees C, but peak numbers were lower and occurred later than those at 25
      degrees C. Populations of the three Salmonella strains inoculated into eggs
      stored at 4 degrees C grew sporadically; in some test groups populations
      declined. The potential for Salmonella in contaminated feces to establish in the
      interior of eggs was examined by monitoring shell penetration. At 25 degrees C,
      all three Salmonella strains penetrated the shell in 3 days, but at 4 degrees C,
      only S. typhimurium was found in one membrane sample. When hatchery conditions
      were simulated by incubating eggs at 35 degrees C for 30 min followed by storage
      at 4 degrees C, penetration was enhanced. Penetration was observed by day 1-3
      when eggs were exposed to 10(4) cfu Salmonella/g feces. Increasing the inoculum
      to 10(6) cfu/g feces resulted in 50-75% of the contents of eggs to be
      contaminated by day 1. All Salmonella-positive samples were detected by
      enrichment. Results of this study indicate that S. enteritidis, S. typhimurium,
      or S. heidelberg present in feces can penetrate to the interior of eggs and grow
      during storage.

PMID- 7710916
TI  - Rapid and economical detection of Salmonella enteritidis in eggs by the polymyxin
      cloth enzyme immunoassay.
AB  - A rapid, simple and economical procedure for the detection of Salmonella
      enteritidis in eggs was developed. The contents of whole eggs inoculated with low
      numbers of S. enteritidis were mixed with a minimal volume of a nutrient-rich
      broth (1:2 ratio of egg to broth) and incubated overnight. The lipopolysaccharide
      (LPS) antigens of S. enteritidis were extracted by heating in the presence of
      cholate. The antigens were captured on polymyxin-coated polyester cloth, and the
      captured antigens were detected by sequential reactions with anti-serogroup D1
      rabbit antiserum, anti-rabbit antibody-peroxidase conjugate and
      tetramethylbenzidine substrate solution. This polymyxin-cloth enzyme immunoassay
      (polymyxin-CEIA) was highly specific for salmonellae bearing the factor O:9
      antigen, reacting in the assay of 19 S. enteritidis strains tested, including two
      rough isolates, but not with salmonellae lacking the factor O:9 antigen or non
      Salmonella bacteria. The threshold sensitivity of the polymyxin-CEIA for S.
      enteritidis suspensions was ca. 10(6) cfu/ml. This combined enrichment culture
      and polymyxin-CEIA required less than 24 h to complete and detected as few as 1-2
      S. enteritidis cfu inoculated into a whole egg. This procedure should facilitate
      the routine monitoring of S. enteritidis in large numbers of egg samples.

PMID- 7710917
TI  - Microbial degradation of amygdalin of bitter apricot seeds (Prunus armeniaca).
AB  - Amygdalin is a cyanogenic glycoside occurring among others in almonds and bitter
      apricot seeds with interesting levels of dietary protein. Utilization of seeds
      for human or animal nutrition requires adequate detoxification. In the present
      paper, selected filamentous fungi (Mucor circinelloides, Penicillium nalgiovense)
      and yeasts (Hanseniaspora valbyensis, Endomyces fibuliger) were tested for their
      in-situ ability to decompose amygdalin. The latter (Endomyces fibuliger) was best
      able to grow on autoclaved bitter apricot seeds and detoxify them from 30
      microMol CN/g dry matter to less than 1 microMol CN/g dry matter after 48 h of
      incubation at 27 degrees C.

PMID- 7710918
TI  - Mycotoxin production by Alternaria alternata strains isolated from red delicious
      apples in Argentina.
AB  - Eleven Alternaria alternata strains isolated from Red Delicious apples in cold
      storage in Argentina, were tested for alternariol and alternariol methyl ether
      production in laboratory media and in whole fresh fruits. Most of them were able
      to produce both toxins in all media. They were detected also in mycelium free
      filtrates from liquid cultures and in asymptomatic tissues from inoculated fruit.
      Thus, in the evaluation of mouldy core incidence in apples, the presence of A.
      alternata toxins in tissues should be considered even in the absence of mycelia.

PMID- 7710919
TI  - Characterization of Yersinia enterocolitica isolated from the oral cavity of
      swine in Slovakia.
AB  - Yersinia enterocolitica was detected in 160 of 2760 examined samples that were
      prepared from dental cavity of 920 pigs. From the isolates 49 strains were
      characterized with respect to their genetic and phenotypic markers of virulence.
      All strains were belonging to serogroup 0:3, biovar 4. Forty-one isolates (84%)
      harboured the virulence plasmid detected by DNA colony hybridization. Of the
      other assays of virulence--autoagglutination, binding of crystal violet,
      pyrazinamidase activity, calcium dependence and Congo red binding--the latter two
      exhibited the best correlation with the detected presence of plasmid DNA.

PMID- 7710920
TI  - Subunit- and brain region-specific reduction of GABAA receptor subunit mRNAs
      during chronic treatment of rats with diazepam.
AB  - The mRNA levels for several GABAA receptor subunits were measured by Northern
      blot analysis. Rats were treated for 3 wk by continuous release of diazepam (DZP)
      from subcutaneous reservoirs, and then sacrificed immediately or 48 h after
      removing the reservoirs. Poly(A)+ RNAs, isolated from cerebral cortex,
      cerebellum, and hippocampus, were hybridized with oligonucleotide probes for
      GABAA receptor subunits and a cDNA probe for beta-actin. Subunit mRNAs were
      expressed relative to the corresponding beta-actin mRNA. DZP treatment decreased
      the alpha 1 subunit mRNA level 40% in hippocampus, but it was not changed in
      cortex or cerebellum. The alpha 5 subunit mRNA level was decreased in cerebral
      cortex (28%) and hippocampus (15%). The gamma 2 subunit mRNA level was decreased
      (40%) only in cortex. DZP treatment did not affect alpha 2, alpha 3, alpha 4,
      beta 2, or beta 3 subunit mRNA levels. Decreases in mRNA levels had reversed
      within 48 h after stopping chronic treatment. Acute DZP did not change alpha 1,
      alpha 5, or gamma 2 subunit mRNA levels. The decreases in GABAA receptor subunit
      mRNA levels were specific to subunit and brain region. These results, coupled
      with those after chronic flurazepam treatment, also indicated that the effects on
      GABAA receptor subunit mRNA levels are specific to the benzodiazepine (BZ) used
      for chronic treatment.

PMID- 7710921
TI  - Increased globotriaosylceramide on plasma membranes of synchronized familial
      dysautonomia cells. Verotoxin binding studies.
AB  - Familial dysautonomia is an autosomal recessive genetic disease found almost
      exclusively among Ashkenazi Jews, characterized by deficits in autonomic,
      sensory, and central functions. Although the gene has been localized to
      chromosome 9, the biochemical defect remains elusive. We previously reported an
      increase in globotriaosylceramide in dysautonomic fibroblasts and lymphoblasts,
      and unusual fibroblast growth patterns suggesting plasma membrane abnormalities.
      Globotriaosylceramide is a plasma membrane component, and the natural receptor
      for verotoxin derived from E. coli. In Vero and HeLa cells, which are susceptible
      to verotoxin, the expression of globotriaosylceramide on the cell surface is
      maximal at the G1/S boundary of the cell cycle. Measurement of toxin binding at 0
      degrees C at this boundary is indicative of the amount of globotriaosylceramide
      exposed on the cell surface. Above 0 degrees C, verotoxin enters, and is toxic
      to, the cell. We analyzed verotoxin-globotriaosylceramide interactions in
      synchronized FD and normal cells at this boundary. 125I-toxin binding was much
      more marked to lymphoblasts from patients than from controls. When cells were
      grown in the presence of verotoxin, at 10(-2)-10(-7) micrograms/mL, 70% of
      dysautonomic lymphoblasts died, compared to 25% of controls. The CD50 was 10
      ng/mL for dysautonomic fibroblasts vs 450 for controls. These results may be
      exploited to create a biological assay to differentiate between FD and normal
      cells.

PMID- 7710922
TI  - Dichloroacetate attenuates neuronal damage in a gerbil model of brain ischemia.
AB  - Dichloroacetate facilitated a reduction in brain lactate following ischemia in
      the gerbil. This treatment also improved high-energy metabolite and pyruvate
      dehydrogenase enzyme recovery. The purpose of this study was to determine the
      effect of dichloroacetate on ischemia-induced neuronal damage in the hippocampus
      of the gerbil. In adult male gerbils, carotid arteries were clamped bilaterally
      for 5 min. After ischemia, each gerbil was graded neurologically and received an
      ip injection of dichloroacetate (75 or 225 mg/kg) or an equal volume (5 mL/kg) of
      sodium acetate (66 mg/kg). On the following morning, gerbils received a second
      injection, and 3 d later were anesthetized and perfused intracardially. Brains
      were processed, and stained sections were analyzed for neuronal damage. Gerbils
      treated with 225 mg/kg dichloroacetate exhibited significantly less damage than
      the untreated group (p = 0.05, Dunn's test). Gerbils with a normal neurologic
      score evidenced no neuronal damage. Abnormal neurologic scores immediately after
      ischemia did not correlate with degree of neuronal damage observed 4 d later.
      These results indicate that neuronal damage is less in gerbils treated after
      ischemia with an appropriate dose of dichloroacetate. The lack of any
      histological evidence for an adverse effect of dichloroacetate in the controls
      supports the safety of this drug in this protocol. Normal neurologic scores
      immediately after ischemia can be used to identify gerbils mimicking ischemia in
      this model.

PMID- 7710923
TI  - Expanded programme on immunization. Strategies to minimize nosocomial measles
      transmission.

PMID- 7710924
TI  - Interleukin 12: a new clinical player in cytokine therapy.

PMID- 7710925
TI  - Effect of tumour necrosis factor on the uptake of specific and control monoclonal
      antibodies in a human tumour xenograft model.
AB  - The investigations reported in this paper aim to exploit tumour necrosis factor
      (TNF)-induced vascular changes in an attempt to increase the tumour uptake of
      specific monoclonal antibody. The vascular permeability to monoclonal antibody of
      a human tumour xenograft increased 2.6-fold by 1 h post injection of 2.5 x 10(3)
      U of TNF, although this effect was lost by 3 h. The normal tissues also
      demonstrated increased vascular permeability to IgG, but to a lesser extent.
      Liver permeability increased 1.5-fold at 1 h but returned to the control value by
      6 h. Lung permeability increased 1.4-fold at 1 h post injection and returned to
      normal by 3 h. Muscle values were not significantly increased compared with
      controls. The blood activity was cleared more quickly in the TNF-treated mice
      (t1/2 beta = 101 h, compared with 121 h in control mice). This was probably due
      to the increased vascular permeability in normal organs of treated mice. At 1 day
      and 3 days post injection, the tumour uptake of the specific, but not the
      control, antibody was significantly increased by 25% and 29% respectively. This
      resulted in an increase in the area under the tumour activity curve, and
      therefore tumour radiation dose, of 25% in treated compared with control mice. In
      addition, a consequence of the faster blood clearance of the isotope in the TNF
      treated mice was a reduction in the area under the blood activity curve of 12%,
      thereby reducing systemic toxicity. The increase in vascular permeability to IgG
      following TNF injection resulted in both specific and control antibodies having
      improved access to the tumour antigens, and a transient increase in uptake was
      observed. Only in the case of the specific antibody was the increase maintained,
      since this antibody binds to the available antigenic sites, whereas the control
      antibody was cleared from the tumour without binding. No evidence of tumour
      necrosis was observed at the TNF doses given, nor was there any toxicity to the
      mice.

PMID- 7710926
TI  - Allelic imbalance of chromosome 6q in ovarian tumours.
AB  - Previous work has implicated putative tumour-suppressor (ts) genes at 6q27 and a
      broad region at 6p12-q23. Here we report the results of a coded, randomised study
      of allelic imbalance at 12 loci on 6q on 40 pairs of coded tumour-blood pairs
      from patients with ovarian tumours. Our results provide clear evidence for the
      involvement of different regions of 6q in tumours of different histological
      subtypes. The involvement in serous tumours of a ts gene at the distal site is
      confirmed. However, proximal 6q presents a complex picture, with possibly three
      further ts genes: one at 6q21-23.3 involved at high frequency in benign and
      endometrioid tumours, another at 6q14-q15, also involved in endometrioid tumours,
      and a third suggested by a smallest region of deletion at 6q16.3-q21, between
      D6S275 and D6S300, that appears to be involved in early stage tumours. These
      observations point the way to a statistical study of the involvement of 6q in
      tumours of different histological type and staging performed on larger cohorts of
      samples.

PMID- 7710927
TI  - Inhibition of N-linked glycosylation of P-glycoprotein by tunicamycin results in
      a reduced multidrug resistance phenotype.
AB  - Characterisation of altered glycosylation of P-glycoprotein (P-gp) found
      associated with the absence of a multidrug resistance (MDR) phenotype in cell
      lines prompted an investigation to assess the role of post-translational
      processing in establishing P-gp efflux pump functionally. The clone A cell line
      used in this study displays a strong MDR phenotype mediated by high constitutive
      levels of expression of P-gp. Incubation of clone A cells with tunicamycin for
      different periods resulted in a time-dependent increase in daunorubicin
      accumulation, reflecting a reduction in P-gp function. Parallel experiments
      conducted with verapamil resulted in no loss of P-gp functionality in clone A
      cells. Reduction in surface-associated P-gp following exposure to tunicamycin was
      established by FACS analysis, Western blot analysis and immunoprecipitation of
      surface-iodinated P-gp. In addition, immunoprecipitation of P-gp from 32P
      orthophosphate-labelled cells demonstrated reduced phosphorylation of P-gp
      associated with tunicamycin exposure. From these studies we conclude that
      glycosylation of P-gp is required to establish the cellular MDR phenotype.

PMID- 7710928
TI  - Characterisation of high-level cisplatin-resistant cell lines established from a
      human hepatoma cell line and human KB adenocarcinoma cells: cross-resistance and
      protein changes.
AB  - Human liver carcinoma cells (BEL-7404) and human KB adenocarcinoma cells were
      selected by stepwise increases in cisplatin. Drug sensitivity assays indicated
      that the IC50 value for 7404-CP7.5 cells was 49 micrograms ml-1 cisplatin, 111
      fold higher than for the parental hepatoma cells. The IC50 value for KB-CP10
      cells was 38 micrograms ml-1 cisplatin, which is 1152-fold higher than for the
      parental KB cells. The 7404-CP7.5 cells were cross-resistant to methotrexate (39
      x), 5-fluorouracil (23 x) and 6-mercaptopurine (13 x), but were sensitive to
      drugs which are known substrates for the multidrug transporter (P-glycoprotein),
      including colchicine, vinblastine and actinomycin D. Similar cross-resistance
      patterns were observed for KB-CP10 cells. No evidence of DNA amplification or
      expression of the MDR1 gene was found. One-dimensional sodium dodecyl sulphate
      polyacrylamide gel electrophoresis showed increases in 52 kDa protein(s) in both
      the soluble cytosolic and crude membrane fractions in 7404-CP(r) cells and in KB
      CP(r) cells. The amount of 52 kDa protein was proportional to the degree of
      resistance of the 7404-CP(r) cells to cisplatin. Two-dimensional gel analysis
      demonstrated that two polypeptides of molecular mass 52 and 50 kDa were
      overexpressed in the membrane fractions in both 7404-CP20 and KB-CP20 cells.
      Using amino acid microsequencing and Western blotting, major 52 kDa protein was
      identified as the mitochondrial heat shock protein hsp60. Two-dimensional gels of
      [35S]methionine-labelled polypeptides showed many other changes, including
      reduction in soluble proteins of approximately 57 kDa molecular weight in KB-CP20
      cells, and of 35 kDa in both 7404-CP20 and KB-CP20 cells. These results suggest
      that alterations of certain proteins occur commonly in cisplatin-resistant cells,
      particularly proteins of molecular weight 52 and 50 kDa.

PMID- 7710929
TI  - Cellular basis for differential sensitivity to cisplatin in human germ cell
      tumour and colon carcinoma cell lines.
AB  - Cisplatin (CDDP) resistance mechanisms were studied in a model of three germ cell
      tumour and three colon carcinoma cell lines representing intrinsically CDDP
      sensitive and -resistant tumours respectively. The CDDP sensitivity of the cell
      lines mimicked the clinical situation. The glutathione levels of the cell lines
      correlated with CDDP concentrations inhibiting cell survival by 50% (IC50); total
      cellular sulphydryl content (TSH) was unexpectedly inversely correlated with
      IC50. IC50 correlated neither with glutathione S-transferase (GST) nor with GST
      pi expression, topoisomerase I or II activity. Immediately after 4 h incubation
      with CDDP, platinum (Pt) accumulation and Pt bound to DNA were not correlated,
      but after another 24 h drug-free culture, Pt binding to DNA in germ cell tumour
      but not in colon carcinoma cell lines correlated with IC50. With the exception of
      in vitro sensitivity and TSH, none of the parameters studied discriminated
      between the two groups of cell lines. Correction of CDDP sensitivity parameters
      for phenotypical differences did not influence statistical correlations. Analysis
      of variance revealed a correlation between IC50 and the combination of
      glutathione, GST activity and Pt bound to DNA. But at other CDDP cytotoxicity
      levels sensitivity was also correlated with Pt accumulation, topoisomerase II
      activity and TSH in various combinations. This model of intrinsic CDDP resistance
      showed that multiple parameters ought to be studied to explain CDDP resistance,
      but did not elucidate the cause of the unique sensitivity of germ cell carcinoma,
      although the unexpected values of TSH deserve further attention.

PMID- 7710930
TI  - Effects of n-3 fatty acids during neoplastic progression and comparison of in
      vitro and in vivo sensitivity of two human tumour cell lines.
AB  - Several studies have shown that dietary lipid exerts an effect on carcinogenesis.
      We report here that progression to malignancy in vitro is associated with changes
      in the response to fatty acids (FAs). Tumorigenic (THKE) cells were more
      sensitive to the n-3 FAs eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA) than immortalised (IHKE) cells. The growth of THKE cells was inhibited 25%
      more than the growth of IHKE cells at 80 microM EPA (P < 0.01) and 35% more at 40
      microM DHA (P < 0.001). Furthermore, the results indicate that there is a wide
      cell type variation in the response to FAs. We found that the in vitro inhibition
      by FAs correlated with the reduction in the growth rate of the tumour in nude
      mice fed K85 (55% EPA and 30% DHA). A significant difference in tumour latency
      was observed for the A427 cell tumour groups (10 days, P < 0.05). Tumours in the
      animals fed n-3 FA exhibited significantly higher levels of EPA and DHA; the
      level of arachidonic acid (ARA) was significantly lower in THKE tumours and the
      level of linoleic acid (LA) was significantly lower in A427 tumours than in
      controls fed corn oil. The higher sensitivity of the A427 cell line was not
      explained by higher uptake of EPA/DHA.

PMID- 7710931
TI  - Comparison of ability of protein kinase C inhibitors to arrest cell growth and to
      alter cellular protein kinase C localisation.
AB  - Inhibitors of protein kinase C (PKC) such as the staurosporine analogues UCN-01
      and CGP 41251 possess antineoplastic properties, but the mechanism of their
      cytostatic action is not understood. We tested the hypothesis that the ability of
      these compounds to arrest growth is intrinsically linked with their propensity to
      inhibit PKC. Compounds with varying degrees of potency and specificity for PKC
      were investigated in A549 and MCF-7 carcinoma cells. When the log values of drug
      concentration which arrested cell growth by 50% (IC50) were plotted against the
      logs of the IC50 values for inhibition of cytosolic PKC activity, two groups of
      compound could be distinguished. The group which comprised the more potent
      inhibitors of enzyme activity (calphostin C, staurosporine and its analogues UCN
      01, RO 31-8220, CGP 41251) were the stronger growth inhibitors, whereas the
      weaker enzyme inhibitors (trimethylsphingosine, miltefosine, NPC-15437, H-7, H
      7I) affected proliferation less potently. GF 109203X was exceptional in that it
      inhibited PKC with an IC50 in the 10(-8) M range, yet was only weakly cytostatic.
      To substantiate the role of PKC in the growth inhibition caused by these agents,
      cells were depleted of PKC by incubation with bryostatin 1 (1 microM). The
      susceptibility of these enzyme-depleted cells towards growth arrest induced by
      staurosporine, RO 31-8220, UCN-01 or H-7 was studied. The drug concentrations
      which inhibited incorporation of [3H]thymidine into PKC-depleted A549 cells by
      50% were slightly, but not significantly, lower than significantly, lower than
      those observed in control cells. These results suggest that PKC is unlikely to
      play a direct role in the arrest of the growth of A549 and MCF-7 cells mediated
      by these agents. Staurosporine is not only a strong inhibitor of PKC but also
      mimics activators of this enzyme in that it elicits the cellular redistribution
      of certain PKC isoenzymes. The ability of kinase inhibitors other than
      staurosporine to exert a similar effect was investigated. Calphostin C, H-7, H
      7I, miltefosine, staurosporine, UCN-01, RO 31-8220, CGP 41251 or GF 109203X were
      incubated for 30 min with A549 cells in the absence or presence of the PKC
      activator 12-O-tetradecanoyl phorbol-13-acetate. The subcellular distribution of
      PKC-alpha-, -epsilon and -zeta was measured by Western blot analysis. None of the
      agents affected PKC-alpha or -zeta.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7710932
TI  - The interaction with tubulin of a series of stilbenes based on combretastatin A
      4.
AB  - A series of stilbenes, based on combretastatin A-4, were synthesised. A structure
      activity study was carried out to characterise the interaction of these agents
      with tubulin. The substitution of small alkyl substituents for the 4'-methoxy
      group of combretastatin A-4 and the loss of the 3'-hydroxyl group does not have a
      major effect on the interaction with tubulin. trans-Stilbenes were shown to bind
      tubulin, but do not inhibit microtubule assembly. This work, together with
      previous studies, has been used to propose an idealised structure for a tubulin
      binding agent of this type.

PMID- 7710933
TI  - Induction of hepatic metallothionein I in tumour-bearing mice.
AB  - Metallothionein (MT) is an intracellular metal-binding protein which has been
      implicated in various biological roles, including heavy-metal detoxification and
      zinc and copper homeostasis, and has putative antioxidant properties. High levels
      of MT have been detected in certain human tumours, but its functions are unclear.
      The presence of tumour may cause stress conditions along with alterations in host
      metabolism, such as the redistribution of metals and, subsequently, in changes in
      hepatic MT isoforms. The distribution of basal levels of MT-1 and MT-11 isoforms
      in livers of different strains of mice and their induction in mice inoculated
      with tumour cells are investigated. While Balb-c, C57/BL and CD1 mice strains had
      an equal distribution of both hepatic MT isoforms, MT-I and MT-II. In addition,
      MT-I was the predominant isoform synthesised (> 88%) in the livers of all strains
      of mice at 24 h after injection with either cadmium or zinc salts. After
      inoculation with human testicular T7800 or T7799 tumour cells, the major form of
      MT induced in the livers of nude (nu/nu) mice was Zn-MT-I, and its concentration
      was positively correlated with the size of the inoculated tumours (r2 = 0.85). A
      similar positive relation was found in the livers of Balb-c mice inoculated with
      MM45T mouse bladder tumour cells (r2 = 0.96). Following surgical removal of T7800
      tumour, hepatic MT concentrations returned to basal values. There was an increase
      in plasma MT levels in tumour-bearing mice and it was positively correlated with
      the increase in hepatic MT levels. These results demonstrate a specific increase
      in hepatic MT-I isoform in tumour-bearing mice, and this may be due to a
      generalised stress during tumour growth.

PMID- 7710934
TI  - DNA fragmentation induced by the antimitotic drug estramustine in malignant rat
      glioma but not in normal brain--suggesting an apoptotic cell death.
AB  - Estramustine, a combination of 17 beta-oestradiol and nor-nitrogen mustard, has
      been shown to be metabolised and to induce specific antiproliferative effects in
      malignant glioma, including arrest of glioma cells in the G2/M phase of the cell
      cycle, damage to cell membranes and DNA and induction of free oxygen radicals. To
      evaluate further the effects of estramustine, an in vivo rat glioma model using
      inbred BD-IX rats and the BT4C cell line was set up. In order to detect cells
      with fragmented DNA, tumour and brain specimens were, following fixation for
      histological examination, processed for in situ end labelling (ISEL) with biotin
      labelled nucleotides. Fresh tissue fragments were also used for DNA integrity
      analysis on agarose gels. It was demonstrated that estramustine induced clusters
      of ISEL-positive cells and a pronounced typical fragmentation of DNA 0.5-8 h
      after treatment. In tumours examined 24 or 94 h after estramustine treatment, and
      in untreated tumours, only occasional single ISEL-positive cells were scattered
      in the tumour. DNA from normal brain tissue did not display any visible sign of
      fragmentation. These changes are indicative of programmed cell death induced by
      estramustine in glioma cells but not in normal brain tissue. Further studies are,
      however, needed to establish in detail the mechanism of cell death following
      treatment with the antimitotic drug estramustine.

PMID- 7710935
TI  - Vascularity and perfusion of human gliomas xenografted in the athymic nude mouse.
AB  - The vascularisation and perfusion of seven subcutaneously xenografted human
      glioma lines established from surgical specimens has been analysed using an anti
      collagen type IV antibody to visualise the vascular walls in combination with a
      perfusion marker (Hoechst 33342). A computer-based digital image processing
      system was employed for quantitative analysis of the parameters. The vascular
      architecture of individual tumours belonging to the same tumour line showed a
      consistent similarity, while substantial differences occurred between the various
      tumour lines derived from different patients. Despite the presence of a large
      inter-tumour variation in vascular area as a proportion of the tumour area, this
      vascular parameter clearly showed tumour line-specific characteristics. The
      perfused fraction of the tumour vessels also showed a large inter-tumour
      variation for all tumour lines ranging from 20% to 85%, but the majority of
      tumours of all lines had perfusion fractions of more than 55%. Despite large
      variation, the perfused vascular area as a proportion of the tumour cross
      sectional area exhibited clear tumour line-specific tendencies. These
      observations suggest that consistent differences in vascular parameters are
      present between glioma xenograft lines, although the tumour lines all originated
      from histologically similar human high-grade gliomas. These differences may have
      important consequences for treatment and clinical behaviour of this type of
      tumour.

PMID- 7710936
TI  - Effect of axial ligation and delivery system on the tumour-localising and 
      photosensitising properties of Ge(IV)-octabutoxy-phthalocyanines.
AB  - Four Ge(IV)-octabutoxy-phthalocyanines (GePcs) bearing two alkyl-type axial
      ligands were assayed for their pharmacokinetic properties and phototherapeutic
      efficiency in Balb/c mice bearing an intramuscularly transplanted MS-2
      fibrosarcoma. The GePcs were i.v. injected at a dose of 0.35 mumol kg-1 body
      weight after incorporation into either Cremophor emulsions or small unilamellar
      liposomes of dipalmitoyl-phosphatidylcholine (DPPC). Both the nature of the
      delivery system and the chemical structure of the phthalocyanine were found to
      affect the behaviour of the GePcs in vivo. Thus, Cremophor-administered GePcs
      invariably yielded a more prolonged serum retention and a larger association with
      low-density lipoproteins (LDLs) as compared with the corresponding liposome
      delivered phthalocyanines. This led to a greater efficiency and selectivity of
      tumour targeting. These effects were more pronounced for those GePcs having
      relatively long alkyl chains (hexyl to decyl) in the axial ligands. Maximal
      tumour accumulation (0.67 nmol per g of tissue) was found for Ge-Pc(hexyl)2 at 24
      h after injection. Consistently, the Ge-Pc(hexyl)2, administered via Cremophor,
      showed the highest phototherapeutic activity towards MS-2 fibrosarcoma.

PMID- 7710937
TI  - Adjuvant intraoperative photodynamic therapy diminishes the rate of local
      recurrence in a rat mammary tumour model.
AB  - The use of photodynamic therapy (PDT) as an adjunct to curative tumour resection
      was investigated in a tumour recurrence model, using rat mammary adenocarcinoma
      BN472. Tumours were inoculated subcutaneously in 60 animals and resected after 21
      days of growth. Immediately after removal, the operation site was exposed to 320
      450 nm light of 0.1 W cm-2 and 60 J cm-2 after photosensitisation with either
      Photofrin (5 mg kg-1 i.v. 48 h before illumination) or 5-aminolaevulinic acid
      (ALA) (2 mg ml-1 in drinking water for 9 days). Porphyrin concentrations were
      measured in tissue samples. After 28 days, animals treated with adjunctive PDT
      had a significantly longer tumour-free interval than controls (P < 0.01); median
      25 days (Photofrin), 18 days (ALA), 14 days (controls). Moreover, in the PDT
      groups significantly fewer rats had lymph node metastasis. A prophyrin
      concentration ratio between tumour and mammary tissue of 2:1 was found after
      Photofrin and 4:1 after ALA. The results indicate that adjuvant intraoperative
      PDT may be a safe and effective method of destroying residual tumour, thereby
      preventing locoregional tumour recurrence.

PMID- 7710938
TI  - Buthionine sulphoximine-mediated sensitisation of etoposide-resistant human
      breast cancer MCF7 cells overexpressing the multidrug resistance-associated
      protein involves increased drug accumulation.
AB  - Preincubation of etoposide-resistant human MCF7 breast cancer cells (MCF7/VP)
      with buthionine sulphoximine (BSO) resulted in their sensitisation to etoposide
      and vincristine. Chemosensitisation was accompanied by elevated intracellular
      drug levels. In contrast, simultaneous exposure to BSO did not result in
      increased drug accumulation. Similar, but quantitatively smaller, effects were
      also observed when sensitive wild-type MCF7/WT cells were treated with BSO. In
      agreement with its effect on drug accumulation, BSO pretreatment also increased
      VP-16-stimulated cleavable complex formation between DNA topoisomerase II and
      cellular DNA. BSO treatment also led to a significant increase in acid
      precipitable VP-16 levels in MCF7/VP, but not MCF7/WT cells. In contrast, no
      clear effects of BSO on drug efflux were observed and drug retention was only
      minimally increased after BSO treatment of both MCF7/WT and MCF7/VP cells and no
      difference between the two cell lines was detected. Thus, chemosensitisation by
      BSO appeared to be mediated through increased intracellular drug concentrations
      and/or protein binding.

PMID- 7710940
TI  - Targeting gene transcription: a new strategy to down-regulate c-erbB-2 expression
      in mammary carcinoma.
AB  - Overexpression of the c-erbB-2 proto-oncogene in mammary carcinoma is frequently
      associated with amplification of the c-erbB-2 gene, but it also occurs from
      single-copy gene. Studies in mammary-derived cell lines have shown that, whether
      or not the gene is amplified, there is a 6- to 8-fold increase in the
      accumulation of c-erbB-2 mRNA per gene copy in overexpressing cells. We have
      recently shown that this phenomenon is due to increased activity of the c-erbB-2
      promoter mediated by the binding of a novel transcription factor, OB2-1, which is
      present at higher levels in overexpressing cells than in low expressors. OB2-1
      activity therefore represents a novel therapeutic target for the down-regulation
      of c-erbB-2 levels in human cells. As a prototype for this strategy, we show here
      that the drug sodium aurothiomalate is able to inhibit the DNA-binding activity
      of OB2-1 in vitro and also to interfere with c-erbB-2 promoter activity in cell
      based transfection assays. In addition, endogenous c-erbB-2 immunoreactivity was
      reduced in cells treated with aurothiomalate as compared with the levels observed
      in control cells.

PMID- 7710939
TI  - Inhibition of hepatocyte growth factor-induced motility and in vitro invasion of
      human colon cancer cells by gamma-linolenic acid.
AB  - In this study we have determined the effects of the n-6 essential fatty acid
      gamma-linolenic acid (GLA) on the motility and invasive/metastatic nature of the
      human colon cancer cell lines HT115, HT29 and HRT18. Cell motility was induced by
      hepatocyte growth factor/scatter factor (HGF/SF) and measured by both colony
      scattering and dissociation from carrier beads. Invasiveness was measured in
      vitro by cellular invasion into extracellular matrix. At concentrations up to 100
      microM (which had no effect on cell growth over the duration of the experiments)
      both cell motility and invasion induced by HGF/SF were markedly reduced by GLA
      and its lithium salt. The attachment of these cells to the extracellular matrix
      components (Matrigel and fibronectin) was also inhibited. There were also changes
      in the cell-surface E-cadherin, but not fibronectin receptor at similar
      concentrations. It is concluded that n-6 essential fatty acids have the ability
      to inhibit both motility and invasiveness of human colon cancer cells, perhaps by
      modifying cell-surface adhesion molecules.

PMID- 7710941
TI  - c-erbB-3 protein expression in ovarian tumours.
AB  - In this study the expression of c-erbB-3 protein was investigated in a range of
      human ovarian tumours using a monoclonal antibody (RTJ1) raised to a synthetic
      peptide from the cytoplasmic domain of the human c-erbB-3 protein. A total of 73
      samples from 71 patients were graded as negative, weak, moderate or strong
      according to the intensity of immunohistochemical staining observed, and this was
      related to tumour characteristics and other clinical parameters. In terms of
      positivity vs negativity, of the 73 samples examined, 62 (85%) showed positive
      immunohistochemical staining for c-erbB-3. The majority of all ovarian tumours
      studied were positive for c-erbB-3 regardless of whether they were malignant
      (89%), borderline (100%) or benign (61%), however the incidence of positivity was
      significantly less in the benign group than in overtly malignant tumours (P =
      0.03). c-erbB-3 positivity was not significantly associated with either age at
      diagnosis, tumour stage, differentiation, ploidy, percentage in S-phase or post
      operative tumour bulk in malignant tumours. In terms of intensity of staining no
      significant difference was observed either within the common epithelial group or
      between this group and tumours of a benign nature. A significantly more intense
      pattern of c-erbB-3 staining was observed in tumours of borderline malignancy
      when compared with their overtly malignant counterparts (P = 0.002). Patients
      presenting with early-stage malignant tumours (I/II) were more likely to display
      intense tumour staining than those with late-stage disease (III/IV) (P = 0.04).
      These investigations suggest that c-erbB-3 protein is frequently expressed in
      both benign and malignant ovarian tumours, and that overexpression is more common
      in borderline and early invasive lesions.

PMID- 7710942
TI  - Characterisation of aberrant crypt foci in carcinogen-treated rats: association
      with intestinal carcinogenesis.
AB  - Carcinogen-treated rats develop foci of aberrant crypts in the colon (ACFs) that
      have been interpreted as preneoplastic lesions. To characterise ACFs further, we
      studied in the unsectioned colon of rats the number, multiplicity, some
      morphological characteristics and the type of mucin production in ACFs. In ACFs
      observed 115 days after the administration of 50 mg kg-1 1,2-dimethylhydrazine
      (DMH), crypt multiplicity [number of aberrant crypts (AC) per focus] was
      positively correlated (P < 0.0001) with the reduction of goblet cells, and with
      luminal and nuclear alterations in the cells surrounding the lumen of the ACs. We
      studied mucin production in the unsectioned colon, demonstrating that ACFs
      producing sulphomucins (like the normal distal rat colon) were progressively
      reduced when ACF multiplicity increased, whereas ACFs containing sialomucins
      (correlated with an increased risk of colon cancer) or both sulphomucins and
      sialomucins increased with crypt multiplicity. We also studied ACFs in the colon
      and the occurrence of intestinal tumours in rats treated with azoxymethane (AOM;
      64 mg kg-1). A significant association was found (P = 0.04) between tumours and
      the presence of 'large' ACFs (AC/ACF > 14 crypts) and a borderline significant
      association (P = 0.057) between the presence of tumours and sialomucin-producing
      ACFs. We found no association between the number of ACFs, ACF multiplicity and
      the presence of tumours.

PMID- 7710943
TI  - Tumour promoter activity in Malaysian Euphorbiaceae.
AB  - Herbal medication has been practised by the rural Malaysian Malays for a long
      time. However, the long-term side-effects have never been studied. In the present
      study, 48 species of Euphorbiaceae were screened for tumour-promoter activity by
      means of an in vitro assay using a human lymphoblastoid cell line harbouring the
      Epstein-Barr virus (EBV) genome. Twenty-seven per cent (13 out of 48) of the
      species tested were found to be positive, and in four species, namely Breynia
      coronata Hk.f, Codiaeum variegatum (L) Bl, Euphorbia atoto and Exocoecaria
      agallocha, EBV-inducing activity was observed when the plant extracts were tested
      at low concentrations of between 0.2 and 1.2 micrograms ml-1 in cell culture.
      This observation warrants attention from the regular users of these plants
      because regular use of plants with tumour-promoting activity could well be an
      aetiological factor for the promotion of tumours among rural Malaysian Malays.

PMID- 7710944
TI  - Molecular mechanisms of tirapazamine (SR 4233, Win 59075)-induced hepatocyte
      toxicity under low oxygen concentrations.
AB  - Previously we showed that tirapazamine (SR 4233, Win 59075) is cytotoxic towards
      hepatocytes under conditions of hypoxia but not in 10% or 95% oxygen and that
      bioreduction by DT-diaphorase or cytochrome P450 is not a major pathway. In the
      present study, we report that tirapazamine is highly cytotoxic to isolated rat
      hepatocytes maintained under 1% oxygen and the molecular cytotoxic mechanism has
      been elucidated. Cytotoxicity was prevented by the cytochrome P450 2E1 inhibitors
      phenyl imidazole, isoniazid, isopropanol or ethanol, suggesting that cytochrome
      P450 2E1 catalysed tirapazamine reductive bioactivation. By contrast, dicoumarol,
      a DT-diaphorase inhibitor, markedly increased tirapazamine-induced cytotoxicity.
      Cytotoxicity was also inhibited in normal but not DT-diaphorase-inactivated
      hepatocytes by increasing cellular NADH levels with lactate or ethanol or the
      mitochondrial respiratory inhibitors. Evidence that oxygen activation contributed
      to cytotoxicity was that glutathione oxidation occurred well before cytotoxicity
      ensued and that tirapazamine was more cytotoxic towards catalase- or glutathione
      reductase-inactivated hepatocytes. Furthermore, polyphenolic antioxidants such as
      quercetin, caffeic acid or purpurogallin, the radical trap Tempol or the iron
      chelator desferrioxamine prevented tirapazamine-mediated cytotoxicity. However,
      the antioxidants diphenylphenylenediamine, butylated hydroxyanisole or butylated
      hydroxytoluene did not prevent cytotoxicity and malonaldehyde formation was not
      increased, suggesting that lipid peroxidation was not important. The above
      results suggest that DT-diaphorase detoxifies tirapazamine whereas reduced
      cytochrome P450 reduces tirapazamine to a nitrogen oxide anion radical which
      forms cytotoxic reactive oxygen species as a result of redox cycling.

PMID- 7710945
TI  - Annexin VI has tumour-suppressor activity in human A431 squamous epithelial
      carcinoma cells.
AB  - In this study we show that heterologous expression of annexin VI in A431 squamous
      carcinoma cells caused a marked suppression of tumour cell growth when cells were
      cultured subcutaneously in nude mice. The tumours formed by the annexin VI+ A431
      cells were morphologically and histologically similar to those formed by the wild
      type cells.

PMID- 7710946
TI  - Interleukin 1 modulates growth of human renal carcinoma cells in vitro.
AB  - We have investigated the influence of interleukin 1 (IL-1) on growth of human
      renal carcinoma cells in vitro. Using a capillary soft-agar cloning system, 18%
      of freshly explanted renal carcinomas were stimulated to grow by IL-1 and 4% were
      inhibited. Subsequent experiments with established renal cancer cell lines
      demonstrated that two out of four cell lines (Caki-2, A-498) were sensitive to IL
      1. [3H]Thymidine incorporation as well as monolayer growth was enhanced in Caki-2
      cells in the presence of high (10%) and low (1%) serum concentrations. Although
      clonogenic growth of A-498 cells was stimulated by IL-1, overall [3H]thymidine
      incorporation and monolayer proliferation were decreased. Using radioligand
      experiments, 250 cell-surface receptors of high affinity (KD 4.5 x 10(-11) M) and
      2500 receptors of low affinity (KD 1.3 x 10(-9) M) were detected on A-498 cells.
      IL-1 binding was reduced under the influence of IL-1. Competition experiments
      with inhibiting antibodies against IL-1 receptor type I and type II revealed that
      signal transduction was performed via type I receptors. After cross-linking to IL
      1, receptor type I was immunoprecipitated using anti-IL-1 antibodies. We
      hypothesise that, since IL-1 modulates in vitro growth of a subgroup of human
      renal cancer cells, interference with its mechanism of action may be of potential
      value in order to modulate tumour proliferation.

PMID- 7710947
TI  - Bacillus Calmette-Guerin (BCG) enhances monocyte- and lymphocyte-mediated bladder
      tumour cell killing.
AB  - A cytotoxicity assay was used to study the action of bacillus Calmette-Guerin
      (BCG) and cytokines on four human bladder cancer cell lines. Monocytes and
      lymphocytes from peripheral blood were incubated with or without BCG or cytokines
      for 24 h, after which [3H]thymidine-labelled target cells were added and the 72 h
      percentage specific release determined. BCG had a direct cytotoxic effect against
      tumour cells and significantly enhanced monocyte/macrophage and enhanced
      lymphocyte cytotoxicity against one cell line (UCRU-BL-17). Supernatants (SNs)
      from BCG-activated monocytes/macrophages and lymphocytes increased the percentage
      specific release of [3H]thymidine from UCRU-BL-17 cells. Interferon alpha (IFN
      alpha) and interleukin 2 (IL-2) were cytotoxic towards UCRU-BL-17. No synergy
      occurred between BCG and cytokines at the concentrations tested. The results
      suggest that BCG is superior to IFN-alpha, interferon gamma (IFN-gamma) and IL-2
      in enhancing cell-mediated cytotoxicity.

PMID- 7710948
TI  - Oncogene-linked in situ immunotherapy of pre-B lymphoma arising in E mu/ret
      transgenic mice.
AB  - We attempted to induce anti-tumour immunity for rejecting pre-B lymphoma derived
      from E mu/ret transgenic mice (TGM). We established pre-B-lymphoma cell lines of
      C57BL/6 x Balb/c background (H-2b/d) into which H-2k alloantigen and C3H
      background were introduced (retL1-6 and retL6-6), and we inoculated BCF1 mice
      with these immunising tumour cells. After these tumours were rejected by
      alloantigen (H-2k/C3H background)-specific effector cells, the mice were
      challenged with the pre-B-lymphoma cell line derived from the original E mu/ret
      TGM (ret0-2). All non-immunised control mice died within 80 days, whereas half
      the immunised mice survived for over 300 days. The immunity was also effective
      against primary pre-B-lymphoma cells from E mu/ret TGM and the ret-driven
      melanoma cell line (MEL-ret), but not against the pre-B-lymphoma cell line from E
      mu/myc TGM. This immunity was at least in part mediated by cell-mediated
      cytotoxicity that was specific to the ret oncogene product or ret-regulated
      antigen. Next we immunised E mu/ret TGM by inoculating them with retL6-6 cells
      once every 2 weeks beginning at the age of 1 month. Interestingly, this
      immunisation enabled the TGM to survive longer than the non-immunised control
      group (P < 0.05). Moreover, 2 of 11 transgenic mice receiving such immunisation
      were free from both macroscopic and microscopic tumours at the time when all of
      the 12 non-immunised control TGM had died from their tumour. This provides a new
      model for oncogene-linked immunotherapy research.

PMID- 7710949
TI  - Loss of heterozygosity occurs at the D11S29 locus on chromosome 11q23 in invasive
      cervical carcinoma.
AB  - Allelotypic detection of loss of heterozygosity (LOH) has been used to identify
      putative tumour-suppressor genes. Loci on human chromosome 11q23 are frequently
      altered in malignant disease, and LOH has been reported at an anonymous D11S29
      locus at 11q23 in a proportion of breast and ovarian cancers and malignant
      melanomas. Previous studies have reported a high frequency of LOH in cervical
      carcinoma mapping to 11q23. Using polymerase chain reaction techniques employing
      probes for a recently described polymorphic dinucleotide microsatellite within
      this locus, we have searched for LOH in 69 cases of invasive cervical carcinoma.
      Genomic material was microdissected from sections cut from archival paraffin
      embedded material, using the patients' constitutional genotype as a control Sixty
      two (90%) of the cases were informative, and LOH occurred in 25/62 (40%) of
      tumours. Loss of an arm or single chromosome 11 is a well-recognised event in
      cervical carcinoma, and by employing other microsatellite polymorphisms mapping
      to 11q13 and 11p11-p12 we excluded those cases with widespread allelic loss. By
      doing so, LOH at D11S29 was found in 16/53 (30%) of tumours. The findings suggest
      a putative tumour-suppressor gene on 11q involved in cervical carcinogenesis.

PMID- 7710950
TI  - p53 mutations, protein expression and cell proliferation in squamous cell
      carcinomas of the head and neck.
AB  - Thirty-three patients with squamous cell carcinoma of the head and neck region
      were studied concerning p53 protein expression and mutations in exons 4-9 of the
      p53 gene using immunohistochemistry, polymerase chain reaction (PCR)-single
      strand conformation polymorphism analysis and DNA sequencing. Immunoreactivity
      was found in 64% and p53 gene mutations in 39% of the tumours. Thirty-three per
      cent of the immunopositive and 50% of the immunonegative tumours were mutated
      within exons 5-8. In one immunopositive tumour three variants of deletions were
      observed. Sequencing of the p53 mutated, immunonegative tumours revealed four
      cases with deletions, one case with a transversion resulting in a stop codon and
      one case with a splice site mutation which could result in omission of the
      following exon at splicing. All mutations in the immunonegative tumours resulted
      in a truncated p53 protein. No association between p53 gene status and expression
      of proliferating cell nuclear antigen (PCNA) or cell proliferation as judged by
      in vivo incorporation of the thymidine analogue iododeoxyuridine (IdUrd) was
      found.

PMID- 7710951
TI  - Retinoblastoma gene mutations in primary human bladder cancer.
AB  - Inactivation of the retinoblastoma (RB) gene is known to be implicated in the
      pathogenesis of several types of human cancers. Since structural alterations of
      the RB gene have not been well examined in human bladder cancer, we looked for
      mutations in the entire coding region of this gene using polymerase chain
      reaction (PCR) and single-strand conformational polymorphism analysis of RNA. We
      also examined allelic loss of the RB gene using PCR-based restriction fragment
      length polymorphism analysis. Of 30 samples obtained from patients with bladder
      cancer, eight (27%) were found to have RB gene mutations. DNA sequencing of the
      PCR products revealed five cases with single point mutations and three cases with
      small deletions. These mutations included one (10%) of ten low-grade (grade 1)
      tumours, four (50%) of eight intermediate-grade (grade 2) tumours and three (25%)
      of 12 high-grade (grade 3) tumours. Likewise, mutations were found in four (21%)
      of 19 superficial (pTa and pT1) tumours and four (36%) of 11 invasive (pT2 or
      greater) tumours. In 15 informative cases, loss of heterozygosity at the RB locus
      was shown in five cases (33%), three cases with RB mutations and two without
      them. These results suggest that RB gene mutations are involved in low-grade and
      superficial bladder cancers as well as in high-grade and invasive cancers.

PMID- 7710952
TI  - Elevated levels of members of the STAT family of transcription factors in breast
      carcinoma nuclear extracts.
AB  - The transcription factor, milk protein binding factor (MPBF/Stat5), is a member
      of the STAT family of signalling molecules which mediates prolactin signal
      transduction in lactating mammary gland by binding to GAS (gamma-interferon
      activation site) DNA elements. We have determined the levels of STAT factors in
      nuclear extracts from a variety of human breast tissues including carcinoma and
      normal 'resting' breast by electrophoretic mobility-shift assay. The results show
      that the level of STAT binding activity is low in normal 'resting' breast and
      benign lesions while carcinoma samples have significantly higher (P < 0.01)
      amounts of STAT binding activity. Supershift analysis suggests that Stat1 and
      possibly other members of the STAT family of signalling factors, including Stat3,
      are activated in breast cancer tissues.

PMID- 7710953
TI  - A new human breast cancer cell line, KPL-1 secretes tumour-associated antigens
      and grows rapidly in female athymic nude mice.
AB  - We recently established a new human breast cell line, designated KPL-1, which was
      derived from the malignant effusion of a patient with breast cancer. This cell
      line is highly tumorigenic and grows rapidly in female nude mice. Cytogenetic
      analysis indicated its human origin and revealed a hypertriploid modal number of
      chromosomes. Electron microscopic examination suggested that the KPL-1 cells are
      of epithelial origin. Immunohistochemical studies revealed that the cells express
      cytokeratin, carcinoembryonic antigen and CA 15-3. They also possess a large
      number of oestrogen receptors but not progesterone receptors. Interestingly, KPL
      1 cells seem to grow oestrogen independently in vitro. No amplification of c-erbB
      2, c-myc, H-ras and N-ras genes was detected. KPL-1 cells secrete a large amount
      of tissue polypeptide antigen (TPA). Although the secretion of CA 15-3 seemed to
      be constant throughout all cell growth phases, TPA secretion increased during the
      exponential growth phase and decreased during the plateau phase. Serum TPA levels
      significantly correlated with the volume of KPL-1 tumours transplanted into nude
      mice. These data suggest that this KPL-1 cell line may be useful for studying
      oestrogen-independent growth and the kinetics of tumour-associated antigens in
      vivo as well as in vitro.

PMID- 7710954
TI  - Modulation of cancer endocrine therapy by melatonin: a phase II study of
      tamoxifen plus melatonin in metastatic breast cancer patients progressing under
      tamoxifen alone.
AB  - Recent observations have shown that the pineal hormone melatonin (MLT) may
      modulate oestrogen receptor (ER) expression and inhibit breast cancer cell
      growth. On this basis, we have evaluated the biological and clinical effects of a
      concomitant MLT therapy in women with metastatic breast cancer who had progressed
      in response to tamoxifen (TMX) alone. The study included 14 patients with
      metastasis who did not respond (n = 3) to therapy with TMX alone or progressed
      after initial stable disease (SD) (n = 11). MLT was given orally at 20 mg day-1
      in the evening, every day starting 7 days before TMX, which was given orally at
      20 mg day-1 at noon. A partial response was achieved in 4/14 (28.5%) patients
      (median duration 8 months). The treatment was well tolerated in all cases, and no
      MLT-induced enhancement of TMX toxicity was seen; on the contrary, most patients
      experienced a relief of anxiety. Mean serum levels of insulin-like growth factor
      1 (IGF-1), which is a growth factor for breast cancer, significantly decreased on
      therapy, and this decline was significantly higher in responders than in patients
      with SD or progression. This pilot phase II study would suggest that the
      concomitant administration of the pineal hormone MLT may induce objective tumour
      regressions in metastatic breast cancer patients refractory to TMX alone.

PMID- 7710955
TI  - Expression of tumour-suppressor gene Rb, apoptosis-suppressing protein Bcl-2 and
      c-Myc have no independent prognostic value in renal adenocarcinoma.
AB  - The expression of retinoblastoma (Rb), c-Myc and Bcl-2 proteins was studied by
      immunohistochemical methods in 104 cases of renal adenocarcinoma. One tumour was
      completely negative for Rb protein and altered expression pattern was detected in
      36% of cases. A low fraction of Rb-positive nuclei was related to high grade (P =
      0.016) and high mitotic index (P = 0.012). Twenty-eight per cent of the tumours
      expressed c-Myc in cancer cell nuclei and 87% showed cytoplasmic positivity.
      Cytoplasmic expression of c-Myc was related to high grade (P = 0.002), while
      nuclear expression of c-Myc was related to small tumour diameter (P = 0.034), low
      T category (P = 0.04), low mitotic index (P = 0.019) and expression of c-ErbB-2
      (P = 0.0007). Overexpression of c-myc predicted favourable outcome in M0 tumours
      (P = 0.0157). Bcl-2 was expressed in 20% of tumours and it was related to small
      tumour size (P < 0.0001), low T category (P < 0.0001), lack of venous invasion (P
      = 0.008), node negativity (P = 0.015) and absence of metastasis (P = 0.017). In
      multivariate analysis the expression of Rb, Bcl-2 and c-Myc had no independent
      prognostic value over T category (P < 0.001), mitotic index (P = 0.008) and
      combined nuclear grade (P = 0.056).

PMID- 7710956
TI  - Preoperative serum levels of CEA and CA 242 in colorectal cancer.
AB  - Preoperative serum levels of CEA and CA 242 were determined in 260 patients with
      colorectal cancer and in 92 patients with benign colorectal diseases. The overall
      sensitivity of the CEA test was 43% and of the CA 242 test 39%. The corresponding
      specificities were 90% and 87% respectively, using 5 ng ml-1 as cut-off level for
      CEA and 20 U ml-1 for CA 242. The sensitivity of CEA was 26%, 32%, 38% and 77%
      for Dukes A, B, C and D colorectal cancer, and the sensitivity of CA 242 was 26%,
      26%, 40% and 67%, respectively. The correlation between CEA and CA 242 was low.
      Concomitant elevation of both markers was seen in 5%, 12%, 18% and 59% of
      patients with Dukes A, B, C and D colorectal cancer, respectively. Of all the
      patients, 23% showed elevation of both the CEA and the CA 242 level, whereas CEA
      alone was elevated in 20% and CA 242 alone in 15% of the patients with colorectal
      cancer. Combined use of both markers raised the overall sensitivity from 43% to
      58%, but reduced the specificity from 90% to 80%. The increase in sensitivity by
      combining the two markers was most marked in Dukes A, B and C colorectal cancer.
      Either or both of the markers were elevated in 46%, 46% and 60% of the patients
      respectively. The clinical value of combining CEA and CA 242 seems very promising
      and should be further investigated in prospective studies.

PMID- 7710957
TI  - Measurement of response to treatment in colorectal liver metastases.
AB  - Assessment of tumour response to chemotherapy is important when assessing
      efficacy of treatment and comparing differing therapeutic regimens. Percentage
      hepatic replacement (PHR) is commonly used to assess response to treatment of
      colorectal hepatic metastases. PHR is dependent not only on tumour volume, but
      also on hepatic parenchymal volume. The effect of tumour growth on hepatic
      parenchymal volume is unclear but is of importance owing to its effect on PHR. We
      assessed tumour and hepatic parenchymal weights in an animal tumour model using
      dissection, and tumour and hepatic parenchymal volumes in patients with
      colorectal hepatic metastases using CT scanning, in order to establish how
      hepatic parenchyma varied with change in metastasis size. There was no
      significant correlation between tumour and liver parenchyma in either the animal
      model (r = -0.03, P > 0.05) or the patient study (r = 0.3, P < 0.05). This
      suggests that hepatic parenchymal volume was preserved in the presence of
      increasing tumour volume. In a further study of computerised tomographic (CT)
      scans before and after treatment in patients whose tumours either responded to
      chemotherapy or continued to grow, change in PHR (median proportion of PHR change
      = 0.40) significantly (P = 0.04) underestimated the change in tumour volume
      (median proportion of tumour volume change = 0.56), particularly at higher (> 400
      ml) volumes. There was good correlation between change in tumour volume and WHO
      criteria in assigning patients to tumour growth, stable disease or tumour
      response categories. This study suggests that, in clinical trials comparing
      colorectal liver metastasis treatments, metastasis volume and not PHR should be
      used to assess extent of disease and the effect of treatment.

PMID- 7710958
TI  - Continuous-infusion verapamil with etoposide in relapsed or resistant paediatric
      cancers.
AB  - This study evaluates the use of a multidrug resistance (MDR) modulator
      (verapamil) in combination with a standard dose of single-agent etoposide in
      relapsed or refractory paediatric malignancy. A total of 20 patients (median age
      6.5 years) were treated with an infusion of verapamil (loading dose 0.1 mg kg-1,
      followed by continuous infusion 0.15 mg kg-1 h-1) for 72 h. Etoposide was given
      daily (150 mg m-2 day-1) for three doses (each over 1 h); the first dose was
      given 12 h into the verapamil infusion. Cardiovascular toxicity was monitored by
      ECG and 2 hourly blood pressure and pulse recordings. Verapamil and norverapamil
      plasma concentrations were measured daily. Disease response was assessed after
      two courses. A total of 29/35 treatment courses were given at the desired
      verapamil dose; five courses required a dose reduction owing to cardiovascular
      toxicity. No patient required intensive monitoring. All patients who developed
      cardiovascular toxicity were over 14 years old. There was no correlation between
      plasma verapamil or norverapamil concentrations and toxicity. There were six
      partial responses (three rhabdomyosarcoma, three neuroblastoma) after two
      courses, but because of variation in the dose and schedule of etoposide these
      cannot be unequivocally contributed to MDR reversal. In conclusion, a regimen
      using a continuous infusion of verapamil combined with divided-dose etoposide is
      tolerable in children, and this strategy may be effective in refractory
      neuroblastoma and rhabdomyosarcoma.

PMID- 7710959
TI  - Socioeconomic status and colon cancer incidence: a prospective cohort study.
AB  - The association between socioeconomic status and colon cancer was investigated in
      a prospective cohort study that started in 1986 in The Netherlands among 120,852
      men and women aged 55-69 years. At baseline, data on socioeconomic status,
      alcohol consumption and other dietary and non-dietary covariates were collected
      by means of a self-administered questionnaire. For data analysis a case-cohort
      approach was used, in which the person-years at risk were estimated using a
      randomly selected subcohort (1688 men and 1812 women). After 3.3 years of follow
      up, 312 incident colon cancer cases were detected: 157 men and 155 women. After
      adjustment for age, we found a positive association between colon cancer risk and
      highest level of education (trend P = 0.13) and social standing (trend P = 0.008)
      for men. Also, male, upper white-collar workers had a higher colon cancer risk
      than blue-collar workers (RR = 1.42, 95% CI 0.95-2.11). Only the significant
      association between social standing and colon cancer risk persisted after
      additional adjustment for other risk factors for colon cancer (trend P = 0.005),
      but the higher risk was only found in the highest social standing category (RR
      highest/lowest social standing = 2.60, 95% CI 1.31-5.14). In women, there were no
      clear associations between the socioeconomic status indicators and colon cancer.

PMID- 7710961
TI  - Cervical cytology reported as negative and risk of adenocarcinoma of the cervix:
      no strong evidence of benefit.
AB  - The relationship between negative cervical cytology reports and risk of
      adenocarcinoma of the cervix was evaluated in a case-control study of 113 cases
      and 452 controls. All cases and controls had received at least two negative
      cytology reports. There was no significant difference between the cases and
      controls in the number of negative cytology reports or in history of cervical
      abnormality; while a test for trend in the time since last negative cytology
      report was significant (P < 0.001), the estimated benefit was very modest.
      Although the estimates of relative protection were higher in women aged less than
      35 years than in women aged 35-69 years, this difference was not statistically
      significant. These results suggest that cervical screening as practised in the
      1970s and 1980s was much less effective in preventing adenocarcinoma than
      squamous carcinoma of the cervix.

PMID- 7710960
TI  - Family history of cancer, body weight, and p53 nuclear overexpression in Duke's C
      colorectal cancer.
AB  - To examine the hypothesis that colorectal carcinomas with and without TP53
      mutations may be characterised by aetiological heterogeneity, we analysed a group
      of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial
      Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53
      overexpression using the monoclonal antibody PAb 1801, and identified 42 (39%)
      patients displaying p53-positive phenotype, defined as > or = 25% of positive
      cells. Patients with two or more first-degree relatives with cancer had an odds
      ratio (OR) of 2.9 (95% CI 1.0-8.3) for p53 overexpression in comparison with
      those without a family history of cancer (trend test, P = 0.11). A possible
      association between body weight and p53 overexpression was observed. The ORs were
      1.9 for the second quartile, 1.9 for the third quartile and 3.4 for the highest
      quartile in comparison with the lowest quartile (trend test, P = 0.06). No
      association between occupational physical activity, smoking, drinking, parity and
      p53 overexpression was identified. The results suggest that p53 overexpression
      may be related to genetic predisposition to colorectal cancer, and p53-positive
      and p53-negative colorectal cancers may be controlled by different aetiological
      pathways.

PMID- 7710962
TI  - British Association for Cancer Research 36th annual meeting jointly with
      Association of Cancer Physicians 10th annual meeting. Nottingham, 2-5 April 1995.
      Abstracts.

PMID- 7710963
TI  - Increased susceptibility to audiogenic seizures following withdrawal of
      progesterone.
AB  - This investigation was performed to verify a previous hypothesis which correlates
      the catamenial seizures with the stoppage of progesterone secretion. White rats
      from a Wistar strain were tested with an electric bell. Thirty-five animals
      refractory to the acoustic stimulus were selected for the experiment. Each animal
      received 9 daily injections with progesterone, 5 mgr/day. The animals were tested
      with the acoustic stimulus after the 5th and the 9th injections, 24 hours after
      the administration of the last dose. Audiogenic seizures were obtained in 29.4%
      of the rats tested after 5 injections and in 40.0% of the rats tested after the
      9th injection. The increased seizure susceptibility lasted 3-8 days after the
      hormone withdrawal. In conclusion, the withdrawal of high doses of progesterone
      exerts a seizure-activating effect.

PMID- 7710964
TI  - Hypertension in acute ischaemic stroke: to treat or not to treat.
AB  - The reasons for not treating hypertension could be the risk of reducing cerebral
      blood flow (CBF) which may induce additional cerebral damage in the so-called
      ischaemic "penumbra". Hypertensive patients have altered autoregulation. A severe
      hypertension (over 230/120 mmHg) may lead to further damage by cerebral edema
      which asks for antihypertensive therapy. An antihypertensive therapy was applied
      in 81 patients within the 72 hours interval from acute ischaemic stroke (AIS)
      onset. In 42 patients, the antihypertensive treatment was discontinued after the
      72-hour interval (the therapy with nifedipine in daily doses of 10-20 mg was not
      considered as hypotensive). We compared as end points: the survival, death,
      modified Rankin Scale (mRS). There were no statistically significant differences
      between end points of patients who discontinued (group C) and those who
      maintained (group T) the antihypertensive therapy. The mean value of blood
      pressure was higher in patients who maintained antihypertensive therapy (p <
      0.001 for systolic blood pressure (BP); p = 0.001593 for diastolic blood
      pressure). The mean value of age in patients in whom antihypertensive therapy was
      discontinued was higher than that found in patients who maintained
      antihypertensive therapy (p < 0.05).

PMID- 7710965
TI  - Structural modifications of intracerebral small vessels in various types of
      dementia.
AB  - Previous and recent studies stress the importance of small intracerebral vessel
      lesions in the pathogeny of some forms of dementia. The observations on this
      subject and included in our study refer to adult patients (32-86 years) selected
      only on the criterion of clinical diagnosis of dementia. To diagnose most of the
      cases, clinical experimental data and clinico-psychomotor tests were used.
      Classical neuropathological techniques were performed for the morphological study
      of their brains. All types of cerebral vessels were affected in various
      percentages by the different types of lesions. Vessel wall sclerosis of all types
      of intracerebral vessels was noticed in 50% of the cases, the thickening of the
      arteriolar wall with or without sclerosis in 25% of cases and exclusively
      capillary fibrosis in 21.4% of cases. Other types of vascular changes were
      present in a small number of cases. No correlation could be made between a
      certain type of vascular lesion and the age or diagnosis of the patient.
      Nevertheless, we could observe that wall sclerosis was more frequently found in
      groups with the oldest patients with vascular diseases (VD, MD), the thickening
      of the arteriolar wall in patients aged 60-74 years with vascular diseases, and
      capillary changes in older patients with dementia of Alzheimer type. No
      preferential location of the vascular lesions could be observed in our group of
      patients.

PMID- 7710966
TI  - Predictors of outcome in depression.
AB  - Several socio-demographic, family and clinical history variables, stressful life
      events, index episode characteristics, symptom severity, clinically and
      psychometrically assessed personality type and traits, and treatment were
      evaluated as potential predictors of multiple outcome criteria in a sample of 157
      outpatients and inpatients meeting commonly used criteria for depression
      episodes. Outcome criteria included: severity scores on the final evaluation,
      improvement rate, impairment level of functioning, clinically rated treatment
      response, episode duration and relapse frequency in one year follow-up. Gender,
      personality structure and type, stressful life event characteristics, prior
      episode number, clinical status after the last episode, symptom length at intake,
      initial symptom severity, psychotic and endogenous features emerged as
      significant predictors of depression outcome in univariate analyses. The
      combination of independent variables by multivariate regression analyses improved
      outcome prediction.

PMID- 7710967
TI  - Conservative treatment for multilocular empyema. Case report.
AB  - The case of a 35-year-old patient is reported. After a two-week interval
      following an ORL puncture in the frontal sinuses, the patient showed a
      suppuration on the right hemisphere and was admitted in the territorial
      neurosurgical clinic. Due to a progressive neurological impairment (loss of
      consciousness and left hemiplegia) the patient was transferred to the
      Neurological Clinic of "G. Marinescu" Hospital, in Bucharest. CT-scanning carried
      out in 1989, showed multiple empyemas (intrahemispheric, basal, etc.) excluding
      any surgical treatment. A conservative treatment was administered during a long
      period including antibiotics, notably cephalosporines (the third generation).
      Repetition of CT-scanning evidenced a progressive diminution of a total
      disappearance of septic intracranial collection, hence, an obvious improvement of
      the patient. After a year of treatment, the patient was considered to be
      recovered even if he still accused rare epileptic seizures, partially controlled
      by drug therapy.

PMID- 7710968
TI  - Management of the neurosurgical emergencies in pregnancy.
AB  - This study presents the files of nine pregnant women with severe neurosurgical
      diseases (traumatic, vascular, and tumoral) who were treated in the Neurosurgical
      Clinic, from 1982 to 1988. Conclusions were drawn after a survey according to the
      optimal therapy applied, to the mother or fetus priority, to the age of patients
      and to the severity of the neurological impairment. The early intervention of a
      team including the neurosurgeon, obstetrician and the specialist in the intensive
      care unit saves one life or both. A delay condemns both.

PMID- 7710969
TI  - Comparative study of the treatment with tetracyclic and tricyclic antidepressants
      in patients with minor depressive disorders.
AB  - One hundred and twenty-nine cases with depression were submitted to a comparative
      therapeutic study, using a flexible treatment administration: mianserin 30-60 mg
      and imipramine 50-150 mg. The mean dosages were 43.6 mg of mianserin and 62
      mg/day of imipramine. Twenty-nine patients were excluded from the study, the rest
      constituting 2 equal groups of 50 cases each. The study covered a period of 4
      weeks. After this period, almost 40% of the cases were discharged due to their
      obvious improvement. The significant benefits of mianserin were evident in the
      7th and in the 21st day of the study on HDRS for the total score and in the 7th
      day on HDRS for the anxiety-somatization score. The superiority of mianserin was
      also obvious due to the total score on Lipmann-Rickels' scale as well as for the
      general neurotic symptoms. No statistically significant differences between
      mianserin and imipramine for the antidepressive efficacy were observed by the end
      of the study. A greater number of secondary effects was noticed in the group
      treated with imipramine. It seems that mianserin was a better therapy for this
      category of psychic patients, especially for older cases, probably due to the
      anxiolytic influence and to a lower incidence of side-effects.

PMID- 7710970
TI  - Fractures of the peritoneal catheter of cerebrospinal fluid shunts.
AB  - A retrospective study of fractures of peritoneal catheters of
      ventriculoperitoneal shunts is described. Fracture of the peritoneal catheter
      accounts for 21.2% of shunt revisions. During the time period of January 1985
      through July 1993, 401 PS Medical peritoneal catheters were installed and 23
      fractures occurred. The fracture rate of PS Medical small-sized catheters is
      15.3%. The fracture rate of PS Medical regular-sized catheters is 2.1%. The
      overall survival rates of the PS Medical small-sized and regular-sized catheters
      are significantly statistically different (p < 0.001). The peritoneal catheters
      fractured most frequently in the neck.

PMID- 7710971
TI  - Pathogenesis of craniosynostosis.

PMID- 7710972
TI  - A case of traumatic internal carotid artery occlusion diagnosed by MRI.
AB  - The case of a 4-year-old boy with traumatic internal carotid artery occlusion is
      reported. This patient developed left upper limb monoparesis and convulsions 62 h
      after injury. Magnetic resonance imaging (MRI) showed absence of a flow void and
      a high signal in the C5 portion of the right internal carotid artery. The
      proximal side of the right carotid siphon was not demonstrated by MR angiography.
      Carotid angiography revealed occlusion of the right internal carotid artery about
      2 cm distal from the cervical carotid bifurcation. MRI appears to be useful to
      diagnose traumatic internal carotid artery occlusion, especially in children.

PMID- 7710973
TI  - Prevention of recurrent tethered spinal cord.
AB  - One of the most problematic technical considerations in surgery for the release
      of tethered spinal cord is how to prevent recurrent tethering. Recurrent
      tethering is common because the spinal canal in the baby is shallow and,
      therefore, postoperatively, the neural contents are in direct contact with the
      posterior dura. The only way to prevent a recurrent tethered cord is to be
      certain that the neural elements remain free within circumferentially patent
      cerebrospinal fluid. We hereby describe a method where a curved 1.5 mm oval piece
      of Medpor is used to create a posterior space for the neural elements. The spinal
      canal is expanded posteriorly, therefore, creating an abnormally wide canal to
      accommodate the neural elements within subarachnoid space. This methodology was
      used in 18 neonate patients, and in late tethering cases after myelomeningocele.
      Technical and theoretical considerations are discussed.

PMID- 7710974
TI  - Neurosurgical considerations on the anatomy of the medial canthus in children.
AB  - Craniofacial surgery and anterior skull base surgical techniques require an
      intimate knowledge of periorbital structures. The medial orbital anatomy is
      especially important for midline approaches to nasion encephalocele, midline
      trauma, surgery for hypertelorism as well as midline approaches to anterior skull
      base lesions. The medial canthal tendon is of primary importance in anchoring the
      eyelid medially in a cosmetic and functional fashion. This review will summarize
      the anatomic features of the medial canthus and its surrounding structures,
      including vascular and muscular components. The intimate relationship of the
      three components of the medial canthal tendon to the nasal lacrimal apparatus is
      emphasized. Techniques to prevent injury as well as to repair abnormalities in
      this area will be discussed.

PMID- 7710975
TI  - Pediatric midbrain tumors: a benign subgroup of brainstem gliomas.
AB  - The presentation, radiographic findings and course of 17 children with MRI
      documented intrinsic midbrain lesions are reviewed. The anatomic centers of all
      the lesions were tectal, peritectal, or tegmental. Lesions centered at the pineal
      gland were excluded. Signs of increased intracranial pressure from hydrocephalus
      requiring shunt placement were present in 14 patients. Histopathological
      diagnosis was confirmed in three tumors; these were low grade astrocytomas and
      all received focal irradiation, as did one unbiopsied tumor. The remaining 13
      patients with no histopathological diagnosis received no therapy other than shunt
      placement in 11. All but one of the lesions have remained clinically and
      radiographically stable, with a 4-year progression-free and total survival of 94
      and 100%, respectively. We conclude that mass lesions originating in the upper
      midbrain are a subset of intrinsic brainstem tumors with a relatively benign
      course, usually presenting with hydrocephalus after infancy. They may remain
      stable for considerable periods and may require no further therapy after
      treatment of hydrocephalus. Surgical biopsy and/or resection can usually be
      reserved for progressive or atypical lesions which may also require further
      adjuvant therapy.

PMID- 7710976
TI  - Computer tomographic scanning within 24 hours of craniotomy for a tumor in
      children.
AB  - Computed tomographic (CT) brain scans were performed without and with contrast
      enhancement within 24 h of craniotomy in 26 patients undergoing 27 operations.
      Postoperative scans were retrospectively reviewed for evidence of contrast
      enhancement, the pattern of enhancement and the presence of blood on the
      postoperative scans. Contrast enhancement was seen in the resection bed in 33% of
      patients undergoing gross total resection of their lesions, and was absent in 50%
      of patients with known residual disease. Enhancement along a corticotomy was
      present in 18% and distant meningeal enhancement was identified in 19% of
      patients. These enhancement rates were unrelated to steroid dosages, duration of
      surgery, or the interval between operation and scanning. It was not possible to
      delineate residual tumor in 63% of the patients, due to a postoperative
      enhancement pattern that stimulated enhancing vessels, the presence of
      hemorrhage, or due to the absence of calcification or preoperative enhancement.
      None of the scans were affected by technical problems (motion artifact, inability
      to complete the scan) potentially associated with scanning within 24 h of
      craniotomy. Small amounts of residual tumor remain undetectable, particularly due
      to hemorrhage in the resection bed. Although no distinct advantage in defining
      residual disease was obtained compared to scanning at 72 h, the overall rate of
      findings not related to neoplasm was slightly less for scans obtained within 24
      h.

PMID- 7710977
TI  - Tissue lactate in pediatric head trauma: a clinical study using 1H NMR
      spectroscopy.
AB  - In order to define the metabolic abnormalities associated with different types of
      pediatric head injury, proton magnetic resonance spectroscopy was performed on 21
      cerebral regions obtained from 17 patients. On the basis of MRI scans, the
      regions of interest were classified as normal (6 hemispheres), or showing diffuse
      axonal injury (3 hemispheres), contusion (4 hemispheres), or cerebral infarction
      (8 hemispheres). In comparison with normal brain there was no significant
      elevation in tissue lactate in the diffuse axonal injury patients, but a
      significant increase in the regions of contusion and infarction. It is concluded
      that treatment strategies using buffering agents are most likely to benefit these
      two groups of patients.

PMID- 7710978
TI  - Craniocervical intradural neurenteric cysts.
AB  - Neurenteric cysts are rare lesions of the central nervous system that are lined
      by epithelium of intestinal nature. They result from abnormal separation of germ
      cell layers in the 3rd week of embryonic life, leading to persistence of
      entodermal elements in the spinal canal. The common location is cervical and
      ventral to the spinal cord. The lesions have been recognized as being entodermal
      in origin by such markers as vertebral anomalies, gut cysts, bowel reduplication
      and the presence of keratin markers. Three unusual cases of childhood
      craniocervical intradural neurenteric cysts in patients aged 4-8 years are
      described. These cysts were located in the ventral aspect of the spinal canal
      ranging from the craniocervical junction to the C6 level and were associated with
      bony anomalies such as a bifid clivus, hemivertebrae and blocked vertebrae. Two
      patients presented with signs of cervical cord compression and 1 with recurrent
      meningitis. One child with an anterior cervicomedullary region mass had undergone
      unsuccessful transoral transpalatal exploration and subsequently required
      excision with a dorsolateral approach. The second patient, after two successful
      attempts at drainage via laminectomies, required myelotomy of the spinal cord to
      allow excision. Thus the patient with the lesion from C4 through C6 underwent
      vertebrectomy and anterior excision with a C4 through C7 strut graft fusion.
      There were bony and vascular anomalies which would have complicated a dorsal
      approach. Pathological diagnosis of neurenteric cysts was based on the findings
      of nonciliated mucin producing small cuboidal or columnar epithelium lining a
      cystic cavity. Neurenteric cysts are uncommon congenital anomalies which may
      become symptomatic in the pediatric population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7710979
TI  - Latex allergy in children with spina bifida.
AB  - We studied the prevalence of latex-specific IgE among the children in our
      myelomeningocele clinic and several groups of controls using skin tests, a
      commercially available ELISA and an in-house RAST. Thirty-nine of 83 (47%)
      children with myelomeningocele had antibodies directed against latex as did 6 of
      40 (15.7%) chronically ill controls, 4 of 105 (3.8%) medical controls and 2 of 75
      (2.7%) well controls. Within each study group the likelihood of a positive skin
      test increased with the number of operations the subject had undergone. Children
      with myelomeningocele were much more likely to have antibodies to latex than were
      chronically ill controls with similar surgical histories. A retrospective chart
      review of 18 years and a total of 646 operations disclosed only one episode of
      intraoperative anaphylaxis which appeared to be related to latex within our study
      group.

PMID- 7710980
TI  - Myeloma during a decade: clinical experience in a single centre.
AB  - One hundred and fifty-six patients with multiple myeloma were treated over a
      period of 12 years at St. Bartholomew's Hospital. The progress of the disease was
      affected in 96/156 patients (61%). Response was defined as achieving a plateau of
      M component. A partial or complete response was seen in 68/120 patients treated
      conventionally (56.5%), and in 28/36 patients treated with high-dose therapy
      (77.7%). The median survival of the group as a whole was 20 months, with a 2-year
      survival of just over 40%. In the 36 patients treated with high-dose therapy,
      median survival was 6 years, and in a small group who have had maintenance
      Interferon therapy, the median has not yet been reached. In a univariate
      analysis, age, intensity of therapy, haemoglobin and creatinine levels were
      significant, but multivariate analysis showed that only age and intensity of
      therapy were independent predictors for survival. The outlook for relapsed
      patients who showed progression of disease remains poor, but palliation was best
      achieved by steroid and Interferon in combination. Patients who achieve complete
      responses and are maintained on Interferon appear to be doing better both in
      terms of freedom from symptoms and in survival, and methods to enable an elderly
      population to tolerate this form of therapy need to be explored.

PMID- 7710981
TI  - Cancer vaccines try once again to live up to their promise.

PMID- 7710982
TI  - What if tamoxifen (ICI 46,474) had been found to produce rat liver tumors in
      1973? A personal perspective.

PMID- 7710983
TI  - Treatment of Waldenstrom's macroglobulinemia resistant to standard therapy with 2
      chlorodeoxyadenosine: identification of prognostic factors.
AB  - BACKGROUND: Few effective treatments are available for patients with
      Waldenstrom's macroglobulinemia that is resistant to standard therapies. We
      assessed the activity of 2-chlorodeoxyadenosine (2CdA) in patients with resistant
      macroglobulinemia in order to identify those most likely to benefit. PATIENTS AND
      METHODS: 2-chlorodeoxyadenosine was given to 46 consecutive patients with
      Waldenstrom's macroglobulinemia resistant to a combination of an alkylating agent
      and a glucocorticoid. Two courses were administered to outpatients at a dose of
      0.1 mg/kg body weight per day for a 7-day continuous infusion using a portable
      pump through a central venous catheter. Responding patients were followed without
      further therapy. RESULTS: Twenty of 46 patients responded to 2CdA therapy (43%;
      95 CI; 29 to 60%) with a significantly higher frequency of benefit among patients
      with disease relapsing off therapy (78%) or with primary resistant disease within
      the first year (57%) than in those with later phases of disease (22%). The median
      survival after treatment was 28 months and the median progression-free survival
      of responding patients was 12 months. The longest survival was measured in
      patients with primary refractory disease (projected median 36 months) and the
      shortest in those with disease in refractory relapse (median 13 months).
      CONCLUSION: 2-Chlorodeoxyadenosine is active against macroglobulinemic lymphoma
      resistant to standard regimens and most effective in patients with disease
      relapsing off treatment or during the first year of primary refractory disease.
      Little benefit was observed among patients with later phases of resistant disease
      who should receive alternative treatments.

PMID- 7710984
TI  - Serum levels of interleukin-2 receptor (CD 25) in patients with Hodgkin's
      disease, with special reference to age and prognosis.
AB  - BACKGROUND: The serum levels of soluble interleukin-2 receptor (S-sIL-2R) have
      been shown to be related to clinical outcome in Hodgkin's disease (HD). sIL-2R
      may be involved in or aggravate the immunodeficiency seen in HD patients. This
      immunodeficiency is most pronounced in elderly patients. PATIENTS AND METHODS: S
      sIL-2R was determined in 127 untreated patients with HD, diagnosed between 1979
      and 1991, in order to evaluate its prognostic value in relation to other known
      prognostic variables with special emphasis on the elderly. RESULTS: S-sIL-2R
      levels were significantly higher in patients with stages III-IV and with B
      symptoms (p < 0.001) but not in patients over 60 years of age. In multivariate
      analyses, S-sIL-2R, stage and S-orosomucoid were the most important prognostic
      factors in all patients and S-sIL-2R was the only prognostic factor in patients
      over the age of 60. CONCLUSIONS: The results indicate a future role for
      estimation of S-sIL-2R in the management of patients with HD.

PMID- 7710985
TI  - The management of chronic lymphocytic leukemia--a case history.

PMID- 7710986
TI  - A phase II trial of dacarbazine, fluorouracil and epirubicin in patients with
      neuroendocrine tumours. A study by the Italian Trials in Medical Oncology
      (I.T.M.O.) Group.
AB  - BACKGROUND: Previous experiences in the treatment of neuroendocrine tumours have
      demonstrated some activity of single agents such as adriamycin, fluorouracil
      (FU), streptozotocin and dacarbazine (DTIC). Opinions concerning the usefulness
      of polychemotherapy in carcinoid tumours are discordant, whereas better results
      have been achieved in other endocrine pancreatic neoplasms. Based on this
      background, we used multidrug chemotherapy with DTIC, FU and epirubicin in the
      treatment of different neuroendocrine tumours. METHODS: The study involved 38 pts
      with progressive and measurable disease. The treatment schedule was FU 250 mg/m2
      i.v., epirubicin 25 mg/m2 i.v., and DTIC 200 mg/m2 i.v. on days 1, 2 and 3 every
      3 weeks. RESULTS: The responses achieved by histologic types were carcinoids
      2/20, medullary thyroid carcinoma 1/7, neuroendocrine tumours 1/6; and Merkel
      cell carcinoma 3/5. The median duration of response was 5 months (range 2-11).
      Stable disease was observed in 13 cases (34%). Out of the 18 cases in
      progression, 17 had not responded to previous medical treatment. No symptom
      control was observed in 4 pts with carcinoid syndrome. Treatment toxicity was
      moderate and included nausea and vomiting, alopecia, leukopenia and mucositis.
      CONCLUSIONS: Our results document the moderate efficacy of the regimen in all of
      the histologic types. The major difference in comparison with previous studies
      was the lower response rate observed in patients with neuroendocrine tumours.

PMID- 7710987
TI  - A matched control study of familial epithelial ovarian cancer: patient
      characteristics, response to chemotherapy and outcome.
AB  - BACKGROUND: Many of the characteristics of patients with familial epithelial
      ovarian cancer (EOC) are not yet well defined. This report describes some of the
      characteristics of patients with EOC in particular response rates to chemotherapy
      and 5-year survival, and compares them with matched controls with sporadic EOC.
      PATIENTS AND METHODS: There were 28 cases of familial epithelial ovarian cancer
      (EOC) presenting to the Royal Marsden Hospital from January 1983 to September
      1993. The incidence of familial EOC over this time period was 2.2% (28/1268). For
      each case of familial EOC, 3 controls were selected and matched for age, FIGO
      stage, volume of residual disease after initial surgery and type of chemotherapy;
      the matched controls were compared to the familial EOC cases for differences in
      histological subtype, response to chemotherapy and 5-year survival. There was a
      statistically significant difference in histological subtype, 83% of patients
      with familial EOC had serous cystadenocarcinoma compared to 49% in the matched
      control group (p = 0.0025) providing evidence that familial EOC has a genetic
      basis. However there were no differences in median age or FIGO stage between
      patients with familial EOC and the sporadic cases and no difference in overall
      response to chemotherapy or 5-year survival. CONCLUSIONS: Our results imply that
      familial and sporadic EOC are biologically very similar and therefore molecular
      studies on the pathogenesis of and cellular mechanisms involved in EOC may have
      an important impact on therapeutic strategies for the much commoner sporadic form
      of the disease. In addition, our data suggest that all patients should be closely
      questioned with regard to family history not just those who present at a young
      age.

PMID- 7710988
TI  - Soft tissue sarcoma and hypercalcemia.

PMID- 7710989
TI  - Adjuvant chemo-hormonal therapy with cyclophosphamide, doxorubicin and 5
      fluorouracil (CAF) with or without medroxyprogesterone acetate for node-positive
      cancer patients. Update at 7-year follow-up.

PMID- 7710990
TI  - Gender, psychopathology, and development: from puberty to early adulthood.
AB  - We tested the hypothesis that the expression of schizophrenic psychopathology is
      dependent on the stage of adolescent development. The study had a retrospective
      design, using high-quality case-note material of cases of schizophrenia at first
      admission. Patients with onset of illness between the age of 11 and 21 years were
      included. Sexual delusions were more apparent in females (OR = 3.6;95% CI 1.6
      8.0), but otherwise no gender differences in the frequency of a range of positive
      symptoms were apparent. There was evidence that the age at which positive
      symptoms first appeared differed between males and females. The frequency of
      typical, 'first rank' schizophrenic symptoms such as auditory hallucinations,
      passivity phenomena and though interference, increased linearly with age in male
      patients, but did not vary with age in their female counterparts. The likelihood
      of displaying delusional beliefs such as persecutory delusions, explanatory
      delusions, delusions of reference and grandiose delusions increased with age in
      both sexes, but the association was stronger in males. The observation that
      typical schizophrenic symptoms in male patients are relatively uncommon during
      early adolescence, but increase as they grow older, could be explained by the
      later manifestation of puberty and associated maturational processes in boys.

PMID- 7710991
TI  - Obstetric complications and severity of illness in schizophrenia.
AB  - A history of obstetric complications (OCs) is common in schizophrenia and may
      lead to a severe form of the disorder. In order to test this possibility, three
      questions were identified: (1) Is a history of OCs in schizophrenia common in
      patients with a severe form of illness? (2) Do patients with OCs have more
      impaired function, greater severity of illness, and poorer treatment outcome than
      those with no identified OCs? (3) Are OCs associated with an early age at onset
      of illness? Obstetric history, clinical indices of functioning, and illness
      severity were obtained for 83 severely ill patients with schizophrenia. The
      proportion of patients with a history of OCs was greater in this study than has
      been reported previously. Subjects with a history of OCs had better functioning
      than those with no OCs at the time of admission but no group differences were
      found at discharge. No difference in age at onset of illness was found between
      patients with and without an OC history.

PMID- 7710992
TI  - Expressed emotion, family dynamics and symptom severity in a predictive model of
      social adjustment for schizophrenic young adults.
AB  - While numerous studies have concluded that high expressed emotion (EE) in
      relatives predicts relapse in schizophrenia, other aspects of patient outcome
      have not been well studied. Our purpose was to determine the extent to which
      family dynamics and expressed emotion may predict variance in patient social
      adjustment when controlling for symptom severity. Sixty-nine schizophrenic
      outpatients and 108 of their relatives participated. Relatives' EE was assessed,
      and they were administered the FACES III for perceptions of family cohesion and
      adaptability. Patients were interviewed at about the same time as their relatives
      and again 9 months later with the Social Adjustment Scale (SAS-II) and the BPRS.
      Between 9% and 58% of variance in each of the five SAS scales was explained by
      selected EE and family dynamics scales, while symptom severity was held constant.
      Among the results, it was found that better social adjustment in patients was
      associated with less family adaptability, and with greater emotional
      overinvolvement in relatives. Adjustment of patients in the work role was
      associated with more Critical Comments from mothers. In conclusion, some aspects
      of high EE are associated with better social adjustment in schizophrenic
      patients.

PMID- 7710993
TI  - Neuroleptic effects on neuropsychological test performance in schizophrenia.
AB  - The present study assessed the effects of neuroleptic medication on tests
      sensitive to frontal and non-frontal lobe function in schizophrenic patients. A
      test-retest design before and after initiation of neuroleptic treatment was used.
      The performance of schizophrenics was compared with that of matched normal
      controls. Schizophrenics performed more poorly than controls on most tests at
      both first and second testing. Patients' performance improved significantly
      between the test and the retest on the digit symbol subtest of the WAIS-R and on
      the Stroop 'color naming' subtest. Similarly, performance on the verbal fluency
      test and on the Rey complex figure recall tended to be better at the retest,
      although not significantly. The deficit on the Wisconsin Card Sorting Test (WCST)
      remained stable over time in patients. The result suggest that neuroleptics give
      no negative effects on cognitive functioning in schizophrenics.

PMID- 7710994
TI  - Low prevalence of age disorientation in Dutch long-stay patients.
AB  - Studies in Great-Britain and the USA have established the prevalence of 'age
      disorientation', defined as a discrepancy between true and subjective age of five
      years or more, as approximately 25% in the population of long-stay patients with
      a diagnosis of schizophrenia. We examined all schizophrenic patients in long-stay
      wards of three mental hospitals and found a prevalence of 6% (95% CI: 0.9-10.6%).
      We have no definitive explanation for this finding. 'Age disorientation' may be
      the result of an interaction between a serious form of the illness and poor
      psychosocial treatment.

PMID- 7710995
TI  - Electrical brain activity in schizophrenia described by equivalent dipoles of FFT
      data.
AB  - Since results of conventional FFT-power-analysis are reference-dependent, only
      unambiguous neurophysiological data should be used for a functional physiological
      interpretation of EEG-data. FFT-approximation with successive center-of-gravity
      dipole calculation gives unambiguous EEG-data with regard to recording reference.
      In the present investigation 22 medicated schizophrenic patients were compared
      with 22 healthy age- and sex-matched controls with regard to spontaneous resting
      EEG. More anterior and superficial equivalent-dipoles were found in the beta
      bands for schizophrenic patients compared to healthy control subjects. There was
      a tendency of increased beta-activity in schizophrenic subjects. With more severe
      schizophrenic symptoms (higher BPRS-score), the more anterior was the equivalent
      dipole localization in the beta 1-band, and the deeper in the theta-band. The
      different locations of the beta-band dipoles in schizophrenic patients suggest
      that different neuronal populations generate beta-activity in schizophrenia
      compared to healthy controls. FFT-approximation allows a substantial and
      meaningful data reduction in multichannel recordings and will hopefully help in
      understanding pathological brain functions in schizophrenia.

PMID- 7710996
TI  - Abnormal laterality in schizophrenics and their parents.
AB  - Previous studies found that schizophrenics do not show the normal right ear-left
      hemisphere perceptual advantage on language-related dichotic tests of lateralized
      cerebral function. We report evidence of a similar abnormality in non
      schizophrenic parents of schizophrenic patients. Perceptual asymmetry was first
      measured with a dichotic word test which had previously yielded differences
      between schizophrenics and controls. The parents (n = 18) demonstrated a lower
      right ear advantage (REA) than controls (n = 10) (p = 0.05), but performed
      similarly to their schizophrenic offspring (n = 10). The same subjects were given
      two additional tests. Neutral words were paired with words of a positive
      emotional valence in one test, and with words of a negative emotional valence in
      the other. On these two tests, the parents were more similar to the controls than
      to their offspring with the schizophrenics demonstrating a lower REA than their
      parents (p = 0.005) on the negative test. These results suggest that
      schizophrenics and their parents have similar abnormalities in hemispheric
      activation at baseline only, but when listening to words with negative emotional
      valence, only the schizophrenics demonstrate a further decrease in left
      hemispheric activation.

PMID- 7710997
TI  - Disturbed planum temporale asymmetry in schizophrenia. A quantitative post-mortem
      study.
AB  - The planum temporale of the temporal cortex was investigated post-mortem in 24
      schizophrenic patients and 24 age- and sex-matched control subjects.
      Schizophrenic patients demonstrated a 20% volume reduction of the left planum
      temporale (p = 0.032), whereas on the right side, there was a trend for increase
      in male schizophrenics (+22%, p = 0.17), while in female patients the volume was
      moderately decreased (-6%, p = 0.74). The mean anterior-posterior diameter of the
      planum temporale was significantly reduced in the left hemisphere (-20%, p =
      0.008), but unchanged on the right side. The asymmetry coefficients (Galaburda et
      al. (1987) Neuropsychologia 25, 853-868) for the planum temporale cortex volume
      (p = 0.02) and anterior-posterior diameter (p = 0.002) but not for mean area (p =
      0.61) were significantly different between schizophrenics and control subjects.
      These data support the idea of disturbed cerebral laterality in schizophrenia.
      The implications of methodology and patient samples are discussed.

PMID- 7710998
TI  - Correlation between left frontal phospholipids and Wisconsin Card Sort Test
      performance in schizophrenia.
AB  - The relationship between frontal lobe phospholipid measures as measured by in
      vivo 31phosphorus magnetic resonance spectroscopic imaging and performance on the
      Wisconsin Card Sort Test was examined in 16 chronic schizophrenic patients and 13
      normal controls. Lower left frontal phosphomonoester levels in the schizophrenics
      were associated with fewer categories achieved, lower percent conceptual level,
      and greater total errors. No significant correlations between frontal
      phospholipid measures and performance on the WCST were noted in the controls. The
      results suggest a relationship between altered left frontal phospholipid
      metabolism and a specific measure of frontal lobe neuropsychological functioning.

PMID- 7710999
TI  - Daily rhythmicity of temperature, pulse and blood pressure in schizophrenic
      patients.

PMID- 7711000
TI  - Histamine metabolites in cerebrospinal fluid of patients with chronic
      schizophrenia: their relationships to levels of other aminergic transmitters and
      ratings of symptoms.
AB  - Levels of the histamine metabolites, tele-methylhistamine (t-MH) and tele
      methylimidazoleacetic acid (t-MIAA), and metabolites of other aminergic
      transmitters and of norepinephrine were measured in cerebrospinal fluid of 36
      inpatients with chronic schizophrenia and eight controls. The mean t-MH level
      from controls was nearly identical to the levels seen previously in healthy
      volunteers. Compared with controls, the mean level of t-MH in the schizophrenic
      patients was 2.6-fold higher (p = 0.006); 21 of the patients had levels exceeding
      the range of controls. There was no significant difference (p > 0.05) in levels
      of other analytes, although the levels of t-MH correlated significantly with
      those of t-MIAA, homovanillic acid, 3,4-dihydroxyphenylacetic acid,
      norepinephrine, 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid.
      The difference in levels of t-MH were not attributable to medication, since those
      taking (n = 10) or withdrawn from (n = 26) neuroleptic drugs had nearly the same
      mean levels of t-MH; each group had higher levels than controls (ANOVA: p <
      0.05). Patients with or without tardive dyskinesia showed no significant
      differences in means of any analyte. Only levels of t-MH among those with
      schizophrenia correlated with positive symptom scores on the Psychiatric Symptom
      Assessment Scale (rs = 0.45, p < 0.02). The elevated levels of t-MH in
      cerebrospinal fluid, which represent histamine that was released and metabolized,
      suggest increased central histaminergic activity in patients with chronic
      schizophrenia.

PMID- 7711001
TI  - British Society for Histocompatibility and Immunogenetics and European Foundation
      for Immunogenetics joint meeting. Brighton, 8-11 March 1995. Abstracts.

PMID- 7711002
TI  - Pathophysiological principles of the relation between myocardial hypertrophy of
      the left ventricle and its regression.
AB  - Hypertrophy of the left heart ventricle as a consequence of a haemodynamic
      overload is a process of ambiguous biological value. Although hypertrophy allows
      to increase the performance of the ventricle without substantial elevation in
      wall tension, it represents a risk factor of cardiac morbidity and mortality. The
      regression of hypertrophy seems to be a rational outcome of this ambivalent
      situation. Not every reversal of hypertrophied muscle mass, however, can be
      unambiguously considered therapeutic success. The biological value of hypertrophy
      regression depends on the type of hypertrophy, on the level of deterioration of
      the heart by a long-lasting haemodynamic overload, as well as on the way in which
      the reversal of hypertrophy is achieved. Even in the case when functional
      characteristics are preserved or even improved compared to the hypertrophied
      heart, hypertrophy regression need not automatically mean a decrease of the
      cardiovascular risk induced by ventricular hypertrophy. Regression of hypertrophy
      may be even disadvantageous in those situations when reduction of hypertrophy and
      reduction of the haemodynamic overload proceed in a disproportional manner.
      Spontaneously developing regression of the hypertrophied left ventricle as
      demonstrated on the model of aortal insufficiency, is an explicitly pathological
      state, resulting in heart failure. Regression of myocardial hypertrophy should
      not be considered the primary therapeutic aim but rather a part of the management
      of haemodynamic overload of the heart. The main aim is to achieve optimal
      perfusion of the periphery, yet at the same time to provide such conditions which
      would prevent the working load of the heart to become a limiting factor of
      survival.

PMID- 7711003
TI  - Preservation of rabbit hearts with different cardioplegic solutions at low
      temperature.
AB  - An organ-preserving solution, including in its composition also organic
      molecules, prepared at the University of Wisconsin (UW), has been successfully
      used for preservation of liver, pancreas and kidney, and has recently been tested
      for long-term storage of isolated hearts. We have compared the effectiveness of
      the UW solution with that of a standard crystalloid cardioplegic solution (St.
      Thomas, ST) in the functional and structural preservation of isolated hearts. The
      hearts taken from 24 rabbits were mounted on a Langendorff preparation. After
      assessment of the left ventricular function by an intraventricular balloon, 40 ml
      of either cardioplegic solution were injected to arrest the hearts (12 UW and 12
      ST), which were then immersed in the same solution for 4 h at 4 degrees C without
      perfusion. After this period, the hearts were normothermally reperfused with
      oxygenated Krebs-Henseleit solution for 30 min, and finally left ventricular
      function was assessed again. An electron microscopic evaluation was performed as
      well. Significantly higher recovery of left ventricular developed pressure (p <
      0.01) and of negative dP/dt (p < 0.05), was observed after preservation with UW,
      while no difference on positive dP/dt was found. After reperfusion, left
      ventricular end-diastolic pressure significantly rose with ST (p < 0.01), but did
      not change with UW; the difference between ST and UW was significant (p < 0.01).
      Tissue water content was significantly lower in the hearts preserved with UW (p <
      0.05). Electron microscopic examination revealed generally good preservation with
      no substantial difference between the two solutions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7711004
TI  - Partially phosphorylated phosphorylase in the rat heart after beta-receptor
      stimulation in vivo.
AB  - The formation of the phosphorylase ab hybrid and its further transformation into
      phosphorylase a has been demonstrated in the rat heart after different periods of
      i.v. isoproterenol administration. Phosphorylase ab hybrid was determined in the
      presence of AMP and/or caffeine. Only the partially phosphorylated phosphorylase
      was found in the control rat hearts and its activity was 30% of the total
      phosphorylase. The phosphorylase ab hybrid was disclosed particularly after small
      isoproterenol doses (0.031-0.062 microgram.kg-1) and at short time interval (15
      s) after its administration. Higher isoproterenol doses (0.25-0.5 microgram.kg-1)
      changed the partially phosphorylated phosphorylase to phosphorylase a (58%) after
      a longer time interval (40 s). The phosphorylase ab hybrid was revealed even at
      the maximal rate of stimulation. The formation of the phosphorylase ab hybrid in
      the rat heart in vivo appears to be of physiological significance. Our results
      confirmed the earlier suggestion that the -AMP/+AMP activity ratio reflects the
      percentage proportion of the phosphorylated subunits of phosphorylase but not of
      the activated phosphorylase molecules.

PMID- 7711005
TI  - Changes of insulin and glucagon binding to receptors in hepatocytes during liver
      regeneration.
AB  - The binding of insulin (INS) and glucagon (GL) on isolated rat hepatocytes during
      the process of liver regeneration after partial hepatectomy was determined. Adult
      male rats were subjected to 65-70% partial hepatectomy, control animals were sham
      operated. The binding of radioiodine labelled INS and GL to isolated hepatocytes
      was determined 1, 2, 3 and 5 days after the surgery. The plasma levels of INS and
      glucose and microviscosity of liver plasma membranes were also measured. The
      decrease of INS receptor binding capacity was found 1, 2, and 3 days after
      operation. No differences in sham and partially hepatectomized groups in INS
      binding were noted 5 days after operation. A single insulin injection during the
      process of regeneration did not affect these changes of INS binding to
      hepatocytes. The increase of GL binding was observed on the third day after
      partial hepatectomy, however, on the 5th day no changes of GL binding to its
      receptors were noted. The plasma insulin and glucose levels were similar in both
      hepatectomized and sham-operated rats. The increase of plasma membrane
      microviscosity of hepatocytes during the process of liver regeneration and a
      negative correlation between INS binding and membrane microviscosity were found.
      These results demonstrated significant changes in binding parameters of both INS
      and GL receptors in hepatocytes during liver regeneration induced by partial
      hepatectomy.

PMID- 7711006
TI  - Changes in beta-adrenergic receptors in the neurohypophysis and intermediate lobe
      of rat hypophysis exposed to stress.
AB  - Changes in beta-adrenergic receptors in the neurohypophysis and intermediate lobe
      of the rat have been characterized under physiological and stress conditions.
      Classical immobilization stress (IMO) was also combined with the immersion of
      rats into water (IMO + COLD stress). Both types of stress were applied for 30, 60
      or 150 min. The intensity of stress stimuli were controlled by measuring the
      level of plasma ACTH. Changes in the level of plasma ACTH indicate that both
      types of experimental protocol induced reliable and reproducible stress
      conditions. Binding studies dealing with beta-adrenergic receptors in the
      intermediate lobe and neurohypophysis were performed in saturation binding
      studies by using of 125I-iodopindolol. Binding parameters, maximal binding
      capacity (Bmax) and dissociation constant (Kd) were assessed by nonlinear
      analysis with computer program Viewfit. In the neurohypophysis, no changes of Kd
      were found in the stressed animals. However, maximal binding capacity was
      decreased significantly with the increased exposure to the stress. In the
      intermediate lobe Kd values were slightly decreased and Bmax values decreased
      gradually with increasing duration of stress exposure. Our findings suggest that
      the process of receptor desensitization of beta-adrenergic receptors can also be
      detected under stress conditions in the neurohypophysis and intermediate lobe of
      the pituitary gland where it could contribute to the mechanisms involved in
      stress reactions.

PMID- 7711007
TI  - Glucose administration does not modulate prolactin response to exercise, TRH or
      haloperidol injection.
AB  - Glucose was found to exert an In vitro regulatory effect on prolactin secretion.
      Its role in the modulation of stimulated secretion of prolactin in man is,
      however, not clear. To evaluate the effect of hyperglycaemia on prolactin
      release, three stimulatory tests with different mechanisms of stimulation were
      employed. Healthy male subjects served as volunteers during submaximal exercise,
      TRH test (0.2 mg i.v.) and administration of haloperidol (2 mg i.v.). Glucose
      (100 g in 400 ml) or an equal volume of water was given 30 min before the tests.
      Blood for glucose and prolactin analysis was taken via an indwelling catheter.
      The plasma prolactin concentration increased in response to each of the stimuli
      applied. However, the prolactin increase during hyperglycaemia did not differ
      from values obtained in tests performed in normoglycaemia after water
      administration. These results indicate that prolactin release in healthy man is
      not modulated by hyperglycaemia.

PMID- 7711008
TI  - Terguride but not bromocriptine alleviated glucose tolerance abnormalities and
      hyperlipidaemia in obese and lean genetically hypertensive Koletsky rats.
AB  - Glucose tolerance, total plasma cholesterol and plasma triglycerides were studied
      in the genetically hypertensive obese Koletsky rats (SHR/N-cp) and in their lean
      siblings. The initial part of the glucose tolerance curve was substantially
      elevated in both obese and lean Koletsky animals compared to normotensive Wistar
      rats. The abnormal glucose tolerance in hypertensive rats was accompanied by
      increased total plasma cholesterol and plasma triglycerides. Long-term treatment
      with dopaminergic agonists terguride or bromocriptine (0.2 and 2.0 mg/kg/day,
      respectively) exerted similar effects on lipid metabolism but both drugs differed
      in their influence on glucose tolerance. Terguride lowered plasma lipids and
      normalized glucose tolerance in both obese and lean Koletsky rats. Bromocriptine
      reduced hyperlipidaemia but did not attenuate the abnormalities of glucose
      tolerance in either lean or obese Koletsky animals.

PMID- 7711009
TI  - Interactions between hepatic ascorbic acid, cytochrome P-450 and lipids in female
      guinea pigs with different ascorbic acid intake.
AB  - Changes in serum and liver lipids, hepatic ascorbic acid (AA) and cytochrome P
      450 were investigated in female guinea pigs divided into three groups with
      different AA intake in drinking water (10, 100 and 1000 mg AA per liter) for 10
      weeks. Serum and liver total cholesterol significantly decreased in guinea pigs
      receiving 100 and 1000 mg AA per liter of drinking water when compared with
      guinea pigs with suboptimal AA intake (10 mg/l). Similarly, serum triglycerides
      were decreased in the groups with higher AA intake. Liver AA concentration
      increased significantly in accordance with rising AA doses. High AA intake (1000
      mg/l) for 10 weeks resulted in significant increase of both cytochromes P-450 and
      cytochrome b5 and total haeme content in liver microsomes when compared to guinea
      pigs with suboptimal AA intake. A significant positive correlation between
      hepatic AA concentration and cytochrome P-450 content was observed. A close
      negative correlation between liver total cholesterol and cytochrome P-450 content
      in hepatic microsomes was also seen. Long-term suboptimal AA intake may
      unfavourably alter the blood and liver lipid profile as well as the capacity of
      hepatic drug metabolizing enzymes in both male and female guinea pigs.

PMID- 7711010
TI  - Effects of MK-801 (dizocilpine) and ketamine on strychnine-induced convulsions in
      rats: comparison with benzodiazepines and standard anticonvulsants.
AB  - The effects of two non-competitive NMDA antagonists--MK-801 and ketamine--were
      studied in a model of generalized seizures elicited by s.c. injection of
      strychnine (2 or 3 mg/kg) in adult rats. The animals were observed in isolation
      for 30 min after strychnine administration. Pretreatment with MK-801 (0.5 or 2
      mg/kg i.p.) suppressed the tonic, but not the clonic phase of generalized
      seizures following both doses of strychnine. A similar action of ketamine (20 or
      40 mg/kg i.p.) was indicated but it did not attain statistical significance.
      Strychnine-induced lethality was not changed significantly. A comparison with
      antiepileptic drugs demonstrated that only phenobarbital (10-80 mg/kg i.p.) was
      clearly effective against strychnine-induced seizures; carbamazepine (25 or 50
      mg/kg i.p.) and partly phenytoin (30 or 60 mg/kg i.p.) were able to suppress the
      incidence of the tonic phase. Primidone (40 or 80 mg/kg i.p.) as well as the
      benzodiazpines bretazenil (0.1 or 1 mg/kg i.p.) and midazolam (two lower doses of
      0.5 and 1 mg/kg i.p.) were without significant effect. The 2 mg/kg dose of
      midazolam was partly effective. Only phenobarbital, carbamazepine and the highest
      dose of midazolam prevented strychnine-induced lethality.

PMID- 7711011
TI  - Effects of electroconvulsive shock on catecholamine release in the corpus
      striatum of the rat: a voltammetric study.
AB  - A voltammetric technique was used (differential pulse voltammetry with a carbon
      fibre microelectrode) to investigate dynamics of the changes of catecholamine
      overflow in the corpus striatum following electroconvulsive stimulation (ECS) of
      chloral hydrate-anaesthetized rats. Application of "maximal" ECS (50 Hz, AC, sine
      wave, approximately 150 mA, 0.2 s) caused large enhancement of catechol-oxidative
      current (CA.OC): In the first minute after its arrest, the CA.OC peak raised to
      1032 +/- 405% (n = 5, mean +/- S.D.) of the controls (P < or = 0.001, Student's t
      test). This large elevation of the extracellular catecholamine content ceased
      rapidly--the baseline level was attained in the second minute. CA.OC changes
      evoked by a "minimal" ECS (50 Hz, AC, sine wave, approximately 30 mA, 0.2 s) were
      equivocal in the first minute (increase, decrease: 145 +/- 56%, P > 0.05, n = 6).
      Possible mechanisms of the ECS therapeutic effect are discussed.

PMID- 7711012
TI  - Evidence for a molten globule-like transition state in protein folding from
      determination of activation volumes.
AB  - One of the most important, yet elusive, aspects of the protein folding question
      lies in the nature of the transition state. Direct information about the
      structural properties of the transition state can be obtained from determination
      of the activation volumes for the folding and unfolding transitions. The present
      pressure-jump relaxation study on the folding/unfolding of staphylococcal
      nuclease reveals that the volume of the protein-solvent system is larger in the
      transition state than in either the folded or unfolded states. Moreover, the
      activation volume of folding is much larger than that of unfolding. These results
      support a molten globule-like model for the transition state of nuclease in which
      the polypeptide chain is in a collapsed, loosely packed, solvent-excluded
      structure. In this model, hydrophobic collapse with concomitant desolvation is
      the rate-limiting step in the folding of the polypeptide chain, and solvent
      excluded expansion of the folded state is the rate-limiting step in protein
      unfolding.

PMID- 7711013
TI  - Purification, characterization, synthesis, and cloning of the lockjaw peptide
      from Conus purpurascens venom.
AB  - The major groups of Conus peptides previously characterized from fish-hunting
      cone snail venoms (the alpha-, mu-, and omega-conotoxins) all blocked
      neuromuscular transmission. A novel activity, the "lockjaw peptide", from the
      fish-hunting Conus purpurascens, caused a rigid (instead of flaccid) paralysis in
      fish and increased excitability at the neuromuscular junction (instead of a
      block). We report the purification, biological activity, biochemical and
      preliminary physiological characterization, and chemical synthesis of the lockjaw
      peptide and the sequence of a cDNA clone encoding its precursor. Taken together,
      the data lead us to conclude that the lockjaw peptide is a vertebrate-specific
      delta-conotoxin, which targets voltage-sensitive sodium channels. The sequence of
      the peptide, which we designate delta-conotoxin PVIA, is (O = 4-trans
      hydroxyproline) EACYAOGTFCGIKOGLCCSEFCLPGVCFG-NH2. This is the first of a diverse
      spectrum of Conus peptides which are excitotoxins in vertebrate systems.

PMID- 7711014
TI  - Hepatitis core antigen produced in Escherichia coli: subunit composition,
      conformational analysis, and in vitro capsid assembly.
AB  - The production and biochemical and physiocochemical analysis are described of
      recombinant-produced hepatitis B virus core antigen (HBcAg capsid) and the
      corresponding particle produced by a deletion mutant missing the C-terminal 39
      residues (HBeAg). Conditions for producing HBeAg from HBcAg capsids by in vitro
      proteolysis are also described. The morphology and masses of these capsids were
      determined by scanning transmission electron microscopy. Both HBcAg and HBeAg
      capsids comprise two size classes that correspond to icosahedral lattices with
      triangulation numbers (T) of 3 and 4, containing 180 and 240 subunits per capsid,
      respectively. This dimorphism was confirmed by sedimentation equilibrium and
      sedimentation velocity measurements on a Beckman Optima XL-A analytical
      ultracentrifuge. More than 60% of HBcAg capsids were T = 4, whereas only 15-20%
      of HBeAg capsids were of this size class: the remainder, in each case, were T =
      3. Circular dichroism and Raman spectroscopy were used to determine the overall
      secondary structures of HBcAg and HBeAg capsids. Both have high alpha-helical
      contents, implying that this capsid protein does not conform to the canonical
      beta-barrel motif seen for all plant and animal icosahedral viral capsids solved
      to date. We suggest that the C-terminal domain of HBcAg has a random coil
      conformation. In vitro dissociation of HBeAg capsids under relatively mild
      conditions yielded stable dimers. The reassociation of HBeAg dimers into capsids
      appears to be driven by hydrophobic processes at neutral pH. Capsid assembly is
      accompanied by little change in subunit conformation as judged by circular
      dichroism and fluorescence spectroscopy. The thermal stability of HBcAg capsids
      was compared calorimetrically with that of in vitro assembled HBeAg capsids. Both
      have melting temperatures > 90 degrees C, implying that the C-terminal region
      makes little difference to the thermal stability of HBcAg: nevertheless, we
      discuss its possible role in facilitating disassembly and the release of viral
      nucleic acid.

PMID- 7711015
TI  - X-ray crystal structure of the soybean agglutinin cross-linked with a biantennary
      analog of the blood group I carbohydrate antigen.
AB  - Soybean agglutinin (SBA) (Glycine max), which is a tetrameric GalNAc/Gal-specific
      lectin, has recently been reported to form unique, highly organized cross-linked
      complexes with a series of naturally occurring and synthetic multiantennary
      carbohydrates with terminal GalNAc or Gal residues [Gupta, D., Bhattacharyya, L.,
      Fant, J., Macaluso, F., Sabesan, S., & Brewer, C. F. (1994) Biochemistry 33, 7495
      7504]. In order to elucidate the nature of these complexes, the X-ray
      crystallographic structure of SBA cross-linked with a biantennary analog of the
      blood group I carbohydrate antigen is reported. The structure reveals that
      lattice formation is promoted uniquely by the bridging action of the bivalent
      pentasaccharide (beta-LacNAc)2Gal-beta-R, where R is -O(CH2)5COOCH3 and the beta
      LacNAc moieties are linked to the 2 and 6 positions of the core Gal. The
      structure of SBA complexed with the synthetic biantennary pentasaccharide has
      thus been determined by molecular replacement techniques and refined at 2.6 A
      resolution to an R value of 20.1%. The crystals are hexagonal with a P6(4)22
      space group, which differs significantly from that of crystals of the free
      protein. In the structure, each monomeric asymmetric unit contains a Man9
      oligomannose-type chain at Asn 75, with only the first two GlcNAc residues
      visible. The overall tertiary structure of the SBA subunit is similar to that of
      other legume lectins as well as certain animal lectins. However, the dimer
      interface in the SBA tetramer is unusual in that only one complete peptide chain
      is sterically permitted, thus requiring juxtapositioning of one C-terminal
      fragmented subunit together with an intact subunit. Association between SBA
      tetramers involves binding of the terminal Gal residues of the pentasaccharide at
      identical sites in each monomer, with the sugar cross-linking to a symmetry
      related neighbor molecule. The cross-linking pentasaccharide is in a conformation
      that possesses a pseudo-2-fold axis of symmetry which lies on a crystallographic
      2-fold axis of symmetry of the lattice. Hence, the symmetry properties of the
      bivalent oligosaccharide as well as the lectin are structural determinants of the
      lattice. The results are discussed in terms of multidimensional carbohydrate
      lectin cross-linked complexes, as well as the signal transduction properties of
      multivalent lectins.

PMID- 7711016
TI  - Conformation of micellar phospholipid bound to the active site of phospholipase
      A2.
AB  - Transferred NOE techniques have been used to determine the structure of
      phospholipid analogues bound to the active site of cobra venom phospholipase A2
      (PLA2). These experiments were carried out on PLA2 with a substrate analogue
      which serves as an inhibitor, 1-(hexylthio)-2-(nonanoylamino)-1,2-dideoxy-sn
      glycero-3-pho sphocholine (PC9). Because this inhibitor binds tightly to the
      enzyme and forms micelles at millimolar concentrations, experiments could be
      carried out to determine the conformation of the inhibitor when bound to the
      enzyme at the lipid-water interface. NOEs of the micellar lipid develop
      inefficiently in the absence of enzyme. NOESY experiments in the presence of PLA2
      were used to determine the inhibitor structure and conformation when bound to the
      enzyme. The inhibitor adopts an active site conformation in which the end of the
      sn-2 chain is within 5 A of the alpha-methylene protons of the sn-1 chain.
      However, NOE cross-peaks in the experiments indicate that the backbone
      conformation of the bound lipid is different from that of a shorter chain lipid
      which forms monomers [Plesniak et al. (1993) Biochemistry 32, 5009-5016].

PMID- 7711017
TI  - S-prenylated cysteine analogues inhibit receptor-mediated G protein activation in
      native human granulocyte and reconstituted bovine retinal rod outer segment
      membranes.
AB  - We have previously shown that the S-prenylated cysteine analogue N-acetyl-S
      trans,trans-farnesyl-L-cysteine (L-AFC) inhibits basal and formyl peptide
      receptor-stimulated binding of guanosine 5'-O-(3-thiotriphosphate) (GTP[S]) to
      and hydrolysis of GTP by membranes of HL-60 granulocytes and have presented
      evidence suggesting that this inhibition was not caused by reduced protein
      carboxyl methylation [Scheer, A., & Gierschik, P. (1993) FEBS Lett. 319, 110
      114]. We now report a detailed analysis of the structural properties of S
      prenylated cysteine analogues required for this inhibition and demonstrate that S
      prenylcysteines also suppress basal and receptor-stimulated GTP[S] binding to
      human peripheral neutrophil and HL-60 granulocyte membranes when stimulated by
      formyl peptide and complement C5a, respectively. S-Prenylcysteines did not affect
      pertussis toxin-mediated [32P]ADP-ribosylation of Gi proteins. The inhibitory
      effect of L-AFC was reversible and was not mimicked by farnesylic acid. L-AFC
      also interfered with GTP[S] binding to retinal transducin when stimulated by
      light-activated rhodopsin in a reconstituted system. This inhibitory effect was
      fully reversed upon increasing the concentration of either the G protein beta
      gamma dimer or the activated receptor. On the basis of these results, we suggest
      that S-prenylated cysteine analogues like L-AFC inhibit receptor-mediated G
      protein activation by specifically and reversibly interfering with the
      interaction of activated receptors with G proteins, most likely with their beta
      gamma dimers, rather than by inhibiting alpha.beta gamma heterotrimer formation.

PMID- 7711018
TI  - Comparison of the signaling abilities of the Drosophila and human insulin
      receptors in mammalian cells.
AB  - Chimeric receptors encoding either the whole or a portion of the cytoplasmic
      domain of the drosophila insulin receptor (IR) with the extracellular domain of
      the human IR were expressed either transiently in COS cells or stably in Chinese
      hamster ovary cells and compared with the wild-type human IR. All three receptors
      bound insulin equally and exhibited an insulin-activated tyrosine kinase
      activity. The ability of the drosophila cytoplasmic domain to mediate the
      tyrosine phosphorylation of insulin receptor substrate 1, stimulate cell
      proliferation, and activate MAP kinase was found to be indistinguishable from
      that of the human IR. The chimeric drosophila receptors did not bind more
      phosphatidylinositol 3-kinase than the human IR, despite containing a C-terminal
      extension with potential tyrosine phosphorylation sites in the motif recognized
      by the SH2 domain of this enzyme. Thus, the essential signal-transducing
      abilities of the IR appear to have been conserved from invertebrates to mammals,
      despite the considerable differences in the sequences of these receptors.

PMID- 7711019
TI  - Structure and dynamics of a DNA.RNA hybrid duplex with a chiral phosphorothioate
      moiety: NMR and molecular dynamics with conventional and time-averaged
      restraints.
AB  - The three-dimensional structure of two thiophosphate-modified DNA.RNA hybrid
      duplexes d(GCTATAApsTGG).r(CCAUUAUAGC), one with R-thiophosphate chirality and
      one with S-thiophosphate chirality, have been determined by restrained molecular
      dynamics simulations (rMD). As the two yielded almost identical results, a
      description of results can be presented in the singular. The conformational
      flexibility of this hybrid has been investigated by employing time-averaged
      constraints during the molecular dynamics simulations (MD-tar). A set of
      structural restraints, comprising 322 precise interproton distance constraints
      obtained by a complete relaxation matrix analysis of the 2D NOE intensities as
      well as J coupling constants obtained from quantitative simulations of DQF-COSY
      cross-peaks in deoxyriboses, was reported in our previous paper [Gonzalez, C.,
      Stec, W., Kobylanska, A., Hogrefe, R. I., Reynolds, M., & James, T. L. (1994)
      Biochemistry 33, 11062-11072]. Multiple conformations of the deoxyribose moieties
      were evident from the scalar coupling constant analysis. Accurate distance
      constraints, obtained from complete relaxation matrix analysis, yielded a time
      averaged solution structure via conventional restrained molecular dynamics which
      is not compatible with the experimental J coupling constants (root-mean-square
      deviation in J value approximately 2 Hz). However, vicinal coupling constant
      information can be reproduced when time-averaged constraints are used during the
      molecular dynamics calculations instead of the conventional restraints (Jrms
      approximately 0.6 Hz). MD-tar simulations also improve the NMR R factors. This
      improvement is more evident in the DNA than in the RNA strand, where no
      indication of conformational flexibility had been obtained. Analysis of the MD
      tar trajectories confirms that deoxyriboses undergo pucker transitions between
      the S and N domain, with the major conformer in the S domain. The ribose moieties
      in the RNA strand, however, remain in the N domain during the entire simulation.
      Conformations of deoxyriboses in the intermediate domain near O4'-endo are
      obtained when the average structure is calculated with conventional NMR
      restraints. Since these conformations cannot account for the experimental J
      coupling information, and they only appear in a very low population in the MD-tar
      ensemble, we conclude that intermediate E sugar puckers are artifacts produced by
      the attempt to fit all the structural constraints simultaneously when in reality
      more than one conformer is present. Most structural features of the duplex remain
      the same in the average structure and in the MD-tar ensemble, e.g., the minor
      groove width, exhibiting an intermediate value compared with those of canonical A
      and B-like structures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711020
TI  - Refinement of netropsin bound to DNA: bias and feedback in electron density map
      interpretation.
AB  - The X-ray crystal structure of the complex of the B-DNA dodecamer CGCGAATTCGCG
      with the antitumor drug netropsin has been reexamined to locate the drug
      accurately for computer-based drug design. The optimum solution is with the drug
      centered in the AATT region of the minor groove, making three good bifurcated
      hydrogen bonds with adenine N3 and thymine O2 atoms along the floor of the
      groove. Pyrrole rings of netropsin are packed against the C2 positions of
      adenines, leaving no room for the amine group of guanine and, hence, providing a
      structural rationale for the A.T specificity of netropsin. An alternative
      positioning in which the drug is shifted along the minor groove by ca. one-half
      base pair step is rejected on the basis of free R factor calculations and the
      appearance of the original drug-free difference maps. Final omit maps, although
      of more pleasing appearance, are not a dependable means of discriminating between
      right and wrong structures. The shifted alternative drug position ignores
      potential hydrogen bonding along the floor of the groove, provides no explanation
      for netropsin's observed A.T specificity, and is contradicted by NMR results
      [Patel, D. J. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 6424].

PMID- 7711021
TI  - Properties of the 5'-->3' exonuclease/ribonuclease H activity of Thermus
      thermophilus DNA polymerase.
AB  - The recombinant 94 kDa Thermus thermophilus DNA polymerase (rTth pol) was found
      to release [33P]UMP when incubated with a RNA.DNA hybrid containing a [33P]UMP
      labeled RNA strand. The RNase H activity was optimally active in the presence of
      low monovalent salt concentrations and when Mn2+ was used as the divalent cation
      activator. RNase H activity also was observed when Mg2+ replaced the Mn2+, but to
      a much lesser extent. A 60 nucleotide long, 5'- or 3'-radiolabeled RNA or DNA
      oligomer hybridized to a complementary DNA oligomer was used to determine the
      mode of digestion. The radiolabeled RNA.DNA hybrid or DNA.DNA duplex was
      incubated with rTth pol using various metal ion conditions and different
      incubation times. The DNA.DNA duplex showed very little enzymatic cleavage by
      rTth pol regardless of the Mn2+ or Mg2+ concentration. However, nearly complete
      digestion of the RNA.DNA hybrid was observed over a wide Mn2+ concentration
      range, thus demonstrating a preferential degradation of the RNA.DNA hybrid vs the
      DNA.DNA duplex. Time course reactions of the enzymatic digestion of the 3'
      labeled RNA.DNA hybrid or DNA.DNA duplex by rTth pol indicated that digestion of
      the substrates occurred exonucleolytically in the 5'-->3' direction.

PMID- 7711022
TI  - DNA polymerase delta holoenzyme: action on single-stranded DNA and on double
      stranded DNA in the presence of replicative DNA helicases.
AB  - DNA polymerase delta requires proliferating cell nuclear antigen and replication
      factor C to form a holoenzyme efficient in DNA synthesis. We have analyzed three
      different aspects of calf thymus DNA polymerase delta holoenzyme: (i) analysis of
      pausing during DNA synthesis, (ii) replication of double-stranded DNA in the
      absence of additional factors, and (iii) replication of double-stranded DNA in
      the presence of the two known replicative DNA helicases from simian virus 40 and
      bovine papilloma virus. DNA polymerase delta holoenzyme replicated primed single
      stranded DNA at a rate of 100-300 nucleotides/min, partially overcoming multiple
      pause sites on DNA. While Escherichia coli single-strand DNA binding protein
      helped DNA polymerase delta pass through pause sites, the DNA polymerase delta
      itself appeared to dissociate from the template in the absence of synthesis or
      when encountering pause sites. Proliferating cell nuclear antigen likely remained
      on the template. DNA polymerase delta holoenzyme could perform limited strand
      displacement synthesis on double-stranded gapped circular DNA, and this reaction
      was not stimulated either by replication protein A or by E. coli single-strand
      DNA binding protein. DNA polymerase delta holoenzyme could efficiently cooperate
      with replicative DNA helicases from simian virus 40 (large T antigen) and bovine
      papilloma virus 1 (protein E1) in replication through double-stranded DNA in a
      reaction that required replication protein A or E. coli single-strand DNA binding
      protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711023
TI  - Nucleotide excision repair DNA synthesis by DNA polymerase epsilon in the
      presence of PCNA, RFC, and RPA.
AB  - In eukaryotes, nucleotide excision repair of DNA is a complex process that
      requires many polypeptides to perform dual incision and remove a segment of about
      30 nucleotides containing the damage, followed by repair DNA synthesis to replace
      the excised segment. Nucleotide excision repair DNA synthesis is dependent on
      proliferating cell nuclear antigen (PCNA). To study gap-filling DNA synthesis
      during DNA nucleotide excision repair, UV-damaged DNA was first incubated with
      PCNA-depleted human cell extracts to create repair incisions. Purified DNA
      polymerase delta or epsilon, with DNA ligase, was then used to form the repair
      patch. DNA polymerase delta could perform repair synthesis and was strictly
      dependent on the presence of both PCNA and replication factor C, but gave rise to
      a very low proportion of complete, ligated circles. The presence of replication
      protein A (which is also required for nucleotide excision repair) did not alter
      this result, while addition of DNase IV increased the fraction of ligated
      products. DNA polymerase epsilon, on the other hand, could fill the repair patch
      in the absence of PCNA and replication factor C, and most of the products were
      ligated circles. Addition of replication protein A changed the situation
      dramatically, and synthesis by polymerase epsilon became dependent on both PCNA
      and replication factor C. A combination of DNA polymerase epsilon, PCNA,
      replication factor C, replication protein A, and DNA ligase I appears to be well
      suited to the task of creating nucleotide excision repair patches.

PMID- 7711024
TI  - Analysis of the role of the KMSKS loop in the catalytic mechanism of the tyrosyl
      tRNA synthetase using multimutant cycles.
AB  - A mobile loop in tyrosyl-tRNA synthetase, which corresponds to the KMSKS
      signature sequence of class I aminoacyl-tRNA synthetases, destabilizes the
      E.Tyr.ATP complex but stabilizes the following E.[Tyr-ATP]not equal to transition
      state for the formation of E.Tyr-AMP. Three amino acid residues in the mobile
      loop, K230, K233, and T234, are known to be primarily responsible for these
      effects. We now analyze the network of interactions between these three amino
      acids using multiple mutant free energy cycles. The complete characterization of
      the coupling energies within the mobile loop allows each of the steps leading to
      the formation of the transition state complex to be dissected into its energetic
      components. In particular, it is found that, in the absence of a functional
      mobile loop, there is synergistic coupling between the tyrosine and ATP
      substrates (i.e., each enhances the binding affinity of the other) which
      stabilizes the E.Tyr.ATP intermediate preceding the transition state complex.
      Thus, the mobile loop disrupts the synergism between the ATP and tyrosine
      substrates, using the ATP binding energy to stabilize the transition state for
      the reaction. Whereas the net effect of the mobile loop in the E.Tyr.ATP complex
      results from several conflicting side chain interactions that tend to offset each
      other, conflicting interactions in the E.[Tyr-ATP]not equal to transition state
      complex have been minimized and stabilizing pairwise interactions between the
      K230, K233, and T234 side chains are optimized. The tight coupling between the
      side chains of K230, K233, and T234 suggests that the mobile loop adopts a highly
      constrained conformation during formation of the transition state complex. These
      results quantitatively demonstrate the importance of side chain interactions in
      enzyme catalysis and illustrate the use of binding energy to stabilize the
      transition state of a reaction and the presence of unfavorable interactions to
      destabilize the ground state.

PMID- 7711025
TI  - Altering the regiospecificity of androstenedione hydroxylase activity in P450s 2a
      4/5 by a mutation of the residue at position 481.
AB  - Mouse P450 2a-5 (coumarin 7-hydroxylase) acquires androstenedione (AD)
      hydroxylase activity by substituting Phe at position 209 with Asn. However, this
      mutant P450 2a-5 (F209N) and the corresponding mutant P450 2a-4 (L209N) exhibit
      different regiospecificites of androstenedione (AD) hydroxylase activity. While
      the former mutant catalyzes both AD 15 alpha- and 7 alpha-hydroxylase activities
      at similar rates, the latter mutant maintains the original high specificity of AD
      15 alpha-hydroxylase activity. The AD hydroxylase activities in chimeric enzymes
      of the mutants L209N and F209N show that the regiospecificites are determined by
      the carboxy-terminal halves of the P450 molecules. Mutations at each of the four
      different residues within the carboxy-terminal halves indicate that the
      differences in regiospecificity are determined by the Val/Ala mutation at
      position 481. As the size of the hydrophobic amino acid at position 481 becomes
      larger (Ala < Val < Ile), the regiospecificities toward the C15 position of the
      AD molecule are dramatically increased. The regiospecificity is also increased by
      placing positively-charged Arg at position 481, although the remaining 15 alpha
      hydroxylase activity in this mutant is considerably lower than the other P450s.
      The results indicate that the size of the residue at position 481 is a key factor
      in regulating the regiospecificity of AD hydroxylase activity in the P450s.
      Modeling AD in the substrate-heme pocket of bacterial P450 101A provided further
      support that residue 481 may reside near the steroid molecule so as to possibly
      affect the AD hydroxylase activity.

PMID- 7711026
TI  - Evidence for veratryl alcohol as a redox mediator in lignin peroxidase-catalyzed
      oxidation.
AB  - We have examined the hypothesis that veratryl alcohol (VA) may act as a redox
      mediator in lignin peroxidase (LiP)-catalyzed oxidations. The oxidation of
      chlorpromazine (CPZ) by this system was used to evaluate this hypothesis.
      Chlorpromazine can be oxidized by one electron to form a stable cation radical
      (CPZ.+). This cation radical can be oxidized by another electron to the sulfoxide
      (CPZSO). These oxidation steps are easily monitored, making CPZ a useful chemical
      to investigate redox mediation by VA. Lignin peroxidase oxidized CPZ to CPZ.+
      whether or not VA was present. The inclusion of VA, however, stimulated CPZ
      oxidation to CPZ.+ and subsequent oxidation of CPZ.+ to CPZSO. In the absence of
      VA, the initial rates of CPZ oxidation by LiP were CPZ concentration-dependent.
      However, when saturating concentrations of VA were added, the oxidation of CPZ
      and CPZ.+ became independent of CPZ concentration. When the oxidation of VA to
      veratryl aldehyde was examined, increasing concentrations of CPZ produced a lag
      in veratryl aldehyde appearance proportional to the concentration of CPZ.
      Conversely, increasing concentrations of VA never inhibited CPZ oxidation.
      Transient-state kinetic studies indicated that both VA and CPZ reduced the
      compound I and compound II forms of LiP. However, when saturating concentrations
      of VA were utilized, LiP turnover was independent of CPZ concentration. We
      suggest these data demonstrate that VA may act as a redox mediator for the
      indirect oxidation of compounds by LiP.

PMID- 7711027
TI  - Escherichia coli UMP-kinase, a member of the aspartokinase family, is a hexamer
      regulated by guanine nucleotides and UTP.
AB  - The pyrH gene, encoding UMP-kinase from Escherichia coli, was cloned using as a
      genetic probe the property of the carAB operon to be controlled for its
      expression by the concentration of cytoplasmic UTP. The open reading frame of the
      pyrH gene of 723 bp was found to be identical to that of the smbA gene [Yamanaka,
      K., et al. (1992) J. Bacteriol. 174, 7517-7526], previously described as being
      involved in chromosome partitioning in E. coli. The bacterial UMP-kinase did not
      display significant sequence similarity to known nucleoside monophosphate
      kinases. On the contrary, it exhibited similarity with three families of enzymes
      including aspartokinases, glutamate kinases, and Pseudomonas aeruginosa carbamate
      kinase. UMP-kinase overproduced in E. coli was purified to homogeneity and
      analyzed for its structural and catalytic properties. The protein consists of six
      identical subunits, each of 240 amino acid residues (the N-terminal methionine
      residue is missing in the expressed protein). Upon excitation at 295 nm, the
      bacterial enzyme exhibits a fluorescence emission spectrum with maximum at 332 nm
      which indicates that the single tryptophan residue of the protein (Trp119) is
      located in a hydrophobic environment. Like other enzymes involved in the de novo
      synthesis of pyrimidine nucleotides, UMP-kinase of E. coli is subject to
      regulation by nucleotides: GTP is an allosteric activator, whereas UTP serves as
      an allosteric inhibitor. UTP and UDP, but none of the other nucleotides tested
      such as GTP, ATP, and UMP, enhanced the fluorescence of the protein. The
      sigmoidal shape of the dose-response curve indicated cooperativity in binding of
      UTP and UDP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711028
TI  - Role of the C-terminal tail region in the self-assembly of lambda-repressor.
AB  - Acrylamide quenching of the tryptophan fluorescence of the lambda-repressor at
      different protein concentrations indicates that one of the three tryptophan
      residues, W129, W142, and W230, undergoes a change in environment upon self
      assembly, from dimer to associated species. Quenching data suggest that this
      tryptophan residue is inaccessible to low concentrations of acrylamide and is
      blue-shifted in the associated form. In the dimer, this tryptophan residue is
      highly accessible to acrylamide and is red-shifted. NBS oxidation, at protein
      concentrations which favor the associated form, showed that this tryptophan is
      also significantly protected from NBS oxidation. HPLC peptide mapping of NBS
      oxidized lambda-repressor, amino acid analysis, and sequencing indicate that the
      protected, blue-shifted tryptophan is tryptophan 230. A mutant repressor (F235C)
      was specifically labeled at Cys 235 with an environment-sensitive probe,
      acrylodan. The acrylodan fluorescence of the labeled F235C lambda-repressor
      undergoes a significant blue-shift, accompanied by fluorescence enhancement, upon
      protein association. Along with other genetic evidence, these results suggest
      involvement of the C-terminal tail region in the self-assembly of the lambda
      repressor.

PMID- 7711029
TI  - Identification and characterization of variants of tick anticoagulant peptide
      with increased inhibitory potency toward human factor Xa.
AB  - Tick anticoagulant peptide (TAP) is a specific and potent inhibitor of factor Xa
      (fXa), a central enzyme in the blood clotting cascade. As such, TAP is a
      potential antithrombotic agent. Site-directed mutagenesis studies were undertaken
      to determine the feasibility of increasing the inhibitory potency of TAP toward
      fXa. The amino acid substitutions Tyr-1 to Trp (Y1W) and Asp-10 to Arg (D10R)
      increased inhibitory potency toward human fXa by 2.5- and 4-fold, respectively.
      The increased inhibitory potency reflected a decrease in the rate constant for
      dissociation of the final fXa-TAP inhibitory complex. The double mutant,
      Y1W/D10R, exhibited an inhibition constant of 10 pM, a 37-fold enhancement of
      inhibitory potency toward human fXa. The improvement in inhibitory potency was
      less pronounced (12-fold) with dog fXa wherein Kis of 220 and 18 pM were observed
      for wild-type TAP and the double mutant, respectively. Mutation of Tyr-1 to Glu
      (Y1E) generated a weaker inhibitor (Ki = 2 nM) that bound human fXa more slowly.
      However, no change in inhibitory potency toward human fXa was observed when Tyr-1
      was replaced by Phe. Taken together, these observations are consistent with the
      view that a hydrophobic amino acid at the N-terminus of TAP may be a determinant
      of inhibitory potency. Decreases by 3-4 orders of magnitude in inhibitory potency
      were noted upon mutation of Asn-2 and Leu-4 of TAP, further implicating the N
      terminal domain as an important determinant of inhibitory potency.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7711030
TI  - Characterization of putative polyphosphoinositide binding motifs from
      phospholipase C beta 2.
AB  - Several phosphatidylinositol 4,5-bisphosphate (PtdInsP2)-regulated actin-binding
      proteins and most phosphoinositide-specific phospholipases C (PI-PLCs) comprise a
      basic amino acid motif (KxxxKxKK, where x denotes any amino acid), which was
      previously suggested to represent a PtdInsP2-binding site commonly present in
      these proteins. We have shown earlier that a peptide corresponding to amino acids
      448-464 of human PLC beta 2 (LPSPEDLRGKILIKNKK, peptide P1) markedly and
      specifically stimulated the activity of this enzyme [Simoes et al. (1993) FEBS
      Lett. 331, 248]. Here, we present a detailed analysis of the effects of various
      peptides related to peptide P1 aimed at understanding the mechanisms of peptide
      mediated PLC beta 2 stimulation. Peptide KILIKNKK (P2), which comprises only the
      basic amino acid consensus motif, also stimulated PLC beta 2, although higher
      concentrations were required to observe this stimulatory effect. The effects of
      P1 and P2 were not additive, indicating that the two peptides affect PLC beta 2
      activity via the same mechanism. Peptide LPSPEDLRG (P3), composed of the amino
      terminal half of P1, did not affect the activity of PLC beta 2. Peptide
      KILIKNKKQFSGPTSS (P4), which includes the nine amino acids flanking the carboxy
      terminus of the KILIKNKK motif within the sequence of PLC beta 2, stimulated the
      enzyme but was indistinguishable in potency from P2. Circular dichroism analysis
      revealed that peptide P1 changes its conformation in the presence of PtdInsP2 but
      not in the presence of other phospholipids including phosphatidylinositol 4
      phosphate. The results suggest that the basic amino acid sequence physically
      interacts with PtdInsP2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711031
TI  - Calmodulin binding sites of the skeletal, cardiac, and brain ryanodine receptor
      Ca2+ channels: modulation by the catalytic subunit of cAMP-dependent protein
      kinase?
AB  - In this study, we define calmodulin binding sites of skeletal, cardiac, and brain
      ryanodine receptor (RYR) Ca2+ channels. Cardiac and brain RYR peptides
      corresponding to the calmodulin binding sites present in the skeletal RYR
      [Menegazzi, P., et al. (1994) Biochemistry 33, 9078-9084] were synthesized, and
      their interaction with calmodulin was monitored by fluorescent techniques. The
      central portions of the skeletal, cardiac, and brain RYR protomers display one
      high (CaM1; Kd ranging between 2.7 and 10.2 nM) and one low affinity (CaM2; Kd
      ranging between 116 and 142 nM) calmodulin binding site. Depending on the RYR
      model having 4 or 12 transmembrane segments, a third calmodulin binding site
      (CaM3) was identified a few residues upstream from the putative transmembrane
      segment M1 or M5. Its affinity for calmodulin varied between the RYR isoforms:
      the cardiac RYR CaM3 displays a high affinity (9.09 +/- 1.0 nM, n = 5), while the
      skeletal and brain RYR CaM3 have low affinity, the lowest affinity being
      displayed by the brain isoform (234 +/- 39 nM, n = 3). The RYRs calmodulin
      binding site CaM1 encompasses the sequence Arg-His-Arg-Val(Ile)-Ser-Leu, which is
      phosphorylated in vitro by the catalytic subunit of the cAMP-dependent protein
      kinase. Phosphorylation of RYR PM1 peptides occurs on the Ser, corresponding to
      amino acid number 2919, 3020, and 3055 of the brain, cardiac, and skeletal RYR
      protomers, respectively. We found that phosphorylation of the RYR PM1 peptides
      was inhibited by calmodulin binding and that the formation of the PM1 peptide
      calmodulin complex was inhibited by peptide phosphorylation. These data indicate
      that the effect of calmodulin binding to RYR CaM1 may be regulated by the
      phosphorylation state of the Ser residue localized within the sequence Arg-His
      Arg-Val(Ile)-Ser-Leu.

PMID- 7711032
TI  - Iron binding, a new function for the reticulocyte endosome H(+)-ATPase.
AB  - The significance of the H(+)-ATPase in iron absorption by rabbit reticulocytes is
      explored using isolated endosomes, effects of inhibitors, and the purified proton
      pump. We have recently reported H(+)-ATPase-mediated iron transfer across a
      liposomal membrane (Li et al., 1994). In this report, the effect of H(+)-ATPase
      inhibitors on iron mobilization is investigated at pH 6.0 in the presence of 15
      microM FCCP in order to dissociate 59Fe(III) from transferrin and eliminate the
      kinetic effects of acidification by the ATPase. Iron transport by isolated
      endosomes is decreased 50% by the cation pore inhibitor dicyclohexylcarbodiimide
      (DCCD) for ascorbate-mediated iron mobilization and increased by 40-50% when NADH
      and ferrocyanide are used as electron donors. In contrast, the ATPase hydrolysis
      inhibitors N-methylmaleimide (NEM) and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole
      (NBD) increase iron mobilization when NADH and ferrocyanide are used as
      reductants but have negligible effects for ascorbate. The differential inhibition
      or enhancement by DCCD, NEM, and NBD with respect to the reductants used for
      mobilization indicates that the H(+)-ATPase may be involved in the multiple
      pathways or iron transport found in isolated rabbit reticulocyte endosomes.
      Effects of inhibitors of ATP hydrolysis suggest significant structural
      interactions between the proton pump and sites for iron binding and/or reduction.
      The isolated H(+)-ATPase binds iron as revealed by using nondenaturing
      electrophoretic and chromatographic methods. One class of iron binding sites is
      suggested to be the 17.5 kDa proton pore subunits of the H(+)-ATPase which also
      covalently react with DCCD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711033
TI  - DNA condensation by the rat spermatidal protein TP2 shows GC-rich sequence
      preference and is zinc dependent.
AB  - Transition protein-2 (TP2), isolated from rat testes, was recently shown to be a
      zinc metalloprotein. We have now carried out a detailed analysis of the DNA
      condensing properties of TP2 with various polynucleotides using circular
      dichroism spectroscopy. The condensation of the alternating copolymers by TP2
      (incubated with 10 microM ZnSO4), namely, poly(dG-dC).poly(dG-dC) and poly(dA
      dT).poly(dA-dT), was severalfold higher than condensation of either of the
      homoduplexes poly(dG).poly-(dC) and poly(dA).poly(dT) or rat oligonucleosomal
      DNA. Between the two alternating copolymers, poly(dG-dC).poly(dG-dC) was
      condensed 3.2-fold more effectively than poly(dA-dT).poly(dA-dT). Preincubation
      of TP2 with 5 mM EDTA significantly reduced its DNA-condensing property.
      Interestingly, condensation of the alternating copolymer poly(dI-dC).poly(dI-dC)
      by TP2 was much less as compared to that of poly(dG-dC).poly(dG-dC). The V8
      protease-derived N-terminal fragment (88 aa) condensed poly(dA-dT).poly(dA-dT) to
      a very small extent but did not have any effect on poly(dG-dC).poly-(dG-dC). The
      C-terminal fragment (28 aa) was able to condense poly(dA-dT).poly(dA-dT) more
      effectively than poly(dG-dC).poly(dG-dC). These results suggest that TP2 in its
      zinc-coordinated form condenses GC-rich polynucleotides much more effectively
      than other types of polynucleotides. Neither the N-terminal two-thirds of TP2
      which is the zinc-binding domain nor the C-terminal basic domain are as effective
      as intact TP2 in bringing about condensation of DNA.

PMID- 7711034
TI  - Antifibrinolytic effect of recombinant apolipoprotein(a) in vitro is primarily
      due to attenuation of tPA-mediated Glu-plasminogen activation.
AB  - The effect of a 17-kringle form of recombinant apo(a) [r-apo(a)] on in vitro
      fibrin clot lysis was studied. In these assays, fibrin clots were formed in the
      wells of microtiter plates, and lysis of the clots was monitored by measurement
      of the turbidity at 405 nm. The results indicate that r-apo(a) produces a dose
      dependent antifibrinolytic effect in clots formed using either purified
      components or barium-adsorbed plasma. This effect was found to be independent of
      clot structure, since lysis of clots formed using both high and low
      concentrations of thrombin was prolonged by r-apo(a) to the same extent. The two
      components of the antifibrinolytic effect of r-apo(a) were determined to be (i)
      attenuation of tPA-mediated plasminogen activation (the major component) and (ii)
      inhibition of plasmin degradation of fibrin, although r-apo(a) did not directly
      attenuate plasmin activity, as measured by S-2251 hydrolysis. r-Apo(a) interfered
      most substantially with tPA-mediated activation of Glu-plasminogen and less
      substantially with tPA-mediated Lys-plasminogen activation and urokinase-mediated
      activation of plasminogen. In summary, we have demonstrated that apo(a) is able
      to attenuate fibrin clot lysis in vitro, primarily as a consequence of the
      interference by apo(a) with tPA-mediated Glu-plasminogen activation. These
      studies illuminate possible mechanisms by which Lp(a) may contribute to the
      development of vascular disease in vivo.

PMID- 7711035
TI  - Relative conformational stabilities of single-chain pocket and groove-shaped
      antibody active sites including HCDR transplant intermediates.
AB  - Stability measurements of SCA 04-01/212 (anti-ssDNA) which possesses a groove
      shaped active site were performed by Gdn-HCl-induced unfolding, analyzed assuming
      a simple two-state equilibrium, and expressed as the free energy of unfolding,
      delta Gn-u. A delta Gn-u of 1.44 +/- 0.13 kcal/mol was determined experimentally
      for SCA 04-01/212. In addition, the conformational stabilities of HCDR
      transplants, hybrid antibody molecules resulting from the transplantation of
      HCDRs from SCA 4-4-20 (anti-fluorescein) into the corresponding regions of 04-01
      in all combinations, were determined using the identical protocol applied to SCA
      04-01. On the basis of the results of these stability experiments, the HCDR
      transplants were categorized into three groups, representing low, intermediate,
      and high stability. Data were discussed in terms of the relationships between
      structure-function and conformational stability pertaining to the groove-shaped
      antibody active site of SCA 04-01/212 and the pocket-shaped active site of SCA 4
      4-20/212.

PMID- 7711036
TI  - Inhibitory mechanism of serpins. Interaction of thrombin with antithrombin and
      protease nexin 1.
AB  - The mechanism for the inhibition of thrombin by the serpins antithrombin and
      protease nexin 1 has been investigated using several kinetic techniques at pH 7.9
      and 37 degrees C with an ionic strength of 0.3 M. Rapid kinetic studies
      demonstrated that a two-step mechanism for the formation of the stable thrombin
      serpin complex applied to both serpins. The inhibition constant for the initial
      thrombin-antithrombin complex was 265 microM, and the rate constant for the
      conversion of this complex to the final one was 3.9 s-1; the corresponding values
      for PN1 were 3.4 microM and 6.0 s-1. By using slow-binding kinetics, it was
      possible to obtain estimates of the second-order rate constants for the formation
      of the stable thrombin-serpin complexes (1.2 x 10(4) and 1.5 x 10(6) M-1 s-1 for
      antithrombin and protease nexin 1, respectively) and the dissociation constants
      for these complexes (< 1 nM for both serpins). The influence of viscosity on the
      reactions indicated that the rate of interaction of both serpins with thrombin
      was diffusion-controlled. Moreover, the results indicated that the initial
      complex reacted more rapidly to form the stable complex than it dissociated to
      free enzyme and inhibitor; i.e., the behavior of the serpins was analogous to
      that of "sticky" substrates. By using the results from slow-binding, viscosity,
      and rapid kinetic studies, it was possible to set values for all of the rate
      constants for the interactions of antithrombin and protease nexin 1 with
      thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711037
TI  - Autophosphorylation of smooth muscle myosin light chain kinase at its regulatory
      domain.
AB  - Autophosphorylation of smooth muscle myosin light chain kinase was initially
      reported by Foyt et al. [Foyt, H. L., & Means, A. R. (1985) J. Cyclic Nucleotide
      Protein Phosphorylation Res. 260, 8978-8983], however, the effects of
      autophosphorylation on the kinase activity as well as the location of the sites
      have not been elucidated. Here we demonstrate that MLCK is autophosphorylated at
      three sites, Thr 803, Ser 815, and Ser 823, and this phosphorylation alters MLCK
      activity. Two phosphorylation sites are located in the regulatory domain of the
      kinase, the threonine site toward the autoinhibitory region and the serine site
      (Ser 815) in close proximity to the calmodulin anchoring site. The
      autophosphorylation was significantly inhibited by the binding of calmodulin. The
      autophosphorylation at Thr 803 is an intramolecular process, and the alignment of
      the basic amino acid residues nearby Thr 803 was highly homologous to the
      phosphorylation site of myosin light chain, suggesting that the regulatory site
      is in close proximity to the catalytic site in the three-dimensional structure.
      The phosphorylation at the threonine site activated the calmodulin-independent
      activity while the phosphorylation at the serine site inhibited the calmodulin
      dependent activity due to a decrease in the affinity for calmodulin. This finding
      shows another example of the activation of calmodulin-dependent kinases by
      autophosphorylation at its autoinhibitory region and provides a new clue for
      understanding the calmodulin/MLCK signalling pathway.

PMID- 7711038
TI  - An L40C mutation converts the cysteine-sulfenic acid redox center in enterococcal
      NADH peroxidase to a disulfide.
AB  - Multiple sequence alignments including the enterococcal NADH peroxidase and NADH
      oxidase indicate that residues Ser38 and Cys42 align with the two cysteines of
      the redox-active disulfides found in glutathione reductase (GR), lipoamide
      dehydrogenase, mercuric reductase, and trypanothione reductase. In order to
      evaluate those structural determinants involved in the selection of the cysteine
      sulfenic acid (Cys-SOH) redox centers found in the two peroxide reductases and
      the redox-active disulfides present in the GR class of disulfide reductases, NADH
      peroxidase residues Ser38, Phe39, Leu40, and Ser41 have been individually
      replaced with Cys. Both the F39C and L40C mutant peroxidases yield active-site
      disulfides involving the new Cys and the native Cys42; formation of the Cys39
      Cys42 disulfide, however, precludes binding of the FAD coenzyme. In contrast, the
      L40C mutant contains tightly-bound FAD and has been analyzed by both kinetic and
      spectroscopic approaches. In addition, the L40C and S41C mutant structures have
      been determined at 2.1 and 2.0 A resolution, respectively, by X-ray
      crystallography. Formation of the Cys40-Cys42 disulfide bond requires a movement
      of Cys42-SG to a new position 5.9 A from the flavin-C(4a) position; this is
      consistent with the inability of the new disulfide to function as a redox center
      in concert with the flavin. Stereochemical constraints prohibit formation of the
      Cys41-Cys42 disulfide in the latter mutant.

PMID- 7711039
TI  - 1H NMR of A beta amyloid peptide congeners in water solution. Conformational
      changes correlate with plaque competence.
AB  - To begin to examine the structural basis for the deposition of soluble A beta
      amyloid peptide onto senile plaques in Alzheimer's disease, we have prepared A
      beta congeners and measured their activity in an in vitro plaque growth assay.
      The N-terminal fragment, A beta (1-28)-OH, was inactive at all pH values tested.
      While the central fragment, A beta (10-35)-NH2, and the full length peptide, A
      beta (1-40)-OH, were inactive below pH 4, both were active (plaque competent)
      between pH 5 and 9. The active and inactive fragments were studied by nuclear
      magnetic resonance spectroscopy in water at submillimolar concentrations at pH
      2.1 and 5.6. Changes in chemical shifts, coupling constants, and nuclear
      Overhauser enhancements indicate a pH dependent folding transition in A beta (10
      35)-NH2 as it becomes active. The conformation of the active fragment is not
      helical, and preliminary data indicate the presence of several turns and at least
      two short strands. In contrast, the inactive fragment A beta (1-28)-OH did not
      undergo a similar folding transition. Earlier nuclear magnetic resonance studies
      of amyloid peptides in fluorinated alcohols or detergent micelles at low pH
      described a helical conformation and proposed a helix to sheet transition in
      plaque formation; the present study demonstrates that no such conformations are
      present in water under conditions where the peptides can adhere to authentic
      amyloid plaques.

PMID- 7711040
TI  - Three-dimensional solution structure of Cucurbita maxima trypsin inhibitor-V
      determined by NMR spectroscopy.
AB  - The solution structure of Cucurbita maxima trypsin inhibitor-V (CMTI-V), which is
      also a specific inhibitor of the blood coagulation protein, factor XIIa, was
      determined by 1H NMR spectroscopy in combination with a distance-geometry and
      simulated annealing algorithm. Sequence-specific resonance assignments were made
      for all the main-chain and most of the side-chain hydrogens. Stereospecific
      assignments were also made for some of the beta-, gamma-, delta-, and epsilon
      hydrogens and valine methyl hydrogens. The ring conformations of all six prolines
      in the inhibitor were determined on the basis of 1H-1H vicinal coupling constant
      patterns; most of the proline ring hydrogens were stereospecifically assigned on
      the basis of vicinal coupling constant and intraresidue nuclear Overhauser effect
      (NOE) patterns. Distance constraints were determined on the basis of NOEs between
      pairs of hydrogens. Dihedral angle constraints were determined from estimates of
      scalar coupling constants and intraresidue NOEs. On the basis of 727 interproton
      distance and 111 torsion angle constraints, which included backbone phi angles
      and side-chain chi 1, chi 2, chi 3, and chi 4 angles, 22 structures were
      calculated by a distance geometry algorithm and refined by energy minimization
      and simulated annealing methods. Both main-chain and side-chain atoms are well
      defined, except for a loop region, two terminal residues, and some side-chain
      atoms located on the molecular surface. The average root mean squared deviation
      in the position for equivalent atoms between the 22 individual structures and the
      mean structure obtained by averaging their coordinates is 0.58 +/- 0.06 A for the
      main-chain atoms and 1.01 +/- 0.07 A for all the non-hydrogen atoms of residues 3
      40 and 49-67. These structures were compared to the X-ray crystallographic
      structure of another protein of the same inhibitor family-chymotrypsin inhibitor
      2 from barley seeds [CI-2; McPhalen, C. A., & James, M. N. G. (1987) Biochemistry
      26, 261-269]. The main-chain folding patterns are highly similar for the two
      proteins, which possess 62% sequence differences. However, major differences are
      noted in the N- and C-terminal segments, which may be due to the presence of a
      disulfide bridge in CMTI-V, but not in CI-2.

PMID- 7711041
TI  - Backbone dynamics of trp repressor studied by 15N NMR relaxation.
AB  - Backbone dynamics of trp repressor, a 25 kDa DNA binding protein, have been
      studied using 15N relaxation data measured by proton-detected two-dimensional 1H
      15N NMR spectroscopy. 15N spin-lattice relaxation time (T1), spin-spin relaxation
      time (T2), and heteronuclear NOEs were determined for all visible backbone amide
      15N nuclei. Monte Carlo simulations of the amplitudes of backbone motions led to
      the conclusion that a wobbling in a cone model with consideration of the
      anisotropic reorientation of the molecule was appropriate to describe the
      underlying motions, allowing us to derive the semiangle of the cone (alpha) and
      the effective correlation time for internal motions (tau e) for each N-H bond
      vector. The final optimized rotational diffusion coefficients parallel (D
      parallel) and perpendicular (D perpendicular) to the unique axis of the molecule
      were found to be 1.48 +/- 0.06 x 10(7) and 1.15 +/- 0.05 x 10(7) s-1,
      respectively. The average semiangle of the cone (alpha) describing the amplitude
      of NH vector motions on the picosecond time scale was found to be 20.9 +/- 5.7
      degrees. Large amplitude motions on the picosecond time scale are found at both
      the N and C termini but are restricted in both the hydrophobic core and DNA
      binding regions.

PMID- 7711042
TI  - A calorimetric study of the thermal stability of barstar and its interaction with
      barnase.
AB  - The temperature-induced unfolding of single, double, and triple mutants of
      barstar, the specific intracellular protein inhibitor of barnase from Bacillus
      amyloliquefaciens, has been studied by high-sensitivity differential scanning
      calorimetry. The thermal unfolding of barstar mutants, where at least one of the
      two cysteine residues in the molecule had been replaced by alanine, follows a two
      state mechanism at neutral and alkaline pH. The unfolding enthalpy and heat
      capacity changes are slightly lower than those accepted for highly compact,
      small, globular proteins. We have found that at pH 2.5, where barstar seems to be
      in a molten globule state, the protein has a heat capacity between that of the
      native and the unfolded states and shows some tendency for association. Scanning
      calorimetry experiments were also extended to the barstar--barnase complex in the
      neutral and alkaline pH range. The binding constants obtained from DSC studies
      are similar to those already obtained from other (kinetic) studies. The
      interaction of barstar and barnase was also investigated by isothermal
      calorimetry in various buffers within the pH range 6.0-10.0 and a temperature
      range of 15-35 degrees C. The favorable enthalpy contribution to the binding is
      about 4 times higher than the entropic one at 25 degrees C. The overall data
      analysis of the combined calorimetric results has led to the thermodynamic
      characterization of barstar unfolding and the interaction of barstar and barnase
      over a wide range of temperatures.

PMID- 7711043
TI  - Key disulfide bonds in an insect hormone binding protein: cDNA cloning of a
      juvenile hormone binding protein of Heliothis virescens and ligand binding by
      native and mutant forms.
AB  - The hemolymph juvenile hormone binding protein (JHBP) from the early fifth instar
      larvae of Heliothis virescens (Lepidoptera, Noctuidae) has been purified, and
      three cDNA clones for this protein have been isolated from a fat body cDNA
      library constructed in bacteriophage lambda ZAP XR. The deduced amino acid
      sequence of the full-length clone predicts a mature protein consisting of 224
      residues, a molecular mass of 24,976 Da, and a pI of 5.29. Comparison of the
      amino acid sequence to that of the previously described JHBP from Manduca sexta
      shows 51% overall identity with highly conserved N- and C-terminal regions. One
      of the three clones bound photoactivatable analogs of juvenile hormones with much
      lower affinity than the other two. This clone had Phe150 in place of the expected
      Cys150 conserved in other JHBP clones. The F150C mutant of this clone regained
      native binding affinity. For native Hvir-JHBP, the affinity for [3H]JH I was
      lower under reducing conditions (87 nM) relative to a 40 nM affinity under
      nonreducing conditions. The importance of pairs of Cys residues was addressed by
      preparing Cys to Ala mutants at each site. Expressed proteins were tested for
      binding affinity by photoaffinity labeling with tritium-labeled JH analogs and by
      binding assays using (10R,11S)-[3H]JH I. Curiously, the C150A mutant retained
      full activity, implying that the aberrant C150F was dysfunctional due to steric
      hindrance rather than to a missing disulfide linkage. Likewise, C29A and C194A
      had binding affinities unchanged from that of the full-length wild-type
      clone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711044
TI  - Characterization of a urea induced molten globule intermediate state of
      glutaminyl-tRNA synthetase from Escherichia coli.
AB  - The urea-induced unfolding of glutaminyl-tRNA synthetase, a multidomain protein,
      has been studied by equilibrium and kinetic methods, using chemical modification,
      fluorescence, and CD spectroscopy. The far-UV CD, fluorescence, and sulfhydryl
      reactivity clearly demonstrated the existence of a stable intermediate state at
      around 2 M urea. The intermediate showed higher binding of 1-anilino-8
      naphthalenesulfonic acid. Furthermore, near-UV CD study of the intermediate
      showed significantly disrupted tertiary structure with only a small change in the
      secondary structure, which is a characteristic of molten globule states. The
      activation energies (delta G++) calculated from unfolding kinetics monitored by
      CD and fluorescence suggest that the intermediate state may be separated from the
      native and the unfolded state by high activation energy barriers.

PMID- 7711045
TI  - Siroamide: a prosthetic group isolated from sulfite reductases in the genus
      Desulfovibrio.
AB  - While isolating siroheme from enzymes or whole cells of Desulfovibrio species, it
      was discovered that the main product after metal removal and esterification was
      not the octamethyl ester derivative of sirohydrochlorin, but a monoamide,
      heptamethyl ester derivative. The structure of this derivative was established by
      mass spectrometry and NMR. Nuclear Overhauser enhancement measurements in
      combination with chemical shift analogy arguments indicate that the 2(1)-acetate
      has been stereospecifically amidated. Other cellular sources of siroheme were
      investigated, but only the octamethyl ester derivative was found, with no traces
      of the amide derivative. The results suggest that, in Desulfovibrio, the
      physiologically active prosthetic group may be an amidated form of siroheme.

PMID- 7711046
TI  - Oxygen reaction and proton uptake in helix VIII mutants of cytochrome bo3.
AB  - The oxygen reaction of wild-type and helix VIII mutants of cytochrome bo3 from
      Escherichia coli, and the associated proton uptake during this reaction, has been
      studied using flash photolysis of the CO complex of the reduced protein after
      rapid mixing with oxygen. We have focused on mutations in the transmembrane helix
      VIII where protonatable residues have been exchanged, and mainly on the inactive
      mutants (i.e., T352A, T359A, and K362L, -M, and -Q). The kinetics for electron
      transfer during oxidation for the mutants are similar to the wild-type; two rate
      constants of 3.2 x 10(4) and 3.4 x 10(3) s-1 (at 1 mM oxygen) are detected.
      Proton uptake is observed for wild-type as well as for the mutant enzymes, but
      the mutations within helix VIII have affected the rate of proton uptake; it is
      significantly accelerated in the mutants. These results show that none of the
      protonatable residues in helix VIII are required in the reaction between the
      fully reduced cytochrome bo3 and oxygen. We have also studied electron
      redistribution after photolysis of CO from the mixed-valence compound; we found
      three kinetic components for wild-type and the mutants T352A and T359A, but for
      K362M only the first and third components are observed, with amplitudes that are
      lower than those for the corresponding components in the wild-type enzyme,
      suggesting that the characteristics of internal electron transfer in the K362M
      mutant are different from those of the wild-type enzyme.

PMID- 7711047
TI  - Structural and functional effects of multiple mutations at distal sites in
      cytochrome c.
AB  - Multiple mutations at distally located sites have been introduced into yeast iso
      1 cytochrome c to determine the contributions of three amino acids to the
      structural and functional properties of this protein. The mutant proteins, for
      which high-resolution structures were determined, included all possible
      combinations of the substitutions Arg38Ala, Asn52Ile, and Phe82Ser. Arg38, Asn52,
      and Phe82 are all conserved in the primary sequences of eukaryotic cytochromes c
      and have been shown to significantly affect several properties of these proteins
      including protein stability, heme reduction potential, and oxidation state
      dependent conformational changes. The present studies show that the structural
      consequences of each amino acid substitution in combinatorial mutant proteins
      were similar to those observed in the related single-mutant proteins, and
      therefore no synergistic effect between mutation sites was observed for this
      feature. With respect to protein stability, the effect of individual mutations
      can be understood from the structural changes observed for each. It is found that
      stability effects of the three mutation sites are independent and cumulative in
      multiple-mutant proteins. This reflects the independent nature of the structural
      changes induced at the three distally located mutation sites. In terms of heme
      reduction potential two effects are observed. For substitution of Phe82 by
      serine, the mechanism by which reduction potential is lowered is different from
      that occurring at either the Arg38 or the Asn52 site and is independent of
      residue replacements at these latter two positions. For Arg38 and Asn52,
      overlapping interactions lead to a higher reduction potential than expected from
      a strict additive effect of substitutions at these residues. This appears to
      arise from interaction of these two amino acids with a common heme element,
      namely, the heme propionate A group. The present results underscore the
      difficulty of predicting synergistic effects of multiple mutations within a
      protein.

PMID- 7711048
TI  - Structural and electronic factors in heterolytic cleavage: formation of the Co(I)
      intermediate in the corrinoid/iron-sulfur protein from Clostridium
      thermoaceticum.
AB  - We have completed the first direct structural characterization of an enzyme-bound
      four-coordinate Co(I) intermediate, in this case for the corrinoid/iron-sulfur
      protein (C/Fe-SP) from Clostridium thermoaceticum. Extended X-ray absorption fine
      structure and X-ray edge spectroscopy of the active Co(I) state of the C/Fe-SP
      indicates a four-coordinate (distorted) square-planar structure where the best
      fit gives average Co-N(equatorial) distances of 1.87 +/- 0.01 A, corresponding to
      4.2 +/- 0.3 ligands. The X-ray edge spectrum of Co(I) C/Fe-SP contains a moderate
      intensity 1s-4p + "shake-down" (SD) transition and no 1s-3d peak (where SD
      transitions are indicative of square-planar geometries). X-ray edge results for
      the methyl-Co(III) form, reported earlier [Wirt, M. D., Kumar, M., Ragsdale, S.
      W., & Chance, M. R. (1993) J. Am. Chem. Soc. 115, 2146-2150], are consistent with
      a base-off methylcobamide structure. The absence of a ligated 5
      methoxybenzimidazole base in the methyl-Co(III) state is important since the base
      off form is predicted to predispose the Co-C bond toward heterolytic cleavage to
      form the four-coordinate Co(I) species concurrent with methyl transfer.
      Additionally, we have examined first-derivative X-ray edge spectra of Co(I) C/Fe
      SP, relative to edge spectra of a cobalt foil, as an indicator of effective
      nuclear charge on cobalt. The Co(I) C/Fe-SP edge position at 7720.5 +/- 0.3 eV is
      less than, but very close to, the value seen for the corresponding free Co(I)
      cobalamin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711049
TI  - Structural consequences of ammonia binding to the manganese center of the
      photosynthetic oxygen-evolving complex: an X-ray absorption spectroscopy study of
      isotropic and oriented photosystem II particles.
AB  - The structure and orientation of the manganese complex in NH3-treated photosystem
      II (PS II) membrane particles of spinach are being studied by X-ray absorption
      spectroscopy. On the basis of earlier work by our group, a structure for the
      tetranuclear manganese complex of PS II, which consists of two di-mu-oxo-bridged
      binuclear Mn units linked by a mono-mu-oxo group, has been proposed [Yachandra,
      V. K., et al. (1993) Science 260, 675-679]. The extended X-ray absorption fine
      structure (EXAFS) of the complex modified by NH3 binding in the S2-state is
      suggestive of an increase in the Mn-Mn distance of one of these units from 2.72
      +/- 0.02 to 2.87 +/- 0.02 A, whereas the Mn-Mn distance of the second unit seems
      to be unaffected by NH3 treatment. The elongation of one binuclear center could
      result from the replacement of one bridging mu-oxo by an amido group. The
      lengthening of one Mn-Mn distance means that, by NH3 treatment, the distance
      degeneracy of the 2.7 A Mn-Mn EXAFS interaction is removed. Consequently, the
      orientation of individual binuclear units with respect to the membrane normal
      becomes resolvable by EXAFS spectroscopy of partially oriented PS II membrane
      particles. The angle between the normal of the PS II-containing membrane and the
      Mn-Mn vector is determined to be 67 degrees +/- 3 degrees for the 2.87 A distance
      and 55 degrees +/- 4 degrees for the 2.72 A distance. Only small effects on
      position, shape, and orientation dependence of Mn K-edge spectra result from NH3
      treatment, indicating that the Mn oxidation state, the symmetry of the Mn ligand
      environment, and the orientation of the complex remain essentially unaffected in
      the annealed NH3 S2-state. Therefore, it seems likely that the angles determined
      for the ammonia-modified manganese complex are similar to the respective angles
      of the untreated complex. The structure of the manganese complex and its
      orientation in the membrane are discussed.

PMID- 7711050
TI  - Near-infrared resonance Raman spectra of Chloroflexus aurantiacus photosynthetic
      reaction centers.
AB  - Resonance Raman spectra of the photosynthetic reaction center isolated from the
      green bacterium Chloroflexus aurantiacus have been obtained with excitation in
      the near-infrared absorption bands of the special pair (P) and the accessory
      bacteriochlorophyll (B) using shifted-excitation Raman difference spectroscopy
      (SERDS). These spectra are compared with the previously reported Raman spectra of
      P and B in reaction centers from the purple bacterium Rhodobacter sphaeroides.
      The spectra of P and B from the two species are nearly identical. Common and
      distinctive attributes of these spectra include enhanced low-frequency (30-200 cm
      1) modes in P and the absence of strong Raman activity in modes higher than 1200
      cm-1 in both P and B. Also, the absolute scattering cross sections with
      excitation in the P band are unusually weak in both reaction centers, indicating
      that their excited states are rapidly vibronically dephased. The striking
      similarities between the P and B spectra in reaction centers from two very
      different bacterial species suggest that the common nuclear and electronic
      dynamics identified here are characteristic of photosynthetic reaction centers.

PMID- 7711051
TI  - Characterization of bacterial reaction centers having mutations of aromatic
      residues in the binding site of the bacteriopheophytin intermediary electron
      carrier.
AB  - We report the initial characterization of a series of reaction centers (RCs) from
      the photosynthetic bacterium Rhodobacter capsulatus having single or double
      mutations of phenylalanines 97 and 121 on the L polypeptide. Substitution of
      these aromatic amino acids, which may interact with the photoactive
      bacteriopheophytin associated with the L polypeptide (BPhL), was carried out to
      examine their possible roles in electron transfer, charge stabilization, and/or
      BPhL binding. In some mutant RCs, the wild-type pigment content is obtained while
      in certain others a bacteriochlorophyll (BChL) replaces BPhL. The mutant RCs with
      wild-type pigment content are found to have overall photochemistry effectively
      identical to that of wild-type RCs. This indicates aromatic residues at L97 and
      L121 are not critical factors in the charge separation process, although an
      approximate 2-fold increase in the rate of electron transfer from BPhL- to QA is
      observed in two mutants where residue L121 is leucine. In two double mutants
      where L121 is histidine and L97 is either valine or cysteine, BPhL is replaced
      with a BChl (denoted beta). This pigment content is surprising since in the
      native RC structure amino acid L121 is not in optimum geometry for coordination
      to the Mg in the center of the pigment macrocycle. Charge separation takes place
      in the beta-containing mutants with an approximately 70% yield of P+QA- at 285 K
      compared to approximately 100% for wild-type. The photochemistry of these new
      beta-type RCs is very similar to that reported previously for the beta RC from
      Rhodobacter sphaeroides wherein the same pigment change was induced by a mutation
      in the M polypeptide.

PMID- 7711052
TI  - The effects of variable glycosylation on the functional activities of
      ribonuclease, plasminogen and tissue plasminogen activator.
AB  - The relatively large size and dynamics of oligosaccharides can result in
      substantial shielding of functionally important areas of proteins to which they
      are attached, modulate the interactions of glycoconjugates with other molecules
      and affect the rate of processes which involve conformational changes. This
      review focuses on the occupancy of N-linked glycosylation sites on three enzymes,
      ribonuclease, plasminogen and tissue plasminogen activator. Each of these
      proteins occurs naturally as two populations of molecules, distinguished from
      each other only by the presence or absence of an oligosaccharide at one
      glycosylation site. The presence of an oligomannose sugar on ribonuclease (at Asn
      34) alters its overall dynamics, increases its stability towards proteinases and
      decreases its functional activity towards double-stranded RNA. The N-linked sugar
      on plasminogen (at Asn-288) within kringle 3 reduces the rate of the beta- to
      alpha-conformational change, modulates the transport of plasminogen into the
      extravascular compartment, decreases plasminogen binding to U937 cells and
      downregulates the activation of plasminogen by both urokinase and tissue
      plasminogen activator. Additionally, in fibrinolysis, within a ternary complex of
      fibrin, plasminogen and tissue plasminogen activator, the N-linked sugar of
      plasminogen hinders the initial interaction with tissue plasminogen activator
      (i.e., it alters Km). The presence of an N-linked glycan (at Asn-184) in the
      kringle 2 domain of tissue plasminogen activator hinders the rearrangement of
      this ternary complex, decreasing the turnover rate (Kcat).

PMID- 7711053
TI  - A third type of nucleoside diphosphate kinase from spinach leaves: purification,
      characterization and amino-acid sequence.
AB  - A third type of nucleoside diphosphate kinase (NDP kinase III), distinct from the
      previously described NDP kinases I and II (Nomura et al. (1991) Biochim. Biophys.
      Acta 1077, 47-55), was purified from spinach leaves to electrophoretic
      homogeneity. NDP kinase III was judged by SDS-PAGE and by gel filtration to have
      molecular masses of 17 kDa and 102 kDa, respectively, suggesting that it is
      composed of six subunits similarly to the other spinach isoforms, NDP kinases I
      and II. Amino-acid sequence analysis revealed the primary structure of NDP kinase
      III to be comprised of 153 amino-acid residues, the sequence of which exhibited
      61% and 53% homology with those of NDP kinases I and II, respectively. In the
      reaction catalyzed by the three isoforms, the order of Km as phosphate acceptor
      was determined as GDP << ADP for NDP kinase III, different from those observed
      for NDP kinase I (ADP << GDP) and for NDP kinase II (GDP = ADP). These results
      suggest that the three isoforms may have distinct roles in regulating
      intracellular 5'-di- and 5'-triphosphonucleotide levels in spinach leaves.

PMID- 7711054
TI  - Identification of the active site histidine in Staphylococcus hyicus lipase using
      chemical modification and mass spectrometry.
AB  - Staphylococcus hyicus lipase is a serine hydrolase. In order to identify the
      active site histidine of S. hyicus lipase we have chemically modified S. hyicus
      lipase with 1-bromo-octan-2-one. The enzyme is rapidly inactivated by this
      inhibitor with a half-time of 578 s at pH 6.5 and 30 degrees C. Addition of the
      enzyme's cofactor calcium increases the inactivation rate approx. 2-fold. When n
      hexadecylphosphocholine, a non-hydrolysable substrate analogue, is added the
      inactivation rate decreases about 3-fold, suggesting that a residue in the active
      site of S. hyicus lipase is involved in the inactivation reaction. Inactivation
      of S. hyicus lipase with 14C-labelled 1-bromo-octan-2-one shows that 1.4 moles of
      inhibitor per mole of lipase are incorporated. The results of an electrospray
      mass spectrometric study of the inactivated enzyme are consistent with this
      finding. In order to identify the modified residue, both the inactivated and the
      unmodified lipase were digested with cyanogen bromide followed by trypsin. The
      resulting peptides were analysed using HPLC and fast atom bombardment mass
      spectrometry. The results allow the modified residue to be assigned to the
      peptide Gly597-Lys612. Collision induced dissociation mass spectrometry allowed
      the modified residue to be identified as His-600. From these results we conclude
      that this residue forms part of the catalytic triad of S. hyicus lipase.

PMID- 7711055
TI  - Role of disulfide linkages in structure and activity of proteinase inhibitor from
      horsegram (Dolichos biflorus).
AB  - Proteinase inhibitor isolated from horsegram (Dolichos biflorus or Macrotyloma
      uniflorum) inhibited specifically the enzymes trypsin and chymotrypsin. The
      inhibitor contained seven disulfide linkages and was free from thiol groups. The
      inhibitor is resistant to denaturation by urea, guanidine hydrochloride or sodium
      dodecyl sulfate. Reduction of the inhibitor with dithiothreitol abolished both
      trypsin and chymotrypsin inhibitory activities. The kinetic plots of the
      reduction as followed by activity and loss in structure as reflected in the 257
      nm CD band could be superposed; loss in the activity paralleled the loss in
      structure. The kinetics of the reduction process was complex; reduction of the
      inhibitor was slow and depended on the concentration of DTT. Reduction of the
      disulfide linkages with DTT affected the tertiary structure significantly and
      secondary structure was not affected considerably. Fluorescence quenching by
      acrylamide and potassium iodide suggested the unfolding of the molecule due to
      reduction. Thus, disulfide linkages play a predominant role in maintaining the
      three-dimensional structure of the inhibitor.

PMID- 7711056
TI  - Thermal denaturation of beta-lactoglobulin: effect of protein concentration at pH
      6.75 and 8.05.
AB  - Previous work on the thermal denaturation of beta-lactoglobulin at about neutral
      pH and concentrations generally above 50 mg/ml has shown that the temperature of
      the maximum in the thermogram increases only slightly with concentration.
      Likewise, there is little if any concentration dependence at acid pH over a wide
      concentration range. However, so far as we are aware, no work has been described
      on the thermal denaturation of beta-lactoglobulin in the physiological range of
      protein concentration and pH appropriate to milk. We report measurements at pH
      6.75 and 8.05 in the concentration range 2-120 mg/ml and show that below about 50
      mg/ml the position of the maximum becomes strongly dependent on concentration,
      passing through a minimum near 25 mg/ml and increasing towards the lowest
      concentrations where measurements were practicable. Moreover, the narrow, well
      defined and nearly symmetrical thermal transition observed at high protein
      concentrations contrasts with a broader and more asymmetric curve at lower
      concentrations. An explanation for the behaviour seen at the lower protein
      concentrations is suggested, based on the temperature- and concentration
      dependent dissociation of the beta-lactoglobulin dimer and an associated
      conformational transition. The position of the maximum in the thermogram has a
      marked dependence on the rate of heating down to the lowest rate investigated of
      10 degrees C per hour, showing the importance of slow kinetic effects in the
      denaturation of this protein.

PMID- 7711057
TI  - Purification, identification and subcellular distribution of three predominant
      protein-tyrosine phosphatase enzymes in skeletal muscle tissue.
AB  - Protein-tyrosine phosphatases (PTPases) play a key role in the regulation of
      insulin action. In order to identify PTPases in skeletal muscle, the major site
      of insulin-mediated glucose disposal in vivo, we purified PTPases from rat muscle
      tissue fractions by a series of column chromatographic techniques. PTPase
      activities were assayed by measuring the dephosphorylation of a rat insulin
      receptor kinase domain, derivatized lysozyme and p-nitrophenylphosphate, and the
      enzymes were further characterized by immunoblotting. Of the total PTPase
      activity in muscle homogenates, 51-64% was localized to the solubilized
      particulate fraction, with the specific PTPase activity 3.3-fold and 5.6-fold
      higher in the particulate fraction towards RCM-lysozyme or the insulin receptor,
      respectively. The major peak (> 75%) of PTPase activity in the particulate
      fraction was purified further to 700-fold; 75% of this activity passed through a
      Blue-3GA column and revealed immunoreactivity for both LAR and SH-PTP2. PTPase
      activity retained on the Blue-3GA column contained PTPase1B. The major peak (>
      70%) from muscle cytosol was further purified to 1500-fold. After the Blue-3GA
      step, immunoblotting revealed both SH-PTP2 and PTPase1B in the cytosol fraction,
      but LAR was absent from this fraction. LRP (RPTP-alpha) was not detected by
      blotting the PTPase activities from the purified particulate or cytosol
      fractions. Immunodepletion studies demonstrated that LAR, SH-PTP2 and PTPase1B
      were quantitatively major PTPase activities in the initial muscle homogenate,
      together accounting for over 70% of the total activity towards RCM-lysozyme.
      These studies provide insight into the relative abundance and subcellular
      distribution of specific PTPases in muscle tissue that are involved in the
      regulation of reversible tyrosine phosphorylation in this tissue.

PMID- 7711058
TI  - Mutations in putative glycosylation sites of rat 11 beta-hydroxysteroid
      dehydrogenase affect enzymatic activity.
AB  - 11 beta-hydroxysteroid dehydrogenase (11-HSD) catalyzes the interconversion of
      corticosterone and 11-dehydrocorticosterone in rats, or cortisol and cortisone in
      humans. The 'liver' or 'Type I' isozyme is a widely distributed glycoprotein that
      utilizes NADP+ as a co-factor. To study the role of glycosylation in maintaining
      enzymatic activity, we introduced mutations into the two potential N-linked
      glycosylation sites (asparagine-X-serine, residues 158-160 and 203-205) predicted
      from the rat cDNA sequence. Mutagenesis was performed by a PCR based technique,
      and wild-type (WT) and mutant cDNAs were expressed in Chinese hamster ovary cells
      after cloning into the pCMV4 vector. At each putative glycosylation site,
      asparagine (N) was changed to glutamine (Q) or aspartic acid (D), and serine (S)
      changed to alanine (A). All three modifications of the first site (N158Q, N158D,
      S160A) had minimal (75-100% of WT) effects on dehydrogenase activity and caused a
      mild (50-75% of WT) decrease in reductase activity. In contrast, mutations at the
      second site had marked effects, with N203Q and N203D completely abolishing both
      dehydrogenase and reductase activities and S205A decreasing both activities to
      about 20% of WT. The double mutation of S160A and S205A also abolished all
      activity, even though the enzyme carrying each mutation alone was, at least,
      partially active. The results suggest that N203 (which is highly but not
      completely conserved in short chain dehydrogenase enzymes) is essential for
      activity of 11-HSD. N-linked glycosylation may be necessary for full activity or
      stability of the enzyme.

PMID- 7711059
TI  - Affinity-purification and identification of GrpE homologues from mammalian
      mitochondria.
AB  - We used affinity chromatography on DnaK columns to identify a mitochondrial GrpE
      homologue from bovine, porcine and rat liver mitochondria. The 24 kDa GrpE
      homologue bound specifically to the DnaK column and was not eluted with 1 M KCl
      but readily with 5 mM ATP. Sequence analysis of the bovine homologue (85
      residues) revealed 42% positional identity to mitochondrial GrpEp from S.
      cerevisiae and about 30% identity to the bacterial counterparts. Thus, GrpE
      homologues from higher and lower eukaryotes are highly conserved.

PMID- 7711060
TI  - Phosphorylation of the C-terminal domain of RNA polymerase II.
AB  - The CTD has become a focal point in the analysis of RNAP II. The unusual
      properties of the CTD, including its unique structure and high level of
      phosphorylation, have stimulated interest in understanding the role this domain
      plays in the transcription of protein-coding genes. Research during the past ten
      years suggests that the CTD may function at multiple steps in the transcription
      cycle and that its involvement is promoter dependent. The general idea, for which
      there is now considerable support, is that the CTD mediates the interaction of
      RNAP II with the transcription apparatus and that these interactions are
      influenced by the phosphorylation that occurs throughout the CTD. The temporal
      relationship between phosphorylation of the CTD and the progression of RNAP II
      through the transcription cycle has been established in a general sense. However,
      it is not clear that the modifications that occur at a given time are causally
      related to the progression of RNAP II beyond that point in the transcription
      cycle. The idea that phosphorylation of the CTD mediates the release of RNAP II
      from the preinitiation complex is an attractive one and consistent with a number
      of experimental results. However, an increasing number of observations suggest
      that CTD phosphorylation and promoter clearance may not be causally related. One
      possibility is that even though phosphorylation occurs concomitant with
      transcript initiation it plays no real role in the initiation process and is
      necessary only to establish an elongation competent form of the enzyme.
      Alternatively, CTD phosphorylation may play an essential role in the release of
      RNAP II from preinitiation complexes in vivo but may be dispensable in defined in
      vitro transcription systems. Finally it may be important to distinguish between
      promoter clearance as defined by RNAP moving off the transcriptional start site
      and the complete disruption of interactions between RNAP II and the preinitiation
      complex. Because of the extended nature of the CTD, RNAP II may remain tethered
      to factors assembled on the promoter even though a short transcript has been
      synthesized. Clearly additional research is necessary to (a) define the contacts
      made by the CTD in preinitiation complexes, (b) understand the relationship
      between the disruption of these contacts and CTD phosphorylation and (c)
      understand biochemically what is required to generate an elongation competent
      form of RNAP II. The possibility that the CTD plays a role in transcript
      elongation has been proposed since the discovery of the CTD [15].(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7711061
TI  - 3'-end cleavage and polyadenylation of mRNA precursors.

PMID- 7711062
TI  - The interaction of hedamycin and DC92-B in a sequence selective manner with DNA
      in intact human cells.
AB  - The sequence specificity of the pluramycin antibiotics hedamycin and DC92-B, was
      established in intact human cells using a linear amplification system. In this
      system an oligonucleotide primer is extended by Taq DNA polymerase up to a damage
      site. The products are run on a DNA sequencing gel and the damage can be
      determined to the exact base pair. The human repetitive alpha RI DNA was used as
      the target DNA sequence for these experiments. It was found that G residues were
      the main site of adduct formation, for both hedamycin and DC92-B. The sequences
      5'-TGT and 5'-CGT were the most intense sites of DNA damage. A comparison of the
      DNA damage intensity in intact cells and purified DNA revealed that the sequence
      position of adduct formation was very similar in the two environments. However, a
      densitometric comparison of the damage intensity in the two environments revealed
      significant differences. Two regions were found (120 and 130 bp in length) where
      the damage intensity was relatively lower in intact cells compared to purified
      DNA. But at the boundaries of these sequences, there were regions (approx. 50-60
      bp long) that were relatively more damaged in intact cells compared to purified
      DNA. One explanation of this phenomenon is the presence of a protecting
      nucleosome core on each of the 120/130 bp regions and flanking nucleosome linker
      regions of 50-60 bp. This postulated sequence phasing of the nucleosomes
      corresponds almost exactly with the major nucleosome phasing found in African
      green monkey cells. Also the centromere protein B binding site is found in the
      border region between the nucleosome core and linker DNA regions. Hedamycin and
      DC92-B produced nearly identical results in this human cell system.

PMID- 7711063
TI  - Cloning, sequencing and expression of two isoforms of the murine oct-1
      transcription factor.
AB  - Oct-1 is a ubiquitously expressed regulatory gene of the POU domain family. The
      Oct-1 protein binds to the octamer motif present in the control regions of a
      variety of genes such as the immunoglobulins, histone H2B and snRNAs. To learn
      about Oct-1 and its possible role in B-cell maturation, we have used oct-2 cDNA
      to screen a murine pre-B cell, cDNA library. Two cDNA clones were identical in
      their POU-homeo box DNA binding domain, but differed in their 3'-region. Whereas
      one clone (oct-1a) was very similar to its human oct-1 homologue, the other (oct
      1b), contained an additional 72 bp sequence (designated E1) at the serine
      threonine rich coding region (position 1485 of the human oct-1), and a deletion
      of another 72 bp sequence (designated E2) downstream (position 1920). These
      changes preserve the protein reading frame. DNA blot analysis indicates that
      murine oct-1 is a single copy gene and that the two oct-1 isoforms oct-1 is
      expressed as a large approximately 10 kb transcript in all the cell are generated
      by alternative RNA splicing. RNA blots showed that oct-1 is expressed as a large
      approximately 10 kb transcript in all the cell lines tested. PCR analysis of the
      E1 and E2 72 bp regions, indicated the presence of a third isoform containing
      both E1 and E2 (Oct-1c). Oct-1a and Oct-1b were present in all cell types
      examined, but the level of expression was lower in liver and spleen as compared
      to testis, thymus and kidney. The ratio of Oct-1b to Oct-1a ranged between 0.2 to
      0.5, for all tissues examined except for testis which expressed higher amounts of
      oct-1b and/or oct-1c. Our findings thus show that the pattern of expression of
      the oct-1 gene is more complex than hitherto thought.

PMID- 7711064
TI  - Expression of basic fibroblast growth factor and fibroblast growth factor
      receptor genes in cultured rat aortic smooth muscle cells.
AB  - Basic fibroblast growth factor (bFGF) exerts a differential effect on DNA
      synthesis, bFGF mRNA synthesis, and expression of FGF-receptor genes by cultured
      smooth muscle cells from aortae of newborn and adult rats (used as a model in
      atherosclerosis research). Cells from adult animals, are more sensitive to bFGF,
      and bFGF triggers its own mRNA synthesis. Moreover, the level of the transcript
      of the FGFR-1 gene (coding for the most abundant FGF-receptor in smooth muscle
      cells) is higher in smooth muscle cells from adult rats. In contrast, the FGFR-3
      gene only is expressed in smooth muscle cells from newborn rats. Crosslinking of
      [125I]bFGF to its receptor showed 130 kDa and 160 kDa complexes both in newborn
      and adult smooth muscle cells.

PMID- 7711065
TI  - Characterization of the polyubiquitin gene in the marine red alga Gracilaria
      verrucosa.
AB  - We have cloned a nuclear gene (UBI6R) and corresponding cDNAs that encode
      polyubiquitin in the florideophycidean red alga Gracilaria verrucosa. The gene
      encodes a polyubiquitin composed of six tandem ubiquitin units, followed by a
      single glutamine residue. The deduced amino acid sequences are identical among
      all six units, and identical to the ubiquitin of the florideophyte Aglaothamnion
      neglectum. There is high sequence similarity among the red algal ubiquitins and
      those of animals, green plants, fungi and several protists. Only one
      polyubiquitin gene was found by Southern hybridization analysis of G. verrucosa
      nuclear DNA. The upstream region of the gene is rich in putative cis-acting
      transcription-regulatory elements, including a putative heat-responsive element.
      Poly(A) addition to UBI6R mRNA was observed in cDNAs at four different sites,
      implicating the sequences AATAAA and (or) AGTAAA as poly(A) addition signals. The
      polyubiquitin genes of red algae show features of concerted evolution, but appear
      to be subject to less sequence homogenization than those of animals.

PMID- 7711066
TI  - dlk, pG2 and Pref-1 mRNAs encode similar proteins belonging to the EGF-like
      superfamily. Identification of polymorphic variants of this RNA.
AB  - dlk encodes a transmembrane protein member of the EGF-like family of homeotic
      proteins. dlk is expressed in the same type of neuroendocrine tissues and tumors
      as pG2, a gene cloned because of its differential expression in human
      pheochromocytomas versus neuroblastomas. Human dlk and pG2 cDNAs are around 98%
      similar in sequence, but the predicted proteins encoded by those genes are
      apparently unrelated. This fact suggested the existence of polymorphic variants
      of the same gene. We have sequenced again several pG2 and dlk clones in parallel.
      We identified a pG2 cDNA species corresponding to an alternatively spliced dlk
      mRNA, as well as several other variant forms of dlk mRNA. One of the pG2 clones
      resulted to be identical to human dlk and encode the same EGF-like protein. Pref
      1, a cDNA isolated from 3T3-L1 fibroblasts, encodes a putative protein possessing
      an extracellular EGF-like domain similar to dlk, but a different intracellular
      region. Analysis of sequence data from different clones obtained in our
      laboratory confirmed some of the differences between dlk and Pref-1. However, the
      putative difference in the intracellular regions of dlk and Pref-1 was due to
      sequence artifacts. These data suggest that dlk, pG2 and Pref-1 are variant
      products of the same gene.

PMID- 7711067
TI  - Isolation and expression of rat thymidylate synthase cDNA: phylogenetic
      comparison with human and mouse thymidylate synthases.
AB  - Two cDNA clones representing rat hepatoma thymidylate synthase (rTS) were
      isolated from a lambda ZAP II cDNA library using as a probe a fragment of the
      human TS cDNA. The two were identical except that one was missing 50 bp and the
      other 23 bp corresponding to the 5' coding region of the protein. The missing
      region was obtained by screening a rat genomic library. The open reading frame of
      rTS cDNA encoded 921 bp encompassing a protein of 307 amino acids with a
      calculated molecular mass of 35,015 Da. Rat hepatoma TS appears identical to
      normal rat thymus TS and the two sequences differ from mouse TS in the same eight
      amino acid residues. Six of these differences are in the first 21 amino acids
      from the amino-end. The human enzyme differed from rat and mouse TS at 17
      residues where the latter two were identical, with most changes being
      conservative in nature. The three species differed completely at only four sites.
      Because the mouse TS shares four amino acids with human TS at sites which differ
      from rTS and a comparable situation does not exist between rTS and human TS, it
      is suggested that mouse TS is closer to human TS phylogenetically than rTS. The
      polymerase chain reaction was used to subclone the protein coding region of rTS
      into a high expression vector, which expressed rTS in Escherichia coli to the
      extent of 10 to 20% of its cellular protein. Although the amino-end of the
      amplified TS was unblocked, that isolated from a FUdR-resistant rat hepatoma cell
      line contained mostly N-acetylmethionine on its N-terminal end, a finding that
      may have significant regulatory consequences, which are discussed. The TS level
      in the resistant cell line was 60 to 70-fold higher than normal which was found
      to be associated with both multiple gene copies and an expanded TS mRNA pool.

PMID- 7711068
TI  - The CRE consensus sequence in the synapsin I gene promoter region confers
      constitutive activation but no regulation by cAMP in neuroblastoma cells.
AB  - Synapsin I is implicated in the modulation of neurotransmitter release and in
      synaptogenesis and is regulated by phosphorylation. The rat and human synapsin I
      genes both carry CRE and TRE consensus sequences in their promoter regions. This
      suggested that protein kinase-mediated signal pathways might also regulate
      synapsin I activity at the level of gene expression and thus contribute, on a
      slower time scale, to synaptic plasticity. We have therefore investigated, in
      neuroblastoma cell lines, the effects of agents that activate protein kinases on
      synapsin I gene expression. Unexpectedly, treatment with forskolin/IBMX was not
      found to enhance synapsin I mRNA levels. Rather, it causes a decrease to
      approximately 50% within 1 day although several CRE-dependent control genes are
      strongly induced. The calcium ionophore, A23187, lowers synapsin I mRNA to
      approximately 75%, and the phorbol ester, TPA, is without effect. Transient
      expression of a CAT fusion gene under the control of the synapsin I promoter
      region is also inhibited by forskolin/IBMX, as well as by protein kinase A (PKA)
      overexpression, suggesting that the decrease of synapsin I mRNA in response to
      forskolin/IBMX is due to the inhibition of transcription. Mutation of the CRE
      consensus does not affect the response to PKA, but it reduces the constitutive
      activity of synapsin I promoter constructs down to 30-50%. Nuclease footprinting
      experiments demonstrate sequence-specific binding proteins from brain, liver and
      NS20Y cell nuclear extracts to the CRE consensus sequence of the rat synapsin I
      promoter.

PMID- 7711069
TI  - Analysis of the primary structure of the chloroplast isozyme of triosephosphate
      isomerase from rye leaves by protein and cDNA sequencing indicates a eukaryotic
      origin of its gene.
AB  - The primary structure of the chloroplast isozyme of triosephosphate isomerase
      from rye leaves was identified by protein and cDNA sequencing and compared to the
      deduced amino acid sequence of a cDNA for the cytosolic isozyme. The mature
      cytosolic and chloroplast isozyme proteins share 64% amino acid sequence
      identity. The cDNA for the chloroplast isozyme codes for a precursor protein
      consisting of an N-terminal transit peptide of Mr 4351 and a mature subunit of Mr
      27,282. Southern blot analysis indicates that the two rye isozymes are encoded by
      two independent single genes. Amino acid residues or sequence regions of basic
      functional relevance in known triosephosphate isomerases are strictly conserved
      in the chloroplast isozyme. The chloroplast isozyme contains 6 cysteine residues,
      instead of 4 in the cytosolic isozyme. A cysteine at position 143 of the
      chloroplast isozyme appears to be modified. Phylogenetic trees constructed on the
      basis of sequence comparisons for triosephosphate isomerases from different
      species of all major taxonomic groups indicate that the chloroplast isozyme is
      much more closely related to eukaryotic cytosolic enzymes than to eubacterial
      enzymes. The results indicate that the nuclear gene for the chloroplast isozyme
      originated with that for the cytosolic isozyme through duplication of an
      ancestral eukaryotic gene, rather than through gene transfer from a prokaryotic
      endosymbiont.

PMID- 7711070
TI  - Decay of globin mRNA during megakaryocytic differentiation of erythroleukemic
      cell line is accomplished through shortening of the poly(A) tail and degradation
      from the 3' end of the transcript.
AB  - Human erythroleukemic cell line K562 normally co-expresses erythroid and
      megakaryocytic genes, but treatment with an activator of the protein kinase C
      (PKC), tumor-promoting phorbol ester 12-myristate 13-acetate (PMA) shifts these
      cells toward megakaryocytic pathway of differentiation. This shift results in
      silencing of erythroid genes and in additional activation of megakaryocytic
      genes. It was shown that destabilization of the most abundant erythroid mRNA of
      K562 cells coding for fetal globin (gamma-globin,) is partially responsible for
      its silencing in phorbol ester-induced K562 cells. In this work the mechanism of
      the gamma-globin mRNA destabilization is further investigated. The results show
      that this process is accompanied by the progressive shortening of the gamma
      globin mRNA poly(A) tail. Also, degradation intermediates of gamma-globin mRNA
      observed during the course of PMA treatment are shown to contain an intact 5'
      end, but lack the sequences at the 3' end. Based on these findings, a model for
      the selective destabilization of the erythroid mRNAs during the course of
      megakaryocytic differentiation of K562 cells is proposed.

PMID- 7711071
TI  - Two transcripts are generated from the pancreatitis associated protein II gene by
      alternative splicing in the 5' untranslated region.
AB  - We have previously reported the coding sequence of the rat PAP II mRNA. We show
      in this paper the existence in rat pancreas of two forms of PAP II mRNA with
      identical coding sequence but a different 5'-untranslated region. We demonstrate
      that this is the result of a differential splicing.

PMID- 7711072
TI  - Sequence and putative secondary structure of group I introns in the nuclear
      encoded ribosomal RNA genes of the fungus Hymenoscyphus ericae.
AB  - Two putative group I introns in the nuclear ribosomal RNA genes of Hymenoscyphus
      ericae are described. One is in the small subunit gene about 30 nucleotides
      upstream of the 3' end of the gene at a site common to several other group I
      introns. The other is in the large subunit gene approx. 930 bp downstream of the
      5' end of the gene. This is the only report of an intron at this location.

PMID- 7711073
TI  - The structural genes for nitric oxide reductase from Pseudomonas aeruginosa.
AB  - The genes for nitric oxide reductase (norCB) from Pseudomonas aeruginosa were
      identified and sequenced. They are located about 2 kb upstream of nirS, the
      structural gene for nitrite reductase. norC and norB encode cytochrome c (16 kDa)
      and cytochrome b (52 kDa) subunits of the enzyme, respectively. norCB is
      immediately followed by an open reading frame encoding a protein of 612 residues.

PMID- 7711074
TI  - cDNA structure of rabbit C4b-binding protein alpha-chain. Preserved sequence
      motive in complement regulatory protein modules which bind C4b.
AB  - A full length cDNA clone for the alpha-chain of the rabbit complement regulatory
      protein C4b-binding protein (C4BP) was isolated from a liver cDNA library. The
      clone encoded an open reading frame of 597 amino acids, which included a signal
      peptide, eight short consensus repeats (SCR) and a carboxy terminal non-repeat
      region. Gel filtration of rabbit plasma and testing of fractions for factor I
      cofactor activity (C4BP-like) revealed two peaks of activity, the one with
      highest molecular weight corresponding in size to that of human C4b-binding
      protein. Comparison of the rabbit C4BP alpha-chain sequence with other SCR
      containing C3b/C4b binding proteins revealed highest sequence similarities
      between the second SCRs in C4BP from rabbit, human and murine species and SCRs at
      corresponding position in complement receptor 1 (CR1) whereas in decay
      accelerating factor (DAF), the third SCR was most similar. A conserved sequence
      motive was identified in these C4b-binding SCRs.

PMID- 7711075
TI  - cDNA encoding a chicken protein (CRP1) with homology to hnRNP type A/B.
AB  - The sequence of a cDNA encoding a putative chicken RNA-binding protein is
      reported. The C-terminal portion of the predicted protein is similar to a family
      of nucleic acid binding proteins that includes murine CArG box-binding factor CBF
      A, human hnRNP A/B, hepatitis B enhancer-binding protein E2BP, and AU-rich RNA
      binding protein AUF1. These proteins all have two consecutive RNA recognition
      motifs. However, the N-terminal 72 amino acids of this deduced chicken protein
      show no relation to the N-terminal sequences of the other proteins. We call this
      protein chicken ribonucleoprotein, CRP1.

PMID- 7711076
TI  - A homologue of the human MSS1 gene, a positive modulator of HIV-1 gene
      expression, is massively expressed in Xenopus oocytes.
AB  - Here the nucleotide sequence of a Xenopus homologue of the human MSS1 gene, a
      positive modulator of the HIV-1 Tat mediated transactivation in mammalian cells,
      is presented. This gene is highly conserved and almost exclusively expressed in
      Xenopus oocytes. We speculate about a possible role of this gene in the HIV-1
      Tat/TAR mediated transactivation in Xenopus oocytes.

PMID- 7711077
TI  - Xenopus PKN: cloning and sequencing of the cDNA and identification of conserved
      domains.
AB  - cDNA clone encoding Xenopus laevis PKN has been isolated from Xenopus kidney
      library. Sequencing of this clone has revealed a single open reading frame
      encoding a protein of 901 amino acids. Immunoprecipitate from cytoplasmic
      fraction of COS7 cells transfected with this cDNA construct using antiserum
      against bacterially expressed Xenopus PKN revealed arachidonic acid-dependent
      autophosphorylation activity. Comparison of the closely related sequences of
      human and rat PKN with a protein from evolutionarily distant Xenopus, revealed
      several highly invariant domains in the NH2-terminal regulatory regions,
      suggesting that they participate in binding interaction with arachidonic acid.

PMID- 7711078
TI  - The putative Drosophila NMDARA1 gene is located on the second chromosome and is
      ubiquitously expressed in embryogenesis.
AB  - We describe the cDNA sequence of a Drosophila gene located at 49D on the second
      chromosome. The predicted protein sequence has extensive homology (46% identity,
      76% similarity) along its entire length to the central portion of the mammalian
      brain-specific NMDARA1 glutamate binding protein. While RNA expression studies of
      the Drosophila protein shown that it is ubiquitously expressed throughout
      embryogenesis, there appears to be a selective accumulation of transcript in the
      precursor for the larval brain. The similarity in both expression and sequence
      suggests that the two proteins may share a conserved function.

PMID- 7711079
TI  - The complete nucleotide sequence of the mouse thyroid-specific enhancer-binding
      protein (T/EBP) gene: extensive identity of the deduced amino acid sequence with
      the human protein.
AB  - A mouse thyroid-specific enhancer-binding protein (T/EBP) gene and its flanking
      regions have been cloned and completely sequenced. The gene consists of 2 exons
      and exhibits high similarity (83-97%) to the rat sequence throughout the coding
      region and including an intron and up to 1.3 kbp upstream to the ATG initiation
      codon. A cDNA clone encoding human T/EBP has been also isolated and sequenced.
      Comparison of the deduced amino acid sequence of T/EBP revealed an extensive
      identity of 98% between mouse and the human protein.

PMID- 7711080
TI  - Cloning and sequence analysis of human thyroid transcription factor 1.
AB  - The thyroid transcription factor 1 (TTF-1) is a homeodomain-containing
      transcription factor that activates the transcriptional activity of thyroid
      specific gene promoters by binding to them. Hence, TTF-1 is crucial in the
      maintenance of the thyroid differentiation phenotype. The authors isolated and
      analysed the human TTF-1 gene, which shows a striking homology with the rat TTF-1
      gene.

PMID- 7711081
TI  - Sequence of the cDNA for the heart/muscle isoform of mouse cytochrome c oxidase
      subunit VIII.
AB  - We have isolated and sequenced cDNAs for the heart/muscle (H) isoform of mouse
      cytochrome c oxidase subunit VIII (COX VIII-H). The deduced protein sequence
      enables us to compare the heart/muscle COX VIII isoforms from several species and
      to determine that the most highly conserved region of this subunit is the C
      terminal domain.

PMID- 7711082
TI  - Nucleotide sequence of a gene cluster encoding ribosomal proteins in the
      thermoacidophilic crenarchaeon Sulfolobus acidocaldarius.
AB  - A 1.6 kb genomic DNA fragment derived from the extremely thermoacidophilic
      archaeon Sulfolobus acidocaldarius (DSM 639) comprises four open reading frames.
      The sequence contains three genes encoding crenarchaeal ribosomal proteins with
      apparent molecular masses of 6.3 kDa, 15.2 kDa and 9.9 kDa, which all represent
      strongly basic properties. These were identified by sequence comparison as RL46,
      RL31 and RL33. One open reading frame encodes a new polypeptide (22.1 kDa, pI =
      7.3) with no homology to known proteins. The latter is transcribed as a common
      mRNA with RL46 and RL31. This gene cluster immediately precedes another cluster
      including genes encoding the putative SRP receptor alpha subunit as well as the
      putative secEp.

PMID- 7711083
TI  - Nucleotide sequence of a Aspergillus parasiticus gene strongly repressed by
      thiamine.
AB  - A cDNA clone demonstrating a high degree of homology to the thiamine repressed
      nmt1 gene of Schizosaccharomyces pombe was isolated from the aflatoxigenic
      fungus, Aspergillus parasiticus. The deduced polypeptide of a cDNA clone from A.
      parasiticus had an amino acid sequence identity of 60% with that of the nmt1 gene
      of S. pombe. Transcription of the nmt1 gene homolog in the fungus was strongly
      inhibited by concentrations of thiamine of 2.0 microM or higher.

PMID- 7711084
TI  - Cloning and sequence analysis of the cDNA for bovine mitochondrial translational
      initiation factor 2.
AB  - The complete sequence of the cDNA encoding bovine mitochondrial translational
      initiation factor 2 (IF-2mt) has been obtained by library screening followed by
      3'-RACE PCR. The open reading frame for bovine IF-2mt encodes a protein of 727
      amino acids. The sequence of bovine IF-2mt exhibits 85% identity to human IF-2mt,
      but only 38% identity to yeast IF-2mt and 39% identity to Escherichia coli IF-2
      alpha.

PMID- 7711085
TI  - Maternal health in the age of AIDS: implications for health services in
      developing countries.
AB  - In developing countries, the HIV/AIDS epidemic will have a major impact on all
      phases of women's reproductive lives, and will alter many standard approaches to
      the management of MCH (maternal and child health) services related to fertility
      regulation, pregnancy, delivery and the postpartum period. AIDS-related increased
      caseloads, occupational risk to health workers and reduced resources will further
      compromise MCH services. MCH programme managers and service providers need to
      better understand the nature of both technical and service-related issues
      intersecting both the MCH and AIDS fields to mitigate this impact.

PMID- 7711086
TI  - Destinations unknown: the gender construction and changing nature of the sexual
      expressions of Thai youth.
AB  - This paper discusses qualitative findings from a study of the sexual awareness,
      lifestyles and related health service needs of young, single factory workers in
      Thailand. The context of this study is Thailand's growing industrialization, the
      deepening intensity of the threats to sexual health (especially regarding
      HIV/AIDS transmission) and the vulnerability of young migrant women. Findings
      from 18 focus group discussions held with groups of young (15-24) male and female
      factory workers are outlined with principal reference to the gender construction
      of sexuality. Key themes explored include attitudes towards courtship, marriage,
      sexual feelings and arousal, expressions of involvement in pre-marital sexual
      activities and the consequences of such activity. In conclusion there is some
      discussion of the implication for young women's sexual health, of the interplay
      of a measure of pre-marital intercourse and the continuing emotional barriers to
      effective use of contraception.

PMID- 7711087
TI  - Sexual behaviour of gay and bisexual men in eight European countries.
AB  - To compare the sexual behaviour and HIV risk reduction strategies of gay and
      bisexual men in Europe, a survey, disseminated via the gay press and gay
      associations, was conducted amongst gay and bisexual men in Austria, Switzerland,
      Germany, Denmark, France, Great Britain, Italy and the Netherlands during the
      autumn and winter of 1991. By end March of 1992, 12,347 completed questionnaires
      had been obtained. A preliminary analysis shows striking similarities in patterns
      of sexual behaviour of gay men in the 8 European countries but indicates that
      strategies of risk management concerning HIV and AIDS vary widely. While the
      majority of gay men have multiple partners, and intercourse is more common with
      stable partners than with causal partners. The proportion of men who, during the
      past 12 months, engaged in unprotected anal intercourse with a partner with
      different or unknown HIV-status ranged from 1/3 in East Germany to 1/6 in UK.
      However, reported incidence over the past 12 months of STDs, other than HIV
      infection, was similar in all countries (2%-3%). The reported HIV antibody
      prevalence varied from less than 7% in East Germany, Italy and the United Kingdom
      to 15% in Denmark and 17% in France. HIV risk reduction strategies appear to be
      most common in those countries where the gay community had been included in
      targeted prevention campaigns during the early phase of the AIDS epidemic.
      Considering the high proportion of gay men engaging in high risk activities it is
      imperative that prevention efforts are sustained and improved.

PMID- 7711088
TI  - Approaching the HIV epidemic: the community's response.
AB  - The HIV epidemic comes to people's attention through the language of its texts
      and its spokespersons. The way it is brought to people's attention will be the
      critical determinant of how they will respond to it. Currently, the discourse is
      based on metaphors of epicentres of spread identified as core transmitter groups.
      These are metaphors of distancing which encourage blame and denial. There are,
      however, within affected communities, new discourses emerging of inclusion,
      empowerment and processes and of the complexity of the reality of the epidemic.
      These discourses are associated with a new way of responding to the epidemic
      described here as one of community mobilization.

PMID- 7711089
TI  - Controlled evaluation of a brief intervention for HIV prevention among injecting
      drug users not in treatment.
AB  - This study evaluated the effectiveness of a brief intervention (BI), a one
      session motivational interview, in reducing HIV risk-taking behaviour among
      injecting drug users (IDU) not enrolled in any form of treatment for drug
      dependence. IDU were randomly assigned to either BI or a non-intervention control
      condition (NIC). One hundred and twenty-one subjects were successfully contacted
      for a 3-month follow-up and 88 subjects were followed up at 6 months. There were
      significant reductions for the sample as a whole for injecting risk-taking
      subscale scores on the HIV Risk-taking Behaviour Scale between pre-treatment and
      follow-up. There was no significant change in sexual risk-taking behaviour. There
      were no significant differences between groups on any measure at 3- and 6-month
      follow-up. There are a number of possible reasons why the sample as a whole
      showed significant improvements from initial to follow-up assessments. It is
      possible that, having had their attention directed to their risk-taking
      behaviour, subjects attempted to reduce their injecting risk-taking behaviour. If
      this is the case and subjects in the NIC condition can be considered as having
      received a BI, this suggests that BIs involving a personal risk assessment are
      effective in reducing risk behaviours associated with injecting. However, this
      suggestion could only be confirmed by comparison with a non-assessment control
      group.

PMID- 7711090
TI  - Volunteers in an HIV social care organization.
AB  - This study describes volunteers who were trained at a large HIV social care
      centre in South London during its first two years of operation. Many shared
      similar backgrounds to their clients; indeed some service users were also
      volunteers. Common motivations for volunteering were to learn more about HIV, to
      give something back to affected communities, and for gaining job-relevant
      experience. Selection, training and induction procedures were elaborate. But
      there were problems. Turnover was high, with half the volunteers dropping out in
      their first year. This matches reports for HIV organizations elsewhere, but is
      higher than for the voluntary sector in general. The high rate is attributed not
      to the nature of the work, but partly to the unusual social groups from whom
      volunteers are drawn and partly to the changing relationships between volunteers
      and the organization, symptomatic of which was loss of communication with staff
      and managers, and a consequent feeling of being undervalued. This can be linked
      to pressures arising from the pace of change in such organizations which have had
      the effect of marginalizing the role of volunteers. The new contractual
      arrangements with statutory agencies are contributing to the alienation, though
      ironically they were intended to strengthen the voluntary sector. The study
      questions whether AIDS service organizations should accept that the voluntaristic
      basis on which many originated is now over.

PMID- 7711091
TI  - Psychosexual problems in people with HIV infection: controlled study of gay men
      and men with haemophilia.
AB  - HIV infection can be associated with major psychological and social disturbance.
      Psychosexual problems would be expected to arise in the context of the infection,
      in view of the contribution that sexual behaviour can make to the acquisition and
      spread of HIV infection. Here the results of a study of the psychosexual
      consequences of HIV infection in gay men and men with haemophilia are presented,
      with the inclusion of data from control groups. Sixteen HIV-positive and 23 HIV
      negative gay men, and 20 HIV-positive and 24 HIV-negative men with haemophilia
      with sexual partners were studied. HIV infection was found to be associated with
      the greater risk of development of sexual dysfunction in seropositives, in
      particular in relation to ejaculatory difficulties, both delayed ejaculation in
      the case of gay men and men with haemophilia, and premature ejaculation in the
      case of men with haemophilia. Possible aetiological mechanisms are considered,
      including the possibility of organic disease. The findings are of relevance to
      those involved in the care of people with HIV infection.

PMID- 7711092
TI  - Condom use among criminally-involved adolescents.
AB  - Condom use was studied for 421 sexually active, minority male adolescents who
      were currently in jail in New York City. Over three-quarters of the youths were
      users of alcohol and marijuana and about one-quarter were users of cocaine or
      crack, but drug injectors were rare. In the six months before arrest they had
      multiple sexual partners and about one-third had engaged in anal intercourse.
      Inconsistent condom use was the norm, with 17% reporting that they never used
      condoms and only 15% reporting that they used condoms every time for insertive
      sex. In multivariate analysis, more frequent condom use was independently
      predicted by gay/bisexual preference, greater acceptability and accessibility of
      condoms, partners' receptivity to use, self-initiation of use, and self-efficacy
      of avoiding AIDS. Condoms were used less frequently with steady than with causual
      partners, and rarely for anal or oral sex. AIDS prevention curricula addressing
      these factors should be delivered to high risk adolescents while they are
      temporarily accessible in jail.

PMID- 7711093
TI  - A review of the HIV-related sexual behaviour of gay men and men who have sex with
      men.
AB  - In the last decade studies have identified a myriad of factors associated with
      continued risky sex in gay men and men who have sex with men. More recently the
      phenomenon of 'relapse' has been identified among this population. The results of
      such studies have been fed into the ongoing development of strategies to prevent
      HIV transmission. This paper critically examines this research--most of which is
      quantitative--and argues that the usefulness of the research is limited. Because
      of methodological problems, the evidence is contradictory and indeed, comparison
      across studies is almost impossible. An examination of the concept of 'relapse'
      illustrates the problems of relying on quantitative research which, in the main,
      removes individuals from their social context. The paper concludes that more
      qualitative research is required to locate individuals within their social milieu
      and to better understand them as individuals interacting with others and involved
      in an ongoing decision-making process about sexual pleasure and risk.

PMID- 7711094
TI  - WHO Global AIDS Statistics.

PMID- 7711095
TI  - Synthesis and evaluation of nuclear targeting peptide-antisense
      oligodeoxynucleotide conjugates.
AB  - An endogenous nuclear enzyme, RNase H, is an important component in determining
      the efficacy of antisense oligodeoxynucleotides (ODNs). In an effort to improve
      the potency of antisense ODNs, conjugates with three different nuclear targeting
      signal peptides were prepared. These short peptide sequences have been shown to
      facilitate transport of macromolecules into the nucleus of cells. Efficient
      chemistry for the synthesis of ODN-peptide conjugates is described. Reaction of
      5'-aminohexyl-modified ODNs with iodoacetic anhydride gave pure iodoacetamide
      ODNs (IA-ODNs) in good yield. These electrophilic intermediates were reacted with
      thiol-containing peptides to give ODN-peptides in excellent yield and purity. The
      ODN-peptides were further characterized by proteolysis with trypsin. Thermal
      denaturation studies with ssDNA targets showed little effect of the 5'-peptide
      modifications on the hybridization properties of the ODN. The effect of the
      nuclear signal peptides on antisense potency was evaluated in the freshwater
      ciliate Paramecium. A 3'-hexanol-modified 24-mer antisense ODN, complementary to
      the mRNA for calmodulin, alters regulation of membrane ion channels and swimming
      behavior of these cells. A 2'-O-methyl analog of this ODN was inactive, thus
      providing evidence that this activity in Paramecium is mediated by RNase H.
      Antisense ODN-nuclear signal peptide conjugates were transfected into the cells
      by electroporation. Surprisingly, these conjugates showed no antisense effects in
      comparison to a 5'-unmodified control ODN. Random peptides or amino acids
      conjugated to the 5'-terminus did not decrease antisense activity.

PMID- 7711096
TI  - Comparative photoaffinity labeling study between azidophenyl,
      difluoroazidophenyl, and tetrafluoroazidophenyl derivatives for the GABA-gated
      chloride channels.
AB  - Syntheses of 2-aryl-substituted photoactivatable derivatives of 5-tert-butyl-1,3
      dithiane and their oxidized bis-sulfone are described. The 4-azidoaryl and the
      3,5-difluoro-4-azidoaryl groups were chosen as photosensitive moieties. Azidoaryl
      derivatives 3 and 13 were synthesized by diazotization and azidation of their
      corresponding arylamine precursors. The o-difluoroazidophenyl derivatives 2 and 9
      were synthesized by transformation of the o-difluoro-substituted lithiophenyl
      into the corresponding azido derivative. The reversible binding properties of the
      photosensitive probes were established on bovine cortex P2 membranes by
      displacement of [3H]-1-phenyl-4-tert-butyl- 2,6,7-trioxabicyclo[2.2.2]-octane
      ([3H]TBOB), a specific ligand for the channel blocker binding site. The 2-(3',5'
      difluro-4'-azidophenyl)-5-tert-butyl- 1,3-dithianebis-sulfone, compound 2,
      exhibited the best Ki of about 11 nM, compared to Kis of 180 and 570 nM,
      respectively, for probes 1 (azidotetrafluorophenyl analogue) and compared to Kis
      of 180 and 570 nM, respectively, for probes 1 (azidotetrafluorophenyl analogue)
      and 3 (azidphenyl analogue). On irradiation, probe 2 (0.6 microM) produced 18%
      irreversible loss of TBOB binding sites in brain membranes while probe 3 did not
      produce any photoinactivation. The loss observed with 2 was fully protectable by
      TBOB, demonstrating the specificity of the photochemical inactivation by compound
      2 for the convulsant site of the GABAA receptor. These results, when compared to
      the photoaffinity labeling results obtained with the tetrafluorinated probe 1
      (25% selective irreversible photochemical inactivation), establish a hierarchy
      between fluorinated and nonfluorinated arylazido probes and strengthen the
      potential of the newly described difluorinated probe 2, combining high affinity
      and good labeling efficacy.

PMID- 7711097
TI  - Evaluation of a highly efficient aryl azide photoaffinity labeling reagent for
      the progesterone receptor.
AB  - 16 alpha,17 alpha-[(R)-1'-(4-Azidophenyl)ethylidenedioxy]pregn-4-ene- 3,20-dione
      (7) was prepared in high specific activity tritium-labeled form (20 Ci/mmol) and
      shown to bind to the progesterone receptor with an affinity (Kd = 0.80 nM) that
      is 47% of that of [3H]-R 5020 (Kd = 0.38 nM). [3H]Progestin aryl azide 7 exhibits
      high photoattachment efficiency (60% at 1 h) compared to the commonly used
      progesterone receptor photoaffinity labeling reagent [3H]-R 5020 (2.2% at 1 h)
      and is the most efficient progesterone receptor photoaffinity labeling reagent
      prepared to date. The photoattachment observed with 7 proceeds in a time
      dependent fashion, with most of the attachment occurring within the first 10 min
      of photolysis. Characterization of the photolabeled proteins by SDS
      polyacrylamide gel electrophoresis shows specific labeling of two adducts of
      molecular weight 108,500 +/- 800 and 87,000 +/- 1,500 (n = 3), the same species
      as labeled by [3H]-R 5020. The ratio of progesterone receptor subunits A:B was
      determined to be 3.3:1 with both [3H]progestin azide 7 and [3H]-R 5020.
      Information on the specific amino acid(s) that attach to the ligand during
      photolysis awaits further analysis of the covalently bound ligand-protein adduct.

PMID- 7711098
TI  - Mechanism of amide formation by carbodiimide for bioconjugation in aqueous media.
AB  - To study the mechanism of amide formation between carboxylic acid and amine in
      aqueous media using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride
      (EDC), hydrogels with two different types of carboxyl group locations were
      employed as substrates containing the carboxylic acid, while ethylenediamine and
      benzylamine were used as amine. In parallel, a study was undertaken with
      cyclizable carboxylic acids (maleic acid and poly(acrylic acid) and noncyclizable
      carboxylic acids (fumaric acid and poly(ethylene glycol) with the terminal
      carboxyl groups) to assess the reaction products by 13C-NMR and IR. EDC rapidly
      lost its activity in aqueous media of low pH, producing the corresponding urea
      derivative, but was very stable at neutral and higher pH regions. EDC could react
      with carboxyl groups at a relatively narrow low pH range such as 3.5-4.5. If
      carboxyl groups were cyclizable, they would react quickly with EDC producing
      carboxylic anhydrides, which formed the corresponding amides when amine compounds
      were present. On the other hand, a trace of amide was formed in the case of
      noncyclizable carboxylic acids. In addition, an excess of EDC caused an undesired
      side reaction to form stable N-acylurea, regardless of the special location of
      carboxylic acids.

PMID- 7711099
TI  - Galactose-containing amphiphiles prepared with a lipophilic radical initiator.
AB  - Novel amphiphiles which contain galactose residues (degree of polymerization (DP)
      = 6.2, 10, and 15) were prepared by telomerization of 2-[(methacryloyloxy)ethyl]
      beta-D-galactopyranoside using a lipophilic radical initiator. The galactose
      carrying amphiphile incorporated in a liposome was recognized by a lectin from
      Ricinus communis (RCA120), which was proven by the increase in turbidity of the
      liposome suspension after mixing with the lectin. The recognition was largely
      affected by the degree of polymerization and the surface density of the
      amphiphile. The amphiphile would be useful as a component of the drug delivery
      system to hepatocytes.

PMID- 7711100
TI  - Preparation of oligonucleotide-biotin conjugates with cleavable linkers.
AB  - A procedure is presented for preparing an oligonucleotide-biotin conjugate that
      is chemically cleavable through the reduction of a disulfide bond within the
      linker. Conjugation involves reaction of a primary amine with an N
      hydroxysulfosuccinimide ester linked to biotin. The oligonucleotide can be
      liberated from streptavidin agarose containing immobilized conjugate under mild
      conditions (neutral pH, 50 mM dithiothreitol). This cleavable conjugate is useful
      for affinity purification applications.

PMID- 7711101
TI  - Recombinant metallothionein-conjugated streptavidin labeled with 188Re and 99mTc.
AB  - Consideration is now being given to the use of avidin (or streptavidin) and
      biotin for radiotherapy of tumor. Accordingly, the goal of this study was to
      radiolabel a mouse metallothionein-streptavidin fusion protein with 188Re and to
      compare its properties to those of the same fusion protein radiolabeled with
      99mTc. A recombinant metallothionein-streptavidin fusion protein was radiolabeled
      by transchelation with 99mTc- and 188Re-glucoheptonate. Labeling efficiency,
      which was not optimized for either radionuclide, was approximately 60% for 99mTc
      and 20% for 188Re. Radiochemical purity was demonstrated by size exclusion HPLC
      both by nearly quantitative shifts of the 188Re label to higher molecular weight
      upon the addition of biotinylated antibody and by the absence of a shift with
      biotinsaturated 188Re-metallothionein-streptavidin. Stability of the labels in 37
      degrees C serum was evaluated by comparing the HPLC radiochromatograms of serum
      samples both before and after the addition of biotinylated antibody. The 188Re
      label behaved like 99mTc in that the same peaks were evident, including one
      prominent peak due to labeled cysteine. Recoveries during HPLC analysis of serum
      samples showed that oxidation rates to perrhenate and pertechnetate were
      identical. However, instability to cysteine challenge was greater for 188Re; for
      example, the loss of label to cysteine after 24 h under one set of conditions was
      41% for 188Re and 22% with 99mTc. Analysis by HPLC of liver and kidney
      homogenates from mice administered the labeled antibodies were qualitatively and,
      in large measure, quantitatively independent of label. Biodistributions at 5 h in
      normal mice were statistically identical between the two labels in blood and in
      most tissues. In conclusion, streptavidin may be radiolabeled with radiorhenium
      using recombinant mouse metallothionein as a bifunctional chelator, and under one
      set of labeling conditions at least, 188Re showed similar in vitro and in vivo
      behavior to that of 99mTc labeled to the same fusion protein.

PMID- 7711102
TI  - Synthesis of LHRH antagonists suitable for oral administration via the vitamin
      B12 uptake system.
AB  - Conjugates have been synthesized between vitamin B12 and two lysyl derivatives of
      the LHRH antagonist, ANTIDE. Lys6-ANTIDE and Lys8-ANTIDE were both found to have
      similar activities to the native analogue in the in vitro pituitary cell assay.
      The in vitro bioactivity of the VB12-ANTIDE conjugates was preserved following
      linkage using a number of spacers; however, the in vivo bioactivity was lost. In
      order to produce conjugates which had similar in vivo bioactivity to the native
      analogue, it was necessary to link the VB12 to the ANTIDE analogues using thiol
      cleavable spacers. The resultant conjugates had similar activity to ANTIDE both
      in vitro and in vivo and were also found to be much more water soluble than
      ANTIDE. These VB12-ANTIDE conjugates show potential utility as water soluble
      ANTIDE analogues for parenteral use and are protease resistant LHRH antagonist
      analogues suitable for uptake from the intestine via the VB12-transport system
      following oral administration.

PMID- 7711103
TI  - Preparation and characterization of antisense oligonucleotide-peptide hybrids
      containing viral fusion peptides.
AB  - We have developed a strategy for the synthesis of novel oligodeoxynucleotide
      (ODN)-peptide conjugates on a scale suitable for the investigation of their
      potential as antisense inhibitors of gene expression. These conjugates have the
      3'-terminus of the antisense oligodeoxynucleotide linked covalently to the N
      terminus of a peptide. This strategy allows the preparation of conjugates
      containing a peptide segment designed to facilitate intracellular delivery of the
      antisense oligodeoxynucleotide as well as providing protection against 3'
      exonuclease digestion. To illustrate the synthetic approach we describe the
      preparation of a series of conjugates comprising antisense oligonucleotides to
      human immunodeficiency virus type 1 (HIV) linked to fusion peptides derived from
      the HIV transmembrane glycoprotein gp41. The conjugates were prepared by the
      total synthesis method, in which the peptide is assembled first by the N
      (fluorenylmethoxycarbonyl) (Fmoc) solid-phase methodology. This is followed by
      derivatization of the amino terminus by reaction with an alpha,omega
      hydroxycarboxylic acid derivative which converts the terminus to a protected
      aliphatic hydroxy group on which standard solid phase DNA synthesis by the
      phosphoramidite method is performed. The purified conjugates were characterized
      extensively by several analytical techniques including ion spray mass
      spectrometry. Thermal denaturation studies showed that the interaction of the ODN
      peptide conjugate with its complementary strand was similar to that of unmodified
      oligonucleotides. Preparation by the total synthesis method gave the purified
      conjugate with overall yields in the range of 6-14%.

PMID- 7711104
TI  - Nucleosides and nucleotides. 135. DNA duplex and triplex formation and resistance
      to nucleolytic degradation of oligodeoxynucleotides containing syn-norspermidine
      at the 5-position of 2'-deoxyuridine.
AB  - A novel 2'-deoxyuridine analogue with syn-norspermidine at the 5-position, 5-[4
      [N,N-bis(3-amino-propyl)amino]butyl]-2'-deoxyuridine (1), has been synthesized
      from 5-iodo-2'-deoxyuridine. This nucleoside 1 was incorporated into
      heptadecadeoxynucleotides 5'-d[1(MT)8]-3' and 5'-[(TM)(4)1(MT)4]-3'(M = 5-methyl
      2'-deoxycytidine). The triamine group stabilized duplex and triplex formation of
      the heptadecadeoxynucleotides with a complementary strand and a target duplex,
      respectively. The oligonucleotides containing 1 were more resistant to nuclease
      P1 and snake venom phosphodiesterase than an unmodified heptadecadeoxynucleotide,
      5'-d[T(MT)8]-3'.

PMID- 7711105
TI  - A branched monomethoxypoly(ethylene glycol) for protein modification.
AB  - Procedures are described for linking monomethoxypoly(ethylene glycol) (mPEG) to
      both epsilon and alpha amino groups of lysine. The lysine carboxyl group can then
      be activated as a succinimidyl ester to obtain a new mPEG derivative (mPEG2
      COOSu) with improved properties for biotechnical applications. This branched
      reagent showed in some cases a lower reactivity toward protein amino groups than
      the linear mPEG from which it was derived. A comparison of mPEG- and mPEG2
      modified enzymes (ribonuclease, catalase, asparaginase, trypsin) was carried out
      for activity, pH and temperature stability, Km and Kcat values, and protection to
      proteolytic digestion. Most of the adducts from mPEG and mPEG2 modification
      presented similar activity and stability toward temperature change and pH change,
      although in a few cases mPEG2 modification was found to increase temperature
      stability and to widen the range of pH stability of the adducts. On the other
      hand, all of the enzymes modified with the branched polymer presented greater
      stability to proteolytic digestion relative to those modified with the linear
      mPEG. A further advantage of this branched mPEG lies in the possibility of a
      precise evaluation of the number of polymer molecules bound to the proteins; upon
      acid hydrolysis, each molecule of mPEG2 releases a molecule of lysine which can
      be detected by amino acid analysis. Finally, dimerization of mPEG by coupling to
      lysine provides a needed route to monofunctional PEGs of high molecular weight.

PMID- 7711106
TI  - DNA complexes with polycations for the delivery of genetic material into cells.

PMID- 7711107
TI  - Directed N-terminal elongation of unprotected peptides catalyzed by cathepsin C
      in water.
AB  - N-terminal chain extension of unprotected amino acid amides and peptides with
      dipeptide amides using Cathepsin C (dipeptidyl aminopeptidase I, EC 3.4.14.1)
      mediated reverse proteolysis in water was studied. Taking Pro-X-NH2 as the acyl
      donor, the sensitivity of the kinetically controlled peptide, coupling to pH
      value, temperature, acetonitrile addition, and nucleophile type were
      investigated. Basic or hydrophobic amino acids as the alpha-amino-N-nucleophile
      proved to be much more prone to catalyzed bond formation than their neutral,
      hydrophilic, or negatively charged analogues. In a preparative run a pentapeptide
      was obtained with 83% yield by directed and regioselective coupling of ProTrpNH2
      with LysLeuPheNH2 catalyzed by Cathepsin C in aqueous buffer.

PMID- 7711108
TI  - Fluorinated o-aminophenol derivatives for measurement of intracellular pH.
AB  - The simple 2-aminophenol group which serves as a building block for many cationic
      indicators has been modified to yield a series of pH sensitive probes. This
      approach is based on the replacement of one of the N-acetate groups of the
      chelator APTRA (o-aminophenol N,N,O-triacetate) by an N-ethyl group. The
      resulting series of (N-ethylamino)phenol (NEAP) compounds exhibit pK values in
      the physiological range and negligible affinity for physiological levels of other
      ions. Three fluorinated analogs have been prepared: N-ethyl-5-fluoro-2
      aminophenol N,O-diacetate (5F NEAP), N-ethyl-2-((2-fluoro-4-carboxybenzyl)oxy)-4
      fluoroaniline-N- acetic acid (5F NEAP-2), and 1-(2-(N-ethylamino)-5
      fluorophenoxy)-2-(2-fluoro-4- aminophenoxy)ethane-N,N',N'-triacetic acid (5F NEAP
      3). These derivatives exhibit total titration shifts of approximately 11 ppm.
      NEAP-2 and NEAP-3 contain an additional fluorine to serve as an internal chemical
      shift reference, and NEAP-3, the most highly charged analog prepared, was
      designed in order to minimize leakage.

PMID- 7711109
TI  - A novel minor groove binding reagent designed to serve as a "truck" to carry DNA
      modifying moieties into the major groove.
AB  - A site selective DNA minor groove binding tripyrrole peptide has been synthesized
      as a "truck" to place chemical functionalities into the major groove which are
      capable of physically modifying DNA, acting as catalysts to hydrolyze DNA, or
      effectively protecting DNA from various DNA modifying enzymes. The equilibrium
      dissociation constants for the binding of this peptide to an A3T3 dsDNA binding
      site have been determined to be nanomolar, and they are compared to the constants
      for other minor groove binding agents.

PMID- 7711110
TI  - Intensely luminescent immunoreactive conjugates of proteins and dipicolinate
      based polymeric Tb (III) chelates.
AB  - Partial alkylation of polylysine with 4-(iodoacetamido)-2,6-dimethylpyridine
      dicarboxylate (IADP), followed by exhaustive reaction with succinic anhydride,
      yielded polymers (PLDS, polymer of lysine, dipicolinate, and succinate)
      containing large numbers (50-100) of 4-substituted dipicolinic acid moieties per
      molecule, with the remaining lysyl side chains succinylated. Competition
      experiments showed that PLDS binds Tb(III) ions with much higher affinity than
      does EDTA and strongly enhances the visible luminescence they emit when excited
      with ultraviolet light. Carbodiimide-mediated coupling to proteins, including
      bovine serum albumin, ovalbumin, and protein A, yielded PLDS-protein conjugates
      whose Tb(III) chelates displayed intense green luminescence and millisecond
      excited state lifetimes. These conjugates retained sufficient immunoreactivity to
      allow their use in sensitive luminescence-based immunodetection schemes for
      proteins immobilized on nitrocellulose. The presence of 10 ng of ovalbumin could
      be easily visualized by eye when probed with rabbit anti-ovalbumin and PLDS
      protein A-Tb(III). The ease of preparation of PLDS-protein-Tb(III) conjugates,
      and their favorable luminescence properties, make them promising reagents for use
      in time-resolved luminescence immunoassays and other ultrasensitive detection
      schemes for macromolecules.

PMID- 7711111
TI  - Strand invasion by oligonucleotide--nuclease conjugates.
AB  - Conjugates consisting of staphylococcal nuclease crosslinked to oligonucleotides
      hybridize to supercoiled duplex DNA by Watson--Crick base-pairing. Here we
      describe this strand invasion. Affinity cleavage by these conjugates provides a
      probe for the local topology of the DNA duplex and is most efficient at a target
      DNA sequence known to form a cruciform. Additional supercoiling of the substrate
      DNA increases selective cleavage at other sequences. Hybridization of the
      conjugate to duplex DNA is temperature dependent and is stable over time.
      Affinity cleavage is not substantially inhibited by a 200-fold excess of the
      analogous unmodified oligonucleotide, demonstrating that hybridization of the
      unmodified oligonucleotide must be less favored and that the nuclease is involved
      in substrate binding. Surprisingly, affinity cleavage is also not effectively
      inhibited by complementary oligonucleotides unless they contain an extended 5'
      sequence capable of separate interactions with the nuclease domain of the
      conjugate. These results suggest that the oligonucleotide-nuclease conjugate
      prefers to hybridize to target sequences which will allow interactions with both
      the oligonucleotide and the nuclease domains. Affinity cleavage by
      oligonucleotide-nuclease conjugates provides general insights for the design of
      oligonucleotides and their conjugates for strand invasion and affords a
      convenient competition assay for their hybridization.

PMID- 7711112
TI  - SV40-induced immortalization of human cells.
AB  - For several decades simian virus 40 (SV40) early region genes have been used as a
      means of generating immortalized human cell lines; however, the molecular
      mechanisms of this process have begun to be understood only recently. SV40
      induced immortalization proceeds via two phases. In the first phase ("lifespan
      extension"), cells continue proliferating for a limited number of population
      doublings beyond the point at which normal cells undergo senescence. This is
      mainly due to the ability of SV40 large T antigen (LTAg) to bind to the protein
      products of the p53 and retinoblastoma (Rb) genes. The second phase
      ("immortalization") occurs in only a small minority of cells, and cell
      hybridization analyses indicate that this is a gene inactivation event. The gene
      or genes involved are currently unknown, but chromosomal localization data are
      accumulating which should make their cloning and characterization possible in the
      near future.

PMID- 7711113
TI  - Retrodifferentiation and cell death.
AB  - The reversibility of a differentiation program termed dedifferentiation,
      redifferentiation, or retrodifferentiation opens a spectrum of new possibilities
      for cellular development. During differentiation and retrodifferentiation, the
      expression of gene products associated with a differentiated phenotype and cell
      cycle regulation demonstrate inverse patterns. This effect requires a coordinated
      network that simultaneously controls cell growth and differentiation. In
      particular, crosstalk between induction of differentiation and G0/G1 cell cycle
      exit can be initiated and sustained by activated serine/threonine kinases and
      tyrosine kinases. Phosphorylation signals are relayed to certain genes or
      transcription factors such as Fos/Jun, EGR-1, NF-kappa B, MyoD, or the Myc/Max
      gene family. However, the precise regulation of these transcription factors to
      confer signals to differentiation-associated and cell cycle-regulatory genes
      remains unclear. Cell cycle exit into a transient G0'-arrest cycle or a terminal
      G0 phase is determined by a network of phosphorylation signals involving the
      retinoblastoma protein and a variety of factors such as the E2F family, cyclins,
      and cyclin-dependent kinases. In this context, a variety of differentiation
      induced cell lines, including monocytic, neuronal, or muscle cells, can progress
      through the G0'-arrest cycle, whereby a certain population retains the capacity
      to retrodifferentiate and reenter the cell cycle. In contrast, the rest of the
      differentiated population enters the irreversible G0 phase (terminal commitment)
      that finally results in programmed cell death. The expression of growth arrest
      specific (gas and gadd) genes is associated with the G0'-arrest cycle, and other
      factors, including c-myc, p53, mdm2, and bcl2/bclx, contribute to the regulation
      of the cell death program. Although the precise signaling cascade determining
      retrodifferentiation or cell death remains unclear, a coordinated inter- and
      intracellular regulation could establish a certain biological balance between
      these exclusive pathways. Consequently, a retrodifferentiation process may
      provide a potential for cell type conversion or transdifferentiation, whereby
      retrodifferentiated cells can be induced to develop via a different pathway
      according to tissue-specific requirements.

PMID- 7711114
TI  - The role of Myb proteins in normal and neoplastic cell proliferation.
AB  - The c-myb protooncogene is the prototype of a gene family that contains two other
      recently described members, A-myb and B-myb. The c-myb gene encodes a
      transcription regulatory protein, c-Myb, that has distinct DNA-binding domain
      structure and binding specificity compared with unrelated transcription factors.
      All three members of the myb protein family, however, display a high degree of
      homology within their DNA-binding domain, suggesting that they may regulate
      transcription of a similar set of target genes. We examine here whether, by
      implication, the individual members of the myb gene family play analogous roles
      within the cell, in particular focusing on their potential functions in the
      control of cell proliferation. Expression of both c-myb and B-myb is subject to
      regulation in the cell cycle, transcripts of these genes being induced within the
      G1 phase of the cell cycle and persisting at maximal levels through S phase.
      Consistent with this timing of expression, inhibition of c-Myb and B-Myb
      synthesis by treatment of cells with anti-sense oligonucleotides indicates that
      both proteins are required for transition from the G1 to S phase of the cell
      cycle. The c-Myb and B-Myb proteins cannot be considered as analogs, however, as
      they show certain differences in trans-activation activity of their target genes.
      Moreover, while superficially similar, expression of c-myb and B-myb is not
      coordinated, and it is conceivable that their products have quite distinct
      functions in the regulation of cell proliferation. The ubiquitous expression of B
      myb in cycling cells and its strict regulation during late G1 suggest a universal
      function for B-Myb in G1 to S phase transition. Consistent with this conclusion,
      B-myb transcription is controlled by the transcription factor E2F, which has been
      implicated in cell cycle regulation of a number of genes involved in DNA
      synthesis. The restricted tissue tropism of c-myb expression and its regulation
      by certain growth factors such as IL-2 suggest a specific function in
      transduction of extrinsic proliferation (and differentiation) signals. The role
      of A-myb in the cell remains to be determined; however, its expression shows no
      correlation with cell cycling, implying that it has no direct role in cell
      proliferation. Recent data show that the necessity for c-myb function in
      proliferation of a number of cell types provides a promising opportunity for
      intervention in the treatment of certain tumors.

PMID- 7711115
TI  - Tissue-specific transformation by oncogenic mutants of epidermal growth factor
      receptor.
AB  - Mutations in the receptor for the epidermal growth factor provide valuable
      insight into mechanisms of growth control. Oncogenic mutants of this receptor
      tyrosine kinase cause erythroid leukemia, fibrosarcoma, angiosarcoma,
      glioblastoma, and melanoma. Mutations in the avian protooncogene occur by
      retroviral mechanisms. Deletion of the ligand-binding domain results in
      erythroblastosis, while additional mutations in cytoplasmic structures broaden
      the disease potential to other cell types. A carboxyl-terminal structure of erbB
      oncogenes modulates growth responses in a complex, cell-specific manner; this
      tissue-specificity region appears to promote growth in erythroblasts and to
      produce trans-dominant inhibition in fibroblasts. Human glioblastoma multiforme
      frequently contains receptor mutations that are reminiscent of avian oncogenes.
      In hereditary melanoma of Xiphophorus, aberrant regulation of transcription by a
      recombinant promoter determines tissue-specific tumorigenesis. The diversity of
      oncogenic mutations raises important questions concerning the roles of several
      receptor structures. The extracellular domain inhibits the receptor when
      unoccupied by ligand, for example, through a mechanism that is unknown. The auto
      phosphorylation sites are dispensable for transformation, so their function in
      neoplastic growth is unclear. The carboxyl-terminal region promotes or blocks
      transformation in different tissues, suggesting complex regulation by unknown
      cellular factors. These issues are critical to understanding of the mechanisms of
      receptor activation and tissue tropism for this family of oncogenes.

PMID- 7711116
TI  - [Usefulness of pharmacokinetic and pharmacodynamic parameters fro establishing
      the optimal dosage of antibacterials].

PMID- 7711117
TI  - [Infections in neutropenic patients].

PMID- 7711118
TI  - [Eyelash mite infestation].

PMID- 7711119
TI  - [Multisite tuberculous spondylitis as a presentation of miliary tuberculosis].

PMID- 7711120
TI  - [Pleural empyema caused by Haemophilus influenzae associated with active pleural
      and pulmonary tuberculosis].

PMID- 7711121
TI  - [Detection of imipenem resistance in a strain of Campylobacter jejuni isolated
      from feces of a boy with diarrhea].

PMID- 7711122
TI  - [Should we look for Hantavirus infection in Spanish patients?].

PMID- 7711123
TI  - [Tuberculous splenic abscesses in AIDS].

PMID- 7711124
TI  - [Bacteremic pneumonia caused by Neisseria meningitidis in an elderly patient].

PMID- 7711125
TI  - [Endocarditis caused by Gemella haemolysans with formation of a perivalvular
      abscess].

PMID- 7711126
TI  - [Disseminated herpes zoster with pneumonitis in an HIV-positive patient].

PMID- 7711127
TI  - [Myonecrosis caused by Aeromonas].

PMID- 7711128
TI  - [Acute retinal necrosis caused by varicella zoster virus].

PMID- 7711130
TI  - [Visceral leishmaniasis in patients with HIV infection].
AB  - BACKGROUND: Visceral leishmaniasis (VL) is an endemic parasitosis in Spain with a
      frequency which is increasing, specially among those patients with HIV infection.
      METHODS: The clinical characteristics of 36 episodes of VL in 20 patients with
      HIV infection diagnosed in the authors' center from January 1988 to October 1993
      are herein described. The appearance of recurrences and mortality rate were
      analyzed with survival curves. RESULTS: The most frequently observed findings
      were constitutional syndrome (92%), fever (67%), splenomegaly (86%), hepatomegaly
      (80%) and hematologic changes (100%) with the symptoms being of longer duration
      in the initial episodes than in the recurrences. In 97% of the patients the CD4+
      lymphocyte count was lower than 200 x 10(6)/l, with greater immunosuppression
      observed during the recurrences. Serology (IFI) was positive in 25% of the
      patients. Microscopic examination of bone marrow aspirate demonstrated the
      presence of Leishmania amastigotes in 82% of the initial episodes and in all the
      recurrences. Neither the bone marrow biopsy nor the culture improved this
      performance. Less than 10% of the episodes were recurrence free at 12 months of
      evolution with allopurinol prophylaxis not being useful. Mortality directly
      attributable to VL was nul and the survival curve showed a worse prognosis for
      patients who had a diagnosis of AIDS previously or simultaneously to the
      presentation of VL. CONCLUSIONS: The clinical manifestations of visceral
      leishmaniasis in patients with HIV infection are similar to those presented by
      non immunosuppressed patients. The serology is little sensitive for diagnosis and
      the exploration of choice is the microscopic examination of the bone marrow
      aspirate. The prognosis of acute infection is good but the frequency of
      recurrence is high. The authors believe that visceral Leishmaniasis should be
      considered as a diagnostic criteria for AIDS.

PMID- 7711129
TI  - [Drugs: piperacillin/tazobactam].

PMID- 7711131
TI  - [Presentation, diagnosis and treatment of pyogenic liver abscess: analysis of a
      series of 63 cases].
AB  - BACKGROUND: The aim of this study was to know the clinical, etiopathogenic and
      microbiologic characteristics of pyogenic liver abscesses (PLA). METHODS: A
      retrospective analysis of the cases of PLA diagnosed from 1978 to 1992 in the
      Internal Medicine, Infectious Disease, and Gastrointestinal Surgery Departments
      of the Hospital de Bellvitge in Barcelona, Spain was performed. RESULTS: A total
      of 63 cases of PLA (43 males and 20 females, mean age 54 +/- 19 years) were
      analyzed. The most frequent clinical and analytical data included fever (92%),
      leucocytosis (84%) and abnormal levels of alkaline phosphatase (81%). The PLA
      were single in 65% and multiple in 35%. Echography was diagnostic in 91% of the
      cases. A positive culture of the abscess was obtained in 40 cases, being
      monomicrobial in 27 cases (67.5%). Eleven of the 13 polymicrobial cultures were
      from single PLA. The most frequent bacteria found were the enterobacteria (44%)
      followed by the microaerophilic streptococci (28%) and the anaerobes (17%). The
      PLA was of biliary origin in 31.8%, contiguous in 12.7% and unknown in 38%.
      Percutaneous drainage was performed in 34 patients (54%). Mortality attributable
      to the abscess was 3%. CONCLUSIONS: The clinical presentation of pyogenic liver
      abscess has not varied over time. There has, however, been a change with respect
      to its epidemiology and therapeutic management. At present, the possibility of
      rapid diagnosis and image guided percutaneous drainage offers a better prognosis
      for this disease.

PMID- 7711132
TI  - [Importance of anaerobic bacteria in recurrent childhood non-streptococcal
      tonsillitis].
AB  - BACKGROUND: The presence of anaerobes in the oropharyngeal flora was already
      known, but they were infrequently involved in infections, except for specific
      diseases (abscesses, Vincent's angina). The involvement of anaerobes in more
      frequent by observed oropharyngeal diseases has been recently proposed. METHODS:
      We analyzed the tonsillar flora of 22 healthy children (control group) and 54
      children diagnosed of recurrent tonsillitis. We compare the clinical response of
      children with recurrent tonsillitis to two treatments: penicillin, and penicillin
      plus metronidazole. RESULTS: We isolated Streptococcus pyogenes from 22.2% of
      children with tonsillitis, and did not isolate it from any healthy children. The
      rest of tonsillar flora was qualitatively similar in both groups. Both
      populations showed a high proportion of beta-lactamase-producer bacteria. In
      children from whom S. pyogenes was isolated, the response to the treatment was
      similar for both treatments. In those cases where S. pyogenes was not isolated,
      penicillin + metronidazole cured the 77.2% of children treated, but penicillin
      cured only 30% of cases. CONCLUSIONS: These results suggest that anaerobes might
      be involved, at least, in recurrent tonsillitis when S. pyogenes is not found,
      and justify further studies about the etiology and treatment of this disease.

PMID- 7711133
TI  - [False sensitivity of Enterococcus faecium to amoxicillin-clavulanic acid with
      the MicroScan system].
AB  - BACKGROUND: We have observed by using MicroScan automatic system discrepancies in
      susceptibility results of Enterococcus faecium strains to ampicillin and
      amoxicillin/clavulanic acid. METHODS AND RESULTS: Seventy-six strains of E.
      faecium were studied with MicroScan; 98.7% of them were inhibited by 16 mg/l of
      amoxycillin-clavulanic acid versus 60.5% inhibited by the same concentration of
      ampicillin. We have evaluated the susceptibility to ampicillin, amoxicillin and
      amoxicillin-clavulanic acid of 7 strains of E. faecium by both MicroScan and
      standard microdilution assay. MIC values of ampicillin were similar by both
      methods but MIC values of amoxicillin/clavulanic acid obtained by MicroScan (< or
      = 4/2 mg/l in 6 strains) were considerably lower than those obtained by standard
      microdilution (> or = 16/8 in 6 strains). This phenomenon was not dependent of
      betalactamase production or bacterial inocula. CONCLUSIONS: When using MicroScan,
      E. faecium strains resistant to ampicillin (betalactamase non producers) must be
      also considered resistant to amoxicillin/clavulanic acid without considering the
      values obtained by this system.

PMID- 7711134
TI  - [Osteoarticular infections caused by Streptococcus agalactiae. Report of 4
      cases].
AB  - BACKGROUND: Streptococcus agalactiae (group B streptococcus) is a rare etiology
      of osteoarticular infection in adults. In a literature review (Medline-Embase
      plus) up until may 1994, we have found only 51 cases. In most patients, diabetes
      mellitus, liver disease or long-term steroid therapy were documented. METHODS:
      Four adult patients with osteoarticular infection due to S. agalactiae from two
      Galician hospitals were studied from January 1988 to October 1994: prepatellar
      bursitis (one case), septic monoarthritis (2 cases) and psoas abscess associated
      to cervical spondylodiscitis and oligoarthritis (left sternoclavicular and left
      hip joints). RESULTS: In the first patient, a young woman with prepatellar
      bursitis, a previous local trauma was recorded. The second case, a man with
      septic arthritis of right knee, had degenerative disease of the knees and a
      prostatic adenocarcinoma. In the third patient, a diabetic woman with septic
      arthritis of the left shoulder, vulvovaginitis due to Candida albicans was found.
      The last patient suffered vertebral osteomyelitis of the cervical spine (C3-C4),
      arthritis of the left sternoclavicular and hip joints and abscess of the
      ipsilateral psoas. The evolution was favourable in the four cases. CONCLUSIONS:
      Although uncommon, osteomyelitis and arthritis caused by group B streptococcus
      should be considered as opportunistic pathogen in adults with debilitating
      conditions. Early recognition and prompt institution of adequate therapy can help
      avoid joint destruction and severe complications.

PMID- 7711135
TI  - Genetics and heavenly intervention.

PMID- 7711136
TI  - High-efficiency gene transfer to autologous rabbit jugular vein grafts using
      adenovirus-transferrin/polylysine-DNA complexes.
AB  - Within the first year, 15-20% of coronary artery saphenous bypass vein grafts
      (SVGs) occlude because of thrombosis or progressive intimal hyperplasia. One
      potential new strategy to reduce this complication would be to introduce
      antithrombotic or antiproliferative genes in vein grafts before implantation. The
      success of this approach requires an efficient DNA delivery system. In the
      present study we tested the feasibility of using adenovirus
      transferrin/polylysine-DNA complexes (TfAdpl/DNA) to achieve high-efficiency gene
      transfer into vascular interposition vein grafts. All studies used the
      Escherichia coli LacZ (beta-galactosidase [beta-Gal]) reporter gene under the
      control of the cytomegalovirus (CMV) earlier promoter and enhancer (pCMV/LacZ).
      Autologous rabbit jugular vein segments were incubated ex vivo for 60 min in a
      solution of TfAdpl/DNA complexes (1.2 x 10(10) biotinylated adenovirus particles,
      2,430 ng of streptavindylated polylysine. 10 micrograms of plasmid DNA, and 9
      micrograms of transferrin-polylysine per ml), and then reimplanted across the
      ligated right carotid artery. Control veins were incubated in TfAdpl solution in
      which DNA was omitted. A total of six grafts were treated with TfAdpl/DNA, and
      two grafts were treated with TfAdpl. Veins were harvested 3 (n = 3) and 7 (n = 3)
      days later and beta-Gal activity was determined by X-Gal chromogen staining. All
      six TfAdpl/DNA-treated grafts stained intensely blue, whereas control grafts were
      negative. Microscopic examination of serial sections revealed intracellular blue
      granules consistent with beta-Gal activity to be present in all of the
      endothelial cells and in numerous medial and advential cells.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7711137
TI  - Delivery of a secretable adenosine deaminase through microcapsules--a novel
      approach to somatic gene therapy.
AB  - Many current gene therapy protocols require genetic modification of autologous
      cells. An alternate approach is to use universal recombinant cell lines
      engineered to secrete in vivo the desired gene products. Enclosing these cells
      within immunoprotective devices before implantation would prevent rejection of
      the nonautologous donor cells. To overcome the limitation that not all
      therapeutic gene products are secreted, we now propose to fuse a signal sequence
      to the amino terminus of a nonsecreted protein such as human adenosine deaminase
      (ADA), thus directing the product into a secretory pathway for release from the
      cells. A fusion gene constructed between the cDNA of the beta-lactamase signal
      sequence and human ADA expressed a product after in vitro transcription and
      translation that was immunologically similar to the human protein. Mouse
      fibroblasts transfected with the fusion gene demonstrated secreted ADA activity
      that resembled the human cytosolic enzyme in its heat stability, pH optimum, KM,
      electrophoretic mobility, and immunologic reactivity. Hence, the secreted enzyme
      expressed from the fusion gene is antigenically and enzymatically similar to the
      authentic human form. When transfected mouse fibroblasts or myoblasts were
      enclosed in permselective alginate-poly-L-lysine alginate microcapsules, ADA
      activity was secreted from the microcapsules and the cells remained viable for
      over 5 months. Hence, a secretable and functional human ADA has been constructed
      that can be delivered from recombinant cells within immunoprotective capsules.
      The success of this strategy provides the prototype for engineering nonsecreted
      gene products for therapy via this novel method of somatic gene therapy.

PMID- 7711138
TI  - Consequences of stable transduction and antigen-inducible expression of the human
      interleukin-7 gene on tetanus-toxoid-specific T cells.
AB  - Interleukin-7 (IL-7) has previously been shown to increase antigen-specific
      immune responses; the effect of IL-7 on human antigen-specific T cell lines has
      not directly been addressed. A tetanus-toxoid (TT)-specific T cell line exhibited
      increased proliferation in the presence of exogenous IL-7, suggesting that IL-7
      may be useful in the potentiation of immune responses to defined microbial
      antigens. Murine retroviral vectors encoding the human IL-7 gene and the neomycin
      phosphotransferase gene (neoR) were packaged into murine retroviral particles,
      and supernatants containing these retroviral vectors were used to infect a CD4+
      lymphoblastoid cell line. Stable integration of the retroviral vector and
      constitutive expression of the IL-7 gene were observed. Successful IL-7 gene
      transduction into TT-specific T cells was also accomplished. Detection of neoR
      DNA sequences and expression of IL-7-specific mRNA increased with selection in
      geneticin. Production of IL-7 in these cells was induced by exposure to TT.
      Production of IL-4, IL-6, and interferon-gamma (IFN-gamma) was detected after
      antigenic stimulation; there was, however, no effect of IL-7 on the pattern or
      kinetics of cytokine production by these cells. Human IL-7 transduced cells
      showed greater proliferation to TT than control T cells, particularly at
      subthreshold TT concentrations. These dta imply that genetic modification of
      antigen-specific T cells may be a plausible strategy for the study and
      manipulation of the immune responses to microbial pathogens.

PMID- 7711139
TI  - Inhibition of human immunodeficiency virus type-1 by retroviral vectors
      expressing antisense-TAR.
AB  - The human immunodeficiency virus type-1 (HIV-1) Tat activation response (TAR)
      region is essential for Tat-mediated trans-activation of the HIV-1 long terminal
      repeat (LTR). The TAR element is present on the 5' and 3' ends of all HIV-1
      transcripts and is relatively conserved among different HIV-1 isolates. These
      properties make it an attractive target for anti-HIV-1 gene therapy strategies.
      We have constructed a Moloney murine leukemia-based retroviral vector that
      expresses a chimeric tRNA(iMet)-antisense TAR fusion transcript complementary to
      the HIV-1 TAR region. The potential of this anti-TAR retroviral vector to inhibit
      HIV-1 was initially tested by transient transfections with an HIV-1-LTR-Tat
      expression plasmid into HeLa-CAT cells. Anti-TAR inhibited Tat-mediated HIV-1 LTR
      driven CAT reporter gene expression in a dose-dependent fashion. The antisense
      TAR vector was then used to transduce the human SupT1 T cell line. Cotransfection
      of these SupT1 cells with a Tat expression plasmid plus an HIV-1 LTR-CAT reporter
      plasmid resulted in decreased CAT gene expression in comparison to control
      transduced SupT1 cells. The antisense-TAR engineered SupT1 cell line was then
      challenged with HIV-1MN.HIV-1 viral production was inhibited in SupT1 cells
      transduced with the antisense-TAR retroviral vector. Greater inhibition of HIV-1
      was observed with antisense-TAR as compared to antisense-Tat expressing
      retroviral vector. These observations suggest that antisense-TAR retroviral
      vectors are potentially useful for clinical anti-HIV-1 gene therapy.

PMID- 7711140
TI  - Gene expression following direct injection of DNA into liver.
AB  - The liver is an attractive target tissue for gene therapy. Current approaches for
      hepatic gene delivery include retroviral and adenoviral vectors, liposome/DNA,
      and peptide/DNA complexes. This study describes a technique for direct injection
      of DNA into liver that led to significant gene expression. Gene expression was
      characterized in both rats and cats following injection of plasmid DNA encoding
      several different proteins. Luciferase activity was measured after injection of
      plasmid DNA encoding the luciferase gene (pCMVL), beta-galactosidase (beta-Gal)
      activity was evaluated in situ using plasmid DNA encoding Lac Z (pCMV beta), and
      serum concentration of secreted human alpha-1-antitrypsin was measured following
      injection of plasmid DNA encoding this protein (pRC/CMV-sHAT). Several variables,
      including injection technique, DNA dose, and DNA diluent, were investigated.
      Direct injection of pCMVL resulted in maximal luciferase expression at 24-48 hr.
      beta-Gal staining demonstrated that the majority of transfected hepatocytes were
      located near the injection site. Significant concentrations of human alpha-1
      antitrypsin were detected in the serum of animals injected with pRC/CMV-sHAT.
      These findings demonstrate the general principle that direct injection of plasmid
      DNA into liver can lead to significant gene expression.

PMID- 7711141
TI  - Emergence of early region 1-containing replication-competent adenovirus in stocks
      of replication-defective adenovirus recombinants (delta E1 + delta E3) during
      multiple passages in 293 cells.
AB  - Early region 1 (E1)-deleted human adenovirus (AV) recombinants have been shown to
      be powerful tools of gene transfer in vivo and in vitro and are considered for
      application in human gene therapy. We could detect increasing titers of E1
      containing adenovirus in two independent E1 + E3-deleted recombinant AV stocks
      during multiple passages in 293 cells, most likely due to a recombinant event
      with the host cell genome. We show the deleterious effects of this E1-containing,
      mostly replication-competent AV subpopulation in vivo and compare different
      screening methods of AV stocks for its detection. These considerations are
      important for the safety of human gene therapy trials.

PMID- 7711142
TI  - Construction and characterization of retroviral vectors expressing biologically
      active human interleukin-12.
AB  - Interleukin-12 (IL-12) is a heterodimeric cytokine originally defined by its
      ability to induce the maturation of cytolytic lymphocytes and by its capacity to
      effectively synergize with IL-2 in the induction of cytolytic activity. Recent
      studies in mice have demonstrated the ability of IL-12 to cause tumor regression
      and stimulate long-term antitumor immunity in treated animals. To examine the
      antitumor effect of direct gene transfer of IL-12 into tumors, we have developed
      retroviral vectors that coordinately express both subunits of IL-12. An MFG-based
      retroviral vector was used to generate a recombinant retrovirus in which a long
      terminal repeat (LTR)-driven polycistronic transcript encodes both subunits of
      human IL-12: hp35 and hp40 cDNAs are linked and coexpressed using the internal
      ribosome entry site (IRES) from the encephalomyocarditis virus (DFG-hIL-12). In
      addition, two IRES sequences were used to express both subunits of IL-12 and a
      neomycin resistance (neoR) selectable marker gene from the same polycistronic
      message (TFG-hIL-12). The amphotropic DFG-hIL-12 and TFG-hIL-12 viruses were used
      to infect both human and murine cell lines as well as primary tumor cultures. The
      production of human IL-12 by the nonselected, infected cells was measured in both
      a PHA blast proliferation bioassay and an ELISA and ranged from 15 to 40 ng/10(6)
      cells per 24 hr. Following G418 selection of TFG-hIL-12-infected cells, the level
      of expression of IL-12 was significantly higher (up to 120 ng/10(6) cells per 24
      hr). The IL-12 protein secreted by the infected cells exhibited all of the
      biologic activities of recombinant hIL-12: proliferation of activated natural
      killer (NK) and T cells, stimulation of interferon-gamma (IFN-gamma) induction by
      NK and T cells, and enhancement of lymphokine-activated killer (LAK) activity.
      These retroviral vectors expressing human IL-12 should be useful in evaluating
      the biological properties of IL-12 as well as for use in clinical trials for gene
      therapy of patients with cancer.

PMID- 7711143
TI  - Use of safety-modified retroviruses to introduce chemotherapy resistance
      sequences into normal hematopoietic cells for chemoprotection during the therapy
      of ovarian cancer: a pilot trial.

PMID- 7711144
TI  - Study on contribution of genetically marked peripheral blood repopulating cells
      to hematopoietic reconstitution after transplantation.

PMID- 7711145
TI  - Biological response modifiers in the small bowel allograft rejection.
AB  - Immunological response is an interlinking network of stimuli and response
      signals. Rejection includes a complex series of events that depends on the
      interaction of many cells and soluble mediators--cytokines--and other biological
      response modifiers--among these, prostaglandins and hormones. In small bowel
      transplantation rejection, the role of "biological response modifiers" may be
      especially important because cytokines act on both "antigens presenting cells"
      from the recipient and "passenger lymphocytes" from the donor, in addition
      cytokines play a central role in the pathogenesis of clinical acute graft versus
      host disease. Finally, perspective of new modalities of immunosuppression appear
      to be important in monitoring and controlling the cytokine release and function.

PMID- 7711147
TI  - [Enteral nutrition in ICU patients on a high-protein diet].
AB  - BASIS: The need for nutritional support is at present beyond question, while the
      use of early enteral nutrition in critical patients admitted to Intensive Care
      Units is increasingly common and would appear to offer a set of advantages as
      nutritional support. PATIENTS: Of a total of 26 consecutive enteral nutrition
      patients, 22 were studied prospectively (84.6%), and, through a nasal-gastric
      probe, were administered early high protein enteral polymeric diet with 25% of
      total calorific value from proteins, for an average of 10 days. The other four
      (15.4%) did not enter the study, according to the exclusion criteria established,
      and so were not taken into account in the statistics. METHOD: A design was
      followed in which the diet was administered progressively until reaching 30
      ml/kg/day, in a maximum of three days, during which aspects were analyzed dealing
      with tolerance and ease of use, on the one hand, and other metabolic and
      nutritional aspects on the other. Analytical controls were carried out on days 0,
      4, 8 and 12. Tolerance and adverse effects were monitored continuously. RESULTS:
      During the study, one of the twenty-two patients died (4.54%): the other 21
      remained alive. In analysis of the metabolic and nutritional parameters,
      improvement was obtained in all those expected to reach normal levels, with p <
      0.001 (glucose, prealbumin, TF, RBP, Zn, Mg and P). Of particular note was the
      evolution of the nitrogen balance (p < 0.001 and r = 0.77). As to tolerance,
      diarrhea appeared in two patients (9.09%), ileus in one (4.5%): no cases were
      detected of abdominal distension, nausea or vomiting. In no case was diet
      suspended for causes attributable to the enteral nutrition, nor was any
      therapeutic manipulation required. CONCLUSIONS: Excellent tolerance of enteral
      nutrition was obtained, with almost no complications associated with its use,
      despite the gravity of the patients (APACHE 14). On the other hand, an
      improvement was obtained in metabolic and nutritional parameters, with the
      particular significance of the nitrogen balance.

PMID- 7711146
TI  - Enhancement of fatty acid mobilization and oxidation by glucose-xylitol compared
      to glucose alone in posttraumatic and septic patients.
AB  - INTRODUCTION: The objective of this study was to provide further information
      about the influence of xylitol on glucose and fatty acid metabolism after trauma
      and during sepsis. METHODS: In study I 18 metabolically normal patients
      undergoing coronary artery bypass grafting operation were randomly assigned into
      three groups. Group I (C I, n = 6) received 2 mg/kgBW/min of glucose, group II (C
      II, n = 6) 2 mg/kgBW/min of a glucose/xylitol mixture (1:1) and group III (C III,
      n = 6) 1 ml/kgBW/min of an isotonic saline solution. Infusions were applied over
      a 24-h-period following operation. Concentrations of glucose, lactate, insulin
      and single free fatty acids were measured before and after surgery and at 6-h
      intervals over 36 hours postoperatively. In study II 5 septic patients were
      intravenously given 4 mg/kgBW/min glucose over a 6-h-period. Energy supply was
      then changed to a glucose/xylitol (1:1) regimen in an equicaloric dosage of 4
      mg/kgBW/min for six hours again. Hepatic glucose production ([6,6-d2]-glucose),
      palmitate oxidation ([1-13C]-palmitate) and lactate concentrations were analyzed
      at the end of each infusion regime with the help of stable isotope technique and
      an enzymatic test, respectively. RESULTS: In study I glucose and insulin
      concentrations in C II and III were significantly lower than in C I during the
      postoperative infusion period. Highest lactate concentrations were measured in C
      I after 6 hours of infusion. Free fatty acids in C I remained at significantly
      lower levels compared to C II and III until glucose infusion was stopped. In
      septic patients (study II) xylitol led to significant lower hepatic glucose
      production rates and lactate concentrations than glucose, whereas palmitate
      oxidation increased. CONCLUSIONS: During the acute phase after trauma and during
      sepsis a carbohydrate supplementation with xylitol was superior to glucose alone
      because high plasma glucose concentrations were avoided, highly energy consuming
      hepatic glucose production was reduced and the release and oxidative utilization
      of free fatty acids was enhanced.

PMID- 7711148
TI  - [The usefulness of cholesterol as a nutritional-metabolic marker in the septic
      patient].
AB  - We studied the behavior of the cholesterol of 118 septic patients on entering
      Intensive Care and on receiving parenteral nutritional support, to establish its
      utility as malnutrition and/or monitoring marker. On admission, there was more
      intensive hypocholesterolemia (104 +/- 39 mg/dl) in those who had developed multi
      organ failure (87 +/- 34 mg/dl, p < 0.001). There was no correlation between
      cholesterol and gravity (APACHE II). Basal cholesterol values were correlated
      with transferrin (r = 0.58), prealbumin (r = 0.43), retinol-linked protein (r =
      0.32) and albumin (r = 0.32) and albumin (r = 0.54). During twelve days'
      parenteral nutrition, cholesterol and visceral protein levels recovered, and the
      good correlation was maintained between cholesterol and transferrin while that
      between cholesterol and prealbumin increased and that between cholesterol and
      retinol-linked virtually disappeared. There ceased to be a relation between
      albumin and cholesterol as from day six. In cases where the septic situation was
      maintained, with clinical deterioration, cholesterol levels did not rise. This,
      along with the close correlation with transferrin, led us to think that
      cholesterol is influenced by inflammation mediators, acting as a marker for this
      more as nutritional parameter. However, in practice, it provides the same
      information as short-life visceral proteins, and its determination is more
      accessible.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711149
TI  - [An analysis of an enteral nutrition guideline in patients with cancer of the ORL
      area].
AB  - AIMS: The result was assessed of the enteral nutrition guideline prescribed in 50
      patients using internationally accepted parameters as indicators of the
      nutritional state. METHODS: Fifty patients were selected at random with an ORL
      zone neoplasm, they were prescribed enteral nutrition according to our Section's
      procedure, involving the administration of a commercialized enteral diet whose
      composition is a homogenization of natural foods administered in 6 sessions at
      three-hour intervals during the day, begun with 100 cc of diet per session up to
      a total of 400 (2400 kcal/day), and with the addition of 100 cm of water in each
      administration. The average age was 59.58 +/- 11.2 years (range 30-81), the
      average duration of nutrition was 34.02 +/- 32.1 days (range, 3-201 days). The
      following were taken in all cases: Weight (W), Size (S), Tricipital fold (TF),
      brachial circumference, urinary creatinin, seric albumin (A), seric transferrin
      (T), total lymphocytes (Lt) and retarded cutaneous sensitivity, using Multitest
      IMC (M), and these data were used to calculate muscular circumference (MC) and
      the creatinin size index (CSI). Two nutritional valuations (NV) were analyzed,
      the first one taken (NV1) and the one prior to discharge (V2). Analytical
      calculations were done by our Center's Analytical Laboratory. We used Wilcoxon's
      test included in the SX statistical package for statistical analysis. RESULTS: On
      the fifty patients selected, only thirty had a second NV. Comparison of the two
      calculations gave the following results: A statistically significant rise of A
      (A1: 3.6 +/- 0.8, vs A: 3.8 +/- 0.7; p < 0.0001) and of T (T1: 208.2 +/- 52.0, vs
      T2: 237.5 +/- 44.39; p < 0.0001). There was also a statistically significant
      reduction of P (P1: 63.93 +/- 12.32 vs P2: 62.88 +/- 11.28; p < 0.04). Comparison
      of the remaining variables did not provide statistically significant differences:
      PT (PT1: 11.46 +/- 4.9 vs PT2: 12.07 +/- 4.6; p > 0.05). MC (MC1: 23.93 +/- 2.5
      vs MC2: 23.58 +/- 1.9; P > 0.05). CSI (CSI1: 8.5 +/- 8 vs CSI2: 6.9 +/- 2.9; p >
      0.05). L (L1: 1855 +/- 760.5 vs L2: 1808 +/- 769.1; p > 0.05). M (M1: 12.58 +/-
      7.8 vs M2: 14.01 +/- 8.5; p > 0.05). CONCLUSIONS: It is deduced from the results
      that the guideline used is useful in maintaining the nutritional state of
      patients prior to their treatment, despite weight-loss, since the ratio of weight
      loss to the time between NV1 and NV2 is not significant.

PMID- 7711150
TI  - [The assessment and nutritional support of patients with the acquired
      immunodeficiency syndrome].
AB  - Given the negative effect of malnutrition on the immune function, the possibility
      must be considered that this also affects the clinical progression of AIDS
      patients. This study was aimed at assessing the state and nutritional support
      indicated for patients diagnosed as having AIDS. 114 patients admitted to our
      hospital in the period 1990-1991 were studied, with assessment of the nutritional
      state by means of anthropometric parameters (weight, size, tricipital fold, arm
      muscle circumference), biochemical parameters (albumin, lymphocytes, transferrin,
      RBP) and the treatment prescribed. Average age was 31.44 +/- years, 81.5% were
      male, 68% parenteral drug addicts. 71% had a stage IV C diagnosis. 37.72% had
      diarrhea before beginning treatment. The malnutrition diagnosed was as follows:
      moderate, 50.89%, severe 36%, slight, 12.5%, and mixed (calorific-protein),
      62.5%, calorific 34.8%, and protein 2.6% of cases, 33% of the patients received
      dietary supplements, 33.84% enteral alimentation and 33% parenteral alimentation.
      Nutritional support was suspended as follows: improvement, 54.46%; transfers,
      1.79%; death, 27.68%, and terminal situation, 16.07%. Deceased or terminal
      patients were more severely malnourished (p < 0.001) than the remainder. AIDS
      patients are studied and treated nutritionally in a very advanced stage of the
      illness, with severe malnutrition which conditions a poorer evolutive diagnosis.
      This suggests a change of attitude, with assessment being necessary of
      nutritional state and the appropriate therapy at the time of diagnosis, in order
      to slow the progression of the illness.

PMID- 7711151
TI  - [Food consumption and the nutritional status of schoolchildren of the Community
      of Madrid (CAENPE): general methodology and overall food consumption. Consumo de
      alimentos y estado nutricional de la poblacion escolar].
AB  - The CAENPE study (Food Consumption and Nutritional State of the School
      Population) was a transversal observational study funded and promoted by the
      Directorate-General of Food Hygiene in the Ministry of Health, implemented in
      1991-93, with the main aim of quantifying food consumption in the school
      population (6-14 years of age) in the Regional Community of Madrid, together with
      an anthropometric study and nutritional analysis of that population. This project
      sets our the General Methodology for the study, paying particular attention to
      the sampling design, to ensure that the sample is representative of the
      community, and the results of the overall consumption of food and its comparison
      with recommended diet and other population studies. Quantification shows a high
      and rising consumption of meat, meat products, sweets, snacks and prepared
      dishes, suitable consumption of eggs, legumes and fruit and a notable lack of
      greens, vegetables and potatoes. The basic results underline the need to
      introduce educational measures with practical effect on home and school menus.

PMID- 7711152
TI  - [The assessment of the nutritional status of patients with familial amyloid
      neuropathy type I (Corino Andrade's disease) who are candidates for orthotopic
      liver transplantation].
AB  - Corino Andrade's disease (Type I Family amyloidotic polyneuropathy) (FAP I) is a
      slow-evolving hereditary amyloidosis affecting, among other things, the digestive
      system, with the appearance of an amyloid deposit which produces a malabsorptive
      syndrome with diarrhea in those affected. At present, the only effective
      therapeutic option is orthotopic liver transplant (OLT): clearance from the
      hospital's transplant commission as a candidate requires, among other things, a
      prior nutritional study. We therefore proposed to carry out a nutritional
      assessment of these patients, comparing them with a group of terminal liver
      patients who are OLT candidates. The PAF I group showed a high level of calorie
      energy malnutrition (86%) and, to a lesser extent, visceral and protein
      malnutrition. The liver patient group showed 67% of visceral malnutrition and
      lower levels of calorific energy and protein malnutrition. All the OLT candidates
      showed a high rate of nutritional deterioration. The greater presence of
      calorific energy malnutrition in the PAF I patients might be due to the
      neuropathic gastro-intestinal condition. The high level of malnutrition
      encountered suggest the need for pre-transplant nutritional intervention designed
      to minimise post-surgical risk.

PMID- 7711153
TI  - Hypocaloric peripheral parenteral nutrition.

PMID- 7711154
TI  - [Anthropometric studies in Spain].

PMID- 7711155
TI  - [Fat-rich diets in patients with mild chronic obstructive lung disease (COPD)].
AB  - A study was made in stable patients suffering from mild COLD of the maximum
      capacity for ergometric cycle exercise and gas exchange at rest and during
      maximum exercise, measured by indirect calorimetry. During the period of study (3
      months) one group of patients receive the usual diet while the other received an
      oral nutritional supplement rich in fats an minimum of 75% of their energy
      expenditure measured at rest. The patients studied, with mild COLD, were
      hypermetabolic, and although at rest they presented indirect calorimetry data
      such as would correspond to similar subjects, during exercise not just the limit
      on exercise became clear but also the alteration to ventilatory capacity and gas
      exchange. The fat-rich nutritional supplement administered for three months did
      not succeed in enhancing exercise capacity or in altering gas exchange during
      maximum exercise is stable patients with mild COLD.

PMID- 7711156
TI  - XVth Annual Conference on Peritoneal Dialysis. Baltimore, Maryland, February 12
      14, 1995. Abstracts.

PMID- 7711157
TI  - Primary structure of the serotonin transporter in unipolar depression and bipolar
      disorder.
AB  - Genetic factors have been implicated in the etiology of affective disorders but
      due to the complex inheritance patterns of these disorders, identification of the
      responsible gene(s) has so far been unsuccessful. Decreased platelet serotonin (5
      HT) transport and reduced binding of imipramine or paroxetine to brain and
      platelet 5-HT uptake sites/transporters in patients with depression and suicide
      victims define the 5-HT transporter (5-HTT) as a candidate gene. The primary
      structure of the 5-HTT was analyzed in 17 patients meeting DSM-III-R diagnostic
      criteria for major depressive or bipolar disorder and in 4 healthy controls using
      polymerase chain reaction (PCR-) amplification and sequencing of complementary
      deoxyribose nucleic acid (cDNA) synthesized from platelet 5-HTT messenger ribose
      nucleic acid (mRNA). Direct PCR sequencing of the protein coding region failed to
      reveal changes in the deduced amino acid sequence of the platelet/brain 5-HTT
      (40,000 base pairs sequence screened), although a conservative single-base
      substitution representing a silent polymorphism was found. The results provide
      preliminary evidence that alterations in the primary structure of 5-HTT are not
      generally involved in the pathogenesis of unipolar depression and manic
      depressive illness.

PMID- 7711158
TI  - [3H]paroxetine binding to platelets of patients with social phobia: comparison to
      patients with panic disorder and healthy volunteers.
AB  - Recent studies suggest that serotonergic functioning may be aberrant in patients
      with social phobia. Capacity of the serotonin (5-HT) transporter, as determined
      by 3H-paroxetine binding, was measured in 18 drug-free patients with generalized
      social phobia and compared to 15 drug-free patients with panic disorder and 23
      healthy control subjects. The density (Bmax) and affinity (1/Kd) of 3H-paroxetine
      binding sites was similar in all three groups. To the extent that the serotonin
      transporter in platelets and neurons is comparable, these findings suggest that
      this aspect of serotonergic function is normal in patients with social phobia.

PMID- 7711159
TI  - Basal and haloperidol-stimulated prolactin and symptoms of nonaffective and
      affective psychoses in neuroleptic-free men.
AB  - The prolactin (PRL) response to 0.5 mg of intravenous haloperidol (HPL) IV may be
      a measure of tuberoinfundibular dopaminergic activity. Our earlier reports, using
      multidiagnostic strategies in schizophrenia, suggested that psychoses
      characterized by the absence of affective syndromes (Keks et al 1990) and the
      presence of thought disorder and passivity delusions (Keks et al 1992) are linked
      to blunted PRL responses. In this paper we evaluated the relationships between
      basal and HPL-stimulated PRL concentrations, and a number of potentially relevant
      symptom measures. Basal PRL was lower in patients without a depressive syndrome
      and suicidal ideation. Stimulated PRL was lower in patients without
      neurovegetative symptoms (versus patients with neurovegetative symptoms and
      controls), with depression (versus patients with no depression and controls) and
      those with disorder of associations (versus patients without association
      disturbance and controls). These findings can be interpreted as indicating a link
      between endocrine measures of dopaminergic function and a subtype of
      schizophrenic psychosis characterized by the presence of thinking disturbance in
      the absence of depression.

PMID- 7711160
TI  - The Na,K-ATPase hypothesis for bipolar illness.
AB  - A cellular model for bipolar illness is presented. It is propounded that
      alterations in the activity of the membrane sodium- and potassium-activated
      adenosine triphosphatase pump (Na,K-ATPase) may be responsible for alterations in
      neuronal excitability and activity. Specifically, a reduction in Na,K-ATPase
      activity can lead to both mania and depression by increasing membrane
      excitability and decreasing neurotransmitter release, respectively. Supporting
      evidence is reviewed, and clinical and research implications are discussed.

PMID- 7711161
TI  - Neuroendocrine responses to d-fenfluramine and insulin-induced hypoglycemia in
      chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) is a disorder characterized by severe physical and
      mental fatigue and fatiguability of central rather than peripheral origin. We
      hypothesized that CFS is mediated by changes in hypothalamopituitary function and
      so measured the adrenocorticotrophic hormone (ACTH), cortisol, growth hormone,
      and prolactin responses to insulin-induced hypoglycemia, and the ACTH, cortisol,
      and prolactin responses to serotoninergic stimulation with dexfenfluramine in
      nondepressed CFS patients and normal controls. We have shown attenuated prolactin
      responses to hypoglycemia in CFS. There was also a greater ACTH response and
      higher peak ACTH concentrations (36.44 +/- 4.45 versus 25.60 +/- 2.78 pg ml),
      whereas cortisol responses did not differ, findings that are compatible with
      impaired adrenal cortical function. This study provided evidence for both
      pituitary and adrenal cortical impairment in CFS and further studies are merited
      to both confirm and determine more precisely their neurobiological basis so that
      rational treatments can be evolved.

PMID- 7711162
TI  - Concordant factors of depression rating scales and dimensionality of depression.
AB  - A redundancy analysis was carried out between a doctor rating scale (D-RS) and a
      patient self-rating scale (P-SRS) to determine relating dimensions. The first and
      second major redundancy variates obtained from the P-SRS and the D-RS were
      rotated to obtain biorthogonality and interpretability. The obtained two
      concordant dimensions between the P-SRS and the D-RS were interpreted as
      depression and vegetative factors. Any redundancy factors before the rotations,
      however, did not reveal a general factor pattern. These results suggest that the
      two-dimensional structure is more appropriate for understanding the depression
      symptomatology rather than the unidimensional structure of a general or
      endogenous factor pattern. We also discussed how dimensional differences caused a
      low concordance in severity or total scores.

PMID- 7711163
TI  - Muscarinic receptors on human eccrine sweat gland in aging and Alzheimer's
      disease.
AB  - Age and Alzheimer's disease-related changes have been reported in the peripheral
      cholinergic system controlling sweating. We present (1) evidence of a high
      affinity muscarinic receptor localized on human eccrine sweat gland and (2)
      muscarinic receptor concentrations on eccrine gland samples from 22 patients with
      probable Alzheimer's disease of various degrees of dementia, 8 age-matched
      controls, and 11 young controls. Muscarinic receptors were measured using
      autoradiography with 3H-NMS as ligand. We found no evidence of changes related to
      aging or Alzheimer's disease in the overall concentration of receptors or in the
      amount of gland showing binding. Nor was there any correlation between the degree
      of dementia as measured by the Global Deterioration Scale or the Mini-Mental
      State Exam and 3H-NMS binding. In conclusion, we find no evidence that previously
      reported sweat gland functional changes associated with aging and Alzheimer's
      disease are reflected in changes in eccrine gland muscarinic receptor density.

PMID- 7711164
TI  - Relationship between smooth pursuit eye-tracking and cognitive performance in
      schizophrenia.
AB  - The relationship between measures of smooth pursuit and neuropsychological
      performance was assessed in 20 unmedicated schizophrenics. Eye-tracking measures
      included gain, catch-up saccade parameters, and rate of saccadic intrusions.
      Neuropsychological measures included tests generally considered as "frontal":
      Wisconsin Card Sorting Test (WCST), Consonant Trigram Test (CTT), and Controlled
      Oral Word Association Test (COWAT). The Digit Symbol Test (DST), which is
      generally considered to be a measure of global functioning, was also included.
      Gain and other pursuit measures were significantly correlated with the DST and
      the COWAT, but were not correlated with the WCST or the CTT.

PMID- 7711165
TI  - The dexamethasone suppression test in violent suicide attempters with major
      depression.

PMID- 7711166
TI  - Visual field defects in psychiatric disorders: possible genetic implications.

PMID- 7711167
TI  - Parietal scalp hair whorl patterns in schizophrenia.

PMID- 7711168
TI  - Prediction of response to total sleep deprivation by autonomic heart rate
      parameters?

PMID- 7711169
TI  - Location of the PH-20 protein on acrosome-intact and acrosome-reacted spermatozoa
      of cynomolgus macaques.
AB  - Fluorescence microscopy and transmission electron microscopy (TEM) were used to
      determine the location of the membrane protein PH-20 on spermatozoa of cynomolgus
      macaques. Rabbit antiserum raised against recombinant cynomolgus macaque sperm PH
      20 was used as the primary antibody, and the second antibody was goat anti-rabbit
      IgG conjugated with either fluorescein isothiocyanate or 15 nm gold particles.
      Spermatozoa were evaluated before capacitation and after capacitation and
      induction of acrosome reactions with calcium ionophore A23187. In sperm
      suspensions with a high percentage of intact acrosomes, fluorescence labeling was
      observed uniformly over most of the sperm head. The sperm midpiece and tail were
      not labeled. In sperm suspensions with a high percentage of acrosome reactions,
      most spermatozoa labeled intensely over the anterior sperm head, but labeling of
      the posterior sperm head was greatly reduced. TEM of acrosome-intact spermatozoa
      revealed gold particles distributed uniformly on the plasma membrane overlying
      the acrosome, the equatorial segment, and most of the post-acrosomal region.
      After the acrosome reaction, gold label was present on the inner acrosomal
      membrane and on the plasma membrane overlying the equatorial segment. Very little
      label was present on the plasma membrane in the post-acrosomal region of acrosome
      reacted spermatozoa. The location of PH-20 on the surface of macaque spermatozoa
      suggests a function for this protein in primary and/or secondary binding to the
      zona pellucida. The apparent decrease in amount of PH-20 on the posterior head of
      macaque spermatozoa following the acrosome reaction is consistent with the
      migration of this protein to the inner acrosomal membrane, as demonstrated
      previously for the homologous PH-20 protein of guinea pig spermatozoa.

PMID- 7711170
TI  - Porcine calbindin-D9k gene: expression in endometrium, myometrium, and placenta
      in the absence of a functional estrogen response element in intron A.
AB  - The expression of Calbindin-D9k (CaBP-9k) in the pig uterus and placenta was
      measured by Northern blot analysis and reverse transcription polymerase chain
      reaction (PCR), respectively. Progesterone (P4) administration to ovariectomized
      pigs decreased CaBP-9k mRNA levels. Expression of endometrial CaBP-9k mRNA was
      high on pregnancy Days 10-12 and below the detection limit on Days 15 and 18. On
      Day 60, expression could be detected at low levels. In myometrium and placenta,
      CaBP-9k mRNA expression was not detectable by Northern analysis using total RNA.
      Reverse-transcribed RNA from both tissues demonstrated the presence of CaBP-9k
      transcripts by means of PCR. The partial CaBP-9k gene was amplified by PCR and
      cloned to determine the sequence of intron A. In contrast to the rat CaBP-9k
      gene, the pig gene does not contain a functional estrogen response element (ERE)
      within this region. A similar ERE-like sequence located at the identical location
      was examined by gel retardation analysis and failed to bind the estradiol
      receptor. A similar disruption of this ERE-like sequence has been described in
      the human CaBP-9k gene, which is not expressed at any level in placenta,
      myometrium, or endometrium. It is concluded that the pig CaBP-9k gene is
      regulated in these reproductive tissues in a manner distinct from that in rat and
      human tissues. The regulation is probably due to a regulatory region outside of
      intron A, which in the rat gene contains the key cis element for uterine
      expression of the CaBP-9k gene.

PMID- 7711171
TI  - Cellular and molecular mechanisms that mediate insulin-dependent rat granulosa
      cell mitosis.
AB  - Rat ovarian follicles are composed of small and large granulosa cells (GC). The
      present studies demonstrate that small GCs undergo insulin- or phorbol ester
      dependent mitosis in vitro. In order to examine the cellular and molecular events
      that account for insulin's mitogenic action, small GCs were cultured with either
      insulin, phorbol ester (TPA), or both insulin and TPA. Insulin and TPA increased
      GC numbers by 21 +/- 3% and 20 +/- 2% over control values, respectively (p <
      0.05). Simultaneous addition of insulin and TPA increased GC numbers by 20 +/- 3%
      (p < 0.05). In a second experiment, small GCs were exposed to control medium,
      insulin, staurosporine (a protein kinase C [PKC] inhibitor), or both insulin and
      staurosporine. These studies revealed that insulin induced a 21 +/- 5% increase
      in GC numbers and that staurosporine blocked insulin's mitogenic action. These
      observations suggest that insulin mediates its mitogenic action through a PKC
      dependent mechanism. Since the proto-oncogenes, c-fos and c-jun, are expressed
      during GC mitosis, studies were undertaken to determine whether or not the
      expression of these two proto-oncogenes products was enhanced by insulin. The
      expression of c-fos and c-jun proteins was assessed by immunocytochemistry. These
      studies showed that after 5 h, insulin increased the percentage of cells that
      stained for c-fos and c-jun by 15 +/- 2% and 19 +/- 4, respectively (p < 0.05).
      The expression of these proto-oncogenes was blocked by staurosporine. Both
      progesterone and 8-br-cAMP, which block insulin-dependent GC mitosis, also
      inhibited the expression of c-fos and c-jun.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711172
TI  - Counter current transfer of oxytocin from the venous blood of the perihypophyseal
      cavernous sinus to the arterial blood of carotid rete supplying the hypophysis
      and brain depends on the phase of the estrous cycle in pigs.
AB  - The objective of the present study was to determine whether or not the
      neuropeptide, oxytocin, can move by counter current transfer from venous blood of
      the perihypophyseal cavernous sinus into arterial blood of the carotid rete
      supplying the brain and hypophysis, and also whether this exchange depends on the
      day of the estrous cycle. Isolated heads of gilts (n = 37), on different days of
      the estrous cycle, were supplied with autologous, oxygenated and heated blood at
      a stable blood flow and pressure through the right carotid artery for 30 min.
      125I-Oxytocin (125I-OT) was infused into both cavernous sinuses through the
      angularis oculi veins for 5 min. After 125I-OT infusion, radiolabeled oxytocin
      was found in arterial blood taken from the carotid rete in all 7 gilts on Days 1
      3, and in 7 of 9 gilts on Days 12-13 of the estrous cycle. In general, the level
      of radioactivity in arterial blood during Days 12-13 was significantly lower (p <
      0.002) than during Days 1-3 of the estrous cycle. No 125I-OT was found in
      arterial blood from Days 4 through 11 (n = 10) or from Day 14 to the beginning of
      ovulation (n = 11). These results provide evidence for the counter current
      transfer of oxytocin from hypophyseal and brain venous effluent (cavernous sinus)
      to arterial blood supplying the hypophysis and brain, during the ovulation period
      and the late luteal phase of the estrous cycle. The meaning of this process is
      not as yet known and needs further study.

PMID- 7711173
TI  - Maternal dietary glucose-lipid interactions modulate embryological development in
      vivo and in embryo culture.
AB  - To examine the dietary interrelationships of glucose and lipid on embryological
      growth and development, two levels of glucose (0% and 24%) and two types of lipid
      -soybean oil (SBO; 44.5% 18:2[n-6]) or oleic acid (OL; 6.7% 18:2[n-6])--were fed
      to pregnant rat dams until Day 12.5 of gestation, when developing embryos and
      maternal tissues were collected for analysis. In addition, Day 9.5 embryos were
      obtained from the dietary treatment groups and cultured in vitro until Day 12.5
      to ascertain whether or not the embryos showed developmental changes in response
      to dietary treatment in the absence of maternal and placental factors.
      Differences in energy intake and macronutrient composition explained differences
      in early placental weight; macronutrient composition, but not energy intake,
      accounted for differences in weight of in vivo embryos and in morphological
      scores of cultured embryos. With food intake as a covariate in the statistical
      analysis, the results showed that only the level of maternal dietary glucose
      influenced the number of live embryos and resorptions per litter. Both the level
      of carbohydrate and the type of lipid in the maternal diet, however,
      independently and interactively affected both embryonic growth and development in
      vivo and in culture. To evaluate the biological significance of this dietary
      interaction, concentrations of essential fatty acids in the embryonic and
      maternal tissues were measured. A striking result of this study was the rapidity
      of the diet-induced changes in tissue fatty acid composition. By gestational Day
      12.5, the lack of glucose in the OL-based diet was associated with a raised 18:2
      (n-6)/20:4 (n-6) ratio and a lowered 20:4 (n-6) content in the embryo and the
      maternal liver. We suggest that a carbohydrate-free maternal diet with apparently
      adequate levels of essential fatty acid can contribute to embryonic growth
      retardation both in vivo and in vitro by perturbing embryonic essential fatty
      acid metabolism.

PMID- 7711174
TI  - Fertilizing ability of bovine spermatozoa cocultured with oviduct epithelial
      cells.
AB  - The effects of bovine oviduct epithelial cell monolayers (OECM), derived from the
      different segments of the oviduct and under various conditions, on oocyte
      penetration by bovine sperm were determined by in vitro cell culture techniques.
      The oocyte penetration rate by sperm treated with OECM+OECM-conditioned medium
      was 93% (155 of 166). Sperm penetration rates in OECM+fresh medium and in OECM
      conditioned medium alone were 66% (115 of 173) and 52% (87 of 167), respectively,
      significantly lower (p < 0.01) than in OECM+OECM-conditioned medium. However, the
      percentage of penetrated oocytes in OECM-conditioned medium alone was
      significantly higher than in control (11% = 16 of 148; p < 0.01). In both the
      OECM+OECM-conditioned medium and the OECM+fresh medium groups, oocyte penetration
      rates by sperm cocultured with OECM derived from the isthmic segment were
      significantly lower than those by sperm cocultured with OECM derived from the
      ampullary segment (44% = 43 of 98 vs. 72% = 68 of 94, and 42% = 49 of 117 vs. 66%
      = 72 of 110, respectively; p < 0.01). Sperm penetration rates were low after
      insemination in the OECM-conditioned medium alone derived from either the isthmic
      or the ampullary segments (20% = 20 of 100 and 19% = 17 of 91, respectively).
      However, the sperm penetration rate was improved significantly when OECM
      conditioned medium was obtained from whole-oviduct OECM (57% = 60 of 105; p <
      0.01). The effect of OECM derived from different segments on ability of sperm
      binding and maintaining motility was also evaluated in vitro.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7711175
TI  - Prenatal androgens modify the reproductive response to photoperiod in the
      developing sheep.
AB  - In most seasonal breeders, photoperiod influences the timing of the transition to
      sexual maturity. In sheep, males and females express reproductive maturity under
      different photoperiods. Spring-born males begin the maturational process during
      lengthening days (spring), whereas females do so during shortening days (autumn).
      We hypothesized that photoperiod differentially influences the transition to
      sexual maturity in each sex, and that this difference results from the presence
      or absence of androgens prenatally. We monitored the timing of sexual maturity in
      male and female lambs (n = 8 each) and in prenatally masculinized female lambs (n
      = 7) maintained under controlled photoperiods (natural-simulate or reverse
      natural-simulate). Circulating LH was analyzed to reveal the timing of the
      pubertal gonadotropin rise; lambs were gonadectomized and implanted with
      estradiol to provide a constant feedback on LH secretion. Under natural-simulate
      photoperiod, LH increased in males at 7.0 +/- 0.3 wk when days were lengthening.
      In females treated similarly, sexual maturity occurred at 27.0 +/- 0.8 wk when
      day lengths were decreasing. The reverse photoperiod had no effect on males, but
      it delayed the expression of sexual maturity in females. Thus, LH also increased
      in males at 7.1 +/- 0.9 wk, while none of the females maintained under the same
      photoperiod had elevated LH secretion when the experiment was terminated (32 wk
      of age). Prenatal treatment with androgens masculinized the reproductive response
      to photoperiod; as in the males, LH increased in the androgenized females
      maintained under a reverse natural-simulate photoperiod at 7.1 +/- 0.4
      wk.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711176
TI  - Rescue of pregnancy and maintenance of corpora lutea in infertile transgenic mice
      expressing an ovine metallothionein 1a-ovine growth hormone fusion gene.
AB  - Transgenic female mice expressing a temporally regulatable ovine metallothionein
      1a-ovine growth hormone (oMT1a-oGH) fusion gene can cycle, mate, and support
      early embryonic development; but they fail to maintain pregnancy or, in most
      cases, to exhibit signs of pseudopregnancy. The present study was designed to
      determine whether or not the infertility of oMT1a-oGH transgenic female mice is
      due to luteal insufficiency. A series of five experiments was conducted in which
      various hormonal therapies were utilized in an attempt to overcome this
      infertility. Provision of 1 mg progesterone to oMT1a-oGH females from Days 1 to
      17 of gestation rescued pregnancy in 19 of 20 females with an increased mean
      litter size (p < 0.01) compared to that of wild-type control females.
      Supplementation with progesterone also appeared on the basis of gross anatomical
      appearance to maintain CI. Provision of 2 mg progesterone in combination with 25
      ng estradiol-17 beta from Days 4 to 17 rescued pregnancy in 14 of 24 oMT1a-oGH
      females, while provision of 100 or 25 micrograms ovine prolactin from Days 3 to
      17 failed to overcome oMT1a-oGH infertility. Transgenic females with rescued
      pregnancies lactated and raised heavier pups than wild-type females by Day 15
      postnatal (p < 0.05). Results indicate that infertility of oMT1a-oGH transgenic
      mice is caused by luteal insufficiency. Supplementation of transgenic females
      with progesterone appeared to maintain morphologically normal CL and pregnancy
      with subsequently increased litter size and normal lactation.

PMID- 7711177
TI  - Increased egg production by active immunization against vasoactive intestinal
      peptide in the turkey (Meleagris gallopavo).
AB  - Vasoactive intestinal peptide (VIP) is a hypothalamic prolactin (PRL)-releasing
      factor in the turkey. The hypothesis in the present study was that active
      immunization of turkeys with VIP would neutralize endogenous VIP, decrease
      circulating PRI, and consequently prevent the expression of incubation behavior.
      Large white female turkeys were divided into three experimental groups comprising
      untreated controls, control turkeys immunized with keyhole limpet hemocyanin
      (KLH), and turkeys immunized with synthetic chicken VIP conjugate (KLH-cVIP).
      Each turkey received four injections at 4-wk intervals, starting on the day of
      photostimulation. The immune response, measured by the percentage binding of
      monoiodinated chicken VIP (cVIP) to plasma at a dilution of 1:1000, averaged 11.8
      +/- 2.5% during the reproductive life cycle. Immunization against KLH-cVIP
      prevented the normal increases of PRL that are associated with the photo-induced
      reproductive cycle. Over a 21-wk period beginning at photostimulation, KLH-cVIP
      immunized birds exhibited a maximal plasma PRL level of 82.2 +/- 29.5 ng/ml,
      compared to 367.7 +/- 66.6 ng/ml and 227.5 +/- 51.7 ng/ml for non- and KLH
      immunized turkeys, respectively. The total number of nest visits per hen during
      the 147-day experimental period decreased from 320.0 +/- 48.2 in the nonimmunized
      controls to 180.7 +/- 53.7 and 149.4 +/- 13.1 visits in KLH- and KLH-cVIP
      conjugate-immunized turkeys. Turkeys that showed an immune response to KLH-cVIP
      immunization did not exhibit incubation behavior, whereas 54% and 33% of non- and
      KLH-immunized hens incubated their eggs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711178
TI  - Regional differences in bioelectrical properties and anion secretion in cultured
      epithelia from rat and human male excurrent ducts.
AB  - Bioelectrical properties and anion secretion in cultured epithelia from different
      regions of rat and human male excurrent ducts were studied by measuring the short
      circuit currents (ISC). In all regions of the rat excurrent duct, Cl- secretion
      accounts for over 90% of the basal ISC, although the magnitude varied in
      different regions. Cl- secretion was found to be mediated by a Cl-/HCO3-
      exchanger, an Na+/H+ exchanger, and an Na+/K+/2Cl- symport located on the
      basolateral side of the epithelial cells. Forskolin, an activator of adenylate
      cyclase, and ionomycin, a Ca2+ ionophore, were used to investigate the relative
      importance of cAMP and Ca2+ as intracellular messengers regulating Cl- secretion
      in different regions. It was found that in both species, the forskolin-evoked ISC
      response was larger in the proximal end (efferent duct/caput epididymidis
      [rat/human, respectively]) than in the distal end (cauda/corpus epididymidis).
      The response to ionomycin in the rat cauda epididymidis (distal end) was larger
      than that in the efferent duct (proximal end); on the other hand, no significant
      difference in the ionomycin-induced ISC was observed in the caput and the corpus
      regions from the human epididymis. Our results indicate that while the cAMP- and
      Ca(2+)-dependent pathways are both involved in regulating Cl- secretion in all
      regions along the male excurrent ducts in both species, a regional difference
      exists with respect to the relative importance of the two regulatory pathways
      involved in Cl- secretion along the male reproductive tract.

PMID- 7711179
TI  - Identification of a sperm penetration factor in the oviduct of the golden
      hamster.
AB  - Previously, we found oviductal eggs to be significantly more penetrable and
      fertilizable in vitro than ovulated eggs collected from the ovarian bursa, while
      bursal eggs were comparable to mature (unovulated) follicular eggs. Incubation of
      follicular eggs with a soluble eluate of oviductal egg cumulus complexes (COF)
      increased sperm penetration: the activity was macromolecular, was destroyed at 56
      degrees C, and was produced in the oviduct. We now report purification of this
      oviductal factor that enhances penetration of follicular eggs and have identified
      it as oviductin (OVN). Oviducts, 1-1.5 h post-LH from eCG-primed females, were
      homogenized and the cytosolic fraction was chromatographed on a Helix pomatia
      lectin affinity column; specific proteins were eluted with 0.2 M N-acetyl-D
      galactosamine. Fractions were monitored by dot-blot assay using as the primary
      antibody monoclonal antibody (mAb) 1C4 against OVN. Proteins were resolved by one
      dimensional SDS-gel electrophoresis, followed by electrotransfer and
      immunostaining of Western blots. OVN fractions were indexed to COF by
      quantitative dot-blot assay, and activity was bioassayed by penetration of
      follicular eggs within 1 h of coincubation with precapacitated sperm +/- factors:
      COF and BSA (high and low controls, respectively) and fractions from the lectin
      isolated peak. The mean penetration rates for three isolations were 17 +/- 4.0a,
      51.7 +/- 5.0b, and 49 +/- 2.7b% for BSA, COF, and column fractions, respectively
      (p < or = 0.05). Purified OVN bound to follicular zonae during culture. Acrosome
      intact sperm heads bound OVN during 30 min of incubation both before (t = 0 h)
      and after capacitation (t = 5.5 h) (visualized by indirect
      immunofluorescence).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711180
TI  - Expression of an avian protamine in transgenic mice disrupts chromatin structure
      in spermatozoa.
AB  - The objective of this study was to determine the consequences of disrupting
      spermatozoal chromatin condensation on spermatozoal development and function. The
      avian protamine, galline, was targeted to spermatids of transgenic mice using the
      mouse protamine 1 gene promoter. Three transgenic mouse lines were established
      that expressed galline mRNA at 65%, 120%, and 185% of the level found in rooster
      testis. Galline mRNA accumulated in round spermatids to levels similar to that of
      mouse protamine and, as with the mammalian counterpart, translation was delayed
      until the elongating spermatid stage. Protein gels revealed that galline
      accumulated in mature spermatozoa whereas mouse protamines were reduced,
      suggesting that galline competes with protamines for binding to spermatozoal DNA.
      Acridine orange binding analysis indicated that DNA of the transgenic spermatozoa
      was not as tightly packed as that of controls. This was corroborated by electron
      microscopy, which revealed disruption of the normal dense chromatin structure of
      spermatozoal heads. Despite these perturbations of chromatin condensation, the
      transgenic spermatozoa were functionally normal, as the majority of transgenic
      mice had normal fertility. However, in mice that expressed excessive galline,
      there was a gradual destruction of seminiferous tubules leading to infertility.
      Our findings suggest that very precise packaging of DNA in germ cells may not be
      essential for subsequent unpackaging in the pronucleus of fertilized eggs and for
      subsequent normal development of the embryo.

PMID- 7711181
TI  - Effects of chronic low-dose cyclophosphamide exposure on the nuclei of rat
      spermatozoa.
AB  - Previous studies from our laboratory have shown that chronic exposure of the
      father to low doses of cyclophosphamide results in a significant increase in
      early embryonic death with little effect on the male reproductive system in rats.
      Such effects on progeny outcome are hypothesized to be mediated by an action of
      the drug on the nucleus of spermatozoa. The purpose of the present studies was to
      investigate the effects of cyclophosphamide treatment for 1 or 6 wk on the
      pattern of decondensation of sperm nuclei and on the sulfhydryl content of sperm
      nuclear proteins. Adult male rats were treated with cyclophosphamide (6.1
      mg/kg/day) daily for 1 or 6 wk. Cauda epididymal spermatozoa were collected,
      demembranated, and then incubated with dithiothreitol (DTT) and proteinase K. The
      in vitro decondensation pattern of the nuclei of spermatozoa was divided into two
      phases: nuclear swelling and nuclear elongation. Spermatozoa from animals treated
      for 1 wk with cyclophosphamide showed the same decondensation pattern as those
      treated with vehicle (saline) alone. However, spermatozoa from animals treated
      for 6 wk with cyclophosphamide showed normal initial nuclear swelling but had a
      markedly affected nuclear elongation pattern. The changes with time in the
      decondensation pattern of these spermatozoa were quantitated by morphometric
      analysis of the head region of the spermatozoa. The nuclear area, curvature, and
      length of spermatozoa obtained from chronically drug-treated males were all
      significantly smaller than for those obtained from controls, while cell diameter
      was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711182
TI  - Characterization of Fsc1 cDNA for a mouse sperm fibrous sheath component.
AB  - The fibrous sheath is a major cytoskeletal structure in the principal piece of
      the mammalian sperm flagellum. We have cloned a cDNA and used it to characterize
      the expression of mRNA for a mouse sperm fibrous sheath protein. Peptides from a
      tryptic digest of fibrous sheath proteins were separated by HPLC and a 31 amino
      acid sequence was obtained from one of the peptides. Through the use of
      degenerate oligonucleotide polymerase chain reaction (PCR) primers predicted from
      this sequence, an 80-bp product was amplified from mouse testis first-strand
      cDNA. This was utilized as a probe to isolate a 2.9-kb cDNA clone from a mouse
      round spermatid cDNA library. Sequence analysis of the cDNA clone showed that it
      encodes a protein with an open reading frame of 849 amino acids and includes the
      original peptide sequence. The predicted protein has a molecular weight of 93,795
      and contains 32 cysteine residues and 32 potential phosphorylation sites. It has
      no significant homology with other known cytoskeletal proteins. Northern blot
      analysis detected an mRNA of approximately 3 kb that was abundant in round
      spermatids of the mouse and in testes from six other mammalian species, but not
      in twelve somatic tissues from the mouse. In situ hybridization analysis
      indicated that the mRNA is first detected in step 1-6 spermatids, is most
      abundant in step 8-12 spermatids, and decreases in amount in step 13-15
      spermatids, suggesting that expression of the mRNA occurs in the postmeiotic
      phase of spermatogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711183
TI  - Exportation of mouse vas deferens protein, a protein without a signal peptide,
      from mouse vas deferens epithelium: a model of apocrine secretion.
AB  - Mouse vas deferens protein (MVDP) is a major androgen-dependent protein of
      deferential fluid. It is specifically expressed in the epithelium of the mouse
      vas deferens. Its amino acid sequence as deduced from the nucleotidic sequence of
      its cDNA does not possess a signal sequence characteristic of secretory proteins.
      In vitro, transcription of MVDP cDNA followed by translation of mRNA in the
      rabbit reticulocyte system, in the absence or the presence of microsomes,
      demonstrated that there was no internalization of MVDP into microsomes that could
      protect it from degradation by proteinase K; this confirmed the absence of signal
      sequence. Moreover, MVDP has its NH2-terminus blocked. To understand how MVDP can
      be exported, its ultrastructural distribution and secretion process were analyzed
      by means of electron microscopy. Immunolocalization of MVDP revealed that it was
      distributed in the whole cytoplasm; it was never detected in the lumen of
      endoplasmic reticulum, Golgi apparatus, or vesicles but was abundant in apical
      protrusions and in the fluid, where it was associated with cellular material
      undergoing degradation. These data clearly demonstrated that exportation of MVDP
      into the luminal fluid does not occur in the classical manner for secretory
      proteins but rather involves an apocrine secretion process.

PMID- 7711184
TI  - Luteinizing hormone (LH) and corticosterone in proestrous afternoon restore the
      follicle-stimulating hormone secretion at early estrus in adrenalectomized LH
      releasing hormone antagonist-treated rats.
AB  - Administration of the antiprogestagen RU486 in the morning of proestrus abolishes
      the secondary surge of FSH during early estrus in the rat without preventing the
      drop in serum inhibin. In addition, the injection of an ovulatory dose of LH to
      RU486-injected rats does not restore the secondary surge of FSH. Since RU486 is a
      potent antiprogesterone with antiglucocorticoid activity, in the first experiment
      we compared the effects of RU486 and a specific antiprogesterone serum (APS),
      administered on proestrus, on the secretion of FSH during early estrus. While
      RU486 and APS reduced the primary surge of LH and FSH, only RU486 abolished the
      secondary secretion of FSH. In the second experiment, rats injected with LHRH
      antagonist (LHRHa) and ovine LH (oLH) were adrenalectomized (ADX) or sham-ADX in
      the morning and injected with corticosterone (B) or oil in the afternoon of
      proestrus. LHRHa completely eliminated, and oLH restored, the secretion of FSH at
      0200 h in estrus. ADX reduced FSH serum concentration at 0200 h in estrus, and B
      reversed this effect in rats injected with LHRHa and oLH. The results of these
      experiments indicate that, in the rat, the LHRH-independent secretion of FSH
      during early estrus is evoked by the combined effects of the preovulatory surge
      of LH and the rise in serum B on proestrous afternoon.

PMID- 7711185
TI  - Baculovirus-insect cell production of bioactive choriogonadotropin-immunoglobulin
      G heavy-chain fusion proteins in sheep.
AB  - A hybrid cDNA encoding a fusion protein between the beta subunit of hCG (beta
      hCG) and constant domains of a mouse IgG heavy chain (CH1-3) was inserted into a
      baculovirus expression vector. Insect cells transfected with foreign DNA
      synthesized multimeric forms of fusion protein that inhibited hCG-induced steroid
      hormone secretion by mouse Leydig tumor cells. Leydig cells were lysed by beta
      hCG-CH1-3 in the presence of complement. Intravenous injection of beta hCG-CH1-3
      in rams was associated with testicular mononuclear leukocyte infiltration,
      interstitial tissue damage, and a transient depression in circulatory
      testosterone (levels returned to normal within 2 wk). It appears that targeted
      cell-killing can be mediated by recombinant proteins composed of the receptor
      binding moiety of hormones and truncated effector (Fc) regions of lethal
      antibodies.

PMID- 7711186
TI  - Prostaglandin F2 alpha receptors in the early bovine corpus luteum.
AB  - Since the early CL (< or = 4 days after ovulation) does not regress after
      injection of PGF2 alpha, this study was designed to determine whether number or
      affinity of PGF2 alpha receptors was lower in the early as compared with the
      midstage CL. Heifers were randomly assigned to have ovaries removed on Day 2, 4,
      6, or 10 (n = 4 heifers per day; Day 0 = day of ovulation). Plasma progesterone
      concentrations and the weight and size of the CL increased from Day 2 to 6,
      indicating normal CL development. Plasma membranes from individual CL were
      evaluated for PGF2 alpha receptor concentration and affinity by Scatchard
      analysis. CL from each of the 4 days of the estrous cycle were not different with
      respect to PGF2 alpha receptor concentration (number per microgram of plasma
      membrane protein) and affinity. To examine tissue specificity, PGF2 alpha binding
      was evaluated in 12 organs or tissues. High-affinity PGF2 alpha receptors were
      found in the CL and adrenal medulla but not in granulosa cells or other tissues.
      In conclusion, a single class of high-affinity PGF2 alpha receptors was present
      within the bovine CL by 2 days after ovulation; therefore the reported lack of
      responsiveness to PGF2 alpha in the early CL was not attributable to a deficiency
      of high-affinity PGF2 alpha receptors.

PMID- 7711187
TI  - Integrin receptor alpha 6 beta 1 is localized at specific sites of cell-to-cell
      contact in rat seminiferous epithelium.
AB  - With the aim of investigating the presence and role of integrin receptors in cell
      to-cell interactions during spermatogenesis, we have immunolocalized alpha 6A
      integrin chain in the rat seminiferous epithelium. In both prepubertal and adult
      seminiferous epithelium, the antigen was found to be restricted to definite sites
      of intercellular contact, following a stage-specific distribution almost
      invariably identical to that known for beta 1 chain. In the adult seminiferous
      epithelium, positivity for both antigens was found exclusively around the
      profiles of elongating and maturing spermatids and, in most but not all stages,
      at a characteristic suprabasal position. In the prepubertal rat, the antigen is
      localized along a very regular suprabasal line of intercellular contacts. In
      immunoprecipitation experiments on both seminiferous epithelium explants and
      Sertoli cell cultures from 3-wk-old rats, anti-alpha 6A antibody coprecipitates a
      polypeptide of 118 kDa, presumably corresponding to beta 1 chain. These data
      strongly suggest that the integrin heterodimer alpha 6A beta 1 is expressed at
      sites of intercellular contact in the rat seminiferous epithelium. The stage
      specific and restricted pattern observed by immunofluorescence suggests that this
      integrin is involved in regulatory interactions between Sertoli cells and germ
      cells during spermatogenesis.

PMID- 7711188
TI  - Gonadotropin surge-attenuating factor bioactivity in serum from superovulated
      women is not blocked by inhibin antibody.
AB  - Primary pituitary cultures from adult female rats were used to investigate
      gonadotropin surge attenuating factor (GnSAF) bioactivity. Serum from
      superovulated women was charcoal-treated and incubated with either an inhibin
      antibody (MC4), normal sheep serum (NSS), or serum-free defined medium (SFDM)
      before addition to cell culture. The reduction in GnRH-induced LH secretion
      (GnSAF bioactivity) produced by the serum (30.1 +/- 6.5%, p < 0.001, of control)
      was not altered by prior incubation with either MC4 or NSS (24.9 +/- 3.6 and 23.2
      +/- 2.7%, p < 0.001, of control, respectively). This indicates that GnSAF
      bioactivity present in serum from superovulated women is not entirely
      attributable to inhibin. Recombinant human inhibin reduced basal FSH secretion to
      24.6 +/- 4.7% (p < 0.001) of the control value. However, this was totally
      abolished by prior incubation with MC4, but not NSS. We have also shown that
      ovarian steroids are not responsible for GnSAF bioactivity in vitro. In
      conclusion, in contrast to findings in superovulated rats, inhibin antibody did
      not block GnSAF bioactivity in serum from superovulated women.

PMID- 7711189
TI  - Differences in amino acid content of preimplantation mouse embryos that develop
      in vitro versus in vivo: in vitro effects of five amino acids that are abundant
      in oviductal secretions.
AB  - Although it is now well established that amino acids can improve preimplantation
      development of mouse embryos in vitro, the mechanisms by which they influence
      development have not been determined. To investigate these mechanisms, we
      compared the contents of seven abundant amino acids (alanine, aspartate,
      glutamate, glycine, serine, and taurine) in 4-8-cell embryos and blastocysts
      developing in vivo with the contents in those developing from the 2-cell stage in
      vitro. We also studied the effects of five amino acids (alanine, glutamate,
      glutamine, glycine, and taurine) that are abundant in the oviductal lumen on the
      amino acid content of embryos developing in vitro. Blastocysts that developed in
      vitro contained about six times more alanine and about one-sixth as much taurine
      as blastocysts that developed in vivo, but the same amounts of glycine and
      serine. In the presence of glycine and four other abundant amino acids in
      oviductal secretions, however, blastocysts that developed in vitro had higher
      levels of both glycine and serine than those that developed in vivo. In contrast,
      glycine either alone or in combination with the other amino acids reduced the
      alanine content of blastocysts developed in vitro to nearer that of blastocysts
      developing in vivo. Similarly, taurine in the medium allowed blastocysts
      developed in vitro to increase their content of this amino acid to normal levels.
      The levels of taurine and, somewhat surprisingly, glutamine and glycine became
      abnormally low in embryos within 24 h of the onset of in vitro culture in medium
      that did not contain the amino acid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711190
TI  - Interactions between germ cells and Sertoli cells in the testis.
AB  - The "nurse cell" function of Sertoli cells in spermatogenesis was originally
      tacitly assumed on the basis of the anatomical relationships between cells in the
      testis. In mammals, from very early in prenatal development to the onset of
      meiosis and to the ultimate production of spermatozoa, the relationship between
      the germinal cells and the Sertoli cells is important and apparently obligatory.
      The experimental evidence supports the notion that the primary endocrine
      regulation of spermatogenesis via FSH and testosterone is manifested through
      actions on the Sertoli cells. Although diverse strategies are used by Sertoli
      cells to support germ cell development, one of the most important roles of
      Sertoli cells is the regulation of the intratubular and intercellular environment
      adluminal to the tight junctional complexes. The meiotic and post-meiotic germ
      cells are sequestered by Sertoli-Sertoli junctional complexes in an adluminal
      compartment that is isolated from the serum or lymph. As a result of this
      sequestering activity, the secretion products of the Sertoli cells and the
      meiotic germ cells determine the composition of this local environment that can
      influence meiosis as well as spermatid and spermatocyte development. Evidence is
      accumulating that paracrine and autocrine factors from Sertoli and germ cells are
      important in the functioning of both cell types. While it is important to know
      what Sertoli cells and germ cells make, it is equally important to know when they
      make it. Distinct but well-defined groups of germ cells interact with Sertoli
      cells in a cyclic pattern. These recurring groups of germ cells define the cycle
      of the seminiferous epithelium during which sperm are produced in an asynchronous
      fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711191
TI  - Regulation of expression of steroidogenic enzymes in Leydig cells.
AB  - The Leydig cell of the testis is the only cell in the male that has the capacity
      to synthesize testosterone from cholesterol. Testosterone is critical during
      fetal development for male sexual differentiation, and postnatally for initiation
      and maintenance of spermatogenesis and the expression of the male secondary sex
      characteristics. The biosynthesis of testosterone requires the activities of four
      enzymes, cholesterol side-chain cleavage enzyme (P450scc), 3 beta-hydroxysteroid
      dehydrogenase/delta 5-delta 4 isomerase (3 beta HSD), 17 alpha-hydroxylase/C17-20
      lyase (P450(17 alpha)), and 17-ketosteroid reductase. The expression of these
      enzymes appears to be regulated by different mechanisms. The recent isolation of
      the mouse cDNAs and structural genes that encode these enzymes has enabled us to
      begin to investigate the regulation of their expression at the molecular level.
      This review discusses the regulation by cAMP and steroids of three enzymes in
      Leydig cells, P450scc, P450(17 alpha), and 3 beta HSD, as well as
      characterization of the promoters of the mouse genes that encode P450scc and
      P450(17 alpha).

PMID- 7711192
TI  - Regulation of epididymal epithelial cell functions.
AB  - It is well established that the epididymis is the site where spermatozoa are
      matured and stored, but our understanding of the regulation of epididymal
      epithelium functions and their effects on spermatozoa is still fairly limited.
      The most active regulator of epididymal functions seems to be
      dihydrotestosterone, the 5 alpha-reduced metabolite of testosterone. Our
      laboratory has focused on the regulation of 5 alpha-reductase, with studies
      encompassing its messenger RNA, protein and enzyme activity. We have also
      investigated the hormonal regulation and distribution of other specific key
      proteins found in epididymal epithelial cells that play critical roles in the
      function of these cells. These proteins include clusterin or sulfated
      glycoprotein-2 and the glutathione S-transferases (GST). Using complementary
      experimental approaches, including orchidectomy and hormonal replacement,
      efferent duct ligation, and developmental studies, we have established that 5
      alpha-reductase enzyme activity is present in both nuclear and microsomal
      fractions; the nuclear enzyme appears almost exclusively in the initial segment
      of the epididymis. In addition, 5 alpha-reductase activity and the mRNAs for both
      the type 1 and type 2 form of the enzyme are regulated differentially with
      respect to age and site within the epididymis. Immunolocalization of the protein
      has revealed that it is located in principal cells and that its subcellular
      location is dependent on the region of the epididymis. These results indicate
      that there is both transcriptional and post-transcriptional regulation of the
      expression of 5 alpha-reductase. Clusterin is a hydrophobic protein secreted by
      Sertoli cells and found in high concentration in the epididymis. This
      glycoprotein is expressed at its highest levels in the initial segment and caput
      epididymidis and at very low levels in the corpus and cauda epididymidis of the
      intact rat, and it exhibits a novel pattern of androgen regulation. In the areas
      of highest expression, there is no androgen dependence; however, orchidectomy
      causes a dramatic increase in the message for clusterin, which is suppressible by
      androgens in the segments where expression is normally lowest. The GSTs are a
      family of enzymes thought to play a key role in detoxification. Members of the
      GST family are expressed in a region-dependent manner along the rat epididymis.
      We have found that the localization of one member of this enzyme family, GST P,
      or subunit Yp, is selective for basal cells in the corpus and cauda
      epididymidis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7711193
TI  - Microdialysis: a novel tool for research in the reproductive system.
AB  - The technique of microdialysis has been applied extensively in neurobiological
      research. However, its potential as a tool for research in tissues other than the
      brain has not been fully explored. This article describes some of the situations
      in which microdialysis has been employed for studies in reproductive physiology
      and behavior. The examples have been chosen to give the reader a sense of the
      potential of the technique, its strengths, and some of its limitations.

PMID- 7711194
TI  - Implementing transgenic and embryonic stem cell technology to study gene
      expression, cell-cell interactions and gene function.
AB  - This review highlights the use of transgenic mice and gene targeting in the study
      of reproduction, pituitary gene expression, and cell lineage. Since 1980 numerous
      applications of transgenic animal technology have been reported. Altered
      phenotypes resulting from transgene expression demonstrated that introduced genes
      can exert profound effects on animal physiology. Transgenic mice have been
      important for the study of hormonal and developmental control of gene expression
      because gene expression in whole animals often requires more DNA sequence
      information than is necessary for expression in cell cultures. This point is
      illustrated by studies of pituitary glycoprotein hormone alpha- and beta-subunit
      gene expression (Kendall et al., Mol Endocrinol 1994; in press [1]. Transgenic
      mice have also been invaluable for producing animal models of cancer and other
      diseases and testing the efficacy of gene therapy. In addition, cell-cell
      interactions and cell lineage relationships have been explored by cell-specific
      expression of toxin genes in transgenic mice. Recent studies suggest that
      attenuated and inducible toxins hold promise for future transgene ablation
      experiments. Since 1987, embryonic stem (ES) cell technology has been used to
      create numerous mouse strains with targeted gene alterations, contributing
      enormously to our understanding of the functional importance of individual genes.
      For example, the unexpected development of gonadal tumors in mice with a targeted
      disruption of the inhibin gene revealed a potential role for inhibin as a tumor
      suppressor (Matzuk et al., Nature 1992:360: 313-319 [2]. The transgenic and ES
      cell technologies will undoubtedly continue to expand our understanding and
      challenge our paradigms in reproductive biology.

PMID- 7711195
TI  - 1994 Carl G. Hartman Award. Irving Rothchild.

PMID- 7711196
TI  - SSR Research Award. William W. Thatcher.

PMID- 7711197
TI  - SSR Distinguished Service Award. Shelden J. Segal.

PMID- 7711198
TI  - Ascorbic acid and fertility.
AB  - Ascorbic acid has long been associated with fertility, but no consistent study of
      its mechanism of action in reproductive tissues has been made. This article
      considers how three of ascorbic acid's principal functions, namely its promotion
      of collagen synthesis, its role in hormone production, and its ability to protect
      cells from free radicals, may explain its reproductive actions. Data relating to
      both ovary and testis are reviewed since ascorbate accumulates in both tissues.
      Both gonads exhibit cycles of tissue remodeling and of peptide and steroid
      secretion that can be assumed to be ascorbate-dependent. Ascorbic acid may also
      prevent gametes from damage by free radicals during production and fertilization.
      Preliminary data on the concentrations of ascorbic acid in serum and follicular
      fluid from women undergoing in vitro fertilization are presented. They suggest
      that the supply of ascorbic acid to the ovary might be a limiting factor in the
      ability of the preovulatory follicle to grow in response to gonadotropin
      stimulation. It is concluded that  ascorbic acid is a key compound in gonadal
      physiology on which further research is needed and that a reappraisal of its
      potential clinical value in the treatment of various types of male and female
      infertility would be timely.

PMID- 7711199
TI  - Effects of 17 beta-estradiol on distribution of pituitary isoforms of luteinizing
      hormone and follicle-stimulating hormone during the follicular phase of the
      bovine estrous cycle.
AB  - The objective of this study was to examine the influence of 17 beta-estradiol
      (E2) on distribution of LH and FSH isoforms during the follicular phase of the
      bovine estrous cycle prior to the preovulatory surges of LH and FSH. On Day 16 of
      the estrous cycle (Day 0 = estrus), intact controls (CONT; n = 4) were treated
      with prostaglandin F2 alpha (PGF2 alpha) to induce luteal regression and
      initiation of the follicular phase. Other cows were also treated with PGF2 alpha
      and either ovariectomized (OVX; n = 5) or ovariectomized and given E2 implants
      (OVXE; n = 6) to mimic the pattern of increasing E2 concentrations during the
      follicular phase of the estrous cycle. Pituitaries were collected 40 h after
      treatment with PGF 2 alpha or ovariectomy (0 h). Aliquots of pituitary extracts
      were chromatofocused on pH 10.5-4.0 gradients. The LH resolved into thirteen
      isoforms (designated A-L and S, beginning with the most basic form) while FSH
      resolved into nine isoforms (designated I-IX, beginning with the most basic
      form). The percentage of LH as isoform F (elution pH = 9.32 +/- 0.01) was greater
      (p < 0.05) in the OVX group (48.5%) than in the OVXE group (45.0%). LH isoforms I
      (elution pH = 6.98 +/- 0.01) and J (elution pH = 6.48 +/- 0.01) were more
      abundant (p < 0.05) in cows from the OVXE (2.3 and 5.8%, respectively) than the
      OVX group (1.4 and 3.7%, respectively). Distribution of LH isoforms in cows from
      the three groups did not differ (p > 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711200
TI  - Internucleosomal DNA fragmentation in ovine luteal tissue associated with
      luteolysis: in vivo and in vitro analyses.
AB  - Internucleosomal DNA fragmentation, a characteristic of apoptosis, can be
      visualized with agarose gel electrophoresis as discrete low-molecular-weight DNA
      fragments (laddering), in multiples of approximately 185 bp. CL were collected
      from superovulated ewes (control) or at 12 h after injection of prostaglandin F2
      alpha (PGF2 alpha) on various days after hCG injection. The ability of PGF2 alpha
      on Days 8, 10, 12, and 14 (n > or = 3 per day per treatment) to induce luteal
      cell DNA fragmentation was evaluated. DNA was isolated and visualized on agarose
      gels. No DNA fragmentation was observed in CL from control ewes on Days 8, 10, or
      12. Internucleosomal fragmentation of DNA (indicative of apoptosis) as well as
      nonspecific DNA fragmentation (indicative of non-apoptotic cell death) in CL from
      Day 14 controls was observed in two of four animals. Additionally, this pattern
      of DNA fragmentation was observed in CL from ewes treated with PGF2 alpha on all
      days. Evidence of DNA fragmentation was observed in luteal tissue after
      dissociation, yet no fragmentation was observed in unsliced, non-dissociated CL
      collected from Day 10 control ewes (incubated 4 h), or in sliced, non-incubated
      CL. Slicing and incubation alone were sufficient to initiate DNA fragmentation. A
      variety of approaches were utilized to inhibit DNA fragmentation. Only the
      addition of zinc acetate (1 mM) in the incubation medium throughout the 4-h
      incubation period prevented DNA fragmentation that was initiated by slicing (p <
      0.05). There appear therefore, to be one or more intraluteal factors that
      directly initiate DNA fragmentation associated with cell death in
      luteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711201
TI  - Follicle-stimulating hormone, human chorionic gonadotropin, and prolactin
      receptors in hamster corpora lutea or dispersed luteal cells during pregnancy.
AB  - In vitro progesterone (P4) production by hamster luteal cells is stimulated
      throughout pregnancy by FSH and LH. Prolactin (PRL) by itself, however, increases
      P4 synthesis only on Day 12; on Day 4, FSH+LH+PRL induces optimal P4 secretion
      [Biol Reprod 1994; 51:43-49]. In light of these findings, in this study we
      investigated FSH, hCG, and PRL receptors in hamster CL or dispersed luteal cells
      on Days 4, 8, and 12 of pregnancy. Scatchard analysis of hamster CL on Days 4 and
      8 showed considerably more unoccupied hCG receptors than FSH receptors: on Day 4,
      there was 9.5 fmol/mg protein for FSH binding sites vs. 1741 fmol/mg protein for
      hCG binding. Moreover, the binding affinity of hCG was greater than for FSH: the
      Day 4 Kd was 0.136 nM for hCG vs. 0.308 for FSH. Similar differences were
      observed on Day 8. Dispersed luteal cells (large+small cells) were incubated for
      24 h with or without 10 ng of ovine FSH, LH, and PRL or human recombinant FSH (r
      hFSH), alone or in different combinations. The cells were then washed and
      incubated for 4 h with iodinated hCG, FSH, or PRL with or without 100-fold excess
      of unlabeled hormones. The number of binding sites per 200,000 luteal cells did
      not change appreciably for FSH and hCG on Days 4 and 12 of pregnancy, whereas PRL
      binding sites significantly increased on Day 12.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711202
TI  - Basement membrane gene expression by Sertoli and peritubular myoid cells in vitro
      in the rat.
AB  - Both Sertoli and myoid cells have been shown to be required for the appropriate
      deposition of basement membrane in the testis. We sought to define the pattern of
      basement membrane gene expression in Sertoli and peritubular myoid cells in vitro
      in order to begin to understand the regulatory mechanisms involved in basement
      membrane synthesis. Sertoli and myoid cells cultured alone or together were
      examined for synthesis of basement membrane components. Immunocytochemical
      localization demonstrated that Sertoli cells alone produced laminin and collagen
      IV, but not fibronectin, while myoid cells produced all three proteins. In
      Sertoli:myoid cocultures, a sequential deposition of the components into
      extracellular fibers was noted during 5 days of culture. Northern blot analysis
      revealed that mRNA levels for the laminin B1 chain and collagen IV increased from
      Days 3 to 5 in Sertoli cell monocultures. By contrast, the levels of laminin B1,
      collagen IV, heparan sulfate proteoglycan, and fibronectin decreased in the
      cocultures. Transcripts for the laminin A chain were not detected in the myoid
      cells; instead these cells produced the mRNA for the laminin homologue, merosin.
      This observation was confirmed by immunolocalization of merosin to the tunica
      propria of the testis and in cultured myoid cells. These data describe the
      expression of the basement membrane genes by Sertoli and peritubular myoid cells
      and provide the basis for future studies to determine the mechanisms that
      regulate the expression of the basement membrane genes in the testis.

PMID- 7711203
TI  - Rat testin is a newly identified component of the junctional complexes in various
      tissues whose mRNA is predominantly expressed in the testis and ovary.
AB  - Testin I and testin II are the two molecular variants of testin that are
      synthesized and secreted by Sertoli cells in vitro. N-Terminal and partial
      internal amino acid sequence analysis of testin I and testin II reveals that
      these molecules are identical with the exception that testin II has three extra N
      terminal amino acids of TAP compared to testin I. Studies using
      immunohistochemistry suggested that testin is a component of the specialized
      junctional complexes in the seminiferous epithelium and other tissues.
      Immunoreactive testin is localized not only at Sertoli-Sertoli and Sertoli-germ
      cell junctions, but also at sites of similar junctions in the liver, epididymis,
      kidney, and intestine. Other physiological studies have shown that the secretion
      of testin is tightly coupled to the presence of germ cells. In view of its
      possible role in germ cell development and its unique localization in the cell
      junction, the purpose of the present study was to determine the structure of
      testin by sequencing its full-length cDNA. Two synthetic degenerate
      oligonucleotides based on the N-terminal and an internal amino acid sequence were
      used for polymerase chain reaction (PCR) to obtain a 289-bp cDNA fragment. This
      PCR product was subsequently used to isolate a 1371-bp cDNA from a cDNA
      expression library constructed from Sertoli cell poly(A) RNA. This cDNA coded for
      a 333 amino acid peptide that starts with an ATG initiation codon from the 5' end
      and ends with a TGA termination codon located 245 nucleotides before the
      polyadenylation site. The deduced amino acid sequence indicates that testin
      contains a 16 amino acid signal peptide with two possible cleavage sites that
      yield 314 and 317 amino acids for testin I and testin II with calculated
      molecular weights of 36,029 and 36,299, respectively. Comparison of the entire
      coding region of testin with existing sequences at Genbank, EMBL, and Protein
      Identification Resource indicates that testin shares 58%, 57.4%, and 61% identity
      with rat, mouse, and human cathepsin L at the amino acid level, respectively. The
      positions of all of the 7 Cys residues and 8 of the 10 Trp residues in testin are
      conserved with respect to those present in cathepsin L. It is noted that Cys-122
      in the predicted active site of cathepsin L was replaced with Ser-122 in testin.
      In view of the striking primary sequence homology between testin and cathepsin L,
      we assayed the proteolytic activity of testin using conditions known to activate
      cathepsin L.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7711204
TI  - Retinol processing by the peritubular cell from rat testis.
AB  - The cells that surround and support the seminiferous epithelium of the tubules in
      the testis, i.e., the peritubular or myoid cells, are known to contain relatively
      high amounts of cellular retinol-binding protein (CRBP). This suggests that they
      may play an important role in the movement or metabolism of retinol (vitamin A
      alcohol), which is required for the maintenance of spermatogenesis. Peritubular
      cells in culture, isolated from the testes of the 20-day-old rat, maintained high
      levels of CRBP and had the ability to internalize retinol from retinol-binding
      protein (RBP), the blood transport protein for retinol, in a manner suggesting a
      receptor-mediated process. Little of the internalized retinol was esterified, in
      contrast to what occurs in other cell types that contain high amounts of CRBPs,
      and very little, if any, lecithin-retinol acyltransferase activity was present in
      microsomes obtained from the cultured cells. The cells did, however, have the
      ability to synthesize and release their own RBP to the medium. This suggests that
      retinol from the blood may actually reach the seminiferous epithelium by passing
      across the peritubular cell, released on a new molecule of RBP, rather than by
      entering into the tubule bound to the preexisting RBP present in the interstitial
      fluid.

PMID- 7711205
TI  - Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide-induced
      ovarian follicular depletion in rhesus monkeys.
AB  - Several investigators have demonstrated that LHRH agonists (LHRHa) inhibit
      ovarian follicular depletion induced by chemotherapeutic agents in rodents. It is
      not clear whether or not the same effects occur in primates. Six adult female
      rhesus monkeys underwent unilateral ovariectomy and were divided into two groups
      that received monthly injections of either Lupron depot (LHRHa) or placebo
      vehicle. Both groups received cyclophosphamide (CTX) injections. Weekly blood
      samples were assayed for FSH, estradiol and progesterone. Mean serum FSH levels
      significantly increased in the CTX group and significantly decreased in the
      LHRHa+CTX group. At the end of treatment, the remaining ovary was removed and
      serially sectioned, and ovarian follicle number and size were analyzed. CTX
      resulted in a significant reduction of nonprimordial follicles < 50 microns in
      diameter. The rate of loss of primordial follicles was expressed as a percentage
      of the original follicle count. During the treatment period, 64.6 +/- 2.8% of the
      total primordial follicles were lost in the CTX group compared to only 28.9 +/-
      9.1% in the LHRHa+CTX group (p < 0.05). The percentage rate of decline per day
      was 0.120 +/- 0.012 for the CTX group compared to 0.057 +/- 0.019 (p < 0.05) for
      the LHRHa+CTX group. The findings indicate that LHRHa can protect the ovary
      against CTX-induced damage in rhesus monkeys.

PMID- 7711206
TI  - Gonadotroph responsiveness in orchidectomized sheep: IV. Effect of estradiol
      infusion during the breeding and anestrous seasons.
AB  - The interaction between estradiol (E2) and season on gonadotroph function was
      assessed in orchidectomized sheep (wethers). Wethers in the breeding (November)
      or anestrous (May) season received E2 (in 20% ethanol-saline [vehicle]) by
      continuous infusion at rates of 0.31, 1.25, 5, or 20 micrograms/h (n = 6
      wethers/group). Controls received vehicle alone. Gonadotroph responsiveness (LH
      release induced by 500 ng GnRH, i.v.) was assessed at the end of the 48-h
      infusion period. Mean serum concentrations of E2 at the end of infusion were <
      0.6 pg/ml in animals receiving vehicle, and 2.5 +/- 0.3, 10.7 +/- 0.4, 35.1 +/-
      0.9, and 86.1 +/- 4.1 pg/ml in animals receiving 0.31, 1.25, 5, and 20 micrograms
      E2/h, respectively. Mean serum concentrations of LH and FSH, the amplitude and
      frequency of LH secretion, and gonadotroph responsiveness did not differ (p >
      0.05) with season in controls. Infusion of E2 at 5 or 20 micrograms/h decreased
      (p < 0.05) serum concentrations of LH and FSH and eliminated episodic secretion
      of LH, regardless of season. Conversely, E2 infusion at 0.31 microgram/h resulted
      in significant suppression of gonadotropin secretion in May, but not November.
      Similarly, the reduction in serum concentrations of LH and FSH induced by E2
      infusion at 1.25 micrograms/h was more pronounced (p < 0.05) in May than
      November. Compared to gonadotroph responsiveness in controls, responsiveness in
      the breeding, but not the anestrous, season increased (p < 0.05) after infusion
      of 0.31 microgram E2/h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711207
TI  - Effect of accessory sex gland fluid from bulls of differing fertilities on the
      ability of cauda epididymal sperm to penetrate zona-free bovine oocytes.
AB  - The ability of accessory sex gland fluid to affect the fertility of cauda
      epididymal sperm was evaluated for 10 bulls that ranged in fertility from 6.2%
      below to 6.0% above the average fertility of bulls at artificial breeding
      cooperatives. Cauda epididymal sperm collected from indwelling vasa deferentia
      catheters and cauda epididymal sperm exposed to accessory sex gland fluid from
      the same bull were compared on the basis of their rates of in vitro penetration
      of zona-free oocytes after heterospermic insemination. Incubation of cauda
      epididymal sperm with accessory sex gland fluid significantly enhanced the
      ability to penetrate oocytes, and bull fertility affected the magnitude of this
      improvement. For bulls of average and higher fertility, the positive influence of
      accessory sex gland fluid on penetrating ability of sperm was highly significant
      (p < 0.0001). Accessory sex gland fluid from bulls of below-average fertility
      also improved the penetrating ability of cauda epididymal sperm, although not
      significantly (p = 0.07). Heterospermic competitions compared the penetrating
      ability of cauda epididymal sperm exposed to homologous accessory sex gland fluid
      with a portion of the same sperm population incubated in heterologous accessory
      sex gland fluid from a bull of contrasting fertility. In experiments involving
      sperm from 12 different bulls, paired in 42 fertile/subfertile combinations,
      samples of cauda epididymal sperm mixed with accessory sex gland fluid from the
      higher-fertility bulls had greater oocyte-penetrating ability than when aliquots
      of that sample were mixed with accessory gland fluid from lower-fertility bulls
      (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711208
TI  - Hypothalamic changes in norepinephrine release in rats with estradiol valerate
      induced polycystic ovaries.
AB  - Chronic anovulation and polycystic ovaries (PCO) can be induced by a single i.m.
      injection of estradiol valerate (EV, 2 mg in oil) in the rat. Constant exposure
      to high plasma levels of estradiol provokes a neurotoxic effect on the
      hypothalamic neurons, including those from the arcuate nucleus. Because of the
      important participation of hypothalamic norepinephrine (NE) in the regulation of
      GnRH release and the possible noxious effect of prolonged exposure of these
      neurons to estradiol, our interest was to study the activity of the noradrenergic
      neurons innervating the hypothalamus. We analyzed the biosynthesis, content, and
      release of NE from the noradrenergic nerve terminals of the hypothalamus during
      the PCO condition. We found a decrease in tyrosine hydroxylase (TH) activity and
      in the content of dopamine (DA) in the anterior hypothalamus after 2 mo of EV
      injection, whereas dopamine-beta-hydroxylase (D beta H) was increased without
      changes in NE content. No variations in TH activity or in DA and NE contents in
      the medial hypothalamus were observed, but a decrease in D beta H activity was
      evident. After 2 mo of EV administration, an increase in the electrically induced
      release of NE from anterior hypothalamic blocks incubated in vitro was detected;
      this effect was not evidenced in the medial hypothalamus. After 5 mo of EV
      administration, release of NE increased in anterior hypothalamic blocks but
      decreased in medial hypothalamic tissue. The inhibitory effect of morphine on NE
      release found in control animals was increased in the hypothalamus from PCO rats,
      suggesting an increased number of mu-opioid binding sites in noradrenergic
      neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711209
TI  - Expression of P450 17 alpha-hydroxylase and P450aromatase genes in isolated
      granulosa, theca interna, and theca externa layers of chicken ovarian follicles
      during follicular growth.
AB  - Concentrations of estradiol (E), testosterone (T), and progesterone (P) and
      levels of the 1.9-kb and 4.0-kb mRNA encoding P450 17 alpha-hydroxylase (P450 17
      alpha) and P450aromatase (P450arom), respectively, were measured in the isolated
      granulosa, theca interna, and theca externa of the largest preovulatory (F1-F4)
      follicles of the chicken 20 h and 3 h before expected ovulation of F1. In the
      granulosa layer, E and T concentrations remained low throughout this period of
      follicular growth, whereas P concentrations were high 3 h before ovulation in F2
      and F1 follicles. E levels were highest in the theca interna and externa of the
      smallest (F4) follicle, decreasing progressively with follicular growth. T
      content of theca interna and granulosa was greater in less mature F4-F2 follicles
      than in the most mature (F1) follicle, whereas theca externa contained little T.
      P was quantifiable in significant amounts only in granulosa tissue, peaking in F2
      and F1 follicles at 3 h before ovulation, at which time plasma levels of steroids
      also rose significantly. P450 17 alpha was expressed mainly in theca interna,
      whereas the P450arom mRNA levels found in theca externa reflected the pattern of
      E in this compartment. Expression of these two genes was very low in granulosa
      tissue, remaining unchanged during follicular growth. These results indicate that
      E and T synthesis in the chicken ovary is regulated, at least in part, at mRNA
      levels of P450 17 alpha and P450arom in the theca interna and theca externa
      layers during follicular growth.

PMID- 7711210
TI  - Follicular stage-dependent regulation of rat granulosa cell plasminogen activator
      system by transforming growth factor-alpha in vitro.
AB  - In the present study, we have examined the influence of transforming growth
      factor-alpha (TGF alpha) and FSH in vitro on the granulosa cell plasminogen
      activator (PA) system accompanying cell proliferation and differentiation during
      follicular development. Undifferentiated and differentiated rat granulosa cells
      from diethylstilbestrol (DES)- and eCG-treated immature rats, respectively, were
      cultured in medium containing FSH (400 ng/ml), TGF alpha (0.5-50 ng/ml), and/or
      transforming growth factor-beta (TGF beta; 25-100 ng/ml). Net secreted PA (PAs)
      and cell-associated PA (PAc) activities were higher in differentiated cells and
      were stimulated by TGF alpha (but not by TGF beta) in a concentration-dependent
      manner. Basal and FSH-stimulated PAs was higher than PAc and accounted for 70-80%
      of the total PA activity in both cell preparations. FSH-stimulated PA activities
      increased in undifferentiated granulosa cells but decreased in differentiated
      cells with increased duration of culture. A biphasic effect (stimulatory in the
      first 24 h and inhibitory thereafter) of TGF alpha on FSH-induced PA activities
      was observed in the cultures of undifferentiated granulosa cells. Whereas both
      urokinase (uPA) and tissue (tPA) PA appeared to be present in cultures of
      granulosa cells from DES-treated rats, only tPA could be detected in those from
      eCG-treated animals. TGF alpha increased basal tPA activity at both stages of
      follicular development but inhibited activities of uPA in undifferentiated
      granulosa cells, irrespective of the presence of FSH. This growth factor
      stimulated basal progesterone (P) and 20 alpha-dihydroprogesterone (20 alpha-OH
      P) secretion (an index of granulosa cell differentiation), the effect being more
      pronounced at the late stage of follicular development.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7711211
TI  - Norethisterone metabolites modulate the uteroglobin and progesterone receptor
      gene expression in prepubertal rabbits.
AB  - Norethisterone (NET) is a synthetic progestin, used as a contraceptive agent,
      that is biotransformed at target tissues into 5 alpha-NET and 3 beta,5 alpha-NET,
      which possess different pharmacological properties. The effects of these
      metabolites on the expression of uteroglobin (UG) and progesterone receptor (PR)
      genes, both regulated by progesterone (P4), were evaluated in the uterus of
      prepubertal female rabbits that were simultaneously treated with P4 (1.0 mg) for
      5 consecutive days. As determined by Western and Northern blot analyses, 5 alpha
      NET inhibited the P4-induced UG gene expression in a dose-dependent manner. A
      similar inhibition was observed with the administration of RU-486. The estrogenic
      agent 3 beta,5 alpha-NET and estradiol at a dose of 1.0 mg also inhibited the UG
      gene expression induced by P4. Both 5 alpha-NET and 3 beta,5 alpha-NET blocked
      the PR down-regulation induced by P4 as assessed by Western and Northern blot
      methods. The inhibition of UG synthesis and PR down-regulation by 5 alpha-NET and
      3 beta,5 alpha-NET indicates that these NET metabolites possess
      antiprogestational properties.

PMID- 7711212
TI  - Expression of quinone reductase activity in embryonal and adult porcine tissues.
AB  - Quinone reductase (QR; EC 1.6.99.2) is recognized as a major
      antimutagenic/anticarcinogenic enzyme in the organism. Our recent studies
      demonstrated the presence of significant QR activity in the early human placenta;
      whether this enzyme is expressed by the mammalian embryo is not known at present.
      In the investigation reported here, we sought to determine whether or not QR
      activity is detected in porcine embryonal tissues and if so, how early this
      expression takes place. In addition, the enzyme activity in the embryo was
      compared to that present in adult porcine tissue. Enzyme activity was determined
      by a colorimetric method with menadione as substrate in the presence of
      tetrazolium salt (MTT). NADH was a preferable cofactor in the embryo, whereas in
      the adult tissues NADPH was a better cofactor. Results show that the enzyme is
      present in all the embryonal organs tested from a very early age (30 days of
      gestation). Among the organs tested, activity was highest in the porcine embryo
      liver, and the specific activity remained unchanged until Day 70. Activity in the
      embryonal kidney increased with advancing gestation. The enzyme activity in
      embryonal tissues was much lower than that measured in the adult liver (30-40
      fold). These findings suggest that the embryo has the potential for inactivating
      carcinogens/mutagens that will subsequently be eliminated by the maternal
      organism, thus protecting against adverse environmental impacts during the most
      critical period of development.

PMID- 7711213
TI  - Ontogeny of reproductive abnormalities induced by deregulation of anti-mullerian
      hormone expression in transgenic mice.
AB  - Anti-mullerian hormone, normally responsible for the regression of mullerian
      ducts in male fetuses, induces stunting, germ cell loss, and seminiferous tubule
      formation in ovaries of bovine freemartin fetuses and of transgenic mice, which
      express the human anti mullerian hormone gene under the control of the
      metallothionein promoter. Because the latter have been studied only after birth,
      we undertook a detailed chronological study of their reproductive organs.
      Mullerian ducts of transgenic female fetuses regressed at the same time as those
      of normal or transgenic males. Maximal reduction of germ cell number occurred
      between 16 days postcoitus and birth, when most transgenic oocytes were still in
      the leptotene stage of the meiotic prophase, whereas normal oocytes had already
      reached the pachytene phase. Interference with progression of the meiotic
      prophase and germ cell loss in the fetal ovary are probably responsible for
      subsequent ovarian regression and retardation of follicle growth. Seminiferous
      tubule formation was not detectable prior to birth and occurred only rarely in
      postnatal ovaries. Aromatase activity of fetal transgenic ovaries was decreased,
      as well as serum concentration of testosterone in adult transgenic males,
      suggesting that high levels of anti-mullerian hormone may impair Leydig cell
      steroidogenesis.

PMID- 7711214
TI  - Melengestrol acetate at greater doses than typically used for estrous synchrony
      in bovine females does not mimic endogenous progesterone in regulation of
      secretion of luteinizing hormone and 17 beta-estradiol.
AB  - Our working hypothesis was that doses of melengestrol acetate (MGA) greater than
      those typically administered in estrous synchrony regimens would regulate
      secretion of LH and 17 beta-estradiol (E2) as endogenous progesterone (P4) does
      during the midluteal phase of the estrous cycle. We also hypothesized that
      endogenous P4 from the CL would interact with MGA to further decrease the
      frequency of LH pulses and E2. Cows on Day 5 of their estrous cycle (Day 0 =
      estrus) were randomly assigned to an untreated control group (CONT, n = 5) or to
      one of six MGA treatment groups (n = 5 per group): 1) MGA administered orally
      each day via a gelatin capsule at a dose of 0.5 mg MGA/cow with the CL present
      (0.5CIL); 2) 0.5 mg MGA/cow daily in the absence of CL (0.5NO); 3) 1.0 mg MGA
      with CL present (1.0CL); 4) 1.0 mg MGA without CL (1.0NO); 5) 1.5 mg MGA with CL
      present (1.5CL); 6) 1.5 mg without CL (1.5NO). MGA was administered for 10 days
      (Day 5 = initiation of treatment). To regress CL, cows assigned to groups without
      CL received injections of prostaglandin F 2 alpha (PGF 2 alpha; 25 mg) on Days 6
      and 7 of their estrous cycle. All cows were administered PGF2 alpha at the end of
      the 10-day treatment period. During the treatment period, daily blood samples
      were collected to determine concentrations of E2. Serial blood samples were
      collected at 15-min intervals for 24 h on Days 8, 11, and 14 to determine pattern
      of LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711215
TI  - Dosage of the synthetic progestin, norgestomet, influences luteinizing hormone
      pulse frequency and endogenous secretion of 17 beta-estradiol in heifers.
AB  - The objective of this study was to determine whether there were doses at which
      the synthetic progestin, norgestomet, could mimic midluteal phase concentrations
      of progesterone in regulating the secretion of LH and 17 beta-estradiol in bovine
      females. Heifers were randomly assigned to one of five groups to receive: 1) one
      (1Norg, n = 5), 2) two (2Norg, n = 5), 3) four (4Norg, n = 5), or 4) eight
      (8Norg, n = 5) norgestomet implants or to serve as untreated control heifers
      (control, n = 5). On Day 7 (Day 0 = behavioral estrus), implants containing
      norgestomet were inserted, and they remained in place for 10 days. All heifers
      implanted with norgestomet were treated with 25 mg prostaglandin F2 alpha (PGF2
      alpha) on Days 7 and 8 to lyse the CL. Controls were treated with 25 mg PGF2
      alpha at the time norgestomet implants were removed from heifers of the other
      treatment groups. Blood samples were collected every 15 min for 24 h on Days 10
      and 16 to determine the frequency of LH pulses. Beginning 24 h after removal of
      implants, samples of blood were collected at 4-h intervals for 96 h to determine
      the time of the preovulatory surge of LH. Daily blood samples were collected from
      Day 2 to Day 48 to determine concentrations of progesterone, and samples
      collected between Days 2 and 17 were used to determine concentrations of 17 beta
      estradiol. Ultrasonography was performed daily from Day 2 until Day 23 to
      evaluate ovarian follicular development.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711216
TI  - Zona pellucida escape by hamster blastocysts in vitro is delayed and
      morphologically different compared with zona escape in vivo.
AB  - The timing and mode of hamster blastocyst escape from the zona pellucida in vitro
      ("hatching") and in vivo were compared on the basis of dynamic and static images
      captured on videotape and computer, respectively. In vivo, most embryos (> or =
      80%) escaped between 0030 h and 0600 h on Day 4 of pregnancy. The zona gradually
      thinned globally and greatly increased in diameter, eventually disappearing.
      Attachment of blastocysts to the uterine epithelium followed within 4 h. Retarded
      embryos also showed global zona lysis. In contrast, zona escape in vitro was
      delayed > or = 29 h both in blastocysts cultured from 1-cell embryos and in
      blastocysts flushed from uteri of mated, naturally cycling hamsters at 2330 h on
      Day 3. Zonae were focally lysed; then blastocysts egressed through the hole,
      leaving most of the zona intact. Global zona lysis never occurred, and retarded
      embryos did not escape. In conclusion, the striking morphological and temporal
      differences in zona escape indicate that the hatching behavior routinely observed
      in cultured hamster blastocysts is not representative of normal events, and
      implicate a uterine contribution to normal zona escape that is lacking in
      culture.

PMID- 7711217
TI  - [Responsibility of the primary care physician in the rational use of
      medications].

PMID- 7711218
TI  - [Future perspectives of primary health care].

PMID- 7711219
TI  - [Fissure sealants versus fluorine varnish on the first permanent molars: economic
      assessment].
AB  - OBJECTIVE: To study school-children between the ages of 6 and 8 in order to make
      an economic comparison between two programmes aimed at preventing caries in the
      first permanent molars: sealants or fluorine varnish. DESIGN: A field trial over
      24 months, with three groups of school-children (sealant/varnish/control).
      SETTING: Primary Care in the school environment (Granada). PATIENTS: 362 school
      children between 6 and 8: 314 were followed for 24 months (100 sealant, 98
      varnish and 116 control group). INTERVENTION: Sealant and fluorine varnish on the
      first healthy permanent molars, with weekly reapplications, using portable
      equipment. MEASUREMENTS AND MAIN RESULTS: The increase was measured over a 24
      month period in both the DMFT (the total of the first permanent molars either
      with caries, missing because of caries or sedice filled) and the DMFS (DMFT, but
      referring to the surface) indexes. In relation to the DMFT, the effectiveness of
      the sealant (difference in increase of DMFT between the sealed and control
      groups) was -1.06 (Standard Error = 0.16) and of the varnish, -0.58 (SE = 0.18),
      which were statistically different figures. For DMFS, the effectiveness of the
      sealant was -1.83 (SE = 0.28) and of the varnish, 1.10 (SE = 0.33), also
      different. The costs per school-child did not differ sealant: 4,524 pesetas (SD =
      1,248), and varnish: 4,373 (SD = 1,267). The cost/effectiveness ratio favored the
      sealant (4,268 pesetas per molar saved against 7,540). CONCLUSIONS: The sealant
      is more efficient (twice that of the varnish). The cost of saving a molar is
      4,268 pesetas.

PMID- 7711220
TI  - [Evaluation of program coverage of the hepatitis B vaccination in a school
      population. Navarra 1992-1993].
AB  - OBJECTIVE: To evaluate the coverage of the programme of control and coverage of
      Hepatitis B among children doing their 7th year of EGB (basic) in Navarra.
      DESIGN: Descriptive study. SETTING: School centres in Navarra. PARTICIPANTS: 7th
      year EGB students in the 1992-3 school year. INTERVENTION: Vaccination of the
      susceptible population with three doses of anti-HB vaccine on the 0-1-6 months
      pattern. MEASUREMENTS AND MAIN RESULTS: Nominal data of children vaccinated were
      obtained from 171 schools out of a total of 185 (92.43%). For the rest of the
      centres, it is known only that vaccinations took place within the School Health
      Programme. The susceptible population was 6,955 children, of whom 97.8% received
      the first dose, 97% the second and 95.6% the third. The most common cause of non
      vaccination in these children was lack of parental authorization, which reached
      1.8%. CONCLUSIONS: A School Health programme, which is well-established and
      closely linked to the Primary Care network, together with a broad diffusion of
      information about the adolescent Vaccination Programme were key to its widespread
      introduction and the excellent coverage attained.

PMID- 7711221
TI  - [Reporting of adverse drug reactions by primary care physicians].
AB  - OBJECTIVE: To study the contribution of Primary Care doctors to the understanding
      of adverse side-effects to drugs, through publication in the medical bibliography
      of cases of cough produced by Angiotensin-Converting-Enzyme (ACE) inhibitors.
      DESIGN: A retrospective observation study. SUBJECTS: The articles found in a
      bibliographic search through the data bases MEDLINE, Excerpta Medica and Indice
      Medico Espanol, all in CD-ROM, for the period 1982-1991. The notifications found
      of cases relating to cough produced by ACE inhibitors were evaluated through a
      minimum information data questionnaire. MEASUREMENTS AND MAIN RESULTS: A minimum
      information questionnaire was used. 119 cases of patients were found in 53
      articles. The average of authors and references per article was 2.88 and 8.54,
      respectively. The most frequent type of article was the letter, with Enalapril
      being the drug responsible for the cough in the majority of cases. All the
      articles studied included data from at least 6 of the minimum information items,
      the most common being: age, gender, dosage, reason for prescription, remission of
      the adverse reaction on stopping the medication and information on previous
      publications. Primary Care authors contributed more information in their articles
      than those authors who did not come from Primary Care. There is a statistically
      significant difference (p < 0.005) in the information items which refer to
      information on the presence of other illnesses and to the study of other
      pathological processes. CONCLUSIONS: The Primary Care authors published less
      cases of cough caused by ACE inhibitors, although their quality is similar to
      those from other sources. The information contributed which can be considered
      minimum was superior to that reviewed in previous studies.

PMID- 7711222
TI  - [Maternal participation to improve the effectiveness of diet education in
      children].
AB  - OBJECTIVE: To find out whether dietetic education in children improve its
      effectiveness with participation of mothers. DESIGN: We made a field try.
      SETTING: Two primary schools in Taco (La Laguna). SUBJECTS: We included every
      students who was in 7.o course in both schools (139 children). INTERVENTION: We
      assigned the children of one school to the educative intervention with mothers
      and the other school to the dietetic education without mothers. The intervention
      consist of four lectures about the fat food and the good feed. MEASUREMENTS AND
      MAIN RESULTS: We measured the dietetic knowledge with a questionnaire. And we
      made two plasmatic analysis to measure the lipidemia pre and postintervention. We
      excluded unauthorized children and those with more than one absence in our four
      classes. Both children groups showed a significative improvement in their
      knowledge (p < 0.05). The cholesterolaemia only decreased in the group with
      mothers (p = 0.01). It had a pradoxical diminishment of cholesterol HDL at the
      beginning was greater than 170 mg/dl, the reduction was more important yet in the
      group with mothers. CONCLUSIONS: The dietetic education can have variations in
      its effectiveness according the method employed and people who receive it. In the
      dietetic education of children the inclusion of mothers improve its
      effectiveness.

PMID- 7711223
TI  - [Social assessment of anxiety in primary health care].
AB  - OBJECTIVE: Identification of the social profile of our anxious patients, and
      analysis of the usefulness of Bell's questionnaire for our area of work. DESIGN:
      A retrospective observation study of a crossover type. SETTING: Primary Care.
      PARTICIPANTS: 55 patients who consulted their Family Doctor and were diagnosed as
      suffering from Anxiety. MEASUREMENTS AND MAIN RESULTS: We confirmed the diagnosis
      with the DSM-III-R and then analysed the level of Anxiety with the Hamilton
      Scale. The social evaluation was done by means of Bell's profile. As test
      statistics we used the lineal correlation Coefficient, the Student's t and Xi2
      tests and Variance Analysis. 65% of diagnoses were Generalised Anxiety. The
      Hamilton mean was 20.9 points (S = 9.2). Overall social adaptation was
      unsatisfactory, with the worst results being for the emotional aspects. We
      observed a higher level of Anxiety as age increased (p = 0.021), related to a
      worse adaptation to Health (p = 0.014). Dissatisfaction with work and the working
      environment took the form of professional adaptation being poorer as their work
      situation deteriorated (p = 0.006). Anxiety levels were higher among the
      unemployed. Social adaptation was less among people with higher Anxiety levels (p
      = 0.04), above all as a consequence of worse adaptation to Health (p = 0.002) and
      worse emotional (p = 0.00001) adaptation. CONCLUSIONS: 1) We must introduce
      social aspects into analysis of patients with Anxiety. 2) Bell's profile enables
      us to identify those social aspects which can be tackled when caring for our
      patients. Its fundamental use is in individual application.

PMID- 7711224
TI  - [Functional ability in people above 80 years old].
AB  - OBJECTIVE: To discover the functional capacity (CF) for population over 80 years
      assing to an health center. DESIGN: This was an observational crossover study,
      using OARS questionary. SETTING: An urban health center. PATIENTS AND OTHER
      PARTICIPANTS: A sex and residence proportional sample of aged 80 and over was
      taken from 1986 census registry. MEASUREMENTS AND MAIN RESULTS: To asses
      functional capacity we used ADL (Activities of daily living) dimension from OARS
      questionry. It's composed of 14 items, seven for basic activities of daily living
      (AVDb) and seven for instrumental activities (AVDi). We considered severe
      incapacity if the aged had some difficulty in one AVDb at lest; moderate
      incapacity if the showed only a trouble in some AVDi, and good CF if didn't show
      the least difficulty in any item. The 42.2% of aged had severe incapacity, 26% of
      population had got good CF. The most incapacity was watched in house-works and
      cooking; in the AVDb were sphincters and control and cleaniless corporal.
      CONCLUSIONS: Functional capacity in population aged in the zone is lightly
      inferior to the other studies, however the ages chosen aren't comparable
      absolutely. We find differences in functional capacity between sex, the results
      are better for men. Population aged who is living in institutions have mainly CF
      moderate, and the married are more good functional capacity than singles or
      widows.

PMID- 7711225
TI  - [Opinion of university professors on the suitability of specific primary care
      training in medical students].
AB  - OBJECTIVE: To find the opinion of teachers at the University of Alicante about
      the appropriateness of a Primary Care Theory-Practice programme within the
      Medicine curriculum. DESIGN: A descriptive observation study of a crossover
      nature. SETTING: Teachers of the Departments of Medicine and Public Health who
      had had contact with the Primary Care Theory-Practice programme. PARTICIPANTS: 44
      out of 71 teachers (62%) replied. INTERVENTION: An 11-question survey was
      answered anonymously between October 1993 and June 1994. MEASUREMENTS AND MAIN
      RESULTS: 77.3% (95% Confidence Interval 64.9-89.7%) considered appropriate the
      theoretical content at undergraduate level, where there was an average 18.5 hours
      teaching (C.I. 15.8-21.2); and 95.5% (C.I.89.4-100%), the practicals at a Health
      Centre, where there was an average 65.2 hours (C.I. 43.1-87.3) work. 43.9%
      thought it was appropriate to form a separate subject and 39% favored integrating
      these themes into other subjects. Theoretical contents would be basically
      teaching general information about Primary Care; and practical work would be
      clinical activities. The greatest advantages regarding carrying out practical
      work in Health Centres were: the student finds pathology more prevalent and
      learns to provide practical answers. The greatest disadvantages were: the low
      methodological knowledge and teaching preparation of the Teams. CONCLUSIONS:
      Those interviewed considered that the teaching at undergraduate level of a
      Primary Care subject with theoretical-practical content would be useful. The
      advantages, its contents and some difficulties were noted.

PMID- 7711226
TI  - [Bad habits of the Spanish language (and II). Pleonasms, solecisms, synecdoches,
      dehumanization, and other problems].

PMID- 7711227
TI  - [Prescription of exercise and physical activity in healthy people (I). General
      principles].

PMID- 7711228
TI  - [In defense of beta-adrenergic blockers].

PMID- 7711229
TI  - [Graphics and scientific communication].

PMID- 7711230
TI  - [The scooter: the ideal vehicle for primary care professionals? Opinion of 6
      users].

PMID- 7711231
TI  - The F0 complex of the ATP synthase of Escherichia coli contains a proton pathway
      with large proton polarizability caused by collective proton fluctuation.
AB  - The F0 complex of the Escherichia coli ATP synthase embedded into cardiolipin
      liposomes was studied by FT-IR spectroscopy. For comparison, respective studies
      were performed with dried F0 liposomes and with F0 liposomes treated with N,N'
      dicyclohexyl-carbodiimide (DCCD), which binds to Asp-61 of subunit c.
      Furthermore, the effect of H2O-->D2O exchange on the infrared spectrum was
      investigated. With F0 liposomes an infrared continuum is observed beginning at
      about 3000 cm-1 and extending toward smaller wavenumbers. In the DCCD-treated
      sample, this continuum is no longer observed. It vanishes also with drying of the
      liposomes. After H2O-->D2O exchange, this infrared continuum begins at about 2350
      cm-1 and is less intense. All of these results demonstrate that a proton pathway
      in native F0 is present, in which the protons are shifted in a hydrogen-bonded
      chain with large proton polarizability due to collective proton tunneling. With
      the D2O-hydrated system, deuteron polarizability due to collective deuteron
      motion is observed, but the polarizability due to collective deuteron motion is
      smaller. Such pathways are very efficient, because they conduct protons or
      deuterons within picoseconds. These pathways lose their polarizability if the F0
      complex is blocked by DCCD or if the liposomes are dried. On the basis of our
      results on the proton polarizability of hydrogen bonds and hydrogen-bonded
      systems and on the basis of structural data from the literature, the nature of
      the proton pathway of the F0 complex of E. coli is discussed.

PMID- 7711232
TI  - Multimodal action of single Na+ channels in myocardial mouse cells.
AB  - Unitary Na+ currents of myocardial mouse cells were studied at room temperature
      in 10 cell-attached patches, each containing one and only one channel. Small-pore
      patch pipettes (resistance 10-97 M omega when filled with 200% Tyrode's solution)
      with exceptionally thick walls were used. Observed were both rapidly inactivating
      (6 patches) and slowly inactivating (3 patches) Na+ currents. In one patch, a
      slow transition from rather fast to slow inactivation was detected over a time of
      0.5 h. A short and a long component of the open-channel life time were recorded
      at the beginning, but only a short one at the end of the experiment.
      Concomitantly, the first latency was slowed. Amplitude histograms showed that the
      electrochemical driving force across the pore of the channel did not change
      during this time. In three patches, a fast and repetitive switching between
      different modes of Na+ channel action could be clearly identified by plotting the
      long-time course of the averaged current per trace. The ensemble-averaged current
      formed in each mode was different in kinetics and amplitude. Each mode had a
      characteristic mean open-channel life time and distribution of first latency, but
      the predominant single-channel current amplitude was unaffected by mode switches.
      It is concluded that two types of changes in kinetics may happen in a single Na+
      channel: fast and reversible switches between different modes, and a slow loss of
      inactivation.

PMID- 7711233
TI  - Probability assessment of conformational ensembles: sugar repuckering in a DNA
      duplex in solution.
AB  - Conformational flexibility of molecules in solution implies that different
      conformers contribute to the NMR signal. This may lead to internal
      inconsistencies in the 2D NOE-derived interproton distance restraints and to
      conflict with scalar coupling-based torsion angle restraints. Such
      inconsistencies have been revealed and analyzed for the DNA octamer
      GTATAATG.CATATTAC, containing the Pribnow box consensus sequence. A number of
      subsets of distance restraints were constructed and used in the restrained Monte
      Carlo refinement of different double-helical conformers. The probabilities of
      conformers were then calculated by a quadratic programming algorithm, minimizing
      a relaxation rate-base residual index. The calculated distribution of conformers
      agrees with the experimental NOE data as an ensemble better than any single
      structure. A comparison with the results of this procedure, which we term PARSE
      (Probability Assessment via Relaxation rates of a Structural Ensemble), to an
      alternative method to generate solution ensembles showed, however, that the
      detailed multi-conformational description of solution DNA structure remains
      ambiguous at this stage. Nevertheless, some ensemble properties can be deduced
      with confidence, the most prominent being a distribution of sugar puckers with
      minor populations in the N-region and major populations in the S-region.
      Importantly, such a distribution is in accord with the analysis of independent
      experimental data--deoxyribose proton-proton scalar coupling constants.

PMID- 7711234
TI  - Integrated light-scattering spectroscopy, a sensitive probe for peptide-vesicle
      binding: application to the membrane-bound colicin E1 channel peptide.
AB  - Integrated light-scattering (ILS) spectroscopy was used to monitor the binding of
      the colicin E1 channel peptide to POPC:POPG large unilamellar vesicles (LUV;
      60:40, mol:mol) at acidic pH (3.5). Binding conditions were chosen such that
      nearly all of the channel peptide was bound to the vesicles with little free
      peptide remaining in solution. The increase in vesicle size upon the insertion of
      the channel peptide was measured by performing a discrete inversion technique on
      data obtained from an ILS spectrometer. Vesicle size number distributions were
      determined for five different systems having peptide/vesicle ratios of
      approximately 0, 77, 154, 206, and 257. The experiment was repeated four times
      (twice at two different vesicle concentrations) to determine reproducibility. The
      relative changes in vesicle radius upon peptide binding to the membrane vesicles
      was remarkably reproducible even though these changes represented only a few
      nanometers. A comparison of vesicle size number distributions in the absence of
      bound peptide was made between ILS and dynamic light scattering (DLS) data and
      showed similar results. However, DLS was incapable of detecting the small changes
      due to peptide-induced vesicle swelling. The membrane-bound volume of the colicin
      E1 channel peptide was approximately 177 +/- 22 nm3. These data indicate that in
      the absence of a membrane potential (closed channel state) the colicin E1 channel
      peptide inserts into the membrane resulting in a significant displacement of the
      lipid bilayer as evidenced from the dose-dependent increase in the vesicle
      radius. These results indicate that ILS spectroscopy is a sensitive sizing
      technique that is capable of detecting relatively small changes in membrane
      vesicles and may have a wide application in the determination of peptide binding
      to membrane vesicles.

PMID- 7711235
TI  - The mechanism of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor
      desensitization after removal of glutamate.
AB  - We have examined responses of AMPA (alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate) receptors in the chick nucleus magnocellularis to pairs of
      pulses of glutamate and determined the extent of desensitization and the rate of
      recovery. Receptors recovered from desensitization with a time constant of 16 ms,
      regardless of the concentration or duration of the conditioning pulse. Even with
      very brief conditioning pulses, evoking submaximal currents, desensitization
      occurred at a consistent rate after the removal of free ligand. A quantitative
      kinetic model based on these data shows that receptors must desensitize from a
      closed state. The results provide evidence that very brief exposure to glutamate,
      on the time scale of uniquantal synaptic transmission, will result in a
      significant reduction in sensitivity of postsynaptic receptors.

PMID- 7711236
TI  - Truncated K+ channel DNA sequences specifically suppress lymphocyte K+ channel
      gene expression.
AB  - We have constructed a series of deletion mutants of Kv1.3, a Shaker-like, voltage
      gated K+ channel, and examined the ability of these truncated mutants to form
      channels and to specifically suppress full-length Kv1.3 currents. These
      constructs were expressed heterologously in both Xenopus oocytes and a mouse
      cytotoxic T cell line. Our results show that a truncated mutant Kv1.3 must
      contain both the amino terminus and the first transmembrane-spanning segment, S1,
      to suppress full-length Kv1.3 currents. Amino-terminal-truncated DNA sequences
      from one subfamily suppress K+ channel expression of members of only the same
      subfamily. The first 141 amino acids of the amino-terminal of Kv1.3 are not
      necessary for channel formation. Deletion of these amino acids yields a current
      identical to that of full-length Kv1.3, except that it cannot be suppressed by a
      truncated Kv1.3 containing the amino terminus and S1. To test the ability of
      truncated Kv1.3 to suppress endogenous K+ currents, we constructed a plasmid that
      contained both truncated Kv1.3 and a selection marker gene (mouse CD4). Although
      constitutively expressed K+ currents in Jurkat (a human T cell leukemia line) and
      GH3 (an anterior pituitary cell line) cells cannot be suppressed by this double
      gene plasmid, stimulated (up-regulated) Shaker-like K+ currents in GH3 cells can
      be suppressed.

PMID- 7711237
TI  - Structural changes in Escherichia coli membranes induced by bacteriophage T4 at
      different temperatures.
AB  - This paper presents some further evidence for our model of DNA translocation into
      Escherichia coli cells by bacteriophage T4 (see Tarahovsky, Y. S., Khusainov, A.
      A., Deev, A. A., Kim, Y. V. 1991. FEBS Lett. 289:18-22). When lowering the
      temperature, we succeeded in slowing down the infection process and in observing
      a few separate stages by electron microscopy. Also, potassium leakage at
      different temperatures was measured. At 0-6 degrees C the phage was found to be
      irreversibly adsorbed on the cell surface, its tail to be contracted, and the
      outer membrane to be invaginated. Membrane fusion and formation of broad
      intermembrane bridges with a hole for potassium leakage were shown to start above
      7 degrees C. At about 17-20 degrees C the diameter of the bridge decreased
      considerably, which could correspond to the sealing of the membrane.

PMID- 7711238
TI  - Behavior of cholesterol and its effect on head group and chain conformations in
      lipid bilayers: a molecular dynamics study.
AB  - Cholesterol molecules were put into a computer-modeled hydrated bilayer of
      dimyristoyl phosphatidyl choline molecules, and molecular dynamics simulations
      were run to characterize the effect of this important molecule on membrane
      structure and dynamics. The effect was judged by observing differences in order
      parameters, tilt angles, and the fraction of gauche bonds along the hydrocarbon
      chains between lipids adjacent to cholesterol molecules and comparing them with
      those further away. It was observed that cholesterol causes an increase in the
      fraction of trans dihedrals and motional ordering of chains close to the rigid
      steroid ring system with a decrease in the kink population. The hydrogen-bonding
      interactions between cholesterol and lipid molecules were determined from radial
      distribution calculations and showed the cholesterol hydroxyl groups either
      solvated by water, or forming hydrogen bond contacts with the oxygens of lipid
      carbonyl and phosphate groups. The dynamics and conformation of the cholesterol
      molecules were investigated and it was seen that they had a smaller tilt with
      respect to the bilayer normal than the lipid chains and furthermore that the
      hydrocarbon tail of the cholesterol was conformationally flexible.

PMID- 7711239
TI  - The structure and stability of phospholipid bilayers by atomic force microscopy.
AB  - Atomic force microscopy (AFM) was used to investigate the structure, stability,
      and defects of the hydrophilic surfaces of Langmuir-Blodgett bilayer films of
      distearoylphosphatidylcholine (DSPC) and dipalmitoylphosphatidylethanolamine
      (DPPE) in the solid phase, and dilinoleoylphosphatidylethanolamine (DLPE) in the
      fluid phase. Their relative resilience to external mechanical stress by the
      scanning tip and by fluid exchange were also investigated. DPPE monolayers showed
      parallel ridges at the surface with a period of 0.49 nm, corresponding to the
      rows of aligned headgroups consistent with the known crystallographic structure.
      DSPC and DLPE monolayers did not show any periodic order. The solid DSPC and DPPE
      monolayers were stable to continued rastering by the AFM tip; however, the
      stability of DLPE monolayers depended on the pH of the aqueous environment.
      Structural defects in the form of monolayer gaps and holes were observed after
      fluid exchange, but the defects in DLPE monolayer at pH 11 were stable during
      consecutive scanning. At pH 9 and below, the defects induced by fluid exchange
      over DLPE monolayers were more extensive and were deformed easily by consecutive
      scanning of the AFM tip at a force of 10 nN. The pH dependence of resilience was
      explained by the increasing bending energy or frustration due to the high
      spontaneous curvature of DLPE monolayers at low pH. The tangential stress exerted
      by the AFM tip on the deformable monolayers eventually produced a ripple pattern,
      which could be described as a periodic buckling known as Shallamach waves.

PMID- 7711240
TI  - Glycosphingolipid fatty acid arrangement in phospholipid bilayers: cholesterol
      effects.
AB  - Deuterium wide line NMR spectroscopy was used to study cholesterol effects on the
      ceramide portions of two glycosphingolipids (GSLs) distributed as minor
      components in fluid membranes. The common existence of very long fatty acids on
      GSLs was taken into account by including one glycolipid species with fatty acid
      chain length matching that of the host matrix, and one longer by 6 carbons. N
      stearoyl and N-lignoceroyl galactosyl ceramide with perdeuterated fatty acid
      (18:0[d35] GalCer and 24:0[d47] GalCer) were prepared by partial synthesis. They
      were dispersed in bilayer membranes having the 18-carbon-fatty-acid phospholipid,
      1-stearoyl-2-oleoyl-phosphatidylcholine (SOPC), as major component. Glycolipid
      fatty acid chain behavior and arrangement were analyzed using order profiles
      derived from their 2H-NMR spectra. Cholesterol effects on order parameter
      profiles for 18:0[d35] GalCer, with chain length equal to that of the host
      matrix, followed the pattern known for acyl chains of phospholipids. The presence
      of sterol led to restriction of trans/gauche isomerization along the length of
      the chain, with the largest absolute increase in order parameters being toward
      the surface, but somewhat greater relative effect just below the "plateau"
      region. In cholesterol-containing membranes, order parameter profiles for the
      long chain species, 24:0[d47] GalCer, showed a characteristic secondary "plateau"
      associated with carbon atoms C14 to C23, a feature also present in SOPC bilayers
      without cholesterol and in pure hydrated 24:0[d47] GalCer. Cholesterol-induced
      ordering effects on the long chain glycolipid were similar to those described for
      the shorter chain species, but were minimal at the methyl terminus. Within a
      given membrane,SCD profiles for 1 8:O[d3] GalCer and 24:0[d47] GalCer were
      quantitatively similar to a membrane depth of C13 to C14. SCD values at C16 and
      C17 were about 15% and 28% higher, respectively, for the long chain GSL than for
      its short chain analogue inSOPC/cholesterol (compared to 21 and 31%,
      respectively, in membranes without cholesterol). Nitroxide spin labels attached
      rigidly to C16 of the long chain glycolipid gave EPR order parameters that were
      twice as high as for the same spin label at C16 on the shorter chain glycolipid
      in both matrices. It would appear that the above factors impose a tendency for
      the "extra" portion of the 24-carbon chain to cross the bilayer midplane where it
      may interact with terminal portions of acyl chains in the opposing monolayer;
      however, steric constraints, and probably collision events associated with
      lateral diffusion, induce wide orientation fluctuations in the segment involved.

PMID- 7711241
TI  - Modulation of melittin-induced lysis by surface charge density of membranes.
AB  - Phosphorus NMR spectroscopy was used to characterize the importance of
      electrostatic interactions in the lytic activity of melittin, a cationic peptide.
      The micellization induced by melittin has been characterized for several lipid
      mixtures composed of saturated phosphatidylcholine (PC) and a limited amount of
      charged lipid. For these systems, the thermal polymorphism is similar to the one
      observed for pure PC: small comicelles are stable in the gel phase and extended
      bilayers are formed in the liquid crystalline phase. Vesicle surface charge
      density influences strongly the micellization. Our results show that the presence
      of negatively charged lipids (phospholipid or unprotonated fatty acid) reduces
      the proportion of lysed vesicles. Conversely, the presence of positively charged
      lipids leads to a promotion of the lytic activity of the peptide. The modulation
      of the lytic effect is proposed to originate from the electrostatic interactions
      between the peptide and the bilayer surface. Attractive interactions anchor the
      peptide at the surface and, as a consequence, inhibit its lytic activity.
      Conversely, repulsive interactions favor the redistribution of melittin into the
      bilayer, causing enhanced lysis. A quantitative analysis of the interaction
      between melittin and negatively charged bilayers suggests that electroneutrality
      is reached at the surface, before micellization. The surface charge density of
      the lipid layer appears to be a determining factor for the lipid/peptide
      stoichiometry of the comicelles; a decrease in the lipid/peptide stoichiometry in
      the presence of negatively charged lipids appears to be a general consequence of
      the higher affinity of melittin for these membranes.

PMID- 7711242
TI  - Molecular properties of a stratum corneum model lipid system: large unilamellar
      vesicles.
AB  - Stratum corneum lipids are relatively complex, and there is little detailed
      understanding of their chemical and physical properties at the molecular level.
      Large unilamellar vesicles (LUVs) with lipid compositions similar to those of
      stratum corneum were prepared at pH 9 with commercially available lipids. This
      system was used as a model system for molecular studies of stratum corneum
      lipids. LUVs were chosen as the model system as they are comparatively more
      stable and can be characterized more quantitatively in terms of lipid
      concentration, surface area, and volume than model systems such as lipid mixture
      suspensions, lipid films, and small unilamellar vesicles. Results from freeze
      fracture and cryo electron microscopy studies of our LUVs showed spherical
      vesicles. Quasi-elastic light scattering measurements revealed a narrow size
      distribution, centering around 119 nm. At room temperature, the LUVs were stable
      for several weeks at pH 9 and for more than 15 h but less than 24 h at pH 6.
      Differential scanning calorimetry measurements indicated broad endothermic
      transitions centered near 60-65 degrees C, closely matching the transition
      temperature reported for stratum corneum lipid extracts. Spin probes, 5
      doxylstearic acid and 12-doxylstearic acid, were used for electron paramagnetic
      resonance (EPR) studies of the molecular dynamics of the lipids. EPR results
      indicated more restricted motion near the polar headgroup region than near the
      center of the alkyl chain region. Motional profiles of the spin labels near the
      polar headgroup and within the alkyl chain region in the LUVs were obtained as a
      function of temperature, ranging from 25 to 90 degrees C. We also found that the
      partitioning between the lipid and aqueous phases for each spin probe was
      temperature dependent and was generally correlated with phase transitions
      observed by differential scanning calorimetry and with alkyl chain mobility
      observed by EPR. Thus, this LUV system is well suited for additional molecular
      studies under different experimental conditions.

PMID- 7711243
TI  - Self-association accompanies inhibition of Ca-ATPase by thapsigargin.
AB  - Recent studies have demonstrated a relationship between the activity of the Ca
      ATPase of sarcoplasmic reticulum and its state of self-association. In the
      present study, the effects of thapsigargin (TG), a toxin that specifically
      inhibits the Ca-ATPase of rabbit skeletal muscle sarcoplasmic reticulum membrane,
      were studied by detecting the time-resolved phosphorescence anisotropy (TPA)
      decay of the Ca-ATPase that had been labeled with the phosphorescent probe
      erythrosin-isothiocyanate (ErITC). Anisotropy decays were fit to a function that
      consisted of three exponential decays plus a constant background, as well as to a
      function describing explicitly the uniaxial rotation of proteins in a membrane.
      In the absence of TG, the anisotropy was best-fit by a model representing the
      rotation of three populations, corresponding to different-sized oligomeric
      species in the membrane. The addition of stoichiometric amounts of TG to the Ca
      ATPase promptly decreased the overall apparent rate of decay, indicating
      decreased rotational mobility. A detailed analysis showed that the principal
      change was not in the rates of rotation but rather in the population distribution
      of the Ca-ATPase molecules among the different-sized oligomers. TG decreased the
      proportion of small oligomers and increased the proportion of large ones.
      Preincubation of the ErITC-SR in 1 mM Ca2+, which stabilizes the E1 conformation
      relative to E2, was found to protect partially against the changes in the TPA
      associated with the presence of the inhibitor. These results are consistent with
      the hypothesis that TG inhibits the Ca-ATPase by stabilizing it in an E2-like
      conformation, which promotes the formation of larger aggregates of the enzyme.
      When combined with the effects of other inhibitors on the Ca-ATPase, these
      results support a general model for the coupling of enzyme conformation and self
      association in this system.

PMID- 7711244
TI  - Inhibition of muscle force by vanadate.
AB  - Vanadate (Vi), an analogue of inorganic phosphate (Pi), is known to bind tightly
      with a long half life to the myosin MgATPase site, producing a complex which
      inhibits force. Both of these ligands bind to an actin.myosin.ADP state that
      follows the release of Pi in the enzymatic cycle, and their effects on muscle
      fibers and proteins in solution provide information on the properties of this
      state. The inhibition of active force generation began to occur at a [Vi] of 5
      microM and was 90% complete at a [Vi] of 1 mM. Hill plots of the inhibition of
      force by Vi approximated that expected for a simple binding isotherm. Similar
      plots were obtained at both 25 degrees C and 5 degrees C. A simple binding
      isotherm is not expected to occur in a muscle fiber where steric constraints
      imposed by the intact filaments should introduce more complexity into the
      energetics of ligand binding. The inhibition of MgATPase activity for acto
      subfragment-1 to 50% of controls occurred at a [Vi] which was only 20-fold higher
      than that required to inhibit force generation in fibers to the same level. Some
      models of actomyosin interactions would predict that the range of [Vi] required
      for complete force inhibition in fibers and the difference in the [Vi] required
      for inhibition in fibers and of myosin in solution would both be much larger.

PMID- 7711245
TI  - Effect of stretch and release on equatorial X-ray diffraction during a twitch
      contraction of frog skeletal muscle.
AB  - Time-resolved intensity measurements of the x-ray equatorial reflections were
      made during twitch contractions of frog skeletal muscles, to which stretches or
      releases were applied at various times. A ramp stretch applied at the onset of a
      twitch (duration, 15 ms; amplitude, approximately 3% of muscle length) caused a
      faster and larger development of contractile force than in an isometric twitch.
      The stretch accelerated the decrease of the 1.0 reflection intensity (I1,0). The
      magnitude of increase of the 1,1 reflection intensity (I1,1) was reduced by the
      stretch, but its time course was also accelerated. A release applied at the peak
      of a twitch or later (duration, 5 ms; amplitude, approximately 1.5%) caused only
      a partial redevelopment of tension. The release produced clear reciprocal changes
      of reflections toward their relaxed levels, i.e., the I1,0 increased and the I1,1
      decreased. A release applied earlier than the twitch peak had smaller effects on
      the reflection intensities. The results suggest that a strength applied at the
      onset of a twitch causes a faster radial movement of the myosin heads toward
      actin, whereas a release applied at or later than the peak of a twitch
      accelerates their return to the thick filament backbone. The results are
      discussed in the context of the regulation of the myosin head attachment by
      calcium.

PMID- 7711246
TI  - Faster force transient kinetics at submaximal Ca2+ activation of skinned psoas
      fibers from rabbit.
AB  - The early, rapid phase of tension recovery (phase 2) after a step change in
      sarcomere length is thought to reflect the force-generating transition of myosin
      bound to actin. We have measured the relation between the rate of tension
      redevelopment during phase 2 (r), estimated from the half-time of tension
      recovery during phase 2 (r = t0.5(-1)), and steady-state force at varying [Ca2+]
      in single fibers from rabbit psoas. Sarcomere length was monitored continuously
      by laser diffraction of fiber segments (length approximately 1.6 mm), and
      sarcomere homogeneity was maintained using periodic length release/restretch
      cycles at 13-15 degrees C. At lower [Ca2+] and forces, r was elevated relative to
      that at pCa 4.0 for both releases and stretches (between +/- 8 nm). For releases
      of -3.4 +/- 0.7 nm.hs-1 at pCa 6.6 (where force was 10-20% of maximum force at
      pCa 4.0), r was 3.3 +/- 1.0 ms-1 (mean +/- SD; N = 5), whereas the corresponding
      value of r at pCa 4.0 was 1.0 +/- 0.2 ms-1 for releases of -3.5 +/- 0.5 nm.hs-1
      (mean +/- SD; N = 5). For stretches of 1.9 +/- 0.7 nm.hs-1, r was 1.0 +/- 0.3 ms
      1 (mean +/- SD; N = 9) at pCa 6.6, whereas r was 0.4 +/- 0.1 ms-1 at pCa 4.0 for
      stretches of 1.9 +/- 0.5 (mean +/- SD; N = 14). Faster phase 2 transients at
      submaximal Ca(2+)-activation were not caused by changes in myofilament lattice
      spacing because 4% Dextran T-500, which minimizes lattice spacing changes, was
      present in all solutions. The inverse relationship between phase 2 kinetics and
      force obtained during steady-state activation of skinned fibers appears to be
      qualitatively similar to observations on intact frog skeletal fibers during the
      development of tetanic force. The data are consistent with models that
      incorporate a direct effect of [Ca2+] on phase 2 kinetics of individual cross
      bridges or, alternatively, in which phase 2 kinetics depend on cooperative
      interactions between cross-bridges.

PMID- 7711247
TI  - Strain sensitivity and turnover rate of low force cross-bridges in contracting
      skeletal muscle fibers in the presence of phosphate.
AB  - Inorganic phosphate (Pi) decreases the isometric tension of skinned skeletal
      muscle fibers, presumably by increasing the relative fraction of a low force
      quaternary complex of actin, myosin, ADP, and Pi (A.M.ADP.Pi). At the same time,
      Pi gives rise to a fast relaxing mechanical component as detected by oscillations
      at 500 Hz. To characterize the dynamic properties of this A.M.ADP.Pi complex, the
      effect of Pi on the tension response to stretch was investigated with rabbit
      psoas fibers. A ramp stretch applied in the presence of 20 mM Pi increased
      tension more than in the control solution (0 mM Pi) but reduced the fast relaxing
      component to the control level. Thus, a stretch seems to convert the low force,
      fast relaxing A.M.ADP.Pi complex to a high force, slow relaxing form. However,
      the Pi-induced enhancement of the tension response was not observed until the
      fibers were stretched more than 0.4% of their length, suggesting that a critical
      cross-bridge extension of approximately 4 nm is required for this conversion. The
      rate constant of the attachment/detachment of this low force complex was
      estimated from the velocity dependence of the enhancement. It was approximately
      10 s-1, in marked contrast to the A.M.ADP.Pi complex under low salt, relaxed
      conditions (approximately 10,000 s-1). The enhancement of the tension response
      was not observed when isometric tension was reduced by lowering free calcium,
      implying that calcium and Pi affect different steps in the actomyosin ATPase
      cycle during contraction.

PMID- 7711248
TI  - Functional interactions in bacteriorhodopsin: a theoretical analysis of retinal
      hydrogen bonding with water.
AB  - The light-driven proton pump, bacteriorhodopsin (bR) contains a retinal molecule
      with a Schiff base moiety that can participate in hydrogen-bonding interactions
      in an internal, water-containing channel. Here we combine quantum chemistry and
      molecular mechanics techniques to determine the geometries and energetics of
      retinal Schiff base-water interactions. Ab initio molecular orbital calculations
      are used to determine potential surfaces for water-Schiff base hydrogen-bonding
      and to characterize the energetics of rotation of the C-C single bond distal and
      adjacent to the Schiff base NH group. The ab initio results are combined with
      semiempirical quantum chemistry calculations to produce a data set used for the
      parameterization of a molecular mechanics energy function for retinal. Using the
      molecular mechanics force field the hydrated retinal and associated bR protein
      environment are energy-minimized and the resulting geometries examined. Two
      distinct sites are found in which water molecules can have hydrogen-bonding
      interactions with the Schiff base: one near the NH group of the Schiff base in a
      polar region directed towards the extracellular side, and the other near a
      retinal CH group in a relatively nonpolar region, directed towards the
      cytoplasmic side.

PMID- 7711249
TI  - Helical stacking in DNA three-way junctions containing two unpaired pyrimidines:
      proton NMR studies.
AB  - The proton NMR spectra of DNA three-way junction complexes (TWJ) having unpaired
      pyrimidines, 5'-TT- and 5'-TC- on one strand at the junction site were assigned
      from 2D NOESY spectra acquired in H2O and D2O solvents and homonuclear 3D NOESY
      TOCSY and 3D NOESY-NOESY in D2O solvent. TWJ are the simplest branched structures
      found in biologically active nucleic acids. Unpaired nucleotides are common
      features of such structures and have been shown to stabilize junction formation.
      The NMR data confirm that the component oligonucleotides assemble to form
      conformationally homogeneous TWJ complexes having three double-helical, B-form
      arms. Two of the helical arms stack upon each other. The unpaired pyrimidine
      bases lie in the minor groove of one of the helices and are partly exposed to
      solvent. The coaxial stacking arrangement deduced is different from that
      determined by Rosen and Patel (Rosen, M.A., and D.J. Patel. 1993. Biochemistry.
      32:6576-6587) for a DNA three-way junction having two unpaired cytosines, but
      identical to that suggested by Welch et al. (Welch, J. B., D. R. Duckett, D. M.
      J. Lilley. 1993. Nucleic Acids Res. 21:4548-4555) on the basis of gel
      electrophoretic studies of DNA three-way junctions containing unpaired adenosines
      and thymidines.

PMID- 7711250
TI  - Refinement of the solution structure of a branched DNA three-way junction.
AB  - We have refined the structure of the DNA Three-Way Junction complex, TWJ-TC,
      described in the companion paper by quantitative analysis of two 2D NOESY spectra
      (mixing times 60 and 200 ms) obtained in D2O solution. NOESY crosspeak
      intensities extracted from these spectra were used in two kinds of refinement
      procedure: 1) distance-restrained energy minimization (EM) and molecular dynamics
      (MD) and 2) full relaxation matrix back calculation refinement. The global
      geometry of the refined model is very similar to that of a published, preliminary
      model (Leontis, 1993). Two of the helical arms of the junction are stacked. These
      are Helix 1, defined by basepairs S1-G1/S3-C12 through S1-C5/S3-G8 and Helix 2,
      which comprises basepairs S1-C6/S2-G5 through S1-G10/S2-G1. The third helical arm
      (Helix 3), comprised of basepairs S2-C6/S3-G5 through S2-C10/S3-G1 extends almost
      perpendicularly from the axis defined by Helices 1 and 2. The bases S1-C5 and S1
      C6 of Strand 1 are continuously stacked across the junction region. The
      conformation of this strand is close to that of B-form DNA along its entire
      length, including the S1-C5 to S1-C6 dinucleotide step at the junction. The two
      unpaired bases S3-T6 and S3-C7 lie outside of the junction along the minor groove
      of Helix 1 and largely exposed to solvent. Analysis of the refined structure
      reveals that the glycosidic bond of S3-T6 exists in the syn conformation,
      allowing the methyl group of this residue to contact the hydrophobic surface of
      the minor groove of Helix 1, at S3-G11. The helical parameters of the three
      helical arms of the structure exhibit only weak deviations from typical values
      for right-handed B-form DNA. Unusual dihedral angles are only observed for the
      sugarphosphate backbone joining the "hinge" residues, S2-G5 and S2-C6, and S3-G5
      through S3-G8. The glycosidic bond of S3-G8also lies within the syn range,
      allowing favorable Watson-Crick base-pairing interactions with Si -C5. The
      stability of this structure was checked in 39 ps molecular dynamic simulation at
      330 K in water. The structure of TWJ-TC retained the geometrical features
      mentioned above at the end of the simulation period. The final R(1/6)-factor of
      the refined structure is 5%.

PMID- 7711251
TI  - Volume contraction on photoexcitation of the reaction center from Rhodobacter
      sphaeroides R-26: internal probe of dielectrics.
AB  - Reaction centers of Rhodobacter sphaeroides undergo a approximately 20 A3/mole
      volume contraction in < 50 ns after excitation. The rapid volume change is
      tentatively assigned to electrostriction. From its magnitude, we infer that the
      effective dielectric coefficient is 10-15 if the compressibility of the reaction
      center is similar to that of globular proteins. The volume contraction is not
      sensitive to replacement of the natural ubiquinone at the QA site by other
      quinones or to the occupancy of the QB site. The quenching caused by pressure on
      the reaction centers most likely occurs on a faster time scale than that of
      electron transfer.

PMID- 7711252
TI  - Triplet and fluorescing states of the CP47 antenna complex of photosystem II
      studied as a function of temperature.
AB  - Fluorescence emission and triplet-minus-singlet (T-S) absorption difference
      spectra of the CP47 core antenna complex of photosystem II were measured as a
      function of temperature and compared to those of chlorophyll a in Triton X-100.
      Two spectral species were found in the chlorophyll T-S spectra of CP47, which may
      arise from a difference in ligation of the pigments or from an additional
      hydrogen bond, similar to what has been found for Chl molecules in a variety of
      solvents. The T-S spectra show that the lowest lying state in CP47 is at
      approximately 685 nm and gives rise to fluorescence at 690 nm at 4 K. The
      fluorescence quantum yield is 0.11 +/- 0.03 at 4 K, the chlorophyll triplet yield
      is 0.16 +/- 0.03. Carotenoid triplets are formed efficiently at 4 K through
      triplet transfer from chlorophyll with a yield of 0.15 +/- 0.02. The major decay
      channel of the lowest excited state in CP47 is internal conversion, with a
      quantum yield of about 0.58. Increase of the temperature results in a broadening
      and blue shift of the spectra due to the equilibration of the excitation over the
      antenna pigments. Upon increasing the temperature, a decrease of the fluorescence
      and triplet yields is observed to, at 270 K, a value of about 55% of the low
      temperature value. This decrease is significantly larger than of chlorophyll a in
      Triton X-100. Although the coupling to low-frequency phonon or vibration modes of
      the pigments is probably intermediate in CP47, the temperature dependence of the
      triplet and fluorescence quantum yield can be modeled using the energy gap law in
      the strong coupling limit of Englman and Jortner (1970. J. Mol. Phys. 18:145-164)
      for non-radiative decays. This yields for CP47 an average frequency of the
      promoting/accepting modes of 350 cm-1 with an activation energy of 650 cm-1 for
      internal conversion and activationless intersystem crossing to the triplet state
      through a promoting mode with a frequency of 180 cm-1. For chlorophyll a in
      Triton X-100 the average frequency of the promoting modes for non-radiative decay
      is very similar, but the activation energy (300 cm-1) is significantly smaller.

PMID- 7711253
TI  - Solution nonideality related to solute molecular characteristics of amino acids.
AB  - By measuring the freezing-point depression for dilute, aqueous solutions of all
      water-soluble amino acids, we test the hypothesis that nonideality in aqueous
      solutions is due to solute-induced water structuring near hydrophobic surfaces
      and solute-induced water destructuring in the dipolar electric fields generated
      by the solute. Nonideality is expressed with a single solute/solvent interaction
      parameter I, calculated from experimental measure of delta T. A related
      parameter, I(n), gives a method of directly relating solute characteristics to
      solute-induced water structuring or destructuring. I(n)-values correlate directly
      with hydrophobic surface area and inversely with dipolar strength. By comparing
      the nonideality of amino acids with progressively larger hydrophobic side chains,
      structuring is shown to increase with hydrophobic surface area at a rate of one
      perturbed water molecule per 8.8 square angstroms, implying monolayer coverage.
      Destructuring is attributed to dielectric realignment as described by the Debye
      Huckel theory, but with a constant separation of charges in the amino-carboxyl
      dipole. By using dimers and trimers of glycine and alanine, this destructuring is
      shown to increase with increasing dipole strength using increased separation of
      fixed dipolar charges. The capacity to predict nonideal solution behavior on the
      basis of amino acid characteristics will permit prediction of free energy of
      transfer to water, which may help predict the energetics of folding and unfolding
      of proteins based on the characteristics of constituent amino acids.

PMID- 7711254
TI  - Polysaccharide helices in the atomic force microscope.

PMID- 7711255
TI  - Characterization of enzyme-bound ligand dynamics by solid-state NMR in the
      presence of ligand exchange: L-phenylalanine on carboxypeptidase A.
AB  - Deuterium NMR spectra were obtained for L-phenylalanine-d5, deuterated on the
      phenyl ring, in cross-linked polycrystalline samples of carboxypeptidase A
      containing different amounts of water. The deuterium powder pattern line shapes
      are simulated by extension of the theory to include both a local reorientational
      motion of the bound L-phenylalanine phenyl ring and exchange of the L
      phenylalanine with an intracrystalline isotropic environment. The spectral
      simulations are consistent with the phenyl ring of the phenylalanine executing pi
      flips in the bound environment at rates that vary from 3 x 10(4) Hz at 6% water
      content to 1 x 10(5) Hz at 21% water content. At all water contents studied, the
      ligand exchanges with an essentially isotropic environment in the crystal with a
      rate constant of approximately 2.5 x 10(-3) Hz. Although the dissociation
      constant for the L-phenylalanine is only 18 mM, the spectral simulations that
      reproduce the experimental line shape well do not require significant wobble of
      the phenyl ring rotation axis, which is consistent with the binding interactions
      identified by x-ray crystallography.

PMID- 7711256
TI  - X-ray diffraction of a protein crystal anchored at the air/water interface.
AB  - We report the first successful in situ x-ray diffraction experiment with a 2D
      protein array at the lipid/water interface and demonstrate that the order can be
      controlled via lateral pressure or density. A protein (streptavidin) was bound to
      a monolayer of biotinylated lipid at the air/water interface, and diffraction of
      the protein layer could be measured to many orders. Compression of the monolayer
      changed the diffraction pattern drastically, indicating that the protein
      structure can be strongly influenced by external parameters like lateral pressure
      or density. From the width of the peaks, we find that aggregates consisting of as
      few as 100 monomers contribute to the diffraction. This indicates that the
      structure of even low order aggregates can be studied in situ. Grazing incidence
      diffraction can become a strong new method to study the crystallization and the
      interactions between proteins free from artifacts by staining or sample
      preparation.

PMID- 7711257
TI  - Micropipette manipulation technique for the monitoring of pH-dependent membrane
      lysis as induced by the fusion peptide of influenza virus.
AB  - We have assembled a micropipette aspiration assay to measure membrane
      destabilization events in which large (20-30 microns diameter) unilamellar
      vesicles are manipulated and exposed to membrane destabilizing agents. Single
      events can be seen with a light microscope and are recorded using both a video
      camera and a photomultiplier tube. We have performed experiments with a wild-type
      fusion peptide from influenza virus (X31) and found that it induces pH-dependent,
      stochastic lysis of large unilamellar vesicles. The rate and extent of lysis are
      both maximum at pH 5; the maximum rate of lysis is 0.018 s-1 at pH 5. An analysis
      of our data indicates that the lysis is not correlated either to the size of the
      vesicles or to the tension created in the vesicle membranes by aspiration.

PMID- 7711258
TI  - Nanosecond optical rotatory dispersion spectroscopy: application to photolyzed
      hemoglobin-CO kinetics.
AB  - A standard technique for static optical rotatory dispersion (ORD) measurements is
      adapted to the measurement of ORD changes on a nanosecond (ns) time scale, giving
      approximately a million-fold improvement in time-resolution over conventional
      instrumentation. The technique described here is similar in principle to a
      technique recently developed for ns time-resolved circular dichroism (TRCD)
      spectroscopy, although the time-resolved optical rotatory dispersion (TRORD)
      technique requires fewer optical components. As with static ORD, TRORD
      measurements may be interpreted by empirical comparisons or may be transformed,
      via the Kramers-Kronig relations, to more easily interpreted TRCD spectra. TRORD
      can offer experimental advantages over TRCD in studying kinetic processes
      effecting changes in the chiral structures of biological molecules. In
      particular, the wider dispersion of ORD bands compared with the corresponding CD
      bands means that ORD information may often be obtained outside of absorption
      bands, a signal-to-noise advantage for multichannel measurements. Demonstration
      of the technique by its application to ns TRORD and the transform-calculated TRCD
      of carboxy-hemoglobin (Hb-CO) after laser photolysis is presented.

PMID- 7711259
TI  - Aggregation of chlorophyll a probed by resonance light scattering spectroscopy.
AB  - We report the resonance light scattering (RLS) spectra of chlorophyll a
      aggregated in a 9:1 solution of formamide and pH 6.8 phosphate buffer. The
      aggregate formed after 2 h of mixing, referred to as Chl469, shows a strong
      scattering feature at 469 nm (Soret band) and a much weaker feature at 699 nm (Qy
      band). A kinetic investigation confirmed that the aggregation process is
      cooperative, and also detected one intermediate (Chl458) with a strong RLS
      spectrum but only a weak CD spectrum. We propose that aggregation proceeds via at
      least three steps: 1) formation of a nucleating species, probably a dimer of
      chlorophylls; 2) formation of large aggregates with little or no secondary
      structure (e.g., Chl458); and 3) conformational change to form helical aggregate
      (Chl469).

PMID- 7711260
TI  - Metal-ligand complexes as a new class of long-lived fluorophores for protein
      hydrodynamics.
AB  - We describe the use of asymmetric Ru-ligand complexes as a new class of
      luminescent probes that can be used to measure rotational motions of proteins.
      These complexes are known to display luminescent lifetimes ranging from 10 to
      4000 ns. In this report, we show that the asymmetric complex Ru(bpy)2(dcbpy)
      (PF6)2 displays a high anisotropy value when excited in the long wavelength
      absorption band. For covalent linkage to proteins, we synthesized the N-hydroxy
      succinimide ester of this metal-ligand complex. To illustrate the usefulness of
      these probes, we describe the intensity and anisotropy decays of
      [Ru(bpy)2(dcbpy)] when covalently linked to human serum albumin, concanavalin A
      (ConA), human immunoglobulin G (IgG), and Ferritin, and measured in solutions of
      increased viscosity. These data demonstrate that the probes can be used to
      measure rotational motions on the 10 ns to 1.5 microseconds timescale, which so
      far has been inaccessible using luminescence methods. The present probe
      [Ru(bpy)2(dcbpy)] can be regarded as the first of a class of metal-ligand
      complexes, each with different chemical reactivity and spectral properties, for
      studies of macromolecular dynamics.

PMID- 7711261
TI  - Induced conformational states of amphipathic peptides in aqueous/lipid
      environments.
AB  - Specific conformational effects have been reported for amphipathic model peptides
      upon binding of defined hydrophobic domains to nonpolar stationary phases during
      reversed-phase high performance liquid chromatography (RP-HPLC). Such induced
      conformations are found to be especially pronounced for peptides that are
      amphipathic in an alpha-helical conformation. Such induced amphipathic
      conformations resulted in substantially later elution than predicted using amino
      acid-based retention coefficients. In the present study, the induced
      conformational behavior of model peptides observed during RP-HPLC was correlated
      with their secondary structure as determined by circular dichroism (CD)
      spectroscopy in both aqueous solution and C18-mimetic environments. The
      experimental retention times of the peptides studied were found to correlate with
      their CD spectra in the presence of lipids, whereas a poor correlation was
      observed with their CD spectra in the presence of trifluoroethanol. A new
      approach was developed to evaluate the induction of secondary structure in
      peptides due to interactions at aqueous/lipid interfaces, which involves the
      measurement of the CD ellipticities of peptides bound to a set of C18-coated
      quartz plates. An excellent correlation was found in this environment between the
      RP-HPLC retention times and CD ellipticities of the bound peptides.

PMID- 7711262
TI  - Observation of the helical structure of the bacterial polysaccharide acetan by
      atomic force microscopy.
AB  - A method has been developed that has been found to give reproducible images of
      uncoated polysaccharides by Atomic Force Microscopy (AFM). Aqueous solutions of
      the polysaccharide are deposited as drops onto freshly cleaved mica surfaces, air
      dried, and then imaged under butanol. The method has been used to obtain images
      of the bacterial polysaccharide acetan. In regions within the deposited sample,
      where the molecules are aligned side-by-side, it has been possible to observe a
      periodic structure along the polysaccharide chain, attributable to the helical
      structure of acetan.

PMID- 7711263
TI  - Electrorotation measurements of diamide-induced platelet activation changes.
AB  - Electrorotation is a special dielectric spectroscopic technique capable of
      measuring the polarizability of single platelets. The rotational speed of the
      particles is recorded as a function of the frequency of the applied rotating
      electric field. As previously shown, the speed of electrorotation in the range of
      the first characteristic frequency (anti-field rotation) decreased upon
      activation and was correlated with [14C]serotonin release and an increase of the
      TMA-DPH-induced fluorescence. Diamide upon activation and was correlated with
      [14C]serotonin release and an increase of the TMA-DPH-induced fluorescence.
      Diamide incubation induced morphological changes in control platelets. These
      changes were accompanied by a shift of the first characteristic frequency of
      electrorotation toward higher values and a parallel increase of the anti-field
      rotation. This was explained by a decrease of membrane conductivity and by the
      changed polarizability of platelet interior due to the observed internal platelet
      structure changes. Diamide inhibited activation assessed by both electrorotation
      and TMA-DPH fluorescence in the case of all activators except the ionophore A
      23187. Because diamide largely inhibited the A 23187-induced serotonin release,
      it was concluded that, despite the diamide treatment, the direct increase of
      cytoplasmic Ca2+ was still able to induce membrane conductivity changes
      accessible by electrorotation, but this did not complete the final release step
      of the activation process.

PMID- 7711264
TI  - Time course of release of catecholamines from individual vesicles during
      exocytosis at adrenal medullary cells.
AB  - The time course of extrusion of the vesicular contents during exocytosis has been
      examined at adrenal medullary cells with carbon-fiber microelectrodes. Two
      electrochemical techniques were used: cyclic voltammetry and amperometry. Spikes
      obtained by amperometry had a faster time course than those measured by cyclic
      voltammetry, consistent with the different concentration profiles established by
      each technique. However, the experimental data obtained with both techniques were
      temporally broadened with respect to dispersion of an instantaneous point source
      by diffusion. Measurements with the electrode firmly pressed against the cell
      surface established that the temporal broadening is a result of a rate-limiting
      kinetic step associated with extrusion of the vesicular contents at the cell
      surface. The data do not support a rate-limiting process due to restricted efflux
      from a small pore. When combined with previous results, the data suggest that the
      rate-limiting step for chemical secretion from adrenal medullary cells during
      exocytosis is the dissociation of catecholamines from the vesicular matrix at the
      surface of the cell.

PMID- 7711265
TI  - Temperature dependence of Ca2+ wave properties in cardiomyocytes: implications
      for the mechanism of autocatalytic Ca2+ release in wave propagation.
AB  - Digital imaging microscopy of fluo-3 fluorescence was used to study the velocity
      and shape of intracellular Ca2+ waves in isolated rat cardiomyocytes as a
      function of temperature. Decreasing the temperature from 37 to 17 degrees C
      reduced the longitudinal wave velocity by a factor of 1.8 and remarkably slowed
      the decay of [Ca2+]i in the trailing flank of a wave. Using image analysis, rise
      times, and half-maximum decay times of local Ca2+ transients, which characterize
      the processes of local Ca2+ release and removal, were determined as a function of
      temperature. Apparent activation energies for wave front propagation, local Ca2+
      release, and local Ca2+ removal were derived from Arrhenius plots and amounted to
      -23, -28, and -46 kJ/mol, respectively. The high activation energy of Ca2+
      removal, which arises from the activity of the sarcoplasmic reticulum (SR) Ca2+
      ATPase, relative to those of longitudinal wave propagation and local Ca2+ release
      excludes the hypothetical mechanism of regenerative "spontaneous Ca2+ release,"
      in which Ca2+ that has been taken up from the approaching wavefront triggers Ca2+
      release at a luminal site of the SR. It is consistent, however, with the
      hypothesis that Ca2+ wave propagation is based on Ca(2+)-induced Ca2+ release
      where Ca2+ triggers release on the cytosolic face of the SR.

PMID- 7711266
TI  - A fractional calculus approach to self-similar protein dynamics.
AB  - Relaxation processes and reaction kinetics of proteins deviate from exponential
      behavior because of their large amount of conformational substrates. The dynamics
      are governed by many time scales and, therefore, the decay of the relaxation
      function or reactant concentration is slower than exponential. Applying the idea
      of self-similar dynamics, we derive a fractal scaling model that results in an
      equation in which the time derivative is replaced by a differentiation (d/dt)beta
      of non-integer order beta. The fractional order differential equation is solved
      by a Mittag-Leffler function. It depends on two parameters, a fundamental time
      scale tau 0 and a fractional order beta that can be interpreted as a self
      similarity dimension of the dynamics. Application of the fractal model to ligand
      rebinding and pressure release measurements of myoglobin is demonstrated, and the
      connection of the model to considerations of energy barrier height distributions
      is shown.

PMID- 7711267
TI  - Normal modes as refinement parameters for the F-actin model.
AB  - The slow normal modes of G-actin were used as structural parameters to refine the
      F-actin model against 8-A resolution x-ray fiber diffraction data. The slowest
      frequency normal modes of G-actin pertain to collective rearrangements of
      domains, motions that are characterized by correlation lengths on the order of
      the resolution of the fiber diffraction data. Using a small number of normal mode
      degrees of freedom (< or = 12) improved the fit to the data significantly. The
      refined model of F-actin shows that the nucleotide binding cleft has narrowed and
      that the DNase I binding loop has twisted to a lower radius, consistent with
      other refinement techniques and electron microscopy data. The methodology of a
      normal mode refinement is described, and the results, as applied to actin, are
      detailed.

PMID- 7711268
TI  - Polymer- and salt-induced toroids of hexagonal DNA.
AB  - A model is proposed for polymer- and salt-induced toroidal condensates of DNA,
      based on a recent theory of the undulation enhancement of the electrostatic
      interaction in the bulk hexagonal phase of semiflexible polyions. In a continuum
      approximation, the thermodynamic potential of a monomolecular toroid may be split
      up in bulk, surface, and curvature contributions. With the help of an approximate
      analytical minimization procedure, the optimal torus dimensions are calculated as
      a function of the concentrations of inert polymer and added salt. The stability
      of the torus is analyzed in terms of its surface tension and a bulk melting
      criterion. The theory should be applicable to psi-toroids that are not too thick.

PMID- 7711269
TI  - Acetylcholinesterase: diffusional encounter rate constants for dumbbell models of
      ligand.
AB  - For some enzymes, virtually every substrate molecule that encounters the entrance
      to the active site proceeds to reaction, at low substrate concentrations. Such
      diffusion-limited enzymes display high apparent bimolecular rate constants
      ((kcat/KM)), which depend strongly upon solvent viscosity. Some experimental
      studies provide evidence that acetylcholinesterase falls into this category.
      Interestingly, the asymmetric charge distribution of acetylcholinesterase,
      apparent from the crystallographic structure, suggests that its electrostatic
      field accelerates the encounter of its cationic substrate, acetylcholine, with
      the entrance to the active site. Here we report simulations of the diffusion of
      substrate in the electrostatic field of acetylcholinesterase. We find that the
      field indeed guides the substrate to the mouth of the active site. The computed
      encounter rate constants depend upon the particular relative geometries of
      substrate and enzyme that are considered to represent successful encounters. With
      loose reaction criteria, the computed rates exceed those measured experimentally,
      but the rate constants vary appropriately with ionic strength. Although more
      restrictive reaction criteria lower the computed rates, they also lead to
      unrealistic variation of the rate constants with ionic strength. That these
      simulations do not agree well with experiment suggests that the simple diffusion
      model is incomplete. Structural fluctuations in the enzyme or events after the
      encounter may well contribute to rate limitation.

PMID- 7711270
TI  - Theoretical study of model compound I complexes of horseradish peroxidase and
      catalase.
AB  - Theoretical studies of the electronic structure and spectra of models for the
      ferric resting state and Compound I intermediates of horseradish peroxidase (HRP
      I) and catalase (CAT-I) have been performed using the INDO-RHF/CI method. The
      goals of these studies were twofold: i) to determine whether the axial ligand of
      HRP is best described as imidazole or imidazolate, and ii) to address the long
      standing question of whether HRP-I and CAT-I are a1u and a2u tau cation radicals.
      Only the imidazolate HRP-I model led to a calculated electronic spectra
      consistent with the experimentally observed significant reduction in the
      intensity of the Soret band compared with the ferric resting state. These results
      provide compelling evidence for significant proton transfer to the conserved Asp
      residue by the proximal histidine. The origin of the observed reduction of the
      Soret band intensity in HRP-I and CAT-I spectra has been examined and found to be
      caused by the mixing of charge transfer transitions into the predominantly
      porphyrin tau-tau transitions. For both HRP-I and CAT-I, the a1u porphyrin tau
      cation state is the lowest energy, and it is further stabilized by both the
      anionic form of the ligand and the porphyrin ring substituents of protoporphyrin
      IX. The calculated values of quadrupole-splitting observed in the Mossbauer
      resonance of HRP-I and CAT-I are similar for the a1u and a2u tau cation radicals.
      Electronic spectrum of the a1u tau cation radical of HRP-I are more similar to
      the observed spectra, whereas the spectra of both a1u tau and a2u tau cation
      radicals of CAT-I resemble the observed spectra. These results also indicate the
      limitations of using any one observable property to try to distinguish between
      these states. Taken together, comparison of calculated and observed properties
      indicate that there is no compelling reason to invoke the higher energy a2u tau
      cation radical as the favored state in HRP-I and CAT-I. Both ground-state
      properties and electronic spectra are consistent with the a1u tau cation radical.

PMID- 7711271
TI  - Modulation of intramolecular interactions in superhelical DNA by curved
      sequences: a Monte Carlo simulation study.
AB  - A Monte Carlo model for the generation of superhelical DNA structures at
      thermodynamic equilibrium (Klenin et al., 1991; Vologodskii et al., 1992) was
      modified to account for the presence of local curvature. Equilibrium ensembles of
      a 2700-bp DNA chain at linking number difference delta Lk = -15 were generated,
      with one or two permanent bends up to 120 degrees inserted at different
      positions. The computed structures were then analyzed with respect to the number
      and positions of the end loops of the interwound superhelix, and the
      intramolecular interaction probability of different segments of the DNA. We find
      that the superhelix structure is strongly organized by permanent bends. A DNA
      segment with a 30 degrees bend already has a significantly higher probability of
      being at the apex of a superhelix than the control, and for a 120 degrees bend
      the majority of DNAs have one end loop at the position of the bend. The entropy
      change due to the localization of a 120 permanent bend in the end loop is
      estimated to be -17 kJ mol-1 K-1. When two bends are inserted, the conformation
      of the superhelix is found to be strongly dependent on their relative positions:
      the straight interwound form dominates when the two bends are separated by 50% of
      the total DNA length, whereas the majority of the superhelices are in a branched
      conformation when the bends are separated by 33%. DNA segments in the vicinity of
      the permanent bend are strongly oriented with respect to each other.

PMID- 7711272
TI  - Inactivation in ShakerB K+ channels: a test for the number of inactivating
      particles on each channel.
AB  - Fast inactivation in ShakerB K channels results from pore-block caused by "ball
      peptides" attached to the inner part of each K channel. We have examined the
      question of how many functional inactivating balls are on each channel and how
      this number affects inactivation and recovery from inactivation. To that purpose
      we expressed ShakerB in the insect cell line Sf9 and gradually removed
      inactivation by perfusing the cell interior with the hydrolytic enzyme papain
      under whole cell patch clamp. Inactivation slows down as the balls are removed by
      an amount consistent with the presence of four balls on each channel. Recovery
      from inactivation has the same time course early and late in papain action; it
      does not depend on the number of balls remaining on the channel, consistent with
      the idea that reinactivation is not significant during recovery from
      inactivation. Our conclusion is that ShakerB has four ball peptides, each capable
      of causing inactivation. Statistically, the balls are identical and independent.
      The stability of N-type inactivation by the remaining balls is not appreciably
      affected by removing some of the balls from a channel.

PMID- 7711274
TI  - Biophysical Society. 39th annual meeting. 12-16 February 1995, San Francisco,
      California. Abstracts.

PMID- 7711273
TI  - Localization and interaction of N-methyl-D-aspartate and non-N-methyl-D-aspartate
      receptors of lamprey spinal neurons.
AB  - Small volumes of N-Methyl-D-Aspartate (NMDA) and non-NMDA excitatory amino acid
      receptor agonists were applied to localized regions of the dendritic trees of
      lamprey spinal neurons along their medial-lateral axis to obtain a spatial map of
      glutamate receptor distribution. Voltage clamp and frequency domain methods were
      used to obtain quantitative kinetic data of the voltage dependent ionic channels
      located both on the soma and on highly branched dendritic membranes. Pressure
      pulses of NMDA applied to the most peripheral regions of the dendritic tree
      elicited large somatic impedance increases, indicating that the most peripheral
      dendrites are well supplied with NMDA receptors. Experiments done with kainate
      did not elicit somatic responses to agonist applications on peripheral dendrites.
      The data obtained are consistent with the hypothesis that the activation of NMDA
      receptors by exogenous glutamate is significantly modified by the simultaneous
      activation of non-NMDA receptors, which shunts the NMDA response. The non-NMDA
      shunting hypothesis was tested by a combined application of kainate and NMDA to
      mimic the action of glutamate showing that the shunting effect of non-NMDA
      receptor activation virtually abolished the marked voltage dependency typical of
      NMDA receptor activation. These data were interpreted with a compartmental
      neuronal model having both NMDA and non-NMDA receptors.

PMID- 7711275
TI  - For-Met-Lys-Phe-For-Met-Lys-Phe-: a new cyclic analogue of the chemotactic
      formylpeptides.
AB  - As a continuation of the studies on chemotactic N-formylpeptides, we report here
      the synthesis and activity of a new cyclic analogue of the prototypical ligand
      For-Met-Leu-Phe-OMe. The new compound For-Met-Lys-Phe-For-Met-Lys-Phe- (4)
      contains a 20-membered cyclic moiety made up of a dimeric -Lys-Phe- sequence in
      which For-Met is attached to each Lys alpha-NH2 and hence remains outside the
      ring. The conformation in the crystal of the cyclic precursor of 4, namely Boc
      Lys-Phe-Boc-Lys-Phe- (2) and the activity of the structurally related linear
      analogue For-Met-Lys(Z)-Phe-OBzl (6), have also been examined. The new analogues
      4 and 6 are active as chemoattractants, secretagogues, and superoxide anion
      generating agents, when tested on human neutrophils. The structure-activity
      relationship is discussed and related to that of a previously studied cyclic
      model.

PMID- 7711276
TI  - Structural modification of DNA by a DNA-binding motif SPKK: detection of changes
      in base-pair hydrogen bonding and base stacking by UV resonance Raman
      spectroscopy.
AB  - Interactions of a DNA-binding motif SPKK with polynucleotides have been
      investigated by uv resonance Raman spectroscopy. Analysis of the Raman spectra
      has shown that the tetrapeptide SPKK weakens the adenine-thymine base-pair
      hydrogen bonding in poly(dA-dT).poly(dA-dT) and reduces the adenine-adenine base
      stacking interactions in poly(dA).poly(dT), both effects being indicative of
      destabilization of the DNA double helical structure. On the other hand, poly(dG
      dC).poly(dG-dC) and poly(dG).poly(dC) do not show any structural change in the
      presence of SPKK. The present observations confirm that the SPKK motif, which is
      frequently found in histone H1 proteins, specifically binds to A/T-rich regions
      of DNA and loosens the DNA double-helical structure. One of the roles of the SPKK
      motifs in histones may be to increase DNA flexibility so that DNA can wrap around
      core histones and be assembled into chromosomes more easily.

PMID- 7711277
TI  - Pressure dependence of the helix-coil transition temperature of poly[d(G-C)].
AB  - The pressure dependence of the helix-coil transition temperature (Tm) of poly[d(G
      C)] was studied as a function of sodium ion concentration in phosphate buffer.
      The molar volume change of the transition (delta V) was calculated using the
      Clapeyron equation and calorimetrically determined enthalpies. The delta V of the
      transition increased from +4.80 (+/- 0.56) to +6.03 (+/- 0.76) mL mol-1 as the
      sodium ion concentration changed from 0.052 to 1.0M. The van't Hoff enthalpy of
      the transition calculated from the half-width of the differentiated transition
      displayed negligible pressure dependence; however, the value of this parameter
      decreased with increasing sodium ion concentration, indicating a decrease in the
      size of the cooperative unit. The volume change of the transition exhibits the
      largest magnitude of any double-stranded DNA polymer measured using this
      technique. For poly[d(G-C)] the magnitude of the change in delta V with sodium
      ion concentration (0.94 +/- 0.05 mL mol-1) is approximately one-half that
      observed for either poly[d(A-T)] or poly(dA).poly(dT). The delta V values are
      interpreted as arising from changes in the hydration of the polymer due to the
      release of counterions and changes in the stacking of the bases of the coil form.
      As a consequence of solvent electrostriction, the release of counterions makes a
      net negative contribution to the total delta V, implying that disruption of the
      stacking interactions contributes a positive volume change to the total delta
      V.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711278
TI  - The osmotic sensitivity of netropsin analogue binding to DNA.
AB  - The binding of a netropsin analogue to random sequence DNA, monitored by CD, is
      seen dependent on the concentration of neutral solutes. The binding free energy
      decreases linearly with solute osmolal concentration and the magnitude of the
      effect is insensitive to the chemical identity of the solute for betaine,
      sorbitol, and triethylene glycol. These solutes appear to modulate binding
      through their effect on water activity and changes in the hydration of the drug
      and DNA in the complex reaction, not through a direct interaction with the
      reactants or the product. The dependence of binding constant on solute
      concentration can be interpreted as an additional binding of some 50-60 extra
      solute excluding water molecules by the complex. A water sensitivity of drug
      binding is further seen from the dependence of binding constants on the type of
      anion in solution. Anions in the Hofmeister series strongly affect bulk water
      free energies and entropies. The differences in netropsin analogue binding to DNA
      with Cl-, F-, and ClO4- are consistent with the effect observed with neutral
      solutes. The ability to measure changes in water binding associated with a
      specific DNA interaction is a first step toward correlating changes in hydration
      with the strength and specificity of binding.

PMID- 7711279
TI  - The influence of pregnancy on the biotransformation and urinary excretion of
      methoxyphenamine in mice.
AB  - (i) The urinary elimination of methoxyphenamine (MPA) and its metabolites in
      underivatized samples was examined after single and multiple oral administration
      to pregnant and non-pregnant mice by GLC and GLC-MS. (ii) The major metabolite O
      desmethylmethoxyphenamine (ODMP), along with lesser amounts of N
      desmethylmethoxyphenamine (NDMP) and 2-hydroxyamphetamine (2OH), were the only
      metabolites detected in urine extracts of pregnant and non-pregnant mice. 5
      Hydroxymethoxyphenamine (5HMP) was not detected. Enzyme hydrolysis did not
      increase the recovery of either substrate or metabolites in either the pregnant
      or non-pregnant animals. The results show that MPA metabolism in the Swiss
      Webster mouse is distinctly different from that seen in man and other laboratory
      animals. (iii) The mean MPA:ODMP ratio in day-6 urine from pregnant mice after a
      single dose was 0.31 +/- 0.04. The NDMP:ODMP ratios were less than 0.10 in all
      samples. Non-pregnant mice urine had equivalent amounts of MPA, NDMP, ODMP, and
      2OH after multiple dosing. (iv) While multiple dosing and pregnancy did not alter
      either the urinary recovery or profile of the metabolites detected, there was a
      linear decrease in the MPA:ODMP ratio during gestation. (v) MPA was extensively
      metabolized to ODMP in the male mice, and the MPA:ODMP ratio of 0.41 was slightly
      higher than that observed in the pregnant and non-pregnant females.

PMID- 7711280
TI  - The relationship between pharmacokinetic behaviour of glycyrrhizin and hepatic
      function in patients with acute hepatitis and liver cirrhosis.
AB  - The pharmacokinetic behavior of glycyrrhizin in four patients with acute
      hepatitis (hepatitis group) and six patients with liver cirrhosis (cirrhosis
      group) receiving chronically an IV administration of a 120 mg dose once a day or
      once every other day of glycyrrhizin was investigated. The plasma concentration
      of glycyrrhizin declined monoexponentially in both groups. The elimination half
      life (t1/2) for glycyrrhizin in the hepatitis and cirrhosis groups varied
      significantly in the range of 2.7-7.6 h and 6.2-40.1 h, and the total body
      clearance (CLtot) in the range of 2.8-23.2 mL h-1 kg-1 and 1.4-12.9 mL h-1 kg-1,
      respectively. The t1/2 for glycyrrhizin in the hepatitis and the cirrhosis groups
      was about twice and eight times that in normal subjects, respectively, as
      reported previously, and CLtot values were about 0.7 and 0.23 times that in
      normal subjects, respectively. There was significant correlation between the
      CLtot and hepatic function (aspartate aminotransferase and alanine
      aminotransferase in serum) in both patient groups. With improvement of the liver
      function, the CLtot for glycyrrhizin increased from 2.8 ml h-1 kg-1 to 11.4 mL h
      1 kg-1, and the t1/2 shortened from 7.6 h to 3.4 h. These findings indicated that
      the variation of pharmacokinetic behaviour of glycyrrhizin in both groups was
      closely related to the extent of the liver function.

PMID- 7711281
TI  - An in vitro study of the influence of a drug's molecular weight on its overall
      (Clt), diffusive (Cld) and convective (Clc) clearance through dialysers.
AB  - The dialyser clearance of a drug is the sum of two components: one diffusive,
      arising from the concentration gradient across the membrane, and the other
      convective, arising from the ultrafiltration of plasma water, produced by the
      increases in hydraulic pressure that the membrane undergoes. To demonstrate the
      importance of these clearances during haemodialysis, this study analyses the
      influence of a drug's molecular weight on them. To this end, an experimental
      study of dialysis in vitro was carried out to determine the clearances, in
      aqueous solution, of five drugs of increasing molecular weights (theophylline,
      quinidine, tobramycin, digoxin, and vancomycin), using two series of dialysers
      with the same type of membrane (Cuprophan), differing in effective surface area
      and ultrafiltration coefficient. From the data obtained in this study, the
      importance of quantifying convective clearance during haemodialysis becomes
      apparent since if it is not taken into account errors of up to 20% and more may
      be made. This is particularly so if the drug is of high molecular weight and if a
      high filtration rate is being used.

PMID- 7711282
TI  - An evaluation of numerical integration algorithms for the estimation of the area
      under the curve (AUC) in pharmacokinetic studies.
AB  - Six numerical integration algorithms based on linear and log trapezoidal methods
      as well as four cubic-spline methods were proposed for estimation of area under
      the curve (AUC). These six different algorithms were implemented using IMSL/IDL
      command language and evaluated using data simulated under five different dosing
      conditions and two different sampling conditions. Comparisons between AUC
      estimations using these six different algorithms and the theoretical results were
      made in terms of both overall AUC values and the superimposability of the
      concentration-time profiles. In well designed studies with ample data points, the
      algorithm based on IMSL/IDL function CSSHAPE with concavity preservation gave the
      best performance. In contrast, when the frequency of blood collection was
      limited, the algorithm based on the log trapezoidal rule proved to be stable with
      reasonable accuracy, and is recommended as the practical method for numerical
      interpolation and integration in pharmacokinetic studies. Algorithms based on the
      combination of the log trapezoidal rule and cubic-spline methods using IMSL/IDL
      function CSSHAPE can be developed to enhance overall performance.

PMID- 7711283
TI  - The estimation of the plasma free fraction of cyclosporine in rabbits and heart
      transplant patients: the application of a physiological model of renal clearance.
AB  - We estimated the free fraction (fu) of cyclosporine (CyA) in the plasma from
      concentrations of CyA in urine (Cu) and plasma (Cp), urine flow rate (UF), and
      glomerular filtration rate in rabbits and in heart transplant patients. Following
      intravenous administration of CyA (5-30 mg kg-1) in ten NZW rabbits and oral
      administration of CyA (4.8-12.1 mg kg-1) in nine heart transplant patients, CyA
      concentrations in urine and plasma were measured by HPLC. The ratios of Cu to Cp
      and UF data were fitted to a physiological model of renal clearance using NONMEM.
      The free fraction of cyclosporine in the rabbits and the heart transplant
      patients was 0.0122 and 0.14, respectively. Because of the relatively low
      permeability of CyA across the tubular epithelium, no apparent equilibrium
      between Cu and Cp at any urine flow rate was reached and, therefore, the Cu to Cp
      ratio will not be equal to fu.

PMID- 7711284
TI  - The validation of the intestinal permeability approach to predict oral fraction
      of dose absorbed in humans and rats.

PMID- 7711285
TI  - 1001 protein kinases redux--towards 2000.
AB  - Recent genomic analysis indicates that the number of protein kinase genes in
      eukaryotes may be higher than previously thought, and vertebrate genomes may
      contain in the vicinity of 2000. In addition to the growing protein
      serine/protein-tyrosine kinase superfamily, new types of protein kinase have been
      discovered that operate on different structural principles. The structures of
      four protein-serine kinases have been solved and have revealed a common
      structural core containing the highly conserved residues in the catalytic domain.
      These structures provide insights into substrate selectivity and protein kinase
      activation. New regulatory principles for protein kinase have been uncovered,
      including phosphorylation of residues within the catalytic domain by a second
      protein kinase, new second messengers and specific protein inhibitors. Evidence
      that protein kinase cascades play an important role in signal transduction has
      emerged. A number of fundamental cellular processes such as the cell cycle and
      transcription have been shown to require protein phosphorylation.

PMID- 7711286
TI  - Membrane-associated tyrosine kinases as molecular switches.
AB  - Tyrosine kinases can be associated with membranes as membrane-spanning integral
      membrane proteins or as intracellular peripheral membrane proteins. Both
      categories of tyrosine kinase transduce extracellular signals to the cytosol by
      switching between inactive and active states. Switching is achieved by changes in
      phosphorylation state and intra- and inter-molecular binding interactions. In
      turn, activated tyrosine kinases affect their substrates by changing their
      phosphorylation state and by binding them.

PMID- 7711287
TI  - Signal transduction via serine/threonine kinase receptors.
AB  - A number of serine/threonine kinase receptors have recently been identified. Most
      of the members of this family are type I or type II receptors for proteins in the
      transforming growth factor-beta (TGF-beta) superfamily. The type I and type II
      receptors form heteromeric receptor complexes after binding of the ligands, and
      transduce intracellular signals. TGF-beta type I receptor needs type II receptor
      for ligand binding, and type II receptor needs type I receptor for signalling.
      The signal transducing molecules that interact with heteromeric serine/threonine
      kinase receptor complexes remain to be elucidated; cyclin-dependent kinases and
      the retinoblastoma protein appear to be downstream elements in the
      antiproliferative pathway of TGF-beta.

PMID- 7711288
TI  - Protein kinases and cell cycle control.
AB  - Protein kinases play a central role in the regulation of the eukaryotic cell
      cycle. Recent research has concentrated on a particular family of protein
      kinases, the cyclin-dependent kinases (CDKs), and their involvement in regulating
      particular cell cycle transitions, such as the initiation of DNA synthesis (S
      phase) or of cell division (mitosis). One can think of these enzymes as the basic
      machinery of the cell cycle; their activity is then modulated by proteins which
      transduce signals from the external environment, and by proteins that monitor the
      progress of events such as DNA replication or the formation of the mitotic
      spindle. This review will be structured so as to introduce the cyclin-CDK motif,
      outline which cyclin-CDKs are involved at different cell cycle stages, their
      direct regulation by other protein kinases and phosphatases, and lastly the
      importance of other protein kinases in the cell cycle.

PMID- 7711289
TI  - Roles of the Snf1/Rkin1/AMP-activated protein kinase family in the response to
      environmental and nutritional stress.
AB  - The AMP-activated protein kinase (AMPK) inhibits several biosynthetic pathways in
      mammals, and is activated in response to stresses which cause ATP depletion, e.g.
      heat shock. This system may therefore protect cells against environmental stress
      by switching off biosynthesis (i.e. growth) to conserve ATP. Recent biochemical
      and molecular genetic studies have shown that AMPK is closely related to the SNF1
      gene product from Saccharomyces cerevisiae, and its homologues in higher plants.
      SNF1 is required for the response to starvation for glucose. Thus the novel
      function of providing protection against environmental stress may have evolved
      from a more ancient response to nutritional stress.

PMID- 7711290
TI  - The eIF-2 alpha kinases: regulators of protein synthesis in starvation and
      stress.
AB  - Phosphorylation of translation initiation factor 2 alpha is a highly conserved
      mechanism for down-regulating protein synthesis in response to starvation or
      stress. The yeast eIF-2 alpha kinase GCN2 is stimulated by deprivation for amino
      acids or purines. In addition to inhibiting general protein synthesis, GCN2
      specifically stimulates translation of GCN4, a transcriptional activator of amino
      acid biosynthetic genes. HRI is an eIF-2 alpha kinase that is activated in rabbit
      reticulocytes by heme-deprivation and stress conditions that elicit the heat
      shock response. The eIF-2 alpha kinase DAI is activated by double-stranded RNA
      during viral infections and is an important component of the interferon response.
      DAI has also been implicated as a tumor suppressor. These protein kinases provide
      an important means of coupling the rate of protein synthesis and cell division to
      environmental conditions.

PMID- 7711291
TI  - Protein kinases and the response to DNA damage.
AB  - Exposure of eukaryotic cells to DNA damaging agents induces gene expression and
      inhibits cell cycle progression. The first response to damage that has been
      measured is an increase in protein kinase activity. Several protein kinases are
      activated in cells exposed to DNA damaging agents, and other kinases that correct
      damage hypersensitivity mutants have been identified genetically. Current
      challenges include determining which responses result from damage to DNA and
      identifying the immediate detectors of damaged DNA that initiate signal
      transduction.

PMID- 7711292
TI  - Use of the piglet to study the role of growth factors in neonatal intestinal
      development.
AB  - Milk growth factors are thought to contribute to postnatal gastrointestinal
      growth. The roles of epidermal growth factor (EGF) and insulin-like growth factor
      I (IGF-I) in the neonatal piglet intestine were investigated. In the first study,
      piglets were infected with rotavirus on d 4 postpartum and received formula
      containing 0, 500 or 1000 micrograms/l of EGF for 8 days. A non-infected control
      group received no EGF. Infected piglets developed severe diarrhea and gained 60%
      less weight than controls. Rotaviral infection caused a 37% decrease in villus
      height and 40% decreases in intestinal enzyme activities compared to control.
      Oral EGF increased villus height and lactase activity in a linear dose-response
      fashion. Our results suggest that supplementation of formulas with high
      physiological levels of EGF may aid in small intestinal recovery. A second study
      investigated absorption of orally administered IGF-I. Newborn piglets were fitted
      with catheters via the umbilical artery and vein. Piglets were given formula
      containing 25 microCi of [125I]-IGF-I and blood samples were drawn for 24O min.
      Total radioactivity, protein bound counts, and counts immunoprecipitable with an
      antibody to IGF-I were determined in plasma. Radioactivity was detected in portal
      and arterial plasma within 15 min and rose throughout the study, however, protein
      bound counts were stable at 20-30% of total counts between 30 and 180 min
      postgavage. Approximately 10% of the counts were immunoprecipitable by a
      polyclonal antibody to IGF-I, suggesting that up to 10% of orally administered
      IGF-I may be absorbed intact.

PMID- 7711293
TI  - Studies on the physiological role of ANF in ACTH regulation.
AB  - To investigate the impact of changes in the level of the endogenous atrial
      natriuretic factor (ANF) on pituitary-adrenocortical activity, the secretion of
      corticotropin (ACTH) and corticosterone was studied under the conditions of
      enhanced and decreased circulating ANF levels in rats. Volume expansion
      (intravenous infusion of 5 ml of saline within 2 min) induced significant
      elevation in ANF levels 5 min after the infusion, whereas ACTH levels remained
      unchanged during the first 20 min and were elevated only at 40 min, i.e. at the
      time when ANF levels were again normal. Water deprivation for 48 h resulted in
      decreased ANF levels and increased corticosterone concentrations. ANF
      concentrations in peripheral blood obtained under thiopental anesthesia were
      lower than those in blood sampled in the same rats in conscious state. However,
      such changes were not observed in water deprived animals. In addition, ANF was
      found to be present in the hypophysial portal blood of anesthetized rats. In
      conscious sheep, portal ANF levels were significantly higher than those in
      peripheral blood. Our results support the suggestion of an inhibitory role of ANF
      in the control of ACTH release and indicate that this role of ANF is
      physiologically relevant.

PMID- 7711294
TI  - Effect of ovariectomy on the binding characteristics of hypothalamic mu opioid
      receptors in the rat.
AB  - The present experiments have been performed to analyze whether ovariectomy,
      performed in adult female rats, might influence the binding characteristics of
      hypothalamic mu binding sites. To this purpose, different groups of
      ovariectomized females have been killed by decapitation 1, 3, 7, 15 and 21 days
      after surgery, and the binding characteristics (Bmax and Kd) of the mu receptors
      have been determined in their hypothalami. Dihydromorphine was used as a specific
      mu ligand. The data obtained have been compared with those derived from the
      hypothalami of adult female rats in the morning of proestrus, when the density of
      hypothalamic mu opioid receptors reaches its highest concentration. Blood from
      trunk vessels was also collected for the evaluation of serum LH levels by
      radioimmunoassay. The results obtained have shown that one day after ovariectomy,
      the number of hypothalamic mu opioid binding sites is as high as that found in
      proestrus animals. The number of these binding sites tends to decrease on days 3,
      7 and 15 after surgery. On day 21 after gonadectomy, the number of mu binding
      sites results to be significantly lower than that observed in the hypothalami of
      intact female rats in the morning of proestrus and in the hypothalami of female
      animals castrated since one day. The value of the Kd did not show any variation
      on days 1, 3, 15 and 21; however, a significant increase of this parameter (which
      indicates a decrease of the affinity of the ligand for its receptors) was
      observed on day 7 after ovariectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711295
TI  - Effect of 3,5,3'-L-triiodothyronine on hepatic ornithine decarboxylase and
      thymidine kinase activity in rat after partial hepatectomy.
AB  - Partial hepatectomy (60%) led to the biphasic increase (first one at 4 h and
      second one at 48 h) of ornithine decarboxylase activity in the remnant rat liver.
      Daily administration of 3,5,3'-L-triiodothyronine (T3) (10 micrograms/100 g) to
      rats for 7 days before partial hepatectomy had little effect on the enzyme
      activity. At five days, ornithine decarboxylase activity declined to control
      level (sham operated controls) and its activity was significantly enhanced by T3.
      Ornithine decarboxylase gene expression in the rat liver (examined by Northern
      blot analysis using poly A+ mRNA) started to increase 4 h after partial
      hepatectomy, remained elevated for 48 h and decreased after 5 days. Its activity
      was not altered by T3 treatment. The activity of thymidine kinase increased
      progressively after partial hepatectomy, but its peak value was delayed by T3
      administration. Plasma prolactin levels increased within 5-15 min after liver
      resection, then declined to control values and increased 24 h after the surgery.
      The data demonstrate that the changes in ornithine decarboxylase activity in the
      rat liver after partial hepatectomy might result from the direct effect of
      prolactin on the activity of enzyme rather than from its induction by hormone.
      Triiodothyronine administration altered both ornithine decarboxylase and
      thymidine kinase activities suggesting that T3 appears to regulate ornithine
      decarboxylase activity at post-translational level.

PMID- 7711296
TI  - Dietary fish oil and olive oil improve the liver insulin receptor tyrosine kinase
      activity in high sucrose fed rats.
AB  - In order to shed light on the possible beneficial effect of dietary unsaturated
      fatty acids on insulin binding, the effect of fish oil and olive oil
      administration on insulin binding, autophosphorylation and tyrosine kinase
      activity of partially purified liver insulin receptors were investigated. These
      data were confronted with the parameters of sugar and lipid metabolism (blood
      glucose, insulin and triglycerides), with liver plasma membrane fluidity and
      fatty acid composition. High sucrose feeding resulted in the elevation of blood
      glucose and triglyceride level, while the supplementation of animals with fish
      oil reduced that of triglycerides and olive oil that of insulin. Any significant
      changes between experimental groups were not detected either in insulin binding
      to partially purified liver insulin receptor nor in receptor autophosphorylation.
      However, the insulin stimulated tyrosine kinase activity towards an exogenous
      substrate (poly(Glu,Tyr)) was decreased by about 50% in the receptors solubilized
      from liver membranes of sucrose fed rats. Increased dietary intake of fish oil or
      olive oil restored the activity of insulin tyrosine kinase towards control
      values, half maximal effect being obtained at similar insulin concentration in
      all groups. Such improvement might be due to the induced increase of membrane
      fluidity by unsaturated fatty acids, and/or to the decrease of insulinemia.

PMID- 7711298
TI  - Changes of calcemia and magnesemia during oral glucose tolerance test (OGTT) in
      relation to glucose tolerance.
AB  - We have examined 56 subjects with normal glucose tolerance (NGT), 33 with
      impaired glucose tolerance (IGT) and 15 diabetics type II (DM) by an oral glucose
      tolerance test with 75 g of glucose and in addition to glycemia and C-peptide we
      estimated also calcemia, magnesemia, ionized calcium level (plus corrected
      ionized calcium level) in all time intervals. The basal glycemia and C-peptide
      values were different in each examined group, while the magnesium values
      distinguished only the DM group from the others. The corrected Ca2+ in 60 min
      decreased significantly in DM, while after 120 min there were no differences in
      the values. Magnesemia in NGT decreased after 60 and 120 min, while by IGT and DM
      it rised in both such intervals. The difference between IGT and DM was highly
      significant. Our findings give evidence about the changes in the distribution of
      magnesium already at an early stage of decrease glucose tolerance. The importance
      of this finding for an early IGT diagnostics and its further classification still
      remains to be definitely evaluated.

PMID- 7711297
TI  - The activity of thymidine kinase in homogenates of rat thyroid lobes incubated in
      vitro in the presence of vasoactive intestinal polypeptide; interactions with
      atropine and carbachol.
AB  - We examined the effect of vasoactive intestinal polypeptide (VIP) on thymidine
      kinase (TK) activity in the tissue of rat thyroid lobes incubated in vitro.
      Additionally, thyrotropin, epidermal growth factor, as well as atropine and
      carbachol were studied. It was shown that: 1. thyrotropin and epidermal growth
      factor did not essentially affect TK activity; 2. the effect of VIP was dose
      dependent: the high concentrations of peptide (10(-7) M and 10(-5) M) suppressed,
      while the lower concentrations (10(-15)M, 10(-13)M, 10(-11)M and 10(-9) M)
      enhanced TK activity; 3. atropine tended to increase TK activity, however, that
      rise did not attain statistical significance; 4. VIP, when used together with
      atropine, decreased TK activity when compared with the activity in question after
      exposure to atropine alone; 5. carbachol suppressed TK activity; 6. the joint
      action of carbachol and VIP did not significantly change the activity of the
      examined enzyme.

PMID- 7711299
TI  - HMG-CoA reductase activity in the liver of rats with hereditary
      hypertriglyceridemia: effect of dietary fish oil.
AB  - To assess the possible participation of liver microsomal 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase in the hypocholesterolemic effect
      of fish oil (FO) in rats with hereditary hypertriglyceridemia (derived from the
      Wistar strain, obtained from VELAZ, Prague, Czech Rep.), male animals were fed a
      basal diet (BD) or a high sucrose diet (SD-63 cal %) with or without FO
      supplement (30 wt% n-3 polyunsaturated fatty acids) for 21 days. The feeding with
      high sucrose diet resulted in increased HMG-CoA reductase activity; (P < 0.05).
      However, FO added to the diet suppressed this stimulated enzymatic activity
      (919.05 +/- 76.86 vs. 614.05 +/- 48.53 pmol/min/mg prot.; P < 0.05) and decreased
      cholesterol (CH) content in both serum and the liver of HTG rats fed basal as
      well as sucrose diet; (P < 0.05). The results of the study demonstrated that the
      hypocholesterolemic effect of FO added to the diet was mediated under certain
      conditions, by affecting of HMG-CoA reductase activity and not only by its effect
      on specific receptors as demonstrated before.

PMID- 7711300
TI  - In vitro bioassay for hypertrehalosemic hormone-dependent trehalose biosynthesis
      by fat body from adult Blaberus discoidalis cockroaches.
AB  - An in vitro bioassay suitable for routine use to investigate hypertrehalosemic
      hormone (HTH)-dependent trehalose biosynthesis was developed for the cockroach
      fat body. Blaberus discoidalis fat bodies were isolated and divided so that eight
      matched pieces from a single tissue could be compared for multiple control and
      experimental treatments. Optimum incubation conditions and the properties of HTH
      dependent trehalose synthesis were determined. Dose-response studies determined
      an EC50 of 0.044 nM. HTH for male fat body and 0.16 nM HTH for female tissue. HTH
      increased trehalose production by male fat body 3-fold compared to only a 67%
      maximum increase by the female tissue, and only the male tissue was used in
      subsequent studies. Fat body required only 5-min exposure to HTH for maximum
      trehalose production for 1 h. Trehalose synthesis was inhibited by > or = 15 mM
      trehalose in the incubation medium. The fat body showed a developmental increase
      in trehalose synthesis in vitro that was reflected by hemolymph trehalose in
      vivo. Basal and HTH-related trehalose synthesis were low between days 0 and 10,
      increased 3-fold by day 20, and were high thereafter. These studies have
      established baseline data for future investigations to identify the signal
      transduction mechanisms involved in HTH regulation of fat body metabolism.

PMID- 7711301
TI  - Fate of a terminal olefin with Drosophila microsomes and its inhibitory effects
      on some P-450 dependent activities.
AB  - In vitro bioassays were used to analyze the metabolism of the 11-dodecenoic acid
      (11-DDNA) by microsomes prepared from Drosophila melanogaster RalDDTR strain. 11
      DDNA is metabolized to 11,12-epoxylauric acid (epoxyLA) in a NADPH-dependent way.
      The microsomal production of epoxyLA reaches a plateau very quickly, suggesting
      the occurrence of an enzyme inactivation process. After incubation of microsomes
      with (1-14C)11-DDNA, three proteins of Mr approximately 50 kDa were labeled. 11
      DDNA inhibits the microsomal metabolism of lauric acid and 7-ethoxycoumarin in a
      time and NADPH-dependent process. An inhibition of metabolites generated from DDT
      and testosterone was also obtained but at higher concentrations. These results
      are discussed according to the fact that RalDDTR is an insecticide resistant
      strain characterized as a high metabolizer of the insecticide DDT and also of
      lauric acid, testosterone, and ethoxycoumarin.

PMID- 7711302
TI  - Separation of multiple forms of acidic glutathione S-transferase isozymes in a
      susceptible and a resistant strain of house fly, Musca domestica (L.).
AB  - The acidic glutathione S-transferases from a CSMA (susceptible) strain and a
      Cornell-R (resistant) strain of houseflies were purified and separated utilizing
      affinity chromatography followed by chromatofocusing. Nine fractions were
      isolated from each house fly strain. Fraction 1 had the highest 1-chloro-2,4
      dinitrobenzene vs. 1,2-dichloro-4-nitrobenzene ratio (CDNB/DCNB ratio) in both
      strains and the ratio of all the other fractions tended to decrease as the
      isoelectrical points decreased except for fractions 4 and 9. Most fractions from
      the CSMA strain had higher CDNB conjugation activities than the fractions from
      the Cornell-R strain, but all the fractions from the CSMA strain had lower DCNB
      conjugation activities than fractions from the Cornell-R strain. Steady-state
      kinetics of all the fractions were examined. The Km values obtained from both
      strains ranged from 0.36 to 1.12 mM, while the Vmax value ranged from 3.0 to 32.6
      mumol/min/mg. In the 100,000 g supernatant, the CDNB specific activities in the
      CSMA strain was about 1/3 of the activity in the Cornell-R strain but it was
      about 1.5-fold following affinity chromatography. The specific activity for DCNB
      measured in the CSMA strain was only 1/5 of the activities of the Cornell-R
      strain in the 100,000 g supernatant, but was about the same after affinity
      chromatography. The difference was due to the selectivity of the affinity column
      used in the current study.

PMID- 7711303
TI  - [Fleas and methods of control].
AB  - Over 2,000 species of fleas parasitize mammals and birds. A simplified study of
      their morphology indicates for the main identification criteria. After listing
      the main families of fleas, the author outlines the identification of species
      most often encountered by veterinarians. Knowledge of the different types of flea
      parasitism and their life cycles is essential for effective control measures.
      Control is justified by the direct and indirect pathogenic roles of fleas
      (transmission of plague, tularaemia, myxomatosis, Dipylidium caninum). Effective
      agents are organochlorine compounds, organophosphorus compounds, pyrethroids and
      insect growth regulators, available in various formulations to destroy parasitic
      fleas on animals or in the environment. A novel method is to administer a
      systemic growth regulator to dogs and cats, which persists in the bloodstream and
      inhibits the reproduction of fleas which feed on a treated animal. Advantages and
      disadvantages of each formulation are presented.

PMID- 7711304
TI  - [Lice and methods of control].
AB  - The morphology and biology of sucking lice (Anoplura) and biting lice
      (Mallophaga) are described. A table shows the main species for given hosts and
      provides simplified keys for identification. Lice have a direct pathogenic effect
      (damage to skin and cutaneous appendages, fall in productivity) and an indirect
      effect (transmission of Rickettsia prowazeki, R. quintana and Borrelia
      recurrentis in human beings; African and classical swine fever virus, equine
      infectious anaemia virus and Dipylidium caninum in animals). Control methods,
      current active insecticides (and those being tested) and appropriate formulations
      are outlined.

PMID- 7711305
TI  - [Myiases of economic importance].
AB  - A simplified list of the principal Diptera capable of causing myiasis is followed
      by a brief presentation of the biology, lesions inflicted, and methods of
      treatment and control of the myiases of economic importance. Cochliomyiasis
      caused by Cochliomyia hominivorax is of greatest interest, in view of the damage
      and losses caused by this disease. A brief account of the outbreak of infestation
      in Libya illustrates the danger of this parasite. Other important traumatic
      myiases are described: that due to Chrysomya bezziana, which causes an African
      myiasis similar to cochliomyiasis, and those due to Lucilia cuprina and related
      species. Hypodermyiasis (warble fly infestation) and oestrosis (nasal bot fly
      infestation in sheep) still cause major economic losses in domestic animals,
      justifying their inclusion in control campaigns. The same applies to stomach bot
      flies of the family Gasterophilidae. The account of each myiasis includes notes
      on parasiticides which have been found to be effective. Given the rapidity with
      which a parasite can now be transported from one continent to another, it is
      important for Veterinary Services to be well-informed and vigilant.

PMID- 7711306
TI  - Tsetse flies and their control.
AB  - The authors use a quantitative modelling framework to describe and explore the
      features of the biology of tsetse flies (Glossina spp.) which are important in
      determining the rate of transmission of the African trypanosomiases between
      hosts. Examples are presented of the contribution of previous research on tsetse
      to quantified epidemiological and epizootiological understanding, and areas of
      current ignorance are identified for future study. Spatial and temporal
      variations in risk are important (but rarely-studied) determinants of the impact
      of trypanosomiasis on humans, domestic animals and agricultural activities.
      Recent grid-based sampling surveys to Togo provide valuable data sets on tsetse,
      cattle and trypanosomiasis throughout the country. A combination of ground-based
      meterological and remotely-sensed satellite data, within linear discriminant
      analytical models, enables description of the observed distributions of the five
      species of tsetse occurring in Togo, with accuracies of between 72% (Glossina
      palpalis and G. tachinoides) and 98% (G. fusca). Abundance classes of the two
      most widespread species, G. palpalis and G. tachinoides, are described with
      accuracies of between 47% and 83%. This is especially remarkable given the
      relatively small differences between the average values of the predictor
      variables in areas of differing fly abundance. Similar analyses could be used to
      predict the occurrence and abundance of flies in other areas, which have not been
      surveyed to date, in order to plan tsetse control campaigns or explore
      development options. Finally, some recent tsetse control campaigns are briefly
      reviewed. The shift of emphasis from fly eradication to fly control is associated
      with a devolution of responsibility for control activities from central
      government to local areas, communities or even individuals. The future role of
      central governments will remain crucial, however, in determining the areas in
      which different control options are practised, in facilitating control by local
      communities and in protecting controlled areas from re-invasion by flies from
      other areas.

PMID- 7711307
TI  - Biology and control of tabanids, stable flies and horn flies.
AB  - Tabanids are among the most free-living adult flies which play a role as
      livestock pests. A single blood meal is used as a source of energy for egg
      production (100-1,000 eggs per meal), and females of certain species can oviposit
      before a blood meal is obtained (autogeny). Therefore, the maintenance of annual
      populations requires successful oviposition by only 2% of females. Wild animal
      blood sources are usually available to maintain annual tabanid populations.
      Larval habitats are also independent of domestic livestock. Thus, the use of
      repellents or partial repellents is the only effective chemical strategy to
      reduce the incidence of tabanids on livestock. Permanent traps (and possibly
      treated silhouette traps) can be employed to intercept flies. Selective grazing
      or confinement can also reduce the impact of tabanids. Stable fly adults are
      dependent on vertebrate blood for survival and reproduction, but the amount of
      time spent in contact with the host is relatively small. Stable fly larvae
      develop in manure, spilled feed and decaying vegetation. Management of larval
      habitats by sanitation is the key to stable fly control. Treatment of animals
      with residual insecticides can aid in control; thorough application to the lower
      body parts of livestock is important. Proper use of modified traps, using either
      treated targets or solar-powered electrocution grids, can be effective in
      reducing stable fly populations. Adult horn flies spend the major part of their
      time on the host, and the larvae are confined to bovid manure. Therefore, almost
      any form of topical insecticide application for livestock is effective against
      horn flies, in the absence of insecticide resistance. Treatments should be
      applied when economic benefit is possible; economic gains are associated with
      increased weaning weights and weight gains of yearling and growing cattle. Oral
      chemical treatments (insect growth regulators or insecticides) administered at
      appropriate rates via bolus, water, food or mineral mixtures can inhibit horn fly
      larval development. However, adult horn fly movement among cattle herds limits
      the use of larval control for horn fly population management. The augmentation of
      native parasites, predators and competitors has been attempted and even promoted
      for horn fly and stable fly control, but evidence for the success of such
      programmes is equivocal.

PMID- 7711308
TI  - Non-biting Muscidae and control methods.
AB  - Many non-biting muscids (filth flies) are characterised by the habit of visiting
      manure or rotting organic material to feed and/or oviposit. As these flies also
      often have close associations with human beings, as well as human habitations and
      domestic animals, they are potentially both a nuisance and a contributory factor
      in the transmission of diseases. The authors examine the biology, economic
      importance and control of four of the most important non-biting muscids:
      housefly, Musca domestica; face fly, Musca autumnalis; Australian bush fly, Musca
      vetustissima; sheep head fly, Hydrotaea irritans.

PMID- 7711309
TI  - Nematocera (Ceratopogonidae, Psychodidae, Simuliidae and Culicidae) and control
      methods.
AB  - The biology, veterinary importance and control of certain Nematocera are
      described and discussed. Culicoides spp. (family Ceratopogonidae) transmit the
      arboviruses of bluetongue (BT), African horse sickness (AHS), bovine ephemeral
      fever (BEF) and Akabane. Some other arboviruses have been isolated from these
      species, while fowl pox has been transmitted experimentally by Culicoides. These
      insects are vectors of the parasitic protozoans Leucocytozoon caulleryi and
      Haemoproteus nettionis, and the parasitic nematodes Onchocerca gutturosa, O.
      gibsoni and O. cervicalis. They also cause recurrent summer hypersensitivity in
      horses, ponies, donkeys, cattle and sheep. Farm animals can die as a result of
      mass attack by Simulium spp., which are also vectors of Leucocytozoon simondi, L.
      smithi and the filariae O. gutturosa, O. linealis and O. ochengi. Venezuelan
      equine encephalomyelitis (VEE) and Rift Valley fever (RVF) have been isolated
      from simuliids, and vesicular stomatitis virus New Jersey strain has been
      replicated in Simulium vittatum. Simuliids are well known as vectors of O.
      volvulus, the cause of human onchocercosis (river blindness). The family
      Psychodidae includes the genera Phlebotomus and Lutzomyia (subfamily
      Phlebotominae), vectors of Leishmania spp. in humans, dogs and other mammals.
      Vesicular stomatitis virus Indiana strain has been regularly isolated from
      phlebotomine sandflies. Mass attack by mosquitoes can also prove fatal to farm
      animals. Mosquitoes are vectors of the viruses of Akabane, BEF, RVF, Japanese
      encephalitis, VEE, western equine encephalomyelitis, eastern equine
      encephalomyelitis and west Nile meningoencephalitis, secondary vectors of AHS and
      suspected vectors of Israel turkey meningoencephalitis. The viruses of hog
      cholera, fowl pox and reticuloendotheliosis, the rickettsiae Eperythrozoon ovis
      and E. suis, and the bacterium Borrelia anserina are mechanically transmitted by
      mosquitoes. These insects also induce allergic dermatitis in horses. They
      transmit several filarial worms of both animals and humans, and are of great
      medical importance as vectors of major human diseases, including malaria, yellow
      fever, dengue fever and many more diseases caused by arboviruses.

PMID- 7711310
TI  - Ticks and control methods.
AB  - Ticks are the most important ectoparasites of livestock in tropical and sub
      tropical areas, and are responsible for severe economic losses both through the
      direct effects of blood sucking and indirectly as vectors of pathogens and
      toxins. Feeding by large numbers of ticks causes reduction in live weight gain
      and anaemia among domestic animals, while tick bites also reduce the quality of
      hides. However, the major losses caused by ticks are due to the ability to
      transmit protozoan, rickettsial and viral diseases of livestock, which are of
      great economic importance world-wide. The authors review general aspects of tick
      biology, the taxonomy, pathogenic effects and vector role of these species, and
      methods for the control of ticks. The distribution of ticks is continuously
      changing, as illustrated by the spread of the African tick Amblyomma variegatum
      in the Caribbean, where a large-scale eradication campaign is now under way.

PMID- 7711311
TI  - [Mange in domestic animals and methods of control].
AB  - The author reviews the control of various types of mange, principally in
      production animals (cattle, sheep, goats, camels, dromedaries, equines, pigs,
      rabbits and poultry). An account of the taxonomy, morphology and biology of the
      mange-causing parasites is followed by a study of the epidemiology and pathology
      of the various forms of mange. The author then examines the methods for control
      of these highly contagious cutaneous parasitic diseases, which cause considerable
      losses to animal production. The various control procedures are described:
      acaricides may be used as dips, showers or sprays, as a topical application to
      the back ('pour-on'), or administered by the parenteral route. The principal
      acaricides are reviewed. The author concludes by discussing the problems of
      resistance, the use of auxiliary therapeutic measures, and the possibilities for
      medical treatment and hygienic precautions.

PMID- 7711312
TI  - Insecticides and acaricides: resistance and environmental impact.
AB  - Insecticides continue to be the primary means of control for ectoparasites on
      livestock. Intensive use of these materials has led to resistance to
      organochlorines, organophosphates and pyrethroids among populations of Haematobia
      irritans irritans, H. irritans exigua and Lucilia cuprina. Similarly, use of
      acaricides has led to resistance in one-host Boophilus ticks to all currently
      used organophosphate-carbamates, synthetic pyrethroids and amidines. Resistance
      in multi-host ticks is less widespread. New chemicals are available for the
      control of resistant ectoparasites, but there are concerns over resistance and
      residues problems, which prompt the authors to discuss new pest management
      strategies. Environmental concerns are raised regarding the use of pesticides on
      livestock.

PMID- 7711313
TI  - Host resistance to ectoparasites.
AB  - Examples of immunological reactions to arthropod parasites include responses by
      hosts to the following stimuli: excretory and secretory antigens produced by
      myiasis-producing larvae or skin-dwelling (mange) mites salivary antigens of
      blood-sucking arthropods. In many cases, these are hypersensitivity reactions,
      which often appear not to produce very deleterious effects on the parasites.
      However, some reactions--such as those induced by natural infestations with
      ixodid ticks and certain mange mites--damage the parasites and protect the hosts.
      Recently, successful vaccines have been devised to protect cattle from Boophilus
      microplus ticks. The antigens used, which are believed not to be introduced into
      the host during natural infestations, came from the midgut of the ticks. Such
      antigens, which are normally 'concealed' from the host, appear to induce 'novel'
      immunological responses which are difficult for the parasite to combat. Similar
      'concealed' antigens have also been investigated in potential vaccines for use
      against other ectoparasitic arthropods.

PMID- 7711314
TI  - [Ectoparasites of animals: methods of ecological, biological, genetic and
      mechanical control].
AB  - The use of insecticides is still the basic procedure for controlling most
      ectoparasites, but various methods are being developed to act in addition to, or
      in synergy with these products, so as to enhance the efficacy and reduce the
      adverse effects of insecticides, by contributing to ecologically acceptable
      strategies. These methods are classified as ecological control (modification of
      the environment of the parasite), biological control (predation, parasitism,
      action of pathogens, etc.), genetic control (release of sterile males,
      hybridisation, genetic manipulations) and mechanical control (insect traps, use
      of repellents). The application of such methods depends on the biological and
      ecological characteristics of the ectoparasite, and they may act directly or
      indirectly, affecting mortality and/or reproduction. The authors review the
      principal methods applicable to major groups of ectoparasites of veterinary
      interest. Non-chemical methods are the subject of wide-ranging and promising
      research, particularly in view of recent developments in biotechnology.

PMID- 7711315
TI  - Integrated control of ectoparasites.
AB  - Integrated control of ectoparasites of veterinary importance is being implemented
      on a limited basis at present. However, several forces are accelerating a global
      shift to integrated pest management (IPM). These accelerating forces include the
      following: reduction in new chemical compounds registered for use on livestock
      and poultry universal development of resistance to pesticides heightened
      environmental sensitivities to exclusive dependence on pesticide-based control
      need for strategies which increase profits for the producer while decreasing
      costs to the consumer. Integrated pest control requires many technologies for
      incorporation into specific pest management systems. Individual components
      include new chemicals, formulations and delivery systems, biological control,
      mechanical control, immunological control, genetic control, and regulatory
      control. Computer simulation models based on a quantitative ecological database
      are invaluable in devising and monitoring IPM approaches to controlling
      ectoparasites which affect livestock and poultry. IPM strategies have been
      developed for pests of veterinary importance, but eventually these must be
      incorporated into total livestock production systems. For implementation, a
      number of major impediments to IPM must be overcome. These problems can best be
      solved through a vigorous technology transfer programme. In addition to face-to
      face meetings between producers and extension agents, the implementation of IPM
      can be further encouraged at producer group meetings, through education of animal
      health professionals, by the publication of articles in producer magazines, and
      by radio and television broadcasts to the agricultural sector. Research focusing
      on the development of cost-effective and environmentally-compatible IPM systems
      is necessary for future progress.

PMID- 7711316
TI  - Ectoparasites and classification.
AB  - The authors present an introductory overview of the principal groups of
      ectoparasites (flukes, leeches, crustaceans, insects, arachnids, lampreys and
      vampire bats) associated with domestic animals. Currently-accepted higher-level
      classifications are outlined for these parasites. Almost all significant
      ectoparasites of domestic animals are invertebrates, the majority being
      arthropods (crustaceans, insects and arachnids). Some of these ectoparasites are
      of particular importance as vectors of pathogens. Many ectoparasite species are
      host-specific, and vector species typically transmit characteristic pathogens.

PMID- 7711317
TI  - Immunocytochemical localization of the Ya, Yc, Yb1, and Yb2 subunits of
      glutathione S-transferases in the testis and epididymis of adult rats.
AB  - Glutathione S-transferases (GSTs) are dimeric proteins that come from a multigene
      family. They can be grouped into five classes (alpha, mu, pi, sigma, theta) based
      on the degree of amino acid homology of their subunits. These GST isozymes are
      able to catalyze the conjugation of glutathione with a wide variety of
      electrophiles, thereby protecting important cellular constituents from
      electrophilic attack. In the present study, the distribution of the Ya and Yc
      subunits from the alpha family, as well as the Yb1 and Yb2 subunits from the mu
      gene family was examined using immunocytochemistry in the adult rat testis and
      epididymis. The results of these four GST subunits were also compared with two
      other subunits, the Yf and Yo proteins, which have already been investigated in
      our laboratory [Veri et al. (1993), J. Androl., 14:23-44; Veri et al. (in press),
      J. Androl.]. In the testis, Leydig cells were intensely stained for all six
      subunits. Within the seminiferous epithelium, Sertoli cells were reactive only
      for antibodies raised against the Ya, Yb1 and Yf subunits. Among germ cells, all
      spermatogonia, spermatocytes and step 1-15 spermatids were virtually unreactive
      for each of the six GSTs. However, moderate to intense staining was seen over
      steps 16-19 spermatids with the anti-Yo and anti-Ya antibodies, and intense
      staining over step 19 spermatids with the anti-Yb1 and anti-Yb2 antibodies. In
      the rete testis, Yf, Yo, Yb1, and Yb2 subunits were intensely reactive over the
      epithelial cells with weak staining for Yc and no staining for Ya antibodies.
      Interestingly, in the efferent ducts the Yc, Yb1, and Yf proteins were intensely
      reactive over ciliated cells, whereas only the Yc protein was intensely reactive
      over nonciliated cells. In the epididymis, immunoreactivity varied among the
      principal and basal cells of a given epididymal region for each GST antibody. In
      the case of principal cells, several of the GSTs showed a similar immunostaining
      pattern along the tubule. Although not identical in intensity of reaction, the
      Yc, Yb1, Ya and Yo proteins showed an increase in staining intensity from the
      proximal to distal segments of the epididymis. In contrast, the Yb2 protein was
      intensely expressed only in the distal caput with weak levels throughout the rest
      of the epididymis. The Yf reactivity was strongest from the distal initial
      segment to the distal caput and unreactive in the corpus and proximal cauda
      epididymidis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7711318
TI  - Electron microscopic immunolocalization of the 18 and 29 kilodalton secretory
      proteins in the mouse epididymis: evidence for differential uptake by clear
      cells.
AB  - In previous studies we reported the synthesis, secretion, and immunolocalization
      at the light microscopic level of two mouse epididymal proteins, MEP 7 and MEP 10
      [Rankin et al. (1992b), Biol. Reprod., 46:747-766]. MEP 7 is the mouse homologue
      of the rat metalloproteins, AEG/D and E, and MEP 10 is the mouse homologue of the
      rat retinoic acid binding proteins, B and C. We now describe the
      immunolocalization of MEP 7 and MEP 10 in the mouse epididymis at the electron
      microscopic level. MEP 7 was localized in the Golgi apparatus, in small electron
      lucent secretory vesicles, and on microvilli of the principal cells from the
      distal caput epididymidis to the cauda. The luminal contents were also
      immunoreactive in these regions of the epididymis. Although some gold particles
      were associated with the sperm surface, there was no selective concentration of
      these particles. In addition, MEP 7 was localized in large (600 nm) supranuclear
      endocytic vesicles and in infranuclear lysosomes. MEP 10 immunoreactivity was
      also seen on the microvilli of the principal cells of the distal caput and corpus
      and the luminal contents from the distal caput to the cauda epididymidis. There
      was no association of gold particles with the sperm surface. In contrast to MEP
      7, there was no detectable MEP 10 immunoreactivity on the organelles of the
      principal cells involved in protein secretion or endocytosis. Clear cells also
      demonstrated immunoreactivity to MEP 7 and MEP 10. However, the intensity of
      immunolabeling, and the number of clear cells labeled, was greater with MEP 10
      than MEP 7. In the case of MEP 7, the gold particles were located on the large
      supranuclear endocytic vesicles and on some infranuclear lysosomes, from the
      proximal corpus to the middle cauda, while in the case of MEP 10, gold particles
      were predominantly present in infranuclear lysosomes from the distal caput to the
      middle cauda. These results suggest that the principal cells are involved in both
      the secretion and endocytosis of MEP 7. The MEP 10 and MEP 7 proteins present in
      the lumen of the mouse epididymis are endocytosed from the lumen and degraded in
      the clear cells. However, the process of endocytosis by the clear cells of these
      two proteins appears to be different.

PMID- 7711319
TI  - Freeze-fracture study of cell junctions in the epididymis and vas deferens of a
      seasonal breeder: the mink (Mustela vison).
AB  - The present study used the freeze-fracture technique and vascular infusion of
      horseradish peroxidase (HRP) as a junction permeability tracer, visible in thin
      sections, to investigate potential seasonal variations in the mink epididymis and
      vas deferens cell junctions. The junctions were studied in kits during the
      neonatal period, during and after puberty, and during adulthood monthly
      throughout the annual reproductive cycle. Results showed the existence, at the
      time of birth, of a junctional complex joining ductal cells that reached the
      lumen of the epididymis and vas deferens. The lumenal impermeable segment of the
      junctional complex was characterized by the presence of an occluding zonule made
      up of continuous tight junctional ridges extending around the perimeter of the
      cell. The basal permeable segment of the junctional complex contained mainly
      discontinuous ridges with frequent forming gap and tight junctions next to
      adhering junctions. Receding annular junctions were present in the apical and
      lateral cytoplasm of principal and clear cells. The membrane domain apical to the
      occluding zonule bore 30-35 nm exo/endocytosis blebs and 40-60 crenations
      associated with deforming tight and gap junctions made up of randomly scattered
      particles. Patterns of junctional strands varied greatly from one principal
      and/or clear cell to another. However, cell junctions did not significantly vary
      from the neonatal period to adulthood nor from breeding to testicular regression.
      Anatomical subdivisions of the epididymis with fewer junctional strands per
      zonule and high diversity in their patterns exhibit no permeability differences
      to HRP when compared with subdivisions containing more numerous strands. The
      junctions were impermeable during the neonatal period and throughout the annual
      reproductive cycle. The following conclusions were reached: 1) a competent
      occluding zonule developed in the mink epididymis and vas deferens before it did
      in the testis; 2) the number of strands and the diversity of patterns did not
      correlate with permeability differences; 3) after the development of a lumen in
      the testicular excurrent duct, neither receding cellular changes caused by
      testicular regression nor seasonal passage of a bolus of sperm through the duct
      modified the occluding zonules; and 4) in the testicular excurrent duct, junction
      modulation (i.e., formation and deformation) paralleled that in the testis and
      followed the direction of the synthesis-transport-secretion process.

PMID- 7711320
TI  - Structure and turnover of junctional complexes between principal cells of the rat
      epididymis.
AB  - The epididymal junctional complex between adjacent principal cells is composed of
      apically located gap, adherens and tight junctions. Tight junctions between
      adjacent epithelial cells lead to the formation of the blood-epididymal barrier.
      The objectives of this study were to examine the structure of the epididymal
      junctional complex in the different regions of the epididymis and to review the
      regulation of epithelial cadherin in the rat epididymis. Changes in the structure
      of the junctional complex, at the level of the electron microscope, were evident
      when comparing the initial segment to other regions of the epididymis. In the
      initial segment, the tight junction spanned a considerable length of the apical
      plasma membrane but had few desmosomes. In the other regions of the epididymis,
      the span of merging plasma membranes was considerably reduced, but in these
      regions, numerous desmosomes were present in the apical region. Several examples
      of what appeared to be a loss of portions of the plasma membrane of adjacent
      principal cells were evident along the entire epididymis. Such images as the
      invagination of a portion of the lateral plasma membrane of one principal cell
      into another, constriction of the invaginated area and eventual detachment
      leading to the formation of annular junctions suggest that there is a turnover of
      plasma membranes. The formation of cellular junctions involves the interactions
      of cell adhesion proteins followed by the addition of junctional proteins which
      assemble into tight and gap junctions. Epithelial cadherin (E-Cad), a calcium
      dependent cell adhesion protein, was localized to the principal cells of the
      epididymis. Immunocytochemistry at the level of the electron microscope showed
      that E-Cad was present between the lateral plasma membranes of adjacent principal
      cells, both in the region of the junctional complex and in the deeper lying
      areas. E-Cad was also present in annular junctions located in close proximity to
      the junctional complex, indicating that these structures were related to the
      plasma membrane. E-Cad mRNA levels are regulated during postnatal epididymal
      development. In the caput-corpus epididymidis, E-Cad mRNA concentrations increase
      to peak at 42 days of age. This is well correlated with the conversion of
      testosterone to dihydrotestosterone in the epididymis. In the cauda epididymidis,
      however, E-Cad mRNA concentrations do not increase as a function of age,
      indicating that this protein is regulated in a segment-specific manner.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7711321
TI  - Epididymal epithelium: its contribution to the formation of a luminal fluid
      microenvironment.
AB  - To understand the process of sperm maturation, an understanding of interactions
      between the spermatozoa with the luminal fluid microenvironment and with the
      epididymal epithelium is necessary. The composition of epididymal luminal fluid
      of several species is well documented but the manner by which the epididymis
      contributes to the formation of this specialized milieu is not so well
      understood. A major role played by the epididymis is to finely regulate the
      movement of molecules into and out of the lumen. This ensures that as spermatozoa
      progress along the duct they are exposed to a continually changing, but optimal
      environment necessary for their maturation and survival. This review focusses on
      our current understanding of the contributions of the epididymal epithelium to
      the formation of a specialized luminal fluid microenvironment. The role of the
      blood-epididymis barrier, the composition of the epididymal luminal fluid, the
      permeability properties of the epididymal epithelium, and recent studies on a
      number of luminal fluid proteins and expression of the genes which encode these
      proteins are discussed.

PMID- 7711323
TI  - Microscopy of high temperature superconductors, Part I. Introduction.

PMID- 7711322
TI  - Effects of vasectomy on the epididymis.
AB  - Common principles can be discerned in the response of the epididymis to
      vasectomy, despite species differences. Increases in the size and number of
      lysosomes are the most frequent changes in the epididymal epithelium. The
      presence or absence of additional alterations such as changes in the height of
      the epithelium may be related to variations in distensibility of the vas deferens
      and epididymis. Direct measurements by micropuncture of epididymal and
      seminiferous tubule hydrostatic pressure indicate that, contrary to dogma,
      increased pressure in the distal epididymis after vasectomy is not generally
      transmitted to the seminiferous tubules. The epididymal interstitium shows
      microscopic changes indicative of chronic inflammation, with infiltration of
      macrophages, lymphocytes, and plasma cells, and rats with these lesions have
      higher antisperm antibody levels than animals lacking epididymal changes.
      Macrophages and neutrophils may enter the duct through the epididymal epithelium,
      at sites of rupture of the duct, and in the efferent ductules. Cyst-like
      spermatic granulomas occur in virtually all species where the epididymis or vas
      deferens ruptures with escape of spermatozoa. The sites and timing of granuloma
      formation may depend on the mechanical properties of the tract in different
      species, and they are probably important in the immune response to vasectomy.
      Postvasectomy sera in Lewis rats recognize a consensus repertoire of dominant
      autoantigens that closely resembles the antigens bound by sera from rats
      immunized with isologous spermatozoa. There are multiple routes for disposal of
      the sperm that continue to be produced after vasectomy.

PMID- 7711324
TI  - Structural investigations of recently discovered high Tc superconductors.
AB  - A short overview is given of the possibilities of electron microscopy in the
      determination of the local, atomic scale structure of high Tc superconducting
      materials. Examples include the detection of weak oxygen ordering, description
      and characterization of deformation modulations in layered superconductors, and
      analysis of very long period superstructures. The ordering principles for
      tetrahedral chains in Ga-, Co-, or Al-substituted YBCO are discussed and their
      complex defect structures are described. The incommensurate modulation in YBCO
      based materials containing SO4-tetrahedra, centered on the Cu(1) sites of the CuO
      chain plane, is attributed to the ordering of b-oriented SO4-rich chains in the
      Cu(1)-S-O layer; the structure is described in terms of an SO4-concentration
      wave. As examples of the new mercury-based superconducting family we discuss
      Y0.6Ca0.4Ba2Hg1-xMxCu2O6+y, which crystallizes in the space group P4/mmm with a =
      0.3870(1) nm, c = 1.2537(1) nm. This cuprate belongs to the 1212 series;
      susceptibility measurements show a Tc (onset) of 90K, with a diamagnetic volume
      fraction of 27% at 4.2K to be reached. A second example is related to the
      compound Tl2HgBa4Cu2O10+y, in which ordering between single Hg layers and double
      Tl layers is observed.

PMID- 7711325
TI  - HREM study of the crystal chemistry of the alkaline-earth cupric oxides
      stabilized at high pressure.
AB  - The crystal chemistry of the alkaline-earth cupric oxides stabilized at high
      pressure was studied by high-resolution electron microscopy. Two families of
      superconductors, (Ca1-ySry)1-xCuO2 and Srn+1CunO2n+1+delta (n = 1, 2), and one
      series of semiconductors, Srn-1Cun+1O2n, are reported. Their structural
      characteristics are systematically interpreted on the basis of the simple
      infinite-layer structure seen in SrCuO2. Microstructures and their relevance to
      high-Tc superconductivity are discussed, particularly in the alkaline-earth
      deficient infinite-layer phase.

PMID- 7711326
TI  - Copper oxycarbonates with layered structures, a new class of high Tc
      superconductors.

PMID- 7711327
TI  - Direct observations of arrangements of carbonate groups in oxycarbonate
      superconductors by high-resolution electron microscopy.
AB  - Arrangements of CO3 groups in various types of oxycarbonate superconductors are
      examined by high-resolution transmission electron microscopy (HRTEM). Every other
      B-site of basic perovskite structure is replaced with CO3 groups in the first
      carbonate superconductor, (Ba0.56Sr0.44)2Cu1.1(CO3)0.9Oy. The 123-related
      oxycarbonate superconductor obtained in a Y-Ca-Sr-Cu-O system,
      (Y0.475Ca0.475Sr0.05)Sr2Cu2.4(CO3)0.6Oy, has a superstructure with 2a periodicity
      due to ordered replacements of Cu-site with CO3 groups. The non-superconducting
      counterpart with 123-related structure, (Y0.84Sr0.16)2Sr2Cu2.6(CO3)0.4Oy, on the
      other hand, shows more disordered arrangements of CO3 groups with nearly 3a
      periodicity. Similar superstructures, due to ordered replacements of Cu sites
      with CO3 groups, are also observed in the 223-related oxycarbonate
      superconductors, (Ln,Ce)2Sr2Cu2.5(CO3)0.5Oy (Ln = Ho, Dy). Homologous series of
      compounds, (CaSr)n+1Cun(CO3)Oy (n = 1-5), consist of alternate stacking of
      Sr2Cu(CO3)Oy and SrCuO2 (infinite-layer) types of blocks. They become
      superconductive by additionally doping the BO3 group. Another homologous series
      of Bi-based oxycarbonate superconductors, (Bi,Pb)2Sr2n+2Cun+1 (CO3)nOy (n = 1-3),
      contain alternate CuO2 and CO3 layers in between the two (BiO)2 layers. Both
      mercury (Hg)- and thallium (TI)-based oxycarbonate superconductors,
      MBa2Sr2Cu2(CO3)Oy (M = Hg or Tl) show quite unique modulation structures, where
      both HgO (or TlO) and CO3 layers repeat in the same plane, along [110] in the Hg
      compound and [100] in the Tl compound, to form long-period superstructures with
      wavy distortion of atom planes.

PMID- 7711328
TI  - Preparation of oxide superconductor specimens for TEM examination.
AB  - We have investigated a wide variety of oxide superconductors and report here on a
      number of techniques that can be effectively used to prepare transmission
      electron microscopy (TEM) specimens from these materials. Crushing, cleaving, ion
      milling, ultramicrotomy, and jet polishing all were successfully utilized, and
      details of each technique, as well as equipment used, are described. Selection
      among these methods depends both on the starting form of the material and the
      information required. Ion milling and crushing generally give the best results
      and have the widest applicability in our particular work, while crushing and
      cleaving involve the least equipment cost. In some cases, particularly with ion
      milling and jet polishing, small variations in the details of preparation have a
      dramatic effect on the success rate. We have found it to be a great advantage
      that the same techniques can be applied in a similar manner to a whole range of
      oxide materials, even (with some refinements and special precautions) to those
      that are extremely oxygen or moisture sensitive.

PMID- 7711329
TI  - Shadow images for in-line holography in a STEM instrument.
AB  - In a dedicated STEM instrument equipped with a field emission gun, shadow images
      are easily obtained and have many uses. They are very sensitive to misalignment
      of the instrument and astigmatism, and therefore can be used for rapid and
      accurate alignment of the microscope. For crystalline materials, the shadow image
      contains both the bright-field and dark-field images. It is a summation of the
      transmitted and diffracted beams, and is basically a kind of Gabor's in-line
      hologram. Under small or medium defocus, shadow images of a thin, well-orientated
      crystalline specimen take the characteristic form of Ronchigrams, which offer a
      unique means to calibrate the microscope operation parameters, such as the
      spherical aberration coefficient Cs and defocus settings of the objective lens,
      with high accuracy. With the calibrated values of Cs and delta, a transfer
      function of the objective lens may be generated. In the stage of numerical
      reconstruction, by adapting this transfer function to the experimentally recorded
      hologram the lens aberration introduced in forming the hologram may be corrected
      and an improved resolution may be achieved for electron microscope images.

PMID- 7711331
TI  - The spirillas.

PMID- 7711330
TI  - For whom the clock ticks.

PMID- 7711332
TI  - The addict from Xanadu (Samuel Taylor Coleridge).

PMID- 7711333
TI  - Idiopathic normal pressure hydrocephalus: a revisionist interpretation.

PMID- 7711334
TI  - Hereditary factors in sarcoidosis.

PMID- 7711335
TI  - Physicians newly licensed in RI during 1993.
AB  - The physicians newly licensed in 1993 are a well-trained cohort, typically board
      certified, and in their mid-thirties. Only a minority (about 9%) were born in
      Rhode Island although a substantial plurality had been educated at Brown and its
      teaching hospitals. About one-third of these 259 physicians had never previously
      held medical licenses. Hence, the Rhode Island license represents their
      credentialled entrance into the independent practice of medicine.

PMID- 7711336
TI  - The relative effects of malpractice liability, cigarette consumption, and
      physician income on state health care expenditures.

PMID- 7711337
TI  - Mortality and years of productive life lost.

PMID- 7711338
TI  - American Society for Artificial Internal Organs. 41st annual conference, May 4-6,
      1995, Chicago, Illinois. Abstracts.

PMID- 7711339
TI  - Salivary concentrations of ketoconazole and fluconazole: implications for drug
      efficacy in oropharyngeal and esophageal candidiasis.
AB  - OBJECTIVE: To determine whether salivary concentrations of ketoconazole and
      fluconazole may explain the apparent disparity between in vitro activity and
      clinical efficacy observed with these drugs. DESIGN: Healthy subjects received a
      single oral dose of ketoconazole 400 mg or fluconazole 100 mg in a randomized,
      crossover fashion. Saliva was collected at 0, 1, 2, 3, 6, 12, and 24 hours. Blood
      samples were obtained at 2 and 24 hours. Salivary concentrations and plasma
      concentrations for each drug were determined by HPLC. Minimum inhibitory
      concentration (MIC) testing was determined in triplicate on 6 clinical isolates
      of Candida albicans, and times over the median MIC values were calculated.
      PARTICIPANTS: Eight subjects completed the study. RESULTS: The mean (+/- SD) peak
      salivary concentration for ketoconazole was 0.119 +/- 0.050 microgram/mL at 3
      hours; no subject had a detectable ketoconazole salivary concentration at 24
      hours. At 2 and 24 hours, mean ketoconazole plasma concentrations were 7.64 +/-
      3.87 and 0.11 +/- 0.05 microgram/mL, respectively. The saliva to plasma
      concentration ratio at 2 hours was 0.01. The mean peak salivary concentration of
      fluconazole was 2.56 +/- 0.34 microgram/mL at 3 hours. At 24 hours, the mean
      salivary concentration was 1.44 +/- 0.33 microgram/mL. At 2 and 24 hours, mean
      fluconazole plasma concentrations were 4.39 +/- 3.33 and 3.72 +/- 2.83
      micrograms/mL, respectively. The saliva to plasma concentration ratio at 2 hours
      was 0.55. Median MIC values were 0.0625 microgram/mL (range 0.0313-0.125) for
      ketoconazole and 0.25 microgram/mL (range 0.125-0.5) for fluconazole. Calculated
      times over which ketoconazole and fluconazole exceeded the median MICs in saliva
      were approximately 13 and greater than 24 hours, respectively. CONCLUSIONS: After
      a single oral dose, fluconazole achieved higher salivary concentrations than did
      ketoconazole. This may explain the increased clinical efficacy of fluconazole in
      the treatment of oropharyngeal-esophageal candidiasis when compared with
      ketoconazole.

PMID- 7711340
TI  - Assessment of chemotherapy-induced emesis and evaluation of a reduced-dose
      intravenous ondansetron regimen in pediatric outpatients with leukemia.
AB  - OBJECTIVE: To measure the severity of nausea and vomiting in pediatric patients
      receiving intravenous or intrathecal chemotherapy for acute lymphoblastic
      leukemia and to evaluate the effectiveness of 2 intravenous doses of ondansetron
      for this condition. DESIGN: Patients were surveyed during repeated treatments of
      maintenance chemotherapy, given with or without ondansetron, using a repeated
      measures pretest/posttest design. SETTING: Outpatient pediatric oncology clinic.
      PATIENT POPULATION: Sixteen pediatric patients (aged 2-15 years, mean 6.2) with
      acute lymphoblastic leukemia. METHODS: Surveys to assess nausea and vomiting and
      the extent of interference with daily activities were administered following
      emetogenic chemotherapy with or without ondansetron. RESULTS: A total of 255
      surveys following emetogenic chemotherapy with daunorubicin, cyclophosphamide,
      carmustine, and etoposide and cytarabine combined, as well as intrathecal therapy
      with methotrexate, hydrocortisone, and cytarabine, were analyzed. Analysis was
      performed on surveys of 149 courses without antiemetic therapy and 106 courses
      after 2 doses of ondansetron 0.15 mg/kg iv. The most emetogenic chemotherapy
      treatment was the etoposide/cytarabine combination (p < 0.05). Ondansetron
      completely protected patients (defined as no nausea or no vomiting) during most
      (> 50%) of the chemotherapy treatments, except for those in which
      cyclophosphamide was used. Ondansetron provided greater control of nausea and
      vomiting, a higher percentage of complete protection, and decreased the daily
      activity interference rating for carmustine and etoposide/cytarabine compared
      with courses of chemotherapy without antiemetics (p < 0.05). Two intravenous
      doses of ondansetron also provided durable antiemetic efficacy over time for the
      most emetogenic chemotherapy treatment (etoposide/cytarabine). CONCLUSIONS:
      Etoposide/cytarabine proved to be the most emetogenic of the chemotherapy
      treatments studied. A reduced-dose regimen of intravenous ondansetron was shown
      to be an effective antiemetic for the outpatient treatments with
      etoposide/cytarabine and carmustine, but not with cyclophosphamide.

PMID- 7711341
TI  - Paromomycin-associated pancreatitis in HIV-related cryptosporidiosis.
AB  - OBJECTIVE: To report a case of pancreatitis related to paromomycin
      administration. CASE SUMMARY: A 39-year-old man with AIDS developed pancreatitis
      concurrent with successful treatment of intestinal cryptosporidiosis with
      paromomycin. The hyperamylasemia resolved with discontinuation of the agent and
      recurred when paromomycin treatment was reinstituted. DISCUSSION: To our
      knowledge, this is the first reported case of pancreatitis believed to be induced
      by paromomycin. Although pancreatitis in HIV-infected patients has multiple
      causes, the nature of this case suggests the involvement of paromomycin. The
      mechanism of action is unclear. CONCLUSIONS: Pancreatitis should be considered in
      the differential diagnosis of abdominal pain in patients who are treated with
      paromomycin.

PMID- 7711342
TI  - Continuous midazolam infusion for the management of morphine-induced myoclonus.
AB  - OBJECTIVE: To describe a patient with morphine-induced myoclonus treated with a
      continuous infusion of midazolam and continued morphine dose escalation. DESIGN:
      Single case report. SETTING: Delivery, monitoring, and titration of morphine and
      midazolam in the patient's home by a homecare agency. RESULTS: The use of high
      dosages of morphine (i.e., 500 mg/h) produced myoclonic spasms in this patient,
      which in turn resulted in increasing pain. To allow for continuation of effective
      analgesia and to control the myoclonic spasms, an infusion of midazolam was
      initiated and titrated. The midazolam infusion allowed for continuation of the
      morphine dosage and also permitted further dosage escalation. As morphine dosages
      were further escalated, it was also necessary to increase the midazolam infusion
      to control additional myoclonic spasms. CONCLUSIONS: Use of a concomitant
      midazolam infusion with high doses of morphine appears to be safe and is an
      effective means of controlling morphine-induced myoclonus. If further dosage
      increase of morphine are necessary in this setting, increases in the midazolam
      infusion also may be required.

PMID- 7711343
TI  - Probable ticlopidine-induced cholestatic hepatitis.
AB  - OBJECTIVE: To report a case of probable ticlopidine-induced cholestatic
      hepatitis. CASE SUMMARY: A 76-year-old man with no known history of liver disease
      developed painless jaundice approximately 3 weeks after starting ticlopidine 250
      mg bid. After ticlopidine was discontinued, the jaundice resolved and serum liver
      enzyme concentrations returned toward normal. A diagnosis of probable ticlopidine
      induced cholestatic hepatitis was made. The patient was not rechallenged with
      ticlopidine. DISCUSSION: A literature search produced 6 case reports describing 7
      patients in whom probable ticlopidine-induced cholestatic hepatitis had been
      diagnosed. Only 1 of these reports appeared in the North American literature.
      Jaundice developed within 1 to 3 months of starting ticlopidine at less than or
      equal to the recommended daily dose. In all cases, jaundice resolved and serum
      liver enzyme concentrations normalized over a period of months after drug
      discontinuation. CONCLUSIONS: Routine monitoring of serum liver enzyme
      concentrations is not recommended. However, patients should be instructed to
      watch for signs and symptoms of liver injury. Should they occur, patients should
      stop taking the ticlopidine and consult their physician immediately.

PMID- 7711344
TI  - Monitoring of intravenous quinidine infusion in the treatment of Plasmodium
      falciparum malaria.
AB  - OBJECTIVE: To report a case of Plasmodium falciparum malaria in which intravenous
      quinidine was used, resulting in a prolonged QT interval. CASE SUMMARY: P.
      falciparum malaria was diagnosed in a woman visiting from Nigeria. Treatment was
      instituted with intravenous quinidine given the high level of parasitemia. During
      the quinidine infusion, the patient experienced a prolonged QT interval and an
      episode of supraventricular tachycardia. The infusion rate was decreased and the
      QT duration returned to normal; there was no further episode of arrhythmia.
      Subsequently the patient was given oral quinine. Her condition improved and she
      was discharged on day 4 of therapy. DISCUSSION: P. falciparum malaria, not
      commonly seen in the US, is associated with severe morbidity and mortality. This
      condition necessitates prompt treatment with intravenous quinidine, which can be
      associated with toxicity. The use of this agent to treat malaria is reviewed
      herein. CONCLUSIONS: In patients with P. falciparum malaria, a high-level
      parasitemia may require treatment with a potentially toxic agent, intravenous
      quinidine. Cardiac monitoring of these patients is essential during such therapy.

PMID- 7711345
TI  - Autism and associated behavioral disorders: pharmacotherapeutic intervention.
AB  - OBJECTIVE: To review the literature on autism and pervasive developmental
      disorders (PDDs) as well as their respective pharmacotherapies. DATA SOURCES: An
      Index Medicus, MEDLINE, and bibliographic search of the literature pertaining to
      autism, PDDs, and respective treatments. STUDY SELECTION: Because of the paucity
      of literature on the treatment of autism and PDDs, the selection of reported data
      for this review included both controlled and uncontrolled studies, as well as
      case reports and any other information reported in the literature on the
      treatment of these disorders. DATA SYNTHESIS: Autism and PDDs are severe
      developmental disabilities defined by behavioral criteria. These disorders are
      lifelong in nature and present in varying severity of clinical manifestations.
      Behavioral manifestations of patients with autism include core deficits in social
      interaction, communication, and imaginative activities, with a restricted
      repertoire of activities and interests. The present understanding of the
      neurochemical basis of the disorder is limited. The role of pharmacotherapy in
      the management of autism and PDDs is to ameliorate behavioral symptoms that
      interfere with the patient's ability to participate in educational, social, work,
      and family systems. Agents that have shown positive clinical effects in the
      treatment of children with autism and PDDs are reviewed in this article.
      CONCLUSIONS: Autism is a complex developmental disorder representing a
      heterogeneous group of individuals with similar symptomatologies and multiple
      biologic etiologies. Present pharmacotherapeutic intervention seeks to resolve
      behavioral symptoms. Treatment of autism and PDDs requires appropriate
      delineation of the behaviors and neurobiologic disorders associated with each
      patient. No single therapeutic agent, or combination thereof, is appropriate for
      the treatment of all children and adults with autism or PDDs.

PMID- 7711346
TI  - Pharmacist-managed, physician-directed asthma management program reduces
      emergency department visits.
AB  - OBJECTIVE: To determine whether the number of emergency department (ED) visits
      for acute asthma exacerbations could be decreased by providing patients with a
      comprehensive program of asthma management delivered by a pharmacist and a
      physician. DESIGN: Patients were selected from the ED and asked to attend a
      special asthma clinic that provided education about asthma and proper use of
      asthma medications, regular telephone contact between the pharmacist and patient,
      and an open-door clinic policy. SETTING: A university-affiliated urban teaching
      hospital. PARTICIPANTS: The study population consisted of 25 asthmatic patients
      who were at least 18 years of age and who were seen in the ED a minimum of 3
      times in a 12-month period. MAIN OUTCOME MEASURES: The number of visits to the ED
      for acute exacerbations of asthma was measured. Patients served as their own
      controls. The number of ED visits for asthma during the 6-month study period was
      compared with two 6-month periods prior to the study period for each patient.
      RESULTS: The total number of ED visits for the 25 enrolled patients six months
      prior to their enrollment into the study was 92; the number of ED visits during
      the same months of the study in the prior year was 47. During the study period,
      there were only 6 ED visits for asthma exacerbations. CONCLUSIONS: The
      comprehensive asthma management program reduced the number of ED visits for acute
      exacerbations of asthma.

PMID- 7711347
TI  - Hantavirus pulmonary syndrome: the Four Corners disease.
AB  - OBJECTIVE: To review the epidemiology, pathogenesis, clinical features,
      diagnosis, and treatment of hantavirus infections, focusing on the recent
      outbreak of hantavirus pulmonary syndrome in the US. DATA SOURCES: A MEDLINE
      search (1966 to present) of English language literature pertaining to
      hantaviruses was performed. Additional literature was obtained from reference
      lists of pertinent articles identified through the search. STUDY SELECTION AND
      DATA EXTRACTION: All articles were considered for possible inclusion in the
      review. Pertinent information, as judged by the authors, was selected for
      discussion. DATA SYNTHESIS: Hemorrhagic fever with renal syndrome (HFRS) has long
      been recognized in Eurasia and is the predominant disease manifestation of
      hantavirus infection worldwide. Hantavirus pulmonary syndrome (HPS) recently has
      been described in the US and exhibits greater pulmonary involvement and mortality
      than HFRS. Historically, 4 hantavirus serotypes (Hantaan, Seoul, Puumala,
      Prospect Hill) are recognized; however, additional serotypes have been proposed
      as distinct serogroups, including the serotype responsible for HPS in the Four
      Corners area: the Four Corners virus (FCV). Phylogenetic analysis shows that FCV
      is most closely related to Prospect Hill virus, another hantavirus previously
      isolated in the US that has not yet been identified with human disease.
      Additional hantavirus serotypes isolated in the US may provide insight into the
      prevalence of hantavirus infection and disease in this country. Inhalation of
      aerosolized virus is the predominant mechanism of hantavirus infection. Diagnosis
      is based primarily on clinical findings and serologic evidence of hantavirus
      antibody or direct evidence in clinical tissue specimens. Limited clinical
      studies evaluating ribavirin as a therapeutic modality demonstrated that the
      agent improves clinical outcome in HFRS. However, the role of ribavirin in the
      treatment of HPS remains to be determined. CONCLUSIONS: Hantavirus infections are
      becoming increasingly recognized as a cause of disease worldwide. Recognition of
      hantavirus disease in the US suggests enzoonosis of pathogenic hantaviruses. In
      the absence of a well-established cure, early diagnosis is imperative so that
      aggressive supportive care can be initiated.

PMID- 7711348
TI  - Recent advances in pediatrics.
AB  - The challenging issues in pediatric pharmacotherapy are both profound and
      exciting. Microtechnologies for evaluating the impact of genetics in disease
      (e.g., using polymerase chain reactions) and the possibilities of therapeutic
      interventions create major clinical and ethical dilemmas that remain to be
      resolved. Inclusion of pediatric patients in drug development and marketing
      trials also remains a point of contention. Finally, well-established therapies
      should not be overlooked in favor of new but unestablished treatment approaches.
      Future columns will continue to use the current format, in which a few selected
      topics of high therapeutic importance are discussed. The research technologies,
      discussion of new drug therapy interventions, and preventive strategies most
      likely to benefit the health care of infants, children, and adolescents will
      remain the scope of this column.

PMID- 7711349
TI  - Heparin inhalation for asthma.
AB  - The study of inhaled heparin in asthma has resurfaced recently in the medical
      literature. Although the above mentioned investigations have helped us better
      understand the pathologic processes of asthma, the results are too scant and
      preliminary to enable us to recommend the use of inhaled heparin in acute or
      chronic asthma. If the antiinflammatory properties of inhaled heparin prove to be
      of clinical value in asthma, it would represent a considerable advantage over
      steroids, which cause immunosuppression and other significant adverse reactions.
      Future trials will need to address such issues as: (1) What is the asthma
      subpopulation in which heparin is likely to be beneficial? (2) What is the
      optimal dose for inhalation? (3) What are the long-term adverse effects of
      inhaled heparin? (4) What is the optimal timing of administration with regard to
      allergen exposure? (5) If proven useful, what is the ideal delivery mode?
      Additional well-designed human trials will be necessary before we can define the
      place of inhaled heparin in the therapy or prevention of asthma.

PMID- 7711350
TI  - Extrapyramidal symptoms associated with calcium-channel blockers.
AB  - Flunarizine and cinnarizine have been well documented to cause EPS. Other CCBs,
      on rare occasions, also have been reported to cause EPS. Theoretical explanations
      for these events include the inhibition of calcium influx into striatal cells and
      direct dopaminergic antagonistic properties. In addition, the chemical structures
      of flunarizine and cinnarizine, which are related to neuroleptics, may explain
      the relatively greater incidence of EPS with these agents. Suggested risk factors
      for acquiring EPS with flunarizine or cinnarizine use appear to be age, although
      experience with using these agents in younger patients is limited, and a family
      history of tremors and/or Parkinson's disease. The onset and type of presentation
      is unpredictable and, in most instances, discontinuation of the medication
      relieves the symptoms within a few days to months. Pharmacologic management of
      EPS with continued use of the offending agent generally has not been of clinical
      benefit. In conclusion, patients receiving CCBs, particularly flunarizine and
      cinnarizine, should be monitored for EPS.

PMID- 7711351
TI  - Effect of clenbuterol on athletic performance.
AB  - Unlike inhaled beta 2-agonists, more studies need to be performed before the
      action of systemic beta 2-agonists on athletic performance can be assessed
      accurately. Experiments in animals with oral clenbuterol have shown augmentation
      in muscle bulk across numerous species, but human studies cannot confirm similar
      muscle mass enlargement in healthy men. Although the human studies demonstrate
      the potential for long-acting systemic beta 2-agonists to increase muscle
      strength in certain muscle fiber types, it is difficult to judge the drugs'
      effects on overall athletic performance, because athletic skill is more than
      strength, speed, and endurance. The effect of oral clenbuterol on athletic
      performance cannot be evaluated from its actions on muscle strength alone.
      However, as evidence stands now, sports regulatory agencies are correct to ban
      systemic beta 2-agonists until the following 2 points can be proven: (1) oral
      forms provide a therapeutic benefit that cannot be obtained with aerosol or
      inhaled forms; and (2) oral forms do not give any unfair advantage to the
      competitor in muscle strength, power output, or endurance. Provided they are
      administered as prescribed, aerosol or inhaled beta-agonists do not impart an
      unfair advantage or enhance athletic performance and can continue to be used in
      competition by athletes with EIA.

PMID- 7711352
TI  - Clinical interpretation of urine cocaine and metabolites in emergency department
      patients.

PMID- 7711353
TI  - Exfoliative dermatitis related to omeprazole.

PMID- 7711354
TI  - Effect of phenytoin on phenobarbital pharmacokinetics in a patient with epilepsy.

PMID- 7711355
TI  - Ciprofloxacin-induced Henoch-Schonlein purpura.

PMID- 7711356
TI  - Comment: misadventures with activated charcoal.

PMID- 7711357
TI  - Treatment of uncontrolled crying after stroke.
AB  - Uncontrolled crying after stroke is a disturbance of the motor concomitants of
      emotional affect. It manifests as stereotyped outbursts of crying that are
      excessive to an appropriate emotional response. The episodes can be triggered by
      almost any kind of emotional stimulus (happiness, excitement, sadness, just being
      looked at or talked to, the sight of a doctor, etc.) and can even occur without
      any obvious external or internal stimulus. The condition is socially
      embarrassing, and in the most severely affected patients the crying episodes can
      be so violent that they interfere with rehabilitation. Although frequent (1-year
      incidence is 20%), the condition often goes unrecognised because patients and
      relatives rarely complain about it spontaneously. Effective treatment has now
      been documented in 3 controlled studies of tricyclic antidepressants and the
      selective serotonin reuptake inhibitor citalopram. There seems to be a rationale
      for the latter approach to treatment, in that post-stroke pathological crying may
      be attributable to stroke-induced partial destruction of the serotonergic raphe
      nuclei in the brainstem or their ascending projections to the hemispheres.
      Although our knowledge of the aetiology and treatment of the condition is
      limited, and the need for further study is considerable, the present treatment
      possibilities can significantly improve quality of life for patients with this
      socially embarrassing and sometimes debilitating condition.

PMID- 7711358
TI  - The management of ventricular arrhythmias in older patients after CAST.
AB  - Asymptomatic nonsustained ventricular tachycardia and complex ventricular
      arrhythmias in elderly persons without heart disease should not be treated with
      antiarrhythmic drugs. Nonsustained ventricular tachycardia and complex
      ventricular arrhythmias in elderly persons are associated with an increased
      incidence of coronary events, primary ventricular fibrillation and sudden cardiac
      death, especially if abnormal left ventricular ejection fraction, left
      ventricular hypertrophy or silent ischaemia are present. beta-Blockers should be
      used in the treatment of elderly patients with ventricular tachycardia or complex
      ventricular arrhythmias associated with ischaemic or nonischaemic heart disease
      if there are no contraindications to beta-blocker therapy. I would reserve the
      use of amiodarone in the treatment of ventricular tachycardia or complex
      ventricular arrhythmias to life-threatening ventricular tachyarrhythmias in
      elderly patients who cannot tolerate or who do not respond to beta-blockers.
      Angiotensin converting enzyme (ACE) inhibitors should be used in treating elderly
      patients with ventricular tachycardia or complex ventricular arrhythmias
      associated with congestive heart failure. In patients with ventricular
      tachycardia or complex ventricular arrhythmias associated with asymptomatic left
      ventricular systolic dysfunction, I would use beta-blockers plus ACE inhibitors.
      If elderly patients have life-threatening, recurrent ventricular tachycardia or
      ventricular fibrillation resistant to antiarrhythmic drugs, invasive intervention
      is indicated. Until the results of prospective, randomised, clinical trials
      evaluating the automatic implantable cardioverter-defibrillator are available, I
      recommend using the automatic implantable cardioverter-defibrillator in elderly
      patients who have medically refractory sustained ventricular tachycardia or
      ventricular fibrillation.

PMID- 7711359
TI  - Diabetic neuropathy in the elderly.
AB  - Neuropathy is the most common symptomatic chronic complication in diabetic
      patients and accounts for substantial morbidity in the diabetic population. It is
      predominently a disease of the older diabetic population, and shows a progressive
      course with limb amputation as the final end-point of the disease. Pathologically
      the disorder is characterised by progressive degeneration as well as impaired
      regenerative ability of peripheral nerve fibers, resulting in a progressive loss
      and dying-back of the longest nerve fibres innervating the distal limbs. These
      changes are associated with progressive impairment of nerve function leading to
      impaired sensitivity in the limbs, which sometimes is associated with troublesome
      pain. Qualitatively similar but much milder functional and structural changes
      occur during normal aging processes, which potentially could make elderly
      diabetic patients more susceptible to an additional hyperglycaemic insult. The
      mechanisms underlying the development of diabetic neuropathy involve
      hyperglycaemia-induced metabolic abnormalities of peripheral nerve fibres and the
      supporting nutritive vascular supply. One of the major abnormalities involves
      activation of the polyol pathway with subsequent impairments in nerve function
      and vascular supply. Since hyperglycaemia appears to be the major culprit in the
      development of diabetic neuropathy, good glycaemic control is paramount in the
      long term treatment of diabetic patients to attenuate the development and/or
      progression of the disorder. Furthermore, elimination of risk factors such as
      obesity, smoking and excessive alcohol (ethanol) consumption, as well as patient
      education, are all important factors in the care of diabetic patients. In
      symptomatic neuropathic patients, including those with painful neuropathy,
      symptomatic and palliative measures are often effective. Stepwise addition of
      antidepressants to simple analgesics has proven to be effective in patients with
      troublesome pain. During recent years a class of drugs have been developed that
      inhibits the activation of the polyol pathway in diabetic nerves. These so-called
      aldose reductase inhibitors hold promise for a targeted treatment regimen in the
      near future. The aldose reductase inhibitors are already available in several
      European countries and in Japan.

PMID- 7711361
TI  - Nilvadipine. A review of its pharmacodynamic and pharmacokinetic properties,
      therapeutic use in hypertension and potential in cerebrovascular disease and
      angina.
AB  - Nilvadipine, a calcium antagonist of the dihydropyridine class, selectively
      blocks calcium channels in vascular smooth muscle. Compared with nifedipine, the
      prototype of the dihydropyridines, nilvadipine has a longer duration of action.
      The antihypertensive efficacy of nilvadipine appears to be comparable with that
      of nicardipine and nitrendipine, enalapril and captopril and
      hydrochlorothiazide/triamterene, although further clinical experience is required
      to establish the claimed advantages nilvadipine may have over the other
      dihydropyridine derivatives currently used to treat hypertension. Preliminary
      studies suggest that nilvadipine may also be useful in the treatment of patients
      with stable exertional or variant angina. Studies conducted in Japan indicate
      that nilvadipine improves symptoms resulting from cerebral infarction in some
      patients, but further comparative studies are required to confirm these results.
      The tolerability of nilvadipine appears to be comparable with that of nicardipine
      and better than that of nifedipine with respect to flushes, oedema and liver
      function abnormalities. As is typical of calcium antagonists, there is no
      evidence of tolerance to the antihypertensive effects of nilvadipine. The drug is
      equally effective in treating hypertension in elderly and younger patients and
      does not appear to adversely affect glucose or lipid metabolism. Thus, provided
      its apparently good tolerability is confirmed by wider clinical experience, it
      should be a suitable alternative to other calcium antagonists when used alone or
      in conjunction with other drugs for the majority of patients with mild to
      moderate hypertension.

PMID- 7711362
TI  - Should high lipid levels in very old patients be lowered?

PMID- 7711360
TI  - Changes in protein kinases in brain aging and Alzheimer's disease. Implications
      for drug therapy.
AB  - There is ample evidence for the involvement of aberrant protein phosphorylation
      reactions in aging and age-associated neurological disorders. Alzheimer's disease
      (AD) in particular. The exact nature of this involvement, however, is not yet
      elucidated. In the brain tissue of AD patients, there are numerous examples of
      altered protein phosphorylation pathways. Individual protein kinases and
      phosphorylation by these kinases in AD brain tissues have been found to be
      altered. Protein kinases studied include protein kinase C (PKC), protein tyrosine
      kinase (PTK), casein kinase II (CKII), Ca++/calmodulin-dependent kinase II and
      mitogen-activated protein (MAP) kinases, all of which are thought to be necessary
      for cell survival. Interestingly, different protein kinases are involved in
      different aspects of AD pathology. It is postulated that the perturbation of
      amyloid beta/A4-protein precursor (APP) metabolism triggers abnormal protein
      phosphorylation reactions responsible for dysfunction and eventual death of
      neurons in the brain. The association of APP mutation with certain familial types
      of AD strongly suggests that there might be a link between aberrant APP
      metabolism, protein phosphorylation cascades and the eventual expression of AD
      pathology (plaques and tangles) and neurodegeneration. In summary, recent studies
      emphasise the prime importance of protein phosphorylation in aging and AD. This
      raises the possibility that future pharmacological interventions might be devised
      to interfere with this kinase cascade for the prevention or treatment of age
      associated neurological disorders.

PMID- 7711364
TI  - Low back pain hospitalization in Washington State: recent trends and geographic
      variations.
AB  - For several years, interest in clinical practice patterns has increased due to
      concerns about the costs and quality of health care. Our objectives were to
      examine recent trends and geographic variations in low back pain hospitalization.
      We analyzed data from a Washington State automated database for 1987-1992. Low
      back surgery rates in Washington changed little during the study years. In
      contrast, nonsurgical hospitalization rates fell from 15.5 to 5.1 per 10,000. The
      proportion of operations involving fusion decreased from 15.8% in 1987 to 11.7%
      in 1990, and then remained stable. During 1990, important county-to-county
      variations were observed in surgery rates, nonsurgical hospitalization rates, the
      proportion of operations involving fusion, and the percentage of surgical
      patients undergoing reoperation within 3 years. Wide county variations suggest
      that there may be overutilization or underutilization of low back pain treatments
      in some geographic areas. A more consistent approach to the management of back
      problems may benefit patients.

PMID- 7711365
TI  - Asymmetry of lumbar lateral flexion and treatment outcome in chronic low-back
      pain patients.
AB  - In a study on the treatment of chronic low-back pain (n = 456 patients; 58% men,
      35-54 years of age), 3-month treatment outcome was assessed by back pain
      questionnaires and physical measurements including spinal and hip mobility and
      trunk muscle strength. Changes in differences between ranges of right and left
      lumbar lateral flexion and rotation of > 5 degrees from pretreatment to follow-up
      were recorded. A relative increase in left lumbar lateral flexion was associated
      with a better treatment outcome according to both back pain and physical
      performance (p < 0.05-0.001). With spinal rotation measurements no similar
      connections were observed. The results point to a connection between back pain
      and asymmetric spinal function, which may have pathogenetic and therapeutic
      significance.

PMID- 7711363
TI  - Pharmacological approaches to reduce perioperative transfusion requirements in
      the aged.
AB  - Although iron deficiency is undoubtedly the commonest cause of anaemia even in
      elderly people, the aetiology is not always clear owing to various underlying
      diseases. Correction of anaemia is sometimes needed before surgery. The use of
      drugs that may influence blood coagulation, such as aspirin (acetylsalicylic
      acid), should be checked. Perioperative allogenic blood transfusion can often be
      avoided by the use of autologous blood and improved surgical techniques.
      Autologous blood donations are preferable in cases of planned surgery. Epoetin
      (recombinant human erythropoietin) in combination with iron supplementation
      facilitates the donation of autologous blood, even in elderly patients. Another
      method of avoiding allogenic blood transfusion is the collection and reuse of the
      blood a patient sheds in operations. During and/or after surgery, many
      haemostatic agents are available. Moreover, recent developments in gene
      engineering have enabled the utilisation of recombinant cytokines and coagulation
      factors. Further work remains to be done to define the proper use of these
      agents.

PMID- 7711366
TI  - Diurnal variation in trunk kinematics during a typical work shift.
AB  - Diurnal variation in trunk flexibility, defined as changes in range of motion,
      has been previously observed and quantified. Prior studies have shown that
      decreased disk height occurs as the day progresses and allows the spinal
      ligaments to slacken, resulting in an increase in the range of motion
      (flexibility) and a possible reduction in the risk of injury. This risk may be
      accentuated under dynamic motions of the spine. This study was conducted to
      observe the change in dynamic trunk mobility as a function of time of the day.
      Trunk motions of 21 men were observed at three specific times of the day using a
      triaxial electrogoniometer. No variation in trunk range of motion in any of the
      cardinal planes was observed. However, velocity and acceleration in the sagittal
      plane showed significant variations, suggesting the reexamination of the "slack
      ligaments" hypothesis. This study asserts that identifying flexibility by only
      its static component, range of motion, gives only partial information about the
      diurnal variation experienced by the spine. Industrial injuries occurring in the
      early morning hours may be a result of insufficient trunk mobility. This study
      indicates that risk associated with diurnal variation is far more complex than
      originally thought.

PMID- 7711367
TI  - Pathoanatomical and radiographic findings in spinal breast cancer metastases.
AB  - Spine specimens infested with breast cancer metastases, ranging from localized
      seed of small tumor deposits to massive invasion and vertebral collapse, were
      frozen in situ, removed, examined with both conventional radiography and high
      resolution computed tomography (CT), and then studied in great detail by serial
      cryoplaning. The majority of metastases in the total of 53.5 vertebrae were
      lytic, and most were in close contact with the vertebral wall or the endplates.
      Depressions and defects of the endplates were associated with compensatory
      expansion of the intervertebral discs. Although lytic lesions abutting endplate
      defects had the radiological appearance of metastases, all contained herniated
      disc material rather than tumor. Only four of the 29 grossly destroyed and
      collapsed vertebrae showed extrusion of the posterior vertebral wall into the
      spinal canal. Tumor growth in the epidural space was rare. There were no
      macroscopical reactive changes of the osseoligamentous or neurovascular spinal
      elements to the metastases, but abnormalities of the posterior elements (kissing
      spines, facet joint subluxation, and pars interarticularis failure) were common.

PMID- 7711368
TI  - Dynamic canal encroachment during thoracolumbar burst fractures.
AB  - In the burst fractures seen clinically, often poor correlation exists between the
      neurological deficit and the canal encroachment measured on post-trauma
      radiographic images. The purpose of the present study was to determine whether
      the dynamic canal encroachment during the trauma is greater than the static canal
      encroachment posttrauma. We successfully produced burst fractures in nine of 15
      fresh human cadaveric thoracolumbar spine specimens (T11-L1). The specimens were
      incrementally impacted in a high-speed trauma apparatus until fracture occurred.
      During the trauma, dynamic canal encroachments were measured using three
      specially designed transducers placed in the canal at the levels of the superior
      end-plates of the T12 and L1 and the T12/L1 disk. After the trauma, residual
      static spinal canal encroachments were measured from the radiographs of the
      specimens that were prepared with 1.6-mm diameter steel balls lining the canal in
      the midsagittal plane. We found that the average canal diameter was 16.6 +/- 1.3
      mm and the static canal encroachment was 18.0% of the canal diameter. The
      corresponding dynamic canal encroachment was 33.3%. Thus, the dynamic canal
      encroachment was 85% more than the static measurement. The clinical significance
      of this study lies in providing awareness to the clinician that the dynamic canal
      encroachment is significantly greater than the static canal encroachment seen on
      posttrauma radiographs or computed tomography scans. The finding may also explain
      the clinical observation of poor correlation between the canal encroachment
      measured radiographically and the neurological deficit.

PMID- 7711369
TI  - Rotational stability of a spinal pedicle screw/rod system.
AB  - Although the geometry of spinal instrumentation constructs may significantly
      affect efficacy, the variation in biomechanical data may not assist the clinician
      in an appropriate selection. The purpose of the present study was to quantify the
      effects of transverse fixators on rotational strength of a common pedicle-screw
      with-rods system. Pedicle screws were mounted in blocks of polymethyl
      methacrylate at angles to reproduce the configuration of placement in the human
      lumbar spine. Twenty cycles of +/- 12 N-m axial rotation moment was applied, and
      the steady-state response was used in the analysis. Configurations tested
      included both medial and lateral placement of longitudinal rods as well as the
      addition of one or two transverse rods. Up to a 20% difference in stiffness was
      noted between medial and lateral placement of longitudinal rods when no
      transverse rods were mounted. A maximum difference in flexibility of 6% was noted
      between the use of one and two transverse rods. For medially placed rods, a
      single transverse connector will add significant rotational stiffness even for
      shorter rod lengths; for laterally placed longitudinal rods, only the longer rod
      lengths need a transverse connector.

PMID- 7711370
TI  - Biomechanical analysis of a new anterior spine implant for post-corpectomy
      instability.
AB  - Corpectomies in the lumbar and thoracic spine are sometimes necessary in the
      treatment of vertebral tumor, trauma, and degeneration. The resultant defect
      creates marked instability. Present methods to correct this problem involve
      spanning the defect with structural bone graft and applying either anterior or
      posterior instrumentation. Some investigators have designed vertebral
      replacements that distract and wedge into the corpectomy site. This study
      investigates a proposed prosthesis with a unique method of fixation: a vertebral
      replacement is fixed to the bodies above and below by screws that are oriented
      rostrally and caudally. This fixation prevents cantelever bending of the screws,
      migration of the implant, and possibly visceral damage by the placement of the
      device. This study investigates the biomechanical performance of this device in
      flexion, extension, and axial loading in a calf spine model. In comparison with
      normal spines, this device restored the biomechanical strength of the spine to at
      least normal levels in all planes tested. It appears that a device of this design
      may be useful for the reconstruction of vertebral diseases and may reduce the
      need for more extensive surgeries.

PMID- 7711371
TI  - Lumbar pedicle screw salvage: pullout testing of three different pedicle screw
      designs.
AB  - Although research has determined pedicle screw pullout strengths for normal and
      osteoporotic bone, this study provides the first biomechanical analysis of
      pedicle screw salvage. Ten fresh frozen human lumbar spines were separated into
      individual vertebrae; 6.0 x 40 mm pedicle screws were placed in each pedicle; and
      an axial pullout test was performed to establish control values. Ultimate load,
      initial stiffness, work, and displacement data were calculated. Each vertebra was
      reinstrumented with one 7.0 x 40 mm variable screw placement (VSP) screw side by
      side with either a 7.0 mm Cotrel Dubousset sacral screw (CD) or a 7.0 mm Compact
      Cotrel Dubousset pedicle screw (CCD). Pullout tests were repeated and compared to
      control data for individual screws and for each VSP/CD or VSP/CCD pair. Vertebrae
      were then reinstrumented with 8.0 mm VSP and CD screws and paired pullouts
      repeated. Statistical analysis was carried out using a paired T test. Analysis of
      intravertebral and intergroup variation of controls was carried out using a
      Paired Two Sample T test. The 7.0 mm CCD screws restored pullout strength to 62%
      of control pullouts; 7.0 mm CD screws, to 85%; 7.0 mm VSP screws, to 99%; 8.0 mm
      CD screws, to 109%; and 8.0 mm VSP screws, to 148% of control pullouts. The 7.0
      mm VSP salvage screws exceeded CD screws in ultimate load by 22.5% (p < .03) and
      CCD screws by 33.5% (p < .05). The 8.0 mm salvage screws significantly increased
      pullout relative to both controls and all 7.0 mm salvage screws, with 8.0 mm VSP
      exceeding 8.0 mm CD by 34% (p < .03). Initial stiffness was also significantly
      greater in VSP than CD screws. Although applied in a smaller number of vertebrae,
      8.0 mm screws sufficiently outperformed smaller screws to provide statistically
      significant differences. The 7.0 mm VSP salvage screws restored pullout to
      control levels, roughly equivalent to outcomes previously obtained with
      unpressurized polymethylmethacrylate (PMMA).

PMID- 7711372
TI  - A modified posterolateral approach to the thoracic spine.
AB  - We describe a modified technique for posterolateral approach to the thoracic
      spine and report the use of this procedure in 21 patients. The technique is safe
      and effective for selected indications. The evolution of the posterolateral or
      costotransversectomy approach to the thoracic spine has in large part focused on
      enlarging the exposure to the vertebral bodies and epidural space by resecting an
      increasing number of ribs and removing a wider portion of those ribs resected. In
      this modified approach to the thoracic spine, the costovertebral articulation is
      preserved, and no rib resection is necessary to gain adequate exposure to the
      thoracic vertebral body and epidural space. We did a retrospective review of 21
      patients undergoing 22 modified posterolateral approaches to the thoracic spine.
      Sixteen patients had biopsies of thoracic vertebral lesions through this
      approach; 3 underwent decompression of the thoracic spinal cord; 2 approaches
      were done for the removal of a herniated thoracic disc; and in one, the pedicle
      was removed. This modified posterolateral approach allowed adequate exposure for
      selected indications. One complication, a wound infection, developed after biopsy
      for suspected osteomyelitis. This modified posterolateral approach is well suited
      to provide access for biopsy of thoracic spinal lesions; for decompression of a
      paraspinal abscess; and for decompression of the thoracic spinal cord by
      anterolateral compressive lesions such as herniated thoracic disc or epidural
      tumor when resection of the vertebral body is not necessary; or the approach may
      be used for patients who are debilitated or at poor risk to undergo thoracotomy.

PMID- 7711373
TI  - The use of MRI-compatible titanium segmental spinal instrumentation in pediatric
      patients with intraspinal tumor.
AB  - Severe kyphosis is a frequent complication of multiple laminectomies for the
      treatment of intraspinal tumors in growing children. Early Segmental Spinal
      Instrumentation (SSI) and posterior spinal fusion can prevent this complication,
      but because of ferromagnetic properties of conventional stainless steel implants,
      magnetic resonance imaging (MRI) performed to determine completeness of the
      resection and later for recurrence of the tumor becomes difficult. To overcome
      the problems with postoperative imaging, we have resorted to early stabilization
      of the spine following laminectomy with titanium alloy implants. The decreased
      ferromagnetic properties of titanium alloy result in less scatter distortion of
      the image, thus permitting a better follow-up of the tumor. This paper reports
      five consecutive patients with stabilization of the spine with titanium alloy
      implants and posterior spinal fusion done at the time of laminectomy. The use of
      titanium alloy implants in these patients allowed detailed MRI follow-up in all
      cases, and in two patients offered the surgical team information that altered or
      affected the patient's care.

PMID- 7711374
TI  - Dorsal ramus irritation associated with recurrent low back pain and its relief
      with local anesthetic or training therapy.
AB  - Nerves leave the spinal cord as mainly motor primary rootlets and sensory
      rootlets. These join to nerve root before leaving the spinal canal. After the
      root canal, the nerve root branches into the ventral root, which contains sensory
      and motor fibers innervating the extremities, and the dorsal root, that is, the
      dorsal ramus, which innervates the posterior structures, for example, back
      muscles: the dorsal ramus itself may become irritated (dorsal ramus syndrome).
      Especially predisposed to entrapment is the medial branch of the dorsal ramus,
      which innervates the multifidus muscle and also contains pain fibers. Here we
      describe the influence of local anesthesia and back-muscle-training therapy on
      subjective and objective pain parameters in 21 low-back-pain patients who had
      similar clinical status and neurophysiologic findings and whose recurrent low
      back pain was most apparently associated with dorsal ramus neuropathy, without
      any radiologic or neurophysiologic evidence of more proximal ventral nerve root
      damage in the spinal cord or at the nerve root origin. After treatment, all were
      pain free and back muscle activity during lumbar-pelvic rhythm was normalized.

PMID- 7711375
TI  - Intraspinal extradural ganglion cyst.
AB  - Occurrence of ganglion cysts in the spine is extremely rare. Common symptoms
      include intermittent lumbar pain and pain at night. Neurological examination to
      distinguish from other etiologies of radicular pain may be difficult. The L4-L5
      level is the most common sight of occurrence. Radiographically, degenerative
      changes, particularly spondylolisthesis, are a common finding. MRI appearance of
      the cysts is variable, according to the composition of the cyst. A ganglion cyst
      should be considered in the differential of radicular pain in the presence of
      degenerative changes of the lumbar spine.

PMID- 7711376
TI  - Intraradicular disc herniation: a case report and review of the literature.
AB  - Intradural disc herniation accounts for < 0.3% of all disc herniations.
      Intraradicular disc herniation accounts for 4.1% of all such cases. Preoperative
      diagnosis is difficult, and a high index of suspicion during surgery is required
      for the diagnosis. We present a patient with intraradicular disc herniation in
      the lumbar region whose symptoms were severe enough to recommend surgery. The
      myelogram showed a block at the involved nerve root. Diagnosis of intraradicular
      herniation was made during surgery. The symptoms were immediately relieved by
      surgery. The literature on intradural and intraradicular disc herniation is
      reviewed.

PMID- 7711377
TI  - Neurogenic bladder and nerve root cysts.

PMID- 7711378
TI  - Regulation of oocyte donation to women over the age of 50: a question of
      reproductive choice.

PMID- 7711379
TI  - Infertility treatment in Poland.

PMID- 7711380
TI  - Does patient semen quality alter during an in vitro fertilization (IVF) program
      in a manner that is clinically significant when specific counseling is in
      operation?
AB  - PURPOSE: It has been shown that the stress of infertility may impair semen
      quality. Whether counseling can attenuate this affect is unproven. This study
      examines, in an IVF program setting, where specific counseling is in operation,
      whether semen collected on the day of oocyte recovery is significantly different
      from that obtained during the prior clinical suitability assessment of the
      couple. RESULTS: In the 125 consecutive couples examined, there were no
      significant overall differences in semen volume or sperm density. There was a
      significant increase in sperm motility on the day of oocyte retrieval (P <
      0.001). Twenty-three patients (18.4%) showed an increase in quality, and 21
      (16.8%) a decrease, on the day of oocyte recovery. The environment of production
      appeared to exert no influence. Fertilization failure occurred in seven couples,
      three (14%) of whom presented for the first time with decreased semen parameters
      on the day of IVF. This compares with 1 of 23 (4%) fertilization failure in those
      whose parameters increased. CONCLUSION: The semen quality of the vast majority of
      the patients studied in this highly counseled program does not appear to be
      significantly affected by the superstress of participation in the day of oocyte
      recovery.

PMID- 7711381
TI  - Direct intraperitoneal insemination and controlled ovarian hyperstimulation in
      subfertile couples.
AB  - METHOD: We performed direct intraperitoneal insemination in combination with
      superovulation and washed husband's spermatozoa as the treatment of infertility
      caused by oligospermia, cervical subfertility, or ovulatory dysfunction or
      idiopathic infertility in 162 couples during 360 cycles. RESULTS: The pregnancy
      rate per couple was 21.9% in the cervical-factor group, 20.9% in the idiopathic
      group, 4.9% in the oligospermia group, and 15.5% in the ovulatory dysfunction
      group. CONCLUSION: The pregnancy rate was 33.3% for all couples and 15.0% for all
      cycles.

PMID- 7711382
TI  - Interleukin-1 beta, interleukin-6, and growth hormone levels in human follicular
      fluid.
AB  - PURPOSE: To investigate possible relationships of interleukin-1 beta (IL-1 beta),
      interleukin-6 (IL-6), and growth hormone (GH) with biochemical variables in human
      follicular fluid (FF) and selected in vitro fertilization (IVF) parameters.
      METHODS: A total of 67 FF samples (n = 67 patients undergoing oocyte retrieval
      for IVF) was evaluated. IL-1 beta, IL-6, GH, hLH, FSH, PRL, hCG, testosterone,
      total protein, fibrinogen, sialic acid, alpha 1-antitrypsin, plasminogen levels,
      and spectrophotometric absorbance at 458 nm were analyzed for selected FF. IL-6
      and GH levels of serum and FF samples were also compared (n = 23). RESULTS:
      Immunoreactive levels of IL-1 beta, IL-6, and GH were detected in all FF samples.
      A positive correlation existed for IL-6 (r = 0.5069, P = 0.0161) when serum-to-FF
      levels were compared (concentration ratio, 1:1.857). Smaller-volume follicles (<
      4 ml) were associated with high IL-1 beta levels (P = 0.0229), and an additional
      tendency of IL-1 beta to decrease with increasing embryo cleavage and scoring was
      observed. With the exception of a weak positive correlation between follicular IL
      1 beta and testosterone levels (r = 0.3128, P = 0.025), no other relationship
      with biochemical variables or IVF parameters (etiology, e.g., endometriosis)
      could be implicated. CONCLUSIONS: Substantially higher IL-6 levels occurred in FF
      compared to serum, thus supporting intrafollicular production. Interleukin-1
      beta, IL-6, and GH levels in FF are, however, unsuitable markers for in vitro
      fertilization outcome.

PMID- 7711383
TI  - Alpha-minimum essential medium (MEM) enhances in vitro hatched blastocyst
      development and cell number per embryo over Ham's F-10.
AB  - PROBLEM: The development of mouse embryos in vitro is affected primarily by mouse
      strain-genotype and culture conditions. Embryo culture studies evaluate the
      effectiveness of culture conditions in supporting one- or two-cell mouse embryo
      development to the blastocyst stage by reporting the percentage blastocyst
      formation rate. METHOD: Determining the cell number per cultured blastocyst may
      also help in determining embryo culture medium quality. The objective of this
      study was to determine the effect of MEM and Ham's F-10 on overall CFW mouse
      embryo development and hatched blastocyst cell number in vitro. CFW embryos
      cultured in MEM had significantly higher (87%; P < 0.001) hatched blastocyst
      rates than embryos cultured in F-10 (56%). RESULTS: A significant difference in
      nuclei per hatched blastocyst was found between MEM and F-10 (P < 0.001). The
      results demonstrate that inbred mouse embryos have significantly higher
      blastocyst hatching rates and higher cell numbers per blastocyst when cultured in
      MEM.

PMID- 7711384
TI  - Endometrial secretory proteins enhance early embryo development.
AB  - PURPOSE: To evaluate the role of endometrial stromal cells and their secretory
      proteins in early embryo development, two-celled CB6F1 mouse embryos were
      cultured alone or cocultured with human endometrial stromal cells in various
      culture conditions. RESULTS: The percentage of embryo blastocyst formation,
      hatching, and outgrowth was significantly greater in (1) coculture with
      endometrial stromal cells than in a cell-free control when both coculture and
      control were carried out in protein-free medium or in RPMI 1640 plus 10% fetal
      calf serum; (2) coculture with hormone (i.e., progesterone plus relaxin)-treated
      cells than in coculture with hormone-nontreated cells; and (3) media supplemented
      with isolated endometrial secretory proteins than in media supplemented with BSA
      (0.35%). Embryo development was not found to be significantly different in
      coculture and in media supplemented with endometrial secretory protein.
      CONCLUSION: Our data provides credence to the theory that endometrial stromal
      cells enhance embryo development by secreting specific proteins that are
      beneficial to embryo growth in vitro.

PMID- 7711385
TI  - The use of the stem pessary to facilitate transcervical embryo transfer in women
      with cervical stenosis.

PMID- 7711386
TI  - Sperm donation and practice of AID in France.

PMID- 7711387
TI  - Preimplantation diagnosis of genetic and chromosomal disorders.

PMID- 7711388
TI  - Review: borders, patterns, and distinctive families of homeodomains.
AB  - PURPOSE: Homeotic proteins function as transcription factors in early
      embryogenesis of many organisms. To date, hundreds of distinctive homeoproteins
      have been identified, including 84 human homeodomains. However further progress
      in understanding functional relationships between particular homeoproteins and
      other embryonic regulators requires a comprehensive structural classification of
      these proteins. RESULTS: The most probable borders and conservative amino acid
      positions inside the homeodomain region have been established using a statistical
      analysis of variabilities of amino acid occurrences at various positions outside
      and inside the domain. A new format for a homeodomain sequence presentation and
      regular amino acid patterns which are strongly representative of distinctive
      homeodomain groups are proposed. Using the established patterns, 33 families of
      closely related homeodomains have been distinguished and classified. The total
      list of 297 homeodomain amino acid sequences is presented in the Appendix.
      CONCLUSION: The structural classification of homeodomains has been proposed. It
      can be useful for both the identification (or prediction) of new homeotic
      genes/proteins and the recognition of possible PCR-induced sequence errors. This
      systematics will also have an impact on understanding functional relationships
      among homeotic proteins and other genetic regulators of developmental processes.

PMID- 7711390
TI  - A pilot study of gonadotrophin releasing hormone agonist
      (GnRHa)/superovulation/donor intrauterine insemination (IUI) after unsuccessful
      artificial insemination with donor sperm (DI).

PMID- 7711389
TI  - Use of coculture with cumulus cells in insemination medium in human in vitro
      fertilization (IVF).
AB  - PURPOSE: In an initial trial, 16 of 33 (48%) bipronuclear human zygotes left in
      culture in the insemination drop from which they had originated developed to
      fully expanded blastocysts. RESULTS: This method was subsequently used for all
      supernumerary embryos judged unsuitable for replacement or cryopreservation on
      Day 1, 2, or 3 of development. Over a 4-year period, embryos reaching the fully
      expanded blastocyst stage were cryopreserved. Of 113 such blastocysts thawed, 81
      survived (72%), and upon transfer to 52 patients, 8 clinical pregnancies were
      established (15%), of which 6 were live births. Subsequently, following
      modification of some culture parameters, 60 patients had 296 supernumerary
      embryos cultured for 6 days; 43 of these patients (72%) had 148 embryos (50%)
      that cavitated and 134 (45%) of these cavitating embryos were judged to be fully
      expanded blastocycts; 125 (42%) of these embryos were cryopreserved. CONCLUSION:
      The blastocyst formation rate is similar to that reported by others using
      conventional culture procedures or coculture on Vero or other cell types. I
      conclude that cumulus cells are a ready source of feeder cells for the coculture
      of human embryos.

PMID- 7711391
TI  - The effect on sperm motility of probe covers used for transvaginal sonography.

PMID- 7711392
TI  - Standards of care.

PMID- 7711393
TI  - Evaluation of a home-based rehabilitation programme for patients recovering from
      acute myocardial infarction.
AB  - There is substantial evidence of the importance of rehabilitation for patients
      recovering from acute myocardial infarction in reducing mortality, morbidity, and
      psychological distress. The aim of this study was to compare a recently
      established home-based coronary rehabilitation programme in a coronary care unit
      (CCU) with the provision of a selection of information leaflets commonly provided
      for patients after their myocardial infarction. A comparative study was carried
      out between two randomly allocated groups of patients receiving either the Heart
      Manual rehabilitation programme (n = 17) or general advice and information
      booklets (n = 17), with follow-up at 1, 3 and 6 weeks after discharge for both
      groups. Questionnaire measurements included anxiety and depression (HAD score),
      general practitioner (GP) visits, and patients' perception of their confidence of
      recovery and progress. The findings show that patients receiving the Heart Manual
      had significantly higher scores in their confidence of recovery and perception of
      their progress than the group receiving booklets. The Heart Manual group showed
      improved levels of anxiety with unchanged scores in depression, while patients
      receiving the booklets experienced increased depression with little change in
      their anxiety levels. These results help to provide guidance for health care
      professionals on a form of rehabilitation which is effective for patients and
      their families in hospital and within the community.

PMID- 7711394
TI  - Challenges for the future: the nurse's role in weaning patients from mechanical
      ventilation.
AB  - Weaning patients from mechanical ventilation and extubating them following
      cardiothoracic surgery has traditionally been the responsibility of medical
      staff. Within critical care settings some nurses, with the appropriate
      experience, actively take part in this process under the direction of an
      anaesthetist. In the Adult Intensive Care Unit (AICU) of Royal Brompton Hospital,
      a policy was developed to enable nurses to wean and extubate postoperative
      patients without the need for consultation with anaesthetic staff. It was
      envisaged that following the implementation of the policy other areas for nursing
      development and research would be highlighted. Issues relating to accountability,
      quality and practice are discussed.

PMID- 7711395
TI  - Paediatric pain assessment in intensive care units.
AB  - In this exploration of the problem of assessing children' pain in intensive care
      units (ICUs), literature spanning the last 10 years was reviewed to identify
      factors that affect pain assessment, such as developmental stage, health
      professionals' attitudes and myths. Selected pain assessment tools are briefly
      described and evaluated for use in intensive care with children. Although this
      review is small, it is clear that despite nurses' recognition of the need for
      pain assessment in children, and the appearance of many new assessment tools,
      health professionals may still not be managing paediatric pain effectively. The
      search also revealed that little appears to have been written about this problem
      as it occurs in ICUs, and more research is indicated.

PMID- 7711396
TI  - The sedation of patients in intensive care units: a nursing review.
AB  - The aim of maintaining optimal levels of sedation in critically ill patients is
      an important concern of intensive care nurses. In addition, the specific
      requirements of patients are individual and will vary according to the severity
      of their illness and/or supportive treatment that they may be undergoing
      (Hopkinson & Freeman 1988). The use of sedation in an intensive care unit (ICU)
      is therefore a complex nursing issue. The purpose of this literature review is to
      evaluate the need for ensuring that patients are receiving appropriate sedation
      whilst in an ICU. This is followed by consideration of what is meant by optimal
      levels of sedation, a review of past and current sedation practice and the
      importance of nurses assessing the depth of sedation of the critically ill
      patients within their care. Key points are raised, with recommendations for
      future nursing practice.

PMID- 7711397
TI  - Ethical dilemmas in intensive care--a case history.
AB  - The decision either to withdraw or to continue treating a patient, may often be
      the source of both ethical and moral dilemmas for the health care professionals
      involved in that decision. Within the context of an intensive care environment
      these issues become even more significant as the patient's quality of life is
      determined by another individual. This case study reviews both the ethical
      principles that are involved in the decision making process, and the measurement
      of an individual's quality of life. By focusing on two patients in different
      situations the ethical problems that nurses face in intensive care are
      highlighted.

PMID- 7711398
TI  - Ethics in paediatric intensive care.
AB  - Although many nurses may not consciously acknowledge the fact, ethical
      considerations are a vital part of nursing practice. The concept and definition
      of ethics, and how these may be applied to Paediatric Intensive Care in
      particular are considered here. Suggested frameworks for addressing ethical
      dilemmas are examined, as well as the possible conflict between ethics and the
      law.

PMID- 7711399
TI  - Near drowning.
AB  - Irrespective of the immersion medium, the primary consequence of any near
      drowning episode is hypoxemia and resultant hypoxia. The gravest consequence of
      hypoxia is cerebral insult. A major contributor to cerebral recovery in cold
      water drowning is hypothermia and resultant cerebral hypometabolism. Though the
      causal mechanism of this phenomenon is the focus of debate, hypothermia at
      presentation remains a good prognostic indicator. Nursing and medical care should
      be directed towards reversal of hypoxemia and cerebral salvage with this factor
      in mind, rather than expectation of relatively rare sequelae. This article
      reviews the pathophysiology of near drowning and contemporary trends in its
      treatment.

PMID- 7711401
TI  - "Where are you going, neonatal medicine?".

PMID- 7711400
TI  - Pressure sores--a ticking time-bomb.
AB  - Health Service managers and administrators increasingly find themselves under
      fire for intruding on what have traditionally been regarded as clinical or
      nursing decisions as demands increase for more efficiency and cost cutting,
      particularly in hospital care. Now there is a new turn of the screw. It appears
      that pressures sores, frequently given low priority despite being potential
      killer, are revealed to be a time-bomb ticking away under the bedclothes. Indeed,
      the estimated 2000 deaths a year in the UK attributed to pressure sores suggest
      that conventional hospital beds and mattresses should carry a health warning!

PMID- 7711402
TI  - What is advanced practice?

PMID- 7711403
TI  - Ecstasy overdose: a case study.

PMID- 7711404
TI  - Kidney transplantation in hepatitis B surface antigen carriers.
AB  - Chronic hepatitis B surface antigen (HBsAg) carriers run a high risk of
      developing chronic liver disease after renal transplantation. To determine the
      impact of liver disease on long-term morbidity and mortality of HBsAg carriers
      following kidney transplantation we analyzed 1977 patients, including 76 HBsAg
      carriers, who underwent renal transplantation during the period 1968-1992.
      Although the HBsAg carriers had a better 5-year patient and graft survival rate
      (94% and 83%) than HBsAg-negative patients (87% and 61%), the prognosis was poor
      after the tenth year of transplantation. Transplant loss is more frequently
      caused by death of the HBsAg carriers, in contrast to the total population (34%
      vs 17% for HBsAg-negative patients). Death occurs in 73% of cases due to
      complications of hepatitis B. In the HBsAg-negative patients, the predominant
      cause of death is cardiovascular failure (51% vs 11% in HBsAg carriers), whereas
      only 2% died of liver disease. Kidney transplantation in HBsAg carriers with
      normal liver function appears to be justified because of rare graft loss due to
      acute rejection, low early morbidity and mortality, and late onset of fatal
      hepatic deterioration.

PMID- 7711405
TI  - Serum amyloid A protein (SAA): a marker for liver allograft rejection in humans.
AB  - Serum amyloid A protein (SAA) concentrations were monitored in 12 consecutive
      liver transplant recipients until the 70th postoperative day. Fourteen rejection
      episodes were identified histologically in 42 liver biopsies of the grafts. Of 12
      rejections 8 (66.7%) were characterized by pronounced simultaneous increases in
      SAA concentrations in plasma, the mean peak value being 16.94 +/- 8.82 mg/dl
      (range 4.58-28.55 mg/dl) compared with a mean normal value of 0.98 +/- 0.42 mg/dl
      in healthy controls. Of 42 biopsies 28 did not show histological evidence of
      graft rejection. Of 25 negative biopsies 24 (96.0%) were not accompanied by a
      parallel SAA increase in plasma. These findings demonstrate that measurements of
      SAA concentrations may provide a valuable noninvasive aid in identifying acute
      liver allograft rejection in humans.

PMID- 7711407
TI  - Development of resistance by Enterobacter cloacae during therapy of pulmonary
      infections in intensive care patients.
AB  - The emergence of resistance during therapy and the efficacy of different
      antibiotic therapy regimens were studied in 38 intensive care patients suffering
      from pulmonary infections caused by Enterobacter cloacae. Every three days a
      fresh isolate was obtained from each patient and tested in vitro for
      susceptibility to 16 antibiotics by determination of the minimal inhibitory
      concentrations. During therapy with cefotaxime and tobramycin the E. cloacae
      strains from 47% of the patients became resistant to cefotaxime within 6 days. In
      all cases resistance encompassed all other broad-spectrum penicillins and
      cephalosporins tested, as well as aztreonam. Development of resistance regularly
      led to persistence of bacteria. Resistance to tobramycin, ciprofloxacin or
      imipenem was not observed. Treatment of 25 patients with persisting E. cloacae
      infections was successful in 17 out of 18 patients treated with imipenem and in 6
      out of 7 patients receiving ciprofloxacin.

PMID- 7711406
TI  - Urinary zinc excretion and acute phase response in cancer patients.
AB  - We investigated urinary zinc and serum levels of C-reactive protein, alpha-1 acid
      glycoprotein, haptoglobin, transferrin and prealbumin in 55 patients with solid
      tumors and 20 controls. Urinary zinc, serum C-reactive protein, alpha-1 acid
      glycoprotein and haptoglobin were significantly higher, and serum prealbumin was
      significantly lower in cancer patients. A significant positive correlation
      between urinary zinc and C-reactive protein, alpha-1 acid glycoprotein and
      haptoglobin, as well as a negative correlation with transferrin and prealbumin
      were observed. Hyperzincuria in cancer patients appears to be linked to the acute
      phase response. Our data provide further evidence implicating systemic
      inflammatory response in increased urinary zinc excretion.

PMID- 7711408
TI  - Elevation of intracranial pressure in acute AIDS-related cryptococcal meningitis.
AB  - Prior to the AIDS-era, elevation of intracranial pressure was known to be a
      typical complication of cryptococcal meningitis associated with an increased risk
      of early death. In AIDS-patients, however, the prevalence and clinical
      significance of this complication are as yet unclear. We analysed clinical
      features and courses, CSF findings, serological results and neuroimaging scans in
      acute cryptococcal meningitis in eight patients with AIDS. Five showed symptoms
      and signs compatible with raised intracranial pressure, which was life
      threatening in one and the most probable cause of death in another. Serial
      monitoring of intracranial pressure together with repeated CSF analysis revealed
      that severe intracranial pressure elevation in AIDS related cryptococcal
      meningitis can occur in spite of effective antimycotic treatment, does not depend
      on an increased CSF/serum osmolality ratio or CSF overproduction and can be
      associated with normal cranial computed tomography and magnetic resonance imaging
      findings. Our data support the hypothesis that CSF reabsorption failure plays the
      crucial role in the pathophysiological mechanism. External lumbar drainage may be
      of benefit in selected cases of acute AIDS related cryptococcal meningitis with
      persisting life threatening elevation in intracranial pressure and normal
      computed tomogram.

PMID- 7711409
TI  - Insulin-dependent diabetes mellitus following pentamidine therapy in a patient
      with AIDS.
AB  - Pentamidine is known to cause severe dysglycaemia by damaging beta-cell function
      of the pancreas. The exact mechanism still remains unclear. We report the case of
      a 53-year-old man infected with the human immunodeficiency virus who developed
      insulin-dependent permanent diabetes mellitus 3 days after starting intravenous
      treatment with pentamidine for pneumocystis carinii pneumonia. Discharged from
      hospital the daily need of insulin increased continuously over one year now
      requiring an average dose of 80 units per day. So far, a number of cases of
      insulin-dependent diabetes mellitus following pentamidine therapy has been
      reported, but long-term observations are rare.

PMID- 7711410
TI  - Sustained elimination of hepatitis B virus from serum induced in a patient with
      chronic hepatitis B and advanced human immunodeficiency virus infection.
AB  - A 48-year-old male patient was admitted with acquired immunodeficiency syndrome
      (stage III, Centers for Disease Control 1993) and viremic hepatitis B. Blood CD4
      count was 15/microliters. Discontinuation of prednisolone, previously prescribed
      by the patient's family practitioner because of elevated liver enzymes, resulted
      in severe hepatitis (alanine aminotransferase > 300U/l). Administration of
      interferon-alpha (9 x 10(6) U s.c. 3 x weekly) was initiated. Serum markers of
      viral replication disappeared, and aminotransferase levels returned to normal
      within a few weeks. The patient's serum was found negative for HBsAg after 3
      months. Immunohistochemical analysis of liver biopsies before and during
      interferon therapy showed disappearance of all hepatitis B virus antigens and a
      marked reduction in inflammatory activity. Hepatitis B virus seroconversion
      remained stable until the patient died from the syndrome 2 years later. This case
      shows that in spite of severe HIV-associated immune deficiency with CD4 counts
      constantly below 100/microliters, interferon-alpha can lead to sustained
      serological and histological improvement of viremic hepatitis B. Previous
      administration and discontinuation of cortisone may have helped to reach this
      effect.

PMID- 7711411
TI  - Pneumococcal parotitis and cervical lymph node abscesses in an HIV-infected
      patient.
AB  - The case of a 33-year-old patient with rapid onset of bilateral parotid gland and
      lymph node abscesses is described. The patient was positive for human
      immunodeficiency virus 1 and presented with a history of interstitial lymphocytic
      pneumonia and pneumococcal meningitis prior to admission. The patient received
      cotrimoxazole as primary prophylaxis against Pneumocystis carinii pneumonia. Fine
      needle aspiration from the abscesses yielded Streptococcus pneumoniae. Penicillin
      G treatment in combination with surgical drainage of the lesions led to healing
      with minimal residual lymph node enlargement. No relapse was noted until 12
      months after presentation.

PMID- 7711412
TI  - Treatment of atypical leishmaniasis with interferon gamma resulting in
      progression of Kaposi's sarcoma in an AIDS patient.
AB  - Visceral leishmaniasis (kala-azar) affecting HIV-infected patient is being
      reported in increasing frequency. A 40-year-old German bisexual patient with full
      blown AIDS is described who presented with Kaposi's sarcoma, epigastric pain,
      diarrhea, and weight loss but without fever. Leishmania amastigotes were
      initially found in biopsies from stomach, duodenum, and a cutaneous Kaposi's
      sarcoma lesion but were later also recovered from bone marrow and lymph node. The
      patient received three courses of a combination of pentavalent antimony and
      interferon-gamma. In addition to the common side effects such as fever,
      thrombocytopenia, and elevated amylase and lipase, a vivid progression of the
      Kaposi's sarcoma was noted. Tumor progression was temporally closely associated
      with treatment with interferon-gamma. Because this phenomenon has also been
      observed in other patients, we advise caution when using interferon-gamma in
      patients with Kaposi's sarcoma.

PMID- 7711413
TI  - Cryoglobulinemia: a complication of infectious disease.
AB  - We report on a 23-year-old male patient with general weakness, subfebrile
      temperatures, and arthralgia. The first symptoms were observed some months after
      a severe cytomegalovirus mononucleosis-gastroenteritis. High titers of
      cryoglobulins suggested an autoimmunological process. This case is interesting
      because of the association between cytomegalovirus infection and
      cryoglobulinemia. In conclusion, the differential diagnosis of autoimmune disease
      should be considered in the course of viral infections.

PMID- 7711414
TI  - A case of pure red cell aplasia: follow-up on different immunosuppressive
      regimens.
AB  - A 66-year-old patient was admitted to our hospital in January 1992 for further
      evaluation of severe normocytic anemia. Hemoglobin (Hb) was 3.5 g/dl,
      reticulocyte count 1%. Bone marrow showed a nearly complete lack of red cell
      precursors, thus favoring the diagnosis of acquired pure red cell aplasia (PRCA).
      Immunosuppressive therapy with prednisolone was started but had to be
      supplemented with azathioprine because of a further rapid decrease in Hb to 3.7
      g/dl after an initial transfusion of 6 U red blood cells. However, with this
      regimen a renewed decrease in Hb to 6.6 g/dl was noted, and further transfusions
      were required. Therefore therapy was switched to cyclosporine A (CyA) while
      tapering off prednisolone. Four months after the initial diagnosis a positive
      parvovirus B19 IgM antibody was found. After the failure of hematological
      remission with three immunosuppressive regimens a course of high-dose intravenous
      immunoglobulins (IVIG) was administered in July 1992. Six weeks after IVIG
      therapy a peak hemoglobin concentration of 12.3 g/dl was noted, and further
      transfusion was not required. CyA was tapered off in October 1992. One month
      later CyA was reinstituted because of a relapse of PRCA but was unsuccessful
      until January 1993. At this time immunosuppressive CyA therapy was discontinued
      because of a periodontal abscess. In February 1993 a second IVIG infusion was
      given, and a second remission of PRCA was noted, showing an increase in
      hemoglobin up to 14.5 g/dl by November 1993. At the last follow-up visit in
      February 1994 our patient was still in complete hematological remission.

PMID- 7711415
TI  - Cauda equina syndrome with multiple lumbar diverticula complicating long-standing
      ankylosing spondylitis.
AB  - A patient with cauda equina syndrome complicating long-standing inactive
      ankylosing spondylitis is described. The first neurological symptoms started 15
      years after the onset of ankylosing spondylitis. Over a follow-up period of 12
      years the cauda equina syndrome showed a slowly progressive but disabling course
      leading to sensory disturbances in the lumbar and sacral dermatomes, weakness and
      wasting of the muscles innervated by these nerve roots, sphincter disturbances,
      and impotence. Magnetic resonance imaging, computed tomography, and lumbar
      myelography showed enlargement of the dural sac with multiple lubar diverticula
      eroding the lumbosacral vertebrae. The pathophysiology of the cauda equina
      syndrome in ankylosing spondylitis is unclear. Surgical treatment seems justified
      only in patients with a short history of neurological symptoms.

PMID- 7711416
TI  - Two cases of neurological manifestations in eosinophilia: variations of one
      disease?
AB  - The hypereosinophilic syndrome is characterized by a long-lasting increase in
      circulating eosinophils in the absence of a definable etiology and by
      manifestations of multisystem involvement. It must be differentiated from the
      eosinophilia-myalgia syndrome related to the ingestion of L-tryptophan, although
      the clinical features may be similar. Two patients with hypereosinophilia not
      related to L-tryptophan intake are described who both became clinically
      symptomatic with neurological manifestations of acute and subacute onset: one
      with eosinophilic fasciitis and the other with painful polyneuropathy. Both
      responded well to corticosteroids.

PMID- 7711417
TI  - Treatment of patients with familial defective apolipoprotein B-100 with
      pravastatin and gemfibrozil: a two-period cross-over study.
AB  - Thirty patients with familial defective apolipoprotein B-100 were treated in a
      two-period (8 weeks each) cross-over study with pravastatin and gemfibrozil.
      Cholesterol, LDL cholesterol, and apo B were reduced by 20-25% (P < 10(-4)) by
      pravastatin and by 4-6% by gemfibrozil (pravastatin vs. gemfibrozil: P < 10(-4)).
      Response to pravastatin was variable and not correlated to gender, age, or apo E
      genotype. Gemfibrozil lowered triglycerides by 25% (P < 10(-4)) and raised HDL
      cholesterol by 11%. The effects of pravastatin on these two interrelated
      variables were significantly smaller. Both drugs increased Lp(a) significantly by
      about 10%. The LDL cholesterol lowering effect of pravastatin in patients with
      FDB is similar to that observed in patients with familial hypercholesterolemia.

PMID- 7711418
TI  - Interaction of allopurinol and hydrochlorothiazide during prolonged oral
      administration of both drugs in normal subjects. I. Uric acid kinetics.
AB  - The interaction of allopurinol (300 mg/day) and hydrochlorothiazide (50 mg/day)
      was studied in seven healthy male volunteers during prolonged coadministration of
      the two drugs using defined dietary conditions. A formula diet was administered
      with the allopurinol throughout the 24-day study, while hydrochlorothiazide was
      added during days 11-21. After the addition of hydrochlorothiazide both plasma
      uric acid and plasma oxipurinol rose for 6 days--24% and 30%, respectively,
      compared to steady-state levels during allopurinol alone (P < 0.01 each). In
      neither substance were variations in renal excretion significant. By the end of
      combined treatment (day 21), the changes induced by hydrochlorothiazide had
      already been reversed to a considerable extent. It is concluded that both in
      normal individuals and in patients with normal renal clearance of uric acid the
      effect of hydrochlorothiazide on the plasma concentration and renal excretion of
      oxipurinol is small. When taking both drugs, there is no increased risk during
      long-term treatment, and a risk is even questionable during the first days.

PMID- 7711419
TI  - Interaction of allopurinol and hydrochlorothiazide during prolonged oral
      administration of both drugs in normal subjects. II. Kinetics of allopurinol,
      oxipurinol, and hydrochlorothiazide.
AB  - The kinetics of allopurinol and hydrochlorothiazide were investigated in seven
      healthy male subjects during prolonged coadministration of two drugs. Subjects
      were maintained on an isoenergetic, purine-free formula diet with RNA
      supplementation for 24 days. Allopurinol (300 mg) was given orally on days 1-24.
      Hydrochlorothiazide (50 mg daily) was added to days 11-21. On day 43 a single
      oral dose of 50 mg hydrochlorothiazide was administered. Plasma concentration
      time profiles of allopurinol and its main metabolite oxipurinol were obtained on
      days 1, 10, and 21; hydrochlorothiazide profiles were assessed on days 21 and 43.
      In addition, 24-h plasma concentrations of oxipurinol were measured repetitively,
      and 24 h urine samples were collected for the determination of allopurinol,
      oxipurinol, and hydrochlorothiazide. For oxipurinol, mean Cmax was not altered on
      hydrochlorothiazide treatment (13.8 +/- 1.4 micrograms/ml and 14.7 +/- 2.6
      micrograms/ml, respectively); mean AUC0-24 was 259 and 290 micrograms h-1 ml-1,
      respectively. The small difference in AUC0-24 values does not explain the
      increase in plasma uric acid concentration during hydrochlorothiazide treatment,
      nor do the variations in allopurinol and hydrochlorothiazide kinetics.

PMID- 7711420
TI  - Comparison of serum fluoride levels after administration of monofluorophosphate
      calcium carbonate or sodium fluoride: differences in peak serum concentrations.
AB  - Fluoride salts are widely used in Europe in the treatment of established
      osteoporosis with crush fractures for their ability to increase trabecular bone
      mass. However, in the United States fluorides are still regarded as an
      experimental drug. In a prospective, randomized study we compared the fluoride
      pharmacokinetics of enteric-coated sodium fluoride and disodium
      monofluorophosphate calcium carbonate (MFP-Ca) over the period of 76 h. Twenty
      subjects (12 females, 8 males), aged 35-80 years, free of gastrointestinal
      disorders, renal impairment, and liver disease and without prior fluoride intake
      entered the study. Ten subjects received NaF (11.3 mg fluoride) twice a day and
      the other ten MFP-Ca (13.2 mg fluoride) twice a day. During the study period of
      76 h the patient's usual food intake was not changed. Serum fluoride levels were
      determined using an ion sensitive electrode. After intake of a single drug
      preparation of MFP-Ca or NaF, MFP-Ca showed a significantly shorter lag time of
      absorption and a significantly higher maximal serum fluoride concentration than
      NaF (P < 0.01). A comparison of fluoride cumulative characteristics of both drugs
      showed virtually identical serum fluoride levels before intake of the morning
      dose on all 4 study days, whereas serum fluoride concentrations measured 4 h
      afterwards were significantly higher for MFP-Ca than for NaF. These data provide
      evidence of high "peak" serum fluoride levels for MFP-Ca, whereas only small peak
      to-trough fluctuations are seen for NaF.

PMID- 7711422
TI  - Habent sua fata libelli (books have their fate)

PMID- 7711421
TI  - Liposomal tretinoin for uncomplicated acne vulgaris.
AB  - Frequently occurring skin irritancy and flare-up reactions impede the use of
      topical tretinoin for acne vulgaris due to poor patient compliance. Liposome
      encapsulation improves penetration into the skin and local tolerability in
      animals. We investigated efficacy and local tolerability of liposomal tretinoin
      in man. In a double-blind study 20 patients with uncomplicated acne vulgaris
      received liposomal tretinoin (0.01%) on one side of the body and a commercial gel
      preparation with either 0.025% or 0.05% on the other once daily for 10 weeks.
      Comedones and papules/pustules were counted every 2 (-4) weeks. Then also
      redness, scaling, and burning were rated according to a four-point scale.
      Moreover, the patients noted skin irritancy in a diary on a daily base. With
      conventional tretinoin the gels were equally efficacious and equally well
      tolerated. Liposomal tretinoin also appeared equipotent to the reference gels.
      There may even have been a slightly more rapid clearing of comedones following
      the liposome preparation. With respect to skin irritancy, however, liposomal
      tretinoin was superior. As rated by the patients, liposome encapsulated tretinoin
      induced less burning (mean cumulative score 2.7 +/- 1.2) than the 0.025% gel
      (16.1 +/- 7.1) and the 0.05% gel (9.7 +/- 4.1) gel and less erythema (1.8 +/-
      0.7) than the 0.025% gel (11.4 +/- 3.8; (P < 0.05). Liposomal tretinoin was also
      better tolerated according to the rating by the investigator. Liposomal
      encapsulation of tretinoin allows reduction of the concentration of the active
      agent without a decline in efficacy for acne vulgaris. Since local tolerability
      is thus increased, liposomal tretinoin should favor the acceptance of this
      treatment by the patient.

PMID- 7711423
TI  - The prognostic value of hypocholesterolemia in hospitalized patients.
AB  - Clinical observations show that severe illness often leads to
      hypocholesterolemia. To verify this finding and to define the relationship
      between serum cholesterol and a patient's prognosis, a study was conducted in two
      large hospital populations. Of 24,000 and 61,463 adult patients (populations I
      and II) an average of 3.8% and 3.6% died in hospital, respectively. The mean
      serum cholesterol levels of patients who died was significantly lower than that
      of those who survived (163.6 mg/dl versus 217.8 mg/dl; P < 0.0001). The average
      cholesterol of surviving patients was similar to that of 6,543 healthy controls.
      During hospitalization serum cholesterol levels of < or = 100 mg/dl were
      encountered in 1.2% and 3.6% of patients of populations I and II, respectively.
      The mortality of these hypocholesterolemic patients was about tenfold higher than
      average and showed a strong, inverse, linear relationship with serum cholesterol
      concentrations. Patients whose serum cholesterol level dropped to less than 45
      mg/dl did not survive. These data show that in severely ill patients serum
      cholesterol may decline to very low concentrations, and the prognosis is
      reflected by the degree of hypocholesterolemia, which thus may serve as a
      clinically useful prognostic parameter.

PMID- 7711424
TI  - Plasma lipids and lipoproteins and essential hypertension.
AB  - In recent years there have been many studies demonstrating a correlation between
      increased arterial blood pressure and altered lipid profiles, and there has been
      an especially positive correlation between high cholesterol levels and blood
      pressure. There are differences between the various reports that are important.
      In our study the lipid distribution in 105 hypertensive patients with mild or
      moderate arterial hypertension according to WHO criteria without clinically or
      ultrasonographically apparent atherosclerosis was compared to the lipid
      distribution in 65 age-matched healthy persons. On the epidemiological level a
      significant, positive association was found between LDL serum levels (P < or =
      0.001), Apo B serum levels (P < or = 0.001), serum triglyceride levels (P < or =
      0.05) and VLDL serum levels (P < or = 0.01) and arterial hypertension. However,
      in contrast to recent reports, no significant difference was found between total
      serum cholesterol levels in normotensives and hypertensives, and there was no
      difference in HDL serum levels. No evidence could be found for a significant
      increase in lipoprotein (a) serum levels in hypertensives.

PMID- 7711425
TI  - Lecithin-cholesterol acryltransferase activity in patients with coronary artery
      disease examined by coronary angiography.
AB  - This study grew out of observations of certain lecithin:cholesterol
      acyltransferase (LCAT) abnormalities in patients with atherosclerosis. We studied
      the interrelationships among LCAT, and total cholesterol, free and esterified
      cholesterol, cholesterol in individual lipoprotein fractions, triglycerides,
      phospholipids, free fatty acids, L-lactates in 90 angiographically examined
      patients with coronary artery disease and 30 control subjects without clinical
      manifestations of coronary artery disease. Results of the study showed LCAT
      activity to be significantly decreased (P < 0.05) in patients with single-,
      double-, or triple-vessel disease than in disease-free subjects. LCAT was also
      found to follow the stage of coronary artery disease in angiographically examined
      patients. Decreased LCAT activity was accompanied by lower high-density
      lipoprotein cholesterol, elevated ratio of unesterified to esterified
      cholesterol, and increased levels of L-lactates, free fatty acids, and low
      density lipoprotein cholesterol. Total cholesterol and triglycerides were within
      or slightly above the normal limits. The results show LCAT to be a significantly
      better indicator of the risk of coronary artery disease than either total
      cholesterol or triglycerides.

PMID- 7711426
TI  - Limited trypsin proteolysis renders carnitine palmitoyltransferase insensitive to
      inhibition by malonyl-CoA in patients with muscle carnitine palmitoyltransferase
      deficiency.
AB  - Carnitine palmitoyltransferase (CPT) was studied in muscle homogenates of two
      patients with muscle CPT deficiency heterozygous for the Ser-113 Leu mutation in
      the CPT II gene. Total CPT activity was normal in both patients but was almost
      completely inhibited by malonyl-CoA and Triton X-100 whereas in controls 38% and
      58% of total activity remained in the presence of malonyl-CoA and Triton X-100,
      respectively. The addition of 1% Tween 20 abolished about half of the activity in
      patients but not in controls. Preincubation of muscle homogenate with trypsin
      slightly increased the total activity and rendered the activity greatly
      insensitive to inhibition by malonyl-CoA in both patients and controls. The data
      support the view that in patients with muscle CPT deficiency both CPT I and II
      are active, but that CPT II is abnormally accessible to inhibition by malonyl
      CoA.

PMID- 7711427
TI  - Effects of captopril treatment versus placebo on renal function in type 2
      diabetic patients with microalbuminuria: a long-term study.
AB  - We evaluated the renal effect of long-term antihypertensive treatment (12 months)
      with the angiotensin-converting enzyme inhibitor captopril compared to placebo in
      15 type 2 diabetic patients with microalbuminuria. The patients were randomly
      allocated to captopril (n = 9) or placebo (n = 6). After 1-year therapy no
      significant decrease in blood pressure was demonstrated with captopril (139 +/-
      17/80 +/- 9 versus 138 +/- 13/76 +/- 6 mmHg) or placebo (138 +/- 9/75 +/- 6
      versus 135 +/- 14/79 +/- 10 mmHg). Only in a small hypertensive subgroup (n = 4)
      treated with captopril did we find a significant reduction in blood pressure (154
      +/- 2/88 +/- 1 versus 142 +/- 7/78 +/- 5 mmHg, P < 0.05). The urinary albumin
      excretion rate did not change significantly either in the captopril group (95.6
      mg/24 h, 25th percentile 138.4, 75th percentile 25.1; versus 127.8 mg/24 h, 25th
      percentile 29.3, 75th percentile 222) or in the placebo group (99.2 mg/24 h, 25th
      percentile 58.5, 75th percentile 125.8; versus 120.9 mg/24 h, 25th percentile
      62.1, 75th percentile 179.7). There were also no alterations in renal blood flow
      or filtration rate. In the hypertensive subgroup treated with captopril a
      reduction in urinary albumin excretion rate after 3 and 6 months of treatment was
      observed (captopril 73.4 versus 24 and 41 mg/24 h, P < 0.05), but not after 12
      months. Triglyceride and cholesterol levels remained constant before and after
      treatment while glycosylated hemoglobin decreased significantly after 12 months
      captopril (7.8 +/- 0.9 versus 6.9 +/- 0.7 mg%, P < 0.03).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7711428
TI  - Effectiveness of prophylactic therapy on goiter recurrence in an area with low
      iodine intake--a sonographic follow-up study.
AB  - There is no agreement as to whether or not drug treatment after surgery for
      nodular goiter is effective in preventing recurrence of goiter. Data about
      recurrences in areas of marginally low iodine intake (like Germany) vary widely.
      Therefore, we performed a retrospective study in 104 patients who had been
      treated surgically because of benign uninodular or multinodular goiter. The mean
      follow-up period was 6.4 years (minimal 1 year) with at least three examinations.
      Thyroid ultrasound with volumetric analysis was recorded in each patient. Thirty
      two patients did not receive any prophylaxis, 50 patients were treated with L
      thyroxine, 17 patients with a combination of L-thyroxine and iodine and 5
      patients with iodine alone. Recurrence of goiter was documented in 28.0% of the
      untreated patients and in 8.9% of the patients on prophylaxis (P < 0.05). The
      mean increase of thyroid volume was 7.3 ml versus 3.1 ml in patients without
      versus with prophylactic drug treatment (not significant). No significant
      correlation was found between the increase of thyroid volume and age of the
      patients, follow-up time, or initial thyroid volume, respectively. These data
      clearly demonstrate the effectiveness of prophylactic drug therapy to prevent
      recurrence of goiter after thyroid surgery in an iodine-deficient area.

PMID- 7711429
TI  - Comparison between ethanol sclerotherapy and emptying with injection of saline in
      treatment of thyroid cysts.
AB  - We compared the results of ethanol sclerotherapy in thyroid cysts with emptying
      of cysts and instillation of saline. Twenty-six patients with recurrent thyroid
      cysts were treated with cyst aspiration and subsequent ethanol sclerotherapy. A
      control group of 44 patients was submitted to cyst aspiration and subsequent
      injection with isotonic saline; among them 20 had previously been treated with
      repeated aspirations of the cyst fluid. The patients were followed up clinically
      and ultrasonically 1 and 12 months after treatment. Cure was defined as the
      absence of any residual cystic lesion or an ultrasonic cyst volume less than 50%
      of basal after 12 months from the start of treatment. Cytological study showed
      all of the lesions to be benign. Of the 44 patients in the saline group 16 (36%)
      were cured, among whom 6 of 20 had previously been submitted to repeated
      aspirations. Among the 26 patients treated with ethanol sclerotherapy 20 (77%)
      were cured. Statistical analysis revealed a significantly higher effectiveness of
      treatment with ethanol than that with emptying and saline instillation (chi
      square, P = 0.002) or with repeated aspiration and saline instillation (chi
      square, P = 0.003). Slight pain was observed in two patients treated with saline
      and five treated with ethanol sclerotherapy. Three patients treated with ethanol
      sclerotherapy presented severe pain and one transitory hyperthyroidism. We
      conclude that ethanol sclerotherapy is effective and safe in the treatment of
      thyroid cysts.

PMID- 7711430
TI  - Suppressed thyroid-stimulating hormone secretion in patients treated with
      interleukin-2 and interferon-alpha 2b for metastatic melanoma.
AB  - Recent reports suggest that combined therapy with recombinant interleukin (IL)-2
      and interferon (IFN) alpha 2b may result in autoimmune-induced thyroid
      dysfunction. We prospectively analyzed thyroid function for 6 weeks in two groups
      of patients with progressive metastatic melanoma treated according to two
      different protocols. In group I (n = 17) three treatment cycles were given, each
      with three weeks of subcutanous administration of rIL-2 and INF-alpha 2b at
      different doses. In group II (n = 13) the chemotherapeutic agent dacarbazine was
      given in addition. In group 1 three patients developed frank hyperthyroidism,
      which required antithyroid drug therapy in one case. Autoantibodies against
      thyroid microsomal antigen, thyroglobulin, and the thyroid-stimulating hormone
      (TSH) receptor were not significantly elevated in any of these patients. However,
      the remaining 14 patients showed a significant decrease in TSH after 6 weeks of
      treatment, from 1.8 +/- 0.9 to 0.7 +/- 0.7 microU/ml (P < 0.02). Thyroid hormones
      (triiodothyronine, thyroxine, free thyroxine) also increased during the
      observation time, but this did not parallel the drop in TSH levels. Only
      thyroxine increased above the upper limit of normal, while triiodothyronine and
      free thyroxine stayed within the normal range. In group II, 6 of 13 patients
      (46%) had a decreased TSH after 6 weeks of treatment. Mean TSH was 1.5 +/- 1.4
      before and 0.8 +/- 0.6 microU/ml after 6 weeks and was totally suppressed in
      three cases. None of these patients showed ouvert hyperthyroidism. Hypothyroidism
      was not observed in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711431
TI  - Primary aldosteronism: difference in clinical presentation and long-term follow
      up between adenoma and bilateral hyperplasia of the adrenal glands.
AB  - Since 1974 primary aldosteronism has been diagnosed in 71 patients in our
      outpatient clinic. Thirty-four patients had a unilateral aldosterone-producing
      adenoma, whereas bilateral adrenal hyperplasia was diagnosed in 37 patients.
      Although at the time of diagnosis the mean potassium values were lower and mean
      aldosterone levels were higher in patients with an adenoma, as compared to those
      with bilateral hyperplasia, these laboratory data did not allow us to
      differentiate between the two leading causes of primary aldosteronism in the
      individual patient due to pronounced overlap of laboratory values between the two
      groups. During the first few years, a successful differential diagnosis was made
      by adrenal phlebography and separate sampling of plasma aldosterone in both
      adrenal veins; later non-invasive imaging techniques such as computed tomography
      and radionuclide scanning were used. The best results were obtained in patients
      with adenoma who underwent adrenalectomy. Fifty-six percent of these patients
      were clinically and biochemically cured; 28% were improved and had normal blood
      pressure values during drug treatment. In contrast, patients with bilateral
      hyperplasia were treated pharmacologically, but only in half of the patients
      could normal blood pressure values be achieved. Two thirds of the male patients
      developed gynecomastia during spironolactone treatment. As expected, unilateral
      adrenalectomy was unsuccessful in the 7 patients with bilateral hyperplasia who
      underwent surgery. Our results confirm that surgical treatment of adrenal
      adenomas and drug treatment of bilateral hyperplasias are the appropriate therapy
      in primary aldosteronism. A differential diagnosis cannot be made on the basis of
      clinical and non-invasive laboratory data alone; imaging techniques have to be
      included in the diagnostic process.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711432
TI  - Volumes and Na+/H+ antiporter activity of lymphocytes in patients with congestive
      heart failure.
AB  - Previous studies in patients with congestive heart failure (CHF) treated with
      diuretics and/or digoxin have shown abnormalities of cellular volume and
      electrolytes in biopsies of skeletal muscle. These abnormalities seem to play an
      important role with regard to the dysregulation of peripheral vascular resistance
      and characteristic clinical features of CHF, for example, muscular weakness. This
      study assessed the effect of angiotension-converting enzyme (ACE) inhibitor
      therapy on cell volume and cell volume regulation in patients with CHF. Cell
      diameters of human mononuclear leukocytes (HML) were determined electronically by
      a Coulter Counter. Cell diameters for 19 patients with decreased left ventricular
      ejection fraction (determined via levocardiography) on therapy with ACE
      inhibitors (group 1) were compared to those of HML from patients on diuretics
      alone (group 2, n = 16). The activity of the Na+/H+ antiporter was determined by
      cell swelling in isotonic propionate. The control group consisted of 20 normal,
      age- and sex-matched volunteers. HML diameters were significantly increased from
      7.16 +/- 0.07 in normals to 7.24 +/- 0.08 microns (group 1; P < 0.01) and 7.23 +/
      0.11 microns (group 2; P < 0.05), indicating an abnormal regulation of cell
      volume. There were no statistically significant correlations between the
      individual ejection fraction or digoxin therapy and average cell diameters. In
      both patient groups ethylisopropylamiloride-sensitive swelling rates were normal
      compared to the control group indicating a normal activity of the Na+/H+
      antiporter. In conclusion, increased cell sizes reflect a structural change in
      HML rather than a rapidly reversible functional abnormality which was not
      affected different by ACE inhibition and diuretic therapy.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7711434
TI  - Are heart rate responses reproducible in the tilt-table test?
AB  - Measurement of blood pressure and heart rate in active orthostasis has proven to
      be effective in the diagnosis of autonomic regulatory dysfunctions. The following
      study was carried out in order to clarify to what extent reproducible heart rate
      reactions also occur in passive orthostasis. 61 people with normal results in
      five standardized tests were examined. All 61 test persons had individually
      differing courses of heart rate. After an initial increase of frequency an almost
      straight line results from a superimposed projection of the graphs. In 20 of
      these cases the tilt-table test was repeated in order to detect intra-individual
      regularities. Even when the test was repeated, no reproducible intraindividual
      heart rate reactions occurred. And here as well, projection of the graphs
      produced an almost straight line. We could not find any quotient, such as the
      30/15 ratio in active orthostasis, during our tests with the tilt-table.

PMID- 7711433
TI  - Cyclosporine A enhances total cell calcium independent of Na-K-ATPase in vascular
      smooth muscle cells.
AB  - The effect of cyclosporine A in enhancing vasconstrictor-induced calcium (Ca2+)
      mobilization in vascular smooth muscle cells may contribute to important side
      effects in cyclosporine therapy such as hypertension and nephrotoxicity. As we
      have previously shown, cyclosporine A stimulates transmembrane Ca2+ influx. Since
      Ca2+ efflux was not affected by cyclosporine A, we concluded that cyclosporine
      augments angiotensin II induced Ca2+ mobilization in vascular smooth muscle cells
      by an increased amount of Ca2+ in angiotensin II sensitive intracellular Ca2+
      stores. The present study was therefore designed to examine the effect of
      cyclosporine A on cellular calcium content and on membrane calcium transport
      mechanisms. An important mechanism of Ca2+ extrusion from the cell is the Na-Ca
      exchanger. Its activity is closely related with that of the Na-K-ATPase. By
      increasing cellular sodium concentration the blockade of Na-K-ATPase would in
      turn activate cellular calcium uptake bx the Na-Ca exchanger. Therefore, we
      hypothesized that cyclosporine A might exert its effects in the same manner as a
      circulating Na-K-ATPase inhibitor. Total cell calcium was measured by atomic
      absorption and activity of Na-K-ATPase was estimated by an assay measuring
      phosphate production. Preincubation of the cells with cyclosporine (10
      micrograms/ml) for 15 min increased total cell calcium from 31.4 +/- 5.0 to 46.5
      +/- 5.3 nmol/mg protein (P < 0.05). Activity of Na-K-ATPase was not affected by
      cyclosporine A (3.9 +/- 0.2 vs. 4.3 +/- 0.2 mumol Pi h-1 mg-1 protein).
      Therefore, cyclosporine A induced Ca2+ influx is not mediated by an inhibition of
      the Na-K-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711436
TI  - Intensive care and DRGs--where are we up to?

PMID- 7711435
TI  - Pain in the client experiencing myocardial ischaemia--nursing assessment and
      management. Part 1--neurophysiology and clinical manifestations of myocardial
      ischaemia pain.
AB  - Effective nursing management of the client experiencing myocardial ischaemia
      requires the nurse to integrate skills of clinical assessment (incorporating
      physiological and psychological domains), knowledge of myocardial oxygen supply
      and demand, knowledge of pain pathways and autonomic nervous system responses and
      appropriate nursing and pharmacological therapeutics. Part 1 of this article aims
      to describe cardiac pain pathways and the subsequent autonomic nervous system
      responses. This is necessary for the nurse to fully understand the clinical signs
      and symptoms found on clinical assessment of a client experiencing myocardial
      ischaemia. This myocardial ischaemia may manifest as pain. The concept of silent
      ischaemia will also be discussed as the critical care nurse must also be skilled
      in assessing a client experiencing myocardial ischaemia in the absence of pain.
      Part 2 in the next issue will provide a systematic framework for the nursing
      assessment of the client and discuss appropriate nursing and pharmacological
      therapeutics to reduce myocardial ischaemia.

PMID- 7711437
TI  - Specialist nurse education in Australia.

PMID- 7711438
TI  - The usefulness of intensive care treatment: perspectives of medical and nursing
      staff.
AB  - Which patients' states or circumstances effect the judgement of Intensive Care
      specialist (IC) medical and nursing staff as to how useful intensive care
      treatment is? Do IC medical and nursing staff differ significantly in their
      attitudes regarding the usefulness of IC treatment? Or do they show similarity in
      their attitude but differ as a group from broader community views of the
      usefulness of IC treatment? To gain insight into these questions a group of IC
      staff (35 medical, 108 nursing) and pre-clinical students (110 medical, 136
      nursing) responded to a questionnaire asking them to consider how 12 patient
      factors including age, functional state, socioeconomic factors, length and cost
      of the IC stay, culpability, disease state and length of survival after IC unit
      discharge effected their judgement of the usefulness of IC treatment for an
      individual patient. Results indicated that: (i) medical and nursing students felt
      IC treatment more useful than IC staff regardless of the patient characteristic;
      (ii) IC doctor and nurse responses were very similar; (iii) IC staff considered
      that IC treatment "tended to be useless" or was "useless" if the patient had
      required "institutional care", was in a "vegetative" state before or after IC
      treatment, belonged to the pathology groups of "malignancy" and "diseases of
      ageing", belonged to the diagnostic groups "AIDS" and "quadriplegia", or where
      survival post discharge from IC was expected to be "< 3 months"; and (iv) cost
      and length of stay in IC were not factors that negatively effected any groups
      perception of the usefulness of IC treatment.

PMID- 7711439
TI  - 'Critical care and our ageing society'.

PMID- 7711440
TI  - The criteria used for reviewing abstracts.

PMID- 7711441
TI  - Receptors, photoreception and brain perception. New insights.
AB  - Once photons have activated photosensitive cell receptors, a biochemical process
      mediated by G-proteins transforms the initial signal into nerve potentials. The
      generated impulses transmit the information through ganglion cells, after a
      complex interaction with other neurons by means of different neurotransmitters.
      Since visual function is processed in parallel, ganglion cells are divided into M
      neurons which are in charge of capturing large objects, P-neurons capable of
      analyzing fine details and colors, and non-M, non-P neurons which are sensitive
      to changes in light intensity. Retina, bipolar and ganglion cells share circular
      receptive fields with an antagonistic surround whereas the lateral geniculate
      nucleus possesses rectangular receptive fields. Thus, when central cones are
      stimulated, ON-center cells depolarize, while OFF-center cells hyperpolarize. At
      the brain cortex, the magnocellular layers lead to orientation and achromatic
      perception, the parvocellular layers perform color vision in the blobs and
      achromatic contrast and orientation in the interblobs, and eventually, binocular
      perception is the result of multiple disparities phenomenon. On these bases,
      patients with agnosia for form and pattern or for depth and movement have been
      described. Likewise, color blindness is another disease that could be the result
      of photoreceptor dysfunctions or brain perception defects.

PMID- 7711442
TI  - An assessment of cerebrospinal fluid's total creatine-kinase activity in the
      differential diagnosis of metabolic and organic causes of coma.
AB  - The objective of the study was to assess total cerebrospinal creatinine-kinase
      activity (CSF-CK) measurement in differential diagnosis of "metabolic" and
      organic causes of coma. The setting for the study was a tertiary care reference
      medical center and community general hospital. The design of the study was a
      series of consecutive patients with profound coma (Glasgow scale ratings between
      3 and 6) as the presenting complaint to the emergency room and controls.
      Measurements and main results were as follows: CSF-CK was measured in 103
      consecutive patients including 18 patients with metabolic causes of coma, 27
      patients with organic causes of coma, 18 patients scheduled for elective
      orthopedic surgery with epidural anesthesia and 27 patients with compressive
      myelopathy and radiculopathy. CSF-CK activities were significantly different
      between groups (H = 29.48, p < 0.001, Kruskal-Wallis test), controls had a median
      of 0 mU/ml (range 0-16 mU/ml), patients with metabolic causes of coma had a
      median of 0 mU/ml (range 0-65 mU/ml), patients with compressive myelopathy or
      radiculopathy had a median of 19 mU/ml (range 0-80 mU/ml), and patients with
      organic causes of coma had a median of 20 mU/ml (range 0-400 mU/ml). The test
      sensitivity was 83% (95% confidence interval (CI 65-100%) specificity 62% (CI 43
      80%) positive predictive value 60% (CI 49-79%) and negative predictive value 85%
      (CI 75-95%). The conclusion of the study was that the test is useful for ruling
      out metabolic causes of coma when CSF-CK activity is high (i.e., above 16 mU/ml).

PMID- 7711443
TI  - Inappropriate treatment in children with bloody diarrhea: clinical and
      microbiological studies.
AB  - It is suggested that in dysentery physicians should treat empirically, as early
      treatment seems to improve outcome. A constantly updated knowledge of the
      relative frequency of enteropathogens and their sensitivity to antimicrobials is
      needed to choose the right therapy. We studied microbiological and clinical
      findings in 119 children with bloody diarrhea in Mexico City. Patients were
      divided into those < 1 year (infants) and those 1-5 years (children). Shigella
      was more frequent in children (35%) than in infants (10%). Campylobacter was more
      common in infants (29%) than in children (12%); Salmonella more frequent in
      infants (22%) than in children (8%); cytotoxic E. coli (EHEC) more frequent in
      children (20%) than in infants (13%). No cases of amebiasis were identified.
      Fever was the most sensitive indicator of infection for Shigella (70%), as
      compared for Salmonella (50%), Campylobacter (42%) and EHEC (36%); whereas
      specificity was about 50% for all pathogens. In contrast, the absence of fever
      was 80% predictive for the absence of these pathogens. In children with
      dysentery, the specific etiology cannot be predicted in the absence of culture.
      Almost 50% of the Shigella, Salmonella and EHEC isolates were resistant to
      ampicillin. In our community, the use of ampicillin and metronidazole should be
      discouraged.

PMID- 7711444
TI  - Malnutrition as an adverse prognostic factor in patients with diffuse large cell
      lymphoma.
AB  - To assess the usefulness of nutritional status at diagnosis, we studied a group
      of 87 adult patients with diffuse large cell lymphoma (DLCL) in a prospective
      clinical trial. Nutritional status (NS) was measured by the combination of
      triceps skinfold, arm circumference and serum determinations of albumin and
      transferrin. Normal values were considered if the nutritional index was < 40,
      malnutrition was considered when the nutritional index was > 40. Fifty one (58%)
      of the patients presented with malnutrition at diagnosis with a nutritional index
      > 40. Malnourished patients had a significantly poorer outcome than well
      nourished patients because overall survival was better: 57+ months (mean) in well
      nourished patients compared to only 14 months (mean) in malnourished patients.
      Disease-free survival was also better in the patients with normal NS: 48%
      compared to 10% in patients with abnormal NS. Chemotherapy was better tolerated
      in the well-nourished cases with less delay in treatment schedule, less episodes
      of severe myelosuppression and infection and more dose intensity than patients
      with nutritional index > 40. Multivariable analysis indicates that malnutrition
      was a poor prognostic factor independent of other prognostic factors. We believe
      that malnutrition itself might be included as an adverse prognostic factor in
      patients with DLCL and studies to improve this clinical situation will be
      conducted.

PMID- 7711445
TI  - Effect of plasma volume expansion on auricular natriuretic peptide in non
      dependent insulin diabetic patients with autonomic neuropathy.
AB  - The objective of this study was to determine the role of atrial natriuretic
      peptide (ANP) in autonomic neuropathy and to learn the effect of saline solution
      infusion on ANP. Twenty one subjects were distributed in three groups: 1) control
      group, 2) diabetic patients with autonomic neuropathy, and 3) diabetic patients
      without autonomic neuropathy. The levels of ANP, renin, aldosterone and cortisol
      were determined at baseline and 30, 60, and 75 min after saline infusion. At
      baseline ANP was lower in diabetic patients with autonomic neuropathy (32.9 +/-
      13) than control group (34 +/- 15). ANP increased statistically significantly at
      30 min after solution administration in control group (60 +/- 35, F = 4, p <
      0.05), but it did not change in diabetic patients (Group II: 34.3 +/- 9.3 and
      Group III 34.6 +/- 10.7). Sixty and 75 min after saline infusion ANP returned to
      basal levels in control group, but they did not change in diabetic patients. A
      delayed response of renin, aldosterone and cortisol to saline solution
      administration was observed in diabetic patients. There was no correlation
      between ANP levels and alteration of autonomic tests. It is concluded that
      independent of autonomic neuropathy, the levels of ANP did not increase with
      saline infusion in diabetic patients.

PMID- 7711446
TI  - Participation of the kidney in the kinetics of arginine vasopressin in the water
      loaded rat.
AB  - The kidney is a target organ for antidiuretic hormone (ADH) and it is also the
      main organ involved in the clearance of this hormone. There is controversy on the
      mechanisms involved in the renal handling of ADH, mainly in regard to whether it
      is secreted or reabsorbed. Kinetic and renal clearance studies of ADH were
      performed in water-loaded rats and were compared with inulin (glomerular
      filtration marker) and tetraethylammonium (TEA, marker of organic cation
      secretion). The kinetics of the three molecules fitted a bicompartmental model.
      Distribution constants of [125I]-ADH were twofold higher than those of inulin.
      Elimination constant was higher for inulin than for ADH (0.049 +/- 0.001 vs.
      0.020 +/- 0.003 min-1, respectively), suggesting reabsorption of the hormone. The
      ratios of Clearance ADH/Clearanceinulin and ClearanceTEA/Clearanceinulin were
      0.14 and 4.86, respectively. In summary, data from kinetic studies and from renal
      clearances suggested that ADH is reabsorbed.

PMID- 7711447
TI  - Taurine content in breast milk of Mexican women from urban and rural areas.
AB  - The concentration of the most abundant free amino acids in breast milk, taurine,
      glutamic acid, glycine + threonine, alanine and glycine was measured in breast
      milk samples obtained from Mexican women from an urban population (38 samples)
      and from a rural population (106 samples). Free amino acid levels including
      taurine in the urban group were essentially similar to those reported in samples
      from American and Canadian women (taurine concentration: 332-357 nmol/ml) but
      significantly lower content of taurine (237-259 nmol/ml) was found in the rural
      group. The only other significant difference between the two groups was a 32%
      higher concentration of alanine in the rural group as compared to the urban
      group. The observed differences may result from a lower dietary intake of taurine
      containing food in the rural group as this group reported a restricted
      consumption of meat, the most abundant dietary source of taurine. Because taurine
      synthesis is low in primates including human, a decreased external supply of
      taurine may explain the observed reduction in the taurine content of milk. The
      increase in alanine may represent a compensatory mechanism for the decrease in
      taurine.

PMID- 7711448
TI  - Molecular analysis of the phenylalanine hydroxylase gene in Mexican
      phenylketonuric patients.
AB  - The molecular analysis of the human phenylalanine hydroxylase (PAH) gene in
      Mexican phenylketonuric (PKU) patients is described. We analyzed the restriction
      fragment length polymorphism (RFLP) haplotypes of five probands and ten non
      affected relatives, belonging to four unrelated PKU families. Twenty-nine alleles
      were typified, corresponding to 12 different haplotypes. Eight RFLP haplotypes
      corresponded to those described in other populations, while the remaining were
      unreported haplotypes, appearing both on normal and PKU chromosomes. Using the
      polymerase chain reaction (PCR) and the allele-specific oligonucleotide assay
      (ASO), we also screened for the IVS10 mutation, one of the most common PAH gene
      mutations in Mediterranean countries. Forty-two percent of the PKU chromosomes
      analyzed bore the IVS10 mutation, although it was present in the heterozygous
      state in all cases. Our data show an important genetic heterogeneity at the PAH
      locus in the Mexican population, and report the genetic influence of the Spanish
      immigration to the American continent.

PMID- 7711449
TI  - Rabies veterinary virus vaccine produced in BHK-21 cells grown on microcarriers
      in a bioreactor.
AB  - BHK-21 cells were grown in microcarriers in the CELLIGEN CL 50 bioreactor to
      produce a stock of rabies veterinary virus vaccine PV (Pasteur virus) strain.
      Perfusion mode operation of this bioreactor produced between two- and fourfold
      larger yields (cells/ml) than traditional stationary cell culture systems (i.e.,
      Blake, and Roller bottles or cell factory multitrays). The method employed
      harvested 281 of rabies virus in 200 h (infectivity titer 0.6 +/- 1.4 x 10(7)
      LD50 per ml) in a single operation. The risk of contamination is thus reduced
      when compared with traditional stationary methods which, in order to obtain the
      same amount of virus, would require the operation of 285 Blake bottles, or 143
      Roller bottles, or 15 Cell Factory multitrays (10 trays). By perfusion mode
      operation of the bioreactor, 89% of the cell culture medium was recovered as
      vaccinal virus, which contrasts with the yield of only 50-59% using traditional
      cell culture systems. On the other hand, only 925 ml of fetal serum was required
      to obtain the 281 of rabies virus harvest as compared to the 3420 ml required by
      traditional methods.

PMID- 7711450
TI  - Red blood cell indices in a high altitude hospital population.
AB  - It is currently accepted that the red blood cell indices (MCV, MCH and MCHC) are
      the same in general care hospital populations throughout the world. The aim of
      the study was to explore whether the internationally accepted values for red cell
      indices are the same in a hospital located in Mexico City at 2240 meters above
      sea level (7352 feet). The setting for the study was a third level specialized
      care hospital for adults with chronic degenerative problems (trauma and obstetric
      cases were not seen). Each day, for a period of 139 working days, 120 EDTA blood
      samples of patients were assayed within 3h of extraction in a flow cytometer
      analyzer (Coulter STKR). Using the moving average approach of Bull (Reference 3)
      in batches of 20 samples, a raw daily value for each indice was obtained with the
      mean of the six daily moving averages. The daily raw value was multiplied by a
      ratio (assigned/observed ratio) of the corresponding daily value obtained in a
      normal preserved blood control (Coulter's 4C): we refer to them as corrected
      values in this paper. A total of seven batches of the Coulter control were used
      to obtain the corrected values during the 139 days of observation. The results
      were as follows. The mean (SD) of correction values in the 139 days were: MCV =
      90.33 (.810) fl, MCH = 30.75 (.582) pg, MCHC = 33.38 (.630) g/dl. The indices
      showed significant changes in mean as a function of batch of the Coulter control
      used (F tests, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711451
TI  - Evaluation of the teratological potential of the new antihypertensive 5
      methoxytryptamine, beta-methylcarboxylate hydrochloride (indorenate) in mice.
AB  - 5-Methoxytryptamine, beta-methylcarboxylate hydrochloride (indorenate), a new
      antihypertensive agent, was examined for teratogenic-embryotoxic effects in the
      mouse at doses of 0 (control), 10, 20, 40, and 80 mg/kg/day. The compound was
      administered by gastric intubation on days 6-15 of gestation. On day 17, the dams
      were sacrificed, the number of live, dead, and resorbed fetuses recorded and mean
      pup weight determined. Teratological evaluation was carried out by visual
      inspection, alizarin red staining of the skeleton and Wilson's sections. Signs of
      overtoxicity in mothers were found in the high-dose groups. There were no
      differences between control and indorenate-treated groups in the number of
      implantations, live fetuses or anomalies. However, an embryotoxic effect was
      observed at 40 and 80 mg/kg, shown by increased resorptions and lower weight of
      pups at the higher dose.

PMID- 7711452
TI  - Total intravenous anesthesia with propofol vs. propofol/midazolam in oncology
      patients.
AB  - The goal of this study was to determine dose requirements of propofol vs.
      propofol/midazolam in oncology patients during total intravenous anesthesia. The
      design of the study was a controlled clinical trial. The setting was the Oncology
      Hospital, National Medical Center, IMSS, located in Mexico City. Sixty patients
      were allocated randomly into two groups, patients in control group received
      propofol and fentanyl to induced and to maintain the anesthesia. Twenty nine
      patients in the experimental group received propofol and midazolam to induce
      anesthesia and to maintain propofol and fentanyl. The combination of propofol and
      midazolam to induce general anesthesia in oncology patients reduced the
      requirements in propofol and fentanyl in total intravenous anesthesia.

PMID- 7711453
TI  - Changes in collagen content in the residual myocardium surviving after infarction
      in rats. Influence of propranolol or hydralazine therapy.
AB  - The changes occurring in the collagen content in the residual myocardium after
      infarction have been poorly studied. The aim of this study was to determine the
      changes in the collagen content in the right and left ventricular muscle of
      chronically infarcted hearts. Male albino rats were submitted to ligature of the
      left coronary artery to produce infarction (Inf). Controls underwent a sham
      surgery (Sh). Inf rats were divided into groups designed to receive chronic
      therapy with propranolol (Prop, 1 g/l, n = 10) or hydralazine (Hydr, 0.125 g/l, n
      = 10) dissolved in the drinking water. One group of Inf rats (n = 12) and the Sh
      group (n = 10) received no treatment. The animals were killed 1 month after
      surgery to obtain the cardiac wet weights and to determine protein and
      hydroxyproline (OH-Pro) concentrations in the right ventricle (RV) free wall and
      in the left ventricular remaining muscle (LV), including the interventricular
      septum. Inf determined a 42% increase of the RV weight to body weight ratio (Sh =
      0.57 +/- 0.04 mg/g; Inf = 0.81 +/- 0.06 mg/g; p < 0.05) and a 64% increase of OH
      Pro concentration (Sh = 450 +/- 25 micrograms/g; Inf = 738 +/- 32 micrograms/g; p
      < 0.05). In Inf hearts the LV OH-Pro concentration increased similarly as in the
      RV. No effect of drug therapy was observed in the LV. In the RV however,
      propranolol reduced the hypertrophy and the OH-Pro concentration by the same
      amount (around 30%). Hydr on the other hand reduced OH-Pro and tended to increase
      hypertrophy. We conclude that a similar collagen deposition occurs in the
      myocardium of both ventricles after infarction in rats. Prop and Hydr were able
      to partially reduce this collagen increase in the right but not in the left
      ventricle.

PMID- 7711454
TI  - Survival of cultured plant cells grafted into the subcutaneous tissue of rats
      (preliminary report).
AB  - To evaluate the survival of plant tissue in an animal environment, cultured calli
      from a Mexican medicinal plant (Mimosa tenuiflora Poir.) were transplanted under
      sterile conditions into the subcutaneous tissue of rats. Microscopic studies of
      grafted areas were carried out at the 30th, 60th and 120th days after
      transplantation. Histological evidence of plant graft survival was found in
      specimens of all groups. during the first month of subcutaneous grafting a
      moderate inflammatory reaction around the callus was observed characterized by
      the presence of polymorphonuclear cells and some macrophages and the formation of
      a fibrous capsule. Nevertheless, the plant grafts remained viable and a decrease
      of the inflammatory reaction around the callus was observed in the specimens
      during the following months. In the fourth month specimens the formation of blood
      vessels inside the grafted plant tissue was observed. Once removed from rats,
      plant tissues showed high viability according to the fluorescein test. These
      calli were then transferred to the original in vitro medium showing growth
      capacity during the following weeks. These results demonstrate, for the first
      time, that cultivated cells of higher plants survive in an animal environment,
      suggesting the possibility to utilize pharmacologically active plant transplants
      in animals, a technique proposed here as inter-regni transplants. Further studies
      are required to explore this new field of research that opens numerous questions
      about plant-animal cellular interaction.

PMID- 7711455
TI  - Effect of three immunostimulants on the resistance against Trichinella spiralis
      infection in mice. (preliminary report).
AB  - Twenty eight NIH mice were divided into four groups of seven animals each. Mice
      in groups were injected intraperitoneally with Freund's complete adjuvant (FCA),
      Concanavalin A (Con A), Equimune (EI) and phosphate buffered saline (PBS),
      respectively, 7 days before infection with 300 Trichinella spiralis infective
      larvae per animal. Forty two days after infection all mice were sacrificed and
      processed by artificial digestion to determine the number of larvae per gram
      (LPG) of muscle tissue. The mean +/- SD of LPG obtained were 59.8 +/- 13.1, 17 +/
      8.5, 3.3 +/- 6.2 and 71 +/- 11.5 for groups FCA, Con A, EI, and PBS,
      respectively. Significant reductions in larvae worm numbers, compared with non
      treated controls, were 76% and 95.3% in groups Con A and EI, respectively.

PMID- 7711456
TI  - Omphalocele-exstrophy-imperforate-anus-spina bifida (OEIS) complex in a male
      prenatally exposed to diazepam.
AB  - A male clinically affected by the OEIS complex was studied. His mother, aged 30
      years, has an affective disorder and ingested 30 mg of Diazepam daily, from 3
      months previous to the gestation and during the entire pregnancy. At birth, a
      closure during the entire pregnancy. At birth, a closure defect of the anterior
      abdominal wall, exstrophy of hemibladders, exposure of intestinal epithelium,
      abnormal pelvis, imperforate anus, and bifid penis were noted. Birth weight was
      3600 g and other measurements were not recorded. Colostomy was performed in the
      postnatal period followed by partial closure of the abdominal wall defect, and
      iliac osteotomies. At six years, 6 months of age, physical examination showed
      somatometric measurements around the third percentile (height 109 cm, weight 17
      kg, cephalic circumference 48.5 cm). Clinically he presented mild mental
      retardation, functional colostomy, incomplete closure of the vesical exstrophy,
      imperforate anus, bifid penis and scrotum, descended testes, diastasis of pubis,
      lumbosacral scoliosis and shortening of the left leg (clinical photograph of the
      external features is not included as we were not able to obtain authorization to
      do so). Radiological studies (Figure 1) revealed wide separation of the
      ischiopubic bones; lumbosacral region with rotoscoliosis, platyspondyly and
      dysraphism; left coxa valga, and right coxa vara. The abdominal ultrasonographic
      studies showed unilateral renal agenesis (left). Chromosomal analysis (GTG bands)
      in peripheral blood lymphocyte cultures demonstrated a normal 46,XY constitution.
      Exposure to other substances, particularly alcohol, were excluded with the study
      of the mother's medical history and through information obtained from
      relatives.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711457
TI  - Fielding H. Garrison Lecture. "A worrying profession": the domestic environment
      of medical practice in mid-nineteenth-century America.

PMID- 7711458
TI  - Major Greenwood versus Almroth Wright: contrasting visions of "scientific"
      medicine in Edwardian Britain.

PMID- 7711459
TI  - Scientific specialization and the poliovirus controversy in the years before
      World War II.

PMID- 7711460
TI  - The want of control: ideas, innovations, and ideals in the modern management of
      diabetes mellitus.

PMID- 7711461
TI  - Honor codes and medical ethics in modern France.

PMID- 7711462
TI  - [27th Congress of the German Association for Transfusion Medicine and
      Immunohematology. Saarbrucken, 19-22 October 1994. Abstracts].

PMID- 7711463
TI  - Oral L-arginine supplementation has no effect on cardiovascular responses to
      lower body negative pressure in man.
AB  - L-arginine is the physiological precursor of nitric oxide, which is the major
      endothelium-derived relaxing factor, a potent vasodilator. This study examined
      the cardiovascular responses to application of incremental levels (-10, -20 and 
      40 mmHg) of lower body negative pressure (LBNP) in ten normal male subjects,
      after 1 and 7 days administration of placebo or L-arginine. It was hypothesized
      that L-arginine may attenuate the vasoconstrictor response elicited by
      application of LBNP. Placebo administration had no effect on any responses to
      LBNP. L-arginine administration had no significant effect on mean arterial blood
      pressure either after 1 day, or after 7 days. After both 1 and 7 days L-arginine
      ingestion, forearm blood flow (FBF) and forearm vascular conductance (FVC) were
      significantly lower than before L-arginine ingestion (p < 0.01), but were not
      significantly different from after placebo ingestion. The magnitude of the
      changes in FBF and FVC, induced by application of LBNP, were not different under
      any conditions. These findings suggest that L-arginine supplementation in healthy
      subjects, either acutely or chronically, has no significant effect on peripheral
      haemodynamics, or on reflex responses to LBNP.

PMID- 7711464
TI  - Muscle spasm induced sympathetic reflex bursts on microneurography in a case with
      pontine demyelination.
AB  - Microneurography was performed in a 39-year-old woman with demyelination of the
      pontine white matter associated with muscle spasms in the lower extremities.
      Single bursts on the microneurogram were observed immediately after cessation of
      the spasm with no systemic changes in the blood pressure or heart rate. Voluntary
      tonic flexion of the lower extremities induced similar bursts with small
      amplitudes. These reflex bursts possessed a characteristic of muscle sympathetic
      nerve activity, because the latency between the peak of each burst and the prior
      R-wave on the electrocardiograph was constant. The occurrence of these bursts
      suggests that a segmental compensatory mechanism in the spinal cord may stabilize
      the muscle blood flow influenced by muscle contraction.

PMID- 7711465
TI  - Naloxone does not prevent apomorphine-induced emesis or hypotension in dogs.
AB  - Previous data have shown that apomorphine-induced respiratory depression can be
      reversed by the opiate antagonist, naloxone. The present study investigates the
      influence of naloxone on cardiovascular changes and vomiting elicited by
      apomorphine in dogs. In chloralose-anaesthetized animals, naloxone (0.02 mg/kg
      i.v.) failed to modify either the decrease in blood pressure and the biphasic
      changes (bradycardia followed by a long-lasting tachycardia in heart rate or the
      characteristics (occurrence, latency, duration) of the emesis elicited by
      apomorphine (200 micrograms/kg i.v.). In contrast, in conscious animals, naloxone
      (0.02 mg/kg i.v.) increased both the number and the duration (but not latency) of
      vomiting induced by a lower dose of apomorphine (30 micrograms/kg i.v.). These
      data show that apomorphine-induced vomiting and arterial hypotension do not
      involve opiate receptors.

PMID- 7711466
TI  - Observations on the arterial baroreflex in neurally mediated vasodepressor
      syncope.
AB  - The arterial baroreflex was studied in subjects who had recently had an episode
      of vasodepressor syncope. This was determined using 2-3 mcg/kg intravenous
      boluses of phenylephrine and assessing the bradycardic response. The values were
      measured in ms/mmHg and expressed as the angular coefficient of the regression
      line between the increase in R-R interval on the electrocardiograph and the
      systolic arterial pressure. In subjects examined immediately after the
      vasodepressor syncope episode the bradycardic response was much more marked than
      in controls (p < 0.01) and in the subjects themselves 6 months after the episode,
      provided that they were symptom-free (p < 0.01). It is concluded that in
      vasodepressor syncope there is a phase in which the baroreflex is highly
      sensitive and that this is due not to a lowering of the stimulation threshold but
      to a gain in the efferent arc, which explains a 'vagotonic' response.

PMID- 7711467
TI  - Atrial natriuretic peptide response to postural change and medication in familial
      dysautonomia.
AB  - Circulating atrial natriuretic peptide (ANP) was assayed before and after
      postural change and exercise in 54 patients with familial dysautonomia (FD) and
      20 controls. ANP levels were compared with blood pressure, heart rate, plasma
      catecholamines and parameters of renal function. Compared with controls supine FD
      subjects had elevated blood pressures, heart rates and ANP levels (39 +/- 4 pg/ml
      vs. 23 +/- 3 pg/ml, p < 0.01). With the erect posture and exercise in FD
      subjects, blood pressure fell below control values, with ANP lowered. In FD
      subjects, blood pressure was correlated with ANP levels when supine and when
      erect and with heart rate post exercise. In controls, ANP levels did not
      correlate with other parameters. In FD patients on metoclopramide, supine and
      erect blood pressure and ANP levels were higher. FD subjects treated with
      fludrocortisone, had elevated supine and erect noradrenaline (p < 0.05 and p =
      0.06); and those on diazepam had lower erect and post exercise noradrenaline (p <
      0.05), but ANP levels were similar. In conclusion, sympathetic denervation may
      increase FD patients' responsiveness to other regulators of cardiovascular
      integrity, such as ANP. In addition, circulating ANP and catecholamines in FD
      subjects appear to be influenced by commonly used medications, such as
      metoclopramide.

PMID- 7711468
TI  - Predictors of the pressor response to the clinic visit in essential hypertensives
      with and without diabetes mellitus.
AB  - Predictive models for the pressor response to the outpatient clinic visit (PRC)
      in essential hypertensives with and without diabetes are proposed. The hypotheses
      are derived from previous studies about the univariate correlates of this
      response. PRC was measured with ambulatory monitors. Twenty-four hour blood
      pressures and average PRCs were similar in the two groups. Diabetics had faster
      24-h heart rates, decreased heart rate variability, a broader range of PRCs and
      more depressor responders. PRC of nondiabetics correlated with duration of
      hypertension and was dependent on race; the predictive model had R2 of 0.19. In
      contrast, PRC of diabetics exhibited correlations with age, weight, BP and blood
      glucose and the model had R2 of 0.71. The data suggest that: diabetics had
      autonomic dysfunction, that their PRC can be modelled with predictors that are
      accepted correlates of autonomic neuropathy, and that these predictors attenuated
      PRC or its buffering. If these results were confirmed by prospective application
      of the model to a larger group of patients, 'true' blood pressures could be
      estimated by subtraction of predicted PRC from office blood pressures in
      diabetic, but not in nondiabetic, hypertensive patients.

PMID- 7711470
TI  - Indocyanine green video-angiographic findings in choroidal osteoma.
AB  - Indocyanine green video-angiography (ICG) was done twice on three patients with
      choroidal osteoma. Choroidal osteoma consisted of two portions, a yellow-white
      area and a surrounding orange area. The early phase of ICG angiography showed
      hypofluorescence due to blockage, corresponding to the osteoma. However, the
      hypofluorescence was greater in areas corresponding to the orange portions of the
      lesions than in the yellow-white parts. In the late phase, tumor staining was
      present, corresponding to the orange area. Although long-standing yellow-white
      lesions blocked fluorescence in the late phase, some of these showed
      hyperfluorescence. ICG video-angiography showed areas of blocked fluorescence in
      the early phase as well as hyperfluorescent areas accompanied by several small
      hypofluorescent foci in the late phase, corresponding to very slight
      ophthalmoscopically observed changes in the vicinity of the osteoma. During
      follow-up observation, fluorescein angiography confirmed the extension of the
      osteoma into this area. These results confirm that the characteristic findings of
      choroidal osteoma can be observed with ICG video-angiography. This imaging
      technique showed the lesions were larger than they appeared with ophthalmoscopy
      and fluorescein angiography.

PMID- 7711471
TI  - Interocular visual-field and intraocular-pressure asymmetries in normal-tension
      glaucoma.
AB  - To evaluate the role of intraocular-pressure (IOP) in the pathogenesis of
      glaucomatous damage in normal-tension-glaucoma, we investigated whether the eye
      with the higher IOP had more severe visual-field damage in 23 normal-tension
      glaucoma patients. Twelve patients did have more severe visual-field defects in
      the eye with the higher IOP, but 11 had more severe defects in the eye with the
      lower IOP. There was no correlation either between IOP and visual-field damage (r
      = 0.16; p = NS) or between the interocular differences in IOP and in visual-field
      damage (r = 0.21; p = NS). Thus, although intraocular pressure may contribute to
      glaucomatous damage even in normal-tension-glaucoma patients, other factors must
      be involved as well.

PMID- 7711469
TI  - Pupillary abnormalities due to sympathetic dysfunction in different forms of
      idiopathic headache.
AB  - Idiopathic vascular-type headache is frequently associated with pupillary
      alteration, which is often presumed to be due to malfunction of the sympathetic
      nervous system. In this review the anatomical and neurotransmitter basis of
      oculosympathetic function is briefly discussed along with some of the common
      pharmacological and physiological pupillary tests used in its assessment. The
      clinical and subclinical features of the pupil abnormalities are analysed in
      idiopathic headache, which includes migraine, tension headache, cluster headache,
      and chronic paroxysmal hemicrania. Possible mechanisms underlying these
      alterations are suggested. Among secondary headaches, carotid dissection and
      aneurysm have to be excluded when unilateral headache is associated with a
      persistent ipsilateral oculosympathetic deficit. From the literature, specific
      responses to pupillary tests apparently are present in idiopathic headache.
      Pupillary tests may differentiate between the subtypes of idiopathic headache.
      The investigation of pupillary dysfunction may provide information on the
      physiopathological basis of headache.

PMID- 7711472
TI  - Stimulation of penetrating corneal wound healing by exogenous fibronectin.
AB  - The paper describes the effect of exogenous fibronectin administered by
      instillation on the repair of the rabbit cornea after experimental mechanical
      injury. The effect was monitored by light microscopy and radioautography.
      Fibronectin had a beneficial effect on regenerating corneal epithelium,
      endothelium and keratocytes through a stimulatory effect on cell migration,
      proliferation and differentiation.

PMID- 7711473
TI  - Surgical results for proliferative vitreoretinopathy.
AB  - We reviewed 88 consecutive eyes that underwent vitrectomy for retinal detachment
      with proliferative vitreoretinopathy (PVR) and were followed a minimum of six
      months. A primary goal of the surgery was the meticulous trimming of the vitreous
      base in hopes of decreasing the incidence of post-operative reproliferation and
      anterior PVR. Those eyes with anterior PVR had aggressive release of vitreous
      base contraction (anteroposterior and circumferential) with intraocular scissors.
      All posterior tractional membranes were removed. All eyes received long-acting
      gas for postoperative retinal tamponade. Macular reattachment was achieved in 78
      (88.6%) eyes. Forty-six (52.3%) obtained at least 5/200 vision. Seventeen (19%)
      eyes were re-operated at least once. We compared the importance of initial lens
      status (pseudophakic, aphakic, phakic), need for relaxing retinotomy, presence of
      anterior PVR, and history of previous vitrectomy on the anatomic and visual
      results. No single factor was responsible for a statistically significant effect
      on either vision or anatomic success, except for the need for a relaxing
      retinotomy, which carried with it a decreased chance of an eye obtaining 5/200
      vision (Fisher's exact test, p = 0.03).

PMID- 7711474
TI  - Prognostic value of preoperative flash and pattern visual evoked potentials for
      diabetic retinopathy vitrectomy.
AB  - In view of the continuing controversy about the prognostic value of preoperative
      visual evoked potentials in diabetic vitrectomy, we retrospectively studied 31
      eyes undergoing vitrectomy for diabetic retinopathy after recording pattern
      and/or flash visual evoked potential recording. Preoperative pattern visual
      evoked potentials were of no prognostic value in these eyes but a decrease in the
      amplitude of preoperative flash visual evoked potentials was significantly
      correlated with unchanged or worsened postoperative visual acuity when compared
      with preoperative visual acuity (P = 0.0156, Fisher's exact test). Therefore,
      while acknowledging that diabetic vitrectomy functional prognosis is actually
      multifactorial, we still recommend recording preoperative flash visual evoked
      potentials for diabetic patients in whom significant opacities of the intraocular
      media preclude correct examination of the ocular fundus, because a decrease in
      peak III amplitude may indicate a guarded vitrectomy functional prognosis.

PMID- 7711476
TI  - Individual measurements of angiotensin II concentrations in aqueous humor of the
      eye.
AB  - The presence of constituents of the renin-angiotensin system (RAS) in ocular
      tissues and fluids suggests this system is involved in ocular physiology.
      Angiotensin II (AngII) is the main biological effector of the system, so we
      measured AngII in plasma and in aqueous humor of the anterior ocular chamber of
      patients undergoing cataract extraction. Untreated normotensive patients were
      compared with arterial hypertensive patients taking either diuretics which
      stimulate the RAS or angiotensin converting enzyme (ACE) inhibitors which reduce
      the production of AngII. Plasma levels of AngII were higher in patients on
      diuretics (5.46 +/- 1.04 fmol/ml; mean +/- SEM) than in untreated cataract
      patients (2.28 +/- 0.32 fmol/ml, p < 0.02), and were very low with ACE inhibitors
      (0.51 +/- 0.18 fmol/ml). In aqueous humor, AngII was measurable in 7 of 11
      patients on diuretics (median 1.1 fmol/ml), and in 6 of 16 normotensive patients
      (median < 0.55 fmol/ml), but not in aqueous humor of 4 patients receiving
      enalapril or captopril. These results demonstrate the presence of AngII in the
      eye but do not exclude either its sequestration in the eye or local production.
      The possibility of individual measurements of intraocular AngII will permit more
      precise determination of its role in future studies.

PMID- 7711475
TI  - Intermediate uveitis: what is the natural course of the disease and its
      relationship with other systemic diseases?
AB  - This study examined the natural course of intermediate uveitis, to find a
      possible correlation with systemic diseases and to identify the ocular
      complications. Patients were classified according to follow-up time in three
      groups: A (1-5 years) 12 pts, B (6-10 years) 10 pts, C (11-15 years or more) 6
      pts for a total of 28 patients (52 eyes). We studied the recurrences, the
      complications of the disease and the overall prognosis. Eight patients were found
      to be suffering from systemic diseases: sarcoidosis 2, Adamantiades-Behcet 2,
      multiple sclerosis 3 and Lyme disease 1. Cataract was found in 21 eyes (40.5%)
      and macular changes in 20 eyes (38.4%) but chronic cystoid macular edema
      persisted in only six cases (12.5%). Group C presented more complications than
      group B. Group A had the fewest. The frequency of recurrences was 1-5 for group
      A. 1-3 for group B and 1-2 for group C. Four patients received no therapy, 15
      received steroids and nine received cyclosporine and steroids. In this series
      intermediate uveitis was bilateral in 85.8% of patients and related with systemic
      diseases in 28.5%. Recurrences appeared mainly during the first five years. The
      longer the presence of the disease the more frequent were complications and the
      final visual acuity depended mostly on the severity of the initial attack and the
      number of exacerbations.

PMID- 7711478
TI  - Meeting of the European Association for the Study of Diabetic Eye Complications
      (EASDEC). Turin, September 25-26, 1994. Abstracts.

PMID- 7711477
TI  - Sinonasal undifferentiated carcinoma invading the orbit.
AB  - Sinonasal undifferentiated carcinoma (SNUC) is an infrequent tumor described by
      Frierson et al. in 1986. Since its initial description, fewer than 100 patients
      have been reported. We present a case of a SNUC invading the orbit in a 57-year
      old woman, for which the findings are documented by CT scan, light and electron
      microscopy.

PMID- 7711479
TI  - Cost-effective inpatient care of neuropsychiatric patients.
AB  - Managed care has decreased the frequency of hospitalization for psychiatric
      disorders, and it may have an especially strong impact on neuropsychiatric
      patients. The use of targeted, cost-effective interventions improves the quality
      of patient care and can assist with approval of funding for inpatient care by
      utilization review agencies.

PMID- 7711480
TI  - A proposed mechanism of emotion. 1937.

PMID- 7711481
TI  - Compulsive disorder and acquired antisocial behavior in frontal lobe dementia.

PMID- 7711482
TI  - Discontinuing anticonvulsant treatment of aggression.

PMID- 7711483
TI  - The need to evaluate functional status in diagnosing dementia.

PMID- 7711484
TI  - Anticoagulant therapy for dementia.

PMID- 7711485
TI  - Speculations regarding the course of recurrent affective disorder.

PMID- 7711487
TI  - Apathy: a treatable syndrome.
AB  - Apathy occurs frequently in neuropsychiatric disorders both as a symptom of other
      syndromes and as a syndrome per se. Histories are presented of patients with a
      syndrome of apathy who showed clinically significant, sustained benefit from
      pharmacological treatment. Etiologies included non-Alzheimer's frontal lobe
      dementia, cerebral infarction, intracranial hemorrhage, alcoholism, and traumatic
      brain injury. Agents included amantadine, amphetamine, bromocriptine, bupropion,
      methylphenidate, and selegiline. These histories support the suggestion that
      apathy is a discriminable dimension of behavior having its own pathophysiology
      and implications for psychiatric care. They raise the possibility of treatment
      for many patients previously thought untreatable. Studying the treatment of
      apathy may contribute to the clinical care and scientific understanding of
      neuropsychiatric disorders throughout the life span.

PMID- 7711486
TI  - Focal cerebral blood flow change during craving for alcohol measured by SPECT.
AB  - To test the hypothesis that craving for alcohol in the alcohol-dependent
      individual is mediated by a limbic circuit involving the caudate nuclei, regional
      cerebral blood flow was measured with [99mTc]HMPAO SPECT during control and
      craving conditions in 9 alcohol-dependent subjects. In all subjects, blood flow
      in the head of the right caudate nucleus increased during the craving condition,
      and these blood flow increases were strongly correlated with the experimentally
      induced increases in craving for alcohol. These new findings suggest a functional
      role for the limbic striatum in the mediation of craving and impaired control
      over alcohol consumption.

PMID- 7711488
TI  - Improvement in depression-related cognitive dysfunction following ECT.
AB  - Long-term cognitive changes were observed in 8 depressed patients whose
      pretreatment cognitive impairment (depressive dementia or pseudodementia)
      resolved after treatment with ECT. Improved performance on the Mattis Dementia
      Rating Scale was maintained throughout a 4-year follow-up period. Improvements on
      Memory and Initiation and Perseveration subscales were most consistent over time.
      These aspects of cognitive functioning may be the most susceptible to the effects
      of depression, and this may be a factor to consider in clinically evaluating
      older patients with both depression and cognitive impairment. The findings
      indicate that elderly patients with cognitive dysfunction secondary to depression
      may experience improvement in cognitive functioning that is stable over time with
      remission of the affective disorder.

PMID- 7711489
TI  - Magnetic resonance imaging of the corpus callosum: predictors of size in normal
      adults.
AB  - Eighty normal adults were studied with MRI to investigate the relationship
      between regional morphology of the corpus callosum and characteristics such as
      age, gender, education, and cranial size. The variability coefficient was 20% in
      total callosal area and from 19% to 40% in regional callosal area. Increasing age
      and smaller cranial area were both associated with smaller total and regional
      callosal areas; there were no effects of gender and education. The relative
      effects of age and cranial size varied across regions and were most prominent for
      anterior subdivisions. However, age and cranial size together explained less than
      half the variance in regional callosal size. Further study is needed to identify
      additional correlates of regional callosal anatomy.

PMID- 7711490
TI  - Ventricular dilation, cortical atrophy, and neuropsychological outcome following
      traumatic brain injury.
AB  - Day-of-injury computed tomographic scans were compared with postinjury magnetic
      resonance imaging of 38 patients with traumatic brain injury. Ventricles and
      several white and gray matter structures were measured. Results demonstrated
      significant changes in ventricular sizes and all measures of white matter.
      Changes in gray matter were nonsignificant, except in the putamen/globus
      pallidus. Patients were grouped according to ventricular change, and
      neuropsychological outcome was examined. The group with the highest ventricular
      change had significantly lower memory scores but did not show significant
      differences on tests of intellectual functioning. A three-dimensional image
      analysis was performed to enhance visualization of the injured brain.

PMID- 7711491
TI  - MRI abnormalities in major psychiatric disorders: an exploratory comparative
      study.
AB  - MRI scan reports from 536 psychiatric inpatients in 10 DSM-III-R diagnostic
      categories and 51 normal control subjects were reviewed for incidence and
      severity of four types of abnormality: deep white matter hyperintensities,
      periventricular hyperintensities, ventricular enlargement, and cortical atrophy.
      Multivariate analysis revealed significant effects for both diagnosis and age and
      a significant interaction. After age covariance, the most discriminant type of
      abnormality was ventricular enlargement, with normal control subjects having
      significantly less enlargement than 6 of 10 patient groups, including the
      personality disorder and the depressed nonpsychotic groups. The data also
      suggested important diagnosis by age by type-of-abnormality interactions
      deserving of further study.

PMID- 7711492
TI  - Positive and negative neuropsychiatric features in Alzheimer's disease.
AB  - Positive neuropsychiatric features (paranoia, delusions, hallucinations) and
      negative features (disinterest/withdrawal, apathy, reduced speech output, reduced
      physical activity) occur in Alzheimer's disease (AD), although most studies have
      focused on positive features alone. Positive features may be associated with a
      more severe and rapidly progressive subtype of AD. A retrospective analysis of
      prospectively obtained research data (101 probable AD patients) revealed that
      patients with positive features had been ill longer but were otherwise similar to
      patients with negative features. Patients with any neuropsychiatric features had
      more rapid progression and more severe cognitive and comprehension deficits than
      patients without such features. Neuropsychiatric features in AD likely reflect
      variations in mesocortical and mesolimbic degeneration rather than an etiologic
      or prognostic subtype.

PMID- 7711493
TI  - Phenylethylamine modulation of affect: therapeutic and diagnostic implications.
AB  - A review of the literature indicates that brain phenylethylamine (PEA) may be a
      neuromodulator of aminergic synapses and that it promotes energy, elevates mood,
      and favors aggression. Phenylacetic acid, the main metabolite of PEA, is
      decreased in the biological fluids of depressed subjects and schizophrenic
      subjects and is increased in schizoaffective subjects. The administration of PEA
      or of its precursor L-phenylalanine improves mood in depressed patients treated
      with a selective monoamine oxidase B inhibitor. The authors speculate that
      studies of PEA metabolism may have diagnostic value and that PEA administration
      may be therapeutic in selected depressed patients.

PMID- 7711494
TI  - Quantified electroencephalographic correlates of neuropsychological deficits in
      Alzheimer's disease.
AB  - The authors examined relationships between quantified EEG (qEEG) variables and
      neuropsychological performance in 54 consecutive patients with probable
      Alzheimer's disease (AD). Patients were studied with qEEG and a
      neuropsychological battery that assessed memory, attention, verbal functions, set
      shifting abilities, and procedural learning. More severe memory, attention, and
      verbal deficits were significantly correlated with lower alpha relative power,
      and increased theta relative power was significantly correlated with poor set
      shifting abilities. No qEEG variables were significantly correlated with the
      procedural learning task. These correlations between deficits in specific
      cognitive domains and qEEG bands suggest that qEEG may have an important role in
      the investigation of the cognitive deficits in AD.

PMID- 7711495
TI  - Rate of information processing in patients with Wilson's disease.
AB  - This study investigated the rate of information processing, independent of motor
      speed, in neurologically affected Wilson's disease (WD) patients. Two scanning
      tasks based on the Sternberg item-recognition paradigm were administered to 17
      neurologically symptomatic WD patients and 17 normal control (NC) subjects.
      Although WD subjects do have longer response latencies than NC subjects, their
      rate of information processing is the same as the rate of the NC subjects. The
      longer response latencies are attributable to their motor deficits. The clear
      impact of motor impairment on test performance underlines the necessity for
      specialized assessment measures that can accurately reflect the cognitive
      abilities of motor-impaired patients. These findings suggest that Wilson's
      disease is not characterized by slowed information processing.

PMID- 7711496
TI  - Prenuptial seizures: a report of five cases.
AB  - The cases of 5 patients with seizures occurring the day of or shortly before
      their weddings are presented. Major life events may precipitate or exacerbate
      epileptic or nonepileptic seizures as a result of 1) missed medications, 2) sleep
      deprivation, 3) alcohol or concomitant medications, 4) hyperventilation, or 5)
      the emotional state directly or stress indirectly. Seizures occurring at times of
      psychological stress may be either neurological or psychiatric in origin. The
      physician treating patients with a new onset or exacerbation of seizures around a
      major life event must consider all of these factors in the evaluation.

PMID- 7711497
TI  - Validity and utility of the ADAS-L for measurement of cognitive and functional
      impairment in geriatric schizophrenic inpatients.
AB  - This study examined the usefulness of the Alzheimer's Disease Assessment Scale
      Late Version (ADAS-L) for assessing cognitive and behavioral impairment in
      geriatric schizophrenic patients. Subjects were 339 geriatric schizophrenic
      inpatients. Discriminant function analyses compared the Mini-Mental State
      Examination (MMSE) with the ADAS-L as independent variables predicting the level
      of impairment on the criterion measure, the Clinical Dementia Rating. The ADAS-L
      surpassed the MMSE at correctly distinguishing severe to profound impairment; the
      MMSE was superior for identifying absent or questionable impairment. Findings
      provide evidence for the concurrent validity of the ADAS-L as an instrument for
      measuring impairment in geriatric schizophrenic inpatients.

PMID- 7711498
TI  - Hearing loss and asymmetry in major depression.
AB  - To assess patterns of hearing loss and asymmetry in major depressive disorder
      (MDD), pure-tone and brief-click audiometric thresholds were measured in 59
      inpatients with MDD and 40 normal control subjects. For both tasks, patients had
      higher bilateral thresholds, with marked hearing loss for the highest pure-tone
      frequency. At lower frequencies, patients displayed significant asymmetry, with
      poorer hearing in the left ear. After ECT, patients maintained the bilateral
      hearing losses; however, the baseline asymmetry resolved. These findings suggest
      that bilateral hearing loss may be a stable characteristic in severe depression.
      Poorer left ear pure-tone hearing may be present during the depressed state. The
      baseline asymmetry in audiometric deficits suggests right-hemisphere dysfunction
      in severe MDD.

PMID- 7711499
TI  - Prolonged akinetic mutism due to multiple sclerosis.
AB  - A 25-year-old woman with multiple sclerosis and an affective disorder probably
      secondary to MS presented with multiple neurological signs and symptoms
      suggestive of active MS, most prominently akinetic mutism. Spinal fluid analysis
      and MRI supported a diagnosis of active MS. SPECT and EEG were nonspecifically
      abnormal. After 6 weeks of severe akinetic mutism refractory to one ECT treatment
      and trials of steroids and stimulants, the patient recovered spontaneously over a
      2-month period. An acute brainstem lesion seen on MRI may explain this patient's
      akinetic mutism.

PMID- 7711500
TI  - Schizophrenia may alter neuromagnetic representations of attention.
AB  - When male paranoid schizophrenic subjects attended to a dichotic oddball task
      requiring target discrimination, their 100-ms latency left hemisphere magnetic
      auditory sources did not increase in strength, and their source geometry appeared
      to be degraded, rather than enhanced, compared with normal control subjects,
      implicating abnormal processing in the superior temporal gyrus.

PMID- 7711501
TI  - Pathways to neuropsychiatry.

PMID- 7711502
TI  - Pretibial myxedema and high-dose intravenous immunoglobulin treatment.
AB  - Seven patients affected by Graves' ophthalmopathy and pretibial myxedema (four
      patients with nodular form, two with diffuse, and one with elephanthiasic form)
      have been treated with high-dose intravenous immunoglobulins. We have observed
      (a) clinical improvement of pretibial myxedema and Graves' ophthalmopathy in all
      patients, (b) a reduction of pretibial skin thickness, by ultrasonography
      evaluation, in four patients, (c) a reduction of mucopolysaccharide skin content
      in three patients, (d) disappearance of lymphocytic skin infiltration and IgG
      deposition in two patients, and (e) a parallel reduction of the titer of
      circulating autoantibodies as antithyroglobulin, antimicrosomal, anti-TSH
      receptor, and of non-organ-specific antibodies as antinuclear, anti-smooth muscle
      cells, and anti-mitochondrial. In comparison two patients with Graves'
      ophthalmopathy and pretibial myxedema treated with systemic corticosteroids did
      not present any improvement of the cutaneous ailment. Therefore, this study
      suggests that intravenous immunoglobulins are effective in the treatment of
      pretibial myxedema and may have an immunomodulant action in patients with Graves'
      disease and related disorders.

PMID- 7711503
TI  - Therapy of Graves' ophthalmopathy with intravenous high-dose steroid followed by
      orbital irradiation.
AB  - We investigated the effects of intravenous high-dose steroid therapy followed by
      orbital irradiation for Graves' ophthalmopathy in eight patients. All patients
      presented with diplopia or fixed globes. Extraocular muscle dysfunction showed
      excellent improvement after the combined therapy; diplopia disappeared completely
      in five of them, and one patient with fixed globes showed normal eye movement.
      Two other patients also exhibited great improvement, although their diplopia
      persisted. Their ophthalmopathy index was decreased from (mean +/- SD) 4.25 +/-
      0.82 to 0.75 +/- 1.48. Extraocular muscle enlargement, assessed by magnetic
      resonance imaging study after the radiotherapy, was also reduced after the
      combined therapy, although two patients did not show remarkable enlarged
      extraocular muscles. There was no change in extraocular muscle thickness 6-9
      months after the therapy, and the ophthalmopathy index did not show change in a
      long follow-up (maximum 37 months after the therapy). These results suggest that
      high-dose methylprednisolone followed by orbital radiotherapy is a good
      therapeutic design for Graves' ophthalmopathy and justify a prospective
      randomized trial.

PMID- 7711504
TI  - A high prevalence of human T-lymphotropic virus type I carriers in patients with
      antithyroid antibodies.
AB  - Human T-lymphotropic virus type I (HTLV-I) is a causative retrovirus of adult T
      cell leukemia lymphoma and HTLV-I associated myelopathy/tropical spastic
      paraparesis. HTLV-I is also associated with some forms of pulmonary alveolitis,
      chronic arthropathy, polymyositis, and uveitis. In this study, the possible role
      of HTLV-I infection in the pathogenesis of autoimmune thyroid diseases with
      positive antithyroid antibody (ATA) to microsomal antigen or thyroglobulin was
      evaluated. In Fukuoka Prefecture or the northern part of Kyushu Island located in
      the southwestern part of Japan, the prevalence of patients with HTLV-I antibody
      was screened using the particle agglutination test and then was further confirmed
      either by the indirect immunofluorescence method or the western blot method. The
      observed prevalence in patients with thyroid disorders and the estimated
      prevalence calculated considering the sex- and age-specific prevalence among
      healthy blood donors (n = 16,008) were as follows: 19 (7.4%) vs 7.8 (3.0%) (p <
      0.001) for ATA-positive chronic thyroiditis (n = 257), 21 (7.0%) vs 6.6 (2.2%) (p
      < 0.001) for ATA-positive Graves' disease (n = 298), 4 (4.3%) vs 2.1 (2.2%) (ns)
      for ATA-negative Graves' disease (n = 94), 1 (2.9%) vs 1.1 (3.1%) (ns) in ATA
      negative hypothyroidism (n = 35), and 3 (1.8%) vs 5.0 (2.9%) (ns) for ATA
      negative nodular goiter (n = 170). These findings thus suggest that HTLV-I
      infection may have some relationship to ATA-positive thyroid disorders.

PMID- 7711505
TI  - Thyroid peroxidase in dyshormonogenetic goiters with organification and
      thyroglobulin defects.
AB  - Thyroid peroxidase (TPO) iodide and guaiacol oxidation activities were evaluated
      in eight dyshormonogenetic goiters. Two of these had a defective thyroglobulin;
      the TPO iodide oxidation (431 and 316 U/g ptn) and iodination (31 and 8.6 nmol
      I/mg ptn) activities were within the normal ranges. The goiters from two siblings
      with positive perchlorate iodide discharge tests also had normal TPO iodide
      oxidation (602 and 299 U/g ptn) and iodination activities (44 and 11 nmol I/mg
      ptn). No TPO iodide oxidation activity was found in the goiters from the other
      four patients with positive perchlorate iodide discharge tests, and TPO iodide
      oxidation inhibitory activities were detected in both their TPO and thyroglobulin
      preparations. Three of them had some TPO guaiacol oxidation activity and did not
      inhibit normal guaiacol oxidation. The TPO preparation immunoblot of these three
      goiters showed a faintly visible band of normal 100 kDa TPO. However, in the
      other patient no guaiacol oxidation activity was detected, and only two bands of
      low-molecular-weight TPO (72 and 43 kDa) were found, again showing that iodine
      organification defects in dyshormonogenetic goiters can be due to either
      qualitative or quantitative TPO defects. The TPO inhibition diminished when
      iodide was increased in the assay, but was not altered by increasing cofactor
      (H2O2). Our results, so far, suggest that the TPO-inhibitory substance may
      interact reversibly with a specific iodide site on the enzyme or with the
      oxidized form of iodide, and/or could bind free iodide, making it unavailable for
      enzymatic oxidation.

PMID- 7711506
TI  - Octreotide therapy in advanced thyroid cancer.
AB  - Octreotide is a long-acting somatostatin analog that inhibits cell growth and
      hormone secretion. It has been successfully used in the management of a variety
      of endocrine tumors (i.e., acromegaly, carcinoid tumors, gastrinomas). In vitro,
      octreotide suppresses adenylate cyclase activity, DNA synthesis, and cell growth
      in cultured thyroid cell lines. Previous studies examining the use of octreotide
      in the treatment of medullary thyroid cancers, in vivo, report symptomatic
      improvement from tumor-related hormonal hypersecretion; however, octreotide's
      ability to suppress tumor growth was limited. In the present study, we examine
      the efficacy of long-term octreotide administration in six subjects with
      metastatic thyroid carcinoma, including Hurthle cell (one subject), medullary
      (one subject) and papillary or mixed papillary/follicular cancer (four subjects).
      All of the subjects had documented recurrences of their thyroid tumors despite
      appropriate therapy, and were considered to be untreatable by conventional
      therapeutic modalities (i.e., radioiodine or surgery). Subjects were monitored
      while receiving relatively high doses (4 mg daily) octreotide subcutaneously for
      up to 12 months. Octreotide therapy was very well tolerated; mild
      gastrointestinal symptoms persisted throughout treatment in one subject.
      Octreotide did not significantly decrease tumor markers (e.g., thyroglobulin,
      calcitonin, carcinoembryonic antigen). The carcinomas progressed during
      treatment, as evidenced by an increase in the size and/or number of metastatic
      lesions. In summary, in this small series subcutaneous octreotide administration
      did not appear to be efficacious in the management of advanced thyroid cancers.

PMID- 7711507
TI  - Thyroid cancer in pregnant women: diagnostic and therapeutic management.
AB  - There is considerable literature on the effect of pregnancy on established
      thyroid cancer. In contrast, there are only isolated case reports of management
      of thyroid cancer diagnosed de novo during pregnancy. We describe four such
      patients. We recommend fine-needle aspiration biopsy (FNA) of solitary thyroid
      nodules found early in pregnancy. When the cytopathology is diagnostic of thyroid
      cancer, thyroidectomy under local or general anesthesia is advised. The patient
      should be given levothyroxine in a dose sufficient to keep serum thyroid
      stimulating hormone (TSH) low. Serum thyroglobulin is a valuable noninvasive
      method of evaluating completeness of this therapy. The work-up of a nodule found
      late in pregnancy is best deferred until after delivery.

PMID- 7711508
TI  - Thyroid surgery using monitored anesthesia care: an alternative to general
      anesthesia.
AB  - Forty consecutive patients undergoing thyroid surgery under local anesthesia (LA)
      by a single surgeon over a 5-year period were included in this retrospective
      review. In all cases, the indication for LA was patient request. The study
      included 29 females and 11 males with an average age of 44 years (range 22-66
      years). Body habitus was thin in 12.5%, average in 67.5%, and obese in 20%.
      Operations consisted of 21 unilateral thyroid lobectomies, 3 partial
      thyroidectomies, 3 subtotal thyroidectomies, and 13 total thyroidectomies. The
      pathology revealed benign disease in 45% and malignant disease in 55%. All
      procedures were performed using lidocaine and/or bupivacaine to administer a deep
      cervical plexus block as well as a field block. Mild additional intraoperative
      intravenous sedation was provided in most cases. Two patients were converted
      emergently to general endotracheal anesthesia because of inability to tolerate LA
      in one and a seizure secondary to intraarterial injection of lidocaine in the
      other patient. There were no instances of wound infection hemorrhage, recurrent
      laryngeal nerve injury, or hypoparathyroidism. In conclusion, thyroid surgery in
      selected patients can be performed safely using LA by experienced surgeons. If
      patients are carefully prepared preoperatively, LA offers a simple and reasonable
      alternative to general anesthesia.

PMID- 7711509
TI  - Thyrotoxic hypokalemic periodic paralysis: report of four cases in black American
      males.
AB  - Thyrotoxic periodic paralysis (TPP) is an unusual complication of a fairly common
      disease affecting mostly Asian males. In the United States, there have been
      several reports of TPP in different ethnic populations and it appears that the
      incidence is approximately one-tenth of that found in Asian countries. Only six
      reports of TPP in African-Americans could be found in the literature; however, we
      are reporting four cases diagnosed within a 13-year period at our institution. We
      conclude that TPP may occur more often in Blacks than previously suspected and
      should be considered when patients present with unexplained hypokalemia, muscular
      weakness and rhabdomyolysis. The epidemiology, clinical manifestations,
      pathophysiology, and treatment of TPP are reviewed.

PMID- 7711510
TI  - Thyrotropin stimulation of the lutropin/choriogonadotropin receptor: different
      sites mediate agonist activity and high affinity binding.
AB  - Surprisingly, thyrotropin (TSH) can increase cAMP and inositol phosphate (IP)
      levels in Cos-7 cells transfected with the lutropin (LH)/choriogonadotropin (CG)
      receptor (LH/CGR) as well as LH or CG, as evidenced by similar EC50 and maximal
      stimulation values. Additionally surprising, TSH activation is evident, despite
      markedly reduced levels of high affinity TSH binding by comparison to CG (Hidaka
      A, et al. 1993 Biochem Biophys Res Commun 196:187-195). In this report, we
      questioned whether the unusual TSH activity, as well as the discrepancy between
      TSH activity and binding, might reflect the existence of distinct agonist and
      binding sites on the LH/CGR extracellular domain and the ability of TSH to
      interact with the former despite a minimal interaction with the latter. We
      evaluated this possibility by using two chimeras spanning the extracellular
      domain of the TSHR and the LH/CGR:Mc1 + 2, where residues 8-165 of the TSHR are
      substituted, and Mc2 + 3 + 4, where residues 90-370 are replaced with the
      corresponding peptide segment from the LH/CGR. After transfection in Cos-7 cells,
      Mc2 + 3 + 4 exhibits higher affinity for CG than wild-type LH/CGR, but has no CG
      agonist response in assays measuring cAMP or inositol phosphate (IP) levels.
      Conversely, the Mc1 + 2 chimera exhibits significantly decreased affinity for CG,
      but CG agonist activity is comparable to wild-type LH/CGR in cAMP and IP assays.
      These data show that the extracellular domain of the LH/CGR does have distinct
      sites for CG binding and agonist activity: the C-terminus in Mc2 + 3 + 4 is
      important for high affinity CG binding, whereas the N-terminus in Mc1 + 2 is able
      to exhibit a CG agonist response, despite low affinity binding. When evaluated
      using TSH, Mc1 + 2, with the C-terminus of the TSHR present, exhibits high
      affinity TSH binding comparable to wild-type TSHR. Unexpectedly, Mc1 + 2, with
      the substitution of the N-terminus of the extracellular domain of the LH/CGR,
      exhibits even better TSH agonist activity than wild-type TSHR, not a loss of
      activity. Thus, the N-terminus of the extracellular domain of the LH/CGR can
      couple TSH binding to signal transduction events even better than the N-terminus
      of the TSHR. This may, in part, explain why TSH has an unusual agonist activity
      in cells transfected with LH/CGR, despite relatively low affinity binding.
      Although distinct agonist and binding sites exist in the linear sequence of the
      extracellular domain, the activity of the two sites is interdependent.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7711511
TI  - Species differences of the thyroid protein kinase C heterogeneity.
AB  - Protein kinase C (PKC), the mediator of the phosphoinositide transduction
      pathway, is a family of at least 11 isozymes and its heterogeneity has been
      described in many tissues and cells. We studied here the heterogeneity of PKC in
      thyroid glands from three different species, rat, pig, and dog. By combining
      immunological and biochemical approaches, we identified in rat thyroids, the PKC
      alpha, beta II, delta, epsilon, and zeta subspecies, in pig thyroids, the alpha,
      epsilon, and zeta isozymes, and in dog thyroids, only the alpha and zeta
      isozymes. The observed species differences of the thyroid gland PKC heterogeneity
      could be related to the reported species differences in the activation of the
      phosphoinositide regulatory cascade by TSH and other thyroid cell regulators.

PMID- 7711512
TI  - Characterization of thyroid hormone effect on the visual system of the adult rat.
AB  - To characterize the effect of thyroid hormone on the central nervous system in
      adult rats, we recorded evoked potentials by photic (VEP) and electrical
      stimulation in normal, thyroidectomized (Tx) and T3- or T4-supplemented (Tx-T3,
      Tx-T4) male adult rats under pentobarbital anesthesia. The latencies of VEPs
      recorded in the visual cortex (VC) and lateral geniculate nucleus (LGN), and the
      b-waves of the electroretinograms (ERG) of these three groups were compared. A
      significant prolongation of the latency of VEP by photic stimulation (flash light
      intensity 2J, 0.2 Hz) in the VC was observed 14 to 28 days after thyroidectomy
      (27.9 +/- 0.4 vs. 33.4 +/- 0.43 msec, p < 0.01). Similar prolongations were also
      observed when those of the VEP in the LGN and the b-wave of the ERG were compared
      to those of normal rats (22.4 +/- 0.37 vs. 27.3 +/- 0.41 msec, p < 0.01; 21.8 +/-
      0.21 vs. 25.3 +/- 0.41 msec, p < 0.01, respectively). The prolonged latencies
      observed in the VC, LGN, and ERG-b-wave were partially normalized 24 hr after T3
      supplement (50 micrograms/kg, sc) and fairly restored to normal levels by 48 hr
      after T4 injection (100 micrograms/kg sc). The VEP latencies in the LGN and VC
      showed a positive correlation with the b-wave latency of the ERG in these three
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711513
TI  - Studies on the action of thyroid stimulation blocking antibody (TSBAb) on thyroid
      cell membrane.
AB  - The effect of thyroid stimulation blocking antibody (TSBAb) on stimulated cyclic
      AMP (cAMP) production induced by adenylate cyclase stimulators in porcine thyroid
      membrane (PTM) and porcine thyroid cells (PTC) has been studied. Ten TSBAbs with
      high TSH binding inhibitory immunoglobulin (TBII) activities significantly
      blocked TSH-stimulated cAMP production in PTC. The blocking effect of TSBAb on
      the cAMP increase induced by forskolin or GTP-gamma S stimulation in PTC was
      found in a few cases. However, there was no blocking action of TSBAb on the cAMP
      increase stimulated by forskolin, GTP gamma S, or NaF in isolated PTM. When TSBAb
      globulin was absorbed with PTM or guinea pig epididymal fat membrane (GPFM), the
      TBII activity in TSBAb-globulin was significantly absorbed by these membranes. A
      decrease of TSBAb activity (blocking activity for TSH-stimulated cAMP production
      in PTC) by PTM absorption, but no decrease by GPFM absorption, was found in six
      cases. This suggests that the potent TSBAb-neutralizing component may be
      associated with a non-TSH receptor site in the thyroid membrane. The other four
      cases showed a decrease of TSBAb activity by absorption with both PTM and GPFM.
      This suggests that the TSBAb-neutralizing activity may be associated with the TSH
      receptor site of both PTM and GPFM. The results of the present study suggest that
      TSBAb may block TSH action either via the TSH receptor itself or via a non-TSH
      receptor component of the thyroid membrane and not at a postreceptor level.

PMID- 7711514
TI  - Mechanisms by which thyroid hormone receptor mutations cause clinical syndromes
      of resistance to thyroid hormone.
AB  - Resistance to thyroid hormone (RTH) is an autosomal dominant disorder that is
      caused by mutations in the thyroid hormone receptor beta (TR beta) gene. The
      thyroid hormone receptor is a nuclear receptor that acts by binding to DNA to
      stimulate or repress gene transcription. Mutations that cause RTH are clustered
      within two regions of the hormone binding domain of the receptor. These mutations
      reduce thyroid hormone binding in most cases, but preserve the ability of the
      receptor to dimerize and to bind to DNA. Consequently, the mutant receptors are
      thought to occupy DNA target sites as inactive complexes that are not capable of
      activation by hormone. Not only are RTH mutants inactive, but they function in a
      dominant negative manner to block the access of normal receptors to thyroid
      hormone responsive genes. The mechanism of dominant negative activity and the
      relationship of genotype and phenotype remain active areas of investigation.

PMID- 7711515
TI  - The potential immunological role of the thyroid cell in autoimmune thyroid
      disease.
AB  - Over the last decade it has become evident that thyroid follicular cells express
      a number of immunologically active molecules in autoimmune thyroid disease that
      may endow them with the capacity to interact with cells of the classical immune
      system. Expression of major histocompatibility complex class II molecules is
      induced by gamma-interferon, but there is no evidence yet that thyroid follicular
      cells can concurrently express the costimulatory signals necessary for class II
      expression to result in T cell stimulation: in this situation, class II
      expression may have a protective role, inducing T cell anergy. Thyroid follicular
      cells also express a variety of cell surface proteins (in particular CD59) that
      may protect the cells from complement attack. On the other hand, the expression
      of adhesion molecules and cytokines by thyrocytes would seem to be harmful, as
      these are likely to exacerbate autoimmune injury. Further study of the
      immunological role of thyroid follicular cells will shed new light on the
      pathogenesis of Graves' disease and autoimmune hypothyroidism, and may lead to
      novel therapeutic approaches to these disorders.

PMID- 7711516
TI  - Management of patients with differentiated thyroid cancer who have positive serum
      thyroglobulin levels and negative radioiodine scans.
AB  - Most current evidence suggests that patients with papillary or follicular thyroid
      cancer after total thyroidectomy who are Tg positive (Tg > or = 10 ng/mL) and
      radioactive iodine scan negative warrant treatment with 100 mCi of 131I with a
      follow up scan and Tg determination. If isolated focal metastatic deposits are
      present they should be resected before treatment with radioiodine. Although some
      physicians might recommend radioiodine treatment only for high risk patients, we
      would recommend it for all patients with elevated serum Tg levels that increase
      after TSH stimulation, or until further information becomes available to support
      a different approach.

PMID- 7711517
TI  - Thyroid hormone and bone.

PMID- 7711518
TI  - Thyroid hormone binding to isolated human apolipoproteins A-II, C-I, C-II, and C
      III: homology in thyroxine binding sites.

PMID- 7711519
TI  - European semi-anthropomorphic phantom for the cross-calibration of peripheral
      bone densitometers: assessment of precision accuracy and stability.
AB  - A semi-anthropomorphic 'distal radius like' phantom, developed by Kalender and
      Ruegsegger for use in peripheral bone densitometry using single photon (DPA) dual
      X-ray (DXA) and quantitative computed tomography (QCT) machines, has been studied
      with a view to cross-calibrating different types and brands of densitometers in
      current use. In the context of an EU 'Concerted Action' (second Framework
      Programme) the phantom was repeatedly measured on six SPA machines, three DXA
      machines and nine QCT machines (545 measurements). Linear regression equations
      were derived, individual to each machine, which allowed the derivation of
      'standardized densities'. In this way we converted measurements made by machines
      of the same modality to a common scale of measurements. Two machines (one DXA,
      one SPA) showed statistically significant instability over time emphasising the
      need for rigorous quality control in the application of densitometry. In other
      respects these results provide an encouraging basis for the derivation of
      standardized normative ranges and the more effective use of peripheral
      densitometry in future clinical and epidemiological studies.

PMID- 7711520
TI  - Determination of bioactive rat parathyroid hormone (PTH) concentrations in vivo
      and in vitro by a 2-site homologous immunoradiometric assay.
AB  - A new homologous 2-site assay for rat parathyroid hormone (IRMA), developed by
      Immutopics, Inc., has been evaluated and compared with a bone cell cAMP bioassay.
      Circulating PTH for adult rats assayed with this IRMA are in the range 10-15
      pg/ml, and of the same order of magnitude as published values for biologically
      active PTH. The standard curve for the IRMA was linear over the range 3.4-240
      pg/ml of rPTH 1-34, and serum samples diluted in parallel with the standard
      curve. The within-assay and between-assay coefficients of variation ranged from
      5.2% (n = 18) to 7.6% (n = 24) and 8.3% (n = 16) to 26.4% (n = 10), respectively.
      Serum PTH values (mean +/- S.E.) for parathyroidectomized rats were 3.5 +/- 0.6
      pg/ml (n = 18) versus 10.3 +/- 1.4 pg/ml (n = 16) for intact non-mated rats.
      Calcium injections suppressed circulating PTH by 50%. Lactating rats had serum
      PTH levels 5-fold higher and vitamin D deficient rats 60-fold higher than non
      mated controls. PTH secreted from parathyroid cells in vitro was in the range 60
      490 pg/ml as determined by the IRMA. These values represented 86.0 +/- 9.0% of
      the comparable bioassay values, indicating that the IRMA detects only bioactive
      PTH.

PMID- 7711521
TI  - WBN/Kob rat: a new model of spontaneous diabetes, osteopenia and systemic
      hemosiderin deposition.
AB  - A long-term investigation of bone mineral metabolism in a newly developed strain,
      the WBN/Kob rat, which spontaneously develops diabetes, possibly due in part to
      hemosiderin deposition, was conducted. WBN/Kob rats used in this study developed
      diabetes after 9 months of age. Bone mass peaked at 6 months or 8 months of age,
      and femoral breaking strength was maximal at 8 months of age, declining rapidly
      after the development of diabetes. In contrast, both the bone mass and the
      mechanical strength increased up to 14 months of age in controls. The serum
      osteocalcin (BGP) levels were lower at 4 months of age and serum 1.25(OH)2D
      levels were significantly lower throughout the study in WBN/Kob rats than in
      controls. These results suggest that abnormal bone and mineral metabolism is
      present in WBN/Kob rats before the onset of diabetes, and that bone strength and
      BMD decrease simultaneously with the development of diabetes. This strain can
      serve as a useful model, not only of hemosiderosis and diabetes, but also of
      osteopenia.

PMID- 7711522
TI  - The effect of dietary calcium content and oral vitamin D3 supplementation on
      mineral homeostasis in a subterranean mole-rat Cryptomys damarensis.
AB  - The Damara mole-rat, Cryptomys damarensis, has no access to obvious dietary or
      endogenous sources of vitamin D. We tested the hypotheses that mineral metabolism
      in these animals is independent of vitamin D status but rather is affected by
      dietary calcium (Ca) content. Furthermore, we questioned whether bone and teeth
      assist in plasma mineral homeostasis. Mole-rats increased Ca intake when dietary
      Ca content increased; however, mode of gastrointestinal uptake, vitamin D
      metabolite and plasma Ca concentrations were not altered. Similarly, oral vitamin
      D supplementation did not affect gastrointestinal Ca absorption or alter plasma
      Ca concentration, although significant increases in plasma concentrations of
      vitamin D were evident. Bone and teeth mineral (Ca and Pi) content were augmented
      with vitamin D supplementation. Mineral homeostasis was primarily maintained by
      manipulating mineral deposition in teeth, for mineral content in teeth increased
      significantly when dietary Ca content changed from 1.3 g/kg to 2.6 g/kg and
      higher. Mineral homeostasis in these subterranean rodents does not appear to be
      regulated at the level of the intestine, but rather by manipulating bone and
      teeth mineral reservoirs.

PMID- 7711523
TI  - A pharmacological assessment of the mammalian osteoclast vacuolar H(+)-ATPase.
AB  - It is well established that osteoclasts use a vacuolar-type H(+)-ATPase (V
      ATPase) for proton pumping during bone resorption and that specific V-ATPase
      inhibitors such as bafilomycin A1 abolish osteoclastic bone resorption in the
      bone slice assay. It has been reported that the V-ATPase in avian osteoclasts can
      be distinguished from the V-ATPase expressed in most other cells, by virtue of
      its inhibition by vanadate and nitrate ions. In order to determine whether the V
      ATPase in mammalian osteoclasts can be similarly distinguished, we have
      investigated the effects of vanadate and nitrate on bone resorption by rat
      osteoclasts in the bone slice assay, in comparison with known V-ATPase
      inhibitors, bafilomycin A1 and WY 47766, that also inhibit the chicken osteoclast
      V-ATPase. The results indicate that, unlike the avian osteoclast V-ATPase, the
      mammalian osteoclast V-ATPase is pharmacologically similar to the V-ATPase in
      other cells.

PMID- 7711524
TI  - Waiting times and the patient's charter.

PMID- 7711525
TI  - Postmarketing surveillance.

PMID- 7711526
TI  - Service increment for teaching and research.

PMID- 7711527
TI  - Rationing intensive care.

PMID- 7711528
TI  - Pulling the plug on futility.

PMID- 7711529
TI  - Metered dose inhalers free of chlorofluorocarbons.

PMID- 7711530
TI  - Follow up in breast cancer.

PMID- 7711531
TI  - Rationing: the debate we have to have.

PMID- 7711532
TI  - Professor banned from transfusion building.

PMID- 7711533
TI  - Search for HIV vaccine faces setback.

PMID- 7711534
TI  - Chemical weapons did not cause the Gulf war syndrome.

PMID- 7711535
TI  - Cross sectional study of effects of drinking green tea on cardiovascular and
      liver diseases.
AB  - OBJECTIVE: To investigate the association between consumption of green tea and
      various serum markers in a Japanese population, with special reference to
      preventive effects of green tea against cardiovascular disease and disorders of
      the liver. DESIGN: Cross sectional study. SETTING: Yoshimi, Japan. SUBJECTS: 1371
      men aged over 40 years resident in Yoshimi and surveyed on their living habits
      including daily consumption of green tea. Their peripheral blood samples were
      subjected to several biochemical assays. RESULTS: Increased consumption of green
      tea was associated with decreased serum concentrations of total cholesterol (P
      for trend < 0.001) and triglyceride (P for trend = 0.02) and an increased
      proportion of high density lipoprotein cholesterol together with a decreased
      proportion of low and very low lipoprotein cholesterols (P for trend = 0.02),
      which resulted in a decreased atherogenic index (P for trend = 0.02). Moreover,
      increased consumption of green tea, especially more than 10 cups a day, was
      related to decreased concentrations of hepatological markers in serum, aspartate
      aminotransferase (P for trend = 0.06), alanine transferase (P for trend = 0.07),
      and ferritin (P for trend = 0.02). CONCLUSION: The inverse association between
      consumption of green tea and various serum markers shows that green tea may act
      protectively against cardiovascular disease and disorders of the liver.

PMID- 7711536
TI  - Adult outcome of normal children who are short or underweight at age 7 years.
AB  - OBJECTIVES: To evaluate the adult growth outcome (at age 23) of children who are
      short or underweight at age 7 years in whom no identifiable pathological cause
      exists for their poor growth. DESIGN: Longitudinal follow up of a birth cohort.
      SETTING: The national child development study (1958 birth cohort) of Great
      Britain. SUBJECTS: 523 children with a height or a weight below the fifth centile
      at age 7. Of these, 70 (13.4%) were excluded because they had a longstanding
      illness that could account for their poor growth. The remaining 453 subjects, who
      were followed to age 23, provided the base group from which those with additional
      data, such as parental height, were obtained. RESULTS: 55/174 (31.6%) boys who
      were short at age 7 became short men; 60/211 (28.4%) girls who were short at age
      7 became short women. Among boys who were underweight at age 7, 46/160 (28.7%)
      were still underweight at age 23, while 61/200 (30.5%) girls underweight at age 7
      became underweight women. Having short parents did not increase the probability
      of being small as an adult. Children with delayed puberty were as likely to
      remain small as those in whom puberty was not delayed. CONCLUSIONS: One in three
      normal children who was short or underweight at age 7 became a short or
      underweight adult. This informs the management of short children and may be
      valuable when prolonged growth hormone treatment for short stature is being
      considered.

PMID- 7711538
TI  - Abnormal liver growth in utero and death from coronary heart disease.

PMID- 7711537
TI  - Insulin dependent diabetes in children under 5: incidence and ascertainment
      validation for 1992.
AB  - OBJECTIVE: To establish the incidence of insulin dependent diabetes diagnosed in
      children under 5 years of age in the British Isles during 1992, comparing the
      national and regional results with those of our 1988 national study, and
      estimating the 1992 study's level of case ascertainment. DESIGN: Active monthly
      reporting of cases by consultant paediatricians through the framework of the
      British Paediatric Surveillance Unit, with additional reports from specialist
      diabetes nurses and regional health authorities. SUBJECTS: All children diagnosed
      under the age of 5 years with primary insulin dependent diabetes from 1 January
      to 31 December 1992 (inclusive) and resident in the British Isles at diagnosis.
      RESULTS: 387 children (208 boys and 179 girls) were confirmed to have insulin
      dependent diabetes, giving a national incidence of 9.3/100,000/year. This is
      similar to the 9.9/100,000/year found in 1988. Three sample capture-recapture
      analysis, which could only be applied across the 12 (out of 18) regions supplying
      regional information to the study, suggested ascertainment rates of 78% for the
      British Paediatric Surveillance Unit, 67% for specialist nurses, 69% for regional
      health authorities, and 99% for the aggregated registry. CONCLUSIONS: The
      national incidence of diabetes in the under 5s in the British Isles did not
      differ between 1988 and 1992. Nearly complete (99%) ascertainment of cases was
      possible only for regions for which three data sources were available. Capture
      recapture analysis highlighted both the need for more than one data source and
      for each data source to be complete for the whole study area.

PMID- 7711539
TI  - Family doctors and change in practice strategy since 1986.
AB  - OBJECTIVES: To investigate the changes in practice strategy that have taken place
      since 1986. DESIGN: Comparison of practices in 1986 and 1992. SETTING: 93% of
      group practices (26 practices) in a single family health services authority. MAIN
      OUTCOME MEASURES: Changes in staffing, premises, equipment, clinic services, and
      incomes between 1986 and 1992. RESULTS: In 1986, 28% of practices employed a
      nurse; in 1992, 92% did so. Between 1986 and 1992, 14 cost-rent schemes costing
      more than 10,000 pounds had been started. Certain practices, designated
      innovators, were more likely to possess specified items of equipment than other
      practices. Computer ownership was widespread: 77% of practices had a computer,
      compared with 36% in 1986. In 1992, 16 practices had a manager, compared with 10
      in 1986. Clinic services provided by more than half of practices were well
      established services (antenatal, for example), new services for which a payment
      had been introduced (such as diabetes, asthma, minor surgery), or the more
      readily provided "new" clinic services (diet, smoking cessation). Gross income
      increased, but so did practice costs, especially for innovators. Practices in the
      more affluent area of the family health services authority were still more likely
      to invest in their premises and staff, and to provide more services than those in
      the declining area. In the more affluent area, practices had higher costs but
      also higher incomes. CONCLUSION: Between 1986 and 1992, practices in this area
      invested heavily in equipment and services, but differences remain, depending on
      the location of the practice. Investment has increased, particularly in the more
      deprived part of the area, so that the inconsistency in standards has been much
      reduced. Practice incomes have risen, but so also have workload and costs.

PMID- 7711540
TI  - Malaria prophylaxis: guidelines for travellers from Britain. Malaria Reference
      Laboratory of the Public Health Laboratory Service, London.

PMID- 7711542
TI  - The potential for marketing planning in an NHS trust.

PMID- 7711541
TI  - Elective ventilation of potential organ donors.
AB  - Elective ventilation describes the procedure of transferring selected patients
      dying from rapidly progressive intracranial haemorrhage from general medical
      wards to intensive care units for a brief period of ventilation before
      confirmation of brain stem death and harvesting of organs. This approach in
      Exeter has led to a rate of kidney retrieval and transplant higher than has been
      achieved elsewhere in the United Kingdom, with a stabilisation of numbers on
      patients on dialysis. Recently doubt has been cast on the legality of our
      practice of elective ventilation on the grounds that relatives are not permitted
      to consent to treatment of an incompetent person when that treatment is not in
      the patient's best interests. We are thus faced with the dilemma of a protocol
      that is ethical, practical, and operates for the greater good but which may be
      illegal. This article explores various objections to the protocol and calls for
      public, medical, and legal debate on the issues.

PMID- 7711543
TI  - Specialists in the United States: what lessons?

PMID- 7711544
TI  - ABC of rheumatology. Arthritis in children.

PMID- 7711545
TI  - Emergency care in general practice. Many general practitioners are unable to
      provide safe emergency care.

PMID- 7711546
TI  - Local research ethics committees and multicentre drug trials.

PMID- 7711547
TI  - Emergency care in general practice. Carrying heavy equipment may be impractical.

PMID- 7711548
TI  - Emergency care in general practice. General practitioners should be trained in
      cardiopulmonary resuscitation.

PMID- 7711549
TI  - Emergency care in general practice. Irish general practitioners learn immediate
      cardiac care.

PMID- 7711550
TI  - Emergency care in general practice. Should be properly recognised.

PMID- 7711551
TI  - Antibiotics carried in general practitioners' emergency bags. Having a central
      supplier would increase carriage of drugs.

PMID- 7711552
TI  - Antibiotics carried in general practitioners' emergency bags. May not be used
      when required.

PMID- 7711553
TI  - Follow up by telephone. Genitourinary medicine clinic gives results by telephone.

PMID- 7711554
TI  - Follow up by telephone. Phone clinic provides excellent support.

PMID- 7711555
TI  - Liver biopsy. Interventional radiology teams can provide prompt analgesia and
      care monitoring.

PMID- 7711556
TI  - Side effect of quinine for nocturnal cramps.

PMID- 7711557
TI  - Liver biopsy. Require imaging guidance.

PMID- 7711558
TI  - Liver biopsy. Day case procedure is safe.

PMID- 7711559
TI  - Liver biopsy. Most are performed by radiologists.

PMID- 7711560
TI  - Word of warning to junior ophthalmologists.

PMID- 7711561
TI  - Assessing blood glucose control in diabetes mellitus. Use precise analytical
      methods.

PMID- 7711562
TI  - Assessing blood glucose control in diabetes mellitus. Like should be compared
      with like.

PMID- 7711563
TI  - De inertia urbanorum. First law of thermodynamics applies.

PMID- 7711564
TI  - Identifying relevant studies for systematic reviews.

PMID- 7711565
TI  - Stress among doctors.

PMID- 7711566
TI  - What happened to care?

PMID- 7711567
TI  - Magnesium in acute myocardial infarction.

PMID- 7711568
TI  - Misleading meta-analysis.

PMID- 7711569
TI  - Abduction of infants from hospital.

PMID- 7711570
TI  - Accrediting hospitals.

PMID- 7711572
TI  - Babies' deaths linked to suboptimal care.

PMID- 7711571
TI  - Mutual trust?

PMID- 7711573
TI  - European Union tackles the greenhouse effect.

PMID- 7711574
TI  - Survey reveals men's ignorance about health.

PMID- 7711575
TI  - Performance bill will give GMC new powers.

PMID- 7711576
TI  - Australia attacks its immunisation rate.

PMID- 7711577
TI  - Criminal verdict outrages doctors in US.

PMID- 7711578
TI  - China considers voluntary euthanasia.

PMID- 7711579
TI  - Childhood leukaemia and non-Hodgkin's lymphoma near large rural construction
      sites, with a comparison with Sellafield nuclear site.
AB  - OBJECTIVE: To determine whether population mixing produced by large, non-nuclear
      construction projects in rural areas is associated with an increase in childhood
      leukaemia and non-Hodgkin's lymphoma. DESIGN: A study of the incidence of
      leukaemia and non-Hodgkin's lymphoma among children living near large
      construction projects in Britain since 1945, situated more than 20 km from a
      population centre, involving a workforce of more than 1000, and built over three
      or more calendar years. For periods before 1962 mortality was studied. SETTING:
      Areas within 10 km of relevant sites, and the highland counties of Scotland with
      many hydroelectric schemes. SUBJECTS: Children aged under 15. RESULTS: A 37%
      excess of leukaemia and non-Hodgkin's lymphoma at 0-14 years of age was recorded
      during construction and the following calendar year. The excesses were greater at
      times when construction workers and operating staff overlapped (72%),
      particularly in areas of relatively high social class. For several sites the
      excesses were similar to or greater than that near the nuclear site of Sellafield
      (67%), which is distinctive in its large workforce with many construction
      workers. Seascale, near Sellafield, with a ninefold increase had an unusually
      high proportion of residents in social class I. The only study parish of
      comparable social class also showed a significant excess, with a confidence
      interval that included the Seascale excess. CONCLUSION: The findings support the
      infection hypothesis and reinforce the view that the excess of childhood
      leukaemia and non-Hodgkin's lymphoma near Sellafield has a similar explanation.

PMID- 7711580
TI  - Weight growth in infants born to mothers who smoked during pregnancy.
AB  - OBJECTIVE: To determine whether maternal smoking during pregnancy causes
      impairment in growth after birth. DESIGN: Longitudinal study. SETTING: Six
      medical university centres of six towns of north, central, and south Italy.
      SUBJECTS: 12,987 babies (10,238 born from non-smoking mothers, 2276 from mothers
      smoking one to nine cigarettes a day, and 473 from mothers smoking > or = 10
      cigarettes a day) entered the study. MAIN OUTCOME MEASURES: Difference in weight
      gain between children born to smoking mothers and those born to non-smoking
      mothers. Weight was measured at birth and at 3 and 6 months of age. Maternal
      smoking habit was derived from interview on third or fourth day after delivery.
      RESULTS: Compared with children born to mothers who did not smoke during
      pregnancy, the birth weights of children born to mothers who smoked up to nine
      cigarettes a day were 88 g (girls) and 107 g (boys) lower; in children born to
      mothers who smoked > or = 10 cigarettes a day weights were 168 g and 247 g lower.
      At six months of age for the first group the mean weight for girls was 9 g (95%
      confidence interval -47 g to 65 g) higher and for boys 64 g (-118 g to -10 g)
      lower than that of children born to mothers who did not smoke. The corresponding
      figures for the second group were 28 g (-141 g to 85 g) lower for girls and 24 g
      (-136 g to 88 g) lower for boys. CONCLUSIONS: The deficits of weight at birth in
      children born to mothers who smoked during pregnancy are overcome by 6 months of
      age. These deficits are probably not permanent when smoking habit during
      pregnancy is not associated with other unfavourable variables (such as lower
      socioeconomic class).

PMID- 7711582
TI  - Surgical bleeding: unexpected effect of a calcium antagonist.

PMID- 7711581
TI  - Pressor reactions to psychological stress and prediction of future blood
      pressure: data from the Whitehall II Study.
AB  - OBJECTIVE: To examine whether reactions of blood pressure to psychological stress
      predict future blood pressure. DESIGN: Blood pressure was recorded at a medical
      screening examination after which pressor reactions to a psychological stress
      task were determined. Follow up measurement of blood pressure was undertaken, on
      average, 4.9 years later. SETTING: 20 civil service departments in London.
      SUBJECTS: 1003 male civil servants aged between 35 and 55 years at entry to the
      study. MAIN OUTCOME MEASURE: Blood pressure at follow up screening. RESULTS:
      Reactions of systolic blood pressure to stress correlated positively with
      systolic blood pressure at follow up screening (r = 0.22, P < 0.01). The dominant
      correlate of follow up blood pressure was blood pressure at initial screening (r
      = 0.60; P < 0.01 between initial and follow up systolic blood pressure; r = 0.59,
      P < 0.01 between initial and follow up diastolic blood pressure). Stepwise
      multiple regression analysis indicated that reactions to the stressor provided
      minimal prediction of follow up blood pressure over and above that afforded by
      blood pressure at initial screening. In the case of follow up systolic blood
      pressure, systolic reactions to stress accounted for only 1% of follow up
      variance; systolic blood pressure at initial screening accounted for 34%. With
      regard to diastolic blood pressure at follow up, the independent contribution
      from diastolic reactions to stress was less than 1%. CONCLUSION: Pressor
      reactions to psychological stress provide minimal independent prediction of blood
      pressure at follow up. Measurement of reactivity is not a useful clinical index
      of the course of future blood pressure.

PMID- 7711583
TI  - Prescription of regular aspirin in patients with chest pain referred to a
      cardiology outpatient clinic.

PMID- 7711584
TI  - Establishing a minor illness nurse in a busy general practice.
AB  - OBJECTIVE: To study the feasibility of a practice nurse caring for patients with
      minor illnesses. DESIGN: Nurse given training in dealing with patients with minor
      illnesses. Patients requesting a same day appointment were offered a nurse
      consultation. SETTING: Group practice in Stockton on Tees. MAIN OUTCOME MEASURES:
      Number of consultations which required a doctor contact, treatment, and rate of
      reconsultation. RESULTS: Of 696 consultations in six months, 602 (86%) required
      no doctor contact. 549 (79%) patients did not reconsult about the episode of
      illness, and 343 (50%) patients were given advice on self care only. CONCLUSION:
      Trained nurses could diagnose and treat a large proportion of patients currently
      consulting general practitioners about minor illness provided that the nurse has
      immediate access to a doctor.

PMID- 7711586
TI  - Time for change in traditional working practices?
AB  - Consultants in Britain are under pressure to change the way they organise their
      work. Many rely on formal, but unwritten, rules and a culture of "learning by
      doing." Unlike their counterparts in Sweden, they are often not well integrated
      into the management systems of their hospitals. The result is wide differences in
      the NHS workloads of individual consultants and, for a minority, conflicts of
      interest with their private work. The training received by junior doctors varies
      because it is largely left to individual consultants. Clinical directorates
      should provide a more effective mechanism for consultants to influence trust
      policies and for consultants to implement these policies. Consultants must not
      only recognise the need for change but also seize the initiative.

PMID- 7711585
TI  - Health service accreditation: report of a pilot programme for community
      hospitals.
AB  - Voluntary accreditation in the United Kingdom is being used by health care
      providers to improve and market their services and by commissioners to define and
      monitor service contracts. In a three year pilot scheme in the south west of
      England, 43 out of 57 eligible community hospitals volunteered to be surveyed; 37
      of them were ultimately accredited for up to two years by the hospital
      accreditation programme. The main causes for non-accreditation related to safety,
      clinical records, and medical organisation. Follow up visits in 10 hospitals
      showed that, overall, 69% of recommendations were implemented. An independent
      survey of participating hospitals showed the perceived benefits to include team
      building, review of operational policies, improvement of data systems, and the
      generation of local prestige. Purchasers are increasingly influenced by
      accreditation status but are mostly unwilling to finance the process directly.
      None the less, the concept may become an important factor moderating the quality
      of service in the new NHS.

PMID- 7711587
TI  - Decision analysis for medical managers.

PMID- 7711588
TI  - ABC of rheumatology. Raynaud's phenomenon, scleroderma, and overlap syndromes.

PMID- 7711589
TI  - Childhood thyroid cancer since accident at Chernobyl.

PMID- 7711590
TI  - Treatment of dysfunctional uterine bleeding. Serious complications may occur
      after hysteroscopic procedures.

PMID- 7711591
TI  - Treatment of dysfunctional uterine bleeding. Amenorrhoea need not be an end
      point.

PMID- 7711592
TI  - Treatment of dysfunctional uterine bleeding. Do women overreport nocturia?

PMID- 7711593
TI  - Treatment of dysfunctional uterine bleeding. Ignoring urinary incontinence may
      reduce long term satisfaction.

PMID- 7711594
TI  - Treatment of dysfunctional uterine bleeding. Appropriate comparison would be to
      compare the best of the old treatments with the best of the new.

PMID- 7711595
TI  - Treatment of dysfunctional uterine bleeding. Establish severity of blood loss and
      psychological status before surgery.

PMID- 7711596
TI  - Treatment of dysfunctional uterine bleeding. Vaginal hysterectomy is a certain
      cure.

PMID- 7711597
TI  - Treatment of dysfunctional uterine bleeding. Follow up survey in Taunton shows
      high level of satisfaction.

PMID- 7711598
TI  - Clonality in Langerhan's cell histiocytosis.

PMID- 7711599
TI  - Nutrition and lung health.

PMID- 7711600
TI  - Care in a midwife managed delivery unit. May not be the best option.

PMID- 7711601
TI  - Care in a midwife managed delivery unit. Analysis is invalid.

PMID- 7711602
TI  - Care in a midwife managed delivery unit. Conclusions are not supported by
      results.

PMID- 7711603
TI  - Care in a midwife managed delivery unit. Study shows interventionist nature of
      British obstetrics.

PMID- 7711604
TI  - Care in a midwife managed delivery unit. Medical staff did have input to unit.

PMID- 7711605
TI  - Failing sick doctors.

PMID- 7711606
TI  - Socioeconomic differences in mortality.

PMID- 7711607
TI  - Innovations in services and the appliance of science.

PMID- 7711608
TI  - Endoscopy in general practice.

PMID- 7711609
TI  - Non-steroidal anti-inflammatory drugs and elderly patients.

PMID- 7711610
TI  - Queues for cure?

PMID- 7711612
TI  - Russia hit by infectious diseases.

PMID- 7711611
TI  - Fish oils and cardiovascular disease.

PMID- 7711613
TI  - Children thrive without their greens.

PMID- 7711614
TI  - Chickenpox vaccine gets approval in US.

PMID- 7711616
TI  - Report paints picture of global use of cocaine.

PMID- 7711615
TI  - Ombudsman will rule on clinical complaints.

PMID- 7711617
TI  - Ombudsman in a white coat.

PMID- 7711618
TI  - Prophylactic aspirin and risk of peptic ulcer bleeding.
AB  - OBJECTIVE: To determine the risks of hospitalisation for bleeding peptic ulcer
      with the current prophylactic aspirin regimens of 300 mg daily or less. DESIGN: A
      case-control study with hospital and community controls. SETTING: Hospitals in
      Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth. SUBJECTS: 1121 patients
      with gastric or duodenal ulcer bleeding matched with hospital and community
      controls. RESULTS: 144 (12.8%) cases had been regular users of aspirin (taken at
      least five days a week for at least the previous month) compared with 101 (9.0%)
      hospital and 77 (7.8%) community controls. Odds ratios were raised for all doses
      of aspirin taken, whether compared with hospital or community controls (compared
      with combined controls: 75 mg, 2.3 (95% confidence interval 1.2 to 4.4); 150 mg,
      3.2 (1.7 to 6.5); 300 mg, 3.9 (2.5 to 6.3)). Results were not explained by
      confounding influences of age, sex, prior ulcer history or dyspepsia, or
      concurrent non-aspirin non-steroidal anti-inflammatory drug use. Risks seemed
      particularly high in patients who took non-aspirin non-steroidal anti
      inflammatory drugs concurrently. CONCLUSION: No conventionally used prophylactic
      aspirin regimen seems free of the risk of peptic ulcer complications.

PMID- 7711620
TI  - Respiratory tract infections and concomitant pericoronitis of the wisdom teeth.
AB  - OBJECTIVE: To discover if there is an association between respiratory tract
      infections and pericoronitis of erupting third molars in young adults. DESIGN:
      Data from male military conscripts' medical records were collected over five
      years and the incidence of respiratory tract infection before and after acute
      pericoronitis (191 cases) and before and after standard (722 cases) and operative
      (741) extractions compared with that in controls (n = 703) who had no infections
      in the third molar regions. SUBJECTS: 14,500 male military conscripts aged 20.
      SETTING: Garrisons in Valkeala and Kouvola, Finland. RESULTS: The incidence of
      respiratory tract infection was significantly higher during the two weeks before
      acute pericoronitis was diagnosed compared with that in controls. The highest
      incidence was observed in the three days before pericoronitis (odds ratio 6.8;
      95% confidence interval 3.0 to 15.0). The incidence was also increased in the
      first week after pericoronitis (odds ratio 3.7; 1.6 to 8.4) and three days before
      (odds ratio 2.6; 0.9 to 7.5) and during the first week after extraction of third
      molars (odds ratio 2.6; 1.3 to 5.3). CONCLUSIONS: Respiratory tract infection may
      precipitate and occur concomitantly with acute pericoronitis. Third molar surgery
      for pericoronitis, on the other hand, may trigger respiratory tract infection.

PMID- 7711619
TI  - Case-control study of migraine and risk of ischaemic stroke in young women.
AB  - OBJECTIVE: To determine whether migraine is a risk factor for ischaemic stroke in
      young women. DESIGN: A case-control study. SETTING: Five hospitals in Paris and
      suburbs. SUBJECTS: 72 women aged under 45 with ischaemic stroke and 173 controls
      randomly selected from women hospitalised in the same centres. MAIN OUTCOME
      MEASURES: Ischaemic stroke confirmed by cerebral computerised tomography or
      magnetic resonance imaging; history of headache recorded with structured
      interview, and diagnosis of migraine assessed by reproducibility study. RESULTS:
      Ischaemic stroke was strongly associated with migraine, both migraine without
      aura (odds ratio 3.0 (95% confidence interval 1.5 to 5.8)) and migraine with aura
      (odds ratio 6.2 (2.1 to 18.0)). The risk of ischaemic stroke was substantially
      increased for migrainous women who were using oral contraceptives (odds ratio
      13.9) or who were heavy smokers (> or = 20 cigarettes/day) (odds ratio 10.2).
      CONCLUSIONS: These results indicate an independent association between migraine
      and the risk of ischaemic stroke in young women. Although the absolute risk of
      ischaemic stroke in young women with migraine is low, the reduction of known risk
      factors for stroke, in particular smoking and use of oral contraceptives, should
      be considered in this group.

PMID- 7711621
TI  - Breast feeding and acute appendicitis.

PMID- 7711622
TI  - Labour and birth in water in England and Wales.

PMID- 7711623
TI  - Controlled trial of an audit facilitator in diagnosis and treatment of childhood
      asthma in general practice.
AB  - OBJECTIVE: To test whether an audit facilitator could alter the pattern of
      diagnosis and treatment of childhood asthma. DESIGN: Randomised stratified
      controlled trial. SETTING: 12 general practices in Tayside. SUBJECTS: 3373
      children aged 1-15 inclusive who had symptoms suggestive of asthma or possible
      asthma drawn from a systematic review of 10,725 general practice case records.
      INTERVENTION: Children were targeted for a clinical review by their general
      practitioner or practice nurses. MAIN OUTCOME MEASURES: Asthma related
      consultations, prescriptions, hospital attendances, and health service costs 12
      months before and after study. RESULTS: Compared with controls (n = 1563) the
      intervention group (n = 1585) had more practice initiated consultations for
      asthma (relative risk 2.18 (95% confidence interval 1.74 to 2.73)), new diagnoses
      of asthma (2.83 (2.26 to 3.54)), and past diagnoses reaffirmed (1.30 (1.08 to
      1.58)), and they were more frequently prescribed inhaled cromoglycate (1.52 (1.02
      to 2.25)). Hospital inpatient day rates fell from 152 to 122 in the intervention
      group and rose from 69 to 117 in the control group between the year before and
      the year after study. Total primary care costs rose from 30,118 pounds to 37,243
      pounds in the intervention group and fell from 29,131 pounds to 27,990 pounds in
      the control group. Hospital care cost fell in the intervention group from 25,406
      pounds to 20,727 pounds and rose in the control group from 12,699 pounds to
      19,650 pounds. CONCLUSION: An audit facilitator can favourably influence the
      pattern of diagnosis and treatment of childhood asthma in general practice. This
      may have an impact on health service costs.

PMID- 7711625
TI  - Using information for managing clinical services effectively.

PMID- 7711624
TI  - Management of atopic eczema. Joint Workshop of the British Association of
      Dermatologists and the Research Unit of the Royal College of Physicians of
      London.

PMID- 7711626
TI  - Where medical science and human behaviour meet.
AB  - Although we may be wrong about the details, we should try to imagine what the
      future holds for hospital consultants. The days of the independent consultant in
      the same post for 30 years are over, and there will be a change from "the"
      consultant to a few tiers of senior staff. Patients will increasingly demand to
      see specialists, so more specialists will be needed. As patients and their
      advocates become better informed the traditional rationing of clinical care to
      patients in Britain, such as restricting access to specialists, cannot continue.
      There is a current trend for evidence based health care, but the idea that each
      element of medical practice can be dictated by systematic evidence based research
      will prove to be naive--such research informs practice rather than dictates it.
      Science will continue to act as the guide to medical practice but specialists
      will not be turned into a set of logical operators running programs designed by
      health planners.

PMID- 7711628
TI  - ABC of rheumatology. Pain in the foot.

PMID- 7711627
TI  - Guidelines on appropriate indications for upper gastrointestinal endoscopy.
      Working Party of the Joint Committee of the Royal College of Physicians of
      London, Royal College of Surgeons of England, Royal College of Anaesthetists,
      Association of Surgeons, the British Society of Gastroenterology, and the
      Thoracic Society of Great Britain.
AB  - Upper gastrointestinal endoscopy is a valuable diagnostic tool, but for an
      endoscopy service to be effective it is essential that it is not overloaded with
      inappropriately referred patients. A joint working party in Britain has
      considered the available literature on indications for endoscopy, assessed
      standard practice through a questionnaire, and audited randomly selected cases
      using an independent panel of experts and an American database system. They used
      these data to produce guidelines on the appropriate and inappropriate indications
      for referral for endoscopy, although they emphasise that under certain
      circumstances there may be reasons to deviate from the advice given. The need for
      endoscopy is most difficult to judge in patients with dyspepsia, and this aspect
      is discussed in detail. Early endoscopy will often prove more cost effective than
      delaying until the indications are clearer.

PMID- 7711629
TI  - Rising emergency admissions. Age, distance from a hospital, and level of
      deprivation are influential factors.

PMID- 7711630
TI  - Rising emergency admissions. GPs must take some responsibility.

PMID- 7711631
TI  - Rising emergency admissions. Patients have rising expectations.

PMID- 7711632
TI  - Rising emergency admissions. Bed crises are occurring almost daily in some
      hospitals.

PMID- 7711633
TI  - Rising emergency admissions. More resources are required to facilitate the
      discharge of acutely ill elderly people.

PMID- 7711634
TI  - Health promotion in general practice.

PMID- 7711635
TI  - Criteria for authorship. Acceptance of a paper should not depend on where the
      researchers work.

PMID- 7711636
TI  - Criteria for authorship. Statisticians should be co-authors.

PMID- 7711637
TI  - Perinatal and infant postmortem examination. Non-invasive investigations are also
      helpful if permission for a necropsy is refused.

PMID- 7711638
TI  - Perinatal and infant postmortem examination. Paediatricians' opinions are also
      important.

PMID- 7711639
TI  - Perinatal and infant postmortem examination. Postmortem examinations are the
      final audit.

PMID- 7711640
TI  - Perinatal and infant postmortem examination. Quality of examinations must
      improve.

PMID- 7711641
TI  - Perinatal and infant postmortem examination. Survey of women's reactions to
      perinatal necropsy.

PMID- 7711642
TI  - Oral submucous fibrosis.

PMID- 7711643
TI  - Parents in the recovery room.

PMID- 7711644
TI  - Sedation in fibreoptic bronchoscopy. Doses that produce amnesia should be given.

PMID- 7711645
TI  - Sedation in fibreoptic bronchoscopy. Further study is needed.

PMID- 7711646
TI  - Sedation in fibreoptic bronchoscopy. Intravenous sedation is inappropriate in
      most minor procedures.

PMID- 7711647
TI  - Sedation in fibreoptic bronchoscopy. Patients must be monitored.

PMID- 7711648
TI  - Immunisation against chickenpox. Good argument exists for universal vaccination.

PMID- 7711649
TI  - Sedation in fibreoptic bronchoscopy. No grounds for abandoning sedation.

PMID- 7711650
TI  - Spontaneous fractures in cerebral palsy.

PMID- 7711651
TI  - Bone marrow transplantation. Extent of transplantation in Britain is
      overrepresented.

PMID- 7711652
TI  - Bone marrow transplantation. Review articles must accurately reflect current
      practice.

PMID- 7711653
TI  - Bone marrow transplantation. Comparative data on quality of care and outcome are
      urgently needed.

PMID- 7711654
TI  - Acute dissection of the thoracic aorta. Esmolol is safer than and as effective as
      labetalol.

PMID- 7711655
TI  - Acute dissection of the thoracic aorta. Magnetic resonance imaging is useful.

PMID- 7711657
TI  - [The effect of dielectric permeability of culture media on the transport activity
      of Ca2+,Mg2+-ATPase, solubilized from smooth muscle cell membrane].

PMID- 7711656
TI  - [The drug "anfen" and the energy status of the liver].

PMID- 7711658
TI  - [The effect of stimulating the limbic cortex and response of the vago-solitary
      nucleus complex, caused by stimulation of the vagus nerve].

PMID- 7711659
TI  - [Design and reactivity of large arterial walls in monkeys after prolonged
      hyperbaria].

PMID- 7711660
TI  - [Anthropogenic press, vector pathomorphology, and abundance of the Lyme disease
      pathogen].

PMID- 7711661
TI  - [Removal of the midventral gland affects behavior and mass of the Campbell
      hamster (Phodopus campbelli Thomas, 1905) adrenal glands: indications of the
      presence of a functional connection of specific cutaneous glands with the
      neuroendocrine system].

PMID- 7711662
TI  - Autoimmune neutropenia after unrelated bone marrow transplantation.
AB  - A 26-year-old male with Ph+ chronic myeloid leukemia, recipient of an HLA
      compatible marrow from a matched unrelated donor, showed good platelet
      engraftment coupled with poor neutrophil recovery. On day +33 the presence of
      surface-bound anti-neutrophil antibodies was detected by immunofluorescence. At
      variance with previously reported cases, the WBC count improved without any
      specific treatment, and the test became negative on day +42.

PMID- 7711663
TI  - Late extramedullary relapse following bone marrow transplant for AML presenting
      as acute renal failure and leukemic ascites.
AB  - A 22-year-old woman with AML in remission for 3.5 years after BMT relapsed with
      extramedullary disease presenting as leukemic ascites and recurrent obstructive
      renal failure. The duration of remission post-transplant and the absence of bone
      marrow involvement may suggest an improved likelihood of response to further
      chemotherapy.

PMID- 7711664
TI  - Juvenile CML revisited.

PMID- 7711665
TI  - Accelerated and long-term hematopoietic engraftment in mice transplanted with ex
      vivo expanded bone marrow.
AB  - Using a murine experimental model, we investigated whether ex vivo expansion of
      BM grafts under IL-3/IL-6 stimulation accelerates the early hematopoietic
      recovery of recipients of BM transplants. To facilitate the ex vivo expansion of
      hematopoietic progenitors, BM was first enriched in proliferatively active
      hematopoietic stem cells by a single treatment with 5-fluorouracil (5FU) 4 days
      prior to the BM harvest. The results showed that the number of CFU-GM and CFU-S12
      progenitors in the graft was significantly increased (56-fold and 14-fold,
      respectively), as a result of a 3 day incubation in the presence of IL-3 and IL
      6. Daily analysis of animals transplanted with 5 x 10(4) BM cells, either freshly
      harvested or expanded for 3 days, showed that the expanded grafts consistently
      allowed a faster hematopoietic recovery of recipients. Differences between both
      groups of transplanted animals were most evident when the number of either
      femoral or splenic CFU-GMs were compared, with increases close to 70-fold at the
      fifth day of engraftment being observed. Similarly, mice transplanted with
      expanded grafts showed a hastened recovery in the cellularity of both organs that
      was most significant during the second week following transplantation, with
      maximal increases of 15 and 40-fold in the BM and spleen, respectively.
      Differences in peripheral leukocyte numbers between both groups of recipients
      were much less remarkable than those observed in the hematopoietic organs,
      although from the nadir period to the 11th day post-transplantation differences
      ranging from twofold to sixfold were apparent, consistent with a higher rate of
      mouse survival.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711666
TI  - Salivary immunoglobulins in recipients of bone marrow grafts. I. A longitudinal
      follow-up.
AB  - Patients receiving bone marrow transplantation (BMT) are prone to a variety of
      bacterial, viral and fungal infections in their oral cavity. We have therefore
      followed alterations in salivary Ig levels associated with BMT. Most of the
      patients were transplanted with allogeneic, MHC-matched BM after T cells were
      depleted by ex vivo treatment with an anti-lymphocytic monoclonal antibody
      (Campath-1) and autologous complement. Parotid saliva was collected at various
      time intervals before and after BMT, and IgM, IgG and IgA concentrations were
      determined by an enzyme linked immunosorbent assay (ELISA). A gradual fall in Ig
      levels was detected following patient's conditioning with a combination of chemo-
      and radiation therapy beginning 10 days prior to BMT. A rise in the titer of
      salivary Ig could be detected as early as 4 days post-BMT, which increased
      continuously and reached plateau levels within 2-3 weeks. However, about 3 weeks
      later the Ig titers decreased again and persisted at low levels for variable
      periods of time. A second increase in salivary Ig was detected approximately 2
      months post-BMT, which persisted for prolonged periods of time. These results
      suggest that Ig secreted by donor B-lymphocytes and plasma cells passively
      transferred with the BM can rapidly reconstitute the salivary IgM, IgG and IgA of
      the immunocompromised recipient. However, when these cells cease to produce Ig
      the patients are still immunoincompetent and therefore enter a second phase of
      salivary Ig deficiency which may render them highly susceptible to opportunistic
      oral infections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711667
TI  - Effect of graft-versus-host disease prophylaxis on relapse in patients
      transplanted for acute myeloid leukemia.
AB  - Between November 1978 and September 1988, 184 patients with acute myeloid
      leukemia in first remission received marrow transplants from HLA-identical
      siblings after conditioning with 120 mg/kg of cyclophosphamide and 12.0 Gy
      fractionated total body irradiation. Patients received either cyclosporine (CYA,
      n = 59), methotrexate (MTX, n = 82), or MTX + CYA (n = 43 as graft-versus-host
      disease (GVHD) prophylaxis. The probabilities of grades II-IV acute GVHD after
      CYA, MTX or MTX+CYA were 0.43, 0.48 and 0.28, respectively (p = 0.06). The
      probability of non-relapse mortality was 0.53, 0.50 and 0.42 at 4 years in
      patients treated with CYA, MTX, or MTX + CYA, respectively. The probability of
      relapse was 0.24 in patients receiving CYA, 0.24 in patients receiving MTX and
      0.44 in patients receiving MTX + CYA (p = 0.02). The probability of survival at 4
      years was 0.54 with CYA, 0.51 with MTX and 0.45 with MTX + CYA. A multivariate
      analysis of risk factors for relapse examined age, WBC at diagnosis, blast count
      at diagnosis, percentage of marrow blasts, FAB subtype, the number of remission
      induction courses to achieve a remission, maintenance therapy, consolidation
      therapy, marrow cell dose, donor-recipient sex, GVHD prophylaxis regimen and
      isolation and decontamination in laminar airflow rooms. GVHD prophylaxis with MTX
      + CYA was independently significantly associated with an increased risk of
      relapse (relative risk 2.25, p = 0.01). Acute GVHD was associated with increased
      non-relapse mortality (RR = 3.58, p < 0.0001). The administration of MTX + CYA
      did not adversely affect survival because patients receiving this regimen
      experienced less mortality from causes other than relapse when compared with
      patients receiving either CYA or MTX alone.

PMID- 7711668
TI  - Fatal pneumococcal infections following allogeneic bone marrow transplant.
AB  - Six cases of fatal pneumococcal sepsis are described, occurring in the post
      allograft setting, between 3 and 39 months after transplantation. Five of the six
      patients were suffering from chronic graft-versus-host disease and were receiving
      immunosuppressive therapy. Most were receiving prophylactic antibiotic therapy.
      This represents approximately 2% of the allograft population treated during the
      study period who survived for > 3 months after transplant. Pneumococcal sepsis is
      thus still a significant cause of death after allogeneic BMT and approaches to
      minimise its occurrence are discussed.

PMID- 7711669
TI  - Antifungal prophylaxis with low-dose fluconazole during bone marrow
      transplantation. The Bone Marrow Transplantation Team.
AB  - The present study investigated the prophylactic efficacy of fluconazole at 100
      200 mg/day against invasive fungal infections during bone marrow transplantation
      (BMT). During July 1990 to December 1991, all BMT recipients received antifungal
      prophylaxis with fluconazole at either 200 mg/day or 100 mg/day. Historical
      controls were those that received no antifungal prophylaxis (January 1989 to June
      1990). Fungemia occurred in 4 of 112 fluconazole recipients and 8 of 79 controls
      (p < 0.05) prior to engraftment. Torulopsis (Candida) glabrata (three patients),
      Cryptococcus terreus and Candida tropicalis (mixed in one patient) caused
      fungemia in four patients in the fluconazole group; Candida albicans caused six
      of eight fungemic episodes in the controls. All three Torulopsis glabrata
      isolates were fluconazole-resistant. Colonization due to C. albicans was markedly
      diminished in the fluconazole group (19 of 112 patients versus 53 of 79
      controls). T. glabrata, on the other hand, was a more common colonizing organism
      in the fluconazole group (36 of 112 vs 10 of 79). The frequency of isolating C.
      albicans and/or T. glabrata was significantly different between fluconazole and
      control groups (p < 0.0001). Empiric use of amphotericin B therapy was markedly
      reduced in the fluconazole group (4.5% vs 34%; p < 0.0001). Fluconazole at 200
      mg/day or 100 mg/day appeared equally effective. Fluconazole at a daily dose of
      100 mg or 200 mg as antifungal prophylaxis during BMT: (1) significantly reduced
      the frequency of systemic fungal infections, (2) markedly reduced colonization
      and infection due to C. albicans, and (3) markedly reduced the need for empiric
      amphotericin B therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711670
TI  - Salivary immunoglobulins in recipients of bone marrow grafts. II. Transient
      secretion of donor-derived salivary IgA following transplantation of T cell
      depleted bone marrow.
AB  - Patients undergoing bone marrow transplantation (BMT) have decreased levels of
      salivary Ig over long periods of time. However, shortly after transplantation, a
      transient rise of Ig concentration in their saliva gland is detected. In order to
      trace the origin of this Ig, seven BM donors were immunized with tetanus toxoid
      (TT) 4-7 days prior to BMT harvesting. Four patients received BM from non
      immunized donors. All but one of the patients had no detectable anti-TT IgA in
      their parotid saliva prior to BMT. Recipients of T cell-depleted BM from pre
      immunized donors transiently displayed high titers of salivary anti-TT IgA 7-28
      days after transplantation. No significant anti-TT IgA titers were detected in
      saliva of patients grafted with non-immunized BM. We conclude that antibody
      producing cells activated in the donor are passively transferred with the BM to
      the recipient. IgA committed cells home to the mucosa-associated lymphoid tissues
      (MALT) and continue to secrete antibodies until senescence.

PMID- 7711671
TI  - Thalidomide in the management of chronic graft-versus-host disease in children
      following bone marrow transplantation.
AB  - Chronic graft-versus-host disease (GVHD) is the major complication in patients
      surviving > 100 days post-allogeneic bone marrow transplantation and occurs in
      30% of pediatric patients. It is most prevalent 1-2 years post-transplant.
      Treatment involves corticosteroids and other immunosuppressive therapy which may
      affect growth and increase the likelihood of infectious complications. We report
      five children with severe corticosteroid-dependent chronic GVHD treated with
      thalidomide 12-25 mg/kg/day. Response to therapy was based on resolution of
      symptoms of chronic GVHD and withdrawal of other immunosuppressive therapy. All
      the children showed clinical response to thalidomide with cessation or diminution
      in other immunosuppressive medication. Side-effects were minimal and no patient
      developed peripheral neuropathy. All patients are alive 48-65 months post
      transplantation. Thalidomide is a safe and effective drug for the treatment of
      chronic GVHD in children and may avoid the use of long-term corticosteroid
      therapy.

PMID- 7711672
TI  - Leukocyte-reduced transfusions of ABO-identical platelets and clinical outcome in
      autologous bone marrow transplantation for lymphoma.
AB  - In observational studies, use of ABO-identical platelets and leukocyte-reduced
      blood components have been associated with prolonged survival and reduced
      morbidity in acute leukemia. We present an analysis of the clinical results of
      instituting a policy of ABO-identical, leukoreduced transfusions in adult
      patients with lymphoma undergoing autologous bone marrow transplantation.
      Consecutive patients with Hodgkin's disease or non-Hodgkin's lymphoma were
      treated with a BEAC conditioning regimen. The use of ABO-identical platelets and
      leukoreduction of blood components was associated with reductions in mean number
      of days with fever > or = 38.5 degrees C (17 vs 10), number of days of
      antibiotics (34 vs 22) and numbers of days until recovery of neutrophil count >
      or = 500 x 10(6)/l (26 vs 18). Use of leukoreduced transfusions was the only
      statistically significant treatment factor predicting more rapid neutrophil
      engraftment. No significant difference in event-free or overall survival was
      observed. The differences in morbidity were not explained by variations in
      supportive care such as use of hematopoietic growth factors, use of peripheral
      blood stem cells or by any measures of pretransplant disease extent or severity.
      While conclusions based on cohort studies must be viewed conservatively, these
      data are consonant with observations from previous animal models and clinical
      studies. ABO-identical platelet transfusions and leuko-reduction are associated
      with reduced morbidity in patients undergoing autologous bone marrow
      transplantation for lymphoma.

PMID- 7711673
TI  - Subclinical disturbances in cardiac function at rest and in gas exchange during
      exercise are common findings after autologous bone marrow transplantation.
AB  - A study was undertaken to examine the effects of autologous bone marrow
      transplantation (BMT) on cardiac function at rest (n = 111) and pulmonary gas
      exchange during exercise (n = 110). Left ventricular cardiac ejection fraction
      (LVEF) was measured by radionuclide ventriculography before autologous BMT and
      after 6 months and 1, 3 and 5 years. Expired gas volume per oxygen consumption
      (VE/VO2) and transcutaneous PO2 were measured at rest and during submaximal
      exercise before and 6 and 12 months after autologous BMT, and the alveolar
      arterial oxygen difference was calculated after 12 months. In lymphoma patients
      conditioned with BCNU, cyclophosphamide, etoposide and cytarabine, a long-lasting
      reduction in LVEF of 11 +/- 14% mean (+/- SD) was noted. The risk of cardiac
      deterioration was not increased by a subnormal LVEF before autologous BMT or
      total body irradiation (TBI). Impaired gas exchange during exercise was a common
      feature, but severe disturbances were uncommon. During exercise transcutaneous
      PO2 fell pathologically in 15% and 20% of the patients examined after 6 and 12
      months, respectively, and the alveolar-arterial oxygen difference increased
      pathologically in 50% after 12 months. The VE/VO2 ratio increased significantly
      during exercise 6 months after autologous BMT in TBI-treated patients.

PMID- 7711674
TI  - Incidence of local CMV infection and acute intestinal GVHD in marrow transplant
      recipients with severe diarrhoea.
AB  - Intestinal biopsy samples derived from 22 consecutive patients with severe
      diarrhoea (> 1.5 1/day for 3 or more consecutive days) following allogeneic BMT
      were analysed for the local presence of cytomegalovirus (CMV) and histological
      and immunohistological alterations described as typical for acute graft-versus
      host disease (GVHD). Seventeen patients showed extensive histopathological
      lesions typical for acute intestinal GVHD grade > I, 14 marked GVHD-related
      immunohistological alterations. In intestinal biopsies from 10 of these 22
      patients CMV-DNA was detected using PCR- and in situ hybridisation techniques. In
      7 of these 10 CMV-DNA positive samples CMV protein expression and in 5
      cytomegalic cells were demonstrated. CMV could predominantly be shown in biopsies
      obtained from the ascending colon and/or the terminal ileum. All 10 patients with
      local CMV infection showed severe histopathological and immunohistological
      alterations described as typical for acute intestinal GVHD. Five of seven
      patients with a CMV-positive intestinal biopsy showed marked improvement of lower
      gastrointestinal tract disease on antiviral therapy. Five of seven patients
      lacking local presence of CMV but with severe histopathological lesions responded
      to therapy with high-dose steroids. Thus, PCR screening for CMV and
      histopathological analysis may help to treat lower intestinal disease in the
      marrow transplant recipient early and effectively.

PMID- 7711675
TI  - Interleukin-2 therapy after allogeneic bone marrow transplantation for acute
      myelocytic leukemia: studies in a relevant rat model for AML.
AB  - One of the major problems in the treatment of leukemia with BMT remains leukemia
      relapse. It has generally been established that allogeneic BMT, compared with
      autologous BMT, gives rise to a graft-versus-leukemia reaction (GVLR), usually
      associated with GVHD. To explore a possible role for post-BMT immunotherapy,
      recombinant human IL-2 therapy has been studied in the Brown Norway acute
      myelocytic leukemia (BNML), a rat leukemia model relevant for human AML. The
      antileukemic efficacy of rhIL-2 therapy is studied applying different doses of
      rhIL-2 after syngeneic or allogeneic BMT. rhIL-2 treatment post-syngeneic BMT
      showed a small, borderline significant GVLR. Repeated rhIL-2 treatment after
      allogeneic BMT resulted either in no significant antileukemic effect or in lethal
      GVHD when 'low' or 'high' doses were administered, respectively. An intermediate
      dose, however, induced a significant GVLR without the induction of (lethal) GVHD.
      Transplantation of allogeneic rat BM, which contains only a few lymphocytes, does
      not result in a significant GVLR or GVHD and thus resembles human HLA-matched
      allogeneic T cell-depleted (TCD) BMT. In conclusion, from the rat studies
      presented it appears that the GVLR lost by TCD of the allogeneic graft, may be
      more than fully compensated by IL-2 treatment post-allogeneic TCD BMT.

PMID- 7711676
TI  - Early deaths in children undergoing marrow ablative therapy and bone marrow
      transplantation.
AB  - We have reviewed the causes and risk factors for early death in a group of 295
      children who underwent any form of first bone marrow transplantation (BMT)
      between 1978 and 1992. The commonest indications for transplantation were acute
      lymphoblastic leukaemia 80 (27.1%), neuroblastoma 69 (23.3%), immune deficiency
      57 (19.3%) and myeloid leukaemias/myelodysplasia 50 (16.9%). There were 120
      (40.6%) allogeneic BMTs, 118 (40%) autologous BMTs, while 51 (17.2%) children
      usually with severe combine immune deficiency received BMT from a non-HLA
      identical parent, sibling or other relative (FBMT). Two were from identical twins
      and four from matched unrelated donors (MUD). Thirty-three children (11.2%) died
      in the first 100 days; the main causes of death being infection (n = 5), relapse
      (n = 7), graft failure (n = 4), GVHD (n = 7) and organ failure with or without
      infection (n = 6). There was no significant change in the incidence of early
      deaths in the three successive 5 year periods (1978-82, 1983-87, 1988-92)
      although there was some shift in the causes. Infections were the commonest cause
      during the first 5 year period, relapses followed by GVHD in the second period
      and single organ failure followed by GVHD and infections in the third period. The
      main causes of early death were relapse after high-dose chemo/radiotherapy and
      autologous BMT (7 of 9 deaths) and GVHD and infection after allogeneic BMT (9 of
      13 deaths). In the group of 51 children undergoing FBMT there were five deaths
      from infection, three from graft failure, one from organ failure and one from
      GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711677
TI  - High-dose therapy and autologous bone marrow transplantation for intermediate and
      high grade non-Hodgkin's lymphoma in patients aged 55 years and over: results
      from the European Group for Bone Marrow Transplantation. The EBMT Lymphoma
      Working Party.
AB  - The results of high-dose therapy and autologous BMT for patients with
      intermediate/high grade NHL were analysed in 82 patients aged > or = 55 years,
      identified from the EBMT lymphoma database. These were compared with the results
      for 82 patients aged < 55 years who were matched on the basis of disease status
      at transplantation, presence of bone marrow or CNS involvement and closest date
      of transplantation. The 5 year actuarial progression-free survival (PFS) for
      patients aged < 55 years was 33% compared with 37% for the > or = 55 year group
      (p = 0.08). Corresponding figures for overall survival (OS) were 39% and 38%,
      respectively (p = 0.19). No difference in outcome was observed according to
      histological subtype. Although the number of patients receiving total body
      irradiation (TBI) is small, a significantly lower PFS was observed in patients >
      or = 55 years receiving TBI-based high-dose regimens compared with younger
      patients. This difference was due to a higher toxic death rate in the older
      patient group. In this retrospective matched analysis, age > or = 55 years was
      not associated with lower PFS or OS following high-dose therapy and autologous
      BMT. The increased toxic death rate in patients receiving TBI suggests that this
      should be avoided in older patients, who should receive chemotherapy only high
      dose regimens.

PMID- 7711678
TI  - Neutropenic fever in patients after high-dose chemotherapy followed by autologous
      haematopoietic progenitor cell transplantation and human recombinant granulocyte
      macrophage colony stimulating factor.
AB  - Neutropenic fever has been one of the most difficult complications in the
      recovery period following high-dose chemotherapy and autologous haematopoietic
      progenitor cell transplantation. The differentiation between human recombinant GM
      CSF (sargramostim)-related fever and active infection can be difficult during
      this observation time. In 7 of 17 patients treated for metastatic breast cancer
      with HDCT and PBPC within 6 consecutive months, neutropenic fever without signs
      of infection was observed, which may be sargramostim-related fever. The typical
      presentation must fulfil the following criteria: cyclical elevation in body
      temperature that happens at the predicted time after sargramostim administration;
      absence of other signs or symptoms of infections; quick resolution of the fever
      after onset acetaminophen administration. Having met these criteria, none of
      these patients has been treated with intravenous antibiotics for active
      infections. At the time of haematological recovery (at a median time of 13 days
      from PBPC reinfusion to absolute neutrophil counts of > or = 0.5/nl) the febrile
      episode gradually resolved. No serious complications or other side-effects were
      observed. No toxic deaths occurred. Only if specific symptoms or signs of
      infection develop, would intravenous empiric antibiotic therapy be started.

PMID- 7711679
TI  - Hansenula anomala infection after bone marrow transplantation.
AB  - Hansenula anomala is a yeast which has seldom been reported as a human pathogen.
      A case of fungaemia with this organism is described in a 22-year-old patient with
      chronic myeloid leukaemia undergoing a second HLA-matched sibling transplant. A
      Hickman catheter was in situ and hyperalimentation commenced on day -1. Fever
      developed on day +10 and H. anomala was isolated from blood cultures. The patient
      was receiving cyclosporin and methotrexate as prophylaxis against graft-versus
      host disease and was severely neutropenic. Treatment with amphotericin B was
      commenced and the patient's Hickman catheter was removed. Fever resolved and
      subsequent blood cultures were negative. Amphotericin was continued to a
      cumulative dose of 680 mg and oral fluconazole 400 mg/day was given for a further
      week. H. anomala infection has been reported in premature babies and in
      immunosuppressed individuals but has not been previously observed in patients
      undergoing bone marrow transplantation. Clinical features of previously reported
      cases of infection with H. anomala are reviewed.

PMID- 7711680
TI  - Kaposi's sarcoma following allogeneic bone marrow transplantation.
AB  - Localised Kaposi's sarcoma (KS) was diagnosed 240 days after allogeneic bone
      marrow transplantation (BMT) in a severely immunosuppressed HIV negative patient
      with genetic predisposition. The tumour was of host origin, based on PCR
      amplification of DNA minisatellites. Treatment with radiotherapy prompted almost
      complete regression of the lesions. However the patient subsequently died with
      relapsed acute myelogenous leukaemia. Contrary to the incidence observed after
      organ allografts, the advent of KS appears to be exceptional after BMT, since
      only one case has been reported to date, following reinfusion of autologous
      marrow.

PMID- 7711681
TI  - Clinical Pharmacological Meeting. Groningen, The Netherlands, 7 October 1994.
      Abstracts.

PMID- 7711683
TI  - Meeting on Pharmaceutical Sciences, including Biopharmacy and Pharmaceutical
      Technology meeting. Leiden, The Netherlands, 2 December 1994. Abstracts.

PMID- 7711682
TI  - Pharmaceutical and Biomedical Analysis Meeting. Oss, The Netherlands, 18 November
      1994. Abstracts.

PMID- 7711684
TI  - Development of an improved target for [18F]F2 production.
AB  - An A1 body target with improved yields of electrophilic [18F]F2 on the
      Siemens/CTI 11 MeV proton cyclotron at Wisconsin has been developed. The
      saturation yield is 3.10 +/- 0.40 GBq/microA for beam currents up to 45 microA.
      The target has routinely produced 20-40 GBq of [18F]F2 for clinical and
      experimental use over 1600 microA-h operation, with a maximum yield to date of
      45.5 GBq (1.2 Ci). Target design, performance and reliability are discussed.

PMID- 7711686
TI  - Electronic quality of life questionnaires: a comparison of pen-based electronic
      questionnaires with conventional paper in a gastrointestinal study.
AB  - The use of pen-based electronic questionnaires and conventional paper
      questionnaires was compared in a randomized crossover study. Forty-six patients,
      aged 17-81 years, suffering from gastro-intestinal disorders, initially filled in
      a paper quality of life questionnaire for familiarization purposes, then on two
      subsequent visits completed electronic and paper questionnaires in randomized
      order. At the last visit they completed a preference survey. The results showed a
      high degree of acceptability of the electronic questionnaire, with 57% of patient
      preferring electronic and 13% preferring paper, while the remaining 30% expressed
      no preference. Neither age, gender nor familiarity with technology showed any
      marked association with patients' preferences. All patients found both paper and
      electronic questionnaires easy to use. Data were more complete on the electronic
      questionnaire (100%) than on the paper (99.1%). Data handling procedures were
      greatly simplified. These results show that major benefits in completeness of
      data, speed of data flow, and data handling workload can be obtained from the use
      of pen-based electronic questionnaires.

PMID- 7711685
TI  - Quality of life is not negatively affected by diet and exercise intervention in
      healthy men with cardiovascular risk factors.
AB  - Health-related quality of life was assessed in a diet and exercise intervention
      study among 157 healthy men aged 35-60 years (mean +/- s.d.; 46.2 +/- 5.0) with
      moderately raised cardiovascular risk factors. The men were randomized to four
      groups, diet (D, n = 40), exercise (E, n = 39), diet plus exercise (DE, n = 39),
      and no active intervention (controls (C) n = 39). Quality of life was measured
      with two self-administered questionnaires; Subjective Symptoms Assessment Profile
      and Minor Symptom Evaluation Profile, at baseline and after 1.5, 3 and 6 months.
      Cardiovascular risk factors were investigated at baseline and after 6 months. As
      a result of changes in dietary habits and physical exercise in the three
      intervention groups, several important cardiovascular risk factors were
      significantly reduced. The quality of life/well-being did not differ between the
      four groups and did not change significantly in any of the groups during the
      study. There was, however, a tendency towards fewer gastrointestinal symptoms in
      group D and fewer cardiac symptoms in group DE. We conclude that advice on
      lifestyle changes in the form of diet and exercise reduce risk factors in middle
      aged men without negative effects on their quality of life.

PMID- 7711687
TI  - Longitudinal sensitivity of generic and specific health measures in chronic
      sinusitis.
AB  - The utility of reliable health measures for longitudinal studies in chronic
      sinusitis depends on their ability to detect clinically relevant change. Sixty
      three patients with chronic sinusitis were evaluated before and three months
      after ethmoid sinus surgery using the Chronic Sinusitis Survey (CSS) and the
      generic Short-Form 36-Item Health Survey (SF-36). Statistically significant
      improvement was found for several SF-36 subscales including physical functioning,
      role functioning-physical, bodily pain, vitality and all CSS subscales. However,
      the differences between the instruments in longitudinal sensitivity to change as
      measured by standardized response means (SRM) and effect sizes (ES) were large.
      For the SF-36, sensitivity to change ranged from minimal to small (SRM: 0.01
      0.43; ES: 0.01-0.52) with bodily pain and role functioning-physical scores most
      sensitive. For the CSS, sensitivity to change ranged from moderate to large (SRM:
      0.56-0.82; ES: 0.48-1.12) with symptom-based and total index scores most
      sensitive. Despite this, the SF-36 yielded useful information concerning the
      relative burden of chronic sinusitis and failure of these patients to achieve
      normal levels of general health 3 months after sinus surgery. We conclude that
      the disease-specific CSS was more sensitive to change than the SF-36 survey in
      patients following ethmoid sinus surgery.

PMID- 7711688
TI  - Translation and validation of a quality of life instrument for Hispanic American
      cancer patients: methodological considerations.
AB  - The increasing diversity of the US population has drawn attention to the need for
      the development of quality of life tools that are appropriate for special
      populations, including Hispanic Americans, Asian Pacific Islanders, and Native
      Americans. The Hispanics are one of the fastest growing of these special
      populations, and this group includes persons who have lived in the USA for many
      generations, as well as recent immigrants. Both language and culture are
      important to consider when developing a quality of life tool for Hispanics. The
      initial aims of this study were to develop a Spanish translation of the CAncer
      Rehabilitation Evaluation System (CARES), perform content and construct
      validation of the Spanish CARES in Spanish-speaking and bilingual patients with
      cancer, and provide descriptive data on the rehabilitation needs and quality of
      life of these patients. However, in performing this study we encountered a number
      of methodological problems that had not been previously described in the
      literature, including the need for idiomatic translations, lack of familiarity
      with questionnaires, low acculturation and low literacy rates among Hispanic
      cancer patients in the southwestern USA. We suggest a number of practical
      considerations for future investigators planning to develop quality of life tools
      for this special population.

PMID- 7711689
TI  - Assessment of patients with menorrhagia: how valid is a structured clinical
      history as a measure of health status?
AB  - A patient-administered questionnaire for menorrhagia based on the type of
      questions asked when taking a gynaecological history was developed and tested
      using the following steps: literature reviews, devising the questions, testing
      responses for internal consistency and test-retest reliability and validating the
      questionnaire by comparing patient's scores with their responses to the SF-36
      general health measure, and with family practitioner perceptions of severity. The
      main sample consisted of 351 women with menorrhagia, 246 referred to gynaecology
      ambulatory clinics and 105 from four large training practices in North-east
      Scotland. Following testing, two questions were discarded from the questionnaire.
      The final questionnaire demonstrated a good level of reliability and the
      resulting patient scores correlated significantly with their scores on the scales
      making up the general health measure. The questions asked in taking a clinical
      history from a woman with menorrhagia can be used to construct a valid and
      reliable measure of health status. This clinical measure may be a useful guide in
      selection for treatment and in the assessment of patient outcome following
      treatment.

PMID- 7711690
TI  - Area under the curve: a metric for patient subjective responses in episodic
      diseases.
AB  - Herpes zoster manifests as a characteristic painful rash that resolves within 2
      months of initial presentation in 90% of patients. As pain is a hallmark of the
      disease, the severity of an episode can be described by the magnitude and
      duration of pain. The Brief Pain Inventory (BPI) was used to follow the daily and
      weekly amount of pain reported by 50 patients with herpes zoster. Results
      demonstrate that the BPI is a reproducible, responsive and valid measure of pain
      due to herpes zoster. From the individual responses on the BPI, the area under
      the curve (AUC) for each patient was derived from the pain reported on sequential
      administrations of the BPI. This metric was simple to calculate, easy to explain
      and captured two dimensions of this episodic disease (magnitude and duration of
      pain) in a single continuous measure. AUC could prove useful in the application
      of patient response data to intervention trials in diseases that are of an
      episodic nature.

PMID- 7711691
TI  - Sensitivity to change of health status measures in a randomized controlled trial:
      comparison of the COOP charts and the SF-36.
AB  - This study compared the sensitivity to change of comparable dimensions of a multi
      item multi-dimensional health status measure (the SF-36) with the equivalent
      single item domains on the Dartmouth COOP charts. One hundred and twenty nine
      patients were randomized to either day case laparoscopic surgery (n = 60) or open
      inguinal hernia repair (n = 69). Respondents completed the SF-36 and COOP charts
      at baseline (prior to surgery) and at follow up at 10 days and 6 weeks.
      Equivalent dimensions of physical functioning, mental health/emotional condition,
      social activities, pain and overall condition/general health on the two
      questionnaires were compared. Despite slightly different pictures of change
      provided by the physical functioning and 'overall condition/general health'
      dimensions the general picture of change provided by the two instruments was
      similar. At 10 days, patients who underwent open surgery reported far greater
      levels of dysfunction than those who underwent laparoscopic surgery on both
      questionnaires. At 6 weeks the pain dimension of both questionnaires indicated a
      large improvement from baseline, whilst no other domain on either questionnaire
      for either group indicated such improvement. The general picture of change
      provided by the two measures was similar. The results suggest that both the SF-36
      and the COOP charts may prove suitable for the assessment of health perception
      outcomes in surgical clinical trials. Differences on certain domains were caused
      in large measure by the nature of the questions posed. The study once again
      highlights the importance of checking item content to determine the suitability
      of any particular measure for a given study.

PMID- 7711693
TI  - The need for an intermediate cardiorespiratory unit.

PMID- 7711694
TI  - Effects of spontaneous FEV1 fluctuation on airway reversibility estimation.
AB  - Assessment of bronchodilator responsiveness is currently based on criteria
      derived from population studies, which provide information on the intrasubject
      variability of forced expiratory volume in one second (FEV1). These criteria
      themselves, however, differ from each other; and confusion exists on the best way
      of expressing reversibility. The aims of this study were to measure spontaneous
      FEV1 variability individually, and to see its impact on the response to
      salbutamol. Fifty patients with different types and degrees of chronic airflow
      obstruction were included in the study. FEV1 was measured twice, with an interval
      of 20 min, in order to assess spontaneous variability. Spirometry was repeated
      following salbutamol inhalation, and two estimates of reversibility were obtained
      using the two FEV1 measurements obtained at baseline. Strong correlations were
      found between the two estimates, and the mean of the differences between the two
      reversibility estimates was 65.40 +/- 65.68 ml, when expressed in absolute terms.
      FEV1 responses to salbutamol were superior to the spontaneous variation in FEV1
      in 48 (96%) of the patients. Linear regression analysis revealed that there was a
      highly significant correlation between the baseline FEV1 and the response to
      salbutamol (r = 0.50 and 0.43, for the first and the second estimates,
      respectively). These results suggest that the decision on reversibility should
      not be based on distinct cut-off levels, but rather should be assessed
      individually, as intrasubject variability seems to be almost always less than the
      patient's response to bronchodilators.

PMID- 7711695
TI  - Better medication compliance is associated with improved control of childhood
      asthma.
AB  - Our previous studies have shown that medication compliance in children prescribed
      continuous treatment for asthma is poor, and that an intervention can improve the
      level of compliance. The present study examined the effects of an intervention on
      the clinical course of moderately severe asthma. At each of six clinic visits,
      spirometry was performed, medication compliance was assessed by questionnaire,
      and the physicians made an overall assessment of asthma severity (Severity Score)
      and provided a score for asthma control (Control of Asthma Score). Peak
      expiratory flow rates were measured twice daily for one month prior to each
      clinic visit, and the coefficient of variation (% CV) was calculated. Subjects
      received the intervention after at least two visits, and 53 of the 78 recruits
      completed the study. Following the intervention, % CV, Control of Asthma Score,
      Severity Score and % compliance improved, showing that better medication
      compliance was associated with better control of moderately severe asthma.

PMID- 7711696
TI  - Primary mediastinal seminoma.
AB  - We describe three cases of primary mediastinal seminoma, a rare neoplasm
      histologically similar to the testicular form, which mainly affects men between
      30-60 yrs of age. Case No. 1--a 45 year old patient was treated with a
      combination of radiotherapy and chemotherapy. Twenty six months after the
      diagnosis, the patient shows a limited residual lesion, a good general health
      status and was asymptomatic. Case No. 2--a 56 year old patient was admitted for
      suspected epithelial lung cancer, with subsequent histological diagnosis of
      seminoma on surgical sample. The exeresis of the lesion was followed by
      radiotherapy and chemotherapy, the latter interrupted owing to the onset of
      thrombotic complications resulting in the patient's death. Case No. 3--a 35 year
      old patient was subjected to diagnostic and therapeutic thoracotomy, with
      diagnosis of primary mediastinal seminoma. The surgical therapy was followed by a
      cycle of radiotherapy. Five years later, the general health of the patient is
      good and he is still asymptomatic. In the discussion we consider the
      embryogenesis, clinical picture, radiological and anatomicopathological aspects,
      typical biomarkers of cancer, diagnostic procedures and therapeutic protocols
      currently followed.

PMID- 7711692
TI  - Quality of life bibliography and indexes: 1993 update.

PMID- 7711697
TI  - Proceedings of International Workshop on Cardiorespiratory Intermediate Intensive
      Care. Brescia, Italy, 21-22 April 1994.

PMID- 7711698
TI  - Cardiorespiratory intermediate intensive unit: heart-lung interactions.
AB  - The heart and lung (the body's gas transport system) are neurally, mechanically,
      humorally and functionally linked. Several clinical-therapeutic consequences
      involve heart-lung interactions. Three of these conditions are described here: 1)
      pulsus paradoxus in asthma; 2) survival in chronic cor pulmonale; and 3) Cheyne
      Stokes breathing in congestive heart failure. They provide examples of the
      pathophysiological and clinical complexity that such correlations involve. The
      most remarkable "effects" of the heart-lung relationship as a metabolic unit are
      represented by development of cardiorespiratory intensive care units, and efforts
      to bring about methods of monitoring cardiorespiratory function.

PMID- 7711699
TI  - Acute respiratory failure.
AB  - Respiratory failure is a severe impairment of pulmonary gas exchange, consequence
      of lung failure leading to hypoxaemia and/or pump failure causing hypercapnia.
      Acute respiratory failure (acute lung injury and asthma) or acute on chronic
      respiratory failure (COPD and chest wall disorders) are the two terms proposed to
      characterize different onset and development. Mechanical ventilation, is often a
      necessary life-saving treatment in many critically ill patients, it is associated
      with complications such as infection or barotrauma. Other innovative techniques
      are mask ventilation and proportional assist ventilation (PAV). The major aim of
      mask ventilation is to prevent complications related to tracheal intubation,
      particularly respiratory tract infections and barotrauma.

PMID- 7711700
TI  - Intermediate intensive units: definition, legislation and need in Italy.
AB  - This paper deals with the definition of intensive care medicine and the
      organization of different levels of care; intermediate and high level. The
      organization, facilities and personnel for intermediate care are discussed. The
      available public data on the organization of intensive medicine and modifications
      planned by the Legislator are considered. Finally, the usefulness of intermediate
      care and an estimate of the actual need, based on prospective multicentre ad hoc
      studies, are discussed.

PMID- 7711701
TI  - Location and architectural structure of IICU.
AB  - When an Intermediate Intensive Care Unit (IICU) is planned, three groups of
      professionals are usually involved: the managers of the hospital, the architects
      and the staff. Although several aspects and problems related with the building of
      IICUs are considered in the specialized literature, lack of communication and
      discussion of the appropriate issues at the appropriate time is the origin of
      several errors during the planning and building of IICUs. Standards of IICU for
      respiratory departments have been proposed by the Working Group "Rehabilitation
      and Intensive Care" of the Italian Hospital Pneumologist Society. An ideal IICU
      should include 4-6 beds for a hospital with more than 500 patients.
      Alternatively, an IICU should have 1-2 beds per 100,000 inhabitants. IICU should
      be located in the hospital, integrated with, but well distinguished from, the
      respiratory department, and with easy accessibility to surgery, Intensive Care
      Unit (ICU), laboratory, radiodiagnostics, cardiology, etc. No more than two beds
      should be included per room, and isolation should be necessary only for those
      patients suffering from communicable or infectious diseases, and also for those
      patients requiring protective isolation or suffering from disorientation or
      severe emotional disturbance. Limitation of single room usage is due also to
      economic considerations; isolation requiring 50-100% more personnel per bed than
      an open ward. Individual continuous monitoring should be allowed. Visits and
      nursing by relatives and/or care-givers should be encouraged, with appropriate
      space and facilities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711702
TI  - Intermediate respiratory care unit: admission criteria.
AB  - Intensive care unit (ICU) management of patients on partial ventilatory support
      is very costly. We opened an intermediate respiratory care unit (RCU), with the
      aim of providing cost beneficial in-hospital and home care for patients who
      require mechanical ventilation for at least 8 h.day-1. Prior to admission to an
      intermediate RCU, it is mandatory to take into consideration not only the
      patient's overall health status but also his or her prognosis, and rehabilitation
      chances and environmental factors have to be evaluated.

PMID- 7711703
TI  - Cardiological monitoring in a respiratory intermediate intensive care unit.
AB  - The appearance, in the last few years, of respiratory intermediate intensive care
      units (RIICU) has created a requirement of close collaboration among different
      physicians. The role of a cardiologist in a RIICU is well recognized as an
      important component to the pulmonolgist. The diagnostic tools for the
      cardiologist in a RIICU should be separated into two sections: in the first one
      specific and mandatory devices for monitoring are included; in the other second
      choice instruments and methods are considered. A 24h ECG monitoring system,
      noninvasive Pa recording, central venous pressure evaluation set from peripheral
      vein, pumps for infusive therapies and cardiac echo-Doppler have to be considered
      necessary. Specific ECG monitoring system and right heart catheterization or
      arterial cannulation cannot be mandatory for these patients. The presence of a
      cardiologist in a RIICU can facilitate adequate cardiac monitoring in respiratory
      patients.

PMID- 7711704
TI  - Respiratory monitoring in an intermediate intensive unit.
AB  - The major goal of monitoring is continuous recording of indices that enhance our
      understanding of the underlying pathophysiology, in order to improve diagnosis
      and guide management, and identify trends that assist in assessing the
      therapeutic response and predicting prognosis. Nowadays, technology has made it
      possible to automatically sense and display a wide variety of physiological
      indices. An ideal monitoring system should be pertinent to patient management,
      propose interpretable data, show high technical accuracy, high sensitivity, good
      reproducibility, be practical to use. The international literature, our personal
      experience, and cost considerations have proposed the following monitoring
      standards as the best for a noninvasive respiratory intermediate intensive care
      unit (RIICU): 1) mandatory indices: respiratory rate, oxygen saturation, haemogas
      analysis, tidal volume, minute ventilation, maximum voluntary ventilation, forced
      expiratory volume in one second, forced vital capacity, vital capacity, maximal
      inspiratory pressure, heart rate and blood pressure; 2) second choice indices:
      capnometry, respiratory inductive plethysmography, transcutaneous monitoring of
      gases, haemodynamic monitoring, mechanics data by means of an oesophageal
      balloon, and central drive. Pulmonary monitoring devices shorten the time for
      patients who remain on mechanical ventilators; a reduction both in the risk of
      associated complications and the costs involved is a natural consequence.
      Continuous monitoring of significant physiological indices has the potential for
      predicting a critical event, and providing an opportunity for the institution of
      lifesaving measures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711705
TI  - Ventilation techniques: invasive versus noninvasive.
AB  - Conventional medical treatment of COPD patients with acute respiratory failure
      (ARF) was associated with an overall mortality ranging 12-29%. When conservative
      treatment fails, ARF is usually managed by means of mechanical ventilation (MV)
      via an endotracheal tube (ET) or tracheostomy. Mortality of COPD patients with
      ARF treated with invasive MV ranged 21-54%. Invasive MV is associated with
      several complications. Positive pressure ventilation (PPV) by means of facial or
      nasal masks have been used in place of endotracheal intubation in ARF: the
      results are promising. Advantages of mask ventilation include the possibility of
      intermittent delivery of ventilation, use of different modalities of ventilation,
      the ability to undertake normal swallowing, feeding and speech, the possibility
      of physiological air warming and humidification, the possibility of coughing, and
      an easier weaning whilst still maintaining possibilities of ET intubation.
      Reported side-effects during mask PPV include mask discomfort, skin reddening,
      dry nose, air leaks, eye irritation and gastric distension. Mortality of COPD
      patients treated with noninvasive PPV ranged 6-25%. The level of severity of
      basal acidosis and blood gas response to a short trial of noninvasive PPV were
      predictive of success of this modality of MV. Preliminary results suggest that
      one year mortality after MV is reduced with noninvasive PPV in comparison to ET
      ventilation.

PMID- 7711706
TI  - External negative pressure ventilation techniques.
AB  - External ventilation was introduced at the beginning of the century to treat
      acute and chronic respiratory failure. Long-term negative pressure ventilation
      (NPV) has proved useful in patients with respiratory failure, secondary to a
      restrictive impairment of neuromusculoskeletal origin. Although NPV may be
      successfully used in acute-on-chronic respiratory failure in patients with
      chronic airflow obstruction (CAO), its use in the long-term management of this
      type of patient seems much less promising. The various types of ventilators, iron
      lung, pneumo-wrap and cuirass are discussed. All these prostheses, except for the
      pneumo-wrap, are connected to a pump able to generate negative and positive
      pressure. NPV must be a controlled ventilation, because an effective trigger is
      not yet available. The most important feature of the ventilator must be the
      ability to vary the ventilatory pattern to adapt the machine drive to the patient
      drive. The goal of NPV is not only to normalize gas exchange, but also to restore
      an effective spontaneous ventilation. This kind of ventilation has no negative
      effects on haemodynamics, because it does not vary physiological gradients of
      transthoracic pressure. However, due to lack of coordination between the
      respirator and the pharyngeal muscles of the patient, obstructive apnoeas may
      occur during NPV in sleeping patients.

PMID- 7711707
TI  - The unweanable patient.
AB  - Inspiratory muscles can be exerted to their maximal limits during situations of:
      1) high ventilatory demands, such as in exercise; and 2) during cases of high
      force demands, as in obstructive or restrictive diseases. In either circumstance,
      the level of sustainable activity (many hours) seems to be about half of the
      subject's maximal ventilatory capacity (MVC) or their maximal inspiratory
      pressure (MIP), respectively. The natural history of chronic hypercapnia in
      chronic obstructive pulmonary disease (COPD) or in neuromuscular disease suggests
      that spontaneous ventilation is set at a level below that which will trigger
      muscle fatigue, even if this lower level results in "chronic ventilatory
      failure". When this type of patient suffers a pathology that further decreases
      their global respiratory muscle function or increases their load, we have the
      makings of an unweanable patient; the mechanical ventilator ultimately replaces
      the lost inspiratory muscle function. Given time for the muscle to recover force
      and a reduction of the loads should, thus, be the therapeutic focus.

PMID- 7711708
TI  - Ventilatory techniques during weaning.
AB  - Ventilatory techniques are only a part of the weaning process, that also includes
      medical therapy, physiokinesitherapy, nutrition, psychological support and
      nursing. Traditional ventilatory techniques used in weaning are: T-piece trials
      (alternated with assist-control ventilation (ACV)), pressure support ventilation
      (PSV), intermittent mandatory ventilation (IMV) and continuous positive airway
      pressure (CPAP) ventilation. None of these techniques has been demonstrated to be
      better than the others, and the physician must be prepared--to try alternate
      strategies according to the kind of patient. Noninvasive mechanical ventilation
      (NIMV) can be successfully used in weaning from invasive mechanical ventilation.
      Furthermore, NIMV by nasal or facial mask has been successfully used in the
      treatment of acute respiratory failure (ARF) due to various pathologies. In these
      cases, the weaning trial has an immediate beginning, since noninvasive
      ventilation is performed alternatively with spontaneous breathing after the early
      phase of ARF.

PMID- 7711709
TI  - Weaning and outcome from mechanical ventilation.
AB  - Weaning means the ability of a patient to breath spontaneously after mechanical
      ventilation. In chronic obstructive pulmonary disease (COPD) patients, inability
      to tolerate discontinuation of mechanical ventilation is reported to have an
      incidence of 25-60%. It is, therefore, important to employ simple parameters able
      to predict weaning success, since, in the case of failure, the validation of
      predictive indices of weaning may also contribute to the decision of whether or
      not these patients should eventually enter a programme of home ventilation. Among
      other indices employed, respiratory frequency/tidal volume (f/VT) ratio,
      compliance, rate, oxygenation and pressure (CROP) index, mouth occlusion pressure
      (P0.1) and static compliance of the respiratory system have been shown to be
      quite accurate. The survival at one year of these patients requiring mechanical
      ventilation ranges 34-49%. Indeed, there is a particular subset of COPD patients
      in whom mechanical ventilation is prolonged due to the severity of their
      pathology. We studied 42 of these patients requiring mechanical ventilation for
      more than 21 days, to assess with simple parameters (arterial blood gases,
      pulmonary function tests, respiratory muscle force, P0.1, nutritional status)
      their potential for weaning and their survival at 2 yrs. Using discriminant
      analysis, and employing an equation comprising maximal inspiratory pressure (MIP)
      and arterial carbon dioxide tension (PaCO2), we were able to predict the patients
      able or unable to be weaned with an accuracy of almost 85%.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7711710
TI  - From intermediate intensive unit to home care.
AB  - The procedure of discharging the chronically ill respiratory patient from an
      intermediate intensive care unit (IICU) is always difficult and requires
      multidisciplinary intervention. A complete clinical and functional evaluation is
      necessary during the period of hospitalization to determine the weaning
      possibilities and the respiratory performance of the patient in care. In-hospital
      management should also be able to produce an accurate plan for home care,
      especially in those subjects for whom ventilatory support cannot be denied.
      Appropriate instruction for the care-givers involved must be provided. Funding
      requirements should be carefully evaluated. Four hundred and sixty five
      chronically, critically ill respiratory patients were admitted to our
      cardiopulmonary IICU (34% of the total patients admitted) coming from intensive
      care units (ICUs) or other departments. The death rate was 6%. Six patients were
      transferred to an ICU due to urgent necessity. Three hundred and thirty eight
      subjects were mechanically-ventilated (115 invasively), and 23 were finally
      admitted to a long-term home-care programme. Nowadays, the respiratory IICU can
      be considered a new hospital ward, where appropriate monitoring can be performed
      and accurate evaluation for discharge should be planned. Knowledge of worldwide
      experience is necessary to establish the best way to discharge patients from a
      respiratory IICU and to eventually recommend them for a home-care programme.

PMID- 7711711
TI  - From mechanical ventilation to home-care: the psychological approach.
AB  - The mechanically ventilated individual has to cope with being in a situation of
      total dependence on a bodily external object for life-support. This condition may
      give rise to unprecedented psychological complaints, often concerning the
      patient's fear of death, feeling of abandonment, mutilation, and perceived
      changes of self-image. It is not only the patients but also their family members
      who will need help dealing with stressful situations, false beliefs, anxiety, and
      all the other emotions linked to mechanical ventilation. After discharge from the
      hospital, the immediate need to master and manage the home ventilator equipment
      may overshadow the psychological needs of the patients. Therefore, psychological
      support should be offered well before discharge, and periodically during
      ambulatory sessions. Another important factor associated with adaptation to
      mechanical ventilation and the following period at home, appears to be the level
      of communication within the family, and the degree of commitment between all
      family members. Helping patients and their family members to cope with technical
      and psychological aspects of mechanical ventilation will make the transition from
      the hospital environment to the home easier for both. From an ethical point of
      view, it is suggested that patients be informed that ventilation will not change
      the course of their underlying disease or prognosis.

PMID- 7711712
TI  - Intermediate respiratory care unit: rehabilitation.
AB  - The ventilator assisted individual (VAI) represents a complex set of medical and
      social issues that call for the involvement of multiple interest groups. The
      success of treatment for VAI depends on many factors. These include: appropriate
      selection of patients for care outside the hospital, clinical and physiological
      stability of patients, patient and family motivation, and their ability to learn.
      Assisted ventilation in chronic respiratory failure secondary to chest-wall
      deformities and neuromuscular disease has shown promising results. Less
      satisfactory have been those reported in patients with chronic obstructive
      pulmonary disease (COPD). COPD candidates for chronic mechanical ventilation
      should be carefully selected. Patients should not be discharged on ventilators to
      nonhospital environments before they are clinically stable. It is also crucial to
      rule out other medical diseases that could interfere with successful discharge
      and home-care. Discharge planning requires the support and involvement of the
      physicians, nurses, and other allied health professionals. Education is of vital
      importance and, as such, needs to begin early in the patient's hospital stay. A
      basic checklist of skills that the VAI and the family will need to know should be
      developed, as well as an individual rehabilitation programme planned according to
      the patient's primary problem, with realistic short- and long-term goals. The aim
      is to restore and maintain the best possible quality of life for the individual.

PMID- 7711713
TI  - Professional figures in intermediate intensive units.
AB  - In Italy, respiratory intermediate intensive care units (IICUs) are not yet
      considered as autonomous hospital departments. The IICU of the Rehabilitation
      Department of the Medical Centre of Gussago (12 monitored beds) provides care for
      respiratory and cardiac patients. Ventilatory assistance and noninvasive
      modalities both in treatment and monitoring suggest a multidisciplinary approach
      to the patient. Highly professional figures should, therefore, be singled out to
      provide care in a respiratory IICU. The medical staff is composed of one
      anaesthesiologist, one cardiologist and one pulmonologist, who can integrate care
      when respiratory complications occur in a cardiological patient, or when cardiac
      events affect a respiratory patient. Nurses are capable of specific activities,
      especially when ventilatory assistance is required. The presence of a
      physiotherapist reduces the nursing workload, especially for ventilated
      individuals. The psychological aspect is undertaken by a specialist. Finally, an
      expert in nutrition provides an individualized dietary regimen. Our 4 year
      experience encourages such a multidisciplinary approach. An ideal integration of
      the professional activities should provide adequate and individual care for
      patients admitted to an IICU.

PMID- 7711714
TI  - Medical and legal problems in intermediate intensive units.
AB  - Due to a lack of legislation on the subject (the only data concerns the standard
      of hospital personnel in the Ministerial Decree (DM) of 13th September 1988), the
      medical and legal problems are concerned, in the first instance, with defining
      the type of unit, the context within which it can be placed and the eventual
      access to essential services and minimum equipment. With regard to
      responsibility, bearing in mind that the medical team of the intermediary unit
      (as with all other hospital teams) is employed by the public National Health
      Service, medical malpractice can be associated with lack of equipment and an
      inadequate public health service, which is often the cause. If penal
      responsibility is strictly personal (art. 27 of the Constitution) the civil
      relationship is, on the one hand, a relationship between the administration and
      the patient (the physician as employee must give his services within the Health
      Service and does not have an official personal relationship with the patient) so
      the Hospital organisation has a contractual type of civil responsibility whereas
      the employed doctors have an extra-contractual responsibility with different
      obligations. These responsibilities, which are also determined by the functions
      of the physician within the USL Health Service (DPR n. 761/1979), can also
      include control of non-medical staff, control of the equipment, specific training
      of personnel, etc. Problems concerning the admission of patients to the
      intermediate unit must also be taken into account (precise evaluation of the
      indications and of the type of patient to be admitted, refusal of patients in
      such a condition as to require intensive care or invasive techniques.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7711715
TI  - Iron lung treatment of acute on chronic respiratory failure: 16 yrs of
      experience.
AB  - Noninvasive ventilatory supports are gaining a prominent position among
      ventilatory techniques aimed to improve ventilation in patients with acute-on
      chronic respiratory failure (ACRF). It has not yet been established whether these
      techniques can be considered as a preventive measure to avoid the need for
      endotracheal intubation, or are really another means to provide full ventilatory
      support. At our respiratory intensive care unit (RICU), the ventilatory treatment
      of ACRF has, for many years, been based on a conservative method, which relies on
      the use of a body ventilator (iron lung) providing intermittent negative pressure
      ventilation (INPV). From 1975 to 1991, we treated ACRF in 2,116 patients with
      chronic obstructive pulmonary disease (COPD) and 604 patients with restrictive
      thoracopulmonary disease (RTD). Two thousand and eleven patients (95%) underwent
      INPV. The mortality rate during hospitalization was 9.9% for the patients as a
      whole (10% and 8.9% for COPD and RTD patients, respectively). The mean length of
      stay in the RICU was 10.5 +/- 9.5 days. Furthermore, we report the results of our
      previous studies which investigated how the iron lung works, and how it affected
      the short- and long-term prognosis of COPD patients in ACRF. Finally, in 180
      patients, we report the effects of INPV provided by iron lung on the treatment of
      ACRF with hypoxic hypercapnic coma (HHC). INPV resulted in a significant
      improvement of arterial blood gas values and pH, associated with a progressive
      recovery of the level of consciousness. Only 13 patients needed intubation and 41
      (23%) died during hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711716
TI  - Different modes of noninvasive intermittent positive pressure ventilation (IPPV)
      in acute exacerbations of COLD patients.
AB  - Patients with chronic obstructive lung disease may suffer from acute
      exacerbations of their disease, which may lead to acute respiratory failure
      necessitating endotracheal intubation and mechanical ventilation. We have
      compared retrospectively the results obtained with nasal positive pressure
      ventilation and those of standard medical therapy in acute relapses of severe
      COLD. The study showed that nasal IPPV (NIPPV) in control mode delivered for
      approximately 1 h, four times daily, six days a week over a 21 day period, does
      not result in independent improvement of acute exacerbation of COLD. In the next
      study the data seem to indicate, in apparent contrast, a marked reduction in the
      need for endotracheal intubation using noninvasive ventilation, both with assist
      control and pressure support noninvasive modes, in comparison with an historical
      control group. We did not find a significant difference in the success rate of
      the two modes, but compliance to noninvasive ventilation was better with pressure
      support. In the former study patients showing neurological signs and requiring
      mechanical ventilation were excluded, while in the last study patients were
      selected on the basis of necessity of mechanical ventilation. The fact that in
      the last study, ventilation was applied by face mask instead of nasal mask may
      have influenced results. Further efforts are required to determine whether non
      invasive ventilation is more a preventive measure to avoid endotracheal
      intubation, or is another means of delivering ventilatory support.

PMID- 7711717
TI  - Acute respiratory failure, due to severe obstructive sleep apnoea syndrome,
      managed with nasal positive pressure ventilation.
AB  - The complications of endotracheal intubation are particularly frequent in
      patients with obstructive sleep apnoea syndrome (OSAS). We prospectively tested
      nasal ventilation in such patients admitted for acute respiratory failure. Six
      consecutive patients, aged 17-70 yrs, were selected for the study. All patients
      were confused or severely obtunded, Glasgow Coma Score (GCS) 10 (SD 2). With
      nasal bi-level positive airways pressure (BiPAP) all these patients improved
      clinical status and arterial blood gas values, avoiding intubation and invasive
      mechanical ventilation. The median pH increased from 7.26 (SD 0.06) to 7.36
      (0.01) and to 7.43 (0.02) after, 1-3 and 24 h of nasal ventilation, respectively.
      Nasal ventilation lasted an average of 21 (3) h on the first day. All patients
      were discharged home after a median hospital stay of 28 (11) days.

PMID- 7711718
TI  - Impact of heat and moisture exchangers on ventilatory pattern and respiratory
      mechanics in spontaneously breathing patients.
AB  - The upper airways warm and saturate inspired air with water vapour. In intubated
      or tracheotomized patients, this function is replaced either by hot water
      humidifiers or by heat and moisture exchangers (HMEs). The aim of this study was
      to quantify the modifications of ventilatory mechanics and patients' work when
      two different HMEs were added to spontaneously breathing patients. We studied
      nine consecutive patients with no previous history of chronic obstructive lung
      disease. All patients had been weaned from mechanical ventilation. They were
      breathing through devices supplying positive end-expiratory pressure and/or O2
      enrichment. Two different HMEs were used: Icor Mediflux 1 and Icor Mediflux 2.
      These HMEs have identical chemical composition and configuration, but the
      Mediflux 1 is larger than the Mediflux 2. The humidification of the inspired
      gases was obtained alternatively by an active humidifier and the two HMEs. Data
      regarding ventilatory pattern and respiratory mechanics were collected by
      pulmonary monitor CP100 (Bicore). Tidal volume, work of breathing and pressure
      time product were greater with Mediflux 1 than with Mediflux 2 or active
      humidifier. There were no significant differences in respiratory rate, intrinsic
      positive end-expiratory pressure (PEEPi), rapid shallow breathing index, arterial
      CO2 and O2 partial pressure. The larger HME (Mediflux 1) increased patient's
      effort, with no evidence of patient discomfort. However, the smaller HME
      (Mediflux 2) did not add a detectable load and provided adequate humidification.
      In conclusion, the smaller HME appears to be preferable for the management of
      spontaneously breathing patients.

PMID- 7711719
TI  - Spirometry and lung transplantation.

PMID- 7711720
TI  - Somatic mosaicism, germline expansions, germline reversions and intergenerational
      reductions in myotonic dystrophy males: small pool PCR analyses.
AB  - In order to characterize the dynamics of CTG repeat instability in somatic and
      germline tissue from myotonic dystrophy (DM) males we have used small pool
      polymerase chain reaction (PCR) in a detailed quantitative analysis of repeat
      length variation. We demonstrate that the heterogeneous smear of CTG repeats
      observed in DM patients using standard analyses is comprised of multiple
      unresolved bands that may be dissected into discrete length alleles derived from
      single cells using single molecule PCR techniques. Analysis of somatic tissues
      demonstrates a bias toward increasing allele length and a lower boundary below
      which variant alleles are rare, consistent with a highly directional expansion
      pathway in the soma. Two sperm samples show extensive variation and a size
      increase bias, concordant with the phenomenon of anticipation. In addition, sperm
      analysis shows that large contractions, including reversions into the normal size
      range, are restricted to the germline. Detailed analysis of intergenerational
      'reductions' paternally transmitted to two offspring suggests that some apparent
      reductions may be artifacts of somatic expansion in the parent. Our data indicate
      that in addition to germline variation, substantial somatic expansion can also
      contribute to the intergenerational differences usually observed in DM.

PMID- 7711721
TI  - Localization of the gene for congenital dyserythropoietic anemia type III, CDAN3,
      to chromosome 15q21-q25.
AB  - Congenital dyserythropoietic anemia, type III (CDA III) is a rare autosomal
      dominant disorder characterized by macrocytic anemia, bone marrow erythroid
      hyperplasia and giant multinucleate erythroblasts. We have genetically
      characterized a large Swedish family in which the concurrence of CDA III and
      myeloma or benign monoclonal gammopathy is significantly higher than expected and
      have found that the causative genetic defect for CDA III maps to an 11 cM
      interval within 15q21-q25.

PMID- 7711722
TI  - Localization to chromosome 7q36.1 of the human XRCC2 gene, determining
      sensitivity to DNA-damaging agents.
AB  - The identification of genes controlling cellular response to DNA damage is of
      considerable importance, and cell lines showing hypersensitivity to DNA-damaging
      agents can be used as vehicles to map and clone these genes. In this study the
      hamster cell line irs1, showing hypersensitivity to a number of different DNA
      damaging agents, was fused to normal human cells to complement the defect. The
      resultant hybrids were analysed by Alu-PCR, chromosome painting, and with DNA
      markers to map the complementing gene (named XRCC2) to a specific chromosomal
      region. These hybrids showed correction of sensitivity to both X-rays and to
      mitomycin-C, and contained human chromosome 7, often as their only human
      component. Hybrids showing unstable retention of human chromosomes were sub
      cloned to show that loss of chromosome 7 and loss of resistance to mitomycin-C
      occurred concordantly. Two separate hybrids were found to have a smaller piece of
      chromosome 7, and specific DNA probes and microsatellite markers defined this as
      a contiguous region at 7q35-36. Hybrid irradiation-fusion methods were used to
      further reduce the size of the complementing genomic region and to localize the
      gene to an approximately 3-5 Mb region at 7q36.1.

PMID- 7711723
TI  - Evidence of a locus for orofacial clefting on human chromosome 6p24 and STS
      content map of the region.
AB  - Orofacial clefting is genetically complex, no single gene being responsible for
      all forms. It can, however, result from a single gene defect either as part of a
      syndrome (e.g. van der Woude syndrome, Treacher-Collins syndrome, velo-cardio
      facial syndrome) or as an isolated phenotypic effect (e.g. X-linked cleft palate;
      non-syndromic, autosomal dominant orofacial clefting). Several studies have
      suggested that chromosome 6p is a candidate region for a locus involved in
      orofacial clefting. We have used YAC clones from contigs in 6p25-p23 to
      investigate three unrelated cases of cleft lip and palate coincident with
      chromosome 6p abnormalities. Case 1 has bilateral cleft lip and palate and a
      balanced translocation reported as 46,XY,t(6,7)(p23;q36.1). Case 2 has multiple
      abnormalities including cleft lip and palate and was reported as
      46,XX,del(6)(p23;pter). Case 3 has bilateral cleft lip and palate and carries a
      balanced translocation reported as 46,XX,t(6;9)(p23;q22.3). We have identified
      two YAC clones, both of which cross the breakpoint in cases 1 and 3 and are
      deleted in case 2. These clones map to 6p24.3 and therefore suggest the presence
      of a locus for orofacial clefting in this region. The HGP22 and AP2 genes,
      potentially involved in face formation, have been found to flank this region,
      while F13A maps further telomeric in 6p24.3/25.

PMID- 7711724
TI  - Fine deletion mapping on the long arm of chromosome 9 in sporadic and familial
      basal cell carcinomas.
AB  - Basal cell carcinomas (BCCs) are the most common sporadic cancers worldwide. They
      are also a cardinal manifestation of a familial cancer predisposition syndrome,
      naevoid BCC syndrome (NBCCS). The gene responsible for NBCCS is likely to be a
      tumour suppressor gene and has been genetically mapped to a 2cM region between
      microsatellite markers, D9S196 and D9S180 at 9q22.3-q31. 101 BCCs (63 sporadic
      and 38 familial) were examined for loss of heterozygosity (LOH) in the candidate
      region of the NBCCS gene. Deletions were found in 46% and all LOH is consistent
      with genetic mapping of the NBCC locus. These findings strongly support the
      hypothesis that inactivation of the putative tumour suppressor, the NBCCS gene,
      is important in the formation of sporadic BCCs. One sporadic tumour indicates
      that the smallest region of overlap of these deletions is within the interval
      between D9S287 and D9S180. If this is confirmed in additional tumours, it would
      further narrow down the NBCCS region and exclude one candidate gene, that for the
      C complementation group of Fanconi anaemia, which maps proximally to D9S287.
      However, it would not exclude another candidate, the gene for the A
      complementation group of xeroderma pigmentosum (XPAC). Evidence of imprinting was
      also sought but preliminary data indicate that it is unlikely to occur at the
      NBCCS locus.

PMID- 7711725
TI  - A novel repeat structure at the myotonic dystrophy locus in a 37 repeat allele
      with unexpectedly high stability.

PMID- 7711726
TI  - High frequency of nonsense mutations in the NF2 gene caused by C to T transitions
      in five CGA codons.

PMID- 7711727
TI  - Novel frameshift mutations in the procollagen 2 gene (COL2A1) associated with
      Stickler syndrome (hereditary arthro-ophthalmopathy).

PMID- 7711728
TI  - Deficiency of lecithin:cholesterol acyltransferase due to compound heterozygosity
      of two novel mutations (Gly33Arg and 30 bp ins) in the LCAT gene.

PMID- 7711729
TI  - Expression of the mutant allele of IT-15 (the HD gene) in striatum and cortex of
      Huntington's disease patients.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disorder expressed
      when a trinucleotide repeat in the gene IT-15 is expanded. The mechanism by which
      the expanded repeat causes the expression of the disease is unknown. Possible
      mechanisms include alterations in the amount of the mRNA, potentially resulting
      from changes in gene transcription or abnormal mRNA stability. In order to
      determine whether the expanded IT-15 allele is present in mRNA, we isolated total
      RNA from the cortex and striatum of patients and controls. To distinguish the two
      alleles of the IT-15 transcript in HD patients, we amplified across a region
      containing a dimorphic single triplet deletion observed on some chromosomes and
      found that the relative intensity of the two PCR bands amplified from genomic DNA
      and those amplified from first strand cDNA from brain tissue were essentially
      equal. In order to determine whether the exon containing the expanded CAG repeat
      is present in IT-15 mRNA from HD patients, we amplified across this region and
      demonstrated the presence of the expanded repeat in cDNA from both striatum and
      cortex. Based on this evidence, we suggest that the mechanism of disease
      expression does not occur during transcription or in the stability of the RNA,
      but rather occurs during translation or postranslationally.

PMID- 7711730
TI  - Carnitine palmitoyltransferase II deficiency: structure of the gene and
      characterization of two novel disease-causing mutations.
AB  - Carnitine palmitoyltransferase (CPT) II deficiency is the most common inherited
      disorder of lipid metabolism affecting skeletal muscle. To facilitate the
      identification of disease-causing mutations in the CPT II gene (CPT1), we have
      established the genomic organization of this gene. CPT1 spans approximately 20 kb
      of 1p32 and is composed of five exons ranging from 81 to 1305 bp. The sequences
      of the exon--intron boundaries were determined for each exon and conformed to the
      consensus splice junction sequences. The 5' and 3' untranslated regions in exon 1
      and 5, respectively, were also determined, including the polyadenylation signal
      and the polyadenylation site. The mature transcript is predicted to be 3090 nt in
      length. CPT1 exons from CPT II-deficient patients were amplified and directly
      sequenced. Two novel disease-causing mutations were identified and characterized.
      The first mutation was a C-665-to-A transversion in exon 1 resulting in a proline
      to-histidine substitution at residue 50 of the protein (P50H). This amino acid
      substitution occurs within a leucine-proline motif that is highly conserved in
      acyltransferases from different species. The mutation was detected in both
      alleles of patient 05SB of Italian ancestry, and in one allele of patients 11EG,
      38PG, and 26FD of Italian, Dutch, and French ancestry, respectively. The second
      mutation was a rare G-2173-to-A transition in exon 5 causing an aspartic-acid-to
      asparagine substitution at amino acid 553 (D553N) and the generation of a new
      MseI site. The mutation was detected only in one allele of patient 15MB, of
      Italian ancestry, who was also heterozygous for the common S113L substitution.
      Transfection experiments in COS cells demonstrated that both mutations
      drastically depressed the catalytic activity of CPT II. Biochemical
      characterization of P50H mutant CPT II in cultured cells from patient 05SB showed
      that the mutation does not affect substrate binding sites. Finally, immunoblot
      analysis demonstrated that both mutations were associated with markedly reduced
      steady-state level of the protein, thus indicating decreased stability of the
      mutant CPT II.

PMID- 7711731
TI  - Molecular dissection of a contiguous gene syndrome: localization of the genes
      involved in the Langer-Giedion syndrome.
AB  - The Langer-Giedion syndrome (tricho-rhino-phalangeal syndrome type II, TRPS II)
      is characterized by craniofacial dysmorphism and skeletal abnormalities. It
      combines the clinical features of TRPS I and multiple cartilaginous exostoses
      (EXT). We have used YAC cloning, Southern blotting, PCR analysis, and
      fluorescence in situ hybridization to study chromosome 8 deletions,
      translocations, an inversion, and an insertion in patients with TRPS I, TRPS II
      or EXT. Our results indicate that the TRPS gene maps more than 1,000 kb proximal
      to the EXT1 gene and that both genes are affected in TRPS II. We conclude that
      TRPS II is not due to pleiotropic effects of mutations in a single gene, but that
      it is a true contiguous gene syndrome.

PMID- 7711732
TI  - Analysis of 2166 clones from a human colorectal cancer cDNA library by partial
      sequencing.
AB  - Large scale sequencing of cDNAs from a tissue-specific library provides
      information on the functional phenotype of that tissue and the clones constitute
      a reservoir of biological markers. For these reasons, we have randomly sequenced
      2166 clones of a cDNA library constructed with human colorectal cancer mRNAs.
      Database searches indicated that 1014 of the cDNAs represented known human genes
      or human homologs of other genes, 142 sequences corresponded to known ESTs, 119
      sequences corresponded to 28S rRNA, repetitive sequences or poly(A) stretches
      only, and 891 corresponded to unknown transcripts representing the products of
      740 new genes. Preliminary studies demonstrated that expression of some of them
      was altered in cancer. That cDNA collection is therefore a source of potential
      markers of colorectal cancer.

PMID- 7711733
TI  - Hotspot for deletions in the CGG repeat region of FMR1 in fragile X patients.
AB  - The fragile X syndrome is the most frequent cause of inherited mental
      retardation. The molecular mechanism of the disorder is based on the expansion of
      a CGG repeat in the 5' UTR of the FMR1 gene in the majority of fragile X
      patients. The instability of this CGG repeat containing region is not restricted
      to the CGG repeat itself but expands to the flanking region as well. We describe
      four unrelated fragile X patients that are mosaic for both a full mutation and a
      small deletion in the CGG repeat containing region. Sequence analysis of the
      regions surrounding the deletions showed that both the (CGG)n repeat and some
      flanking sequences were missing in all four patients. The 5' breakpoints of the
      deletions were found to be located between 75-53 bp proximal to the CGG repeat.
      This suggests the presence of a hot spot region for deletions in the CGG repeat
      region of the FMR1 gene and emphasizes the instability of this region in the
      presence of an expanded CGG repeat.

PMID- 7711734
TI  - DNA-based mutation analysis of Bruton's tyrosine kinase gene in patients with X
      linked agammaglobulinaemia.
AB  - The identification of the BTK (Bruton's tyrosine kinase) gene defective in human
      immunoglobulin deficiency X-linked agammaglobulinaemia (XLA) and characterisation
      of BTK exon-intron boundaries has now allowed the analysis of mutations and
      polymorphisms at the level of genomic DNA. Using Southern blot analysis and the
      polymerase chain reaction single strand conformation polymorphism (PCR-SSCP)
      assay, amplifying all 19 exons and the putative promoter region with a single
      annealling temperature, mutations have been identified in 19 out of 24 unrelated
      patients diagnosed as having XLA. Apart from a large deletion involving exon 19,
      nine missense (F25S, R288W, 1370M, M509V, R525P, N526K, R562W, A582V and G594R),
      two nonsense (E277X and R525X), five frameshift and two splice site mutations
      have been found affecting most coding exons and all major enzyme domains. No
      mutations or polymorphisms were detected in the putative promoter region. A
      single nucleotide deletion located in the last exon, resulting in a truncation of
      the eight C-terminal residues of Btk and a typical XLA phenotype, indicates
      structural and/or functional importance of Btk helix I in the catalytic domain.
      Although allelic heterogeneity at the BTK locus may partly explain clinical
      variability in families with XLA, compensatory and redundant mechanisms involved
      in B-cell development must play a role in the phenotypic diversity of the
      disease.

PMID- 7711735
TI  - Integration of physical, breakpoint and genetic maps of chromosome 22.
      Localization of 587 yeast artificial chromosomes with 238 mapped markers.
AB  - Detailed physical maps of the human genome are important resources for the
      identification and isolation of disease genes and for studying the structure and
      function of the genome. We used data from STS content mapping of YACs and natural
      and induced chromosomal breakpoints to anchor contigs of overlapping yeast
      artificial chromosome (YAC) clones spanning extensive regions of human chromosome
      22. The STSs were assigned to specific regions (bins) on the chromosome using
      cell lines from a somatic hybrid mapping panel defining a maximum of 25
      intervals. YAC libraries were screened by PCR amplification of hierarchical pools
      of yeast DNA with 238 markers, and a total of 587 YAC clones were identified.
      These YACs were assembled into contigs based upon their shared STS content using
      a simulated annealing algorithm. Fifteen contigs, containing between 2 and 74
      STSs were assembled, and ordered along the chromosome based upon the cytogenetic
      breakpoint, meiotic and PFG maps. Additional singleton YACs were assigned to
      unique chromosomal bins. These ordered YAC contigs will be useful for identifying
      disease genes and chromosomal breakpoints by positional cloning and will provide
      the foundation for higher resolution physical maps for large scale sequencing of
      the chromosome.

PMID- 7711736
TI  - Genetic mapping of cleidocranial dysplasia and evidence of a microdeletion in one
      family.
AB  - Cleidocranial dysplasia (CCD) is an autosomal, dominantly inherited disorder of
      high penetrance affecting skeletal ossification and tooth development. Typically,
      affected individuals have hypoplastic/aplastic clavicles, patent fontanelles and
      sutures, supernumerary teeth, and short stature. We have used a candidate locus
      approach to map the responsible gene in two families with typical features of
      CCD. Linkage was established between CCD and four loci (D6S426, D6S451, D6S459,
      TCTE1) that span a region of 10 cM on chromosome 6p. A maximum lod score, Zmax,
      of 4.1 at a recombination fraction of zero was obtained at D6S451. One highly
      polymorphic microsatellite from this region (D6S459) showed allelic loss in all
      affected members of one family with two different sets of primers. The presence
      of a deletion in this area was confirmed by Southern blot analysis using a probe
      derived from the amplification product of the D6S459 marker. The data assign a
      gene for CCD to chromosome 6p21 and suggest that a microdeletion within an area
      of tight linkage to the CCD-phenotype has been identified.

PMID- 7711737
TI  - Mutations in the phosphorylase kinase gene PHKA2 are responsible for X-linked
      liver glycogen storage disease.
AB  - Phosphorylase kinase (PHK) is a key enzyme in the control of glycogen breakdown.
      Several types of PHK deficiency have been described of which X-linked liver
      glycogenosis type I (XLG I) is the most common. Since the XLG I locus and the
      gene encoding the liver alpha-subunit gene of PHK (PHKA2) have both been
      localized to Xp22, PHKA2 was a candidate gene for XLG I. In this study we
      identified four point mutations in four unrelated XLG I patients: three mutations
      introduce a premature stop codon, whereas the fourth mutation abolishes a splice
      site consensus sequence leading to exon skipping. These findings indicate that
      PHKA2 is the XLG I gene.

PMID- 7711738
TI  - Analysis of short tandem repeat (STR) allele frequency distributions in a
      Balinese population.
AB  - Genotypes for 53 short tandem repeat (STR) markers distributed at an average of
      39 cM intervals throughout the genome were determined for 46 individuals from the
      village of Bengkala, Bali. This village of approximately 2200 individuals has an
      oral and written tradition suggesting genetic bottlenecks. The allele frequency
      distributions in Bengkala were compared with distributions obtained by typing
      individuals in the CEPH data base using a Kolmogorov-Smirnov two sample test.
      Twenty-eight of the 53 markers showed differences (P < 0.05) in distribution
      between the two populations. Allele frequencies of tetranucleotide STRs were much
      more similar between the two populations than were those of dinucleotide STRs (P
      < 0.043). Population heterogeneity in Bengkala was indicated by an excess of
      observed homozygosity, deviations from Hardy-Weinberg equilibrium at seven loci,
      and significant allelic associations between physically unlinked loci. In
      addition to providing information pertinent to the issue of genetic diversity of
      STRs in the human population, these analyses serve as a resource to map a gene
      causing non-syndromal autosomal recessive deafness in Bengkala, and to
      corroborate the anthropological study of the history and social structure of the
      village.

PMID- 7711739
TI  - Use of a DNA pooling strategy to identify a human obesity syndrome locus on
      chromosome 15.
AB  - Bardet-Biedl syndrome is a heterogeneous autosomal recessive disorder
      characterized by obesity, mental retardation, polydactyly, retinitis pigmentosa
      and hypogonadism. Patients with this disorder also have a high incidence of
      hypertension, diabetes mellitus, and renal and cardiovascular anomalies. Three
      independent loci causing Bardet-Biedl syndrome have previously been reported. In
      this study, we we utilized a DNA pooling approach using DNA samples from a highly
      inbred Bedouin kindred to identify a new Bardet-Biedl syndrome locus on
      chromosome 15. The results further demonstrate the genetic heterogeneity of this
      disorder. In addition, the results demonstrate the efficiency of the DNA pooling
      approach for identifying recessive disease loci in highly inbred human
      populations.

PMID- 7711740
TI  - Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q.
AB  - Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal
      recessive disorders with combined visual and hearing loss. Type I (USH1) is
      characterized by a congenital, severe to profound hearing loss and absent
      vestibular function; in type II (USH2) the hearing loss is congenital and
      moderate to severe, and the vestibular function is normal. Progressive pigmentary
      retinopathy (PPR) is present in both types. A third type (USH3) differing from
      USH2 by the progressive nature of its hearing loss has been suggested. USH3 has
      previously been estimated to comprise 2% of all USH. However, based on clinical
      criteria, in Finland 42% of USH patients have progressive hearing loss suggesting
      enrichment of an USH3 gene. We excluded the four previously mapped USH regions as
      the site of the USH3 disease locus. Systematic search for USH3 by genetic linkage
      analyses in 10 multiple affected families using polymorphic microsatellite
      markers revealed significant linkage with markers mapping to chromosome 3q.
      Pairwise lod scores at zero recombination distance were 7.87 for D3S1308, and
      11.29 for D3S1299, incorporating the observed linkage disequilibrium.
      Conventional multipoint linkage analysis gave a maximum lod score of 9.88 at
      D3S1299 assigning USH3 to the 5 cM interval between markers D3S1555 and D3S1279
      in 3q21-25.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711741
TI  - Deletions of both alpha 5(IV) and alpha 6(IV) collagen genes in Alport syndrome
      and in Alport syndrome associated with smooth muscle tumours.
AB  - Diffuse oesophageal leiomyomatosis (DL), an inherited smooth muscle proliferation
      process, has been reported to be associated with Alport syndrome (AS), a familial
      nephropathy, mainly dominant X-linked inherited, and characterized by
      ultrastructural changes of the glomerular basement membrane. The COL4A5 gene,
      encoding the alpha 5 chain of type IV collagen, has been identified as the site
      of mutations in families with X-linked AS. Recently, a novel alpha 6(IV) collagen
      chain encoding gene has been mapped closely upstream of COL4A5, and disruption of
      the 5' end of both genes has been reported in four patients with DL and AS (DL
      AS). Here, we report a long-range restriction map around the COL4A6 locus, and
      show that the COL4A5/COL4A6 deletion observed in seven patients with DL-AS
      encompasses only the two first exons of COL4A6, with a breakpoint located in the
      second intron of COL4A6, whose size exceeds 65 kb. Furthermore, we demonstrate
      that three patients with AS without DL, known to have a deletion of the 5' part
      of the COL4A5 gene, display a larger deletion in COL4A6. Moreover, a COL4A6 mRNA
      product was detected by reverse-transcription-polymerase chain reaction in an
      oesophageal tumour sample of a patient with DL-AS. These results suggest that DL
      AS could be caused by an abnormal truncated alpha 6(IV) chain.

PMID- 7711742
TI  - Apolipophorin-III and adipokinetic hormone in lipid metabolism of larval Manduca
      sexta.
AB  - The hemolymph lipid levels were measured and the density of lipophorin was
      determined during late larval development in Manduca sexta. During the feeding
      phase of the 4th and 5th instar larvae the lipid level in hemolymph remained
      largely unchanged at less than 2 mg/ml. During the molt from 4th to 5th instar,
      the hemolymph lipid level increased, but decreased after feeding restarted in the
      5th instar. In wandering larvae and prepupae the hemolymph lipid level increased
      from about 2 to nearly 10 mg/ml. The density of lipophorin from feeding larvae
      was found to be 1.148 g/ml with minor amounts of lipophorin having a lower
      density of about 1.128 g/ml and sometimes a small amount with a density of 1.174
      g/ml. In molting larvae, however, the density was clearly lower, 1.116 g/ml. In
      wandering larvae of all ages, two predominant forms of lipophorin were observed;
      the density of these forms was 1.132 g/ml and 1.177 g/ml. Rarely, one or three
      different forms of lipophorin were observed. While the lipophorin of feeding
      larvae contains only apoLp-I and II (and lipids), the lipophorin of molting
      larvae contains in addition apoLp-III. ApoLp-III is seldom present in lipophorin
      from wandering larvae. According to our current models, lipophorin can take up
      only a certain amount of diacylglycerol before it needs apoLp-III for surface
      stabilization. Injection of 1 pmol of M. sexta AKH into feeding larvae increased
      the hemolymph lipid level, decreased the density of lipophorin to 1.125 g/ml and
      resulted in the association of apoLp-III with lipophorin. Cardiacectomy did not
      prevent feeding larvae from developing to wandering larvae.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7711743
TI  - Identification of neuron-specific ivermectin binding sites in Drosophila
      melanogaster and Schistocerca americana.
AB  - High affinity avermectin binding sites have been identified and partially
      characterized in membranes from two insect species, Drosophila melanogaster and
      the locus Schistocerca americana. There is a 10-fold increase in the density of
      ivermectin binding sites associated with membranes isolated from Drosophila heads
      (a neuronally enriched tissue source) compared to the bodies (Bmax values were
      3.5 and 0.22 pmol/mg, respectively) with only a small difference in the apparent
      dissociation constant (Kd values of 0.20 and 0.34 nM for heads and bodies,
      respectively). Membranes prepared from metathoracic ganglia of the locust,
      Schistocerca americana, were highly enriched in high affinity avermectin binding
      sites (Kd = 0.2 nM and Bmax = 42 pmol/mg). Using an [125I]arylazido-avermectin
      analog as a photoaffinity probe, a 45 kDa protein was identified in both the
      Drosophila head and body tissue preparations. A 45 kDa protein was also
      specifically labeled with [125I]azido-avermectin in the locust neuronal
      membranes.

PMID- 7711744
TI  - Characterization of a spectrophotometric assay for juvenile hormone esterase.
AB  - Two surrogate substrates, methyl 1-heptylthioacetothioate (HEPTAT) and methyl 1
      hexylthioacetothioate (HEXTAT) were utilized to compare a new spectrophotometric
      assay with the standard radiochemical partition assay used to quantify juvenile
      hormone esterase (JHE) activity. The surrogate substrates were made with one
      common factor being a thiol ester moiety substituting for the ester moiety found
      in juvenile hormones (JHs) and a thioether replacing the 2,3-olefin of the JHs.
      As a result, nucleophilic attack by the serine residue of JHE at the carbonyl
      functional group results in a hydrolytic reaction and release of methanethiol. In
      the presence of Ellman's Reagent (DTNB) methanethiol will cleave the disulfide
      bond of DTNB resulting in a chromophore detectable at 405 nm. Methyl 1
      hexylthioacetothioate and its oxygen ester analogue, methyl-1-hexylthioacetate,
      were compared for JHE activity. Statistical analysis of the slopes indicated a
      very small but significant difference between the hydrolytic rates for the thiol
      ester and oxygen ester. However, the data indicate that thiol esters can replace
      oxygen esters to quantify hydrolytic activity by the JHEs examined. Results
      gathered from different preparations of JHE including tissue culture media from a
      baculovirus expression system, affinity- and DEAE-purified enzyme, as well as
      insect hemolymph indicate an excellent correlation between the two assays.
      Isoelectric focusing of pure and crude JHE preparations resulted in coinciding
      peaks of hydrolytic activity when using the standard partition assay and the
      spectrophotometric assay, with no other peaks of activity found in the crude
      preparations with either substrate. Several esterase bands were found at
      different isoelectric points when gels were stained with alpha-naphthyl
      acetate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711745
TI  - Structure and regulation of a gene cluster for male accessory gland transcripts
      in Drosophila melanogaster.
AB  - We characterize a cluster of three genes, named Mst57Da, Mst57Db and Mst57Dc,
      according to their localization at polytene band 57D and their selective
      expression in Drosophila melanogaster males. Within a 4 kb segment of genomic DNA
      these genes code for poly(A)+ RNAs of about 750 nt, 650 nt and 850 nt length that
      are restricted to the male accessory glands. They all contain relatively long 5'
      and 3' untranslated regions compared to the size of their open reading frames.
      The 5' untranslated regions are characterized by several short open reading
      frames. In addition, the genes Mst57Da and Mst57Db share a 14 nucleotides long
      conserved sequence block in front of the putative translated regions. We propose
      that these common features are structural elements important for translational
      control of these genes. The predicted sequences of the small proteins of 55, 40
      and 42 amino acids suggest that two of them (MST57Da and MST57Db) are secretory
      proteins and therefore components of the paragonial secretions. In P-element
      mediated germ line transformations of Mst57Db/lacZ fusion genes, a short gene
      fragment of -187/+395 is still specifically expressed in the paragonia. In
      addition, regions involved in negative and positive control of transcription have
      been identified. Development of a supernumerary paragonial gland is frequently
      observed in transgenic, intersexual genotypes indicating that in intersexes cells
      derived from the female genital disc can develop male genital structures.

PMID- 7711746
TI  - Gypsy moth midgut proteinases: purification and characterization of luminal
      trypsin, elastase and the brush border membrane leucine aminopeptidase.
AB  - The principal digestive proteinases of the gypsy moth, Lymantria dispar, larval
      midgut were identified, and the subcellular distribution of the enzyme activities
      was determined. Proteinase activities of fifth-instar larvae were largely
      attributed to two luminal serine proteinases, a trypsin-like enzyme (TLE) and an
      elastase 2-like enzyme (ELA). TLE was purified to homegeneity by benzamidine
      Sepharose affinity chromatography. With respect to size (M(r) = 25 kDa),
      substrate specificity, and interaction with trypsin inhibitors, the gypsy moth
      enzyme resembled mammalian pancreatic trypsin and trypsin-like enzymes from other
      insects. Gypsy moth elastase (ELA) was purified from the benzamidine-Sepharose
      flow-through by mono-Q FPLC. ELA exhibited a slightly smaller size (M(r) = 24
      kDa) than TLE. The insect enzyme was inhibited by DFP and chymostatin but was
      unaffected by TPCK. ELA exhibited little esterolytic activity with BTEE. Succinyl
      Ala-Ala-Pro-Leu p-nitroanilide was one of the best substrates for ELA, which is
      characteristic of elastase 2. TLE and ELA constituted c. 6% of the total soluble
      protein in midgut lumen of actively feeding fifth-instar larvae. Chymotrypsin and
      carboxypeptidase activities were not detected in any midgut fraction examined.
      The brush border membrane (BBM) leucine aminopeptidase (LAP) was isolated from
      CHAPS-solubilized BBM by FPLC. SDS-PAGE results indicated that the aminopeptidase
      has an apparent molecular size of c. 100 kDa. The aminopeptidase was inhibited by
      bestatin and was unaffected by serine proteinase inhibitors.

PMID- 7711747
TI  - Mosquito ecdysteroid receptor: analysis of the cDNA and expression during
      vitellogenesis.
AB  - An insect steroid hormone, 20-hydroxyecdysone (20E), plays an important role in
      regulating egg maturation in mosquitoes. To better understand its role, we cloned
      the cDNA coding for the putative ecdysteroid receptor from the mosquito, Aedes
      aegypti (AaEcR). The 4158 bp AaEcR cDNA has an open reading frame of 675 amino
      acids with 10 potential glycosylation sites and a putative phosphorylation
      polyserine domain. The AaEcR has a DNA binding domain with two zinc fingers and a
      ligand binding domain characteristic of members of the steroid hormone receptor
      superfamily. These AaEcR domains share 97 and 87% identities with the respective
      domains of the Drosophila ecdysteroid receptor (DmEcR). However, the A/B region
      of the AaEcR shares 35% identity with that of DmEcR-B1 isoform. The F region,
      located at the carboxyl-terminal of the AaEcR, has only 9% identity with the
      corresponding region of DmEcR. Potential nuclear targeting and dimerization
      signals are also present in the AaEcR sequence. There are three AaEcR transcripts
      of 4.2 kb, 6 kb and 11 kb in adult mosquitoes. 4.2 kb mRNA is predominantly
      expressed in female mosquitoes during vitellogenesis. In both the fat body and
      ovaries of the female mosquito, the level of AaEcR mRNA is high at the
      previtellogenic period and after the onset of vitellogenesis (6 h post blood
      meal, PBM).

PMID- 7711748
TI  - Insect cuticular proteins.
AB  - Insect cuticles are composite structural materials with mechanical properties
      optimal for their biological functions. The bulk properties of cuticles are to a
      large extent determined by the interactions between the various components,
      mainly the chitin filament system and the proteins. The various cuticular types
      show pronounced differences in mechanical properties, and it is suggested that
      these differences can be related to the properties of the individual proteins and
      to the degree of secondary stabilization (sclerotization). The amino acid
      sequences, which have been obtained for insect cuticular proteins either by
      direct sequencing of purified proteins or by deduction from corresponding DNA
      sequences, are listed according to insect order and species. Extensive sequence
      similarity is observed among several cuticular proteins obtained from different
      insect orders. Other cuticular proteins are characterized by repeated occurrence
      of a few small motifs consisting mainly of hydrophobic residues. The latter group
      of proteins has so far only been reported from stiff cuticles. The possible
      relevance of the various motifs and repeats for protein interaction and the
      mechanical properties of cuticles is discussed.

PMID- 7711749
TI  - Comparison of larval and pupal cuticular proteins in Tenebrio molitor.
AB  - Protein extracts from pupal and larval pharate cuticle from the meal worm,
      Tenebrio molitor, gave nearly identical patterns by two-dimensional
      electrophoresis and by ion-exchange chromatography. The main components in the
      cuticular extracts from the two metamorphic stages were also identical with
      respect to molecular mass according to electrospray ionization mass spectrometry.
      The complete amino acid sequence for one of the pupal cuticular proteins was
      determined; according to partial amino acid sequences and the mass spectrometric
      peptide map for the corresponding larval cuticular protein, it was concluded that
      the larval protein has the same amino acid sequence as the pupal protein. The
      sequence is characterized by a high content of alanine, proline, valine, and
      tyrosine and the complete absence of acidic amino acid residues, the sulphur
      containing amino acids and tryptophan. The sequence is further characterized by a
      high frequency of repeated sequence motifs, among which the Ala-Ala-Pro-Ala motif
      is the most abundant, but also longer sequence motifs are repeated. The sequence
      shows striking resemblance to sequences of proteins isolated from pharate locust
      cuticle.

PMID- 7711750
TI  - A Drosophila male accessory gland protein that is a member of the serpin
      superfamily of proteinase inhibitors is transferred to females during mating.
AB  - Accessory gland peptide 76A, (Acp76A), belongs to the serpin superfamily of
      proteins (serine protease inhibitors). Acp76A is a secreted protein synthesized
      only in the Drosophila melanogaster adult male accessory gland. Accumulation of
      the protein in males is first detected with polyclonal antibodies at 1 day after
      eclosion. The level of the protein in virgin males reaches a peak 5-8 days post
      eclosion, and remains constant for at least 20 days. Upon mating the amount of
      Acp76A in males drops dramatically, but recovers by 24 h after mating.
      Immediately after mating the Acp76A is found in the female uterus. By 6 h after
      mating the amount of Acp76A detected in females is drastically reduced.

PMID- 7711751
TI  - Purification and properties of glycogen phosphorylase from the fat body of larval
      Manduca sexta.
AB  - Glycogen phosphorylase b has been purified to homogeneity from the fat body of
      larval Manduca sexta. The purification procedure involved ammonium sulfate
      precipitation, and chromatography of DEAE-cellulose, 5'-AMP-Sepharose and Q
      Sepharose. The final product, which showed a single band on SDS-PAGE with a M(r)
      = 92,500, was purified 50-fold from the original homogenate in a yield of about
      3%. The molecular mass of the native purified phosphorylase b was estimated to be
      186,000 Da from gel filtration, suggesting that the native enzyme is a dimer. The
      apparent Km values for glycogen, phosphate and 5'-AMP were 1.4 mM, 82 mM and 1.1
      mM, respectively. The enzyme had a pH optimum of 7.05, and was inhibited by ATP,
      ADP and glucose, but not by trehalose, even at high concentration. Conversion of
      phosphorylase b into the a form was achieved by incubation with rabbit
      phosphorylase kinase and Mg(2+)-ATP. The molecular mass of phosphorylase a was
      estimated to be 250,000 Da by gel filtration chromatography. The specific
      activity of the a form in the presence of 5'-AMP was 1.6-1.7-fold higher than the
      specific activity of the b form under the same conditions. Thus, 5'-AMP activates
      the a form by about 20%, whereas ATP has no effect on the phosphorylase a
      activity.

PMID- 7711752
TI  - Rapid and efficient isolation of transferrin and ferritin from Manduca sexta.
AB  - We report methods for the rapid purification of two iron-binding proteins from
      larval hemolymph of Manduca sexta. Ferritin was purified in two steps by density
      gradient ultracentrifugation. To accomplish this, we utilized the relatively high
      level of ferritin present in the hemolymph of this animal and augmented the
      density of the protein in vivo by injection of iron sulfate. Nitrocellulose blots
      analyzed by laser densitometry showed hemolymph from iron-injected insects
      contained about 0.4 mg of ferritin per ml (approximately 0.7% of total hemolymph
      protein); of this, 62% was found as pure ferritin in the pellet formed during
      ultracentrifugation. Following the density ultracentrifugation, we purified
      transferrin from the hemolymph subphase by immobilized metal ion affinity
      chromatography using a new gel, Novarose-SE1000/40 coupled to dipicolylamine
      (DPA) chelated with nickel. Higher capacity Ni2+DPA-gel permitted good resolution
      of transferrin in the first chromatography; a lower capacity of the same gel
      allowed purification of transferrin in a second step. Overall transferrin
      recovery was 52%. Larval hemolymph contained 0.770 mg transferrin/ml,
      representing about 1.3% of the total protein.

PMID- 7711753
TI  - Origin of arachidonic acid in the salivary glands of the lone star tick,
      Amblyomma, americanum.
AB  - The contribution of synthesis and dietary sequestration to the high arachidonate
      content of the lone star tick, Amblyomma americanum, salivary glands was
      investigated by assessing the salivary metabolites of various radiolabeled fatty
      acid substrates administered to partially fed females. A portion of each of the
      fatty acids studied was incorporated into the fatty acid moiety of the
      phospholipid fraction. [14C]acetate was metabolized only into myristic, palmitic,
      palmitoleic, steric, and oleic acids. [3H]oleic acid, [14C]linoleic acid,
      [14C]gamma-linolenic acid and [14C]eicosatrienoic acids were incorporated into
      salivary gland phospholipids but underwent little change including elongation
      and/or desaturation to arachidonate. Ingested [3H]arachidonic acid was readily
      taken up by the salivary gland and distributed among the lipid classes in a
      pattern markedly different from that of the other fatty acids tested. We conclude
      that ticks are unable to synthesize arachidonic acid for incorporation into the
      salivary glands, but rather sequester it from the host bloodmeal.

PMID- 7711754
TI  - Early trypsin activity is part of the signal transduction system that activates
      transcription of the late trypsin gene in the midgut of the mosquito, Aedes
      aegypti.
AB  - Trypsin activity during the first hours after feeding is essential to induce late
      trypsin gene expression. These results are consistent with the idea that free
      amino acids or other products released during digestion might be the initial
      signal for transcriptional activation of late trypsin. Besides early trypsin,
      some other factor(s) have to be translated for induction of late trypsin. This is
      the first case in which the proteolytic activity of a digestive enzyme is part of
      the signal transduction system which regulates expression of a second gene. The
      presence of two trypsins allows the mosquito to assess the quality of the meal
      and adjust the levels of late trypsin for a particular meal with remarkable
      flexibility.

PMID- 7711755
TI  - cDNA and deduced protein sequence of CYP6D1: the putative gene for a cytochrome
      P450 responsible for pyrethroid resistance in house fly.
AB  - A microsomal cytochrome P450 from the house fly (Musca domestica), termed
      P450lpr, is involved in P450 monooxygenase-mediated pyrethroid resistance and is
      expressed at 8-fold higher levels in the insecticide resistant LPR strain
      compared to a susceptible strain. An internal cDNA sequence was amplified by
      polymerase chain reaction (PCR) using degenerate primers based on known P450lpr
      polypeptide sequences, and the remainder of the sequence was amplified by single
      side-specific PCR. A 1.8 kb cDNA sequence was obtained from 3 overlapping PCR
      products, with an open reading frame encoding a P450 protein of 516 residues
      (M(r) 59,182). This gene has been designated CYP6D1 within the P450 gene
      superfamily. CYP6D1 exhibits most similarity (28.2-29.8% positional identity) to
      butterfly CYP6B1, house fly CYP6A1 and Drosophila CYP6A2, and also exhibits
      comparable similarity (24.7% identity) to rat CYP3A1. The deduced protein
      sequence contains a hydrophobic N-terminal region and conserved sequences thought
      to be involved in heme-binding and electron donor-protein interactions.
      Comparison of CYP6D1 with its four most similar proteins (CYP6B1, CYP6A1, CYP6A2
      and CYP3A1) reveals the presence of extensive stretches of residues in an
      alignment row in 2 possible substrate-binding regions. Three introns of 74, 66
      and 64 bp, having 5'-GT and AG-3' ends, split the CYP6D1 coding region in genomic
      DNA. Results indicate that CYP6D1 is likely the P450lpr gene.

PMID- 7711756
TI  - Regulation of serpin gene-1 in Manduca sexta.
AB  - Hemolymph of Manduca sexta contains proteins from the serpin superfamily, which
      are inhibitors of serine proteinases. We have used probes specific for M. sexta
      serpin gene-1 mRNA and protein to study the expression and hormonal regulation of
      this gene. Serpin gene-1 is expressed at a high level in larval fat body and at a
      lower abundance in hemocytes, where serpin protein is localized in the granules
      of granular cells. Serpin gene-1 mRNA is abundant in the fat body of feeding
      fourth and fifth instar larvae, but disappears abruptly at molts and at the
      wandering stage. The concentration of serpin proteins in hemolymph during
      development is correlated with the abundance of serpin mRNA in fat body. Results
      of in vivo and in vitro experiments indicate that 20-hydroxyecdysone has a role
      in negative regulation of serpin gene-1.

PMID- 7711757
TI  - The effect of substitutions at position three on the binding and bioactivity of
      proctolin in locust hindgut and oviduct.
AB  - A number of proctolin analogs modified at position three were analyzed for their
      relative binding affinities and biological activity on locust hindgut and
      oviduct. A decrease in chain length at this position (from Leu, Ile to Val) or an
      increase in hydrophobicity alone (Glu) or combined with a decrease in chain
      length (Val, Ser, Thr and Asp) decreased bioactivity but not necessarily binding.
      (Ser3)-proctolin had a higher affinity than proctolin for both hindgut and
      oviduct membranes but was less biologically active than proctolin in both
      tissues. Several other analogs bound with a similar affinity to proctolin but
      were significantly less biologically active, particularly on locust oviduct.
      These results suggest that the position three leucine of proctolin is more
      important for bioactivity than for binding in both oviduct and hindgut. The data
      also suggest the presence of two proctolin receptor subtypes on oviduct but not
      on hindgut membranes. Position three proctolin analogs may be useful in more
      precisely distinguishing these subtypes.

PMID- 7711758
TI  - A reliability study of measurement techniques to determine static scapular
      position.
AB  - Current shoulder rehabilitation programs encourage scapular stabilization
      components although, to date, no scientific studies have evaluated changes in
      scapular position following such rehabilitation. Four different measurement
      methods of scapular position have been reported in the literature. The purpose of
      this study was to examine the intratester and intertester reliability of these
      four methods and to also examine if significant differences exist in scapular
      position between dominant and nondominant extremities. Thirty-two subjects
      volunteered for this study. Intraclass correlation coefficients (ICC) revealed
      acceptable intratester reliability (ICC = 0.81-0.95) for all measurement methods.
      However, while one method also proved to be acceptable (ICC = 0.91-.92) for
      intertester measurements, the other three methods were unacceptable (ICC = 0.18
      0.69). One tester reported significant differences in scapular position of the
      dominant and nondominant extremities when using the most reliable method. The
      second tester found no significant differences with either method. Future
      research is recommended to reexamine reliability of these methods and measure
      subjects with shoulder pathology.

PMID- 7711759
TI  - The effect of velocity and gender on load range during knee extension and flexion
      exercise on an isokinetic device.
AB  - Limb acceleration and deceleration during exercise on an isokinetic device
      encounter no machine-offered resistance. The purpose of this study was to
      quantify the relationship between velocity and range of motion that is sustained
      at a predetermined isokinetic velocity, termed load range, during concentric knee
      extension and flexion exercise. Nine male and nine female subjects performed
      three maximal concentric reciprocal knee extension and flexion repetitions at 60,
      120, 180, 240, 360, and 450 degrees/sec. Extension and flexion results revealed a
      significant (p < 0.05) increase in acceleration and deceleration range of motion
      while load range significantly decreased with increasing velocity. Males
      exhibited greater load range and less acceleration range of motion than females
      at 240, 360, and 450 degrees/sec, while deceleration range of motion was not
      different between genders at any speed. These results demonstrate an inverse
      relationship between isokinetic velocity and load range and suggest a need to
      carefully consider velocity selection when performing exercise on an isokinetic
      device.

PMID- 7711760
TI  - Intertester reliability of measurements obtained with the KT-1000 on patients
      with reconstructed anterior cruciate ligaments.
AB  - Clinicians frequently measure anterior tibial displacement on patients following
      surgical reconstruction for a torn anterior cruciate ligament (ACL). Little is
      known about the reliability of measurements of anterior tibial displacement
      obtained on patients following an ACL reconstruction. The purpose of this study
      was to describe the degree of error associated with repeated measurements of
      anterior tibial displacement on patients with reconstructed ACLs. Random pairs of
      physical therapists used the KT-1000 to measure the anterior tibial displacement
      of 30 subjects. Each pair of examiners took measurements according to the
      manufacturer's instructions. Examiners took three sets of measurements while
      applying 6.8, 9.1, and 13.6 kg (15, 20, and 30 lbs) of force to the handle of the
      KT-1000. Intraclass correlation coefficients (ICC 2,1) and the standard error of
      the difference (SED) were calculated to describe the intertester reliability of
      the mean of three measurements of anterior tibial displacement at each force
      level and of the individual measurements at each force level. The SED was then
      multiplied by 2 to provide a 95% confidence estimate of the magnitude of error
      present with KT-1000 measurements. The SED estimates the magnitude of change in
      anterior tibial displacement necessary to infer that a real change in anterior
      tibial displacement has occurred. Clinicians can be 95% confident that changes in
      anterior tibial displacement of greater than 5 mm (+/- 2 SED) during KT-1000
      tests at 6.8, 9.1, or 13.6 kg (15, 20, or 30 lbs) of force indicate that a true
      change in anterior tibial displacement has occurred.

PMID- 7711761
TI  - Measurement of tibiofibular varum in subjects with unilateral overuse symptoms.
AB  - Lower extremity overuse injuries due to repeated microtrauma are often
      asymmetrical in nature. The purpose of this study was to determine if the amount
      of tibiofibular varum was asymmetrical in individuals with unilateral overuse
      injuries. The subjects were 20 patients who developed unilateral overuse symptoms
      of the leg and foot due to compensatory subtalar joint pronation. The distal one
      third of the leg was bisected with the subjects standing in their normal base of
      support. The angle of this bisection to vertical was measured with a fluid
      inclinometer to determine the amount of tibiofibular varum. This measurement was
      performed in relaxed calcaneal stance and subtalar joint neutral stance. A single
      examiner performed all of the measurements and was blinded to the side of the
      subject's symptoms. A two-way analysis of variance for repeated measures was
      performed. There was a significant difference in the amount of tibiofibular varum
      between the injured and the uninjured extremities. There was also a significant
      difference between the measurements of tibiofibular varum when comparing the
      resting calcaneal stance and the subtalar joint neutral stance positions. This
      difference in tibiofibular varum between the injured and uninjured extremities
      may be one example of an asymmetry that can cause unilateral overuse symptoms.

PMID- 7711762
TI  - The effects of proprioceptive ankle disk training on healthy subjects.
AB  - According to research, proprioceptive training enables injured subjects to reduce
      proprioceptive deficits and increase postural control. However, the effects of
      proprioceptive training have not been researched in healthy subjects. This study
      investigated the effects of Biomechanical Ankle Platform System (BAPS) training
      on postural sway of healthy subjects (N = 28). Subjects were pretested and
      posttested using the Kistler force platform while performing a single limb
      stance. The subjects stood on their dominant leg with the opposite hip and knee
      held in a self-selected position. Subjects trained the dominant leg three times
      per week for 10 weeks on the BAPS. Experimental subjects showed significant
      improvements in both the medial-lateral and anterior-posterior parameters of
      postural sway when compared with a control group. In conclusion, 10 weeks of
      proprioceptive ankle disk training significantly decreased postural sway in both
      the medial-lateral and anterior-posterior directions.

PMID- 7711763
TI  - Effect of positive heel inclination on posture.
AB  - Millions of women wear high heels on a daily basis; however, few studies have
      analyzed the changes high heels (positive heel inclination) have on posture. The
      purpose of this study was to determine whether positive heel inclination changed
      the postural alignment of the head, spine, pelvis, and knees. Fifteen female
      college students ((mean age = 22.7, SD = 3.7 years) had sagittal plane angles
      measured for the cervical spine, thoracic spine, lumbar spine, sacral spine, and
      knee joints in addition to anterior/posterior displacements of the head and
      pelvis. All variables were assessed by a Metrecom Skeletal Analysis System, a
      three-dimensional electrogoniometer. Six randomized trials, three at zero heel
      inclination and three at 5 cm positive heel inclination, were measured. Analysis
      of variance results indicated positive heel inclination of subjects brought about
      significantly lower anterior pelvic tilt, lumbar lordosis, and sacral base angles
      when compared with zero heel inclination (p < .01). Clinically, patients with low
      back pain may be affected by high heel usage because of the reduction of the
      normal lumbar lordosis.

PMID- 7711764
TI  - Mapping of limbic seizure progressions utilizing the electrogenic status
      epilepticus model and the 14C-2-deoxyglucose method.
AB  - We have previously described a model of limbic status epilepticus in which
      chronic prolonged seizure states of immobile, exploratory, minor convulsive or
      clonic convulsive behavior are induced by intracerebral electrical stimulation;
      these states appear to belong to the same behavioral progression as kindled
      seizures. We postulated that the underlying seizure substrates, as mapped by the
      14C-2-deoxyglucose method, should reflect a corresponding anatomic progression of
      discharge spread. Status epilepticus was induced in rat by pulsed-train current
      delivered for up to 90 min to one of several subcortical areas. Autoradiographs
      revealed that most of the observed patterns of seizure-induced metabolic
      activation comprised a hierarchical sequence, such that progressively more
      extensive patterns subsumed anatomic territories activated in less extensive
      patterns, thus allowing inferences as to the progression of discharge spread. In
      this sequence, the basolateral amygdala ipsilateral to the induction electrode
      was among the first structures to be activated. In successively larger activation
      patterns a small unilateral network related to basolateral amygdala was involved;
      this evolved through a transitional state to a unilateral extensive limbic
      pattern; which in turn was succeeded by bilateral extensive limbic activation.
      This hierarchical sequence culminated in a neocortical activation pattern, in
      which most of the forebrain was involved in intense seizure-induced activation.
      Seizure behaviors increased in severity in correspondence with the underlying
      seizure-activated anatomic substrate. In contrast, patterns of seizure activation
      were observed which did not fit within the early stages of the above sequence,
      although analysis indicates that the later stages of spread may be shared. The
      study of these patterns and those reported in the literature indicates that
      although limbic seizure networks may be anatomically distinct at their
      origination, further expansion is characterized by overlap; upon assumption of
      extensive patterns of activation the number of nuclei participating is so vast
      that the identity of the limbic originator is lost and common convulsive
      manifestations occur.

PMID- 7711765
TI  - Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and
      external pallidum in basal ganglia circuitry.
AB  - The subthalamic nucleus and the external pallidum (GPe) are classically viewed as
      part of the so-called indirect pathway, which acts in concert with the direct
      pathway. The direct and indirect pathways form the conceptual framework of the
      anatomical and functional organization of the basal ganglia. A review of recent
      data regarding the connections of the subthalamic nucleus and the GPe has
      revealed a lack of firm anatomical support for the existence of the indirect
      pathway. However, newly recognized projections of the subthalamic nucleus and the
      GPe place these structures on various novel routes that change the conceptual
      architecture of the basal ganglia circuitry. These new findings force us to
      modify our view of the functional identity of the subthalamic nucleus and the
      GPe. In this new perspective, the GPe stands as an additional integrative
      station, together with the striatum and the internal pallidum and substantia
      nigra pars reticulata (GPi/SNr), along the main steam of information processing
      within the basal ganglia circuitry. Because of its crucial position between the
      input and output stations of the basal ganglia, the GPe can markedly influence
      the neuronal computation that occurs at GPi/SNr levels. The subthalamic nucleus
      can still be regarded as a 'control structure' lying alongside the main stream of
      information processing. However, because of its widespread efferent projections,
      the subthalamic nucleus exerts its driving effect on most components of the basal
      ganglia. Its action is mediated not only by the indirect pathway, but by a
      multitude of mono- and polysynaptic projections that ultimately reach the basal
      ganglia output cells.

PMID- 7711766
TI  - Neurochemistry of the central vestibular pathways.
AB  - This review focuses on the neurochemistry of the central vestibular pathways. The
      main emphasis will be on the analysis of the central vestibular nuclei neurons,
      since several papers published in the past 5 years have provided important
      information on the role that neurotransmitter-dependent conductances play in the
      central processing of vestibular inputs. Indeed, increasing evidence suggests
      that both the non-linear intrinsic membrane properties of the neurons and the
      nature of the different neurotransmitters and neuromodulators involved in the
      vestibular network contribute to the various operations required for stabilising
      gaze and posture. It has also been demonstrated that the neurotransmitter
      dependent conductances together with the ionic voltage-dependent conductances may
      determine the firing patterns of the medial vestibular neurons and interfere with
      their integrative properties. We hope that this review will show that by
      combining in vitro and in vivo electrophysiological approaches and the new
      powerful neuropharmacological techniques developed from the recent advances of
      molecular biology, the vestibular system can be used as a good model to elucidate
      some of the basic properties of the brain including learning, neural computation,
      network reconfiguration and post-lesional plasticity.

PMID- 7711767
TI  - Implication of insulin-like growth factors in the pathogenesis of diabetic
      neuropathy.
AB  - Neuropathy can be a highly debilitating complication for about 10-15% of diabetic
      individuals. Unfortunately, the complex syndrome has proven difficult to explain
      and a consensus as to its cause has not emerged. It has recently come to light
      that insulin and insulin-like growth factors (IGFs) have neurotrophic actions on
      sensory, sympathetic and motor neurons. These are the main types of neurons
      afflicted in this disorder. Moreover, IGF activity is reduced in both clinical
      and experimental diabetes. The premise that insulin, IGF-I and IGF-II provide
      redundant neurotrophic support underlies the following new theory for
      pathogenesis of diabetic neural disturbances: a loss of insulin activity leads to
      a secondary partial decline in IGF-I activity. Although most of the redundant
      neurotrophic support is thereby eliminated, IGF-II activity continues to support
      the nervous system. The final enemy is time and the relentless age- and duration
      dependent run-down of IGF activity is suggested to contribute to the age- and
      duration-dependent neuropathy. Weight loss or anorexia nervosa are independent
      risk factors that can cause a rapid, painful neuropathy to develop as a result of
      a rapid loss of IGF activity. A distinguishing feature of this new theory is that
      hyperglycemia is not considered to be the main culprit. The following critical
      predictions from the theory were tested in diabetic rats: (i) IGF activity is
      reduced in diabetic neural tissues; (ii) conduction velocity is impaired in the
      diabetic spinal cord; (iii) replacement therapy with IGF can prevent neuropathy
      in diabetic nerves; and (iv) IGFs can prevent diabetic neuropathy, despite
      hyperglycemia. All of these predictions have been validated. It is hoped that a
      fresh perspective will stimulate renewed study into the causation of this most
      unfortunate disorder.

PMID- 7711768
TI  - Ototoxicity in developing mammals.
AB  - Developing mammals are more sensitive to noise, chemical and drug-induced
      ototoxicity than adults, with maximum sensitivity occurring during periods of
      anatomical and functional maturation of the cochlea. Normal physiological
      development of resting potentials (the endocochlear potential) and sound-evoked
      potentials including cochlear microphonics, summating potentials, compound action
      potentials, auditory brainstem responses and more recently distortion-product
      otoacoustic emissions have been characterized in several species including rats,
      mice, kittens, gerbils and guinea pigs. All of these responses are significantly
      impaired following acoustic trauma and/or exposure to a variety of ototoxic
      agents including aminoglycoside antibiotics, loop diuretics, antithyroid and
      antitumor drugs (alpha-difluoromethylornithine) and excitatory amino acids.
      Coupled with physiological and anatomical development is the maturation of
      specific biochemical pathways, which may be vulnerable targets of environmental
      noise and chemicals, excitatory amino acids and therapeutic drugs with ototoxic
      potentials.

PMID- 7711769
TI  - Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo
      cortical loop.
AB  - This paper reviews some of the recent findings on different aspects of the
      anatomical organization of the basal ganglia. Attempts have been made to
      delineate the anatomical substrate of information processing along the cortico
      basal ganglia-thalamo-cortical loop. Emphasis has been placed on data obtained
      with highly sensitive anterograde tract-tracing methods applied to the study of
      the main axis of the loop, which is composed of the striatum, the pallidum, and
      the substantia nigra. These findings have highlighted the complexities of the
      organization of the intrinsic basal ganglia circuitry, which comprises multiple
      modular units that are distributed according to highly ordered and repetitive
      patterns. Such an arrangement is well suited to convey cortical information in a
      highly specific manner throughout the basal ganglia. The basal ganglia circuitry
      is also designed so as to modulate in a precise manner the neuronal activity of
      several brain functional systems, which are involved in the direct control of
      different aspects of psychomotor behavior. Of utmost importance is the action of
      the basal ganglia on thalamocortical premotor neurons. It is through these
      neurons, which can be considered as a sort of final common pathway, that the
      basal ganglia ultimately influence the complex neuronal computation that goes on
      at cortical level.

PMID- 7711770
TI  - [88th French Congress on Urology. Paris, 16-18 November 1994. Program and
      abstracts].

PMID- 7711771
TI  - [Genital Ureaplasma diversum infection: investigations in cattle in France].
AB  - A first bacteriological study of infection by Ureaplasma diversum in cattle was
      performed in France on 50 bulls and 565 dairy cows. U diversum was isolated in
      74% (37/50) of the bull semen and 40% (227/565) of the cows. No significant
      relationship was found in cows between infection and lesions of granular
      vulvitis, nor between infection and breeding performances. Serological studies of
      isolates by membrane filtration dot immunobinding showed a predominance of the
      serogroups B and C in males, and serogroup B in females.

PMID- 7711772
TI  - The characteristics of redial generations in Lymnaea truncatula exposed to
      Fasciola hepatica miracidia after poisoning by sublethal doses of cupric
      chloride.
AB  - Adult Lymnaea truncatula were placed in a sublethal dose of copper chloride (0.1
      mg/l) for 1 h, and then in normal water before being exposed to a single Fasciola
      hepatica miracidium on the 2nd or 9th day of the experiment. Infection rates were
      higher in untreated snails and in snails infected 9 d after treatment (73.5 and
      71.4%) then in snails infected 2 d after copper contact (48.1%). Histological
      examination of surviving snail on the 30th day after miracidial exposure revealed
      that the total number of rediae was 25 and 31 per snail in snail groups infected
      2 and 9 d respectively after copper contact, and 44 in untreated controls. There
      was a drop in the number of live, free rediae in infected snails after treatment
      contact. This decrease was more marked in the first redial generation than in the
      first cohort of the second generation. These results reveal that the infection
      rate in snails and the redial burden of F hepatica were reduced by the copper
      treatment of snails before miracidial exposure but placement of survivors in
      water for 8 d after treatment limited the consequences of chemical toxicity.

PMID- 7711773
TI  - Partition of nitrogenous substances in the urine of sheep on different dietary
      protein intakes.
AB  - The distribution of nitrogenous substances in urine was studied in sheep fed high
      (28.71 g N daily) and low (9.32 g N daily) protein diets for 6-8 weeks. The
      concentrations of total nitrogen and urea, allantoin, free amino acids, uric
      acid, hippuric acid, creatinine, creatine and ammonia were measured in urine. The
      nitrogen content of these measured substances was calculated. The results showed
      that the concentrations of total urinary nitrogen and nitrogen of individual
      nitrogenous substances were lower in sheep on a low protein diet, except for uric
      acid nitrogen which was unchanged. Urea nitrogen was responsible for up to 74% of
      the total urinary nitrogen of both groups of animals without any significant
      difference. The individual nitrogen portions of nitrogenous substances other than
      urea in total urinary-N did not exceed 7% during the intake of both diets. The
      intake of a low protein diet resulted in a significant increase in the proportion
      of nitrogen from uric acid, hippuric acid, creatinine and free amino acids, while
      the fraction of ammonia nitrogen in the total urinary N was significantly
      reduced. It is concluded that different protein or nitrogen intake in the diet do
      not have any significant effect on the urea nitrogen fraction in the total
      urinary nitrogen of sheep.

PMID- 7711774
TI  - [Methods of study of the hepatitis C virus genome. Diagnostic tools in human
      pathology].
AB  - The study of the molecular biology of infectious agents involves the examination
      of their genomes and the products of those genomes. Molecular biology methods may
      therefore allow us to study either DNAs or RNAs. The study of genomic RNAs
      (viruses) or messenger RNAs (all infectious agents) is used increasingly in
      infectious disease pathology. The hepatitis C virus was identified in 1989 and
      was shown to be responsible for a large number of chronic hepatitis cases in
      France and worldwide. This virus is a good model for the development of
      technologies to study RNAs, which will later be applied to the study of other
      viruses. The molecular biology methods used to study hepatitis C virus RNA may be
      classified into 3 categories. a) Detection methods evidence nucleic acids in
      fluid or tissue samples, mainly using the polymerase chain reaction (PCR), but
      also newly developed techniques, such as the NASBA (nucleic-acid-sequence-based
      amplification), the Q-beta reaction, and the LCR (ligase chain reaction), and
      techniques that localize viral RNAs in tissue (in situ hybridization, in situ
      PCR). b) Quantitative methods determine the amount of RNA present in a sample.
      These include quantitative PCR and new technologies based on signal
      amplification, such as the 'branched DNA' assays which have recently been
      developed. c) Qualitative analysis of the genome uses genotyping methods to
      classify viral strains into different genotypes and subtypes.

PMID- 7711775
TI  - Response of milk yield, plasma cortisol, amino acids, urea and glucose to a
      single low-dose administration of adrenocorticotrophic hormone in lactating cows.
AB  - An experiment was conducted to determine the effects of a single low-dose
      administration of adrenocorticotrophic hormone (ACTH) on milk yield, plasma
      cortisol, free amino acids, urea and glucose in lactating cows. The animals were
      treated with either 6 IU synthetic ACTH or 5 ml physiological saline (control)
      administered intravenously via a jugular vein catheter. Blood was withdrawn 60
      and 5 min pretreatment (baseline), and 10, 20, 30, 60, 120, 180, 240, 300, 360,
      and 420 min post-treatment. A rapid positive response (P < 0.05) in plasma
      cortisol occurred within 10 min of administration of 6 IU ACTH. The maximum
      increase in plasma cortisol concentration occurred at 1 h post-ACTH treatment and
      plasma cortisol returned to baseline 4 h later. Until 7 d after ACTH
      administration, no effect on milk yield was recorded. In comparison with the
      saline-treated group, the ACTH-treated group exhibited a significant (P < 0.05)
      increase in the plasma concentrations of 3-methylhistidine, glycine, histidine,
      isoleucine, leucine, lysine, valine, and glucose. In contrast, the concentrations
      of alanine, aspartate, glutamate, glutamine and proline decreased significantly
      (P < 0.05) after ACTH treatment. Hormone administration had no effect on the
      plasma arginine, asparagine, methionine, phenylalanine, serine, threonine,
      tyrosine, and urea. These results demonstrate that the bovine species behaves
      like other mammalians with respect to its metabolic response to stress. Thus,
      during stress, ACTH increases adrenal cortical activity which, in turn,
      stimulates protein catabolism in muscle and gluconeogenesis from some non
      essential amino acids.

PMID- 7711776
TI  - [Antiseptic and antibiotic resistance of 310 gram-positive strains isolated from
      udders after use of post-milking teat germicides].
AB  - The sensitivity of 310 Gram-positive strains, isolated from milking cows udders,
      to 4 antiseptics (cetrimide, chlorhexidine, hexachlorophene and mercury) and 9
      antibiotics (ampicillin, streptomycin, erythromycin, chloramphenicol, kanamycin,
      tetracycline, gentamycin, novobiocin and oxacillin) was determined. The
      statistical analysis of correlation was carried out for the bacterial species
      studied (Staphylococcus, Streptococcus and Bacillus), the scattering of the
      minimum inhibitory concentrations of which has proved to be statistically
      heterogeneous towards antiseptics and antibiotics. This analysis revealed
      positive links between chlorhexidine and 5 antibiotics for Streptococcus and
      between hexachlorophene and oxacillin for Bacillus. The analysis of results at
      the level of bacterial species, taking into account a loss of sensitivity of 4
      times the modal minimum inhibitory concentration of the species reveals the
      importance of the strains which are resistant to many antibiotics and especially
      the Enterococcus and the species Staphylococcus epidermidis. Indeed, these
      strains are possible reservoirs of plasmids of resistance to antibiotics and
      antiseptics.

PMID- 7711777
TI  - Ecopathology in aquaculture: risk factors in infectious disease outbreak.
AB  - This paper describes a study of the risk factors associated with disease
      outbreaks in fish species of fish farms and rivers of north-east Spain. We
      focused our work on the isolation of fish pathogens (bacteria, virus), the water
      quality (physicochemical and microbiological quality) and management
      characteristics. We have observed 2 important viral diseases, infectious
      pancreatic necrosis and spring viraemia of carp, and 2 important bacterial ones,
      furunculosis (Aeromonas salmonicida) and bacterial kidney disease (BKD)
      (Renibacterium salmoninarum). Our preliminary results show that there are some
      potential risk factors associated with the main diseases of fish, such as fish
      age, fish species, production system, season and water temperature, but their
      role depends on the disease.

PMID- 7711778
TI  - Recovery of long-chain lipopolysaccharides from liquid culture of Actinobacillus
      pleuropneumoniae (serotype 5) for ELISA serodiagnosis.
AB  - Actinobacillus pleuropneumoniae (serotype 5) long-chain lipopolysaccharides (LC
      LPS) may be used as the antigen for ELISA serodiagnosis of pig pleuropneumonia. A
      method was developed in order to augment the recovery of this antigen compared to
      the previously described method. In liquid culture, A pleuropneumoniae was shown
      to produce 2.4 times more cells than in solid medium. LC-LPS could be recovered
      by phenol extraction of the crude extract. Only 1 additional phenol extraction
      was required to produce LC-LPS of the same quality as the one obtained with solid
      medium-grown cells, as revealed by SDS-PAGE and ELISA using reference sera. From
      the same volume of crude extract, approximately 8 times more antigen was present
      in the aqueous phase of the phenol extraction.

PMID- 7711779
TI  - Effects of vitamin E injection on body temperature and plasma alpha-tocopherol
      concentrations in pigs, lambs and calves.
AB  - Fifteen pigs, 15 lambs, and 15 calves were used to study the effect of
      supplementation of vitamin E on body temperature and plasma alpha-tocopherol
      concentrations following 1 intramuscular injection in 3 doses (1x, 3x, 5x). The
      1x doses for pig, lamb, and calf were 500, 1,000, and 1,500 IU, respectively.
      Data on body temperature and plasma alpha-tocopherol concentration were analyzed
      by least-squares procedures separately for each species. In each species plasma
      alpha-tocopherol concentration increased with increase in the dose of vitamin E
      injection, highest on d 1 postinjection and declined slowly throughout the
      remaining observation period. There was a transient elevation of body temperature
      on d 1 and 2 after injection in all species.

PMID- 7711780
TI  - Rehabbing Medicare. Is managed care a cure-all or just a crutch?
AB  - Money, or the prospect of saving it, is what's rallying many in Congress around
      supporting managed care as Medicare's magic bullet. And financial, as well as
      community, incentives are certainly helping to push Medicare managed care
      programs forward in the delivery system. But will those programs accomplish
      everything their advocates expect?

PMID- 7711781
TI  - Rediscovering my values.
AB  - Six years ago, Douglas Adams took a "dangerous detour" off his life's path,
      temporarily losing his way, ethically and professionally. What allowed him to
      regain his footing? A return to vision and values. In an essay that speaks to
      fundamental issues in the lives of executives in all fields, Adams retraces his
      steps and shows readers how he made his way back.

PMID- 7711782
TI  - Profiles in service (1986-1995). 1988 Foster G. McGaw prize winner: MetroHealth
      Medical Center, Cleveland, OH.
AB  - In the third of a series of features commemorating 10 years of the Foster G.
      McGaw Award, H&HN goes back to MetroHealth Medical Center, Cleveland, the 1988
      winner, to look at the financial, operational and strategic challenges that the
      public hospital faces today.

PMID- 7711783
TI  - MRI's second chance.
AB  - In the 1980s, magnetic resonance imaging was the hottest ticket in medical
      technology. But the infatuation with MRI was short-lived, and the promise of
      health care reform and strong utilization management have flattened utilization.
      So where does MRI fit in the new health care scene?

PMID- 7711784
TI  - VA hospitals. Phoning home.

PMID- 7711785
TI  - Innovators. The urban frontier.

PMID- 7711786
TI  - Suburbia. Health care 'R' us.

PMID- 7711787
TI  - Cost cutting. Keeping the fat off.

PMID- 7711788
TI  - Profile. James Sweeney, Coram Healthcare Corp., Denver. Interview by Katherine
      Morrall.

PMID- 7711789
TI  - Mergers. Lake Wobegone meets Minneapolis.

PMID- 7711790
TI  - Managing Medicaid. The monster called red tape.

PMID- 7711791
TI  - Partners in change are ready to roll.

PMID- 7711792
TI  - Ensuring accurate references.
AB  - About one-third of published nursing articles have some type of error in the
      references. Authors need to ensure that references are accurate before submitting
      the manuscript to the journal or book publisher. This author who has conducted
      research on reference errors and is an experienced author gives you practical
      steps to prevent errors in your manuscript.

PMID- 7711793
TI  - Tips on writing by interview.
AB  - Personal interviews add spice to publications--a well-written interview can
      inspire as well as inform. Here are 17 tips on writing by interview that will
      come in handy whether you are interviewing one person or several.

PMID- 7711794
TI  - Something borrowed, something new: how to tell the difference.
AB  - Plagiarism can be prevented. This article gives tips to nurses on preventing
      plagiarism problems in manuscripts they write or edit. The experienced author
      provides insight into the problem and suggests specific strategies for preventing
      the problem.

PMID- 7711795
TI  - Writing for the busy reader.
AB  - While the number of nursing journals has increased, the amount of time nurses
      have to read has decreased. This leaves nurse readers in a dilemma of when to
      find time to read their publications. Many nurses put their publications aside
      when they receive them, hoping to get more time later. Today, the author and
      editor need to develop writing styles which assist the busy nursing leader to
      read and comprehend quickly. This author provides ten tips on writing for the
      busy reader.

PMID- 7711796
TI  - Does a newsletter editor get co-authorship?

PMID- 7711798
TI  - Subliminal semantics.

PMID- 7711797
TI  - In good alignment.

PMID- 7711799
TI  - Searching for their roots in birth.

PMID- 7711800
TI  - No glove, no handshake.

PMID- 7711801
TI  - Birthing choices.

PMID- 7711802
TI  - Back to basics.

PMID- 7711803
TI  - Practice makes perfect.

PMID- 7711804
TI  - Charting fundamentals.

PMID- 7711806
TI  - Little Black Book pages for second stage.

PMID- 7711805
TI  - Under what circumstances should the midwife intervene.

PMID- 7711807
TI  - Renewing our faith in second stage.

PMID- 7711808
TI  - Return to trust.

PMID- 7711809
TI  - Serving our birthing sisters.

PMID- 7711810
TI  - Pacific rim memories.

PMID- 7711811
TI  - The medicalization of the second stage of labor.

PMID- 7711812
TI  - Memories of Heather.

PMID- 7711814
TI  - Medical information available.

PMID- 7711813
TI  - The journey-dance of labor and birth.

PMID- 7711815
TI  - Gallstones in pregnancy.

PMID- 7711816
TI  - Finger-feeding a preemie.

PMID- 7711817
TI  - Preventing feeding-associated aspiration.
AB  - Aspiration and its sequela aspiration pneumonia are frequent complications
      associated with enteral feeding. The purpose of this article is to provide a
      framework for recognizing aspiration events, identifying at-risk patients, and
      developing research-based strategies to prevent aspiration.

PMID- 7711818
TI  - Diabetic peripheral neuropathies.
AB  - Diabetic peripheral neuropathy is not just a pain in the leg, a symptom of one of
      many diabetic peripheral neuropathies. Rather, diabetic peripheral neuropathy
      causes many symptoms, and requires individualized medical and nursing management
      based on the type of neuropathy.

PMID- 7711819
TI  - Untied: a safe alternative to restraints.
AB  - Designing safe, appropriate, and nonmanpower-dependent alternatives to the
      physical restraint of confused and agitated patients is a significant nursing
      problem. An environmental intervention is proposed to reduce restraint use,
      improve patient outcomes, and use nursing resources more effectively.

PMID- 7711820
TI  - Effective mouth care for head and neck radiation therapy patients.
AB  - The American Cancer Society (1994) estimated that 42,100 people were diagnosed
      with head and neck cancers in 1994. The purpose of this article is to provide
      information regarding incidence and survival rates and to discuss risk factors
      and high-risk behaviors associated with head and neck cancer. The author reviews
      basic oral anatomy, radiobiology, and current research related to mouth care and
      symptom management. Innovative measures that can be used by both health care
      professionals and patients to reduce mouth problems caused by radiation therapy,
      and professional recommendations for mouth care are included.

PMID- 7711821
TI  - Monitoring vital signs to identify postoperative complications.
AB  - Vital signs are an important component in assessing patients' postoperative
      recovery. An evaluation study was conducted to determine the effects of changing
      the frequency of vital signs on recognizing complications. The results supported
      reducing the frequency of vital signs monitoring.

PMID- 7711822
TI  - Special nursing considerations for SLE patients.

PMID- 7711823
TI  - Cases of interest/regulatory update.

PMID- 7711824
TI  - Interferon beta for treatment of multiple sclerosis.

PMID- 7711825
TI  - Doing good: an ethical quandary.

PMID- 7711826
TI  - Redesigning documentation: clinical pathways, flowsheets, and variance notes.

PMID- 7711828
TI  - Entering the arena.

PMID- 7711827
TI  - Change in health care will and should affect student placement.

PMID- 7711829
TI  - Nursing implications for the adult patient receiving nutritional support.
AB  - Many patients receive nutritional support during their hospitalization. Nurses
      caring for these patients must be knowledgeable about the indications,
      appropriateness, and complications related to parenteral and enteral nutrition.

PMID- 7711830
TI  - Back and forth: the regulation and function of transbilayer phospholipid movement
      in eukaryotic cells.
AB  - That some membranes restrict certain lipid species to one side of the bilayer and
      others to the opposite side has been known for two decades. However, how this
      asymmetric transbilayer distribution is generated and controlled, how many and
      what type of membranes are so structured, and even the reason for its existence
      is just now beginning to be understood. It has been a decade since the discovery
      of an activity which transports in an ATP-dependent manner only the
      aminophospholipids from the outer to the inner leaflet of the plasma membrane.
      This aminophospholipid translocase has yet to be isolated, reconstituted, and
      identified molecularly. Elevating intracellular Ca2+ allows all the major classes
      of phospholipids to move freely across the bilayer, scrambling lipids and
      dissipating asymmetry. The nature of this pathway and its mode of activation by
      Ca2+ remain to be determined. Though loss of transbilayer asymmetry by blood
      cells clearly produces a procoagulant surface and increases interactions with the
      reticuloendothelial system, it remains to be elucidated whether maintenance of
      blood homeostasis is just one expression of a more general raison d'etre for
      lipid asymmetry. It is these persisting uncertainties and gaps in our knowledge
      which make the field such an interesting and exciting challenge at the present
      time.

PMID- 7711831
TI  - Glucose-6-phosphatase proteins of the endoplasmic reticulum.
AB  - Hepatic glucose-6-phosphatase (G-6-Pase) catalyses the terminal step of hepatic
      glucose production and it plays a key role in the maintenance of blood glucose
      homeostasis. Hepatic G-6-Pase is an integral resident endoplasmic reticulum (ER)
      protein and it is part of a multicomponent system. Its active site is situated
      inside the lumen of the ER and transport proteins are needed to allow its
      substrates, glucose-6-phosphate (G-6-P) (and pyrophosphate), and its products,
      phosphate and glucose to cross the ER membrane. In addition, a calcium-binding
      protein is also associated with the G-6-Pase enzyme. Recent immunological studies
      have shown that G-6-Pase (which has conventionally been thought to be present
      only in the gluconeogenic organs) is present in minor cell types in a variety of
      human tissues and that its distribution changes dramatically during human
      development. In all the tissues, enzymatic analysis, direct transport assays
      and/or immunological detection of the ER glucose and phosphate transport proteins
      have been used to demonstrate the presence and activity of the whole G-6-Pase
      system. The G-6-Pase protein is very hydrophobic and has proved difficult to
      purify to homogeneity. Four proteins of the system have now been isolated and
      polyclonal antibodies have been raised against them; two have also been cloned.
      The available sequences, together with topological studies, have given some
      information about both the topology of the proteins in the ER and the probable
      mechanisms by which the proteins are retained in the ER.

PMID- 7711832
TI  - Cloning, sequence analysis and expression pattern of mouse desmocollin 2 (DSC2),
      a cadherin-like adhesion molecule.
AB  - Desmocollins are cadherin-like adhesion molecules of desmosomes. We have
      determined the full cDNA sequence of a murine desmocollin, the homologue of human
      and bovine type 2 desmocollins (DSC2), and studied its tissue distribution and
      expression in stratified epithelia. An 8.5 day mouse embryo cDNA library was
      screened yielding overlapping clones which encoded the mouse DSC2. This gene has
      an open reading frame of 2710 base pairs (bp) encoding a polypeptide of 902 amino
      acids (aa). The polypeptide comprises a signal peptide, a precursor peptide, and
      a mature protein of 766 aa having an extracellular domain of 549 aa, a single
      transmembrane domain and a cytoplasmic domain of 184 aa. Like other desmocollins,
      murine DSC2 has two products, Dsc2a and Dsc2b, produced by alternative splicing
      of a 46 bp exon which encodes 11 COOH-terminal aa followed by an in-frame stop
      codon. Inclusion of this exon forms Dsc2b which is 54 aa shorter than Dsc2a.
      Mouse Dsc2a shows 75.7% amino acid identity to human and 63.3% identity to bovine
      Dsc2a. The mouse desmocollin is also homologous to the cadherins; 32.2% to the
      most closely related typical cadherin, human N-cadherin. DSC2 is ubiquitously
      expressed in epithelial tissues and the heart of adult mice and from the
      blastocyst stage of development. In situ hybridization shows that the gene is
      most strongly expressed suprabasally in stratified epithelia, similar to the
      expression of bovine DSC2.

PMID- 7711833
TI  - Na,K-ATPase characterized in artificial membranes. 1. Predominant conformations
      and ion-fluxes associated with active and inhibited states.
AB  - The Na,K-ATPase (NKA) system is the receptor for the cardioactive steroids of
      plant or animal origin. It is not yet known whether passive ion fluxes traverse
      the inactivated receptor and thereby contribute to the hormonal, pharmacological
      or toxic actions of these compounds. To look for putative passive ion-fluxes
      across the ouabain-NKA complex, we incorporated it into the artificial membrane
      of liposomes. Since this synthetic membrane is virtually impermeable to Na and K
      ions, the hypothetical ion-fluxes mediated by the NKA can be determined. E2-forms
      and E2-ouabain-forms of purified NKA were incorporated, in parallel, into
      separate liposome preparations and the permeability of the resulting E2-liposomes
      and E2-ouabain-liposomes to K, Na and Ca ions was compared. The E2-liposomes
      expressed a typical K-permeability which was not observed in the E2-ouabain
      liposomes; the latter showed a slightly higher Na-permeability and a similar Ca
      permeability as compared to the former. Thus, ouabain does not induce leaks for K
      or Ca ions in the NKA molecule.

PMID- 7711834
TI  - Na,K-ATPase characterized in artificial membranes. 2. Successive measurement of
      ATP-driven Rb-accumulation, ouabain-blocked Rb-flux and palytoxin-induced Rb
      efflux.
AB  - The Na,K-ATPase is a multifunctional system anchored in the membrane of
      eukaryotic cells; it is responsible for the establishment and regulation of the
      Na/K balance of cell and organism by a stoichiometric mechanism linking Na
      extrusion to K uptake and ATP hydrolysis. The receptor for cardioactive steroids
      such as digoxin and ouabain is located at the extracellular surface of the
      system. Conversely, palytoxin, the most potent animal toxin, exerts its toxic
      effect by creating nonspecific leaks in the cell membrane leading to K-efflux and
      influx of Na and Ca ions. Ouabain prevents the pore-forming action of palytoxin
      in cells and therefore Na,K-ATPase is suspected to be the common receptor of
      ouabain and palytoxin. We have developed an artificial membrane system to
      determine structure-function relationships and ligand interactions of purified
      Na,K-ATPase: two-sided, bi-directional ATP-filled liposomes. In this system, ATP
      driven 86Rb accumulation, arrest of 86Rb-uptake by ouabain, and palytoxin-induced
      86Rb-leak were measured successively in the same preparation. Ouabain prevented
      the leak when the enzyme was ouabain-sensitive (rabbit kidney) but not when it
      was ouabain-resistant (rat kidney). On the basis of these data in conjunction
      with conformational analyses, allosteric conformational competition for the
      ouabain-palytoxin antagonism is proposed.

PMID- 7711835
TI  - Subcellular distribution and immunocytochemical localization of Na,K-ATPase
      subunit isoforms in human skeletal muscle.
AB  - The expression of Na,K-ATPase isoforms was investigated in human skeletal muscle
      membranes isolated by subcellular fractionation. The alpha 1, alpha 2, alpha 3
      and beta 1 subunits were detectable in membranes prepared from the human soleus
      muscle. The alpha 1 subunit was largely detected in a fraction enriched with
      plasma membranes (PM), its abundance in an intracellular membrane fraction (IM)
      accounted for only 4% of that in the PM fraction. No alpha 1 subunits were
      detected in membranes of sarcoplasmic reticulum (SR) origin. The PM and IM
      fractions were enriched with alpha 2 subunits which were less abundant in the SR
      enriched fraction. The abundance of alpha 2 molecules within the IM fraction was
      about 75% of that in the PM fraction when the total protein content for the two
      fractions was taken into account. Immunocytochemical studies confirmed the
      localization of the alpha 1 subunit to the muscle cell surface. The alpha 2
      subunit was also found to be present in the cell surface but the observation that
      alpha 2 immunofluorescence was diffusely dispersed throughout the muscle fibre
      indicated that it was also present intracellularly, consistent with its
      biochemical localization in the PM and IM membrane fractions. The alpha 3 subunit
      was detected largely in the PM fraction but the lack of good antibodies to this
      isoform precluded an analysis of its immunocytochemical localization. The beta 1
      subunit was enriched in the PM fraction but was also detected to a modest extent
      in the IM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711836
TI  - Conformation of the cytoplasmic domain of phospholamban by NMR and CD.
AB  - Nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy have
      been used to characterize the conformation of the putative cytoplasmic domain of
      phospholamban (PLB), an oligomeric membrane-bound protein which regulates the
      activity of the cardiac sarcoplasmic reticulum Ca(2+)-dependent ATPase. In
      aqueous solution the 25-residue peptide adopts a number of rapidly
      interconverting conformers with no secondary structural type obviously
      predominating. However, in trifluoroethanol (TFE) the conformation, while still
      highly dynamic, is characterized by a high proportion of helical structures.
      Evidence for this is provided by alpha CH chemical shifts and low NH chemical
      shift temperature coefficients, small NH-alpha CH intraresidue scalar coupling
      constants, a substantial number of distinctive interresidue nuclear Overhauser
      effects (NOEs) [dNN(i, i + 1), d alpha N(i, i + 3), d alpha beta(i, i + 3) and d
      alpha N(i, i + 4)] and characteristic CD bands at 190 (positive), 206 (negative)
      and 222 nm (negative). The helicity is interrupted around Pro-21. The activity of
      PLB is regulated by phosphorylation at either Ser-16 or Thr-17. CD shows that
      phosphorylation at Ser-16 by the cAMP-activated protein kinase causes about an
      11% decrease in alpha-helical content in TFE.

PMID- 7711837
TI  - Structure and function of the class C tetracycline/H+ antiporter: three
      independent groups of phenotypes are conferred by TetA (C).
AB  - The class C tetracycline/H+ antiporter, TetA(C), confers nine distinct phenotypes
      in Escherichia coli: resistance to tetracycline, reduced culture density at
      stationary phase (growth yield), increased supercoiling of plasmid DNA, delayed
      growth in succinate minimal medium, complementation of potassium uptake defects,
      increased susceptibility to cadmium, increased susceptibility to fusaric acid,
      increased susceptibility to bleomycin and increased susceptibility to several
      classes of cationic aminoglycoside antibiotics. These nine phenotypes were
      resolved into three 'linkage' groups based on their patterns of suppression by
      mutations of the tetA(C) gene of plasmid pBR322. Group I includes resistance to
      tetracycline, increased susceptibility to cadmium and reduced growth yield. Group
      II includes delayed growth in succinate minimal medium and complementation of
      potassium uptake defects. Group III includes increased supercoiling of plasmid
      DNA and increased susceptibilities to fusaric acid, bleomycin and cationic
      aminoglycosides. Phenotypes of Groups II and III, but not Group I, also were
      conferred by a chimeric gene encoding a fusion between the N-terminal 34 residues
      of TetA(C) and the C-terminal 429 residues of a structurally-similar protein, the
      E. coli galactose/H+ symporter, GalP. In contrast, none of these phenotypes was
      conferred by a chimeric gene encoding a fusion between the N-terminal 34 residues
      of TetA(C) and a structurally-dissimilar protein, TEM beta-lactamase. These
      results demonstrate that the three groups of linked phenotypes are dependent on
      different elements of the TetA(C) amino acid sequence, implying that TetA(C)
      confers these phenotypes by at least three independent mechanisms.

PMID- 7711838
TI  - Overview of fluorophores.

PMID- 7711839
TI  - Direct immunofluorescent labeling of cells.

PMID- 7711840
TI  - Fluorescence labeling of surface antigens of attached or suspended tissue-culture
      cells.

PMID- 7711841
TI  - Purification of antibodies using ammonium sulfate fractionation or gel
      filtration.

PMID- 7711842
TI  - Fluorescence labeling of intracellular antigens of attached or suspended tissue
      culture cells.

PMID- 7711843
TI  - Fluorescent labeling of surface or intracellular antigens in whole-mounts.

PMID- 7711844
TI  - Overview of antigen detection through enzymatic activity.

PMID- 7711845
TI  - The peroxidase-antiperoxidase (PAP) method.

PMID- 7711846
TI  - The avidin-biotin complex (ABC) method.

PMID- 7711847
TI  - Labeled avidin binding (LAB) method.

PMID- 7711848
TI  - ELISA on attachment-dependent or suspension grown cells.

PMID- 7711849
TI  - Use of immunogold with silver enhancement.

PMID- 7711850
TI  - Tissue disaggregation.

PMID- 7711851
TI  - Indirect immunofluorescent labeling of viable cells.

PMID- 7711852
TI  - Purification of antibodies using ion-exchange chromatography.

PMID- 7711853
TI  - Deparaffinization and processing of pathologic material.

PMID- 7711854
TI  - Assay for phagocytosis.

PMID- 7711855
TI  - Assay for filamentous actin.

PMID- 7711856
TI  - Assay for chemoattractant binding.

PMID- 7711857
TI  - Assay for oxidative metabolism.

PMID- 7711858
TI  - Purification of antibodies using affinity chromatography.

PMID- 7711859
TI  - Fixation and embedding.

PMID- 7711860
TI  - Preparation of colloidal gold.

PMID- 7711861
TI  - Overview of antibody use in immunocytochemistry.

PMID- 7711862
TI  - Conjugation of colloidal gold to proteins.

PMID- 7711863
TI  - Colloidal gold/streptavidin methods.

PMID- 7711864
TI  - Overview of fluorescence analysis with the confocal microscope.

PMID- 7711865
TI  - Overview of laser microbeam applications as related to antibody targeting.

PMID- 7711866
TI  - Nucleic acid immunocytochemistry. In situ hybridization to human chromosomes of
      an alkaline phosphatase-labeled centromeric probe.

PMID- 7711867
TI  - Purification of antibodies using protein A-Sepharose and FPLC.

PMID- 7711868
TI  - Fluorescence in situ hybridization using whole chromosome library probes.

PMID- 7711869
TI  - Overview of immunocytochemical approaches to the differential diagnosis of
      tumors. Diagnostic applications in the clinical laboratory.

PMID- 7711870
TI  - Biotinylation of antibodies.

PMID- 7711871
TI  - Overview of cell fixation and permeabilization.

PMID- 7711872
TI  - Beta 3-adrenoceptor: an update.

PMID- 7711873
TI  - Interleukin-6 and the thyroid.

PMID- 7711874
TI  - The Na+/I- cotransporter: a thyroid autoantigen?

PMID- 7711875
TI  - Identification of the thyroid Na+/I- cotransporter as a potential autoantigen in
      thyroid autoimmune disease.
AB  - The thyroid gland is the target of several autoimmune diseases. Specific thyroid
      proteins have been identified as autoantigens associated with these diseases
      (e.g. thyroperoxidase, thyroglobulin and the thyrotrophin (TSH) receptor). In
      this paper, we report that the serum of a patient suffering from Hashimoto's
      thyroiditis, autoimmune gastritis and rheumatoid arthritis was able to inhibit
      the chronic TSH-induced I- uptake of dog thyrocytes in culture, even at a 1:1000
      fold dilution, without affecting their 86Rb+ uptake. This blocking activity is
      rare as 147 sera (from patients positive for antibodies to the thyroid microsomes
      and the gastric parietal cell antigen, patients with Sjogren's syndrome, patients
      with a high titre of microsomal antibodies and low or negative for antibodies to
      thyroperoxidase, and patients with a high titre of microsomal antibodies and
      frank hypothyroidism) were negative when tested for their ability to inhibit I-
      uptake. Subsequently we tested 20 murine monoclonal antibodies previously
      obtained by immunizing mice with a crude human thyroid membrane preparation,
      which were all negative when tested against thyroglobulin and thyroperoxidase.
      One of the monoclonal antibodies displayed a 50% inhibition of the chronic TSH
      induced 125I- uptake of dog thyrocytes without affecting the 86Rb+ uptake of the
      cells. Immunoglobulins purified from the ascite fluid by affinity chromatography
      on a protein A cellulose column had the same characteristics. Taken together, the
      data suggest that thyroidal 125I- uptake can be inhibited by antibodies, that
      autoantibodies in the patient's serum are most probably responsible for the
      observed inhibition and therefore that the Na+/I- cotransporter is probably an
      autoantigen.

PMID- 7711876
TI  - Retrospective evaluation of subtotal and total thyroidectomy in Graves' disease
      with and without endocrine ophthalmopathy.
AB  - A retrospective analysis was performed in 173 consecutive patients with Graves'
      disease (GD) with the principal aim of evaluating the influences of subtotal (N =
      157) and total (N = 19) thyroidectomy on postoperative recurrence rates,
      endocrine ophthalmopathy (EO) and thyrotropin receptor antibody (TSH-R-ab)
      titres. Postoperatively recurrent disease, identified by increased thyroid
      hormone levels, occurred in 32 patients (20%) who underwent subtotal resection.
      These recurrences were associated with over-representation of preoperative EO (p
      < 0.001) as well as high TSH-R-ab levels postoperatively (p < 0.05-0.01).
      Subtotal and total resections were followed by an aggravation of preoperative EO
      in nine (16%) and one (6%), and by a development of EO in two and none of the
      patients, respectively. Persistently elevated TSH-R-ab titers during thyrostatic
      therapy became close to normalized in seven (32%) and 15 (88%) of the patients
      undergoing subtotal or total thyroidectomies, respectively, which illustrates a
      thyroid tissue dependency of the autoantibody production. Among the total
      material of 173 patients, altogether 75 cases exhibited persistent or progressive
      EO and/or TSH-R-ab elevation after more than 1 year of preoperative thyrostatic
      treatment. In this group, recurrent GD or aggravated EO occurred in 23 (39%) of
      those operated with subtotal resection and in one (6%) of those undergoing total
      thyroidectomy (p < 0.05). The results thus indicate that EO, particularly at the
      time of surgery, and prevailing TSH-R-ab titers are associated with an increased
      risk of recurrent GD and suggest that patients exhibiting these characteristics
      should benefit from total rather than subtotal thyroidectomy.

PMID- 7711877
TI  - Kinetic analysis of thyroid hormone action on glucose metabolism in man.
AB  - Thyroid hormone action on insulin's effect on glucose kinetics was investigated
      with the use of a physiological three compartment model. In six healthy
      volunteers before and after 14 days of thyroxine treatment (300 micrograms/day),
      a bolus of [3-H3]glucose was injected and the time course of plasma radioactivity
      was followed closely for 150 min. Then a hyperinsulinemic (1 mU.min-1.kg-1) and
      euglycemic clamp was started, and euglycemia was maintained for another 250 min.
      A second bolus of the tracer was then given at 240 min, and the plasma
      radioactivity was followed for 160 min. Insulin stimulated basal plasma glucose
      clearance fourfold (p < 0.001) and completely suppressed basal hepatic glucose
      production (p < 0.001). Concomitantly, the total distribution volume of glucose
      was increased by 19% (p < 0.05); this change was accompanied by about 50%
      expansion of the slowly exchanging glucose pool (putatively representing the
      insulin-dependent compartment). Thyroxine treatment increased plasma
      triiodothyronine by about 20% (0.1 > p > 0.05) but did not affect basal glucose
      turnover, insulin-stimulated plasma glucose clearance or the insulin-induced
      suppression of endogenous glucose output. However, thyroxine treatment blunted
      the insulin-induced increases in total distribution volume and the slowly
      exchanging pool of glucose (p = NS vs the basal state). We conclude that minor
      changes in plasma triiodothyronine (such as occur during overfeeding) do not
      interfere with the ability of insulin to stimulate the rate of disappearance of
      glucose or suppress endogenous glucose release; however, our data suggest that
      they induce finer changes in glucose kinetics, possibly reflecting acceleration
      or intracellular glucose degradation.

PMID- 7711878
TI  - Diagnostic puzzle of the adrenal "incidentaloma".

PMID- 7711879
TI  - Abnormalities of endocrine function in patients with clinically "silent" adrenal
      masses.
AB  - Because, in recent years, patients with incidentally discovered adrenal masses
      have been encountered increasingly, their endocrine function was investigated in
      basal conditions and after dynamic tests. Thirty-two patients (23 women and 9
      men, aged 28-74 years) were studied. Lesion diameter, as documented by computed
      tomography and/or nuclear magnetic resonance imaging, ranged between 5 and 65 mm;
      the tumors were localized on the right in 22 patients, on the left in 5 and
      bilaterally in 5 cases. In basal conditions, urinary free cortisol (UFC)
      excretion, plasma adrenocorticotropin (ACTH) and cortisol levels were normal,
      except for 4 patients who showed high UFC and ACTH levels in the low-normal
      range. Ovine corticotropin-releasing hormone (CRH, 1 microgram/kg iv) was given
      to 18 patients, inducing normal ACTH and cortisol responses in 12, blunted
      responses in 4 and no response in 2 cases. No reduction in ACTH and cortisol
      levels after suppression tests was observed in 4 of 29 patients after
      dexamethasone (1 mg overnight) or in 6 of 29 after loperamide. The 4 patients who
      were unresponsive to both tests did not show any further inhibition after high
      dose dexamethasone administration, had low plasma ACTH levels and showed impaired
      or absent responses to the CRH test: they were diagnosed as affected with
      preclinical Cushing's syndrome. An exogenous ACTH test performed in 30 patients
      caused a normal cortisol rise. Basal mean 17-hydroxy-progesterone (17-OHP) levels
      were not different from those in normal subjects.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7711880
TI  - Four years' treatment of resistant acromegaly with octreotide.
AB  - This study was designed to ascertain the long-term safety and efficacy profile of
      the somatostatin analogue octreotide as treatment of refractory acromegaly. Eight
      patients (aged 21-62 years) with persistent growth hormone (GH) elevation
      (duration 1-15 years) despite previous therapy were studied. Octreotide was given
      subcutaneously in increasing doses for the first year to a maximum of 500
      micrograms three times daily. The dose then was reduced to 200 micrograms three
      times daily for the next 3 years. At annual assessments, 24-h GH profiles,
      insulin-like growth factor I (IGF-I) and a side-effect profile including gall
      bladder ultrasound were studied. Oral glucose tolerance tests (75 g) were
      performed basally and after 6 months and 3 years of therapy. Haemoglobin A1
      (HbA1) was also assessed. Side effects were recorded. Mean GH (+/- SEM) was 36.0
      +/- 9 mU/l basally and was reduced significantly at all subsequent assessments on
      therapy (4-year mean, 9.4 +/- 2.1 mU/l). The IGF-I level also remained suppressed
      and was normalized in four of eight patients who remained on octreotide. Fasting
      plasma glucose and HbA1 were not changed by therapy but 2-h glucose was elevated
      after 6 months and 3 years (basal mean, 7.6 mmol/l (5.3-9.0 mmol/l); 3-year mean,
      10.7 mmol/l (8.4-15.7 mmol/l); p < 0.05). Five patients developed gallstones and
      in three these had disappeared following 1 year of bile salt dissolution therapy.
      Octreotide continues to suppress serum GH and IGF-I long term without attenuation
      of effect. Gallstone formation is a major side effect.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7711881
TI  - Midmolecular parathyroid hormone-related peptide in serum during pregnancy,
      lactation and in umbilical cord blood.
AB  - Indications of an important physiological role of parathyroid hormone-related
      peptide (PTHrP) for fetal calcium homeostasis, maternal-fetal calcium transport
      and reproduction have accumulated over recent years. The PTHrP concentrations
      were measured by an earlier developed midregion radio-immunoassay in serum from
      lactating healthy females and umbilical cord blood and compared with levels in
      age-matched non-pregnant or lactating females. The PTHrP concentrations could be
      measured in all samples after silica cartridge C18 extraction of 10-12 ml of
      serum. The concentrations were significantly higher during lactation (mean +/-
      SD: 0.72 +/- 0.14 pmol/l, N = 22) and in umbilical cord blood (0.85 +/- 0.18
      pmol/l, N = 12) compared with healthy age-matched women (0.48 +/- 0.09 pmol/l, N
      = 10, p < 0.001). The molecular forms of PTHrP were also studied in an age
      matched control group, in pregnant women and in umbilical cord blood by gel
      chromatography in a fast protein liquid chromatography system of Sep-Pak
      extracted pooled serum. In all three groups we found heterogeneity of the
      molecular forms with two predominant peaks. The smallest fragment had a molecular
      weight of 4-6 kD while the largest form appeared as a high-molecular-weight
      molecule. In conclusion, the concentrations of midmolecule PTHrP fragments in
      serum are elevated during lactation and in umbilical cord blood. Because the
      midregion of PTHrP has unique actions, our results indicate that PTHrP may play
      an important physiological role for the mother and for the maternal-fetal calcium
      transport.

PMID- 7711882
TI  - Inappropriately low levels of gonadotrophins in amenorrhoeic women with alcoholic
      and non-alcoholic cirrhosis.
AB  - We investigated a group of 111 amenorrhoeic females with associated liver
      disease. These comprised alcoholic cirrhotics (N = 38), non-alcoholic cirrhotics
      (N = 12), non-cirrhotic alcoholics (N = 21) and those suffering from other
      chronic liver diseases (N = 40) admitted to our medical department from 1986 to
      1991. The serum levels of luteinizing hormone (LH) and follicle-stimulating
      hormone (FSH), oestradiol, testosterone, sex hormone binding globulin (SHBG) and
      prolactin were measured. Serum LH was decreased below the normal range in 50% of
      patients with alcoholic cirrhosis and in 42% of patients with non-alcoholic
      cirrhosis. One third of non-cirrhotic alcoholics also had decreased LH, in
      contrast to only 8% of patients with other chronic liver diseases (p < 0.01). A
      close correlation was found between LH and FSH when all patients were pooled (r =
      0.91, p < 0.001). A gonadotrophin-releasing hormone (GnRH) injection elicited a
      clear LH and FSH response in 11 out of 14 patients with cirrhosis, indicating
      that the hypothalamus rather than the pituitary is the site of disturbance in
      gonadotrophin secretion. Serum SHBG was within normal limits and similar in all
      four groups. In nine females with alcoholic cirrhosis who abstained for 3 months,
      serum SHBG increased significantly from 39 +/- 18 to 70 +/- 25 nmol/l (p <
      0.001), while LH increased in five of nine females and was unchanged in four. In
      conclusion, half of the amenorrhoeic females with alcoholic as well as non
      alcoholic cirrhosis had inappropriately low serum LH and FSH levels, indicating
      dysfunction of the hypothalamo-pituitary axis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711883
TI  - Altered glycosylation of pituitary gonadotropins in anorexia nervosa: an
      alternative explanation for amenorrhea.
AB  - To investigate the relevance of glycoprotein polymorphism to gonadotropin
      bioactivity in vivo, plasma follicle-stimulating hormone (FSH) and luteinizing
      hormone (LH), 17 beta-estradiol (E2), testosterone and sex hormone binding
      globulin (SHBG) levels in 17 amenorrheic women affected with anorexia nervosa (14
      29 years) and 10 age-matched normally cycling women were evaluated. Plasma FSH
      and LH levels were assayed using radioimmunoassay (RIA) and immunoradiometric
      assay (IRMA) methods, before and after concanavalin A-Sepharose (Con A) affinity
      chromatography. Significant RIA-IRMA differences in FSH and LH plasma values were
      present only in women with anorexia nervosa (p < 0.005). Moreover, in these
      patients both FSH and LH showed a reduced binding to the Con A, expressed as a
      percentage of unbound, suggesting altered glycosylation of these moieties. In
      conclusion, these findings hypothesize the involvement of glycosylation
      polymorphism in RIA-IRMA differences; support the usefulness of both RIA and IRMA
      methods in FSH and LH evaluation, before and after Con A chromatography; and
      suggest a new pathogenetic pathway to explain amenorrhea in anorexia nervosa.

PMID- 7711884
TI  - Water retention after oral chlorpropamide is associated with an increase in renal
      papillary arginine vasopressin receptors.
AB  - Chlorpropamide (CP), a sulfonylurea used for treatment of non-insulin dependent
      diabetes mellitus, is known to potentiate the antidiuretic action of arginine
      vasopressin (AVP), predisposing to hyponatremia. It has been suggested that CP
      acts directly on the antidiuretic vasopressin receptor. Detailed studies on the
      influence of CP on the AVP receptor, however, have been hampered by lack of a
      suitable radioligand. Using a newly developed radioiodinated derivative of AVP
      with high specific activity and high affinity for the AVP V2-receptor (125I-[8-(p
      (OH)-phenylpropionyl)]-LVP), we studied the role of AVP V2-receptors in CP
      induced water retention. Male-Sprague-Dawley rats were treated orally with 40 mg
      CP/day or placebo for 7 days, after which Scatchard analysis was performed using
      membranes prepared from homogenized renal papilla. After oral water load, CP
      treated rats but not control rats showed a significant decrease in plasma
      osmolality (289 +/- 2.2 to 284 +/- 0.8 mosmol/kg, p < 0.05). The Kd was 0.69 +/-
      0.16 nmol/l in controls and 0.70 +/- 0.12 nmol/l after CP treatment (NS); Bmax
      was 129 +/- 5.3 nmol/kg protein in controls (N = 8). Chlorpropamide significantly
      increased receptor density (Bmax) to 167 +/- 8.4 nmol/kg protein (N = 8) (p <
      0.05). Plasma AVP did not change significantly during CP treatment. These data
      show for the first time that CP in vivo increases the density of AVP V2 receptors
      without altering plasma AVP. This is associated with an impairment in water
      excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711885
TI  - Identification and quantification of human kidney atrial natriuretic peptide
      receptors.
AB  - The present study determined 125I-label atrial natriuretic peptide (ANP) binding
      sites in human kidney glomerular and papillary membranes. The membranes were
      prepared from non-malignant renal tissue obtained at nephrectomy of patients with
      renal carcinoma. To evaluate the proportion of ANP receptor classes ANP-R1 (ANPR
      A, -B) versus ANP-R2 (ANPR-C), competitive binding studies were performed using
      [125I]-ANP in the presence of increasing concentrations of ANP or an internally
      ring-deleted analog, des(Gln116, Ser117, Gly118, Leu119, Gly120)ANP(102-121),
      called C-ANP, which binds selectively to ANPR-C receptors. Analysis of the
      competitive binding curve with ANP in glomerular membranes suggested the presence
      of one group of high-affinity receptors with dissociation constant Kd = 26 +/- 12
      pmol/l and density Bmax = 101 +/- 47 nmol/kg protein. A decrease of 10-30% in
      Bmax with no change in Kd was obtained in the presence of excess (10(-6) mol/l) C
      ANP, suggesting the existence of a small amount of a second class of receptors,
      the ANPR-C class. The densities of ANPR-A, -B versus ANPR-C receptors in human
      glomeruli, calculated from competitive inhibition experiments, were 75 +/- 42 and
      22 +/- 16 nmol/kg protein (N = 8). Autoradiography of the sodium dodecyl sulfate
      polyacrylamide gel electrophoresis under reducing conditions showed two bands: a
      highly labeled 130kD band and a weakly labeled 66 kD band, both displaced by ANP.
      Only the 66-kD band was displaced by the C-ANP analog. Human papilla membrane, as
      shown by competition binding studies and SDS gel electrophoresis, presented only
      one class of receptors with Kd = 40 +/- 23 pmol/l (mean +/- SD, N = 3) and Bmax =
      17 +/- 6.3 nmol/kg protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711886
TI  - Biphasic effect of interleukin-1 beta on arginine vasopressin-induced cellular
      cyclic adenosine monophosphate production in cultured rat renal papillary
      collecting tubule cells.
AB  - The present study was undertaken to determine whether interleukin (IL)-1 beta
      affects the response of cellular cyclic adenosine monophosphate production to
      arginine vasopressin (AVP) in cultured rat renal papillary collecting tubule
      cells. Arginine vasopressin increased cellular cAMP production in a dose
      dependent manner. A 10-min exposure of cells to IL-1 beta at a concentration of 1
      x 10(-12) mol/l or higher significantly reduced the AVP-induced increases in
      cellular cAMP production but did not affect the 2 x 10(-8) mol/l forskolin
      induced increases in cellular cAMP production. The IL-1 beta inhibition
      disappeared totally when cells were pretreated with 100 micrograms/l pertussis
      toxin for 2 h. In contrast, more than a 30-min exposure of cells to IL-1 beta
      increased basal cAMP levels and enhanced both the AVP-and forskolin-induced
      increases in cellular cAMP production. These results indicate that IL-1 beta
      produces biphasic regulation of AVP-induced cellular cAMP production in renal
      papillary collecting tubule cells. The inhibition by IL-1 beta is dependent on
      the activation of pertussis toxin-sensitive G protein. However, the mechanism
      whereby the longer exposure to IL-1 beta enhances cAMP production remains to be
      determined.

PMID- 7711887
TI  - Chronic stress and pituitary-adrenocortical responses to corticotropin-releasing
      hormone and vasopressin in female pigs.
AB  - Effects of long-term tethered housing (a condition of chronic stress) on
      pituitary-adrenocortical responsiveness to exogenous corticotropin-releasing
      hormone (CRH) and lysine8-vasopressin (LVP) were investigated in female pigs.
      Intravenous administration of CRH (dose range 10-440 pmol/kg body wt) or LVP (10
      880 pmol/kg body wt) elicited transient and dose-related increases in plasma
      concentrations of adrenocorticotropic hormone (ACTH) and cortisol. Comparison of
      the responses induced by the peptides indicated that CRH is a more potent ACTH
      secretagogue than LVP. Treatment with LVP produced a fivefold greater plasma
      cortisol/ACTH ratio than treatment with CRH, suggesting that in addition to
      stimulating pituitary ACTH release it enhanced the ability of the adrenal cortex
      to secrete cortisol in response to ACTH. Whereas concomitant administration of 10
      pmol CRH/kg body wt and 20 pmol LVP/kg body wt revealed an additive effect on
      ACTH release, synergism between both peptides was found with respect to their
      cortisol-releasing effect. Ten to thirteen weeks of chronic stress did not alter
      significantly the absolute ACTH and cortisol responses to the two peptides. In
      tethered pigs, the cortisol/ACTH ratio after CRH treatment, calculated from the
      area under the curve, was twofold that in loose-housed pigs. From these
      observations we conclude that after chronic stress the sensitivity of the
      adrenocortex to circulating ACTH was increased, whereas the sensitivity of the
      pituitary to CRH and/or LVP remained unaltered.

PMID- 7711888
TI  - Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice
      expressing human islet amyloid polypeptide/amylin.
AB  - To investigate the relationship between human islet amyloid polypeptide
      (IAPP)/amylin expression and islet amyloid deposits in the pathogenesis of human
      non-insulin-dependent diabetes mellitus (NIDDM), we developed transgenic mice
      using a human IAPP cDNA connected to an insulin promoter. Ribonucleic acid
      blotting and immunohistochemistry revealed the expression of the transgene in the
      pancreatic beta cells. Immunogold electron microscopy showed that beta-secretory
      granules contained the human C-terminal flanking peptide of the IAPP precursor.
      Reverse-phase HPLC demonstrated human and mouse IAPP amide in the pancreas.
      Electron microscopy showed the accumulation of fibril-like material in a
      considerable number of beta-secretory granules. These results suggest that in
      transgenic mice, the human IAPP precursor is expressed in beta cells and becomes
      normally sorted into beta-secretory granules in which normal conversion to mature
      human IAPP takes place. The human IAPP molecules, because of their
      amyloidogenesis, aggregate into amyloid fibrils in secretory granules. Glucose
      tolerance was normal at 7 months old and islet amyloid was not observed. A longer
      time may be required for islet amyloid deposits and hyperglycemia to develop in
      mice. Our working hypothesis is that in human NIDDM, IAPP aggregates into amyloid
      fibrils in beta-secretory granules, and that the fibrils are released into the
      extracellular space and islet amyloid deposits become substantial with time.

PMID- 7711889
TI  - Growth hormone (GH) modulates insulin-like growth factor I (IGF-I) and type I IGF
      receptor mRNA levels in the ovary of prepubertal GH-deficient rats.
AB  - In order to explore the potential role of growth hormone (GH) in modulating
      insulin-like growth factor I (IGF-I) gene expression in the prepubertal rat
      ovary, female rats were rendered GH deficient by neonatal administration of
      monosodium glutamate (MSG). One group of rats received vehicle and served as the
      control. At 21 days of age, MSG-treated rats received either GH or vehicle for 2
      weeks. On days 21, 24, 28 and 31 animals were weighed and subsets were sacrificed
      for liver RNA extraction. The remaining animals were sacrificed at day 35 when
      livers and ovaries were collected, and serum was obtained for GH determinations.
      The IGF-I mRNA levels were estimated by Northern blots and corroborated further
      by slot-blot analysis. The MSG-treated rats had lower body weights (p < 0.01) and
      GH levels (p < 0.05) than controls. Growth hormone replacement significantly
      accelerated the weight gain of MSG-treated rats. At day 24 and thereafter, three
      RNA IGF-I species (7.5, 1.8 and 0.8-1.2 kB) were seen in the liver. In the ovary,
      at age 35 days, two major IGF-I mRNA species (7.5 and 0.8-1.2 kb) were seen. The
      MSG treatment consistently reduced the levels of both IGF-I mRNA species in the
      ovary. Growth hormone administration partially restored their expression, both in
      the liver and in the ovary. In addition, ovarian type IIGF receptor mRNA levels
      were increased in the MSG-treated rats when compared to controls. This trend was
      reversed by GH replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711890
TI  - Pituitary-ovarian dysfunction in rats with induced nephrotic syndrome.
AB  - The reproductive hormonal profile was evaluated in female rats with experimental
      nephrotic syndrome induced with a single subcutaneous dose of puromycin
      aminonucleoside (PAN). Serum concentrations of luteinizing hormone (LH), follicle
      stimulating hormone (FSH), progesterone (P4), testosterone and 17 beta-estradiol
      (E2) were determined sequentially in control and experimental groups on days 1,
      3, 7 and 10 after PAN administration. Prolactin levels were also assessed on day
      10. In both groups, vaginal smears were taken daily throughout the study to
      evaluate cyclic histological changes. At the end of the experiment the
      histological appearance of the ovaries was evaluated by light microscopy.
      Nephrotic rats had a rapid loss of the estrous cycle starting on day 4, which set
      them at diestrus. At the same time the hormonal evaluation indicated a gradual
      decrease in E2, LH and P4 concentrations, starting from days 3, 7 and 10,
      respectively. No significant changes were noted in FSH or testosterone values.
      Besides, on day 10, prolactin concentrations remained unmodified. Even though
      most hormonal levels were found low on day 10, all values except E2
      (undetectable) corresponded to the interval reported for the diestrus phase.
      Likewise, histological examination of ovarian tissue from nephrotic rats showed a
      considerable increase in the number of atretic follicles. These findings indicate
      that female rats with nephrotic syndrome develop an important endocrine
      dysfunction that probably involves steroidogenic tissues (ovary and/or adrenal
      gland), and suggest the existence of a hypothalamic-hypophyseal impairment.

PMID- 7711891
TI  - Relaxin triggers calcium transients in human granulosa-lutein cells.
AB  - Although the peptide hormone relaxin is synthesized by the human corpus luteum in
      vivo, its potential to serve as a local factor in the regulation of luteal
      function is not clear. Using an enzyme-linked immunosorbent assay for human
      relaxin, we detected relaxin in the culture medium of human granulosa-lutein
      cells as early as after 6 days in culture. Moreover, 1 x 10(5) IU/l human
      chorionic gonadotropin stimulated relaxin release about fourfold during a 48-h
      incubation on culture days 6-8 (and 7-9), but not earlier (on days 1, 3 and 4).
      The stimulatory action of human chorionic gonadotropin on progesterone release
      was not influenced by relaxin, and relaxin alone was without stimulatory effect.
      However, human recombinant relaxin (between 0.1 and 12.5 micrograms/l) increased
      intracellular free Ca2+ basal levels to maximal peak levels exceeding 1000 nmol/l
      in about 64% of all tested cells (N = 168) with no obvious dependency on the
      culture day. The relaxin-induced Ca2+ signal was not affected by removal of
      extracellular Ca2+. As depletion of intracellular Ca2+ stores by ionomycin
      rendered the cells unresponsive to relaxin or diminished their ability to
      respond, these results point to an intracellular source of the Ca2+ signal. In
      summary, our data indicate the presence of a functional relaxin receptor on human
      granulosa-lutein cells, which is linked to Ca2+ release from intracellular
      stores.

PMID- 7711892
TI  - Injectable testosterone undecanoate has more favourable pharmacokinetics and
      pharmacodynamics than testosterone enanthate.
AB  - Testosterone preparations producing constant physiological testosterone serum
      levels are desirable for long-term treatment of androgen deficiency. However, all
      injectable testosterone esters used clinically for substitution of male
      hypogonadism are characterized by unfavourable pharmacokinetics. We therefore
      tested two groups of five long-term orchidectomized cynomolgus monkeys (Macaca
      fascicularis), which received a single intramuscular injection of 10 mg/kg body
      weight of an injectable testosterone undecanoate (TU) preparation or testosterone
      enanthate (TE) in a preclinical study to assess the pharmacokinetic and
      pharmacodynamic characteristics of TU in comparison to TE. The dose was
      equivalent to 6.3 and 7.2 mg of pure testosterone per kilogram body weight in the
      TU and TE group, respectively. Following injection of TU, mean serum testosterone
      rose to 58 +/- 18 nmol/l on day 1 and remained at moderately supraphysiological
      levels of 40-68 nmol/l for 45 days. Thereafter, testosterone levels were
      maintained in the normal range of intact monkeys for another 56 days. The TE
      injection resulted in highly supraphysiological levels of 100-177 nmol/l from
      immediately after the injection to day 5. A rapid decline followed and
      testosterone levels reached the lower limit of normal after 31 days. Serum
      testosterone levels were significantly higher in the TE-than in the TU-treated
      animals on days 0.5-7 (p < 0.05). Significantly lower testosterone levels were
      seen in the TE than in the TU group on days 16, 22, 25 and 31 (p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711893
TI  - Carbapenem antibiotic production in Erwinia carotovora is regulated by CarR, a
      homologue of the LuxR transcriptional activator.
AB  - Strain GS101 of Erwinia carotovora makes the carbapenem antibiotic, 1-carbapen-2
      em-3-carboxylic acid. Mutants defective in antibiotic production can be assigned
      to two groups, group 1 and group 2. Group 2 mutants are defective in the carl
      gene encoding a protein responsible for synthesis of the Lux autoinducer N-(3
      oxohexanoyl)-L-homoserine lactone (OHHL), which is required to induce carbapenem
      synthesis in strain GS101. In this paper we describe the molecular genetic
      analysis of the group 1 mutants which we presumed were defective in the
      carbapenem biosynthesis (car) genes. We isolated a cosmid (cWU142) that
      complemented the group 1 mutants of strain GS101. A small (1.03 kb) subclone of
      cWU142 complemented most of the group 1 mutants, and the sequence revealed that
      the relevant gene (carR) encodes a homologue of the Vibrio fischeri LuxR protein.
      A disproportionately high frequency of carR mutants arose in strain GS101 and
      this was due to carR acting as a 'hot spot' target for secondary transposition of
      a Tn5 element in this strain. The CarR protein joins a rapidly growing list of
      homologues, found in taxonomically unrelated bacteria, which act as positive
      transcriptional activators of genes encoding diverse metabolic functions,
      including bioluminescence, exoenzyme virulence factor synthesis, cell division,
      plasmid conjugation, rhizosphere-specific gene induction, surfactant synthesis
      and antibiotic production. Most of these LuxR-type regulators have been shown to
      depend, for their function, on N-acyl homoserine lactones, which act as chemical
      signals enabling co-ordination of gene expression with cell density.

PMID- 7711894
TI  - A gene from Alcaligenes denitrificans that confers albicidin resistance by
      reversible antibiotic binding.
AB  - Albicidin antibiotics specifically block prokaryote DNA replication. The
      albicidin resistance gene (albB) cloned from a soil isolate of Alcaligenes
      denitrificans encodes a 23 kDa protein capable of detoxifying albicidin by
      reversible binding. This mechanism operates intracellularly to protect DNA
      replication in albicidin-sensitive Escherichia coli expressing the cloned
      resistance gene, which can be induced fivefold in the presence of 1.5 micrograms
      albicidin ml-1 in the surrounding medium. The coding region of 621 bp has regions
      with partial DNA sequence homology to an albicidin resistance gene (albA) from
      Klebsiella oxytoca, but with rearrangements and frame-shifts resulting in loss of
      protein homology. There is a short region of N-terminal homology between the
      albicidin resistance (Albr) proteins from A. denitrificans and K. oxytoca,
      although the two genes use different codons for shared amino acids. The N
      terminal homology suggested a common functional domain; this was confirmed by
      deletion analysis, translational fusions and albicidin binding by a synthetic
      oligopeptide. Antibiotic binding provides a high level of albicidin resistance in
      E. coli. The gene appears to be a useful candidate for transfer to plants to
      protect plastid DNA replication from inhibition by albicidin phytotoxins involved
      in sugarcane leaf scald disease.

PMID- 7711895
TI  - Surface polysaccharide mutants of Rhizobium sp. (Acacia) strain GRH2: major
      requirement of lipopolysaccharide for successful invasion of Acacia nodules and
      host range determination.
AB  - Two transposon Tn5-induced mutants of wild-type broad-host-range Rhizobium sp.
      GRH2 were isolated and found to harbour different alterations in surface
      polysaccharides. These mutants, designated GRH2-14 and GRH2-50, induced a few,
      empty nodules on Acacia and lost the ability to nodulate most host herbaceous
      legumes. Whereas mutant GRH2-14 produces an acidic exopolysaccharide (EPS)
      similar to the wild-type, the acidic EPS of mutant GRH2-50 lacks galactose and
      the pyruvyl and 3-hydroxybutyryl substituents attached to this sugar moiety. In
      addition, both mutants GRH2-50 and GRH2-14 were altered in smooth
      lipopolysaccharides (LPS). DNA sequence analyses of the corresponding Tn5
      insertions revealed that strain GRH2-50 was mutated in a DNA locus homologous to
      galE, and in vitro enzyme assays indicated that the UDPglucose 4-epimerase (GalE)
      activity was missing in this mutant strain. DNA hybridization studies showed that
      the GRH2-50 mutant DNA has homologous sequences within the different biovars of
      Rhizobium leguminosarum. However, no DNA homology to GRH2-14 altered DNA was
      found in those rhizobial strains, indicating that it represents a new chromosomal
      lps locus in Rhizobium sp. (Acacia) involved in symbiotic development.

PMID- 7711896
TI  - Synthesis of glycerophosphorylated cyclic (1,2)-beta-glucans in Rhizobium
      meliloti strain 1021 after osmotic shock.
AB  - The transfer of phosphoglycerol moieties from phosphatidylglycerol to the cyclic
      (1,2)-beta-glucans in growing cultures of Rhizobium meliloti strain 1021 was
      investigated using pulse-chase experiments with [3H]glycerol and/or [14C]glucose.
      No transfer occurred when cells were grown and pulse-chased in a medium
      containing 0.4 M NaCl. However, radiolabelled glycerophosphorylated cyclic (1,2)
      beta-glucans could be detected within 30 min after transfer of these cultures to
      a low-osmolarity medium. Conversely, when low-osmolarity cultures were shifted to
      a high-osmolarity medium containing 0.4 M NaCl or 0.8 M sucrose, the transfer of
      phosphoglycerol substituents to the cyclic (1,2)-beta-glucans was inhibited.
      Further experiments revealed that the transfer of phosphoglycerol substituents to
      the cyclic (1,2)-beta-glucans occurs within the periplasmic compartment.

PMID- 7711897
TI  - Identification of a 29 kDa flagellar sheath protein in Helicobacter pylori using
      a murine monoclonal antibody.
AB  - The membrane-like flagellar sheath of Helicobacter pylori is of unknown function
      and little is known of its composition. A murine monoclonal antibody to H.
      pylori, designated GF6, which reacts by immunoblot with a polypeptide with an
      apparent molecular mass of 29 kDa was shown by immunogold-electron microscopy to
      label specifically the flagellar sheath structure. The antigen was detected by
      immunoblot using the monoclonal antibody in all 11 strains, of diverse geographic
      origin, so far tested. The antibody also reacted weakly with polypeptides with
      apparent molecular masses of 65 kDa in Vibrio cholerae and Vibrio
      parahaemolyticus. The antigen was shown by one- and two-dimensional
      electrophoretic analysis and immunoblotting to be distinct from the abundant
      urease subunit UreA, of similar molecular mass. Identification of this flagellar
      sheath polypeptide will facilitate investigation of the structure and function of
      the flagellar sheath of this important gastric pathogen.

PMID- 7711898
TI  - Reversible expression of motility and flagella in Clostridium chauvoei and their
      relationship to virulence.
AB  - Clostridium chauvoei strain Okinawa produced spontaneous non-motile variants at
      an unusually high rate (approx. 10(-4) per generation) under normal conditions
      without mutagen. Revertants of non-motile variants were detected at a rate of
      approximately 10(-3). Biochemically, every variant corresponded well with the
      parental strain. By transmission electron microscopy, three of nine non-motile
      variants of strain Okinawa were found to be flagellate, while the other six were
      found to be aflagellate. These phenotypes were confirmed by Western blot analysis
      using monoclonal antibodies directed against the flagella of C. chauvoei.
      Moreover, the parental flagellate strain and non-motile flagellate variants were
      significantly more virulent in mice than non-motile, aflagellate variants. Our
      results demonstrated that phase variation in motility and flagellation occurs in
      C. chauvoei, and that the flagella are associated with the full expression of
      virulence.

PMID- 7711899
TI  - Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents is
      modulated by the mtrRCDE efflux system.
AB  - The mtr (multiple transferable resistance) system of Neisseria gonorrhoeae
      determines levels of gonococcal resistance to hydrophobic agents (HAs), including
      detergent-like fatty acids and bile salts that bathe certain mucosal surfaces.
      The genetic organization of the mtr system was determined and found to consist of
      the mtrR gene, which encodes a transcriptional regulator (MtrR), and three
      tandemly linked genes termed mtrCDE. The mtrCDE genes were organized in the same
      apparent transcriptional unit, upstream and divergent from the mtrR gene. The
      mtrCDE-encoded proteins of N. gonorrhoeae were analogous to a family of bacterial
      efflux/transport proteins, notably the MexABOprK proteins of Pseudomonas
      aeruginosa and the AcrAE and EnvCD proteins of Escherichia coli, that mediate
      resistance to drugs, dyes, and detergents. Inactivation of the mtrC gene resulted
      in loss of the MtrC lipoprotein and rendered gonococci hypersusceptible to
      structurally diverse HAs; this revealed the importance of the mtr system in
      determining HAR in gonococci. Further support for a role of the mtrCDE gene
      complex in determining levels of HAR in gonococci was evident when transformants
      bearing mutations in the mtrR gene were analysed. In this respect, missense and
      null mutations in the mtrR gene were found to result in increased levels of MtrC
      and HAR. However, high levels of MtrC and HAR, similar to those observed for
      clinical isolates, were associated with a single bp deletion in a 13 bp inverted
      repeat sequence that intervened the divergent mtrR and mtrC genes. We propose
      that the 13 bp inverted-repeat sequence represents a transcriptional control
      element that regulates expression of the mtrRCDE gene complex, thereby modulating
      levels of gonococcal susceptibility to HAs.

PMID- 7711900
TI  - Relatedness of penicillin-resistant Streptococcus pneumoniae serogroup 9 strains
      from France and Spain.
AB  - Pulsed-field gel electrophoresis of the genomic DNA of penicillin-resistant
      strains of Streptococcus pneumoniae was carried out. Eleven clinical strains of
      serogroup 9 from different French towns and Paris hospitals were tested. The
      restriction enzymes Apal and Smal were used to digest intact chromosomes, and the
      fragments were resolved by field-inversion gel electrophoresis (FIGE). Five
      strains were similar using Apal and Smal. Four others were closely related when
      using Apal, and five others were closely related when using Smal. These results
      suggest that 10 of these strains are genetically related and have a clonal
      origin. The profile of the eleventh strain was completely different. Thus, in a
      given serotype the spreading of penicillin resistance can result from both clonal
      and independent events. Five strains had similar FIGE profiles to strains first
      isolated in Spain, suggesting that a resistant strain had spread from Spain to
      France.

PMID- 7711901
TI  - Bacillus thuringiensis protoxin: location of toxic border and requirement of non
      toxic domain for high-level in vivo production of active toxin.
AB  - Insecticidal crystal proteins, or protoxins, of Bacillus thuringiensis are
      composed of two domains, an amino-terminal half essential for toxicity, and a
      carboxy-terminal half with an as yet unassigned function. To define the boundary
      of the two domains, sequential termination codons were introduced from the 3'-end
      of the DNA sequence encoding the toxic domain of the 1155-residue cry1A(b) gene
      product. The mutated and the intact genes were placed under the control of the
      Escherichia coli inducible promoter PrecA, and toxicity of the cell extracts was
      determined using silkworm larvae. Under non-induced conditions, in which the gene
      products accumulated to a limited degree, mutations encoding 606 amino acid
      residues or more were toxic, whereas those encoding 605 residues or less were non
      toxic. Comparison of the toxicities and the levels of the toxic proteins
      suggested that the mutant proteins had comparable activity to that of the intact
      protoxin. Furthermore, the non-toxic protein seemed to be unstable in the
      extracts. To investigate the roles of the non-toxic domain, the mutant proteins
      were overproduced in both E. coli and B. thuringiensis. The intact and the
      mutated genes carrying natural promoters were introduced into acrystalliferous B.
      thuringiensis. Upon induction of PrecA in E. coli, and upon sporulation in B.
      thuringiensis, there was a large accumulation of gene products which formed
      inclusion bodies. The inclusion bodies of the intact protoxin were active,
      whereas those of the mutant proteins were inactive. Inclusion bodies of the
      intact protein could be solubilized in alkali, whereas the mutant inclusion
      bodies were insoluble. Since solubilization under alkaline conditions in the
      insect midgut is considered to be the first step of toxic action, the non-toxic
      domain is required to direct the synthesis of inclusion bodies as an active
      soluble form.

PMID- 7711902
TI  - The Bacillus subtilis dnaC gene encodes a protein homologous to the DnaB helicase
      of Escherichia coli.
AB  - Within the region of the Bacillus subtilis chromosome assigned to us in the
      genome sequencing project, we found a gene, the product of which is similar to
      the DnaB protein (replicative DNA helicase) of Escherichia coli. Three B.
      subtilis dna gene mutations, dnaC30 and ts56 causing defects in elongation and
      ts199 causing a defect in the initiation of replication, were mapped in the gene
      by transformation and DNA sequencing. Both dnaC30 and ts56 have been located near
      the amino-terminal end of the B. subtilis DnaC protein. In contrast, ts199 has
      been located near the carboxy-terminal of the protein. Our results indicate that
      the B. subtilis dnaC gene encodes a counterpart of the E. coli dnaB helicase.

PMID- 7711903
TI  - A putative new peptide synthase operon in Bacillus subtilis: partial
      characterization.
AB  - A large operon-type structure has been located between the gltA and citB loci on
      the Bacillus subtilis chromosome. On the basis of the analysis of the 25 kb
      sequenced so far, it potentially encodes at least three large proteins which
      contain structural motifs associated with the subunits of all characterized
      peptide synthases. The amino acid recognition specificity of this new peptide
      synthase is discussed in the light of sequence homology with other synthases.

PMID- 7711904
TI  - Effects of signal peptide mutations on processing of Bacillus stearothermophilus
      alpha-amylase in Escherichia coli.
AB  - Bacillus stearothermophilus alpha-amylase has a signal peptide typical for
      proteins exported by Gram-positive bacteria. There is only one signal peptidase
      processing site when the protein is exported from the original host, but when it
      is exported by Escherichia coli, two alternative sites are utilized. Site
      directed mutagenesis was used to study the processing in E. coli. Processing
      sites for 13 B. stearothermophilus alpha-amylases carrying mutations in their
      signal peptide were determined. Processing of the signal peptide was remarkably
      tolerant to mutations, because switching between the alternative sites was
      possible. The length and the sequence of the region between the hydrophobic core
      and the cleavage site was crucial for determining the choice of the processing
      site. Some mutations more distal to the cleavage site also affected the site
      preference.

PMID- 7711905
TI  - Lagging-strand origins of the promiscuous plasmid pMV158: physical and functional
      characterization.
AB  - The streptococcal plasmid pMV158 replicates by a rolling circle mechanism, which
      involves the generation of single-stranded plasmid DNA intermediates. This
      plasmid has the unique feature of having two lagging-strand origins of
      replication. One of these origins, termed ssoU, is functional in Streptococcus
      pneumoniae and in Bacillus subtilis in an orientation-dependent manner. The other
      origin, ssoA, is only functional in the former host. RNA polymerase seems to be
      involved in the initiation of the conversion of single- to double-stranded
      plasmid DNA from both ssoA and ssoU. Mutational and deletion analyses have
      allowed us to define ssoA as being within a highly structured, non-coding 199 bp
      region. Within this region, two elements which are conserved in several rolling
      circle replicating plasmids are located, the recombination site RSB and a 6 base
      consensus sequence. Both elements may play a role in the conversion of single- to
      double-stranded plasmid DNA.

PMID- 7711906
TI  - Activation of cytoplasmic trehalase by cyclic-AMP-dependent and cyclic-AMP
      independent signalling pathways in the yeast Candida utilis.
AB  - Derepressed cells of Candida utilis suspended in buffer exhibited both a
      transient cAMP-mediated signal and a marked activation of cytoplasmic trehalase
      when supplemented with glucose. Nitrogen sources or protein synthesis inhibitors,
      as well as protonophores or uncouplers, were also able to cause trehalase
      stimulation in derepressed cells even in the absence of the sugar. The increase
      in trehalase activity caused by nitrogen sources or protein synthesis inhibitors
      was not accompanied by changes in cAMP levels. Moreover, acridine orange
      inhibited both the cAMP signal and the glucose-induced activation of trehalase
      without affecting the increase in trehalase activity caused by nitrogen sources
      or protein synthesis inhibitors. These results suggest that cAMP is not involved
      as second messenger in the signal for trehalase stimulation induced by the latter
      compounds. By contrast, the addition of glucose to repressed cells suspended in
      buffer failed to cause the cAMP-mediated glucose signal and sugar-induced
      trehalase activation. No significant changes in either trehalase activity or cAMP
      concentration were observed upon addition to these cells of asparagine,
      cycloheximide, anisomycin or other agents, including protonophores and
      uncouplers. However, heat treatment of repressed cultures resulted in a moderate
      increase in trehalase activity with negligible change in cAMP levels, whereas
      such an effect was not observed in derepressed cultures. The thermally induced
      increase in trehalase activity was dependent on de novo protein synthesis and
      required the presence of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711907
TI  - Induction of heat, freezing and salt tolerance by heat and salt shock in
      Saccharomyces cerevisiae.
AB  - Stress tolerance of Saccharomyces cerevisiae was examined after exposure to heat
      and salt shock in the presence or absence of the protein synthesis inhibitor
      cycloheximide. Cells heat-shocked (37 degrees C for 45 min) in the absence of
      cycloheximide demonstrated increased tolerance of heat, freezing and salt stress.
      For cells heat-shocked in the presence of cycloheximide, heat and salt tolerance
      could still be induced, although at lower levels, while induction of freezing
      tolerance was completely inhibited. These results indicated that while heat shock
      proteins (hsps) may contribute to induced heat and salt tolerance they are not
      essential, although induction of freezing tolerance appears to require protein
      synthesis. Exposure of cells to salt shock (300 mM NaCl for 45 min) induced
      stress protein synthesis and the accumulation of glycerol, responses analogous to
      induction of hsp synthesis and trehalose accumulation in cells exposed to heat
      shock. Cells salt-shocked in the absence of cycloheximide showed a similar
      pattern of induced stress tolerance as with heat, with increased tolerance of
      heat, salt and freezing. Cells salt-shocked in the presence of cycloheximide
      continued to show induced heat and salt tolerance, but freezing tolerance could
      not be induced. These results lend support to the hypothesis that hsp synthesis
      is not essential for induced tolerance of some forms of stress and that
      accumulated solutes such as trehalose or glycerol may contribute to induced
      stress tolerance.

PMID- 7711908
TI  - Mini-chromosomes in Fusarium sporotrichioides are mosaics of dispersed repeats
      and unique sequences.
AB  - Variations in trichothecene patterns of 26 Fusarium sporotrichioides isolates
      from different plant and geographic origins showed no correlation with
      electrophoretic karyotype polymorphisms. When intact chromosomes were examined,
      interisolate karyotype differences were observed only in the mini-chromosome
      range. Further polymorphisms were revealed in Notl-digested samples. By summing
      the Notl fragments the average genome size of F. sporotrichioides was estimated
      to be 20.4 Mb. Mini-chromosomes shared common sequences with the larger ones;
      however, clones (RMS-1 and RMS-2) specific to these structures have also been
      found. These clones contained no coding region and no promising similarities were
      observed when they were compared to sequences held at GenBank. Mini-chromosomes
      in F. sporotrichioides constitute a mosaic composed of dispersed repeats and
      unique sequences. This mosaic structure was maintained in all noninterbreeding,
      genetically isolated strains examined.

PMID- 7711909
TI  - Carbon-arsenic bond cleavage by a newly isolated gram-negative bacterium, strain
      ASV2.
AB  - Strain ASV2, an unidentified Gram-negative bacterium newly isolated from
      activated sludge, was found to utilize arsonoacetate at concentrations up to at
      least 30 mM as sole carbon and energy source, with essentially quantitative
      extracellular release of arsenate. Cell-free conversion of arsonoacetate could
      not be obtained, but resting-cell studies indicated that the carbon-arsenic bond
      cleavage activity was inducible in the presence of arsonoacetate and was of
      limited substrate specificity, also breaking down arsonochloroacetate. The
      inorganic product of the reaction may be arsenite since an inducible arsenite
      oxidizing activity was also found in arsonoacetate-metabolizing cells. This is
      the first report of a micro-organism capable of utilizing a compound containing
      the carbon-arsenic bond. The results indicate that the ability of bacteria to
      degrade arsonoacetate is not fortuitous and may be found in environments not
      previously exposed to organoarsenicals.

PMID- 7711910
TI  - 23Na NMR spectroscopy of free Na+ in the halotolerant bacterium Brevibacterium
      sp. and Escherichia coli.
AB  - 23Na NMR spectroscopy was used to determine free Na+ concentrations in a
      halotolerant bacterium, Brevibacterium sp., and Escherichia coli. The internal
      Na+ concentration of both strains depended little on the growth phases and was
      unchanged after 5 d storage at 2 degrees C. In Brevibacterium sp. the level of
      intracellular sodium increased gradually at higher extracellular NaCl
      concentrations in both the presence and absence of yeast extract in the growth
      medium. E. coli cells accumulated a higher concentration of free Na+ than those
      of Brevibacterium sp. The change of Na+ concentration in both strains was inverse
      to that of growth rate. When appropriate amounts of osmoprotectants (proline,
      glycine betaine, or gamma-aminobutyrate) were added with the NaCl, internal free
      Na+ levels in Brevibacterium sp. were lowered, but those of E. coli were
      unchanged. While addition of KCl to medium containing NaCl increased the
      intracellular level of free Na+, the total sodium concentration in the cells
      remained unchanged, indicating that sodium that had been bound or attached was
      made free in the cytosol. In Brevibacterium sp. grown in the presence of 0.5 M
      NaCl, free and bound sodium concentrations in the cytosol were estimated to be
      0.14 and 0.23 mumol (mg protein)-1, respectively. As a result, visibility by 23Na
      NMR was 38%.

PMID- 7711911
TI  - Use and effectiveness of transdermal nicotine in primary care settings.

PMID- 7711912
TI  - Screening for cobalamin deficiency.

PMID- 7711913
TI  - Screening for cobalamin deficiency.

PMID- 7711914
TI  - Prostate cancer screening.

PMID- 7711915
TI  - Lessons from quantifying futility.

PMID- 7711916
TI  - Israeli physical activity study.

PMID- 7711917
TI  - Prostate cancer screening. What family physicians believe is best.
AB  - OBJECTIVE: To determine current family physician beliefs concerning prostate
      cancer screening. DESIGN: Two hundred eighty-six Oklahoma family physicians were
      surveyed by mail. Fifty-three percent of physicians returned the questionnaire.
      Physicians were questioned on what tests they order for prostate screening, the
      reasons for ordering a serum prostate-specific antigen (PSA) test, what test
      results would cause a urologic referral for further evaluation of prostate
      cancer, and whether prostate cancer screening would decrease the patient's
      mortality or improve quality of life. RESULTS: Most physicians (74%) believed
      that both a digital rectal examination and a serum PSA determination are
      appropriate for prostate cancer screening. Physicians' primary reasons for
      ordering a PSA test were to decrease patient mortality and morbidity. Sixty-two
      percent of physicians believed that prostate cancer screening would decrease
      mortality and 69% agreed that screening would improve quality of life.
      Approximately 90% of physicians would refer patients with a PSA level greater
      than 12 micrograms/L or a PSA level of 5 micrograms/L and an indurated prostate.
      Significant variation was found between groups of physicians in their beliefs
      about prostate cancer screening. CONCLUSION: Although the literature has been
      inconclusive on the benefit of prostate cancer screening, the majority of
      Oklahoma family physicians would choose to screen their patients and believe that
      patients' mortality and morbidity are decreased by early identification of
      prostate cancer.

PMID- 7711918
TI  - Self-reported physical activity predicts long-term coronary heart disease and all
      cause mortalities. Twenty-one-year follow-up of the Israeli Ischemic Heart
      Disease Study.
AB  - OBJECTIVE: To determine whether self-reported physical activity predicts a
      decreased rate of coronary heart disease (CHD) and all-cause mortalities in
      middle-aged men when rates are adjusted for known confounders. DESIGN: Cohort
      Analytic Study of Israeli government employees in 1963. SUBJECTS: Eight thousand
      four hundred sixty-three Israeli male government employees, aged 40 years or
      older, representing six areas of birth, excluding those with known cardiovascular
      disease in either 1963 or 1965, from an original cohort of 10,059. MAIN OUTCOME
      MEASURE: Comparison of rates of death due to CHD and all causes, determined from
      death certificates in 21 years of follow-up, for subjects with different baseline
      levels of self-reported leisure-time and work-related physical activities
      measured in 1965. RESULTS: Self-reported leisure-time but not work-related
      physical activity was inversely related to both CHD (adjusted relative risk,
      0.79; 95% confidence interval, 0.66 to 0.95) and all-cause mortalities (adjusted
      relative risk, 0.91; 95% confidence interval, 0.83 to 0.99). Most of the apparent
      benefit accrued was from light physical activity on less than a daily basis.
      These inverse relationships persisted after adjustment for age, systolic blood
      pressure, cigarette smoking, total and high-density lipoprotein cholesterol
      levels, body mass index, psychosocial factors, and other potential confounders.
      CONCLUSION: Baseline levels of self-reported leisure-time physical activity
      predicted a decreased rate of CHD and all-cause mortalities in employed middle
      aged Israeli men followed up prospectively for 21 years.

PMID- 7711919
TI  - Differences in the frequency of cholesterol screening in patients with Medicaid
      compared with private insurance.
AB  - OBJECTIVE: To assess compliance with preventive screening for Medicaid recipients
      compared with individuals with equal access to preventive services. SETTING: A
      community-based family practice residency program. METHODS: Survey of a
      consecutive sample of English-reading individuals, aged 18 to 50 years, with
      Medicaid (n = 98) or private insurance (n = 75), who had scheduled appointments
      in the clinic. MAIN RESULTS: Patients with Medicaid were as likely as those with
      private insurance to be screened for hypertension and cervical cancer in the last
      5 years but were less likely to have received cholesterol screening (39% vs 65%,
      P < .001). Even after adjusting for differences in gender composition, age, race,
      marital status, and education level attained, patients with Medicaid were still
      less likely to have received cholesterol screening (odds ratio, 0.43; 95%
      confidence interval, 0.21 to 0.57). Although patients with Medicaid were no more
      likely to identify a barrier and, when identifying barriers, did not identify
      significantly more barriers than patients with private insurance, Medicaid
      recipients were less likely to state that cholesterol testing had been
      recommended by their physician (30% vs 44%, P = .05). CONCLUSIONS: Because access
      to screening tests by patients with Medicaid is equal to or better than that of
      those with insurance, differences in the frequency of cholesterol screening
      should not reflect financial barriers. Differences in the attention paid to
      screening by physicians and differences in cultural beliefs about the importance
      of screening may play a role in the underuse of screening services by individuals
      in lower socioeconomic groups.

PMID- 7711920
TI  - Patient perceptions of physician acceptance of gifts from the pharmaceutical
      industry.
AB  - OBJECTIVE: To examine patient perceptions of professional appropriateness and the
      potential impact on health care of physician acceptance of gifts from the
      pharmaceutical industry. DESIGN: A random-digit dialing telephone survey. SETTING
      AND PARTICIPANTS: A sample of 649 adults (> or = 18 years old) living in
      Kentucky. MAIN OUTCOME MEASURES: Patient awareness of office-use gifts (eg, pens,
      notepads) and personal gifts to physicians from the pharmaceutical industry,
      patient exposure to office-use gifts, and attitudes toward physician acceptance
      of both office-use and personal gifts. RESULTS: The survey had a response rate of
      55%. Eighty-two percent of the respondents were aware that physicians received
      office-use gifts, while 32% were aware that physicians received personal gifts.
      Seventy-five percent reported receiving free samples of medication from their
      physicians. Compared with office-use gifts, more respondents believed that
      personal gifts to physicians have a negative effect on both health care cost (42%
      vs 26%) and quality (23% vs 13%). After controlling for demographic variables, as
      well as awareness and exposure to physician gifts, individuals with at least a
      high school education were 2.4 times as likely to believe that personal gifts
      have a negative effect on the cost of health care and 2.3 times as likely to
      believe that personal gifts would have a negative effect on the quality of health
      care. CONCLUSIONS: These results suggest that the public is generally uninformed
      about personal gifts from pharmaceutical companies to physicians. If public
      perception regarding the objectivity of the medical profession is to serve as a
      guide, these findings suggest a reevaluation may be in order for guidelines
      regarding physician acceptance of gifts from the pharmaceutical industry.

PMID- 7711921
TI  - The negative pregnancy test. An opportunity for preconception care.
AB  - OBJECTIVE: To identify women who would likely benefit from preconception care.
      METHODS: A comprehensive preconception risk survey was administered during a
      structured interview to 136 women who had a negative pregnancy test visit in a
      family practice residency ambulatory practice. The survey solicited the presence
      of self-reported risk variables associated with maternal conditions related to
      poor obstetric outcome, risk factors for poor obstetric outcome, and risks for
      developing these conditions. RESULTS: Seventy women (51.5%) reported a medical or
      reproductive risk that could adversely affect pregnancy. In addition, 68 women
      (50%) reported a genetic risk; 39 (28.7%) reported a risk for human
      immunodeficiency virus infection, 35 (25.7%) reported an indication for hepatitis
      B vaccine, and an equal number reported recent use of illegal substances; 23
      (16.9%) reported at least one affirmative answer to the CAGE questionnaire; 79
      (58.5%) smoked cigarettes; 74 (54.4%) reported a nutrition risk; 126 (92.6%)
      reported a psychosocial risk; and 39 (28.7%) reported a perceived barrier to
      ongoing medical care. Even with the psychosocial risk category excluded, 94% of
      the women still reported at least one factor requiring further evaluation,
      counseling, or intervention before pregnancy. CONCLUSIONS: We discovered a
      significant number of women with obstetric risk factors. A negative pregnancy
      test visit provides an opportunity for preconception risk assessment and
      counseling. These results will guide us to further develop practical
      preconception care protocols.

PMID- 7711922
TI  - Site-to-site variation in the factors affecting cesarean section rates.
AB  - OBJECTIVE: To investigate the influence of various factors, including physician
      specialty, on the risk of cesarean birth. DESIGN: Retrospective medical chart
      review. PARTICIPANTS: Review of 7367 deliveries at five hospitals in five
      different states. MAIN OUTCOME MEASURE: Method of delivery. RESULTS: Logistic
      regression modeling using clinical and demographic risk factors found that the
      risk factors that influence cesarean delivery varied considerably among different
      hospitals. Only primiparity (relative risk, 2.22 to 5.81 among sites) and
      multiple gestation (relative risk, 4.74 to 100.48 depending on the site) were
      associated with increased cesarean delivery in all sites. Private insurance,
      preeclampsia, and having an obstetrician as the primary medical provider were
      also independently associated with cesarean delivery in four sites. Examination
      of 50 other variables showed no consistent independent associations with cesarean
      delivery. CONCLUSIONS: The clinical and nonclinical factors that influence
      cesarean section are highly site dependent. This implies that physicians
      practicing at different sites are influenced by different criteria when deciding
      whether a cesarean delivery should be performed.

PMID- 7711923
TI  - When everything is too much. Quantitative approaches to the issue of futility.
AB  - Although physicians agree broadly that there is no obligation to provide futile
      care, there is no consensus, of which I am aware, regarding a definition of
      futility. Two quantitative approaches to determining futility are proposed,
      neither of which involves financial costs. First, based on the number of
      consecutive failures of an intervention, it is possible to calculate the
      probability of success for the next attempted treatment. The second method uses
      quality-adjusted life years to balance the burden and benefit of a specific
      treatment and to determine the probability of success beneath which the treatment
      is futile. When applied to the use of in-hospital cardiopulmonary resuscitation
      in patients with metastatic cancer, both of these methods confirm the futility of
      this intervention.

PMID- 7711924
TI  - Colorectal cancer. A practical review for the primary care physician.
AB  - Colorectal cancer is a common disease in the United States. In the past 30 years,
      only limited improvements in stage of disease at the time of diagnosis and
      survival rates have been made. Research into genetic, environmental, and diet
      related risk factors is promising but insufficient to serve as a foundation for
      preventive advice. The slowly progressive adenoma-carcinoma sequence is now
      commonly accepted. The American Cancer Society, Atlanta, Ga, and the National
      Cancer Institute, Bethesda, Md, advocate screening with annual fecal occult blood
      testing plus sigmoidoscopy every 3 to 5 years in persons 50 years old and older.
      The development of more cost-effective screening strategies is under study, with
      emphasis on targeting high-risk populations, determining optimal screening
      intervals, identifying the length of colon to study and by what means, and
      determining the surveillance needed in individuals who have had polyps removed.

PMID- 7711925
TI  - Possible concentration-dependent suppression of immune response by verapamil.
AB  - Calcium channel blockers inhibit in vitro the lymphocyte response to mitogens and
      the generation of cytotoxic T-cell and natural killer cell activity. We report on
      a patient taking verapamil hydrochloride who experienced repeated, prolonged
      viral infections. His lymphocyte response to phytohemagglutinin, pokeweed
      mitogen, and tetanus antigen were suppressed; the mononuclear response to soluble
      tetanus was markedly diminished; and there was no response to influenza
      vaccination. On lowering the verapamil dose, or changing therapy to clonidine
      hydrochloride, all the above-mentioned functions returned to normal and a
      response to influenza vaccination was observed. We speculate that the prolonged
      viral infection observed in this patient may have been caused by suppression of
      the immune response by verapamil and we encourage further boad-based studies.

PMID- 7711926
TI  - The relationship between glycine and gephyrin in synapses of the rat spinal cord.
AB  - In order to examine the relationship between gephyrin (the peripheral membrane
      protein associated with glycine receptors) and glycinergic boutons, we have
      carried out a post-embedding immunogold study of glycine-like immunoreactivity on
      sections of rat lumbar spinal cord which had previously been reacted with
      monoclonal antibody to gephyrin. In all three areas examined (laminae I and II,
      lamina III and lamina IX) the majority of profiles which were presynaptic at
      gephyrin-immunoreactive synapses were enriched with glycine-like
      immunoreactivity. It was estimated that at least 83% of profiles presynaptic to
      gephyrin-immunoreactive synapses in the superficial dorsal horn (laminae I and
      II) were glycine-immunoreactive, while for lamina III and the ventral horn
      (lamina IX) the proportions were at least 91% and 98% respectively. This provides
      strong evidence that glycine is a transmitter at those synapses where gephyrin-
      and glycine-like immunoreactivities are both present, but suggests that gephyrin
      may sometimes be expressed at non-glycinergic synapses and indicates the need for
      caution in using gephyrin-immunoreactivity as a marker for glycinergic synapses
      within the spinal cord. By reacting serial sections of dorsal horn with antisera
      to glycine and GABA, we have shown that many boutons in laminae I-III of the
      dorsal horn show both types of immunoreactivity and are therefore likely to use
      both amino acids as inhibitory transmitters. Many of the boutons which were
      presynaptic at axoaxonic synapses in the ventral part of lamina II and in lamina
      III were glycine- and GABA-immunoreactive and in many cases the postsynaptic
      element was the central axon of a type II synaptic glomerulus. Taken together
      with pharmacological evidence, this suggests that inhibitory interneurons in the
      dorsal horn which use both GABA and glycine may be important in controlling the
      flow of information from hair follicle afferents to other spinal neurons.

PMID- 7711927
TI  - Quantitative comparison of the transient rescue effects of neurotrophic factors
      on axotomized motoneurons in vivo.
AB  - A reproducible neuronal degeneration induced by nerve lesion in neonatal rats or
      mice provides a convenient in vivo assay for testing the survival-promoting
      activity of putative growth factors on motoneurons. The goal of this study was to
      compare the rescue effects of the four known neurotrophins [nerve growth factor
      (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and
      neurotrophin-4 (NT-4)] and two of the cytokines [ciliary neurotrophic factor
      (CNTF) and leukaemia inhibitory factor (LIF)] in one particular experimental
      model of spinal motoneuron degeneration at two different survival times. The
      sciatic nerve was cut in neonatal rats and the factors were applied onto the
      nerve stump; bovine serum albumin was used in controls. Simultaneous application
      of the retrograde tracer fluoro-gold made it possible to count motoneurons
      specifically in the sciatic pool. One week after lesion, the neurotrophins BDNF,
      NT-3 and NT-4, but not NGF, equally enhanced motoneuron survival compared to
      controls; their effects were significantly better than those of the cytokines.
      However, the rescue from cell death was only transitory because a great number of
      the motoneurons died during the second week after nerve lesion. Additional BDNF
      and/or CNTF supplied by repeated subcutaneous injections (1 mg/ml) over 2 weeks
      could not prevent this delayed motoneuron loss. These results suggest that still
      other factors or alternative routes of administration may be required for
      permanent rescue of the lesioned immature motoneurons.

PMID- 7711928
TI  - Developmentally regulated expression of mRNA for neurotrophin high-affinity (trk)
      receptors within chick trigeminal sensory neurons.
AB  - To investigate the distribution of neurons within the developing trigeminal
      sensory system which express mRNA for each of the three known high-affinity
      neurotrophin receptors (trk, trkB and trkC), we have performed in situ
      hybridization histochemistry on serial sections through the trigeminal ganglion
      and trigeminal mesencephalic nucleus at various ages of development using
      specific antisense oligonucleotide probes. We show that trkC mRNA is first
      expressed in the chicken embryo at stage 13, in presumptive neurons prior to the
      formation of the ganglion, that trkB mRNA labelling is initially observed within
      peripheral neurons slightly later, at stage 19, and that trk mRNA expression is
      not detectable until around embryonic day 3.5 (stage 21/22). The neurons which
      exhibit mRNA labelling for each of the high-affinity receptors occupy discrete
      regions within the ganglion, indicating that the ganglion comprises distinct
      neuronal subpopulations, each of which has a different capacity to respond to the
      different neurotrophins. Neurons which express trk mRNA are confined to the
      proximal region of the ganglion, whereas those which express trkB mRNA and trkC
      mRNA are located in two distinct regions within the distal aspect and also within
      the trigeminal mesencephalic nucleus. From the estimation of the number of
      neurons which exhibit labelling between embryonic days 9 and 18, we determined
      that the expression of mRNA for the high-affinity receptors changes during
      embryonic development of the ganglion. This is consistent with the observed
      differences in the response to neurotrophins in vitro.

PMID- 7711929
TI  - Morphine selectively depresses the slowest, NMDA-independent component of C-fibre
      evoked synaptic activity in the rat spinal cord in vitro.
AB  - The effects of morphine on the depolarizing synaptic responses produced in
      motoneurons by electrical stimulation of primary sensory neurones have been
      recorded in hemisected spinal cord preparations (8- to 12-day-old rat pups).
      Morphine at concentrations of 0.1-20 microM reduced a slow, long-lasting (latency
      greater than 1 s, duration up to 10 s) component of the ventral root potential
      (VRP) evoked by C-fibre strength stimulation of the dorsal root. At 2 microM the
      reduction in area of this slow synaptic potential was 71.7 +/- 0.9% of control
      values (n = 15). The earliest components of the C-fibre strength VRP (the first
      100 ms) and the responses to A beta strength stimuli were unaffected by the
      opioid even at 10-20 microM. The intermediate, NMDA receptor antagonist (D-AP5,
      40 microM)-sensitive component (which lasts 100-1000 ms) was reduced by 34 +/-
      2.2% of control (n = 15), which was significantly less than the reduction of the
      later NMDA-independent component (P < 0.001). Morphine (0.1-20 microM) also
      depressed the cumulative depolarization generated by the temporal summation of
      synaptic responses evoked by brief trains of C-fibre strength stimuli (1 or 10
      Hz). A significantly greater reduction at the lower frequency of stimulation
      (56.3 +/- 2.0%) than at the higher (20.3 +/- 1.69%, n = 10, measured at 2 microM
      morphine) was found (P < 0.005). The effects of morphine were reversible upon
      wash-out or superfusion with the opioid receptor antagonist naloxone (2
      microM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711930
TI  - Evidence for the existence of a functional polysynaptic pathway from trigeminal
      afferents to lumbar motoneurons in the neonatal rat.
AB  - Stimulation of trigeminal afferents has been reported to have powerful effects on
      the spinal cord in adult animals of several species. In the present study, the
      pathway transmitting these influences was investigated in the neonatal rat.
      Experiments were performed on in vitro brainstem/spinal cord preparations.
      Stimulation of the trigeminal nerve evoked bilateral polysynaptic discharges in
      lumbar ventral roots. Intracellular recordings from lumbar motoneurons showed
      mainly excitatory responses, although a few inhibitory responses were also
      observed. Experiments with perfusion of different parts of the preparation with
      general or selective synaptic blockers revealed a synaptic relay under GABAergic
      control in the brainstem, and at least one synapse in the cervical and in the
      thoracic spinal cord. The involvement of lumbar interneurons was established by
      perfusing the lumbar enlargement with saline containing either a high
      concentration of divalent ions or mephenesin in order to reduce transmission
      along polysynaptic pathways. The contribution of excitatory amino acid
      transmission was evaluated and was found to evoke mixed receptor responses. The
      course of the pathway was traced by using different lesions to the brainstem and
      spinal cord. The pathway was found to be ipsilateral in the brainstem and to
      become bilateral in the spinal cord. The results of the present study demonstrate
      that polysynaptic sensorimotor pathways are present at birth. The results are
      discussed in relation to the pontomedullary locomotor strip, which has been
      thought to share many features with the trigeminal system.

PMID- 7711931
TI  - NGF deprivation of adult rat brain results in cholinergic hypofunction and
      selective impairments in spatial learning.
AB  - Cholinergic hypofunction has often been correlated with a variety of behavioural
      impairments. In the present study, adult Wistar rats were intraventricularly
      infused with antibodies to nerve growth factor (anti-NGF) to examine the effects
      on cholinergic neurons of the basal forebrain, and on behavioural performance.
      Immunocytochemical techniques indicated that chronically infused anti-NGF
      penetrates into the basal forebrain, cortex, striatum, corpus callosum and
      hippocampus, confirming previous findings after a single injection. Treatment
      with anti-NGF for 1 or 2 weeks resulted in a significant decrease of 27-33% in
      density of choline acetyltransferase immunostaining of the cholinergic cell
      bodies in the medial septum and vertical diagonal band, and a 26% reduction in
      choline acetyltransferase enzyme activity in the septal area. An array of spatial
      learning Morris water maze tasks was used to distinguish between acquisition
      skills and the flexible use of learned information in novel tests. Rats subjected
      to the spatial learning paradigm received anti-NGF infusion for 2 weeks prior to
      and for another 2 weeks during the behavioural testing. The anti-NGF-treated
      animals were found to be no different from those receiving control serum in the
      Morris water maze acquisition task, either in the latency to find the platform or
      in the time spent searching in the training quadrant when the platform was
      removed. However, in consecutive extinction trials, anti-NGF rats continued to
      search in the empty training quadrant, suggesting the occurrence of
      perseveration; control rats expanded their search over other areas of the
      pool.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7711932
TI  - Functional neuroanatomy of the human visual fixation system.
AB  - The regional cerebral blood flow correlates of the active fixation of an imagined
      target were studied in five healthy humans using the positron emission tomography
      activation paradigm. The fixation task was contrasted to a passive control
      condition, both tasks being performed in total darkness. Blood flow increases
      were observed in the frontal eye fields and supplementary eye fields and in the
      median cingulate gyrus. We suggest that the network of these activated regions
      mediates the interactions between ocular fixation, eye movements and directed
      visual attention.

PMID- 7711933
TI  - Corticothalamic projections from the cortical barrel field to the somatosensory
      thalamus in rats: a single-fibre study using biocytin as an anterograde tracer.
AB  - This study investigated the pattern of axonal projections of single
      corticothalamic neurons from the cortical barrel field representing the vibrissae
      in the rat. Microiontophoretic injections of biocytin were performed in cortical
      layers V and VI to label small pools of corticothalamic cells and their
      intrathalamic axonal projections. After a survival period of 48 h, the animals
      were perfused and the tissue was processed for biocytin histochemistry. On the
      basis of the intrathalamic distribution of axonal fields and of the types of
      terminations found in the thalamus, four types of corticothalamic projections
      were identified. (i) Cells of the upper part of layer VI projected exclusively to
      the ventral posteromedial (VPm) nucleus, where they arborized in long
      rostrocaudally oriented bands or 'rods'. (ii) All cells of the lower part of
      layer VI projected to the medial part of the thalamic posterior group (Pom) but
      the vast majority of them also collateralized in VPm where they participated in
      the formation of rods. (iii) A minority of corticothalamic cells in the lower
      portion of layer VI, possibly located under the interbarrel spaces (septae),
      arborized exclusively in Pom. (iv) The corticothalamic projection of layer V
      cells originated from collaterals of corticofugal cells whose main axons ran
      caudally towards the brainstem. These collaterals arborized exclusively in Pom or
      in the central lateral nucleus. All corticothalamic cells from layer VI displayed
      the same type of axonal network, made of long branches decorated by terminal
      buttons emitted en passant at the tip of fine stalks. Corticothalamic fibres
      arising from layer V pyramids, however, remained smooth as they ran across the
      lateral thalamus and they generated in Pom one or two clusters of large boutons.
      All corticothalamic axons derived from layer VI cells, but not those derived from
      layer V cells, gave off collaterals as they traversed the thalamic reticular
      complex. These observations are discussed in the light of previous studies
      bearing on the topological organization and function of corticothalamic
      projections to VPm and Pom in rats. The possibility that a similar cellular
      specificity and a similar organizational plan may characterize corticothalamic
      relationships in other sensory systems is also considered.

PMID- 7711934
TI  - The axonal arborization of single thalamic reticular neurons in the somatosensory
      thalamus of the rat.
AB  - This study describes the axonal projections of single neurons of the thalamic
      reticular complex within the somatosensory thalamic nuclei in rats. Experiments
      were performed under urethane anaesthesia and reticular cells were labelled by
      extracellular microiontophoretic applications of biocytin. The axonal
      arborization of 25 thalamic reticular cells projecting to the ventrobasal (VB)
      nucleus and/or to the posterior thalamic (Po) complex were reconstructed from
      serial horizontal sections. Reticular cells labelled with biocytin display
      somatodendritic features similar to those reported previously. Their cell body is
      fusiform and their dendrites bear few spines and show a high degree of streaming
      along the horizontal curved axis of the nucleus. In most cells, axon-like beaded
      processes stem out from dendrites but, contrary to previous descriptions, no
      intrareticular axonal collateral was observed. The axonal arborization of most
      thalamic reticular cells is confined within the limits of a single thalamic
      nucleus; only two neurons were seen projecting to both the VB and the Po nuclei.
      In VB, termination fields form short rods (diameter approximately 150 microns,
      length approximately 200-300 microns) densely packed with grape-like boutons and
      varicosities; termination fields in Pro are larger, much less dense, and they are
      contained within a horizontal slab of tissue (thickness approximately 200
      microns, mediolateral width approximately 400 microns, rostrocaudal length
      approximately 1 mm. By charting the position of all labelled cells within the
      thickness of the thalamic reticular complex, a strip-like arrangement was
      revealed. Cells projecting to Po occupy the innermost portion of the nucleus
      whereas those projecting to the ventral-posteromedial and ventral-posterolateral
      nuclei are located respectively in the middle and in the outer tiers of the
      nucleus. This strip-like reciprocity was confirmed by separate biocytin
      injections performed in VB and in Po. These results show that inhibition of
      reticular origin is distributed within the rat dorsal thalamus in a highly
      specific manner, most likely according to a principle of reciprocity within the
      somatotopic representation of the body.

PMID- 7711935
TI  - Effect of SR33557 on intramembrane charge movement in normal and 'muscular
      dysgenesis' mouse skeletal muscle cells.
AB  - It has been reported that the indolizinsulphone SR33557, which binds to a site on
      the alpha 1 subunit of the dihydropyridine receptor, blocks both L-type calcium
      channel activity and contraction in skeletal muscle. Moreover, we know that
      charge movement plays a key role in the mechanism of excitation-contraction
      coupling and in controlling the opening of L-type calcium channels. We
      demonstrate here that SR33557 reduces intramembrane charge movement in skeletal
      muscle from normal mice with an IC50 of approximately 10 nM. The drug does not
      completely inhibit charge movement since approximately 20% of total charge
      movement persists even in the presence of 30 microM SR33557. However, the SR33557
      sensitive charge component is more important than the dihydropyridine-sensitive
      one. Surprisingly, SR33557 also reduces intramembrane charge movement in dysgenic
      myotubes which are characterized by a very strong reduction of the number of
      dihydropyridine binding sites. In these muscles, 10 microM SR33557 reduces
      approximately 40% of total charge movement. These observations suggest the
      presence of a new component of charge movement which is sensitive to SR33557 but
      insensitive to nifedipine. This component is also present in dysgenic myotubes,
      and it could be produced by the lower molecular weight alpha 1 subunit described
      by Malouf, N. N., McMahon, D. K., Hainsworth, C. N. and Kay, B. K. (1992)
      (Neuron, 8, 899-906).

PMID- 7711936
TI  - Receptors and second messengers involved in long-term depression in rat
      cerebellar slices in vitro: a reappraisal.
AB  - In patch-clamped Purkinje cells (PCs), bath application of the ionotropic
      glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)
      prevents induction of long-term depression (LTD) of parallel fibre (PF)-mediated
      EPSPs by a pairing protocol between Ca2+ spike firing and PF stimulation whereas
      bath application of (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), a
      metabotropic glutamate (mGLU) receptor antagonist, does not. On the other hand,
      LTD can be also induced by pairing direct depolarization of PCs with activation
      of mGLU receptors by 1S,3R-aminocyclopentyl-dicarboxylate (1S,3R-ACPD), even in
      the presence of CNQX. In this case, LTD induction is not consistently blocked by
      bath application of the nitric oxide synthase inhibitor, NG-methyl-L-arginine (L
      NMMA), whereas it is strongly blocked when the protein kinase C inhibitor peptide
      19-36 is dialysed into PCs. These results are at variance with LTD induced by a
      pairing protocol between Ca2+ spikes and PF-mediated EPSPs which depends to the
      same extent on both cascades. Finally, thapsigargin, which depletes most
      intracellular Ca2+ pools, does not block induction of LTD by a pairing protocol
      between Ca2+ spikes and PF-mediated EPSPs whereas it prevents the induction of
      LTD depending on strong mGLU receptor activation.

PMID- 7711937
TI  - Associative synaptic potentials in the piriform cortex of the isolated guinea-pig
      brain in vitro.
AB  - The involvement of local and remote associative fibres in the generation of
      piriform cortex synaptic potentials was investigated in the isolated guinea-pig
      brain maintained in vitro by arterial perfusion by implementing current source
      density analysis (CSD) on cortical field potential profiles. Previous hypotheses
      were verified using acute surgical isolation of piriform cortical areas to study
      different synaptic events separately. Stimulation of the lateral olfactory tract
      activated associative potentials throughout the piriform cortex. In the anterior
      piriform cortex, the current sinks responsible for the generation of associative
      potentials were located in the superficial portion of layer Ib and in layer III.
      In the posterior piriform cortex, two associative events were observed: an early
      sink located in the superficial part of layer Ib, followed by a sink in the deep
      part of the same layer. In the anterior piriform cortex, local associative
      synaptic potentials were separated from the component carried by long projective
      fibres by surgically isolating a small area of cortex monosynaptically activated
      by lateral olfactory tract stimulation. In this patch of lateral olfactory tract
      connected anterior piriform cortex, local associative sinks were observed in the
      superficial Ib layer and in layer III. Monosynaptic activation of the isolated
      patch of anterior piriform cortex induced purely associative potentials
      throughout the piriform cortex. These potentials were mediated by the synaptic
      activation of apical dendrites in the superficial Ib layer and selectively
      abolished by severing the long associative fibres. The anterior piriform cortex
      layer III sink and the posterior piriform cortex deep Ib associative component
      were evoked by the activation of large population spikes in the monosynaptic
      anterior piriform cortex and the disynaptic posterior piriform cortex response
      respectively. These two sinks are presumably generated locally through a
      polysynaptic circuit, whose activation depends on the degree of cortical
      excitation. Olfactory signal processing in the guinea-pig piriform cortex during
      states of normal excitability is supported by the interactions between
      associative inputs impinging on the synapses located separately on the dendrites
      of pyramidal neurons. An increase in the synchronization of piriform cortex
      neuron discharge activates usually silent local circuit synapses.

PMID- 7711938
TI  - Alternative RNA splicing generates diversity of neuropeptide expression in the
      brain of the snail Lymnaea: in situ analysis of mutually exclusive transcripts of
      the FMRFamide gene.
AB  - In the CNS of the snail Lymnaea stagnalis, Phe-Met-Arg-Phe-amide (FMRFamide)-like
      and additional novel neuropeptides are encoded by a common, multi-exon gene. This
      complex locus, comprising at least five exons, is subject to post-transcriptional
      regulation at the level of alternative RNA splicing. Our aim was first to analyse
      the pattern by which exons of this neuropeptide locus combine during splicing of
      the primary RNA transcript, and second to investigate the functional significance
      of splicing by mapping the expression and neuronal localization in the CNS of the
      alternative mRNA transcripts, in the context of defined neuronal networks and
      single identified neurons. The approach was a combination of comparative in situ
      hybridization and immunocytochemistry, using a battery of exon-specific
      oligonucleotides and anti-peptide antisera. The analysis illustrated that exons
      III, IV and V were always coexpressed and colocalized whereas the expression of
      exon II was always differential and mutually exclusive. Both sets of exons were,
      however, coexpressed with exon I: the total number of exon I-expressing neurons
      was equal to the combined number of neurons expressing exon III/IV/V and neurons
      expressing exon II. In addition, it was revealed that the extreme 5' of exon II,
      encoding a potential hydrophobic leader signal, was not expressed in the CNS of
      Lymnaea but was apparently spliced out during RNA processing. Both mRNA
      transcripts of the FMRFamide locus, type 1 (exons I/II) and type 2 (exons
      I/III/IV/V), were translated in the CNS and the resulting protein precursors were
      also expressed in a mutually exclusive fashion, as were their respective
      transcripts. The expression of alternative transcripts within identified networks
      or neuronal clusters was heterogeneous, as exemplified by the cardiorespiratory
      network. On the basis of this work and a previous cDNA analysis, we put forward a
      revised model of differential splicing and expression of the FMRFamide gene in
      the CNS of Lymnaea.

PMID- 7711939
TI  - Fibroblast growth factors and insulin growth factors combine to promote survival
      of rat Schwann cell precursors without induction of DNA synthesis.
AB  - In embryonic rat nerves, we recently identified an early cell in the Schwann cell
      lineage, the Schwann cell precursor. We found that when these cells were removed
      from contact with axons they underwent rapid apoptotic death, and that in a
      proportion of the cells this death could be prevented by basic fibroblast growth
      factor (bFGF, FGF-2). We now report that 100% of Schwann cell precursors isolated
      from peripheral nerves of 14-day-old-rat embryos can be rescued by a combination
      of insulin-like growth factor (IGF) 1 or 2 in combination with either acidic FGF
      (aFGF, FGF-1), bFGF or Kaposi's sarcoma FGF (K-FGF; FGF-4). The precursors
      display an absolute requirement for both an IGF and an FGF to achieve maximal
      survival. Elevation of intracellular levels of cAMP by forskolin does not result
      in a significant shift in the IGF/FGF dose-response curves. In contrast, the
      percentage of precursors rescued by FGF in the presence of insulin is
      dramatically increased by elevation of cAMP. These growth factor combinations did
      not stimulate DNA synthesis significantly in Schwann cell precursors. These
      findings show that cooperation between growth factors is required to suppress
      cell death in Schwann cell precursors, and suggest that survival and DNA
      synthesis are regulated by distinct growth factor combinations in these cells.
      The observations are consistent with the idea that survival regulation by FGFs
      and IGFs plays an important role in the development of glial cells in early
      embryonic nerves.

PMID- 7711940
TI  - Synchronous high-frequency oscillations in cat area 18.
AB  - The present study extends knowledge of the basic properties of correlated
      oscillatory activity patterns in the visual cortex of anaesthetized cats.
      Recordings with multiple electrodes were performed in area 18 and the
      correlations of multi-unit activity in the frequency range 35-80 Hz were
      determined using the coherence function. Statistical analysis revealed that the
      multi-unit correlations depended on the cortical distance between the recording
      sites, the orientation selectivity of the neurons and their cortical layer. On
      average, correlations dropped to chance level within several millimetres and were
      higher in lower than in upper cortical layers. Similar results were found by
      analysing the correlations of oscillatory patterns in local field potentials
      recorded from the same electrodes. Correlations of neurons with similar
      orientation preferences were higher than those of neurons with different
      orientation preferences. Comparison to a matched sample from area 17 showed that
      the correlations in areas 18 and 17 depended on similar properties of the
      neurons. The dependences of correlated oscillations resembled the known pattern
      and specificity of intra-areal fibre connections, suggesting that the
      correlations were intracortically established. Since correlations were
      specifically and not randomly related to the response properties of cortical
      neurons and were prominent in a visual area other than area 17, the findings
      suggest that correlated oscillatory activity provides a potential neural code
      supporting sensory information processing.

PMID- 7711941
TI  - Effect of collicular proteoglycan on the survival of adult rat retinal ganglion
      cells following axotomy.
AB  - Consistent with numerous previous studies, we have found that in adult rats 29%
      of cells retrogradely prelabelled by injections into retino-recipient nuclei are
      lost 1 week after intraorbital section of the optic nerve. This figure increases
      to 76% 2 weeks after axotomy. Intraocular injections of 150 ng of 480 kDa
      chondroitin sulphate proteoglycan purified from the superior colliculi of
      neonatal rats were performed every third day after axotomy. This procedure
      resulted in the loss of only 3 and 28% of the axotomized retinal ganglion cells 7
      and 14 days respectively after optic nerve section. Intraocular injections of
      chondroitin sulphate type C, one of the sugar types present on the collicular
      proteoglycan, also resulted in a significant saving of axotomized ganglion cells
      (with the loss of only 48% 14 days after optic nerve lesion). These findings
      suggest that the collicular proteoglycan, and to a lesser extent its sugar
      moieties, substantially slows down the degeneration of adult retinal ganglion
      cells following axotomy.

PMID- 7711942
TI  - Vestibular bibliography.

PMID- 7711943
TI  - The effect of head tilt on perception of self-orientation while in a greater than
      one G environment.
AB  - The effect of head tilt on the perception of self-orientation while in a greater
      than one G environment was studied in nine subjects using the Armstrong
      Laboratory Dynamic Environment Simulator. After a 12-s stabilization period at a
      constant head tilt and G level, subjects reported their perception of the horizon
      by placing their right hand in a position they believed to be horizontal. Head
      tilt conditions ranged from -30 degrees to +45 degrees pitch over each of three
      head yaw positions. G levels ranged from one to four and were in the longitudinal
      axis of the body (Gz). Hand position was recorded in both the pitch and roll body
      axes. A function of head tilt did improve the fit of a multiple regression model
      to the collected data in both the pitch and roll axes (P < .05). The best fit was
      accomplished with a nonlinear function of G and head pitch. When the head
      remained level but the environment tilted with respect to the G vector (at angles
      similar to those perceived during head tilt), subjects accurately reported the
      environmental tilt. Head tilt under G can result in vestibular-based illusionary
      perception of environmental tilt. Actual environmental tilt is accurately
      perceived due to added channels of haptic information.

PMID- 7711944
TI  - Visual hallucinations evoked by caloric vestibular stimulation in normal humans.
AB  - This study describes a hitherto unknown phenomenon in healthy humans: visual
      hallucinations evoked by caloric vestibular stimulation. The hallucinations are
      of elementary type. The following quantitative and qualitative characteristics of
      the hallucinatory images were measured: latency, duration, location in the visual
      field, relation to the provoked vertigo, colour of the hallucinatory image and
      the background, number, size, shape, distance from the eyes, and motion. Two
      mechanisms are proposed to explain the genesis of these hallucinations. One
      mechanism is direct: change in the spontaneous activity of the visual system in
      several levels; the other mechanism is indirect: transient haemodynamic
      disturbance in the visual system.

PMID- 7711945
TI  - Reliability of psychophysiological responses across multiple motion sickness
      stimulation tests.
AB  - Although there is general agreement that a high degree of variability exists
      between subjects in their autonomic nervous system responses to motion sickness
      stimulation, very little evidence exists that examines the reproducibility of
      autonomic responses within subjects during motion sickness stimulation. Our
      objectives were to examine the reliability of autonomic responses and symptom
      levels across five testing occasions using the (1) final minute of testing, (2)
      change in autonomic response and the change in symptom level, and (3) strength of
      the relationship between the change in symptom level and the change in autonomic
      responses across the entire motion sickness test. The results indicate that,
      based on the final minute of testing, the autonomic responses of heart rate,
      blood volume pulse, and respiration rate are moderately stable across multiple
      tests. Changes in heart rate, blood volume pulse, respiration rate, and symptoms
      throughout the test duration are less stable across the tests. Finally, autonomic
      responses and symptom levels are significantly related across the entire motion
      sickness test.

PMID- 7711946
TI  - The subjective visual vertical as a clinical parameter of vestibular function in
      peripheral vestibular diseases.
AB  - The subjective visual vertical, SV, was measured in the upright and side
      positions in 25 normal subjects and in 73 patients with various peripheral
      vestibular disorders. Significant deviations of SV (toward the affected ear) were
      found in 100% of the patients with vestibular nerve section and with Ramsay Hunt
      syndrome, in 89% of the patients with vestibular neuritis, and in 0% of the
      patients with benign paroxysmal positional vertigo. The deviation of SV gradually
      disappeared within a few weeks of the onset of the disease in all patients except
      in those with total VIIth nerve resection. SV is a parameter of tonic afferent
      differences between the two labyrinths similar to vestibular spontaneous
      nystagmus but is mediated by other parts of the inner ear (probably the otolith
      organs) and thus provides additional information on the labyrinthine function. SV
      measured in 90 degrees side positions, however, did not reveal asymmetric
      vestibular sensitivity, which is in contrast to SV tested during eccentric
      rotation in patients after vestibular neurectomy.

PMID- 7711947
TI  - Bilateral loss of eighth nerve function as the only clinical sign of
      vertebrobasilar dolichoectasia.
AB  - The case of a 55-year-old female is presented, in whom first a loss of the
      vestibular and hearing function on the left side occurred with sudden onset, and
      3 days later an additional loss of functions on the right side occurred. No other
      neurological symptoms were present. Angiography and MRI scan revealed
      vertebrobasilar dolichoectasia with a thrombus attached to the wall of the
      basilar artery. Anticoagulative therapy improved hearing function on the right
      side sufficiently to allow conversation. Vestibular organs remained unresponsive
      to caloric irrigation. This bilateral loss of eighth nerve function is discussed
      as a rare case of bilateral ischemia of the labyrinthine artery due to basilar
      dolichoectasia.

PMID- 7711948
TI  - Betahistine dihydrochloride treatment facilitates vestibular compensation in the
      cat.
AB  - Unilateral lesion of the vestibular system induces posturo-locomotor deficits
      that are compensated for with time. Drug therapy is currently used to improve the
      recovery process and to facilitate vestibular compensation. Betahistine
      dihydrochloride is an histamine-like substance that has been employed in
      vestibular pathology; it was found effective in many forms of vertigo and in
      vestibular-related syndromes. Investigations performed in animal models have
      shown betahistine-induced neuronal modulations in the vestibular nuclei complex
      and interactions with the H1 and H3 histamine receptors. Potentially, this
      substance is therefore capable to interfere with some recovery mechanisms and to
      improve the behavioral adaptations. But there is at present a total lack of data
      concerning the influence of betahistine treatment on vestibular compensation in
      animal models. The aim of this study was to understand the pharmacological
      activity of betahistine in the restoration of posture and locomotor balance
      functions in unilateral vestibular neurectomized cats. Posture recovery was
      assessed by quantifying the surface reaction of the cat's support as measured
      while standing erect on its four legs, at rest. Locomotor balance recovery was
      determined using the rotating beam test, by measuring the maximal performance
      (max. P.) of the cat and its locomotion speed regulation during the postoperative
      time period. We have compared the recovery profile and time course of these
      static (posture) and dynamic (equilibrium) functions in three groups of cats. Two
      experimental groups were treated at daily doses of 50 mg/kg and 100 mg/kg,
      respectively. Betahistine dihydrochloride was given orally until complete
      recovery of posturolocomotor functions. One untreated control group served as the
      reference. Results showed that postoperative treatment strongly accelerated the
      recovery process in both treated groups, inducing a time benefit of around 2
      weeks as compared to the controls. Maximum performance of the cats on the
      rotating beam as well as locomotion speed regulation were highly correlated to
      the postoperative development of the cat's support surface, indicating that
      compensation of the static vestibulospinal deficits conditioned the subsequent
      locomotor balance recovery. These behavioral data showed that betahistine
      dihydrochloride constitutes a useful drug therapy for the symptomatic treatment
      of central vestibular disorders in our animal model of unilateral vestibular
      lesion. Improvement of vestibular compensation under betahistine postoperative
      treatment, as evidenced here for the posture and locomotor balance functions, is
      discussed both in terms of aspecific effect (histamine-induced increase of the
      level of vigilance) or more direct action in the vestibular nuclei (histamine
      induced rebalance of neuronal activity on both sides).

PMID- 7711949
TI  - Effect of cellular physiology on PCR amplification efficiency.
AB  - Culture conditions, and other variables that modulate a cell's physiology, can
      bias a polymerase chain reaction (PCR) amplification against generating a
      representative population profile. Two Pseudomonas putida nahR alleles were
      constructed in pUC19 that differ solely in a 31-bp internal segment whose
      sequence has been inverted. After PCR amplification, the products could be
      distinguished on the basis of a change in a unique restriction site. When an
      Escherichia coli strain carrying one nahR allele is submitted to different growth
      conditions, the consequences of such variations on the relative PCR amplification
      of whole cells can be ascertained through coamplification with a strain carrying
      the other allele and subsequent restriction analysis. Cells in stationary phase
      displayed improved amplifiability while cells grown at 42 degrees C were equally
      amplifiable as compared to cells grown at 37 degrees C. However, sublethal levels
      of tetracycline or growth in minimal medium made the PCR target in these cells
      relatively less amplifiable. When cells are completely lysed and the plasmid DNA
      is purified beforehand, the coamplification bias is eliminated. These results
      suggest that mixed populations containing cells in different physiological states
      may not be representatively amplified by PCR unless a DNA extraction step is
      included.

PMID- 7711950
TI  - Parentage analysis within a semi-free-ranging group of Barbary macaques Macaca
      sylvanus.
AB  - This study of a group of semi-free-ranging Barbary macaques Macaca sylvanus aimed
      to determine paternity, to establish whether any individual male achieved
      prominent mating success and to assess genetic variability. Analyses involved
      electrophoresis of 15 blood protein systems and multilocus DNA fingerprinting
      (isotopic and nonisotopic). Genetic variability was low; only two blood protein
      systems were polymorphic. Although all DNA-fingerprints were individual-specific,
      they showed a high average band-sharing index value (0.67). Nevertheless, a
      combination of all methods permitted inference of paternity in 11 out of 15 (73%)
      cases tested. Several males from different age classes fathered infants.

PMID- 7711951
TI  - Polymorphic microsatellite DNA markers in the grey red-backed vole Clethrionomys
      rufocanus bedfordiae.

PMID- 7711952
TI  - A set of universal primers for amplification of polymorphic non-coding regions of
      mitochondrial and chloroplast DNA in plants.

PMID- 7711953
TI  - Molecular genetic analysis of the response of three soil microbial communities to
      the application of 2,4-D.
AB  - The responses of three different soil microbial communities to the experimental
      application of 2,4-dichlorophenoxyacetic acid (2,4-D) were evaluated with a
      variety of molecular genetic techniques. Two of the three soil communities had
      histories of prior direct exposure to 2,4-D, and one had no prior direct
      application of any herbicide. Dominant 2,4-D degrading strains isolated from
      these soils the previous year were screened for hybridization with three
      catabolic genes (tfdA, tfdAII, and tfdB) cloned from the well-studied 2,4-D
      degradative plasmid, pJP4, revealing varying degrees of similarity with the three
      genes. Hybridization of total community DNA from the three soils with the tfd
      gene probes also indicated that pJP4-like tfd genes were not harboured by a
      significant percentage of the community. Community level response was evaluated
      by the comparison of different treatments by Random Amplified Polymorphic DNA
      (RAPD) fingerprints and by community DNA cross-hybridization. No differences
      between treatments within the same soil were detected in any of the RAPD
      fingerprints generated with 17 primers. Community DNA cross-hybridization also
      indicated that the application of 2,4-D at the applied rates did not
      quantitatively affect the structure of the soil microbial communities present in
      the three soils during the time-frame studied.

PMID- 7711954
TI  - Postglacial expansion and genome subdivision in the European grasshopper
      Chorthippus parallelus.
AB  - A noncoding nuclear DNA marker sequence (Cpn1-1) was used to investigate
      subdivision in the grasshopper Chorthippus parallelus and deduce postglacial
      expansion patterns across its species range in Europe. Investigation of the
      spatial distribution of 71 Cpn1-1 haplotypes and estimation of levels of genetic
      differentiation (KST values) between populations and geographic regions provided
      evidence for subdivision of C. parallelus into at least five major geographic
      regions and indicated that the French form of C. parallelus originated after
      range expansion from a Balkan refugium. Further evidence for subdivision of C.
      parallelus between Italy and northern Europe suggests that the Alps may have
      formed a significant barrier to gene flow in this grasshopper.

PMID- 7711955
TI  - Generation of RAPD-PCR primers for the identification of isolates of Glomus
      mosseae, an arbuscular mycorrhizal fungus.
AB  - Mycorrhizal fungi are usually identified on the basis of the morphological
      characters shown by fruit bodies, spores, vegetative mycelia or symbiotic
      structures. The development of molecular techniques provides a valuable and
      alternative approach to identify mycorrhizal fungi, especially when it is
      difficult to gather a sufficient number of data on morphological features. Short
      arbitrary oligonucleotides were used as primers for the amplification of genomic
      DNA extracted from spores of arbuscular fungi. The RAPD fingerprints showed
      banding patterns which allowed us to distinguish between species and even
      isolates within Glomales. In order to identify mycorrhizal fungi during their
      symbiotic phase, a nonpolymorphic RAPD band identified as marker for some
      isolates of Glomus mosseae was purified from agarose gels and cloned in a
      bluescript vector. The fragment was sequenced and specific primers (PO-M3) were
      designed for the mycorrhizal fungus. They specifically and successfully amplified
      the DNA not only from G. mosseae spores, but also from roots of pea, clover, leek
      and onion plants when they were colonized by G. mosseae isolates.

PMID- 7711956
TI  - Mitochondrial DNA sequence variation and genetic stock structure of Atlantic cod
      (Gadus morhua) from bay and offshore locations on the Newfoundland continental
      shelf.
AB  - Bay cod, Atlantic cod (Gadus morhua) that over-winter in the deep-water bays of
      north-eastern Newfoundland, have historically been regarded as distinct in
      migration and spawning behaviour from offshore (Grand Bank) cod stocks. To
      investigate their genetic relationships, we determined the DNA sequence of a 307
      base-pair portion of the mitochondrial cytochrome b gene for 236 adult cod taken
      from the waters off north-eastern Newfoundland, including fish found over
      wintering and spawning in Trinity Bay. Although 17 genotypes were found, a single
      common genotype occurs at a frequency of greater than 80% in all samples, and no
      alternative genotype occurs at a frequency of greater than 3%. Genotype
      proportions did not differ significantly among samples. Measures of genetic
      subdivision among sampling locations are nil. Cod over-wintering in Trinity Bay
      are not genetically distinct from offshore cod. In combination with tagging and
      physiological studies, these data suggest that there is sufficient movement of
      cod between bay and offshore locations to prevent the development or maintenance
      of independent inshore stocks. Adult cod that over-winter in Trinity Bay appear
      to represent an assemblage of temporarily nonmigratory fish that have become
      physiologically acclimated to cold-water inshore environments. The pattern of
      genetic variation in northern cod suggests a recent population structure
      characterized by extensive movement of contemporary individuals superimposed on
      an older structure characterized by a bottleneck in the population size of cod in
      the north-western Atlantic.

PMID- 7711957
TI  - Monoandry and polyandry in bumble bees (Hymenoptera; Bombinae) as evidenced by
      highly variable microsatellites.
AB  - Highly variable microsatellites enabled a precise assessment of the number of
      queen matings in the colonies of five bumble bee species. Fifteen of the sixteen
      microsatellites initially cloned from B. terrestris had flanking regions similar
      enough to allow PCR amplification on the other Bombus species analysed. The
      microsatellites selected for intracolony study (four per species) were
      characterized by a high heterozygosity (0.58-0.93) and a large number of alleles
      (3-18) in the local populations from which the colonies originated. A single male
      appeared to have inseminated the queens in the colonies of four species, B.
      terrestris, B. lucorum, B. lapidarius and B. pratorum, which belong to three
      subgenera, whereas two of the three analysed colonies of B. hypnorum were
      polyandrous (minimum number of two and four patrilines, respectively).

PMID- 7711958
TI  - Conservation genetics of the European brown bear--a study using excremental PCR
      of nuclear and mitochondrial sequences.
AB  - In the Brenta area of northern Italy, a brown bear Ursus arctos population is
      rapidly going extinct. Restocking of the population is planned. In order to study
      the genetics of this highly vulnerable population with a minimum of stress to the
      animals we have developed a PCR-based method that allows the study of
      mitochondrial and nuclear gene sequences from droppings collected in the field.
      This method is generally applicable to animals in the wild. Using excremental as
      well as hair samples, we show that the Brenta population is monomorphic for one
      mitochondrial lineage and that female as well as male bears exist in the area. In
      addition, 70 samples from other parts of Europe were studied. As others have
      previously reported, the mitochondrial gene pool of European bears is divided
      into two major clades, one with a western and the other with an eastern
      distribution. Whereas populations generally belong to either one or the other
      mitochondrial clade, the Romanian population contains both clades. The bears in
      the Brenta belong to the western clade. The implications for the management of
      brown bears in the Brenta and elsewhere in Europe are discussed.

PMID- 7711959
TI  - Trio learning: a new strategy for building hybrid neural trees.
AB  - Neural trees are constructive algorithms which build decision trees whose nodes
      are binary neurons. We propose a new learning scheme, "trio-learning," which
      leads to a significant reduction in the tree complexity. In this strategy, each
      node of the tree is optimized by taking into account the knowledge that it will
      be followed by two son nodes. Moreover, trio-learning can be used to build hybrid
      trees, with internal nodes and terminal nodes of different nature, for solving
      any standard tasks (e.g. classification, regression, density estimation).
      Significant results on a handwritten character classification are presented.

PMID- 7711960
TI  - Optimization dynamics for partitioned neural networks.
AB  - Given a relaxation-based neural network and a desired partition of the neurons in
      the network into modules with relatively slow communication between modules, we
      investigate relaxation dynamics for the resulting partitioned neural network. In
      particular, we show how the slow inter-module communication channels can be
      modeled by means of certain transformations of the original objective function
      which introduce new state variables for the inter-module communication links. We
      report on a parallel implementation of the resulting relaxation dynamics, for a
      two-dimensional image segmentation network, using a network of workstations.
      Experiments demonstrate a functional and efficient parallelization of this neural
      network algorithm. We also discuss implications for analog hardware
      implementations of relaxation networks.

PMID- 7711961
TI  - Local noise in neural networks models with self-control.
AB  - We modify neural networks models of the Hopfield type so that they can recognize
      the degree of novelty of the input stimuli on a local level. The networks control
      themselves the quality of recognition and can also recognize locally the bits of
      information in the input patterns which do not agree with known patterns, i.e.
      stored memories. This task is achieved by introducing local variations of the
      noise level beta in the network. Noise level in a given location depends on the
      flip frequency of the neurons close to that location.

PMID- 7711962
TI  - Relationship between a fuzzy logic and a steepest descent approach to optimize a
      feedforward artificial neural network configuration.
AB  - The neural network designer must take into consideration many factors when
      selecting an appropriate network configuration. The performance of a given
      network configuration is influenced by many different factors such as: accuracy,
      training time, sensitivity, and the number of neurons used in the implementation.
      Using a cost function based on the four criteria mentioned previously, the
      various network paradigms can be evaluated relative to one another. If the
      mathematical models of the evaluation criteria as functions of the network
      configuration are known, then traditional techniques (such as the steepest
      descent method) could be used to determine the optimal network configuration. The
      difficulty in selecting an appropriate network configuration is due to the
      difficulty involved in determining the mathematical models of the evaluation
      criteria. This difficulty can be avoided by using fuzzy logic techniques to
      perform the network optimization as opposed to the traditional techniques. Fuzzy
      logic avoids the need of a detailed mathematical description of the relationship
      between the network performance and the network configuration, by using heuristic
      reasoning and linguistic variables. A comparison will be made between the fuzzy
      logic approach and the steepest descent method for the optimization of the cost
      function. The fuzzy optimization procedure could be applied to other systems
      where there is a priori information about their characteristics.

PMID- 7711963
TI  - Discriminative nonlinear dimensionality reduction for improved classification.
AB  - Multi-Layer Perception (MLP) neural networks have been used extensively for
      classification tasks. Typically, the MLP network is trained explicitly to produce
      the correct classification as its output. For speech recognition, however,
      several investigators have recently experimented with an indirect approach: a
      unique MLP predictive network is trained for each class of data, and
      classification is accomplished by determining which predictive network serves as
      the best model for samples of unknown speech. Results from this approach have
      been mixed. In this report, we compare the direct and indirect approaches to
      classification from a more fundamental perspective. We show how recent advances
      in nonlinear dimensionality reduction can be incorporated into the indirect
      approach, and we show how the two approaches can be integrated in a novel MLP
      framework. We further show how these new MLP networks can be usefully viewed as
      generalizations of Learning Vector Quantization (LVQ) and of subspace methods of
      pattern recognition. Lastly, we show that applying these ideas to the
      classification of temporal trajectories can substantially improve performance on
      simple tasks.

PMID- 7711964
TI  - Predictive control of nonlinear systems based on identification by
      backpropagation networks.
AB  - Using the property of universal approximation of multilayer perceptron neural
      network, a class of discrete nonlinear dynamical systems are modeled by a
      perceptron with two hidden layers. A backpropagation algorithm is then used to
      train the model to identify the nonlinear systems to a desired level of accuracy.
      Based on the identified model, a one-step-ahead predictive control scheme is
      proposed in which the future control inputs are obtained through some nonlinear
      optimization process. Making use of the online learning properties of neural
      networks, the predictive control scheme is further developed into an adaptive one
      which is robust to the incompleteness of identification. Simulation results show
      that this neural control scheme works well even for some very complicated
      nonlinear systems.

PMID- 7711965
TI  - A hybrid cognitive system using production rules to synthesize neocognitrons.
AB  - A hybrid cognitive system is proposed where a working neocognitron is synthesized
      with a set of production rules. The knowledge base of a neocognitron is
      constructed through incorporating production rules into its interlayer
      connections. Training for prototype patterns is not required. The semantic of
      interlayer connections is established. The resulting network can now be analyzed
      according to the rule structure and problematic portions can be corrected.
      Neocognitrons constructed using this hybrid approach have been tested on the same
      set of handwritten numerals initiated by Fukushima with scaling and skewing
      distortions, and with noise contamination. It is found that the performance is
      comparable to that of Fukushima's network obtained by supervised training.

PMID- 7711966
TI  - Handwritten digit recognition using two-layer self-organizing maps.
AB  - In this paper, we present a two-layer self-organizing neural network based method
      for handwritten digit recognition. The network consists of a base layer self
      organizing map and a set of corresponding maps in the second layer. The input
      patterns are partitioned into subspace in the first layer. Patterns in a subspace
      are led to the second layer and a corresponding map is built according to the
      first layer performance. In the classification process, each pattern searches for
      several closest nodes from the base map and then it is classified into a
      specified class by determining the nearest model of the corresponding maps in the
      second layer. The new method yielded higher accuracy and faster performance than
      the ordinary self-organizing neural network.

PMID- 7711967
TI  - Cancer continues to be a focus for action at national, European and international
      levels.

PMID- 7711968
TI  - Terminal care: improving teamwork in primary care using Significant Event
      Analysis.
AB  - Significant Event Analysis can be used to improve the effectiveness of a Primary
      Health Care Team caring for terminally ill patients. A method of doing this is
      described in detail. Positive team qualities were confirmed and enhanced.
      Significant areas for improvement were identified: insufficient information had
      been given to some key workers, changes in medication had been poorly planned,
      continuity of care, and emotional and professional support of team members were
      inadequate. A strategy for change was developed and implemented. Performance was
      reviewed a year later. It was found that the Significant Event Analysis had
      caused changes in team practices, and was valid and reliable enough to be used as
      a tool for improving teamwork in primary care in future.

PMID- 7711969
TI  - Palliative medicine and the medicalization of death.
AB  - The emergence of the speciality of palliative medicine in the UK has been
      generally welcomed and can be seen as a continuation of the attempts to improve
      the care of dying people begun by the modern hospice movement. However, not
      everyone has welcomed the new speciality unreservedly. In part, this reflects a
      more general ambivalence and concern about the role of medicine in terminal care.
      After a brief discussion of the 'medicalization' of death and an overview of the
      hospital care of dying people, the paper identifies five concerns about the
      development of the speciality of palliative medicine in Britain. These are: the
      lack of clarity about its remit; a potential shift of focus away from terminal
      care; the inappropriate use of medical technology; the role of other health
      workers; the consequences for hospice care.

PMID- 7711970
TI  - Pause for thought: nurses use research--don't they?
AB  - The issues surrounding nurses and their use of research are many and complex.
      Experience in a newly developing area of nursing--the management of lymphodema-
      has revealed three key reasons why nurses do not, on the whole, use the research
      process to answer clinical problems or use the results of research to change
      clinical practice. First, nurses tend not to see research as their own
      responsibility; secondly, they tend not to read on a regular basis; and finally,
      nurses are neither taught nor encouraged to think critically about what they do.
      The situation can be improved if senior nurses make a positive effort to foster
      an atmosphere of enquiry, report research findings in a language all can
      understand, and encourage fellow nurses in the pursuit of knowledge.

PMID- 7711971
TI  - Education in palliative care: a qualitative evaluation of the present state and
      the needs of general practitioners and community nurses.
AB  - A questionnaire survey was carried out of all general practitioners, community
      hospital nurses and community nurses working in Worcester Health District in the
      west of England, to assess the present state and future needs of their education
      in palliative care. The overall response rate of the survey was 72%. The
      respondents were an experienced group of doctors and nurses. They felt that their
      undergraduate or basic training did not prepare them to care for dying patients
      in the community. Educational needs were identified: control of symptoms other
      than pain and bereavement care were priorities for doctors. Community hospital
      nurses rated pain control education as a major need. Alternative medicine and
      caring for dying children were additional areas for further education for the
      general practitioner and community nurses. Ninety per cent of general
      practitioners, 84% of community hospital nurses and 95% of community nurses felt
      that multi-disciplinary teaching sessions would be helpful. Analysis of their
      responses revealed that these would be most likely to succeed it they were
      arranged in the middle of the day during lunch or in the evenings. The doctors
      felt that they lacked protected learning time. Nurses also felt this, but in
      addition, identified lack of finance as a limiting factor in their post-basic
      education. There was evidence that existing educational resources in the district
      are under-utilized.

PMID- 7711972
TI  - Assessment and measurement of pain.
AB  - This paper provides an overview of issues relating to pain assessment and
      management. Areas to be covered include the problems involved in assessing pain
      as a subjective phenomenon, the constraints of assessment within the clinical
      field, factors that affect pain, and pain assessment tools and questionnaires.
      The aim of the reference list is to provide back-up reading to assist in
      exploring the options available when considering the possibility of compiling a
      pain assessment protocol for individual clinical areas.

PMID- 7711973
TI  - Pain control: some aspects of day-to-day management.
AB  - A practical framework for the management of pain control in palliative care of
      patients with advanced malignancies, using analgesics and co-analgesics is
      described. The analgesic ladder is used as a model for the logical progression of
      options for the day-to-day application of analgesics. Strong opioids and their
      side-effects are discussed. Indications for the most frequently applied co
      analgesics are given, including the more commonly required psychotropic agents.

PMID- 7711974
TI  - Patient choice in management. Drug and Therapeutics Bulletin, Consumers'
      Association, London, UK.
AB  - All treatments carry risks as well as potential benefits. For patients with
      cancer, management decisions have to consider the quality of survival, as well as
      the prolonging of life and choices about treatment which are often particularly
      stark. Participation in these decisions helps some patients adapt to their
      illness, increases their satisfaction with medical care and promotes acceptance
      of the treatment (Brody, 1980). For other patients it can impose undue
      responsibility and confusion, heighten anxiety or undermine trust in the doctor
      (Ingelfinger, 1986). Where does the balance lie?

PMID- 7711975
TI  - The attitudes of newly qualified house officers towards palliative care.

PMID- 7711976
TI  - Cancer prevention in the UK.
AB  - There has been concerted action in the UK to reduce mortality and morbidity from
      cancer, especially lung cancer. With the evolution and development of positive
      health promotion through life-style programmes, many aspects of the Europe
      Against Cancer programme's 10-point code for living are integrated into existing
      programmes. Whilst health promotion programmes in the UK have, for many years,
      concentrated on the promotion of positive health, the priority for action to
      reduce deaths from cancer has been focused on lung cancer. The UK government's
      report on the health of the nation has provided a further endorsement of
      education programmes aimed to reduce deaths from cancer.

PMID- 7711977
TI  - Europe Against Cancer: Cancer Week UK.
AB  - Since the beginning of the Europe Against Cancer (EAC) programme in 1989, much
      support and emphasis has been given to informing both health professionals and
      the public about cancer. This has come from the government and the many cancer
      related charities and organizations. A week focused on cancer throughout the
      European Union (EU) has been encouraged each October. This paper describes the
      gradual development of these weeks to provide a more planned, co-ordinated and
      evaluated strategy. Collaboration with European partners is also addressed,
      emphasizing the positive benefits of such activities. Finally, the issue of
      monitoring and evaluation is addressed in some detail.

PMID- 7711978
TI  - Cancer communication: the health promotion challenge.
AB  - The way of communicating messages about cancer is the essence of this paper.
      There is a challenge to promote health, and demystify misconceptions about cancer
      and its treatment. But how do you reach those who seldom read or who are
      illiterate? How do you convince people that early presentation of symptoms that
      may be caused by cancer can positively influence outcome? How can you present a
      practical and realistic message about life-style factors and cancer? This paper
      explains initiatives in the UK to address some of these issues. The role of
      research and evaluation is important, but so are the ethical issues when you may
      be trying to persuade and convince the public of the benefits of life-style
      change. Finally, the issue of training of health professionals is addressed.

PMID- 7711979
TI  - Distance learning materials in cancer prevention: a European project.

PMID- 7711980
TI  - Open learning in palliative care.
AB  - Open learning is increasing in importance in nurse education. In this article the
      author considers open learning and discusses its use in palliative care
      education. Advantages and disadvantages of this learning method are considered
      and guidelines are offered to the teacher to assist them to evaluate existing
      learning packages or to produce their own open learning materials.

PMID- 7711981
TI  - Beyond cancer: changes, problems and needs expressed by adult lymphoma survivors
      attending an out-patients clinic.
AB  - Little is known about the impact of the cancer experience on people following the
      completion of treatment. Work has begun to outline such experiences primarily in
      the United States. The purpose of this study was to explore the 'survival'
      experience within a British context of care, outlining the changes, problems and
      needs expressed by adult cancer survivors. A convenience sample of 10 adult
      lymphoma patients from one large teaching hospital was interviewed a minimum of
      18 months following the completion of successful treatment. Data were collected
      by means of tape-recorded semi-structured interviews, using a schedule based on
      the Cancer Survivorship Questionnaire (Loescher et al., 1990). Data were analysed
      using content analysis and this indicated that, whilst survival itself may be
      reward enough for some, others seek to improve or adjust their current status,
      physically, psychologically or socially. It was concluded that the British cancer
      survivors were affected in many ways, some having to adjust more than others to
      the consequences of cure. The preliminary findings pointed towards a notion of
      'subtle survivorship' in the British survivors. While they reported many changes
      in their lives after treatment, many were typically accepting of these and
      successfully adjusted to their new lives.

PMID- 7711982
TI  - Treatment of depression with flupenthixol in terminally ill patients.
AB  - In recent years, there has been much interest in the psychological well-being of
      cancer patients (Buckberg et al., 1980; Plumb & Holland, 1977; Razavi et al.,
      1990; Grassi et al., 1989). It is recognized that if depression is detected and
      treated, the quality of life for the patient is improved (Holland, 1987;
      Valentine & Saunders, 1989). Many patients are treated with tricyclic anti
      depressants which work well in some cases, but these drugs can have the
      disadvantage of taking 3 weeks before any improvement in the mood of the patient
      is observed. They can also cause unpleasant side-effects, e.g. dry mouth, urinary
      retention and constipation. These symptoms are often already present in the
      terminally ill and their exacerbation can make these drugs unacceptable to such
      patients. Two cases of depression which were detected on admission to a hospice
      and which were successfully treated with flupenthixol dihydrochloride are
      reported.

PMID- 7711983
TI  - The third action plan of the Europe Against Cancer.

PMID- 7711984
TI  - A middle-east oncology experience. Implementation of an oncology nursing
      programme.

PMID- 7711985
TI  - The combination of tizanidine markedly improves the treatment with
      dextromethorphan of heroin addicted outpatients.
AB  - According to the hypothesis implying that the main mechanism underlying opiate
      addiction is the blockade by opiates of NMDA receptor functions and subsequent
      upregulation and supersensitivity of the receptors, noncompetitive NMDA receptor
      blocker dextromethorphan (DM) has been successfully used in the heroin addict
      treatment. As the stimulation of NMDA receptors modulates the release of
      neurotransmitters and hormones such as NE, D, ACh, GH, LH, LSH, ACTH etc., all of
      which have been found responsible for the manifestation of abstinence syndrome
      signs including craving and neuronal death by excessive stimulation of NMDA
      receptors, the incomplete blockade of the NMDA receptors minimizes the intensity
      of the abstinence syndrome and provides the downregulation of the receptors. In
      the present study, tizanidine (TIZ), which inhibits the release of endogenous
      excitatory aminoacids by the agonistic activity on alpha 2-adrenoreceptors, was
      combined with DM to obtain further benefits. Forty-four male and three female
      heroin addicts were the subjects of the study. Their daily mean heroin intake was
      about 2.28 g street heroin. The main duration of heroin use was approximately 3.4
      years. Two to three hours after abrupt withdrawal, the outpatients were given 15
      mg DM every hour, 25 or 50 mg chlorpromazine (CPZ) + 4 mg TIZ every six hours and
      10 mg diazepam + 10 mg hyoscine N-butyl Br + 250 mg dipyrone every six hours
      three hours following CPZ. The addicts were controlled twice a day. Yawning,
      rhinorrhea, perspiration, piloerection, restlessness, insomnia, emesis, diarrhea,
      craving, rejection of smoking and pupils were observed and/or questioned. Two of
      the 47 outpatients took heroin on the first days.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7711986
TI  - Adverse drug reactions (ADRs) in patients with previous history of chronic
      alcohol consumption without signs of chronic hepatic damage. A prospective study.
AB  - An intensive and prospective drug surveillance method was used to monitor 105
      hospitalized patients having a previous history of chronic alcohol consumption
      without signs of hepatic damage at the Dr. Sotero del Rio hospital, Santiago,
      Chile. The aim of the work was to characterize and study the incidence of ADRs
      associated with chronic alcohol addiction in patients hospitalized for different
      pathological conditions. The incidence of ADRs in this group (41.9%) was slightly
      higher than those from other studies carried out in our country in patients
      hospitalized in the internal medicine service from other Chilean hospitals.
      However, alcohol addiction was not considered in these studies. According to
      causality, 58.8% of the ADRs were regarded as probable, 6.9% as definite and
      34.3% as possible. The severity of ADRs was determined as 18.6% mild, 53.9%
      moderate and 27.5% as severe events. These ADRs were manifested in a dose-related
      fashion (80.4%). Furosemide, heparin, and gentamicin were the drugs mainly
      associated with ADRs. The most commonly affected system were metabolic (33.3%),
      renal (19.6%), and gastrointestinal (19.6%). There was a higher incidence of ADRs
      in those patients with longer stay at the hospital, in patients on multiple-drug
      therapy, and in patients with impaired renal function. The frequency of ADRs was
      not related to age, sex, and pattern of alcohol consumption.

PMID- 7711987
TI  - Comparative bioavailability of single doses of tablet formulations of cetirizine
      dihydrochloride in healthy male volunteers.
AB  - The bioavailability of two tablet formulations of cetirizine (Zetir from Abbott
      and Zyrtek from UCB) were compared in 14 healthy male volunteers who received a
      single dose of 10 mg of cetirizine dihydrochloride in an open randomized two
      period crossover design with a 7-day washout period between doses. Plasma samples
      were obtained over a 24 h interval and cetirizine concentrations were determined
      by HPLC with ultraviolet detection. From the plasma cetirizine concentration vs.
      time curves, AUC(0-24) (area under the concentration vs. time curves from 0 to 24
      h), Cmax (maximum achieved concentration), Tmax (time to achieve Cmax), Ke
      (terminal first order elimination constant), elimination half-life (t1/2) and
      AUC(0-infinity) (area under the concentration vs. time curves extrapolated to
      infinity) were obtained. The two cetirizine dihydrochloride tablet brands did not
      show statistically significant differences in bioavailability as assessed by
      analysis of AUC(0-24), AUC(0-infinity), Cmax, Tmax, Ke and t1/2 values. Based on
      these results and on the U.S. Food and Drug Administration requirements [1985,
      1993], we conclude that both formulations are bioequivalent.

PMID- 7711988
TI  - Simvastatin treatment of hypercholesterolemia in patients with insulin dependent
      diabetes mellitus.
AB  - The effects of 16 weeks therapy with the HMG-CoA reductase inhibitor Simvastatin
      10-20 mg (n = 12) was compared to placebo (n = 13) in 25 euthyreoid males with
      insulin dependent diabetes mellitus and fasting total serum cholesterol above 6
      mmol/l. Insulin dependence was defined as a glucagon stimulated C-peptide level
      less than 0.6 mmol/l. The study was placebo-controlled, double-blind with a
      parallel group design. Body weight, blood pressure, glycemic control as well as
      liver enzymes were unchanged and simvastatin was well tolerated by all patients.
      Ophthalmological slitlamp examination before and at the end of the study period
      did not show development of new lenticular opacities. Simvastatin decreased serum
      total cholesterol from 6.7 +/- 1.0 mmol/l (mean +/- SD) to 4.9 +/- 0.4 (p < 0.001
      vs. placebo) and LDL-cholesterol from 4.6 +/- 0.7 mmol/l to 2.8 +/- 0.3 (p <
      0.001 vs. placebo). HDL-cholesterol and triglycerides remained unaltered. A
      positive influence on the atherosclerotic process in patients with insulin
      dependent diabetes mellitus remains, however, to be proven.

PMID- 7711989
TI  - Investigation on antibiotics in a hospital for a one-year period.
AB  - Defined daily dose (DDD) units were used to analyze the antibiotic utilization in
      a University Military Hospital for a one-year period. The data were collected
      from hospital records. The mostly prescribed drug groups were penicillins (broad
      spectrum), systemic sulfonamides and combinations and tetracyclines. Amoxycillin,
      doxycycline and co-trimoxazole were most frequently used. Circannual variations
      were observed only in the utilization of amoxycillin and doxycycline during the
      year.

PMID- 7711990
TI  - Analgesic and urodynamic effects of epidural meperidine and pentazocine--a
      comparative study.
AB  - Meperidine 1 mg kg-1 and pentazocine 0.3 mg kg-1 were administered epidurally to
      investigate their effect on vesical function in twenty American Society of
      Anesthesiologists Classification I (ASA-1) adult males. Cystometry was performed
      before and 45 minutes following epidural administration of meperidine and
      pentazocine. There was no significant change in maximum cystometric capacity,
      detrusor pressure at which detrusor reflex occurred and in vesical compliance
      following epidural administration of meperidine in ten patients and also in ten
      patients who received epidural pentazocine. The mean onset of analgesia after
      epidural administration of meperidine was 8 minutes which lasted for more than
      360 minutes whereas mean onset of analgesia after epidural administration of
      pentazocine was 4 minutes which lasted for more than 360 minutes. There was no
      significant change in heart rate, blood pressure and respiratory rate after
      epidural administration of either meperidine or pentazocine. None of the subjects
      in either of the groups experienced any difficulty in passing urine, frequency or
      urgency of micturition. Side-effects like nausea, vomiting, pruritus and
      respiratory depression were not observed. It is concluded that epidural
      administration of meperidine 1 mg kg-1 or pentazocine 0.3 mg kg-1 produces
      significant analgesia of faster onset without altering vesical function as
      documented, both subjectively by voiding symptoms and objectively by cystometry.

PMID- 7711991
TI  - Diltiazem vs. nicardipine on ambulatory and exercise blood pressure and on
      peripheral hemodynamics.
AB  - The present study was aimed at evaluating the antihypertensive efficacy of
      sustained-release diltiazem 180 mg vs. sustained-release nicardipine 40 mg both
      given twice daily. To this end 20 patients with mild to moderate hypertension
      were studied. After a two-week placebo period diltiazem and nicardipine were
      administered for 4 weeks according to a crossover design. To assess the
      antihypertensive efficacy of the two drugs all patients underwent Twenty-four
      hour non-invasive blood pressure (BP) monitoring and a submaximal bicycle
      ergometric test. Ambulatory BP monitoring showed a tendency for systolic BP to be
      lower with nicardipine than with diltiazem during waking hours, while diastolic
      BP was lowered to the same extent by the two drugs. During sleep a slightly
      greater BP fall was observed with diltiazem. 24-hour spontaneous BP variability
      was slightly reduced with diltiazem and unchanged with nicardipine. Mean 24-hour
      heart rate was also unchanged with nicardipine and slightly reduced with
      diltiazem. Peripheral resistance measured by plethysmography significantly
      decreased with the former but not with the latter. BP and heart rate response to
      exercise was left unchanged by nicardipine and was slightly decreased by
      diltiazem. This study demonstrates that both sustained-release diltiazem and
      nicardipine are effective in controlling BP throughout the 24 hours without
      increasing BP variability. While the antihypertensive action of nicardipine was
      associated with a decrease of peripheral resistance, this was not the case with
      diltiazem.

PMID- 7711992
TI  - Intensified diabetes management: lessons from the diabetes control and
      complications trial.
AB  - The results of the multicenter diabetes control and complications trial are
      examined and methods for the implementation of the findings for individuals with
      type I and type II diabetes are discussed. More than a decade ago the question
      was raised of whether tight glycemic control would prevent or slow the
      progression of microvascular complications. In 1993, having studied 1441
      individuals with type I diabetes randomized to either intensive glycemic control
      (HbA1c < 7%) or conventional glycemic control (HbA1c > 9%), it was concluded that
      a reduction in risk of retinopathy, neuropathy and nephropathy could be realized
      if near normal glycemic control were achieved. Some questions remained, however.
      For example, could intensive treatment be achieved in routine practice under the
      auspices of primary care physicians? Are the findings in this study applicable to
      individuals with type II diabetes? These questions are addressed through the
      introduction of staged diabetes management (SDM), an innovative approach to the
      treatment of diabetes and the prevention of its complications. SDM is designed as
      a data-based systematic approach to diabetes treatment that targets blood glucose
      control. Studied in 40 clinical sites throughout the United States and evaluated
      in 30 sites worldwide, SDM promises to provide appropriate clinical guidance to
      both primary care and specialist physicians seeking to alter current practice
      patterns by adopting a systematic approach to diabetes management.

PMID- 7711993
TI  - Comparative effects of atenolol and clonidine on polygraphically recorded sleep
      in hypertensive men: a randomized, double-blind, crossover study.
AB  - The effects on sleep of atenolol and clonidine were compared in 8 hypertensive
      men (mean age 46.9 years, range 16-56 years) without prior history of sleep
      disturbances. Polygraphic sleep recordings were performed at baseline (NO) and
      after a single oral dose of atenolol (100 mg) or clonidine (0.15 mg) at 6:00 pm
      at a 48-hour interval in a double-blind randomized crossover protocol. Both
      medications lowered arterial pressure to a similar extent. The subjective quality
      of sleep was judged satisfactory after both medications, the number of patients
      reporting dreams decreased from 5 (NO) to 1 after each treatment night. Total
      sleep time decreased slightly but not significantly after atenolol (440 +/- 63
      min vs 474 +/- 47 min at baseline). Sleep latency was not affected after atenolol
      but significantly decreased after clonidine (16.9 +/- 21.6 vs 28.6 +/- 16.6 at
      baseline, p < 0.02). Although rapid-eye movement (REM) sleep time decreased after
      atenolol (71 +/- 30 min vs 95 +/- 30 min at baseline, p < 0.05), the percentage
      of REM sleep was unchanged (22 +/- 7% vs 23 +/- 5%). In contrast, clonidine
      strikingly reduced both REM sleep time (54 +/- 28 min vs 95 +/- 30 min at
      baseline, p < 0.002) and percentage of REM sleep (14 +/- 6% vs 23 +/- 5%, p <
      0.0005). Thus atenolol tends to decrease total sleep time but does not affect the
      normal architecture of sleep, clonidine has a marked hypnotic effect, similar to
      that of some sedative medications and significantly reduces REM sleep.

PMID- 7711994
TI  - Differences in nifedipine concentration-effect relationship between capsule and
      slow release tablet administration.
AB  - The relationships between nifedipine plasma concentrations and its hypotensive
      and positive chronotropic effects were studied in healthy volunteers who received
      either a 10 mg capsule (CAP) or a 20 mg slow release tablet (SRT). Plasma
      concentrations rose more rapidly after CAP than after SRT, Cmax being 131 +/- 39
      and 40 +/- 7 ng/ml and tmax being 0.5 +/- 0.07 and 1.8 +/- 0.4 h, respectively.
      Both formulations produced a reduction in diastolic blood pressure which
      exhibited a significant linear correlation (p < 0.01) with nifedipine plasma
      concentration. However, the slope obtained with SRT was significantly higher than
      that of CAP (0.24 +/- 0.05 vs 0.07 +/- 0.01, p < 0.01). That is, a similar
      hypotensive effect was produced at a lower concentration with SRT than with CAP.
      A positive chronotropic effect which exhibited a highly significant correlation
      with nifedipine plasma concentration (p < 0.0001) was observed with CAP.
      Conversely, with SRT heart rate increase was smaller and there was no significant
      correlation with nifedipine plasma concentration (p > 0.45). Since the measured
      decrease in blood pressure is the outcome of nifedipine-induced vasodilation and
      of homeostatic responses, results are interpreted as follows. Fast nifedipine
      input after CAP induced a brisk change in physiological conditions and hence
      triggered an important homeostatic response, visualized as heart rate increase,
      which partially offset the hypotensive effect. With SRT, there was a gradual
      change in blood pressure producing lesser activation of compensatory mechanisms
      and therefore the hypotensive effect of nifedipine was less antagonized than with
      CAP. Nifedipine SRT does not only exhibit pharmacokinetic advantages, but also a
      more favorable pharmacodynamic profile than CAP.

PMID- 7711995
TI  - Experimental modeling of the effect of uremia on cyclosporin A bioavailability.

PMID- 7711996
TI  - Carcinomatous meningitis: clinical manifestations and management.
AB  - Carcinomatous meningitis (CM) is a cause of significant morbidity and mortality
      in patients with cancer. During the past 15 years, diffuse leptomeningeal
      metastases of extracranial malignant tumors have been increasingly reported
      [Wasserstrom et al. 1982, Theodore and Gendelman 1981, Little et al. 1974, Olson
      et al. 1974, Yaphey et al. 1978, Sorensen et al. 1984], CM is increasing in
      frequency because of improved survival of patients with systemic anti neoplastic
      therapies and increased awareness of this problem among physicians. In this
      review, we will be discussing the epidemiology, etiology, pathology,
      pathophysiology, clinical manifestations, diagnosis and management of
      carcinomatous meningitis, as well as the status of recent basic and clinical
      investigations.

PMID- 7711997
TI  - Statistical tools for understanding variation: the allocation of operating suite
      time.
AB  - Australian hospitals are becoming increasingly familiar with the 'new' tools for
      continuous quality improvement. In particular, many are becoming increasingly
      competent in establishing and supporting quality improvement teams for process
      evaluation and improvement. The main problems with such teams now seems to arise
      in relation to the analysis and interpretation of data on the process. This paper
      provides an example of the types of analyses and interpretations required of
      today's quality improvement practitioner in health care.

PMID- 7711998
TI  - Maintaining quality of aged care in institutions: from structure to outcome.
AB  - Maintenance of quality of care in Australian nursing homes has evolved, being
      initially concerned mainly with physical features of the buildings. Progress
      occurred when regulations were introduced for nursing practices, staff levels and
      procedures generally. In the present phase, the focus has been on outcome in
      terms of the quality of life of the residents. This is being achieved by laying
      down specific outcome standards and their implementation is controlled by an
      inspectorial system that has the capacity to apply sanctions.

PMID- 7711999
TI  - Quality assurance in the management of alcohol withdrawal in a general hospital.
AB  - We have shown previously that a standardized protocol is effective in the
      management of alcohol withdrawal in a general hospital. In this study a Quality
      Assurance (QA) approach was used to determine whether all patients at risk were
      detected and treated correctly in time. A total of 500 episodes were monitored,
      82% of patients at risk were identified, and 89% of patients were seen within 24
      h (median 4 h). The protocol was followed correctly in 86% of cases but was
      inappropriately applied in 7.2%. Medication was given in 242 cases, on 93% of
      occasions according to guidelines. In all, 11.8% of episodes became complicated
      by seizure, hallucinations or confusion and two patients had terminal respiratory
      failure which worsened after sedation. A standardized protocol for alcohol
      withdrawal can be used in a general hospital with high rates of detection of at
      risk patients, a high rate of compliance with treatment guidelines and a low rate
      of complications.

PMID- 7712000
TI  - Reporting of cases of non-accidental injury: a survey of parents' responses.
AB  - Parental responses to the process of referral to statutory bodies because of
      their child's suspected non-accidental injury were obtained using the
      questionnaire method. The results were analysed in terms of their demographic
      details, subsequent social and emotional adjustment together with an evaluation
      of parental perception of the service they received. Parents' reported some
      positive outcomes as a result of the referral, but the majority of responses
      highlighted the need to develop a model of investigation that offers more
      emotional support to parents, giving them more and better information and
      allowing their point of view to be heard and respected.

PMID- 7712001
TI  - The quality management journey: the progress of health facilities in Australia.
AB  - Many facilities in Australia have taken the Total Quality Management (TQM) step.
      The objective of this study was to examine progress of adopted formal quality
      systems in health. Sixty per cent of organizations surveyed have adopted formal
      systems. Of these, Deming adherents are the most common, followed by eclectic
      choices. Only 35% considered the quality transition as reasonably easy. There was
      no relationship between accreditation and formal quality systems identified. The
      most common improvement techniques were: flow charts, histograms, and cause and
      effect diagrams. Quality practitioners are happy to use several tools
      exceptionally well rather than have many tools at their disposal. The greatest
      impediment to the adoption of quality was the lack of top management support.
      This study did not support the view that clinicians are not readily actively
      supporting quality initiatives. Total Quality Management is not a mature concept;
      however, Chief Executive Officers are assured that rewards will be realized over
      time.

PMID- 7712002
TI  - Quality management for a health education unit.
AB  - Specialty health education units are unique in the health care system. Quality
      Assurance (QA) protocols developed for general ward and hospital department use
      are not always able to accommodate the unique organizational and functional
      elements found in such units. In addition, QA measures are all too infrequently
      applied in the area of health education. The Diabetes Centre at the Prince of
      Wales Hospital, Randwick is staffed by a multi-disciplinary team which provides
      in excess of 800 clinical and/or educational occasions of service per month. This
      paper describes the development and implementation of a Quality Management Plan,
      specific to the unit's needs, that was introduced in stages over a number of
      years.

PMID- 7712003
TI  - Receptors for endothelin-1 in asthmatic human peripheral lung.
AB  - [125I]-endothelin-1 ([125I]-ET-1) binding was assessed by autoradiography in
      peripheral airway smooth muscle and alveolar wall tissue in human non-asthmatic
      and asthmatic peripheral lung. Levels of specific binding to these structures
      were similar in both non-asthmatic and asthmatic lung. The use of the receptor
      subtype-selective ligands, BQ-123 (ETA) and sarafotoxin S6c (ETB), demonstrated
      the existence of both ETA and ETB sites in airway smooth muscle and in alveoli.
      In airway smooth muscle from both sources, the great majority of sites were of
      the ETB subtype. Quantitative analyses of asthmatic and non-asthmatic alveolar
      wall tissue demonstrated that 29-32% of specific [125I]-ET-1 binding was to ETA
      sites and 68-71% was to ETB sites. Thus, asthma was not associated with any
      significant alteration in the densities of ETA and ETB receptors in peripheral
      human lung.

PMID- 7712004
TI  - Involvement of B2 receptors in the bradykinin-induced relaxation of guinea-pig
      isolated trachea.
AB  - 1. The aim of this study was to determine the receptor type and involvement of
      arachidonic acid metabolites in bradykinin-induced relaxation of the guinea-pig
      isolated trachea. 2. In the resting tracheal preparation, bradykinin (0.1 nM-30
      microM induced a concentration-related contractile response (pD2 = 8.8 +/- 0.3).
      The maximal tension (1056 +/- 321 mg) was observed at 0.3 microM bradykinin. In
      contrast, when tracheal preparations were pre-contracted with histamine (30
      microM leading to a half-maximum response), a concentration-related relaxation
      was observed with bradykinin. At the highest concentration of bradykinin used (3
      microM), a reversal of 63 +/- 13% of the contractile response to histamine was
      observed. Both effects of bradykinin were inhibited by the cyclo-oxygenase
      inhibitor, indomethacin (1 microM). In concentration-response curves, melittin
      (10 nM-1 microM), a direct activator of phospholipase A2, mimicked both effects
      of bradykinin. The highest concentration of melittin used (1 microM), induced a
      tension of 813 +/- 120 mg and led to the reversal of 41 +/- 8% of the contractile
      response to histamine. The contractile effect of melittin was inhibited in the
      presence of both indomethacin (1 microM) and AA861 (1 microM), a 5-lipoxygenase
      inhibitor. 3. [Des Arg9]-bradykinin (1 nM-3 microM), a B1-receptor agonist, was
      unable to relax precontracted guinea-pig tracheal preparations. The relaxation
      induced by bradykinin was antagonized by the B2 receptor antagonists, Hoe 140 (D
      Arg0[Hyp3,Thi5,D-Tic7,Oic8]bradykinin) and NPC 17761 (D-Arg0[Hyp3,D-HypE(trans
      thiophenyl)7,Oic8]bradykinin ). Hoe 140 (0.1 microM to 0.6 microM) behaved as a
      non-competitive antagonist with an apparent pA2 = 7.2 +/- 0.4, whereas NPC 17761
      (0.3 to 1 microM) competitively antagonized bradykinin-induced relaxation with a
      pKB = 7.3 +/- 0.2. The Schild regression slope did not differ from unity, 0.96 +/
      0.20, P<0.05.4. These data demonstrate that bradykinin-induced relaxation of
      guinea-pig trachea occurs via the activation of bradykinin B2-receptors. The
      stimulation of B2-bradykinin receptors induces the activation of the cyclo
      oxygenase pathway, leading either to contraction or relaxation depending on the
      tone of the trachea.

PMID- 7712005
TI  - Evidence that nitric oxide from the endothelium attenuates inherent tone in
      isolated pulmonary arteries from rats with hypoxic pulmonary hypertension.
AB  - 1. The inherent contractile tone, and its modulation by the endothelium, have
      been studied in isolated pulmonary artery preparations taken from rats in which
      pulmonary hypertension was induced by exposure to a hypoxic environment (10% O2)
      for 14 days. Control rats were housed in room air. 2. All preparations in which
      the endothelium was left intact relaxed in response to acetylcholine (43 +/- 4%
      and 54 +/- 9%, reversal of the noradrenaline-induced contraction in control and
      hypoxic rats, respectively) indicating that the endothelium was functional in
      both groups of rats. 3. Exposure of the preparations to Ca(2+)-free physiological
      salt solution containing 2 mM EGTA for 30-40 min had no effect on preparations
      from control rats but caused relaxation in preparations from hypoxic rats. The
      relaxation (taken as a measure of the inherent tone in the preparations) was
      larger in preparations without endothelium (14.5 +/- 1.9 mN mm-2; n = 5) than in
      preparations with endothelium (9.1 +/- 1.2 mN mm-2; n = 5). 4. In preparations
      from hypoxic rats the magnitudes of the contractions to 80 mM K+ and to
      noradrenaline (0.1 microM) were less than in preparations from control rats. This
      may have been because the preparations from hypoxic rats were already partially
      contracted due to the inherent tone. 5.The nitric oxide (NO) synthase inhibitor,
      NG-nitro-L-arginine methyl ester (L-NAME, 0.1-1 100 microM)had negligible effect
      on preparations from control rats or on endothelium-denuded preparations from
      hypoxic rats, but produced concentration-dependent contractions (maximum
      contraction 7.4 +/- 0.7 mN mm-2 (n = 4) with 100 micro M) in endothelium-intact
      preparations from hypoxic rats. This effect of L-NAME was prevented by L-arginine
      (1 mM) but not by D-arginine (1 mM).6. Contractions to L-NAME were also seen in
      endothelium-intact arteries from control rats if the preparations were first
      partially contracted by exposure to K+, endothelin, U46619 (thromboxane
      mimetic)or noradrenaline.7 It is concluded that isolated pulmonary artery rings
      from hypoxic rats, but not those from control rats, have substantial inherent
      tone. This inherent tone is normally attenuated by the generation of an
      endothelium-derived factor that is probably NO. A stimulus for the release of NO
      from the endothelium may be the contraction of the underlying smooth muscle,
      whether the contraction is inherent in the tissue, as in preparations from
      hypoxic rats, or is induced by a vasoconstrictor spasmogen.

PMID- 7712006
TI  - The kinin B1 receptor antagonist des-Arg9-[Leu8]bradykinin: an antagonist of the
      angiotensin AT1 receptor which also binds to the AT2 receptor.
AB  - 1. Agonists and antagonists of kinin B1 and B2 receptors were evaluated in vitro
      for their effects against angiotensin II (AII)-induced contractile responses in
      the rabbit aorta and for their binding properties to angiotensin AT1 and AT2
      receptors from purified membrane of rat liver and lamb uterus respectively. 2. In
      aortic rings, the kinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin (BK) (3
      100 microM) caused a concentration-dependent decrease in sensitivity and a
      depression of the maximum response to AII. Des-Arg10-[Leu9]kallidin (KD), des
      Arg9-BK, des-Arg10-KD, BK or KD at 3 microM had no effect against AII-induced
      contractions. 3. Des-Arg9-[Leu8]BK (3 or 100 microM) did not affect contractions
      of aortic rings to histamine, potassium chloride, endothelin-1, 5
      hydroxytryptamine, noradrenaline and the thromboxane A2-mimetic, U46619. 4. Des
      Arg9-[Leu8]BK displaced [125I]-Sar1-AII binding to the AT1 subtype in rat liver
      membranes with a Ki value of 1.1 +/- 0.4 microM. Values of Ki for des-Arg9-BK and
      KD were 45 +/- 13 microM and 25 +/- 22 microM, respectively. The other kinin
      derivatives des-Arg10-KD, BK and des-Arg10-[Leu9]KD at concentrations up to 100
      microM did not bind to the AT1 receptor. 5. All the kinin derivatives except BK
      bound to AT2 receptors in lamb uterus membranes. Values of Ki for des-Arg9
      [Leu8]BK, des-Arg10-[Leu9]KD, des-Arg9-BK, des-Arg 10-KD and KD were 0.3 +/- 0.1,
      0.7 +/- 0.1, 1.2 +/- 0.3, 1.5 +/- 0.3 and 7.0 +/- 1.6 microM, respectively. 6. In
      conclusion, des-Arg9-[Leu8]BK is an insurmountable antagonist of AII-induced
      contractions in the rabbit aorta and also binds with a relatively high affinity
      to AT1 and AT2 receptors in isolated membrane fractions. These additional
      properties of des-Arg9-[Leu8]BK should be considered when it is used as an
      antagonist to characterize kinin B1 receptors.

PMID- 7712007
TI  - G-protein involvement in muscarinic receptor-stimulation of inositol phosphates
      in longitudinal smooth muscle from the small intestine of the guinea-pig.
AB  - 1. Aluminium fluoride (AlF), pertussis toxin (PTX) and cholera toxin (ChTX) have
      been used to examine the involvement of G-proteins during muscarinic
      acetylcholine receptor (AChR) stimulation of inositol phospholipid hydrolysis in
      fragments of longitudinal smooth muscle from the small intestine of the guinea
      pig. 2. Carbachol (CCh) induced time- and concentration-dependent increases in
      [3H]-inositol monophosphates, [3H]-inositol (1,4) bisphosphate, [3H]-inositol
      (1,3,4) trisphosphate, [3H]-inositol (1,4,5) trisphosphate ([3H]-Ins (1,4,5)P3)
      and [3H]-inositol tetrakisphosphates measured by h.p.l.c. These increases were
      inhibited > 95% in the presence of the muscarinic AChR antagonist atropine (0.5
      microM). 3. AlF transiently increased the basal levels of [3H]-Ins (1,4,5)P3 but
      increases in the levels of the other [3H]-inositol phosphates occurred more
      slowly. CCh-induced increases in the levels of all the [3H]-inositol phosphates
      were strongly inhibited in the presence of AlF. 4. PTX had no effect on basal
      levels of any of the [3H]-inositol phosphates but reduced the effects of CCh on
      these; ChTX had no effects on either basal or CCh-stimulated levels. 5. It was
      concluded that muscarinic AChR-stimulated increases in the levels of [3H]
      inositol phosphates occur via both a PTX-sensitive G-protein and a PTX
      insensitive mechanism. The actions of AlF may suggest the involvement of an
      inhibitory G-protein in the regulation of muscarinic AChR-stimulated inositol
      phospholipid turnover.

PMID- 7712008
TI  - Significance of nitric oxide in the stimulation of intestinal fluid absorption in
      the rat jejunum in vivo.
AB  - 1. The effects of inhibiting nitric oxide (NO)-synthase on fluid transport,
      mucosal cyclic GMP and cyclic AMP levels and intraluminal prostaglandin E2 (PGE2)
      release were studied in a model of ligated jejunal loops of anaesthetized rats in
      vivo. Experiments were performed under basal conditions as well as under
      conditions, when net fluid secretion was induced by Escherichia coli heat stable
      enterotoxin a (E. coli STa) or PGE2. 2. Intravenous infusion of the NO-synthase
      inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 0.25-50 mg kg-1, 45 min)
      dose-dependently reversed net fluid absorption to net secretion, whereas infusion
      of D-NAME, the inactive enantiomer of L-NAME, in corresponding doses did not
      influence net fluid transport. N omega-nitro-L-arginine (L-NOARG, 25 mg kg-1),
      another NO-synthase inhibitor, also elicited net secretion of fluid. 3. L-NAME
      (25 mg kg-1)-induced net fluid secretion was reversed to net absorption by
      infusion of L-arginine (400 mg kg-1) or sodium nitroprusside (1 mg kg-1) and s.c.
      administration of indomethacin (10 mg kg-1). Hexamethonium (1 mg kg-1, s.c.), a
      ganglionic blocker and granisetron (100 micrograms kg-1, s.c.), a 5-HT3-receptor
      antagonist, did not influence L-NAME-induced net secretion. 4. Net fluid
      secretion induced by intraluminal instillation of E. coli STa (10 units ml-1) was
      enhanced by infusion of L-NAME (25 mg kg-1) and was inhibited by infusion of L
      arginine (400 mg kg-1) and sodium nitroprusside (1 mg kg-1). D-Arginine (400 mg
      kg-1) did not influence E. coli STa-induced fluid secretion. Likewise, net fluid
      secretion induced by i.a. infusion of PGE2 (79 ng ml-1, 30 min) was enhanced by
      infusion of L-NAME and was inhibited by L-arginine and sodium nitroprusside. D
      Arginine(400 mg kg-1) did not influence PGE2-induced fluid secretion.5. PGE2
      levels in intraluminal fluid were not elevated after infusion of L-NAME (25mgkg
      1) compared to controls.6. Mucosal cyclic GMP and cyclic AMP levels after L-NAME
      treatment were not different from control values.7. These results indicate that
      nitric oxide plays an important role in the regulation of intestinal fluid
      transport. The data suggest a nitric oxide-dependent proabsorptive tone in the
      intestine, which possibly involves the enteric nervous system and suppression of
      prostaglandin formation. This proabsorptive tone also may downregulate fluid
      secretion induced by E. coli STa or PGE2.

PMID- 7712009
TI  - Increase in tone and intracellular Ca2+ in rabbit isolated ear artery by platelet
      derived growth factor.
AB  - 1. The effect of platelet-derived growth factor (PDGF-AB) on tone and
      intracellular Ca2+ ([Ca2+]i) was examined in rabbit isolated ear arteries.
      Arteries were mounted in a myograph and loaded with the Ca(2+)-sensitive
      fluorescent indicator, fura-2, for concurrent measurements of isometric force and
      [Ca2+]i. 2. PDGF-AB contracted rabbit ear artery in a concentration-dependent
      manner. PDGF-AB induced tone was associated with a rise in [Ca2+]i. In the
      presence of noradrenaline, PDGF-AB induced a similar rise in [Ca2+]i but
      contraction in response to PDGF-AB in the presence of noradrenaline was increased
      compared with PDGF-AB alone. 3. PDGF-AB-induced rise in [Ca2+]i and tone were
      abolished by removal of extracellular Ca2+ (with addition of BAPTA, a Ca2+
      chelator), and by preincubation with a dihydropyridine calcium channel blocker, (
      )-202,791. Bistyrphostin, a selective inhibitor of tyrosine kinases, also
      inhibited PDGF-AB-induced tone, but had no effect on noradrenaline- or potassium
      induced tone. 4. PDGF-AB contracts rabbit ear artery by increasing Ca2+ entry
      through voltage-operated calcium channels. This effect involves activation of a
      tyrosine kinase.

PMID- 7712010
TI  - Further analysis of the mechanisms underlying the tracheal relaxant action of
      SCA40.
AB  - 1. SCA40 (1nM-10 microM), isoprenaline (1-300 nM) and levcromakalim (100 nM-10
      microM) each produced concentration-dependent suppression of the spontaneous tone
      of guinea-pig isolated trachea. Propranolol (1 microM) markedly (approximately
      150 fold) antagonized isoprenaline but did not antagonize SCA40. The tracheal
      relaxant action of SCA40 was unaffected by suramin (100 microM) or 8-(p)
      sulphophenyltheophylline (8-SPT; 140 microM). 2. An isosmolar, K(+)-rich (80 mM)
      Krebs solution increased tracheal tone, antagonized SCA40 (approximately 60
      fold), antagonized isoprenaline (approximately 20 fold) and very profoundly
      depressed the log concentration-effect curve for levcromakalim. Nifedipine (1
      microM) did not itself modify the relaxant actions of SCA40, isoprenaline or
      levcromakalim. However, nifedipine prevented the rise in tissue tone and the
      antagonism of SCA40 and isoprenaline induced by the K(+)-rich medium. In
      contrast, nifedipine did not prevent the equivalent antagonism of levcromakalim.
      3. Charybdotoxin (100 nM) increased tracheal tone, antagonized SCA40
      (approximately 4 fold) and antagonized isoprenaline (approximately 3 fold).
      Nifedipine (1 microM) prevented the rise in tissue tone and the antagonism of
      SCA40 and isoprenaline induced by charybdotoxin. 4. Quinine (30 microM) caused
      little or no change in tissue tone and did not modify the relaxant action of
      isoprenaline. However, quinine antagonized SCA40 (approximately 2 fold).
      Nifedipine (1 microM) prevented the antagonism of SCA40 induced by quinine. 5.
      Tested on spontaneously-beating guinea-pig isolated atria SCA40 (1 nM-10 microM)
      increased the rate of beating in a concentration-dependent manner. Over the
      concentration-range 1 microM-10 microM, SCA40 also caused an increase in the
      force of atrial contraction. 6. Intracellular electrophysiological recording from
      guinea-pig isolated trachealis showed that the relaxant effects of SCA40 (1 micro
      M) were often accompanied by the suppression of spontaneous electrical slow waves
      but no change in resting membrane potential. When the concentration of SCA40 was
      raised to 10 micro M, its relaxant activity was accompanied both by slow wave
      suppression and by plasmalemmal hyperpolarization.7. SCA40 (10 nM- 100 micro M)
      more potently inhibited the activity of cyclic AMP phosphodiesterase (PDE)than
      that of cyclic GMP PDE derived from homogenates of guinea-pig trachealis.
      Theophylline(1 micro M- 1O mM) also inhibited these enzymes but was less potent
      than SCA40 in each case and did not exhibit selectivity for inhibition of cyclic
      AMP hydrolysis.8. Tested against the activity of the isoenzymes of cyclic
      nucleotide PDE derived from human blood cells and lung tissue, SCA40 proved
      highly potent against the type III isoenzyme. It was markedly less potent against
      the type IV and type V isoenzymes and even less potent against the isoenzymes
      types I and II.9. It is concluded that the tracheal relaxant action of SCA40 (1
      nM- 1 micro M) does not involve the activation of beta-adrenoceptors or P1 or P2
      purinoceptors. Furthermore, this action is unlikely to depend upon the opening of
      BKca channels with consequent cellular hyperpolarization and voltage-dependent
      inhibition of Ca2+ influx. The tracheal relaxant action of SCA40 (up to 1 micro
      M) is more likely to depend upon its selective inhibition of the type III
      isoenzyme of cyclic nucleotide PDE. At concentrations above 1 micro M, SCA40
      exerts more general inhibition of the isoenzymes of cyclic nucleotide PDE and may
      then promote the opening of BKca channels.

PMID- 7712011
TI  - Functional characterization of the adenosine receptor mediating inhibition of
      intestinal secretion.
AB  - 1. Previous studies have shown that the mixed A1/A2 adenosine agonist 5'-N
      ethylcarboxamido-adenosine (NECA) inhibits intestinal fluid secretion which is
      thought to contribute to its antidiarrhoeal effect in the rat. The aim of this
      study was to characterize the adenosine receptor mediating this antisecretory
      effect via functional studies using a range of selective agonists and antagonists
      and by applying the pharmacological criteria of relative agonist and antagonist
      potencies. 2. Adenosine agonists and antagonists were administered i.v. to
      anaesthetized rats. Intestinal secretion was then stimulated by i.a. infusion of
      vasoactive intestinal peptide (VIP, 0.8 microgram min-1) and the net fluid
      transport across the wall of the jejunum was measured by a recirculation
      technique. 3. The rank order of agonist potency to reduce the response to VIP
      was: NECA > N6-cyclopentyladenosine (CPA) > R-N6-(2-phenylisopropyladenosine) (R
      PIA) > S-PIA > chloroadenosine (2-CADO) > 2-phenylaminoadenosine (CV-1808). This
      order best complies with the rank order of agonist potency that represents
      activation of the recently described A2B receptor: NECA > 2-CADO > R-PIA = CHA >
      S-PIA > = CV-1808 > = CGS-21680. The most potent agonists (NECA, CPA and RPIA)
      had ED50 values in the low microgram range. 4. The anitsecretory action of NECA
      (submaximal dose of 40 micrograms kg-1) was antagonized equally (approximately
      50%) by the selective adenosine antagonists 8-cyclopentyl-1,3-dipropylxanthine
      (DPCPX, 0.1 mg kg-1) and 8-phenyltheophylline (8-PT, 0.1 mg kg-1). This
      equipotent activity indicates the presence of an A2 and not an A1 receptor. 5. It
      is suggested that adenosine A2B receptor agonists could be evaluated for
      potential use as antidiarrhoeal drugs.

PMID- 7712012
TI  - Examination of the role of inhibition of cyclic AMP in alpha 2-adrenoceptor
      mediated contractions of the porcine isolated palmar lateral vein.
AB  - 1. We have examined the effect of elevation of cellular adenosine 3':5'-cyclic
      monophosphate (cyclic AMP) on alpha 1- and alpha 2-adrenoceptor-mediated
      contraction of the isolated palmar lateral vein of the pig. Cellular cyclic AMP
      was increased by either inhibition of phosphodiesterase by rolipram, or direct
      activation of adenylyl cyclase by forskolin. 2. Noradrenaline (1 nM-10 microM)
      caused concentration-dependent contractions of the porcine isolated palmar
      lateral vein (pD2 7.32 +/- 0.07, n = 10). The selective alpha 1-adrenoceptor
      antagonist, prazosin (0.1 microM) and the selective alpha 2-adrenoceptor
      antagonist, rauwolscine (1 microM) caused a 10 fold rightward displacement of the
      concentration-response curve and a combination of the two antagonists caused a
      200 fold rightward displacement of the concentration-response curve. The
      selective alpha 2-adrenoceptor agonist, UK-14304, also produced concentration
      dependent contractions of the palmar lateral vein (pD2 7.70 +/- 0.15, n = 5), but
      the maximum response was 55.5 +/- 7.6% (n = 5) of that produced by noradrenaline.
      Prazosin (0.1 microM) failed to affect responses to UK-14304 but rauwolscine, 1
      microM, caused a 200 fold rightward displacement. The estimated pKB value for
      rauwolscine (8.28 +/- 0.19, n = 10) is consistent with inhibition of alpha 2
      adrenoceptors. Thus, the porcine isolated palmar lateral vein has a population of
      alpha 1- and alpha 2-adrenoceptors capable of producing a contraction. 3.
      Rolipram, 10 micro M, and forskolin, 1 micro M, caused a 2-3 fold rightward
      displacement of the noradrenaline concentration-response curve (CRC), but 1,9
      dideoxyforskolin, 1 micro M, a forskolin analogue which does not activate
      adenylyl cyclase, failed to produce a significant inhibition of noradrenaline
      induced contractions. The combination of forskolin (1 micro M) and rolipram (10
      micro M) were additive, producing a 20 fold rightward displacement of the
      noradrenaline CRC.4. Responses to noradrenaline were similarly affected by a
      combination of rolipram (10 micro M) and prazosin (0.1 micro M) (isolation of
      alpha 2-adrenoceptors) and the combination of rolipram (10 micro M) and
      rauwolscine(1 micro M) (isolation of alpha l-adrenoceptors), resulting in a 100
      fold rightward displacement of the noradrenaline CRC. Although forskolin
      inhibited both alpha l- and alpha 2-adrenoceptor-mediated contractions,the
      effects produced were not similar. In particular, noradrenaline, 0.3-3 micro M,
      produced a significant contraction in the presence of forskolin (1 micro M) and
      prazosin (0.1 micro M) (an alpha 2-adrenoceptor-mediated response) but not in the
      presence of forskolin (1 micro M) and rauwolscine (1 micro M) (an alpha l
      adrenoceptor mediated response).5. Five minute exposure to either rolipram (10
      micro M) or forskolin (1 micro M) elevated [3H]-cyclic AMP of the porcine
      isolated palmar lateral vein by approximately 70% and 150-200%, respectively.
      Neither noradrenaline (1 nM- 100 micro M) nor UK-14304 (1 nM- 100 micro M)
      affected basal levels of [3H]-cyclic AMP,but both produced a concentration
      dependent inhibition of forskolin-stimulated [3H]-cyclic AMP accumulation with a
      pKi of 7.43 +/- 0.1 (n = 3) and 7.97 +/- 0.18 (n = 3), respectively. The effect
      of noradrenaline against forskolin-stimulated [3H]-cyclic AMP accumulation was
      reversed by rauwolscine(1 micro M) but not by prazosin (0.1 micro M). In
      contrast, alpha 2-adrenoceptor activation did not affect rolipram induced
      elevation of [3H]-cyclic AMP.6. These findings indicate that M2-adrenoceptor
      contractions of the porcine isolated palmar lateral vein are not produced by
      reduction in cellular cyclic AMP per se. It is proposed that this response
      involves a novel signal transduction mechanism. However, when cellular cyclic AMP
      has been elevated by agents that stimulate adenylyl cyclase, rather than through
      inhibition of phosphodiesterase, the ability of alpha 2-adrenoceptors to inhibit
      cyclic AMP formation may be of functional importance in vascular smooth muscle.

PMID- 7712013
TI  - Contractility of urinary bladder and vas deferens after sensory denervation by
      capsaicin treatment of newborn rats.
AB  - 1. Capsaicin, a selective sensory neurotoxin, was given to newborn rats and at
      the age of 3 months the contractile activity of the urinary bladder detrusor
      muscle and vas deferens evoked by either electrical field stimulation (EFS) or
      exogenous adenosine 5'-triphosphate (ATP) and carbachol (urinary bladder), or ATP
      and noradrenaline (vas deferens) were tested. 2. EFS of the urinary bladder
      evoked contractions which consisted of cholinergic and purinergic components,
      since they could be partially blocked by either the muscarinic cholinoceptor
      antagonist, atropine (0.3 microM) or by desensitization of P2x-purinoceptors with
      alpha,beta-methylene ATP (10 microM). In capsaicin-treated rats, contractions of
      the urinary bladder evoked by EFS were significantly larger than those of control
      (vehicle-treated) animals, and this difference remained after the purinergic
      component of the contractions was blocked by desensitization of P2x-purinoceptors
      with alpha,beta-methylene ATP. However, when the cholinergic component of the
      contractions was blocked with atropine, the difference between the groups at 8 Hz
      and 16 Hz was abolished; EFS caused significantly larger contractions of the
      capsaicin-treated rat bladder only at frequencies of 2 Hz and 4 Hz. 3. EFS evoked
      contractions of the vas deferens consisted of adrenergic and purinergic
      components since they could be partially blocked by either the alpha-adrenoceptor
      antagonist, phentolamine (3 microM) or by alpha,beta-methylene ATP (10 microM).
      The contractions of the vas deferens were significantly larger than in the
      capsaicin-treated rats only at a frequency of 16 Hz. There were no differences
      between vas deferens contractions of the two groups either after desensitization
      of P2X-purinoceptors by alpha,beta-methylene ATP or in the presence of
      phentolamine.4. Contractions of the capsaicin-treated rat urinary bladder evoked
      by exogenous carbachol (0.1-100 microM) were not significantly different from
      those of controls, the pD2 values being 1.78 +/- 0.23 micro M and 1.90 +/- 0.20
      micro M respectively. There was also no significant difference between the groups
      in contractions of the bladder evoked by ATP (10 micro M-3 mM).5. Contractions of
      the vas deferens evoked by either ATP (10 micro M-3 mM) or noradrenaline (1-1000
      micro M) in the capsaicin-treated group showed no significant difference between
      control and capsaicin treated rats.6. In conclusion, the present results indicate
      that chronic capsaicin treatment increases the amplitude of contractions of the
      rat urinary bladder, an effect which preferentially involves the cholinergic
      component of the response; since the response to carbachol is unaffected, the
      change involves prejunctional mechanisms. In contrast, both the purinergic and
      adrenergic components of contraction in the vas deferens are unaffected by
      capsaicin. It is suggested that sensory nerves have a trophic influence on the
      development of parasympathetic nerves in the rat bladder; removal of sensory
      nerves shortly after birth results in an increase mainly in the cholinergic, and
      to a lesser extent purinergic component.

PMID- 7712014
TI  - Endothelin-1 and endothelin-3 regulate differently vasoconstrictor responses of
      smooth muscle of the porcine coronary artery.
AB  - 1. Using front-surface fluorometry of fura-2 and medial strips of the porcine
      coronary artery, we investigated mechanisms by which endothelin-1 (ET-1) and ET-3
      function as vasoconstrictors. 2. In the presence of extracellular Ca2+(1.25 mM),
      ET-1 (10(-10)-10(-7) M) increased cytosolic Ca2+ concentrations ([Ca2+]i) and
      tension, in a concentration-dependent manner. ET-1, at concentrations greater
      than 10(-8) M, induced an abrupt elevation of [Ca2+]i which reached a transient
      peak (the first component, [Ca2+]i-rising phase) and subsequently declined
      ([Ca2+]i-declining phase) to reach a lower sustained phase (the second component,
      steady-state phase), while the tension rose monotonically to reach a peak and
      then slightly and gradually declined. ET-1, at concentrations lower than 10(-8)
      M, induced slowly developing and sustained increases in [Ca2+]i and tension
      ([Ca2+]i-rising phase followed by steady-state phase). All concentrations of ET-1
      increased tension more slowly than [Ca2+]i. 3. In the presence of extracellular
      Ca2+, ET-3 (10(-8)-10(-5) M) induced concentration-dependent increases in [Ca2+]i
      and tension. However, the maximal elevations of [Ca2+]i and tension induced by ET
      3 were substantially smaller than those induced by ET-1, indicating the
      involvement of an ETA receptor subtype. ET-3, at concentrations greater than 6 x
      10(-7) M, caused biphasic slowly developing increases in [Ca2+]i and tension. At
      concentrations lower than 10(-6) M, ET-3 caused monophasic increases in [Ca2+]i
      and tension. At all concentrations of ET-3, the time courses of increases in
      [Ca2+]i and tension were similar. 4. The biphasic increases in [Ca2+]i and
      tension induced by 10-5 M ET-3 and by 1O-7M ET-1 were significantly inhibited by
      pretreatment with 10-5 M of the Ca2+ entry blocker, diltiazem, although the
      inhibition of the first component of ET-l-induced [Ca2+]i increase was partial.5.
      In the absence of extracellular Ca2+, ET-1 induced a concentration-dependent
      transient increase in[Ca2+]i, possibly due to release of Ca2+ from intracellular
      stores, and a sustained contraction. In contrast, ET-3 ( 10-6 M) caused little,
      if any, transient increase in [Ca2+]i and a small sustained contraction.6.
      Temporal changes in the relationships between [Ca2+]i and tension ([Ca2+]1
      tension relationship)during contractions induced by ET-1 and ET-3 were compared
      with the [Ca2+]i-tension relationship of Ca2+-induced contractions (Ca2+
      contractions) obtained by cumulative applications of extracellular Ca2+(0-7.5 mM)
      to tissues depolarized in the presence of 118 mMK+. In the [Ca2+]i-rising phase,
      ET-1 increased tension more slowly than [Ca2+]i, thereby shifting the [Ca2+]i
      tension relation to the right from that for Ca2+-contractions. In the [Ca2+I
      declining and the steady-state phases, ET-1, at concentrations higher than 10-9
      M, produced greater tension development than that expected from a given change
      in[Ca2+ji, resulting in a leftward shift of the [Ca2+]i-tension relation. During
      ET-3-induced contractions,([Ca2+]i-rising, [Ca2+]i-declining and steady-state
      phases), the [Ca2+]i-tension relation was similar to that of Ca2+-contractions.7.
      BQ-123, a selective ETA receptor antagonist, completely inhibited the increases
      in [Ca2+1]i and tension induced by ET-1 and ET-3.8. These results suggest: (1)
      That ET-1 elicits vasoconstriction by increasing [Ca2+]i through the activation
      of Ca2+ influx from the extracellular space and Ca2+ release from intracellular
      storage sites,and by increasing the Ca2+ sensitivity of the contractile
      apparatus, whereas ET-3 induces vasoconstriction by increasing [Ca2+1] mainly
      through Ca2+ influx from the extracellular space. (2) Distinct mechanisms of time
      dependent modulation of the Ca2+ sensitivity function in the vasoconstrictor
      responses to ET-1 and ET-3. (3) That both ET-1- and ET-3-induced contractions
      seem to be mediated via ETA-receptors in porcine coronary artery, and that the
      ETA-receptor-mediated effects of ET-1 and ET-3 can be dissociated at the sub
      receptor levels of the signal transduction pathway.

PMID- 7712015
TI  - Pharmacology of stretch-activated K channels in Lymnaea neurones.
AB  - 1. Single-channel recording was used to describe the pharmacology of stretch
      activated K channels in Lymnaea neurones using channel blockers amiloride,
      tetraethylammonium (TEA), quinidine, gadolinium (Gd) and diltiazem. 2. Amiloride,
      TEA and quinidine applied to the outside face of the membrane all produced a fast
      flickery block of stretch-activated K channels. All of these agents were without
      effect when applied at the inside face at concentrations as high as 10, 200 and
      10 mM respectively. Neither Gd nor diltiazem had any effect on stretch-activated
      K channels extracellularly (100 microM). 3. Amiloride, TEA and quinidine block
      were voltage-independent with IC50 values at positive (and negative membrane
      potentials of 2.3 (and 2.0) mM, 48 (and 54) mM and 0.8 (and 0.7) mM respectively.
      Woodhull plots for TEA and quinidine block confirmed the voltage independence of
      stretch-activated K channel block by these agents. 4. Hill plots of the amilorde,
      TEA and quinidine block yield Hill coefficients at positive (and negative)
      membrane potentials of 1.7 (and 1.5), 1.4 (and 1.2) and 1.5 (and 1.6 mM)
      respectively. 5. Ethanol (3%) had no apparent effect on stretch-activated K
      channel kinetics or conductance yet reduced the efficacy of quinidine block. 6.
      The above pharmacological fingerprint of the stretch-activated K channel is
      discussed with reference to other K-selective and stretch-activated channels.

PMID- 7712016
TI  - Effects of macrophage depletion on the induction of histidine decarboxylase by
      lipopolysaccharide, interleukin 1 and tumour necrosis factor.
AB  - 1. Our previous work has shown that injection into mice of lipopolysaccharide
      (LPS) and the cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF)
      induces histidine decarboxylase (HDC), the enzyme forming histamine, in various
      tissues such as liver, lung, spleen and bone marrow, but not in the blood. The
      induction of HDC also occurs in nude mice and mast cell-deficient mice. On the
      other hand, haematopoietic cytokines such as IL-3, granulocyte colony-stimulating
      factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) only induce HDC in the
      haematopoietic organs, i.e. bone marrow and spleen. In the present study, the
      effect of macrophage depletion on the induction of HDC was examined. 2. On day 1
      after a single intravenous injection of a macrophage depletor (liposomes
      encapsulating dichloromethylene diphosphonate, which is toxic when ingested into
      macrophages), macrophages were almost completely depleted in the liver and
      reduced by about 50% in the spleen and bone marrow, but not significantly
      affected in the lung. On day 3, the degrees of the depletion were similar to
      those of day 1. In the spleen, macrophages were depleted in the red pulp, and
      there was a structural destruction. 3. In macrophage-depleted mice, the induction
      of HDC by LPS, IL-1 alpha or TNF-alpha was not impaired in the liver, and was
      potentiated in the lung and bone marrow. The induction of HDC was decreased only
      in the spleen at day 3. 4. HDC was not induced by LPS in the spleen of the adult
      rat, which is correspondingly inactive in haematopoiesis.5 These results indicate
      that the major cells in which HDC activity is induced in response to LPS, IL-1
      and TNF are not circulating granulocytes, circulating monocytes, T cells derived
      from thymus, mast cells or phagocytic macrophages. Based on these results, we
      discuss the possibility that the major cells in which HDC was induced in non
      haematopoietic and haematopoietic organs were endothelial cells and
      haematopoietic precursor cells respectively.

PMID- 7712017
TI  - Electrophysiological effects of Ro 22-9194, a new antiarrhythmic agent, on guinea
      pig ventricular cells.
AB  - 1. Cardiac effects of Ro 22-9194 were examined in papillary muscles and single
      ventricular myocytes isolated from guinea-pigs and compared with those of
      moricizine. 2. In papillary muscles, both Ro 22-9194 (> or = 10 microM) and
      moricizine (> or = 1 microM) caused a significant dose-dependent decrease in the
      maximum upstroke velocity (Vmax) and a shortening of the action potential
      duration. 3. In the presence of either drug, trains of stimuli at rates > or =
      0.2 Hz led to an exponential decline in Vmax. This use-dependent block was
      enhanced at higher stimulation frequencies. A time constant (tau R) for Vmax
      recovery from the use-dependent block was 9.3 s for Ro 22-9194 and 26.4 s for
      moricizine. 4. The curves relating membrane potential and Vmax in single myocytes
      were shifted by Ro 22-9194 (30 microM) or by moricizine (3 microM) in a
      hyperpolarizing direction by 8.4 mV and 8.0 mV respectively. 5. In myocytes
      treated with Ro 22-9194 (30 microM), a 10 ms conditioning clamp to 0 mV caused a
      significant decrease in Vmax of the subsequent test action potential; further
      prolongation of the clamp pulse duration resulted in a modest enhancement of the
      Vmax inhibition. In the presence of moricizine (3 microM), a similar conditioning
      clamp > 200 ms caused a significant Vmax reduction; the longer the clamp pulse
      duration, the greater the Vmax reduction. 6. Ro 22-9194 > or = 30 microM caused a
      slight decrease of calcium inward current (ICa) of myocytes without affecting the
      delayed rectifier potassium current (IK). 7. These findings suggest that the
      primary electrophysiological effect of Ro 22-9194 as an antiarrhythmicagent is,
      like moricizine, a use- and voltage-dependent inhibition of sodium channels. From
      the onset and offset kinetics of the use-dependent block, Ro 22-9194 belongs to
      the intermediate kinetic Class I drugs, while moricizine is a slow kinetic drug.
      From the state-dependence of sodium channel block, Ro 22-9194 may belong to
      activated channel blockers, while moricizine belongs to inactivated channel
      blockers.

PMID- 7712018
TI  - Vascular pharmacology of methylene blue in vitro and in vivo: a comparison with
      NG-nitro-L-arginine and diphenyleneiodonium.
AB  - 1. The vascular effects of the soluble guanylyl cyclase inhibitor, methylene blue
      as well as the nitric oxide (NO) synthase inhibitors, NG-nitro-L-arginine (L
      NOARG) and diphenyleneiodonium (DPI) were studied in rat isolated aortic rings
      and conscious, unrestrained rats. 2. Acetylcholine (ACh) and sodium nitroprusside
      (SNP) caused concentration-dependent relaxation of preconstricted aortic rings.
      Both methylene blue (1 x 10(-5) M) and L-NOARG (3 x 10(-5) M) abolished ACh
      induced relaxation; however, methylene blue but not L-NOARG shifted the
      concentration-response curve of SNP to the right. 3. In conscious rats, i.v.
      infusion of methylene blue (1.1 x 10(-5) mol kg-1 min-1), at a concentration
      which reduced the aortic tissue level of cyclic GMP by 50%, did not significantly
      alter mean arterial pressure (MAP) and heart rate (HR). In contrast, i.v. bolus
      injection of L-NOARG (1.5 x 10(-4) mol kg-1) markedly increased MAP and decreased
      HR. 4. Both ACh and SNP dose-dependently decreased MAP in conscious rats.
      Methylene blue did not alter the magnitude or duration of ACh- or SNP-induced
      depressor responses. L-NOARG, on the other hand, significantly though
      incompletely, reduced the magnitude and duration of the depressor response to ACh
      but not SNP. The depressor response to ACh or SNP was not altered by pretreatment
      with indomethacin (1.4 x 10(-5) mol kg-1) or capsaicin (3.3 x 10(-4) mol kg-1).
      5. NG-nitro-L-arginine methyl ester (L-NAME) also caused dose-dependent increases
      in MAP in conscious rats. Both methylene blue and DPI (1 x 10-5 mol kg-1)
      selectively shifted the dose-pressor response curve of L-NAME to the right.6.
      These results suggest that: (1) the inhibition of endogenous NO biosynthesis does
      not necessarily lead to pressor response in vivo, (2) L-NOARG may not produce
      pressor response solely via the inhibition of endogenous endothelial NO
      biosynthesis, and (3) the depressor responses to ACh and SNP may not involve the
      release of NO or prostanoids or afferent nerve transmitters.

PMID- 7712019
TI  - Mechanisms of pulmonary vasoconstriction and bronchoconstriction produced by PAF
      in the guinea-pig: role of platelets and cyclo-oxygenase metabolites.
AB  - 1. The mechanisms of action of platelet activating factor (PAF) in the bronchial
      and cardiovascular systems have not yet been fully elucidated. In order to
      characterize better and to ascertain whether the effects of PAF in both these
      systems may be ascribed to the same mechanisms, we examined the actions of PAF in
      the heart-lung preparation of guinea-pig (HLP). The role of platelets and of
      cyclo-oxygenase metabolites was investigated. 2. In HLPs perfused with autologous
      blood, bolus injections of PAF (4-32 ng) produced major effects at the pulmonary
      vascular and bronchial levels. Both dose-related pulmonary vascular hypertension
      and bronchoconstriction produced by PAF were diminished to the same extent (46%
      and, respectively, 47%) when HLPs were perfused with a medium consisting of
      homologous red blood cells suspended in physiological solution containing 3.5%
      dextran (RBC). This suggests that the effects of PAF partially depend on the
      presence of formed elements. 3. When indomethacin (30 microM) was added to the
      perfusing blood, the dose-response curve for the pulmonary hypertensive responses
      produced by PAF was strongly reduced (90%) in comparison to control preparations,
      whereas the bronchoconstrictor effects of PAF were only partially diminished
      (23%). These data constitute direct evidence that products of the cyclo-oxygenase
      pathway exert a major role in the vascular, rather than in the bronchial actions
      of PAF. 4. In HLPs perfused with RBC containing indomethacin (30 microM), the
      pulmonary vascular hypertensive responses produced by PAF were almost completely
      abolished, thus indicating that cyclo-oxygenase products from tissues are
      involved in these effects. Conversely, PAF administration continued to cause dose
      related bronchoconstrictor responses that were reduced only partially in
      comparison with HLPs perfused with RBC in the absence of the cyclo-oxygenase
      inhibitor. This implies that PAF also has direct action on the
      bronchoconstriction evoked.5. At the cardiac level, administration of PAF in HLPs
      perfused with blood caused a dose-related increase in right atrial pressure
      accompanied by a decrease in left atrial pressure and cardiac output,which were
      completely suppressed or attenuated by the absence of formed elements and the
      addition of indomethacin. This suggests that the progressive heart impairment is
      secondary to the severe pulmonary hypertension induced by PAF.6. The results of
      this study performed in the heart-lung preparation of the guinea-pig, which made
      it possible to simultaneously record cardiovascular and bronchial parameters,
      indicate that various components are involved in the responses produced by PAF.
      It is suggested that different mechanisms depending on the relative contribution
      of these components may account for the PAF-induced effects at the pulmonary
      vascular and airway levels.

PMID- 7712020
TI  - Pharmacology of the octopamine receptor from locust central nervous tissue
      (OAR3).
AB  - 1. The present study characterized highly effective agonists from different
      classes of compounds for the neuronal octopamine receptor (OAR3) of the migratory
      locust (Locusta migratoria L.). Biogenic amines and phenyliminoimidazolidines
      (PIIs) were employed for the study of structure-activity relationships. 2. The
      highest affinity PIIs were predominantly those with substitutions at the
      positions 2 and 4 of the phenolic ring (e.g. NC 7, KI = 0.3 nM, NC 8, KI = 0.81
      nM). Substitutions at these positions always had positive effects on the affinity
      of the respective agonists. 3. Substitutions at the positions 3, 5 and 6,
      however, always had negative effects on the affinity. At the position one of the
      phenolic ring, heterocyclic substituents are preferred. 4. Some PIIs had a more
      than 30 times higher affinity for OARs than for alpha-adrenoceptors which are the
      vertebrate homologues of the insect octopamine receptors. 5. The only non-PII
      with subnanomolar affinity was the aminooxazoline derivative AC 6 (KI = 0.92 nM).
      6. A variety of substances with known insecticidal activity such as
      chlordimeform, demethylchlor-dimeform, amitraz or AC 6 had high affinity for the
      locust neuronal octopamine receptor.

PMID- 7712021
TI  - The receptor occupation and plasma concentration of NKY-722, a water-soluble
      dihydropyridine-type calcium antagonist, in spontaneously hypertensive rats.
AB  - 1. The occupation in vivo by NKY-722 of 1,4-dihydropyridine (DHP) calcium
      antagonist receptors in myocardium, aorta and cerebral cortex was investigated.
      At 1 and 3 h after oral administration of NKY-722 (3 mg kg-1) in spontaneously
      hypertensive rats (SHR), there was a significant (44 and 41%, respectively)
      decrease in the number of myocardial (+)-[3H]-PN 200-110 binding sites (Bmax)
      compared to control values. A greater reduction of Bmax values was observed at 1
      (86%), 3 (88%), 6 (63%) and 12 (46%) h later by a higher dose (10 mg kg-1) of
      this drug. The occupation of myocardial 1,4-DHP calcium antagonist receptors
      after oral administration of NKY-722 correlated significantly with its plasma
      concentration. There was a significant decrease in cerebral cortical (+)-[3H]-PN
      200-110 binding (Bmax) at 1 and 3 h after oral administration of NKY-722 (10 mg
      kg-1). 2. Oral administration of nicardipine (10 mg kg-1) in SHR caused a
      significant reduction of Bmax values for (+)-[3H]-PN 200-110 binding in
      myocardium at 1 and 3 h later and in cerebral cortex at 1 h later. 3. The in vivo
      specific binding of (+)-[3H]-PN 200-110 in particulate fractions of aorta of SHR
      was significantly (79 and 83%, respectively) reduced at 1 and 6 h after oral
      administration of NKY-722 (3 mg kg-1), while myocardial (+)-[3H]-PN 200-110
      binding was decreased by 52% only at 1 h later. Also, nicardipine administration
      reduced in vivo ( + )-[3H]-PN 200-110 binding in aorta at 1 and 6 h later and in
      myocardium at 1 h later. On the other hand, the administration of both NKY-722
      and nicardipine had no significant effect on in vivo (+ )-[3H]-PN 200-110 binding
      in cerebreal cortex.4 It is concluded that NKY-722 may exert more selective and
      sustained occupation in vivo of 1,4-DHP calcium antagonist receptors in vascular
      tissues of SHR than in myocardial and brain tissues.

PMID- 7712022
TI  - Inotropic changes induced by fluoroaluminates in rabbit left atrial muscles:
      possible involvement of G proteins.
AB  - 1. The effects of fluoroaluminate complexes (NaF plus AlCl3) on force of
      contraction, cyclic AMP accumulation and phosphoinositide hydrolysis were
      examined in rabbit left atrial muscles. 2. Fluoroaluminates (1-10 mM NaF + 10
      microM AlCl3) produced a biphasic inotropic response which was composed of an
      early small decline and subsequent increase in force of contraction. In the
      presence of the Al3+ chelator, deferoxamine (100 microM), the positive inotropic
      response was completely abolished and a sustained negative inotropic response
      appeared, suggesting that only the positive inotropic response is due to the
      action of fluoroaluminates. 3. The positive inotropic effect of fluoroaluminates
      was associated with a significant increase in the total duration of a single
      contraction; the time to peak tension and relaxation time were prolonged. In
      contrast, these parameters were substantially abbreviated by isoprenaline or
      histamine. 4. When force of contraction was increased by isoprenaline or
      histamine, the addition of fluoroaluminates caused a marked negative inotropic
      effect, which was eliminated by pretreatment with pertussis toxin. 5.
      Fluoroaluminates did not cause a significant increase in cyclic AMP content at
      concentrations of NaF in the range of 1-10 mM. However, the content of cyclic AMP
      was greatly elevated by fluoroaluminates when the atrial muscles were pretreated
      with pertussis toxin. 6. Accumulation of [3H]-inositol monophosphate in atrial
      muscle strips prelabelled with myo-[3H]-inositol was significantly increased by
      fluoroaluminates at concentrations of NaF over 1 mM. The phosphoinositide
      response to fluoroaluminates remained unchanged with pertussis toxin
      pretreatment. 7.These results indicate that, in rabbit left atrial muscles,
      fluoroaluminates produce a positive inotropic effect which may be mediated by Gq
      but not by Gs proteins; they produce a negative inotropic effect possibly through
      Gi only when Gs is activated with other agents.

PMID- 7712023
TI  - Effect of R56865 on cardiac sarcoplasmic reticulum function and its role as an
      antagonist of digoxin at the sarcoplasmic reticulum calcium release channel.
AB  - 1. The effect of R56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl]-N-methyl
      2- benzothiazolamine) on cardiac sarcoplasmic reticulum (SR) Ca(2+)-release
      channel function was investigated. The effect of R56865 on [3H]-ryanodine and
      [3H]-digoxin binding to SR vesicles and its effect on the ATP-stimulated 45Ca2+
      uptake into SR vesicles was also studied. 2. R56865 (0.5-50 microM) had no effect
      on single-channel open probability (Po) when added to native cardiac SR Ca(2+)
      release channels, incorporated into planar phospholipid bilayers, that had
      previously been activated by 10 microM Ca2+. The single-channel conductance (93
      pS) and the Ca2+/Tris+ permeability ratio (12.5) were also unaffected by R56865.
      3. R56865 failed to affect the rapid Ca(2+)-induced efflux of 45Ca2+ from cardiac
      SR vesicles. The initial efflux rate at an extravesicular [Ca2+] of 0.1 microM
      was 176 +/- 33 nmol 45Ca2+ mg-1 protein s-1 (n = 5). Addition of 0.5-50 microM
      R56865 to the efflux solution did not affect the initial efflux rate or the total
      amount of 45Ca2+ released from the vesicles. 4. The specific binding of [3H]
      ryanodine to SR vesicles can be viewed as a marker for SR Ca(2+)-release channel
      activation. R56865 (0.05-50 microM) did not change the amount of specific [3H]
      ryanodine bound at 10 microM activating Ca2+. Taken together these data (points
      2, 3 and 4) suggest that R56865 does not affect the Ca2+ activation of the
      cardiac SR Ca(2+)-release channel. 5. R56865 (0.5-50 microM) decreased the ATP
      stimulated uptake of 45Ca2+ into cardiac SR vesicles. The total amount of 45Ca2+
      taken up into the vesicles was decreased by 26-37% and the initial rate of uptake
      was also reduced.6. R56865 decreased the binding of [3H]-digoxin to cardiac SR
      vesicles. It inhibited binding of[3H]-digoxin to both sites on SR membranes.
      However, it acted as a mixed type of non-competitive antagonist, as it increased
      the Kd and reduced the Bmax for [3H]-digoxin. Additionally, when SRCa2+-release
      channels incorporated into bilayers were activated by 1 nM digoxin at 10 micro M
      Ca2+, 5 microMR56865 decreased single-channel Po to that seen prior to activation
      by digoxin, confirming that R56865is an antagonist at the cardiac glycoside
      receptor site on the cardiac SR Ca2+-release channel.7. The results presented
      here show that R56865 decreases 45Ca2+ uptake into SR vesicles and also non
      competitively decreases the binding of cardiac glycosides to their activation
      sites on the SRCa2+-release channel. Since this compound fails to affect other
      aspects of the functioning of the SR, we conclude that inhibition of Ca2+-uptake
      into the SR and/or antagonism of digoxin binding to its high affinity sites on
      the cardiac SR Ca2+-release channel may contribute to the protection against
      glycoside induced toxicity seen with R56865. Indeed the reduction of Ca2+ uptake
      into the SR during Ca2+overload may contribute to the protective action of R56865
      against arrhythmias induced by veratridine or by ischaemia. Notwithstanding this,
      it is possible that the multitude of other actions on specific ion translocation
      processes, as well as the possible non-specific membrane effects of R56865, may
      be as responsible for the protection against arrhythmias as the effects on SR
      function we have documented here. However, the simultaneous interference with
      more than one of these processes by R56865 may be required for its anti
      arrhythmic action.

PMID- 7712024
TI  - Inhibition of calcium release from the sarcoplasmic reticulum of rabbit aorta by
      hydralazine.
AB  - 1. The mechanism of hydralazine-induced vasorelaxation was investigated in rabbit
      isolated aorta, by determining its ability to interfere with force development
      under a variety of conditions. 2. Hydralazine relaxed phenylephrine-contracted
      aorta with half maximal relaxation at 17 microM and maximal relaxation above 100
      microM. At 200 microM, hydralazine had little effect on contractions induced by
      25 mM or 50 mM K+. 3. Hydralazine was equally effective at inhibiting contractile
      responses to phenylephrine in the absence or presence of extracellular Ca2+.
      Responses to phenylephrine in Ca(2+)-free solution were blocked to the same
      degree whether hydralazine was applied during filling of the sarcoplasmic
      reticulum (SR) Ca2+ stores or after filling was complete. Caffeine-induced
      contractions were less sensitive to block by hydralazine. 4. Thapsigargin,
      cyclopiazonic acid, ryanodine, nifedipine and diltiazem all failed to block the
      inhibitory effect of hydralazine on tonic contractions to phenylephrine in the
      presence of extracellular Ca2+. However, when cyclopiazonic acid was applied
      either with diltiazem or ryanodine, substantial inhibition of the hydralazine
      response was observed. 5. We propose that tonic contractions to phenylephrine are
      largely maintained by Ca2+ cycling through the SR, with Ca2+ entering the smooth
      muscle cell being sequestered by the SR eventually to leak out through IP3
      activated channels close to the contractile proteins. Sequestration of Ca2+ would
      employ two pathways, one sensitive to inhibitors of the SR Ca(2+)-ATPase and the
      other to Ca antagonists. We further suggest that, in the presence of
      extracellular Ca2+ and phenylephrine, the leakage of Ca2+through IP3-activated
      channels is significantly reduced only if both routes for SR Ca2+ accumulation
      are blocked or the Ca2+-ATPase is blocked while the SR is made leaky with
      ryanodine.6. We conclude that the main action of hydralazine is to block the IP3
      dependent release of Ca2+ from the sarcoplasmic reticulum. Thus conditions that
      diminish the contribution of IP3-induced Ca2+ release to tension can inhibit the
      hydralazine-induced vasorelaxation.

PMID- 7712025
TI  - Evidence for the presence of both pre- and postjunctional P2-purinoceptor
      subtypes in human isolated urinary bladder.
AB  - 1. In order to characterize P2-purinoceptor(s) in human urinary bladder the
      contractile effects of ATP and its slowly-hydrolyzable analogues alpha, beta
      methylene ATP (alpha, beta-MeATP) and beta, gamma-methylene ATP (beta, gamma
      MeATP) were investigated on human detrusor strips taken from patients undergoing
      cystectomy for bladder carcinoma. 2. Serial concentration-response curves (SCRC)
      for ATP, alpha, beta-MeATP and beta, gamma-MeATP were constructed with an
      interval of 25 min between two successive doses to avoid tachyphylaxis. ATP (10
      microM-10 mM) induced a phasic contraction, which was very rapid in onset. The
      dose-response curve to ATP appeared not to be monophasic: at the lower
      concentrations (10-300 microM) the curve was shallow, whilst at high
      concentrations (1-10 mM) the curve was steeper. The magnitude of the response
      obtained at the highest concentration tested (10 mM) was only 21.1 +/- 2.8% (mean
      +/- s.e. mean; n = 4) of the KCl (100 mM)-induced contraction. 3. alpha, beta
      MeATP (0.3 microM-1 mM) and beta, gamma-MeATP (10 microM-1 mM) elicited a phasic
      contraction with a time course similar to that exhibited by ATP. The magnitude of
      the response obtained at the highest concentration tested (1 mM) was 70.3 +/-
      6.3% for alpha, beta-MeATP (n = 10) and 27.9 +/- 4.5% for beta, gamma-MeATP (n =
      8) of KCl (100 mM)-induced contraction. The rank order of potency was alpha, beta
      MeATP > beta, gamma-MeATP > ATP. A plateau of response could not be achieved by
      any of these agonists. 4. The P2-purinoceptor antagonist, suramin (10-300
      microM), dose-dependently antagonized only the lower part of alpha,beta-MeATP
      dose-response curve. Data were analysed in terms of dose-ratio estimated at two
      levels of response (10% and 35% of KC1 100 mM-induced contraction). At 10% of KCl
      response the Schild plot slope was 0.98 and the estimated pKB was 5.85, whereas
      using the dose-ratio at the 35% level of the KCl response, the Schild plot was
      not linear suggesting an interaction of alpha,beta-MeATP with a heterogeneous
      receptor population.5. The putative P2-purinoceptor antagonist, Coomassie
      Brilliant Blue G (CB-G) at 0.3 and 1 l micro M(n = 5), shifted to the left the
      alpha,beta-MeATP SCRC. The response at the highest concentration of agonist was
      potentiated, being equal to 78.8 +/- 11.7% of the KCl (100 mM) response (n = 5).
      CB-G at 0.3 microM also shifted to the left the beta,upsilon-MeATP SCRC and
      significantly potentiated the response at 1 mM up to 46.3 +/- 5.6% of KCl 100 mM
      response (n = 4).6. Pretreatment with terodotoxin (TTX) at 1 microM shifted to
      the left the alpha,beta-MeATP SCRC but the response to the highest concentration
      of the agonist was not potentiated, being 73.6 +/- 9.9% of the KCl(100 mM)
      response (n = 5). TTX (1 micro M) shifted to the left the beta,upsilon-MeATP SCRC
      and significantly potentiated the response at 1 mM (61.6 +/- 3.1% of KCl
      response; n = 4).7. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L
      NAME) at 100 micro M did not modify the SCRC to either alpha, beta or
      beta,upsilon-MeATP.8. We conclude that in human detrusor muscle there is a
      heterogeneity of purinoceptors. The complex antagonism exhibited by suramin
      suggests the presence not only of Ph-purinoceptors but also of another
      contractile P2-purinoceptor subtype insensitive to suramin. Moreover, the
      activity of CB-G and TTX seems to support the existence of a prejunctional P2
      purinoceptor subtype inducing the release of one or more inhibitor
      neurotransmitters.

PMID- 7712026
TI  - Potentiation by tumour necrosis factor-alpha of calcium signals induced by
      bradykinin and carbachol in human tracheal smooth muscle cells.
AB  - The effect of tumour necrosis factor-alpha (TNF alpha) on the increase in
      cytosolic free calcium ([Ca2+])i induced by carbachol and bradykinin (BK) was
      investigated in human tracheal smooth muscle cells in culture (TSMC). BK (10(-12)
      10(-9) M) and carbachol (10(-7)-10(-3) M) produced a concentration-dependent
      increase in [Ca2+]i (pD2 = 10.73 +/- 0.05 and 5.57 +/- 0.03 respectively). The
      increase in [Ca2+]i was significantly enhanced for both agonists in TNF alpha
      treated cells (10 ng ml-1 for 24 h). However, pD2 values were not modified (10.78
      +/- 0.03 and 5.62 +/- 0.04 for BK and carbachol, respectively) suggesting that no
      change in the apparent receptor affinity occurred. Thus, TNF alpha induced
      alterations in Ca2+ homeostasis in human TSMC may be a key mechanism underlying
      airway hyperreactivity.

PMID- 7712027
TI  - Responses of the aorta of the garter snake (Thamnophis sirtalis parietalis) to
      purines.
AB  - 1. Isolated aortic rings from the garter snake (Thamnophis sirtalis parietalis)
      were investigated in order to identify and classify responses to adenosine and
      adenosine 5'-triphosphate (ATP) and their analogues as part of a comparative
      study of vertebrate purinoceptors. 2. Adenosine, D-5'-(N-ethylcarboxamide)
      adenosine (NECA), R- and S-N6-(2-phenylisopropyl) adenosine (R- and S-PIA) and 2
      chloroadenosine (2-CA) all concentration-dependently relaxed aorta preconstricted
      with noradrenaline (NA). The order of potency was: NECA > R-PIA = 2-CA >
      adenosine > S-PIA. Individual pD2 values for the analogues were: NECA 7.12 +/-
      0.13 (9), R-PIA 5.93 +/- 0.25 (7), 2-CA 5.64 +/- 0.40 (5), adenosine 5.04 +/-
      0.10 (13) and S-PIA 4.26 +/- 0.10 (7). The order of potency has characteristics
      of both A1 and A2 receptors and cannot satisfactorily be classified according to
      the P1-(adenosine) purinoceptor subtypes established in mammalian preparations.
      3. ATP, alpha, beta-methylene ATP (alpha, beta-MeATP), 2-methylthio ATP
      (2MeSATP), beta, gamma-methylene ATP (beta, gamma,-MeATP) and uridine 5'
      triphosphate (UTP) all concentration-dependently constricted the isolated aorta.
      The order of potency was alpha, beta-MeATP = 2MeSATP > ATP > beta, gamma-MeATP >
      UTP. Only ATP, alpha, beta-MeATP and 2MeSATP consistently produced a maximum
      response; pD2 values were: ATP 3.98 +/- 0.07 (10), alpha, beta-MeATP 5.86 +/-
      0.15 (12) and 2MeSATP 6.06 +/- 0.23 (9). In vessels preconstricted with NA
      neither ATP nor 2MeSATP caused relaxation in the presence or absence of the
      endothelium. 4. Suramin (0.1 mM) inhibited vasoconstriction to ATP, alpha,beta
      MeATP, 2MeSATP and beta,upsilon-MeATP;however, since contractions to ATP and
      analogues did not reach a maximum response in the presence of this and other
      antagonists, pD2 values could not be calculated.5. Pyridoxalphosphate-6-azophenyl
      2',4'-disulphonic acid (PPADS; 30 micro M), a P2x-purinoceptor
      antagonist,antagonized constrictions to alpha, beta-MeATP only. Reactive blue 2
      (RB2; 30 micro M), a P2Y-purinoceptor antagonist, inhibited vasoconstrictions to
      2MeSATP only.6. Indomethacin (30 micro M) inhibited vasoconstriction in response
      to ATP and 2MeSATP, but not alpha,beta,-MeATP, suggesting that the presence of an
      unaltered phosphate chain on the ATP analogue was necessary to stimulate the
      production of a prostanoid.7. Repeated administration of alpha,beta-MeATP (3
      microM) caused desensitization of the receptor responsible for the constriction
      due to alpha,beta-MeATP whereas the responses to ATP and 2MeSATP were
      unaltered.8. In summary, both P1-purinoceptors mediating vasodilatation and P2
      purinoceptors mediating vasoconstriction are present on the garter snake aorta.
      However, in contrast to mammalian vessels, bothP2x and P2Y subtypes mediate
      vasoconstriction. There was no evidence for vasodilatation to ATP or analogues.
      Stimulation of the P2-purinoceptor by ATP and 2MeSATP caused the synthesis of a
      prostanoid. In addition, the possibility of a receptor activated by ATP, separate
      from P2X and P2Y subtypes is discussed since contractions to ATP proved to be
      insensitive to both PPADS and RB2. A comparison is made of purinoceptors in the
      garter snake aorta with those in other vertebrate vessels.

PMID- 7712028
TI  - Characterization of the interaction between muscarinic M2 receptors and beta
      adrenoceptor subtypes in guinea-pig isolated ileum.
AB  - 1. Contraction of guinea-pig ileum to muscarinic agonists is mediated by M3
      receptors, even though they account for only 30% of the total muscarinic receptor
      population. The aim of this study was to characterize the biochemical and
      functional effects of stimulation of the predominant M2 muscarinic receptor (70%)
      and to investigate the hypothesis that M2 receptors specifically oppose beta
      adrenoceptor-mediated effects in the ileum. 2. In guinea-pig ileal longitudinal
      smooth muscle slices, isoprenaline, a non-selective beta-adrenoceptor agonist,
      and BRL 37344 (sodium-4-[2-[2-hydroxy-2-(3- chlorophenyl)ethylamino]propyl]
      phenoxyacetate sesquihydrate), a beta 3-adrenoceptor selective agonist, increased
      cyclic AMP accumulation with -log EC50 values of 6.6 +/- 0.1 and 5.8 +/- 0.1
      respectively. Maximal stimulation by BRL 37344 (10 microM) was 26.4 +/- 5.2% of
      that observed with isoprenaline (10 microM). Isoprenaline (10 microM)-stimulated
      cyclic AMP accumulation was significantly, but not completely, inhibited by
      propranolol (5 microM), with a propranolol-resistant component of 28.2 +/- 6.8%
      of the maximal stimulation to isoprenaline. In contrast, basal and BRL 37344
      responses were resistant to this antagonist. These data provide evidence that
      both beta 1- and beta 3-adrenoceptors activate adenylyl cyclase in guinea-pig
      ileum. 3. Isoprenaline (10 microM)-stimulated cyclic AMP accumulation was
      inhibited (67.4 +/- 0.9%) by the muscarinic agonist (+)-cis-dioxolane (-log EC50
      = 7.3 +/- 0.1). The rank order of antagonist affinities against the (+)-cis
      dioxolane response was (-log KB values in parentheses): atropine (9.0 +/-
      0.2)>methoctramine (7.1 +/- 0.1) >p-fluoro-hexa-hydrosilaphenidol (p-F-HHSiD; 6.5
      +/- 0.2) ) pirenzepine(6.3 +/- 0.2). (+)-cis-dioxolane also significantly
      inhibited BRL 37344 (10 IM; 56.5 +/-2.4%) stimulated cyclic AMP accumulation.
      These data suggest that M2 receptors mediate inhibition of cyclic AMP
      accumulation in response to both beta l- and beta 3-adrenoceptor stimulation in
      guinea-pig ileum.4. 5-Hydroxytryptamine (5-HT), vasoactive intestinal peptide,
      prostaglandins E2 and E1, all at 10 micro M,significantly increased cyclic AMP
      accumulation. (+)-cis-Dioxolane (10 micro M) inhibited both basal and agonist
      induced cyclic AMP accumulation. Thus the inhibitory effect of M2 receptor
      agonism does not appear to be restricted to beta-adrenoceptor-stimulated cyclic
      AMP accumulation.5. The potential for involvement of activation of M2 receptors
      on responses to beta-adrenoceptor agonists was also studied functionally.
      Selective M3 receptor alkylation was achieved by pretreatment of tissues with 4
      DAMP mustard (40 nM), in the presence of methoctramine (1 micro M; to protect M2
      receptors). After washing, tissues were pre-contracted with histamine (0.3 micro
      M) and relaxed with isoprenaline (0.6 micro M).Under these conditions,
      oxotremorine M caused concentration-dependent contractions (-log EC50 of 7.8 +/-
      0.1), that were surmountably antagonized by methoctramine (1 microM) with a - log
      KB estimate of 7.4 +/- 0.1. Similar observations were seen versus relaxation
      produced by BRL 37344 (1 micro M), where the-log KB value for methoctramine was
      7.8 +/- 0.2. These data suggest that M2 receptors mediate a functional inhibition
      of relaxant responses to isoprenaline and BRL 37344.6. These findings are
      consistent with beta l- and beta 3-adrenoceptors coupling to stimulation of a
      denylylcyclase in guinea-pig ileum; a response that is inhibited by M2 receptor
      stimulation. Concordantly, M2 receptor stimulation also inhibits relaxation to
      both beta l- and beta 3-adrenoceptor stimulation. These results implicate M2
      receptors in the modulation of sympathetic control of ileal motility.

PMID- 7712029
TI  - Production of antinociception by peripheral administration of [Lys7]dermorphin, a
      naturally occurring peptide with high affinity for mu-opioid receptors.
AB  - 1. The opioid activity of the amphibian peptide, [Lys7]dermorphin, was studied in
      rats and mice. When administered intracerebroventricularly (i.c.v.),
      intravenously (i.v.) or subcutaneously (s.c.) it produced a long lasting
      analgesia. Its antinociceptive potency exceeded that of morphine 290 times by
      i.c.v. injection, and 25-30 times by peripheral administration. 2. The dose
      response curves of [Lys7]dermorphin antinociception were shifted to the right by
      the pretreatment with naloxone (0.1 mg kg-1, s.c.) or with the mu 1-selective
      antagonist, naloxonazine (10 mg kg-1, i.v. 24 h before peptide injection). 3. The
      peptide also displayed potent antinociceptive effects in a chronic inflammatory
      pain model (rat Freund's adjuvant arthritis). In this pain model, systemic
      administration of the peptide raised the nociceptive threshold more in inflamed
      than in healthy paw. 4. High central and peripheral doses of [Lys7]dermorphin in
      rats produced catalepsy. The cataleptic response was antagonized by naloxone but
      left unchanged by naloxonazine pretreatment. 5. In rats and mice, central or
      peripheral administration of [Lys7]dermorphin induced a significantly slower
      development of tolerance to the antinociceptive effect than did morphine. 6. Upon
      naloxone precipitation of the withdrawal syndrome, [Lys7]dermorphin-dependent
      mice made fewer jumps and lost less weight than the morphine-dependent animals.
      Withdrawal hyperalgesia did not develop in [Lys7]dermorphin-dependent mice. 7. In
      conclusion, [Lys7]dermorphin seems to be a unique opioid peptide having a high
      penetration into the blood-brain barrier despite its low lipid solubility. This
      peptide causes fewer side-effects than other opioids and appears less likely than
      morphine to cause physical dependence in rats and mice.

PMID- 7712030
TI  - Potentiation by aminopeptidase P of blood pressure response to bradykinin.
AB  - We examined whether a specific aminopeptidase P (APP) inhibitor, apstatin,
      increases vasodepressor responses to bradykinin in anaesthetized rats, and
      whether it would augment blood pressure responses further after treatment with
      the angiotensin-converting enzyme inhibitor (ACEi), lisinopril. Apstatin doubled
      the maximum blood pressure response to bradykinin. The area under the curve
      (AUC), which incorporates both peak blood pressure changes and duration of
      response, was doubled in apstatin-treated rats vs controls and in the
      apstatin+lisinopril group vs lisinopril alone. These data demonstrate that APP is
      an important kinase in vivo.

PMID- 7712031
TI  - Pharmacological characterization of bradykinin receptors in canine cultured
      tracheal smooth muscle cells.
AB  - 1. [3H]-bradykinin was used to characterize the bradykinin receptors associated
      with canine cultured tracheal smooth muscle cells (TSMCs). Receptor binding assay
      showed that TSMCs had specific, saturable, high-affinity binding sites for [3H]
      bradykinin. 2. The specific [3H]-bradykinin binding increased linearly with
      increasing cell concentrations. The equilibrium for association of [3H]
      bradykinin with the bradykinin receptors was attained within 2 h at 4 degrees C
      and 1 h at room temperature, respectively. 3. Analysis of binding isotherms
      yielded an apparent equilibrium dissociation constant (KD) of 2.5 +/- 0.3 nM and
      a maximum receptor density (Bmax) of 25.1 +/- 0.3 fmol mg-1 protein. The Hill
      coefficient for [3H]-bradykinin binding was 1.00 +/- 0.02. The association (K1)
      and dissociation (K-1) rate constants were (8.67 +/- 2.60) x 10(6) M-1 min-1 and
      0.024 +/- 0.005 min-1, respectively. KD, calculated from the ratio of K-1 and K1
      was 2.8 +/- 0.5 nM, a value close to that of KD calculated from Scatchard plots
      of binding isotherms. 4. The B1 receptor selective agonist, (des-Arg9-bradykinin,
      0.1 nM-10 microM) and antagonist ([Leu8, des-Arg9]-bradykinin, 0.1 nM-10 microM)
      did not did not inhibit the [3H]-bradykinin binding to TSMCs, which excludes the
      presence of B1 receptors in canine TSMCs. 5. The specific binding of [3H]
      bradykinin to canine TSMCs was inhibited by B2 receptor selective antagonists ([D
      Arg0, Hyp3, Thi5, D-Tic7, Oicl-bradykinin, Hoe 140, 0.1 nM-10 micro M and [D
      Arg0, Hyp3,Thi5,8, D-Phe7-bradykinin, 0.1 nM-10 micro M) and agonists (bradykinin
      and kallidin, 0.1 nM-10 micro M) with a best fit by a one-binding site model. The
      order of potency for the inhibition of [3H]-bradykinin binding was kallidin =
      bradykinin = Hoe 140> [D-Arg0, Hyp3, Thi5,8, D-Phel-bradykinin.6. Preincubation
      of TSMCs with forskolin for 24 h led to an up-regulation of B2 receptors,
      increasing in Bmax from 25.1 +/- 0.3 to 218 +/- 24 fmol mg-1 protein without
      changing the KD values. [3H]-bradykinin binding to TSMCs was inhibited by the B2
      receptor selective antagonists and agonists, but not by the B1 receptor selective
      reagents. The up-regulation of the B2 receptor by forskolin was mediated through
      protein synthesis, since cycloheximide blocked this response.7 It is concluded
      that the pharmacological characteristics of the bradykinin receptors in canine
      cultured TSMCs are primarily of the B2 receptor subtype.

PMID- 7712032
TI  - An enhancing effect of 5-hydroxytryptamine on electrically evoked atropine
      resistant contraction of guinea-pig proximal colon.
AB  - 1. In the presence of atropine (0.2 microM) and indomethacin (2 microM), the
      effects of 5-hydroxytryptamine (5-HT) have been studied on electrically-evoked,
      neurogenic contractions of the guinea-pig proximal colon in vitro. 2. 5-HT, at
      higher concentrations than 1 nM, caused an increase in electrically (1 Hz, 0.3
      ms, 160 mA)-evoked, atropine-resistant contractions in a concentration-dependent
      manner and at 30 nM produced a maximal effect (pEC50 value of 8.20 +/- 0.11, n =
      6). The enhancing effects of 5-HT on the electrically evoked contractions were
      mimicked by alpha-methyl-5-HT (pEC50 value of 6.59 +/- 0.05, n = 6). 3. Both
      hexamethonium (100 microM) and spantide (10 microM), selective antagonists for
      nicotinic and tachykinin receptors respectively, significantly reduced the
      enhancement of the electrically evoked contractions by 5-HT (30 nM). 4. DAU 6285
      (3 microM), a 5-HT4 receptor antagonist, abolished the enhancing action of 5-HT
      (30 nM), but metitepine (0.03 microM), a 5-HT1/5-HT2 receptor antagonist,
      ketanserin (0.01 microM), a 5-HT2 receptor antagonist, and ondansetron (1
      microM), a 5-HT3 receptor antagonist, had no effect on the enhancement. The
      enhancing effects of alpha-methyl-5-HT (1 microM) were also abolished by DAU 6285
      (3 microM). 5. Both 5-HT (30 nM) and alpha-methyl-5-HT (1 microM) had no effect
      on contractions to exogenous substance P (0.15-0.3 nM). 6. These results indicate
      that in the guinea-pig proximal colon, 5-HT produced an enhancement of atropine
      resistant neurogenic contraction induced by electrical field stimulation through
      pre-junctional mechanisms and that the enhancement is mediated by the stimulation
      of 5-HT4 receptors located on intramural preganglionic cholinergic neurones and
      tachykininergic neurones.

PMID- 7712033
TI  - Endotoxin inhibition of distension-stimulated gastric acid secretion in rat:
      mediation by NO in the central nervous system.
AB  - 1. The involvement of nitric oxide in the acute inhibitory effects of low doses
      of endotoxin, following intracerebroventricular (i.c.v.) or intravenous (i.v.)
      administration, on gastric acid secretion stimulated by distension or i.v.
      infusion of pentagastrin has been investigated in the continuously perfused
      stomach of the anaesthetized rat. 2. The i.c.v. administration of E. coli
      endotoxin (800 ng kg-1) abolished the acid secretory response induced by gastric
      distension (20 cm water intragastric pressure) within 30 min of administration.
      3. By contrast, submaximal rates of acid secretion induced by i.v. infusion of
      pentagastrin (8 micrograms kg-1 h-1) were not inhibited by i.c.v. administration
      of endotoxin (800 ng kg-1). 4. Prior i.c.v. administration of the NO synthase
      inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 800 micrograms kg-1)
      restored the acid secretory responses to distension in rats treated with
      endotoxin (i.c.v.). 5. Likewise, i.v. administration of endotoxin (5 micrograms
      kg-1) abolished the acid secretory response induced by gastric distension within
      30 min of administration. Prior i.c.v. injection of L-NAME (800 micrograms kg-1)
      or its i.v. administration (10 mg kg-1) restored acid secretory responses in rats
      receiving i.v. endotoxin. 6. The reversal by L-NAME (i.v.) of the acid inhibitory
      effects of endotoxin (i.v.) was prevented by L-arginine (12 mg kg-1, i.c.v. or
      100 mg kg-1, i.v.), but not by its enantiomer D-arginine. 7. The present results
      imply the existence of an acute response to endotoxin involving NO synthesis in
      the brain. NO may act as a neuromodulator or neurotransmitter in a nervous reflex
      leading to the inhibition of acid secretion stimulated by gastric distension.

PMID- 7712036
TI  - Clinical chemistry and coagulation.

PMID- 7712034
TI  - Interaction between gallopamil and cardiac ryanodine receptors.
AB  - 1. In a sarcoplasmic reticulum fraction obtained from rat hearts, the analysis of
      equilibrium [3H]-ryanodine binding showed high and low affinity sites (KD = 1.3
      nM and 2.8 microM, Bmax = 2.2 pmol mg-1 and 27.8 pmol mg-1). The dissociation
      rate constant increased at 1 microM vs 4 nM [3H]-ryanodine concentration, and
      micromolar ryanodine slowed the dissociation of nanomolar ryanodine. 2. The
      binding of 4 nM [3H]-ryanodine was not affected by gallopamil, while the binding
      of 100 nM to 18 microM [3H]-ryanodine was partly displaced. Data analysis
      suggested that gallopamil inhibited low affinity [3H]-ryanodine binding, with
      IC50 in the micromolar range. 3. Gallopamil decreased the dissociation rate
      constant of 1 microM [3H]-ryanodine. While gallopamil alone did not affect the
      dissociation of 4 nM [3H]-ryanodine, gallopamil and micromolar ryanodine slowed
      it to a greater extent than micromolar ryanodine alone. 4. Our results are
      consistent with the hypothesis that the ryanodine receptor is a negatively
      cooperative oligomer, which undergoes a sequential alteration after ryanodine
      binding. Gallopamil has complex actions: it inhibits ryanodine binding to its low
      affinity site(s), and probably modulates the cooperativity of ryanodine binding
      and/or the transition to a receptor state characterized by slow ryanodine
      dissociation. These molecular actions could account for the previously reported
      effect of gallopamil on the sarcoplasmic reticulum calcium release channel.

PMID- 7712035
TI  - Cytochrome P450-dependent effects of bradykinin in the rat heart.
AB  - 1. Vasodilator responses to bradykinin (BK) in the rat heart are reported to be
      independent of NO and cyclo-oxygenase/lipoxygenase products of arachidonic acid
      (AA). 2. We verified that inhibition of NO synthase with L-nitroarginine (50
      microM) and cyclo-oxygenase with indomethacin (2.8 microM) were without effect on
      vasodilator responses to BK (10-1000 ng) in the Langendorff rat heart
      preparation. 3. L-Nitroarginine elevated perfusion pressure, signifying a crucial
      role of NO in the maintenance of basal vasculature tone. 4. In hearts treated
      with L-nitroarginine to eliminate NO and elevate perfusion pressure, vasodilator
      responses were reduced by inhibitors of cytochrome P450 (P450), clotrimazole (1
      microM) and 7-ethoxyresorufin (1 microM). 17-Octadecynoic acid (17-ODYA 2
      microM), a mechanism based inhibitor of P450-dependent metabolism of fatty acids,
      also reduced vasodilator responses to BK. 5. These results confirm that NO and
      prostaglandins do not mediate vasodilator responses to BK in the rat heart but
      suggest a major role for a P450-dependent mechanism via AA metabolism.

PMID- 7712037
TI  - Nutrition and therapeutics.

PMID- 7712039
TI  - Lipid metabolism.

PMID- 7712038
TI  - Genetics and molecular biology.

PMID- 7712040
TI  - Cardiovascular disease and hyperlipidaemia.

PMID- 7712041
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 7712042
TI  - Clinical chemistry and coagulation.

PMID- 7712043
TI  - Clinical chemistry and coagulation.

PMID- 7712044
TI  - Characterization of low-density lipoprotein subclasses: methodologic approaches
      and clinical relevance.
AB  - Emerging evidence suggests that subclasses of LDL, characterized by variations in
      density, size, and chemical composition of LDL particles, are of important
      clinical significance. Accumulating case-control studies demonstrate that a
      predominance of small, dense LDL particles (LDL subclass phenotype B) is
      associated with an increased risk of coronary heart disease, and several
      potential atherogenic mechanisms have been proposed. New studies also demonstrate
      that LDL subclass phenotype B is an integral feature of the insulin resistance
      syndrome. In addition to the well-documented genetic influences on LDL subclass
      distributions, lipid-altering drugs, diet, and exercise all appear to affect LDL
      subclasses. A better understanding of this combination of genetic and
      environmental influences could lead to the development of effective intervention
      strategies for the prevention of coronary heart disease.

PMID- 7712045
TI  - Physiological role and clinical relevance of high-density lipoprotein subclasses.
AB  - Low HDL cholesterol is an important predictor of cardiovascular risk.
      Considerable effort has been undertaken to improve the predictive value of HDL
      cholesterol by the quantification of HDL subclasses. Controversy still exists as
      to whether quantification of apolipoprotein A-I, selective precipitation of HDL2,
      or differential immunoassays of apolipoprotein A-I-containing particles improve
      the diagnostic value of HDL cholesterol. Some quantitatively minor subclasses of
      HDL, namely pre-beta-1-lipoprotein(AI) and gamma-lipoproteinE, contribute
      significantly to the release of cellular cholesterol into the plasma compartment,
      and possibly to the antiatherogenic role of HDL. These particles can only be
      separated from the bulk of HDL by laborious electrophoretic techniques that,
      although provide important insights into the physiology of reverse cholesterol
      transport, are not suitable for clinical laboratories. Thus, to date, clinicians
      are not recommended to extend the measurement of HDL cholesterol to include the
      determination of HDL subclasses.

PMID- 7712046
TI  - Lipoprotein(a) quantification: comparison of methods and strategies for
      standardization.
AB  - Despite an exponential increase in the number of published papers reporting the
      clinical significance of lipoprotein(a), it is very difficult to relate the
      lipoprotein(a) data obtained from different studies because of wide
      dissimilarities in the reported values. Methodological aspects such as
      differences in assay design, degree of optimization, antibody source,
      calibration, and the expression of lipoprotein(a) values are the main
      contributors to the observed lack of comparability. A major effort in the
      evaluation and standardization of lipoprotein(a) assays is required to fully
      evaluate the clinical potential of lipoprotein(a) measurements.

PMID- 7712047
TI  - Lipoprotein oxidation: mechanistic aspects, methodological approaches and
      clinical relevance.
AB  - The oxidation of LDL is now commonly implicated as an initiator of
      atherosclerosis and a standard in-vitro LDL 'oxidizability' test is required.
      This review will discuss current problems and advances that have been made in our
      understanding of the molecular mechanisms of radical-mediated LDL oxidation and
      antioxidation, how they relate to the in-vitro assessment of the 'oxidizability'
      of LDL and how they may be relevant to in-vivo LDL oxidation. Tocopherol-mediated
      peroxidation is used as a novel model of LDL lipid oxidation to discuss why terms
      such as 'lag time' are features of the in-vitro oxidation conditions, rather than
      being inherent to LDL oxidation per se. In addition, we will also cover why it is
      premature, at present, to use one particular LDL oxidizability test as a
      standard.

PMID- 7712049
TI  - The relationship between white blood cells and arterial disease.
AB  - The white blood cell is conventionally associated with the processes of
      inflammation and immunity. Epidemiological and behavioural studies are now
      showing a link between the white blood cell and vascular disease. This cell can
      contribute both to atherogenesis and to thrombosis, and is important in
      contributing to reperfusion injury through the generation of free radicals.
      Recent evidence in support of the white blood cell as a new risk factor for
      vascular disease is evaluated in this review.

PMID- 7712048
TI  - Tissue factor pathway inhibitor: a potent inhibitor of in-vitro coagulation and
      in-vivo thrombus formation.
AB  - Tissue factor pathway inhibitor is established as an important coagulation
      inhibitor. The knowledge of the relationship between the structure and function
      of the tissue factor pathway inhibitor molecule has been widely expanded,
      especially with regard to its interaction with heparin. Perhaps the most
      important and promising new studies have investigated the possibility, of using
      tissue factor pathway inhibitor as a potent drug in the treatment of experimental
      septic shock and arterial and venous thrombosis.

PMID- 7712050
TI  - A twin study of the association of post-traumatic stress disorder and combat
      exposure with long-term socioeconomic status in Vietnam veterans.
AB  - This study examines the association between post-traumatic stress disorder (PTSD)
      and combat exposure with the socioeconomic status of 2210 male monozygotic
      veteran twin pairs in 1987. In the unadjusted analysis on individuals, modest
      correlations indicated that those with PTSD were more likely to have been
      divorced, and less likely to be currently employed or to achieve high status in
      income, education or occupation. In the crude analysis of veterans not suffering
      from PTSD, there were small positive correlations between combat level
      experienced and the likelihood of ever being married, ever being divorced, and
      the number of years employed at the current job. However, when we examined
      identical twins discordant for PTSD, and adjusted for pre-military and military
      service factors, only unemployment remained significant. Likewise, in combat
      discordant twins, no significant effects on the socioeconomic indicators were
      seen. We conclude that PTSD and combat experience in Southeast Asia have not had
      a major impact on the socioeconomic status of veterans.

PMID- 7712051
TI  - Warzone violence in Vietnam: an examination of premilitary, military, and
      postmilitary factors in PTSD in-patients.
AB  - The impact of childhood victimization and other premilitary factors on warzone
      abusive violence was examined with 177 Vietnam combat veteran inpatients.
      Premilitary and military variables were also examined in relationship to
      postmilitary variables, including violence and PTSD. Statistical analyses showed
      that none of the premilitary variables predicted warzone violence. High combat
      exposure did, however, predict warzone abusive violence and PTSD. In addition,
      participation in warzone violence predicted postmilitary violence to self,
      spouse, and others. Although high rates of childhood victimization and high
      levels of combat exposure were found, neither predicted postmilitary violence,
      criminal activities, drug/alcohol problems, or suicide attempts. Low childhood
      adjustment ratings and school suspensions predicted adult alcohol abuse and drug
      abuse, respectively. These findings and their implication for treatment are
      discussed.

PMID- 7712052
TI  - Lithium for irritability in post-traumatic stress disorder.
AB  - Irritability is often a problem for patients with Post-Traumatic Stress Disorder
      (PTSD). We describe two cases that illustrate the use of lithium in the treatment
      of veterans with PTSD who complained of serious problems with irritability or
      angry outbursts. These cases are discussed in the context of evidence that
      lithium may be useful in other patients with disorders of impulse control. The
      evidence linking disorders of anger and impulse control to a dysregulation in
      neurotransmitter regulation, particularly in serotonergic pathways, supports a
      psychopharmacologic approach to treatment. These findings should lead to further
      study of the role of lithium in the treatment of this symptom complex in patients
      with PTSD.

PMID- 7712053
TI  - Myocardial infarction and post-traumatic stress disorder.
AB  - Studies concerning the development of a post-traumatic stress disorder related to
      severe illness are scarce. The confrontation with myocardial infarction may be a
      very stressful event. Twenty-three patients consecutively admitted for first
      myocardial infarction were studied. After two years 1 of 18 survivors had been
      suffering from a partial post-traumatic stress disorder. Similarities and
      differences in the psychological reactions following potential traumatic events
      are discussed.

PMID- 7712054
TI  - Confidants' feedback and traumatic life events.
AB  - One hundred six undergraduate (83 women and 23 men) completed surveys concerning
      their most traumatic life event, the feedback they received following their
      disclosure of the event to others, and how they felt after the disclosure.
      Results indicated that the better they felt after disclosure, the less disturbed
      they were by thoughts of the event at the time of the study. In addition, the
      more personal the trauma was, the worse they felt after their disclosure, and the
      more disturbed they were about the trauma. However, no significant relation
      existed between the positivity (e.g., supportiveness) of their confidant's
      feedback and their present degree of disturbance. Implications for understanding
      the complex relation between confiding traumatic events and resolving feelings
      surrounding those events were discussed.

PMID- 7712055
TI  - Post-traumatic stress disorder and the MMPI-2.
AB  - This study compared the MMPI-2 profiles of 27 veterans diagnosed with post
      traumatic stress disorder with a non-PTSD comparison group of 27 veteran patients
      receiving inpatient treatment for other mental disorders. Three multivariate
      analyses of variance were conducted comparing the two groups on the 10
      traditional clinical scales, the 12 supplemental scales and the 15 new content
      scales on the MMPI-2. The PTSD group obtained a mean profile with peak elevations
      on the F validity scale and on clinical Scales 2 (D) and 8 (Sc). The multivariate
      analysis of variance comparing the PTSD and non-PTSD groups across the 10
      traditional clinical scales was not significant. The multivariate analyses of
      variance comparing the two groups on the 12 supplemental scales and the 15
      content scales were significant. Significant univariate supplemental scale
      differences were found on the Keane PTSD scale (PK) and the Post-Traumatic Stress
      Disorder (PS) scale with the PTSD group scoring higher on PK and PS. Significant
      univariate content scale differences were found for the Anger (ANG) scale with
      the PTSD group scoring higher. A cut-off score of 28 on the PK scale correctly
      classified 76% of the overall sample, 67% of the PTSD group and 85% of the non
      PTSD-comparison group.

PMID- 7712056
TI  - Adult trauma survivors and post-traumatic stress sequelae: an analysis of
      reexperiencing, avoidance, and arousal criteria.
AB  - The relationship of traumatic events to DSM-III criteria symptoms for post
      traumatic stress disorder was examined in a randomized community survey (N =
      2,364) of Los Angeles residents. Multivariate analysis of covariance revealed
      that both demographic factors and the type of traumatic event influenced
      respondents' reports of reexperiencing, avoidance, and arousal symptoms after the
      event.

PMID- 7712057
TI  - When disaster strikes, acute stress disorder may follow.
AB  - During and immediately following a traumatic event, people may manifest a pattern
      of dissociative and anxiety symptoms and other reactions, referred to as Acute
      Stress Disorder. A review of the empirical literature on psychological reactions
      to trauma suggest that this pattern of symptoms has often been identified across
      different kinds of traumatic events. It is likely to constitute a psychological
      adaptation to a stressful event, limiting painful thoughts and feelings
      associated with the event and allowing the person to function at least minimally.
      Continuation of these symptoms, however, may impair the person's quality of life
      and disrupt social and other functioning. If symptoms last beyond a month
      following the traumatic event, Post Traumatic Stress Disorder (PTSD) may ensue,
      continuing for months or even years after the precipitating event. Hence, it is
      important to be able to identify this pattern of reactions that may be manifested
      in reaction to trauma, so that appropriate intervention can be provided. Although
      it was not officially recognized in the 3rd edition Diagnostic and Statistical
      Manual (DSM-III-R), Acute Stress Disorder is included as a separate diagnosis in
      the DSM-IV.

PMID- 7712058
TI  - Psychological adaptation among residents following restart of Three Mile Island.
AB  - Psychological adaptation is examined in a sample of residents who remained in the
      vicinity of Three Mile Island following the restart of the nuclear generating
      facility which had been shut down since the 1979 accident. Findings indicate a
      lowering of psychological symptoms between 1985 and 1989 in spite of increased
      lack of control, less faith in experts and increased fear of developing cancer.
      The suggestion is made that reduced stress might have been related to a process
      of adaptation whereby a cognition of emergency preparedness was integrated by
      some of these residents as a modulating cognitive element. Findings also indicate
      that "loss of faith in experts" is a persistently salient cognition consistent
      with the "shattered assumptions" theory of victimization.

PMID- 7712059
TI  - Hearing people through their pain.
AB  - The first goal in this clinical and theoretical essay is to specify what it means
      to hear people through their pain, by articulating intuitions that are seldom put
      in formal terms. "What" and "how" and "whom" we hear shift depending on whether
      we are (1) uncovering the facts, (2) appreciating their meaning with another's
      life, (3) drawing out and enlivening the one who has to live with and make sense
      of traumatic experience, or (4) engendering, by having others hear that they are
      heard, enough relatedness to establish a meaningful precedent for their lives. A
      second goal here is to show how the meaning of trauma changes as hearing deepens.
      Accordingly, we may hear in people's trauma (1) psychophysical reactions to
      events; (2) the playing out of themes from a lifetime; (3) violations whose inner
      message is a demand to awaken beyond self-protective ways of being; and (4) a
      uniquely powerful opening for communion.

PMID- 7712060
TI  - Differential effects of trauma on spouses of traumatized households.
AB  - The responses of 60 households subjected to varying degrees of traumatic events
      were examined. Specific attention was given to the differential effect that
      traumatic events have on spouses, especially in terms of general anxiety, state
      anxiety, trait anxiety, depression, and other symptoms related to trauma. The
      findings showed that degree of traumatization was proportional to number and
      intensity of stress related symptoms. Mothers, however, manifested depression and
      anxiety levels twice as high as fathers. The validity of these results was
      discussed in terms of cultural beliefs and practices.

PMID- 7712061
TI  - The development of a Clinician-Administered PTSD Scale.
AB  - Several interviews are available for assessing PTSD. These interviews vary in
      merit when compared on stringent psychometric and utility standards. Of all the
      interviews, the Clinician-Administered PTSD Scale (CAPS-1) appears to satisfy
      these standards most uniformly. The CAPS-1 is a structured interview for
      assessing core and associated symptoms of PTSD. It assesses the frequency and
      intensity of each symptom using standard prompt questions and explicit,
      behaviorally-anchored rating scales. The CAPS-1 yields both continuous and
      dichotomous scores for current and lifetime PTSD symptoms. Intended for use by
      experienced clinicians, it also can be administered by appropriately trained
      paraprofessionals. Data from a large scale psychometric study of the CAPS-1 have
      provided impressive evidence of its reliability and validity as a PTSD interview.

PMID- 7712062
TI  - The civilian version of the Mississippi PTSD Scale: a psychometric evaluation.
AB  - This three-part study examined the reliability and validity of the civilian
      version of the Mississippi Scale for Combat-Related PTSD using data from the
      nonveteran participants in the National Vietnam Veterans Readjustment Study. The
      Civilian Mississippi Scale had a raw score distribution that was roughly
      symmetric, with an acceptable degree of dispersion and a reasonably high internal
      consistency reliability coefficient. Overall, however, measurement precision was
      weaker than that for the military version of the instrument, and confirmatory
      factor analytic findings differed from those found for the military version.
      Preliminary investigations of validity were in the form of correlations with
      indices of stressful life events, a PTSD symptom count, and measures of
      demoralization and active expression of hostility. The Civilian Mississippi Scale
      emerged from the various analyses as a PTSD measure with potential but requiring
      further validational study and perhaps some refinement.

PMID- 7712064
TI  - Localization of octopaminergic neurones in insects.
AB  - This paper reviews data on the localization of octopaminergic neurons revealed by
      immunocytochemistry in insects, primarily the locusts Schistocerca gregaria and
      Locusta migratoria, cricket Gryllus bimaculatus, and cockroach Periplaneta
      americana. Supporting evidence for their octopaminergic nature is mentioned where
      available. In orthopteran ventral ganglia, the major classes of octopamine-like
      immunoreactive (-LI) neurones include: (1) efferent dorsal and ventral unpaired
      median (DUM, VUM) neurones; (2) several intersegmentally projecting DUM
      interneurones in the suboesophageal ganglion; other DUM interneurones are
      probably GABAergic; (3) a pair of anterior median cells in the prothoracic
      ganglion; (4) a single pair of ventral cells in most thoracic and some other
      ganglia; these appear to be plurisegmentally projecting interneurones. Eight
      categories of octopamine-LI neurones occur in the orthopteran brain. The basic
      projections of three types are described here: one class project to the optic
      lobes to form wide field projections. Another type descends to cross into the
      tritocerebral commissure and may invade the contralateral brain hemisphere. A
      further class is the median neurosecretory cells with axons in the nervi corpori
      cardiaci I. Available data for the honey bee Apis mellifera and moth Manduca
      sexta indicate that the octopamine-LI cell types found in orthopterans also occur
      in holometabolous insects. Immunocytochemical evidence suggests that some
      octopaminergic DUM cells contain an FMRFamide-related peptide and the amino acid
      taurine as putative cotransmitters.

PMID- 7712063
TI  - Optomotor-blind of Drosophila melanogaster: a neurogenetic approach to optic lobe
      development and optomotor behaviour.
AB  - The gene optomotor-blind (omb) plays a crucial role in Drosophila optic lobe
      development. Various mutations in omb lead to different structural defects in the
      adult optic lobes with correlated behavioural phenotypes. Molecular analysis of
      omb allows one to trace back behavioural defects to the spatio-temporal
      misexpression of the gene in mutant development.

PMID- 7712065
TI  - Electroreceptors: involvement of excitatory amino acids in synaptic transmission.
AB  - Electroreceptors are present in the skin of fish, amphibia and lower mammals,
      e.g. platypus. Animals use these receptors for detecting weak electric and
      magnetic fields. Electroreceptors of fish and amphibia belong to the secondary
      receptors in which the primary transduction is carried out by neuroepithelial
      hair cells that transmit synaptically to the afferent nerve fibers. The role of
      excitatory amino acids in synaptic transmission in electroreceptors is the
      subject of this review.

PMID- 7712066
TI  - Captopril normalises systolic blood pressure in rats with hypertension induced by
      fetal exposure to maternal low protein diets.
AB  - Recent studies have demonstrated that the feeding of low protein diets to rats
      during pregnancy induces hypertension in their offspring. Maternal-diet-induced
      hypertension has been previously associated with elevated pulmonary angiotensin
      converting enzyme (ACE) activity. In the present study, the importance of the
      renin angiotensin system, and in particular ACE, in the maintenance of the
      hypertensive state, is investigated. Pulmonary and plasma ACE activity were
      determined in rats of different ages, following in utero exposure to 18 (control)
      or 9% (deficient) casein diets. No maternal diet induced changes in pulmonary ACE
      were noted, but at 4 and 13 weeks of age, plasma ACE activity was increased by 34
      and 134%, respectively in 9% casein exposed rats relative to controls (P <
      0.001). Thirteen-week-old rats had significantly raised systolic blood pressure
      (28 mmHg, P < 0.05), and tended to have higher diastolic blood pressure (not
      significant). These hypertensive animals had slightly raised plasma angiotensin
      II concentrations (30% higher, not significant), but similar renin activities,
      when compared with normotensive controls. Treatment of normotensive and
      hypertensive rats with the ACE inhibitor captopril demonstrated that higher
      plasma ACE activity may play a major role in the maintenance of maternal-diet
      induced hypertension. Whilst normotensive rats showed no significant response to
      drug treatment, systolic blood pressure in the hypertensive rats fell rapidly to
      the level observed in the normotensive control group. Blood pressure remained at
      this lower level until treatment was withdrawn, at which time pressure began to
      increase slowly, but steadily. A period of 7-8 weeks was required following
      cessation of captopril administration for the restoration of
      hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712067
TI  - Mineral absorption and secretion patterns in the alimentary tract of the roe deer
      (Capreolus capreolus).
AB  - Concentrations of macrominerals; Na, K, Ca, Mg, P, and Cl were measured in
      different sections of the alimentary tract of five roe deer, Capreolus capreolus,
      kept in captivity and fed a diet of grass pellets and oats. By means of the non
      absorbed marker-slaughter technique (using 51CrEDTA as marker), sites of
      secretion and absorption of minerals in the alimentary tract were determined.
      Large amounts of P, Na and K were secreted into the rumen, whereas Cl was
      secreted into the abomasum. The larger amounts of these minerals were absorbed
      from the distal small intestine and caecum/proximal colon. In the coiled colon,
      small quantities of Na, K and Cl were absorbed which is essential for the
      maintenance of mineral balance. Emphasis is put on the role of the large hindgut
      in concentrate selectors both with respect to fermentation and conservation of
      minerals and other nutrients.

PMID- 7712068
TI  - Copper metabolism in analbuminaemic rats fed a high-copper diet.
AB  - Copper metabolism in male Nagase analbuminaemic (NA) rats was compared with that
      in male Sprague Dawley (SD) rats fed purified diets containing either 5 or 100 mg
      Cu/kg diet. Dietary copper loading increased hepatic and kidney copper
      concentrations in both strains to the same extent, but baseline values were
      higher in the NA rats. There was no strain difference in true and apparent copper
      absorption nor in faecal endogenous and urinary copper excretion. NA rats had
      higher levels of radioactivity in kidneys at 2 hr after intraperitoneal
      administration of 64Cu. As based on the distribution of added 64Cu, about 70% of
      plasma copper appeared to be in the non-protein compartment in the NA rats,
      whereas in SD rats, it was only about 1%. It is concluded that the NA rats are
      able to maintain a relatively normal metabolism of copper, even after dietary
      copper challenge. In the NA rats, zinc concentrations in kidneys, liver and
      urinary zinc excretion were elevated when compared with SD rats. The high-copper
      diet did not affect tissue zinc concentrations and apparent zinc absorption in
      both strains of rats.

PMID- 7712069
TI  - Beyond sex differences in visuo-spatial processing: the impact of gender trait
      possession.
AB  - Much research has emphasized the presence of sex differences in visuo-spatial
      processes while neglecting individual differences in performance within the two
      sexes (Archer, 1987). The present study looks beyond sex differences and
      considers the association of self-perceived gender trait possession with
      performance in two visuo-spatial tasks. The findings indicate that, in a 3-D
      mental rotation task, where a substantial sex difference occurred, gender trait
      possession adds significantly to the overall explanation of performance, the
      important gender trait variable being a measure of androgyny. With the Group
      Embedded Figures Task, gender trait measures were the only significant variables
      in differentiating performance, in this case masculinity was the important gender
      trait variable. The implication of such results for conventional explanations of
      individual differences in visuo-spatial processing is discussed.

PMID- 7712070
TI  - Development of face recognition.
AB  - In this article, research findings from studies which have examined the
      developmental pattern for recognition of unfamiliar faces and relevant theories
      are reviewed. Recognition of faces was found to improve with age from about five
      years to adulthood, with some studies reporting a dip during early adolescence.
      Two neuropsychological explanations (development of hemisphere specialization and
      maturational changes) and four information processing explanations (depth of face
      processing, pattern of feature salience, development of face schema, and encoding
      shift) are described and assessed for their tenability in light of reported
      findings. Explanations for the developmental dip are also discussed. Since these
      explanations failed to receive sufficient empirical support, an alternative
      explanation in terms of increasing efficiency of encoding is proposed.

PMID- 7712071
TI  - The sense of community.

PMID- 7712072
TI  - How to think change.

PMID- 7712073
TI  - Get with the programme.

PMID- 7712074
TI  - Nursing management? Does not compute...

PMID- 7712075
TI  - Power to the people (with care).

PMID- 7712076
TI  - Nurse education goes better with formula NVQ.

PMID- 7712077
TI  - Research for a happy ending.

PMID- 7712078
TI  - Nurses bear the brunt of insecurity.

PMID- 7712079
TI  - The nurses' pay Review Body recommendations for this year.

PMID- 7712080
TI  - Still second best.

PMID- 7712081
TI  - Clinical supervision--take it from the top.

PMID- 7712082
TI  - [Flavonoids in the prevention of cancer].
AB  - The paper summarizes the possibilities of using flavonoids in the treatment and
      especially prevention of human cancer. It also describes the probable mechanism
      of protective actions of food flavonoids.

PMID- 7712083
TI  - [Chromopharmacokinetics and chromopharmacodynamics of drugs].
AB  - The review includes results of studies on the influence of biological rhythms in
      pharmacokinetics and pharmacodynamics of drugs. Rhythmical changes in
      physiological functions of the organism can change pharmacokinetic parametres.
      Their values depend on the time of administration. The properties and the number
      of receptors in the target tissue can also be under influence of time and in this
      way pharmacodynamic effect can be influenced. The results of
      chronopharmacological studies can be used in clinical practice and pharmaceutical
      research.

PMID- 7712084
TI  - Skin grafts.

PMID- 7712085
TI  - Stump the experts.

PMID- 7712086
TI  - Local therapy for mucocutaneous Kaposi's sarcoma in patients with acquired
      immunodeficiency syndrome.
AB  - BACKGROUND: Kaposi's sarcoma (KS) accounts for significant morbidity in AIDS
      patients. Lessons are often numerous, disfiguring, painful, and may interfere
      with function. Although generalized therapy is available, local treatment is
      often more desirable. OBJECTIVE: To summarize the available data on local therapy
      for KS. METHODS: Literature was searched using Medline. RESULTS: Excision, laser
      destruction, cryotherapy, intralesional chemotherapy, immunotherapy, and
      radiation therapy were compared for success rate, cost, and convenience.
      CONCLUSION: Intralesional therapy, cryotherapy, and radiation all have
      substantial advantages over excision or laser surgery. Choice of the appropriate
      modality varies with different sites and patients.

PMID- 7712087
TI  - Photoelastic models of wound closure stress.
AB  - BACKGROUND: Areas of high stress in surgical closures are known to have adverse
      effects on wound healing. OBJECTIVE: To create a surgical model that will predict
      areas of high stress and allow for quantitative comparison of stress
      distributions in different closure geometries. METHODS: Surgical models were
      constructed consisting of soft polyurethane plastic. Surgical defects
      corresponding to A to T and O to T closures were cut in the plastic and then
      closed with silk interrupted sutures. The models were transilluminated with
      polarized light, photographed, and compared. RESULTS: The A to T closure showed
      much less total stress than the O to T closure. The color-coded stress patterns
      indicate that each closure has its own distinct stress characteristics.
      CONCLUSION: Photoelastic surgical models allow rapid and easy comparison of
      stress concentrations in different closure geometries. Such detailed information
      may allow the surgeon to avoid the adverse consequences of stress.

PMID- 7712089
TI  - Perichondrial cutaneous grafts for reconstruction of skin cancer excision
      defects.
AB  - BACKGROUND: Perichondrial cutaneous grafts (PCCGs) are composite grafts comprised
      of skin and subjacent perichondrium. Animal models and preliminary clinical
      reports have shown that PCCGs are thicker, survive better and contract less than
      full-thickness skin grafts, and are simpler to perform that alternative
      reconstructive methods such as two-stage flaps. OBJECTIVE: The applicability of
      PCCGs to surgical defects following Mohs surgery was investigated. METHODS: PCCGs
      were used to reconstruct patients with surgical defects following Mohs excision
      of skin cancers from facial sites near free anatomic margins and in defects with
      exposed cartilage. RESULTS: A series of cases is described, all with good to
      excellent cosmesis and function. CONCLUSION: PCCGs are useful in reconstruction
      of defects following Mohs excision of skin cancers.

PMID- 7712090
TI  - The efficacy of a topical lidocaine/prilocaine anesthetic gel in 35%
      trichloroacetic acid peels.
AB  - BACKGROUND: A topical formulation of lidocaine and prilocaine has been shown to
      provide effective anesthesia for certain superficial skin treatments. OBJECTIVE:
      To evaluate the efficacy of a topical self-occluding gel containing lidocaine
      2.5% and prilocaine 3.5% in reducing the discomfort of 35% trichloroacetic acid
      (TCA) peels. METHODS: Ten patients who had previously undergone 35% TCA peels
      were treated with this anesthetic gel prior to their second 35% TCA peel. They
      rated their level of discomfort in comparison with their previous peel with no
      anesthesia. RESULTS: Eight of 10 patients reported at least a 40% reduction in
      discomfort. However, there was a tendency for the anesthetic gel to enhance the
      depth of the peel. CONCLUSION: Topical lidocaine/prilocaine gel is an effective
      agent for reducing the discomfort associated with 25% TCA peeling. However, it
      should only be used with TCA below 30% concentrations due to its ability to
      enhance the depth of the peel.

PMID- 7712088
TI  - The treatment of palmar and plantar warts using natural alpha interferon and a
      needleless injector.
AB  - BACKGROUND: The treatment of palmar and plantar warts is difficult and often
      frustrating. The need for multiple destructive treatments and recurrences after
      apparent cure are common. OBJECTIVE: The purpose of this study was to determine
      if intralesional natural alpha interferon might offer an effective alternative
      therapy for common plantar and palmar warts. METHODS: A series of 22 private
      office patients with palmar and plantar warts were treated with intralesional
      natural alpha interferon using a needless injector. We treated twice weekly for a
      minimum of 8 weeks or until clear. RESULTS: Sixteen patients (73%) showed
      complete clearing of their warts in a mean of 11 weeks of twice weekly treatment.
      Upon follow-up, which averaged 9.5 months, 17 of 21 patients (81%) remained clear
      of their warts. CONCLUSION: Natural alpha interferon by needless injector appears
      to represent an effective alternative treatment for palmar and plantar human
      papillomavirus lesions. Further study of this modality is indicated.

PMID- 7712091
TI  - Is dermatologic usage of coal tar carcinogenic? A review of the literature.
AB  - BACKGROUND: Coal tar ointments have been used for decades in the treatment of
      various dermatoses, most notably eczema and psoriasis. Occupational exposure to
      coal tar poses an increased risk of developing cutaneous malignancies. The
      evidence of an increased risk of skin cancer in humans, as a result of
      dermatologic usage of tar, however, is conflicting. OBJECTIVE: A consensus on the
      carcinogenicity of tar is sought. METHODS: The existing literature (in vitro,
      animal, and human studies) on this subject is reviewed. RESULTS: The
      carcinogenicity of coal tar has clearly been demonstrated by in vitro and animal
      studies, and appears to be potentiated by concomitant use of ultraviolet
      radiation. Systemic absorption of mutagens from topically applied tar has been
      demonstrated in humans. Epidemiologic studies in humans, however, have not
      definitively shown an increase in skin cancer with therapeutic use of tar.
      CONCLUSIONS: Conclusive evidence for the carcinogenicity of tar used in
      dermatologic practice is lacking. Further controlled studies are necessary.

PMID- 7712092
TI  - A scalp garment for prestretching prior to alopecia-reducing procedures.
AB  - BACKGROUND: This article demonstrates a scalp stretching device that improves
      scalp laxity prior to alopecia reducing procedures. This device replaces the
      former use of vigorous, preoperative scalp stretching exercises. OBJECTIVE: To
      improve scalp laxity prior to alopecia-reducing procedures by using a device
      rather than vigorous prestretching exercises, which are physically fatiguing.
      METHOD: A scalp stretching device was developed that uses the principle of cyclic
      loading in the immediate preoperative period and the principle of biologic creep
      during the month prior to the procedure. This device is simply applied by
      patients at home for 30 minutes per day starting 30 days before an alopecia
      reducing procedure. RESULTS: The device demonstrates ease of use for the patients
      and does not require any physical activity on their part. It accomplishes the
      same improvement in laxity that prestretching exercises formerly achieved.
      CONCLUSION: The scalp stretching garment introduced improves the laxity of the
      scalp prior to alopecia-reducing procedures with no physical exertion being
      required by the patient.

PMID- 7712093
TI  - Noninvasive undermining. An innovative adjunct to scalp surgery [ comment].

PMID- 7712094
TI  - The Q-switched Alexandrite laser's effects on tattoos in guinea pigs and
      harvested human skin.
AB  - BACKGROUND: Developmental work in tattoo removal is currently carried out in
      animal models whose skin has different optical and mechanical properties from
      human skin. OBJECTIVE: To observe laser effects on tattoos in a new human skin
      model and that of in vivo guinea pig skin. METHODS: A comparison of the efficacy
      of the Q-switched Alexandrite laser (750 nm, 100-120 nanoseconds) in tattooed
      harvested human skin and guinea pig skin was performed. Visual assessments as
      well as histologic and electron microscopy evaluation before and after treatment
      are reported. RESULTS: Mild to moderate clearing of black tattoo pigment, as
      judged by visual assessment, was found after one laser treatment in both the in
      vitro human skin model and guinea pig skin. Blue and green ink showed similar
      results to black ink in human skin whereas red and yellow ink did not respond in
      our model. CONCLUSION: Possible mechanisms of tattoo lightening and the
      usefulness of the in vitro human skin model are discussed.

PMID- 7712095
TI  - Xylene substitutes in frozen sections.
AB  - BACKGROUND: Toxic exposure to xylene may occur during routine histopathologic
      staining procedures. Safer xylene substitutes have been available for over a
      decade, however, a 1991 survey of 25 Mohs training programs revealed that only
      56% were using xylene substitutes. OBJECTIVE: The purpose of this study was to
      compared xylene to xylene substitutes in the histologic preparation of frozen
      sections with respect to staining quality, clarity, cellular detail, and tissue
      distortion. METHODS: Xylene and xylene substitutes were used as the final
      clearing agent in the routine histologic preparation of fresh frozen horizontal
      sections. The slides were evaluated by a dermatopathologist and a Mohs surgeon in
      a blinded manner. RESULTS: No difference between xylene and the xylene
      substitutes were noted. CONCLUSION: In light of the improved safety profile and
      efficacy of the xylene substitutes, they should replace xylene in the Mohs
      laboratory.

PMID- 7712096
TI  - Dermabrasion of the hyperkeratotic foot.
AB  - BACKGROUND: Keratoderma is a common problem. Its treatment is difficult and may
      be associated with systemic side effects. OBJECTIVE AND METHOD: To describe the
      use of dermabrasion for hyperkeratotic conditions of the palms and soles.
      RESULTS: Dermabrasion of keratoderma is an easy, quick, and safe method that
      brings immediate relief to patients, allows improved penetration of topical
      medications, and facilitates the control of the underlying disease with simple
      measures. CONCLUSIONS: Dermabrasion should be considered among the treatment
      options for keratoderma.

PMID- 7712097
TI  - Pilomatrixoma of the earlobe.
AB  - BACKGROUND: Pilomatrixoma most commonly occurs in the head and neck region,
      appearing primarily in the first two decades of life. The lesion is described as
      a tumor with differentiation toward hair cells and surgical excision is the
      treatment of choice. OBJECTIVE: We report an uncommon localization of a
      perforating type pilomatrixoma of 5 x 4 x 4 cm in size that developed from the
      earlobe. METHODS: Histopathological examination revealed pilomatrixoma. Total
      resection of the tumor was performed. The earlobe was reconstructed by forming a
      posterior-superior pedicled skin flap. RESULTS: No recurrence was observed and a
      good cosmetic result was obtained. CONCLUSION: Local recurrence does not
      generally occur if the tumor is completely removed. The case we present is of
      interest in having a history of trauma to the region and a relatively rapid
      growth with perforation of the overlying skin.

PMID- 7712098
TI  - Basal cell carcinoma on the scalp of an Indian patient.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in whites,
      but it rarely occurs in dark persons. OBJECTIVE: To report a BCC on the hairy
      scalp of an Asian Indian female with no obvious risk factors except previous
      scalp trauma. METHODS: We review the English literature concerning BCC in
      Indians, and compare this with data for North American blacks and whites; and
      reports of BCC arising in areas of prior trauma. RESULTS/CONCLUSION: Skin cancer
      accounts for 1-2% of malignancies in blacks and Indians, compared with one-third
      of neoplasms in whites. BCC comprises 75% of skin cancers in whites, but squamous
      cell carcinoma represents 60-65% of skin cancers in blacks and Indians. Although
      most BCCs occur in sun-exposed areas in whites, blacks, and Indians, a
      significant percentage also develop in photoprotected areas. Trauma may be a
      significant risk factor for BCC, either with actinic damage or alone, as in our
      case.

PMID- 7712099
TI  - Intramuscular myxoma of the face: an unusual localization. A clinicopathological
      study.
AB  - BACKGROUND: Intramuscular myxoma is a rare benign mesenchymal lesion. Only very
      rare cases of cutaneous localization of this tumor have been described, in
      particular related to the somatic soft tissues of the face. This unusual
      localization may clinically mimic nodular or cystic facial lesions having
      different origins. OBJECTIVE: The aim of our work was to well characterize the
      phenotype of the spindle cells characteristic of intramuscular mixoma. METHODS:
      Tissue samples were processed for morphological and ultrastructural studies.
      Moreover, immunohistochemical stainings were performed to characterize the
      expression of different nonmuscular and muscular cytoskeletal proteins. RESULTS:
      The tumor was composed of sparse spindle cells embedded in a prominent mucoid
      matrix. Besides the predominance of a fibroblast-like appearance, some neoplastic
      cells displayed immunohistochemical and ultrastructural features resembling
      either myofibroblasts or primitive mesenchymal cells, with a modulation of cell
      actin expression. CONCLUSION: The presence of multiple phenotypes of nonmuscular,
      mesenchymal pathway of differentiation can be considered a peculiar feature of
      intramuscular myxoma.

PMID- 7712100
TI  - Hypertrophic discoid lupus erythematosus resembling squamous cell carcinoma.
AB  - BACKGROUND: Hypertrophic discoid lupus erythematosus (HDLE) may resemble
      cutaneous squamous cell carcinoma (SCC) histologically. OBJECTIVE: The histologic
      features that help to differentiate HDLE from SCC are reviewed. METHODS: Two
      patients are described with HDLE. RESULTS: Both patients were treated initially
      with Mohs surgery for "biopsy-proven" SCC. Subsequent biopsies confirmed the
      diagnosis of HDLE and the patients responded well to appropriate therapy. No
      significant complications occurred in either patient. CONCLUSION: Lesions of HDLE
      may imitate SCC. Strategies are suggested to avoid surgical procedures based on
      an incorrect biopsy report.

PMID- 7712101
TI  - The hinged mucosal flap. A contour-saving approach to submucosal lesions of the
      lip.
AB  - BACKGROUND: A variety of approaches have been described for the removal of lip
      lesions, but approaches to submucosal lesions are not generally explored as a
      separate category of problem. A new adaptation of hinged tissue elevation
      occurred when vermilion mucosa was elevated, a small mucous membrane flap
      created, and then reapplied over a submucosal lip mass defect. OBJECTIVE:
      Presentation of a new application of hinged flaps, using lip mucosa as the flap
      tissue to be raised and reapplied to the underlying muscularis. The purpose of
      the technique was to preserve all tissue above the mass, while successfully
      removing the submucosal lesion. RESULTS: Application of the hinged mucosal flap
      concept to the lower lip resulted in complete preservation of the lip contour
      without invasion of the infravermilion shelf or subjacent chin areas, and without
      any anterior vermilion invasion. METHOD: The surgical technique of evolving a
      hinged mucosal lip flap is described, with multiple photographs demonstrating the
      serial maneuvers carried out. Surgical intervention resulted in complete
      obliteration of the benign lesion with essentially no visible scarring and no
      change in lip contour. CONCLUSION: Utilization of a hinged mucosal flap on the
      lip for removal of smaller submucosal lesions results in complete preservation of
      the delicate lip contours without sacrifice of subjacent lip tissue or visible
      scar beyond the vermilion junction. Further extension of the hinged flap
      principle to subepidermal exploration and extirpation elsewhere logically
      follows. Applying the principles of hinged flaps to lip submucosal lesions
      results in virtually undetectable surgical sequellae.

PMID- 7712102
TI  - Acquired posttransplantation hair kinking.

PMID- 7712103
TI  - Changes in shape and viability of cultured adult rabbit cardiac myocytes during
      ischemia/reperfusion injury.
AB  - The goal of this work was to define the distinction between irreversible
      structural changes and actual loss of cell viability during
      hypoxic/ischemic/reperfusion injury to one-day cultured adult rabbit cardiac
      myocytes. Myocytes were exposed to 5 mM NaCN and 20 mM 2-deoxyglucose (chemical
      hypoxia) or anoxia at pH 6.2 to simulate ischemia. Shortening and
      hypercontraction (cell rounding and blebbing) were monitored by bright field
      microscopy, and loss of viability was determined by nuclear labeling with
      propidium iodide. After both treatments, myocytes began to shorten after 30
      minutes, and most were hypercontracted after 3 hours. 50% loss of viability did
      not occur until after 6 hours or more. To simulate reperfusion, myocytes were
      washed with fresh aerobic buffer at pH 7.4. Loss of viability was accelerated
      when cells were reperfused with Krebs-Ringer solution. This cell killing was
      prevented when myocytes were reperfused with nutrient culture medium instead of
      Krebs-Ringer solution. Both contracted and hypercontracted cells partially
      relaxed after reperfusion. These results indicate that structural changes
      (contraction, hypercontraction and blebbing) to adult cardiac myocytes are
      distinct from outright cell death caused by plasma membrane failure. Persistence
      of cell viability suggests that rescue of cardiac myocytes from necrotic cell
      death may be possible even very late in injury.

PMID- 7712104
TI  - Ischemia/reperfusion injury is aggravated by an iron supplemented diet and is
      partly prevented by simultaneous antioxidant supplementation.
AB  - In humans high levels of storage iron as well as low iron binding capacity are
      considered risks for ischemic heart disease development. The aim of this study
      was to determine whether a diet containing iron to a concentration of the
      recommended upper limit alters the degree of myocardial ischemic/reperfusion
      injury on rats and whether simultaneous antioxidant supplementation had any
      effect. Results indicate that the iron supplemented diet increased the degree of
      oxidative injury while simultaneous antioxidant supplementation prevented much of
      this increase. The mechanism for this was probably an elevated hydroxyl radical
      production due to the enlarged transit iron pool.

PMID- 7712105
TI  - Salicylate in the perfusate during ischemia/reperfusion prevented mitochondrial
      injury.
AB  - Salicylate is widely used as a stable trap for the highly reactive hydroxyl
      radical. The purpose of this study was to determine whether the addition of
      salicylate to hearts subjected to ischemia and reperfusion was able to prevent
      some injury. Salicylate was able to inhibit mitochondrial damage, and preserved
      ascorbate and alpha-tocopherol depletion due to ischemia/reperfusion in rat
      hearts. It did not prevent the elevation of low molecular weight iron. We
      conclude that salicylate functions as an antioxidant and afforded protection
      against ischemia and reperfusion.

PMID- 7712106
TI  - Effect of acetaminophen on stress-induced gastric mucosal lesions in rats.
AB  - The effects of acetaminophen (APAP) on stress-induced gastric mucosal lesions
      were investigated in rats treated with water-immersion restraint stress (WIR) for
      3 hours. Three-hour WIR caused both significant increase in gastric lesions in
      terms of ulcer index and lipid peroxide levels and decrease in prostaglandin E2
      (PGE2) levels in the stomach, compared with prestress control levels. When APAP
      (500mg/kg) was intraperitoneally (i.p.) administered into rats 2 hours before
      WIR, the stress-induced changes were significantly inhibited. Whereas, three-hour
      WIR markedly decreased total glutathione levels in the liver, but not in the
      stomach and plasma and simultaneously reduced glutathione (GSH) levels in the
      liver and stomach were markedly decreased. In addition to the enhancement of
      decrease in liver total glutathione levels, APAP pretreatment caused significant
      decrease in gastric and plasma total glutathione levels compared with prestress
      control levels. Moreover, co-administration of indomethacin (5mg/kg, i.p.) with
      APAP almost abolished the protective effects of APAP against the stress-induced
      ulceration. These results suggest that APAP may protect gastric mucosa from
      stress-induced ulceration, probably through the promoted production of PGE2 in
      the gastric mucosa without restoring glutathione levels.

PMID- 7712107
TI  - Clenbuterol increases norepinephrine release from rat brain slices by a calcium-
      and receptor-independent mechanism.
AB  - Clenbuterol (10-100 microM), a beta 2-adrenergic agonist, potentiated basal
      (unstimulated) and electrical stimulation-evoked release of 3H-norepinephrine
      from cerebral cortical slices in a concentration-dependent manner. The beta
      adrenergic antagonists propranolol and ICI 118,551 did not antagonize the
      facilitatory effect of clenbuterol on basal 3H-norepinephrine efflux. Selective
      down-regulation of beta 2-adrenergic receptors produced by chronic administration
      of clenbuterol also did not alter this effect of in vitro clenbuterol, despite
      marked reductions in the density of these receptors. These results suggest that
      the increase in basal efflux of 3H-norepinephrine observed with clenbuterol was
      not mediated by beta 2-adrenergic receptors. The facilitatory effect of
      clenbuterol on basal 3H-norepinephrine efflux was Ca(2+)-independent, which may
      indicate an amphetamine-like mechanism of action. The enhanced basal efflux of 3H
      norepinephrine produced by clenbuterol was stereoselective; there was a four-fold
      increase in basal 3H-norepinephrine efflux with the (+)-isomer of clenbuterol
      compared with that induced by the (-)-isomer; this contrasts with the
      stereoselectivity of the isomers for interacting with beta 2-adrenergic
      receptors. The present results may explain some of the behavioral actions of
      clenbuterol, particularly those observed after long-term treatment, and may be
      relevant to the antidepressant actions of this compound.

PMID- 7712108
TI  - Species differences in the inhibiting effect of fluvastatin, a new inhibitor of
      HMG-CoA reductase, on cholesterol biosynthesis.
AB  - Cholesterol synthesis both ex vivo and in vivo in liver and ileum of hamsters was
      significantly inhibited by fluvastatin. This ex vivo inhibition was considerably
      lower in fluvastatin-treated hamsters than in fluvastatin-treated rats. In
      hamsters and rats, fluvastatin was more potent than pravastatin on inhibitory
      activities of sterol synthesis in liver, but not in the hamster ex vivo. This may
      indicate that, in part, the hydrophobicity of the fluvastatin molecule confers
      the selectivity and metabolism in the liver of hamsters and rats to originate
      from the species differences.

PMID- 7712109
TI  - Relationship between plasma levels of type II phospholipase A2, PAF
      acetylhydrolase, endothelin-1, and thrombomodulin in patients with infected
      burns.
AB  - The relations between type II phospholipase A2 (PLA2) and PAF acetylhydrolase
      (PAFAH) levels and those of endothelin-1 (ET-1) and thrombomodulin (TM) were
      examined in samples containing the maximum amount of TNF-alpha detected over the
      clinical course for each patient with burn wound infection. The study included 23
      patients with a total burn surface area of > 20%. Plasma levels of tumor necrosis
      factor-alpha (TNF-alpha), type II PLA2, PAFAH, TM, and ET-1 were 174.1 +/- 239.5
      pg/ml, 229.5 +/- 190.8 ng/ml, 22.68 +/- 7.07 nmol/min per ml, 6.62 +/- 2.78
      ng/ml, and 7.45 +/- 2.99 pg/ml, respectively. There were significant correlations
      between plasma levels of type II PLA2 and TM (r = 0.767, p < 0.0001), between
      PAFAH and TM (r = 0.542, p = 0.0076), between type II PLA2 and ET-1 (r = 0.688, p
      = 0.0003), and between PAFAH and ET-1 (r = 0.516, p = 0.0117). These results
      suggest that the increases in plasma type II PLA2 and PAFAH are related to
      vascular endothelial disorders in patients with infected burns.

PMID- 7712110
TI  - Anti-lipid A monoclonal antibodies and anti-LPS antiserum effects on limulus
      activity of LPS.
AB  - Anti-lipid A monoclonal antibodies (A78S1 and A523) and anti-LPS antiserum can
      decrease the mortality due to endotoxic shock in the newborn rat. However, in
      vitro LPS detoxification of anti-lipid A monoclonal antibodies is not known.
      Thus, we studied in vivo effects of A78S1 (IgG), A523 (IgM), and anti-LPS
      antiserum on Limulus activity. Anti-LPS antiserum decreased Limulus activity of
      S. enteritidis, E. coli and S. typhosa LPS. However, neither A78S1 nor A523
      decreased the Limulus activity of E. coli and S. typhosa LPS. A78S1 or A523
      incubation with S. enteritidis LPS at different doses (0.1 to 100 ng/ml) did not
      alter the Limulus activity. Perchloric acid treatment after LPS incubation with
      A78S1 or A523 significantly decreased Limulus activity. Therefore, antilipid A
      monoclonal antibodies (A78S1 and A523) can bind LPS, but do not decrease Limulus
      activity.

PMID- 7712111
TI  - The effect of spiroorthocarbonate volume modifier co-monomers on the in vitro
      toxicology of trial non-shrinking dental epoxy co-polymers.
AB  - A major improvement in dental restoratives is possible through the development of
      biomaterials that do not shrink upon polymerization, hence, avoid leakage and
      subsequent breakdown. Polymers containing spiroorthocarbonates (SOCs) show
      promise in this respect, but their toxicology in copolymerized materials has not
      been explored. In this study, the in vitro toxicology of these materials in
      homopolymer form and in two trial non-shrinking epoxy co-polymers was evaluated
      for cytotoxicity and mutagenicity. Cytotoxicity was determined by the MTT test to
      measure the lethality effect on mouse L929 cells. Mutagenicity was evaluated
      using the Ames-Salmonella Test. For comparison, commercial composite and adhesive
      materials as well as several other materials of current interest in dentistry
      were also evaluated. Epoxy resin samples containing 5% of either T/T SOC or Dp
      SOC reduced the cytotoxicity (TC50) from approximately 400 to 800 micrograms/200
      microliters. The epoxy-spiro copolymers had more favorable TC50 values than the
      commercial product Super-Bond. They showed TC50 values on the order of 35%
      greater than Super-Bond and 45% less than Scotchbond 2, the latter two being
      materials currently used in the clinic. These two comparatives demonstrated dose
      response curves with lower doses at maximum cell kill values than the spiro
      materials. The epoxy formulations all showed weak mutagenesis, but this is
      attributed to the epoxy formulation and not the SOCs. Although considerable
      toxicology is yet be conducted, these in vitro results suggest that biocompatible
      copolymer formulations for spiroorthocarbonates are a developmental reality.

PMID- 7712112
TI  - Styrene-induced hepatotoxicity in mice depleted of glutathione.
AB  - In mice depleted of glutathione (GSH) by pretreatment with an inhibitor of GSH
      synthesis, buthionine sulfoximine (BSO; 1 hr before styrene, 2 mmol/kg or higher
      doses, ip), styrene (0.96-5.76 mmol/kg, po) produced hepatotoxicity characterized
      by an increase in serum alanine transaminase activity and cetrilobular necrosis
      of hepatocytes. Treatment with inhibitors of hepatic cytochrome P-450-dependent
      monooxygenases such as carbon disulfide, methoxsalen, piperonyl butoxide, and SKF
      525A prevented or tended to reduce the hepatotoxic effect of styrene given in
      combination with BSO. Styrene 7,8-oxide (3.84 mmol/kg, po), a known metabolite of
      styrene, in combination with BSO caused an earlier and larger increase in SALT
      than that caused by an equimolar dose of styrene in combination with BSO. These
      results suggest that metabolism of styrene, possibly to styrene 7,8-oxide, is a
      necessary step in styrene-induced hepatotoxicity in GSH-depleted mice. Before the
      onset of hepatotoxicity, styrene in combination with BSO produced a larger and
      more prolonged depletion of hepatic GSH than that seen after the sole treatment
      with BSO or prolonged depletion of hepatic GSH than that seen after the sole
      treatment with BSO or styrene, but no depletion of hepatic protein sulfhydryls
      was induced by styrene in combination with BSO.

PMID- 7712113
TI  - Selective increase in expression of isoform PP1 gamma 1 of type-1 protein
      phosphatase in chondrosarcoma cells.
AB  - The expression of the two catalytic subunits of protein phosphatase (PP) type 1
      PP1 gamma 1 and PP1 delta was examined in 4 cases of osteochondroma and 4 cases
      of enchondroma as a benign cartilaginous tumor, and 4 cases of chondrosarcoma as
      a malignant cartilaginous tumor using immunohistochemical analysis. The
      percentage of tumor cells stained positively with antiserum against PP1 catalytic
      subunit isoform PP1 gamma 1 were significantly higher in chondrosarcoma than in
      osteochondroma and enchondroma. Furthermore, chondrosarcoma showed markedly high
      S-phase fraction in the cell cycle of tumor cells, as compared to osteochondroma
      and enchondroma. These results suggest that PP1 gamma 1 is involved in the
      accelerated growth of malignant cells in chondrosarcoma.

PMID- 7712114
TI  - Linkage analysis between manic depressive illness and the region on chromosome
      12q involved in Darier's disease.
AB  - Co-segregation between Darier's disease and manic depressive illness has been
      reported. A gene causing Darier's disease has recently been mapped to chromosome
      12q23-q24.1, and this region may thus be considered a candidate region
      potentially containing a gene involved in the aetiology of manic depressive
      illness. At least one possible candidate gene for manic depressive illness, pro
      melanin-concentrating hormone, is located on chromosome 12q23-q24. The present
      study investigated linkage between manic depressive illness and this region on
      chromosome 12q, using three microsatellite polymorphisms as genetic markers which
      flank the gene causing Darier's disease. For all dominant models close linkage
      was excluded. For broader phenotypic models linkage was excluded in the interval
      between markers, even in one large family alone.

PMID- 7712115
TI  - Lack of association of the dopamine D3 receptor gene polymorphism (BalI) in
      Chinese schizophrenic males.
AB  - Dopamine receptors have been implicated in the aetiology of schizophrenia and
      mode of action of antipsychotic drugs. A finding of increased homozygosity at the
      D3 receptor gene (BalI locus) has recently been reported. We have investigated
      the distribution of D3 receptor gene polymorphism (BalI) in 137 schizophrenic
      Chinese males and 125 healthy matched controls. The frequency of the rare allele
      was 0.30 and 0.31 in the patient and the control series. The distribution of
      genotypes in the patient series did not deviate significantly from Hardy-Weinberg
      equilibrium in the present series.

PMID- 7712116
TI  - A multivariate analysis of repeated measures: linkage of the albinism gene (Tyr)
      to a QTL influencing ethanol-induced anesthesia in laboratory mice.
AB  - We propose the use of multivariate analysis of variance in order to address
      linkage relationships between a genetic marker and a phenotype that is specified
      by multiple variables. Moreover, enhanced power of a linkage model that
      simultaneously accounts for environmental factors is demonstrated in the present
      study. This strategy was used to establish linkage of a quantitative trait locus
      influencing ethanol-induced anesthesia to the albinism gene (Tyr) in mouse. This
      approach, which can be implemented immediately with most statistical packages,
      provides the extreme flexibility of multivariate analysis of variance for
      analyzing complex questions of linkage regarding either animal or human research
      paradigms.

PMID- 7712117
TI  - Analysis of the conserved Asp(114) residue of the dopamine D2 receptor in
      schizophrenic patients.
AB  - The factors that influence response to antipsychotics treatment in chlorpromazine
      remain difficult to delineate but are thought to include genetic factors. Site
      directed mutagenesis studies have demonstrated that substitution of the conserved
      residues Asp(113) to an Asn or Glu greatly reduces the binding affinity of
      propranolol in the beta-adrenergic receptor and the substitution of an Asp(114)
      has similar effects in the dopamine D2 receptor. In this study we have found the
      Asp(114) in the dopamine D2 receptor to be unaltered in 72 unrelated
      schizophrenic individuals including 12 patients classified according to their
      response to chlorpromazine.

PMID- 7712118
TI  - An association study of debrisoquine hydroxylase (CYP2D6) polymorphisms in
      schizophrenia.
AB  - The cytochrome P450 mono-oxygenases are a group of enzymes that metabolize a
      variety of exogenous and endogenous compounds, some of which are potentially
      toxic. Individual variations in the metabolism of potential toxins could
      influence susceptibility to disorders having genetic and environmental
      components, such as schizophrenia. The frequency of two common mutant alleles of
      the gene for the cytochrome P450 enzyme debrisoquine-4-hydroxylase (CYP2D6) was
      determined in 264 Caucasian schizophrenic patients and 217 controls, using the
      polymerase chain reaction and restriction enzyme digestions. The patient and
      control samples showed no significant deviation from Hardy-Weinberg equilibrium
      and the frequency of each mutant allele (CYP2D6A and CYP2D6B) did not differ
      between patients and controls.

PMID- 7712119
TI  - The Marfan syndrome gene locus as a favoured locus for susceptibility to
      schizophrenia.
AB  - Marfan syndrome (MS) is a rare autosomal dominant disorder of connective tissue
      with manifestations in the cardiovascular, ocular and skeletal systems. Genetic
      linkage analysis with random probes has mapped the MS locus to 15q21.1. There
      have been several reports of Marfan syndrome co-segregating with schizophrenia
      within families, which suggest that a common genetic factor may be shared between
      schizophrenia susceptibility and MS. This could be due to a cytogenetic
      abnormality affecting both genetic loci or due to co-segregation of two disease
      loci near each other on the same chromosome. We tested this hypothesis by using
      genetic linkage analysis with multiplex families. Using three genetic markers
      spanning the MS locus, we were unable to find evidence of linkage with
      schizophrenia across the Marfan syndrome locus on chromosome 15.

PMID- 7712120
TI  - No major role for the dopamine D2 receptor Ser-->Cys311 mutation in
      schizophrenia.
AB  - A new structural polymorphism (Ser311/Cys311) in the dopamine D2 receptor (DRD2)
      gene has recently been reported to be associated with schizophrenia, particularly
      in patients with a positive family history of schizophrenia (Arinimi et al.,
      1994). However these findings remain controversial (Asherson et al., 1994; Nanko
      et al., 1994; Nothen et al., 1994; Shaikh et al., 1994). Thus we investigated the
      role of the Cys311 mutation in schizophrenia using both association and family
      studies. First, we screened for the Cys311 mutation in 113 unrelated Caucasian
      schizophrenics (mean age 42 +/- 0.6; 34 females and 79 males) including 25
      familial cases, and 184 unrelated controls (mean age 49 +/- 0.5, 74 females and
      110 males) free of any psychiatric disorders. Diagnoses were ascertained
      according to DSM-III criteria (Campion et al., 1994). All patients and controls
      were native to the area of Rouen.

PMID- 7712121
TI  - Peptidomimetic antagonists designed to inhibit the binding of CD4 to HIV GP120.
AB  - Attempts to enhance the efficacy of our previously reported CD4 CDR2-like
      (residues 40-45) mimetic 1 by incorporation of the critical guanidine residue Arg
      59 of CD4 are described.

PMID- 7712122
TI  - Design of orally bioavailable, symmetry-based inhibitors of HIV protease.
AB  - A series of novel inhibitors of HIV-1 protease with excellent oral
      bioavailability is described. Differential acylation of the two amino groups of
      symmetry-based diamine core groups 2-5 led to unsymmetrically substituted
      inhibitors 17-43, many of which inhibited HIV protease at subnanomolar
      concentrations. Anti-HIV activity in vitro was observed at 0.1-1 microM. A
      systematic evaluation of the pharmacokinetic behavior of these inhibitors in rats
      identified the influence of aqueous solubility, molecular size and hydrogen
      bonding functionality. Compound 30 (A-80987) was selected for further evaluation
      based on a favorable Cmax/ ED50 ratio (> 20) and half-life (> 2 h).

PMID- 7712123
TI  - Synthesis, antiviral activity, and bioavailability studies of gamma-lactam
      derived HIV protease inhibitors.
AB  - Incorporation of a gamma-lactam in hydroxyethylene isosteres results in modest
      inhibitors of HIV-1 protease. Additional structural activity studies have
      produced significantly more potent inhibitors with the introduction of the
      trisubstituted cyclopentane (see compound 20) as the optimum substituent for the
      C-terminus. This new amino acid amide surrogate can be readily prepared in large
      scale from (R)-pulegone. Optimized compounds (36) and (60) are potent antiviral
      agents and are well absorbed (15-20%) in a dog model after oral administration.

PMID- 7712124
TI  - Design of orally active, non-peptide fibrinogen receptor antagonists. An
      evolutionary process from the RGD sequence to novel anti-platelet aggregation
      agents.
AB  - The evolutionary process from the Arg-Gly-Asp-Phe (RGDF) tetrapeptide to potent
      orally active anti-platelet agents is presented. The RGD sequence is an important
      component in the recognition of fibrinogen by its platelet receptor GP IIb-IIIa
      (integrin alpha IIb beta 3). This work concentrates on the replacement of the Arg
      Gly dipeptidyl fragment by an acylated aminobenzamidine. The C-terminal fragment
      has been replaced by a variety of beta-amino acids, expanding on a previously
      reported paradigm. The lead compounds showed good potency in an in vitro platelet
      aggregation assay (dog PRP/ADP). The affinity for the fibrinogen receptor was
      confirmed in several cases by the ability to inhibit 125I fibrinogen binding to
      activated human platelets. The ethyl ester prodrug form was tested by oral
      administration to dogs and monitoring of the anti-platelet effect on ex vivo
      collagen induced platelet aggregation. From the structural studies reported, the
      4-[[(aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid (5) was the best surrogate
      for the Arg-Gly dipeptide. Several conformationally restricted analogues are also
      reported which are compatible with the hypothesis of RGD binding to the alpha IIb
      beta 3 in a turn-extended-turn conformation. The structure-activity relationships
      described also underline the importance of the beta-amino acid substitution for
      potency. In particular, the absolute configuration at the beta-carbon was crucial
      for high affinity. The best acid/ester pairs reported in this study had high
      potency (acid PRP/ADP IC50 approximately 50 nM) and showed good oral activity in
      dogs at 5 mg/kg per os (ethyl ester).

PMID- 7712125
TI  - Design of a potent and orally active nonpeptide platelet fibrinogen receptor
      (GPIIb/IIIa) antagonist.
AB  - The direct design of the potent nonpeptide platelet fibrinogen receptor
      (GPIIb/IIIa) antagonist, 8-[[[4- (aminoiminomethyl)phenyl]amino]carbonyl]-2,3,4,5
      tetrahydro-3-oxo- 4- (2-phenylethyl)-1H-1,4-benzodiazepine-2-acetic acid, (3) (SB
      207448), based on the structure and conformation of the potent and highly
      constrained cyclic peptide antagonist SK&F 107260 (2), has been reported [Ku et
      al., J. Am. Chem. Soc. 1993, 115, 8861]. While 3 displayed in vivo activity in
      the conscious dog following intravenous administration, it was not active
      following intraduodenal administration; activity was measured with an ex vivo
      platelet aggregation assay. The secondary amide in 3 was N-methylated in the
      expectation of increased absorption and bioavailability. The resulting tertiary
      amide, 4 (SB 208651), also showed high binding affinity for human GPIIb/IIIa and
      potent antiaggregatory activity in human platelet-rich plasma. Most importantly,
      4 was active in vivo following intravenous and intraduodenal administration.
      Comparison of the iv and id inhibition curves suggests an apparent
      bioavailability of approximately 10%. Thus, 4 represents the first orally active
      compound in this series of potent, nonpeptide fibrinogen receptor antagonists.

PMID- 7712126
TI  - Renin inhibitor SC-51106 complexed with human renin: discovery of a new binding
      site adjacent to P3.
AB  - SC-51106, a 'minimal-size' diol-based renin inhibitor lacking a P4 residue, has
      been co-crystallized with human renin and the structure of the complex determined
      by X-ray crystallography. This study defines the mode of binding of this
      important class of renin inhibitor, and in conjunction with molecular modeling,
      has led to the discovery of a new binding site adjacent to S3, which is termed
      the 'S3aux(iliary)' subsite.

PMID- 7712128
TI  - Renin inhibitors: C-terminal oxetanes as potent transition-state mimics.
AB  - A novel transition-state mimic containing a C-terminal oxetane has been
      developed. Renin inhibitors incorporating this fragment exhibit enhanced potency
      against human plasma renin at physiological pH. The binding affinity of this new
      species has allowed size reductions at other sites.

PMID- 7712127
TI  - HIV-1 protease inhibitors: ketomethylene isosteres with unusually high affinity
      compared with hydroxyethylene isostere analogs.
AB  - HIV protease is a member of the aspartic proteinase family of proteolytic enzymes
      which include pepsin and renin. In contrast to the enhanced affinity seen with
      renin and pepsin upon conversion of the transition-state isostere, ketomethylene,
      to the hydroxyethylene, a set of HIV protease inhibitors showed a reduction in
      affinity. This implies that interactions with the active site of other segments
      of the inhibitor than those of the transition-state analog must predominate in
      the case of HIV protease, and that observations made on mammalian aspartic
      proteinases do not necessarily apply to viral aspartic proteinases.

PMID- 7712129
TI  - Synthesis and biological activity of ras farnesyl protein transferase inhibitors.
      Tetrapeptide analogs with amino methyl and carbon linkages.
AB  - Replacement of the central amino methylene linkage of C[psi CH2NH]A[psi CH2NH]AX
      tetrapeptide inhibitors with carbon tethers led to compounds with potency in the
      nanomolar range. Some of the more potent olefinic compounds inhibit Ras
      processing in intact v-ras transformed NIH 3T3 cells with IC50 values in the 0.1
      to 1 microM range, and inhibit selectively the anchorage-independent growth of H
      ras transformed Rat1 cells at 10 microM.

PMID- 7712131
TI  - Herpes simplex virus ribonucleotide reductase subunit association inhibitors: the
      effect and conformation of beta-alkylated aspartic acid derivatives.
AB  - Incorporating beta-alkylated aspartic acid derivatives into herpes simplex virus
      ribonucleotide reductase subunit association inhibitors can improve inhibitor
      potency up to 50 times over the corresponding inhibitors containing an
      unsubstituted aspartic acid. A combination of NMR studies, conformational
      analysis, and molecular mechanics calculations suggests that the beta-alkyl group
      improves inhibitor potency by favoring the bioactive conformation of the critical
      aspartic acid carboxyl group. Further support for this hypothesis is provided by
      a potent conformationally restricted aspartic acid derivative in which the
      carboxyl group is locked in the putative bioactive conformation.

PMID- 7712130
TI  - Benzodiazepine peptidomimetic inhibitors of farnesyltransferase.
AB  - A structural survey of protein Zn2+ binding geometries was instigated based upon
      the functional requirement of Ras farnesyltransferase for Zn2+. The Cys-X-X-Cys
      motif found in Zn(2+)-binding proteins such as aspartate transcarbamylase was
      used as a template to devise a bidentate-coordination model for Cys-A1-A2-X
      peptide inhibitors. Accordingly, replacement of the central dipeptide with the
      hydrophobic scaffold 3-amino-1-carboxymethyl-2,3-dihydro-5- phenyl-1H-1,4
      benzodiazepin-2-one (BZA) yielded a peptidomimetic inhibitor, Cys(BZA)Met, of
      moderate potency (IC50 = 400 nM). N-Methylation of the cysteine amide improved
      potency almost 100-fold (IC50 = 0.3-1 nM). The increased affinity presumably
      correlates with a preferred conformation of the inhibitor which maximizes a
      hydrophobic interaction between the scaffold and the enzyme, and the proper
      presentation of cysteine and methionine to allow bidentate coordination at Zn2+.
      These non-peptide inhibitors have been shown to block farnesylation of the Ras
      protein in intact cells and provide lead compounds for the development of new
      cancer therapeutic agents.

PMID- 7712132
TI  - Conformationally constrained o-tolylpiperazine camphorsulfonamide oxytocin
      antagonists. Structural modifications that provide high receptor affinity and
      suggest a bioactive conformation.
AB  - A series of new o-tolylpiperazine camphorsulfonamide OT antagonists is described.
      Analogs containing conformationally constrained 1-acylamino-2-propyl substituents
      at the camphor C2 endo position exhibit high affinity for OT and AVP-V1a
      receptors or high affinity and selectivity for OT receptors, depending on
      functionalities present in the acyl group. Determination of the preferred
      conformation of potency-enhancing 1-acylamino-2-propyl substituents using
      molecular mechanics energy calculations and X-ray crystallography, along with
      topological similarities to a conformationally constrained cyclic hexapeptide OT
      antagonist, suggests a receptor-bound conformation for this series of non-peptide
      OT antagonists.

PMID- 7712133
TI  - Selective non-peptide ligands for an accommodating peptide receptor.
      Imidazobenzodiazepines as potent cholecystokinin type B receptor antagonists.
AB  - A series of imidazobenzodiazepines, non-peptide antagonists of the peptide
      hormone cholecystokinin (CCK), are described. Derived by chemical modification of
      the benzodiazepine ring system embedded within the CCK-B antagonist L-365,260,
      these compounds display CCK-B/CCK-A selectivity and some analogs have receptor
      binding affinities in the subnanomolar range. This group of novel
      imidazobenzodiazepines, among which N-[(2S,4R)-methyl-6-phenyl-2,4-dihydro-1H
      imidazo[1,2- alpha][1,4]benzodiazepin-4-yl]-N'-[3-methylphenyl]-urea (12) is the
      principal compound, expands the structural diversity of the collection of non
      peptide CCK-B antagonists and will be useful in further delineating the function
      of CCK in the central nervous system.

PMID- 7712134
TI  - Amino acids that specify structure through hydrophobic clustering and histidine
      aromatic interactions lead to biologically active peptidomimetics.
AB  - Acyclic beta-sheet structure can be nucleated in heptapeptides when the 4-(2
      aminoethyl)-6-dibenzofuranpropanoic acid residue (1) is flanked in sequence by
      two His residues, a His residue and a hydrophobic residue or by two hydrophobic
      residues. Acyclic beta-sheet peptidomimetics having an appropriate sequence have
      sufficient structural integrity to exhibit antimicrobial activity equivalent to
      that of gramicidin S.

PMID- 7712135
TI  - Anaerobic biodegradability testing of surfactants.
AB  - Anionic and nonionic surfactants (5-50 mg C/g solids/L medium) were screened for
      anaerobic microbial decomposition to methane in an automated pressure transducer
      serum bottle assay system at 35C using municipal digester solids as a source of
      anaerobic bacteria. Analysis of the headspace gas recovered from tests with
      linear primary alcohol sulfates (A45S and A24S) and a linear alcohol ethoxylate
      (LAE-8) showed that these compounds were readily degraded (60-85% of the
      theoretical methane, TM) after a 15-30 day lag period at 50 ppm C. The extent of
      degradation of a branched alkyl phenol ethoxylate (NPE-9) was lower (30-40% TM).
      A survey of intact nonionic and anionic surfactants present in municipal digester
      sludges in the U.S. showed that these materials were present at levels of 0.5-8
      mg CTAS or MBAS/g dry solids. A surfactant which was slower to biodegrade (NPE-9)
      at 50 ppm C was readily metabolized to methane when tested at 5 and 10 mg C/g
      solids/L. The pressure transducer serum bottle method described may be used to
      test biodegradability and inhibitory effects on methanogenesis at surfactant
      concentrations (e.g. 5 ppm C/g solids) typically present in digesters.

PMID- 7712136
TI  - Biodegradation studies of hydrocarbons in soils by analyzing metabolites formed.
AB  - Microbial degradation of diesel fuel and lubricating oil was studied in
      artificial soils. Soon after 1 week and until the end of the study (25 weeks)
      organic acids and ketones which were not original components of the oils
      contaminating the soil samples were identified. Predominantly alicyclic and
      branched-chain aliphatic organic acids as well as diacids and aromatic ketones
      were formed by degradation. Further degradation of these alicyclic acids was
      observed. Similar oxidized products were also identified in actual contaminated
      soils.

PMID- 7712137
TI  - Comparison of multi-media transport and transformation models: regional fugacity
      model vs. CalTOX.
AB  - Two multimedia environmental transport and transformation computer models are
      summarized and compared. The regional fugacity model published by Mackay and
      Paterson (1991), termed Fug3ONT, is a four compartment steady-state model
      designed to simulate the relative distribution of nonionic organic chemicals in a
      multimedia system. CalTOX is a seven compartment multimedia total exposure model
      for hazardous waste sites. Both models are based on the principles of fugacity.
      CalTOX, however, separates the soil into three layers (surface, root, and vadose)
      and uses a different approach to estimate the diffusive mass transfer rate in
      soil. These differences result in lower estimates of the steady-state contaminant
      concentrations of six environmentally relevant chemicals in the root soil of
      CalTOX as compared to the bulk soil of Fug3ONT. The difference is greatest for
      compounds with low mobility in soil such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin
      and Benzo(a)pyrene where estimates from CalTOX and Fug3ONT differ by more than 3
      orders of magnitude. Otherwise, the models provide similar estimates for the
      distribution of the six chemicals among the air, water, sediment and surface
      soil.

PMID- 7712138
TI  - The genotoxicity of substituted nitrobenzenes and the quantitative structure
      activity relationship studies.
AB  - The genotoxicity of 22 substituted nitrobenzenes was evaluated by the chromosome
      aberrations test in cultured human peripheral lymphocytes. 18 of 22 compounds
      exhibit genotoxic activities. A quantitative structure-activity relationship
      model was established to correlate the genotoxicity of substituted nitrobenzenes
      and the characteristics of the substituents on the benzene ring.

PMID- 7712139
TI  - In vivo evidence for a defect in the dopamine DA1 receptor in the prehypertensive
      Dahl salt-sensitive rat.
AB  - A defective dopamine DA1 receptor has been suggested to be involved in the salt
      sensitive hypertension in Dahl-S rats (DS). To investigate the consequences of
      this defect, the influence of DA1 receptor blockade (SCH23390) and of dopamine
      synthesis inhibition (benserazide) on volume expansion (VE)-induced sodium and
      dopamine excretion was studied in anesthetized prehypertensive DS and salt
      resistant Dahl rats (DR). Under control conditions all measured variables were
      equal in DR and DS. During VE (5% of BW), sodium and dopamine excretion increased
      similarly in the two strains. During peak natriuresis mean arterial blood
      pressure was 119 +/- 3 and 122 +/- 3 mm Hg, respectively. In DR treated with
      SCH23390, sodium excretion was only 72% of that in vehicle-treated DR. Dopamine
      excretion increased, however, as in vehicle-treated DR. In DS, treatment with
      SCH23390 did not attenuate natriuresis and dopamine excretion also increased as
      in vehicle-treated DS. In benserazide-pretreated DR and DS, sodium excretion
      during VE was similar, but only 50-51% of that in the respective vehicle-treated
      group. Dopamine excretion decreased by about 80% in both strains. In conclusion,
      prehypertensive DR and DS have a similar capacity to acutely excrete an
      intravenous saline load and to generate dopamine. The total dopamine involvement
      in VE-induced natriuresis is also comparable in the two strains, but the
      natriuresis mediated by DA1 receptors is pronounced in DR and non-existent in
      DS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712140
TI  - Angiotensin II induces hypertrophy and hyperplasia in adult human mesangial
      cells.
AB  - Several experimental studies point to a potential role of angiotensin II (Ang II)
      in the progression of glomerulosclerosis even in the absence of glomerular
      hypertension. We tested the hypothesis that Ang II acts as a growth factor for
      adult human mesangial cells (AHMC). AHMC were isolated from noninvolved parts of
      tumor nephrectomy specimens and grown in RPMI medium with the addition of fetal
      calf serum (FCS). All studies were performed with growth-arrested cells.
      Proliferation studies were done in serum-free standard growth medium (SF) with
      the addition of either various concentrations of insulin, plasma-derived serum,
      or FCS. Ang II (10(-10) to 10(-6) M) dose dependently increased the 3H-thymidine
      uptake of AHMC up to 57 +/- 13% over solvent controls (p < 0.01). In parallel,
      the DNA content was 36 +/- 10% higher (p < 0.05) than in solvent controls after 2
      days of culture. The cell numbers were higher up to 47 +/- 8% in Ang II (10(-6)
      M) stimulated cultures after 4 days of incubation (p < 0.01). The effect of Ang
      II was specific, since it was almost completely obliterated by the AT1 receptor
      antagonist DuP753. The effect of Ang II was particularly marked when cultures
      were incubated with SF plus high concentrations (1.7 x 10(-6) M) of insulin or SF
      plus 10% plasma-derived serum. In contrast, the effect was not significant when
      cultures were incubated with SF plus 10% FCS. Ang II, when added to platelet
      derived growth factor at various concentrations, did not further increase the
      proliferation. The effect on protein synthesis was assessed in growth-arrested
      AHMC by 3H-methionine uptake and protein/DNA ratio in cell lysates. Ang II (10(
      10) to 10(-6) M) dose dependently increased the 3H-methionine uptake of AHMC up
      to 47 +/- 10% over solvent controls (p < 0.01). In parallel Ang II (10(-8) to 10(
      6) M) dose dependently increased the 3H-methionine uptake of the protein/DNA
      ratio by 24 +/- 6% after 48 h of incubation. DuP753 obliterated the stimulatory
      effect of Ang II. Ang II (10(-6) M) also increased the mRNA of the immediate
      early growth-related gene Egr-1. We conclude that Ang II induces hypertrophy and
      proliferation in adult human mesangial cells. This result is of interest with
      respect to a potential role of Ang II in the pathogenesis of glomerulosclerosis
      in humans.

PMID- 7712141
TI  - Rat mesangial cells have a selective role in macrophage recruitment and
      activation.
AB  - In proliferative glomerulonephritis glomeruli are the target of an inflammatory
      reaction involving macrophage recruitment and activation. We examined the role of
      mesangial cells in this process. Supernatants from basal, IL-1, IFN-tau or LPS
      stimulated rat mesangial cells (MCS) were tested for chemotactic, colony
      stimulating and activation effects on macrophages in vitro. IL-1-stimulated MCS
      produced a macrophage chemoattractant (p = 0.007 compared with basal MCS) and MCP
      1 mRNA was detected in IL-1-stimulated mesangial cells. LPS or IL-1-stimulated
      MCS produced colony-stimulating activity (LPS p < 0.05, IL-1 p < 0.01, compared
      with basal MCS or control supernatant, CS). Macrophage activation, assessed by
      nitric oxide generation, was suppressed. This evidence from functional bioassays
      supports a selective role for mesangial cells in the control of macrophage
      induced glomerular injury, whereby activated mesangial cells participate in the
      recruitment and proliferation of infiltrating macrophages, and suppresses at
      least one field of macrophage activation, namely nitric oxide generation.

PMID- 7712142
TI  - In situ hybridization of type I collagen mRNA in puromycin aminonucleoside
      induced glomerulosclerosis.
AB  - In puromycin aminonucleoside (PAN)-induced focal glomerulosclerosis (FGS), the
      accumulation of type I collagen has been reported to be observed
      immunohistochemically in the sclerotic area. The present study was designed to
      identify the cell type involved in the synthesis of type I collagen in
      glomerulosclerosis. Tissue sections obtained from rat kidneys with PAN-induced
      FGS were hybridized with digoxigenin-labeled alpha 1(I) collagen anti-sense and
      sense cRNA probes. Hybridization signals of alpha 1(I) collagen mRNA were mainly
      detected in adhesive lesions on the glomerular capillary loop, suggesting that
      alpha 1(I) collagen mRNA-positive cells were visceral or parietal epithelial
      cells and did not have a mesangial distribution. Signals were also detected in
      interstitial cells. The alpha 1(I) collagen mRNA expression, however, was not
      observed in ED-1-positive cells. It is likely that intrinsic glomerular cells and
      interstitial cells, but not macrophages, synthesize type I collagen in sclerotic
      glomeruli.

PMID- 7712143
TI  - Antineutrophil cytoplasmic antibody-positive sera inhibit candidacidal activity
      of granulocytes.
AB  - Antineutrophil cytoplasmic antibodies (ANCA) are suspected of being involved in
      the pathogenesis of tissue injury in systemic vasculitis. We have investigated
      the effect of 10 sera from 8 patients with ANCA-associated diseases on the
      capacity of neutrophils derived from healthy persons to kill ingested Candida
      albicans. ANCA-containing sera inhibited candidacidal activity by 55-80% in
      comparison to control sera. This phenomenon could lead to the depression of
      antimicrobial resistance of patients with ANCA and could be involved in the
      pathogenesis of granuloma formation.

PMID- 7712144
TI  - Evaluation of the tubuloglomerular feedback system in human subjects.
AB  - It has been shown in animals that GFR decreases after administration of a
      carbonic anhydrase inhibitor (CAI) because of activation of the tubuloglomerular
      feedback. However, the magnitude of this response has never been studied in
      healthy subjects, nor has the possibility of inhibiting tubuloglomerular feedback
      with frusemide (FRU). Changes in CCr, V, CNa, CCl, CH2O, CLi were studied before
      and after acute administration of acetazolamide (ACZ) to 11 normal subjects or
      FRU to 9 normal subjects. Both ACZ and FRU increased V, CNa, CCl and CLi. Only
      FRU decreased CH2O. ACZ but not FRU decreased CCr, despite lesser increases of V,
      CLi and CH2O+CCl (rough indexes of distal delivery). The magnitude of the GFR
      decrease after comparable increases in distal delivery varied greatly between
      subjects. There was a tendency for the subjects with lower basal GFRs to show
      tubuloglomerular feedback responses of lesser magnitude than those with higher
      GFRs. These results show that it is possible to study tubuloglomerular feedback
      and its sensitivity in humans using CAIs. FRU blocks the tubuloglomerular
      feedback response. Its sensitivity appears to vary widely in normal subjects.

PMID- 7712146
TI  - Broca's aphasia: a syntactic and/or a morphological disorder? A case study.
AB  - The patient described here suffers from Broca's aphasia without a comprehension
      disorder. She is unique, since she has two speech styles available and she shifts
      between them spontaneously. One style is characterized by a mild syntactic
      disorder and the other by a quite severe morphological and syntactic disorder.
      None of the current theories about the underlying disorder in Broca patients
      without comprehension deficits can account for the fact that two linguistically
      different speech styles can occur in one patient, except the adaptation theory.
      It will be argued that both styles can be explained by the assumption of an
      impairment to the grammatical encoder (a processor which transforms the preverbal
      message into a surface structure, Levelt, 1989). This view suggests that the
      distinction between syntactic and morphological agrammatism could be a matter of
      strategy, rather than of impairment.

PMID- 7712145
TI  - Clusterin and the kidney.

PMID- 7712147
TI  - On the notion of a "subtle phonetic deficit" in fluent/posterior aphasia.
AB  - Phonetic investigations in the past decade or so have reported instances of a
      "subtle phonetic deficit" in the fluent aphasias, thereby challenging the
      traditional dichotomy of a motoric deficit characterizing the nonfluent aphasias
      and a selection deficit characterizing the fluent aphasias. This paper critically
      reviews the acoustic, physiological, and perceptual studies which have attempted
      to examine this phenomenon. These investigations have been evaluated in terms of
      differences in subject populations, task demands, subjects' performance, and
      problematic interpretations. Suggestions are offered for an experimental design
      which can help us operationalize this term and help us to better understand the
      speech production deficit in fluent aphasic patients.

PMID- 7712148
TI  - Event-related potential and behavioral correlates of semantic processing in
      Alzheimer's patients and normal controls.
AB  - In normal young adults, N400 amplitude varies inversely with the extent to which
      a word has been primed by its preceding semantic context. Based on a series of
      behavioral studies, it appears that in Probable Alzheimer's patients (PAD) the
      organization of semantic memory is disrupted such that specific items within a
      category lose their distinction, although superordinate information remains
      relatively intact. The present study examined whether the N400 gradient which has
      been found with normal young adults would also reflect this loss of
      discriminability among semantically related items in PAD patients. Ten normal
      young adults, 10 normal elderly, and 6 "mild" PAD patients made speeded (but
      accurate) sense/nonsense decisions to the terminal words of a series of highly
      constrained sentence contexts. The terminal words belonged to one of four
      stimulus types which varied as a function of relatedness to a highly expected
      word. Counter to our predictions, N400 amplitude was identically responsive to
      semantic relatedness in the young normal and PAD groups, but was characterized
      differently in the normal elderly. Given the significantly greater number of
      errors committed by PAD patients, we concluded that their disruption in semantic
      processing occurs at some point between the elicitation of N400 and the
      generation of the reaction time response. The anomalous N400 pattern in the
      normal elderly appeared to be strategy related and superimposed upon an otherwise
      normal semantic network.

PMID- 7712149
TI  - Aphasic and parkinsonian signing: differences in phonological disruption.
AB  - Since movements of the articulators in sign, unlike in speech, are directly
      observable, we can investigate signing not only as linguistic behavior but also
      as motor behavior and directly contrast linguistic-representational and motor
      execution disorders of signing. We compared the temporal sequencing
      characteristics (duration of segments, pausing, periods of change in handshape
      posture), intactness of distinctive features, and correct use of prosodic
      templates in three pairs of signers--two Deaf aphasic signers with posterior
      damage in the left hemisphere, two signers with Parkinson's disease, and two
      gender- and age-matched control signers. With respect to distinctive features,
      the aphasic signers exhibited selection errors in the American Sign Language
      (ASL) distinctive features system, while the Parkinsonian signers showed an
      intact distinctive feature inventory, but with disturbances in executing these
      features. The Parkinsonian signers, unlike the aphasic and control signers,
      showed marked disturbances in the temporal organization and coordination of what
      we argue are the two subsystems of the ASL sign stream--handshape and movement.
      The findings demonstrate a phonetic deficit in Parkinsonian signers, in contrast
      with aphasic signers who showed a disruption in the underlying representation and
      syllabification processes in the language.

PMID- 7712150
TI  - Microvillar cells of the olfactory epithelium: morphology and regeneration
      following exposure to toxic compounds.
AB  - In recent years microvillar cells (MVC) have been identified in the olfactory
      epithelium of numerous species, including rodents, canines, and primates.
      However, there is no consensus on the morphologic or histochemical features of
      this cell, nor is the function of these cells currently known. Previous studies
      have examined MVC during development and in the mature olfactory epithelium, but
      not after toxic insult. A microvillar cell, defined by specific morphologic
      criteria, was studied in adult male Long-Evans rats exposed via inhalation to
      either 200 ppm methyl bromide for 4 h/day, 4 days/week for 2 weeks, or to 635
      micrograms/m3 nickel for 6 h/day for 16 consecutive days, and sacrificed serially
      over several months. The pattern of recovery for MVC differed according to the
      severity and specificity of the insult to the olfactory epithelium. With methyl
      bromide, all cell types were completely depleted from olfactory epithelium
      immediately after injury, including MVC. MVC were slow to repopulate the
      epithelium, and appeared only when olfactory epithelium was complete in other
      respects. With nickel exposure, where the major effect was a gradual decrease in
      sustentacular cells with a thinning of the apical cytoplasm thickness, MVC showed
      a decline during exposure, but reappeared during recovery. In both cases, there
      was no difference in olfactory function, even when MVC were absent from the
      olfactory epithelium. A mature olfactory epithelium appears to be necessary to
      support the presence of this MVC, suggesting that it is not crucial to the
      regeneration processes or recovery of olfactory function, but perhaps plays some
      role, as yet undefined, in the unperturbed olfactory epithelium.

PMID- 7712151
TI  - A role for CNS alpha-2 adrenergic receptors in opiate-induced muscle rigidity in
      the rat.
AB  - A number of potential neurochemical mediators of opiate-induced muscle rigidity
      have been proposed based on the results of systemic drug studies and on knowledge
      of the brain sites implicated in opiate rigidity. The effects of i.c.v.
      pretreatment with selected opioidergic, alpha adrenergic and serotonergic drugs
      on muscle rigidity induced with systemic injection of the potent opiate agonist
      alfentanil (ALF) were investigated in spontaneously ventilating rats. The opiate
      antagonist methylnaloxonium (MN; 0.2-14 nmol), alpha-2 adrenergic agonists
      dexmedetomidine (DEX; 0.4-42 nmol) or 2-(2,6-diethylphenylamino)-2-imidazoline
      hydrochloride (ST91; 4-400 nmol), alpha-1 adrenergic antagonist prazosin (PRZ; 7
      70 nmol) or serotonergic antagonist ketanserin (KET; 18-550 nmol) were injected
      i.c.v. (10 microliters) and ALF (500 micrograms/kg s.c.) was administered 10 min
      later. S.c. electrodes were used to record gastrocnemius electromyographic
      activity. Both MN and DEX dose-dependently and potently antagonized ALF-induced
      rigidity. ST91 produced shorter-lived, less profound, antagonism of ALF rigidity.
      PRZ, at the highest dose tested, produced a delayed and modest reduction in ALF
      rigidity. A large, non-selective, dose of KET incompletely attenuated ALF
      rigidity. These results lend support to the hypothesis that central opioid and
      alpha-2 adrenergic receptors mediate opiate-induced muscle rigidity in the rat.

PMID- 7712152
TI  - Properties of clock-controlled and constitutive N-acetyltransferases from chick
      pineal cells.
AB  - The pineal gland synthesizes its hormone melatonin (O-methyl-N-acetylserotonin)
      from serotonin. Acetyl-CoA: serotonin N-acetyltransferase (SNAT), the enzyme that
      catalyzes the committed step in this biosynthesis, is largely restricted to the
      pineal gland and is regulated by adrenergic and circadian mechanisms. Another
      enzyme, acetyl-CoA: arylamine N-acetyltransferase (ANAT), having an apparently
      similar activity, is also present in the pineal. This enzyme, however, is not
      rhythmically regulated. SNAT activity of cultured chick pineal cells was obtained
      without ANAT after ammonium sulfate precipitation. ANAT activity was retained
      without SNAT activity after pre-incubation at 37 degrees C. Thus, each enzyme
      could be examined independently. Overlap in substrate specificity between the two
      enzymes was minimal. Kinetic analysis of the separated enzyme activities revealed
      that while SNAT operates via a random or ordered bi bi mechanism, ANAT catalysis
      occurs through a ping pong bi bi mechanism with substrate inhibition by acetyl
      CoA. By size-exclusion chromatography, ANAT was confirmed to be 30-35 kDa, and
      SNAT was estimated at 15-20 kDa. Taken together, these results indicate that the
      two enzymes differ in their structure, reactivity, stability, and mechanism of
      catalysis.

PMID- 7712153
TI  - YM796, a novel muscarinic agonist, improves the impairment of learning behavior
      in a rat model of chronic focal cerebral ischemia.
AB  - We studied effects of YM796, a novel muscarinic agonist, on behavioral,
      histological and regional cerebral blood flow changes in the chronic phase after
      focal cerebral ischemia in rats. YM796 (0.03, 0.1, 0.3 and 1 mg/kg) was
      administered orally once a day from the 7th to the 13th day after the permanent
      occlusion of left middle cerebral artery. On the 7th day, rats were trained in
      one-trial step-through passive avoidance task 45 min after drug administration.
      Test trials were carried out on the 8th and 14th days. Neurological deficits,
      including hemiplegia and abnormal posture, were observed on the 7th and 14th
      days. After the completion of behavioral studies, the rats were decapitated and
      cerebral infarction was measured. Regional cerebral blood flow was also measured
      by the hydrogen clearance technique 7 days after MCA occlusion. YM796 (0.1-1
      mg/kg) significantly (P < 0.05) attenuated the impairment of learning behavior in
      a dose-dependent manner without affecting spontaneous locomotor activity. The
      ameliorating effect of YM796 (0.3 mg/kg) on the impaired learning behavior was
      significantly (P < 0.05) suppressed by intracerebroventricular injection of
      pirenzepine (10 micrograms/rat), an M1 antagonist. No significant difference in
      either neurological deficits or cerebral infarction was found between the vehicle
      and YM796-treated groups. Further, YM796 (0.3 mg/kg) had little effect on the
      reduced blood flow in the ipsilateral frontal cortex 7 days after occlusion.
      These results suggest that YM796 improves the impaired learning behavior probably
      by activating central M1 receptors in a rat model of chronic focal cerebral
      ischemia.

PMID- 7712154
TI  - Fos expression within regions of the preoptic area, hypothalamus and brainstem
      during pregnancy and parturition.
AB  - Vaginocervical stimulation, that occurs during mating or with the birth of pups,
      is believed to induce specific sexual and maternal behaviours in the rat as well
      as stimulating a number of neuroendocrine responses including the secretion of
      oxytocin, prolactin and luteinizing hormone. Since the medial preoptic area has
      been implicated in the induction of maternal behaviour, the expression of the
      immediate-early gene product Fos was compared between non-pregnant, late pregnant
      and parturient rats. Although no difference was detected in the number of Fos
      positive neuronal profiles in the preoptic area of non-pregnant and late-pregnant
      rats, a large increase was observed in the medial preoptic nucleus and the
      anteroventral periventricular region, as well as in the hypothalamic supraoptic
      nucleus, of parturient rats. Double labelling for Fos and tyrosine hydroxylase
      immunoreactivity in the brainstem of parturient rats showed the activation of
      catecholaminergic neurons in both the nucleus of the tractus solitarius and in
      the ventrolateral medulla that may form part of the afferent pathway from the
      uterus and cervix to the preoptic area and hypothalamus.

PMID- 7712155
TI  - Fate of lysosomes transported to the dendrites by a colchicine-induced mechanism.
AB  - Lysosomes in hypoglossal motoneurons were retrogradely labeled with fluorescent
      latex microspheres and their distribution as well as that of acid phosphatase was
      examined after a single 50 microgram intracerebroventricular (i.c.v.) injection
      of colchicine. In saline injected controls the fluorescent label was distributed
      mainly in cell bodies. Twenty-four hours after the colchicine injection we
      observed a re-distribution of fluorescent label from the cell body of neurons to
      the dendrites. Seventy-two hours after the colchicine injection the fluorescent
      label had returned from the dendrites to the cell body. A similar pattern was
      obtained by following the effect of colchicine on the distribution of acid
      phosphatase reaction product. We conclude that the reappearance of fluorescent
      label in cell bodies following colchicine treatment is the result of the
      retrograde transport of dendritic lysosomes.

PMID- 7712156
TI  - Cardiovascular effects of 5HT2 and 5HT3 receptor stimulation in the nucleus
      tractus solitarius of spontaneously hypertensive rats.
AB  - The effects of local application of 5-HT2- and 5-HT3-receptor agonists in the
      nucleus tractus solitarius (NTS) on the cardiovascular parameters were
      investigated in anaesthetized spontaneously hypertensive (SH) rats and their
      genetically normotensive precursors (WKY). Unilateral microinjection of picomolar
      doses of a 5HT2 receptor agonist, 2,5-dimethoxy-3-bromo-amphetamine (DOB, 0.025
      0.5 pmol), produced a dose-dependent hypotension and bradycardia in both SH and
      WKY rats. These effects could be prevented by prior local microinjection of a 5
      HT2 receptor antagonist, ketanserin (10 pmol). However, for both cardiovascular
      parameters, DOB was more potent in SH than in WKY rats. Thus, the dose-related
      responses to DOB were shifted to the left in SH as compared to WKY rats.
      Bilateral microinjection of the 5-HT3 receptor agonist, phenylbiguanide (1.7-5
      nmol), produced an increase in blood pressure and reduced the cardiovagal
      component of the baroreflex. These effects were not significantly different in SH
      and WKY rats. These data suggest that 5-HT2 receptors, but not 5-HT3 receptors,
      are supersensitive in the NTS of SH rats.

PMID- 7712157
TI  - Denervation induced abnormal phosphorylation in hippocampal neurons.
AB  - This study demonstrates that combined dopaminergic and cholinergic denervation of
      the hippocampus results in the appearance of morphologically altered, Tau
      reactive, apical dendrites of granule cells in the rat dentate gyrus. The
      denervated granule cells and their apical dendrites also display immunoreactivity
      to a mitogen-activated protein kinase, ERK-1, and also evidence of abnormal
      phosphorylation of these dendrites as revealed by SMI-31 immunoreactivity.
      Dopaminergic denervation alone also causes mitogen activated protein kinase
      reactivity without the Tau-reactive apical dendrities. These results suggest an
      analogy to synaptophysin loss and the appearance of dendritic threads described
      in Alzheimer's disease (AD), as an early stage in the formation of
      neurofibrillary tangles (NFT). This is the first animal model in which abnormal
      phosphorylation of Tau has been shown to be produced experimentally in vivo.

PMID- 7712158
TI  - The functional role of metabotropic glutamate receptors in epileptiform activity
      induced by 4-aminopyridine in the rat amygdala slice.
AB  - The metabotropic glutamate receptor (mGluR) antagonist, (RS)-alpha-methyl-4
      carboxyphenylglycine (MCPG; 500 microM), was tested on intracellularly recorded
      epileptiform activity induced by 4-aminopyridine (4-AP) in amygdala neurons.
      Superfusing 4-AP (1 mM) produced interictal spiking followed by ictal bursting.
      MCPG prevented the progressive transition from interictal spiking to ictal
      bursting but affected neither induction of interictal spiking nor maintenance of
      ongoing ictal bursting. These data suggest that mGluRs may be involved in the
      induction of ictal seizure events.

PMID- 7712159
TI  - Exogenous L-5-hydroxytryptophan is decarboxylated in neurons of the substantia
      nigra pars compacta and locus coeruleus of the rat.
AB  - The aim of the present study is to examine by immunohistochemistry whether
      exogenous L-5-hydroxytryptophan (L-5HTP) is decarboxylated in neurons of the
      substantia nigra pars compacta (SNC) and locus coeruleus (LC) of the rat. In
      normal rats, neurons of the SNC and LC stained intensely for aromatic L-amino
      acid decarboxylase (AADC). No serotonin (5HT)-positive cells were found in the
      two regions of the normal rats. In rats that were intraperitoneally injected with
      L-5HTP alone, the SNC neurons stained deeply for 5HT, but the LC neurons showed
      only a faint staining for 5HT. In rats that intraperitoneally received both a
      monoamine oxidase (MAO) inhibitor and L-5HTP, when compared with the L-5HTP
      injected rats, the LC neurons became much darker in 5HT staining, but the SNC
      neurons showed only a slight increase in 5HT staining. The present findings
      suggest that (i) AADC in dopaminergic neurons of the SNC and in noradrenergic
      neurons of the LC can catalyze the in vivo decarboxylation of exogenous L-5HTP to
      produce 5HT, and (ii) most of the newly produced 5HT in the LC neurons is rapidly
      degraded by endogenous MAO.

PMID- 7712160
TI  - Effect of neuropeptide-Y on tectal field potentials in the toad.
AB  - Field potentials (FP) recorded from the surface of toad's optic tectum (OT) to
      electrical stimulation of the contralateral optic nerve (ON) show initial
      positive deflections P*, followed by negative wave N and positive wave P; the
      former result from axonal inputs, the latter two resemble excitatory and
      inhibitory postsynaptic processes, respectively. Electrostimulation of the
      pretectum ipsilaterally to the recorded OT--preceeding ON-stimulation--strongly
      attenuates the N wave, suggesting pretectotectal inhibitory influences. The N
      wave of the tectal FP evoked by ON-stimulation is reduced, too, after application
      of the neuropeptide-Y (NPY) to the tectal surface. Previous authors have shown
      that frog's pretectum contains NPY immunoreactive pretectotectal projecting
      cells.

PMID- 7712161
TI  - Cerebrospinal dopamine metabolites in rats after intrastriatal administration of
      6-hydroxydopamine or 1-methyl-4-phenylpyridinium ion.
AB  - Dopamine (DA) and its main cerebral metabolites, dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA) were measured in striatum and cerebrospinal
      fluid (CSF) from cisterna magna in rats bilaterally lesioned by intrastriatal
      administration of 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium ion
      (MPP+). 6-OHDA caused a progressive lesion in striatum that is only moderately
      reflected in the decrease in dopamine metabolite concentration in CSF. MPP+
      caused an acute but less selective lesion in the dopamine striatal system, as
      indicated by a significant reduction in striatal GABA content, followed by a slow
      recovery in dopamine striatal metabolism and content. The locomotor activity was
      dramatically reduced in both groups 48 hours after the treatment but remained
      significantly decreased after two months only in 6-OHDA lesioned animals. A
      positive correlation was found between HVA CSF concentration and striatal DA
      content in MPP+ lesioned rats, but not in 6-OHDA lesioned rats. It is concluded
      that the concentration of dopamine metabolites in CSF can be altered only after a
      severe striatal lesion: reduction of striatal dopamine content below 50% of
      normal values and involvement of neuronal or non-neuronal elements other than the
      dopaminergic system, similarly to the lesions caused by MPP+. These results may
      partly explain why CSF dopamine metabolites concentrations were significantly
      decreased both in advanced stages of parkinsonism and in other neurodegenerative
      disorders.

PMID- 7712162
TI  - Effect of nitroprusside on regional cerebral cyclic GMP, blood flow and O2
      consumption in rat.
AB  - This investigation was conducted to test whether topical nitroprusside (NP), a
      cytosolic guanylate cyclase activator, would increase the level of cyclic GMP and
      alter O2 consumption or blood flow in the cerebral cortex of rats. Male Long
      Evans rats were used in a control (n = 9), low dose NP (n = 13, 10(-3) M) or high
      dose NP (n = 12, 10(-2) M) group. Nitroprusside or saline was topically applied
      to the right side of the cerebral cortex and the left side was used as a control.
      The cyclic GMP level was determined in five rats in each group using a
      radioimmunoassay. In the other rats in each group, regional cerebral blood flow
      was measured by [14C]iodoantipyrine and regional arterial and venous O2
      saturations were determined microspectrophotometrically. Nitroprusside
      significantly increased the cyclic GMP level from 21.4 +/- 12.0 pmol/g
      (contralateral cortex) to 52.2 +/- 36.7 pmol/g (NP treated cortex) in low dose
      nitroprusside group and from 19.9 +/- 22.6 pmol/g (contralateral cortex) to 58.5
      +/- 15.1 pmol/g (NP treated cortex) in high dose nitroprusside group. High dose
      nitroprusside significantly increased cerebral blood flow from 80 +/- 11 ml.min
      1.100 g (contralateral cortex) to 114 +/- 11 ml.min-1.100 g (NP treated cortex).
      However, there was no significant difference in O2 extraction and O2 consumption
      between the NP treated cortex and contralateral cortex in either the low or the
      high dose NP groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712163
TI  - Involvement of the PVN and BST in 1K1C hypertension in the rat.
AB  - The paraventricular nucleus of the hypothalamus (PVN) and the bed nucleus of the
      stria terminalis (BST) are two sources of central nervous system (CNS)-derived
      arginine vasopressin (AVP), a nonapeptide that has been implicated in central
      autonomic regulation and in particular in cardiovascular regulation, through its
      actions within the CNS. These experiments were designed to determine if either
      the PVN or the BST were involved in the development of Goldblatt one-kidney one
      clip (1K1C) hypertension in the rat. In order to test this hypothesis, ibotenic
      acid lesions of the PVN or electrolytic lesions of the BST were undertaken in
      both normotensive (sham-operated) rats and in 1K1C rats. In both cases the
      development of 1K1C hypertension was inhibited over the 18-21 days following
      surgery. Lesions of the PVN did not alter normal blood pressure regulation in the
      sham-operated animals, whereas lesions to the BST did affect normal blood
      pressure regulation, resulting in a dramatic increase in blood pressure during
      the initial days following surgery. These studies suggest that the PVN and BST
      are involved in the development of 1K1C hypertension in the rat, moreover the BST
      may also play a role in central cardiovascular control.

PMID- 7712164
TI  - Alterations in dendritic morphology of frontal cortical neurons after basal
      forebrain lesions in adult and aged rats.
AB  - The nucleus basalis magnocellularis (NBM) is the major cholinergic projection to
      neocortex in the rat and plays a role in the modulation of cortical activity.
      Lesions of the NBM decrease thickness of lamina II-III of frontal cortex and
      decrease soma size of lamina II-III neurons. Additionally, aging produces changes
      in neuron size and numbers in the basal forebrain and frontal cortex of rats. We
      assessed dendritic changes in neurons from lamina II-III of frontal cortex in
      adult, middle-aged, and aged rats three months after unilateral lesions of the
      NBM. While lesions did not affect dendritic morphology in young adult rats, they
      decreased total dendritic length in middle-aged and aged rats, with dendritic
      alterations most pronounced in middle-aged rats. In middle-aged rats, lesion
      induced changes in basilar arbor were apparently due to decreased dendritic
      branching: lesions markedly decreased the number of first-, second-, and third
      order branches, but did not affect higher-order branching. In aged rats, lesions
      resulted in a small decrease in dendritic material proximal to the soma and a
      pronounced decrease in dendritic material distal to the soma, apparently due to a
      decrease in the length of terminal branches. These results suggest that the
      plasticity of neocortical neurons in the basalocortical system changes with age,
      and that early in aging this system may be particularly vulnerable to neural
      damage.

PMID- 7712165
TI  - Effect of subthalamic nucleus lesion on mitochondrial enzyme activity in rat
      basal ganglia.
AB  - The subthalamic nucleus (STN) plays a major role in the control of basal ganglia
      output, and its overactivity may be central to the symptoms of Parkinson's
      disease. In order to elucidate the functional relationship between STN and its
      projection nuclei, we studied the short-term (1 week) effect of a selective
      lesion of STN on the activity of succinate dehydrogenase (SDH) and cytochrome
      oxidase (CO), two markers of neuronal activity, in the basal ganglia of rats. STN
      ablation induced a discrete reduction of oxidative metabolism, ipsilaterally to
      the lesion, in substantia nigra pars reticulata and globus pallidus, the rodent
      homologue of lateral globus pallidus. Such changes, ascribable to the
      interruption of the STN excitatory output to these nuclei, were present after 24
      h and remained stable, or increased, throughout the observation period. A
      transitory, ipsilateral decrease was also observed in the caudate-putamen and the
      somato-sensory cortex, likely due to involvement of polysynaptic pathways. SDH
      and CO activity were always altered in the same areas, but SDH changes were more
      pronounced and occurred more rapidly. These results shed further light on the
      role played by STN in the control of basal ganglia output.

PMID- 7712166
TI  - The significance of extracellular GABA in the substantia nigra of the rat during
      seizures and anticonvulsant treatments.
AB  - The effects of the anti-epileptic drugs valproic acid and gamma-vinyl-GABA
      (vigabatrin) on the extracellular content of GABA was determined by
      microdialysis. Probes were implanted in the substantia nigra reticulata (SNR) of
      rats. It was found that gamma-vinyl-GABA (1000 mg/kg) induced a 4-6-fold increase
      in the extracellular content of GABA. This increase lasted for at least 72 h. PTZ
      induced convulsions were partly antagonized by the GVG treatment. The increase of
      extracellular GABA after gamma-vinyl-GABA was not affected by infusion of
      tetrodotoxin. In contrast valproic acid (200 mg/kg), although effective in
      preventing pentylenetetrazol (PTZ)-induced convulsions, did not affect
      extracellular GABA in the SNR. PTZ-induced convulsions did not modify
      extracellular GABA, neither in control rats nor in valproic acid or gamma-vinyl
      GABA pretreated animals. The results do not support the idea that extracellular
      GABA in the SNR plays a significant role in anti-convulsive treatment. However,
      the present data can also be interpreted that extracellular GABA, as sampled by
      microdialysis, is not a reliable marker for GABA release.

PMID- 7712167
TI  - Bradykinin-induced water intake and brain fos-like immunoreactivity in rats.
AB  - We have previously shown that peripheral injection of bradykinin in combination
      with the kininase II inhibitor, captopril, to rats produces a robust water
      intake. We now extend this observation to another kininase II inhibitor,
      enalapril. Water intake increases with dose of dose of bradykinin, but has an
      inverted U-shaped relationship with dose of kininase II inhibitor. The induced
      water intake is completely blocked by peripheral administration of the bradykinin
      antagonist, Hoe 140, and is partly attenuated by peripheral injection of an
      angiotensin (Ang) II receptor antagonist, losartan. Relative to captopril alone,
      the combination of captopril and bradykinin greatly elevated plasma renin
      activity, but did not reduce blood pressure. We further show that, while either
      bradykinin or enalapril alone induce little or no Fos-like immunoreactivity in
      areas of the brain related to fluid balance, their combination induces staining
      in many cells in the supraoptic and paraventricular magnocellular nuclei, as well
      as along the lamina terminalis. These data suggest that bradykinin may have a
      role in regulation of fluid balance, partly mediated through Ang II.

PMID- 7712168
TI  - Involvement of ryanodine receptors in sphingosylphosphorylcholine-induced calcium
      release from brain microsomes.
AB  - Sphingosylphosphorylcholine (SPC) releases Ca2+ from brain microsomes. SPC
      induced CA2+ release differs from IP3-induced Ca2+ release in that it is more
      extensive in the cerebrum than in the cerebellum. SPC has little effect on [3H]
      IP3 binding but enhances [3H] ryanodine binding, as expected for an activator of
      ryanodine receptors. SPC-induced Ca2+ release is inhibited by ryanodine receptor
      blockers but not by selective blockers of IP3 receptors. We conclude that SPC
      releases Ca2+ from brain microsomes by activating ryanodine receptors rather than
      IP3 receptors. Activation of an additional SPC-sensitive pathway for releasing
      Ca2+ is not precluded.

PMID- 7712169
TI  - Reflex changes in the masticatory muscles with load perturbations during chewing
      hard and soft food.
AB  - Reflex changes in masticatory muscles were investigated in naturally behaving
      rabbits while chewing soft food (bread) and hard food (raw rice). To study
      peripheral control mechanisms of mastication, reflex changes in masticatory
      muscles were correlated with the jaw movement trajectories. When the hard food
      was tested, the closing muscle was activated isometrically and the antagonist
      activity was evident during closure. Under such conditions, the so-called
      masseteric inhibitory periods (MIPs) and digastric short bursts (DSBs) were found
      in the closing phase, which was not the case with soft food. The reflex changes
      in the masticatory muscles were similar to those in an unloading reflex or in a
      reflex after tooth tap. Precise comparison of the EMG and the movement orbit
      showed that DSB with MIP was preceded by a trough in the closing velocity which
      bottomed at 8 +/- 1 ms (mean +/- S.D.: n = 9) before the DSB onset. These results
      suggest that the DSB with MIP may be a reflex change generated by periodontal
      mechanoreceptor stimulation after the upper and lower teeth come together with
      hard food, which have a role in regulatory mechanisms of mastication when the
      teeth are suddenly loaded by hard food.

PMID- 7712170
TI  - Responses of neurons in ventrolateral orbital cortex to noxious visceral
      stimulation in the rat.
AB  - In pentobarbital-anesthetized rats, responses of single neurons in ventrolateral
      orbital cortex (VLO) to noxious visceral (colorectal distension, CRD) and
      cutaneous stimulation were recorded. Of 71 neurons identified on the basis of
      spontaneous activity, 44 responded to CRD. CRD caused inhibition of neuronal
      activity in 38, facilitation of activity in four and 'mixed' responses in two of
      these cells. Cutaneous receptive fields were identified in 31 CRD-responsive and
      10 CRD-non-responsive neurons. Cutaneous receptive fields were large and
      bilateral. 25 CRD-responsive cells responded only to noxious cutaneous
      stimulation, six had wide dynamic range responses. Six CRD-non-responsive cells
      responded only to noxious stimuli, four had wide dynamic range responses. No VLO
      neuron responded only to innocuous stimuli. These data are consistent with
      involvement of VLO in visceral nociception, possibly in non-discriminative
      aspects of nociception.

PMID- 7712171
TI  - Targeted disruption of the neurotrophin-3 gene with lacZ induces loss of trkC
      positive neurons in sensory ganglia but not in spinal cords.
AB  - We have replaced the NT-3 gene with Escherichia coli-derived lacZ gene by means
      of homologous recombination in embryonic stem cells and thus produced null mutant
      mice. Mice homozygous for this mutation developed to birth, but most of them
      could not suck well and died within 2 days after birth. The surviving homozygous
      mutant mice displayed movement disorder similar to ataxia. The expression of lacZ
      was widely distributed in the target tissues of peripheral nerves, spinal motor
      neurons, lumbar dorsal root ganglia and trigeminal ganglia during the prenatal
      periods. A neuroanatomical examination revealed that there was marked cell
      reduction present in trigeminal and lumbar dorsal root ganglia in the developing
      homozygous mutant mice. In these tissues, the expression of trkC, a high-affinity
      receptor for NT-3, was markedly reduced. In contrast, we did not find any
      morphological abnormalities, significant cell loss or decreased levels of trkC
      expression in the motor neurons present in the ventral horn of the spinal cord.
      These results indicate that the absence of the NT-3 gene leads to a defect in the
      sensory nervous system, but it may be complemented by other neurotrophins in the
      motor nervous system during the development.

PMID- 7712172
TI  - Inhibition of epileptiform activity by serotonin in rat CA1 neurons.
AB  - This investigation was performed to determine the ability of serotonin in
      inhibiting bicuculline-induced epileptiform bursts in brain slices of male
      Sprague-Dawley rats. In all experiments, intracellular recording techniques were
      employed on CA1 neurons of the hippocampus. The neurons were stimulated either
      directly by the recording electrode or indirectly (synaptic stimulation) using a
      bipolar electrode placed on the CA2/CA3 region. Serotonin (20 microM) inhibited
      the directly evoked bursts of action potentials and caused a membrane
      hyperpolarization and decrease in membrane input resistance in untreated CA1
      neurons. In the same experiments, serotonin inhibited the synaptically evoked
      action potential as well. Additionally, serotonin inhibited epileptiform bursts
      induced by single presynaptic stimuli in the presence of bicuculline. Moreover,
      in the concomitant presence of serotonin and bicuculline, there was a decrease in
      the number of spikes in bursts evoked by direct stimulation. Inhibition of
      epileptiform bursts was also achieved with the selective 5-HT1A agonist 8
      hydroxydipropyl-amino-tetralin (8-OH-DPAT). The presence of the 5-HT3 antagonist
      MDL 72222 (30 microM), and the 5-HT2 antagonist ketanserin (3 microM) did not
      influence the ability of serotonin to inhibit epileptiform bursts. In the
      presence of bicuculline, the inhibitory action of serotonin, 8-OH-DPAT or the
      combination of serotonin, MDL 72222 and ketanserin, was accompanied by a membrane
      hyperpolarization and a decrease in membrane input resistance. To ascertain if
      serotonin can be applied on other models of epilepsy, as well, we demonstrate the
      inhibition of epileptiform activity in the kainic acid treated brain slice
      preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712173
TI  - Pregnenolone sulfate potentiation of NMDA-mediated increases in intracellular
      calcium in cultured chick cortical neurons.
AB  - Pregnenolone sulfate (PS) has been reported to selectively augment glutamate
      induced depolarizations mediated by the NMDA subtype of the glutamate receptor.
      The present study examines the ability of this neuroactive steroid to potentiate
      NMDA-mediated increases in intracellular calcium in cultured chick cortical
      neurons using the fluorescent dye Fura2. PS, in the absence of NMDA and glycine,
      significantly elevated intracellular calcium at 250 and 500 microM. This increase
      in free calcium was significantly attenuated at 250 microM PS by the prior
      addition of 50 microM CNQX, 10 microM dizocilpine or 1 microM nimodipine. NMDA
      and glycine, when added to the cells in saturating concentrations of 500 and 50
      microM, respectively, consistently increased intracellular free calcium over
      baseline levels. In the presence of NMDA and glycine, both 50 and 100 microM PS
      produced a further significant rise in intracellular free calcium. The prior
      addition of CNQX, dizocilpine or both compounds together significantly inhibited
      this elevation in free calcium. The application of the endogenous polyamine
      spermine (250 microM) significantly potentiated the response of chick cortical
      neuronal cells to NMDA and glycine. PS, in the presence of NMDA, glycine and
      spermine, produced a further increase in intracellular free calcium at
      concentrations of 50 and 100 microM. The prior application of CNQX, dizocilpine
      or both compounds together significantly attenuated this rise in free calcium.
      These data confirm that PS is a positive allosteric modulator of the NMDA
      receptor and provide evidence that this neurosteroid does not interact with the
      polyamine modulatory site.

PMID- 7712174
TI  - Early immunohistochemical changes of microtubule based motor proteins in gerbil
      hippocampus after transient ischemia.
AB  - Changes of immunoreactivities for microtubule based motor proteins, kinesin and
      cytoplasmic dynein, and non-motor protein, microtubule associated protein (MAP) 2
      were investigated in gerbil hippocampus after transient ischemia. The
      immunoreactivities for kinesin showed a progressive decrease in hippocampal CA1
      cells from 8 h after transient 5 or 15 min of ischemia that is lethal to the CA1
      cells, while it showed no change after 2 min of ischemia that is non-lethal to
      the cells. The immunoreactivities for cytoplasmic dynein showed a decrease from 3
      or 1 h of reperfusion in the CA1 cells after 5 or 15 min of ischemia,
      respectively. In contrast, the immunoreactivity for MAP2 remained normal until 2
      days in the CA1 cells after 5 min of ischemia. These results showed an early
      changes of microtubule based motor proteins, such as kinesin and cytoplasmic
      dynein in vulnerable CA1 neurons. These changes may affect the mitochondrial
      shuttle system between neuronal cell body and the peripheries such as axon
      terminal and dendrites. This early disturbance may cause a failure to obtain
      newly synthesized nuclear encoded mitochondrial protein, and result in
      mitochondrial dysfunctions and the subsequent cell death.

PMID- 7712175
TI  - Oxytocin and vasopressin release in the olfactory bulb of parturient ewes:
      changes with maternal experience and effects on acetylcholine, gamma-aminobutyric
      acid, glutamate and noradrenaline release.
AB  - Maternal behaviour and the ewe's ability to recognize her lamb depend on
      olfactory cues and parturition, and are facilitated by maternal experience.
      Parturition induces a variety of neurochemical changes in the brain and, in
      particular, oxytocin (OT) release. This peptide injected centrally induces
      maternal behaviour. Oxytocin release occurs in the olfactory bulb (OB) at
      parturition and yet this structure is involved in the process of selective
      bonding with lamb. The present study therefore investigated the possibility that
      oxytocin release in the OB might modulate the release of classical transmitters
      that are known to be important in controlling selective recognition and whether
      maternal experience has any effect on this. We have first used in vivo
      microdialysis to measure OT release, as well as that of the related peptide,
      arginine-vasopressin (AVP), in the OB of maternally experienced and inexperienced
      ewes during parturition. While OT release significantly increased in both
      primiparous and multiparous ewes at parturition this increase was significantly
      greater in multiparous ewes. No significant change of AVP release was observed in
      either group. However, vagino-cervical stimulation (VCS) performed at 6 h post
      partum caused similar increases in OT but not AVP release in both primiparous and
      multiparous ewes suggesting that the first birth experience potentiates the
      ability of VCS to evoke OT release within 6 h of parturition. Using
      retrodialysis, either OT (10 microM) or AVP (10 microM) were infused into the OB
      of multiparous and nulliparous ewes and their effects on modulating acetylcholine
      (ACh), noradrenaline (NA), glutamate and gamma-aminobutyric acid (GABA) release
      were monitored. Both peptides produced an increase of ACh and NA in multiparous
      animals and this effect was either absent or less pronounced in nulliparous
      animals. OT, but not AVP, also increased GABA release equivalently in nulliparous
      and multiparous animals. Glutamate release was not altered in response to OT or
      AVP infusion. These results suggest that OT release in the OB at parturition may
      facilitate the recognition of lamb odours by modulating NA, ACh and GABA release
      which are of primary importance for olfactory memory. The reduced release of OT
      in the OB of primiparous ewes at parturition, together with its reduced ability
      to modulate NA and ACh release, might also partly explain why maternally
      inexperienced animals require a longer period to selectively bond with their
      lambs.

PMID- 7712176
TI  - A serotonin neurotoxin attenuates the phase-shifting effects of triazolam on the
      circadian clock in hamsters.
AB  - Several lines of evidence suggest the potential involvement of serotonergic
      pathways in mediating the effects of activity-inducing stimuli on the circadian
      clock in rodents. The aim of the present 3 experiments was to examine the effects
      of the serotonergic neurotoxin, p-chloroamphetamine (PCA, 10 mg/kg) on: (1) the
      monoamine levels of the hypothalamus, frontal cortex and hippocampus in the
      hamster; (2) the phase shifts in the circadian rhythm of locomotor activity of
      hamsters in response to treatment with the short-acting benzodiazepine, triazolam
      (7.5 mg/kg); and (3) the magnitude of the acute increase in locomotor activity
      associated with triazolam administration in this species. The administration of
      PCA to hamsters caused changes of specific monoaminergic systems in the
      hypothalamus, that were limited to a selective decrease in serotonin levels 7
      days post-treatment. The phase shifts of the circadian clock in response to
      triazolam treatment at CT 6 were considerably attenuated following the
      administration of the 5-HT neurotoxin. The total amount and the profiles of
      triazolam-induced wheel-running and general cage activity between CT 6 and CT 12
      were not significantly affected by the PCA treatment. The finding that a 5-HT
      neurotoxin can attenuate the phase-shifting effects of triazolam in hamsters,
      without interfering with its activity-inducing properties, suggests that
      serotonergic afferents might be involved in the mechanism for non-photic phase
      shifting of the circadian system.

PMID- 7712177
TI  - Characterization of the association of phospholipase C-delta with Alzheimer
      neurofibrillary tangles.
AB  - Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal
      transduction. We have previously demonstrated that an antibody to the PLC
      isozyme, PLC-delta, intensely stained neurofibrillary tangles (NFT) in the brain
      tissue of AD patients [Am. J. Pathol., 139 (1991) 737-742]. To clarify the
      crucial involvement of abnormal PLC-delta accumulation contributing to the
      formation of NFT, we performed light and electron microscopic
      immunocytochemistry. To determine PLC-delta's association with NFT, its
      resistance to solubilization was also studied. Anti-PLC-delta antibody marked the
      same NFT-bearing neurons containing tau immunoreactivity with tau more clearly on
      NFT filaments and PLC-delta covering it superficially at the light microscope
      level. The double stained preparations with anti-PLC-delta antibody and bFGF
      binding suggested that PLC-delta is an intracellular marker and is not retained
      after neuronal death. Employing immunoperoxidase and immunogold electron
      microscopic immunocytochemistry, we found that the antibody to PLC-delta reacts
      mostly with amorphous granular materials, and occasionally with some abnormal
      filaments within NFT. Nevertheless, PLC-delta in NFT was resistant to removal by
      high salt or ionic detergent, indicating it is an integral NFT component. These
      results indicate that antigenic determinants unique to PLC-delta are mainly
      present intraneuronally on the amorphous granular components of NFT as well as
      the abnormal filaments, suggesting PLC-delta's interactions and possible role in
      the formation of intraneuronal filamentous inclusions in AD.

PMID- 7712178
TI  - Dietary alpha-linolenate/linoleate balance influences learning and memory in the
      senescence-accelerated mouse (SAM).
AB  - The senescence-accelerated mouse (SAMP8) is a model of age-related deterioration
      of memory and learning ability. A semipurified diet supplemented either with
      safflower oil (rich in linoleate) or with perilla oil (rich in alpha-linolenate)
      was fed to SAMP8 mouse dams and their pups. The offspring (males from several
      mothers) at 28 weeks of age were used for behavioral tests. The proportions of n
      3 and n-6 highly unsaturated fatty acids in brain phospholipids reflected the n
      3/n-6 balance of the diets. The learning and memory abilities of the two dietary
      groups were tested with the Sidman active avoidance task and the light and dark
      discrimination learning test. The group given perilla oil showed much greater
      improvement in learning in the Sidman active avoidance task than did the group
      fed safflower oil. In the light and dark discrimination learning test, the total
      number of responses to positive and negative stimuli was lower in those fed
      perilla oil, and their responses to positive stimuli were higher than to negative
      stimuli after the 10th session. Consequently, the correct response ratios of
      discrimination were higher in the perilla oil group than in the safflower oil
      group. In the open field test, the total amount of locomotor activity during 5
      min was lower in the perilla oil group at 7 months of age than in the group fed
      safflower oil.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712179
TI  - Relation of [Ca2+]i to dopamine release in striatal synaptosomes: role of Ca2+
      channels.
AB  - We compared the effects of KCl and 4-aminopyridine (4-AP) stimulation on the
      coupling of Ca2+ channel activation to [3H]dopamine ([3H]DA) release in rat
      striatal synaptosomes and used specific Ca2+ channel blockers to discriminate
      between the different VSCC's activated by the two stimulatory agents. We found
      that whereas [3H]DA release is strictly Ca(2+)-dependent in the case of KCl
      depolarization, 4-AP, at concentrations above 100 microM, progressively causes a
      large Ca(2+)-independent release of [3H]DA. Thus, at 1 to 3 mM 4-AP, as much as
      80-95% of the [3H]DA release is Ca(2+)-independent and can be partially blocked
      by nomifensine, indicating that some [3H]DA release is occurring through reversal
      of the DA carrier. Therefore, in the studies relating [Ca2+]i to [3H]DA release
      we selected 4-AP concentrations lower than 100 microM and corrected for the
      Ca(2+)-independent release. Under these conditions, we determined that: (1) Ca2+
      entry through N-type VSCC's is involved in [3H]DA release both in the case of KCl
      depolarization (35% inhibition by omega-CgTx) and in 4-AP stimulation (23%
      inhibition by omega-CgTx); (2) Ca2+ entering through P-type and/or Q-type VSCC's
      is also involved in [3H]DA release due to 4-AP stimulation (26% inhibition by 200
      nM omega-Aga IVA); (3) Neomycin (0.35 mM) inhibited the [3H]DA release due to 4
      AP stimulation by about 20% and decreased the KCl induced [3H]DA release by 55%;
      the effects of neomycin (0.35 mM) and omega-CgTx were additive in both cases,
      indicating that, at this concentration, the antibiotic does not affect
      significantly N-type Ca2+ channels; (4) When applied together, omega-CgTx and
      omega-Aga IVA inhibited the 4-AP stimulated [3H]DA release by about 40-50%,
      suggesting that the remaining large fraction of the VSCC's activated by 4-AP
      stimulation are non-N, non-P VSCC's and are coupled to Ca(2+)-dependent [3H]DA
      release; (5) The contribution of L-type VSCC's is uncertain, since there seemed
      to be a small contribution in the case of KCl depolarization, but not in the case
      of 4-AP stimulation. On the whole, the results suggest that the release of [3H]DA
      in the rat striatal nerve terminals depends on Ca2+ entry through N-, P-,
      possibly Q-, and other non-N-, non-P-type VSCC's when either KCl or 4-AP
      stimulation is utilized.

PMID- 7712180
TI  - Peripheral hyperalgesia in experimental neuropathy: exacerbation by neuropeptide
      Y.
AB  - Injury of peripheral nerves often results in hyperalgesia (an increased
      sensitivity to painful stimuli). This hyperalgesia is mediated in part by
      sympathetic neurotransmitters. We examined the effect of neuropeptide Y (NPY),
      specific Y1 and Y2 agonists, and an NPY antagonist on peripheral hyperalgesia in
      rats whose sciatic nerves had been partially transected. NPY and the Y2 agonist,
      N-acetyl [Leu28,Leu31] NPY 24-36 exacerbated both mechanical and thermal
      hyperalgesia, while the Y1 agonist, [Leu31, Pro34]NPY relieved thermal
      hyperalgesia. Mechanical and thermal hyperalgesia were both relieved by alpha
      trinositol (PP56), a non-competitive antagonist of the actions of neuropeptide Y.
      Hyperalgesia was also relieved by surgical sympathectomy, which eliminated the
      effects of NPY and its agonists. These results suggest that neuropeptide Y
      contributes to peripheral hyperalgesia by actions at Y2 receptors, which may be
      located on postganglionic sympathetic terminals.

PMID- 7712181
TI  - Androgenic-anabolic steroids modify beta-endorphin immunoreactivity in the rat
      brain.
AB  - Immunocytochemical localization of beta-endorphin in the brains of intact and
      castrated male rats was conducted after the administration of high levels of
      androgenic-anabolic steroids (AAS; 14 daily injections of sesame oil or a
      cocktail of 2 mg/kg testosterone cypionate, 2 mg/kg nandrolone decanoate, and 1
      mg/kg boldenone undecylenate) at doses commonly self-administered by athletes who
      are considered 'heavy abusers'. In normal intact oil-treated males, cytoplasmic
      immunoreactivity was prevalent throughout the arcuate nucleus while intense fiber
      tract immunoreactivity was most prevalent in the bed nucleus of the stria
      terminalis and the paraventricular hypothalamic nucleus. Administration of AAS
      significantly decreased the number of neurons exhibiting cytoplasmic
      immunoreactivity only in the rostral region of the arcuate nucleus. AAS treatment
      had no effect on beta-endorphin immunoreactivity in the middle or caudal aspects
      of the arcuate nucleus.

PMID- 7712182
TI  - Cryopreserved neuronal cells in long-term cultures of dissociated rat cerebral
      cortex: survival and morphometric characteristics as revealed by
      immunocytochemistry.
AB  - Blocks of fresh tissue from embryonic rat cerebral cortex, dissociated either
      prior to or after freezing, were stored for up to 10 months in liquid nitrogen at
      -196 degrees C with 7% dimethylsulfoxide (DMSO) as cryoprotectant. Slow freezing
      and rapid thawing, a reduced medium volume and moderate elevation of both
      extracellular K+ (20 mM) and sera (20%) promoted survival of neurons (up to 7
      weeks) on polylysine-coated glass coverslips. Although there was cell loss
      associated with freezing, the surviving cells developed morphological and
      immunocytochemical properties similar to those expressed by unfrozen cells when
      using anti-GFAP (glial fibrillary acidic protein), anti-NSE (neuron specific
      enolase) and anti-GABA (gamma-aminobutyric acid) antibodies. A comparative
      computer-aided analysis of the morphometric patterns of GABA-IR neurons allowed
      the individualization of two similar populations in both fresh and frozen
      controls. NSE- and GABA-immunoreactive (IR) cells were counted in frozen controls
      and thienyl-phencyclidine (TCP)-treated cultures. The latter yielded fewer cells
      whereas it was the opposite in fresh TCP-treated cultures. In view of these
      findings, a detailed analysis of the effects of both neuroprotective and
      neurotoxic agents on frozen cells is undertaken before considering that
      cryopreservation might be a suitable storage method for clinical trials of neuron
      grafting.

PMID- 7712183
TI  - Colocalization of dopamine and serotonin in the rat pituitary gland and in the
      nuclei innervating it.
AB  - The nerve terminals in the intermediate and posterior lobes of the rat pituitary
      gland are reported to show colocalization of serotonin and tyrosine hydroxylase.
      This study examined the extent of this colocalization in the pituitary gland and
      in the nuclei considered to project to the pituitary. In the intermediate lobe,
      two types of nerve fibers were encountered, one containing serotonin (5-HT-IR)
      and tyrosine hydroxylase (TH-IR) immunoreactivities and the other showing 5-HT-IR
      only. Instead, there was no colocalization in the posterior lobe. In the
      hypothalamus, colchicine treatment with L-tryptophan and pargyline injections
      resulted in 5-HT-IR in some neurons in the dorsomedial, periventricular and
      arcuate nuclei, some of which in the arcuate and periventricular nuclei were also
      TH-IR. In the raphe nuclei no colocalization of 5-HT-IR and TH-IR was observed.
      Catecholamine neurotoxin, 6-hydroxydopamine, abolished the 5-HT-IR and
      dramatically reduced the TH-IR in the intermediate lobe nerve fibers. Both
      effects were prevented by cocaine, a monoamine uptake inhibitor, but not by
      fluoxetine, a specific serotonin uptake inhibitor. Serotonin neurotoxin p
      chloroamphetamine (PCA) had no effect on intermediate lobe fibers, although it
      caused complete disappearance of 5-HT-IR from the posterior lobe nerve fibers.
      This effect was prevented by fluoxetine. Our results indicate, that
      colocalization of serotonin and TH observed in the intermediate lobe occurs both
      in the nerve terminals within the lobe and in some nuclei that innervate it.
      Furthermore, drug treatments suggest that serotonin in the intermediate lobe is
      localized in catecholaminergic fibers, which do not posses a specific serotonin
      uptake mechanism.

PMID- 7712184
TI  - Spatial periodicity of NADPH-diaphorase and synaptophysin, but not SNAP-25,
      reactivity in the monkey cerebellar cortex.
AB  - We recently described a parasagittal patchy organisation of nicotinamide adenine
      dinucleotide phosphate diaphorase (NADPH-d) activity in the granular layer of the
      rat cerebellum. We now report the pattern of NADPH-d distribution in the primate
      cerebellum and its relationship to two synaptic proteins, synaptophysin and
      synaptosomal associated protein 25 kDa (SNAP-25), using histochemistry and
      immunocytochemistry. NADPH-d reactivity was localised in the molecular and
      granular layers (ML, GL) and a subset of infraganglionic plexuses (IGPs), but not
      in the Purkinje cell layer and the white matter. In ML, the histochemical
      reactivity was dense and relatively homogeneous in the neuropil, and moderate in
      the stellate cells. A patchy organisation of NADPH-d in GL was detected in both
      horizontal and parasagittal sections. In the IGPs staining for NADPH-d revealed
      modular positive zones alternating with negative ones. The positive and negative
      IGP zones were usually congruent with the high and low NADPH-d reactivity in GL,
      respectively. Both synaptic proteins were strongly expressed in the neuropil in
      ML and GL, and their patterns were relatively homogeneous. However, synaptophysin
      was present in a subpopulation of IGPs organised in modules which corresponded to
      those expressing NADPH-d. Our results indicate that the NADPH-d modular system is
      more complicated in the primate cerebellum than in the rat. In addition, we have
      provided suggestive evidence of a co-expression of NADPH-d and synaptophysin in
      selected IGP modules in primate cerebellum, which suggests that nitric oxide may
      be involved in the activity of the Purkinje cells by affecting the basket cell
      synaptic input.

PMID- 7712185
TI  - Different rules of spatial summation from beyond the receptive field for spike
      rates and oscillation amplitudes in cat visual cortex.
AB  - We measured spike rates in parallel with visually induced oscillations of multi
      unit activity (MUA) and local field potentials (LFP) from cortical areas 17 and
      18 of anesthetized cats. Variations in the three response types were
      systematically correlated with stimulus size and placement. Oscillation
      amplitudes of both MUA and LFP were on average low with stimuli covering just the
      receptive field and they increased progressively with larger stimuli, whereas
      average spike rates rather decreased monotonically with stimulus sizes beyond the
      receptive field (area 18) or reached a plateau with stimuli in the far surround
      (area 17). Thus, spike rates and oscillation amplitudes follow different rules of
      spatial summation. Since the spatial spread of the synchronized components of
      oscillations roughly matches the horizontal divergence zone of the pyramidal
      cells' axonal collaterals in area 17 and 18, the interconnected system of
      neighbouring columns seems to constitute a functional unit, within which the
      oscillations could exert their functional role.

PMID- 7712186
TI  - Quantification of the serotonin hyperinnervation in adult rat neostriatum after
      neonatal 6-hydroxydopamine lesion of nigral dopamine neurons.
AB  - Light microscope autoradiography after uptake and storage of tritiated serotonin
      (5-HT) in brain slices was used to count 5-HT axon terminals (varicosities) in
      the 5-HT-hyperinnervated neostriatum of adult rats subjected to neonatal 6
      hydroxydopamine treatment and age-matched, normal controls. After correction for
      incomplete autoradiographic exposure and for section thickness, the results were
      expressed in millions of varicosities per mm3 of tissue. Control values ranged
      from 4.8 in the rostral to 6.3 in the caudal neostriatum (5.8 at intermediate
      level), for an average of 5.6. The corresponding values in 5-HT-hyperinnervated
      tissue ranged from 9.7 to 7.7 (8.8 at intermediate level), for an average of 8.7
      and increases of 102%, 52% and 22% above control in the rostral, intermediate and
      caudal neostriatum, respectively (average increase of 55%). These data confirmed
      the predilection of the 5-HT hyperinnervation for the rostral neostriatum and
      demonstrated its presence in the caudal neostriatum also.

PMID- 7712187
TI  - Electrical recordings of magnocellular supraoptic and paraventricular neurons
      displaying both oxytocin- and vasopressin-related activity.
AB  - In suckled rats, some magnocellular neurons displayed both vasopressin-related
      phasic activity and oxytocin-related milk ejection bursts. Characteristics of
      basal activity and interspike intervals resembled those of vasopressin neurons.
      Bursts were coincident with those of oxytocin neurons and were facilitated by
      centrally injected oxytocin, but had lower maximum instantaneous frequency and
      often no after-inhibition. These data provide evidence of magnocellular neurones
      of mixed electrophysiological phenotype and complement reports of peptide
      coexistence.

PMID- 7712188
TI  - Formation of connections between cultured identified neurones from the pleural
      ganglion of the pteropod mollusc Clione limacina.
AB  - A cluster of electrically interconnected neurosecretory cells (the 'white cells')
      involved in the control of reproductive behavior was identified in the right
      pleural ganglion of the marine mollusc, Clione limacina. Pleural ganglia also
      contain large neurons (PL1 and PL2) having no connections with each other and
      with the white cells. Most isolated white cells put into the simple unconditioned
      medium (50% L-15) adhered to the bottom of uncoated dishes and demonstrated
      neurite outgrowth for 7-10 days. If growing processes overlapped, the white cells
      formed electrical connections with each other, but they formed no connections
      with the PL1 and PL2 neurons. It is concluded that in the case which was under
      study cellular intrinsic properties were sufficient for the formation of
      'correct' connections between neurones.

PMID- 7712189
TI  - Glutamate effect on synaptic transmission mediates neurotoxicity in dissociated
      rat hippocampal neurons.
AB  - In dissociated rat hippocampal neurons, slow bath application (1 ml/min) of
      glutamate (50 microM) increased both excitatory and inhibitory synaptic
      activities. This glutamate effect was abolished by tetrodotoxin or cadmium. The
      constant perfusion (1 h) of glutamate 50 microM was toxic to the neurons. This
      toxicity was also blocked by TTX. This suggests that unlike the excitotoxicity at
      a high (mM) concentration, the glutamate toxicity at 50 microM is mediated by its
      effect on synaptic transmission.

PMID- 7712190
TI  - Tau immunoreactivity associated with aluminum maltolate-induced neurofibrillary
      degeneration in rabbits.
AB  - Intracisternal administration of aluminum maltolate to rabbits produces a marked
      argyrophilic neurofibrillary degeneration (NFD) which is also immunoreactive for
      both phosphorylated and non-phosphorylated microtubule associated protein tau.
      Using tissue fixation in PBF, the monoclonal antibodies Tau-2 and AT8 stain the
      NFD. Dephosphorylation markedly reduces the positivity of AT8. Using PLP-fixed
      tissue, monoclonal antibody Tau-1 also immunostains aluminum-induced NFD.

PMID- 7712191
TI  - Acute interactive effects of MK-801 and morphine on cortical EEG and EEG power
      spectra in rats.
AB  - The interaction between MK-801 and morphine-induced effects on cortical
      electroencephalography (EEG) was investigated. Rats were administered one of five
      MK-801 doses (IP) prior to morphine (IV). MK-801 dose-dependently increased
      morphine-induced global spectral power, duration of morphine-induced EEG bursts
      and latency to sleep onset, and decreased morphine-induced mean frequency,
      mobility, complexity, and edge frequency. MK-801 pretreatment shifted the
      relative distribution of total power to the left. Significant interaction effects
      were found for all spectral parameters except peak frequency. A second group of
      rats was administered MK-801 prior to an increasing cumulative morphine dose. MK
      801 increased maximal morphine effects on all spectral parameters except peak
      frequency. The results are in agreement with those of recent analgesia and in
      vitro studies in spinal neurons, and support observations of a synergistic
      interaction between effects of NMDA antagonism and morphine. These data further
      suggest that the component of cortical EEG that is produced by mu-opioid- and
      NMDA-receptor interactive effects may be dominated by an inhibitory effect of
      morphine on NMDA receptor activity.

PMID- 7712192
TI  - Unscheduled brain DNA synthesis, long-term potentiation, and depression at the
      perforant path-granule cell synapse in the rat.
AB  - We investigated the effect of long-term potentiation (LTP) of the perforant path
      granule cell synapse, on the synthesis of DNA in the target area and in
      polysynaptically stimulated hippocampal (CA3/CA1) and cortical areas (entorhinal,
      temporal, and occipital cortices) in the rat. The contralateral nonstimulated
      side was used as a control. The degree of LTP was indexed by the field EPSP and
      population spike amplitude recorded in the dentate area of the stimulated side
      before and after high frequency stimulation (250 Hz, 250 ms) every 30 min. DNA
      synthesis was evaluated in tissue homogenates after a 3-h period of incorporation
      of 3H-thymidine. DNA synthesis was significantly lower in the stimulated side in
      the hippocampal cortex CA3/CA1 (-25%), and in the entorhinal cortex (-50%), but
      not in the dentate area. In addition, the occurrence of preparations without
      expression of LTP allowed the analysis of unscheduled brain DNA synthesis (UBDS)
      in a supposedly long-term depression (LTD) subgroup. UBDS was higher in the group
      without LTP (no-LTP group) than in that with a significant LTP expression (LTP
      group) on both sides of the brain. Furthermore, correlative analyses revealed
      that UBDS covaried with LTP of the EPSP (but not of population spike) in the
      dentate area and in extratarget hippocampal subregions on both sides and in
      dorsal cortex on the stimulated side. Further, regional crosscorrelation analyses
      revealed a high degree of coupling among brain sites following LTP.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7712193
TI  - In vivo effects of (-)-nicotine on ethanol-induced increase in glucose
      utilization in the mouse cerebellum.
AB  - The purpose of this study was to investigate the possible in vivo effects of (-)
      nicotine, ethanol, and an adenosine agonist N6-cyclohexyladenosine (CHA) when
      injected individually as well as in various combinations on glucose utilization
      in the fresh cerebellar slices of mice. Mice received ICV (-)-nicotine or CHA
      followed 5 min later by a test dose of ethanol (2 g/kg; IP). Animals were killed
      20 min postethanol treatment and fresh slices (300 microns) of cerebellum were
      incubated in a glucose medium in Warburg flasks using 14C-glucose as a tracer.
      Trapped 14CO2 was counted to estimate glucose utilization. Ethanol treatment
      markedly accentuated glucose utilization, whereas the pretreatment with (-)
      nicotine (125 and 250 ng, ICV) resulted in a significant attenuation in the
      ethanol-induced increase in glucose utilization. However, ICV (-)-nicotine (125
      ng) alone did not produce any change in the cerebellar glucose utilization. The
      attenuation of ethanol-induced increase in glucose utilization by (-)-nicotine
      was nearly totally blocked by ICV hexamethonium, a purported nicotinic
      antagonist, suggesting participation of cholinergic-nicotinic receptors. The (-)
      nicotine pretreatment also significantly attenuated both the ICV CHA (25 ng)
      induced increase in glucose utilization and the accentuation of ethanol-induced
      increase in glucose utilization by CHA. The antagonistic effect of (-)-nicotine
      on CHA- and ethanol-induced increase in glucose utilization indicating an
      interaction between (-)-nicotine and ethanol and between (-)-nicotine and
      adenosine may suggest involvement of postreceptor (nicotinic and adenosine)
      mechanisms including ionic channels.

PMID- 7712194
TI  - Reciprocal synaptic relations between enkephalinergic and GABAergic neurons in
      the area postrema of the rat.
AB  - A preembedding, double immunostaining technique was used to study synaptic
      relations between enkephalinergic and GABAergic neurons in the area postrema of
      the rat. As a main result, the enkephalinergic dendrites received many synapses
      from GABAergic axon terminals, and most of the synapses were symmetrical.
      Enkephalinergic neuronal perikarya received a few synapses from GABAergic axon
      terminals, and a few enkephalinergic axon terminals were found presynaptic to
      GABAergic neurons. Synapses between enkephalinergic profiles were frequent, but
      no axo-axonic synapses were seen. These findings suggest that GABAergic
      innervation of enkephalinergic neurons is the main relation between the two kinds
      of neurons in the area postrema. The synapses between the enkephalinergic axon
      terminals and GABAergic neurons might be explained as being part of the local
      servo system of the area postrema.

PMID- 7712195
TI  - Blockade of metabotropic glutamate receptors prevents long-term memory
      consolidation.
AB  - Metabotropic glutamate receptor activation has been shown to be essential for
      establishment of long-term potentiation, a phenomenon increasingly thought to be
      associated with the laying down of permanent memory. However, these receptors may
      also play a part in the initiation of protein kinase C activity, which has been
      demonstrated to be involved in prelong-term memory processes. Blockade of the
      metabotropic glutamate receptors by the specific antagonist, (RS)-alpha-Methyl-4
      carboxyphenylglycine (500 microM) is shown to induce amnesia during a long-term
      memory stage in day-old chicks trained on a passive avoidance task, and to have
      no effect on prelong-term stages. The results suggest a specific role for these
      receptors in a possibly LTP associated mechanism of memory processing.

PMID- 7712196
TI  - Activity of neurons in the lateral preoptic area during drinking behavior by the
      rat.
AB  - Rats were trained to drink water, sucrose solution, and saline while their heads
      were painlessly held in a stereotaxic apparatus with an attachment fixed to the
      skull. A total of 286 neurons in the lateral preoptic area (LPO) were recorded
      during the drinking behavior. During water intake, 40% of the neurons tested were
      either excited or inhibited. Sucrose elicited responses in 25% of the neurons,
      and saline in 34%. Of the 52 neurons recorded while rats drank all test
      solutions, 8 specifically responded to water, 3 were sucrose specific, 4 were
      saline specific, 12 responded to all solutions, and the remaining 25 did not
      respond to any solutions. Artificial cerebrospinal fluids (ACSFs) with
      physiologically hypertonic (+30 mOsm/kg, by NaCl or mannitol) and hypotonic (-30
      mOsm/kg) osmotic pressure were applied to 88 neurons through a multibarrel
      micropipette. Of these neurons, 15 (17%) were hypotonic-sensitive; they were
      excited by hypotonic ACSF and/or inhibited by hypertonic ACSFs. There were 4 (5%)
      that were hypertonic-sensitive; they were excited by hypertonic ACSFs and/or
      inhibited by hypotonic ACSF. Of six hypotonic-sensitive neurons examined, three
      were water specific, and none were sucrose nor saline specific. Of four
      hypertonic-sensitive neurons, one was water specific, and another was saline
      specific. These results showed activity of some LPO neurons specifically related
      to water intake. Osmosensitive neurons in the LPO may regulate water intake.

PMID- 7712197
TI  - Osmosensitive hypothalamic neurons and their responses to cardiovascular receptor
      activation.
AB  - Neurons in the rostral hypothalamic areas were examined with physiologically
      hypertonic (+30 mOsm/kg, by NaCl or mannitol) and hypotonic (-30 mOsm/kg)
      artificial cerebrospinal fluids (ACSFs) applied by pressure through a multibarrel
      micropipette in urethane-anesthetized rats. Of 304 neurons tested, 39 were
      excited by the hypertonic ACSFs and/or inhibited by the hypotonic ACSF, and 35
      were inhibited by the hypertonic ACSFs and/or excited by the hypotonic ACSF. The
      former cells were designated hypertonic-sensitive and the latter hypotonic
      sensitive. Both types of osmosensitive neurons were diffusely scattered in the
      examined areas, but neurons in the lateral preoptic area and the bed nucleus of
      the stria terminalis responded more frequently (30-40%) to the osmotic stimuli.
      Osmosensitive and insensitive neurons were recorded during activation of the baro
      and volume receptors of the cardiovascular system. Of seven neurons that were
      excited during temporal hypotension induced by intravenous administration of
      nitroprusside, five were hypertonic-sensitive and two were osmotically
      insensitive. Hypertonic-sensitive neurons may be activated during dehydration,
      which increases the osmotic pressure and decreases the volume of body fluids. Of
      six neurons that were excited during temporal hypertension induced by intravenous
      administration of phenylephrine, four were hypotonic-sensitive and two were
      osmotically insensitive. Hypotonic-sensitive neurons may be activated during
      rehydration or overhydration. Osmosensitive neurons probably integrate
      cardiovascular and osmotic information that is important for the central
      regulation of body fluids.

PMID- 7712198
TI  - Anatomic patterns of Fos immunostaining in rat brain following systemic endotoxin
      administration.
AB  - To identify brain neurons that participate in the acute phase response, rat
      brains were examined immunocytochemically for Fos protein following the
      intravenous administration of bacterial endotoxin (lipopolysaccharide, LPS). Two
      to three hours after the injection of LPS, 150 micrograms/kg body weight, to
      adult male Long-Evans rats, a consistent anatomic pattern of Fos immunostained
      cell nuclei is seen. In the brain stem, prominant Fos immunostaining is induced
      in tyrosine hydroxylase immunoreactive neurons of the caudal ventral-lateral
      medulla (the A1 cell group), in both tyrosine hydroxylase positive and negative
      neurons of nu. tractus solitarius, in the parabrachial nu., and in a few neurons
      of the locus ceruleus. In the hypothalamus, endotoxin induces Fos expression in
      magnocellular neurons of the paraventricular and supraoptic nuclei and
      internuclear cell groups. A higher percentage of oxytocin-immunoreactive cells is
      double labeled for Fos nuclear immunostaining than vasopressin-immunoreactive
      cells. A minority of somatostatin immunoreactive periventricular hypothalamic
      neurons are Fos positive. Other hypothalamic nuclei that contain endotoxin
      induced Fos nuclear immunostaining include the parvocellular neurons of the
      paraventricular nu., the dorsomedial and arcuate nuclei, the lateral
      hypothalamus, the dorsal hypothalamic area (zona incerta), and the median nucleus
      of the preoptic area. LPS induces numerous Fos-positive neurons in regions known
      to respond to a variety of stressful stimuli; these regions include the preoptic
      area, bed nucleus of the stria terminalis, lateral septum, and the central and
      medial nuclei of the amygdala. Moreover, Fos nuclear immunostaining is seen in
      neurons of circumventricular organs: the organum vasculosum of the lamina
      terminalis, the subfornical organ, and the area postrema. The maximum intensity
      of Fos nuclear immunostaining occurs 2-3 h after endotoxin administration and
      declines thereafter. It is attenuated by pretreatment with indomethacin, 25 mg/kg
      body weight Sc, or dexamethasone, 1 mg/kg IP. These observations are consistent
      with the participation of a variety of brain neuronal systems in the acute phase
      response and elucidate the functional neuroanatomy of that response at the
      cellular level.

PMID- 7712199
TI  - Distribution of parvalbumin immunoreactivity in the cat diencephalon.
AB  - The distribution of parvalbumin-immunoreactive cell bodies and fibers in the cat
      diencephalon has been analyzed by using the avidin-biotin immunoperoxidase
      technique. The thalamus showed a higher density of immunoreactive cell bodies
      than the hypothalamus. A high or moderate density of perikarya and a high density
      of fibers containing parvalbumin was observed in the nuclei lateralis posterior,
      lateralis dorsalis, pulvinar, corpus geniculatum laterale, reticularis, medialis
      dorsalis, centrum medianum, subparafascicularis, ventralis postero-medialis,
      ventralis postero-lateralis, habenularis medialis, parafascicularis, corpus
      geniculatum mediale, centralis lateralis, rhomboidens, reuniens, centralis
      medialis, ventralis medialis, ventralis lateralis, parataenialis, anterior
      ventralis, anterior medialis, ventralis anterior, hypothalamus posterior, corpus
      mamillare, area hypothalamica dorsalis, and in the nucleus suprachiasmaticus.
      Moreover, a high or moderate density of immunoreactive fibers and a low density
      of parvalbumin-immunoreactive cell bodies was observed in the nuclei
      periventricularis anterior, anterior dorsalis, habenularis lateralis, corpus
      geniculatum laterale (pars ventralis), periventricularis hypothalami,
      hypothalamus lateralis, hypothalamus anterior, and in the hypothalamus
      dorsomedialis.

PMID- 7712200
TI  - Fos activation in cultured tyrosine hydroxylase and oxytocin immunoreactive
      neurons.
AB  - Fos and other immediate early gene products are used as markers for neuronal
      activity. We identified Fos immunocytochemically after KCI-induced depolarization
      of cultured hypothalamic neurons. Five-day cultures were treated for 1 h with 50
      mM KCI or media and fixed at 0, 0.5, 1, 2, and 4 h posttreatment. Sequential
      immunocytochemistry was performed to identify Fos immunoreactivity in tyrosine
      hydroxylase (TH)-immunoreactive (-ir) or oxytocin (OT)-ir neurons. Activated
      neurons [brown cells (TH-ir or OT-ir) with purple nuclei (Fos-ir)] were counted
      microscopically. KCI treatment resulted in an increased percentage of Fos-ir TH
      ir and OT-ir neurons over control levels over the time course examined. Fos-ir
      peaked in TH-ir neurons at 0.5 to 1 h posttreatment, with levels returning to
      baseline at 4 h. Fos-ir in OT-ir neurons peaked at 2 h, and remained elevated at
      4 h, showing prolonged activation. These results demonstrate that KCI-induced
      depolarization of cultured hypothalamic neurons increases Fos with a different
      time course in TH-ir vs. OT-ir neurons.

PMID- 7712201
TI  - 8-OH-DPAT-induced hypotensive action and sympathoexcitatory neurons in the
      rostral ventrolateral medulla of the rat.
AB  - We examined whether the selective 5-hydroxytryptamine 1A (5-HT1A) receptor
      agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) injected systemically
      can act directly on sympathoexcitatory neurons located in the rostral
      ventrolateral medulla (RVLM) to cause the hypotensive effect of this agent in
      rats. Microinjections of 8-OH-DPAT and buspirone into the RVLM produced a dose
      dependent decrease in blood pressure. Microinjections of spiperone and pindolol,
      5-HT1A antagonists, into the RVLM inhibited the depressor response to 8-OH-DPAT
      intravenously injected or injected into the RVLM. Microiontophoretic application
      of 8-OH-DPAT onto RVLM sympathoexcitatory neurons inhibited the firing of RVLM
      sympathoexcitatory neurons and the inhibition of unit activity by 8-OH-DPAT was
      blocked by microiontophoretic spiperone. Intravenous administration of 8-OH-DPAT
      also inhibited the firing of these neurons. Microiontophoretic application of
      spiperone onto the RVLM sympathoexcitatory neurons reversed the inhibitory
      response to intravenous 8-OH-DPAT. These results are consistent with the
      hypothesis that 8-OH-DPAT may exert a portion of its hypotensive effect through a
      direct inhibition of RVLM sympathoexcitatory neurons in rats. The receptor
      involved is probably the 5-HT1A type.

PMID- 7712202
TI  - Absence of short-loop autoregulation of prolactin during late pregnancy in the
      rat.
AB  - Animals bearing intrahypothalamic anterior pituitary (AP) grafts exhibit a
      central hyperprolactinemia, and thus, serve as a model for the study of short
      loop feedback regulation of prolactin (PRL) secretion. We investigated the
      effects of intrahypothalamic AP grafts on PRL secretion during late pregnancy (n
      = 7). A further group of five rats was injected with the dopamine against
      bromocriptine during late pregnancy and five control rats were treated with the
      bromocriptine-vehicle only. A nocturnal surge in plasma PRL concentrations was
      observed in the vehicle-injected control animals, peaking at 212 +/- 11 ng/ml at
      0300 h on the day of parturition. Despite the central hyperprolactinemia due to
      the grafts, a similar PRL surge was observed in grafted animals, peaking at 205
      +/- 35 ng/ml at 0300 h on the day of parturition. Bromocriptine treatment
      completely blocked the nocturnal surge of PRL. These results suggest that short
      loop feedback autoregulation of PRL secretion becomes less responsive or
      nonfunctional in the last 24 h of pregnancy in the rat. This apparent change in
      sensitivity of the autofeedback mechanism may be an important physiological
      mechanism to allow the hypersecretion of PRL during lactation.

PMID- 7712203
TI  - Continuous systemic interleukin-1 alpha infusion suppresses food intake without
      increasing lateral hypothalamic dopamine activity.
AB  - In addition to its immunomodulatory action, interleukin-1 (IL-1 alpha) induces
      anorexia centrally. Whether IL-1-induced anorexia is mediated by dopaminergic
      activity in the lateral hypothalamic area (LHA) was investigated by using
      microdialysis in freely moving rats. After recovery from jugular vein
      catheterization and LHA cannulation, rats had a microdialysis probe inserted into
      the LHA. Microdialysis samples were continuously collected in control rats not
      infused, and in IL-1-treated rats during and after a 24 h continuous systemic
      infusion of 6 micrograms IL-1 alpha. IL-1 alpha significantly suppressed food
      intake from 13.6 +/- 0.1 g to 4.3 +/- 0.8 g (p < 0.001), but there was no
      significant difference in dopamine concentration in the LHA dialysates before,
      during and after IL-1 alpha infusion relative to controls. Although IL-1 alpha
      has been shown to act centrally, our results suggest that the anorexic effect of
      IL-1 alpha is not mediated through dopaminergic activity in the LHA.

PMID- 7712204
TI  - An NMDA receptor antagonist reduces ethanol preference in untrained but not
      trained rats.
AB  - Rats were exposed to a potent antagonist of NMDA receptors, 2-amino-5
      phosphonovalerate (AP5) by implanting osmotic pumps delivering AP5 (test group)
      or the vehicle for AP5 (control group) into the cerebrospinal fluid through
      previously implanted cannulas. A week later they were given the choice of 6%
      ethanol or water for 1 h. The control group had a significantly greater
      preference for ethanol than the test group after the first 5 days. Another group
      of rats was trained almost to a 100% criterion in preferring ethanol to water in
      the hour the choice was available. Then they were implanted with osmotic pumps
      and cannulas and administered AP5. These trained rats showed no significant
      difference between control and test groups in preference for ethanol after the
      first 5 days. The results support the hypothesis that activation of NMDA
      receptors is involved in learning to drink ethanol.

PMID- 7712205
TI  - Glial cell line-derived neurotrophic factor augments midbrain dopaminergic
      circuits in vivo.
AB  - Recently, a novel glial cell line-derived neurotrophic factor (GDNF) has been
      identified, cloned, and shown to have potent survival- and growth-promoting
      activity on fetal rat midbrain dopaminergic neurons in cell culture. In this
      study, we document marked and long-lasting effects on adult rat midbrain
      dopaminergic neurons in vivo after intracranial administration. A single
      injection of this factor into the substantia nigra elicited a dose-dependent
      increase in both spontaneous and amphetamine-induced motor activity, and a
      decrease in food consumption, lasting 7-10 days. Using immunocytochemistry, we
      found sprouting of tyrosine hydroxylase-positive neurites towards the injection
      site, and increased tyrosine hydroxylase immunoreactivity of the ipsilateral
      striatum was produced by GDNF. There was also a marked and dose-dependent
      increase in dopamine turnover in the substantia nigra and striatum, and in
      ipsilateral dopamine levels in the substantia nigra. Little or no effects of GDNF
      were seen on norepinephrine or serotonin levels. The neurochemical changes on
      dopaminergic afferents persist for at least 3 weeks after a single intracranial
      injection of 10 micrograms. Taken together, these data suggest that this glial
      cell line-derived factor has a potent influence on adult rat dopamine neurons and
      may have a potentially important role as a trophic factor for these neurons.

PMID- 7712206
TI  - Distribution of neurotransmitters, neuropeptides, and receptors in the vestibular
      nuclei complex of the rat: an immunocytochemical, in situ hybridization and
      quantitative receptor autoradiographic study.
AB  - This article investigates the distribution of neurotransmitters, neuropeptides,
      and related receptors in the vestibular nuclei complex (VNC) of the adult rat by
      means of immunohistochemistry, in situ hybridization, and quantitative receptor
      autoradiography. The entire complex proves to be rich in muscarinic receptors and
      it shows a high density of imipramine and benzodiazepine binding sites.
      Peptidergic neurons and a few positive fibers are described in the caudal part of
      the VNC. In particular, the medial vestibular nucleus contains a number of
      neurons expressing both the enkephalin mRNA and peptide. This nucleus and the
      lateral vestibular nucleus are also rich in opiate receptors. Substance P,
      thyrotropin releasing hormone, and neurotensin receptors are also found in the
      medial and in the spinal vestibular nuclei. In spite of the presence of alpha 2
      catecholaminergic receptors, no thyrosine-hydroxylase-immuno-reactive elements
      are seen in the caudal VNC. The possible functional meaning of these data is
      discussed.

PMID- 7712207
TI  - Age-related changes in brain microanatomy: sensitivity to treatment with the
      dihydropyridine calcium channel blocker darodipine (PY 108-068).
AB  - The influence of aging and of treatment with the dihydropyridine Ca2+ antagonist
      darodipine (PY 108-068) on the age-related microanatomical changes of rat brain
      were studied in male Wistar rats treated from the 18th to the 24th month of age
      with an oral dose of 5 mg/kg/day of darodipine. Twelve-month-old untreated rats
      were used as an adult reference group. A decreased number of nerve cells and of
      alkaline phosphatase-positive capillaries and an increased lipofuscin deposition
      were observed in the frontal and occipital cortex, in the hippocampus, and in the
      cerebellar cortex of rats of 24 months in comparison with 12-month-old animals.
      The number of nerve cells was higher in the occipital cortex and in the
      hippocampus, but not in the frontal cortex and in the cerebellar cortex, of
      darodipine-treated rats in comparison with age-matched untreated animals.
      Lipofuscin deposition is reduced in all the brain areas investigated. The density
      of alkaline phosphatase-reactive capillaries is also increased in the frontal and
      occipital cortex and in the hippocampus of aged rats treated with darodipine. The
      above results suggest that treatment with darodipine is able to counter some
      microanatomical changes occurring in the brain of aged rats and involving not
      only microvascular parameters. The occipital (visual) cortex and the hippocampus
      were the cerebral areas more sensitive to treatment with darodipine. The possible
      relevance of these findings is discussed.

PMID- 7712208
TI  - In vitro effects of GABA and hypoxia on posterior hypothalamic neurons from
      spontaneously hypertensive and Wistar-Kyoto rats.
AB  - Recent studies from this laboratory have shown that neurons in this hypothalamic
      region are stimulated by hypoxia in vivo and in vitro. In addition, GABAergic
      activity is depressed in the posterior hypothalamus of the spontaneously
      hypertensive rat compared to the normotensive rat. The major purposes of the
      present study were to: a) evaluate if posterior hypothalamic neurons respond
      differently to GABA in the hypertensive rat compared to the normotensive rat; and
      b) examine the possibility that hypothalamic neurons from spontaneously
      hypertensive rats respond differently to hypoxia than those from normotensive
      rats. In addition, the effects of GABA on hypoxia-sensitive neurons was recorded.
      Extracellular single unit recordings of hypothalamic neurons were performed in a
      rat brain slice preparation. Neuronal responses to hypoxia (10% O2/5% CO2/85% N2)
      and to GABA were recorded from slices taken from both Wistar-Kyoto (WKY) and
      spontaneously hypertensive (SHR) rats. Administration of three different
      concentrations of GABA evoked a dose-related decrease in discharge rate in
      similar percentages of neurons from both SHR and WKY rats. The magnitude of the
      depression elicited by GABA did not differ significantly between the neurons from
      SHR and WKY rats. Hypoxia increased the firing rate of 75% and 69% of the SHR and
      WKY neurons, respectively; no differences (p > 0.05) were noted in the magnitude
      of the response or in the percentage of neurons responding to hypoxia between the
      two strains of rats. The discharge rate of most of these neurons fell to below
      control level following removal of the hypoxic stimulus. A significant percentage
      of SHR (75%) and WKY (75%) neurons that were stimulated by hypoxia were inhibited
      by exogenously applied GABA. These results indicate that a) an altered
      sensitivity of hypothalamic neurons to GABA does not contribute to hypertension
      in the SHR and b) the depressed respiratory response to hypoxia in the SHR is not
      due to a decreased responsiveness of hypothalamic neurons to hypoxia.

PMID- 7712209
TI  - Extensive brain mapping of calcitonin-induced anorexia.
AB  - The purpose of this study was to compare the localization in the brain of
      calcitonin-induced anorexia to the distribution of calcitonin binding sites (as
      described by others). We, thus, performed an extensive mapping of brain
      structures to determine those involved in calcitonin-induced anorexia. A
      significant anorexia is found after injection of calcitonin (15 ng in 0.3
      microliters) into several brain areas. Forebrain: lateral septum, lateral part of
      the anterior commissure, and bed nucleus of the stria terminalis; hypothalamus:
      floor of the anterior part of the hypothalamus, paraventricular nucleus and
      adjacent perifornical area; thalamus: nucleus reuniens, an area internal to the
      mamillo-thalamic tract, and medial geniculate body; other areas: amygdala,
      lateral hippocampus, and central gray. No significant effect is found in the
      following areas: forebrain: nucleus accumbens, striatum, and medial septum;
      hypothalamus: lateral, ventro-medial, dorso-medial, and posterior nuclei;
      thalamus: centro-medial nucleus, lateral part of the zona incerta, and lateral
      geniculate body; hippocampus: dorsal and ventral parts; midbrain: central
      tegmentum, ventral tegmental area, and substantia nigra. When these results are
      compared to the distribution of calcitonin binding sites in the brain, two types
      of discrepancies are found. The first is the absence of effect in areas
      containing receptors: these areas may be involved in calcitonin-induced behaviors
      other than food intake. The second is the occurrence of anorexia in areas where
      no receptors are found: this finding is not easy to explain and raises some
      speculative hypotheses. In conclusion, calcitonin is active to decrease food
      intake in several brain areas, the strongest effect occurring in the
      paraventricular/perifornical area.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712210
TI  - Cross generation lead ingestion: behavioral and physiological effects in mice.
AB  - We examined some developmental and behavioral sequelae of exposing Binghamton
      Heterogeneous Stock (HET) mice to a 0.5% aqueous lead acetate solution (as the
      only available fluid source) for either none, one, two, or three generations.
      Lead exposure, regardless of generation, resulted in decreased body weight and a
      delay in age of first eye opening relative to controls, but did not delay home
      nest return latencies. Drinking the lead solution, across two and three
      successive generations, resulted in a marked and apparently cumulative decrease
      in pup viability, as well as an increase in dam fatality rates. However, no such
      cumulative or residual effects were observed on the behavioral activity of those
      mice who managed to survive. Perhaps a selection effect for lead-tolerant mice
      occurred in the present study; such an effect could account for the apparent lack
      of cumulative and residual behavioral effects.

PMID- 7712211
TI  - Role of nitric oxide in modulating neurotransmitter release from rat striatum.
AB  - The effect of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester
      (L-NAME) on the basal and stimulation-evoked release of dopamine (DA) and
      acetylcholine (ACh) was investigated in rat striatum. The experiments were
      carried out in isolated superfused striatal slices, loaded with either [3H]
      dopamine or [3H]-choline. We have found that L-NAME reduced the electrical field
      stimulation-evoked release of DA, while its enantiomer N-nitro-D-arginine methyl
      ester (D-NAME) was ineffective. In the presence of the nitric oxide (NO)
      precursor L-arginine, L-NAME failed to influence DA release. Furthermore,
      treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801
      completely reversed the effect of L-NAME on striatal DA release. In contrast, L
      NAME had no effect on either the basal or the stimulation-evoked ACh release in
      any experimental conditions studied. Our data indicate that endogenously produced
      NO is involved in the modulation of striatal DA, but not in ACh release.
      Furthermore, it seems likely that the modulatory effect of NO is linked to
      activation of presynaptic NMDA receptors located on the striatal dopaminergic
      nerve terminals.

PMID- 7712213
TI  - The GABAB antagonist CGP 35348 inhibits the effects of baclofen on sexual
      behavior and motor coordination.
AB  - The intraperitoneal injection of 100 mg/kg of CGP 35348 completely blocked the
      effects of 2.5 mg/kg of (R)-baclofen on sexual behavior and motor coordination in
      male rats. Doses of 50 and 25 mg/kg partially blocked the effects of (R)-baclofen
      on sexual behavior but not those on motor coordination. The antagonist itself had
      no effect on these behaviors. These observations confirm previous data suggesting
      that the inhibitory effect of (R)-baclofen on sexual behavior is not only a
      consequence of motor deficiencies and indicates that this effect is due to an
      action at GABAB receptors. The lack of effect of CGP 35348 on sexual behavior
      when the drug was administered alone may suggest that GABAB receptors are not
      important for the physiological control of sexual behavior.

PMID- 7712212
TI  - Eating induced rise in LHA-dopamine correlates with meal size in normal and
      bulbectomized rats.
AB  - Dopaminergic function in the lateral hypothalamic area (LHA) is important for
      processing intrinsic and extrinsic feeding related information. Brain
      microdialysis was used to examine if dopamine release in the LHA correlates with
      meal size in normal and bulbectomized rats. Food-deprived bulbectomized rats ate
      significantly less food (1.7 +/- 0.1 g) than food-deprived sham operated rats
      (3.1 +/- 0.5 g, p < 0.05), accompanied by a lesser increase in LHA-dopamine
      release (150.6 +/- 4.9% vs. 195.1 +/- 13.9, p < 0.02). LHA-dopamine release was
      significantly higher in rats which ate a full meal (2.9 +/- 0.1 g) than in rats
      which ate half a meal (1.5 +/- 0.1 g, p < 0.05), being 155.9 +/- 7.8% vs. 131.0
      +/- 4.9% (p < 0.05) in food-deprived normal rats. Data suggest that dopamine
      release in the LHA correlates to the quantity of food consumed during a meal.

PMID- 7712214
TI  - Learning and retention of a visual discrimination task in rats with various
      combinations of lesions in the temporal-hippocampal region.
AB  - The temporal-hippocampal region appears to be critically involved in cognitive
      functions. Hippocampal or parahippocampal lesions have been reported to impair
      learning and memory. Radical hippocampal lesions may, however, encroach upon the
      neighboring parahippocampal cortex, and the effects obtained are often attributed
      to hippocampal dysfunction alone. The present study was undertaken to examine
      whether damage to neighboring structures along with the hippocampus might have
      additive disruptive effects on learning and memory. Rats received either
      selective hippocampal (hippocampus proper, fascia dentata, subiculum) lesions
      alone or hippocampal lesions (Hipp) combined with damage to the temporal cortex
      (TC), the lateral entorhinal cortex (LEC), or the fiber connections between TC
      and LEC. Hipp lesions alone resulted in only impairment of the acquisition of a
      visual discrimination task, whereas Hipp + LEC lesions and Hipp + TC/LEC lesions
      produced marked deficits in both acquiring and retaining the same task. Hipp + TC
      lesions caused a milder impairment of both acquisition and retention. These
      results suggest that profound effects on learning and memory can be obtained when
      hippocampal lesions are combined with parahippocampal lesions.

PMID- 7712215
TI  - Bitterness of sweeteners as a function of concentration.
AB  - Sixteen trained tasters provided sweetness and bitterness intensity ratings for
      19 compounds including: acesulfame-K, alitame, aspartame, fructose, glucose,
      glycine, lactitol, maltitol, monoammonium glycyrrhizinate, neohesperidin
      dihydrochalcone, neosugar (fructo-oligosaccharide), palatinit (isomalt),
      rebaudioside-A, sodium cyclamate, sodium saccharin, stevioside, sucralose,
      sucrose, and thaumatin. With increasing concentration, high-potency sweeteners
      including acesulfame-K, neohesperidin dihydrochalcone, sodium saccharin,
      rebaudioside-A, and stevioside tended to become more bitter. Low-potency
      sweeteners including fructose, sucrose, and lactitol tended to become less bitter
      with increasing concentration.

PMID- 7712216
TI  - Another human interest story.

PMID- 7712217
TI  - Children in accident and emergency: parental perceptions of the quality of care.
      Part I.
AB  - An exploratory descriptive survey of the perceptions of parents of children
      attending an Accident and Emergency department is described. The study examines
      parental perceptions of the quality of care received, and explores whether this
      sphere of patient care requires further attention. A retrospective postal
      questionnaire was administered to parents of children, under the age of 10,
      attending the department. Follow-up interviews were also conducted, allowing
      further exploration of the issues affecting the parents' perceptions of care. The
      study confirmed the usefulness of auditing parents' perceptions of care. Quality
      aspects of care were highlighted, with lack of information and communication
      patterns shown to affect the perceived standard of care.

PMID- 7712218
TI  - What to do if called upon to testify.
AB  - There are fundamental differences in the healthcare delivery systems, cultural
      ideologies, and legal procedures for malpractice litigation among the US, UK and
      Australia. Nursing malpractice litigation is definitely on the increase in the
      US. Evidence shows that this same trend is beginning in Australia and the UK.
      This article addresses some of the reasons for this increase in litigation, and
      identifies actions that a nurse can undertake to prepare for a deposition or
      court testimony if called upon to do so.

PMID- 7712219
TI  - Physical environmental factors affecting patients' stress in the accident and
      emergency department.
AB  - This study is concerned with the physical environment of our Accident and
      Emergency (A & E) departments, with reference to added stressors that may affect
      our clients' overall experience of A & E. It will hopefully highlight an
      awareness of the environment and what we, as nurses, can do to enhance a
      therapeutic, humanised department that will not only help our clients cope, but
      in turn will assist the delivery and reception of our care. The functional
      purpose of our departments are paramount; however, must we totally ignore the
      aesthetic values of a humanised environment that will have a positive effect on
      its user groups? Cost is one factor which will probably spring to mind, however
      heightening awareness will initiate the process of change that will help
      establish rationales for change. There is not enough input from nurses with
      regard to environmental studies, or inclusion in the planning of our departments.
      If more is done then we can achieve even higher standards of care and a more
      positive thought/memory of A & E.

PMID- 7712220
TI  - Accident and emergency monitor.
AB  - This paper describes the development of a set of practical quality audit criteria
      relevant to the examination of nursing care delivered to patients and relatives
      in hospital Accident and Emergency (A & E) departments. The project was initiated
      by senior nurse managers at the North Staffordshire Royal Infirmary, UK,
      conducted in partnership with Leeds Polytechnic (now the Leeds Metropolitan
      University), UK, and received further sponsorship from the Royal College of
      Nursing Accident and Emergency Association.

PMID- 7712222
TI  - An exploration of family-centred care in Neuman's model with regard to the care
      of the critically ill adult in an accident and emergency setting.
AB  - In Accident and Emergency (A & E) departments there is a tendency to separate
      relatives from critically ill patients, and although in many departments the
      relatives have a nurse allocated to care for them, this care is often given in a
      separate 'relatives' room. This article explores the meanings of family, family
      nursing and family systems nursing in the context of an A & E setting and using
      Neuman's (1989) model to highlight family dynamics. The intention is to allow the
      thinking A & E nurse to reflect on care given in the department, so that
      individualised care can be given with consideration to the relationships that the
      person has before they take on the status of 'patient'. Thus, the article is
      meant to be thought-provoking rather than prescriptive.

PMID- 7712221
TI  - Pain relief in accident and emergency?
AB  - A recent audit on fractured neck of femurs in our department highlighted our poor
      pain management. While I was undertaking a PS II module on 'Understanding and
      Managing Pain' there was an abundance of literature on pain management in other
      specialties but I was disappointed at the lack of literature on pain management
      pertaining to Accident and Emergency (A & E). This made me more aware of the low
      priority that pain management is given in A & E. This paper looks at the pain
      management of two different patients in my department and how staff's perception
      of their pain affected their subsequent management. The response from both
      medical and nursing staff at improving pain management has been favourable but
      everybody realises that it will be a gradual process--it can't happen overnight.

PMID- 7712223
TI  - Death in accident and emergency.
AB  - Death can often be distressing but when it occurs in the Accident and Emergency
      (A & E) department it is often accompanied by the involvement of police and the
      coroner. It is essential that nurses have a sound understanding of the legal
      situation, so that they can advise relatives appropriately and so that they know
      clearly the appropriate practice and procedures to prevent further difficulties.
      This article seeks to set down some of the basic principles and looks at some
      situations which can cause anxiety to nursing staff.

PMID- 7712224
TI  - What is in a name?

PMID- 7712225
TI  - Pre-hospital care--current concepts.
AB  - After a brief outline of past developments in the training of ambulance
      personnel, this paper traces the adoption in the UK of Pre-Hospital Trauma Life
      Support (PHTLS) courses from the US. The 1991 World Student Games in Sheffield,
      UK led to liaison between training staff from South Yorkshire Metropolitan
      Ambulance and Paramedic Service (SYMAPS) and from Western New York Medical
      Training Institute. As a result, the trauma care policy of SYMAPS was altered
      from aiming to stabilise the patient at the scene of the accident to emphasising
      rapid and thorough assessment, packaging and transport. This is a resume of the
      scope of the PHTLS provider course. The course concentrates on the principles of
      PHTLS for the multisystems trauma victim.

PMID- 7712226
TI  - Accident and emergency with Ambie Bear.

PMID- 7712227
TI  - To do or not to do: use of the scope of professional practice in accident and
      emergency work.
AB  - The Scope of Professional Practice has the potential to revolutionise the
      practice of Accident and Emergency nursing. However, for such a revolution to
      take place re-evaluation of the thinking and doing of Accident and Emergency
      nursing is needed. In particular, many organisational approaches to work such as
      team-building and multidisciplinary work need to be recognised and the place of
      the nurse within them formalised. The make-up of nurses' work in Accident and
      Emergency needs to be understood, so that expansion of the role can encompass a
      wide range of 'caring' work as well as easily identify tasks. In addition the use
      of the Scope of Professional Practice should be based upon clarification and
      recognition of dilemmas which may lead to informed risk taking by Accident and
      Emergency nurses. Once nurses' work in Accident and Emergency is understood, the
      short- and long-term effects on the continuity of patient and family care of
      nurses' actions and non-action can be explored. Communication is seen as
      underpinning all professional and care development in relation to the use of the
      Scope of Professional Practice in Accident and Emergency. The art of listening as
      well as talking to colleagues, patients and families is important if the
      revolution is to take place.

PMID- 7712228
TI  - The association between HIV phenotype, virus burden, codon 215 mutation and CD4
      cell decline.

PMID- 7712229
TI  - Acute feline leukemia virus infection causes altered energy balance and growth
      inhibition in weanling cats.
AB  - Naturally occurring retroviral infections cause progressive weight loss, immune
      suppression, invasion by opportunistic organisms, and eventual death. Feline
      leukemia virus (FeLV) inhibited growth and decreased energy intake in seven
      experimentally infected weanling cats compared with age- and sex-matched
      controls. Remarkably, changes in energy intake, energy expenditure, and weight
      gain occurred in the acute phase of infection prior to the systemic/productive
      bone marrow phase of FeLV infection. In other words, growth inhibition developed
      before FeLV infection was clinically detectable with use of standard enzyme
      linked immunosorbent assay or fixed-cell immunofluorescence assays of circulating
      neutrophils and platelets. Acutely infected, previremic cats consumed 25% less
      energy [Day 4 postinoculation to Day 16 postinoculation (p < 0.05)] and expended
      20% less energy [Day 8 postinoculation to Day 18 postinoculation (p < 0.05)]
      compared with control cats. Growth stunting of inoculated cats began by Day 11
      postinoculation (p < 0.05) and was not corrected during the remaining 4 months of
      the study. Thus, experimental FeLV infection causes perturbations of metabolism
      and energy balance resulting in permanent growth impairment. Secondly,
      detrimental metabolic effects begin in the acute phase of retroviral infection,
      prior to the clinically detectable phase of FeLV infection.

PMID- 7712230
TI  - Bioelectrical impedance analysis as a predictor of survival in patients with
      human immunodeficiency virus infection.
AB  - In patients with AIDS, short-term survival has been related to body weight, body
      composition, and serum nutritional parameters, but their prognostic impact at
      earlier stages of the HIV infection is not known. With an individual follow-up
      period of 1,000 days, we investigated the prognostic relevance of electrical
      tissue conductivity [resistance R, reactance Xc, phase angle alpha, extracellular
      mass (ECM), body cell mass (BCM)] measured by bioelectrical impedance analysis,
      of the CD4+ cell count, and of serum parameters indicating malnutrition in 75 HIV
      infected male patients at Walter Reed stages 3-5. After initial recording, 29
      patients (38.7%) died from AIDS during this period. Among 12 parameters estimated
      with a semiparametric Cox regression model adjusted for therapy (pentamidine,
      azidothymidine), the phase angle alpha (parameter estimate: -1.043, 95%
      confidence interval of -0.61 to -1.47; p < or = 0.0001), the ECM/BCM ratio, Xc,
      BCM, serum cholesterol, number of CD4+ cells, and serum albumin had significant
      prognostic influence on survival, whereas age, body weight, body mass index,
      resistance, serum protein, and serum triglycerides did not. In a model with four
      covariates (CD4+ cells, phase angle, pentamidine, azidothymidine), the prognostic
      impact of the CD4+ cell count (parameter estimate: -0.549) was lower compared
      with the phase angle alpha (parameter estimate: -0.799; p < or = 0.0001) and did
      not gain statistical significance (p = 0.0626). The phase angle alpha was the
      best single predictive factor for survival among all 12 parameters (comparison of
      the respective Cox models with the likelihood ratio test).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7712231
TI  - The rocky road to an AIDS vaccine.

PMID- 7712232
TI  - Strategies for addressing the social and behavioral challenges of prophylactic
      HIV vaccine trials.

PMID- 7712233
TI  - Incentives and disincentives to participate in prophylactic HIV vaccine research.
AB  - An anonymous cross-sectional paper-and-pencil survey was used to assess
      incentives and disincentives to participate in a Phase I preventive human
      immunodeficiency virus (HIV) vaccine trial in a potential Thai target population.
      A total of 255 persons employed in health care service and research settings
      completed questionnaires after attending informational briefings regarding the
      proposed vaccine product and the planned trial procedures. Willingness to
      participate was related to self-perceived benefits from joining a preventive
      vaccine trial, as well as to concerns about product safety and social
      discrimination that might result from participation. The distinction between
      positive results of enzyme-linked immunosorbent assay from vaccine administration
      and positivity from HIV infection was unclear for many participants. Men were
      more willing to participate than women, and there was a trend toward greater
      willingness to participate in those who were less educated. Preparations for
      preventive vaccine trials may be more successful if they emphasize personal
      benefits of trial participation, clearly address safety issues, and consider ways
      to prevent social discrimination against participants.

PMID- 7712234
TI  - Predictors of HIV disease progression in women.
AB  - A retrospective cohort study was conducted to analyze variables predictive of
      acquired immunodeficiency syndrome (AIDS), as defined by the Centers for Disease
      Control (CDC) in 1987, and death in 224 women infected with the human
      immunodeficiency virus (HIV) who were evaluated through two HIV outpatient
      programs in New Orleans between January 1987 and December 1991 and followed
      through February 1993. Variables predictive of AIDS in a multivariate
      proportional hazards model were an entry CD4 cell count < 200/mm3 (adjusted RR
      8.2, 95% CI 3.2, 20.9) and rapid CD4 cell count decline (adjusted RR 6.0, 95% CI
      2.4, 15.5). A baseline AIDS diagnosis (by the CDC 1987 definition) was highly
      predictive of death (RR 36.3, 95% CI 15.7, 70.1). In multivariate analyses none
      of the relative risks for predictive variables remained significant if adjusted
      for a diagnosis of AIDS at entry. Although immunological parameters were
      predictive of early HIV disease progression, an AIDS diagnosis was the strongest
      prognostic indicator of death in a cohort of North American women.

PMID- 7712235
TI  - Transient high titers of HIV-1 in plasma and progression of disease.
AB  - Periodic quantitative HIV-1 plasma cultures were performed on 28 seropositive
      individuals who had CD4 cells < or = 300/mm3 and who were enrolled in three
      clinical trials testing the efficacy of didanosine versus zidovudine monotherapy.
      Most plasma cultures were negative or of low titer (1-100 tissue culture
      infective dose/ml of plasma), but there were 14 instances of high-titered plasma
      viremia (> or = 1,000 tissue culture infective dose/ml of plasma) seen in 11
      individuals. These peaks in plasma culture titers were significantly associated
      either with rapidly decreasing CD4 cell numbers or with CD4 cells already <
      50/mm3. In addition, patients who experienced these episodes of high-titered
      plasma viremia were more apt to have clinical complaints of fever, rash, flu-like
      illness, and/or opportunistic infection and also the syncytium-inducing HIV-1
      phenotype and progression of disease.

PMID- 7712236
TI  - Active human herpesvirus (HHV-6) infection of the central nervous system in
      patients with AIDS.
AB  - White matter disease is a relatively common neuropathological change observed in
      the central nervous system (CNS) tissues of patients with AIDS at autopsy. This
      disease ranges from small foci of myelin loss to extensive areas of
      demyelination. In the studies reported here, four of six unselected adult
      patients with AIDS had areas of demyelination in their CNS tissues at the time of
      their deaths. In the tissues examined, the severity of the demyelinative disease
      varied among the patients from a single focus of demyelination to essentially
      confluent loss of myelin in subcortical white matter and other CNS structures.
      The demyelinative disease in the brains of these patients was closely associated
      with active HHV-6 infection. The infected cells were present only in areas of
      demyelination, and they were never observed in tissue areas free of pathological
      changes. The HHV-6-associated neuropathology observed in the brains of these
      patients was identical to that described in an adult bone marrow transplant (BMT)
      patient with fatal HHV-6 encephalitis. Thus HHV-6-induced white matter disease
      appears to be a distinct pathological syndrome. Pathogenic mechanisms involved in
      this disease are unknown. However, the existence of HHV-6 leukoencephalopathy in
      a BMT patient demonstrates the potential for HHV-6 leukoencephalopathy in a BMT
      patient demonstrates the potential for HHV-6 to cause this syndrome without need
      for a cofactor or copathogen such as HIV.

PMID- 7712237
TI  - Recent trends in Pneumocystis carinii pneumonia as AIDS-defining disease in nine
      European countries. Coordinators for AIDS Surveillance.
AB  - We analyzed the proportion of AIDS cases with Pneumocystis carinii pneumonia
      (PCP) at diagnosis among the 43,198 adult AIDS cases diagnosed since January 1988
      and reported by June 1992 in Austria, Belgium, France, Germany, Italy, Portugal,
      Switzerland, United Kingdom, and the city of Amsterdam. In multivariate analysis,
      the risk of having PCP at AIDS diagnosis decreased slightly with increasing age
      and was strongly associated with country of diagnosis, transmission category, and
      year of diagnosis, but not with gender. Since 1989, the proportion of AIDS cases
      with PCP decreased significantly among homosexual and bisexual men in five of the
      nine countries examined and among injecting drug users in four of seven
      countries. In three countries with sufficient data for analysis, no significant
      decrease was seen among heterosexual patients with a partner originating from a
      country where heterosexual transmission is common (i.e., Africa/Caribbean). Among
      other heterosexual patients, a significant decreasing trend was demonstrated in
      only one of six countries analyzed. For all countries combined, the decrease was
      significant among hemophiliacs and of borderline significance among transfusion
      recipients. Results suggest that medical management before AIDS diagnosis is not
      homogeneous among all human immunodeficiency virus (HIV)-infected persons in
      Europe. Efforts should be made to provide better information on the potential
      benefit of early HIV testing and to facilitate the use of preventive treatments.

PMID- 7712238
TI  - Risk factors for HTLV-I among heterosexual STD clinic attenders.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-I) status was assessed in 994
      patients attending a sexually transmitted disease (STD) clinic in Kingston,
      Jamaica, between November 1990 and January 1991 for a new STD complaint. Of 515
      heterosexual men, 36 (7.0%) were HTLV-I seropositive, as were 38 (7.9%) of 479
      women. HTLV-I seroprevalence increased with age in women. A history of blood
      transfusion was associated with HTLV-I in both sexes, significantly so in men
      [odds ratio (OR) 4.7, confidence interval (CI) 1.1-17 for men; OR 1.9, CI 0.6-5.0
      for women]. Further analysis excluded all persons reporting a transfusion. On
      multiple logistic regression analysis, independent associations with HTLV-I
      infection in men were shown for marital status (OR 3.5, CI 1.2-10 for
      married/common law vs. single/visiting unions), agricultural occupation (OR 9.0,
      CI 2.0-41), bruising during sex (OR 2.9, CI 1.0-8.1), > or = 15 years at first
      sexual intercourse (OR 2.9, CI 1.0-8.2), and a positive test for hepatitis B
      surface antigen (OR 7.3, CI 1.2-52). In women, associations were shown for two or
      more sex partners in the 4 weeks prior to complaint (OR 4.9, CI 1.8-13), 11 or
      more lifetime sexual partners (OR 5.9, CI 1.3-27), aged < 15 years at first
      sexual intercourse (OR 2.3, 1.0-5.4), bruising during sex (OR 2.7, CI 1.1-6.6),
      microhaemagglutination-Treponema pallidum positivity (OR 3.6, CI 1.6-8.4), and
      human immunodeficiency virus infection (OR 14, CI 2.1-92).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7712239
TI  - Incidence and risk factors for human T-lymphotropic virus type II seroconversion
      among injecting drug users in Baltimore, Maryland, U.S.A.
AB  - To determine the incidence of and risk factors for human T-lymphotropic virus,
      type II (HTLV-II) seroconversion among injecting drug users (IDUs), specimens
      from IDUs recruited into the ALIVE Study in 1988/1989 were assayed at baseline
      for antibody to HTLV with use of enzyme immunoassay and Western blot.
      Participants were monitored semiannually with venipuncture and interviews. In
      1992, the most recent sera of HTLV-negative participants were tested for HTLV
      with use of enzyme immunoassay and confirmed and typed by Western blot. For
      positive cases, assays were then performed for all intervening visits to
      determine the calendar time of seroconversion. Incidence rates were estimated
      using person-time. Risk factor analysis used a nested case-control design, with
      up to seven controls per case matched by time of study entry and duration of
      follow-up. At baseline, 251 HTLV-positive, 22 indeterminate, and 2,574 HTLV
      seronegative IDUs were identified. Follow-up of the seronegative IDUs identified
      38 seroconverters (all HTLV-II) over 5,813.6 person-years, for a rate of 0.7/100
      person-years. Median lag time for seroconversion was 6.8 months. Factors
      associated with HTLV-II seroconversion included a specific needle-sharing
      practice called "backloading" within the previous 6 months [odds ratio (OR) =
      6.52; 95% confidence interval (CI) = 1.94-21.95] and a baseline history of
      receiving money for sex (OR = 3.36; 95% CI = 1.32-8.57). Of those with more than
      one sex partner in the past 6 months, women were more likely than men to
      seroconvert (OR = 5.77; 95% CI = 1.33-25.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712240
TI  - Lack of short-term efficacy of N-acetyl-L-cysteine in human immunodeficiency
      virus-positive patients with CD4 cell counts < 250/mm3.

PMID- 7712241
TI  - Diabetes insipidus and AIDS.

PMID- 7712242
TI  - Absence of evidence for human spumaretrovirus sequences in patients with Graves'
      disease.

PMID- 7712243
TI  - Psychiatrists are physicians.

PMID- 7712244
TI  - Reliability of sexual risk behavior interviews on an alcohol rehabilitation unit.

PMID- 7712245
TI  - Use of OBRA-87 guidelines for prescribing neuroleptics in a VA nursing home.

PMID- 7712246
TI  - Setting capitation rates for comprehensive care of persons with disabling mental
      illness.

PMID- 7712247
TI  - HIV-related cases among 2,094 admissions to a psychiatric hospital.
AB  - OBJECTIVE: Admissions to an acute care psychiatric hospital were studied to
      determine what proportion of admissions were for HIV-related psychiatric
      disturbances, what evidence exists that the HIV-related admissions constitute a
      new population of psychiatric inpatients, and whether any psychiatric variables
      distinguish patients with HIV-related disorders from patients without such
      disorders. METHODS: Charts for 2,094 consecutive admissions to the hospital in a
      three-year period were reviewed. Chi square analyses and t tests were used to
      compare various groups of HIV-related admissions and non-HIV-related admissions
      on sociodemographic characteristics, length of stay, history of psychiatric
      hospitalization, and other clinical measures. RESULTS: One-hundred and sixty
      three admissions (7.8 percent of the total admissions) were judged to be HIV
      related. The largest category of HIV-related admissions, nearly half, were
      patients experiencing functional or psychological complications of HIV infection
      or risk. AIDS-phobic patients, who expressed irrational concerns about infection,
      accounted for 20.2 percent, and patients with organic manifestations for 18.4
      percent. If the AIDS-phobic, HIV-bereaved, and factitious HIV-positive admissions
      were excluded, the rate of HIV-related admissions was 5.2 percent. CONCLUSIONS:
      Psychiatric hospitals can expect a significant but not overwhelming number of HIV
      related admissions.

PMID- 7712248
TI  - Rates of sexually transmitted diseases among patients in a psychiatric emergency
      service.
AB  - OBJECTIVE: This study sought to estimate the prevalence of non-HIV sexually
      transmitted diseases among patients admitted to a psychiatric emergency service
      and to identify characteristics that might place members of this population at
      increased risk of acquiring these diseases. METHODS: Hospital medical records and
      records of public health departments' venereal disease control sections were
      retrospectively reviewed to determine if patients consecutively admitted to a
      psychiatric emergency service at a large urban public hospital had been tested
      for syphilis, gonorrhea, trichomonas, chlamydia, or herpes simplex in the 12
      months before admission and whether the tests were positive. Data on patients'
      demographic and clinical characteristics were also collected. RESULTS: Of 426
      consecutive patients studied, 214 (50.2 percent) were tested for one or more non
      HIV sexually transmitted diseases. Forty of those patients (18.7 percent) had
      positive tests. The rates of syphilis and gonorrhea among the patients were
      significantly higher than those estimated for the city and state where the study
      was done and significantly higher than the national estimate. Patients whose
      tests were positive did not differ significantly from those with negative tests
      in presenting psychiatric symptoms or diagnosis. CONCLUSIONS: An alarmingly high
      rate of non-HIV sexually transmitted diseases was found among patients treated in
      a psychiatric emergency service. However, no particular clinical subpopulations
      at increased risk for acquisition of these diseases could be identified.

PMID- 7712249
TI  - Effect of demographic and behavioral variables on burden of caregivers of chronic
      mentally ill persons.
AB  - OBJECTIVE: Persons who provide care for individuals with chronic mental illness
      experience both objective burden (observable, tangible cost) and subjective
      (perceived) burden. This study sought to determine the relative power of
      behaviors of chronic mentally ill clients, behaviors required of caregivers, and
      demographic characteristics of both groups in predicting burden. METHODS: A total
      of 189 caregiver-client dyads were studied using a cross-sectional, correlational
      design. Caregivers were interviewed by phone about clients' needs for help in
      nine areas and about seven potentially troublesome client behaviors. Correlation
      and regression analyses were used to determine relationships among variables.
      RESULTS: Caregivers reported much less subjective than objective burden, although
      the relationship between the two types of burden was not consistent across the
      various areas in which clients needed help. Overall, more of the reported burden
      was related to caregivers' behaviors (their day-to-day tasks) than to clients'
      behaviors. Burden was greatly increased for caregivers who lived with the client.
      Caregivers most at risk for burden were those who lived with male clients who
      threatened suicide. CONCLUSIONS: Caregivers become accustomed to the stabilized
      behavioral profile of the client. Mental health professionals should be sensitive
      to profiles and situations that may produce increased objective and subjective
      caregiver burden.

PMID- 7712250
TI  - Consumer perceptions of pressure and force in psychiatric treatments.
AB  - OBJECTIVE: Mental health consumers with serious mental illness were surveyed to
      obtain information about their experiences with and attitudes toward forced
      psychiatric treatment. METHODS: A 61-item survey questionnaire developed by the
      authors was administered by consumer volunteers to 105 persons with serious
      mental illness who were attending seven rehabilitation centers in Maryland. The
      questionnaire covered consumers' experiences and attitudes in three areas of
      forced treatment: medication, outpatient therapy or rehabilitation, and
      hospitalization. RESULTS: At some time during the course of their illness, 57
      percent of the respondents reported having been pressured or forced into
      hospitalization. In the year before the survey, 30 percent reported being
      pressured or forced into taking medication and 26 percent into attending a
      therapy or rehabilitation program. The most common type of pressure or force was
      verbal persuasion. Generally, respondents reported negative effects from forced
      treatment, although the intensity of the negative effects varied by treatment
      area, and about half retrospectively felt that the forced treatment was in their
      best interest. Many respondents believed that pressure or force has an
      appropriate role in psychiatric treatment, although most wished to maintain the
      right to refuse treatment that they considered not in their best interest.
      CONCLUSIONS: Differences in patterns of response to pressure and force in the
      three treatment areas highlight the variety of consumer experiences and the need
      to know more about the role of forced or pressured treatment in their lives.

PMID- 7712251
TI  - Comorbidity of dissociative disorders among patients with substance use
      disorders.
AB  - OBJECTIVES: The study replicated methods used in an earlier study to determine
      the prevalence of dissociative disorders among patients with substance use
      disorders and to examine demographic characteristics and history of childhood
      abuse among patients with and without dissociative comorbidity. METHODS: A total
      of 100 inpatients who were completing a substance abuse treatment program at a VA
      medical center were interviewed using the Dissociative Disorders Interview
      Schedule, which diagnoses dissociative disorders. Two additional screening
      measures of dissociative symptoms were used, as well as an instrument to measure
      IQ. RESULTS: Fifteen percent of the sample were diagnosed as having a
      dissociative disorder. Compared with patients without a dissociative disorder,
      the patients with a dissociative disorder had significantly higher median scores
      on the two screening measures, indicating more dissociative experiences and the
      presence of five distinct symptom clusters. The two groups did not differ in
      history of childhood abuse or IQ. CONCLUSIONS: The results support earlier
      findings suggesting that patients with substance abuse disorder should be
      routinely screened for dissociative symptoms and disorders.

PMID- 7712252
TI  - Medical services use by patients before and after detoxification from
      benzodiazepine dependence.
AB  - OBJECTIVE: The authors examined use of medical and mental health services before
      and after detoxification among a group of patients detoxified from
      benzodiazepines to see if the data suggested a reduction in service use and costs
      after detoxification, the so-called offset effect observed for treatment of
      alcohol and mental disorders. METHODS: Through a medical record review,
      information was collected about medical service use for patients aged 40 and
      older who were detoxified from benzodiazepines at Scott and White Clinic and
      Hospital between 1987 and 1991. RESULTS: Among the 76 patients, medical and
      mental health outpatient visits fell from an average rate of 25.4 visits per year
      before detoxification to 4.4 per year after detoxification. For the 44 patients
      with at least one inpatient stay besides the admission for detoxification, the
      mean number of inpatient days remained constant at three days per year before and
      after detoxification. CONCLUSIONS: Although a retrospective record review suffers
      from a range of limitations, the findings suggest that detoxification from
      benzodiazepines may be effective in reducing use of outpatient medical and mental
      health services and presumably in reducing costs of care.

PMID- 7712253
TI  - False allegations of sexual misconduct: clinical and institutional
      considerations.
AB  - That some therapists engage in sexual misconduct with patients has been
      unequivocally established. In recent years, however, some patients' allegations
      of sexual misconduct have been determined to be false. This paper describes four
      cases in which hospitalized psychiatric patients made false allegations. Such
      allegations may result from patients' seeking to gain monetarily or in other ways
      or from a desire for retaliation or revenge against a clinician who they believe
      has scorned, abandoned, or otherwise mistreated them. In other cases, especially
      among patients with a history of severe trauma, a patient's psychopathology may
      be inadvertently stimulated by diagnostic, treatment, or milieu activities. The
      authors recommend specific institutional responses to allegations of sexual
      misconduct, such as forming a clinical investigative team, conducting a physical
      examination, and reporting the charge to outside agencies or investigators when
      appropriate. Because false claims can have disastrous effects on all involved,
      clinicians should understand the presentations of such claims and the motivations
      behind them, and institutions should carefully develop a set of procedures for
      responding to them.

PMID- 7712254
TI  - Effect of nonviolent self-defense training on male psychiatric staff members'
      aggression and fear.
AB  - OBJECTIVE: Male staff members at two state psychiatric hospitals were trained in
      nonviolent self-defense skills for dealing with potentially assaultive patients
      to determine whether such training could reduce the number of assaults and
      episodes of patient restraint. METHODS: Three groups of male staff received
      didactic training, didactic and physical skills training, or no training in the
      nonviolent self-defense skills of protective profile, repel, and push-off, as
      well as in evasive movement. Effects of the training were evaluated using the
      Buss-Durkee Hostility-Guilt Inventory; a questionnaire about clinical experience
      and sports training; judges' evaluations of physical skill, aggression, and fear;
      a self-report questionnaire about the value of nonaggressive responses and felt
      fear and aggression; and a follow-up questionnaire about posttraining assaults.
      RESULTS AND CONCLUSIONS: Behaviorally expressed fear and aggression were
      significantly reduced among staff who received both didactic and physical skills
      training. The other two groups showed no significant changes in this area. During
      the two weeks after training, subjects trained in physical and didactic skills
      were involved in 23 percent fewer assaults than those who received only didactic
      training and 20 percent fewer assaults than those who received no training. The
      development of increased skill in nonviolent physical techniques of self-defense
      was strongly correlated with an increase in the value placed on the use of the
      skills and on nonviolent outcomes.

PMID- 7712255
TI  - Methods of assessing mental health consumers' preferences for housing and support
      services.
AB  - The authors reviewed 21 studies assessing housing preferences of mental health
      consumers to examine current methods of assessment, to obtain information on the
      reliability and validity of the assessment instruments used, and to determine
      whether a better approach to assessing preferences might be found. The review
      found little data on the reliability or validity of the assessment instruments
      and revealed heavy reliance on the use of fixed-choice questions that limit
      consumer expression of preferences. Responses to such questions can be misleading
      because they may or may not reflect real-life constraints, such as preferring a
      roommate only because living alone is not affordable. However, the authors
      believe the factorial survey model, which uses vignettes to present different
      combinations and characteristics of living arrangements, may allow investigators
      to better understand consumers' true preferences. They propose creating and pilot
      testing an instrument using such vignettes.

PMID- 7712256
TI  - The eye of the beholder: housing preferences of inpatients and their treatment
      teams.
AB  - The authors surveyed 80 hospitalized patients with serious mental illness and the
      patients' treatment teams to compare their perspectives about appropriate housing
      and support services following hospital discharge. The results showed that the
      opinions of patients and treatment teams differed markedly on housing preferences
      but converged on many basic service needs. Patients preferred more independent
      living arrangements, while treatment teams favored more structured environments.
      The authors believe that these conflicting views must be reconciled if patient
      preferences are to be reflected in discharge planning.

PMID- 7712257
TI  - Differences in social class among psychotic patients at inpatient admission.
AB  - A cross-sectional assessment of differences in social class and other
      sociodemographic variables at hospital admission for patients with psychotic
      disorders was carried out through a systematic survey of psychotic patients
      admitted to greater Baltimore psychiatric facilities between 1983 and 1989.
      Female patients, first-admission patients, and patients with bipolar disorder or
      other, nonschizophrenic psychosis were more likely to have been admitted to
      community, university, and private hospitals than to state hospitals. Patients in
      medium and higher social class categories were 1.29 to 2.57 times more likely to
      be admitted to community, university, and private hospitals than to state
      hospitals.

PMID- 7712258
TI  - Delivering comprehensive services to homeless mentally ill offenders.
AB  - A consortium of social services agencies developed a comprehensive community
      mental health services program for homeless mentally ill offenders in Portland,
      Oregon. Residential services were provided in a single-room-occupancy hotel.
      Forty-seven clients were accepted for the program, 38 actually entered the
      program, and 14 graduated--that is, attained sobriety and were placed in
      community housing. Problems complicating program implementation included
      differing philosophical approaches of key agencies, staff turnover, and financial
      shortfalls. Many potential clients were not accepted into the program because of
      recent violence or potential violence; some clients were expelled or
      reincarcerated because of violent behavior.

PMID- 7712259
TI  - Treatment refusal by an elderly man suffering intensely from treatment-resistant
      depression.
AB  - The authors consider the ethical issues involved in a case in which an elderly
      man suffering from recurrent, treatment-resistant depression expressed a wish to
      forgo life-sustaining treatment should it become necessary. The patient had no
      immediate life-threatening medical conditions but was in danger of becoming
      malnourished and dehydrated. The authors conclude that unrelieved suffering
      resulting from depression, when combined with repeated treatment failures, may
      justify refusal of life-sustaining treatment in very rare cases.

PMID- 7712260
TI  - Preparing for practice in an era of managed competition.
AB  - Psychiatrists must take steps to prepare for health reform that includes managed
      competition. They should focus on managed mental health care in their reading,
      reevaluate fundamental beliefs and values to encompass an understanding of
      managed care, and try to view managed care organizations as allies. Psychiatrists
      should also use practice guidelines, participate in quality improvement
      activities and outcome studies, and improve their relationships with health care
      managers and administrators.

PMID- 7712261
TI  - Colonial family care.

PMID- 7712262
TI  - Depression screening.

PMID- 7712263
TI  - Clozapine in aggression.

PMID- 7712264
TI  - National surveys find higher use of marijuana by students, more heroin-related
      hospital visits.

PMID- 7712265
TI  - Regional meeting abstracts. American Federation for Clinical Research.

PMID- 7712267
TI  - Stress and mental health in neonatal intensive care units.
AB  - The views of 34 neonatologists (a 78% response rate) and 192 neonatal intensive
      care nurses (a 66% response rate) were obtained on work, stress, and
      relationships in neonatal intensive care units. The survey was conducted by post
      and included Goldberg's General Health Questionnaire (GHQ). A comparison of the
      responses of neonatologists and nurses to 21 identical statements showed
      significant differences in 12. Most neonatologists felt that they involved nurses
      in critical patient care decisions, provided adequate pain relief for their
      patients, gave nurses adequate information on patients' progress after discharge,
      and were aware of little doctor-nurse conflict. However, the nurses' responses
      differed significantly in these areas, suggesting that the neonatologists may
      have a more rosy view of life in the neonatal intensive care unit than their
      nurse colleagues. Twenty seven per cent of neonatologists and 32% of nurses had
      GHQ scores indicating psychological dysfunction. The neonatologists who had
      dysfunctional scores differed from their colleagues in only one area surveyed--a
      higher proportion experienced conflict between the demands of their work and
      their personal lives.

PMID- 7712268
TI  - Pitfalls in respiratory monitoring of premature infants during kangaroo care.
AB  - The reliability of respiratory monitoring, using either chest or back electrodes,
      was studied in 13 preterm infants during kangaroo care (infant-parent skin to
      skin contact). In three out of four infants with chest electrodes both infant and
      parental respiration were clearly visible on pneumograms. In these infants
      apnoeic pauses were not registered because parental respiration was recorded as
      infant breathing. Bradycardia and oxygen saturation were, however, properly
      registered. In infants with electrodes placed on the back infant respiration was
      less superimposed by parental breathing. However, even in some of these infants
      parental respiration was visible in the pneumograms. It is concluded that during
      kangaroo care the electrodes should be placed on the back and monitoring should
      always include heart rate and oxygen saturation.

PMID- 7712266
TI  - Presence of secretory IgA antibodies to an enteric bacterial pathogen in human
      milk and saliva.
AB  - The concept of a common mucosal immune system in man was tested by examining the
      concurrent presence of specific-secretory IgA (SIgA) antibodies in human milk and
      saliva from three groups of subjects: 64 Sri Lankan women living in Sri Lanka; 20
      immigrant Asian women living in Birmingham (median duration of residence in the
      United Kingdom five years); and 75 Caucasian women living in Birmingham
      (controls). Enzyme linked immunosorbent assays (ELISA) were developed to detect
      enterotoxigenic Escherichia coli (ETEC) colonisation factor/1 (CFA/1) specific
      SIgA antibodies in milk and saliva. ETEC CFA/1 specific SIgA antibody activity
      was detectable in milk (37.5% and 25%) and saliva (42.1% and 35%) of Sri Lankan
      and immigrant Asian women, respectively, but not in any of the Caucasian
      controls. Eighty five point two per cent of subjects who were positive had
      specific antibodies detectable in both milk and saliva; 5% of all Sri Lankan
      women and 10% of all immigrant Asian women had detectable antibody only in
      saliva. These observations lend further strong support to the idea that a common
      mucosal immune system exists in man. The continuing presence of specific SIgA
      antibodies in Asian immigrants to previously encountered antigens suggests that
      there may be an 'immunological memory' in the human secretory immune system.

PMID- 7712270
TI  - Changes in oxygenation and heart rate after administration of artificial
      surfactant (ALEC) to preterm infants.
AB  - To determine if changes in oxygenation and heart rate occur after surfactant,
      changes in these variables were recorded continuously for 15 minutes before,
      during, and 15 minutes after the administration of the artificial surfactant ALEC
      to 21 preterm infants ventilated for respiratory distress syndrome. Median
      (range) birth weight and gestation were 1199 (561-2680) g and 28 (21-43) weeks,
      respectively. The mean (SD) time taken for administration was 17.6 (3.8) seconds.
      No clinically important changes resulted from the administration of ALEC in the
      mean (SD) values for oxygen saturation (before 91.3 (3.4)%, during 90.7 (3.2)%,
      after 90.4 (3.7)% and heart rate (before 143 (15), during 138 (17), after 142
      (16)). The maximum change in mean arterial oxygen saturation (SaO2) was a fall of
      4.8%.

PMID- 7712269
TI  - Congenital pneumonia due to Mycoplasma pneumoniae.
AB  - A case of probable vertical transmission of Mycoplasma pneumoniae is presented.
      The presence of M pneumoniae was demonstrated by the polymerase chain reaction
      (PCR) in the nasopharyngeal aspirate of a newborn who developed pneumonia shortly
      after birth. This result was confirmed by performing a second PCR, amplifying
      another part of the genome of M pneumoniae. It is concluded that M pneumoniae can
      be added to the long list of pathogens known to cause congenital pneumonia.

PMID- 7712271
TI  - Neonatal chest drain insertion--an animal model.
AB  - Trainees rarely see a neonatal pneumothorax because of the combination of
      decreased doctors' hours, the use of surfactant, and modern ventilator
      techniques. An animal model, using a dead rabbit, is described that could be used
      to train doctors and others in the management of this serious complication of
      neonatal care.

PMID- 7712272
TI  - Guidance after twin and singleton neonatal death.
AB  - A study was made to determine whether parents whose newborn twin (n = 72) had
      died differed from bereaved singleton parents (n = 70) concerning their
      satisfaction with professional guidance and care. Most parents felt supported by
      hospital staff, but the twin parents had fewer avenues of available support,
      especially after their baby's death. The twin parents' situation requires special
      attention because they have specific needs that are not always addressed by the
      current range of available support services.

PMID- 7712273
TI  - The pharmacology of inhaled nitric oxide.

PMID- 7712274
TI  - Treatment of newborn infants with inhaled nitric oxide.

PMID- 7712275
TI  - Intestinal dilatation in the fetus.

PMID- 7712277
TI  - Dr George Engelmann of St Louis (1847-1903) and the ethnology of childbirth.

PMID- 7712276
TI  - Hypertension in pregnancy.

PMID- 7712278
TI  - CRIB, son of Apgar, brother to APACHE.

PMID- 7712279
TI  - Chest position and pulmonary deposition of surfactant in surfactant depleted
      rabbits.
AB  - AIMS: To investigate the correlation between chest position and the distribution
      of surfactant in the lungs of surfactant depleted rabbits, to corroborate current
      guidelines on the intratracheal instillation of exogenous surfactant in newborns.
      METHODS: Twelve tracheotomised rabbits, depleted of pulmonary surfactant by
      saline bronchoalveolar lavage, were given intratracheal 99m Technetium labelled
      Exosurf in three positions (prone, right side down, and left side down) (n = 4 in
      each group). They were monitored for 10 minutes using dynamic gamma scintigraphy
      monitoring. Instillation completed, the lateral lying animals were turned to the
      opposite side to determine whether redistribution of the surfactant had taken
      place. The amount of radiolabelled surfactant deposited at the peripheral,
      central, dorsal and ventral parts of the lungs was then estimated by gamma
      counting of the lung sections at necropsy. RESULTS: Both gamma scintigraphy and
      gamma counting showed similar rates and total amount of surfactant accumulation
      in both lungs of the prone animals. In the lateral lying animals surfactant
      accumulated at a significantly faster rate in the dependent lungs: the amount of
      surfactant deposition was three to 14-fold that in the raised lungs (p = 0.017;
      nested ANOVA). Changing the chest position immediately after instillation did not
      redistribute the surfactant. In all three groups of animals there was no
      significant difference in deposition between the peripheral, central, ventral and
      dorsal parts of the lungs. CONCLUSIONS: Pulmonary distribution of intratracheally
      instilled surfactant is largely determined by gravity, and changing the chest
      position after instillation does not result in any redistribution of the
      surfactant. During the instillation of exogenous surfactant to newborn infants,
      keeping the chest in the horizontal position may therefore result in the most
      even distribution of the surfactant in the two lungs. Further deposition studies
      are required to evaluate the validity of the current recommendations on
      surfactant administration.

PMID- 7712280
TI  - Increase in interleukin-8 and soluble intercellular adhesion molecule-1 in
      bronchoalveolar lavage fluid from premature infants who develop chronic lung
      disease.
AB  - Interleukin-8 (IL-8), soluble intercellular adhesion molecule-1 (sICAM), elastase
      and neutrophils were assessed in bronchoalveolar lavage fluid from nine infants
      who developed chronic lung disease (CLD) after respiratory distress syndrome
      (RDS), seven who had recovered from RDS, and in four control infants. IL-8,
      sICAM, elastase and neutrophils in bronchoalveolar lavage fluid were increased in
      the CLD group, the differences being most pronounced at 10 days of age. When
      babies with and without CLD were compared at 10 days of age, bronchoalveolar
      lavage fluid from the babies with CLD had significantly increased IL-8 (114.0 vs
      12.7 ng/ml), sICAM (19.0 vs 1.1 micrograms/ml), elastase (6.9 vs 0.9
      micrograms/ml) and neutrophils (1.9 vs 0.4 x 10(9)/l). In serum the increased
      concentration of IL-8 observed at birth in the CLD (247 pg/ml) and RDS (192
      pg/ml) groups decreased over three weeks to the concentrations observed in the
      controls (< 70 pg/ml). Persistent inflammation could be a major contributory
      factor in the development of CLD.

PMID- 7712282
TI  - Parallel beta-domains: a new fold in protein structures.
AB  - A new type of structural domain, composed of parallel beta-strands folded into a
      coiled structure, has been observed in several protein structures within the past
      year. An analysis of the basic motif indicates that there are two distinct types,
      with variations likely to be discovered in the future.

PMID- 7712281
TI  - Low risk of seizure recurrence after early withdrawal of antiepileptic treatment
      in the neonatal period.
AB  - The risk of seizure recurrence within the first year of life was evaluated in
      infants with neonatal seizures diagnosed with a combination of clinical signs,
      amplitude-integrated electroencephalogram (EEG) monitoring, and standard EEG.
      Fifty eight of 283 (4.5%) neonates in tertiary level neonatal intensive care had
      seizures. The mortality in the infants with neonatal seizures was 36.2%. In 31
      surviving infants antiepileptic treatment was discontinued after one to 65 days
      (median 4.5 days). Three infants received no antiepileptic treatment, two
      continued with prophylactic antiepileptic treatment. Seizure recurrence was
      present in only three cases (8.3%)--one infant receiving prophylaxis, one treated
      for 65 days, and in one infant treated for six days. Owing to the small number of
      infants with seizure recurrence, no clinical features could be specifically
      related to an increased risk of subsequent seizures. When administering
      antiepileptic treatment, one aim was to abolish both clinical and
      electrographical seizures. Another goal was to minimise the duration of treatment
      and to keep the treatment as short as possible. It is suggested that treating
      neonatal seizures in this way may not only reduce the risk of subsequent seizure
      recurrence, but may also minimise unnecessary non-specific prophylactic treatment
      for epilepsy.

PMID- 7712283
TI  - 'Holy' proteins. I: Ribonuclease inhibitor.
AB  - The X-ray structure of the ribonuclease inhibitor from porcine pancreas shows a
      remarkable non-globular fold. It possesses a large central hole that forms part
      of the RNase A binding site.

PMID- 7712284
TI  - 'Holy' proteins. II: The soluble lytic transglycosylase.
AB  - Enzymes involved in the metabolism of the bacterial cell wall peptidoglycan are
      excellent targets for antibiotics. Penicillins and related beta-lactam
      antibiotics inhibit the enzymes that act on the peptide cross-links of the
      peptidoglycan. The X-ray structure of the transglycosylase revealed a two-layered
      ring of alpha-helices in a right-handed superhelical arrangement with a separate
      catalytic domain on top, which resembles the fold of goose-type lysozyme. Three
      sequence motifs were found that characterize the catalytic and substrate-binding
      sites in the enzyme. These motifs are present in a broad family of muramidases
      and chitinases.

PMID- 7712285
TI  - Unraveling a bacterial hexose transport pathway.
AB  - Structural information about proteins involved in bacterial hexose transport
      mediated by the phosphoenolpyruvate:sugar phosphotransferase system is rapidly
      accumulating. Within the past year, two crystal structures and two solution NMR
      structures of the histidine-containing phosphocarrier protein have been reported,
      adding structural details to previous NMR and crystallographic work on this
      protein and on enzyme IIA. The crystal structure of the regulatory complex
      between the glucose enzyme IIA and glycerol kinase has been determined, and the
      association of the histidine-containing phosphocarrier protein and either the
      glucose enzyme IIA or the mannitol enzyme IIA have been studied by NMR. Proposals
      concerning the mechanism of phosphoryl transfer and the protein-protein
      interactions involved may now be tested more rigorously using these data.

PMID- 7712286
TI  - Coagulation factors and their inhibitors.
AB  - A comprehensive three-dimensional picture of the coagulation process is beginning
      to emerge. Crystallographic structure determinations of prothrombin, factor Xa,
      factor IXa, tissue factor and factor XIII represent important advances in our
      understanding of the coagulation cascade. Similarly, structures of antithrombin,
      tissue factor pathway inhibitor and thrombomodulin provide details of endogenous
      anticoagulatory mechanisms. NMR spectroscopy of multiple domains of coagulation
      proteins represents an important contribution to the analysis of flexibility and
      rigidity of modular proteins. Thrombin, as the prime candidate for antithrombotic
      drug design, continues to be an object of intense efforts in applied
      crystallography.

PMID- 7712287
TI  - Protein kinases.
AB  - The structures of four serine/threonine protein kinases have been determined
      recently. By comparing these structures with that of the cAMP-dependent protein
      kinase (cAPK), it is now possible to see how the activity of these regulatory
      enzymes is controlled. Low activity is maintained through the conformation of the
      phosphorylation lip, domain rotations, and binding of substrate analog inhibitors
      and autoinhibitory domains.

PMID- 7712289
TI  - Structures of two classes of MHC molecules elucidated: crucial differences and
      similarities.
AB  - New structures of MHC molecules have significantly improved our understanding of
      molecular recognition in cellular immunology. Highlights include the first
      structure of a class II MHC molecule, complexed with a viral peptide and with a
      bacterial superantigen. A structure of an MHC-like Fc receptor is expected soon.
      Interesting comparisons can now be made between the recognition properties of MHC
      and MHC-like proteins.

PMID- 7712288
TI  - Cell surface adhesion receptors.
AB  - Several new structural motifs found in cell surface adhesion receptors have been
      described in the past few years. Also, several two-domain structures of
      extracellular portions of cell surface proteins have been reported. Structural
      models for complexes between receptors and counter-receptors have been proposed.
      The first reports on carbohydrate conformation in intact glycoprotein domains
      have recently appeared. These new data are presented within a more general review
      of the field of cell adhesion receptors.

PMID- 7712290
TI  - Structure-based drug design.
AB  - There are now many successful examples of the design of new ligands based on
      knowledge of target protein structures. In most cases those ligands are
      unsuitable as drugs because of problems of toxicity, stability or
      bioavailability. The past twelve months have also seen the description of the
      structures of many proteins which are either known to be targets for existing
      drugs or have clear potential to be utilized in therapy.

PMID- 7712291
TI  - The structure and function of lipoxygenase.
AB  - Lipoxygenases are non-heme iron enzymes that catalyze the dioxygenation of
      polyunsaturated fatty acids, yielding hydroperoxides. The first crystal
      structures have recently been published, revealing an unusual iron site. There
      have also been substantial developments in the analysis of the kinetics of the
      reaction, including the observation of uniquely large primary deuterium isotope
      effects. Exploitation of these results should enable substantial progress in
      understanding what appears to be a complicated and fascinating chemical
      mechanism.

PMID- 7712292
TI  - Mechanisms of enzymatic glycoside hydrolysis.
AB  - The determination of a large number of three-dimensional structures of
      glycosidases, both free and in complex with ligands, has provided valuable new
      insights into glycosidase catalysis, especially when coupled with results from
      studies of specifically labelled glycosidases and kinetic analyses of point
      mutants.

PMID- 7712294
TI  - Highlights in haem biosynthesis.
AB  - The haem biosynthesis pathway continues to provide surprises, from the first
      enzyme, 5-aminolaevulinic acid synthase, the mRNA of which contains an iron
      responsive element, to the last, ferrochelatase, that contains an iron sulphur
      cluster. 5-Aminolaevulinate dehydratase from animals are zinc-dependent enzymes
      while those from plants require magnesium. The first X-ray structure of a haem
      synthesis enzyme, porphobilinogen deaminase, has not only yielded clues about the
      mechanism of tetrapyrrole assembly but has also provided insight into the
      molecular basis of the human disease acute intermittent porphyria. Evidence is
      growing to suggest that a previously unsuspected alternative haem pathway may
      exist.

PMID- 7712293
TI  - Domain movements in protein kinases.
AB  - Structural studies of the catalytic subunit of the cAMP-dependent protein kinase,
      both by crystallographic methods and in solution, reveal two conformations.
      Crystal structures of several other protein kinases have also been solved in the
      past year. With this combined information we can begin to define mobile domains
      and subdomains within the conserved catalytic core.

PMID- 7712295
TI  - The regulation of catalysis in ATP synthase.
AB  - ATP synthase is regulated so as to prevent futile hydrolysis of ATP when the
      transmembrane proton electrochemical gradient, delta mu H+, falls. Mitochondria
      and chloroplasts have different mechanisms for inhibition of ATP synthase: by
      binding an inhibitor protein, and by stabilization of the ADP-inhibited state by
      making an intramolecular disulphide bond, respectively. The recently determined
      structure of bovine F1-ATPase is locked in a conformation that probably
      represents the ADP-inhibited state of the enzyme.

PMID- 7712296
TI  - Cobalamin-dependent methionine synthase: the structure of a methylcobalamin
      binding fragment and implications for other B12-dependent enzymes.
AB  - Cobalamin-dependent methionine synthase is a large enzyme composed of
      structurally and functionally distinct regions. Recent studies have begun to
      define the roles of several regions of the protein. In particular, the structure
      of a 27 kDa cobalamin-binding fragment of the enzyme from Escherichia coli has
      been determined by X-ray crystallography, and has revealed the motifs and
      interactions responsible for recognition of the cofactor. The amino acid
      sequences of several adenosylcobalamin-dependent enzymes, the methylmalonyl
      coenzyme A mutases and glutamate mutases, show homology with the cobalamin
      binding region of methionine synthase and retain conserved residues that are
      determinants for the binding of the prosthetic group, suggesting that these
      mutases and methionine synthase share common three-dimensional structures.

PMID- 7712297
TI  - Bibliography of the current world literature.

PMID- 7712298
TI  - Catalysis and regulation.

PMID- 7712299
TI  - Gastric emptying and the symptoms of vection-induced nausea.
AB  - OBJECTIVES: To examine the hypothesis that nausea during vection arises directly
      from an underlying alteration in gastric motility. DESIGN: The simultaneous
      application of vection and assessment of gastric emptying of a liquid, non
      nutrient test meal allowed the examination of the interaction between changes in
      gastric motility and symptoms. METHODS: Studies were conducted in 14 volunteers.
      Vection was induced by seating the subject inside a rotating circular drum, which
      was painted with vertical black and white stripes. In the control study (n = 8)
      the drum was not rotated. Gastric emptying was measured by gamma scintigraphy of
      a radiolabelled isosmotic saline test meal. RESULTS: Vection induced upper
      abdominal sensations (epigastric awareness) in 10 subjects, eight of whom
      subsequently reported nausea; autonomic symptoms of sweating and pallor were
      experienced by 12 subjects. Two subjects remained completely asymptomatic during
      vection. None of the subjects experienced any sensations during the control
      study. Gastric emptying was significantly delayed during vection (P < 0.01).
      There was a highly significant correlation between gastric emptying and the
      intensity of nausea. However, examination of the gastric emptying profiles did
      not support any direct association between altered gastrointestinal motor
      activity and symptoms. Two subjects with slowing of gastric emptying exhibited no
      nausea or upper abdominal symptoms, while another two experienced nausea when the
      underlying rate of gastric emptying was similar to that of the control period.
      CONCLUSIONS: The delay in gastric emptying of a liquid test meal induced by
      vection appears to be a variable epiphenomenon of nausea. A cause and effect
      relationship between gastric emptying and nausea therefore appears unlikely.

PMID- 7712300
TI  - Antroduodenal manometry: 24-hour ambulatory monitoring versus short-term
      stationary manometry in patients with functional dyspepsia.
AB  - OBJECTIVES: To examine the interdigestive and postprandial antroduodenal motility
      patterns of patients with functional dyspepsia using prolonged ambulatory
      antroduodenal manometry and to compare these findings with conventional
      stationary manometry. METHODS: Prolonged ambulatory and short-term stationary
      antroduodenal manometry were performed in 10 patients with functional dyspepsia
      and in 10 healthy volunteers (controls). RESULTS: During stationary manometry
      only a few interdigestive motor complex (MMC) cycles were recorded. Using the
      ambulatory technique, fewer MMC cycles were observed in patients than in controls
      (2.2 +/- 0.63 and 4.1 +/- 0.54, respectively; P = 0.030). During phase II of the
      MMC, both techniques showed a higher antral motility index in patients (P = 0.017
      and P = 0.049 for stationary and ambulatory manometry, respectively). The
      postprandial antral motility index was similar for patients and controls using
      stationary manometry. With the ambulatory technique, the antral motility index 1
      1.5 h after breakfast was lower in patients than in controls (P = 0.020). Both
      techniques showed that the patients had a higher duodenal motility index after
      dinner and after breakfast (P < 0.05). Both techniques revealed more burst
      activity in patients than in controls (stationary: 10.7 versus 1.8% of the time;
      ambulatory: 1.7 versus 0.2% of the time; P = 0.004 and P = 0.051, respectively).
      Using a 10-min window period before the onset of symptoms, seven symptom episodes
      (33.3%) were found to be related to burst activity and retrograde or non
      propagated phase III activity. CONCLUSIONS: Ambulatory manometry is superior to
      stationary manometry for evaluating patients with functional dyspepsia, because
      patients can be studied for a prolonged period (allowing adequate evaluation of
      interdigestive abnormalities) and under physiological conditions. Prolonged
      monitoring also allows assessment of the relationship between symptoms and motor
      abnormalities.

PMID- 7712301
TI  - Efficacy of omeprazole combined with antibiotics for Helicobacter pylori
      eradication and duodenal ulcer recurrence.
AB  - OBJECTIVE: To establish the efficacy of omeprazole combined with two antibiotics
      for Helicobacter pylori eradication and duodenal ulcer relapse. PATIENTS: Thirty
      seven patients with endoscopically proven duodenal ulcer and H. pylori infection.
      METHODS: Treatment consisted of 20 mg omeprazole daily for 4 weeks with the
      addition, during the second and third weeks, of amoxycillin (1 g three times
      daily) and metronidazole (1 g daily) (group A) or placebo (group B). Endoscopy
      and biopsy to assess ulcer recurrence and H. pylori status were performed at
      entry to the study, after 4 weeks of therapy, and 1 and 6 months after treatment.
      RESULTS: Duodenal ulcers healed in all patients. H. pylori infection was
      eradicated in 15 (79%) out of 19 patients in group A and one (6%) out of 16
      patients in group B (P < 0.01). One patient in each of the groups was lost to
      follow-up after 6 weeks. During the 6 month follow-up period, duodenal ulcers
      recurred in three of the 16 patients with H. pylori eradication, compared with 16
      of the 19 patients with persistent H. pylori infection (19 versus 84%; P < 0.01).
      CONCLUSION: The combination of omeprazole with amoxycillin and metronidazole is
      effective in H. pylori eradication. This triple therapy, which eradicates H.
      pylori, also significantly reduced duodenal ulcer relapse.

PMID- 7712302
TI  - The adhesion of Helicobacter pylori extract to four mammalian cell lines.
AB  - OBJECTIVE: To study the adherence of acid-glycine extract (AGE) from Helicobacter
      pylori to four mammalian cell lines: KATO III, CCL17, CCL156 and Neuro-2A.
      DESIGN: In vitro assays to assess H. pylori adherence were based on the principle
      of the affinity of the bacterial antigens to mammalian cells in culture. Protein
      extracts from mammalian cells were either coated onto 96-well microtitre plates
      or electrophoretically resolved and blotted onto immobilon-P membranes. When the
      adhesive proteins derived from the AGE of H. pylori adhered to the mammalian cell
      proteins, these adhesive antigens were detected by rabbit anti-H. pylori AGE
      antibodies. METHODS: The adhesive proteins in H. pylori NCTC11637 AGE were
      detected by enzyme-linked immunosorbent assay (ELISA) and Western blot under non
      denaturing conditions. RESULTS: Adhesive proteins constitute 5% H. pylori AGE
      proteins. The adhesive proteins adhered more readily to mammalian cell extracts
      than to bovine serum albumin. Modified Western blot analysis showed their
      affinity to a number of mammalian proteins ranging in molecular weight from 40 to
      900 kDa, and in particular to the 140-230 kDa proteins. CONCLUSIONS: The two in
      vitro adherence assays used effectively demonstrated the adherence of H. pylori
      to different mammalian cell lines. The 5% adhesive proteins from H. pylori may
      play an essential role in infection and colonization by H. pylori. Furthermore,
      adhesive proteins have similar adherence properties to mammalian cell components
      and may play an important role in the pathogenesis of H. pylori infection.

PMID- 7712304
TI  - Faecal alpha 1-antitrypsin concentration in the diagnosis and management of
      patients with pouchitis.
AB  - OBJECTIVE: To investigate the role of faecal alpha 1-antitrypsin concentration in
      the diagnosis and management of patients with ileal pouch-anal anastomosis.
      DESIGN: Prospective study. METHODS: Fifty-two measurements of faecal alpha 1
      antitrypsin concentration were taken from 33 patients operated on for ulcerative
      colitis. RESULTS: Patients with active pouchitis (44.4 +/- 7.1 mg%) had a three
      fold higher mean faecal alpha 1-antitrypsin concentration than patients in
      remission (13.7 +/- 1.3 mg%; P < 0.0001), than patients who had never had
      pouchitis (14.4 +/- 2.3 mg%; P < 0.003) and than patients with incontinent
      ileostomies (12.7 +/- 1.3 mg%; P < 0.004). Faecal alpha 1-antitrypsin
      measurements were 80% sensitive and 97% specific for active pouchitis. A
      significant positive correlation between the pouchitis disease activity index and
      faecal protein loss was observed (r = 0.702; P < 0.0001). The correlations
      between protein loss and other parameters were weaker (protein loss versus
      clinical score, r = 0.309; versus endoscopic score, r = 0.583; and versus
      histologic score, r = 0.558). CONCLUSION: Faecal alpha 1-antitrypsin
      concentration is a good indicator of the degree of intestinal inflammation in
      pouchitis and may be useful as a quantitative index of disease activity in
      prospective studies.

PMID- 7712303
TI  - Sorbitol absorption in the healthy human small intestine is increased by the
      concomitant ingestion of glucose or lipids.
AB  - OBJECTIVE: To test the effect of the concomitant ingestion of glucose or lipids
      on sorbitol absorption in the human small intestine using the hydrogen breath
      test. METHOD: After an overnight fast, on four occasions separated by at least 1
      week 14 healthy volunteers randomly ingested 20 g sorbitol alone, 20 g sorbitol
      and 20 g glucose, 20 g sorbitol and 9 g lipids, and 10 g lactulose. Hydrogen
      concentration was measured in end-expiratory samples every 10 min for 3 h, and
      then every 30 min for 5 h. Sorbitol malabsorption was calculated from the ratio
      of the areas under the curve. RESULTS: The estimated rate of sorbitol
      malabsorption was 98 +/- 14% (mean +/- SEM) when sorbitol was ingested alone, and
      was significantly lower when ingested with glucose or lipids (68 +/- 10 and 70 +/
      7%, respectively; P < 0.05). Orocaecal transit times did not differ
      significantly between the different time periods. CONCLUSION: Sorbitol absorption
      in the human small intestine is increased by the concomitant ingestion of glucose
      or lipids.

PMID- 7712305
TI  - Extracellular matrix proteins in human bile and gallstones.
AB  - OBJECTIVE: To investigate the presence of extracellular matrix (ECM) proteins in
      human bile and gallstones and to determine whether they play a role in gallstone
      formation. METHODS: ECM components [procollagen-III-peptide (P-III-P), laminin,
      and hyaluronic acid] in bile from patients with (n = 22) and without (n = 6)
      gallstone disease were investigated by immunoassay. Bile, gallstones, and serum
      were assayed for extracellular matrix components in an additional 19 patients
      with gallstone disease and gallstones were analysed in a third set of 26
      patients. The expression of hyaluronic acid synthetase in bile duct and gall
      bladder epithelia was investigated by immunocytochemistry. RESULTS: Hyaluronic
      acid levels were significantly elevated in hepatic and gall bladder bile, but not
      in the serum of patients with compared with those without gallstone disease (137
      versus 81 micrograms/l, respectively; P < 0.05). No differences were found
      between hepatic and gall bladder bile. Procollagen-III-peptide and laminin were
      detected in the hepatic bile of patients in both groups. Laminin levels were
      higher in gall bladder bile than in serum in all patients and measurable amounts
      of hyaluronic acid were found in gallstones. The amount of hyaluronic acid was
      inversely correlated to the volume of the gallstone, i.e., the smallest
      gallstones contained the highest levels of hyaluronic acid. No procollagen-III
      peptide or laminin was found in the gallstones. Immunocytochemistry of the
      epithelial cells of bile duct and gall bladder mucosa stained strongly for
      hyaluronic acid synthetase. CONCLUSIONS: Hyaluronic acid as a progenitor of ECM
      can be detected in bile and is significantly elevated in patients with gallstone
      disease. Small gallstones contain more hyaluronic acid than large stones,
      suggesting that hyaluronic acid may play a role in gallstone formation,
      particularly since it is produced by the epithelial lining of bile ducts and is
      found in gall bladder mucosa.

PMID- 7712306
TI  - The effect of alcohol on acid secretion by the bovine gall bladder in vitro.
AB  - OBJECTIVES: To determine whether acid secretion by gall bladder mucosa is
      influenced by alcohol and whether hydrogen ion output is increased when the gall
      bladder is perfused with moderate concentrations of alcohol. METHODS: Fifty
      bovine gall bladders were studied. Twenty-five served as controls and 25 were
      perfused (in groups of five) with varying concentrations of alcohol (w/v): 0.05,
      0.1, 0.2, 0.5 and 1.0%. Acid output was measured over 1 h and the results
      expressed as the mean. RESULTS: There was no significant difference between acid
      production by control gall bladders and those perfused with 0.05% alcohol (24.30
      +/- 8.7 versus 18.95 x 8.41 nmol/h), but the acid output was significantly
      increased when the mucosa was exposed to 0.1 and 0.2% alcohol concentrations
      (50.28 +/- 10.2 and 29.34 +/- 9.1 nmol/h; P < 0.001 and P < 0.0004,
      respectively). Perfusion with alcohol concentrations of 0.5 and 1.0%,
      significantly inhibited mucosal acid output (2.60 +/- 2.0 and -1.70 +/- 1.2
      nmol/h; P < 0.0001 and P < 0.0001, respectively). CONCLUSION: This study shows
      that perfusion of bovine gall bladder mucosa in vitro with moderate
      concentrations of alcohol stimulates acid output. This observation is important
      for assessing the link between alcohol and the risk of gallstone formation.

PMID- 7712307
TI  - Hepatocellular carcinoma in alcoholic cirrhosis: is sex hormone imbalance a
      pathogenetic factor?
AB  - OBJECTIVE: A sex hormone imbalance has been reported in patients with
      hepatocellular carcinoma (HCC). We investigated the serum levels of eight sex
      hormones in patients with alcohol-related and non-alcohol-related cirrhosis and
      HCC. METHODS: Luteinizing hormone, follicle-stimulating hormone, estradiol,
      progesterone, testosterone, androstenedione, dehydroepiandrosterone and sex
      hormone binding globulin were assayed in 81 patients with cirrhosis (59 men, 22
      women) and 97 with HCC and cirrhosis (82 men, 15 women). Hepatitis B or hepatitis
      C virus infection was present in 58% of patients with cirrhosis and 69% of
      patients with HCC. Alcohol abuse was the aetiopathogenetic factor in the
      remaining patients. RESULTS: In men, mean testosterone levels were at the lower
      limit of the normal range for both patients with HCC and for controls with
      cirrhosis. Mean estradiol levels were increased both in patients with HCC and in
      those with cirrhosis, but patients with alcohol-related HCC had higher estradiol
      levels (P = 0.0002). An index of sex hormone imbalance, the estradiol to
      testosterone ratio (ETR), was calculated. The ETR was significantly higher in
      patients with alcohol-related HCC (P = 0.0002). Multiple regression analysis
      showed that the ETR correlated best with patients' diagnosis (P < 0.05). In
      women, the ETR was significantly lower in patients with HCC than in controls with
      cirrhosis. CONCLUSIONS: Men with alcohol-related HCC are characterized by an
      oestrogen and androgen imbalance and have a higher ETR than patients with other
      types of liver damage. Since sex hormones modulate hepatocellular proliferation,
      our data suggest that a sex hormone imbalance plays a role in
      hepatocarcinogenesis in patients with alcohol-related cirrhosis.

PMID- 7712308
TI  - Effects of ursodeoxycholic acid on serum liver enzymes in patients with hepatitis
      C virus-related chronic liver disease.
AB  - OBJECTIVE: To study the effect of ursodeoxycholic acid (UDCA) on serum liver
      enzyme levels [alanine aminotransferase (ALT) and gamma-glutamyl transferase
      (GGT)] in 101 patients with hepatitis C virus-related chronic liver disease.
      METHODS: Forty-nine patients were assigned to receive UDCA (450 mg/day) over a
      period of 6 months and 52 to receive no treatment. RESULTS: In the UDCA group,
      serum ALT and GGT levels significantly improved. ALT values decreased from pre
      treatment levels of 157.0 +/- 62.6 IU/l to 82.5 +/- 46.4 IU/l (P < 0.05), and GGT
      fell from 141.3 +/- 86.2 IU/l to 66.0 +/- 49.5 IU/l (P < 0.001). No significant
      change occurred in the mean ALT and GGT levels in the control group. CONCLUSION:
      Although our encouraging preliminary results must be validated by double-blind
      histological trials, UDCA may be an alternative treatment for patients who fail
      to respond to interferon therapy.

PMID- 7712310
TI  - Novel drug therapies in inflammatory bowel disease.
AB  - This paper reviews the published data on novel drug treatments for inflammatory
      bowel disease. Steroids that are topically active or rapidly metabolized have a
      definite therapeutic role and have fewer long-term side-effects than other
      steroids. Methotrexate can promote remission in approximately 50% of patients,
      but is less effective in maintaining remission. Cyclosporin is valuable for
      treating patients with severe ulcerative colitis but is less valuable for
      patients with Crohn's disease. None of the drugs that modify specific
      inflammatory mediators have proven efficacy but tumour necrosing factor and CD4
      antibodies may be promising. In patients with distal colitis, lignocaine appears
      to be effective.

PMID- 7712311
TI  - Hypokalaemic rhabdomyolysis: an unusual presentation of coeliac disease.
AB  - OBJECTIVE: To describe the clinical presentation and management of a patient with
      hypokalaemic rhabdomyolysis secondary to coeliac disease. DESIGN: Retrospective
      study. SETTING: Hospital based. PATIENT: A 60-year-old Caucasian man presenting
      with weakness caused by hypokalaemic rhabdomyolysis secondary to coeliac disease.
      INTERVENTIONS: Following the diagnosis by jejunal biopsy, the patient was treated
      with both intravenous and oral potassium supplements, and a gluten-free diet.
      OUTCOME MEASURES: Resolution of weakness and restitution of normal villous
      architecture following treatment. RESULTS: The patient's myopathy responded to
      the potassium supplements, his diarrhoea and histological changes resolved while
      on the gluten-free diet. CONCLUSION: Patients with coeliac disease may present
      with hypokalaemia in association with steatorrhoea. If potassium loss is rapid,
      rhabdomyolysis may occur. Coeliac disease should be considered a cause of
      malabsorption-induced hypokalaemic rhabdomyolysis.

PMID- 7712309
TI  - Interferon-alpha can be used successfully in patients with hepatitis C virus
      positive chronic hepatitis who have a psychiatric illness.
AB  - OBJECTIVE: To determine whether individuals with concurrent active psychiatric
      disease and chronic hepatitis C virus (HCV) can be treated safely and effectively
      with interferon-alpha. DESIGN: Prospective, open label study. SETTING: Tertiary
      referral hospital. PATIENTS: Thirty-one consecutive patients with co-existent
      chronic HCV and a psychiatric illness. INTERVENTIONS: Interferon-alpha was
      administered at doses of either 5 MU three times per week for 6 months (n = 17)
      or 5 MU daily for 6 months (n = 14). METHODS: HCV-RNA in serum was measured using
      reverse transcriptase polymerase chain reaction. Serum alanine aminotransferase
      levels were assessed and liver biopsy was performed before and after 6 months of
      treatment and again after 6 months of follow-up. RESULTS: Twenty-nine of the 31
      patients completed 6 months of therapy. Two patients discontinued therapy after 2
      and 3 months of treatment. Serum alanine aminotransferase levels returned to
      normal in 22 (71%) patients. Fifteen (48%) of the 31 patients cleared HCV-RNA
      from their serum. Only four patients experienced a worsening of their psychiatric
      illness during treatment. Interferon therapy was discontinued in two of these
      patients. CONCLUSIONS: Patients with a co-existent psychiatric illness and
      chronic HCV can be treated successfully with interferon-alpha with the active
      participation of a psychiatrist and the maintenance of psychotropic drug therapy
      during interferon treatment.

PMID- 7712312
TI  - Favourable prognosis following variceal haemorrhage complicating hepatic
      sarcoidosis.
AB  - OBJECTIVE: To report the case of a patient with bleeding oesophageal varices due
      to portal hypertension complicating hepatic sarcoidosis. PATIENT: A 43-year-old
      man. METHODS: Six subsequent bleeds over 12 years were treated with
      sclerotherapy. RESULTS: Following sclerotherapy the patient has remained
      asymptomatic. CONCLUSION: Portal hypertension due to sarcoid liver disease can
      have a favourable prognosis and early referral for port-systemic shunting may be
      inadvisable.

PMID- 7712313
TI  - Early gastric cancer in a patient with Menetrier's disease, lymphocytic gastritis
      and Helicobacter pylori.
AB  - OBJECTIVE: To describe a patient with early gastric cancer, Menetrier's disease,
      lymphocytic gastritis and Helicobacter pylori infection. DESIGN: A single patient
      case report. PATIENT: A 73-year-old man presenting with lower limb deep venous
      thrombosis was found to have a gastric adenocarcinoma on upper gastrointestinal
      endoscopy. He subsequently had a total gastrectomy. RESULTS: Histological
      examination of the resected stomach showed an early gastric cancer and changes
      typical of Menetrier's disease, lymphocytic gastritis and Helicobacter-associated
      chronic gastritis. CONCLUSION: This case suggests a link between gastric
      adenocarcinoma, Menetrier's disease and lymphocytic gastritis. The presence of H.
      pylori is postulated as a possible aetiology.

PMID- 7712315
TI  - Abstracts from society meetings, 1994-1995.

PMID- 7712316
TI  - The 17th Annual Conference on Shock. Big Sky, Montana, June 5-8, 1994. Abstracts.

PMID- 7712314
TI  - Effects of nitric oxide on antral motility and gastric emptying in humans.
AB  - OBJECTIVE: It has been suggested that nitric oxide is a nonadrenergic
      noncholinergic (NANC) inhibitory neurotransmitter released by the nerves in the
      gastrointestinal tract. We studied the influence of nitric oxide on gastric
      emptying and antral motility using glyceryl trinitrate (GTN), a donor of nitric
      oxide and L-arginine as the substrate of nitric oxide synthase. DESIGN: Six male
      volunteers (aged 21-24 years) participated in this placebo-controlled, double
      blind study. METHODS: We investigated the effects of 0.8 mg sublingual GTN, 300
      mg/kg/h intravenous L-arginine or placebo on meal-stimulated antral motility and
      gastric emptying on four separate occasions. After an overnight fast, a 500 ml
      standard liquid meal was ingested and the gastric emptying rate assessed by
      ultrasound. The changes in antral cross-sectional areas were measured by
      ultrasonography and the antral motor activity was determined simultaneously using
      a multilumen perfused catheter. Blood samples were taken from fasted and fed
      patients before and after the administration of GTN, L-arginine or placebo to
      determine plasma glucagon and somatostatin levels. RESULTS: GTN at a sublingual
      dose of 0.8 mg and 300 mg/kg/h intravenous L-arginine significantly (P < 0.01)
      prolonged gastric emptying half-time, averaging 56 +/- 12 and 38 +/- 8 min,
      respectively, compared with the placebo control value (28 +/- 7 min). The antral
      motor activity, calculated as the motility index (number of contractions x
      mmHg/min) significantly decreased in both test series, i.e., after GTN from 375.5
      +/- 185.1 (control) to 104.4 +/- 55.7 (P < 0.01) and after L-arginine from 401 +/
      76 (control) to 285 +/- 57 (P < 0.05). L-arginine given intravenously at a dose
      of 300 mg/kg/h significantly increased plasma glucagon and somatostatin in fasted
      patients and increased postprandially released glucagon without affecting
      postprandial plasma somatostatin levels. GTN did not affect plasma hormone
      levels. CONCLUSIONS: Our results indicate that (1) exogenous nitric oxide
      inhibits gastric emptying and antral motor activity, which could be useful in the
      treatment of patients with functional disturbances of gastric motility and
      emptying; and (2) the reduction in gastric emptying and antral motility observed
      after the administration of L-arginine results from changes in plasma
      enterohormone release rather than from the enhanced formation of endogenous
      nitric oxide.

PMID- 7712317
TI  - The 6th Congress of the European Shock Society, Stockholm, Sweden, September 16
      17, 1994 and satellite symposium of the 7th European Congress on Critical Care
      Medicine, Innsbruck, Austria, June 18, 1994. Abstracts.

PMID- 7712319
TI  - Light and electron microscopy of the human hepato-duodenal ligament: a morpho
      functional study.
AB  - The morpho-functional relationships between the hepato-duodenal ligament and the
      superior part of the duodenum are analysed. Twenty-four specimens were removed
      during necropsies of adults and prepared according to various mesoscopic,
      microscopic, and ultramicroscopical methods, i.e., whole-mounts, membrane
      preparations, thick and thin histological sections, and polarized light,
      scanning, and transmission electron microscopy were employed. The hepato-duodenal
      ligament is formed by longitudinally elongated, type I collagen fiber bundles
      which are interlinked by more delicate bundles of type III collagen fibers.
      Longitudinally disposed elastic fibers are the principal component of the elastic
      fiber system of the ligament. These are in continuity with the elaunin and
      oxytalan fibers which are intermingled with the muscle cells of the vessels and
      duodenal wall, and fat cells of the ligament. Part of the muscle bundles of the
      external, longitudinal, muscle layer of the duodenum is anchored in the
      adventitial and subserosal collagen and elastic fiber framework of the organ
      while part inserts directly into the fibrous framework of the ligament. The
      fibrous system of the ligament is continuous with that of the subserosa and
      adventitia of the duodenum.

PMID- 7712318
TI  - Institutional and patient criteria for heart-lung transplantation.
AB  - Heart-lung transplantation is a complex, expensive, and resource-intensive
      procedure. It is performed more often where there is coexistence of end-stage
      pulmonary disease with advanced cardiac disease that is not secondary to
      pulmonary hypertension (e.g., some forms of congenital heart disease, some
      situations with Eisenmenger's syndrome, and possibly the coexistence of end-stage
      heart and end-stage lung disease). Available data indicate that some disease
      states are associated with a higher probability of successful outcome after HLT
      than are others. Objectively validated and reliable patient selection criteria
      cannot be obtained from the current medical literature. Expert opinion provided
      to OHTA contained varying degrees of detail and uniformity with respect to
      patient selection (Tables 11 and 12). While most agree that "irreversible
      cardiopulmonary disease" is an indication for this procedure, there are no
      published data that have provided details as to how patients so designated were
      selected as candidates for HLT. For example, for chronic obstructive pulmonary
      disease (emphysema), neither expert opinion nor published studies of HLT provided
      data indicating the stage of the disease at which a decision to transplant is
      reasonable and objectively justifiable. A similar lack of detail for cystic
      fibrosis, bronchiectasis, pulmonary fibrosis, sarcoidosis, asbestosis, and other
      diseases was noted. Thus, there are insufficient data regarding transplant
      recipients to permit the development of objective criteria for a threshold for
      HLT in the various disease states. The circumstances are more problematic
      regarding suggested contraindications for HLT. While objective survival rates
      obtained from registry data indicated that survival bore little relationship to
      recipient age, various opinions provided to OHTA specified a maximum age for HLT
      candidates, ranging from under 45 years to 60 years. Adverse factors and
      contraindications, such as "other significant disease," "recurrent pulmonary
      emboli," "hepatic disease," "infection," and "insulin-dependent diabetes" were
      nonspecific and unsupported by published, objective evidence. More ambiguous
      contraindications included "psychiatric illness," "poor family support
      structure," "history of noncompliance with medical regimens," and lack of
      "emotional stability." While psychiatric, psychologic, or sociologic evaluations
      of potential HLT recipients undeniably have relevance to patient selection, use
      of such criteria should be supported at least by evidence of generally consistent
      application across the transplant community. Of note was the recommended
      requirement that the recipient possess "adequate financial resources," which
      implies that the benefits of HLT are not expected to be equitably provided to the
      public.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7712320
TI  - Surgical anatomy of the pudendal nerve and its clinical implications.
AB  - A study of the surgical anatomy of the pudendal nerve (PN) was performed in 13
      female and 7 male cadavers. The knowledge of the precise anatomy and anomalies of
      this important nerve would help in better localization of the nerve and its roots
      and branches for neurostimulation or for pudendal canal decompression in pudendal
      canal syndrome. Two routes were used in the dissection: gluteal and perineal. The
      PN was identified and its course was followed from its roots to its termination.
      The PN was composed of three roots derived from the 2nd, 3rd, and 4th anterior
      sacral rami (S 2,3,4). The roots received a contribution from S 1 in five
      cadavers and from S 5 in one. The three roots formed two cords. The first root
      continued as the upper cord while the second and third root fused together
      producing the lower cord. The PN was formed by union of the two cords a short
      distance proximal to the sacrospinous ligament, and then crossed the back of the
      ligament. In no specimen did the nerve cross the ischial spine. The inferior
      rectal nerve arose from the PN in the pudendal canal in 18 cadavers. In two cases
      it came out proximal to the canal; this would spare the two subjects the
      anorectal manifestations of the pudendal canal syndrome. As the PN crossed the
      back of the sacrospinous ligament, it gave origin to a branch that supplied the
      levator ani muscle. This branch was only found in male cadavers and we call it
      "accessory rectal nerve"; the levator ani muscle in such cadavers was doubly
      innervated on its perineal aspect.

PMID- 7712321
TI  - Hemicorporectomy.
AB  - Intractable decubitus ulcers and femoropelvic osteomyelitis are rare sequelae of
      paraplegia. Therapy for these conditions ranges from the simple to the complex,
      including wound debridement and care, alimentary and urinary tract diversion, hip
      disarticulation, and myofasciocutaneous rotational flaps. Should the condition be
      recalcitrant to these modalities the only curative therapy is hemicorporectomy. A
      28-year-old rendered paraplegic 3 years ago presented manifesting sepsis;
      marasmus; hip and knee flexion contractures; suppurative sacral and femoropelvic
      decubitus ulcers, exposed bone, and osteomyelitis; and fecal and urinary
      incontinence. Pre-operative nutritional supplementation, wound debridement and
      care, and psychological counselling were provided. Hemicorporectomy was
      performed, including colostomy, ureteroileal conduit, gastrostomy, and
      translumbar amputation. Several anatomical, physiological, and operative
      technical perspectives are emphasized: a two-staged approach may be preferable-
      at the first setting an intra-peritoneal exploratory celiotomy with alimentary
      and urinary tract diversion; and at the second setting an extra-peritoneal
      hemicorporectomy; preservation of abdominal wall musculature and fasciae to
      facilitate wound closure; sequential and bilateral ligation of the arteriae et
      venae iliaca communis; translumbar amputation between the fourth and fifth lumbar
      vertebrae; extirpation of the fourth lumbar processus spinosus vertebrarum;
      closure of the dura mater and translation of musculi sacrospinalis into the
      vertebral canal; avoidance of hypervolemia and hyperthermia; avoidance of wound
      pressure; testosterone replacement therapy for eunuchism; and physical and
      occupational rehabilitation including adaptation to a customized bucket
      prosthesis.

PMID- 7712322
TI  - Follow the royal road: the case for dissection.

PMID- 7712323
TI  - The case for prosection: comment on R.L.M. Newell's paper.

PMID- 7712324
TI  - Follow the radical road: comment on R.L.M. Newell's paper.

PMID- 7712325
TI  - Andreas Vesalius on the teeth: an annotated translation from De humani corporis
      fabrica. 1543.
AB  - An annotated translation into English of Chapter 11, Book One, "On the Teeth,
      Which Are Also Counted as Bones," from Andreas Vesalius' De humani corporis
      fabrica. The translation incorporates the text of both the 1543 and 1555
      editions, and verified citations of ancient sources. In this chapter, Vesalius
      corrects errors of Galen and demonstrates and describes for the first time the
      anatomy and function of the dental pulp cavity.

PMID- 7712326
TI  - Assessment of basic medical sciences in an integrated systems-based curriculum.
AB  - Basic medical sciences at Sultan Qaboos University (SQU) are taught in a systems
      based curriculum. During the development of the courses different formats have
      been used for the written examinations and also different types of questions.
      This paper compares students' performance in relation to examination format and
      to types of questions used. The formats were non-coordinated (NCAs), each
      discipline having a separate paper; coordinated (CAs), questions from various
      disciplines being given in the same paper but with separate sections for each
      discipline; and integrated assessments (IAs), questions being grouped under
      structure, function, and problem-based integrated long essays. The types of
      questions used were multiple choice (MCQs), short essays (SEQs), and structured
      integrated long essays (SILEQs). Students performed better in SEQs than in MCQs.
      Our analyses also show that SILEQs measure skills similar to those of MCQs and
      SEQs combined. Students performed best in NCAs. In CAs, students concentrated on
      those disciplines carrying most weight in the final grade. Currently we use IAs
      consisting of two parts: part I, comprising MCQs and SEQs, and part II,
      comprising SILEQs. To date, students are performing better in part II than in
      part I. We suggest that it is prudent to use different types of questions to
      measure students' knowledge and skills when IAs are used for systems-based
      courses.

PMID- 7712327
TI  - Superior laryngeal nerve block: an anatomical study.
AB  - Superior laryngeal nerve anaesthesia is frequently used to facilitate
      endotracheal intubation in the awake patient. We have modified the transcutaneous
      approach to this nerve block to employ a short bevel needle. This improves
      tactile perception in performing the procedure thus simplifying identification of
      the correct depth of injection. This study was designed to determine the
      anatomical basis of superior laryngeal nerve anaesthesia and to estimate the
      success rate using our modified technique. At autopsy, 20 cadavers had nerve
      block performed substituting 0.02% methylene blue for local anaesthetic.
      Dissection was then performed to identify the anatomical structures stained by
      the simulated local anaesthetic. Additional dissections were performed in
      formalin-fixed cadavers. We found that the dye was injected into the paraglottic
      space bounded laterally by the thyrohyoid membrane and thyroid cartilage,
      medially by the laryngeal submucosa, caudad by the conus elasticus, cephalad by
      the hyoid bone, and anteriorly and posteriorly by the anterior and posterior
      thyrohyoid ligaments, respectively. The internal laryngeal nerve, the sensory
      branch of the superior laryngeal nerve, passed through this compartment and was
      heavily stained with simulated local anaesthetic. Resistance to the passage of
      the short bevel needle was provided by the lateral glossoepiglottic fold, not the
      thyrohyoid membrane as we had expected. Of 40 injections, 39 were deemed
      successful for a success rate of 97.5%. We conclude that this is a simple and
      highly successful technique for performing superior laryngeal nerve anaesthesia.

PMID- 7712328
TI  - Use of duplex sonography to investigate the effect of active and passive movement
      at the ankle joint for promoting venous return.
AB  - Among the joint and muscle pumps that are hemodynamically active and, in
      particular, bring about venous return in the lower limb, the so-called ankle pump
      is of paramount importance. The basic anatomical relationship of the talocrural
      joint to the venous network around the ankle is reviewed. Duplex sonographic
      measurement of the rate of blood flow in the great saphenous vein at the
      saphenous opening, at rest and during active and passive movements at the ankle
      joint, shows that such movements have an important effect on the rate of flow
      through the adjacent veins. Passive movement of the foot relative to the leg was
      brought about by a newly developed apparatus that can be either pneumatically or
      electrically operated. The action of the ankle pump against venous stasis, the
      arthrogenic congestive syndrome, and chronic venous insufficiency has
      demonstrated the prophylactic importance of this physiological mechanism. It can,
      when necessary, be replaced by an appropriately designed apparatus.

PMID- 7712329
TI  - Complete recovery of mice from a pre-established tumor by direct intratumoral
      delivery of an adenovirus vector harboring the murine IL-2 gene.
AB  - Direct introduction of exogenous genes into pre-existent tumors could provide an
      effective therapeutic approach for treatment of localized tumors. In this report
      we show that direct intratumoral delivery in animals of a replication-deficient
      adenovirus vector harboring the murine interleukin (IL)-2 gene (AD-mIL2) causes
      complete disappearance of P815 murine mastocytoma tumors in up to 75% of cases.
      Histological analysis of treated tumors revealed the presence of several zones of
      necrosis and the infiltration of macrophages and T cells. Moreover, the
      successfully treated animals develop a long lasting state of immunity during
      which further challenges with the tumor cells are rejected. To our knowledge this
      is the first successful in vivo treatment of an established tumor using
      adenoviral gene therapy methods.

PMID- 7712330
TI  - Correction of ornithine-delta-aminotransferase deficiency in a Chinese hamster
      ovary cell line mediated by retrovirus gene transfer.
AB  - Gyrate atrophy (GA) of the choroid and retina is an autosomal recessive
      chorioretinal degeneration, caused by deficiency of the mitochondrial matrix
      enzyme ornithine-delta-aminotransferase (OAT). This deficiency results in the
      accumulation of ornithine in the body fluids and leads to hyperornithinemia.
      Although the clinical phenotype is largely confined to the eye, OAT deficiency is
      a systemic disorder. With the final goal of applying gene therapy to this human
      genetic disease, we have established an in vitro model to test the correction of
      OAT enzymatic deficiency in mammalian cells, using OAT recombinant retroviruses.
      We report the construction of several Moloney murine leukemia virus (MoMLV)-based
      recombinant retrovirus vectors, in which the human OAT cDNA was placed under the
      transcriptional control of the mouse phosphoglycerate kinase (PGK) promoter or
      under the enhancer-promoter regulatory element derived from the MoMLV long
      terminal repeat (LTR). The retrovirus constructs were packaged in the PG13-GALV
      cell line and used to transduce C9, an OAT deficient cell line derived from
      Chinese hamster ovary cells (CHO-K1). We show that the recombinant retrovirus
      transfers the human OAT (hOAT) gene into C9. Expression of the hOAT gene in the
      transduced C9 deficient cell line exceeded the OAT mRNA level and enzymatic
      activity of endogenous human fibroblasts.

PMID- 7712331
TI  - An improved system for packaging recombinant adeno-associated virus vectors
      capable of in vivo transduction.
AB  - Adeno-associated virus (AAV) vectors are potentially useful for gene therapy of a
      number of human diseases. However, the use of these vectors has been limited by
      the lack of stable vector-packaging cell lines. The difficulties in developing
      packaging cell lines relate to low levels of rep gene expression from the AAV-p5
      promoter, and to the propensity of Rep proteins to suppress continued growth of
      immortalized cell lines. We describe here two new techniques which allow these
      problems to be circumvented. First, we have demonstrated that expression of rep
      from the human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter
      results in a 10-fold improvement of packaging efficiency. Second, we have
      overcome the inefficiency of vector plasmid transfection by generating cell
      populations containing rescuable AAV recombinant genomes. These improvements
      yielded a net increase of 50-fold in the packaging efficiency of the AAVp5neo and
      AAVp5lacZ recombinant vectors. The AAVp5lacZ vector packaged with this method was
      administered systemically to recently weaned C57BL mice, and mediated efficient
      expression of the beta-galactosidase reporter gene in cells of the airway
      epithelium and spleen. This indicates the in vivo activity of these vector
      stocks, and their potential utility for gene therapy.

PMID- 7712332
TI  - 'Bystander killing' induces apoptosis and is inhibited by forskolin.
AB  - 'Bystander killing' is a term used to describe the broad cell death associated
      with the transduction of the herpes simplex virus thymidine kinase gene (HSV1-tk)
      and administration of nucleoside analogs and which extends the killing effect to
      adjacent cells not transduced with HSV1-tk ('bystander cells'). HSV1-tk negative
      cells can be killed by co-culture with HSV1-tk positive cells at a ratio as small
      as one HSV1-tk positive to 32 HSV1-tk negative cells (1:32). In this report,
      several aspects of bystander killing are characterized. First, the sensitivity to
      bystander killing is shown to differ among cell lines. Second, cell-to-cell
      contact, or at least proximity between cells, is demonstrated to be necessary for
      bystander killing. Third, forskolin is shown to inhibit bystander killing. We
      also show that bystander killing is not species specific. Finally, it is
      demonstrated that cell death induced by bystander killing is mediated via
      apoptosis.

PMID- 7712333
TI  - A carcinoembryonic antigen polynucleotide vaccine has in vivo antitumor activity.
AB  - We have constructed a plasmid DNA encoding the full-length cDNA for human
      carcinoembryonic antigen (CEA) driven by the cytomegalovirus early
      promoter/enhancer and demonstrated that this plasmid can function as a
      polynucleotide vaccine. The immune response elicited by the CEA polynucleotide
      vaccine is dose and schedule dependent. There appears to be a threshold dose of
      50 micrograms capable of inducing CEA-specific lymphoblastic transformation,
      lymphokine release, and antibody response. Doses of 10 micrograms were
      significantly less effective. When 50-micrograms doses are employed, thrice
      weekly or weekly vaccination schedules more reliably elicit CEA-specific immune
      responses by day 43 than does an every-3-weeks schedule. Furthermore the CEA
      polynucleotide vaccine can immunoprotect against challenge with syngeneic CEA
      transduced colon carcinoma cells as early as 3 weeks after the first vaccination.
      Studies are ongoing to demonstrate the ability of CEA polynucleotide vaccination
      to treat pre-existing syngeneic mouse colon and breast carcinomas expressing
      human CEA.

PMID- 7712334
TI  - Long-term rat survival after malignant brain tumor regression by retroviral gene
      therapy.
AB  - Total regression of malignant brain tumors was observed in Wistar rats after
      retrovirus-mediated gene therapy. Tumors were induced by inoculation of C6 rat
      glioblastoma cells to a specific location in the rat brain and the tumors that
      developed were visualized by magnetic resonance imaging (MR). Retroviral vectors
      were constructed from a defective murine retrovirus to which the thymidine kinase
      (tk 1) gene from herpes simplex was added (HSV1tk). The vectors produced
      therapeutic viruses upon their introduction into retrovirus packaging cells.
      Delivery of the producer cells to the tumor mass and subsequent antiherpetic
      treatment eradicated the tumors completely, as observed using MRI. Some of the
      treated animals have been followed for over 8 months and show no signs of
      recurrence.

PMID- 7712335
TI  - Ovarian tumour antigens as potential targets for immune gene therapy.
AB  - Major new developments in the understanding of the molecular mechanisms involved
      in immune recognition of self, and immune mediated rejection of foreign antigens,
      have resulted in the development of a variety of novel therapeutic strategies for
      the treatment of cancer. Cornerstones of the advances in this area have been the
      identification of tumour antigens and demonstration of immune recognition of
      neoplastic cells, most notably in malignant melanoma. There are now a number of
      clinical immune gene therapy trials in progress for the treatment of cancer by
      stimulating immune mediated rejection of malignant cells. Here we examine the
      evidence for immune recognition of ovarian tumour cells and the presence of
      putative ovarian tumour antigens as potential targets for immune gene therapy of
      ovarian carcinoma.

PMID- 7712336
TI  - High level expression and export of beta-glucuronidase from murine
      mucopolysaccharidosis VII cells corrected by a double-copy retrovirus vector.
AB  - Retrovirus vectors were constructed to transfer and express the cDNA of the human
      lysosomal acid hydrolase beta-glucuronidase (GUSB) under control of the human
      GUSB promoter. Expression of the transcription unit (minigene) was evaluated in a
      GUSB-negative cell line established from a mouse with the lysosomal storage
      disease mucopolysaccharidosis (MPS) type VII. A vector designed to transfer
      single copies of the minigene (N2H beta H) expressed normal levels of GUSB
      activity in the deficient cells. GUSB expression was increased to several times
      greater than normal by inserting the minigene into a double-copy vector (DCH beta
      H), which places one copy of the transcription unit upstream of the retrovirus
      promoter in both the 3' and 5' long terminal repeats (LTRs) of the integrated
      provirus. The specific activity of GUSB and a control normal lysosomal enzyme,
      alpha-galactosidase (GLA), were higher in normal and in vector-corrected cells
      from confluent cultures than in subconfluent dividing cells. The ratios of GUSB
      to GLA were similar at all phases of cell growth, but the level of GUSB
      expression from the double copy vector was several-fold higher than from the
      single copy vector. To determine if this effect was controlled by the GUSB
      promoter, a vector was constructed using the thymidine kinase (TK) promoter to
      drive the human GUSB cDNA (NTK beta H). The levels of GUSB in cells corrected
      with this vector exhibited the same cell density dependent pattern as when the
      GUSB promoter was used, indicating that the variation in enzymatic activity was
      not a function of the GUSB promoter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712337
TI  - Reduction of cyanide levels in cassava during sequential sundrying and solid
      state fermentation.
AB  - The cyanide levels were followed during protein enrichment of cassava by the
      fungus Aspergilus oryzae. The total cyanogen level decreased by 158 mg/kg dry
      weight to 54.2 mg/kg dry weight as a result of the whole process including
      fermentation. The cyanogenic glucoside level decreased by 88% during the
      fermentation process while acetone cyanohydrin was retained in the cassava. The
      prefermentation processing which involved crushing, sundrying and milling the
      cassava into flour, reduced the total cyanogen levels by 40%. The process
      resulted in considerable reduction in the cyanogenic content of the product.

PMID- 7712338
TI  - Serum cholesterol and triglyceride levels in weight reduction program dropouts.
AB  - Dropouts of a weight reduction program are not evaluated for the lasting effects
      of weight reduction. This study was an attempt to learn about the benefits of
      weight reduction received and sustained by the dropouts of the program. Ninety
      seven males and females dropping out of a dietary weight management program after
      16-18 weeks of treatment, and after 9-9.4kg weight loss and wishing to rejoin the
      program for a second time after at least 9 months' absence from it, were
      considered for the study. Their body weight, serum cholesterol, serum
      triglyceride, and blood sugar levels at the beginning of the second attempt, were
      compared with the respective values at the beginning of the first attempt. All
      patients had regained the weight lost during their first attempt when they
      reported for a second attempt. However, serum cholesterol and triglyceride values
      were 15% and 26% less for females, and 17% and 24% less for males, compared to
      their respective values on the first attempt, in the subgroup of patients with
      normal blood sugar levels. In the subgroup with above normal blood sugar levels,
      however, serum cholesterol and triglyceride values showed an increase by 12% and
      17% respectively, for females, and by 2% and 7% respectively, for males, compared
      to their baseline values on their first attempt. The mechanism responsible for
      this observation was not uncovered. However, the observation that even an
      incomplete attempt at weight reduction appears to contribute in maintaining lower
      levels of serum cholesterol and triglyceride of at least those with normal blood
      sugar levels, is useful in nutritional counseling for emphasizing the health
      benefits of the weight reduction.

PMID- 7712339
TI  - Application of a colorimetric method to the determination of the protein content
      of commercial foods, mixed human diets and nitrogen losses in infantile
      diarrhoea.
AB  - Recently we reported on the application of a method for protein determination
      which measures nitrogen in Kjeldahl digests colorimetrically. This procedure has
      the advantage of eliminating the distillation and titration steps of the Kjeldahl
      method and it is ideal for nutritional studies, since many samples can be run in
      a single day. Accordingly, the purpose of the present report was to extend the
      application of this method to the determination of the protein content of
      commercially available foods such as dairy products, dry cereals or cereal based
      products and legumes and also to evaluate this method in the determination of the
      protein content of the mixtures of cooked foods served during lunch at the
      cafeteria of the Universidad Simon Bolivar, Caracas. In both cases the results of
      the colorimetric nitrogen agreed very well with those obtained by the macro
      Kjeldahl, indicating that the colorimetric method may be used in monitoring the
      protein content of commercial foods and in evaluating the protein offered in
      institutional food services. Finally, to further demonstrate the value of this
      method in clinical trials, we used it to monitor the daily nitrogen intake and
      nitrogen losses in 43 male young children with acute diarrhoea, and 15 with
      persistent diarrhoea fed liquid formulae, and showed that protein digestibility
      and retention were higher in persistent than in acute diarrhoea. The severity of
      acute diarrhoea affected negatively (r = -0.62) the percentage of protein
      absorbed, whereas the protein absorbed (r = 0.70) and retained (r = 0.55)
      correlated positively with protein consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712340
TI  - Influence of processing and cooking of carrots in mixed meals on satiety, glucose
      and hormonal response.
AB  - The influence of processing and cooking on the metabolic response to carrots in
      mixed meals was explored in two consecutive harvest years. The contribution of
      dietary fibre (4.4 g 1989 and 6.6 g 1990) from carrots was chosen to be different
      in order to compare effects with varying doses. The meals, composed of carrots,
      creamed potatoes, meat balls, lingonberry jam, white bread and light beer, were
      served in the morning after an overnight fast to 10 healthy male volunteers.
      Carrots were investigated raw, processed (blanched and frozen) and variously
      cooked (thawed, boiled and microwaved). The amount of dietary fibre from the
      vegetable, and the content of energy, digestible carbohydrates, fat and protein
      were similar in the meals compared. Significantly lower glucose, insulin and C
      peptide responses and higher satiety scores were elicited with raw carrots than
      with microwaved ones, harvest year 1989. The next year, with a higher dietary
      fibre intake from carrots, there were significant effects of processing only on
      the glucose response. Plasma beta-carotene levels tended to be higher
      postprandially with raw carrots than with microwaved ones. Hence, ordinary
      processing and cooking of vegetables can affect the metabolic response to a mixed
      meal. However, the influence seems to be varying and of minor importance in
      ordinary meals. Increasing vegetable portions entailing a higher soluble fibre
      content and a higher viscosity could further reduce the influence of processing.

PMID- 7712341
TI  - Aluminium leaching from utensils--a kinetic study.
AB  - Aluminium leaching from low quality (Al-Pb alloy) and high quality (Al-Mn alloy)
      utensils by water has been studied under different conditions of pH, boiling time
      and NaF concentrations. High fluoride concentration and low pH were found to
      enhance the leaching of Al more from low quality utensils than from high quality
      utensils.

PMID- 7712342
TI  - Vitamin C in leaves and seed oil composition of the Amaranthus species.
AB  - The foliage of 62 specimens of Amaranthus belonging to 10 species of grain and
      four of vegetable type were analysed for vitamin C content. The overall range of
      vitamin C was from 69 (A. cruentus, AG-122) to 288 mg/100 g (A. hypochondriacus,
      Rasna) in the grain type and 62 (A. tricolor, Amar-peet) to 209 mg/100 g (A.
      tricolor, AV-101, exp) in the vegetable type (fresh weight). Variation of vitamin
      C with leaf position (age) was also studied. While the oil content in 110 lines
      of A. hypochondriacus varied from 4.4 to 13.2%, most of the specimens had
      promising oil composition with regard to unsaturated fatty acids.

PMID- 7712343
TI  - Phytate and zinc bioavailability.
AB  - This review discusses evidence from human studies on the effects of dietary
      phytate on zinc bioavailability. In vitro and animal experiments have implicated
      calcium as a potentiating factor because it reacts with phytate, and zinc binds
      to the precipitate. Magnesium also reacts similarly to calcium, but most studies
      have not considered this factor. Protein provides amino acids, some of which are
      able to desorb zinc from the precipitate and improve bioavailability. Some
      predictive ratios, derived from animal studies, have been directly applied to
      human studies. The studies reviewed included those on: zinc status of groups,
      apparent absorption of zinc in normal subjects and ileostomists, true absorption
      using a stable isotope, plasma tolerance, and the accumulation in the body of a
      radioisotope. It was concluded that detrimental effects of phytate could be
      demonstrated on zinc bioavailability, but that the studies had not been designed
      specifically to demonstrate whether the interactions found in animal studies also
      apply to humans. It is suggested that more targeted research is required before
      predictive ratios are used for humans.

PMID- 7712345
TI  - Caring for mother & baby. Moving on to solid foods.

PMID- 7712344
TI  - The adverse effects of long-term cassava (Manihot esculenta Crantz) consumption.
AB  - Cassava (Manihot esculenta Crantz) is an important dietary staple for more than
      500 million people in developing countries. People eat 60% of the cassava
      produced and one third of the harvest feeds animals. All cultivars of cassava
      contain the cyanogenic glucoside, linamarin, but in different concentrations. The
      roots of those cultivars with high cyanogenic content are processed to reduce the
      level of linamarin, because linamarin is hydrolysed in the intestinal tract of
      both men and animals by microbial flora and HCN is released. Researchers have
      implicated the sublethal levels of HCN produced on ingestion in the development
      of a number of metabolic diseases in both man and animals when cassava-based
      diets are consumed over a long period of time but the release of HCN cannot fully
      explain the metabolic effects of ingested linamarin. A significant amount of
      linamarin remains intact and is excreted in the urine. It appears that the intact
      linamarin inhibits Na+K+ATPase causing electrolyte imbalance within the cell.
      This phenomenon is exacerbated by free radicals generated by the hypoxia/normoxia
      cycles created by cyanide released from linamarin, which cause lipid peroxidation
      and cell membrane damage. When the supply of endogenous thiosulphate is adequate,
      cyanide plays a very minor role in the development of lesions. The amount of
      damage is related to the quantity of linamarin routinely ingested at sublethal
      levels. There appears to be species differences in the rate of the development of
      diseases and the intensity.

PMID- 7712346
TI  - Sex--a national taboo.

PMID- 7712347
TI  - Sir William Power Memorial Lecture 1994. Families in Britain: change and
      continuities.

PMID- 7712349
TI  - Ageing issues: pension-related matters.

PMID- 7712348
TI  - An inner urban funded maternity care programme. Maternity projects: teenage
      pregnancies.

PMID- 7712350
TI  - Does nature know best? Background and mechanisms of natural family planning.

PMID- 7712351
TI  - "Free speech" system breakdown.

PMID- 7712352
TI  - Anonymous HIV survey results.

PMID- 7712354
TI  - Medico-actuarial mortality investigation. The Association of Life Insurance
      Medical Directors and the Actuarial Society of America. 1913.

PMID- 7712353
TI  - Major gene influence on the propensity to store fat in trunk versus extremity
      depots: evidence from the Quebec Family Study.
AB  - Regional fat distribution is related to higher risks of cardiovascular morbidity
      and mortality, independent of general obesity. In particular, a centralized
      pattern of fat deposition, characterized by greater abdominal stores relative to
      extremity stores, is associated with a higher propensity to metabolic
      complications. Motivated by these considerations, we have initiated a systematic
      investigation of several measures of regional fat distribution aimed at the
      identification of possible major gene effects. Two measures approximate the size
      of subcutaneous fat stores: the sum of six skinfold thicknesses (SF6 = abdominal
      + suprailiac + subscapular + calf + triceps + biceps), and the sum of three trunk
      skinfold thicknesses (TSF3 = abdominal + suprailiac + subscapular). Both of these
      phenotypes are highly correlated with total fat mass, 0.83 and 0.78 for SF6 and
      TSF3, respectively. The trunk to extremity ratio [TER = TSF3/ (calf + triceps +
      biceps)] is perhaps the most important of these phenotypes insofar as it is an
      index of centralized obesity; it is modestly correlated with fat mass (r = 0.18).
      Each of these phenotypes was adjusted for total fat mass by regression prior to
      analysis so that we could examine genetic effects on these measures of regional
      fat distribution without the confounding influence of the determinants of fat
      mass itself. Segregation analysis of SF6 and TSF3 controlled for total fat mass
      suggests the presence of a major effect underlying the observed phenotypic
      distribution; however, tests on the transmission probabilities did not
      substantiate the segregation of a Mendelian gene.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7712355
TI  - Body build and longevity. 1927.

PMID- 7712356
TI  - Skeletal muscle metabolism and body fat content in men and women.
AB  - The purpose of the present study was to verify the relationships between
      indicators of body fat content and specific characteristics of skeletal muscle in
      a large sample of men and women. Six skinfold thicknesses (sigma 6S) and maximal
      oxygen uptake (VO2 max) were measured in 348 Caucasian subjects (149 women and
      199 men). Fiber type proportions (type I, type IIA, and type IIB) and activity
      levels of marker enzymes for the Krebs cycle (malate dehydrogenase, MDH) and for
      the fatty acid oxidation (3-hydroxyacyl CoA dehydrogenase, HADH) pathways were
      determined in vastus lateralis muscle samples. No significant correlation was
      found between fiber type proportions and sigma 6S. Significant and negative
      correlations were, however, obtained in both genders between the sigma 6S and MDH
      enzyme activity (r = -0.23; p < 0.01), but not between the sigma 6S and HADH
      enzyme activity. When individuals with low and high amount of subcutaneous fat
      but paired for VO2max were compared, vastus lateralis of fat men exhibited the
      same proportion of type I fiber (38.6 +/- 10.3 vs 38.5 +/- 13.4%) and HADH
      activity level (3.43 +/- 1.05 vs. 3.34 +/- 0.81 U/g), but had about 20% less MDH
      enzyme activity than vastus lateralis of leaner men (158 +/- 35 vs. 198 +/- 43
      U/g;p < 0.05). No difference was found in any of these muscle phenotypes when
      comparisons were made between women with low and high amount of subcutaneous fat
      but also paired for VO2max. Moreover, no relations were observed between skeletal
      muscle fiber type proportion or metabolic markers with relative subcutaneous fat
      distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712357
TI  - A role for testosterone in the maintenance of seasonally appropriate body mass
      but not in lipectomy-induced body fat compensation in Siberian hamsters.
AB  - The purpose of this study was to test whether serum testosterone (T)
      concentrations characteristic of reproductively active, long-day-housed Siberian
      hamsters are necessary for compensatory increases in nonexcised fat pads
      following removal of epididymal white adipose tissue (EWAT) and/or for the
      maintenance of seasonally appropriate body weights in these hamsters. Long-day
      housed hamsters were castrated or left intact, sham or EWAT lipectomized, and
      given T or cholesterol (C) implants. All groups had ad libitum food access except
      for two castrated T-treated groups that were pair-fed to their C-treated
      counterparts to control for effects of T on food intake. C-treated castrates had
      decreased body weights compared with all other groups, suggesting a role of T in
      the maintenance of seasonally appropriate body mass. Since the T-treated hamsters
      pair-fed to these T-deficient animals exhibited seasonally appropriate body
      weights and fat pad masses, T does not appear to affect these parameters through
      the modulation of food intake. All fat pads of C-treated animals were smaller
      than those of ad libitum- or pair-fed, T-treated castrates; however, EWAT was the
      only fat pad that was smaller in the C-treated sham-lipectomized group than in
      gonad-intact sham-lipectomized hamsters. This result may indicate an enhanced
      sensitivity of EWAT to T. The effects of T on fat pad mass were not associated
      with proportionate changes in lipoprotein lipase activity, suggesting that the
      major effect of T on fat accumulation occurs through other mechanisms in this
      species. C-treated lipectomized hamsters compensated for the body fat deficit 8
      weeks after lipectomy via statistically non-significant increases in
      retroperitoneal and inguinal WAT mass. This finding suggests that, whereas T is
      necessary for maintenance of seasonally-appropriate body weight, it is not
      necessary for fat pad compensation after EWAT lipectomy.

PMID- 7712358
TI  - Fibrinogen in obesity before and after weight reduction.
AB  - Several studies have shown that obesity is associated with atherosclerosis. The
      reason may be that there is often a gathering together of risk factors for
      cardiovascular disease in obesity. Recently plasma fibrinogen level has been
      identified as an important cardiovascular risk factor. The aim of the study was
      to investigate fibrinogen levels in obesity before and after weight reduction.
      Obese but otherwise healthy patients with overweight problems were studied. 448
      female patients (39.1 +/- 13.2 years, body mass index 38.7 kg/m2) and 136 male
      patients (39.4 +/- 12.8 years, body mass index 40.7 kg/m2) were examined after
      overnight fasting. Sixty patients (44 female, 16 male) were studied after 9.5 +/-
      6.2 month of dieting (1200 kcal/day: 20% protein, 30% fat and 50% carbohydrates).
      The weight loss was 16.7 +/- 11.0 kg in the female and 16.2 +/- 6.7 kg in the
      male patients, and blood pressure, triglycerides, blood glucose and uric acid had
      declined. The fibrinogen level correlated with the body mass index, the waist
      circumference, the hip circumference and the waist to hip ratio. The fibrinogen
      level also correlated with insulin. A partial correlation of fibrinogen and
      insulin continued to exist after removing the linear effects of the other
      variables measured. After weight reduction, the level of fibrinogen was lower. In
      patients with extreme overweight and high fibrinogen levels, who reduced their
      BMI by 7.4 +/- 1.24 kg/m2, the weight loss correlated with the decrease in
      fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712359
TI  - Assessing Impact of Weight on Quality of Life.
AB  - This paper is a preliminary report on the development of a new instrument, the
      Impact of Weight on Quality of Life (IWQOL) questionnaire, that assesses the
      effects of weight on various areas of life. We conducted two studies utilizing
      subjects in treatment for obesity at Duke University Diet and Fitness Center. The
      first study describes item development, assesses reliability, and compares pre-
      and post-treatment scores on the IWQOL. In the second study we examined the
      effects of body mass index (BMI), gender, and age on subjects' perceptions of
      impact of weight on quality of life. Results indicate adequate psychometric
      properties with test-retest reliabilities averaging .75 for single items, and .89
      for scales. Scale internal consistency averaged .87. Post-treatment scores
      differed significantly from pre-treatment scores on all scales, indicating that
      treatment produced positive changes in impact of weight on quality of life. The
      results of the second study indicate that the impact of weight generally worsened
      as the patients' size increased. However for women there was no association
      between BMI and impact of weight on Self-Esteem and Sexual Life. Even at the
      lowest BMI tertile studied, women reported that weight had a substantial impact
      in these areas. There were also significant gender differences, with women
      showing greater impact of weight on Self-Esteem and Sexual Life compared with
      men. The impact of age was a bit surprising, with some areas showing positive
      changes and others showing no change.

PMID- 7712360
TI  - The relationship between weight and psychological functioning among adolescent
      girls.
AB  - This study investigated whether Body Mass Index (BMI) was associated with various
      aspects of psychological functioning in a sample of largely Caucasian adolescent
      girls. Three hundred sixty-five adolescent girls ranging from ages 14 through 19
      were assessed for general psychological functioning utilizing the Symptom
      Checklist-90-Revised (SCL-90-R), and functioning specific to eating, shape and
      weight utilizing the Eating Disorders Inventory (EDI). Excess weight was
      associated with higher scores on the Bulimia, Body Dissatisfaction and Drive for
      Thinness subscales of the EDI. Excess weight was not, however, associated with
      general psychopathology or any of the subscales of the SCL-90-R. The results
      suggest that excess weight may carry risk for pathology specifically related to
      eating, shape and weight in adolescent girls, but not for general forms of
      psychopathology.

PMID- 7712361
TI  - Obesity level and attrition: support for patient-treatment matching in obesity
      treatment.
AB  - Obesity treatment studies report attrition rates from 20% to 45%. To reduce
      attrition, researchers have proposed matching patients to treatment based upon
      level of obesity. The current study attempted to validate the commonly held
      assumption that a mismatch between obesity level and treatment will promote
      attrition. The level of obesity and attrition rates of 39 adults who enrolled in
      a 12-session behavior therapy program were examined. As obesity level increased,
      so did attrition. Sixty-nine percent of subjects with mild obesity, 43% of
      subjects with moderate obesity and 0% of subjects with severe obesity completed
      treatment.

PMID- 7712362
TI  - Obesity research and medical journalism.

PMID- 7712363
TI  - Human body composition and the epidemiology of chronic disease.
AB  - Obesity and body fat distribution (FD) are established risk factors for chronic
      diseases. The body mass index (BMI) and the waist/hip circumference ratio (WHR)
      are used conventionally as indices of obesity and FD in epidemiological studies.
      Although some general limitations of these indices are recognized, others that
      affect their use in relative risks for disease are not well recognized. These
      include effects of sex, ethnicity, and especially age on the relationships
      between these indices and body composition, which can result in substantial
      misclassification of obesity and FD. There is considerable variability in body
      composition for any BMI, and some individuals with low BMIs have as much fat as
      those with high BMIs. This results in poor sensitivity for classifying levels of
      body fatness (e.g., too many "false negatives," or overweight individuals
      classified as not overweight), and relative risks are attenuated across all
      categories of BMI. A more serious problem, however, is that at different ages the
      same levels of BMI correspond to different amounts of fat and fat-free mass. Data
      from the Rosetta Study and the New Mexico Aging Process Study show that older
      adults have, on average, more fat than younger adults at any BMI, due to the loss
      of muscle mass with age. As a result, the sensitivity of BMI cutpoints with
      respect to body fatness decreases with age, and the use of a fixed cutpoint for
      all ages results in "differential misclassification bias." Taken together, these
      issues suggest that the increases with age in the prevalences of overweight and
      obesity, and in the risks for chronic diseases, may be mis-estimated using BMI.
      Similar issues may affect the use of WHR for estimating prevalences and
      associated risks of FD. New field methods for estimating body composition are
      available that can be applied in large, epidemiologic follow-up studies of
      chronic diseases. These methods will allow epidemiologists to consider, for
      example, whether it is increased fat, or the replacement of fat-free mass with
      fat, with age that is associated with risk for chronic disease.

PMID- 7712364
TI  - Body compartment and subcutaneous adipose tissue distribution--risk factor
      patterns in obese subjects.
AB  - The purpose of this study was to investigate whether upper body obesity and/or
      visceral obesity are related to cardiovascular risk factors among severely obese
      subjects, phenomena that have previously been reported in more heterogeneous body
      weight distributions. 2450 severely obese men and women aged 37 to 59 years, with
      a body mass index of 39 +/- 4.5 kg/m2 (mean +/- SD) were examined cross
      sectionally. Eight cardiovascular risk factors were studied in relation to the
      following body composition indicators: four trunk and three limb circumferences,
      along with weight, height and sagittal trunk diameter. From the latter three
      measurements lean body mass (LBM, i.e., the non-adipose tissue mass) and the
      masses of subcutaneous and visceral adipose tissue were estimated by using sex
      specific prediction equations previously calibrated by computed tomography. Two
      risk factor patterns could be distinguished: 1. One body compartment-risk factor
      pattern in which the subcutaneous adipose tissue (AT) mass and, in particular,
      the visceral AT mass were positively related to most risk factors while the lean
      body mass was negatively related to some risk factors. 2. One subcutaneous
      adipose tissue distribution- risk factor pattern in which the neck circumference
      was positively and the thigh circumference negatively related to several risk
      factors. It is concluded that lean body mass (LBM), visceral and subcutaneous
      adipose tissue masses as well as neck and thigh circumferences, used as indices
      of subcutaneous adipose tissue distribution, are independently related to
      cardiovascular risk factors in severely obese men and women.

PMID- 7712365
TI  - Life insurance and overweight.

PMID- 7712367
TI  - President's column: healthcare reform.

PMID- 7712366
TI  - Deinstitutionalization of chronically mentally ill patients.

PMID- 7712369
TI  - Regional addictions training centers opened across the country.

PMID- 7712368
TI  - Dual diagnosis: a model for intermediate care.
AB  - Dual diagnosis traditionally refers to both a psychoactive substance abuse
      disorder and mental illness co-existing in the same person. For this paper,
      mental illness will refer to those patients with a chronic major mental illness
      (i.e., major depression, manic depression, schizophrenia or schizoaffective
      illness).

PMID- 7712370
TI  - [A review of the past work of the Society of Plastic Surgery of Chinese Medical
      Association].

PMID- 7712371
TI  - [Anastomosis of small artery using ZT medical adhesive and soluble stent].
AB  - The conventional technique of interrupted suture in microvascular anastomosis is
      difficult to perform and timeconsuming. A new method with ZT medical adhesive and
      soluble intravascular stent is introduced. Using this method, end-to-end
      anastomosis of small arteries could be performed easily and quickly. Both the
      patency rate and histopathologic changes at the anastomosis sites were examined.
      In comparison with suture technique, similar patency rate was obtained.
      Inflammatory reaction in mid and outer layers of the vessel was observable and
      reendothelialization of the intima was identical.

PMID- 7712372
TI  - [Management of vessel defect in digit replantation].
AB  - Many severed digits are complicated with vessel defects and make replantation
      more difficult. Based on experimental study, we have repaired vessel defect in
      207 cases (261 digits) by 12 methods. 240 digits (92%) survived. Experimental and
      clinical procedure, treatment of choice and related problems are described.

PMID- 7712373
TI  - [Reconstruction of radiocarpal and humeroscapular joints with vascularized
      fibular head].

PMID- 7712375
TI  - [Experience in the use of "moist burn ointment"].

PMID- 7712374
TI  - [A comparison between "moist ointment" and 0.25% iodophor, silver sulfadiazine
      paste and 0.1% rivanol in the treatment of deep II degree burn wounds].
AB  - One hundred and fifteen patients suffering from deep II degree burn were randomly
      divided into four groups, and "Moist ointment," 0.25% iodophor, silver
      sulfadiazine paste and 0.1% rivanol were respectively used as topical agents.
      Their effects were observed and compared. The results showed that "Moist
      ointment" group was significantly inferior to other groups in respects of healing
      of wound surface, bacteriostatic property, cost of treatment and formation of
      hyperplastic scar. Therefore, we suggested that the use of moist ointment in the
      treatment of deep II degree burn wound should be prohibited.

PMID- 7712376
TI  - [The observation and evaluation therapeutic effects of "moist ointment"].
AB  - From Mar. 1990 to Feb. 1993, a total of 23 patients with moderate or minor burn
      cases, who had been treated with "Moist ointment" before admission, were
      admitted. All the wounds were severely infected except one with scar deformity.
      17 cases were complicated by toxic symptoms. 7 cases were accompanied with
      septicemia and among them 3 cases died with in 48 hours after admission. The
      mortality was 13%. In 14 cases skin grafting was done. 15 cases had scar
      deformity in different sites. The incidence of scar formation was 65%. It is our
      opinion that "Moist ointment" is not a good method in the treatment of burn
      patients.

PMID- 7712377
TI  - ["Moist burn ointment" brought about multiple systemic complications in children
      with burns].
AB  - From January 1990 to December 1992, twenty-one burned children, who were treated
      with "Moist burn ointment", were transferred to our hospital after the occurrence
      of invasive infection, multiple systemic complications or electrolyte disorder.
      The age ranged from 1 to 5 years. The total burn area ranged 5-30 per cent (mean
      16.0 +/- 5.8 per cent) of the body surface area. All patients exhibited
      complications of two or more systems and electrolytic disorder when they were
      admitted. Of the 21 patients, 4 died. We believed that the severe infection of
      burn wounds, resulted from the application of "Moist burn ointment" was the main
      factor of causing multiple organ damage. Therefore, it is suggested that the
      "Moist burn ointment" should be used with great caution.

PMID- 7712378
TI  - [Surgical treatment of orbital fracture].
AB  - In last six years, 51 cases (34 males, 17 females) of orbital deformities caused
      by fracture were treated. According to careful examinations, x-ray and CT scan,
      the operation plan was made. The coronal incision or plus lower eyelid incision
      were employed. Subperiosteal dissection began from the upper margin of the orbit
      to release input soft tissue and reposition the eyeball. Rib bone was grafted for
      orbital defects. Canthoplasty was used if necessary. The surgical results were
      satisfactory.

PMID- 7712379
TI  - [Experimental study of tissue reaction produced by indigenous small-sized silicon
      gel breast prosthesis].

PMID- 7712380
TI  - [Correction of severe epicanthus using the square-flap method].
AB  - The square-flap method has been adopted gradually in plastic surgery because of
      lengthening effectively the distance between two points on the skin surface. Good
      results have been obtained in the treatment of severe epicanthus in 14 cases of
      26 eyes by using modified square flap since 1990. This paper describes the
      operation design, advantages and key points of the surgery.

PMID- 7712381
TI  - [The application of subdermal vascular network skin flap of neck-shoulder-humerus
      to repair large skin defects of the face and neck].
AB  - The subdermal vascular network skin flap of neck-shoulder-humerus (SVN flap) has
      been used to repair large defects of the face and neck in 33 cases in last ten
      years. The greatest flap was 9 cm x 27 cm. Clinical applications showed that SVN
      flap had many advantages including big size, thinness and high viability.

PMID- 7712382
TI  - [Subcutaneous injection of fatty tissue pearls--experimental study and clinical
      applications].
AB  - In 20 female adult rats, fatty tissue of 0.6 or 1.2 g was taken from each side of
      the pelvis. One fatty block, after being cut into pearls of about 2 mm in
      diameter, was injected subcutaneously to the left side of the back while another
      was transplanted en bloc in the right side. The rats were randomized into four
      groups and samples of fat were taken at 3, 6, 12 and 24 weeks. After 24 weeks,
      the sample from left side was found to be 21.1% of its original weight while the
      right side was only 6.9% (P < 0.05). In clinical practice, subcutaneous fat was
      sucked out from submandibular or abdominal regions, cut into pearls of 2-3 mm in
      diameter and injected to depressed area, such as glabella or naso-labial grooves.
      The procedure was applied to 27 sites of 15 cases. Follow-up of 6 months showed
      satisfactory results in 51.9%, acceptable in 18.5% and no effect in 29.6%.

PMID- 7712383
TI  - [Block hydroxyapatite artificial bone in augmentation rhinoplasty: experimental
      study and clinical applications].
AB  - The lower dense block hydroxyapatite artificial bone (BHAB), a new material for
      augmentation rhinoplasty, having the characteristic of easy to be carved and
      contoured, was used in 18 New Zealand white rabbits. The results demonstrated
      BHAB had good biocompatibility and well maintained the augmented contour.
      Satisfactory effects were gained in 13 clinical applications.

PMID- 7712384
TI  - [Laboratory research of biomechanics assay of skin wound healing].
AB  - The study described skin wound healing process in mice in the field of
      biomechanics by assaying the wound breaking strength (WBS) at different time with
      the INSTRON 4300 Materials Tester (England). The result revealed there was no
      significant change of WBS on the 3rd and 4th days. From the 5th to 21st day the
      WBS increased rapidly. From the 21st to 28th day the increased of WBC became slow
      and after the 28th day WBS tended to be stable. By the day of seven, the healing
      wound strength was 14% of normal skin and by the day of 28 the strength was 80%.
      Histopathologic appearance manifested a gradual change process of wound from
      inflammation to fibril healing. By this we divided the wound healing process into
      three periods: adhesion period (1st to 4th day), fibril healing period (5th to
      28th day) and fibril reconstructive period (after the 28th day). The study
      provided a clinical reference for the best times of removing sutures and taking
      functional exercise after an operation.

PMID- 7712385
TI  - [Myocardial function after fluid resuscitation with addition of 1-6-FDP in
      severely burned rabbits].
AB  - An experimental study is designed for the evaluation of the effect of fluid
      resuscitation with addition of 1-6FDP on myocardiac function in severely burned
      rabbits. 60 rabbits were divided into four groups. Group A (n = 15) served as
      control without treatment. The animals in group B (n = 15) were treated with 1-6
      FDP immediately after burning. The animals in group C (n = 15) were treated with
      balanced saline solution (BSS). The animals in group D(n = 15) were treated with
      BSS plus 1-6-FDP. All rabbits sustained 25% TBSA full thickness burn. LVSP, LV +/
      dp/dt max and PV were measured before burn, immediately after burn, and 1, 3, 5,
      7 h, after burn, except that PV was not measured immediately after burn. The
      results showed that depression in myocardial contractility and relaxation were
      noted immediately after severe burn. Fluid resuscitation alone did not
      significantly improve myocardial function (P > 0.05 compared with control). The
      administration of 1-6-FDP showed a beneficial effect in improving myocardial
      contractility and relaxation within 3 hours postburn. With fluid resuscitation
      plus 1-6-FDP, myocardial contractility and relaxation were improved statistically
      significantly as compared with the control group (P < 0.01).

PMID- 7712386
TI  - [Changes in fat absorption and effect of early enteral feeding following burn
      injury].
AB  - In order to approach this problem, a new animal model was developed in this
      study. Results indicated that the intestinal ability of absorbing nutrients was
      not markedly attenuated, and the reduction of portal blood flow was the primary
      cause of decrement of absorption of nutrients after burn injury. Therefore it is
      proposed that a timely and effective restoration of the portal circulation might
      improve the absorption ability. From the results of our present study, it seems
      probable that early enteral feeding can significantly increase the portal blood
      flow.

PMID- 7712387
TI  - [The pharmacokinetics of ceftazidime in the burned patients].
AB  - Pharmacokinetic studies were carried out following systemic administration of
      ceftazidime in ten burn patients (TBSA 30%-60% and with full-thickness burn) and
      six healthy volunteers. Dynamic ceftazidime concentrations in blood, urine and
      blister fluid were analysed by HPLC. The results showed that the burned patients,
      especially during their shock phase, some pharmacokinetics parameters differed
      from that of normal volunteers, in that the volume of distribution (0.45 +/- 0.06
      L/kg vs. 0.23 +/- 0.05 L/kg) and non-renal clearance of drug (30.54 +/-
      21.97ml.min-1 vs. 11.08 +/- 4.91 ml.min-1) increased, but the elimination of half
      life was prolonged. The result indicated that it was not necessary to increase
      the dosage of ceftazidime in extensive burns in the early period. Burn blister
      fluid concentrations were higher than MIC. Ranging from 1.004-21.62
      micrograms/ml, indicating that systemic ceftazidime could penetrate second-degree
      burn tissue in the early postburn stage.

PMID- 7712388
TI  - [Injected fat grafting].

PMID- 7712389
TI  - [Advances in the research of the prevention and treatment of multiple organ
      failure].

PMID- 7712390
TI  - Summary of the national guidelines for the diagnosis and management of lipid
      disorders in Taiwan. The experts panel.
AB  - In Jan. 1994, The ROC Society of Internal Medicine and the International Lipid
      Information Bureau, Taiwan (ILIB, Taiwan) jointly announced national guidelines
      for the diagnosis and management of lipid disorders. This guideline review the
      scientific basis and strategies for coronary artery disease (CAD) prevention.
      This guidelines were developed by an experts panel with various scientific
      backgrounds. Both two recent publications, the International Task Force and
      European Atherosclerosis Society (EAS) in 1992 and Adult Treatment Panel II (ATP
      II) from the National (USA) Cholesterol Education Program (NCEP), were adopted
      and modified. This guideline covered basic metabolism of lipoprotein, detection
      method of lipoprotein analysis, coronary risk factors, managements of
      dyslipidemia, goal of therapy and local epidemiological data. In this guidelines,
      lipid disorders are classified into hypercholesterolemia (serum cholesterol > 200
      mg/dL), combined hyperlipidemia (serum cholesterol > 200 mg/dL and triglyceride >
      200 mg/dL) and hypertriglyceridemia (serum triglyceride > 200 mg/dL). In the
      absence of CAD and with less than two risk factors, target levels for LDL
      cholesterol should be < 160 mg/dL; with more than two risk factors, < 130 mg/dL;
      in the presence of CAD, 100 mg/dL. In individuals with hypertriglyceridemia the
      target levels for triglyceride are 200 mg/dL. Secondary prevention of CAD is
      considered as one of the most important issue. Two generalized modalities are
      recommended to achieve the goal, i.e., non-pharmacological therapy which include
      weight reduction, regular exercise, smoking cessation, life style modification
      and pharmacological therapy. It is hoped that this guideline could help medical
      personnels dealing with patients with dyslipidemia and eventually, reduce the
      occurrence of CAD in Taiwan.

PMID- 7712391
TI  - Hemostatic effects of heat probe thermocoagulation for patients with peptic ulcer
      bleeding: an experience of 329 patients.
AB  - BACKGROUND: The mortality rate of peptic ulcer bleeding has kept around 6-10%
      over the past thirty years. Rebleeding is the most important adverse prognostic
      factor. Heat probe thermocoagulation is suspected to have good hemostatic effect,
      there is doubt whether the experience of performing the HPT treatment for peptic
      ulcer bleeding will influence the hemostatic rate. So we report our experience of
      a large series for heat probe thermocoagulation. METHODS: Patients with an active
      bleeding source (spurting or oozing) or a nonbleeding visible vessel (NBVV) in a
      peptic ulcer disease were enrolled in this study. We used an Olympus GIF IT-10 or
      GIF 2T-10 panendoscope, an Olympus heat probe unit and a 3.2 mm probe (Olympus
      Co., Taipei, R.O.C.) to treat peptic ulcer bleeding. We classified the faculty
      into junior physician, having experience in less than 20 procedures, and senior
      physician, having experience in more than 20 procedures. RESULTS: Between
      September 1986 and October 1993, we treated 329 patients with active bleeding or
      nonbleeding visible vessels at the ulcer craters. The stigmata of recent
      hemorrhage in these patients included spurting hemorrhage in 102 cases (31%),
      oozing hemorrhage in 105 cases (31.9%), nonbleeding visible vessels in 122 cases
      (37.1%). The bleeders were most frequently found in the stomach (181,55%), then
      the duodenum (133,40.4%). The energy applied to each case was 886 +/- 844 joules
      (mean +/- SD). The initial hemostatic rate was 95.1% (313/329). Rebleeding
      occurred in 74 cases (23.6%), and 52 cases received a second heat probe
      thermocoagulation with to result in ultimate hemostasis in 43 cases (82.7%).
      Junior physician obtained similar initial hemostasis rate and rebleeding rate
      (92.6%, 26.4%) as compared with 96.2% and 22.7% of senior physician. Totally 33
      patients received emergency operation, and 5 patients died. The volume of total
      blood transfusion was 2830 +/- 2184 ml (mean +/- SD). The hospital stay was 7.4
      +/- 4.6 days (mean +/- SD). CONCLUSIONS: Heat probe thermocoagulation is very
      effective in the arrest of peptic ulcer bleeding with minimal complications and
      it is easy to learn in a short period of time.

PMID- 7712392
TI  - Treatment of porto-systemic encephalopathy with lactitol verus lactulose: a
      randomized controlled study.
AB  - BACKGROUND: Lactitol (beta-galactosido-sorbitol), a novel disaccharide analogue
      of lactulose, has been suggested as an alternative to lactulose in the treatment
      of portosystemic encephalopathy (PSE) in Western country. In order to assess its
      therapeutic effect and adverse reaction in PSE in the Chinese, we conducted this
      study. METHODS: Forty-one patients with PSE were enrolled in this study. Patients
      were randomly divided into 2 groups to receive lactitol (n = 21) or lactulose (n
      = 20) for 5 days. The doses of both drugs were adjusted to keep daily bowel
      movement of 2 to 3 times. The PSE index (mental state, EEG, asterixis, number
      connection test [NCT], and ammonia) was evaluated in each patient before and
      after treatment. Daily doses of lactitol and lactulose, stool frequency, and side
      effect were recorded. RESULTS: The mean dose of lactitol used was 66.3 +/- 36.4
      gm and that of lactulose was 56.9 +/- 32.1 ml of lactulose. The majority of
      patients (37/41) gained clear consciousness after 5 days' treatment. In the
      lactitol group, blood ammonia, EEG, NCT, asterixis, mental status and PSE index
      before treatment were 208 +/- 62 micrograms/ml, 2.9 +/- 0.8, 4.0 +/- 0.0, 2.7 +/-
      1.5, 2.9 +/- 0.7 and 77.1 +/- 10.5, respectively. All parameters decreased
      significantly after 5 days' treatment (119 +/- 50 micrograms/ml, 1.1 +/- 1.0, 2.9
      +/- 1.2, 1.7 +/- 1.1, 0.7 +/- 0.7, and 34.4 +/- 16.0, p < 0.05). The lactulose
      group had the similar results. However, the improvement of PSE index after
      therapy in the lactitol group was significantly higher than that in the lactulose
      group (42.7 +/- 19.3 vs 31.1 +/- 13.7, p < 0.05). In addition, more patients in
      the lactitol group than in the lactulose group (67% vs 20%, p = 0.003) favored
      the taste of their assigned drugs. No patient who received lactitol experienced
      any side effects; however, six patients treated with lactulose complained of
      meteorism and flatulence, and four complained of nausea. CONCLUSIONS: Both
      lactitol and lactulose are effective in the treatment of PSE, though the effect
      of lactitol seems slightly superior to that of lactulose in our study. Lactitol
      is more acceptable to our patients due to better palatability and less side
      effects. Lactitol is another good alternative in the treatment of PSE.

PMID- 7712393
TI  - Do immunosuppressants cause posttransplant diabetes mellitus?
AB  - BACKGROUND: Posttransplant diabetes mellitus (PTDM) was originally described by
      Starzl in 1964. The incidence is around 3-46%, according to several reports.
      Etiologies and risk factors of PTDM have been discussed after it was described
      and recognized as a complication of renal transplantation. METHODS: Twenty-five
      consecutive renal transplants in 24 recipients were reviewed, and 3 cases of
      posttransplant diabetes mellitus were found. Cyclosporine A (CsA), Azathioprine
      (Aza) dose and maintenance dose of Prednisolone (Pred.), rejection episodes,
      total dosage of steroid used at the time of acute rejection were carefully
      recorded and analyzed. RESULTS: The mean age of 3 living-related and 22 cadaveric
      transplant recipients was 32.7 +/- 7.5 and 33.5 +/- 6.8 years in PTDM and non
      PTDM patients, and the onset of PTDM was, on the average, 11.3 +/- 10.6 months.
      Comparative studies between non-PTDM and PTDM groups showed that age, rejection
      episodes, total dose of methylprednisolone used in acute rejection, CsA level,
      and dosage of CsA, Aza and prednisolone at 1,6,12 and 24 months were not
      significantly different from one another. CONCLUSIONS: No significant risk
      factors or definitive mechanism involved in the development of PTDM were
      identified in this study. It is suggested that immunosuppressants are involved in
      the occurrence of PTDM, and probably neither a single factor is responsible nor
      is dose dependency involved.

PMID- 7712394
TI  - Anastomotic leakage following pancreaticoduodenectomy.
AB  - BACKGROUND: Since Whipple's successful resection of the head of the pancreas and
      duodenum in 1935, pancreaticoduodenectomy has become a standard operation for
      periampullary malignancies. Although the operative mortality has decreased
      dramatically in the recent years, it continues to be associated with high
      morbidity; with anastomotic leakage remaining a major problem. METHODS: One
      hundred and seventy-six pancreaticoduodenectomies performed for periampullary
      lesions during the past 27 years were reviewed. These included 171 Whipple
      operations, 4 total pancreatectomies and 1 pylorus-preserving
      pancreaticoduodenectomy. Among them, 40 cases were complicated with anastomotic
      leakage following pancreaticoduodenectomy. Their management strategy and outcome
      were reevaluated. Furthermore, the factors suggested to affect
      pancreaticojejunostomy leakage were also analyzed. RESULTS: The overall operative
      mortality was 15.3%, which decreased to 6.7% in recent two years. However, a high
      complication rate of 50% remained. Among the complications of the whole series
      (46.6%), anastomotic leakage accounted for 22.7% (40/176). Leakage occurred in 28
      pancreaticojejunostomies (16.3%), 9 hepaticojejunostomies (5.1%) and 6
      gastrojejunostomies (3.4%). Twelve patients required reoperation for ongoing
      sepsis or bleeding. This experience disclosed that in most cases
      hepaticojejunostomy leakage (8/9) could be successfully managed without
      operation. While three of the six gastrojejunostomy leaks survived after
      conservative treatment, two of the remaining three patients operated died of
      sepsis. Among cases with pancreaticojejunostomy leakage, 12 survived after
      conservative treatment, whereas 6 died of sepsis. Among 10 operated patients,
      only 3 patients survived. Earlier reexploration for uncontrolled leakage,
      probably within the first eight postoperative days, seemed to be the only chance
      for life saving. As far as the risk factors of pancreaticojejunostomy leakage are
      concerned, there seemed to exert no significant influence in terms of
      intraoperative blood loss, type and sequence of anastomosis as well as pancreatic
      stenting. The only clue that may affect the surgical outcome is technical; more
      experienced (> or = 10 Whipple operations) surgeons tended to render less
      morbidity and mortality. CONCLUSIONS: The retrospective analysis of our
      experience in pancreaticoduodenectomy discloses a trend toward decreased
      mortality rates in the recent years but operative complications remain high.
      Among the possible complications, anastomotic leakage is still a troublesome
      concern. Although conservative treatment can benefit most patients, earlier
      reexploration for uncontrolled sepsis should be considered. If a good result is
      anticipated, this complicated procedure should only be performed by an
      experienced surgeon.

PMID- 7712395
TI  - Epidemiological study of head injuries in central Taiwan.
AB  - BACKGROUND: Head injury plays a major role in emergency neurosurgery and is the
      leading cause of neurosurgical mortality at Taichung Veterans General Hospital.
      Statistical data show that a similar condition exists in other teaching hospitals
      in the central Taiwan area, which includes more than one-quarter of the entire
      population and has more than one-third of the total land of Taiwan. A clinical
      statistical survey of head injuries in this area may provide a better
      understanding of the realistic situation in Taiwan. Reports on head injuries in
      Taipei City, Taipei area, and Hualian County are also cited for comparison.
      METHODS: The present study is based on a cooperative investigation of head
      injuries by 18 teaching hospitals in central Taiwan from July 1991 to June 1993.
      All patients received a neurological examination including the Glasgow coma scale
      (GCS), with recording by 20 Board-certified neurosurgeons. RESULTS: The 7050
      cases collected included 5322 hospitalized cases, 1694 cases seen in the
      Emergency Room, and 34 deaths on arrival. The leading cause of head injuries was
      traffic accidents (5354 cases, 76.3%). Motorcycles contributed to the highest
      number of cases (3661, 68.4%); and trains contributed to the lowest number (8,
      0.1%). Helmets were used in only 5.2% of 3503 motorcycle accidents. Based on the
      patients' or families' description in 4835 cases, the leading cause of the
      accident was careless driving (1180 cases, 24.4%). The 1088 cases of severe head
      injury were classified with a score less than 8 by the GCS; 498 of them died, or
      an 86.6% mortality (575 cases). CONCLUSIONS: Traffic accidents are the leading
      cause of head injuries, and motorcycles contribute to the major part of it in
      central Taiwan. Similar conclusions can be drawn for other areas including Taipei
      City, Taipei area, and Hualian County.

PMID- 7712396
TI  - Transesophageal indirect atrial pacing for open-heart surgery in children.
AB  - BACKGROUND: Transesophageal atrial pacing (TAP) has been successfully applied for
      clinical use for more than 30 years. Not only for cardiac pacing, or diagnosis
      and treatment of rhythmic disturbance but also for assessing the presence and
      severity of coronary artery disease and maintaining adequate heart rate can TAP
      provide satisfactory effect. In this study we applied TAP on children undergoing
      the cardiac surgery to evaluate its efficacy and side effects during such major
      surgery. METHODS: Twenty-four children (15 M and 9 F) undergoing open-heart
      surgery with informed consents were included in this study. After induction of
      anesthesia the bipolar pacing electrode (Tapcath, Arzco Medical Electronics) was
      inserted into esophagus through the nose until the ideal site for atrial pacing
      was found by monitoring the esophageal ECG lead (lead I), and then initiation of
      atrial pacing was performed by applying the transesophageal cardiac stimulator
      (Arzco Medical Electronics). Continuous ECG, arterial blood pressure and central
      venous pressure (CVP) were simultaneously monitored and recorded. Patient's
      height, inserted length of the pacing electrode, current and pulse duration for
      effective atrial pacing were also recorded. RESULTS: The effective rate for
      initiating sinus tachycardia (atrial capture) by applying TAP was 79.2% (19/24)
      in our study. For effective atrial pacing the average current was 11.6 +/- 2.4
      mA, the average stimulus pulse duration was 4.8 +/- 1.0 ms, and the average
      inserted length of bipolar electrode was 19.1 +/- 2.2 cm. CONCLUSIONS: TAP method
      can be applied satisfactorily in children undergoing cardiac surgery. If urgent
      cardiac pacing must be applied in these patients TAP would be a choice.

PMID- 7712397
TI  - Amoxicillin/clavulanic acid associated cholestasis in a patient with chronic
      hepatitis B: a case report.
AB  - We described a patient with history of chronic hepatitis B in whom cholestatic
      hepatitis occurred after amoxicillin/clavulanic acid (Augmentin) therapy, which
      to our knowledge is the first case reported in Asia. An atypical serology profile
      of hepatitis B virus (HBV) markers, demonstrated by negative hepatitis B surface
      antigen (HBsAg) associated with transient positivity of hepatitis B e antigen
      (HBeAg) and HBV DNA, was noted during the development of cholestasis.

PMID- 7712398
TI  - Acquired immunodeficiency syndrome with CNS toxoplasmosis: a case report.
AB  - Central nervous system (CNS) toxoplasmosis is an important infectious
      complication of acquired immunodeficiency syndrome (AIDS) which appears to result
      from reactivation of a previously acquired infection and requires prolonged
      treatment. A 31-year-old male presented in a drowsy mental state and with an
      unstable gait. Computerized tomographic (CT) scan and magnetic resonance imaging
      (MRI) showed multiple nodular lesions in the cerebrum and cerebellum; the
      seropositivity for the human immunodeficiency virus (HIV-1) and high serum IgG
      toxoplasma titers were also demonstrated. A presumptive diagnosis of CNS
      toxoplasmosis was based on neurological signs and neuroradiological findings.
      This was confirmed by improvement in both clinical and neuroradiological pictures
      during treatment with pyrimethamine and clindamycin. Four months later, however
      the patient died of intracranial hemorrhage and massive upper GI bleeding.

PMID- 7712399
TI  - Central pontine myelinolysis in chronic hyponatremic patient: a case report.
AB  - A 59-year-old woman had chronic hyponatremia from inappropriate secretion of
      antidiuretic hormone (SIADH) and malnutrition after recurrent cholecystitis for 2
      months. She developed dysarthria, dysphagia, bilateral ptosis, clonic convulsions
      and delayed onset Parkinsonian features. Magnetic resonance imaging showed
      increased signal density in the central pons on T2-weighted images. She was also
      later diagnosed as having systemic lupus erythematosus (SLE). This case is
      reported because central pontine myelinolysis (CPM) developed in chronic
      hyponatremia without correction, and manifested with atypical, delayed-onset
      Parkinsonian features. The patient recovered well from her neurological illness,
      unlike the poor outcome in previously reported cases of CPM. In addition, the
      coincidence of CPM and SLE has not, to knowledge, been reported before.

PMID- 7712400
TI  - Hypothalamic hamartoma and gelastic epilepsy: a case report.
AB  - We studied a 6-year-old girl who presented with inappropriate and uncontrollable
      laughing episodes since age 3. Physical examination revealed a precocious
      puberty. The luteinizing hormone-releasing hormone (LH-RH) stimulation test
      showed an increased level of follicle-stimulating hormone (FSH). The interictal
      electroencephalogram (EEG) was normal. Several laughing fits were documented
      during video/EEG monitoring. During laughing, the ictal EEG showed a diffuse
      suppression of background rhythm, prominent over the left mesial temporal region.
      A mass lesion about 2 x 2 cm in size was found over the suprasellar cistern with
      a broad base attached to the hypothalamus, which was isodense on a computed
      tomography (CT) scan, isointense to gray matter on T1-weighted magnetic resonance
      (MR) imaging and hyperintense on T2-weighted MR imaging. The findings were
      suggestive of a hypothalamic hamartoma. A variety of anticonvulsants had been
      used with little or no response to the frequency or duration of the laughing
      seizures.

PMID- 7712401
TI  - Coexisting IgA nephropathy and leukocytoclastic cutaneous vasculitis associated
      with ankylosing spondylitis: a case report.
AB  - A patient with ankylosing spondylitis and coexisting IgA nephropathy and
      leukocytoclastic cutaneous vasculitis is described. Renal biopsy demonstrated
      mesangial proliferative glomerulonephritis with prominent IgA, C3 and fibrin
      deposition in the glomeruli. Simultaneously, leukocytoclastic cutaneous
      vasculitis with prominent IgG, IgA and C3 deposition of dermal vessel wall was
      also observed in the skin biopsy specimen. Such associations have been previously
      reported in only four cases. This report once again indicates that antigenic
      mucosal stimulation may play an important role in the pathogenesis of ankylosing
      spondylitis.

PMID- 7712402
TI  - Treatment of an adult with neglected congenital pseudoarthrosis of the tibia with
      acute fracture: a case report.
AB  - Treatment of congenital pseudoarthrosis of the tibia is very difficult. Numerous
      surgical procedures have been used including bone grafting, fixation, pulsed
      electromagnetic field, vascularized fibular bone grafting and lengthening
      devices. Previous studies, often reporting unsatisfactory results, are limited to
      children and adolescents. In adults, the following factors need to be considered:
      leg length discrepancy, leg deformity, soft tissue problems, lack of potential
      for growth and difficulties in healing. We reported a case of untreated
      congenital pseudoarthrosis of the tibia with fracture in a 32-year-old man.
      Conventional treatments used included excision of the pseudoarthrosis, correction
      of the deformity, intramedullary fixation, bone grafting and soft tissue
      transplantation for lengthening and coverage. These procedures led to good bony
      union and a satisfactory outcome.

PMID- 7712403
TI  - Nursing thesis database project: a cooperative venture for nursing faculty and
      computer science professionals.
AB  - The authors describe the development of an educational database project designed
      to promote the accessibility of nursing administration theses data for graduate
      students and faculty in a university nursing administration program. The roles of
      a nursing faculty member, a computer laboratory administrator, and a programmer
      are detailed as they work together from the concept phase of the project through
      its evaluation. The results of their combined efforts provided a reliable and
      efficient database, resulted in a closer interdisciplinary relationship, and
      allowed valuable nursing research information to be shared more widely within the
      university.

PMID- 7712404
TI  - Nursing student information network: fostering collegial communications using a
      computer conference.
AB  - This article describes the development and implementation of a student-based
      computer information network in a university setting. A computer conference was
      established as a pilot project on two campuses in a large multipurpose,
      multicampus university school of nursing, and it was used to communicate
      information and facilitate collegial interaction among students, faculty,
      academic counselors, and administrators. The project demonstrates that computer
      conferences can be used to disseminate information effectively to diverse and
      geographically distant student populations. Such networks have the potential to
      enhance opportunities for collaborative learning experiences and student-faculty
      communication.

PMID- 7712405
TI  - Description of a graduate program in clinical nursing informatics.
AB  - This article describes the history and development of the Clinical Nursing
      Informatics Program at the University of Utah College of Nursing. Program
      philosophy and curriculum are discussed in the context of the conceptual
      framework. Courses and student projects are described. The authors reflect on the
      ensuing stage of program development.

PMID- 7712406
TI  - Faculty authoring of course-specific software for disadvantaged nursing students
      using LinkWay: a case study.
AB  - This article adds to the literature on the use of hypermedia systems for software
      development in nursing education by describing design and authoring
      considerations in the construction of course-specific remediating software. In
      1991, under the guidance of an instructional designer, faculty members developed
      LinkWay folders on aspects of the endocrine system for remedial use by students
      in Project Get Ahead in Nursing at Southern Illinois University at Edwardsville.
      Existing content outlines were modified according to design criteria, including
      representing information graphically, making the software translation
      interactive, embedding visual prompts and cues, and conforming to a specific
      design protocol. The use of LinkWay in facilitating the implementation of both
      procedural of both procedural and screen protocol is discussed, and several
      screen templates are presented, including menus, multiple choice, short answer,
      multiple choice browsing, and end-of-section evaluation. Current project status
      and conclusions for remediation using a hypermedia approach are discussed.

PMID- 7712407
TI  - Applied information technology: a clinical perspective: Feature focus: the
      computer-based patient record (part 1).

PMID- 7712409
TI  - Guidelines for interaction with the pharmaceutical industry.

PMID- 7712408
TI  - [Academic medicine and the pharmaceutical industry].

PMID- 7712410
TI  - Folate to prevent neural tube defects.

PMID- 7712411
TI  - Folate to prevent neural tube defects.

PMID- 7712412
TI  - Cycling safety and accident prevention.

PMID- 7712413
TI  - Cycling safety and accident prevention.

PMID- 7712415
TI  - Cycling safety and accident prevention.

PMID- 7712414
TI  - Cycling safety and accident prevention.

PMID- 7712416
TI  - Beyond universal precautions.
AB  - Universal precautions have gained wide acceptance in the literature and are
      promoted by major health care regulatory bodies as a measure to prevent
      nosocomial transmission of bloodborne diseases. Nevertheless, Dr. James G. Wright
      and associates (see pages 1089 to 1095 of this issue) provide evidence of the
      infrequent use of universal precautions by surgeons in Toronto. Their findings
      are consistent with those of similar studies and point to the limitations of any
      safety approach that relies on the active compliance of individuals rather than
      on passive, environmental controls. Successful approaches to optimizing workplace
      safety should first emphasize passive measures for risk abatement, including firm
      policies, the use of safer equipment and techniques, procedural safeguards and
      regular monitoring. Routine voluntary screening of patients undergoing procedures
      that pose a high risk of contamination may improve compliance to safety
      procedures by health care personnel. Further study is required.

PMID- 7712417
TI  - HIV-infected physicians: how best to protect the public?
AB  - The debate about public safety as it relates to physicians living with HIV
      infection concerns all Canadians. A review of the evidence strongly suggests that
      the best way to protect the public is by strict adherence to universal
      precautions and the voluntary use of expert advisory panels on an anonymous
      basis. Mandatory reporting of the identities of HIV-positive physicians and the
      use of expert panels that have the authority to ban doctors from doing certain
      procedures would only lead to fewer doctors at risk for HIV infection coming
      forward for testing and treatment and to mandatory testing for all.

PMID- 7712418
TI  - Core and comprehensive health care services: 1. Introduction to the Canadian
      Medical Association's decision-making framework.
AB  - The CMA's decision-making framework on core (i.e., publicly funded) and
      comprehensive health care services emphasizes flexibility and recognizes three
      levels at which decisions can be made: between patients and physicians (micro),
      in the community or by society (meso) and by governments (macro). Three major
      content dimensions are considered quality of care (e.g., effectiveness,
      appropriateness and efficiency of health care services), ethics (e.g., decisions
      that reflect fairness and acceptability to patients and physicians) and economics
      (e.g., measurement of service costs against economic benefits in a time of severe
      economic restraint). There are challenges in applying the framework; however, by
      providing decision-makers with the knowledge and tools needed to assist in the
      process, it is hoped that the first and foremost concern will continue to be the
      quality of patient care so highly valued by Canadians.

PMID- 7712419
TI  - Physician awareness of fetal alcohol syndrome: a survey of pediatricians and
      general practitioners.
AB  - OBJECTIVE: To determine the knowledge, clinical experience and perceived needs
      for resource materials of Saskatchewan physicians in regard to fetal alcohol
      syndrome (FAS) and alcohol-related birth defects. DESIGN: Mailed survey. SETTING:
      Saskatchewan. PARTICIPANTS: All 48 pediatricians and half (394) of the family
      physicians (FPs) and general practitioners (GPs) practising in Saskatchewan
      received a questionnaire. The numbers of physicians who completed it were 24 and
      249 respectively. RESULTS: The pediatricians were more likely than the other
      physicians to be aware of FAS and to have diagnosed at least one case of FAS.
      Among the FPs and GPs, the year of graduation from medical school was a
      significant factor in their knowledge of FAS and their diagnostic practices.
      Those who graduated before 1974, the year FAS was first described in the medical
      literature, were less likely than the more recent graduates to be aware of FAS
      and to ask their patients about alcohol use during pregnancy but were more likely
      to feel comfortable discussing alcohol-related issues in families. All of the
      groups reported a need for more information about FAS and for resources on
      alcohol-related issues in general. CONCLUSIONS: Saskatchewan physicians are aware
      of FAS but have expressed a need for more information about FAS, particularly for
      parents, as well as physician training materials and information about where to
      refer patients with FAS and parents with alcohol-related problems.

PMID- 7712420
TI  - Blood lead levels in children aged 24 to 36 months in Vancouver.
AB  - OBJECTIVES: To determine the blood lead levels in children and to identify risk
      factors for elevated levels. DESIGN: Cross-sectional study. SETTING: Vancouver.
      PARTICIPANTS: Random sample of children aged 24 to 36 months, born and still
      resident in Vancouver. The sample was stratified proportionally by the median
      annual family income in the census tract where each family resided. OUTCOME
      MEASURES: Blood lead levels and risk factors for elevated blood lead levels,
      determined from a questionnaire administered to parents. RESULTS: Of the children
      in the sample, 42% (178/422) were ineligible or could not be located. Of the
      remaining children, 73% (177/244) participated and adequate blood specimens were
      obtained from 172. The mean blood lead level was 0.29 mumol/L (standard deviation
      0.13 mumol/L). (A blood lead level of 1 mumol/L is equivalent to 20.7
      micrograms/dL.) The lowest level was 0.06 mumol/L, and the highest was 0.85
      mumol/L. Of children with adequate samples, 8.1% (14/172) had blood lead levels
      of 0.48 mumol/L or higher, and 0.6% (1/172) had a level higher than 0.72 mumol/L.
      The logarithms of the levels were normally distributed, with a geometric mean
      (GM) of 0.26 mumol/L (geometric standard deviation 1.56). Of approximately 70
      possible predictors of blood lead levels analysed, those that showed a
      statistically significant association (p < 0.05) with increased blood lead levels
      were soldering performed in the home as part of an electronics hobby (GM blood
      lead level 0.34 mumol/L, 95% confidence interval [CI] 0.27 to 0.39 mumol/L),
      aboriginal heritage (GM blood lead level 0.33 mumol/L, 95% CI 0.28 to 0.39
      mumol/L), dwelling built before 1921 (GM blood lead level 0.32 mumol/L, 95% CI
      0.28 to 0.37 mumol/L), age of water service connection to dwelling (predicted
      blood lead level 0.00087 mumol/L [95% CI 0.00005 to 0.00169 mumol/L] higher per
      year since service connection) and decreased stature (predicted blood lead level
      0.018 mumol/L [95% CI 0.0353 to 0.0015 mumol/L] higher for every standard
      deviation below the age-specific mean height). CONCLUSIONS: This study found much
      lower blood lead levels in children than those found in previous Canadian
      studies. The authors believe that this result is not an artefact due to
      differences in population sampling or methods of collection of blood specimens.
      The study showed no clear risk factors for elevated blood lead levels: although a
      few factors had a statistically significant association with increased blood lead
      levels, the differences in levels were small and unimportant.

PMID- 7712422
TI  - Canada's AIDS toll mounts.

PMID- 7712421
TI  - Reported use of strategies by surgeons to prevent transmission of bloodborne
      diseases.
AB  - OBJECTIVE: To determine how often surgeons use strategies to prevent the
      transmission of bloodborne diseases and what factors are associated with the use
      of these strategies. DESIGN: Cross-sectional mail survey. SETTING: Secondary and
      tertiary care teaching hospitals affiliated with the University of Toronto.
      PARTICIPANTS: Of 539 active surgical staff and residents who were eligible, 503
      (93.3%) responded. OUTCOME MEASURES: Current preventive practices, attitudes
      toward transmission of bloodborne diseases, perceived risk of infection and
      willingness to adopt preventive strategies. RESULTS: On average, surgeons
      reported using double- or triple-gloving in 32.2% of procedures, facial
      protection (including regular corrective eyewear) in 74.2% and goggles or face
      shields in 19.4%. Use of strategies to prevent sharp injuries, in addition to
      barrier precautions, was reported by 259 (51.5%) of the respondents. Factors
      associated with greater use of preventive strategies included resident position,
      subspecialty, greater number of years in surgical practice and a high perceived
      risk. Most of the respondents thought that patients should be routinely screened
      for HIV antibodies before surgery (68.2% [343/503]), that there was too little
      research into ways to reduce the risk of transmission of bloodborne diseases
      (55.3% [278/503]) and that there was too little effort on the part of
      organizations to reduce the risk of transmission (58.8% [296/503]). The perceived
      lifetime risk was reported to be moderate or high by 191 (38.0%) of the
      respondents and low or insignificant by 308 (61.2%). In all, 463 (92.0%)
      indicated a willingness to change the way they performed surgery to prevent
      transmission of bloodborne diseases. CONCLUSION: Surgeons expressed varying
      degrees of concern about the transmission of bloodborne diseases and reported
      infrequent use of preventive strategies. Efforts to reduce the risk of
      transmission between patients and surgeons will need to include informing
      surgeons of their personal risk and the availability of preventive strategies,
      improving the comfort of barrier precautions and minimizing how preventive
      strategies interfere with surgery.

PMID- 7712423
TI  - Research institute tries to ease brain drain by bringing researchers back to
      Canada.
AB  - The lack of research opportunities in Canada and the large number of them in the
      US have cost Canada some of its brightest young researchers. The Robarts Research
      Institute in London, Ont., is trying to reverse that trend by bringing some of
      these researchers back home. However, Dr. Mark Poznansky says the repatriation
      efforts will mean little if research budgets keep getting cut in Canada. He says
      the budget of the Medical Research Council of Canada is barely adequate for
      today's needs.

PMID- 7712424
TI  - Pain during childbirth leads to $2.4-million lawsuit.
AB  - A woman from Hamilton, Ont., is suing a local hospital an three physicians,
      alleging that she suffered excessive pain while giving birth. The first-time
      mother alleges that she experienced excessive pain during delivery despite her
      repeated requests for pain relief.

PMID- 7712426
TI  - Different fates await authors after two journal reports declared invalid in UK.
AB  - Two London gynecologists have left their positions in disgrace amid accusations
      of fraud connected with two research papers published in a British obstetrics
      journal. The merger of four medical schools, the first stage of the closure of
      the eminent St. Bartholomew's Hospital and hospital trust appointments also
      caught the attention of our London correspondent.

PMID- 7712425
TI  - Intervention in elder abuse: a swift blade, or a dull-edged saw?
AB  - In spite of a geriatric team's offer to intervene in what was perceived to be a
      case of psychologic and financial abuse, an elderly patient who was being
      discharged from hospital chose to remain in her home. Frustration and concern
      about the victim prompted medical student Kim Curtin to write this essay that
      considers the issues of judgement, beneficence and medical intervention.

PMID- 7712427
TI  - Saskatchewan physicians chided over public criticism of colleagues.

PMID- 7712428
TI  - A phase II trial of interferon alpha-2A, 5-fluorouracil, and cisplatin in
      patients with advanced esophageal carcinoma.
AB  - BACKGROUND: The combination of 5-fluorouracil (5-FU) and cisplatin has moderate
      antitumor activity in the treatment of metastatic epidermoid carcinoma of the
      esophagus. The authors have recently shown activity for the combination of 5-FU
      and interferon-alpha 2a (IFN-alpha) in both esophageal epidermoid and
      adenocarcinoma. A Phase II trial, therefore, was undertaken to evaluate the
      antitumor activity of the three-drug combination of IFN-alpha, 5-FU, and
      cisplatin in unresectable or metastatic esophageal carcinoma. METHODS: Twenty
      seven patients with locally advanced or metastatic carcinoma of the esophagus
      were treated. No prior chemotherapy was allowed. Twelve patients had epidermoid
      carcinoma (44%) and 15 patients had adenocarcinoma (56%). Patients received IFN
      alpha at a dose of 3 x 10(6) units/day given daily by subcutaneous injection on
      days 1 to 28, 5-FU at a dose of 750 mg/m2/day for 5 days by continuous
      intravenous infusion on days 1 to 5, and cisplatin at a dose of 100 mg/m2 on day
      1. Treatment was recycled every 28 days, and after the first three cycles,
      cisplatin was administered only on alternate cycles. Twenty-seven patients
      completed a median of 4 cycles (range, 1-13 cycles), and 26 patients were
      evaluable for response. RESULTS: Major responses were observed in 13 patients
      (50%, 95% confidence intervals, 31-69%), including two complete responses (8%).
      The response proportion in epidermoid carcinoma (8 of 11 patients, 73%) was
      higher than the response proportion in adenocarcinoma (5 of 15 patients, 33%).
      The median duration of response was 29 weeks (range, 11-74 weeks), similar in
      epidermoid carcinoma and adenocarcinoma. Toxicity was moderately severe but
      manageable with dose attenuations. Grade 3/4 hematologic toxicity was observed in
      41% of patients and grade 3/4 nonhematologic toxicity was observed in 26% of
      patients. IFN-alpha was reduced to either a 3- or 5-day a week schedule because
      of fatigue and/or myelosuppression in 12 patients (44%). There were two treatment
      related deaths (7%). CONCLUSION: In this Phase II trial, the combination of IFN
      alpha, 5-FU, and cisplatin had substantial antitumor activity in esophageal
      carcinoma with apparently greater antitumor activity in epidermoid carcinoma than
      adenocarcinoma. A larger confirmatory trial comparing this treatment to
      conventional 5-FU and cisplatin is warranted for epidermoid carcinoma. In future
      chemotherapy trials, the response assessment for epidermoid and adenocarcinoma
      should continue to be stratified.

PMID- 7712429
TI  - Immunohistochemical evaluation of bcl-2 protein expression in gastric
      adenocarcinomas.
AB  - BACKGROUND: bcl-2 protooncogene encodes for a 26 kD protein effective in
      inhibiting programmed cell death (apoptosis). Its expression has been noted in
      lymphomas and colonic, lung, and breast carcinomas. bcl-2 protein is believed to
      play a role in the gastric carcinogenic sequence where it has been demonstrated
      in dysplastic epithelium. To further study the role of bcl-2 protein in gastric
      carcinogenesis and tumor progression, an immunohistochemical study of bcl-2
      expression in gastric adenocarcinomas and its relation to the histologic type,
      grade of differentiation, pT stage, lymph node status, and survival was
      performed. METHODS: Immunohistochemical staining using monoclonal bcl-2 protein
      antibody, clone 124, was performed on archival material. RESULTS: Forty-six of
      the sixty-four adenocarcinomas (72%) showed bcl-2 staining with immunoreactivity
      in 75% of the tumor or more. No specific pattern in the distribution of labeling
      was seen. bcl-2 reactivity was significantly associated with adenocarcinomas of
      the intestinal morphotype. Forty-five of 51 intestinal-type tumors (88%) were
      immunoreactive versus only 1 of the "diffuse" tumors (7%) (P = 0.001). Within the
      intestinal-type adenocarcinomas, a trend of increasing prevalence of
      immunoreactivity with higher histologic grades was seen. No correlation between
      bcl-2 expression and pT stage, lymph node status, or survival was observed.
      CONCLUSION: bcl-2 expression in gastric adenocarcinoma appears to be associated
      almost exclusively with the intestinal morphotype and to some extent is more
      prevalent in grade 3 tumors. No correlation was noted with the pT stage, lymph
      node status, and survival. Inhibition of apoptosis through bcl-2 protein
      expression appears to be specifically associated with promotion of intestinal
      type gastric adenocarcinoma but does not appear to be active and/or correlated
      with tumor progression.

PMID- 7712430
TI  - Mutations of the p53 gene in male breast cancer.
AB  - BACKGROUND: Cancer of the male breast (MBC) is rare, accounting for less than 1%
      of cancer in males and representing less than 1% of all breast cancers. Reports
      of abnormalities in the expression of the tumor suppressor gene p53 in MBC have
      been few. METHODS: To assess the expression and mutations of the p53 gene, 35
      patients with 36 MBC (one patient with bilateral breast carcinoma) were examined
      using immunohistochemical methods, polymerase chain reaction (PCR)-single strand
      conformation polymorphism and DNA sequencing. RESULTS: Thirty-one of the 36
      carcinomas were studied by immunohistochemistry and by the PCR-based approach.
      Five patients were studied by immunohistochemistry only. Twelve patients (41.4%)
      of the 29 studied by molecular analysis presented an altered pattern in the
      single strand conformation polymorphism gel and point mutations were confirmed in
      all by direct DNA sequencing. Thirty-six tumors were studied by
      immunohistochemistry and 2 (5.5%) patients showed overexpression of the p53
      protein. There were no statistically significant differences in p53 status with
      respect to: age, stage, estrogen receptors, progesterone receptors, tumor type.
      Patients with normal p53 showed a predisposition, although not statistically
      significant, for a longer disease free survival (5.6 years versus 4.2 years) and
      overall survival (5.9 years versus 4.8 years) than did patients with genetically
      altered p53. CONCLUSIONS: The incidence of male patients detected with p53
      mutations (41.4%) in this series is concordant with the incidence of p53
      mutations in female breast cancer, supporting the idea that cancer of the male
      breast is similar to the female counterpart.

PMID- 7712431
TI  - Uterine papillary serous carcinoma. A clinical study.
AB  - BACKGROUND: Uterine papillary serous carcinoma (UPSC) is a histologic subtype of
      endometrial adenocarcinoma that is characterized by its papillary architecture,
      poor differentiation, and advanced stage at initial presentation. It behaves more
      aggressively than the more common endometrioid adenocarcinoma of the endometrium.
      METHODS: The history, treatment and follow-up of 18 women with UPSC were
      evaluated. RESULTS: All women underwent total hysterectomy and bilateral
      salpingoophorectomy. Positive lymph nodes were found in 6 of 14 patients who
      underwent pelvic lymphadenectomy. Twelve of 18 women with UPSC had FIGO Stage III
      and IV tumors in contrast to 30 of 236 patients with endometrioid adenocarcinoma
      (P < 000.1). Subsequent treatment of these women was: radiotherapy, three women;
      chemotherapy, four, both radiotherapy and chemotherapy, eight. Chemotherapy
      consisted of cisplatin/carboplatin plus cyclophosphamide. None of the patients
      with Stage I or II UPSC died of tumor during a mean follow-up of 31.6 months
      (range, 12-68 months). Of the women with Stage III and IV disease, 4 of 12 are
      alive with no evidence of disease after a mean follow-up of 22.5 months (range, 8
      45 months). Eight of 12 women who received chemotherapy are alive with no
      evidence of disease, 4 of whom had Stage III or IV disease. One of six women who
      did not receive chemotherapy is alive, three died of tumor, and two of
      intercurrent disease. CONCLUSION: These results would justify further study of
      the possible role of platinum-based chemotherapy in patients with uterine
      papillary serous carcinoma.

PMID- 7712432
TI  - Adult primary pure teratoma of the testis. The Indiana experience.
AB  - BACKGROUND: Pure testicular teratoma in adults is a relatively rare malignant
      tumor with the ability to invade and metastasize. Pure teratoma generally is
      believed to be less aggressive and less likely to progress, to present in lower
      stages, and to have better survival rates then other forms of germ cell tumor.
      Consequently, clinical stage A patients with pure testicular teratoma commonly
      have been considered to be managed best by surveillance. METHODS: A computerized
      database search identified 41 patients presenting to Indian University with pure
      teratoma in the orchiectomy specimen. These patients were further subdivided into
      four groups based on clinical stage, as follows: Group I, 18 patients with
      clinical Stage A disease; Group II, 4 patients with clinical Stages A-B1 disease
      based on questionable computed tomography findings; Group III, 3 patients with
      clinical Stage B1 disease; Group IV, 16 patients with advanced stage (B3-C)
      disease. The experience with these patients was reviewed. RESULTS: The overall
      risk of lymph node metastasis in retroperitoneal lymph node dissection (RPLND)
      and the risk of relapse after RPLND for patients with low stage pure testicular
      teratoma (groups I-III) were 40 and 16%, respectively. In patients with clinical
      Stage A teratoma, the risk of retroperitoneal metastasis in RPLND was 16.7% and
      the relapse rate was 11.1%. In addition, nearly 37% of referred patients with
      pure teratoma presented with advanced disease. CONCLUSIONS: These data provide
      additional confirmation of the metastatic potential of pure testicular teratoma.
      The proper management of the adult clinical stage A patient with primary pure
      teratoma of the testis should not necessarily differ from the management of any
      other histologic type of nonseminomatous testicular tumor. Accordingly,
      histologic diagnosis of pure teratoma should not mandate surveillance. Instead,
      patients must be given adequate information regarding management options, as are
      all other patients presenting with clinical Stage A nonseminoma.

PMID- 7712433
TI  - Primary renal non-Hodgkin's lymphoma. An unusual extranodal site.
AB  - BACKGROUND: Primary renal non-Hodgkin's lymphoma (NHL) is rare. Because the renal
      parenchyma does not have lymphatics, the existence of this entity has been
      questioned. The goal of this study was to determine the clinical presentation,
      pathologic features, and disease course of patients with primary renal NHL and
      review the pertinent literature on this unusual extranodal NHL. METHODS: All
      medical records from the Mayo Clinic from 1976 to 1992 with the diagnosis of
      renal NHL were retrospectively reviewed. One-hundred seventy-six cases were
      identified, five of which met the criteria for primary renal NHL. The clinical,
      pathologic, and radiographic features were reviewed in detail and are the basis
      of this report. RESULTS: The median age at diagnosis of the five patients with
      primary renal NHL was 60 years (range, 52-63 years) with a male-to-female ratio
      of 2:3. All patients had flank pain as their initial presentation. Urinalysis was
      abnormal in only one patient. In three patients, the serum creatinine was
      elevated. Tumor histology was diffuse large cell in four cases; and small
      noncleaved non-Burkitt's in one. All five were B-cell immunophenotype. All
      patients received combination chemotherapy. Although the median survival for the
      group was only eight months, two remain in complete remission longer than 80
      months from therapy. These two had total removal of macroscopic lymphoma and
      received combination chemotherapy and consolidation radiotherapy. CONCLUSIONS:
      Primary renal non-Hodgkin's lymphoma does exist. Patients whose lymphomas were
      completely resected macroscopically and who received combination chemotherapy
      with consolidation radiation therapy had long disease free survival. Patients
      with bilateral renal involvement or no debulking of the renal lymphoma tended to
      have poorer survival.

PMID- 7712434
TI  - Lack of radiosensitization after paclitaxel treatment of three human carcinoma
      cell lines.
AB  - BACKGROUND: Several recent studies have suggested radiosensitizing effects of
      paclitaxel, a microtubular inhibitor. To test the universality of this finding,
      the interaction between paclitaxel and radiation treatment of cell lines derived
      from three common human carcinomas MCF-7 (breast cancer); DUT-145 (prostate
      cancer); and HT-29 (colon cancer) was evaluated. The study focused on the ability
      of paclitaxel to block cells at the G2-M phase of the cell cycle and potentially
      enhance the radiation sensitivity of the cells. METHODS: All cell lines were
      exposed to three different clinically achievable paclitaxel concentrations
      ranging from 2 nM to 25 nM. Paclitaxel pretreatment for 12 and 24 hours before
      radiation was tested in all three cell lines. The radiation dose ranged from 0 to
      8 Gy delivered in a single fraction. Cellular survival after treatment with
      paclitaxel and/or radiation was determined by clonogenic assay. Cell cycle
      distribution as determined by flow cytometry was performed after various dose
      time combinations of paclitaxel. RESULTS: Cytotoxicity studies with paclitaxel
      alone demonstrated a time-dependent and dose-dependent survival relationship for
      all three cell lines. Resultant surviving fractions were in the range of 5 to 90%
      after 24-hour exposure to paclitaxel alone. The interaction between paclitaxel
      and radiation was primarily additive in each of the three cell lines for all
      paclitaxel dose-time combinations studied. Flow cytometric analysis failed to
      reveal a prominent G2-M block in all three cell lines after paclitaxel treatment
      for 24 hours. CONCLUSIONS: Paclitaxel lacked a radiosensitizing effect on MCF-7,
      DUT-145, and HT-29 cells in this study. These results should be considered when
      designing clinical trials that use paclitaxel as a potential radiosensitizer of
      certain human carcinomas.

PMID- 7712435
TI  - The Stockholm I trial of preoperative short term radiotherapy in operable rectal
      carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study
      Group.
AB  - BACKGROUND: From 1980 to 1987, 849 patients with clinically resectable rectal
      adenocarcinoma were randomized into a controlled clinical trial to evaluate the
      role of preoperative radiotherapy. METHODS: Patients were given either 25 Gy
      during 5 to 7 days before surgery or underwent surgery alone. RESULTS: At a
      median follow-up time of 107 months (range, 62-144 months) the incidence of
      pelvic recurrence among 684 "curatively" operated patients was significantly
      lower among those who also received radiotherapy (P < 0.001) in all Dukes'
      stages. No significant difference was observed between the treatment groups with
      regard to frequency of distant metastases or overall survival. The time to local
      recurrence or distant metastasis and survival was significantly prolonged in the
      irradiated group. However, the postoperative mortality was 8% in the radiotherapy
      group compared with 2% in the surgery only group (P = 0.01). CONCLUSIONS:
      Preoperative short term radiotherapy reduced the incidence of pelvic recurrences
      and prolonged survival related to rectal cancer compared with surgery alone. The
      postoperative morbidity was significantly higher in the irradiated group.

PMID- 7712436
TI  - A pilot study of combination therapy of radiation and local administration of OK
      432 for esophageal cancer. Five-year survival and local control rate.
AB  - BACKGROUND: Combination therapy consisting of radiation and local administration
      of OK-432 was administered to 73 patients with esophageal cancer without distant
      metastases. Seventy patients were examined. The average age was 71 years. There
      were 60 males and 10 females. The mean tumor length was 7.0 cm. METHODS: One mg
      of OK-432 was administered endoscopically to and around the cancerous lesion at
      the beginning of radiotherapy and a second dose of 0.5 mg of OK-432 was given in
      the same manner 2 weeks later. X-ray irradiation was given at a daily dose of 1.6
      1.8 Gy, five fractions a week. The average total dose was 61.1 Gy. RESULTS:
      Complete responses were obtained in 49 of the 70 patients (70.0%), and partial
      responses (PR) in the remaining 21. The 5-year cause-specific survival rate of
      the 70 patients was 33.1%. The 5-year survival rate of the 49 patients with CR
      was 44.9%, and there were no patients with PR who survived more than 2 years. The
      5-year survival rate of the 13 patients with T1 (UICC, 1987) was 79.6%, of the 24
      patients with T2/3 41.1%, and of the 33 patients with T4 11.6%. The 5-year
      survival rates of the 18 patients with tumors less than 5 cm in length and the 40
      patients with tumors 5 to 10 cm were 59.9 and 37.9%, respectively. In the
      patients with tumors more than 10 cm in length, the 4-year survival rate was
      14.6%. Sixty-nine of the 70 patients were discharged in good condition and were
      able to take food orally. CONCLUSIONS: This combination therapy may contribute
      not only to the survival rate, but also to patients' quality of life.

PMID- 7712437
TI  - Increased risk of second malignant neoplasms outside radiation fields in patients
      with cervical carcinoma.
AB  - BACKGROUND: The relative risk of second primary cancers was evaluated in 125
      women with International Federation of Gynecology and Obstetrics (FIGO) Stages I
      and II cervical carcinoma treated radically with radiation therapy between
      January 1980 and December 1990. METHODS: Medical records of patients were
      reviewed to evaluate the incidence of second malignant neoplasms. Only tumors
      histologically proven were scored. The annual 5-year age-specific cancer
      incidence data per 100,000 white women in the years 1981-1985 were obtained from
      the National Cancer Institute's Surveillance, Epidemiology and End Results
      database. The relative risks were calculated as the ratio of observed-to-expected
      numbers of second cancers, using person-years at risk accumulated for each
      individual in the study. RESULTS: During the follow-up time (through December
      1992), 10 women whose median age was 65.5 years at the time cervical cancer was
      diagnosed were found to have 11 second primary cancers. Nine of these cancers
      were metachronous with regard to cervical cancer and included breast (4), lung
      (2), myeloma (1), non-Hodgkin's lymphoma (1) and vulva(1). The metachronous
      tumors were diagnosed at a median age of 74 years and at median follow-up time of
      34 months. Two of the cancers were synchronous with cervical cancer and included
      bladder (1) and thyroid (1). All of the second tumors were located outside
      radiation fields. None of the patients with second tumors received chemotherapy
      during treatment for cervical carcinoma. The relative risk of developing a second
      cancer of any type was 2.31 (95% confidence interval [CI] = 1.15-4.13), whereas
      the relative risk of developing a metachronous breast cancer was 2.64 (95% CI =
      0.72-6.75). CONCLUSIONS: An increased risk of second primary cancers developing
      was observed among 125 patients with FIGO Stages I and II cervical carcinoma,
      which may suggest an abnormal genetic background and/or a common etiology for the
      initial and second tumors. The increased risk of breast cancer occurring as a
      second primary is in contrast with previously published studies reporting a
      decreased risk of breast cancer in survivors of cervical cancer.

PMID- 7712438
TI  - The variation of inguinal lymph node depth in adult women and its importance in
      planning elective irradiation for vulvar cancer.
AB  - BACKGROUND: The Gynecologic Oncology Group (GOG) protocol #88 reported an 18.5%
      failure in inguinal lymph nodes of patients with vulvar cancer whose groins were
      treated with radiation alone. This high failure rate may be due to the study
      design. METHODS: In this study, the depths of inguinal lymph nodes were evaluated
      with computed tomography (CT) scans in 100 adult women without inguinal
      adenopathy or prior inguinal surgery. The dose that would have been delivered to
      the inguinal lymph nodes of these patients was determined using isodose curves
      constructed according to the guidelines in GOG protocol #88. RESULTS: Only 18% of
      women had all inguinal lymph nodes measured at a depth of 3 cm or less.
      CONCLUSIONS: More than one-half of all women in this study would have received
      less than 60% of the prescribed radiation dose because their inguinal lymph nodes
      were deeper than 5 cm, if the depth of their inguinal lymph nodes had not been
      measured before therapy.

PMID- 7712439
TI  - Concurrent radiation therapy and chemotherapy in the treatment of primary
      squamous cell carcinoma of the vulva.
AB  - BACKGROUND: Interest in combined modality treatment and in quality of life issues
      may affect the choice of radical vulvectomy as the treatment of choice in many
      vulvar carcinomas. To evaluate the potential role of combined radiation and
      chemotherapy with or without local excision as primary treatment for squamous
      cell carcinoma of the vulva, the outccomes of 19 patients with this disease
      treated with combination therapy were reviewed. METHODS: Nineteen patients were
      treated between September 1987 and October 1992. Fifteen patients had American
      Joint Committee on Cancer Stage III disease; 4 had Stage II. All had clinically
      negative inguinal lymph nodes with the exception of two patients who had positive
      ipsilateral inguinal nodes that were removed before treatment. The patients
      received 45-50 Gy to the pelvis and inguinal nodes with concurrent chemotherapy
      that consisted of 5-fluorouracil given as a 96-hour continuous infusion (1000
      mg/m2/d) during weeks 1 and 5 of radiation. A single dose of mitomycin-C (10
      mg/m2) during the first day of chemotherapy has been used since November 1991.
      Ten patients were boosted with implants or electrons and 6 others underwent local
      excision. RESULTS: The median follow-up was 34 months. Responses were determined
      clinically 1 month after completion of the radiation and chemotherapy.
      Clinically, complete responses were obtained in 10 patients (53%), partial
      responses in 7 (37%), and no response in 1; 1 patient progressed during
      treatment. The combined modality therapy (radiation/chemotherapy/with or without
      wide local excision) resulted in a local control rate of 74% (14/19). All five
      treatment failures occurred within 6 months of treatment. Four of these patients
      were rendered disease free by radical vulvectomy and/or exenteration, for an
      overall local control rate of 95% (18/19). CONCLUSION: Concurrent radiation
      therapy and chemotherapy with local excision performed as needed, appears to be a
      reasonable alternative to radical vulvectomy in patients with primary squamous
      cell carcinoma of the vulva. Radical surgery remains a viable option for patients
      in whom primary therapy has failed.

PMID- 7712440
TI  - DNA ploidy of ovarian granulosa cell tumors. Lack of correlation between DNA
      index or proliferative index and outcome in 40 patients.
AB  - BACKGROUND: Most cases of granulosa cell tumor of the ovary are characterized by
      relatively good outcome; however, some tumors behave aggressively, and some tend
      to recur many years after the initial diagnosis. Because DNA ploidy has been
      shown to predict biologic behavior better than conventional prognostic variables
      in many types of genitourinary tumors, the DNA ploidy of granulosa cell tumors
      was studied to determine if this test correlates with recurrence or survival.
      METHODS: Paraffin embedded tissue blocks were available from the primary ovarian
      tumors of 40 patients. DNA ploidy, percent S-phase fraction, and proliferative
      index were determined for each sample and were compared with patient outcome.
      RESULTS: Of the 40 tumors, 33 were DNA diploid, 5 were DNA near
      diploid/aneuploid, and 2 were aneuploid. The Kaplan-Meier estimate of the
      probability of tumors not recurring within 5 years postoperatively was 0.907 (95%
      confidence interval: 0.811, 1.00). CONCLUSIONS: There is insufficient evidence to
      claim that the DNA pattern is associated with morphology, stage of disease at
      diagnosis, or tumor size or that either survival or progression free survival
      differs with respect to any of the conventional prognostic factors considered.
      However, progression free survival tends to be shorter for those whose maximal
      tumor dimension was at least 10 cm (borderline significance, P = 0.0597), and
      survival time tends to be shorter for those with a high proliferative index (P =
      0.0008).

PMID- 7712441
TI  - Preoperative regional therapy for extremity sarcoma. A tricenter update.
AB  - BACKGROUND: Preoperative radiation with sensitizing doxorubicin has been
      popularized in the treatment of high grade sarcoma of the extremity. A
      multiinstitutional experience with this protocol that was initiated by the
      Southeastern Cancer Study Group in 1984 and maintained in three institutions was
      updated by the authors. METHODS: Patients with biopsied sarcoma had intraarterial
      infusion with doxorubicin hydrochloride (Adriamycin) 30 mg/24 hrs x 3 days and
      were allocated by the institution to receive radiation 30-35 Gy in 10 fractions
      or 46 Gy in 23-25 fractions followed by resection. Surgery was performed within
      10 days or 30 days depending on the radiation dose. Postoperative chemotherapy
      was administered to 31 patients. RESULTS: Of 66 patients, 32 were female and 34
      were male. The median age was 46 years (range, 14-77 years); 73% had lower and
      27% had upper extremity tumors. There were 55 soft-tissue and 9 malignant bone
      tumors. Common types were malignant fibrous histiocytoma 20%; liposarcoma, 17%;
      synovial sarcoma 18%; and 14% were osteosarcoma. American Joint Committee on
      Cancer stages were: I, IIB (17%), IIIA/B (59%), and IIIC/4A (24%). Limb salvage
      surgery was performed on 60 patients including radical resection in 21 with
      extensive tumors, wide local excision in 30, and limited excision in 2 patients.
      Primary amputation was performed on four patients and delayed amputation in two
      because of wound complications. Three patients had pulmonary metastasectomy in
      conjunction with primary surgery (2 are long term survivors > 5 years). There
      were no postoperative deaths, but wound complications occurred in 41% of the
      patients. Overall survival and disease free survival at 5 years was 59 and 49%.
      One patient (1.5%) had local recurrence 9 years after resection of an extensive
      synovial sarcoma of the shoulder. This was resected with limb salvage techniques.
      Among 23 patients who failed primarily in the lung, the median survival was 7
      months with 4 surviving more than 5 years, after demonstration of the pulmonary
      metastases. Multivariant analysis of prognostic factors showed that extent of
      disease and stage correlated with disease free survival, whereas only extent of
      surgical resection correlated with overall surgical survival. CONCLUSION:
      Combined therapy for extremity sarcoma in a multicenter setting using
      preoperative radiation with sensitizing chemotherapy and adequate resection was
      associated with an excellent local control rate (98.5%) and reasonable long term
      tumor control, although distant metastases continued to be a major challenge.

PMID- 7712442
TI  - A majority of inverted sinonasal papillomas carries Epstein-Barr virus genomes.
AB  - BACKGROUND: The relationship between sinonasal inverted papilloma (IP) and
      various strains of human papilloma virus (HPV) has been examined previously. Yet
      there is little consensus regarding the incidence or role of HPV in IP. The
      possible role of Epstein-Barr virus (EBV), which, like HPV, is a DNA virus linked
      to human lymphoid and epithelial malignancies, was investigated. METHODS: The
      polymerase chain reaction (PCR) was used to detect EBV genomic sequences in
      surgical specimens of IP, in benign nasal polyps, and various control tissues.
      The IP specimens were similarly examined for the presence of HPV types 6, 11, 16,
      and 18. RESULTS: EBV DNA was found in 13 of 20 IP specimens (65%) and none of the
      10 control tissues. Nine of the 20 specimens contained HPV DNA, and 5 of 20
      specimens contained both EBV and HPV. CONCLUSIONS: These results imply a
      previously unsuspected role for Epstein-Barr virus in the pathogenesis of
      sinonasal inverted papilloma.

PMID- 7712443
TI  - Protection from radiation-induced chromosomal aberrations by the nitroxide
      Tempol.
AB  - BACKGROUND: The nitroxide Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl)
      is a stable, free radical that exhibits protection from ionizing radiation damage
      and from oxidative stress mediated through exposure of cells to superoxide or
      hydrogen peroxide. Radiation protection has been observed in both in vivo and in
      vitro models. To understand the mechanism of Tempol-mediated radioprotection
      better, the production of radiation-induced chromosome aberrations was evaluated.
      This study analyzed Tempol-mediated radioprotection of human peripheral blood
      lymphocytes (PBLs). METHODS: Peripheral blood lymphocytes were exposed to control
      (0mM), 10 mM (Tp10), and 50 mM (Tp50) concentrations of Tempol for 20 minutes
      before irradiation with 0, 150, 300, and 450 cGy. One quarter ml whole blood was
      cultured in F12 medium and phytohemagglutinin at 37 degrees C for 49, 54, 59, and
      64 hours. Colcemide was added to each sample for the last 5 hours before harvest.
      Cells were harvested, treated with hypotonic solution, and fixed before dropping
      on cold clean slides. Mitotic indices and frequency of dicentric, ring, and
      triradial chromosomal aberrations were determined at 1000x magnification for each
      treatment group at each collection point. RESULTS: Treatment of cells with Tempol
      alone did not induce the chromosomal aberration frequency above that for
      unirradiated controls. Radiation dose response curves for total chromosome
      aberration production revealed radioprotection for Tempol treatment for both 10
      and 50 mM exposures. Tempol protection factors (assessed at 0.2 aberrations/cell
      level) for Tp 10 and Tp 50 were 2.2 and 2.8, respectively. CONCLUSIONS: Tempol
      protects against radiation-induced chromosome aberrations in human PBLs. This
      finding is consistent with and lends support to previous studies in which Tempol
      was reported to enhance cell survival and reduce radiation-induced DNA double
      strand breaks.

PMID- 7712444
TI  - Ten-year results in 1070 patients with stages I and II breast cancer treated by
      conservative surgery and radiation therapy.
AB  - BACKGROUND: One thousand seventy patients treated conservatively for Stages I and
      II breast cancer between the years 1982 and 1994 were reviewed. The median follow
      up was 40 months with a maximum follow-up of 152 months. METHODS: All patients
      had a wide local excision and lower lymph axillary node dissection followed by
      radiation therapy. The entire breast received an external beam dose of 4500 cGy
      at 180 cGy/5 days/week. An additional boost dose of 2000 cGy to the tumor bed was
      given at the time of lumpectomy (perioperative) with an Ir-192 implant or with
      electron beam therapy after the external beam therapy. RESULTS: The 5- and 10
      year disease specific survival results were 97 and 90%, respectively for Stage I
      and 87 and 69% for patients with Stage II disease. The 5- and 10-year local
      control rates were 93 and 85% for Stage I and 92 and 87% for Stage II,
      respectively. The risk factors for local failure were premenopausal status and
      estrogen receptor-negative status at the univariate level but at the multivariate
      level the premenopausal and margins status were significant. CONCLUSION: These 10
      year results were at least equivalent to reported series of similarly staged
      patients treated by mastectomy. This should encourage more surgeons to offer
      conservative treatment as an alternative to mastectomy to patients with Stage I
      and II breast cancer.

PMID- 7712445
TI  - Concurrent hyperfractionated irradiation and chemotherapy for unresectable
      nonsmall cell lung cancer. Results of Radiation Therapy Oncology Group 90-15.
AB  - BACKGROUND: Clinical trials of hyperfractionated radiation therapy and induction
      chemotherapy followed by standard radiation therapy have shown improved survival
      in patients with unresectable nonsmall cell lung cancer (NSCLC).
      Radiosensitization may improve local tumor control when chemotherapy is given
      concurrently with hyperfractionated radiation therapy, but also may increase
      toxicity. A Phase I/II trial, Radiation Therapy Oncology Group 90-15, was
      designed to evaluate whether this strategy could improve survival with acceptable
      toxicity and be part of a Phase III trial of chemoradiation sequencing. METHODS:
      Vinblastine (5 mg/M2 weekly x 5 weeks) and cisplatin (75 mg/M2 days 1, 29, and
      50) were given during twice-daily irradiation (1.2 Gy, 6 hours apart) to 69.6 Gy
      in 58 fractions in 6 weeks. Eligible patients had American Joint Committee on
      Cancer (AJCC) Stage II (unresected) or IIIA-B NSCLC and Karnofsky performance
      status 70 or greater; there were no weight loss restrictions. RESULTS: Of 42
      eligible patients, 76% had greater than 5% weight loss, 45% had T4 primary
      tumors, and 62% were Stage IIIB. All protocol treatment was completed in 53%.
      Acute toxicity was predominantly hematologic with 19 of 42 (45%) having Grade 4
      toxicity or higher, three (7%) with septic death. Ten of 42 (24%) had Grade 3 or
      higher esophagitis. There were two (4.7%) patients with Grade 3 or higher (1 lung
      and 1 esophagus) and two (4.7%) with Grade 4 or higher (1 lung and 1 hematologic)
      late toxicities. Median survival time was 12.2 months, with an overall 1-year
      survival of 54%, an estimated 2 year survival of 28% and a 1-year progression
      free survival of 38%. CONCLUSIONS: For patients with unresectable nonsmall cell
      lung cancer, who were not selected on the basis of weight loss, concurrent
      hyperfractionated irradiation and chemotherapy had more intense acute toxicity
      than hyperfractionation alone, but late toxicity was acceptable. One and 2-year
      survival rates were 54 and 28%, respectively.

PMID- 7712446
TI  - High dose rate endobronchial brachytherapy in the management of primary and
      recurrent bronchogenic malignancies.
AB  - BACKGROUND: The clinical, radiographic, and bronchoscopic records of patients
      treated with out-patient high dose rate (HDR) endobronchial brachytherapy were
      reviewed to determine its effectiveness in patients with malignant airway
      obstruction (with or without prior external beam radiation). In addition, quality
      of life and acute and chronic morbidity were evaluated. METHODS: From January 1,
      1989 to June 30, 1993, 46 patients received 128 HDR endobronchial treatments
      employing a high activity Ir-192 source with a remote afterloader. Patients
      treated had a total of 22 primary and 17 recurrent bronchogenic carcinomas, 7 of
      which were metastatic nonpulmonary tumors. Three separate fractions of 7.0 Gy
      were prescribed to a depth of 1.0 cm. and given 1 week apart. Twelve patients
      (30%) received prior external beam irradiation (median dose, 58 Gy). RESULTS:
      Median follow-up for the entire group was 5 months (17.5 for surviving patients).
      Of the eight asymptomatic patients, five (62%) remained asymptomatic for the
      remainder of their lives. Of the 38 symptomatic patients, 28 (74%) had
      significant clinical improvement, and 12 of them remained improved for the
      duration of their lives. Of thirty-six (78%) patients examined for radiographic
      response, 25 (69%) had a partial or complete response to this treatment. In
      patients without prior irradiation, there was a tendency for a higher percentage
      of clinical and radiographic response. Two patients (4%) experienced mild,
      transient dysphagia, four patients developed self-limited radiation pneumonitis
      (9%), and three patients (7%) suffered fatal hemoptysis (all of these patients
      received prior or concurrent external beam radiotherapy). No factor (i.e., prior
      radiation therapy, number of catheters placed, surgery, or chemotherapy)
      predicted an increased risk of complications (P = NS). CONCLUSIONS: Outpatient
      HDR endobronchial brachytherapy is effective in both preventing and relieving
      endobronchial obstruction in patients with or without prior irradiation,
      recurrent lesions, or metastatic nonpulmonary disease. A significant proportion
      of patients can be rendered asymptomatic for the duration of their lives, hence
      were provided with improved quality of life. These treatments are well tolerated
      and safe, and result in minimal long term morbidity.

PMID- 7712447
TI  - Reirradiation of recurrent skin cancer of the face. A successful salvage
      modality.
AB  - BACKGROUND: The aim of this study was to assess the effectiveness of full doses
      of reirradiation to salvage previously irradiated recurrent skin cancer of the
      face. METHODS: As of December 1990, 17 patients at the Mallinckrodt Institute of
      Radiology were reirradiated for recurrent skin cancer in previously irradiated
      areas of the face. There were eight basal cell and nine squamous cell carcinomas.
      The interval between the two treatments ranged from 6 months to 15 years (median,
      4 years). The dosimetry was reviewed, and the radiation doses were recomputed by
      the biologic effective dose (BED) formula. RESULTS: The accumulated BED from the
      two irradiation regimens ranged from 48.78 to 143.5 Gy on the skin surface
      (median, 103 Gy) and 80.93 to 160.68 Gy at 5 mm depth (median, 108 Gy). Local
      control was achieved in ten patients; two of them had skin defects that required
      reconstruction. Six of seven patients with persistent tumors had squamous cell
      carcinoma. Those patients with BED of previous treatment at 5 mm depth less than
      55 Gy, and accumulated BED on skin surface of no more than 110 Gy had the best
      outcome. The residual damage of skin from previous treatment is a function of
      fraction size and total dose. CONCLUSIONS: Reirradiation is a feasible treatment
      alternative for recurrent skin cancer of the face when cosmesis is a concern.

PMID- 7712448
TI  - Postoperative radiation of free jejunal autografts in patients with advanced
      cancer of the head and neck.
AB  - BACKGROUND: Free jejunal autografts increasingly are being used to repair the
      pharynx after resections of head and neck carcinomas. Doses of greater than 45 Gy
      are generally considered to be above the tolerance of the small bowel, whereas
      the dose range for effective postoperative radiotherapy of advanced head and neck
      cancers is between 57.6 Gy and 63 Gy. Between July 1988, and December, 1992, 29
      patients at the M. D. Anderson Cancer Center were treated with a combination of
      resection of the advanced head and neck cancer, reconstruction with free jejunal
      autograft, and postoperative radiation. Planned reductions in postoperative doses
      due to the presence of the jejunum within the field were not made. This
      retrospective study analyzes the outcome of these patients with attention to
      survival, local-regional control, and complications. METHODS: Twenty-seven of the
      29 study patients had squamous cell carcinoma of the larynx or pharynx; 24 of
      these patients had Stage III or Stage IV disease. Two patients had recurrent
      papillary thyroid carcinoma. The median number of days from surgery to the start
      of radiation was 34. Radiation doses to the tumor bed ranged from 50 Gy to 72 Gy.
      The median doses to the tumor bed and the jejunal autograft were both 63 Gy.
      Surviving patients were followed from 12 to 68 months (median, 20 months) from
      the time of their surgery. RESULTS: The actuarial 2-year survival rate was 51%.
      Nine patients had local or regional recurrences above the clavicles. The 2-year
      local-regional control and freedom from relapse rates were 71 and 50%,
      respectively. The most severe complication during radiation was confluent
      mucositis in greater than 50% of the treated area, which developed in two
      patients. No patient developed a late complication related to the jejunal
      autograft. CONCLUSIONS: Postoperative radiation to free jejunal autografts used
      for pharyngeal reconstruction can be delivered safely. Doses in this setting of
      57.6 Gy to 63 Gy depending on the anticipated risk of recurrence based on
      clinical, surgical, and pathologic findings are recommended. The presence of a
      free jejunal autograft did not require a reduction of the desired doses used for
      patients with postoperatively irradiated head and neck cancer.

PMID- 7712449
TI  - Long term assessment of patterns of treatment failure and survival in patients
      with stage I or II follicular lymphoma.
AB  - BACKGROUND: Follicular lymphoma is a clearly defined type of malignant lymphoma.
      The many treatment approaches reported in the literature attest to the lack of
      agreement on its best management. The treatment experiences of patients with
      Stage I or II follicular lymphoma who were at risk for at least 5 years were
      reviewed to assess their survival, disease free survival, and patterns of
      failure. METHODS: Between 1974 and 1988, 144 patients with Stage I or II
      follicular lymphoma were treated at The University of Texas M. D. Anderson Cancer
      Center. Initial staging studies included lymphangiography in 87% of the patients,
      computerized tomography of the abdomen and pelvis in 60%, bone marrow biopsy in
      98%, and diagnostic or staging laparotomy in 33%. Forty-five patients were
      treated with regional radiotherapy, 84 patients with combined chemotherapy and
      radiotherapy, and 15 patients were treated with chemotherapy alone. RESULTS: With
      a median follow-up of 8.7 years (range, 48-182 months) the actuarial survival
      rates at 5, 10, and 15 years were 81, 69, and 63%, respectively. The freedom from
      relapse (FFR) rates were 66, 56, and 46%, respectively. The FFR rate was better
      for patients treated with chemotherapy-radiotherapy than for patients treated
      with radiotherapy alone (63 vs. 35% at 15 years). In addition, there were no
      relapses after 7.5 years in patients treated with chemotherapy-radiotherapy, but
      relapses continued even beyond 15 years in patients treated with radiotherapy
      alone. Univariate analysis for each of the treatment groups revealed age to be
      the only significant prognostic factor. There was no significant difference in
      survival or disease free survival rates for the three histologic subtypes of
      follicular lymphoma. CONCLUSION: The addition of chemotherapy to radiotherapy may
      have increased the probability of cure for patients with Stages I or II
      follicular lymphoma.

PMID- 7712452
TI  - Pregnant women in abusive relationships.

PMID- 7712451
TI  - Human papillomavirus not found in squamous and large cell lung carcinomas by
      polymerase chain reaction.

PMID- 7712450
TI  - Treatment of patients with lymphomas of the uterus or cervix with combination
      chemotherapy and radiation therapy.
AB  - BACKGROUND: Primary lymphomas of the uterus or cervix are so rare that treatment
      series of single institutions consist of very small numbers of patients, making
      standard treatment difficult to define. The outcome of patients treated with a
      combination of chemotherapy and radiation therapy was analyzed for all but
      patients with the most advanced disease. METHODS: From 1976 to 1992, 16 patients
      received definitive treatment. Thirteen patients had intact uteri (group 1) and 3
      presented with paracolpal lymphomas after previous hysterectomies (group 2).
      Twelve of the patients received chemotherapy and external irradiation. The
      remaining four underwent only chemotherapy. The overall survival and freedom from
      disease progression were analyzed according to Kaplan-Meier methods. Prognoses
      were related to the International Index, Ann Arbor stage, and International
      Federation of Gynecology and Obstetrics stage. RESULTS: Five-year survival and
      freedom from disease progression were 77% and 67%, respectively, for group 1, and
      all patients in group 2 were cured. A statistically significant correlation of
      survival with scores of the International Index was found in group 1. For
      patients with scores in the low or low-intermediate range (n = 10), 5-year
      survival was 90%. All patients who scored in the high-intermediate or high range
      (n = 3) died by 66 months after their diagnosis (P = 0.0153). The Ann Arbor stage
      had less predictive value, with 5-year survival of 89% for Stage I and II
      patients (n = 9), compared with 50% survival for the four Stage III and IV
      patients (P = 0.0701). International Federation of Gynecology and Obstetrics
      staging did not predict outcome. CONCLUSIONS: The combination of chemotherapy and
      irradiation is the most effective treatment regimen for all uterine and cervical
      lymphomas. The International Index is most predictive of outcome.

PMID- 7712453
TI  - Cytomegalovirus: no prevention, no cure.

PMID- 7712454
TI  - Breaking the barriers to nursing research.

PMID- 7712455
TI  - Hospital research comes of age.

PMID- 7712456
TI  - [The elderly and drug abuse].
AB  - LESA is a program of Lifestyle Enrichment for Senior Adults experiencing problems
      associated with their use of alcohol and other psychoactive drugs. It includes a
      direct service and a community education component. The treatment approach
      incorporates knowledge about the normal aging process, drug dependency, and
      holistic health, along with interventions from addiction treatment centres,
      holistic care, nursing and social work. The overall goal of the program is to
      improve the physical, psychosocial, spiritual, and environmental health of
      seniors who are living independently in the community and experiencing problems.
      To be admitted to this program, clients must be residents of Ottawa-Carleton who
      are 55 years of age or older; live independently; use psychoactive drugs in a
      manner presumed, or confirmed, to be hazardous; and express the desire for
      improved health or well-being. This article, based on documents available in both
      French and English, presents the special features of the program and its
      philosophy. Problematic drug use has four basic, interactive elements: the
      person(s) who uses the drug(s); the reasons for use; the drug(s) used; and the
      consequence of use. Effective intervention takes all of these elements into
      account. Early onset, intermittent problems, and late onset problem users, all
      have a reason for use. The positive and negative consequences of drug use, and
      the implications for seniors and for the rest of the population, are explained.

PMID- 7712457
TI  - From a patient's perspective.

PMID- 7712459
TI  - Cradle chat.

PMID- 7712458
TI  - Research and you.

PMID- 7712461
TI  - Frequent loss of heterozygosity at the retinoblastoma susceptibility gene (RB)
      locus in aggressive pituitary tumors: evidence for a chromosome 13 tumor
      suppressor gene other than RB.
AB  - Mice bearing retinoblastoma susceptibility gene (RB) germ-line mutations almost
      invariably develop pituitary neoplasms. We therefore tested 17 patients with
      pituitary tumors for loss of heterozygosity (LOH) using an RB sequence
      polymorphism and 5 polymorphic microsatellite markers surrounding the RB gene on
      the long arm of chromosome 13. In all of the 13 malignant or highly invasive
      pituitary tumor cases, and in 4 of their respective metastases, a RB allele was
      lost. In contrast, no LOH at the RB locus was detected in 4 benign pituitary
      adenoma cases. Three invasive tumors also lost a portion of 13q, which included
      D13s137, D13s133, and D13s118 telomeric and centromeric to RB, respectively.
      Immunohistochemical analysis, however, revealed the presence of RB protein in
      tumors with LOH and the RB locus. Therefore, although inactivation of RB may play
      a role in the development of invasive pituitary adenomas and carcinomas in mice,
      another tumor suppressor gene on 13q is likely involved in human pituitary tumor
      progression. LOH of 13q markers may also be of predictive value in determining
      the biological behavior of pituitary macroadenomas and their progression to
      invasiveness and frank malignancy.

PMID- 7712460
TI  - Association of rat p15INK4B/p16INK4 deletions with monosomy 5 in kidney
      epithelial cell lines but not primary renal tumors.
AB  - Recently the putative tumor suppressor gene p16INK4 was mapped to human
      chromosome 9p21, which is homologous to rat chromosome 5. Monosomy of rat
      chromosome 5 occurs with high frequency in rat kidney tumor-derived cell lines
      (ERC lines). Thus, we studied these lines in order to investigate the involvement
      of p15INK4B and p16INK4 in the genesis of this tumor type. p15INK4B and p16INK4
      were found by Southern blot analysis to be codeleted in five of seven of these
      lines. This was confirmed by Northern blot analysis with a probe for the rat
      p15INK4B gene. In normal rat tissues, expression of p15INK4B was abundant in lung
      (2.5 and 2.0 kilobases), less abundant in testis (2.5, 2.0, 1.1, and 0.9
      kilobases), barely detectable in liver (2.0 kilobases), and not detectable in
      neonatal kidney, adult kidney, brain, heart, or spleen. In the ERC lines,
      p15INK4B was expressed as a single 2.0-kilobase transcript observed only in those
      cell lines in which the gene was detected by Southern blot analysis. However,
      neither p15INK4B nor p16INK4 were deleted in 12 of 12 primary kidney tumors
      examined, suggesting that deletion of these genes is not directly involved in the
      process of renal tumor development but may be related to tumor progression or
      autonomous growth in vitro. A panel of rat kidney epithelial cell lines
      chemically transformed in vitro (TRKE lines) that had high-frequency monosomy 5
      were also examined, but deletion of p15INK4B and p16INK4 was observed in only one
      of six of the TRKE lines. To our knowledge, this is the first reported
      investigation of these genes in rodent tumors and cell lines, and its data
      support the theory that alterations of genes located in the INF region of rat
      chromosome 5 may play a role in rodent cell transformation.

PMID- 7712462
TI  - A novel cancer therapy based on oxygen radicals.
AB  - The antitumor effect of oxygen radicals produced by hypoxanthine and xanthine
      oxidase reaction was studied in an experimental rabbit model. VX2 carcinomas were
      transplanted into rabbit hind legs. Hypoxanthine was administered continuously
      through the ear vein, while xanthine oxidase was administered simultaneously
      through the femoral artery. As a result, hypoxanthine and xanthine oxidase
      reacted only in the hind leg, and superoxide was produced in that area. The
      volume of the VX2 carcinoma was measured immediately prior to treatment and 7
      days later. As an index of lipid peroxidation, thiobarbituric acid-reactive
      substances in the tumor tissue were measured 60 min following infusion of
      hypoxanthine and xanthine oxidase. Tumor growth was suppressed significantly by
      the hypoxanthine-xanthine oxidase reaction, and thiobarbituric acid-reactive
      substances in the tumor tissue infused with hypoxanthine and xanthine oxidase
      were significantly increased. In addition, the antitumor effect of the
      hypoxanthine and xanthine oxidase reaction was significantly inhibited by the
      administration of superoxide dismutase and catalase. Pathological examination
      showed that oxygen radicals produced by hypoxanthine and xanthine oxidase
      reaction were selectively more destructive for VX2 carcinoma tissue than muscle
      tissue surrounding the tumor region. These results suggest that oxygen radicals
      produced by hypoxanthine and xanthine oxidase reaction produce an anticancer
      effect and that the VX2 carcinoma used in this study was more sensitive to oxygen
      radicals than normal muscle tissue.

PMID- 7712463
TI  - Prevalence of androgen receptor gene mutations in latent prostatic carcinomas
      from Japanese men.
AB  - The incidence rate of clinically apparent prostatic carcinoma is 8-fold higher in
      the United States than in Japan, while the prevalence of latent prostatic
      carcinoma, a presumed precursor to clinical carcinoma, is similar in the two
      countries. The purpose of this study was to investigate the hypothesis that this
      profound difference in incidence rates of clinical carcinoma reflects distinct
      profiles of molecular genetic alterations in the latent precursor lesions that
      occur in the two countries. A significant fraction of latent carcinomas from
      Japanese men were found to contain inactivating mutations of the androgen
      receptor gene, while no such mutations were found in latent carcinomas from
      American men. No mutations were found in clinical carcinomas from either country.
      These data offer a potential molecular genetic explanation that may partially
      account for the distinct prostatic carcinoma incidence rates in these two
      populations.

PMID- 7712464
TI  - ALL-1 gene rearrangements in acute myeloid leukemia: association with M4-M5
      French-American-British classification subtypes and young age.
AB  - We have analyzed by Southern blotting the ALL-1 (MLL, HRX, Hrtx 1) gene
      configuration in a series of 126 patients with acute myeloid leukemia (AML)
      representative of all ages and French-American-British Classification groups and
      correlated this genetic feature with clinical and biological features at
      diagnosis. ALL-1 gene rearrangements were detected in 17 of the 74 cases with M4
      M5 (myelomonocytic and monocytic) AML and in 2 of the 52 cases with other
      leukemic subtypes (P < 0.01). Within the series of 74 M4-M5 patients, ALL-1
      rearrangements were significantly associated with French-American-British
      Classification M5 (P = 0.009), high WBC (P = 0.002), and young age. In
      particular, all 5 infant (< 1.5 years) AML cases, 6 of the 19 (31%) patients
      between 1.5 and 18 years of age, and 6 of the 50 (12%) patients > 18 years old
      showed an altered ALL-1 genomic configuration (P < 0.001). Immunophenotypic
      characterization revealed coexpression of lymphoid and myeloid markers in 6 of 17
      ALL-1 rearranged M4-M5 cases. The IgH gene configuration was studied in 77 of 126
      AMLs. Five patients (6%) showed IgH clonal rearrangements and all were in the ALL
      1 rearranged group (P < 0.0001). Our findings indicate that ALL-1 rearrangement
      is the commonest genetic alteration presently detectable in M4-M5 AML,
      particularly in childhood where it is found in up to one-third of all cases. The
      association of IgH rearrangements with ALL-1 alterations in AML, coupled to the
      frequent detection in this subset of lymphoid associated markers, further
      supports the origin of these tumors from a common multipotent precursor with
      bipotential lymphoid and monocytic differentiation capability.

PMID- 7712465
TI  - Tissue factor-initiated thrombin generation activates the signaling thrombin
      receptor on malignant melanoma cells.
AB  - The human melanoma cell line M24met expresses tissue factor, the cellular
      initiator of the blood coagulation cascade. Blocking of the coagulation pathways
      at the level of tissue factor, factor Xa, or thrombin inhibits hematogenous
      M24met metastasis in SCID mice, implicating a role for thrombin generation in
      this process. Dependent on cell surface tissue factor activity, M24met cells
      generate thrombin in vitro. Thrombin and the thrombin receptor agonist peptide
      TRP-14 activate a signaling pathway in M24met cells that involves an increase in
      intracellular calcium and induces cell proliferation. Immunofluorescence
      evidences expression of the signaling thrombin receptor on these cells. Thus,
      M24met melanoma cells express both the initiating cell surface receptor for the
      coagulation pathways and the central signaling receptor of the coagulation
      system, suggesting the in situ generation of proliferative signals which can
      contribute to the malignant phenotype.

PMID- 7712466
TI  - Relationship of multidrug resistance to rhodamine-123 selectivity between
      carcinoma and normal epithelial cells: taxol and vinblastine modulate drug
      efflux.
AB  - Preferential retention and cytotoxicity of Rhodamine-123 (Rho-123) was originally
      reported in a number of carcinoma cell types isolated from a variety of tissues
      as compared to normal epithelial cells from a limited number of other tissues. In
      the present study, we have examined Rho-123 selectivity in normal and tumor cell
      lines isolated from the same tissue source, i.e., human breast. We found that:
      (a) in matched pairs of normal and carcinoma breast cells, Rho-123 displays no
      preferential retention in either cell type; (b) there is no preferential toxicity
      in carcinoma as compared to normal breast cells; in fact, one of the carcinoma
      cell lines (MDA-MB231) shows moderate resistance to this dye; (c) all of the
      human breast cell lines do not express P-glycoprotein-mediated multidrug
      resistance; (d) the normal monkey kidney epithelial cell line CV-1, which was
      originally used as a model to demonstrate the relative resistance of normal
      epithelial cells to this drug, is found to express high levels of the mdr-1 gene,
      is resistant to other multidrug-resistant drugs (taxol and vinblastine), and its
      resistance to Rho-123 as well as decreased Rho-123 retention can be reversed by
      verapamil; and (e) taxol and vinblastine are found to block increased Rho-123
      efflux in CV-1 cells. Thus, overall the data suggest that preferential retention
      and cytotoxicity of Rho-123 in carcinoma versus normal epithelial cells is
      related to the differential expression of the mdr-1 gene.

PMID- 7712467
TI  - Abrogation of the G2 checkpoint results in differential radiosensitization of G1
      checkpoint-deficient and G1 checkpoint-competent cells.
AB  - We have examined the effect of abrogation of the G2 checkpoint on the
      radiosensitivity of G1 checkpoint-proficient and G1 checkpoint-deficient cells.
      A549 human lung adenocarcinoma cells were transduced with the E6 oncogene of the
      human papillomavirus type 16 to eliminate their radiation-induced G1 arrest.
      These E6+ cells exhibited a dose-dependent increase in radiation resistance
      compared to control A549 cells transduced with the vector alone. Treatment (96 h)
      with 2 mM caffeine resulted in an abrogation of the cellular G2 checkpoint in
      both E6+ and control cells and a differential radiosensitizing effect on the two
      cell lines such that the E6+ clones and the vector controls became equally
      radiosensitive. These data show that human tumors which are radioresistant due to
      the loss of the p53-mediated G1 checkpoint can be made radiosensitive by
      abrogation of the G2 checkpoint. The implications of these results for cancer
      therapy are discussed.

PMID- 7712468
TI  - Differential sensitivity of p53(-) and p53(+) cells to caffeine-induced
      radiosensitization and override of G2 delay.
AB  - Most drug discovery efforts have focused on finding new DNA-damaging agents to
      kill tumor cells preferentially. An alternative approach is to find ways to
      increase tumor-specific killing by modifying tumor-specific responses to that
      damage. In this report, we ask whether cells lacking the G1-S arrest in response
      to X-rays are more sensitive to X-ray damage when treated with agents that
      override G2-M arrest. Mouse embryonic fibroblasts genetically matched to be (+)
      or (-) p53 and rat embryonic fibroblasts (+) or (-) for wild-type p53 function
      were irradiated with and without caffeine, a known checkpoint inhibitor. At low
      doses (500 microM), caffeine caused selective radiosensitization in the p53(-)
      cells. At this low dose (where no effect was seen in p53(+) cells), the p53(-)
      cells showed a 50% reduction in the size of the G2-M arrest. At higher doses (2
      mM caffeine), where sensitization was seen in both p53(+) and p53(-) cells, the
      radiosensitization and the G2-M override were more pronounced in the p53(-)
      cells. The greater caffeine-induced radiosensitization in p53(-) cells suggests
      that p53, already shown to control the G1-S checkpoint, may also influence
      aspects of G2-M arrest. These data indicate an opportunity for therapeutic gain
      by combining DNA-damaging agents with compounds that disrupt G2-M arrest in
      tumors lacking functional p53.

PMID- 7712469
TI  - Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and
      pentoxifylline.
AB  - The possibility that appropriately designed chemotherapy could act selectively
      against p53-defective tumor cells was explored in MCF-7 human breast cancer
      cells. These cells were chosen because they have normal p53 function but are
      representative of a tumor cell type that does not readily undergo p53-dependent
      apoptosis. Two sublines (MCF-7/E6 and MCF-7/mu-p53) were established in which p53
      function was disrupted by transfection with either the human papillomavirus type
      16 E6 gene or a dominant-negative mutant p53 gene. p53 function in MCF-7/E6 and
      MCF-7/mu-p53 cells was defective relative to control cells in that there were no
      increases in p53 or p21Waf1/Cip1 protein levels and no G1 arrest following
      exposure to ionizing radiation. Survival assays showed that p53 disruption
      sensitized MCF-7 cells to cisplatin (CDDP) but not to several other DNA-damaging
      agents. CDDP sensitization was not limited to MCF-7 cells since p53 disruption in
      human colon carcinoma RKO cells also enhanced sensitivity to CDDP. Contrary to
      the other DNA-damaging agents tested, CDDP-induced DNA lesions are repaired
      extensively by nucleotide excision, and in agreement with a defect in this
      process, MCF-7/E6 and MCF-7/mu-p53 cells exhibited a reduced ability to repair a
      CDDP-damaged chloramphenicol acetyltransferase-reporter plasmid transfected into
      the cells. Therefore, we attributed the increased CDDP sensitivity of MCF-7 cells
      with disrupted p53 to defects in G1 checkpoint control, nucleotide excision
      repair, or both. The G2 checkpoint inhibitor pentoxifylline exhibited synergism
      with CDDP in killing MCF-7/E6 cells but did not affect sensitivity of the control
      cells. Moreover, pentoxifylline inhibited G2 checkpoint function to a greater
      extent in MCF-7/E6 than in the parental cells. These results suggested that, in
      the absence of p53 function, cancer cells are more vulnerable to G2 checkpoint
      abrogators. Our results show that a combination of CDDP and pentoxifylline is
      capable of synergistic and preferential killing of p53-defective tumor cells that
      do not readily undergo apoptosis.

PMID- 7712470
TI  - Repression of protein kinase C and stimulation of cyclic AMP response elements by
      fumonisin, a fungal encoded toxin which is a carcinogen.
AB  - Fusarium moniliforme (FM) is a major fungal pathogen of corn and is involved with
      stalk rot disease. FM is widely spread throughout the world, including the United
      States. Most strains of FM produce several mycotoxins, the most prominent of
      which is called fumonisin. Recent epidemiological studies indicated that
      ingestion of fumonisin correlates with a higher incidence of esophageal cancer in
      Southern and Northern Africa and China. Furthermore, fumonisin causes a
      neurodegenerative disease in horses, induces hepatic cancer in rats, and induces
      pulmonary edema in swine. Considering that high levels of fumonisin have been
      detected in healthy and diseased corn grown in the United States, fumonisin may
      pose a health threat to humans and livestock animals. Structurally, fumonisin
      resembles sphingolipids which are present in the membranes of animal and plant
      cells. At the present time, very little is known concerning the mechanism by
      which fumonisin elicits its carcinogenic effect. Our studies indicate that
      fumonisin represses expression of protein kinase C and AP-1-dependent
      transcription. In contrast, fumonisin stimulated a simple promoter containing a
      single cyclic AMP response element. Since fumonisin did not alter protein kinase
      A activity, it appears that cyclic AMP response element activation was
      independent of protein kinase A. It is hypothesized that the ability of fumonisin
      to alter signal transduction pathways plays a role in carcinogenesis.

PMID- 7712471
TI  - Use of the stress-inducible grp78/BiP promoter in targeting high level gene
      expression in fibrosarcoma in vivo.
AB  - Current advances in human gene therapy open up new frontiers for molecular
      therapies of cancer. However, one major limitation in cancer gene therapy is the
      lack of a general tumor-specific promoter which allows stringent and high level
      expression of the therapeutic reagent in malignantly transformed but not normal
      tissues. Hallmark features of solid tumors such as glucose deprivation, chronic
      anoxia, and acidic pH induce the glucose-regulated proteins, in particular,
      GRP78/BiP, a M(r) 78,000 endoplasmic reticulum-localized protein with chaperone
      and calcium-binding properties. We report here that a truncated rat grp78
      promoter with most of the distal basal elements removed can be utilized as a
      potent internal promoter in a retroviral vector to drive high level expression of
      a reporter gene in a murine fibrosarcoma model system. The stress-inducible grp78
      promoter offers a novel approach for gene delivery systems targeting
      transcription in tumorigenic cells.

PMID- 7712472
TI  - Effect of estrogen withdrawal on energy-rich phosphates and prediction of
      estrogen dependence monitored by in vivo 31P magnetic resonance spectroscopy of
      four human breast cancer xenografts.
AB  - The effect of estrogen withdrawal on energy metabolism was studied in four human
      breast cancer xenografts: the estrogen-dependent MCF-7 and ZR75-1 and the
      estrogen-independent ZR75/LCC-3 and MDA-MB-231. The tumors were grown in
      ovariectomized nude mice with a s.c. implanted estrogen pellet. After Gompertzian
      growth was verified, the estrogen pellet was removed from half of the animals. In
      vivo 31P magnetic resonance spectroscopy of the tumors was performed 1 day before
      and on days 2, 6, and 14 after estrogen removal. Estrogen withdrawal induced a
      significant increase in the nucleoside triphosphate:Pi ratio in the two estrogen
      dependent xenografts, whereas this ratio remained unchanged in the estrogen
      independent tumors. In ZR75/LCC-3 tumors a slight decrease in nucleoside
      triphosphate:Pi was observed following onset of estrogen stimulation after
      initial growth without estrogen. Extracts of freeze-clamped tumors prepared 14
      days after estrogen removal were analyzed for ATP and phosphocreatine content.
      Our findings suggest a correlation between estrogen withdrawal and the steady
      state concentrations of ATP, phosphocreatine, and Pi in human breast cancer
      xenografts. Discrimination analysis of the pretherapeutic spectra enabled us to
      identify the tumor line and the estrogen dependence of the tumors in 80-90% of
      all cases.

PMID- 7712473
TI  - Quantitation of 6-thioguanine residues in peripheral blood leukocyte DNA obtained
      from patients receiving 6-mercaptopurine-based maintenance therapy.
AB  - The antimetabolite 6-mercaptopurine is widely utilized in maintenance therapy for
      childhood acute lymphoblastic leukemia. Following p.o. administration, this
      prodrug undergoes extensive biotransformation, resulting in the generation of a
      plethora of metabolites including 2'-deoxy-6-thioguanosine triphosphate.
      Incorporation of 6-thioguanine (6-TG) bases into DNA is generally considered to
      be central to thiopurine-mediated cytotoxicity. We have developed a novel
      precolumn derivatization HPLC technique for quantifying 6-TG base accumulation
      into leukocyte DNA obtained from acute lymphoblastic leukemia patients receiving
      6-mercaptopurine maintenance therapy. The method is based on enzymatic
      degradation of DNA to 2'-deoxyribonucleosides and the derivatization of released
      2'-deoxy-6-thioguanosine with a thiol-reactive reagent containing a 7-amino-4
      methylcoumarin-3-acetic acid fluorophore. The 2'-deoxy-6-thioguanosine-7-amino-4
      methylcoumarin-3-acetic acid adduct is resolved by reversed-phase HPLC and
      quantified fluorometrically. Assay response is linear from 15 pmol to 60 fmol 6
      TG bases/microgram DNA with a limit of quantitation corresponding to the
      incorporation of 1 6-TG residue per 50,000 bases. In a small cohort of acute
      lymphoblastic leukemia patients receiving p.o. 6-mercaptopurine-based maintenance
      therapy, significant interindividual variation in the accumulation of 6-TG bases
      into leukocyte DNA was revealed. The determined levels of drug base incorporation
      ranged from 95 to 710 fmol 6-TG bases/microgram DNA (6-TG base:nucleotide ratio
      1:32,000 to 1:4,000). The assay may provide a novel methodology for
      pharmacological monitoring of thiopurine therapy either in the routine clinical
      setting or during studies of alternative routes of drug delivery.

PMID- 7712474
TI  - Expression of Sia alpha 2-->6Gal beta 1-->4GlcNAc residues on sugar chains of
      glycoproteins including carcinoembryonic antigens in human colon adenocarcinoma:
      applications of Trichosanthes japonica agglutinin I for early diagnosis.
AB  - The N-linked sugar chain structures of the carcinoembryonic antigen (CEA)
      produced by liver metastases of colon cancers and the normal counterpart of CEA
      purified from human adult feces (NFA-2) were previously determined comparatively
      (K. Fukushima, T. Ohkura, M. Kanai, M. Kuroki, Y. Matsuoka, A. Kobata, and K.
      Yamashita. Glycobiology, 5:105-115, 1995). Seventy-five % of NFA-2 contained
      complex type sugar chains with Gal beta 1-->3GlcNAc residues, in contrast to the
      sugar chains of CEA, in which over 90% of the oligosaccharides contained Gal beta
      1-->4GlcNAc residues, and Sia alpha 2-->6Gal beta 1-->4GlcNAc residues were
      detected in 18 to 65% of the oligosaccharides. The expression of Sia alpha 2-
      >6Gal beta 1-->4GlcNAc residues on CEA molecules in sera and tissues was
      investigated using Trichosanthes japonica agglutinin I (TJA-I), which interacts
      with Sia alpha 2-->6Gal beta 1-->4 GlcNAc residues. Ten purified CEA samples
      bound to a TJA-I column while seven NFA-2 samples passed through the column.
      Various concentrations of serum CEA samples from patients with metastatic colon
      cancers exclusively bound to the TJA-I column, reflecting that CEA molecules
      exfoliated into the blood circulation comprise sugar chains with Sia alpha 2-
      >6Gal beta 1-->4GlcNAc residues. In histochemical studies involving biotinylated
      TJA-I, normal mucosa (n = 20) and benign adenomas (n = 20) were not stained, and
      83% of well and moderately differentiated colon adenocarcinomas (n = 53) reacted
      with TJA-I, although poorly differentiated ones (n = 9) and mucinous specimens (n
      = 10) were negative. Because over 90% of colon adenocarcinomas can be
      differentiated, TJA-I staining might be applicable to the early diagnosis of
      colon cancers.

PMID- 7712475
TI  - Role of ornithine decarboxylase in epidermal tumorigenesis.
AB  - Ornithine decarboxylase (ODC) plays a key role in the biosynthesis of polyamines,
      which are necessary for cell growth and differentiation. ODC expression is very
      tightly controlled in all normal cells; however, regulation of its expression is
      altered in many tumor cells resulting in much higher basal levels of ODC in
      tumors. To investigate the potential role of ODC overexpression in epidermal
      tumorigenesis, we constructed a replication-defective retroviral vector to
      overexpress a truncated ODC protein in epidermal cells. Stable viral infection of
      mouse epidermal cells dramatically increases not only the basal ODC activity but
      also the basal putrescine and spermidine levels. In all infected epidermal cells
      with high polyamine levels, DNA synthesis is increased as measured by
      [3H]thymidine incorporation into DNA as well as increased bromodeoxyuridine
      staining in the nuclei of ODC-infected epidermal cells. ODC viral infection of
      nontumorigenic BK-1 epidermal cells and primary cultures of mouse keratinocytes
      and fibroblasts from newborn mouse skin yields no tumors when injected s.c. into
      athymic nude mice or when transplanted as skin grafts onto nude mice. Epidermal
      cell lines SP-1 and 308 (which possess an activated rasHa gene) are not
      tumorigenic when injected s.c. into nude mice. However, following infection with
      the ODC virus, they form tumors filled with keratin and papilloma-like
      projections of hyperplastic epidermal cells displaying dysplasia and many mitotic
      figures. These data indicate that ODC overexpression by itself is not sufficient
      to induce tumors in normal cells but that increased expression of ODC enhances
      tumor development in initiated premalignant epidermal cells.

PMID- 7712476
TI  - DNA damage in cyclophosphamide-resistant tumor cells: the role of glutathione.
AB  - The relationship between DNA damage removal and cellular sensitivity to the
      alkylating agent cyclophosphamide (CP), currently one of the most effective drugs
      in the treatment of human tumors, has not been well established. In the present
      study, we have analyzed drug-induced DNA cross-link persistence in the CP
      resistant subline KHT-rep/iv and its sensitive counterpart KHT-iv. The alkaline
      elution technique was used to detect both DNA-DNA and DNA-protein cross-links
      formed following exposure to clinically achievable CP concentrations. In
      addition, the role of glutathione (GSH) in the cross-link persistence was
      analyzed. The KHT-rep/iv cell line was chosen for study because compared to the
      parent KHT-iv line, this cell line demonstrates 2-3-fold increased GSH levels,
      and resistance to CP is known to be mediated by thiols. Following exposure to 4
      hydroperoxy-cyclophosphamide (4-OOHCP), an active form of CP, the KHT-rep/iv
      cells exhibited fewer total cross-links and a shift in the time of maximal cross
      link formation (6.2 at 2 h versus 2.9 at 4 h for the parent and resistant lines,
      respectively). When the GSH content of the resistant cells was reduced to equal
      that of the parent cell line prior to the alkaline elution assay, both the total
      number and time course of development of cross-links were similar between the two
      lines. Also, when the cells were exposed to mechlorethamine, an alkylating agent
      which forms cross-links at a much faster rate than 4-OOHCP, the time course of
      cross-link formation after mechlorethamine exposure was similar between the two
      sublines, with maximal cross-link formation occurring after a 1-h incubation. The
      present findings suggest that (a) the increased GSH levels in KHT-rcp/iv cells
      may be responsible for the delay in maximal cross-link development after
      treatment with 4-OOHCP, possibly by binding with the monoadduct produced by the
      drug; and (b) the faster reaction rate of mechlorethamine cross-link formation
      may prevent the tripeptide from binding to the monoadduct. These results are
      consistent with the hypothesis that GSH may "quench" the formation of cross-links
      following 4-OOHCP exposure.

PMID- 7712477
TI  - Salicylic acid inhibits ultraviolet- and cis-platinum-induced human
      immunodeficiency virus expression.
AB  - Previous studies have shown that exposure of HeLa cells stably transfected with
      an HIV-long terminal repeat-chloramphenicol acetyltransferase (HIV-LTR-CAT)
      construct to many DNA-damaging agents (such as UV light) induces expression from
      the HIV LTR. By culturing the cells with salicylic acid we demonstrated dose
      dependent repression of this UV-or cis-platinum (cis-Pt)-induced HIV expression.
      While salicylic acid treatment, indomethacin treatment, UV exposure, or cis-Pt
      treatment alone decreased viability by up to 50%, equal numbers of viable cells
      were used for the CAT assays. Repression was evident if salicylic acid was
      administered 2 h before, at the same time as, or up to 6 h after exposure to the
      DNA-damaging agent. The kinetics were similar for UV- and for cis-Pt-induced HIV
      expression, and induction was dependent on the UV dose or cis-Pt concentration
      added to the culture. pH changes of the media alone in the absence of salicylic
      acid did not affect HIV expression. Indomethacin (100 microM) did not affect UV-
      or cis-Pt-induced HIV expression. These results suggest a role for the
      prostaglandins or the cyclo-oxygenase pathway or both in HIV induction mediated
      by DNA-damaging agents.

PMID- 7712478
TI  - The role of human glutathione S-transferase isoenzymes in the formation of
      glutathione conjugates of the alkylating cytostatic drug thiotepa.
AB  - Nonenzymatic and glutathione S-transferase (GST) catalyzed glutathione (GSH)
      conjugation has been postulated as a mechanism by which alkylating cytostatic
      drugs can be inactivated intracellularly. In this study, we describe studies on
      the glutathione-dependent biotransformation of thiotepa (tris(1
      aziridinyl)phosphine sulfide), a trifunctional alkylating agent. 31P NMR studies
      showed that thiotepa is stable in 0.07 M phosphate buffer, pH 7.4 (t1/2 = 3300
      min). In the presence of glutathione, the rate of disappearance of thiotepa
      increased greatly (t1/2 = 282 min). Both monoglutathionyl thiotepa and
      diglutathionyl thiotepa conjugates were identified by 31P NMR and mass
      spectrometry. Addition of GST A1-1 (alpha) to an incubation of thiotepa and GSH
      further increased the rate of disappearance of thiotepa (t1/2 = 100 min) and
      increased the rate of formation of monoglutathionyl thiotepa. The rate of
      formation of diglutathionyl thiotepa was not altered, suggesting that the
      formation of diglutathionyl thiotepa is not catalyzed by GST A1-1. The role of
      purified human GST on the formation of monoglutathionyl thiotepa was further
      studied by HPLC. In incubations with 0.2 mM thiotepa, 1 mM GSH, and 40 microM
      GST, both GST A1-1 and P1-1 enhanced the formation of the monoglutathionyl
      conjugate 30-35-fold above the nonenzymatic formation, while GST A2-2 and M1a-1a
      did not catalyze the rate of formation of this conjugate. Kms for the GST A1-1
      (alpha) and P1-1 (pi) catalyzed formation of monoglutathionyl thiotepa were in
      the 5-7 mM range. Since the pH in tumors might be lower than in normal cells, the
      pH dependency of the GST P1-1 catalyzed formation of monoglutathionyl thiotepa
      was also studied. At all pHs tested (range, 5.5-8.5), a marked catalytic effect
      of both GST P1-1 and A1-1 on the formation of monoglutathionyl conjugates was
      noted. The role of GST on the formation of monoglutathionyl conjugates of tepa
      (tris(1-aziridinyl)phosphine oxide), the major metabolite formed from thiotepa,
      was also studied. Both GST A1-1 and P1-1 could enhance the formation of the
      glutathione conjugate 37-46-fold above the spontaneous levels, while GST M1a-1a
      and A2-2 again did not increase the rate of formation of this conjugate. The
      results of these studies show that the aziridine moieties in thiotepa/tepa are
      substrates for both GST A1-1 and P1-1. Thus, GST catalyzed glutathione
      conjugation of thiotepa might be an important factor in the development of drug
      resistance towards thiotepa.

PMID- 7712479
TI  - Alterations in the topoisomerase II alpha gene, messenger RNA, and subcellular
      protein distribution as well as reduced expression of the DNA topoisomerase II
      beta enzyme in a mitoxantrone-resistant HL-60 human leukemia cell line.
AB  - A human HL-60 leukemia cell line selected for resistance to mitoxantrone, HL
      60/MX2, displays cross-resistance only to agents whose cytotoxicities result from
      interaction with the nuclear enzyme DNA topoisomerase II (topo II). The topo II
      catalytic activity is reduced 2-fold in the drug-resistant cell line in
      association with the absence of the M(r) 180,000 isoform of topo II and the
      finding of novel M(r) 160,000 topo II alpha-related immunoreactive protein in
      these cells by immunoblot. The topo II alpha (M(r) 170,000) protein levels in
      nuclear extracts from the HL-60/MX2 cells were noted on average to be
      approximately 40% lower than in comparable HL-60 nuclei. Studies of the
      subcellular localization of topo II by immunohistochemical and fractional
      extraction techniques demonstrated that the M(r) 160,000 topo II alpha-related
      protein is primarily localized in the cytoplasm. Levels of the 6.3-kilobase topo
      II alpha mRNA were noted to be reduced 2-fold in the HL-60/MX2 cells in
      association with the finding of a novel 4.8-kilobase topo II alpha-related mRNA
      transcript that was present in HL-60/MX2 but not HL-60 cells. The absence of topo
      II beta protein in nuclear and whole cell extracts from the HL-60/MX2 cells was
      associated with the virtual absence of detectable topo II beta mRNA in those
      cells by Northern blot analysis. Using a reverse transcription-PCR assay we were
      able to demonstrate the presence of very low levels of topo II beta mRNA in HL
      60/MX2 cells, representing < 1% of that found in the HL-60 cells. In contrast,
      the nuclear catalytic activity and cellular mRNA levels of the related nuclear
      enzyme DNA topoisomerase I were nearly identical in the two cell types. Southern
      blot analysis of DNA extracted from the drug-sensitive and drug-resistant cells
      revealed a structural alteration in one topo II alpha allele in the HL-60/MX2
      cells, but there was no evidence of rearrangement or hypermethylation of the topo
      II beta locus. These results indicate that the reduced levels of topo II alpha
      and beta isoenzymes observed in mitoxantrone-resistant HL-60/MX2 cells are
      related to changes in the levels of their respective mRNA transcripts. The
      identification of structural changes in one topo II alpha allele in the HL-60/MX2
      cell line suggests that the altered allele may serve as the source of the unique
      4.8-kilobase topo II alpha-related mRNA transcript and the M(r) 160,000 protein
      discovered in those cells.

PMID- 7712480
TI  - Anti-BA46 monoclonal antibody Mc3: humanization using a novel positional
      consensus and in vivo and in vitro characterization.
AB  - Mc3 is a murine mAb that is highly effective in treating breast tumors in
      experimental radioimmunotherapy. Mc3 binds to BA46, a 46-kDa glycoprotein of the
      human milk fat globule membrane that is also expressed in breast carcinoma cells.
      We cloned and sequenced cDNAs encoding the variable regions of Mc3 and
      constructed an IgG1, kappa human/mouse chimeric antibody. We then humanized the
      variable regions of Mc3 using a positional consensus method and retaining
      residues that might either contact the complementarity-determining regions or the
      opposite chain. This positional consensus is novel in that it does not include
      residues with buried side chains. Humanized Mc3 retained full binding affinity,
      and fully competes with murine Mc3 for antigen binding. Humanized and murine 131I
      labeled Mc3 behaved identically in athymic nu/nu mice biodistribution studies.
      The tumor uptake levels for both antibodies increased over a period of 4 days
      within a range of 13-20% of the injected dose per g with extremely favorable
      tumor:normal ratios. Also, a single therapeutic dose of 131I-labeled humanized
      Mc3 in the same animal model reduced the average tumor size and produced one of
      five cures while in the uninjected control tumor growth continued unabated. We
      believe that these results justify the implementation of Phase I human clinical
      trials for imaging and radioimmunotherapy of breast cancer.

PMID- 7712481
TI  - Effectiveness of delta-aminolevulinic acid-induced protoporphyrin as a
      photosensitizer for photodynamic therapy in vivo.
AB  - We examined the effectiveness of systemic administration of delta-aminolevulinic
      acid (delta-ALA) to induce endogenous protoporphyrin as a regimen for use in
      photodynamic therapy (PDT) of transplanted R3230AC rat mammary adenocarcinomas in
      vivo. Levels of porphyrins synthesized in various tissues after systemic
      administration of delta-ALA differed, with their accumulation in tumor tissue
      being dependent on both the dose and the time after delta-ALA administration.
      Tumor, liver, and intestine contained greater than 3.0 micrograms porphyrin/g
      tissue at 3 h after delta-ALA injection, whereas porphyrin levels in rat skin and
      muscle at that time were an order of magnitude lower. Analysis of tissue by HPLC
      revealed that the predominant porphyrin synthesized in tumors was protoporphyrin
      IX, whereas in liver, 18% of the total porphyrin detected was protoporphyrin IX,
      and in muscle, it was undetectable. Time-dependent studies of the uptake of 14C
      label from delta-ALA into the various tissues were not predictive of either the
      total amount of porphyrin or which porphyrin species would be present at 3 h
      after delta-ALA injection. Additionally, no simple relationship was apparent
      between the activities of certain selected enzymes involved in heme biosynthesis
      and the concentrations of porphyrins in the different tissues. High levels of
      tumor protoporphyrin IX were sustained by administration of two sequential doses
      of delta-ALA, at 3.0 and 1.5 h prior to irradiation. Using these treatment
      conditions, we inhibited R3230AC growth to an extent that was comparable to that
      obtained for Photofrin-induced PDT. High energy phosphate metabolism, measured by
      nuclear magnetic resonance spectroscopy in vivo, was dramatically impaired after
      delta-ALA-based PDT, with tumor ATP levels reduced to near zero by 4 h after
      irradiation. Our results demonstrated that delta-ALA-based PDT may be an
      alternative to current treatment protocols that use exogenously administered
      photosensitizers.

PMID- 7712482
TI  - Suppression of the proliferation of Ras-transformed cells by fluoromevalonate, an
      inhibitor of mevalonate metabolism.
AB  - Mevalonate is the precursor of a number of different products potentially
      required for the growth of cells, including the prenylated oncoprotein Ras. To
      determine whether inhibition of mevalonate metabolism would selectively block
      proliferation of Ras-transformed cells, 6-fluoromevalonate (Fmev), an inhibitor
      of diphosphomevalonate decarboxylase, was used to block the synthesis of prenyl
      derived lipids and prenylated proteins in interleukin-3 (IL-3)-dependent FDC-P1
      cells (control FDC-P1 cells) and FDC-P1 cells transformed with oncogenic Ras
      (RasDC cells) that proliferated in the absence of IL-3. Fmev completely inhibited
      synthesis of prenyl-derived lipids and prenylated proteins and blocked
      proliferation of FDC-P1 and RasDC cells. Restoration of the proliferation of Fmev
      blocked FDC-P1 cells required both an exogenous source of cholesterol and
      prevention of the accumulation of mevalonate and the mevalonate phosphates with
      lovastatin. In contrast, ongoing IL-3-independent proliferation of Fmev-blocked
      RasDC cells was not completely restored by providing exogenous cholesterol and
      preventing the accumulation of inhibitory mevalonate product(s). However, these
      cells proliferated when cultures were supplemented with IL-3 together with
      exogenous cholesterol and lovastatin, implying that Fmev had prevented Ras
      dependent, IL-3-independent growth. Fmev markedly diminished total cellular Ras
      in RasDC cells. In contrast, lovastatin depleted membrane-associated Ras and
      increased cytosolic Ras but did not diminish total cellular Ras. These data
      indicate that Fmev depletes total cellular Ras and specifically inhibits the
      autonomous growth of Ras-transformed cells.

PMID- 7712483
TI  - Association between sialyl Lewis(a) expression and tumor progression in melanoma.
AB  - Twenty-three primary and 27 metastatic melanoma lesions and 17 pigmented nevi
      lesions were tested utilizing the immunoperoxidase reaction with anti-sialyl
      Lewis(a) (sLea) and anti-sLex mAbs.sLea was expressed in 9, 25, and 5 and sLex
      was expressed in 6, 11, and 2 of these lesions, respectively. Expression of sLea
      in melanocytic tumors is associated with tumor progression. Serum levels of sLea
      and sLex were analyzed by a sandwich assay using mAbs in 25 melanoma patients.
      Only 2 patients at stage 4 showed higher levels of sLea and sLex than did normal
      control subjects. Moreover, sLea and sLex were expressed in 1 and 2 of 5 human
      melanoma cell lines, respectively, and expression of sLex and sLex was not
      modulated by cytokines. These findings suggest that the expression of sLea in
      melanocytic tumors is correlated with disease progression.

PMID- 7712484
TI  - Detection and cloning of a common region of loss of heterozygosity at chromosome
      1p in breast cancer.
AB  - The short arm of chromosome 1 is frequently affected by rearrangements in a
      variety of human malignancies. Genetic alterations, predominantly deletions,
      which are indicative of the presence of a putative tumor suppressor gene at
      chromosome 1p, are observed in breast cancer. In order to define the altered
      locus, eleven highly polymorphic microsatellite markers on chromosome 1p were
      used to detect loss of heterozygosity. We analyzed 52 cases of breast cancer and
      found 4 common deleted regions at chromosome 1p. Twenty-two of 52 (42%)
      informative patients showed at least 1 affected locus. The region most frequently
      exhibiting loss of heterozygosity was 1p31 (11/39; 28%); the other three common
      deleted regions were 1p36 (10/44; 23%), 1p35-36 (5/40; 13%), and 1p13 (8/39;
      21%). These data suggest that one or more putative tumor suppressor genes may
      reside on chromosome 1p. We have cloned the entire region of interest at 1p31 in
      yeast artificial chromosomes. This yeast artificial chromosome contig can be used
      for fine mapping of the region and cloning of the candidate tumor suppressor
      gene.

PMID- 7712485
TI  - Drug resistance and gene amplification potential regulated by transforming growth
      factor beta 1 gene expression.
AB  - Transforming growth factor beta 1 (TGF-beta 1) regulates a multitude of diverse
      biological functions in mammalian cells, and there is good evidence that aberrant
      expression of this growth factor can play an important role in mechanisms of
      malignant progression. We show that a TGF-beta 1-overexpressing mouse 10T1/2 cell
      line transfected with a TGF-beta 1 sequence that allows the synthesis of
      bioactive growth factor exhibits reduced sensitivity to the cytotoxic effects of
      the drug N-(phosphonacetyl)-L-aspartate (PALA) in colony-forming experiments.
      Furthermore, six independent 10T1/2 TGF-beta 1-transfected cell lines containing
      TGF-beta 1 gene expression under the control of a zinc sulfate-responsive
      metallothionein promoter were selected. In all cases, sensitivity to PALA
      cytotoxic effects was significantly reduced when cells were cultured under
      conditions that led to elevated levels of TGF-beta 1 gene expression when
      compared to cells containing basal levels of this growth factor. Fluctuation
      analysis to determine the rate of PALA resistance was performed with several TGF
      beta 1-transfected cell lines in which growth factor expression was regulated by
      the metallothionein promoter. We observed significantly higher rates of PALA
      resistance/cell/generation in cell populations expressing high levels of TGF-beta
      1 than in the same cells expressing relatively low levels of this growth factor.
      The only mechanism known for PALA resistance in mouse cells involves the
      amplification of the gene coding for the protein target of PALA, CAD, a
      multifunctional polypeptide containing carbamyl phosphate synthetase, aspartate
      transcarbamylase, and dihydroorotase. Southern blot analysis of colonies that
      survived normally cytotoxic concentrations of PALA exhibited CAD gene
      amplification. In total, these observations indicate that aberrant expression of
      TGF-beta 1 gene expression decreases the genetic stability of 10T1/2 cells,
      leading to increased rates of drug resistance and elevated gene amplification
      potential. The results of this study indicate a new malignancy related function
      for TGF-beta 1 alterations and suggest a novel role for aberrant expression of
      this growth factor in mechanisms of drug resistance and tumor progression.

PMID- 7712486
TI  - Defective G2 checkpoint function in cells from individuals with familial cancer
      syndromes.
AB  - The early events in the G2 checkpoint response to ionizing radiation (IR) were
      analyzed in diploid normal human fibroblasts (NHFs) and fibroblasts from patients
      with two heritable cancer syndromes. Exposure to gamma-radiation of
      asynchronously growing NHFs resulted in a rapid reduction in the number of cells
      in mitosis (G2 delay) and was accompanied by a quantitatively similar reduction
      in the p34CDC2/cyclin B in vitro histone H1 kinase activity as compared with sham
      treated controls. This G2 delay was strong by 1 h following exposure to IR,
      maximal by 2 h, and was accompanied by an accumulation of tyrosine-phosphorylated
      p34CDC2 molecules. In contrast, fibroblasts from individuals with ataxia
      telangiectasia displayed significantly less reduction of the mitotic index or
      histone H1 kinase activity after IR. Low passage fibroblasts from individuals
      with Li-Fraumeni syndrome having one wild-type and one mutated p53 allele were
      similar to NHFs in their immediate G2 checkpoint response to IR, as were NHFs
      expressing the human papilloma virus type 16 E6 gene product (functionally
      inactivating p53) and low passage cells from p53-deficient mouse embryos.
      However, the p53-deficient fibroblasts were genomically unstable and became
      defective in their early G2 checkpoint response to IR. Furthermore, immortal Li
      Fraumeni syndrome fibroblasts lacking wild-type p53 displayed an attenuated G2
      checkpoint response. These results link the early events in G2 checkpoint
      response to IR in NHFs with a rapid inhibition of p34CDC2/cyclin B protein kinase
      activity and demonstrate that while not required for this immediate G2 delay,
      lack of p53 can lead to subsequent genetic alterations that result in defective
      G2 checkpoint function.

PMID- 7712487
TI  - The scid factor on human chromosome 8 restores V(D)J recombination in addition to
      double-strand break repair.
AB  - The murine severe combined immune deficiency mutation (scid) is characterized by
      a lack of B- and T-lymphoid cells due to a defect in lymphoid V(D)J
      recombination. Moreover, defective rejoining of DNA double-strand breaks (dsb) in
      scid cells also results in a marked increase in sensitivity to ionizing
      radiation. Recently, the putative human homologue of the murine scid gene locus,
      HYRC1, was assigned to human chromosome 8q11, based on the radiation sensitivity
      of scid cells as compared to scid:human cell hybrids carrying portions of human
      chromosome 8. Given the precedent (e.g., ataxia-telangiectasia) for genes other
      than the affected one being able to complement radiation defects, we were
      interested in determining if the V(D)J recombination defect was also corrected by
      the HYRC1 locus. The V(D)J recombination analysis using extrachromosomal DNA
      substrates in control scid cells (SC3VA2) versus complemented cells (RD13B2)
      indicates that the radiation sensitivity-complemented cells (RD13B2) are also
      fully complemented for the V(D)J recombination reaction, whereas the control
      (uncomplemented) cells (SC3VA2) fail to carry out V(D)J recombination normally.
      Slightly over 60% of the radiation-induced dsb are rejoined even in scid cells,
      and this alternative pathway is temperature sensitive. Only the remaining 30-35%
      of dsb require the introduction of the HYRC1 locus, and this pathway is not
      temperature sensitive. This merely partial contribution of the scid factor to the
      repair process suggests the presence of another pathway of dsb repair. Our
      results indicate that the HYRC1 locus, assigned to human chromosome 8q11, encodes
      the scid factor, which is involved in all V(D)J recombination coding joint
      formation and in 30-35% of dsb repair by the temperature-resistant pathway.

PMID- 7712488
TI  - Effects of tamoxifen administration on the expression of xenobiotic metabolizing
      enzymes in rat liver.
AB  - The nonsteroidal antiestrogen tamoxifen is widely used in breast cancer treatment
      and is currently under evaluation as a chemopreventive agent for individuals at
      high risk of contracting the disease. The effects of tamoxifen administration on
      the expression of xenobiotic metabolizing enzymes in F344 rat liver have been
      investigated. Tamoxifen administration for 7 days produced a dose-dependent
      increase in enzyme expression similar to that reported to be produced by
      phenobarbital. Increases in CYPIIB1, CYPIIB2, CYPIIIA, and microsomal epoxide
      hydrolase mRNA and protein levels in males and females were observed by Western
      and Northern blotting. The expression of CYPIA1, CYPIA2, and gamma-glutamyl
      transpeptidase mRNA was not significantly affected by tamoxifen treatment.
      Tamoxifen was approximately one-tenth as potent an inducer of combined CYPIIB1/2
      mRNA compared with phenobarbital when the two drugs were administered at
      equimolar doses. In addition to the effects observed after short-term tamoxifen
      exposure, increases in CYPIIB1 and CYPIIB2 protein levels were noted after 6 and
      15 months of 250 ppm tamoxifen in the diet. Taken together, these results suggest
      that tamoxifen is a weak phenobarbital-like inducer. However, there are
      significant differences in the induction profiles produced by the two drugs. Most
      significant of these differences was the relatively weak induction of CYPIIB1 but
      striking induction of CYPIIB2 by tamoxifen. In addition, females were often more
      sensitive than males to tamoxifen, especially at low doses. These differences
      suggest that tamoxifen and phenobarbital do not use identical molecular
      mechanisms to produce enzyme induction. It is possible that the effects of
      tamoxifen are a result of phenobarbital-like properties coupled with the effects
      of tamoxifen-induced hormonal perturbations in the animal. In sum, tamoxifen
      induces enzyme expression in rats at a dose comparable, on a mg/kg basis, to the
      dose women receive for disease management, suggesting these results may be
      significant for human exposure.

PMID- 7712489
TI  - Differential expression of pleiotrophin and midkine in advanced neuroblastomas.
AB  - Pleiotrophin (PTN) and midkine (MK) are members of a new family of neurotrophic
      factors whose expression is developmentally regulated. PTN also transforms NIH
      3T3 cells, and MK is mitogenic to certain cell lines. Neuroblastomas are tumors
      derived from neural crest cells, and recent studies have revealed that the
      biology of these tumors is at least partly regulated by neurotrophic factors and
      their receptors. To examine the expression of PTN and MK in neuroblastoma, we
      analyzed their mRNA expression in 72 primary neuroblastomas and 11 neuroblastoma
      cell lines as well as other tissues and cell lines. PTN is highly expressed in
      favorable neuroblastomas (stages I, II, and IV-S, n = 44), whereas it is
      expressed at a significantly lower level in advanced tumors (stages III and IV, n
      = 28, P = 0.003). PTN is not expressed in either aggressive neuroblastomas with N
      myc amplification or in neuroblastoma cell lines. Moreover, the expression
      pattern of PTN was similar to that of TRK-A, the high affinity receptor for nerve
      growth factor, in that it is correlated with a favorable prognosis (P < 0.004).
      In contrast, MK is highly expressed in almost all primary neuroblastomas and cell
      lines and showed no correlation with disease stage or N-myc amplification. These
      results suggest that differential expression of PTN and MK may have an important
      role in regulating growth and differentiation of neuroblastomas.

PMID- 7712491
TI  - 2nd European symposium. The insertion of pediatric neurosurgery into the European
      health care system: professional, social, cost-benefit aspects. June 3-6, 1993,
      Orta San Guilio, Italy. Proceedings.

PMID- 7712490
TI  - Expression of brain-derived neurotrophic factor and p145TrkB affects survival,
      differentiation, and invasiveness of human neuroblastoma cells.
AB  - A large number of poor prognosis neuroblastoma (NB) tumors constitutively express
      brain-derived neurotrophic factor (BDNF) and variably express the gene for its
      tyrosine kinase (Trk) receptor TrkB. Good prognosis NB tumors typically express
      high levels of TrkA mRNA, which encodes the signal transducing receptor for nerve
      growth factor, p140TrkA. These neurotrophins are necessary for neural cell
      survival and differentiation. This study evaluates the effects of activation of
      the BDNF-TrkB signal transduction pathway on the growth, survival, morphology,
      and invasive capacity of NB cells. We find that the addition of BDNF to SY5Y
      cells induced to express p145TrkB by retinoic acid treatment does not
      significantly affect cell proliferation yet will support cell survival.
      Activation of the BDNF-TrkB signal transduction pathway stimulates disaggregation
      of cells and extension of neuritic processes which can be blocked by a BDNF
      neutralizing antibody. Treatment of cells with K252a, an inhibitor of Trk,
      reverses the cellular disaggregation. An evaluation of the effects of BDNF and
      nerve growth factor on the ability of NB cells to penetrate basement membrane
      proteins indicated that BDNF stimulated a 2-fold increase while nerve growth
      factor inhibited RA-SY5Y cell invasion. Thus, activation of the p145TrkB signal
      transduction pathway stimulates NB cell survival, disaggregation, and invasion;
      all characteristics of metastatic cells. Furthermore, these studies indicate that
      activation of different Trk signal transduction pathways in NB cells results in
      distinct differences in tumor cell biology and these may be relevant to the
      clinical course of the patients.

PMID- 7712492
TI  - An overview of pediatric oncology as a model for interdisciplinary care.

PMID- 7712493
TI  - A multidisciplinary care unit for congenital intraspinal lipomas.

PMID- 7712494
TI  - The incorporation of pediatric neurosurgery into the European health care system.

PMID- 7712495
TI  - Functioning multidisciplinary care and referral center for cerebral palsy
      children.

PMID- 7712496
TI  - Epilepsy in the pediatric age and its surgical treatment.

PMID- 7712498
TI  - Interventional neuroradiology in children.

PMID- 7712499
TI  - A department of pediatric neurosurgery in a pediatric hospital.

PMID- 7712497
TI  - Developing areas and their cost-benefit correlations: radiosurgery.

PMID- 7712500
TI  - Paediatric neurosurgery--in a general hospital context?

PMID- 7712501
TI  - Various aspects, activities and realities of nursing care.

PMID- 7712502
TI  - Significant problems regarding neurosurgical procedures being performed by non
      neurosurgeons.

PMID- 7712503
TI  - The establishment of a positive working relationship with other pediatric
      subspecialties.

PMID- 7712505
TI  - Future EANS training programs and certification.

PMID- 7712506
TI  - Pediatric neurosurgery in Europe--is it feasible to have evolution and education
      operate in synchrony?

PMID- 7712507
TI  - The family and the sick child.

PMID- 7712504
TI  - The EANS: pediatric neurosurgery and general neurosurgery.

PMID- 7712508
TI  - The place of pediatric neurosurgery in the U.E.M.S.

PMID- 7712510
TI  - What the press needs in order to keep the public responsibly informed.

PMID- 7712509
TI  - The integration of pediatric neurosurgery into the Danish health care system.

PMID- 7712511
TI  - Social services: the link between the family and the community.

PMID- 7712514
TI  - Evidence that the ability to respond to a calcium stimulus in exocytosis is
      determined by the secretory granule membrane: comparison of exocytosis of
      injected bovine chromaffin granule membranes and endogenous cortical granules in
      Xenopus laevis oocytes.
AB  - 1. To understand better the mechanisms which govern the sensitivity of secretory
      vesicles to a calcium stimulus, we compared the abilities of injected chromaffin
      granule membranes and of endogenous cortical granules to undergo exocytosis in
      Xenopus laevis oocytes and eggs in response to cytosolic Ca2+. Exocytosis of
      chromaffin granule membranes was detected by the appearance of dopamine-beta
      hydroxylase of the chromaffin granule membrane in the oocyte or egg plasma
      membrane. Cortical granule exocytosis was detected by release of cortical granule
      lectin, a soluble constituent of cortical granules, from individual cells. 2.
      Injected chromaffin granule membranes undergo exocytosis equally well in frog
      oocytes and eggs in response to a rise in cytosolic Ca2+ induced by incubation
      with ionomycin. 3. Elevated Ca2+ triggered cortical granule exocytosis in eggs
      but not in oocytes. 4. Injected chromaffin granule membranes do not contribute
      factors to the oocyte that allow calcium-dependent exocytosis of the endogenous
      cortical granules. 5. Protein kinase C activation by phorbol esters stimulates
      cortical granule exocytosis in both Xenopus laevis oocytes and X. laevis eggs
      (Bement, W. M., and Capco, D. G., J. Cell Biol. 108, 885-892, 1989). Activation
      of protein kinase C by phorbol ester also stimulated chromaffin granule membrane
      exocytosis in oocytes, indicating that although cortical granules and chromaffin
      granule membranes differ in calcium responsiveness, PKC activation is an
      effective secretory stimulus for both. 6. These results suggest that structural
      or biochemical characteristics of the chromaffin granule membrane result in its
      ability to respond to a Ca2+ stimulus. In the oocytes, cortical granule
      components necessary for Ca(2+)-dependent exocytosis may be missing,
      nonfunctional, or unable to couple to the Ca2+ stimulus and downstream events.

PMID- 7712515
TI  - Endothelin-3 stimulates inositol 1,4,5-trisphosphate production and Ca2+ influx
      to produce biphasic dopamine release from rat striatal slices.
AB  - 1. Real-time monitoring of dopamine (DA) release from rat striatal slices
      demonstrated that endothelin (ET)-3 (0.1-10 microM) produced a biphasic DA
      release consisting of transient and sustained components. When extracellular Ca2+
      was removed, the sustained but not transient response remarkably decreased. 2. ET
      3 (1-10 microM) stimulated an increase in the intracellular Ca2+ concentration
      ([Ca(2+)]i), which also consisted of two components. The external Ca2+ depletion
      inhibited primarily the sustained component of the Ca2+ response to ET-3. 3. ET-3
      increased inositol 1,4,5-trisphosphate (IP3) concentrations in striatal slices.
      This response peaked at 10 to 20 sec and returned to the basal level 2 min after
      stimulation, an event which was in good accord with a prompt and transient phase
      of both cytosolic Ca2+ activity and DA release evoked by ET-3. 4. Thus, ET-3
      produces a transient and a sustained release of DA from striatal slices by
      stimulating intracellular Ca2+ mobilization via IP3 formation and extracellular
      Ca2+ influx, respectively.

PMID- 7712519
TI  - [The human genome].

PMID- 7712517
TI  - [Local production of eicosanoids in patients with ulcerative colitis].
AB  - BACKGROUND: Eicosanoids act obviously as mediators of inflammation in ulcerative
      colitis. The objective of the submitted paper was to assess relations between
      intraluminal concentrations of prostaglandin E and leukotriene B4 and the
      activity of ulcerative colitis evaluated according to clinical, endoscopic and
      histological criteria. METHODS AND RESULTS: In 56 patients with ulcerative
      colitis the PGE concentration was assessed in the rectal dialysate (3H
      Prostaglandin E Radioimmunoassay Kit Ca-501, Clinical Assay Cambridge USA). In 35
      patients with ulcerative colitis the authors assessed the LTB4 concentration in
      the rectal dialysate (Leukotriene B4 3H Assay RPN 70, Amersham, G. Britain). The
      authors proved a statistically significant correlation between the intraluminal
      PGE concentration and the activity of ulcerative colitis according to clinical
      criteria (p < 0.1), endoscopic criteria (p < 0.05) and histological criteria (p <
      0.01). The intraluminal LTB4 concentration correlated significantly with the
      activity of ulcerative colitis according to clinical criteria (p < 0.05). When
      comparing LTB4 values with the activity of the disease according to endoscopic
      and histological criteria, a tendency of rising LTB4 values with increasing
      activity of the disease is apparent. However, a significant relationship was not
      found; this can be explained by the fact that relatively small groups of patients
      were investigated with a relatively great scatter of LTB4 concentrations.
      CONCLUSIONS: During the period of active ulcerative colitis the intraluminal PGE
      concentration rises and correlates with the clinical, endoscopic and histological
      activity. There is also a rise of the intraluminal LTB4 concentration which
      correlates with the clinical activity of the disease. A high eicosanoid
      concentration is found in cases with a severe course and complications.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7712518
TI  - [The spectrum of diseases associated with antineutrophil cytoplasmic antibodies].
AB  - BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) are considered as a
      diagnostic marker of systemic vasculitis and rapidly progressing
      glomerulonephritis. They are frequently associated with other pathological
      conditions. The author's objective was to analyze a group of patients examined at
      the Department of Clinical Immunology of the First Medical Faculty Charles
      University in the course of one year and evaluation of the diagnostic asset of
      the ANCA examination. METHODS AND RESULTS: ANCA was assessed in serum using the
      method of indirect immunofluorescence. In cases of p-ANCA the ELISA test was used
      to assess antimyeloperoxidase antibodies. Clinical data were evaluated on the
      basis of analysis of a questionnaire sent to doctors of patients where ANCA was
      detected. In 1992 1010 specimens were examined and in 115 ANCA was detected. This
      was the case in a group of 65 patients with the following diagnoses: systemic
      vasculitis 26x, systemic immunopathological diseases 12x, renal diseases 9x,
      inflammatory bowel diseases 7x, inflammatory eye diseases 6x, monoclonal
      paraproteinaemia 2x, other 4x. The patients had renal affections (45%),
      affections of the joints (20%), skin (18%), eyes (14%), lungs (12%), GIT (11%),
      ENT (9%), and nerves (9%). Type c in titres above 1:160 was always associated
      with the diagnosis of Wegener's granulomotosis, in other instances c- or x-types
      titres of 1:20 were involved. Antibodies against myeloperoxidase were detected in
      four instances. CONCLUSIONS: The authors confirmed that c-ANCA in high
      concentrations are specific for the predominantly active form of Wegener's
      granulomatosis. The group of patients with p-ANCA is too small to generalize the
      diagnostic impact. Low ANCA concentrations are found in many other diseases. The
      importance of ANCA can be evaluated only in a clinical context and the importance
      of their presence must not be overestimated.

PMID- 7712520
TI  - [The human genome with special emphasis on chromosome 1].
AB  - The development of knowledge of human genomes to the present stage was influenced
      by three specific genetic methodologies. Chromosomology after the beginning of
      the fifties, genetics of somatic cells, which began in the mid-sixties and
      molecular genetics which started at the end of the seventies (1). All
      methodologies contributed in their time to the mapping of genes and the
      construction of gene maps. The submitted review is devoted in particular to
      chromosome 1. Information pertaining to gene mapping helps to elucidate the
      evolution, organization of controlling mechanisms of the pathogenesis of
      hereditary disease, neoplasias, malformations for prenatal and premorbid
      diagnosis and perspectively for gene therapy.

PMID- 7712521
TI  - [Quality assurance in health care and its economic aspects].
AB  - The author defines the term of quality assurance as a cycle of activities to
      ensure the best possibly attainable standard of provided health care and
      characterizes its attributes. Within the range of a review he analyzes different
      constituents of quality assurance, in particular with regard to effectiveness and
      efficiency of health care. In view of the increasing costs of high standard
      health care efforts of optimization and utilization review of health care are an
      essential parallel process of quality assurance. The decisive factor is
      motivation of doctors and health professionals for both mentioned processes,
      which at present lacks systemic support in this country. The author gives an
      account of experience assembled abroad pertaining to suggestions for improvement
      of the standard and optimization in utilization of health care as well as
      inevitable steps for introducing a programme for quality assurance in health
      institutions. In the conclusion the asset of this process is summarized.

PMID- 7712522
TI  - [From the information on a structural gene to the disease].
AB  - Clinical genetics know more than 4000 hereditary diseases: 7.9% of live born
      children are born with one of them. For more than 80% of them mutations of
      structural genes are responsible: either of one or most frequently of several
      genes. The structural gene is a nucleotide sequence in DNA bearing genetic
      information for a primary structure of the peptide (protein) chain. A mutation of
      the structural gene most frequently implies a pathological alteration or loss of
      biological function of the protein coded by it--which leads to the development of
      symptoms of disease. Impaired DNA and impaired expression of its information may
      be caused also by aberration of the chromosome where it is located. Chains of
      causal relationships between the altered information of the structural gene and
      the clinical picture of the disease can be followed up in both directions. so far
      the most frequently used pathway is from a known syndrome to an unknown gene. As
      an example, we may quote the elucidation of the genetic background of Down's
      syndrome. Symptoms of Down's syndrome--trisomy of a 21 autochromosome or at least
      of strip 22 of its q arm in its translocation form--ensue from the abnormally
      enhanced formation of products of genes located there as a result of an increased
      gene dose; so far five are known.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712516
TI  - Hippocampal glucocorticoid receptor expression in the tree shrew: regulation by
      psychosocial conflict.
AB  - 1. This study was conducted to determine whether chronic psychosocial conflict
      alters the expression of glucocorticoid receptor (GR) mRNA in the hippocampus of
      male tree shrews (Tupaia belangeri). 2. To generate probes for the in situ
      hybridization, the tree shrew GR gene was partly cloned. There was a 90% homology
      between the deduced amino acid sequence of the cloned tree shrew GR and that of
      the corresponding human GR sequence. 35S-Labeled riboprobes which had been
      transcribed from the tree shrew GR clone hybridized to pyramidal neurons in all
      subregions of the tree shrew hippocampal formation and to granule neurons in the
      dentate gyrus. 3. After in situ hybridization, the expression of GR mRNA was
      semiquantitatively determined by counting silver grains over single neurons of
      the hippocampal formation of psychosocially stressed tree shrews and control
      animals. After 12 days of social conflict, the number of silver grains in the CA1
      and CA3 pyramidal neurons of stressed animals was significantly lower than in
      controls. No statistically significant differences in mRNA expression were
      observed in the pyramidal neurons of the subiculum and in the granule neurons of
      the dentate gyrus. 4. The present results suggest that psychosocial stress leads
      to a site-specific down-regulation of hippocampal GR via modification of mRNA
      expression.

PMID- 7712523
TI  - Iodine deficiency in Europe.
AB  - Iodine is a trace element present in the human body in minute amounts (15-20 mg
      in adults, i.e. 0.0285 x 10(-3)% of body weight). The only confirmed function of
      iodine is to constitute an essential substrate for the synthesis of thyroid
      hormones, tetraiodothyronine, thyroxine or T4 and triiodothyronine, T3 (1). In
      thyroxine, iodine is 60% by weight. Thyroid hormones, in turn, play a decisive
      role in the metabolism of all cells of the organism (2) and in the process of
      early growth and development of most organs, especially of the brain (3). Brain
      development in humans occurs from fetal life up to the third postnatal year (4).
      Consequently, a deficit in iodine and/or in thyroid hormones occurring during
      this critical period of life will result not only in the slowing down of the
      metabolic activities of all the cells of the organism but also in irreversible
      alterations in the development of the brain. The clinical consequence will be
      mental retardation (5). When the physiological requirements of iodine are not met
      in a given population, a series of functional and developmental abnormalities
      occur (Table 1), including thyroid function abnormalities and, when iodine
      deficiency is severe, endemic goiter and cretinism, endemic mental retardation,
      decreased fertility rate, increased perinatal death, and infant mortality. These
      complications, which constitute an hindrance to the development of the affected
      population, are grouped under the general heading of Iodine Deficiency Disorders,
      IDD (6). Broad geographic areas exist in which the population is affected by
      IDD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712524
TI  - [Cytokine therapy].
AB  - Cytokines, mediators of intercellular communication, penetrate as a new
      therapeutic group in to haematology, oncology, immunology and other disciplines.
      Recently two main spheres of indication of wider clinical use are in the
      foreground: 1. treatment of leukaemias and advanced solid tumours (interferons,
      interleukin-2, tumour-necrosis factor and others) and 2. treatment of impaired
      haematopoiesis (in clinical practice in particular erythropoietin, granulocyte
      macrophage and granulocyte colonies stimulating factor). Other possibilities are
      offered by cytokines in the treatment of viral diseases (in addition to hepatitis
      B and C, perspectively also AIDS), inborn immunodeficiencies, progressive
      systemic sclerosis and other indications. In particular in oncological diseases,
      contrary to original assumptions, monotherapy with cytokines will not be greatly
      extended and a combination of cytokines with classical treatment will be used.
      The limiting factor in addition to cost is the considerable toxicity of some
      cytokines which calls for alternative routes of administration (local,
      compartmental etc).

PMID- 7712513
TI  - Tetrodotoxin-resistant sodium channels.
AB  - 1. Tetrodotoxin (TTX) has been widely used as a chemical tool for blocking Na+
      channels. However, reports are accumulating that some Na+ channels are resistant
      to TTX in various tissues and in different animal species. Studying the
      sensitivity of Na+ channels to TTX may provide us with an insight into the
      evolution of Na+ channels. 2. Na+ channels present in TTX-carrying animals such
      as pufferfish and some types of shellfish, frogs, salamanders, octopuses, etc.,
      are resistant to TTX. 3. Denervation converts TTX-sensitive Na+ channels to TTX
      resistant ones in skeletal muscle cells, i.e., reverting-back phenomenon. Also,
      undifferentiated skeletal muscle cells contain TTX-resistant Na+ channels.
      Cardiac muscle cells and some types of smooth muscle cells are considerably
      insensitive to TTX. 4. TTX-resistant Na+ channels have been found in cell bodies
      of many peripheral nervous system (PNS) neurons in both immature and mature
      animals. However, TTX-resistant Na+ channels have been reported in only a few
      types of central nervous system (CNS). Axons of PNS and CNS neurons are sensitive
      to TTX. However, some glial cells have TTX-resistant Na+ channels. 5. Properties
      of TTX-sensitive and TTX-resistant Na+ channels are different. Like Ca2+
      channels, TTX-resistant Na+ channels can be blocked by inorganic (Co2+, Mn2+,
      Ni2+, Cd2+, Zn2+, La3+) and organic (D-600) Ca2+ channel blockers. Usually, TTX
      resistant Na+ channels show smaller single-channel conductance, slower kinetics,
      and a more positive current-voltage relation than TTX-sensitive ones. 6.
      Molecular aspects of the TTX-resistant Na+ channel have been described. The
      structure of the channel has been revealed, and changing its amino acid(s) alters
      the sensitivity of the Na+ channel to TTX. 7. TTX-sensitive Na+ channels seem to
      be used preferentially in differentiated cells and in higher animals instead of
      TTX-resistant Na+ channels for rapid and effective processing of information. 8.
      Possible evolution courses for Na+ and Ca2+ channels are discussed with regard to
      ontogenesis and phylogenesis.

PMID- 7712512
TI  - Nicotine-related brain disorders: the neurobiological basis of nicotine
      dependence.
AB  - 1. This paper was written at a moment when the dependence liability of nicotine,
      the psychoactive component from tobacco, was the center of a dispute between the
      tobacco manufacturing companies and the scientific community (Nowak, 1994a-c).
      Without being comprehensive, it tries to summarize evidence compiled from several
      disciplines within neuroscience demonstrating that nicotine produces a true
      psychiatric disease, behaviorally expressed as dependence to the drug (American
      Psychiatric Association, 1994). Nicotine dependence has a biological substratum
      defined as "neuroadaptation to nicotine." 2. The first part of the article
      defines terms such as "abuse," "tolerance," "dependence," and "withdrawal." It
      discusses clinical and experimental facts at the whole-organism level, showing
      that animals and humans will seek and self-administer nicotine because of its
      rewarding properties. 3. The second part discusses the neurobiological basis of
      neuroadaptation to nicotine. It presents information on neuroanatomical circuits
      which may be involved in nicotine-related brain disorders, such as the
      mesocorticolimbic pathway and the basal forebrain-frontal cortex pathway. It also
      discusses work from several laboratories, including our own, that support the
      notion of a molecular basis for neuroadaptative changes induced by nicotine in
      the brain of a chronic smoker. 4. Although still under experimental scrutiny, the
      hallmark of neuroadaptation to nicotine is up-regulation of nicotinic receptors,
      possibly due to nicotine-induced desensitization of their function (Marks et al.,
      1983; Schwartz and Kellar, 1985). A correlation between these plastic changes and
      the behavioral data obtained from animal and human experiments is still needed to
      understand dependence to nicotine fully.

PMID- 7712525
TI  - [Cytokine levels in patients with multiple injuries].
AB  - BACKGROUND: The role of cytokines in trauma still has not been satisfactorily
      elucidated. Multiorgan failure (MOF) development should be also under the
      direction of cytokines, endotoxin, and other mediators. METHODS AND RESULTS:
      Therefore we prospectively studied 88 patients with multiple trauma admitted to
      Traumatological Hospital Brno from June 1, 1992 to May 31, 1993. Extent of the
      trauma was determined by Injury Severity Score (ISS), Revised Trauma Score (RTS),
      and TRISS methodology with probability of survival. In study patients was
      investigated concentrations of interleukin 1, 2, 6, and tumor necrosis factor
      (TNF). Of above mentioned cytokines were elevated only IL-6 levels at admission
      and significant correlation with ISS was found (r = 0.32; p < 0.01). MOF
      developed in 23 patients (12 of them died), but it was not possible to predict
      the MOF development nor surviving according to admission levels of cytokines. A
      significant difference was observed in IL-6 levels of MOF patients one day before
      death (439 +/- 111 ng/l) in comparison with MOF patients, who survived (132 +/-
      88 ng/l, p < 0.001). None of 12 MOF patients with IL-6 concentrations above 400
      ng/l survived. CONCLUSIONS: We conclude that IL-6, less TNF, seems to play an
      important role in organism response to multiple trauma, and later elevation in
      these cytokines levels, especially IL-6 level, in MOF patients mean poor
      prognosis. We had found a significant correlation between initial IL-6 level and
      ISS. Other cytokines did not show changes during the study.

PMID- 7712526
TI  - [Use of creatine phosphate in treatment of cardiocerebral syndrome associated
      with acute myocardial infarct in the aged].
AB  - BACKGROUND: The objective of the investigation was to compare possibilities how
      to influence the general neuropsychic symptomatology described as cardiocerebral
      syndrome during the first three days of an acute myocardial infarction (AIM) in
      old age by means of creatine phosphate (CP). METHODS AND RESULTS: The
      investigation which extended over 8 months comprised 50 subjects admitted to the
      coronary unit (CU) because of AIM symptomatology, age 65-93 years (75.1 +/- 5.6
      years). Twenty-five subjects were given, using a uniform protocol, during the
      first three days at the CU, 18 g CP (Neoton, Schiapparelli) by the i.v. rut. The
      control group of 25 subjects (randomized) with AIM of comparable parameters (age,
      sex, location and course of IM) were not given CP. Evaluation of the dynamics of
      mental deterioration by means of a test of cognitive functions (MMS) during the
      first three days after IM by means of simple regression analysis, comparing the
      two groups, revealed a favourable effect of CP on mental functions as compared
      with the control group (p = 0.05). In the CP treated group there was, as compared
      with the control group, on the 1st and 2nd day a lower incidence of stenocardias
      (statistically not significant; p = NS), ventricular dysrhythmias (p = NS) and
      cardiac failure (p = NS). CONCLUSIONS: Administration of creatine phosphate did
      not produce any undesirable side effects. Objective evidence was provided of the
      favourable effect of CP on mental deterioration in cardiocerebral syndrome in AIM
      in old age.

PMID- 7712527
TI  - [The human genome--chromosome 2].
AB  - The author presents a selective review on the gene contents of the second human
      chromosome, in particular with regard to pathogenesis. Among the best known ones
      the author mentions genes the alleles of which cause anomalies of apolipoprotein
      B, disorders of blood clotting caused by defects of C protein and Waardenburg's
      syndrome associated with disorders of the function of one of the regulating genes
      of the PAX family. Variable and constant gene segments of the immunoglobulin
      chain kappa, incl. pseudogenes, can be considered dominating. A new sphere of
      research interest developed in conjunction with the finding of a gene
      conditioning familial non-polypous carcinoma of the large intestine.

PMID- 7712529
TI  - [Fluorescent in situ hybridization in clinical cytogenetics].
AB  - During the last few years molecular biology methods expanded into human
      cytogenetics. This is in close connection with advanced technologies of DNA
      probes preparation and possibilities of their non-radioactive labelling by means
      of enzymatic incorporation of modified nucleotides as well as their hybridization
      with complementary DNA of chromosomes and interphase nuclei. FISH became a useful
      method in the clinical research. We present the short review of FISH
      methodologies and their applications for studies of translocation, deletions,
      amplifications and other chromosomal rearrangements in genetic and oncologic
      patients. The sensitivity of these methods is approximately 1-10 kb and therefore
      precise localization of genes on chromosomes is possible. Except gene mapping
      FISH can be used for comparative genomic mapping (CGH) and for identification of
      chromosomal changes of tumor cells.

PMID- 7712528
TI  - [Hormonal treatment of non-malignant diseases of the breast].
AB  - The authors summarize possibilities of hormonal treatment of non-malignant
      diseases of the mammary gland. Attention is paid in particular to progestins
      (progesterone, derivatives of hydroxyprogesterone, derivatives of 19 nor
      testosterone), their combination with estrogens (hormonal contraceptives,
      minipills) and hormonal substitution therapy, methods of chemoprevention of
      mammary cancer. In conjunction with the subject the authors mention also the
      possibility to use some other preparations (Danazol, Gonadotropin releasing
      hormones, tamoxifen etc.). The authors submit their own pattern of hormonal
      treatment of non-malignant diseases of the mammary gland.

PMID- 7712530
TI  - [A nutritionally defined liquid diet for hemodialyzed patients].
AB  - BACKGROUND: For patients having regular haemodialysis there are no suitable
      complete preparations for general use in case intensive treatment is needed.
      Nutrilac renal is a new preparation of a nutritionally defined liquid diet
      corresponding as to its composition to the needs of haemodialyzed patients. The
      purpose of the present work was to assess whether this preparation when
      administered as a supplement will have a favourable effect on the nutritional
      parameters of haemodialyzed patients. METHODS AND RESULTS: Nutrilac renal was
      administered to haemodialyzed patients for a period of three weeks as a
      supplement meeting 20% of the energy requirements. The protein intake rose from
      0.87 to 0.95 g/kg body weight (p < 0.05), the energy intake from 109 to 126 kJ/kg
      body weight (p < 0.05). As to nutritional parameters, the serum albumin values
      improved (from 25.0 to 29.4 g/l, p < 0.05) and Whitehead's quotient from 1.8 to
      1.5, p < 0.05). The favourable effect on the amino acid spectrum was manifested
      by a significant rise of essential amino acids and those with branched side
      chains (p < 0.01). The preparation did not lead to a rise of potassium, ura and
      vitamin A levels. CONCLUSIONS: The newly developed preparation Nutrilac renal
      exerts a favourable effect on nutritional parameters. Changes in the aminogram
      characterized by an increase of essential amino acids, in particular threonine,
      valine, leucine and isoleucine indicate the high biological value of the protein
      component of the preparation for patients with chronic renal failure.

PMID- 7712532
TI  - [The human genome--chromosome 3].
AB  - The hitherto little investigated third human chromosome contains genes, the
      pathogenic alleles of which are responsible for some diseases, in particular
      retinitis pigmentosa (locus RHO), von Hippel-Lindau syndrome (VHL), epidermolysis
      bullosa (COL7A1) which is also an example of the situation when different alleles
      and thus genotypes of the same gene lead to phenotypes which differ so much that
      they are classified as different diseases. Locuses of the 3rd chromosome
      participate also in cancerogenesis by the development of the oncogenic genotype
      as a result of loss of activity or as activated oncogenes. On the third
      chromosome there is also the locus for alkaptonuria (AKU), a rare metabolic error
      which is relatively widespread in the north-western part of Slovakia.

PMID- 7712531
TI  - [Administration of multivitamin combinations and trace elements in diabetes].
AB  - BACKGROUND: Many free radicals are formed in diabetes mellitus due to the
      oxidative stress in hyperglykemia. The objective of the investigation was to
      evaluate the influence of an antioxidant mixture and trace elements on some
      biochemical parameters in controls and diabetic patients. METHODS AND RESULTS: 13
      controls (6 men and 7 women, the average age was 53 years) and 9 diabetic
      patients (4 men and 5 women, the average age was 52 years) were supplemented with
      multivitamin mixture and trace elements with respect to antioxidant activities.
      Both groups received the same amount of the mixture, controls 50 days, diabetic
      patients 35 days. Blood samples were measured before and after the treatment.
      Renal, liver tests and acid-base balance were not influenced. Apolipoprotein A
      increased significantly (p < 0.05). Glycosylated hemoglobin in the diabetic group
      decreased significantly from 9.4 +/- 1.6 to 7.2 +/- 1.5 mumol fructose/g of
      hemoglobin (p < 0.01). In the diabetic group increased the levels of ionorganic
      phosphorus from 0.99 +/- 0.08 to 1.15 +/- 0.13 mmol/L (p < 0.01), zinc from 10.4
      +/- 1.3 to 14.3 +/- 1.7 mumol/L (p < 0.01), copper from 20.3 +/- 2.3 to 25.9 +/-
      6.3 mumol/L (p < 0.05) and selenium in blood from 0.96 +/- 0.21 to 1.65 +/- 0.38
      mumol/L (p < 0.001). Selenium in blood of the control group increased from 0.88
      +/- 0.26 to 1.66 +/- 0.34 mumol/L (p < 0.001). The activity of superoxide
      dismutase (SOD) in diabetic group increased from 598 +/- 105 to 696 +/- 103 U/g
      of hemoglobin (p < 0.01), the activity of glutathion peroxidase (GSHPx) did not
      change, malondialdehyde (MDA) decreased from 7.1 +/- 1.1 to 5.8 +/- 1.1 mumol/L
      (p < 0.01) and uric acid decreased from 261 +/- 83 to 236 +/- 96 mumol/L (p <
      0.01). CONCLUSIONS: Multivitamin mixture with trace elements significantly
      protects diabetic patients and the control group against injurous actions of free
      radicals. That is confirmed by the decrease of plasmatic malondialdehyde and uric
      acid and by the increase of superoxide dismutase in erythrocytes. The decrease of
      glycosylated hemoglobin reduces the probability of diabetic complications, the
      increase of plasmatic Zn and Se in the diabetic group increased the plasmatic
      antioxidant ability.

PMID- 7712533
TI  - [History of clinical cytodiagnosis. I].

PMID- 7712534
TI  - [Serum insulin levels affect body constitution, blood pressure, serum lipids and
      cardiac dimensions. Observations in clinically healthy offspring from
      hypertensive families].
AB  - BACKGROUND: According to some work hypertension is in a pathogenetic relationship
      with hyperinsulinaemia or is considered to be the consequence of insulin
      resistance. It is, however, also known that there exists a familial
      predisposition for hypertension; according to genetic investigations half the
      family relatives can suffer from hypertension. In conjunction with these views on
      the pathogenesis of hypertension and its familial character the authors outlined
      the following objectives of their investigation: to test clinically and
      metabolically the condition of the offspring of probands with essential
      hypertension requiring systematic treatment. The authors investigated in
      particular indicators of body composition, insulin concentration and its
      relationship to serum levels and some indicators of lean body mass. METHODS AND
      RESULTS. There were 48 offspring (25 men and 23 women) from families of 30
      probands suffering from hypertension. The mean age of the offspring was 38.4 +/-
      7.8 years. They were compared with a group of 72 controls, mean age 35.8 +/- 8.2
      years (36 men and 36 women) without a family history of hypertension and diabetes
      (t-test). The basal insulin concentration (IRI O' = 20.5 +/- 12.8 microU/ml, and
      14.3 +/- 7.3 microU/ml resp., p < 0.01) and basal C peptide (O' = 0.59 +/- 0.31
      pmol/ml and 0.50 +/- 0.20 pmol/ml resp., p < 0.05) were elevated. The offspring
      of probands with hypertension had a higher body weight (BMI = 25.3 +/- 3.5 kg/m2
      and 23.3 +/- 2.5 kg/m2 resp., p < 0.001) a higher ratio of waist hip
      circumferences (0.94 +/- 0.1 and 0.87 +/- 0.1 resp., p < 0.001) similarly as
      blood pressure (131.5 mmHg +/- 11.8 mmHg and 116 mmHg +/- 13.3 mmHg resp., p <
      0.001) and blood sugar level (5.29 +/- 0.61 mmol/l and 4.93 +/- 0.39 mmol/resp.,
      p < 0.01). The authors also found differences in the serum cholesterol levels
      (5.9 +/- 1.3 mmol/l and 5.1 +/- 0.6 mmol/l resp., p < 0.01), HDL cholesterol
      (1.45 +/- 0.50 mmol/l and 1.65 +/- 0.60 mmol/l resp., p < 0.01) and
      triacylglycerol trends (1.66 +/- 1.54 mmol/l and 1.37 +/- 0.96 mmol/l resp., p <
      0.1). On echocardiographic examination the cardiac dimensions were not enlarged,
      however, significant relations (linear regression) were proved in offspring in
      particular as regards the dimensions of the left ventricle and insulin (IRI O
      left atrium p < 0.05, IRI 30-left atrium, p < 0.01. C peptide O-left atrium, p <
      0.05). Between the body mass index, cholesterol, uric acid HDL-cholesterol the
      waist/hip ratio on the one side, the dimensions of the left atrium, thickness of
      septum and posterior wall (p < 0.01-0.001), between insulin and C peptide (p <
      0.001) on the other side even closer relations were found. CONCLUSIONS: Elevated
      insulin concentrations may participate in the development of body composition,
      they influence the lipid transport and blood pressure in clinically healthy
      offspring of probands suffering from hypertension. The relationship between the
      insulin concentration and disposition towards enlargement of the left heart needs
      more detailed investigation.

PMID- 7712536
TI  - [Gynecologic oncology--present trends].
AB  - The incidence of all malignant tumours of the female reproductive organs in our
      country is on average by 40% higher than the worldwide incidence and with the
      exception of carcinoma of the uterine cervix it is still slowly rising.
      Gynaecological oncology emphasizes: prevention with accurate classification of
      premalignant changes to ensure adequate treatment; radical surgery primarily in
      invasive forms as well as with regard to staging as a prerequisite for indication
      of adjuvant treatment; interdisciplinary team cooperation which indicates without
      time losses all therapeutic steps, incl. inoperable tumours, and ensures
      permanent follow-up.

PMID- 7712535
TI  - Molecular genetics of inherited diseases involving human chromosome 4.
AB  - Two molecular genetic strategies have widely been employed to characterize
      candidate genes for human inherited diseases; identification of disease genes via
      positional cloning and characterization of altered candidate genes in affected
      persons. Both approaches allowed to uncover disease genes. A well-known example
      for positional cloning is the identification of the Huntington's disease (HD)
      gene on human chromosome 4. In other diseases such as piebaldism, Hurler/Scheie
      syndrome and a form of autosomal recessive retinitis pigmentosa, the disease gene
      has first been analyzed and later been localized to human chromosome 4. Steady
      progress in the human genome project permits to combine affected families
      pointing to the chromosomal localization of the disease causing defects. Then the
      genes are investigated that are already mapped to this particular region.
      Accordingly the achondrodysplasia gene has been identified within six months
      after its chromosomal localization. In order to evaluate cloned genes as
      potential candidates for disorders linked to chromosome 4, it is important to
      assign all genes to chromosomal (sub)regions. Furthermore in excess of 140
      closely spaced microsatellites on chromosome 4 as well as many "expressed
      sequence tags" will help to narrow in on additional disease genes.

PMID- 7712537
TI  - Introduction of high molecular weight (IgG) proteins into receptor coupled,
      permeabilized smooth muscle.
AB  - The permeability to high molecular weight (IgG, 150 kD) proteins of the plasma
      membrane of receptor-coupled smooth muscles permeabilized with beta-escin was
      determined using confocal microscopy of immunofluorescent tracers and measurement
      of lactate dehydrogenase (LDH, 135-140 kD) leakage. Permeabilized strips of
      rabbit portal vein and guinea pig ileum were incubated in a relaxing solution
      containing mouse anti-smooth muscle alpha-actin antibody and immunostained with
      F(ab')2 labeled with tetramethyl rhodamine isothiocyanate. Confocal light
      microscopy of Triton X-100 and beta-escin permeabilized cells showed homogeneous
      staining of the cytoplasm, whereas in alpha-toxin treated and intact preparations
      only damaged cells at the edges of the strips were stained. Both the Ca(2+)
      sensitizing effect of phenylephrine, in rabbit portal vein, and Ca2+ release by
      carbachol in guinea pig ileum, were retained after permeabilization and the
      treatment with the primary antibody. During the 30 min permeabilization, 38%, and
      within the next 75 min an additional approximately 30%, of the total LDH leaked
      out from the beta-escin-treated group, but not from the alpha-toxin-treated group
      (3.2%). The responsiveness to agonist and maximum contractility was improved if
      the preparations were incubated during the introduction of proteins at 4 degrees
      C, rather than 24 degrees C. Ca(2+)-independent myosin light chain kinase (61 kD)
      contracted the permeabilized portal vein in the absence of free Ca2+ (pCa < 8).
      In conclusion, permeabilization with beta-escin allows the transmembrane passage
      of 150 kD proteins under our experimental conditions that also retain receptor
      coupled signal transduction.

PMID- 7712538
TI  - Protein kinase C regulates calmodulin expression in NRK cells activated to
      proliferate from quiescence.
AB  - We have investigated the levels of calmodulin protein and calmodulin mRNA species
      during proliferative activation of NRK cells. Cells activated to proliferate from
      quiescence started to replicate DNA at 15 h, reaching a maximum at 20 h after
      serum addition. The maximum of mitosis was observed at 24 h. Quiescent cells
      showed a calmodulin concentration of 1.5 ng/micrograms of protein. At 10 h after
      serum addition the amount of calmodulin started to increase, reaching values of
      3.0 ng/micrograms of protein at 24 h. NRK cells expressed predominantly 3 species
      of calmodulin transcripts: the 1.7 kb from CaM I, the 1.4 kb from CaM II and the
      2.3 kb from CaM III. The amount of all the 3 transcripts was low in quiescent
      cells and 10 h after activation the levels were already high, reaching a maximum
      around 20 h. At the latter time the amount of the 3 calmodulin mRNAs was 5-10
      fold higher than in serum starved cells. Run-on experiments showed that at 20 h
      after activation the transcription rates of the 3 calmodulin genes were higher
      than in quiescent cells. The addition of protein kinase C inhibitors to the
      cultures blocked the increase of the calmodulin transcripts while inhibitors of
      protein kinase A did not have any effect. Moreover, the addition of submitogenic
      doses of phorbol 12-tetradecanoate induced the increase of all 3 calmodulin
      transcripts. These results indicate that protein kinase C regulates calmodulin
      expression when NRK cells are activated to proliferate.

PMID- 7712539
TI  - Delayed activation of plasma membrane Ca2+ pump in human neutrophils.
AB  - The interplay between Ca2+ efflux mechanisms of the plasma membrane (PM) and
      transient changes of the cytosolic concentration of ionized calcium ([Ca2+]i) was
      studied in suspensions of human neutrophils loaded with the [Ca2+]i indicator,
      Fura-2. To reveal Ca2+ efflux through PM the interference of intracellular Ca
      stores was prevented by preincubating the cells in the presence of EGTA,
      thapsigargin, and ionomycin. Addition of econazole prevented varying entry of
      divalent cations regulated by the filling state of Ca stores. The preincubation
      seemed to empty and permeabilize virtually all Ca stores, ensuring that the
      monitored changes of [Ca2+]i were caused exclusively by PM Ca2+ transporters.
      Following preincubation, the addition of CaCl2 induced, mediated by ionomycin, a
      transient rise of [Ca2+]i, a spike, eventually decreasing to an intermediary
      [Ca2+]i level. The ATP-dependent decrease of [Ca2+]i terminating the spike was
      abolished by the calmodulin antagonist, N-(6-aminohexyl)-1-naphthalenesulfonamide
      (W-7), but not by the protein kinase C inhibitor, staurosporine, nor by Na(+)
      free medium, suggesting that neither activity of protein kinase C nor Na+/Ca2+
      exchange was necessary for generation of the Ca2+ spike. In conclusion, the PM
      Ca2+ pump was responsible for the Ca2+ spike by responding to the rapid rise of
      [Ca2+]i by a delayed activation, possibly involving calmodulin. This
      characteristic feature of the PM pump may be important for the generation of
      cellular [Ca2+]i spikes in general.

PMID- 7712540
TI  - Intracellular calcium signaling induced by thapsigargin in excitable and
      inexcitable cells.
AB  - Signaling between intracellular Ca2+ stores and cell membrane channels or
      transporters is important to Ca(2+)-based second messenger systems. Two
      hypotheses, the capacitative and the Ca(2+)-induced Ca(2+)-influx models have
      been proposed to explain aspects of this signaling. In this study, we examined
      the applicability of these models in neuroendocrine (PC12), neuronal (dorsal root
      ganglion), immune (spleen), and fibroblast (3T3) cells. We used thapsigargin
      (TPG) to deplete specific intracellular Ca2+ stores and to increase the
      cytoplasmic Ca2+ concentration ([Ca2+]), and Ca2+ free medium to prevent Ca2+
      influx and lower cytoplasmic [Ca2+]. We demonstrate that, although TPG causes an
      increase of [Ca2+]i in all cells examined, the subsequent stimulation of Ca2+
      influx varies from high in spleen, to moderate in 3T3 and PC12, to undetectable
      in DRG cells. All cell types exhibited Ca2+ influx when Ca2+ was added to the
      medium following an exposure to Ca(2+)-free medium. Without added provisions, the
      two aforementioned hypotheses are inadequate in explaining the TPG-induced Ca(2+)
      influx in all cell types. These results support the hypothesis of the existence
      of unique Ca2+ channels or transporters in spleen cells that operate subsequent
      to TPG treatment and are distinct from the voltage-gated Ca2+ channels and Ca(2+)
      activated non-selective cation channels present in excitable cells.

PMID- 7712541
TI  - Rise in cytoplasmic Ca2+ induced by monensin in bovine medullary chromaffin
      cells.
AB  - Monensin, a Na+/H+ exchanger, induces catecholamine secretion from adrenal
      chromaffin cells by an unknown mechanism. We found and report here that in bovine
      chromaffin cells, monensin evokes profound changes in [Ca2+]i which were measured
      by means of the fluorescent Ca2+ indicator Indo-1. Application of monensin (10
      microM) generated a marked [Ca2+]i rise. Removal of external Ca2+ did not prevent
      the elevation of [Ca2+]i, though it was significantly decreased. In the presence
      of nifedipine (10 microM) or tetrodotoxin (3 microM) the monensin-induced [Ca2+]i
      rise remained unchanged. In contrast, in the absence of extracellular Na+ the
      [Ca2+]i rise was abolished. Addition of caffeine (40 mM) at the peak response
      generated by monensin produced a further increase in [Ca2+]i, which was
      independent of external [Ca2+] or [Na+]. After depletion of the IP3-sensitive
      compartment by thapsigargin (1 microM), caffeine still induced a rise in [Ca2+]i
      while the monensin response was absent. We concluded that the origin of the Ca2+
      for the [Ca2+]i increase elicited by the Na+/H+ exchanger in chromaffin cells is
      not the extracellular space. Clearly there seems to be at least two intracellular
      Ca2+ stores, one of which is affected by monensin. This Ca2+ pool, which is
      different than the pool stimulated by caffeine, is sensitive to the extracellular
      [Ca2+] and to thapsigargin. Our data are compatible with the idea that the
      monensin mediated Na+ entry could activate the production of inositol
      trisphosphate and this in turn could trigger Ca2+ release from the endoplasmic
      reticulum.

PMID- 7712542
TI  - Rapid synchrony of nuclear and cytosolic Ca2+ signals activated by muscarinic
      stimulation in the human tumour line TE671/RD.
AB  - The functional properties of muscarinic cholinergic receptors have been studied
      in single cells of the TE671/RD human line. Muscarinic stimulation causes large
      and quick elevations of cytosolic Ca2+ in the majority of the cells; these
      persist even in the absence of external Ca2+. Electrophysiological experiments
      reveal, in addition to the expected nicotinic current, the activation of a K(+)
      specific current in response to muscarine. The cell nucleus appears freely
      permeable to the acid form of Fura-2 and the cytosolic Ca2+ changes easily spread
      into the nucleus, suggesting free diffusion through nuclear pores. Under
      appropriate Fura-2 loading conditions, fast (up to 0.5 Hz) Ca2+ oscillations can
      be observed, usually originating from a restricted cytosolic region. This
      phenomenon is reflected in fast oscillations of the Ca(2+)-activated K+ current.

PMID- 7712543
TI  - Intracellular calcium handling in isolated ventricular myocytes from
      cardiomyopathic hamsters (strain BIO 14.6) with congestive heart failure.
AB  - Intracellular [Ca2+]i handling has been shown to be altered in isolated
      ventricular myocytes from patients with terminal heart failure. The aim of this
      study was to evaluate if alterations of intracellular [Ca2+]i handling and
      triggering Ca2+ currents in cardiomyopathic hamsters (strain BIO 14.6) with
      congestive heart failure might be similar to changes found in myocytes of
      patients with terminal heart failure and, therefore if the hamster might serve as
      a model for heart failure in man. Cells were isolated from hearts of hamsters
      developing hereditary cardiomyopathy (CMP) (strain BIO 14.6) at 12-14 months of
      age with overt signs of congestive heart failure. Results were compared with age
      matched, undiseased control animals (CTRL). [Ca2+]i transients and Ca2+ currents
      were recorded simultaneously from isolated cells under voltage clamp perfused
      internally with the Ca2+ indicator, Fura-2. Ca2+ current densities in myocytes
      from CMP hamsters were -6.6 +/- 0.6 versus -8.3 +/- 0.5 microA/cm2 (P < 0.05) in
      CTRL. Resting [Ca2+]i levels were not significantly different. Peak [Ca2+]i
      transients were significantly decreased in CMP cells (450 +/- 52 nM versus 1031
      +/- 98 nM in CTRL, P < 0.05). The rate of diastolic [Ca2+]i decay was slower in
      cells from CMP animals (t1/2: 167 +/- 19 versus 109 +/- 16 ms; P < 0.05). A
      moderate negative correlation was found between cell surface area and [Ca2+]i
      transients (r = 0.42; P < 0.05). It is concluded that changes of intracellular
      [Ca2+]i handling may play an important role in altered contractility of the
      myocardium of hamsters with hereditary cardiomyopathy in the late stage of
      congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712545
TI  - Establishing percentiles for junior tennis players based on physical fitness
      testing results.
AB  - An important aspect of this study was the establishment of a data base. A broad
      data base allows for data on certain parameters to be greatly expanded and will
      also enhance the use and interpretation of statistical methods. A longitudinal
      study of these variables may also assist in monitoring the players' progress over
      a period of time, and can provide a useful supplement to subjective coaching
      appraisals. The means and standard deviation for each test were calculated
      according to the USTA age and gender groups, that is, 12s, 14s, and 16s for each
      separate gender. Additionally, the mean and standard deviations for the ages,
      heights, and weights of each grouping were also calculated. Once the means and
      standard deviations were calculated, percentile tables were developed for each of
      the USTA groupings (by age and gender). The percentiles for each USTA test are
      presented in Appendix 1. A percentile is defined as the point on the distribution
      below which a given percentage of the scores is found. Percentiles can provide a
      norm-referenced interpretation of an individual score within a distribution that
      often consists of scores from a comparable group of individuals. Using the USTA
      protocol, players and coaches now have a set of normative data by which
      individual player's fitness scores may be compared with participants of the USTA
      Area Training Centers (See appendix 1). From the test results, coaches and
      players can determine which fitness areas need to be improved for athletes on an
      individual basis. Specific training programs can then be designed based on an
      athlete's fitness testing results. Proper interpretation of the USTA fitness
      testing data base results can lead to an easy way to determine the relative
      position of a given fitness score in the distribution, recognizing weaker areas
      for the purpose of injury prevention and performance enhancement. Each player can
      be given a profile detailing their percentile rank relative to other area
      training center participants in their age group. Results of these fitness scores
      can prove to be of great assistance to coaches in designing proper training
      programs and may also give physicians some indication which weaknesses may
      potentially lead to injury. The sample player shown in Figure 1 and Table 2 is a
      right-handed female player ranked in the 12-years-old-and-under division. Her
      results clearly indicate very high scores in the agility and speed categories;
      however, her scores in the strength and power areas were significantly lower than
      other area training center participants in her age group.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7712544
TI  - Characterisation of an intracellular Ca2+ pump in Dictyostelium.
AB  - Calcium uptake by microsomal membranes from the cellular slime mould
      Dictyostelium discoideum was measured using Calcium Green-2 as a fluorescent
      probe of external free Ca2+ concentration. High-affinity Ca2+ uptake was found to
      be completely inhibited by low concentrations of vanadate, but not by
      thapsigargin, suggesting that the activity is mediated by a Ca(2+)-ATPase
      distinct from sarco(endo)plasmic reticulum type of higher animal cells. On
      sucrose density gradients, Ca2+ uptake distributes with vacuolar proton pump
      activity and part of the observed Ca2+ uptake is dependent on the pH gradient
      generated by the vacuolar-type H(+)-ATPase, indicating that the Ca2+ pump is
      located on both acidic and non-acidic vesicles, possibly derived from the H(+)
      ATPase-rich contractile vacuole complex.

PMID- 7712546
TI  - Rehabilitation of the shoulder in tennis players.
AB  - The tennis player places unique demands on the shoulder by creating a high risk
      for overuse and overloading of the soft tissues. Tennis requires concentric work
      to position and move the arm, eccentric work to stabilize the shoulder, effective
      depression of the humeral head to avoid impingement in the overhead position, and
      normal stability to prevent secondary impingement. The tennis serve produces
      enormous angular velocities about the shoulder joint. A comprehensive
      rehabilitation program has been described in which the therapist, trainer,
      player, and physician alike need to have an understanding of the basic
      biomechanics of this sport. This program can be used to treat the painful
      shoulder, prevent injury, and enhance performance.

PMID- 7712547
TI  - Surgical treatment of shoulder injuries in tennis players.
AB  - There are a number of disorders that affect the shoulder of the tennis player.
      The majority of these disorders are approached conservatively at first, and
      surgery is generally reserved for those with advanced stages of disease, or those
      who fail conservative treatment. Most surgical procedures for the shoulder are
      done open; however, arthroscopic techniques are advancing rapidly, and are
      expected to eventually supersede open surgical procedures. In either case, the
      postoperative rehabilitation program is an essential part of the surgical
      treatment of these disorders, and should not be neglected.

PMID- 7712548
TI  - Knee pain in tennis players.
AB  - Knee injuries are relatively common in tennis, comprising about one fifth of all
      tennis injuries. The most common injuries are meniscus injuries and degenerative
      cartilage problems in middle aged and elderly recreational players. In younger
      individuals, patellofemoral pain syndromes are the most frequent and intriguing
      problems. Knee overuse syndromes occur more commonly on surfaces such as all
      weather concrete because they are more fatiguing and have higher friction than
      clay surfaces do.

PMID- 7712549
TI  - Patellofemoral dysfunction in tennis players. A dynamic problem.
AB  - Our mechanically-based dynamic approach to PFD focuses on immediate alteration of
      symptoms during functional activities. This approach and this article focuses on
      mechanically-based PFD. The athlete benefits from this approach because if
      symptom alteration is successful, activity modification may not be necessary. The
      success of our ability to alter symptoms is an excellent indicator of the
      athlete's rehabilitation prognosis. Although remaining active is an immediate
      benefit to the athlete, this program focuses on correction of mechanical faults
      and musculoskeletal imbalances in an attempt to permanently eliminate symptoms.
      As noted, diagnosis of PFD is relatively easy to determine, whereas treatment
      often is both controversial and frustrating. To date, the authors have had great
      success treating tennis players and other athletes with this approach. We believe
      that our success rate is an indicator of the value of this program. A
      standardized yet adaptable approach to treatment and follow-up is recommended to
      understand the natural course and long term prognosis of these athletes. As we
      continue to investigate this problem it is clear that there are many unanswered
      questions about PFD. Many of these questions could be more easily answered if an
      objective way to classify PFD can be developed, as well as a way to evaluate,
      treat, and follow-up PFD on a long-term basis. The authors are confident,
      however, that this functional approach provides a simple and dynamic way to
      rehabilitate athletes with PFD.

PMID- 7712550
TI  - Rehabilitation of the lower extremity.
AB  - Rehabilitation of the lower extremities has fallen into two basic categories
      known as open and closed kinetic chain activities. Closed kinetic chain exercises
      are functional exercises specific to sport movement patterns. Exercises performed
      with a variety of equipment may be classified as closed kinetic chain. Program
      development should include a variety of functional exercises using variable
      volumes and intensities of resistance for maximum results.

PMID- 7712554
TI  - The older athlete with tennis elbow. Rehabilitation considerations.
AB  - Athletic injury in the older adult community is likely to have more serious
      repercussions than a similar injury in a young adult because of age-related
      change. A balance between adequate rest and restoration of movement and strength
      must be established. Recovery from an athletic injury should be expected, but
      older tissues take more time to heal. Rest, cold application, avoidance of
      stressful movements, and compression are known to be highly effective for
      alleviating symptoms, but other modalities may further enhance recovery. To avoid
      reinjury and further complications, strength and ROM must be fully restored in
      the older adult athlete. A careful evaluation of causative factors, treatment
      efficacy, and the recovery phase is imperative.

PMID- 7712553
TI  - Low back injury.
AB  - Low back injuries occur commonly in tennis, but the pathophysiologic,
      biomechanical, and clinical characteristics are not well defined. Tennis players
      may be at an increased risk of lumbar disc pathology from rotational and
      hyperextension shearing effects. Treatment of low back injury at present is
      empiric, but sport-specific lumbar stabilization and unloading of the lumbar disc
      should be developed. Prospective longitudinal research protocols are needed to
      study the lumbar spine in tennis players.

PMID- 7712552
TI  - Fluid and electrolyte losses during tennis in the heat.
AB  - A tennis player's metabolism during play in a hot environment generates an
      abundance of heat, which is primarily eliminated from the body by evaporation of
      sweat. An individual's on-court rate of fluid loss will depend on the
      environmental conditions, intensity of play, acclimatization, aerobic fitness,
      hydration status, age, and gender. Unless fluid intake closely matches sweat
      loss, a progressive and significant body water deficit may develop that will
      proportionately impair cardiovascular and thermoregulatory functions. As a
      result, a player can experience an increase in core temperature, premature
      fatigue, performance decrements, and an increased potential for heat illness.
      Although sweat is hypotonic compared to plasma, extended tennis play, in a hot
      environment, can lead to sizable Na+ and Cl- losses. Also, ad libitum drinking
      often leads to involuntary dehydration in these conditions. Therefore, for tennis
      play and training in the heat, it is important to follow a hydration plan that
      will minimize on-court water deficits, by optimizing fluid availability,
      consumption, and absorption. For tennis matches greater than 1 hour in duration,
      a CHO-electrolyte drink (as described earlier) is the recommended on-court
      beverage.

PMID- 7712551
TI  - Lower leg and foot injuries in tennis and other racquet sports.
AB  - Injuries to the lower extremity are common in racquet sports. These can be either
      acute or chronic. Although acute injuries usually respond to treatment, chronic
      injuries are often less amenable to treatment. The occurrence of both kinds of
      injuries, however, can often be prevented by proper training techniques including
      stretching and strengthening exercises. These exercises are also important
      components of a proper rehabilitation program.

PMID- 7712555
TI  - Racquet sports. The future.
AB  - The future of sports medicine and the affiliated sciences is extremely promising
      within the world of tennis. Players and coaches have recognized the important
      role of science in supporting tennis training and development. The USTA has
      established the sport sciences as a basis for all programs and policies. The
      challenges for the future appear clear: 1. To promote tennis specific research
      that specifically addresses the training, development, and competitive needs of
      coaches and athletes. 2. To access sport science information generated in other
      countries or by other sports that maybe useful to tennis in the United States. 3.
      To disseminate sport science information in user-friendly language to the widest
      possible audience. 4. To support all classifications of tennis players with sport
      science information relevant to their group including all ages and skill levels.
      Much has been accomplished in the past 10 years to support athlete development,
      but the promise of the future is exciting and will require teamwork within the
      tennis and scientific communities by people who love tennis.

PMID- 7712557
TI  - The biomechanics of tennis elbow. An integrated approach.
AB  - Tennis elbow afflicts 40% to 50% of the average, recreational tennis players;
      most of these players more than 30 years of age. Tennis elbow is thought to be
      the result of microtrauma, the overuse and inflammation at the origin of the ECRB
      as a result of repeated large impact forces created when the ball hits the racket
      in the backhand stroke. Several authors have found that EMG activity in the ECRB,
      the muscle and tendon complex afflicted in tennis elbow, is high during the
      acceleration and early follow-through phases of the groundstrokes and during the
      cocking phase of the serve. Unfortunately, none of the authors gave evidence to
      support the claim that muscle activity in the ECRB at ball contact is high. In
      the one-handed backhand, the torques at impact (17-24 nm) will be absorbed by the
      tendons of the elbow. Giangarra and his colleagues observed that the two-handed
      backhand "allows the forces at ball impact to be transmitted through the elbow
      rather than absorbed by the tissues at the elbow." Other authors have reported
      that players using a two-handed backhand will rarely develop lateral
      epicondylitis, because the helping arm appears to absorb more energy and changes
      the mechanics of the swing. As seen by Morris and colleagues, Giangarra and
      associates, and Leach and colleagues, players who utilize the two-handed backhand
      have a very low incidence of tennis elbow. These three studies conclude that the
      two-handed backhand stroke is probably the most effective backhand stroke to
      prevent lateral tennis elbow. Studies show that wrist extensors are highly
      involved in all strokes (serve, forehand, and both one- and two-handed backhand
      strokes). This relatively high involvement (40%-70% MVC) throughout play may
      result in overload of this muscular group. Thus, tennis elbow may be caused
      simply by continued use of this muscular system in all strokes, and not just
      because of the high forces absorbed at impact. Another theory concerning impact
      states that if the extensor group is already at near maximum contraction,
      vibrations and twisting movements are transferred directly through the muscle
      (muscle stiffness at this point would be great) to the tendinous insertion,
      causing repeated microtrauma. If the muscle is the stiffest element in the
      system, the force will be transferred to the tendon. It is evident that a need
      exists for specific study of muscular response during impact. More microanalysis
      of the impact phase needs to be conducted specifically for the one-handed
      backhand groundstroke.

PMID- 7712558
TI  - Elbow injuries.
AB  - Injuries about the elbow are common in racquet sports. Lateral epicondylitis is
      seen most often, but symptoms can arise from other sources including the medial
      elbow and the articular surfaces themselves. Medial elbow symptoms can result
      from medial epicondylitis, medial collateral ligament injury, ulnar nerve trauma,
      or any combination of these injuries. Careful evaluation of medial elbow pain is
      required to define the causes. Proper technique, conditioning, and equipment are
      also important in reducing the risk of injury to the elbow.

PMID- 7712556
TI  - Exercise training for tennis.
AB  - Tennis is a physically demanding sport. A complete conditioning program designed
      to address both the demands of the sport and the individual player's
      musculoskeletal base is important in tennis, particularly at the competitive
      junior and professional levels. Recreational players can certainly use
      conditioning to improve their level of performance, but the primary concern in
      this group is general fitness development and injury prevention. In the junior
      player, physical development should begin with a sound program for physical
      fitness, including flexibility, cardiorespiratory endurance, general strength,
      and muscular endurance. Once a sound fitness base has been developed, the
      competitive junior players should progress to conditioning for sport specific
      movements and for injury prevention. At the elite level, tennis players should
      have previously developed a sound general physical fitness base. These players
      can then spend a greater percentage of their conditioning time on athletic
      fitness and sport specific movement training, as well as injury prevention. By
      addressing all of the components of a total body conditioning program, the
      possibility of peak performance of the individual tennis player is enhanced.

PMID- 7712559
TI  - Biomechanical analysis of the shoulder during tennis activities.
AB  - Biomechanical analysis of the shoulder in tennis is still in early stages;
      however, the available data do allow some conclusions and some recommendations
      for conditioning, evaluation, and rehabilitation. Normal shoulder biomechanical
      function requires an intact kinetic chain to create the energy, produce the
      forces and stabilize the joint in tennis activities. Only through this mechanism
      can optimum performance with minimal injury risk be maintained. Conditioning of
      the shoulder for tennis should take this into account. Exercises should involve
      force generation by the large leg and trunk muscles, scapular stabilization, and
      closed chain co-contraction activity for the shoulder stabilizers. Similarly,
      clinical evaluation for shoulder problems must include assessment of areas
      distant to the shoulder. Kinetic chain failure can cause extra stress on the
      shoulder, causing or exacerbating clinical symptoms at the shoulder. Clinical
      evaluation of shoulder joint structures also is enhanced by knowledge of the
      integration of the constraint systems, and the fact that more than one system may
      be involved in shoulder pathology. Finally, rehabilitation efforts for shoulder
      problems need to focus on allowing functional return of the shoulder joint in the
      context of the entire kinetic chain of tennis specific activity. Rehabilitation
      of all areas of kinetic chain failure, such as trunk inflexibility or
      scapulothoracic dyskinesis, should be undertaken in conjunction with
      rehabilitation techniques for the shoulder. The sports medicine clinician will
      have a more functional framework for assessing shoulder activity and injury in
      tennis through the understanding of these biomechanical principles.

PMID- 7712560
TI  - Rehabilitation of shoulder and elbow injuries in tennis players.
AB  - Optimization of treatment of the tennis player with an upper extremity overuse
      injury requires a thorough understanding and analysis of the biomechanical and
      physiologic stresses inherent in the game of tennis. Anatomic adaptations found
      in the upper extremity of elite tennis players provide the framework for
      evaluation and treatment of overuse injury through both an anatomically based
      total-arm strength program and efforts to normalize joint arthrokinematics.
      Integration of these key factors allows the clinician to rehabilitate the patient
      and design preventive conditioning programs in a scientifically based, sport
      specific manner.

PMID- 7712561
TI  - [Nitric oxide--its role in CNS physiology (the status of knowledge up to mid
      1994)].

PMID- 7712562
TI  - [Regeneration of peripheral nerves after injury--review].

PMID- 7712564
TI  - [Models of heart function mechanics. II. Mathematical models of left ventricular
      systole].

PMID- 7712563
TI  - [Models of heart function mechanics. I. Past and present mathematical models of
      the left heart ventricle].

PMID- 7712565
TI  - [Models in modern neurophysiology].

PMID- 7712566
TI  - New scientific terms in basic medical sciences.

PMID- 7712567
TI  - [The operational control studies of smear positive tuberculosis cases with short
      course chemotherapy under the full-course management and supervision].
AB  - Two groups of smear positive ambulatory tuberculous patients were treated with
      the regimen of 2H2R3E3Z3/4H3R, 189 and 192 cases received full-management and
      full-course supervision respectively and the smear conversion rates at the
      completion of treatment are 98.9% and 96.9%. This suggests that it can get equal
      rate of successful chemotherapy with the standard full-course management compared
      with the full-course supervision.

PMID- 7712568
TI  - [Evaluation of BCG vaccination programme based on results of the Third Nationwide
      Tuberculosis Survey].
AB  - Evaluation of BCG vaccination programme had been carried out by means of re
      analyzing the results of the Third Nationwide Random Sampling Survey for
      Epidemiology of Tuberculosis conducted in 1990. The BCG vaccination coverage
      among children under 4 years was 65.0% in 1990. It was lower than other reports
      in the past. The positive rate of tuberculin testing among children under 4 years
      who had the history of BCG vaccination was only 26.3%. City had the highest rate
      of 55.8%. The fact indicated the unsatisfactory quality of BCG vaccination in the
      country. The factors inducing such a lower positive rate should be clarified and
      overcome as soon as possible in the near future. The protective effect of BCG
      vaccination for children under 4 years was apparent but it was not in 5-9 age
      group. In this connexion, the investigation and study on the necessity of re
      vaccination among primary school entrants should be conducted.

PMID- 7712569
TI  - [Polymerase chain reaction for the diagnosis of tuberculous pleural effusion].
AB  - Polymerase chain reaction was applied to detect DNA of mycobacterium tuberculosis
      in 62 patients with pleural effusion, and result of PCR was compared with those
      of conventional procedures. It was found that in 34 tuberculous pleural effusion,
      the positive rates of pleural effusion acid-fast staining, culture and PCR was
      5.9%, 8.8% and 52.9%, respectively. The sensitivity of PCR was much higher than
      those of acid-fast staining and culture (all P < 0.01). The results of acid-fast
      staining and culture in 28 non-tuberculous effusion were negative, there were,
      however, 4 PCR positive results within this group (14.3%). Our results suggested
      that for the diagnosis of mycobacterium tuberculosis PCR is a rapid, sensitive
      and specific procedure. Some factors that affected the results of PCR were
      discussed.

PMID- 7712570
TI  - [Clinical significance of increased serum soluble interleukin-2 receptor levels
      in patients with pulmonary tuberculosis].
AB  - The serum soluble interleukin-2 receptor (sIL-2R) was measured in 40 patients
      with pulmonary tuberculosis by using sandwich enzyme linked immunosorbent assay.
      The results show that the levels of sIL-2R in sera of the various stage patients
      are markedly higher than that of the normal controls and the serum levels of sIL
      2R were associated significantly with the patients' conditions. These findings
      suggest that sIL-2R may be an useful referential indicator for diagnosing,
      monitoring and predicting pulmonary tuberculosis.

PMID- 7712571
TI  - [Clinical significance of soluble interleukin-2 receptor in patients with
      pulmonary tuberculosis].
AB  - The levels of soluble interleukin-2 receptor (sIL-2R) among patients with various
      pulmonary diseases were measured by using sandwich ELISA. The levels of sIL-2R
      were significantly elevated in patients with active pulmonary tuberculosis and
      acute pneumonia when compared with healthy controls. The concentrations of sIL-2R
      in patients with active pulmonary tuberculosis decreased in accordance with
      improvement of other laboratory parameters. The clinical significance and
      possible mechanism of increasing of sIL-2R in patients with pulmonary
      tuberculosis were discussed.

PMID- 7712572
TI  - [Detection of Mycobacterium tuberculosis using a nested-primer gene amplification
      assay].
AB  - A nested-primer gene amplification assay (NPGAA) was established by using two
      pairs of primers, an outside pair of primers and an inside pair of primers,
      sequences of which were from M. tuberculosis(Mtb) gro EL genes. The outside pair
      of primers should amplify a 576-bp piece of the Mtb gro EL gene that contains
      sites for the inside pair of primers, which should amplify a 344-bp piece. The
      results shows NPGAA'S detectable limitation was 1 organism/ml and no
      amplification products were produced from DNAs of other mycobacterium species
      tested in this study. For detecting Mtb, the entire NPGAA, from sample
      preparation to data analysis, can be completed within 6-8 hours. When identifying
      AFB cultures isolated from lesions of skin diseases, the same positive size
      patterns were obtained.

PMID- 7712574
TI  - [Levels of VIIIR:Ag, VIII:C and fibrinogen in plasma of patients with lung
      cancer].
AB  - Levels of VIIIR: Ag, VIII: C and fibrinogen (Fbg) in plasma have been measured in
      80 patients with primary lung cancer. The results demonstrate that the plasma
      levels of VIIIR: Ag, VIII:C and Fbg in patients with lung cancer increase
      significantly in comparison with normal control group (P < 0.001). The levels
      increase along with the disease progressing. After treatment, all the three
      levels have decreased in treatment effective group. It is concluded that the
      measurements of plasma levels of VIIIR: Ag, VIII:C and Fbg are important in
      judging the condition of patients, to prognose and instruct the treatment for
      patients with lung cancer.

PMID- 7712573
TI  - [Quantitative analysis of cellular morphometry and DNA content measurement of
      experimental lung adenocarcinoma].
AB  - This article reported the image analysis of normal epithelia of bronchi (group
      1), hyperplasia epithelia (group 2), atypical hyperplasia epithelia (group 3) and
      adenocarcinoma (group 4) of the lung in the hamsters induced by tin mine dust and
      chimney dust in Yunnan Tin Min CO. 16 parameters were observed and compared. Each
      value was tested by stepwise discriminational classification and an accuracy rate
      of 95% was reached. DNA ploidy was investigated, and no case of > 5C cell was
      found in normal and hyperplasia group. Severe atypia had a lower percentage,
      (4.00%) and lung adenocarcinoma was characterized by a high percentage of > 5C
      cell (10.75%), A significant difference was shown between the percentage of > 5C
      cell of severe atypia and that of adenocarcinoma. Significantly different (P <
      0.01).

PMID- 7712576
TI  - [Molecular degradation forms of plasma fibronectin in patients with chronic
      obstructive pulmonary disease].
AB  - In order to explore the molecular degradation forms of plasma fibronectin (Fn) in
      patients with chronic obstructive pulmonary disease (COPD) and its clinical
      value. We measured the concentration of plasma Fn and analysed Fn molecular
      forms. The results suggested that the increase of Fn degradation is one of the
      causes of plasma Fn decline in patients with COPD. The obvious correlations were
      found between the extent of Fn degradation and the severity of the disease. In
      view of the documented influences of Fn fragments on the host defense, the
      increase of Fn fragments in plasma of COPD patients may be an additional factor
      of inflammatory amplification loops and more contributing to the decrease of
      plasma opsonic activity.

PMID- 7712575
TI  - [Clinical analysis of 60 cases of nosocomal pneumonias].
AB  - This article gives a clinical analysis upon 60 cases of nosocomial acquired
      pneumonia. All the patients are > 18 years old and the onset time ranged from 3
      to 180 days after they were hospitalized with an average of 38.77 days, mostly 30
      days after admission (27 cases, 49%). Among the primary diseases, the hematologic
      disorder (18 cases, 30%) rank the first, followed by cerebrovascular disease (9
      cases, 15%) and connective tissue disease (8 cases, 13.3%), The common inducing
      factors are the using of corticosteroids and chemotherapy (34 cases, 58%),
      tracheotomy and tracheal cannula (7 cases, 11.6%). Fever occurs in 96% of the
      patients and cough 63.3%. The positive rate of sputum bacterial culture is
      95.46%. Pseudomonas aeruginosa isolated in 25 cases (56.8%). and Klebsiella
      pneumoniae 18 cases (40%). P. aeruginosa shows resistant to the third generation
      of cefalosporins more than before, and is sensitive to ciprofloxacin and
      polymyxin B, while K. pneumoniae is resistant to many kinds of antibiotics,
      especially ampicilline and carbenicilline. The death rate of infection of P.
      aeruginosa is 58.33% (14/25) and that of K. pneumoniae is 60% (12/18), that of
      mixed infection is 66.67% (16/23).

PMID- 7712577
TI  - [Clinical application of ultra-thin bronchofiberscope examination].
AB  - Ultra-thin bronchofiberscope examination has been performed in 73 persons
      including normal persons and patients with various bronchopulmonary disease. The
      main lesions of peripheral airways revealed by the examination were reddening,
      pigmentation, secretion, engorgement of blood vessels, mucosal pallor and edema.
      The result points out that this is a valuable new technique in the diagnosis of
      small airway lesions, especially the diffused inflammatory of small airways. In
      case of a localized lesion, because of the difficulty to precisely determine the
      site, the effectiveness of this examination is limited. We also briefly discussed
      the matters that one should pay attention to while performing this technique.

PMID- 7712578
TI  - [High frequency electrical knife through fibrobronchoscope in the treatment of
      tracheal cancer with large airway obstruction].
AB  - From May 1985 to December 1991, high frequency electrical knife (HFEK) through
      fibrobronchoscope was used to treat the large airway obstruction by tracheal
      cancers in 11 patients (cystic adenoid carcinoma: 8 squamous cell carcinoma: 2
      and undifferentiated small cell carcinoma: 1). Most of the tracheal cancer
      patients were inoperable because of extensive lesions or poor lung function.
      Olympus BF B3R or BF 10 Type Fibrobronchoscope, Olympus UES or Olympus PSD-10
      high frequent electricity producer with a home-made electrical knife were
      applied. After 53 times of HFEK treatment of tracheal cancer, all patients showed
      remarkable improvement in lung function and exertional dyspnea. CONCLUSION: HFEK
      is valuable in relieving dyspnea in patients with large airway obstruction with
      tracheal cancer. After endoscopic cautery to release the obstruction, it is
      necessary to use radiotherapy and chemotherapy for the patients to get better
      results.

PMID- 7712579
TI  - [Surgical treatment and diagnosis of adult bronchogenic cysts].
AB  - Between 1974 and 1993, 22 adults with bronchogenic cysts were operated in our
      hospital: 14 men and 8 women, ranging from 11 to 62 years old. The location was
      mediastinal in 13 (59.1%) and intrapulmonary in 9 (40.9%). Cysts were symptomatic
      (chest pain and recurrent bronchiolitis) in 20 patients (91%). The perioperative
      complications include infection in lungs and in the cysts and dysphagia due to
      esophageal compression. Chest pain was the main symptom in mediastinal cyst and
      recurrent infection of lungs in intrapulmonary cysts. Plain chest radiographs
      showed round shadows. Occasional air-fluid levels, peripheral calcification may
      be found. Operation is the best method for treating cysts. All cysts were
      completely excised. No perioperative, late complication or recurrence developed
      in our patients. Operation was recommended in most instances to confirm the
      diagnosis, to relieve symptoms, and to prevent complications.

PMID- 7712580
TI  - [The influence of endothelin to the airway tract of guinea pig and its
      relationship to the asthma].
AB  - In order to find the relationship between endothelin and asthma, we investigated
      the level of plasma endothelin of guinea pigs with asthma, and the
      bronchoconstriction of endothelin to the guinea pigs. We also measured the plasma
      concentration of PGE2 TXB2 PGF2 alpha LTC4 after using ET intravenously. The
      results showed that the level of plasma endothelin elevated significantly in
      guinea pigs with asthma. The bronchoconstriction was positively related to the
      dosage of endothelin intravenously. PLA2 antagonist and cyclooxygenase inhibitor
      can reduce the bronchoconstriction caused by endothelin. All these indicated that
      endothelin may contribute to the cause of asthma.

PMID- 7712581
TI  - [Clinical significance of the chemiluminescence (CL) of polymorphonuclear (PMN)
      and lymphocyte (LY) in bronchial asthma].
AB  - In the patients with bronchial asthma, the chemiluminescence (CL) of
      polymorphonuclear (PMN) and lymphocyte (LY) in blood had two peaks, maximal peak
      value decreased and peak time prolonged: cAMP, cAMP/cGMP, SOD in plasma
      decreased, IgE increased. The authors suggest that the pathogenetic mechanism of
      bronchial asthma may related to activated inflammatory cells, released mediators
      and inbalanced immuno opsonic functions.

PMID- 7712582
TI  - [Characteristics of hypoxic ventilatory response in Tibetan living at moderate
      and high altitudes].
AB  - Hypoxic and exercises ventilatory responses measured in Tibetan who lived at
      moderate (2000-3000m, M-Tibetan) and high (4000-4700m, H-Tibetan) altitude areas.
      The result showed that the slope of hypoxic ventilatory response (HVR; VE/SaO2)
      in M- and H-Tibetan was 0.81 +/- 0.07 and 0.46 +/- 0.04 L/min/%SaO2 (P < 0.01)
      and the maximal exercise ventilation (VEmax) was 78.3 +/- 3.5 and 68.2 +/- 2.1
      L/min (P < 0.05), respectively. There were positive correlation between delta
      VE/delta SaO2 and VEmax, which gamma = 47.0 +/- 37.3x, r = 0.70 in M-Tibetan, and
      gamma = 53.8 +/- 31.4x, r = 0.67 in H-Tibetan. Maximal heart rate of the H
      Tibetan was significantly lower than that in the M-Tibetan (P < 0.01). It is
      suggested that the attenuation of HVR depends on the magnitude of the hypoxic
      stimulus. Therefore, there are differences even among the high-altitude natives
      in ventilatory response to hypoxia, e.g. normal respiratory sensitivity to
      hypoxia in moderate-altitude natives, and blunted in high-altitude natives.

PMID- 7712583
TI  - [Report of 2 cases of extrinsic allergic alveolitis and review of relevant
      literature].
AB  - Two cases of extrinsic allergic alveolitis were reported. The antigens inducing
      the immunologic events are wheat powder, hair-dye liquid. The pathology, symptoms
      and chest radiograph features were presented. The best treatment is avoidance of
      antigen exposure and to use of corticosteroids. The chronic form of the disease
      often leads to irreversible pulmonary interstitial fibrosis.

PMID- 7712584
TI  - [The protective effects of cilazapril of chronic hypoxic pulmonary hypertension
      and hypoxemia in rats].
AB  - This study attempted to research the protective effects of cilazapril, a new ACE
      inhibitor, on chronic hypoxic pulmonary hypertension and hypoxemia in rats. The
      mean pulmonary arterial pressure (mPAP) of the rats after hypoxia and injection
      with 1% Fecl3 via the tail veins for 4 weeks increased significantly but its PaO2
      decreased separately. Cilazapril effectively protected mPAP increase and PaO2
      decrease in rats treated with Cilazapril (0.5 mg/d) by suppressing the lung
      injury of TNF and oxygen free radical.

PMID- 7712586
TI  - Overview of articles on eicosanoids and cancer.

PMID- 7712585
TI  - [Comparative effects of calcium channel blockers and L-arginine on chronic
      intermittent hypoxic pulmonary hypertension in rats].
AB  - Experiments were carried on rats to study the preventive effects of calcium
      channel blockers Nitrendipine, Nifedipine and L-Arginine (L- Arginine is the
      physiological precursor of nitric oxide in endothelium-dependent relaxation) on
      chronic intermittent hypoxia induced pulmonary hypertension, on the right
      ventricular hypertrophy and pulmonary vascular pathologic changes. The results
      showed (1) Nitrendipine, Nifedipine and L-arginine played significant role in
      preventing chronic hypoxic pulmonary hypertension and the right ventricular
      hypertrophy. (2) There was no significant difference between Nitrendipine,
      Nifedipine and L- arginine in preventing hypoxic pulmonary hypertension (P >
      0.05). (3) Nitrendipine was better than Nifedipine in reducing the hypoxic
      pulmonary hypertension.

PMID- 7712587
TI  - Regulation of prostaglandin synthase-1 and prostaglandin synthase-2.
AB  - It has been assumed that the rate-limiting step in the ligand-induced synthesis
      of prostaglandins is the release of arachidonic acid from membrane phospholipid
      stores as a result of the activation of phospholipase. The assumption has been
      that the arachidonic acid is converted to PGH2 by the constitutive prostaglandin
      synthase/cyclooxygenase EC1.14.99.1 (PGS-1) enzyme present in cells. In this
      model, PGS-1 is proposed to be present in excess, and the production of
      arachidonic acid is thought to be rate limiting. However, a second prostaglandin
      synthase gene, PGS-2 has recently been described. The PGS-2 gene is induced by a
      variety of ligands, in cells as diverse as fibroblasts, monocytes, macrophages,
      smooth muscle cells, ovarian granulosa cells, epithelial cells, endothelial
      cells, and neurons. Moreover, PGS-2 induction is inhibited in nearly all contexts
      by glucocorticoids. It seems likely, therefore, that the regulation of PGS-2
      expression plays a critical role in the production of prostanoids, both in normal
      physiological processes and in pathophysiological processes involving these
      paracrine mediators. In this review, we consider the regulation of the two genes,
      PGS-1 and PGS-2, that encode the isoforms of prostaglandin synthase.

PMID- 7712588
TI  - Regulation of leukotriene biosynthesis.
AB  - Leukotrienes are products of arachidonic acid metabolism derived through the
      action of the 5-lipoxygenase enzyme pathway. Leukotriene B4 has been implicated
      as a mediator of inflammation through induction of leukocyte and lymphocyte
      activation. The cysteinyl leukotrienes are important mediators of immediate
      hypersensitivity reactions and initiate smooth muscle contraction. Regulation of
      the production of leukotrienes can be achieved either through the action of
      direct 5-lipoxygenase inhibitors or indirect leukotriene biosynthesis inhibitors
      which bind to 5-lipoxygenase activating protein. Leukotriene C4 synthase and
      leukotriene A4 hydrolase represent alternative enzymic targets within the
      biosynthetic cascade. Leukotriene receptor antagonists also have important
      therapeutic possibilities and in particular, leukotriene D4 receptor antagonists
      have shown utility in the treatment of human bronchial asthma.

PMID- 7712589
TI  - Aspirin, NSAIDs, and digestive tract cancers.

PMID- 7712590
TI  - Sulindac and polyp regression.
AB  - Sulindac is useful in regression of adenomatous polyps. In addition to orally
      administered sulindac, rectal preparations also appear to be efficacious [32].
      However, further studies are necessary to determine whether regression of
      adenomas, the precursor of colorectal cancer, will cause decrease in colorectal
      cancer risk in both FAP and non FAP patients. Moreover, clinical studies are
      needed to test the application of this potential chemopreventative drug in
      several other patient populations. Several interesting observations have been
      made concerning the use of sulindac. Indomethacin, a related NSAID to sulindac,
      did not cause polyp regression. Also, upper gastrointestinal tract polyps in the
      stomach and duodenum appear not to be affected by sulindac therapy. These
      observations might be explained by the metabolism of sulindac in which the
      pharmacologically active sulfide metabolite is generated and distributed in the
      large intestine. Also, investigators noted that after discontinuation of sulindac
      adenomas recurred. Sulindac treatment was well tolerated at the usual clinical
      doses. Although some investigators have speculated on the effect of prostaglandin
      inhibition sulindac on cAMP-dependent mechanisms which control cellular
      proliferation [33], the cause of adenoma regression is unknown. There is evidence
      that colorectal endogenous prostaglandin levels decrease with sulindac.
      Evaluation of colorectal mucosal cellular proliferation in patients treated with
      sulindac has revealed a decrease in labelling index by bromodeoxyuridine labeling
      in one study [28] but no change in labelling index by [3H]thymidine incorporation
      in another investigation [34]. Also, ki 67 labelling index, another measure of
      cellular proliferation, was not affected in the colorectal mucosa of patients
      taking sulindac.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712591
TI  - Chemoprevention of colon cancer by dietary fatty acids.
AB  - During the last two decades, substantial progress has been made in the
      understanding of the relationship between the dietary constituents and
      development of colon cancer in man. Unlike studies of cancer among smokers and
      nonsmokers, nutritional epidemiologic studies are confronted with the inherent
      difficulty of assessing reasonably precise exposures. The lack of consistency
      between international correlation studies and case-control studies does not
      necessarily negate a dietary etiology of colon cancer because these
      inconsistencies may have arisen, at least in part, from methodological
      limitations. Some of these deficiencies in epidemiological studies of diet and
      cancer have been corrected; recent case-control studies demonstrated that high
      dietary fat is a risk factor for colon cancer development and that an overall
      increase in intake of foods high in fiber might decrease the risk for colon
      cancer. The results of epidemiologic studies may be assumed to present
      conservative estimates of the true risk for cancer associated with diet. The
      populations with high incidence of colon cancer are characterized by high
      consumption of dietary fat, which may be a risk factor in the absence of factors
      that are protective, such as whole-grain cereals and of other high-fiber.
      Laboratory animal model studies have shown that certain dietary lipids and fibers
      influence tumorigenesis in the colon. The data of metabolic epidemiological and
      laboratory animal model studies are sufficiently convincing with respect to
      enhancement of colon cancer by type of fat and protection by certain dietary
      fibers.

PMID- 7712592
TI  - Generation of mutagens during arachidonic acid metabolism.

PMID- 7712593
TI  - Preclinical studies of antitumor prostaglandins by using human ovarian cancer
      cells.
AB  - Pleiotropic actions of antitumor prostaglandins (PGs) on tumor cells are reviewed
      including our preclinical results focused on human ovarian cancer. Regarding
      inhibition of cell proliferation, antitumor PGs exerts its action as a G1
      blocking agent. The cyclopentenone PGs inhibit myc oncogene expression while
      inhibiting the cell cycle progression and results in apoptotic cell death and
      growth inhibition. Cyclopentenone PGs inhibit growth of various tumors
      transplanted to mice or nude mice and show adjuvant effects to cis
      diamminedichloroplatinum(II) (CDDP). In order to elucidate a role of antitumor
      PGs in immune systems, relevance of effects on tumor growth with those on the
      immune systems are also discussed with our results.

PMID- 7712594
TI  - Modulation of mitogenesis by liver fatty acid binding protein.
AB  - Liver fatty acid binding protein (L-FABP), a cytoplasmic 14 kDa protein
      previously termed Z protein, is conventionally considered to be an intracellular
      carrier of fatty acids in rat hepatocytes. The following evidence now indicates
      that L-FABP is also a specific mediator of mitogenesis of rat hepatocytes: a. the
      synergy between the action of L-FABP and unsaturated fatty acids, especially
      linoleic acid, in the promotion of cell proliferation; b. the specific
      requirement for L-FABP in induction of mitogenesis by two classes of nongenotoxic
      hepatocarcinogenic peroxisome proliferators (amphipathic carboxylates and
      tetrazole-substituted acetophenones); c. the direct correlation between the
      binding avidities of different prostaglandins for L-FABP and their relative
      growth inhibitory activities toward cultured rat hepatocytes; d. the temporal
      coincidences between the covalent binding to L-FABP by chemically reactive
      metabolites of the genotoxic carcinogens, 2-acetylaminofluorene and aminoazo
      dyes, and their growth inhibitions of hepatocytes during liver carcinogenesis in
      rats; e. and f. the marked elevations of L-FABP in rat liver during mitosis in
      normal and regenerating hepatocytes, and during the entire cell cycle in the
      hyperplastic and malignant hepatocytes that are produced by the genotoxic
      carcinogens, 2-acetylaminofluorene and aminoazo dyes. These actions of L-FABP are
      consistent with those of a protein involved in regulation of hepatocyte
      multiplication. Discovery that L-FABP, the target protein of the two types of
      genotoxic carcinogens, is required for the mitogenesis induced by two classes of
      nongenotoxic carcinogens points to a common process by which both groups of
      carcinogens promote hepatocyte multiplication. The implication is that during
      tumor promotion of liver carcinogenesis, these genotoxic and nongenotoxic
      carcinogens modify the normal process by which L-FABP, functioning as a specific
      receptor of unsaturated fatty acids or their metabolites, promotes the
      multiplication of hepatocytes.

PMID- 7712596
TI  - Prostacyclin and its analogues: antimetastatic effects and mechanisms of action.
AB  - More than a decade ago, prostacyclin, a dienoic bicyclic eicosanoid derived from
      the metabolism of arachidnoic acid, was found to possess potent inhibitory
      effects on tumor cell metastasis. Thereafter, several laboratories demonstrated
      the metastasis-suppressive activity of prostacyclin in a wide spectrum of tumor
      types. Due to the short half-life of prostacyclin, researchers have focused on
      looking for stable prostacyclin analogues which have extended half lives and
      increased bioavailabilities. Cicaprost, among other prostacyclin analogues
      tested, has been demonstrated, like prostacyclin, to effectively inhibit
      metastasis in several different animal models (i.e., both experimental and
      spontaneous metastasis models). Prostacyclin as well as cicaprost prevent not
      only hematogenous, but also lymphatic metastasis. Furthermore, these compounds
      also inhibit the growth of established micrometastases after removal of the
      primary tumors. Mechanistic studies revealed that the antimetastatic effects of
      prostacyclin and its analogues are more related to their interference with tumor
      cell-host interactions (such as tumor cell induced platelet aggregation, tumor
      cell adhesion to endothelial cells and subendothelial matrix, tumor cell induced
      endothelial cell retraction, etc.) than their direct inhibition of the growth of
      primary tumors. The potent and widespread metastasis-retarding effects of
      prostacyclin and its stable analogues in animal tumor models warrant their
      clinical trial in treating human cancer patients and preventing metastasis.

PMID- 7712598
TI  - Cellular proliferation and lipid metabolism: importance of lipoxygenases in
      modulating epidermal growth factor-dependent mitogenesis.
AB  - In this article we have reviewed and discussed the results of our investigation
      of lipid metabolites as modulators of epidermal growth factor (EGF) signaling
      pathways. We have studied epidermal growth factor-dependent mitogenesis in BALB/c
      3T3 and Syrian hamster embryo (SHE) cells in culture. We observed that EGF
      stimulates the formation of prostaglandins in BALB/c 3T3 cells and their
      formation appears to be necessary for EGF dependent mitogenesis. EGF did not
      stimulate PGE2 formation in SHE cells and in fact, exogenously added PGE2
      inhibited mitogenesis. In both cell lines, EGF stimulated the formation of
      lipoxygenase-derived 13(S)-hydroxyoctadecadienoic acid (13-HODE) and inhibition
      of 13-HODE formation attenuated mitogenesis. The addition of 13-(S)-HODE enhanced
      EGF-dependent mitogenesis but when added alone, the compound was not mitogenic.
      Other metabolites, including lipoxygenase metabolites of arachidonic acid, were
      either weak simulators of EGF-dependent mitogenesis or essentially inactive. The
      13(S)-HODE appears to be formed by an apparently unique lipoxygenase that is
      regulated by the tyrosine kinase activity of the EGF receptor. The mechanisms by
      which lipids, particularly the lipoxygenase-derived linoleic acid metabolites,
      modulate the EGF signaling pathways leading to cell proliferation is discussed.
      The possible significance of lipoxygenase and prostaglandin H synthase-dependent
      metabolism of unsaturated fatty acids in breast and colon cancer is also
      discussed.

PMID- 7712595
TI  - Eicosanoids and the immunology of cancer.
AB  - Studies in both cancer patients and in animal tumor models have shown that immune
      defenses can mediate destruction of tumor, but these defenses are often
      functioning at a suppressed or suboptimal level. Frequently, prostaglandins,
      mainly PGE2, have been implicated in this tumor-associated subversion of immune
      function, with immune reactivities to tumor typically being enhanced by
      prostaglandin synthesis inhibitor. Both the tumor and tumor-induced host immune
      suppressive macrophages have the capacity to suppress immune functions through
      their production of PGE2. Although the inhibitory functions have been more widely
      studied, recent evaluations of the effects of PGE2 have led to the surprising
      realization that not all of the PGE2's effects are inhibitory to immune function.
      Summarized below are some of the well characterized inhibitory effects of PGE2,
      as well as the lesser studied stimulatory effects of PGE2 toward the effector
      cells that are considered to be important in the immune defense against cancer.

PMID- 7712601
TI  - Antimicrobial efficacy of two commercial RGP contact lens care systems.
AB  - We compared the antimicrobial activities of two rigid gas permeable (RGP) lens
      care systems, a one-step wetting and soaking system (0.005% chlorhexidine
      gluconate, 0.02% EDTA) and a conditioning solution (0.006% chlorhexidine
      gluconate, 0.05% EDTA). The formulations were individually inoculated with
      approximately 10(6) CFU/mL of a pathogenic organism. Both the one-step wetting
      and soaking system and the conditioning solution demonstrated good antimicrobial
      efficacy against Pseudomonas aeruginosa, Staphylococcus epidermidis, Serratia
      marcescens, and Aspergillus fumigatus. However, the one-step wetting and soaking
      system provides better disinfection against Candida albicans (1.2 log reduction
      in 4 hours) than the conditioning solution (0.39 log reduction in 4 hours). The
      one-step system also reduced S. marcescens by 5 logs in 1 hour, whereas the
      conditioning solution reduced S. marcescens by about 2 logs only in the same time
      interval. Although both RGP lens care systems use the same active preservative
      (chlorhexidine digluconate), the variation in disinfecting activities may be
      attributed to differences in formulation and buffer systems.

PMID- 7712600
TI  - A quantitative and qualitative assessment of the Solitaire Bifocal Contact Lens.
AB  - We performed qualitative and quantitative assessments of contact lens performance
      at 1 and 6 months among 23 patients enrolled in the Solitaire Bifocal Contact
      Lens Study. Overall satisfaction and comfort at 6 months was rated good to
      excellent in 83% and 84% of patients, respectively. Daytime acuity at distance
      and near were rated very good to excellent in 75% and 83% of subjects.
      Quantitative measurements of distance and near acuities at 1 month revealed 83%
      and 88% of subjects, respectively, seeing better than or equal to 20/25 or J1. At
      6 months there was a moderate decrease in the measured distance acuity. A
      disparity in glare disability was noted, with 53% of subjects indicating
      significant glare problems but only 21% of glare tested patients having acuities
      worse than 20/40. Attrition from the study was highest in the first month and was
      more common among first-time contact lens users. Overall, this segmented bifocal
      contact lens is well-tolerated and provides good distance and near vision for
      presbyopic patients.

PMID- 7712602
TI  - The effect of Acanthamoeba concentration on adherence to four types of unworn
      soft contact lenses.
AB  - Contact lens wear is a predominant risk factor for Acanthamoeba keratitis. The
      exact nature of the relationship between organism concentration and contact lens
      adherence is poorly understood. We investigated the effect of Acanthamoeba
      inoculation concentration on adherence to four categories of contact lenses of
      varying polymers and water content. Acanthamoeba polyphaga was harvested in log
      growth phase at 5 days subculture and suspended in PBS at concentrations of 1 x
      10(2), 10(3), 10(4), 10(5), and 10(6) organisms/mL (trophozoite:cyst ratio 90:10
      +/- 2). Sterile unworn polymacon, etafilcon, lidofilcon, and bufilcon contact
      lens segments were exposed to Acanthamoeba for 2 hours. Acanthamoeba adherence
      was quantified using phase contrast microscopy. For all lens types, trophozoite
      adherence increased as the concentration of inoculum increased, but the
      relationship was not directly proportional. In all cases the minimal adherence
      was observed at 10(2). Trophozoite adherence increased disproportionate to cysts
      for all contact lens types. The greatest adherence was to lidofilcon lenses. At
      all concentrations adherence was greater to lidofilcon than etafilcon or
      polymacon, and greater to bufilcon than etafilcon or polymacon at the P < 0.01
      level. Adherence was significantly greater to lidofilcon than bufilcon only at 1
      x 10(5) and 10(6); P < 0.05 (ANOVA). This study suggests that adherence of A.
      polyphaga to contact lenses increases with the number of organisms in the
      inoculum, but the relationship is not directly proportional. The number of
      adherent organisms varies by contact lens type, with the greatest adherence to
      lidofilcon and the least to etafilcon lenses.

PMID- 7712597
TI  - 12-lipoxygenases and 12(S)-HETE: role in cancer metastasis.
AB  - Arachidonic acid metabolites have been implicated in multiple steps of
      carcinogenesis. Their role in tumor cell metastasis, the ultimate challenge for
      the treatment of cancer patients, are however not well-documented. Arachidonic
      acid is primarily metabolized through three pathways, i.e., cyclooxygenase,
      lipoxygenase, and P450-dependent monooxygenase. In this review we focus our
      attention on one specific lipoxygenase, i.e., 12-lipoxygenase, and its potential
      role in modulating the metastatic process. In mammalian cells there exist three
      types of 12-lipoxygenases which differ in tissue distribution, preferential
      substrates, and profile of their metabolites. Most of these 12-lipoxygenases have
      been cloned and sequenced, and the molecular and biochemical determinants
      responsible for catalysis of specific substrates characterized. Solid tumor cells
      express 12-lipoxygenase mRNA, possess 12-lipoxygenase protein, and biosynthesize
      12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid], as revealed by numerous
      experimental approaches. The ability of tumor cells to generate 12(S)-HETE is
      positively correlated to their metastatic potential. A large collection of
      experimental data suggest that 12(S)-HETE is a crucial intracellular signaling
      molecule that activates protein kinase C and mediates the biological functions of
      many growth factors and cytokines such as bFGF, PDGF, EGF, and AMF. 12(S)-HETE
      plays a pivotal role in multiple steps of the metastatic 'cascade' encompassing
      tumor cell-vasculature interactions, tumor cell motility, proteolysis, invasion,
      and angiogenesis. The fact that 12-lipoxygenase is expressed in a wide diversity
      of tumor cell lines and 12(S)-HETE is a key modulatory molecule in metastasis
      provides the rationale for targeting these molecules in anti-cancer and anti
      metastasis therapeutic protocols.

PMID- 7712603
TI  - Ulcerative keratitis from overnight contact lens wear compared with other life
      risks.
AB  - Wearers of extended wear contact lenses are at increased risk for ulcerative
      keratitis compared with daily wear contact lens users. Using incidence rates, we
      compared ulcerative keratitis in contact lens wear with other diseases and
      serious life risks. "Comparative risk," a theoretical construct for this paper,
      is a framework through which the incidence rates are compared. Although the risks
      of ulcerative keratitis in extended wear are greater than with daily wear contact
      lenses, the risks of extended soft contact lens wear are 2-10 times less than the
      risks for non-fatal, serious and disruptive occurrences in a general population.
      Contact lens associated ulcerative keratitis is in the range of 10-20 times
      greater than the incidence of common causes of death in a low risk, middle-age
      population.

PMID- 7712605
TI  - Development of a new soft gas permeable contact lens with Dk 300.
AB  - The effects on the rabbit cornea of a new gas permeable nonhydrophilic soft
      contact lens made of newly designed polymer with a Dk value of 300 were studied
      physiologically, histologically, and histochemically during 5 days of daily wear
      followed by 14 days of extended wear. Corneal swelling was observed to be within
      10% of corneal thickness during the wear period. No serious corneal surface
      changes were observed. Specular microscopy showed no endothelial changes in terms
      of cell density, coefficient of variation of cell area (CV), or hexagonality
      before and 2 weeks after lens wear. Histochemical study using periodic acid
      Schiff staining and histological study with hematoxylin-eosin revealed no
      remarkable changes. Scanning electron microscopy revealed slight focal changes;
      there were no significant changes. The results show that the new soft gas
      permeable contact lens has no harmful effect on the rabbit cornea.

PMID- 7712607
TI  - Corneal topographic changes after refitting polymethylmethacrylate contact lens
      wearers into rigid gas permeable materials.
AB  - Polymethylmethacrylate (PMMA) contact lenses can alter corneal shape and induce
      corneal warpage or distortion. The purpose of our study was to determine the
      effects on the corneal topography after immediate refitting of long-term PMMA
      contact lens wearers into rigid gas permeable (RGP) materials. Six eyes with
      contact lens induced corneal warpage from PMMA contact lenses were assessed using
      the Topographical Mapping System-1. Statistical analysis was performed for the
      following variables prior to and approximately 6 months after contact lens
      refitting: best spectacle visual acuity, manifest refraction, surface regularity
      index, surface asymmetry index, keratometry, and simulated keratometry. Best
      spectacle visual acuity improved an average of 1.8 +/- 1.0 (mean +/- SD, P <
      0.05) lines of Snellen visual acuity, while refraction did not change
      appreciably. The surface regularity index diminished by 0.51 +/- 0.32 (P = 0.01).
      The surface asymmetry index improved by 0.32 +/- 0.26 (P < 0.05). There was a
      good correlation between keratometry and simulated keratometry, and neither
      changed significantly after refitting with RGP contact lenses. All general
      topographic patterns remained unchanged throughout the study. Immediate refitting
      of long-term PMMA contact lens wearers into RGP materials of similar fit allows a
      slightly more regular and symmetric central corneal shape, which can result in
      improved spectacle visual acuity. The general corneal topographic patterns of
      contact lens induced corneal warpage did not change or improve after refitting to
      RGP material.

PMID- 7712609
TI  - 3-D computer models of human keratocytes.
AB  - We constructed three separate three-dimensional (3-D) models from serial high
      voltage electron micrographs (HVEM) of five human keratocytes. The serial
      micrographs were digitized using HVEM-3D software and a digitizing tablet on a
      personal computer system. After the models were constructed, we added surface and
      volume data using another computer program, SYNU. Hard copies of selected
      orientations of the model were obtained with a laser printer, by color
      photographs of the computer monitor, by direct imaging from the computer file, or
      by video recording. The first model was constructed from 73 serial sections of
      two activated keratoconus keratocytes next to a break in Bowman's layer (BL). Two
      adjacent keratocytes from the same cornea, but located away from disruptions in
      BL, made up the second model. The third model was created from approximately 106
      serial sections of a normal human keratocyte cultured in an attached collagen
      gel. Examination of these 3-D models created from HVEM micrographs showed
      striking differences in keratocyte morphology and cell/matrix interactions
      related to corneal disease.

PMID- 7712608
TI  - Computerized videokeratoscopy contact lens software for RGP fitting in a
      bilateral postkeratoplasty patient: a clinical case report.
AB  - Computerized videokeratoscopy systems now allow interactive rigid gas permeable
      (RGP) fitting evaluation using fluorescein pattern simulations through updated
      software programs. We used Computed Anatomy's Topographic Modeling System-1 (TMS
      1) Custom Design Contact Lens Program successfully to refit a symptomatic
      bilateral post-penetrating keratoplasty patient. No trial lenses were used. For
      each eye the base curve, optic zone size, and edge lift were chosen from the
      optimal fluorescein pattern designed and titrated on the TMS-1 unit. Lens powers
      were based on the patient's previous lenses and overrefraction. Dispensed lenses
      provided a clinically acceptable fit, good comfort, and maximal visual acuity,
      and no adjustments were necessary. Corneal videokeratoscopy can be successfully
      employed to titrate an RGP fit, even on irregular corneas.

PMID- 7712604
TI  - Identification of fungi growing within soft contact lenses: a report from the
      neotropics.
AB  - We isolated and identified 17 fungi within the matrix of 17 soft contact lenses
      (SCLs). This work was done in a neotropical location where climatic conditions
      favor year-round fungal growth. The fungi identified belong to eight genera, four
      of which have not previously been found contaminating the surface or the matrix
      of SCLs.

PMID- 7712606
TI  - Clinical performance of a spline-based apical vaulting keratoconus corneal
      contact lens design.
AB  - We refit 68 eyes with keratoconus and recurring contact lens induced apical
      corneal erosions with rigid corneal contact lenses having computer-generated
      spline curves. This junctionless design incorporates two independently
      configurable fitting zones on the back surface of the lenses that enable them to
      fit most keratoconus eyes with an apical vault rather than the traditional two or
      three point touch. Apical staining was eliminated in 49 eyes (72%), significantly
      reduced in 13 eyes (19%), and remained unchanged in six eyes (9%). Corneal
      abrasion related symptoms of contact lens wear intolerance resolved in 41 of 43
      eyes.

PMID- 7712610
TI  - Effect of diclofenac sodium (Voltaren) on hypoxia-induced corneal edema in
      humans.
AB  - We evaluated the effect of diclofenac sodium (Voltaren) drops on patients with
      hypoxia-induced corneal edema. Thirty age- and sex-matched subjects were randomly
      assigned to one of three groups. Members of each group received masked solutions
      of either Voltaren, Voltaren vehicle, or a non-preserved lubricant (Cellufresh)
      every 6 hours for 24 hours and then hourly for 2 hours immediately prior to
      inducing corneal edema in the experimental eye. Bilateral ultrasonic pachymetry
      was performed prior to applying a thick contact lens and light patch on the
      experimental eye of all subjects for 3 hours. The fellow eye served as the
      control. Following lens removal, bilateral corneal thickness was measured every
      30 minutes. The percentage change in corneal swelling for each subject and group
      was calculated. The findings were also normalized to the control eye to minimize
      diurnal and individual variability. The results were plotted both as percentage
      change from hour 0 and percentage change normalized to the control eye. Corneal
      swelling ranged from 9-11% in all 3 groups, with recovery at 2-3 hours. No
      significant difference was found among the three groups (P > 0.05, ANOVA). There
      was a slight trend toward reduced thickness in the Cellufresh group, but this was
      not statistically significant. Voltaren does not appear to have an effect on the
      hypoxia-induced corneal edema associated with the production of arachidonic acid
      pathway metabolites.

PMID- 7712611
TI  - The use of rigid gas permeable contact lenses in scarred corneas.
AB  - Perforating corneal injuries often result in scarred corneas in which adequate
      visual rehabilitation cannot be achieved with spectacles due to irregular corneal
      surface. In these eyes, the presence of aphakia often adds to the problem with
      the coexistence of anisometropia. In this study, rigid gas permeable (RGP)
      contact lenses were fit in 33 post-traumatic scarred corneas of 33 patients.
      Twenty-seven of the 33 eyes (82%) were successfully fit without complications for
      an average follow-up of 19.3 months. The success rate was observed to be lower
      (50%) for patients less than 10 years old, whereas it was 100% in patients older
      than 20 years. The six failures included two eyes with amblyopia and
      unsatisfactory visual acuity, two eyes in two patients who lacked motivation to
      use contact lenses, and two eyes that were contact lens intolerant. There was no
      significant correlation between the failure groups and the location and size of
      the corneal scar. The only contact lens related complication was punctate
      epithelial keratitis in three of the 33 eyes (9%). The results of this study
      indicate that RGP contact lenses are successful in the majority of patients (82%)
      with post-traumatic scarred corneas, especially in the adult age group, and may
      obviate corneal surgery in these patients.

PMID- 7712599
TI  - Regulation of protein kinase C and role in cancer biology.
AB  - Protein kinase C (PKC) is a family of closely related lipid-dependent and
      diacyglycerol-activated isoenzymes known to play an important role in the signal
      transduction pathways involved in hormone release, mitogenesis and tumor
      promotion. Reversible activation of PKC by the second messengers diacylglycerol
      and calcium is an established model for the short term regulation of PKC in the
      immediate events of signal transduction. PKC can also be modulated long term by
      changes in the levels of activators or inhibitors for a prolonged period or by
      changes in the levels of functional PKC isoenzymes in the cell during development
      or in response to hormones and/or differentiation factors. Indeed, studies have
      indicated that the sustained activation or inhibition of PKC activity in vivo may
      play a critical role in regulation of long term cellular events such as
      proliferation, differentiation and tumorigenesis. In addition, these regulatory
      events are important in colon cancer, where a decrease in PKC activators and
      activity suggests PKC acts as an anti-oncogene, in breast cancer, where an
      increase in PKC activity suggests an oncogenic role for PKC, and in multidrug
      resistance (MDR) and metastasis where an increase in PKC activity correlates with
      increased resistance and metastatic potential. These studies highlight the
      importance and significance of regulation of PKC activity in vivo.

PMID- 7712612
TI  - Excimer laser phototherapeutic keratectomy for corneal diseases: a follow-up
      study.
AB  - We performed phototherapeutic keratectomy (PTK) in 39 eyes of 38 patients with
      various corneal diseases. Patients were divided into four diagnostic entities:
      group 1 consistent of 11 eyes with postinfectious or posttraumatic corneal scars;
      15 eyes with various corneal dystrophies or keratopathies comprised group 2;
      group 3 consisted to two eyes with recurrent corneal erosion; and 11 eyes with
      either primary or recurrent pterygia composed group 4. Postoperative follow-up
      ranged from 3 to 15 months (mean: 9 months). The goals of PTK (visual
      improvement, ocular comfort, or visibility for cataract extraction) were set
      individually for each patient and were achieved in 19 of 38 eyes (50%); one
      patient was lost to follow-up. Preoperatively, best corrected visual acuity
      improved two or more Snellen lines in nine of 31 eyes (29%). Both cases of
      recurrent corneal erosions were successfully treated. One eye lost two Snellen
      lines because of increased irregular astigmatism after PTK. In two eyes, corneal
      decompensation was observed 1 month after the operation, but no other serious
      complications were observed. The excimer laser was combined with surgical
      abrasions or use of topical EDTA, with good results. The excimer laser is a
      valuable tool for treating anterior corneal irregularities. It can also be
      combined with existing surgical methods. However, results can be improved with
      better patient selection criteria and by evaluating PTK on the basis of visual
      expectations and type and location of corneal pathology.

PMID- 7712613
TI  - Acanthamoeba keratitis.
AB  - The incidence of Acanthamoeba keratitis has decreased significantly, and it is no
      longer a reportable condition in the United States. Corneal abrasion and contact
      lenses play an important role in the development of Acanthamoeba keratitis. One
      of the most important features of the disease is severe pain, which is atypical
      for herpes simplex. The pathognomonic sign for Acanthamoeba is radial neuritis or
      inflammation around the corneal nerve caused by the parasites. The most important
      step in prevention of Acanthamoeba keratitis is effective education of patients
      about the care of contact lenses. A combination of Brolene and Neomycin is the
      best approach in treating Acanthamoeba keratitis. However, if treatment with
      these drugs fails, clotrimazole is recommended.

PMID- 7712614
TI  - Contact lens type, material, and deposits and giant papillary conjunctivitis.
AB  - Giant papillary conjunctivitis (GPC) is a condition commonly encountered in
      clinical practice. Much research has taken place aimed at more clearly
      understanding the pathogenesis of GPC. We review the current literature and
      discuss the association between GPC and contact lens type, material, and
      deposits.

PMID- 7712615
TI  - Pathology of AIDS-related liver disease.
AB  - Hepatomegaly and abnormalities of serum liver tests are common problems in
      patients with acquired immune deficiency syndrome. Opportunist infections
      (Mycobacterium avium-intracellulare and cytomegalovirus) and neoplasms (lymphoma,
      Kaposi's sarcoma) are among the most prevalent hepatic lesions in AIDS. Although
      Kupffer cells and endothelial cells are potential sites of human immunodeficiency
      virus 1 (HIV-1) infection, current studies do not indicate that the liver is a
      major reservoir for this virus. Drug hepatotoxicity, multimicrobial infections of
      the biliary tree resembling sclerosing cholangitis and a variety of nonspecific
      hepatic changes should be considered in evaluating AIDS patients or HIV-1
      infected patients with evidence of liver dysfunction.

PMID- 7712616
TI  - Primary biliary cirrhosis.
AB  - Primary biliary cirrhosis is a chronic, usually progressive, cholestatic liver
      disease of presumed autoimmune etiology that affects predominantly young and
      middle-aged women. It is nearly always associated with an antibody directed
      against a component of the pyruvate dehydrogenase complex located on the inner
      wall of the mitochondria. The disease is associated with a number of other
      associated autoimmune disorders. No totally effective medical treatment has been
      established for the disease, although urosdeoxycholic acid appears promising.
      Complications of cholestasis such as fat malabsorption and fat-soluble vitamin
      deficiency should be excluded or corrected when found. Individual patient
      prognosis varies. Several models for estimating individual patient survival are
      available. Liver transplantation is recognized as a procedure to extend and
      improve the quality of life for patients with advanced disease.

PMID- 7712617
TI  - Bioavailability of alcohol: role of gastric metabolism and its interaction with
      other drugs.
AB  - In most individuals, only part of the imbibed alcohol reaches the systemic blood.
      With doses relevant to social drinking, this is due mainly to gastric first-pass
      metabolism of alcohol, which acts as a barrier against toxic alcohol blood
      levels. The activity of gastric alcohol dehydrogenase can account for a
      substantial fraction of this metabolism. Fasting, female gender, old age,
      dilution of alcoholic beverages, chronic alcohol consumption and still
      undetermined factors decrease the gastric metabolism of alcohol. Aspirin and some
      H2-receptor antagonists also inhibit this gastric activity. In subjects with
      documented first-pass metabolism, these drugs increase blood alcohol levels,
      especially after repeated small drinks, and may result in unexpected impairment
      to perform complex tasks, such as driving. Thus, patients treated with these
      drugs should be warned of this possible side effect.

PMID- 7712618
TI  - Placebo and placebo effect: their impact on the evaluation of drug response in
      patients.
AB  - Placebo, defined as any therapeutic procedure, without any specific activity,
      given deliberately to have an effect on a patient, symptom, syndrome or disease,
      has a great impact in the evaluation of drug response. The possible pathways via
      which the possible effect brings about clinical and physiological changes remain
      unknown, but a humoral mechanism seems to be implicated in some placebo effects
      (e.g. placebo-induced analgesia). The placebo effect depends on many factors,
      including the type of patient, the personality of the physician, the doctor
      patient relationship and the type and even the colour of the drug preparation.
      Placebo control is important particularly when the disease is characterized by
      frequent spontaneous periods of acute exacerbation and remission. Functional
      (such as dyspepsia and irritable bowel syndrome) and organic (such as peptic
      ulcer and inflammatory bowel disease) gastrointestinal diseases have got great
      benefit from placebo-controlled clinical trials. In such trials the more
      effective the placebo is, the more difficult it will be to demonstrate the
      efficacy of active drug in statistical terms. Nevertheless, provided the use of
      placebo be ethical for a given condition, placebo-controlled trials are the only
      objective way of assessing correctly drug response in patients.

PMID- 7712619
TI  - Mitochondrial genes and neurological disease.

PMID- 7712620
TI  - Basilar artery occlusion following yoga exercise: a case report.
AB  - Basilar artery occlusion developed in a 34 year old woman 2 months after adopting
      unusual neck postures during yoga practice. On angiography, her basilar artery
      was filled with intraluminal clot while the vertebral arteries were normal. We
      postulate that a severe reduction in blood flow and possibly an intimal tear
      triggered thrombosis of the vertebral artery and that the final stroke mechanism
      was artery-to-artery embolism.

PMID- 7712621
TI  - Pentoxifylline in the treatment of acute ischaemic stroke--a reappraisal in
      Chinese stroke patients.
AB  - A double-blind, randomized and placebo-controlled trial was conducted on 110
      Chinese patients with ischaemic stroke who were stratified into 2 subtypes
      (cortical and lacunar infarcts) according to their clinical and CT findings.
      Treatment was started within 36-48 hours after the stroke onset. Pentoxifylline
      was administered intravenously in a dose of 600 mg daily for 5 days, together
      with oral aspirin 150 mg daily. Neurological deficits were scored on admission
      and at one week. Demographic data were comparable between the treatment and
      placebo groups. For cortical infarcts, there were significantly more patients in
      the placebo group who deteriorated and died than in the treatment group (p <
      0.02). As for the lacunar infarcts, there was no difference between groups in the
      numbers of patients who improved or deteriorated. Our study shows that the
      positive effect of pentoxifylline can be demonstrated only in patients with
      cortical infarction. Early deterioration and mortality were significantly
      decreased in these patients. The clinical course of lacunar infarction was not
      affected by pentoxifylline. It is not clear whether aspirin may potentiate the
      antiplatelet function of pentoxifylline and contribute to its temporary clinical
      efficacy in this way.

PMID- 7712622
TI  - Single photon emission computed tomography in intractable infantile seizures.
AB  - We aimed to determine the site of ictal foci and the pathogenesis of seizures in
      4 infants with intractable seizures. The patients were studied using simultaneous
      video and electroencephalographic (EEG) monitoring, structural studies and ictal
      and interictal single photon emission computed tomography (SPECT). Ictal
      neurophysiology showed multifocal seizure propagation in Patients 1 and 2 and
      generalised abnormal electrical patterns in Patients 2, 3 and 4. Magnetic
      resonance imaging (MRI) demonstrated a focal abnormality in Patient 4. SPECT
      studies showed focal or multifocal increased uptake in 3 subjects (Patients
      1,3,4) and increased uptake in the thalamic and basal ganglia regions of 2
      subjects (Patients 2,3). SPECT studies contributed to an understanding of the
      pathogenesis of seizure initiation and propagation in the 4 patients studied.

PMID- 7712623
TI  - Plasma vigabatrin enantiomer ratios in adults and children.
AB  - The new anticonvulsant vigabatrin (gamma-vinyl-gamma-aminobutyric acid) is
      normally supplied as a racemate, but its anticonvulsant effect is thought to
      reside in its [S]-enantiomer only. The plasma concentration ratio of the [R] to
      [S] enantiomers appears to remain constant across the vigabatrin dosage interval
      in adult volunteers, and in the present study this has also proved to be the case
      in 12 chronically treated adult epileptic patients. However, in 8 epileptic
      children chronically treated with other anticonvulsants and given add-on
      vigabatrin therapy because of failure to control seizures, plasma [R]:[S]
      vigabatrin ratios changed across the drug dosage interval, the [R]-vigabatrin
      levels tending to be relatively higher soon after intake, and to fall more
      rapidly than the [S]-vigabatrin concentrations over the next few hours (mean half
      lives 2.52 +/- SD 0.49 and 6.53 +/- SD 6.62 hours). The reason for the shorter
      half-life of [R]-vigabatrin in children remains to be elucidated, but it appears
      that measurement of racemic vigabatrin plasma concentrations in children, though
      not in adults, may lead to somewhat misleading conclusions as regards the amount
      of the circulating anticonvulsant [S]-vigabatrin.

PMID- 7712624
TI  - Apparent hydrocephalus and chronic multiple sclerosis: a report of two cases.
AB  - Generalised ventricular dilatation with or without cerebral atrophy is common in
      longstanding multiple sclerosis. This has been widely assumed to be due to
      periventricular white matter atrophy rather than true communicating hydrocephalus
      although it can be difficult to distinguish between these on radiological
      grounds. Here we report 2 chronic MS patients who had progressive dementia, gait
      disturbance and urinary incontinence and in whom neuroimaging, and in one case
      CSF infusion studies, suggested hydrocephalus. Both significantly improved
      following shunting procedures. We suggest that further study is required to
      investigate whether a significant proportion of patients with chronic MS and
      dilated ventricles have shunt-responsive hydrocephalus.

PMID- 7712625
TI  - The explosive Copula of Thomas Willis.
AB  - Thomas Willis (1621-1675), arguably the founding father of neurology, devised an
      interpretation of neurophysiology which involved motor function being mediated by
      explosions in nerve tissue and muscle, facilitated by the temporary development
      of an explosive Copula comprising short-lived aggregates of 'nitrous' and
      'sulphur' particles i.e. the components of gunpowder. Seen from a modern
      standpoint, such a concept is manifestly absurd. However, seen from the
      standpoint of the Paracelsian iatrochemistry to which Willis subscribed, and
      understood in the spirit of analogy which he probably intended, Willis'
      interpretation can be regarded as the beginning of the application of
      bioenergetics to neural function.

PMID- 7712626
TI  - Motor neuropathies and antiglycolipid antibodies.
AB  - This paper describes patients with demyelinating motor neuropathies associated
      with conduction blocks, pure motor neuropathies and intermediate forms with
      resemblances to amyotrophic lateral sclerosis, in persons with raised titres of
      anti-GM1 antibodies. The specificity of the abnormal anti-GM1 antibody titres is
      discussed, and the possibilities of immunosuppressive therapy mentioned.

PMID- 7712627
TI  - Motor nerve biopsy: feasibility and safety.
AB  - Motor nerve biopsy was attempted on 19 occasions in 18 patients. Nerve tissue was
      obtained in 16. The nerves biopsied included those to the anconeus (4 times),
      palmaris longus (6), flexor sublimus (1), triceps (2), extensor carpi radialis
      (1), quadriceps (1) and gastrocnemius (1). Attempts to biopsy the radial nerve,
      the nerve to plantaris and the left common peroneal nerves failed in 2 patients.
      The lengths of nerve obtained varied from 1 to 3 cm, and from 1-5 fasciculi were
      present in the specimens. Sufficient material for both electron microscopy and
      teasing was present in 11. No patient experienced increased weakness, but one had
      transient paraesthesiae in the distal forearm following biopsy of the nerve to
      the palmaris longus. We conclude that motor nerve biopsy as described is both
      feasible and safe. The nerve to the palmaris longus, where that muscle was
      present, provided the optimum specimen for pathological studies.

PMID- 7712628
TI  - The role of skin nociceptive afferent nerves in blister healing.
AB  - Because sensory neuropeptides improve survival of critical skin and muscle flaps
      in rats, skin nociceptive sensory nerve function in blister healing was examined.
      Sensory nerve ablation by unilateral hindlimb denervation or cutaneous axon
      reflex enhancement by 14 days systemic nicotine treatment (5 mg kg-1 day-1)
      decreased and increased, respectively, peripheral motor functions of nociceptive
      (peptidergic) skin nerves. Effects on nociception were measured by a radiant heat
      tail-flick test. Axon reflex flares were evoked by transdermal iontophoresis of
      acetylcholine or noxious electrical stimulation under pentobarbitone 40 mg kg-1
      anaesthesia. Resultant changes in cutaneous microvascular blood flux were
      measured non-invasively by laser Doppler flowmetry. In nicotine-treated rats
      compared with placebo-treated controls, acetylcholine-evoked axon reflex flare
      was enhanced by 240% (p < 0.01) without enhancement of electrically evoked flare.
      Thus, nicotine-sensitized nociceptors show stimulus specificity in their
      enhancement of neurogenic flare responses. No significant changes were seen in
      other endothelial-dependent or smooth muscle-dependent microvascular dilator
      responses. Nicotine-treated rats had prolonged tail-flick withdrawal latencies to
      noxious radiant heat stimuli compared with placebo-treated controls (p < 0.05),
      suggesting an antinociceptive or analgesic effect of nicotine-treatment.
      Neurogenic effects on wound healing rate were assessed by measuring the
      dimensions of standardized blisters twice daily. The blisters were raised on
      hindpaw glabrous skin using a constant weight and diameter of compressed dry ice
      pellet applied for 30 secs at constant force. Dry-ice blisters raised on the
      hindpaw 14 days post-denervation were significantly slower to heal completely (42
      days) than controls (30 days: P < 0.05) and the surrounding inflammation was
      reduced. By contrast, nicotine-treated rats showed more rapid blister healing (25
      days) than controls (30 days), seen only in the later phase after day 15.
      Finally, resting substance P release from blisters, after direct cutaneous nerve
      stimulation, appears to be enhanced in nicotine-treated rats. Thus nociceptive
      innervation appears critical for inflammation and rapid healing of blisters in
      rat skin. The data signal a possible important role for neuropeptides in these
      processes and question the function of nicotinic receptors on sensory nerves.

PMID- 7712629
TI  - Kennedy's disease: clinical presentation and laboratory diagnosis.
AB  - Kennedy's disease is a form of progressive spinal and bulbar muscular atrophy of
      adult onset. This paper describes a case of Kennedy's disease and discusses the
      laboratory diagnosis and the underlying genetic mechanism. Three other
      neurological diseases, Huntington's disease, myotonic dystrophy and fragile X
      syndrome, which have similar genetic defects, are also discussed.

PMID- 7712630
TI  - Orthostatic tremor (shaky legs syndrome).
AB  - Nine patients (mean age 73 years: range 62-83 years) are described with a
      characteristic tremor or instability of the trunk and lower limbs which occurred
      when standing still, and which was either diminished or abolished by walking.
      Three had essential tremor of the upper limbs. The duration of the disorder
      ranged between 4 months and 20 years (mean 5 years). In all cases the condition
      worsened with time. Eight patients responded to clonazepam (0.5 to 2.0 mg per
      day) and one to chlordiazepoxide (30 mg per day). Orthostatic tremor is a
      disabling condition that responds to benzodiazepine treatment and may be more
      frequent than previously recognised.

PMID- 7712631
TI  - Acute myopathy in status asthmaticus.
AB  - An acute myopathy complicating life-threatening asthma has been reported with
      increasing frequency. We present a further 3 patients with this complication.
      Each patient had nerve conduction studies, electromyography and muscle biopsy
      performed. The records of a cohort of 12 patients, ventilated in an intensive
      care unit over a 16 month period, were reviewed. Eleven out of the 12 patients
      developed an elevated creatine kinase level (median 1311 U/L, range 185-9973 U/L)
      and 4 developed symptomatic weakness. The myopathy of status asthmaticus is not a
      homogeneous clinicopathological entity. Although myopathy is the predominant
      feature, there is a neuropathic component in some patients. Full recovery is
      usual. The combination of corticosteroids and neuromuscular blocking agents has
      been proposed as the possible cause of the complication.

PMID- 7712632
TI  - Watershed cerebral infarction associated with perioperative hypotension.
AB  - The pathogenesis of perioperative stroke is not clear from the literature. To
      explore the influence of various risk factors we examined the clinical, Duplex
      ultrasound and computerised tomography findings of all cases suffering cerebral
      infarction within 24 hours of surgery in a prospective series of 358 coronary or
      peripheral vascular reconstructive operations. Four patients (1.1%) had cerebral
      infarcts within 24 hours of surgery, all associated with perioperative systolic
      blood pressures of less than 90 mmHg. The other significant risk factor was
      previous cerebral ischaemic symptoms. Haemodynamic cerebral ischaemia occurred
      immediately after operation in 2 of 10 cases with severe symptomatic carotid
      stenosis or occlusion (stroke risk 20%; 95% confidence interval 2.52%-55.61%).
      Two cases with mild carotid disease had cerebral infarcts in previously
      asymptomatic hemispheres following coronary artery bypass graft surgery. One of
      these had clinical and computerised tomographic evidence of cortical watershed
      infarction. We conclude that cerebral haemodynamics are important in
      perioperative stroke and that symptomatic patients with severe carotid disease
      may be at high risk of perioperative watershed infarction.

PMID- 7712633
TI  - Regional cerebral blood flow during memory recognition and neuropsychological
      performance in patients referred for investigation of dementia.
AB  - Regional cerebral blood flow was studied at rest and during a memory recognition
      activation task in a preliminary investigation carried out in patients with mild
      to moderate dementia of Alzheimer type and in 2 control groups of subjects. There
      were differences in the sites of activation-increased blood flows between the
      normal controls and the controls with major depression, while the Alzheimer's
      disease subjects showed more variable patterns of flow response, which differed
      overall from those present in the 2 control groups.

PMID- 7712634
TI  - EEG monitoring during angiographic balloon test carotid occlusion: experience in
      sixteen cases.
AB  - Ipsilateral hemispheric ischaemia related to permanent or temporary arterial
      occlusion at the time of operation is a potential risk of surgery upon some
      aneurysms or tumours which involve the internal carotid artery. Presurgical
      evaluation of the risks of temporary or permanent internal carotid artery
      occlusion may help predict patients in these circumstances at risk of stroke.
      Balloon test occlusion studies involve the elective preoperative occlusion of the
      internal carotid artery by a deflatable balloon inserted into the cerebral
      circulation under angiographic control. We have performed 16 balloon test
      occlusion studies; 2 subjects developed clinical and electroencephalographic
      changes when the carotid artery was temporarily occluded, and these changes
      reverted to normal when the balloon was deflated. The results of the test
      occlusion studies helped in planning the surgical management of all the subjects
      involved.

PMID- 7712635
TI  - Ataxia-telangiectasia.
AB  - Ataxia-telangiectasia is a complex syndrome that includes a very high cancer risk
      in children with a progressive cerebellar ataxia, the onset of which occurs in
      early infancy. Ocular telangiectasiae often do not appear until several years
      after the ataxia. The most common type of malignancy is lymphoma, usually of the
      B-cell type. Leukemias also occur. Failure to diagnose ataxia-telangiectasia in
      an infant with lymphoma or leukemia may result in radiation therapy with
      conventional dosages, which is contraindicated in ataxia-telangiectasia patients.

PMID- 7712636
TI  - Neurofibromatosis.
AB  - The neurofibromatoses are defined by the presence of cafe-au-lait macules and
      neurofibromas and are associated with central and peripheral nervous system
      tumors. Individuals with neurofibromatosis 1 are at risk for optic nerve gliomas,
      nerve root and plexi neurofibromas and schwannomas, spinal cord tumors, benign
      and malignant peripheral nerve sheath tumors, and pheochromocytomas. Individuals
      with neurofibromatosis 2 are at risk for presenile cataracts, vestibular
      schwannomas, intracranial and intraspinal meningiomas, and intramedullary spinal
      cord ependymomas.

PMID- 7712637
TI  - Nevoid basal cell carcinoma syndrome.
AB  - Nevoid basal cell carcinoma syndrome has as its hallmarks such diverse
      manifestations as numerous cutaneous basal cell cancers and epidermal cysts,
      palmar and plantar pits, keratocysts of the jaw, calcified dural folds, various
      skeletal anomalies, cleft lip and/or palate, and various other neoplasms or
      hamartomas. Inheritance is autosomal dominant. The etiology of all of the above
      findings appears to be a mutation in a tumor suppressor gene that also plays a
      role in normal embryonic development.

PMID- 7712638
TI  - Peutz-Jeghers syndrome.
AB  - Peutz-Jeghers syndrome is inherited as an autosomal dominant trait with variable
      incomplete penetrance. Patients with Peutz-Jeghers syndrome characteristically
      have hamartomatous polyps throughout their entire gastrointestinal tract,
      particularly in the small bowel, and mucocutaneous hyperpigmentation involving
      the lips, oral cavity, and skin. Although the intestinal hamartomatous polyps
      have a lower incidence of malignant change in the gastrointestinal tract than do
      adenomatous polyps, recent information suggests that the overall neoplastic
      transformation from Peutz-Jeghers syndrome is not a rare event.

PMID- 7712640
TI  - Rothmund-Thomson syndrome.
AB  - Rothmund-Thomson syndrome is a rare inherited disorder characterized by
      poikilodermatous skin changes that appear in infancy. The inheritance is
      autosomal recessive. Patients exhibit variable features including skeletal
      abnormalities, juvenile cataracts, and a higher-than-expected incidence of
      malignancy. This article describes aspects of the inheritance, the incidence of
      characteristic features, and the malignant potential of Rothmund-Thomson
      syndrome. Insight into its origin is provided through a review of the clinical
      signs and symptoms, the in vitro studies of endocrine function, and the reported
      DNA repair abnormalities.

PMID- 7712639
TI  - The porphyrias and hepatocellular carcinoma.
AB  - Hepatocellular carcinoma probably represents the final step of the effects of the
      various precipitating agents for porphyria cutanea tarda, such as alcohol, drugs,
      hormones, and hepatitis C infection. Risk factors associated with its development
      include male gender, age over 50 years, liver fibrosis or cirrhosis, and a long
      history (over 10 years) of symptomatic porphyria cutanea tarda.

PMID- 7712641
TI  - Tuberous sclerosis.
AB  - Tuberous sclerosis complex is a disorder of cellular differentiation and
      proliferation that is inherited as an autosomal dominant trait with variable
      penetrance and a high spontaneous mutation rate. Lesions occur in the brain,
      skin, kidneys, heart, and other organs. Recent studies suggest genetic
      heterogeneity, with at least two gene loci on chromosomes 9, 16, and perhaps 11.

PMID- 7712642
TI  - Werner's syndrome.
AB  - Werner's syndrome is a rare autosomal recessive disorder that affects connective
      tissue throughout the body. The genetic basis is not yet known, although many
      laboratory abnormalities have been reported. The manifestations are widespread,
      and many organs may prematurely undergo changes usually associated with aging.
      The disease generally becomes apparent around puberty, with growth arrest and
      thinning and graying of hair. Rapidly progressing bilateral cataracts typically
      occur when patients are in their 20s and 30s. A dermatologist may be consulted
      because of the scleroderma-like appearance of the skin, lower-extremity ulcers or
      calluses, thinning and graying of hair or baldness, nail dystrophy or loss,
      wrinkling and aging of the face, or skin cancers. Patients should have a thorough
      clinical and laboratory work-up, keeping in mind their elevated risk for
      neoplasms.

PMID- 7712643
TI  - Xeroderma pigmentosum.
AB  - Xeroderma pigmentosum is a rare, recessively transmitted disease associated with
      increased sensitivity to ultraviolet radiation in wavelengths found in sunlight,
      development of cancers in sun-exposed areas of the body in much larger numbers
      and much earlier in life than in normal individuals, and in some patients,
      neurologic deficiencies unrelated to sun exposure. Extensive cellular,
      biochemical, and molecular genetic studies in numerous laboratories have revealed
      that cells derived from patients with this disease have defective repair of
      ultraviolet-light-induced damage in cellular DNA, and that extensive genetic
      heterogeneity and numerous distinct genes are involved in the genetics of this
      disease and the etiopathogenesis of its associated changes. A number of these
      genes and gene products are now being, or have been, cloned, and their gene
      products characterized.

PMID- 7712644
TI  - The Carney complex (myxomas, spotty pigmentation, endocrine overactivity, and
      schwannomas).
AB  - The Carney complex is a multisystem tumorous disorder that features myxomas
      (heart, skin, and breast), spotty skin pigmentation (lentigines and blue nevi),
      endocrine tumors (adrenal, testicular, and pituitary), and peripheral nerve
      tumors (schwannomas). The condition is transmitted as an autosomal dominant
      trait. The most serious components of the syndrome are cardiac myxoma and
      psammomatous melanotic schwannoma. The cutaneous manifestations are a major clue
      to the disorder.

PMID- 7712645
TI  - Miscellaneous genodermatoses: Beckwith-Wiedemann syndrome, Birt-Hogg-Dube
      syndrome, familial atypical multiple mole melanoma syndrome, hereditary tylosis,
      incontinentia pigmenti, and supernumerary nipples.
AB  - Beckwith-Wiedemann syndrome, familial atypical multiple mole melanoma syndrome,
      and hereditary tylosis are bona fide genodermatoses with malignant potential.
      Each of these conditions is associated with an increased incidence of certain
      tumors: Wilms' tumor, adrenocortical carcinomas, pancreatoblastomas, and
      hepatoblastomas in Beckwith-Wiedemann syndrome; intraocular malignant melanoma,
      pancreatic carcinoma, and noncolorectal gastrointestinal cancers in familial
      atypical multiple mole melanoma syndrome; and squamous cell carcinoma of the
      esophagus in hereditary tylosis. Other cancer-related genodermatoses are Birt
      Hogg-Dube syndrome (associated with medullary carcinoma of the thyroid and renal
      cell carcinoma) and its variant, Hornstein-Knickenberg syndrome (associated with
      colon carcinoma). Kidney tumors (Wilms' tumor and malignant rhabdoid tumor),
      leukemias (acute myelogenous and acute myelomonocytic), retinoblastoma, and
      paratesticular rhabdomyosarcoma have been reported recently in children with
      another genodermatosis-incontinentia pigmenti. Supernumerary nipples (polythelia)
      may be sporadic or familial in occurrence; their presence has been associated
      with an increased incidence of renal adenocarcinoma, testicular cancer, prostate
      cancer, and urinary bladder carcinoma. The general characteristics, mucosal and
      skin manifestations, and noncutaneous features of all these conditions are
      reviewed. Also, the associated malignancies of these genodermatoses and other
      conditions that are characterized by dermatologic manifestations and may be
      either familial or secondary to an inherited gene defect are summarized.

PMID- 7712646
TI  - Treatment of skin diseases in HIV-infected patients.
AB  - Skin diseases are common in HIV-infected patients. Although some of the cutaneous
      manifestations of HIV-infection resemble more severe forms of common skin
      diseases, as with seborrheic dermatitis and psoriasis, the response to standard
      treatment is not as expected. Indeed, this may be the clue that leads the
      clinician to suspect underlying HIV infection. In addition, hitherto undescribed
      skin diseases have been seen in the HIV-infected population, for many of which
      treatment has been discovered serendipitously. It is important for both the
      dermatologist and the patient to recognize that many of the cutaneous
      manifestations of HIV infection are difficult to treat because of the underlying
      immunosuppression. It may not be possible to "cure" a skin disease, but the goal
      in these cases is to make the patient as comfortable as possible by providing
      symptomatic relief. Often, imagination is required of the practitioner to find
      the treatment that will make the patient more comfortable. With patience and
      determination, the dermatologist can help most patients with HIV-related skin
      disease.

PMID- 7712647
TI  - Cowden syndrome (multiple hamartoma syndrome).
AB  - Cowden syndrome (multiple hamartoma syndrome) is characterized by multiple facial
      papules, gingival papillomas, acral keratoses, and other hamartomatous lesions.
      There is a high incidence of breast and thyroid carcinoma. Recognition of this
      syndrome may lead to the early diagnosis of cancer.

PMID- 7712648
TI  - Dyskeratosis congenita.
AB  - Dyskeratosis congenita is a rare genodermatosis. Malignant deterioration and
      hematologic complications are well-described features of this syndrome. Correct
      recognition is essential for proper management. A review of diagnostic
      considerations and treatment guidelines is presented.

PMID- 7712650
TI  - Gardner's syndrome.
AB  - Gardner's syndrome is an autosomal dominant genodermatosis. Familial polyposis of
      the colon, osteomas, and cutaneous epidermoid cysts are characteristic features.
      Colon cancer will develop in all affected individuals unless prophylactic
      colectomy is performed. The follow-up and management of patients with Gardner's
      syndrome require a coordinated effort by physicians with expertise in
      gastroenterology, general surgery, oral surgery, radiology, endocrinology,
      neurology, ophthalmology, and dermatology. Genetic and psychological counseling
      should also be available for these patients.

PMID- 7712649
TI  - Fanconi anemia.
AB  - Fanconi anemia is a phenotypically and genotypically heterogeneous syndrome in
      which patients manifest various congenital abnormalities, bone marrow failure,
      and predisposition to malignancy. The primary dermatologic manifestations are
      pigmentation abnormalities (hyperpigmentation, hypopigmentation, cafe-au-lait
      spots) and cutaneous malignancies. The gene for one of the complementation groups
      (FACC) has been cloned, and the gene product has been shown to have a cytoplasmic
      localization, ruling out a direct role for the Fanconi anemia gene in DNA repair.
      A better understanding of the function of the FACC polypeptide, and the cloning
      of genes for the other Fanconi anemia complementation groups, should lead to a
      better understanding of the basic problems of birth defects and cancer
      predisposition and the interaction of genetic and epigenetic factors in the
      pathogenesis of these problems.

PMID- 7712651
TI  - HLA-linked hemochromatosis and other forms of iron overload.
AB  - Inherited forms of iron overload are common. HLA-linked hemochromatosis and
      possibly African iron overload are associated with a significant risk of
      developing hepatocellular carcinoma. Early diagnosis and treatment, before
      substantial iron overloading occurs, reduces morbidity and mortality. HLA-linked
      hemochromatosis is easily diagnosed, and routine screening in European-derived
      populations may be appropriate.

PMID- 7712652
TI  - Immunodeficiency syndromes. X-linked agammaglobulinemia, common variable
      immunodeficiency, Chediak-Higashi syndrome, Wiskott-Aldrich syndrome, and X
      linked lymphoproliferative disorder.
AB  - The incidence and mortality of neoplasia in patients with primary
      immunodeficiencies exceed the anticipated rates in the normal population by
      approximately 100 to 300 times. Lymphoreticular malignancies account for the
      majority of tumors, although solid tumors, especially gastric carcinoma, occur
      with increased frequency as well. More than half of these neoplasms are diagnosed
      by ten years of age, except in patients with a later age of onset of
      immunodeficiency. Five primary immunodeficiency disorders with an increased risk
      of neoplasia are reviewed.

PMID- 7712653
TI  - Bloom's syndrome.
AB  - Bloom's syndrome is a rare autosomal recessively transmitted disorder, the main
      clinical feature of which is small body size. A sun-sensitive, erythematous
      facial skin lesion, an excess of well-demarcated hyper- and hypopigmented skin
      lesions located anywhere on the body, and increased numbers of bacterial
      infections due to immunodeficiency are accompanying features of diagnostic value.
      In Bloom's syndrome, the complications are formidable: cancer, chronic lung
      disease, and diabetes. Cancers of the types and sites seen in the general
      population arise frequently and unusually early. Bloom's syndrome cells are
      hypermutable, and excessive numbers of somatic mutations are responsible for many
      of the clinical features. The clinical diagnosis is confirmed cytogenetically by
      demonstrating a characteristic chromosome instability.

PMID- 7712654
TI  - Malignancy in Maffucci's syndrome.
AB  - Maffucci's syndrome is characterized by multiple enchondromas and subcutaneous
      hemangiomas. These tumors typically present in early childhood and may lead to
      significant skeletal deformities. Malignant transformations are a common feature
      of this syndrome and have been reported in approximately 30% of reported cases,
      with chondrosarcomas being the most common.

PMID- 7712655
TI  - Muir-Torre syndrome.
AB  - The Muir-Torre syndrome is an autosomal dominantly inherited genodermatosis with
      malignant potential that is characterized by the presence of at least one
      sebaceous gland tumor (adenoma, epithelioma, or carcinoma) and a minimum of one
      internal malignancy. The syndrome has been documented in 147 individuals.
      Associated features in some of the Muir-Torre syndrome patients are colorectal
      carcinomas and genitourinary neoplasms. More than half of the 292 visceral
      cancers described in Muir-Torre syndrome patients were colorectal carcinomas;
      nearly 60% of these tumors were located at or proximal to the splenic flexure.
      The presence of even a single Muir-Torre syndrome-associated sebaceous tumor
      warrants serious consideration for further evaluation of that individual for the
      syndrome. Therefore, initial and periodic examination for internal malignancy
      should be performed in individuals with such tumors and patients with the
      syndrome. Also, family members of Muir-Torre syndrome patients should be screened
      for Muir-Torre syndrome-associated cutaneous lesions and visceral cancers.

PMID- 7712656
TI  - Multiple endocrine neoplasia 2 (MEN 2)/MEN 2A (Sipple syndrome).
AB  - Multiple endocrine neoplasia type 2A (MEN 2A, Sipple syndrome) is an autosomal
      dominant phakomatosis and is most likely a paracrinopathy. The cardinal
      manifestations of MEN 2A--medullary thyroid carcinoma, pheochromocytoma, and
      hyperparathyroidism--indicate that the condition is one of the inherited cancer
      syndromes. Cutaneous, lichen amyloidosis-like lesions place MEN 2A among the
      genodermatoses. The gene of MEN 2A, designated as MEN2A, is in the
      pericentromeric region of chromosome 10; this allows for reliable prenatal and
      presymptomatic DNA diagnosis.

PMID- 7712657
TI  - Multiple endocrine neoplasia 2B (MEN 2B)/MEN 3.
AB  - Multiple endocrine neoplasia type 2B/3 is characterized by multiple mucosal
      neuromas, a marfanoid appearance, medullary thyroid carcinoma, pheochromocytoma,
      gastrointestinal ganglioneuromatosis, and thickened corneal nerves. This rare
      syndrome is inherited in an autosomal dominant pattern. Early recognition
      followed by appropriate screening and treatment can be life-saving.

PMID- 7712658
TI  - Pharmacokinetics as an aid to optimising compliance with medications.

PMID- 7712659
TI  - Clinical pharmacokinetics and delivery of bovine superoxide dismutase.
AB  - Experimentally, superoxide dismutase (SOD) protects against cytotoxological and
      histotoxological effects of superoxide anions, which play a fundamental role
      where inflammatory processes are involved. Currently, only bovine copper
      containing SOD (Cu-SOD) is available for clinical application in the treatment of
      patients with various arthritic diseases. The intramuscular route is the
      principal route to administer usual dosages of bovine Cu-SOD 4 to 32mg, 2 or 3
      times weekly. A single dose corresponds to an optimal dose ranging from 30 to 200
      micrograms/kg, determined from an established dose-response curve. After
      intramuscular injection of bovine Cu-SOD 8, 16 and 32mg the peak plasma
      concentration occurs 4 to 8 hours postdose and is 0.05, 0.16 and 0.39 mg/L,
      respectively. Clinically this metallo-protein is particularly effective for the
      treatment of inflammation and toxicity resulting from ionising irradiations,
      ischaemia and tumours. The major advantages of liposomally encapsulated bovine Cu
      SOD are its improved pharmacokinetic characteristics, leading to a longer plasma
      half-life and a slower release of free bovine Cu-SOD. In humans, bovine Cu-SOD
      (free or liposomal), although a foreign protein, is well tolerated and produces
      no acute or delayed toxic effects.

PMID- 7712660
TI  - Active hydroxymetabolites of antidepressants. Emphasis on E-10-hydroxy
      nortriptyline.
AB  - Hydroxymetabolites of the antidepressants nortriptyline and desipramine, like the
      parent drugs, inhibit neuronal uptake of noradrenaline (norepinephrine). In both
      plasma and cerebrospinal fluid (CSF), the concentrations of the 10
      hydroxymetabolites of nortriptyline (10-OH-NT) are usually higher than those of
      the parent drugs, but there is a pronounced interindividual variation in the
      plasma concentrations. This shows that during treatment with nortriptyline,
      hydroxymetabolites exert, at least in some patients, major effects on brain
      noradrenaline neurons. Hydroxymetabolites of antidepressants are formed by the
      polymorphic cytochrome P450 enzyme CYP2D6. Nortriptyline is hydroxylated by this
      enzyme in a highly stereospecific way to the (-)-enantiomer of E-10-OH-NT. Among
      Caucasians, 7% are poor metabolisers of the CYP2D6 probe drug debrisoquine. These
      patients will form very little hydroxymetabolite. The affinity of E-10-OH-NT for
      muscarinic acetylcholine receptors in vitro was only one-eighteenth of the
      affinity of nortriptyline for these receptors. In healthy individuals,
      nortriptyline decreased saliva flow to a significantly greater extent than either
      E-10-OH-NT or placebo. In an ultrarapid hydroxylator of nortriptyline treated
      with very high doses of nortriptyline, the plasma concentration of unconjugated
      10-OH-NT was very high without any sign of anticholinergic adverse effects. These
      results show that hydroxymetabolites of nortriptyline have much less
      anticholinergic effect than the parent drug. When racemic E-10-OH-NT per se was
      given to healthy individuals, the plasma concentration of the (-)-enantiomer was
      5-fold higher than that of (+)-E-10-OH-NT. The 2 enantiomers were eliminated in
      parallel with an elimination half-life of 8 to 10 hours. A combined in vitro and
      in vivo investigation showed that a mean of 64% of (+)-E-10-OH-NT was
      glucuronidated in the liver and subsequently eliminated in urine. Of the
      administered (-)-enantiomer, a mean of 36% was eliminated as glucuronide formed
      in the intestine and 35% was actively secreted as unchanged form in urine. Plasma
      protein binding, determined by ultrafiltration, of the (+)- and (-)-enantiomers
      of E-10-OH-NT was 54 and 69%, respectively, which is less than that of
      nortriptyline (92%). The concentration of E-10-OH-NT in CSF was 50% of the
      concentration of unbound in plasma. There seems to be a stereoselective active
      transport of E-10-OH-NT from the CSF to blood. We administered racemic E-10-OH-NT
      to 5 patients during a major depressive episode.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7712664
TI  - Application of microdialysis to clinical pharmacokinetics in humans.
AB  - OBJECTIVE: Measurement of drug concentrations in tissues would be useful for
      clinical pharmacokinetic studies, but appropriate experimental methods are not
      available at present. The aim of this study was to assess the scope and
      limitations of the microdialysis technique for human tissue pharmacokinetic
      studies. METHODS: Microdialysis probes were inserted into the medial vastus
      muscle or the periumbilical subcutaneous adipose layer of 13 healthy volunteers.
      Thereafter, volunteers received either acetaminophen (paracetamol, 1000 mg
      orally) or gentamicin (160 mg, intravenous bolus). Drug concentrations were
      monitored in plasma, muscle, and subcutaneous tissue. Calibration of the
      microdialysis probes was carried out in vitro and in vivo with use of the
      retrodialysis method. RESULTS: For both model compounds, complete concentration
      versus time profiles in muscle and subcutaneous tissue could be obtained. Major
      pharmacokinetic parameters (absorption half-life, elimination half-life, maximum
      concentration, time to reach maximum concentration, area under the curve, and
      area under the inhibitory curve) were calculated for tissues; tissue/plasma
      concentration ratios could be derived. Reproducibility of tissue drug
      concentration measurements was high. CONCLUSIONS: We have shown that
      microdialysis sampling is a suitable tool for measuring drug concentrations in
      human muscle and subcutaneous tissues. Microdialysis is readily applicable,
      relatively noninvasive, and reproducible. This technique may become a valuable
      addition for pharmacokinetic characterization of selected drugs.

PMID- 7712663
TI  - Pharmacokinetics of antisense oligonucleotides.
AB  - Antisense oligonucleotides are promising therapeutic agents for the treatment of
      life-threatening diseases. Intravenous injection of phosphodiester
      oligonucleotide analogue (P-oligonucleotide) in monkeys shows that the
      oligonucleotide is degraded rapidly in the plasma with a half-life of about 5
      minutes. Administration of a single dose of the phosphorothioate (S
      oligonucleotide) in animals by the intravenous route reveals biphasic plasma
      elimination. An initial short half-life (0.53 to 0.83 hours) represents
      distribution out of the plasma compartment and a second long half-life (35 to 50
      hours) represents elimination from the body. This elimination half-life was
      similar when the oligonucleotide was administered subcutaneously. In contrast,
      methylphosphonate oligonucleotides have an elimination half-life of 17 minutes in
      mice. S-Oligonucleotide was distributed into most of organs of rats and mice.
      Liver and kidney were the 2 organs with highest uptake of the oligonucleotide.
      The S-oligonucleotide was primarily excreted in urine. Up to 30% was excreted in
      the first 24 hours. Repeated daily intravenous injections of a 25-mer S
      oligonucleotide into rats showed that the concentrations in the plasma are at
      steady-state during the 8 days' administration. The data represented here support
      the potential utility of phosphorothioate and methylphosphonate oligonucleotides
      as therapeutic agents in vivo.

PMID- 7712666
TI  - Pharmacokinetic analysis of the time course of effect of atracurium.
AB  - OBJECTIVE: To examine the ability to determine clinically important
      pharmacokinetic and pharmacodynamic parameters of atracurium by the analysis of
      the time course of effect without the use of plasma concentration data. DESIGN:
      Neuromuscular transmission was monitored with train-of-four stimulation and
      electromyographic quantitation of the first (T1) and fourth (T4) responses in
      eight anesthetized patients undergoing elective surgery. The time course of onset
      and recovery of neuromuscular blockade by three successive bolus doses of
      atracurium was recorded. Equations describing the theoretic time course of
      concentrations in the effect compartment and the dose-response relationship were
      fitted simultaneously to these data; the parameters of these equations derived
      from the fit of two doses were used to predict the response to a third dose.
      Fitting the equations to all three doses was also performed to assess the
      accuracy of predictions for atracurium. RESULTS: From the depression of the first
      twitch after three consecutive doses in eight patients, the half-lives of uptake
      into and elimination from the effect compartment were 2.1 +/- 0.2 minutes (mean
      +/- SEM) and 25.8 +/- 2.3 minutes (n = 8). The doses producing 50% and 95%
      depression of the first twitch (ED50 and ED95) were 168 +/- 15 and 280 +/- 25
      micrograms/kg, respectively, with a Hill coefficient of 6.1 +/- 0.5. The half
      life of elimination estimated from the fourth twitch was similar to that from the
      first twitch. CONCLUSIONS: The analysis of high-resolution effect data is capable
      of giving pharmacokinetic and pharmacodynamic parameters with clinically
      acceptable accuracy within a short sampling time, without resorting to laboratory
      analysis. This method is specific for active drug and would be of value for
      individualization of administration for short-term treatment.

PMID- 7712665
TI  - Effects of changing liver blood flow by exercise and food on kinetics and
      dynamics of saruplase.
AB  - OBJECTIVE: To investigate the influence of changes in liver blood flow on the
      pharmacokinetics and pharmacodynamics of single-chain unglycosylated urokinase
      type plasminogen activator. METHODS: This open, randomized, crossover trial was
      carried out in the clinical research unit. Infusions of 37.5 mg saruplase and 90
      mg indocyanine green were administered over 150 minutes to 10 healthy male
      volunteers. After 60 minutes the subjects consumed a standardized meal to
      increase liver blood flow or performed an exercise test (20 minutes) to decrease
      liver blood flow. Indocyanine green concentrations, total urokinase-type
      plasminogen activator (u-PA) antigen, two-chain u-PA activity, fibrinogen, total
      degradation products, alpha 2-antiplasmin, and factor XII-dependent fibrinolytic
      activity were measured. Blood flow was measured after food intake in a portal
      vein branch with Doppler echography. RESULTS: The weighted average indocyanine
      green concentration after exercise was increased by 29% compared with baseline
      (steady-state concentration) values (95% confidence intervals [CI]: +6%, +56%).
      After food, the concentration was 27% lower compared with baseline values (95%
      CI: -35%, -19%), and portal vein flow was increased by a maximum of 103% (95% CI:
      +71%, +136%). Average maximal concentrations of u-PA antigen after exercise were
      increased by 130 ng/ml compared with baseline concentrations (95% CI: +65, +195
      ng/ml) and, unexpectedly, 156 ng/ml higher after food (95% CI: +59, +253 ng/ml).
      Although not significant, an increase in average u-PA antigen concentration
      compared with baseline values was detected after both exercise (7%) and food
      (13%). This tendency toward a larger effect after food compared with the effect
      after exercise was reflected by minor changes in the pharmacodynamics.
      CONCLUSIONS: u-PA plasma concentrations were increased by reduced liver blood
      flow induced by exercise. Food intake produced an unexpected increase in u-PA
      concentrations despite increases in liver blood flow.

PMID- 7712667
TI  - Terfenadine pharmacokinetics in breast milk in lactating women.
AB  - The excretion of terfenadine into breast milk has not been reported previously.
      Disposition of terfenadine was prospectively studied in four healthy lactating
      mothers (age, 33 +/- 4 years). Subjects received 60 mg terfenadine every 12 hours
      over a period of 48 hours to achieve steady-state milk and plasma concentrations.
      Milk and plasma samples were collected at 1/2, 1, 1 1/2, 2, 3, 4, 6, 8, 12, 24,
      and 30 hours after the last dose. Terfenadine and its active metabolite milk and
      plasma concentrations were quantitated by HPLC. Terfenadine was not detected in
      milk or plasma. Mean +/- SD active metabolite data for milk and plasma are as
      follows: Cmax (ng/ml), 41.0 +/- 16.4 for milk, 309.0 +/- 120.5 for plasma; tmax
      (hours), 4.3 +/- 2.4 for milk, 3.9 +/- 3.0 for plasma; t1/2 beta (hours), 14.2 +/
      5.4 for milk, 11.7 +/- 6.4 for plasma; AUC(0-12) (ng.hr/ml) 320.4 +/- 99.8 for
      milk, 1590.0 +/- 300.4 for plasma. Metabolite milk/plasmaAUC(0-12) ratios ranged
      from 0.12 to 0.28 (mean, 0.21 +/- 0.07). Newborn dosage estimates based on the
      highest measured concentration of terfenadine metabolite in milk suggests the
      maximum level of newborn exposure would not exceed 0.45% of the recommended
      maternal weight-corrected dose. Estimated amounts consumed by the neonate after
      the mother is given the recommended dose of the drug are not likely to result in
      plasma levels producing untoward effects.

PMID- 7712661
TI  - Pharmacokinetic considerations in gastrointestinal motor disorders.
AB  - Although it has been recognised that alterations in gastrointestinal motility,
      whether induced by physiological or pathological processes, have significant
      effects on the pharmacokinetics of orally administered drugs, this subject has
      received inappropriately little attention. Studies relating to this topic have
      focused on healthy volunteers and animals and have largely been confined to the
      effects of single drug doses. There is limited information about the effects of
      disease on pharmacokinetics under steady-state conditions. Changes in
      gastrointestinal motility may affect the pharmacokinetics of orally administered
      drugs by altering the rate of delivery, bioavailability or mucosal absorption of
      the drug. In general the rate of absorption and time taken to achieve maximal
      plasma concentrations for well absorbed drugs may be modified by changes in
      gastrointestinal motility, but overall bioavailability is not usually affected.
      In these cases the therapeutic and clinical effects of the alteration in
      pharmacokinetics will, therefore, depend on which parameters are important for
      the action of the drug. For poorly absorbed drugs both the rate of absorption and
      bioavailability are likely to be altered by changes in gastrointestinal motility.
      However, the complex effects of food and disease, as well as the properties and
      formulation of any drug (solubility, ease of dispersion, delayed release
      formulation) often make the prediction of the magnitude, or even the direction,
      of any effect difficult to predict. Drugs with direct effects on gastrointestinal
      motility may influence their own patterns of absorption. In patients with
      gastrointestinal motility disorders, drugs administered in a controlled release
      formulation, or those with poor bioavailability, are most likely to have a poorly
      predictable therapeutic effect. Care should be taken to ensure that the
      formulation of the drug, its timing of administration in relation to meals and
      the use of coadministered drugs optimise, or at least ensure consistent
      absorption.

PMID- 7712669
TI  - Theophylline metabolism in healthy nonsmokers and in patients with insulin
      dependent diabetes mellitus.
AB  - This study examined the pharmacokinetics of theophylline and formation of its
      metabolites in patients with insulin-dependent diabetes mellitus (IDDM) and in
      sex-, age-, and weight-matched healthy nonsmokers (n = 8 per group). Subjects
      received a single dose of 5 mg/kg theophylline intravenously. The pharmacokinetic
      parameter values of theophylline (plasma clearance, elimination half-life, and
      volume of distribution) and the formation clearance of theophylline metabolites
      (3-methylxanthine, 1-methyluric acid, and 1,3-dimethyluric acid) were similar
      between the two groups. Plasma free fraction of theophylline was higher in the
      subjects with diabetes than in the healthy subjects (0.61 +/- 0.04 versus 0.56 +/
      0.02; p < 0.001). In the group of subjects with diabetes, there was a positive
      correlation between hemoglobin A1c values and plasma theophylline clearance (r =
      0.76; p < 0.05), formation clearance of 1,3-dimethyluric acid (r = 0.78; p <
      0.05), and formation clearance of 1-methyluric acid (r = 0.71; p < 0.05). These
      results suggest that patients with IDDM and poor glycemic control are more likely
      to have an increased rate of theophylline metabolism.

PMID- 7712668
TI  - Foscarnet and ganciclovir pharmacokinetics during concomitant or alternating
      maintenance therapy for AIDS-related cytomegalovirus retinitis.
AB  - INTRODUCTION: The use of foscarnet and ganciclovir as a combination treatment for
      cytomegalovirus retinitis is increasing because of limitations associated with
      single agent therapy. METHODS: The pharmacokinetics of foscarnet and ganciclovir
      were determined in 13 patients receiving either concomitant therapy (regimen A)
      or daily alternating therapy (regimen B) for maintenance of cytomegalovirus
      disease. For regimen A, 60 mg/kg intravenous foscarnet and 3.75 mg/kg ganciclovir
      were sequentially administered daily; for regimen B, 120 mg/kg foscarnet and 6
      mg/kg ganciclovir were administered on alternating days. For both regimens,
      serial blood sampling for pharmacokinetic analysis was performed for each drug
      alone (day 1 or 2) and after 2 weeks of combination therapy. Plasma samples for
      foscarnet and ganciclovir analysis were performed by means of high-performance
      liquid chromatography. Pharmacokinetic analysis was performed with
      noncompartmental methods. RESULTS: For regimen A, the plasma clearance (CL) of
      foscarnet did not change in the presence of ganciclovir, averaging 0.12 +/- 0.08
      and 0.11 +/- 0.02 L/hr/kg on study days 2 and 14, respectively (p = 0.34). The
      volume of distribution (VSS) and mean residence time (MRT) also did not change
      significantly. CL and MRT of foscarnet did not change for regimen B, although a
      slight increase in VSS was observed before (0.38 +/- 0.05 L/kg) and after (0.46
      +/- 0.07 L/kg) alternating therapy (p = 0.03). Ganciclovir CL did not change for
      either regimen, with mean values of 0.21 +/- 0.10 and 0.25 +/- 0.10 L/hr/kg
      (regimen A, p = 0.17) and 0.32 +/- 0.10 and 0.34 +/- 0.11 L/hr/kg (regimen B, p =
      0.24). MRT and VSS were also not significantly different. CONCLUSION: These
      plasma data suggest that further dosage adjustments are unnecessary for or
      alternating maintenance therapy.

PMID- 7712670
TI  - Stereoselective pharmacokinetics of oxprenolol and its glucuronides in humans.
AB  - OBJECTIVE: To study the pharmacokinetics of R(+)- and S(-)-oxprenolol and their
      corresponding glucuronide conjugates in healthy subjects. METHODS: An oral dose
      of 80 mg racemic oxprenolol was given to eight male volunteers. Venous blood
      samples and urine were collected as a function of time. Oxprenolol enantiomers in
      plasma and urine were determined by an enantiospecific HPLC method. Oxyprenolol
      glucuronides in plasma and urine were measured as oxprenolol equivalents after
      enzymatic hydrolysis. RESULTS: For R-oxprenolol the area under the plasma
      concentration-time curve was slightly higher (R/S ratio, 1.19) and the oral
      clearance slightly lower (R/S ratio, 0.84) than those parameters for S
      oxprenolol. The free fraction of R-oxprenolol in plasma was 4% higher than that
      of S-oxprenolol. The intrinsic clearance of S-oxprenolol was 1.5 times larger
      than that of R-oxprenolol, and a maximum of 3% of the dose was excreted as
      unchanged enantiomers in the urine. The plasma concentrations of S-oxprenolol
      glucuronide were more than three times higher than those of R-oxprenolol
      glucuronide. Twenty-five percent of the dose of the R-enantiomer was excreted in
      the urine as R-oxprenolol glucuronide; 29% of the S-enantiomer dose was excreted
      as S-oxprenolol glucuronide. The renal clearance of R-oxprenolol glucuronide was,
      on average, 172 ml/min, suggesting active tubular secretion. In contrast, the
      renal clearance of S-oxprenolol glucuronide was only 49 ml/min, which can be
      explained by the plasma binding of the compound. CONCLUSIONS: Our results show
      small differences in disposition between R- and S-oxprenolol but a marked
      difference in disposition between the glucuronides. The difference in plasma
      concentrations between the oxprenolol glucuronides is mainly attributable to the
      stereoselectivity of the renal excretion.

PMID- 7712662
TI  - Pharmacokinetic optimisation of the treatment of embolic disorders.
AB  - Management of thromboembolic disease involves administration of anticoagulants,
      thrombolytics or antiplatelet agents to lyse or prevent thrombus extension.
      Despite widespread use and decades of experience with some of these agents, much
      is unknown about the effects of dose and plasma concentration on patient
      response. Unfractionated heparin (UFH) improves outcome in many thromboembolic
      disorders when administered to a target activated partial thromboplastin time
      (aPTT) or plasma heparin concentration. UFH exhibits dose-dependency both with
      absorption from subcutaneous sites and elimination. Doses based on bodyweight or
      estimated blood volume attain therapeutic aPTTs faster than fixed or standard
      doses. Low molecular weight heparins (LMWHs) were developed to increase the anti
      factor Xa:anti-factor IIa activities. Several different LMWHs are as effective as
      UFH in treating deep venous thrombosis. Evidence fails to support a relationship
      between anti-factor Xa activity and either thrombosis evolution or bleeding. No
      comparisons have been made between bodyweight-based and anti-factor Xa activity
      based doses. The dose of orally administered warfarin is adjusted to achieve a
      target International Normalised Ratio (INR). Maintenance doses are estimated on
      the basis of the patient's INR during the first 3 days of therapy: the dose
      required to achieve an optimal INR decreases with age > 50 years. The
      thrombolytic agents are administered in standard doses to achieve rapid
      thrombolysis with minimal alteration in systemic haemostasis. Accelerated
      intravenous alteplase may result in the highest rate of coronary artery
      reperfusion. Nevertheless, standard doses of streptokinase, anisoylated
      plasminogen streptokinase complex and alteplase result in similar 1-month
      mortality rates. The minimal advantage seen with alteplase is offset by higher
      rates of stroke. Future trials will focus on administration strategies achieving
      rapid thrombolysis, while minimising the risk of serious bleeding. With the
      antiplatelet agents, unpredictability in the pharmacokinetic parameters of
      different products has confounded interpretation of published reports. Optimal
      aspirin (acetylsalicylic acid) administration would include administration of an
      initial dose of 160 to 325mg after an acute vascular event, followed by
      maintenance dosages of approximately 75 mg/day for prophylaxis or treatment.
      Ticlopidine does not exhibit a relationship between either plasma concentration
      or dose and adverse effects, while pharmacodynamic effects may be dose-, but not
      plasma concentration-, dependent. The correlation between the concentration of
      dipyridamole and some of its antiplatelet effects may be the strongest amongst
      all the antiplatelet agents. However, unfortunately all clinical trials used
      standard doses and the current consensus is that dipyridamole alone is not an
      effective antiplatelet agent.

PMID- 7712671
TI  - Effect of dietary fat on the pharmacokinetics and pharmacodynamics of
      cyclosporine in kidney transplant recipients.
AB  - OBJECTIVE: To investigate the effect of dietary fat on the pharmacokinetics and
      pharmacodynamics of cyclosporine. METHODS: Sixteen stable kidney transplants
      recipients (mean age, 50.4 years; age range, 19 to 63 years; six women) who were
      maintained on oral cyclosporine therapy were randomized to receive a high- or low
      fat diet for periods of 7 days in a balanced crossover study. The crossover was
      separated by a 7-day washout period, when the usual diet was followed. Oral
      cyclosporine was taken once daily with breakfast. Twenty-four-hour
      pharmacokinetic studies were conducted during each dietary period on day 6 after
      oral cyclosporine and on day 7 after a 3-hour intravenous cyclosporine infusion
      (30% of oral dose). Sequential blood samples were also taken after the oral dose
      on day 6 for lymphocyte transformation studies. RESULTS: The mean breakfast fat
      intake and total daily fat intake were 6.5 and 5.5 times higher, respectively,
      during the high-fat diet than during the low-fat diet. The bioavailability and
      clearance of cyclosporine were found to be significantly higher during the high
      fat diet (p = 0.02 and p = 0.01, respectively). As a consequence, the area under
      the blood concentration-time curve (AUC) after the oral dose was not
      significantly different between the two diets. There were no significant
      differences in concanavalin A-stimulated proliferation of peripheral blood
      lymphocytes between the high- and low-fat diets. CONCLUSIONS: An increased fat
      content of food significantly increases cyclosporine bioavailability and
      clearance. However, this is unlikely to be of clinical importance during oral
      administration because the AUC and pharmacodynamics of cyclosporine are not
      affected significantly.

PMID- 7712672
TI  - Microsomal enzyme inducers raise plasma high-density lipoprotein cholesterol
      levels in healthy control subjects but not in patients with primary
      hypoalphalipoproteinemia.
AB  - In this study we compared the ability of phenytoin, a microsomal enzyme inducer,
      to raise plasma high-density lipoprotein (HDL) levels in normolipidemic subjects
      and patients with primary hypoalphalipoproteinemia. In healthy control subjects,
      phenytoin caused a dose-dependent increase of plasma HDL, HDL2, and HDL3
      cholesterol levels, up to 40% to 50%. Minor changes were recorded in the plasma
      concentrations of apolipoprotein (apo) A-I and apo A-II; the plasma level of the
      cholesteryl ester transfer protein (CETP) decreased by 42%. In contrast, none of
      the patients with hypoalphalipoproteinemia had changes in plasma HDL, HDL2, or
      HDL3 cholesterol, apo A-I, apo A-II, or CETP levels. These findings indicate that
      microsomal enzyme inducers are unsuitable to increase plasma HDL levels in high
      risk patients with primary hypoalphalipoproteinemia, and they disclose a new
      mechanism, that is, decreased CETP-mediated transfer of cholesterol out of HDL,
      for the HDL-raising effect of microsomal enzyme inducers in healthy individuals.

PMID- 7712673
TI  - Topical benzoic acid induces the increased biosynthesis of prostaglandin D2 in
      human skin in vivo.
AB  - BACKGROUND: Benzoic acid is one of the most commonly used preservatives in
      cosmetics, foodstuffs, and drug preparations. Nonetheless, products containing
      this compound frequently induce cutaneous erythema. Previous studies have
      suggested that prostaglandins may mediate the cutaneous vasodilation because
      ingestion of cyclooxygenase inhibitors before the application of benzoic acid
      markedly diminishes this symptom. However, the prostaglandin responsible has not
      been conclusively determined. Recently we showed that cutaneous erythema similar
      to that associated with application of venzoic acid is induced by the topical
      administration of another preservative, sorbic acid, and is mediated by the
      increased biosynthesis of prostaglandin (PG)D2 in the skin. This study was
      designed to determine whether the cutaneous vasodilation induced by benzoic acid
      is mediated by this prostaglandin in humans. DESIGN: Benzoic acid (10% in
      petrolatum) was applied to the forearms of healthy volunteers. Blood was obtained
      from the antecubital vein draining the treated site and assayed for vasodilating
      prostaglandins and histamine. RESULTS: Topical application of benzoic acid to
      four volunteers resulted in a 29- to 8000-fold increase in plasma levels of PGD2
      and a 72- to 370-fold increase in levels of 9 alpha,11 beta-PGF2, the stable
      plasma metabolite of PGD2, in blood drawn from the antecubital vein draining the
      treated sites. In contrast, there were no changes in plasma levels of other
      vasodilating prostaglandins, PGE2 or prostacyclin (PGI2). Increases in levels of
      PGD2 and 9 alpha,11 beta-PGF2 were not found in blood drawn simultaneously from
      veins in the contralateral arm, indicating the increased biosynthesis of PGD2
      from the site of benzoic acid application. Increased formation of PGD2 in
      response to topical application of benzoic acid was dose dependent over a
      concentration range of 0.01% to 15%. The increased synthesis of PGD2 was not
      accompanied by a release of histamine, suggesting that PGD2 was not derived from
      the mast cell. CONCLUSIONS: PGD2 mediates the vasodilation associated with
      topical application of benzoic acid.

PMID- 7712674
TI  - Pharmacokinetics and pharmacodynamics of neutrophil-associated ciprofloxacin in
      humans.
AB  - OBJECTIVE: To study the possibility that the penetration of the antibiotic
      ciprofloxacin into polymorphonuclear leukocytes (PMN) may be associated with some
      changes in cell reactivity. DESIGN: Superoxide anion and chemiluminescence
      generation induced by formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet
      activating factor (PAF) were studied ex vivo in 12 healthy volunteers (mean age,
      53.15 +/- 16.3 years; mean body weight, 71.23 +/- 6.9 kg) at fixed intervals up
      to 72 hours from the administration of a single oral dose of 250 mg
      ciprofloxacin. Cytosolic free calcium levels ([Ca2+]i) in resting and stimulated
      cells were also evaluated. The dynamic parameters of the effects on PMNs were
      compared with the kinetic profile of the drug in plasma and in PMNs. RESULTS:
      Superoxide generation induced by the stimulating agents increased significantly,
      reaching a peak after 12 hours (+116% [p < 0.001] for fMLP and +66% [p < 0.05]
      for PAF). Similarly, chemiluminescence production showed a threefold increase in
      the response to the stimulating agents 12 hours after drug administration (p <
      0.001). The increase in [Ca2+]i in stimulated PMNs was significantly potentiated
      (p < 0.001). The mathematic analysis of the effects of ciprofloxacin showed that
      time to maximal activity was between 10.4 hours (PAF-dependent [Ca2+]i increase),
      and 15 hours (fMLP-induced superoxide anion and chemiluminescence production).
      The ratio of PMNs to plasma ciprofloxacin concentration increased progressively,
      from 0.5 at 30 minutes to 10.4 after 24 hours. In addition, time to maximal
      activity and half-life differed in PMNs and in plasma (4.66 versus 1.90 hours and
      13.03 versus 7.28 hours, respectively). CONCLUSIONS: Ciprofloxacin administration
      induced a long-lasting enhancement of PMN reactivity to fMLP and PAF. The levels
      of the drug in the cells were greater and more sustained in the time than those
      in plasma.

PMID- 7712675
TI  - A bioassay for topical and systemic effect of three inhaled corticosteroids.
AB  - BACKGROUND: Comparisons of relative potency for the three inhaled corticosteroids
      in the United States are limited to assessment of skin blanching. OBJECTIVE:
      Development of a method for comparing relative potencies of inhaled
      corticosteroids for topical effect on human airway and systemic effect. METHODS:
      With use of partial suppression of immediate response to inhaled allergen and 24
      hour urinary free cortisol output, three-point dose-response curves were
      constructed for beclomethasone dipropionate (50 micrograms/puff), triamcinolone
      acetonide (100 micrograms/puff), and flunisolide (250 micrograms/puff). A
      randomized, parallel, single-blind study design was used. Dosing began with one
      puff four times a day for flunisolide and two puffs four times a day for the
      others. Doses were doubled after 1 week and again after a second week. RESULTS:
      Twenty-five patients completed the study. Dose-response relationships were shown
      for each inhaled corticosteroid for both topical and systemic effect. Dose
      response curves for the three preparations were similar when response was plotted
      against delivered dose in micrograms. CONCLUSION: Within the limits of the
      assays, relative potencies of the three preparations appeared to be approximately
      equivalent for both topical and systemic effect when dose was expressed in
      micrograms. Relative potency per puff is therefore approximately proportional to
      the dose delivered. This method has potential for evaluation of relative potency
      of newer inhaled corticosteroids and the relative advantage of alternative
      delivery systems.

PMID- 7712676
TI  - Orocecal transit time in humans assessed by sulfapyridine appearance in saliva
      after sulfasalazine intake.
AB  - PURPOSE: We propose a noninvasive method for the measurement of orocecal transit
      time assessed by the sulfapyridine appearance time in saliva after ingestion of
      sulfasalazine. METHOD: In 12 healthy volunteers, we studied the correlation
      between plasma and saliva sulfapyridine appearance times and then the
      sulfapyridine appearance times in saliva under various experimental conditions to
      assess the reproducibility, the effects of meals, and the role of the
      formulation, and the effects of gastrointestinal kinetic drugs. RESULTS: The
      correlation between saliva and plasma sulfapyridine appearance times was strong
      (r = 0.84; p = 0.0004). The sulfapyridine saliva appearance time was
      significantly delayed by the meal. Compared with placebo, the saliva
      sulfapyridine appearance time was reduced by cisapride (312 +/- 128 versus 551 +/
      97 minutes; p = 0.0001) and increased by loperamide (674 +/- 267 versus 501 +/-
      131 minutes; p = 0.044). CONCLUSION: We propose the salivary sample method as a
      validated simplification of the plasma sulfasalazine-sulfapyridine test for the
      measurement of orocecal transit time.

PMID- 7712677
TI  - Lidocaine prophylaxis for fatal ventricular arrhythmias after acute myocardial
      infarction.
AB  - OBJECTIVE: To compare the efficacy and safety of a 40-hour lidocaine infusion
      after completion of a 8-hour open-label infusion for prophylaxis of primary
      ventricular fibrillation in patients with uncomplicated acute myocardial
      infarction. METHODS: This was a double-blind, randomized placebo-controlled trial
      held in the coronary care unit of a large nonprofit hospital. We studied 200
      patients with uncomplicated acute myocardial infarction in Killip class I or II
      who came to the hospital within 6 hours of onset of symptoms and 22 patients who
      had ventricular fibrillation before the start of the study. Intervention
      consisted of an 8-hour lidocaine infusion followed by placebo or lidocaine for an
      additional 40 hours. The infusion rate was adjusted in patients > or = 70 years
      old and in those < 50 kg or > or = 90 kg. Measurements recorded were baseline
      demographic characteristics, incidence of ventricular arrhythmias, adverse
      reactions, and death. RESULTS: New congestive heart failure developed during the
      randomized phase in 9% of patients receiving lidocaine and in 2% of patients
      receiving placebo (p = 0.03). Ventricular fibrillation did not occur during the
      treatment period, and sustained ventricular tachycardia developed in one patient
      receiving placebo. The in-hospital mortality rate was comparable in both groups
      (4% versus 2%; p = 0.68) but was much higher (13.6%) in patients with initial
      ventricular fibrillation not included in the randomized study. CONCLUSIONS: A 40
      hour age- and weight-adjusted lidocaine infusion administered after an initial 8
      hour infusion provoked more congestive heart failure than placebo. In view of the
      absence of ventricular fibrillation episodes with both infusions, caution should
      be used when lidocaine is administered for longer than 8 hours in patients with
      uncomplicated myocardial infarction.

PMID- 7712678
TI  - Nontobacco sources of cotinine in the urine of nonsmokers.

PMID- 7712679
TI  - Streptozotocin and alloxan are comparable agents in the diabetic model of
      impaired wound healing.
AB  - This study compares the drugs Streptozotocin (STZ) and Alloxan (ALN) in the
      diabetic wound healing model to determine the effect of their diverse immunologic
      and metabolic activity upon wound collagen and collagenase. Levels of
      hydroxyproline (as a measure of collagen) and collagenase were determined in
      polytetrafluorethylene (PTFE) wound cylinders harvested from STZ and ALN-diabetic
      rats and nondiabetic controls on post-operative days 5, 10 and 20. Animals
      treated with STZ and ALN had significantly less hydroxyproline on day 5 compared
      to control rats (p < 0.05). However, no difference was noted on days 10 and 20
      between these two agents and controls, or between STZ and ALN at any time in the
      experiment. Despite their markedly dissimilar side effects, we conclude that
      either drug is appropriate in the diabetic wound healing when determining wound
      collagen and collagenase activity in this setting.

PMID- 7712680
TI  - Iterative pulse administration of succinic acid monomethyl ester to
      streptozotocin diabetic rats.
AB  - In adult rats injected intravenously with streptozotocin (STZ: 20 or 40 mg/kg
      body wt) and examined 13 days later, the secretory response of the perfused
      pancreas to D-glucose is impaired. A paradoxical inhibition of insulin release is
      even observed in the perfused pancreas of rats given the high STZ dose. When
      pulses of succinate monomethyl ester (SAM: 60 mg) were administered
      intraperitoneally three times a day for one week from the 6th to 12th day after
      STZ injection, no obvious difference in insulin output from the perfused pancreas
      stimulated with either D-glucose or SAM was observed between SAM-treated and
      untreated rats first injected with the low STZ dose. However, in rats first
      injected with the high STZ dose, the secretory response to SAM was higher in SAM
      treated than untreated animals. These findings raise the view that suitable non
      glucidic nutrient secretagogues might improve, in a long term manner, the
      secretory potential of the endocrine pancreas in animal models of diabetes
      characterized by a preferential impairment of the B-cell response to D-glucose.

PMID- 7712681
TI  - Diabetes and accompanying obesity, hypertension and ECG abnormalities in Yemenite
      Jews 40 years after immigration to Israel.
AB  - A repeat survey in 1988-1989 on the prevalence of diabetes among Yemenites aged
      30 years and over was 3.6% as compared to 2.9% in 1977-78 and 0.25% in 1958-59
      soon after their immigration to Israel. In age and gender-matched ethnic Jewish
      groups at the time it was 5/9% in Ashkenazis (originating in Europe and North
      America) and 2.5% in Sephardis (originating from Mediterranean and Middle Eastern
      countries). In Yemenites obesity was associated with a marked increase in the
      prevalence of diabetes the same as in the other ethnic groups. The prevalence of
      hypertension and ischemic heart disease ECG changes were higher in diabetic
      Yemenites than in non-diabetic ones, the same as in the other ethnic groups.
      There was no difference between the incidence of ischemic heart disease ECG
      changes among diabetics and subjects with IGT. These facts suggest that the
      metabolic changes that accompany the development of diabetes lead to the same
      pathological changes irrespective of the ethnic group.

PMID- 7712682
TI  - Increased red cell rigidity might affect retinal capillary blood flow velocity
      and oxygen transport efficiency in type II diabetes.
AB  - Retinal capillary blood flow velocity, oxygen transport efficiency (TE) and
      rheological properties of the blood were measured from twenty-two type II
      diabetes patients and nineteen normal subjects. The results showed that diabetic
      patients had increased plasma viscosity (P < 0.01). Also, for both shear rates of
      225 sec-1 and 450 sec-1, they had increased blood viscosity (P < 0.002, both),
      red cell rigidity (Tk) (P < 0.002 and P < 0.001, respectively), but lower values
      of TE (P < 0.001, both), and of retinal capillary blood flow velocity (P <
      0.005). Furthermore, TE was linearly correlated with Tk for both shear rates of
      all subjects (r = -0.80, gamma = 225 sec-1, P < 0.001; r = -0.84, gamma = 450 sec
      1, P < 0.001). The impaired rheological properties of blood and red cell rigidity
      might result in both reduced capillary blood flow velocity and lower values of
      TE, which then possibly contribute to the deterioration of retinopathy or
      microangiopathy in diabetic patients.

PMID- 7712683
TI  - Naloxone effects on post-prandial glucose, insulin and C-peptide levels in obese
      subjects.
AB  - In order to investigate the relationships between glucose metabolism, insulin
      secretion and endogenous opioids in obese patients, we have studied the effects
      of a naloxone infusion on insulin and C-peptide release after a normal meal (800
      kcal) eaten at 12.00 hr in 16 obese women, aged 20-61 yr, with a BMI ranging from
      25 to 37.2 kg/m2, with normal glucose tolerance (Group 1) and with NIDDM (Group
      2). Naloxone was administered in a bolus of 1.6 mg i.v., followed by a continuous
      infusion of 4 mg in 2 hr starting immediately after feeding. In Group 1 naloxone
      infusion significantly increased the glucose levels, but insulin secretion was
      unaffected. In Group 2, naloxone infusion failed to modify significantly the
      postprandial levels of glucose, insulin and C-peptide. Therefore, in our study
      naloxone infusion seems to have beta-endorphin-like effects in non-diabetic obese
      subjects by increasing their glycemic levels, with no evidence of expected
      insulin decrease. In diabetic obese patients we observed a trend towards decrease
      in glycemic values during naloxone infusion, as expected, due to insulin plasma
      levels increase. By these data we can hypothesise a complex regulatory role of
      opioids in metabolic balance in obesity. In diabetic patients, naloxone can
      improve the surviving insulin secretion with better glucose tolerance. In non
      diabetic subjects naloxone exerts its effects, probably, on peripheral organs.

PMID- 7712684
TI  - Humoral-mediated cytotoxicity to rat pancreatic exocrine cells in serum of
      diabetes-prone BB/OK rats--predictive value for diabetes onset.
AB  - Diabetes-prone BB/OK rats were checked in a follow-up study between 40 and 200
      days of age for the appearance of humoral-mediated cytotoxicity to rat pancreatic
      exocrine cells in serum by 51Cr-release assay. BB/OK rats maintaining
      normoglycaemia were characterized by a pronounced decrease of anti-exocrine cell
      cytotoxicity in serum at 75 and 105 days of age compared to the initial value at
      day 40. In contrast, in animals developing diabetes cytotoxicity was found more
      frequently and the level of cytotoxicity did not likewise decrease during the
      period up to diabetes onset. With respect to the prediction of diabetes in
      individual BB/OK rats the retrospective analysis revealed that 81.0% of those
      animals displaying cytotoxicity at 75 days of age subsequently developed
      diabetes. If sera from BB/OK rats were identified as non-cytotoxic at day 75 and
      also at 105 days of age normoglycaemia persisted in 83.3% of these animals. Thus,
      screening of young diabetes-prone BB/OK rats for the presence of humoral-mediated
      cytotoxicity to pancreatic exocrine cells in serum seems to facilitate the
      identification of potential diabetic or long-term normoglycaemic animals in the
      BB/OK rat population.

PMID- 7712685
TI  - Long term use of captopril or nifedipine in normotensive microalbuminuric
      patients with insulin-dependent diabetes mellitus.
AB  - Several studies have suggested that ACE-inhibition may be effective in postponing
      the onset of nephropathy in insulin-dependent diabetic subjects. In contrast,
      other drugs might have opposing effects. To study the long term effects of either
      captopril or nifedipine in normotensive, microalbuminuric patients with insulin
      dependent diabetes mellitus, eighteen subjects received either placebo (n = 5,
      P), 20 mg nifedipine daily (n = 7, N) or 50 mg captopril daily (n = 6, C) for one
      year. Baseline clinical and laboratory variables were comparable in the three
      groups. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and
      blood pressure did not differ between groups before and after one years
      medication. UAER did not change in the captopril and the placebo group (C: -12.6%
      (-58.1 to 51.8%)' P: -17.3 (-55.9 to 99.3%), medians and ranges. In contrast, in
      the patients that received nifedipine, UAER rose by 43.1% (-8.5 to 261.8%), (p <
      0.05 Baseline vs one year, and one year nifedipine vs captopril and placebo). We
      therefore conclude, that long-term use of nifedipine increases UAER in
      normotensive microalbuminuric insulin-dependent subjects, in contrast to
      captopril or placebo. Whether this enhancement of microalbuminuria exerts an
      adverse effect on renal function in the long-term is yet unknown, but caution
      seems warranted.

PMID- 7712687
TI  - Effect of beta-blocker therapy on serum lipoprotein profiles in patients on renal
      dialysis and in diabetic nephropathy.
AB  - We determined whether the serum lipoprotein levels in insulin-dependent diabetic
      patients (IDDM) with nephropathy and in patients on haemodialysis or continuous
      ambulatory peritoneal dialysis were affected by beta-blocker therapy. A case
      control study was performed in 18 IDDM patients with diabetic nephropathy, in 18
      patients receiving chronic haemodialysis (HD) and 16 patients undergoing
      continuous ambulatory peritoneal dialysis (CAPD). In IDDM patients with diabetic
      nephropathy very low density lipoprotein-cholesterol (VLDL-CHOL) (0.680 +/- 0.17
      vs 0.197 +/- 0.04 mmol/l, p = 0.004), total triglycerides (1.71 +/- 0.23 vs 0.808
      +/- 0.14 mmol/l, p = 0.004) and very low density lipoprotein triglyceride (VLD
      TG) were higher in the beta-blocker therapy group. In haemodialysis patients,
      beta-blocker therapy caused no significant changes in the serum lipoprotein
      profiles compared to the control group. In patients receiving continuous
      ambulatory peritoneal dialysis VLDL-CHOL was significantly higher (1.47 +/- 0.24
      vs 1.08 +/- 0.21 mmol/l, p = 0.042) and cholesterol-high density lipoprotein (HDL
      CHOL) was lower in the beta-blocker therapy group. The elevated VLDL-CHOL level
      (0.96 +/- 0.12 vs 1.24 +/- 0.14 mmol/l, p = 0.021) was correlated with the
      duration of CAPD in patients receiving beta-blocker therapy. Antihypertensive
      therapy with beta-blockers in IDDM patients with persistent proteinuria and in
      patients on continuous ambulatory peritoneal dialysis appears to adversely effect
      serum lipoproteins which may add to their cardiovascular risk.

PMID- 7712686
TI  - Pancreatic reserve and insulin dose in type 2 diabetic patients.
AB  - In order to determine whether there is any relationship between pancreatic
      reserve and the insulin dose required for achieving a good metabolic control in
      type 2 diabetic patients with secondary failure to oral hypoglycaemic agents,
      fasting and post-glucagon C-peptide were determined in thirty-nine type 2
      diabetic patients with secondary failure to sulphonylureas and hyperglycaemia <
      250 mg/dl who attended an outpatient clinic. M-value was calculated in patients
      performing self-monitoring of blood glucose. Otherwise, pre- and post-prandial
      glycaemias were measured bi-weekly as outpatients. HbA1c and fructosamine were
      assessed monthly. A patient was considered well controlled when he or she
      fulfilled all the requirements of the European NIDDM Policy Group and the insulin
      dose necessary for these goals was correlated to the pancreatic reserve. There
      were two drop-outs. Thirty-five out of the thirty-seven patients complied with
      the objectives in an average time of 3.14 +/- 1.93 months. At the beginning of
      the study mean HbA1c was 8.01 +/- 1.40% and fructosamine 343.81 +/- 59.05
      micromol/l, whereas at the end of the study the values were 6.91 +/- 0.94% and
      291.89 +/- 38.59 micromol/l, respectively (both p < 0.001). Body weight increased
      from 68.95 +/- 12.40 to 69.44 +/- 12.54 kg (n.s.), while hypoglycaemic events
      decreased from 1.70 +/- 2.37 to 0.88 +/- 1.33 events/week (p < 0.05). To attain
      all the objectives, 19.03 +/- 5.98 i.u. (0.28 +/- 0.08 i.u./kg) of insulin were
      required. Basal and post-glucagon C-peptide were 1.97 +/- 1.24 and 3.29 +/- 1.85
      ng/ml, respectively, with an increase of 1.32 +/- 0.78 ng/ml. All these values
      inversely correlated with insulin dose, especially the increase during the test
      (r = -0.652 with i.u./kg and r = -0.599 with i.u., both p < 0.01). In conclusion,
      C-peptide test is a good indicator of the insulin dose required for achieving the
      aims of metabolic control in type 2 diabetic patients.

PMID- 7712688
TI  - Assessment of glucose metabolism in humans with the simultaneous use of indirect
      calorimetry and tracer techniques.
AB  - Concomitant measurements of sytemic glucose delivery and carbohydrate oxidation
      are frequently performed in human investigations. Systemic glucose delivery (SGD)
      is usually determined using dilution of infused glucose tracers; net carbohydrate
      oxidation rate (net CHOOX) can be calculated from respiratory gas exchanges and
      urinary nitrogen excretion (indirect calorimetry); alternatively, glucose
      oxidation can be measured from labelled CO2 production during infusion of carbon
      labelled glucose tracers. In this paper, the theory underlying the use of each of
      these techniques is briefly reviewed and qualitative differences are outlined.
      SGD represents the sum of hepatic glucogenolysis, gluconeogenesis from amino
      acids or glycerol, and, according to the glucose tracer used, glucose cycles
      (glucose-phosphate cycle, fructose-phosphate cycle, Cori and glucose-alanine
      cycles); systemic delivery of exogenous glucose after oral or i.v. glucose
      administration is also measured. Net CHOOX represents oxidation of glucose
      arising from hepatic or muscle glycogen or from exogenous glucose; it does not
      take into account oxidation of glucose formed from amino acids or glycerol, which
      is included in net protein or lipid oxidation. In contrast, isotopic
      determination of glucose oxidation corresponds to oxidation of glucose
      originating from hepatic glycogen breakdown, of exogenously administered glucose,
      and of glucose formed from amino acids and glycerol. Non-oxidative glucose
      disposal, calculated as SGD-net CHOOX, corresponds to the sum of gluconeogenesis
      from amino acids or glycerol (which are included in net protein and lipid
      oxidation), glucose cycles, and glycogen synthesis.

PMID- 7712690
TI  - Effect of hypoxia on muscle oxygenation and metabolism during arm exercise in
      humans.
AB  - The influence of hypoxaemia on anaerobic energy production during arm exercise
      (AE) has been investigated. Six men were studied during maximal AE and during 10
      min of sitting submaximal AE under both normoxic (AEN) and hypoxic (AEH,
      respiratory hypoxia, 12% O2) conditions. Peak pulmonary oxygen uptake (VO2)
      during maximal AE in normoxia and hypoxia was 2.25 +/- 0.15 and 2.18 +/- 0.14 l
      min-1, respectively (P < 0.05). The absolute workload was the same during
      submaximal AEN and AEH and corresponded to 54% of peak VO2 during normoxic
      maximal AE. To eliminate the potential influence of differences in catecholamine
      levels on the metabolic response, the submaximal experiments were performed
      during beta-adrenoceptor blockade. Oxygen deficit was 1.45 +/- 0.26 and 1.67 +/-
      0.191 during AEN and AEH, respectively (n.s.). Oxygen extraction at steady state
      was lower during AEH than during AEN, and assuming a similar O2 demand this
      corresponds to a 14% higher muscle blood flow during AEH. At the onset of both
      AEN and AEH, O2 extraction (a-v O2) across the arm increased transiently above
      that at steady state, the increase being more pronounced during AEN than during
      AEH (P < 0.05). Muscle oxygenation, measured by near-infrared spectroscopy,
      demonstrated an initial decrease which was partially reversed as exercise
      proceeded. The reversal of muscle O2 desaturation was slower in all subjects
      during AEH (t1/2 = 2.4 +/- 0.2 min) than during AEN (t1/2 = 1.2 +/- 0.2 min; P <
      0.01). After 10 min of exercise, arterial blood lactate was higher (P < 0.05)
      during AEH (5.5 +/- 0.2 mmol l-1) than during AEN (4.9 +/- 0.6 mmol l-1), whereas
      arterial plasma ammonia (NH3) was similar. The arteriovenous difference for both
      lactate and ammonia was similar during AEN and AEH. It is concluded that the high
      anaerobic energy production at the onset of AE is associated with a transient
      increase in O2 extraction and a transient decrease in muscle oxygenation. The
      effects of hypoxaemia on peak VO2, oxygen deficit and blood metabolites are less
      pronounced than previously described during submaximal leg exercise (LE).

PMID- 7712689
TI  - Effect of 6 months of exercise training on cardiovascular responses to head-up
      tilt in the elderly.
AB  - The purpose of this investigation was to evaluate the effect of 6 months of
      exercise training on cardiovascular responses to 70 degrees head-up tilt (HUT) in
      the elderly. Forty-four elderly men and women (ages 60-82 years) were assigned to
      endurance training alone (n = 18), endurance training in combination with
      selected resistance exercises (n = 17), or to a non-exercising control group (n =
      9). Head-up tilt testing at the start (T1) and end (T2) of 26 weeks of training
      consisted of 30 min of supine rest, 15 min of 70 degrees HUT, and 15 min of
      supine recovery. Endurance training consisted of uphill treadmill walking or
      stair climbing exercise 3 times per week, 30-45 min/day, at 75-85% of maximal
      heart rate reserve. In addition, the endurance/resistance group completed one set
      of 8-15 repetitions of biceps curl (BC), triceps extension (TE), and leg press, 3
      times per week. After 26 weeks, increases in VO2max averaged 16.2% and 12.3% for
      endurance and endurance/resistance groups, respectively. In addition, the
      endurance/resistance group increased BC and TE strength by 25.3% and 26.1%,
      respectively. Results from the HUT test indicated that only the endurance group
      increased supine resting stroke volume (SV) and cardiac output (Q) from T1 to T2;
      however, SV and Q during HUT were not augmented as a result of training. Training
      did not affect heart rate, blood pressure, or peripheral resistance responses at
      rest or during HUT in any of the groups. These results suggest that 6 months of
      endurance training, alone or in combination with selected resistance exercises,
      is not detrimental to blood pressure controlling mechanisms to head-up tilt in
      the elderly.

PMID- 7712691
TI  - Day-to-day variability of cardiac autonomic regulation parameters in normal
      subjects.
AB  - We examined the reproducibility of day-to-day variability in cardiovascular
      autonomic nervous function parameters (classical clinical tests and domain
      analysis of heart rate variability) in four healthy men during a period of 1
      working week. The results did not show any significant difference in any of the
      parameters over the five repeated measurements. The maximum-minimum difference as
      percentage of the mean was under 15% for expiration to inspiration (E/I) ratio,
      Valsalva ratio, tachycardia ratio, 30/15 ratio, acceleration index and brake
      index; about 45% for baroreflex sensitivity for systolic and diastolic blood
      pressure and for root mean square difference (RMSSD) of successive R-R intervals;
      about 65-85% for low and high frequency bands, total power and medium to high
      frequency ratio; and about 125% for medium frequency band. The intraclass
      correlation coefficient (ICC) values showed that the agreement for classical
      autonomic parameters (except for brake index) was good. ICC for RMSSD, baroreflex
      sensitivity for systolic blood pressure and the spectral estimates of heart rate
      variation were less good. Coefficient of variation (CV) was 4% for E/I ratio, 2%
      for 30/15 ratio, 6% for Valsalva, 3% for tachycardia ratio, 4% for acceleration
      index and 5% for brake index. CV for baroreflex sensitivity and for RMSSD was
      about 20%. It is concluded that the variation in baroreflex sensitivity is
      clearly larger than in the classical autonomic nervous function parameters. One
      minute fixed pace breathing period seems to be too short to allow reproducible
      measurement of RMSSD and the spectral parameters of heart rate variation.
      Learning effect could be excluded.

PMID- 7712692
TI  - Comparison of two methods to assess the tissue/blood partition coefficient for
      xenon in subcutaneous adipose tissue in man.
AB  - A new method to calculate the tissue/blood partition coefficient (lambda) for
      xenon in studies on the subcutaneous adipose tissue blood flow was compared with
      a previously reported method based on local skinfold thickness (lambda LST). The
      former method included needle biopsies from the abdominal and femoral
      subcutaneous adipose tissue, and the mean fat cell diameter was measured (lambda
      ECT). The extracellular tissue fraction in subcutaneous tissue was then estimated
      from a diagram. The tissue lipid content was approximated to equal the relative
      intracellular volume and Ostwald's solubility coefficients for 133Xe, based on
      the distribution of xenon in lipid, albumin and 0.9% saline were applied.
      Estimated lambda-values based on needle biopsies from the abdominal site were:
      8.6 +/- 0.1 versus 9.9 +/- 0.4 ml g-1 (mean +/- SE) (P < 0.05) and from the
      femoral site: 9.1 +/- 0.1 versus 9.6 +/- 0.2 in lean (n = 10) and obese subjects
      (n = 10), respectively. The corresponding lambda-values obtained from skinfold
      measurements were: 6.2 +/- 0.5 versus 11.0 +/- 0.4 (P < 0.001) and 6.9 +/- 0.3
      versus 11.4 +/- 0.4 (P < 0.001) in lean and obese subjects, respectively. Pooled
      lambda LST-values correlated positively with estimated adipose tissue blood flow
      (ATBF) (r: 0.34, P < 0.05, n = 40) whereas no such correlation was found for
      lambda ECT-values. In conclusion, a new method is presented which may allow an
      accurate determination of, and which may lead to reliable data on, subcutaneous
      ATBF in both lean and obese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712693
TI  - 99mTc-MAG3 kinetics in the normal pig. A comparison to 131I-OIH and 125I
      iothalamate after single injection and during continuous infusion.
AB  - An invasive comparative study of some pharmacokinetic aspects of 99mTc
      mercaptoacetyltriglycine (MAG3), 131I-orthoiodohippurate (OIH), and 125I
      iothalamate (iothalamate) was performed in six pigs 0-150 min after a
      simultaneous single injection (SI) and during a subsequent 90 min of continuous
      infusion (CI). The total plasma clearance and the renal clearance of MAG3 were
      about 75% that of OIH. The renal clearance of MAG3 was about 2 1/2 times the
      glomerular filtration rate. The distribution volume of MAG3 was 71% that of
      iothalamate and only 47% that of OIH. There was a significant hepatic plasma
      clearance of MAG3 of 5.9 ml min-1 and 3.9% of the injected dose was excreted in
      the bile. HPLC analysis revealed that technetium was excreted in urine and bile
      mainly labelled to MAG3. The average red blood cell (RBC) binding after single
      injection/during continuous infusion was 1.0%/2.3% for MAG3, 13.5%/9.0% for OIH,
      and 3.1%/5.3% for iothalamate. The binding of OIH to RBC in arterial blood
      increased from 8% at 1 min post-injection to 21% at 150 min post-injection. The
      RBC binding was higher in the renal vein, indicating incomplete back diffusion
      from RBC to plasma. The protein binding was 90% for MAG3, 49% for OIH and 16% for
      iothalamate. The renal plasma extraction of MAG3 was constant but significantly
      smaller after SI (0.54) than during CI (0.62). Following SI, the renal plasma
      extraction of OIH decreased continuously from 0.85 to 0.52, 3-150 min post
      injection. On the average there was no significant difference in renal plasma
      extraction after SI and during CI of either OIH (0.72 versus 0.77) or iothalamate
      (0.26 versus 0.27). It is concluded that MAG3 is preferential to OIH as a tracer
      for renal function studies using a single injection technique mainly due to the
      constant renal extraction of MAG3.

PMID- 7712694
TI  - Plasma endorphin species during dynamic exercise in humans.
AB  - beta-Endorphin is metabolized to gamma- and alpha-endorphin. In order to evaluate
      endorphin metabolism during exercise, radioimmunoassay blood levels of alpha-,
      beta- and gamma-endorphins were recorded during exercise for 2 h on a cycling
      ergometer in 12 endurance-trained and 11 untrained male subjects. In untrained
      subjects, mild exercise (49 +/- 4% VO2max, mean +/- SD) did not show an increase
      in plasma beta-endorphin, while the levels of its metabolites rose. No changes
      were noted in the endurance-trained subjects. More intensive exercise (66 +/- 6%
      VO2max in untrained and 57 +/- 7% VO2max in trained subjects) resulted in an
      increase in beta-endorphin concentration in association with elevation of the
      alpha-endorphin level. While before and during exercise the beta-endorphin levels
      did not differ significantly between athletes and untrained subjects, the levels
      of gamma- and alpha-endorphins, as well as the molar ratios alpha/beta and
      gamma/beta, were significantly higher in untrained subjects. In conclusion, blood
      levels of beta-endorphin metabolites in the resting state and during exercise are
      dependent on previous training. In untrained subjects, mild exercise may result
      in accumulation of gamma- and alpha-endorphins in blood without a concomitant
      change in beta-endorphin level.

PMID- 7712695
TI  - Cardiovascular and hormonal responses to anaphylactic shock in the pig.
AB  - Cardiovascular and hormonal responses to anaphylactic shock were evaluated in
      anaesthetized pigs sensitized by natural exposure to Ascaris suum as verified by
      antibodies. In six animals with such antibodies, Ascaris antigen injection
      produced a plasma histamine increase of 52 (42-196) fold (median and range; P <
      0.05), while four pigs without such antibodies served as controls with only
      insignificant increases in histamine. In the anaphylactic group, two of the
      animals died during the investigation due to cardiovascular collapse. In the
      sensitized pigs resting heart rate (HR), 104 (86-118) beats min-1, increased to
      204 (164-240) beats min-1 as mean arterial pressure (MAP) decreased from 94 (83
      102) to 45 (31-90) mmHg (P < 0.05). In contrast, the non-sensitized pigs
      maintained the resting HR of 101 (79-113) beats min-1, as MAP decreased to 50 (41
      97) mmHg (P < 0.05). In the sensitized group systemic vascular resistance (SVR)
      fell from 1114 (843-1811) to 990 (588-1173) dyne s-1 cm-5 and then increased to
      3617 (2593-4166) dyne s-1 cm-5, while in the control group there was only a
      reduction to a minimum value of 730 (458-1307) dyne s-1 cm-5 (P < 0.05). Thoracic
      electrical impedance increased only in the sensitized group [from 28.3 (24.7
      31.4) to 29.9 (24.0-31.4)], indicating central volume depletion. Plasma
      catecholamines increased markedly only in the sensitized pigs, and plasma
      pancreatic polypeptide, vasopressin, aldosterone and renin responses confirmed to
      those established during central hypovolaemia. During anaphylaxis, this study
      demonstrated cardiovascular responses similar to those established during a major
      blood loss. However, as indicated by plasma catecholamines, sympathetic activity
      was many times that previously demonstrated during haemorrhage, and
      sympathoactivation may explain the marked vasoconstriction noted in the
      sensitized pigs.

PMID- 7712696
TI  - A comparison between two exercise tests on cycle; a computerized test versus the
      Astrand test.
AB  - Two submaximal cycle ergometer test methods, the Astrand nomogram test and a
      computerized two-point extrapolation test (Cat Eye ergociser, commercially
      available), were compared in order to determine agreement and repeatability of
      estimates of maximum oxygen consumption (VO2max). Twenty healthy women, divided
      into two groups of ten according to their age (mean 35.3 and mean 46.9),
      performed test-retest with each method. In both methods the VO2max was estimated
      from workload and the corresponding heart rate. The correlation between the
      VO2max using the two methods was high (r = 0.85, P < 0.001). Some of the
      estimates derived from the computerized test had large errors, which reduced the
      agreement between the tests. The variation (2SD), expressed in per cent of mean
      VO2max was 19% for the Astrand test and 34% for the computerized test.
      Furthermore, the computerized test underestimated the VO2max with approximately 5
      ml kg-1 min-1 compared with the Astrand test. Due to this underestimation and the
      greater variation of the VO2max in the computerized test, it is not recommended
      to use the two methods interchangeably in clinical practice.

PMID- 7712697
TI  - Comparing the incidence of lower extremity amputations across the world: the
      Global Lower Extremity Amputation Study.
AB  - A substantial proportion of lower extremity amputations (LEAs), particularly in
      people with diabetes, are thought to be preventable by the provision of
      appropriate health care. Information on the incidence of LEAs which is accurate,
      up-to-date, and comparable cross-sectionally and longitudinally is essential to
      guide and monitor interventions aimed at their prevention. Current information on
      the incidence of LEAs is limited and differences between studies in case
      definition, presentation of rates, level of ascertainment, and population age
      structure often make meaningful comparisons impossible. To remedy this situation
      the global LEA study has been established. The study is designed to compare the
      incidence of LEAs over time within and between communities across the world. The
      methodology includes adherence to a standard definition of LEA, standardized
      methods of data collection with built-in quality control, and correction for
      under-ascertainment of cases (using capture-recapture methodology). Centres
      wishing to take part in the study must be able to identify a study population of
      at least 250,000, have reasonably up-to-date population numbers by age and sex,
      and be prepared to stay in the study for at least 2 years. A study registration
      form (Appendix 1) is provided.

PMID- 7712698
TI  - The history of the diabetic foot.

PMID- 7712699
TI  - Thinness at birth and glucose tolerance in seven-year-old children.
AB  - Adults who had low birthweight and were thin at birth have an increased risk of
      Type 2 diabetes and impaired glucose tolerance. To discover whether thinness at
      birth is associated with reduced glucose tolerance in children, 250 7-year-old
      children underwent an abbreviated oral glucose tolerance test. Children who were
      thin at birth, as measured by a low ponderal index (birthweight length-3) had
      higher plasma glucose concentrations. Plasma glucose concentration 30 min after a
      glucose load rose by 0.07 mmol l-1 (95% confidence interval 0.00 to 0.14; p =
      0.04) for every unit (kg m-3) fall in ponderal index. Children in the lowest
      quarter of the distribution of ponderal index (23 kg m-3 or less) had a mean 30
      min plasma glucose concentration of 8.49 mmol l-1 compared to a mean of 7.97 mmol
      l-1 for those in the highest quarter (> 27.5 kg m-3). These associations were
      independent of duration of gestation, gender, social class or the child's current
      weight. This is consistent with the hypothesis that Type 2 diabetes originates in
      utero.

PMID- 7712700
TI  - Undiagnosed glucose intolerance in the community: the Isle of Ely Diabetes
      Project.
AB  - The Isle of Ely Diabetes Project is a prospective population-based study of the
      aetiology and pathogenesis of Type 2 diabetes mellitus. Between 1990 and 1992,
      1156 subjects aged between 40 and 65 years underwent a standard 75 g oral glucose
      tolerance test (OGTT). A total of 1122 individuals who were not known to have
      diabetes completed the test and were classified according to WHO criteria; 51
      subjects (4.5%) had previously undiagnosed diabetes and 188 (16.7%) had impaired
      glucose tolerance. The subjects with newly diagnosed glucose intolerance were
      significantly older, more obese, and shorter than those with normal glucose
      tolerance. Blood pressure, cholesterol, triglyceride, and LDL-cholesterol
      concentrations were elevated and HDL-cholesterol levels were lower among those
      with abnormal rather than normal glucose tolerance. In multiple regression
      analyses stratified by gender and including age, body mass index, and the waist
      hip ratio as covariates, there were significant differences between those with
      normal and abnormal glucose intolerance in blood pressure, triglyceride, and HDL
      cholesterol, but not total or LDL-cholesterol. In both male and female subjects,
      height had a significant independent negative association with the plasma glucose
      at 120 min after administration of oral glucose (standardized beta coefficient = 
      0.12, p < 0.01).

PMID- 7712701
TI  - Skin capillary circulation is more impaired in the toes of diabetic than non
      diabetic patients with peripheral vascular disease.
AB  - The aim of the present study was to investigate if diabetes negatively influences
      the skin microvascular reactivity in the toes of patients with peripheral
      vascular disease (PVD). Twenty healthy subjects, 20 diabetic, and 20 non-diabetic
      patients with PVD participated. One foot in each subject was investigated. The
      patient groups were matched for age, sex, and toe pressure. The capillary blood
      cell velocity in the nailfold of the great toe was investigated by
      videophotometric capillaroscopy, and the total skin microcirculation within the
      same area by laser Doppler fluxmetry. Capillary blood cell velocity and laser
      Doppler flux were studied during rest, and following a 1 min arterial occlusion
      at the toe base. The skin microvascular reactivity was impaired in both diabetic
      and non-diabetic patients. In the diabetic patients the disturbances were mainly
      seen in the capillaries, and the capillary blood flow was severely reduced during
      reactive hyperaemia (p < 0.01). In contrast, the total skin microcirculation was
      normal, indicating that sufficient blood reaches the area, but does not come out
      into the capillaries. The ratio between capillary blood cell velocity and laser
      Doppler flux, representing the distribution of blood between nutritional and non
      nutritional blood compartments, was reduced in the diabetic patients (p < 0.05).
      These findings may contribute to the higher risk for development of chronic foot
      ulcers in diabetic patients with PVD.

PMID- 7712702
TI  - Night blood pressure: relation to organ lesions in microalbuminuric type 1
      diabetic patients.
AB  - Ambulatory blood pressure was measured in 23 microalbuminuric Type 1 diabetic
      patients without hypertension. Nine patients had a reduction in mean arterial
      blood (MAP) pressure at night < 10% of their day-time value (non-dippers). The
      following parameters were measured: glomerular filtration rate (GFR), overnight
      urinary excretion of albumin (UAE), sodium and potassium, left ventricular
      dimensions, extracellular volume (ECV), plasma aldosterone, and arginine
      vasopressin (AVP). Night-time MAP was 11 mmHg lower in patients designated as
      dippers than in non-dippers. Day-time MAP was similar in dippers (98 +/- 5 mmHg)
      and non-dippers (99 +/- 8 mmHg, NS). No statistical significant difference was
      found for UAE in dippers (geometric mean, x/- tolerance factor, microgram min-1)
      (72 x/- 2.1) vs non-dippers (63 x/- 2.1), for left ventricular mass index (63 +/-
      12 vs 59 +/- 10 g m-2), or for GFR (134 +/- 19 vs 148 +/- 22 ml min-1).
      Aldosterone and AVP were lower in non-dippers (p < 0.05) and a negative
      correlation in all patients was noticed between ECV and aldosterone (rho = -0.50,
      p < 0.05). Sodium and potassium excretion and ECV were indistinguishable between
      the groups. We conclude (1) that impaired reduction of night blood pressure does
      not seem to be associated with more signs of renal or cardiac lesions and (2)
      that the lower aldosterone and AVP in non-dippers may counteract volume
      expansion.

PMID- 7712703
TI  - Cigarette smoking and free radical activity in young adults with insulin
      dependent diabetes.
AB  - Cigarette smoke is potentially capable of generating a high free radical load in
      the body and many patients with diabetes are smokers. This study was designed to
      investigate the relationship between long-term smoking and free radical activity
      in young adult insulin-dependent diabetic patients with no evidence of
      macrovascular disease. Eight-five patients (48 male) aged 17-40 years were
      studied. Mean duration of diabetes was 10.5 years (0.08-33) and 39 were cigarette
      smokers. All had normal serum creatinine levels. The free radical markers
      measured were: thiobarbituric acid reactive substances, glutathione peroxidase,
      and superoxide dismutase. No significant differences in thiobarbituric acid
      reactive substances, glutathione peroxidase, or superoxide dismutase, were found
      between the diabetic smokers and non-smokers. Also no difference was found
      comparing the diabetic patients with 40 non-diabetic control subjects (20
      smokers). Persistent albuminuria was present in 16 patients (10 microalbuminuria)
      and free radical marker concentrations in these subjects were similar to the
      normoalbuminuric patients. This data suggests that any increase in free radical
      activity due to cigarette smoke is adequately scavenged in young adults with
      diabetes who are free of significant macrovascular disease.

PMID- 7712704
TI  - Blood rheology and albumin excretion in diabetic pregnancy.
AB  - Blood rheology is altered in diabetes and also in non-diabetic pregnant women.
      The cumulative effect of hyperfiltration, abnormal rheology of pregnancy, and
      diabetes could be one mechanism contributing to increased intraglomerular
      pressure and albuminuria in diabetic pregnancy. We conducted a prospective study
      of 22 Type 1 (insulin-dependent) diabetic patients and 22 non-diabetic women to
      determine if there was an association of altered blood rheology on glomerular
      function in diabetic pregnancy. Albumin excretion showed no increment with
      increasing gestation and was similar in diabetic and non-diabetic women
      throughout pregnancy (first trimester: 5.0 (3.0-14.0) vs 5.8 (3.7-10.7) mg l-1, p
      = 0.89; second trimester: 6.0 (5.0-12.0) vs 5.1 (3.6-10.4) mg l-1, p = 0.25;
      third trimester: 7.5 (3.5-16.0) vs 4.9 (2.9-7.3) mg l-1, p = 0.18). Red cell
      aggregation index increased in both groups between the first and third trimesters
      (diabetic patients: mean difference 2.0; Cl: 1.0-2.9, p = 0.003, and control
      patients: mean difference 2.3, Cl: 1.0-3.5, p = 0.002). Fibrinogen levels were
      significantly higher between the third and first trimesters in diabetic patients
      (mean difference 0.7, Cl: 0.2-1.3 g l-1, p = 0.006). Pregnancy, therefore, was
      associated with increased red cell aggregation, related in part to increased
      fibrinogen levels but the extent of change was similar in diabetic and
      nondiabetic women and appeared to have no adverse effect on glomerular function
      in pregnant insulin-dependent diabetic women.

PMID- 7712705
TI  - Insulin secretion and sensitivity in women fulfilling WHO criteria for
      gestational diabetes.
AB  - Abnormalities of insulin secretion rather than insulin sensitivity are described
      in women fulfilling the American criteria for gestational diabetes. We examined
      insulin secretion and insulin sensitivity in 38 women at risk of gestational
      diabetes categorized according to the less stringent WHO criteria, based on the
      75 g oral glucose tolerance test, performed at 24 weeks gestation. Insulin
      sensitivity was assessed at 28 and 36 weeks using the short insulin tolerance
      test. Applying WHO criteria, 18 women had GDM. Age and body mass index of the GDM
      and glucose tolerant women were similar (32.4 +/- 1.1 (SE) vs 32.3 +/- 1.9 yr;
      28.7 +/- 1.5 vs 28.8 +/- 1.7 kg m-2, respectively). Fasting glucose was higher in
      the GDM women than controls (5.1 +/- 0.2 vs 4.5 +/- 0.1 mmol l-1, p < 0.025)
      while fasting insulin was similar (75 +/- 18 vs 90 +/- 16 pmol l-1). The 30-min
      insulin concentration during the OGTT was lower in the GDM women than controls
      (436 +/- 61 vs 788 +/- 152 pmol l-1, p < 0.05), while the insulin sensitivity at
      28 (87 +/- 5 vs 76 +/- 5 mumol l-1 min) and 36 weeks (73 +/- 8 vs 76 +/- 8 mumol
      l-1 min) was similar. A negative correlation existed between the 30-min insulin
      and 120-min glucose concentration during the OGTT (Rho -0.328, p < 0.05). The WHO
      criteria for GDM identify women with similar abnormalities of insulin secretion
      as the more stringent American criteria.

PMID- 7712707
TI  - Factors influencing the low density lipoprotein profile in type 2 diabetic
      patients.
AB  - The lipoprotein distribution profile was examined in Type 2 (non-insulin
      dependent) diabetic patients (n = 52), with particular emphasis on factors
      influencing low density lipoproteins (LDL). Triglycerides were negatively
      correlated with LDL-2 (r = 0.34, p < 0.05) and positively correlated with
      smaller, denser LDL-3 (r = 0.57, p < 0.001). This yielded a highly significant,
      negative correlation between triglycerides and the LDL-2/LDL-3 mass ratio (r = 
      0.59, p < 0.001) which is an indication of the presence of smaller LDL particles.
      Parameters of glycaemic control, in the form of fasting blood sugar and glycated
      haemoglobin (HbA1c), were also negatively correlated with the LDL-2/LDL-3 mass
      ratio in univariate analyses; both remained significantly correlated with the
      mass ratio when corrected for triglycerides. Stepwise multiple regression
      analysis identified a three-parameter model comprising triglycerides, HbA1c, and
      high density lipoprotein cholesterol as best defining the variations in the LDL
      2/LDL-3 mass ratio (adjusted r2 = 0.52). These observations are consistent with
      an independent impact of diabetes on the LDL distribution profile and the
      possibility that the latter may be subjected to multiple pathological influences
      in diabetic patients.

PMID- 7712706
TI  - Risk of diabetes in offspring of parents with non-insulin-dependent diabetes.

PMID- 7712708
TI  - Insulin resistance with respect to lipolysis in non-diabetic relatives of
      European patients with type 2 diabetes.
AB  - Type 2 diabetes is characterized by resistance to insulin action of glucose
      metabolism and lipolysis. First-degree relatives of diabetic patients are at
      increased risk of developing diabetes themselves and early metabolic
      abnormalities in these relatives may represent primary defects in the
      pathogenesis of diabetes. Our previous work has demonstrated impaired suppression
      of lipolysis after an oral glucose load in glucose-tolerant relatives of Asian
      origin, but not in European relatives. To investigate whether a more subtle
      defect exists in the European population we studied 8 first-degree relatives of
      European patients and 9 matched control subjects. All had normal glucose
      tolerance. Glycerol and glucose turnovers were measured using a primed constant
      infusion of the stable isotopic tracers [1,1,1,2,3(2)H5] glycerol and [6,6(2)H]
      glucose, basally and in response to a very low dose insulin infusion (0.005 units
      kg-1 h-1). The relatives had higher basal insulin concentrations (median (range):
      49 (30 to 113) vs 28 (18 to 66) pmol 1(-1), p < 0.05) compared to controls, but
      basal glycerol and glucose turnovers and plasma concentrations of glycerol,
      glucose, and non-esterifed fatty acids (NEFA) were similar. Following insulin,
      the suppression of glycerol appearance in the circulation measured isotopically
      was significantly less complete in the relatives compared with controls (mean
      change +/- SEM: + 0.06 +/- 0.21 vs - 0.51 +/- 0.16 mumol kg-1 min-1, p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712709
TI  - 'Hospital hyperglycaemia'; perception or reality?
AB  - Patients' perceptions that clinic fasting blood glucose measurements in Type 2
      diabetes are artefactually high were investigated. Eighteen men and 14 women in
      the Salford cohort of the United Kingdom Prospective Diabetes Study (UKPDS) with
      a median age of 51 (range 37-69) years measured their fasting blood glucose
      concentration at home with visually read sticks or meters; they then collected
      capillary blood into fluoride tubes both at home and in clinic after a median
      lapse of 77 (range 25-173) min. The clinic samples were measured immediately and
      after a time lapse equivalent to the time taken to reach clinic to control for
      continued glycolysis in the home sample. Mean fasting blood glucose was 5.9 +/-
      1.9 mmol 1(-1) by the patients' own measurement and 6.0 +/- 1.8 mmol 1(-1) on the
      home collected sample compared with 6.2 +/- 2.0 mmol 1(-1) and 6.1 +/- 2.0 mmol
      1(-1) on the hospital immediate and time-lapsed measurements, respectively (p >
      0.05 for all comparisons between home and hospital measurements); although there
      were no systematic differences, occasional measurements differed more than 2 mmol
      1(-1). These data support the use of the fasting blood glucose level as a stable,
      patient-independent measure of glycaemic control in Type 2 diabetes.

PMID- 7712712
TI  - The diabetic foot 1994.

PMID- 7712711
TI  - DIAMOND: a computerized system for the management and evaluation of district-wide
      diabetes care.
AB  - A computerized diabetic clinic management system, DIAMOND, has been developed
      with the collaboration of local general practitioners (GPs) to assist
      communication about diabetic patients across the district. DIAMOND is written in
      a Windows format using Microsoft Access and its dataset is in line with BDA and
      Diabcare recommendations. DIAMOND is user-friendly and includes displays and help
      messages throughout and does not require advanced computer knowledge. The main
      index contains two primary tables: a patient registration table with demographic
      data and an episode table with clinically important physical and biochemical
      measures. All entered data are coded to facilitate audit and an audit function,
      which automatically presents data, either numerically or graphically, is included
      in the report facility. DIAMOND also incorporates a system for patient education
      and training (PEATS) which may be operated by a health professional or the
      patient. Over 4500 patients in Newham are presently registered on DIAMOND with in
      excess of 15,000 episodes. Evaluation of this information is providing important
      clinical information both within individual GP practices and district-wide to
      assist future plans for health care provision.

PMID- 7712710
TI  - Aetiopathogenesis and management of impotence in diabetic males: four years
      experience from a combined clinic.
AB  - The contribution of organic and psychogenic factors in the aetiopathogenesis of
      impotence was studied in a large number of diabetic males, to develop an
      algorithm for its management. We examined 110 consecutive patients who were
      referred to the Impotence Clinic of the Diabetes Centre. All patients were
      initially evaluated by a diabetologist and then underwent psychosexual assessment
      by a specialized psychiatrist. Patients with primarily organic disease were
      referred to a urologist for further management while those with psychogenic
      impotence received psychosexual counselling. Peripheral neuropathy was present in
      71 (65%) and two or more autonomic tests were abnormal in 22 (20%) patients.
      Neuropathy was the only cause detected in 29 (27%) patients, the main cause in 22
      (20%), and contributing, but not the main factor, in 20 (18%). Psychogenic
      factors were the only cause detected in 12 (11%) patients, the main cause in 26
      (24%) and contributed in 19 (17%). Marital disharmony, medical treatment, and
      peripheral vascular disease were the main aetiopathogenic factors in the
      remaining cases. Psychosexual counselling resulted in successful intercourse in
      17 (60%) out of the 24 treated patients and papaverine injections in 31 (61%) out
      of 56 treated patients. It is concluded that although organic factors are mainly
      responsible for the development of impotence in diabetic males, psychological
      factors contribute significantly and psychosexual assessment and counselling are
      essential adjuncts to its management. Treatment with papaverine injections is
      generally inexpensive and effective to overcome the multifactorial causes of
      erectile dysfunction in this population. An algorithm which may facilitate the
      investigation and treatment of impotent diabetic males is proposed.

PMID- 7712713
TI  - First parallel Medical and Scientific Section together with Education and
      Professional Care Section (MSS/EPCS) of the BDA: Autumn 1994. Lancaster, UK.

PMID- 7712715
TI  - Dialysis membranes: structure and predictions. International workshop
      proceedings. Marseille, June 25, 1994.

PMID- 7712716
TI  - Biocompatibility and the clinical choice of dialysis membranes.

PMID- 7712717
TI  - Composition of polymer membranes for therapies of end-stage renal disease.

PMID- 7712718
TI  - Long-term morbidity: hemofiltration vs. hemodialysis.

PMID- 7712714
TI  - Evolution of hemodialysis membranes.

PMID- 7712720
TI  - Classification of dialysis membranes by performance.

PMID- 7712719
TI  - Long-term results: cellulosic vs. synthetic membranes.

PMID- 7712721
TI  - Evaluation of dialysis membrane-blood compatibility: experimental methods.

PMID- 7712723
TI  - Efficiency and biocompatibility of membranes.

PMID- 7712722
TI  - Ultrafiltration and depurative parameters.

PMID- 7712724
TI  - Phagocytic function in dialysis.

PMID- 7712726
TI  - Amyloidosis in patients with end-stage renal failure: uraemia associated or
      dialysis related?

PMID- 7712725
TI  - Dialysis and the immune system.

PMID- 7712727
TI  - Confocal microscopy: into the clinic.

PMID- 7712729
TI  - Bilateral linear corneal ectasia. An unusual case and its surgical management.
AB  - A 24-year-old man presented with narrow, linear areas of thinning situated
      horizontally in the upper part of both corneas. These areas were associated with
      progressive corneal ectasia, causing high degrees of "against the rule"
      astigmatism. By excising the affected areas, the refractive error was
      significantly improved in both eyes. Features of the disease suggested that the
      condition was related to the other ectatic corneal dystrophies.

PMID- 7712728
TI  - Diagnosis of Acanthamoeba keratitis in vivo with confocal microscopy.
AB  - We present eight cases of Acanthamoeba keratitis. In each case; the Acanthamoeba
      organisms were visualized in the epithelium and anterior stroma using tandem
      scanning confocal microscopy. The organisms were highly reflective, ovoid, and
      were 10-25 microns in diameter. The Acanthamoeba organisms in the human corneas
      were identical in size and shape to Acanthamoeba organisms on an agar plate
      visualized with the same confocal microscope. Confocal microscopy is a useful
      method for identifying Acanthamoeba organisms in vivo within the corneal
      epithelium and anterior stroma.

PMID- 7712730
TI  - The need to specify source of Schirmer's tear test strip.

PMID- 7712731
TI  - Results of penetrating keratoplasty in CHED. Congenital hereditary endothelial
      dystrophy.
AB  - Congenital hereditary endothelial dystrophy is characterized by a diffuse
      bilateral corneal opacity (edema). Its inheritance has been reported to be both
      autosomal recessive and dominant. All our cases seemed to be autosomal recessive.
      There seems to be a prevalence of the recessive gene in the Iranian population.
      The dystrophy might be misdiagnosed as congenital glaucoma, as in several of our
      cases. We have operated on 37 eyes of 21 patients during the past 10 years. Our
      visual and anatomical success rate has been very good, with 92% clear grafts and
      only an 8% rejection rate, in contrast to poor prognosis that has been previously
      reported. In children, suture removal should be started 3 months postoperatively.
      Partial amblyopia was preexistent in all cases, but deep amblyopia was not
      common.

PMID- 7712733
TI  - Quantitative assessment of anteroposterior keratocyte density in the normal
      rabbit cornea.
AB  - The anteroposterior keratocyte density distribution in the rabbit cornea was
      measured. Unsectioned tissue blocks from the central cornea of five rabbits were
      stained with propidium iodide and imaged using a Leica laser scanning confocal
      microscope. A z-series of images was acquired confocal microscope. A z-series of
      images was acquired in each sample, from anterior to posterior stroma in either 3
      or 8-microns steps. Software was developed to allow interactive marking of the
      keratocyte nuclei within each section of the z-series and for calculating cell
      density. For convenience, cell density was expressed as the number of cells per
      corneal volume element (CVE), where CVE is a newly defined volume unit with x, y,
      and z dimensions of 250, 250, and 10 microns, respectively. The calculated
      keratocyte density was 20.2 +/- 1.0 cells/CVE (n = 5), which is equivalent to
      32,360 +/- 1,660 cells/mm3. The greatest density was underneath the epithelium
      (26.3 +/- 2.5 cells/CVE), the density then decreased linearly with depth to 15.2
      +/- 1.4 cells/CVE; there was a slight increase in density pre-Descemets membrane
      to 18.5 +/- 3.5 cells/CVE. A 30% decrease in cell density over the entire
      anteroposterior stromal thickness was observed. To facilitate statistical
      analysis, the cell density was averaged over 5% thickness intervals from anterior
      to posterior cornea. A significant difference in mean cell density of these
      intervals was found (ANOVA, n = 20, p < 0.01). To further assess the density
      distribution, linear regression analysis was performed. A significant correlation
      was found between keratocyte density and stromal depth (R = -0.94, n = 20, p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712735
TI  - Current clinician's opinions on risk factors in corneal grafting. Results of a
      survey among surgeons in the eurotransplant area.
AB  - During 1992 a questionnaire was sent to 57 cornea transplant centers in the
      Eurotransplant area, i.e., the Netherlands, Germany, Belgium, and Austria.
      Questions included the number of grafts transplanted in each center in 1991, the
      indications for cornea transplants, and surgeons' opinions on risk factors and
      indications for human leukocyte antigen (HLA)-matched grafts. A response rate of
      89% (51 of 57) was achieved. The total number of grafts in the 51 reporting
      centers was 2,156 [average 42 (range: 3-303)]. In 19.3% of the cases HLA-matched
      donor tissue was used (range: 0-64%). Matched transplants were performed in high
      risk cases. The term high-risk is not standardized by any means. Foremost, HLA
      matched donor corneas were requested for regraft after immunologic failure of a
      previous transplant and in cases showing more than two quadrants of deep stromal
      vascularization. This survey has shown important differences in management of
      high-risk cases: variance in indications for HLA-matched grafting and no
      consistency in the weighing of the importance of HLA-A, HLA-B, and HLA-DR
      antigens nor consistency in the use of information on circulating antibodies. For
      proper allocation of available donor tissue for corneal transplants in the
      Eurotransplant area, a mutually accepted protocol defining indications for
      matched grafting is needed.

PMID- 7712732
TI  - Results of alloplastic tube shunt procedures before, during, or after penetrating
      keratoplasty.
AB  - The association of glaucoma and penetrating keratoplasty presents a difficult
      management problem, particularly when medical therapy and conventional glaucoma
      surgery have failed. We have found alloplastic tube shunt surgery to be an
      effective method for intraocular pressure control in glaucomatous eyes subjected
      to penetrating keratoplasty. We report 46 patients who underwent alloplastic tube
      shunt implantation before (13 patients, group A), in combination with (17
      patients, group B), or after (16 patients, group C) penetrating keratoplasty. All
      groups had significantly lowered intraocular pressure postoperatively. The most
      common complication was graft failure, in 31% of patients in group A, 29% in
      group B, and 44% in group C. Other postoperative complications and results
      including visual outcome are reviewed. Because the management of advanced
      glaucoma in patients undergoing keratoplasty is difficult, alloplastic tube shunt
      implantation should be considered.

PMID- 7712734
TI  - Penetrating keratoplasty with vitreoretinal surgery using the Eckardt temporary
      keratoprosthesis: modified technique allowing use of larger corneal grafts.
AB  - We report our experience with the Eckardt temporary keratoprosthesis including a
      technique modification allowing use of larger corneal grafts. We combined
      penetrating keratoplasty with vitreoretinal surgery using the Eckardt
      keratoprosthesis in 24 eyes of 24 patients in two patient groups: trauma (n = 11)
      and nontrauma (n = 13). Our technique modification involved centering a larger
      partial trephination for the donor cornea around the smaller trephination used
      for the keratoprosthesis. After the keratoprosthesis was removed, we excised host
      cornea graft. With the exception of visual acuity (VA), the outcomes were similar
      for both trauma and nontrauma groups, and combined results were as follows.
      Corneal grafts remained clear in 71% of patients at a mean follow-up period of 16
      +/- 3 (SE) months. For the trauma and nontrauma groups, VA improved in 82 and
      23%, and decreased in 18% and 38.5%, respectively. Postoperative loss of VA was
      due primarily to retinal scarring (47%) and phthisis bulbi (37%). Only one case
      of graft rejection occurred. Postoperatively, the larger corneal grafts (8.0 and
      8.5 mm) were less steep, and residual astigmatism was more easily managed than
      with the "recommended" (7.2 mm) size. CONCLUSIONS: Larger corneal grafts allow
      less astigmatism and a more normal corneal curvature. Theoretical advantages also
      include faster rehabilitation of vision, better predictability for intraocular
      lens implant power calculations, and transplantation of more endothelial cells.
      The Eckardt will continue to be a useful tool and our technique modification
      allowing use of larger corneal grafts should enhance its utility.

PMID- 7712738
TI  - Effect of poloxamer 407 on the adherence of Pseudomonas aeruginosa to corneal
      epithelial cells.
AB  - The effect of poloxamer 407 on Pseudomonas aeruginosa adherence to cultured
      epithelial cells from rabbit corneas was investigated. Three methods of bacterial
      quantification were used to assess P. aeruginosa adherence: scanning electron
      microscopy (SEM) counts, radioactivity counts, and viable bacteria counts.
      Confluent monolayers of rabbit corneal epithelial cells were incubated in
      agitation for 30 min at room temperature with H3-labeled or nonradiolabeled P.
      aeruginosa (10(10) bacteria/ml) in a solution of poloxamer 407 [2% or 4% in
      phosphate-buffered saline (PBS)] or PBS as control. Cell monolayers were washed
      to remove nonadherent bacteria and fixed with 2.5% glutaraldehyde and processed
      for SEM or processed for radioactivity counting or for culture on agar plates.
      The results showed that both solutions of poloxamer 407 inhibited approximately
      75% of the bacterial adherence to epithelial cells (p < 0.05). Similar
      percentages of bacterial inhibition were obtained using the three methods of
      bacterial quantification. The use of an antiadherent agent such as poloxamer 407
      in eye drops could possibly be a prophylactic approach to P. aeruginosa
      keratitis.

PMID- 7712737
TI  - Efficacy and safety of gentamicin and streptomycin in Optisol-GS, a preservation
      medium for donor corneas.
AB  - Increasing reports of gentamicin-resistant bacteria contaminating donor corneas
      and causing endophthalmitis have indicated that preservation of corneal storage
      media with 100 micrograms/ml of gentamicin alone needs reevaluation. We
      investigated the stability and possible cytotoxicity of streptomycin as a
      supplement to gentamicin in Optisol corneal storage medium. The combination of
      gentamicin and streptomycin in Optisol solution was stable at room temperature
      for at least 4 weeks and inhibited the growth of Staphylococcus aureus, S.
      epidermidis, alpha hemolytic streptococci, Streptococcus Group D,
      Propionibacterium acnes, Escherichia coli, and diphtheroids, but not Pseudomonas
      aeruginosa. The addition of vancomycin did not significantly improve the
      antibacterial effectiveness of the gentamicin and streptomycin combination when
      stored at 4 degrees C. The growth of 15 of 20 clinical ocular isolates of Ps.
      aeruginosa was suppressed by the gentamicin-streptomycin combination.
      Streptomycin in concentrations of up to 1,000 micrograms/ml did not decrease the
      mitotic activity of corneal endothelial cells as evaluated by the in vitro
      incorporation of tritiated thymidine or cause cytotoxicity. The addition of 200
      micrograms/ml of streptomycin to Optisol corneal storage medium containing 100
      micrograms/ml of gentamicin may significantly improve activity against gentamicin
      sensitive and gentamicin-resistant contaminants.

PMID- 7712736
TI  - Patient-reported symptoms associated with graft reactions in high-risk patients
      in the collaborative corneal transplantation studies. Collaborative Corneal
      Transplantation Studies Research Group.
AB  - The Collaborative Corneal Transplantation Studies (CCTS) were designed to
      evaluate the effect of donor-recipient histocompatibility matching and cross
      matching on the survival of corneal transplants in high-risk patients. We now
      report on the role of symptoms in the detection of corneal allograft reactions in
      the CCTS and on the relationship between symptom reporting and graft survival.
      The 456 patients transplanted in the CCTS were followed for a minimum of 2 years
      or until graft failure. The follow-up protocol included 11 scheduled examinations
      in the first year, four examinations during the second year, and examinations
      every 6 months thereafter. Interim examinations were performed in response to
      patient-reported symptoms. At every examination, patients were asked specifically
      if they had redness, sensitivity to light, loss of vision, or pain (RSVP). Of the
      456 patients transplanted, 62% had at least one graft reaction. Patients
      diagnosed with reactions at scheduled visits in the first postoperative year were
      2.5 times more likely to report symptoms than those without reactions. Reports of
      red eye and vision loss were strongly associated with allograft reaction.
      However, these symptoms were neither highly sensitive nor specific for reaction
      (sensitivity = 46%, specificity = 70% at 6 months). The severity of reaction
      influenced the reporting of symptoms: 69% of patients with severe reactions
      reported symptoms versus 48% of patients with mild reactions (p < 0.001). The
      only patient characteristic associated with reliable symptom reporting was age,
      with younger patients with reactions being more likely to report
      symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712741
TI  - Corneal epithelium in keratoconus.
AB  - Specular microscopy was employed to study the corneal epithelium of 20
      keratoconus patients (17 male, 3 female, average age 23.9 +/- 6.6 years). The
      patients were divided into three groups based on the severity of the keratoconus;
      early, intermediate, and advanced. Initially, epithelial changes were limited to
      enlargement of the superficial cells. As the disease progressed, elongated cells
      became prominent. Irregularly configurated and nucleated epithelial cells were
      observed in all cases. Morphomeric analysis showed that the mean area of the
      corneal epithelial cells was 906 +/- 203 microns 2 in the early stage, 1,416 +/-
      521 microns 2 in the intermediate stage, and 1,641 +/- 372 microns 2 in the
      advanced stage. The shape factor was 0.32 +/- 0.05, 0.76 +/- 0.22, and 0.81 +/-
      0.17, respectively. Controls were chronic wearers of hard contact lenses without
      corneal pathology. Analysis of their epithelium revealed no abnormalities. This
      finding suggests that the epithelial changes observed in keratoconus are not due
      to the wearing of contact lenses, but rather to the disease itself.

PMID- 7712739
TI  - Growth of human corneal endothelial cells in a serum-reduced medium.
AB  - A new medium composition was established for growth of adult human corneal
      endothelial cells (HCEC) under serum-reduced conditions. Growth assays were
      performed in clonal densities with HCEC using serum-reduced culture conditions.
      The growth-promoting effect of different substances was tested step by step. The
      new serum-reduced medium was compared with the generally used medium supplemented
      with conventional amounts of serum. A culture medium recently described
      (Engelmann K, Bohnke M, Friedl P. Optimization of culture conditions for human
      corneal endothelial cells. In Vitro Cell Dev Biol 1989;25:1065-72) for the long
      term cultivation of human corneal endothelial cells derived from adult donors was
      used as the starting point for the development of a new low-serum medium. It was
      found that the addition to the supplements ascorbic acid, insulin, selenium,
      transferrin, lipids, and fibroblast growth factor to the basal medium F99 (a 1:1
      mixture of Ham's F12 and M199) allowed reduction of the serum content to as low
      as 2%. The new medium formula, called F99sr, showed an improved dose-response
      curve of cell growth to serum content over the range 2-40%. To ensure the
      maintenance of a typical endothelial cell morphology at confluence, the serum
      content should be 5%.

PMID- 7712742
TI  - Long-term results of epikeratoplasty for keratoconus.
AB  - By analysis of outpatient records at the Massachusetts Eye and Ear Infirmary, the
      clinical course of 10 consecutive patients who underwent epikeratoplasty for
      keratoconus was reviewed to determine their clinical and functional status 5
      years after surgery. Eight of 10 patients (80%) had clear, intact lenticules at
      12 months. During a mean follow-up of 67 months (range = 35-101 months), each
      maintained long-term stability of best corrected vision, refractive astigmatism,
      and keratometric astigmatism. The mean uncorrected visual acuity improved from
      20/660 to 20/134, whereas the mean spectacle corrected acuity improved from
      20/260 to 20/30. All but one patient had a spectacle acuity equal to hard contact
      lens acuity. However, no patients were corrected to 20/20 at the end of the
      follow-up period. Refractive and keratometric astigmatism stabilized by 12 months
      (mean = 3.62 and 3.05 D, respectively), and decreased slightly during the longer
      period of follow-up (mean = 2.94 and 2.17 D, respectively). Epikeratoplasty is a
      useful method of visual rehabilitation in highly selected cases of keratoconus in
      which there is no central opacity, preoperative hard contact lens acuity is worse
      than 20/40, the average keratometry is < 60 D, contact lens intolerance is
      present, and in which the patient will tolerate some degree of reduced contrast
      sensitivity and < 20/20 high contrast acuity.

PMID- 7712743
TI  - The effects of age on phosphatic metabolites of the human cornea.
AB  - Phosphatic metabolites from human corneas, pooled into 7 decades ranging from
      ages < 1 year through 79 years, were quantitated using phosphorus-31 magnetic
      resonance (31P MR) spectroscopy. Relative concentrations of phosphorus-containing
      compounds measured included the low-energy metabolites [phosphomonoesters (PME),
      inorganic orthophosphate (Pi), phosphodiesters (glycerol 3-phosphorylethanolamine
      and glycerol 3-phosphorylcholine)] and the high-energy metabolites
      [phosphocreatine (PCr), adenosine triphosphate (ATP), adenosine diphosphate
      (ADP), nucleosidediphosphosugars and the dinucleotides]. Significant linear
      changes attributable to age occur in the relative mole percentage decrease of
      phosphate concentrations of human corneal PME, PCr and ATP, and in the increase
      of Pi. Age-attributable rates of decrease in PME at -0.162 MPP/YR (mole percent
      phosphorus per year), PCr at -0.015 MPP/YR and ATP at -0.487 MPP/YR combined,
      approximate the rate of increase in Pi determined to be +0.729 MPP/YR. Of the
      indices computed from the human corneal spectral data, the ratios of ATP/Pi and
      PME/Pi and the tissue energy modulus were all found to decrease significantly
      with age. These changes in corneal phosphatic metabolites are indicative of an
      overall decline in high-energy metabolism with age.

PMID- 7712744
TI  - Implantation of cilium after corneal transplant: a case report.

PMID- 7712740
TI  - Cytotoxicity of intracameral injection drugs to corneal endothelium as evaluated
      by corneal endothelial cell culture.
AB  - The cell culture method was used to quantitatively evaluate the cytotoxicity to
      porcine corneal endothelial cells by drugs in the usual concentrations of
      intracameral injections (ICI). Time-dependent cytotoxicity of drugs was evaluated
      quantitatively; dye exclusion assay by trypan blue was used as a viability assay;
      and cytotoxicity to corneal endothelium was tested using amphotericin-B,
      amikacin, colistin, sulbenicillin, and cephradine in their original, 10-fold, and
      100-fold ICI concentrations. Original and 10-fold ICI concentrations of
      betamethasone also were used. In original and 10-fold ICI concentrations, only
      amphotericin-B had significant cytotoxicity. In 100-fold ICI concentrations,
      amphotericin-B, colistin, and sulbenicillin had significant cytotoxicity.
      Betamethasone had neither a cytotoxic nor a proliferative effect in its original
      and 10-fold ICI concentrations. A 0.1-fold ICI concentration of amphotericin-B
      also showed 42.75% cytotoxicity to corneal endothelium by monolayer cultured
      cells and the time-dependent cytotoxicity of drugs as a quantitative method is
      efficient and objective.

PMID- 7712745
TI  - Calcareous corneal degeneration: report of two cases.
AB  - Band keratopathy, calcium salts in Bowman's membrane, is the most classic form of
      corneal calcification seen in clinical practice. However, calcareous
      degeneration, calcium deposition involving the full corneal thickness, is rare.
      We reviewed the clinical and histopathological records of two patients with
      severe dry eyes and calcareous corneal degeneration. In each case, complete
      ophthalmic examination and histopathological study were performed. Both patients
      had severe dry eyes, case 1 secondary to graft-versus-host disease and case 2
      secondary to rheumatoid arthritis, and a persistent epithelial defect and
      anterior segment chronic inflammation. Both patients underwent repeated
      penetrating keratoplasties. Histological examination of the corneal buttons
      showed that calcareous corneal degeneration and band keratopathy were coincident
      in both cases. Both patients received postoperative medications for high-risk
      grafting. The mechanisms of corneal calcification may be the same in calcific
      band keratopathy and calcareous corneal degeneration.

PMID- 7712746
TI  - A silver anniversary for the Society of Critical Care Medicine--visions of the
      past and future: the presidential address from the 24th Educational and
      Scientific Symposium of the Society of Critical Care Medicine.

PMID- 7712747
TI  - Selective decontamination of the digestive tract and its effect on antimicrobial
      resistance.

PMID- 7712748
TI  - Defining the role of oxyradicals in the pathogenesis of sepsis.

PMID- 7712750
TI  - Medical futility.

PMID- 7712749
TI  - Is the physician's duty to the individual patient or to society?

PMID- 7712751
TI  - Workforce needs and training in pulmonary and/or critical care medicine.

PMID- 7712753
TI  - Long-term effects of selective decontamination on antimicrobial resistance.
AB  - OBJECTIVE: To determine whether selective decontamination of the digestive tract
      exerts any long-term effects on antimicrobial resistance patterns. DESIGN: A
      surveillance and interventional study comparing the antimicrobial sensitivity
      patterns of clinically important bacterial isolates the year before a 2-yr,
      double-blind, randomized, controlled study of selective decontamination of the
      digestive tract, and for the year thereafter when no use of the regimen was made.
      SETTING: A ten-bed respiratory intensive care unit (ICU) in a 1,200-bed teaching
      hospital. PATIENTS: All 1,528 patients admitted to the ICU over the 4-yr study
      period were included. There were 406 patients admitted in the year before the
      study of decontamination of the digestive tract (65% medical, 23% surgical, and
      12% trauma), of whom 76% required mechanical ventilation. There were 719 patients
      admitted during the 2-yr study of selective decontamination (55% medical, 28%
      surgical, and 17% trauma), of whom 79.6% required mechanical ventilation. There
      were 403 patients admitted in the subsequent year (61% medical, 25% surgical, and
      14% trauma), of whom 76.9% required mechanical ventilation. INTERVENTIONS: We
      performed daily clinical monitoring to detect nosocomial infection, with
      microbiological investigation when clinically indicated, as well as twice-weekly
      routine microbiological surveillance sampling. Antimicrobial susceptibility
      testing using standard laboratory methods was also performed. Selective
      decontamination of the digestive tract included parenteral cefotaxime and oral
      and enteral polymyxin E, amphotericin B, and tobramycin. MEASUREMENTS AND MAIN
      RESULTS: The occurrence rate of nosocomial infection was 20.6%, 16.6%, and 25.3%,
      respectively, in the three study periods. In the year after selective
      decontamination, there was an increase in the occurrence rate of infection (p =
      .005), with an-associated increase in infections caused by the
      Enterobacteriaceae, while a reduction in the level of resistance to the third
      generation cephalosporins were found (p = .07). There was a progressive increase
      in the occurrence rate of infections caused by Acinetobacter species (p = .05).
      Only 11 infections over the 4 yrs were caused by Enterococcus species.
      Staphylococcal infections were uncommon (5.7% of admissions), and the level of
      methicillin resistance did not change. No increase in aminoglycoside resistance
      occurred. CONCLUSION: No long-term effects on antimicrobial resistance or the
      spectrum of nosocomial pathogens could be attributed to the use of selective
      decontamination of the digestive tract over a 2-yr period in a respiratory ICU
      admitting all categories of patients.

PMID- 7712752
TI  - African-American and white patients admitted to the intensive care unit: is there
      a difference in therapy and outcome?
AB  - OBJECTIVE: To evaluate variations in patient characteristics, hospital mortality,
      intensive care unit (ICU) length of stay, and treatment among African-American
      and white patients admitted to the ICU. DESIGN: Prospective, inception cohort
      study. SETTING: Forty-two ICUs at 40 U.S. hospitals, including 26 hospitals that
      were randomly selected and 14 volunteer institutions, primarily large university
      or tertiary care centers. PATIENTS: A consecutive sample of 17,440 ICU
      admissions. MEASUREMENTS AND MAIN RESULTS: Selected demographic, physiologic, and
      treatment information for an average of 415 admissions at each ICU, and payor
      information at 36 of 40 hospitals. Outcomes were compared using the ratio of
      observed to risk-adjusted predicted hospital mortality rate, ICU length of stay,
      and resource use during ICU day 1 and the first seven ICU days. Compared with
      14,006 white patients admitted to the ICU, 2,450 African-American patient
      admissions were significantly (p < .0001) younger, had a higher mean severity of
      disease, and a greater proportion of nonoperative and emergency department
      admissions. African-Americans had fewer life-threatening Acute Physiology and
      Chronic Health Evaluation III (APACHE III) comorbidities, but a higher prevalence
      of severe compromise in activities of daily living, diabetes mellitus, chronic
      renal disease, and intravenous drug abuse. There was no significant racial
      difference in risk-adjusted hospital mortality rate. For African-Americans,
      adjusted ICU length of stay was significantly (p < .0003) shorter, and the first
      7 days of resource use was significantly (p < .0004) lower, but the differences
      were small (3% to 4%). CONCLUSIONS: After adjusting for variations in patient
      characteristics at ICU admission, race has no significant effect on hospital
      survival. The small but statistically significant differences in adjusted ICU
      length of stay and resource use could indicate undertreatment for African
      Americans or overtreatment for whites.

PMID- 7712755
TI  - Increased intestinal permeability following blunt and penetrating trauma.
AB  - OBJECTIVES: To determine changes in the absorption of lactulose and mannitol in
      patients undergoing laparotomy following blunt or penetrating trauma and to
      correlate any changes in permeability with the severity of injury. DESIGN:
      Nonrandomized study within patient control. PATIENTS: Consecutive patients
      admitted to the trauma unit following blunt or penetrating trauma with intra
      abdominal injuries warranting emergent celiotomy and jejunal access.
      INTERVENTIONS: Intestinal permeability was measured in 18 patients within 48 hrs
      post-trauma by the bolus infusion into the jejunum of nonmetabolized probe
      molecules, lactulose (molecular weight of 342) and mannitol (molecular weight of
      182). Because several patients did not tolerate the bolus infusion, a 3-hr
      continuous infusion of the probe molecules was used in the last eight patients
      entered into the study. Intestinal permeability was reassessed before discharge
      or on days 10 to 12. MEASUREMENTS AND MAIN RESULTS: There was a decrease in
      urinary lactulose excretion and the lactulose/mannitol ratio between the initial
      posttrauma measurement and the follow-up permeability measurement using both the
      bolus infusion (lactulose: initial 0.13 +/- 0.032 vs. follow-up 0.047 +/- 0.012
      mmol/6 hrs, p < or = .05; lactulose/mannitol: initial 0.067 +/- 0.012 vs. follow
      up 0.044 +/- 0.012, p = .11) and the continuous infusion (lactulose: initial
      0.044 +/- 0.013 vs. follow-up 0.014 +/- 0.002 mmol/2 hrs, p < or = .05;
      lactulose/mannitol: initial 0.055 +/- 0.020 vs. follow-up 0.015 +/- 0.007, p < or
      = .05). Urine excretion of mannitol was not significantly different between
      posttrauma and follow-up measurements of intestinal permeability, regardless of
      the technique used to infuse the lactulose and mannitol. Although the decrease in
      lactulose and the lactulose/mannitol ratio was significant, only one third of the
      patients had dramatically increased permeability at the initial measure.
      Abdominal Trauma Index and Injury Severity Score did not correlate with urinary
      lactulose excretion or the lactulose/mannitol ratio. Patient tolerance of jejunal
      administration of lactulose and mannitol was better, using a 3-hr continuous
      infusion of a dilute solution compared with bolus infusion. CONCLUSIONS:
      Intestinal permeability is increased in the first 48 hrs posttrauma and decreases
      with recovery. Although one third of the patients had highly increased
      lactulose/mannitol ratios posttrauma, severity of injury, assessed by common
      scoring techniques, did not correlate with the degree of permeability. Tolerance
      to jejunal administration of lactulose and mannitol is improved with a slow
      infusion of a dilute solution over a 3-hr period compared with bolus
      administration.

PMID- 7712754
TI  - Decreased antioxidant status and increased lipid peroxidation in patients with
      septic shock and secondary organ dysfunction.
AB  - OBJECTIVE: To determine antioxidant vitamin concentrations, lipid peroxidation,
      and an index of nitric oxide production in patients in the intensive care unit
      (ICU) with septic shock and relate the findings to the presence of secondary
      organ failure. DESIGN: A prospective, observational study. SETTING: A nine-bed
      ICU in a University teaching hospital. PATIENTS: Sixteen consecutive patients
      with septic shock, defined as: a) clinical evidence of acute infection; b) hypo-
      or hyperthermia (< 35.6 degrees C or > 38.3 degrees C); c) tachypnea (> 20
      breaths/min or being mechanically ventilated); d) tachycardia (> 90 beats/min);
      e) shock (systolic pressure < 90 mm Hg) or receiving inotropes. Fourteen patients
      also had secondary organ dysfunction. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Antioxidant vitamin concentrations were significantly lower in the
      patients than the reference range obtained from a comparable group of healthy
      controls. The mean plasma retinol (vitamin A) concentration was 26.5 +/- 19.3
      micrograms/dL compared with 73.5 +/- 18.3 micrograms/dL in healthy subjects (p <
      .01). Additionally, 13 (81%) patients had retinol values below the lower limit of
      our reference range (< 37.0 micrograms/dL). Tocopherol (vitamin E) plasma
      concentrations were below the reference range in all patients (< 9.0 mg/L), with
      a mean value of 3.6 +/- 2.0 mg/L compared with 11.5 +/- 1.3 mg/L in healthy
      subjects (p < .001). Plasma beta carotene and lycopene concentrations were
      undetectable (< 15 micrograms/L) in eight (50%) patients, and below our reference
      range (< 101 micrograms/L and < 154 micrograms/L, respectively) in the remaining
      patients. In the five patients with three or more dysfunctional secondary organs,
      plasma thiobarbituric acid-reactive substances were significantly increased (p <
      .05), suggesting increased lipid peroxidation. Concentrations of thiobarbituric
      acid-reactive substances correlated negatively with both plasma retinol and
      plasma tocopherol (r2 = .42, p < .01 and r2 = .48, p < .005, respectively). In
      the five patients from whom we were able to collect urine, nitrite excretion was
      increased approximately 400-fold (p < .001). CONCLUSIONS: These data indicate
      decreased antioxidant status in the face of enhanced free radical activity, and
      suggest potential therapeutic strategies involving antioxidant repletion.

PMID- 7712756
TI  - Effects of human growth hormone in critically ill nonseptic patients: results
      from a prospective, randomized, placebo-controlled trial.
AB  - OBJECTIVES: To study the effects of growth hormone administration on insulin-like
      growth factor I concentration, nitrogen balance, and fuel utilization, and to
      study its safety in critically ill nonseptic patients. DESIGN: Prospective,
      randomized, placebo-controlled trial. SETTING: Medical intensive care unit of a
      university hospital. PATIENTS: Eighteen critically ill nonseptic patients were
      studied for 8 days after admission. INTERVENTIONS: Growth hormone (0.1 mg/kg/day)
      or placebo was administered as a continuous intravenous infusion on the second,
      third, and fourth days after admission. The study period was 8 days. MEASUREMENTS
      AND MAIN RESULTS: Plasma hormone concentrations were measured every 6 hrs and
      average daily values were calculated. The 24-hr urinary nitrogen and 3
      methylhistidine excretion were measured. Indirect calorimetry was used to
      calculate fuel utilization. Insulin-like growth factor I concentrations increased
      in the treatment group from subnormal to normal values and remained increased
      despite discontinuation of growth hormone treatment (p = .02). Nitrogen balance
      differed between the groups upon admission: growth hormone group (3.9 +/- 4.1
      g/day) vs. controls (13.8 +/- 5.4 g/day), but improved with growth hormone. This
      finding appeared independent of the imbalance between the groups. The 3
      methylhistidine excretion was not different between the groups and did not change
      during growth hormone administration. Free fatty acids and glycerol
      concentrations increased during growth hormone treatment, but calculated fuel
      utilization did not change. During growth hormone treatment, insulin
      concentrations increased, due to the increased administration of insulin
      necessary for glycemic control. Side effects other than hyperglycemia were not
      observed. CONCLUSIONS: Growth hormone administration in a heterogeneous group of
      critically ill nonseptic patients resulted in normalization of insulin-like
      growth factor I levels, even after cessation of growth hormone treatment.
      Nitrogen balance improved, but this change was transient. Hence, growth hormone
      affects nitrogen balance, probably partly independent of insulin-like growth
      factor I.

PMID- 7712757
TI  - Metabolic stress modifies the thermogenic effect of dobutamine in man.
AB  - OBJECTIVE: To study if metabolic stress modifies the thermogenic effect of
      dobutamine. DESIGN: Prospective, increasing dose, pharmacologic study. SETTING:
      Laboratory of the Department of Intensive Care Unit at a university hospital.
      SUBJECTS: Twelve normal volunteers. INTERVENTIONS: Dobutamine hydrochloride was
      infused to 12 healthy male volunteers starting at a dose of 2 micrograms/min/kg
      and gradually increased to 4 and 6 micrograms/min/kg. Each dose of dobutamine was
      infused for 20 mins. Metabolic stress was induced in six of the 12 volunteers
      using a triple hormone infusion (epinephrine, cortisol, and glucagon) before
      dobutamine, and was continued at a constant rate during the dobutamine infusion.
      The remaining six volunteers served as the control group and received only
      dobutamine. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption (VO2) was measured
      using a metabolic monitor. Arterial blood pressure was measured noninvasively,
      and cardiac output was monitored by Doppler echocardiography. Plasma
      concentrations of dopamine, norepinephrine, and epinephrine were measured in both
      groups. In the triple hormone group, blood was sampled to measure concentrations
      of insulin, glucagon, cortisol, free fatty acids, and glycerol to ensure the
      presence of a metabolic stress reaction. At the maximum dose, dobutamine induced
      a 19% increase (from 140 +/- 17 to 166 +/- 17 mL/min/m2) in VO2 in the control
      group and an 11% increase (from 167 +/- 10 to 184 +/- 13 mL/min/m2) in the triple
      hormone group (p < .05 between the two groups) compared with baseline. No change
      in the respiratory exchange ratio was seen. The triple hormone infusion alone
      induced hypermetabolism, a marked hemodynamic response, and increased lipolysis.
      CONCLUSIONS: Stress, induced by a triple hormone infusion, diminishes the
      thermogenic effect of dobutamine. In the clinical setting, a > 10% to 15%
      increase in VO2 in response to dobutamine may not be explained just by the
      thermogenic effect of the drug.

PMID- 7712758
TI  - Evaluation of the clinical usefulness of thermodilution volumetric catheters.
AB  - OBJECTIVE: To determine if treatment modalities (fluid, inotropes, and blood)
      would be altered based on preload measurements of right ventricular end-diastolic
      volume index measured by fast response thermodilution catheter, as compared with
      pulmonary artery occlusion pressure (PAOP). DESIGN: A prospective clinical trial.
      SETTING: An 11-bed surgical intensive care unit (ICU) at The Queen's Medical
      Center, an affiliate of the University of Hawaii Surgical Residency program.
      PATIENTS: Surgical ICU patients who required pulmonary artery catheters, except
      those patients with arrhythmias or history of tricuspid valve disease.
      INTERVENTIONS: During the first 48 hrs after catheter insertion, hemodynamic data
      were obtained at least every 4 hrs. Treatment of low preload was initiated only
      if clinical indications were present. These indications included a mean arterial
      pressure of < 70 mm Hg, heart rate of > 120 beats/min, urine output of < 40
      mL/hr, stroke volume of < 40 mL/m2 with oxygen delivery of < 450 mL/min/m2, and
      lactic acidosis. Volume infusion was considered if PAOP was < 18 mm Hg and right
      ventricular end-diastolic volume index was < 140 mL/m2. Treatment was given
      tohigh preload, defined as a PAOP of > 18 mm Hg to prevent pulmonary edema. When
      PAOP and right ventricular end-diastolic volume index gave conflicting
      information, other clinical parameters were assessed to determine treatment.
      MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients requiring 70 catheters were
      evaluated for the study. Thirteen patients with 46 pairs of data points completed
      the study. Fourteen patients were excluded from analysis due to irregular heart
      rate, poor quality of cardiac output at the time of volume infusion, or lack of
      major volume manipulation. PAOP and right ventricular end-diastolic volume index
      measurements agreed in 42 of 46 instances (PAOP of < 18 mm Hg, right ventricular
      end-diastolic volume index of < 140 mL/m2), leading to fluid treatment. In one
      instance, PAOP was > 18 mm Hg, right ventricular end-diastolic volume index was <
      140 mL/m2, and the patient had normal blood pressure and good urine output. PAOP
      was used in this instance as a guide to diurese the patient, which led to
      improvement of heart rate and stroke volume index. Three measurements in two
      patients with high intra-abdominal pressure indicated a PAOP of > 18 mm Hg with
      right ventricular end-diastolic volume index of < 140 mL/m2. A rigid abdomen
      accompanied hypotension, tachycardia and low urine output. Thus, a fluid bolus
      was administered, resulting in improved blood pressure, stroke volume, and heart
      rate. PAOP were obtained at end-expiration. Positive end-expiratory pressure
      (PEEP) was removed for < 1 sec, if patients were on PEEP > or = 10 cm H2O, to
      avoid the effects of high intrapleural pressure on PAOP readings. Cardiac output
      was measured at end-expiration, and stroke volume index and right ventricular end
      diastolic volume index were derived. CONCLUSIONS: In this small sample of
      surgical patients with sepsis, adult respiratory distress syndrome, and
      hemorrhagic shock (n = 13), the additional information derived from right
      ventricular end-diastolic volume index did not change treatment in 43 of 46
      instances. However, patients with increased intra-abdominal pressures may show
      misleadingly high PAOP despite low preload. These patients clearly benefitted
      from the additional information derived from ventricular volume measurements.
      Additionally, clinicians who are reluctant to take off-PEEP PAOP may also find
      this catheter useful.

PMID- 7712759
TI  - Comparison of the effect of intermittent administration and continuous infusion
      of famotidine on gastric pH in critically ill patients: results of a prospective,
      randomized, crossover study.
AB  - OBJECTIVES: To compare the effects of intermittent intravenous administration and
      continuous intravenous infusion of famotidine on gastric pH in critically ill
      patients. DESIGN: A prospective, randomized, crossover study of continuous
      infusion and bolus administration of famotidine in critically ill patients.
      SETTING: A 14-bed medical intensive care unit (ICU) of a 500-bed county hospital.
      PATIENTS: Medical ICU patients requiring stress ulcer prophylaxis. INTERVENTIONS:
      Patients were randomized to receive an equivalent dose of famotidine by
      continuous infusion or intravenous bolus for 24 hrs, and then were crossed over
      to the other arm of the study. MEASUREMENTS AND MAIN RESULTS: Critically ill
      patients who met the inclusion criteria were randomly assigned to receive
      famotidine 20 mg i.v. over 10 mins, every 12 hrs or a continuous infusion of 1.7
      mg/hr for 24 hrs. After a 16-hr washout period, patients crossed over to the
      other arm of the study. Gastric pH was monitored continuously for 24 hrs. A total
      of 710 gastric pH measurements were obtained for each phase of the study. The
      mean area under the pH-time curve for a 24-hr period was higher for continuous
      infusion than bolus administration (p = .05). Continuous infusion of famotidine
      maintained a gastric pH of > or = 4 over a longer time period than bolus
      administration (20.8 hrs vs. 12.6 hrs, respectively; p < .01). Onset of
      therapeutic gastric pH for continuous infusion was slightly delayed as compared
      with bolus administration. CONCLUSIONS: Continuous infusion of famotidine is more
      effective than an equivalent dose given by intermittent bolus in maintaining the
      appropriate gastric pH necessary for prevention of stress ulceration. Delayed
      onset of effect may warrant a priming dose when famotidine is given by continuous
      infusion.

PMID- 7712760
TI  - Effects of temperature on bleeding time and clotting time in normal male and
      female volunteers.
AB  - OBJECTIVE: This study was done to assess the effects of temperature on bleeding
      time and clotting time in normal male and female volunteers. DESIGN: Open study
      utilizing normal volunteers. SETTING: University research laboratory. SUBJECTS:
      Fifty-four healthy male and female volunteers, ranging in age from 19 to 35 yrs,
      who were not receiving medications. The study was done and the samples of venous
      blood and shed blood collected at the template bleeding time site were obtained
      at a convenient time for each volunteer. INTERVENTIONS: Skin temperature was
      changed from +20 degrees to +38 degrees C and blood samples were obtained from
      the antecubital vein of each volunteer. MEASUREMENTS AND MAIN RESULTS: The effect
      of local skin temperature ranging from +20 degrees to +38 degrees C on bleeding
      time was evaluated in 38 normal volunteers (19 male and 19 female). Skin
      temperature was maintained at +20 degrees to +38 degrees C by cooling or warming
      the forearm. At each temperature, measurements were made of complete blood count,
      bleeding time, and thromboxane B2 concentrations in shed blood collected at the
      template bleeding time site and in serum and plasma isolated from blood collected
      from the antecubital vein. Clotting time studies were measured in 16 normal
      volunteers (eight male and eight female) at temperatures ranging from +22 degrees
      to +37 degrees C. At +32 degrees C, the bleeding time was longer and hematocrit
      was lower in female than in male volunteers. However, at local skin temperatures
      of < +32 degrees C, both the males and females exhibited significantly increased
      bleeding times, which were associated with a reduction in shed blood thromboxane
      B2. Each 1 degree C decrease in temperature was associated with a 15% decrease in
      the shed blood thromboxane B2 concentration. Clotting times were three times
      longer at +22 degrees C than at +37 degrees C. Each 1 degree C reduction in the
      temperature of the clotted blood was associated with a 15% reduction in the serum
      thromboxane B2 concentration. CONCLUSION: Our data indicate that during surgical
      procedures, it is important to maintain normothermia to ensure that platelets and
      clotting proteins function optimally.

PMID- 7712761
TI  - Effects of inhibition of endothelium-derived relaxation factor on hemodynamics
      and oxygen utilization during group B streptococcal sepsis in piglets.
AB  - OBJECTIVE: To determine the effects of the inhibition of endothelium-derived
      relaxation factor in an animal model of neonatal group B streptococcal sepsis.
      DESIGN: Comparison of three experimental protocols: a) N-nitro-L-arginine; b)
      group B streptococcal; and c) group B streptococcal/N-nitro-L-arginine. SUBJECTS:
      Piglets, 1 to 2 wks old. INTERVENTIONS: Endothelium-derived relaxation factor
      inhibition was produced in nonseptic piglets by the infusion of a competitive
      inhibitor of nitric oxide synthase, N-nitro-L-arginine, at 30 mg/kg (N-nitro-L
      arginine protocol; n = 6). Human group B streptococcal sepsis was modeled in
      piglets by the continuous infusion of live group B streptococcal organisms at
      approximately 5 x 10(9) organisms/kg cumulative dose (group B streptococcal
      protocol; n = 8). Endothelium-derived relaxation factor inhibition during a group
      B streptococcal sepsis was produced by N-nitro-L-arginine infusion during
      continuing group B streptococcal infusion (group B streptococcal/N-nitro-L
      arginine protocol; n = 7). MEASUREMENTS AND MAIN RESULTS: Both N-nitro-L-arginine
      and group B streptococcal infusion significantly increased systemic and pulmonary
      vascular resistance and decreased cardiac output and oxygen delivery. N-nitro-L
      arginine differed from group B streptococcal infusions in its effects on systemic
      blood pressure (BP) (N-nitro-L-arginine increased BP while group B streptococcal
      infusions did not), and pulmonary/systemic vascular resistance ratio (group B
      streptococcal infusions increased pulmonary/systemic vascular resistance ratio
      more than N-nitro-L-arginine did). The group B streptococcal/N-nitro-L-arginine
      group differed significantly from piglets receiving continued group B
      streptococcal infusion without N-nitro-L-arginine in cardiac output
      (significantly lower in group B streptococcal/N-nitro-L-arginine), oxygen
      delivery (significantly lower in group B streptococcal/N-nitro-L-arginine), and
      pulmonary vascular resistance (significantly higher in group B streptococcal/N
      nitro-L-arginine). CONCLUSIONS: Group B streptococcal sepsis in human newborns
      and in animal models of human newborns is characterized by a hemodynamic
      constellation of "cold shock"--increased vascular resistance and reduced systemic
      blood flow. Endothelium-derived relaxation factor inhibition during group B
      streptococcal sepsis in piglets exacerbated many of the adverse hemodynamic
      consequences of group B streptococcal infusion. We speculate that endothelium
      derived relaxation factor inhibition has no foreseeable therapeutic role in
      neonatal septic shock.

PMID- 7712762
TI  - Blood flow and perfusion pressure during open-chest versus closed-chest
      cardiopulmonary resuscitation in pigs.
AB  - OBJECTIVE: To evaluate the blood flow and perfusion pressure differences observed
      during open- vs. closed-chest cardiopulmonary resuscitation (CPR), including the
      effects of epinephrine and sodium bicarbonate administration. DESIGN:
      Prospective, randomized, controlled trial. SETTING: Experimental animal
      laboratory in a university hospital. SUBJECTS: A total of 35 anesthetized
      piglets. INTERVENTIONS: After tracheostomy and insertion of arterial, right
      atrial, and pulmonary arterial catheters, thoracotomy was performed with
      placement of a pulmonary arterial flow probe and left atrial catheter.
      Ventricular fibrillation was induced and followed by 15 mins of either open-chest
      (n = 14) or closed-chest (n = 21) CPR. A 4-min infusion of 50 mmol of sodium
      bicarbonate or saline was added at the start of CPR. After 8 mins of CPR, 0.5 mg
      of epinephrine was given intravenously, and after 15 mins, direct current (DC)
      shocks were used to revert the heart to sinus rhythm. MEASUREMENTS AND MAIN
      RESULTS: Blood flow was studied using transit-time ultrasound flowmetry. In an
      extended group, intrathoracic pressure was measured for calculation of transmural
      pressure. Before epinephrine administration, mean pulmonary arterial flow
      (cardiac output) was reduced: a) during closed-chest CPR relatively more than
      pulmonary perfusion pressure but in proportion to systemic perfusion pressure; b)
      during open-chest CPR relatively less than pulmonary perfusion pressure but still
      in proportion to systemic perfusion pressure. Epinephrine administration
      temporarily increased systemic perfusion pressure during both closed- and open
      chest CPR but temporarily decreased pulmonary perfusion pressure only during
      closed-chest CPR. After epinephrine administration, cardiac output temporarily
      decreased during both closed-and open-chest CPR. CONCLUSIONS: Open-chest CPR
      resulted in better cardiac output and systemic perfusion pressure than closed
      chest CPR. However, cardiac output values obtained with both methods were much
      lower than previously reported. After epinephrine administration, cardiac output
      became extremely low with both methods.

PMID- 7712763
TI  - Effect of extracorporeal membrane oxygenation flow on pulmonary capillary blood
      flow.
AB  - OBJECTIVE: To validate a new application of the modified acetylene rebreathing
      method for pulmonary capillary blood flow in a swine extracorporeal membrane
      oxygenation (ECMO) model. DESIGN: Prospective, sequential measurements of
      pulmonary capillary blood flow, using a rebreathing technique, as affected by
      different flows through the ECMO circuit. SETTING: A cardiovascular hemodynamic
      research laboratory at a university medical center. SUBJECTS: Fifteen young
      mature farm swine (48 to 52 kg). INTERVENTIONS: Pulmonary capillary blood flow
      was measured using a modified rebreathing technique, and this measurement
      repeated at different flow rates through the extracorporeal membrane oxygenation
      circuit. Pulmonary artery flow rates were measured using both thermodilution and
      echo-Doppler techniques for comparison purposes. MEASUREMENTS AND MAIN RESULTS:
      Pulmonary capillary blood flow measurements, as assessed by modified acetylene
      rebreathing, compared well with both the thermodilution cardiac output
      measurement during normal circulation and the pulmonary artery flow probe
      measurement while the subjects received ECMO. Mean pulmonary capillary blood flow
      measured by acetylene rebreathing decreased from 89.72 +/- 6.97 (baseline) to
      43.59 +/- 5.66 mL/kg/min as ECMO flow was maximized to 56.22 +/- 3.62 mL/kg/min.
      Decreasing the ECMO flow rate by half (to 28.23 +/- 3.45 mL/kg/min) caused an
      increase in mean pulmonary capillary blood flow to 53.79 +/- 6.16 mL/kg/min. When
      ECMO flow was discontinued, pulmonary capillary blood flow returned to a near
      baseline value of 71.68 +/- 7.05 mL/kg/min (mean values of pooled data for both
      closed- and open-chest animals [n = 15]). These measurements correlated well with
      both thermodilution cardiac output and pulmonary artery ultrasonic flow probe
      measurements. CONCLUSIONS: The modified acetylene rebreathing method is a valid
      and accurate method for the measurement of pulmonary capillary blood flow in the
      presence of ECMO flows. Pulmonary blood flow decreases as ECMO flow is increased,
      and the extent of decrease is directly proportional to the amount of flow through
      the extracorporeal circulation.

PMID- 7712764
TI  - Myocardial metabolic changes during reperfusion of ventricular fibrillation: a
      31P nuclear magnetic resonance study in swine.
AB  - OBJECTIVE: Myocardial metabolic requirements during reperfusion of ventricular
      fibrillation are poorly understood. The objective of this study was to determine
      if controlled reperfusion after a clinically relevant global ischemia period of
      10 mins was sufficient to prevent or reverse myocardial ischemia as indicated by
      changes in myocardial high energy phosphates, myocardial intracellular pH, and
      great cardiac vein lactate. DESIGN: Prospective laboratory study with controlled
      reperfusion. SETTING: Research laboratory at a university medical center.
      SUBJECTS: Five swine weighing 19 +/- 3 kg. INTERVENTIONS: Ten minutes of
      nonperfused ventricular fibrillation followed by reperfusion with cardiopulmonary
      bypass (flow 30 mL/kg/min) for 50 mins. MEASUREMENTS AND MAIN RESULTS: Myocardial
      adenosine triphosphate (ATP), phosphocreatine, and intracellular pH were
      determined using in vivo 31P nuclear magnetic resonance. Myocardial blood flow,
      measured by 15-mu radiolabeled microspheres, was significantly increased above
      baseline during reperfusion. Phosphocreatine was depleted during the 10 mins of
      nonperfused ventricular fibrillation, but recovered to 122 +/- 18% of baseline
      with reperfusion and was 112 +/- 18% at 60 mins (p < .005). ATP concentrations
      decreased to 51 +/- 16% of baseline after 10 mins of nonperfused ventricular
      fibrillation, improved to 67 +/- 9% of baseline with early reperfusion, and were
      65 +/- 9% of baseline at 60 mins (p < .02). Myocardial intracellular pH improved
      from 6.11 +/- 0.18 after 10 mins of nonperfused ventricular fibrillation, to 6.89
      +/- 0.20 with early reperfusion, and then decreased to 6.85 +/- 0.35 at 60 mins
      ventricular fibrillation (p < .001). Despite myocardial blood flows higher than
      baseline during the reperfusion period, great cardiac vein/aortic lactate
      gradient increased over the reperfusion period. CONCLUSION: Prolonged reperfusion
      with supranormal myocardial blood flow does not restore normal myocardial aerobic
      metabolism in the fibrillating myocardium after a 10-min nonperfused ventricular
      fibrillation period.

PMID- 7712765
TI  - A blind, randomized comparison of the circulatory effects of dopamine and
      epinephrine infusions in the newborn piglet during normoxia and hypoxia.
AB  - OBJECTIVE: To determine the hemodynamic responses to dopamine and epinephrine
      infusions in newborn piglets during normoxia and hypoxia. DESIGN: Prospective,
      randomized, blind cross-over study. SUBJECTS: Newborn piglets (n = 7).
      INTERVENTIONS: Animals were acutely instrumented for measurements of cardiac
      output, pulmonary and systemic pressures, carotid and coronary artery blood flow,
      and coronary artery oxygen consumption. Dopamine at infusion rates of 2 to 16
      micrograms/kg/min and epinephrine 0.2 to 1.6 micrograms/kg/min were administered
      during normoxia. Six piglets were similarly prepared and were then made hypoxic
      to an arterial O2 saturation of 45% to 50%. Epinephrine at infusion rates of 0.2
      to 3.2 micrograms/kg/min and dopamine at rates of 2 to 32 micrograms/kg/min were
      administered in random order during hypoxia. MEASUREMENTS AND MAIN RESULTS:
      During normoxia, cardiac output increased similarly with both drugs and was
      significantly increased by > or = 0.2 micrograms/kg/min of epinephrine and
      significantly increased by 8 or 16 micrograms/kg/min of dopamine. Mean arterial
      blood pressure was not affected by dopamine but was significantly increased by
      epinephrine at a rate of 1.6 micrograms/kg/min. The relative effects of the drugs
      on pulmonary and systemic vascular resistance differed, the pulmonary/systemic
      vascular resistance ratio was reduced at the higher doses of epinephrine (i.e.,
      0.8 and 1.6 micrograms/kg/min) and was unaffected by dopamine. Coronary artery
      oxygen consumption and coronary blood flow increased significantly with both
      medications at rates > 0.4 and 4 micrograms/kg/min, respectively. Increases of
      both variables were greater with epinephrine than with dopamine. Myocardial
      extraction ratio was unaffected by dopamine and reduced at 0.2 and 1.6
      micrograms/kg/min of epinephrine. Hypoxia caused significant increases in cardiac
      index, systemic blood pressure, pulmonary arterial pressure, carotid artery blood
      flow, coronary artery blood flow, coronary oxygen consumption, coronary oxygen
      extraction ratio, and the pulmonary/systemic vascular resistance ratio. Mean
      systemic arterial blood pressure increased significantly with 1.6 and 3.2
      micrograms/kg/min of epinephrine, but was not significantly affected by dopamine
      at any infusion rate. Cardiac index was not affected significantly by either of
      the medications. Thus, there was a significant increase in the calculated
      systemic vascular resistance index with the highest dose of epinephrine, in
      contrast to the slight, statistically significant, decrease in calculated
      systemic vascular resistance index with the highest dose of dopamine. Epinephrine
      significantly reduced pulmonary arterial pressures at 0.2, 0.4, and 0.8
      microgram/kg/min. Dopamine had no effect on this variable. The pulmonary/systemic
      vascular resistance ratio was significantly reduced by epinephrine at doses of
      0.2 and 3.2 micrograms/kg/min, whereas the highest dose of dopamine caused a
      significant increase in the pulmonary/systemic vascular resistance ratio.
      CONCLUSIONS: Epinephrine infusion during normoxia increases systemic pressure
      more than pulmonary arterial pressure at doses > or = 8 micrograms/kg/min, and
      furthermore, produces a more appropriate hemodynamic profile in the presence of
      hypoxic pulmonary hypertension than dopamine infusion, in the acutely operated
      anesthetized piglet.

PMID- 7712766
TI  - Contribution of airway hyperresponsiveness to lower airway obstruction after
      extracorporeal membrane oxygenation for meconium aspiration syndrome.
AB  - OBJECTIVE: To determine whether airway hyperresponsiveness contributes to the
      development of lower airway obstruction in infants recovering from severe
      meconium aspiration syndrome treated with extracorporeal membrane oxygenation
      (ECMO). DESIGN: Prospective comparison study of the response to bronchodilator
      during the acute and convalescent phase of severe meconium aspiration. SETTING:
      Pediatric/neonatal intensive care unit in a tertiary care hospital. PATIENTS:
      Seven neonates with severe meconium aspiration syndrome that was refractory to
      conventional mechanical ventilation, requiring ECMO treatment. INTERVENTIONS:
      Evaluation of the effect of bronchodilator treatment on the airway function at a
      postnatal age of 14 +/- 2.7 (SEM) days, after the patients had been off ECMO for
      4.6 +/- 1.4 days, and comparison with the response the same patients had shown at
      a postnatal age of 2.7 +/- 0.6 days, when they had been on ECMO for 1.3 +/- 0.6
      days. Lung mechanics and lower airway function were measured and compared before
      and after administration of aerosolized isoetharine early in the course of ECMO
      and again several days after ECMO. Maximum expiratory flow-volume curves produced
      by the deflation flow-volume curve technique were used for evaluating the lower
      airway function, and partial passive flow-volume curves were used for measuring
      respiratory system compliance and resistance. MEASUREMENTS AND MAIN RESULTS:
      During the first test, isoetharine produced a mild increase in maximum expiratory
      flows at 25% (MEF25) of forced vital capacity (FVC) (48 +/- 27% compared with
      baseline values), without significant change in the MEF25 to FVC ratio. During
      the second test approximately 2 wks later (post-ECMO), isoetharine increased
      MEF25 by 123 +/- 29% and increased the MEF25/FVC by 40 +/- 13% compared with
      baseline values. The percent change in both indices was significantly higher
      during the second test (p < .05) than in the first test. CONCLUSIONS: Airway
      obstruction in infants recovering from severe meconium aspiration syndrome is
      partially reversible with aerosolized isoetharine, indicating that airway
      hyperresponsiveness contributes to the pathogenesis of airway obstruction.

PMID- 7712767
TI  - Acute hypoxemic respiratory failure in children following bone marrow
      transplantation: an outcome and pathologic study.
AB  - OBJECTIVES: To describe the pulmonary pathology and clinical outcome in children
      with acute hypoxemic respiratory failure after bone marrow transplantation.
      DESIGN: Review of medical records and pathologic material of patients diagnosed
      with acute hypoxemic respiratory failure after bone marrow transplantation.
      SETTING: Pediatric intensive care unit (ICU) of a teaching hospital. PATIENTS AND
      METHODS: Retrospective review of a consecutive cohort of children, with a history
      of bone marrow transplantation admitted to the pediatric ICU during a 7-yr study
      period, and who met a published definition of acute hypoxemic respiratory
      failure. For each admission, the pediatric ICU course and outcome were reviewed.
      Pathologic material that was obtained from the patients was reexamined and
      assigned to one of the following categories: acute or organizing diffuse alveolar
      damage, pulmonary hemorrhage, nonspecific interstitial pneumonitis, or infectious
      pneumonia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-three
      patients satisfied criteria for inclusion in the study group. Indications for
      bone marrow transplantation were: solid tumor (30%), leukemia (44%), congenital
      immunodeficiency (19%), and aplastic anemia (7%). Patients were admitted to the
      pediatric ICU a median of 1 month (range 0 to 126) after bone marrow
      transplantation. Thirty-eight (88%) patients died in the pediatric ICU. Tissue
      histologic material was available from 21 (49%) patients. Six (29%) of 21
      patients had acute diffuse alveolar damage; one (5%) had organizing diffuse
      alveolar damage; three (14%) had nonspecific interstitial pneumonitis; and two
      (10%) had pulmonary hemorrhage. Infectious pneumonia occurred in nine (43%) cases
      (five fungal; four viral). CONCLUSIONS: The acute mortality rate (88%) for
      children with acute hypoxemic respiratory failure after bone marrow
      transplantation is similar to that reported for adults with this combination of
      conditions. Diffuse alveolar damage, the histologic hallmark of adult respiratory
      distress syndrome, was present in a minority (33%) of patients. Infectious
      pneumonia was the most frequent cause of acute hypoxemic respiratory failure in
      patients who had pathologic tissue available, emphasizing the need for aggressive
      diagnostic studies and early institution of antifungal and antiviral therapy.

PMID- 7712769
TI  - Pediatric critical care physicians' attitudes about guidelines for the use of
      ribavirin in critically ill children with respiratory syncytial virus pneumonia.
AB  - OBJECTIVE: To determine the attitude of pediatric critical care physicians
      concerning the use of ribavirin in children with respiratory syncytial virus lung
      disease in light of the revised American Academy of Pediatrics practice
      guidelines. DESIGN: A questionnaire was sent to 145 pediatric critical care
      doctors in the United States. MEASUREMENTS AND MAIN RESULTS: Seventy-seven
      percent of questionnaires were returned. The vast majority (91%) of the
      respondents think that the available literature does not support the Academy's
      recommendations for the administration of ribavirin to critically ill children
      with respiratory syncytial virus pneumonia. The largest single group of
      respondents (42%) does not usually prescribe ribavirin for these patients, but
      may be persuaded to use it by colleagues or consultants in individual cases.
      Twenty-six percent of all respondents stated that they do not use ribavirin at
      any time, even in severely ill patients with documented infection. Twenty-two
      percent of the respondents say that they will prescribe ribavirin, not because
      they believe it is efficacious, but because they believe the Academy guidelines
      compel them to do so as a standard of care. The respondents reported adverse
      effects of the drug, most notably exacerbations of bronchospasm (92%), far more
      often than the Academy document asserts. When solicited for general comments, the
      respondents were frequently concerned that critical care physicians were not
      involved in the development of the guidelines, the guidelines were based on a
      paucity of reliable data, and that the guidelines could put them at risk of
      malpractice litigation should they choose to not use ribavirin. CONCLUSIONS:
      Practice guidelines are increasingly being incorporated into patient care and
      quality improvement regimens, and it is imperative both that appropriate experts
      be included in their development, and that they be based on valid scientific
      data. The pediatric critical care community currently treats most of the severely
      ill patients with respiratory syncytial virus pneumonia. As a group, they remain
      unconvinced about the efficacy and safety of this drug, and many pediatricians
      are concerned about the ramifications of individualizing ribavirin therapy in
      their patients in light of the revised Academy recommendations.

PMID- 7712771
TI  - Fatal adult respiratory distress syndrome after diphenhydramine toxicity in a
      child: a case report.

PMID- 7712770
TI  - Intra-abdominal hemorrhage complicating hypertensive therapy for cerebral
      vasospasm.

PMID- 7712768
TI  - Physicians do not have a responsibility to provide futile or unreasonable care if
      a patient or family insists.
AB  - OBJECTIVE: This article was written to argue that physicians are not ethically
      obligated to provide care which they consider futile, unreasonable, or both,
      either voluntarily or in response to patient or surrogate demands. DATA SOURCES:
      Data used to prepare this article were drawn from published articles, including
      original investigations, position papers and editorials in the author's personal
      files. STUDY SELECTION: Articles were selected for their relevance to the
      subjects of medical ethics, the concepts of futility and medical reasonableness,
      case law, and healthcare reform. DATA EXTRACTION: The author extracted all
      applicable data. DATA SYNTHESIS: Physicians may feel obligated to provide care in
      all clinical circumstances due to the single master view of medicine and the
      ethical principle of autonomy. However, care may be considered futile according
      to several definitions of that word, including that which describes futile
      treatment as something that does not benefit the patient as a whole. Furthermore,
      care may be considered unreasonable if it is excessive and not generally agreed
      upon. Physician refusal to provide futile or unreasonable care is supported by
      the ethical principles of nonmaleficence, beneficence, and distributive justice.
      The last principle is particularly relevant in the current climate of healthcare
      reform. CONCLUSIONS: Although the issue of physician refusal of requested care
      has not been resolved by case law or legal statute, it is supported by compelling
      ethical principles. Physicians are not ethically required to provide futile or
      unreasonable care, especially to patients who are brain dead, vegetative,
      critically or terminally ill with little chance of recovery, and unlikely to
      benefit from cardiopulmonary resuscitation.

PMID- 7712772
TI  - Ketoconazole for prophylaxis of the adult respiratory distress syndrome.

PMID- 7712773
TI  - Gram-negative pulmonary colonization in liver transplant patients.

PMID- 7712774
TI  - Perfluorochemical emulsion for resuscitation of experimental hemorrhagic shock.

PMID- 7712775
TI  - Aerosolized ribavirin in mechanically ventilated children with respiratory
      syncytial virus lower respiratory tract disease.

PMID- 7712776
TI  - Continuous intra-arterial blood gas monitoring.

PMID- 7712777
TI  - Neurologic dysfunction after isoflurane sedation.

PMID- 7712778
TI  - Tlaxcalan constructions of acute grief.
AB  - In rural Tlaxcala, Mexico, the sudden and unexpected death of infants and young
      children was a relatively common occurrence during the time when this study was
      conducted. Not surprisingly, the deaths constituted major social tragedies and
      operated as psychological traumas to the family, especially the parents. Acute
      grief reactions inevitably resulted and these were suffused with bodily and
      psychological disturbances of different types, some of which were handled in the
      society as illness. The article grows out of a longitudinal study about these
      tragedies to families of the region. Attention is given to the grief reactions of
      parents, with special emphasis placed on psychological and behavioral
      manifestations. Of particular interest is the way local, cultural symbols
      pertaining to the cause of the deaths, which involved the malevolent attack of
      blood-sucking witches, were configured in the verbalizations and behavioral
      reactions that comprised the grief reactions. Details of the way symbols entered
      into the construction of meaningful accounts of the tragedies during the ordeal
      of the grief reactions are discussed and analyzed. Although the manifestations of
      grief could be said to have clinical, psychiatric implications, it is the way
      these manifestations served to explain the tragedies, in the process regulating
      and restoring social relations, that is given principal attention. A description
      of one mother's grief reaction is provided as a case illustration.

PMID- 7712780
TI  - Rhythm in Chinese thinking: a short question for a long tradition.
AB  - This paper tries to shed a fresh light on the use of several key terms in
      traditional Chinese medicine (and philosophy) related to the theory of so-called
      systematic correspondence. Drawing on some influential works in Chinese science
      and civilization (e.g., Marcel Granet, Joseph Needham, Nathan Sivin), the paper
      argues that the idea of rhythm, properly defined, should become an organizing
      idea in studying the traditions of Chinese thinking and practice in medicine as
      well as in general. Rhythmicity is not periodicity (though they are inseparable
      from one another) and the idea of rhythm is more useful (than for example the
      notion of correspondence) for medical anthropology. The paper is divided into
      three parts: 1) the idea of rhythm in some key terms of traditional Chinese
      medicine, 2) the Chinese theory of resonance versus the idea of rhythm, and 3)
      the relation of resonance, rhythm and ecstatic experiences with respect to
      medical anthropology. An acquaintance with the arguments of my previous article
      in these pages will be helpful but not necessary for the present paper.

PMID- 7712779
TI  - Female sexuality, social reproduction, and the politics of medical intervention
      in Niger: Kel Ewey Tuareg perspectives.
AB  - This essay explores connections between political institutions, forms of power,
      and women's health care concerns from a cultural anthropological perspective. I
      focus on the roles of different medical establishments among the Kel Ewey Tuareg
      of Niger--Western-European sponsored, central state, traditional herbalism and
      Islamic scholarship--in creating, maintaining, and disputing these constructs,
      through the invention and elaboration of disease categories and through the
      selective application of medical and reproductive models and technology to women.
      I also explore women's attempts to manage these forces, as they draw upon a
      cultural inventory that is alternately supportive and in conflict with their
      interests.

PMID- 7712781
TI  - Professor. Interview by Saundra Woodruff.

PMID- 7712782
TI  - ICUs.

PMID- 7712784
TI  - Research. Interview by Saundra Woodruff.

PMID- 7712786
TI  - Health fairs.

PMID- 7712783
TI  - A day in the life.

PMID- 7712787
TI  - Scholarships.

PMID- 7712785
TI  - Critical Distance Walk and Run.

PMID- 7712788
TI  - 25-year member. Interview by Shannon Spear.

PMID- 7712789
TI  - Ethics. Interview by Bonnie Horrigan.

PMID- 7712791
TI  - The next step--patient-driven technology.

PMID- 7712790
TI  - Giving voice to the vision--achieving the patient-driven system.

PMID- 7712792
TI  - Using the vision to guide use of UAPs: an interview with Wanda Johanson.

PMID- 7712793
TI  - Inside the patient-driven system.

PMID- 7712794
TI  - Critical pathways: good idea, right reason?

PMID- 7712795
TI  - What journal editors would like from reviewers.

PMID- 7712796
TI  - Can high-dose methylprednisolone be diluted?

PMID- 7712797
TI  - Tissue plasminogen activator: the nurse's role.

PMID- 7712799
TI  - Pharmacologic stress testing: an alternative to exercise.

PMID- 7712800
TI  - Interleukin-2 therapy: needs of the patient in a critical care setting.
AB  - IL-2 is a biotherapeutic drug and a biological response modifier. This drug has
      not been approved by the Food and Drug Administration for general use but
      continues to undergo clinical trials. Candidates for this therapy are patients
      with advanced carcinoma that has not responded to standard modalities of
      treatment. Administration of IL-2 can lead to systemic toxicity, which usually
      appears to be dose-related. As a result, high-dose therapy requires intensive
      care. The critical care nurse assesses and documents side effects that occur as a
      result of IL-2 therapy and must be aware of both the physical and psychological
      needs of the patient. Through successful assessment and intervention, the nurse
      can gain the knowledge required to manage, both physically and psychologically,
      patients who are undergoing this therapy.

PMID- 7712798
TI  - The COPD patient in acute respiratory failure.

PMID- 7712801
TI  - Surfactant replacement in adults and children with ARDS--an effective therapy?

PMID- 7712802
TI  - Sabbatical leave: a creative retention strategy.

PMID- 7712804
TI  - Neuroleptic malignant syndrome: critical factors.
AB  - Although NMS is a rare complication of neuroleptic drug use, it is potentially
      fatal. Nursing care is directed at careful assessment, accurate treatment, and
      reduction of complications. Further studies should focus on prevention and
      treatment.

PMID- 7712803
TI  - Evaluating quantitative research designs: Part 2.

PMID- 7712805
TI  - The ethics of cadaver experimentation.

PMID- 7712806
TI  - What, if anything, does your unit do to reduce noise levels in the ICU?

PMID- 7712808
TI  - Being there.

PMID- 7712807
TI  - The patient-driven system.

PMID- 7712809
TI  - Comments on epidural analgesia article.

PMID- 7712811
TI  - Nurses in pain study need to be educated.

PMID- 7712810
TI  - "Epidural analgesia for effective pain control".

PMID- 7712813
TI  - The RN's role in manipulation of pulmonary artery catheters.
AB  - Based on three surveys of critical care nursing practice around the United
      States, practice and opinion regarding the nurse's role in PA catheter
      manipulation is clearly varied. If it is determined that a change in practice is
      indicated, the scope of practice must be examined. The potential for risk to
      patients and a facility's cultural and political barriers require discussion and
      resolution. Policy guidelines, educational programming to teach the skills
      involved, and plans for competency verification are necessary. Our intention is
      not specifically to promote nurse manipulation of PA catheters. However, because
      some RNs perform this task, we advocate approved guidelines and adequate
      training.

PMID- 7712812
TI  - Right ventricular myocardial infarction: detection, treatment, and nursing
      implications.
AB  - Conventional therapy for left ventricular infarction may potentiate hemodynamic
      instability in a patient with right ventricular MI. The nursing role includes
      screening for ECG changes, intense hemodynamic monitoring, and ensuring
      implementation of appropriate therapy.

PMID- 7712814
TI  - Measurement error in counting heart rate: potential sources and solutions.

PMID- 7712815
TI  - Third generation pacemaker-cardioverter-defibrillator: a case study.

PMID- 7712816
TI  - Comfort issues in patients undergoing radiofrequency catheter ablation.
AB  - The introduction of RFCA of accessory pathways offers an invasive yet safe cure
      for the potentially lethal arrhythmias associated with reentrant SVT. This
      lengthy procedure challenges nurses in providing patient comfort. It cannot be
      overemphasized how much these seemingly simple comfort measures can humanize an
      otherwise frighteningly "high-tech" atmosphere. Physical comfort as well as
      psychological well being will be enhanced with "high-touch" care. As RFCA becomes
      more common, further research must be directed toward maximizing comfort and
      minimizing complications.

PMID- 7712817
TI  - A new device for control of bleeding after transfemoral catheterization.

PMID- 7712818
TI  - A day late.

PMID- 7712819
TI  - Cardiac arrest during pregnancy: maternal-fetal physiology and advanced cardiac
      life support for the obstetric patient.
AB  - Although cardiac arrest in pregnancy is rare, all members of the healthcare team
      who care for pregnant women should be aware of the maternal adaptations of
      pregnancy. Also, more women with preexisting medical conditions are attempting
      pregnancy. Perinatal nurses, especially those practicing in level III (high-risk)
      perinatal centers should be trained in dysrhythmia recognition and ACLS
      protocols. Rapid intervention sometimes can save two lives.

PMID- 7712820
TI  - Use of ventricular stroke work index and ventricular function curves in assessing
      myocardial contractility.
AB  - Cardiac output and cardiac index values are traditionally used by critical care
      nurses as indicators of myocardial contractility. Due to the incidence of
      compensatory tachycardia in many critically ill patients, however, the value of
      LVSWI as an indicator of myocardial contractility is enhanced, because the
      formula for its calculation does not emphasize the variable of heart rate. The
      advantages of using LVSWI are the following: It is easily calculated at the
      bedside by using an integrated hemodynamic software package or by using the
      formula provided. It is readily available to the nurse and indicates sensitive
      changes in myocardial function. When used in LV function curves in the nursing
      assessment of myocardial contractility of critically ill adults, its use can
      direct changes in fluid and pharmacologic interventions. Factors that affect
      ventricular end-diastolic pressure such as altered myocardial compliance or
      increased transmural pressure alters PCWP. Although LVSWI is not completely
      independent of these factors and may be less precise with altered PCWP, the LVSWI
      does enhance the data base used to manage patients with altered ventricular
      function. Ideal LVSWI values may not be achievable in patients with poor
      myocardial contractility; however, tracking the LVSWI provides sensitive and
      immediate feedback on the efficacy of pharmacologic intervention. Critical care
      nurses should use the LVSWI for any hemodynamically unstable patient whose
      myocardial contractility might be compromised. This information allows the nurse
      to optimize the patient's hemodynamic performance with a more accurate assessment
      of heart function.

PMID- 7712821
TI  - Cross-training across acuity levels.

PMID- 7712823
TI  - The patient-driven system.

PMID- 7712822
TI  - ICU--from the patient's point of view. Interview by Michael Villaire.

PMID- 7712825
TI  - Cosmetic dermatitis in childhood.

PMID- 7712826
TI  - A dermatologic diary. Portrait of a practice.

PMID- 7712824
TI  - Prehospital treatment of myocardial infarction.

PMID- 7712828
TI  - Natural history of squamous cell carcinoma of the skin: case report.
AB  - Squamous cell carcinoma is a malignant proliferation of the epidermal
      keratinocyte. With early recognition and treatment, most of these tumors have a
      favorable prognosis. If the lesions are left untreated, however, the results may
      prove fatal. We describe a case of long-standing neglect of cutaneous squamous
      cell carcinoma leading to widely metastatic disease in a 69-year-old man.

PMID- 7712827
TI  - Tinea capitis.

PMID- 7712831
TI  - "Flies in the flesh": a case report and review of cutaneous myiasis.
AB  - Cutaneous myiasis is the infestation of tissue by the larvae of flies. There are
      many causes and they are geographically dependent. The clinical presentation is
      variable depending on the cause and the body part(s) affected, which can include
      skin, nasal, ocular, oral, aural, gastrointestinal, and genitourinary tracts.
      Treatment is complete removal of the larvae from the affected site. The ultimate
      goal is prevention. We briefly review a case report and then review definition,
      causes, clinical presentation, differential diagnosis, treatment, and prevention.
      Cutaneous myiasis reiterates the basics of clinical medicine, which require one
      to obtain a thorough history, including travel, potential risk exposure, and
      occupation, and to perform a complete physical examination of a patient with any
      suspicious lesion.

PMID- 7712829
TI  - Colorectal cancer presenting with a cutaneous metastatic lesion on the scalp.
AB  - Cutaneous metastases occur rarely with colorectal adenocarcinoma, accounting for
      approximately 5 percent of all cutaneous metastases. Cutaneous metastases from
      colonic cancer are most often located on the abdominal skin. The case we describe
      here is unusual because colorectal adenocarcinoma rarely metastasizes to the
      scalp. A review of the English language literature revealed only six reported
      cases of cutaneous metastases from a colonic adenocarcinoma to the scalp.

PMID- 7712830
TI  - Desmoplastic melanoma (or is it merely cicatrix?) arising at the site of biopsy
      within a conventional melanoma: pitfalls in the diagnosis desmoplastic melanoma.
AB  - We describe a case in which a "punch biopsy" specimen of a conventional melanoma
      on the cheek of a 25-year-old man led to a problem in differentiating a
      desmoplastic malignant melanoma from cicatrix. The circumstances of this case
      raise the issue of whether desmoplastic melanoma can arise at the site of trauma
      within a pre-existing melanoma.

PMID- 7712832
TI  - Relationship of LDLR gene polymorphism and NIDDM in Chinese.
AB  - Genomic DNA was extracted from peripheral blood lymphocytes of 105 healthy and 75
      NIDDM Chinese subjects. The fragment located in exon 13 of the low density
      lipoprotein receptor (LDLR) gene was amplified by polymerase chain reaction
      (PCR), and digested with restriction enzyme HincII. LDL, TC and TG levels were
      measured in all subjects. Investigations were conducted to explore the
      correlation between the HincII RFLP of LDLR gene and NIDDM in the Chinese
      population. The results showed that no significant correlation existed between
      this RFLP locus and NIDDM. Marked differences were found, however, between the
      genotype distribution of low LDL level subgroups of NIDDM patients and normal
      controls. It was inferred that the H1 allele might be associated with high blood
      cholesterol levels, and the H2 allele with low cholesterol levels. Disturbances
      of lipid metabolism occur frequently in diabetes mellitus. This study suggested
      that differences in LDLR genotypes may affect the phenotypes of lipid metabolism.

PMID- 7712833
TI  - The truss structure of cancellous bone. Morphological basis of the function of
      load transmission of the synovial joint.
AB  - The structure of cancellous bone of synovial joints was studied under the
      scanning electron microscope in 4 young cadavers. It was discovered that in all
      specimens, the cancellous bone beneath the whole coverage of the articular
      cartilage had a honeycomb pattern in appearance formed by many arched trabeculae
      running in different directions, and that the major orientation of the arched
      trabeculae was toward the articular surface. The arms of one arched trabecula
      extended in different directions, forming the tops of other arched trabeculae;
      the direction of the collagen fibers conformed circumferentially with that of the
      arch, but the collagen fibers at the intermediate part of the common arm of the
      adjacent arched trabeculae crossed in a woven pattern, passing from one trabecula
      to another. It enables the whole end of the articular bone to have the capacity
      of integral deformation. That is the foundation of the character of compliance
      which is essential to the contact of the articular surfaces changing from
      incongrouity to total congrouity during normal load transmission. This special
      type of construction is just like the truss structure in the architectural
      engineering, and therefore the authors suggest to name it the "Truss Structure"
      of the cancellous bone. The relationship between integral deformation and the
      following two factors, compliance and incongrouity of the articular surface
      provides an explanation that the truss structure of the cancellous bone is the
      morphological basis of high load-bearing capacity and character of compliance of
      the synovial joint.

PMID- 7712834
TI  - Effect of warm ischemic injury on morphology and viability of aortic valves in
      rats.
AB  - Warm ischemia is one of the most important causes of valvular damage from death
      of donor to its valve harvesting. This study aimed at using qualitative and
      quantitative methods to characterize warm ischemic injury through models of SD
      rat's aortic valves and design to show the relationship among ultrastructural,
      biological and biochemical changes concerning with the length of warm ischemia
      time (WIT). 102 harvested SD rat's aortic valves were divided into 6 groups of
      different ischemic time for this study. 432 photomicrographs of transmission
      electron microscopy (TEM) were put into computer for analysis. The volume ratio
      of nucleus to plasma in cells (Vnp) and the ratio of extramembrane area to volume
      of mitochondria (S/V) were used to characterize the degree of valvular cell
      injuries. Valvular cells culture and biochemical metabolism including glucose
      degradation and 3H-TdR absorption rate were adopted. The valvular cells depicted
      a significant decrease and 3H-TdR taking-up also being inhibited under the
      influence of prolonged WIT.

PMID- 7712835
TI  - Increased vulnerability of hypertrophied myocardium to ischemia and reperfusion
      injury. Relation to cardiac renin-angiotensin system.
AB  - Hearts of pressure-overload hypertrophy show an increased activation of
      intracardiac renin-angiotensin system which may contribute to ischemia and
      reperfusion injury. The purpose of this study is to evaluate whether the
      hypertrophied myocardium is more vulnerable to ischemia and reperfusion injury
      and to find out its relation to the cardiac renin-angiotensin system.
      Hypertrophied rat hearts induced by abdominal aortic banding for 6 weeks were
      subjected to 2 hours of hypothermic ischemic arrest followed by 30 minutes of
      reperfusion, and their cardiac function recovery was compared with that of sham
      operated normal control hearts. The cardiac renin activity and angiotensin II
      content before ischemia and after reperfusion were determined. It was found that
      both the pre-ischemic renin activity and angiotensin II level were higher in
      hypertrophied myocardium than those in the control: ischemia and reperfusion
      injury increased both renin activity and angiotensin II content in the two
      groups, but the renin activity and angiotensin II level were further elevated
      after reperfusion in the hypertrophied hearts than those in the control hearts.
      Meanwhile, the cardiac function recovery after 30 minutes reperfusion in the
      hypertrophied hearts was poorer than that in the control. Correlation analysis
      revealed that there was a negative correlation between the cardiac output
      recovery and the myocardial angiotensin II content (r = -0.8411, P < 0.001). It
      is concluded that ischemia and reperfusion injury can activate cardiac renin
      angiotensin system in isolated rat heart, which may be responsible for the
      increased susceptibility of the hypertrophied myocardium to ischemia and
      reperfusion injury.

PMID- 7712836
TI  - Experimental study on antiatherosclerotic treatment by PGE2 combined with vitamin
      E and estradiol.
AB  - The effects of single dose of PGE2 combined with vitamin E and with estradiol on
      experimental atherosclerosis were studied by means of morphological,
      ultrastructural, autoradiographic and several functional techniques. The results
      showed that two combined treatment groups had more coordinative inhibition on
      aortic and coronary atherosclerotic lesions, as well as on platelet aggregation,
      smooth muscle cell proliferation and lipid peroxidation than that of single dose
      of PGE2. It was revealed that the coordinative mechanism might be closely related
      to the synergistic inhibitory function of above-mentioned drugs on endothelial
      permeability, platelet aggregation, smooth muscle cell proliferation and lipid
      peroxidation.

PMID- 7712837
TI  - Labeling and quantitative analysis of six lectin receptors of intracranial
      gliomas.
AB  - The distribution of six lectin receptors, WGA, RCA-1, LCA, PSA, PNA and SBA in
      111 human gliomas, 8 human normal brain tissues and 11 reactive hyperplasia of
      astrocytes was observed by means of avidin-biotin-peroxidase technique. Their
      grays were also quantified with the image analysis instrument. The results showed
      that WGA and RCA-1 might be used as markers for distinguishing well
      differentiated astrocytomas from the reactive hyperplasia of astrocytes
      especially the reactivity of astrocytes had a specific feature with RCA-1. The
      difference in quantities of WGA, RCA-1, LCA, PSA receptors between astrocytomas,
      ependymomas and oligodendrogliomas, medulloblastomas might conduce to the
      diagnosis and classification. For astrocytomas, it was also showed that a
      quantity of LCA and PSA receptors was correlated with the degree of cell
      differentiation. Therefore, they can be used as valuable markers of the
      differentiation of astrocytomas.

PMID- 7712838
TI  - Encircling suture method in the treatment of femoral venous valvular
      incompetency.
AB  - Many patients with chronic venous insufficiency syndrome caused by the "relative
      valvular incompetency" with venous dilatation. Eighty-six per cent of the cases
      can be cured by reducing the femoral venous diameter by simply using the
      encircling suture method just distal to the first femoral valvular sinus. Our
      preliminary results suggest that such a method of surgical treatment is simple
      and efficient.

PMID- 7712839
TI  - Laryngotracheal flap for reconstruction of hypopharynx and upper esophagus after
      resection of advanced pyriform sinus cancer.
AB  - Reconstruction of the hypopharynx and upper esophagus after resection of advanced
      pyriform sinus cancer, is usually complicated and time-consuming. Laryngotracheal
      flap was used in hypopharyngoesophageal reconstruction for 26 elderly patients
      with advanced pyriform sinus cancer Pharyngocutaneous fistula developed in 5
      patients and healed spontaneously without further surgery. Full diet was resumed
      in all the patients. The surgical technique and its advantages and disadvantages
      are discussed. The laryngotracheal flap in the reconstruction of
      hypopharyngoesophageal defect for elderly patients is a procedure of choice.

PMID- 7712840
TI  - The population association of glucokinase gene with type 2 (noninsulin-dependent)
      diabetes mellitus in Chinese.
AB  - The association of gluckinase (GCK) gene with type 2 (non-insulin-dependent)
      diabetes mellitus was investigated in 168 Chinese subjects (85 unrelated type 2
      diabetics and 83 non-diabetic controls). The microsatellite polymorphism marker,
      GCK-5', was amplified with polymerase chain reaction. Four alleles were observed
      in Chinese population with length varying from 137bp to 143bp and the most common
      one being the 139bp allele 3. In comparison with non-diabetics, allele 4 was
      significantly increased in type 2 diabetes (10% versus 38, respectively; X2 =
      6.773, P = 0.009); genotype 44 and 4X (X denotes any allele other than allele 4)
      were significantly increased in type 2 diabetes (16% versus 6% respectively; X2 =
      6.439, P = 0.011). The frequency difference was also shown in overweight/obese
      subgroup comparison (X2 = 7.718, P = 0.021), but not in lean/normal-weight
      subgroup comparison. No differences of age of onset and frequency of positive
      family history were observed between type 2 diabetic patients with genotype 44 or
      4X and those with XX. The risk for type 2 diabetes in Chinese with genotype 44 or
      4X was about 3.5 times higher than in Chinese with genotype XX. Therefore, GCK
      gene was associated with Chinese type 2 diabetes.

PMID- 7712841
TI  - A new structure of small intensely fluorescent cells in superior mesenteric
      ganglion of human fetus.
AB  - Superior mesenteric ganglia of six fetuses (35-40 weeks old) were investigated by
      histochemical fluorescent method. In addition to solitary SIF cells and clusters
      of SIF cells reported previously, a new structure of SIF cells was found and
      named "SIF-cell nodule". The SIF-cell nodule was composed of a large number of
      SIF cells and was encapsulated by dense connective tissue. Some blood vessels and
      nerve fibers entered the nodule. Based on the morphology, we speculated that SIF
      cell nodule might be an endocrine gland.

PMID- 7712842
TI  - A new insulin-sensitivity index for epidemiological study.

PMID- 7712844
TI  - Multiple organ dysfunction after heart valve replacement.
AB  - Multiple organ dysfunction (MOD) after valve replacement was studied in a period
      of 1980-1991. The incidences of MOD involving 2, 3 and 4 organs were 17.1%, 5.6%
      and 4.3% with corresponding mortalities of 12%, 18.5% and 76.2%. We focused on
      dysfunction of more than 3 organs, the dreadful complication, which can be
      divided clinically into three types: acute (type I), deteriorating (type II), and
      pulmonary infection (type III). In MOD, the function of heart and lung is
      primarily depressed after surgery. So the predisposing factors of MOD are acute
      pump failure and hypoxemia, and the possible triggering factor is infection,
      especially pulmonary infection, which re-endangers the organs recovering from the
      primary blows. Thus prevention of pulmonary infection is of same importance as
      treatment of pump failure and hypoxemia.

PMID- 7712843
TI  - Calcium supplementation during pregnancy for reducing pregnancy induced
      hypertension.
AB  - Pregnancy induced hypertension (PIH) is a common complication in pregnancy and
      prenatal stage. Because the direct and indirect relationship between low calcium
      intake and many diseases, such as rachitis, young age myopia and hypertension,
      calcium supplementation has been a hot topic among nutritionists. Randomized
      trials of calcium supplementation during pregnancy were conducted in 212 healthy
      primipara. They were divided into 4 groups and gave 120mg, 240mg, 1g or 2g of
      calcium daily from 20 to 28 wks of gestation up to delivery respectively. As a
      result, the incidence of PIH was 8.9%, 7.5%, 8% and 4% respectively in these
      groups. The control group (106 pregnant women) who did not receive calcium gave
      an incidence of 18%. Supplementation of 2g of calcium daily showed significant
      results in lowering the incidence of PIH (P < 0.05) without any adverse effects.
      In 1992 calcium supplementation was widely used in antenatal-clinic. 200 cases
      with intake of 2g calcium were compared with corresponding non-calcium
      supplementation cases, and the incidence of PIH was 7.5% and 16.5% (P < 0.005)
      respectively. Mediating parathyroid hormone and renin activity are thought to be
      the effect of calcium on decreasing the incidence of PIH.

PMID- 7712845
TI  - Effectiveness of electrochemical treatment of primary pulmonary malignant tumors.

PMID- 7712846
TI  - Progress in hand surgery of China.

PMID- 7712847
TI  - Present status of nephrology in China.

PMID- 7712848
TI  - [Surgical congresses and publications--is less more? Session of the 1994 German
      Surgical Congress in cooperation with the Professional Society of German Surgeons
      e. V. "Congresses--are there too many?" From the viewpoint of the surgeon].

PMID- 7712849
TI  - [Surgical congresses--are there too many? From the viewpoint of the Federal
      Association of the Pharmaceutical Industry].

PMID- 7712850
TI  - [Surgical publications--who can still read it all? From the viewpoint of the
      publisher].

PMID- 7712851
TI  - [Surgical publications--who can still read it all? From the viewpoint of the
      surgeon].

PMID- 7712852
TI  - [Endovascular and open reconstructive surgery of renal artery lesions].
AB  - Besides antihypertensive drug treatment and reconstructive surgery, the
      percutaneous transluminal angioplasty became an established treatment modality
      for renal artery stenosis since the late 70's. The treatment aimed at curing the
      renovascular hypertension, at normalizing and improving of both compensated and
      decompensated renal insufficiency in order to avoid prolonged hemodialysis after
      acute renal failure. Endovascular procedures contributed significantly to reach a
      normotensive state, particularly in cases with renal artery stenosis concomitant
      with fibromuscular dysplasia and gives similar results as open surgical methods
      if certain morphological features are considered. However, surgery is generally
      more effective than endoluminal treatment when all forms of renal artery stenosis
      are considered together. This holds true in particular for ostial stenosis,
      complete obstruction of the renal artery, aneurysms and a multitude of rare
      renovascular diseases. Surgery should be first line treatment to preserve or
      improve the renal function. According to the pertinent literature, endovascular
      methods should be considered first for the treatment of renovascular
      hypertension. Despite the frequent repetition of potential advantages of PTA, a
      first direct comparison of both modalities demonstrated better primary results
      after surgical treatment. Even the total cost were similar since PTA requires
      frequent follow-up with short intervals necessitating secondary interventions.

PMID- 7712853
TI  - [Aorto-intestinal fistula as a possible cause of endoscopically undetermined
      gastrointestinal hemorrhage].
AB  - Primary aorto-enteric fistulae are rare, mostly described as atypical first
      manifestation of an abdominal aortic aneurysm. Spread of elective aortic surgery
      led to increased appearance of secondary aorto-enteric fistulae as a typical
      postoperative complication. Gastrointestinal bleeding with endoscopical unclear
      findings in a patient with aortic aneurysm or history of aortic repair points
      towards an aorto-enteric fistula. While preoperative diagnosis is not possible in
      most instances, the proof of an anastomotic aneurysm and/or aortic graft
      infection hardens the suspected diagnosis of an aorto-enteric fistula decisively.
      The finding of coincidental mucosal lesions at gastroscopy may not mislead to
      give up the exclusion of an aorto-enteric fistula, possibly by explorative
      laparotomy, if suspicion is well-founded. In the present article nine cases of
      aorto-enteric fistulae treated at the Surgical University Clinic Wurzburg between
      1982 and 1993 are analyzed retrospectively. Topical questions of diagnosis and
      therapy are discussed.

PMID- 7712856
TI  - [Endoscopic dissection of perforating veins].
AB  - Endoscopic subfascial sectioning (ESDP) is an effective method for the
      interruption of incompetent perforating veins. From March 1993 to April 1994 27
      patients underwent ESDP in 35 legs. ESDP was performed in combination with
      Babcock's operation in 31 cases. Most patients demonstrated chronic venous
      insufficiency stage II or III (n = 25). A venous ulcer was found in 9 patients.
      Intraoperative complications were not seen. Postoperative complications were
      delayed wound healing (n = 1) and subfascial hematoma (n = 1). At follow-up
      examination after a mean interval of 8 months persistent insufficient perforating
      veins were seen in 3 of 88 Cockett veins (4%). A local dysesthesia of the
      saphenous nerve was found in 6 legs. Prior active venous ulcers had healed in 8
      of 9 cases.

PMID- 7712855
TI  - [Chylothorax after blunt thoracic trauma].
AB  - The diagnosis of chylothorax following blunt chest trauma is rare, only few cases
      have been reported. We describe three patients with chylothorax following blunt
      chest trauma. Conservative treatment consists of drainage, in severe cases
      mechanical ventilation with PEEP and total parenteral nutrition. In case of
      persisting and/or increasing chylus production, thoracotomy and ligation of the
      thoracic duct may be required. In all of our patients thoracostomy was the
      definite therapeutic modality, no thoracotomy was necessary.

PMID- 7712854
TI  - [20 years orthograde venous bypass for infrainguinal arterial reconstruction].
AB  - During a 20-year period (1973-1993) a series of 684 orthograde vein bypass
      procedures with the translocated greater (or lesser) saphenous vein was performed
      in 629 patients (422 male, 207 female) of whom 221 (35%) were diabetics. There
      were 499 femoro-popliteal grafts to the infrageniculate popliteal artery, 158
      femoro-crural and 27 popliteo-crural grafts. Indication for surgery was rest pain
      and/or tissue necrosis in 404, claudication in 277 and asymptomatic popliteal
      artery aneurysm in 3 extremities. All patients received long-term oral
      anticoagulation and were followed at regular intervals. At the concluding follow
      up (01-06/1993) graft function was investigated by colour flow duplex scanning
      and/or arteriography. Cumulative patient survival at 1, 5, 10 and 15 years was
      90.6%, 62.8%, 38.6% and 27.1%. Multivariate analysis (Cox-model) proved that
      preoperative clinical status (rest pain and tissue necrosis vs. claudication and
      asymptomatic popliteal artery aneurysm) (p < 0.0001) and diabetes (p < 0.001)
      were significant factors for survival. The 30-day patency rate was 93%, and the
      secondary cumulative patency rates (life-table method) were 85.7%, 78.6%, 73.8%
      and 65.9% at 1, 5, 10 and 15 years. Only the preoperative clinical status was a
      weak prognostic factor (Mantel p < 0.029) whereas diabetes or the level of
      proximal and distal anastomosis were without importance for graft performance.
      Cumulative limb salvage rates (life-table method) at 1, 5, 10 and 15 years were
      91.2%, 85.6%, 83.4% and 79.9% for the 404 legs operated for rest pain and or
      necrosis; and they were 100%, 98.8%, 97.7% and 94.9% for the 277 legs with
      claudication.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7712858
TI  - [Iliaco-crural bypass through a borehole in the iliac fossa as extra-anatomic
      vascular bypass in infected inguinal canal and posterior aspect of the knee].
AB  - In case of inguinal and medio-genual wound infections with menaced vitality of
      the lower limb, the extraanatomical, iliaco-crural bypass, passing a borehole in
      the iliac bone, seems to be a practicable procedure to secure perfusion. The
      distal anastomosis to the anterior tibial artery, as performed by the authors,
      can also be performed to the other arteries of the lower leg. This article
      reviews these indications as well as the technique of operation and short-term
      results.

PMID- 7712857
TI  - [Diagnostic score for acute appendicitis].
AB  - Scoring systems seem to be ideal for supporting diagnosis of acute appendicitis
      because they are non invasive, require no special equipment and can be used in
      clinical routine. Several scores for appendicitis have been developed with good
      results in the original publications. Unfortunately these good results could not
      be reproduced on a German data base. Therefore we developed a new score using
      multivariate statistics and a quality controlled prospective data base. The score
      covers 8 variables: tenderness, rebound tenderness, micturition, type of pain,
      leucocytes, age, relocation of pain, rigidity. Independent evaluation of the
      score on a Dutch database resulted in a negative appendicectomy rate of 21% and a
      missing appendicitis rate of 2%. The results are encouraging, so that further
      testing and clinical application can be recommended.

PMID- 7712859
TI  - [Video controlled, minimally invasive exposure of the abdominal aorta by
      retroperitoneal approach for aorto-iliac reconstructions].
AB  - The morbidity and mortality rate of aortoiliac reconstruction is significant even
      in patients who are at low risk undergoing aortic surgery. Beyond the general
      extent of vascular disease, the great surgical intervention using a large
      vertical midline or transverse abdominal incision is also responsible for this
      events. To decrease the surgical stress a new minimal retroperitoneal approach
      was developed. To exposure the infrarenal aortic segment a 7 cm left paramedian
      incision is used, a special retractor and modified surgical instruments combining
      direct visualization of the operation field with flexible videoendoscopic
      control. This new approach offers the possibility to decrease the operative
      stress and enables complete control if serious bleeding might occur. This
      'minimally invasive' approach appears to diminish the catabolic response and is
      hopefully associated with accelerated recovery and virtual abolition of large
      wound-related complications.

PMID- 7712860
TI  - [Congenital tracheoesophageal fistula in the adult].
AB  - Congenital esophago-tracheal and esophago-bronchial fistulae are rare. Symptoms
      are recurrent pneumonia, cough, dysphagia and pain. The diagnosis is made by
      bronchoscopy or esophagoscopy. Every time the diagnosis is certain, the fistula
      has to be exstirpated by means of a thoracotomy and plastic reconstructive flap
      surgery.

PMID- 7712861
TI  - [Cystic degeneration of the adventitia of the popliteal artery as a possible
      sequela of entrapment syndrome].
AB  - We report two cases of cystic adventitial degeneration of the popliteal artery in
      young sportsmen. The pathogenetic role of microtrauma is suggested by the
      localisation of the adventitial cysts, the clinical symptoms, as well as the
      immunohistochemical demonstration of foamy macrophages instead of endothelial
      cells in the wall of the cysts. In one case the cause of the intermittent
      claudication could be verified by duplex sonography and comparison of the
      arterial pressure of both legs with a Doppler method only after physical
      exercise. As expected, an angiodilatation has only a temporary effect. Therefore
      a surgical resection of the cyst or of the involved arterial segment had be
      performed.

PMID- 7712863
TI  - [Prognostic improvement by R1 and R2 lymphadenectomy in stomach carcinoma].

PMID- 7712862
TI  - [Malignant fibrous histiocytoma in the area of a total endoprosthesis of the hip
      joint].
AB  - Up to now 8 cases of malignant fibrous histiocytoma are reported in whom the
      tumor had developed after total hip replacement. Direct contact between tumor and
      prosthesis was proved in 7 cases. We report on a female patient of 74 years of
      age in whom a malignant fibrous histiocytoma of the gluteal region had formed 15
      years after total hip replacement. Tumor was located in the old operation scar.
      Not only a direct effect of the foreign material, but also the scar has to be
      regarded as an etiological factor in pathogenesis of malignant fibrous
      histiocytoma in these cases.

PMID- 7712864
TI  - [Open indications for endovascular surgery].
AB  - Endovascular techniques are becoming a part of minimally invasive surgery. The
      AIM is either preservation or reconstruction of the vascular lumen without the
      risk involved in conventional reconstructive procedures. The therapeutic success
      is often only palliative and not durable, because only the local cause of the
      disease is excluded and not removed definitively. Despite improvement in the
      technical equipment the indication for endovascular surgical treatment remains
      questionable and is the subject of experimental vascular research. Like other
      innovative procedures, the place for endovascular procedures will emerge in
      relation to the individual patient risk patient concerning age, concomitant
      diseases and cardiorespiratory conditions. In comparison to conventional
      reconstructive procedures endovascular techniques are being strongly pushed by
      specialists and industry because the risks of treatment are believed to be
      significantly lower. However, the risks of conventional vascular reconstruction
      are often overestimated and, as a rule, the failure rate in endovascular
      reconstructive surgery is often underestimated.

PMID- 7712865
TI  - [Endovascular and open reconstructive treatment of arterial occlusive disease of
      the lower extremity in the critical ischemia stage].
AB  - Arterial revascularization is mandatory in the vast majority of patients with
      critical ischemia in the leg. Open surgical and percutaneous catheter procedures
      (angioplasty, local thrombolysis, clot extraction) can each be applied alone or
      in combination to avoid major amputation. Given the low invasiveness and
      morbidity of percutaneous techniques, they should be the method of first choice,
      provided suitable occlusion morphology is available. If catheter therapy is not
      successful, surgery can be performed. Five-year patency after surgery for
      femoropopliteal obstructions is approximately 60% and 40% after catheter therapy.
      Iliac revascularization shows higher patency rates for both procedures.
      Percutaneous catheter techniques can be an alterative to vascular surgery, but
      more importantly both can be used as complementary procedures in the same
      patient, provided there ist good cooperation between the vascular surgeon and the
      person during the interventional angiology.

PMID- 7712867
TI  - [A 4-year retrospective study of neonatal outcome on preterm premature rupture of
      the membranes].
AB  - During a four year period, 60 patients with premature rupture of membranes (PROM)
      met the inclusion criteria of having a single living fetus with gestational age
      between 25 to 36 weeks and more than 24 hours between PROM and delivery were
      admitted in Karolinska Hospital, Sweden. These cases were reviewed
      retrospectively. Five neonates died postnatally and the total survival rate was
      91.7%. Three of them had major malformations and one died of hyaline membrane
      disease with 29 weeks of gestational age. In only one case the immediate cause of
      death was due to infection. The present protocol of expectant treatment for PROM
      in this hospital tends to be a minimum of unnecessary intervention for obtaining
      a high survival rate.

PMID- 7712866
TI  - [Results of vascular surgery reconstructions after PTA].
AB  - From 1986 through 1994 263 patients underwent vascular treatment due to 266 PTA
      complications. Complications at the site of the puncture were found in 35
      patients (13.2%), at the site of dilatation in 210 (78.9%), and due to macro
      embolism in 21 (7.9%). The most frequent pathology was thrombosis in 135 patients
      (50.7%). 62% of all operations were performed immediately or few days after PTA.
      The primary (secondary) patency rate after one month in AK femoro-popliteal
      reconstructions was 84% (88%), in BK reconstruction 69% (74%), after aorto-iliac
      reconstruction 90% (96.8%), in renal artery reconstructions 96% (96%), and in
      surgical interventions in the innominate artery and the subclavian artery 100%.
      In our opinion the unfavourable early results, especially after BK femoro
      popliteal reconstructions, are due to a deterioration of the run-off caused by
      peripheral microembolisation. Of the aorto-iliac and limb artery reconstructions
      7.1% required major amputation. The second most frequent complications were wound
      infections in 6.5%.

PMID- 7712869
TI  - [Breast-feeding by mothers with positive serum hepatitis B virus test].
AB  - Sixty one samples of colostrum from mothers with positive serum Hepatitis B virus
      (HBV) test were collected and determined for serial HBV markers along with HBV
      DNA. Results showed that HBsAg, HBeAg and anti-HBc were most likely transferred
      by milk, while anti-HBs and anti-HBe had less possibility to enter the colostrum
      (P < 0.01). The overall HBV DNA positive rate was 42.6% in the 61 samples. The
      various HBV markers detected in mothers' serum presented a high consistency with
      those discovered in the corresponding milk samples. There were significantly
      higher rate of milk HBV transmission from mothers with serum positive HBsAg,
      HBeAg and anti-HBc or either one of them than those with positive for anti-HBs
      and/or anti-HBe.

PMID- 7712868
TI  - [Analysis of risk factors of postpartum hemorrhage in rural women].
AB  - Sixty variables during pregnancy, labor and delivery of 951 rural women were
      analyzed to identify the risk factors of postpartum hemorrhage. The result showed
      that uterine atony (RR = 13.30, 95% CI = 8.23-21.50) and its related factors were
      the major risk factors of postpartum hemorrhage. The related factors included
      prolonged labor (3.49, 1.98-6.15), prolonged second stage of labor (2.72, 1.54
      4.78), pregnancy induced hypertension (mild 2.35, 1.11-4.99; > or = moderate
      3.04, 1.38-6.70), neonatal weight > or = 3.500 g (2.55, 1.66-3.91). Another
      category of postpartum hemorrhage risk factors were placental factors (6.32, 2.35
      17.01), the third stage of labor > or = 10 minutes (2.65, 1.74-4.01), parity > or
      = 2 (2.61, 1.69-4.01) and maternal age > or = 30 (2.19, 1.13-4.24). The authors
      recommends that the stress should be put on the management of labor and delivery,
      to prevent and management of postpartum hemorrhage, through training the birth
      attendants to promote their ability to prevent and manage uterine atony and
      correct management of labor and delivery.

PMID- 7712871
TI  - [Treatment of endometriosis with domestic luteinizing hormone--releasing hormone
      analogue].
AB  - Sixty patients with endometriosis, stage I-IV, diagnosed by laparoscopy or
      laparotomy, were treated with 200 micrograms of domestic luteinizing hormone
      releasing hormone analogue (LHRH-A) subcutaneously twice daily, starting from the
      early follicular phase for 6-10 months. Serum FSH and LH levels elevated at first
      declined significantly thereafter, and remained low after the sixth day of
      treatment. Serum E2 concentrations were suppressed below that of the early
      follicular phase or to the castrated levels after one month of therapy. Symptoms
      and signs of endometriosis improved markedly during the treatment and patients
      became anovulatory and amenorrheic. At the end of treatment, resolution of
      endometriotic implants and softening of adhesions were shown under the second
      laparoscopy. Endometrial biopsies revealed inactive endometrium. After
      discontinuation of the treatment, ovulatory menses returned within 34-72 days,
      more than half of the patients complicated with infertility for 2-10 years became
      pregnant within 1-8 months. The recurrence rate was 37% after 0.5-5 year follow
      up. Side effects were only related to hypooestrogenism. These data indicated that
      LHRH-A therapy had the effect of temporary reversible medical oophorectomy, and
      was therefore an effective approach for the treatment of endometriosis.

PMID- 7712870
TI  - [Fetal circulation in relation to various maternal body positions].
AB  - To determine the possible effect of various maternal body position on feto
      maternal circulation, we performed Doppler examinations on 50 women at different
      stages between the 27th and 40th week of normal pregnancy. Flow velocity
      waveforms of the umbilical artery, fetal descending aorta, and maternal uterine
      artery were recorded by pulsed Doppler scanner equipped with a 3.5MHz transducer
      (ALOKA SSD 680). The resistance index (RI) was calculated with the patient lying
      initially in the supine position, then 15 minutes later, in the lateral recumbent
      position. Maternal blood pressure, placental site, and fetal position were also
      assessed for possible relationship with the maternal position reflected by the
      resistance indices. The following results were obtained: (1) a negative
      correlation was observed between gestational period and umbilical artery flow
      velocity (r = -0.404, P < 0.05). (2) although up to the 37th week no outstanding
      difference was noted in the effect of maternal position on the flow velocity of
      the uterine and umbilical artery, from weeks 37 to 40, the resistance indices
      recorded in the supine position were significantly higher than those associated
      with the lateral recumbent position (P < 0.05). In the lateral recumbent
      position. Flow velocity of the umbilical artery was consistently in close
      correlation with that of the uterine artery. However maternal position had no
      bearing on the flow velocity in the fetal descending aorta; (3) no significant
      relationship was indicated between the flow velocity of the umbilical artery and
      blood pressure, placental site or fetal position.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7712872
TI  - [Detection of vaginal and cervical human papillomavirus by electronic microscope
      examination and polymerase chain reaction technique].
AB  - Forty-seven specimens, biopsied during April-July 1990, pathologically proven to
      be vaginal or cervical condyloma acuminata (CA) in 34, wart-like lesions in 6,
      infections in 7, were screened for detection of human papillomavirus (HPV) by
      electronic microscope (EM) examination and polymerase chain reaction (PCR)
      technique. HPV type 11 (HPV-11) infections were diagnosed by Dot-blot
      hybridization in 40 out of these 47 specimens. RESULTS: (1) No typical virus
      particles was observed in all samples under EM examinations. However,
      interchromatin and perichromatin granules were found within the nuclei of
      koilocytes in 88.23% of the vaginal CA specimens. Nuclear bodies were seen in 3
      out of 27 vaginal CA and HPV11 positive specimens. Furthermore, koilocytosis was
      also seen in the basal and parabasal layers of vaginal mucosa. (2) The positive
      rate for detection of HPV11 and HPV6 DNA by PCR technique in vaginal CA specimens
      was 92.6%, while positive rate for HPV 11, 6, 16 and 18 DNA was only 3.7%.

PMID- 7712873
TI  - [A clinical study 39 cases of ovarian pregnancy].
AB  - Thirty-nine cases of ovarian pregnancy in our hospital from 1982 to 1992 were
      analyzed, and compared with the tubal pregnancies admitted during the same
      period. It showed that the incidence of ovarian pregnancy was 2.6% of all ectopic
      pregnancies with a trend to increase yearly. The clinical features of ovarian
      pregnancy revealed that abdominal pain was the major symptom, and history of
      amenorrhea was obscure. The clinical diagnosis of ovarian pregnancy was more
      difficult than that of tubal pregnancy. The typical histologic characteristics
      showed the embryo and chorionic villi surrounded by ovarian tissue or the
      presence of decidual changes. Ovarian pregnancy was closely related with poor
      uterine environment, pelvic inflammatory disease and/or endometriosis. The
      preferred therapeutic procedure was partial ovariectomy or wedge resection,
      preserving the normal ovarian tissue and tube as much as possible.

PMID- 7712874
TI  - [Ovarian serous borderline tumor: the prognostic relation to the pathologic
      features and management].
AB  - The clinicopathological review of 49 cases of the serous borderline tumors (SBTs)
      of ovary with a follow-up of more than 20 years is presented. The results showed
      that there were no significant differences in the recurrence and the mortality
      rates between the SBTs and the SBTs containing foci of stromal microinvasion (P >
      0.05). The longterm survival rate of 40 cases with stage I was 97.5%, while stage
      III decreased to 33.3% (P < 0.01). The cause of 3 deaths was small bowel
      obstruction. No difference was found in the prognostic status and the mean
      survival years between total abdominal hysterectomy plus bilateral salpingo
      oophorectomy and unilateral salpingo-oophorectomy. 5 of 16 cases treated by
      unilateral salpingo-oophorectomy or cystectomy underwent normal pregnancies and
      deliveries during the follow-up period. These results suggest that SBTs
      containing foci of the stromal microinvasion did not affect the prognosis, they
      may have been taken as a subset of the ovarian SBTs. The malignant potential of
      SBTs is very low because of their excellent survival and the deaths only due to
      complications. Treatment should therefore be conservative in stage I cases,
      particularly in young women who wish for preservation of fertility functions.

PMID- 7712875
TI  - [The sensitivity of the CA125 immunoradiometric assay for patients with
      epithelial ovarian cancer and its correlation with complex treatment].
AB  - From 1988 to 1993, 141 patients with epithelial ovarian cancer were treated in
      our hospital. Histologically, tumors were: 69 serous, 16 mucinous, 6 clear cell,
      24 endometrioid, and 26 undifferentiated. Serial serum specimens were obtained
      from 50 patients at least 2 times in posttreatment 1 to 3 months to observe the
      correlation between CA125 levels and disease progression or regression. The
      result showed that CA125 levels were elevated (> 33kU/L) in 65/69 of serous, 0/16
      of mucinous, 6/6 of clear cell, 19/24 of endometrioid, 10/26 of undifferentiated
      tumors. The CA125 determinants was associated with the 80% of cases of
      nonmucinous epithelial ovarian cancer. Moreover, increases or decreases in CA125
      levels have been found to correlate well with disease progression or regression
      in more than 96% of instances. The determination of CA125 levels may aid in
      monitoring the response to treatment in patients with epithelial ovarian cancer.

PMID- 7712876
TI  - [Expression of human chorionic gonadotropin, human placental lactogen and
      pregnancy-specific 1-glycoprotein in malignant trophoblastic neoplasms].
AB  - The expression of placental hormones in 91 malignant trophoblastic neoplasms was
      studied immunohistochemically using a panel of antibodies against hCG, human
      placental lactogen (hPL) and pregnancy-specific 1-glycoprotein (SP). The results
      indicated that the expression of hCG in invasive moles was weaker than that in
      choriocarcinoma, but the expression of hPL and SP1 was stronger than those in
      choriocarcinoma. The expression of hPL and SP1 in the metastatic tumors of
      invasive moles was weaker than the expression at in the primary tumors, but the
      secretory capacity of hCG in metastatic choriocarcinomas was stronger than that
      in the primary neoplasms. In this study, the qualities of expression of the
      placental hormones in invasive moles and choriocarcinomas corresponded to the
      degree of tumor malignancy, the biological behaviour and the grading of
      trophoblastic cell differentiation. We believe that the detection of hCG, hPL and
      SP1, in malignant trophoblastic neoplasms was of value for establishing tumor
      diagnosis and typing and for judgement on prognosis.

PMID- 7712877
TI  - [Clinical analysis of 7 cases of parovarian borderline tumors].
AB  - Seven cases of primary parovarian borderline tumors are presented, Comprising
      1.6% of 451 cases of parovarian cysts treated. The age range of the 7 cases was
      from 16 to 60, with a mean value of 37 years. Abdominal mass, lower abdominal
      pain or discomfort were chief clinical complaints. In one case, because of
      amenorrhea of 2 months' duration, the preoperative diagnosis was mistaken to be
      extra-uterine pregnancy. Surgical examination revealed normal appearance of
      ovaries and fallopian tubes. Smooth-surfaced cystic masses arising from the broad
      ligaments were found in all of the 7 cases, their size ranged from 3cm x 2cm x
      1.5cm to 8cm x 8cm x 7cm. Internal papillary projections single or multiple, and
      clear serous fluid were seen in all of the 7 cystic specimens. Microscopically
      the cyst wall and papillary projections were lined with stratified cuboid or
      columnae epithelium. Abundant and complicated ramifications of the projections
      were seen. The nuclei showed slight to moderate metaplasia; mitoses were rare. 6
      of the cases originated from paramesonephros and 1 ease was of mesonephric
      origin. The seven patients were living and well during a postoperative follow-up
      period of 12 months to 11 years. Literature review on primary parovarian
      borderline tumors, their clinical presentation, pathological characteristics,
      therapy and prognosis are presented and discussed.

PMID- 7712878
TI  - [Advances in the research of endometriosis].

PMID- 7712879
TI  - [Uses of tamoxifen in gynecological diseases].

PMID- 7712880
TI  - [Morphological and functional changes of the human vascular endothelial cells in
      pregnancy induced hypertension patients].
AB  - Normal human vascular endothelial cells were cocultured with sera from pregnancy
      induced hypertension (PIH) patients. After staining it was found that sera from
      PIH patients could induce stress fibers production from the endothelial cells and
      which sometime destroy the integrity of normal monolayer structure of
      endothelium, thus result in endothelial damage. Sera from PIH patients could also
      induce intracellular adhesion molecules on the cell surface, thus result in the
      blood cells adhesion to vascular wall, and loss of endothelial cells from
      vascular wall under certain condition, thereby causing endothelial damage.

PMID- 7712881
TI  - [Plasma endothelin level in patients with pregnancy induced hypertension and its
      correlation with atrial natriuretic peptide].
AB  - Plasma levels of endothelin (ET) and atrial natriuretic peptide (ANP) were
      measured in 32 normal pregnant women and 26 patients with pregnancy induced
      hypertension (PIH). The correlation between ET and ANP were examined. This study
      indicated that the levels of ET and ANP in hypertensive pregnancy were higher
      than those of the normal pregnancy (P < 0.01). There was no correlation between
      ET and ANP in normal pregnancy (r = 0.18, P > 0.05), but significant inverse
      correlation in the patient with PIH (r = -0.57, P < 0.05). There findings
      suggested that ET may play an important role in the pathogenesis of PIH. An
      imbalance of increased amount of ET relative to deficient ANP may lead to PIH.

PMID- 7712882
TI  - [The effects of Salvia miltiorrhizae Bge and Ligustrazine on thromboxane A2 and
      prostacyclin in pregnancy induced hypertension].
AB  - The clinical efficiency and mechanism of traditional Chinese medicinal herb
      Salvia Miltiorrhizae Bge (SMB) and Ligustrazine (L) on pregnancy induced
      hypertension (PIH) were studied in 30 patients. Before and after the
      administration of SMB and L, the following parameters: mean arterial pressure
      (MAP), proteinuria, levels of Thromboxane A2 (TXA2) and Prostacyclin (PGI2) were
      observed. TXA2 and PGI2 were measured by their stable hydration products
      Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by an
      established radioimmunoassay. The results of treatment were compared with the
      base line values and showed as follows: MAP and proteinuria decreased
      significantly (P < 0.05); no marked difference existed in TXB2; the level of 6
      keto-PGF1 alpha increased significantly (P < 0.05); the rate of TXB2/6-keto-PGF1
      alpha decreased significantly (P < 0.05). The results suggested that SMB and L
      can invigorate blood circulation by decreasing vasoconstriction.

PMID- 7712883
TI  - [Lipid metabolism and pregnancy induced hypertension].
AB  - Lipid metabolism was studied in 30 healthy non-pregnant women, 35 normal pregnant
      women and 34 patients with pregnancy induced hypertension (PIH). Total
      cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL
      C), low density lipoprotein-cholesterol (LDL-C), LDL-C/HDL-C ratio, and athero
      sclerosis index (AI) were determined. In comparison with the non-pregnant status,
      lipid levels did not increased during normal mid-trimester pregnancy, but
      significantly increased at late trimester of normal pregnancy (P < 0.05). There
      was no significant difference in lipid levels between normal late pregnancy and
      PIH of mild and moderate degree, but TG and AI were significantly higher in cases
      with severe PIH. It showed that: lipid profiles in severe PIH was characterized
      by type IV hyperlipidemia; high lipid levels during normal late pregnancy might
      be a physiological phenomenon which presents a risk factor for PIH; marked
      increase of TG and AI in severe PIH may result in a rise of lipid peroxide (LPO).

PMID- 7712884
TI  - [Relation between histo-compatibility antigen immunogenetics and pregnancy
      induced hypertension].
AB  - Fourty cases with pregnancy induced hypertension (PIH) and 100 normal pregnant
      women were selected for this study. The distribution of histo-compatibility
      antigen D region (HLA-DR) frequency, the frequency of homozygosity and the HLA-DR
      antigens sharing between partners were investigated. The results showed that the
      frequency of HLA-DR4 was significantly higher in PIH than that in normal
      pregnancy (P < 0.001). There was a very high DR antigen sharing between partners
      in PIH as compared to normal pregnancy (P < 0.01), specially obvious in the
      frequency of DR4 antigen sharing in PIH (P < 0.0001). There was, however, no
      significant difference in the frequency of homozygosity or heterozygosity between
      HLA-DR and DR4 locus. This study suggested that HLA-DR4 may be related to the
      genetic susceptibility of PIH. This correlation is presumably due to a linkage
      imbalance of susceptible gene of PIH and DR4, but whether DR4 acts directly as an
      immunodeficient gene remains to be determined.

PMID- 7712885
TI  - [Evaluating cervical ripening in late pregnancy by transvaginal B-ultrasonic
      scan].
AB  - The ripening of the uterine cervix was studied by using trans vaginal B
      ultrasonic scanning against Bishop's scoring in 60 pregnancies in the 3rd
      trimester, yielding a conformity rate of 70%. All cases with a score > or = 6 by
      transvaginal B-ultrasound delivered naturally or shortly after induction. There
      were 22 cases shown immature by Bishop's scoring, of which, 18 found to be mature
      by B-ultrasonic scan. 5 of the 18 ended naturally and 13 following induction,
      while the 4 immature according to B-ultrasonic scan failed to come into labor.
      This proved that vaginal B-ultrasonic scanning is more accurate than Bishop's
      scoring. B-ultrasonic scanning on the perineum could display the internal
      cervical os but not the external, unless the body position was changed in
      different ways. Transabdominal B-ultrasound scanning did not clearly display the
      cervix and only one case revealed in the cervical canal, and the amniotic
      membrane. Thus, vaginal B-ultrasonic scanning has a higher rate of visualization
      and clearer pictures, being able to reflect correctly and objectively the
      cervical ripening, thereby providing a more reliable method for cervical ripening
      evaluation.

PMID- 7712886
TI  - [The value of saturated phosphatidylcholine determination in amniotic fluid of
      pregnancies in the third trimester].
AB  - The quantity of saturated phosphatidylcholine (SPC) in amniotic fluid was
      measured in 50 cases of normal late pregnancy and 21 women in labor, by improved
      Tsai's method. Normal values of SPC in different gestational weeks were obtained.
      The results showed that SPC in the amniotic fluid increased with the advancing
      gestational weeks and more significantly after the onset of labor. This study
      indicated that SPC determination can predict fetal lung maturity with high
      specificity, sensitivity and accuracy.

PMID- 7712888
TI  - [Clinical analysis of 5 cases of peritoneal mesothelioma].
AB  - Peritoneal mesothelioma is an infrequently encountered tumor that has a poor
      prognosis. Five female cases are reported in this article: one of epithelial
      type, one fibrous and three mixed, and there are two benign and three malignant
      cases. Abdominal mass, pain, ascites and weight loss are main manifestations. The
      epithelial and mixed types are prone to produce ascites. CT scanning is helpful
      for preoperation diagnosis. In 3 of the 5 patients the tumors have been
      thoroughly removed, one patient was treated with a partial removal, and one with
      biopsy only. Two patients have received chemotherapy after operation. The four
      patients who were given effective treatment survived each longer than 12 years,
      55 months, 26 months and 15 months. One of the 5 patients who received biopsy
      only at laparotomy died two months later. It is recommended that if the primary
      tumor of the organs in the peritoneal cavity could be excluded, any patient with
      an abdominal mass and ascites should be given the benefit of doubt that it might
      be a case of peritoneal mesothelioma. Laparotomy should be carried out, and all
      the visible tumor masses should be resected as completely as possible.
      Cytoreductive surgery should be done in patients with recurrence. If
      postoperative chemotherapy or radiotherapy is given the prognosis may be
      improved.

PMID- 7712887
TI  - [The clinical role of appendectomy in surgical procedures for ovarian cancer].
AB  - To assess the clinical role of appendectomy in the surgical procedures for
      ovarian cancer. We have evaluated retrospectively 96 cases of epithelial ovarian
      cancer treated from Aug. 1986 to Aug. 1993. In 19 cases the appendiceal
      involvement was pathologically confirmed (19.8%). All of the patients with
      appendiceal metastases were found in stages III-IV, with an incidence of 33.3%.
      There was no significant statistical difference between either the histologic
      type of ovarian cancer or the side (left or right) of the ovarian involvement and
      the incidence of metastasis in the appendix. We conclude, with these results,
      that the appendix was not a primary site involved in the early stages.
      Appendectomy is not to be regarded as a routine surgical procedures in the early
      I-II stages of ovarian cancer, but it may help to reduce residual disease in
      advanced patients.

PMID- 7712889
TI  - [Immunohistochemical study on estrogen receptors in conventionally formalin
      fixed, paraffin-embedded tissues of endometrial carcinoma].
AB  - Using specific monoclonal antibody to human estrogen receptors (ER), monoclonal
      antibody H222, with an avidin-biotin-peroxidase complex method,
      immunohistochemical localization of ER was performed on formalin-fixed, paraffin
      embedded tissues of 42 endometrial carcinomas. The paraffin sections were
      preceded by trypsin treatment to expose antigenic sites. Immunohistochemical
      evaluation incorporated both the intensity and distribution of staining into a
      semiquantitative analysis. Specific staining for ER was observed only in the
      nuclei of epithelial, stromal and malignant cells. No specific cytoplasmic
      staining was observed in all paraffin sections. ER-positive staining [histologic
      score (H-score) > or = 75] was found in 23 (54.8%) of 42 samples and the ER H
      Score of cancer components was significantly associated with the histological
      grade of endometrial carcinomas (P < 0.05). The ER-positive patients tended to
      have a better prognosis than ER-negative ones. Thus, it may be concluded that the
      treated formalin-fixed, paraffin-embedded tissues are still suitable for
      detecting ER by the immunohistochemical method, and the ER content of endometrial
      carcinomas is useful in indicating the differentiation of cancer and in
      predicting the patient's prognosis.

PMID- 7712890
TI  - [Anti-proliferative effects of tumor necrosis factor and gamma interferon on
      human ovarian cancer cell lines].
AB  - Two ovarian cancer cell lines, 3AO and NIH: OVCAR-3, were used in this study to
      assess the synergistic effect of TNF and IFN gamma in combination. The result
      showed that these two ovarian cancer cell lines were all resistant to TNF and IFN
      gamma individually, but sensitive to the combined administration of TNF and IFN
      gamma. Concentration of 1 x 10(4) U/L of TNF and IFN gamma significantly
      inhibited 3AO and NIH: OVCAR-3 ovarian cancer cells (P < 0.05). Administration of
      1 x 10(6) U/L TNF and IFN gamma could inhibit the growth of 3AO cells by 55% and
      NIH: OVCAR-3 cells by 75% (P < 0.01). It suggests that in some ovarian cancer
      cells which resistant to TNF could be changed to TNF sensitive cells by IFN
      gamma. anticancer treatment higher antitumor activity could be achieved by
      combined administration of TNF and IFN gamma.

PMID- 7712891
TI  - [Detection of cervical human papillomavirus infection from women with external
      genital condyloma acuminata].
AB  - Cervical biopsy specimens were taken from 36 women with external genital
      condyloma acuminata in order to diagnose a concomitant cervical human
      papillomavirus (HPV) infection. Positive HPV infection rate of cervix was 16%
      (6/36) by routine visual examination, 69% (25/36) by colposcopy and 56% (18/32)
      by pathology. Among those patients 31% (10/32) have grade I-II cervical
      intraepithelial neoplasia (CIN) according to pathology. In 8 cases, both vulva
      and cervical specimens were examined by Southern blot, dot blot and polymerase
      chain reaction (PCR) technique. HPV DNA positive was detected in 7 of 8 cervical
      specimens. It is concluded cervical HPV infection was rather common in women with
      external genital condyloma acuminata and it is valuable to examine cervical HPV
      infection by colposcopy and biopsy to detect the concomitant CIN.

PMID- 7712892
TI  - [Immunologic study on pregnancy induced hypertension].

PMID- 7712893
TI  - [Relation between placenta and pathogenesis of pregnancy induced hypertension].

PMID- 7712896
TI  - [Insulin resistance and pregnancy induced hypertension].
AB  - Plasma glucose and serum insulin in oral glucose tolerance test (OGTT) were
      measured in 40 patients with pregnancy induced hypertension (PIH) and 30 normal
      pregnancies. Compared with the controls, serum insulin concentration, plasma
      glucose and their area under the curve (AUC) increased in 15 patient with severe
      PIH, in 0.5, 1, 2, 3 hours postload (P < 0.05) of OGTT. The relationship between
      diastolic blood pressure and integrated area under the curve for serum insulin
      concentration (r = 0.35, P < 0.05) were observed in 15 patients with severe PIH.
      The results indicated that patients with severe PIH are insulin resistant and
      hyperinsulinemic after an oral glucose load.

PMID- 7712894
TI  - [Successful clinical pregnancy after transfer of frozen-thawed embryos].
AB  - A case of successful clinical pregnancy after transfer of frozen-thawed embryos
      was reported in this paper. The woman is a 45,XO karyotype Turner's syndrome
      patient with primary amenorrhea, and her husband has azospermia. She was given
      hormone replacement therapy to achieve adequate endometrial development. The
      donated embryos from two sources were frozen on April 27 and April 30, 1994
      respectively. The transfer was done on May 25, 1994. Urinary beta-hCG became
      positive 14 days later. On July 8th, an intra-uterine embryonic sac containing an
      embryonic bud with good primitive heart beats was seen under vaginal B
      ultrasound. Blood hCG reached 232,900 IU/L on July 25. The pregnancy is going on
      smoothly. The methods of freezing and thawing embryos were described.

PMID- 7712895
TI  - [Pathological study on placenta from pregnancies with systemic lupus
      erythematosus].
AB  - Pathological study on the placenta of 18 cases of pregnancy complicated with
      systemic lupus erythematosus (SLE) and 23 cases of normal pregnancy was done. The
      average weight and placenta-villi area ratio of the placenta from pregnancy with
      SLE were significantly lower than those of the normal (P < 0.05). Scanning under
      electron microscope showed the placental villi of the SLE group slender and
      branching little, with their ends bean-sprout looking and the surface covered
      with pin-point holes, even slitted masses. Immunohistologic examination indicated
      deposition of IgG, IgA, IgM, C3 on the villi capillary wall surface, which
      suggested damage of the placental function of the SLE gravidae by the immunologic
      compounds.

PMID- 7712897
TI  - [Influence of perinatal factors and sampling methods on thyroid stimulating
      hormone and thyroid hormone levels in cord blood].
AB  - The present study was designed to explore the influence of perinatal factors and
      sampling methods on fetal pituitary-thyroid axis. The results showed: (1) There
      was no linear relation between cord serum thyroid stimulating hormone (TSH),
      triiodothyronine (T3), thyroxine (T4) and either birth weight or the duration of
      labor (r = 0.03-0.12, P > 0.05). The mean cord serum TSH, T3 or T4 levels in the
      fetus delivered with uterotonic agents were no significant difference from those
      in fetus without these drugs and also there was no significant difference in the
      mean cord serum TSH, T3 or T4 levels according to the fetus sex (P > 0.05). (2)
      The mean cord serum TSH level of fetus in vacuum extraction group was
      significantly higher than that of fetus in normal vaginal delivery or caesarean
      section group (P < 0.01). However, the mean TSH levels of neonates on day 3-5 in
      heel blood spotted filter paper were no significant differences among the three
      groups (P > 0.05). (3) The mixed cord blood TSH level related quite well to the
      TSH level obtained from heel blood on day 3-5, or cord venous serum samples (r =
      0.67-0.84, P < 0.01). Our results suggest that measuring cord blood TSH level
      might be a feasible alternative method for neonatal congenital hypothyroidism
      screening.

PMID- 7712898
TI  - [Abnormal partograph in primipara with vertex presentation].
AB  - A prospective study on partograph (cross X type) was carried out in primipara
      with vertex presentation. There were 50 cases of dystocia in the study group and
      50 cases of normal delivery in the control group. The results showed that the
      latent phase and active period of labor course in study group was significantly
      longer than the control group (P < 0.001). The speed of cervical dilation and
      descent of fetal presentation in the study group was marked slower than the
      control group (P < 0.001). The rate of postpartum hemorrhage, total time of
      labor, operative delivery rate and neonatal asphyxia rate in the study group were
      significantly higher than the control group (P < 0.001). After active management
      38 cases in the abnormal group were delivered vaginally. It suggested that the
      use of partography is very important in revealing abnormal labor course and
      detection of dystocia, guiding the management of labor.

PMID- 7712900
TI  - [Intrasplenic metastasis of malignant ovarian tumor: clinical analysis of 12
      cases].
AB  - Intrasplenic metastasis of ovarian malignancies are uncommon. From 1986 to 1992
      only 12 such cases were diagnosed, being 1.2% of the total number of patients
      with ovarian malignancies treated in tumor hospital during the same period. Of
      the 12 metastasis, 6 were poorly differentiated. Diagnosis was made through
      imaging techniques or surgery. The median interval from the diagnosis of the
      primary disease to intrasplenic involvement was 28 months. The metastatic
      lesions, presented themselves as single or multiple nodes within the cortex of
      the spleen. Clinical features were not remarkable. It was thought that the
      occurrence of intrasplenic involvement might be due to greater tumor bulk, poor
      differentiation and decreased host immuno-competence caused by chemotherapy. Most
      of the intrasplenic metastasis was found after liver metastasis or simultaneously
      with the latter. The main route of the tumor spread might be via blood vessels.
      Sole intrasplenic metastasis can be treated by surgery with a temporarily good
      result. Poor prognosis and high mortality characterize intrasplenic metastasis.
      The median survival was only 7 months.

PMID- 7712899
TI  - [Differential diagnosis of endometrial abnormality by transvaginal sonography].
AB  - Transvaginal sonography examination was performed 450 times in 281 women to
      diagnose the endometrial abnormality by measuring the thickness of endometrium.
      There were 37 women with normal ovulatory cycles, 200 postmenopausal women with
      no vaginal bleeding, and 44 women with irregular vaginal bleeding. For ovulatory
      cycles, the mean of endometrial thickness was 7.8 +/- 2.1 mm (3-13 mm) in the
      follicular phase, 10.4 +/- 1.9 mm (8-13 mm) around ovulation and 10.4 +/- 2.3 mm
      (8-19 mm) in the luteal phase. The average thickness of endometrium for
      postmenopausal women without bleeding was 1.4 +/- 0.7 mm (1-5 mm). The
      measurement of the thickness of endometrium in women with irregular vaginal
      bleeding was also confirmed by histological analysis. Atrophy endometrium was
      diagnosed in 6 cases, the thickness of endometrium was 2.2 +/- 2.0 mm,
      hydrohystera was found in 8 women, thickness of endometrium was 14.5 +/- 6.1 mm,
      endometrial hyperplasia in 10 cases, thickness was 17.4 +/- 6.7 mm, endometrial
      polyps in 12 cases, thickness was 16.7 +/- 7.7 mm, and endometrial carcinoma in 8
      cases, thickness was 24.4 +/- 11.9 mm. Generally, the normal thickness of
      endometrium for postmenopausal women should be less than 5.0 mm.

PMID- 7712901
TI  - [Circadian rhythm in susceptibility of mice to the anti-tumor drug carboplatin].
AB  - The platinum-containing compounds has become a major chemical agent in the
      treatment of cancer. A circadian rhythm in the susceptibility of rodents and
      human being to cisplatin has been demonstrated, the maximal tolerance being found
      in the animal's active phase. Carboplatin is a second generation analog. Two
      studies were performed on mice with carboplatin under 12:12 light dark cycle to
      study its chronotoxicity and chronoeffectiveness. In study I, single
      intraperitoneal injection of 192mg/kg (LD50) carboplatin was given to four groups
      of mice at four different circadian stage. It was found that at 50% the overall
      mortality of mice, there was a mortality difference of 28% for mice receiving the
      drug at 9 a.m. to 71% for mice receiving drug at 9 p.m. It demonstrated that
      carboplatin was better tolerated in the animal's early sleep phase. In study II,
      S180 tumor-bearing mice were treated with 50mg/kg of carboplatin. The longest
      mean survival time and the lowest marrow toxicity occurred in the group which
      received the drug at the beginning of the sleep phase. It showed that the
      susceptibility of mice to carboplatin is circadian stage dependent. These data
      clearly demonstrate that, by timing the administration of drugs according to body
      rhythms, such as the host susceptibility-resistance rhythm to a drug, one can
      gain a therapeutic advantage over an approach which ignores such rhythms.

PMID- 7712902
TI  - [Analysis of complications associated with catheter intraperitoneal chemotherapy
      of ovarian carcinoma].
AB  - 115 patients suffering from ovarian carcinoma were admitted from May 1976 through
      August 1991, and were treated with intra-peritoneal chemotherapy. A total of 191
      catheters which with 2mm in diameter and 50 cm in length were inserted with 608
      courses of chemotherapy. 29 plastic catheters used by 29 patients were kept for
      18.4 days averagely, while 162 silica catheters used by 86 patients were kept 109
      days in average. The duration of keeping silica catheters was significantly
      longer than plastic catheters (P < 0.01). Complications were found in 29
      patients, 25.2% of the total: 5 cases of infection (4.3%), 2 of partial
      intestinal obstruction (1.7%), 4 of painful sensation (3.5%), 12 with inflow
      obstruction (10.4%) and 6 with falling off of the catheters (5.2%). Complications
      between the two groups were compared. There was no statistical significance (P <
      0.05). When catheter retainment times of the two groups were compared,
      significant differences were found between plastic and silica catheters (P <
      0.001). Our results indicate that both kinds of catheters may be used in
      intraperitoneal chemotherapy of ovarian cancer patients, and the silica ones seem
      better.

PMID- 7712903
TI  - [Termination of early pregnancy by two regimens of mifepristone with misoprostol:
      a multicentre clinical trial].
AB  - Six hundred women in early pregnancy (< 49 days), who requested medical abortion
      were randomly allocated into 3 groups. In group 1 (n = 301), an initial dose of
      mifepristone 50 mg was given, followed by 25 mg every 12 hours up to a total dose
      of 150 mg mifepristone, plus a single oral dose misoprostol 600 micrograms in the
      morning of the third day. In group 2 (n = 150), the same regimen of mifepristone
      was given, but dl-15-methyl-PGF2 alpha (PG05) 1 mg vaginal suppository was
      inserted on the third day. In group 3 (n = 149), a single dose of mifepristone
      200 mg was given and misoprostol 600 micrograms was used as in group 1. The
      complete abortion rate were 95.3%, 97.3% and 95.4% incomplete abortion rate were
      3.0%, 2.0% and 2.6% for group 1, 2 and 3, respectively. No significant difference
      of the two rates was shown among these 3 groups approximate 82% of the women had
      lower abdominal pain. The overall, occurrence of diarrhea in PG05 group (38.7%)
      was significantly higher than that in the other 2 groups (21.6 and 20.1%,
      respectively) (P < 0.001), and so was the occurrence of vomiting. It was
      concluded that misoprostol, as an orally-effective prostaglandin, in combination
      with 2 regimens of mifepristone for induced abortion during early pregnancy was
      as effective as PG05 vaginal suppository. In addition, it has the advantages of
      convenience for use, less side effects, easy storage and transfer, and low cost.

PMID- 7712904
TI  - [Histopathology appearance of intrauterine residue after medical abortion by
      mifepristone and prostaglandin analogue].
AB  - Four hundred and fifty pregnant women were recruited for termination of early
      gestation by mifepristone combined with dl-15-methyl PGF2 alpha or misoprostol.
      Eight-four out of 450 subjects received curettage because of heavy or prolonged
      vaginal bleeding and slow decline of urinary hCG levels. Histopathology
      examinations of specimens obtained during curettage revealed denatured, necrotic
      and obscure villi and trophoblasts in 77 specimens, which accounted for 91.7%.
      Among them, 68 samples were mingled with inflammatory cell infiltration, and 15
      with decidual cells, only 3 were villi and trophoblasts alone. The remaining 7
      specimens were decidua in 6 and inflammatory infiltration in 1, which accounted
      for 7.1% and 1.2% respectively. This study suggested that the major cause
      resulting in heavy or prolonged vaginal bleeding after medical abortion by
      mifepristone and prostaglandin analogue was residual villi and trophoblasts with
      inflammatory cell infiltration.

PMID- 7712905
TI  - [Current status and prospects of chemotherapy of ovarian cancer].

PMID- 7712906
TI  - [Electron microscopy plays an important role in the pathological diagnosis of
      renal diseases].

PMID- 7712907
TI  - [Prevention and treatment of the involutional osteoporosis in the elderly].

PMID- 7712908
TI  - [Essential hypertension: a predictor of the 6 year-incidence of NIDDM in 465 non
      diabetics].
AB  - The effect of essential hypertension at baseline on the development of NIDDM
      within 6 years was investigated in 465 Chinese nondiabetics with or without
      hypertension. The age, sex adjusted 6 year incidence of NIDDM in hypertensive
      group (BP > 18.7 +/- 12. okPa (140/90 mmHg) or treated with antihypertensives) at
      baseline was significantly higher than that in normotensive group (44.6%, n =
      325, P < 0.05) at baseline. Multivariate regression analysis showed the
      hypertensive group had higher risk of worsening to diabetes compared with
      normotensives (OR: 1.82, 95% Ci: 1.03-3.21, P < 0.05) after the adjustment for
      two other important risk factors for NIDDM, the fasting plasma glucose and BMI.
      Further more the increasement of SBP by 20 mmHg at baseline significantly
      increase the risk for NIDDM in the followup period in the blood-lowering-drug
      free group (OR: 1.54, 95% Ci: 1.05-2.24, P < 0.05). Thus it confirmed that
      hypertension at baseline was an independent predictor for NIDDM. In addition, our
      observation showed that some antihypertensive drugs appears also to play an
      unfavorable role in the occurrence of NIDDM.

PMID- 7712909
TI  - [Iatrogenic osteoporsis: six case reports].
AB  - Iatrogenic osteoporosis is a very common secondary osteoporosis is found in
      patients treated with large dosage of glucocorticosteroid of long duration. Six
      cases listed in this article including 2 cases of bronchial asthma, 2 cases of
      bronchial asthma, 2 cases of rheumatoid arthritis, 1 case of skin disease and 1
      case of callagenosis (three male patients and three female patients). The age is
      from 27-46. The duration of treatment of primary disease with glucocorticosteroid
      is 1 to 3.5 years, with the average of 1.56 years. With the exception of one case
      treated with Dexamethasone one of 0.75g daily, the other 5 cases are treated with
      predinisone of 5-30mg daily. After they treated with hormone every other day and
      added Calcium and vitamin D and followed up 1 year, the mineral contents in the
      bone of all 6 patients are increased and the biochemistry indexes are improved.

PMID- 7712910
TI  - [Clinical trial of indapamide in the management of central diabetes insipidus].
AB  - To investigate antidiuretic effect of indapamide, ten patients with central
      diabetes insipidus (CDI) were observed with the treatment of 2.5-7.5 mg of
      indapamide per day. After the third day of therapy, their mean daily urine output
      reduced by about 50%, and urine osmolality increased 1.36 times. No further
      change was seen in urine volume and urine osmolality on the sixth day of
      treatment. This antidiuretic effect was similar to that of 50-75 mg
      dihydrochlorothiazide per day. No adverse reaction was observed in blood pressure
      and serum potassium concentration during indapamide therapy. These data suggest
      that indapamide may be a new drug in the management of CDI.

PMID- 7712911
TI  - [Pulmonary nocardia infection].
AB  - Four cases of pulmonary Nocardia infection were reported and the 22 cases
      reported in our country between 1980 and 1993 were analyzed together for the
      purpose of revealing the clinical picture of this disease in China. There was
      approximately a ratio of two male patients to one female (18:8) with a mean age
      of 40 years in this series of patients. Various underlying diseases were found as
      predisposing factors in 69% (18/26) of the cases. 34.5% (9/26) of the cases had a
      history of corticosteroid therapy. Pleural effusion was identified in 50% (13/26)
      of the patients. 38% (10/26) of the patients died. Patients with primary
      pulmonary Nocardia infection had a better prognosis than those with secondary
      infection. Appropriate culture media, sufficient culture time and repeated
      cultures were recommended to improve the positive identification rate of this
      special causative agent. The sulfonamides were the drugs of first choice along
      with prompt drainage of thoracic empyema and abscess.

PMID- 7712912
TI  - [Detection of P-glycoprotein expression in patients with acute leukaemia and
      clinical significance].
AB  - Anti-P-glycoprotein monoclonal antibody JSB-1 and alkaline phosphatase-anti
      alkaline phosphatase (APAAP) immunocytochemical staining technique were used to
      study the relation between P-glycoprotein expression and clinical multidrug
      resistance (MDR) in 42 patients with acute leukaemia (23 ALL and 19 ANLL). 10 of
      17 patients who were diagnosed as refractory or relapsed acute leukaemia were
      positive with P-glycoprotein expression, while only 3 of 14 newly diagnosed and 1
      of 11 who were in complete remission were positive. The preliminary results
      indicated that there was a close association between the P-glycoprotein
      expression and the clinical resistance to chemotherapy in some patients.

PMID- 7712913
TI  - [Leukemia associated with bimkolane].
AB  - Psoriatic patients and mice treated with bimolane were observed. The frequency of
      chromosomes aberration and micro-nuclear cells presence in the treated group (11
      cases) was significantly higher than that in the control group (11 cases, P <
      0.005; < 0.001). Study of lymphocytic subsets showed that value of CD4/CD8 in the
      peripheral blood of the treated group was lower than that of the control group (P
      < 0.05). The level of serum IgM in the treated group was also lower (P < 0.05).
      There were 10 mice suffering from leukemia (7 mice with acute promyelocytic
      leukemia) in a treated group of 40 mice of an inbred line of 615 mice, while
      there was no leukemia in a control group of 20 mice of the same species. The
      morbidity of leukemia in the treated mice was higher than that of controls (P <
      0.05).

PMID- 7712914
TI  - [Tumor necrosis factor alpha levels in patients with chronic liver diseases and
      its relationship to pathogenesis].
AB  - Tumor necrosis factor alpha (TNF alpha) was measured with an enzyme-linked
      immunosorbent assay. TNF alpha levels in peripheral blood of patients with twenty
      one cases of chronic persistent hepatitis (7.3 +/- 9.5 micrograms/L), fourty-two
      cases of chronic active hepatitis (15.4 +/- 31.1 micrograms/L), one hundred and
      six cases of liver cirrhosis (11.1 +/- 17.7 micrograms/L) and one hundred and ten
      cases of parimary hepatocellular carcinoma (10.9 +/- 13.3 micrograms/L) was
      significantly increased when compared with normal controls (4.3 +/- 2.9
      micrograms/L) (P < 0.01). There was significant correlation between tumor
      necrosis factor alpha levels and ALT elevation and also between TNF alpha levels
      and bilirubin contents more than 100 mumol/L in chronic hepatitis patients. Tumor
      necrosis factor alpha levels was also significantly in HBV concomitant with HCV
      and/or HDV infection than in HBV infection alone. There was no correlation in
      tumor necrosis factor alpha levels and AFP concentrations. These findings show
      that tumor necrosis factor participates in the activity process of liver disease.

PMID- 7712916
TI  - [Diagnosis of endomyocardial fibrosis with endomyocardial biopsy].
AB  - Ten cases of endomyocardial fibrosis (EMF) were diagnosed with angiocardiography
      in showing a huge right atrium' tricuspid regurgitation and obliteration of right
      ventricular apex. The diagnosis was confirmed in 9 of them pathologically after
      right ventricular endomyocardial biopsy (EMB) in showing striking thickening of
      endocardium with presence of fibrosis. The remaining case was not confirmed with
      EMB. It is concluded that EMB is a quite useful method in the diagnosis of EMF.
      The cause of misdiagnosis in the tenth case was discussed.

PMID- 7712915
TI  - [Clinical significance of immunohistochemistry and ultrastructural change of
      myocardium in viral myocarditis].
AB  - Endomyocardial biopsy (EMB) specimens from 56 patients with suspected viral
      myocarditis (VMT) were studied. With microscopical study of the EMB specimens
      stained with HE, 14 of the 56 cases were diagnosed as myocarditis (25%) and 24 as
      non-myocarditis (43%). But immunohistochemistry stain showed that the contents of
      myosin, actin and myoglobin reduced in 51 patients (91%). Ten of 56 specimens
      were observed under electron microscope (EM). EM examination revealed focal or
      diffuse lysis of myofibrils in 10 patients. The results showed that: (1) The
      myofibrils in VMT showed severe damage. (2) Immunohistochemistry and EM
      examination can be used as a supplement to the Dallas diagnosis standard in order
      to improve accuracy of EMB in diagnosing VMT.

PMID- 7712917
TI  - [The effect of hydrocortisone or dexamethasone on human erythrocyte membrane
      insulin receptor].
AB  - It is shown that the maximum specific binding rate (B/T) of erythrocyte membrane
      receptor to insulin was significantly decreased, the concentration of plasma
      insulin was significantly increased and the level of plasma glucose was not
      obviously changed after taking hydrocortisone (1.25mg/kg) or dexamethasone (37.5
      micrograms/kg) orally. Scatchard analysis showed that decreased B/T was not
      mainly due to the change of the affinity or number of foci of insulin receptors,
      as no significant influence on insulin binding was found in vitro. The data
      suggested that the effect of both drugs on insulin receptor was multifactorial,
      including the secretion of insulin as well as the combination of insulin to its
      receptors.

PMID- 7712918
TI  - [A clinical study on low dose cyclosporin A in the treatment of lupus nephritis].
AB  - The aim of this study is to compare the effects of low dose cyclosporin A (CsA)
      and intravenous cyclophosphamide pulses (IV-CTX) in the treatment of lupus
      nephritis (LN). Thirty patients were included in the study with 15 in each group.
      The improvement of ESR and proteinuria and the increase of serum albumin were
      observed in the CsA group, but not in the IV-CTX group at the early stage of the
      therapy, though the overall effects were similar. The conclusion is that the use
      of low dose CsA could quench the activity of LN at the early stage of the
      therapy, reduce the doses of steroid and CTX and minimire their side effects. IV
      CTX was added to 8 cases of LN before CsA treatment had been tapered of or
      withdrawn. The results indicated that this regimen could effectively prevent the
      relapse of LN after the withdrawal of CsA therapy. It is an effective and
      valuable therapy.

PMID- 7712920
TI  - [Anti-neutrophil cytoplasma antibodies and vasculitis].

PMID- 7712919
TI  - [Evaluation of plasma neuropeptide Y levels in patients with congestive heart
      failure].
AB  - Plasma neuropeptide Y (NPY) was measured by radioimmunoassay in 43 patients with
      congestive heart failure (CHF) and 20 healthy control subjects. The results
      showed that plasma NPY levels were elevated in patients with CHF compared with
      control subjects (366 +/- 28 ng/L VS. 89 +/- 22 ng/L, P < 0.001). There was a
      close relationship between the severity of CHF and plasma NPY levels. The severer
      the CHF, the higher the NPY level. In addition, 20 of the 43 patients with
      symptoms improved after treatment for heart failure were followed. The results
      indicated a significant decrease of plasma NPY levels (333 +/- 42 ng/L VS. 157 +/
      25 ng/L, P < 0.01) in these patients. Furthermore, multiple logistic regression
      analysis demonstrated that the presence and severity of CHF were related to
      plasma NPY levels significantly and independently. Because of its potent
      vasoconstrictive and negative cardiac inotropic effects, NPY might be involved in
      the pathophysiology of CHF. Plasma NPY levels might be taken as a prognostic
      indicator in patients with CHF, but further investigation is needed.

PMID- 7712921
TI  - [Morphological typing of bone marrow biopsies in acute leukemia].

PMID- 7712922
TI  - [Hepatitis associated aplastic anemia].

PMID- 7712923
TI  - [Experimental research on treatment of acute organophosphorus insecticides
      poisoning with high-dose atropine: upregulation of muscarinic receptor].
AB  - Acute organophosphorus insecticides poisoning (AOIP) is a common medical
      emergency. There is, at present, a tendency to use high-dose atropine treatment
      (HDAT). This study aims to test if, during AOIP, HDAT would cause upregulation of
      muscarinic receptor (M-R). Male mice of the same batch and strain were raised,
      randomly divided into 3 groups and orally fed with DDVP of the same dose. HDAT
      for 7 days was given to group A, HDAT for 36 hours was given to group B and low
      dose atropine treatment for 36 hours was given to group C. Then radionuclide
      assay was employed to measure the M-R in the brain and atrium of the mice in each
      group. The results were that, compared with a control group, the Bmax values
      (fmol.mg protein-1) of M-R in groups A and B were increased significantly (P <
      0.01), while that in group C showed no evident change (P > 0.05). These results
      indicate that HDAT leads to some physiological change in the body, which may be
      responsible for the development of poisoning rebound and atropine dependence.

PMID- 7712924
TI  - [Neuropsychiatric disturbances and neuro-electrophysiological examination in
      patients with arsenic poisoning].
AB  - Neuropsychiatric disturbances caused by arsenic poisoning in 28 patients were
      reported. The incidence was 32.2% of all the arsenic poisoning patients. The
      patients were classified into three types according to their clinical symptoms.
      The neurologic type constituted 46.4%, mental type 21.4% and mixed type 32.1% of
      the patient respectively. Various abnormalities were found in EEG, EMG, EP and
      EKG examination. EMG and EP were still abnormal in most of the patients after
      treatment for three months. The results showed that arsenic poisoning may cause
      neuropsychiatric disturbances. The symptoms in these patients are serious and the
      recovery is quite slow.

PMID- 7712925
TI  - [Labial salivary gland biopsy in the diagnosis of Sjogren's syndrome].
AB  - Labial salivary gland biopsy (LSG-B) along with Schirmer test and kerato
      conjunctival staining with fluorescein dye was performed in 196 patients with
      suspected Sjogren's syndrome (SS). Of the 196 patients, 117 were found to have 2
      or more lymphocytic focus scores (LFS/4mm2) on their LSG-B specimens. 92 of them
      having keratoconjunctivitis sicca (KCS) as well met the diagnostic criteria of
      SS. Among the cases (25) without KCS, 16 with another CTD were diagnosed as
      secondary SS. 9 cases were classified as probable primary SS in this study
      because they had clinical manifestations of SS. Of the 11 cases with KCS only, 6
      with another CTD were diagnosed as secondary SS; 5 befitted primary SS for
      abnormal findings on sialography. We also found that lymphocytic infiltration in
      LSG-B was much more severe in primary SS than in secondary SS; this could be
      attributed to the use of immunotherapy for the accompanying CTD in secondary SS.
      There was good association in our study between the severity of lymphocytic
      infiltration and systemic involvement.

PMID- 7712926
TI  - [The abnormalities of the cellular immunity in rheumatoid synovium].
AB  - With the technique of immunohistochemical (ABC) method monoclonal antibodies were
      used to identify the lymphocyte subsets, macrophage and the expression of class
      II MHC (HLA-DR, HLA-DQ) antigens in the synovium cells from 18 RA patients and 8
      patients with osteoarthritis as control. The results showed that the main
      cellular abnormality at the sublayer of the synovium was the appearance of
      lymphoid follicles which mainly consisted of the infiltration of T lymphocytes
      (77.8%).50.6% of them were CD4+, which mainly consisted by of CD45RO+ cells in
      the rheumatoid synovium on the consecutive sections. The increased ratio of
      CD4/CD8 in RA patients was significantly higher when compared with that in the
      controls (2.11 +/- 0.93 vs 0.63 +/- 0.13, P < 0.001). In advanced RA with
      fibrosis of joints, the ratio tended to decrease and was accompanied with
      reduction of infiltrated lymphocytes. Compared with T cells CD20+ B lymphocyte
      not only had a lower percentage (25.2%), but also showed a characteristic picture
      of locating in the centre of the follicles. The fact that most of the CD4+ T
      cells was helper memorized lymphocytes with CD4 phenotype of positive TAC(+)
      (interleukin-2 receptor) and that up to 54.2% was anti-HLA-DR and 54.1% anti-HLA
      DQ monoclonal antibodies indicated that these T lymphocytes were activated in
      vivo. Cells with anti-CD68+ were seen all over the RA synovium. Class II HLA and
      CD68 molecule were also expressed on the endothelium cells of the small vessels.
      It is suggested that the activated lymphocytes, macrophages and endothelium cells
      and their abnormal distribution may indicate the abnormalities of the cellular
      immunity in rheumatoid synovium.

PMID- 7712927
TI  - [The changes of urine protein and serum beta 2-microglobulin in autoimmune
      thyroid disease].
AB  - Because of the different observed results about the microproteinuria in
      autoimmune thyroid disease, serum B2-MG, urine B2-MG, albumin and immunoglobin by
      RIA in 39 untreated autoimmune thyroid disease (AITD) (28 with Graves disease and
      11 with Hashimoto disease) had been observed. Micro-proteinuria was found in
      28.6% of patients with Graves disease and in 45.5% with Hashimoto disease; Serum
      B2-GM concentrations were significantly increased in Graves disease compared with
      that of controls. Our results suggest that the lesions present in both glomerulus
      and tubulus in AITD. The mechanism of them had been discussed in this paper.

PMID- 7712928
TI  - [Antibiotic treatment for pneumonia caused by Flavobacterium meningosepticum].
AB  - Two cases of critical nosocomial pneumonia caused by flavobacterium
      meningosepticum (FM) were reported and both of them were successfully cured.
      There were 2 other cases of FM pneumonia reported in Chinese literature
      previously, but none of them survived. It has been found that the treatment for
      FM respiratory infection was very difficult because of its resistance to majority
      of antibiotics, including the third generation cephalosporins. The symptoms of FM
      pneumonia are similar to those of other gram-negative bacillus pneumonias, such
      as Klebsiella pneumoniae pneumonia. Definite diagnosis depends principally on
      etiological examination and clinical manifestations of pneumonia. Cefoperazone,
      Cefsulodin, Astreonam and Ciprofloxacin are valuable drugs in saving the lives of
      patients with FM Pneumonia.

PMID- 7712929
TI  - [POEMS syndrome--a report of eight cases and review of literature].
AB  - POEMS syndrome is an unusual multisystem disorder associated frequently with
      polyneuropathy, organomegaly, endocrinopathy, M-protein change and skin lesion.
      POEMS is the acronym the above-mentioned clinical manifestations. The patients
      who were diagnosed must have at least three of the manifestations; polyneuropathy
      and plasmagenic disorders are almost always present. We present in this paper
      eight patients, their clinical symptoms, laboratory tests and treatment were
      analysed and discussed.

PMID- 7712930
TI  - [The emergency treatment of organophosphorus pesticides poisoning].

PMID- 7712931
TI  - [The actions of leukotrienes on the cardiovascular system].

PMID- 7712932
TI  - [Long-term treatment with quinapril in chronic aortic and mitral insufficiency].
AB  - The effect on myocardial function and structure of long-term administration of
      quinapril (10-20 mg daily), an angiotensin-converting-enzyme (ACE) inhibitor, was
      investigated in 24 patients (18 men, 6 women; mean age 48 [20-65] years) with
      chronic isolated asymptomatic aortic or mitral regurgitation. Coronary heart
      disease had been excluded angiographically. After one year's treatment the
      regurgitation fraction, compared with the pretreatment value, had decreased by
      27% in those patients with aortic regurgitation (AR) and 42% in those with mitral
      regurgitation (MR) (P = 0.0001). The mean left ventricular enddiastolic volume
      was reduced from 150 +/- 33 to 128 +/- 30 ml/m2 in patients with AR, from 146 +/-
      26 to 109 +/- 24 ml/m2 in those with MR (P = 0.0001). The mean endsystolic volume
      fell from 55 +/- 27 to 44 +/- 28 ml/m2 in patients with AR and from 63 +/- 43 to
      47 +/- 29 ml/m2 in those with MR (P = 0.002). The mean left ventricular ejection
      fraction at rest and on exercise rose slightly in patients with AR, remaining
      unchanged in those with MR. The left ventricular mass, as measured by
      echocardiography, was reduced by 35% in patients with AR, and the left
      ventricular hypertrophy, demonstrated in all patients, regressed. In patients
      with MR the left ventricular mass decreased by 15% and septal thickness became
      normal (borderline hypertrophy). These data indicate that, after one year's
      treatment with quinapril, left ventricular dilatation, mass and hypertrophy
      regressed and left ventricular function improved in patients with AR or MR.

PMID- 7712933
TI  - [Segmental small intestine lesions after taking non-steroidal antirheumatic
      drugs].
AB  - Over a period of 7 months a 51-year-old diabetic took mefenamine acid (up to
      500mg 20 times daily), diclofenac and, more rarely, paracetamol for lumbosacral
      pain. In addition, dexamethasone (4 mg three times daily) was prescribed later.
      For 4 weeks he had colicky abdominal pain which then started acutely to radiate
      into the flanks. Pressure and rebound pain in the left epi- and mesogastrium, as
      well as the results of biochemical tests, suggested an acute abdomen. Abdominal X
      rays, selective contrast examination of the small intestine and computed
      tomography demonstrated changes within some segments of the jejunum (thickened
      wall, irregular wall surface). Laparoscopy showed brown discoloration of the
      loops of the small intestine. In consequence of these findings a 10 cm long
      segment of the jejunum was resected. Histological examination showed extensive
      ulcers at the tip of the rugae with granulating inflammation and bifringent
      foreign bodies with giant-cells. The villi were extensively atrophied, the blood
      vessel were congested and the submucosa fibrosed. The patient was discharged
      after 9 days and, no longer taking NSAIDs, has been free of abdominal symptoms.

PMID- 7712935
TI  - [Diagnosis of chronic constipation].

PMID- 7712934
TI  - [Treatment of thrombotic thrombocytopenic purpura (Moschcowitz's disease) with
      vincristine].
AB  - A 64-year old female had been diagnosed as having thrombotic thrombocytopenic
      purpura (TTP; Moschcowitz syndrome) in 1984. The initial episode and one
      recurrence 5 years later were successfully treated with fresh plasma transfusions
      without plasmapheresis. Two days before the present admission, she noticed pain
      in the knee and haematomas in both legs. Marked thrombocytopenia
      (9000/microliters), haemolytic anaemia (lactate dehydrogenase 1800 U/l,
      haemoglobin 7.8 g/dl, haptoglobin 5 mg/dl) and skin haemorrhages suggested a
      second recurrence of TTP. The blood film showed a massive increase in fragmented
      cells (more than 30 per field), microspherocytes and normoblasts. Thrombocyte
      values initially rose on daily treatment with plasmapheresis using membrane
      separation and fresh plasma exchange. However, after two attempts at stopping
      therapy, plasmapheresis and fresh plasma replacement failed to normalise
      thrombocyte values. The patient had a total of 44 plasmaphereses. Intravenous
      administration of three doses of 1.5 mg vincristine at intervals of 7 and 5 days
      combined with further plasmapheresis treatment soon led to normalisation of the
      thrombocyte count (320,000/microliters), a fall in lactate dehydrogenase (120
      U/l) and a disappearance of fragment cells in the blood smear. The patient is
      still in complete remission 6 months after stopping treatment. Treatment with
      vincristine should be considered for TTP refractory to treatment.

PMID- 7712936
TI  - [Spontaneous bacterial peritonitis in liver cirrhosis with ascites].

PMID- 7712937
TI  - ["Accompanying hepatitis" in viral infections].

PMID- 7712938
TI  - [Fluctuating blood copper concentrations].

PMID- 7712939
TI  - [Endoscopic balloon dilatation of colonic stenosis].

PMID- 7712940
TI  - [Leukotriene in physiopathology of systemic mastocytosis].

PMID- 7712941
TI  - [The effect of donor and recipient ages on the results of kidney
      transplantation].
AB  - In a retrospective study of 814 patients (349 women, 465 men) who had received
      their first kidney transplant, early function rate as well as transplant and
      patient survival rates were determined in relation to age (up to 50 years: 530;
      51-55 years: 140; 56-60 years: 83; over 60 years: 61). The same rates were also
      grouped by donor age (> 16 years, 68 patients; 16-40 years, 387; 41-50 years,
      165; 51-60 years, 144; over 60 years, 50). The 5-year transplant function rate
      fell significantly with increasing donor age (P = 0.0001) from 78% (16-40 years)
      to 47% (over 60 years). For the same age groups the proportion of transplants
      which never resumed their function rose from 8 to 28%. Age of recipient had no
      influence on early function and 5-year transplant function rates. Thus,
      regardless of the recipient's age, higher donor age is an independent risk factor
      for early and late results after transplantation.

PMID- 7712942
TI  - [Percutaneous intraluminal ultrasound studies of the biliary tract in the
      diagnosis of malignant biliary obstruction].
AB  - The diagnostic value of percutaneous intraluminal ultrasound examination of the
      biliary tract (PIBUS) for the staging of malignancies that had obstructed the
      biliary tract was assessed in a prospective study. Intrabiliary sonography was
      performed 25 times in 22 patients (seven women, 15 men; mean age 66.4 +/- 16
      years) with obstructive jaundice in whom percutaneous transhepatic drainage of
      the biliary tract had been undertaken. The obstruction involved the hepatic duct
      bifurcation in 15 patients, the distal portion of the choledochal duct in five
      and its central portion as well as hepaticojejunostomy in one patient each.
      Ultrasound examination made it possible to assess tumour infiltration into the
      lumen of the biliary tract, its wall or its surrounding structures. Correct T
      staging was successful in all 12 patients with carcinoma of the biliary tract
      (T1: n = 4; T2: n = 2; T3: n = 6), judged against the "gold standard" of
      exploratory laparotomy in nine. Infiltration of the portal vein was demonstrated
      in three patients, lymph node metastases in the region of the hepatoduodenal
      ligament in seven. This experience indicates that PIBUS makes it possible
      correctly to T-stage carcinoma of the biliary tract, but because of its limited
      depth penetration it has to be combined with conventional imaging procedures for
      precise definition of the N and M stages.

PMID- 7712943
TI  - [Percutaneous endoscopic colopexy--a new treatment possibility for volvulus of
      the sigmoid].
AB  - An 83-year-old woman, largely bedridden since a stroke 2 years before, was
      hospitalized because of upper abdominal pain, nausea and obstipation. She had
      regularly been taking laxatives of the anthraquinone type. She had a fever of
      38.6 degrees C and leukocytosis (14,900/microliters). Radiological examination
      revealed volvulus of the sigmoid colon with ileus. As she vehemently refused an
      operation, it was attempted to reduce the volvulus endoscopically. At the first
      coloscopy the volvulus was untwisted. At that time there were already areas of
      necrosis in the rectosigmoid and descending sigmoid portions. As the volvulus
      recurred three days later, another coloscopic derotation was performed, this time
      with fixation of the sigmoid by three gastrostomy tubes for 20 days. The further
      course was uncomplicated, the patient had regular bowel movements and became free
      of fever and symptoms. The white cell count returned to normal and the intestinal
      mucosa healed histologically without scarring. There has been no recurrence for
      10 months. The conventional treatment of volvulus of the sigmoid is decompression
      followed by sigmoid resection. This case describes for the first time the
      nonoperative treatment by percutaneous endoscopic colopexy.

PMID- 7712945
TI  - [The metabolic syndrome].

PMID- 7712946
TI  - [Sepsis: a conception in change. Possibilities and limitations of diagnosis based
      on clinical criteria].

PMID- 7712944
TI  - [Therapy of chronic constipation].

PMID- 7712947
TI  - [Combination of low molecular weight heparin and dihydroergotamine for prevention
      of thrombosis].

PMID- 7712948
TI  - [Long term prognosis for the Y-prosthesis of the aortic bifurcation].

PMID- 7712949
TI  - [Incipient cervical myelopathy. Are there symptoms that point in that direction
      and a constellation of findings?].

PMID- 7712950
TI  - [Calcium carbonate intake: a possibility for long term osteoporosis prevention?].

PMID- 7712951
TI  - Behavioral states in the fetal baboon.
AB  - This study was designed to characterize behavioral states in the fetal baboon.
      Automated methods were developed and validated to recognize behavioral states
      based on relationships among three physiologic variables (EEG patterns, eye
      movements, heart period variability). Data included twelve 16-h records from 3
      chronically instrumented fetal baboons at 0.8-0.9 of term. Randomly generated
      control records were used to differentiate occurrences of state from chance
      association of the variables. For 41.2 +/- 4.6% (mean +/- S.E.) of the time, the
      physiologic variables were synchronous and formed cycles of state with a mean
      duration of 34.4 min. Components of these cycles had mean +/- S.E. durations of
      7.2 +/- 0.3 min for state 1FB (the analogue of quiet sleep in the human infant
      and state 1F in the human fetus), 20.7 +/- 1.2 min for the state 2FB (the
      analogue of active sleep in the human infant and state 2F in the human fetus),
      and 3.6 +/- 0.2 min for state transitions. For 24.6 +/- 2.4% of the time, the
      state variables exhibited coincidental, state-like agreements, that were not part
      of state cycles. Finally, for 34.3 +/- 2.7% of the time, there was no systematic
      agreement among the three variables. These data provide convincing evidence that
      organized behavioral states are present in the fetal baboon as early as 0.8 of
      term gestation.

PMID- 7712952
TI  - Vitamin A and related essential nutrients in cord blood: relationships with
      anthropometric measurements at birth.
AB  - Following the advice given by the Department of Health to women who are, or may
      become pregnant, not to eat liver and liver products because of the risk of
      vitamin A toxicity, the concentrations of vitamins A and E, and copper, magnesium
      and zinc in cord blood were investigated. The study was conducted in Hackney, an
      inner city area of London. Esters of vitamin A were not detected in any of the
      samples, indicating that there was no biochemical evidence of a risk of toxicity.
      Indeed, vitamin A correlated significantly with birthweight, head circumference,
      length, and gestation period. There was also a significant positive relationship
      between zinc and birthweight. In contrast, copper showed a negative correlation
      with birthweight and head circumference. Vitamin E and magnesium were not
      associated with any of the anthropometric measurements, although magnesium showed
      an increasing trend with birthweight. The data suggest that most of the mothers
      of the subjects studied may have been marginal with respect to vitamins A and E
      and zinc. In those with low birthweight babies. a higher intake would have
      improved their nutritional status and possibly the outcome of their pregnancy.
      For these low-income mothers, liver and liver products are the cheapest and the
      best source of vitamins A and E, haem iron, B vitamins and several other
      essential nutrients; hence the advice of the Department of Health may have been
      misplaced.

PMID- 7712953
TI  - Post-prandial effects in reactivity of forehead and mid-femoral skin blood flow
      and heart rate in neonates.
AB  - The effect of post-prandial period on the cutaneous vascular reactivity was
      studied in twelve full-term infants on their 3rd postnatal day. The differences
      in vasomotor reactions between the forehead and femoral skin were also
      investigated. Two 10-min control registrations about 30 and 90 min after feeding
      were followed by a registration of equal duration during thermal stimulation of
      the skin. The lower extremity of each infant was stimulated by warm and cool air
      currents (5 cycles/min) to induce periodic vasomotor changes. The fast Fourier
      transform was used to compute variability spectra for the recorded skin blood
      flow, heart rate and respiratory wave form signals. The skin blood flow became
      synchronised to the thermal stimulation in both skin regions. Neither the
      spontaneous nor synchronised oscillations of the skin blood flow differed
      significantly between femoral skin and forehead. The post-prandial time did not
      have any influence on this synchronisation. Heart rate variability was
      synchronised to the periodicity of thermal stimulation more 1.5 h after feeding
      than 0.5 h after feeding. Respiration was not affected. The results show that
      increasing post-prandial time has no influence on the synchronised oscillations
      of skin blood flow. However, it potentiates reactivity of heart rate to
      perturbations in the peripheral vasculature.

PMID- 7712954
TI  - Changes in the volume and performance of the left ventricle in the early neonatal
      period.
AB  - To evaluate the effect of changes in preload on left ventricular (LV)
      performance, we used echocardiography to measure end-diastolic dimension, end
      systolic dimension, and stroke volume in newborns at 2, 12, 24, and 120 h of age.
      The stroke volume was calculated by the pulsed Doppler technique. The stroke
      volume showed the highest level at 2 h of age. The size of the ductus arteriosus
      correlated with the stroke volume. These results indicated that the increase in
      stroke volume was related to the increase in LV preload due to the shunt flow
      volume through the patent ductus arteriosus. M-mode echocardiographic indexes
      such as end-diastolic dimension, LV end-diastolic volume, and LV ejection
      fraction did not show any significant changes from 2 to 120 h of age. We conclude
      that M-mode echocardiographic evaluation of LV performance is unreliable in the
      early neonatal period. Our data also provide a useful basis for the
      interpretation of abnormal left ventricular systolic function in the early
      neonatal period.

PMID- 7712956
TI  - Fetal urine production at different gestational ages: correlation to various
      compromised fetuses in utero.
AB  - To reveal which fetal life-threatening diseases significantly contribute to
      impairment of in-utero urine production and also to determine the gestational age
      at which time aberrant urine production becomes manifest, we observed 376
      compromised fetuses (subject group) at 21-42 weeks' gestation using
      ultrasonography. A total of 358 uncomplicated fetuses, aged 21-40 weeks, were
      separately chosen as a control group. Statistical differences in the urine
      production rate between subject- and control-group fetuses were analysed using
      the Grubbs-Smirnoff test at corresponding gestational ages. Significant decreases
      were evident in: bilateral renal agenesis (100%) at 21-23 weeks; bilateral
      infantile polycystic kidney (100%) at 21-28 weeks; bilateral multicystic kidney
      disease (100%) at 21-31 weeks; donor fetuses with twin transfusion syndrome (TTS)
      (100%) at 21-28 weeks; post-term fetuses (100%) at 42 weeks; bilateral
      hydronephrosis (60%) at 21-38 weeks; non-immunologic hydrops fetalis (42%) at 21
      35 weeks; intrauterine growth retardation (41%) at 29-40 weeks; and upper
      gastrointestinal tract obstruction (36%) at 30-38 weeks. Significant increases
      were noted in: recipient fetuses with TTS (100%) at 21-28 weeks, and unilateral
      hydronephrosis (36%) at 27-32 weeks. All indicate that urine production clearly
      delineates various fetal conditions in utero, in a closely disease-dependent
      relation to gestational age.

PMID- 7712955
TI  - Treadmill stepping in infants born prematurely.
AB  - Premature infants stepped on a treadmill as early as 1-month corrected age and
      they performed more coordinated alternate steps than their full-term peers.
      Twelve low-risk premature infants were observed at 1-, 6- and 9-months corrected
      age. The infants were supported on a treadmill for five 20-s trials at three
      speeds. The following data were analysed from the video records: (1) Leg postures
      in treadmill-moving and non-moving trials, (2) various parameters of limb
      position and movement during each step cycle, and (3) multiple anthropometric
      measures. Premature infants at all ages performed coordinated alternating steps
      which responded to changes in speed. The premature infants had more extended leg
      postures during non-stepping analysis than they did once the swing was initiated.
      Low-risk premature birth did not interfere with the neuromotor pathway.
      Experience out-of-utero may have facilitated stepping.

PMID- 7712957
TI  - Development of the human medial superior olivary nucleus: a morphometric study.
AB  - The development of the human medial superior olivary nucleus was studied in
      serial sections of 10 fetuses at 12-35 weeks of gestation (WG), an infant at 2
      months of age and an adult of 63 years using an electronic planimeter with a
      computer. Morphometric analysis suggested that the development of the human
      medial superior olivary nucleus accelerates between 16 and 21 WG in terms of
      columnar lengths and volumes, neuronal sizes and circularity ratios, while it
      matures gradually in terms of the amount of Nissl bodies.

PMID- 7712958
TI  - Twinning is associated with an increased risk of left-handedness and inverted
      writing hand posture.
AB  - Left-handedness and inverted handwriting postures are more frequent among birth
      stressed individuals. Because twinning is also associated with increased birth
      risk, 298 twins were compared to 1192 age and sex matched singletons. Both left
      handedness and inversion were significantly more common in twins, although other
      indexes of laterality were not affected.

PMID- 7712959
TI  - Fetal behaviour in uncomplicated pregnancies after 41 weeks of gestation.
AB  - The development of fetal behaviour and of fetal behavioural states (FBS) has been
      well defined in preterm and term fetuses. However, FBS have not yet been studied
      after term, although this is a potentially very dangerous period and clinical
      management is controversial. We investigated fetal behaviour in normal
      pregnancies after 41 weeks of gestation (287 days, menstrual age, GA) as compared
      to control term fetuses. Furthermore, we wanted to see if the findings might have
      consequences for clinical management. Twelve healthy women with GA between 289
      and 298 days participated. All pregnancies were reliably dated and at the time of
      the study, there was a normal amount of fluid. Twelve healthy women with GA 273
      287 days served as controls. All subjects underwent a behavioural study using
      cardiotocography to record the heart rate (CTG), and two ultrasound scanners to
      observe body and eye movements, as described previously. All fetuses in both
      groups clearly exhibited FBS 1F-4F which fitted the definitions of Nijhuis et al.
      The median percentage of FBS 3F and 4F ('awake states') increased significantly
      from 6% in the term group to 21.5% in the fetuses after 41 weeks (P = 0.014). FBS
      1F ('quiet sleep') and 2F ('active sleep') decreased from 92 to 78% (P = 0.014),
      mainly at the expense of FBS 2F which decreased from 78 to 58% (P = 0.002). This
      indicates increasing wakefulness in utero. The fetal heart rate patterns (FHRP)
      associated with FBS 3F and 4F were impressive. For example, in FBS 4F, the FHRP
      showed large amplitude, prolonged accelerations which fused into a sustained
      tachycardia with only short periods of return to the baseline, resembling
      tachycardia with decelerations. We conclude that in normal pregnancies after 41
      weeks, the development of the fetal central nervous system continues, resulting
      in an increasing percentage of 'fetal wakefulness'. The CTG-patterns that result
      from these behaviours can easily mimic fetal distress and one should be aware of
      this phenomenon. Whether behavioural studies can be used to distinguish 'normal'
      from 'abnormal' fetuses after term awaits further study.

PMID- 7712960
TI  - Observation of movements during sleep in ALTE (apparent life threatening event)
      and apnoeic infants--a pilot study.
AB  - Fourteen infants of 2 months or 6 months of age were video-recorded during
      polysomnography. Four were normal infants, five had a history of ALTE (apparent
      life threatening event) and five had repeated and prolonged apnoea during sleep.
      Two ALTE infants have been recorded at 2 months as well as at 6 months of age.
      Movements during sleep could be classified into general movements, isolated
      movements of the upper extremity, startles, head rotations, and trunk rotations.
      In the ALTE cases at 2 months of age, the motility was quantitatively not
      different from the control infants but was markedly reduced at 6 months of age.
      (All cases had their event before 8 weeks of age.) In contrast to these findings,
      infants with repeated apnoea did not show a clear change in the quantity of their
      movements. With the exception of one ALTE case at 2 months, all observed cases of
      ALTE and apnoeic infants showed an abnormal quality of their spontaneous
      movements during sleep. As reported in a previous study, all these cases had also
      been found moving abnormally during wakefulness. It is suggested that the
      abnormal motility is a sequelae of the event (ALTE or repeated apnoeas) with as a
      consequence, an impairment of neural functions.

PMID- 7712962
TI  - Development of grating acuity, letter acuity, and visual fields in small-for
      gestational-age preterm infants.
AB  - Visual acuity and visual field development were assessed longitudinally in 21
      preterm children who were born small-for-gestational-age (SGA) and in 51 preterm
      children who were appropriate-for-gestational-age (AGA). Grating acuity was
      tested binocularly at 0-1 month and monocularly at 4, 9, 12, 18, 24, 30, 36 and
      48 months corrected age, using Teller acuity cards. Visual fields were measured
      binocularly using kinetic perimetry at the same ages. Recognition (letter) acuity
      testing was attempted using the crowded HOTV test in all subjects who came in for
      testing at 36 and 48 months. Children in the SGA group were matched to children
      in the AGA group by gestational age (+/- 3 weeks) and type of perinatal medical
      complications. There were no significant differences in grating acuity or
      binocular visual field size between the SGA and AGA groups. 78% of acuity scores
      for individual SGA-AGA pairs fell within one octave of perfect agreement.
      Binocular visual field size for each SGA-AGA pair also showed good agreement.
      Fewer SGA than AGA subjects were able to perform recognition acuity testing, and
      those SGA subjects who were able to perform the test, showed consistently poorer
      recognition acuity than their AGA counterparts. Thus, being SGA does not pose an
      additional risk for the development of grating acuity or binocular visual field
      size over the first 4 years of life in preterm children. SGA preterm children may
      be at risk, however, for acuity deficits when acuity is measured with the more
      complex targets and the greater test distance used to measure recognition acuity.

PMID- 7712961
TI  - A case-control study of histological chorioamnionitis and neonatal infection.
AB  - The authors report a prospective study of the correlation between
      histopathological alterations in the placenta and the umbilical cord and neonatal
      infection in 223 newborns. The pathological studies were specifically concerned
      with the presence of infection as shown by a polymorphonuclear infiltrate at
      these sites. Inflammatory lesions were demonstrated in 26.9% of specimens and
      were highest in those with prolonged premature rupture of membranes and in the
      least mature placentas. Among the cases of histological chorioamnionitis, only
      23.3% of infants had documented infection. Neonatal infection was diagnosed in
      7.2% of the newborns and was 10 times more frequent in preterm newborns. Among
      the cases of infected newborns, 87.5% of placentas had histological
      chorioamnionitis. Pneumonia and septicemia were the most frequent conditions
      found among infected newborns. There was a strong correlation between
      histological chorioamnionitis and neonatal infection. The data obtained in this
      investigation suggest that histological chorioamnionitis is an important
      indicator of neonatal infection.

PMID- 7712963
TI  - Maternal smoking and tooth formation in the foetus. II. Tooth crown size in the
      permanent dentition.
AB  - Altogether 2159 pregnancies among black and white Americans in the Collaborative
      Perinatal Study and dental casts from their children at the age of 6-12 years
      were studied to determine the effect of maternal smoking on permanent tooth crown
      dimensions. A trend of reduction, similar to that observed in the deciduous
      second molars, was found in the permanent first molars and also in the mesio
      distal dimension of permanent incisors in relation to sex and race of the
      children and smoking habits of the mother. In terms of peak in their mitotic
      growth, the results can be interpreted to indicate a sensitive period of intra
      uterine development from the 24th to 28th gestational weeks. Comparisons of
      postnatal body size and differential correlation patterns in affected tooth
      dimensions with early postnatal body and head size between smokers and non
      smokers, suggests that maternal smoking during pregnancy may have an effect on
      basic growth of the head and body and/or the developmental process that impacts
      tooth development at some specific sensitive period also during the postnatal
      formation of these tooth crowns.

PMID- 7712964
TI  - Endoscopic therapy of biliary and pancreatic disorders in children.
AB  - Although many reports in the literature describe the use of endoscopic retrograde
      cholangiopancreatography (ERCP) in children, few mention the therapeutic
      application of the technique in treating pediatric patients with pancreatic or
      biliary pathology. We report here on our two-year experience, consisting of 42
      ERCPs conducted in 25 patients for a variety of pancreaticobiliary indications.
      Ages ranged from 22 months to 19 years. Five patients had normal studies; the
      remainder were diagnosed with a variety of pancreatic and or biliary anomalies.
      Seventeen patients had therapeutic interventions consisting of sphincterotomy (n
      = 12), dilation (n = 6), or stent placement (n = 9), with many of these
      procedures being done in combination. Five patients had mild complaints of
      abdominal pain or vomiting immediately after ERCP, but no major technical or
      medical complications were encountered. We find that therapeutic ERCP can be
      safely performed in children, but only by highly experienced endoscopists
      familiar with these specialized procedures.

PMID- 7712966
TI  - Prophylactic sclerotherapy for esophageal varices: long-term results of a
      prospective study.
AB  - Controlled trials of endoscopic sclerotherapy for the prevention of the first
      variceal hemorrhage have given controversial results. We continued a previously
      reported study and randomly assigned 141 patients with esophageal varices and no
      prior gastrointestinal bleeding to either prophylactic sclerotherapy (n = 70) or
      no treatment (n = 71). Sclerotherapy was performed until complete eradication of
      the varices was achieved; recurrent varices were treated with repeat
      sclerotherapy. The groups were well balanced in terms of demographic and clinical
      characteristics. Patients in both groups who bled from varices received
      sclerotherapy whenever possible. During a median follow-up of 56 months, variceal
      bleeding occurred in 7% in sclerotherapy patients and 44% of control patients (p
      < 0.01). In the sclerotherapy group 59% died, and in the control group 51%
      (n.s.). In both groups, the mortality rate increased with the severity of liver
      function impairment. Sclerotherapy was not found to improve survival in patients,
      irrespective of the etiology of cirrhosis (alcoholic or nonalcoholic) or variceal
      size (low-grade or high-grade). We conclude that sclerotherapy is a suitable
      method to reduce the occurrence of the first variceal hemorrhage, but it does not
      appear to have an effect on survival.

PMID- 7712965
TI  - The role of endoscopic retrograde cholangiopancreatography in cholestatic
      infants.
AB  - Conjugated hyperbilirubinemia in infants is a serious problem, and one that
      requires further investigation. Early differentiation between extrahepatic and
      intrahepatic causes of cholestasis is essential for the proper management of
      cholestasis in infancy. A successful outcome in patients with extrahepatic
      biliary atresia is significantly influenced by the age at which the Kasai
      procedure (hepatoportoenterostomy) is performed. However, extensive diagnostic
      workup may fail to distinguish definitively between intrahepatic and extrahepatic
      disease, and exploratory laparotomy and intraoperative cholangiography are
      sometimes necessary to exclude extrahepatic disease. In the last four years, 20
      cholestatic infants were referred to our center in whom no definite diagnosis was
      possible, despite thorough diagnostic evaluation. In an attempt to increase the
      accuracy of our diagnostic work-up, we performed ERCP during the anesthetic
      period planned for liver biopsy. We succeeded in performing ERCP in 18 children
      (90%); in five of them (28%), patent bile ducts were demonstrated, and
      unnecessary laparotomy could be avoided. In four patients (22.2%), a stricture of
      the common bile duct was seen, in three combined with a choledochal cyst. In two
      patients (11.1%), only the common bile duct and gallbladder were opacified. Five
      of seven patients in whom only the pancreatic duct was visualized had complete
      occlusion of the extrahepatic biliary ducts at surgery. The other two patients
      did not undergo surgery because initially no signs of extrahepatic obstruction
      were found in their biopsy. One of these patients deteriorated and needed a liver
      transplant one year later. This patient proved to have extrahepatic biliary
      atresia. No severe complications of ERCP were observed; only sporadically, a
      slight elevation of pancreatic enzymes was noted. We advocate this procedure in
      the workup of infants with unexplained conjugated hyperbilirubinemia. Anomalies
      in the biliary tree can be demonstrated, and when patent bile ducts are found,
      laparotomy can be avoided.

PMID- 7712967
TI  - Prophylactic sclerotherapy for esophageal varices in high-risk cirrhotic patients
      selected by endoscopic and hemodynamic criteria: a randomized, single-center
      controlled trial.
AB  - Controlled trials of sclerotherapy for the prevention of the first variceal
      hemorrhage in cirrhotics have given conflicting results, in spite of an initial
      positive controlled trial. We designed therefore a new study in which only 89 of
      396 investigated patients were randomized to sclerotherapy (44 patients) or a
      control group (45 patients). The admission criteria were: no history of variceal
      bleeding, the presence of high risk varies, i.e., varices of degrees III and IV
      with minivarices on the surface of them, and portal pressure over 16 mmHg.
      Sclerotherapy sessions were performed at 0, 7, 14, 21, and 28 days, until the
      varices were reduced in size and completely covered by fibrous tissue. Follow-up
      endoscopy was performed at four-month and thereafter at six-month intervals. The
      control patients underwent repeated clinical investigation and endoscopy at six
      month intervals. Bleeding episodes were treated by emergency endoscopic
      sclerotherapy in both groups, whenever possible. The mean follow-up was 33
      months. The results were analyzed using Student's t-test and the log-rank test.
      Variceal bleeding occured in 11 sclerotherapy patients (25%) and 34 controls
      (75.6%) (p < 0.05). The overall mortality was 25% (11 patients) among the
      sclerotherapy patients and 69% (31 patients) in the controls (p < 0.01).
      Prophylactic endoscopic sclerotherapy was able to prolong survival in Child-Pugh
      classes A and B, but not in C. It is concluded that prophylactic endoscopic
      sclerotherapy does reduce the incidence of first variceal bleeding in cirrhotic
      patients, and is able to prolong survival if only high-risk patients are selected
      and the treatment is performed by endoscopic experts.

PMID- 7712968
TI  - Endoscopic treatment of biliary leakage after laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy is an effective and safe treatment for uncomplicated
      symptomatic cholelithiasis. However, biliary tract injury may be more common with
      this procedure than with open cholecystectomy. We have encountered 17 patients
      with a biliary leak among 465 patients undergoing laparoscopic cholecystectomy,
      the diagnosis being established by clinical and radiographic parameters. The most
      common site of leakage was the cystic duct stump. Patients underwent endoscopic
      sphincterotomy and biliary stent placement, with an overall success rate of 96%.
      No morbidity or mortality related to the endoscopic procedures was encountered.
      We conclude that biliary leakage after laparoscopic cholecystectomy is uncommon.
      When it occurs, it can be treated safely and efficaciously by endoscopic means.

PMID- 7712969
TI  - Regional blood flow and reflux gastritis in the resected stomach.
AB  - Laser Doppler flowmetry (LDF) was used for endoscopic measurement of regional
      blood flow in 20 patients who had undergone previous gastric resection for peptic
      ulcer. Twenty-five patients with intact stomach and normal endoscopic findings
      were used as controls. In resected patients, the degree of enterogastric reflux
      gastritis was assessed by subjective grading and by morphological examination of
      biopsies from the region of the gastroenterostomy. In patients with an intact
      stomach, the average blood flow was significantly higher in the body of the
      stomach compared to the antrum (p < 0.001), without any significant differences
      between the greater and lesser curvature. In resected patients, the average blood
      flow in the gastric body remnant was markedly higher than in the region of the
      gastroenterostomy, but also significantly higher than the corresponding area of
      the gastric body in patients with an intact stomach (p < 0.01). The degree of
      gastritis in the region of the stoma of resected patients was often overestimated
      on subjective endoscopic assessments compared to morphological biopsy
      examinations. The degree of histological gastritis was not significantly
      correlated to blood flow levels of the gastroenterostomy. It is concluded that
      low gastric wall perfusion, impeding mucosal defense, does not seem to be a major
      factor in the development of enterogastric reflux gastritis in the resected
      stomach.

PMID- 7712970
TI  - Prophylaxis of first variceal bleeding: where does the truth lie.

PMID- 7712971
TI  - Endoscopic ultrasonography in chronic pancreatitis.

PMID- 7712972
TI  - Endoscopic management of spontaneous perforation of an intrahepatic bile duct.

PMID- 7712973
TI  - A simple endoscopic technique for replacement of a permanent malfunctioning
      gastrostomy.

PMID- 7712974
TI  - Duodenal metastases from lung cancer.

PMID- 7712975
TI  - Migrating surgical suture material in the duodenum after cholecystectomy.

PMID- 7712976
TI  - Laparoscopic fenestration for a giant liver cyst.

PMID- 7712977
TI  - Endoscopic removal of retained surgical gauze.

PMID- 7712978
TI  - Esophageal lichen planus.

PMID- 7712979
TI  - Successful endoscopic removal of part of a T-tube from the common bile duct.

PMID- 7712980
TI  - Proceedings of the 9th International Symposium on Endoscopic Ultrasonography.
      Bologna, Italy, November 28-29, 1993. Abstracts.

PMID- 7712981
TI  - The challenge of endoscopic ultrasonography.

PMID- 7712982
TI  - Endoscopic ultrasonography in the preoperative staging of esophageal cancer.
AB  - Endoscopic ultrasonography is the best available method for the locoregional
      staging of esophageal carcinoma. Its main limitations are represented by a) tumor
      stenosis, b) distinguishing between malignant and benign lymph nodes, and c)
      distinguishing between mucosal and submucosal cancer. In untreated esophageal
      carcinoma, three main groups can be distinguished, based on clinical and
      morphological evaluation (endoscopy, abdominal ultrasound and CT). EUS is not
      useful when palliative treatment aiming to relieve dysphagia is the only
      treatment. In tumors with a superficial pattern at endoscopy, EUS is necessary to
      distinguish T1 from more invasive tumors, but endoscopic treatment (photodynamic
      therapy, strip biopsy) is indicated only in nonsurgical patients. In the last,
      and largest, group of tumors with no clear surgical contraindication, EUS is
      necessary when surgery is not the only treatment considered. EUS staging then
      improves patient management (surgery alone, surgery with preoperative treatment,
      or nonsurgical treatment; type of surgery). Moreover, it provides a good
      evaluation of the prognosis, and allows better follow-up after nonsurgical
      treatment.

PMID- 7712983
TI  - Endoscopic ultrasonography for early gastric cancer.

PMID- 7712984
TI  - Response to chemotherapy in esophageal cancer.

PMID- 7712985
TI  - The role of endoscopic ultrasonography in monitoring treatment: response to
      chemotherapy in lymphoma.

PMID- 7712986
TI  - Anastomotic recurrence in upper gastrointestinal cancer.

PMID- 7712987
TI  - Endoscopic ultrasonography of perigastrointestinal lymph nodes.
AB  - The introduction of endoscopic ultrasonography (EUS) has opened a window in the
      diagnosis of the perigastrointestinal lymph nodes. Initial euphoria has been
      sobered by the fact that false-positive and false-negative diagnoses may occur.
      We review here the use of EUS to stage gastrointestinal cancer, and particularly
      to predict the presence or absence of lymph-node metastases. The role of EUS
      guided fine-needle aspiration using a radial scanner or a curved array
      echoendoscope is mentioned.

PMID- 7712988
TI  - Endoscopic ultrasonography-guided fine-needle aspiration biopsy of lymph nodes.
AB  - The recent introduction of convex linear array echoendoscopes equipped with a
      biopsy channel has made fine-needle aspiration biopsy (FNAB) under direct
      endosonographic guidance possible. Because the imaging and instrumentation planes
      overlap, the operator can visualize a biopsy needle lengthwise as it enters the
      sector-shaped sound field. We performed EUS-guided FNAB of lymph nodes in seven
      patients who met the following criteria: (1) Lymph node size over > 1 cm; (2) no
      endoscopic or endosonographic evidence for tumor involvement of bowel wall
      interposed between the lymph node and the transducer; and (3) absence of
      coagulopathy or thrombocytopenia. A positive tissue yield was obtained in six
      patients, of whom five had malignant cells identified on cytology. The patient
      with an inadequate yield had a dry aspirate, possibly related to prior
      irradiation treatment for esophageal carcinoma. No procedure-related
      complications were observed. We conclude that EUS-guided FNAB of lymph nodes is
      technically feasible, provides a high diagnostic yield, and appears to be safe.
      Further studies to determine the sensitivity and specificity of this novel
      procedure are warranted.

PMID- 7712989
TI  - Endoscopic ultrasound versus computed tomography in the evaluation of the
      mediastinum in patients with non-small-cell lung cancer.

PMID- 7712990
TI  - Endoscopic ultrasonography in the diagnosis of submucosal tumors: need for
      biopsy.

PMID- 7712991
TI  - Endoscopic ultrasonography in achalasia.

PMID- 7712992
TI  - Endoscopy versus endoscopic ultrasonography in staging reflux esophagitis.
AB  - Precise staging of reflux esophagitis is very important for therapeutic
      decisions; in fact, chronic gastroesophageal reflux may cause transmural
      inflammation that leads to fibrosis with loss of esophageal wall compliance. In
      reflux esophagitis, endoscopic stating is limited to mucosal injury, while
      endoscopic ultrasonography (EUS) is able to visualize changes in the layer
      structure and localized or diffuse thickenings of the esophageal wall. In order
      to evaluate the usefulness of EUS in reflux esophagitis, a prospective study of
      31 patients and ten normal subjects was performed. Endoscopic reflux esophagitis
      was staged as: E1 (erythema, n = 7), E2 (erosions, n = 13), E3 (ulcers, n = 11).
      EUS findings were recorded and evaluated at five different levels, starting from
      the gastroesophageal junction, using a quantitative method, the center line
      method. With this method, the sectorial and mean thickness, and area were
      calculated for each level. There was a significant difference between patients
      with reflux esophagitis and normal subjects in our study. E3 patients showed a
      significant upward involvement of the wall far from the visible lesions. Mild
      esophagitis may also cause esophageal wall thickening, involving even the entire
      wall. There was no correlation between the onset time of symptoms and the degree
      of thickening. In conclusion, EUS seems to be an important supplement to
      endoscopy in staging reflux esophagitis, as the progression of the inflammation
      is not related to the endoscopic findings.

PMID- 7712993
TI  - Evaluating gastric ulcer healing by endoscopic ultrasonography.

PMID- 7712994
TI  - The role of endoscopic ultrasonography in biliary tract disease: obstructive
      jaundice.
AB  - Forty-one patients (22 females, 19 males, mean age 74 years, range 41-93) with
      extrahepatic obstructive jaundice were evaluated by transcutaneous sonography
      (US), endoscopic ultrasonography (EUS), and endoscopic retrograde
      cholangiopancreatography (ERCP) within 24 hours of hospital admission. EUS was
      always performed after US and immediately prior to ERCP, the latter being
      considered the "gold standard" for this study. EUS findings were documented
      according to a pre-set data protocol in a blind fashion with respect to ERCP
      results. Common bile duct (CBD) dilatation was demonstrated by all three methods.
      Stones in the distal CBD causing obstruction were demonstrated by EUS in 15 out
      of 16 patients, but in only seven cases by US. In 25 patients, the underlying
      malignant disease was identified by EUS as well as ERCP, and the level of biliary
      obstruction was correctly determined by both methods, while with US this was
      possible only in 17 (89%) and 20 (80%) cases, respectively. In comparison with
      ERCP, EUS provided a direct image of the tumor and allowed for regional staging
      in all patients. EUS was superior to US in elucidating the cause of biliary
      obstruction. EUS provides an additional means to decide quickly on appropriate
      therapy. At present, a shortcoming of the method is that no therapeutic
      interventions can be performed during EUS examination.

PMID- 7712995
TI  - The role of endoscopic ultrasonography in the biliary tract: ampullary tumors.

PMID- 7712996
TI  - Endoscopic ultrasonography in pancreatic cancer.

PMID- 7712997
TI  - Endoscopic ultrasonography in chronic pancreatitis.

PMID- 7712998
TI  - Preoperative staging of rectal and colonic cancer.
AB  - In rectal cancer, endosonography assesses the tumor penetration depth, EUS T1 to
      EUS T3, with a sensitivity of 96% and a specificity of 89%. The evaluation of
      lymph nodes is less accurate, at 79%. The surgical strategy is different in the
      three parts of the rectum, and depends on the endosonographic tumor stage: upper
      third of the rectum--anterior resection for all tumor stages; middle third of the
      rectum--EUS T1 N0: transanal endoscopic microsurgery for "low-risk" carcinomas;
      EUS T1-2: anterior resection; EUS T3: anterior resection with complete excision
      of the mesorectum, reconstruction with coloanal pouch; lower third of the rectum-
      EUS T1 N0: transanal endoscopic microsurgery for "low-risk" carcinomas; EUS T1-2:
      anterior or intersphincteric resection with complete excision of the mesorectum,
      reconstruction with colon pouch; EUS T3: abdominoperineal excision. With the
      impact of endosonography, the proportion of abdominoperineal excisions has
      dropped from 46% to 15% during the last five years. Laparoscopic technology is
      likely to have an increasing impact on surgical procedures that have previously
      required an open approach. The following treatment policy derived from the
      endosonographic staging of colon tumors is proposed: EUS T1, laparoscopic
      segmental resection; EUS T2, laparoscopic oncological resection; EUS T3,
      conventional open surgery.

PMID- 7713000
TI  - Development and clinical use of ultrasonic probes.

PMID- 7712999
TI  - Endoscopic ultrasonography of perianorectal fistulas and abscesses.
AB  - In this article we describe the history, instrument, indications, and results of
      endoscopic ultrasonography (EUS) in the evaluation of perianorectal fistulas and
      abscesses. EUS has been reported to be helpful in the management of patients with
      Crohn's disease or colitis associated with fistulas and abscesses, due to its
      clear imaging of the leasion and valuable topographic anatomical information.
      Recent studies point out the relationship between EUS and electromyography. We
      believe EUS will become a standard procedure in the management of these complex
      disease processes.

PMID- 7713003
TI  - A matter of nomenclature.

PMID- 7713002
TI  - Why is grass green?

PMID- 7713001
TI  - Endoscopic ultrasonography with the ultrasonic esophagoprobe.
AB  - Forty-one patients with either stenosing esophageal and cardia carcinoma (n = 27)
      or suspected tumor stenosis (n = 14), in whom conventional endosonography had
      failed, were evaluated with the ultrasonic esophagoprobe (blind probe). The main
      indication was locoregional staging of esophageal and cardia carcinomas, or
      restaging after radiotherapy or combined chemotherapy and radiotherapy. In 37% of
      the patients (10 of 27) an EUS T4 carcinoma was diagnosed, and in 63% (17/27) an
      EUS-T3 one. Regional lymph-node metastases were diagnosed in 96% of the cases.
      EUS restaging after nonsurgical palliative treatment detected tumor lesions in
      three of eight patients. Despite the fact that the imaging quality is still not
      satisfactory, our results suggest that the limitations of endoscopic
      ultrasonography (EUS) examination due to stenosing tumor growth can be overcome
      by the use of this ultrasonic esophagoprobe or similar instruments. Further
      technical developments may improve the resolution as well as the imaging quality
      in the celiac axis region.

PMID- 7713004
TI  - Another look at bovine growth hormone.

PMID- 7713005
TI  - Controlling malaria.

PMID- 7713006
TI  - EMFs: breast cancer culprits?

PMID- 7713007
TI  - Tree of life.

PMID- 7713008
TI  - Asthma gene is nothing to sneeze at.

PMID- 7713009
TI  - ER gene disruption is a knockout.

PMID- 7713010
TI  - Solutions from the sea.

PMID- 7713012
TI  - Mechanism-based toxicology.

PMID- 7713011
TI  - Cyanide exposure may affect the brain.

PMID- 7713013
TI  - A continent in chaos: Africa's environmental issues.

PMID- 7713014
TI  - The price of progress: environmental health in Latin America.

PMID- 7713015
TI  - Environmental health: the global report card, 1994.

PMID- 7713016
TI  - p53 in 3-D.

PMID- 7713018
TI  - Intestinal absorption of dietary cadmium in women depends on body iron stores and
      fiber intake.
AB  - Measurements of intake and uptake of cadmium in relation to diet composition were
      carried out in 57 nonsmoking women, 20-50 years of age. A vegetarian/high-fiber
      diet and a mixed-diet group were constructed based on results from a food
      frequency questionnaire. Duplicate diets and the corresponding feces were
      collected during 4 consecutive days in parallel with dietary recording of type
      and amount of food ingested for determination of the dietary intake of cadmium
      and various nutrients. Blood and 24-hr urine samples were collected for
      determination of cadmium, hemoglobin, ferritin, and zinc. There were no
      differences in the intake of nutrients between the mixed-diet and the high-fiber
      diet groups, except for a significantly higher intake of fiber (p < 0.001) and
      cadmium (p < 0.002) in the high-fiber group. Fecal cadmium corresponded to 98% in
      the mixed-diet group and 100% in the high-fiber diet group. No differences in
      blood cadmium (BCd) or urinary cadmium (UCd) between groups could be detected.
      There was a tendency toward higher BCd and UCd concentrations with increasing
      fiber intake; however, the concentrations were not statistically significant at
      the 5% level, indicating an inhibitory effect of fiber on the gastrointestinal
      absorption of cadmium. Sixty-seven percent of the women had serum ferritin < 30
      micrograms/l, indicating reduced body iron stores, which were highly associated
      with higher BCd (irrespective of fiber intake). BCd was mainly correlated with
      UCd, serum ferritin, age, anf fibre intake. UCd and serum ferritin explained
      almost 60% of the variation in BCd.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713017
TI  - Asbestos and colon cancer: a weight-of-the-evidence review.
AB  - What is the evidence that exposure to asbestos causes colon cancer? This weight
      of-evidence review considers epidemiologic evidence from cohort studies of
      asbestos-exposed workers, case-control studies of colon cancer, animal bioassays,
      and other corroborative evidence. The major evidence for a causal association at
      high exposure is a combined colorectal standardized mortality ratio (SMR) of 1.5
      for asbestos cohorts where the lung cancer SMR was greater than twofold. However,
      misdiagnosis may spuriously elevate the SMR. The strongest evidence against a
      causal association between colon cancer and asbestos exposure is the lack of an
      exposure-response gradient in asbestos cohorts where trends for lung cancer are
      observed. Population-based case-control studies of colon cancer do not show any
      consistent risk associated with asbestos exposure. Long-term ingestion studies
      show no evidence of an increased incidence of colon cancer in animals by this
      route of exposure and do not provide biological plausibility for a causal
      association between asbestos exposure and colon cancer.

PMID- 7713020
TI  - Human nasal mucosal changes after exposure to urban pollution.
AB  - Millions of people worldwide are living in areas where ozone (O3) concentrations
      exceed health standards (an hourly average of 235 micrograms/m3/0.12 ppm, not to
      be exceeded more than once per year). Ozone induces acute nasal inflammatory
      responses and significant epithelial lesions in experimental animals and humans.
      To determine the nasal effects of a 15-day exposure to an urban polluted
      atmosphere with O3 as the main pollutant, we studied a population of healthy,
      young males newly arrived to southwest metropolitan Mexico City (SWMMC). The
      study included 49 non-smoking residents in an unpolluted port, Veracruz City; 14
      subjects stayed in the port and served as controls, while 35 subjects traveled to
      SWMMC and had serial nasal lavages at different times after arriving in SWMMC.
      Subjects had exposures to ambient O3 an average of 10.2 hr/day, with a total
      cumulative O3 exposure of 10.644 ppm.hr. Nasal inflammatory responses,
      polymorphonuclear leukocyte PMN-CD11b surface expression, rhinoscopic changes,
      and respiratory symptoms were evaluated. Exposed subjects had massive nasal
      epithelial shedding and significant responses in PMN nasal influx (p < 0.00001)
      and in PMN-CD11b expression (p < 0.05). Cumulative O3 exposure correlated with
      respiratory symptoms, PMNs (rs = 0.2374, p < 0.01), and CD11b (rs = 0.3094, p <
      0.01); 94% of exposed subjects experienced respiratory symptoms, and 97% left the
      city with an abnormal nasal mucosa by rhinoscopy. Nasal epithelial changes
      persisted 2 weeks after the exposed subjects returned to their nonpolluted
      environment. Exposure to an urban polluted atmosphere induces significant and
      persistent nasal epithelial alterations in healthy subjects.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7713023
TI  - Napa Conference on Genetic and Molecular Ecotoxicology. October 12-15, 1993,
      Yountville, California. Proceedings.

PMID- 7713019
TI  - Modulation of bronchial epithelial cell barrier function by in vitro ozone
      exposure.
AB  - The epithelial cells lining the small, peripheral airways function as important
      targets for the action of inspired ozone. Loss of epithelial barrier integrity in
      these regions is a common element in ozone-induced airway inflammation. To
      investigate the direct effect of ozone on epithelial barrier function, canine
      bronchial epithelial (CBE) cells grown with an air interface were exposed for 3
      hr to 0.2, 0.5, or 0.8 ppm ozone or to air. Mannitol flux, used as an index of
      paracellular permeability, increased above air controls by 461%, 774%, and 1172%
      at the three ozone concentrations, respectively. Transcellular electrical
      resistance exhibited a dose-related decrease. The immediate effect of 0.8 ppm
      ozone on permeability was significantly inhibited by preincubation for 48 hr in
      the presence of 1 ng/ml vitamin E (33%) or 1 microM vitamin A (34%). Responses to
      0.5 ppm or 0.8 ppm were inhibited by pretreatment of the cells with 0.1 microM of
      the actin polymerizing agent phalloidin (34% and 25% inhibition, respectively).
      The increases in permeability induced by 0.2 and 0.5 ppm ozone were attenuated by
      54% and 22%, respectively, at 18 hr after exposure, whereas that to 0.8 ppm was
      further enhanced by 42% at this time. The effects of ozone are modulated by the
      availability of antioxidants to the cells and appear to be associated with
      cytoskeletal dysfunction in CBE cells. The data are consistent with a loss of
      barrier function linked to a direct oxidative effect of ozone on individual CBE
      cells and indicate that the reversible or progressive nature of this effect is
      dose dependent.

PMID- 7713021
TI  - Evaluation of dermal and respiratory chloroform exposure in humans.
AB  - Chloroform is a known contaminant of chlorinated drinking water and of swimming
      pool water disinfected with chlorine or one of its derivatives. Few data exist
      regarding the importance of dermal and inhalation exposure routes to the
      chloroform body burden resulting from domestic and recreational use of
      chlorinated water. In our experimental study involving 11 male swimmers, we
      quantified the body burden resulting from exposure to various concentrations of
      chloroform in water and air of an indoor swimming pool, during a daily 55-min
      exercise period. From the first to the sixth exercise period, CHCl3 mean
      concentration in water was increased from 159 micrograms/l to 553 micrograms/l.
      Corresponding mean air CHCl3 level ranged from 597 ppb to 1630 ppb. To dissociate
      the dermal exposure route from that of inhalation, swimmers used scuba tanks
      during an additional exercise period. Chloroform concentrations were measured in
      alveolar air before and after each exercise period, as well as after 35 min of
      physical activity. Chloroform levels in water and air were measured every 10 min.
      We examined the relationship between alveolar air concentration (a measure of
      body burden) at 35 and 55 min and environmental chloroform concentrations by
      using multiple regression models. The natural logarithm of alveolar air
      concentration was strongly correlated with aqueous chloroform concentration both
      at 35 (p2 < 0.001, r2 = 0.75) and 55 min (p < 0.001, r2 = 0.86). The relationship
      with air concentrations was also statistically significant (35 min: p < 0.001, r2
      = 0.58, 55 min: p < 0.001, r2 = 0.63).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713022
TI  - Evaluating health risks from occupational exposure to pesticides and the
      regulatory response.
AB  - In this study, we used measurements of occupational exposures to pesticides in
      agriculture to evaluate health risks and analyzed how the federal regulatory
      program is addressing these risks. Dose estimates developed by the State of
      California from measured occupational exposures to 41 pesticides were compared to
      standard indices of acute toxicity (LD50) and chronic effects (reference dose).
      Lifetime cancer risks were estimated using cancer potencies. Estimated absorbed
      daily doses for mixers, loaders, and applicators of pesticides ranged from less
      than 0.0001% to 48% of the estimated human LD50 values, and doses for 10 of 40
      pesticides exceeded 1% of the estimated human LD50 values. Estimated lifetime
      absorbed daily doses ranged from 0.1% to 114,000% of the reference doses
      developed by the U.S. Environmental Protection Agency, and doses for 13 of 25
      pesticides were above them. Lifetime cancer risks ranged from 1 per million to
      1700 per million, and estimates for 12 of 13 pesticides were above 1 per million.
      Similar results were obtained for field workers and flaggers. For the pesticides
      examined, exposures pose greater risks of chronic effects than acute effects.
      Exposure reduction measures, including use of closed mixing systems and personal
      protective equipment, significantly reduced exposures. Proposed regulations rely
      primarily on requirements for personal protective equipment and use restrictions
      to protect workers. Chronic health risks are not considered in setting these
      requirements. Reviews of pesticides by the federal pesticide regulatory program
      have had little effect on occupational risks. Policy strategies that offer
      immediate protection for workers and that are not dependent on extensive review
      of individual pesticides should be pursued.

PMID- 7713024
TI  - Genotypic toxicity: implications for individuals and populations.
AB  - The goals of genetic ecotoxicology are discussed and redefined. New directions in
      which genotoxicity "effect" studies might be pursued are outlined. Recognition of
      the genotoxic disease syndrome in lower animals suggests that more attention
      should be given to exploring the relationships between DNA damage (adduct
      formation, gene mutations, etc.) and its manifestation at the level of
      individuals. Within a given population, not all individuals are equally
      susceptible to pollutant toxicity (including genotoxicity). It is proposed
      therefore, that more attention be paid to identifying the factors underlying
      interindividual variability in susceptibility. Examples are provided of specific
      cases in which differences in susceptibility to pollutants have been directly
      related to genotypic predisposition. This approach is also advocated for
      investigating the individual and population level consequences of genotoxic
      damage. The possibility of using phenotypic traits to recognise subsets of
      individuals within populations possessing similar genotypes is discussed.

PMID- 7713025
TI  - Adaptation to metals in widespread and endemic plants.
AB  - Bryophytes, including the mosses, liverworts, and hornworts, occur in a variety
      of habitats with high concentrations of metals and have other characteristics
      that are advantageous for studies of metal tolerance. Mosses may evolve
      genetically specialized, metal-tolerant races less frequently than flowering
      plants. Some species of mosses appear to have inherently high levels of metal
      tolerance even in individuals that have not been subjected to natural selection
      in contaminated environments. Scopelophila cataractae, one of the so-called
      copper mosses, not only tolerates extremely high concentrations of metals in its
      substrates, but requires these substrates for optimum growth. This species should
      be included in mechanistic studies of tolerance at the cellular and molecular
      levels.

PMID- 7713026
TI  - Environmental genotoxicity: probing the underlying mechanisms.
AB  - Environmental pollution is a complex issue because of the diversity of
      anthropogenic agents, both chemical and physical, that have been detected and
      catalogued. The consequences to biota from exposure to genotoxic agents present
      an additional problem because of the potential for these agents to produce
      adverse change at the cellular and organismal levels. Past studies in genetic
      toxicology at the Oak Ridge National Laboratory have focused on structural damage
      to the DNA of environmental species that may occur after exposure to genotoxic
      agents and the use of this information to document exposure and to monitor
      remediation. In an effort to predict effects at the population, community, and
      ecosystem levels, current studies in genetic ecotoxicology are attempting to
      characterize the biologic mechanisms at the gene level that regulate and limit
      the response of an individual organism to genotoxic factors in their environment.

PMID- 7713027
TI  - Molecular epizootiology: assessment of exposure to genotoxic compounds in
      teleosts.
AB  - The recent development of techniques to measure levels of carcinogens covalently
      bound to DNA provides the opportunity to use DNA adducts as molecular dosimeters
      of exposure to environmental carcinogens and mutagens. This is especially
      important because epizootiologic studies have shown a positive association
      between environmental carcinogens, such as polycyclic aromatic hydrocarbons, and
      increased prevalence of neoplasms and related lesions, primarily in liver, of
      benthic fish species from a wide range of urban and industrialized areas. In
      studies with wild fish and mammalian species the 32P-postlabeling assay, as
      developed for aromatic compounds, has been used most extensively because of its
      high sensitivity and ability to detect structurally uncharacterized adducts. The
      results to date of field and laboratory studies show that hepatic DNA adducts
      detected in fish are associated with increased exposure to environmental
      polycyclic aromatic compounds in the preponderance of species examined, whereas
      in the limited studies with wild mammals, such a relationship is equivocal at
      present. The findings with fish suggest that DNA adducts, as measured by 32P
      postlabeling, have the potential to be effective molecular dosimeters of exposure
      to environmental carcinogenic aromatic compounds and thereby may lead to an
      improved understanding of the etiology of neoplasia in wild teleosts.

PMID- 7713028
TI  - Somatic and heritable effects of environmental genotoxins and the emergence of
      evolutionary toxicology.
AB  - The genetic effects of environmental pollutants include mutations in somatic
      cells or germinal cells that are the direct result of exposure to toxicants.
      Biomarkers that detect such mutagenic effects have been developed and tested in
      field studies on wildlife populations. However, another class of genetic effects
      resulting from pollution exposure exists. Specifically, changes in allele
      frequencies of populations will occur as a result of population bottlenecks,
      inbreeding, or selection at loci critical for survival in polluted environments.
      We describe how such genetic alterations can be studied at the population level
      using the techniques of molecular genetics, and we predict the development of a
      new field, evolutionary toxicology, that will address such issues.

PMID- 7713029
TI  - Large-scale genotoxicity assessments in the marine environment.
AB  - There are a number of techniques for detecting genotoxicity in the marine
      environment, and many are applicable to large-scale field assessments. Certain
      tests can be used to evaluate responses in target organisms in situ while others
      utilize surrogate organisms exposed to field samples in short-term laboratory
      bioassays. Genotoxicity endpoints appear distinct from traditional toxicity
      endpoints, but some have chemical or ecotoxicologic correlates. One versatile end
      point, the frequency of anaphase aberrations, has been used in several large
      marine assessments to evaluate genotoxicity in the New York Bight, in sediment
      from San Francisco Bay, and following the Exxon Valdez oil spill.

PMID- 7713031
TI  - The Japanese medaka, Oryzias latipes, as a new model organism for studying
      environmental germ-cell mutagenesis.
AB  - The effects of genotoxic substances on ecosystems should be assessed using
      various test systems with multiple genetic end points. The most widely used test
      system has been the specific-locus test developed by W.L. Russell, using the
      mouse. We are developing a new, nonmammalian test system using the Japanese
      medaka, Oryzias latipes. We have examined 625,926 embryos that correspond to
      1,586,649 loci. In the medaka test system, four genetic end points are evaluated:
      dominant lethals, total mutations, viable mutations, and malformations. Because
      the medaka is an oviparous experimental animal, we were able to determine that
      approximately 90% of spontaneous as well as gamma-ray-induced total mutants died
      during development, irrespective of spermatogenesis stages at the time of
      exposure. Exposure of sperm and spermatids to ethylnitrosourea (ENU) also
      resulted in embryonic death of approximately 90% of total mutants. In sharp
      contrast, approximately 90% of total mutants recovered from ENU-exposed
      spermatogonia became viable mutants. These results indicate that the quantitative
      relationship between induction of specific-locus mutations and dominant lethals
      remains the same among spermatogenesis stages for gamma-rays, while it is biased
      excessively to the induction of specific-locus mutations in ENU-exposed
      spermatogonia. Thus, the assessment should integrate at least two factors, agent
      specific and species-specific effects.

PMID- 7713030
TI  - Genetic and molecular ecotoxicology: a research framework.
AB  - Participants at the Napa Conference on Genetic and Molecular Ecotoxicology
      assessed the status of this field in light of heightened concerns about the
      genetic effects of exposure to hazardous substances and recent advancements in
      our capabilities to measure those effects. We present here a synthesis of the
      ideas discussed throughout the conference, including definitions of important
      concepts in the field and critical research needs and opportunities. While there
      were many opinions expressed on these topics, there was general agreement that
      there are substantive new opportunities to improve the impact of genetic and
      molecular ecotoxicology on prediction of sublethal effects of exposure to
      hazardous substances. Future studies should emphasize integration of genetic
      ecotoxicology, ecological genetics, and molecular biology and should be directed
      toward improving our understanding of the ecological implications of genotoxic
      responses. Ecological implications may be assessed at either the population or
      ecosystem level; however, a population-level focus may be most pragmatic. Recent
      technical advancements in measuring genetic and molecular responses to toxicant
      exposure will spur rapid progress. These new techniques have considerable promise
      for increasing our understanding of both mechanisms of toxicity on genes or gene
      products and the relevance of detrimental effects to individual fitness.

PMID- 7713032
TI  - Molecular responses as indicators of marine pollution: DNA damage and enzyme
      induction in Limanda limanda and Asterias rubens.
AB  - During a survey from 26 August through 13 September 1991, specimens of the
      flatfish, Limanda limanda (dab), and the asteroid echinoderm Asterias rubens
      (seastar), were collected at sampling locations along transects radiating into
      the North Sea from the coastal zone of The Netherlands. In homogenates of liver
      tissue from male dab and the digestive gland (pyloric caeca) of female seastar,
      DNA damage (strand breaks) and induction of the cytochrome P450-dependent
      monooxygenase system (MO) were determined. Areas could be described with
      significantly increased percentages of strand breaks (lower integrity) both in
      dab and seastar. However, enhanced DNA strand breaks did not correspond with
      contamination gradients, expressed as concentrations of polychlorinated biphenyls
      (PCBs) or polyaromatic hydrocarbons. MO enzyme induction in the hepatic 13,000g
      fraction of male dab, measured as 7-ethoxyresorufin-O-deethylase activity, was
      significantly enhanced in response to low ambient temperatures. Some evidence was
      found for the facilitation of benzo[a]pyrene hydroxylase activity expressing the
      enzyme induction in the microsomal fraction of pyloric caeca of seastars, at
      increasing PCB concentrations. DNA integrity and enzyme induction elucidate the
      physiologic status and might be indicative for ambient impairment within
      restricted areas, and not necessarily related to the presence of anthropogenic or
      xenobiotic substances.

PMID- 7713033
TI  - Pollutant effects on the microbial ecosystem.
AB  - Genetic diversity of a microbial community will inevitably be affected by
      environmental stress. However, our understanding of the implications of these
      effects is limited. Genetic exchange between natural microbial communities
      appears to be a common phenomenon, mediated by a number of microbial processes
      (conjugation, transformation, and transduction). These mechanisms of change are
      presumably adaptations to natural environmental perturbation, e.g., the low
      levels of antibiotics produced by other organisms. However, anthropogenic
      influences on the environment may be accelerating genetic change within
      microbiologic ecosystems, beyond these natural adaptation rates. This article
      highlights some of the perceived risks to ecosystem health and research questions
      that need to be addressed.

PMID- 7713034
TI  - Nondestructive biomarkers in ecotoxicology.
AB  - The aim of this article is to attempt a concise review of the state of the art of
      the nondestructive biomarkers approach in vertebrates, establishing a consensus
      on the most useful and sensitive nondestructive biomarker techniques, and
      proposing research priorities for the development and validation of this
      promising methodology. The following topics are discussed: the advantages of the
      use of nondestructive strategies in biomonitoring programs and the research
      fields in which nondestructive biomarkers can be applied; the biological
      materials suitable for nondestructive biomarkers and residue analysis in
      vertebrates; which biomarkers lend themselves to noninvasive techniques; and the
      validation and implementation strategy of the nondestructive biomarker approach.
      Examples of applications of this methodology in the hazard assessment of
      endangered species are also presented.

PMID- 7713036
TI  - Considerations for evaluating ultraviolet radiation-induced genetic damage
      relative to Antarctic ozone depletion.
AB  - Springtime ozone depletion over the Antarctic results in increased UVB in local
      marine environments. It has been established that decreases in primary
      productivity occur with decreases in ozone concentrations, but the impact of
      increased UVB on the functioning and stability of the ecosystem has not yet been
      determined. Very little has been done to evaluate the potential for genetic
      damage caused by the increase in UVB, and this type of damage is most significant
      relative to the fitness and maintenance of populations. An essential problem in
      evaluating genotoxic effects is the lack of appropriate techniques to sample and
      quantify genetic damage in field populations under ambient UVB levels. In
      addition, it is currently not feasible to estimate exposure levels for organisms
      in their natural habitats.

PMID- 7713038
TI  - Genetic information and ecosystem health: arguments for the application of chaos
      theory to identify boundary conditions for ecosystem management.
AB  - To meet the demands for goods and services of an exponentially growing human
      population, global ecosystems will come under increasing human management. The
      hallmark of successful ecosystem management will be long-term ecosystem
      stability. Ecosystems and the genetic information and processes which underlie
      interactions of organisms with the environment in populations and communities
      exhibit behaviors which have nonlinear characteristics. Nonlinear mathematical
      formulations describing deterministic chaos have been used successfully to model
      such systems in physics, chemistry, economics, physiology, and epidemiology. This
      approach can be extended to ecotoxicology and can be used to investigate how
      changes in genetic information determine the behavior of populations and
      communities. This article seeks to provide the arguments for such an approach and
      to give initial direction to the search for the boundary conditions within which
      lies ecosystem stability. The identification of a theoretical framework for
      ecotoxicology and the parameters which drive the underlying model is a critical
      component in the formulation of a prioritized research agenda and appropriate
      ecosystem management policy and regulation.

PMID- 7713037
TI  - Toxicological foundations of ecological risk assessment: biomarker development
      and interpretation based on laboratory and wildlife species.
AB  - Ecological risk assessments based on chemical residue analysis and species
      demographics tend to ignore the bioavailability and bioaccumulation of the
      chemicals of concern. This study describes the incorporation of mechanistically
      based biomarkers into an ecological risk assessment of a poly-cyclic aromatic
      hydrocarbon (PAH)-contaminated site. A combination of soil residue analysis,
      tissue residue analysis, biomarkers in one-site trapped animals and biomarkers in
      animals confined to enclosures was used. In particular, the use of captured deer
      mice (Peromyscus maniculatus) for these studies is compared to the use of
      laboratory-raised deer mice placed in enclosures. This study indicates that the
      higher degree of variability in the responses of wild deer mice make the use of
      enclosure studies advantageous. Positive control studies performed by dosing
      laboratory-raised deer mice with the same PAHs as found on the site were used to
      validate this approach. These studies indicate that immune suppression occurred
      at PAH concentrations an order of magnitude below those required for the
      induction of ethoxyresorufin-O-dealkylase activity.

PMID- 7713035
TI  - The wildlife/human connection: modernizing risk decisions.
AB  - This article proposes that genetic and molecular ecotoxicology can play an
      important role in making policy and risk assessment decisions concerning
      xenobiotics. It calls for a greater awareness by ecotoxicologists to the effects
      in wildlife and humans resulting from transgenerational exposure to synthetic
      chemicals that interfere with gene expression and differentiation. The difficulty
      of recognizing these effects on the endocrine, immune, and nervous systems in
      developing embryos is described and suggests why effects of this nature have
      traditionally not been addressed when determining risk to synthetic chemicals.
      Specific examples are cited of environmental effects on hormonally responsive
      tissue in wildlife populations which could be used as models for assessing human
      exposure to synthetic chemicals. Evidence is presented that the environmental
      load of synthetic chemicals has reached critical levels at which wildlife and
      human health are at risk.

PMID- 7713039
TI  - The genetics of human cancer: implications for ecotoxicology.
AB  - The study of human cancers has provided evidence that malignant progression is
      associated with genetic change. It has been suggested that some genetic
      alterations in tumors may be the result of direct or indirect processes related
      to environmental chemical exposure. This hypothesis has been supported by genetic
      evidence in liver tumors which has associated aflatoxin B1 exposure with the
      detection of inactivating DNA mutations within the human p53 tumor suppressor
      gene. The detection of activating ras oncogene mutations at high frequency in
      liver tumors of feral fish suggest that the survey of mutations in genes, such as
      p53 or other genes, might provide a genetic signature for specific chemical
      exposure in tissues of aquatic animals derived from environmentally damaged
      sites.

PMID- 7713040
TI  - Molecular analysis of bivalve tumors: models for environmental/genetic
      interactions.
AB  - An increase in both the numbers and types of tumors found in finfish and
      shellfish has been noted in the past several decades. In many cases, while the
      increase in tumor incidence can be correlated with increases in aquatic toxicant
      levels, causality cannot be definitively proven. One recent epidemiologic
      investigation identified the prevalence of gonadal cancers as high as 40% in
      softshell clams (Mya arenaria) in Maine and 60% in hardshell clams (Mercenaria
      spp.) from Florida. A second study of these same geographic areas identified
      human mortality rates due to ovarian cancer as significantly greater than the
      national average. The rise in mortality rates in humans correlated with the
      increased use of herbicides in these areas as well as with the appearance of
      significant numbers of gonadal tumors in the clams. Studies were initiated in our
      laboratory to examine the molecular basis of these neoplasms in bivalves. NIH3T3
      transfection assays were used to examine DNA isolated from these molluscan tumors
      for the presence of activated oncogenes. DNAs isolated from advanced tumors in
      both species were able to transform NIH3T3 cells and induce tumors in athymic
      mice. Studies are now underway to identify the gene(s) detected by these assays
      and also to examine the molecular mechanisms of toxic response of herbicide
      exposed clams.

PMID- 7713041
TI  - Assessment of within-group variation in CYP1A mRNA inducibility in
      environmentally exposed and chemically treated Atlantic tomcod.
AB  - CYP1A gene expression has been implicated in the processing of environmental
      procarcinogens and levels of variation in CYP1A mRNA expression are high in both
      environmentally exposed and chemically treated Atlantic tomcod. The objective of
      this study was to evaluate the effects of physical and biological parameters such
      as temperature, sex, and reproductive state on within-group variation in CYP1A
      mRNA induction. Levels of variation in CYP1A mRNA expression were directly
      correlated with mean levels of gene induction. Our results indicate that sex and
      reproductive state, but not temperature, had significant effects on CYP1A mRNA
      inducibility in tomcod; however, these parameters did not account for all
      interindividual variation in CYP1A inducibility. Other intrinsic biological
      factors, such as genetic polymorphisms in molecular pathways leading to CYP1A
      induction, may contribute to the high levels of interindividual variation in
      CYP1A inducibility in Atlantic tomcod.

PMID- 7713042
TI  - Linking genotoxic responses and reproductive success in ecotoxicology.
AB  - The potential of genotoxicity biomarkers as predictors of detrimental
      environmental effects, such as altered reproductive success of wild organisms,
      must be rigorously determined. Recent research to evaluate relationships between
      genotoxic responses and indicators of reproductive success in model animals is
      described from an ecotoxicological perspective. Genotoxicity can be correlated
      with reproductive effects such as gamete loss due to cell death; embryonic
      mortality; and heritable mutations in a range of model animals including
      polychaete worms, nematodes, sea urchins, amphibians, and fish. In preliminary
      studies, the polychaete worm, Neanthes arenaceodentata, and the nematode,
      Caenorhabditis elegans, have also shown the potential for cumulative DNA damage
      in gametes. If DNA repair capacity is limited in gametes, then selected life
      history traits such as long and synchronous periods of gametogenesis may confer
      vulnerability to genotoxic substances in chronic exposures. Recommendations for
      future research include strategic development of animal models that can be used
      to elucidate multiple mechanisms of effect (multiend point) at varying levels of
      biological organization (multilevel).

PMID- 7713045
TI  - Meta-analysis: effect of exercise, with or without dieting, on the body
      composition of overweight subjects.
AB  - OBJECTIVE: To determine if physical training conserves fat-free mass (FFM) in
      overweight men or women during weight loss. DESIGN: Journals published between
      1966 and 1993 were searched by MEDLINE and by handsearch to obtain all reports on
      human subjects in which the effect of exercise on body composition was studied in
      at least two concurrent treatment groups, of which at least one group did, and
      one group did not, undergo an exercise programme designed to promote fat loss.
      The relation between loss of weight, and loss of FFM, was examined by linear
      regression analysis among exercising and non-exercising groups of men or women.
      SUBJECTS: Twenty-eight publications reported results on 226 sedentary men in 13
      groups, 233 exercising men in 14 groups, 199 sedentary women in 23 groups, and
      258 exercising women in 28 groups. RESULTS: Aerobic exercise without dietary
      restriction among men caused a weight loss of 3 kg in 30 weeks compared with
      sedentary controls, and 1.4 kg in 12 weeks among women, but there was little
      effect on FFM. Resistance exercise had little effect on weight loss, but
      increased FFM by about 2 kg in men and 1 kg in women. Regression analysis shows
      that for a weight loss of 10 kg by diet alone the expected loss of FFM is 2.9 kg
      in men and 2.2 kg in women. When similar weight loss is achieved by exercise
      combined with dietary restriction the expected loss of FFM is reduced to 1.7 kg
      in men, and women. It is probable that the FFM conserved by exercise during
      weight loss contains more water and potassium than average FFM. The subjects
      studied were not severely obese. CONCLUSIONS: Aerobic exercise causes a modest
      loss in weight without dieting. Exercise provides some conservation of FFM during
      weight loss by dieting, probably in part by maintaining glycogen and water.

PMID- 7713043
TI  - Metallothionein induction as a measure of response to metal exposure in aquatic
      animals.
AB  - Metallothioneins (MTs) are considered central in the intracellular regulation of
      metals such as copper, zinc, and cadmium. Increased MT synthesis is associated
      with increased capacity for binding these metals and protection against metal
      toxicity. Recent advances in the biochemistry and molecular biology of MTs have
      facilitated research on MTs in aquatic species. For the bivalve mollusc
      Crassostrea virginica, a species frequently used in studies on the toxicology and
      environmental monitoring of metals, the primary structure for MT has been deduced
      from analysis of the proteins and cDNA. Procedures for analysis of MT synthesis
      and MT gene expression have been applied in studies of response to metal
      exposure. Induction of specific MT forms by Cd is concentration- and time
      dependent. The levels of MT-bound metals exhibit a strong relationship with the
      cytosolic metal concentrations in a metal-exposed natural population of oysters.
      Ribonuclease protection assays using sequence-specific antisense RNA probes have
      shown that the MT mRNA structure in this natural population exhibits considerable
      individual variability in the 3'-untranslated region. Although yet to be
      substantiated, the possibility exists that the distribution of this variability
      may be related to the level of environmental metal contamination. One probe
      derived from the coding region is suitable for use in quantitative RPAs for
      oyster MT mRNAs.

PMID- 7713044
TI  - Population genetic structure and ecotoxicology.
AB  - Electrophoretic analyses of population genetic structure, both in the laboratory
      and in the field, have documented significant shifts in allozyme genotype
      frequencies in a variety of aquatic taxa as a result of environmental impacts.
      Studies are documented which indicate that contaminants may select for
      individuals with tolerant allozyme genotypes, causing the potential loss of
      individuals with sensitive genotypes. This may diminish the genetic variability
      and fitness of affected populations and make them more susceptible to extinction
      following a subsequent stress. Future research involving population genetic
      structure and ecotoxicology should focus on determining the mechanism of
      sensitivity, documenting multigenerational effects of chronic laboratory exposure
      on population genetic composition, investigating whether previously stressed and
      genetically impacted populations are more susceptible to further natural and/or
      anthropogenic stressors, and establishing the utility of population genetic
      structure as a sensitive monitor of impacts in aquatic systems and their
      subsequent remediation.

PMID- 7713046
TI  - Effect of varying protein intake on energy balance, protein balance and estimated
      weight gain composition in premature infants.
AB  - OBJECTIVE: We studied the effect of varying only protein intake on energy
      balance, protein balance and estimated weight gain composition in premature
      infants fed either a formula with a protein content of 2.0 g/100 ml (F2) or a
      protein content of 1.5 g/100 ml (F1.5). DESIGN: Premature infants were randomly
      allocated to receive F1.5 or F2. Weight gain composition was estimated from
      protein and energy balances. Energy expenditure was measured with doubly labelled
      water. PATIENTS: F1.5, n = 8; gestational age 32 +/- 3 weeks, birth weight 1716
      +/- 560 g. F2, n = 8; gestational age 32 +/- 3 weeks, birth weight 1544 +/- 488
      g. RESULTS: Infants fed F2 showed a significantly higher protein accretion (P =
      0.003) and weight gain (P = 0.011) when compared to the infants fed F1.5. There
      were no differences in the energy balance. The estimated weight gain composition
      was different between both groups. CONCLUSION: The F2 fed infants had an
      estimated weight gain composition comparable to the reported intrauterine values,
      while the F1.5 fed infants showed a weight gain composition more comparable to
      the reported values of the full term infant. The impact of nutrient composition
      in premature infant formulas on body composition and growth is discussed.

PMID- 7713047
TI  - Validity of food intake measurement of adult Turkish immigrants in The
      Netherlands.
AB  - OBJECTIVE: To study the validity of the reported food intake in a study which was
      designed to assess exposure to dioxins from food sources. DESIGN: Repeated diet
      recalls were used to collect food intake data within a period of four months.
      Data on energy intake were related to computed basal metabolic rate (BMR).
      SETTING AND SUBJECTS: A group of 69 Turkish immigrants (30 men and 39 women aged
      18-59 years) from two municipalities in the Eastern part of the Netherlands,
      whose selected basic socio-demographic characteristics reflect those of adult
      Turkish living in the Netherlands. RESULTS AND CONCLUSIONS: A mean energy intake
      (EI) to BMR ratio of 1.32 for women (mean EI = 8.1 MJ/day) and 1.36 for men (mean
      EI = 10.6 MJ/day) was found. Subjects in the lower and upper tertile of EI/BMR
      ratio differed only in body mass index (BMI: kg/m2). Pearson's correlation
      coefficient between EI/BMR and BMI was -0.39 (P < 0.05). The observed high
      prevalence of obesity in adult Turkish people complicates, as in other cultures,
      an accurate assessment of food intake.

PMID- 7713048
TI  - Dietary survey in a Chinese population.
AB  - OBJECTIVES: To assess food pattern and nutrition profile aiming at planning
      population-based nutrition intervention for chronic diseases control. DESIGN: A
      randomized survey. SETTING: The survey was carried out in Tianjin, one of the
      three largest cities in China. SUBJECTS: 3683 subjects aged 15-64 years old were
      selected by a random stratified multilevel cluster sampling. INTERVENTION: The
      diet was assessed by food weighing plus consecutive individual 3 day food
      records. RESULTS: Distinct differences in dietary pattern and nutrient intakes
      were found between subjects living in urban and rural areas. The diet of urban
      people was richer in fat and high quality protein compared with the diet of rural
      people. Low intakes of vitamin A, calcium, riboflavin, and zinc were found in
      both areas, the situation being worse in the rural areas. The sodium intake and
      sodium:potassium ratio was very high in both areas. Cholesterol intake was much
      higher among the urban people. CONCLUSION: The study suggests that integrated
      nutrition intervention is needed to prevent insufficient intake of some nutrients
      and control dietary risk factors related to chronic diseases.

PMID- 7713049
TI  - Sources of energy from meals versus snacks in 220 people in four age groups.
AB  - OBJECTIVES: To assess meals versus snacks in terms of their contribution to total
      daily energy intake (TDI), macronutrient composition, and food commodity profile.
      DESIGN AND SUBJECTS: Meals and snacks were assessed from 220 7-day weighed
      dietary records. 187 records were obtained from three separate existing studies,
      and reanalysed. These studies contained data on three different age groups in the
      British population; elderly group (n = 88), middle-aged group (n = 40), young
      adult group (n = 59). A separate study of 13-14-year-olds living in Croydon was
      conducted from which 33 usable diet records were collected (adolescent group).
      RESULTS: Boys in the adolescent group consumed more of their TDI as snacks
      (29.0%) compared with men in the young adult (18.9%) and elderly groups (16.6%),
      but not the middle-aged group (25.8%). Females consumed about the same percentage
      of their TDI as snacks; adolescent group 23.6%, young adult group 19.4%, middle
      aged group 21.4%, elderly group 17.9%. Meals were higher in protein and fat, and
      lower in total sugars, compared with snacks. Chocolate confectionery, crisps and
      fizzy drinks and squashes were popular snack foods in the adolescent group.
      Unlike snacks, the food commodity profiles of meals were similar in all age
      groups. CONCLUSIONS: This study shows that foods and drinks consumed as snacks by
      the British public, including the elderly, have a relatively high total sugar
      composition. These results add to the concern relating snack foods with dental
      caries.

PMID- 7713050
TI  - Variation in selenoprotein P concentration in serum from different European
      regions.
AB  - OBJECTIVE: To study the variation in selenoprotein P levels in serum among
      healthy subjects from 17 European regions representing nine countries. SUBJECTS:
      Survey of 414 37-70-year-old subjects (197/217 males/females) from 17 regions.
      RESULTS: The level of selenoprotein P varied significantly among regions and
      countries. When the highest concentration of selenoprotein P encountered in
      samples from Maldegem (Belgium), was set at 100%, the mean concentration for
      other regions was: 92% Barcelona; 91% Ipswich and London; 89% Malmo and
      Vosselaan; 86% Lisbon; 85% Netherlands; 83% Umea; 82% Uppsala; 80% Paris; 79%
      Heidelberg; 78% Gothenburg and Grenoble; 74% Giessen; 71% Ioannina and 69%
      Epirus. When the data were pooled for the nine countries the highest
      selenoprotein P concentration was observed for subjects from Spain. When this
      concentration was set at 100%, the mean concentration for other countries was:
      99% Belgium and United Kingdom, 94% Portugal, 92% Netherlands and Sweden, 86%
      France, 83% Germany and 76% Greece. The linear correlation between serum selenium
      and serum selenoprotein P in the whole sample was 0.68, P < 0.001 (n = 414), and
      it was similar in men and women. Despite this high correlation the mean ratio
      between selenoprotein P and selenium varied 1.3-fold among regions. CONCLUSIONS:
      Both the concentration of selenoprotein P as well as its proportion of total
      serum selenium in adult subjects vary among different European regions. Further
      studies are necessary to evaluate the physiological or medical implications of
      these differences.

PMID- 7713051
TI  - 24 h energy expenditure during a standardized activity protocol in young and
      elderly men.
AB  - OBJECTIVE: The effect of age on energy expenditure was studied. DESIGN: Case
      control study. SETTING: Respiration chamber at the University of Maastricht.
      SUBJECTS: Thirteen young men (27 +/- 4 years) and ten elderly men (74 +/- 5
      years), were recruited with advertisements in local media. METHODS: In a 36 h
      experiment, 24 h energy expenditure (EE), sleeping metabolic rate (SMR), diet
      induced thermogenesis (DIT) and energy expenditure of physical activity (EEact)
      were measured while subjects performed an activity protocol in a respiration
      chamber under strictly controlled conditions. RESULTS: SMR as a function of fat
      free mass (FFM) was not different between both age groups. 24 h EE during a
      standardized activity protocol was significantly higher for the young men (young
      men: 12.85 +/- 1.53 MJ/d; elderly men: 10.90 +/- 1.12 MJ/d; P = 0.011). The DIT
      expressed as MJ/d was significantly higher for the young subjects but similar
      when expressed as percentage of energy intake (young men: 13.10 +/- 5.44%;
      elderly men: 9.88 +/- 3.86%). The resulting figure for EEact (24 h EE--SME--DIT)
      was the same for young and elderly men (young men: 3.11 +/- 0.71 MJ/d; elderly
      men: 3.05 +/- 0.64 MJ/d). CONCLUSION: The results indicate that mean energy costs
      for low intensity daily activities (some daily household activities and a bench
      stepping exercise) were the same for young and elderly men.

PMID- 7713052
TI  - Evaluation of near infra-red interactance for assessment of subcutaneous and
      total body fat.
AB  - OBJECTIVE: Near infra-red interactance (NIRI) has been used for assessment of
      total body fatness, but its relationship with composition at the measurement site
      is not clear. This study examines the relationship of interactance with
      subcutaneous adipose tissue and muscle thickness as well as total body fat
      content. DESIGN: (i) Validation of NIRI by comparison with subcutaneous tissue
      thicknesses from ultrasound. (ii) Cross-validation of techniques for estimation
      of body fat content. SETTING: Laboratory. SUBJECTS: (i) 54 young adults (27 male
      and 27 female) and (ii) 63 middle-aged men. INTERVENTIONS: Measurements of
      subcutaneous adipose tissue thickness and muscle thickness using ultrasound, near
      infra-red interactance (Futrex 5000) and skinfold thicknesses were made at five
      sites in young adults. In middle-aged men total body fat was assessed by
      densitometry, NIRI and skinfold thickness. Measurements were made in duplicate by
      a single trained observer. RESULTS: Interactance measurements were related to
      subcutaneous adipose tissue thickness, although the relationship varied according
      to measurement site r = 0.09 at anterior thigh to 0.78 at biceps; P = 0.31 to <
      0.0001). Muscle thickness explained additional variance in interactance only at
      biceps in women. Subcutaneous adipose tissue thickness correlated better with
      skinfold thickness (r = 0.56 to 0.92; P = 0.002 to < 0.0001) than with
      interactance. Mean difference in fat mass from densitometry +/- 95% limits of
      agreement was -1.61 +/- 7.68 kg for NIRI and -2.84 +/- 6.56 kg for skinfold
      thickness in middle-aged men. NIRI tended to underestimate higher (and
      overestimate lower) levels of fatness. CONCLUSIONS: NIRI performed no better than
      skinfolds in assessment of either subcutaneous or total body fat.

PMID- 7713053
TI  - The growth of Malawian preschool children from different socioeconomic groups.
AB  - OBJECTIVE: The growth of Malawian preschool children from different socioeconomic
      groups was examined to determine the relevance of the NCHS/WHO growth reference
      data for assessing child nutritional status in Malawi. DESIGN: The study involved
      a comparison of anthropometric data from three cross-sectional surveys of
      preschool children over 24 months of age. SETTING: Malawi, Central Africa.
      SUBJECTS: Anthropometric measurements were taken on high income Malawian children
      (n = 380) during a census of affluent preschools in the country's three major
      urban centres. Comparative data were obtained from two existing sample surveys of
      low income urban children (n = 225) and rural village children (n = 667).
      RESULTS: The distribution of weight-for-age Z-scores (HAZ) for the high income
      children 24-35 months of age closely resembled the NCHS/WHO child reference
      population (mean HAZ = -0.21; SD = 1.05). After this age HAZ decreased to a mean
      value of -0.58 between 60 and 71 months. Large differences in growth were
      observed between children from different socioeconomic groups. Regression
      analysis showed that at 24 months the high income children were, on average, 6.6
      cm taller than the low income urban children (P < 0.001), and 9.2 cm taller than
      the rural children (P < 0.001). By 59 months of age these differences increased
      to 9.6 cm and 11.1 cm, respectively. CONCLUSIONS: Although some questions remain
      regarding the growth potential of Malawian children, the results suggest the
      NCHS/WHO reference data are relevant for Malawi and the high levels of child
      stunting found in the country are due to environmental not genetic factors.

PMID- 7713054
TI  - No evidence of fontanelle-bulging episodes after vitamin A supplementation of 6-
      and 9-month-old infants in Guinea Bissau.

PMID- 7713055
TI  - Experimental and clinical studies on the putative therapeutic efficacy of
      cerebral irradiation (radiotherapy) in epilepsy.
AB  - 1. The majority of the published literature on the radiotherapeutic treatment of
      epilepsy suffers because it has involved neither radiotherapists nor
      epileptologists. 2. Papers have either been written describing an incidental
      beneficial effect (these suffer from being retrospective analyses) or by
      enthusiasts (where one must question patient selection). In addition there are a
      small number of very detailed and useful individual case reports. 3. Despite the
      reservations it would appear that radiation can have beneficial effects on
      seizures, and this effect has been described for a wide variety of conditions
      using a wide variety of treatment modalities. 4. There are grounds for
      prospective clinical trials to test the putative therapeutic efficacy of cerebral
      irradiation. However, it is essential that these are carried out by a group
      involving an established epilepsy surgery programme and a radiotherapy department
      conversant with the complex issues involved in focussed radiation treatment.

PMID- 7713056
TI  - Morphological changes in the hippocampus in amygdaloid kindled mouse.
AB  - To clarify the origin and maintenance of epileptogenesis, morphological changes
      in the hippocampus of amygdaloid-kindled mice were analyzed at different stages
      of kindling. The granule cell size in dentate gyrus and the pyramidal cell size
      in CA1 were clearly decreased depending on seizure stage. The cell size in CA2
      was increased and density in dentate gyrus and CA2 was reduced, significantly.
      The morphological changes in hippocampus associated with kindling must be closely
      related to the acquisition and the maintenance of epileptogenesis. The results
      support the hypothesis that seizure-induced damage of neurons may lead to
      formation of new synaptic connections that produce abnormal hyperexitability and
      result in seizures.

PMID- 7713057
TI  - Respiratory drive during status epilepticus and its treatment: comparison of
      diazepam and lorazepam.
AB  - In order to examine the respiratory effects of tonic-clonic seizures and their
      treatment with i.v. diazepam or lorazepam, we utilized a spontaneously breathing
      piglet seizure model. A tracheostomy, arterial catheter, and epidural electrodes
      were inserted and pigs were maintained under ketamine anesthesia. After baseline
      recordings, seizures were induced with a pentylenetetrazol (PTZ) bolus and a 20
      min infusion (5-6 mg/kg/min). After 10 min of PTZ infusion, randomly assigned
      animals received diazepam (D; N = 7; 0.5 mg/kg), lorazepam (L; N = 7; 0.2 mg/kg),
      or 0.9% saline (C; N = 7; controls) by rapid peripheral vein injection. Minute
      ventilation (Ve), Pa(CO2), and the pressure change in response to airway
      occlusion at end-expiration (P0.1) were measured at standard intervals. All
      groups had comparable increases in respiratory drive during untreated seizures.
      Changes in Ve and P0.1 were reduced to at or below baseline values in groups D
      and L, but not C, from 2 to 45 min after treatment (P < 0.05). No significant
      changes were observed in Pa(CO2) after either intervention. Following
      anticonvulsants, the cumulative duration of seizures was significantly reduced in
      L and D groups, compared to C (P < 0.05). We conclude that increases in
      respiratory drive occur during tonic-clonic seizures induced with PTZ.
      Amelioration of seizure activity with lorazepam or diazepam results in a
      reduction in respiratory drive, but not respiratory failure, in this
      tracheostomized model.

PMID- 7713058
TI  - The substantia nigra pars reticulata, seizures and Fos expression.
AB  - The induction of the proto-oncogene c-fos has been used extensively to identify
      spatially distributed neural systems activated by seizures. The substantia nigra
      pars reticulata (SNpr) has been implicated as a critical structure in neural
      networks involved in the modulation of seizure expression, yet the SNpr has not
      been reported to express Fos following seizures induced in a variety of seizure
      paradigms. In this study we determined whether (1) the temporal characteristics
      of Fos induction in the SNpr were different than those of other brain areas
      following kindled seizures, (2) neurons in the SNpr possess the cellular
      machinery to express Fos, (3) Fos can be induced in SNpr by direct electrical
      stimulation, and (4) Fos expression is induced in the SNpr following kainate or
      pilocarpine-induced status epilepticus. Results indicate that Fos is not induced
      in SNpr at any time point (1-12 h) after kindled seizures, and that serum
      response factor, a constitutively expressed nuclear protein necessary for Fos
      expression, is present in SNpr neurons. Results further indicate that Fos
      expression in the SNpr is induced following either direct electrical stimulation
      or pilocarpine status, but not status elicited by kainate. We conclude that, in
      so far as the SNpr represents a critical structure for modulating seizure
      expression, seizure activity does not represent a sufficient stimulus to induce
      Fos in SNpr neurons. Further, the neural networks defined by Fos expression
      following seizure may be incomplete, and should be interpreted conservatively.

PMID- 7713059
TI  - Felbamate modulates the strychnine-insensitive glycine receptor.
AB  - Felbamate (2-phenyl-1,3-propanediol dicarbamate) is a novel anticonvulsant
      substance whose mechanism of action is not clearly understood. The present
      investigation examined its ability to modulate the strychnine-insensitive glycine
      receptor associated with the N-methyl-D-aspartate (NMDA) receptor. Felbamate
      decreased the magnitude of glycine (100 microM)-enhanced NMDA (100 microM)
      induced intracellular calcium ([Ca2+]i) transients in mouse cerebellar granule
      cells which had been loaded with the Ca(2+)-sensitive fluorescent probe indo-1
      acetoxymethyl ester (indo-1/AM). This effect of felbamate was concentration
      dependent, with a maximal effect observed at 300 microM (65 +/- 4% of control).
      In the Frings audiogenic seizure-susceptible mouse model of reflex epilepsy, the
      glycine agonist D-serine (150 nmol, i.c.v.) completely blocked the anticonvulsant
      activity of a maximally effective dose of felbamate (19 mg/kg, i.p.). This effect
      of D-serine could be reversed by increasing the administered dose of felbamate to
      29 mg/kg. Furthermore, administration of D-serine (300 nmol, i.c.v.) to felbamate
      treated Frings mice produced a parallel right shift in felbamate's anticonvulsant
      dose-response curve (ED50s: 9.4 mg/kg for felbamate vs. 17.7 mg/kg for felbamate
      + D-serine). The results obtained in this investigation suggest that the ability
      of felbamate to modulate the strychnine-insensitive glycine receptor may be
      physiologically and behaviorally relevant to its anticonvulsant mechanism of
      action.

PMID- 7713060
TI  - Psychomotor seizures of temporal lobe onset: analysis of symptom clusters and
      sequences.
AB  - We analyzed 91 psychomotor seizures from 31 patients seizure free at least one
      year after temporal lobectomy (implying temporal lobe onset). Fifty symptoms were
      looked for in every seizure and their time of onset and ending noted. Statistical
      analysis was used to define symptom clusters and the order of appearance of
      symptoms. Of the eighteen most common symptoms examined, all of these symptoms
      form a tight cluster showing a high degree of correlation. Within this cluster,
      there was a tendency towards the following subclusters: (a) epigastric aura,
      ictal vomiting, alimentary and hand automatisms; (b) behavioral arrest, complete
      loss of consciousness, staring and bilateral facial contraction; (c) unilateral
      dystonic posturing of an arm, mimetic automatisms, complex gestures, ictal speech
      and partial loss of consciousness; (d) looking around, agitation, vocalizations
      and whole body movements. We also found a strong correlation between epigastric
      sensation and ictal vomiting in psychomotor seizures arising from the right but
      not the left temporal lobe. The commonest sequence of symptoms was: behavioral
      arrest followed by alimentary and hand automatisms, looking around and whole body
      movements, in that order.

PMID- 7713061
TI  - Gender differences in post-temporal lobectomy verbal memory and relationships
      between MRI hippocampal volumes and preoperative verbal memory.
AB  - Thirty-three men and 42 women who underwent left, and 26 men and 24 women who
      underwent right temporal lobectomy (TL) were studied retrospectively to determine
      if there were sex differences in (1) verbal memory outcome, and (2) relationships
      between verbal memory and magnetic resonance imaging (MRI) hippocampal volumes.
      All patients were left hemisphere language dominant. The surgical specimen and
      MRI were consistent only with mesial temporal sclerosis (MTS). Verbal memory was
      evaluated by Logical Memory percent retention (LMPER) from the Wechsler Memory
      Scale-Revised (WMS-R). Women experienced a significant improvement while men
      experienced a significant decline in postoperative LMPER. The difference between
      right and left hippocampal volumes predicted verbal memory outcome in both men
      and women. Preoperative LMPER was positively correlated with both the left and
      right hippocampal volumes in left TL women only. No verbal memory sex differences
      or correlations between LMPER and MRI data were found in the right TL group. The
      data support the presence of human neurocognitive sexual dimorphism. Verbal
      memory abilities supported by the hippocampus are less lateralized in women with
      left temporal lobe epilepsy and mesial temporal sclerosis. Women appear to have
      greater verbal memory plasticity following early left mesial temporal lobe
      insult.

PMID- 7713062
TI  - FDG-PET in children and adolescents with partial seizures: role in epilepsy
      surgery evaluation.
AB  - We used FDG-PET to measure interictal glucose metabolism in 16 children and
      adolescents (mean age 14.7 years) and complex partial seizures (CPS) (mean
      seizure onset age 5.0 years). Video-EEG localized the epileptic foci. Glucose
      metabolism was determined in 14 paired anatomic areas using a standard template.
      PET hypometabolism was defined as greater than 15% asymmetry. Nine of the 13
      (69%) patients with a unilateral EEG focus had regional hypometabolism
      ipsilateral to the epileptogenic zone. Three subjects had bilateral EEG foci; all
      had nonfocal PET. MRI (15 patients) concurred with EEG and PET in two, and was
      normal in seven of nine with focal hypometabolism. One of seven patients with
      normal PET had a focal MRI abnormality. FDG-PET results are similar to those
      found in adults, but are present earlier in the natural history of CPS (9.7 vs
      22.2 years duration epilepsy) than previously reported. The presence of FDG-PET
      hypometabolism may be associated with a poor response to drug treatment. PET can
      identify metabolic abnormalities associated with epileptic foci in children and
      adolescents and is useful in directing surgical intervention for the control of
      refractory complex partial epilepsy.

PMID- 7713064
TI  - Exercise-induced splitting of the inorganic phosphate peak: investigation by time
      resolved 31P-nuclear magnetic resonance spectroscopy.
AB  - To investigate the splitting of the inorganic phosphate (Pi) peak during exercise
      and recovery, a time-resolved 31phosphorus nuclear magnetic resonance
      spectroscopy (31P-MRS) technique was used. Seven healthy young sedentary male
      subjects performed knee flexion exercise in the prone position inside a 2.1-T
      magnet, with the surface coil for 31P-MRS being placed on the biceps femoris
      muscle. After a 1-min warm-up without loading, the exercise intensity was
      increased by 0.41 W at 15-s intervals until exhaustion, followed by a 5-min
      recovery period. The 31P-MRS were recorded every 5 s during the rest-exercise
      recovery sequence. Computer-aided contour analysis and pixel imaging of the Pi
      and phosphocreatine peaks were performed. Five of the seven subjects showed two
      distinct Pi peaks during exercise, suggesting two different pH distributions in
      exercising muscle (high pH and low pH region). In these five subjects, the high
      pH increased rapidly just after the onset of exercise, while the low-pH peak
      increased gradually approximately 60 s after the onset of exercise. During
      recovery, the disappearance of the high-pH peak was more rapid than that of the
      low-pH peak. These findings suggest that our method 31P-MRS provides a simple
      approach for studying the kinetics of the Pi peak and intramuscular pH during
      exercise and recovery.

PMID- 7713063
TI  - Felbamate in the treatment of acquired epileptic aphasia.
AB  - A previously healthy six year old boy developed severe receptive and expressive
      aphasia, multifocal epileptiform discharges, and refractory clinical seizures
      consistent with acquired epileptic aphasia. The patient experienced complete
      seizure control and almost complete return of language skills following the
      addition of felbamate. This is the first case of successful treatment of acquired
      epileptic aphasia using felbamate.

PMID- 7713065
TI  - Limitations on arteriovenous cooling of the blood supply to the human brain.
AB  - Arteriovenous heat transfer (AVHT) is a thermoregulatory phenomenon which
      enhances tolerance to thermal stress in a variety of animals. Several authors
      have speculated that human responses to thermal stress reflect AVHT in the head
      and neck, even though primates lack the specialized vascular arrangements which
      characterize AVHT in other animals. We modeled heat transfer based on the
      anatomical relationships and blood flows for the carotid artery and associated
      venous channels in the human neck and cavernous sinus. Heat transfer rate was
      predicted using the "effectiveness-number of transfer units" method for heat
      exchanger analysis. Modeling showed that AVHT is critically dependent upon (1)
      heat exchanger effectiveness and (2) arteriovenous inlet temperature difference.
      Predicted heat exchanger effectiveness is less than 5.5% for the neck and 0.3%
      for the cavernous sinus. These very low values reflect both the small
      arteriovenous interface for heat exchange and the high flow rate in the carotid
      artery. In addition, humans lack the strong venous temperature depression
      required to drive heat exchange; both the cavernous sinus and the internal
      jugular vein carry a large proportion of venous blood warmed by its passage
      through the brain as well as a small contribution from the face and scalp, whose
      temperature varies with environmental conditions. Under the most optimistic set
      of assumptions, carotid artery temperature would be lowered by less than 0.1
      degrees C during its passage from the aorta to the base of the brain.
      Physiologically significant cooling of the blood supply to the brain cannot occur
      in the absence of a suitably scaled site specialized for heat exchange.

PMID- 7713066
TI  - Sympathetic nervous activity and cardiovascular variability after a 3-day tail
      suspension in rats.
AB  - The effects of a 3-day tail suspension on central and peripheral sympathetic
      activity were studied in rats by determining the in vivo noradrenaline (NA)
      turnover in the brain cell groups involved in central blood pressure control (A1,
      A2, A5 and A6) and in two peripheral organs, heart and kidneys. In addition,
      cardiovascular parameters and their variabilities were investigated by recording
      blood pressure (BP) and heart rate (HR) before and after suspension. These
      measurements were processed by spectrum analysis to assess the influence of tail
      suspension on autonomic balance. The NA turnover in the suspended rats was
      markedly reduced in A2 (-49%, P < 0.01) and A5 (-38%, P < 0.01) nuclei but
      unchanged in A1 and A6 cell groups compared with the control rats. Peripheral NA
      turnover was decreased in cardiac atria (-44%, P < 0.001) and ventricles (-27%, P
      < 0.01) while it was unchanged in kidneys after suspension. The BP, HR and their
      variabilities were similar in both groups of animals and showed no changes after
      suspension compared with baseline values. Spectrum analysis of BP and HR in our
      conscious suspended rats revealed no changes in power spectrum density or in peak
      frequencies. The discrepancy between the decrease in central sympathetic activity
      and the absence of changes in cardiovascular parameters after tail suspension
      raises the question of the validity of the tail suspended rat model when studying
      the cardiovascular deconditioning observed in humans after an exposure to actual
      or simulated weightlessness.

PMID- 7713068
TI  - Effect of eccentric exercise on plasma enzyme activities previously elevated by
      eccentric exercise.
AB  - The purpose of this study was to investigate whether plasma activities of
      creatine kinase (CK) and glutamic-oxaloacetic transaminase (GOT), elevated by
      eccentric exercise, would be affected by a second bout of eccentric exercise. A
      group of 26 male students [20.3 (SD 1.9) years] were placed in one of three
      groups. Group A (n = 8) performed one bout of 24 maximal eccentric actions (ECC)
      of the forearm flexors (ECC1), and groups B (n = 10) and C (n = 8) performed two
      bouts of ECC (ECC1, ECC2). The ECC2 was performed by the opposite arm 3 days
      (group B) or 5 days (group C) after ECC1. None of the subjects had performed this
      eccentric exercise prior to this study. Maximal isometric force (MIF), range of
      motion (ROM), upperarm circumference (CIR), muscle soreness level (SOR), and
      plasma CK and GOT activities were measured before and for 8 days (group B) or 10
      days (groups A, C) postexercise. The MIF, ROM, CIR, and SOR changed significantly
      after exercise (P < 0.01), and no significant differences in changes were found
      between ECC1 and ECC2, or among the groups. This suggested that ECC1 and ECC2
      produced a similar stress to the forearm flexor muscles. Therefore, it was
      expected that CK and GOT activities would show similar increases after ECC1 and
      ECC2. However, increases in CK and GOT activities after ECC2 were significantly
      smaller (P < 0.01) than after ECC1 in both groups B and C. The results of this
      study confirmed that CK and GOT responses were diminished when initial blood
      enzyme activities were elevated.

PMID- 7713067
TI  - In vivo human myocardial metabolism during aerobic exercise by phosphorus-31
      nuclear magnetic resonance spectroscopy.
AB  - A few studies have been made in vivo on human myocardial energy metabolism.
      Hence, no discussion has taken place on metabolism during exercise or of training
      effects on metabolism. We examined human myocardial energy metabolism at rest and
      during exercise, and also training effects on the metabolism by phosphorus-31
      nuclear magnetic resonance (31P NMR)-spectroscopy. Six sedentary male students
      (Cont) and six male long distance runners (Tr) were the subjects. Energy
      metabolism data were obtained from myocardium during rest and exercise by the
      region selection method using 31P NMR. Rotation of the legs while riding a
      bicycle, which was fitted with an ergometer we had made ourselves for NMR,
      imposed given exercise intensities. The heart rate was measured in a stationary
      phase during exercise. Although the heart rate at rest in the Tr group was
      significantly lower [Tr, 52.5 (SD 3.1) beat.min-1; Cont, 67.1 (SD 2.9) beat.min
      1], no significant difference was observed in myocardial energy metabolism using
      the 31P NMR method [Tr, phosphocreatine/beta-adenosine 5'-triphosphate (PCr/beta
      ATP); 1.51 (SD 0.02); Cont, 1.51 (SD 0.01)]. When NMR measurements were
      investigated at two different intensities of exercise, heart rates in the Cont
      group were significantly higher by about 20 beat.min-1 than those in the Tr group
      at both exercise intensities, while no difference in energy metabolism was
      observed between the groups or between rest and exercise [Tr, 75.9 (SD 3.6), 88.3
      (SD 3.7) beat.min-1; PCr/beta-ATP 1.51 (SD 0.03), 1.51 (SD 0.03); Cont, 95.9 (SD
      2.4), 115.1 (SD 3.5) beat.min-1, PCr/beta-ATP 1.51 (SD 0.01), 1.51 (SD
      0.04)].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713069
TI  - The effects of two types of clothing on seasonal cold tolerance.
AB  - This study investigated the effects of two types of clothing, leaving legs
      covered or uncovered, on seasonal cold tolerance in women. Experiments were
      carried out to compare cold tolerance at an ambient temperature (Ta) of 10
      degrees C in December between two groups of subjects, who wore either knee-length
      skirts (skirt group) or full-length trousers (trouser group) for 3 months from
      September to November. The main results are summarized as follows: rectal
      temperatures continued to fall for 40 min in the trouser group when the subjects
      were covered by a blanket, while it became stable in 30 min in the skirt group;
      rectal temperatures showed greater increases in the skirt group when the blanket
      was removed after 40 min exposure to Ta of 10 degrees C; metabolic heat
      production was kept significantly lower in the skirt group when uncovered or
      covered by a blanket at Ta of 10 degrees C; metabolic heat production was
      negatively correlated with mean skin temperature and was always higher in the
      trouser group when measured at the same mean skin temperature; in the uncovered
      condition diastolic blood pressure increased significantly in the trouser group
      but not in the skirt group. These results would suggest that the subjects who
      wore skirts for 3 months from September to November had improved their ability to
      tolerate the cold.

PMID- 7713070
TI  - Autonomic nervous control of heart rate at altitude (5050 m).
AB  - To investigate possible changes in autonomic regulation of heart rate as a result
      of acclimatization to high altitude, indexes of autonomic nervous activity were
      obtained non invasively by spectrum analysis of heart rate variability on five
      healthy male subjects [age, 31 (SEM 2) years] during a postural change from
      supine to seated, both at sea level and after 1 month of exposure to an altitude
      of 5050 m. Heart rate fluctuations at the respiratory frequency (high frequency,
      HF) are mediated by the parasympathetic system whereas fluctuations at about 0.1
      Hz (low frequency, LF) are due to both sympathetic and parasympathetic nervous
      systems. Maximal heart rate, as measured during an incremental exercise test,
      decreased from 184 (SEM 5) beats.min-1 at sea level to 152 (SEM 2) beats.min-1 at
      5050 m. At sea level, the change in posture from supine to seated induced an
      increase in LF amplitude accompanied by an increase or a decrease in HF
      amplitude, whereas after 1 month at altitude the HF amplitude decreased in all
      subjects, with little or no change in LF amplitude. These results indicate a
      changed strategy of heart rate regulation after acclimatization to high altitude.
      At sea level, the postural change induced an increase in sympathetic activity in
      all subjects with different individual vagal responses, whereas at altitude the
      postural change induced a net decrease in vagal tone in all subjects, with little
      or no change in sympathetic activity. These results corroborate the reported
      reduced sensitivity of the heart to adrenergic drive in chronic hypoxia, which
      may, at least in part, explain the decreased maximal heart rate in altitude
      acclimatized human subjects.

PMID- 7713071
TI  - Electromyographic correlates of the transition from aerobic to anaerobic
      metabolism in treadmill running.
AB  - This study analysed the changes in electromyographic (EMG) activity of the vastus
      lateralis, biceps femoris and gastrocnemius muscles during incremental treadmill
      running. The changes in EMG were related to the lactate and ventilatory
      thresholds. Ten trained subjects participated in the study. Minute ventilation,
      oxygen consumption, carbon dioxide expired and the fraction of oxygen in the
      expired gas were recorded continuously. Venous blood samples were collected at
      each exercise intensity and analysed for lactate concentration. The EMG were
      recorded at the end of each exercise intensity using surface electrodes. The EMG
      were quantified through integration (iEMG) and by calculating the mean power
      frequency (MPF). The iEMG measurements were characterized by a breakpoint in the
      vastus lateralis and/or gastrocnemius muscles in eight of the subjects tested.
      However, the results indicated that blood lactate concentrations had already
      begun to increase in a nonlinear fashion before the iEMG breakpoint had been
      surpassed. Consequently, the occurence of the lactate threshold cannot be
      attributed solely to the change in motor unit recruitment or rate coding patterns
      demonstrated by the iEMG breakpoint. The ventilatory threshold was shown to be a
      far more reliable and convenient noninvasive predictor of the lactate threshold
      in comparison with EMG techniques. In conclusion, the EMG measurements used in
      this study (i.e. iEMG and MPF) were not considered to be viable noninvasive
      determinants of the aerobic-anaerobic transition phase in treadmill running.

PMID- 7713072
TI  - Physiological consequences of acculturation: a 20-year study of fitness in an
      Inuit community.
AB  - Surveys in 1969/1970, 1979/1980, and 1989/1990 assessed physical fitness among
      adult Inuit living in Igloolik, Northwest Territories, Canada, during a period of
      rapid acculturation to a sedentary lifestyle. MANOVA for age, cohort, and age
      cohort effects indicated significant trends to greater skinfold readings [male
      (M) and female (F)] and body mass (F only), a lower handgrip and knee extension
      force (M and F), and lower step test predictions of aerobic power (M and F) in
      the more recent cohorts, with no change of forced vital capacity, 1-s forced
      expiratory volume, or hemoglobin level. By 1989/1990, continuing hunters tended
      to have thicker skinfolds than other villagers, and showed no advantage of
      aerobic power. The average fitness of the sample when tested in 1989/1990 was
      comparable with that of sedentary populations in Southern Canada, but a minority
      of villagers who now practiced regular sport had conserved the high levels of
      fitness that were observed in 1969/1970. We conclude that the fitness of this
      community appears to have deteriorated markedly as it has become more sedentary,
      and we thus recommend that health authorities develop methods of promoting an
      active lifestyle that are culturally appropriate to the populations of
      circumpolar settlements.

PMID- 7713073
TI  - Energy expenditure and cardiorespiratory responses at the transition between
      walking and running.
AB  - We investigated whether the spontaneous transition between walking and running
      during moving with increasing speed corresponds to the speed at which walking
      becomes less economical than running. Seven active male subjects [mean age, 23.7
      (SEM 0.7) years, mean maximal oxygen uptake (VO2max), 57.5 (SEM 3.3) ml.kg-1.min
      1, mean ventilatory threshold (VTh), 37.5 (SEM3) ml.kg-1.min-1] participated in
      this study. Each subject performed four exercise tests separated by 1-week
      intervals: test 1, VO2max and VTh were determined; test 2, the speed at which the
      transition between walking and running spontaneously occurs (ST) during
      increasing speed (increases of 0.5 km.h-1 every 4 min from 5 km.h-1) was
      determined; test 3, the subjects were constrained to walk for 4 min at ST, at ST
      +/- 0.5 km.h-1 and at ST +/- 1 km.h-1; and test 4, the subjects were constrained
      to run for 4 min at ST, at ST +/- 0.5 km.h-1 and at ST +/- 1 km.h-1. During
      exercise oxygen uptake (VO2), heart rate (HR), ventilation (VE), ventilatory
      equivalents for oxygen and carbon dioxide (VE/VO2, VE/VCO2), respiratory exchange
      ratio (R), stride length (SL), and stride frequency (SF) were measured.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7713074
TI  - Prediction of physical activity level in adulthood by physical characteristics,
      physical performance and physical activity in adolescence: an 11-year follow-up
      study.
AB  - The purpose of the study was to investigate to what extent the physical activity
      pattern in adulthood can be predicted by physical characteristics, performance
      and activity in adolescence. A group of 62 men and 43 women completed a
      questionnaire concerning physical activity during their leisure time at the ages
      of 16 and 27 years. An activity index produced from the questionnaire. At the age
      of 16 years, the subjects were also tested for strength (strength test battery)
      and running performance (9-min run). Maximal oxygen uptake (VO2max) was estimated
      from a submaximal test and a muscle biopsy specimen was taken and analysed for
      fibre types (percentages of types I, IIA, IIB). The proportion of subjects
      engaged in some kind of physical activity during their leisure time was
      approximately 70% among the women and 80% among the men at both ages. The time
      spent on physical activity (minutes per week) decreased with age for the men but
      not for the women. The women devoted less time to physical activity than the men
      both at age 16 and 27 years. The attitude to endurance activities had changed to
      a more positive attitude among the women and to a less positive attitude among
      the men at age 27 years. The aerobic potential (VO2max and percentage of type I
      fibre), running performance, strength performance, physical activity and marks in
      physical education at age 16 years explained 82% of the physical activity level
      in adulthood for the women and 47% for the men.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713075
TI  - Theoretical and experimental behaviour of the muscle viscosity coefficient during
      maximal concentric actions.
AB  - The aim of this study was to calculate the theoretical variation of the nonlinear
      damping factor (B) as a function of the muscle shortening velocity, and then to
      compare the theoretical values with the experimental data obtained on both the
      elbow flexor and the ankle extensor muscles. The theoretical variation of the B
      factor was determined from a muscle model consisting of a contractile component
      in parallel with a viscous damper both in series with an elastic component, and
      by using, the characteristic equation of the force velocity curve. In this muscle
      model, the viscous element modelled the inability of the muscle to generate as
      big a contracting force (while shortening) as possible under isometric
      conditions. Eight volunteer subjects performed maximal concentric elbow flexions
      and ankle extensions on an isokinetic ergometer at angular velocities of 60, 120,
      180, 240, 300 and 360 degrees.s-1, and held two maximal isometric actions at an
      elbow angle of 90 degrees (0 degrees corresponds to the full extension) and at an
      ankle angle of 0 degree (0 degree corresponds to the foot flexion of 90 degrees
      relative to the leg axis). From these measurements, the force and the shortening
      velocity values of each muscle were determined by using a musculo-skeletal model
      of the joint. The results showed that the theoretical behaviour of the B factor
      would seem to be dependent on the shortening velocity and on the parameter which
      varies according to the muscle fibre type composition and affects the curvature
      of the force-velocity curve (af).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713076
TI  - The relationship between directly measured human cerebral and tympanic
      temperatures during changes in brain temperatures.
AB  - The present study was performed to investigate the relationship between
      noninvasive measurements of core temperature and intracranial temperature
      measurements in humans. At 2-3 weeks following minor subarachoid haemorrhage,
      five patients were studied during open brain surgery. All patients were fully
      conscious and free of neurological symptoms at the time of surgery. During
      craniotomies in the frontotemporal region, temperatures between the dura and
      brain surface were on average 0.58 (SD 0.51) degrees C lower than those near the
      mesencephalon. During the 60-90 min following the initial exposure of the brain
      surface to the ambient temperature of 24 degrees C, subdural temperature at the
      convexity decreased by 0.72 (SD 0.43) degrees C and subdural temperature at the
      basis decreased by 0.36 (SD 0.17) degrees C. During the same period,
      mesencephalon temperature decreased by 0.22 (SD 0.10) degrees C. The decreases of
      cerebral temperatures were followed by a similar decrease in tympanic temperature
      of 0.28 (SD 0.10) degrees C but by an increase in rectal temperature of 0.22 (SD
      0.13) degrees C and an increase in oesophageal temperature of 0.20 (SD 0.20)
      degrees C. The maximal shift of frontal skin temperature during the same period
      amounted to +0.04 (SD 0.21) degrees C. The findings would seem to support the
      thesis that a direct relationship does exist between tympanic and brain
      temperatures in humans and that of the externally accessible body temperatures,
      tympanic temperatures giving the best approximation of average cerebral
      temperature.

PMID- 7713078
TI  - Noninvasive assessment of in vivo glycogen kinetics in humans: effect of
      increased physical activity on glycogen breakdown and synthesis.
AB  - In vivo glycogen kinetics was estimated with the simultaneous use of indirect
      calorimetry and tracer technology in healthy humans during 24-h periods with low
      or moderate physical activity (1 or 3 exercise sessions each day). Two 13C
      carbohydrates meals were administered at 9.30 a.m. and 1.30 p.m., and one 12C
      carbohydrates meal at 6.30 p.m. Net carbohydrate oxidation (net CHO ox) was
      measured over a 24 h period by indirect calorimetry and oxidation of 13C-labelled
      carbohydrates (13C CHO ox) was estimated from 13CO2 production. Glycogen
      breakdown, assessed for the period 8.15 a.m.-6.30 p.m. as the difference between
      net CHO ox and 13C CHO ox, was increased 1.6 times with three exercise sessions
      [123.3 (SEM 8.0) g] versus one session [77.9 (SEM 7.7) g, P < 0.0001].
      Carbohydrate balances over 24 h were close to zero under both conditions,
      indicating that glycogen breakdown was matched by an equivalent glycogen
      synthesis. It was concluded that simultaneous use of indirect calorimetry and
      tracer technology may make possible the estimation of glycogen kinetics in
      humans. Moderate physical activity enhanced both glycogen breakdown and
      synthesis. This stimulation of glycogen metabolism may therefore play a role in
      the enhanced insulin sensitivity induced by physical exercise.

PMID- 7713077
TI  - Y-intercept of the maximal work-duration relationship and anaerobic capacity in
      cyclists.
AB  - The degree to which the y-intercept (Y-int) of the linear regression of maximal
      work output on exercise duration represented anaerobic capacity was determined in
      ten well-trained male cyclists [peak oxygen uptake (VO2peak) = 69.8 (SD 4.2)
      ml.kg-1.min-1]. Each cyclist performed three exhausting cycle sessions on
      separate occasions; the mean exercise durations were 312, 243 and 141 s for the
      low (approximately 104% VO2peak), medium (approximately 108% VO2peak) and high
      (approximately 113% VO2peak) intensities respectively, and Y-int (kilojoules;
      joules per kilogram) was derived from the regression of work output on exercise
      duration. The muscle anaerobic adenosine 5'-triphosphate (ATP) yield (sigma ATP)
      and anaerobic capacity (AC) were estimated from changes in metabolites in the
      vastus lateralis muscle and blood lactate concentration during the high intensity
      cycling session. The activities of glycogen phosphorylase, phosphofructokinase
      and citrate synthase, as well as muscle buffer value (in vitro beta) were also
      determined. The Y-int (kilojoules) was positively correlated (P < or = 0.05) with
      AC (r = 0.73), sigma ATP (r = 0.70) and in vitro beta (r = 0.71); similar
      correlations (P < or = 0.05) were observed for Y-int (joules per kilogram). The Y
      int was not correlated (P > 0.05) with any enzyme activity.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7713079
TI  - MR imaging in inferior vena cava thrombosis.
AB  - PURPOSE: To prospectively evaluate the efficacy of MR imaging in inferior vena
      cava (IVC) thrombosis; to differentiate acute from non-acute thrombus, and to
      identify the presence of changes in the morphology and signal intensity during
      medical treatment. METHODS AND MATERIALS: Seventeen patients with suspected IVC
      thrombosis underwent 30 MR examinations. The IVC thromboses were subdivided into
      two groups (acute and non-acute) according to onset of clinical symptoms. MR
      imaging of the IVC was analyzed and when an IVC thrombus was identified, a
      qualitative and quantitative assessment of the thrombus on spin-echo sequences
      with magnitude and phase reconstruction was performed to evaluate the
      relationship between signal intensity and the time elapse since the onset of
      clinical symptoms. Venography and/or CT scan proof was available in all cases.
      RESULTS: IVC thrombus was correctly identified in 19 MR examinations which showed
      the size, localization and the degree of lysis during follow-up. No differences
      were found in the signal intensity of the thrombus related to time. The pattern
      of the signal intensity was homogeneous in six (86%) acute thrombus and
      heterogeneous in nine (75%) thrombus of more than 1 week duration. A significant
      statistical relationship (P < 0.01) existed between the thrombus age and
      differences in the pattern of signal intensity. CONCLUSIONS: MR imaging is
      accurate to assess the localization and size of IVC thrombus, similar to the
      imaging techniques of reference. In addition, MR also provides useful information
      about the age and the morphological variations of thrombus during medical
      treatment.

PMID- 7713080
TI  - Retropharyngeal ganglioneuroma: ultrasound, CT and MRI findings in a 57-year-old
      patient.

PMID- 7713081
TI  - Muscular necrosis after retroperitoneal lymphadenectomy.

PMID- 7713082
TI  - Parasternal sonography of the internal mammary lymphatics in breast cancer: CT
      correlation.
AB  - The purpose of this study was to evaluate the efficacy of parasternal
      ultrasonography (US) in diagnosing internal mammary lymph node metastases in
      breast cancer, an important site of occult metastases, adversely affecting the
      disease-free interval and long-term survival. Thirty-five patients who were
      diagnosed with breast cancer were examined for internal mammary lymph node (IMLN)
      involvement with parasternal US, and results were correlated with computed
      tomography (CT). Longitudinal and transverse images of the first through sixth
      parasternal rib interspaces were evaluated with a 7.5-MHz linear-array
      transducer. The enlarged nodes were demonstrated as discrete, spherical or ovoid
      hypoechoic lesions in six cases with parasternal US, and corresponding CT scans
      confirmed the presence of lymphadenopathy. Our results suggest that parasternal
      US may be helpful in the evaluation of IMLN metastases in breast cancer as a part
      of staging the disease.

PMID- 7713083
TI  - Breast mass due to rib tuberculosis.

PMID- 7713084
TI  - Benign pulmonary leiomyomatosis with cyst formation and breast metastasis: case
      report and literature review.

PMID- 7713087
TI  - Low-field versus high-field MR imaging of the knee: a comparison of signal
      behaviour and diagnostic performance.
AB  - A prospective study was undertaken to compare MR imaging of the knee obtained
      with low-field and high-field systems. In 10 subjects, MR imaging of the knee was
      performed on a 0.2 T permanent magnet and on a 1.5 T superconductive system.
      Similar spin echo (SE) and 3D-FISP (3D Fourier transform with steady state
      precession) acquisitions were obtained. Comparative image analysis was performed
      independently by four radiologists. Results show that the image quality and
      diagnostic performance delivered by state-of-the-art 0.2 T and 1.5 T systems is
      equivalent. Advantages of the 1.5 T system included: better signal-to-noise
      ratio, shorter scan times, better visualization of asymptomatic grade 1 meniscal
      degeneration on SE images. Advantages of 0.2 T images were: decreased chemical
      shift, susceptibility and flow artifacts, improved evaluation of subchondral bone
      on 3D-FISP images, slightly better patient tolerance. We conclude that, for MR
      imaging of the knee, a low-field system is a cost-effective alternative to more
      expensive superconducting units.

PMID- 7713086
TI  - Computed tomography dacryocystography.
AB  - Twenty-one patients with epiphora were examined by conventional
      dacryocystography, using Lipiodol as a contrast medium, and CT dacryocystography,
      using a water soluble contrast medium. In the latter, the material was not
      introduced under pressure but three or four drops were administered, providing a
      physiological method of investigation. Subsequently, CT dacryocystography
      provides functional information about lacrimal disorders and is easy to use.

PMID- 7713085
TI  - The role of CT and MRI in the investigation of orbital roof fractures.

PMID- 7713088
TI  - Esophageal peridiverticulitis: an unusual complication of esophageal intramural
      pseudodiverticulosis.

PMID- 7713089
TI  - Role of shoulder ultrasonography in the evaluation of the painful shoulder.
AB  - The purpose of this study was to determine the accuracy of ultrasonography in the
      detection of rotator cuff tears. In a prospective study of 41 patients, the
      ultrasound results could be compared with the combined results of (CT)
      arthrography, arthroscopy and operation. The sensitivity of sonography in
      detecting partial and total rotator cuff tears was 86%, the specificity 91%, the
      positive predictive value 96% and the negative predictive value 73%. In spite of
      the relatively small size of this series, our results are comparable with those
      of most other studies. Based on these results, sonography can provide a non
      invasive, rapid and inexpensive diagnostic method for screening patients with
      shoulder complaints. A disadvantage of the method is its long learning curve.

PMID- 7713090
TI  - Remote expert consultation for MRI procedures by means of teleradiology.
AB  - From April 1992 to January 1993, radiology expert opinion for MRI procedures was
      offered by means of teleradiology. The experiment was carried out in addition to
      an existing service of a mobile MRI unit. MRI images were sent by means of
      teleradiology via regular telephone lines from the mobile MRI unit to an academic
      hospital, which served as expert consultation centre. During this period, 43
      requests for expert opinions were performed. This article describes the clinical
      effects of these expert opinions, and the technical and organisational
      requirements to perform teleradiology in daily clinical practice.

PMID- 7713091
TI  - Non-selective digital subtraction angiography in comparison with selective
      conventional angiography in the diagnosis of carotid artery disease.
AB  - In the recent past, non-selective arterial digital subtraction angiography
      (NSDSA) seemed a less invasive alternative to conventional filmscreen angiography
      (CFA) in the diagnosis of carotid artery disease. NSDSA obviated the need for
      selective catheterization with its associated risks but yet took advantage of the
      DSA method. However, this technique has not found general application although
      there are no reports that formally assess the (dis)advantages of NSDSA. The aim
      of our study was to compare the reliability of NSDSA with CFA in evaluation of
      carotid bifurcations in patients with transient ischemic attacks or partial
      stroke by reviewing prospectively collected data. Over a 2-year period, 40
      patients (upper age limit 65 years) underwent both NSDSA and CFA. Bilateral NSDSA
      was performed in all 40 patients (80 bifurcations). Bilateral CFA was performed
      in 27 patients whereas unilateral CFA was carried out in 13 patients (67
      bifurcations). Inter- and intra-observer variability for the degree of stenosis
      was determined by calculation of kappa-values for a 4-point and a 2-point scale.
      The proportion of interpretable studies was significantly lower in NSDSA. The
      inter- and intra-observer agreement was on average better in CFA examinations,
      though the difference was only statistically significant for the inter-observer
      agreement. The results of our study indicate that images obtained with NSDSA give
      less reliable information about carotid artery disease than images obtained with
      CFA. This is in accordance with the fact that NSDSA now seems an abandoned
      technique.

PMID- 7713092
TI  - Diagnostic performance of digital subtraction angiography (DSA) and magnetic
      resonance angiography (MRA): preliminary results in vascular occlusive disease of
      the abdominal and lower-extremity arteries.
AB  - Fifty-nine patients with occlusive disease of the aorto-iliac and femoro
      popliteal arteries were investigated prospectively by intravenous (IV) or
      intraarterial (IA) digital subtraction angiography (DSA) and magnetic resonance
      angiography (MRA). This was accomplished using a two-dimensional (2D) Inflow- (59
      patients) and a 2D Phase Contrast- (RSE--rapid sequential excitation) sequence
      (29 patients). The spectrum of pathology included stenoses < 50%, stenoses 50
      89%, stenoses 90-99%, occlusions, aneurysms and status following reconstructive
      surgery. MRA- and DSA-examinations were evaluated by four radiologists. The
      diagnoses were made by consent decisions of a radiologist and a vascular surgeon
      based on clinical and radiological findings. Diagnostic performance of IA-DSA was
      superior to all other imaging modalities. Vascular delineation of 2D Inflow-MRA
      was comparable to that of IV-DSA. The image quality of RSE-MRA was not adequate
      for diagnosis. In conclusion, 2D Inflow-MRA is a promising method for evaluating
      abdominal and peripheral arteriosclerotic disease. Interpretation of MR
      angiograms, however, requires profound knowledge of MRA-techniques, X-ray
      angiography and hemodynamics.

PMID- 7713095
TI  - Portal vein reconstruction based on topology.
AB  - Traditionally the intrahepatic vascular anatomy is correlated to the segment
      anatomy of the liver for which--following Couinaud [1]-the portal vein has been
      accepted as a guiding structure. This paper proposes a new method for the
      extraction and 3D-visualization of the portal vein based on Spiral CT data.
      Starting from a seed voxel, the algorithm expands stepwise within the structure
      of interest. Bifurcations are recognized and a symbolic tree is generated
      simultaneously which allows for interactive identification of sub-branches, their
      selection and specific colouring. The method is able to extract at least three
      generations of branches of the portal vein. A volume renderer is used to
      visualize the reconstructed portal vein superimposed to a transparent view of
      liver tissue and focal lesions. This provides a new tool for the planning of
      segment-oriented liver surgery (e.g. localization of lesions relative to the
      portal vein). But the method promises also to be useful for other applications,
      e.g. comparative studies of liver anatomy and pathology, or portosystemic shunt
      operations--TIPS (transjugular intrahepatic portosystemic shunts).

PMID- 7713094
TI  - The acute effect of ioversol on kidney function: role of endothelin.
AB  - The effect of ioversol, a non-ionic monomer with high hydrophilicity, on renal
      function was studied using the isolated perfused rat kidney (IPRK). The
      involvement of endothelin in the renal effect of ioversol was established
      pharmacologically using the selective endothelin ETA receptor antagonist BQ123.
      Ioversol 20 mgI/ml produced a sustained fall in both renal perfusate flow (RPF)
      and the glomerular filtration rate (GFR) together with a fall in sodium
      reabsorption (FRNa) and increase in urine flow (n = 6). In the presence of BQ123
      (10 microM), the effect of ioversol 20 mgI/ml on GFR was completely abolished and
      the fall in RPF and FRNa markedly reduced (n = 6). These results suggest that
      effect of ioversol on renal haemodynamics in the IPRK is mediated by endothelin.
      Ioversol produced a significantly smaller decrease in GFR than iopromide, a
      contrast media with similar osmolality but lower hydrophilicity, when compared to
      a previous study using an identical experimental technique. Increased
      hydrophilicity may therefore present an advantage for ioversol, reducing its
      effects on renal function.

PMID- 7713093
TI  - The significance of coumarin anticoagulation in laser assisted percutaneous
      transluminal angioplasty of femoropopliteal arterial obstructions.
AB  - The optimal regime of drugs to prevent thrombocyte aggregation leading to
      reocclusion after percutaneous transluminal angioplasty (PTA) of peripheral
      vessels is not established. Both antiplatelet and antithrombotic drugs are
      prescribed. Prospective observations of two different anticoagulation regimes
      were made during an ongoing multicenter study of laser-assisted PTA (PTLA) of the
      femoropopliteal artery. Group I (129 patients) received coumarin at least during
      the first month, Group II (n = 71) did not get oral anticoagulation. Seventy
      eight patients (61%) in Group I and 29 patients (47%) in Group II received
      platelet inhibitors. Groups I and II did not differ in baseline characteristics
      and PTLA complications (20.9 vs. 18.2%). Ankle brachial indices at 1, 3, 6 and 12
      months were similar in both groups. This observational study does not provide
      evidence for superiority of oral anticoagulation in the management of patients
      undergoing PTLA of the femoropopliteal tract.

PMID- 7713097
TI  - Heart failure: clinical aspects from basic research. 9-11 December 1993, Berlin,
      Germany. Proceedings.

PMID- 7713096
TI  - Heart failure: clinical aspects from basic research. Introduction.

PMID- 7713098
TI  - Cloning, expression and regulation of angiotensin II receptors.
AB  - Angiotensin II isoform 1 (AT1) receptor cDNAs were cloned by expression cloning
      from bovine adrenal and rat vascular smooth muscles. Human AT1 receptor was also
      cloned. Seven transmembrane structures emerged. A single type of receptor seems
      to interact with more than one type of G-protein. AT1 consists of subtypes AT1A
      and AT1B, and the regulation of the receptors occurs at many stages. The isoform
      AT2 was also expression cloned from rat pheochromocytoma cells. Although its
      ligand binding is not affected by GTP analogs, it is a seven transmembrane domain
      receptor. It mediates the inhibition of phosphotyrosine phosphatase by
      angiotensin II and AT2 specific CGP42112A; the inhibition was abolished by
      pertussis toxin. Thus, AT2 belongs to a new class of angiotensin receptors with
      unique signalling and regulatory mechanisms.

PMID- 7713099
TI  - Genetic polymorphisms of the angiotensin II type 1 (AT1) receptor gene.
AB  - Numerous essential, physiological effects on the cardiovascular system are
      attributable to angiotensin II (Ang II). Because of this we can assume that
      genetic changes in the specific receptor of Ang II (Ang II type 1 receptor gene,
      AT1) play a decisive role in the occurrence of cardiovascular disease associated
      with blood pressure regulation, vascular tone, cardiac and vascular growth
      process. To test this hypothesis, we examined the presence of polymorphisms
      within the coding region of the AT1 gene using polymerase chain reaction (PCR)
      and subsequent non-radioactive sequencing of samples from a control group with no
      previous history of cardiovascular complaint in individuals or immediate family.
      Using the Taq-sequencing procedure we found polymorphic sites, especially in the
      5' region of the gene (base pair positions 9, 16, 87, 133, 186), two of which led
      to an exchange of the amino acid (amino acid 6: Ser<==>Pro, amino acid 45:
      Gly<==>Arg). Together with the silent polymorphism at base pair position 573,
      which our group established previously, an additional polymorphism in the 3'
      region of the gene was discovered. This, however, did not confer any changes in
      amino acid sequence. In a preliminary study we found no association between the
      distribution of the C/T573 polymorphic site and cardiovascular disease, such as
      essential hypertension (n = 20) coronary artery disease (n = 16) hypertrophic
      cardiomyopathy (n = 12) or dilated cardiomyopathy (n = 21). Further studies will
      be needed to determine to what extent the polymorphisms described are associated
      with cardiovascular disease.

PMID- 7713100
TI  - Dose-related effects of ACE inhibition in man: quinapril in patients with
      moderate congestive heart failure. The Study Group on Neurohormonal Regulation in
      Congestive Heart Failure: Lausanne, Switzerland; Berlin, Dusseldorf, Munich,
      Germany.
AB  - Early treatment with ACE inhibitors of even moderate heart failure is clinically
      beneficial, even though haemodynamic measurements cannot adequately quantitate
      such improvement. Neurohumoral assessment is, however, supposed to be more
      accurate. In 55 patients with moderate heart failure (ejection fraction < or =
      35%), we investigated the dose-dependent effects of ACE inhibition with quinapril
      taken orally (2.5, 5 or 10 mg b.i.d.) following a placebo-controlled, parallel
      design protocol over 12 weeks. Plasma components of the renin angiotensin system,
      catecholamines and ANF were measured together with haemodynamics both at rest and
      during exercise. Before ACE inhibitor treatment, median PRA, Ang I and II and
      catecholamines were normal, while ANF was increased. All these parameters,
      including ACE activity, rose during exercise. Chronic inhibition of ACE activity
      was dose-dependent and the maximal fall in Ang II occurred with quinapril 20
      mg.day-1. Humoral changes appeared more assessible than haemodynamic alterations
      even though many of these changes were reasonably correlated. The effects of
      chronic ACE inhibition on circulating neurohumoral components in patients with
      moderate heart failure are small and dose-dependent. Since humoral changes are
      related to haemodynamics they should account for the clinical benefit.
      Appropriately high doses of ACE inhibitors should be chosen for treatment of
      heart failure.

PMID- 7713101
TI  - Dose-response relationships of ACE inhibitors and angiotensin II blockers.
AB  - It is difficult to establish dose-response relationships for ACE inhibitors in
      patients with hypertension or congestive heart failure. This has led to the
      widely held opinion that the effects of ACE inhibitors are hardly dose dependent.
      The purpose of this short discussion is to demonstrate that this class of
      compounds, as well as the more recent angiotensin II receptor antagonists,
      exhibit some very clear dose-response relationships when these are evaluated in
      normal volunteers based on the mechanisms for which they were designed.
      Characterization of these dose-response curves is important in order to use these
      drugs at their optimal dose and to obtain the maximal therapeutic benefit.

PMID- 7713102
TI  - Therapeutic strategies and neurohormonal control in heart failure.
AB  - Neurohormonal activation is one of the major determining factors in the process
      of transition from asymptomatic ventricular dysfunction to end-stage heart
      failure, in the prognosis of heart failure, and in the efficacy and, hence,
      choice and timing of pharmacological therapy. Although various counteracting
      hormonal systems are involved, emphasis in terms of functionality is on
      vasopressor and growth-promoting systems. In contrast, ANF and N-terminal proANF
      probably have a significant prognostic value, even at an early stage. The focus
      of heart failure therapy is moving from measures aimed at improving cardiac
      function to ones that concentrate on modulating neuroendocrine changes during
      failure and their effects on intrinsic peripheral and cardiac alterations.
      Although ACE inhibition undoubtedly constitutes a major step forward in this
      approach, alternative ways to modulate neurohormonal activation pharmacologically
      are needed. Several such novel approaches are being developed, including
      angiotensin receptor antagonists, dopaminergic stimulation, neutral endopeptidase
      inhibition, aldosterone antagonism and beta blockade. In addition to their
      positive inotropic properties digitalis glycosides may act as neurohormonal
      modulators. Finally, the realization that several well-established forms of heart
      failure therapy may aggravate neuroendocrine stimulation demands careful
      consideration as to whether such agents are really necessary, and underlines the
      desirability of co-administering neurohormonal modulating therapy.

PMID- 7713103
TI  - Losartan in heart failure: preclinical experiences and initial clinical outcomes.
AB  - Losartan potassium (Cozaar) is an angiotensin II receptor antagonist (AT1
      selective) which has undergone extensive clinical trials for the treatment of
      hypertension. This literature survey will review some of the pre-clinical
      findings with losartan in models of heart failure, and where appropriate, we will
      compare the haemodynamic findings in animals with similar studies completed in
      patients. The major conclusion from these trials is that losartan has clear
      haemodynamic benefits in patients in heart failure and that the drug appears to
      be well tolerated, with a low incidence of adverse experiences related to
      impaired renal function.

PMID- 7713104
TI  - Metabolic tissue characterization in the failing heart by positron emission
      tomography.
AB  - Congestive heart failure represents an important clinical issue which can benefit
      from newer imaging approaches. Use of radiolabelled pharmaceuticals allow for
      functional tissue characterization in patients with impaired left ventricular
      function. Assessment of regional myocardial perfusion and metabolism with either
      SPECT or PET methods provide accurate detection of tissue viability. Several
      studies have indicated the utility of these imaging approaches for improved
      selection of patients for revascularization. The combination of functional
      measurements with echocardiography and metabolic tissue characterization with PET
      allows for the non-invasive measurement of cardiac efficiency. The effect of
      various therapeutic interventions can be objectively assessed by a work-metabolic
      index. Finally, autonomic innervation of the heart plays an important role in the
      modulation of the haemodynamic performance of the failing heart. New imaging
      approaches using radiolabelled catecholamine analogues or receptor antagonists
      have been used to identify the integrity of myocardiac pre- and post-synaptic
      sympathetic innervation. Imaging results in patients with dilated cardiomyopathy
      not only demonstrated a down-regulation of beta-receptor density, but also an
      abnormal pre-synaptic neuronal function, which may result into impaired
      regulation of extraneuronal catecholamine concentration. Thus, advanced
      scintigraphic imaging approaches may improve our diagnostic and prognostic workup
      in patients with congestive heart failure and may provide objective endpoints for
      the assessment of therapy.

PMID- 7713105
TI  - Biochemical and electrophysiological alterations underlying ventricular
      arrhythmias in the failing heart.
AB  - Our understanding of the electrophysiological and biochemical mechanisms
      underlying malignant ventricular arrhythmias in the setting of heart failure has
      been limited, in large part because of the lack of experimental preparations of
      heart failure that demonstrate spontaneously occurring ventricular arrhythmias.
      Recent 3-dimensional cardiac mapping studies in experimental preparations of
      heart failure, as well as the failing human heart, have demonstrated that focal
      non-reentrant mechanisms may underlie ventricular tachycardia occurring
      spontaneously or induced by programmed electrical stimulation. This non-reentrant
      activation may be due to triggered activity arising from delayed after
      depolarization. Alterations of calcium homeostasis in the failing heart involving
      a number of ionic channels and membrane transporters may contribute to increased
      levels of intracellular calcium and the activation of a transient inward current.
      Modulation of calcium flux by alpha- and beta-adrenergic stimulation may impact
      significantly on development of arrhythmias in the failing heart. Activation of
      the renin-angiotensin system and the generation of free radicals may also
      contribute. A thorough understanding of the underlying electrophysiological and
      biochemical alterations responsible for arrhythmogenesis in the failing heart
      will be critical for the development of therapeutic agents to prevent sudden
      death in patients with congestive heart failure.

PMID- 7713106
TI  - Clinical significance and management of ventricular arrhythmias in heart failure.
AB  - Ventricular arrhythmias are a frequent finding in patients with heart failure,
      and heart failure is a major underlying condition which is correlated to sudden
      death. Therefore, both sudden death and death from progression of heart failure
      strongly overlap. Besides long-term ECG recording, newer diagnostic techniques
      have been developed. The prognostic significance of the signal-averaged ECG in
      patients with advanced left ventricular dysfunction in the presence of coronary
      artery disease has been demonstrated; however, in patients with dilated
      cardiomyopathy, signal-averaging for detection of late potentials has not yet
      been clearly established as a useful diagnostic tool. Furthermore, heart period
      variability has been shown to correlate to overall mortality but not to a
      specific mechanism. Finally, programmed ventricular stimulation, though useful in
      patients with left ventricular dysfunction and/or heart failure in the setting of
      coronary artery disease, is of questionable significance in patients with dilated
      cardiomyopathy. With increasing degrees of left ventricular dysfunction, the
      efficacy of antiarrhythmic drugs decreases. On the other hand, with increasing
      degrees of heart failure, antiarrhythmic drugs demonstrate a greater negative
      inotropic effect, more frequent proarrhythmic effects, and more frequent
      bradyarrhythmias. Currently, several ongoing amiodarone trials are assessing
      different approaches of antiarrhythmic treatment in patients with heart
      failure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713107
TI  - Differentiation between systolic and diastolic dysfunction.
AB  - Left ventricular (LV) failure can be divided into systolic and diastolic
      dysfunction. The former is characterized by a reduced ejection fraction and an
      enlarged LV chamber, the latter by an increased resistance to filling with
      increased filling pressures. Systolic dysfunction is clinically associated with
      left ventricular failure in the presence of marked cardiomegaly, while diastolic
      dysfunction is accompanied by pulmonary congestion together with a normal or only
      slightly enlarged ventricle. Echocardiography is currently the most relevant
      technique for non-invasive differentiation of the two forms. Systolic dysfunction
      is easily assessable by estimation of global ejection fraction and regional wall
      motion. Diastolic dysfunction can be diagnosed indirectly by means of a normal or
      nearly normal ejection fraction and and changes of the mitral filling pattern in
      the context of LV failure. For an exact determination of diastolic dysfunction LV
      catheterization is required. Systolic dysfunction treatment is well defined,
      consisting of ACE inhibitors, followed by diuretics and digitalis. Calcium
      channel blockers are usually contraindicated. Diastolic dysfunction therapy is
      more dependent on the underlying disease. Calcium channel blockers, ACE
      inhibitors or beta-blockers are first line drugs in most instances: diuretics can
      be added with increasing symptoms. Digitalis should be avoided, except in atrial
      fibrillation, to control heart rate.

PMID- 7713108
TI  - Identification of gene defects by linkage analysis: use in inherited
      cardiomyopathies.
AB  - One of the central activities of current medical (including cardiological)
      research is identification of the causes of inherited diseases. The goals are the
      determination of genes and risk factors, introduction of new diagnostic standards
      and ultimately refinement of therapies. In cardiac disorders, molecular causes
      have been detected for certain types of hypertrophic cardiomyopathy (HCM), a
      disease characterized by increased ventricular wall thickness, a high risk of
      arrhythmias and an increased frequency of sudden cardiac death. The first known
      cause of HCM was a point mutation in the cardiac beta-myosin heavy chain gene on
      chromosome 14, detected using a genetic mapping procedure based on linkage of the
      clinical phenotype with genomic marker sequences. Additional missense mutations
      have been located in the globular head of beta-myosin, and other disease loci
      have been identified on chromosomes 1, 11, and 15; the disease genes in these
      loci have not yet been determined, however.

PMID- 7713109
TI  - Angiotensin I converting enzyme gene: regulation, polymorphism and implications
      in cardiovascular diseases.
AB  - Angiotensin I converting enzyme (ACE), also called dipeptidyl-carboxypeptidase I
      (DCP I), is a zinc metallopeptidase widely distributed on the surface of
      endothelial and epithelial cells. Its role in the vasoactive peptide, the
      metabolism of the two active peptides, angiotensin and bradykinin, and the
      beneficial effects of its inhibition in cardiovascular diseases, have raised
      considerable interest in this enzyme. The potential implications of ACE gene
      polymorphism, which affects the expression of the gene in cardiovascular
      diseases, has been widely investigated. This review summarizes the results of
      these studies.

PMID- 7713110
TI  - Quantification of beta-adrenoceptors and beta-adrenoceptor kinase on protein and
      mRNA levels in heart failure.
AB  - The alterations of the beta-adrenoceptor adenylyl cyclase are reviewed. In
      failing myocardium, the down-regulation of beta 1-adrenoceptors is accompanied by
      a decrease in steady state mRNA levels, as studied with quantitative polymerase
      chain reactions in dilated and ischaemic cardiomyopathy. The density of beta 2
      adrenoceptors and beta 2-adrenoceptor mRNA was unchanged in both pathological
      conditions compared to non-failing myocardium. In addition to down-regulation of
      beta 1-receptor protein and mRNA, an increased activity of the beta-adrenoceptor
      kinase (beta-ARK) was observed. Correspondingly, quantification of beta-ARK mRNA
      by a 5' and a middle portion PCR-product suggests that increased enzyme activity
      could be due to increased transcription. In summary, decreased steady state
      levels of beta 1-adrenoceptor mRNA could contribute to reduced beta-adrenoceptor
      density in failing myocardium. The known uncoupling of beta-adrenoceptors could
      be due to an increased mRNA expression and activity of beta-ARK.

PMID- 7713111
TI  - Contractile function and response to agonists in myocytes from failing human
      heart.
AB  - Ventricular myocytes from failing human hearts have a similar maximum contraction
      amplitude in high Ca2+ to those from non-failing heart at low stimulation rates
      (0.2 Hz, 32 degrees C), but do not exhibit the same positive frequency-interval
      relationship. At higher stimulation rates (1 Hz) therefore, the amplitude is
      depressed in cells from failing hearts compared to controls. Slow relaxation is
      seen in myocytes from failing ventricle at all stimulation rates, and contraction
      velocity is also slightly reduced. beta-adrenoceptor desensitization is evident,
      and increases with severity of disease. There is also a post-receptor defect in
      myocytes from failing heart since responses to forskolin and cyclic AMP analogues
      are reduced, and this is accompanied by decreased cyclic AMP levels in myocardium
      from patients in end-stage disease. Pertussis toxin treatment, which inactivates
      Gi, reverses most of the alterations in the beta-adrenoceptor pathway. The role
      of the sympathetic system is indicated by the parallels between myocytes from
      failing human heart and those from the noradrenaline-treated guinea-pig, which
      show beta-adrenoceptor desensitization, a post-receptor defect and reduced basal
      cyclic AMP levels. However, relaxation velocities are not slowed in these guinea
      pig myocytes, indicating that basal cyclic AMP does not have a tonic role in
      speeding relaxation.

PMID- 7713112
TI  - Characterization of myocardial protein composition in dilated cardiomyopathy by
      two-dimensional gel electrophoresis.
AB  - In order to identify alterations in the myocardial protein pattern that
      characterize dilated cardiomyopathy (DCM), we compared, by two-dimensional gel
      electrophoresis, right atrial protein patterns from five patients with DCM and
      four with normal left ventricular function (two gels per patient). Using computer
      assisted analysis (PDQUEST, 4.1) we found reproducible protein patterns in the 18
      gels (23 x 30 cm, pH 4-9, molecular weight 10-150 kDa). In the two gels from the
      same patient, 91% of proteins were identical in their position in the pattern and
      the relative intensities of these protein species correlated with r = 0.85. Three
      hundred and two +/- 50 protein species were found in several gels, 186 in all 18
      gels. Seven proteins in the DCM group were decreased in their relative intensity
      by > 100%, six were increased by > 100%. Significant quantitative differences
      between DCM and control patients were found for 25 protein species. Based on
      seven external marker proteins, a pH and molecular weight value could be
      calculated for each protein. So far, 30 protein species have been identified by
      antibodies, amino acid analysis or sequencing procedures. From the 25 proteins
      that are significantly different between DCM and controls, three have been
      identified. Expression of the mitochondrial creatine kinase and alpha cristallin
      B chain was significantly increased in DCM; the malate dehydrogenase family was
      also significantly decreased in DCM. Two-dimensional electrophoresis appears to
      be a powerful method for the detection of disease-associated alterations in the
      myocardial protein pattern.

PMID- 7713113
TI  - Regulation of the structural remodelling of the myocardium: from hypertrophy to
      heart failure.
AB  - The Framingham heart study has shown that arterial hypertension is the major
      aetiological factor for the development of heart failure. In the presence of
      heart failure, various regulatory systems may be operative. These include the
      Frank-Starling mechanism, the neurohormonal system, regulation of cardiac growth
      and peripheral oxygen delivery. Recently, the interrelationship of the
      neuroendocrine system and cardiac growth has been examined. In the pressure or
      volume overloaded heart, growth of the myocardium involves the enlargement of
      cardiac myocytes, an adaptation governed by ventricular loading. Non-myocyte cell
      growth, including cardiac fibroblasts, may also occur. However, the haemodynamic
      load does not appear to be its major physiological stimulus. Cardiac fibroblast
      activation is responsible for the accumulation of type I and III collagens, the
      major fibrillar proteins of the myocardial collagen matrix, while vascular smooth
      muscle cell growth accounts for medial thickening of coronary resistance vessels.
      This structural remodelling of the cardiac interstitium represents a major
      determinant of pathological hypertrophy: it accounts for abnormal myocardial
      stiffness and impaired coronary reserve, thereby leading to ventricular diastolic
      and systolic dysfunction and ultimately the appearance of symptomatic heart
      failure. Several lines of evidence suggest that circulating and tissue renin
      angiotensin-aldosterone systems are involved in the structural remodelling of the
      non-myocyte compartment, including the 'cardioprotective' effects of angiotensin
      converting enzyme (ACE) inhibition or the beneficial effects of anti-aldosterone
      treatment that were found to prevent myocardial fibrosis in renovascular
      hypertension due to unilateral renal ischaemia under experimental
      conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713114
TI  - Gap junction alterations in the failing heart.
AB  - Electrical and mechanical integration between myocytes is mediated by three types
      of intercellular junction, the fascia adherens, desmosome and gap junction. Gap
      junctions are responsible for electrical coupling, and consist of clusters of
      plasma membrane channels that directly link the cytoplasmic compartments of
      neighbouring cells. Each channel consists of two hemichannels (connexons; one
      from each plasma membrane) aligned across the narrow extracellular gap, and each
      hemichannel is constructed from six connexin molecules. Using specific
      anticonnexin43 antibodies for immunofluorescence localization in combination with
      confocal laser scanning microscopy, alterations in the expression of connexin43
      gap junctions have been investigated in chronic ischaemic heart disease and heart
      failure due to ischaemic cardiomyopathy. Two major alterations are apparent: (1)
      disturbance in the spatial distribution of gap junctions at the border zone of
      healed infarcts, and (2) reduction in the quantity of immunodetectable connexin43
      in regions of normal gap junction distribution distant from infarct scars. These
      changes are likely to contribute to electromechanical dysfunction in ischaemic
      heart disease and heart failure, and appear to form part of a wider pattern of
      altered expression of different connexin types in the diseased heart.

PMID- 7713115
TI  - Phenotypic determinants of heart rate variability in cardiac hypertrophy and
      failure.
AB  - Reduced heart rate variability (HRV) has a strong predictive value in terms of
      sudden death, as compared to other prognostic criteria, but it has never been
      previously studied in experimental models of cardiac hypertrophy and failure.
      However, it has been quantified in rats using Holter monitoring and the peak and
      trough method of analysis. In normal rats, as in humans, short and long
      oscillations, sensitive, respectively, to atropine and propranolol were detected.
      Both correlate with heart rate. Cardiothyrotoxicosis was characterized by
      tachycardia and, independently, by a pronounced alteration in long oscillations.
      HRV was normal in compensatory cardiac hypertrophy due to aortic stenosis, but in
      this model the normal correlation existing between HRV and heart rate had
      disappeared. It is suggested that the main determinants of the above
      modifications of HRV are the changes in the new myocardial phenotype observed in
      terms of beta-adrenoceptor and muscarinic densities.

PMID- 7713117
TI  - Tissue angiotensin II system in the human heart.
AB  - Several intervention studies with angiotensin I converting enzyme (ACE)
      inhibitors have demonstrated a remarkable improvement in the treatment of
      patients with primary hypertension and congestive heart failure. Since ACE
      inhibitor therapy in patients with congestive heart failure not only improves
      systemic haemodynamics but also provides a better prognosis, the cardiac renin
      angiotensin system is apparently one of the major targets of ACE inhibitor
      therapy. Recent studies provided evidence that the human heart contains high
      affinity Ang II (Ang II) receptors with both subtype population and ACE. In
      addition to ACE, a novel cardiac Ang II forming enzyme (human chymase) has been
      identified in human hearts. Unlike in the rat heart, the minor (10%) component of
      Ang II-forming activity in the left ventricle is due to ACE, whereas the major
      (80%) component is due to human chymase. This novel cardiac serine proteinase has
      been purified from the human left ventricle and characterized, and recently, the
      cDNA and the gene for this enzyme have been cloned. Biochemical characterization
      revealed that human chymase is the most efficient and specific Ang II-forming
      enzyme described thus far, but the cellular and regional distribution of the two
      Ang II-forming enzymes seems to be different. ACE is mainly localized in
      endothelial cells and fibroblasts and the expression level is higher in atria
      than ventricles, whereas chymase is synthesized and stored in secretory granules
      of mast cells, endothelial cells, and mesenchymal cells, and after its secretion
      localized in the interstitial region of the myocardium and its expression is
      higher in ventricles than atria. These results imply distinct roles of these two
      Ang II-forming enzymes in cardiac Ang II formation and in the physiological
      function of the human heart. Since localization of cardiac renin and
      angiotensinogen were also identified in human heart, it is important to
      understand the detailed mechanisms of the tissue Ang II formation and its
      contribution to the pathophysiological changes in cardiovascular diseases.

PMID- 7713116
TI  - Activation of the renin-angiotensin system in heart failure and hypertrophy-
      studies in human hearts and transgenic rats.
AB  - Numerous in vitro studies have demonstrated that angiotensin II has distinctive
      cellular effects in the cardiovascular system, independent from its effects on
      blood pressure. These have led to the hypothesis that activation of the
      angiotensin system in the heart could be of functional relevance for the adaptive
      processes in several cardiovascular disorders, such as cardiac hypertrophy and
      heart failure. This concept has been supported by clinical studies showing the
      beneficial effects of blockers of the system such as angiotensin converting
      enzyme (ACE) inhibitors in these circumstances. In order to study the regulation
      of gene expression of renin angiotensin system components in cardiac disorders we
      have performed two studies. First, we investigated the gene expression of ACE in
      human heart failure. Results showed that the enzyme is activated locally in this
      condition, supporting previous studies in animals. Second, in a different
      approach, we asked whether the selective activation of the renin angiotensin
      system in the hearts of transgenic rats expressing an additional renin gene leads
      to the development of pathological changes in the cardiovascular system. The
      results of this study demonstrated that the transgenic animals developed cardiac
      hypertrophy and heart failure independent of the increase in blood pressure seen
      in these rats. Taken together, these studies provide further evidence for the
      functional role of local angiotensin systems in the heart.

PMID- 7713118
TI  - Myocardial cyclic AMP and norepinephrine content in human heart failure.
AB  - Impaired production of myocardial cyclic adenosine monophosphate (cAMP) is
      thought to contribute to contractile dysfunction in end stage heart failure, but
      myocardial cAMP content has not yet been evaluated in heart failure patients in
      comparison with controls. We therefore measured the myocardial content of cAMP by
      radioimmunoassay in endomyocardial biopsies from patients in different stages of
      heart failure and in controls and correlated it with biochemical and functional
      parameters. The myocardial content of norepinephrine was determined by HPLC in
      the same biopsies in order to assess if the myocardium studied was affected by
      heart failure. Myocardial cAMP (in fmol.microgram-1 non-collagen protein) in 20
      patients with heart failure (LVEF: 27 +/- 8%, cAMP: 5.8 +/- 2.0) was unchanged in
      comparison with eight controls (LVEF: 64 +/- 4.7%, cAMP, 4.9 +/- 2.1). In
      contrast, myocardial norepinephrine (in pg.microgram-1 non-collagen protein) in
      the same biopsies was significantly reduced in heart failure (4.0 +/- 3.0) in
      comparison with the same controls (11.5 +/- 3.0, P < 0.0002). Plasma cAMP in 20
      heart failure patients (22.0 +/- 4.2 pmol.l-1) was not different from
      controls(22.0 +/- 7.8), whereas plasma norepinephrine was increased (heart
      failure: 460 +/- 257 pg.ml-1, controls 182 +/- 49, P < 0.001). Myocardial cAMP
      levels are indistinguishable from controls in human heart failure and therefore
      do not contribute to a further characterization of the cardiac adrenergic system
      in these patients. This is most likely due to the impossibility of obtaining
      biopsies with truly unstimulated adenylyl cyclase activity.

PMID- 7713119
TI  - Angiotensin II receptor subtypes: selective antagonists and functional
      correlates.
AB  - Angiotensin II (Ang II) receptor heterogeneity is currently defined by the new
      subtype-selective agents, losartan (AT1) and PD123177 (AT2). Although both
      subtypes have been cloned and sequenced, only the AT1 receptor has been shown to
      have an important physiological or pathophysiological role. AT1 and AT2 receptors
      are found in both normal and failing cardiac tissue. They are found on myocytes,
      endothelial cells, fibroblasts, coronary arterial smooth muscle cells, and
      peripheral sympathetic nerves. The AT1 receptors mediate virtually all of the
      effects of Ang II in myocytes even though cardiac tissue may contain over 50% AT2
      sites. In endothelial cells, functional responses are predominately AT1. In
      fibroblasts, preliminary data suggest that AT2 receptors may be involved in
      collagen synthesis. In isolated tissue, Ang II has a limited positive inotropic
      effect in atrial, but not in ventricular tissue, which is blocked by losartan.
      Ang II may also have a tonic effect on coronary artery resistance as angiotensin
      inhibitors can increase coronary flow. Both ACE (Ang II synthesis) inhibitors and
      Ang II receptor antagonists produce beneficial effects in experimental models of
      heart failure, suggesting Ang II is an important mediator of heart failure.
      Because ACE inhibitors also potentiate bradykinin and are non-specific inhibitors
      of Ang II synthesis (availability of Ang II to both receptor subtypes) some
      differences can be anticipated. At the present time, however, the beneficial role
      of bradykinin is controversial and the predominant functional Ang II receptor in
      the heart and other tissues is the AT1 subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713120
TI  - Functional significance of angiotensin receptors in human myocardium. Significant
      differences between atrial and ventricular myocardium.
AB  - We studied the effects of angiotensin (Ang) I and II in a variety of isolated
      human cardiac tissues contracting under physiological conditions (37 degrees C,
      60 beats.min-1). Ang I and II consistently increased the peak developed force of
      human atrial muscles by 30-40%, an effect that was completely blocked by 10(-6) M
      saralasine, but not by the combination of prazosin and propranolol. However,
      neither Ang I or II had significant inotropic effects in right and left
      ventricular human preparations. We were also able to demonstrate that the
      positive inotropic effect of Ang II in human right atrial tissue is mediated by
      the AT1 receptor subtype but not the AT2 receptor subtype.

PMID- 7713121
TI  - Regulation of the angiotensin receptor subtypes in cell cultures, animal models
      and human diseases.
AB  - With the development of subtype specific angiotensin II (Ang II) receptor
      antagonists and their introduction into the treatment of heart failure and
      hypertension, the regulation of the Ang II receptor with its subtypes AT1 and Ang
      T2 gains clinical importance. In cell cultures, the number of surface AT1 is
      clearly down-regulated by Ang II exposure. Down-regulation can be due to
      reversible internalization, to phosphorylation and to reduced synthesis and
      involves protein kinase C and phospholipase C mediated pathways. In this respect,
      the AT1 behaves as a typical G-protein coupled receptor. Aldosterone, cAMP,
      norepinephrine and extracellular glucose concentrations can contribute to AT1
      regulation. There are very few data regarding the regulation of the subtype AT2,
      indicating modulation by a number of growth factors and by Ang II. In whole
      animal models receptor regulation deviates partially from cell cultures. In the
      rat, the two subtypes AT1A and AT1B are differentially regulated and the
      expression of subtypes is organ specific. In most experiments, including our own
      experiences, the AT1, in the adrenals was up-regulated by Ang II infusion and
      down-regulated by angiotensin converting enzyme inhibitors (ACEI) or Ang II
      receptor antagonists. Differing effects were observed in other organs. In humans,
      a number of studies seeking an association between Ang II levels, Ang II receptor
      regulation and physiological events have been conducted in platelets. In pregnant
      women, a negative correlation between plasma Ang II levels and Ang II binding and
      an association between receptor regulation and pregnancy-induced hypertension has
      been described.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713122
TI  - Angiotensin II receptor subtypes and cardiac function.
AB  - All the components of the renin-angiotensin system have been identified in the
      heart including the angiotensin II receptor subtypes AT1 and AT2. In the normal
      human heart, there is a decreasing receptor density from the right atrium to the
      left ventricle. In right atrial membranes prepared from pathological hearts, the
      percentage of AT1 receptor decreases with the severity of cardiac dysfunction
      whereas that of AT2 receptor increases. Treatment of hypertrophic rats with AT1
      receptor antagonists inhibits cardiac hypertrophy and reverses the increase
      receptor density, indicating involvement of this Ang II receptor subtype. The
      role of the AT2 receptor is still largely unknown but it may be involved in cell
      growth and proliferation. The cloning of both AT1 and AT2 receptors as well as
      the availability of potent and selective antagonists will help us to understand
      better the functional role of Angiotensin II in cardiovascular disorders.

PMID- 7713123
TI  - Conservative approach to the management of prostate cancer. A critical review.
AB  - Conservative management of patients with early prostate cancer has received
      increased attention in recent years. While this approach allows patients to avoid
      the potential side effects associated with radiation therapy and radical
      prostatectomy, many men who live 10 years or longer will develop advanced disease
      with watchful waiting. These patients are likely to suffer significant morbidity
      due to local or distant cancer progression. Conversely, some patients who receive
      aggressive initial treatment for localized prostate cancer will also experience
      morbidity secondary to recurrent or progressive disease despite early attempts at
      curative therapy. Therefore, the need for further prospective study to evaluate
      the relative effectiveness and morbidity of conservative management in comparison
      with radiation therapy and radical prostatectomy is evident.

PMID- 7713124
TI  - Operative strategy in laparoscopic nephrectomy.
AB  - Nephrectomy is a debilitating procedure because of the trauma to the abdominal
      wall. Laparoscopy could be a solution in this matter. Four patients underwent
      laparoscopic nephrectomy. In 3 patients with renal cancer, the transperitoneal
      route was used in order to obtain quicker access to the hilus. In the fourth
      patient with benign disease, a retroperitoneal route was chosen. There was no
      morbidity or mortality. Mean hospital stay was 5 days. Laparoscopic nephrectomy
      is safe and effective. Larger series are needed for evaluation of the long-term
      results in the treatment or renal cancer.

PMID- 7713126
TI  - Laparoscopic ureterolysis for idiopathic retroperitoneal fibrosis.
AB  - Ureterolysis and subsequent intraperitonealization were performed
      laparoscopically in 2 patients with unilateral idiopathic retroperitoneal
      fibrosis. The operative procedure was easily accomplished, and the outcome was
      excellent in the patient who had a ureteral stricture of 2 cm in length, whereas
      the operation was technically more complicated with a prolonged operation time in
      the other patient who had a stricture more than 5 cm in length. The convalescence
      period after the operation was short in both cases. Laparoscopic ureterolysis is
      a less invasive alternative to conventional open surgery, particularly in
      patients with involvement of a unilateral ureter of short length.

PMID- 7713125
TI  - Endopyelotomy and pyeloplasty: face to face.
AB  - 46 symptomatic adult patients with documented ureteropelvic junction obstruction
      were treated with pyeloplasty (n = 23) or endopyelotomy (n = 23). Basic
      characteristics in both the groups were comparable. The technical aspects,
      complications and outcome, in the form of improvement in function and drainage
      patterns, were compared in both the groups. Endopyelotomy enjoyed the significant
      advantages of a shorter operating time and hospital stay, and obviously better
      cosmetic acceptance. The major complications in the endopyelotomy groups were
      related to external drainage and secondary infection in the form of fever,
      secondary hemorrhage and slippage of tubes in 44, 9 and 13% of cases,
      respectively. Complications associated with pyeloplasty were prolonged urinary
      leak, wound infection and urinary tract infection in 12, 17 and 22% of cases,
      respectively. Using 99Tc-DTPA diuretic scan, an improvement of more than 10% in
      split renal function could not be documented for any case from either group. In
      none of the patients did the function deteriorate either. Of all evaluable cases,
      only 1 in the pyeloplasty group showed a persistent obstructive pattern. The rest
      all demonstrated adequate drainage across the ureteropelvic junction. Overall in
      12 cases (8 pyeloplasty, 4 endopyelotomy) drainage could not be determined
      postoperatively due to poor radionuclide uptake. A nephrostogram and/or pressure
      flow study, however, demonstrated a nonobstructive pattern in all these patients.
      It is concluded that endopyelotomy scores over pyeloplasty with a shorter
      operating time and hospital stay. The complication rate and outcome following
      surgery, however, are comparable in both the groups. Using external drainage
      following endopyelotomy, early resumption of work, however, could not be
      obtained.

PMID- 7713127
TI  - Endourological treatment of lumbar and iliac ureteral stones. A comparative study
      of 49 cases.
AB  - The efficacy of the Lithoclast has been described extensively in the recent
      literature. However, to our knowledge, few articles have dealt with the safety of
      this technique. We present a retrospective study of 49 patients with stones of
      the lumbar and iliac ureter treated between 1989 and 1992 either by means of the
      Lithoclast (17 patients), by electrohydraulic shock waves (16 patients), or by
      trapping the stones in a wire stone basket (16 patients). The success rates were
      88% for the Lithoclast and wire stone baskets and 62% for electorhydraulic shock
      waves. The mean dimensions of the stones were 10 mm for the Lithoclast and
      electrohydraulic shock wave groups, and 7 mm for the wire stone basket group.
      Complications consisted of 7 ureteral lesions (2 cases with the Lithoclast, 4
      cases with electrohydraulic shock waves and 1 case with the wire stone basket)
      and 1 stripping of the lower ureter following stone extraction with a wire stone
      basket, which required open reimplantation. This study demonstrates the efficacy
      and safety of the Lithoclast for the treatment of large stones of the lumbar and
      iliac ureter.

PMID- 7713128
TI  - The 'stone clinic effect': myth or reality?
AB  - Sixty-six active recurrent stone formers (RSF), i.e., with at least one stone
      annually over 3 years prior to the first examination at our stone clinic, were
      retrospectively evaluated. All received specific drug metaphylaxis which was
      discontinued after 5.5 +/- 2.1 years (period 1). They were reclassified according
      to the above definition into active and inactive RSF and were then left on a
      general metaphylactic regimen with regular urological follow-up every 6 months
      (period 2). 32 patients observed these recommendations for 5.7 +/- 2.6 years
      (group 1), 34 did not. 20 of these 34 could be reexamined after 6.3 +/- 2.2 years
      (group 2). Group 1 comprised 10 active and 22 inactive, group 2 comprised 1
      active and 19 inactive RSF. While the recurrence rates among the inactive RSF of
      groups 1 and 2 decreased significantly during period 2, a statistically
      significant difference between them was not observed. Conversely, there was only
      a slight reduction of the recurrence rate in the active RSF. Both findings argue
      against a stone clinic effect. Interviews of the patients showed that stone
      formation was periodical for a mean of 12 +/- 8 years, after which it gradually
      faded out. This period is termed 'phase of regular stone formation' and appears
      to be an autonomous process that cannot usually be influenced by metaphylactic
      measures. This could explain the wide variability of reported success rates for
      the various metaphylactic regimens, as they would merely reflect the number of
      stone formers who are in their phase of regular stone formation.

PMID- 7713129
TI  - Multidisciplinary evaluation of diabetic impotence.
AB  - Patients referring to the Urology and/or Endocrinology Departments of Ankara
      Medical School with complaints of diabetes mellitus (DM) and related
      complications were evaluated during the last year. A detailed history was
      obtained and all of the patients were questioned especially about sexual function
      problems. Following this evaluation, all patients were divided into two main
      groups, i.e. patients with sexual disorders, and those with normal sexual
      function. Factors such as BPH, cerebrosclerosis and other important vascular
      neurologic pathologies which may play a role in the etiology of impotence were
      excluded from the study and 38 patients with sexual dysfunction and 15 with
      normal sexual activities have undergone further evaluation. Following routine
      blood and urine analyses, serum hormone levels (testosterone, FSH, LH, prolactin)
      were determined. Penile color-flow doppler analysis, cavernosometry,
      cavernosography, bulbocavernous reflex latency time and evaluation of
      somatosensory evoked potentials were performed. Additionally, all patients were
      evaluated from the psychiatric aspect using the Hamilton depression scale and
      MMPI questionnaire. The presence of vascular or neurologic pathology in 89.4% of
      our patients and of both pathologies in 39.4% of the patients, indicated the
      importance of multifactorial evaluation of diabetic impotence in order to plan a
      complete and efficient therapy program.

PMID- 7713130
TI  - Comparison of a mixture of papaverine, phentolamine and prostaglandin E1 with
      other intracavernous injections.
AB  - OBJECTIVE: evaluation of a self-injection program with a mixture of papaverine,
      phentolamine and prostaglandin E1 (PGE1). METHOD: a self-injection program for
      erectile dysfunction was started by 48 patients, using a 1-ml mixture of 4.5 mg
      papaverine, 0.2 mg phentolamine and 1.5 micrograms PGE1. Patients completed a
      questionnaire at 6 weeks and at 3 months and were followed at the Outpatients
      Department for an average of 1 year. RESULT: of these patients 25 had previous
      experience with 20 micrograms PGE1 for intracavernous use and 22 patients had
      previously used 30 mg papaverine with 1 mg phentolamine. None of these 3 self
      injection drugs is obviously superior in its ability to induce erections.
      Priapism occurred twice on a total of 1,290 injections. After 1-year follow-up, 4
      patients had developed problems with fibrosis of the corpora, 2 of whom had
      encountered this problem also in a previous self-injection program. CONCLUSION:
      this triple mixture has the disadvantage of causing fibrosis and priapism in
      susceptible patients.

PMID- 7713131
TI  - Microsurgical epididymovasostomy for obstructive azoospermia: factors affecting
      postoperative fertility.
AB  - Azoospermia due to epididymal obstruction can be treated by microsurgical
      epididymovasostomy with high patency rates. Twenty-four azoospermic patients with
      epididymal obstruction due to a variety of causes underwent 26 microsurgical
      epididymovasostomies. The overall patency rate following surgery was 80.8% and
      impregnation was achieved by 10 patients (41.7%). Factors affecting the
      postoperative impregnation rate were etiology and duration of obstruction.
      Patients with an obstruction for < or = 15 years, caused by epididymitis or post
      vasectomy epididymal blow-out, achieved a higher impregnation rate than the
      others (8 of 9 vs. 2 of 11, p = 0.0019). The motility of epididymal sperm or the
      presence of serum antisperm antibodies had no apparent effect on postoperative
      fertility. Microsurgical epididymovasostomy is particularly effective in patients
      with epididymitis or vasectomy patients with a short-term obstruction.

PMID- 7713132
TI  - Expression of multidrug resistance gene product (P-glycoprotein) in transitional
      cell carcinomas of the upper urinary tract.
AB  - We assessed the expression of P-glycoprotein, the product of the multidrug
      resistance gene, in 107 specimens from patients with transitional cell carcinoma
      of the upper urinary tract, using an immunohistochemical method with a polyclonal
      antibody. P-glycoprotein was expressed in 28 of 107 (26%) specimens. While P
      glycoprotein expression was not related to the grade or stage of these tumors,
      the incidence of P-glycoprotein in specimens with tumors which coexisted in renal
      pelvic and ureter is significantly higher than those with either renal pelvic or
      ureter tumor alone. In the patients with advanced upper urinary tract tumor who
      had adjuvant chemotherapy including at least one P-glycoprotein-transported drug
      (mdr regimen), overall survival of patients with P-glycoprotein-positive tumor
      was significantly shorter than that of patients with negative tumor. This pilot
      study demonstrates that P-glycoprotein can be expressed in one fourth of
      transitional cell carcinomas of the upper urinary tract and that P-glycoprotein
      expression serves as a prognostic indicator in patients with these tumors who are
      treated with mdr regimens.

PMID- 7713134
TI  - Iatrogenic femoral arteriovenous fistula as a cause of erectile dysfunction.
AB  - The authors present a unique case of impotence in a 65-year-old patient caused by
      an iatrogenic common femoral arteriovenous fistula. After surgical treatment of
      the fistula, there was a clear improvement of the erectile function.

PMID- 7713133
TI  - Transitional cell carcinoma of the renal pelvis and its expression of p53
      protein, c-erbB-2 protein, neuron-specific enolase, Phe 5, chromogranin, laminin
      and collagen type IV.
AB  - Expression of p53 protein, c-erbB-2 protein, neuron-specific enolase (NSE), Phe
      5, chromogranin, laminin and collagen type IV was studied by immunohistochemistry
      in formalin-fixed and paraffin-embedded specimens from 20 patients with renal
      pelvic carcinoma. Positive membrane-bound c-erbB-2 staining was not found in any
      case. Two tumors stained for p53 protein. Focal immunoreactivity for laminin was
      present in 55% and for collagen type IV in 80%. 25% of the cases were NSE
      positive. None of the tumors stained for Phe 5 or chromogranin. The results were
      compared with the clinical outcome and the immunohistological findings of p53
      protein and c-erbB-2 protein in 13 cases of bladder carcinoma in the same patient
      group. Four of the thirteen bladder cancer specimens, but only 2 of the 20 renal
      pelvic cancer specimens, expressed p53 protein. As for renal pelvic carcinoma, c
      erbB-2 protein was not expressed in bladder carcinoma. We conclude that p53 gene
      abnormalities may be of importance in the development of carcinoma in the renal
      pelvis and urinary bladder, but c-erbB-2 protein expression does not play a major
      role.

PMID- 7713135
TI  - Subcutaneous metastases after coelioscopic lymphadenectomy for vesical urothelial
      carcinoma.
AB  - The authors report an exceptional case of subcutaneous metastatic dissemination,
      located at the puncture points of a coelioscopic lymphadenectomy for a vesical
      urothelial carcinoma. Few cases of parietal metastasis have been described after
      coelioscopic check-up for gynaecological and digestive tumours. The onset of this
      new type of serious complication suggests a need to reassess the benefits of this
      technique in tumours with lymphatic invasion.

PMID- 7713136
TI  - Mediastinal tumor and Klinefelter's syndrome.
AB  - Klinefelter's syndrome with karyotype 47,XXY in patients with primary
      extragonadal germ cell tumors rarely occurs. The endocrinology of Klinefelter's
      syndrome is changed; elevated beta-human choriomic gonadotropin levels are
      present. Chemotherapy and thoracic surgery brought complete remission in a
      patient with lung metastases.

PMID- 7713137
TI  - An unusual cause of urethral stricture: urethral lymphangioma.
AB  - We report an unusual case of urethral narrowing which is caused by lymphangioma.
      The natural history of lymphangioma of the urethra is described. To our
      knowledge, lymphangioma of the urethra as a cause of urethral stricture has not
      been reported to date. Although lymphangioma of the urethra is a benign disease,
      it must be included among the causes of urethral stricture.

PMID- 7713138
TI  - [3H]7-OH-DPAT is capable of labeling dopamine D2 as well as D3 receptors.
AB  - The binding of [3H](+)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin ([3H]7-OH-DPAT)
      to dopamine D2 and D3 receptors expressed in Chinese hamster ovary (CHO) cells
      was investigated and compared with [3H]methylspiperone. [3H]7-OH-DPAT labeled the
      D3 receptor in the CHO cells in a guanine nucleotide-insensitive fashion and
      exhibited a Kd of about 0.5 nM. In the presence of MgCl2. [3H]7-OH-DPAT was also
      found to label the D2 receptor in CHO cells with high affinity (3.6 nM). The
      binding of [3H]7-OH-DPAT to the D2 receptor was sensitive to guanine nucleotides
      suggesting occupancy of a high affinity G protein-coupled state of the receptor.
      These results suggest that caution should be exercised when using [3H]7-OH-DPAT
      to label the dopamine D3 receptor in brain tissues.

PMID- 7713139
TI  - Epithelium-derived inhibitory prostaglandins modulate human bronchial smooth
      muscle responses to histamine.
AB  - The role of the bronchial epithelium and inhibitory prostaglandins in the
      induction of histamine tachyphylaxis in human isolated bronchial smooth muscle
      was investigated using bronchi obtained from 14 patients who had been treated
      with non-steroidal anti-inflammatory drugs (NSAID) for > 2 months and from 14
      untreated patients. Epithelium-intact bronchial strips from untreated patients
      demonstrated tachyphylaxis to histamine with the maximum response (Emax) reduced
      by 30 +/- 5% (P < 0.02) and the EC50 increased 1.86-fold (P < 0.02).
      Tachyphylaxis was not observed in epithelium-denuded strips. In epithelium-intact
      bronchial preparations from NSAID treated patients, the mean initial maximum
      tension generated in response to histamine was significantly greater than that
      for bronchial preparations from untreated patients (P < 0.05). In NSAID-treated
      patients, both epithelium-intact and denuded preparations failed to demonstrate
      tachyphylaxis. The generation of prostaglandin E2 and prostacyclin was assessed
      by radio-immunoassay using bronchi from untreated patients (n = 8). In epithelium
      intact bronchial preparations, the generation of both prostaglandin E2 and
      prostacyclin was significantly increased by histamine exposure (P < 0.05) and was
      completely inhibited by indomethacin. However, the selective histamine H2
      receptor antagonist, ranitidine, selectively inhibited the synthesis of
      prostaglandin E2 alone. Production of both prostaglandins was not altered by
      exposure to acetylcholine. These results suggest that prostaglandin E2 and
      prostacyclin are released primarily from the epithelium in response to histamine
      and may be specifically involved in inhibiting human bronchial smooth muscle
      responsiveness to this mediator. Significantly, the release of prostaglandin E2
      appears to be selectively controlled by histamine H2 receptors, resident on the
      epithelium.

PMID- 7713140
TI  - Potentiation by alcuronium of the antimuscarinic effect of N-methylscopolamine in
      guinea pig left atria.
AB  - Alcuronium is known to stabilize allosterically the binding of the muscarinic
      antagonist N-methylscopolamine to muscarinic M2 receptors and thus to elevate the
      equilibrium binding of N-methylscopolamine in homogenized cardiac tissue. In
      order to check for a functional consequence of this effect, the action of
      alcuronium alone and in combination with N-methylscopolamine was determined in
      contracting guinea pig left auricles with oxotremorine-M as the negative
      inotropic agonist. For sake of comparison, the allosteric modulator W84 = hexane
      1,6-bis(dimethyl-3'- phthalimidopropyl-ammonium bromide) was included. Alcuronium
      displayed a weak antimuscarinic action (pA2 = 5.7). In conjunction with 10(-7) M
      N-methylscopolamine, alcuronium (> or = 10(-6) M) induced a more pronounced
      antimuscarinic effect than expected for a combination of competitive antagonists.
      The extent of overadditivity with combinations of W84 and 10(-7) M N
      methylscopolamine was smaller. In conclusion, alcuronium potentiates the
      antimuscarinic effect of N-methylscopolamine in contracting cardiac preparations
      with high effectivity.

PMID- 7713141
TI  - Rolipram, a cyclic AMP-selective phosphodiesterase inhibitor, reduces neuronal
      damage following cerebral ischemia in the gerbil.
AB  - We examined the effects of rolipram, a cyclic AMP-selective phosphodiesterase
      inhibitor, on cerebral ischemia-induced neuronal damage in Mongolian gerbils.
      Transient forebrain ischemia was induced by 3-min occlusion of bilateral common
      carotid arteries. Rolipram, at a dose of 0.3 or 3 mg/kg, was injected i.p. 30 min
      before ischemia. Histopathological observations showed that neuronal damage to
      the hippocampal CA1 subfield, which was seen 7 days after ischemia in vehicle
      treated animals, was reduced in animals treated with the higher dose of rolipram.

PMID- 7713142
TI  - Differential cross-tolerance between analgesia produced by alpha 2-adrenoceptor
      agonists and receptor subtype selective opioid treatments.
AB  - Analgesic cross-tolerance between alpha 2-adrenoceptor and opioid receptor
      agonists was studied using the mouse tail-flick assay. Mice tolerant to clonidine
      (0.3 mg/kg s.c.) or xylazine (7 mg/kg s.c.) were cross-tolerant to morphine (5
      mg/kg s.c.), nalorphine (70 mg/kg s.c.) and supraspinal [D
      Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO; 4 ng i.c.v.), but not trans-(+/-)-3,4
      dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl] benzeneacetamide
      methanesulfonate (U50,488; 5 mg/kg s.c.), spinal DAMGO (10 ng i.t.), supraspinal
      [D-Pen2,D-Pen5]enkephalin (DPDPE; 9 micrograms i.c.v.) or spinal DPDPE (700 ng
      i.t.). In the complimentary studies, mice tolerant to morphine and nalorphine
      were cross-tolerant to both of the alpha 2-adrenoceptor agonists, but U50,488
      tolerant mice were not. The results suggest differential interactions between
      alpha 2-adrenoceptor and mu 1-, mu 2-, delta-, kappa 1- and kappa 3-opioid
      analgesic circuitry.

PMID- 7713143
TI  - Comparison of responses to adrenomedullin and adrenomedullin analogs in the
      mesenteric vascular bed of the cat.
AB  - Responses to adrenomedullin, a newly discovered hypotensive peptide isolated from
      human pheochromocytoma cells, and the carboxy terminal 15-52 (adrenomedullin-(15
      52)) and 22-52 (adrenomedullin-(22-52)) amino acid fragments of adrenomedullin
      were investigated in the mesenteric vascular bed of the cat. Under constant flow
      conditions, injections of adrenomedullin, adrenomedullin-(15-52), and calcitonin
      gene-related peptide (CGRP) in doses of 0.003-1 nmol into the perfused superior
      mesenteric artery caused significant dose-related decreases in mesenteric
      arterial perfusion pressure. Mesenteric vasodilator responses to adrenomedullin
      and adrenomedullin-(15-52) were similar in magnitude and duration, while
      vasodilator responses to CGRP were greater in magnitude and longer in duration
      than those produced by adrenomedullin or adrenomedullin-(15-52) when these agents
      were injected in doses of 0.1-1 nmol. Adrenomedullin-(22-52) caused no
      significant change in mesenteric arterial perfusion pressure when injected in
      doses up to 10 nmol. These results suggest that amino acids 15-52 and the six
      membered ring structure of adrenomedullin are important for the expression of
      vasodilator activity in the mesenteric vascular bed of the cat.

PMID- 7713145
TI  - Prostaglandin E2, but not prostacyclin inhibits histamine-induced contraction of
      human bronchial smooth muscle.
AB  - The effects of exogenous prostaglandin E2 and prostacyclin on the function of
      epithelium-intact and epithelium-denuded human bronchial smooth muscle and the
      role of these mediators in the inhibition of histamine-induced contraction was
      examined using bronchi obtained from 22 patients undergoing thoracotomy. Under
      resting tension, a variable biphasic contraction-relaxation or monophasic
      relaxation was observed following the cumulative addition of exogenous
      prostaglandin E2 or prostacyclin. Cumulative addition of these mediators to pre
      contracted bronchi produced incomplete relaxation, irrespective of the presence
      of epithelium. Addition of prostaglandin E2, at a concentration equating to that
      produced after histamine stimulation (1.2 x 10(-9)M), produced a reduction (24%)
      in the maximum contractile response (Emax) to a subsequent histamine challenge (P
      < 0.03). However, a similar response was not observed after the addition of
      prostacyclin at a concentration similar to that produced endogenously (6.5 x 10(
      10)M). The combined addition of both mediators resulted in a significant
      reduction (26%) in the Emax to histamine (P < 0.02) but this effect was not
      statistically different to that of prostaglandin E2 alone. The addition of
      supramaximal concentrations (1 microM) of each prostanoid, either alone or in
      combination, did not inhibit responses to histamine. These data suggest that
      whilst prostaglandin E2 does not act as a direct acting relaxant agonist, it may
      inhibit histamine-induced muscle contraction and thereby contribute to the
      observed tachyphylaxis to this mediator. In contrast, prostacyclin appears to be
      of little importance in modulating human bronchial smooth muscle responses to
      histamine either directly or by enhancing responses to prostaglandin E2. The
      inhibitory effect of prostaglandin E2 appears to be concentration-dependent and
      suggests a bimodal action of this mediator in human airways.

PMID- 7713144
TI  - Influence of NMDA receptor ligands on thyrotropin-releasing hormone-induced
      scratching in rabbits.
AB  - The influence of intracaudate administration of N-methyl-D-aspartic acid (NMDA)
      and of the competitive NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric
      acid (AP-5) was studied on thyrotropin-releasing hormone (TRH)-induced scratching
      in rabbits. NMDA (28 nmol) significantly increased the latency of TRH-induced
      scratching but did not modify the duration of this behaviour. Conversely, AP-5
      (0.5 mumol) significantly potentiated scratching duration. Since TRH-induced
      scratching has been reported to be a dopamine-dependent behaviour, these results
      suggest that NMDA receptor ligands modulate dopaminergic neurotransmission.

PMID- 7713146
TI  - The role of alpha-adrenergic mechanisms within the area postrema in dopamine
      induced emesis.
AB  - Intracerebroventricular injection of dopamine (0.5-4.0 mg) produced dose
      dependent and short-lasting emesis (1-8 min) in cats, which was abolished after
      ablation of the area postrema. Relatively selective alpha 2-adrenoceptor
      antagonists (yohimbine and idazoxan) and a mixed alpha 1- and alpha 2
      adrenoceptor antagonist (tolazoline), but not a non-selective alpha 1
      adrenoceptor antagonist (prazosin), injected intracerebroventricularly inhibited
      the emesis induced by intracerebroventricular dopamine. However, dopamine
      receptor antagonists (chlorpromazine, droperidol, spiperone, domperidone,
      triflupromazine, sulpiride and metoclopramide), an antimuscarinic drug
      (atropine), a ganglionic blocking agent (mecamylamine), an opioid receptor
      antagonist (naloxone) and a 5-HT receptor antagonist (methysergide), all injected
      intracerebroventricularly, had no significant effect on emesis evoked by
      intracerebroventricular dopamine. The emetic response to intracerebroventricular
      dopamine was attenuated in cats pretreated with intracerebroventricular
      reserpine, 6-hydroxydopamine, alpha-methyl-p-tyrosine and hemicholinium-3. It is
      postulated that dopamine-induced emesis is mediated through the release of
      noradrenaline acting at alpha 2-adrenoceptors and that it depends on the
      integrity of monoaminergic and possibly cholinergic structures within the area
      postrema. It appears, therefore, that the emetic effect of
      intracerebroventricular dopamine is mediated by adrenergic rather than
      dopaminergic mechanisms in the area postrema, at least in the cat.

PMID- 7713147
TI  - Comparison of antiplatelet effects of FK409, a spontaneous nitric oxide releaser,
      with those of TRK-100, a prostacyclin analogue.
AB  - The anti-platelet effects of FK409 ((+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro
      3-hexeneamide) , a new spontaneous nitric oxide releaser, and TRK-100 (sodium dl
      4-[(1R,2R,3aS,8bS)-1,2,3a,8b-tetra-hydro-2-hydroxy-1-[(3S ,4RS)-3-hydroxy- 4
      methyl-oct-6-yen-(E)-1-enyl]-5-cyclopenta[b]benzofuranyl]butyrate), a stable
      prostacyclin analogue, were studied both in vivo and in vitro. FK409 and TRK-100
      inhibited ADP-induced platelet aggregation in rat platelet-rich plasma at 1.0 and
      0.032 microM, respectively. In a rat extracorporeal shunt model, FK409 suppressed
      thrombus formation dose dependently and significantly at 1.0 mg/kg and showed the
      maximum inhibition (52% inhibition) at 10 mg/kg. TRK-100 showed 79% inhibition of
      thrombus formation at 1.0 mg/kg, but not at less than 1.0 mg/kg. At the doses
      required for antiplatelet effects, TRK-100 decreased mean blood pressure
      significantly but FK409 did not alter the blood pressure. These data suggest that
      FK409 shows more selective activities on platelets than TRK-100 in these
      experiments.

PMID- 7713148
TI  - Socially defeated male rats display a blunted adrenocortical response to a low
      dose of 8-OH-DPAT.
AB  - The study examined in male Wistar rats the influence of social defeat on the
      neuroendocrine stress response system using injection of the 5-HT1A receptor
      agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), as the
      pharmacological challenge. Social defeat was defined by the submissive postures
      displayed by the Wistar rats which were threatened and attacked by Tryon Maze
      Dull S3 rats for 10 min. 18-20 h after social defeat, the defeated rats were
      injected intravenously (i.v.) with a low and high dose of 8-OH-DPAT in their home
      cages. Blood samples were withdrawn from the freely moving cannulated rats for
      determination of plasma corticosterone and catecholamines. The corticosterone
      response to the low dose of 8-OH-DPAT (0.05 mg/kg, i.v.) was significantly
      diminished in the defeated rats as compared to the controls, but this dose failed
      to affect catecholamine concentrations. The high dose of 8-OH-DPAT (0.15 mg/kg,
      i.v.) significantly elevated corticosterone and adrenaline levels in defeated and
      control rats to the same extent, whereas no effect on noradrenaline was found.
      The present data thus indicate that social defeat blunts 5-HT1A receptor-mediated
      adrenocortical activation probably via a decrease in the sensitivity of a
      population of postsynaptic 5-HT receptors.

PMID- 7713149
TI  - Opioid effects on spinal [3H]5-hydroxytryptamine release are not related to their
      antinociceptive action.
AB  - Several opioid compounds were evaluated for an ability to modulate the K(+)
      stimulated release of [3H]serotonin ([3H]5-hydroxytryptamine, [3H]5-HT) from rat
      spinal cord synaptosomal and tissue slice preparations. Selective kappa-opioid
      receptor agonists depressed K(+)-stimulated release of the radiolabelled
      transmitter from both tissue preparations, an effect which was reversed by
      norbinaltorphimine. Conversely, the selective mu- and delta-opioid receptor
      agonists [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO) and [D-Pen2,D-Pen5]enkephalin
      (DPDPE), respectively, enhanced the K(+)-stimulated release of [3H]5-HT. This
      effect was only seen using the tissue slice preparation. When used at
      concentrations near its reported Kd for mu-opioid receptors, the selective mu
      opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) blocked
      the action of DAMGO, but had no effect on the action of DPDPE. However, higher
      concentrations of CTOP, as well as all effective concentrations of selective
      delta-opioid receptor antagonists, blocked the action of both DAMGO and DPDPE.
      All agonist effects on spinal 5-HT release, regardless of the tissue preparation,
      were only seen at high (microM) concentrations. Moreover, effects of the opioid
      agonists were not consistent with the reported involvement of spinal 5-HT
      neurotransmission in the mediation of their antinociceptive action. Thus, the
      ability of opioids to modulate spinal 5-HT release appears to be of minimal
      physiological significance.

PMID- 7713150
TI  - Mechanism of interaction between neuropeptide Y and angiotensin II in the rabbit
      femoral artery.
AB  - Neuropeptide Y has direct vasoconstrictor actions and potentiates the effects of
      other vasoconstrictor agents. To find out whether both effects of neuropeptide Y
      are mediated via the same receptor and intracellular mechanism, the interaction
      between neuropeptide Y and angiotensin II was studied in rabbit femoral arteries.
      In this preparation, neuropeptide Y, but not its 13-36 fragment, induced
      constriction. Only neuropeptide Y potentiated the vasoconstrictor response to
      angiotensin II and the associated rise in inositol-1-phosphate. These
      potentiating effects of neuropeptide Y were totally prevented by removal of
      extracellular Ca2+, partially prevented by a Ca(2+)-channel blocker and mimicked
      by a Ca(2+)-channel activator. Pharmacological modulation of adenylate cyclase
      had no effect. These results suggest that the direct and indirect vascular
      effects of neuropeptide Y are mediated via Y1 receptors and depend on the influx
      of extracellular Ca2+. The rise in inositol-1-phosphate seems to be secondary to
      an increase in intracellular Ca2+, while modulation of adenylate cyclase is
      apparently not involved.

PMID- 7713151
TI  - A preliminary investigation of the mechanisms underlying cannabinoid tolerance in
      the mouse vas deferens.
AB  - Vasa deferentia taken from mice treated with delta 9-tetrahydrocannabinol (20
      mg/kg i.p., once daily for 2 days) showed tolerance to the inhibitory effect of
      the cannabinoid, R-(+)-arachidonyl-1'-hydroxy-2'-propylamide, on electrically
      evoked twitches. This treatment did not induce tolerance to the inhibitory
      effects on the twitch response of morphine or clonidine or of selective mu-,
      delta- or kappa-opioid receptor agonists. Nor did it affect the contractile
      potencies of noradrenaline or beta,gamma-methylene-L-ATP. We suggest that
      cannabinoid tolerance in the vas deferens is attributable neither to
      downregulation of opioid receptors or alpha 2-adrenoceptors nor to an increased
      sensitivity of this tissue to its main contractile transmitters noradrenaline and
      ATP. A concentration of delta 9-tetrahydrocannabinol that inhibits electrically
      evoked twitches of the vas deferens (100 nM) did not alter the ability of
      noradrenaline or beta,gamma-methylene-L-ATP to induce contractions suggesting
      that delta 9-tetrahydrocannabinol inhibits the twitch response by acting
      prejunctionally.

PMID- 7713152
TI  - Effect of phenylmethylsulphonyl fluoride on the potency of anandamide as an
      inhibitor of electrically evoked contractions in two isolated tissue
      preparations.
AB  - The endogenous cannabinoid receptor ligand, anandamide, produced a concentration
      related inhibition of electrically evoked contractions of the guinea-pig
      myenteric plexus preparation. Its potency was markedly enhanced by
      phenylmethylsulphonyl fluoride (2.0-200 microM) which presumably acts by
      inhibiting the hydrolysis of anandamide in this preparation. The degree of this
      potentiation increased with the concentration of phenylmethylsulphonyl fluoride
      used. The methyl analogue of anandamide, R-(+)-arachidonyl-1'-hydroxy-2'
      propylamide, also inhibited contractions of the guinea-pig myenteric plexus
      preparation. The potency of this compound was much less affected by
      phenylmethylsulphonyl fluoride than was the potency of anandamide, confirming its
      greater resistance to hydrolysis. Phenylmethylsulphonyl fluoride did not alter
      the inhibitory potency of the cannabinoid, CP 55,940 ((-)-3-[2-hydroxy-4-(1,1
      dimethylheptyl)phenyl]-4- [3-hydroxypropyl]cyclohexan-1-ol), which is not an
      amidase substrate. Nor did phenylmethylsulphonyl fluoride affect the ability of
      anandamide to inhibit electrically evoked contractions of the mouse vas deferens,
      suggesting that anandamide does not undergo hydrolysis in this tissue.

PMID- 7713153
TI  - Effects of GBR 12909 on locomotor activity and dopamine turnover in mice:
      comparison with apomorphine.
AB  - The effects of GBR 12909 1-[2-[bis(4-fluorophenyl)methoxy]-ethyl]-4- [3
      phenylpropyl]piperazine, a very potent and selective dopamine uptake inhibitor,
      and apomorphine, a dopamine receptor agonist, alone and in combination were
      investigated on locomotor activity and dopamine turnover in discrete brain
      regions of mice. The levels of dopamine and its metabolites were examined 40 min
      after the administration of GBR 12909 and/or apomorphine, when the effects of the
      drugs on locomotor activity were approximately at a peak. GBR 12909 (10 mg/kg
      i.p.) reversed a low dose of apomorphine (0.05 mg/kg s.c.)-induced suppression in
      locomotor activity and significantly increased this activity. Despite the
      dramatic change in the behavior, GBR 12909 did not influence the decrease in 3,4
      dihydroxyphenylacetic acid (DOPAC)/dopamine ratio (which is one of the
      indications of transmitter turnover) induced by a low dose of apomorphine in the
      nucleus accumbens and striatum. In contrast, GBR 12909 did not enhance the high
      dose apomorphine (2 mg/kg s.c.)-induced hyperlocomotion, and did not modify the
      larger decrease in dopamine turnover produced by the high dose of apomorphine in
      the frontal cortex, nucleus accumbens and striatum. This suggests that
      postsynaptic dopamine receptors may reach maximum stimulation at a high dose of
      apomorphine. These results indicate that a behavioral change induced via
      stimulation of postsynaptic dopamine receptors does not necessarily lead to an
      alteration in dopamine turnover.

PMID- 7713154
TI  - BMY 7378 is a selective antagonist of the D subtype of alpha 1-adrenoceptors.
AB  - BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8- azaspiro[4.5]decane
      7,9-dione dihydrochloride), a 5-HT1A receptor partial agonist, also binds to
      alpha 1-adrenoceptors. Competition assays were performed using (+/-)-beta
      ([125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone ([125I]HEAT), and
      membranes prepared from Rat-1 fibroblasts expressing hamster alpha 1b-, bovine
      alpha 1c-, or rat alpha 1d-adrenoceptor, or their respective human homologues.
      Results indicate that BMY 7378 is selective for the alpha 1D-adrenoceptor subtype
      (pKi: hamster alpha 1b-adrenoceptor 6.2 +/- 0.03, human alpha 1b-adrenoceptor 7.2
      +/- 0.05; bovine alpha 1c-adrenoceptor 6.1 +/- 0.02, human alpha 1c-adrenoceptor
      6.6 +/- 0.20; rat alpha 1d-adrenoceptor 8.2 +/- 0.06, human alpha 1d-adrenoceptor
      9.4 +/- 0.05) and has high affinity (pA2, 8.9 +/- 0.1) for rat aorta alpha 1
      adrenoceptor.

PMID- 7713155
TI  - Systemic administration of the NMDA receptor antagonist MK-801 potentiates
      circling induced by intrastriatal microinjection of dopamine.
AB  - Systemic administration of the non-competitive antagonist of NMDA receptors MK
      801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine)
      potentiates the circling response induced by direct stimulation of the striatal
      dopaminergic receptors through intracerebral application of dopamine.
      Microinjection of dopamine (1, 5, 25 or 50 micrograms/1.0 microliters) induced a
      dose-dependent contralateral circling response, when injected directly into the
      lesioned side of unilaterally 6-hydroxydopamine-lesioned rats. Interestingly,
      intrastriatal application of dopamine (1, 5, 25 or 50 micrograms/1.0 microliters)
      followed by a systemic administration of MK-801 (100 micrograms/kg i.p.) produced
      a potentiated contralateral circling response in unilaterally 6-hydroxydopamine
      (6-OHDA)-lesioned rats. This motor effect is reversed compared to the marked
      ipsilateral circling response produced by MK-801 when given alone. Moreover, the
      potentiated responses persist 4-fold longer compared to the circling induced by
      dopamine alone. The results suggest that the potentiation by NMDA receptor
      antagonists of motor activity induced by dopaminergic agonists in animal models
      of Parkinson's disease cannot be ascribed simply to increased release of
      dopamine. Other mechanisms including increased sensitivity of dopamine D1
      receptors or blockade or glutamatergic transmission in output structures must be
      considered.

PMID- 7713157
TI  - Characterization of the alpha 1-adrenoceptors of dog liver: predominance of the
      alpha 1A-subtype.
AB  - Using dog liver membranes we observed that [125I]HEAT ((+/-)-beta-([125I]iodo-4
      hydroxyphenyl)-ethyl-aminomethyl-tetralone) binds with high affinity (KD 97 pM)
      to a discrete number of sites (Bmax 40 fmol/mg protein) with the pharmacological
      characteristics expected for alpha 1-adrenoceptors. Such sites were inactivated
      by pretreatment with chloroethylclonidine. Binding competition experiments
      indicated the following order of potency: (a) for agonists: oxymetazoline >
      epinephrine > or = norepinephrine > methoxamine and (b) for antagonists: WB4101 >
      or = 5-methyl-urapidil = prazosin > or = benoxathian > or = (+)-niguldipine >
      phentolamine. Northern analysis indicated that total RNA isolated from dog liver
      hybridized with an alpha 1c selective probe (bovine brain). The orders of potency
      for agonists and antagonists, their Ki values and the Northern analysis suggest
      that dog liver expresses alpha 1A-adrenoceptors.

PMID- 7713156
TI  - Changes in prepulse inhibition after local administration of NMDA receptor
      ligands in the core region of the rat nucleus accumbens.
AB  - The dopamine and glutamate hypotheses are two pharmacological models for
      schizophrenia. In the present investigations, the prepulse inhibition paradigm
      was used to evaluate the role of the nucleus accumbens core region in both
      models. Prepulse inhibition is known to be decreased in schizophrenics, when
      compared with control patients, and in rats after systemic injection of dopamine
      receptor agonists and non-competitive antagonists of the NMDA receptor. In the
      present study injection of dopamine in the rat nucleus accumbens core region also
      decreased prepulse inhibition. Injections of NMDA decreased, whereas a low dose
      of the competitive NMDA receptor antagonist (+/-)-2-amino-5-phosphonopentanoic
      acid (AP-5) and the non-competitive NMDA receptor antagonist (5R,10S)-(+)-5
      methyl-10,11-dihydroxy-5H-dibenzo[a,d]cyclohepten-5 ,10-imine hydrogen maleate
      (MK-801) increased prepulse inhibition. The results indicate an involvement of
      the accumbens core in mediating the systemic effects on prepulse inhibition of
      dopamine receptor agonists but not of non-competitive NMDA receptor antagonists.

PMID- 7713158
TI  - Diurnal alteration in opiate effects on the hypothalamo-pituitary-adrenal axis:
      changes in the mechanism of action.
AB  - Opioid control of the hypothalamo-pituitary-adrenocortical axis has a
      characteristic circadian rhythm (Kiem, Kanyicska, Stark and Fekete, 1987). To
      elucidate the mechanisms leading to circadian alterations of opioid control of
      the hypothalamo-pituitary-adrenocortical axis, and to look for the receptor type
      at which the p.m. inhibitory action of opioids occurs, we examined the effect of
      morphine at different doses and the interaction between naloxone and morphine at
      different times of day in intact male Wistar rats. In the morning: morphine (10
      and 30 mg/kg s.c.) significantly increased corticosterone secretion, while 3
      mg/kg s.c. had no effect. Naloxone in a dose of 2.5 mg/kg i.p. significantly
      antagonized the corticosterone-releasing effect of morphine, suggesting that the
      secretion of corticosterone induced by morphine is mediated via mu-opioid
      receptors. In the afternoon: basal plasma corticosterone levels were higher than
      those in the morning, and morphine caused a significant corticosterone increase
      only at the dose of 30 mg/kg, and had no effect in the dose of 10 mg/kg. Morphine
      significantly decreased corticosterone levels in the dose of 3 mg/kg. This
      inhibitory action lasted approximately 3 h after morphine injection and was able
      to inhibit the circadian evening rise of corticosterone. The effect of morphine
      and the interaction between naloxone and morphine on prolactin secretion remained
      unchanged from a.m. to p.m.; naloxone (2.5 mg/kg i.p.) which inhibited the 30
      mg/kg morphine-induced corticosterone rise in the morning failed to antagonize
      the 3 mg/kg morphine-induced decrease of corticosterone secretion in the
      afternoon. A high dose of naloxone (10 mg/kg i.p.) effectively prevented the 3
      mg/kg morphine-induced p.m. inhibition of corticosterone secretion.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7713159
TI  - Mexiletine and lidocaine reduce post-ischemic functional and biochemical
      dysfunction of perfused hearts.
AB  - The present study was undertaken to determine whether class Ib antiarrhythmic
      agents, mexiletine and lidocaine, exert beneficial effects on
      ischemia/reperfusion-induced cardiac contractile dysfunction. Isolated rat hearts
      were subjected to 35-min global ischemia, followed by 60-min reperfusion and the
      functional and metabolic alterations were examined with and without mexiletine or
      lidocaine treatment. Ischemia/reperfusion resulted in a lack of recovery of
      contractile function, a sustained rise in left ventricular end-diastolic pressure
      and increased coronary perfusion pressure of the perfused heart during
      reperfusion. Contractile dysfunction was associated with increases in tissue Na+
      and Ca2+ levels, decreases in K+ and Mg2+ levels, and release of creatine kinase
      and purine nucleosides and bases (ATP metabolites) from the heart. Treatment of
      the perfused heart with either 10-100 microM of either mexiletine or lidocaine
      during pre-ischemia resulted in an enhancement of post-ischemic contractile
      recovery, a suppression of changes in tissue Na+, K+, Ca2+ and Mg2+ contents and
      an attenuation of the release of creatine kinase and ATP metabolites in an almost
      concentration-dependent manner. Tissue sodium accumulation was observed at the
      end of ischemia, which was also attenuated by pretreatment with these agents. The
      prevention of Na+ overload and accompanying Ca2+ overload in cardiac cells may be
      the mechanism underlying the improvement of post-ischemic contractile function of
      perfused hearts by these agents.

PMID- 7713160
TI  - Myocardial and pulmonary uptake of S-1'-[18F]fluorocarazolol in intact rats
      reflects radioligand binding to beta-adrenoceptors.
AB  - The biodistribution of S-(-)-4-(2-hydroxy-3-(1'-[18F]fluoroisopropyl)-
      aminopropoxy)carbazole ([18F]S-fluorocarazolol, a non-selective beta-adrenoceptor
      antagonist) was studied in rats (60 min after 18F injection when specific binding
      in peripheral organs was maximal). 18F uptake in brain, erythrocytes, heart and
      lung appeared to be linked to beta-adrenoceptors. CGP-20712A and ICI-89,406
      inhibited 18F uptake in heart (predominantly beta 1-adrenoceptors) more potently
      than in lungs (predominantly beta 2-adrenoceptors). In contrast, ICI-118,551 and
      procaterol were more potent in the lungs than in the heart. ICI-118,551 inhibited
      18F uptake in cerebellum (predominantly beta 2-adrenoceptors) more potently than
      in cerebral cortex (predominantly beta 1-adrenoceptors). Stereoselectivity of the
      in vivo binding was demonstrated since S-(-)-propranolol inhibited uptake in
      target tissues more effectively than R-(+)-propranolol. Myocardial and cerebral
      imaging may be hampered by poor heart-to-lung contrast and low signal-to-noise
      ratios, but [18F]S-fluorocarazolol seems suitable for positron emission
      tomography (PET) of pulmonary beta-adrenoceptors.

PMID- 7713161
TI  - The corticosterone-enhancing effects of the 5-HT1A receptor antagonist, (S)
      UH301, are not mediated by the 5-HT1A receptor.
AB  - We tried to antagonize the endocrine and behavioural changes induced by the
      selective 5-HT1A receptor agonist, flesinoxan, with the putative 5-HT1A receptor
      antagonist, (S)-UH301 ((S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin). The
      interaction of (S)-UH301 (3 and 10 mg/kg s.c.) with flesinoxan (3 mg/kg s.c.)
      showed no antagonistic effects of (S)-UH301 on flesinoxan-induced corticosterone
      secretion. In fact, like flesinoxan (1 and 3 mg/kg s.c.), (S)-UH301 (3 and 10
      mg/kg s.c.) itself dose dependently increased plasma corticosterone levels.
      Unlike flesinoxan, (S)-UH301 did not induce hyperglycemia, lower lip retraction
      and flat body posture. Moreover, flesinoxan-induced hyperglycemia and behavioural
      changes were effectively antagonized by (S)-UH301, showing potent 5-HT1A receptor
      antagonistic effects of (S)-UH301. Therefore we conclude that (S)-UH301 is a
      potent 5-HT1A receptor antagonist and that the (S)-UH301-induced corticosterone
      secretion is mediated by a non-5-HT1A receptor mechanism.

PMID- 7713162
TI  - Anti-inflammatory effects of a short-acting and a long-acting beta 2-adrenoceptor
      agonist in guinea pig skin.
AB  - The pharmacological modulation of the accumulation and function of eosinophils in
      tissues may have a significant impact in the treatment of allergic diseases such
      as asthma, atopic dermatitis and rhinitis. In this study, we have investigated
      the acute anti-inflammatory effects of a short-acting (salbutamol) and a long
      acting (salmeterol) beta 2-adrenoceptor agonist on 111In-accumulation and oedema
      formation in allergic and mediator-induced inflammation in guinea pig skin. Both
      salbutamol and salmeterol inhibited 111In-eosinophil accumulation induced by
      platelet-activating factor and in a passive cutaneous anaphylactic reaction when
      co-injected with the inflammatory stimuli or when given as a 30 min pretreatment.
      The inhibition was reversed by DL-propranolol, but not D-propranolol. Systemic
      treatment with salbutamol inhibited 111In-eosinophil accumulation and oedema
      formation when given as a 15 min, but not as a 3 h, pretreatment. In contrast,
      salmeterol was effective when given at both times. We conclude that a long
      duration of action of beta 2-adrenoceptor agonists is not necessary to
      demonstrate acute anti-inflammatory effects on eosinophil accumulation in guinea
      pig skin.

PMID- 7713163
TI  - Ebselen, a seleno-organic compound, protects against ethanol-induced murine
      gastric mucosal injury in both in vivo and in vitro systems.
AB  - The inhibitory effect of the seleno-organic compound ebselen on ethanol-induced
      murine gastric mucosal injury was examined. In an in vivo study, absolute ethanol
      (50 microliters/mouse, oral) produced marked gastric mucosal necrosis along with
      hemorrhage or edema and elevations in both lipid peroxide and peptidoleukotriene
      levels in the fundic mucosa. Pretreatment with ebselen (30 and 100 mg/kg, oral)
      significantly prevented this gastric mucosal injury and, further, remarkably
      decreased the elevated lipid peroxide and peptidoleukotriene levels. In an in
      vitro study using a murine gastric surface mucous cell line GSM06, exposure to
      ethanol concentration dependently elicited cell damage (7.5-17.5% ethanol) and an
      increase in lipid peroxides without alterations in peptidoleukotrienes (15%
      ethanol). Addition of ebselen (10 and 100 microM) to this system (15% ethanol)
      significantly inhibited the cell damage and completely prevented the increase in
      lipid peroxide level. These results indicate that ebselen protects against murine
      gastric mucosal injury both in vivo and in vitro, and that this protection may be
      related at least in part to its inhibitory action on lipid peroxides.

PMID- 7713164
TI  - Putative cognition enhancers reverse kynurenic acid antagonism at hippocampal
      NMDA receptors.
AB  - Oxiracetam, aniracetam and D-cycloserine, three putative cognition enhancers,
      were examined in a functional assay for NMDA receptors. Rat hippocampal slices or
      synaptosomes were labeled with [3H]noradrenaline and exposed to NMDA or glutamate
      in superfusion. NMDA (100 microM) elicited a remarkable rise (about 500%) in the
      release of [3H]noradrenaline from slices. The effect of NMDA was antagonized by
      the glutamate receptor blocker, kynurenic acid. The antagonism by 100 microM
      kynurenate was reduced by submicromolar concentrations of oxiracetam and totally
      reversed by 1 microM of the drug. The concentration-antagonism curve for
      kynurenic acid was shifted to the right in the presence of 0.2 or 1 microM
      oxiracetam. Aniracetam and D-cycloserine, as well as glycine and D-serine,
      behaved similarly to oxiracetam: all compounds, tested at 1 microM, reversed the
      antagonism by 100 microM kynurenate of the NMDA-evoked [3H]noradrenaline release.
      In superfused hippocampal synaptosomes, 100 microM NMDA or glutamic acid elicited
      the release of [3H]noradrenaline; the evoked release was enhanced by glycine, but
      not by oxiracetam. In this preparation 1 microM glycine or 1 microM oxiracetam
      prevented the antagonism by kynurenate of the NMDA- or the glutamate-evoked
      [3H]noradrenaline release. As kynurenic acid is an endogenous glutamate receptor
      antagonist whose brain levels are known to increase in conditions associated to
      cognitive deficits, it is proposed that the putative cognition enhancers tested
      may act in vivo by relieving the antagonism produced by excessive endogenous
      kynurenate.

PMID- 7713165
TI  - Do NMDA receptor-mediated changes in motor behaviour involve nitric oxide?
AB  - Nitric oxide (NO) synthase inhibitors were investigated for their effects on
      motor behaviour. In normal mice, NG-nitro-L-arginine (5-125 mg/kg i.p.) and 7
      nitroindazole (10-50 mg/kg i.p.), but not aminoguanidine (60-150 mg/kg i.p.)
      suppressed species-typical behaviours. In 24 h reserpine-treated mice, akinesia
      was reversed with the dopamine D1 receptor agonist 2,3,4,5-tetrahydro-7,8
      dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 3-30 mg/kg i.p.)
      and by the dopamine D2 receptor agonist N-n-propyl-N-phenylethyl-p-(3
      hydroxyethyl) ethylamine hydrochloride (RU 24213, 0.5-5 mg/kg s.c.), but not by
      any of the NO synthase inhibitors. NG-Nitro-L-arginine and 7-nitroindazole (not
      aminoguanidine) suppressed D1 and D2 receptor agonist-induced locomotion, but L
      arginine (500 mg/kg i.p.) was not always able to prevent this effect. These
      results suggest that continued activity of constitutive NO synthase is necessary
      for normal body movements to occur. The difference in the interaction profiles of
      constitutive NO synthase inhibitors and NMDA antagonists with dopaminergic drugs,
      indicates that inhibition of NO generation is not a factor in the well-known D1
      facilitatory effect of glutamate receptor blockade.

PMID- 7713166
TI  - Intrathecal alpha-trinositol facilitates the flexor reflex but does not block the
      depressive effect of neuropeptide Y.
AB  - We have studied the effects of alpha-trinositol (D-myo-inositol-1,2,6
      trisphosphate, PP56), a putative antagonist of neuropeptide Y receptors, on the
      nociceptive flexor reflex in decerebrate, spinalized rats after intrathecal and
      intravenous administration. Intrathecal alpha-trinositol caused strong and
      prolonged facilitation of the flexor reflex, which was usually associated with an
      increase in spontaneous motoneuron activity. The reflex depressive effect of
      intrathecal neuropeptide Y was neither blocked nor reversed by alpha-trinositol.
      Intravenous alpha-trinositol at low doses had no effect on the flexor reflex and
      at high dose, reflex facilitation was sometimes observed. It is concluded that
      alpha-trinositol acts as a spinal excitant and is not an antagonist of the
      neuropeptide Y receptor in the rat spinal cord.

PMID- 7713167
TI  - Blockers for excitatory effects of achatin-I, a tetrapeptide having a D
      phenylalanine residue, on a snail neurone.
AB  - Some histamine H1 receptor antagonists suppressed the inward current (Iin) of an
      Achatina identifiable neurone type, PON (periodically oscillating neurone),
      caused by an Achatina endogenous tetrapeptide having a D-phenylalanine residue,
      achatin-I (Gly-D-Phe-Ala-Asp), under voltage clamp. Achatin-I was applied locally
      to the neurone by brief pneumatic pressure ejection and antagonists were
      administered by perfusion. The dose-response curves of the effective histamine H1
      antagonists indicated their potency order to suppress the Iin as follows:
      chlorcyclizine, promethazine, triprolidine and homochlorcyclizine > trimeprazine
      and clemastine > diphenylpyraline. The potent drugs were mostly piperazine and
      phenothiazine types. The effects of chlorcyclizine, promethazine and triprolidine
      on the dose (the duration of the pressure ejection)-response curve of achatin-I
      indicated that these drugs affected the Iin caused by achatin-I in a non
      competitive manner. The antagonists for the receptors of the small-molecule
      neurotransmitters other than histamine H1, such as histamine H2, acetylcholine,
      gamma-aminobutyric acid (GABA), L-glutamic acid, dopamine, alpha- and beta
      adrenalin and 5-hydroxytryptamine, had no effect on the Iin caused by achatin-I.

PMID- 7713168
TI  - GR159897, a potent non-peptide antagonist at tachykinin NK2 receptors.
AB  - GR159897 ((R)-1-[2-(5-fluoro-1H-indol-3-yl)ethyl]-4-methoxy-4-
      [(phenylsulfinyl)methyl]piperidine) is a novel, highly potent and selective non
      peptide antagonist at tachykinin NK2 receptors. GR159897 inhibited binding of the
      NK2 receptor antagonist radioligand [3H]cyclohexylcarbonyl-Gly-Ala-(D)Trp-Phe
      NMe2 ([3H]GR100679) to human ileum NK2 receptors transfected into Chinese hamster
      ovary cells (pKi 9.5) and to rat colon membranes (pKi 10.0). GR159897 was a
      competitive antagonist of contractions induced by the NK2 receptor agonist
      [Lys3,Gly8-R-gamma-lactam-Leu9]neurokinin A-(3-10) (GR64349) in guinea-pig
      trachea (pA2 8.7), and had negligible activity at human NK1 receptors transfected
      into Chinese hamster ovary cells (pKi 5.3), NK1 receptors in guinea-pig trachea
      (pKB < 5) or NK3 receptors in guinea-pig cerebral cortex (pKi < 5). In vivo, in
      the anaesthetised guinea-pig, GR159897 (0.12 mg.kg-1 i.v.) potently antagonised
      bronchoconstriction induced by GR64349 (dose-ratio = 28), with a long duration of
      action (3 h). GR159897 should be a useful tool for studying the physiological and
      pathophysiological role of tachykinin NK2 receptor activation.

PMID- 7713169
TI  - Carrageenin-evoked c-Fos expression in rat lumbar spinal cord: the effects of
      indomethacin.
AB  - This study evaluated the effects of systemic indomethacin on carrageenin evoked c
      Fos expression in rat lumbar spinal cord neurons. Fos-like immunoreactivity was
      not observed after the intraplantar injection of the control vehicle saline. 2 h
      after administration of carrageenin (6 mg/150 microliters) into the hind limb,
      Fos-like immunoreactive neurons were observed in the lumbar spinal cord (64
      labelled neurons per L4-L5 sections) and were numerous in the superficial laminae
      (I-II), whereas at 3-4 h both superficial and deeper laminae (V, VI and ventral
      horn) were labelled. 3 h after carrageenin administration, maximal Fos-like
      immunoreactivity was observed (104 labelled neurons per L4-L5 sections). At later
      time points Fos-like immunoreactivity was observed predominantly in the deeper
      laminae. Fos-like immunoreactivity was rarely observed within laminae III-IV at
      any of the time points. At 24 h, the number of Fos-like immunoreactive neurons
      decreased (36 labelled neurons per L4-L5 sections). With increasing doses of
      carrageenin, an increase in the number of Fos-like immunoreactive neurons was
      observed. The number of Fos-like immunoreactive neurons induced by the
      carrageenin stimulation (6 mg, at 3 h) was clearly reduced by oral pretreatment
      with indomethacin (20 mg/kg). In addition, i.v. indomethacin (1, 2.5 or 5 mg/kg)
      dose dependently reduced the number of Fos-like immunoreactive neurons and the
      inflammation of the paw and the ankle of the injected foot. A strong relationship
      between the effect of indomethacin on c-Fos expression and its effect on
      inflammatory processes was observed. These results suggest that Fos-like
      immunoreactivity induced by carrageenin inflammation may be a very useful tool to
      study the effects of anti-inflammatory drugs, at both peripheral and central
      levels of inflammation.

PMID- 7713170
TI  - Neonatal damage to neocortex abolishes the anxiolytic action of diazepam in adult
      rats.
AB  - A neonatal cerebral cortical lesion was made in rats and the effects of diazepam
      on ultrasonic isolation calls in pups and footshock-elicited ultrasonic distress
      calls in young adult rats were assessed. There was no indication that the
      cortical lesion influenced the production of the ultrasonic distress calls in
      either pups or adults. Diazepam attenuated the ultrasonic isolation calls in all
      the pups with and without cortical lesion, and the distress calls in normal adult
      rats. However, diazepam failed to exert the effect in rats which received a
      neonatal cortical lesion. 8-Hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8
      OH-DPAT), another anxiolytic, was effective to diminish the distress calls even
      in the adult rats which had had the neonatal damage to the cortex. These findings
      indicate that the intact cerebral cortex is not always required for production of
      ultrasonic distress calls; however, the development of the neuronal mechanism
      involving benzodiazepine receptors to inhibit the ultrasonic expression of
      anxiety or fear in adult rats is dependent on the integrity of the cerebral
      cortex.

PMID- 7713171
TI  - In vitro effects of capsaicin: antiarrhythmic and antiischemic activity.
AB  - The antiarrhythmic effects of vehicle (0.1% dimethyl sulfoxide: DMSO) or
      capsaicin were evaluated in isolated perfused rat and guinea pig heart
      preparations. In the rat, capsaicin reduced ischemic ventricular tachycardia from
      100% in control to 0%, and ischemic ventricular fibrillation from 60% in control
      to 0% at 30 microM, and diltiazem reduced the incidence of ischemic ventricular
      tachycardia and ventricular fibrillation to 55% and 0%, respectively. Reperfusion
      ventricular fibrillation was reduced from 90% to 20% and 33% for capsaicin and
      diltiazem, respectively, at these concentrations. In isolated perfused globally
      ischemic rat hearts, antiischemic efficacy was assessed as a significant
      extension (36% and 50%) in time to contracture with 30 microM capsaicin and 1
      microM diltiazem, respectively. Capsaicin reduced left ventricular developed
      pressure by 35% in non-ischemic rat hearts, and increased coronary flow by 40%.
      The increased time to contracture for either compound was not blocked by
      glyburide (0.1 microM) suggesting a lack of any involvement of ATP-sensitive K+
      channels. In isolated guinea pig hearts subjected to global ischemia, capsaicin
      and diltiazem reduced reperfusion ventricular fibrillation from 100% to 10% and
      0% at 30 and 3 microM, respectively. Electrophysiologic evaluation in guinea pig
      papillary muscles using standard microelectrode techniques demonstrated
      significant (P < 0.05) action potential durations at 90% repolarization
      shortening at 1 Hz by 9%, 28% and 39%, and 23%, 37% and 51% at 10, 30, and 100
      microM of capsaicin or diltiazem, respectively. Unlike diltiazem, no changes in
      action potential duration were observed with capsaicin (up to 100 microM) at
      faster stimulation rates (5 Hz). In conclusion, capsaicin displays both
      antiarrhythmic and antiischemic efficacy. These data suggest that the effects of
      capsaicin are mediated primarily through block of Ca2+ channels in these
      preparations.

PMID- 7713173
TI  - A new aspect of the antiproliferative action of peripheral-type benzodiazepine
      receptor ligands.
AB  - Ro 5-4864 (4-chlorodiazepam), PK 11195 (1-(2-chlorophenyl)-1,3-dihydro-1-methyl
      propyl)isoquinoline carboxamide) and diazepam inhibit, in a concentration
      dependent way, the proliferation of V79 Chinese hamster lung cells (IC50 values
      were: 65.0 +/- 3.73 microM, 57.70 +/- 4.75 microM and 106.80 +/- 8.89 microM,
      respectively) without being cytotoxic. This antiproliferative effect is mediated
      by mitosis arrest in the G2 + M stage without affecting DNA synthesis and seems
      unrelated to a specific interaction of these drugs with the peripheral-type
      benzodiazepine receptor.

PMID- 7713172
TI  - Antidepressants reverse the olfactory bulbectomy-induced decreases in splenic
      peripheral-type benzodiazepine receptors in rats.
AB  - The present study investigated the effects of 21-day administration of clorgyline
      (1 mg/kg/day), desipramine (10 mg/kg/day) or paroxetine (10 mg/kg/day) on
      peripheral-type benzodiazepine receptors in rat peripheral tissues following
      bilateral olfactory bulbectomy. Thymus and spleen weights decreased as a result
      of bulbectomy. Subsequent antidepressant drug administration had no further
      effects on the weights of thymus glands but increased those of spleens. In thymus
      glands, higher densities of peripheral-type benzodiazepine receptors were
      observed in medulla than in cortex; no significant variations were observed
      following bulbectomy or antidepressant drug administration. In spleen, higher
      densities were observed in white pulp than in red pulp. The bulbectomy-induced
      decreases in binding densities observed in both regions were reversed following
      administration of antidepressants. Adrenal peripheral-type benzodiazepine
      receptors were not altered by bulbectomy or subsequent treatment with clorgyline
      or desipramine while paroxetine upregulated these receptors. No changes in kidney
      peripheral-type benzodiazepine receptors were observed. The present study
      confirms that cell lines of the rat immune system possess high densities of
      peripheral-type benzodiazepine receptor binding sites and further support the
      contention that, following olfactory bulbectomy, rats may present an
      antidepressant-reversible immunitary dysfunction.

PMID- 7713174
TI  - Inhibitory effects of Rb+ on the responses to levcromakalim and P1060 in the
      isolated human myometrium.
AB  - The mechanoinhibitory effects of two structurally dissimilar K+ channel openers,
      levcromakalim and P1060, and verapamil were compared in strips of human
      myometrium bathed in either K-PSS (normal Krebs solution) or Rb-PSS (K+ salts
      replaced by Rb+ equivalents). In Rb-PSS the effects of levcromakalim and P1060 on
      amplitude and frequency of spontaneous contractions were inhibited by more than
      20- and 138-fold, respectively, whereas those of verapamil were unaltered. These
      results indicate that K+ channel openers possess Rb-sensitive and Rb-insensitive
      mechanoinhibitory actions on the human uterus, the former being more important in
      the effects of P1060 than levcromakalim.

PMID- 7713175
TI  - Mathematical and analytical aspects of tracking.

PMID- 7713176
TI  - Vascular effects of chronic arsenic exposure: a review.

PMID- 7713177
TI  - Epidemiology of obstructive sleep apnea.
AB  - Sleep-disturbed breathing, which includes apneas, hypopneas, and oxygen
      desaturations, occurs in asymptomatic individuals and increases with age.
      Obstructive apnea is the most frequent type of respiratory disturbance documented
      by polysomonography, the gold standard test for assessing sleep-disturbed
      breathing. Many of the prevalence studies done to date have had one or more
      methodological weaknesses, including selection biases, varying definitions of
      obstructive sleep apnea, failure to distinguish types of apneas, failure to
      control for confounding variables, and small sample size. Although there is
      consensus on the definitions of sleep-disturbed breathing, the appropriate number
      of apneas and hypopneas for diagnosing clinically significant obstructive sleep
      apnea is uncertain. While the cutoff of five or more apneas and hypopneas per
      hour is historically considered abnormal, the origins of this number are vague,
      and the longevity of those who have this value on polysomnography is not
      necessarily reduced. This is particularly true among those without symptoms of
      obstructive sleep apnea syndrome, which include excessive daytime sleepiness,
      snoring, nocturnal awakenings, and morning headaches. Investigators should be
      careful to distinguish symptomatic study subjects from asymptomatic subjects, and
      to exclude central apneas in calculating their estimates. In addition, various
      studies have used different definitions of sleep apnea syndrome, making
      comparisons of point estimates difficult. It would be more appropriate for
      researchers to estimate morbidity and mortality indices with confidence
      intervals, using several different cutoff points. Subject selection in all
      studies should follow a two-stage sampling procedure. All subjects with symptoms
      compatible with obstructive sleep apnea syndrome and a subsample of asymptomatic
      individuals should be studied with all-night polysomnography. If portable
      monitoring is used, the validity and reproducibility of this diagnostic method
      should be assessed. Subjects with significant comorbidity should be excluded from
      prevalence studies. Factors that clearly increase the risk of sleep-disturbed
      breathing and obstructive sleep apnea and its related symptoms include age,
      structural abnormalities of the upper airway, sedatives and alcohol, and probably
      family history. Although endocrine changes such as growth hormone, thyroid
      hormone, and progesterone deficiency also have been suggested as risk factors for
      exacerbating obstructive sleep apnea syndrome, there is minimal epidemiologic
      evidence to support this. Case-control studies are recommended to assess the
      relation of endocrine factors to obstructive sleep apnea syndrome in a rigorous
      fashion. A limited number of mortality studies have suggested decreased survival
      in persons with the obstructive sleep apnea syndrome, possibly primarily due to
      vascular-related disease.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7713178
TI  - Definitions and determinants of handicap in people with disabilities.
AB  - Researchers have made a distinction between disability and its social and
      psychological consequences, now known as handicap, both conceptually and in terms
      of intervention. More work is needed in standardizing and refining the assessment
      of handicap and in highlighting risk factors for its development. Epidemiology
      has major contributions to make in understanding handicap in both aging and young
      populations. Data on the prevalence and incidence of handicap are scarce and
      difficult to obtain. Efforts are needed in the following areas: 1) contributing
      to the methodology of handicap assessment through the provision of valid and
      reliable scales; 2) defining and identifying risk factors for handicap formation,
      which underscores the need for analytic studies in this regard; 3) understanding
      the dynamics of these factors in the production of disadvantage, which calls for
      more qualitative and in-depth interviews with persons with handicaps; and 4)
      formulating critical points of intervention at the personal and community levels
      for handicap prevention. Such efforts will assist policy-makers in formulating
      appropriate and acceptable policies for safeguarding the opportunities of people
      with disabilities, ensuring their optimal participation in society, and enabling
      them to lead independent and self-sufficient lives. Efforts to evaluate the
      effect of legislation, both existing and recent, on handicap development are also
      called for. These efforts may help to reduce the gap between disabled and
      nondisabled people and improve the quality of life for people with disabilities
      and their families.

PMID- 7713179
TI  - Epidemiology of childhood leukemia, with a focus on infants.

PMID- 7713180
TI  - Epidemiology of colorectal adenomas.

PMID- 7713183
TI  - Monitoring for multiple congenital anomalies: an international perspective.

PMID- 7713182
TI  - Maternal cocaine use during pregnancy and perinatal outcomes.

PMID- 7713181
TI  - Reproductive history and coronary heart disease risk in women.

PMID- 7713184
TI  - Studies of the community and family: acute respiratory illness and infection.
AB  - Studies of acute respiratory illnesses in families and their communities have
      been carried out for most of this century. The initial studies established the
      importance of these illnesses in terms of their frequency and severity. Age
      specific illness rates and principles concerning disease transmission were
      documented in the period before identification of the etiologic agents. Since
      that time, the knowledge base has been expanded dramatically. Of all the viruses,
      rhinoviruses cause more illness of any severity than any other in all age groups.
      As a result, rates of rhinovirus-specific illnesses resemble those of all-cause
      respiratory illnesses. The greatest advantage of community-based studies is their
      ability to study transmission. Since control of infection for most of the agents
      has been difficult to achieve by conventional means, interruption of transmission
      should be examined as a possible alternative (97).

PMID- 7713185
TI  - Epidemiology of group B streptococcal disease. Risk factors, prevention
      strategies, and vaccine development.

PMID- 7713186
TI  - Surveillance of acquired immunodeficiency syndrome in Africa. An analysis of
      evaluations of the World Health Organization and other clinical definitions.

PMID- 7713187
TI  - Epidemiology of hepatitis B virus infections among injecting drug users:
      seroprevalence, risk factors, and viral interactions.

PMID- 7713188
TI  - Trends and patterns in the transmission of bloodborne pathogens to health care
      workers.
AB  - The key determinants of transmission of bloodborne pathogens are the dose and
      serum viral concentration of an exposure. This conclusion is supported by data
      showing that the rate of transmission of hepatitis B virus is elevated if the
      source patient's viral serum concentration is high and by a comparison of serum
      concentrations and rates of transmission for hepatitis B virus, HIV, and
      hepatitis C virus: As the mean serum viral concentration of each of these
      pathogens increases, the rate of transmission also increases. While there is
      evidence that the incidence of clinical hepatitis B has declined as a result of
      vaccine-induced immunity, the prevalence of hospital patients who are HBsAg
      positive has actually increased. As the AIDS epidemic evolves and increasing
      numbers of patients with AIDS are hospitalized, the risk of exposure to HIV and
      hepatitis B virus can be expected to increase further. Thus, health care workers,
      many of whom work in an urban setting and are exposed to the blood and body
      fluids of patients, should be required to receive hepatitis B vaccine. Whereas
      hepatitis B virus transmission can be prevented by immunization of health care
      workers, controlling hepatitis C virus and HIV will require efforts to reduce the
      incidence and dosage of exposures to blood and body fluids. These strategies
      include the design and use of safe medical devices, targeted interventions based
      on occupation-specific hazards, the use of gloves and other barriers, and ongoing
      surveillance and analysis of exposures in the health care setting.

PMID- 7713189
TI  - Inspiratory muscle training: where are we?

PMID- 7713190
TI  - Immune functions of constitutive pulmonary cells: the salt in the soup.

PMID- 7713191
TI  - Effect of Haemophilus influenzae endotoxin on the synthesis of IL-6, IL-8, TNF
      alpha and expression of ICAM-1 in cultured human bronchial epithelial cells.
AB  - Although studies of infective lung diseases have demonstrated that Haemophilus
      influenzae is a major pathogen, the mechanisms underlying pathogenesis by this
      organism are not clear. We have cultured human bronchial epithelial cells (HBEC)
      to confluency and have investigated the effect of H. influenzae endotoxin (HIE)
      on: 1) epithelial permeability, by movement of 14C-bovine serum albumin (14C-BSA)
      across HBEC and measurement of electrical resistance of HBEC; 2) release of
      interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF
      alpha) into the supernatant, by enzyme-linked immunosorbent assay (ELISA); and 3)
      expression of intercellular adhesion molecule-1 (ICAM-1), by immunofluorescence
      staining. HIE did not significantly increase the movement of 14C-BSA across HBEC.
      In contrast, HIE progressively increased the electrical resistance of HBEC, such
      that this was significant after 24 h. Compared with untreated cells, 10-100
      micrograms.ml-1 HIE-treated cells released significantly greater amounts of IL-6,
      IL-8 and TNF-alpha, after 24 h, which was blocked by 10(-5) M hydrocortisone.
      Similarly, incubation of HBEC with 10-100 micrograms.ml-1 HIE, significantly
      increased the total number of ICAM-1 positive cells, which were significantly
      decreased on incubation of the cells in the presence 10(-5) M hydrocortisone.
      Conditioned medium from HIE-exposed HBEC lead to significant increase in
      neutrophil chemotaxis and adhesion to endothelial cells in vitro. These results
      suggest that HIE may affect epithelial cell function and influence inflammation
      of the airway mucosa via induction of proinflammatory mediators.

PMID- 7713192
TI  - Effects of dexamethasone on cytokine and phorbol ester stimulated c-Fos and c-Jun
      DNA binding and gene expression in human lung.
AB  - Glucocorticosteroids have a wide variety of effects which result in the long-term
      dampening of inflammatory responses. An important site of steroid action may be
      on the control of the activator protein-1 (AP-1) binding to deoxyribonucleic acid
      (DNA). AP-1 is a proinflammatory transcription factor composed of a heterodimer
      of Fos and Jun proto-oncogenes, which can be induced by phorbol esters and
      various cytokines. We have examined the hypothesis that dexamethasone may inhibit
      inflammation via an effect on AP-1 activation in human lung tissue. The effect of
      dexamethasone on the phorbol ester and cytokine activation of AP-1 and its
      monomers was examined in human lung tissue obtained from transplantation donors.
      AP-1 activation was measured by its ability to bind DNA, its localization in the
      nucleus by Western blotting, and the levels of fos and jun messenger ribonucleic
      acids (mRNAs) using Northern blotting. The phorbol ester, phorbol myristate
      acetate (PMA), caused a significant 2-3 fold increase in AP-1 DNA binding, which
      was sustained for 24 h and completely attenuated by co-incubation with
      dexamethasone. Dexamethasone alone caused a 40% decrease in AP-1 DNA binding.
      Dexamethasone modulated the expression of both c-jun and c-fos mRNA and produced
      long-term (24 h) 40% reduction in both mRNAs when compared to control tissues.
      PMA induced a rapid and prolonged increase in c-Fos and c-Jun nuclear
      localization, which was not attenuated by co-incubation with
      dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713193
TI  - Suppression of T-cell activation by pulmonary alveolar macrophages: dissociation
      of effects on TcR, IL-2R expression, and proliferation.
AB  - Suppression of local T-cell activation in the lower respiratory tract by resident
      pulmonary alveolar macrophages (PAMs) is believed to play an important role in
      the maintenance of local immunological homeostasis. However, the mechanism(s) by
      which pulmonary alveolar macrophages regulate T-cell responses are poorly
      characterized. The present study examines early events during the activation
      process in mitogen-stimulated T-cell cultures, in which proliferation was
      completely blocked by the presence of pulmonary alveolar macrophages. Despite
      inhibition of proliferation, the T-cells demonstrated normal Ca++ flux, normal
      modulation of surface expression of CD3 and T-cell receptor alpha/beta (TCR
      alpha/beta), upregulation of interleukin-2 receptors alpha and beta (IL-2R alpha
      and IL-2R beta), and secretion of high levels of interleukin-2 (IL-2). Thus,
      pulmonary alveolar macrophage regulation of T-cell activation appears to permit
      initial expression of effector function, but selectively inhibits further
      amplification of the overall T-cell response by limiting clonal expansion of the
      activated effector T-cell.

PMID- 7713194
TI  - Nonresponse bias in EC Respiratory Health Survey in Italy.
AB  - In the three Italian centres involved in the European Community Respiratory
      Health Survey (ECRHS), prevalence of asthma-like symptoms was assessed through a
      mailback questionnaire. Since the nonresponse rate was not negligible, ranging 10
      18%, we investigated whether nonresponse bias affected the results and, if so,
      whether the bias could be eliminated from the final estimates of prevalence. A
      screening questionnaire was sent by mail to 7,000 randomly selected subjects 20
      44 yrs of age, and nonresponders were contacted again by phone. Additional
      information was collected on a subsample of the respondents through a clinical
      interview. A logistic regression analysis showed that, except for one symptom
      (awakening for coughing), symptom prevalence significantly decreased from the
      first to the subsequent contact, when controlling for age, sex, centre and season
      of interview. The decrease in symptom prevalence was largely independent of
      smoking habits and socioeconomic status, and was seemingly caused by a symptom
      related self-selection. When correcting results according to a linear regression
      model, observed estimates appeared to be slightly overestimated, by 4-10%. A
      simulation with the Italian data showed that the bias increased steeply at
      nonresponse rate higher than 30%, a situation quite common in asthma surveys. In
      conclusion, nonresponse bias affects the results of ECRHS in Italy, slightly
      inflating prevalence estimates. To make reliable comparisons on international
      data in the presence of different nonresponse rates, a correction of the observed
      prevalence seems necessary.

PMID- 7713195
TI  - Symptoms related to asthma and chronic bronchitis in three areas of Sweden.
AB  - Does the prevalence of respiratory symptoms differ between regions? As a part of
      the European Community Respiratory Health Survey, we present data from an
      international questionnaire on asthma symptoms occurring during a 12 month
      period, smoking and symptoms of chronic bronchitis. The questionnaire was mailed
      to 10,800 persons aged 20-44 yrs living in three regions of Sweden (Vasterbotten,
      Uppsala and Goteborg) with different environmental characteristics. The total
      response rate was 86%. Wheezing was reported by 20.5%, and the combination of
      wheezing without a cold and wheezing with breathlessness by 7.4%. The use of
      asthma medication was reported by 5.3%. Long-term cough and/or morning cough
      together with problems with phlegm was reported by 12.8%; the prevalence being
      highest in the most polluted area (Goteborg). When using multivariate analysis,
      no significant difference in asthma-related symptoms was found between the
      centres. Women reported cough more frequently, but otherwise gender did not
      influence symptom prevalence. Our results indicate that bronchitis symptoms occur
      more frequently in Goteborg, the most polluted of the Swedish centres, but that
      the prevalence rates of asthma-related symptoms do not differ between these three
      regions.

PMID- 7713196
TI  - Tidal breathing analysis and response to salbutamol in awake young children with
      and without asthma.
AB  - The purpose of the present study was to investigate: 1) whether tidal flow
      patterns can be used to discriminate between children with asthma and those
      without respiratory illness; and 2) whether reversibility to salbutamol in young
      children can be detected by tidal breathing analysis? Lung function was measured
      by tidal flow-volume loops (SensorMedics 2600) in 26 awake young children (13
      males) with asthma (aged 7-85 months; mean age 33 months), and 26 (13 males)
      (aged 3-72 months; mean age 34 months) without respiratory illness, before and 15
      min after inhalation of nebulized salbutamol, 0.05 mg.kg-1. The ratios of the
      time and volume until peak expiratory flow to the total expiratory time and
      volume, respectively, (TPEF/TE and VPEF/VE), and the ratio of tidal expiratory
      flow at 25% remaining expiration to peak expiratory flow, TEF25/PEF, were
      significantly lower in asthmatic children than in controls, and increased
      significantly after salbutamol inhalation in the former. Conversely, TPEF/TE and
      VPEF/VE, but not TEF25/PEF decreased significantly in the controls after
      salbutamol inhalation. Respiratory rate and expiratory volume.kg-1 body weight
      did not differ significantly between the two groups before and after salbutamol
      inhalation. We conclude that tidal breathing analysis can discriminate young
      children with asthma from children without respiratory illness, both regarding
      baseline lung function and reversibility to salbutamol.

PMID- 7713197
TI  - Incidence of acute decreases in peak expiratory flow following the use of metered
      dose inhalers in asthmatic patients.
AB  - This study aimed to investigate and compare the incidence of metered-dose inhaler
      (MDI)-associated bronchoconstriction in an asthmatic population, following the
      use of three different MDIs. Two different placebo metered-dose inhaler
      preparations containing the same chlorofluorocarbons but differing in dispersant
      chemicals, one containing oleic acid (MDI-OA) and the other lecithin NF (MDI-L),
      were compared with a MDI containing salmeterol xinafoate (25 micrograms) and
      lecithin NF (MDI-S). The study population comprised 11,850 asthmatic patients,
      who were assigned to receive two puffs from one of the three inhalers: MDI-S (n =
      3,948); MDI-L (n = 3,942); or MDI-OA (n = 3,960). Peak expiratory flow (PEF) was
      measured before and 5 min after inhalation. A 20% fall in PEF was defined as a
      clinically significant bronchoconstriction. Overall 180 (1.5%) patients
      demonstrated bronchoconstriction, 43 (1.1%) in the MDI-S group, 67 (1.7%) in the
      MDI-L group and 70 (1.8%) in the MDI-OA. A significantly lower incidence of
      bronchoconstriction was seen with the salmeterol xinafoate MDI compared to either
      of the other two preparations. The risk of acute bronchoconstriction was also
      shown to increase with age and with decreasing pretreatment PEF. The study has
      shown that acute bronchoconstriction is an uncommon adverse reaction following
      the use of metered-dose inhalers. In addition, the study suggests that one of the
      inert constituents currently within metered-dose inhalers is the likely source of
      the irritant leading to bronchoconstriction.

PMID- 7713198
TI  - Acute exacerbations of asthma in adults: role of Chlamydia pneumoniae infection.
AB  - Respiratory infections precipitate wheezing in many asthmatic patients and may be
      involved in the aetiopathogenesis of asthma. Several studies have demonstrated
      that viral infections may provoke asthma. Bacterial infections seem to play a
      minor role. However, Chlamydia pneumoniae has been recently reported as a
      possible cause of asthma. The aim of the present study was to evaluate the role
      of C. pneumoniae infection in acute exacerbations of asthma in adults. Seventy
      four adult out-patients with a diagnosis of acute exacerbation of asthma were
      studied. Acute and convalescent (> or = 3 weeks) serological determination of
      antibodies to cytomegalovirus, respiratory syncytial virus, adenovirus, influenza
      A and B, parainfluenza 1 and 3, Mycoplasma pneumoniae and Legionella pneumophila
      were performed by means of immunofluorescence tests. C. pneumoniae specific
      antibodies were detected by two microimmunofluorescence tests using a specific
      antigen (TW-183) and a kit with three chlamydial antigens. Pharyngeal swab
      specimens were also obtained for C. pneumoniae identification. Samples for
      bacterial culture were obtained in patients with productive cough (15 out of 74
      patients). Fifteen patients (20%) presented seroconversion to at least one of the
      studied pathogens. Seven were found to be infected by virus, six by C. pneumoniae
      alone, and one by M. pneumoniae. One more patient showed seroconversion to C.
      pneumoniae and cytomegalovirus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713199
TI  - Low plasma concentrations of VIP and elevated levels of other neuropeptides
      during exacerbations of asthma.
AB  - Neuropeptides in the lung occur in neurons, neuroendocrine and inflammatory
      cells. Their widespread distribution and physiological effects suggest that they
      may play important roles in asthma. We investigated whether, during an
      exacerbation of asthma, patients displayed changes in plasma levels of the
      neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related
      peptide (CGRP), substance P (SP), and neuropeptide Y (NPY). Venous blood from 25
      adult patients attending the emergency ward with an exacerbation of asthma was
      sampled before and after treatment. Plasma levels of VIP-, SP-, CGRP- and NPY
      like immunoreactivity (-LI) were determined by immunoassay, and the results
      obtained were compared with findings in 21 healthy controls. The mean plasma
      levels of VIP-LI were lower in patients (3.4 +/- 0.4 pmol.l-1) than in controls
      (10.4 +/- 0.7 pmol.l-1), whereas the levels of CGRP-LI (43.7 +/- 3.4 pmol.l-1),
      SP-LI (4.6 +/- 0.4 pmol.l-1) and NPY-LI levels (159 +/- 6 pmol.l-1) were higher
      in patients than in controls (21.1 +/- 3.4; 2.2 +/- 0.2 and 105 +/- 8 pmol.l-1,
      respectively). A relationship was seen between the reversibility of obstruction,
      expressed as improvement of peak expiratory flow upon treatment, and the
      neuropeptide levels, such that lower VIP-LI levels and higher CGRP-LI levels
      correlated with less reversibility. Plasma levels of neuropeptides, VIP-LI and
      CGRP-LI in particular, may therefore be employed as predictors of responsiveness
      to bronchodilatory therapy.

PMID- 7713200
TI  - The effects of indomethacin on refractoriness following exercise both with and
      without a bronchoconstrictor response.
AB  - Repeated exercise tests demonstrate refractoriness to the development of exercise
      induced asthma (EIA). It is unclear whether it is the initial exercise per se or
      the resulting bronchoconstriction that causes the attenuated response to the
      second exercise challenge. This study was designed to determine whether the
      reported blocking of the refractory period by indomethacin requires a significant
      bronchoconstriction following the primary exercise challenge. Thirteen asthmatic
      teenagers (aged 12-16 yrs) were tested on four visits. Each visit included two 7
      min treadmill exercise challenges at 80% maximum heart rate, separated by a 30
      min rest. Conditions for the second exercise challenge (Ch2) were always
      thermoneutral (20-22 degrees C and 25-35% relative humidity (RH); whilst
      challenge one (Ch1) was completed twice in thermoneutral and twice in warm-humid
      breathing conditions (33-35 degrees C and 90-95% RH). A pretreatment for 3 days
      in a double-blind design with either placebo or indomethacin was completed.
      Forced expiratory volume in one second (FEV1) was measured before and repeatedly
      following each challenge. The % fall in FEV1 following Ch1 of the placebo
      thermoneutral trial was taken as reference. "Percent protection" at each visit
      was expressed as the decrease in EIA following Ch2, compared to reference. Warm
      humid breathing reduced the EIA post Ch1 by 75%, whilst providing similar
      protection to thermoneutral conditions. Indomethacin had no significant effect on
      EIA after Ch1, but reduced "percent protection" for both warm-humid (from 67 to
      16%) and thermoneutral (from 70 to 26%) conditions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7713201
TI  - High-dose inhaled steroids in asthmatics: moderate efficacy gain and suppression
      of the hypothalamic-pituitary-adrenal (HPA) axis. Research Council of the
      Norwegian Thoracic Society.
AB  - We wanted to evaluate the improvement in efficacy when increasing the daily dose
      of inhaled steroids and to compare the efficacy, safety, and tolerance of 1.6 mg
      beclomethasone dipropionate (BDP) with that of 2.0 mg fluticasone propionate
      (FP). The study was a randomized, double-blind, 3 month, multicentre study. One
      hundred and thirty four asthmatics currently using inhaled steroids (0.4-1.6 mg
      BDP or budesonide (BUD)) were stratified according to pretrial daily steroid use.
      Within each stratum they were randomized to either 1.6 mg BDP or 2.0 mg FP. A
      significant increase in the primary efficacy variables, i.e. mean morning and
      evening peak expiratory flow (PEF) (approximately 20 l.min-1) during the
      treatment period, was found for both treatments. No significant differences
      between the drugs were revealed for these primary or any other secondary efficacy
      variables (use of beta 2-agonists, symptom scores, and PEF, forced vital capacity
      (FVC), forced expiratory volume in one second (FEV1) recorded at the clinical
      visits). However, significant differences between treatments occurred regarding
      decrease of serum cortisol and adrenocorticotropic hormone. We conclude that,
      although both treatments gave statistically significant increases in efficacy
      parameters when compared with baseline, the increases were so small that they can
      be regarded as being clinically unimportant. Daily doses of BDP, 1.6 mg, and FP,
      2.0 mg, had comparable effects on lung function. A suppression of the
      hypothalamic pituitary adrenal (HPA) axis was only found with a daily dose of 2
      mg FP.

PMID- 7713203
TI  - Slow and fast changes in transmural pulmonary artery pressure in obstructive
      sleep apnoea.
AB  - Our purpose was to assess how pulmonary artery pressure changes in relation to
      hypoxia and oesophageal pressure during obstructive sleep apnoeas. Transmural
      systolic pulmonary artery pressure (Ppa,STM), oxyhaemoglobin saturation (SaO2)
      and oesophageal pressure were analysed in two samples of consecutive obstructive
      apnoeas in each of four patients. In the first samples (samples A; probably
      recorded during non-rapid eye movement (NREM) sleep), SaO2 swings were small and
      repetitive. In the second samples (samples B; probably recorded during rapid eye
      movement (REM) sleep), they were large and more variable. Oesophageal pressure
      oscillated similarly in the two groups of samples. In all cases, transmural
      systolic pulmonary artery pressure progressively increased throughout apnoeas,
      and subsequently decreased in the interapnoeic periods. However, both early and
      end-apnoeic transmural systolic pulmonary artery pressure, remained stable in
      samples A; whilst they progressively increased in samples B. Transmural systolic
      pulmonary artery pressure at the beginning of each apnoea was inversely
      correlated with SaO2 at the end of the preceding apnoea. These results suggest
      that transmural systolic pulmonary artery pressure is influenced by SaO2, but
      does not vary at the same speed as SaO2. In all cases, beat-by-beat analysis
      showed, as expected, that the lower the oesophageal pressure, the higher the
      transmural systolic pulmonary artery pressure however, at each oesophageal
      pressure level, transmural systolic pulmonary artery pressure was more variable
      and higher, in samples B. In conclusion, transmural systolic pulmonary artery
      pressure in obstructive apnoeas shows rapid changes, which reflect oesophageal
      pressure variations, and slower changes, which are likely to be caused by SaO2.

PMID- 7713202
TI  - The influence of age on aerosol deposition in children with cystic fibrosis.
AB  - Nebulized aerosols are commonly used to deliver drugs for the treatment of
      respiratory disease in children, but there are inadequate data on the dose of
      drug depositing in the lungs in this age group, and the effect of age on this
      dose. We therefore aimed to quantify total and regional deposition of nebulized
      aerosol in children of widely differing age. Twelve infants (median age 0.8 yrs,
      range 0.3-1.4 yrs) who were asleep, and eight older children (median age 10.8
      yrs, range 6.3-18.0 yrs) with cystic fibrosis were studied. Radiolabelled normal
      saline aerosol was generated by a Turret nebulizer, with a driving flow of 9
      l.min-1. All subjects inhaled aerosol via the nasal route, whilst the older
      children undertook a second study with inhalation via the oral route. Following
      aerosol inhalation, planar and single-photon emission computed tomography (SPECT)
      scans were obtained. For the nasal route, total lung deposition was lower in
      infants (median 1.3%, range 0.3-1.6%) than in older children (median 2.7%, range
      1.6-4.4%). For the older children inhaling via the nasal or oral route, there was
      no influence of age on lung, upper respiratory tract, or the sum of upper
      respiratory tract and lung deposition. We conclude that the dose of a nasally
      inspired aerosol reaching the lungs of infants who are asleep is approximately
      half that for older children, when the nebulizer is operating at 9 l.min-1. Age
      does not affect deposition of nasally or orally inspired aerosols in older
      children.

PMID- 7713204
TI  - Longitudinal lung function study in heterozygous PiMZ phenotype subjects.
AB  - It is a matter of controversy whether subjects who are heterozygous (PiMZ) for
      alpha 1-antitrypsin deficiency are at risk of developing pulmonary emphysema. To
      assess the role of MZ phenotype in the development of abnormal lung function the
      authors performed a 10 year follow-up study of 28 PiMZ subjects, compared to 28
      matched-paired normal PiMM subjects. Maximal expiratory flows and mechanical
      properties of the lungs were studied, in order to determine the changes of the
      lung function parameters characteristic of pulmonary emphysema. Total lung
      capacity and residual volume increased, whereas forced expiratory volume in one
      second, expiratory flows, diffusing capacity of the lungs for carbon monoxide,
      and static transpulmonary pressures decreased in the PiMZ patients. The majority
      of the controlled functional parameters were found to deteriorate significantly
      in PiMZ patients during the 10 year period. Trypsin inhibitory capacity in the
      PiMZ group (mean +/- SD) was 0.65 +/- 0.17 mg.ml-1 as compared to 1.52 +/- 0.3
      mg.ml-1 in the PiMM group. These changes exceeded the values expected as
      physiological changes due to ageing. The findings in the present longitudinal
      study--especially the decrease in elasticity, which is the primary
      pathophysiological damage in alpha 1-antitrypsin deficiency--support the concept
      that the PiMZ phenotype is a risk factor for the development of pulmonary
      emphysema at younger age than in those without the deficiency.

PMID- 7713205
TI  - Effects of combined inspiratory muscle and cycle ergometer training on exercise
      performance in patients with COPD.
AB  - Cycle ergometer training plays an important role in the rehabilitation of
      patients with chronic obstructive pulmonary disease (COPD), but the usefulness of
      specific inspiratory muscle training as part of pulmonary rehabilitation remains
      uncertain. To determine whether inspiratory muscle training could intensify the
      known beneficial effects of cycle ergometer training on exercise performance in
      these patients, we compared the effect of an 8 week inspiratory muscle training
      combined with cycle ergometer training with that of an 8 week cycle ergometer
      training alone on inspiratory muscle performance and general exercise capacity.
      Patients were randomly assigned to the two training groups; 21 patients received
      additional inspiratory muscle training (Group 1) and 21 did not (Group 2).
      Maximal sniff assessed oesophageal and transdiaphragmatic pressures served as
      parameters for global inspiratory muscle strength and diaphragmatic strength,
      respectively. The duration for which the patient could breathe against a constant
      inspiratory pressure load was used as an index of inspiratory muscle endurance.
      Exercise capacity was determined by an incremental symptom-limited cycle
      ergometer test. After the training period, inspiratory muscle performance
      improved significantly in the patients with inspiratory muscle training, but not
      in those without. Both training regimens increased maximal power output and
      oxygen uptake, but this improvement was significantly greater in the patients
      with inspiratory muscle training than in those without.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7713206
TI  - Immune-inflammatory functions of fibroblasts.
AB  - Inflammation is a response that has evolved over millions of years to become an
      extremely complex process. This complexity reflects the host's need to deal
      effectively with a wide variety of potentially injurious agents, as well as the
      need to incorporate an adequate set of checks and balances. An inappropriately
      checked response, which occurs rarely, results in disease, either acute or
      chronic. However, in most instances, inflammation is a beneficial response,
      essential for survival. Inflammation comprises an extensive network of cellular
      interactions implemented by an overwhelming number of molecules. One category of
      signal includes soluble products, such as neuropeptide, lipid mediators,
      cytokines and growth factors, most of which can be produced by
      inflammatory/haemopoietic cells. However, resident structural cells can also
      produce many of these products and, on this basis only, fibroblasts, epithelial,
      endothelial and smooth muscle cells should be considered as active contributors
      to the regulation of the inflammatory response. Extracellular matrix (ECM)
      proteins comprise another category of signals. Whilst the most recognized
      activities of these proteins are those concerned with providing structural tissue
      integrity, it is clear that they also have powerful inductive effects. Indeed,
      ECM proteins can influence the shape, movement and state of activation of
      inflammatory cells in the tissue. Recent evidence indicates that these signals
      may also play substantial roles in homing of inflammatory cells to certain sites
      and in the handling of a number of cytokines and growth factors. In so far as
      fibroblasts are the main producers of ECM proteins, these new data establish an
      indirect but important role for fibroblasts in the regulation of the inflammatory
      response.

PMID- 7713207
TI  - Respiratory muscles during ventilatory support.
AB  - Knowledge of the fate and behaviour of the respiratory muscles during ventilatory
      support is important for the guidance of clinical care. Full support facilitates
      muscle metabolic repletion, but exposes them to the risk of disuse atrophy. The
      effect of partial support varies according to the selected mode: assisted
      mechanical ventilation (AMV) and synchronized intermittent mechanical ventilation
      (SIMV) result in much less respiratory muscle rest than generally anticipated. On
      the other hand, inspiratory pressure support (IPS) is able to rest the
      respiratory muscles and to prevent fatiguing contractions. Opposite interventions
      have been proposed in case of difficult weaning: either to unload the respiratory
      muscles by using partial support, or to overload them according to a training
      programme. The optimal strategy is not known and may combine both approaches.

PMID- 7713208
TI  - Proinflammatory potential of the airway epithelium in bronchial asthma.
AB  - Histopathological studies of asthmatic airways removed postmortem or by bronchial
      biopsy show marked inflammatory changes, notably epithelial cell disruption and
      damage, and the presence of large numbers of eosinophils. The epithelial damage
      is seen in mild, asymptomatic asthmatics as well as in patients who have died in
      status asthmaticus. Damage to the epithelium may also correlate with bronchial
      hyperreactivity. The epithelium has been suggested to be a target for
      inflammatory cell mediators and cytokines. Recently, the airway epithelium has
      itself been shown to produce and release several proinflammatory mediators and
      cytokines, and to express adhesion molecules for inflammatory cells. The
      epithelium, thus, may actively participate in the inflammatory changes in asthma,
      where it may be a source as well as a target. Drug therapy aimed at preventing
      inflammatory changes in the epithelium, such as cytokine and adhesion molecule
      expression, may be an important step forward in halting disease progression in
      asthma.

PMID- 7713209
TI  - The earliest history of diaphragm physiology.
AB  - The diaphragm was recognized as a distinct anatomical structure in the earliest
      Greek writings. However, the precise description of wounds suffered by warriors
      during the Trojan war by Homer was not tied to any particular function. The
      diaphragm was assimilated to the region that harbours thought. The first
      physiologic explanations of respiration by Empedocles in the 5th century BC and
      the concepts introduced by Plato and Hippocrates did not include a significant
      participation of the diaphragm. Aristole was the first to link respiration to a
      particular organ and a specific movement of the thorax. However, he considered
      that it was the heart which caused the lungs to expand by heating them, and the
      lungs in turn forced the thorax to dilate, a concept which was to survive until
      the 17th century. As in Aristole's theory the diaphragm played no role in
      respiration and was just a fence separating the thorax from the abdomen. A major
      break through occurred in Alexandria in the 4th and 3rd century BC: Herophilus
      was the first to recognize that muscles were the agents of movement and
      Erasistratus performed animal experiments which showed that the respiratory
      muscles were the agents of respiratory movements, thus opening the way to the
      later discoveries of Galen.

PMID- 7713210
TI  - Fourier analysis versus multiple linear regression to analyse pressure-flow data
      during artificial ventilation.
AB  - Respiratory resistance (Rrs) and elastance (Ers) are commonly measured in
      artificially-ventilated patients or animals by multiple linear regression of
      airway opening pressure (Pao) versus flow (V') and volume (V), according to the
      first order model: Pao = P0 + Ers.V + Rrs.V', where P0 is the static recoil
      pressure at end-expiration. An alternative way to obtain Rrs and Ers is to derive
      them from the Fourier coefficients of Pao and V' at the breathing frequency. A
      potential advantage of the second approach over the first is that it should be
      insensitive to a zero offset on V' and to the corresponding volume drift. The two
      methods were assessed comparatively in six tracheotomized, paralysed and
      artificially ventilated rabbits with and without adding to V' an offset equal to
      5% of the mean unsigned flow. The 5% flow offset did not modify the results of
      Fourier analysis, but increased Rrs and Ers from linear regression by 15.8 +/-
      4.6% and 4.55 +/- 0.64%, respectively. Without additional offset, differences
      between the two methods averaged 30.2 +/- 14.0% for Rrs and 9.3 +/- 6.2% for Ers.
      The differences almost completely disappeared (2.47 and 0.61%, respectively) when
      the flow signal was zero-corrected using the assumption that inspired and expired
      volumes were the same. After induced bronchoconstriction, however, Ers was still
      slightly larger by linear regression than by Fourier analysis, which may result
      from nonlinearities and/or frequency dependence of the parameters. We conclude
      that the regression method requires zero flow correction and that Fourier
      analysis is an attractive alternative.

PMID- 7713211
TI  - Necrobacillosis (Lemmiere's syndrome): a rare cause of necrotizing pneumonia.
AB  - The cases of four young and previously healthy patients with necrobacillosis are
      reported. All four patients presented with acute pharyngotonsillitis and
      pulmonary infiltrates due to metastatic abscesses, and had neutrophil
      leucocytosis and hypoalbuminaemia. Blood cultures grew Fusobacterium necrophorum
      and each patient responded to metronidazole.

PMID- 7713212
TI  - Bronchioloalveolar carcinoma with bronchorrhoea treated with erythromycin.
AB  - Recent reports have shown that erythromycin inhibits bronchial hypersecretion,
      and, accordingly, erythromycin was administered to a patient with
      bronchioloalveolar carcinoma with bronchorrhoea. After administration of
      erythromycin, marked reduction in the volume of sputum was observed, and the
      patient's quality of life was improved. It is concluded that erythromycin may
      reduce hypersecretion in bronchioloalveolar carcinoma.

PMID- 7713213
TI  - Unusual manifestations of giant cell arteritis: pulmonary nodules, cough,
      conjunctivitis and otitis with deafness.
AB  - The major manifestations of giant cell arteritis have been well described.
      Pulmonary manifestations, however, are rare. We report the case of a 75 year old
      woman with temporal arteritis, presenting with atypical manifestations, i.e.
      nodular pulmonary lesions, dry cough, rhinitis, conjunctivitis, and otitis with
      hearing loss. We conclude that overlapping features of giant cell arteritis and
      Wegener's granulomatosis occur in some patients.

PMID- 7713214
TI  - Effective use of cyclosporin in sarcoidosis: a treatment strategy based on
      computed tomography scanning.
AB  - Cyclosporin was used successfully in a patient with severe pulmonary sarcoidosis,
      a poor response and unacceptable side-effects from corticosteroid therapy.
      Computed tomography (CT) scanning initially suggested reversible disease, and
      subsequently detected improvement earlier than other indices of disease activity.
      This information was critical in the decision to commence and to continue
      cyclosporin. The literature on the use of cyclosporin in sarcoidosis is reviewed.

PMID- 7713215
TI  - Dyspnoea persisting after surgery for a vascular ring.
AB  - We present the case of a 25 year old woman who, 3 yrs after resection of a
      vascular ring, had persisting complaints of episodic dyspnoea. This was caused by
      compression of the distal trachea and ostium of the right main bronchus by the
      descending part of the remaining right-sided aorta. Probable mechanisms are
      discussed.

PMID- 7713216
TI  - Occupation and chronic obstructive pulmonary disease.

PMID- 7713217
TI  - [Correlation of dopamine and serotoninergic components in the neurochemical
      organization of the emetic mechanism].
AB  - It was found out in experiments on the pigeons that the destruction of
      serotoninergic neurons of the brain after preliminary introduction
      (intraventricular) of 5,6-dihydroxytriptamin blocked the development mechanism of
      emesis evoked by cisplatin and radiation action, but increased readiness to the
      development of emetic reaction evoked by apomorphine. On the other hand the
      destruction of dopaminergic neurons of the brain by 6-hydroxydopamine did not
      cause emetic condition by introduction emetic-causing substances (apomorphine,
      cisplatin, copper sulphate) and by X-ray even with a dose, which ensures 100%
      emetic effect (ED100) on the control group of pigeons. The mechanism of dopamine
      and serotonin participation in the neurochemical organization of the emetic
      mechanism is discussed.

PMID- 7713219
TI  - [Valentyna Vasylivna Radzymovska].

PMID- 7713218
TI  - [Role of non-protein factor of splenin in the regulation of antibody formation].
AB  - Non-protein factor of splenin that possesses T-mitogen activity under
      experimental conditions reproduces immunomodulatory action of the native drug in
      what concerns regulation of immunoglobulin synthesis. Premedication of CBA mice
      with the isolated factor increases primary immune response to ram erythrocytes by
      64%. When immediate allergic reaction develops in Wistar rats and BALB/c mice
      this factor suppresses IgE-antibody production via stimulation of suppressors T
      cells.

PMID- 7713220
TI  - [Individual adaptation of cardiovascular system in female swimmers, students of
      middle school].
AB  - Long trainings promote perfection of the regulatory mechanisms, that is
      characterized by an increase of cholinergic effects on the cardiovascular system
      of children. An optimal ratio of sympathetic and parasympathetic effects is
      typical of swimmer girls of different age with high level of working capacity in
      rest, that influences the adequate adaptation of the cardiovascular system to
      physical exercises. There are limits of adaptibility of the cardiovascular system
      of swimmer girls which is determined by informative indices of histogram. As
      influenced by physical exercises the favourable, incomplete favourable and
      unfavourable directions of the cardiovascular system shifts in swimmer girls are
      observed. Essential individual variations of the pattern of the functional
      changes in the cardiovascular system confirm the necessity to organize the
      training process allowing for the individual peculiarities of the development of
      children and adolescents.

PMID- 7713221
TI  - [Comprehensive approach to the evaluation of psychophysiological status in man].
AB  - Psychophysiological rating (PR) as an integral index of the human cognitive level
      has been evaluated in 95 pupils from senior classes using a set of 8
      psychophysiological parameters (QI, two indices of strength of the nervous
      system, functional mobility of the nervous processes, brain efficiency, speed and
      quality of analytical, logical and imagine mentality) determined by means of
      original computer programs. PR correlated with teaching efficiency (r = 0.535).
      It is offered to use PR for estimation of human cognitive level and professional
      selection.

PMID- 7713222
TI  - [Regression analysis of various results of hypercapnia test].
AB  - A comparative analysis of different statistic methods for determining individual
      reactivity of the respiratory system has been made. A mathematical model of
      ventilation dependence on partial pressure of carbon dioxide has been suggested.
      It has essential advantage as compared to those used before.

PMID- 7713223
TI  - [Effect of climate of arid zone on adaptive and non-adaptive changes in
      microcirculation].
AB  - State of microcirculatory bed of the bulbar conjunctiva and nail wall skin has
      been studied in 134 men (18-28 years old) of native (62 men) and non-native (72
      men) population. It was found out that under heat discomfort the compensation is
      observed in native population due to the induration of the capillary network,
      opening of plasmatic capillaries which did not function before, tonus of venules
      and arterioles being preserved while the amount of "gigantic" capillaries
      increased. In this case the blood flow was entire, uniform and moderately
      accelerated. The number of functioning capillaries does not increase in non
      native population, but arterioles does not increase in non-native population, but
      arterioles and venules were dilated, blood flow in them became more rapid, sludge
      phenomenon of the I stage being observed in some people. Consequently, the
      observed changes in microcirculation under heat discomfort are insignificant in
      the native population due to available structure-morphological potentialities,
      while in non-native population these changes are accompanied by certain strain at
      the expense of available functional reserves.

PMID- 7713225
TI  - [Absorption of vitamin B2 from plant and animal food products].
AB  - Assimilability of vitamin B2 from animal and plant foodstuffs has been studied in
      rats with plasma levels of free riboflavin and liver total riboflavin content as
      indices of B2 status. Studies have evaluated assimilability of vitamin B2 from
      diets containing buckwheat, oatmeal, dry milk, beef meat and liver.
      Assimilability of vitamin B2 from buckwheat and oatmeal was 40-70%, from milk
      80%, from meat liver about 90-100% of vitamin determined by chemical methods. The
      authors make a conclusion that control of vitamin B2 bioavailability from
      different products is necessary for calculation of vitamin content in rations
      from the tables of vitamin content in foodstuffs.

PMID- 7713224
TI  - [Effect of dietary animal fats on hormone concentration in the blood of female
      pigs and their offspring].
AB  - Piglet plasma insulin (I), cortisol (C), triiodothyronine (T3) and
      tetraiodothyronine (T4) levels have been studied for their dynamics depending on
      the age and metabolic energy in ration of pregnant sows. The considerable changes
      occur in the concentration of adaptive hormones in the piglet blood during 24
      hours after birth. The level of insulin in the piglet blood during the first day
      increases from 1.1 +/- 0.18 to 27.4 +/- 5.9 mkU/ml, whereas C, T3, T4 levels
      sharply decrease. There are no considerable differences in hormone concentration
      in the blood of older (5- and 21-day) piglets. It is established that insulin
      concentration in the blood of piglets increases 11, 7 and 2 times by the 0, 6,
      12th hours, respectively, after feeding pregnant sows with the ration containing
      nutrient animal fat. The 3- and 2-fold increase of T3 and T4 levels,
      respectively, was observed in the blood of newborn piglets from sows which
      received high fat ration. The influence of metabolic energy in the ration of
      pregnant sows at the level of T3 and T4 in the piglet blood also takes place at
      the later stages of neonatal development. It is supposed that piglets, whose
      mothers received extracaloric rations are more viable because of the changes in
      hormonal status in the neonatal period.

PMID- 7713226
TI  - [Tetrapolar rheoplethysmography in the quantitative evaluation of blood supply in
      extremities].
AB  - The method of forearm blood flow determination, based on the tetrapolar
      rheoplethysmography has been described. The technique offered allows one to
      characterize quantitatively the state of peripheric circulation. The method
      advantage is a simplicity and convenience of its use in physiological and clinic
      investigations.

PMID- 7713227
TI  - [Mechanisms of formation and action of polypeptide bio-regulators-- cytomedins ].
AB  - Possible mechanism of synthesis and effects of polypeptide bioregulative
      molecules (cytomedines) have been shown. This polypeptide has been obtained from
      different organs and tissues of animals. Its effects are supposed to be based on
      the processes of intercellular exchange and the cross-membrane transference of
      information signals. Synthesis of these molecules is considered as the limited
      proteolysis of protein structures. The information molecules of this kind will be
      found both inside and outside the cells. The evolution of regulative polypeptides
      was shown from the organisms of prebiotic era till contemporary organisms. The
      possibility of interaction between entigenic--endogenic peptides and regulative
      peptides is described. A hypothetic scheme of the effect of polypeptide molecules
      on the cell populations is suggested. Space interactions between proteins and
      polypeptides on the basis of the recognition codes of aminoacids can be most
      important factors.

PMID- 7713228
TI  - [Role of hypercholesterolemia in the pathogenesis of atherosclerosis].
AB  - The pathogenic role of hypercholesterolemia in the development of atherosclerosis
      was determined by investigation of the vessel's wall structural and functional
      peculiarities in rabbits, which were kept on atherogenic diet. It was evident,
      that even short duration of hypercholesterolemia led to significant disturbances
      of vascular reactivity, which manifested mainly in the inhibition of endothelial
      vasomotor activity against a background of the initial increase of smooth muscle
      sensitivity to contracting influences. These changes were almost the same in
      quality and magnitude in all the investigated sections of the vascular system
      including venous. After the prolonged periods of hypercholesterolemia these
      changes became much more pronounced but remained well spread through the whole
      system. The data of the electron microscopy confirmed both predominant
      disturbances of endothelial structure and their generalized character under the
      influence of hypercholesterolemia. These results indicate that
      hypercholesterolemia itself cannot create all the features of vascular
      atherosclerotic damage and that unlipid factors must be considered as not less
      important in its pathogenesis.

PMID- 7713229
TI  - [Effect of intracerebral administration of somatostatin and neurotensin on
      posture and movement disorders].
AB  - Experiments were performed on male Wistar rats to study posture-movement
      disorders after intracerebroventricular, intraamygdalar, intrahippocampal and
      intranigral (pars reticulata) injections of somatostatin and neurotensin.
      Development of movement disturbances characterized by changes in the posture
      movement syndrome was observed after somatostatin and neurotensin administration.
      Manifestation of movement disorders, their duration and the posture-movement
      syndrome structure depended on the structure to which neuropeptides were injected
      as well as on the neuropeptides themselves. Prolonged changes characterized by
      appearance of the so called "Sphinx" posture in animals developed after
      somatostatin intranigral administration. The obtained data permit concluding that
      somatostatin and neurotensin may have pathogenic significance in cataleptic
      syndrome development.

PMID- 7713230
TI  - [Effect of stress in early postnatal development on long-term changes in cellular
      immunity].
AB  - Using the model of colding stress in rats in early postnatal ontogeny, is has
      been established that the raise of PHA induced H-thymidine incorporation into the
      spleen cells and higher concentrations of corticosterone in the blood serum in
      adults. It is shown that stressing of animals (+5 + -0. +5 degrees C, 30 min) on
      the 4-9th day of postnatal life significantly alters the stress resctiveness in
      the adult animals.

PMID- 7713231
TI  - [Effect of chloditan on the changes of activity of glutathione transferase,
      glutathione reductase and glutathione content in the adrenal glands and liver in
      rats].
AB  - The chloditan (o.p-DDD, mitotane), which causes the destruction of the human and
      dog adrenal cortex, on the most essential system of xenobiotic metabolism:
      glutathione-S-transferase--glutathione has been studied. The effect of o,p-DDD on
      GSH level and activity of glutathione-S-transferase and glutathione reductase
      which maintain the level of reduced glutathione was analyzed in the adrenal and
      liver tissue of rats. This species is resistant to adrenocorticolytic action of
      o,p-DDD. It was shown that feeding of rats weighting 200-240 g with oil solution
      of o,p-DDD (75 mg daily) for 3 days causes the decrease in activity of
      glutathione-S-transferase and content of oxidazed glutathione in the adrenals
      with simultaneous increase of the content of reduced glutathione. The glutathione
      S-transferase and glutathione reductase activity in the liver rises under the
      effect of o,p-DDD, the decrease of the GSH level being observed. The revealed
      changes may explain the species sensitivity of animals to o,p-DDD.

PMID- 7713232
TI  - [Effect of acute stress on the changes of proteolytic processes in salivary
      glands in rats].
AB  - The general proteolytic activity and the level of proteinase inhibitors in
      salivary glands and blood serum of rats with acute stress were studied during the
      experiment. It was established that a trustworthy decrease of general proteolytic
      activity salivary gland homogenate was induced by activation of thermoacidstable
      inhibition in them.

PMID- 7713233
TI  - [Protective effect of vitamin E in acute administration of nitrobenzene and its
      chlorine derivatives into the stomach of rats].
AB  - The level of lipid peroxidation, content of vitamin E and its metabolites as well
      as antioxidative activity in the blood serum, liver and spleen of white rats were
      studied. Toxicological effects of nitrobenzene and nitrochlorbenzenes were
      decreased by vitamin E.

PMID- 7713234
TI  - Abortion for blindness.

PMID- 7713235
TI  - Doyne Lecture. The pathology of the outflow system in primary and secondary
      glaucoma.

PMID- 7713236
TI  - Biofilm-related infections in ophthalmology.
AB  - A biofilm is a functional consortium of microorganisms organised within an
      extensive exopolymer matrix. Organisms within a biofilm are difficult to
      eradicate by conventional antimicrobial therapy and can cause indolent
      infections. This paper reviews the pathophysiology of biofilms and their
      application of ophthalmology. Under certain environmental conditions such as
      nutrient limitation, some bacteria may secrete and reside in an exopolysaccharide
      glycocalyx polymer. This confers relative protection from humoral and cellular
      immunity, antibiotics and surfactants. Biofilms occur in natural aquatic
      ecosystems, on ship hulls, in pipelines and on the surface of biomaterials. They
      cause clinical infections of prosthetic hip joints, heart valves and catheters.
      Biofilm formation may occur rapidly on contact lenses and their cases and hence
      contribute to the pathogenesis of keratitis. Formation of biofilms is also
      implicated in delayed post-operative endophthalmitis and crystalline keratopathy.
      Bacteria within biofilms are 20-1000 times less sensitive to antibiotic than free
      living planktonic organisms. Existing experimental methods for modifying biofilm
      include the use of macrolide antibiotics that specifically impair biofilm
      production, and the use of enzymes to digest it. These may have clinical
      applications, as potential adjunctive therapies to antibiotic treatment, for
      these resistant infections. In conclusion, biofilm is an important cause of
      infections associated with biomaterials. Novel strategies are needed to deal with
      these.

PMID- 7713237
TI  - Toxicity of antibiotics and antifungals on cultured human corneal cells: effect
      of mixing, exposure and concentration.
AB  - Toxic effects of topical drugs may be masked by manifestations of the disease
      they cure. The toxicity of drug mixtures has not been thoroughly studied. We
      therefore investigated cytopathic effects on primary cultures of human corneal
      cells of six topical antimicrobials singly and in combinations of any two, to
      determine the combined toxicity ranking and the interaction between duration of
      exposure and concentration. Preconfluent cultures were exposed to fixed dilutions
      of single drugs, or to equal-dilution mixtures of two drugs, for 7 and 14 days.
      Diminishing concentrations of single drugs were applied sequentially to cultures
      for 14 days. The number of metabolically competent cells was assessed by
      measuring hexosaminidase and total protein. Toxic effects depended on substance,
      concentration and exposure. The scale of toxicity determined for single drugs
      after 7 days of exposure was: gentamicin > econazole > or = methicillin > or =
      clotrimazole > or = miconazole > or = chloramphenicol. After 14 days this order
      changed: in particular chloramphenicol showed a highly increased toxicity. The
      order of diminishing effects was: gentamicin > chloramphenicol > or = methicillin
      > miconazole > econazole > clotrimazole. A clear reduction in cytopathic effects
      was observed when drug concentration was decreased progressively only in cultures
      treated with gentamicin or methicillin. All drug combinations were more toxic
      than their components at equal dilution. Combinations containing chloramphenicol
      ranked most toxic overall, those containing econazole least. A tapering off
      combination regime did not improve cell survival. These in vitro toxicity data
      complement clinical studies and suggest ways in which topical drugs can be chosen
      to minimise toxic effects to corneal surface.

PMID- 7713238
TI  - Bacterial contamination of nylon corneal sutures.
AB  - We report the findings of a prospective study into the bacterial contamination of
      monofilament nylon sutures removed from corneal wounds following cataract
      surgery. Sutures were classified as tight, loose or broken at the time of
      removal. Loose and broken sutures showed significantly more bacterial
      contamination than tight sutures (p < 0.001, chi squared). Positive cultures were
      obtained from 2 (6.2%) of 32 tight sutures, 14 (38.9%) of 36 loose sutures and 11
      (37.9%) of 29 broken sutures. Staphylococcus epidermidis was the most commonly
      isolated organism (isolated in pure growth from 22 (81.5%) of 27 positive
      cultures). These findings may explain the occasional association of biodegraded
      corneal monofilament nylon sutures and suppurative keratitis and highlight the
      potential risk of seeding a suture track infection at the time of suture removal.
      They also emphasise the need for prophylactic topical antibiotic when removing
      biodegraded sutures.

PMID- 7713239
TI  - Familial posterior lenticonus.
AB  - Posterior lenticonus tends to be unilateral and there is no evidence that this is
      a familial condition. We report three cases of bilateral posterior lenticonus in
      boys. The mothers of all three cases had posterior lenticular changes, less
      severe than their sons. We suggest that bilateral posterior lenticonus may be
      inherited in an X-linked fashion.

PMID- 7713240
TI  - The Fasanella-Servat procedure: a retrospective study.
AB  - A retrospective study was carried out to assess the success of the Fasanella
      Servat procedure for the management of the aponeurotic defect type of adult
      ptosis. Eighteen procedures were carried out on 16 patients. The mean follow-up
      was 3 years. The success rate of the operation was 28% with a mean residual
      tarsal plate height of 5 mm with a very variable tarsal plate contour.

PMID- 7713241
TI  - Cannalicular occlusion with cyanoacrylate adhesive: a new treatment for the dry
      eye.
AB  - One hundred microlitres (0.1 ml) of N-butyl cyano-acrylate adhesive was injected
      into the inferior cannaliculus of 8 patients with dry eye. The adhesive induced
      total (upper and lower) cannalicular occlusion in each patient which has not
      resolved to date (mean follow-up 15.2 months, range 11-19 months). Complications
      were minor and not specific to use of this adhesive. It is hoped that its
      ultimate reversibility will make the technique suitable for younger patients with
      dry eye.

PMID- 7713242
TI  - Colour vision and side-effects during treatment with methazolamide.
AB  - The retina contains Na+K(+)-ATPase and carbonic anhydrase (CA), enzymes that
      regulate ion fluxes across cell membranes of photoreceptors. Since inhibition of
      retinal Na+K(+)-ATPase by digitalis impairs colour vision, we wanted to find out
      whether this also occurs after inhibition of CA. In a double-masked cross-over
      study with placebo, 14 male volunteers were given 50 mg q.i.d. of the CA
      inhibitor methazolamide for 2 weeks. A disturbance of colour discrimination was
      observed in 8 of the 14 subjects, in the classification phase of Lanthony New
      Color Test. The presence of the disturbance was not significantly correlated to
      the degree of acidosis or to other side-effects. Its mechanism could be
      interpreted as a specific effect of CA inhibition in the retina (or the visual
      cortex) calculated to more than 99.9%.

PMID- 7713243
TI  - Comparison of visual assessment tests in multiply handicapped children.
AB  - The aims of this study were to compare acuity estimates achieved with visual
      evoked potential (VEP) and acuity card techniques and to examine the success
      rates of each test in a group of multiply handicapped children. Subjects were 52
      children (3-183 months) with multiple handicaps associated with prematurity (n =
      17), congenital anomalies (n = 16), hypoxic insult (n = 10) and other disorders
      (n = 9). Success rates for completing the tests were: VEP 88% and acuity cards
      85% (Keeler or Cardiff). The acuity card tests were less likely to be
      successfully completed in the severely disabled (p < 0.05) and in those children
      with nystagmus (p < 0.05). When both acuity cards were successful, results agreed
      to within +/- 1.75 octaves. Acuity card thresholds were significantly correlated
      with VEP thresholds (p < 0.02), but thresholds achieved with VEPs were better in
      children with poor vision.

PMID- 7713244
TI  - Drug therapy in a murine model of Acanthamoeba keratitis.

PMID- 7713245
TI  - Management of superior limbic keratoconjunctivitis with botulinum toxin.

PMID- 7713246
TI  - The role of molecular genetics in the prenatal diagnosis of retinal dystrophies.
AB  - Inherited retinal dystrophies are important causes of incurable blindness in
      developed countries. Advances in molecular genetics promise significant
      improvements in their management. Immediate benefits of present knowledge are
      presymptomatic and prenatal diagnosis in selected cases. To study the predictive
      power of these techniques a simulated genetic risk estimation was undertaken in a
      cone-rod retinal dystrophy pedigree known to be linked to chromosome 19. Using
      data on five fully informative, flanking DNA markers, phenotype was correctly
      assigned with only a 2% probability of error. If the two most closely linked
      markers were found to be uninformative, this error probability remained
      unchanged. Using genetic risk calculations and direct mutation detection many
      retinal dystrophies could now be identified by prenatal diagnosis.

PMID- 7713247
TI  - Measurement of ocular blood flow velocity using colour Doppler imaging in low
      tension glaucoma.
AB  - The purpose of this study was to compare the velocity of blood flow and vascular
      resistance measured by colour Doppler imaging in the ophthalmic and central
      retinal arteries in 34 eyes of 34 patients (mean age 68.1 years) with low tension
      glaucoma (LTG) and 17 eyes of 17 age-matched normal controls (mean age 65.2
      years). The Acuson 128 machine (using a 7.5 MHz probe) was used to measure peak
      systolic velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI).
      The EDV of the ophthalmic artery (OA) in the LTG was significantly (p = 0.04)
      less than in the normal control group. There was a significant (p = 0.02)
      increase in the vascular RI of both the OA and central retinal artery in the LTG
      group compared with the normal controls. The OA RI increased with age (r = 0.61,
      p = 0.0001), and the OA EDV decreased with age (r = -0.50, p = 0.003), in the LTG
      group but not in the normal control group. The results suggest an increased
      resistance to blood flow in the ophthalmic and central retinal arteries of LTG
      patients.

PMID- 7713248
TI  - Dominantly inherited drusen represent more than one disorder: a historical
      review.
AB  - Hutchinson-Tay choroiditis, Holthouse-Batten chorioretinitis, Doyne's honeycomb
      familial choroiditis and Malattia levantinese are various names which have been
      used to denote dominantly inherited drusen. Whether these represent one or more
      than one disorder remains unclear because of the quality of the illustrations and
      incomplete information in some of the original articles. The early descriptions
      of these various conditions have been reviewed. Evidence is presented that
      Doyne's honeycomb familial choroiditis and Malattia levantinese are disorders
      which can be distinguished from each other by clinical criteria.

PMID- 7713249
TI  - Foveal involvement and lack of visual recovery in APMPPE associated with uncommon
      features.
AB  - Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is commonly
      believed to be a benign disease with excellent visual prognosis. Identification
      of cases with poor visual outcome prompted this retrospective study of 33 eyes of
      18 patients with this disorder. Loss of visual acuity at presentation was
      recorded in 25 eyes (76%), 22 of which had lesions at the fovea. Visual acuity
      quickly returned to normal or near normal levels (even when it was as poor as
      counting fingers at entry) in all but 7 eyes of 7 patients, in which visual
      acuity failed to recover to better than 6/24 over a period of several months. All
      these eyes had poor acuity and foveal involvement when first seen, and at least
      one of the following atypical features: age older than 60 years, unilaterality,
      an interval before involvement of the second eye of at least 6 months, recurrence
      of the disease, leakage from choroidal vein. One additional patient whose foveae
      were initially not involved lost vision in one eye because of the development of
      choroidal neovascularisation. Caution should be exercised in giving a prognosis
      in cases when the fovea is involved and the acuity markedly reduced, particularly
      if one or more atypical features is present.

PMID- 7713250
TI  - Quantitative image analysis of macular drusen from fundus photographs and
      scanning laser ophthalmoscope images.
AB  - Drusen are common features in the ageing macula and are associated with exudative
      age-related macular degeneration (ARMD). They appear as characteristic structures
      in indirect mode infrared scanning laser ophthalmoscope (SLO) images. Manual
      counting of drusen area in SLO images has shown no significant difference from
      that in standard fundus photographs in 6 eyes of 5 patients (p > 0.5).
      Computerised image processing techniques have been applied to digitised colour
      fundus photographs and indirect mode images to quantify the area of the macula
      affected by drusen in an automated fashion. Application of these methods may
      permit objective and repeatable assessment of the natural history of macular
      drusen. For a specificity of 90%, a sensitivity of 60% for colour fundus
      photographs and 35% for SLO images has been achieved, when compared with manual
      counting. The colour fundus photograph method also showed superior
      reproducibility compared with the SLO technique.

PMID- 7713251
TI  - Immunophenotyping in presumed ocular histoplasmosis like retinopathy.
AB  - Four cases of presumed ocular histoplasmosis like retinopathy are presented. A
      detailed immunological assessment was carried out on the patients and a control
      group: lymphocyte immunophenotyping; flow cytometric analysis; HLA typing and T
      cell receptor variable region (TCR V region) expression were assessed. Analysis
      of TCR V region expression revealed no significant preferential expression. HLA
      typing also failed to reveal any links. All lymphocyte markers analysed were
      unremarkable, with the exception of CD38 which was significantly raised compared
      with controls (p < 0.01). This finding was confirmed by the use of two different
      CD38-specific monoclonal antibodies. The raised CD38 in our cases was shown to be
      persistent when the patients were retested after an interval of several months.
      Significantly, this may correlate with poor T cell function, as in Common
      Variable Immunodeficiency, making these patients more susceptible to various
      stimuli.

PMID- 7713252
TI  - Risk of bilateral idiopathic preretinal macular fibrosis.
AB  - To ascertain the risk of the development of bilateral idiopathic preretinal
      macular fibrosis, we retrospectively studied 380 consecutive patients with
      idiopathic preretinal macular fibrosis. Eighty (21%) patients had bilateral
      involvement. Sixteen (39%) of 41 patients with diabetes, 40 (28%) of 144 with
      hypertension, and 12 of 21 (57%) with bilateral high myopia had bilateral
      involvement. The prevalence of bilateral involvement was significantly higher in
      patients with these three pathologies than in patients without these conditions
      (p < 0.01, p < 0.02 and p < 0.01, respectively). In patients with diabetes or
      hypertension, no significant difference was found in the prevalence of posterior
      vitreous detachment (PVD) between involved or uninvolved eyes. Diabetes,
      hypertension even without retinopathy, and high myopia may be risk factors for
      bilateral involvement of idiopathic preretinal macular fibrosis. Factors other
      than PVD may be involved in the development of idiopathic preretinal macular
      fibrosis in patients with diabetes or hypertension.

PMID- 7713253
TI  - Imaging of optic disc drusen: a comparative study.
AB  - The choice of imaging technique to identify the presence of optic disc drusen has
      not been well established. We performed computed tomography (CT), magnetic
      resonance imaging (MRI), fundus fluorescein angiography and B-mode
      ultrasonography (B-USG) on four patients with optic disc drusen as the sole
      identifiable pathological process. CT, MRI and examination for autofluorescence
      demonstrated the presence of drusen in only one case each. B-USG showed
      characteristic features of optic disc drusen in all cases. We suggest that B-USG,
      a non-invasive and inexpensive technique, may be the imaging method of choice in
      identifying the presence of disc drusen.

PMID- 7713254
TI  - Quantitative analysis of retroillumination images.
AB  - We have developed a semi-automated image processing system for analysis and
      evaluation of retroillumination images. This paper describes methods used to
      compensate for illumination variations in the images, separation of data into
      cataractous and non-cataractous portions, how quantitative measurements are made
      and how they assess the pathological condition. In addition to the traditional
      area measurement, this system computes the net integral of density and several
      measurements involving the location of the opacity in relation to the pupillary
      margin. The computer measures of area, integral of density, area centrality,
      weighted area, density centrality and weighted density provide more data than
      previously described systems. Data produced by this interactive and automated
      system can be used in studies of posterior subcapsular and cortical cataracts,
      and to study the effect of these opacities on vision.

PMID- 7713255
TI  - Fibrinogen, cholesterol and smoking as risk factors for non-arteritic anterior
      ischaemic optic neuropathy.
AB  - Non-arteritic anterior ischaemic optic neuropathy (AION) is thought to be due to
      occlusion of the posterior ciliary circulation. Raised lipid and fibrinogen
      concentrations are recognised risk factors for vessel occlusion in cardiovascular
      disease and stroke but, although suspected as risk factors in non-arteritic AION,
      they have not been studied in this condition. We therefore performed a case
      control study on 41 patients with non-arteritic AION, looking at these and other
      atherosclerotic risk factors. The odds ratio of cholesterol being > 6.5 mmol/l in
      non-arteritic AION was 2.7 (95% confidence interval 1.09 to 6.65; p < 0.05) and
      of fibrinogen being > 3.6 g/l was 5 (2.66 to 9.39; p < 0.05). Smoking was also
      found to be significantly associated with non-arteritic AION, the odds ratio
      being 16 (3.23 to 79.23; p < 0.001). These were the only risk factors found to be
      significantly associated with non-arteritic AION. This raises the possibility
      that appropriate medical management of these factors could be given to prevent
      recurrence in the fellow eye.

PMID- 7713256
TI  - Immunisation against HSV-1 keratitis with a synthetic gD peptide.
AB  - The authors tested the protective efficacy of, and the immune response to,
      immunisation with a synthetic peptide of glycoprotein D (gD) of HSV-1 in a murine
      model of herpes stromal keratitis (HSK). HSV-1 susceptible A/J mice were
      immunised subcutaneously with a peptide corresponding to the N-terminal epitope
      gD(5-23) prior to corneal HSV-1 challenge. Divergent immunisation protocols were
      compared for their protective potency, their ability to prevent the establishment
      of latency in the trigeminal ganglion, and their effect on the immune system. Low
      dosages (31 micrograms) of gD(5-23) protected against encephalitis and HSK.
      Protective efficacy was higher when gD(5-23) was coupled to the carrier protein
      keyhole limpet haemocyanin (KLH) and was emulsified with adjuvant. Latent
      infection was found in all control mice but in only 50-75% of immunised mice. The
      most potent protection was correlated with anti-HSV-1 neutralising antibodies of
      IgG1 and IgG2a isotypes, but free gD(5-23) protected in the absence of anti-HSV-1
      antibodies. Our results suggest that immunisation with gD(5-23) stimulates both
      humoral and cellular immune mechanisms which protect against HSV-1 keratitis.

PMID- 7713257
TI  - Acute orbital myositis.
AB  - We examined 9 consecutive cases of unilateral orbital myositis (7 women and 2
      men; age range 15-46 years) presenting to Casualty. Only 3 were correctly
      diagnosed on the first visit. Eight patients exhibited globe retraction in the
      acute stages and, after treatment with systemic steroids, all made a full
      recovery. None of the patients had associated systemic disease and all remain
      well over a 6-12 month follow-up period. Orbital myositis may be a more common
      condition than previously thought; it can present with a variety of clinical
      signs, and may be difficult to diagnose in the early stages. The presence of
      globe retraction on movement of a painful, injected eye is a useful diagnostic
      sign which indicates inflammation of extraocular muscles and is present in the
      acute stages of the disease; we explain how to elicit globe retraction and
      suggest a management protocol for these patients.

PMID- 7713258
TI  - Comparative toxicity of certain mosquitocidal compounds to larvivorous fish,
      Poecilia reticulata.
AB  - Toxicity of certain mosquitocidal compounds (both larvicides and adulticides) to
      the larvivorous fish Poecilia reticulata was determined in the laboratory. Among
      the various chemical insecticides tested, the synthetic pyrethroid deltamethrin
      was most toxic to fish (LC50 = 0.016 ppm), while the organophosphorus insecticide
      abate was least toxic (LC50 = 34 ppm). The bioinsecticides Spherix (Bacillus
      sphaericus) and Bactoculicide (Bacillus thuringiensis H-14) showed highest safety
      for the fish (LC50 > 1000 mg/litre). Integrated use of larvivorous fish and
      bioinsecticide in vector control has been suggested.

PMID- 7713259
TI  - Correlation of malaria endemicity with An. culicifacies sibling species
      composition and malaria antibody profile in district Allahabad (U.P.).
AB  - Entomological, parasitological and serological surveys were conducted between
      October 1989 and November 1990 in 27 villages (population 33,250) belonging to
      three topographically different areas of district Allahabad, viz. Gangapar, Doaba
      and Yamunapar. A good correlation existed in all the three areas between malaria
      incidence vis-a-vis An. culicifacies sibling species composition and malaria
      antibodies titre in the populations. In Gangapar and Doaba villages, An.
      culicifacies densities were low and the proportions of vector species A and C
      were much less than that of species B, the non-vector species. Low endemicity of
      malaria was supported by low antibody titres observed in the population. In
      contrast, in Yamunapar villages An. culicifacies densities were high, species A
      and C together were almost equal to species B, and malaria incidence as well as
      antibody titre were high. Based on these observations, district Allahabad, Uttar
      Pradesh, could be divided into two zones, low malaria transmission zone--Gangapar
      and Doaba areas and high malaria transmission zone--Yamunapar area.

PMID- 7713260
TI  - Field trial of esbiothrin-impregnated rope in Ramgarh village, Dadri PHC,
      District Ghaziabad (U.P.).
AB  - A village-scale field trial was carried out to assess the operational feasibility
      and efficacy of smouldering 250 ppm esbiothrin-impregnated rope in repelling
      mosquitoes and its impact on transmission of malaria. Entomological monitoring
      revealed that smoke from smouldering rope resulted in 67.2-97.9% reduction of An.
      culicifacies densities in human and mixed dwellings. The reduction was obviously
      due to diversion of An. culicifacies population to cattlesheds where ropes were
      not burnt. The impact was more pronounced when indoor mosquito landing rate on
      human bait was compared with that of experimental and control areas. This was
      also reflected in reduced anthropophilic index and curtailment of malaria
      transmission in experimental area.

PMID- 7713261
TI  - Biology of malaria vectors in central Gujarat.
AB  - Biology of malaria vectors were studied in Kheda district of central Gujarat in
      order to understand the vector behaviour in the wake of ecological changes.
      Anopheles culicifacies and An. stephensi were mainly endophilic whereas An.
      fluviatilis exhibited marked exophily. All the three vectors were predominantly
      zoophilic. Peak biting activity period of An. culicifacies varied with season
      though biting continued in varying magnitudes throughout the night. An. stephensi
      and An. fluviatilis were arhythmic in their biting activity. Survival of all the
      three vectors was maximum during cold season owing to longer gonotrophic cycle
      which also yielded higher estimates for expected infective life. Instability of
      malaria in this area was probably due to low estimates of expected infective life
      for the three vectors. A wide range of breeding habitat preferences by An.
      culicifacies was observed whereas An. fluviatilis and An. stephensi showed
      restricted distribution.

PMID- 7713262
TI  - Oxidative stress and malaria-infected erythrocytes.
AB  - This paper presents several mechanisms/pathways by which oxidative stress could
      cause damage to the parasites. During developmental stages of plasmodia profound
      alterations of the structure and function of host erythrocytes take place, in
      order to support the development and/or survival of the parasite. In addition an
      oxidant stress is also induced by the parasite. There is also an increased
      production of reactive oxygen species (ROS) by the parasite. This may deplete the
      erythrocyte of its defense mechanisms namely, superoxide dismutase (SOD),
      catalase, glutathione peroxidase, NADPH, NADH, glutathione (GSH) and glutathione
      reductase etc. Thus oxidative stress may be exerted by the growing parasite in
      red blood cells which are highly sensitive to such a challenge. These enhanced
      alterations may result in a retarded development of the parasite. Thus, the
      coexistence of both parasite and erythrocyte is a matter of a delicate balance.
      However, one cannot rule out the role of external modulations (immune pressure)
      inhibiting the vitality of the parasites.

PMID- 7713263
TI  - A note on Anopheles culicifacies sibling species composition in stone quarry belt
      of district Allahabad (U.P.).

PMID- 7713264
TI  - High level chloroquine resistance of Plasmodium falciparum in Madras, Tamil Nadu.

PMID- 7713265
TI  - Resting and biting habits of Anopheles sundaicus in Car Nicobar Island.
AB  - Resting and biting habits of An. sundaicus were studied in Car Nicobar Island.
      Results of resting behaviour revealed that although substantial numbers of An.
      sundaicus rest outdoor, still the species prefer to rest indoors, and much less
      in human dwellings. High parity rate (73.38%) in An. sundaicus and close contact
      with man were the factors responsible for high transmission in Car Nicobar. An.
      sundaicus population in Car Nicobar is susceptible to DDT. Indoor man-biting of
      An. sundaicus was significantly higher than outdoors and the species showed
      bimodal biting activity with first peak between 2130 to 2230 hrs and second
      between 0130 to 0230 hrs. An. sundaicus preferred to feed on people's legs and
      hands. Due to complex behaviour of An. sundaicus, an integrated approach
      comprising (i) chemical, (ii) bioenvironmental control, and (iii) personal
      protection methods was suggested to interrupt malaria transmission in Car Nicobar
      Island.

PMID- 7713266
TI  - Distribution and relative prevalence of anophelines in district south 24
      Parganas, West Bengal, India.
AB  - The anopheline survey of district South 24-Parganas revealed presence of sixteen
      species including Anopheles annularis, An. subpictus, An. fluviatilis, An.
      varuna, An. culicifacies and An. sundaicus known to be associated with malaria
      transmission in the country. A total of 14, 12 and 8 species were encountered in
      cattlesheds (CS) in contrast to 7, 5 and 4 species in human dwellings (HD) during
      monsoon, winter and summer respectively. The population density of anophelines in
      CS was significantly higher than in HD in all the three seasons.

PMID- 7713267
TI  - Field evaluation of mosquito repellent action of neem oil.

PMID- 7713268
TI  - Epidemiological study of malaria outbreak in a hotel construction site of Delhi.

PMID- 7713269
TI  - Man biting rate of culicine mosquitoes in Cochin city.

PMID- 7713270
TI  - Feasibility study of insecticide-impregnated bednets for malaria control in
      forested villages of district Mandla (M.P.).

PMID- 7713271
TI  - Repellent action of Cymbopogan martinii martinii Stapf var. sofia oil against
      mosquitoes.
AB  - Studies were carried out to evaluate the repellent action of Cymbopogan martinii
      martinii Stapf var. sofia (F. Gramineae) against mosquitoes under field
      conditions. Results revealed that the oil has strong repellent action and
      provided absolute protection for 12 h against Anopheles culicifacies, a principal
      vector of malaria in the country. Similar degree of protection was evident
      against An. annularis and An. subpictus. The protection against Culex
      quinquefasciatus, a pest mosquito was 96.3% for 12 h. Results of evaluation in
      captivity revealed complete protection against this species for 5 h.

PMID- 7713272
TI  - Hypoglycaemia, the most feared complication of insulin therapy.
AB  - Insulin-induced hypoglycaemia, the most frequent side-effect of insulin-therapy,
      is a potential source of considerable morbidity and has a recognised mortality.
      Acute hypoglycaemia produces an intense physiological stress with profound
      sympathoadrenal stimulation and widespread activation of hormonal
      counterregulatory systems, leading to secondary haemodynamic and haemorheological
      changes. The clinical effects of acute and recurrent severe hypoglycaemia are
      associated with significant morbidity including reversible, and permanent,
      abnormalities of cardiovascular, neurological and cognitive function, in addition
      to trauma and road traffic accidents. Comprehension of the morbidity of
      hypoglycaemia is important when designing insulin regimens and determining
      therapeutic goals for individual patients if the frequency and adverse effects of
      this dangerous side-effect of insulin therapy are to be limited.

PMID- 7713273
TI  - Increased prevalence of soft tissue hand lesions in type 1 and type 2 diabetes
      mellitus: various entities and associated significance.
AB  - Sixty Type 1 (insulin dependent) and sixty Type 2 (non insulin dependent)
      diabetic patients attending a diabetology unit were examined in search of limited
      joint mobility, Dupuytren's disease, flexor tenosynovitis and carpal tunnel
      syndrome, in comparison with two populations of 60 non diabetic controls matched
      for sex and age with the Type 1 and the Type 2 diabetic patients.
      Microangiopathic and neuropathic complications, glycaemic control, blood pressure
      and tobacco consumption were simultaneously assessed in 39 of the 60 type 1 and
      in all the type 2 diabetic patients. The prevalence of the various soft tissue
      hand lesions was higher in both diabetic populations (respectively Type 1 and
      Type 2) than in their control populations: Limited joint mobility: 33.3 and 26.7%
      vs 5.0 and 8.3% (both p < 0.01); Dupuytren's disease: 35.0 and 30.0% vs 6.7 and
      10.0% (both p < 0.01); flexor tenosynovitis: 23.3 and 16.7% vs 0.0 and 3.3% (p <
      0.01 and p < 0.05); carpal tunnel syndrome: 26.7 and 15.0% vs 3.3 and 5% (p <
      0.01 and NS). The prevalence of limited joint mobility in Type 1 diabetes was
      independently associated with increasing age (p < 0.05) and to lower extent with
      increasing duration of diabetes (p = 0.05), whereas the prevalence of Dupuytren's
      disease only correlated with increasing age in both types of diabetes (p < 0.05).
      In Type 2 diabetes, the prevalence of flexor tenosynovitis also increased
      independently with age (p < 0.05), and the prevalence of limited joint mobility
      increased in the opposite way to the body mass index after adjustment on age,
      duration of diabetes and sex (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713274
TI  - Lipoprotein (a) and other risk factors in children with insulin-dependent
      diabetes mellitus and children without diabetes.
AB  - AIMS: To study serum Lp(a) levels and other metabolic cardiovascular risk factors
      in children with Type 1 diabetes mellitus (DM) compared to sex and age matched
      nondiabetic children. The correlation of Lp(a) serum levels and other lipid
      parameters with HbA1c concentrations in diabetic children was investigated.
      DESIGN: Transversal observational study. TARGET POPULATION: 36 C-peptide negative
      Type 1 DM children without microalbuminuria and no macromicrovascular or
      neurological complications, aged 8 to 15 years; 17 boys, 19 girls. Mean duration
      of Type 1 DM was 4.99 +/- 3.04 years, daily insulin need were 32.79 +/- 12.64
      Units. 41 healthy children with no family history of DM, aged from 8 to 15 years,
      26 boys, 15 girls, were studied in parallel as the control group. METHODS: Serum
      total cholesterol (TC) and triglycerides (TG) were assayed by enzymatic methods,
      high-density lipoprotein (HDL) cholesterol by enzymatic method after
      precipitation of very-low-density (VLDL) and low-density lipoprotein (LDL)
      fractions. The LDL fractions was estimated after serum precipitation as the
      difference between total cholesterol and supernatant cholesterol concentrations.
      Apo-AI, apo-AII and apo-B were measured by radial immunodiffusion assays. Serum
      Lp(a) was measured by monoclonal anti-Lp(a) antibody (ELISA) method and whole
      blood glycosylated hemoglobin A1c (HbA1c) by high resolution liquid
      chromatography. RESULTS: HbA1c concentration in diabetic children was 7.51 +/-
      54% vs 4.16 +/- 0.35% in non diabetic children. Lp(a) serum levels did not
      significantly differ among both groups (25 +/- 22 mg/dl in diabetics subjects, 22
      +/- 22 mg/dl in controls). Significant correlation was found between HbA1c levels
      and each of TC, LDL and TG serum concentrations in the diabetic group. Lp(a)
      levels were correlated with glycated hemoglobin in the whole diabetic group. But,
      in the 2 patients with the poorest metabolic control (HbA1c 10.5%) were excluded,
      the correlation disappeared. CONCLUSIONS: In 36 children aged 5-15 years with
      uncomplicated Type 1 DM lasting less than 15 years, Lp(a) serum levels did not
      differ from age-matched controls but highest Lp(a) values were associated with
      poorest metabolic control.

PMID- 7713275
TI  - Lack of relationship between Lp(a) particle levels and albumin excretion rate in
      type 1 diabetic patients.
AB  - The excess risk of cardiovascular disease in Type 1 diabetes mellitus compared to
      non diabetic subjects is only partially explained by standard risk factors.
      Several studies suggest that Lp(a) concentrations are increased in Type 1
      diabetes mellitus, but data are still controversial. Moreover, a high
      cardiovascular risk has been reported in diabetic patients with persistent
      proteinuria. Therefore, the aim of this study was to compare the Lp(a) particle
      levels in insulin-dependent diabetic patients with or without increased urinary
      albumin excretion. Cross-sectional study of Lp(a) plasma levels in a population
      of 140 insulin-dependent diabetic patients: 83 without increased proteinuria, 14
      with borderline elevation of urinary albumin excretion, 27 with micro- and 16
      with macro-proteinuria. Simultaneous determination of plasma lipids, fasting
      blood glucose and HbA1c was performed. The mean plasma Lp(a) concentrations and
      the distribution of the levels were comparable in all of the diabetic patient
      groups. No relationship existed between Lp(a) and HbA1c, fasting blood glucose or
      any lipid plasma levels. No influence of albumin excretion rate on Lp(a) levels
      was observed. These data provide no evidence of a specific contribution of Lp(a)
      particles to the increased morbidity and mortality from cardiovascular disease
      observed among patients with nephropathy.

PMID- 7713276
TI  - Metabolic and drug distribution studies do not support direct inhibitory effects
      of metformin on intestinal glucose absorption.
AB  - In an attempt to clarify the question of an involvement of the inhibition of
      intestinal glucose absorption in the mechanism of action of Metformin, we used
      several experimental approaches: 1 glucose/lactate measurement in rat portal
      blood in vivo and 2 in the venous effluent of an isolated perfused rat intestinal
      segment; 3 metabolism of freshly isolated enterocytes in vitro and tissue
      distribution of 3H-labeled Metformin was investigated both in vivo and in vitro.
      Metformin applied intraluminally had no significant effect on portal glycaemia
      after a glucose load, but lactate increased, whereas in vivo only a high
      Metformin dosage reduced portal glucose appearance significantly. Although high
      Metformin concentrations were found in gut biopsies, precise histological
      analysis in the isolated intestine revealed that it was absent from enterocytes;
      however the drug accumulated in villous lacteals. Intrarterially applied
      Metformin decreased glucose absorption in the isolated perfused ileo-jejunal
      segment. These data suggested that vascular Metformin boosted intestinal
      anaerobic glucose metabolism. Biochemical measurements performed on freshly
      isolated enterocytes showed that even high Metformin levels did not interfere
      with cell respiration or with Na+/K+ ATPase activity. Thus, our data agree with
      other recent reports, suggesting that even at nontherapeutic concentrations
      Metformin has no relevant inhibitory effect on intestinal glucose absorption. The
      data are discussed in the frame of previous divergent observations. The results
      suggest however that Metformin of vascular origin stimulates glucose consumption
      by the intestine, which then increases lactate output from the gut.

PMID- 7713277
TI  - Lower-extremity arterial disease in diabetes mellitus due to chronic
      pancreatitis.
AB  - OBJECTIVE: To determine the prevalence of lower-extremity arterial disease and
      the sites of arterial obstruction in patients with pancreatic diabetes. PATIENTS
      AND METHODS: The retrospective study included 83 patients with diabetes due to
      chronic pancreatitis (age [m +/- SD] 54.5 +/- 9.5 yr, diabetes duration 9.7 +/-
      7.4 yr) and 83 patients with idiopathic diabetes were carefully matched for sex,
      age, diabetes duration and treatment. They were screened for arteriopathy by
      segmental blood pressures and Doppler ultrasound, and for cardiovascular risk
      factors. The arterial lesions were classified as proximal (above-knee), distal
      (below-knee), and combined (both above- and below-knee). RESULTS: Lower extremity
      arterial disease occurred in 25.3% of pancreatitis patients and in 14.5% of
      idiopathic diabetes patients (p = 0.08). The sites of obstruction in both groups
      were similar; proximal obstruction: 4 vs 4 cases; distal: 10 vs 5 cases,
      combined: 7 vs 3 cases. The prevalence of arteriopathy increased with age and
      diabetes duration in both groups (p < 0.01). Total cholesterol, LDL cholesterol
      and apolipoprotein B were lower in the pancreatitis patients (p < 0.01); 92% of
      these were smokers vs 62% of idiopathic diabetes patients (p < 0.001).
      CONCLUSIONS: Arteriopathy, assessed by non-invasive tests, has the same
      prevalence and distribution in chronic pancreatitis and idiopathic diabetes
      patients, despite their different vascular risk factor profiles. This emphasizes
      the role of chronic hyperglycaemia and its duration in the pathogenesis of
      macroangiopathy in diabetic patients.

PMID- 7713278
TI  - Variability of blood glucose levels in patients with type 1 diabetes mellitus on
      intensified insulin regimens.
AB  - The aim of the present study was to look for possible associations between the
      blood glucose variability and twenty-four clinical parameters in ninety-eight
      patients with Type 1 diabetes mellitus treated with multiple injections of
      insulin or insulin pumps and practising self-monitoring of blood glucose. The
      blood glucose variability was measured as the standard deviation of glucose
      values obtained by self-monitoring at five specified time points every two days
      for four weeks. The blood glucose variability significantly correlated with the
      mean blood glucose level (r = 0.48, p = 0.0001) and with the number of
      hypoglycaemic events (r = 0.31, p = 0.002), but not with HbA1c (r = 0.19, p =
      0.07). Significant correlations were also found between glucose variability and
      patients' variations of insulin dosage (r = 0.31, p = 0.004), duration of
      diabetes (r = 0.22, p = 0.03), and body-mass index (r = 0.20, p = 0.04). Patients
      with incipient or clinical nephropathy had more variable blood glucose values,
      compared with patients without signs of nephropathy (p = 0.03). Other parameters
      studied, such as other late diabetic complications, the C-peptide level, the
      insulin dose and the level of insulin-binding to antibodies did not relate
      significantly to the blood glucose variability.

PMID- 7713279
TI  - [Intravenous glucose tolerance test in the functional exploration of segmental
      pancreatic autografts in the dog].
AB  - The aim of the present study is based on the comparison of intravenous tolerance
      testing before and after segmental pancreas autotransplantation in the dog. The
      results show that such testing must take in account the "glucose diffusion
      space", using the same glucose load in order to avoid the bias related to the
      post-operative loss of body weight.

PMID- 7713280
TI  - [How should insulin sensitivity be evaluated in practice?].

PMID- 7713281
TI  - Lack of in vitro complement activation by the human insulin analogue
      LYS(b28)PRO(B29)

PMID- 7713282
TI  - Geographical variation of type 1 diabetes mellitus and pancreatic carcinoma.

PMID- 7713283
TI  - QT prolongation in type 2 diabetes mellitus treated with glibenclamide.

PMID- 7713284
TI  - On the appropriate use of the primed-constant tracer infusion technique.

PMID- 7713285
TI  - The flush revisited.
AB  - A nadir of LH precedes the onset of the flush and a flush is never seen without
      an LH pulse. However, after surgical and medical (GnRH agonist) hypophysectomy
      flushing occurs while LH is absent, thus LH itself is not the cause of the flush.
      GnRH agonist treatment induces low LH, whereas flushes remain, even when
      oestrogens are supplemented, suggesting that GnRH itself is the mediator. As
      flushes are preceded by a spike of LH-RH, GnRH involvement is most likely.
      Pulsatile administration of GnRH does not induce flushes, whereas continuous
      administration does. Thus it is the interference with the pulsatile pattern of
      GnRH that causes flushes. Even high doses of oestradiol during GnRH agonist
      treatment do not abolish flushes, whereas the alpha 2-adrenergic agonists such as
      clonidine and alpha-methyldopa abolish flushes during treatment with GnRH
      agonists. Thus, dysregulation of the GnRH releasing clock center in the nucleus
      arcuatus in the mediobasal hypothalamus is associated with altered central alpha
      receptor activity which results in lowering of the set point of the central
      thermostat and the circulatory changes. The balance of evidence indicates that
      interference with the pulsatile pattern of GnRH causes the flush.

PMID- 7713286
TI  - The future of obstetrics and gynaecology in Europe.
AB  - There is a general recognition that the health of women in Europe can be improved
      by collaboration between obstetricians and gynaecologists in EU and EFTA
      countries. The way in which collaborative approaches are developing are
      discussed, including the problems that have to be addressed if such an initiative
      is to be successful.

PMID- 7713287
TI  - Increased levels of cytokines and cytokine activity modifiers in normal
      pregnancy.
AB  - Accumulating evidence suggests that cytokines are major participants in human
      reproduction. Cytokines may have beneficial or negative influence on pregnancy
      outcome, depending on the cytokine level present. Thus, successful reproduction
      appears to depend on a tight regulation of cytokine activities. The present study
      raised the question whether normal pregnancy is associated with an activation of
      native cytokine buffer mechanisms. Soluble interleukin 6 receptors (IL-6Rs) and
      soluble interleukin 1 receptor antagonists (IL-1RAs) may modify the activity of
      IL-6 and IL-1, respectively. The production of soluble IL-6R and IL-1RA in
      pregnancy was studied by assessing the IL-6R and IL-1RA concentrations in serum
      samples from healthy pregnant women at different gestational ages. At delivery,
      both maternal and umbilical blood was obtained. Concentrations of IL-6 and IL-1
      in the samples were determined to study the influence of cytokines on the
      activity level of the corresponding buffer mechanism. Serum levels of both IL-6R
      and IL-1RA were increased in pregnant women, as were levels of IL-6 and IL-1.
      Cytokine levels did not demonstrate a significant correlation with the
      concentration of the corresponding activity modifier. IL-1RA and IL-6 increased
      with gestational age and with labor activity. A significant correlation was
      observed between the levels of IL-6 and IL-1RA.

PMID- 7713288
TI  - Changes in cervical electromyographic activity and their correlation with the
      cervical response to myometrial activity during labour.
AB  - Intrauterine pressure, cervical dilatation and cervical electromyographic
      activity were recorded synchronously in five women from induction through the
      latent phase of labour and into the active phase. In all cases the
      electromyographic activity recorded in early labour was grouped into bursts
      synchronised with uterine and cervical contractions. Between these increases in
      electromyographic activity a significant background level of electrical activity
      was present in each case. With effacement the amount of electrical activity from
      the cervix was reduced, although increases in activity were noted to be
      synchronous with myometrial activity and, at this stage, dilatation of the
      cervix. This type of activity was typical of the active phase of labour until
      full dilatation, whilst the previous pattern typified the latent phase. The
      implications of these findings for the function of the cervix and the mechanism
      of cervical effacement are discussed.

PMID- 7713289
TI  - Primary carcinoma of fallopian tube: experience of six cases.
AB  - Between 1980 and 1993, six cases of primary carcinoma of the fallopian tube were
      diagnosed and treated at the Hospital of Rovigo. Median age was 64.6 years; the
      most frequent symptom was atypical vaginal bleeding; only one patient presented a
      history compatible with hydrops tubae profluens. No patient in this series had a
      correct preoperative diagnosis. In Papanicolau smears and endometrial currettage,
      one case was positive for cancer. Primary surgical treatment was performed in all
      cases, followed by adjuvant chemotherapy. Histologic differentiation was Grade 2
      in three patients and Grade 3 in three patients. Staging was by a system
      analogous to the FIGO classification for ovarian carcinoma. Two patients had
      Stage I disease; one, Stage II; two, Stage III; and one, Stage IV. Two patients
      died 14 and 37 months after the initial diagnosis. Three patients without
      clinical evidence of disease underwent second look procedures; the patients were
      alive and disease free with follow up ranging from 45 to 55 months. One patient
      is alive 4 months after surgery. In this series survival was not associated with
      grade, but was dependent upon stage. In our study, the prognostic value of the
      second- and third-look procedures are discussed.

PMID- 7713290
TI  - Risk factors for recurrence in clinically early endometrial carcinoma: an
      analysis of 183 consecutive cases.
AB  - This study includes 183 patients with clinical stage I endometrial carcinoma. All
      patients had standard surgical staging procedure including peritoneal cytology,
      total abdominal hysterectomy, bilateral pelvic and paraaortic lymphadenectomy.
      The factors analysed for recurrence were age, menopausal state, cell type, grade,
      mitotic activity, myometrial invasion, lymphovascular space invasion, cervical
      involvement, microscopic vaginal metastases, adnexal metastases, peritoneal
      cytology, concomitant endometrial hyperplasia and pelvic and paraaortic node
      metastases. The overall recurrence rate was 14.2% (26/183). Of the 26 patients
      with recurrence, 11 had local and 13 had distant metastases. In the remaining two
      patients (7.7%), both local and pelvic metastases were observed. Of the factors
      analysed, age, grade, mitotic activity, myometrial invasion, lymphovascular space
      invasion, microscopic vaginal metastases, adnexal involvement and pelvic and
      paraaortic nodal metastases were found to be significant predictors of
      recurrence. After multivariate analysis, advanced age (RR = 1.05), marked mitotic
      activity (RR = 3.11), pelvic and/or paraaortic nodal metastases (RR = 6.37) were
      chosen as the most important determinants of recurrence. In terms of surgical
      pathological stages, recurrence risk reaches up to 45.4% for stage IIIC disease.
      Using surgical pathological parameters, it is possible to predict recurrence but
      because of high rate of distant failures it still seems hard to improve survival
      of this group. Detection of a substantial risk of recurrence even in stage IA/B
      grade 1 group warrants adjuvant therapy in all patients after primary surgery.

PMID- 7713291
TI  - Post-abortion-hysteroscopy--a method for early diagnosis of congenital and
      acquired intrauterine causes of abortions.
AB  - OBJECTIVE: A prospective study was conducted on the incidence of intrauterine
      pathology diagnosed by hysteroscopy. STUDY DESIGN: A hysteroscopy was performed
      in 53 women 6-12 weeks after a dilatation and curettage for incomplete abortions
      or missed abortions. RESULTS: Uterus malformations were found in 11 patients,
      submucous myoma in two and a corpus polyp in one. The main findings were
      intrauterine adhesions in 16 cases. The incidence of intrauterine adhesions was
      about the same after incomplete abortions and after missed abortions, but in
      patients with recurrent abortions the incidence was significantly higher than in
      patients after first abortion (47.6% versus 18.8%). CONCLUSION: Post-abortion
      hysteroscopy is a simple and useful method for early diagnosis of acquired and
      congenital intrauterine pathology after abortions.

PMID- 7713293
TI  - Assessment of menstrual blood loss in women referred for endometrial ablation.
AB  - We measured menstrual blood loss in 54 women preferred for endometrial ablation
      on account of dysfunctional uterine bleeding. Patients' subjective assessment of
      blood loss was assessed by visual analogue scores and by pictorial blood loss
      assessment charts. The former were not related to measured blood loss but the
      charts were a useful test for menorrhagia, with 88% sensitivity, 52% specificity
      and a false positive rate of 59%.

PMID- 7713292
TI  - Serum tetranectin and CA-125 used to monitor the course of treatment in ovarian
      cancer patients.
AB  - Serum tetranectin (Se-TN) and CA-125 were measured in serum samples obtained
      before primary surgery, before start of chemotherapy and monthly during
      chemotherapy in 8 patients with ovarian cancer. The median Se-TN level before
      chemotherapy (7.3 mg/l) increased significantly after the start of chemotherapy
      (13.7 mg/l), with the highest increase for one survivor (145%). Five patients who
      died of cancer in the study period, had pronounced decreases (30-50%) in Se-TN
      with a maximal concentration during chemotherapy to the lowest concentration in
      the last sample. One patient who died 10 months after closure of the study had
      continuously normal Se-TN values, but the last CA-125 value elevated. The lead
      time could be calculated in four patients for Se-TN and six patients for CA-125.
      Median lead times of 3.6 months and 3.8 months were found for Se-TN and CA-125
      respectively. In conclusion, chemotherapy induces significant increases in Se-TN
      levels. A decrease in Se-TN during chemotherapy is highly suspect for recurrence
      and a poor outcome. Measurements of TN should therefore be included in other
      comparative studies.

PMID- 7713295
TI  - Intrauterine growth retardation and plasma fatty acids in the mother and the
      fetus.
AB  - BACKGROUND: Assessing the relationship between plasma fatty acids, specially
      polyunsaturated fatty acids in the mother and the fetus and intrauterine growth
      retardation (IUGR) in an apparently well-nourished population. DESIGN: Case
      control intrapartum analysis. SETTING: Academic tertiary hospital. PATIENTS,
      PARTICIPANTS: There were 17 IUGR newborn cases (23 mothers) and 34 newborn
      control cases (46 mothers). MAIN OUTCOME MEASURE: Eleven fatty acids were blindly
      analysed in plasma by means of gas chromatography. RESULTS: Percentage values of
      eicosapentaenoic acid among mothers from the IUGR group were significantly higher
      than controls, whereas stearic absolute values were significantly reduced. On the
      other hand there were no differences in percentage values nor in absolute values
      regarding the 11 fatty acids analysed in newborn infants. CONCLUSION: In an
      apparently well-nourished population IUGR is not associated with an alteration in
      plasma fatty acids on the fetal side. However, on the maternal side some
      imbalance in eicosapentaenoic and stearic acids were found which will require
      further study.

PMID- 7713294
TI  - Promotive effect by prostasomes on normal human spermatozoa exhibiting no forward
      motility due to buffer washings.
AB  - Prostasomes, small corpuscular organelles derived from the prostate gland, were
      isolated from human seminal plasma by means of ultracentrifugation and Sephadex G
      200 chromatography to assess objectively their promotive effect on the motility
      of buffer-washed normal human spermatozoa exhibiting no forward motility.
      Prostasomes were efficacious in about 70% of these spermatozoa, and a maximum
      value was obtained with prostasomes at a concentration corresponding to a protein
      content of 0.7-0.8 g/l followed by a plateau at higher concentrations. Addition
      of albumin alone resulted in a similar response although at a somewhat lower
      level and about 50% of the spermatozoa were rendered motile with a maximum effect
      of albumin at about 2.5 g/l. Albumin concentrations exceeding 3 g/l were less
      active. At protein concentrations of 0.25 g/l, prostasomes were superior to
      albumin in every respect concerning the effects on various sperm movement
      characteristics. These divergent effects were abolished when comparing
      prostasomes corresponding to a protein concentration of 0.75 g/l with albumin at
      2.3 g/l, i.e. at their respective optimum concentration. Heat treatment and
      ultrasonication of prostasomes did not affect their motility-promoting
      properties. Some problem of sperm dysfunction has generally been considered to be
      a major contributory factor to infertility. By supplementing sperm preparations
      with postasomes in cases of established male factor, the already poor quality
      spermatozoa may more frequently be rendered capable of fertilization after
      insemination.

PMID- 7713297
TI  - Laparoscopic removal of retained surgical gauze after vaginal hysterectomy.
AB  - Surgical gauze was retained intraabdominally in a woman who had undergone a
      vaginal hysterectomy with anterior colporrhaphy. Laparoscopic removal was
      successfully performed with minimal risk or trauma to the patient. The integrity
      of the vaginal vault support was maintained and the need for a laparotomy
      avoided. The use of laparoscopy in vaginal hysterectomy should be considered as
      this offers the chance to assess the pelvis pre- and post-operatively and to
      remove the ovaries, where indicated.

PMID- 7713298
TI  - Development of proliferative retinopathy in a gestational diabetes patient
      following rapid metabolic control.
AB  - Rapid glucose control was achieved by insulin therapy in a patient diagnosed to
      have gestational diabetes at 8 weeks of pregnancy. A decrease of the initially
      high hemoglobin A1c level (16.2%) to normal values (5.9%) was achieved within 12
      weeks. At 31 weeks severe bilateral proliferative diabetic retinopathy developed.
      To our knowledge this case is the first report of a patient with gestational
      diabetes who developed de novo proliferative diabetic retinopathy.

PMID- 7713296
TI  - Contraceptive use and attitudes in reunified Germany.
AB  - Contraceptive use and attitudes were assessed in a random sample of 1064 German
      women. The majority (76%) of the sexually active, fertile women who were not
      pregnant and did not wish to get pregnant at the time of the survey were using
      very reliable contraceptive methods, namely oral contraceptives (OCs),
      intrauterine devices (IUDs) or sterilization. Comparison with a previous survey
      showed that contraceptive practice in West Germany had improved considerably
      since 1985. Attitudes towards the most reliable methods available (OCs, IUDs and
      sterilization) were found to be ambivalent. Perceived side effects and health
      risks were a particular matter of concern to the respondents. Although most
      respondents (88%) recognized that condoms prevent the transmission of AIDS, 66%
      of those who had occasional sexual partners did not use barrier methods. It is
      concluded that German contraceptive practice is reasonably effective and that if
      attitudes were to become more realistic the level of effectiveness could even be
      raised.

PMID- 7713299
TI  - Conservative management of severe chronic hypertension in pregnancy.
AB  - Severe chronic hypertension in pregnancy is a condition frequently associated
      with poor maternal and fetal outcome. Meticulous antenatal care can lead to a
      reduction in morbidity and mortality. The case described is that of a
      primigravida who presented with severe chronic hypertension in the midtrimester
      of pregnancy. She was treated with four antihypertensive drugs and aspirin, and a
      favourable pregnancy outcome was achieved.

PMID- 7713300
TI  - XIV World Congress of Gynecology and Obstetrics (FIGO). Montreal, Canada,
      September 26-30, 1994. Abstracts.

PMID- 7713301
TI  - Breastfeeding as a women's issue: a dialogue on health, family planning, work and
      feminism. Washington, DC, September 13, 1993.

PMID- 7713302
TI  - Effects of breastfeeding on women's health.
AB  - Research about the effects of breastfeeding on maternal health has concentrated
      primarily on breast cancer, bone loss, and maternal depletion. Breastfeeding may
      provide some protection against breast cancer. Adequate maternal nutrition, a
      prolonged period of weaning, and adequate child spacing are expected to alleviate
      any potential bone loss or maternal depletion caused by breastfeeding. Regardless
      of how one chooses to weight the relative benefits and risks of breastfeeding to
      the mother, it seems clear that the programmatic tasks are to see that
      breastfeeding women are adequately fed and enabled to space their pregnancies.

PMID- 7713303
TI  - Breastfeeding in family planning programs: a help or a hindrance?
AB  - Breastfeeding is a major contributor to child spacing and reproductive health,
      and as such, is a vital women's issue. Further, if breastfeeding levels were to
      decline, the increase in family planning services that would be required to
      replace the lost fertility impact would be prohibitive, both in terms of cost and
      difficulty. This concern places breastfeeding centrally as a family planning
      policy issues as well. This paper discusses how breastfeeding contributes to
      child spacing and reduced fertility; the appropriate and timely introduction of
      complementary family planning methods during breastfeeding; issues and
      controversies in the support of breastfeeding as a family planning issue in the
      context of women's concerns, including the concept of exclusive breastfeeding for
      6 months, the encouragement and support to maintain breastfeeding after 6 months,
      and the use of the Lactational Amenorrhea Method (LAM) and other family planning
      methods in the early postpartum period; and the role of family planning programs
      in supporting women's informed reproductive health choices.

PMID- 7713304
TI  - The human reproductive pattern and the changes in women's roles.
AB  - A broader evolutionary perspective and an understanding of our reproductive
      behavior in the context of a constantly changing society can contribute to the
      debate on breastfeeding and reproductive roles of both women and men.
      Breastfeeding is women's work and should be valued as such. Families and
      societies need to accept their share of the task of supporting women to
      breastfeed, to include favorable conditions at the workplace, adequate health
      care, better nutrition, and recognition of the woman's role and importance.

PMID- 7713305
TI  - Every mother is a working mother: breastfeeding and women's work.
AB  - Working and breastfeeding can be very complicated because of the kinds of work
      women are doing; the settings in which they are working; recent changes which
      have made breastfeeding and work less compatible; trade-offs that working mothers
      must make; the importance of breastfeeding for the working woman; and the range
      of feeding options for working mothers. To adequately address these and other
      issues, several initiatives are needed: (1) additional research on breast pumping
      and breastmilk storage, and the social and emotional benefits of breastfeeding
      for working mothers and their infants; (2) protective legislation and strategies
      for its implementation and monitoring; (3) information and support for
      breastfeeding mothers and families, policy markers, and the general public; and
      (4) an alliance between breastfeeding advocates and feminists to promote this
      intrinsically female issue.

PMID- 7713306
TI  - Breastfeeding and feminism.
AB  - Breastfeeding empowers women and contributes to gender equality; therefore, it is
      an important feminist, human rights, and women's issue. Although seldom addressed
      as a feminist issue, breastfeeding is paradigmatically one because it requires
      rethinking basic issues such as the sexual division of labor, the fit between
      women's productive and reproductive lives, and the role of physiological
      processes in defining gender ideology. The conceptual problems which emerge in
      the fit between breastfeeding promotion and feminist theory include the place of
      motherhood; technology versus liberation; fear of biological determinism; breasts
      and sexuality; locating guilt; personal choice; romanticizing breastfeeding; and
      conceptualizing women's work. Feminist theorists who take up breastfeeding as an
      issue and medical researchers who address questions raised by feminist theory
      have the occasion to produce a non-dualistic feminist problematic that would draw
      together a wide range of theories and practices that go beyond breastfeeding and
      mothering. The failure to develop this analysis could have serious consequences.

PMID- 7713307
TI  - Breastfeeding as a women's issue: conclusions and consensus, complementary
      concerns, and next actions.
AB  - Twelve themes arose during the conference which, when presented to the group in a
      summary session, were greeted by general consensus and approval. These themes
      fall into four categories: women and health care; women and other life choices;
      women and men; and women and political action. Additional concerns that were not
      included in the 1-day conference are outlined, including a discussion of: (1)
      respect for the reproductive roles of women, the three 'I's', and other
      reproductive health issues; (2) a 7-stage approach to women's nutrition; (3) the
      supervisory role of the health care provider versus a role as a creator of self
      efficacy; (4) the cost of breastfeeding; and (5) the impact on the environment.
      Conclusions and next actions also are presented for consideration.

PMID- 7713309
TI  - Adoptive transfer of diabetes to and from old normoglycaemic BB rats.
AB  - Approximately 4% of diabetes-prone BB/Mol rats escape overt diabetes which occurs
      in other rats between 56 and 130 days of age. The ability of preactivated spleen
      cells from older non-diabetic and from acutely diabetic rats to adoptively
      transfer diabetes into young diabetes-prone rats was compared, and it was found
      that they transferred disease with similar incidence and with overlapping onset
      times in the recipients. Old non-diabetic rats were themselves susceptible to
      diabetes adoptively transferred from acutely diabetic or from old nondiabetic
      donors. Lymphocytic insulitis and pancreatic insulin content in unmanipulated old
      non-diabetic rats were both intermediate between those seen in acutely diabetic
      and in diabetes-resistant rats. In vivo treatment with polyinosinic-polycytidylic
      acid induced diabetes with faster onset in old non-diabetic rats than in young
      diabetes-prone rats. Adoptive transfer of fresh, whole spleen cells from old
      nondiabetic rats did not protect young BB rats against spontaneous diabetes,
      while cells from diabetes-resistant rats did. Spleens from old non-diabetic rats
      contained significantly lower percentages of T cells than spleens from acutely
      diabetic rats but not lower than spleens from age-matched diabetic rats,
      suggesting that this reduction was age-related. Finally, spleens from both old
      non-diabetic and from acutely diabetic rats were negative for the regulatory RT6+
      T-cell subset. It is concluded that quiescent beta-cell autoimmunity seen in a
      fraction of BB/Mol rats can be reactivated upon non-antigen-specific immune
      stimulation.

PMID- 7713308
TI  - Effects of anti-oxidant treatment on sciatic nerve dysfunction in streptozotocin
      diabetic rats; comparison with essential fatty acids.
AB  - In Study 1, the effects of treatment of streptozotocin-diabetic rats with the
      antioxidants, probucol or vitamin E were compared. Untreated diabetic rats showed
      a reduction of 45% (p < 0.01) in nerve laser Doppler flux, which was used as an
      index of nerve blood flow. In diabetic rats treated with either probucol or
      vitamin E nerve Doppler flux was reduced by only 13 or 16%, respectively (p <
      0.01 for either compared to untreated diabetic rats). A second study examined the
      effects of treatment with evening primrose oil either alone or in combination
      with probucol. Reduced nerve Doppler flux was reproduced in untreated diabetic
      rats (47%; p < 0.01). In parallel diabetic groups, nerve Doppler flux was reduced
      by only 14% with evening primrose oil alone and by 8% with evening primrose oil
      plus probucol (both p < 0.01 vs untreated diabetic rats). Both treatments were
      also associated with marked attenuation of motor and sensory nerve conduction
      velocity deficits. Measurements on plasma from rats showed normalisation of
      triglyceride levels by probucol treatment without an effect on those of
      cholesterol in Study 1. In Study 2, the converse was true for evening primrose
      oil treatment, whilst the combined treatment lowered both plasma triglycerides
      and cholesterol. This work indicates similar effects of antioxidants and evening
      primrose oil against reduced nerve Doppler flux and conduction velocity in
      diabetic rats, with dissimilar actions on plasma triglycerides and cholesterol.

PMID- 7713312
TI  - Biological effects of encapsulated insulin on transfected Chinese hamster ovary
      cells.
AB  - Oral administration of insulin incorporated into the wall of
      isobutylcyanoacrylate nanocapsule to diabetic rats induces a long-lasting
      normalization of their fasting glycaemia. In this study, we examined the
      biological action of encapsulated insulin on DNA and glycogen syntheses in
      Chinese hamster ovary cells transfected with the human insulin receptor gene. In
      the 10(-11) mol/l-10(-9) mol/l concentration range, encapsulated insulin elicited
      responses comparable to those induced by native insulin: at 10(-9) mol/l, the
      rates of glycogen and DNA synthesis were enhanced by factors 3 and 2.5,
      respectively. Encapsulated insulin at 10(-7) mol/l evoked receptor
      desensitization although it did not induce receptor down-regulation and did not
      alter receptor recycling for up to 6 h. Chloroquine decreased the action of
      native insulin on glycogen synthesis, but did not affect the dose-response
      characteristics of encapsulated insulin. Acid-washing of the cells after 1 h of
      stimulation decreased maximal insulin responsiveness and provoked a dose response
      curve for encapsulated insulin similar to that of the native hormone. Direct
      measurement of effective insulin binding activity showed that encapsulated
      insulin (at 10(-8) and 10(-7) mol/l) was withdrawn from the incubation medium 5-8
      times less efficiently than native insulin. These data are in agreement with
      previous results showing that the polymeric wall protects encapsulated insulin
      from degradation. Persistence of intact encapsulated insulin inside and outside
      the cell may result in modifying signalling events and thus be responsible for
      the observed cellular desensitization.

PMID- 7713311
TI  - Caloric restriction in obese pre-diabetic rats prevents beta-cell depletion, loss
      of beta-cell GLUT 2 and glucose incompetence.
AB  - Pre-diabetic male Zucker diabetic fatty rats (ZDF) become diabetic between 8 and
      10 weeks of age. At that time their beta cells exhibit high basal insulin
      secretion, absent insulin response to glucose and loss of GLUT 2 glucose
      transporter. Beta-cell volume, which is increased at the onset of non-insulin
      dependent diabetes, declines precipitously by age 18 weeks. To determine if
      expression of this diabetic phenotype was dependent upon the increased food
      intake of these rats, they were diet-matched to lean littermates for 12 weeks
      beginning at 6 weeks of age. Untreated control ZDF rats received an unrestricted
      diet for 3 months. All of the controls became hyperglycaemic by 8 weeks of age,
      whereas all diet-matched rats remained euglycaemic throughout the 3 months,
      despite the fact that at 18 weeks of age their mean body weight equaled that of
      obese rats on an unrestricted diet. In the former rats glucose-stimulated insulin
      secretion was absent at 12 weeks of age and GLUT-2-positive beta cells had fallen
      below 30%. The volume fraction of their beta cells was 2.6 times normal at this
      age but by 18 weeks of age it had declined by 75%. Diet restriction for 3 months
      prevented the loss of glucose-stimulated insulin secretion and the reduction of
      beta-cell GLUT-2 and beta-cell volume fraction. However, neither the elevated
      basal insulin secretion nor the exaggerated arginine-stimulated insulin secretion
      of the obese rats was reversed or prevented by caloric restriction.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7713313
TI  - Early and late insulin response as predictors of NIDDM in Pima Indians with
      impaired glucose tolerance.
AB  - Risk factors predicting deterioration to diabetes mellitus were examined in 181
      subjects with impaired glucose tolerance. Fifty-seven subjects had impaired
      glucose tolerance on one occasion followed by normal glucose tolerance at a
      repeat oral glucose tolerance test, and 124 subjects had impaired glucose
      tolerance on two successive oral glucose tolerance tests. Subjects were followed
      for a median period of 5.0 years (range 1.0-17.2). The age- and sex-adjusted
      cumulative incidence of diabetes at 10 years of follow-up was higher in subjects
      who had impaired glucose tolerance on both tests (70%) than in those whose
      glucose tolerance was normal at the repeat test (53%), [rate ratio (RR) = 1.6,
      95% confidence intervals (CI) = 1.0-2.5]. Proportional hazards analyses were used
      to identify baseline risk factors (measured at the repeat oral glucose tolerance
      test) for subsequent diabetes, and incidence rate ratios were calculated for the
      90th percentile compared with the 10th percentile of each continuous variable for
      the whole group. In all subjects, in separate models, higher body mass index [RR
      = 2.0, 95% CI = 2.2-9.9], high fasting serum insulin concentrations [RR = 2.4,
      95% CI = 1.4-4.2], and low early insulin response [RR = 0.5, 95% CI = 0.3-0.8] 30
      min after a glucose load were significant predictors for deterioration to
      diabetes. In a multivariate analysis which controlled for age and sex, 120-min
      post-load glucose, fasting insulin and late insulin response predicted
      diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713310
TI  - Selective proteinuria in diabetic nephropathy in the rat is associated with a
      relative decrease in glomerular basement membrane heparan sulphate.
AB  - In the present study we investigated whether glomerular hyperfiltration and
      albuminuria in streptozotocin-induced diabetic nephropathy in male Wistar-Munich
      rats are associated with changes in the heparan sulphate content of the
      glomerular basement membrane. Rats with a diabetes mellitus duration of 8 months,
      treated with low doses of insulin, showed a significant increase in glomerular
      filtration rate (p < 0.01) and effective renal plasma flow (p < 0.05), without
      alterations in filtration fraction or mean arterial blood pressure. Diabetic rats
      developed progressive albuminuria (at 7 months, diabetic rats (D): 42 +/- 13 vs
      control rats (C): 0.5 +/- 0.2 mg/24 h, p < 0.002) and a decrease of the
      selectivity index (clearance IgG/clearance albumin) of the proteinuria (at 7
      months, D: 0.20 +/- 0.04 vs C: 0.39 +/- 0.17, p < 0.05), suggesting loss of
      glomerular basement membrane charge. Light- and electron microscopy demonstrated
      a moderate increase of mesangial matrix and thickening of the glomerular basement
      membrane in the diabetic rats. Immunohistochemically an increase of laminin,
      collagen III and IV staining was observed in the mesangium and in the glomerular
      basement membrane, without alterations in glomerular basement membrane staining
      of heparan sulphate proteoglycan core protein or heparan sulphate. Glomerular
      basement membrane heparan sulphate content, quantitated in individual glomerular
      extracts by a new inhibition ELISA using a specific anti-glomerular basement
      membrane heparan sulphate monoclonal antibody (JM403), was not altered (median
      (range) D: 314 (152-941) vs C: 262 (244-467) ng heparan sulphate/mg glomerulus).
      However, the amount of glomerular 4-hydroxyproline, as a measure for collagen
      content, was significantly increased (D: 1665 (712-2014) vs C: 672 (515-1208)
      ng/mg glomerulus, p < 0.01). Consequently, a significant decrease of the heparan
      sulphate/4-hydroxyproline ratio (D: 0.21 (0.14-1.16) vs C: 0.39 (0.30-0.47), p <
      0.05) was found. In summary, we demonstrate that in streptozotocin-diabetic rats
      glomerular hyperfiltration and a progressive, selective proteinuria are
      associated with a relative decrease of glomerular basement membrane heparan
      sulphate. Functionally, a diminished heparan sulphate-associated charge density
      within the glomerular basement membrane might explain the selective proteinuria
      in the diabetic rats.

PMID- 7713315
TI  - Weakened cellular scavenging activity against oxidative stress in diabetes
      mellitus: regulation of glutathione synthesis and efflux.
AB  - Glutathione functions to scavenge oxidants or xenobiotics by covalently binding
      them and transporting the resulting metabolites through an adenosine 5'
      triphosphate-dependent transport system. It has been reported that the
      intracellular concentration of glutathione decreases in diabetes mellitus. In
      order to elucidate the physiological significance and the regulation of anti
      oxidants in diabetic patients, changes in the activity of the glutathione
      synthesizing enzyme, gamma-glutamylcysteine synthetase, and transport of thiol [S
      (2,4-dinitrophenyl)glutathione] were studied in erythrocytes from patients with
      non-insulin-dependent diabetes and K562 cells cultured with 27 mmol/l glucose for
      7 days. The activity of gamma-glutamylcysteine synthetase, the concentration of
      glutathione, and the thiol transport were 77%, 77% and 69%, respectively in
      erythrocytes from diabetic patients compared to normal control subjects.
      Treatment of patients with an antidiabetic agent for 6 months resulted in the
      restoration of gamma-glutamylcysteine synthetase activity, the concentration of
      glutathione, and the thiol transport. A similar impairment of glutathione
      metabolism was observed in K562 cells with high glucose levels. The cytotoxicity
      by a xenobiotic (1-chloro-2,4-dinitrobenzene) was higher in K562 cells with high
      glucose than in control subjects (50% of inhibitory concentration 300 +/- 24
      mumol/l vs 840 +/- 29 mumol/l, p < 0.01). Expression of gamma-glutamylcysteine
      synthetase protein was augmented in K562 cells with high glucose, while enzymatic
      activity and expression of mRNA were lower than those in the control subjects.
      These results suggest that inactivation of glutathione synthesis and thiol
      transport in diabetic patients increases the sensitivity of the cells to
      oxidative stresses, and these changes may lead to the development of some
      complications in diabetes mellitus.

PMID- 7713314
TI  - Diabetes mellitus carrying a mutation in the mitochondrial tRNA(Leu(UUR)) gene.
AB  - We screened 214 Japanese NIDDM (non-insulin-dependent) diabetic patients with a
      family history of diabetes for mutations in the mitochondrial tRNA(Leu(UUR)) gene
      using polymerase chain reaction-restriction fragment length polymorphism and
      direct sequencing. Six patients were identified as having an A to G transition at
      position 3243 (3243 mutation), but no patients were detected with a T to C
      transition at position 3271, in the mitochondrial tRNA(Leu(UUR)) gene. These two
      mutations were not present in 85 healthy control subjects. It was disclosed that
      the patients' mothers were also affected by diabetes mellitus in five of the six
      cases. In these six affected patients, the 3243 mutation shows variable
      phenotypes, such as the degree of multiple organ involvement, intrafamilial and
      interfamilial differences in disease characteristics, and the degree of the
      involvement of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis,
      and stroke-like episodes) phenotype. Endocrinological examinations revealed that
      those diabetic patients with the 3243 mutation show not only beta-cell
      dysfunction, but also a defect in alpha-cell function, which is considered
      characteristic of diabetes with the 3243 mutation. When compared with 50 selected
      diabetic control subjects without the 3243 mutation, whose mothers, but not
      fathers, were found to have diabetes, it was established statistically that those
      with the 3243 mutation possess the following clinical characteristics; 1) the age
      of diabetes onset is lower, 2) they have lean body constitutions, and 3) they are
      more likely to be treated with insulin than control subjects. We suggest that
      diabetes with the 3243 mutation possesses phenotypes distinct from those in
      common forms of diabetes.

PMID- 7713316
TI  - Identification of two novel amino acid polymorphisms in beta-cell/liver (GLUT2)
      glucose transporter in Japanese subjects.
AB  - The beta-cell/liver glucose transporter (GLUT2) gene was screened for mutations
      using single-strand conformation polymorphism analysis (SSCP) in 30 Japanese
      subjects with non-insulin dependent diabetes mellitus (NIDDM). Analysis of all
      exons and adjacent intron regions identified six SSCP polymorphisms, three of
      which resulted in amino acid substitutions: V101I, T110I and G519E. The V101I and
      G519E, substitutions represent new polymorphisms in this gene. The six
      polymorphisms were observed in both NIDDM and control groups and there were no
      significant differences in allele frequencies between groups. A portion of the
      insulin receptor substrate 1 gene in 30 NIDDM subjects and in normal control
      subjects was also screened for mutations. Two SSCP variants that change the
      sequence of the protein, delta S686/687 (deletion of the codons for serine-686
      and 687) and G972R, were identified in two different NIDDM subjects, both whom
      were also heterozygous for the V101I polymorphisms in GLUT2. The GLUT2 and IRS1
      amino acid polymorphisms did not show a simple pattern of co-inheritance with
      NIDDM in the families of these subjects suggesting that neither polymorphism is
      sufficient to cause NIDDM but may increase diabetes-susceptibility through their
      interaction with other loci and environmental factors.

PMID- 7713318
TI  - Diabetic nephropathy: a risk factor for diabetes mellitus in offspring.
AB  - Both non-insulin-dependent diabetes mellitus and diabetic nephropathy show
      familial aggregation. If diabetes and renal disease have independent determinants
      (genetic or otherwise), offspring of parents with diabetic renal disease should
      have a similar risk of diabetes to those offspring of parents with diabetes
      alone. To test this hypothesis, the prevalence of diabetes was examined in a
      population-based pedigree study in Pima Indian offspring of three mutually
      exclusive parental types: 1) diabetic with renal disease, 2) diabetic, but
      without renal disease and 3) non-diabetic. Among offspring of one diabetic parent
      and one non-diabetic parent (n = 320) the prevalence of diabetes at ages 15-24
      years and 25-34 years was 0% and 11%, respectively if the diabetic parent did not
      have renal disease compared with 6% and 28% respectively if the diabetic parent
      did have renal disease. Corresponding rates for offspring of two diabetic parents
      (n = 121) were 10% and 17%, respectively if neither parent had renal disease
      compared with 30% and 50%, respectively if one parent did have renal disease. The
      presence of renal disease in a parent with diabetes relative to diabetes alone
      was associated with 2.5 times the odds of diabetes (95% confidence interval 1.4
      4.3) in the offspring controlled for age, age at onset of parental diabetes and
      diabetes in the other parent using logistic regression. These findings provide
      support for parental diabetic renal disease, independent of age at onset of
      parental diabetes, conferring an increased risk for diabetes in the
      offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713317
TI  - Latent overhydration and nocturnal hypertension in diabetic nephropathy.
AB  - With the aim of studying the diurnal variation in blood pressure in relation to
      degree of fluid retention, 24-h ambulatory blood pressure monitoring was
      performed in 31 insulin-dependent diabetic patients with nephropathy. The
      extracellular volume was calculated from the distribution volume of 51Cr-EDTA
      after a single injection. The study population was arbitrarily divided into two
      groups, depending on their extracellular volume. Group 1 included 15 patients
      with a lower extracellular volume and group 2, 16 patients with a higher
      extracellular volume. Ambulatory blood pressure was measured with a portable
      monitor using an oscillometric technique. In all patients, the mean +/- SD 24-h
      ambulatory blood pressure was 135/79 +/- 14/7 mmHg. Day and night-time blood
      pressure were 136/81 +/- 14/7 and 133/75 +/- 17/8, respectively (p < 0.02). The
      ambulatory blood pressure was 135/80 +/- 14/7 in group 1 and 136/78 +/- 15/6 mmHg
      in group 2. The nocturnal change in blood pressure was significantly greater in
      group 1 than in group 2, -9/-9 +/- 10/5 mmHg and 1/-3 +/- 10/6 mmHg, respectively
      (p = 0.005/0.01). There were no other significant differences between the groups
      than the diurnal blood pressure pattern. There were significant correlations
      between day ambulatory blood pressure and night ambulatory blood pressure and 24
      h ambulatory blood pressure and urinary albumin excretion. There was no
      correlation between ausculatatory clinic blood pressure on the one hand and
      albuminuria on the other. Latent fluid retention therefore may contribute to
      nocturnal hypertension in diabetic nephropathy.

PMID- 7713319
TI  - Pregnancies in women with diabetic nephropathy: long-term outcome for mother and
      child.
AB  - In order to improve the basis upon which to advise women with diabetic
      nephropathy about pregnancy, we studied the effect of diabetic nephropathy on the
      course of pregnancy, perinatal outcome, infant development and long-term outcome
      of the mothers. All pregnancies of women with diabetic nephropathy (defined as
      proteinuria > 400 mg/day (n = 26), creatinine clearance < 80 ml/min and
      hypertension in the first trimester (n = 10)) followed at our centre from 1982 to
      1992 were identified (34 White class F and 2 White class T) and the women and
      their children re-examined in the spring 1993. From the first to the third
      trimester the percentage of women with proteinuria over 3 g/day increased from 14
      to 53% and those treated with antihypertensive medication from 53 to 97%. There
      were no intrauterine or perinatal deaths, but one child died suddenly 4 weeks
      postpartum. Of 36 newborns (gestational week at birth 36(3), birth weight
      2384(834) g)), 11 were born before week 34 and 8 had respiratory distress
      syndrome. Renal function in the first trimester, diastolic blood pressure in the
      third trimester and an HbA1c above normal were predictive of gestational age at
      delivery and low birth weight (stepwise regression analysis). At follow up of the
      children (n = 35, age 4.5 (0.4-10) years) the majority (n = 27) were normally
      developed but seven had psychomotor retardation (four of them major). One child
      had a severe motor retardation due to a congenital anomaly. At follow up, 21 of
      the 29 mothers had preserved renal function (creatinine 1.3 (0.8-4.3) mg/dl and 8
      had developed end stage renal disease and required dialysis (2 of whom were White
      class T) within 3 (1-9) years postpartum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713320
TI  - Markedly increased renal disease mortality and incidence of renal replacement
      therapy among IDDM patients in Japan in contrast to Allegheny County,
      Pennsylvania, USA. Diabetes Epidemiology Research International (DERI) U.S.-Japan
      Mortality Study Group.
AB  - The aim of this study was to evaluate factors related to the markedly increased
      risk of dying from diabetic renal disease in Japanese insulin-dependent diabetic
      patients compared to those in the USA. The study was based on two population
      based cohorts consisting of 1374 cases from Japan and 995 cases from Allegheny
      County, Pennsylvania, USA, who were diagnosed between 1 January 1965 and 31
      December 1979. The living status and dialysis experience were determined as of 1
      January 1990. The duration-adjusted renal-failure-related mortality rates in the
      Japanese cohort and the USA cohort were 277.2 and 130.9 per 100,000 person-years,
      and the duration-adjusted incidence rates of dialysis were 564.9 and 295.6 per
      100,000 person-year, respectively. After adjustment for sex, age at onset,
      calendar year of onset, and duration of diabetes, individuals with insulin
      dependent diabetes in the Japanese cohort were still 2.4-fold more likely to
      receive dialysis compared to those in the USA cohort. Ten of the 36 renal-failure
      related deaths in the Japanese cohort had never been treated by dialysis, while
      all renal-failure-related deaths in the USA cohort had been treated by dialysis.
      Survival after initiation of dialysis in the Japanese cohort was virtually the
      same as the USA cohort. These data suggest that a greater frequency of diabetic
      end-stage renal disease and reduced access to acceptance at dialysis underlie
      much of the excess of diabetic renal deaths in Japan.

PMID- 7713322
TI  - Cerebral function in a relatively young subset of NIDDM patients.

PMID- 7713323
TI  - Monitoring kidney function in diabetic nephropathy.

PMID- 7713321
TI  - Cardiovascular response to exercise in diabetic patients: influence of autonomic
      neuropathy of different severity.
AB  - We investigated cardiovascular function and plasma catecholamine response during
      incremental exercise and recovery in diabetic patients with (DAN+) and without
      autonomic neuropathy (DAN-). The former group was divided according to the
      presence of parasympathetic (DAN+PH-) or associated parasympathetic and
      sympathetic (DAN+PH+) damage to the autonomic nervous system. A group of healthy
      volunteers was studied as a control group. All the patients and control subjects
      underwent a submaximal or symptom-limited incremental exercise test using a cycle
      ergometer. Air flow and respiratory gas fractions were sampled at the level of
      the mouth allowing a breath-by-breath analysis of oxygen consumption (VO2). Heart
      rate and systolic blood pressure were recorded and venous blood samples were
      obtained from the patients at rest and during each minute of exercise and
      recovery to measure norepinephrine and epinephrine plasma levels. Haemodynamic
      parameters and plasma catecholamines were computed at rest and at 25, 50, 75 and
      100% of the peak VO2 (VO2max). The breath-by-breath relationships among VO2,
      heart rate and VO2/heart rate against work were assessed during exercise for
      patients and control subjects. While VO2max in absolute values was not
      significantly different among the diabetic groups, VO2 max was much less in
      diabetic patients than in control subjects (p < 0.01). During exercise the rate
      of heart rate, systolic blood pressure, norepinephrine and epinephrine increase
      was different among the diabetic groups, being significantly blunted in DAN+PH+.
      The VO2/work relationship of the three diabetic groups was similar but markedly
      reduced in respect to that of control subjects (p < 0.001).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7713324
TI  - Plasma endothelin-1 immunoreactivity is increased following long-term dietary
      supplementation with omega-3 fatty acids in microalbuminuric IDDM patients.

PMID- 7713325
TI  - Protein kinase A is a positive regulator of spore coat gene transcription in
      Dictyostelium.
AB  - The cotA, cotB, and cotC genes encode the major spore coat proteins of
      Dictyostelium. All three cot genes are coordinately expressed as aggregation is
      nearing completion. Induction and maintenance of their expression is dependent
      upon the presence of extracellular cAMP. We show that expression of a dominant
      inhibitor of the cAMP dependent protein kinase (PKA) in prespore cells greatly
      reduces the transcription rates of the cotB and cotC genes. All three cot genes
      contain, in their upstream regulatory regions, short sequence elements that have
      a high content of cytosine and adenosine residues. These CA-rich sequences are
      essential for optimal cot gene transcription. We show that expression of the
      dominant PKA inhibitor results in a greatly reduced level of the binding activity
      that recognizes the CA-rich sequences upstream of the cotB gene. Thus PKA acts,
      either directly or indirectly, to control expression of the cot genes and it may
      do so by modulating the activity of a DNA binding protein. However, we find that
      mutant cells where PKA is constitutively active still require exogenous cAMP for
      optimal cot gene expression in dissociated cells, suggesting that a separate, PKA
      independent, signalling pathway is also involved in the regulation of cot gene
      expression by extracellular cAMP.

PMID- 7713326
TI  - Cell birthdays in Xenopus laevis retina.
AB  - Using an in vitro differentiation system, we reevaluated the stages of
      development during which retinal neurons become postmitotic in Xenopus laevis. We
      also examined whether retinal detachment and removal of the pigment epithelium
      stimulated proliferation of previously postmitotic retinal cells. Retinas with
      and without an adherent pigment epithelium (stages 24-40 and stage 33/34,
      respectively) were removed from X. laevis embryos, placed in culture and allowed
      to differentiate in the presence of 3H-thymidine. After 2 days, eyes were fixed
      and processed for autoradiography. The proportion of labeled to unlabeled nuclei
      in the posterior pole of the retina was determined for each of the three cell
      layers. Early in development, most unlabeled cells were found in the ganglion
      cell layer; at stage 24, 53% of the cells showed no labeling, but by stage 32
      33/34 all of the cells present were unlabeled. Within the outer nuclear layer,
      17% of the cells failed to incorporate the 3H-thymidine at stage 24 and by stage
      33/34, 100% of the cells were unlabeled. Within the inner nuclear layer, 13.5% of
      the cells failed to show labeling at stage 24, whereas at stage 40, none of the
      cells were labeled. There was no difference in the proportion of labeled to
      unlabeled nuclei in any of the cell layers when retinas were allowed to
      differentiate either with or without an adherent pigment epithelium. These
      results indicate that as early as stage 24, some cells that will become
      positioned in each of the nuclear strata fail to incorporate 3H-thymidine,
      suggesting that these cells become postmitotic very early in
      neurogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713327
TI  - The inhibition of cell proliferation by mitomycin C does not prevent
      transdifferentiation of outer cornea into lens in larval Xenopus laevis.
AB  - The aim of the present work is to evaluate the relationship between cell
      proliferation and transdifferentiation (TS) of the outer cornea into lens in
      larval Xenopus laevis. Data obtained from corneal fragments treated with
      Mitomycin C (MMC) (0.1 mg/ml, 50 min) and implanted into the vitreous chamber
      (MMC/v ch) were compared with those obtained from untreated corneal fragments
      implanted into the vitreous chamber (contr/v ch) or between outer and inner
      corneas (contr/o c). Results demonstrated that in contr/v ch implants, which
      transdifferentiated into lenses or lentoid bodies in 88% of cases, the mitotic
      index (MI) showed a sharp increase during the period of lens vesicle formation (3
      days) and became very low when the formation of lens fibres was under way (7
      days). In contro c implants, which did not undergo any lens forming
      transformations, the MI remained unchanged in comparison to time O. In MMC/v ch
      implants, the inhibition of the mitotic activity was 100% up to the third day
      after implantation. On the fifth and seventh days, scant mitotic activity was
      observed in some cases, but the MI was much lower than the MI of contr/o c
      implants. The MMC/v ch implants transdifferentiated into lentoid bodies in 26% of
      cases. The lentoid bodies were much smaller than those observed in control
      implants, but they reacted positively with the lens antibodies at the same time
      after implantation as controls. Even the complete inhibition of proliferation due
      to stronger MMC treatments (e.g. 0.15 mg/ml, 50 min) did not prevent lens
      TS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713328
TI  - The polarity of the membrane skeleton in retinal pigment epithelial cells of
      developing chicken embryos and in primary culture.
AB  - We studied the morphogenesis and the membrane skeleton in the retinal pigment
      epithelium during chicken embryogenesis and in culture, by using
      immunofluorescence and electron microscopy. During embryogenesis two distinct
      membrane skeletal structures were formed, an apical and a basolateral one. The
      former was seen in the apical surface already in the 10-day-old embryos. It was
      comprised of ankyrin and alpha-fodrin and showed a codistribution with Na+,K(+)
      ATPase and an as yet uncharacterized cadherin-like molecule. The basolateral
      membrane skeleton was seen in the lateral walls already in the 10-day-old
      embryos, and later, between the 13th and 17th embryonic days, it also appeared at
      the basal membrane, coincidentally with the formation of the basal infoldings. It
      consisted of ankyrin and alpha-fodrin, but did not codistribute with any of the
      integral membrane proteins studied (Na+,K(+)-ATPase and cadherins). In culture,
      the retinal pigment epithelial cells retained their polarized morphology.
      Compared with the situation in vivo, however, there was a distinct translocation
      of the membrane skeletal components fodrin and ankyrin from the apical surface to
      the lateral walls, accompanied by a similar redistribution of Na+,K(+)-ATPase and
      the cadherin-like molecule. The results suggest that (1) there is, in the retinal
      pigment epithelium, an apical Na+,K(+)-ATPase-membrane skeleton structure
      stabilized by contacts between the retinal pigment epithelium and the neural
      retina, possibly mediated by a cadherin-like molecule, and that (2) there is
      another fodrin/ankyrin-based membrane skeleton in the basolateral walls that is
      important for the maintenance of the extensive folding of these surface areas.

PMID- 7713329
TI  - Alterations in gene expression associated with changes in the state of
      endothelial differentiation.
AB  - The endothelium maintains a developmental plasticity which allows rapid
      phenotypic change in response to extracellular signals during normal processes,
      such as corpus luteum formation and wound healing, and in pathologic processes,
      such as tumor angiogenesis. Endothelial cells (EC) in culture have been very
      useful for investigating various aspects of endothelial growth and behavior. In
      spite of documented similarities between EC in vitro and the endothelium in vivo,
      many characteristics of the vessel endothelium are lost when the cells are placed
      into culture. We have undertaken to identify differences in gene expression
      between differentiated vessel endothelium and dedifferentiated EC. We utilized a
      new technique called differential display which compares polymerase chain
      reaction (PCR)-amplified mRNA from two (or more) cell populations. Endothelium
      scraped directly from freshly obtained aortas, and demonstrated to be free of
      contaminants, were used as the source of differentiated RNA, whereas
      proliferating, primary explanted EC grown for five days in the presence of basic
      fibroblast growth factor (bFGF) provided a pool of 'dedifferentiated' RNA. Using
      differential display, we have observed numerous reproducible differences in gene
      expression. To confirm that the expression differences visualized by differential
      display represented actual differences in gene expression, we isolated vessel
      specific and culture-specific cDNA tags for additional analysis. Three cDNA tags
      specific to vessel endothelium were cloned and sequenced, and compared to
      nucleotide and protein databases. Two of the clones (A1 and 2.5) displayed no
      significant sequence similarity, whereas a third clone (A2) is nearly identical
      to a human expressed sequence tag (EST) and has significant sequence similarities
      to a plant and Xenopus ubiquitin-like protein. Northern and/or in situ
      hybridization analysis of the A1 and A2 genes confirmed their restricted
      expression to the vessel endothelium. The expression of A1 by the endothelium in
      vivo is not simply a function of growth state, as cultured cells did not express
      A1 even when grown to postconfluence. One other cDNA fragment, selected as a
      culture-induced gene, was identified by sequence analysis as the bovine homologue
      of laminin B1, and Northern analysis confirmed that expression was induced upon
      culturing of EC. Use of differential display to study endothelial gene expression
      will allow us to investigate the molecular mechanisms that underlie initiation
      and maintenance of endothelial differentiation.

PMID- 7713330
TI  - A monoclonal antibody that specifically reacts with human embryonal carcinomas,
      spermatogonia and oocytes is able to induce human EC cell death.
AB  - We developed a mouse monoclonal antibody, 6E2 (IgG3), against a human embryonal
      carcinoma (EC) cell line, NCR-G3, that possesses totipotent differentiation
      capabilities. Culturing human EC cells in the presence of 6E2 causes their death.
      It has been shown that 6E2 kills EC cells dose dependently. In
      immunohistochemical examination with normal human germ cells, 6E2 reacted
      specifically with spermatogonia and oocytes. Among human germ cell tumor tissues
      on aceton-fixed frozen sections, 6E2 reacted with embryonal carcinomas, seminomas
      and dysgerminomas, but it did not react with choriocarcinomas or with yolk sac
      tumors. Consistently, in flow cytometric analysis of cultured human germ cell
      tumor cell lines, 6E2 reacted exclusively with EC cells including NCR-G3 cells.
      It was revealed, by preserving its antigenicity after treatment with periodic
      acid and tunicamycin and by radiolabeling cells followed by immunoprecipitation,
      that the molecule defined by 6E2 is a cell surface protein having a molecular
      weight of approximately 80 kDa. These data illustrate that the molecule defined
      by 6E2 links human germ cell tumors, especially embryonal carcinoma, seminoma and
      dysgerminoma, to their normal counterparts and that it may play a role in
      survival and proliferation of human EC cells.

PMID- 7713331
TI  - Growth and gene expression in diploid epithelial cell lines derived from normal
      human parotid gland.
AB  - Secretions of salivary glands are essential for the maintenance of oral health.
      Due to the lack of suitable in vitro models, studies to examine biochemical and
      molecular mechanisms of the cellular secretions have been difficult. Furthermore,
      adequate quantities of human epithelial cells could not be obtained, because
      normal diploid cells are believed to exhibit a limited lifespan of two to three
      passages (40-50 population doublings). This report describes for the first time
      the development of two diploid epithelial acinar cell lines, HPAM1 and HPAF1,
      derived from the normal human parotid gland. The cell lines are propagated in
      serum-free medium comprised of keratinocyte basal medium supplemented with
      insulin (5 micrograms/ml), hydrocortisone (0.5 micrograms/ml), epidermal growth
      factor (EGF, 10 ng/ml), bovine pituitary extract (25 micrograms/ml), and
      antibiotics. The HPAM1 cell line has been passaged more than 50 times (> 189
      population doublings) and HPAF1 more than 40 times (> 185 population doublings).
      Both cell lines exhibit normal diploid karyotypes, lack transformed phenotypes
      and are non-tumorigenic in nude mice. Both cell lines produce tissue-specific
      proteins, i.e. alpha-amylase 1, basic proline-rich protein, and cystatins; and
      express the corresponding genes as determined by RT-PCR analyses. These results
      demonstrate that normal diploid human cells do not inherently exhibit limited
      life-span in vitro and can, under optimum conditions, be propagated indefinitely.

PMID- 7713332
TI  - Toxicologic principles do not support the banning of chlorine. A society of
      toxicology position paper.

PMID- 7713333
TI  - Subchronic feeding study of the mycotoxin fumonisin B1 in B6C3F1 mice and Fischer
      344 rats.
AB  - Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium moniliforme, a common
      fungus which occurs naturally on corn, and other Fusarium species. FB1 and other
      fumonisins are now recognized as having potentially important animal and human
      health implications. However, few toxicological data are currently available.
      Male and female B6C3F1 mice and Fischer 344 rats were fed diets containing 0, 1,
      3, 9, 27, or 81 ppm FB1 (> or = 98% purity) for 13 weeks. No differences in
      behavior or appearance, body weight or food consumption between control and FB1
      fed groups were found. In mice, hepatopathy and altered serum chemical profiles
      indicative of hepatotoxicity were found in females fed the 81 ppm diet. No
      adverse effects were found in female mice fed < or = 27 ppm FB1 or in male mice
      at any dietary level studied. In rats, nephrosis involving the outer medulla was
      found in males fed > or = 9 ppm and, to a lesser degree, in females fed 81 ppm
      FB1, while decreased kidney weight was found in both sexes at dietary levels > or
      = 9 ppm FB1. Although the liver is a target organ of FB1 in rats, hepatotoxicity
      was not found in rats fed diets containing up to 81 ppm FB1 for 90 days. Thus,
      FB1 was toxic to both species following subchronic oral exposure, although
      significant interspecies differences in the no observed effect levels and organ
      specific responses were found.

PMID- 7713334
TI  - Two-year inhalation exposure of female and male B6C3F1 mice and F344 rats to
      chlorine gas induces lesions confined to the nose.
AB  - Chlorine gas is a respiratory irritant in both animals and humans that produces
      concentration-dependent responses ranging from minor irritation to death. Female
      and male B6C3F1 mice and F344 rats were exposed to chlorine gas for up to 2 years
      to determine chronic toxicity and carcinogenicity. Groups of approximately 70
      each of female and male mice and rats were exposed to 0, 0.4, 1.0, or 2.5 ppm
      chlorine gas for 6 hr/day, 5 days/week (mice and male rats), or 3 alternate
      days/week (female rats) for 2 years, with an interim necropsy of rats at 12
      months (10 rats/sex/concentration group). A complete necropsy was performed on
      all animals. Histological examination was performed on all organs from high
      concentration and control animals and selected target organs from mid- and low
      concentration groups. Exposure-dependent lesions were confined to the nasal
      passages in all sex and species groups. Chlorine-induced lesions, which were most
      severe in the anterior nasal cavity, included respiratory and olfactory
      epithelial degeneration, septal fenestration, mucosal inflammation, respiratory
      epithelial hyperplasia, squamous metaplasia and goblet cell hypertrophy and
      hyperplasia, and secretory metaplasia of the transitional epithelium of the
      lateral meatus. Intracellular accumulation of eosinophilic proteinaceous material
      was also a prominent response involving the respiratory, transitional, and
      olfactory epithelia, and in some cases the squamous epithelium of the nasal
      vestibule. Many of these nasal lesions exhibited an increase in incidence and/or
      severity that was related to chlorine exposure concentration and were
      statistically significantly increased at all chlorine concentrations studied.
      Male mice and female rats appeared more sensitive to chlorine than female mice
      and male rats, respectively. The reasons for the sex differences within a species
      were not determined. Interspecies differences in regional dosimetry and site
      specific tissue susceptibility to chlorine exposure should be taken into account
      when using these data for accurate assessment of potential human health risks.
      The incidence of neoplasia was not increased by exposure, indicating that inhaled
      chlorine in rats and mice is an upper respiratory tract toxicant but not a
      carcinogen.

PMID- 7713335
TI  - Immunotoxicity--bridging the gap between animal research and human health
      effects.

PMID- 7713336
TI  - Carisoprodol: reproductive assessment by continuous breeding in Swiss mice.
AB  - Carisoprodol (CARI), a commonly prescribed neuromuscular relaxant, was evaluated
      for reproductive toxicity in Swiss CD-1 mice using the Reproductive Assessment by
      Continuous Breeding (RACB) protocol. Male and female mice were given CARI in corn
      oil suspension by daily gavage at doses of 0, 300, 750, and 1200 mg/kg body
      wt/day. Clinical signs of general toxicity in F0 animals included sedation,
      primarily in the high-dose group during the first week of exposure, and reduced
      body weight in high-dose females. CARI administration for 14 weeks did not affect
      the ability of the F0 animals to produce litters. However, decreases in
      proportion of pups born alive (4%) and absolute (5%) and adjusted live pup weight
      (7%) were observed at 1200 mg/kg CARI when compared to controls. In a crossover
      mating trial to determine the affected sex, there were no significant differences
      in the measured reproductive parameters. CARI at the high dose increased the
      proportion of time spent in proestrus and estrus, but cycle length was
      unaffected. At F0 necropsy (Week 27 of treatment), all sperm parameters were
      normal. Right epididymis and liver weights, relative to body weight, were
      increased (12 and 23%, respectively) over the control group for high-dose males.
      A mating trial to determine the fertility and reproductive competence of the F1
      generation showed no effect of CARI on indices of mating, pregnancy, or
      fertility, the proportion of F2 pups born alive, the sex ratio of live F2 pups,
      live F2 pup weight, or gestation length.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713337
TI  - Kinetics of hemoglobin and albumin adducts in rabbits subchronically exposed to
      benzo[a]pyrene.
AB  - Benzo[a]pyrene (BaP) can form adducts with proteins after activation to a
      diolepoxide. Benzo[a]pyrene-hemoglobin and BaP-albumin adducts were measured in
      rabbits exposed to 0.5 or 5 mumol.kg-1.week-1 for a total of 11 weeks (last
      injection on Day 75). Each dose group of nine rabbits was divided into three
      equal subgroups. For each dose, one subgroup received a single weekly injection
      (Mondays), the second had two equal weekly injections (Mondays and Thursdays),
      and the third had five weekly injections (Mondays through Fridays). Blood was
      collected prior to injection on Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 77, 78,
      80, 84, 92, 108, and 140 for adducts determinations, with Day 0 being a Monday.
      The measured concentration of hemoglobin adducts was independent of the frequency
      of administration for a given total weekly dose giving support to its value as a
      "biointegrator." In addition, animals injected with 0.5 and 5 mumol BaP.kg-1.week
      1 had respective mean adduct concentrations of 0.3 and 3 pmol/g hemoglobin. The
      blood concentration of albumin adducts was related to the frequency of injection
      with the animals receiving one, two and five injections/week having the lowest,
      intermediate, and highest adduct concentrations, respectively. Animals injected
      with 0.5 and 5 mumol BaP.kg-1.week-1 had respective mean adduct concentrations of
      5 and 20 pmol/g which are 17 and 7 times higher than their corresponding
      hemoglobin adducts' values. The corresponding albumin adducts' half-lives
      calculated from the day of cessation of exposure were 5.8 and 9.6 days, compared
      with a reported 5.7 days for the half-life of the intact protein.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7713339
TI  - The question of multiple chemical sensitivity.

PMID- 7713338
TI  - The importance of pharmacokinetics in determining the relative potency of 2,3,7,8
      tetrachlorodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans induce exthoxyresorufin-O
      deethylase (EROD) activity, a marker for CYP1A1. Differences in potency of these
      compounds can be attributed to differences in their affinity for the Ah receptor
      as well as differences in pharmacokinetics. To test the role of pharmacokinetics
      in the in vivo potency of these chemicals, 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) were administered to female
      B6C3F1 mice for 4 or 13 weeks of treatment and EROD activity in liver and skin
      was determined. The doses were designed to be equally potent based on the
      published Toxic Equivalency Factor (TEF) values for these compounds. Mice
      received either 150 ng TCDD/kg/day or 1500 ng TCDF/kg/day, 5 days/week for either
      4 or 13 weeks. At 4 weeks, hepatic EROD was induced 11- and 7-fold by TCDD and
      TCDF, respectively. These data indicate that the published TEFs accurately
      estimated the relative potency of TCDF after 4 weeks of treatment. After 13
      weeks, hepatic EROD was induced 41- and 6-fold by TCDD and TCDF, respectively.
      The TEFs did not accurately estimate the relative inductive potency of these
      compounds when compared after 13 weeks of treatment. The inability of the TEFs to
      predict the relative potency of these compounds after 13 weeks of treatment may
      be due in part to the differences in the pharmacokinetic properties of each
      congener. The half-life of TCDF and TCDD is approximately 2 and 15 days,
      respectively. Steady-state levels of TCDD were not attained by 4 weeks, which is
      reflected in the increase in hepatic EROD between 4 and 13 weeks. In contrast,
      steady-state levels of TCDF were reached within 4 weeks.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7713340
TI  - Assessment of cutaneous and ocular irritancy: a decade of research on
      alternatives to animal experimentation.
AB  - Over the past decade increasing societal and scientific pressure has promoted the
      development of alternatives to local tolerance testing in laboratory animals. The
      use of isolated organs, fertilized hen's eggs, and cell culture systems has been
      proposed as well as the study of a toxicant's biochemical effects and structure
      activity relationships. This paper critically reviews the current status of these
      approaches and discusses the preliminaries for the establishment of alternative
      methods in the process of safety assessment.

PMID- 7713341
TI  - Environmental tobacco smoke: experimental facts and societal issues.
AB  - Involuntary exposure to environmental tobacco smoke (ETS) in public or in working
      places is considered to be a serious risk to human health. This symposium
      addressed several issues of toxicological interest that are associated with
      exposure to ETS. Epidemiologic evidence obtained in human studies suggests that
      "passive smoking" increases the risk of developing lung cancer in nonsmokers and
      favors the development of respiratory tract infections in children. Comparatively
      few data are available from animal studies that provide experimental support of
      the observations. Exposure of pregnant or neonate rats to cigarette sidestream
      smoke (SS) affects developmental patterns of drug metabolizing enzymes that may
      persist up to 90 days. In young roosters, SS accelerates the development of
      arteriosclerotic plaques. On the other hand, exposure of adult rats for up to 90
      days induces only transient signs of damage in the nasal passages, but not in the
      deep lung, and this only at extremely high concentrations of ETS. So far,
      experimental toxicology has provided comparatively few data on the correlation
      between exposure to ETS and adverse health effects. yet, such data are needed,
      particularly since many conclusions drawn from the epidemiological studies remain
      open to criticism and questions.

PMID- 7713342
TI  - Ozone adaptation in rats after chronic exposure to a simulated urban profile of
      ozone.
AB  - Studies in both humans and rats have indicated that certain pulmonary responses
      induced by exposure to an acute provocative concentration of ozone (O3) will
      eventually attenuate if the exposure is repeated on a daily basis. This
      phenomenon is commonly referred to as O3 adaptation. Whether or not a "state" of
      adaptation develops due to long-term low level O3 exposure is unknown. Two human
      studies have reported adaptation in subjects living in Los Angeles during periods
      when ambient O3 concentrations have been relatively high. At present, however, we
      are not aware of comparable information from rats. This study assessed O3
      adaptation in rats following chronic (12 or 18 months) exposure and after a 4
      month recovery period. A chronic exposure pattern, similar to that found in an
      urban area during the summer (0.06 ppm O3 for 13 hr/day, 7 days/week; Monday
      Friday, peak to 0.25 ppm O3, over 9 hr), was used. To assess whether adaptation
      had occurred and/or persisted, awake rats were challenged with high provocative
      concentrations of O3 for up to 2 hr. During a challenge, rats were monitored for
      typical O3-induced alterations in spontaneous breathing parameters (e.g.,
      increase in breathing frequency and decrease in tidal volume). Adaptation was
      defined as attenuation of breathing response during the challenge in rats
      chronically exposed to O3 as compared to that in "control" rats (chronically
      exposed to air). Adaptation was found in the rats within 8 hr following the
      chronic O3 exposure but not after the 4-month recovery period. Spontaneous
      breathing parameters that were significantly attenuated in the chronically
      exposed rats were breathing frequency, tidal volume, inspiratory and expiratory
      times, and maximum expiratory flow. We conclude that rats demonstrated adaptation
      to O3 after long-term exposure to an urban-type O3 profile and that the
      adaptation was not seen 4 months postexposure. These results suggest that
      exposure to environmental O3 in Los Angeles air may have been responsible for the
      adaptation found in residential subjects.

PMID- 7713343
TI  - Comparative skin phototoxicity in mice with two photosensitizing drugs:
      benzoporphyrin derivative monoacid ring A and porfimer sodium (Photofrin).
AB  - Benzoporphyrin derivative monoacid ring A (BPD-MA) and Photofrin (porfimer
      sodium) are photodynamic anticancer agents. The chemical structures of the two
      regioisomers of BPD-MA are 9-methyl trans-(+/-)-18-ethenyl-4,4 alpha-dihydro-3,4-
      bis(methoxycarbonyl)-4 alpha, 8,14,19-tetramethyl-4,4 alpha-dihydro-3,4-
      bis(methoxycarbonyl)-4 alpha, 8,14,19-tetramethyl-23H,25H-benzo(b)porphine- 9,13
      dipropanoate and 13-methyl-trans-(+/-)-18-ethenyl-4,4 alpha-dihydro-3,4-
      bis(methoxycarbonyl)-4 alpha, 8,14,19-tetramethyl-23H,25H-benzo(b)porphine- 9,13
      dipropanoate. Photofrin (a registered trademark of American Cyanamid Co.) is a
      polyporphrin oligomer containing ester and ether linkages. The ability of BPD-MA
      or Photofrin to cause skin phototoxicity was investigated in mice exposed to
      simulated sunlight (light) 3, 24, or 48 hr after receiving a single intravenous
      injection of vehicle or 2, 10, or 20 mg/kg of BPD-MA or Photofrin. The data were
      from two studies conducted using male and female CD1 mice (approximately 7 weeks
      old). The hair of the dorsal thoracic area was clipped 24 hr prior to exposure to
      light. Mice were exposed to light for 5 min. The clipped area of skin was the
      primary site for the evaluation of phototoxicity. Mice were observed for 2 weeks
      after treatment. There were no significant findings in controls or in mice given
      2 mg/kg of BPD-MA. When mice were exposed to light 3 hr after dosing, both BPD-MA
      (10 or 20 mg/kg) and Photofrin (2, 10 or 20 mg/kg) caused phototoxicity. Death
      occurred in all mice given 20 mg/kg of BPD-MA or Photofrin, and in the majority
      of mice given 10 mg/kg of Photofrin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713344
TI  - Evaluation of the developmental toxicity of ethylene glycol aerosol in the CD rat
      and CD-1 mouse by whole-body exposure.
AB  - Ethylene glycol (EG) is a major industrial chemical, shown to be teratogenic at
      high doses by gavage in rodents. Since one route of industrial exposure is to the
      aerosol at high concentrations, timed-pregnant CD rats and CD-1 mice were
      exposed, whole-body, to a respirable aerosol of EG (mass median aerodynamic
      diameter, 2.3 microns) on Gestational Days (GD) 6 through 15 for 6 hr per day at
      target exposure concentrations of 0, 150, 1000, or 2500 mg/m3 (analytical
      concentrations of 0, 119 +/- 13, 888 +/- 149, and 2090 +/- 244 mg/m3,
      respectively), with 25 plug-positive animals per species per group. Clinical
      observations and maternal body weights were documented throughout gestation for
      both species. Maternal food and water consumption was measured in rats only
      throughout gestation. At scheduled necropsy (GD 21 for rats, GD 18 for mice),
      maternal animals were evaluated for body weight, liver weight, kidney weight,
      gravid uterine weight, number of ovarian corpora lutea, and status of
      implantation sites, i.e., resorptions, dead fetuses, live fetuses. Fetuses were
      dissected from the uterus, counted, weighed, sexed, and examined for external,
      visceral, and skeletal malformations and variations. All rat dams survived to
      scheduled termination. Minimal maternal toxicity was indicated by a significant
      increase in absolute and relative liver weight at 2500 mg/m3. Food and water
      consumption, maternal body weights and weight gain, and maternal organ weights
      (other than liver) were unaffected by exposure. Gestational parameters were
      unaffected by exposure, including pre- and post-implantation loss, live
      fetuses/litter, sex ratio, and fetal body weight/litter. There was no treatment
      related increase in the incidence of any individual malformation, in the
      incidence of pooled external, visceral, or skeletal malformations, or in the
      incidence of total malformations by fetus or by litter. There were no increases
      in the incidence of external or visceral variations. Evidence of fetotoxicity,
      expressed as reduced ossification in the humerus, the zygomatic arch, and the
      metatarsals and proximal phalanges of the hind-limb, was observed at 1000 and
      2500 mg/m3. All mouse dams survived to scheduled termination. One dam at 2500
      mg/m3 was carrying a totally resorbed litter at termination. Maternal toxicity
      was observed at 1000 and 2500 mg/m3, expressed as reduced body weight and weight
      gain during and after the exposure period, and reduced gravid uterine weight.
      (Maternal effects may have been due, in part or whole, to effects on the
      conceptuses; see below.)(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7713345
TI  - Effect of chronic cigarette smoke exposure on lung clearance of tracer particles
      inhaled by rats.
AB  - Cigarette smoking can influence the pulmonary disposition of other inhaled
      materials in humans and laboratory animals. This study was undertaken to
      investigate the influence of cigarette smoke exposures of rats on the pulmonary
      clearance of inhaled, relatively insoluble radioactive tracer particles.
      Following 13 weeks of whole-body exposure to air or mainstream cigarette smoke
      for 6 hr/day, 5 days/week at concentrations of 0, 100, or 250 mg total
      particulate matter (TPM)/m3, rats were acutely exposed pernasally to 85Sr-labeled
      fused aluminosilicate (85Sr-FAP) tracer particles, then air or smoke exposures
      were resumed. A separate group of rats was exposed to the 85Sr-FAP then serially
      euthanized through 6 months after exposure to confirm the relative insolubility
      of the tracer particles. We observed decreased tracer particle clearance from the
      lungs that was smoke concentration-dependent. By 180 days after exposure to the
      tracer aerosol, about 14, 20, and 40% of the initial activity of tracer was
      present in control, 100 mg TPM/m3, and 250 mg TPM/m3 groups, respectively. Body
      weight gains were less in smoke-exposed rats than in controls. Smoke exposure
      produced lung lesions which included increased numbers of pigmented alveolar
      macrophages distributed throughout the parenchyma and focal collections of
      enlarged alveolar macrophages with concomitant alveolar epithelial hyperplasia
      and neutrophilic alveolitis. The severity of the lesions increased with smoke
      exposure duration and concentration to include interstitial aggregates of
      pigmented macrophages and interstitial fibrosis. Our data confirm previous
      findings that exposure to cigarette smoke decreases the ability of the lungs to
      clear inhaled materials. We further demonstrate an exposure-concentration related
      magnitude of effect, suggesting that the cigarette smoke-exposed rat constitutes
      a useful model for studies of the effects of cigarette smoke on the disposition
      of inhaled particles.

PMID- 7713346
TI  - Cyanide antagonism with carrier erythrocytes and organic thiosulfonates.
AB  - Previous studies reported that resealed erythrocytes containing rhodanese (CRBC)
      and NA2S2O3 rapidly metabolize cyanide to the less toxic thiocyanate both in
      vitro and in vivo. This provided a new conceptual approach to prevent and treat
      cyanide intoxication. Although the rhodanese-containing carrier cells with
      thiosulfate as the sulfur donor were efficacious, this approach has potential
      disadvantages, as thiosulfate has limited penetration of cell membrane and
      product inhibition of rhodanese can occur due to inorganic sulfite accumulation.
      In order to circumvent substrate limitation and product inhibition by sodium
      thiosulfate, organic thiosulfonates were explored. These thiosulfonates have
      higher lipid solubility than thiosulfate and therefore can replenish the depleted
      sulfur donor, as they can readily penetrate cell membranes. Also, product
      inhibition of rhodanese is less apt to occur. This change in sulfur donors should
      greatly enhance cyanide detoxication, replenish the sulfur donor, and minimize
      product inhibition of rhodanese. Present studies demonstrate the enhanced
      efficacy of exogenous organic thiosulfonates over sodium thiosulfate in the CRBC
      antidotal system to detoxify the lethal effects of cyanide either alone or in
      combinations with exogenously administered NaNO2. Murine carrier erythrocytes
      containing purified bovine liver rhodanese were administered intravenously into
      male Balb/C mice. Subsequently, butanethiosulfonate (BTS) or Na2S2O3 (ip), and
      NaNO2 (sc) were co-administered prior to KCN (sc). Potency ratios, derived from
      the LD50 values, were compared in groups of mice treated with CRBC-Na2S2O3 or
      CRBC-BTS either alone or in combination with NaNO2.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7713347
TI  - Comparison of the relative inhibition of acetylcholinesterase and neuropathy
      target esterase in rats and hens given cholinesterase inhibitors.
AB  - Inhibition of neuropathy target esterase (NTE, neurotoxic esterase) and
      acetylcholinesterase (AChE) activities was compared in brain and spinal cords of
      adult While Leghorn hens and adult male Long Evan rats 4-48 hr after
      administration of triortho-tolyl phosphate (TOTP po, 50-500 mg/kg to hens; 300
      1000 mg/kg to rats), phenyl saligenin phosphate (PSP im 0.1-2.5 mg/kg to hens; 5
      24 mg/kg to rats), mipafox (3-30 mg/kg ip to hens and rats), diisopropyl
      phosphorofluoridate (DFP sc, 0.25-1.0 mg/kg to hens; 1-3 mg/kg to rats),
      dichlorvos (5-60 mg/kg ip to hens; 600-2000 mg/kg to rats), and carbaryl (300-560
      mg/kg ip to hens; 30-170 mg/kg to rats). Inhibitions of NTE and AChE were dose
      related after administration of all compounds to both species. Hens and rats
      given TOTP, PSP, mipafox, and DFP demonstrated delayed neuropathy 3 weeks later,
      with spinal cord lesions and clinical signs more notable in hens. Ratios of
      NTE/AChE inhibition in hen spinal cord, averaged over the doses used, were 2.6
      after TOTP, 5.2 after PSP, 1.3 after mipafox, and 0.9 after DFP, which contrast
      with 0.53 after dichlorvos, 1.0 after malathion, and 0.46 after carbaryl. Rat
      NTE/AChE inhibition ratios were 0.9 after TOTP, 2.6 after PSP, 1.0 after mipafox,
      0.62 after DFP, 1.3 after dichlorvos, 2.2 after malathion, and 1.1 after
      carbaryl. The lower NTE/AChE ratios in rats given dosages of the four
      organophosphorus compounds that caused delayed neuropathy interferred with
      survival, an effect that was not a problem in hens.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7713348
TI  - The effects of various drugs on the myocardial inotropic response.
AB  - 1. The signal transduction process mediated by cyclic AMP that leads to the
      characteristic positive inotropic effect (PIE) in association with a positive
      lusitropic effect (acceleration of rate of twitch relaxation) has been well
      established. Relationships between accumulation of cyclic AMP, changes in
      intracellular Ca2+ transients and the PIE differ, however, depending on the
      mechanism of particular drugs that affect different steps in the metabolism of
      cyclic AMP. Selective partial agonists of beta 1-adrenoceptors and inhibitors of
      phosphodiesterase (PDE) III cause the accumulation of less cyclic AMP for a given
      PIE than does isoproterenol. In addition, in aequorin-microinjected canine
      ventricular muscle, selective inhibitors of PDE III, OPC 18790 and Org 9731,
      produced smaller decreases in the responsiveness of myofilaments to Ca2+ ions
      than isoproterenol, while a partial agonist of beta 1-adrenoceptors, denopamine,
      elicits a decrease in Ca2+ responsiveness of the same extent as does
      isoproterenol. 2. Activation of myocardial alpha 1-adrenoceptors, as well as
      stimulation of receptors for endothelin and angiotensin II, which accelerates
      hydrolysis of phosphoinositide (PI) to result in production of inositol 1,4,5
      trisphosphate (IP3) and diacylglycerol (DAG) are associated with very similar
      inotropic regulation: (1) the dependence on the species of animals of induction
      of the PIE; (2) an excellent correlation between the extent of acceleration of
      hydrolysis of PI and the PIE; (3) isometric contraction curves associated with a
      negative lusitropic effect; (4) the PIE associated with increases in myofibrillar
      responsiveness to Ca2+ ions; and (5) the selective inhibition of the PIE by an
      activator of protein kinase C (PKC), phorbol 12,13-dibutyrate (PDBu), with little
      effect on the PIE of isoproterenol and Bay k 8644. 3. A novel class of
      cardiotonic agents, namely, Ca2+ sensitizers such as EMD 53998 and Org 30029, act
      on the Ca(2+)-binding site of troponin C, increasing the affinity of these sites
      for Ca2+ ions, or at the actin-myosin interface to facilitate the cycling of
      cross-bridges. These agents produce a PIE with little change or decrease in Ca2+
      transients and may bring about a significant breakthrough in the development of
      drugs for reversal of myocardial failure in the treatment of congestive heart
      failure.

PMID- 7713349
TI  - Peroxidative xenobiotic oxidation by partially purified peroxidase and
      lipoxygenase from human fetal tissues at 10 weeks of gestation.
AB  - 1. Present study reports the ability of partially purified peroxidase and
      lipoxygenase from human fetal tissues at 10 weeks of gestation to oxidize
      selected xenobiotics in vitro. 2. Peroxidase was found to oxidize four different
      chemicals in the presence of H2O2. Sodium azide and potassium cyanide inhibited
      peroxidase activity towards guaiacol in a concentration-dependent manner. 3. The
      dioxygenase and co-oxidase activities of lipoxygenase towards linoleic acid and
      four model xenobiotics, respectively, were observed. Both the catalytic
      activities of lipoxygenase were significantly inhibited by < 1.0 microM
      nordihydroguaiaretic acid. 4. These findings suggest that peroxidase and
      lipoxygenase may be important pathways for peroxidative xenobiotic oxidation in
      human fetal tissues.

PMID- 7713350
TI  - Effects of hypoxia, mechanical and chemical endothelium denudation on guinea-pig
      isolated pulmonary arteries.
AB  - 1. The isolated unstimulated main trunk, extralobar and intralobar branches of
      the pulmonary artery of the guinea-pig developed well-sustained contractions upon
      exposure to hypoxia (95% N2-5% CO2 gas mixture; PO2 11-15 mm Hg). The
      contractions were readily reversible by reoxygenation (95% O2-5% CO2). 2.
      Mechanical removal of the endothelium did not significantly affect the magnitude
      of the hypoxia-induced contractions in rings obtained from the main trunk of the
      pulmonary artery but reduced those of rings obtained from the proximal and distal
      extralobar branches. 3. Mechanical removal of the endothelium also did not affect
      the magnitude of contractions induced by BaCl2 in the main but significantly
      reduced contractions induced by the same agent in the proximal and distal
      extralobar branches of the pulmonary artery, suggesting that the reduction of
      hypoxia-induced contractions in the endothelium-denuded rings is due to
      impairment of vascular reactivity. 4. Pretreatment with L-N-nitro arginine, an
      inhibitor of the synthesis of the endothelium-derived relaxing factor, did not
      significantly affect the hypoxia-induced contractions but increased the magnitude
      of BaCl2-induced contractions in the main and the extralobar branches. 5. These
      observations demonstrate that isolated pulmonary artery rings of the guinea-pig
      develop slow contractions in response to hypoxia without prior contraction with
      an agonist, and that the endothelium plays little role in the hypoxia-induced
      contractions of guinea-pig isolated large pulmonary arteries. 6. Furthermore,
      these observations suggest that the effect of mechanical endothelium denudation
      or pharmacological manipulation, such as EDRF inhibition, on vascular reactivity
      should be considered when the effect of hypoxia is studied in isolated pulmonary
      arteries.

PMID- 7713351
TI  - Direct cellular immunomodulation produced by diacetylmorphine (heroin) or
      methadone.
AB  - 1. Abuse of the narcotic drug diacetylmorphine (heroin), as well as methadone, a
      drug for treating heroin addiction, has been associated with alterations in
      immune function in humans. The current study was performed to assess the direct
      (in vitro) immunomodulatory effect of exposure to these drugs, in view of the
      very limited studies reported thus far on this effect. 2. Murine splenocytes or
      peritoneal macrophages were cultured in vitro at concentrations of 0.0001-100
      microM heroin or methadone. B-cell function was assessed by quantitating cellular
      proliferation in response to stimulation with an antigen analog; T-cell
      regulatory function was assessed by culturing splenocytes with or without drugs
      in the presence of anti-CD3 antibody and subsequently quantitating cytokine
      production; and T-cell effector function was evaluated by culturing lymphocytes
      with or without drugs during a 5-day induction culture followed by assessment of
      specific cytotoxic T-lymphocyte (CTL) activity. Natural immunity was assessed by
      quantitating basal and IL-2 augmented natural killer (NK) cell function, and
      macrophage function was assessed by cytokine production. 3. In vitro exposure to
      heroin resulted in decreased B-cell proliferation at concentrations of 1-100
      microM, and methadone had a similar effect at concentrations of 0.1-100 microM.
      4. Production of IL-2 was suppressed by 0.1-100 microM of heroin, whereas
      exposure to methadone appeared to result in a generalized modulation, with
      suppression of IL-2 at most concentrations. In contrast, IL-4 production was only
      affected at the 100 microM concentration of both drugs.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7713353
TI  - Kidney drug metabolizing activities in streptozotocin diabetic rats.
AB  - 1. Streptozotocin-induced diabetes produced significant changes on the drug
      metabolizing enzyme machinery of rat kidney microsomes. 2. It reduced the
      cytochrome P-450 content by 30%, this effect being reversed by insulin therapy.
      3. Total androstenedione oxidative metabolism was increased 2.5-fold and insulin
      treatment partially antagonized this activation. 4. Total testosterone
      hydroxylase activities were not modified by diabetes nor by insulin but the
      formation of 2 alpha OH testosterone and 6 beta OH testosterone were distinct in
      diabetes or insulin treated diabetic rats. 5. Only UDP-glucuronyltransferase
      activity for PNP was found in kidney microsomes. Diabetes determined a lower
      UDPGT substrate efficiency not reversed by insulin therapy.

PMID- 7713352
TI  - Down-regulation of N-methyl-D-aspartate (NMDA) receptors of brain regions and
      spinal cord of rats treated chronically with morphine.
AB  - 1. The effects of morphine tolerance and abstinence on the characteristics of N
      methyl-D-aspartate (NMDA) receptors, labeled with [3H]MK-801, were determined in
      the brain regions and spinal cord of the rat. 2. Male Sprague-Dawley rats were
      rendered tolerant to and physically dependent on morphine by subcutaneous
      implantation of six morphine pellets during a 7-day period. In tolerant (non
      abstinent) rats, the pellets were left intact at the time of sacrificing, whereas
      in the abstinent rats the pellets were removed 16 hr prior to sacrificing. 3. The
      binding of [3H]MK-801, an NMDA receptor antagonist, to membranes prepared from
      spinal cord and brain regions (cortex, striatum, amygdala, hippocampus,
      hypothalamus, midbrain and pons-medulla) was determined using 5 nM concentration
      of the ligand in the presence of 30 microM glycine and 50 microM of glutamate. 4.
      In non-abstinent morphine tolerant rats, the binding of [3H]MK-801 was decreased
      by 40 and 33% in the midbrain and spinal cord, respectively, in comparison with
      their placebo controls. In morphine abstinent rats, the binding of [3H]MK-801 was
      decreased by 42, 29 and 50% in hypothalamus, midbrain and spinal cord,
      respectively, in comparison with their placebo controls. The binding of [3H]MK
      801 to other brain regions and spinal cord of morphine tolerant and abstinent
      rats did not differ from their respective placebo controls. 5. Thus, these
      studies demonstrate, for the first time, that in the presence of glutamate and
      glycine, NMDA receptors of selected brain regions and spinal cord are down
      regulated in rats treated chronically with morphine.

PMID- 7713354
TI  - Effect of N omega-nitro-L-arginine methyl ester on cardiac haemodynamic responses
      to adenosine infusion in conscious rats.
AB  - 1. The aim of the present study was to evaluate the role of NO in the
      cardiovascular effects of adenosine in conscious rats. 2. Cardiac index was
      determinated by thermodilution. In a group of rats, three doses of adenosine were
      infused (i.v.) at a rate of 150, 300 and 450 micrograms/kg/min in the absence and
      in the presence of L-NAME (10 mg/kg). In a second group of rats, the experimental
      protocol was the same as that of the first group, except an infusion of
      methoxamine (50 micrograms/kg/min) was given during the second adenosine
      administration, instead of L-NAME. 3. In the absence of L-NAME or methoxamine,
      adenosine induced a dose-dependent decrease in mean arterial pressure and an
      increase in vascular conductance although adenosine did not affect cardiac index.
      4. L-NAME administration attenuated the decreasing effect on the mean arterial
      pressure in response to the two lower doses of adenosine. In the presence of L
      NAME, adenosine induced a significant increase in cardiac index from 18.7 +/- 1.5
      to 29.1 +/- 1.9 and 26.2 +/- 1.4 ml/min/100 g. Administration of L-NAME
      significantly attenuated the adenosine-induced increase in vascular conductance.
      5. Methoxamine infusion induced an enhanced response to adenosine infusion. In
      the presence of methoxamine, adenosine induced a significant greater decrease in
      mean arterial pressure, and increase in cardiac index and vascular conductance.
      6. These results indicate that part of the cardiovascular effects of adenosine
      can be mediated by NO, since L-NAME administration partially blocked the
      adenosine-induced vasodilatation.

PMID- 7713355
TI  - Endothelium-derived hyperpolarizing factor does not contribute to the decrease in
      endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic
      rats.
AB  - 1. We examined the contribution of endothelium-derived hyperpolarizing factor
      (EDHF) to the impairment of endothelium-dependent relaxation caused by
      acetylcholine (ACh) in the aorta of streptozotocin-induced diabetic rats, by
      using N omega-L-nitro-arginine methylester (L-NAME) and tetraethylammonium
      chloride (TEA) to inhibit nitric oxide (NO) and EDHF, respectively. 2. ACh
      induced relaxation of the aorta decreased in diabetic rats. In contrast, sodium
      nitroprusside-induced relaxation was the same in diabetic rats and control rats.
      3. Treatment with 5 x 10(-7) M L-NAME resulted in a right shift of the dose
      response curves of ACh-induced relaxation in the aorta. The shift was greater in
      the control aorta. 4. Treatment with 5 x 10(-4) M TEA resulted in a similar right
      shift in both the control and diabetic aorta. 5. Therefore, while endothelium
      derived NO appears to contribute to the impairment of ACh-induced endothelium
      dependent relaxation in the aorta of diabetic rats, EDHF does not.

PMID- 7713356
TI  - A lack of supersensitivity to opioid receptor agonists following chronic spinal
      opioid receptor antagonist administration in the rat.
AB  - 1. Male Sprague-Dawley rats were chronically tested with intrathecal (i.t.)
      receptor selective opioid antagonists to determine if antinociceptive
      supersensitivity developed to selective i.t. opioid receptor agonists. 2. A
      subcutaneously implanted osmotic minipump was used to deliver the mu-opioid
      receptor antagonist CTOP (0.3 nmol) or the delta-opioid receptor antagonist
      naltrindole (5.5 nmol) for 7 days. 3. Following a 24 hr washout period, rats
      received a single i.t. dose (ED50) of either DAMPGO (for CTOP-treated animals) or
      DPDPE (for naltrindole-treated animals) and the antinociceptive effects of the
      agents were tested on the tail-flick test. 4. Our findings revealed that chronic
      spinal treatment with selective opioid receptor antagonists did not induce an
      antinociceptive supersensitivity to selective opioid receptor agonists. 5.
      Perhaps this lack of supersensitivity is reflective of difficulties inherent to
      opioid receptor antagonists that do not possess negative intrinsic activity.

PMID- 7713357
TI  - Effects of preanesthetic and anesthetic drugs on endothelium-dependent responses
      in the rat aorta.
AB  - 1. Acetylcholine often fails to induce endothelium-dependent relaxation in human
      vessels in vitro. Due to the fact that most of these vessels come from surgery,
      we examined the influence of drugs used in anesthesia on endothelium-dependent
      responses in rat aorta. 2. Groups of male Wistar rats of the following treatments
      were utilized: P group, diazepam+promethazine+atropine; I group,
      pentothal+succinylcholine; IG group, halothane+nitrous oxide; M group,
      morphine+pancuronium; C group, untreated rats. Dose-response curves to
      noradrenaline and acetylcholine were determined in rat aorta in vitro, in the
      presence and absence of endothelium. 3. Acetylcholine induced more relaxation (P
      < 0.05) in the rat aorta of IG group compared with that of the C group. 4. In the
      rat aorta from P and IG groups, the contractions produced by several
      concentrations of noradrenaline were significantly smaller (P < 0.05) when the
      endothelium was removed. Similar effects occurred in aorta strips of animals
      previously treated with either atropine, promethazine, cimetidine or halothane.
      5. Our results suggest that drugs currently used in anesthesia interfere with
      some endothelium-dependent effects on isolated rat aorta but according to these
      results they do not seem to be responsible for the lack of acetylcholine
      relaxation sometimes described in human vessels in vitro.

PMID- 7713358
TI  - The sigma-selective ligand NE-100 attenuates the effect of phencyclidine in a rat
      diving model.
AB  - 1. Phencyclidine (PCP) reduces the latency of rats diving into a water-filled
      pool from a hidden platform, without stereotyped behavior. 2. The sigma-selective
      ligand, NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethyl-amine
      monohydrochloride), attenuates the effects of PCP in this procedure. 3. The
      serotonin2 (5-HT2) antagonist, ritanserin, and the sigma receptor ligands, 1
      (cyclopropylmethyl)-4-[2'(4"-fluorophenyl)-2'-oxoethyl]- piperidine HBr (Dup734),
      4-[2'-(4"-cyanophenyl)-2'-oxoethyl]-1- (cyclopropylmethyl)piperidine (XJ448),
      alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY14802)
      and rimcazole similarly attenuate the effects of PCP. 4. The dopamine D2/sigma
      ligands, haloperidol and cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-2-methoxy-5
      chloro-4- methylaminobenzamide (YM-09151-2) completely reverse the effects of
      PCP, whereas the same dose ranges of these drugs produce sedation. 5. The
      dopamine D2-selective antagonist, sulpiride, has no apparent effect on the PCP
      latency to the rat dive. 6. Thus, PCP-induced diving behavior was improved by
      sigma ligands and the 5-HT2 antagonist. This model of negative symptoms in an
      experimental animal will facilitate experiments on drug treatments for
      schizophrenia.

PMID- 7713359
TI  - Endothelin ETA receptor antagonist, BQ-123, blocks the vasoconstriction induced
      by sarafotoxin 6b in the heart but not in other vascular beds.
AB  - 1. The cardiovascular effects of SRT6b in control and BQ-123, a specific ETA
      receptor antagonist, pretreated rats were determined in anesthetized rats using a
      radioactive microsphere technique. 2. Infusion of SRT6b produced an increase in
      blood pressure and total peripheral resistance, decrease in cardiac output and
      stroke volume, and no change in heart rate of control or BQ-123 treated rats. 3.
      SRT6b induced a decrease in blood flow to the heart which was completely blocked
      by BQ-123 pretreatment. The decrease in blood flow to other organs by SRT6b was
      not affected by BQ-123 pretreatment. 4. This study indicates that ET receptors in
      the coronary blood vessels are of a different type (neither ETA nor ETB) to those
      in other vascular beds.

PMID- 7713360
TI  - Spontaneous bursting induced by convulsant agents in an identified insect
      neurone.
AB  - 1. Using an in vitro preparation, intracellular recordings were made from the
      cell body of the "fast" coxal depressor motoneurone (Df) from the cockroach,
      Periplaneta americana. 2. This cell was normally quiescent in the absence of
      injected current but could respond to applied depolarizing current with one or
      more plateau potentials: regenerative depolarizations which can drive production
      of axonal impulses. However, when the convulsant agents picrotoxin (PTX; 10(-5)
      M) or pentylenetetrazole (PeTZ; 25 mM) were applied Df exhibited spontaneous
      bursting behaviour. 3. The bursting activity induced by the two agents was
      qualitatively different. The bursting pattern induced by PTX was irregular and
      occurred only after a delay of 20-40 min; the transformation to bursting activity
      occurred without any consistent changes in membrane potential and effective
      membrane resistance (5.9 +/- 0.4 M omega; n = 25; mean +/- SEM) remained
      unchanged (P > 0.1). PTX did not induce spontaneous bursting or cause a
      significant change in plateau potential threshold or membrane potential in
      isolated somata. Therefore, it appeared to exert its actions or more distant
      regions of the neurone, probably by enhancing the effects of excitatory synaptic
      input. 4. In contrast, PeTZ rapidly (30 sec-2 min) induced regular bursting
      activity. This agent could also produce spontaneous bursting activity in isolated
      somata; thus it exerted its actions primarily upon intrinsic membrane properties,
      although it also enhanced the effects of electrically driven synaptic stimulation
      of the non-isolated Df somata. 5. Experiments with PTX also revealed that
      bursting could be recorded in cells in which it was not possible to evoke plateau
      potentials by electrically depolarizing the soma. This suggests that other
      regions of the cell possess the machinery necessary to produce burst-like
      behaviour.

PMID- 7713361
TI  - The modified light/dark transition test in mice: evaluation of classic and
      putative anxiolytic and anxiogenic drugs.
AB  - 1. We devised a new light/dark transition apparatus, recorded transitions, % time
      animals spent outside the dark chambers (% time) and locomotor activity, and
      evaluated this apparatus by testing anxiolytics, non-anxiolytic drugs and
      putative anxiogenic drugs in mice. 2. Diazepam and alprazolam significantly
      increased transitions, % time and locomotor activity. The effects of 1 mg/kg
      (i.p.) diazepam on these parameters in this modified test were blocked by
      flumazenil, a selective benzodiazepine antagonist. 3. Anxiogenic drugs such as
      beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) and picrotoxin
      significantly decreased all three parameters. Another anxiogenic drug, yohimbine,
      also significantly decreased transitions and locomotor activity, but it
      significantly increased % time at 5 mg/kg (i.p.). 4. Imipramine (5-10 mg/kg,
      i.p.), an antidepressant, sulpiride (10-25 mg/kg, i.p.), an antipsychotic drug,
      and scopolamine (0.1-1 mg/kg, i.p.), an anticholinergic drug, had no effect. 5.
      Buspirone, a partial 5-HT1A receptor agonist, produced parameter changes similar
      to those induced by anxiolytic benzodiazepines. 8-OH-DPAT, a full 5-HT1A receptor
      agonist, significantly increased transitions and locomotor activity but not %
      time. 5-HT3 receptor antagonists, ICS205-930 and MDL72222, did not have any
      effect on these parameters. 6. Methamphetamine (1-2 mg/kg, i.p.) increased all
      parameters, while caffeine increased only locomotor activity. 7. The present
      findings indicate that the modified light/dark transition test is very simple and
      easy to perform for testing the anxiolytic and anxiogenic effects of drugs.

PMID- 7713362
TI  - Naproxen inhibits hepatic glycogenolysis induced by Ca(2+)-dependent agents.
AB  - 1. The non-steroidal anti-inflammatory naproxen inhibited steady-state
      glycogenolysis stimulation caused by norepinephrine, phenylephrine (alpha 1
      agonists) and methotrexate (not receptor mediated) in the isolated perfused rat
      liver. Stimulation of glycogenolysis caused by these agents is Ca(2+)-dependent.
      2. Naproxen did not inhibit glycogenolysis stimulation caused by glucagon. 3. The
      action of naproxen depended on the extracellular Ca2+ concentration. At 0.25 mM
      extracellular Ca2+, the norepinephrine stimulated glycogenolysis was inhibited by
      60% by 0.5 mM naproxen. At 3.5 mM Ca2+, inhibition was reduced to 25%. The
      inhibition degree correlated linearly with the extracellular Ca2+ concentration.
      4. 45Ca2+ efflux stimulation caused by norepinephrine was not affected by
      naproxen, indicating that the mobilization of the intracellular Ca2+ pools was
      not significantly affected by naproxen. The initial increases in glycogenolysis
      caused by norepinephrine in the absence of extracellular Ca2+ (pre steady-state)
      were not affected by naproxen. These increases depend on intracellular Ca2+
      mobilization. 5. It can be concluded that the action of naproxen is most probably
      related to the cytosolic Ca2+ concentration which, under steady-state conditions,
      depends on the extracellular one during the action of Ca(2+)-dependent
      glycogenolytic agents.

PMID- 7713363
TI  - Effect of nifedipine, verapamil and diltiazem on the enzyme-inducing activity of
      phenobarbital and beta-naphthoflavone.
AB  - 1. The effects of three calcium antagonists (CA), nifedipine (NF), verapamil (V)
      and diltiazem (DL) on the enzyme-inducing activity of phenobarbital (PB) and beta
      naphthoflavone (beta-NF) were measured by hexobarbital (HB) sleeping time,
      benzphetamine-N-demethylase (BND) ethoxycourmarin-O-deethylase (ECOD) and
      ethoxyresorufin-O-deethylase (EROD) activities, as well as by the cytochrome P
      450 and cytochrome b5 content. 2. NF, V and DL at oral doses of 100, 80 and 60
      mg/kg administered 1 hr before PB additionally shortened the HB sleeping time. 3.
      Single administration of calcium antagonists on the background of developed PB
      provoked enzyme induction prolonged the PB-shortened hexobarbital sleeping time.
      4. Three day administration of NF, V and DL plus PB slightly decreased the enzyme
      inducing effect of PB on BND activity and cytochrome P-450 and cytochrome b5
      content. 5. NF and V administered only once after PB-provoked enzyme induction
      increased the PB enzyme-inducing effect on BND activity and on the content of
      cytochrome P-450. DL decreased the PB-induced BND activity and cytochrome P-450
      and cytochrome b5 content. 6. The calcium antagonists studied affected the enzyme
      inducing activity of beta-NF to a lesser extent when compared to PB. Only NF was
      found to potentiate the enzyme-inducing effect of beta-NF on the EROD activity
      and on the cytochrome P-450 content.

PMID- 7713364
TI  - Palytoxin. Recent electrophysiological and pharmacological evidence for several
      mechanisms of action.
AB  - 1. Palytoxin is one of the most potent toxins known so far. It acts as an
      haemolysin and alters the functioning of excitable cells. 2. A primary action of
      palytoxin in excitable cells is to induce the activity of a small conductance (9
      25 pS), non-selective cationic channel which then triggers secondary activations
      of voltage dependent Ca2+ channels and of Na+/Ca2+ exchange. This results in
      neurotransmitter release by nerve terminals and contractions of striated and
      smooth muscle cells. 3. Palytoxin induced channels are blocked by amiloride
      derivatives such as 3,4 dichlorobenzamil. They are also blocked by ouabain but at
      concentrations higher than those required to inhibit the (Na+,K+)ATPase. 4. A
      second and independent action of palytoxin is to open a membrane conductive
      pathway for H+ that drives H+ inside the cells and secondarily activates Na+/H+
      exchange activity. 5. A third action of PTX in chick cardiomyocytes is to raise
      [Ca2+]i in a manner independent of its depolarizing action or of its action on
      intracellular pH. 6. It is suggested that PTX probably has more than one site of
      action in excitable cells and that it may act as an agonist for a family of low
      conductance channels that conduct Na+/K+, H+ and Ca2+ions.

PMID- 7713365
TI  - Difference in excitation-contraction mechanisms between atrial and ventricular
      myocardia of hatched chicks.
AB  - 1. Effects of inotropic interventions on contractile force were examined in
      isolated atrial and ventricular preparations from hatched chicks. 2. The duration
      of twitch contractions were briefer in the atria than in the ventricle. 3. No
      difference in the extracellular Ca(2+)-contractile force curve was observed
      between atrial and ventricular preparations. 4. The sensitivity to nicardipine
      was higher in the ventricular preparations than in atrial preparations while that
      to ryanodine was higher in atrial preparations. 5. The magnitude of post-rest
      contraction was larger than the basal contractile force in atrial preparations,
      while it was smaller than the basal contractile force in ventricular
      preparations. 6. These results suggested that the atrial myocardium of hatched
      chick was more dependent on sarcoplasmic reticulum function than its ventricular
      myocardium, which is similar to the case with mammalian species.

PMID- 7713366
TI  - Effects of YM 435 and A 77636 on dopamine D-1 receptors in bovine retina in
      vitro.
AB  - 1. Homogenates of bovine retinas were used to study the capacities of two new
      dopamine (DA) receptor agonists, e.g. YM 435 and A 77636, to interact with D1
      receptors. 2. Adenylate cyclase experiments. YM 435 and A 77636 enhanced cAMP
      accumulation, with EC50 values of 1.97 microM and 22.9 nM, respectively. The
      receptor-mediated nature of the effects of these two novel D1 agonists was shown
      by the abilities of both SCH 23390 or (+)-butaclamol to inhibit the agonist
      induced increase of cAMP formation. 3. Binding experiments. The same agonists
      were also tested for competition with 3H-SCH 23390 for binding to D1 receptors.
      IC50 values for YM 435 and A 77636 were 8.15 microM and 6.15 nM, respectively. 4.
      The results of the present report demonstrate the suitability of bovine retina in
      vitro to evaluate the specificity of new DA D1 agonists at the receptor level.

PMID- 7713367
TI  - Promotion of sciatic nerve regeneration in rats by a new neurotrophic pyrimidine
      derivative MS-430.
AB  - 1. The effects of a new neurotrophic pyrimidine derivative of MS-430 on nerve
      regeneration was examined using Wistar rats whose left sciatic nerve had been
      subjected to controlled injury. 2. The functional recovery and the packing
      density of common peroneal nerve axons were significantly enhanced with the
      administration of 3 mg/kg/day of MS-430. 3. These results suggest that MS-430 is
      a promising candidate as a neurotrophic drug for clinical use.

PMID- 7713368
TI  - G-proteins in rat blood vessels--I. Identification.
AB  - 1. The purpose of this investigation was to identify various types of
      conventional, low and high molecular weight G-proteins in purified membranes of
      rat aorta and mesenteric artery. 2. In both blood vessels, immunoblotting of G
      proteins using AS/7 antibody specific for Gi-1/2, EC/2 antibody specific for Gi-3
      and RM/1 antibody specific for Gs-type conventional G-proteins demonstrated the
      presence of M(r) 28-43 kDa, M(r) 41 and 48 kDa, and M(r) 36-46 kDa polypeptides,
      respectively. Immunoblotting using a common antibody (GA/1) for the Gs and Gi
      alpha-subunits also revealed the existence of multiple polypeptides (M(r) 24-52
      kDa) in both aorta and mesenteric artery, some of which were identified by the
      specific antibodies. The intensity and number of bands detected by most of the
      antibodies were greater in mesenteric artery than in aorta. 3. Cholera toxin (CT)
      catalyzed ADP-ribosylation of two Gs alpha (M(r) 43, 46 kDa) in both types of
      blood vessels with similar intensities of bands. Pertussis toxin (PT), on the
      other hand, catalyzed ADP-ribosylation of one Gi alpha (M(r) 41 kDa) polypeptide,
      and the intensity of this band was greater in aorta than in mesenteric artery.
      The polypeptides ADP-ribosylated by the toxins corresponded with their
      identification by antibodies. 4. Nitrocellulose blot overlay with [35S]GTP gamma
      S identified at least seven low molecular weight G-proteins (M(r) 21-30 kDa) in
      both aorta and mesenteric artery, with greater intensity of bands in mesenteric
      artery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713369
TI  - G-proteins in rat blood vessels--II. Assessment of functional involvement.
AB  - 1. In this study, we compared G-protein-mediated contractile responses of rat
      aorta and mesenteric artery rings induced by the alpha-adrenoceptor agonist,
      norepinephrine (NE) and by the direct G-protein activator, sodium fluoride, using
      various probes. 2. Activator of the stimulatory G-protein (Gs), cholera toxin
      (CT), attenuated the sensitivity and maximum contractile response of both aorta
      and mesenteric artery to NE and sodium fluoride. The effect of the toxin on the
      NE-sensitivity was greater in mesenteric artery. 3. Pretreatment of tissues with
      the inhibitor of Gi-protein, pertussis toxin (PT), reduced the sensitivity as
      well as maximum contraction of both the aorta and mesenteric artery to sodium
      fluoride, and of the mesenteric artery to NE. PT attenuated only the sensitivity
      but not the maximum contraction of the aorta to NE. The inhibitory effect of PT
      on sensitivity to NE or sodium fluoride was greater in the aorta. 4. NE and
      sodium fluoride-induced contractions were reduced by the sulfhydryl G-protein
      inhibitor, N-ethylmaleimide (NEM) in both blood vessels. NEM produced greater
      inhibitory effect on the sensitivity of the aorta to both contractile agents. 5.
      These data demonstrate that CT, PT and NEM-sensitive G-proteins are involved in
      NE- and sodium fluoride-induced contractile responses of the rat aorta and
      mesenteric artery. The differential effects of the G-protein probes indicate that
      certain variations in G-protein-mediated contractile responses exist among the
      two blood vessels, suggesting that G-protein involvement in functional responses
      may vary with the type of blood vessel investigated.

PMID- 7713370
TI  - Contribution of cyclic GMP generation to the relaxation by nipradilol in the
      rabbit aorta.
AB  - 1. Contribution of cyclic GMP generation to the relaxation by nipradilol of
      vascular smooth muscle was studied in the isolated rabbit aorta contracted by
      phenylephrine (10(-7) M) or prostaglandin F2 alpha (PGF2 alpha, 3 x 10(-6) M). 2.
      Nipradilol-induced relaxation in both contractions and increase in cyclic GMP
      content were inhibited by methylene blue (10(-5) M). 3. The relations between the
      increase in cyclic GMP and the relaxation produced by nipradilol and
      nitroglycerin were fitted to sigmoid curves. The increase in cyclic GMP at 50%
      relaxation by nipradilol was smaller than that by nitroglycerin (1.2-fold
      increase as against 3-fold increase). 4. These results suggest a smaller
      contribution of cyclic GMP generation through activation of soluble guanylate
      cyclase to nipradilol-induced relaxation in the rabbit aorta.

PMID- 7713371
TI  - The effect of indomethacin on cyclosporin A- and its solvent-induced inhibition
      of endothelium-dependent relaxation and the drug-induced contraction of rabbit
      isolated arteries.
AB  - 1. In the isolated rabbit arteries, the effects of intravenous cyclosporin A
      preparation (Sandimmun) and its solvent (Cremophor-EL) on acetylcholine-induced
      endothelium-dependent relaxation were investigated in the absence and presence of
      indomethacin (10(-5) M), a cyclooxygenase inhibitor. 2. The effect of
      indomethacin on the drug- and solvent-induced contraction of superior mesenteric
      artery was also evaluated. 3. The inhibitory effects of cyclosporin and the
      solvent on endothelium-dependent relaxations were decreased by indomethacin. The
      direct contractions produced by the drug and the solvent in rabbit mesenteric
      artery were inhibited by indomethacin.

PMID- 7713372
TI  - Premorbid behaviors produced by cocaine, ethanol and cocaethylene in the mouse.
AB  - 1. The premorbid behaviors produced by the administration of cocaine, ethanol,
      their combination, as well as a metabolite produced by their co-administration,
      viz. cocaethylene, were defined, determined and quantified in the HS strain of
      mice. 2. The LD50 for ethanol was 9.71 g/kg in males and 9.45 g/kg in females,
      whereas the LD50 values in male and female mice for cocaine were 101.55 and 90.00
      mg/kg, respectively. 3. The data indicate that clonic-tonic seizures continued
      into status epilepticus after cocaine administration and prior to cocaine-induced
      lethality. In contrast, administration of the cocaine-ethanol metabolite
      cocaethylene produced status epilepticus without producing clonic-tonic seizures
      yet still resulted in lethality. 4. Thus, both cocaine and cocaethylene may
      produce their lethal effects in mice through neuro-regulatory mechanisms
      mediating protracted seizure induction.

PMID- 7713373
TI  - A turnover study of hypothalamic monoamine oxidase (MAO) and effects of MAO
      inhibition on gonadotropin secretion in the female catfish, Heteropneustes
      fossilis.
AB  - In the present study, the rate constants of degradation (k) and synthesis (S) and
      half-life of hypothalamic monoamine oxidase were determined to explain annual
      variations and biphasic effects of the enzyme to low and high doses of estradiol
      17 beta (E2) in 3-week ovariectomized Heteropneustes fossilis. In the preparatory
      phase, the half-life (t1/2) of the enzyme was the longest (21.16 days) with low k
      (0.03275 days-1) and S (0.000845 Units/day) values, suggesting a low turnover of
      the enzyme. In the prespawning phase the t1/2 was the shortest (11.65 days) with
      high k (0.0595 days-1) and S (0.011 Units/day) values. The low and high turnovers
      of the enzyme, respectively, in these two seasons could be correlated to low and
      high profiles of plasma E2 levels. In the resting phase, the values were in
      between (t1/2 = 18.83 days, k = 0.0368 days-1, S = 0.00211 Units/day) but the
      plasma E2 level was undetectable. Three weeks of ovariectomy increased the t1/2
      (19.04 days) compared to that of the control (11.61 days) with decreases in both
      k and S values. The administration of a low dose of E2 (0.1 micrograms/g BW)
      further increased the t1/2 (19.63 days) over that of the ovariectomized fish with
      a significant rise in the S value. However, a high dose of E2 (1.0 micrograms/g
      BW) decreased it (13.33 days) by reducing the S and elevating the k values. These
      results suggest that the stimulatory effect of low doses of E2 on the enzyme
      activity is produced by elevating its synthesis rate and the inhibitory effect of
      high doses of E2 by simultaneously decreasing the synthesis and increasing the
      degradation rates of the enzyme. The administration of a single dose (75 mg/kg
      BW) of pargyline has elevated plasma gonadotropin (GTH) level after 3 and 6 hr
      and 7 days in the sham-ovariectomized (control), ovariectomized, and
      ovariectomized low-E2-dose groups; the peak increase was found at 6 hr. On the
      contrary, in the ovariectomized high-E2 group the GTH level was inhibited at 3
      and 6 hr postinjection. These changes in the GTH level could be correlated with
      changes in the profiles of hypothalamic monoamines. The data show that E2 exerts
      its feedback regulation of GTH by modifying monoaminergic activity at the level
      of oxidative deamination.

PMID- 7713374
TI  - Cardiovascular actions of frog urotensin II in the frog, Rana catesbeiana.
AB  - The effects of synthetic frog urotensin II on cardiac output and arterial blood
      pressure and on the motility of isolated vascular smooth muscle were investigated
      in the bullfrog, Rana catesbeiana. Bolus injections of frog urotensin II (100
      nmol/kg) into the left systemic arch produced a rapid and sustained fall in blood
      flow through the right branch of the truncus arteriosus (to 62 +/- 5% of
      preinjection values; n = 8). The response exhibited strong tachyphylaxis. There
      were no significant effects on heart rate and central arterial blood pressure but
      the fact that a fall in cardiac output was not accompanied by a fall in pressure
      suggests that the peptide produced an increase in peripheral vascular resistance.
      Rings of vascular smooth muscle from the proximal and distal regions of the left
      and right systemic arches responded to urotensin II with sustained and
      concentration-dependent contractions. The tissues from the different regions did
      not significantly differ in their maximum response and sensitivity to the peptide
      (EC50 values from 4.6 x 10(-9) to 6.5 x 10(-9) M; n = 6). Acetylcholine (3 x 10(
      8) to 3 x 10(-6) M) significantly (P < 0.05) relaxed the rings in an endothelium
      dependent manner but urotensin II did not produce relaxation at any concentration
      tested. The contractile effect of urotensin II (10(-7) M) was not affected by
      preincubation of the rings with atropine, tetrodotoxin, and somatostatin-14 but
      indomethacin produced a significant (P < 0.05) decrease in the amplitude of the
      contractions of the systemic arch (to 18 +/- 2% of control values; n = 6).
      Arachidonic acid (10(-5) M) also produced a sustained contraction of the rings.
      The data suggest an involvement of prostaglandin synthesis in the contractile
      action of urotensin II on isolated frog vascular smooth muscle but, unlike in
      mammals, urotensin II does not stimulate nitric oxide synthesis in this tissue.

PMID- 7713375
TI  - Characterization of the alpha 1B-adrenoceptors of catfish hepatocytes: functional
      and binding studies.
AB  - In catfish hepatocytes (Ictalurus punctatus) alpha 1-adrenergic activation by
      epinephrine or norepinephrine increased cytosol Ca2+ concentration. This effect
      was inhibited by alpha 1-adrenergic antagonists with the potency order WB4101 >
      benoxathian > or = 5-methylurapidil > phentolamine > (+)niguldipine. Pretreatment
      with the irreversible antagonist, chloroethylclonidine, reduced the alpha 1
      adrenergic effect. alpha 1-Adrenergic stimulation also increased the resynthesis
      of phosphatidylinositol in whole cells. In liver membranes, a relatively small
      (33 fmol/mg of protein) number of sites with high affinity (Kd 100 pM) for the
      radioligand [125I]HEAT was detected. Binding competition experiments showed the
      following orders of potency: (1) for agonists, oxymetazoline > epinephrine > or =
      norepinephrine > methoxamine; (2) for antagonists, prazosin > WB4101 >
      benoxathian > or = 5-methylurapidil > phentolamine > (+)niguldipine. Membrane
      pretreatment with chloroethylclonidine markedly reduced [125I]HEAT binding. Good
      correlation was observed between the radioligand binding studies and the
      functional data with isolated cells. The present data suggest that the alpha 1
      adrenoceptor present in catfish liver cells belongs to the alpha 1B subtype.

PMID- 7713376
TI  - Changes in hypothalamic catecholamines, dopamine-beta-hydroxylase, and
      phenylethanolamine-N-methyltransferase in the catfish Heteropneustes fossilis in
      relation to season, raised photoperiod and temperature, ovariectomy, and
      estradiol-17 beta replacement.
AB  - In Heteropneustes fossilis, contents and turnovers of hypothalamic catecholamines
      (CA) and activities of dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N
      methyltransferase (PNMT) showed significant seasonal variations with
      significantly high day values. The seasonal pattern of dopamine (DA) on one hand
      and that of noradrenaline (NA) and adrenaline (A) on the other hand showed an
      inverse relationship, the former decreasing and the latter increasing during the
      progress of gonadal recrudescence. The DBH and PNMT levels were low in the
      resting phase and increased to the peak in the prespawning (DBH) and spawning
      (PNMT) phases. Maintenance of the fish under long photoperiods (16L:8D) and high
      temperature (28 +/- 2 degrees) stimulated the NA and A, and DBH and PNMT
      activities, and suppressed the DA mechanism, the changes being maximal in the
      raised temperature groups. In the resting phase (December), ovariectomy (OVX) or
      estradiol-17 beta (E2) replacement in 4-week ovariectomized fish did not produce
      any significant effects on the CA and enzyme activities. On the contrary, in the
      prespawning phase (May), OVX produced differential and biphasic responses on CA
      and the enzymes. The contents and turnovers of both NA and A increased
      significantly at 2-5 weeks and decreased in the sixth week. However, the reverse
      was true for DA. The DBH and PNMT activities (assayed only 3, 4, and 6 weeks
      after OVX) were elevated significantly in the third and fourth weeks but
      decreased in the sixth week. Plasma levels of gonadotropin (GTH) increased
      significantly at all durations of OVX in a bimodal pattern while the E2 levels
      decreased consistently. Supplementation with a low dose (0.1 microgram/g BW) of
      E2 restored the NA and A and enzyme activities while the higher doses (0.5, 1.0,
      and 5.0 micrograms/g BW) depleted them. The reverse was true for DA. The low dose
      of E2 restored the GTH level while the higher ones inhibited it significantly.
      These results indicate that both environmental photoperiod and temperature and E2
      negative feedback act on the CA to modulate GTH secretion.

PMID- 7713377
TI  - Hypothalamic and thyroidal regulation of growth hormone in tilapia.
AB  - A radioimmunoassay (RIA) for recombinant tilapia growth hormone (GH) was
      established and validated. The ability of various hypothalamic factors to
      regulate GH secretion in the tilapia hybrid (Oreochromis niloticus x Oreochromis
      aureus) was studied. Somatostatin1-14 (SRIF1-14; 10-100 micrograms/kg) was found
      to reduce circulating GH levels in a dose-dependent manner. SRIF1-14 (0.1-1000
      nM) inhibited GH release from perifused pituitary fragments (ED50 0.83 nM). Human
      growth hormone-releasing hormone fragment 1-29 (hGHRH1-29; 100 micrograms/kg)
      doubled circulating GH levels and modestly stimulated GH secretion in vitro. Carp
      growth hormone-releasing hormone (cGHRH) stimulated GH secretion in vitro to a
      similar degree at the same dose (1 microM). Injection of salmon gonadotropin
      releasing hormone (sGnRH) superactive analog (10-100 micrograms/kg) increased
      plasma GH levels sixfold. sGnRH also stimulated GH release in vitro (ED50 142.56
      nM). Dopamine (0.1-10 microM) and the D1 DA receptor agonist SKF 38393 increased
      GH secretion from perifused pituitary fragments dose-relatedly. Thyrotropin
      releasing hormone (TRH) had no effect on GH secretion from perifused pituitary
      fragments, but increased plasma GH levels, as did bovine thyroid stimulating
      hormone (bTSH). The increased plasma GH in the bTSH-treated fish coincided with a
      dramatic increase in T4; however, TRH increased GH without changing T4 levels. T3
      increased the synthesis of GH by isolated pituitaries (incorporation of
      [3H]leucine). SRIF1-14 seems to be a most potent hypothalamic regulator of GH
      secretion in tilapia; sGnRH and DA both increased GH secretion, although sGnRH
      elicited considerably greater responses at lower doses. Two forms of GHRH
      increased GH levels, although the unavailability of the homologous peptide
      prevented an accurate evaluation of its importance in regulating GH secretion.
      The thyroid axis (TRH, TSH, and T3) stimulates both synthesis and release of GH,
      although TRH did not appear to have a direct effect on the level of the
      pituitary.

PMID- 7713378
TI  - A comparison of the responses to gonadotrophin-releasing hormone of adult and
      juvenile, and photosensitive and photorefractory European starlings, Sturnus
      vulgaris.
AB  - The reproductive system of juvenile European starlings appears to be similar to
      that of photorefractory adults, yet the increase in plasma luteinizing hormone
      (LH) in juveniles in response to gonadotrophin-releasing hormone (GnRH) is much
      less than that of photorefractory adults. To investigate this apparent anomaly,
      the effects of age, reproductive state, and sex on the increase in plasma LH
      concentration in response to im injections of GnRH were investigated. The results
      show that photorefractory juveniles needed 10 times the dose of GnRH to elicit
      the same increase in LH as photorefractory adults, and the response of
      photosensitive juveniles to 10 micrograms GnRH was at least 15 times as great as
      that of photorefractory juveniles (e.g., 6.14 micrograms/liter compared to 0.35
      microgram/liter 2 min after injection). However, the response of photosensitive
      adults was not greater than that of photorefractory adults. These differences
      were not due to differences in the amount of LH stored in the pituitary: this was
      298 +/- 34 and 306 +/- 51 ng/gland in photorefractory juveniles and adults,
      respectively, and 367 +/- 47 in photosensitive juveniles. Repeated weekly
      treatment with GnRH enhanced LH responses: LH levels 3 min after GnRH treatment
      increased in birds on short days from 7.7 micrograms/liter after the first
      treatment to 24.6 micrograms/liter after the sixth treatment and in birds on long
      days it increased from 0.54 to 1.8 micrograms/liter. The greater response of
      photorefractory adults compared to photorefractory juveniles may therefore be due
      to the self-priming effect of GnRH during a preceding period of photosensitivity
      and/or photostimulation. The response to exogenous GnRH depends more on age and
      history than on prevailing physiological state. There was also a marked sex
      difference: females showed a sevenfold greater response to GnRH.

PMID- 7713379
TI  - Absence of a tiGH effect on adaptability to brackish water in tilapia
      (Oreochromis niloticus).
AB  - The aim of this study was to investigate the possible role of growth hormone in
      the adaptation of tilapia (Oreochromis niloticus) to brackish water and to
      analyze its interactions with prolactin in this process. Plasma levels of growth
      hormone do not change upon transfer to brackish water. Treatment of intact
      tilapia in fresh water with growth hormone prior to transfer did not enable the
      fish to preadapt to brackish water: the duration of the hydromineral imbalance
      after transfer was the same in treated animals and controls. The major
      osmoregulatory role of prolactin in fresh water led us to test the hypothesis
      that prolactin might antagonize the effect of growth hormone on adaptation to
      brackish water. Growth-hormone-treated hypophysectomized animals, however,
      exhibited no increased osmoregulatory capacity as compared to hypophysectomized
      controls, confirming the absence of a growth-hormone-related osmoregulatory
      effect. When prolactin and growth hormone were coinjected, growth hormone also
      proved unable to oppose the Na+ retaining effect of prolactin, in both brackish
      and fresh water. Surprisingly, hypophysectomized animals adapt better to brackish
      water than do sham-operated animals. This result is discussed in light of the
      effects of prolactin and cortisol on osmoregulation in brackish water and we
      suggest that an important event which allows O. niloticus to adapt to
      hyperosmotic environment is the reduction of plasma PRL upon transfer to brackish
      water.

PMID- 7713380
TI  - Dopaminergic and enkephalinergic involvement in the regulation of blood glucose
      in the red swamp crayfish, Procambarus clarkii.
AB  - In in vivo experiments injection of dopamine (DA) or leucine enkephalin (L-Enk)
      produced hypoglycemia in intact red swamp crayfish, Procambarus clarkii. In
      contrast, neither compound had a significant effect on the circulating glucose
      concentration in eyestalkless individuals. With intact crayfish spiperone, a DA
      receptor blocker, inhibited this hypoglycemic action of DA but not this action of
      L-Enk. In contrast, in intact crayfish naloxone, a competitive opioid antagonist,
      inhibited the in vivo hypoglycemic actions of both L-Enk and DA. In vitro, both
      DA and L-Enk reduced the rate of release of the crustacean hyperglycemic hormone
      (CHH) from isolated eyestalk neuroendocrine tissue. These results suggest that
      both DA and L-Enk act to inhibit release of CHH by affecting the eyestalk
      neuroendocrine complex and that the enkephalinergic inhibitory neuron follows the
      dopaminergic inhibitory neuron in the chain of neurons which leads to the
      neuroendocrine cells that secrete CHH.

PMID- 7713381
TI  - Newly hatched chick ovarian cell subpopulations metabolize distinctively
      progestin and androgen precursors.
AB  - The aim of this study was to characterize the ability of four different cell
      fractions (F1, F2, F3, and F4), isolated from the ovary of newly hatched chick by
      means of subsequent metrizamide gradients (0-15%), to metabolize progestins and
      androgens. The results showed the presence of 17 alpha-hydroxylase/C17-20 lyase
      and 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) activities in the
      typical steroidogenic cells isolated in F1 (d = 1.012 g/ml). Primary oocytes
      present in F2 (d = 1.037 g/ml) did not show relevant steroid metabolism in the
      various assays that were carried out. Fractions 3 (d = 1.055 g/ml) and 4 (d =
      1.071 g/ml), which contained a mixture of prefollicular and poorly differentiated
      epithelial cells, presented both 5 beta-reductase and aromatase activities,
      whereas 17 beta-HSD activity was mainly located in the cells of fraction 3. It is
      highly possible that poorly differentiated epithelial cells of fractions 3 and 4
      are responsible for the steroidogenic activity. We conclude that in newly hatched
      chick ovary, typical steroidogenic cells metabolize progestins to androgens, and
      poorly differentiated epithelial cells further aromatize androgens to estrogens.
      In addition, we suggest the existence of at least two metabolically distinct
      poorly differentiated epithelial cell subpopulations, one presenting 5 beta
      reductase and aromatase activities and another exhibiting 17 beta-HSD activity.

PMID- 7713382
TI  - The effects of calcitonin on serum calcium levels in immature brown trout, Salmo
      trutta.
AB  - Salmon calcitonin was administered intraperitoneally (0.1, 10, 1000 ng/100 g of
      fish) to freshwater-adapted, immature, female brown trout, Salmo trutta, and
      changes in serum calcium levels were determined. The lowest dose (0.1 ng) had an
      effect similar to injection of saline (control), but the higher doses produced
      hypercalcemia. These latter effects were associated with increased serum levels
      of calcitonin. Maintaining immature brown trout in waters containing 20 and 50 mM
      calcium chloride resulted in a significant lowering of serum calcitonin with time
      although serum calcium levels remained stable. The extent of the decrease in
      serum calcitonin increased with the higher levels of environmental calcium.

PMID- 7713384
TI  - Ontogeny of the cortisol stress response in larval rainbow trout.
AB  - The ontogeny of the interrenal stress response in rainbow trout was characterized
      by measuring resting and acute-stress-induced changes in whole-body cortisol
      levels in embryos and larvae at different early developmental stages. In
      Experiment 1, resting cortisol levels averaged 6.0 ng/g in newly fertilized eggs,
      fell to less than 0.3 ng/g by the time of hatching at Week 4 (incubation at 10
      degrees), and increased to 1.4 ng/g by Week 5. Cortisol levels did not change in
      response to acute stress in 3-, 4-, or 5-week-old fish. In Experiment 2, resting
      cortisol averaged 1.4 ng/g in newly fertilized eggs, fell to less than 0.03 ng/g
      by Week 2, and then steadily increased between Weeks 3 and 6 to a peak of 4.8
      ng/g before falling to 1.2 ng/g by Week 7. Cortisol levels did not change in
      response to acute stress in 3-, 4-, or 5-week-old fish. Six-week-old fish showed
      a 2.3-fold increase in cortisol levels at 1 hr poststress, indicating that the
      hypothalamic-pituitary-interrenal axis first develops responsiveness to stress 2
      weeks after hatching and 1 week before the onset of exogenous feeding. The stress
      hyporesponsive period after hatching in rainbow trout may be homologous to the 2
      week stress hyporesponsive period after birth in rodents, the function of which
      may be to maintain low, constant corticosteroid levels during a critical
      developmental period when these steroids can have permanent effects on neural
      organization. As suggested for mammals, this period may be a time when rainbow
      trout are particularly vulnerable to environmental effects on their subsequent
      development.

PMID- 7713385
TI  - Seasonal changes in thyroid activity in male and female frog, Rana perezi.
AB  - Plasma T3 and T4 levels, and thyroid free (f) and bound (b) thyroid hormones
      contents, were determined by radioimmunoassay in adult male and female Rana
      perezi over 1 year. Plasma T3 levels show a significant seasonal cycle in both
      male and female frogs, increasing from January to peak in July (71-74 pg/ml) to
      decrease in August-October. Plasma T4 concentrations also varied seasonally, and
      sex differences were apparent. Basal T4 levels from the end of summer to the end
      of winter and higher values (682-651 pg/ml) in spring and early summer occur in
      female frogs; males have lowest levels in October (59.78 +/- 13.92 pg/ml) and
      higher levels during the rest of the year, except for a significant decrease in
      April. The thyroid content of fT3 and fT4 displayed similar seasonal patterns,
      with peak values in April and July-August. Sex differences are again present. The
      thyroid contents of bT3 are high between March and July in both sexes, with
      values in females being greater than those in males. The bT4 content follows a
      similar seasonal pattern in males and females and shows a minimum in March and a
      maximum in summer. Thyroid releasing capacity seems to change depending on the
      season and sex.

PMID- 7713383
TI  - Inhibition of adrenal steroidogenesis, neonatal feed restriction, and pituitary
      adrenal axis response to subsequent fasting in chickens.
AB  - White Plymouth Rock chickens placed under 60% feed restriction or ad libitum
      feeding, with or without metyrapone (adrenal blocking agent) treatment, from 4 to
      6 days of age were subjected to either 8 or 24 hr feed deprivation at 36 days of
      age. Chicks subjected to the neonatal 60% feed restriction (60R) but not those
      provided metyrapone during the procedure (60M) had elevated heterophil/lymphocyte
      (H/L) ratios. However, there was no difference in plasma corticosterone and ACTH
      responses between 60R and 60M chicks. Except for increases in H/L and plasma
      corticosterone concentrations among ad libitum fed (AL) and 60M chickens,
      respectively, there was no indication of stress response attributable to the
      subsequent 8 hr fast. Feed withdrawal for 24 h did not cause rises in H/L ratios
      and plasma levels of corticosterone of chicks that had been subjected to early
      60% feed restriction with nonmetyrapone-treated feed. In contrast, chicks of
      other regimens had elevated H/L and plasma corticosterone responses when exposed
      to a similar procedure. Except for those fed ad libitum during the neonatal
      stage, circulating levels of ACTH declined following the 24-hr fast. These
      results demonstrate that stress early in life without concurrent rises in
      circulating corticosteroid levels may not help the biological system in coping
      with subsequent stressors.

PMID- 7713386
TI  - What are the origins of ecdysteroids in gastropods?
AB  - Terrestrial gastropods contain ecdysteroids, the origins of which are unknown.
      Whether they are synthesized by the animals or they arise from the diet is an
      open question. To address this problem, labeled cholesterol and various molecules
      which are efficiently converted into ecdysone by arthropods were tested as
      possible ecdysone precursors in Stylommatophra (gastropods). None of these
      experiments led to ecdysone biosynthesis and although snails and slugs were shown
      to contain some of the enzymes required for a biosynthetic pathway (i.e., a 3
      oxoecdysteroid 3 beta-reductase, a 25-hydroxylase, and a 20-hydroxylase), no 2
      hydroxylase and 22-hydroxylase activity could be detected. An endogenous origin
      would imply that Stylommatophora use a biosynthetic pathway different from that
      of insects. A dietary origin for ecdysteroids is also possible since, when
      ingested, these molecules remain in animals for several days and undergo limited
      metabolic conversion.

PMID- 7713387
TI  - Influence of androgens on differentiation of secondary sex characters in tree
      lizards, Urosaurus ornatus.
AB  - Vertebrates species vary in the degree to which the sexes differ in their
      expression of secondary sex characters, which can be expressed in one sex but not
      the other, fully expressed in both sexes, or expressed to different degrees in
      the two sexes. Sex steroid hormones contribute to the development of sex
      differences, either through action early in life (organization), following sexual
      maturation (activation), or both. However, relatively little is known about the
      contributions of sex steroid hormones to species-level variation in sexual
      dimorphism. We began to address this by assessing in tree lizards, Urosaurus
      ornatus, the effects of testosterone (T) and dihydrotestosterone (DHT) on
      expression of the male-typical traits: femoral pore secretions, accessory sex
      tissues, patches of ventrolateral blue, intensity and hue of throat color, and
      body size. We administered long-lasting hormone implants of these androgens to
      intact or ovariectomized adult females, intact hatchling females, and intact
      hatchling males to determine the relative contribution of organizational and
      activational influences of androgens on sexual differentiation of these traits.
      Waxy femoral pore secretions and full intensity of the orange background color of
      the throat fan (dewlap) required only activation and both androgens were equally
      effective. Both androgens caused hypertrophy of accessory tissues associated with
      the hemipenes, but only in hatchling males. Full expression of ventrolateral blue
      patches required organization by DHT. Androgens had complex organizational
      actions on growth. In the doses used in the experiment, DHT inhibited body-length
      growth but not mass growth of hatchling males. Only T inhibited the growth
      (length and mass) of hatchling females. Because earlier work found that
      castration also reduced the growth of hatchling males, the organizational effects
      of androgen on growth might be dose-related. Results for hormonal control of
      dewlap type were complex. In this population dewlap color is solid orange in
      females, but polymorphic in males with 50% expressing solid orange (O) and 50%
      orange-blue (orange with a central blue patch, OB). These color morphs represent
      permanent male alternatives: OB males are territorial and more aggressive than O
      males who do not defend territories. Results of the hormone manipulations are
      most consistent with the interpretation that dewlap morph type requires both
      organization and activation by androgen. T appears to be more important in
      organizing morph differences, whereas DHT appears to be more important in
      activating expression of underlying morph differences. Females only expressed
      male-typical OB dewlaps when given DHT, and only about 50% did so.

PMID- 7713388
TI  - Direction of causation models.

PMID- 7713389
TI  - Direction of causality.

PMID- 7713390
TI  - Appropriate questions about causal inference from "Direction of Causation"
      analyses.

PMID- 7713391
TI  - Inferring the direction of causation in cross-sectional twin data: theoretical
      and empirical considerations.
AB  - A recent multivariate extension of the classical twin study in theory allows the
      inference of the direction of causation between correlated traits solely using
      cross-sectional data. In this paper we briefly review this model and assess its
      usefulness by applying it to a number of pairs of biological and psychological
      variables between which the nature of the causative relationship is already
      known. We conclude that the method has a number of biases and limitations. If a
      causative relationship at the phenotypic level exists between two traits, the
      correct direction of causation is usually identifiable, providing the reliability
      and validity of the measures are known. Failure to correctly specify a
      measurement model can lead to incorrect tests of hypotheses. Difficulties can
      also occur when discriminating between a direct causative relationship and a
      correlation due to common genetic or environmental determinants, but these occur
      in predictable situations. If these considerations are taken into account in
      interpretation of results, the true nature of the association between traits can
      often be correctly identified, or at least included in a subgroup of best fitting
      models.

PMID- 7713392
TI  - Depression and parental bonding: cause, consequence, or genetic covariance?
AB  - It is shown how information on the direction of causation between variables may
      be obtained from a cross-sectional study of pairs of relatives. This method is
      applied to the study of the relationship between ratings of parents' rearing
      style and depression in their offspring. Adult female twins ascertained from a
      population-based registry in Viroffia completed the Center for Epidemiological
      Studies--Depression Scale (CESD) and a 7-item short form of the Parental Bonding
      Instrument (PBI) about each of their parents. Two dimensions of parental
      behavior, overprotectiveness and coldness, were analyzed jointly with depression
      data in both genetic factor and directional genetic models. Models that specify
      ratings of parents as a cause of depression in the offspring fit the data
      significantly better than models that specify depression as a cause of ratings of
      parents. A still better fit is obtained with models that specify common genetic
      variance to depression and ratings, though causal models with error variance
      perform almost as well. In general, ratings of fathers show more genetic and less
      shared environmental variance than ratings of mothers, which might arise from
      more consistent treatment of offspring by mothers than by fathers. No effect of
      children eliciting parental rearing style was detected with these data. The
      relative merits of instrumental variable, longitudinal, and family approaches to
      testing causal models are discussed.

PMID- 7713393
TI  - Feasibility of half-sibling designs for detecting a genetic component to a
      disease.
AB  - In genetic epidemiology, adoption and twin study designs are the most commonly
      used designs to identify genetic and common environmental components underlying
      familial aggregation. Other fixed family set designs such as a half-sibling
      design can also be applied to test the same hypothesis. The feasibility of half
      sibling designs for detecting a genetic (single-locus or multifactorial) source
      of familial aggregation of a disease is studied and is compared to both adoption
      and twin study designs. Results are presented for two types of design when the
      sampling units are relative pairs reared apart (I) or reared together (II).
      Although they generally require more observations to achieve the same power,
      designs involving half-siblings may be more feasible in situations where there is
      greater availability of these relatives.

PMID- 7713394
TI  - Interaction between genetic and environmental risk factors for Alzheimer's
      disease: a reanalysis of case-control studies.
AB  - To study the interaction among genetic and environmental risk factors, a
      reanalysis of case-control studies of Alzheimer's disease (AD) was conducted
      based on the original data of all studies carried out to January 1, 1990. Seven
      studies were included in the present analysis, comprising a total of 814 AD
      patients and 894 control subjects. When comparing those with a positive and
      negative family history of dementia, similar odds ratio were found for late
      maternal age [1.7; 95% confidence interval (0.6-4.8) vs. 2.0 (1.1-3.5)], head
      trauma [1.7 (0.7-4.2) vs. 1.9 (1.1-3.2)], and history of depression [2.0 (0.2
      19.8) vs. 2.1 (0.8-1.7)]. This suggests a model in which these risk factors
      increase the risk for AD independent of family history of dementia. Among those
      with a positive family history of dementia, the odds ratios for family history of
      Down's syndrome [4.2 (0.9-20.0)] and of Parkinson's disease [3.3 (0.4-28.2)]
      tended to be higher than among those with a negative family history of dementia
      [2.6 (0.8-8.5) and 2.4 (0.8-7.0), respectively]. However, for both disorders the
      difference in odds ratio was not statistically significant. For history of
      cigarette smoking, there was no association to AD for those with no first degree
      relatives with dementia and an inverse relation with AD for those with a positive
      family history. Although in all analyses, family history of dementia remained
      significantly associated with AD in the absence of other factors, the odds ratio
      associated with family history of dementia tended to be lower for those with a
      positive smoking history, particularly for those with two or more affected
      relatives. These findings suggest that smoking may interact specifically with a
      genetically determined process.

PMID- 7713395
TI  - Evidence for multiple genes determining sodium transport.
AB  - Sodium transport comprises a set of interacting systems. Consequently, a
      defective sodium transport gene affects multiple sodium transport systems, and a
      sodium transport variable measured on a sample of individuals reflects genetic
      variation from a number of different genes, complicating the task of identifying
      the effect of a single gene. To test for genes which affect sodium transport, we
      first applied principal components analysis to 14 variables related to sodium
      transport, thereby defining uncorrelated sources of variation in the variables.
      The sample consisted of 1,218 members of 68 pedigrees ascertained through
      probands with early-onset stroke, hypertension, or coronary heart disease.
      Segregation analysis of the 14 principal components scores provided evidence for
      8 genetic variants which alter sodium transport. One of the 8 variants is
      recessive, has homozygous genotype frequency estimated as 8.8% of the population,
      and increases sodium-lithium countertransport, the passive sodium leak, body mass
      index, and triglyceride; the genetic variant may coincide with an insulin
      resistance gene. A second of the 8 variants is also recessive, has homozygous
      genotype frequency estimated as 7.4% of the population, and increases
      intraerythrocytic sodium and the passive sodium leak while decreasing sodium pump
      number; the genetic variant may reduce pump number. Two of the 8 variants
      substantially increase sodium-lithium countertransport; frequency estimates for
      heterozygotes for the dominant variant and homozygotes for the recessive variant
      equal 1.8% and 3.1%, respectively. Another of the 8 variants is recessive, has
      homozygous genotype frequency estimated as 1.9%, and increases body mass index.
      Each of the 3 remaining variants is rare and expressed in less than 1% of the
      sample.

PMID- 7713396
TI  - Segregation analysis of human red blood cell thiopurine methyltransferase
      activity.
AB  - Thiopurine methyltransferase (TPMT) catalyzes thiopurine S-methylation, an
      important metabolic pathway for drugs such as 6-mercaptopurine (6-MP). Inherited
      differences in the activity of this enzyme are related to individual differences
      in the therapeutic efficacy and toxicity of 6-MP and other thiopurine drugs.
      Variation of TPMT activity in the red blood cell (RBC) has been found to reflect
      activity differences in less accessible tissues. Previously reported qualitative
      analyses of inheritance of RBC TPMT in families suggested that a major gene plays
      a role in the regulation of activity of this enzyme. In the present study we
      completed complex segregation analyses of RBC TPMT activity of 213 individuals in
      49 families that were randomly ascertained through children in the Rochester, MN,
      public school system. We found clear evidence of a major gene effect on RBC TPMT
      activity. Both transformed and untransformed data supported the segregation of a
      Mendelian major gene with frequency of 0.94 for the allele conferring high enzyme
      activity. The genotype distributions of individuals who were homozygous for the
      low activity allele, heterozygous, and homozygous for the high activity allele
      accounted for approximately 0.3%, 11.2%, and 88.5%, respectively, of the
      individuals in the sample. This major locus accounted for 66% of the total
      variance in untransformed RBC TPMT activity. Although there were significant
      residual family correlations among probable high activity homozygotes, there was
      insufficient power to detect additional major locus or polygenic inheritance
      effects on the residual variance.

PMID- 7713397
TI  - ARCAD: a method for estimating age-dependent disease risk associated with
      mutation carrier status from family data.
AB  - We present ARCAD, a method to estimate the disease risk associated with mutation
      carrier status using data on families ascertained by affected individuals, in
      which a germline mutation has been detected. Because the event of interest, the
      age of onset, is a censored variable, the method uses the survival analysis
      approach to formulate the likelihood. Provided that selection criteria are
      clearly defined, the ascertainment bias is removed by including a correction term
      in the likelihood computation. We simulated family data and selected those with a
      proband affected before age 17, and at least one or at least two relatives
      affected before age 46. We show that including the correction for the
      ascertainment provides reliable estimates of the risk, even when many individuals
      are not tested for the mutation. An application to cancer risk and germline p53
      mutations is presented. We routinely investigate the p53 status for all the
      children treated in the Department of Pediatric Oncology at the Institute Gustave
      Roussy, whose family displays at least one relative affected by cancer before age
      46. We identified 5 families with an inherited germline p53 mutation. The risk
      for any cancer for a mutation carrier estimated by ARCAD was 42% within the age
      class 0-16 years, 38% within the age class 17-45 years, and 63% after 45 years,
      with a lifetime risk of 85%. These risks are almost entirely explained by the
      occurrence of the six most frequent cancers encountered in the Li-Fraumeni
      syndrome.

PMID- 7713398
TI  - Comparison of analysis of variance and maximum likelihood based path analysis of
      twin data: partitioning genetic and environmental sources of covariance.
AB  - In order to investigate currently used model fitting strategies for twin data,
      analysis of variance (ANOVA) and path-maximum-likelihood (PATH-ML) methods of
      analyzing twin data were compared using simulation studies of 50 monozygotic (MZ)
      and 50 dizygotic (DZ) twin pairs. Phenotypic covariance was partitioned into
      additive genetic effects (A), environmental effects common to cotwins (C), and
      environmental variance unique to individuals (E). ANOVA and PATH-ML had identical
      power to detect total covariance. The PATH-ML AE model was much more powerful
      than ANOVA comparisons of rMZ and rDZ to detect A. However, to be unbiased, the
      AE model requires the assumption that C = 0.0. To allow use of the AE model to
      estimate A, the null hypothesis C = 0.0 is tested by comparing the goodness of
      fit of the ACE and AE models. Simulation of 50 MZ and 50 DZ pairs revealed that C
      must be greater than 55% of total variance before the null hypothesis would be
      rejected (P < 0.05) 80% of the time. Several recent publications were reviewed in
      which the null hypothesis C = 0.0 was accepted and apparently upwardly biased
      estimates of A, containing C, were presented with unrealistic P values. It was
      concluded that use of the AE model to estimate A gives an inflated view of the
      power of relatively small twin studies. It was recommended that ANOVA or
      comparison of the ACE and CE PATH-ML models be used to estimate and test the
      significance of A as neither requires that C = 0.0.

PMID- 7713399
TI  - Epidemiology of retinitis pigmentosa in the Valencian community (Spain).
AB  - The purposes of this study are to determine the frequencies of the different
      genetic forms of retinitis pigmentosa and to perform segregation analysis in the
      different genetic subtypes. Retinitis pigmentosa was diagnosed in 263 persons
      from 132 families. The frequency of the autosomal recessive type was the highest
      (31.8%) while the X-linked type was very rare (1.5%). The frequency of autosomal
      dominant type was 14.4% and the simplex cases constituted half of the total cases
      of RP registered in our community. In conclusion, in our population the high
      proportion of simplex cases and the low number of X-linked families are
      noticeable. The result of segregation analysis showed good agreement with
      expectation in autosomal dominant and autosomal recessive families but no more
      than 60% of all simplex cases were autosomal recessive. The proportion of
      sporadic cases was estimated statistically to be 39.9% of the total simplex
      cases.

PMID- 7713400
TI  - Extended HLA profile of an inbred isolate: the Schmiedeleut Hutterites of South
      Dakota.
AB  - HLA-A, -B, -C, -DR, and -DQ typings of the Schmiedeleut Hutterites of South
      Dakota were collected as part of an ongoing genetic-epidemiologic study of HLA
      and fertility. A total of 1,082 individuals, including 852 married adults
      representative of the reproductive population of this isolate, were characterized
      for five-locus HLA haplotypes. HLA-A1, A2, A3, and A24 accounted for 75% of
      observed HLA-A alleles and HLA-B27, B35, B51, and B62 accounted for 55% of
      observed HLA-B alleles. S-leut Hutterites are derived from 68 or fewer ancestors.
      However, only 48 ancestral HLA haplotypes were observed and nine of these
      accounted for over 52% of the observed haplotypes. Measures of two-locus linkage
      disequilibrium derived from these haplotypes indicated that one-third to half of
      the observed HLA-A/B, B/DR, and A/DR allele combinations exhibited highly
      statistically significant linkage disequilibrium. Allele and haplotype
      frequencies did not differ between males and females. Recombination rates of
      0.004% and 0.005% between HLA-A and -C and between HLA-B and -DR, respectively,
      were observed. This HLA profile points out a paucity of HLA alleles and
      haplotypes in this population and marked linkage disequilibrium among the HLA
      alleles that are present.

PMID- 7713402
TI  - Apolipoprotein E4 allele and Alzheimer disease: examination of allelic
      association and effect on age at onset in both early- and late-onset cases.
AB  - An increased frequency of the apolipoprotein E type 4 allele (APOE-4) has
      previously been associated with both late-onset sporadic and late-onset familial
      Alzheimer disease (AD) [Strittmatter et al. (1993) Proc Natl Acad Sci USA 90:1977
      1981; Saunders et al. (1993a) Neurology 43:1467-1472]. To further investigate
      this association we genotyped affected individuals from 92 separate AD pedigrees
      including both early- and late-onset cases. An increased frequency of the APOE-4
      allele was found only among the late-onset cases, both familial and sporadic,
      confirming the earlier reports. In addition, age at onset was significantly
      decreased in the APOE-4 homozygotes (in late onset families) compared to either
      APOE-4 heterozygotes or individuals not carrying an APOE-4 allele. We also
      observed a significantly decreased frequency of the APOE-2 allele in both the
      early- and late-onset familial cases. These results strengthen the argument for a
      direct role of APOE in susceptibility to AD.

PMID- 7713401
TI  - Complex segregation analysis of leprosy in southern Vietnam.
AB  - To investigate the nature of the genetic component controlling susceptibility to
      leprosy and its subtypes, 402 nuclear families were ascertained through a leprosy
      patient followed at the Dermatology Hospital in Ho Chi Minh City, Vietnam; 285
      families were of Vietnamese origin and 117 were of Chinese origin with a higher
      proportion of lepromatous forms among Chinese patients. Segregation analyses were
      conducted using the model developed by Abel and Bonney [(1990) Genet Epidemiol
      7:391-407], which accounted for variable age of onset and time-dependent
      covariates. Three phenotypes were considered: leprosy per se (all forms of
      leprosy together), nonlepromatous leprosy, and lepromatous leprosy. For each of
      this phenotype, analyses were performed on the whole sample and separately on the
      Vietnamese and the Chinese families. The results showed that a single Mendelian
      gene could not account for the familial distributions of leprosy per se and its
      two subtypes in the whole sample. However, these results were different according
      to the ethnic origin of the families. In the Vietnamese subsample, there was
      evidence for a codominant major gene with residual familial dependences for the
      leprosy per se phenotype, and borderline rejection of the Mendelian transmission
      hypothesis for the nonlepromatous phenotype. In Chinese families, strong
      rejection of Mendelian transmission was obtained in the analysis of leprosy per
      se, and no evidence for a familial component in the distribution of the
      nonlepromatous phenotype was observed. For the lepromatous phenotype, the
      discrimination between models was poor, and no definitive conclusion could be
      reached. Referring to immunological data, we suggest that these results could be
      explained by a heterogeneity in the definition of the lepromatous phenotype. It
      is likely that progress in the understanding of the genetic components involved
      in the expression of leprosy will come from a better definition of the phenotype
      under study, and immunological studies are ongoing in this population to
      investigate this hypothesis.

PMID- 7713403
TI  - Detection of a recessive major gene for high IgE levels acting independently of
      specific response to allergens.
AB  - The genetic control of the total IgE, the immunoglobulins E involved in allergy,
      remains still unclear. Although high IgE levels were found to be determined by a
      recessive major gene in several studies, other modes of inheritance were also
      reported. Moreover, at least two different genetic mechanisms controlling the IgE
      regulation have been suggested: one involved in the specific IgE response and the
      other one in the nonspecific response. To better understand the genetic
      mechanisms controlling IgE variation, we performed segregation analysis of IgE
      levels by ignoring or taking into account the specific response to allergens
      (SRA). Analyses were conducted using the class D regressive model, in a sample of
      234 Australian nuclear families randomly selected during the winter months, when
      IgE levels are the lowest (basal). SRA, when included as a covariate in the
      model, was defined by one of the three following criteria: (1) raised specific
      IgE level for one or more allergens, (2) positive skin test for one or more
      allergens, and (3) at least one of the (1) or (2) criteria. When the presence of
      SRA is ignored, the familial transmission of total IgE level is compatible with
      the segregation of a recessive major gene and residual familial correlations.
      When the presence of SRA is accounted for in the analysis, whether defined by
      criteria (1), (2), or (3), there is still evidence for a recessive major gene
      controlling IgE levels but residual familial correlations are no longer
      significant. In addition, no interaction between this major gene and SRA is shown
      here. Our results suggest that this gene, which accounts for 28% of the variation
      of the trait, may be involved in the control of basal IgE production,
      independently of specific response to allergens.

PMID- 7713404
TI  - On the effective size of populations with separate sexes, with particular
      reference to sex-linked genes.
AB  - Inconsistencies between equations for the effective population size of
      populations with separate sexes obtained by two different approaches are
      explained. One approach, which is the most common in the literature, is based on
      the assumption that the sex of the progeny cannot be identified. The second
      approach incorporates identification of the sexes of both parents and offspring.
      The approaches lead to identical expressions for effective size under some
      situations, such as Poisson distributions of offspring numbers. In general,
      however, the first approach gives incorrect answers, which become particularly
      severe for sex-linked genes, because then only numbers of daughters of males are
      relevant. Predictions of the effective size for sex-linked genes are illustrated
      for different systems of mating.

PMID- 7713405
TI  - Effective size of populations under selection.
AB  - Equations to approximate the effective size (Ne) of populations under continued
      selection are obtained that include the possibility of partial full-sib mating
      and other systems such as assortative mating. The general equation for the case
      of equal number of sexes and constant number of breeding individuals (N) is Ne =
      4N/[2(1 - alpha I) + (Sk2 + 4Q2C2) (1 + alpha I + 2 alpha O)], where Sk2 is the
      variance of family size due to sampling without selection, C2 is the variance of
      selective advantages among families (the squared coefficient of variation of the
      expected number of offspring per family), alpha I is the deviation from Hardy
      Weinberg proportions, alpha O is the correlation between genes of male and female
      parents, and Q2 is the term accounting for the cumulative effect of selection on
      an inherited trait. This is obtained as Q = 2/[2 - G(1 + r)], where G is the
      remaining proportion of genetic variance in selected individuals and r is the
      correlation of the expected selective values of male and female parents. The
      method is also extended to the general case of different numbers of male and
      female parents. The predictive value of the formulae is tested under a model of
      truncation selection with the infinitesimal model of gene effects, where C2 and G
      are a function of the selection intensity, the heritability and the intraclass
      correlation of sibs. Under random mating r = alpha I = -1/(N - 1) and alpha O =
      0. Under partial full-sib mating with an average proportion beta of full-sib
      matings per generation, r approximately beta and alpha O approximately alpha I
      approximately beta/(4 - 3 beta). The prediction equation is compared to other
      approximations based on the long-term contributions of ancestors to descendants.
      Finally, based on the approach followed, a system of mating (compensatory mating)
      is proposed to reduce rates of inbreeding without loss of response in selection
      programs in which selected individuals from the largest families are mated to
      those from the smallest families.

PMID- 7713406
TI  - Modeling interference in genetic recombination.
AB  - In analyzing genetic linkage data it is common to assume that the locations of
      crossovers along a chromosome follow a Poisson process, whereas it has long been
      known that this assumption does not fit the data. In many organisms it appears
      that the presence of a crossover inhibits the formation of another nearby, a
      phenomenon known as "interference." We discuss several point process models for
      recombination that incorporate position interference but assume no chromatid
      interference. Using stochastic simulation, we are able to fit the models to a
      multilocus Drosophila dataset by the method of maximum likelihood. We find that
      some biologically inspired point process models incorporating one or two
      additional parameters provide a dramatically better fit to the data than the
      usual "no-interference" Poisson model.

PMID- 7713408
TI  - Statistical analysis of chromatid interference.
AB  - The nonrandom occurrence of crossovers along a single strand during meiosis can
      be caused by either chromatid interference, crossover interference or both.
      Although crossover interference has been consistently observed in almost all
      organisms since the time of the first linkage studies, chromatid interference has
      not been as thoroughly discussed in the literature, and the evidence provided for
      it is inconsistent. In this paper with virtually no restrictions on the nature of
      crossover interference, we describe the constraints that follow from the
      assumption of no chromatid interference for single spore data. These constraints
      are necessary consequences of the assumption of no chromatid interference, but
      their satisfaction is not sufficient to guarantee no chromatid interference.
      Models can be constructed in which chromatid interference clearly exists but is
      not detectable with single spore data. We then extend our analysis to cover
      tetrad data, which permits more powerful tests of no chromatid interference. We
      note that the traditional test of no chromatid interference based on tetrad data
      does not make full use of the information provided by the data, and we offer a
      statistical procedure for testing the no chromatid interference constraints that
      does make full use of the data. The procedure is then applied to data from
      several organisms. Although no strong evidence of chromatid interference is
      found, we do observe an excess of two-strand double recombinations, i.e.,
      negative chromatid interference.

PMID- 7713407
TI  - Statistical analysis of crossover interference using the chi-square model.
AB  - The chi-square model (also known as the gamma model with integer shape parameter)
      for the occurrence of crossovers along a chromosome was first proposed in the
      1940's as a description of interference that was mathematically tractable but
      without biological basis. Recently, the chi-square model has been reintroduced
      into the literature from a biological perspective. It arises as a result of
      certain hypothesized constraints on the resolution of randomly distributed
      crossover intermediates. In this paper under the assumption of no chromatid
      interference, the probability for any single spore or tetrad joint recombination
      pattern is derived under the chi-square model. The method of maximum likelihood
      is then used to estimate the chi-square parameter m and genetic distances among
      marker loci. We discuss how to interpret the goodness-of-fit statistics
      appropriately when there are some recombination classes that have only a small
      number of observations. Finally, comparisons are made between the chi-square
      model and some other tractable models in the literature.

PMID- 7713409
TI  - Inferring weak selection from patterns of polymorphism and divergence at "silent"
      sites in Drosophila DNA.
AB  - Patterns of codon usage and "silent" DNA divergence suggest that natural
      selection discriminates among synonymous codons in Drosophila. "Preferred" codons
      are consistently found in higher frequencies within their synonymous families in
      Drosophila melanogaster genes. This suggests a simple model of silent DNA
      evolution where natural selection favors mutations from unpreferred to preferred
      codons (preferred changes). Changes in the opposite direction, from preferred to
      unpreferred synonymous codons (unpreferred changes), are selected against. Here,
      selection on synonymous DNA mutations is investigated by comparing the
      evolutionary dynamics of these two categories of silent DNA changes. Sequences
      from outgroups are used to determine the direction of synonymous DNA changes
      within and between D. melanogaster and Drosophila simulans for five genes.
      Population genetics theory shows that differences in the fitness effect of
      mutations can be inferred from the comparison of ratios of polymorphism to
      divergence. Unpreferred changes show a significantly higher ratio of polymorphism
      to divergence than preferred changes in the D. simulans lineage, confirming the
      action of selection at silent sites. An excess of unpreferred fixations in 28
      genes suggests a relaxation of selection on synonymous mutations in D.
      melanogaster. Estimates of selection coefficients for synonymous mutations (3.6 <
      magnitude of Nes < 1.3) in D. simulans are consistent with the reduced efficacy
      of natural selection (magnitude of Nes < 1) in the three- to sixfold smaller
      effective population size of D. melanogaster. Synonymous DNA changes appear to be
      a prevalent class of weakly selected mutations in Drosophila.

PMID- 7713410
TI  - Temporal allele frequency change and estimation of effective size in populations
      with overlapping generations.
AB  - In this paper we study the process of allele frequency change in finite
      populations with overlapping generations with the purpose of evaluating the
      possibility of estimating the effective size from observations of temporal
      frequency shifts of selectively neutral alleles. Focusing on allele frequency
      changes between successive cohorts (individuals born in particular years), we
      show that such changes are not determined by the effective population size alone,
      as they are when generations are discrete. Rather, in populations with
      overlapping generations, the amount of temporal allele frequency change is
      dependent on the age-specific survival and birth rates. Taking this phenomenon
      into account, we present an estimator for effective size that can be applied to
      populations with overlapping generations.

PMID- 7713412
TI  - The fifties and the renaissance in human and mammalian cytogenetics.

PMID- 7713411
TI  - Multilocus analysis for gene-centromere mapping using first polar bodies and
      secondary oocytes.
AB  - Polar body and oocyte typing is a new technique for gene-centromere mapping and
      for generating female linkage maps. A maximum likelihood approach is presented
      for ordering multiple markers relative to the centromere and for estimating
      recombination frequencies between markers and between the centromere and marker
      loci. Three marker-centromere orders are possible for each pair of markers: two
      orders when the centromere flanks the two markers and one order when the
      centromere is flanked by the two markers. For each possible order, the likelihood
      was expressed as a function of recombination frequencies for two adjacent
      intervals. LOD score for recombination frequency between markers or between the
      centromere and a marker locus was derived based on the likelihood for each gene
      centromere order. The methods developed herein provide a general solution to the
      problem of multilocus gene-centromere mapping that involves all theoretical
      crossover possibilities, including four-strand double crossovers.

PMID- 7713414
TI  - Mutations in GCR1, a transcriptional activator of Saccharomyces cerevisiae
      glycolytic genes, function as suppressors of gcr2 mutations.
AB  - The Saccharomyces cerevisiae GCR1 and GCR2 genes affect expression of most of the
      glycolytic genes. Evidence for Gcr1p/Gcr2p interaction has been presented earlier
      and is now supported by the isolation of mutations in Gcr1p suppressing gcr2, as
      assessed by growth and enzyme assay. Four specific mutation sites were
      identified. Together with use of the two-hybrid system of Fields and Song, they
      show that Gcr1p in its N-terminal half has a potential transcriptional activating
      function as well as elements for interaction with Gcr2p, which perhaps acts
      normally to expose an otherwise cryptic activation domain on Gcr1p.
      Complementation of various gcr1 mutant alleles and results with the two-hybrid
      system also indicate that Gcr1p itself normally functions as an oligomer.

PMID- 7713413
TI  - The sep1 mutant of Saccharomyces cerevisiae arrests in pachytene and is deficient
      in meiotic recombination.
AB  - Strand exchange protein 1 (Sep1) from Saccharomyces cerevisiae promotes
      homologous pairing of DNA in vitro and sep1 mutants display pleiotropic
      phenotypes in both vegetative and meiotic cells. In this study, we examined in
      detail the ability of the sep1 mutant to progress through meiosis I prophase and
      to undergo meiotic recombination. In meiotic return-to-growth experiments,
      commitment to meiotic recombination began at the same time in wild type and
      mutant; however, recombinants accumulated at decreased rates in the mutant. Gene
      conversion eventually reached nearly wild-type levels, whereas crossing over
      reached 15-50% of wild type. In an assay of intrachromosomal pop-out
      recombination, the sep1, dmc1 and rad51 single mutations had only small effects;
      however, pop-out recombination was virtually eliminated in the sep1 dmc1 and sep1
      rad51 double mutants, providing evidence for multiple recombination pathways.
      Analysis of meiotic recombination intermediates indicates that the sep1 mutant is
      deficient in meiotic double-strand break repair. In a physical assay, the
      formation of mature reciprocal recombinants in the sep1 mutant was delayed
      relative to wild type and ultimately reached only 50% of the wild-type level.
      Electron microscopic analysis of meiotic nuclear spreads indicates that the sep1
      delta mutant arrests in pachytene, with apparently normal synaptonemal complex.
      This arrest is RAD9-independent. We hypothesize that the Sep1 protein
      participates directly in meiotic recombination and that other strand exchange
      enzymes, acting in parallel recombination pathways, are able to substitute
      partially for the absence of the Sep1 protein.

PMID- 7713416
TI  - Identification of developmental regulatory genes in Aspergillus nidulans by
      overexpression.
AB  - Overexpression of several Aspergillus nidulans developmental regulatory genes has
      been shown to cause growth inhibition and development at inappropriate times. We
      set out to identify previously unknown developmental regulators by constructing a
      nutritionally inducible A. nidulans expression library containing small, random
      genomic DNA fragments inserted next to the alcA promoter [alcA(p)] in an A.
      nidulans transformation vector. Among 20,000 transformants containing random
      alcA(p) genomic DNA fusion constructs, we identified 66 distinct mutant strains
      in which alcA(p) induction resulted in growth inhibition as well as causing other
      detectable phenotypic changes. These growth inhibited mutants were divided into
      52 FIG (Forced expression Inhibition of Growth) and 14 FAB (Forced expression
      Activation of brlA) mutants based on whether or not alcA(p) induction resulted in
      accumulation of mRNA for the developmental regulatory gene brlA. In four FAB
      mutants, alcA(p) induction not only activated brlA expression but also caused
      hyphae to differentiate into reduced conidiophores that produced viable spores
      from the tips as is observed after alcA(p)::brlA induction. Sequence analyses of
      the DNA fragments under alcA(p) control in three of these four sporulating
      strains showed that in two cases developmental activation resulted from
      overexpression of previously uncharacterized genes, whereas in the third strain,
      the alcA(p) was fused to brlA. The potential uses for this strategy in
      identifying genes whose overexpression results in specific phenotypic changes
      like developmental induction are discussed.

PMID- 7713415
TI  - The Saccharomyces cerevisiae SPT7 gene encodes a very acidic protein important
      for transcription in vivo.
AB  - Mutations in the SPT7 gene of Saccharomyces cerevisiae originally were identified
      as suppressors of Ty and delta insertion mutations in the 5' regions of the HIS4
      and LYS2 genes. Other genes that have been identified in mutant hunts of this
      type have been shown to play a role in transcription. In this work we show that
      SPT7 is also important for proper transcription in vivo. We have cloned and
      sequenced the SPT7 gene and have shown that it encodes a large, acidic protein
      that is localized to the nucleus. The SPT7 protein contains a bromodomain
      sequence; a deletion that removes the bromodomain from the SPT7 protein causes no
      detectable mutant phenotype. Strains that contain an spt7 null mutation are
      viable but grow very slowly and have transcriptional defects at many loci
      including insertion mutations, Ty elements, the INO1 gene and the MFA1 gene.
      These transcriptional defects and other mutant phenotypes are similar to those
      caused by certain mutations in SPT15, which encodes the TATA binding protein
      (TBP). The similarity of the phenotypes of spt7 and spt15 mutants, including
      effects of spt7 mutations on the transcription start site of certain genes,
      suggests that SPT7 plays an important role in transcription initiation in vivo.

PMID- 7713417
TI  - Control of cleavage spindle orientation in Caenorhabditis elegans: the role of
      the genes par-2 and par-3.
AB  - Polarized asymmetric divisions play important roles in the development of plants
      and animals. The first two embryonic cleavages of Caenorhabditis elegans provide
      an opportunity to study the mechanisms controlling polarized asymmetric
      divisions. The first cleavage is unequal, producing daughters with different
      sizes and fates. The daughter blastomeres divide with different orientations at
      the second cleavage; the anterior blastomere divides equally across the long axis
      of the egg, whereas the posterior blastomere divides unequally along the long
      axis. We report here the results of our analysis of the genes par-2 and par-3
      with respect to their contribution to the polarity of these divisions. Strong
      loss-of-function mutations in both genes lead to an equal first cleavage and an
      altered second cleavage. Interestingly, the mutations exhibit striking gene
      specific differences at the second cleavage. The par-2 mutations lead to
      transverse spindle orientations in both blastomeres, whereas par-3 mutations lead
      to longitudinal spindle orientations in both blastomeres. The spindle orientation
      defects correlate with defects in centrosome movements during both the first and
      the second cell cycle. Temperature shift experiments with par-2(it5ts) indicate
      that the par-2(+) activity is not required after the two-cell stage. Analysis of
      double mutants shows that par-3 is epistatic to par-2. We propose a model wherein
      par-2(+) and par-3(+) act in concert during the first cell cycle to affect
      asymmetric modification of the cytoskeleton. This polar modification leads to
      different behaviors of centrosomes in the anterior and posterior and leads
      ultimately to blastomere-specific spindle orientations at the second cleavage.

PMID- 7713418
TI  - The fog-3 gene and regulation of cell fate in the germ line of Caenorhabditis
      elegans.
AB  - In the nematode Caenorhabditis elegans, germ cells normally adopt one of three
      fates: mitosis, spermatogenesis or oogenesis. We have identified and
      characterized the gene fog-3, which is required for germ cells to differentiate
      as sperm rather than as oocytes. Analysis of double mutants suggests that fog-3
      is absolutely required for spermatogenesis and acts at the end of the regulatory
      hierarchy controlling sex determination for the germ line. By contrast, mutations
      in fog-3 do not alter the sexual identity of other tissues. We also have
      characterized the null phenotype of fog-1, another gene required for
      spermatogenesis; we demonstrate that it too controls the sexual identity of germ
      cells but not of other tissues. Finally, we have studied the interaction of these
      two fog genes with gld-1, a gene required for germ cells to undergo oogenesis
      rather than mitosis. On the basis of these results, we propose that germ-cell
      fate might be controlled by a set of inhibitory interactions among genes that
      specify one of three fates: mitosis, spermatogenesis or oogenesis. Such a
      regulatory network would link the adoption of one germ-cell fate to the
      suppression of the other two.

PMID- 7713419
TI  - gld-1, a tumor suppressor gene required for oocyte development in Caenorhabditis
      elegans.
AB  - We have characterized 31 mutations in the gld-1 (defective in germline
      development) gene of Caenorhabditis elegans. In gld-1 (null) hermaphrodites,
      oogenesis is abolished and a germline tumor forms where oocyte development would
      normally occur. By contrast, gld-1 (null) males are unaffected. The hermaphrodite
      germline tumor appears to derive from germ cells that enter the meiotic pathway
      normally but then exit pachytene and return to the mitotic cycle. Certain gld-1
      partial loss-of-function mutations also abolish oogenesis, but germ cells arrest
      in pachytene rather than returning to mitosis. Our results indicate that gld-1 is
      a tumor suppressor gene required for oocyte development. The tumorous phenotype
      suggests that gld-1(+) may function to negatively regulate proliferation during
      meiotic prophase and/or act to direct progression through meiotic prophase. We
      also show that gld-1(+) has an additional nonessential role in germline sex
      determination: promotion of hermaphrodite spermatogenesis. This function of gld-1
      is inferred from a haplo-insufficient phenotype and from the properties of gain
      of-function gld-1 mutations that cause alterations in the sexual identity of germ
      cells.

PMID- 7713420
TI  - Analysis of the multiple roles of gld-1 in germline development: interactions
      with the sex determination cascade and the glp-1 signaling pathway.
AB  - The Caenorhabditis elegans gene gld-1 is essential for oocyte development; in gld
      1 (null) hermaphrodites, a tumor forms where oogenesis would normally occur. We
      use genetic epistasis analysis to demonstrate that tumor formation is dependent
      on the sexual fate of the germline. When the germline sex determination pathway
      is set in the female mode (terminal fem/fog genes inactive), gld-1 (null) germ
      cells exit meiotic prophase and proliferate to form a tumor, but when the pathway
      is set in the male mode, they develop into sperm. We conclude that the gld-1
      (null) phenotype is cell-type specific and that gld-1(+) acts at the end of the
      cascade to direct oogenesis. We also use cell ablation and epistasis analysis to
      examine the dependence of tumor formation on the glp-1 signaling pathway.
      Although glp-1 activity promotes tumor growth, it is not essential for tumor
      formation by gld-1 (null) germ cells. These data also reveal that gld-1(+) plays
      a nonessential (and sex nonspecific) role in regulating germ cell proliferation
      before their entry into meiosis. Thus gld-1(+) may negatively regulate
      proliferation at two distinct points in germ cell development: before entry into
      meiotic prophase in both sexes (nonessential premeiotic gld-1 function) and
      during meiotic prophase when the sex determination pathway is set in the female
      mode (essential meiotic gld-1 function).

PMID- 7713421
TI  - Transposon insertions causing constitutive Sex-lethal activity in Drosophila
      melanogaster affect Sxl sex-specific transcript splicing.
AB  - Sex-lethal (Sxl) gene products induce female development in Drosophila
      melanogaster and suppress the transcriptional hyperactivation of X-linked genes
      responsible for male X-chromosome dosage compensation. Control of Sxl functioning
      by the dose of X-chromosomes normally ensures that the female-specific functions
      of this developmental switch gene are only expressed in diplo-X individuals.
      Although the immediate effect of X-chromosome dose is on Sxl transcription,
      during most of the life cycle "on" vs. "off" reflects alternative Sxl RNA
      splicing, with the female (productive) splicing mode maintained by a positive
      feedback activity of SXL protein on Sxl pre-mRNA splicing. "Male-lethal" (SxlM)
      gain-of-function alleles subvert Sxl control by X-chromosome dose, allowing
      female Sxl functions to be expressed independent of the positive regulators
      upstream of Sxl. As a consequence, SxlM haplo-X animals (chromosomal males) die
      because of improper dosage compensation, and SxlM chromosomal females survive the
      otherwise lethal effects of mutations in upstream positive regulators. Five
      independent spontaneous SxlM alleles were shown previously to be transposon
      insertions into what was subsequently found to be the region of regulated sex
      specific Sxl RNA splicing. We show that these five alleles represent three
      different mutant types: SxlM1, SxlM3, and SxlM4. SxlM1 is an insertion of a roo
      element 674 bp downstream of the translation-terminating male-specific exon.
      SxlM3 is an insertion of a hobo transposon (not 297 as previously reported) into
      the 3' splice site of the male exon, and SxlM4 is an insertion of a novel
      transposon into the male-specific exon itself. We show that these three gain-of
      function mutants differ considerably in their ability to bypass the sex
      determination signal, with SxlM4 being the strongest and SxlM1 the weakest. This
      difference is also reflected in effects of these mutations on sex-specific RNA
      splicing and on the rate of appearance of SXL protein in male embryos. Transcript
      analysis of double-mutant male-viable SxlM derivatives in which the SxlM
      insertion is cis to loss-of-function mutations, combined with other results
      reported here, indicates that the constitutive character of these SxlM alleles is
      a consequence of an alteration of the structure of the pre-mRNA that allows some
      level of female splicing to occur even in the absence of functional SXL protein.
      Surprisingly, however, most of the constitutive character of SxlM alleles appears
      to depend on the mutant alleles' responsiveness, perhaps greater than wild-type,
      to the autoregulatory splicing activity of the wild-type SXL proteins they
      produce.

PMID- 7713422
TI  - The cross-linking agent hexamethylphosphoramide predominantly induces intra-locus
      and multi-locus deletions in postmeiotic germ cells of Drosophila.
AB  - The nature of DNA sequence changes induced by the cross-linking agent
      hexamethylphosphoramide (HMPA) within and in the vicinity of the vermilion locus
      of Drosophila melanogaster that produce a vermilion mutant phenotype was analyzed
      after exposure of postmeiotic male germ cells. Mutagenized males were mated to
      either females wild-type (exr+) for nucleotide excision repair (NER) or to
      females having a deficiency (exr-) for NER. Rearrangements, mostly deletions,
      represented by far the most frequent type of mutational events induced by HMPA
      that are detected as vermilion mutations. In the exr+ group, all but one (a
      double substitution) of 21 mutants characterized were large sequence changes: we
      found 5 intra-locus deletions, 3 intra-locus deletions associated with insertions
      and 12 multi-locus deletions. When taken together, deletions and
      deletion/insertion mutations represent 96% of the HMPA-induced DNA modifications
      obtained under proficient repair conditions. Of the 10 mutants obtained from
      crosses with exr- females, 6 intra-locus and 2 multi-locus deletions were found,
      as opposed to just 1 point mutation and 1 double substitution. The
      "hypomutability effect" observed with exr- genotypes in relation to the wild type
      seems to be caused by a decrease in the frequency of multi-locus deletions in the
      former group. The results suggest that the NER system is involved in the
      generation of multi-locus deletions, whereas intra-locus deletions appear to be
      formed through a postreplication slipped-misrepair pathway. It is concluded that
      an eukaryotic in vivo system with no limitations for the recovery of multi-locus
      deletions, such as vermilion, should be used for the analysis of DNA damage
      induced by cross-linking agents.

PMID- 7713423
TI  - The Drosophila salivary gland chromocenter contains highly polytenized subdomains
      of mitotic heterochromatin.
AB  - Peri-centromeric regions of Drosophila melanogaster chromosomes appear
      heterochromatic in mitotic cells and become greatly underrepresented in giant
      polytene chromosomes, where they aggregate into a central mass called the
      chromocenter. We used P elements inserted at sites dispersed throughout much of
      the mitotic heterochromatin to analyze the fate of 31 individual sites during
      polytenization. Analysis of DNA sequences flanking many of these elements
      revealed that middle repetitive or unique sequence DNAs frequently are
      interspersed with satellite DNAs in mitotic heterochromatin. All nine Y
      chromosome sites tested were underrepresented > 20-fold on Southern blots of
      polytene DNA and were rarely or never detected by in situ hybridization to
      salivary gland chromosomes. In contrast, nine tested insertions in autosomal
      centromeric heterochromatin were represented fully in salivary gland DNA, despite
      the fact that at least six were located proximal to known blocks of satellite
      DNA. The inserted sequences formed diverse, site-specific morphologies in the
      chromocenter of salivary gland chromosomes, suggesting that domains dispersed at
      multiple sites in the centromeric heterochromatin of mitotic chromosomes
      contribute to polytene beta-heterochromatin. We suggest that regions containing
      heterochromatic genes are organized into dispersed chromatin configurations that
      are important for their function in vivo.

PMID- 7713424
TI  - Vertical transmission of the retrotransposable elements R1 and R2 during the
      evolution of the Drosophila melanogaster species subgroup.
AB  - R1 and R2 are non-long-terminal repeat retrotransposable elements that insert
      into specific sequences of insect 28S ribosomal RNA genes. These elements have
      been extensively described in Drosophila melanogaster. To determine whether these
      elements have been horizontally or vertically transmitted, we characterized R1
      and R2 elements from the seven other members of the melanogaster species subgroup
      by genomic blotting and nucleotide sequencing. Each species was found to have
      homogeneous families of R1 and R2 elements with the exception of erecta and
      orena, which have no R2 elements. The DNA sequences of multiple R1 and R2 copies
      from each species indicated nucleotide divergence within each species averaged
      only 0.48% for R1 and 0.35% for R2, well below the level of divergence among the
      species. Most copies of R1 and R2 (40 of 47) sequenced from the seven species
      were potentially functional, as indicated by the absence of premature termination
      codons or translational frameshifts that would destroy the open reading frame of
      the element. The sequence relationships of both the R1 and R2 elements from the
      various members of the melanogaster subgroup closely followed that of the species
      phylogeny, suggesting that R1 and R2 have been stably maintained by vertical
      transmission since the origin of this species subgroup 17-20 million years ago.
      The remarkable stability of R1 and R2, compared to what has been suggested for
      transposable elements that insert at multiple locations in these same species,
      may be due to their unique specificity for sites in the rRNA gene locus. Under
      low copy number conditions, when it is essential for any mobile element to
      transpose, the insertion specificities of R1 and R2 ensure uniform
      developmentally regulated target sites that can be occupied with little or no
      detrimental effect on the host.

PMID- 7713426
TI  - Flamenco, a gene controlling the gypsy retrovirus of Drosophila melanogaster.
AB  - Gypsy is an endogenous retrovirus of Drosophila melanogaster. It is stable and
      does not transpose with detectable frequencies in most Drosophila strains.
      However, we have characterized unstable strains, known as MG, in which it
      transposes at high frequency. These stocks contain more copies of gypsy than
      usual stocks. Transposition results in mutations in several genes such as ovo and
      cut. They are stable and are due to gypsy insertions. Integrations into the ovoD1
      female sterile-dominant mutation result in a null allele of the gene and
      occurrence of fertile females. This phenomenon, known as the ovoD1 reversion
      assay, can be used to quantitate gypsy activity. We have shown that the
      properties of MG strains result from mutation of a host gene that we called
      flamenco (flam). It has a strict maternal effect on gypsy mobilization:
      transposition occurs at high frequency only in the germ line of the progeny of
      females homozygous for mutations of the gene. It is located at position 65.9
      (20A1-3) on the X chromosome. The mutant allele present in MG strains is
      essentially recessive. Flamenco seems to control the infective properties of
      gypsy.

PMID- 7713425
TI  - R1 and R2 retrotransposable elements of Drosophila evolve at rates similar to
      those of nuclear genes.
AB  - The non-long-terminal repeat retrotransposable elements, R1 and R2, insert at
      unique locations in the 28S ribosomal RNA genes of insects. Based on the
      nucleotide sequences of these elements in the eight members of the melanogaster
      species subgroup of the genus Drosophila, they have been maintained by vertical
      germline transmission for the 17-20 million year history of this subgroup. The
      stable inheritance of R1 and R2 within these species has enabled a determination
      of their nucleotide substitution rates. The sequence of the R1 and R2 elements
      from D. ambigua, a member of the obscura species group, has also been determined
      to enable an extrapolation of this rate over an estimated 45-60 million years.
      The mean rate of substitutions at synonymous sites (Ks) was 6.6 and 9.6 times the
      rate at replacement sites (Ka) in the R1 and R2 elements, respectively. Both
      elements appear to have been under selective pressure to maintain their open
      reading frames and thus their ability to retrotranspose for most of their
      evolution in these lineages. Using the rate of change at synonymous sites (Ks) as
      the best indicator of the nucleotide substitution rate, the mean Ks values for R1
      and R2 were 2.3 and 2.2 times that of the alcohol dehydrogenase (Adh) genes.
      However, this faster rate is a result of the lower codon usage bias of R1 and R2
      compared with that of Adh. When the Ks rates of R1 and R2 were compared with that
      of a larger number of nuclear genes available from at least two of the nine
      species under investigation, R1 and R2 were found to evolve in most lineages at
      rates similar to that of nuclear genes with low codon bias. The ability of R1 and
      R2 to maintain their presence in this species subgroup by retrotransposition
      while exhibiting rates of nucleotide evolution similar to nuclear genes suggests
      these transposition events are rare or not as error prone as that of
      retroviruses.

PMID- 7713427
TI  - Identification of regions interacting with ovoD mutations: potential new genes
      involved in germline sex determination or differentiation in Drosophila
      melanogaster.
AB  - Only a few Drosophila melanogaster germline sex determination genes are known,
      and there have been no systematic screens to identify new genes involved in this
      important biological process. The ovarian phenotypes produced by females mutant
      for dominant alleles of the ovo gene are modified in flies with altered doses of
      other loci involved in germline sex determination in Drosophila (Sex-lethal+,
      sans fille+ and ovarian tumor+). This observation constitutes the basis for a
      screen to identify additional genes required for proper establishment of germline
      sexual identity. We tested 300 deletions, which together cover approximately 58%
      of the euchromatic portion of the genome, for genetic interactions with ovoD.
      Hemizygosity for more than a dozen small regions show interactions that either
      partially suppress or enhance the ovarian phenotypes of females mutant for one or
      more of the three dominant ovo mutations. These regions probably contain genes
      whose products act in developmental hierarchies that include ovo+ protein.

PMID- 7713428
TI  - Dosage compensation of the Drosophila white gene requires both the X chromosome
      environment and multiple intragenic elements.
AB  - The X-linked white gene when transposed to autosomes retains only partial dosage
      compensation. One copy of the gene in males expresses more than one copy but less
      than two copies in females. When inserted in ectopic X chromosome sites, the mini
      white gene of the CaspeR vector can be fully dosage compensated and can even
      achieve hyperdosage compensation, meaning that one copy in males gives more
      expression than two copies in females. As sequences are removed gradually from
      the 5' end of the gene, we observe a progressive transition from hyperdosage
      compensation to full dosage compensation to partial dosage compensation. When the
      deletion reaches -17, the gene can no longer dosage compensate fully even on the
      X chromosome. A deletion reaching +173, 4 bp preceding the AUG initiation codon,
      further reduces dosage compensation both on the X chromosome and on autosomes.
      This truncated gene can still partially dosage compensate on autosomes,
      indicating the presence of dosage compensation determinants in the protein coding
      region. We conclude that full dosage compensation requires an X chromosome
      environment and that the white gene contains multiple dosage-compensation
      determinants, some near the promoter and some in the coding region.

PMID- 7713430
TI  - An inverse PCR screen for the detection of P element insertions in cloned genomic
      intervals in Drosophila melanogaster.
AB  - We developed a screening approach that utilizes an inverse polymerase chain
      reaction (PCR) to detect P element insertions in or near previously cloned genes
      in Drosophila melanogaster. We used this approach in a large scale genetic screen
      in which P elements were mobilized from sites on the X chromosome to new
      autosomal locations. Mutagenized flies were combined in pools, and our screening
      approach was used to generate probes corresponding to the sequences flanking each
      site of insertion. These probes then were used for hybridization to cloned
      genomic intervals, allowing individuals carrying insertions in them to be
      detected. We used the same approach to perform repeated rounds of sib-selection
      to generate stable insertion lines. We screened 16,100 insert bearing individuals
      and recovered 11 insertions in five intervals containing genes encoding members
      of the kinesin superfamily in Drosophila melanogaster. In addition, we recovered
      an insertion in the region including the Larval Serum Protein-2 gene. Examination
      by Southern hybridization confirms that the lines we recovered represent genuine
      insertions in the corresponding genomic intervals. Our data indicates that this
      approach will be very efficient both for P element mutagenesis of new genomic
      regions and for detection and recovery of "local" P element transposition events.
      In addition, our data constitutes a survey of preferred P element insertion sites
      in the Drosophila genome and suggests that insertion sites that are mutable at a
      rate of approximately 10(-4) are distributed every 40-50 kb.

PMID- 7713429
TI  - Drawing a stripe in Drosophila imaginal disks: negative regulation of
      decapentaplegic and patched expression by engrailed.
AB  - During development of the Drosophila adult appendage precursors, the larval
      imaginal disks, the decapentaplegic (dpp) gene is expressed in a stripe just
      anterior to the anterior/posterior (A/P) compartment boundary. Here, we
      investigate the genetic controls that lead to production of this stripe. We
      extend previous observations on leaky engrailed (en) mutations by showing that
      mutant clones completely lacking both en and invected (inv) activity ectopically
      express dpp-lacZ reporter genes in the posterior compartment, where dpp activity
      ordinarily is repressed. Similarly, patched (ptc) is also ectopically expressed
      in such posterior compartment en-inv- null clones. In contrast, these en-inv-
      clones exhibit loss of hedgehog (hh) expression. We suggest that the absence of
      dpp expression in the posterior compartment is due to direct repression by en.
      Ubiquitious expression of en in imaginal disks, produced by a hs-en construct,
      eliminates the expression of dpp-lacZ in its normal A/P boundary stripe. We
      identify three in vitro Engrailed binding sites in one of our dpp-lacZ reporter
      gene. Mutagenesis of these Engrailed binding sites results in ectopic expression
      of this reporter gene, but does not alter the normal stripe of expression at the
      A/P boundary. We propose that the en-hh-ptc regulatory loop that is responsible
      for segmental expression of wingless in the embryo is reutilized in imaginal
      disks to create a stripe of dpp expression along the A/P compartment boundary.

PMID- 7713431
TI  - Spontaneous mutation rate of modifiers of metabolism in Drosophila.
AB  - A rigorous test of our understanding of evolutionary quantitative genetics would
      be to predict accurately the equilibrium distribution of a character from
      empirical estimates of the relevant parameters in a mutation-selection-drift
      balance model. An aspect of this problem that is amenable to experimental
      analysis is the distribution of the effects of new mutations. This study
      quantifies the divergence among 200 lines of Drosophila melanogaster as they
      accumulated mutations on the second chromosome and estimates the rate of increase
      of variation and covariation in metabolic characters. Amounts of stored
      triacylglycerol and glycogen and the activities of a series of 12 metabolic
      enzymes were assayed in a subset of lines at generations 0, 11, 22, 33 and 44.
      Analyses of the rate of increase in the among-line variance in each trait allowed
      estimation of Vm/Ve, the ratio of among-line variance added per generation to the
      environmental variance. Values of Vm/Ve for the second chromosome ranged from
      0.0004 to 0.0289 per generation. Six of the 16 characters showed significant
      departure from a normal distribution, and several lines exhibited large changes
      in more than one character. The covariance of pairs of traits also was
      partitioned into a within-line component (environmental covariance, Cov(e)) and
      an among-line component (mutational covariance, Covm). Both variances and
      covariance among lines increased over time, as assessed by linear regression,
      whereas environmental covariance showed no such trend. Results indicate that the
      quantitative genetic parameters describing the variation in metabolic traits are
      similar to those of other continuous characters.

PMID- 7713432
TI  - Characterization of the cis-regulatory region of the Drosophila homeotic gene Sex
      combs reduced.
AB  - The Drosophila homeotic gene Sex combs reduced (Scr) controls the segmental
      identity of the labial and prothoracic segments in the embryo and adult. It
      encodes a sequence-specific transcription factor that controls, in concert with
      other gene products, differentiative pathways of tissues in which Scr is
      expressed. During embryogenesis, Scr accumulation is observed in a discrete
      spatiotemporal pattern that includes the labial and prothoracic ectoderm, the
      subesophageal ganglion of the ventral nerve cord and the visceral mesoderm of the
      anterior and posterior midgut. Previous analyses have demonstrated that
      breakpoint mutations located in a 75-kb interval, including the Scr transcription
      unit and 50 kb of upstream DNA, cause Scr misexpression during development,
      presumably because these mutations remove Scr cis-regulatory sequences from the
      proximity of the Scr promoter. To gain a better understanding of the regulatory
      interactions necessary for the control of Scr transcription during embryogenesis,
      we have begun a molecular analysis of the Scr regulatory interval. DNA fragments
      from this 75-kb region were subcloned into P-element vectors containing either an
      Scr-lacZ or hsp70-lacZ fusion gene, and patterns of reporter gene expression were
      assayed in transgenic embryos. Several fragments appear to contain Scr regulatory
      sequences, as they direct reporter gene expression in patterns similar to those
      normally observed for Scr, whereas other DNA fragments direct Scr reporter gene
      expression in developmentally interesting but non-Scr-like patterns during
      embryogenesis. Scr expression in some tissues appears to be controlled by
      multiple regulatory elements that are separated, in some cases, by more than 20
      kb of intervening DNA. Interestingly, regulatory sequences that direct reporter
      gene expression in an Scr-like pattern in the anterior and posterior midgut are
      imbedded in the regulatory region of the segmentation gene fushi tarazu (ftz),
      which is normally located between 10 and 20 kb 5' of the Scr transcription start
      site. This analysis provides an entry point for the study of how Scr
      transcription is regulated at the molecular level.

PMID- 7713433
TI  - Identification of Polycomb and trithorax group responsive elements in the
      regulatory region of the Drosophila homeotic gene Sex combs reduced.
AB  - The Drosophila homeotic gene Sex combs reduced (Scr) is necessary for the
      establishment and maintenance of the morphological identity of the labial and
      prothoracic segments. In the early embryo, its expression pattern is established
      through the activity of several gap and segmentation gene products, as well as
      other transcription factors. Once established, the Polycomb group (Pc-G) and
      trithorax group (trx-G) gene products maintain the spatial pattern of Scr
      expression for the remainder of development. We report the identification of DNA
      fragments in the Scr regulatory region that may be important for its regulation
      by Polycomb and trithorax group gene products. When DNA fragments containing
      these regulatory sequences are subcloned into P-element vectors containing a
      white minigene, transformants containing these constructs exhibit mosaic patterns
      of pigmentation in the adult eye, indicating that white minigene expression is
      repressed in a clonally heritable manner. The size of pigmented and nonpigmented
      clones in the adult eye suggests that the event determining whether a cell in the
      eye anlagen will express white occurs at least as early as the first larval
      instar. The amount of white minigene repression is reduced in some Polycomb group
      mutants, whereas repression is enhanced in flies mutant for a subset of trithorax
      group loci. The repressor activity of one fragment, normally located in Scr
      Intron 2, is increased when it is able to homologously pair, a property
      consistent with genetic data suggesting that Scr exhibits transvection. Another
      Scr regulatory fragment, normally located 40 kb upstream of the Scr promoter,
      silences ectopic expression of an Scr-lacZ fusion gene in the embryo and does so
      in a Polycomb-dependent manner. We propose that the regulatory sequences located
      within these DNA fragments may normally mediate the regulation of Scr by proteins
      encoded by members of the Polycomb and trithorax group loci.

PMID- 7713434
TI  - Transvection in the iab-5,6,7 region of the bithorax complex of Drosophila:
      homology independent interactions in trans.
AB  - The Abdominal-B (Abd-B) gene of the bithorax complex (BX-C) of Drosophila
      controls the identities of the fifth through seventh abdominal segments and
      segments in the genitalia (more precisely, parasegments 10-14). Here we focus on
      iab-5, iab-6 and iab-7, regulatory regions of Abd-B that control expression in
      the fifth, sixth and seventh abdominal segments (parasegments 10-12). By analysis
      of partial BX-C deficiencies, we show that these regions are able to promote
      fifth and sixth abdominal segment identities in the absence of an Abd-B gene in
      cis. We establish that this ability does not result from cis-regulation of the
      adjacent abd-A or Ubx genes of the BX-C but rather occurs because the iab-5,6,7
      region is able to interact with Abd-B in trans. We demonstrate that this
      interaction is proximity dependent and is, therefore, a case of what E. B. Lewis
      has called transvection. Interactions of this type are presumably facilitated by
      the synapsis of homologues that occurs in somatic cells of Dipterans. Although
      transvection has been detected in a number of Drosophila genes, transvection of
      the iab-5,6,7 region is exceptional in two ways. First, interaction in trans with
      Abd-B does not require that homologues share homologous sequences within, or for
      some distance to either side of, the BX-C. This is the first case of transvection
      shown to be independent of local synapsis. A second unusual feature of iab-5,6,7
      transvection is that it is remarkably difficult to disrupt by heterozygosity for
      chromosome rearrangements. The lack of requirement for local synapsis and the
      tenacity of trans-interaction argue that the iab-5,6,7 region can locate and
      interact with Abd-B over considerable distance. This is consistent with the
      normal role of iab-5,6,7, which must act over some 20-60 kb to influence its
      regulatory target in cis at the Abd-B promoter. Evidence is presented that trans
      action of iab-5,6,7 requires, and may be mediated by, the region between distal
      iab-7 and Abd-B. Also, we show that iab-5,6,7 transvection is independent of the
      allelic state of zeste, a gene that influences several other cases of
      transvection. The long-range nature of interactions in trans between iab-5,6,7
      and Abd-B suggests that similar interactions could operate effectively in
      organisms lacking extensive somatic pairing. Transvection may, therefore, be of
      more general significance than previously suspected.

PMID- 7713436
TI  - Polygenic mutation in Drosophila melanogaster: non-linear divergence among
      unselected strains.
AB  - A highly inbred strain of Drosophila melanogaster was subdivided into 20
      replicate sublines that were maintained independently with 10 pairs of randomly
      sampled parents per generation for 180 generations. The variance between lines in
      abdominal and sternopleural bristle number increased little after 100
      generations, in contrast to the neutral expectation of a linear increase; and the
      covariances of line means between different generations declined with increasing
      number of generations apart, in contrast to the neutral expectation of constant
      covariance. Thus, under a neutral model, the estimates of mutational variance
      were lower than for previous estimates from the first 100 generations of subline
      divergence. An autoregressive model was fitted to the variance of line means that
      indicated strong natural selection. There is no single unequivocal explanation
      for the results. Possible and nonexclusive alternatives include stabilizing
      selection on bristle number and deleterious effects on fitness of bristle
      mutations. The inferred strengths of selection on both traits are too high for
      stabilizing selection alone, and the between-line variance did not continue to
      increase sufficiently for pleiotropy alone to account for the observations. A
      third potential explanation that does not invoke selection is duplicate epistasis
      between mutations affecting bristle number.

PMID- 7713437
TI  - Polygenic mutation in Drosophila melanogaster: the causal relationship of bristle
      number to fitness.
AB  - The association between sternopleural and abdominal bristle number and fitness in
      Drosophila melanogaster was determined for sublines of an initially highly inbred
      strain that were maintained by divergent artificial selection for 150 generations
      or by random mating for 180 generations. Replicate selection lines had more
      extreme bristle numbers than those that were maintained without artificial
      selection at the same census size for approximately the same number of
      generations. The average fitness, estimated by a single generation of competition
      against a compound autosome strain, was 0.17 for lines selected for high and low
      abdominal bristle numbers and 0.19 for lines selected for high and low
      sternopleural bristle number. The average fitness of unselected lines, 0.46, was
      significantly higher than that of the selection lines. The fitnesses and the
      relationships of bristle number to fitness in progeny of all possible crosses of
      high x high (H x H), high x low (H x L) and low x low (L x L) selection lines
      were examined to determine whether the observed intermediate optima were caused
      by direct stabilizing selection on bristle number or by apparent stabilizing
      selection mediated through deleterious pleiotropic fitness effects of mutations
      affecting bristle number. Although bristle number was nearly additive for progeny
      of H x H, H x L and L x L crosses among sternopleural bristle selection lines,
      their mean fitnesses were not significantly different from each other, or from
      the mean fitness of the unselected lines, suggesting partly or completely
      recessive pleiotropic fitness effects cause apparent stabilizing selection. The
      average fitness of the progeny of H x H abdominal bristle selection lines was not
      significantly different from the fitness of unselected lines, but the mean
      fitness of the progeny of L x L crosses was not significantly different from that
      of the pure low lines. This is consistent with direct selection against low but
      not high abdominal bristle number, but the interpretation is confounded by
      variation in average degree of dominance for fitness (on average recessive in the
      high abdominal bristle selection lines and additive in the low abdominal bristle
      selection lines). Neither direct stabilizing selection nor pleiotropy, therefore,
      can account for all the observations.

PMID- 7713435
TI  - Cis and trans interactions between the iab regulatory regions and abdominal-A and
      abdominal-B in Drosophila melanogaster.
AB  - The infra-abdominal (iab) elements in the bithorax complex of Drosophila
      melanogaster regulate the transcription of the homeotic genes abdominal-A (abd-A)
      and Abdominal-B (Abd-B) in cis. Here we describe two unusual aspects of
      regulation by the iab elements, revealed by an analysis of an unexpected
      complementation between mutations in the Abd-B transcription unit and these
      regulatory regions. First, we find that iab-6 and iab-7 can regulate Abd-B in
      trans. This iab trans regulation is insensitive to chromosomal rearrangements
      that disrupt transvection effects at the nearby Ubx locus. In addition, we show
      that a transposed Abd-B transcription unit and promoter on the Y chromosome can
      be activated by iab elements located on the third chromosome. These results
      suggest that the iab regions can regulate their target promoter located at a
      distant site in the genome in a manner that is much less dependent on homologue
      pairing than other transvection effects. The iab regulatory regions may have a
      very strong affinity for the target promoter, allowing them to interact with each
      other despite the inhibitory effects of chromosomal rearrangements. Second, by
      generating abd-A mutations on rearrangement chromosomes that break in the iab-7
      region, we show that these breaks induce the iab elements to switch their target
      promoter from Abd-B to abd-A. These two unusual aspects of iab regulation are
      related by the iab-7 breakpoint chromosomes that prevent iab elements from acting
      on Abd-B and allow them to act on abd-A. We propose that the iab-7 breaks prevent
      both iab trans regulation and target specificity by disrupting a mechanism that
      targets the iab regions to the Abd-B promoter.

PMID- 7713438
TI  - Complete sequence of a sea lamprey (Petromyzon marinus) mitochondrial genome:
      early establishment of the vertebrate genome organization.
AB  - The complete nucleotide sequence of a sea lamprey (Petromyzon marinus)
      mitochondrial genome has been determined. The lamprey genome is 16,201 bp in
      length and contains genes for 13 proteins, two rRNAs, 22 tRNAs and two major
      noncoding regions. The order and transcriptional polarities of protein-coding
      genes are basically identical to those of other chordate mtDNAs, demonstrating
      that the common mitochondrial gene organization of vertebrates was established at
      an early stage of vertebrate evolution. The two major noncoding regions are
      separated by two tRNA genes. The first region probably functions as the control
      region because it contains distinctive conserved sequence blocks (CSB-II and III)
      common to other vertebrate control regions. The central conserved domain observed
      in other vertebrate control regions is not found in the lamprey, suggesting that
      it is a recently evolved functional domain in vertebrates. Noncoding segments are
      not found in the expected position of the origin of replication for the second
      strand, suggesting either that one of the tRNA genes has a dual function or that
      the second noncoding region may function as the second-strand origin. The base
      composition at the wobble positions of fourfold degenerate codon families is
      highly biased toward thymine (32.7%). Values of GC- and AT-skew are typical of
      vertebrate mitochondrial genomes.

PMID- 7713439
TI  - A large-scale gene-trap screen for insertional mutations in developmentally
      regulated genes in mice.
AB  - We have used a gene-trap vector and mouse embryonic stem (ES) cells to screen for
      insertional mutations in genes developmentally regulated at 8.5 days of
      embryogenesis (dpc). From 38,730 cell lines with vector insertions, 393 clonal
      integrations had disrupted active transcription units, as assayed by beta
      galactosidase reporter gene expression. From these lines, 290 clones were
      recovered and injected into blastocysts to assay for reporter gene expression in
      8.5-dpc chimeric mouse embryos. Of these, 279 clones provided a sufficient number
      of chimeric embryos for analysis. Thirty-six (13%) showed restricted patterns of
      reporter-gene expression, 88 (32%) showed widespread expression and 155 (55%)
      failed to show detectable levels of expression. Further analysis showed that
      approximately one-third of the clones that did not express detectable levels of
      the reporter gene at 8.5 dpc displayed reporter gene activity at 12.5 dpc. Thus,
      a large proportion of the genes that are expressed in ES cells are either
      temporally or spatially regulated during embryogenesis. These results indicate
      that gene-trap mutageneses in embryonic stem cells provide an effective approach
      for isolating mutations in a large number of developmentally regulated genes.

PMID- 7713440
TI  - Mus spretus LINE-1 sequences detected in the Mus musculus inbred strain C57BL/6J
      using LINE-1 DNA probes.
AB  - The inbred mouse strain, C57BL/6J, was derived from mice of the Mus musculus
      complex. C57BL/6J can be crossed in the laboratory with a closely related mouse
      species, M. spretus to produce fertile offspring; however there has been no
      previous evidence of gene flow between M. spretus and M. musculus in nature.
      Analysis of the repetitive sequence LINE-1, using both direct sequence analysis
      and genomic Southern blot hybridization to species-specific LINE-1 hybridization
      probes, demonstrates the presence of LINE-1 elements in C57BL/6J that were
      derived from the species M. spretus. These spretus-like LINE-1 elements in
      C57BL/6J reveal a cross to M. spretus somewhere in the history of C57BL/6J. It is
      unclear if the spretus-like LINE-1 elements are still embedded in flanking DNA
      derived from M. spretus or if they have transposed to new sites. The number of
      spretus-like elements detected suggests a maximum of 6.5% of the C57BL/6J genome
      may be derived from M. spretus.

PMID- 7713441
TI  - Mapping quantitative trait loci controlling milk production in dairy cattle by
      exploiting progeny testing.
AB  - We have exploited "progeny testing" to map quantitative trait loci (QTL)
      underlying the genetic variation of milk production in a selected dairy cattle
      population. A total of 1,518 sires, with progeny tests based on the milking
      performances of > 150,000 daughters jointly, was genotyped for 159 autosomal
      microsatellites bracketing 1645 centimorgan or approximately two thirds of the
      bovine genome. Using a maximum likelihood multilocus linkage analysis accounting
      for variance heterogeneity of the phenotypes, we identified five chromosomes
      giving very strong evidence (LOD score > or = 3) for the presence of a QTL
      controlling milk production: chromosomes 1, 6, 9, 10 and 20. These findings
      demonstrate that loci with considerable effects on milk production are still
      segregating in highly selected populations and pave the way toward marker
      assisted selection in dairy cattle breeding.

PMID- 7713442
TI  - Structure and evolution of genes encoding polyubiquitin and ubiquitin-like
      proteins in Arabidopsis thaliana ecotype Columbia.
AB  - The Arabidopsis thaliana ecotype Columbia ubiquitin gene family consists of 14
      members that can be divided into three types of ubiquitin genes; polyubiquitin
      genes, ubiquitin-like genes and ubiquitin extension genes. The isolation and
      characterization of eight ubiquitin sequences, consisting of four polyubiquitin
      genes and four ubiquitin-like genes, are described here, and their relationships
      to each other and to previously identified Arabidopsis ubiquitin genes were
      analyzed. The polyubiquitin genes, UBQ3, UBQ10, UBQ11 and UBQ14, contain tandem
      repeats of the 228-bp ubiquitin coding region. Together with a previously
      described polyubiquitin gene, UBQ4, they differ in synonymous substitutions,
      number of ubiquitin coding regions, number and nature of nonubiquitin C-terminal
      amino acid(s) and chromosomal location, dividing into two subtypes; the UBQ3/UBQ4
      and UBQ10/UBQ11/UBQ14 subtypes. Ubiquitin-like genes, UBQ7, UBQ8, UBQ9 and UBQ12,
      also contain tandem repeats of the ubiquitin coding region, but at least one
      repeat per gene encodes a protein with amino acid substitutions. Nucleotide
      comparisons, Ks value determinations and neighbor-joining analyses were employed
      to determine intra- and intergenic relationships. In general, the rate of
      synonymous substitution is too high to discern related repeats. Specific
      exceptions provide insight into gene relationships. The observed nucleotide
      relationships are consistent with previously described models involving gene
      duplications followed by both unequal crossing-over and gene conversion events.

PMID- 7713443
TI  - Evolution of ribosomal DNA (rDNA) genetic structure in colonial Californian
      populations of Avena barbata.
AB  - DNA samples from 980 plants of Avena barbata from 48 ecologically diverse sites
      in California and Oregon were assayed to determine their genotype for two
      duplicated loci governing rDNA variants. More than 40 different rDNA genotypes
      were observed among which 5 made up 96% of our sample in environmentally
      homogeneous sites; predominant genotypes were less frequent and recombinant
      genotypes were more frequent in environmentally heterogeneous sites. The spatial
      distribution of each predominant rDNA genotype was nearly an exact overlay on
      both macro- and microgeographical scales of a distinctive habitat and also of the
      distribution of an eight-locus morphological-allozyme variant genotype. In all,
      seven different habitat-genotype combinations (ecotypes) were distinguishable on
      the basis of their morphological-allozyme-rDNA genotypes. None of these seven
      genotypes has been found in ancestral Spanish populations; thus the above
      predominant multilocus genotypes (ecotypes) of the colonial populations evidently
      evolved subsequent to the recent introduction (within 150-200 generations) of A.
      barbata to California. The precise associations of specific alleles and genotypes
      of the morphological allozyme and rDNA loci with different specifiable habitats
      leads us to the conclusion that natural selection favoring particular multilocus
      combinations of alleles in different habitats was the main guiding force in
      shaping the internal genetic structure of local populations as well as the
      overall adaptive landscape of A. barbata over California and Oregon.

PMID- 7713444
TI  - Pollen fertility restoration by nuclear gene Fr in CMS bean: nuclear-directed
      alteration of a mitochondrial population.
AB  - Two nuclear genes, Fr and Fr2, have been identified that restore pollen fertility
      to cytoplasmic male sterile (CMS) common bean (Phaseolus vulgaris L.) by
      apparently distinct mechanisms. Whereas Fr2 appears to suppress the expression of
      a male sterility associated mitochondrial sequence (designated pvs), Fr restores
      pollen fertility by causing the elimination of this unusual mitochondrial DNA
      segment. To further investigate the mechanism of Fr action, Fr and Fr2 were
      cointroduced into the nucleus of a bean line containing the sterility inducing
      cytoplasm. When the effect of pvs was suppressed by Fr2, the presence of Fr no
      longer directed the elimination of the mitochondrial pvs sequence. This result
      suggests that the Fr function is dependent on proper expression of the pvs
      sequence. To evaluate the temporal and spatial patterns of Fr action, we
      undertook a polymerase chain reaction-based approach to trace the fate of the pvs
      sequence in different tissues of F2 and F3 fertile-restored plants derived from a
      genetic cross between a cytoplasmic male sterile line of common bean, CMS-Sprite
      (frfr), and fertility restorer line R351 (FrFr). We demonstrate that the Fr
      directed disappearance of pvs sequence occurs during flower development.
      Elimination of the pvs sequence from developing megaspores results in permanent
      fertility restoration in the following generations. Genetic analysis demonstrated
      that permanent fertility restoration, that is, the complete elimination of pvs
      from reproductive tissues requires two doses of the Fr allele or the absence of
      fr in F2 individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713445
TI  - Molecular genetics of growth and development in populus. IV. Mapping QTLs with
      large effects on growth, form, and phenology traits in a forest tree.
AB  - We have mapped quantitative trait loci (QTLs) for commercially important traits
      (stem growth and form) and an adaptive trait (spring leaf flush) in a Populus F2
      generation derived from a cross between interspecific F1 hybrids (P. trichocarpa
      x P. deltoides). Phenotypic data were collected over a 2-year period from a
      replicated clonal trial containing ramets of the parental, F1, and F2 trees.
      Contrary to the assumptions of simple polygenic models of quantitative trait
      inheritance, 1-5 QTLs of large effect are responsible for a large portion of the
      genetic variance in each of the traits measured. For example, 44.7% of the
      genetic variance in stem volume after 2 years of growth is controlled by just two
      QTLs. QTLs governing stem basal area were found clustered with QTLs for sylleptic
      branch leaf area, sharing similar chromosomal position and mode of action and
      suggesting a pleiotropic effect of QTLs ultimately responsible for stem diameter
      growth.

PMID- 7713447
TI  - A space-time process model for the evolution of DNA sequences.
AB  - We describe a model for the evolution of DNA sequences by nucleotide
      substitution, whereby nucleotide sites in the sequence evolve over time, whereas
      the rates of substitution are variable and correlated over sites. The temporal
      process used to describe substitutions between nucleotides is a continuous-time
      Markov process, with the four nucleotides as the states. The spatial process used
      to describe variation and dependence of substitution rates over sites is based on
      a serially correlated gamma distribution, i.e., an auto-gamma model assuming
      Markov-dependence of rates at adjacent sites. To achieve computational
      efficiency, we use several equal-probability categories to approximate the gamma
      distribution, and the result is an auto-discrete-gamma model for rates over
      sites. Correlation of rates at sites then is modeled by the Markov chain
      transition of rates at adjacent sites from one rate category to another, the
      states of the chain being the rate categories. Two versions of nonparametric
      models, which place no restrictions on the distributional forms of rates for
      sites, also are considered, assuming either independence or Markov dependence.
      The models are applied to data of a segment of mitochondrial genome from nine
      primate species. Model parameters are estimated by the maximum likelihood method,
      and models are compared by the likelihood ratio test. Tremendous variation of
      rates among sites in the sequence is revealed by the analyses, and when rate
      differences for different codon positions are appropriately accounted for in the
      models, substitution rates at adjacent sites are found to be strongly
      (positively) correlated. Robustness of the results to uncertainty of the
      phylogenetic tree linking the species is examined.

PMID- 7713448
TI  - Classification and etiology of nasal defects.

PMID- 7713449
TI  - Aesthetic and anatomic considerations for nasal reconstruction.

PMID- 7713446
TI  - A generalized least-squares estimate for the origin of sporophytic self
      incompatibility.
AB  - Analysis of nucleotide sequences that regulate the expression of self
      incompatibility in flowering plants affords a direct means of examining classical
      hypotheses for the origin and evolution of this major feature of mating systems.
      Departing from the classical view of monophyly of all forms of self
      incompatibility, the current paradigm for the origin of self-incompatibility
      postulates multiple episodes of recruitment and modification of preexisting
      genes. In Brassica, the S locus, which regulates sporophytic self
      incompatibility, shows homology to a multigene family present both in self
      compatible congeners and in groups for which this form of self-incompatibility is
      atypical. A phylogenetic analysis of S-allele sequences together with homologous
      sequences that do not cosegregate with self-incompatibility permits dating the
      change of function that marked the origin of self-incompatibility. A generalized
      least-squares method is introduced that provides closed-form expressions for
      estimates and standard errors for function-specific divergence rates and times of
      divergence among sequences. This analysis suggests that the age of the
      sporophytic self-incompatibility system expressed in Brassica exceeds species
      divergence within the genus by four- to fivefold. The extraordinarily high levels
      of sequence diversity exhibited by S alleles appears to reflect their ancient
      derivation, with the alternative hypothesis of hypermutability rejected by the
      analysis.

PMID- 7713450
TI  - Functional rhinoplasty.

PMID- 7713451
TI  - Local flaps for nasal reconstruction.

PMID- 7713452
TI  - Regional and distant flaps in nasal reconstruction.

PMID- 7713453
TI  - The use of grafts in nasal reconstruction.

PMID- 7713454
TI  - Reflections on total and near total nasal reconstruction.

PMID- 7713455
TI  - Prosthetics in nasal reconstruction.

PMID- 7713456
TI  - Modified universal tiplasty: closed structure rhinoplasty as it pertains to the
      overprojected and the broad tip.

PMID- 7713457
TI  - The Biosure Study: influence of composition of diet and food consumption on
      longevity, degenerative diseases and neoplasia in Wistar rats studied for up to
      30 months post weaning.
AB  - The 1200-rat Biosure Study had six interrelated aims: (1) To see whether dietary
      restriction (80% ad lib.) reduces the age-standardized incidence of fatal or
      potentially fatal neoplasia before the age of 30 months. (2) To see whether the
      beneficial effects of diet restriction can be achieved by (a) limiting the daily
      period of access to food to 6 hr, or by (b) limiting the energy value of the
      diet. (3) To see whether reduced calorie intake between weaning and age 4 months
      influences survival and/or incidence of non-neoplastic and neoplastic diseases.
      (4) To compare effects of food consumption, energy intake and protein intake on
      survival and disease. (5) To study the relationships between body weight at
      different ages with eventual survival and disease incidence. (6) To provide a
      database for studying relationships between various in-life measurements and
      eventual survival and disease incidence in individual animals. Twelve groups of
      SKF Wistar rats consisting of 50 animals of each sex were fed according to
      different dietary regimens from when they were weaned at the age of 3 wk until
      they died, or had to be killed because they were sick, or until the experiment
      was terminated at 30 months. For five of the 12 dietary regimens, satellite
      groups consisting of 30 animals per sex were maintained in parallel and used to
      supply information on the effect of diet on circulating hormone levels during the
      course of the study. During the 13 wk post weaning a Standard Breeder diet (SB)
      was provided either ad lib. (four groups), 80% ad lib. (three groups), or with
      access to food limited to 6 hr per day (one group). During this same period two
      other groups were fed a Low Nutrient Breeder diet (LB) ad lib. A further group
      was fed a Low Nutrient Maintenance (high fibre) diet (LM) ad lib. Finally, one
      group was fed the high protein Porton Rat diet (PR) ad lib.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7713458
TI  - Drug accumulation and elimination in Calliphora vicina larvae.
AB  - Calliphora vicina larvae were fed on drug-laden muscle from three suicides
      involving amitriptyline, temazepam and a combination of trazodone and
      trimipramine; triplicate daily harvestings were analysed. The limit of detection
      for all four drugs was 0.01 micrograms drug/g larvae. Mean drug concentrations
      (microgram/g) in the initial muscle were:amitriptyline, 2.68; temazepam, 4.04;
      trazodone, 21.56; and trimipramine, 19.58. Larval rearings for days 4-8 (15
      larval samples per drug) had mean and ranges of drug concentrations (microgram/g)
      of 0.10 (r, 0.02-0.24) for amitriptyline; 0.52 (r, 0.26-0.78) for temazepam; 0.13
      (r, 0.05-0.32) for trazodone; and 0.28 (r, 0.10-0.59) for trimipramine. After day
      8 there was a precipitous fall in larval drug concentrations associated with
      pupariation. At day 11 ranges of drug concentrations (microgram/g) were:
      amitriptyline, < 0.01-0.01; temazepam, 0.01-0.08; trazodone, < 0.01-0.01; and
      trimipramine, 0.04-0.04. Day 16 pupae had corresponding ranges (microgram/g) of <
      0.01, 0.01-0.01, < 0.01 and < 0.01-0.02. Transfer to drug-free food at day 5 led
      to similar falls in drug concentrations (microgram/g) from day 5 to day 6: 0.08
      0.03 for amitriptyline, 0.61-0.09 for temazepam, 0.13-0.01 for trazodone, and
      0.30-0.02 for trimipramine. The results show considerable variation in larval
      drug concentrations, both at the same developmental stage and at different stages
      of the life cycle, under conditions which closely reflect case situations. In
      practice, the precipitous decrease in drug concentrations in non-feeding larvae
      and at pupariation make it desirable to sample only larvae actively feeding on a
      corpse.

PMID- 7713459
TI  - Computer-assisted simulation of conventional roentgenograms from three
      dimensional computed tomography (CT) data--an aid in the identification of
      unknown corpses (FoXSIS).
AB  - A computer simulation program (Forensic X-ray Simulation and Identification
      System, FoXSIS) is presented. FoXSIS calculates conventional X-ray summation
      images using any scanning parameters from three-dimensional CT data records. All
      those parameters decisive for X-ray morphology are freely selectable for
      realistic simulations: focus-object distance, object-film distance, centering of
      the X-ray beam, the location of the object in the patch of rays, brightness and
      contrast, as well as parallel and central projection. In addition, distance and
      angle measurements, as well as enlargements of details are possible. The program
      may be expected to help in the identification of unknown corpses now, and even
      more in the future on account of the increased use of clinical computed
      tomographies.

PMID- 7713460
TI  - Identification of human skeletal muscle from a tissue fragment by detection of
      human myoglobin using a double-sandwich ELISA.
AB  - A method for identifying human skeletal muscle by detection of human myoglobin
      using a double-sandwich ELISA was developed. When an extract was prepared from
      0.1 g skeletal muscle homogenized with 10 ml PBS, this method was able to detect
      human myoglobin in extracts diluted 10(4)-fold. There was no difference in the
      detection limit between individuals or sites of origin of skeletal muscles.
      Species specificity was good and no cross reaction occurred with skeletal muscle
      from other animals except the gorilla. Our method could also discriminate between
      skeletal muscle and other organs or tissues except the heart. Human myoglobin
      could be detected in skeletal muscles under the following conditions: putrefied
      at room temperature for 5 months, dried at room temperature for 11 months, heated
      at 100 degrees C for 72 h and immersed in fresh water at room temperature for 6
      days. Two practical cases to which this method was applied are presented.

PMID- 7713462
TI  - Concerning the article by D.W.K. Cotton et al., entitled: "Are hip fractures
      caused by falling and breaking or breaking and falling? Photoelastic stress
      analysis" (Forensic Sci. Int., 65 (1994) 105-112)

PMID- 7713461
TI  - Chiral identification and determination of ephedrine, pseudoephedrine,
      methamphetamine and methcathinone by gas chromatography and nuclear magnetic
      resonance.
AB  - The enantiomers of the related substances methamphetamine, ephedrine,
      pseudoephedrine and methcathinone were determined by both gas chromatography
      after derivatization and by nuclear magnetic resonance using a chiral solvating
      agent. For GC the substances were derivatized with (R)-(+)-alpha-methoxy-alpha
      (trifluoromethyl)phenylacetic acid (MTPA) to give diasteromeric derivatives.
      Resolution (baseline) of at least 1.6 was obtained between all derivatives. NMR
      determination of the enantiomers was conducted in a chiral environment by the
      addition of the chiral solvating agent, (R)-(+)-1,1'-bi-2-naphthol, to NMR
      solutions of the substances. Racemization of methcathinone was demonstrated to be
      facile by exposure to alkaline solutions for varying periods of time.
      Enantiomeric ratios of some products derived from the oxidation of ephedrine were
      determined.

PMID- 7713463
TI  - [Natural healing for heart failure. Natural healing series, 2: Stage I and II
      heart failure].

PMID- 7713464
TI  - [Radiotherapy for prevention of postoperative periarticular calcinosis. Using
      fractionated irradiation after total endoprosthesis of the hip joint].
AB  - According to the Literature, and confirmed by our own experience, fractionated
      postoperative radiation administered after total hip replacement can, with a high
      degree of reliability (13 out of 14 patients), prevent postoperative
      ossification. At least in the case of elderly patients beyond the age of
      procreation, it is superior to alternative therapeutic measures (biphosphonates,
      prostaglandin synthesis inhibitors).

PMID- 7713465
TI  - [Neurotoxicity of aluminum. Study of a long-term exposed sample of workers of an
      aluminum powder industry].
AB  - Within the framework of a transverse study, the mental performance of a group of
      subjects exposed to aluminium over many years (n = 32; aluminium powder industry)
      was compared with that of a structurally similar control group (n = 30).
      Neuropsychological and electrophysiological tests revealed no signs of cognitive
      performance, despite aluminium burdening. Aluminium levels in plasma and urine
      were elevated.

PMID- 7713466
TI  - [Do we need the concept of male climacteric?].
AB  - The female menopause is considered to be a result of a decrease in the endocrinal
      metabolic activity of the ovaries. Although the male lacks such a highly visible
      sign as the cessation of the menstrual flow, the amount of testosterone produced
      by the aging male does in fact decrease. Recent studies, such as the
      Massachusetts Male Aging Study show that, between the ages of 40 to 70 years, the
      mean testosterone level decreases annually by about 1%. Chronic diseases and the
      use of drugs have a comparable effect. Although it is generally believed that
      sexual impotence is a major symptom of male menopause, recent investigations have
      shown that sexual functionability may be preserved into the ninth and tenth
      decade of life. Sexuality is not merely an instinct or a psychological
      expression, but is deeply anchored within the personality. Even when, with
      increasing age, the frequency of sexual dysfunction increases, such changes do
      not correlate with the decrease in testosterone levels. None of these phenomena
      take place within an age span that marks them off from the involution processes
      in other organs. The expression midlife crisis commonly met with in the English
      literature points up the psycho-social implications. Impotence or a loss of
      sexuality is not a sequel of aging, but of attitude towards sexuality. The latter
      is preserved if it is not neglected throughout the course of a lifetime.

PMID- 7713467
TI  - [Enzyme therapy--an alternative in treatment of herpes zoster. A controlled study
      of 192 patients].
AB  - PROBLEM: Herpes Zoster requires an effective, inexpensive form of treatment not
      only because it impairs quality of life, but also on account of its relatively
      high incidence and the resulting costs incurred. Given the present situation in
      the health care sector, the high costs of treatment with the standard drug,
      acyclovir, often mean that herpes zoster patients do not receive medicinal
      therapy. AIM: The aim of the present study was to establish whether the positive
      results of a prior investigation involving treatment with an enzyme combination
      preparation could be confirmed. METHOD: Over a period of 14 days, two groups of
      96 patients each were given acyclovir or an enzyme combination preparation.
      During the course of the study, the intensity (score) of segmental pain and
      various skin lesions were investigated. RESULTS: In terms of the first end point,
      "segmental pain", the test groups showed no significant difference either on day
      7 or on day 14. Although the second end point "segmental reddening" did reveal a
      significant difference (p = 0.015) in favor of the acyclovir group on day 14, no
      significant difference was found for any of the other examination endpoints. Nor
      did any of the other skin lesions evaluated differ significantly by the end of
      the study. CONCLUSIONS: Overall, the enzyme combination preparation showed
      identical efficacy with acyclovir. The results of the prior study were thus
      confirmed. Further investigations on the immunomodulatory potency, dosage and
      effects on postherpetic herpes neuralgia are, however, still required.

PMID- 7713468
TI  - [How reliable are tumor markers? Only the experienced physician knows how to
      apply these diagnostic aids sensibly].

PMID- 7713469
TI  - Practical questions about therapy of hypertension with ACE inhibitors. J.
      Scholze, Berlin, on the 24-hour effect, possible combinations and side-effects of
      ACE inhibitors--ASS/antirheumatic agents.

PMID- 7713471
TI  - [HbA1 values: reliable or a gamble?].

PMID- 7713470
TI  - [Alternative delivery in the bath tub: risk of infection for babies?].

PMID- 7713472
TI  - [A genetic test for breast cancer: curse or blessing?].

PMID- 7713473
TI  - [Insulin resistance and arterial hypertension].
AB  - Insulin resistance and reactive hyperinsulinemia occur not only in patients with
      obesity, impaired glucose tolerance or non-insulin-dependent (Type 2) diabetes
      mellitus, but also in many non-obese, non-diabetic individuals with essentiell
      hypertension and their normotensive, lean young offsprings. The common
      coexistance of a genetic predisposition for hypertension with insulin resistance
      helps to explain the frequent occurrence of hypertension as well as dyslipidemia,
      obesity and diabetes Type 2 in a given individual. In the pathogenesis of
      hypertension, inappropriate vasoconstriction and/or a structural vasculopathy
      appears to be an important and ultimate causative event. Several pressor
      mechanisms are discussed and a distinct sodium retention appears to be almost
      obligatory associated with diabetes mellitus, while essential and particularly
      obesity-associated hypertension involves predominantly a tendency for sympathetic
      activation. Acute hyperinsulinemia on one hand causes arterial vasodilation and
      on the other hand enhances renal sodium reabsorption and sympathetic activity.
      Chronically, hyperinsulinemia may promote cardiovascular muscle cell
      proliferation and atherogenesis. Insulin resistance affecting certain
      transmembrane cation transporters might lead to an elevation of intracellular
      cytosolic calcium levels thereby inducing inappropriate vasoconstriction.
      Nevertheless, whether insulin resistance and hyperinsulinemia contribute to the
      pathogenesis of hypertension per se is still unproven. Considering
      antihypertensive drugs, thiazide diuretics given in medium or high dosage as well
      as beta-blockers appear to promote insulin resistance, reactive hyperinsulinemia
      and dyslipidemia. Almost all calcium antagonists and the conventional
      sympthatolytics are metabolically neutral, while ACE-inhibitors and alpha 1
      blockers tend to improve insulin resistance. In Type 2 diabetic patients, ACE
      inhibitors exert in addition to their antihypertensive a potentially useful anti
      diabetic effect. Nevertheless, the prognostic relevance of the metabolic side
      effects of antihypertensive drugs awaits further clarification.

PMID- 7713474
TI  - Metabolic syndrome as a cardiovascular risk factor.

PMID- 7713476
TI  - [Abdominal obesity and coronary heart disease. Pathophysiology and clinical
      significance].
AB  - The relationship between overweight and cardiovascular disease was a matter of
      debate for many years. Recent studies have demonstrated that obesity defined as
      body mass index of 30 kg/m2 or higher is associated with an exponential increase
      of cardiovascular complications. This effect is largely mediated by the induction
      of established risk factors such as dyslipidemia, hypertension and type 2
      diabetes mellitus. Recently, there is growing evidence that the occurrence of
      most complications of obesity depends not only on the degree of overweight but
      also on the pattern of body fat distribution. Many data suggest that the
      anatomical localization of body fat is more important for the risk of developing
      complications than the adipose tissue mass per se. An abdominal, upper-body type
      of fat distribution, which can be easily determined by the measurement of waist
      and hip circumferences (waist/hip ratio = WHR), is also a confirmed risk factor
      for metabolic disturbances, hypertension and atherosclerosis, independent of body
      weight. However, the clinical appearance of these disturbances is frequently
      associated with the development of obesity. This network of metabolic disorders
      and their vascular complications is termed "metabolic syndrome" or "syndrome X"
      (Table 2). Abdominal obesity is now known to be closely associated with the
      metabolic syndrome and is regarded to represent its readily recognizable
      phenotypic feature. The components of the metabolic syndrome are characterized by
      varying forms and degrees of insulin resistance. It is assumed that insulin
      resistance, defined as diminished biological response to the action of insulin,
      represents the primary defect or at least the common pathogenetic link between
      these disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713475
TI  - [Disorders of lipid metabolism in insulin resistance].
AB  - Insulin resistance with consecutive hyperinsulinemia is associated with
      dyslipidemia in individuals with metabolic syndrome or "syndrome x". This
      dyslipidemia is characterized by a hypertriglyceridemia and reduced levels of HDL
      (high density lipoprotein)cholesterol in plasma. Table 1 summarizes the
      alterations of lipoproteins in insulin resistance. In severe forms of insulin
      resistance LDL-(low density lipoprotein)cholesterol can be elevated as well. The
      hypertriglyceridemia is caused by an elevated synthesis and secretion of VLDL
      (very low density lipoprotein) in the liver and by reduced metabolism, mediated
      e.g. by lipoprotein lipase. The alterations of VLDL-metabolism are associated
      with a reduced concentration of HDL-cholesterol. In addition the composition of
      lipoprotein particles can be altered, which might interfere with their normal
      metabolism. Furthermore addition direct effects of insulin on cellular
      cholesterol metabolism have been described. These alterations in lipid metabolism
      which are due to an insulin resistance and hyperinsulinemia might be related to
      the increased coronary risk which has been observed in patients with metabolic
      syndrome. Therefore the diagnostic approach in patients with hypertriglyceridemia
      should consider the possibility of an underlying glucose intolerance or Type 2
      diabetes. Therapeutic aims and strategies are discussed. In accordance to
      guidelines of the American Heart Association the goals of lipid-lowering therapy
      take into account the prevalence of various cardiovascular risk factors in an
      individual patient (Table 2). Principle actions of lipid-lowering drugs on plasma
      lipids are outlined in Table 3. Table 4 summarizes the effect of antihypertensive
      drugs on plasma lipids and lipoproteins, which should be considered in the
      treatment of patients with dyslipidemia.

PMID- 7713477
TI  - [Pathophysiology of insulin resistance].
AB  - Insulin resistance of skeletal muscle, liver and fat combined with an abnormality
      of insulin secretion characterizes Type 2 (non-insulin-dependent) diabetes
      mellitus. There is increasing evidence that the insulin resistance of the
      skeletal muscle plays a key role early in the development of Type 2 diabetes. As
      a consequence recent research efforts have focussed on the characterization of
      insulin signal transduction elements in the muscle which are candidates for a
      localization of a defect causing insulin resistance, i.e. the insulin receptor,
      phosphatases related to insulin action, glycogen synthase and the glucose
      transporters. In this review we attempt to summarize present knowledge about
      abnormalities of these systems in skeletal muscle of Type 2 diabetic and pre
      diabetic individuals. We try to classify abnormalities as secondary events or as
      candidates for putative primary molecular defects which might initiate the
      development of insulin resistance as early as in the "pre-diabetic" state.
      Insulin resistance is combined with abnormalities of insulin secretion.
      Compensatory hypersecretion of insulin is typically found in early stages of the
      development of the "Metabolic Endocrine Syndrome" and the pre-diabetic state. The
      transition from this pre-diabetic state to the clinically overt Type 2 diabetes
      is accompanied or even caused by declining insulin secretion. The molecular
      mechanism causing declining insulin secretion is not understood in detail. Beside
      genetically determined factors regulatory events might be important.

PMID- 7713479
TI  - Histopathology of gastroduodenal inflammation: the impact of Helicobacter pylori.
AB  - In this article the histological features of acute and chronic gastritis are
      reviewed. The histopathological gastric biopsy report can now encompass an
      aetiological, topographical (when antrum and corpus are sampled) and
      morphological comment on the gastric mucosa. The degree of detail included in the
      report (e.g. grading of the severity of inflammation, atrophy, density of
      Helicobacter pylori) will vary according to local requirement. However, the
      distinct recognisable patterns of inflammation categorised in the Sydney system
      provide a common terminology for a succinct diagnosis. The overall condition of
      the patient's gastric mucosa assigns him/her to one of the H. pylori-positive or
      negative categories of chronic gastritis. This may not only have relevance to
      current clinical management, but may be a valuable record if the patient returns
      with dyspeptic symptoms in the future. For example, duodenal ulcers are unlikely
      to develop except in patients with antrum predominant H. pylori-associated
      gastritis. Knowledge of the natural history of different types of gastritis is
      rapidly evolving, and the biopsy provides a permanent 'snapshot' of the state of
      the gastric mucosa at the time of the endoscopy.

PMID- 7713478
TI  - [Non-pharmacological therapy of metabolic syndrome].
AB  - The metabolic syndrome usually goes along with abdominal obesity: diabetes type
      II, hypertension, dyslipidemia, and gout are often associated. The common
      characteristic is the resistance to insulin action. Reasons for the metabolic
      syndrome are--besides a genetic determination--overnutrition, physical
      inactivity, and alcohol consumption. Therefore, a causal therapy aims at the
      elimination of these factors. Consequently, the non-pharmacological therapy of
      the metabolic syndrome should be emphasized. The most important treatment is the
      reduction of body weight in the presence of obesity which is relevant for almost
      90% of the patients. Body weight can rapidly be diminished by hypocaloric diets.
      Both, conventional reducing diets or formula diets may be used for weight
      reduction. Total fasting should not be performed for several reasons. For minor
      weight reduction or weight maintenance following a period of rapid weight loss
      with a hypocaloric diet, increased physical activity also lowers weight or
      prevents relapsing. Aims of therapeutical procedures are the elimination or
      amelioration of insulin resistance and subsequently the diseases of the metabolic
      syndrome. Both methods, reducing diet and physical training, act on various
      factors related to insulin resistance. For example, hypocaloric diets activate
      thyroxine kinase of the insulin receptor and reduce glucose and insulin in
      plasma. Physical training reduces not only insulin and glucose in plasma but also
      free fatty acids in addition and increases capillary density in skeletal muscle.
      Using the glucose clamp technique, diets and training are equally effective in
      improving glucose metabolism. Compared to these non-pharmacological methods drugs
      are less convincing. Since the non-pharmacological treatment implies behavioral
      changes with regard to nutrition, physical activity and alcohol consumption,
      simple instructions are not sufficient. Usually long-lasting changes in life
      style are necessary in order to achieve health improvement. Therefore, health
      care programs on individual or social basis are required in order to improve
      nutrition and increase physical activity. However, long-acting effects are
      difficult to achieve in adults; more promising is the prevention of insulin
      resistance.

PMID- 7713480
TI  - Mantle cell lymphoma: a clinicopathological study of 55 cases.
AB  - A recently described unifying proposal for mantle cell lymphoma has led to the
      formulation of strict diagnostic criteria based on morphology, immunology and
      molecular data to define this specific entity. Previous studies were often based
      on broader definitions such as centrocytic lymphoma, intermediately
      differentiated lymphoma or mantle zone lymphoma and, therefore, included a
      variety of entities with some, but not all, features ascribed to the mantle cell
      lymphoma. Since the publication of the unifying proposal no comprehensive studies
      have been published to confirm and support it. We selected 55 cases of mantle
      cell lymphoma collected in our institution in order to evaluate the validity of
      the proposal and, by using strict criteria, we analysed the morphological
      features, their variations and the changes occurring in the course of the disease
      as well as its clinical behaviour. The analysis of this material demonstrates
      that mantle cell lymphoma affects predominantly elderly males presenting with an
      advanced stage of disease. Twenty-four out of 55 patients died with, or of, the
      disease with a median survival of 32 months, even though most of them received
      aggressive chemotherapy. In all cases the histological features were strikingly
      uniform and most cases had a diffuse growth pattern. The neoplastic cells
      corresponded to small cleaved cells with a minimal variation in shape and size
      from one case to the other. The phenotype of the neoplastic cells was remarkably
      constant with expression of several pan-B cell markers, IgM, IgD and CD5, and
      lack of CD10 and CD23.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713481
TI  - Primary cutaneous sarcomas showing rhabdomyoblastic differentiation.
AB  - Rhabdomyosarcoma is a rare soft tissue neoplasm most commonly encountered in
      childhood and adolescence which has a predilection for the head and neck area,
      the genito-urinary tract and the extremities. Primary cutaneous presentation is
      extremely unusual and has been rarely reported in the literature. Herein, we
      describe two cases of rhabdomyosarcoma arising in the dermis of a 9-year-old girl
      and an 86-year-old man. Clinically, the tumours presented as solitary plaque-like
      or nodular lesions confined to the skin of the nose and chest wall, respectively.
      Histologically, the tumour in the first patient corresponded to an embryonal
      rhabdomyosarcoma. The tumour recurred locally four times, and in the last
      recurrence, showed features resembling those of malignant 'triton' tumour with
      fascicles of S-100 protein-positive spindle cells admixed with the
      rhabdomyoblastic components. The tumour in the second patient corresponded to the
      solid variant of alveolar rhabdomyosarcoma. Immunohistochemical studies in both
      tumours showed positive labelling for muscle-specific actin, desmin and vimentin.
      Ultrastructural examination in one case showed clusters of intermediate filaments
      in the cytoplasm recapitulating abortive sarcomeric structures consistent with
      rhabdomyoblastic differentiation. Both patients developed repeated recurrences
      over a period of 2-4 years despite adequate surgical excision, and the second
      patient had an axillary lymph node metastasis. Primary cutaneous rhabdomyosarcoma
      should be considered in the evaluation of small 'blue cell' tumours or
      undifferentiated malignant neoplasms of the skin, and appropriate
      immunohistochemical studies in conjunction with electron microscopy should be
      employed for proper evaluation of such lesions.

PMID- 7713482
TI  - Association between mucosal hyperplasia of the appendix and adenocarcinoma of the
      colon.
AB  - Mucosal hyperplasia of the appendix is a seemingly benign change of poorly
      understood significance, at times found in patients with colorectal malignancy.
      To determine the incidence of this change and its association with colonic
      adenocarcinoma, we have examined the appendiceal mucosa in 122 ileocolectomy
      specimens gathered between 1987 and 1990, and in 273 consecutive appendectomies
      carried out during 1990 at The Methodist Hospital in Houston, Texas. We found
      that 23 out of 122 ileocolectomies (18.8%) showed mucosal hyperplasia of the
      appendix and, of these, 17 (77%) were associated with colorectal malignancy,
      predominantly of the right side. Moreover, 24 of 273 appendectomies (8.8%)
      exhibited the presence of mucosal hyperplasia and, of these, six (25%) also were
      associated with adenocarcinoma of the colon. On the basis of this significant
      rate of association, we feel that a concomitant colorectal carcinoma should be
      ruled out in patients who exhibit mucosal hyperplasia of the appendix.

PMID- 7713483
TI  - The histopathology of human melioidosis.
AB  - We examined human tissues infected by Burkholderia (Pseudomonas) pseudomallei
      which is endemic in Malaysia to study the types of inflammation invoked, and to
      look for histopathological clues to its diagnosis. The lesions which varied from
      acute to chronic granulomatous inflammation were not tissue-specific. In five
      autopsy cases, the inflammation was usually a focal or diffuse, acute necrotising
      inflammation with varying numbers of neutrophils, macrophages, lymphocytes and
      'giant cells'. The 'giant cells' probably represent giant macrophages with
      phagocytosed leukocytes. There were numerous gram-negative, non-acid-fast, intra-
      and extracellular bacilli, occurring either singly or in chains. Intracellular
      bacteria within macrophages and 'giant cells' were so numerous as to resemble
      globi. This feature has not been previously reported and may be a useful
      diagnostic clue in melioidosis. In 14 surgical cases biopsies showed acute
      inflammatory lesions that appeared no different from acute inflammation due to
      other causes. In many biopsies, however, the inflammation was either an acute-on
      chronic inflammation with a focal granulomatous component, or was purely
      granulomatous in character. Bacilli were difficult to demonstrate in surgical
      biopsies even with the gram strain.

PMID- 7713485
TI  - p53 immunoreactivity in hepatocellular adenoma, focal nodular hyperplasia,
      cirrhosis and hepatocellular carcinoma.
AB  - The prolonged half-life of mutant p53 makes feasible its immunocytochemical
      detection. In order to assess the pathogenetic role of mutant p53 in regenerative
      and neoplastic liver disease we studied its immunohistochemical expression in
      cases of hepatic cirrhosis, hepatocellular carcinoma (HCC), cirrhosis with areas
      of HCC, hepatocellular adenoma and focal nodular hyperplasia. The study included
      needle and wedge biopsies of 50 cirrhotic livers, 59 HCCs (36 of them with
      associated cirrhosis), six adenomas and two focal nodular hyperplasias. Sixty
      five HCC fine-needle cytology specimens were also included in the study. There
      was no immunohistochemical evidence of mutant p53 expression in any of the cases
      of cirrhotic liver (except for one instance associated with HCC) adenoma or focal
      nodular hyperplasia. In contrast p53 was detected in 8.5% of HCC cases in the
      biopsy series and 24% of HCC cases in the fine needle aspiration series. In
      addition, mutant p53 expression in HCC was positively correlated with tumour
      grade. According to grade, the distribution of p53 positive immunoreactivity
      among HCCs was as follows: Grade I-II, 0% of cases in the biopsy series and 9% in
      the fine needle aspirates; Grade III, 18% in the biopsy series and 55% in the
      fine needle aspirates; and Grade IV, 40% in the biopsy series. Therefore, mutant
      p53 expression does not seem to be associated with benign liver lesions but seems
      to correlate with the progression of HCC through various grades of increasing
      malignancy.

PMID- 7713484
TI  - Are infantile myofibromatosis, congenital fibrosarcoma and congenital
      haemangiopericytoma histogenetically related?
AB  - Infantile myofibromatosis, congenital fibrosarcoma and congenital/infantile
      haemangiopericytoma are generally considered distinct entities. Overlapping
      microscopic features between infantile myofibromatosis and congenital
      fibrosarcoma, and between infantile myofibromatosis and congenital/infantile
      haemangiopericytoma, however, have been noted, but not formally reported. This
      report concerns six neonatal tumours, each exhibiting more than one of the above
      patterns, supporting a histogenetic relationship among these entities.
      Immunohistochemistry for smooth muscle actin was found to be useful in the
      diagnosis of congenital/infantile haemangiopericytoma, and also served to support
      a histogenetic relationship with the other two entities under consideration.

PMID- 7713486
TI  - Heterogeneity of bcl-2 expression in MALT lymphoma.
AB  - Bcl-2 protein expression was studied in a series of 58 MALT lymphomas using a
      monoclonal antibody which recognises this protein in routinely processed paraffin
      embedded tissue. Thirty-three of 58 cases showed heterogeneity for bcl-2
      expression, 18 of 58 cases were bcl-2 positive and 7 of 58 were bcl-2 negative.
      High grade and low grade MALT lymphomas showed different patterns of staining.
      All 21 low grade tumours were positive for bcl-2, though in seven cases only a
      proportion of the neoplastic cells expressed this protein. In the 37 high grade
      tumours the majority of the neoplastic cells were negative with seven cases
      showing no reactivity at all. These findings give further support to the theory
      that MALT lymphomas differ in pathogenesis to nodal lymphomas and suggest that
      the good prognosis of MALT lymphomas may partly be explained by the fact that
      they maintain a normal pattern of bcl-2 expression.

PMID- 7713487
TI  - Leishmaniasis of the larynx.

PMID- 7713488
TI  - Pleural pearls following silicosis: a histological and electronmicroscopic study.

PMID- 7713489
TI  - What is the value of bcl-2 protein detection for histopathologists?

PMID- 7713490
TI  - Classification of primary cutaneous T-cell lymphomas.

PMID- 7713491
TI  - Characterization of 10 new polymorphic dinucleotide repeats and generation of a
      high-density microsatellite-based physical map of the BRCA1 region of chromosome
      17q21.
AB  - A familial early onset breast cancer gene (BRCA1) has been localized to
      chromosome 17q21. To aid in the identification of this gene a number of new
      microsatellite markers from the D17S857 to D17S78 region were isolated and
      characterized. These markers, along with previously published markers from the
      region, were localized on a physical map by STS content mapping of cosmids from
      the BRCA1 interval. This high-density STS map of the BRCA1 region will be useful
      for linkage studies of families with apparent inherited breast cancer and for
      loss of heterozygosity analysis of breast tumor DNAs.

PMID- 7713492
TI  - Fine mapping of Best's macular dystrophy localizes the gene in close proximity to
      but distinct from the D11S480/ROM1 loci.
AB  - The Best's macular dystrophy (BMD) gene has previously been mapped to the 11q13
      region. In this study, recombination data localizes the BMD gene to the 6-cM
      genetic interval between the markers Fc epsilon RI and D11S480/ROM1 in a large
      Swedish 12-generation BMD family. Mutation analyses of the candidate gene ROM1
      did not reveal any mutations that could explain the disease phenotype. However,
      one recombination event between intragenic ROM1 polymorphisms and the BMD
      phenotype was detected. Therefore, it is highly unlikely that mutations in the
      ROM1 gene cause BMD. Identification of the disease gene will elucidate the
      pathophysiological mechanism in BMD, which may also be of importance in other
      retinopathies such as age-related macular degeneration.

PMID- 7713494
TI  - Chromosomal location and some structural features of human clathrin light-chain
      genes (CLTA and CLTB).
AB  - Two human clathrin light-chain genes have been defined. The gene (CLTA) encoding
      the LCa light chain maps to the long arm of chromosome 12 at 12q23-q24 and that
      encoding the LCb light chain (CLTB) maps to the long arm of chromosome 4 at 4q2
      q3. Isolation and characterization of partial genomic clones encoding human LCa
      and LCb reveal the neuron-specific insertions of the LCa and LCb proteins to be
      encoded by discrete exons, thus proving that clathrin light chains undergo
      alternate mRNA splicing to generate tissue-specific protein isoforms. The
      insertion sequence of LCb is encoded by a single exon and that of LCa by two
      exons. The first of the two neuron-specific LCa exons is homologous to the
      corresponding LCb exon. An intronic sequence of the LCb gene with similarity to
      the second neuron-specific exon of the LCa gene has been identified.

PMID- 7713493
TI  - Characterization of human and mouse cartilage oligomeric matrix protein.
AB  - Cartilage oligomeric matrix protein (COMP) is a 524,000-Da protein that is
      expressed at high levels in the territorial matrix of chondrocytes. The sequences
      of rat and bovine COMP indicate that it is a member of the thrombospondin gene
      family. In this study, we have cloned and sequenced human COMP. Phylogenetic
      analysis using progressive sequence alignment and two parsimony-based algorithms
      indicates that the COMP gene and a precursor of the thrombospondin-3 and -4 genes
      were produced by a gene duplication that occurred 750 million years ago. An
      interspecific backcross mapping panel has been used to map the murine COMP gene
      to the central region of mouse chromosome 8. Southern blot analysis of a somatic
      cell hybrid DNA panel and in situ hybridization to human metaphase chromosomes
      indicate that the human COMP gene is located on chromosome 19 in band p13.1.
      These data confirm and extend the known regions of homology between human and
      mouse chromosomes and establish that COMP, like thrombospondin-1, -2, -3, and -4,
      is present in the human and mouse genomes.

PMID- 7713495
TI  - The human Met-ase gene (GZMM): structure, sequence, and close physical linkage to
      the serine protease gene cluster on 19p13.3.
AB  - Cosmid clones containing the genes for the human and murine natural killer cell
      serine protease Met-ase (gene symbol GZMM; granzyme M) were identified by
      screening human and murine cosmid libraries with rat Met-ase (RNK-Met-1) cDNA.
      The human gene has a size of 7.5 kb and an exon-intron structure identical to
      that of serine protease genes located on human chromosomes 5q11-q12, 14q11.2, and
      19p13.3 that are expressed by lymphocytes, mast cells, or myelomonocyte
      precursors. Using cosmid DNA as a probe for fluorescence in situ hybridization,
      we identified the chromosomal position of human Met-ase as 19p13.3. Interphase
      studies with two differentially labeled probes for Met-ase and the azurocidin
      (AZU1), proteinase 3 (PRTN3), and neutrophil elastase (ELA2) gene cluster
      revealed that the distance of Met-ase from this gene cluster is in the range of
      200 to 500 kb. Using differentially labeled mouse cosmid probes, we also mapped
      the murine gene for Met-ase to chromosomal band 10C, close to the gene for lamin
      B2. Thus, the Met-ase, AZU1, PRTN3, and ELA2 genes fall into an established
      region of homology between mouse chromosomal band 10C and human 19p13.3.

PMID- 7713496
TI  - Enhanced access to rare brain cDNAs by prescreening libraries: 207 new mouse
      brain ESTs.
AB  - To use single-pass cDNA sequencing to characterize low-frequency cDNA clones from
      a region of the brain that includes the primary site of neurodegeneration in
      human Parkinson disease, we have developed a prescreening procedure using single
      brain region first-strand cDNA probes. Selection of cDNA clones giving low
      hybridization signals allowed the elimination of clones resulting from abundant
      messages and enrichment for clones corresponding to low-copy messages.
      Comparative sequencing of standard and prescreened cDNA libraries (191 and 124
      clones, respectively) showed that this procedure raised the frequency of novel
      sequences encountered from 54 to 81%. The increased proportion of novel ESTs
      justifies the labor of prescreening. Automation of this procedure will accelerate
      the molecular description of genes expressed in any brain region, or any tissue,
      and represents a way to maximize access to cDNA sequences for human and mouse
      genome characterization. In total, the comparative sequencing experiments
      generated 207 new mouse and 11 new rat brain ESTs.

PMID- 7713497
TI  - Structure and expression of the human lysyl hydroxylase gene (PLOD): introns 9
      and 16 contain Alu sequences at the sites of recombination in Ehlers-Danlos
      syndrome type VI patients.
AB  - Lysyl hydroxylase (EC 1.14.11.4) catalyzes the formation of hydroxylysine in
      collagens by the hydroxylation of lysine residues in peptide linkages. This
      enzyme activity is known to be reduced in patients with the type VI variant of
      the Ehlers-Danlos syndrome, and the first mutations in the lysyl hydroxylase gene
      (PLOD) have recently been identified. We have now isolated genomic clones for
      human lysyl hydroxylase and determined the complete structure of the gene, which
      contains 19 exons and a 5' flanking region with characteristics shared by
      housekeeping genes. The constitutive expression of the gene in different tissues
      further suggests that lysyl hydroxylase has an essential function. We have
      sequenced the introns of the gene in the region where many mutations and
      rearrangements analyzed to date are concentrated. Intron 9 and intron 16 show
      extensive homology resulting from the many Alu sequences found in these introns.
      Intron 9 contains five and intron 16 eight Alu sequences. The high homology and
      many short identical or complementary sequences in these introns generate many
      potential recombination sites with the gene. The delineation of the structure of
      the lysyl hydroxylase gene contributes significantly to our understanding of the
      rearrangements in the genome of Ehlers-Danlos type VI patients.

PMID- 7713498
TI  - Molecular cloning, cDNA sequence, and chromosomal localization of the human
      phosphatidylinositol 3-kinase p110 alpha (PIK3CA) gene.
AB  - Phosphatidylinositol (PI) 3-kinase is a heterodimeric enzyme comprising a 110-kDa
      catalytic subunit and an 85-kDa regulatory subunit that binds to tyrosine
      phosphopeptide sites linked directly or indirectly to receptors serving diverse
      signal functions. Knowledge of the structure and function of PI 3-kinase was
      greatly advanced by the purification, cDNA cloning, and subsequent expression of
      the bovine enzyme. Here the cloning of the cDNA for the human p110 alpha subunit
      of PI 3-kinase (PIK3CA), encoding a protein 99% identical to the bovine p110, and
      of its gene in YAC is described. The chromosomal localization of the gene for
      PIK3CA is shown to be at 3q21-qter as determined using somatic cell hybrids. In
      situ hybridization performed using Alu-PCR from the YAC DNA located the gene in
      3q26.3.

PMID- 7713499
TI  - Large human YACs constructed in a rad52 strain show a reduced rate of chimerism.
AB  - Current YAC libraries are plagued by a high frequency of chimeras--that is,
      clones containing fragments from multiple genomic regions. Chimeras are thought
      to arise largely through recombination in the yeast host cell. If so, the use of
      recombination-deficient yeast strains, such as rad52 mutants, might be expected
      to alleviate the problem. Here, we report the construction of megabase-sized
      human YACs in the rad52 strain MHY5201 and the determination of their rate of
      chimerism by fluorescence in situ hybridization analysis. Examination of 48 YACs
      showed a rate of chimerism of at most 8%, whereas YACs constructed in the
      wildtype host AB1380 showed a rate of about 50%. These results show that it is
      possible to significantly decrease the rate of YAC chimerism through the use of
      appropriate yeast host strains.

PMID- 7713501
TI  - The structure and organization of the human erythroid anion exchanger (AE1) gene.
AB  - The AE1 (anion exchanger, band 3) protein is expressed in erythrocytes and in the
      A-type intercalated cells of the kidney distal collecting tubule. In both cell
      types it mediates the electroneutral transport of chloride and bicarbonate ions
      across the lipid bilayer, and, in erythrocytes, it also serves as the critical
      attachment site of the peripheral membrane skeleton. We have characterized the
      human AE1 gene using overlapping clones isolated from a phage library of human
      genomic DNA. The gene spans approximately 20 kb and consists of 20 exons
      separated by 19 introns. The structure of the human AE1 gene corresponds closely
      with that of the previously characterized mouse AE1 gene, with a high degree of
      conservation of exon/intron junctions, as well as exon and intron nucleotide
      sequences. The putative upstream and internal promoter sequences of the human AE1
      gene used in erythroid and kidney cells, respectively, are described. We also
      report the nucleotide sequence of the entire 3' noncoding region of exon 20,
      which was lacking in the published cDNA sequences. In addition, we have
      characterized 9 Alu repeat elements found within the body of the human AE1 gene
      that are members of 4 related subfamilies that appear to have entered the genome
      at different times during primate evolution.

PMID- 7713500
TI  - Genomic structure and chromosome location of the human mutT homologue gene MTH1
      encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion.
AB  - 8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is produced by active
      oxygen species in the nucleotide pool of the cell and can be incorporated into
      cellular DNA. Human cells contain enzyme activity that hydrolyzes 8-oxo-dGTP to 8
      oxo-dGMP, thereby preventing occurrence of mutations, caused by misincorporation.
      When the cDNA for human 8-oxo-dGTPase was expressed in Escherichia coli mutT-
      mutant cells devoid of self 8-oxo-dGTPase activity, the elevated level of
      spontaneous A:T to C:G mutation frequency reverted to normal. We isolated the
      genomic sequence encoding the enzyme and named the gene MTH1 (for mutT human
      homologue). This gene is composed of at least 4 exons, spans approximately 9 kb,
      and is located on human chromosome 7p22.

PMID- 7713502
TI  - Similar origins of two mouse minisatellites within transposon-like LTRs.
AB  - Tandem arrays of simple sequence repeat units are among the most unstable regions
      of mammalian genomes. Mutational instability at such loci depends on both repeat
      unit sequence and DNA sequences external to the tandem array, which have been
      recently implicated in polarized variability at human minisatellites. The
      characteristics of DNA sequences flanking the mouse minisatellite Ms6-hm have
      been investigated. This locus has a high mutation rate both in the germline and
      during early somatic development and is composed of a hypervariable tandem array
      of 500-2000 pentanucleotide repeat units flanked by a transposon-like long
      terminal repeat sequence of the mouse transcript (MT) family. A subpopulation of
      MT elements in the mouse genome are shown to flank a 1.1-kb internal sequence,
      consistent with their classification within a newly defined mammalian
      retrotransposon-like superfamily (MaLR). A second mouse minisatellite, Hm-2, also
      originates from within a MaLR LTR. Hm-2 is related to Ms6-hm in repeat unit
      sequence and profiles of germline and somatic instability; at both loci the
      tandem array has amplified from precisely the same point within the LTR. The
      similar origins of Ms6-hm and Hm-2 suggest that flanking MaLR sequences may be
      involved in mutational processes at these loci.

PMID- 7713503
TI  - Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for
      msh2 mutations.
AB  - Hereditary nonpolyposis colorectal carcinoma (HNPCC) is a major cancer
      susceptibility syndrome known to be caused by inheritance of mutations in genes
      such as hMSH2 and hMLH1, which encode components of a DNA mismatch repair system.
      The MSH2 genomic locus has been cloned and shown to cover approximately 73 kb of
      genomic DNA and to contain 16 exons. The sequence of all the intron-exon
      junctions has been determined and used to develop methods for analyzing each MSH2
      exon for mutations. These methods have been used to analyze two large HNPCC
      kindreds exhibiting features of the Muir-Torre syndrome and demonstrate that
      cancer susceptibility is due to the inheritance of a frameshift mutation in the
      MSH2 gene in one family and a nonsense mutation in the MSH2 gene in the other
      family.

PMID- 7713504
TI  - Construction and characterization of a human chromosome 2-specific BAC library.
AB  - We have constructed a human chromosome 2-specific bacterial artificial chromosome
      (BAC) library using DNA from the somatic cell hybrid GM10826. The average size of
      the clones is about 63 kb. The coverage and distribution of the library were
      estimated by screening with known polymorphic genetic markers and fluorescence in
      situ hybridization (FISH). Twenty-one markers tested positive when DNA pools
      prepared from approximately one-sixth of the library were screened with 33 known
      markers. This is consistent with the theoretical calculation of 63% coverage at
      one genomic equivalent. This suggested that the coverage of the library is
      approximately 5-6x. FISH analysis with 54 BACs revealed single site hybridization
      to chromosome 2, and the clones were distributed randomly on the chromosome. We
      have also performed direct sequencing of the BAC insert ends to generate sequence
      tagged sites suitable for mapping and chromosome walking. This is the first
      reported human chromosome 2-specific BAC library and should provide a resource
      for physical mapping and disease searching for this chromosome.

PMID- 7713505
TI  - Molecular cloning and localization of the human GAX gene to 7p21.
AB  - The GAX homeobox gene is expressed in the cardiovascular tissues of the adult
      rat, including heart, lung, kidney, and blood vessels. In the vasculature it is
      specifically expressed in quiescent smooth muscle cells, but its expression is
      rapidly down-regulated when these cells are stimulated to proliferate with
      mitogens. Since vascular smooth muscle cell proliferation is important in the
      pathology of blood vessel disorders, the human GAX gene was isolated and
      characterized. The human GAX cDNA was obtained by an anchored-PCR approach using
      cDNA templates from cardiovascular tissues and amplification primers designed
      from sequence information of the rat GAX cDNA and the homeodomain-containing exon
      of the human GAX gene. The human and rat GAX gene coding sequences are 98%
      conserved at the amino acid level and 83% conserved at the nucleotide level.
      Similar to rat, the human homolog contains a CAX trinucleotide repeat N-terminal
      to the homeodomain that encodes for a stretch of 17 consecutive histidine or
      glutamine residues. The human GAX locus was mapped by fluorescence in situ
      hybridization to the short arm of chromosome 7 at band p21. The human cDNA
      sequence will be useful for analyses of GAX gene expression in cardiovascular
      diseases.

PMID- 7713506
TI  - The location of a disease-associated polymorphism and genomic structure of the
      human 52-kDa Ro/SSA locus (SSA1).
AB  - Sera from approximately 30% of patients with systemic lupus erythematosus (SLE)
      contain high titers of autoantibodies that bind to the 52-kDa Ro/SSA protein. We
      previously detected polymorphisms in the 52-kDa Ro/SSA gene (SSA1) with
      restriction enzymes, one of which is strongly associated with the presence of SLE
      (P < 0.0005) in African Americans. A higher disease frequency and more severe
      forms of the disease are commonly noted among these female patients. To determine
      the location and nature of this polymorphism, we obtained two clones that span
      8.5 kb of the 52-kDa Ro/SSA locus including its upstream regulatory region. Six
      exons were identified, and their nucleotide sequences plus adjacent noncoding
      regions were determined. No differences were found between these exons and the
      coding region of one of the reported cDNAs. The disease-associated polymorphic
      site suggested by a restriction enzyme map and confirmed by DNA amplification and
      nucleotide sequencing was present upstream of exon 1. This polymorphism may be a
      genetic marker for a disease-related variation in the coding region for the
      protein or in the upstream regulatory region of this gene. Although this RFLP is
      present in Japanese, it is not associated with lupus in this race.

PMID- 7713507
TI  - Regional localization of 188 sequence tagged sites on a somatic cell hybrid
      mapping panel for human chromosome 3.
AB  - Chromosome 3 comprises 7% of the genome and contains at least 210 Mb of DNA. To
      expedite the analysis of this chromosome, we have assembled a somatic cell hybrid
      mapping panel that subdivides human chromosome 3 into 23 intervals using a total
      of 19 hybrids. Hybrids were constructed from 16 patients' cells containing
      chromosome 3 translocations. All of these hybrids selectively retained the
      derivative 3 chromosome. In addition, we utilized 2 radiation-reduced hybrids and
      3 hybrids carrying spontaneous translocations between human chromosome 3 and
      rodent chromosomes. The entire panel has 9 short arm breakpoints that involve
      bands p24.2, p22, p21, p14, and p12 plus a total of 11 long arm breakpoints that
      involve bands q13, q21, q25, q26, and q27. In addition, two cell lines appear to
      have breakpoints at or near the centromere. To date, we have used this panel to
      localize 92 sequences regionally on the short arm, 89 sequences on the long arm,
      and 7 sequences near the centromere. These hybrids are useful tools that allow
      the rapid localization of markers on chromosome 3 and greatly assist other
      mapping efforts.

PMID- 7713508
TI  - A PCR-based genetic map for human chromosome 3.
AB  - Oligonucleotide primers for 125 simple sequence repeat microsatellite-based
      genetic markers have been assayed by polymerase chain reaction (PCR) in the CEPH
      reference family panel. These microsatellites include 101 dinucleotide repeats as
      well as 24 new tetranucleotide repeats. The average heterozygosity of this marker
      set was 72.4%. Genetic data were analyzed with the genetic mapping package
      LINKAGE. A subset of these microsatellite markers define a set of 56 uniquely
      ordered loci (> 1000:1 against local inversion) that span 271 cM. Sixty-seven
      additional loci were tightly linked to markers on the uniquely ordered map, but
      could not be ordered with such high precision. These markers were positioned by
      CMAP into confidence intervals. One hundred thirteen of the microsatellite
      markers were also tested on a chromosome 3 framework somatic cell hybrid panel
      that divides this chromosome into 23 cytogenetically defined regions, integrating
      the genetic and physical maps of this chromosome. The high density, high
      heterozygosity, and PCR format of this genetically and physically mapped set of
      markers will accelerate the mapping and positional cloning of new chromosome 3
      genes.

PMID- 7713509
TI  - A novel family of cathepsin L-like (CTSLL) sequences on human chromosome 10q and
      related transcripts.
AB  - We have isolated a human genomic DNA cosmid clone while screening for the
      cathepsin L gene that, when sequenced, revealed close similarity with but
      significant differences from cDNA sequences that have been reported for cathepsin
      L (CTSL). The clone bears a novel sequence that shows 88% identity to the coding
      regions of the cathepsin L gene and a similar exon arrangement. We have called
      this sequence the "human cathepsin L-like gene 1" (CTSLL1). Translating putative
      exon sequences reveals a single premature stop codon; therefore no functional
      products are likely to arise from this gene. Fluorescence in situ hybridization
      (FISH) studies mapped the clone to chromosome 10q. Somatic cell hybrid mapping
      confirmed the location of CTSLL1 to human chromosome 10 distinct from the
      cathepsin L locus (CTSL) on chromosome 9. Furthermore, the FISH mapping studies
      show that a family of at least three related sequences exists on chromosome 10q,
      similar to the pattern of duplicated glutamate dehydrogenase (GLUD) gene loci
      reported on 10q. Using PCR and sequencing with genomic DNA samples, we have
      identified two additional novel related sequences (CTSLL2 and CTSLL3), and by PCR
      analysis of cDNA samples we have identified corresponding transcripts. Comparison
      of changes between our CTSLL1 sequence and the cathepsin L gene at mutation
      insensitive sites suggests that the two sequences arose from a duplication event
      40-50 million years ago, and therefore at the time of divergence of early
      primates.

PMID- 7713510
TI  - Physical mapping of genetic markers on the short arm of chromosome 5.
AB  - The deletion of the short arm of chromosome 5 is associated with the cri-du-chat
      syndrome. In addition, loss of this portion of a chromosome is a common
      cytogenetic marker in a number of malignancies. However, to date, no genes
      associated with these disorders have been identified. Physical maps are the first
      step in isolating causative genes, and genes involved in autosomal recessive
      disorders are now routinely mapped through the identification of linked markers.
      Extensive genetic maps based upon polymorphic short tandem repeats (STRs) have
      provided researchers with a large number of markers to which such disorders can
      be genetically mapped. However, the physical locations of many of these STRs have
      not been determined. Toward the goal of integrating the human genetic maps with
      the physical maps, a 5p somatic cell hybrid deletion mapping panel that was
      derived from patients with 5p deletions or translocations was used to physically
      map 47 STRs that have been used to construct genetic maps of 5p. These data will
      be useful in the localization of disease genes that map to 5p and may be involved
      in the etiology of the cri-du-chat syndrome.

PMID- 7713511
TI  - Subchromosomal band interval mapping and ordering of DNA markers in the region
      3q26.3-q27 involved in the dup(3q) syndrome.
AB  - The duplication 3q syndrome is characterized by the partial trisomy of a segment
      of the long arm of chromosome 3. This segment, although variable in size,
      includes 3q26.3-q27 as the minimal region of overlap. We have previously used
      patient chromosome breakpoints to select cosmids within this region. In this
      report, we have used two- and three-color fluorescence in situ hybridization on
      metaphase and interphase chromosomes to perform high-resolution cytological
      mapping of the six cosmids identified. The results allowed us to determine the
      centromere-telomere orientation, the order, and the relative distances of the
      markers used. Because some of the markers used are part of the consensus
      chromosome 3 map, our data can be easily integrated with existing mapping
      information about this chromosome. Our data provide a framework for further
      physical mapping studies of this region.

PMID- 7713512
TI  - Genomic sequence of the murine guanylin gene.
AB  - Guanylin, a 15-amino-acid peptide, is an endogenous ligand of the intestinal
      receptor guanylate cyclase-C. After binding to this receptor, guanylin increases
      the intracellular concentration of cyclic GMP and induces chloride secretion. We
      have isolated a genomic clone containing the entire murine guanylin gene. The
      guanylin gene is composed of three exons that span 1700 bp. The first 133
      nucleotides of upstream promoter sequence lack the canonical TATA, CAAT, and SP1
      elements. Guanylin transcription is nearly exclusively limited to the intestine,
      and the presence of guanylin mRNA is greatest in the distal colon and ileum.
      Therefore, characterization of the guanylin promoter is likely to provide another
      paradigm for intestine-specific gene regulation.

PMID- 7713513
TI  - Isolation and regional mapping of 110 chromosome 22 STSs.
AB  - As part of a larger effort to create a complete physical map of the human genome,
      we have developed 110 new STSs specific for human chromosome 22. Clones isolated
      and sequenced from chromosome 22-enriched libraries provided a source of primers.
      These STSs were localized to regions of chromosome 22 using a panel of somatic
      cell hybrids. In building a refined physical map of chromosome 22, this set of
      STSs should provide a substantial backbone.

PMID- 7713515
TI  - Mapping of the pulmonary surfactant SP5 (SFTP2) locus to 8p21 and
      characterization of a microsatellite repeat marker that shows frequent loss of
      heterozygosity in human carcinomas.
AB  - We have identified 4 cosmids at the SFTP2 locus by cDNA hybridization. SFTP2 was
      mapped using a polymorphic CA repeat and localized to 8p21 by FISH. Allele loss
      in carcinomas was detected using this PCR marker. Among 11 lung and colon tumors,
      6 of 9 informative cases exhibited allelic loss.

PMID- 7713514
TI  - Spot mapping on the standard profile of restriction landmark genomic scanning
      (RLGS) of sorted chromosome 20 using methylation-insensitive enzyme.
AB  - We established the spot mapping system on a restriction landmark genomic scanning
      (RLGS) profile using sorted chromosome as RLGS material. In this mapping system,
      we can mapped RLGS spots physically, regardless of their polymorphism, using
      methylation-insensitive enzymes in all RLGS steps. Here, we report that we
      identified 28 spots derived from human chromosome 20 on an RLGS profile, and that
      number was in good agreement with the number predicted from the length of the
      chromosome 20.

PMID- 7713516
TI  - The mouse gene encoding the GM2 activator protein (Gm2a): cDNA sequence,
      expression, and chromosome mapping.
AB  - The GM2 activator protein forms a substrate-complex with GM2 ganglioside, which
      enables degradation of the ganglioside by beta-hexosaminidase A. Mutations in the
      human GM2 activator protein gene (GM2A) result in the GM2 gangliosidosis AB
      variant, a severe neurological disease. We have isolated and sequenced a mouse
      GM2 activator protein (Gm2a) cDNA with complete protein coding and 3'
      untranslated regions. Expression of the Gm2a transcript (approximately 2.3 kb)
      was apparent in all tissues examined and was most abundant in kidney and testis.
      The Gm2a gene was mapped to a region on mouse chromosome (Chr) 11 that is
      homologous with a segment of human chromosome 5 containing the orthologous human
      gene. In addition, a Gm2a-related sequence (Gm2a-rs1) was mapped to mouse Chr 5.

PMID- 7713517
TI  - Localization of the adenine nucleotide translocase gene ANT2 to chromosome Xq24
      q25 with tight linkage to DXS425.

PMID- 7713519
TI  - Cloning of the human skeletal muscle alpha 1 subunit of the dihydropyridine
      sensitive L-type calcium channel (CACNL1A3).

PMID- 7713518
TI  - Localization of the human gene for advanced glycosylation end product-specific
      receptor (AGER) to chromosome 6p21.3.

PMID- 7713521
TI  - No increase in female recombination frequency in the distal part of the human
      pseudoautosomal region.

PMID- 7713520
TI  - Assignment of the human caltractin gene (CALT) to Xq28 by fluorescence in situ
      hybridization.

PMID- 7713523
TI  - Assignment of the human dihydropyrimidine dehydrogenase gene (DPYD) to chromosome
      region 1p22 by fluorescence in situ hybridization.

PMID- 7713522
TI  - Integration of 28 STSs into the physical map of human chromosome 18.

PMID- 7713525
TI  - Relationships between yeasts and primary root-caries lesions.
AB  - A total of 447 primary root-caries lesions from 169 dental patients was studied
      to determine the relationships between their clinical severity and the number and
      frequency of isolation of yeasts. Yeasts were isolated more frequently from soft
      lesions, from lesions at the gingival margin and from lesions deemed to require
      restoration. These associations may be due to the aciduricity and acido- genicity
      of yeasts but the relatively low numbers found do not support a pathogenic role
      for yeasts in the aetiology of root caries: at best they may be marker organisms
      of the most severe disease.

PMID- 7713524
TI  - The SHB adaptor protein maps to human chromosome 9.

PMID- 7713527
TI  - Future directions for root caries research.
AB  - Interest among researchers in the diagnosis, aetiology, prevention, and treatment
      of root caries has increased substantially over the past two decades. However,
      there are some fundamental problems impeding the advancement of the field which
      remain to be addressed and resolved. A universally acceptable definition of root
      caries is not yet available. The relationship of root caries to coronal caries
      has not been established. The underlying disease process is still not clearly
      understood. The optimal utilisation of preventive/therapeutic agents for the
      treatment or prevention of root caries has not been determined. New treatment
      materials and preventive agents have not yet been tested in controlled clinical
      trials. These are a few of the issues and problems which we address in this
      paper.

PMID- 7713526
TI  - The effectiveness of oral hygiene programmes for elderly people--a review.
AB  - Comprehensive oral health care is an essential feature of quality of life. In the
      near future, a greater number of elderly people will retain more natural teeth,
      whether or not supplemented by prosthetic provisions, and/or may be provided with
      implants. As a consequence, oral self-care will be much more demanding.
      Prevention must reduce the greater risk of oral disease for elderly people.
      Effective early intervention strategies are: promotion of over-all general
      health, obviation of stereotypes, education by dental hygienists, instruction and
      demonstration combined with systematic evaluation, use of a fluoride containing
      dentifrice, and regular professional support and use of chlorhexidine rinses for
      less well and confused elderly.

PMID- 7713528
TI  - Epidemiology of root caries.
AB  - Many epidemiological studies have been conducted on a variety of populations.
      Unfortunately, comparison of the prevalence data, and to a lesser degree of the
      incidence data, between the various studies is of little use due to the lack of
      standardised diagnostic criteria, reporting methods and population diversity. In
      the few incidence studies which have been conducted around 30-40% of people
      developed root caries, although many adults in the population appear to have been
      affected by root caries. Many risk factors associated with the occurrence of root
      caries have been identified and these include oral, medical, mental, behavioural
      and psychosocial conditions.

PMID- 7713529
TI  - The prevalence of root surface caries amongst Irish adults.
AB  - In a national survey of adult dental health conducted in the Republic of Ireland
      in 1989/90 a total of 1,527 subjects aged 25 and older were examined for root
      surface caries. It was found that the prevalence of root surface caries was
      highest in older age groups and also amongst males, residents of non-fluoridated
      communities and those earning low incomes. Tooth loss masked the potential
      prevalence of root surface caries. With more persons retaining their natural
      teeth into middle and old age the prevalence of root surface caries is likely to
      increase in the future.

PMID- 7713530
TI  - Caries incidence in patients with dementia.
AB  - One in ten persons over the age of 65 and as many as half the population aged 85
      and over have Alzheimer's disease. Review of the literature reveals substantial
      decrements in oral health in persons with dementia as measured by denture
      hygiene, coronal decayed, missing and filled teeth, filled teeth (cervical),
      percentage of the population with caries, Oral Hygiene Index-simplified, and of
      sites with plaque, gingival bleeding and calculus. A study of caries incidence is
      described in 23 male veterans with moderate and advanced dementia of the
      Alzheimer's type, using a comparison group of male veterans from the Department
      of Veterans Affairs Dental Longitudinal Study, matching 2:1 for age, number of
      teeth and education. Baseline findings indicate significant differences in the
      numbers of coronal surfaces with decay, root decayed and/or filled teeth and root
      decayed and/or filled surfaces. Mean annual increments of coronal caries in the
      dementia group were 2.29 +/- 4.29 per 100 surfaces at risk, over twice that in
      the comparison group (0.88 +/- 1.14). For root caries, mean annual increments in
      the dementia group were 2.38 +/- 5.57 per 100 available surfaces, versus 0.31 +/-
      0.69 in the comparison group. Despite these large mean differences, the marked
      variability in these small samples statistical significance in caries increments
      between the two groups. The article concludes by suggesting some potential
      modifications to clinical trials of caries preventive agents and some overall
      research issues in populations with dementia.

PMID- 7713531
TI  - Root caries incidence and associated risk factors in middle-aged and older
      adults.
AB  - Data from population-based longitudinal studies required to assess the incidence
      of root caries and associated risk factors are sparse in the literature. To this
      end, a group of 130 middle-aged and older adults were examined for root caries at
      baseline and at a follow-up visit between nine and 24 months (median: 16 months).
      Dental examinations were conducted by one examiner at a Tufts dental clinic using
      NIDR defined diagnostic criteria. Fifty percent of subjects in this study
      population developed one or more new root caries lesions over the follow-up
      period. Also, an annualised increment of 0.60 (SD: 0.72) decayed and filled
      surfaces per person was observed for the 45-59 year old group while the 70+ group
      showed an annualised increment of 1.38 (SD: 1.97) DFS in this study. Multivariate
      logistic regression analysis identified past root caries experience, high plaque
      score, and high number of teeth (> = 22) to be positively associated with new
      root caries (p < 0.05).

PMID- 7713532
TI  - Predictors of caries in old age.
AB  - This study measured the incidence of dental caries for one year and identified
      factors associated with the risk of caries in a sample of 156 elderly subjects.
      The subjects were examined at baseline and after one year to record the number of
      missing, filled and decayed teeth, to measure oral hygiene and flow of saliva,
      and to estimate the numbers of Streptococcus mutans and Lactobacilli cultured
      from samples of saliva. All subjects were interviewed on both occasions for
      information on their use of medications and dental services and on their
      ingestion of sugar. At baseline the elders had a mean of 19 natural teeth with 5
      decayed surfaces (DS), 38 filled surfaces and a mean Plaque Index (PI) of 1. The
      independent group, on average, had more teeth and fillings but a lower PI and
      less caries. At the end of the year more than two-thirds (71%) of the 98
      institutionalised subjects and over half (59%) of the 58 independent subjects had
      at least one new decayed/filled surface (DFS). The mean net DFS increment per
      subject was 4.6 and 2.0 respectively. Regression analyses on multivariate models
      identified caries at baseline, residence in long term care facilities, high
      numbers of Lactobacilli, poor oral hygiene and frequent sugar consumption as the
      variables contributing most significantly to the risk of caries in old age.

PMID- 7713533
TI  - Relationships between mutans streptococci and perceived treatment need of primary
      root-caries lesions.
AB  - A total of 447 primary root-caries lesions from 169 dental patients was studied
      to determine the relationships between mutans streptococci and the perceived
      treatment need of primary root-caries lesions. Samples of this altered dentine
      for microbiological culture were obtained. Lesions were classified into 5
      treatment categories: soft and restore, leathery and restore, leathery and
      debride of caries, leathery and treat chemotherapeutically, and hard, to receive
      no treatment. The total numbers of mutans streptococci decreased significantly
      with decreased treatment need. The percentage of mutans streptococci from lesions
      requiring no treatment was significantly less than from lesions requiring
      treatment. The frequency of isolation of mutans streptococci was significantly
      greater from lesions requiring more treatment. Significantly more lesions
      containing > 10(2) mutans streptococci were distributed in the groups with a
      greater perceived treatment need or with larger dimensions occluso-gingivally
      and/or mesio-distally or bucco-lingually or with a closer proximity to the
      gingival margin.

PMID- 7713534
TI  - Whither Gerodontology: a specialty, specialism or what?

PMID- 7713535
TI  - Planning oral health care for the elderly in Israel for the years 2000 and 2025.
AB  - The methodology and conclusions of this workshop are reported here because the
      problems requiring solution are not unique to Israel. They will increasingly have
      wide geographical and political application. The population of Israel since its
      establishment in 1948 has increased about sixfold. The numbers of the elderly
      (65+) have increased about tenfold. The current situation must be examined and
      estimates obtained for the next ten years. Only thus can the system be enabled to
      cope with the problem as it develops. The chosen method was a carefully
      preplanned, multisectorial workshop. Recommendations were discussed, amended and
      finalised. The recommendations of the workshop included: Baseline national data
      is urgently required. Guidelines are required for selecting specific target
      populations to which priority should be given. The current favourable situation
      of adequate oral health manpower in Israel makes it possible to encourage
      providers of oral health care towards treatment for the elderly. It is essential
      that the appropriate health authorities allocate sufficient funds for the
      following urgent purposes: the conduct of a national survey of the elderly
      population; the establishment of oral health units on a trial basis in some
      selected hospitals; support institutions of higher education to facilitate
      training in geriatric dentistry. CONCLUSIONS. The workshop was multidisciplinary
      because it was necessary to include all the expertise and experience available as
      vital elements of the policy making process. This type of workshop was found to
      be an effective tool for planning oral health services.

PMID- 7713536
TI  - Infective endocarditis and the dental practitioner.
AB  - This article reviews the relationship of dental treatment to infective
      endocarditis (IE). The current guidelines on the use of antibiotics in
      prophylaxis are also examined.

PMID- 7713537
TI  - Oral care of people with disability: a qualitative exploration of the views of
      nursing staff.
AB  - This study aimed to identify influences, attitudes and actions of nursing staff
      in relation to oral care for people with disabilities. Individual in-depth
      interviews of twenty two nursing staff were conducted. Enabling and inhibiting
      factors in the reported attitudes, approaches and practices were identified. The
      main enabling factors were that nursing staff saw mouth care as part of their
      role and took an empathic and caring approach to its delivery. They aimed to make
      the residents socially acceptable, improve their self-esteem and make their
      mouths clean and breath fresher. Inhibiting factors were: a lack of training,
      time constraints associated with workload, and poor understanding of the
      processes causing dental disease. The study concludes that improvements in oral
      care by nursing staff can be encouraged by working with nurses' attitudes, values
      and beliefs. Once the desired behaviour change has occurred then the lack of
      knowledge can be addressed.

PMID- 7713538
TI  - The perceived importance of appearance and oral function, comfort and health for
      severely demented persons rated by relatives, nursing staff and hospital
      dentists.
AB  - Dental health is an aspect of the quality of life. Oral treatment goals for, the
      severely demented and the benefits of oral treatment are complex issues. Severely
      demented people can neither express their wishes nor make rational decisions
      about oral care. Acting "in the best interests" of a demented person who refuses
      or does not understand the purpose of treatment depends on what perspective and
      treatment priorities the advocate has. For oral treatment of a demented person
      the advocate may be a relative, a member of the ward staff or a hospital dentist.
      In a structured interview, the relatives of demented patients in a Stockholm
      hospital and members of the nursing staff were asked to rate the importance of
      goals for dental care. These ratings were also recorded for hospital dentists. In
      this study there was agreement on the importance of freedom from oral pain and
      fear of aspiration. Nursing personnel gave priority to aspects of good care such
      as being able to chew and enjoy eating. Relatives were also concerned with social
      behaviour and communication such as fresh breath, normal speech, and normal
      appearance. The ratings by the hospital dentists were generally lower which might
      reflect professional awareness of the limitations of treatment success implied by
      cognitive impairment.

PMID- 7713539
TI  - A study of some masticatory functions in 90-year old subjects.
AB  - A group of 35 90-year old subjects, randomly selected from the gerontologic
      population study in Goteborg (H-70), were examined with respect to function and
      dysfunction of the masticatory system. The methods included a questionnaire,
      clinical examination and recording of bite force endurance and maximal bite
      force, measured in the central incisor region. Forty percent were edentulous, 29%
      were partially edentulous and wore a removable denture, while the others were
      dentate without removable prostheses. Signs and symptoms of temporomandibular
      disorders were mostly mild and infrequent, except TMJ crepitation which was
      recorded in 69% of the subjects. Maximal bite force was in general low (mean 94
      N) but showed a great individual variation (range 10 to 410 N). Bite force
      endurance was also very variable (mean 72 s, range 10 to 205 s). None of the 35
      subjects reported poor masticatory ability, but 2 said they could not chew all
      kinds of food. In spite of a reduced bite force this group of 90-year olds
      considered their masticatory ability as good and most of them had no severe signs
      and symptoms of temporomandibular disorders.

PMID- 7713540
TI  - EMG study on the effect of ageing on the human masseteric jaw-jerk reflex.
AB  - The effect of age on the masseteric jaw-jerk reflex was investigated in 22 young
      (11 males and 11 females with mean age 23.2 years) and 22 older dentate subjects
      (11 males and 11 females with mean age 61.3 years). Electromyographic (EMG)
      recordings were obtained, after chin taps, from the relaxed masseter muscle of
      the preferred chewing side, by use of a computerised recording and analysis
      system. With increasing age the occurrence of the reflex was reduced, the latency
      was increased, while the amplitude was decreased. Those findings are probably
      related to the general age related changes in the muscular tissue, the sense
      organs, the peripheral nerves and especially the central nervous system.
      Increased biological variance was also observed in the older subjects, as in most
      aspects of performance in the latent years. Furthermore, the effects of ageing
      were generally similar in men and women. The age-related decrement in the
      monosynaptic reflex response is indicative of a generalised decline in the motor
      performance of the stomatognathic system and the decreased ability of the older
      dental patient to easily adapt to any dramatic changes in the sensory input.

PMID- 7713541
TI  - The effect of age on the recognition thresholds of three sweeteners: sucrose,
      saccharin and aspartame.
AB  - It is believed that people's sensitivity to taste declines with age but the
      evidence is inconclusive. This study was designed to test the hypothesis that
      taste recognition thresholds (TRTs) for sweetness are higher in older than in
      younger individuals, using groups of 16 younger subjects (18-30) and 16 older
      subjects (60-85). Three test substances were used: sucrose, aspartame and
      saccharin. A questionnaire recorded variables which might have affected TRTs, but
      data failed to show any trend that might have biased the principle variate-age.
      There was a significant alteration with age of recognition thresholds, at least
      for sucrose and saccharin. The differences between the groups for the three
      sweeteners were due to the fact that all the very sensitive subjects were young.
      None of the older subjects had particularly poor discrimination: all but one had
      TRTs within the range of younger subjects. Although there are age-related taste
      changes, they are much less dramatic than commonly occurs with other senses, such
      as sight and hearing. The findings of this study have implications for
      institutional catering and the dietary management of older people using non-sugar
      sweeteners.

PMID- 7713543
TI  - Patient age, service mix and dental practice productivity.
AB  - To further explore economic relationships between patient age and dental practice
      productivity detected in previous studies, this study investigated the effects of
      variations in the mix of services used by different age groups on time and dollar
      based dental practice outputs. Production function models for dental services
      were estimated using data from 31 Minnesota general dental practices reporting
      increased visits by older adults between June, 1980 and December, 1984. Analysis
      suggested that standardised time-based measures of productivity were not greatly
      affected by differences in the types of services used by different age groups. In
      contrast, differences in service mix between age groups exerted a substantial
      influence on dollar-based productivity that was independent of patient age.
      Overall, dental practices were less productive with older patients, but the
      decline in monetary productivity was not evident until patient age was
      disaggregated from differences in service use by different age groups.

PMID- 7713542
TI  - The effect of Salinum on the symptoms of dry mouth: a pilot study.
AB  - The effect of a new saliva substitute, Salinum, was tested in 37 patients with
      severe symptoms of reduced salivation. The majority of the patients had suffered
      from hyposalivation and dry mouth for more than 8 years. The saliva substitute
      consisted of a water soluble extract of linseed. The physical properties of this
      extract are similar to those of the glycoproteins of the salivary secretions. The
      patients used the saliva substitute for a seven days period. Prior to the use of
      the extract the patients reported that the most severe symptoms of decreased
      salivation were a feeling of dryness in the mouth and burning sensations in the
      tongue, pharynx and oesophagus, The majority of the patients reported that the
      use of Salinum reduced the symptoms of hyposalivation. Great variation in effect
      occurred from patient to patient. Generally the patients with the most severe
      symptoms experienced the greatest relief of the symptoms when they used Salinum.
      Although of short duration the results of this pilot study indicate that an
      extract of linseeds may compensate for some aspects of the consequences of
      reduced salivation. Further studies are needed to elucidate the feasibility of
      the extract as saliva replacement.

PMID- 7713544
TI  - Age-related satisfaction with complete dentures, desire for improvement and
      attitudes to implant treatment.
AB  - In the edentulous lower jaw implant stabilised dentures have proved clinically so
      successful that the indication for this treatment is now being discussed more
      often with geriatric patients. The aim of this study of edentate subjects was to
      determine the age-relation of the demand for denture improvement, the risks and
      feasibility of implant treatment. Sixty four complete denture wearers aged from
      42 to 84 years took part in the study. A questionnaire was used to determine the
      subjective demand for denture improvement. For 33 subjects implants seemed
      possible. For these patients fear and scepticism concerning implant treatment
      were specified and quantified. Impaired general health was the most frequent
      absolute contra-indication for implants; the local oral prerequisites tended to
      be slightly less favourable in elderly. Older patients were more satisfied with
      poorly fitting dentures and were less prepared to take trouble to achieve denture
      improvement. Although scepticism concerning implant treatment was not age
      related, patients who were keen for an improvement of their dentures were
      significantly younger and less sceptical about implants.

PMID- 7713545
TI  - Robert-Koch-Symposium 1993 on Progress in Tuberculosis Research.

PMID- 7713546
TI  - Tuberculosis: distribution, risk factors, mortality.
AB  - About a century after Koch's discovery of the TB bacilli the tuberculosis
      epidemic which had appeared to be under control was again recognized as a major
      global health threat. The decline in the epidemic in this century had been
      largely through the improved living standards and, eventually, the availability
      and use of effective antibiotics. While tuberculosis gradually disappeared from
      the health agenda in the western world it remained a big killer throughout the
      century and in 1992 an estimated 2.7 million TB deaths occurred; 30 million will
      die from TB during the 1990s if current trends are not reversed. The annual
      number of new cases will increase from 7.5 million estimated in 1990 to more than
      10 million in the year 2000. The main factors for this increase are demographic
      forces, population movements, the HIV epidemic and increasing drug resistance.
      The impact of the HIV epidemic is already felt in many sub-Saharan African
      countries and now threatens Asia where almost two-thirds of the world's TB
      infected population live and where HIV is spreading. Tuberculosis has also
      reemerged as a major public health problem in industrialized countries due to
      international migration, the breakdown of health services, including TB services
      etc. The control of the epidemic can only be through a concerted action to
      reinstate TB as priority among health concerns, reflected in national and
      international resources. A coalition of public and private supporters must be
      mobilized to support the effort to fight the disease. Governments, non
      governmental organizations, the business community, refugee organizations,
      medical institutions, and other UN agencies are invited to join with WHO in this
      effort.

PMID- 7713547
TI  - Epidemiology of tuberculosis: the impact of HIV and multidrug-resistant strains.
AB  - The recent reemergence of tuberculosis in the United States and other developed
      countries has been attributed to a number of factors including a decreased
      emphasis on tuberculosis control and immigration. Perhaps the most significant
      factor is the association of tuberculosis and HIV/AIDS. Infection with HIV
      greatly increases susceptibility to infection and increases the risk of
      developing active disease. In addition, progression of tuberculosis can be very
      rapid in patients with greatly reduced immune function. The increasing incidence
      of drug resistance is also contributing to the difficulty in controlling
      tuberculosis. Multidrug-resistance not only adversely affects the patient but
      contributes to prolonged infectiousness.

PMID- 7713548
TI  - Complicated tuberculosis and residual disease.
AB  - Complicated and extrapulmonary manifestations of tuberculosis (TB) may cause
      prolonged suffering for the individual patient and represent a high economic
      burden for the society concerned. Complications of pulmonary TB may be the
      consequence of reduced individual resistance, immunosuppression or specific
      immune defects. In HIV patients, pulmonary TB is often associated with
      extrapulmonary lesions, while the radiologic appearance of lung infiltrates may
      be less prominent compared to HIV negative persons. The present review summarizes
      data obtained during a 12-year study of extrapulmonary TB in Berlin, Germany, and
      outlines the role of residual TB lesions for disease reactivation in later life.
      Indications and limitations of INH preventive chemotherapy will be discussed.

PMID- 7713549
TI  - Immunohistochemical analysis of cell composition and in situ cytokine expression
      in HIV- and non-HIV-associated tuberculous lymphadenitis.
AB  - Inflammatory cells in lymph nodes of eighteen patients suffering from culture
      proven tuberculous lymphadenitis were examined by histological and
      immunohistochemical techniques. Ten patients suffered from symptomatic HIV
      infection and eight patients were immunocompetent individuals without HIV-1
      serology. Characteristic granulomas with or without caseation were observed in
      eight immunocompetent and four HIV-1-infected patients with less marked
      lymphopenia of CD4 positive peripheral blood lymphocytes. No epitheloid cell
      formation was present in lymph nodes of HIV1-infected patients with more severe
      depression of CD4 positive peripheral blood lymphocyte count. Foamy macrophages
      were found instead of these cells. While many cells--predominantly lymphocytes-
      express CD25 (IL-2 receptor) in cases with typical epitheloid granulomas there is
      no such CD25 expression in cases without any epitheloid cell formation. This
      result suggest that T cell function is necessary for epitheloid granuloma
      formation in human tuberculosis. The phenotype of macrophages underwent
      progressive changes parallel to decreasing numbers of CD4 positive peripheral
      blood lymphocytes. Foamy macrophages in Mycobacterium avium-intracellulare
      infection represented an end-stage phenotype. They were positive for S100 protein
      and they did not express lysozyme, alpha-1-anti-chymotrypsin, L1 antigen (Mac387)
      and CD4, whereas positivity for HLA-DR, CD68 and Ki-M8 was preserved. In situ
      immunohistochemical demonstration of IFN-alpha, IFN-beta, TNF-alpha, IL-1 and IL
      6 revealed that foamy cells in M. tuberculosis infection were highly active
      effector cells. They contained higher concentrations of the examined cytokines
      than epitheloid cells in the lesions of HIV+ and HIV-patients. Corresponding to
      these findings the histological proof of acid-fast bacilli was generally not
      successful in typical HIV-associated tuberculosis. The foamy appearance may
      result from the lipid-rich cell membranes of destroyed acid-fast bacilli. In
      contrast acid-fast bacilli-packed foamy macrophages in AIDS patients with M.
      avium-intracellulare (MAI) infection did not produce any of the examined
      cytokines.

PMID- 7713550
TI  - BCG-induced granuloma formation in murine tissues.
AB  - BCG infection of mice provides a convenient model to study natural and cellular
      immunity to mycobacteria and the mechanisms of granuloma formation and repair. We
      have used a range of macrophage (M phi) membrane molecules and secretory products
      to investigate resident M phi-pathogen interactions and T lymphocyte-dependent
      recruitment and activation of M phi in different tissues of immature, normal
      adult and gamma interferon deficient animals. In situ hybridization (ISH), RT-PCR
      and immunocytochemical analysis of M phi gene and product expression have been
      correlated with in vitro study of endocytic and secretory activity in which
      biogel polyacrylamide bead-elicited peritoneal M phi are exposed to Th1 and Th2
      cytokines, LPS, BCG and other stimuli. The role of resident and newly recruited M
      phi responding to BCG in liver, spleen, lung and brain has been defined by means
      of antigen markers expressed by M phi (F4/80, 7/4, CR3, macrosialin, sialoadhesin
      and scavenger receptor) and/or T and B lymphoid cells (MHC Class II, CD4, CD8,
      B220). Heterogeneity in M phi secretory activity was revealed by ISH analysis of
      lysozyme, TNF-alpha, IL-1 IL-6 and MCP-1, by in vitro assay of NO and superoxide
      anion production, and by RT-PCR studies of Th1 (interferon gamma) and Th2 (IL-4,
      IL-13, IL-10) lymphokine mRNA in tissues. Our studies confirm the importance of
      interferon gamma as a critical mediator of host resistance to mycobacterial
      infection and raise intriguing questions in regard to T cell and M phi functional
      heterogeneity in distinct tissue microenvironments.

PMID- 7713551
TI  - Cytokine patterns at the site of mycobacterial infection.
AB  - Distinct patterns of T cell cytokine production have been shown to influence the
      outcome of infection in mouse models and humans. Th1 or Type 1 cytokines,
      interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) are generally associated
      with resistance to infection, whereas Th2 or Type 2 cytokines, IL-4 and IL-10 are
      associated with progressive disease. Leprosy is a useful model for studying the
      role of cytokines in modulating T cell responses in human infectious disease.
      Infection by Mycobacterium leprae results in disease manifestations that
      encompass an immunological spectrum. Tuberculoid patients are able to restrict
      the growth of the pathogen and mount strong T cell responses to M. leprae. In
      contrast, lepromatous patients manifest disseminated infection and their T cells
      weakly respond to M. leprae. We have found that tuberculoid leprosy lesions have
      a predominance of CD4+ T cells producing the Type 1 cytokine pattern. Secondly,
      IL-12 mRNA was expressed at 10-fold higher levels in tuberculoid lesions as
      compared to lepromatous lesions and that IL-12 promotes the selective expansion
      of the Type 1 cytokine producing cells. In contrast, lepromatous lesions contain
      CD8+ IL-4-producing cells that suppress antigen-specific T cell responses and
      promote the outgrowth of additional suppressor T cells. IL-10, also expressed at
      higher levels in lepromatous as compared to tuberculoid lesions, was found to be
      produced by macrophages, effectively inhibiting cytokine production and
      macrophage activity.

PMID- 7713552
TI  - Mycobacterium leprae DNA content, cellular and cytokine patterns in skin lesions
      of leprosy patients undergoing multidrug therapy (MDT).
AB  - Skin biopsies from untreated and MDT-treated patients were examined for
      infiltrating cells and cells producing the cytokines TNF-alpha, IFN-gamma, and IL
      1 beta using immunohistochemistry. Biopsy specimens from untreated tuberculoid
      leprosy patients were characterized by the presence of cells producing TNF-alpha,
      IFN-gamma, and IL-1 beta and of subepidermal Langerhans cells. These cells were
      rarely found or completely absent in biopsies of untreated lepromatous leprosy
      patients, but tended to increase under MDT. In a short-term therapy trial for
      three months with brodimoprim, dapsone, and rifampicin, 12 patients were
      monitored by follow-up biopsies. Semiquantitative PCR for mycobacterial DNA
      revealed two groups of patients: one group in which mycobacterial DNA in follow
      up biopsies remained constant and a second group in which a decrease of
      mycobacterial DNA during therapy was noted. Immunophenotyping in these follow-up
      biopsies revealed that in the latter group IFN-gamma-positive cells and
      Langerhans cells were present and gamma delta T cell receptor-positive cells
      tended to decrease during therapy. In contrast, in patients whose mycobacterial
      DNA did not change during therapy, these phenotypical manifestations were not
      observed. We therefore, conclude that assessment of mycobacterial DNA in
      combination with phenotyping of infiltrating cells and determination of cytokine
      patterns may be useful tools in establishing criteria for the effectiveness and
      duration of MDT in patients with leprosy.

PMID- 7713553
TI  - Mycobacterial infection in guinea pigs.
AB  - We described published reports of the chaos which exists in research concerning
      laboratory animal models for assay of tuberculosis (TB) vaccines and proposed a
      "rational animal model" as a solution to the problem. This animal model, an
      aerosol challenge model in guinea pigs, was recently applied to the problem of
      differences in growth characteristics of sputum isolates of low and high
      virulence. The same model was used to investigate the protective effect of high
      dose BCG given aerogenically. Based on studies in the guinea pig model of
      experimental airborne TB, and a review of the literature on pathogenesis of human
      TB, we described an "integrated model" for the pathogenesis of TB, a model which
      includes a role for both the endogenous reactivation and the exogenous
      reinfection pathways. Our hypothesis is that tubercle bacilli must be able to
      gain access to the "vulnerable region" in the lung apex in order to survive the
      effects of the CMI response. In endogenous reactivation TB (virulent tubercle
      bacilli), this access occurs via the bloodstream. Whereas in exogenous
      reinfection TB, access to the vulnerable region occurs via multiple exposures via
      the respiratory tract. Central to our perspective is the acceptance of the
      evidence that during first infection with virulent organisms, tubercle bacilli
      enter the bloodstream via the efferent lymphatics. We believe the hypotheses we
      have proposed have the potential to lead to a further increase in our knowledge
      of these mechanisms and are a prerequisite to studies aimed at the development of
      new vaccines.

PMID- 7713554
TI  - Respiratory host defenses--surface immunity.
AB  - The mucosal surface of the respiratory tract has an operable immune system,
      specially designed for producing immunoglobulins (antibodies); however, it has
      not been harnessed effectively yet to provide local, immunospecific protection
      against many microbes that enter. Respiratory host responses in humans have been
      used in this review where possible. New research approaches seem necessary to
      manipulate the physical and immunologic barriers in the respiratory tract and
      this may require different antigen preparations, better and more specific
      vehicles for delivery and selective enhancement of cytokines and interleukins in
      the mucosa. The immunologic tools are available and need to be explored more in
      the human model.

PMID- 7713555
TI  - Transient inducible events in different tissues: in situ studies in the context
      of the development and expression of the immune responses to intracellular
      pathogens.
AB  - Intracellular pathogens whether facultative like Mycobacterium sp., e.g. Bacillus
      Calmette Guerin, Listeria monocytogenes or strictly intracellular like Leishmania
      sp. initiate either asymptomatic infectious processes or disease depending both
      on factors of the host (genetic as well as environmental ones) and the
      infectious/pathogenic agents. In this contribution, we first summarized
      informations which justify to develop in situ analysis to decipher the sequential
      events that result in different modes/classes of immune responses. How the mode
      of the immune response is determined remains a main question to address. Although
      it has recently become clear, in vitro, that immunocompetent cells and their
      cytokines are critical to set on a stable mode of immune response, acting on
      naive T cells, this area deserves more in vivo studies. Indeed, peripheral T
      cells, at different stages of differentiation, may exist in vivo (a)
      naive/virgin, (b) experienced, (c) effector T cells, depending on the level of
      stimulation of the immune system by either endogenous or exogenous (e.g. gut
      flora) signals. The three chosen examples illustrate our contributions in this
      field focusing on three different non-lymphoid tissues which may become infected:
      bone marrow (Bacille de Calmette Guerin), liver (Listeria monocytogenes), skin
      (Leishmania major). These three illustrations also allow to attract attention on
      the interest of using mice of genetically different strains the immune response
      of which is set up under different modes.

PMID- 7713559
TI  - The Bcg gene story.
AB  - The genetic influences on the course of mycobacterial infections during epidemics
      and in endemic areas have always been suspected, but the precise nature of such
      genetic control and of the inherited mechanisms of susceptibility have been
      unknown. We have used methods of population genetics in the mouse to discover a
      single dominant autosomal gene (Bcg), which controls the susceptibility to
      various species of mycobacteria as well as to other intracellular parasites. The
      phenotypic expression of the Bcg gene has been defined as nonspecific macrophage
      activation for bactericidal function, resulting in the destruction of ingested
      intracellular parasites early following infection. Using recombinant inbred
      strains of mice, we have mapped this gene to the centromeric part of chromosome 1
      and we have created a high resolution linkage map and, subsequently, a physical
      map in the close vicinity of this locus. A 400 kb bacteriophage and cosmid contig
      assembled within the genomic interval overlapping Bcg contained six novel
      transcription units. RNA expression studies showed that one of these genes
      (designated Nramp for "natural resistance associated macrophage protein"), was
      expressed exclusively in macrophages. Nramp encodes an integral membrane protein
      that has structural homology with known prokaryotic and eukaryotic transport
      systems, suggesting a macrophage-specific membrane transport function.
      Susceptibility to infection (Bcgs) in 27 Bcgs and Bcgr strains tested is
      associated with a Gly-105 to Asp-105 substitution within predicted transmembrane
      domain 2 of Nramp, making this gene a strong candidate for Bcg. The chromosomal
      segment in the vicinity of the Bcg gene has been conserved in the human genome
      (chromosome 2q). Linkage analysis between the phenotype of disease during a
      tuberculosis outbreak in an extended multisib Canadian Indian family and allelic
      variants of chromosome 2 has revealed a significant LOD score. This finding,
      together with the emerging information on almost total sequence homology between
      the murine and human Nramp genes suggests that this gene may be responsible for
      the phenotype of resistance or susceptibility to tuberculosis.

PMID- 7713558
TI  - The role of cytokines in the formation of the schistosome egg granuloma.
AB  - Schistosomiasis mansoni is a helminth-induced disease infecting over 120 million
      people in the tropics. Morbidity and mortality are caused by parasite eggs that
      evoke in the liver and intestines of infected persons, T cell-mediated
      granulomatous inflammation and irreversible fibrosis. In the murine model
      granulomatous inflammation is induced by CD4+ T helper lymphocytes. This short
      review summarizes recent observations that implicate a variety of lymphokines and
      cytokines as mediators of the granulomatous inflammatory response. Mediator
      production was examined in splenocyte as well as granuloma cell cultures of
      infected or egg granuloma-bearing mice. In the synchronous pulmonary granuloma
      model generated around i.v. injected eggs in naive mice IL-1 mRNA expression and
      IL-1 production were detectable within the first 4 days of granuloma growth.
      After 4-6 days TNF-alpha mRNA message appeared and cytokine production was
      observed. With the aging of the granuloma, production of both cytokines
      diminished. Thus, these cytokines are considered to be the primary recruiters of
      cellular aggregation in granuloma growth. The role of TNF-alpha in granuloma
      formation was also confirmed in infected mice. Whereas treatment of animals with
      anti-TNF-alpha antiserum diminished hepatic granuloma size, repeated injection of
      murine rTNF-alpha into chronically-infected mice enhanced the downmodulated
      granuloma response. With the administration of specific anti-lymphokine mAbs and
      recombinant murine lymphokines, as well as serial assays of lymphokine production
      by splenic, granuloma lymphocytes of infected mice, the role of INF-gamma, IL-2
      and IL-4 was delineated. Interferon-gamma was found to be produced very early at
      the inception of the liver granulomatous response. By the time granulomas reached
      maximal size (8 wks post infection) production declined. Concurrently IL-2, IL-4
      production peaked with maximal granuloma growth and declined with the onset of
      the immune modulation of the inflammation. Whereas these latter lymphokines
      appear to play a proinflammatory role, IFN-gamma when administered in large doses
      diminished granulomatous inflammation, plays a regulatory role in the maintenance
      of the granulomatous response. The T helper cell population of the granulomas may
      also influence the lymphokine profile of the developing granuloma. So far
      precursor type TH0, and TH2 subset of helper cells have been cloned from liver
      granulomas. The former secreted both IL-2, IL-4 and IFN-gamma lymphokines and
      adoptively transferred the granulomatous response.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7713556
TI  - Macrophage activation and innate resistance to infection in SCID mice.
AB  - Resistance to infection against a variety of pathogens requires the co-ordinated
      interaction of both the innate and acquired immune responses. Mice bearing the
      SCID mutation are devoid of T and B cells but retain elements of the innate
      immune system including natural killer (NK) cells, macrophages, granulocytes and
      complement proteins. Using the SCID model we have identified a T cell independent
      mechanism of macrophage activation mediated by the secretion of IFN-gamma from NK
      cells. This process occurs in response to a variety of parasites and bacteria
      including Listeria monocytogenes, and is strictly regulated both in vitro and in
      vivo by cytokines such as IL-2 and IL-10. Here we discuss the mechanisms of NK
      cell activation and regulation and describe a new model of opportunistic
      infection in SCID mice with the AIDS related pathogen Cryptosporidium parvum.

PMID- 7713557
TI  - The mRNA-phenotype of granuloma formation: CD4+ T cell-associated cytokine gene
      expression during primary murine listeriosis.
AB  - In murine listeriosis, elimination of bacteria and immunity to reinfection
      critically depend on Thy1+ CD4- cells, while cell-mediated inflammatory phenomena
      such as DTH and granuloma formation are mostly mediated by CD4+ T cells. In an
      attempt to correlate T cell phenotype and function with a particular set of
      cytokines produced, we examined the cytokine gene expression profile associated
      with the presence or absence of Thy1+, CD4+ and/or CD8+ cells in the livers of
      mice during a primary infection with L. monocytogenes. The presence of CD4+ cells
      was found to be closely associated with mRNA expression for IL-2, IL-3 and IL-4,
      a 5-fold increase in expression of TNF-alpha and GM-CSF and a 25-fold increase in
      expression of IFN-gamma and TNF-beta mRNAs, and temporally coincided with the
      development of granulomatous lesions. In vivo neutralization of TNF-alpha and, to
      a lesser extent, IFN-gamma resulted in abrogation of granuloma formation. A
      similar correlation between the presence of CD8+ cells and mRNA expression for
      any one of the cytokines studied did not exist, pointing to a qualitatively
      different mechanism of CD8+ T cell mediated cure of listeriosis.

PMID- 7713560
TI  - Roles of cytotoxic delayed-type hypersensitivity and macrophage-activating cell
      mediated immunity in the pathogenesis of tuberculosis.
AB  - The tubercle bacillus is a facultative intracellular parasite that grows well in
      non-activated macrophages. When large numbers of these bacilli have grown
      intracellularly within such macrophages, a cytotoxic immune response, herein
      called tissue-damaging (or necrotizing) delayed-type hypersensitivity (DTH),
      kills the macrophages (and usually some of the surrounding tissue), forming the
      caseous center of the developing tubercle. In solid caseum, tubercle bacilli may
      survive, but do not multiply. When bacilli escape from the edge of the caseum,
      they are rapidly ingested by nearby viable macrophages. If these macrophages have
      not been activated, the bacilli again multiply intracellularly, and the cytotoxic
      immune response kills the bacilli-laden macrophages (and surrounding tissue),
      thus enlarging the caseous center. In hosts that develop poor activation of
      macrophages, this process is repeated until much of the lung is destroyed. In
      hosts that can develop good activation of macrophages (by cytokines from antigen
      specific T cells), herein called cell-mediated immunity (CMI), the caseous
      centers become surrounded by these activated macrophages, which ingest and
      destroy the bacilli escaping from the caseum. This process can arrest the
      disease. Unfortunately, the caseous center may liquefy in such resistant hosts.
      In the liquefied menstruum, the bacilli may grow extracellularly (for the first
      time during the course of the disease), reaching tremendous numbers. The
      cytotoxic immune response to these numerous bacilli and their tuberculin-like
      products causes much tissue necrosis, including erosion of the walls of small
      bronchi, which results in cavity formation. From such cavities, the bacilli
      spread to other parts of the lung and to the environment. The extracellular
      multiplication of tubercle bacilli in the liquefied caseum is the main reason why
      tuberculosis perpetuates itself in mankind. It is also the reason why
      antimicrobial drug-resistant bacillary strains develop. To elucidate the various
      mechanisms involved in macrophage activation, caseation, and liquefaction is a
      major challenge for tuberculosis researchers today.

PMID- 7713562
TI  - T cell helper types and endocrines in the regulation of tissue-damaging
      mechanisms in tuberculosis.
AB  - The necrotising immunopathology, which is accompanied by very little
      mycobactericidal activity, is probably the key to the pathogenesis of
      tuberculosis. Conventional chemotherapy fails to correct this immunoregulatory
      anomaly, so the host response does little to assist the drugs in the removal of
      the "persister" subpopulation of bacteria. Therefore chemotherapy must be
      prolonged for at least 6 months, with consequent problems of cost, resistance,
      and compliance. If we can learn to switch off the necrotising pathway, and
      replace it with bactericidal mechanisms, treatment of the disease will be
      enormously improved and shortened. One problem is that we do not know the
      mechanism of cell-mediated immunity to tuberculosis in man. On the other hand, we
      are gaining some insights into the mechanism of the necrosis, and there are
      encouraging indications that it can indeed be separated from immunity, and that
      it can be suppressed by suitable immunotherapy. We present here some evidence
      that when a TH2 response is superimposed upon a pre-existing TH1 response, the
      resulting cell-mediated inflammatory site becomes exquisitely sensitive to
      cytokine-mediated damage. There is clear evidence for a TH2 component in the
      immune response of tuberculosis patients. This inappropriate TH1 to TH2 shift may
      result from subtle endocrinological changes brought about by M. tuberculosis and
      the response to it. Immunotherapy should aim to switch off this TH2 component.

PMID- 7713561
TI  - Adhesion molecules mediating recruitment of monocytes to inflamed tissue.
AB  - Three families of cell-surface proteins are largely responsible for the adherence
      of leukocytes to cells and matrices: integrins, immunoglobulin (Ig)-related
      molecules and selectins. Blood monocytes express beta 1 integrins VLA-4, -5 and 
      6 and beta 2 integrins CD11a/CD18, CD11b/CD18 and CD11c/CD18. These cells also
      express the Ig-related molecules ICAM-1, -2 and -3, ligands for the beta 2
      integrins. In addition, monocytes express L-selectin and the oligosaccharides Lex
      and sialyl Lex, ligands for the endothelial selectins E- and P-. In vitro studies
      with blocking antibodies have identified adhesion molecules participating in the
      adherence of monocytes to one another, to T lymphocytes and to vascular
      endothelial cells. These antibodies also block adhesion-dependent monocyte
      activities, such as cytotoxicity of tumor cells, antigen presentation,
      phagocytosis of large particles, induction of cytokine secretion, formation of
      multinucleated giant cells and HIV-induced syncytium formation. In vivo studies
      in animals have demonstrated participation of L-selectin and CD11b/CD18 in
      monocyte accumulation in inflamed peritoneum. Moreover, treatment with anti-CD11b
      antibodies potentiates primary listeriosis and inhibits the macrophage
      recruitment and granuloma formation, and anti-CD18 antibodies block ear swelling
      in Mycobacterium tuberculosis-immunized animals following challenge with PPD.
      Adhesion molecules may also play key roles in the pathogenesis of tuberculosis
      and AIDS.

PMID- 7713564
TI  - Protective and memory immunity in mice infected with Mycobacterium tuberculosis.

PMID- 7713563
TI  - Macrophage nitric oxide mediates immunosuppression in infectious inflammation.
AB  - A vaccine strain of live, attenuated Salmonella typhimurium induces profound
      immunosuppression in inoculated mice 7 days after injection. Immunosuppression to
      mitogens and inability to mount plaque-forming responses to sheep red blood cells
      occurs in spite of many parameters of upregulated macrophage function and
      protection against challenge with virulent Salmonella. Studies show that
      macrophage nitric oxide mediates the immunosuppression and presumably also the
      early-onset protective capacity of the vaccine. A model of "bystander lymphocyte
      autotoxicity" is presented to explain the mechanism of immunosuppression. The
      model proposes that Salmonella-activated macrophages generate nitric oxide which
      inactivates lymphocytes in the vicinity, so they become dysfunctional. Inhibition
      of nitric oxide by NG-monomethyl-L-arginine reverses immunosuppression. Evidence
      is presented that supports a relationship between the microbial burden in the
      spleen, the degree of nitric oxide produced, and the extent of immunosuppression.
      It is proposed that this model of microbial immunosuppression mediated by nitric
      oxide is generalizable for understanding immunosuppression and loss of delayed
      type hypersensitivity induced by other microbes, such as Mycobacteria and measles
      virus. The model could account for anergy during mycobacterial infections,
      particularly when the burden of acid-fast bacilli is high, as well as loss of
      skin test reactivity to tuberculin during measles infection.

PMID- 7713565
TI  - Role of T cell subsets in immunity against intracellular bacteria: experimental
      infections of knock-out mice with Listeria monocytogenes and Mycobacterium bovis
      BCG.
AB  - The generation of knock-out mice with targeted gene deletions has already proven
      its enormous value for our understanding of the antimicrobial immune response.
      Here, we describe studies with knock-out mice deficient in the TCR-beta gene,
      lacking alpha/beta T cells; in the TCR-delta gene, lacking gamma/delta T cells;
      in the beta 2m gene, lacking beta 2-microglobulin, and hence cell surface
      expressed MHC class I and functional CD8 T cells; and in the H-2I-A beta gene,
      lacking cell surface expressed MHC class II and hence functional CD4 T cells.
      These mice were infected with Listeria monocytogenes or Mycobacterium bovis BCG
      as representative microbes which primarily activate CD8 T cells or CD4 T cells,
      respectively. Data described in this treatise demonstrate that the different gene
      deletions had an impact of varying degree on antibacterial defense and on the
      formation of granulomatous lesions. At the same time, the data point to a
      compensatory potential of the incomplete immune system. We assume that deletions
      in the major immune effector cells promote the emergence of a second line of
      defenders which frequently remain silent in the normal immune system. Thus, our
      data illustrate an enormous redundancy of the immune system, which, however, is
      not abundant since it takes over essential functions in the immunodeficient
      situation.

PMID- 7713566
TI  - Protective role of interferon gamma, tumor necrosis factor alpha and interleukin
      6 in Mycobacterium tuberculosis and M. avium infections.
AB  - The screening of the cytokines that are involved in the control of mycobacterial
      infections in vivo may be used to select candidates for immunotherapeutical
      trials. We looked at the in vivo expression of different cytokines during
      Mycobacterium avium infection of mice and found a correlation between resistance
      and the level of expression of IFN-gamma and TNF-alpha. The use of specific
      neutralizing antibodies in vivo led to the identification of IFN-gamma and TNF
      alpha as protective cytokines acting at the effector level of resistance to M.
      avium and M. tuberculosis. Furthermore, we found that IL-6 was involved in the
      induction of protective T cells in M. avium infections and that it was necessary
      to maintain sterilizing immunity in mice infected with M. tuberculosis. Regarding
      the antimycobacterial mechanisms of the macrophage against M. avium we found no
      role for oxygen or nitrogen reactive intermediates but rather the involvement of
      phagosomal acidification.

PMID- 7713567
TI  - Experimental approaches to mechanisms of protection and pathogenesis in M.
      tuberculosis infection.
AB  - It has, for many years, been widely assumed that the fundamental mechanism of
      protection in tuberculosis infection is a CD4 T cell response producing
      lymphokines that activate macrophages to kill or restrict the intracellular
      growth of M. tuberculosis. Just as certain cytokines, e.g. IFN-gamma, are
      currently perceived to be important for protection, others, particularly tumor
      necrosis factor (TNF), are thought to be responsible for much of the tissue
      destruction associated with the disease. Yet there are remarkably few critical
      experimental or clinical data that have defined the immunological requirements
      for protection and pathogenesis. One of the initial stimuli to the work we have
      undertaken has been careful reflection on the results of the many prospective
      trials of BCG against tuberculosis. Two aspects have impelled us to reconsider
      conventional wisdom. The first, of course, is the wide discrepancy in the degree
      of protection imparted, ranging from 0% in South India to 77% in the British MRC
      trial (1, 2). The second is that, in all trials that examined them, skin test
      conversions to tuberculin positivity were 85% or greater, indicating a disparity
      between the presence of delayed hypersensitivity to tuberculin and protection. We
      and others have argued (1, 2) that there are multiple possible explanations for
      this discrepancy, the principal one being protection caused by infection with
      environmental mycobacteria. But, the general point raised is whether cell
      mediated immunity as manifested by CD4+ cell production of lymphokines and
      macrophage activation is a sufficient mechanism for protection against M.
      tuberculosis infection.

PMID- 7713568
TI  - The T cell response to secreted antigens of Mycobacterium tuberculosis.
AB  - Recent information from several laboratories points to proteins secreted from
      live Mycobacterium tuberculosis as being involved in protective immunity. We have
      studied protein release from M. tuberculosis during growth and have defined 3
      different groups of proteins: excreted proteins, secreted proteins of the outer
      cell wall and cytoplasmic proteins released at late culture timepoints. These
      findings have lead to the definition of a short-term culture filtrate (ST-CF)
      enriched in excreted/secreted proteins and with a minimal content of autolytic
      products. ST-CF was tested as antigen in experimental vaccines against
      tuberculosis. A vaccine based on the adjuvant dimethyldioctadecylammonium
      chloride (DDA) was constructed and demonstrated to induce a potent cell mediated
      immune response of the Th-1 type. The vaccine was tested in parallel with a BCG
      standard vaccine and both vaccines induced a highly significant protection of the
      same magnitude. Molecules within the Ag85 complex and a 6-kDA secreted protein
      were mapped as the major antigenic targets for long-lived T cells involved in
      protective immunity against M. tuberculosis.

PMID- 7713569
TI  - Prospects for low dose BCG vaccination against tuberculosis.
AB  - Efficacious vaccination against fast growing pathogens results in a rapid,
      secondary immune response on natural infection; this provides protection to the
      vaccinated individual in the race between developing effective immunity and the
      rapid multiplication of the pathogen. In certain chronic diseases, due to slow
      growing pathogens, cell-mediated immunity alone can contain the infection, and
      yet an antibody response is sometimes induced, at the expense of the cell
      mediated response, upon natural infection. Such situations arise in leprosy and
      the leishmaniases and most probably in tuberculosis. AIDS and syphilis. In these
      cases, the purpose of vaccination must be to ensure that a stable, protective,
      cell-mediated immune response is inevitably induced upon natural infection. We
      believe we have developed a general strategy for causing a pathogen-specific
      imprint upon the immune system so that a stable, protective, cell-mediated
      response is inevitably induced in all individuals upon natural infection. BALB/c
      mice are "susceptible" to Leishmania major in the sense that they mount a non
      protective antibody response on substantial infection, and consequently suffer
      chronic and progressive disease. We have demonstrated that infection with low
      doses of parasites induces only cellular immunity, and establishes the desired
      imprint. Mice exposed to low doses and challenged some months later with a
      substantial, normally pathogenic dose of parasites, mount a stable, protective,
      cell-mediated response and the vaccinated "susceptible" mice withstand the
      infection. We have recently managed to achieve a similar lock of the immune
      response of BALB/c mice to BCG into a cell-mediated mode by low-dose
      exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713570
TI  - Immunotherapy of tuberculosis with Mycobacterium vaccae NCTC 11659.
AB  - The history of immunotherapy for tuberculosis is briefly reviewed, and the early
      appreciation of the importance of secreted antigens, common mycobacterial
      antigens and stress proteins is noted. The methods by which Mycobacterium vaccae
      strain NCTC 11659 was selected for special attention, and results of some of the
      pilot studies of its use as an immunotherapeutic for tuberculosis are reviewed.
      The results suggested that immunotherapy with M. vaccae may be an important step
      forward in the treatment and eventual control of tuberculosis. Used in
      combination with modern short course chemotherapy, treatment failures and deaths
      during treatment can be significantly reduced. Preliminary data suggests that
      shortened courses of chemotherapy may be possible when combined with
      immunotherapy, and such treatment may also be effective in patients co-infected
      with HIV. Studies at several centers show that M. vaccae may have an important
      part to play in the treatment of multi-drug resistant tuberculosis, especially
      when resistance is of the primary type. The mechanism by which M. vaccae achieves
      these results may be through adrenal endocrine influences on immunity, but
      remains speculative.

PMID- 7713571
TI  - Cytokine regulation of disease progression in leprosy and tuberculosis.
AB  - Studies in our laboratory have focussed on the role of cytokines in the
      regulation of the cellular immune response and disease progression in two
      important mycobacterial infection of man, namely leprosy and tuberculosis. Our
      studies in leprosy have involved the use of key regulatory cytokines such as IFN
      gamma in the modulation of the cellular response of infected patients. We have
      investigated the effect of intradermal administration of low dose IFN-gamma on
      the lesions of anergic lepromatous patients and have reported an accelerated
      bacillary clearance from the skin. This was associated with the local
      accumulation of mononuclear cells and killing of infected macrophages. However,
      IFN-gamma administration also resulted in the induction of erythema nodosum
      leprosum, a toxic syndrome associated with excess TNF-alpha production. Both the
      toxic symptoms and the high levels of TNF-alpha production could be inhibited by
      thalidomide treatment, a drug we have shown reduces the half life of TNF-alpha
      mRNA. In preliminary clinical trials in tuberculosis patients we have attempted
      to use thalidomide to reduce TNF-alpha production and toxicities. These results
      are discussed.

PMID- 7713572
TI  - Experimental drugs and combination therapy.
AB  - The worldwide increase in tuberculosis, the additional problem of increasing
      multiple drug resistance (MDR) and the primary resistance of Mycobacterium avium
      requires new strategies in drug development and in therapy. The reason for
      development of MDR is manifold. One important factor is the change in cell wall
      construction which limits the penetration of the drug to the target receptor.
      This is supported by the observation that within a class of tuberculostatic drugs
      (identical mode of action) the more lipophilic derivative is more effective. In
      addition, it has been shown that mycobacteria within macrophages are able to
      synthesize additional multilamellar cell wall components. Several possibilities
      exist to overcome MDR. Besides improving the permeation properties of drugs, the
      development of synergistic drug combinations based on their special mode of
      action is a promising approach. This is illustrated with the highly synergistic
      combination of newly developed hydrazones and thiacetazone respectively with
      rifampicin. Chance combinations which may even lead to antagonism have to be
      avoided. Examples of antagonistic behavior of the combinations clofazimine
      dapsone and ofloxacin-rifampicin are discussed. An optimization procedure has
      been developed based on the determination of the specific resistance of patient
      derived mycobacteria against single drugs and their combinations. With its use,
      an individual optimal treatment becomes feasible. Preliminary clinical experience
      is encouraging.

PMID- 7713573
TI  - Use of liposome preparation to treat mycobacterial infections.
AB  - Infections caused by organisms of the genus mycobacteria, such as tuberculosis M.
      avium disseminated infection in AIDS patients and leprosy, are extremely common
      around the world. Mycobacteria are intracellular organisms that invade and
      multiply chiefly within phagocytic cells. Antibiotic resistance among
      mycobacteria is a growing concern. M. tuberculosis resistant to INH and rifampin
      are increasing in major urban centers of the developed and in the developing
      world. M. avium is characteristically resistant to most anti-tuberculosis
      antibiotics. Furthermore, therapy of mycobacterial infections takes a long time
      and most of the drugs have potential side effects and toxicity. In addition,
      mycobacteria is found within cells and antimicrobials need to be able to achieve
      adequate concentration within the compartment where mycobacteria is located.
      Liposome preparations, containing antibiotics, have a theoretical advantage in
      being able to deliver high concentrations of antimicrobials into the infected
      cell. Studies done thus far, in vitro and in vivo, have confirmed this premise,
      when comparing drug entrapped in liposomes with free drug. This paper summarizes
      the results obtained using liposome preparations to treat mycobacterial
      infections.

PMID- 7713575
TI  - Transfusion immunology and medicine. Proceedings of the 12th International
      Convocation on Immunology. Buffalo, New York, May 14-18, 1994.

PMID- 7713574
TI  - Mechanisms of drug resistance in Mycobacterium tuberculosis.

PMID- 7713576
TI  - Transfusion-transmitted cytomegalovirus infection.

PMID- 7713578
TI  - Testing blood donors for HIV: current controversies.
AB  - Despite an estimated risk of HIV infection from anti-HIV screened blood
      transfusions of less than one in 225,000 per unit, there continues to be strong
      pressure to implement additional donor screening and viral inactivation
      procedures. Decisions to implement such procedures must be based on analyses that
      incorporate accurate estimates of residual risk, and data-based projections for
      the reduction in risk that would result from each measure. Since the residual
      risk of HIV is primarily due to donations given in the infectious pre
      seroconversion window, effort must be directed at: reducing donations by persons
      in this window; employing tests that narrow the window; and development and
      implementation of procedures that inactivate viral compartments that predominate
      during the window. Unfortunately, as the risk of HIV has declined to near
      undetectable levels, the challenge of generating appropriate data to evaluate new
      measures, and thereby support rational policy decisions, has increased inversely.
      To meet this challenge, we must refine our understanding of the virological
      characteristics of early HIV seroconversion, and of the types of donors who
      present in the seroconversion window. Thoughtful application of a thorough
      understanding of the seroconversion window, in the context of accurate HIV
      incidence data in the donor settings, should enable us to assure the public of a
      safe blood supply while resisting inappropriate implementation of unnecessary and
      usually non-specific procedures.

PMID- 7713577
TI  - Existing problems in the testing for infectious diseases.
AB  - Current methods for testing donated blood for presence of infectious viral agents
      in the USA differ from those used in other countries because of the USA Food and
      Drug Administration's (FDA) control which inhibits rapid introduction of testing
      methods or improvements. Delays in FDA approval may occur because of concerns
      about methodology or the state of knowledge about the disease it is intended to
      detect as well as due to variability between manufacturers. Despite strict FDA
      control, testing problems continue to occur in the USA. No approved method
      detects infectious agents during the "window period," and variations in
      detection, i.e., false positives and false negatives (even with confirmatory
      testing), continue to occur. The effect of physical and chemical changes (e.g.,
      various anticoagulants) on samples has not been thoroughly evaluated. Test
      performance problems include lapses in sample identification, failure to use
      routine laboratory controls, improper calculation and reporting of results,
      improper acceptance of test runs and failure to properly detect and retest
      samples when carryover from very reactive samples occurs. For these reasons,
      transfusion-related disease transmission continues to occur. The current USA
      emphasis on good manufacturing practices should provide continuous improvements.

PMID- 7713579
TI  - Hepatitis testing.
AB  - There has been remarkable progress in hepatitis testing in recent years. This
      article reviews the transmission of Hepatitis A by blood products indicating that
      it is a rare event. However, it has been recently observed with certain
      preparations of Factor VIII concentrate. Hepatitis B transmission has been
      effectively reduced by the application of HBsAg screening tests, and screening
      for antibodies to HBcAb. Hepatitis C transmission has been substantially reduced
      by the used of the second generation tests for antibodies to HCV. A new
      generation of screening tests for HCV is expected to be licensed for use in the
      United States in the near future, and should further reduce the risk of
      transmission of HCV. At the present time, the incidence of post-transfusion
      hepatitis in hospitalized patients is indistinguishable from the incidence of
      hepatitis among patients who did not receive blood transfusion.

PMID- 7713580
TI  - Bacterial contamination of blood products and the value of pre-transfusion
      testing.
AB  - There has been a dramatic increase recently in the number of reports of septic
      episodes associated with both red cell and platelet concentrate transfusions.
      These reports suggest that transfusion-associated septic reactions may occur as
      often as 1 per 4000 platelet transfusions, however, the true incidence of the
      bacterial contamination of stored cellular blood components has not yet been
      established. Recently developed automated techniques for the detection of
      bacteria are much more rapid than direct plating techniques. Such rapid
      techniques can be used to monitor the sterility of cellular blood products with
      greater sensitivity than Gram staining; using a small aliquot of the blood
      product taken soon after collection. Using such equipment, the incidence of
      bacterial contamination of 15,838 random donor platelet concentrates collected
      over a six-month period was determined and evidence of bacterial contamination
      was found in 32. Seven were classified as confirmed, 10 as unconfirmed and 12 as
      non-confirmed positives. The confirmed positivity rate was thus 4.4 per 10,000.
      This rate represents the minimum incidence of bacterial contamination of platelet
      concentrates and the true rate is likely higher, as some of the unconfirmed
      positives are likely to have been found to be positives, had the original
      platelet concentrate been available for culture. The true positive rate is
      therefore estimated to be between 4.4 and 10.7 per 10,000. Given this rate of
      bacterial contamination, it is our contention that all platelet concentrate units
      be monitored for bacteriologic sterility prior to their issue.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7713581
TI  - What is important on the red blood cell surface.
AB  - Blood group antigens have provided tools for investigation of the red cell
      surface and been very useful as genetic markers in family, population and
      forensic studies. Precise definition of phenotypes is very important. Application
      of MAIEA (monoclonal antibody-specific immobilisation of erythrocyte antigen), a
      recently reported technique, to identify antigens and to assign red cell antigens
      to a particular membrane component is described: location of Knops system
      antigens on CR1 is confirmed and provisional assignment of Cromer system antigens
      to the different short consensus regions of decay accelerating factor (DAF) is
      described. Variability of red cell antigen expression is considered. The
      possibility is discussed that factors other than alterations in Rh genes may be
      responsible for some Rh variant phenotypes. Some C variants, two of which are
      associated with low incidence antigens, are described. The relationship of Xga
      with the quantitative polymorphism of 12E7 antigen is reconsidered in light of
      some recent immunochemical studies.

PMID- 7713582
TI  - Functional factors in the red cell membrane: interactions between the membrane
      and its underlying skeleton.
AB  - Recent studies involving two abnormal red cell phenotypes (South-east Asian
      ovalocytosis and Leach phenotype) provide novel information concerning the nature
      and significance of interactions of both the anion transport protein AE-1 (syn.
      band 3) and Glycophorins C and D with the underlying skeleton. The location of
      Wra and Dia blood group antigens to mutations on AE-1 at residues 658 and 854
      respectively, together with the availability of monoclonal antibodies recognising
      epitopes dependent upon the integrity of the third extracellular loop of AE-1,
      have allowed us to study the organisation of the membrane domain of the mutant AE
      1 found in South-east Asian ovalocytes (AE-1 SAO). The results suggest that the
      organisation of the whole membrane domain of AE-1 SAO is abnormal and that the
      organisation of other integral membrane proteins like those involved in
      expression of Rh blood group antigens may also be affected. Increased homo- and
      hetero-associations involving AE-1 SAO and other integral proteins may in turn
      result in reduced membrane flexibility. Purified protein 4.1 binds with 50-fold
      higher affinity to protein 4.1 depleted normal red cell membranes than to protein
      4.1 depleted red cell membranes of Leach phenotype which lack Glycophorin C (GPC)
      and Glycophorin D (GPD). Experiments using purified protein 4.1 and p55 together
      with synthetic peptides corresponding to different regions of the cytoplasmic
      domain of Glycophorins C and D (GPC/D) demonstrate that protein 4.1 interacts
      directly with GPC through residues 82-98. They also show that p55 binds to GPC
      through residues 112-128. Since p55 also binds directly to protein 4.1 it is
      clear that protein 4.1 can bind to GPC through two different sites either
      directly through residues 82-98 or indirectly through p55. These results show
      that GPC and GPD provide major attachment sites for the red cell skeleton via
      protein 4.1 and that p55 is part of this complex.

PMID- 7713583
TI  - Hot spots in the red cell membrane: molecular aspects of some red cell antigens.
AB  - After decades of studying the human blood groups by serological and, more
      recently, biochemical techniques, analysis of blood group genes at the molecular
      level has confirmed that a variety of different genetical events have given rise
      to the vast complexity of blood group systems. In order to illustrate this 4
      blood group systems have been selected: ABO and H, involving carbohydrate
      determinants, and MNS and Rh, involving predominantly protein antigens. The
      molecular basis of the A1, A2, B, and O groups, and of the rare H-deficiency
      phenotypes will be described. The Sta antigen of the MNS system will be discussed
      in order to illustrate the variety of different genetic mechanisms that can give
      rise to a single rare antigen. Finally, recent work on the molecular basis of the
      polymorphic Rh antigens, D, C, c, E, and e, and on some rare Rh phenotypes,
      Rhnull, D--, and r's, will be explained briefly in order to emphasize the
      complexity of blood group genetics.

PMID- 7713584
TI  - Blood group antigens as tumor markers, parasitic/bacterial/viral receptors, and
      their association with immunologically important proteins.
AB  - Blood group antigens (BGAs) are chemical moieties on the red blood cell (RBC)
      membrane. Some BGAs (e.g., A, B, H, Lewis, P, I) are widely distributed
      throughout the body and may not be primarily erythroid antigens. Statistical
      correlations with ABO blood groups and disease have been made for years and have
      been highly controversial. It is not known if BGAs have a biological function.
      There are increasing reports of BGAs [e.g., Le(x) (an isomer of Le(a)), Le(y) (an
      isomer of Le(b)), T, Tn, "A-like"] appearing as "new" antigens on malignant
      tissue. Their presence and membrane density appears to correlate with the
      metastatic potential of the tumor. This often parallels loss of normal BGAs
      (e.g., ABH) from the tissue. Some of these antigens have been shown to influence
      the humoral and cellular response and have been used in assays to determine
      preclinical cancer, and in tumor immunotherapy. Interactions of some parasites
      and bacteria with human cells have been shown to depend on the presence of
      certain BGAs. P. vivax malarial parasites only enter human RBCs when the Fy6
      Duffy blood group protein is present on the RBCs. Certain E. coli will only
      attach to the epithelial cells of the urinary tract if P or Dr BGAs are present
      in the epithelial cells. The P antigen is also the RBC receptor for Parvovirus
      B19. Leb has recently been found to be the receptor for H. pylori in the gastric
      tissue. The high frequency BGA, AnWj, is the RBC receptor for H. influenzae. BGAs
      have been shown to be associated closely with some important complement proteins.
      Ch/Rg BGAs have been found not to be true BGAs but are RBC-bound C4 (C4d).
      Knops/McCoy/York BGAs have been located on the C3b/C4b receptor (CR1). The high
      frequency BGAs of the Cromer (Cr) system are located on decay accelerating factor
      (DAF or CD55). Cartwright (Yt) BGAs are located on RBC acetylcholinesterase
      molecules. DAF and acetylcholinesterase are on phosphatidylinositol-glycan (PIG)
      linked proteins. When the PIG anchor is missing from RBCs, as in paroxysmal
      nocturnal hemoglobinuria, the affected RBCs lack all Cr, Yt, JMH, Hy/Gy, Do and
      Emm BGAs. The most important ligand for P, E and L selectins is sialyl-Le(x).
      This interaction is the tethering stage that start the leukocytes' journey from
      the circulation into the tissue. It appears that malignant cells may move through
      tissue in a similar way and may explain the close association of Le(x) with
      metastasis. Thus, there are increasing data suggesting a biological role for BGAs
      unrelated to the RBC.

PMID- 7713585
TI  - The role of the lymphocyte in an immune response.
AB  - The immune system has evolved in the human being as an elaborate mechanism to
      distinguish itself from all else that is not self. This process serves in the
      defence against invaders. The cells of the immune system learn to tolerate all
      tissues, cells and proteins of the body. Failure to control the state of
      tolerance results in autoimmunity. The understanding of the role of T-cell
      receptors (TCR), the Major Histocompatibility Complex (MHC), adhesion molecules
      and growth factors in antigen recognition has lead to the exploration of various
      means to modulate the immune response. Safety measures exist to prevent the
      immune system from attacking its host. The antigen has to be recognized by the T
      cell. This involves the TCR and the MHC. In addition it must receive a second
      signal to become activated. The second signal involves a protein such as B7
      binding with CD28. Certain specialized cells, macrophages, dendritic cells and
      activated B-cells can deliver this second signal for activation; receipt of only
      one signal can prevent activation. The elucidation of the role of cell-to-cell
      interactions, the adhesion molecules involved and the accessory growth factors
      provides modalities for selectively modifying the immune response. This would be
      of great relevance in autoimmunity and transplantation.

PMID- 7713586
TI  - Neutrophil antigens, from bench to bedside.

PMID- 7713587
TI  - Viral contamination of blood components and approaches for reduction of
      infectivity.
AB  - Currently, the United States blood supply offers a relatively low risk of viral
      infection. This is a result of careful selection of donors and extensive
      laboratory testing using sensitive procedures. Epidemiologic data show that there
      is some room for improvement in donor selection, but such improvements cannot be
      expected to entirely eliminate the collection of blood from infectious donors.
      Similarly, increased numbers of tests, along with improvements in the analytic
      sensitivity of these tests, may further reduce risk, but again, complete safety
      cannot be assured. Consequently, there is continuing interest in the development
      of safe and effective procedures for viral inactivation of single donor blood
      components. In order to establish appropriate expectations for such inactivation
      procedures, it is necessary to understand the titers and distributions of viral
      contaminants in blood components. Viruses may variously occur free in the plasma,
      as replicative forms in actively infected leukocytes, as integrated proviral DNA
      and perhaps, nonspecifically associated with cellular surfaces.

PMID- 7713588
TI  - Immunologic effects of blood transfusion.
AB  - Blood transfusion is associated with numerous clinical phenomena attributable to
      immune suppression. Homologous blood transfusion is associated with declines in
      lymphocyte numbers and inhibition of lymphocyte function. In dialysis patients
      this immune suppression is accompanied by prolongation of survival of
      subsequently transplanted allografts. For patients undergoing surgical
      procedures, the receipt of homologous blood increases the risk of postoperative
      infectious complications. Patients with malignancies have significantly increased
      recurrence and mortality rates when removal of their tumor is accompanied by the
      administration of blood. The clinical course of Crohn's disease may be
      beneficially influenced by transfusion at the time of resection of diseased
      bowel. Women suffering recurrent abortion may carry to term following transfusion
      of spouse leukocytes. Experimental studies, in addition to replicating the
      clinical studies, have documented that transfusion inhibits wound healing. Blood
      transfusion, the oldest form of transplantation, causes profound and prolonged
      alterations in immune function which result in clinical phenomena which can be
      either beneficial or detrimental to the recipient.

PMID- 7713589
TI  - Transfusion reactions: the changing priorities.
AB  - Over the last dozen years the relative frequencies of specific transfusion
      reactions have markedly altered, in general for the better. Although AIDS remains
      the Public's primary concern, the risk of AIDS from a transfusion is extremely
      low at this point. Hepatitis remains the most common infectious complication of
      blood transfusion, but only 1 in 6,000 units now carry a risk, whereas in the
      early 1980's the risk is believed to have been close to 10% per patient.
      Transmission of HTLV-I/II has also been markedly reduced by tests of donor sera.
      In contrast, cytomegalovirus has become of increased importance in view of the
      large number of patients immunosuppressed for transplantation and cancer therapy;
      bacterial growth in blood components appears to be increasingly common; and
      Chagas disease is likely to become a serious transfusion problem in this country.
      More widespread use of filters which remove three logs or more of white blood
      cells from components should play a major role in reducing transfusion reactions
      further.

PMID- 7713590
TI  - The Ernest Witebsky memorial lecture. Red but not dead: not a hapless sac of
      hemoglobin.
AB  - The purpose of this presentation was to demonstrate that the red blood cell is
      not a hapless sac of hemoglobin and that much research is still needed for better
      understanding of its complexities. After a brief historical introduction the
      following subjects are presented: 1). Phosphofructokinase is the rate limiting
      step in the anaerobic glycolytic pathway. Ribose-5-phosphate, a metabolite of the
      oxidative pentose phosphate pathway is essential for the generation of
      phosphoribosylpyrophosphate which in turn is needed for the synthesis of
      adenosine monophosphate from adenine by the action of adenine phosphoribosyl
      transferase. 2). There are at least 17 blood group systems with more than 400
      epitopes expressed on the red cell membrane. The Rh null and the McLeod
      phenotypes associated with abnormally shaped red cells and hemolytic anemia are
      briefly described as is the present understanding of the nature of the Rh
      complex. 3). The structure of the cytoskeleton and the composition and behavior
      of the lipid bilayer are presented with some discussion of the MN and Ss
      sialoglycoproteins and the Leach phenotype. 4). Touched upon is the role of
      phosphoinositides with some emphasis on recent discoveries relating to the
      glycophosphoinositide protein anchor. 5). The intricacies of the many faceted
      transport mechanisms are introduced. Briefly mentioned are the mechanisms
      activated when regulatory volume adjustments occur in fine tuning red cell volume
      after exposure respectively to hypotonic or hypertonic stress. Sufficient
      evidence is presented to convince that a cell doesn't have to have a nucleus to
      be respected even though it is just a corpuscle.

PMID- 7713591
TI  - Blood transfusion, blood storage and immunomodulation.
AB  - Allogeneic blood transfusion is the most frequent allotransplantation procedure
      performed on a routine basis with no prior HLA-typing. Roughly 50% of the
      recipients of unprocessed red cells and platelets become alloimmunized. Evidence
      also exists for some degree of transfusion-induced immunosuppression. Prior
      transfusion has been shown to enhance kidney transplant survival and evidence of
      an increase in tumor recurrence and of infectious complications has also been
      presented. The presence of donor antigen-presenting cells appears to be a
      prerequisite for alloimmunization and they must be both viable and capable of
      presenting a costimulatory signal in order to induce IL-2 secretion and
      proliferation of responding CD4 T cells. APCs presenting antigen but no
      costimulatory signal can induce non-responsiveness in CD4 T cells, a possible
      mechanism of transfusion-induced immunosuppression. APCs in refrigerated blood
      continue to present antigen but progressively lose their ability to provide
      costimulation. By day 14 costimulatory capacity is absent and transfusion of such
      blood should not alloimmunize but could induce some degree of immunosuppression.
      Further refrigerated storage in excess of 2 to 3 weeks leads to induction of
      apoptosis in contaminating leukocytes. We have found that alloantigens-expressed
      on such cells do not appear to be recognized by responder T cells and transfusion
      of blood stored in excess of 3 weeks should neither alloimmunize nor
      immunosuppress.

PMID- 7713593
TI  - The role of cytokines in hemolytic transfusion reactions.
AB  - Experimental evidence is accumulating to support a central role for cytokines in
      the pathophysiology of hemolytic transfusion reactions. The production of tumor
      necrosis factor, interleukin-8, and monocyte chemoattractant protein occurs in
      whole blood in response to ABO incompatible red cells, a model of acute hemolytic
      transfusion reactions. Peripheral blood mononuclear cells may produce interleukin
      1 beta, tumor necrosis factor, interleukin-8, monocyte chemoattractant protein,
      and interleukin-1 receptor antagonist in response to IgG-coated red cells, a
      model of delayed hemolytic transfusion reactions. Cultured umbilical vein
      endothelial cells respond to conditioned plasma from ABO-incompatibility
      reactions by expressing the procoagulant tissue factor and the leukocyte adhesion
      molecules ELAM-1 and ICAM-1. These in vitro endothelial cell responses can be
      inhibited by neutralizing antibodies to tumor necrosis factor, suggesting that
      TNF may have a central role in intravascular coagulation and end-organ injury
      that may occur in acute hemolytic transfusion reactions.

PMID- 7713592
TI  - The tumor growth-promoting effect of allogeneic blood transfusions.
AB  - Over the past decade, many studies have suggested that allogeneic blood
      transfusions (ABT) may adversely affect a recipient. The ABT-associated
      deleterious effects include the development of transfusion reactions, graft
      versus-host disease, alloimmunization, and immunomodulation. While the ABT
      associated immunosuppressive effects might be beneficial for recipients of kidney
      allografts, in reducing the relapse rate in patients with Crohn's disease, and in
      ameliorating the rate of abortion in women with recurrent spontaneous abortions;
      evidence is accumulating that the immunosuppression associated to perioperative
      ABT might adversely affect overall prognosis in patients with a malignancy
      undergoing curative cancer surgery. In addition, the ABT-associated
      immunomodulation has been reported to be associated with an increased risk for
      postoperative bacterial infections. Data from both inbred and outbred
      experimental animal models indicate that ABT promote tumor growth. Evidence is
      available that this ABT-promoting tumor growth effect can be adoptively
      transferred to naive animals, using splenic immunocytes. Furthermore, data from
      the experimental animal models indicate that the ABT effect on the growth of
      tumors is due to the presence of the donor leukocytes in the transfused
      allogeneic blood, and that this deleterious effect can be ameliorated by the pre
      storage leukodepletion of the allogeneic blood. Importantly, recent evidence
      suggests that post-storage leukodepletion is inefficacious in preventing the ABT
      associated tumor growth promotion effect. While results from studies in
      experimental animals cannot necessarily be extrapolated to the clinical
      situation, these studies suggest that ABT promote tumor growth and that pre
      storage leukodepletion ameliorates this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713594
TI  - The role of cytokines and adhesive molecules in febrile non-hemolytic transfusion
      reactions.
AB  - Febrile non-hemolytic transfusion reactions occur not infrequently following
      transfusion. Our understanding of the molecular biology of these reactions has
      increased dramatically over the past few years. A variety of biological response
      modifiers have been shown to play a role in these reactions. These chemical
      messengers include cytokines, complement fragments, antibodies and adhesion
      molecules. Many of the clinical symptoms associated with these reactions are
      attributable to activation and generation of these substances. This review
      article will cover the role of cytokines in generation of non-hemolytic febrile
      transfusion reactions and the role of activation of adhesion molecules in the
      generation of TRALI (non-cardiogenic pulmonary edema). Our ability to modulate
      the generation of these chemical messengers could help us control clinical
      symptoms associated with these transfusion reactions.

PMID- 7713595
TI  - Neonatal anemia: pathophysiology and treatment.
AB  - All neonates experience a decline in circulating red blood cell (RBC) mass due to
      diminished erythropoietin (EPO) levels. This effect is more pronounced in small,
      premature infants and can lead to severe anemia and need for RBC transfusions-
      particularly, if repeated phlebotomy is required to monitor acutely-ill neonates.
      Although optimal RBC transfusion therapy has been a long-term challenge for
      neonatologists, the emergence of recombinant EPO as promising therapy for
      neonatal anemia is the major issue for 1994. Accordingly, this report for the
      12th International Convocation on Immunology (Transfusion Immunology and
      Medicine) will focus on this aspect of neonatal transfusion medicine. Although
      several controlled trials to evaluate EPO as therapy have been completed,
      definitive answers to all questions regarding efficacy and possible toxicity have
      not been provided. However, therapy with EPO plus iron and adequate nutrition is
      likely to be proven effective for the relatively late anemia of stable
      prematures. To date, EPO has not been shown, convincingly, to alleviate the
      anemia present early in the life of acutely-ill, premature infants.

PMID- 7713596
TI  - Quality of platelet concentrates.
AB  - Despite the current emphasis in transfusion medicine on regulatory compliance and
      cost containment, there is continuing activity in quality improvement of blood
      products. Quality can be assessed by measuring both benefit and risk. High
      quality products are those in which the benefit is maximized and the risk
      minimized. Risk, in the context of platelet transfusions, is minimized by
      reducing infectious agents, sources of allergic reactions, and other factors
      likely to cause adverse reactions in recipients. Benefit can be better described
      as potency. Potency is the ability to produce a desired effect. For platelet
      concentrates, potency has both quantitative [platelet yield] and qualitative
      [platelet viability, survival, and function] components. There are many
      activities which may influence the potency of the final transfused platelet
      product and these are summarized in Figure 1. It is helpful to review each step
      in order to assess the potential impact on the potency of the final transfused
      product.

PMID- 7713598
TI  - Growth factors and cord blood stem and progenitor cells.
AB  - This article reviews recent information on the proliferation kinetics of
      hematopoietic progenitor cells in patients on clinical trial with growth factors,
      and the use of umbilical cord blood as a source of transplantable stem and
      progenitor cells.

PMID- 7713597
TI  - The quality of red blood cells.
AB  - The evolving practice of medicine has required a number of changes in red cell
      product manufacture to ensure that the final product is more specifically
      tailored to the needs of the individual patient. As a result of the increasing
      concern over the risks of transfusion pharmaceutical standards of manufacture are
      now applied to blood component preparation. Studies have been undertaken to
      define the optimum method of blood processing, and newer technologies are
      emerging to allow acquisition of a more consistent dose of red cells in a fashion
      which may minimize the lesion of collection. Use of high efficiency 3+ generation
      filter technologies reduces leukokine build up during storage and improves the
      quality and purity of the stored blood product. The combination of new
      plasticizers for packaging and improved red cell additive solutions should allow
      the blood center to supply a more functional red cell with longer storage shelf
      life. Overall these developments should result in the provision of a more
      consistent dose of fully functional red cells to the recipient who will be less
      exposed to the undesirable sequelae of transfusion than previously.

PMID- 7713599
TI  - The development and use of oxygen-carrying blood substitutes.
AB  - The major criteria by which any blood substitute product will be evaluated prior
      to commercial usefulness will include evaluations of its: oxygen transport
      characteristics purity and physical properties potential for and modality of
      toxicities efficacy in various clinical settings biologic half life metabolism
      immunogenicity Although a thorough review of these aspects are laborious, they
      are necessary prior to the performance of clinical trials. The promise and
      availability of a clinically useful oxygen-carrying blood substitute has been
      long in coming, however we fortunately enjoy the continued supply of the safest
      blood products ever available. Further improvements in our homologous blood
      system continue, while we strive for the development of a blood substitute. The
      availability of a safe, multi-use oxygen-transporting product could significantly
      contribute and improve upon the care of acutely ill patients. Table I reviews the
      current status of the various categories of blood substitutes. We look forward to
      the introduction of one or more of these products in the near future.

PMID- 7713600
TI  - Novel cellular therapies.

PMID- 7713601
TI  - Transfusion strategies: opportunities for improvement.
AB  - Opportunities for improving transfusion practice that involve patient care,
      technological advancements, and technology changes in the clinical arena are
      discussed. Patient care should be enhanced by optimizing transfusion therapy and
      the source of donors of platelet concentrates, i.e., single donor platelets
      (obtained by plateletapheresis from a single donor) or to random donor platelets
      (containing a pool of six to eight platelet concentrates separated from whole
      blood donations). The availability of "third-generation" leukocyte-reduction
      filters provides the technology for significantly and consistently providing
      leukocyte-reduced blood components. The potential benefits of using these filters
      is presented. Platelet crossmatching represents a technology change involving
      clinical practice. Suggestions for incorporating this test into platelet
      transfusion algorithms are included.

PMID- 7713602
TI  - Transfusion-associated graft-versus-host disease and the irradiation of blood
      components.
AB  - Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but lethal
      disorder caused when viable donor lymphocytes engraft and proliferate in a
      susceptible transfusion recipient. Patients with immune deficiency disorders,
      hematologic malignancies and bone marrow transplants are at risk to TA-GVHD, as
      are premature newborns and transfusion recipients who are HLA heterozygous for an
      HLA-haplotype that is shared with an HLA homozygous donor. Irradiation of blood
      components with 2500 cGy will inactivate donor lymphocytes and prevent TA-GVHD.
      Platelets and granulocytes are not functionally impaired by this radiation dose,
      but red cells sustain detectable damage. Red cell units irradiated and stored for
      42 days have significantly higher supernatant recovery of chromium-51 labeled
      cells is sub-optimal. Based on these data, the maximum permissible storage time
      for irradiated red cells has been reduced to 28 days.

PMID- 7713603
TI  - Autologous blood transfusion: evaluation of an alternative strategy in reducing
      exposure to allogeneic blood transfusion.
AB  - The perceived risk of transfusion-transmitted disease led to the rejuvenation of
      autologous blood transfusion (ABT). ABT, a process in which the blood donor and
      recipient are the same, is increasingly becoming an integral component of the
      elective surgical protocol in many institutions. Various methods of ABT are being
      utilized. These include: preoperative blood donation, in which the patient
      donates blood prior to surgery and the blood is stored for an expected need
      during or after surgery; acute normovolemic hemodilution, in which blood is
      collected immediately prior to surgery and replaced with cell free fluids and
      then returned to the patient upon need; intraoperative blood salvage in which
      blood is collected from the surgical field and is reinfused after being washed
      and finally, postoperative blood salvage in which collected shed blood from
      surgical drains is reinfused to the patient. Although ABT is known to reduce the
      risk of allogeneic blood transfusion, it is not risk free and should be evaluated
      in relation to the patient's clinical picture. The combination of various methods
      of ABT in addition to the proper utilization of blood may consequently lead to
      the elimination of patients' exposure to allogeneic blood transfusion in many
      surgical procedures.

PMID- 7713604
TI  - Hematopoietic stem cells: "form--method--characteristics".

PMID- 7713606
TI  - Reducing the infectivity of blood components--what we have learned.
AB  - The safety of the nation's blood supply has improved over the last several years
      as a result of more intensive donor screening and viral testing. Concurrently,
      there has been more judicious use of blood components. Although the risk is
      small, transmission of blood borne viruses, bacteria and parasites can occur.
      Investigators have studied a myriad of processes for pathogen depletion and/or
      inactivation, including the use of chemicals, extended storage, filtration,
      heating, irradiation, photochemicals and washing. Pasteurization, methylene blue
      and solvent-detergent processes have been introduced in parts of Europe for
      improving the safety of plasma used for transfusion. The FDA is reviewing a
      license application for the solvent-detergent process. For red cells, use of
      highly efficient leukodepletion filters is believed to be equivalent to antibody
      testing for the prevention of CMV disease transmission. Otherwise, no successful
      treatments have yet been identified for red cells or platelets. Several
      photochemicals, which may be useful for treating these components, are being
      studied. However, there appear to be trade-offs between the extent of pathogen
      inactivation, platelet or red cell damage, and genotoxicity. These as well as
      other biological parameters and operational issues will need to be further
      evaluated before implementation can be considered.

PMID- 7713605
TI  - Uses of intravenous gammaglobulin in immune hematologic disease.
AB  - In summary, for intravenous gammaglobulin use of ITP in children and adults, it
      is clear that intravenous gammaglobulin is an effective way to increase the
      platelet count acutely and this will be faster than or as fast as any other
      therapy. However, there is no proven curative effect of IV gammaglobulin. Its use
      in situations requiring a rapid increase in the platelet count seems secure as
      does its use in children with chronic ITP. The latter however and the treatment
      of HIV-ITP may find IVIG treatment largely replaced in the future by IV Anti
      D(10) which is currently experimental. The use of a viral inactivated form of
      IVIG currently seems mandatory to avoid post-transmission hepatitis.

PMID- 7713608
TI  - Leukocyte filtration mechanisms. Factors influencing the removal of infectious
      agents from red cell concentrates.
AB  - The purpose of the present overview was to determine the factors influencing the
      removal of infectious agents from red cell concentrates by filtration. In
      general, the efficacy of the filtration method depends on the physical as well as
      the functional properties of blood cells. These properties are highly influenced
      by the changes exerted on the blood cells during blood collection, processing and
      storage and the filtration method itself. In particular, the removal of
      infectious agents of red cell concentrates by filtration will be determined by
      the type of virus and therewith the binding towards leukocytes, the type of
      bacteria and holding period before filtration, the deformability of infected
      cells and the disintegration of cells in the filter.

PMID- 7713607
TI  - Photodynamic virus inactivation of blood components.

PMID- 7713609
TI  - Use of leukodepletion filters for the removal of bacteria.
AB  - Recipient exposure to allogeneic donor leukocytes can mediate a number of
      immunologic complications of transfusion or can transmit leukotropic viruses
      carried by the donor. Leukocyte depletion of cellular blood components has been
      shown to reduce the incidence of such complications. In recent years, prestorage
      leukocyte depletion by filtration has also been suggested as a means of
      decreasing the incidence of bacterial overgrowth in cellular blood components.
      This review analyzes published studies on the use of leukodepletion filters for
      removal of Staphylococcus epidermidis and Yersinia enterocolitica from blood.
      Although ineffective for removal of S. epidermidis from Platelet Concentrates,
      inoculation studies demonstrate removal of low levels of Y. enterocolitica from
      Red Cell Concentrates. Based on these studies, four possible mechanism(s) for
      removal of bacteria by leukodepletion filters are analyzed: phagocytosis by
      leukocytes during a prefiltration holding period; complement-mediated bacterial
      killing enhanced by filtration; adherence of bacteria to leukocyte surfaces
      retained within the filter; and direct removal of bacteria by the filter media.
      Just as multiple mechanisms appear to account for the efficiency with which these
      filters deplete blood of leukocytes, it is likely that more than one mechanism
      accounts for the experimental observation that leukocyte depletion filters can
      reduce overgrowth of Y. enterocolitica in stored Red Cell Concentrates.

PMID- 7713611
TI  - Hospitals: from center to periphery.

PMID- 7713610
TI  - Explaining trends in health insurance coverage between 1988 and 1991.
AB  - This paper uses regression-based decompositions to examine the downward trend in
      insurance coverage between 1988 and 1991. I find that falling family incomes
      account for much of the decline in overall insurance coverage, while a secular
      decline in insurance coverage across all industries, firm sizes, employment
      statuses, income levels, and demographic groups accounts for most of the decline
      in employer-sponsored insurance among workers. Rising unemployment and changing
      patterns of industrial employment explain little of the decline in coverage
      across the entire population. Taken together, these results suggest that fewer
      employers are offering health coverage, workers are finding it difficult to pay
      their share of the premiums, and those without access to employer-sponsored plans
      are finding it harder to purchase nongroup insurance. Thus, it appears that the
      rising cost of health insurance coupled with falling incomes and profits during
      the recession account for the fall in health insurance coverage between 1988 and
      1991.

PMID- 7713612
TI  - Do shifts toward service industries, part-time work, and self-employment explain
      the rising uninsured rate?
AB  - It is conventional wisdom that the increase in the number of uninsured people
      during the 1980s was due, in part, to systematic trends in employment,
      specifically: 1) shifts from full-time to part-time jobs and to self-employment;
      and 2) changes in the industrial mix of employment, especially toward the service
      industries. This paper uses the March Current Population Survey data from 1980
      through 1987 to measure the contribution of these factors to the rise in the
      uninsured. In the first case, we find the premise of rising part-time work and
      self-employment to be untrue. In the second case, less than 15% of the decline in
      health insurance over this period was due to employment shifting from higher
      coverage to lower-coverage industries. Instead, the decline resulted from falling
      coverage rates across all industries. This is not to dismiss the possible
      importance of such employment trends over decades, but to emphasize the need to
      investigate other causes of the change during recent years.

PMID- 7713613
TI  - Risk selection in the health care market: a workshop overview.
AB  - In a voluntary health insurance market, risk selection poses serious and
      increasing problems. Responding to this concern, the Robert Wood Johnson
      Foundation sponsored an invitational meeting for public and private decision
      makers to understand the incentives for risk selection in the health insurance
      market and to discuss options for reducing risk selection practices. The meeting,
      held October 6, 1994, provided a framework for exploring this timely issue and
      served as a vehicle for understanding how health care reforms, such as insurance
      market regulation and risk adjustment mechanisms, both can reduce and exacerbate
      incentives for risk selection. This article sets the context for the three
      commissioned papers that follow; it summarizes the ideas presented and issues
      identified for future consideration. Failure to address risk selection will
      continue to have serious consequences both for access to care for vulnerable
      populations and for the financial viability of health plans.

PMID- 7713614
TI  - Potential methods to reduce risk selection and its effects.
AB  - Risk differences are inherent with voluntary enrollment or choice of health
      plans. If these desirable features are to be maintained, risk differences must be
      assessed and payments to plans adjusted. Perfect prediction of individual level
      costs is impossible, but it is feasible to approximate costs for large groups of
      employees joining a purchasing cooperative. When people within an employee group
      or cooperative can choose among different health plans, there is much more
      opportunity for risk selection. A fair but powerful referee to determine
      adjustment methods within the cooperative's zero-sum setting may reduce markedly
      the potential for selection problems.

PMID- 7713615
TI  - Too smart by half.

PMID- 7713616
TI  - The practice of risk adjustment.
AB  - This article focuses on risk adjustment under health care reform. It examines
      reasons for risk adjustment, how those reasons affect the method of adjustment,
      and practical issues that arise in the process of adjusting for risk. The paper
      concludes that adjusting payments to health plans makes the most sense. It
      advocates a risk adjustment agency that is regionally based and supportive of the
      public good. For risk adjustment to work, there must be a well-defined market and
      barriers to entry and exit.

PMID- 7713617
TI  - Making risk adjustment work for everyone.
AB  - This article explores how to reward health plans that serve people with
      disabilities and residents of low-income areas. We analyze health care
      expenditure patterns for Medicaid-covered persons with disabilities in Ohio,
      Missouri, Minnesota, and Wisconsin, demonstrating that diagnostic classifications
      are predictably related to resource utilization, and that health care
      expenditures are much more predictable for persons with disabilities than for the
      nondisabled. The implications of this analysis for risk-adjusted payment systems
      are explored. We also consider methods of assuring that health plans will provide
      high-quality care to the residents of inner city neighborhoods.

PMID- 7713618
TI  - Assessing relative health plan risk with the RAND-36 health survey.
AB  - Unbiased risk assessment models base health plan payments on enrollee health care
      needs. We explored the risk structure of employed adult health maintenance
      organization (HMO) members using the RAND-36 health survey. We used multivariate
      techniques to estimate risk weights on demographic and health status factors. The
      dependent variable was annual real total health plan expense for covered services
      for the year following the survey. Repeated random-split-sample validation
      techniques minimized outlier influences. Five scales improved prediction over
      simple demographic factors, but demographic factors still were required to
      achieve unbiased forecasts. Self-reported health status is a useful and powerful
      risk measure for adults.

PMID- 7713619
TI  - Reducing risk selection requires more than risk adjustments.

PMID- 7713620
TI  - Health risk and access to employer-provided health insurance.
AB  - The attractiveness of a job offering health benefits increases with a worker's
      expected medical expenditures. At the same time, employers have an incentive to
      screen out high-risk workers. Evidence from the 1984 Survey of Income and Program
      Participation indicates that employer screening dominates high-risk workers'
      desire to select jobs that offer insurance. Workers who describe their health as
      fair or poor, report difficulty with physical tasks, or have a work-related
      disability are less likely to receive employer-provided health insurance than
      healthy workers. Part of this effect is explained by the negative impact of poor
      health on earnings and labor supply.

PMID- 7713621
TI  - Economies of scope in physicians' work: the performance of multiple surgery.
AB  - While the fees for the large majority of physicians' services in the new Medicare
      Fee Schedule (MFS) are derived directly from studies of the resource costs
      involved, payments for one class of procedures, multiple surgery, are based
      instead on existing policies and conventions. Using surveys of physicians, we
      measured the work and time involved in performing 146 multiple surgeries. We
      found economies of scope exist in performing these services, particularly during
      the preoperative and postoperative periods. We also found some differences in
      economies across procedures. Based on our findings, we propose payment policies
      for multiple surgery.

PMID- 7713622
TI  - Imbecility, pauperism, and crime: an appraisal of their relationship to substance
      use, abuse, and dependence.
AB  - Freud had stated that human judgments of value "follow directly ... wishes for
      happiness--that, accordingly, they are an attempt to support ... illusions with
      arguments." This paper argues that substance use/abuse/dependency treatment has
      been a failure because we understand little about eradicating the significant
      concerns associated with the use of chemicals that haunt mankind: ignorance,
      poverty, and crime. While technologies advance at dizzying speed, the human
      capacity to integrate new information and to achieve a quality life seems to
      evade many. The author presents her treatment regime which has helped some
      patients. But the psychologist is only one contributor to psychotherapy,
      habilitation and rehabilitation. It is advisable that each member of the
      professional and lay communities "tend to their own garden."

PMID- 7713623
TI  - Exercise, aging and immune function.
AB  - Aging leads to a diminution of resting immune function, increasing the risk of
      infection, tumor development and auto-immune diseases. The production of
      interleukin-2 is decreased, sometimes with a decrease of total T cell count, and
      often with changes in T cell subsets and proliferative responses to mitogens.
      However, natural killer cell activity remains unchanged. In theory, moderate
      exercise should help to reverse the adverse effects of aging upon the immune
      system. However, there have been relatively few studies comparing the immune
      responses of young and older individuals to acute exercise and to training. A
      single bout of moderate exercise seems to be well tolerated by the elderly. The
      NK cell response is much as in younger individuals, but perhaps because of a low
      initial proliferative capacity, older subjects show less stimulation of
      lymphocyte proliferation by moderate activity and less suppression with
      exhausting exercise. Perhaps because resting immune function is less than in the
      young, moderate training programs seem to stimulate immune function to a greater
      extent than in young subjects. The proliferative response of the T cells is
      enhanced in elderly rodents whereas in young animals it is suppressed. Moreover,
      the resting NK cell activity of elderly human subjects seems to be increased by
      training. Nevertheless, the therapeutic use of exercise must be cautious in the
      elderly, since aging also enhances susceptibility to over-training.

PMID- 7713624
TI  - Role of beta-adrenergic mechanisms in exercise training-induced metabolic changes
      in respiratory and locomotor muscle.
AB  - To test the hypothesis that beta-adrenergic stimulation is required for the
      normal increase in oxidative capacity of respiratory and locomotor skeletal
      muscle in response to exercise training, we examined the effects of beta-blockade
      on muscle oxidative capacity in trained and sedentary rats. Thirty-four female
      adult Sprague-Dawley rats were randomly divided into four experimental groups: 1)
      trained+propranolol (TP); 2) trained + sham injection (TS); 3) sedentary +
      propranolol (SP); and 4) sedentary + sham injection (SS). Training increased (p <
      0.05) citrate synthase (CS) activity in the plantaris (+29%) and costal diaphragm
      (+12%) of TS animals compared to SS animals. In contrast, training did not (p >
      0.05) increase costal diaphragm CS activity in TP animals compared to the SS
      group. Further, although training increased (p < 0.05) plantaris CS activity in
      the TP group (+18%) compared to the SP group, the training-induced increase in
      muscle CS activity was 11% lower (p < 0.05) than observed in TS animals.
      Collectively, these results suggest that beta-adrenergic mechanisms may play a
      role in the normal training-induced increase in oxidative capacity in both
      respiratory and locomotor skeletal muscles.

PMID- 7713625
TI  - Relationship between oxygen uptake, stroke rate and swimming velocity in
      competitive swimming.
AB  - The purpose of this study was to determine the relationship between oxygen
      demand, stroke rate and swimming velocity in competitive swimmers. The subjects
      who volunteered for this study were ten trained male swimmers (age, 16.7 +/- 0.4
      yrs). VO2peak, swimming velocities at 80% (V80% VO2peak) and 100% (V100% VO2peak)
      of VO2peak and swimming velocity at the onset of blood lactate accumulation
      (VOBLA) were determined during a swimming economy profile test in a swimming
      flume. In the swimming economy test, determined by studying the relationship
      between oxygen uptake and swimming velocity cubed, the subjects were instructed
      to swim for six minutes at five or six submaximal swimming velocities. Steady
      state oxygen uptake and stroke rate were calculated during the final two minutes
      of swimming. Results indicated that there were significant correlations between
      oxygen uptake and swimming velocity cubed (r = 0.963 to 0.998, p < 0.01), between
      oxygen uptake and stroke rate (r = 0.925 to 0.998, p < 0.01) and between stroke
      rate and swimming velocity cubed (r = 0.897, p < 0.05; to 0.994, p < 0.01) for
      all subjects. Furthermore, it was found that the slopes of the regression lines
      between oxygen uptake and swimming velocity cubed and between oxygen demand and
      stroke rate were significantly correlated to swimming performance indices (V80%
      VO2peak, V100% VO2peak and VOBLA). The results of this study suggest that the
      slope of the regression line between oxygen uptake and stroke rate can be
      utilized as an effective index of evaluating swimming performance.

PMID- 7713626
TI  - Decrease of endurance performance during Olympic Triathlon.
AB  - The present study was carried out in order to quantify the athlete's endurance
      impairment after two out of three sequential events of Olympic Triathlon (OT).
      Furthermore the significance of ventilatory threshold (Tvent) and peak of oxygen
      uptake (VO2peak) as triathlete's performance predictors was assessed. Tvent and
      VO2peak were measured in six male triathletes performing an incremental treadmill
      test a week before an ad hoc triathlon event. The same test was applied
      immediately after the first two segments of the triathlon (1.5 km swim, 32 km
      bike). VO2peak and Tvent measured during the latter test were reduced compared to
      the first test. VO2peak decreased from 69 to 64 ml.kg-1.min-1 and Tvent from 58
      to 51 ml.kg-1.min-1 p < 0.01), respectively. VO2peak and Tvent measured in the
      first test were well correlated (P < 0.05) to both running and cycling times. The
      Tvent measured during the second test was related to the running time but with a
      higher significance (p < 0.01) than in the first test. The impairment in the
      endurance performance induced by the first two segments of OT is an important
      aspect to consider both in training and in race strategy. These results also
      provide evidence that VO2peak and Tvent are good predictors of triathlon
      performance at least in cycling and running events.

PMID- 7713627
TI  - Effects of naloxone opiate blockade on the immunomodulation induced by exercise
      in rats.
AB  - The purpose of this study was to examine the possible involvement of the
      endogenous opiate system in the changes in immune competence induced by isolated
      exercise. Male untrained rats were subjected to a 2.5 hours swimming exercise
      bout. Animals were killed 15 min after the end of the exercise. The concentration
      of leukocytes, lymphocytes, monocytes and granulocytes and T4 (T-helper), T8 (T
      suppressor/cytotoxic), interleukin-2 receptor (IL-2R) and transferrin receptor
      (TrfR) positive lymphocytes were determined both in peripheral blood and spleen
      by flow cytometric analysis. Exercise resulted in a significant decrease in 1)
      blood lymphocyte and splenic granulocyte number (p < 0.05), 2) blood and splenic
      T4 positive lymphocytes and T4/T8 ratio (p < 0.05), and 3) blood and splenic IL
      2R and TrfR positive lymphocytes (p < 0.05). The injection of the opiate blocker
      naloxone to exercising rats induced a decrease in the concentration and
      proportion of T8 positive lymphocytes, thereby restoring a normal T4/T8 ratio
      both in peripheral blood and spleen. Naloxone had no effect in control animals.
      The concentration and proportion of IL-2R and TrfR positive lymphocytes were not
      affected by naloxone. The mechanisms of the immunomodulation induced by isolated
      intense exercise are unclear. These data suggest that endogenous opiates
      participate in the alteration of cell-mediated immunity associated with exercise
      by modulating the T8 (suppressor/cytotoxic)-cell activity.

PMID- 7713628
TI  - Changes in several neutrophil functions in basketball players before, during and
      after the sports season.
AB  - Neutrophils play an important role in the immune system, forming the "first line
      of defence" against invading microorganisms and there are few data available
      concerning neutrophil functions in relation to exercise. We investigated in 7
      basketball professional players possible changes before, during and after the
      sports season, in some haematological parameters and in several aspects of the
      phagocytic process of neutrophils, such as adhesion, superoxide anion release and
      bactericidal activity. Training and competitions produced a significant rise in
      the number of total leukocytes and differential counts, but the values returned
      to the pre-start levels 3 weeks after the end of the championship. The
      bactericidal activity and the superoxide anion released were significantly
      greater during the sports season, while the percentage of cellular adhesion
      significantly decreased during the championship; after the sports season the
      values returned to the control levels. As in the literature data concerning
      neutrophil functions in relation to exercise are non-convergent, it is important
      in our opinion, to understand whether the alterations induced by exercise can
      persist after repeated stimuli.

PMID- 7713629
TI  - Echocardiographic size of conductance vessels in athletes and sedentary people.
AB  - The purpose of the present study was to assess the size of great and medium
      caliber arterial and venous vessels (conductance vessels) in athletes of
      different sports and sedentary people. Vessel size was measured by two
      dimensional echocardiography in 15 professional cyclists, 15 highly-trained long
      distance runners, 15 professional volley-ball players, 10 wheelchair basketball
      players, 11 wheelchair distance runners and 20 sedentary controls. The following
      vessels were imaged and measured: aortic arch, left carotid and left subclavian
      artery, right pulmonary artery, abdominal aorta and mesenteric artery, superior
      and inferior vena cava. Vessel size was considered in absolute value and
      normalized for body surface area (BSA). Among the able-bodied athletes, both
      cyclists and long-distance runners showed a generalized increase in vessels size
      in respect to controls, either absolute or normalized for BSA. The increase was
      highly significant for normalized inferior vena cava: cyclists, mean 15.1 mm, 95%
      confidence intervals 14.2 to 15.8 mm; long-distance runners, 15.8 mm, 15.3 to
      16.4; controls, 10.5 mm, 9.8 to 11.3. Volleyball players also showed larger
      vessels than controls, but this feature was clearly related to their greater body
      size because statistical differences were attenuated or abolished by
      normalization for BSA. Wheelchair athletes exhibited significantly larger upper
      body vessels but significantly smaller lower-body vessels than controls when
      normalized for BSA. In addition, wheelchair distance runners, who trained more
      intensively, had larger abdominal aorta and inferior vena cava than wheelchair
      basket players. Long-term endurance training leads to a generalized increase in
      arterial and venous conductance vessels size.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713630
TI  - Decreased torque and electromyographic activity in the extensor thigh muscles in
      chondromalacia patellae.
AB  - The alterations in thigh muscle properties of chondromalacia patellae patients
      during isometric and dynamic endurance tests were studied using a variokinetic
      knee testing system linked to surface EMG. A total of 41 patients (chondromalacia
      group) with arthroscopically certified chondromalacia of the patella were
      studied. The control group consisted of 31 healthy adult volunteers with no
      history of knee pain or trauma. Peak torque values were 21% (p < 0.01) and force
      output values 25% (p < 0.05) lower on the symptomatic side of the chondromalacia
      group than in the control group. The decrease in the ratio between integrated EMG
      (IEMG) and measured force were found in all parts of the quadriceps femoris
      muscle in patients with chondromalacia of the patella in isometric extension. No
      change in the normalized IEMG levels of the thigh muscles were found between
      chondromalacia patients and controls in dynamic endurance test. The severity of
      the chondromalacia of the patella did not affect the level of electromyographic
      activation in thigh muscles. The ratio of normalized EMG levels of vastus
      medialis and vastus lateralis did not differ between the groups. The present
      study showed that chondromalacia patellae patients have reduced force and
      electromyographic activation levels of quadriceps femoris muscle. Especially, the
      explosive strength of the quadriceps femoris muscle is reduced.

PMID- 7713631
TI  - Clinical tests versus KT-1000 instrumented laxity test in acute anterior cruciate
      ligament tears.
AB  - Forty-two patients referred to the outpatient clinic of Hagavik Orthopaedic
      Hospital within 3 weeks after an acute knee injury was found by arthroscopy to
      have a partial or total tear of the anterior cruciate ligament (ACL). In these
      patients, the results of clinical tests and instrumented laxity tests without
      anesthesia prior to the arthroscopy were analyzed. The Lachman test and the
      maximum anterior pull (150-200 N) KT-1000 instrumented test revealed abnormal
      laxity in 33 and 37 of 42 cases, respectively. Both tests revealed abnormal
      laxity more often than the KT-1000 test using 67 N (10/42) and the maximum
      anterior pull KT-1000 instrumented test also revealed abnormal laxity more often
      than the KT-1000 test using 89 N (25/42). By logistic regression analysis, the
      maximum anterior pull KT-1000 instrumented test was associated with rupture of
      the ACL (partial or total rupture). The results show that adequate anterior pull
      has to be used to overcome muscle tension to reveal abnormal laxity in acute ACL
      tears using the KT-1000 arthrometer.

PMID- 7713632
TI  - Strength and cross-sectional areas of reciprocal muscle groups in the upper arm
      and thigh during adolescence.
AB  - The purpose of this study was to investigate the development in muscle cross
      sectional area (CSA) and strength capability of the reciprocal muscle groups in
      the upper arm and thigh. Subjects were 130 boys aged 7 to 18 years; 7-9 yr aged
      group (n = 30), 10-12 yr (n = 30), 13-15 yr (n = 35), and 16-18 yr (n = 35).
      Anatomical CSAs of elbow flexors (EF), elbow extensors (EE), knee flexors (KF)
      and knee extensors (KE) were determined with a B-mode ultrasound apparatus.
      Isokinetic strength during elbow or knee extension as well as elbow or knee
      flexion was measured by using a Cybex II isokinetic dynamometer at the pre-set
      constant velocity of 60 degrees/s. The effect of age associated with a
      significant increase in both CSA and strength with a marked increase in 13-15 yr.
      The elder aged-groups had a significantly higher ratio of strength to muscle CSA
      than in the lower aged-groups. The effect of age on EF/EE CSA ratio was not
      significant, but EF/EE strength ratio was the highest in 16-18 yr and the lowest
      in 7-9 yr. With advancing age, KF/KE CSA ratio had a tendency to increase, but
      KF/KE strength ratio remained almost unchanged. These results indicate that (1)
      children in the pre-puberty or the early stage of puberty do not develop strength
      in proportion to their muscle CSA, and (2) the flexors and extensors in limbs
      have reciprocally different growth rates in either CSA or strength even in the
      same region.

PMID- 7713633
TI  - Exercise systolic arterial blood pressure in middle-aged women with normal and
      elevated arterial blood pressure.
AB  - Considerable interindividual variation in the response of blood pressure to
      exercise has been found. Factors independently contributing to this variation are
      insufficiently evaluated. This is especially true for women and older age groups.
      Reference values of progressive maximal exercise testing in middle-aged, active
      subjects, especially in women, are scarce. In this study, the response of
      systolic arterial blood pressure during a progressive maximal cycle ergometer
      test was investigated in 871 physically active female subjects aged 40 years or
      older with normal, borderline elevated and elevated blood pressure. The influence
      of 14 different subject characteristics on this response was studied: 63% of
      variation in exercise systolic blood pressure (eSBP) could be explained by work
      load, pre-eSBP, age and exercise heart rate. No difference in eSBP with
      increasing work load was found between the three groups. Subjects with higher
      exercise heart rates had higher systolic blood pressures at the same work load
      compared to subjects with lower exercise heart rates. Maximal working capacity
      (Wmax) was significantly lower in the elevated blood pressure group although
      maximal heart rate and lactate were similar. Wmax was age-dependent. Other
      subject variables were not significantly associated with eSBP. Values of eSBP for
      reference purposes are presented.

PMID- 7713634
TI  - The abuse of doping agents in competing body builders in Flanders (1988-1993).
AB  - Analytical findings of unannounced doping control in body builders in Flanders
      during 1988-1993 are reported. In some federations between 38 and 58% of the
      controlled athletes were found positive during this period. The results show that
      there was no fall in drug abuse over this period and steroids were taken even by
      body builders associated with an organisation against the use of anabolic
      steroids. In 1988 and 1989 popular anabolic steroids were nandrolone and
      testosterone. From 1990 on, a wide range of mostly injectable steroids including
      nandrolone, metenolone, drostanolone and testosterone were administered. Polydrug
      abuse including several anabolics in combination with stimulants and diuretics
      was also widespread. The beta agonist clenbuterol was detected in several urine
      samples taken in 1991, one year before its appearance in other sports.

PMID- 7713635
TI  - Blood lactate concentration following exercise: effects of heat exposure and of
      active recovery in heat-acclimatized subjects.
AB  - The purpose of this study was to examine the effect of ambient heat on the
      decrease in blood lactate concentration ([LA]bl) during passive and during active
      recovery. Ten trained men performed six 1-min bouts of exercise at 100% VO2peak
      on a cycle ergometer, with 1-min rest between the bouts. Each subject exercised
      twice in thermoneutral (22 degrees C, 40% RH, TN), and twice in hot (35 degrees
      C, 30% RH, H) conditions. Exercise was followed by either 40 min of passive
      recovery (sitting) or by 20 min active recovery (cycling at 35% VO2peak) and 20
      min passive recovery, named thereafter, 'active recovery'. Capillary blood
      lactate was measured before, 1 min after, and every 5 min during recovery. Heart
      rate (HR), rectal and skin temperatures (Tre, Tsk) were monitored continuously.
      VO2 was measured prior to exercise, during the last exercise bout, the first 10
      min of recovery, and periodically thereafter. Post-exercise [LA]bl was similar in
      all treatments (13.5 +/- 1.8, 13.0 +/- 1.3, 14.8 +/- 4.1, 13.3 +/- 2.6 mmol.l-1
      for TN-active, TN-passive, H-active and H-passive, respectively). [LA]bl was
      significantly lower during active, compared to passive recovery in both, TN and H
      conditions. Environmental heart did not independently affect [LA]bl during
      passive or active recovery. Exercise resulted in an elevation in Tre in all
      treatments, with a significantly higher Tre during active recovery in H compared
      to the other sessions. Likewise, no differences in HR and in VO2 were observed
      between H and TN conditions during active nor during passive recovery.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7713636
TI  - Growth of hand-reared American kestrels I. The effect of two different diets and
      feeding frequency.
AB  - Seventy captive-bred American kestrels (Falco sparverius) were hand-reared on
      diets of either day-old cockerels (Gallus domesticus) (n = 38) or laboratory mice
      (Mus musculus) (n = 32) at meal frequencies of 4 or 6 times per day. Ad libitum
      food was provided in all meals. A proximate analysis of the two diets was
      performed and showed that cockerels when compared to mice contained more crude
      protein (60.0% versus 42.7% dry matter) and less fat (28.1% versus 46.5% dry
      matter). Body mass of nestlings was recorded daily until fledging, while lengths
      of the antebrachium and 9th primary remex were measured at intervals of 2 to 5
      days. Data were fitted to the Richards growth model. Cockerel-fed nestlings
      exhibited growth patterns similar to those found in free-ranging kestrels. Mouse
      fed birds however, grew more slowly which could be related to inadequate protein
      intake. No effect of hand-feeding frequency (4 versus 6 times daily) on growth
      rates was noted under any of the two diets. Irrespective of the dietary group,
      female kestrels were significantly heavier at the end of the experiment, as
      expected from the reversed sexual size dimorphism present in adult American
      kestrels.

PMID- 7713637
TI  - Growth of hand-reared American kestrels. II. Body composition and wingloading of
      fledglings hand-fed two different diets.
AB  - The body composition of young American kestrels (Falco sparverius) hand-fed
      either a protein-rich diet (day-old cockerels Gallus domesticus) or a fat-rich
      diet (laboratory mice Mus musculus) was determined one day after fledging. Mouse
      fed fledglings (n = 16) had significantly greater fat deposits than cockerel-fed
      birds (n = 15), while the crude protein content of the carcass was unaffected by
      the diets. At fledging, mouse-fed birds showed a significantly greater
      wingloading than cockerel-fed birds. Larger fat reserves (as in mouse-fed birds)
      might be mobilised in the event of a food shortage and thus these birds would be
      at an advantage in relation to fledglings with smaller reserves. On the other
      hand, large fat deposition, which alters wingloading, might impair the flight
      performance of the fledglings.

PMID- 7713638
TI  - An analysis of the orientation of the radiographic trabecular pattern in the
      distal radius of children.
AB  - A digital image processing system was used to study changes in orientation of the
      radiographic trabecular pattern of bone in children aged 4-14 years. The
      radiographs originated from a mixed-longitudinal growth study (The Nijmegen
      Growth Study), which comprised of three birth cohorts and which was carried out
      between 1971 and 1975. Of 3075 left hand-forearm radiographs of 426 children, the
      orientation of the trabecular pattern of the radius was analysed in twelve
      directions on a standard area of 10 x 10 millimetres. It was demonstrated that
      the trabecular pattern of the radius shows two predominant directions of
      orientation: along and perpendicular to the long axis of the radius. Spearman's
      Rank Correlations were calculated between direction of orientation and age of the
      children for the total population as well as for the cohorts separately, because
      the existence of cohorts-effects. The cohort of the youngest children showed more
      and higher significant correlations than the other cohorts, indicating that the
      trabecular pattern of young children is more subjected to changes. The results
      indicate that the prevalence of trabeculae orientated perpendicular to the long
      axis of the radius decreases. We speculate that this development reflects the
      effects of changes in mechanical loading in that direction during growth and
      development resulting in functional adaptation of the trabecular bone.

PMID- 7713639
TI  - Longitudinal changes in the orientation of trabecular bone in relation to the
      location in the distal radius.
AB  - The aim of this study was to examine changes in orientation of trabecular bone
      during growth and development in relation to the location of trabeculae between
      the epiphysial growth plate and the marrow cavity. Five annual hand-wrist
      radiographs of 57 children between 4-9 years of age, originating from the
      Nijmegen Growth Study, were analysed by a digital image processing system.
      Analysis was carried out on four adjacent areas of 7 mm x 7 mm located in the
      distal head of the radius between the epiphyseal growthplate and the marrow
      cavity. The orientation of the trabecular pattern was measured in twelve
      directions. The orientation of trabeculae at a standardized distance from the
      epiphysial growth plate did not change significantly during growth and
      development. The orientation in directions perpendicular to the long axis of the
      radius was higher in newly formed trabecular bone, which is located just below
      the epiphysial growthplate, than in older trabecular bone at a larger distance
      from the epiphysial growth plate. Observation of one single area during five
      years of growth and development showed a comparable development.

PMID- 7713640
TI  - Growth and embryonic development and aging. National Library of Medicine MEDLINE
      search.

PMID- 7713641
TI  - The stranger in the house.
AB  - Concepts precede facts, and the hypotheses of psychoanalysis are foreign to the
      way most people think: it is not known, Freud says, whether they should be
      regarded as 'postulates or as products of our researches'. To guess (which
      translates the German verb: 'zu erraten') may be the only way to represent to
      oneself what is happening, because what is happening happens in the transference;
      and transference is the only formation of the unconscious the patient can tell us
      nothing about. To guess and to construct are synonymous and, in our
      constructions, we communicate our guessing to the patient using a kind of
      intermediate language, which is the uncanny language of transference neurosis
      and, at the same time, the language of conceptualisation; that language
      acknowledges the strangeness and foreign nature of transference. When it does
      not, theory then becomes coded and lifeless. And its concepts are in danger of
      resembling what the Editorial of the first issue of the 'International Journal'
      in 1920 called 'catchwords'. Theory should remain for us, Freud said, 'a stranger
      one has not invited'.

PMID- 7713642
TI  - The conceptualisation of clinical facts.
AB  - There has never been a fact that has not already been conceptualised. To enter
      into discourse as a fact, whatever the case may be in the world that is of
      immediate concern must always already be symbolically mediated, that is, already
      a specialised version of that aspect of the world. To become a 'clinical' fact,
      however, 're'conceptualisation is required; before then the clinician has only
      details. Details become clinically significant when, implicitly or explicitly,
      they are situated and redefined in a context of interrelated clinical narratives.
      These narratives are based partly on dialogue and partly on the general theories
      or metanarratives provided by one or another school of psychoanalytic thought.
      During psychoanalysis, new clinical facts continue to be conceptualised, and
      these often alter their own formative contexts, for they include the consequences
      of previous conceptualisations. Consequently, facticity is always in flux as,
      over time, understanding alters meaning and emphasis. Even the apparently brute
      fact of corporeality changes with changes of age, culture, historical epoch,
      gender of patient, and phase of analysis. In analysis, a central role is played
      by insight into the functions served by the analysand's uses of 'fact' in the
      course of devising, unconsciously, transferenceAcountertransference enactments.
      Illustrated case material is provided.

PMID- 7713644
TI  - Conceptualisation of the clinical psychoanalytical fact.
AB  - The author tries to describe and illustrate clinically two levels of abstractions
      made in the conceptualisation of 'clinical psychoanalytical' facts. The first
      one, immediate, occurs in the 'here-and-now' of the emotional experience which
      develops in the session and where unconscious and preconscious aspects of the
      analyst predominate, particularly those resulting from his unconscious
      theoretical reference scheme. The second level of abstraction, mediate, is made
      after the session and, even if it includes elements from the previous level, is
      characterised predominantly by the presence of rational, conscious elements,
      which allow the formulation of more general theoretical concepts and broader
      articulations of the patients' associations with one another, with the session as
      a whole, with that moment in the analysis, with the patient's history and with
      different theoretical references.

PMID- 7713643
TI  - Conceptualisation of clinical facts in the analytic process.
AB  - In this paper the author discusses what she understands to be a clinical fact,
      stressing that it takes place within the analytic situation between patient and
      analyst. It is in the process of conceptualising the fact that the analyst comes
      to define it. In order to conceptualise, the analyst must have a frame of
      reference, a theoretical basis through which he perceives his patient's
      communications and is able to give meaning to them. In analytic work, the analyst
      uses his theory in mainly two ways. When working with his patient it operates
      mostly unconsciously, but interspersed by quick more conscious thinking. When
      away from the patient, theory needs to come to the front of the analyst's mind,
      consciously used by him. A clinical case is used to illustrate these two aspects
      of theoretical work. In the material presented, aspects of a first session are
      tentatively conceptualised. Then material from the same patient some years later
      is described, the method of working and the way of understanding is discussed and
      thus the process of conceptualising can be illustrated. The theme of hope has
      been singled out as a linking point between the earlier and later pieces of
      material.

PMID- 7713645
TI  - On formulations to patients.
AB  - For the author, the psychoanalytic clinical fact can only be an arbitrary
      fragment detached from the totality of the situation, which alone specifies it
      and which comprises the different forms of formulations that are proposed to
      patients. Using the difference established by Freud between what is and what is
      not analysable as a starting point, he distinguishes between two radically
      different analytic situations. To illustrate, he extracts, from the same cure, a
      'fact' constituted of two moments; one 'this side of analysability, the other at
      its limits. He calls 'homogeneous' the neurotic moment in which transference and
      countertransference are similar in nature, and he calls 'heterogeneous' the
      'limit' situation in which predictabuity is absent, and in which change, when it
      occurs, is one of divine surprise. The author advances an hypothesis on the
      factors at work in the changes that subsequently occurred, particularly in the
      case of the 'limit' situation, drawing from the therapeutic experience of the
      'psychoanalytic psychodrama' and from the work of Jean Laplanche. A single
      generating principle would thus be involved, based on the action of the
      unconscious seduction contained in the unknowable, 'enigmatic', part of verbal
      and nonverbal messages, it grounds its transforming action in the following
      sequence: unconscious seduction, limited traumatic penetration, symbolisation,
      i.e. the emergence of meaning in the aftermath.

PMID- 7713646
TI  - Interpretation: selected fact or overvalued idea?
AB  - The authors describe Bion's use of the notion of the 'selected fact' in the
      evolution of analytic interpretations. They draw attention to the similarity
      between the emergence of a 'configuration' from a selected fact and the
      crystallisation of delusional certainty from an 'overvalued idea'. The risks to
      the patient of the imposition of an overvalued idea is described. They emphasise
      the importance of monitoring the subsequent development in sessions following
      interpretations for evidence of conscious and unconscious reactions to it and
      offer clinical examples of the use of a selected fact in arriving at an
      interpretation and the unconscious use of an overvalued idea to form an
      interpretation and the subsequent analysis of its effects.

PMID- 7713647
TI  - Transformations.
AB  - In this paper, through the microanalysis of a session of a very disturbed
      patient, the author attempts to underline the relevant importance of the
      formulation of the interpretation, which should not be split off from its
      content. He thinks that the psychoanalysis of these closing years of our century
      is characterised by a redefinition of the object of its study; that is, the
      particular intersubjective figure constituted by the analyst-patient
      relationship. In his view, the interpretation emerges from the analyst's capacity
      to contain and adequately transform the unbearable experiences of his patient's
      mental life reproposed in the analytic relationship. This internal transformative
      process of the analyst--Rosenfeld's 'function of putting experiences into words'-
      can be assisted linguistically. A careful analysis of the levels or channels of
      discourse, and an accurate study of certain linguistic notions, can prove to be
      of great assistance in formulating interpretations and in contributing to enhance
      their effectiveness. The author has tried to give examples of some of these ideas
      in the discussion of the clinical material, while keeping in mind that the
      activity of the analyst is very close to that of the artist.

PMID- 7713648
TI  - Formulation of interpretation. From truth to experience.
AB  - The task of formulating an interpretation is discussed in terms of seeing it as
      the analyst's search to make the interpretation relevant to that specific point
      in the analytic process, in order to make it into something that can be felt by
      the patient as true and meaningful. Illustrations from the literature from Freud
      onwards are used to show how this search has been part of the history of
      psychoanalytic technique, which is still ongoing in order to make our newer
      understandings into something meaningful and therapeutic for the patient. One
      area that is particularly emphasised in this paper is the need to include
      consideration of the patient's relationship with his body as part of the analytic
      understanding in order for the patient to be able to experience an interpretation
      as having affective meaning and to create a link to external reality.

PMID- 7713649
TI  - Formulations to the patient: explicit and implicit.
AB  - Many of our formulations to the patient are conveyed through the day-to-day
      unremarkable actions, verbal and nonverbal, occurring between analyst and patient
      as the analyst attempts to understand his patient within the analytic setting.
      The analyst's confidence, even intensity, concerning the value of analysis is
      significant in enabling him to communicate successfully with his patient. Unlike
      what may have been the case in the past, this analytic fervour is not in the
      service of a single theory or an attempt to prove an analytic proposition, but is
      aimed at deepening introspective curiosity and opening avenues of communication.
      Within our characterologic and procedural limits, we use ourselves in a large
      variety of ways in an attempt to further the analytic process. This use of
      ourselves, conveyed to the patient in innumerable interactions, becomes a central
      analytic fact that fosters the patient's participation in his analysis. Clinical
      vignettes are provided to illustrate these propositions.

PMID- 7713650
TI  - On formulating clinical fact to a patient.
AB  - This paper approaches the issue of formulation to the patient by examining the
      interpretations offered to one patient concerning her reactions to three analytic
      holiday breaks. Detailed material from several sessions is presented in the
      context of the author's attempt to try to understand how she arrived at what she
      said and understood and how the interchange with her patient developed. The
      author suggests that the material shows a gradual deepening both in her
      understanding and in her patient's insight into the patient's responses to being
      left; to recognising that her analyst was pursuing an independent life of her
      own; and to becoming aware of her unconscious beliefs about her analyst's
      unconscious motives for leaving. The author concludes that her method of arriving
      at formulations varied. Generally speaking, conceptualisation of clinical facts
      does precede formulation to the patient and is then succeeded by validation or
      non-validation. In one instance, however, formulation, guided perhaps by an
      unconscious hunch on the part of the analyst, preceded conceptualisation. This
      particular formulation also led to far-reaching and integrating interpretations.
      The implication is that there are several methods of arriving at valuable
      formulations of clinical fact, none of which should necessarily be privileged.

PMID- 7713652
TI  - Validation in the clinical process: four settings for objectification of the
      subjectivity of understanding.
AB  - Clinical material is presented for discussion with the aim of exemplifying the
      author's conceptions of validation in a number of sessions and in psychoanalytic
      research and of making them verifiable, susceptible to consensus and/or
      falsifiable. Since Freud's postscript to the Dora case, the first clinical
      validation in the history of psychoanalysis, validation has been group-related
      and society-related, that is to say, it combines the evidence of subjectivity
      with the consensus of the research community (the scientific community).
      Validation verifies the conformity of the unconscious transference meaning with
      the analyst's understanding. The deciding criterion is the patient's reaction to
      the interpretation. In terms of the theory of science, validation in the clinical
      process corresponds to experimental testing of truth in the sphere of inanimate
      nature. Four settings of validation can be distinguished: the analyst's self
      supervision during the process of understanding, which goes from incomprehension
      to comprehension (container-contained, PS-->D, selected fact); the patient's
      reaction to the interpretation (insight) and the analyst's assessment of the
      reaction; supervision and second thoughts; and discussion in groups and
      publications leading to consensus. It is a peculiarity of psychoanalytic research
      that in the event of positive validation the three criteria of truth (evidence,
      consensus and utility) coincide.

PMID- 7713651
TI  - Validation in the clinical process.
AB  - Validation has several meanings in psychoanalysis. The scientific validation of
      psychoanalytic theories or of clinical effectiveness can be contrasted with
      validation in the clinical process. Originally, this referred to the external
      confirmation of specific memories or reconstructions. Recently, interest has
      shifted to the impact of the analyst's interventions on the analytic process. The
      analyst's quest for validation may lead to overemphasis on specific features of
      the analytic data, or an episodes of invalidation. The analyst's response to the
      latter is an important aspect of psychoanalytic technique.

PMID- 7713653
TI  - Developing a grounded hypothesis to understand a clinical process: the role of
      conceptualisation in validation.
AB  - This paper argues the case that validation in the clinical process depends to a
      large extent on being as clear and specific as possible about the hypotheses
      being put forward. In sessions interpretations are made based on intuitive and
      quite spontaneous links arising from background orientations and what will be
      called clusters of observed clinical facts. Outside the session, a wider and more
      developed set of grounded hypotheses can be developed, intended to illuminate
      what seem to be the core issues that arise over time and the core problems
      suffered by the patient. Often such hypotheses will only be in the form of
      working orientations. If they can be conceptualised more precisely into specific
      hypotheses explaining sets of observed events and predicting consequences, they
      can be better evaluated--either by the analyst working alone, or in group
      discussion through the achievement of genuine consensus. A process of building up
      a 'grounded' hypothesis, by making comparisons in the process of trying to solve
      a clinical problem, is described using detailed clinical material. This is also
      intended to illustrate the argument that it can be useful to consider the basic
      occurrences reported from sessions as data, distinct from the theory put forward
      to explain them.

PMID- 7713654
TI  - Validation in the clinical process.
AB  - The combined analysis of the predominant themes, (a) in the patient's
      communication of his subjective experience, (b) in the patient's nonverbal
      behaviour and linguistic style, and in (c) the countertransference, provide
      indications for the main focus of the analyst's interpretive work, as well as
      potential evidence, in the corresponding changes in those three areas, of
      confirmatory or disconfirmatory aspects of the patient's reaction to the
      interpretation, thus providing the material for validation of the interpretation
      in the analyst's mind. Exploring a patient's responses to his interpretive
      interventions in the light of these criteria permitted the author to validate one
      interpretation at a 'right level in the right moment', to discard other
      interventions as too superficial, and to characterise one interpretation as
      probably premature.

PMID- 7713655
TI  - The publication of clinical facts: a natural-science view.
AB  - Authors face a variety of obstacles to publication after submitting their papers
      to scientific journals. The first of these derives from the meaning of the word
      'fact' and the phrase 'clinical fact'. A second arises from the ambiguous nature
      of the analysing instrument used to accumulate clinical data. A third is a result
      of the different perspectives used by analysts to inform their observational
      instruments. The fourth impediment is a cognitive one: there are often serious
      lapses in logical operations involving predicate identifications and hasty
      generalisations. The fifth is a result of an awkward contemporary glossary, a
      glossary that extends ambiguities rather than relieves them. Finally, there is an
      obstacle that derives from style.

PMID- 7713656
TI  - Publication anxiety: conflict between communication and affiliation.
AB  - The author suggests that publication anxiety is ubiquitous and natural; it can
      produce inhibition, symptomatic disorders of the text, or simply overt anxiety.
      Anxiety-free publication occurs where anxiety is denied as part of a manic
      defence which produces complacent orthodoxy, triumphant iconoclasm, or an
      illusion of originality. A discriminating journal usually detects this and
      publication fails. If the anxiety is excessive, there may be an inhibition of
      publication such as afflicted Darwin. Lesser degrees of anxiety may result in
      distraction or distortion due to a compromise between the urge to communicate an
      idea and the desire to consolidate affiliation with a significant group through
      shared language, common belief systems, totemic figures or ritual utterances. The
      author sees this conflict as internal to the individual. It is shaped by Oedipal
      anxieties which are given different emphasis and intensity by the scientific
      contexts current at the time. If the 'paradigm', under the influence of which the
      analyst is writing is in the ascendant, publication is relatively free of anxiety
      for most writers who are content to add to its application. Some, however, suffer
      'anxiety of influence', fearing that their existence as originators of ideas is
      threatened. When the stability of the paradigm is threatened, due to the
      accumulation of anomalies, publication anxiety, with both persecutory and
      depressive elements is intensified. This increases the conflict between the need
      for affiliation and the desire for communication and may result in defensive
      writing or distorted texts.

PMID- 7713657
TI  - Psychoanalytic facts: from the editor's desk.
AB  - The editor's vantage-point adds additional requirements to our concept of a
      psychoanalytic fact. The data of the psychoanalytic experience must pass peer
      review and enlist the conviction of the editors that what is asserted holds up to
      the general conceptions of truth within the context of the profession. Issues
      that converge on this process are reviewed, including how analysts report data,
      the context of discovery, and the adequacy of the written report as a convincing
      new contribution. Recent developments in the United States that bear on these
      matters are reviewed.

PMID- 7713659
TI  - Publication of clinical facts.
AB  - This article explores a correspondence between the conduct of clinical
      psychoanalysis and the publication of clinical facts in the psychoanalytic
      literature. At issue in both activities are the nature of psychoanalytic
      understanding and the way psychoanalytic understanding is communicated. An
      analyst intervening in the treatment situation offers an interpretation to a
      patient; an analyst publishing a clinical case report offers an interpretation to
      colleagues. How can we best judge the validity of an interpretation in either
      instance? How do we conceptualise the accuracy of a published clinical fact in
      the light of the observing analyst's irreducible subjectivity? Is disguise for
      the purpose of preserving confidentiality acceptable in the publication of
      clinical facts? These and related questions are taken up, using an illustrative
      clinical vignette as a basis for discussion. The publication of clinical facts
      drawn from systematic empirical research studies is compared with the publication
      of clinical facts drawn from observations made by single treating analysts.

PMID- 7713658
TI  - A case is not a fact.
AB  - Why do we publish clinical data? Between the scientistic illusion that assumes
      that cases are objective data and the disillusioned observation that
      psychoanalytic literature is mainly used to boost identity feelings, what role is
      played by such publications? New psychoanalytical knowledge results from clinical
      practice and not from scientific experiments or observations. A clinical
      vignette, even more than a full monograph, is clearly not designed to prove a
      theory from objective facts but to illustrate a particular clinical view. The
      quality of a case report relies on at least three criteria: data economy;
      adequacy to the proposed thesis; and convincingness or persuasion. A case is not
      a fact, because understanding it presupposes 'semantic holism': understanding any
      mental state requires taking into consideration a 'world of knowledge'. Empathy
      results from an unlimited work of inferences. In presenting a case, the
      psychoanalyst is always in a sense a 'thought-reader'. He describes what he
      believes he discovers.

PMID- 7713660
TI  - Intimacy and science: the publication of clinical facts in psychoanalysis.
AB  - This paper starts by stating that in science there are no facts independent of
      theory. In psychoanalysis, the theory of the decisive importance of the
      unconscious makes it possible to grasp clinical facts. This leads to the
      centrality of transference in analysis. The latter is understood as a social
      fact. Transference, perceived as a private experience, can be known in the
      intimacy of the psychoanalytic relationship, through the communication by means
      of language, which is public. Psychoanalysis is then considered a science of
      intimacy. The analyst, in publishing clinical facts, faces the problem of the
      transposition of a fact from the intimacy sphere, considered as private, to the
      public sphere, and thus serves a scientific purpose. A treatment report is
      presented to illustrate the problems of the registering, editing and publishing
      of clinical facts, based on the parallel between making conscious that which is
      unconscious and making potentially public what is private. Thus the analyst
      confronts similar difficulties and anxieties, when publishing clinical facts, as
      the ones that the analysand must overcome to know, through the social experience
      of psychic intimacy, his or her private inner world.

PMID- 7713661
TI  - Herbert S. Gaskill, M.D. (1909-1993).

PMID- 7713662
TI  - Symmetry: Matte-Blanco's theory and Borges's fiction.

PMID- 7713663
TI  - Origins of consciousness.

PMID- 7713664
TI  - The conceptualisation and communication of clinical facts in psychoanalysis.
      Special 75 anniversary edition.

PMID- 7713665
TI  - The conceptualisation and communication of clinical facts in psychoanalysis.

PMID- 7713667
TI  - 'The Tower of Babel' or 'after Babel in contemporary psychoanalysis'? Some
      historical and theoretical notes on the linguistic and cultural strategies
      implied by the foundation of the International Journal of Psycho-Analysis, and on
      its relevance today.
AB  - The author uses private correspondence and documents referring to the foundation
      of the 'International Journal of Psycho-Analysis' and the 'Glossary' for
      translating Freud's work, to try to delineate the political and cultural strategy
      of Jones in founding and developing the 'International Journal of Psycho
      Analysis'. Both strategies were based on the wish to have administrative and
      cultural control of psychoanalysis in the English-speaking countries. In the end
      Jones and his colleagues succeeded in making the language they created the
      official language of the IPA; through control of Freud's translations, through
      the 'Glossary' and particularly through its diffusion in the 'Journal'. The
      author briefly illustrates the various cultural sources of this attempt and tries
      to show the similarities between the project of Jones and the first generation of
      pioneers of psychoanalysis in Great Britain and the myth of the tower of Babel-
      one of its most important foundation stones being the 'International Journal'.
      Finally, the author stresses that those issues are still extremely alive in
      psychoanalysis today. But, confronted with the near-Babel of languages of
      contemporary psychoanalysis, can we still imply the existence of this universal
      common language and use it? Can the 'International Journal' still maintain its
      hegemony? Do we really understand each other even when we use the same technical
      terminology in English? Or shall we accept that today we should live without a
      tower of Babel in psychoanalysis? The author concludes that there is some hope,
      provided that we do not pursue meanings to the forbidden limit of the absolute.

PMID- 7713666
TI  - The confusion of tongues and psychic trauma.
AB  - 'The confusion of tongues' characterised the polarised dimensions of the closing
      Ferenczi/Freud communication, and extended to problems of psychoanalytic
      formulation and publication. There were manifest and latent issues which remain
      of historic importance. Ferenczi was dying and assumed Freud was dying when he
      wrote this classic essay, so relevant to contemporary psychoanalytic thought and
      controversy. Denying and sometimes acknowledging his progressive, fatal illness,
      Ferenczi made enduring contributions to the understanding of child abuse and
      trauma while severely traumatised. Concepts of trauma and countertransference
      were amplified and expanded. Freud remained remarkably creative while physically
      declining with oral cancer; Ferenczi manifested progressive and regressive
      trends, fostering both sublimated innovation and wild analysis. Psychoanalysts
      tended to avoid, for half a century, confronting the problems of the ill,
      impaired, and dying analyst. The clarification of 'The confusion of tongues'
      continues in contemporary psychoanalytic discussion and debate. The paper
      presaged a widened interest in the analyst's analysing functions, unconscious
      communication, countertransference, and the interplay of reality and fantasy
      inside and outside the psychoanalytic situation.

PMID- 7713668
TI  - What is a clinical fact?
AB  - The author approaches the problem of defining what a clinical psychoanalytic fact
      is by proposing that there is such a thing as a 'psychoanalytic apparatus'--a
      working psychoanalysis--the proper functioning of which is revealed by the
      presence of certain emotional states. One of these is the presence of a sense of
      intimacy shared by patient and analyst within the analytic relationship, combined
      with a simultaneous sense of isolation of the participants. Another is a painful
      conflict engendered by the beauty of the analytic experience, similar, but not
      identical to a negative therapeutic reaction. He goes on to suggest that, when
      this apparatus is working properly (i.e. when psychoanalysis is occurring), both
      analyst and patient find that they gain a type of conviction about the patient's
      psychic reality or inner world that can only be obtained in analysis. The
      patient's psychic reality is therefore the domain of psychoanalytic clinical
      facts. The author concludes by proposing that, despite appearances to the
      contrary, this type of definition of a clinical fact can be used in a rigorous
      scientific manner, and he briefly discusses what is required to do so.

PMID- 7713670
TI  - Is that a fact? Empiricism revisited, or a psychoanalyst at sea.
AB  - In this paper, the author has tried to illustrate a few of the long, tortuous,
      and illusive workings by which an analyst, in constructing the configurations
      called 'facts', tries to combine the perspectives, traditions, and methods of
      humanism and science, and to move from the subjectivities of observation,
      character, experience, and theory toward the goal of a relatively informed
      subjectivity. He has tried in particular to illustrate: (1) Characteristic
      sequences of trial and error, and some events of observation of self and other,
      that lead again and again to corrections, modifications, and expansions of our
      previous constructions of 'facts'. (2) Aspects of our struggles to find ways to
      be guided by our theories and our other suppositions and predilections, but to
      the degree possible, when possible, not driven. (3) Aspects of a personal
      perspective--attention to a patient's hidden questions--by which the author tries
      to identify facts of the surface that may help him to help his patients to
      advance their self inquiries and to bridge to some facts of the depths that have
      contributed to the shape of those facts of the surface.

PMID- 7713669
TI  - The special nature of psychoanalytic facts.
AB  - Psychoanalytic facts are almost always capable of being put into words and they
      include things the patient tells us, things we tell the patient, and things we
      tell our colleagues. They include various combinations of observation and theory,
      evidence and hearsay, dream and reality. In contrast to the more usual facts of
      the everyday world, a psychoanalytic fact is almost never based on pure
      observation and it is partly for this reason that a dispute over facts frequently
      conceals a dispute over theory. It also follows that bare facts are almost never
      presented by themselves; when they are presented (as in a publication), they are
      almost never quite the same as when experienced in the session. Some meanings are
      lost in publication; others are inadvertently added by the reader, as he tries to
      fill in the gaps of a vague report. 'Clinical' facts (which have just been
      described) should be distinguished from 'contextual' facts, which colour the way
      we hear the patient's reports, and from 'latent' facts, which cannot be detected
      by the analyst in the session but must be measured by other techniques. Because
      the proportion of theory to observation is probably greater in clinical facts
      than in latent facts, the latter may provide more reliable measures of a clinical
      happening. Greater reliance on latent facts may also reduce our dependence on
      metaphor and smooth the transition from clinical moment to published account.

PMID- 7713671
TI  - What is a clinical fact?
AB  - As a preliminary to the question, 'What is a clinical fact?', the author asks the
      wider question, 'What is a fact?', answering that facts are double in aspect:
      they both say how the world is, and they also depend on our species, our
      language, theory, etc. A claim of fact in any empirical discipline--in the
      natural sciences or in human studies with their different methods--is a truth
      claim which is not infallible or unique to the fact, and also a claim that must
      offer itself for verification. Using the clinical record of three sessions, she
      then tries to answer the question, 'What is a clinical fact?', offering the
      starting formulation that clinical facts, under the unusual conditions of an
      analytic hour which give an analyst access to a patient's inner world, manifests
      themselves in the form of immediate psychological realities between patient and
      analyst. On the way, the author discusses the analyst's anxieties about making a
      claim of clinical fact; further striking features emerge about clinical facts in
      the three sessions, and some unsolved problems, i.e. the variety of analytic
      theories, subjectivity and objectivity, are noted. Even while they bear the
      perplexities of their problems, clinical facts are of great significance to the
      study of the mind. They extend the domain of psychology to the area of the mind's
      interiority, with its human experiences of subjective meaning, conscious, and
      especially unconscious.

PMID- 7713672
TI  - What is a clinical fact? Clinical psychoanalysis as inductive method.
AB  - This paper is an inquiry into the nature of clinical facts in psychoanalysis. The
      attainment of representability of psychic reality being requisite for insight,
      the author examines inductive processes on the part of both analyst and
      analysand, which are to be considered proper aspects of the study of clinical
      facts. It is argued that the analyst chooses his interpretations guided in good
      measure by nonverbal material, based on how he intuits that he is 'used' by the
      analysand and the ways the analysand feels 'used' by him; such nonverbal clues on
      the nature of the unconscious relational 'frames' operating in sessions guide him
      to select relevant associations from the universe of the analysand's verbal
      utterances. He thus comes to voice his interpretations, purveying a 'mapping' of
      psychic reality that typically makes use of a new viewpoint for description.
      Insight is achieved when the analysand attains ostensive refutation or
      redefinition of his unconscious 'theories' about the relationship, and this
      happens only in concrete individual situations, when the effects of his
      relational unconscious 'theories' come to be contrasted observationally in
      diverse 'screens', perceptual and mnemic, against the background of the analyst's
      neutrality: in such a way unconscious 'theories' attain the Pcs.-Cs. domain of
      the 'no'.

PMID- 7713673
TI  - Clinical facts or psychoanalytic clinical facts?
AB  - A clinical fact is defined by the field in which it is situated. In the field of
      psychoanalysis, the author makes a distinction between psychoanalytic clinical
      facts arising outside the analytic situation, for example, during interviews or
      in the applied psychoanalysis, and psychoanalytic clinical facts arising within
      the psychoanalytic situation, where they find their full value in the
      transference and countertransference relationship. The author gives two
      illustrations of this. The characteristics of psychoanalytic clinical facts are
      that they are observable and communicable, and that they have at the same time a
      fixed and a transformational aspect. During a preliminary interview it is
      fruitful to use psychoanalytic clinical facts to open the patient to his/her
      psychic life through contact with the psychoanalyst.

PMID- 7713674
TI  - On the conceptualisation of clinical facts in psychoanalysis.
AB  - After defining 'facts', 'clinical facts' and 'psychoanalytic clinical facts' the
      authors describe their conceptualisations of these facts from experience-near to
      experience-distant levels. They maintain that psychoanalytic clinical facts are
      jointly created by patient and analyst and are to a great degree dependent on the
      analyst's mode of observation and theory. They illustrate the various levels of
      conceptualisation within the broad outlines of self psychology with three
      detailed clinical vignettes from the analysis of Mr K. A starting central
      question in the authors' minds arises out of their focus on the patient's
      selfobject transference (in this instance a mirror transference), hence on the
      function they serve for the patient in this transference; the role he assigns to
      them in the restoration and maintenance of the cohesiveness of the self. It is
      the recognition of this function that serves as the basis for their
      conceptualisation of the patient's psychopathology as well as the curative
      process of his analysis.

PMID- 7713675
TI  - Comments on the conceptualisation of clinical facts in psychoanalysis.
AB  - Perception is an active process involving a complex system of perceptual and
      cognitive structures. Facts reflect the ways in which we organise the data
      received by our senses, and this organisation is highly selective. The private
      theories of psychoanalysis play a major role in the organisation of facts and in
      their conceptualisation. It is important that there should be more attention to
      clinical theories and technical frames of reference, and as an illustration of
      this a clinico-technical conceptualisation which has been found useful is
      presented in some detail. This makes use of the concepts of the present and past
      unconsciouses, in this way emphasising the topographical dimension which had come
      to be under-stressed in Freud's structural theory and in subsequent ego
      psychology. The past unconscious can be regarded as a sort of 'template'
      (structures, rules, schemata, etc.) developed in the child in the first few years
      of life. This contributes to the form of fantasies and behaviour arising in the
      depths of the present unconscious, in which system such representational content
      is acted on by defences and other mechanisms to prevent 'child-like' content from
      disrupting the older individual's equilibrium. The censorship between the present
      unconscious and consciousness is considered, and the view taken that the primary
      focus of the analytic work is in relation to this censorship. The links between
      the analytical aim of making previously unacceptable mental content acceptable to
      the individual, on the one hand, and the roles of construction and
      reconstruction, on the other, are discussed in relation to psychoanalytic
      technique.

PMID- 7713676
TI  - [The occupation variable as indicator of work conditions].

PMID- 7713677
TI  - [Induced abortions among Spanish women in England and Wales (1974-1988)].
AB  - To assess the importance of travelling for abortion in Spanish women from 1974 to
      1988, a descriptive epidemiologic study was undertaken, based on information from
      the United Kingdom Office for Population Censuses and Surveys. Additionally, the
      effect of the democratic restitution in Spain (1978) and of the passing of the
      Spanish abortion law in Spain is explored. During the study period, close to
      200,000 Spanish women travelled to England and Wales to have an abortion. The
      annual figures range from 2,978 in 1974 to 22,002 in 1983. In 1988, in spite of
      the partial decriminalization of abortion in Spain, still 3,188 travelled to the
      UK for an abortion. In average, 1 out 35 Spanish women in fertile ages travelled
      to England and Wales for this reason in the study period. The likelihood was
      higher for the cohort of women born between 1955 and 1959, for which the risk was
      4.5%. The proportional distribution by age shows that teenagers increased their
      relative importance from 9.3% in 1974 to 17% in 1988, suggesting less benefits
      for this age group than for older women from the democratization of the country
      and the abortion law.

PMID- 7713678
TI  - [Proposed method to estimate underreporting of induced abortion in Spain].
AB  - In Spain, from 1987 to 1990 the rate of legal abortion reported to the health
      authorities has doubled; nevertheless, the observed geographical differences
      suggest to an underreporting of the number of voluntary pregnancy terminations.
      Based on information on several sociodemographic, economic and cultural
      characteristics, contraceptive use, availability of abortion services, fertility
      indices, and maternal and child health status, five homogenEous groups of
      autonomous region were identified applying factor and cluster analysis
      techniques. To estimate the level of underreporting, we assumed that all the
      regions which shape a cluster ought to have the same abortion rate that the
      region with the highest rate in each group. We estimate that about 18,463
      abortions (33.2%) were not reported during 1990. The proposed method can be used
      for assessing the notification since it allows to identify geographical areas
      where very similar rates of legal abortion are expected.

PMID- 7713679
TI  - [Identification of problems and needs in health: description of a participative
      experience in primary care].
AB  - OBJECTIVE: To identify health problems and needs from a Health area population.
      To detect inequalities in relation with sociodemographic variables. METHODS: An
      observational descriptive study, cross-sectional study, qualitative research.
      SETTING: A Health area in Cordoba divided in three different areas: residential,
      inner city and rural area. We select three different groups of population and the
      following instruments of measurements: a) general population older than 15 years
      old (survey by interview completed door-to-door and personally) (N = 12,801)
      (coverage = 96.6%); b) Representatives of the community (N = 47), by Delphi
      technique (answering rate = 62.5%) and Nominal Group technique applied to
      participants in Health Councils (answering rate = 65.4%); c) Health workers (N =
      45), by Delphi Process (answering rate = 58.5%). RESULTS: The people consider
      pains in their joints and allergies as the priority health problems, for the
      representatives of the community and the health workers the most important
      problems were dental hygiene and some chronic diseases. The needs detected as
      most important were, for the people from residential area, the lack of public
      gardens and cultural sites, for people from the inner city area it was the lack
      of public safety and in the rural area it was the lack of proper health
      resources. CONCLUSIONS: Although the different groups we study maintain a close
      agreement on what are the most important health problems and needs, we observed
      several interesting disagreement that could be explained by the different point
      of view that each group has on the process of health-disease, on perceiving
      problems and needs and on the sociodemographic differences among them.

PMID- 7713680
TI  - [The work climate among primary care workers].
AB  - The social organizational climate is a psychological variable which influences
      the behaviour of the people at work. With the aim of knowing and measuring the
      work environment in primary health care (Sector 11, Madrid), a transversal
      descriptive study has been performed on a sample of 350 people. We have used the
      survey WES (Work social environment scale), validated in Spain, which evaluates
      the dimensions: relationships, self-satisfaction and stability/change through 10
      subscales, in which a mark is obtained and profiles are created. We show the
      results of all the subscales and the analysed profiles according to professional
      establishments and assistance models (health centres and clinics). All the
      profiles show values over the average. The subscale which measures the
      organization shows the highest levels, and the one which measures pressure and
      control, the lowest. We conclude to value the organizational climate in primary
      health care as positive, with a relative homogeneity between establishments and
      centres. The knowledge of the behaviour and attitudes of the workers is basic
      when planning staff policy.

PMID- 7713681
TI  - [Proportional mortality studies: criteria for the selection of participant
      groups].
AB  - Proportional mortality designs are used widespread in occupational epidemiology.
      In this review those biases which can affect them, mainly the healthy worker
      bias, are discussed. Several options for their analysis and the assumptions to be
      accomplished for validity are reviewed: proportionate mortality analysis,
      standardized mortality ratio, and odds ratio. The inclusion of dead participants
      in a research exhibits several drawbacks. Starting out from the analysis of this
      sort of designs, the first criterium to select diseases is similar to case
      control studies: the reference group must not include diseases related with the
      exposure under study. Analyzing the relationship between mortality and incidence
      rates, criteria to select diseases to be investigated by proportional mortality
      studies are offered. These designs yield a valid inference when the disease is
      rare and irreversible. If the exposure shortens duration of disease, a toward-the
      null bias is introduced. The direction of bias is variable under other
      circumstances, although it shows a trend to be negative.

PMID- 7713682
TI  - [Spanish version of the epidemiologic dictionary of J. M. Last].
AB  - We comment briefly on the original edition of Last's dictionary of epidemiology
      and we make a detailed criticism of the translated version of the dictionary. We
      show several general problems of the spanish version and specifically discuss
      four epidemiology concepts (power, verosimility, child mortality and odds ratio)
      in which the definitions of the translated version are particularly confusing.

PMID- 7713683
TI  - [When is hospitalization adequate?].

PMID- 7713684
TI  - Seven resolutions to combat AIDS.

PMID- 7713685
TI  - Nursing management in the Nordic countries: a health system perspective.
AB  - Top-level nursing management by chief nurses is greatly needed to improve health
      services and their outcomes in all countries. But the question is: What knowledge
      and which skills are required for executive leadership and how important are
      each? The answers have come from over 150 chief nurses in five Nordic countries
      (Denmark, Finland, Iceland, Norway and Sweden) who responded to a mail survey
      and, in doing so, contributed to a better understanding of nursing management's
      function, main knowledge and skill requirements.

PMID- 7713686
TI  - Brokerage in multicultural nursing.
AB  - Nurses in contact with clients from different cultures often encounter beliefs at
      appear inconsistent with conventional Western medicine, resulting in the need for
      the nurse to act as a broker--i.e. translating and processing messages,
      instructions and belief systems from one group to a another.

PMID- 7713687
TI  - Health-related concerns of Canadian aboriginal people residing in urban areas.
AB  - Concerned about the health care system's inadequacy to meet the needs of
      Aboriginal Canadians, particularly of those in urban areas, the Canadian Nurses
      Association (CNA) initiated a project to determine their health-related concerns.
      The aim was to determine how the expressed needs of urban-dwelling Aboriginals
      could be met through a health care system based on primary health care.

PMID- 7713688
TI  - Effects of family disruption on Southeast Asian refugee women.
AB  - Identifying refugee women at a high risk of depression, anxiety and post
      traumatic stress is an important role of the nurse, so that appropriate
      interventions--including family and community support--can be implemented. Below,
      an assessment of Southeast Asian refugee women experiencing emotional distress
      from the disruption of family ties that occurred during war, escape and
      resettlement.

PMID- 7713689
TI  - HIV/AIDS risk high for nurses/midwives.

PMID- 7713690
TI  - The past, present and future of laparoscopic hernia repair.

PMID- 7713691
TI  - Laparoscopic extraperitoneal prosthetic inguinal hernia repair.

PMID- 7713692
TI  - Laparoscopic herniorrhaphy: a review of 401 tension-free repairs.

PMID- 7713693
TI  - Laparoscopic intraperitoneal hernioplasty.

PMID- 7713695
TI  - A modified technique of laparoscopic herniorrhaphy: operative approach and early
      results.

PMID- 7713696
TI  - The role of laparoscopy in abdominal trauma: a technique in search of an
      indication?

PMID- 7713697
TI  - Laparoscopy in the evaluation and management of abdominal trauma.

PMID- 7713694
TI  - Laparoscopic groin hernia repair.

PMID- 7713698
TI  - Gasless laparoscopy for complex surgical procedures.

PMID- 7713699
TI  - Minimal access surgery in children: the state of the art.

PMID- 7713701
TI  - Laparoscopic anti-reflux procedures and gastrostomy tubes in infants and
      children.

PMID- 7713700
TI  - Indications for laparoscopy in children.

PMID- 7713702
TI  - Laparoscopic splenectomy: present status and future outlook.

PMID- 7713703
TI  - Laparoscopic splenectomy: techniques and indications.

PMID- 7713704
TI  - Laparoscopic antireflux surgery.

PMID- 7713705
TI  - Laparoscopic technique of highly selective vagotomy.

PMID- 7713706
TI  - Laparoscopic highly selective vagotomy: definitive therapy for peptic ulcer
      disease.

PMID- 7713707
TI  - Three-dimensional laparoscopy in gastrointestinal surgery.

PMID- 7713708
TI  - Avoiding laparoscopic complications.

PMID- 7713709
TI  - Laparoscopic surgery: a technology in evolution.

PMID- 7713710
TI  - The changing world of rigid endoscopy.

PMID- 7713711
TI  - Stop considering the unbearable tedium of technology. Resident SCUT of the 1990s.

PMID- 7713712
TI  - Whither laparoscopy?

PMID- 7713713
TI  - "Extended" thymectomy, without sternotomy, performed by cervicotomy and
      thoracoscopic technique in the treatment of myasthenia gravis.

PMID- 7713714
TI  - Giant ventral hernias.

PMID- 7713715
TI  - Evaluation of Electroscope Electroshield System.
AB  - Hospitals have used a number of approaches to managing the risks of serious
      complications during laparoscopic monopolar electrosurgery: implementing
      clinician credentialing policies, considering the interaction of the primary
      equipment selected for laparoscopy, and introducing an accessory safety device-
      the Electroscope Electroshield System, which we evaluate here--to reduce the
      effects of high leakage currents originating on the shaft of the active
      electrode. We evaluated only the monopolar electrode shielding feature of the
      device.

PMID- 7713716
TI  - Guidance section: ensuring monopolar electrosurgical safety during laparoscopy.
AB  - In this study, we have discussed how direct leakage currents flowing through
      defects in active electrode insulation or capacitive leakage currents originating
      from the shaft of the active electrode can cause serious patient injuries during
      laparoscopic monopolar electrosurgical procedures. We have also discussed a
      number of other surgical scenarios, varying in likelihood, severity, and cause,
      in which electrosurgical injuries can occur during laparoscopy. This section
      provides a discussion of protective measures that hospitals can take to reduce
      the unique risks of serious patient injuries posed by monopolar electrosurgery
      used laparoscopically. In the Protective Measures for Laparoscopic Monopolar
      Electrosurgery table, we list our recommendations for reducing the risk of
      electrosurgical injuries in four common scenarios, as described in the Clinical
      and Technical Overview.

PMID- 7713717
TI  - Surgical video systems used in laparoscopy.
AB  - A significant amount of minimally invasive surgery (MIS) is now being performed
      using surgical video systems (SVSs), and with the increased application and sales
      of SVS equipment, many new SVS manufacturers and products have entered the
      medical device market. Consequently, the challenge of selecting an appropriate
      SVS has increased significantly, in part because of the complexity of the latest
      generation of equipment, which has evolved from solely optical endoscopes to
      mostly video electronics used with various types of endoscopes. When describing
      their products, manufacturers often present technical characteristics of their
      systems that can be complex and, many times, confusing. Although purchasers often
      rely on technical specifications when selecting an SVS, they actually need
      information that will illustrate the system's applicability in their clinical
      setting, which can be assessed only through clinical evaluation at the hospital.
      Also, the lack of standardized methods of specifying SVS performance and the
      difficulties in relating technical characteristics to clinical performance should
      diminish the emphasis that is often placed on specifications when selecting a
      system. In this article, we review and explain many common specifications of
      SVSs, focusing on their use with laparoscopes, and provide guidance on the
      limitations of each specification and the extent to which it may be useful. This
      information will help clinical engineers, biomedical technicians, and other
      readers participate in the technical aspects of selecting and managing an SVS for
      use with many types of endoscopes.

PMID- 7713718
TI  - Misconnection of bipolar electrosurgical electrodes.

PMID- 7713720
TI  - Air embolism and exsanguination from separation of two-piece side port/hemostasis
      valve cardiac catheter introducers.

PMID- 7713719
TI  - Cracked welds on EMI Therapies Systems/ATC Medical Technologies linear
      accelerators.

PMID- 7713722
TI  - Focus on laparoscopy.

PMID- 7713721
TI  - Malfunction of head-end drive mechanism of Hill-Rom Centra and Advance Series
      electric beds.

PMID- 7713723
TI  - Clinical and technical overview of monopolar electrosurgery during laparoscopy.

PMID- 7713724
TI  - Managing chronic congestive heart failure in the home.
AB  - Appropriate management of the patient with chronic congestive heart failure by
      the home health nurse is critical. Thorough assessment of the patient during the
      nursing visit can detect subtle changes in the patient's condition. Knowing what
      to look for and how to respond can improve the patient's quality of life
      significantly.

PMID- 7713725
TI  - Emerging clinical issues in home health psychiatric nursing.
AB  - Psychiatric nursing in the realm of home healthcare is relatively new, and there
      is a paucity of literature addressing the unique clinical concerns of the home
      health psychiatric nurse. This article explores clinical issues specific to
      psychiatric home health programs and offers a theory-based model for practice.

PMID- 7713726
TI  - Home health cardiac rehabilitation.
AB  - The Cardiac Rehabilitation Home Program provides the structural framework for
      patient access to cardiac recovery in the home setting. Using an
      interdisciplinary team approach, the program standardizes patient education,
      establishes a personalized activity program, and provides psychosocial support to
      the patient and family during the recovery process. The Cardiac Rehabilitation
      Home Program reduces the cost of delivering healthcare to the cardiac population
      while improving customer satisfaction, strategically positioning home health
      agencies for managed care contracts.

PMID- 7713727
TI  - Cluster care: an alternative to traditional care.
AB  - Studies of client satisfaction of the Traditional and Cluster Care service
      delivery models are virtually nonexistent. In an effort to provide healthcare
      services to Medicaid-eligible elderly home care clients, the New York City Human
      Resources Administration has implemented a new concept, Cluster Care. Because
      Cluster Care is probably going to be the wave of the 21st century, nurses need to
      be creative so that this new model will be more palatable to its recipients.

PMID- 7713728
TI  - Patient participation in changing behaviors.
AB  - Individuals who did not participate in an organized cardiac rehabilitation
      program were interviewed to discover how they made lifestyle changes after a
      cardiac illness. The themes obtained from the analysis of the interview data were
      consistent with the components of Barrett's nursing theory of power as knowing
      participation in change. Implications for professional nursing practice related
      to the themes are described.

PMID- 7713729
TI  - Training needs of home healthcare nurses.
AB  - To keep pace with the rapid expansion and increasing complexity of home
      healthcare, training needs of home healthcare nurses must be identified and
      subsequent training programs implemented. In this study, training needs of home
      healthcare nurses were identified and prioritized by comparing their ratings of
      important content areas of home healthcare nursing with ratings of their
      competence in each of these areas. High importance ratings matched with low
      competence ratings determined training needs. It is concluded that these
      identified needs form the basis for the development of training programs for the
      continued professional development of home healthcare nurses.

PMID- 7713730
TI  - Leadership.

PMID- 7713731
TI  - The camouflaged home health clinical nurse specialist.
AB  - Home health clinical nurse specialists are camouflaged. The contributions that
      they make to the home health specialty are stymied and often are invisible to
      individuals outside of the specialty. Their role is less developed and is less
      implemented than in other nursing specialties. There are impediments to role
      development, including difficulties in defining the clinical base of the
      specialty, the independence and consultative nature of all home health nursing
      practice despite differences in educational backgrounds or levels of practice,
      and regulatory and reimbursement restrictions. Responsibilities and
      qualifications of the home health clinical nurse specialist are presented. The
      author suggests that these nurses review and sign Medicare Plan of Treatment
      insurance forms (instead of physicians), because most of home healthcare is
      nursing care dealing with functional abilities rather than medical care.

PMID- 7713732
TI  - Using the calendar worksheet as one quality assessment tool.

PMID- 7713733
TI  - We can do that at home, but should we?

PMID- 7713734
TI  - Restorative nursing: home care's neglected resource.

PMID- 7713735
TI  - Wound assessment and documentation.

PMID- 7713737
TI  - Annie's story.

PMID- 7713736
TI  - The Lillian D. Wald Spirit of Nursing Award.

PMID- 7713738
TI  - Edie.

PMID- 7713739
TI  - Cardiac rehabilitation in the home: legal implications for the home healthcare
      nurse.

PMID- 7713740
TI  - Ask home healthcare nurses how they are incorporating nutrition screening
      assessment into their practice.

PMID- 7713741
TI  - Hb F-Macedonia-II [G gamma 104(G6)Lys-->Asn]: a new gamma chain variant.
AB  - In the course of our newborn screening program for the presence of
      hemoglobinopathies in the Republic of Macedonia, we have detected a new G gamma
      chain variant with a Lys-->Asn or AAG-->AAC substitution at codon 104. The
      variant was found in a blood sample from a healthy baby boy of Macedonian
      nationality. The abnormal chain was quantitated at 32.4% of the total gamma
      chains by reversed phase high performance liquid chromatography. The
      characterization of the variant was by sequence analysis of polymerase chain
      reaction-amplified DNA. The presence of the mutation in the mother was confirmed
      by Hph I restriction enzyme digestion of the polymerase chain reaction-amplified
      DNA fragment. Although the mutated G is the last nucleotide of exon 2 and part of
      the donor splice site sequence of the second intervening sequence of the G gamma
      gene, it appears that the splicing of the mRNA in this variant is not altered.

PMID- 7713742
TI  - Beta-thalassemia intermedia in a Lebanese child due to homozygosity for the -88
      (C-->T) mutation.
AB  - We report a case of beta-thalassemia intermedia involving a 3-year-old male child
      of Lebanese descent. Molecular studies of the family showed that he is homozygous
      for the -88 (C-->T) beta (+)-thalassemia mutation. This mutation is the second
      most common cause of beta-thalassemia in Black populations, and has also been
      reported in Asian Indians. A review of Lebanese beta-thalassemia cases revealed
      considerable mutation heterogeneity and excess homozygosity due to consanguinity.

PMID- 7713744
TI  - A rodent model for hemoglobin switching utilizing high performance liquid
      chromatography.
AB  - It has long been recognized that a treatment for beta hemoglobin chain anomalies
      could result if a way to reverse the Hb F to Hb A switch in humans were found.
      Studies of hemoglobin switching have been hampered by the fact that small animals
      normally used in the laboratory do not have a true Hb F. However, several small
      animal models which take advantage of a switch in minor beta chain proportions in
      certain strains of inbred mice and rats have been proposed and used. The use of
      these models has suffered from what, until now, could be considered technically
      demanding, time-consuming methodologies. In this study we report an effective,
      rapid and technically streamlined model of hemoglobin switching utilizing Fisher
      344 rats and high performance liquid chromatography with a weakly cationic
      column.

PMID- 7713743
TI  - Delta beta-thalassemia in an African-American: identification of the deletion
      endpoints and PCR-based diagnosis.
AB  - We describe an African-American child with beta-thalassemia intermedia. Molecular
      studies revealed that the proband is a compound heterozygote for the -29 (A-->G)
      beta (+)-thalassemia mutation and an extensive deletion involving the delta- and
      beta-globin genes. The proband's mother is a simple carrier of the deletion and
      exhibits the phenotype of delta beta-thalassemia rather than hereditary
      persistence of fetal hemoglobin. The deletion spans 11,767 bp, with the 5'
      deletion endpoint located 2,455 bp upstream of the delta-globin gene mRNA Cap
      site and the 3' endpoint located 441 bp downstream of the termination codon of
      the beta-globin gene. Based on this information, we have developed a polymerase
      chain reaction strategy for the rapid detection of this delta beta-thalassemia
      deletion.

PMID- 7713745
TI  - Interactions at the alpha 1 beta 1 interface in hemoglobin: a single amino acid
      change affects dimer ratio in transgenic mice expressing human hemoglobin.
AB  - The erythrocytes of transgenic mice expressing human hemoglobin contain mouse,
      human, and two hybrid hemoglobins. These hybrids include a predominant one, the
      human-alpha/mouse-beta and one found at lower levels, the human-beta/mouse-alpha.
      We used molecular modeling-aided hydropathic analysis of the globin alpha 1 beta
      1 interface to identify a residue partly or wholly responsible for this
      distribution. Hemoglobin containing a single amino acid change [beta 112(G14)Cys-
      >Val] was expressed in transgenic mice. The hybrid ratio was reversed in
      transgenic mice expressing this mutated human hemoglobin as compared to the
      control transgenic mice expressing native human hemoglobin. These results
      demonstrate the importance of subunit assembly in the expression of hybrids in
      transgenic animals and may lead to successful design approaches for optimal
      expression of hemoglobin in larger animals such as the pig.

PMID- 7713746
TI  - Two new alpha chain variants found during glycated hemoglobin screening: Hb
      Tatras [alpha 7(A5)Lys-->Asn] and HB Lisbon [alpha 23(B4)Glu-->Asp].

PMID- 7713747
TI  - A case of HB J-Meerut (or Hb J-Birmingham) [alpha 120(H3)Ala-->Glu].

PMID- 7713748
TI  - Hb A2-Sant' Antioco [alpha 2 delta (2)93(F9)Cys-->Gly]: a new delta chain variant
      identified by sequencing of amplified DNA.

PMID- 7713749
TI  - De novo beta-globin gene mutation [beta 63(E7)His-->Tyr] giving rise to Hb M
      disease in a Newfoundlander.

PMID- 7713750
TI  - A new alpha alpha alpha anti-3.7 alpha-globin allele.

PMID- 7713751
TI  - Beta-thalassemia in Iran: a high incidence of the nonsense codon 39 mutation on
      the island of Queshm.

PMID- 7713752
TI  - In situ hybridization comes of age.

PMID- 7713754
TI  - Study of numerical aberrations of chromosome 1 by fluorescent in situ
      hybridization and DNA content by densitometric analysis on (pre)-malignant
      cervical lesions.
AB  - In an attempt to determine whether the fluorescent in situ hybridization (FISH)
      can be used as a rapid approach for the identification of aneuploidy in
      premalignant cervical smears, a centromeric probe for chromosome 1 was used. The
      results from the FISH experiments were compared with measurements of the overall
      DNA content obtained by means of an image analysis system. With progression to
      neoplasia, a decrease of the frequency of cells with two spots was observed, due
      to an increasing polysomy of chromosome 1. As far as the DNA content was
      concerned, an increasing DNA index and 5C-exceeding ratio (fraction of cells with
      a DNA content higher than 5C) was observed. Classification of the FISH results by
      a linear discriminant analysis revealed that 67.6% of the cases were classified
      in agreement with the CIN classification. These data suggest that chromosome 1
      may be considered as a marker chromosome for pre-malignant cervical lesions and
      that the DNA content measurements are complementary to the FISH results.

PMID- 7713753
TI  - Combined analysis of in situ hybridization, cell cycle and structural markers
      using reflectance and immunofluorescence confocal microscopy.
AB  - A method for the simultaneous detection of mRNA by reflectance in situ
      hybridization (RISH), cell cycle and structural markers by immunofluorescence
      using confocal laser scanning microscopy is presented. The mRNA expression of two
      ras-related genes rhoB and rhoC was analysed in human breast cancer cell lines
      and human histological specimens (breast cancer tissues and skin biopsies). In
      breast cancer cell lines, the conditions were optimized to detect RNA-RNA hybrids
      and DNA synthesis after pulse-labelling with bromodeoxyuridine. Endonuclease
      exonuclease digestion, which allows the accessibility to specific antibodies of
      halogenated pyrimidine molecules, was carried out following ISH. Finally,
      cytokeratin or vimentin staining was performed. The detection of signals, arising
      from 1-nm colloidal gold particles without silver enhancement, by reflectance
      confocal laser scanning microscopy is described. Bromodeoxybiridine DNA markers
      and cytokeratin/vimentin staining were detected concomitantly using different
      fluorochromes. To allow comparative expression of two related genes, the mRNA of
      rhoB and rhoC were detected using digoxigenin- or biotin-labelled riboprobes and,
      after 3-D imaging, a detailed analysis by optical horizontal (x, y) and vertical
      (x, z) sectioning was undertaken. The subsequent bromodeoxyuridine detection
      procedure permitted to us explore the specific transcription of these two genes
      during S and non-S phases. This method allows the identification and localization
      of several subcellular components in cells within a complex tissue structure and
      makes it possible to analyse further transcript localization in relation to the
      function of the encoded protein and to the cell cycle.

PMID- 7713755
TI  - CCD microscopy and image analysis of cells and chromosomes stained by
      fluorescence in situ hybridization.
AB  - This paper reviews methods and applications of CCD microscopy for analysing cells
      and chromosomes subjected to fluorescence in situ hybridization (FISH). The
      current status of indirect and direct FISH staining methods with respect to probe
      labelling, detection sensitivity, multiplicity and DNA resolution is summarized.
      Microscope hardware, including special multi-band pass filters and CCD cameras
      required for FISH analysis, is described. Then follows a detailed discussion of
      current and emerging applications such as the automated enumeration of
      chromosomal abnormalities (counting of dots in interphase cells), comparative
      genomic hybridization, automated evaluation of radiation-induced chromosomal
      translocations, and high-resolution DNA mapping on highly extended chromatin.
      Finally, the limitations of the present methodology and future prospects are
      discussed.

PMID- 7713756
TI  - Combined immunocytochemistry and non-isotopic in situ hybridization for the
      ultrastructural investigation of human parvovirus B19 infection.
AB  - Parvovirus B19 is a single-stranded DNA virus with a specific tropism for human
      erythroid precursor cells. The virus codes for two overlapping structural
      (capsid) proteins and one non-structural protein which is thought to perform
      essential functions in viral replication, transcription and packaging. The
      ultrastructural localization of these proteins was achieved in cultured
      haemopoietic cells derived from fetal liver which had been infected in vitro and
      subsequently embedded in LR White acrylic resin. Postembedding immunogold
      detection of B19 structural and non-structural proteins was combined with
      localization of viral nucleic acid by in situ hybridization using a digoxigenin
      labelled probe and different sized gold labels. The majority of the B19 capsid
      protein and DNA present in cells harvested 48 hours post-infection co-localized
      within the centri-nuclear region of erythroid cells demonstrating characteristic
      chromatin margination. Relatively little DNA hybridization signal was present
      over paracrystalline inclusions strongly labelled with anti-capsid protein
      monoclonal antibody R92F6. Viral DNA and capsid protein were co-localized in
      apparent egress from the nucleus through nuclear pores. B19 non-structural
      protein was detected in association with both nuclear and cytoplasmic arrays of
      capsids, supporting the view that this protein plays an important role in viral
      packaging and remains associated with the complete viral particle until its
      release from the cell. Co-localization of viral nucleic acid and proteins at the
      ultrastructural level is a flexible, rapid and highly specific tool for
      examination of viral life-cycles within cells.

PMID- 7713757
TI  - Detection of human papillomavirus in cervical scrapings by in situ hybridization
      and the polymerase chain reaction in relation to cytology.
AB  - A gynaecological out-patient population consisting of 200 patients aged 19-43
      years (mean age 34.2 years) was screened for the presence of human papillomavirus
      (HPV) by the polymerase chain reaction and in situ hybridization on cervical
      scrapings. A novel method was applied for the detection of HPV in cervical cells
      by embedding them in a paraffin block before in situ hybridization was performed.
      This technique resulted in well preserved cytological morphology, easy
      performance and economy of probes. In eight of the 200 patients (4%), human
      papillomavirus DNA was revealed by the polymerase chain reaction. Subtyping
      revealed the presence of HPV serotype 16 DNA in three of these patients. In one
      patient HPV serotype 18 DNA was also present. The in situ hybridization assay was
      able to detect all those cases with a specific HPV serotype infection.

PMID- 7713758
TI  - Improved detection of DNA aneuploidy in primary breast cancer using quantitative
      DNA image analysis in combination with fluorescent in situ hybridization
      technique.
AB  - To obtain more information about the relationship between numerical aberrations
      of chromosome 1 and the overall DNA content of breast cancer cells, fluorescent
      in situ hybridization with a pericentromeric probe for this chromosome and image
      analysis based densitometry were carried out on imprints of benign (15 cases,
      mainly fibroadenomas) and malignant breast disease (31 invasive ductal carcinomas
      out of 45 cases). The most pronounced aneuploidy was observed in invasive ductal
      and lobular carcinoma cases both by in situ hybridization and DNA content (76.7
      and 75.0% were aneuploid). The frequency of cells with two spots for chromosome 1
      was 48.3 and 51.5%, respectively, as compared to 80.3% in control lymphocytes.
      There was a weak overall correlation (r2 = 0.83) between DNA content and copy
      number of chromosome 1 in the malignant samples, although some of the DNA
      diploid/near diploid carcinomas showed a marked aneusomy for this chromosome.
      Also, some aberrations were present in the benign breast disease samples.
      Classification of cases by a linear discriminant analysis was most accurate when
      both techniques were combined (77% of cases correctly classified, according to
      anatomo-pathological diagnosis). The variables which received the highest weight
      in the linear discriminant function are the percentage DNA-diploid cells and the
      fraction of cells with two spots for chromosome 1. The sensitivity and sources of
      error of both techniques is considered.

PMID- 7713759
TI  - Evaluation of novel formulations of 35S- and 33P-labelled nucleotides for in situ
      hybridization.
AB  - Radioactive in situ hybridization predominantly utilizes either RNA probes or
      oligonucleotide probes. The properties of various formulations of [35S]UTP alpha
      S have been studied with respect to probe labelling and when applied to in situ
      hybridization. A new formulation has been prepared that combines a high physical
      concentration with a high specific activity so that, theoretically, predominantly
      full-length, high-specific-activity primary transcripts are produced. [alpha
      33P]UTP can also be used for in situ hybridization and it compares favourably to
      35S-labelled probes in terms of resolution and sensitivity. Both radiolabels can
      also be used to label oligonucleotide probes by a tailing reaction. [35S]dATP
      alpha S has been reformulated specifically for labelling oligonucleotides. The
      traditional stabilizer, dithiothreitol, which may cause precipitation within the
      tailing reaction buffer, has been replaced with an alternative stabilizer that
      avoids this problem while maintaining the stability of the nucleotide.

PMID- 7713760
TI  - Fluorescein as a label for non-radioactive in situ hybridization.
AB  - Non-radioactive techniques can be applied to many in situ hybridization (ISH)
      applications, and a number of non-radioactive labels for this process have been
      reported. However, these labels have some inherent problems in terms of both
      background and signal-to-noise values. We have sought to address these issues by
      searching for an alternative label that has the following features: efficient
      incorporation into probes, non-endogenous to biological systems, the availability
      of a high-affinity, high-specificity antibody. Fluorescein has been shown to meet
      these requirements. In addition, due to the fluorescent nature of the label, it
      has been possible to design a rapid, non-radioactive labelling assay and also to
      view in situ hybridization results by direct fluorescence in certain ISH
      applications. The hybridization kinetics have been investigated. Significant
      improvements have been made to the hybridization buffer leading to reduced
      background and increased rates of hybridization when compared to traditional
      hybridization buffers.

PMID- 7713762
TI  - [Fatal outcome after retrograde insufflation of the eustachian tube].
AB  - This case report describes a lethal complication of retrograde air insufflation
      through the Eustachian tube after myringotomy. A 35-year-old woman presented with
      otalgia and hearing loss in her left ear, which had occurred after an upper
      respiratory infection. Otoscopy showed a middle ear effusion. A myringotomy was
      performed under mask anesthesia in a private clinic. During subsequent retrograde
      Eustachian tube insufflation, the patient experienced sudden convulsions,
      followed by cardiac and respiratory arrest. The patient then died some hours
      later from generalized cardiac and circulation break-down in the intensive care
      unit of a nearby hospital. The cause of the cardiac and circulation collapse
      could not be defined completely, but it is believed than an anatomical variant of
      the tegmen tympani was responsible for the tragic outcome because of an air
      embolus.

PMID- 7713763
TI  - [Plasmacytoma of the ENT region. Diagnosis and therapy].

PMID- 7713764
TI  - [Hormonal effects on regulation of electrolytes and volumes in the inner ear].

PMID- 7713765
TI  - [Pathological changes in the middle ear and delayed speech development.
      Preventable sequelae of disordered tube function and seromucotympanum].
AB  - Serous otitis media is a frequent disorder, as 80-90% of children up to the age
      of 8 years experience at least one episode of middle ear effusion. When deciding
      on a therapeutic strategy, it should be taken into consideration that there is a
      spontaneous recovery rate of about 95%. Initially, conservative treatment should
      be given (Valsalva maneuver), as the efficacy of drug therapy is questionable. In
      our opinion, in cases of persistent middle ear effusion an adenoidectomy plus
      myringotomy should be performed. In cases of recurrence, a ventilation tube
      should be inserted to reduce eardrum pathology as well as delayed speech and
      mental development.

PMID- 7713761
TI  - [Does malignant lateral cervical cyst still exist?].
AB  - A case of a carcinoma-in-situ developing in a lateral cervical cyst
      (branchiogenic carcinoma) is described and compared with metastatic cervical
      lymph nodes (due to cancers from unknown primary sites). The authors are
      convinced that branchial carcinomas do exist, but are extremely rare. The
      available literature is reviewed.

PMID- 7713766
TI  - [Preliminary results of a prospective randomized study of primary chemotherapy in
      carcinoma of the oral cavity and pharynx].
AB  - Although induction chemotherapie given prior to local therapy produces
      encouraging initial response rates in head and neck cancer, randomized studies
      have failed to demonstrate an advantage in survival. All randomized studies have
      included only patients with far advanced stage III and IV disease. To us this is
      the main reason for the low rate of complete responses demonstrated (maximum,
      18%). Frei et al. estimate that 40-50% complete responders are necessary before
      improved survival benefit will occur. To date, such complete response rates with
      induction chemotherapy are only attainable in resectable T2-T3, N0-N2 disease.
      Therefore, we started a prospective randomized trial that included only patients
      with earlier disease. Patients were randomized to receive either induction
      chemotherapy with 3 cycles of carboplatin/5-fluorouracil prior to surgery and
      radiotherapy (arm A, 49 patients) or standard treatment with surgery and
      radiotherapy (arm B, 48 patients). Patients were stratified by primary tumor site
      and neck disease. After a follow-up of 12-48 months, overall survival was 72% in
      arm A and 53% in arm B, but this difference was not significant. Considering only
      the results in patients with cancer of the oral cavity and tonsils, overall
      survival was 87% in arm A and 45% in arm B (p < 0.04). At present, the numbers of
      patients with cancers of the tongue base and hypopharynx are too small for a
      statistically significant statement. However, preliminary data indicate a better
      overall and disease-free survival without chemotherapy in these patients.
      Therefore, we now recommend induction chemotherapy in all patients with stage T2
      T3 and N0-N2 carcinomas of the oral cavity and tonsils prior to surgery but not
      in patients with cancers of the hypopharynx and base of tongue.

PMID- 7713767
TI  - [Stapedectomy in congenital stapes fixation].
AB  - Because several cases of cerebral-spinal fluid leakage (perilymph gushers) have
      been reported during stapedectomy for congenitally fixed stapes in children, many
      otologists advise against surgical intervention. The pathophysiologic mechanism
      of the gusher and its association with a congenitally fixed stapes is, however,
      poorly understood. This study was designed to examine the pre-operative
      presentation and hearing results of 10 children undergoing stapedectomies for
      congenital fixation. No perilymph gushers of significant sensorineural hearing
      loss was encountered. All but one case resulted in closure of the air-bone gap
      and speech frequencies to within 20 dB. The average air-bone gap was 11.2 dB.
      Minor congenital abnormalities of the stapes suprastructure were seen in 3 cases.
      Review of case reports in the literature indicate that gushers in association
      with surgical manipulation of the congenitally-fixed stapes occur almost
      exclusively in males and that pathophysiology involves a defect in the internal
      auditory canal (as opposed to a patent cochlear aqueduct). A pre-existing
      sensorineural hearing loss may also be a risk factor for perilymph gusher.

PMID- 7713769
TI  - [Multiplanar angulated 2D reconstruction. A new CT technique for imaging the
      facial nerve canal].
AB  - For imaging the facial canal in its tympanic and mastoid segments, a new
      technique was developed with high-resolution computed tomography (HRCT). This
      method is based on comparative anatomical studies and makes it possible to depict
      the course of the facial canal, especially in malformations of the middle ear and
      in cases of fractures, tumors and cholesteatomas. A longitudinal scan of the
      petrous part of the temporal bone is obtained by reconstruction based on primary
      axial CT-standards. In these longitudinal scans the facial canal is shown both in
      its tympanic and mastoidal segment. For longitudinal reconstruction the scan is
      orientated through the anterior margin of the carotid canal and petrous pyramid.
      For evaluating the facial canal in this study, the lateral semicircular canal and
      stylomastoid foramen are sure landmarks. The sensitivity for evaluating the
      tympanic segment of the facial canal is 100%. This new technique should be
      applied in cases in which the exact course of the facial canal must be known
      preoperatively.

PMID- 7713768
TI  - [Peak flow measurement in patients with laryngeal and tracheal stenoses. A simple
      and valuable spirometric method].
AB  - Body plethysmographic and spirometric indices can be used for routine
      examinations of obstructive lesions of the larynx and upper trachea. Total
      resistance, forced expiratory volume in 1 sec (FEV1) and the S-shaped flow
      pressure loop can show clinically significant extrathoracic stenoses. We have now
      also measured peak inspiratory flow (PIF) and peak expiratory flow (PEF) with a
      peak flow meter. Easy handling was compared with good reliability of the
      measurements and possible detection of laryngeal lesions. Extrathoracic stenoses
      caused turbulent flow, with a flow-dependent increase in total resistance (Rtot).
      This resistance increased only with severe stenoses, while mild stenoses were
      often not detected. Peak expiratory flow reacted earlier than did peak
      inspiratory flow and seemed to be the most reliable parameter for detecting an
      extrathoracic stenosis. Testing was easy to perform and was usually reproducible.
      Patients with additional peripheral obstructive stenoses required a more specific
      examination.

PMID- 7713770
TI  - [Epithelialization of porous biomaterials with isolated respiratory epithelial
      cells in vivo].
AB  - Extensive tracheal defects after prolonged assisted ventilation, trauma or large
      resections in tumor surgery are a challenge in plastic and reconstructive
      surgery. Defects which cannot be satisfactorily repaired reguine near of an
      alloplastic tracheal replacement. Previous experimental and clinical experiences
      in the development of an alloplastic tracheal prosthesis have demonstrated that
      the main cause for failure is the lack of an epithelial lining of luminal
      surfaces and inadequate biophysical properties of the prosthesis. With the use of
      a cell-seeding technique tested in vitro on biomaterials epithelialization of
      tracheal prostheses can be tested in vivo. In animal experiments isolated
      respiratory cells were seeded into implanted tubular prostheses of porous
      polyurethane or expanded polytetrafluorethylene. Light and scanning microscopic
      investigations then showed the tendency of epithelialization to occur on the
      luminal surfaces. Vigorous squamous epithelium cell layers that were single and
      (predominantly) multiple layers were found. Differentiated cilated or mucous
      cells were not detected in any case. The present results have shown that
      epithelialization of incorporated porous implants is possible. The realization of
      usable tracheal replacement for clinical practice must still be tested in further
      experiments.

PMID- 7713772
TI  - [Effect of linguistic competence on speech audiometry results using the Basel
      Sentence Test].
AB  - Linguistic competence, such as a mental lexicon knowledge of syntactic rules of
      the language and the use of semantic constraints, may impact central speech
      processing and play an important role in speech recognition. The influence of
      linguistic ability on speech understanding was investigated using the Basel
      Sentence Understanding Test. The subject's linguistic ability was determined
      based upon educational background (elementary school, high school and or
      university) and intelligence quotients (IQ) based on the reduced version of the
      Hamburg-Wechsler Intelligence Test. Forty normally-hearing subjects listened to
      five test forms of the Basel Sentence Understanding Test. Each test form
      comprised a fraction of 15 low-predictable (LP) test items and 15 high
      predictable (HP) test items based on the amount of contextual information in the
      phrases. No effect of educational background and IQ-value could be demonstrated
      on the scores of LP sentences. However, there was a small but significant
      influence of educational background and IQ-value on the scores of HP sentences.
      The implications of these findings on clinical speech audiometry are discussed.

PMID- 7713771
TI  - [Comparison of methods for early detection of noise vulnerability of the inner
      ear. Amplitude reduction of otoacoustic emissions are most sensitive at
      submaximal noise impulse exposure].
AB  - Noise-induced temporary impairment of cochlear function was measured with several
      audiometric tests in order to evaluate which method best predicts a vulnerable
      cochlea. We tested 10 normally-hearing and 13 subjects who were positive for
      temporary threshold shifts (TTS). The latter were selected from 194 soldiers who
      demonstrated a TTS higher than 15 dB after regular training with firearms.
      Acoustic distortion products (DPOAE), click-evoked otoacoustic emissions (TEOAE),
      upper limit of hearing (ULH) and pure-tone and high-frequency audiometry were
      used to evaluate possible increased vulnerability of the cochlea. Tests were
      conducted at lower sound intensities (white noise, 90 dB SPL, 5 min; impact
      noise, 100 or 106 dB SPLs, 10 impulses/s, 5 min). Seventy per cent of the TTS
      positive soldiers studied exhibited significant reductions of TEOAE amplitudes,
      whereas a stable emission was observed in all control subjects. DPOAE alterations
      were seen in 38% of the soldiers tested. These results indicate that TEOAE is the
      most sensitive, objective method for detecting a positive disturbance in cochlear
      function. Although the upper limit of hearing was also a very sensitive method,
      variability of this psychoacoustic method depended on the help and experience of
      the subjects being tested.

PMID- 7713773
TI  - Late Effects of Normal Tissues Consensus Conference. San Francisco, California,
      August 26-28, 1992.

PMID- 7713774
TI  - RTOG Late Effects Working Group. Overview. Late Effects of Normal Tissues (LENT)
      scoring system.

PMID- 7713775
TI  - EORTC Late Effects Working Group. Late Effects toxicity scoring: the SOMA scale.

PMID- 7713776
TI  - LENT SOMA scales for all anatomic sites.

PMID- 7713777
TI  - Chronic neuroendocrinological sequelae of radiation therapy.
AB  - A variety of neuroendocrine disturbances are observed following treatment with
      external radiation therapy when the hypothalamic-pituitary axis (HPA) is included
      in the treatment field. Radiation-induced abnormalities are generally dose
      dependent and may develop many years after irradiation. Growth hormone deficiency
      and premature sexual development can occur following doses as low as 18 Gy
      fractionated radiation and are the most common neuroendocrine problems noted in
      children. Deficiency of gonadotropins, thyroid stimulating hormone, and
      adrenocorticotropin are seen primarily in individuals treated with > 40 Gy HPA
      irradiation. Hyperprolactinemia can be seen following high-dose radiotherapy (>
      40 Gy), especially among young women. Most neuroendocrine disturbances that
      develop as a result of HPA irradiation are treatable; patients at risk require
      long-term endocrine follow-up.

PMID- 7713778
TI  - Late effects of radiation on the eye and ocular adnexa.
AB  - A clinically useful classification system is suggested that can be used in
      prospective trials to evaluate the effects of radiation on the visual system. We
      review radiation-induced pathophysiological and clinical changes of the various
      ocular structures as well as dose-response data and management of ocular
      complications. The rationale for the classification scheme chosen is also
      discussed.

PMID- 7713779
TI  - Late effects of radiation therapy in the head and neck region.
AB  - The head and neck region is composed of numerous structures, each with an
      inherent response to radiation that is largely governed by the presence or
      absence of mucosa, salivary glands, or specialized organs within that site.
      Irradiated mucocutaneous tissues demonstrate increased vascular permeability that
      leads to fibrin deposition, subsequent collagen formation, and eventual fibrosis.
      Irradiated salivary tissue degenerates after relatively small doses, leading to
      markedly diminished salivary output. This, in turn, effects the teeth by
      promoting dental decay which, in turn, effects the integrity of the mandible.
      Details of these changes are presented, including their pathophysiology, clinical
      syndromes, and potential treatment.

PMID- 7713780
TI  - Thyroid abnormalities after therapeutic external radiation.
AB  - The thyroid gland is the largest pure endocrine gland in the body and one of the
      organs most likely to produce clinically significant abnormalities after
      therapeutic external radiation. Radiation doses to the thyroid that exceed
      approximately 26 Gy frequently produce hypothyroidism, which may be clinically
      overt or subclinical, as manifested by increased serum thyrotropin and normal
      serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may
      arise when the pituitary region receives doses exceeding 50 Gy with conventional,
      1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk
      of Graves' disease or euthyroid Graves' ophthalmopathy. Silent thyroiditis,
      cystic degeneration, benign adenoma, and thyroid cancer have been observed after
      therapeutically relevant doses of external radiation. Direct or incidental
      thyroid irradiation increases the risk for well-differentiated, papillary, and
      follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest
      following radiation at a young age, decreases with increasing age at treatment,
      and increases with follow-up duration. The potentially prolonged latent period
      between radiation exposure and the development of thyroid dysfunction, thyroid
      nodularity, and thyroid cancer means that individuals who have received neck or
      pituitary irradiation require careful, periodic clinical and laboratory
      evaluation to avoid excess morbidity.

PMID- 7713781
TI  - Pathophysiology of irradiated skin and breast.
AB  - The evolution, time course, and dose response of gross and histologic changes
      associated with the acute and late changes of the skin are noted and a composite
      pathophysiologic operational model given. This model focuses the selection of the
      observations to be "scored" to assess the tolerance and cosmetic response of the
      skin and breast to different dose and combined therapy studies. Skin scoring,
      Late effects skin, Late effects breast, Skin irradiation response, Breast
      radiation response, Pathophysiology of irradiated skin, Dose tolerance of skin,
      Dose tolerance of breast, Skin functional unit, Microvessel response to
      irradiation.

PMID- 7713782
TI  - Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints,
      and potential scoring systems.
AB  - Toxicity of the respiratory system is a common side effect and complication of
      anticancer therapy that can result in significant morbidity. The range of
      respiratory compromise can extend from acute lethal events to degrees of chronic
      pulmonary decompensation, manifesting years after the initial cancer therapy.
      This review examines the anatomic-histologic background of the lung and the
      normal functional anatomic unit. The pathophysiology of radiation and
      chemotherapy induced lung injury is discussed as well as the associated clinical
      syndromes. Radiation tolerance doses and volumes are assessed in addition to
      chemotherapy tolerance and risk factors and radiation-chemotherapy interactions.
      There are a variety of measurable endpoints for detection and screening. Because
      of the wide range of available quantitative tests, it would seem that the
      measurement of impaired lung function is possible. The development of staging
      systems for acute and late toxicity is discussed and a new staging system for
      Late Effects in Normal Tissues (LENT) is proposed.

PMID- 7713783
TI  - Radiation injury to the heart.
AB  - For the RTOG Consensus Conference on Late Effects of Cancer Treatment we
      summarize the clinical manifestations of cardiac complications appearing months
      to years following incidental irradiation of the heart during treatment of
      thoracic neoplasms. The most common effects present as pericardial disease,
      however, it is becoming more clear that precocious or accelerated coronary artery
      disease is an important late effect, especially in patients treated with
      radiation before the age of 21 years. To the extent it is known, the
      pathophysiology of the various syndromes is described and the extensive
      literature on dose, volume, and fractionation factors is reviewed. Based upon our
      current understanding of late cardiac effects, a clinical grading system has been
      developed and is published elsewhere in this issue.

PMID- 7713784
TI  - Late effects of radiation therapy on the gastrointestinal tract.
AB  - Late gastrointestinal complications of radiation therapy have been recognized but
      not extensively studied. In this paper, the late effects of radiation on three
      gastrointestinal sites, the esophagus, the stomach, and the bowel, are described.
      Esophageal dysmotility and benign stricture following esophageal irradiation are
      predominantly a result of damage to the esophageal wall, although mucosal
      ulcerations also may persist following high-dose radiation. The major late
      morbidity following gastric irradiation is gastric ulceration caused by mucosal
      destruction. Late radiation injury to the bowel, which may result in bleeding,
      frequency, fistula formation, and, particularly in small bowel, obstruction, is
      caused by damage to the entire thickness of the bowel wall, and predisposing
      factors have been identified. For each site a description of the pathogenesis,
      clinical findings, and present management is offered. Simple and reproducible
      endpoint scales for late toxicity measurement were developed and are presented
      for each of the three gastrointestinal organs. Factors important in analyzing
      late complications and future considerations in evaluation and management of
      radiation-related gastrointestinal injury are discussed.

PMID- 7713785
TI  - Hepatic toxicity resulting from cancer treatment.
AB  - Radiation-induced liver disease (RILD), often called radiation hepatitis, is a
      syndrome characterized by the development of anicteric ascites approximately 2
      weeks to 4 months after hepatic irradiation. There has been a renewed interest in
      hepatic irradiation because of two significant advances in cancer treatment:
      three dimensional radiation therapy treatment planning and bone marrow
      transplantation using total body irradiation. RILD resulting from liver radiation
      can usually be distinguished clinically from that resulting from the preparative
      regime associated with bone marrow transplantation. However, both syndromes
      demonstrate the same pathological lesion: veno-occlusive disease. Recent evidence
      suggests that elevated transforming growth factor beta levels may play a role in
      the development of veno-occlusive disease. Three dimensional treatment planning
      offers the potential to determine the radiation dose and volume dependence of
      RILD, permitting the safe delivery of high doses of radiation to parts of the
      liver. The chief therapy for RILD is diuretics, although some advocate steroids
      for severe cases. The characteristics of RILD permit the development of a grading
      system modeled after the NCI Acute Common Toxicity Criteria, which incorporates
      standard criteria of hepatic dysfunction.

PMID- 7713786
TI  - Clinical radiation nephropathy.
AB  - An analysis of the normal tissue effects of irradiation of the kidney is
      presented. Various clinical syndromes resulting from treatment are described as
      well as the potential cellular basis for these findings. Effects of concurrent
      and/or sequential treatment with irradiation and various chemotherapeutic agents
      are discussed and the impact of these agents on toxicity presented. Adverse
      consequences of renal treatment in the child is described and possible radiation
      effects on so-called compensatory hypertrophy following nephrectomy presented.
      Renal consequences described to date of bone marrow transplantation programs
      utilizing irradiation are also presented. The necessity of a dose-volume
      histogram analysis approach to analyzing renal toxic effects in patients followed
      for long (> 10 year) periods is essential in developing accurate guidelines of
      renal tolerance.

PMID- 7713787
TI  - The response of the urinary bladder, urethra, and ureter to radiation and
      chemotherapy.
AB  - A comprehensive review of the physiological and clinical response of the urinary
      bladder, ureter, and urethra to radiation and chemotherapy is presented. The
      clinical syndromes that follow therapy for cancer of the bladder, prostate, and
      cervix are reviewed in detail. Methods of assessing, scoring, and managing
      toxicity are discussed.

PMID- 7713788
TI  - Late injury of cancer therapy on the female reproductive tract.
AB  - The purpose of this article is to review the late effects of cancer therapy on
      the female reproductive tract. The anatomic sites detailed are the vulva, vagina,
      cervix, uterus, fallopian tubes, and ovaries. The available pathophysiology is
      discussed. Clinical syndromes are presented. Tolerance doses of irradiation for
      late effects are rarely presented in the literature and are reviewed where
      available. Management strategies for surgical, radiotherapeutic, and
      chemotherapeutic late effects are discussed. Endpoints for evaluation of
      therapeutic late effects have been formulated utilizing the symptoms, objective,
      management, and analytic (SOMA) format. Late effects on the female reproductive
      tract from cancer therapy should be recognized and managed appropriately. A
      grading system for these effects is presented. Endpoints for late effects and
      tolls for the evaluation need to be further developed.

PMID- 7713789
TI  - Response of growing bone to irradiation: a proposed late effects scoring system.
AB  - The effect of radiation on epiphyseal bone growth is one of the most important
      dose-limiting factors in the radiotherapeutic management of children with
      malignant neoplasms. Clinical and laboratory evidence suggest that many factors
      may influence the severity of radiation-induced growth arrest. However, the
      absence of a consistent scoring system for late effects has hampered efforts to
      analyze the influence of various therapeutic maneuvers or to compare and collate
      results from different reported series. In this review, laboratory and clinical
      studies of radiation effects on growing bone are summarized, and a late effects
      scoring system is proposed.

PMID- 7713790
TI  - Late radiation injury to muscle and peripheral nerves.
AB  - Late radiation injury to muscles and peripheral nerves is infrequently observed.
      However, the success of radiation oncology has led to longer patient survival,
      providing a greater opportunity for late effects to develop, increase in severity
      and, possibly, impact the quality of life of the patient. In addition, when
      radiation therapy is combined with surgery and/or chemotherapy, the risk of late
      complications is likely to increase. It is clear that the incidence of
      complications involving muscles and nerves increases with time following
      radiation. The influence of volume has yet to be determined; however, an
      increased volume is likely to increase the risk of injury to muscles and nerves.
      Experimental and clinical studies have indicated that the alpha/beta ratio for
      muscle is approximately 4 Gy and, possibly, 2 Gy for peripheral nerve, indicating
      the great influence of fractionation on response of these tissues. This is of
      concern for intraoperative radiation therapy, and for high dose rate
      brachytherapy. This review of clinical and experimental data discusses the
      response of muscle and nerves late after radiation therapy. A grading system has
      been proposed and endpoints suggested.

PMID- 7713791
TI  - Hematopoietic stem cell compartment: acute and late effects of radiation therapy
      and chemotherapy.
AB  - The bone marrow is an important dose-limiting cell renewal tissue for
      chemotherapy, wide-field irradiation, and autologous bone marrow transplantation.
      Over the past 5-10 years a great deal has been discovered about the hematopoietic
      stem cell compartment. Although the toxicity associated with prolonged
      myelosuppression continues to limit the wider use of chemotherapy and
      irradiation, ways are being discovered to circumvent this toxicity such as with
      the increasing use of cytokines. This review describes what is known of how
      chemotherapy and irradiation damage stem cells and the microenvironment, how
      cytokines protect hematopoietic cells from radiation damage and speed marrow
      recovery after chemotherapy or marrow transplantation, and how various types of
      blood marrow cells contribute to engraftment and long-term hematopoiesis after
      high doses of cytotoxic agents and/or total body irradiation.

PMID- 7713793
TI  - LENT: a good beginning but...

PMID- 7713792
TI  - Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European
      Organization for Research and Treatment of Cancer (EORTC)

PMID- 7713794
TI  - The impact on quality of life by radiation late effects.
AB  - The Radiation Therapy Oncology Group (RTOG) is developing an improved scoring
      system for the late effects of radiation therapy. There is a need to assess the
      impact of treatment on long-term survival. The RTOG Late Effects Toxicity Grading
      Scale documents the absence or the degree to which a symptom or sign is present.
      The scale in itself does not, however, score the impact of symptoms on survival.
      This Late Effects Scale in conjunction with quality-of-life assessments will
      provide the information necessary to assess the impact of treatment toxicities on
      normal daily living. Neither documentation of late effects nor their impact on
      quality of survival is an end in itself. These scales are only instruments that
      should serve to direct us toward our higher goal of designing interventional
      studies concerned with the quality of survival or rehabilitation. The development
      of the Late Effects Toxicities Grading Scale is a beginning.

PMID- 7713795
TI  - Understanding radiation damage in late effect normal tissues: learning to
      negotiate the dose-volume-complication terrain or waiting for Godot?

PMID- 7713797
TI  - 7th International Scientific Meeting of the International Organization of
      Psychophysiology, (IOP). Macedonia, Greece, 27 September-2 October 1994.
      Abstracts.

PMID- 7713796
TI  - In Commemoration of the 12th anniversary of the International Organization of
      Psychophysiology.

PMID- 7713798
TI  - Excess oxygen delivery during muscle contractions in spontaneously hypertensive
      rats.
AB  - These experiments determined whether a deficit in oxygen supply relative to
      demand could account for the sustained decrease in tissue PO2 observed during
      contractions of the spinotrapezius muscle in spontaneously hypertensive rats
      (SHR). Relative changes in blood flow were determined from measurements of vessel
      diameter and red blood cell velocity. Venular hemoglobin oxygen saturation
      measurements were performed by using in vivo spectrophotometric techniques. The
      relative dilation [times control (xCT)] of arteriolar vessels during contractions
      was as large or greater in SHR than in normotensive rats (Wistar-Kyoto), as were
      the increases in blood flow (2 Hz, 3.50 +/- 0.69 vs. 3.00 +/- 1.05 xCT; 4 Hz,
      10.20 +/- 3.06 vs. 9.00 +/- 1.48 xCT; 8 Hz, 16.40 +/- 3.95 vs. 10.70 +/- 2.48
      xCT). Venular hemoglobin oxygen saturation was lower in the resting muscle of SHR
      than of Wistar-Kyoto rats (31.0 +/= 3.0 vs. 43.0 +/- 1.9%) but was higher in SHR
      after 4- and 8-Hz contractions (4 Hz, 52.0 +/- 4.8 vs. 43.0 +/- 3.6%; 8 Hz, 51.0
      +/- 4.6 vs. 41.0 +/- 3.6%). Therefore, an excess in oxygen delivery occurs
      relative to oxygen use during muscle contractions in SHR. The previous and
      current results can be reconciled by considering the possibility that oxygen
      exchange is limited in SHR by a decrease in anatomic or perfused capillary
      density, arteriovenular shunting of blood, or decreased transit time of red blood
      cells through exchange vessels.

PMID- 7713799
TI  - Role of reactive O2 in phagocyte-induced hypermetabolism and pulmonary injury.
AB  - Activated phagocytes possess an enormous capacity for O2 consumption via NADPH
      oxidase. NADPH oxidase partially reduces O2, forming superoxide (O2-). Host
      enzymes rapidly complete O2- reduction to H2O, leaving little trace of its prior
      existence. Our objectives were to estimate the magnitude of whole body phagocyte
      respiration and determine the contribution of NADPH-derived O2- to the ensuing
      phagocyte-induced pulmonary injury. These objectives were accomplished using
      specific inhibitors of NADPH oxidase, diphenyl iodonium (DPI) and di-2-thienyl
      iodonium (DTI). Guinea pigs received intravenous injections of DPI (3.5 mg/kg),
      DTI (7.5 mg/kg), or vehicle followed by phorbol myristate acetate (PMA).
      Phagocyte activation by PMA immediately increased whole body respiration from
      13.6 to 16.1 ml O2.kg-1.min-1 (P < 0.05). DPI and DTI completely blocked the
      increase in respiration induced by PMA injection (P < 0.05). Baseline respiration
      was unchanged by the NADPH oxidase inhibitor alone. Likewise, there was no effect
      on the respiration of isolated heart and kidney mitochondria from animals
      receiving the inhibitor with or without PMA. DPI attenuated the pulmonary injury
      induced by PMA. DPI attenuated the pulmonary injury induced by PMA. The ratio of
      lung water weight to dry weight was lower (6.4 +/- 0.3 vs. 8.3 +/- 0.6) and
      arterial PO2 was higher (86 +/- 9 vs. 56 +/- 6 Torr) in animals receiving DPI
      plus PMA than in those receiving PMA alone. In conclusion, phagocyte activation
      in vivo increased total body respiration by approximately 18%. The burst in
      respiration is attributed to the phagocyte respiratory burst in which NADPH
      oxidase partially O2 to O2-.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713800
TI  - Bronchomotor responses to hypoxia and hypercapnia in decerebrate cats.
AB  - Decerebrate animals are often used in investigations of the control of breathing
      because anesthesia-induced depression of respiratory reflexes is absent. We
      therefore investigated the level of tone and responsiveness of airway smooth
      muscle in seven decerebrate, paralyzed, and ventilated cats. Specifically, we
      measured the changes in pulmonary resistance (RL) and dynamic pulmonary
      compliance (CLdyn) in response to hypoxia and hypercapnia. All cats responded to
      hypoxia (approximately 10% O2 in N2) with significant increases (mean 49%, range
      5-156%) in RL from a mean control value of 0.0197 +/- 0.0081 (SD) cmH2O.ml-1.s.
      During inhalation of 5% CO2 in O2, RL increased significantly (mean 59%, range 16
      135%) from a mean control value of 0.0190 +/- 0.0056 cmH2O.ml-1.s. Decreases in
      CLdyn during hypoxia and hypercapnia were much smaller, averaging -9 and -11%,
      respectively. After atropine was administered, average control RL fell 50%, from
      0.0269 to 0.0134 cmH2O.ml-1.s (P < 0.05; n = 4). Hypoxic and hypercapnic gas
      mixtures did not affect pulmonary mechanics after atropine was administered. In
      three cats, oscillations of RL were synchronized to phrenic activity but only at
      low respiratory frequencies (approximately 12 cycles/min), indicating that airway
      smooth muscle responded slowly to vagal input. Pentobarbital sodium, like
      atropine, reduced control RL in three cats. These cats lost their
      bronchoconstrictor response to hypercapnia but had augmented responses to hypoxia
      compared with preanesthetic responses. We conclude that decerebrate cats possess
      resting bronchomotor tone and retain their responsiveness to hypoxia and
      hypercapnia. Thus the decerebrate cat is a useful model for studying the control
      of tracheobronchial smooth muscle.

PMID- 7713801
TI  - Dynamic exercise enhances regional cerebral artery mean flow velocity.
AB  - Dynamic exercise enhances regional cerebral artery mean flow velocity. J. Appl.
      Physiol. 78(1): 12-16, 1995.--Anterior (ACA) and middle (MCA) cerebral artery
      mean flow velocities (Vmean) and pulsatility indexes were determined using
      transcranial Doppler in 14 subjects during dynamic exercise after assessment of
      the carbon dioxide reactivity for both arteries. Right hand contractions provoked
      an elevation in left MCA Vmean [19% (12-28); P < 0.01], whereas the pulsatility
      decreased in all four arteries (P < 0.05). During right foot movement, left ACA
      Vmean increased by 23% (11-37; P < 0.01) with lesser (approximately 10%; P <
      0.05) increases in the other arteries, and pulsatility index decreased (P <
      0.05). During cycling, ACA and MCA Vmean increased bilaterally by 23% (10-49) and
      18% (5-32), respectively (P < 0.01), and the pulsatility was also elevated (P <
      0.05). Cerebral artery pulsatility did not demonstrate a focal response but
      depended did not demonstrate a focal response but depended on the muscle mass
      involved during exercise. The data demonstrate a significant increase in Vmean
      for the artery supplying the cortical projection of the exercising limb.
      Insignificant and marginally significant increases in Vmean may be related to
      sympathetically mediated vasoconstriction and/or coactivation of untargeted
      muscle groups.

PMID- 7713802
TI  - Myocardial edema, left ventricular function, and pulmonary hypertension.
AB  - Left ventricular dysfunction has been reported in both experimentally induced and
      clinical pulmonary hypertension. However, the mechanism by which pulmonary
      hypertension causes left ventricular dysfunction is unknown. We hypothesized that
      acute pulmonary hypertension causes left ventricular myocardial interstitial
      edema and that it is this edema that causes left ventricular dysfunction. In
      pulmonary artery-banded or sham-operated dogs, left ventricular diameter (septal
      free wall axis) and pressure were measured using sonomicrometry crystals and a
      micromanometer, respectively. These measurements were used to calculate preload
      recruitable stroke work (PRSW), an index of contractility, and the rate of active
      relaxation (tau) to assess systolic and diastolic left ventricular function,
      respectively. After 3 h of pulmonary arterial hypertension or control, the dogs
      were killed and the left ventricles were excised to determine wet-to-dry weight
      ratios. The wet-to-dry weight ratios were significantly higher in the pulmonary
      artery-banded dogs (3.57 +/- 0.12) than in the sham-operated dogs (3.41 +/-
      0.17). PRSW decreased to 56.8 +/- 30.3% of control after 3 h of pulmonary
      hypertension. tau Slowed significantly from 29.8 +/- 5.8 ms at baseline to 63.6
      +/- 30.4 ms after 3 h of pulmonary arterial hypertension. There were no
      differences in PRSW or tau in the sham-operated dogs. We conclude that pulmonary
      hypertension causes left ventricular myocardial interstitial edema, which results
      in both systolic and diastolic left ventricular dysfunction.

PMID- 7713803
TI  - Adaptations in muscle metabolism to prolonged voluntary exercise and training.
AB  - In previous research we established using a short-term (5-7 days) training model
      that increases in muscle oxidative potential are not a prerequisite for the
      characteristic energy metabolic adaptations (lower lactate, glycogen depletion,
      and phosphocreatine hydrolysis) observed during prolonged exercise. To
      investigate whether increased muscle aerobic potential further potentiates the
      metabolic adaptive response, seven healthy male volunteers [maximal O2 uptake
      (VO2max) = 45.1 +/- 1.1 (SE) ml.kg-1.min-1] engaged in an 8-wk training program
      consisting of 2 h of cycle exercise at 62% of pretraining VO2max 5-6 times/wk.
      Analysis of tissue samples obtained from the vastus lateralis after 60 min of
      exercise revealed that by 4 wk of training muscle lactate concentration,
      phosphocreatine hydrolysis, and glycogen depletion were depressed (all P < 0.05).
      Further training for 4 wk had no additional effect (P < 0.05). The ratio of
      fructose 6-phosphate to fructose 1,6-phosphate, an index of phosphofructokinase
      activity, was not altered with training. Muscle oxidative potential as estimated
      from the maximal activity of succinic dehydrogenase increased by 31% by 4 wk of
      training (P < 0.05) before plateauing during the final 4 wk of training. The
      increase in VO2max of 15.6% (P < 0.05) noted with training was also primarily
      expressed during the initial 4 wk. O2 uptake during submaximal exercise was
      unchanged. Because the metabolic response was similar in magnitude to that
      previously observed with short-term training, we conclude that, at least for the
      conditions of this study, the development of increased muscle aerobic potential
      is of minimal consequence on the magnitude of the energy metabolic adaptations
      examined.

PMID- 7713804
TI  - IMP metabolism in human skeletal muscle after exhaustive exercise.
AB  - This study addressed whether AMP deaminase (AMPD)myosin binding occurs with
      deamination during intense exercise in humans and the extent of purine loss from
      muscle during the initial minutes of recovery. Male subjects performed cycle
      exercise (265 +/- 2 W for 4.39 +/- 0.04 min) to stimulate muscle inosine 5'
      monophosphate (IMP) formation. After exercise, blood flow to one leg was
      occluded. Muscle biopsies (vastus lateralis) were taken before and 3.6 +/- 0.2
      min after exercise from the occluded leg and 0.7 +/- 0.0, 1.1 +/- 0.0, and 2.9 +/
      0.1 min postexercise in the nonoccluded leg. Exercise activated AMPD; at
      exhaustion IMP was 3.5 +/- 0.4 mmol/kg dry muscle. Before exercise, 16.0 +/- 1.6%
      of AMPD cosedimented with the myosin fraction; the extent of AMPD:myosin binding
      was unchanged by exercise. Inosine content increased about threefold during
      exercise and twofold more during recovery; by 2.9 min postexercise it was 0.43 +/
      0.02 mmol/kg dry muscle. IMP decreased 2.1 +/- 0.3 mmol/kg dry muscle with no
      change in total adenylates. Total purines declined significantly (P < 0.05)
      during the recovery period in the nonoccluded leg, consistent with a loss of
      purines to the circulation, whereas total purines were unchanged in the occluded
      leg. Regulation of muscle purine content is a dynamic process that must
      accommodate rapid changes due to degradation and efflux.

PMID- 7713805
TI  - Rat retrotrapezoid nucleus iono- and metabotropic glutamate receptors and the
      control of breathing.
AB  - We injected 10 nl (unilateral) of glutamate receptor antagonists or agonists into
      the region of the retrotrapezoid nucleus and measured the phrenic nerve and blood
      pressure responses. The rats were chloralose-urethan anesthetized, paralyzed,
      vagotomized, and ventilated, and each injection location was verified
      anatomically. Integrated phrenic amplitude was most reliably affected. The N
      methyl-D-aspartic acid (NMDA) antagonists 2-amino-5-phosphonopentanoic acid and 6
      cyano-7-nitroquinoxaline-2,3-dione (which affects both NMDA and non-NMDA
      receptors) both decreased baseline eucapnic phrenic amplitude and the CO2
      response. Glutamate increased phrenic amplitude in a dose-dependent manner, an
      effect blocked by prior injection of the NMDA and non-NMDA antagonists at the
      same site. The response duration depended on the duration of the glutamate
      injection: responses to 3-s injections lasted a few minutes, and responses to 60
      s injections lasted for > 30 min. The long-lasting effect was reproduced by
      injection of the metabotropic agonist 1(S),3(R)-aminocyclopentanedicarboxylic
      acid at 0.01-0.02 times the glutamate dose. We conclude that the rat
      retrotrapezoid nucleus has an endogenous source of glutamate that maintains
      eucapnic phrenic output and allows expression of the CO2 response. NMDA and
      possibly non-NMDA receptors are involved. Their stimulation increases phrenic
      output via ionotropic and metabotropic receptor processes with the latter
      resulting in long-lasting phrenic stimulation.

PMID- 7713807
TI  - Time course for exercise-induced alterations in insulin action and glucose
      tolerance in middle-aged people.
AB  - The purposes of this study were 1) to investigate glucose tolerance and insulin
      action immediately after exercise and 2) to determine how long the improved
      glucose homeostatic mechanisms observed 12-16 h after exercise persist. Nine
      (seven men, two women) moderately trained middle-aged (51 +/- 3 yr) subjects
      performed 45 min of exercise at 73 +/- 2% of peak O2 uptake for 5 days, followed
      by 7 days of inactivity. Oral glucose tolerance tests (OGTT; 75 g) were performed
      immediately postexercise (IPE; approximately 30 min) after the final exercise
      bout and 1, 3, 5, and 7 days after exercise. The incremental area under the
      plasma glucose curve was markedly higher IPE (355 +/- 82 mM.min) compared with
      those on days 1 (136 +/- 57 mM.min; P < 0.05) and 3 (173 +/- 62 mM.min; P <
      0.05). The glucose area was significantly higher on days 5 (213 +/- 80 mM.min)
      and 7 (225 +/- 84 mM.min) compared with those on days 1 and 3 (P < 0.05). The
      incremental insulin area IPE (3,729 +/- 1,104 microU.ml-1.min) was 43% higher
      compared with that on day 1 (2,603 +/- 635 microU.ml-1.min; P < 0.05) and 66%
      higher compared with that on day 3 (2,240 +/- 517 microU.ml-1.min; P < 0.05). The
      insulin area increased to 3,616 +/- 617 microU.ml-1.min after 5 days of
      inactivity (P < 0.05). An additional 48 h of inactivity did not result in any
      further increase in the plasma insulin response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713806
TI  - Refractory ceramic fibers activate alveolar macrophage eicosanoid and cytokine
      release.
AB  - Refractory ceramic fiber has been developed for industrial processes requiring
      materials with high thermal and mechanical stability. To evaluate the biological
      activity of this fiber, rat alveolar macrophages were exposed for < or = 24 h to
      0-1,000 micrograms/ml of refractory ceramic fiber, crocidolite asbestos, silica
      (fibrogenic particles), or titanium dioxide (a nonfibrogenic particle), and
      eicosanoid, tumor necrosis factor-alpha (TNF), and lactate dehydrogenase release
      were measured. Particle dimensions were determined by electron microscopy.
      Radioactivity coeluting with leukotriene B4 (LTB4) and immunoreactive LTB4 and
      TNF release increased after refractory ceramic fiber and were similar in
      magnitude after asbestos but less than after silica. For example, the total
      [3H]eicosanoid release increased 3.9-fold after refractory ceramic fiber, 4.6
      fold after asbestos, and 8.7-fold after silica. Refractory ceramic fiber and
      asbestos also have similar particle dimensions (diameter, length, and surface
      area). Inasmuch as macrophage-derived LTB4 and TNF are potent mediators in
      inflammatory events, including migration and activation of neutrophils, these
      findings suggest that refractory ceramic fiber can activate macrophages in vitro
      to release mediators relevant to in vivo findings of inflammation and fibrotic
      lung disease in laboratory animals.

PMID- 7713808
TI  - Effect of aging on beta 2-adrenergic receptor-stimulated flux of K+, PO4, FFA,
      and glycerol in human forearms.
AB  - beta-Adrenergic responses have been shown to decline with aging, particularly in
      the cardiovascular system. We infused terbutaline, a selective beta 2
      adrenoceptor agonist, into the brachial artery of 10 young (mean age 25 yr, range
      22-31 yr) and 9 elderly (mean age 73 yr, range 68-81 yr) healthy subjects to
      examine its effects on nutrient flux. Forearm K+, PO4, free fatty acid (FFA), and
      glycerol uptake were determined by measurement of forearm blood flow (using dye
      dilution) and brachial arterial and deep venous plasma substrate concentrations.
      Elderly subjects were less sensitive to terbutaline-mediated increases in forearm
      blood flow, net fluxes of K+, and glycerol but not net fluxes of FFA or PO4. The
      mean fitted slopes of each parameter vs. the log of the terbutaline
      concentration, a measure of forearm beta-adrenergic sensitivity, for young and
      elderly groups were 4.9 +/- 1.7 (SD) vs. 2.4 +/- 2.3 for forearm blood flow (P <
      0.05), 0.84 +/- 0.46 vs. 0.43 +/- 0.37 for K+ net flux (P < 0.05), -157 +/- 113
      vs. -26 +/- 26 for glycerol net flux (P < 0.01), -336 +/- 429 vs. -44 +/- 457 for
      FFA net flux (P = 0.11), and 0.31 +/- 0.24 vs. 0.18 +/- 0.16 for PO4 net flux (P
      = 0.14). Terbutaline promoted net uptake of K+ into skeletal muscle less well in
      the elderly, although net PO4 flux was similar in the two groups. Terbutaline
      stimulated vasodilation and net glycerol efflux but not FFA efflux were impaired
      with aging. These data demonstrate that heterogeneous changes in beta-adrenergic
      responses occur with aging.

PMID- 7713809
TI  - Developmental changes in chest wall compliance in infancy and early childhood.
AB  - Development of chest wall stiffness between infancy and adulthood has important
      consequences for respiratory system function. To test the hypothesis that there
      is substantial stiffening of the chest wall in the first few years of life, we
      measured passive chest wall compliance (Cw) in 40 sedated humans 2 wk-3.5 yr old.
      Respiratory muscles were relaxed with manual ventilation applied during the Mead
      Whittenberger technique. Respiratory system compliance (Crs) and lung compliance
      (Cl) were calculated from airway opening pressure, transpulmonary pressure, and
      tidal volume. Cw was calculated as 1/Cw = 1/Crs - 1/Cl during manual ventilation.
      Mean Cw per kilogram in infants < 1 yr old was significantly higher than that in
      children > 1 yr old (2.80 +/- 0.87 vs. 2.04 +/- 0.51 ml.cmH2O-1.kg-1; P = 0.002).
      There was an inverse linear relationship between age and mean Cw per kilogram (r
      = -0.495, slope -0.037; P < 0.001). In subjects with normal Cl during spontaneous
      breathing, Cw/spontaneous Cl was 2.86 +/- 1.06 in infants < 1 yr old and 1.33 +/-
      0.36 in older children (P = 0.005). We conclude that in infancy the chest wall is
      nearly three times as compliant as the lung and that by the 2nd year of life
      chest wall stiffness increases to the point that the chest wall and lung are
      nearly equally compliant, as in adulthood. Stiffening of the chest wall may play
      a major role in developmental changes in respiratory system function such as the
      ability to passively maintain resting lung volume and improved ventilatory
      efficiency afforded by reduced rib cage distortion.

PMID- 7713810
TI  - Role of angiotensin II in hemodynamic responses to dynamic exercise in miniswine.
AB  - Angiotensin II (ANG II) is a potent vasoconstrictor of splanchnic and renal
      resistance vessels. Because ANG II increases during exercise and blood flow in
      the splanchnic and renal circulations decreases, we tested the hypothesis that
      ANG II plays a role in arterial blood pressure and regional blood flow responses
      to treadmill running in the miniswine. Consequently, 11 pigs were instrumented
      with epicardial electrocardiogram leads and left atrial and aortic catheters to
      assess mean arterial blood pressure (MAP), heart rate (HR), myocardial
      contractility, cardiac output, and regional blood flow during treadmill running.
      Each animal exercised for 20 min at 80% of its maximal HR reserve. Exercise was
      performed in the absence and presence of the ANG II AT1 receptor antagonist
      losartan (15-20 mg/kg). ANG II AT1 receptor blockade attenuated the MAP and
      systemic vascular resistance responses to dynamic exercise but had no effect on
      cardiac output, HR, or myocardial contractility. In addition, blood flow
      increased and/or regional vascular resistance decreased in the heart, kidneys,
      stomach, small intestine, and colon, whereas the reverse occurred in the skin and
      spleen. These data suggest that ANG II contributes to the increase in MAP and
      redistribution of cardiac output associated with dynamic exercise.

PMID- 7713811
TI  - Effects of methysergide administration on edema formation at the site of scald.
AB  - Femoral blood flow (Qa), hind paw lymph flow (Qlym), and lymph-to-plasma protein
      concentration ratio (Clym/Cp) were monitored before and 4 h after 1) 5-s 100
      degrees C paw scald, 2) methysergide (1 mg/kg iv) 20 min before scald, 3)
      methysergide 30 min after scald, and 4) methysergide only. Before
      experimentation, hind paw venous pressure was elevated and maintained until
      steady-state Qa, Qlym, and minimal Clym/Cp levels were reached. The reflection
      coefficient (sigma d) was determined as 1 - minimal Clym/Cp; the filtration
      coefficient (Kf) was calculated. Methysergide alone caused no changes. Increases
      in Qa, Qlym, Clym/Cp, and Kf were identified in all scald groups. Compared with
      scald only animals, pre- and postscald methysergide blunted the increases in Qa,
      Qlym, Kf, and paw weight gain without an effect on sigma d. These data
      demonstrate that methysergide reduces edema formation at the site of scald,
      perhaps by modulating the burn-induced vasodilator response and/or by limiting
      the burn-induced increase in microvascular surface area.

PMID- 7713812
TI  - Time-dependent glycemic response to exercise in winter and spring in the
      subarctic.
AB  - Twenty healthy athletes exercised for 30 min at four different times (beginning
      at 1130 and 1630) in December (darkness period) and in April (18 h of daylight).
      Four hours after intake of a standardized meal, a 30-min bike exercise with an
      intensity of 60% maximal O2 uptake was performed. Blood samples (fingertip) were
      drawn at 1, 5, 10, and 30 min into exercise and 5, 10, and 30 min after
      termination of exercise for determination of blood glucose. Glucose values were
      normalized by reexpressing each as a percentage of the starting value. The total
      area under the glucose-time curves as well as the area below the starting value
      was calculated. Areas were tested for the effect of sex, time of day, and season
      by analysis of variance. For the group as a whole during exercise, a significant
      effect was found by analysis of variance for sex, time of exercise, and season.
      During recovery, significant differences were found for sex and time of exercise
      but not for season. The minimal integrated glucose response to exercise occurred
      in females, who also showed the most rapid return to baseline values during the
      recovery period. Exercise in the morning produced the smallest glucose response
      for both sexes and faster recovery compared with exercise in the afternoon. This
      was also the case overall for exercise in December compared with April. This
      finding implies that the glycemic response may be influenced by season and timing
      of exercise, which may be of importance for athletes involved in vigorous
      training and patients with diabetes mellitus.

PMID- 7713814
TI  - Heart rate and blood pressure variabilities during graded head-up tilt.
AB  - We investigated the responses of the frequency components of heart rate (HR) and
      blood pressure (BP) variabilities to progressive changes in autonomic activity
      induced by the graded head-up tilt technique in 12 normal subjects (age 19-27 yr)
      under the condition of frequency-controlled respiration (0.25 Hz). During low
      level tilt (0-30 degrees), the R-R interval was unchanged and the amplitude of
      the high-frequency (HF; 0.25 Hz) component of HR variability showed only a slight
      insignificant decrease. The amplitude of the low-frequency (LF; 0.04-0.15 Hz)
      component of HR variability increased progressively as the angle increased (P <
      0.05). During high-level tilt (30-90 degrees), the R-R interval and the HF
      amplitude of HR variability decreased progressively with tilt angle (P < 0.001
      for both). The LF amplitude of HR variability peaked at a tilt angle of 30
      degrees. The LF-to-HF ratio of HR variability and the LF amplitude of systolic
      and diastolic BP variabilities increased progressively as the tilt angle
      increased from 0 to 60 degrees (P < 0.001), although systolic and diastolic BPs
      were unchanged. These results suggest that mixed autonomic responses to
      orthostatic stress, which are thought to be mediated by both cardiopulmonary and
      arterial baroreflex mechanisms, can be distinguished by changes in the frequency
      components of HR and BP variabilities.

PMID- 7713813
TI  - Rapid tracer lactate influx into canine skeletal muscle.
AB  - This study evaluated the effects of various lactate transport inhibitors and
      competitors on rapid tracer lactate influx into the canine gastrocnemius
      plantaris muscle (GP). GPs of 25 anesthetized dogs were perfused with red blood
      cell-free media in situ. At 0.9 mM lactate concentration ([La]), GP oxygen uptake
      (2.6 +/- 0.1 ml.kg-1.min-1) and net lactate output (-0.039 +/- 0.007 mmol.kg
      1.min-1) were similar to values during blood perfusion. Rapid tracer lactate
      influx was inferred by a paired-tracer dilution method at nominal perfusate [La]
      values of 1, 5, 10, 25, and 50 mM. The maximal tracer influx rate (Umax)
      decreased significantly with each increase in unlabeled [La]. A saturation effect
      was suggested by the fact that percent inhibition of Umax began to reach a
      plateau at the higher unlabeled [La] values. The inhibition of Umax was 20.5 +/-
      2.9% at 5 mM, 34.1 +/- 3.3% at 10 mM, 47.3 +/- 2.7% at 25 mM, and 56.1 +/- 2.8%
      at 50 mM [La]. Umax was also inhibited by various inhibitors/competitors of
      lactate transport as follows (% inhibition): 50 mM alpha-cyano-4-hydroxy
      cinnamate (69.2 +/- 4.9%), 1.5 mM phloretin (25.4 +/- 5.5%), 0.1 mM 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (0.3 +/- 1.9%), 0.5 mM p
      chloromercuribenzenesulfonic acid (72.9%), 0.5 mM furosemide (+ 2.8%), 25 mM
      pyruvate (52.4 +/- 2.9%), and 50 mM DL-lactate (50.2 +/- 4.0%). These experiments
      support the notion that lactate influx into canine skeletal muscle is a function
      of both a linear (possible diffusive) component and a Michaelis-Menten (carrier
      mediated) component.

PMID- 7713815
TI  - Relationship between atrial natriuretic peptide and plasma volume during graded
      exercise with water immersion.
AB  - To assess the relationship between atrial natriuretic peptide (ANP) and the
      reduction in plasma volume (PV) during exercise, we measured changes in PV and
      ANP in seven male volunteers during treadmill exercise in air (AE) and with water
      immersion (WE) together with time control studies of rest in air and in water.
      Blood samples were collected from a catheter in the antecubital vein at exercise
      intensities of 32, 49, 65, and 78% of peak oxygen consumption (VO2). Plasma ANP
      in AE increased significantly from the resting value [15 +/- 1 (SE) pg/ml] only
      at 78% of peak VO2 (29 +/- 5 pg/ml), whereas ANP in WE increased significantly at
      exercise levels of > 49% of peak VO2 and reached 68 +/- 9 pg/ml at 78% of peak
      VO2. Although PV in AE and WE decreased significantly with VO2 of > 49% of peak
      VO2 (P < 0.01), the decrease from the resting value in WE was significantly
      greater than that in AE of > 65% of peak VO2 (P < 0.01) and the decreases at 78%
      of peak VO2 were -9.7 +/- 0.8 and -6.1 +/- 1.7%, respectively. The difference in
      the decrease in PV between AE and WE at corresponding VO2 correlated strongly
      with that in the increase in ANP (r = -0.97; P < 0.01). These results are
      consistent with the hypothesis that ANP may be involved in the fluid shift from
      the intra- to extravascular space during exercise.

PMID- 7713817
TI  - Model for a pump that drives circulation of pleural fluid.
AB  - Physical and mathematical models were used to study a mechanism that could
      maintain the layer of pleural fluid that covers the surface of the lung. The
      pleural space was modeled as a thin layer of viscous fluid lying between a
      membrane carrying tension (T), representing the lung, and a rigid wall,
      representing the chest wall. Flow of the fluid was driven by sliding between the
      membrane and wall. The physical model consisted of a cylindrical balloon with
      strings stretched along its surface. When the balloon was inflated inside a
      vertical circular cylinder containing a viscous fluid, the strings formed narrow
      vertical channels between broad regions in which the balloon pressed against the
      outer cylinder. The channels simulated the pleural space in the regions of lobar
      margins. Oscillatory rotation of the outer cylinder maintained a lubricating
      layer of fluid between the balloon and the cylinder. The thickness of the fluid
      layer (h), measured by fluorescence videomicroscopy, was larger for larger fluid
      viscosity (mu), larger sliding velocity (U), and smaller pressure difference
      (delta P) between the layer and the channel. A mathematical model of the flow in
      a horizontal section was analyzed, and numerical solutions were obtained for
      parameter values of mu, U, delta P, and T that matched those of the physical
      model. The computed results agreed reasonably well with the experimental results.
      Scaling laws yield the prediction that h is approximately (T/delta
      P)(microU/T)2/3. For physiological values of the parameters, the predicted value
      of h is approximately 10(-3) cm, in good agreement with the observed thickness of
      the pleural space.

PMID- 7713816
TI  - Protective effect of mepacrine on hypoxia-reoxygenation-induced acute lung injury
      in rats.
AB  - Mepacrine, a cell membrane stabilizer and inhibitor of phospholipase A2 (PLA2),
      exerts a protective effect on ischemia-reperfusion injury in heart; however, its
      effect in lungs has not been examined. This study aimed to determine whether
      mepacrine pretreatment attenuates ischemia-reperfusion lung injury simulated by
      hypoxia reoxygenation and to identify possible mechanisms for such protection.
      Acute lung injury was induced in Sprague-Dawley rats by ventilation with 5% CO2
      95% N2 and 5% CO2-95% air. Pretreatment with 0.06 mM mepacrine significantly
      attenuated the acute lung injury. Capillary filtration coefficient, lung weight
      gain, and protein concentration of lung lavage fluid were significantly lower in
      mepacrine-treated rats than in rats exposed to hypoxia reoxygenation alone.
      Steroid dexamethasone, another potential PLA2 inhibitor, had almost no protective
      effect. Mepacrine but not dexamethasone caused dose-dependent attenuation of the
      increase in leukocyte chemiluminescence produced by exposure to phorbol myristate
      acetate. Mepacrine also dose-dependently inhibited production of tumor necrosis
      factor-alpha (TNF-alpha) by human monocytes; dexamethasone was much less
      effective in decreasing TNF-alpha production. We conclude that mepacrine but not
      dexamethasone can significantly attenuate a hypoxia-reoxygenation-induced injury
      of the lung. This protective effect of mepacrine may not be the result of its
      inhibition of PLA2 but rather of its downregulation of oxygen radical production
      by circulating or resident leukocytes or its attenuation of TNF-alpha production
      by macrophages.

PMID- 7713818
TI  - Measurement of intestinal vascular capacitance in dogs: an application of blood
      pool scintigraphy.
AB  - To define relative changes in intestinal vascular capacitance, we developed a
      model that allowed us to construct intestinal vascular pressure-volume
      relationships (PVR). Thirteen alpha-chloralose-anesthetized and splenectomized
      dogs were studied using a pneumatic constrictor and a small catheter to change
      and measure portal venous pressure. A small lead sheet was placed beneath the
      abdominal wall. Relative changes in intestinal blood volume (IBV) were determined
      by in vivo blood pool scintigraphy with 99mTc-labeled erythrocytes and were
      expressed as percentages corrected for specific activity and abdominal wall
      radioactivity. PVRs were constructed using data recorded during graded inflations
      of the portal venous constrictor. The abdominal wall contributed 32.4 +/- 7.7%
      (SD) of the total counts. During a 4-h control period, PVRs varied by no more
      than 6% (of IBV). In the isolated intestinal circulation, the change in IBV was
      precisely proportional to the volume of blood added, indicating that this method
      can detect very small changes in volume (< or = 5 ml). Nitroglycerin (25
      micrograms.kg-1.min-1) increased capacitance by 20%. Although it measures only
      relative changes, the model is stable and sensitive, provides reproducible
      measurement of intestinal PVRs, and, with adaptation, may prove useful in patient
      studies.

PMID- 7713820
TI  - Ventilatory responses to cooling the ventrolateral medullary surface of awake and
      anesthetized goats.
AB  - The ventrolateral medulla (VLM) has been reported to be important as a source of
      tonic facilitation of dorsal respiratory neurons and as a site critical for
      respiratory rhythmogenesis. We investigated these theories in awake and
      anesthetized goats (n = 13) by using chronically implanted thermodes to create
      reversible neuronal dysfunction at superficial VLM sites between the first
      hypoglossal rootlet and the pontomedullary junction (area M (rostral) and area
      S). During halothane anesthesia (arterial PCO2 = 57.4 +/- 4.5 Torr), bilateral
      cooling (thermode temperature = 20 degrees C) of 60-100% of areas M and S for 30
      s produced a sustained apnea (46 +/- 4 s) that lasted beyond the period of
      cooling. While the animals were awake (arterial PCO2 = 36.0 +/- 1.9 Torr),
      cooling the identical region in the same goats resulted in a decrease
      (approximately 50%) in pulmonary ventilation, with a brief apnea seen only in one
      goat. Reductions in both tidal volume and frequency were observed. Qualitatively
      similar responses were obtained when cooling caudal area M-rostral area S and
      rostral area M, but the responses were less pronounced. Minimal effects were seen
      in response to cooling caudal area S. During anesthesia, breathing is critically
      dependent on superficial VLM neurons, whereas in the awake state these neurons
      are not essential for the maintenance of respiratory rhythm. Our data are
      consistent with these superficial VLM neuronal regions providing tonic
      facilitation to more dorsal respiratory neurons in both the anesthetized and
      awake states.

PMID- 7713819
TI  - Structural and functional characteristics of peripheral pulmonary parenchyma in
      golden hamsters.
AB  - Mechanical properties of the peripheral pulmonary parenchyma of freshly excised
      hamster lung tissue were examined to evaluate determinants of displacement
      tension relationships with regard to structural constituents of the alveolar
      wall. A tissue segment measuring 50 x 50 x 400-600 microns and consisting mostly
      of the alveolar wall was prepared from the lung parenchyma adjacent to the
      pleura. By use of a constant speed maneuver for extension and relaxation of this
      minute preparation, displacement-tension relationships of peripheral pulmonary
      parenchyma were examined in a bath filled with 37 degrees C physiological buffer
      solution. The specimen was repeatedly extended up to 20-40 mg, a little above a
      point resembling "yield" in displacement-tension relationships. Analyses of
      displacement-tension relationships constantly showed double exponential
      relations. The first component at the lower strain was approximated by sigma 1 =
      A1(e alpha 1 epsilon - 1) and the second component beyond the inflection (yield)
      point was sigma = s1 + s2 = A1(e alpha 1 epsilon - 1) + A2(e alpha 2 epsilon -
      1), where sigma, A, alpha, and epsilon represent stress, constant determined by
      tissue quantity, elasticity constant, and strain, respectively. Immersion of the
      lung specimen into elastase resulted in decreases of only alpha 1, and
      collagenase reduced alpha 2 but not alpha 1. Hyaluronidase, acetylcholine,
      ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and
      norepinephrine did not alter alpha 1 or alpha 2. These observations suggest that
      alpha 1 and alpha 2 of the peripheral pulmonary parenchyma are mechanical indexes
      of elastin and collagen characters, respectively.

PMID- 7713821
TI  - Effects on breathing of ventrolateral medullary cooling in awake goats.
AB  - Our objective was to investigate the role of the ventrolateral medulla (VLM) in
      the control of breathing during the awake state. In 17 awake adult goats,
      chronically implanted thermodes were used to cool the VLM and thereby cause
      reversible neuronal dysfunction in all or portions of the area between the first
      hypoglossal rootlet and the ponto-medullary junction (so-called area M (rostral)
      and area S). Within 5 s after the initiation of cooling, 60-100% of areas M and
      S, pulmonary ventilation (VE) decreased uniformly over conditions of eucapnia,
      hypercapnia, hypoxia, and exercise (P < 0.05). Between 10 and 20 s of cooling,
      the reduction in VE was approximately 10% greater during eucapnia and hypercapnia
      than during hypoxia and exercise (P < 0.05). For the remaining 10 s of cooling
      and for about 1 min after cooling, VE increased to and above control level.
      Cooling only rostral area M or only caudal area M-rostral area S affected
      breathing qualitatively in the same manner as when 60-100% of areas M and S were
      cooled. However, cooling caudal area S had effects that differed significantly (P
      < 0.05) from more rostral cooling in that the initial decrease in VE was
      attenuated and the subsequent increase was accentuated. The initial uniform
      decreased VE during cooling suggests that superficial VLM nonchemoreceptor
      neurons facilitate breathing. The subsequent relatively greater effect of cooling
      during eucapnia and hypercapnia probably reflects dysfunction of chemoreceptor
      related neurons that normally stimulate breathing. The stimulation of breathing
      during the later stages and after cooling may suggest that some VLM neurons
      inhibit breathing.

PMID- 7713822
TI  - Basal fat oxidation decreases with aging in women.
AB  - The present study tested the hypothesis that a decrease in basal fat oxidation in
      aging women is related to a loss of fat-free mass. Thirty-two nonsmoking women
      with a wide range of age (18-73 yr) were characterized for body composition
      (underwater weight), maximal aerobic capacity, and basal fat oxidation (indirect
      calorimetry). Results showed that fat oxidation was negatively correlated with
      age (r2 = 0.17, P = 0.017) but was positively correlated with the fat-free mass
      (r2 = 0.48, P < 0.0001) and with the level of aerobic fitness (maximal aerobic
      capacity) (r2 = 0.22, P = 0.007). Unexpectedly, fat oxidation had no relationship
      with fat mass (r2 = 0.07, P = 0.136). Partial correlation analysis showed that
      the decline in fat-free mass, and not the age or maximal O2 consumption, was the
      best single predictor of the decline in basal fat oxidation. These results
      support the theory that a decrease in fat oxidation with advancing age in healthy
      women is associated with a decrease in the fat-free mass and not age per se.
      Interventions that increase or preserve the quantity of fat-free mass (e.g.,
      exercise training) may enhance fat oxidation and thus lessen the age-associated
      adiposity in women.

PMID- 7713823
TI  - Unidirectional sodium and potassium flux in myogenic L6 cells: mechanisms and
      volume-dependent regulation.
AB  - To clarify the relative participation of particular ion transport systems in net
      univalent cation fluxes under basal conditions and altered volume of skeletal
      muscle-derived cells, the effect of inhibitors of the Na(+)-K+ pump (ouabain),
      univalent ion cotransporters [bumetanide, furosemide, and (dihydroindenyl)oxy
      alkanoic acid], and N+/H+ exchanger (ethylisopropylamiloride) on 86Rb and 22Na
      fluxes has been studied in L6 myoblasts incubated in isosmotic (320 mosmol/kg)
      and anisosmotic media. Under the isosmotic condition, the relative contribution
      of ouabain-inhibited and ouabain-insensitive bumetanide-inhibited component of
      86Rb influx was approximately 15-20 and 60%, respectively. 22Na influx was
      inhibited by bumetanide and ethylisopropylamiloride by 25 and 15%, respectively.
      Under isosmotic conditions, an increase of L6 cell volume was observed after
      addition of extracellular acetylcholine, extracellular K(+)-induced
      depolarization, or lowering of the pH of the incubation medium. High
      extracellular glutathione (150 microM) did not affect the cell volume of the
      muscle-derived cells bathed in isosmotic medium. Results of this study suggest
      that the bumetanide-inhibited component of K+ influx plays a key role in the
      adjustment of transmembrane K+ gradient in L6 myoblasts. The Na+/H+ exchanger
      appears to be important in regulatory volume increase.

PMID- 7713824
TI  - How mode of stimulus affects the relative contribution of elastance and
      hysteresivity to changes in lung tissue resistance.
AB  - Challenges with high concentrations of constrictor agonist delivered by
      intravenous vs. aerosol result in different modifications of the mechanical
      properties of lung tissues. We questioned whether low doses of a smooth muscle
      agonist administered via different routes (aerosol, i.v. bolus, i.v. continuous
      infusion) or an increase in positive end-expiratory pressure (PEEP) would result
      in different mechanical perturbations of lung tissues. Tracheal and alveolar
      pressures and flow were measured in open-chest mechanically ventilated (frequency
      1 Hz, tidal volume 10 ml/kg, PEEP 4 cmH2O) rats under baseline conditions and
      after administration of low doses of methacholine or after increases in PEEP. We
      calculated lung elastance (EL), lung resistance, and tissue resistance (Rti) by
      fitting the equation of motion to changes in tracheal and alveolar pressures.
      Airway resistance and hysteresivity (eta) were derived from the above
      measurements. For comparable increases in Rti, the aerosol and PEEP groups showed
      large increases in EL with a decrease in eta, whereas the two intravenous groups
      showed large increases in eta with smaller increases in EL. The largest
      contribution of eta to the overall increase in Rti was seen in the intravenous
      bolus group. When induced changes in EL vs. induced changes in eta were plotted,
      different relationships were found for the four groups. We conclude that despite
      similar increases in Rti a different kind of mechanical perturbation occurred in
      the lung tissues that depended on the nature of the stimulus.

PMID- 7713827
TI  - "Effects of hypoxia and hypercapnia on the Hering-Breuer reflex of the conscious
      newborn rat".

PMID- 7713825
TI  - Influence of muscle glycogen on glycogenolysis and glucose uptake during exercise
      in humans.
AB  - To examine the effects of alterations in preexercise muscle glycogen availability
      on glycogenolysis and glucose uptake during exercise, 12 active but untrained men
      [22.8 +/- 1.6 (SE) yr, 71.7 +/- 2.0 kg, peak pulmonary oxygen uptake 3.85 +/-
      0.16 l/min] were studied during 40 min of cycle ergometer exercise at 65-70% peak
      pulmonary oxygen uptake on two separate occasions, at least 1 wk apart.
      Preexercise muscle glycogen concentrations were manipulated by having the
      subjects perform glycogen-lowering exercise either 24 or 48 h before a trial, in
      combination with either high or low dietary carbohydrate intake. In series 1 (n =
      7), increasing muscle glycogen from 90.3 +/- 6.0 to 124.7 +/- 10.8 mmol/kg wet wt
      increased muscle glycogenolysis during exercise (62.7 +/- 7.9 vs. 49.1 +/- 6.6
      mmol/kg; P < 0.05). Similarly, in series 2 (n = 5) when muscle glycogen was
      reduced from 96.2 +/- 6.6 to 53.7 +/- 6.0 mmol/kg, glycogen utilization during
      exercise was reduced from 51.8 +/- 4.6 to 28.3 +/- 3.8 mmol/kg (P < 0.05). The
      altered muscle glycogen utilization was associated with alterations in
      carbohydrate oxidation during exercise, without effect on tracer ([3H]glucose)
      determined glucose uptake. These results indicate that preexercise muscle
      glycogen availability influences muscle glycogenolysis, but not glucose uptake,
      during exercise.

PMID- 7713826
TI  - Hypertrophy and proliferation of skeletal muscle fibers from aged quail.
AB  - The purpose of this study was to determined whether fibers in the anterior
      latissimus dorsi (ALD) muscle from aged Japanese quail have decreased
      hypertrophic or proliferative responses to 30 days of stretch overload compared
      with fibers from adult birds. Two groups of quail were studied, 12-wk-old quail
      (adult; n = 16) and 90-wk-old quail (aged; n = 16). The left wing of each bird
      was overloaded with a weight corresponding to 10% of the bird's body weight, and
      the right wing served as the intra-animal control. Quails were killed after 30
      days of stretch overload. Total fiber number was quantified by counting all the
      fibers in a transverse section from the midbelly of the ALD muscle. ALD muscles
      in aged quails retained the capacity to increase their muscle mass (145%), total
      fiber number (49%), and fiber cross-sectional area (54%) in response to stretch
      overload. The ALD muscle in aged quail had a significantly lower increase in
      muscle mass (33%) and mass corrected for nonmuscle tissue (36%) compared with the
      ALD from young adult birds. Age had no effect on fiber type distribution shifts
      with stretch. These results suggest that although muscles in old birds have a
      substantial ability to adapt to enlarge, stretch-induced hypertrophy is
      attenuated in muscles from old quail.

PMID- 7713828
TI  - Mechanical load affects growth and maturation of skeletal muscle grafts.
AB  - The purpose of our study was to determine whether the early patterns of growth
      and maturation of regenerating soleus muscle grafts are sensitive to alterations
      in mechanical load. We hypothesized that decreased and increased mechanical
      loading of grafts would reduce and accelerate, respectively, the rate and
      magnitude of growth and impair and enhance, respectively, the pattern of
      maturation. On day 0, soleus muscles were grafted and rats were assigned to one
      of three groups: cage sedentary (normal load), hindlimb suspension (decreased
      load), or ablation of synergist muscle (increased load). From days 7 to 35, graft
      mass in cage-sedentary rats increased at a rate of 1.85 mg mass/day. Rates were
      less for grafts of suspended rats and greater in grafts of ablated rats (-1.06
      and 3.89 mg mass/day, respectively; P < 0.01). Neonatal myosin heavy chain (MHC)
      in grafts reached 10 +/- 1.6% of total MHC at day 7 for cage-sedentary rats,
      whereas in the suspended animals it reached 11 +/- 2.4% of total MHC at day 14.
      At days 21 and 35, grafts from the suspended animals had a lower proportion of
      slow MHC (45 +/- 2.4%) than did grafts from the control and ablated groups (95 +/
      1.5%; P < 0.05). Decreased mechanical load impaired the rate and degree of
      growth and maturation during regeneration, whereas increased mechanical load
      enhanced growth characteristics but not maturation.

PMID- 7713829
TI  - Effects of exercise intensity on insulin sensitivity in women with non-insulin
      dependent diabetes mellitus.
AB  - Exercise enhances insulin sensitivity in people with non-insulin-dependent
      diabetes mellitus (NIDDM), but the intensity of exercise necessary to optimize
      the effect is unknown. Eight women with NIDDM were studied on a metabolic ward in
      each of three conditions: 1) low-intensity exercise (LO) that consisted of
      treadmill walking at 50% of maximal O2 consumption on days 1 and 2, 2) high
      intensity exercise (HI) that consisted of walking at 75% of maximal O2
      consumption, and 3) no exercise (NX). The duration of exercise was adjusted so
      that energy expenditure was equal in both exercise conditions. On day 3, glucose,
      [6,6-2H]glucose, and insulin were infused at fixed rates for 3 h. Insulin
      sensitivity was determined both by steady-state plasma glucose concentration and
      rate of glucose disposal per unit plasma insulin. Steady-state plasma glucose
      concentration and rate of glucose disposal per unit plasma insulin were almost
      identical after LO or HI; values were significantly greater than after NX. Plasma
      glucose response to a test meal was the same among the three conditions, but
      plasma insulin response was lower for HI and LO compared with NX. We conclude
      that under these conditions LO is as effective as HI in enhancing insulin
      sensitivity in people with NIDDM.

PMID- 7713830
TI  - Beta-adrenoceptor blockade and skeletal muscle energy metabolism during endurance
      exercise.
AB  - Twelve healthy male volunteers cycled to exhaustion at a workload corresponding
      to 70% of maximal aerobic power after administration of 80 mg of the beta 1+2
      adrenoceptor antagonist propranolol and after administration of placebo by mouth.
      Exercise times until exhaustion were 39 +/- 7 and 86 +/- 7 min in the propranolol
      and placebo groups, respectively. Muscle inosine 5'-monophosphate content was
      significantly increased above resting levels at exhaustion after placebo. At
      exhaustion after propranolol, inosine 5'-monophosphate was not increased
      significantly and was lower than at exhaustion after placebo. No changes in ATP
      and the total adenine nucleotide content during exercise were found in the two
      tests. Muscle glycogen content was significantly reduced at exhaustion after
      placebo as well as after propranolol, but the levels were still significantly
      higher at exhaustion after propranolol than after placebo. No evidence for a
      shift in glycogen utilization among types I, IIa, and IIb fibers after
      propranolol was found. The results show that neither an imbalance between ATP
      utilization and ATP regeneration nor premature glycogen depletion, either in the
      whole muscle or in specific muscle fiber types, provides a satisfactory
      explanation for the premature fatigue during endurance exercise after
      propranolol.

PMID- 7713831
TI  - Hypothermic effect of melatonin and nocturnal core body temperature decline are
      reduced in aged women.
AB  - In young humans, the nocturnal rise of the hypothermic hormone melatonin
      generates 40-50% of the circadian core body temperature (Tc) decline. The
      nocturnal Tc decline is reduced with aging in men. In this study we investigated
      whether a similar attenuation occurs in women and whether it is associated with a
      reduced serum concentration and/or action of melatonin. The circadian rhythms of
      melatonin and Tc (measured in the vagina) and the responses of both Tc (measured
      into the auricolar canal) and finger skin temperature to melatonin administration
      (100 mg at 0800) were investigated in two experiments involving young (22-32 yr)
      and aged (54-62 yr) women. In aged women, the nocturnal onset of the melatonin
      rise was phase advanced and Tc decline and Tc rhythm amplitude were reduced (P <
      0.0005). The serum melatonin concentrations in aged women were similar to those
      of young women, but the melatonin capability to reduce Tc and increase skin
      temperature was markedly impaired. Our data show that, in women, an aging
      associated reduction of temperature responses to melatonin is probably involved
      in inducing an attenuation of the nocturnal Tc decline and circadian Tc rhythm
      amplitude.

PMID- 7713832
TI  - Predicting heart rate response to various metabolic rates, environments, and
      clothing.
AB  - A mathematical model that describes heart rate (HR) responses to different
      combinations of metabolic levels, climatic conditions, and clothing ensembles was
      developed. The database that served to construct the model consisted of 48
      variations representing a wide range of environmental conditions, clothing
      ensembles, and metabolic rates. The model, which correlates highly with the
      observed values (r = 0.88, P < 0.0001), is based on physiological and
      environmental parameters: HR = 57.1 + 0.6HRi + [0.07M - 19.06 - 0.011(Emax -
      Ereq)] log t, where HRi is initial HR in beats per minute (at rest before the
      exposure), t is the time of exposure in minutes, M is the metabolic rate in
      watts, Ereq is the required sweat evaporation for thermal equilibrium in watts,
      and Emax is the maximal evaporative capacity of the environment in watts. The
      model's validity was tested by using two independent databases representing wide
      ranges of conditions; the correlation between measured and predicted values was
      found to be highly significant (r = 0.83, P < 0.001 and r = 0.77, P < 0.001,
      respectively). In summary, the present study suggests a valid predictive model
      for HR that overcomes some of the difficulties observed in other models.

PMID- 7713833
TI  - Human pulmonary vascular and venous compliances are reduced before and during
      left-sided heart failure.
AB  - Human pulmonary vascular and venous compliances were measured in 41 patients with
      or without left-sided heart failure. Two methods were used. Method 1 was based on
      analysis of pulmonary capillary wedge (PCW) pressure tracings according to Cv,PCW
      = (SF/100)(0.075PCW + 0.90)SV/[(v - d)PCW + 1], where Cv,PCW is compliance of
      pulmonary venous system, SF is systolic fraction of pulmonary venous flow
      [related to pulmonary capillary wedge pressure (PCW) as SF = 82 - 2.01PCW], (v -
      d)PCW is pulse pressure in PCW position, and SV is stroke volume. The (0.075PCW +
      0.90) term equals k", i.e., systolic run-off ratio. Method 2 was used to measure
      to pulmonary vascular volume-pressure (V-P) relationship and pulmonary vascular
      compliance (Cvasc) and is based on measurement of pulmonary blood volume (PBV)
      and its increase with passive elevation of the legs to calculate Cvasc. Assuming
      the proportion of blood entering pulmonary venous system (in increase of PBV)
      during passive leg elevation to be 0.8, pulmonary venous compliance (Cv,PBV) was
      calculated as Cv,PBV = 0.8Cvasc. Cv,PCW correlated fairly closely with Cv,PBV (r
      = 0.81, coefficient of variation = 31%). This fair agreement between two
      independent methods suggests strongly that both methods may be valid, although
      other interpretations are possible. Cv,PCW, Cvasc, and Cv,PBV decreased going
      from New York Heart Association class I to classes II and III. When PBV was
      plotted vs. PCW, average V-P line for class II patients was flatter and shifted
      downward to the right compared with that for class I. This suggests pulmonary
      vasoconstriction as well as other factors. Average V-P line for class III
      patients is flatter but not displaced compared with that for class II. Another
      previously reported series of 50 patients, most of whom had ischemic heart
      disease, are included in this study.

PMID- 7713834
TI  - Effects of strength and endurance training on thigh and leg muscle mass and
      composition in elderly women.
AB  - The effects of 18 wk of intensive strength and endurance training on knee
      extensor, knee flexor, and lower leg muscle mass and composition were studied in
      76- to 78-yr-old women. Muscle cross-sectional area (CSA), lean tissue CSA, and
      relative proportion of fat were determined using computed tomography. The
      strength-trained women increased their total muscle lean tissue CSA of the thigh
      (1.5%; P = 0.035), quadriceps CSA (4.5%; P = 0.021), quadriceps lean tissue CSA
      (5.8%, P = 0.009), and mean Hounsfield unit of the lower leg muscles (11.2%; P =
      0.035) compared with the changes that occurred in the control group during the
      experiment. The change in quadriceps lean tissue CSA because of the strength
      training was also significant compared with that in the endurance group. The
      relative proportion of fat within the quadriceps muscle decreased due to the
      strength training compared with the changes that occurred in the endurance group.
      The results show that intensive strength training can induce skeletal muscle
      hypertrophy in elderly women and thereby also reduce the relative amount of
      intramuscular fat, whereas the effects of endurance training are negligible.

PMID- 7713836
TI  - Is walking a random walk? Evidence for long-range correlations in stride interval
      of human gait.
AB  - Complex fluctuations of unknown origin appear in the normal gait pattern. These
      fluctuations might be described as being 1) uncorrelated white noise, 2) short
      range correlations, or 3) long-range correlations with power-law scaling. To test
      these possibilities, the stride interval of 10 healthy young men was measured as
      they walked for 9 min at their usual rate. From these time series, we calculated
      scaling indexes by using a modified random walk analysis and power spectral
      analysis. Both indexes indicated the presence of long-range self-similar
      correlations extending over hundreds of steps; the stride interval at any time
      depended on the stride interval at remote previous times, and this dependence
      decayed in a scale-free (fractallike) power-law fashion. These scaling indexes
      were significantly different from those obtained after random shuffling of the
      original time series, indicating the importance of the sequential ordering of the
      stride interval. We demonstrate that conventional models of gait generation fail
      to reproduce the observed scaling behavior and introduce a new type of central
      pattern generator model that successfully accounts for the experimentally
      observed long-range correlations.

PMID- 7713835
TI  - Inhaled nitric oxide does not alter the longitudinal distribution of pulmonary
      vascular resistance.
AB  - Because the effects of inhaled nitric oxide (NO) may be localized to its site of
      delivery, we studied the effects of inhaled NO on the longitudinal distribution
      of pulmonary vascular resistance during pulmonary hypertension in perfused rabbit
      lungs. Before NO administration, pulmonary hypertension was produced by infusion
      of the thromboxane A2 mimetic U-46619 in all lungs. Pulmonary vascular resistance
      was divided into arterial, microvascular, and venous components by arterial and
      venous occlusion techniques. In the buffer-perfused lung, all doses of inhaled NO
      (5, 20, and 80 ppm) produced small decreases (approximately 3 mmHg) in pulmonary
      arterial pressure (Ppa), with equivalent proportional reductions in all segmental
      vascular resistances. Similar results were obtained after an extended inhaled NO
      dose range of 20, 80, and 240 ppm. In the buffer-perfused lung, inhibition of
      endogenous NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME)
      potentiated the effects of U-46619. Subsequent inhaled NO administration produced
      larger decreases (approximately 7 mmHg) in Ppa with equivalent proportional
      reductions in all segmental vascular resistances. In the blood-perfused lung, L
      NAME did not alter baseline pulmonary pressures. Administration of inhaled NO
      during U-46619-induced pulmonary hypertension produced dose-related decreases in
      Ppa. The highest dose (80 ppm) of inhaled NO decreased Ppa by 3.5 mmHg, with
      equivalent proportional reductions in all segmental vascular
      resistances.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713837
TI  - Characterization of a density-corrected ultrasonic pneumotachometer for horses.
AB  - A density-corrected ultrasonic pneumotachometer designed specifically for horses
      (UF202) was evaluated and characterized with the aid of a custom-built apparatus.
      UF202 provided voltage outputs for airflow through and gas density within the
      flowhead. Baseline stability for flow channel output (VUF202) was < 0.35% full
      scale (FS), and VUF202 was linear over a range of +/- 50 l/s (R2 > or = 0.9976).
      Under optimal conditions, VUF202 accuracy was determined to be +/- 1.00% FS and
      repeatability was +/- 0.78% FS. VUF202 resolution was 24 ml/s. The rise time for
      VUF202 was 18 ms, and the -3-dB point was 18 Hz; digital compensation provided a
      flat frequency response to 32 Hz. VUF202 gain appeared to be stable over a period
      of 8 days. Density channel output (PUF202) was linear over a range of 1.11-1.23
      g/l (R2 > or = 0.9645). PUF202 accuracy was calculated to be +/- 0.50% FS, and
      PUF202 repeatability was determined to be +/- 0.30% FS. Resistance of the
      flowhead was determined to be 0.013 cmH2O.l-1.s at a flow of 40 l/s. On the basis
      of this study, we conclude that UF202 should facilitate accurate measurement of
      breath-by-breath airflow of exercising horses.

PMID- 7713839
TI  - Hypercapnia during exercise in asthmatic subjects.

PMID- 7713838
TI  - Age dependence of myosin heavy chain transitions induced by creatine depletion in
      rat skeletal muscle.
AB  - This study was designed to test the hypothesis that myosin heavy chain (MHC)
      plasticity resulting from creatine depletion is an age-dependent process. At
      weaning (age 28 days), rat pups were placed on either standard rat chow (normal
      diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine
      analogue beta-guanidinopropionic acid [creatine depletion juvenile (CDJ) group].
      Two groups of adult rats (age approximately 8 wk) were placed on the same diet
      regimens [normal diet adult and creatine depletion adult (CDA) groups]. After 40
      days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult
      groups), animals were killed and several skeletal muscles were removed for
      analysis of creatine content or MHC distribution. In the CDJ group, creatine
      depletion (78%) was accompanied by significant shifts toward expression of slower
      MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine
      depletion in adult animals did not result in similar shifts toward slow MHC
      isoform expression in either muscle type. The results of this study indicate that
      there is a differential effect of creatine depletion on MHC transitions that
      appears to be age dependent. These results strongly suggest that investigators
      contemplating experimental designs involving the use of the creatine analogue
      beta-guanidinopropionic acid should consider the age of animals to be used.

PMID- 7713840
TI  - Responses of rat mesenteric arteries to norepinephrine during exposure to heat
      stress and acidosis.
AB  - Both cardiovascular abnormalities and metabolic acidosis can be prominent in heat
      stroke and may contribute to morbidity and mortality in heat stroke victims. Thus
      the effects of heat stress and/or low pH on the responses of rat mesenteric
      arteries (approximately 300 microns) to norepinephrine (NE; 10(-8)-10(-5) M) and
      acetylcholine (ACh; 10(-5) M) were examined. Arteries (5-7/group) were isolated,
      cannulated with micro-pippettes, placed under constant intraluminal pressure (50
      mmHg), and then examined during 60-min exposures to either 1) 37, 42, or 43
      degrees C or 2) 37 or 42 degrees C under conditions of low pH (pH = 7.0 by
      addition of 1 N HCl). Contractile responses to NE remained unaltered during
      exposure to 42 and 43 degrees C. When arteries were returned from that elevated
      temperature back to 37 degrees C for 30 min, enhanced (P < 0.05) contractile
      responses to NE were observed. Exposure to low pH depressed contractile responses
      to NE to a similar extent in arteries tested at 37 or 42 degrees C. Dilations to
      ACh were not altered by exposure to 42 degrees C, regardless of pH conditions,
      but were progressively reduced during the 43 degrees C (P = 0.09) exposure.
      Arteries exposed to NE demonstrated vasomotion. The NE-induced vasomotion, while
      maintained at 37 degrees C, was reduced (P < 0.05) by exposure to 43 degrees C.
      In conclusion, the contractile response to NE in mesenteric arteries was not
      altered by heat stress per se (up to 43 degrees C) but was depressed by low pH.
      The latter response was not potentiated by heat stress.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7713841
TI  - Stability of GLUT-1 and GLUT-4 expression in perfused rat muscle stimulated by
      insulin and exercise.
AB  - In vivo exercise and insulin may change the concentrations of GLUT-4 protein and
      mRNA in muscle. We studied in vitro whether adaptations in glucose transporter
      expression are initiated during a single prolonged period of contractions or
      during insulin stimulation. Rat hindquarters were perfused at 7 mM glucose for 2
      h with or without insulin (> 20,000 microU/ml) while the sciatic nerve of one leg
      was stimulated to produce repeated tetanic contractions. During electrical
      stimulation, contraction force decreased 93 +/- 1% (SE; n = 26) and muscle
      glycogen was markedly diminished (P < 0.05). Both contractions and insulin
      markedly increased glucose transport and uptake (P < 0.05). At the end of
      contractions, glycogen was higher in the presence of than in the absence of
      insulin (24 +/- 4 vs. 14 +/- 3 mumol/g for the soleus and 13 +/- 2 vs. 8 +/- 1
      mumol/g for the red gastrocnemius, respectively; P < 0.05). In nonstimulated
      muscle, glucose transporter mRNA and protein concentrations were higher in the
      soleus than in the white gastrocnemius (GLUT-4 mRNA 184 +/- 18 vs. 131 +/- 36
      arbitrary units; GLUT-1 mRNA 173 +/- 29 vs. 114 +/- 26 arbitrary units; GLUT-4
      protein 0.96 +/- 0.09 vs. 0.46 +/- 0.03 arbitrary units; GLUT-1 protein 0.41 +/-
      0.08 vs. 0.19 +/- 0.05 arbitrary units, respectively; P < 0.05). These
      concentrations were not changed by contractions or insulin. In conclusion, GLUT-1
      and GLUT-4 mRNA and protein levels are higher in slow-twitch oxidative than in
      fast-twitch glycolytic fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713842
TI  - Effects of hypoxia and hypercapnia on the Hering-Breuer reflex of the conscious
      newborn rat.
AB  - We asked whether hypoxia and hypercapnia, singly or combined, affect the lung
      volume-dependent ventilatory inhibition [Hering-Breuer (HB) reflex] in newborn
      rats. Conscious rats 2, 5, and 8 days old were breathing in a flow
      plethysmograph. Mean lung volume was increased by applying a negative body
      surface pressure of 6 or 12 cmH2O. HB reflex was quantified as the inhibitory
      ratio (IR) of the apnea during the inflation expiratory time (TEinfl) to the
      control expiratory time (TEc), i.e., IR = TEinfl/TEc. In normoxia-normocapnia
      (control), IR with 6 cmH2O was approximately 8-12 at all ages and approximately
      doubled with inflation at 12 cmH2O. In hypoxia (HPX; 10% O2) or hypercapnia
      (HPCN; 3% CO2), IR decreased at 8 days, whereas it did not differ from the
      control value at 2 and 5 days. In HPX + HPCN, IR decreased at all ages. In HPX
      (at both 6- and 12-cmH2O inflations), in HPCN (6 cmH2O), or in HPX + HPCN (6 and
      12 cmH2O), IR decreased significantly more at 8 days than at 2 days. Metabolic
      rate, simultaneously measured, decreased during HPX or HPX + HPCN by a similar
      amount at all ages. The ventilatory response to HPX or to HPCN was significantly
      more pronounced at 8 days than at 2 days. We conclude that, during the early
      postnatal development of the rat, HPX or HPCN, singly or combined, reduces the HB
      reflex inhibition in the oldest pups, with minimal or no effects in the youngest.
      These developmental differences cannot be explained by differences in metabolic
      drive on ventilation but are contributed to by differences in chemosensitivity.

PMID- 7713843
TI  - Quartz inactivates alpha 1-antiproteinase: possible role in mineral dust-induced
      emphysema.
AB  - Occupational exposure to some types of mineral particles has been shown to be
      associated with the development of emphysema, but the mechanism of this process
      is unknown. Because many mineral particles are known to catalyze the formation of
      active oxygen species in aqueous solution, we hypothesized that mineral particles
      could oxidatively inactive antiproteinases, leading to an imbalance between
      protease and antiprotease activities, events similar to those believed to occur
      with cigarette smoke. To test this hypothesis, human alpha 1-antiproteinase
      (alpha 1-AP) was incubated with suspensions of freshly ground or aged quartz, and
      antiproteolytic activity was determined by using porcine pancreatic elastase.
      Increasing concentrations of quartz were associated with increasing losses of
      antiproteolytic activity; this effect could be prevented by catalase. Freshly
      ground quartz was more active than aged quartz. Western blot analysis for alpha 1
      AP showed abnormal banding, suggesting that porcine pancreatic elastase-alpha 1
      AP complex formation was impaired by silica exposure. Chemical assay of aqueous
      quartz suspensions demonstrated production of hydrogen peroxide; incubation of
      alpha 1-AP with hydrogen peroxide caused a dose-dependent loss of antiproteolytic
      activity, and this also could be prevented by catalase. We conclude that, at
      least in vitro, quartz can inactivate alpha 1-AP through a hydrogen peroxide
      mediated mechanism and that oxidative loss of antiproteinase activity could play
      a role in mineral dust-induced emphysema.

PMID- 7713845
TI  - BW-755C diminishes smoke-induced pulmonary edema.
AB  - Pulmonary edema following smoke inhalation is due to the chemical toxins in smoke
      and not to the heat. We have shown that acrolein, a common component of smoke,
      induces pulmonary edema, perhaps via release of leukotrienes. We, therefore,
      hypothesized that acrolein, a component of smoke from burning cotton, might have
      a major role in producing pulmonary edema in sheep after cotton smoke inhalation
      and that BW-755C, a combined cyclo- and lipoxygenase inhibitor, would prevent the
      edema, whereas indomethacin, a cyclooxygenase inhibitor, would not. In control
      anesthetized sheep (n = 7), 128 breaths of cotton smoke induced no change in
      pulmonary arterial pressure but induced increases (P < 0.05) in pulmonary lymph
      flow from 4.4 +/- 0.8 (SE) to 15 +/- 2.7 ml/h, lymph protein flux from 0.25 +/-
      0.08 to 0.80 +/- 0.16 g/h, and blood-corrected wet-to-dry weight ratios from a
      normal value of 3.8 +/- 0.07 (n = 9) to 4.5 +/- 0.18. Indomethacin (n = 6) did
      not significantly prevent these changes, whereas BW-755C decreased lung lymph
      flow change from 5 +/- 1 to 7 +/- 2 ml/h (P = NS), lymph protein flux from 0.25
      +/- 0.08 to 0.35 +/- 0.1 g/h (P = NS), and weight-to-dry ratio from normal to 3.9
      +/- 2.1 (P = NS). These data suggest leukotrienes may have a role in producing
      cotton smoke-induced noncardiogenic pulmonary edema.

PMID- 7713846
TI  - Effect of excess dietary salt on calcium metabolism and bone mineral in a
      spaceflight rat model.
AB  - High levels of salt promote urinary calcium (UCa) loss and have the potential to
      cause bone mineral deficits if intestinal Ca absorption does not compensate for
      these losses. To determine the effect of excess dietary salt on the osteopenia
      that follows skeletal unloading, we used a spaceflight model that unloads the
      hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on
      diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on
      diets containing 8% salt (HiNa) and 0.2% C (LoCa). Final body weights were 9-11%
      lower in S than in control rats (C) in both experiments, reflecting lower growth
      rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on
      HiNa diets and was twofold higher in S than in C transiently during unloading.
      Net intestinal Ca absorption was consistently 11-18% lower in S than in C. Serum
      1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was
      increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absorption
      in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss
      did not appear to affect the osteopenia induced by unloading. Although any
      deficit in bone mineral content from HiNa diets may have been too small to detect
      or the duration of the study too short to manifest, there were clear differences
      in Ca metabolism from control levels in the response of the spaceflight model to
      HiNa diets, indicated by depression of intestinal Ca absorption and its
      regulatory hormone.

PMID- 7713844
TI  - Exhaled nitric oxide in isolated pig lungs.
AB  - Endothelium-derived nitric oxide (NO) is an important regulator of vascular
      resistance. Low concentrations of NO have been recorded in the exhaled breath of
      spontaneously breathing animals and humans. To determine whether NO synthesis in
      the lung contributes to the NO measured in the breath, we measured the
      concentration of NO in the exhaled air of isolated perfused and ventilated
      porcine lungs by using a chemiluminescence method. With NO-free normoxic
      ventilation (21% O2-5% CO2-74% N2) of eight porcine lungs perfused with a Krebs
      dextran and albumin perfusate, baseline exhaled NO was 5.8 +/- 1.8 parts per
      billion (ppb) and pulmonary vascular resistance (PVR) was 8.9 +/- 1.8 mmHg.l
      1.min. Hypoxic ventilation (5% O2-5% CO2-90% N2) caused a fall in NO to 3.6 +/-
      1.8 ppb and a rise in PVR to 13.6 +/- 3.6 mmHg.l-1.min. Vasoconstriction with the
      thromboxane analogue U-46619 (10(-9) M) raised PVR to 31.7 +/- 6.8 mmHg.l-1.min
      but did not decrease NO levels from baseline. Subsequent addition of
      acetylcholine (10(-6)M) lowered PVR to 22.1 +/- 4.5 mmHg.l-1.min and increased
      exhaled NO to 7.0 +/- 2.0 ppb. Addition of a NO synthase inhibitor, NG-nitro-L
      arginine methyl ester (10(-5) M), to four lungs caused a rise in PVR to 43.0 +/-
      7.0 mmHg.l-1.min and a decrease in NO to 1.5 +/- 1.0 ppb. Addition of autologous
      blood to the perfusate of four lungs caused no change in PVR from baseline but
      decreased exhaled NO to 2.7 +/- 0.5 ppb.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713848
TI  - Hypoxic effects on exercise-induced diaphragmatic fatigue in normal healthy
      humans.
AB  - We examined the effects of hypoxia on exercise-induced diaphragmatic fatigue.
      Eleven subjects with a mean maximal O2 uptake of 52.4 +/- 0.7 ml.kg-1.min-1
      completed one normoxic (arterial O2 saturation 96-94%) and one hypoxic
      (inspiratory O2 fraction = 0.15; arterial O2 saturation 83-77%) exercise test at
      85% maximal O2 uptake to exhaustion on separate days. Supramaximal bilateral
      phrenic nerve stimulation (BPNS) was used to determine the pressure generation of
      the diaphragm pre- and postexercise at 1, 10, and 20 Hz. There was increased flow
      limitation during hypoxic vs. normoxic exercise. There was a decrease in hypoxic
      exercise time (normoxic 24.9 +/- 0.7 min vs. hypoxic 15.8 +/- 0.8 min; P < 0.05).
      After exercise the BPNS transdiaphragmatic pressure (Pdi) was significantly
      reduced at 1 and 10 Hz after both exercise tests. The BPNS Pdi was recovered to
      control values by 60 min postnormoxic exercise but was still reduced 90 min
      posthypoxic exercise. The mean percent fall in the stimulated BPNS Pdi was
      similar (normoxic -24.8 +/- 4.7%; hypoxic -18.8 +/- 3.0%) after both exercise
      conditions. Experiencing the same amount of diaphragm fatigue in a shorter time
      period in hypoxic exercise may have been due to 1) the increased expiratory flow
      limitation and diaphragmatic muscle work, 2) decreased O2 transport to the
      diaphragm, and/or 3) increased levels of circulating metabolites.

PMID- 7713847
TI  - Exercise training attenuates the reduction in myocardial GLUT-4 in diabetic rats.
AB  - The purpose of this study was to determine the interactive effects of 10-12 wk of
      streptozotocin-induced diabetes (65 mg/kg) and moderate-intensity exercise
      training on total myocardial GLUT-4 and GLUT-1 proteins. Sprague-Dawley rats (n =
      52) were randomly divided into sedentary control (SC), exercise-trained control
      (ETC), sedentary diabetic (SD), and exercise-trained control (ETD) groups.
      Diabetes (SD), and exercise-trained diabetic (ETD) groups. Diabetes resulted in a
      70% reduction in myocardial GLUT-4 (28.3+/- 3.1 and 94.6 +/- 3.4% for SD and SC,
      respectively; P < 0.0001) and an 18.5% decrease in GLUT-1 (62.5 +/- 4.7 and 76.8
      +/- 4.5% for SD and SC, respectively; P = 0.06). Exercise training increased
      citrate synthase activity in the medial and long heads of the triceps brachii in
      both groups (P < 0.001). Fasting blood glucose improved with training in diabetic
      animals (348 +/- 27 and 569 +/- 28 mg/dl for ETD and SD, respectively; P < 0.05).
      The diabetes-induced reduction in GLUT-4 was attenuated with exercise training
      (46.8 +/- 9.3% for ETD; P < 0.02 compared with SD). In contrast, training
      resulted in a further 25% decrease compared with SD in GLUT-1 in ETD (46.8 +/-
      9.3%; P < 0.03 compared with SD). Exercise training had no effect on either GLUT
      4 (87.2 +/- 4.0%) or GLUT-1 (75.4 +/- 5.1%) in ETC. GLUT-4 inversely correlated
      (r = -0.81; P < or = 0.001) with fasting blood glucose. In conclusion, diabetes
      resulted in a 70% reduction in myocardial GLUT-4 and an 18% decrease in GLUT
      1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713849
TI  - Arterial and arteriolar contributions to skeletal muscle functional hyperemia in
      spontaneously hypertensive rats.
AB  - During contractions of the spinotrapezius muscle in spontaneously hypertensive
      rats (SHR), arteriolar dilation is of normal magnitude but tissue PO2 is
      significantly depressed relative to normotensive [Wistar-Kyoto (WKY)] rats. This
      study examined the possibility that this low PO2 results from suppressed dilation
      of the upstream arterial feed vessels and a limitation of muscle blood flow.
      Contraction-induced changes in vascular resistances (R) and conductances (G) were
      calculated for upstream (Rup, Gup), microvascular (Rst, Gst), and downstream
      (Rdown, Gdown) vascular segments from measurements of pressure and flow in the
      rostral feed artery and vein. Feed arteries were smaller in SHR than in WKY rats
      at rest and after contractions (rest, 63.0 +/- 2.6 vs. 86.0 +/- 4.8 microns; 2 Hz
      84.0 +/- 4.5 vs. 111.0 +/- 7.3 microns; 8 Hz, 130.0 +/- 5.9 vs. 144.0 +/- 7.1
      microns). However, relative increases [times control (xCT)] in diameter and flow
      were greater in SHR (8 Hz diam, 2.080 +/- 0.072 vs. 1.690 +/- 0.042 xCT; 8 Hz
      flow, 15.700 +/- 2.057 vs. 8.170 +/- 0.752 xCT). In both groups, Rup and Rst
      decreased 60-70 and 85-90% after 2- and 8-Hz contractions, respectively. However,
      segmental vascular conductances increased more in SHR than in WKY rats (8 Hz:
      Gup, 18.50 +/- 3.76 vs. 8.00 +/- 1.26 xCT; Gst, 19.90 +/- 3.73 vs. 10.10 +/- 0.96
      xCT; Gdown, 8.80 +/- 1.70 vs. 5.50 +/- 0.88 xCT). Therefore, upstream arterial
      dilation is not suppressed during muscle contractions in SHR, and deficits in
      muscle blood flow and oxygen delivery cannot account for the abnormally low
      tissue PO2 observed during muscle contractions in SHR.

PMID- 7713850
TI  - Treatment of depression in patients with diabetes mellitus.
AB  - BACKGROUND: Depression occurs frequently in patients with diabetes mellitus.
      Little has been published on the epidemiology, biochemistry, and treatment of
      depression in diabetic patients. METHOD: We searched MEDLINE for literature from
      January 1966 to July 1993 and cross-referenced the terms diabetes, glucose,
      hyperglycemia, or hypoglycemia, with each of the following: antidepressants,
      monoamine oxidase inhibitors, tricyclic antidepressants, fluoxetine, paroxetine,
      sertraline, and bupropion. The results reviewed were 20 papers on epidemiology,
      15 papers on neurochemicals and glucose control, and 28 papers on antidepressants
      and factors of importance to diabetics. Additional papers were selected from the
      reference lists of the retrieved articles. RESULTS: The prevalence of depression
      in diabetics varies from 8.5% to 27.3%. Severity of depression correlates
      strongly with many symptoms of diabetes mellitus. The hydrazine monoamine oxidase
      inhibitors (MAOIs), e.g., phenelzine, potentiate animal models of hypoglycemia
      due to direct influence on gluconeogenesis secondary to the hydrazine structure,
      not to MAOI considerations. Dopamine and norepinephrine influences in these
      models appear to be hyperglycemic. Serotonergic influences, in the presence of
      MAOIs, which decrease serotonin metabolism, are in contrast hypoglycemic.
      Clinically, MAOI use is limited by the possible severity of the induced
      hypoglycemia, induced weight gain, and required diets. The tricyclic
      antidepressants may lead to hyperglycemia, to an increase in carbohydrate craving
      (from 86% to 200%), and impaired memory. Serotonin selective reuptake inhibitors
      (SSRIs) may be hypoglycemic (causing as much as a 30% decrease in fasting plasma
      glucose) and anorectic (causing an approximately 2-lb decrease), while possibly
      improving alertness. CONCLUSION: Depression is frequent among diabetic patients
      and impairs diabetic management. To maximize response of both depression and
      diabetic disorder, one should consider the SSRIs in preference over the TCAs.

PMID- 7713851
TI  - Sexual dysfunction in male schizophrenic patients.
AB  - BACKGROUND: Neuroleptic treatment in schizophrenic patients is associated with
      sexual dysfunction. However, it is not clear to what extent the psychiatric
      disorder and/or the pharmacologic treatment are responsible for the sexual
      impairment. The aim of the present study was to evaluate the sexual function of
      untreated and treated male schizophrenic patients in comparison with healthy
      subjects. METHOD: Participants included 122 male subjects: 20 drug-free
      schizophrenic patients, 51 neuroleptic-treated (depot form) schizophrenic
      patients, and 51 normal controls. A detailed structured interview was used to
      quantitatively and qualitatively assess sexual function. RESULTS: A high
      frequency of sexual dysfunction was reported by both schizophrenic groups of
      patients. Impairments in arousal items (erection) and orgasm during sex were
      reported mainly by the treated patients. Desire parameters were reduced in both
      schizophrenic groups, but reduction in the frequency of sexual thoughts was
      confined to the untreated one. The schizophrenic patients were more involved in
      masturbatory activity in comparison with the control subjects. Treated patients
      disclosed dissatisfaction with their sexual function. CONCLUSION: Untreated
      schizophrenic patients exhibit decreased sexual desire. Neuroleptic treatment is
      associated with restoration of sexual desire yet it entails erectile, orgasmic,
      and sexual satisfaction problems. Clinicians' awareness and open discussion of
      sexual problems with patients may improve comprehension and compliance.

PMID- 7713852
TI  - A double-blind, randomized study to provide safety information on switching
      fluoxetine-treated patients to paroxetine without an intervening washout period.
AB  - BACKGROUND: The long elimination half-lives of fluoxetine and norfluoxetine, the
      active metabolite of fluoxetine, are of potential consequence when alternative
      antidepressant agents are introduced after the termination of fluoxetine therapy.
      It is not known whether paroxetine, an antidepressant agent in the same
      pharmacologic class as fluoxetine, can be substituted for fluoxetine without the
      need for an intervening washout period. The objective of this trial was to assess
      the tolerability of an immediate switch from fluoxetine to paroxetine therapy.
      METHOD: Patients who were treated for moderate to moderately severe major
      depressive disorder (DSM-III-R 296.2 or 296.3) with a stable dose of fluoxetine
      for a minimum of 6 weeks' duration were randomized in a double-blind fashion to
      one of two treatment groups. One group (N = 123) was started on 20 mg of
      paroxetine daily the morning after their last dose of fluoxetine, and the other
      group (N = 119) was started on 20 mg of paroxetine daily following a 2-week
      placebo-washout period. Patient visits were scheduled at weekly intervals for a
      total of 4 weeks. Adverse experience monitoring was conducted at each visit.
      RESULTS: There was no difference in the proportion of patients who discontinued
      prematurely from the trial due to an adverse experience. Eight patients in the
      immediate-switch group and 6 patients in the placebo-washout group withdrew from
      the trial in response to an adverse experience (p = .63, chi-square). The overall
      profile of adverse experiences was similar in the two treatment groups over the 4
      week period. The incidence of adverse experiences in the first 2 weeks following
      the initiation of paroxetine was generally lower in the group with the
      intervening 2-week placebo-washout period. CONCLUSION: The immediate switch from
      fluoxetine to paroxetine was as well tolerated as the switch to paroxetine after
      a 2-week placebo-washout period.

PMID- 7713853
TI  - The dual diagnosis of attention-deficit/hyperactivity disorder and substance
      abuse: case reports and literature review.
AB  - BACKGROUND: It is now recognized that attention-deficit/hyperactivity disorder
      (ADHD) may persist into adulthood. A number of studies have found an association
      between ADHD and substance abuse. This article describes three adult patients
      with both ADHD and substance abuse who were treated successfully with
      psychostimulants. A review of the relevant literature is included. METHOD: The
      patients were drawn from a university-based referral center for adults with ADHD.
      Evaluations for ADHD and substance abuse were completed. Medical therapy and
      follow-up were completed by the first author. RESULTS: All of the patients
      responded to psychostimulants and have remained abstinent from alcohol and other
      drugs for the past 2 to 3 years. CONCLUSION: This case series and review of the
      literature suggest that specific treatment for ADHD with psychostimulants is
      feasible in patients who also have substance abuse. Future studies should
      evaluate the prevalence of this "dual diagnosis" and the efficacy of differing
      management strategies.

PMID- 7713854
TI  - Medical histories and psychological profiles of middle-aged women with and
      without self-reported illness from environmental chemicals.
AB  - BACKGROUND: Cacosmia, which is a predictor of cognitive deficits in industrial
      samples, is a core symptom of several controversial syndromes. Previous studies
      of cacosmic populations have considered only psychiatric but not medical or
      family histories of identified patients. METHOD: This questionnaire survey study
      examined subjective characteristics of illness from chemical odors, sensitivity
      to chemicals, psychological and stress profiles, and medical, psychiatric, and
      family health histories of 28 middle-aged women with cacosmia in self-reported
      poor health attributed to chemicals (MCS), 17 controls with cacosmia in good
      health, and 20 normal controls without cacosmia in good health. RESULTS: Those
      with MCS rated themselves in significantly poorer overall health with higher
      Pennebaker symptom scores, a larger number of chemical triggers, and greater
      frequency of illness from chemicals than the other two groups, even after
      controlling for variables on which the groups differed (i.e., education, Symptom
      Checklist-90 [revised] somatization, obsessive-compulsiveness, depression,
      anxiety, phobic anxiety, psychoticism, Barsky Somatic Symptom Amplification, and
      Cheek-Buss shyness). Despite increased levels of affective distress, those with
      MCS reported the greatest intolerance for alcohol and the lowest alcohol
      consumption. CONCLUSION: The data suggest that women with MCS report increased
      disability, multiple medical diagnoses including inflammatory and gynecologic
      dysfunctions, and psychological distress. The data are consistent descriptively
      with the phenomenology of somatization disorder. However, the persisting
      significance of group health rating differences after controlling for
      psychological variables, the lack of differences in life stress ratings between
      those with MCS and healthy cacosmics, the later age at onset (60% after age 30
      years), and the lack of excess family psychiatric histories in this sample of
      women with MCS suggest a potential role for an organic factor in the evolution of
      poor health in certain cacosmics.

PMID- 7713856
TI  - No difference in the effect of biperiden and amantadine on parkinsonian- and
      tardive dyskinesia-type involuntary movements: a double-blind crossover, placebo
      controlled study in medicated chronic schizophrenic patients.
AB  - BACKGROUND: There are few objective guidelines for the clinician in the choice of
      antiparkinsonian drugs, even though these drugs are a heterogeneous group. We
      compared the effect of biperiden (M1 selective anticholinergic) and amantadine
      (dopaminergic) on neuroleptic-induced parkinsonian extrapyramidal symptoms (EPS)
      and tardive dyskinesia (TD)-type involuntary movements. METHOD: Thirty-two
      schizophrenic (DSM-III-R) inpatients on long-term stable antipsychotic and
      trihexyphenidyl treatment entered the study. Antipsychotics were kept constant,
      but trihexyphenidyl was replaced by placebo under single-blind conditions for 1
      week, and the the patients were randomly assigned to either amantadine 100 mg
      b.i.d. or biperiden 2 mg b.i.d. treatment under double-blind conditions for 2
      weeks. After a second 1-week placebo period, the test drugs were crossed over
      under double-blind conditions. Assessments of tardive dyskinesia (Abnormal
      Involuntary Movement Scale [AIMS]) and of parkinsonian extrapyramidal side
      effects (Simpson-Angus Neurologic Rating Scale) were made pretreatment and
      posttreatment. RESULTS: Twenty-six patients completed all study procedures.
      Amantadine and biperiden were equally effective in relieving neuroleptic-induced
      EPS and did not exacerbate TD-type movements. AIMS scores during treatment were
      significantly lower than during placebo period. The findings were similar in
      patients with diagnosable TD. CONCLUSION: Amantadine and biperiden have similar
      effects on neuroleptic-induced EPS and TD and may ameliorate mild TD.

PMID- 7713855
TI  - Bacillary angiomatosis: a treatable cause of acute psychiatric symptoms in human
      immunodeficiency virus infection.
AB  - BACKGROUND: Bacillary angiomatosis is a systemic infection that has been most
      commonly reported in the setting of immunosuppression, especially human
      immunodeficiency virus (HIV) disease. METHOD: We report two patients who had
      bacillary angiomatosis who presented with psychiatric symptoms. RESULTS: The
      first patient presented with marked exacerbation of previous depressive disease.
      The second patient presented with new psychotic symptoms. In both cases
      psychiatric symptoms did not resolve until antibiotic treatment was given.
      CONCLUSION: Our report expands the clinical spectrum of bacillary angiomatosis
      and identifies a new cause of treatable psychiatric disease in HIV-infected
      persons.

PMID- 7713858
TI  - Fluoxetine-clomipramine interaction.

PMID- 7713857
TI  - Delusional misidentification of the self associated with nondominant cerebral
      pathology.

PMID- 7713859
TI  - Haloperidol decanoate: injection site reactions.

PMID- 7713860
TI  - Added amantadine may diminish tardive dyskinesia in patients requiring continued
      neuroleptics.

PMID- 7713861
TI  - Kleptomania, compulsive buying, and binge-eating disorder.
AB  - Although recognized since at least the early 19th century, kleptomania,
      compulsive buying, and binge-eating disorder are poorly understood conditions
      that have received little systematic study. In this article, we review the
      available studies of these three conditions, which suggest that they are more
      common than realized, occur more frequently in women than in men, cause
      significant morbidity, are related to other psychiatric disorders (especially to
      one another, impulse control disorders, obsessive-compulsive disorder, and mood
      disorders), and often respond to available psychopharmacologic and psychological
      treatments. We hypothesize that these three conditions might best be viewed as
      impulse control disorders that belong to an extended family of compulsive
      impulsive spectrum disorders. The compulsive-impulsive spectrum disorders may, in
      turn, belong to the larger family of affective spectrum disorder.

PMID- 7713862
TI  - Trichotillomania and obsessive-compulsive disorder.
AB  - Trichotillomania, a disorder characterized by repetitive hair pulling, has been
      only recently systemically investigated. Such research was encouraged by data
      that showed obsessive-compulsive disorder, which is also characterized by ritual
      behaviors, responds selectively to serotonin reuptake inhibitors. In this review,
      we consider similarities and contrasts in the diagnosis, demographics,
      phenomenology, neurochemistry, neuropsychiatry, and treatment of trichotillomania
      and obsessive-compulsive disorder. We argue that a view of trichotillomania as an
      obsessive-compulsive spectrum disorder that may involve disturbances in grooming
      behaviors comprises a useful clinical and research heuristic. Nevertheless, there
      may also be important differences between the two disorders; in particular,
      trichotillomania has a number of characteristics in common with impulsive
      disorders. Further empirical investigation is necessary to determine the nature
      of these complex disorders and their relationship to one another.

PMID- 7713863
TI  - Obsessive-compulsive spectrum disorders.

PMID- 7713864
TI  - Depersonalization disorder and self-injurious behavior.
AB  - Depersonalization is a subjective sense of unreality regarding various aspects of
      the self, experienced as disconnectedness from one's own body, mentations,
      feelings, or actions. When episodes of depersonalization are recurrent or
      persistent and lead to distress or dysfunction, the diagnosis of
      depersonalization disorder is made. Certain similarities in phenomenology,
      comorbidity, neurochemistry, and treatment response suggest a relationship to the
      obsessive-compulsive spectrum. However, depersonalization is a very poorly
      studied condition, and any conclusions must be viewed tentatively. Self-injurious
      behaviors are defined as intentionally self-inflicted bodily injuries without
      lethal intent. Basic categories are briefly described. Subsequently, the
      phenomenology and biology of both impulsive and compulsive self-injurious
      behaviors, and their relationship to the obsessive-compulsive spectrum, are
      discussed.

PMID- 7713865
TI  - Body dysmorphic disorder: an obsessive-compulsive spectrum disorder, a form of
      affective spectrum disorder, or both?
AB  - Over the past century, body dysmorphic disorder (BDD), a preoccupation with an
      imagined or slight defect in appearance, has been hypothesized to be related to
      obsessive-compulsive disorder (OCD). More recently, BDD has also been
      hypothesized to be a form of affective spectrum disorder. Affective spectrum
      disorder refers to a family of disorders postulated to have a common
      pathophysiologic abnormality. This grouping of disorders has been identified on
      the basis of their response to pharmacologic treatments and is supported by
      comorbidity and family studies. Available data suggest that BDD should be
      considered a candidate form of affective spectrum disorder--a disorder that may
      eventually be demonstrated to belong to this family of disorders. Available data
      also strongly support the hypothesis that BDD is an obsessive-compulsive spectrum
      disorder. Because OCD itself has been hypothesized to be an affective spectrum
      disorder, BDD may be more narrowly conceptualized as an obsessive-compulsive
      spectrum disorder and more broadly as a candidate form of affective spectrum
      disorder.

PMID- 7713867
TI  - Mechanisms of antigenic variation in Borrelia hermsii and African trypanosomes.

PMID- 7713866
TI  - Body dysmorphic disorder, pathological gambling, and sexual compulsions.
AB  - This article focuses on body dysmorphic disorder (BDD), pathological gambling,
      and sexual compulsions within the realm of obsessive-compulsive spectrum
      disorders. These three disorders affect sizable numbers of the population, have
      an early age at onset and chronic courses, and seem to have a preferential
      response to serotonin reuptake inhibitors (SRIs). They also have a high
      comorbidity with obsessive-compulsive disorder, depression, and other impulse
      control disorders. BDD patients lie more toward the compulsive/risk-aversive end
      of the dimensional model of obsessive-compulsive spectrum disorder and often have
      poor insight. Pathological gambling patients lie more toward the
      impulsivity/novelty-seeking end of the OCD spectrum and often have features of
      inattention. Sexual obsessions and/or compulsions encompass a heterogeneous group
      of disorders, as exhibited by differential response to SRIs within this group.
      These three disorders fall within a new and evolving field that requires further
      investigation and reconceptualization. This concept may have far-reaching
      consequences and yield more significant treatment outcomes.

PMID- 7713868
TI  - Platelet-activating factor stimulates transcription of the heparin-binding
      epidermal growth factor-like growth factor in monocytes. Correlation with an
      increased kappa B binding activity.
AB  - Human peripheral blood monocytes responded to stimulation of platelet-activating
      factor (PAF) with up-regulation of the transcript for heparin-binding epidermal
      growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth
      muscle cells. This function of PAF was observed at nanomolar concentrations of
      the ligand, starting at 30 min after stimulation. The PAF-induced up-regulation
      of HB-EGF mRNA was accompanied by an increase in kappa B binding activity. These
      functions of PAF appeared to be mediated through the cell surface PAF receptors,
      as two PAF receptor antagonists, WEB 2086 and L-659,989, blocked both the up
      regulation of HB-EGF mRNA and kappa B binding activity induced by PAF. The
      antagonists, however, had no effect on phorbol ester-induced up-regulation of HB
      EGF mRNA and kappa B binding activity. Pretreatment of monocytes with pertussis
      toxin inhibited these functions of PAF, whereas cholera toxin had no inhibitory
      effect. Pyrrolidine dithiocarbamate, an inhibitor for NF-kappa B activation,
      markedly reduced PAF-stimulated kappa B binding activity as well as up-regulation
      of HB-EGF mRNA. These results suggest a potential role of PAF in HB-EGF
      expression and provide evidence that this stimulation may occur through increased
      kappa B binding activity.

PMID- 7713869
TI  - Adenovirus E1A represses cardiac gene transcription and reactivates DNA synthesis
      in ventricular myocytes, via alternative pocket protein- and p300-binding
      domains.
AB  - To examine the potential impact of disrupting "pocket" protein function on
      cardiac differentiation and growth, we introduced 12 S E1A genes into neonatal
      ventricular myocytes, by adenoviral gene transfer. In the absence of E1B, E1A was
      cytotoxic, with features typical of apoptosis. In the presence of E1B, E1A
      preferentially inhibited transcription of cardiac-restricted alpha-actin
      promoters, and reactivated DNA synthesis in cardiac myocytes, without cell death.
      Mutations that abrogate known activities of the amino terminus of E1A, versus
      conserved region 2, demonstrate that the "pocket" protein- and p300-binding
      domains each suffice, in the absence of the other, for transcriptional repression
      and re-entry into S phase.

PMID- 7713870
TI  - Purification and characterization of a vasoactive intestinal polypeptide
      degrading endoprotease from porcine antral mucosal membranes.
AB  - A neutral endoprotease was isolated from porcine antral mucosa and purified to
      homogeneity as examined by SDS-polyacrylamide gel electrophoresis (PAGE).
      Throughout the purification, t-butyloxycarbonyl-Arg-Val-Arg-Arg-4- methylcoumaryl
      7-amide (MCA) was used as a substrate, which was found to be hydrolyzed
      specifically by the enzyme at the Arg-Arg bond. Unexpectedly, however, the enzyme
      was also found to hydrolyze vasoactive intestinal polypeptide (VIP) fairly
      specifically and more efficiently when various neuropeptides and related peptides
      were examined as substrates. It could degrade VIP by cleaving three peptide bonds
      not containing an arginine residue(s) with Km = 7.7 x 10(-6) M and kcat/Km = 7.4
      x 10(6) M-1 s-1 (at pH 7.6 in the presence of 0.1% Lubrol PX), whereas only
      secretin, substance P, and a few others were hydrolyzed at much slower rates
      among the various peptides examined. Both activities toward the MCA substrate and
      VIP behaved in parallel throughout the purification procedures and showed
      essentially the same pH optimum and susceptibility toward various inhibitors and
      detergents. Therefore, both activities are thought to be due to the same enzyme.
      This endoprotease required 0.001% or a higher concentration of a detergent such
      as Lubrol PX or Triton X-100 for its maximal activity. Its optimum pH was about
      7.5 and the molecular weight was estimated to be approximately 37,000 by SDS
      PAGE. This enzyme was strongly inhibited by serine protease inhibitors such as
      diisopropyl-fluorophosphate and phenylmethanesulfonyl fluoride. It was also
      inhibited by p-chloromercuribenzoic acid, but not by some other cysteine protease
      inhibitors. Therefore, the enzyme appears to be most likely a kind of serine
      protease although its possibility as a cysteine protease cannot be completely
      excluded. Analysis of its cleavage specificity toward various oligopeptides
      indicated the possibility that the protease might recognize a specific amino acid
      sequence(s) and/or conformation in the vicinity of the cleavage site of the
      target peptide. Various characteristics of the endoprotease suggest that it is a
      novel membrane-bound neuropeptide-degrading endoprotease fairly specific for VIP.

PMID- 7713871
TI  - Mechanism of inhibition of xanthine oxidase with a new tight binding inhibitor.
AB  - The mechanism of inhibition of milk xanthine oxidase and xanthine dehydrogenase
      by the tight binding inhibitor, sodium-8-(3-methoxy-4
      phenylsulfinylphenyl)pyrazolo[1,5-a]-1,3,5- triazine-4-olate monohydrate (BOF
      4272), was studied after separation of the two isomers. The steady state kinetics
      showed that the inhibition by these compounds was a mixed type. One of the
      isomers had a Ki value of 1.2 x 10(-9) M and a Ki' value of 9 x 10(-9) M, while
      the other isomer had a Ki value of 3 x 10(-7) M and a Ki' value of 9 x 10(-6) M.
      Spectral changes were not observed by mixing either the oxidized or reduced form
      of the enzyme with BOF-4272. The stopped-flow study and the effects of BOF-4272
      on various substrates showed that BOF-4272 bound to the xanthine binding site of
      the enzyme. Kd values of the enzyme and one of the isomers, which has a higher
      affinity for the enzyme, were also found to be 2 x 10(-9) M for the active form
      of the enzyme and 7 x 10(-9) M for the desulfo-form using fluorometric titration,
      and the binding has stoichiometry of 1:1. The inhibitor could not bind to the
      enzyme when the enzyme was previously treated with oxipurinol.

PMID- 7713872
TI  - Glutaredoxin accelerates glutathione-dependent folding of reduced ribonuclease A
      together with protein disulfide-isomerase.
AB  - Glutaredoxin (Grx) contains a redox-active disulfide and catalyzes thiol
      disulfide interchange reactions with specificity for GSH. The dithiol form of Grx
      reduces mixed disulfides involving GSH or protein disulfides. During oxidative
      refolding of 8 microM reduced and denatured ribonuclease RNase-(SH)8 in a redox
      buffer of 1 mM GSH and 0.2 mM GSSG to yield native RNase-(S2)4, a large number of
      GSH-mixed disulfide species are formed. A lag phase that precedes formation of
      folded active RNase at a steady-state rate was shortened or eliminated by the
      presence of a catalytic concentration (0.5 microM) of Escherichia coli Grx
      together with protein disulfide-isomerase (PDI), its procaryotic equivalent E.
      coli DsbA, or the PDI analogue the E. coli thioredoxin mutant protein P34H. A
      mutant Grx in which one of the active site cysteine residues (Cys-11 and Cys-14)
      had been replaced by serine, C14S Grx, had similar effect compared with its wild
      type counterpart. This demonstrated that Grx acted by a monothiol mechanism
      involving only Cys-11 and that RNase-S-SG-mixed disulfides were the substrates.
      Grx displayed synergistic activity together with PDI only in GSH/GSSG redox
      buffers with sufficiently low redox potential (E'0 of -208 or -181 mV) to allow
      reduction of the active site of Grx. In refolding systems that do not depend on
      glutathione, like cystamine/cysteamine or in the presence of selenite (SeO3(2-)),
      no synergistic activity of Grx was observed with PDI. We conclude that Grx acts
      by reducing mixed disulfides between GSH and RNase that are rate-limiting in
      enzyme-catalyzed refolding.

PMID- 7713873
TI  - A high affinity digoxin-binding protein displayed on M13 is functionally
      identical to the native protein.
AB  - Phage display of peptides and proteins has successfully been employed to produce
      binding molecules of altered affinity. Little is known, however, regarding the
      impact on affinity measurements of phage-displayed molecules compared to their
      native freely soluble configuration. That identical affinities can be obtained
      was shown by Scatchard analysis of the native antibody, its single chain
      derivative (scFv), and its phage-displayed single chain counterpart for the
      ligand digoxin. No significant difference, within one standard deviation, was
      detected in affinity for digoxin when the phage-displayed scFv was compared to
      either its soluble scFv form or the purified antibody. In addition, no change in
      binding specificity was detected, within two standard deviations, when the
      binding proteins were challenged with two commonly cross-reactive compounds
      (dihydrodigoxin and digitoxin). That phage-display can be employed for molecules
      having high binding affinities (Kd of 6 x 10(-11) M) is also shown.

PMID- 7713874
TI  - In vitro motility analysis of actin-tropomyosin regulation by troponin and
      calcium. The thin filament is switched as a single cooperative unit.
AB  - In striated muscles, contractility is controlled by Ca2+ binding to the
      regulatory protein complex troponin, which is a component of the thin filaments.
      Troponin is an allosteric inhibitor acting on tropomyosin to switch the thin
      filament between "on" and "off" states. We have used an in vitro motility assay
      to examine troponin regulation of individual actin-tropomyosin filaments moving
      over immobilized skeletal muscle heavy meromyosin. The most striking observation
      is that the actintropomyosin filament appears to be regulated as a single unit.
      At pCa 9.0, addition of up to 4 nM troponin causes the proportion of filaments
      motile to decrease from > 85% to 20% with no dissociation of the filaments from
      the heavy meromyosin surface or change in velocity. Increasing Ca2+ concentration
      causes the filaments to be switched back on with half-maximal increase in the
      proportion of filaments motile at pCa 5.8-6.0 and a modest increase in filament
      velocity. This is an "all or none" process in which an entire filament, up to 15
      microns long, switches rapidly as a single cooperative unit. Thus, the effect of
      Ca2+ upon the thin filament is to recruit motile filaments.

PMID- 7713876
TI  - Singlet oxygen generation from the reaction of ozone with plant leaves.
AB  - Aqueous extracts of the intercellular fluid from Sedum album L. leaves generated
      singlet oxygen chemiluminescence at 1270 nm when exposed to a nitrogen gas stream
      containing ozone at 21 +/- 2 ppm. The concentration of ascorbic acid in the
      intercellular fluid extracts was 310 +/- 40 microM. The intensity of the singlet
      oxygen chemiluminescence from the intercellular fluid extracts was comparable
      with the chemiluminescence from a control solution containing 300 microM ascorbic
      acid. The intensity of the singlet oxygen emission from intercellular fluid
      treated with ascorbate oxidase was 0.19 +/- 0.07 of the intensity of the singlet
      oxygen chemiluminescence from untreated samples of intercellular fluid extract.
      The simplest explanation for the effect of ascorbate oxidase is that ascorbic
      acid is the major ozone target generating singlet oxygen. Much weaker singlet
      oxygen chemiluminescence was detected at 1270 nm when intact S. album L. plant
      tips were exposed to a nitrogen gas stream containing ozone at 22 +/- 5 ppm.
      Various explanations for the relatively low intensity of the singlet oxygen
      chemiluminescence from intact S. album L. plant tips are discussed.

PMID- 7713875
TI  - Distinguishing between folate receptor-alpha-mediated transport and reduced
      folate carrier-mediated transport in L1210 leukemia cells.
AB  - L1210 leukemia cells transport reduced folates and methotrexate via a well
      defined reduced folate carrier system and, in the absence of low folate selective
      pressure, do not express an alternate endocytotic route mediated by cell surface
      folate receptors. This laboratory previously described an L1210 leukemia cell
      line, MTXrA, with acquired resistance to methotrexate (MTX) due to the loss of
      mobility of the reduced folate carrier. We now report on the transfection of
      MTXrA with a cDNA encoding the murine homolog of the human folate receptor
      isoform of KB cells to produce MTXrA-TF1, which constitutively expresses high
      levels of FR-alpha. MTXrA-TF1 and L1210 cells were utilized to compare transport
      of methotrexate mediated by FR-alpha and the reduced folate carrier,
      respectively. Methotrexate influx in the two lines was similar when the
      extracellular level was 0.1 microM, but as the methotrexate concentration
      increased, influx via the reduced folate carrier increased in comparison to
      influx mediated by FR-alpha. Transport kinetics indicated both a approximately 20
      fold lower influx Kb and Vmax for MTXrA-TF1 as compared to L1210 cells. The two
      cell lines exhibited distinct influx properties. Methotrexate influx in MTXrA-TF1
      was markedly inhibited by 50 nM folic acid and metabolic poisons. In L1210 cells,
      1.0 microM folic acid did not affect MTX influx, and metabolic poisons either had
      no effect on or increased methotrexate influx. Removal of extracellular chloride
      markedly inhibited transport in MTXrA-TF1 but stimulated influx in L1210 cells.
      When the pH was decreased to 6.2, methotrexate influx was not altered in MTXrA
      TF1 but was reduced in L1210 cells. Probenecid and sulfobromophthalein inhibit
      methotrexate influx in both L1210 and MTXrA-TF1 cell lines; however, inhibition
      in MTXrA-TF1 could be accounted for on the basis of inhibition of methotrexate
      binding to FR-alpha. The data indicate that the reduced folate carrier and FR
      alpha function independently and exhibit distinct properties. FR-alpha expressed
      at sufficient levels can mediate influx of MTX and folates into cells at rates
      comparable to the reduced folate carrier and hence has pharmacologic and
      physiologic importance.

PMID- 7713877
TI  - The mechanism of electron donation to molecular oxygen by phagocytic cytochrome
      b558.
AB  - Phagocytic cytochrome b558 is a unique heme-containing enzyme, which catalyzes
      one electron reduction of molecular oxygen to produce a superoxide anion with a
      six-coordinated heme iron. To clarify the mechanism of the superoxide production,
      we have analyzed oxidation-reduction kinetics of cytochrome b558 purified from
      porcine neutrophils by stopped-flow and rapid-scanning spectroscopy. Reduced
      cytochrome b558 was rapidly reoxidized by O2 showing spectral changes with clear
      isosbestic points, which were also observed during the reduction of ferric
      cytochrome b558 with Na2S2O4 under anaerobic conditions. The single turnover rate
      for the reaction with O2 linearly depended on the O2 concentration but was not
      affected by addition of CO. The rate of the reaction decreased with an increase
      of pH giving a pKa of 9.7. Under complete anaerobic conditions, ferrous
      cytochrome b558 was oxidized by ferricyanide at a rate faster than by O2. The
      thermodynamic analysis shows that the enthalpic energy barriers for the reactions
      of cytochrome b558 are significantly lower when compared to the autoxidation of
      native and modified myoglobins through the formation of the iron-O2 complex.
      These findings are most consistent with the electron transfer from the heme to O2
      by an outer-sphere mechanism.

PMID- 7713878
TI  - Sialyllactose-mediated cell interaction during granulosa cell differentiation.
      Identification of its binding proteins.
AB  - The present study was designed to prove the carbohydrate-binding proteins
      interacting with cell surface sialyllactosylceramide (GM3, NeuAc alpha 2-->3Gal
      beta 1-->4Glc beta 1-->1'Cer), which is highly expressed during differentiation
      of rat ovarian granulosa cells. As a specific ligand for the sialyllactose (SL)
      binding proteins on granulosa cells, we used a radioiodinated multivalent SL
      linked albumin (Alb-(SL)17). The specific association of the ligand to the
      putative proteins on the intact cells was competitively inhibited by GM3 more
      effectively than other gangliosides, sialyllactotetraosylceramide,
      sialylneolactotetraosylceramide, and several glycoproteins with N-linked
      oligosaccharides. However, the proteins had no specificity for the side chain (N
      acetyl or N-glycolyl forms) of sialic acid in GM3. Scatchard analysis of Alb
      (SL)17 binding showed high (Kd = 6.4 x 10(-10)M) and low (Kd = 3.1 x 10(-8)M)
      affinity population of binding sites. By direct binding of 125I-Alb-(SL)17 to SL
      binding proteins on Western blots, the putative proteins with molecular masses of
      35, 18, and 14 kDa were detected. The interaction of the multivalent derivative
      with these binding proteins was differently modulated by Ca2+ and Mn2+. The SL
      binding proteins occurred in immature granulosa cells and progressively decreased
      during differentiation, whereas their endogenous ligand GM3 increased. These
      results indicate that relatively low molecular weight SL-binding proteins exist
      on the surface of immature granulosa cells and that they may serve as receptor
      sites for newly synthesized GM3 during differentiation.

PMID- 7713879
TI  - CAAX geranylgeranyl transferase transfers farnesyl as efficiently as
      geranylgeranyl to RhoB.
AB  - RhoB, a small GTP-binding protein, was shown previously to contain farnesyl (C
      15) as well as geranylgeranyl (C-20) groups (Adamson, P., Marshall, C. J., Hall,
      A., and Tilbrook, P. A. (1992) J. Biol. Chem. 267, 20033-20038). The COOH
      terminal sequence of the protein is CCKVL. According to current rules of
      prenylation, the COOH-terminal leucine should render the protein a substrate for
      CAAX geranylgeranyl transferase (GGTase-1), but not for CAAX farnesyltransferase
      (FTase). To determine the mechanism of farnesylation, we prepared recombinant
      RhoB and incubated it with recombinant preparations of either FTase or GGTase-1.
      RhoB was neither farnesylated nor geranylgeranylated efficiently by FTase, but it
      was farnesylated as well as geranylgeranylated by GGTase-1. The enzyme attached
      farnesyl more efficiently than geranylgeranyl to RhoB. Neither farnesylation nor
      geranylgeranylation required the cysteine at the fifth position from the COOH
      terminus. However, replacement of the cysteine at the fourth position abolished
      attachment of both prenyl groups. We conclude that the previously observed
      farnesylation of RhoB is attributable to the FTase activity of GGTase-1. These
      data, and other accumulating data, indicate that GGTase-1 is a highly unusual
      enzyme that efficiently transfers both farnesyl and geranylgeranyl groups and
      that the choice of prenyl group is dictated by the nature of the protein
      acceptor.

PMID- 7713880
TI  - ATP-sensitive binding of a 70-kDa cytosolic protein to the glucose transporter in
      rat adipocytes.
AB  - We have identified a 70-kDa cytosolic protein (GTBP70) in rat adipocytes that
      binds to glutathione S-transferase fusion proteins corresponding to the
      cytoplasmic domains of the facilitative glucose transporter isoforms Glut1,
      Glut2, and Glut4. GTBP70 did not bind to irrelevant fusion proteins, indicating
      that the binding is specific to the glucose transporter. GTBP70 binding to the
      glucose transporter showed little isoform specificity but was significantly
      subdomain-specific; it bound to the C-terminal domain and the central loop, but
      not to the N-terminal domain of Glut4. The GTBP70 binding to Glut4 was not
      affected by the presence of 2 mM EDTA, 2.4 mM Ca2+, or 150 mM K+. The binding was
      inhibited by ATP in a dose-dependent manner, with 50% inhibition at 10 mM ATP.
      This inhibition was specific to ATP, as ADP and AMP-PCP (adenosine 5'-(beta,
      gamma-methylenetriphosphate)) were without effect. GTBP70 did not react with
      antibodies against phosphotyrosine, phosphothreonine, or phosphoserine,
      suggesting that it is not a phosphoprotein. The binding of GTBP70 to Glut4 was
      not affected by the pretreatment of adipocytes with insulin. When these
      experiments were repeated using rat hepatocyte cytosols, no ATP-sensitive 70-kDa
      protein binding to the glucose transporter fusion proteins was evident,
      suggesting that either GTBP70 expression or its function is cell-specific. These
      findings strongly suggest the possibility that GTBP70 may play a key role in
      glucose transporter regulation in insulin target cells such as adipocytes.

PMID- 7713881
TI  - Recombinant human eosinophil cationic protein. Ribonuclease activity is not
      essential for cytotoxicity.
AB  - Eosinophil cationic protein (ECP) is a toxin secreted by activated human
      eosinophils that has anti-parasitic, antibacterial, and neurotoxic activities;
      ECP also has ribonuclease activity and structural homology to other mammalian
      ribonucleases. To determine the relationship between the ribonuclease activity
      and cytotoxicity of ECP, a method for producing recombinant ECP (rECP) in a
      prokaryotic expression system was devised. Periplasmic isolates from induced
      bacterial transfectants contained enzymatically active rECP; micromolar
      concentrations of rECP were shown to be toxic for Staphylococcus aureus (strain
      502A). In contrast, recombinant eosinophil-derived neurotoxin, with 67% amino
      acid sequence identity to ECP, had little to no toxicity for S. aureus; these
      findings are analogous to those obtained with purified, granule-derived ECP and
      eosinophil-derived neurotoxin. Two single base pair mutations were introduced
      into the coding sequence of rECP (Lys38 to Arg and His128 to Asp) to convert
      ribonuclease active-site residues into non-functional counterparts. These
      mutations eliminated the ribonuclease activity of rECP but had no discernible
      effect on the antibacterial activity of this protein, demonstrating that
      ribonuclease activity and cytotoxicity are, in this case, independent functions
      of ECP.

PMID- 7713882
TI  - Glucose, other secretagogues, and nerve growth factor stimulate mitogen-activated
      protein kinase in the insulin-secreting beta-cell line, INS-1.
AB  - The signaling pathways whereby glucose and hormonal secretagogues regulate
      insulin-secretory function, gene transcription, and proliferation of pancreatic
      beta-cells are not well defined. We show that in the glucose-responsive beta-cell
      line INS-1, major secretagogue-stimulated signaling pathways converge to activate
      44-kDa mitogen-activated protein (MAP) kinase. Thus, glucose-induced insulin
      secretion was found to be associated with a small stimulatory effect on 44-kDa
      MAP kinase, which was synergistically enhanced by increased levels of
      intracellular cAMP and by the hormonal secretagogues glucagon-like peptide-1 and
      pituitary adenylate cyclase-activating polypeptide. Activation of 44-kDa MAP
      kinase by glucose was dependent on Ca2+ influx and may in part be mediated by MEK
      1, a MAP kinase kinase. Stimulation of Ca2+ influx by KCl was in itself
      sufficient to activate 44-kDa MAP kinase and MEK-1. Phorbol ester, an activator
      of protein kinase C, stimulated 44-kDa MAP kinase by both Ca(2+)-dependent and 
      independent pathways. Nerve growth factor, independently of changes in cytosolic
      Ca2+, efficiently stimulated 44-kDa MAP kinase without causing insulin release,
      indicating that activation of this kinase is not sufficient for secretion. In the
      presence of glucose, however, nerve growth factor potentiated insulin secretion.
      In INS-1 cells, activation of 44-kDa MAP kinase was partially correlated with the
      induction of early response genes junB, nur77, and zif268 but not with
      stimulation of DNA synthesis. Our findings suggest a role of 44-kDa MAP kinase in
      mediating some of the pleiotropic actions of secretagogues on the pancreatic beta
      cell.

PMID- 7713883
TI  - Sodium acts as a potassium analog on gastric H,K-ATPase.
AB  - The effects of Na+ on gastric H,K-ATPase were investigated using leaky and ion
      tight H,K-ATPase vesicles. Na+ activated the total ATPase activity in the absence
      of K+, reaching levels of 15% relative to those in the presence of K+. The Na+
      activation, which takes place at the luminal side of the membrane, depended on
      the ATP concentration and the type of buffer used. The steady-state ATP
      phosphorylation level, studied with leaky vesicles, was reduced by Na+ due to
      both activation of the dephosphorylation reaction and a shift to E2 in the
      E1<==>E2 equilibrium. By studying this equilibrium in ion-tight H,K-ATPase
      vesicles, it was found that Na+ drives the enzyme via a cytosolic site to the
      nonphosphorylating E2 conformation. No H(+)-like properties of cytosolic Na+
      could be detected. We therefore conclude that Na+ behaves like K+ rather than
      like H+ in the H,K-ATPase reaction.

PMID- 7713884
TI  - Detection by site-specific disulfide cross-linking of a conformational change in
      binding of Escherichia coli pyruvate oxidase to lipid bilayers.
AB  - Escherichia coli pyruvate oxidase, a peripheral membrane homotetrameric
      flavoprotein, exposes its C-terminal lipid binding site in the presence of
      substrate pyruvate and co-factor thiamine pyrophosphate Mg2+ and binds tightly to
      phospholipid bilayers during catalysis. Using site-specific disulfide cross
      linking, we demonstrate that disulfide cross-links are formed between C termini
      of D560C pyruvate oxidase and that the degree of cross-linking is greatly
      increased by the presence of substrate and co-factors indicating a conformational
      change that results in juxtaposition of two subunit C termini. The cross-linked
      oxidase is enzymatically active and remains able to associate with lipid
      micelles. These results argue strongly that lipid bilayer binding of pyruvate
      oxidase involves pairing of the C termini of two subunits.

PMID- 7713885
TI  - The C terminus of SecA is involved in both lipid binding and SecB binding.
AB  - Using C-terminal deletion mutations in secA, we localized the previously proposed
      (Breukink, E., Keller, R.C. A., and de Kruijff, B. (1993), FEBS Lett. 331, 19-24)
      second lipid binding site on SecA. Since removal of these residues completely
      abolished the property of SecA to cause aggregation of negatively charged
      phosphatidyl-glycerol vesicles, we conclude that the C-terminal 70 amino acid
      residues of SecA are involved in lipid-binding. The C-terminal 70 amino acid
      residues of SecA are important for efficient in vitro translocation of the SecB
      dependent precursor of PhoE across inverted inner membrane vesicles. Moreover, in
      vivo studies showed that this region is essential for growth. SecB and a SecB
      precursor complex were shown to inhibit the SecA-mediated lipid vesicle
      aggregation, suggesting that the overall acidic SecB protein binds at or near the
      second lipid binding site on SecA. This together with the observation that the
      SecA mutant protein lacking the C-terminal 70 residues had a strongly reduced
      ability to mediate binding of SecB-precursor complexes to inverted inner membrane
      vesicles demonstrates that the C terminus of SecA is also involved in SecB
      binding.

PMID- 7713886
TI  - Cloning and expression of the Chlamydia trachomatis gene for CTP synthetase.
AB  - A HindIII partial digest Chlamydia trachomatis L2 library in pUC19 was screened
      for the CTP synthetase gene by functional complementation in CTP synthetase
      deficient Escherichia coli JF646. A complementing clone was isolated and
      contained a recombinant plasmid (pH-1) with a 2.7-kilobase C. trachomatis DNA
      insert. The entire insert was sequenced and found to encode two complete open
      reading frames (ORFs) that overlapped by 25 bases and the start of a third ORF
      that overlapped with ORF2 by 14 bases. The derived amino acid sequence of ORFs 1
      and 2 shows 37% identity to kdsB, an E. coli gene that codes for CMP-2-keto-3
      deoxyoctulosonic acid synthetase and 48% identity to pyrG, an E. coli gene that
      codes for CTP synthetase, respectively. To obtain downstream sequence data for
      ORF3, colony hybridization screening of the HindIII chlamydial DNA library was
      used to isolate a second recombinant plasmid (pH-11) that contained a 1.7
      kilobase chlamydial DNA insert. The deduced amino acid sequence of ORF3 is not
      significantly homologous to any protein in the translated GenBank data base.
      Recombinant chlamydial CTP synthetase appears to be similar to the E. coli enzyme
      in that it is sensitive to inhibition by CTP, requires UTP, ATP, Mg2+, GTP, and
      glutamine for activity, and can also utilize ammonia as an amidogroup donor.

PMID- 7713887
TI  - The role of metabolism, cytoplasmic Ca2+, and pH-regulating exchangers in glucose
      induced rise of cytoplasmic pH in normal mouse pancreatic islets.
AB  - Intact mouse islets were loaded with 2',7'-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein to study the effects of glucose on cytoplasmic pH (pHi) in
      pancreatic B-cells. In HCO3- buffer, glucose produced a steady-state increase in
      pHi that required metabolism of the sugar and was concentration-dependent between
      0 and 10 mM (Km approximately 5 mM) before plateauing at a maximum value of
      approximately 0.2 pH units. In HEPES buffer, glucose concentrations above 7 mM
      caused an initial rise followed by a secondary decrease and an eventual return to
      about initial values. Inhibition of Ca2+ influx had little effect on the pHi
      changes produced by glucose in HCO3- medium, but unmasked an alkalinizing effect
      in HEPES buffer. Raising cytoplasmic Ca2+ by 30 mM potassium caused a larger
      acidification in HEPES than in HCO3- buffer, but a subsequent rise in glucose now
      increased pHi in both types of buffer. In the presence of 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; inhibitor of HCO3-/Cl-
      exchange), the effect of glucose on pHi in HCO3- buffer became similar to that in
      HEPES buffer. After inhibition of the Na+/H+ exchanger by dimethylamiloride,
      glucose produced a marked and sustained fall in pHi in HEPES buffer. A similar
      fall was seen in HCO3- buffer only when DIDS and dimethylamiloride were present
      together. However, if Ca2+ influx was prevented when both exchangers were
      blocked, glucose increased pHi. In conclusion, the metabolism of glucose tends to
      increase pHi in B-cells, whereas the concomitant rise in [Ca2+]i exerts an
      acidifying action. In HEPES buffer, this acidifying effect of Ca2+ is offset by
      the operation of the Na+/H+ exchanger. In physiological HCO3- buffer, the
      activity of the HCO3-/Cl- exchanger overcompensates and leads to an increase in
      pHi.

PMID- 7713888
TI  - Reaction mechanisms of homodimeric plant polyketide synthase (stilbenes and
      chalcone synthase). A single active site for the condensing reaction is
      sufficient for synthesis of stilbenes, chalcones, and 6'-deoxychalcones.
AB  - Stilbene (STS) and chalcone (CHS) synthases are homodimeric, related plant
      specific polyketide synthases. Both perform a sequential condensation of three
      acetate units to a starter residue to form a tetraketide intermediate that is
      folded to the ring systems specific to the different products. Protein cross
      linking and site-directed mutagenesis identified a subunit contact site in
      position 158, close to the active site (Cys169). This suggested that the active
      site pockets may be neighboring, possibly alternating in the condensing reactions
      rather than acting independently. This was investigated by coexpression of active
      site mutants with differently mutated, inactive proteins. With both STS and CHS,
      the heterodimers synthesized the end products, indicating that each subunit
      performed all three condensations. In co-action with a monomeric reductase, CHS
      also synthesizes 6'-deoxychalcone, but with the chalcone as second product when
      using plant preparations. The two enzymes expressed as single species in
      Escherichia coli synthesized both products, and both were also obtained with a
      CHS heterodimer containing a single active site. The results showed that 6'
      deoxychalcone synthesis required no other plant factor and that the formation of
      two products may be an intrinsic property of the interaction between dimeric CHS
      and monomeric reductase.

PMID- 7713889
TI  - Protein modification by ADP-ribose via acid-labile linkages.
AB  - As substrate for protein-mono-ADP-ribosyltransferases, NAD has been shown to be
      the donor of ADP-ribose to many different nucleophiles found in proteins. This
      post-translational modification of proteins has been implicated in the regulation
      of membrane-associated processes including signal transduction, muscle cell
      differentiation, and protein trafficking and secretion. Described here is the
      preparation and chemical characterization of low molecular weight conjugates that
      were used as models for an acetal linkage between ADP-ribose and the hydroxyl
      group of a protein acceptor such as serine, threonine, tyrosine, hydroxyproline,
      or hydroxylysine residues. Model conjugates of ADP-ribose containing an acetal
      linkage were prepared, their structures were established by NMR, and the chemical
      stability of the linkage to ADP-ribose was studied and compared to the other
      known ADP-ribosyl-amino acid linkages. The rapid release of intact ADP-ribose
      from the acetal model conjugates in 44% formic acid distinguished them chemically
      from all the other known ADP-ribosyl-amino acid modifications. Rat liver proteins
      were shown to be modified by ADP-ribose in vivo by acid-labile linkages,
      providing evidence for a new class of endogenous ADP-ribose modification of
      animal cell proteins. The amount of modification was approximately 16 pmol of ADP
      ribose per mg of total protein, and proteins modified by acid-labile linkages
      were detected in all subcellular fractions examined, suggesting that the scope of
      this modification in vivo is broad.

PMID- 7713891
TI  - Subunit assembly in the tryptophan synthase alpha 2 beta 2 complex. Stabilization
      by pyridoxal phosphate aldimine intermediates.
AB  - This work is aimed at understanding subunit assembly in the tryptophan synthase
      alpha 2 beta 2 complex and the importance of the internal aldimine between
      pyridoxal phosphate and lysine 87 of the beta 2 subunit of tryptophan synthase
      for subunit association. We utilize a mutant form of the beta 2 subunit that is
      unable to form the internal aldimine because lysine 87 is replaced by threonine
      (K87T). The K87T alpha 2 beta 2 complex is inactive in reactions catalyzed by the
      beta 2 subunit but retains activity in the reaction catalyzed by the alpha
      subunit. We find that dialysis removes pyridoxal phosphate much more rapidly from
      the K87T beta 2 subunit and alpha 2 beta 2 complex than from the wild type
      counterparts. Activity measurements, gel filtration, and subunit interchange
      experiments show that the alpha subunit dissociates more readily from the K87T
      beta 2 subunit than from the wild type beta 2 subunit. The reaction of L-serine
      to form an external aldimine with pyridoxal phosphate at the active site of the
      K87T beta 2 subunit markedly increases the affinity for the alpha subunit and
      slows removal of pyridoxal phosphate by dialysis. We propose that the external
      aldimine between L-serine and pyridoxal phosphate bridges the N-domain and the C
      domain in the K87T beta 2 subunit. This interdomain bridge may mimic the internal
      aldimine bond in the wild type beta 2 subunit and stabilize pyridoxal phosphate
      binding. The interdomain bridges formed by the internal aldimine with the wild
      type beta 2 subunit and by the external aldimine with L-serine in the K87T beta 2
      subunit may further stabilize interaction with the alpha subunit because the
      alpha/beta interaction site contains residues from both N- and C-domains of the
      beta 2 subunit.

PMID- 7713890
TI  - Cooperation of Src homology domains in the regulated binding of
      phosphatidylinositol 3-kinase. A role for the Src homology 2 domain.
AB  - Fibroblasts transformed by the v-Src oncoprotein exhibit elevated activity of the
      enzyme phosphatidylinositol 3'-kinase (PI 3-kinase), which binds to, and is
      activated by, a wide range of receptor tyrosine kinases as well as v-Src and
      transforming polyoma middle T/c-Src complexes. Here we consider the role of the v
      Src homology (SH) domains, SH3 and SH2, and the tyrosine kinase catalytic domain,
      in the stimulation of v-Src-associated PI 3-kinase activity in response to rapid
      activation of the oncoprotein. As shown by others, we find that the v-Src SH3
      domain tightly binds the PI 3-kinase p85 regulatory subunit in normal growing
      chicken embryo fibroblasts. However, we also find that in transformed cells there
      is additional efficient binding of PI 3-kinase to the v-Src SH2 domain in a
      catalytically active form. Furthermore, the binding of p85 to the SH2 domain,
      which is almost undetectable in quiescent cells, is rapidly stimulated upon
      activation of temperature-sensitive v-Src and consequent cell cycle entry,
      demonstrating that binding is a target for regulation. We also show that v-Src
      associated PI 3-kinase differs considerably from PDGF receptor-associated enzyme
      by a different mode of binding, a lack of substantial allosteric activation, and
      a dependence on the tyrosine kinase activity of v-Src. The rapidly induced
      binding and activation of PI 3-kinase thus provides sensitive regulation of
      recruitment of PI 3-kinase to its substrates and into other signaling complexes
      at the cell membrane, which involves all the Src homology domains.

PMID- 7713892
TI  - Purification of all forms of HeLa cell mitochondrial DNA and assessment of damage
      to it caused by hydrogen peroxide treatment of mitochondria or cells.
AB  - A purification scheme for mitochondrial DNA (mtDNA) was designed which maximized
      the yield of all forms of the DNA while minimizing damage to the DNA during its
      isolation. Treatment of intact mitochondria with DNase I removed nuclear DNA and
      the avoidance of phenol and the isolation by CsCl density gradients in the
      absence of ethidium bromide and subsequent detection by Southern Hydridization
      dot-blots minimized DNA damage. Four different mtDNA forms free of apparent
      nuclear DNA were obtained: closed circular (I), open circular (II), linear (III),
      and a large multimer complex (C) which were characterized by agarose gel
      electrophoresis and electron microscopy. Using this procedure, mtDNA was obtained
      from both whole cells or intact mitochondria treated with H2O2. Significant
      fragmentation was observed after treatment at 37 degrees C, but not at 0 degrees
      C, and more damage was observed when treating whole cells than isolated
      mitochondria. Very low levels of 8-hydroxydeoxyguanosine were observed in all
      cases. However, at doses of H2O2 which were just lethal, neither increased DNA
      damage nor inactivation of cytochrome c oxidase was observed.

PMID- 7713893
TI  - Comparison of the DNA binding specificity and function of v-ErbA and thyroid
      hormone receptor alpha 1.
AB  - The oncoprotein v-ErbA is a mutated version of thyroid hormone receptor alpha 1.
      Although the basis for the oncogenic action of v-ErbA is unknown, expression of
      this protein is known to inhibit thyroid hormone and retinoic acid induction of
      target genes. The DNA binding domain of v-ErbA differs from that of thyroid
      hormone receptor alpha 1 in two amino acids felt to be crucial for determining
      the specificity of DNA binding. However, the DNA binding properties of v-ErbA
      have not been examined independent of a comparison of binding to already known
      thyroid hormone response elements. In the current studies a non-biased strategy
      was used to select from a pool of random DNA those sequences that bind v-ErbA
      with high affinity. The highest affinity binding sequence was identified as the
      decamer 5'-T(A/G)AGGTCACG, which is closely related to the optimal thyroid
      hormone receptor alpha 1 binding sequence, TAAG-GTCA. Transfection studies
      demonstrate that among equal thyroid hormone responsive elements, those that
      contain the optimal v-ErbA consensus will be repressed by v-ErbA in preference to
      those that do not. These studies indicate that v-ErbA and thyroid hormone
      receptor alpha 1 regulate overlapping sets of response elements, and that all
      sequences that are highly responsive to thyroid hormone are not necessarily
      responsive to v-ErbA.

PMID- 7713894
TI  - Calcium- and pH-dependent aggregation of carboxypeptidase E.
AB  - Carboxypeptidase E (CPE) is involved with the biosynthesis of numerous peptide
      hormones and neurotransmitters. Several forms of CPE have been previously
      detected in neuroendocrine cells, including a form which is soluble at pH 5.5 (S
      CPE), a form which can be extracted from membranes with 1 M NaCl at pH 5.5 (M1
      CPE), and a form which requires both 1% Triton X-100 and 1 M NaCl for extraction
      from membranes at pH 5.5 (M2-CPE). Like other peptide processing enzymes, CPE is
      known to be sorted into peptide-containing secretory vesicles of the regulated
      pathway. One mechanism that has been proposed to be important for sorting of
      regulated pathway proteins is Ca2+ and pH-induced aggregation. CPE purified from
      bovine pituitary membranes aggregates at pH 5.5 when the concentration of CPE is
      0.3 micrograms/microliters or higher, but not when the concentration is 0.01
      microgram/microliters. Aggregation of CPE is pH-dependent, with very little
      aggregation occurring at pH 6 or above. At pH 5.0-5.5, the M2 form of CPE shows a
      greater tendency to aggregate than the other two forms. At pH 6, Ca2+
      concentrations from 1-30 mM increase the aggregation of M1- and M2-CPE, but not S
      CPE. The aggregation of M2-CPE does not explain the apparent membrane binding of
      this protein since the aggregate is solubilized by 1% Triton X-100 at pH 5.5 or
      by pH 6.0, whereas M2-CPE is not extracted from membranes under these conditions.
      Taken together, these results are consistent with a model in which the decreasing
      pH and increasing Ca2+ levels in the trans Golgi network induce the aggregation
      of CPE, which contributes to the sorting of this protein into regulated pathway
      secretory vesicles.

PMID- 7713895
TI  - Molecular and biochemical evidence for the involvement of the Asp-333-His-523
      pair in the catalytic mechanism of soluble epoxide hydrolase.
AB  - In order to investigate the involvement of amino acids in the catalytic mechanism
      of the soluble epoxide hydrolase, different mutants of the murine enzyme were
      produced using the baculovirus expression system. Our results are consistent with
      the involvement of Asp-333 and His-523 in a catalytic mechanism similar to that
      of other alpha/beta hydrolase fold enzymes. Mutation of His-263 to asparagine led
      to the loss of approximately half the specific activity compared to wild-type
      enzyme. When His-332 was replaced by asparagine, 96.7% of the specific activity
      was lost and mutation of the conserved His-523 to glutamine led to a more
      dramatic loss of 99.9% of the specific activity. No activity was detectable after
      the replacement of Asp-333 by serine. However, more than 20% of the wild-type
      activity was retained in an Asp-333-->Asn mutant produced in Spodoptera
      frugiperda cells. We purified, by affinity chromatography, the wild-type and the
      Asp-333-->Asn mutant enzymes produced in Trichoplusia ni cells. We labeled these
      enzymes by incubating them with the epoxide containing radiolabeled substrate
      juvenile hormone III (JH III). The purified Asp-333-->Asn mutant bound 6% of the
      substrate compared to the wild-type soluble epoxide hydrolase. The mutant also
      showed 8% of the specific activity of the wild-type. Preincubation of the
      purified Asp-333-->Asn mutant at 37 degrees C (pH 8), however, led to a complete
      recovery of activity and to a change of isoelectric point (pI), both of which are
      consistent with hydrolysis of Asn-333 to aspartic acid. This intramolecular
      hydrolysis of asparagine to aspartic acid may explain the activity observed in
      this mutant. Wild-type enzyme that had been radiolabeled with the substrate was
      digested with trypsin. Using reverse phase-high pressure liquid chromatography,
      we isolated four radiolabeled peptides of similar polarity. These peptides were
      not radiolabeled if the enzyme was preincubated with a selective competitive
      inhibitor of soluble epoxide hydrolase 4-fluorochalcone oxide. This strongly
      suggested that these peptides contained a catalytic amino acid. Each peptide was
      characterized with N-terminal amino acid sequencing and electrospray mass
      spectrometry. All four radiolabeled peptides contained overlapping sequences. The
      only aspartic acid present in all four peptides and conserved in all epoxide
      hydrolases was Asp-333. These peptides resulted from cleavage at different
      trypsin sites and the mass of each was consistent with the covalent linkage of
      Asp-333 to the substrate.

PMID- 7713896
TI  - A conformation-specific anti-peptide antibody to the beta-type platelet-derived
      growth factor receptor also recognizes the activated epidermal growth factor
      receptor.
AB  - Earlier we reported the generation of a conformation-specific antibody (Ab P2) to
      the beta-type platelet-derived growth factor receptor (Bishayee, S., Majumdar,
      S., Scher, C. D., and Khan, S. (1988) Mol. Cell. Biol. 8, 3696-3702). Ab P2 is
      directed to a 16-amino acid peptide (Glu-Gly-Tyr-Lys-Lys-Lys-Tyr-Gln-Gln-Val-Asp
      Glu-Glu-Phe-Leu-Arg) of the cytoplasmic domain of the receptor, and it recognizes
      the phosphorylated platelet-derived growth factor receptor but not the
      unphosphorylated receptor. We now report that Ab P2 also interacts with the
      epidermal growth factor receptor and that the recognition is specific for a
      conformation induced by phosphorylation of the receptor; however, Ab P2 is not
      directed to phosphotyrosine. Studies conducted with P2-derived peptides suggest
      that the conformation-specific antibody is directed to an acidic tripeptide, Asp
      Glu-Glu, and this sequence is also present in the cytoplasmic domain of the
      epidermal growth factor receptor. With respect to the C terminus amino acid or
      ATP-binding site, Asp-Glu-Glu is located in different regions in these receptors;
      nevertheless, this tripeptide along with the surrounding amino acids is cryptic
      in the unphosphorylated receptor, and tyrosine phosphorylation uncovers this
      site. This suggests that the Asp-Glu-Glu sequence may be important in receptor
      functions.

PMID- 7713897
TI  - Structure of the metal-free gamma-carboxyglutamic acid-rich membrane binding
      region of factor IX by two-dimensional NMR spectroscopy.
AB  - The gamma-carboxyglutamic acid-rich domain of blood coagulation Factor IX is
      required for the binding of the protein to phospholipid membranes. To investigate
      the three-dimensional structure of this domain, a synthetic peptide corresponding
      to residues 1-47 of Factor IX was studied by 1H NMR spectroscopy. In the absence
      of metal ions, the proton chemical shift dispersion in the one-dimensional NMR
      spectrum indicated that the peptide contains regular structural elements. Upon
      the addition of Ca(II) or Mg(II), large chemical shift changes were observed in
      the amide proton and methyl proton regions of the spectrum, consistent with the
      conformational transitions that metal ions are known to induce in native Factor
      IX. The apopeptide was studied by two-dimensional NMR spectroscopy at 500 MHz to
      determine its solution structure. Protons were assigned using total correlation
      spectroscopy, nuclear Overhauser effect spectroscopy, and double quantum-filtered
      correlation spectroscopy experiments. Intensities of cross-peaks in the nuclear
      Overhauser effect spectrum were used to generate a set of interproton distance
      restraints. The structure of the apopeptide was then calculated using distance
      geometry methods. There are three structural elements in the apopeptide that are
      linked by a flexible polypeptide backbone. These elements include a short amino
      terminal tetrapeptide loop (amino acids 6-9), the disulfide-containing
      hexapeptide loop (amino acids 18-23), and a carboxyl-terminal alpha helix (amino
      acids 37-46). Amide hydrogen exchange kinetics indicate that the majority of the
      peptide is solvent accessible, except in the carboxyl-terminal element. The
      structured regions in the apopeptide are insufficient to support phospholipid
      binding, indicating the importance of additional structural features in the
      Ca(II)-stabilized conformer.

PMID- 7713898
TI  - A conserved region in the amino terminus of DNA polymerase delta is involved in
      proliferating cell nuclear antigen binding.
AB  - Synthetic peptides to selected sequences in human DNA polymerase delta (pol
      delta) were used to identify the region involved in the interaction of pol delta
      to proliferating cell nuclear antigen. Peptides corresponding to sequences in
      five regions in the amino terminus of human pol delta and three in the carboxyl
      terminus, which are conserved with the yeast homologs of pol delta, were tested.
      These studies showed that the peptide corresponding to the N2 region (residues
      129-149) selectively and specifically inhibited the PCNA stimulation of pol
      delta. This inhibition was relieved by titration with excess PCNA. The
      identification of the N-2 region as being involved in PCNA binding was supported
      by studies that demonstrated that the N2 peptide could bind PCNA. Deletion
      mutants of pol delta expressed in Sf9 cells provided evidence that the binding
      region for PCNA was located in the first 182 residues of the amino terminus.
      These studies provide reasonable evidence that residues within the region 129-149
      of pol delta are involved in the binding site for PCNA.

PMID- 7713900
TI  - Calculation of absolute metabolic flux and the elucidation of the pathways of
      glutamate labeling in perfused rat heart by 13C NMR spectroscopy and nonlinear
      least squares analysis.
AB  - Absolute metabolic fluxes in isolated perfused hearts have been determined by a
      nonlinear least squares analysis of glutamate labeling kinetics from [1
      13C]glucose, [4-13C]beta-hydroxybutyrate, or [2-13C]acetate using 13C NMR
      spectroscopy. With glucose as substrate, the malate-aspartate shuttle flux was
      too slow to account for the reducing equivalents generated by glycolysis and to
      predict the observed oxygen consumption rate. For acetate and beta
      hydroxybutyrate, the malate-aspartate shuttle had to be reversed for the network
      to agree with the observed oxygen consumption and glutamate labeling. Thus, an
      additional redox shuttle was required to reoxidize the NADH produced by
      cytoplasmic malate dehydrogenase. Using this model there was good agreement
      between the experimentally determined oxygen consumption and glutamate labeling
      and the calculated values of these parameters from the model for all substrates.
      The contribution of exogenous substrate to the overall tricarboxylic acid (TCA)
      cycle flux, 89.6 +/- 6.5% (mean +/- S.D.) as measured in the tissue extracts
      compared well with 91.4 +/- 4.2% calculated by the model. The ratio of TCA cycle
      flux to oxygen consumption for acetate, was 2.2 +/- 0.1, indicating that NADH
      production is principally accounted for by TCA cycle flux. For glucose or beta
      hydroxybutyrate, this ratio was 2.9 +/- 0.2, consistent with the existence of
      other NADH producing reactions (e.g. glycolysis, beta-hydroxybutyrate oxidation).

PMID- 7713899
TI  - Expression of the catalytic subunit of human DNA polymerase delta in mammalian
      cells using a vaccinia virus vector system.
AB  - The catalytic polypeptide of human DNA polymerase delta was overexpressed in BSC
      40 cells (African green monkey kidney cell line) using the vaccinia virus/pTM1
      system. The recombinant human DNA polymerase delta was purified to homogeneity in
      two steps using an immunoaffinity column and a single-stranded DNA-cellulose
      column. Levels of expression were about 1% of soluble cytosolic protein. The
      recombinant catalytic subunit was fully active and exhibited enzymatic properties
      similar to that of the native two-subunit enzyme including the possession of an
      associated 3' to 5' exonuclease activity. Recombinant pol delta was stimulated by
      proliferating cell nuclear antigen (PCNA); however, the degree of stimulation was
      lower than that of the native human enzyme. Analysis of a double mutant of the
      catalytic subunit, H142R/F144S, showed that it had a greatly reduced sensitivity
      to PCNA, suggesting that the PCNA binding site of pol delta may be located in
      this region of the N terminus.

PMID- 7713902
TI  - Folding, flavinylation, and mitochondrial import of 6-hydroxy-D-nicotine oxidase
      fused to the presequence of rat dimethylglycine dehydrogenase.
AB  - We analyzed the folding, covalent flavinylation, and mitochondrial import of the
      rabbit reticulocyte lysate-translated bacterial 6-hydroxy-D-nicotine oxidase (6
      HDNO) fused to the mitochondrial targeting sequence of rat liver dimethylglycine
      dehydrogenase. Translation of 6-HDNO in FAD-supplemented reticulocyte lysate
      resulted in a protein that contained covalently incorporated FAD, exhibited
      enzyme activity, and was trypsin-resistant, a characteristic of the tight
      conformation of the holoenzyme. The attached mitochondrial presequence did not
      prevent folding, binding of FAD, or enzyme activity of the 6-HDNO moiety of the
      fusion protein (pre-6-HDNO). Pre-6-HDNO was imported into rat liver mitochondria
      and processed by the mitochondrial processing peptidase. Incubation of the
      trypsin-resistant pre-holo-6-HDNO protein with deenergized rat liver mitochondria
      demonstrated that upon contact with mitochondria, the protein was unfolded and
      became trypsin sensitive. Mitochondrial import assays showed that the unfolded
      pre-holo-6-HDNO with covalently attached FAD was imported into rat liver
      mitochondria. Inside the mitochondrion the holo-6-HDNO was refolded into the
      trypsin-resistant conformation. However, when pre-apo-6-HDNO was imported only
      part of the protein became trypsin resistant (approximately 20%). Addition of FAD
      and the allosteric effector glycerol 3-phosphate to apo-6-HDNO containing
      mitochondrial matrix was required to transform the protein into the trypsin
      resistant conformation characteristic of holo-6-HDNO.

PMID- 7713901
TI  - Nonreducing end structures of chondroitin sulfate chains on aggrecan isolated
      from Swarm rat chondrosarcoma cultures.
AB  - Chondrocyte cultures derived from the Swarm rat chondrosarcoma were metabolically
      labeled with [35S]sulfate or [6-3H]GlcN. Radiolabeled aggrecan was purified from
      the cell layer and exhaustively digested with chondroitin ABC lyase. Digestion
      products were resolved into disaccharide and monosaccharide residues using
      Toyopearl HW40S chromatography. The separated saccharide pools were reduced with
      NaBH4 and applied onto a CarboPac PA1 column to resolve all of the internal
      disaccharide alditols (unsaturated) from the nonreducing end disaccharide
      (saturated) and monosaccharide alditols. Mercuric acetate treatment was used
      prior to carbohydrate analysis to identify unambiguously the saturated from the
      unsaturated disaccharides. The chondroitin sulfate (CS) chains from these
      aggrecan preparations contained: (a) an internal disaccharide composition of
      unsulfated (3-4 per chain), 4-sulfated (approximately 32 per chain), 6-sulfated
      (approximately 1 per 14 chains), and 4,6-sulfated disaccharides (approximately 1
      per 6 chains) and (b) a nonreducing terminal composition of 4-sulfated GalNAc
      (approximately 4 out of every 7 chains), 4,6-disulfated GalNAc (approximately 2
      out of every 7 chains), and GlcUA adjacent to a 4-sulfated GalNAc residue
      (approximately 1 out of every 7 chains). Thus, the vast majority of these CS
      chains terminated with a sulfated GalNAc residue. The presence of 4,6-disulfated
      GalNAc at nonreducing termini is 60-fold more abundant than 4,6-disulfated GalNAc
      in interior disaccharides. This observation is consistent with the suggestion
      that disulfation of terminal GalNAc residues is involved in chain termination.

PMID- 7713904
TI  - Calmodulin, a junction between two independent immunosuppressive pathways in
      Jurkat T cells.
AB  - Calmodulin (CaM) antagonists chlorpromazine, trifluoperazine, and N-(6
      aminohexyl)-5-chloro-1-naphthalene-sulfonamide HCl inhibit Jurkat T cell
      activation, as monitored by measuring interleukin-2 synthesis in cells treated by
      a combination of CD3 monoclonal antibody and phorbol myristate acetate. T cell
      activation with CD3 monoclonal antibody is accompanied by a decreased synthesis
      of phosphatidylserine due to the release of Ca2+ from the endoplasmic reticulum.
      CaM antagonists reverse the phosphatidylserine (PtdSer) inhibition induced by
      CD3. This increase of PtdSer synthesis was observed in the absence of any
      modification of CD3-induced Ca2+ movements. Both in intact cells and in an
      acellular system, the increase of PtdSer synthesis induced by CaM antagonists was
      abolished in the presence of EGTA, indicating that the base exchange enzyme
      system responsible for PtdSer synthesis is regulated by CaM provided that Ca2+ is
      present. By contrast, cyclosporin A that inhibits T cell activation through the
      interaction of cyclophilin-cyclosporin A complexes with the calmodulin-activated
      phosphatase, calcineurin, had no effect on PtdSer synthesis. Calmodulin thus
      appears as a junction leading to at least two independent pathways of regulation
      of T cell activation, one involving the calcineurin phosphatase and the other the
      base exchange enzyme system responsible for PtdSer synthesis.

PMID- 7713903
TI  - Brefeldin A renders Chinese hamster ovary cells insensitive to transcriptional
      suppression by 25-hydroxycholesterol.
AB  - The effect of disruption of the Golgi apparatus on 25-hydroxycholesterol-mediated
      transcriptional suppression and activation of acyl-CoA:cholesterol
      acyltransferase was examined. In Chinese hamster ovary (CHO) cells, brefeldin A
      (BFA) caused dose-dependent inhibition of 25-hydroxycholesterol-mediated
      suppression of mRNAs for four sterol-regulated genes: 3-hydroxy-3-methylglutaryl
      (HMG)-CoA reductase, HMG-CoA synthase, farnesyl-diphosphate synthase, and the low
      density lipoprotein receptor. BFA prevented suppression whether added prior to or
      following a 4-h pretreatment with 25-hydroxycholesterol. In the presence of BFA
      (1 microgram/ml), 25-hydroxycholesterol-mediated suppression of mRNAs for HMG-CoA
      reductase, the low density lipoprotein receptor, and farnesyl-diphosphate
      synthase was almost completely blocked. HMG-CoA synthase mRNA was 80-90%
      suppressed by 25-hydroxycholesterol compared with 50-60% suppression in the
      presence of BFA. These effects of BFA were not due to alterations in mRNA
      stability. Disruption of the Golgi apparatus, as assessed by staining with a
      fluorescent lectin, correlated with concentrations of BFA that reversed mRNA
      suppression. Monensin was also found to block the effects of 25
      hydroxycholesterol on suppression of HMG-CoA reductase. However, this ionophore
      decreased the other three sterol-regulated mRNAs to a similar degree as 25
      hydroxycholesterol. In contrast to CHO cells, BFA-resistant PtK1 cells displayed
      normal down-regulation of HMG-CoA reductase and an intact Golgi apparatus in the
      presence of BFA and 25-hydroxycholesterol. Cholesterol esterification in CHO
      cells was stimulated to a similar extent by BFA (1 microgram/ml) and 25
      hydroxycholesterol, and simultaneous treatment of CHO cells with both compounds
      was 60-70% additive. These results suggest that an intact Golgi apparatus is
      required for 25-hydroxycholesterol-mediated suppression of mRNA.

PMID- 7713905
TI  - Expression of antisense to DNA methyltransferase mRNA induces DNA demethylation
      and inhibits tumorigenesis.
AB  - Many tumor cell lines overexpress DNA methyltransferase (MeTase) activity;
      however it is still unclear whether this increase in DNA MeTase activity plays a
      causal role in naturally occurring tumors and cell lines, whether it is critical
      for the maintenance of transformed phenotypes, and whether inhibition of the DNA
      MeTase in tumor cells can reverse transformation. To address these basic
      questions, we transfected a murine adrenocortical tumor cell line Y1 with a
      chimeric construct expressing 600 base pairs from the 5' of the DNA MeTase cDNA
      in the antisense orientation. The antisense transfectants show DNA demethylation,
      distinct morphological alterations, are inhibited in their ability to grow in an
      anchorage-independent manner, and exhibit decreased tumorigenicity in syngeneic
      mice. Ex vivo, cells expressing the antisense construct show increased serum
      requirements, decreased rate of growth, and induction of an apoptotic death
      program upon serum deprivation. 5-Azadeoxycytidine-treated cells exhibit a
      similar dose-dependent reversal of the transformed phenotype. These results
      support the hypothesis that the DNA MeTase is actively involved in oncogenic
      transformation.

PMID- 7713906
TI  - The Ca(2+)-mobilizing actions of a Jurkat cell extract on mammalian cells and
      Xenopus laevis oocytes.
AB  - Randriamampita and Tsien (Randriamampita, C., and Tsien, R. Y. (1993) Nature 364,
      809-814) suggested that an acid-extracted fraction from a Jurkat cell line
      contains a messenger responsible for the coupling of calcium entry to the
      depletion of intracellular stores, i.e. capacitative calcium entry. We found that
      the extract, prepared as described by Randriamampita and Tsien, caused Ca2+ entry
      in 1321N1 astrocytoma cells which was not blocked by the D-myo-1,4,5
      trisphosphate-receptor antagonist, heparin. In contrast to astrocytoma cells,
      when applied to mouse lacrimal acinar cells and rat hepatocytes the Jurkat
      extract always caused the release of intracellular Ca2+, followed by Ca2+ entry
      across the plasma membrane. This activity of the extract on lacrimal cells was
      blocked by either intracellular injection of heparin or extracellular atropine.
      Similarly prepared lacrimal cell extracts gave Ca2+ responses when applied to
      astrocytoma cells or lacrimal cells which were similar to those for Jurkat
      derived extract. However, extracts from hepatocytes had no effect. In most
      Xenopus oocytes, the Jurkat extract had no effect, while in a few oocytes, the
      extract gave a [Ca2+]i response similar to that seen in lacrimal cells, that is,
      release of Ca2+ followed by Ca2+ entry. We conclude that the actions of the
      Jurkat cell extract are not consistent with its containing the long sought
      messenger for capacitative calcium entry. It is likely that this fraction
      contains a number of factors that mediate Ca2+ response in different cell types,
      possibly through receptor-mediated mechanisms.

PMID- 7713907
TI  - Irreversible inactivation of protein kinase C by a peptide-substrate analog.
AB  - Protein kinase C (PKC) is a phospholipid-dependent isozyme family that plays a
      pivotal role in mammalian signal-transduction pathways that mediate cell growth
      and differentiation and pathological developments, such as the acquisition of
      drug resistance by cancer cells. Several peptide-substrate analogs have been
      shown to reversibly inhibit PKC with high potency and selectivity, but peptide
      substrate analogs that antagonize PKC by forming a covalent complex with the
      enzyme have not been reported. The development of active site-directed
      irreversible inactivators of PKC could provide new insights into the catalytic
      mechanism and might ultimately lead to the design of novel therapeutics targeted
      at PKC. In this report, we show that the peptide-substrate analog Arg-Lys-Arg-Cys
      Leu-Arg-Arg-Leu (RKRCLRRL) irreversibly inactivates PKC in a dithiothreitol
      sensitive manner. The inactivation mechanism most consistent with our results is
      the formation of a covalent linkage between the inhibitor-peptide and the enzyme
      at its active-site. Limited proteolysis of PKC produces a catalytic-domain
      fragment that is independent of the phospholipid cofactor. RKRCLRRL antagonized
      the histone kinase activity of PKC and its catalytic-domain fragment with similar
      efficacies, achieving > 50% inactivation at an RKRCLRRL concentration of 10
      microM. In contrast, RKRCLRRL analogs with single amino acid substitutions at Cys
      were non-inhibitory. The inactivated complex of the catalytic-domain fragment and
      RKRCLRRL was stable upon dilution, and the inactivation of PKC and the catalytic
      domain fragment by RKRCLRRL was quenched by dithiothreitol, providing evidence
      that the enzyme and the synthetic peptide may be covalently linked in an
      inactivated complex by a disulfide bond. Substrates and substrate analogs
      protected the catalytic-domain fragment against inactivation by RKRCLRRL,
      providing evidence that inactivation entailed binding of RKRCLRRL at the active
      site of the enzyme. S-Thiolation is the formation of mixed disulfides between
      proteins and low molecular weight thiols. PKC is thought to have a highly
      reactive Cys residue in its active-site, and Cys residues that are flanked by
      basic residues, as is the case in RKRCLRRL, display enhanced reactivity. Our
      results support an inactivation mechanism that entails S-thiolation of the active
      site of PKC by RKRCLRRL. This is the first report of irreversible inactivation of
      PKC by an active site-directed peptide.

PMID- 7713908
TI  - C/EBP-related sites in addition to a STAT site are necessary for ciliary
      neurotrophic factor-leukemia inhibitory factor-dependent transcriptional
      activation by the vasoactive intestinal peptide cytokine response element.
AB  - The neuropoietic cytokines ciliary neurotrophic factor (CNTF) and leukemia
      inhibitory factor (LIF) regulate VIP gene expression through a cytokine response
      element (CyRE) which interacts with members of the STAT transcription factor
      family. The CyRE STAT site is, however, insufficient to mediate full
      transcriptional activation by CNTF/LIF, suggesting that other sequences and
      nuclear proteins are also important. As C/EBP proteins participate in the
      transcriptional effects of the related cytokine, interleukin-6, we investigated
      the role of possible C/EBP-binding sites in the response of the VIP CyRE to
      CNTF/LIF. Using DNase I footprinting, transactivation studies, DNA mobility shift
      assays, and mutational analysis, three sites within the VIP CyRE were identified
      as C/EBP-related binding sites and shown to be important to CNTF/LIF-mediated
      transcriptional activation. The CyRE C/EBP-related sites interact with nuclear
      proteins from the human neuroblastoma cell line, NBFL, including a novel, protein
      synthesis-dependent, nuclear protein complex, induced by CNTF treatment. These
      nuclear proteins are not, however, recognized by antisera to known C/EBP
      proteins. Therefore, other nuclear proteins regulated by independent pathways act
      in concert with the JAK-STAT pathway to mediate CNTF/LIF regulation of VIP gene
      expression through the CyRE.

PMID- 7713909
TI  - Cloning of a human cDNA for protoporphyrinogen oxidase by complementation in vivo
      of a hemG mutant of Escherichia coli.
AB  - Protoporphyrinogen oxidase (PPO; EC 1.3.3.4) is the enzyme that catalyzes in the
      penultimate step in the heme biosynthetic pathway. Hemes are essential components
      of redox enzymes, such as cytochromes. Thus, a hemG mutant strain of Escherichia
      coli deficient in PPO is defective in aerobic respiration and grows poorly even
      in rich medium. By complementation with a human placental cDNA library, we were
      able to isolate a clone that enhanced the poor growth of such a hemG mutant
      strain. The clone encoded the gene for human PPO. Sequence analysis revealed that
      PPO consists of 477 amino acids with a calculated molecular mass of 50.8
      kilodaltons. The deduced protein exhibited a high degree of homology over its
      entire length to the amino acid sequence of PPO encoded by the hemY gene of
      Bacillus subtilis. The NH2-terminal amino acid sequence of the deduced PPO
      contains a conserved amino acid sequence that forms the dinucleotide-binding site
      in many flavin-containing proteins. Northern blot analysis revealed the synthesis
      of a 1.8-kilobase pair mRNA for PPO. A homogenate of the monkey kidney COS-1
      cells that had been transfected with the cDNA had much higher PPO activity than
      an extract of control cells, and this activity was inhibited by acifluorfen, a
      specific inhibitor of PPO. Furthermore, the cDNA was expressed in vitro as 51
      kilodalton protein, and after incubation with isolated mitochondria the protein
      was found to be located in the mitochondria, having just the same size as before,
      an indication that PPO is a mitochondrial enzyme and has no apparent transport
      specific leader sequence.

PMID- 7713910
TI  - Lipoprotein lipase association with lipoproteins involves protein-protein
      interaction with apolipoprotein B.
AB  - Lipoprotein lipase (LPL) hydrolyzes chylomicron and very low density lipoprotein
      (VLDL) triglycerides and potentiates the cellular uptake of lipoproteins. These
      LPL-lipoprotein associations could involve only protein-lipid interaction, or
      they could be modulated by apolipoproteins (apo). ApoB is the major protein
      component of chylomicrons, VLDL, and low density lipoprotein (LDL). ApoB100, a
      large glycoprotein with a molecular mass of 550 kDa, is composed of several
      functional domains. A carboxyl-terminal region of the protein is the ligand for
      the LDL receptor. There are several hydrophobic domains that are believed to be
      important in lipid binding. The relatively hydrophilic amino-terminal region of
      apoB, however, has no known function. Using solid phase assays we quantified LPL
      lipoprotein complex formation. On a molar basis, severalfold greater amounts of
      LPL bound to LDL and VLDL than to high density lipoprotein at all the
      concentrations of LPL tested (0.9-55 nM). To assess the roles of LDL protein
      versus lipid, we performed competition and ligand blotting experiments. LDL and
      an amino-terminal fragment of apoB competed better for 125I-LPL binding to LDL
      than did lipid emulsion particles. Delipidation of LDL-coated plates did not
      alter LPL binding. On ligand blots, LPL bound to amino-terminal fragments of apoB
      generated by thrombin digestion but not to apoA1, apoE, or carboxyl-terminal
      fragments of apoB. Further evidence for LPL interaction with the amino-terminal
      region of apoB was obtained using anti-apoB monoclonal antibodies. Antibodies
      directed against the amino-terminal regions of apoB blocked LPL interaction with
      LDL, whereas those against the carboxyl-terminal region of apoB did not inhibit
      LPL interaction with LDL. Thus, we conclude that a specific interaction between
      LPL and the amino-terminal region of apoB may facilitate LPL association with
      circulating lipoproteins.

PMID- 7713911
TI  - Distinctive roles of the two ATP-binding sites in ClpA, the ATPase component of
      protease Ti in Escherichia coli.
AB  - ClpA is the ATPase component of the ATP-dependent protease Ti (Clp) in
      Escherichia coli and contains two ATP-binding sites. A ClpA variant (referred to
      as ClpAT) carrying threonine in place of the 169th methionine has recently been
      shown to be highly soluble but indistinguishable from the wild-type, 84-kDa ClpA
      in its ability to hydrolyze ATP and to support the casein-degrading activity of
      ClpP. Therefore, site-directed mutagenesis was performed to generate mutations in
      either of the two ATP-binding sites of ClpAT (i.e. to replace the Lys220 or
      Lys501 with Thr). ClpAT/K220T hydrolyzed ATP and supported the ClpP-mediated
      proteolysis 10-50% as well as ClpAT depending on ATP concentration, while
      ClpAT/K501T was unable to cleave ATP or to support the proteolysis. Without ATP,
      ClpAT and both of its mutant forms behaved as trimeric molecules as analyzed by
      gel filtration on a Sephacryl S-300 column. With 0.5 mM ATP, ClpAT and
      ClpAT/K501T became hexamers, but ClpAT/K220T remained trimeric. With 2 mM ATP,
      however, ClpAT/K220T also behaved as a hexamer. These results suggest that the
      first ATP-binding site of ClpA is responsible for hexamer formation, while the
      second is essential for ATP hydrolysis. When trimeric ClpAT/K220T was incubated
      with the same amount of hexameric ClpAT/K501T (i.e. at 0.5 mM ATP) and then
      subjected to gel filtration as above, a majority of ClpAT/K220T ran together with
      ClpAT/K501T as hexameric molecules. Furthermore, ClpAT/K501T in the mixture
      strongly inhibited the ability of ClpAT/K220T to cleave ATP and to support the
      ClpP-mediated proteolysis. Similar results were obtained in the presence of 2 mM
      ATP and also with the mixture with ClpAT. On the other hand, the ATPase activity
      of the mixture of ClpAT and ClpAT/K220T was significantly higher than the sum of
      that of each protein, particularly in the presence of 2 mM ATP, although its
      ability to support the proteolysis by ClpP remained unchanged. These results
      suggest that a rapid exchange of the subunits, possibly as a trimeric unit,
      occurs between the ClpAT proteins in the presence of ATP and leads to the
      formation of mixed hexameric molecules.

PMID- 7713913
TI  - Coordination of Ca2+ signaling by intercellular propagation of Ca2+ waves in the
      intact liver.
AB  - Activation of the inositol lipid signaling system results in cytosolic Ca2+
      oscillations and intra- and intercellular Ca2+ waves in many isolated cell
      preparations. However, this form of temporal and spatial organization of
      signaling has not been demonstrated in intact tissues. Digital imaging
      fluorescence microscopy was used to monitor Ca2+ at the cellular and subcellular
      level in intact perfused rat liver loaded with fluorescent Ca2+ indicators.
      Perfusion with low doses of vasopressin induced oscillations of hepatocyte Ca2+
      that were coordinated across entire lobules of the liver by propagation of Ca2+
      waves along the hepatic plates. At the subcellular level these periodic Ca2+
      waves initiated from the sinusoidal domain of cells within the periportal region
      and propagated radially across cell-cell contacts into the pericentral region, or
      until terminated by annihilation collision with other Ca2+ wave fronts. With
      increasing agonist dose, the frequency but not the amplitude of the Ca2+ waves
      increased. Intracellular Ca2+ wave rates were constant, but transcellular signal
      propagation was determined by agonist dose, giving rise to a dose-dependent
      increase in the rate at which Ca2+ waves spread through the liver. At high
      vasopressin doses, a single Ca2+ wave was observed and the direction of Ca2+ wave
      propagation was reversed, initiating in the pericentral region and spreading to
      the periportal region. It is concluded that intercellular Ca2+ waves may provide
      a mechanism to coordinate responses across the functional units of the liver.

PMID- 7713912
TI  - A tetrad of ionizable amino acids is important for catalysis in barley beta
      glucanases.
AB  - Determination of the crystal structures of a 1,3-beta-D-glucanase (E.C. 3.2.1.39)
      and a 1,3-1,4-beta-D-glucanase (E.C. 3.2.1.73) from barley (Hordeum vulgare)
      (Varghese, J.N, Garrett, T. P. J., Colman, P. M., Chen, L., Hoj, P. B., and
      Fincher, G. B. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 2785-2789) showed the
      spatial positions of the catalytic residues in the substrate-binding clefts of
      the enzymes and also identified highly conserved neighboring amino acid residues.
      Site-directed mutagenesis of the 1,3-beta-glucanase has now been used to
      investigate the importance of these residues. Substitution of glutamine for the
      catalytic nucleophile Glu231 (mutant E231Q) reduced the specific activity about
      20,000-fold. In contrast, substitution of glutamine for the catalytic acid Glu288
      (mutant E288Q) had less severe consequences, reducing kcat approximately 350-fold
      with little effect on Km. Substitution of two neighboring and strictly conserved
      active site-located residues Glu279 (mutant E279Q) and Lys282 (mutant K282M) led
      to 240- and 2500-fold reductions of Kcat, respectively, with small increases in
      Km. Thus, a tetrad of ionizable amino acids is required for efficient catalysis
      in barley beta-glucanases. The active site-directed inhibitor 2,3-epoxypropyl
      beta-laminaribioside was soaked into native crystals. Crystallographic refinement
      revealed all four residues (Glu231, Glu279, Lys282, and Glu288) to be in contact
      with the bound inhibitor, and the orientation of bound substrate in the active
      site of the glucanase was deduced.

PMID- 7713914
TI  - Gene structure and expression of human thyroid transcription factor-1 in
      respiratory epithelial cells.
AB  - The human gene encoding thyroid transcription factor-1 (TTF-1), a homeodomain
      containing nuclear transcription protein of the Nkx2 gene family, was isolated
      and characterized. Human TTF-1 was encoded by a single gene locus spanning
      approximately 3.3 kilobases and consisted of two exons and a single intron. The
      TTF-1 cDNA and polypeptide of 371 amino acids have been highly conserved, sharing
      98% identity with the rat TTF-1 polypeptide. Human TTF-1 mRNA and polypeptide
      were selectively expressed in human and mouse pulmonary adenocarcinoma cell
      lines. In addition to its presence in thyroid gland epithelium, the human TTF-1
      protein was detected by immunohistochemistry in human fetal lung as early as 11
      weeks of gestation, being localized in the nuclei of epithelial cells of the
      developing airways. After birth, TTF-1 was selectively expressed in Type II
      epithelial cells in the alveoli and in subsets of bronchiolar epithelial cells in
      the conducting regions of the lung. The 5'-flanking region of the human TTF-1
      gene directed transcription of luciferase cDNA in a lung epithelial cell
      selective manner. The conservation and distribution of TTF-1 in the human
      respiratory tract support its role in the regulation of lung development and
      surfactant homeostasis.

PMID- 7713915
TI  - Identification of gangliosides as inhibitors of ADP-ribosyltransferases of
      pertussis toxin and exoenzyme C3 from Clostridium botulinum.
AB  - We have previously reported the presence of an endogenous inhibitory activity in
      bovine brain for the ADP-ribosylation of GTP-binding proteins catalyzed by
      pertussis toxin (PT) (Hara-Yokoyama, M., and Furuyama, S. (1989) Biochem.
      Biophys. Res. Commun. 160, 67-71). In the present study, we identified the
      inhibitor as a ganglioside. The screening of various gangliosides revealed that
      GQ1b alpha most effectively inhibited the ADP-ribosyltransferase activities of
      both the holoenzyme and the catalytic subunit of PT. GQ1b alpha is a ganglioside
      newly identified as one of the antigens recognized by the cholinergic neuron
      specific antibody, anti-Chol-1 alpha (Hirabayashi, Y., Nakao, T., Irie, F.,
      Whittaker, V.P., Kon, K., and Ando, S. (1992) J. Biol. Chem. 267, 12973-12978).
      GQ1b alpha also inhibited the PT-catalyzed NAD+ glycohydrolysis. Unlike PT
      activity, the ADP-ribosylation and the NAD+ glycohydrolysis catalyzed by the C3
      exoenzyme from Clostridium botulinum type C were inhibited by GT1b and GQ1b. The
      ADP-ribosylation catalyzed by either PT or the C3 exoenzyme was not inhibited by
      ceramide, galactocerebroside, or sialic acid. In addition to the inhibitory
      action of gangliosides on ADP-ribosylation, the importance of gangliosides as
      regulators of NAD+ metabolism is discussed.

PMID- 7713916
TI  - Expression, characterization, and crystallization of the catalytic core of the
      human insulin receptor protein-tyrosine kinase domain.
AB  - The deduced primary sequence of the cytoplasmic protein-tyrosine kinase domain of
      the insulin receptor contains a conserved kinase homology region (receptor
      residues 1002-1257) flanked by a juxtamembrane region and a C-terminal tail. A
      soluble 48-kDa derivative (residues 959-1355) containing these regions but
      lacking the first six residues of the juxtamembrane region had earlier been
      synthesized in Sf9 cells using a baculovirus expression system. The catalytic
      core of the kinase domain was studied first by proteolytic analysis of the 48-kDa
      kinase and then by expressing a series of truncated kinase domains in transiently
      transfected COS cells. Based on these studies, two core kinases of 34 (residues
      985-1283) and 35 (residues 978-1283) kDa, respectively, were overexpressed in Sf9
      cells. Biochemical characterization of the 35-kDa kinase revealed that the core
      kinase conserved the major functional properties of the native receptor kinase
      domain. Activity of the 35-kDa kinase toward a synthetic peptide increased more
      than 200-fold upon autophosphorylation, which occurred exclusively at Tyr-1158,
      Tyr-1162, and Tyr-1163; the largest increase was observed between bis- and
      trisphosphorylation of the kinase. The activated 35- and 48-kDa kinases were
      similar with respect to specific activity and ATP and Mg2+ requirements for
      peptide phosphorylation. Moreover, autophosphorylation appeared to initiate
      predominantly at Tyr-1162, immediately followed by phosphorylation at Tyr-1158
      and then at Tyr-1163. The rate of autophosphorylation was dependent on enzyme
      concentration, consistent with a trans-phosphorylation mechanism. Finally, the 35
      kDa kinase was crystallized, making possible elucidation of its three-dimensional
      structure by x-ray crystallography.

PMID- 7713917
TI  - Structure, genomic organization, and expression of the Arabidopsis thaliana
      aconitase gene. Plant aconitase show significant homology with mammalian iron
      responsive element-binding protein.
AB  - We report the purification of the unstable aconitase enzyme from melon seeds and
      the NH2-terminal amino acid sequence determination. Antibodies raised against
      this protein enabled the first isolation and characterization of cDNA encoding
      aconitase in plants. A full-length cDNA clone of 3210 base pairs was isolated
      from a library of cDNA clones derived from immature pods of Arabidopsis thaliana.
      The amino acid sequence deduced from the open reading frame includes the sequence
      obtained by direct sequencing of the NH2 terminus of the purified enzyme. Genomic
      clones of the aconitase gene were isolated, and comparison of the cDNA and
      genomic sequences reveals that the coding sequence is divided among 20 exons.
      There are five putative sites for transcription initiation. The aconitase gene is
      constitutively expressed, but at a low level, during most developmental stages,
      with a dramatic increase during seed and pollen maturation and during
      germination. Surprisingly, plant aconitases have reasonably high homology to
      binding proteins for iron-responsive elements from mammalian species, opening the
      possibility that a similar type of translational regulation occurs in plants.

PMID- 7713918
TI  - Structure-function analysis of human alpha 1-->3fucosyltransferases. A GDP-fucose
      protected, N-ethylmaleimide-sensitive site in FucT-III and FucT-V corresponds to
      Ser178 in FucT-IV.
AB  - Human alpha 1-->3fucosyltransferases constitute a family of closely related
      membrane-bound enzymes distinguished by differences in acceptor specificities and
      inherent protein biochemical properties. One such biochemical property is
      sensitivity to enzyme inactivation by sulfhydral-group modifying reagents such as
      N-ethylmaleimide. The basis for this property has been studied using a fusion
      protein of FucT-III and FucT-V composed of Protein A coupled to the catalytic
      domain of the enzyme. The results indicate that modification of FucT-V by 5,5'
      dithiobis(2-nitrobenzoic acid) resulted in efficient enzyme inactivation that
      could be reversed by excess thiol reagent suggesting that the free sulfhydral
      group on the enzyme was required for activity. Recombinant forms of both FucT-III
      and FucT-V were irreversibly inactivated by N-ethylmaleimide and could be
      effectively protected from inactivation by GDP-fucose and GDP but not by UDP
      galactose, fucose, or N-acetyllactosamine. Analysis of the distribution of Cys
      residues in aligned sequences of cloned human alpha 1-->3fucosyltransferases
      indicated one site, Cys143 of FucT-III and Cys156 of FucT-V, corresponded to the
      highly conservative replacement of Ser178 in FucT-IV, an enzyme insensitive to N
      ethylmaleimide. A site-directed mutagenesis experiment was performed to replace
      Ser178 of FucT-IV with a Cys residue. The mutant FucT-IV enzyme was active;
      however, the Km for GDP-fucose was increased about 3-fold compared to the native
      enzyme to 28 +/- 3 microM. This enzyme was N-ethylmaleimide sensitive and could
      be partially protected by GDP-fucose but not N-acetyllactosamine. These results
      support the importance of Ser178 of FucT-IV in donor substrate binding and
      strongly suggest analogous Cys residues are the GDP-fucose protectable, N
      ethylmaleimide-sensitive sites present in FucT-III and -V.

PMID- 7713919
TI  - Membrane expression and interactions of human transcobalamin II receptor.
AB  - Antiserum raised to purified 62-kDa human placental transcobalamin II receptor
      (TC II-R) has been used to study its synthesis and membrane expression. The
      antiserum immunoprecipitated a 45-kDa protein from the cell-free translation
      using human kidney mRNA and recognized a single 124-kDa band on immunoblotting of
      placental and other human tissue membranes, and quantitation of the blots
      revealed high levels of TC II-R expression in the human kidney followed by
      placenta, intestine, and liver. Triton X-100 extraction of placental membranes
      resulted in the complete (100%) solubilization of the receptor, and
      immunoblotting of the Triton X-100-soluble fraction revealed a single band of 62
      kDa. Lipid extraction of placental membranes with a mixture of chloroformmethanol
      (2:1) followed by immunoblotting revealed a single band of molecular mass 62 kDa.
      The molecular mass of the pure Triton X-100-bound receptor increased on SDS
      polyacrylamide gel electrophoresis from 62 to 124 kDa upon its insertion in
      liposomes prepared using egg phosphatidylcholine and cholesterol. Chemical cross
      linking of native membrane-or lipid vesicle-bound TC II-R or detergent-soluble
      extracts of the membrane with 125I-TC II-cobalamin revealed that both the 124-
      and 62-kDa forms of the receptor were active in ligand binding. Based on these
      results we suggest that TC II-R is synthesized as a single polypeptide of 45 kDa,
      and following its maturation (involving N- and O-glycosylation) the 62-kDa mature
      receptor is expressed in plasma membranes as a noncovalent dimer of 124 kDa. The
      dimerization of TC II-R in the plasma membranes is due to its interactions with
      annular lipids.

PMID- 7713920
TI  - Combining two mutations of human interleukin-6 that affect gp130 activation
      results in a potent interleukin-6 receptor antagonist on human myeloma cells.
AB  - The pleiotropic cytokine interleukin-6 (IL-6) interacts with the specific ligand
      binding subunit (IL-6R alpha) of the IL-6 receptor, and this complex associates
      with the signal-transducing subunit gp130 (IL-6R beta). Human IL-6 acts on human
      and murine cells, whereas murine IL-6 is only active on murine cells. The
      construction of a set of chimeric human/murine IL-6 proteins has recently allowed
      us to define a region (residues 43-55) within the human IL-6 protein, which is
      important for the interaction with gp130. Subdividing this region shows that
      mainly residues 50-55 of the human IL-6 are necessary for this interaction.
      Recently, another human IL-6 double mutant (Q159E and T162P) showed reduced
      affinity to gp130 but residual activity on the human myeloma cell line XG-1. Into
      this IL-6 mutant we introduced the murine residues 43-49 or 50-55 together with
      two point mutations, F170L and S176A, which had been reported to increase the
      affinity of IL-6 to the IL-6R alpha. The resulting IL-6 molecule, which contained
      the murine residues 50-55, was inactive on human myeloma cells and in addition
      completely inhibited wild type IL-6 activity on these cells. Such an antagonist
      may be used as a specific inhibitor of IL-6 activity in vivo.

PMID- 7713921
TI  - A novel role for IgG-Fc. Transductional potentiation for human high affinity Fc
      gamma receptor (Fc gamma RI) signaling.
AB  - Human type 1 Fc gamma receptors (Fc gamma RI) bind with high affinity (Kd =
      approximately 10(-9) M) Fc regions of monomeric IgG1 and IgG3. As demonstrated in
      this report, interaction of IgG-Fc with the ligand binding site on Fc gamma RI
      alters its capacity for aggregation-dependent signaling. This Fc-dependence was
      demonstrated in normal monocytes and U937-10.6 cells exposed to monomeric IgG and
      then to anti-Fc gamma RI F(ab')2 that cross-link the receptor. Using O2-
      production to measure cell signaling, we found that binding by high affinity IgGs
      of various species, as well as by murine hybrid IgGs containing only one high
      affinity heavy chain, resulted in a marked increase in Fc gamma RI-mediated
      signaling. Preaggregated Fc gamma RI/IgG had a ratio of one. IgG binding after
      aggregation of unligated Fc gamma RI did not restore signaling. Dose responses
      indicated that concentrations of IgG that saturated Fc gamma RI optimized
      transductional activity. The inclusion of unligated with ligated Fc gamma RI in
      aggregates depressed activity, indicating a lack of trans-activation of unligated
      Fc gamma RI. Significantly, IgG-binding markedly increased aggregation-dependent
      tyrosine phosphorylation of Fc gamma RI gamma-chains and the association of
      tyrosine phosphorylated Syk. Thus, the consequences of IgG-Fc binding were
      increases in aggregation-dependent phosphorylation of Fc gamma RI gamma-chains,
      recruitment of pp72Syk to Fc gamma RI, and signaling of the NADPH oxidase
      pathway.

PMID- 7713922
TI  - Methotrexate inhibits proteolysis of dihydrofolate reductase by the N-end rule
      pathway.
AB  - The N-end rule relates the in vivo half-life of a protein to the identity of its
      N-terminal residue. In eukaryotes, the N-end rule pathway is a ubiquitin
      dependent, proteasome-based system that targets and processively degrades
      proteins bearing certain N-terminal residues. Arg-DHFR, a modified dihydrofolate
      reductase bearing an N-terminal arginine (destabilizing residue in the N-end
      rule), is short lived in ATP-supplemented reticulocyte extract. It is shown here
      that methotrexate, which is a folic acid analog and high affinity ligand of DHFR,
      inhibits the degradation but not ubiquitination of Arg-DHFR by the N-end rule
      pathway. The degradation of other N-end rule substrates is not affected by
      methotrexate. We discuss implications of these results for the mechanism of
      proteasome-mediated protein degradation.

PMID- 7713923
TI  - Calreticulin, an antithrombotic agent which binds to vitamin K-dependent
      coagulation factors, stimulates endothelial nitric oxide production, and limits
      thrombosis in canine coronary arteries.
AB  - Coagulation Factor IX/IXa has been shown to bind to cellular surfaces, and Factor
      IXa expresses its procoagulant activity by assembling into the intrinsic Factor X
      activating complex (Factors IXa/VIIIa/X), which also forms on membrane surfaces.
      This led us to identify cellular proteins which bind Factor IX/IXa; an
      approximately 55-kDa polypeptide was purified to homogeneity from bovine lung
      extracts based on its capacity to bind 125I-Factor IX in a dose-dependent and
      saturable manner. From protein sequence data of the amino terminus and internal
      peptides, the approximately 55-kDa polypeptide was identified as calreticulin, a
      previously identified intracellular calcium-binding protein. Recombinant
      calreticulin bound vitamin K-dependent coagulation factors, 125I-Factor IX, 125I
      Factor X, and 125I-prothrombin (Kd values of approximately 2.7, 3.2, and 8.3 nM,
      respectively), via interaction with its C-domain, although it did not affect the
      coagulant properties of these proteins. 125I-Calreticulin also bound to
      endothelial cells in vitro (Kd approximately 7.4 nM), and mouse infusion studies
      showed an initial rapid phase of clearance in which calreticulin could be
      localized on the vascular endothelium. Exposure of endothelial cells to
      calreticulin led to dose-dependent, immediate, and sustained increase in the
      production of nitric oxide, as measured using a porphyrinic microsensor. In a
      canine electrically induced thrombosis model, intracoronary infusion of
      calreticulin (n = 7) prevented occlusion of the left circumflex coronary artery
      in a dose-dependent manner compared with vehicle-treated controls (n = 5). These
      results indicate that calreticulin interacts with the endothelium to stimulate
      release of nitric oxide and inhibit clot formation.

PMID- 7713924
TI  - Transmembrane signaling by the alpha subunit of the type I interferon receptor is
      essential for activation of the JAK kinases and the transcriptional factor ISGF3.
AB  - The Type I interferon (IFN) receptor has a multisubunit structure. The component
      of the receptor that has been most thoroughly studied is the alpha subunit.
      Expression of the alpha subunit in mouse L-929 cells confers antiviral response
      to human IFN alpha 8, but not to human IFN alpha 2 or IFN beta. This antiviral
      effect is observed without a significant increase in IFN binding. It has not been
      determined why mouse cells expressing the human alpha subunit show different
      response to the antiviral activity of distinct human Type I IFNs. In this report,
      we demonstrate that the response to human Type I IFNs in mouse cells expressing
      the alpha subunit is dependent on cross-binding to the mouse receptor. This is
      supported by the finding that human IFN alpha 8, but not human IFN alpha 2, cross
      binds to the mouse receptor even in the absence of expression of the human alpha
      subunit. We also demonstrate that only mouse cells expressing the human alpha
      subunit are able to tyrosine-phosphorylate p135tyk2 and JAK-1 and to form the
      ISGF3 complex in response to human IFN alpha 8. These results demonstrate that
      the alpha subunit is essential for IFN alpha signaling through the JAK kinases
      and ISGF3.

PMID- 7713925
TI  - A variant X-linked chronic granulomatous disease patient (X91+) with partially
      functional cytochrome b.
AB  - Genetic analysis of a patient with the variant cytochrome b-245-positive form of
      chronic granulomatous disease revealed a missense mutation resulting in a Arg54-
      >Ser substitution in the gp91phox subunit of cytochrome b-245. As a consequence,
      although no O2- is made, NADPH oxidase-associated FAD accepts electrons from
      NADPH in the cell-free activation system and becomes reduced. The reduced flavin
      exhibits normal levels of iodonitrotetrazolium violet diaphorase activity, and
      the patient's neutrophils exhibit high levels of intracellular oxidant production
      and show a low level of NBT staining in the NBT slide test. Thus, this mutation
      appears to render the heme center of NADPH oxidase present but nonfunctional,
      while leaving the flavin center fully functional.

PMID- 7713926
TI  - Purification and characteristics of the candidate prohormone processing proteases
      PC2 and PC1/3 from bovine adrenal medulla chromaffin granules.
AB  - The prohormone-processing proteases PC1/3 and PC2 belong to the family of
      mammalian subtilisin-related proprotein convertases (PC) possessing homology to
      the yeast Kex2 protease. The presence of PC1/3 and PC2 in secretory vesicles of
      bovine adrenal medulla (chromaffin granules) implicates their role in the
      processing the precursors of enkephalin, neuropeptide Y, somatostatin, and other
      neuropeptides that are present in chromaffin granules. In this study, PC1/3 and
      PC2 were purified to apparent homogeneity from the soluble fraction of chromaffin
      granules by chromatography on concanavalin A-Sepharose, Sephacryl S-200,
      pepstatin A-agarose, and anti-PC1/3 or anti-PC2 immunoaffinity resins. PC1/3 and
      PC2 were monitored during purification by measuring proteolytic activities with
      35S-enkephalin precursor and Boc-Arg-Val-Arg-Arg-methylcoumarin amide (MCA)
      substrates and by following PC1/3 and PC2 immunoreactivity with specific anti
      PC1/3 and anti-PC2 sera generated in this study. Purified PC1/3 and PC2 on SDS
      polyacrylamide gels each show a molecular mass of 66 kDa. PC2 in the soluble
      fraction of chromaffin granules was present at 5- and 10-fold higher enzyme
      protein and activity, respectively, compared with that of PC1/3. PC1/3 and PC2
      cleaved paired basic and monobasic sites within peptide-MCA substrates, with Boc
      Arg-Val-Arg-Arg-MCA and pGlu-Arg-Thr-Lys-Arg-MCA as the most effectively cleaved
      peptides tested. PC1/3 and PC2 showed pH optima of 6.5 and 7.0, respectively.
      Kinetic studies indicated apparent Km values for hydrolysis of Boc-Arg-Val-Arg
      Arg-MCA as 66 and 40 microM, with Vmax values of 255 and 353 nmol/h/mg for PC1/3
      and PC2, respectively. Specificity of the PC enzymes for dibasic sites was
      confirmed by potent inhibition by the active site-directed peptide inhibitors (D
      Tyr)-Glu-Phe-Lys-Arg-CH2Cl and Ac-Arg-Arg-CH2Cl. Inhibition by EGTA and
      activation by Ca2+ indicated PC1/3 and PC2 as Ca(2+)-dependent proteases. In
      addition, PC enzymes were activated by dithiothreitol and inhibited by thiol
      blocking reagents, p-hydroxymercuribenzoate and mercuric chloride. These results
      illustrate the properties of endogenous PC1/3 and PC2 as prohormone-processing
      enzymes.

PMID- 7713927
TI  - Dimerization of HIV-1Lai RNA at low ionic strength. An autocomplementary sequence
      in the 5' leader region is evidenced by an antisense oligonucleotide.
AB  - Genomic human immunodeficiency virus type 1 (HIV-1) RNA consists of two identical
      RNA molecules joined noncovalently near their 5' ends in a region called the
      dimer linkage structure (DLS). Previous work has shown that the putative DLS is
      localized in a 113-nucleotide domain encompassing the 5' end of the gag gene.
      This region contains conserved purine tracks that are thought to mediate
      dimerization through purine quartets. However, recently, an HIV-1Mal RNA
      dimerization model was proposed as the HIV-1Mal RNA dimerization initiation site,
      involving another region upstream from the splice donor site and possibly
      confined within a stem-loop. In the present study, we have investigated the
      dimerization of HIV-1Lai RNA, using in vitro dimerization assays under conditions
      of low ionic strength, predictive RNA secondary structures determined by computer
      folding, and antisense DNA oligonucleotides in order to discriminate between
      these two models. Our results suggest that purine quartets are not involved in
      the dimer structure of HIV-1Lai RNA and have led to the identification of a
      region upstream from the splice donor site. This region, comprising an
      autocomplementary sequence in a possible stem-loop structure, is responsible for
      the formation of dimeric HIV-1Lai RNA.

PMID- 7713929
TI  - The cAMP response element binding protein synergizes with other transcription
      factors to mediate cAMP responsiveness.
AB  - The cAMP responsiveness of the promoter for phosphoenolpyruvate carboxykinase (EC
      4.1.1.32) is mediated by a synergistic interaction between a complex regulatory
      region, which binds liver-enriched transcription factors, and a typical cAMP
      response element (CRE). Although a role for the CRE-binding protein (CREB) in the
      cAMP-responsiveness of this promoter has been generally assumed, some uncertainty
      remains due to the observations that several C/EBP-related proteins bind with
      near equal affinity, relative to CREB, to this particular CRE. Thus, a detailed
      analysis of the involvement of CREB in this synergism was undertaken in HepG2
      cells. Gel mobility shift assays demonstrate that a CRE probe is bound by CREB
      present in HepG2 cells. Furthermore, we show that a dominant repressor of CREB is
      able to significantly reduce the cAMP responsiveness of the PEPCK promoter in
      HepG2 cells. Finally, we demonstrate using a GAL4-CREB fusion protein that CREB
      is able to synergize with the liver-enriched factors bound upstream on the PEPCK
      promoter to mediate a liver-specific response to cAMP. Examination of several
      mutant forms of CREB allow us to conclude that the "synergy" domain of CREB
      resides within amino acid residues 83-203, and that residues 83-145 can mediate a
      partial synergistic response. This study establishes that CREB is able to
      synergize with liver-enriched transcription factors to mediate a tissue-specific
      response to cAMP.

PMID- 7713928
TI  - The gastrin-releasing peptide receptor is rapidly phosphorylated by a kinase
      other than protein kinase C after exposure to agonist.
AB  - Several guanine nucleotide-binding protein-coupled receptors are known to be
      rapidly phosphorylated after agonist exposure. In this study we show that the
      gastrin-releasing peptide receptor (GRP-R) is rapidly phosphorylated in response
      to agonist exposure. When [32P]orthophosphate-labeled cells were exposed to
      bombesin, the receptor was maximally phosphorylated on serine and threonine
      residues within 1 min. Although addition of 12-O-tetradecanoylphorbol 13-acetate
      also resulted in phosphorylation of the GRP-R, elimination of protein kinase C
      activity using the inhibitor 7-hydroxystaurosporine did not prevent bombesin
      induced GRP-R phosphorylation. We conclude that a kinase other than protein
      kinase C is principally responsible for the rapid, agonist-induced
      phosphorylation of the GRP-R.

PMID- 7713930
TI  - Cellubrevin is a resident protein of insulin-sensitive GLUT4 glucose transporter
      vesicles in 3T3-L1 adipocytes.
AB  - Insulin stimulates glucose transport in muscle and fat cells by inducing
      translocation of GLUT4 glucose transporters from a storage site to the cell
      surface. The mechanism of this translocation and the identity of the storage site
      are unknown, but it has been hypothesized that transporters recycle between an
      insulin-sensitive pool, endosomes, and the cell surface. Upon cell homogenization
      and fractionation, the storage site migrates with light microsomes (LDM) separate
      from the plasma membrane fraction (PM). Cellubrevin is a recently identified
      endosomal protein that may be involved in the reexocytosis of recycling
      endosomes. Here we describe that cellubrevin is expressed in 3T3-L1 adipocytes
      and is more abundant in the LDM than in the PM. Cellubrevin was markedly induced
      during differentiation of 3T3-L1 fibroblasts into adipocytes, in parallel with
      GLUT4, and the development of insulin regulated traffic. In response to insulin,
      the cellubrevin content decreased in the LDM and increased in the PM, suggesting
      translocation akin to that of the GLUT4 glucose transporter. Vesicle-associated
      membrane protein 2 (VAMP-2)/synaptobrevin-II, a protein associated with regulated
      exocytosis in secretory cells, also redistributed in response to insulin. Both
      cellubrevin and VAMP-2 were susceptible to cleavage by tetanus toxin.
      Immunopurified GLUT4-containing vesicles contained cellubrevin and VAMP-2, and
      immunopurified cellubrevin-containing vesicles contained GLUT4 protein, but
      undiscernible amounts of VAMP-2. These observations suggest that cellubrevin and
      VAMP-2 are constituents of the insulin-regulated pathway of membrane traffic.
      These results are the first demonstration that cellubrevin is present in a
      regulated intracellular compartment. We hypothesize that cellubrevin and VAMP-2
      may be present in different subsets of GLUT4-containing vesicles.

PMID- 7713932
TI  - Glycosylation of human truncated Fc epsilon RI alpha chain is necessary for
      efficient folding in the endoplasmic reticulum.
AB  - The high affinity immunoglobulin E (IgE) receptor is an alpha beta gamma 2
      tetrameric complex. The truncated extracellular segment (alpha t) of the heavily
      glycosylated alpha chain is sufficient for high affinity binding of IgE. Here we
      have expressed various alpha t mutants in eukaryotic and prokaryotic cells to
      analyze the role of glycosylation in the folding, stability, and secretion of
      alpha t. All seven N-linked glycosylation sites in alpha t are glycosylated and
      their mutations have an additive effect on the folding and secretion of alpha t.
      Mutation of the seven N-glycosylation sites (delta 1-7 alpha t) induces
      misfolding and retention of alpha t in the endoplasmic reticulum. Similarly,
      tunicamycin treatment reduces substantially the folding efficiency of wild-type
      alpha t. In contrast, no difference in folding efficiency is detected between
      wild-type alpha t and delta 1-7 alpha t expressed in Escherichia coli. In
      addition, maturation of N-linked oligosaccharides and addition of O-linked
      carbohydrates are not required for either the transport or the IgE-binding
      function of alpha t. Furthermore, complete enzymatic deglycosylation does not
      affect the stability and the IgE-binding capacity of alpha t. Therefore,
      glycosylation is not intrinsically necessary for proper folding of alpha t but is
      required for folding in the endoplasmic reticulum. Our data are compatible with
      the concept that specific interactions between N-linked oligosaccharides and the
      folding machinery of the endoplasmic reticulum are necessary for efficient
      folding of alpha t in eukaryotic cells.

PMID- 7713931
TI  - Targeted melting and binding of a DNA regulatory element by a transactivator of c
      myc.
AB  - A far upstream element (FUSE) of c-myc stimulates promoter activity when bound by
      a newly identified trans-acting protein, which is expressed in cycling cells.
      Since FUSE binding protein (FBP) binds only the noncoding strand (NCS) of its
      regulatory element in a sequence-specific manner, and not double-stranded (ds)
      DNA, formation of the protein DNA complex in vivo first requires unwinding of the
      DNA helix. In this report, we show evidence that FBP forces strand separation of
      short stretches of linear dsDNA. Because FUSE is contained within a region of
      helical instability that is partially unwound in negatively supercoiled DNA, it
      is a target for more extensive duplex strand separation by FBP, which first
      exposes and then selectively binds its NCS cognate sequence. In contrast, other
      single-stranded DNA binding proteins (SSBs) do not demonstrate this FUSE
      targeting activity. The novel linkage of regional dsDNA melting with cis-element
      binding by a transcriptional activator has broad implications in the regulation
      of eukaryotic gene expression.

PMID- 7713934
TI  - Characterization of a gp91-phox promoter element that is required for interferon
      gamma-induced transcription.
AB  - The cytochrome b558 heavy chain (gp91-phox) is expressed nearly exclusively in
      terminally differentiating myelomonocytic cells, thereby providing a model to
      study the events of late myeloid differentiation. We describe a tissue culture
      assay for studying interferon gamma induction of gp91-phox expression and a cis
      element in the gp91-phox promoter that is necessary but not sufficient for this
      activity. In vitro assays reveal two DNA-binding proteins that interact with this
      cis-element. One factor is restricted to hematopoietic cells, is required for an
      interferon gamma response, and binds to an element similar to the Ets protein
      family consensus, although it does not correspond to known family members. The
      second factor is the ubiquitous CCAAT-binding protein CP1, which is dispensable
      for an interferon gamma response. Single base pair mutations in the gp91-phox
      promoter that specifically abolish the binding of the hematopoietic-associated
      factor have previously been identified in chronic granulomatous disease patients
      (Newburger, P. E., Skalnik, D. G., Hopkins, P. J., Eklund, E. A., and Curnutte,
      J. T. (1994) J. Clin. Invest. 94, 1205-1211). The data reported here directly
      demonstrate the functional significance of the hematopoietic-associated factor
      for gp91-phox promoter activity and reveal the binding properties and tissue
      distribution of this novel DNA-binding protein.

PMID- 7713933
TI  - Functional characterization of the brain-specific FGF-1 promoter, FGF-1.B.
AB  - Expression of alternatively spliced human FGF-1 (or aFGF) transcripts is
      regulated in a tissue-specific manner via multiple promoters. To identify the cis
      regulatory elements in the brain-specific FGF-1.B promoter, we constructed a
      series of promoter deletions fused to the luciferase reporter gene and
      transfected into an FGF-1.B positive glioblastoma cell line, U1240MG, and a 1.B
      negative cell line, U1242MG. Results of transient transfections indicate three
      elements that are involved in the positive regulation of FGF-1.B expression. The
      core promoter is located in a 40-base pair region (between -92 and -49), and two
      regulatory regions (RR-1 and RR-2) are located within the 540-base pair region 5'
      to the major transcription start site (defined as +1). Electrophoretic mobility
      shift assays and footprinting analysis have identified sequence-specific binding
      sites in RR-1 and RR-2. Mutants of RR-2 abolished binding to nuclear proteins and
      showed diminished luciferase reporter activity. The effects seen are specific for
      the U1240MG cell line, supporting a role for RR-2 in the tissue-specific
      regulation of FGF-1.B. Southwestern analysis using an oligonucleotide probe
      derived from RR-2 (nucleotides -489 to -467) further identified a 37-kDa protein
      that is present in nuclear extracts from U1240MG and brain but not from U1242MG.

PMID- 7713935
TI  - Inactive type II and type I receptors for TGF beta are dominant inhibitors of TGF
      beta-dependent transcription.
AB  - Although transforming growth factor-beta (TGF beta) is implicated in
      differentiation and disease, proof of in vivo function requires specific
      inhibitors of the TGF beta cascade. TGF beta binds a family of type I and type II
      receptors (T beta RI, T beta RII), containing a cytoplasmic serine/threonine
      kinase domain. We previously reported that kinase-deficient T beta RII (delta kT
      beta RII) blocks TGF beta-dependent transcription in cardiac myocytes. It is
      controversial whether both receptors are needed in all cells for gene regulation
      by TGF beta or whether they mediate distinct subsets of TGF beta-dependent
      events. To resolve this uncertainty, TGF beta-dependent transcription was
      investigated in cardiac myocytes versus mink lung epithelial cells. 1) delta kT
      beta RII inhibits induction of a TGF beta-responsive reporter gene, in both cell
      backgrounds. 2) Charged-to-alanine mutations of key residues of the T beta RII
      kinase, including consensus ATP binding and amino acid recognition motifs, are
      competent for binding but not transcriptional activation. Each inactive receptor
      inhibits TGF beta-dependent transcription in both cell types. 3) Kinase-deficient
      T beta RI (delta kT beta RI) likewise impairs TGF beta-dependent transcription,
      less completely than delta kT beta RII; kinase-deficient activin type I receptor
      has no effect. 4) TGF beta-binding proteins in cardiac cells and Mv1Lu cells are
      comparable by affinity labeling and immunoprecipitation; however, Mv1Lu cells
      express up to 3-fold higher levels of T beta RII and T beta RI. Thus, the model
      inferred from TGF beta-resistant cell lines (that T beta RII and T beta RI are
      necessary in tandem for the TGF beta-signaling complex to regulate transcription)
      is valid for cardiac myocytes, the cell type most prominently affected in TGF
      beta-deficient animals.

PMID- 7713936
TI  - Transcriptional activation of the Escherichia coli adaptive response gene aidB is
      mediated by binding of methylated Ada protein. Evidence for a new consensus
      sequence for Ada-binding sites.
AB  - The Escherichia coli aidB gene is part of the adaptive response to DNA
      methylation damage. Genes belonging to the adaptive response are positively
      regulated by the ada gene; the Ada protein acts as a transcriptional activator
      when methylated in one of its cysteine residues at position 69. Through DNaseI
      protection assays, we show that methylated Ada (meAda) is able to bind a DNA
      sequence between 40 and 60 base pairs upstream of the aidB transcriptional
      startpoint. Binding of meAda is necessary to activate transcription of the
      adaptive response genes; accordingly, in vitro transcription of aidB is dependent
      on the presence of meAda. Unmethylated Ada protein shows no protection against
      DNaseI digestion in the aidB promoter region nor does it promote aidB in vitro
      transcription. The aidB Ada-binding site shows only weak homology to the proposed
      consensus sequences for Ada-binding sites in E. coli (AAANNAA and AAAGCGCA) but
      shares a higher degree of similarity with the Ada-binding regions from other
      bacterial species, such as Salmonella typhimurium and Bacillus subtilis. Based on
      the comparison of five different Ada-dependent promoter regions, we suggest that
      a possible recognition sequence for meAda might be AATnnnnnnG-CAA. Higher
      concentrations of Ada are required for the binding of aidB than for the ada
      promoter, suggesting lower affinity of the protein for the aidB Ada-binding site.
      Common features in the Ada-binding regions of ada and aidB are a high A/T
      content, the presence of an inverted repeat structure, and their position
      relative to the transcriptional start site. We propose that these elements, in
      addition to the proposed recognition sequence, are important for binding of the
      Ada protein.

PMID- 7713937
TI  - Regulation of rDNA transcription factors during cardiomyocyte hypertrophy induced
      by adrenergic agents.
AB  - Ribosomal DNA transcription is important to the regulation of cardiomyocyte
      ribosome content and, as a consequence, the rate of protein synthesis and
      accumulation during cardiac hypertrophy. We studied the regulation of ribosomal
      RNA synthesis and the levels of RNA polymerase I and the ribosomal DNA
      transcription factor, UBF, during norepinephrine-induced hypertrophy of
      contraction-arrested neonatal cardiomyocytes in culture. Nuclear run-on assays
      and Western blots demonstrated that, concomitant with hypertrophy, norepinephrine
      (1 microM) increased the rate of ribosomal DNA transcription, without causing an
      increase in the amount of RNA polymerase I. However, the elevated rate of rRNA
      synthesis was accompanied by an increased cellular content of UBF protein as
      determined by Western analysis. Northern blots demonstrated norepinephrine
      induced increases in UBF mRNA in neonatal cardiomyocytes indicating that the
      response was regulated, at least in part, at the pretranslational stage. Both
      alpha- and beta-adrenergic agents increased the level of UBF mRNA. The beta
      adrenergic response was mimicked by forskolin (1 microM) and the cyclic AMP
      analog dibutyryl cAMP (10 microM). However, activation of protein kinase C by
      phorbol 12-myristate 13-acetate (0.1 microM) did not increase expression of UBF.
      These results implicate UBF as a possible regulatory factor of the accelerated
      rDNA transcription observed during norepinephrine-mediated cardiomyocyte
      hypertrophy.

PMID- 7713938
TI  - The action of interleukin-2 receptor subunits defines a new type of signaling
      mechanism for hematopoietin receptors in hepatic cells and fibroblasts.
AB  - The gene regulatory functions of the human IL-2 receptor (IL-2R) were
      reconstituted in transiently transfected hepatoma cells. The combination of IL-2R
      beta and -gamma mediated a strong stimulation via the cytokine response element
      of the alpha 1-acid glycoprotein gene and the hematopoietin receptor response
      element, but none via the IL-6 response element or the sis-inducible element. IL
      2R alpha enhanced 10-fold the sensitivity of the IL-2R beta.gamma complex to
      respond to IL-2 or IL-15, but did not modify the specificity or the magnitude of
      maximal gene regulation. A homodimerizing chimeric receptor G-CSFR-IL-2R beta
      could mimic the IL-2R action. The IL-2R-mediated gene regulation was similar to
      that seen with receptors for IL-4 and IL-7, but differed from that for IL-6 type
      cytokines, thrombopoietin, erythropoietin, and growth hormone. The activation of
      STAT proteins by the IL-2R was assessed in transfected L-cells and COS-1 cells.
      Although IL-2R subunits were highly expressed in these cells, no STAT protein
      activation was detectable. Transient overexpression of JAK3 was unable to change
      the signaling specificity of the hematopoietin receptors in rat hepatoma, L-, and
      COS cells, but established a prominent activation of the IL-6 response elements
      by the IL-2R and IL-4R in HepG2 cells. The data support the model that the IL-2R
      and related hematopoietin receptors produce at least two separate signals which
      control gene expression.

PMID- 7713939
TI  - Characterization of a protein kinase C-delta (PKC-delta) ATP binding mutant. An
      inactive enzyme that competitively inhibits wild type PKC-delta enzymatic
      activity.
AB  - To investigate the function of protein kinase C (PKC)-delta, we mutated its ATP
      binding site by converting the invariant lysine in the catalytic domain (amino
      acid 376) to an arginine. Expression vectors containing wild type and mutant PKC
      delta cDNAs were generated either with or without an influenza virus
      hemagglutinin epitope tag. After expression in 32D cells by transfection, the PKC
      delta ATP binding mutant (PKC-delta K376R) was not able to phosphorylate itself
      or the PKC-delta pseudosubstrate region-derived substrate, indicating that PKC
      delta K376R was an inactive enzyme. PKC activity was inhibited by 67% in 32D
      cells coexpressing both PKC-delta wild type (PKC-delta WT) and PKC-delta K376R
      when compared to 32D cells expressing only PKC-delta WT. Mixture of PKC-delta WT
      and PKC-delta K376R kinase sources in vitro also reduced the enzymatic activity
      of PKC-delta WT. These results suggest that PKC-delta K376R competes with PKC
      delta WT and inhibits PKC-delta WT phosphorylation of its in vitro substrate.
      While PKC-delta WT overexpressed in 32D cells demonstrated 12-O
      tetradecanoylphorbol-13-acetate (TPA)-dependent translocation from the cytosolic
      to the membrane fraction, PKC-delta K376R was exclusively localized in the
      membrane fraction even prior to TPA stimulation. Unlike PKC-delta WT which was
      phosphorylated on tyrosine residue(s) only after TPA treatment, PKC-delta K376R
      was constitutively phosphorylated on tyrosine residue(s). Although exposure of
      PKC-delta WT transfectants to TPA induced 32D monocytic differentiation, the
      32D/PKC-delta K376R transfectants were resistant to TPA-induced differentiation.
      Thus, expression of active PKC-delta is required to mediate 32D monocytic
      differentiation in response to TPA stimulation.

PMID- 7713940
TI  - Structure and function of the UvrB protein.
AB  - UvrB plays a central role in (A)BC excinuclease. To identify the regions of UvrB
      which are involved in interacting with UvrA, UvrC, and DNA, deletion mutants,
      point mutants, and various fusion forms of UvrB were constructed and
      characterized. We found that the region encompassing amino acid residues 115-250
      of UvrB binds to UvrA, while the region encompassing amino acid residues 547-673
      binds to both UvrA and UvrC. In addition, the region between these two domains,
      which contains the helicase motifs II-VI, was found to be involved in binding to
      DNA. Within this DNA-binding region, two point mutants, E265A and E338A, were
      found to be unable to bind DNA while two residues, Phe-365 and Phe-496, were
      identified to interact with DNA. Furthermore, fluorescence quenching studies with
      mutants F365W and F496W and repair of thymine cyclobutane dimers by photoinduced
      electron transfer by these mutants suggest that residues Phe-365 and Phe-496
      interact with DNA most likely through stacking interactions.

PMID- 7713941
TI  - Simultaneous detection of free radical release and membrane current during
      phagocytosis.
AB  - Stimulation of macrophages induces the "respiratory burst" response which is
      associated with the generation of superoxide (O2-), a drop in cytoplasmic pH, and
      a pronounced depolarization of the membrane potential. The purpose of the present
      studies was to determine whether an increase in O2- was temporally related to
      changes in membrane potential and transmembrane current. Release of O2- at the
      single cell level was photometrically monitored during phagocytosis of immune
      complexes while simultaneously measuring whole-cell current. Membrane
      depolarization and the generation of a non-selective current followed an increase
      in O2- production with a variable lag time which was correlated with the state of
      cellular maturation in culture. In the absence of phagocytosis, the exposure of
      macrophages to O2- generated by a xanthine-xanthine oxidase reaction activated a
      non-selective current similar to that seen after phagocytosis. These results
      provide the first demonstration of the relationship between free radical release
      and the ensuing electrophysiological signaling events which are linked to
      particle engulfment in phagocytic cells.

PMID- 7713942
TI  - Tyrosine phosphorylation-dependent stimulation of amyloid precursor protein
      secretion by the m3 muscarinic acetylcholine receptor.
AB  - Stimulation of m1 and m3 muscarinic acetylcholine receptors, which are coupled to
      phosphoinositide hydrolysis and protein kinase C activation, has been shown to
      increase the release of soluble amyloid precursor protein derivatives (APPs). The
      effect is mimicked by phorbol esters, which directly activate protein kinase C.
      Using human embryonic kidney cells expressing individual muscarinic receptor
      subtypes, we found that stimulation of APPs release by the muscarinic agonist
      carbachol was only partially reduced by a specific inhibitor of protein kinase C
      (the bisindolylmaleimide GF 109203X), while the response to phorbol 12-myristate
      13-acetate (PMA) was abolished. The increase in APPs release elicited by
      carbachol and PMA was accompanied by elevated tyrosine phosphorylation of several
      proteins and reduced by tyrosine kinase inhibitors; GF 109203X significantly
      reduced the stimulation of tyrosine phosphorylation by carbachol and PMA.
      Inhibition of protein tyrosine phosphatases by vanadyl hydroperoxide markedly
      increased cellular tyrosine phosphorylation and enhanced APPs release as
      effectively as PMA and carbachol. Direct phosphorylation of amyloid precursor
      protein on tyrosine residues following treatment with carbachol, PMA, or vanadyl
      hydroperoxide was not observed. The results implicate both tyrosine
      phosphorylation and protein kinase C-dependent mechanisms in the regulation of
      APPs release by G protein-coupled receptors, and suggest that carbachol and PMA
      increase APPs release from human embryonic kidney cells expressing m3 muscarinic
      receptors via partially divergent pathways that converge at a tyrosine
      phosphorylation-dependent step.

PMID- 7713943
TI  - Quaternary structure of casein kinase 2. Characterization of multiple oligomeric
      states and relation with its catalytic activity.
AB  - The structure-activity relationship of casein kinase 2 (CK2) was examined with
      regard to its previously reported property to self-aggregate in vitro.
      Sedimentation velocity and electron microscopy studies showed that the purified
      kinase exhibited four major, different oligomeric forms in aqueous solution. This
      self-polymerization was a reproducible and fully reversible process, highly
      dependent upon the ionic strength of the medium, suggesting that electrostatic
      interactions are mostly involved. At high salt concentrations (e.g. 0.5 M NaCl),
      CK2 appears as spherical moieties with a 18.7 +/- 1.6 nm average diameter,
      roughly corresponding to the alpha 2 beta 2 protomer, as deduced by measurements
      of the Stokes radius and by light scattering studies. At lower ionic strength
      (e.g. 0.2 M NaCl), the protomers associate to form ring-like structures with a
      diameter (averaging 36.6 +/- 2.1 nm) and Stokes radius indicating that they are
      most likely made of four circularly associated alpha 2 beta 2 protomers. At 0.1 M
      NaCl, two additional polymeric structures were visualized: thin filaments (16.4
      +/- 1.4 nm average), as long as 1 to 5 microns, and thick and shorter filaments
      (28.5 +/- 1.6 nm average). Examination of the molecular organization of CK2 under
      different catalytic conditions revealed that the ring-like structure is the
      favored conformation adopted by the enzyme in the presence of saturating
      concentrations of substrates and cofactors. During catalysis, well-known
      cofactors like MgCl2 or spermine are the main factors governing the stabilization
      of the active ring-like structure. On the other hand, inhibitory high salt
      concentrations promote the dissociation of the active ring-like structure into
      protomers. Such observations suggest a strong correlation between the ring-like
      conformation of the enzyme and optimal specific activity. Thus, CK2 may be
      considered as an associating-dissociating enzyme, and this remarkable property
      supports the hypothesis of a cooperative and allosteric regulation of the kinase
      in response to appropriate regulatory ligands possibly taking place in intact
      cells.

PMID- 7713944
TI  - Interaction of EF-C/RFX-1 with the inverted repeat of viral enhancer regions is
      required for transactivation.
AB  - The hepatitis B virus (HBV) and polyomavirus (Py) enhancer regions contain
      multiple cis-acting elements that contribute to enhancer activity. The EF-C
      binding site was previously shown to be an important functional component of each
      enhancer region. EF-C is a ubiquitous binding activity that interacts with an
      inverted repeat sequence in the HBV and Py enhancer regions. Although the EF-C
      binding site is required for optimal enhancer function, the EF-C site does not
      possess intrinsic enhancer activity when assayed in the absence of flanking
      elements. With both the HBV and Py enhancer regions, EF-C stimulates the activity
      of adjacent enhancer elements in a synergistic manner. EF-C corresponds to RFX-1,
      a protein that binds to a conserved and functionally important site in major
      histocompatibility complex (MHC) class II antigen promoter regions.
      Interestingly, the RFX-1 binding site in MHC class II promoters only contains an
      EF-C half-site, maintaining one arm of the inverted repeat in an EF-C binding
      site. We have investigated the binding of purified EF-C and RFX-1 to sites in the
      Py and HBV enhancer regions that carry mutations that either disrupt one arm of
      the EF-C inverted repeat, or alter the spacing between the repeats. Our results
      show that the interaction of EF-C and RFX-1 with an intact inverted repeat is
      required for functional activity of these viral enhancer regions. Chemical
      footprinting and modification interference assays show that the interaction of EF
      C and RFX-1 with the DRA MHC class II promoter truly represents half-site
      interaction, and that this binding is unstable. In contrast, the binding of EF-C
      and RFX-1 to the viral inverted repeats is stable. These results suggest that an
      additional activity may be required to stabilize EF-C/RFX-1 interaction with the
      MHC class II promoter, and that viral enhancer regions have evolved high affinity
      binding sites to sequester dimeric EF-C/RFX-1.

PMID- 7713945
TI  - Inhibitory effect of a conjugate between human urokinase and urinary trypsin
      inhibitor on tumor cell invasion in vitro.
AB  - Proteolytic enzymes such as urokinase-type plasminogen activator (uPA), plasmin,
      and collagenase mediate proteolysis by a variety of tumor cells. uPA secreted by
      tumor cells can be bound to a cell surface receptor via a growth factor-like
      domain within the amino-terminal fragment (ATF) of the uPA molecule with high
      affinity. Urinary trypsin inhibitor (UTI) efficiently inhibits the soluble and
      the tumor cell-surface receptor-bound plasmin and subsequently reduces tumor cell
      invasion and the formation of metastasis. The anti-invasive effect is dependent
      on the anti-plasmin activity of the UTI molecule, domain II in particular. We
      synthesized a conjugate between ATF of human uPA and a native UTI molecule or
      domain II of UTI (HI-8). The effect of the conjugates (ATF.UTI or ATF.HI-8) on
      tumor cell invasion in vitro was investigated. ATF.UTI and ATF.HI-8 bound to U937
      cells in a rapid, saturable, dose-dependent, and reversible manner. A large part
      of receptor-bound ATF-UTI and ATF.HI-8 remains on the cell surface for at least 5
      h at 37 degrees C. Inhibition of tumor cell-surface receptor-bound plasmin by
      ATF.UTI and ATF.HI-8 was markedly enhanced when compared with tumor cells treated
      either with ATF, UTI, or HI-8. Results of a cell invasion assay showed that
      ATF.UTI and ATF.HI-8 is very effective at targeting HI-8 specifically to uPA
      receptor-expressing tumor cells, whereas tumor cells devoid of uPA receptor may
      be less affected by the conjugates. Our results indicate that cell surface uPA
      and plasmin activity is essential to the invasive process and that the conjugates
      exhibit plasmin inhibition to the close environment of the cell surface and
      subsequently inhibit the tumor cell invasion through Matrigel in an in vitro
      invasion assay.

PMID- 7713946
TI  - Post-translational and activation-dependent modifications of the G protein
      coupled thrombin receptor.
AB  - The purpose of the present study was to analyze the post-translational and
      activation-dependent modifications of the G protein-coupled thrombin receptor. A
      human receptor cDNA was engineered to encode an epitope tag derived from the
      vesicular stomatitis virus glycoprotein at the COOH terminus of the receptor and
      expressed in human embryonic kidney 293 cells. We show here that the mature
      receptor is a glycosylated protein with an apparent molecular mass ranging from
      68 to 80 kDa by SDS-polyacrylamide gel electrophoresis. Removal of asparagine
      linked oligosaccharides with N-glycosidase F leads to the appearance of a 36-40
      kDa receptor species. The current model for receptor activation by thrombin
      involves specific hydrolysis of the arginine-41/serine-42 (Arg-41/Ser-42) peptide
      bond. Cleavage of the receptor by thrombin was demonstrated directly by Western
      analyses performed on membranes and glycoprotein-enriched lysates from
      transfected cells. Whereas thrombin treatment of cells results in increased
      mobility of the receptor in SDS-polyacrylamide gel electrophoresis, we found that
      their treatment with the thrombin receptor agonist peptide leads to a decrease in
      thrombin receptor mobility due, in part, to phosphorylation. The serine proteases
      trypsin and plasmin also cleave and activate the receptor similar to thrombin,
      whereas chymotrypsin cleaves the receptor at a site distal to Arg-41, thus
      rendering it unresponsive to thrombin while still responsive to thrombin receptor
      agonist peptide.

PMID- 7713947
TI  - Distinguishing wear and creep in clinically retrieved polyethylene inserts.
AB  - There is an increasing awareness of the clinical problems associated with ultra
      high-molecular-weight polyethylene (UHMWPE) wear and failure in orthopedics. To
      better understand the reasons for wear and failure, methods were developed using
      polarized light microscopic analysis and backscattered electron (BSE) imaging
      with correlated elemental analysis to distinguish the contributions of wear,
      creep, and third-body particulate. This study determined that microscopic metal
      particles (< 10 microns) previously not observed with the stereomicroscope could
      be easily observed with the BSE technique. BSE imaging identified embedded metal
      in 5/5 of the tibial and 2/4 of the acetabular inserts, which were thought to be
      free of metal debris after stereoscopic examination. Correlated elemental
      analysis showed that the microscopic particles could be traced to the elements
      known to be present in the porous coatings of the retrieved uncemented implants.
      Creep was distinguished from wear in the total hip and total knee inserts by
      using polarized light microscopic techniques. Continued development of polarized
      light microscopic techniques applied in this investigation should assist
      biomaterials experts in the future to better distinguish wear and creep in
      retrieved clinical inserts. The correlated BSE and elemental analysis will assist
      in determining the roll of microscopic third-body particular in wear and
      osteolysis in total joint replacement.

PMID- 7713948
TI  - Simple technique for the preparation of silicone gel particles: the effect of
      silicone gel particles on oxidative responses of macrophages.
AB  - A simple technique was developed to prepare phagocytosable-size particles from
      the silicone gel used in breast implants. Sonication of silicone gel (1 g) in 5
      ml of 20 mM sodium phosphate buffer (pH 7.2) containing 1% (wt/vol)
      polyoxypropylene-polyethylene block surfactant (F-68 or F-108) produced silicone
      gel particles ranging from 1-50 microns in diameter. Passage of the suspension
      through a series of filters yielded phagocytosable particles (1-5 microns in
      diameter) at a concentration of ca. 2 x 10(9) particles/ml. The particles
      remained as individual particles, did not coalesce to form large clumps, and were
      not pelleted by centrifugation (2000 x g, 20 min). They were not toxic for rabbit
      alveolar macrophages (AM) during 24 h of incubation at 37 degrees C, did not
      elicit an oxidative burst from AM in vitro in a luminol-enhanced chemiluminescent
      assay, and did not significantly increase the phorbol myristate acetate (PMA)
      elicited oxidative burst by AM. AM isolated from rabbits 2 days after the
      intravenous injection of silicone particles were not primed or activated (i.e.,
      the AM did not show an enhanced oxidative burst when elicited with PMA in vitro).
      However, AM isolated from rabbits 2 days after intratracheal injection of the
      particles were primed but only exhibited a 4-6-fold increase in the oxidative
      burst elicited with PMA.

PMID- 7713949
TI  - Effects of a structural change in collagen upon binding to conditioned dentin
      studied by 13C NMR.
AB  - To develop a better adhesive functional monomer, it is imperative to understand
      the adhesion mechanisms of the resin to the dentin surface. Bond strength to the
      decalcified dentin surface pretreated with dentin primer, an aqueous ethanol
      solution of N-methacryloyl glycine, increases by increasing the water content in
      the primer. The aqueous primer could increase the thickness of the hybrid layer.
      The structural change of dentinal collagen with NM alpha A was studied by using a
      model compound for collagen,--(1Pro-2Pro-3Gly)10--, by 13C nuclear magnetic
      resonance (NMR). The model compound was aggregated in ethanol but dissociated in
      water. It was found that NM alpha A effectively dissociated the aggregated model
      compound in water. The dissociation of decalcified dentin was essential to create
      a thick hybrid layer that could afford a higher bond strength to dentin.

PMID- 7713950
TI  - Studies on the tumor-promoting activity of biomaterials: inhibition of metabolic
      cooperation by polyetherurethane and silicone.
AB  - When V79 metabolic cooperation (MC) assay was performed to detect tumor-promoting
      activities, inhibitory activities on the gap-junctional intercellular
      communication were first detected in both extracts prepared from
      polyetherurethane (PEU) and silicone. The former inhibited more strongly than the
      latter. Furthermore, the lowest effective concentrations in MC assay correlated
      well with the values of the total active incidences obtained by histologic
      evaluation of the 2-year implantation test in rats. Poly(tetramethylene oxide)
      (PTMO) showed the highest inhibitory activities among the constituents of PU.
      Thus, the shorter the chain length of PTMO, the stronger the inhibitory
      activities of PTMO in MC assay. PTMO moiety may play an important role in the
      tumor-promotion stage during tumorigenesis induced by PU.

PMID- 7713951
TI  - Studies on the tumor-promoting activity of additives in biomaterials: inhibition
      of metabolic cooperation by phenolic antioxidants involved in rubber materials.
AB  - For the detection of tumor-promoting activities of phenolic antioxidants, the
      inhibitory activities on the intercellular gap-junctional communication were
      investigated using the V79 metabolic cooperation (MC) assay. Among eight
      antioxidants, 4,4'-butylidene-bis(3-methyl-6-tert-butyl-phenol), 2,2'-methylene
      bis(4-methyl-6-tert-butylphenol) (MBMBP), and styrenated phenol (SP) showed
      stronger inhibitory activities than lithocholic acid, which is known to be a
      tumor promotor. However, 4,4'-thio-bis(3-methyl-6-tert-butylphenol), Irganox
      1010, and 1330 did not inhibit at any concentrations. When the single-electron
      oxidation potentials were compared among antioxidants, the electrochemical ease
      estimated with the first oxidation potential was correlated with the cytotoxic
      potentials (r = 0.88), but not with the inhibitory activities in an MC assay. The
      tumor-promoting activity of MBMBP was also investigated using an in vitro, two
      stage Balb/c 3T3 transformation assay. MBMBP did not show initiating activity,
      but significant promoting activity at concentrations of both 1 and 2.5
      micrograms/ml were noted. These concentrations were close to the lowest effective
      inhibitory concentration (1.3 micrograms/ml) of MBMBP in an MC assay. In
      conclusion, there is a possibility that the phenolic antioxidants that show
      inhibitory activities in an MC assay contribute to the enhancement of tumor
      incidence induced by biomaterials.

PMID- 7713952
TI  - Isolation of predominantly submicron-sized UHMWPE wear particles from
      periprosthetic tissues.
AB  - A method of tissue digestion using sodium hydroxide was applied to the isolation
      and recovery of ultra-high-molecular-weight polyethylene (UHMWPE) particles from
      tissues around failed total hip replacements. Density gradient
      ultracentrifugation of the digested tissues was performed to separate the UHMWPE
      from cell debris and other particulates. Fourier transform infrared spectroscopy
      and differential scanning calorimetry (DSC) verified that the recovered particles
      were UHMWPE. When viewed by scanning electron microscopy, individual particles
      were clearly observed and were either rounded or elongated. The majority were
      submicron in size. The application of this method to the study of particles from
      periprosthetic tissues may elucidate aspects of biomaterial particle size and
      shape that are important to the biologic response to, and clinical outcome of,
      total joint replacement.

PMID- 7713953
TI  - Influence of implant location on the mechanical characteristics using the
      transcortical model.
AB  - Mechanical evaluation of implants harvested following surgical implantation is
      often performed as part of the screening process for new materials or surface
      textures. The question of randomization with respect to implant placement often
      arises when attempting to design a study to evaluate several implant types, while
      minimizing the number of animals required to perform the investigation. The
      purpose of this study was to analyze the effects of implant placement within the
      canine femur on mechanical characteristics of the bone-implant interface when
      using the transcortical model. Both smooth and porous-surfaced implants were
      evaluated at several time periods to determine the effects of placement in the
      medial versus left cortex, proximal versus distal placement, and left versus
      right femur. The smooth-surfaced implants demonstrated a significant effect due
      to proximal versus distal placement within the femur only. There were no other
      significant comparisons. Porous-surfaced implants demonstrated no significant
      effects due to placement within the femur. The results demonstrate the necessity
      for careful study design when evaluating smooth surfaced implants; however,
      paired comparisons in either the medial versus lateral cortex or left versus
      right femur will provide unbiased comparisons between the implants.

PMID- 7713954
TI  - Comparison of bone-implant interface shear strength of hydroxyapatite-coated and
      alumina-coated metal implants.
AB  - We performed a transcortical push-out test to determine the effect of surface
      roughness of hydroxyapatite (HA)-coated implants on bone-implant shear strength
      in a canine model. Hydroxyapatite- and alumina-coated SUS316L with the same
      surface roughness (roughness average: Ra = 5 microns) and HA-coated Ti-6A1-4V (Ra
      = 8.4 microns), sintered HA (Ra = 0.9 micron), and dense alumina (Ra = 1.3
      microns) were inserted into the dog's femur. The interface shear strength of the
      dense alumina was significantly lower than that of other implants at both 4 and
      12 weeks after implantation. At 4 weeks after implantation, the interface shear
      strength of the alumina-coated SUS316L was significantly lower than that of other
      implants (P < .05) except the dense alumina, but at 12 weeks, there was no
      significant difference between the implant types except the dense alumina. This
      indicates that the surface roughness of the HA coating affects the enhancement of
      the bone-implant interface shear strength at the early period after implantation,
      and that a surface roughness of several micrometers does not influence the bond
      strength between bone and HA. A scanning electron microscopic study indicated
      that in almost all cases at 12 weeks, the failure site after push-out testing was
      the coating-substrate interface, not the coating-bone interface. Therefore,
      protection of the coating-substrate interface from direct shear loading is
      needed.

PMID- 7713955
TI  - Effect of particle size of metastable calcium phosphates on mechanical strength
      of a novel self-setting bioactive calcium phosphate cement.
AB  - Resistance to compressive strength after setting of the calcium phosphate cement
      consisting of tetracalcium phosphate (TECP), dicalcium phosphate dihydrate
      (DCPD), and 40 wt/wt% of a synthetic hydroxyapatite (HAP) was tested. An
      equimolar mixture of the calcium phosphate powder containing DCPD (particle
      diameter [D] 0.52-3.33 microns) and TECP (D, 1.1-13.1 microns) transformed into
      HAP at 37 degrees C, 100% RH after being mixed with 25 mM phosphoric acid. X-ray
      diffraction suggested that the cement containing fine particles of DCPD and TECP
      completely transformed to HAP, but that mixtures containing larger particles did
      not. Because particle size of both DCPD and TECP affected the compressive
      strength of the cement, the crystal growth of HAP during cement formation
      depended on the specific surface area (Sw) of the raw materials. The crystallite
      size of transformed HAP was estimated based on X-ray diffraction peaks at 25.8
      and 32.8 degrees attributable to the 002 and 300 planes. The crystalline size
      attributable to the 300 plane decreased with increasing Sw, but that attributable
      to the 002 plane showed no significant relationship. The compressive strength of
      the cement after hardening increased with an increase of its Sw. This suggested
      that the harder calcium phosphate cement was (derived) from the smaller particle
      size of the raw materials.

PMID- 7713957
TI  - Surface field of forces and protein adsorption behavior of
      poly(hydroxyethylmethacrylate) films deposited from plasma.
AB  - Polymeric films were deposited from hydroxyethylmethacrylate (HEMA) plasma on non
      woven poly(butyleneterephtalate) (PBT) filter materials. To test the effect of
      deposition conditions on surface properties, film were deposited using a constant
      monomer flow rate and a discharge power ranging from 40-100 W. Surface
      composition and surface energetics were evaluated by Electron Spectroscopy for
      Chemical Analysis (ESCA) and contact angle measurement, respectively. Albumin
      (Alb) and fibrinogen (Fg) adsorption from single protein solutions to the plasma
      coated filters was measured. Results illustrate the marked effects of the
      deposition condition on the surface composition, the surface field of forces, and
      the protein adsorption behavior. The latter is modeled by the application of the
      Good-van Oss-Chaudhury theory of Lewis acid-base contribution to interfacial
      energetics. Materials endowed with widely different properties are obtained from
      the same monomer and different deposition conditions, a result that must be taken
      into account both in the production step, to assure constant quality, and in the
      development of specifically tailored materials.

PMID- 7713956
TI  - Drug release from a novel self-setting bioactive glass bone cement containing
      cephalexin and its physicochemical properties.
AB  - A novel device containing cephalexin as a model drug using a self-setting
      bioactive cement based on CaO-SiO2-P2O5 glass was investigated. The device
      consisted of 95 wt/wt% glass powders and 5 wt/wt% cephalexin powder hardened
      within 5 min after mixing with a phosphate buffer. After setting, in vitro drug
      release from homogeneous or heterogeneous drug-loaded cement pellets in a
      simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for over 4
      weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite with
      high bioactivity in hard bone tissue and reduced in volume by about 5% during
      dissolution testing in SBF. Consequently, 30% of the loaded drug was squeezed
      from the cement system at the initial stage of the drug release, and the
      remainder released more slowly. Because the heterogeneous system consisting of
      the cement and drug-loaded pellet avoided the drug-squeezing effect, it showed a
      longer drug release term than the homogeneous drug-loaded cement. The
      heterogeneous system using the hardened cement after soaking in SBF at 37 degrees
      C for 10 days showed very slow drug release at the initial stage because it
      completely avoided the drug-squeezing effect, and the release was a zero-order
      pattern.

PMID- 7713959
TI  - Kinetic study of release of silicon compounds from polysiloxane tissue expanders.
AB  - The release behavior of typical commercial tissue expanders has been examined by
      carrying out two kinds of experiments: 1) Determination of chemical nature and
      its modification after in vivo use by X-ray photoelectron spectroscopy for
      chemical analysis. This study has been paralleled by scanning electron microscopy
      with associated energy dispersive X-ray analysis of surface, as well as by
      silicon compounds analysis of tissues around implants. 2) Kinetic examination of
      silicon compounds released by the biomaterial in physiologic solution at 36 +/-
      0.3 degrees C. Results of these investigations have shown independently that the
      starting material was not a filler-free, pure polymer, but a composite,
      reinforced elastomer, with the reinforcing agent most seemingly represented by
      silicon dioxide. Release of latter, with a relatively fast kinetics, is
      compatible with data of the simulating laboratory runs in the physiologic
      solution. All these facts seem to rule out any hypothesis of a prevailing
      siloxane oligomer migration. The correlation of kinetic and physicochemical tests
      with the in vivo behavior is discussed.

PMID- 7713960
TI  - Formation and characterization of anodic titanium oxide films containing Ca and
      P.
AB  - Commercially pure titanium was anodized in an electrolytic solution that was
      dissolved calcium and phosphorus compounds in water, and an AOFCP (anodic
      titanium oxide film containing Ca and P) was formed. It was found that sodium
      beta-glycerophosphate (beta-GP) and calcium acetate (CA) were suitable for the
      electrolytes to form the AOFCP having an equivalent Ca/P ratio to hydroxyapatite
      (HA). The AOFCP was characterized by scanning electron microscopy (SEM), an
      energy-dispersive X-ray microanalysis (EDX), and X-ray diffraction (XRD).
      Numerous micropores and microprojections were observed on the AOFCP by SEM. The
      composition of the AOFCP, which was measured by EDX, changed according to beta-GP
      and CA concentration, and the electrolytic voltage. Ca and P in the AOFCP seem to
      be incorporated into the TiO2 matrix from CA and beta-GP in the electrolyte
      during the anodic oxidation. Despite the existence of Ca and P in the AOFCP, no
      calcium phosphate peak was detected by XRD, and the AOFCP consisted of anatase
      and only a little rutile. The AOFCP, whose contents of Ca and P were low, had a
      high adhesive strength after soaking in a simulated body fluid for 300 days. When
      the AOFCP having an equivalent Ca/P ratio to HA was hydrothermally heated at 300
      degrees C, HA crystals were precipitated on the AOFCP and completely covered the
      surface.

PMID- 7713958
TI  - Zeta potential of bone from particle electrophoresis: solution composition and
      kinetic effects.
AB  - The morphology of bone may be influenced by many factors, including
      electromechanical ones such as electric potentials, electric fields, or zeta
      potentials. Stress-generated potential studies in bone and particle
      electrophoresis studies using calcium-deficient hydroxyapatite have shown that
      the zeta potential depends on the composition of the steeping fluid and steeping
      time. To better quantify and understand these in situ potential changes in bovine
      cortical bone, the effects of alterations in calcium, phosphate, and fluoride
      concentrations in Neuman's Fluid (NF), which simulates in vivo bone extracellular
      fluid, were investigated using particle electrophoresis. The zeta potential
      increased in magnitude with increased calcium concentration in NF in as little as
      17 min. Increasing phosphate concentration in NF also increased the zeta
      potential magnitude. These results provide support for a structural model of the
      bone matrix surface-bone fluid interface, which incorporates the bone surface
      proper (composed of collagen, mineral, and boundary regions), stationary layer
      (in which ions, ionic complexes, and proteins may be adsorbed), and bone
      extracellular fluid. These results, coupled with those of previous studies,
      indicate that the protein phase probably has an important role in the
      determination of the physiologic zeta potential; the role of the mineral phase
      may also be important.

PMID- 7713961
TI  - Crystal structure of the surface oxide layer on titanium and its changes arising
      from immersion.
AB  - The passivating surface oxide on titanium is one of the elements considered in
      the explanation of the favorable biologic response of this metal in implant
      applications. In the present study, transmission electron microscopy was used to
      identify the crystal structure and morphology of the oxide film on commercially
      pure titanium specimens before and after immersion in simulated physiologic
      fluids. The results show that the oxide layer is composed mainly of anatase and
      rutile, both of which are tetragonal in structure. Although the simulated
      physiologic fluids did not induce an observable change in the crystal structure
      for the immersion times investigated, the results indicate an immersion-induced
      change in microstructure from a fine-grained to a coarser-grained structure. The
      grain growth observed could be attributed to the growth of the native oxide
      crystals; however, it most likely results from the formation of a new oxide
      layer. The results also support oxide thickening as one of the processes
      associated with passive dissolution of titanium.

PMID- 7713962
TI  - Variation in contact guidance by human cells on a microstructured surface.
AB  - Contact guidance induced by the surface topography of the underlying substratum
      influences the interaction of tissue cells with implanted material. It was the
      aim of this study to compare the reaction of different human cells on the same
      surface microtexture. After staining with fluoresceinediacetate, the orientation
      of human fibroblasts, gingival keratinocytes, neutrophils, monocytes, and
      macrophages on a regular surface microstructure of 1 microns pitch and 1 microns
      depth was analyzed by fluorescence microscopy. Contact guidance could not be
      observed in the experiments with keratinocytes and neutrophils, but 100% of the
      fibroblasts and approximately 20% of the monocytes and macrophages reacted with
      alignment. After 2 h some of the macrophages extended long dendritic cellular
      processes parallel to the long axis of the microstructures.

PMID- 7713963
TI  - Initial bone matrix formation at the hydroxyapatite interface in vivo.
AB  - Dense, sintered, slip-cast hydroxyapatite rods were implanted transfemorally in
      young adult rats. The femora were excised after 2 and 4 weeks and, following
      fixation, either embedded in methyl methacrylate for light microscopy,
      decalcified and prepared for transmission electron microscopy, or freeze
      fractured in liquid nitrogen for scanning electron microscopic analysis. The
      latter was performed on the two tissue fragments that remained after freeze
      fracturing, from which the first contained the implants and the second comprised
      tissue that had been immediately adjacent to the hydroxyapatite rods.
      Undecalcified light microscopic sections revealed extensive bone tissue formation
      around and in contact with the hydroxyapatite rods. The initial bone matrix
      apposed to the implant surface, as demonstrated with scanning electron
      microscopy, was either composed of globular deposits or an organized network of
      collagen fibers. The deposits, which ranged in size from 0.1-1.1 microns, fused
      to form a cement-like matrix to which collagen fibers were attached. Degradation
      of the hydroxyapatite surface resulted in the presence of unidirectionally
      aligned crystallites, with which the newly formed bone matrix was closely
      associated. Ultrastructural analysis of the bone-hydroxyapatite interface with
      transmission electron microscopy revealed a 50-600-nm-wide collagen-free granular
      zone, comprising one or more 40-100-nm-thick electron-dense layer(s). These
      structural arrangements most probably partially represent the globular deposits
      and proteinaceous material adsorbed onto and partially in the degrading
      hydroxyapatite surface. Although the latter change in surface topography may have
      enhanced bonding of the cement-like matrix to the hydroxyapatite, the cause for
      this change in topography and the type of bond formed are, at present, unknown.

PMID- 7713965
TI  - The role of the orthopaedic surgeon in United Nations Peacekeeping Operations.

PMID- 7713964
TI  - Nanoapatite and organoapatite implants in bone: histology and ultrastructure of
      the interface.
AB  - This article reports on the reaction of bone to a new family of nanocrystalline
      hydroxyapatite biomaterials with crystal sizes similar to those of human bone.
      Pure nanoapatite cylinders and organoapatite cylinders containing a synthetic
      nanopeptide were analyzed 28 days after implantation into the spongy bone of
      Chinchilla rabbits. The experimental techniques used for analysis were light
      microscopy, scanning electron microscopy, and transmission electron microscopy.
      Both implant types were well incorporated, and interface events were found to be
      similar to those observed on human bone surfaces with regard to resorption by
      osteoclast-like cells and bone formation by osteoblasts. Different types of giant
      cells were observed resorbing the outermost surfaces of implants. There seemed to
      be both dissolution of the implant and particulate biodegradation leading to less
      dense implant regions near the interface, whereas the bulk of the implants
      remained denser. Transmission electron micrographs revealed that bone bonding
      occurred with and without an afibrillar intervening layer. Given the biologic
      reaction observed, these implant materials should be suitable for bone
      replacement and the organoapatite form could be useful for additional functions
      such as the release of drugs and optimized release of antibiotics, growth
      factors, or other substances. The organic component can also be used to control
      physical properties in a bony implantation bed.

PMID- 7713966
TI  - Calcaneal lengthening for valgus deformity of the hindfoot. Results in children
      who had severe, symptomatic flatfoot and skewfoot.
AB  - Thirty-one severe, symptomatic valgus deformities of the hindfoot in twenty
      children who had flatfoot (twenty-five feet) or skewfoot (six feet) were
      corrected with a modification of the calcaneal lengthening osteotomy described by
      Evans. Despite prolonged non-operative treatment, all patients had pain, a
      callus, ulceration, or a combination of these signs and symptoms under the head
      of the plantar flexed talus; they could not tolerate a brace, and shoe wear was
      excessive. Twenty-six of the deformities were secondary to an underlying
      neuromuscular disorder. The calcaneal lengthening was combined with an opening
      wedge osteotomy of the medial cuneiform to correct the deformities of both the
      hindfoot and the forefoot in the patients who had a skewfoot. Other concurrent
      osseous and soft-tissue procedures were frequently performed in the flatfeet and
      skewfeet to correct adjacent deformities or to balance the muscle forces.
      Allograft bone was used in twenty-four feet and autogenous bone, in seven. The
      patients ranged in age from four years and seven months to sixteen years at the
      time of the operation. The duration of follow-up ranged from two years to three
      years and seven months after the operation. Satisfactory clinical and
      radiographic correction of all components of the deformity of the hindfoot was
      achieved in all but the two most severely deformed feet. These two feet had
      sufficient correction to eliminate the symptoms despite a small persistent callus
      under the head of the talus. The pain and callus were eliminated in all of the
      other feet, the patients were able to tolerate a brace, and shoe wear was
      improved. Subtalar motion was preserved in all feet except for the four that had
      had a limited joint arthrodesis performed previously or simultaneously for pre
      existing degenerative osteoarthrosis. Calcaneal lengthening is effective for the
      correction of severe, intractably symptomatic valgus deformities of the hindfoot
      in children. My patients had resolution of the signs and symptoms associated with
      the deformity while avoiding the need for an arthrodesis and the many short and
      long-term complications associated with it.

PMID- 7713967
TI  - Results of operative treatment of idiopathic scoliosis in adults.
AB  - We compared the results in eighty-one patients (average age, fifty-six years;
      range, forty-three to eighty-three years) who had had operative treatment of
      idiopathic scoliosis with those in thirty patients (average age, fifty-eight
      years; range, forty-five to seventy years) who had declined operative treatment.
      Seventy-six individuals (average age, forty-eight years; range, thirty-five to
      seventy-four years) who did not have scoliosis served as a control group. The
      average duration of follow-up was five years (range, two to seventeen years). The
      population base consisted of 454 patients who were seen between 1970 and 1985.
      The treated patients were drawn from a group of 160 patients for whom an
      operation had been recommended; 110 patients agreed to the operation and fifty
      refused. The remaining 294 patients had curves of insufficient severity to
      warrant concern about progression, had symptoms unrelated to the scoliosis, or
      had curves that did not necessitate any intervention. The functional status since
      the operation (for the treated patients), since recommendation of the operation
      (for the untreated patients), or within the last ten years (for the control
      group) was evaluated with a comprehensive questionnaire designed to elicit
      details regarding pain, fatigue, and any disability in the performance of twenty
      six activities of daily living. At the most recent follow-up examination, the
      treated patients reported a significantly greater decrease in pain and fatigue
      and significantly more improvement in self-image and in the ability to perform
      physical, functional, and positional tasks than did the untreated patients (p =
      0.0001).

PMID- 7713968
TI  - Delayed infections following posterior spinal instrumentation for the treatment
      of idiopathic scoliosis.
AB  - Ten patients who had been managed with posterior spinal arthrodesis and Texas
      Scottish Rite Hospital instrumentation because of idiopathic scoliosis had a
      delayed deep wound infection at an average of twenty-five months after the
      operation. The signs of infection included spontaneous drainage in eight patients
      and fluctuance in two patients. In addition, six patients--including five of the
      eight who had drainage--had mild pain in the back. The average erythrocyte
      sedimentation rate was thirty-nine millimeters per hour (range, nineteen to
      eighty-one millimeters per hour). The instrumentation was removed from all of the
      patients. In two patients, a pseudarthrosis that had not been noted on
      preoperative radiographs was noted intraoperatively; in both patients, the
      pseudarthrosis occurred at a level at which two hooks had been placed in one
      intervertebral space. Primary closure was performed in seven patients, and
      delayed primary closure was performed on the third postoperative day in three
      patients. All wounds healed uneventfully. Cultures of specimens taken from deep
      within the wound were positive for Propionibacterium acnes (five patients),
      Staphylococcus epidermidis (two patients), a rare coagulase-negative
      Staphylococcus species (one patient), or Micrococcus varians (one patient). No
      organisms grew on culture of the specimen obtained from the remaining patient.
      Propionibacterium acnes required an extended period of incubation before
      identification. Antibiotics were administered parenterally to all of the patients
      after the removal of the hardware, and this treatment was followed by oral
      administration of antibiotics for nine of the patients. We suspect--but can not
      prove--that several of the delayed infections resulted from intraoperative
      seeding and remained subclinical for an extended period of time.

PMID- 7713969
TI  - Segmental spinal dysgenesis. A disorder different from spinal agenesis.
AB  - We reviewed the clinical and roentgenographic findings, treatment, and results
      for seventeen patients (six male and eleven female) who had segmental spinal
      dysgenesis, a disorder frequently confused with, but distinct from, lumbar and
      lumbosacral agenesis. The average age at the time of presentation to the
      Minnesota Spine Center or the Gillette Children's Hospital was two and a half
      years (range, newborn to twenty-one years), and the average duration of follow-up
      was eight years (range, five months to twenty-two years). At the time of the
      diagnosis, eight patients had neurological deficits: seven had a neurogenic
      bladder and four had weakness of the lower extremities. An average of 2.6
      procedures (range, one to five procedures) was needed to obtain a solid fusion.
      Decompression of the stenotic canal was performed in ten patients, and it was
      followed by an improvement in neurological function in two of them. A solid
      fusion of the spine, arrest of the progressive kyphosis, and stabilization of
      neurological function were obtained in all patients. We recommend early anterior
      and posterior arthrodesis in patients who have segmental spinal dysgenesis, as
      the progressive kyphosis that inevitably develops often results in neurological
      deficits.

PMID- 7713970
TI  - Divergent single-column fractures of the distal part of the humerus.
AB  - We report an unusual intra-articular fracture of the distal part of the humerus
      that was seen in five patients, including one who had the fracture bilaterally.
      The fractures were characterized by three features. First, the fractures were
      initiated in the trochlear groove as a result of a direct impact on the
      olecranon, which divided the trochlea and then split the two columns of the
      humerus divergently. Second, the fractures occurred exclusively in adolescents
      and young adults (average age, fifteen years old; range, thirteen to twenty years
      old). Third, all of the fractures were seen in patients who had a large fossa or
      septal aperture between the coronoid and olecranon fossae. Four of the fractures
      involved the right side and two, the left. There were three fractures of the
      lateral column and three of the medial column. Because the periosteum, the
      capsule, and the ligaments remained intact despite intra-articular displacement
      of the distal part of the humerus, these fractures were also characterized by
      inherent proximal stability. The fractures were treated with closed reduction and
      percutaneous internal fixation to reduce the displacement between the two halves
      of the trochlea. All of the fractures united. Four patients (five elbows)
      regained full motion by eight months; one patient was lost to follow-up. Current
      classification systems that describe single-column fractures of the distal part
      of the humerus should be modified to include this unusual fracture pattern.

PMID- 7713971
TI  - Regulation of proliferation and osteochondrogenic differentiation of periosteum
      derived cells by transforming growth factor-beta and basic fibroblast growth
      factor.
AB  - We studied the effects of transforming growth factor-beta and basic fibroblast
      growth factor on the regulation of proliferation and osteochondrogenic
      differentiation of periosteum-derived cells, which have the potential to
      differentiate into bone and hypertrophic cartilage in vitro. Histological
      observation revealed that transforming growth factor-beta stimulated
      chondrogenesis of periosteum-derived cells while basic fibroblast growth factor
      stimulated proliferation of fibroblast-like cells and inhibited osteochondrogenic
      differentiation. Immunohistochemical studies revealed that basic fibroblast
      growth factor inhibited the expression of osteocalcin. Transforming growth factor
      beta enhanced uronic acid content but decreased DNA content, alkaline phosphatase
      activity, and calcium content. In contrast, basic fibroblast growth factor
      enhanced DNA content but decreased alkaline phosphatase activity, calcium
      content, and uronic acid content. In addition, transforming growth factor-beta
      shortened the time-course of gene expression of type-X collagen whereas basic
      fibroblast growth factor inhibited the gene expression. These results indicate
      that transforming growth factor-beta stimulates osteochondrogenic differentiation
      of periosteum-derived cells but inhibits proliferation. They also indicate that
      basic fibroblast growth factor stimulates proliferation of periosteum-derived
      cells but inhibits osteochondrogenic differentiation.

PMID- 7713972
TI  - The effect of articular conformity and the size of the humeral head component on
      laxity and motion after glenohumeral arthroplasty. A study in cadavera.
AB  - We used a cadaveric model to examine the mechanical effects of changes in the
      conformity of the articular surfaces and the size of the humeral head component
      in glenohumeral arthroplasty. The experimental system permitted a manual clinical
      examination of the glenohumeral joint while sensors monitored the humeroscapular
      position and orientation as well as the forces and torques applied by the
      examiner. Four preparations were compared: an anatomical humeroscapular
      preparation and three glenohumeral arthroplasty preparations (one with
      anatomically sized components and a radius of curvature of the glenoid that was
      four millimeters larger than that of the humeral head, one with anatomically
      sized components and a radius of curvature of the glenoid that was equal to that
      of the humeral head, and one with a non-anatomical, large humeral head component
      and a radius of curvature of the glenoid that was equal to that of the humeral
      head). All motions, including flexion, external and internal rotation, and
      maximum elevation, were diminished with use of the non-anatomical, large humeral
      head component. Laxity of the joint on drawer and sulcus tests was not affected
      by the conformity of the articular surfaces but was decreased significantly by
      implantation of the large humeral head component. The kinematics of the
      glenohumeral joint were not markedly altered by reduction of the uniformity
      between the articular surfaces of the prosthetic components. In all preparations,
      obligate displacement of the humeral head associated with a passive range of
      motion occurred at smaller angles with the large humeral head component.

PMID- 7713973
TI  - Treatment of soft-tissue sarcomas of the hand.
AB  - We studied the clinical features, radiographic and pathological findings,
      treatment, and results for twenty-three patients who had been managed for a soft
      tissue sarcoma of the hand between 1982 and 1990. The ages of the patients ranged
      from sixteen to seventy-six years (median age, thirty-one years). The most common
      clinical finding was a small, painless soft-tissue mass. Twenty of the tumors
      were high-grade, and eighteen were less than five centimeters in diameter. The
      most common diagnosis was synovial sarcoma, which was identified in eight
      patients. Leiomyosarcoma, rhabdomyosarcoma, and malignant fibrous histiocytoma
      developed in three patients each; epithelioid sarcoma, in two patients; and
      angiosarcoma, liposarcoma, neuroectodermal tumor, and clear-cell sarcoma, in one
      patient each. Curative wide excision or amputation was attempted in twenty-two
      patients; the margins were positive for tumor cells in eight, and local
      recurrence was seen in nine. Of the twenty-three patients, fourteen had survived,
      without evidence of disease, after a median duration of follow-up of forty-nine
      months, and nine had died of disease. The median rate of survival did not differ
      significantly on the basis of the size or grade of the tumor or the use of
      adjuvant treatment. However, the rate of survival of the patients who had a soft
      tissue sarcoma of the hand that was less than five centimeters in diameter was
      significantly lower (p = 0.0008) than that of 152 patients who had a similar
      tumor at another site in an extremity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713974
TI  - Long-term intravenous therapy with use of peripherally inserted silicone
      elastomer catheters in orthopaedic patients.
AB  - We studied the results of prolonged intravenous therapy with antibiotics through
      a central venous silicone-elastomer catheter that had been peripherally inserted
      in thirty-five orthopaedic patients. The catheters remained in place for an
      average of twenty-nine days (range, five to seventy-four days). The 20-gauge (one
      millimeter-diameter) catheters used in our study were smaller in diameter than
      the triple-lumen catheters or the double-lumen Hickman catheters used in previous
      studies. The catheters in our study were left indwelling for as long as, or for
      longer than, those in other studies. Our patients had no serious complications
      related to the insertion or use of the catheter. However, three (8 per cent) of
      thirty-eight inserted catheters failed mechanically and had to be removed. Two
      additional catheters (5 per cent) were removed because the lumen became plugged.
      One catheter in each of these groups was not replaced, because a catheter was no
      longer necessary. We believe that the problems with the catheters were related to
      the small diameter of the tubing that was used in our series. Use of the small
      diameter catheter reduces the risk of cardiac tamponade and other complications
      associated with catheters that have larger diameters, and small-diameter
      catheters can remain indwelling for a long time. The peripheral route of
      insertion eliminates the risk of pneumothorax associated with the subclavian
      route of placement and allows for greater ease of insertion. In addition, the use
      of catheters made of silicone elastomer reduces the risk of thrombosis and
      infection, which are associated with catheters made of polyethylene.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7713976
TI  - Revision of total hip arthroplasty in octogenarians.
AB  - Twenty-seven revision total hip arthroplasties were performed in patients who
      were at least eighty years old. The average duration of follow-up was five years.
      There were no perioperative deaths, and only 11 per cent (three) of the patients
      had a major complication; all of the complications resolved. The only re-revision
      was the placement of an extended lip-liner for the treatment of recurrent
      dislocation. Of the twenty-five patients who were alive at the time of the most
      recent follow-up or who had been survived by a family member who could be
      interviewed, twenty-one (84 per cent) said that the operation had improved
      function, twenty-three (92 per cent) had less pain, and twenty-two (88 per cent)
      were satisfied with the result.

PMID- 7713975
TI  - Percutaneous lumbar discectomy. Preoperative and postoperative magnetic resonance
      imaging.
AB  - We evaluated magnetic resonance imaging studies of thirty patients before and
      after a contained herniation of a lumbar disc was treated with a percutaneous
      lumbar discectomy. The imaging studies were evaluated to determine whether the
      preoperative appearance of the herniated disc was predictive of the outcome of
      percutaneous discectomy and also to determine a possible mechanism of action of
      the procedure in the relief of symptoms. The index operation was successful in
      seventeen (57 per cent) of the thirty patients. The preoperative imaging studies
      showed no differences in the appearance of the discs that went on to have a
      successful result and those that went on to have an unsuccessful result. Imaging
      studies made four to six weeks after the operation showed no measurable changes
      in the morphology of the disc. Imaging studies made a mean of fourteen months
      after the operation showed no changes in the morphology of the disc in twenty
      four (80 per cent) of the patients, irrespective of the clinical outcome. Only
      three of the seventeen patients who had a successful result had a reduction of
      more than two millimeters in the size of the herniated segment, and two of the
      thirteen patients who had an unsuccessful result had an increase of more than one
      millimeter in the size of the herniated segment. We found that preoperative
      imaging studies cannot predict the clinical outcome of percutaneous lumbar
      discectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713977
TI  - Single-dose irradiation for the prevention of heterotopic ossification after
      total hip arthroplasty. A comparison of doses of five hundred and fifty and seven
      hundred centigray.
AB  - One hundred and seven hips (ninety-four patients) that had risk factors
      associated with the development of heterotopic ossification after total hip
      arthroplasty were treated with a single dose of radiation after the operation in
      an attempt to prevent the formation of heterotopic bone. A study was conducted to
      compare the efficacy of a single dose of 550 centigray (nineteen hips) with that
      of a single dose of 700 centigray (eighty-eight hips). Heterotopic ossification
      developed in twelve (63 per cent) of the nineteen hips that were treated with 550
      centigray; grades 1, 2, and 3, according to the classification of Brooker et al.,
      developed in four hips each. Two of the patients who received 550 centigray were
      symptomatic. Heterotopic ossification developed in nine (10 per cent) of the
      eighty-eight hips that were treated with 700 centigray; the lesion was grade 1 in
      six, grade 2 in one, and grade 3 in two. None of the patients who received 700
      centigray were symptomatic. We concluded that single-dose irradiation consisting
      of 550 centigray is inadequate for the prevention of heterotopic ossification in
      high-risk patients after total hip arthroplasty. We recommend a dose of 700
      centigray as effective prophylaxis for these patients.

PMID- 7713978
TI  - Osteonecrosis of the medial part of the tibial plateau.
AB  - Fifteen elderly patients (sixteen knees) were seen because of acute pain in the
      knee and tenderness to palpation over the medial aspect of the tibial plateau.
      Initially, plain roentgenograms showed a radiolucent area at the site of the
      tenderness in only nine of the sixteen knees. However, radionuclide bone scans
      showed focal increased uptake at the site of the tenderness in four of the seven
      remaining knees, and magnetic resonance images showed discrete areas of low
      signal intensity at the same site in the other three knees. Plain roentgenograms
      eventually showed the typical lesion in all knees. Progression of the symptoms
      led to a total knee arthroplasty in nine knees and to a unicompartmental
      replacement in three; a satisfactory result was obtained in all twelve knees. An
      operation was recommended for two other knees, but it was refused by the
      patients. The symptoms resolved spontaneously in the remaining two knees. A
      degenerative tear in the medial meniscus, which is a common finding in this age
      group, was noted at the time of a later operation in the three knees that had not
      had a radiolucent area on the initial plain roentgenograms but that had had an
      area of low signal intensity on the magnetic resonance images. If osteonecrosis
      of the tibial plateau is not considered as a potential cause of pain in the knee,
      symptoms may be attributed to a tear in the meniscus and an unnecessary and
      unproductive arthroscopy may be performed.

PMID- 7713979
TI  - Characteristics of the articular cartilage formed after intertrochanteric
      osteotomy. A case report.

PMID- 7713981
TI  - Distinguishing transient osteoporosis from avascular necrosis of the hip.

PMID- 7713982
TI  - Early failure of short-segment pedicle instrumentation for thoracolumbar
      fractures. A preliminary report.

PMID- 7713980
TI  - Spectrum of injury and treatment options for isolated dislocation of the
      scaphoid. A report of three cases.

PMID- 7713983
TI  - Effects of sectioning of the posterior cruciate ligament and the posterolateral
      complex on the articular contact pressures within the knee.

PMID- 7713984
TI  - Current concepts review. The diagnosis and orthopaedic treatment of inherited
      muscular diseases of childhood.

PMID- 7713987
TI  - "Atypical" multidrug resistance in human ovarian cancer cell line A2780 selected
      for resistance to doxorubicin (A2780 DX3).
AB  - Human ovarian cancer cells A2780, selected for resistance to doxorubicin (A2780
      DX3), are cross-resistant to various other topoisomerase-II-targeted drugs but
      not to vinblastine. The parental cell line was very sensitive to doxorubicin-,
      mitoxantrone- or etoposide(VP16)-induced DNA single-strand breaks, under
      deproteinizing conditions. In contrast, little or no DNA strand breakage was seen
      in resistant A2780-DX3 cells, even at very high concentrations, indicating a good
      correlation, with cytotoxicity. No significant alterations in cellular drug
      uptake were observed in DX3 cells. Further studies showed that the nuclei
      isolated from resistant cells were also resistant to mitoxantrone- or VP16
      induced single-strand breaks, indicating that nuclear modifications in resistant
      cells are responsible for this resistance. Catalytic activity in crude nuclear
      extracts from wild-type and DX3 cells was almost equal. However, an assay that
      specifically measures generation of 5'-protein-linked breaks in 32P-labeled 3 DNA
      revealed that, DNA cleavage activity in nuclear extract from the DX3 cell line is
      profoundly resistant to a stimulation by VP16. These data indicate that
      stimulation of topoisomerase-II-mediated DNA cleavage is responsible for
      topoisomerase-II-targeted drug-cytotoxicity rather than loss of normal
      topoisomerase catalytic function. These data support the hypothesis that A2780
      DX3 cells display an "atypical" multidrug resistance.

PMID- 7713988
TI  - Antiproliferative activity of liposomal epirubicin on experimental human gliomas
      in vitro and in vivo after intratumoral/interstitial application.
AB  - Liposomal epirubicin was prepared using the controlled detergent dialysis method.
      The entrapment rate was 65.5 +/- 6.4%. The mean particle size was 210 +/- 38 nm.
      In vitro, a concentration-dependent antiproliferative activity of free epirubicin
      was observed. Liposome-entrapped epirubicin was superior to the free drug; the
      ID50 of the liposomal preparation was about 1.6-fold lower as compared to the
      free drug. Intratumoral/interstitial (i.t./i.s.) application of liposomal
      epirubicin was likewise superior to i.t./i.s. application of the free drug.

PMID- 7713986
TI  - Growth inhibition of DMBA-induced rat mammary carcinomas by the antiandrogen
      flutamide.
AB  - Antiandrogens have sporadically been reported to exert antitumor activities in
      both pre- and post-menopausal breast cancer. To explore the possibility of using
      the pure antiandrogen flutamide (FLU) in breast cancer therapy, rats bearing DMBA
      induced mammary tumors were treated with FLU, dihydrotestosterone (DHT), or FLU
      plus DHT. FLU was administered orally, at doses comparable to those used in the
      treatment of prostate cancer patients. FLU-treated animals had a significantly
      smaller average tumor area than controls from day 11 up to the end of the
      experiment (day 20). A similar reduction of tumor growth was observed in rats
      given DHT and in those treated with DHT plus FLU. Plasma levels of LH, FSH, P, 17
      OH P, E2 and DHEA measured at the end of experiment did not differ between
      treated animals and controls. Results demonstrate that the antiandrogen FLU and
      the full androgen DHT exert similar inhibitory effects on the growth of
      dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. Moreover, data show
      that plasma steroids levels are unaffected by FLU treatment. This finding rules
      out any antitumor effect dependent on the reduction of adrenal and gonadal
      steroidosynthesis, and makes it appear more likely that androgen receptors are
      involved in the antiproliferative effect of FLU.

PMID- 7713985
TI  - Alterations in receptor-mediated kinases and phosphatases during carcinogenesis.
AB  - Increased phosphorylation in cancers can stimulate growth and up-regulate certain
      receptors. To test whether the functional response of phosphatase receptors is up
      regulated during carcinogenesis, we examined the effects of ligands on net
      phosphorylation in isolated membranes derived from hamster cheek-pouch tissues
      undergoing malignant transformation. The buccal mucosa of groups of Syrian golden
      hamsters was exposed thrice weekly to 0.5% dimethylbenzanthracene (DMBA) in
      acetone for 2-12 weeks to produce premalignant and malignant tissues. Homogenates
      of these tissues were then incubated with [32P]ATP in the presence of epidermal
      growth factor (EGF), agonist of somatostatin analogue RC-160, luteinizing-hormone
      releasing hormone (LH-RH) [D-Trp6]LH-RH, or combinations of EGF, RC-160, and [D
      Trp6]LH-RH. Changes compared to controls in phosphorylation in response to
      ligands provided estimates of kinase or phosphatase activity. Phosphorylation
      increased continuously, from the first application of DMBA in a linear fashion,
      and independently of EGF stimulation. RC-160 and [D-Trp6]LH-RH reduced
      phosphorylation in vitro. This response occurred in premalignant (weeks 6-10
      after DMBA application) as well as malignant tissues (week 12 after DMBA
      application), but was not significant in normal tissues. The results show a
      continuous augmentation in phosphatase activity prior to the appearance of
      cancers, but with a delay in expression following the primary event of increased
      kinase activity. Significantly less phosphorylation of substrates was induced by
      both RC-160 and [D-Trp6]LH-RH after in vitro activation by EGF than in the
      absence of EGF. This suggests that EGF activates latent systems of hormonal
      receptors. Collectively, these results support the hypothesis that the
      enhancement of the hormonally stimulated phosphatase in cancers occurs
      secondarily to the increased kinase activity.

PMID- 7713989
TI  - The effect of a mesogenic and a lentogenic Newcastle disease virus strain on
      Burkitt lymphoma Daudi cells.
AB  - The destructive effect of Newcastle disease virus (NDV) strains on Burkitt
      lymphoma Daudi cells was investigated. Interaction of an active and UV
      inactivated mesogenic strain (Roakin), as well as an active attenuated lentogenic
      strain (B1), grown in the allantoic sac of embryonated eggs, at high
      multiplicity, caused inhibition in cellular DNA synthesis and arrest in cell
      multiplication, eventually killing of the cells. The lentogenic strain cultivated
      in chicken fibroblasts exhibited only a moderate activity. The mechanism of the
      cytolytic effect is presumably linked to the increase in cell membrane
      permeability indicated by the elevation in 51Cr release. Thus it appears that the
      massive adsorption and/or penetration of viral particles, active or UV
      inactivated (or possibly a toxic component that resides in the virion), damages
      the plasma membrane and may be responsible for the killing of the cells.

PMID- 7713991
TI  - Differentiated thyroid carcinoma as a cause of cervical spinal injury.
AB  - Cervical cord compression due to local extension of differentiated thyroid
      carcinoma (DTC) is an extremely rare condition and, to our knowledge, only one
      case has been reported in the literature. Among 256 patients with DTC treated at
      our hospital, we have observed 3 cases of spinal injury due to local extension of
      DTC. A Brown-Sequard syndrome was detected at physical examination in 2 cases. In
      both patients, cervical cord compression precipitated a fatal event. In the
      remaining patient, a radiculopathy C5-C7 was observed. Magnetic resonance imaging
      was very successful in outlining the mass, clearly differentiating the extrinsic
      invasion from a metastasis, and allowing the surgical possibilities to be
      evaluated. Poor cervical uptake of 131I was observed on scans performed in two
      cases, suggesting a certain degree of cell dedifferentiation. We suggest that
      cervical spinal injury due to local extension of DTC may be an underreported
      complication of DTC that seems to condition the patient's outcome. Careful
      neurological examination is warranted in patients with DTC at stages III-IV and
      magnetic resonance imaging must be performed when spinal injury is suspected.

PMID- 7713990
TI  - Rhythm alteration in patients with metastatic breast cancer and poor prognostic
      factors.
AB  - Circulating blood cell counts, serum cortisol, proteins, alkaline phosphatase,
      carcinoembryonic antigen and CA15.3 displayed significant circadian rhythms in a
      group of 13 women with metastatic breast cancer. Statistical significance (P <
      0.05) was assessed with both analysis of variance and cosinor analysis. All
      patients had been previously treated with chemo-and/or radiotherapy and/or
      antiestrogens. All patients had been treatment-free for 1 month prior to the
      study. Each patient had blood drawn every 4 h for 48 h. Circadian rhythms were
      examined as a function of performance status, graded according to the World
      Health Organization, liver involvement and number of metastatic sites. Group
      circadian rhythms in serum cortisol or proteins were abolished in patients with
      liver metastases, and were altered in cases of poor performance status.
      Circulating leukocytes, neutrophils or platelets did not exhibit synchronized
      circadian rhythmicity in patients with poor performance status or liver
      metastases. The number of metastatic organs had a minor influence on circadian
      rhythmicity. These results suggest that rhythm alteration may be associated with
      both poor performance status and liver metastases in patients with advanced
      breast cancer. Such alteration of the normal circadian time structure may favor
      and/or result from cancer spread.

PMID- 7713993
TI  - Commentary and opinion: II. Statistical parametric mapping: ontology and current
      issues.

PMID- 7713994
TI  - Commentary and opinion: III. Some nonontological and functionally unconnected
      views on current issues in the analysis of PET datasets.
AB  - Strother et al. (1995) and Friston (1995) both raise important issues and provide
      useful reviews of various aspects of PET data analysis. Statisticians would not
      assume that any single piece of methodology would answer all questions about a
      type of data in a variety of experimental and observational contexts. The
      fundamental importance of hypothesis-driven inference, based on well designed
      experiments, cannot be overestimated for its ability to progress scientific
      understanding in an orderly manner. However, hypothesis-generating experiments
      are also vital in their own right. In practice, we generally do not have the
      luxury of both types of experiment, and we should note Strother et al.'s comment
      on the importance of extracting as much information as possible from each
      dataset. Friston (1995) also sees formal testing methods and exploratory methods
      such as principal components analysis as complementary. The correct approach
      would therefore seem to be (a) to select methods for formal and exploratory data
      analysis from the rich existing tool kit of statistical procedures, (b) to modify
      these as necessary to deal with special PET problems such as multiplicity, (c) to
      be aware of the assumptions underlying the methods being used and to investigate
      the problems that can arise if these assumptions fail to hold, (d) to appreciate
      the complexity of both PET data and of the potential questions that can be asked
      of it, and (e) to be aware of the limitations of any statistical analysis and the
      need for caution in interpreting conclusions not based on any predefined
      hypothesis.

PMID- 7713992
TI  - Commentary and opinion: I. Principal component analysis, variance partitioning,
      and "functional connectivity".
AB  - We briefly review the need for careful study of "variance partitioning" and
      "optimal model selection" in functional positron emission tomography (PET) data
      analysis, emphasizing the use of principal component analysis (PCA) and the
      importance of data analytic techniques that allow for heterogeneous spatial
      covariance structures. Using an [15O]water dataset, we demonstrate that--even
      after data processing--the intrasubject signal component of primary interest in
      baseline activation studies constitutes a very small fraction of the intersubject
      variance. This small intrasubject variance component is subtly but significantly
      changed by using analysis of covariance instead of scaled subprofile model
      processing before applying PCA. Finally, we argue that the concept of "functional
      connectivity" should be interpreted very generally until the relative roles of
      inter- and intrasubject variability in both disease and normal PET datasets are
      better understood.

PMID- 7713995
TI  - Early endonuclease activation following reversible focal ischemia in the rat
      brain.
AB  - The structural changes that occur in chromatin DNA after ischemic brain injury
      are poorly understood. The presence of oligonucleosome fragments that are
      recognized as the characteristic DNA ladder has been demonstrated in global and
      focal ischemia, associated or not with random DNA fragmentation. Using pulsed
      field gel electrophoresis, which improves DNA separation, we have now detected
      initial stages of DNA fragmentation that occur already 6 h after reversible focal
      cerebral ischemia in rats. This result confirms that internucleosomal DNA
      fragmentation precedes random DNA fragmentation in vulnerable striatal and
      cortical neurons following reversible focal cerebral ischemia.

PMID- 7713996
TI  - Temporal profile of in situ DNA fragmentation after transient middle cerebral
      artery occlusion in the rat.
AB  - We measured the temporal profile and anatomic distribution of cells exhibiting
      DNA fragmentation at various durations of reperfusion after middle cerebral
      artery (MCA) occlusion in the rat. Focal cerebral ischemia was induced in male
      Wistar rats (n = 62) using an intraluminal monofilament blockade of the MCA.
      After 2 h of MCA occlusion, the animals were killed at different durations of
      reperfusion (0.5, 3, 6, 9, and 12 h and 1, 2, 4, 7, 14, 21, and 28 days, n = 4
      per time point). Sham-operated rats (n = 4) and normal rats not subjected to any
      surgical procedure (n = 4) were used as controls. Coronal brain sections (5
      microns) were analyzed, using an in situ ApopTag kit, hematoxylin and eosin, and
      immunohistochemical double-staining methods. Six rats subjected to 2 h of MCA
      occlusion were killed at 24 h for measurement of DNA fragmentation by gel
      electrophoresis. Our data indicate that within a coronal section, DNA
      fragmentation was present in zero to three cells in each hemisphere of normal and
      sham-operated rats as well as in the contralateral hemisphere of ischemic rats.
      The number of cells exhibiting DNA fragmentation increased as early as 0.5 h (8
      +/- 6), peaked at 24-48 h (213 +/- 59), and persisted for 4 weeks (10 +/- 2)
      after onset of reperfusion (p < 0.01). Groups of cells exhibiting DNA
      fragmentation (> 95% neurons) were located primarily in the inner boundary zone
      of the infarct. With use of gel electrophoresis, purified DNA obtained from the
      ischemic tissue exhibited the characteristic nucleosome ladder pattern associated
      with apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713997
TI  - Local cerebral glucose utilization and cytoskeletal proteolysis as indices of
      evolving focal ischemic injury in core and penumbra.
AB  - To ascertain the tempo of progression to irreversible injury in focal ischemia,
      we subjected halothane-anesthetized Sprague-Dawley rats to photochemically
      induced distal middle cerebral artery occlusion (dMCAO) combined with permanent
      ipsilateral and 1 h contralateral common carotid artery occlusions. Head
      temperature was maintained at 36 degrees C. At times centered at either 1.5 or 3
      h post-dMCAO, the rate of local glucose metabolism (lCMRgl) was measured by 2
      deoxyglucose autoradiography, and cytoskeletal proteolysis was assessed
      regionally by an immunoblotting procedure to detect spectrin breakdown products.
      At 1.5 h (n = 5), the cortical ischemic core was already severely hypometabolic
      (lCMRgl 15.5 +/- 10.8 mumol 100 g-1 min-1, mean +/- SD), whereas the cortical
      penumbral zone was hypermetabolic (69.0 +/- 9.7). (The lumped constant was
      verified to be unchanged by methylglucose studies). Neutral red pH studies at
      this time point showed that both the core and penumbral zones were equally
      acidotic. By 3 h post-dMCAO (n = 6), lCMRgl in the penumbral zone had fallen to
      low levels (15.4 +/- 2.2 mumol 100 g-1 min-1) equal to those of the ischemic core
      (16.7 +/- 4.5). Correspondingly, spectrin breakdown in the ischemic core was
      advanced at both 2 and 3.5 h post-dMCAO (36 +/- 18% and 33 +/- 18% of total
      spectrin, respectively), whereas in the penumbral zone spectrin breakdown was
      less extensive and more highly variable at both times (22 +/- 23% and 29 +/-
      16%). We conclude that irreversible deterioration of the ischemic core, as
      evidenced by the onset of local cytoskeletal proteolysis, begins within 2 h of
      middle cerebral artery occlusion. In the ischemic penumbra, the transition from
      glucose hyper- to hypometabolism occurs by 3.5 h and is associated with a milder
      and more variable degree of spectrin breakdown.

PMID- 7713998
TI  - Astrocytic swelling due to hypotonic or high K+ medium causes inhibition of
      glutamate and aspartate uptake and increases their release.
AB  - Astrocytic swelling occurs readily in ischemia and traumatic brain injury (TBI)
      as part of the cytotoxic or cellular edema response. Ischemia is known to produce
      large extracellular increases in both [K+] and excitatory amino acids (EAA) in
      vivo, and astrocytic swelling in vitro leads to marked release of EAA. In this
      study we compared the effect of swelling due to hypotonic media and high K+
      medium on the uptake and release of EAA by rat primary astrocyte cultures in
      vitro. In both cases, there was a significant inhibition of uptake of [3H]L
      glutamate and [3H]D-aspartate, and increased release of preloaded [3H]D
      aspartate. The kinetics of the increased efflux was very different in response to
      hypotonic or high K+ media. In hypotonic medium there was a rapid initial release
      followed by a decline in the rate of release over time. This release was
      independent of whether Na+ was present. Upon exposure to high K+ medium there was
      a slow progressive increase in release of [3H]D-aspartate, which never showed any
      subsequent decline until the media was returned to normal [K+]. In high K+ media
      there was also an initial transient increase in [3H]D-aspartate release, which we
      attribute to reversal of the amino acid uptake system. The increased release due
      to hypotonic medium was not affected by a drop in temperature from 37 to 26
      degrees C, while the increased release due to high K+ medium was completely
      inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7713999
TI  - Acidosis causes failure of astrocyte glutamate uptake during hypoxia.
AB  - Failure of glutamate uptake during ischemia can lead to neurotoxic accumulations
      of glutamate in brain extracellular space. Hypoxia and acidosis are metabolic
      consequences of ischemia that may individually or in combination impair glutamate
      uptake. We used primary rat astrocyte cultures to study the effects of acidosis,
      chemical hypoxia, and the combination of acidosis plus chemical hypoxia on
      glutamate uptake. Chemical hypoxia alone reduced uptake by 35-45%. Reduction in
      pH from 7.4 to 5.8 also caused a significant but incomplete inhibition of
      glutamate uptake, and this effect was more pronounced in medium buffered with
      CO2/bicarbonate. However, the combination of chemical hypoxia plus acidosis
      reduced glutamate uptake to below 10% of controls. Astrocyte ATP levels, like
      glutamate uptake, were significantly reduced by chemical hypoxia and further
      reduced by the combination of hypoxia plus acidosis. Acidosis under normoxic
      conditions had no significant effect on astrocyte ATP levels. These results
      suggest two mechanisms by which acidosis may contribute to failure of astrocyte
      glutamate uptake during ischemia: Acidosis may act in concert with hypoxia to
      cause ATP depletion, and acidosis may also have direct effects on glutamate
      transporters unrelated to effects on cellular ATP levels. pH effects on glutamate
      uptake may be an important factor affecting neuronal survival during incomplete
      ischemia.

PMID- 7714000
TI  - Protective effects of antiarrhythmic agents against anoxic injury in CNS white
      matter.
AB  - Irreversible anoxic injury is dependent on extracellular Ca2+ in mammalian CNS
      white matter, with a large portion of the pathologic Ca2+ influx occurring
      through reverse Na(+)-Ca2+ exchange, stimulated by increased intracellular [Na+].
      This Na+ leak likely occurs via incompletely inactivated voltage-gated Na+
      channels. This study reports that clinically used antiarrhythmic compounds,
      likely by virtue of their Na+ channel-blocking properties, significantly protect
      CNS white matter from anoxia at concentrations that cause little suppression of
      the preanoxic response. Rat optic nerves were pretreated with various agents for
      60 min, then subjected to 60 min of anoxia in vitro. Functional recovery was
      measured electrophysiologically as the area under the compound action potential
      (CAP). Without drug, the CAP areas recovered to a mean of 32 +/- 12% of control
      after 1 h of reoxygenation. Recoveries using prajmaline 10 microM were 82 +/- 15%
      (p < 0.0001), and using tocainide 1 mM, 78 +/- 8% (p < 0.0001), with little
      suppression (< or = 10%) of the preanoxic response. Ajmaline (10-100 microM),
      disopyramide (10-300 microM) and bupivacaine (10-100 microM) were somewhat less
      effective, whereas verapamil produced 52 +/- 11% recovery before reduction of the
      preanoxic CAP was observed at 30 microM. Procainamide (100-300 microM) was
      ineffective. These results suggest that Na+ channel blockers, including commonly
      used antiarrhythmic agents, may be effective in protecting central white matter,
      which is a target for anoxic/ischemic injury in diseases such as stroke and
      spinal cord injury.

PMID- 7714001
TI  - Protection against CNS ischemia by temporary interruption of function-related
      processes of neurons.
AB  - Previous studies have shown that most of the energy consumption of CNS tissue is
      used for processes that subserve signaling functions of the cells. Since these
      function-related processes are probably not essential to cell viability, blocking
      them reversibly with a combination of pharmacologic agents should protect cells
      from a reduction in energy metabolism. Preliminary experiments to test this
      hypothesis were performed on isolated rabbit retinas. They were maintained in a
      newly devised chamber that permitted continuous monitoring of
      electrophysiological function for > or = 8 h. Ischemia was simulated by a 6-fold
      reduction in both O2 and glucose. This caused a rapid (t1/2 75 s) and complete
      loss of the light-evoked response in the optic nerve. Untreated retinas showed
      full recovery after 1/2 h of deprivation, but only 50% recovery after 1 h and
      little or no recovery after 2 or 3 h. Retinas exposed during 3 h of deprivation
      to a combination of six agents that abolished electrophysiologic function and
      reduced glucose utilization [tetrodotoxin (TTX), 2-amino-4-phosphonobutyric acid
      (APB), 2-amino-5-phosphonovaleric acid (APV), amiloride, Mg2+, and Li+] showed
      full recovery. We conclude that reducing energy requirements by blocking
      functional processes can prevent ischemic damage.

PMID- 7714002
TI  - Neuroprotection by peptide growth factors against anoxia and nitric oxide
      toxicity requires modulation of protein kinase C.
AB  - Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) are
      neuroprotective during anoxia and nitric oxide (NO) toxicity. Signal transduction
      systems that modulate protein kinase C (PKC) also can modulate the toxic effects
      of anoxia and NO. We therefore examined whether PKC was involved in the
      protective effects of bFGF and EGF during anoxia and NO toxicity. Down-regulation
      or inhibition of PKC activity before anoxia or NO exposure prevented hippocampal
      neuronal degeneration. Yet, this protective effect of inhibition of PKC activity
      was not present with the coadministration of growth factors. Combined inhibition
      of PKC activity and application of bFGF or EGF lessened the protective mechanisms
      of the growth factors. In addition, the protective ability of the growth factors
      was lost during anoxia and NO exposure with the activation of PKC, suggesting
      that at least a minimal degree of PKC activation is necessary for growth factor
      protection. Although modulation of PKC activity may be a necessary prerequisite
      for protection against anoxia and NO toxicity by bFGF and EGF, only inhibition of
      PKC activity, rather than application of the growth factors, was protective
      following exposure to NO. These results suggest that the mechanism of protection
      by bFGF and EGF during anoxia and NO toxicity appears initially to be dependent
      on a minimum degree of PKC activation, but that other signal transduction
      pathways independent of PKC also may mediate protection by peptide growth
      factors.

PMID- 7714003
TI  - Effect of cerebral ischemia on calcium/calmodulin-dependent protein kinase II
      activity and phosphorylation.
AB  - The effects of cerebral ischemia on calcium/calmodulin-dependent kinase II (CaM
      kinase II) were investigated using the rat four-vessel occlusion model. In
      agreement with previous results using rat or gerbil models of cerebral ischemia
      or a rabbit model of spinal cord ischemia, this report demonstrates that
      transient forebrain ischemia leads to a reduction in CaM kinase II activity
      within 5 min of occlusion onset. Loss of activity from the cytosol fractions of
      homogenates from the neocortex, striatum, and hippocampus correlated with a
      decrease in the amount of CaM kinase alpha and beta isoforms detected by
      immunoblotting. In contrast, there was an apparent increase in the amount of CaM
      kinase alpha and beta in the particulate fractions. The decrease in the amount of
      CaM kinase isoforms from the cytosol but not the particulate fractions was
      confirmed by autophosphorylation of CaM kinase II after denaturation and
      renaturation in situ of the blotted proteins. These results indicate that
      ischemia causes a rapid inhibition of CaM kinase II activity and a change in the
      partitioning of the enzyme between the cytosol and particulate fractions. CaM
      kinase II is a multifunctional protein kinase, and the loss of activity may play
      a critical role in initiating the changes leading to ischemia-induced cell death.
      To identify a structural basis for the decrease in enzyme activity, tryptic
      peptide maps of CaM kinase II phosphorylated in vitro were compared.
      Phosphopeptide maps of CaM kinase alpha from particulate fractions of control and
      ischemic samples revealed not only reduced incorporation of phosphate into the
      protein but also the absence of a limited number of peptides in the ischemic
      samples. This suggested that certain sites are inaccessible, possibly due to a
      conformational change, a covalent modification of CaM kinase II, or steric
      hindrance by an associated molecule. Verifying one of these possibilities should
      help to elucidate the mechanism of ischemia-induced modulation of CaM kinase II.

PMID- 7714004
TI  - A synaptic vesicle-associated protein (SVP-38) as an early indicator of delayed
      neuronal death.
AB  - Sixteen gerbils were subjected to 5 min of forebrain ischemia. Their brains were
      processed for immunohistochemical staining using monoclonal antibodies against a
      synaptic vesicle-associated protein 38 (SVP-38) and microtubule-associated
      protein 2 (MAP2) after recirculation times of 10 min, and 1, 4, and 7 days. After
      10 min recirculation, SVP-38 immunoreactive dots were observed only in the CA1
      region of the hippocampus. After 1 day recirculation, SVP-38 immunostaining was
      diffuse and weak throughout the hippocampus, despite preservation of MAP2
      immunoreactivity. After 4 and 7 days recirculation, SVP-38 immunoreactivity had
      been restored in the whole hippocampus, despite the complete loss of MAP2
      immunoreactivity due to delayed neuronal death. Our results demonstrate an
      immediate and significant change in the immunoreactivity of a synaptic vesicle
      associated protein at the beginning of the process of delayed neuronal death.
      Thus, changes in the immunoreactivity of synaptic vesicle-associated proteins
      such as SVP-38 appear to be one of the earliest indicators of the onset of
      neuronal death.

PMID- 7714005
TI  - Regional induction of c-fos and heat shock protein-72 mRNA following fluid
      percussion brain injury in the rat.
AB  - To evaluate the cellular response to traumatic brain injury, the expression of
      mRNA for c-fos and the 72-kDa heat shock protein (hsp72) was determined using in
      situ hybridization following lateral fluid-percussion injury (2.2-2.4 atm) in rat
      brain. At 2 h after injury, induction of c-fos mRNA was observed throughout the
      cortex ipsilateral to the site of injury, while increased expression of hsp72
      mRNA was restricted to regions of the cortex surrounding the contusion area. An
      increase in c-fos mRNA, but not hsp72 mRNA, was observed bilaterally in the CA3
      subfield of the hippocampus and the granule cells of the dentate gyrus and in the
      thalamus ipsilateral to the impact site. By 6 h, increased expression of c-fos
      mRNA was observed only in the corpus callosum on the impact side; hsp72 mRNA
      persisted in the deep cortical layers and upper layers of the subcortical white
      matter below the site of maximal injury. By 24 h, both c-fos and hsp72 mRNA had
      returned to control levels in all regions of the brain. These results demonstrate
      that lateral fluid-percussion brain injury triggers regionally and temporally
      specific expression of c-fos and hsp72 mRNA, which may be suggestive of
      differential neurochemical alterations in neurons and glia following experimental
      brain injury.

PMID- 7714006
TI  - Analysis of time courses of metabolic precursors and products in heterogeneous
      rat brain tissue: limitations of kinetic modeling for predictions of
      intracompartmental concentrations from total tissue activity.
AB  - The efficacy of various kinetic models to predict time courses of total
      radioactivity and levels of precursor and metabolic products was evaluated in
      heterogeneous samples of freeze-blown brain of rats administered
      [14C]deoxyglucose ([14C]DG). Two kinetic models designed for homogeneous tissues,
      i.e., a no-product-loss, three-rate-constant (3K) model and a first-order-product
      loss, four-rate-constant (4K) model, and a third kinetic model designed for
      heterogeneous tissues without product loss [Tissue Heterogeneity (TH) Model] were
      examined. In the 45-min interval following a pulse of [14C]DG, the fit of the TH
      Model to total tissue radioactivity was not statistically significantly better
      than that of the 3K Model, yet the TH Model described the time courses of [14C]DG
      and its metabolites more accurately. The TH- and 4K-Model-predicted time courses
      of [14C]DG and its metabolites were similar. Whole-brain glucose utilization
      (CMRglc) calculated with the TH or 3K Model, approximately 75 mumol 100 g-1 min
      1, was similar to values previously determined by model-independent techniques,
      whereas CMRglc calculated with the 4K Model was 44% higher. In a separate group
      of rats administered a programmed infusion to attain a constant arterial
      concentration of [14C]DG that minimizes effects of tissue heterogeneity as well
      as any product loss, CMRglc calculated with all three models was 79 mumol 100 g-1
      min-1 at 45 min after initiation of the infusion. Statistical comparisons of
      goodness of fit of total tissue radioactivity were, therefore, not indicative of
      which models best describe the tissue precursor and product pools or which models
      provide the most accurate rates of glucose utilization.

PMID- 7714007
TI  - Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain
      activation: evidence obtained with the Kety-Schmidt technique.
AB  - Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen
      (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest
      and during cerebral activation induced by the Wisconsin card sorting test.
      Measurements were performed in healthy volunteers using the Kety-Schmidt
      technique. Global CMRO2 was unchanged during cerebral activation, whereas global
      CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen
      to glucose consumption from 6.0 during baseline conditions to 5.4 during
      activation. Data obtained in the period following cerebral activation showed that
      the activation-induced resetting of the relation between CMRglc and CMRO2
      persisted virtually unaltered for > or = 40 min after the mental activation task
      was terminated. The activation-induced increase in cerebral lactate efflux
      measured over the same time period accounted for only a small fraction of the
      activation-induced excess glucose uptake. These data confirm earlier reports that
      brain activation can induce resetting of the cerebral oxygen/glucose consumption
      ratio, and indicate that the resetting persists for a long period after cerebral
      activation has been terminated and physiologic stress indicators returned to
      baseline values. Activation-induced resetting of the cerebral oxygen/glucose
      uptake ratio is not necessarily accounted for by increased lactate production
      from nonoxidative glucose metabolism.

PMID- 7714008
TI  - Analysis of PET neurofunctional mapping studies.
AB  - In this work, we present a method for analyzing positron emission tomography
      (PET) functional mapping experiments. The method is useful for identifying
      statistically significant differences between two PET data sets. First, uniform
      variance Z-images are created and then the statistical uncertainty in region-of
      interest values are calculated using a previously published method. The Z-images
      are calculated from the emission sinograms only--the calculation does not use
      scanner normalization and attenuation corrections and hence variance from these
      sources is eliminated, with no decrease in validity. Next, the Z-images are
      analyzed for activation sites using two separate techniques: a cluster analysis
      method and a change distribution analysis method. Both of these techniques are
      shown to be effective for objectively locating significantly activated regions
      from the Z-images. Two advantages of these methods are that they are objective
      and efficient; all of the parameters necessary in the calculations can be
      precomputed and stored since they depend only upon the geometry of the scanner.

PMID- 7714009
TI  - Long-term spatial cognitive impairment following middle cerebral artery occlusion
      in rats. A behavioral study.
AB  - Behavioral changes in the chronic phase of permanent occlusion of the right
      middle cerebral artery (MCA) in rats were investigated. One month after MCA
      occlusion, 23 rats were unable and 7 rats were able to solve a radial 8-arm maze
      task during a 1-month period. Three months after occlusion, 19 MCA-occluded rats
      failed to solve the task successfully again during at least a 1-month period (the
      cognitively impaired rats), and 11 MCA-occluded rats were able to solve it (the
      cognitively unimpaired rats). When a delay of 60 min was imposed for this task,
      five cognitively unimpaired rats failed to solve it. The locomotor activity of
      the cognitively impaired rats increased significantly 2 months after occlusion,
      and this increase showed good correlation with spatial cognitive deficit.
      However, the mean time a rat spent at each arm remained unchanged among the
      cognitively impaired, unimpaired, and sham-operated rats. There was no
      significant difference in the ratio between the cognitively impaired and
      unimpaired rats for disturbed motor coordination. These results suggest that MCA
      occlusion is capable of producing long-term spatial cognitive disturbance in
      rats. In addition, this spatial cognitive deficit does not seem to be primarily
      due to hypermotility or a disturbance in motor coordination.

PMID- 7714011
TI  - Contribution of cerebrovascular parasympathetic and sensory innervation to the
      short-term control of blood flow in rat cerebral cortex.
AB  - In two groups of normotensive rats anaesthetised with halothane, either the
      nasociliary nerve (NCN) or the NCN and parasympathetic (PS) fibres together (NCN
      PS) were functionally blocked at the right ethmoidal foramen. Blocking was
      achieved reversibly and repeatedly using a cooling probe. Cortical regional CBF
      (rCBF) was measured bilaterally using laser-Doppler probes. In Group 1, bilateral
      common carotid occlusion (CCO) was applied for 1 min both with and without block.
      In Group 2, CCO was applied permanently followed by stages of controlled
      haemorrhagic hypotension to deepen the ischaemia and the block applied at each
      stage. In Group 1, during CCO, rCBF was unaffected by blocking NCN-PS. However,
      during the transient postocclusive hyperaemia, blocking NCN-PS, but not NCN
      alone, significantly increased right side rCBF. In Group 2 and in Group 1 in the
      absence of CCO (normotension), rCBF was unaffected by blocking either set of
      fibres. We conclude that neither NCN nor PS fibres contribute to the tonic level
      of rCBF or to its autoregulatory control, but PS fibres conduct impulses tending
      to resolve postischaemic hyperaemia. We suggest that a subpopulation of PS fibres
      containing neuropeptide Y is activated under conditions of supernormal rCBF.

PMID- 7714010
TI  - D2 receptor blockade by flunarizine and cinnarizine explains extrapyramidal side
      effects. A SPECT study.
AB  - Twenty-six patients under treatment with the calcium channel blockers flunarizine
      (Fz) or cinnarizine (Cz) were examined-with single-photon emission computed
      tomography using [123I]iodobenzamide as a ligand. The striatal dopamine D2
      receptor-binding potential was determined and found to be reduced by 14 to 63%
      (39.5 +/- 15.0%; p < 0.0001) in patients compared with age-matched control
      values. This reduction was larger in 12 patients with extrapyramidal symptoms and
      was only slowly reversible after discontinuation of treatment. Patients treated
      for > 6 months had significantly larger reductions than patients treated for a
      shorter period. Parkinsonian symptoms were only seen in patients older than 50
      years. Our findings prove a neuroleptic-like action of Fz and Cz, which seems to
      be the major reason for their extrapyramidal side effects. Older age and long
      term treatment are predisposing factors for these effects.

PMID- 7714012
TI  - Differential effects of alcohols on intracerebral arterioles. Ethanol alone
      causes vasoconstriction.
AB  - We compared the effect of the acute application of ethanol, methanol, 1-propanol,
      1-butanol, urea, and mannitol (1-100 mM) on the basal tone of isolated-cannulated
      rat intracerebral arterioles to determine if the response of these arterioles to
      ethanol could be attributed to alteration of membrane fluidity or changes in
      osmolality. These arterioles spontaneously developed tone to 62.0 +/- 8.4% of
      passive diameter (44.2 +/- 11.9 vs. 70.9 +/- 14.7 microns). Ethanol caused a dose
      dependent reduction in arteriolar diameter starting at 3 mM (p = 0.03), reaching
      a diameter of 81.4 +/- 3.0% of basal tone at 100 mM. In comparison, all other
      agents tested caused the arterioles to dilate, with the exception of 1-propanol,
      which produced inconsistent vessel responses. At 100 mM concentration, methanol,
      1-butanol, urea, and mannitol dilated intracerebral arterioles by 116.1 +/- 12.7,
      151.5 +/- 12.4, 131.1 +/- 17.0, and 149.8 +/- 6.6%, respectively. Thus, in a
      concentration range associated with acute intoxication, ethanol causes
      constriction of isolated intracerebral arterioles. The mechanism of action of
      ethanol cannot be accounted for solely based upon its physicochemical
      characteristics of osmolality or lipid solubility, but rather may reflect a more
      specific action on one or more cellular mechanisms responsible for determining
      basal intracerebral arteriolar tone. The characterization of the response of
      intracerebral arterioles to ethanol is important in view of epidemiologic links
      between ethanol consumption and cerebrovascular disease.

PMID- 7714013
TI  - The contribution of delta 1- and delta 2-opioid receptors to hypoxia-induced pial
      artery dilation in the newborn pig.
AB  - Previously, it has been observed that mu-opioid receptors contribute to while
      kappa-opioid receptors oppose pial artery dilation in response to hypoxia. The
      present study was designed to investigate the contribution of delta 1- and delta
      2-opioid receptor activation to hypoxia-induced pial vasodilation. Newborn pigs
      equipped with a closed cranial window were used to measure pial artery diameter
      and collect cortical periarachnoid CSF for assay of opioids. Hypoxia increased
      CSF leucine enkephalin (a delta -agonist) from 36 +/- 6 to 113 +/- 17 pg/ml (n =
      5). Hypoxia-induced pial artery vasodilation was attenuated during moderate
      hypoxia (PaO2 approximately 35 mm Hg), while this response was blunted during
      severe hypoxia (PaO2 approximately 25 mm Hg), by the delta 1-opioid receptor
      antagonist 7-benzylidenenaltrexone (BNTX; 10(-8) M) (23 +/- 2 vs. 13 +/- 2 and 34
      +/- 6 vs. 10 +/- 3% for moderate and severe hypoxia in the absence and presence
      of BNTX, respectively; n = 5). In contrast, the delta 2-opioid receptor
      antagonist naltrindole (10(-9) M) blunted pial vasodilation during moderate
      hypoxia, but only attenuated the vasodilator response during severe hypoxia (22
      +/- 2 vs. 8 +/- 2 and 33 +/- 4 vs. 23 +/- 4% for moderate and severe hypoxia in
      the absence and presence of naltrindole, respectively; n = 5).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7714014
TI  - Persistent and massive gastrointestinal hemorrhage.

PMID- 7714016
TI  - Authentic health care reform.

PMID- 7714015
TI  - The Human Genome Project: who's looking out for ELSI? Ethical, legal and social
      implications.

PMID- 7714017
TI  - Long PR interval after whiplash injury.

PMID- 7714018
TI  - Case in point. Pseudohyperkalemia secondary to thrombocytosis.

PMID- 7714021
TI  - New thoughts on attention-deficit/hyperactivity disorder.

PMID- 7714020
TI  - Computerized medical records: one office's experience.

PMID- 7714022
TI  - Persistent fever and flank discomfort in a young woman.

PMID- 7714019
TI  - Advances in Wegener's granulomatosis.
AB  - The upper airway is usually the source of initial concern, but lung involvement
      eventually emerges. Thus, the disease is a reminder that the diagnosis of
      persistent upper airway problems should have more than a regional focus.
      Combinations of glucocorticoids and cytotoxic drugs have yielded a dramatic
      improvement in survival.

PMID- 7714024
TI  - An asymptomatic lung nodule in an elderly woman with joint pain.

PMID- 7714023
TI  - Defusing status epilepticus.
AB  - The risk of brain neuron death supersedes that of physical harm due to muscle
      spasms. In fact, immediate induction of neuromuscular paralysis impedes
      monitoring of anticonvulsant therapy, which can be empiric but should follow a
      predetermined, sequential protocol so that seizures can be terminated quickly.

PMID- 7714025
TI  - Progress in the immunogenetics of rheumatoid arthritis.
AB  - Although much remains to be learned about environmental factors and putative
      pathogens, significant strides have been made on the genetic front. Genes appear
      to have a greater role in determining disease severity than disease risk. In
      particular, patients who are heterozygous for two HLA-DR4 subtypes are prone to
      severe erosive disease, making them candidates for early, aggressive therapy.

PMID- 7714026
TI  - Oral contraceptives: an update.
AB  - Despite continual improvement in oral contraceptive formulations, many women
      still have unwarranted concerns about their safety and remain ignorant of their
      nonreproductive health benefits. The need for a reliable method of contraception
      is the greatest among adolescents and women older than 35 years--the two groups
      in the United States with the highest abortion rates.

PMID- 7714027
TI  - Behavior problems in preschool children: a review of recent research.
AB  - Research on the prevalence, course, and correlates of behavior problems in
      preschool children was examined. Prospective epidemiological studies and follow
      up studies of clinical/high risk samples indicate that serious externalizing
      problems identified early often persist. Negative, inconsistent parental behavior
      and high levels of family adversity are associated with the emergence of problems
      in early childhood and predict their persistence to school age. Studies are
      examined from a developmental perspective and integrated with research on optimal
      parent-child relationships. The severity of initial problems and family context
      are related to different developmental outcomes.

PMID- 7714028
TI  - Children and arithmetic.
AB  - The development of children's understanding of mathematical relations and of
      their grasp of the number system is described. It is discussed that children
      easily recognise one-way part-part relations but that the number system at first
      causes them difficulty. Children's relational understanding allows them to solve
      addition and subtraction problems fairly well when these deal with simple
      increases and decreases in quantity. It also helps them to make proportional
      judgements when these involve part-part relations. However, problems that involve
      relations between parts and wholes are at first extremely difficult. The review
      also deals with the effects of context and shows the considerable aptitudes that
      are handed on to children in informal settings.

PMID- 7714029
TI  - Genetics and children's experiences in the family.
AB  - Genetic research may have its greatest impact for clinicians and developmental
      researchers in terms of understanding the environment and how the environment
      relates to children's development. This review focuses on one example at the
      interface between nature and nurture. Recent research using diverse genetic
      designs shows that family environment as it is currently assessed involves a
      substantial contribution from genetic factors. Genetic factors also contribute to
      correlations between measures of the family environment and developmental
      outcomes. Implications of these findings are discussed.

PMID- 7714030
TI  - Individual differences in infancy and later IQ.
AB  - In recent years it has been demonstrated that cognitive development from infancy
      to later childhood displays some degree of (correlational) continuity. Studies
      that have demonstrated this continuity are reviewed, focusing on measures of
      visual information processing, means-ends problem-solving and other cognitive
      indices of infant performance. Models of continuity are described and evaluated,
      and the relevance of the findings and models to the Nature-Nurture issue are
      considered, with particular attention to the related issues of the role of
      experience in early life, and the extent to which infant development is
      canalized. Theoretical and practical applications of the research are discussed.

PMID- 7714031
TI  - A recombinant human immunodeficiency virus type-1 capsid protein (rp24): its
      expression, purification and physico-chemical characterization.
AB  - An expression system has been established in Escherichia coli to facilitate the
      preparation of the HIV-1 capsid protein in amounts sufficient for structural
      analysis. A plasmid vector pTCA5, containing the gene for the recombinant HIV-1
      capsid protein rp24 under the control of the lambda-PR-promoter, was constructed
      which gave an expression product that spanned 234 amino acid residues. It differs
      at the N-terminus from the authentic sequence in that the residues Pro-Ile- are
      replaced by Met-Asn-Ser-Ala-Met-. Recombinant p24 was produced, as inclusion
      bodies in E. coli LE392 containing pTCA5, at a level of approximately 15% of the
      total cellular protein. After dissolution of the inclusion bodies in the acidic
      urea system, the protein was easily reconstituted in a soluble state by dialysis.
      The yield of reconstituted and purified protein was 12 mg per liter in rich
      medium. Recombinant rp24 consists of about 40% alpha-helix and 10% beta-sheet
      from circular dichroism measurements and the two cysteine residues, within the
      rp24 sequence, are bridged by a disulfide bond.

PMID- 7714033
TI  - A hemi-nested PCR assay for the detection and identification of vesicular
      stomatitis virus nucleic acid.
AB  - This paper is the first to describe the development of a hemi-nested PCR assay
      for the detection of vesicular stomatitis virus (VSV) nucleic acid. This assay
      was developed as it combines high sensitivity for virus genome detection with the
      identification of the external amplification product in the reamplification step,
      thus confirming the specificity of the reaction. The assay did not depend on the
      presence of infectious virus in samples, as demonstrated by its detection of VSV
      in blood samples which were non-infectious in tissue culture. One further
      advantage was that the VSV-New Jersey and VSV-Indiana serotypes could be
      differentiated through the selective use of the appropriate hemi-nested primer.
      This assay is ideal for the study of VSV pathogenesis and persistence.

PMID- 7714032
TI  - Double-nested polymerase chain reaction for detection of caprine arthritis
      encephalitis virus proviral DNA in blood, milk, and tissues of infected goats.
AB  - A nested polymerase chain reaction (PCR) for detecting proviral DNA of caprine
      arthritis-encephalitis virus (CAEV) in biological samples was developed. Primers
      for both gag and pol sequences of the CAEV genome were included in a single tube
      for simultaneous amplification ('double' PCR), and the resulting bands were
      resolved visually in ethidium bromide-stained agarose gels. Internal gag and pol
      probes were used to verify the identity of the amplified products by non
      radioactive Southern hybridization. Final confirmation of the identity of
      representative PCR bands was provided by DNA sequence analysis. A comparison
      between the PCR and an antibody ELISA (with recombinant CAEV p28 as target) using
      141 caprine blood samples indicated very strong agreement between the two assays
      (kappa = 0.912). Four of 7 goats with indeterminate ELISA results were PCR
      positive as were 5 of 40 (12.5%) seronegative goats, most probably indicating
      delayed seroconversion. Eleven of 27 goats (41%) PCR-positive on blood had
      detectable CAEV proviral DNA in milk. Proviral DNA was also detected in lung,
      mesenteric lymph node, bone marrow, synovial membrane, and mammary gland of a
      seropositive, clinically affected goat, but not in equivalent tissues of a
      healthy seronegative goat.

PMID- 7714036
TI  - Serotyping of human astrovirus strains by immunogold staining electron
      microscopy.
AB  - Human astrovirus strains were propagated in CaCo-2 cell cultures, and virus
      multiplication was demonstrated by immunosorbent electron microscopy (ISEM).
      Serotyping of the virus strains was carried out in cell culture fluids or
      directly in faecal extracts by an indirect immunogold staining (IGS) electron
      microscopy technique, using specific rabbit antisera against astrovirus types 1-6
      as primary antibodies and goat anti-rabbit IgG gold conjugate as secondary
      antibody. Thirty-seven astrovirus strains were examined, of which 26 grew in the
      cell cultures in several passages. IGS of the cell-derived viruses showed that
      16, 3, 3, and 4 of the strains were types 1, 2, 3, and 4 respectively. Types 5
      and 6 were not demonstrated. Eleven strains did not grow in cell cultures, and
      attempts to serotype these strains by IGS directly in the faecal extracts were
      unsuccessful, except for one strain which was found to be type 1. The results
      indicate that IGS may be a specific and suitable method for serotyping
      astroviruses grown in cell cultures.

PMID- 7714035
TI  - A touchdown PCR for the differentiation of equine herpesvirus type 1 (EHV-1)
      field strains from the modified live vaccine strain RacH.
AB  - More than 50 reference strains and field isolates of equine herpesvirus type 1
      (EHV-1) were examined by a touchdown PCR. Primers for specific amplification of
      EHV-1 DNA were chosen from the terminal and internal repeat regions of the EHV-1
      genome where the high-passaged live vaccine strain RacH displays symmetric 850 bp
      deletions. The positive strand and one negative strand primer were designed to
      encompass the deletions present in RacH, and the second negative strand primer
      was designed to hybridize within these deletions. Discrimination between field
      isolates and the vaccine strain was achieved by the generation of amplification
      products of different size: In all EHV-1 reference strains and field isolates, a
      495 bp DNA fragment was amplified specifically, whereas a 310 bp fragment was
      amplified when DNA of the vaccine strain RacH was used as a template. PCR
      amplification was only obtained in the presence of 8-10% dimethylsulfoxide and
      when the primer annealing temperatures were decreased stepwise from 72 degrees C
      to 60 degrees C. Under these conditions as little as 100 fg template DNA,
      corresponding to about 100 genome equivalents, could be detected. The PCR assay
      allows fast and sensitive discrimination of the modified live vaccine strain RacH
      from field strains of EHV-1 since it is applicable to viral DNA extracted from
      organ samples and paraffin-embedded tissues. It may thus be helpful for examining
      the potential involvement of the RacH live vaccine strain in abortions of
      vaccinated mares.

PMID- 7714037
TI  - Serotype-specific detection of bean common mosaic potyvirus in bean leaf and seed
      tissue by enzymatic amplification.
AB  - An assay involving reverse transcription and polymerase chain reaction (PCR) is
      described for specific detection of serotypes A and B BCMV isolates in bean leaf
      and seed tissues. Three oligonucleotide primers designed according to the
      sequence data available allow, in appropriate combination, serotype-specific
      detection of BCMV. The sensitivity of the method was sufficient to detect BCMV in
      as little as 100 fg and 50 pg of infected leaf and seed tissues, respectively.

PMID- 7714034
TI  - Accurate and differential quantitation of HIV-1 tat, rev and nef mRNAs by
      competitive PCR.
AB  - An accurate method is described for measuring the relative abundance of HIV-1
      regulatory mRNAs directly in clinical specimens. Specimen RNA is reverse
      transcribed and coamplified with a common competitor containing tat, rev and nef
      internal standards using fluorescent primers and a competitive polymerase chain
      reaction. After amplification, individual products are separated and analyzed on
      a fluorescent DNA sequencer. Using this approach, it was possible to measure
      reproducibly two-fold differences in the relative abundance of mRNAs with coding
      potential for tat, rev and nef from as little as 0.2 ng of total RNA extracted
      from peripheral blood mononuclear cells of HIV-1 infected persons. The ratio
      method eliminates the need to account for variability in RNA recovery during
      sample processing and provides a powerful tool for measuring the differential
      expression of HIV-1 regulatory genes in vivo.

PMID- 7714038
TI  - Factors affecting the efficiency of immunogold labelling of plant virus antigens
      in thin sections.
AB  - Sections of pellets of six purified plant viruses with three different
      morphologies were used to examine different technical aspects of the immunogold
      labelling (IGL) technique. The results showed that fixation by glutaraldehyde
      alone was better than with osmium tetroxide post-fixation, and that Decon 75 was
      the best of the pretreatments tried. The study showed that different virus
      homologous antisera gave different results in IGL tests, and that longer
      incubation times with both antiserum and gold probe gave higher label densities
      without any increase in background label. Also, cross-absorption of the virus
      antisera with healthy host protein before use gave cleaner backgrounds and thus
      higher specificity. The work also examined the relationship between label density
      and amounts of visible virus. There was no correlation between the numbers of
      virus particles seen in sections and the numbers of gold particles; moreover,
      there was no apparent relationship between label density and the orientation or
      distribution of the virus particles in the section. The role of the embedding
      resin and its polymerisation temperature are also discussed.

PMID- 7714039
TI  - IgM antibody capture haemadherence test (MACHAT) for the detection of measles
      specific IgM.
AB  - An antibody capture haemadherence test (MACHAT) for detecting measles-specific
      IgM is described. The assay is based on the antibody capture principle with
      rhesus monkey erythrocytes as detector system in place of labelled antisera.
      MACHAT was compared with a commercial indirect enzyme immunoassay (EIA) for
      measles-specific IgM using 382 sera from patients notified as measles. There was
      good agreement between the two tests; 106 sera were found to contain measles IgM
      by both tests, 7 further sera were positive only in the commercial EIA and 9 only
      in MACHAT. One sera gave an equivocal result in MACHAT and another in the
      commercial EIA. Twelve of the 18 sera with discrepant results were also tested by
      MACRIA; in 7 MACRIA gave the same results as MACHAT, in 3 the MACRIA results
      agreed with the commercial test and in 2 the MACRIA results were equivocal.
      Specificity was established by a lack of MACHAT reactivity in sera collected from
      blood donors (n = 83) and from cases of recent rubella, dengue and parvovirus B19
      infection (n = 51). The MACHAT is a simple, cheap test that can be read by eye
      and is suitable for measles surveillance programmes in the developing world.

PMID- 7714040
TI  - Comparison of two hybridization assays for the rapid detection of PCR amplified
      HSV genome sequences from cerebrospinal fluid.
AB  - Rapid diagnosis of herpes simplex encephalitis (HSE) can only be achieved by the
      polymerase chain reaction (PCR). In order to carry out PCR under routine
      conditions, it is of great importance to establish an easy DNA extraction
      protocol and especially a rapid and sensitive DNA detection method. In the
      present study, two different solid phase hybridization assays (Gen-Eti-K-DNA
      Enzyme Immunoassay (DEIA), Sorin Biomedica, Italy and Enzymun-Test DNA detection,
      Boehringer Mannheim, Germany) were compared for detection of PCR amplified HSV
      DNA polymerase genome region, using standard primers, from cerebrospinal fluid
      (CSF) samples. 122 CSF samples obtained from patients suffering from encephalitis
      and hospitalized at the University Clinics of Frankfurt and Graz during the
      period January 1992 to July 1993 were tested. To ascertain the sensitivity of the
      hybridization assays, dilution series of a plasmid, encoding the amplified region
      of the polymerase gene, were investigated. The detection limit of the DEIA assay
      was one copy of the plasmid/microliter, and the lowest amount of DNA which could
      be detected by the Enzymun assay as well as Southern blot was 10
      copies/microliter. 15 CSF samples obtained from patients with HSE were found
      positive by the three assays. Concordant results were also obtained with CSF
      samples from non-HSE patients. The results of this study show that new
      hybridization systems guarantee a fast and high-sensitive detection of amplified
      HSV DNA. HSV PCR in CSF can be carried out routinely by the combined use of rapid
      hybridization and a simple extraction procedure.

PMID- 7714041
TI  - Use of recombinant pp38 antigen of Marek's disease virus to identify serotype 1
      specific antibodies in chicken sera by western blotting.
AB  - A fowlpox recombinant expressing the pp38 antigen of Marek's disease virus has
      been constructed. Production of pp38 in chick embryo fibroblasts (CEF) infected
      at a m.o.i. of 1 pfu/cell occurred over a period of 5 days and reached a peak at
      72 h after infection. The pp38 antigen could be released from infected cells by
      freezing and thawing. Western blot analysis showed that denatured pp38 antigen
      reacted with antisera from chickens inoculated with serotype 1 MDV but failed to
      react with antisera from chickens inoculated with MDV serotype 2 or HVT. The
      results suggest that MDV pp38 contains a serotype 1-specific epitope which
      becomes available upon denaturation of the antigen and that this could be
      exploited to identify MDV-specific antibodies in epidemiological studies. The
      relationship between pp38 and the related polypeptides pp24 and pp41 in MDV
      infected cells was also examined. The results suggest that pp24 and pp38 are
      synthesised independently and that MDV coded proteins (probably a protein kinase)
      might be required to convert pp38 to pp41.

PMID- 7714042
TI  - Improvement in the sensitivity of PVYN detection by increasing the cDNA probe
      size.
AB  - Cloned cDNA to a North American isolate of tobacco veinal necrotic strain of
      potato virus Y (PVYN) RNA was used for the detection of PVYN in diseased samples.
      Digoxigenin-labelled cDNA probes were prepared from approximately 0.56 kb,
      approximately 1.2 kb, approximately 2.5 kb, and approximately 3.25 kb overlapping
      clones representing the 3'-terminus of the PVYN genome. It was shown that the
      probe sizes, as determined by alkaline gel-electrophoresis, generally
      corresponded to the size of the template cDNA used. The sensitivity of detection
      of PVYN was maximum using the largest probe and the sensitivity generally
      decreased with a decrease in probe size. Five pg of homologous purified PVYN RNA
      was detected with the approximately 3.25 kb probe, and 1000 pg of PVYN RNA was
      required for the approximately 0.56 kb probe. The different levels of sensitivity
      of detection were also apparent when crude nucleic acid extracts from PVYN and
      PVYO infected plants were used. In comparison with tobacco bioassay, and dot
      immunobinding assay nucleic acid hybridization was found to be more sensitive.

PMID- 7714043
TI  - Quantification of latent Mamestra brassicae nuclear polyhedrosis virus in M.
      brassicae insects using a PCR-scintillation proximity assay.
AB  - A laboratory culture of Mamestra brassicae insects (MbLC) was found to harbour a
      latent baculovirus infection. The copy number of the occult MbNPV genome in both
      the MbLC larvae, and in a cell line derived from the fat body of MbLC was
      determined by the use of a rapid and convenient PCR-scintillation proximity assay
      (SPA). The SPA system relies on the use of fluomicrospheres (SPA beads) coated
      with acceptor molecules which are capable of binding radiolabelled ligands in
      solution. In the assay described, a biotinylated PCR primer is used and [3H]dNTPs
      are incorporated into the amplified DNA. The SPA beads are coated with
      streptavidin, and after binding the biotinylated primer, any amplified,
      radiolabelled DNA will activate the fluor. The amount of amplified DNA from the
      target sequence can then be directly quantified using a scintillation counter.
      The number of MbNPV genomes present in a persistently infected M. brassicae cell,
      as proposed by SPA, suggest between 13 and 20 copies of the viral genome may be
      present in individual fat body cells.

PMID- 7714044
TI  - Detection of an unidentified potyvirus from Roystonea regia palm using the
      polymerase chain reaction and degenerate, potyvirus specific, primers and
      potential problems arising from the amplification of host plant DNA sequences.
AB  - Degenerate potyvirus-specific primers were used in the PCR to amplify cDNA
      representing a 335 nucleotide region of the coat protein gene in RNA purified
      from an uncharacterised potyvirus isolated from Roystonea regia palms in
      Queensland, Australia. The RNA was also detected by PCR in total nucleic acid
      extracts from infected Nicotiana benthamiana, N. clevelandii and Vicia faba. The
      method also successfully detected pea seed-borne mosaic virus in Pisum sativum.
      In addition the procedure amplified DNA's of approximately 200 bp and 420 bp, of
      non-viral origin, from total nucleic acid extracts of healthy Nicotiana spp,
      indicating that size of the PCR products needs to be included as a criterion for
      identifying virus specific products when this method is used.

PMID- 7714045
TI  - Detection of human T-cell leukaemia virus 1 permissive cells using cell lines
      producing selectable recombinant virions.
AB  - A selectable retrovirus vector based on a full length HTLV-1 provirus clone, pCS
      HTLV-1, was constructed by replacing the coding regions for tax, rex and the 3'
      region of env with the prokaryotic neomycin resistance gene under the control of
      the CMV promoter. This vector, pHTLV-1-CMVneo, was transfected into HTLV-1
      infected human lymphocytes and fibroblasts. The production of recombinant virus
      by these cells was measured by the transfer of G418 resistance to target cells.
      Infection of target cells showed a preference for human lymphocytes in addition
      to two human fibroblast cell lines, Hos7 and RD4, and the African green monkey
      kidney cell line, Cos7. This system provides a method to study the cellular
      tropism of HTLV-1 and additionally provides a model to facilitate molecular
      studies of the natural events of HTLV-1 infection and integration.

PMID- 7714046
TI  - Polyacrylamide gel electrophoresis of viral genomic RNA as a diagnostic method
      for infectious pancreatic necrosis virus detection.
AB  - A rapid and simple technique for the diagnosis of IPNV from cell culture and
      infected fish tissues has been developed. It is based on the observation of IPNV
      bisegmented double-stranded RNA genome in silver stained polyacrylamide gels
      after electrophoresis. The method is highly specific and can detect as little as
      1 ng of viral RNA, which corresponds to 1 x 10(5) pfu, making it possible to
      visualize the viral genome as soon as the initial cythopatic effect appears.
      Furthermore, the RNA viral genome could be detected directly from fish tissues
      when fish showed clear clinical signs of the disease. The method has the
      advantage of detecting any strain of IPNV. An acrylamide concentration of 6% and
      bisacrylamide concentration of 0.13% give a rapid and definitive result in less
      than 6 h.

PMID- 7714047
TI  - Increased viral titers and enhanced reactivity of antibodies to the spike
      glycoprotein of murine coronavirus produced by infection at pH 6.
AB  - Infection of cell monolayers by murine coronavirus A59 at pH 6 rather than 7
      yielded a ten-fold increase in the infectious titer and a remarkable enhancement
      of the reactivities of monoclonal and polyclonal antibodies against the spike
      glycoprotein in immunoblotting, immunoprecipitation and enzyme-linked
      immunosorbent assays. These observations are very useful for detecting antibodies
      against the S glycoprotein of coronaviruses and enhancing infectious titers.

PMID- 7714048
TI  - Recovery of a rare clone from a population of unstable retroviral vector
      expressing mammalian cells using a new RNA extraction and slot-blot protocol.
AB  - Although a useful and important method of gene transfer, retroviral vectors can
      be genetically unstable. In the course of experiments using DOEJS, a retroviral
      vector able to confer expression of a H-ras oncogene and a neomycin resistance
      gene (neo) on mammalian cells (Compere et al., 1989), it was found that the vast
      majority of infected rat embryo fibroblasts, recovered on the basis of neo
      activity (i.e., G418 resistance), did not express ras mRNA. It was subsequently
      observed that most cells in the psi 2 cell line used to propagate DOEJS failed to
      produce virus capable of expressing both ras and neo in primary rat embryo
      fibroblasts. A simplified RNA extraction and slot-blot technique was developed to
      screen mRNA from several hundred fibroblast clones and, in doing so, infected
      fibroblast clones producing both neo and ras mRNA were identified at low
      frequency. The DOEJS/psi 2 packaging line was subsequently subcloned and
      individual clones screened for their ability to confer appropriate gene
      expression on target cells. Subclone DOEJS/psi 2-B6 was eventually isolated after
      screening 24 DOEJS subclones and 240 infected rat embryo fibroblast colonies.
      DOEJS/psi 2-B6 was shown to induce reliably phenotypic transformation, G418
      resistance, and ras and neo mRNA expression in primary rat embryo fibroblasts.
      The RNA extraction and screening procedure was thus useful for recovering an
      infrequent subclone producing a retrovirus with the original properties.

PMID- 7714049
TI  - SIV- and HIV-2-neutralising antibodies in infected macaques measured by a novel
      and simple neutralisation test based on a non-commercial antigen-ELISA.
AB  - A method for the measurement of neutralising antibodies (nab) directed against
      SIVmac or HIV-2 was developed. The assay is based on antigen detection using a
      non-commercial enzyme-linked immunosorbent assay (ELISA). Studies were carried
      out to determine the influence of the test conditions on the nab titre. The
      sensitivity of the assay depended mainly on the virus dose and the length of
      incubation of the serum-virus-mixture. Prolongation of the culture time from 9 to
      11 days increased the validity of the results. Applying this neutralisation assay
      on sequential serum samples from SIV mac- or HIV-2ben-infected macaques, a
      considerable variation was found in nab titres between individual animals.
      Whereas after infection with SIVmac, in vitro-neutralisation seems to correlate
      with protection against disease, and the lower pathogenity of HIV-2ben in
      macaques compared with SIVmac is not due to the differences in nab titres.

PMID- 7714051
TI  - Quantification of adenovirus particles.
AB  - A physical method for quantification of the adenovirus was tested. It implies a
      centrifugation of the clarified or chloroform- (or freon-) treated crude virus
      suspension (0.5 ml) in a gentle sucrose gradient, following the analysis in a
      sensitive UV flow photometer and calculation of virus mass. The result
      (micrograms/ml) is obtained after about 1 h. The sensitivity of detection at
      wavelength 254 nm, 278 nm and 226 nm was compared. Virus yield of several
      serotypes from monolayer cultures of FL-cells was determined in a range of < 0.1
      to 7 micrograms/ml. The ratio of infectious to physically complete virus (about
      the 770S component), the influence of freezing and thawing, storing at 4 degrees
      C and the effectiveness of concentration steps were also determined. There was no
      significant difference between the sucrose density gradient method (sedimentation
      rate) and the density equilibrium ultracentrifugation in a CsCl gradient.

PMID- 7714050
TI  - Quantitation of latency established by attenuated strains of Pseudorabies
      (Aujeszky's disease) virus.
AB  - A quantitative and differential polymerase chain reaction (PCR) was developed
      that measures the ability of Pseudorabies virus (PRV) to colonize tissues that
      are targets for latency. This PCR is based on the co-amplification of viral
      target sequences and that of a gene of the host species: the porcine Nuclear
      Factor 1 gene, which serves as an internal standard. The technique was found to
      be sensitive and reproducible. Using this technique, individual variabilities
      were detected in the level of colonization of trigeminal ganglia established by a
      PRV strain among different animals. At a population level, it was established
      that two different PRV attenuated strains establish latency with different
      efficiencies, when applied by the same route and at similar inoculation dose.

PMID- 7714052
TI  - Rapid coagglutination test for the detection and typing of foot and mouth disease
      virus.
AB  - Protein A containing Staphylococcus aureus was used to develop a coagglutination
      (COA) test for the detection and typing of foot and mouth disease virus (FMDV) O,
      A and C serotypes in infected cells and tissues. Different batches and amounts of
      guinea pig anti-FMDV sera were assessed to optimize the preparation of COA
      conjugates. The sensitivity and specificity of the COA Test for the detection of
      FMDV O, A and C serotypes and heterologous viruses was also characterized.
      Comparison between the COA Test and complement fixation test for the detection
      and typing of FMDV obtained from extracts of tongue epithelial tissues from
      infected cattle revealed high agreement in the results and indicated a potential
      application of the COA Test for the direct diagnosis of viruses.

PMID- 7714053
TI  - Murine retroviral vector that induces long-term expression of HIV-1 envelope
      protein.
AB  - A retroviral vector was constructed that induces long-term expression of human
      immunodeficiency virus type 1 (HIV-1) rev, vpu and env genes. The vector contains
      the neo gene and a cytomegalovirus (CMV) immediate early promoter followed by HIV
      1 sequence. When HeLa cells were infected with viral stocks derived from this
      vector, about 25% of the resulting G418-resistant clones expressed HIV-1 envelope
      protein (Env), easily detectable by Western blot analysis, metabolic labelling,
      and syncytium formation after co-cultivation with HeLa-CD4 cells. In most cases
      the level of Env expression was higher than in a T cell line (H9) chronically
      infected with HIV-1. Env-expressing HeLa cell lines also expressed Rev, detected
      by transfection with a Rev-dependent CAT gene construct, and Vpu, detected by
      immunoprecipitation with a Vpu-specific antiserum. The 75% of G418-resistant HeLa
      cell lines that did not express Env were found to contain proviruses that had
      undergone deletion of env sequences corresponding to a known intron; presumably
      these cell lines arose as a result of infection with virions derived from spliced
      RNAs. This vector should be useful for studying non-transient effects of HIV Env,
      Rev and Vpu in tissue culture, and for the production of Env- and/or Rev
      expressing cell lines.

PMID- 7714055
TI  - Optimization of PCR and automated sequencing of clinical isolates of respiratory
      syncytial virus.
AB  - A streamlined protocol was developed to carry out nucleotide sequence analysis on
      PCR products obtained from regions of the RNA genome of respiratory syncytial
      virus (RSV). Whole cell RNA extracted from tissue culture cells inoculated with
      RSV-infected nasopharyngeal aspirates was used as a template for single-tube cDNA
      synthesis and PCR amplification of specific regions of the RSV fusion (F) protein
      gene. The products were then purified using Sephacryl spin columns and digested
      using lambda-exonuclease to obtain single-stranded templates for analysis using
      dye-primer chemistry in an automated sequencer. Optimization of a range of
      parameters and comparison of a number of alternate procedures resulted in a final
      protocol that allowed the comparison of the sequences of a panel of local RSV
      subgroup A and B clinical isolates.

PMID- 7714054
TI  - Differential diagnosis of infectious laryngotracheitis from other avian
      respiratory diseases by a simplified PCR procedure.
AB  - A simple polymerase chain reaction (PCR)-based procedure was developed for the
      detection of avian infectious laryngotracheitis virus (ILTV) in chicken trachea,
      chorio-allantoic membrane (CAM), infected hepatoma cells and infectious cell
      culture supernatant. Samples were prepared by dilution in distilled water. After
      boiling and low speed centrifugation, samples were used for PCR analysis with two
      primers without special labeling. The PCR analysis for ILT virus could be
      completed in less than 8 h. Standard agarose gel electrophoretic analysis of the
      PCR products revealed a prominent band of 300 base-pairs in samples from ILTV
      infected specimens, but not from specimens containing Newcastle disease virus,
      infectious bronchitis virus, avian adenovirus, fowlpox virus, Pachecoz or Marek's
      disease virus. One single ILTV infected cell or 10 plaque forming units of ILTV
      could be detected with this procedure. The procedure can be used for the
      identification of ILTV and the differentiation of ILTV from other avian
      respiratory tract infectants.

PMID- 7714056
TI  - Evaluation of a 'one tube' reverse transcription-polymerase chain reaction for
      the detection of ruminant pestiviruses.
AB  - A 'one tube' reverse transcription-polymerase chain reaction ('one tube' RT-PCR)
      using rTth DNA polymerase was compared with an existing RT-PCR using Taq DNA
      polymerase (Taq RT-PCR) to detect ruminant pestiviruses in infected cell
      cultures. The technically simpler and more convenient 'one tube' method was
      relatively insensitive detecting only 11 of the 34 samples tested, all of which
      were positive by Taq RT-PCR.

PMID- 7714057
TI  - Chemiluminescent microwell hybridization assay for direct detection of human
      parvovirus B19 DNA.
AB  - A method for the direct detection of human parvovirus DNA in serum samples that
      uses a digoxigenin-labeled RNA probe to hybridize with target B19 DNA, followed
      by capture of the hybrid onto a microtiter plate wells previously coated with a
      second oligonucleotide probe was developed. The captured hybrid is then detected
      with anti-digoxigenin-alkaline phosphatase conjugate and chemiluminescent
      substrate and the reaction read on a scintillation counter. The relative
      sensitivities of the microwell and standard dot blot hybridization assays were
      compared. The chemiluminescent microwell hybridization assay was more sensitive
      than dot-blot hybridization and could be performed in a few hours. This format,
      therefore, permits rapid and sensitive detection of parvovirus DNA suitable for
      the clinical setting.

PMID- 7714058
TI  - Liquid-phase hybridization and capture of hepatitis B virus DNA with magnetic
      beads and fluorescence detection of PCR product.
AB  - The polymerase chain reaction (PCR) exceeds all hitherto known detection limits.
      This sensitivity could lead to false positive results. Every manipulation
      increases the risk of contamination via, for example, aerosols. Most protocols
      for the extraction of template nucleic acids are complicated and possible
      centrifugation steps do not reduce the risk of aerosols. In addition, most of the
      methods for analysis are time-consuming and cannot be applied to different
      template materials. An alternative extraction method has been developed. The fast
      chemical denaturation of template by guanidine thiocyanate was followed by liquid
      hybridization to biotinylated oligonucleotides. The template nucleic acid could
      be washed after binding to streptavidin-coated paramagnetic beads to reduce
      influence on the enzymatic amplification steps. PCR of hepatitis B virus
      deoxyribonucleic acid was used to demonstrate how easy, versatile, and time
      saving this method is without centrifugation. The level of extracted nucleic
      acids was quantitated and the properties for sensitive extraction were evaluated.
      After PCR an additional step was developed which used fluorescent staining to
      detect positive amplifications. This is useful to identify positive results in
      predominantly negative samples.

PMID- 7714059
TI  - Comparative analysis of serological markers of chronic delta infection: HDV-RNA,
      serum HDAg and anti-HD IgM.
AB  - To study the concordance, sensitivity and specificity of HDV-RNA determination by
      molecular hybridization, serum HDAg by immunoblot and anti-HD IgM by commercial
      enzyme immunoassay as compared to intrahepatic HDAg detection by an
      immunoperoxidase method, a statistical analysis was applied to the results of
      serum sample and liver biopsy determinations in 50 patients with chronic delta
      hepatitis (38 positive to tissue HDAg and 12 negative). Of the 38 patients with
      hepatic HDAg, HDV-RNA was found in 31 (82%), serum HDAg by immunoblot in 27 (71%)
      and anti-HD IgM in 33 (87%). Among the 12 patients without hepatic HDAg, one was
      found with serum HDAg using the immunoblot technique, two (17%) had HDV-RNA, and
      7 (58%) had anti-HD IgM. Serum HDAg determination by immunoblot was the most
      specific test, followed by HDV-RNA analysis. The least specific was the anti-HD
      IgM technique. The anti-HD IgM test was the most sensitive, followed by HDV-RNA
      and serum HDAg. The concordance with intrahepatic HDAg detection was highest for
      HDV-RNA determination, followed by HDAg in serum. The least degree of concordance
      was found with anti-HD IgM determination. These results suggest that the
      determination of HDV-RNA by the hybridization method can be of great value for
      the diagnosis and monitoring of chronic delta hepatitis.

PMID- 7714060
TI  - In situ hybridisation and in situ polymerase chain reaction detection of
      parvovirus B19 DNA within cells.
AB  - Modification of an in situ polymerase chain reaction (ISPCR) technique is
      described for the detection of B19 parvovirus infection. Specific amplification
      of B19 DNA inside fixed cells was followed by hybridisation with a digoxigenin
      labelled probe and then visualised by immunochemical reaction. The assay had
      higher sensitivity compared to direct in situ hybridisation and still allowed
      cellular localisation and characterisation of infected cells. This assay can be
      used as a confirmatory method for PCR in tissues and will allow further
      identification of tissues permissive for B19 parvovirus infection.

PMID- 7714062
TI  - Routine diagnosis of seven respiratory viruses and Mycoplasma pneumoniae by
      enzyme immunoassay.
AB  - A composite EIA, using 8-well microstrips, was used for the rapid detection of
      seven respiratory viruses and M. pneumoniae. The viruses included influenza A and
      B, parainfluenza 1, 2 and 3, adenovirus and respiratory syncytial virus. During
      the 61 month period--June 1988 to June 1993--17326 respiratory specimens,
      submitted from three states, were tested by this EIA. The specimens were mainly
      from a paediatric population (hospitals and private physicians). RSV was the
      predominant virus detected, followed by adenovirus, parainfluenza 3, M.
      pneumoniae, influenza A, parainfluenza 2, influenza B and parainfluenza 1. The
      use of blocking antibodies confirmed the identification of the agents, in
      particular with samples showing absorbance values greater than the cutoff with
      more than one infectious agent. Different methods for processing specimens in
      order to obtain a uniform suspension, and interpretation of non-specific
      reactions, are discussed. The assays showed an average sensitivity of 85% and
      specificity of 99%, compared to virus culture. This EIA system provided an
      efficient method for the rapid diagnosis of viral and mycoplasmal infections in a
      busy diagnostic laboratory.

PMID- 7714061
TI  - Polymerase chain reaction detection of type D simian retrovirus proviral DNA from
      infected macaques.
AB  - A simple polymerase chain reaction (PCR) approach was developed for detection of
      Type D simian retrovirus (SRV) serogroup 2 proviral DNA using peripheral blood
      lymphocytes (PBLs) obtained from infected macaques. PCR primer pairs were
      developed against serogroup 2 envelope (env) gene sequence, and fidelity of PCR
      fragment amplification was determined using molecularly cloned SRV serogroup 2
      (D2/RHE/OR) DNA, and genomic DNA from Raji cells independently infected with
      different SRV serogroups. One primer pair exhibiting high fidelity was then
      utilized for PCR detection of serogroup 2 proviral DNA from PBLs, and from cells
      sorted into immune cell subpopulations by fluorescent-activated cell sorting
      (FACS). Env PCR fragments were readily detected from as few as 10(4) PBLs or
      immune cell subpopulations. In addition, highly specific PCR primers against
      serogroups 1 and 3 were utilized to detect proviral DNA from Raji cells infected
      with SRV serogroups. In all cases, primers designed to amplify serogroups 1, 2,
      and 3 proviral DNA were specific for their intended serogroup. This primer
      information and development of a PCR approach for detection of specific SRV
      proviral DNA will be of potential utility as a rapid surveillance tool in
      monitoring type D simian retrovirus infection within Asian macaque colonies.

PMID- 7714063
TI  - Clinical review 68: The endocrine regulation of fetal growth in late gestation:
      the role of insulin-like growth factors.

PMID- 7714064
TI  - Vitamin D metabolism, aging, and bone loss.

PMID- 7714065
TI  - Prevention of bone loss by vitamin D supplementation in elderly women: a
      randomized double-blind trial.
AB  - The purpose of the study was to determine the effect of vitamin D supplementation
      on bone turnover and bone loss in elderly women. Three hundred forty-eight women,
      ages 70 yr and older, were randomized to receive 400 IU vitamin D3 per day (n =
      177) or placebo (n = 171), double-blind, for a period of 2 yr. Main outcome
      measures were bone mineral density of both hips (femoral neck and trochanter) and
      the distal radius, as well as biochemical markers of bone turnover. The effect of
      vitamin D supplementation was expressed as the difference in mean (percentage)
      change between the placebo group and the vitamin D group. The measurements were
      repeated in 283 women after 1 yr and in 248 women after 2 yr. Vitamin D
      supplementation significantly increased serum 25-hydroxyvitamin D (250HD) (+35
      nmol/L) and 1,25-dehydroxyvitamin D [1,25-(OH)2D] (+7.0 pmol/L) levels and
      urinary calcium/creatinine ratios (+0.5%) and significantly decreased PTH(1-84)
      secretion (-0.74 pmol/L) after 1 yr. No effect was found for the parameters of
      bone turnover. The effect on the bone mineral density of the left femoral neck
      was +1.8% in the first yr, +0.2% in the second yr, and +1.9% during the whole
      period (95% confidence interval 0.4, 3.4%). At the right femoral neck the effects
      were +1.5%, +1.1%, and +2.6% (confidence interval 1.1, 4.0%), respectively. No
      effect was found at the femoral trochanter and the distal radius. Supplementation
      with 400 IU vitamin D3 daily in elderly women slightly decreases PTH secretion
      and increases bone mineral density at the femoral neck.

PMID- 7714066
TI  - Extensive personal experience: gonadotroph adenomas.
AB  - Our experience with gonadotroph adenomas during the last 20 years has taught us
      how to recognize them by their size, neurologic symptoms, and inefficient and
      incomplete secretion of intact gonadotropins and their subunits. Treatment now is
      primarily by transsphenoidal surgery and secondarily by radiation. Future
      development of a pharmacologic treatment will likely await more detailed
      knowledge of their pathogenesis.

PMID- 7714067
TI  - Current status of combined androgen blockade: optimal therapy for advanced
      prostate cancer.
AB  - CAB represents the gold standard of treatment for patients with advanced prostate
      cancer. The treatment is well-tolerated with the only increased side effect being
      a 6% increase in diarrhea. Ninety-five percent of patients benefit, and those
      having minimal metastatic disease show a marked benefit. Since maximal androgen
      blockade seems to be of major benefit for patients with good performance status
      and minimal disease, its role needs to be investigated in patients with earlier
      stages of prostate cancer including stages B, C, and D1. Important trials are
      underway to address these provocative issues. Progress in the treatment of
      patients who relapse with metastatic prostate cancer after initial CAB will
      probably come to rely on the discovery and development of novel drugs or
      innovative drug delivery systems. Immunomodulatory drugs to enhance the body's
      natural defenses, monoclonal antibodies directed against prostate specific
      cellular antigens and tagged with radioisotopes or cytotoxic agents, and bone
      seeking radiopharmaceuticals may represent the breakthrough that is needed.
      Exciting advances in gene therapy may represent the ultimate chance for a cure.

PMID- 7714068
TI  - Endocrine therapy of prostate cancer: optimal form and timing.

PMID- 7714069
TI  - Is there a best endocrine treatment of prostate cancer?

PMID- 7714070
TI  - Prolonging survival in metastatic prostate cancer: the case for adrenal androgens
      -overview and summary of therapeutic controversies in prostatic cancer.

PMID- 7714071
TI  - Adrenal crisis in the newborn: details leading to the correct diagnosis.

PMID- 7714072
TI  - Severe cholestatic jaundice in uncomplicated hyperthyroidism treated with
      methimazole.

PMID- 7714073
TI  - Pyroglutamyl peptidase-II ("thyroliberinase") activity in human serum: influence
      of weight and thyroid status.
AB  - The tripeptide hormone, TRH, is metabolized by three enzymes, the most specific
      of which is pyroglutamyl peptide hydrolase-II (also termed thyroliberinase), a
      metalloenzyme present in serum and brain. Because pyroglutamyl peptidase-II
      activity in rat serum is regulated by thyroid hormone levels, we tested the
      hypothesis that this activity is similarly altered in humans. We studied serum
      pyroglutamyl peptidase-II activity in 6 patients with hyperthyroidism, 18
      patients with hypothyroidism, and 31 euthyroid, normal weight volunteers. Because
      TRH [or its metabolite cyclo(His-Pro)] is believed to be an important hormone
      regulating appetite and metabolism, we also evaluated pyroglutamyl peptidase-II
      activity in 27 euthyroid patients with obesity. Serum pyroglutamyl peptidase-II
      activity was elevated in patients with hypothyroidism (mean +/- SEM, 33.9 +/- 3.7
      nmol/mL.h) compared to that in euthyroid, normal weight volunteers (24.5 +/- 2.8
      nmol/mL.h; P < 0.05), but not that in patients with hyperthyroidism (28.3 +/- 4.1
      nmol/mL.h; P = NS). Euthyroid obese patients had the highest pyroglutamyl
      peptidase-II activity (43.6 +/- 2.8 nmol/mL.h; P < 0.0001 vs. normal weight
      volunteers). Pyroglutamyl peptidase-II activity was positively correlated with
      body mass index (r2 = 0.30; P < 0.0001). After correction for body mass index,
      there were no difference in pyroglutamyl peptidase-II activity in hypothyroid,
      hyperthyroid, and euthyroid individuals. We conclude that serum pyroglutamyl
      peptidase-II activity is regulated by, or regulates, body weight.

PMID- 7714074
TI  - Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide,
      before and during puberty.
AB  - The objective of this study was to verify the GH-releasing activity of a
      synthetic hexapeptide, hexarelin (HEX), before and during puberty. Ninety-six
      children (54 boys and 42 girls, aged 4.1-17.4 yr) were studied. Fifty-two of the
      children were prepubertal, and the other 44 were in pubertal stage II-IV. The GH
      response to 2 micrograms/kg HEX, iv (n = 56), was higher (P < 0.001) than that
      induced by 1 microgram/kg GHRH, iv (n = 33). The iv dose of 2.0 micrograms/kg HEX
      induced a greater GH increase (P < 0.02) than the 1.0 microgram/kg dose. The GH
      releasing effect of 10 mg HEX, orally, was greater (P < 0.03) than that of 1.0
      microgram/kg GHRH, iv (n = 7). The iv dose of 2 micrograms/kg HEX elicited an
      increase in GH levels that was higher in pubertal children than in prepubertal
      children (77.5 +/- 8.5 vs. 39.4 +/- 4.4 micrograms/L; P < 0.001). Before puberty,
      there was no sex-dependent difference in the GH response to HEX. It increased
      during puberty (P < 0.05 and P < 0.002 for boys and girls, respectively), when it
      was higher (P < 0.05) in girls than in boys. In contrast, GH responses to GHRH
      were not related to sex differences and/or puberty. In conclusion, HEX is a
      potent and reproducible stimulus of GH secretion in children. The effect of HEX
      increases in puberty, with girls showing a more marked GH response.

PMID- 7714075
TI  - Melatonin enhances the luteinizing hormone and follicle-stimulating hormone
      responses to gonadotropin-releasing hormone in the follicular, but not in the
      luteal, menstrual phase.
AB  - Exogenous melatonin enhances LH pulse amplitude and mean LH levels in women
      during the follicular, but not the luteal, menstrual phase. In this study we
      investigated whether an increased pituitary response to GnRH is involved in the
      stimulatory effect of melatonin. Eight normal cycling women were studied on 2
      consecutive days during the follicular stage (days 4-6), and eight were studied
      during the luteal phase (days 19-21) of the menstrual cycle. On 2 consecutive
      days, each women received, randomly and in a double blind fashion, placebo or 3
      mg melatonin (1 mg at 0800, 1000, and 1200 h), whereas the pituitary LH and FSH
      responses to GnRH were tested by the iv administration of three submaximal doses
      of GnRH (1 microgram at 0900 h, 5 micrograms at 1100 h, and 10 micrograms at 1300
      h). In the follicular phase, melatonin administration enhanced the LH and FSH
      responses to all three GnRH stimuli, whereas in the luteal phase, melatonin
      administration was ineffective. The present data indicate that an enhancing
      effect of melatonin on the LH and FSH responses to submaximal GnRH stimuli is
      evident in the follicular, but not the luteal, phase of the menstrual cycle and
      infer an endocrine window for the effect of melatonin on gonadotropin secretion.

PMID- 7714076
TI  - Biological mechanisms underlying the clinical effects of RU 486: modulation of
      cultured endometrial stromal cell plasminogen activator and plasminogen activator
      inhibitor expression.
AB  - The abortifacient and menstrual effects of the potent antiprogestin, RU 486, are
      associated with both endometrial hemorrhage and extracellular matrix (ECM)
      degradation. Such processes reflect reduced perivascular decidual cell hemostatic
      and increased ECM-degrading protease activity. Therefore, we assessed the effects
      of RU 486 administration on the expression of immunoreactive (ir) endometrial
      stromal cell urokinase-type (uPA) and tissue-type (tPA) plasminogen activator and
      their activities as well as levels of ir type 1 plasminogen activator inhibitor
      (PAI-1) using a well characterized in vitro model of decidualization. Thus,
      confluent stromal cell cultures were exposed to vehicle control, 10(-8) mol/L
      estradiol (E2), 10(-7)-10(-8) mol/L medroxyprogesterone acetate (MPA), E2 plus
      MPA, or 10(-6)-10(-7) mol/L RU 486 alone or in combination with MPA or E2 plus
      MPA for 3-4 days. Compared to the vehicle control, E2 and RU 486 used alone had
      no effect on levels of ir PAI-1, uPA, or tPA or on PA activity in the conditioned
      medium. In contrast, MPA and E2 plus MPA decreased ir uPA and tPA levels and
      their corresponding activities, whereas MPA increased, and E2 plus MPA further
      increased ir PAI-1 release. These effects of progestin were blocked by a log
      higher concentration of RU 486. Similar results were obtained for steady state
      PAI-1 messenger ribonucleic acid levels. To determine if RU 486 reversed
      progestin-inhibited stromal cell uPA and tPA release and progestin-enhanced PAI-1
      expression, confluent cultures were exposed to 10(-8) mol/L E2 plus 10(-7) mol/L
      MPA for 10 days, washed, and reexposed to E2 plus MPA, steroid-free medium, or RU
      486 for 3-5 or 9-11 days. Compared with cultures maintained in E2 plus MPA for 3
      5 days, withdrawal to a steroid-free medium failed to affect stromal cell ir PAI
      1, uPA, or tPA levels. In contrast, exposure to RU 486 for 3-5 days increased ir
      uPA and tPA levels 5- to 8-fold (P < 0.02) while reducing PAI-1 levels by 85% (P
      < 0.04). By 9-11 days of treatment, steroid withdrawal and RU 486 exerted similar
      effects on ir PAI-1, tPA, and uPA levels. Comparable results were obtained for
      PAI-1, uPA, and tPA steady state messenger ribonucleic acid levels. These
      findings indicate that RU 486 blocks and reverses progestin-inhibited PA
      expression, suggesting a mechanism for RU 486-induced endometrial hemorrhage and
      ECM dissolution.

PMID- 7714077
TI  - Immunohistochemical localization of heat shock proteins HSP70 and HSP90 in the
      human endometrium: correlation with sex steroid receptors and Ki-67 antigen
      expression.
AB  - Heat shock proteins of 72 kDa and 90 kDa (HSP70, HSP90) have been suggested to be
      involved in the functional modulation of sex steroid receptors. We examined the
      immunohistochemical localization of HSP70 and HSP90 in both the functionalis and
      basalis layers of normal human endometrium during various phases of the menstrual
      cycle. Topological correlation with localization of estrogen receptors (ER),
      progesterone receptors (PR), and proliferation-related Ki-67 antigen was also
      analyzed. HSP70 was expressed in glandular cells of the basalis but not in the
      cells of the functionalis during the proliferative phase. In the secretory phase,
      however, glandular cells of both the basalis and functionalis markedly expressed
      HSP70. Endometrial stromal cells at the basal layer were positive for HSP70,
      whereas those cells in the functional layer were negative for HSP70 throughout
      the menstrual cycle. The topological expression of HSP70 in glandular and stromal
      cells of the basalis was inversely related to Ki-67 localization. Overexpression
      of HSP70 in the secretory glands was associated with down-regulation of ER and
      PR. These findings suggest that HSP70 expression is related to either hormonal
      regulation of cell proliferation and/or down-regulation of sex steroid receptors.
      HSP90 was strongly expressed in both glandular and stromal cells during the
      proliferative phase of the menstrual cycle; in the secretory phase, HSP90
      expression was weak in both types of the cells. However, no topological
      difference in HSP90 expression between the basalis and the functionalis was
      observed.

PMID- 7714078
TI  - Growth hormone treatment does not alter biliary lipid metabolism in healthy adult
      men.
AB  - GH is important for the hepatic low density lipoprotein (LDL) receptor induction
      that occurs after estrogen treatment. GH treatment increases liver LDL receptors
      and lowers plasma LDL cholesterol in man. Estrogen treatment enhances biliary
      secretion of cholesterol, resulting in supersaturation of bile and an increased
      risk of gallstone formation. The present study was undertaken to investigate
      whether GH treatment also influences biliary lipid metabolism in humans. Twelve
      healthy male volunteers (mean age, 31 +/- 1 yr) were studied before and during
      the third week of treatment with recombinant human GH (0.1 IU/kg.day). Plasma
      lipids, bile acid kinetics, and biliary lipid composition were monitored. Plasma
      total and LDL cholesterol levels were reduced by 10% in response to therapy.
      However, no significant changes were observed in the biliary lipid composition or
      cholesterol saturation of gallbladder bile. Furthermore, there were no changes in
      chenodeoxycholic acid or cholic acid kinetics. The reduction of plasma LDL
      cholesterol in response to GH treatment in healthy adult men is not associated
      with detectable changes in biliary lipid metabolism. Thus, in contrast to
      estrogen, GH therapy of adults probably does not result in an increased risk of
      cholesterol gallstone development.

PMID- 7714079
TI  - Body weight versus body fat distribution, adiposity, and frame size as predictors
      of bone density.
AB  - Weight is strongly associated with bone mineral density (BMD), but the mechanism
      of this effect is not well understood. Weight, height, hip-waist ratio, elbow
      breadth, adiposity, and BMD were measured in 6705 older women participating in
      the Study of Osteoporotic Fractures. Adiposity was measured by bioelectric
      impedance and BMD by single-photon (proximal and distal radius and calcaneus) and
      dual-energy x-ray absorptiometry (lumbar spine and proximal femur). Age-adjusted
      associations between weight and BMD were robust at all sites (R2 = 5.9-20.4%),
      but the addition of other anthropometric variables to the model only marginally
      improved the association. Adiposity explained a substantial fraction of the
      effect of weight on BMD, particularly at weight-bearing sites (36-62%). On the
      other hand, weight explained virtually all the variability of adiposity on BMD at
      weight-bearing sites (81-100%). At the radial measurement sites, adiposity had
      more substantial independent contributions. Weight did not seem to influence the
      relationship between BMD and age. In sum, at weight bearing-sites, the
      preponderance of the effect of weight on BMD is a direct result of mass effects
      rather than adiposity, whereas at non-weight-bearing sites, adiposity exerts more
      important effects, potentially mediated by metabolic factors.

PMID- 7714080
TI  - Bioactivity of thyrotropin (TSH) in patients with central hypothyroidism:
      comparison between in vivo 3,5,3'-triiodothyronine response to TSH and in vitro
      bioactivity of TSH.
AB  - To investigate the cause(s) of central hypothyroidism with normal or elevated TSH
      concentrations, we evaluated the bioactivity of serum TSH as well as pituitary
      and thyroid function. Seven hypothyroid patients had documented deficiencies of
      anterior pituitary hormones other than TSH. Basal TSH concentrations ranged from
      2.2-14.8 microU/mL. Six patients had low T4 and free T4 concentrations; the
      remaining patient had a low free T4 and a low normal T4 level with an elevated
      TSH concentration of 14.4 microU/mL. The mean increment in TSH 30, 60, and 90 min
      after TRH administration (mean delta TSH) in these patients was 13.5 +/- 9.1
      microU/mL (mean +/- SD), which was not significantly different from the value in
      controls (9.2 +/- 3.5 microU/mL). However, the ratio of the T3 increment at 120
      min (delta T3) to mean delta TSH (delta T3/mean delta TSH) in patients was 53.9
      +/- 29.3 ng/microU, significantly lower than the control value of 239.5 +/- 97.5
      ng/microU (P < 0.01), suggesting that the thyroid response to endogenous TSH was
      blunted. The serum T4 concentration correlated with the mean delta TSH in these
      patients (r = 0.78; P < 0.05), suggesting that hypothyroidism is dependent on
      conserved pituitary function. The mean bioactivity to immunoreactivity ratio of
      basal TSH in patients was 0.97 +/- 0.27 and was not significantly different from
      the normal value of 1.05 +/- 0.22. One of the two patients with high basal TSH (>
      10 microU/mL) had a ratio of 0.59, which is just below the mean +/- SD of normal
      subjects (0.61), suggesting that most patients had normal TSH bioactivity in
      vitro. Our findings suggest that in vivo bioactivity of TSH is decreased because
      of a pituitary disorder, but in vitro bioactivity of TSH is variable in patients
      with central hypothyroidism.

PMID- 7714081
TI  - Retinoic acid induces intercellular adhesion molecule-1 hyperexpression in human
      thyroid carcinoma cell lines.
AB  - The expression of intercellular adhesion molecule-1 (ICAM-1) in tumoral tissues
      may promote their interaction with the immune system and cytotoxic effect on
      tumoral cells. This observation led to the investigation of ICAM-1 expression and
      modulation in different tumoral cell systems in vitro. Recently, retinoic acid
      responsive elements have been found in the 5'-regulatory region of the human ICAM
      1 gene. In the present study, we investigated, by flow cytometry, the effect of
      retinoic acid on the surface expression of ICAM-1 in human thyroid carcinoma cell
      lines. Two papillary (NPA and TPC-1), one follicular (WRO), one anaplastic (ARO)
      and one immortalized fetal (TAD-2) cell line have been studied. All of them
      produced constitutively ICAM-1; its surface expression and specific messenger
      ribonucleic acid (mRNA) levels were increased significantly by retinoic acid in
      all except the WRO cell line. ICAM-1 hyperexpression by retinoic acid was time
      dependent, reversible, and dependent on mRNA and protein synthesis. Furthermore,
      cytokines, such as interferon-gamma and tumor necrosis factor-alpha, both
      individually and, to a greater extent, in combination with retinoic acid,
      increased ICAM-1 surface expression and its mRNA levels. In conclusion, retinoic
      acid is able to induce ICAM-1 up-regulation via mRNA accumulation in human
      thyroid carcinoma cell lines.

PMID- 7714082
TI  - Physiological concentrations of thyrotropin increase cytosolic calcium levels in
      primary cultures of human thyroid cells.
AB  - The activity of TSH, the main regulator of growth and differentiation in the
      thyroid, has been mainly related to the activation of the adenylyl cyclase
      cascade. TSH also activates phospholipase-C and -A2; these effects, however, have
      been reported to require concentrations of the hormone up to 1000-fold higher
      than those effective on adenylyl cyclase, suggesting that the main physiological
      mechanism involved in the action of TSH is the activation of this enzyme. Using
      primary cultures of human thyroids, we here show that physiological
      concentrations of TSH (0.01-10 mU/L) are also able to increase intracellular Ca2+
      levels. Cells were loaded with the fluorescent Ca2+ probe fura-2 and analyzed by
      single cell Ca2+ recording. The basal Ca2+ level was 105 +/- 30 nmol/L, and
      physiological concentrations of TSH increased it by 2- to 7-fold. The Ca2+
      increase was transient and lasted up to 10 min. It is also shown that the TSH
      dependent Ca2+ increase involves both the activation of phospholipase-C and the
      entry of extracellular Ca2+. TSH (100-10000 mU/L) increased cAMP levels by up to
      20-fold in parallel experiments performed on the same cell preparations. These
      data demonstrate that physiological concentrations of TSH are able to increase
      cytosolic Ca2+ levels, indicating that this second messenger might directly
      mediate the action of this hormone in the thyroid.

PMID- 7714084
TI  - Effect of oral isotretinoin treatment on skin androgen receptor levels in male
      acneic patients.
AB  - An oral daily dose (mean +/- SD, 0.75 +/- 0.05 mg/kg) of isotretinoin was
      administered for 3 months to six male patients with acne (scores of 4 and 5
      according to Rosenfield). The therapy resulted in complete resolution of acne in
      four patients and improved acne significantly (score 1) in two patients. In
      accordance with recent findings, no change in serum testosterone and significant
      decreases in 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol
      glucosiduronate, and androsterone glucosiduronate levels were observed after
      treatment. Androgen receptor status was investigated in back skin biopsies
      obtained in acne areas before and after 3 months of isotretinoin treatment. The
      treatment did not modify the binding affinity constant of skin androgen receptor
      (0.44 vs. 0.32 nmol/L), but it did induce a 2.6-fold decrease in its binding
      capacity constant (62 vs. 24 fmol/mg cytosolic protein), as assessed by Scatchard
      plot and confirmed immunologically by Western blot analysis. These data clearly
      showed that skin androgen receptor was sensitive to oral isotretinoin
      administration in acneic patients. The decrease in skin androgen receptor levels
      (this study) and the recently reported suppression of skin 5 alpha
      dihydrotestosterone production by isotretinoin treatment appeared consistent with
      the involvement of androgen receptor and 5 alpha-dihydrotestosterone in the
      pathogenesis of acne. Indeed, sebum production is under androgen control, and an
      abnormal response of the pilosebaceous unit to androgens appears to be implicated
      in the pathogenesis of acne. These observations were consistent with the absence
      of sebum in complete androgen-insensitive patients and normal sebum production in
      male pseudohermaphrodites.

PMID- 7714083
TI  - Antithyroid effects in vivo and in vitro of vitexin: a C-glucosylflavone in
      millet.
AB  - Millet diets rich in C-glycosylflavones (C-GF) are goitrogenic, and its three
      most abundant C-GF inhibit in vitro thyroid peroxidase, suggesting that these
      compounds are the goitrogens in millet. However, proof of a cause and effect
      relationship between C-GF and goitrogenesis requires a demonstration of in vivo
      antithyroid activity by the purified isolated compounds. Vitexin, one of the
      three major C-GF in millet, was used to test this hypothesis. Twenty-four female
      Wistar rats, divided into groups of six rats each and fed Purina iodine-rich diet
      (12 micrograms I-/day.rat), were administered acutely by gastrointestinal tube
      goitrogen-free water (controls), methimazole (0.5 mumol), and vitexin (20 and 80
      mumol). 125I (1 microCi) was injected ip 1 h later, and the rats were killed 2 h
      after the injection. The thyroid glands were removed and analyzed for their
      content of total 125I and 125I-labeled compounds. Rats given vitexin, in contrast
      to those receiving methimazole, did not show suppressed thyroid 125I uptake.
      However, significant inhibition of the coupling mechanism (high 125I-labeled
      monoiodotyrosine plus diiodotyrosine/125T3 plus T4 ratio and low 125T3 and T4
      concentrations) did occur with the highest dose of vitexin. These results provide
      direct evidence in vivo of C-GF antithyroid activity, strongly supporting the
      concept that C-GF are the goitrogens in millet.

PMID- 7714085
TI  - A new constitutively activating point mutation in the luteinizing
      hormone/choriogonadotropin receptor gene in cases of male-limited precocious
      puberty.
AB  - A single point mutation that encodes an aspartic acid (Asp578) to glycine
      substitution in the LH/CG receptor (LH/CGR) gene, D578G, was recently found in
      American patients with familial male-limited precocious puberty and in a Japanese
      patient with a sporadic form of the disorder. Transfection of the mutant,
      compared to the wild-type, LH/CGR complementary DNA into COS-7 cells results in
      higher basal cAMP production, but a normal agonist-induced response; the mutation
      is, therefore, proposed to constitutively activate Leydig cells and elevate serum
      testosterone, despite low levels of gonadotropin. In the current study we
      examined two additional Japanese patients with male-limited precocious puberty
      without a family history of the disease. We describe a heterozygous cytosine (C)
      to thymine (T) transition at nucleotide 1715 in both; the mutation encodes an
      alanine to valine substitution in codon 572 of transmembrane helix 6, A572V.
      Transfected into COS-7 cells, the A572V mutant exhibited the same constitutively
      high basal cAMP levels and normal agonist-induced cAMP response as the D578G
      mutant. We conclude that the constitutively higher cAMP levels caused by the
      A572V mutation led to Leydig cell activation and male-limited precocious puberty,
      as in the previously described D578G mutation. As the mother of one of the two
      patients had the same heterozygous mutation, this patient represents the first
      recognized case of inherited male-limited precocious puberty in the Japanese
      population. The previously described D578G mutant did not increase basal or
      agonist-induced inositol phosphate production in transfected COS-7 cells, or the
      number of LH/CGRs or their affinity for LH/CG. In contrast, transfection of the
      A572V mutation in COS-7 cells exhibited significantly higher inositol phosphate
      levels basally and at 10(-11) mol/L hCG, but significantly lower inositol
      phosphate levels at 10(-7) mol/L hCG. These data suggest that the A572V mutation
      of the LH/CGR may have effects on the guanine nucleotide binding protein which
      activates phospholipase C (Gq) coupling and phospholipase-C activation in
      addition to its effects on Gs coupling and activation of adenylyl cyclase. A572V
      transfected cells also exhibited a higher affinity, despite an apparent decrease
      in the number of binding sites, for [125I]hCG, compared to transfectants with the
      wild-type LH/CGR. We hypothesize that these differences between the A572V and
      D578G mutations reflect a greater impact of the A572V mutation on receptor
      conformation.

PMID- 7714086
TI  - Oral contraceptive pills, gonadotropin-releasing hormone agonists, or use in
      combination for treatment of hirsutism: a clinical research center study.
AB  - The effectiveness of oral contraceptive pills (OCPs), GnRH agonist (GnRH-a), and
      a combination of OCPs and GnRH-a in the treatment of hirsute women was compared
      and the impact of these treatments on hormonal and Ca metabolism was
      investigated. Thirty-three women were prospectively enrolled and randomized into
      three treatment groups (11 in each group). The serum levels of LH, estradiol,
      testosterone, free testosterone, androstenedione, and 17-hydroxyprogesterone
      declined in all 3 treatment groups, whereas the inclusion of GnRH-a treatment
      tended to promote a more rapid decrease in these hormone levels. Total
      cholesterol, low density lipoprotein, and high density lipoprotein levels
      remained unchanged. The assessment of hirsutism by the Ferriman-Gallwey score
      revealed a similar 25% reduction in score by all three treatment groups by 6
      months. In addition, no difference was detected between groups with respect to
      hair diameters and the vellus index. Clinical assessment of hirsutism at 3 months
      by the patients revealed that the GnRH-a and the OCPs-plus-GnRH-a groups had
      better responses than the group on OCPs alone, but by 6 months all three groups
      were similar. The symptoms of hot flashes and vaginal dryness were greatest in
      subjects treated with GnRH-a alone. Serum Ca, phosphorus, alkaline phosphatase,
      osteocalcin, and 2-h fasting and 24-h urinary Ca excretion levels all increased
      significantly in subjects treated with the GnRH-a alone, whereas a decrement or
      no changes occurred for these measurement in the other two groups. The estimated
      Ca balance was unchanged in the OCPs and the OCPs-plus-GnRH-a groups but declined
      by 90 mg/day from baseline in the GnRH-a-treated women (p < or = 0.001). Bone
      density significantly decreased in the lumber spine in women treated with GnRH-a
      alone, with a less marked decline in the femoral neck. In contrast, women
      receiving OCPs plus GnRH had increased bone density in the lumbar spine. It is
      concluded that: 1) clinical measures of hirsutism are not different after 6
      months of treatment with OCPs alone, GnRH-a alone, or a combination of the two;
      2) the decline in gonadotropins and steroid hormones and improvement in clinical
      response were more rapid and pronounced when GnRH-a treatment was added to OCP
      administration; and 3) the negative impact of GnRH-a alone on Ca balance and bone
      loss limits its usefulness as a single agent for long-term therapy of hirsutism.

PMID- 7714087
TI  - Proposed cause of marked vasopressin resistance in a female with an X-linked
      recessive V2 receptor abnormality.
AB  - Almost all cases of congenital nephrogenic diabetes insipidus (NDI) are
      transmitted in an X-linked recessive manner by an asymptomatic carrier female to
      her affected son. Severe symptomatic NDI has not previously been reported in a
      female with X-linked recessive NDI. Each of the three members of this family has
      an abnormal V2 receptor gene, which results in truncation of the V2 receptor
      beginning at arginine-337. This prematurely terminates the receptor at the
      carboxy-terminal tail and very likely disrupts receptor function. The son has an
      abnormal V2 receptor gene on his X-chromosome, whereas the mother and daughter
      have one normal and one abnormal gene for the V2 receptor. The infusion of
      desmopressin into the mother and son reveals a total lack of antidiuretic
      response, whereas the daughter increases urinary osmolality normally. The plasma
      factor VIII concentration after the infusion of desmopressin in the son does not
      rise, whereas the mother and daughter have half of the normal factor VIII
      response, similar to asymptomatic female carriers of NDI. These responses to
      desmopressin in daughter and son are those of a typical carrier female and male
      affected with NDI. In contrast, the mother acts as an NDI patient when the urine
      concentration is measured, but acts as a carrier in terms of the factor VIII
      response to desmopressin. We postulate that the renal tubular cells of the mother
      demonstrate extreme lyonization of X-chromosome inactivation, whereas in the
      tissue that subserves the hematological response to desmopressin, X-chromosome
      inactivation followed a more typically random distribution.

PMID- 7714088
TI  - Short-term fasting affects luteinizing hormone secretory dynamics but not
      reproductive function in normal-weight sedentary women.
AB  - Acute food withdrawal reversibly inhibits the hypothalamic-pituitary-gonadal axis
      in men and in rhesus monkeys, and it produces defects in LH pulsatility in normal
      weight women. However, the clinical effect of short-term nutritional deprivation
      on the reproductive axis of normally cycling women has not been evaluated. Thus
      we studied the effect of a 3-day fast during the midfollicular phase on menstrual
      cycle length, gonadotropin secretory patterns, follicular development, and
      ovulation. After a baseline ovulatory cycle, 12 women within 15% of ideal body
      weight were randomized to be fed (n = 7) or fasted (n = 10) on cycle days 7 to 9.
      Five of the women repeated the study and received the alternate diet. Endocrine
      and metabolic parameters of fasting and reproductive physiology were measured on
      cycle days 6 to 12. Fasted physiology was demonstrated by characteristic
      alterations in growth hormone, insulin-like growth factor I, TSH, and T3 levels.
      During fed cycles, the number of LH pulses remained constant on cycle days 6, 9
      and 11, whereas mean LH levels, LH area under the curve, and LH pulse amplitude
      increased significantly over this time (all P < 0.05). In contrast, fasted cycles
      were marked by a significant decrease in the number of LH pulses on the last day
      of the fast (cycle day 9, P < 0.05) and by a lack of increase over time of mean
      LH values, LH area under the curve, and LH pulse amplitude. Follicle development,
      as assessed by daily ultrasound examination and estradiol measurements, was
      similar in all cycles and was followed by ovulation in all women; follicular and
      luteal phase lengths of fasted and fed cycles were similar. We conclude that the
      alterations in LH secretory dynamics that occur during a 3-day fast are not
      sufficient to perturb follicle development and cycle lengths in normal-weight
      sedentary women. The resilience of the reproductive axis in these healthy women
      contrasts with the sensitivity of the hypothalamic-pituitary-gonadal axis to
      acute nutritional withdrawal in men and in monkeys. We speculate that differences
      in the set point for sensing fuel availability or in the status of energy balance
      before the initiation of food deprivation may account for these species-specific
      and sex-specific variabilities.

PMID- 7714089
TI  - Influence of age, sex, and insulin on osteoblast function: osteoblast dysfunction
      in diabetes mellitus.
AB  - The osteoblast function was evaluated in normal and diabetic children and adults
      by measurements of the serum concentration of the carboxy-terminal extension
      peptide of procollagen (PICP), total and skeletal alkaline phosphatase (ALP), and
      osteocalcin. Moreover, the osteoblast-stimulating growth factor, insulin-like
      growth factor I (IGF-I), was measured in the same samples. In normal children (n
      = 420; age, 5-20 yr), a marked pubertal increase of serum IGF-I (peak values at
      age 14-16 yr in both sexes), osteocalcin, and total and skeletal ALP (peak values
      earlier in girls than in boys) and a small increase in PICP were observed. All
      osteoblast markers and IGF-I were markedly lower in normal adults (n = 229; age,
      21-69 yr) than in children. All osteoblast parameters showed a high degree of
      correlation (P < 0.001) with each other. In adolescents (n = 104) treated for
      insulin-dependent diabetes mellitus (IDDM), serum IGF-I (-19%), osteocalcin (
      28%), and skeletal ALP (-28%) were markedly decreased, whereas total ALP was
      significantly increased (29%), and serum PICP remained normal. In adult IDDM (n =
      125), both serum IGF-I (-41%) and osteocalcin (-24%) were decreased, but skeletal
      ALP and PICP remained normal. A similar abnormality in serum IGF-I and
      osteocalcin was observed in white (n = 61) and Pima Indian (n = 16) non-IDDM
      patients. The concentration of skeletal ALP was highly significantly correlated
      (r > or = 0.9) with total ALP in both normal and diabetic subjects, but the slope
      of the regression was significantly different, indicating the presence of other,
      probably intestinal, ALP in all types of diabetes. In conclusion, the osteoblast
      function is significantly decreased in diabetic patients, which can best be
      characterized as a maturation defect, since the early osteoblast marker, PICP,
      remained normal in all types of diabetes, whereas a later marker, skeletal ALP,
      is frankly abnormal only in diabetic children. The most mature osteoblast marker,
      osteocalcin, is decreased in all types of diabetes irrespective of age.

PMID- 7714090
TI  - Prevalence of nonthyroid specific autoantibodies in autoimmune thyroid diseases.
AB  - To clarify the involvement of polyclonal activation of autoimmune reaction in
      organ-specific autoimmune diseases, we investigated the prevalence of nonthyroid
      specific autoantibodies in 50 patients with autoimmune thyroid diseases (22
      patients with Graves' disease and 28 with Hashimoto's disease) and in 50 age- and
      sex-matched controls. None of the 100 subjects had any clinical manifestations or
      laboratory data indicating any other immunological, infectious, hepatic, or
      malignant diseases. The prevalence of positive antibodies to nucleus, smooth
      muscle, and single-stranded DNA in the patients (26%, 36%, and 34%, respectively)
      was higher than that in the control group (8%, 4%, and 4%, respectively),
      although neither group was positive for autoantibodies against double-stranded
      DNA, extractable nuclear antigen, SS-A, SS-B, mitochondria, or rheumatoid factor.
      Furthermore, 66% of the patients had at least one autoantibody to nucleus, smooth
      muscle, or single-stranded DNA. In conclusion, patients with autoimmune thyroid
      diseases show high prevalence of autoantibody against not only thyroid-specific,
      but also nonthyroid-specific antigens. These results are consistent with the
      concept that immune reaction of patients with organ-specific autoimmune diseases
      may be polyclonally accelerated to the production of antibodies against both
      organ and nonorgan specific autoantigens.

PMID- 7714091
TI  - Insulin resistance associated with decreased levels of insulin-receptor messenger
      ribonucleic acid: evidence of a de novo mutation in the maternal allele.
AB  - Mutations in the insulin receptor gene may lead to insulin resistance and
      diabetes mellitus in some patients. We have studied an insulin-resistant patient
      with leprechaunism. Insulin binding to the patient's fibroblasts was markedly
      decreased. Determination of the nucleotide sequence of the patient's insulin
      receptor gene revealed heterozygosity for a 2-basepair deletion in exon 15. If
      the premessenger ribonucleic acid (pre-mRNA) is spliced normally, it causes a
      replacement of codon 970 in the beta-subunit with a premature chain termination
      codon, thereby deleting most of the intracellular domain of the receptor. The
      mRNA transcribed from the allele with a 2-base-pair deletion is likely to be
      unstable because mRNA transcripts from this allele could not be detected by
      complementary DNA sequencing. Northern blot analysis showed that the patient's
      insulin receptor mRNA was decreased by 90% compared with that of a control
      subject, thus suggesting that the patient is a compound heterozygote for two
      mutations that decrease levels of insulin receptor mRNA. This deletion mutation
      in exon 15 seems to be a de novo mutation, because it was not detected in either
      parent. Investigation of the inheritance of a silent sequence polymorphism in
      exon 17 provided that the deletion occurred in the maternal allele. Furthermore,
      linkage analysis suggests that the second mutation is derived from the patient's
      father, although we could not directly identify it by sequencing the coding
      region of the insulin receptor gene. Therefore, it is possible that this mutation
      is present in a regulatory domain of the insulin receptor gene, acting in cis
      dominant fashion to reduce the levels of insulin receptor mRNA. Analyses of the
      hypervariable region in the myoglobin and pMCT118 loci were consistent with the
      assumption that the father and mother studied here are indeed the biological
      parents of the diseased patient. We hereby conclude that the patient is a
      compound heterozygote for two mutant alleles, both of which are responsible for
      the reduced levels of insulin receptor mRNA and insulin binding.

PMID- 7714092
TI  - Native gel electrophoresis and isoelectric focusing of a 64-kilodalton eye muscle
      protein shows that it is an important target for serum autoantibodies in patients
      with thyroid-associated ophthalmopathy and not expressed in other skeletal
      muscle.
AB  - Although sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      Western blotting are widely used to detect serum antibodies in patients with
      autoimmune disorders, this procedure unfolds and denatures proteins and may alter
      antibody-binding sites. We have used a gentle protocol for the preparation and
      purification of a 64-kilodalton (kDa) eye muscle (EM) membrane antigen associated
      with thyroid-associated ophthalmopathy (TAO) for use as antigen in
      immunoblotting. Pig EM membrane proteins were prepared from crude homogenates by
      high speed centrifugation and solubilized by hand homogenization. These native
      membrane proteins (NMprot) were then electrophoresed on an 8.5% polyacrylamide
      gel in the absence of SDS, reducing agents, or urea, and proteins from individual
      bands were eluted, applied to standard SDS-PAGE, and immunoblotted with selected
      TAO patient sera. A prominent 64-kDa protein, present in most of the bands, was
      recognized by autoantibodies in sera from 35% of the patients with TAO and 47% of
      those with Graves' hyperthyroidism without evident ophthalmopathy, but in only 4%
      of normal subjects. To further purify the 64-kDa protein and increase the
      sensitivity of immunoblotting, NMprot were separated by isoelectric focusing
      (IEF) in the absence of SDS, reducing agent, and urea. The 64-kDa protein
      appeared mainly in IEF fraction 7 and had an isoelectric point of 6.1-6.2.
      Similar results were found for a human EM protein of 64 kDa. Sera from groups of
      patients and normal subjects were tested in immunoblotting against a pig EM 64
      kDa protein prepared from NMprot and purified in IEF. Tests were positive in 67%
      of patients with TAO, in 37.5% of those with Graves' hyperthyroidism without eye
      disease, in 11% of patients with Hashimoto's thyroiditis without eye disease, and
      in 9% of normal subjects. The 64-kDa protein was not found in other skeletal
      muscle. The demonstration that a native 64-kDa protein that is specifically
      targeted by autoantibodies in the serum of patients with TAO is expressed in EM,
      but not other skeletal muscle, greatly enhances its possible significance in the
      pathogenesis of this eye disorder.

PMID- 7714093
TI  - Angiotensin-II stimulates estradiol secretion from human placental explants
      through AT1 receptor activation.
AB  - A complete renin-angiotensin system has been shown to be present in human
      placenta, but its physiological role is poorly known. To investigate the
      implication of this system in the regulation of steroid hormone secretion, we
      studied the effect of angiotensin-II on the release of estradiol and progesterone
      from human placental explants. Our experiments showed that angiotensin-II
      stimulated estradiol secretion from term placental explants in a dose- and time
      dependent fashion, although progesterone release was unaffected. Estradiol
      release induced by angiotensin-II (0.2 mumol/L) was blocked by angiotensin AT1
      receptor antagonist losartan in a dose-dependent manner, suggesting the
      involvement of the AT1 receptor subtype in the process. On the contrary, the
      angiotensin AT2 receptor antagonist PD123319 (1 mumol/L) or the angiotensin AT2
      receptor agonist CGP42112A (1 mumol/L) had no effect. Analysis of the amount of
      steroid hormones in the placental tissues incubated for 12 h showed that
      angiotensin-II increased estradiol production by 34% compared with the
      unstimulated explants, whereas the total levels of the estrogen precursor
      androstenedione and testosterone were decreased by 30-45% in the presence of the
      peptide, suggesting a stimulatory effect on the aromatization step. This
      hypothesis was reinforced by the absence of effect of angiotensin-II on both
      estradiol and testosterone concentrations in the placental explants pretreated
      with the aromatase inhibitor 4-hydroxyandrostenedione (25 mumol/L). Progesterone
      synthesis was not affected by angiotensin-II. The present study indicates that
      angiotensin-II induces the secretion of estradiol from human placenta through the
      angiotensin AT1 receptor subtype activation, and this effect seems to be linked
      to the stimulation of local androgen aromatization.

PMID- 7714094
TI  - Dissociation of plasma adrenocorticotropin and cortisol levels in critically ill
      patients: possible role of endothelin and atrial natriuretic hormone.
AB  - The regulatory mechanisms of the hypothalamo-pituitary-adrenal system were
      studied in critically ill, intensive care unit patients. Serial measurements of
      immunoreactive ACTH-(1-39) (ACTHi), cortisol, endothelin-1 (ETi), and atrial
      natriuretic hormone (ANHi) were performed in blood samples of 18 patients with
      clinically defined sepsis, 12 critically ill patients after multiple trauma, and
      15 hospitalized matched control subjects without acute illness for 8 consecutive
      days after admission. On admission, plasma levels of cortisol and ACTHi were
      significantly elevated in patients with sepsis (1.32 +/- 0.21 mumol/L and 130.0
      +/- 38.2 pmol/L, mean +/- SD) and with multiple trauma (1.23 +/- 0.28 mumol/L and
      123.7 +/- 41.3 pmol/L) compared to those in the control subjects (0.37 +/- 0.08
      mumol/L and 15.6 +/- 5.8 pmol/L, respectively). The plasma cortisol levels of
      critically ill patients remained high (> 0.8 mumol/L) during the whole
      observation period. In contrast, plasma ACTHi levels decreased between days 3-5,
      reaching significantly lower levels on day 5 compared to those in the control
      group and remained below 5.0 pmol/L during the rest of the observation period.
      Plasma levels of ETi and ANHi were significantly elevated during the whole period
      in both patient groups (ETi, > 10 ng/L; ANHi, > 250 ng/L) compared to those in
      control subjects (< 5 and < 50 ng/L, respectively). The high plasma concentration
      of ETi observed in our patients may stimulate the steroid secretion of the
      adrenal cortex directly or potentiate the adrenal effect of ACTH. On the other
      hand, the increased concentration of ANHi found in critically ill patients
      together with the increased plasma cortisol level may explain the inhibition of
      ACTH secretion. Accordingly, we speculate that the high ET level exerts a
      positive drive on the adrenocortical level, that the high ANH level has an
      inhibitory effect on the hypothalamo-pituitary level, and that both mechanisms
      play a role in regulation of the hypothalamo-pituitary-adrenal axis during
      critical illness.

PMID- 7714095
TI  - Low-dose adrenocorticotropin test reveals impaired adrenal function in patients
      taking inhaled corticosteroids.
AB  - The aim of the present study was to examine the use of low-dose ACTH-(1-24)
      stimulation for assessment of adrenal function and the detection of mild adrenal
      insufficiency. The criteria for normal response to ACTH-(1-24) are a peak
      cortisol level of more than 500 nmol/L (18.1 micrograms/dL) and an increment of
      the cortisol level above the basal one of more than 200 nmol/L (7.2
      micrograms/dL). These criteria were satisfied by 32 of 33 healthy children and
      adults subjected to an ACTH-(1-24) dose 500 times lower (0.5 micrograms/1.73 m2)
      than the dose of 250 micrograms in the standard test. At 20 min, the peak
      cortisol level was the same in the low-dose test [(621 +/- 28 nmol/L) (22.5 +/-
      1.0 microgram/dL)] as in the standard ACTH test [(654 +/- 31 nmol/L) (23.7 +/-
      1.1 microgram/dL)]. Of 46 asthmatic patients who had been treated with inhaled
      beclomethasone dipropionate (482 +/- 42 micrograms/m2 daily; n = 32) or
      budesonide (507 +/- 62 micrograms/m2 daily; n = 14) for over 6 months, 16 (35%)
      failed to reach a cortisol peak of more than 500 nmol/L (18.1 micrograms/dL)
      following stimulation with 0.5 micrograms ACTH-(1-24)/1.73 m2. Of these, 11 (24%)
      showed a cortisol increment of less than 200 nmol/L (7.2 micrograms/dL). These 16
      patients, showing insufficient response to low-dose ACTH-(1-24), also had a
      significantly lower (P < 0.01) mean 24-h urinary free cortisol excretion [(71 +/-
      10 nmol/m2.24 h) (25.7 +/- 3.6 micrograms/m2.24 h)] than patients who responded
      normally [(118 +/- 11 nmol/m2.24 h) (42.8 +/- 4.0 micrograms/m2.24 h).
      Nonetheless, all but one of the poor responders to a 0.5 microgram ACTH showed
      normal stimulation with the standard 250 micrograms ACTH test. Therefore, it
      appears that a low-dose ACTH test is capable of revealing mild adrenal
      insufficiency, which is not detected by the standard high-dose ACTH test.

PMID- 7714096
TI  - Screening for growth hormone (GH) gene splice-site mutations in sporadic cases
      with severe isolated GH deficiency using ectopic transcript analysis.
AB  - We screened 10 children with sporadic severe isolated GH deficiency (IGHD) for GH
      1 gene splice site mutations using ectopic transcript analysis. None had a
      history of birth trauma, congenital defects, thyroid disorders, or PRL
      deficiency. The mean age of these patients at diagnosis was 3.5 yr; the mean
      height at diagnosis was -4.0 SD score. GH-1 gene deletion was excluded in all
      cases. Ribonucleic acid (RNA) from lymphocytes was reverse transcribed and
      amplified by nested polymerase chain reaction, using two primer pairs with
      annealing sites within exons 2 and 5 of the GH-1 gene. The main polymerase chain
      reaction fragment obtained was 460 basepairs and proved to be the amplification
      of the GH-1 transcript. We also found three shorter fragments which were
      alternatively spliced GH-1 transcripts, including a variant devoid of the first
      45 basepairs of exon 3, a second lacking the whole exon 3, and a third one, not
      previously described, lacking both exon 3 and exon 4. We found the same pattern
      of alternative splicing in RNA from GH-producing pituitary tumor tissue, which
      served as a positive control. In 1 of 10 patients, a pathologically shortened
      main fragment lacking exon 3 was detected. As proved by sequencing genomic DNA,
      this was the result of a heterozygous splice site mutation, with transversion
      from G to C of the first base of the donor splice site of intron III generating a
      new DdeI recognition site. The other allele had no mutation. DdeI digestion
      enabled us to rule out the defect in the parents' DNA. Thus, the mutation was de
      novo. As the patient with the mutation displayed the most severe and earliest
      growth retardation in the study group and had virtually no GH in serum, it must
      be assumed that the heterozygous genetic defect resulted in a dominant negative
      effect. The reason for this is still unclear. Recently, within a family that
      exhibited the autosomal dominant phenotype of IGHD (IGHD-II), a heterozygous
      point mutation was located 5 bases down-stream from that we describe here. A
      similar effect on splicing was observed. In conclusion, analysis of ectopic GH-1
      transcripts enabled us to detect 1) a new alternatively spliced GH-1 messenger
      RNA variant lacking exons 3 and 4, and 2) 1 of 10 sporadic cases of severe
      idiopathic IGHD due to a heterozygous de novo splice site mutation in the GH-1
      gene that changes G to C in the first base of intron III.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7714097
TI  - Molecular characterization of a genetic variant of the steroid hormone-binding
      globulin gene in heterozygous subjects.
AB  - Steroid hormone-binding globulin in human serum displays different isoelectric
      focusing (IEF) patterns among individuals, suggesting genetic variation in the
      gene for this extracellular steroid carrier protein. Analysis of allele
      frequencies and family studies suggested the existence of two codominant alleles
      of the gene. Subsequent determination of the molecular basis of a variant of the
      gene was carried out using DNA from homozygous individuals from a single Belgian
      family. It was of interest to characterize other variant individuals to determine
      whether all variants identified by IEF phenotyping were caused by the same
      mutation or whether other mutations occurred in the gene in different
      populations. Previous studies identified Mexican subjects who were heterozygous
      for the variant IEF phenotype. Denaturing gradient gel electrophoresis was used
      to localize the mutation in these subjects and to purify the variant allele for
      DNA sequence analysis. The results show that the mutation in this population is
      identical to that identified in the Belgian family, and no other mutations were
      detected in the gene. These data represent the first analysis of steroid hormone
      binding globulin gene variation in heterozygous subjects and further support the
      conclusion of biallelism of the gene worldwide.

PMID- 7714099
TI  - Activation of T lymphocyte subsets by synthetic TSH receptor peptides and
      recombinant glutamate decarboxylase in autoimmune thyroid disease and insulin
      dependent diabetes.
AB  - We have postulated that a defect in specific antigenic induction of suppressor T
      lymphocytes may account for the immunoregulatory disorder in autoimmune thyroid
      disease. In this context, we have measured the proliferative responses of
      peripheral blood mononuclear cells (PBMC) to the synthetic peptides corresponding
      to the extracellular domain of the TSH receptor (TSHR) and recombinant glutamate
      decarboxylase (GAD65) by means of 3H thymidine incorporation. We have also
      studied the antigenic activation of CD4+ and CD8+ T lymphocytes by measuring
      human leukocyte antigen-DR (HLA-DR) expression on the cell surface by flow
      cytometric analysis. PBMC obtained from 47 patients with Graves' disease (GD)
      [including 19 hyperthyroid GD (hyper GD)], 18 with Hashimoto's thyroiditis (HT),
      7 with nontoxic nodular goiter (NG), 18 with insulin-dependent diabetes (IDDM),
      and 20 normal controls (N), were cultured for 7 days in the presence or absence
      of the pool peptides representing 3 different segments of TSHR or GAD65 at final
      concentration of 30 micrograms/mL or 10 micrograms/mL. The proportion of subjects
      whose PBMC gave a positive proliferative response with a stimulation index (SI)
      of over 2.3 (i.e. above the mean +2 SD for N) to TSHR peptides was significantly
      higher in the hyper GD group than among euthyroid GD (eu GD), HT, IDDM, and N
      group. The corresponding differences in mean SI provided analogous results,
      showing significant responses above normal in only hyper GD. The CD4+ T
      lymphocytes from hyper GD group were significantly more activated by TSHR
      peptides compared to eu GD, HT, IDDM, and N, and this induction correlated to
      their thyroid hormone levels. Quite differently, the activation of CD8+ T
      lymphocytes from both hyper GD and eu GD group in response to TSHR peptides was
      impaired compared to HT, IDDM, and the N group; in contrast to the findings with
      CD4+ T lymphocytes, this was independent of thyroid hormone levels. On the other
      hand, while the CD8+ T lymphocytes from GD and N groups were activated equally by
      GAD65, the activation of CD8+ T lymphocytes from the IDDM group by GAD65 was
      impaired compared to the GD and N groups. In conclusion, the activation of CD8+ T
      lymphocytes from GD and IDDM by relevant antigens (i.e. TSHR peptides for GD and
      GAD65 for IDDM) was impaired, but not by irrelevant antigens (i.e. GAD65 for GD
      and TSHR peptides for IDDM). There was also a modest stimulation of CD8+ T cells
      from all groups by tetanus toxoid and cardiac myosin light chain peptide, both
      irrelevant antigens.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714098
TI  - Occurrence and biological properties of a common genetic variant of luteinizing
      hormone.
AB  - We have characterized the frequency and selected biological properties of a
      variant form of LH caused by two point mutations in the gene of the LH beta
      subunit. Detection of the LH variant (or polymorphism) is based on aberrant
      immunoreactivity; it is not detected by a monoclonal antibody (Mab) recognizing a
      specific epitope in the LH alpha/beta-dimer (assay 1), but an assay using two LH
      beta-specific Mab recognizes this LH form normally (assay 2). Hence, the ratio of
      LH measured by assays 1 and 2 is 1.18-2.10 (range of mean +/- 2 SD) in wild-type
      subjects, 0.54-0.98 in heterozygotes, and below 0.15 in homozygotes with regard
      to the mutant LH beta allele. Analysis of sera from 249 healthy male and female
      subjects of Finnish origin revealed a frequency of 24.1% heterozygotes and 3.6%
      homozygotes for the mutation, with similar proportions in each sex. The ratio of
      in vitro bioactivity to immunoreactivity (assay 2) of the variant LH was
      significantly (P < 0.01) increased (2.9 +/- 0.1; n = 11) compared to that of wild
      type LH (2.2 +/- 0.1; n = 13). No difference was observed in LH pulsatility,
      measured from blood samples collected at 5-min intervals for 5 h, between three
      male and three female subjects homozygous for the LH variant and three matched
      male and three female controls with wild-type LH. Likewise, the responses of LH
      immunoreactivity (assay 2) to GnRH stimulation were similar with both types of
      LH. The half-time of the variant LH in rat circulation from both sexes was
      significantly shorter than that of LH from control subjects (males, 25.5 +/- 3.8
      vs. 48.3 +/- 2.7 min, respectively; P < 0.01; n = 3). Upon isoelectric focusing
      of peripheral serum samples, the isoform distribution of the variant LH was
      similar to that of wild-type LH. In conclusion, the LH variant discovered by us
      appears to occur with high frequency in the Finnish population (28% homo- or
      heterozygotes). It has increased in vitro bioactivity and a decreased half-time
      in vivo. These differences are compatible with a putative extra carbohydrate
      chain in the LH beta-chain, as one of the two mutations introduces an extra
      glycosylation signal. The subjects homozygous for the LH polymorphism are
      apparently healthy. However, the altered bioactivity and in vivo kinetics of the
      LH variant may induce subtle changes in LH action, either predisposing the
      affected individuals to or protecting them from disease conditions related to LH
      action.

PMID- 7714100
TI  - Human uterine decidual macrophages express renin.
AB  - Human uterine decidual tissue contains many cell types, including stromal cells,
      fibroblasts, and macrophages. Earlier studies have shown that decidualized
      uterine stromal cells express renin, primarily in the form of prorenin. However,
      the possibility that decidual macrophages, which comprise about 30% of the cells
      in term decidua, also express renin has not been investigated. To determine
      whether macrophages express renin, macrophages were isolated from enzymatically
      dispersed term decidual cells using immunomagnetic beads coupled to antibodies to
      human leukocyte antigen (HLA)-DR, an antigen present on macrophages, but not
      other decidual cells. The isolated cells were 92.1% CD14 positive and contained
      the messenger ribonucleic acids (mRNA) for the interleukin-2 type alpha receptor,
      but not for PRL, a specific marker of decidualized stromal cells.
      Immunocytochemical studies of the macrophage-enriched fraction demonstrated that
      the macrophages contained renin, and reverse transcription-polymerase chain
      reaction analysis with primers specific for renin indicated that the fraction
      also contained renin mRNA. Renin was detected in the conditioned medium of
      cultures of the macrophage-enriched preparations, greater than 90% of which was
      in the form of prorenin. As anticipated, renin and renin mRNA were also detected
      in the HLA-DR negative cells, more than 80% of which stained with specific
      antiserum to PRL. Peripheral mononuclear cells also expressed renin mRNA, as
      determined by reverse transcription-polymerase chain reaction analysis. These
      results demonstrate that human decidual macrophages express renin and indicate
      that renin is expressed by several cell types in decidual tissue.

PMID- 7714101
TI  - Do androgens regulate growth hormone-binding protein in adult man?
AB  - To determine whether adult serum GH-binding protein (GHBP) is regulated by
      androgen, serum GHBP concentrations were compared between 20 normal and 18
      hypogonadal men matched for age and body mass index, and the effect of im
      testosterone treatment (250 mg testosterone enanthate) on GHBP levels in the 18
      hypogonadal men was studied. Nine of the hypogonadal subjects had coexistent GH
      deficiency. Serum GHBP concentration was measured by a ligand immunofunctional
      assay. The mean serum GHBP level in untreated hypogonadal men was not
      significantly different from that of normal men (0.98 +/- 0.15 vs. 1.17 +/- 0.16
      nmol/L). The mean serum insulin-like growth factor I (IGF-I) level was
      significantly lower in the hypogonadal men (132 +/- 22 vs. 206 +/- 17 ng/mL; P <
      0.01). Basal testosterone (3.7 +/- 0.7 nmol/L) in hypogonadal men increased
      during treatment to a mean level of 29.1 +/- 2.8 nmol/L, which was not
      significantly higher than that in normal men (22.6 +/- 1.9 nmol/L). The mean
      serum GHBP level in hypogonadal men fell significantly during treatment to 0.60
      +/- 0.11 nmol/L (P = 0.0003), whereas the serum IGF-I level rose significantly to
      151 +/- 26 ng/mL (P < 0.04). The decrease in GHBP level was significant in both
      the GH-sufficient and GH-deficient subjects (P < 0.02 in both instances), whereas
      the increase in IGF-I level was significant in the GH-sufficient group (199 +/-
      22 to 235 +/- 29 ng/mL; P < 0.04) but not in the GH-deficient group (53 +/- 7 to
      55 +/- 5 ng/mL; P > 0.8). Thus, serum GHBP is normal in hypogonadal men but is
      reduced by testosterone treatment irrespective of endogenous GH-secretory status.
      It was concluded that the effect of testosterone on GHBP is pharmacological and
      occurs independent of GH mediation.

PMID- 7714102
TI  - Prevalence and clinical characterization of Japanese diabetes mellitus with an A
      to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene.
AB  - An A-to-G mutation at nucleotide position 3243 of the mitochondrial genome has
      been associated with insulin-dependent diabetes mellitus (IDDM) and with
      noninsulin-dependent diabetes mellitus (NIDDM) with deafness. We investigated the
      prevalence of this mutation in Japanese patients with IDDM, NIDDM, and impaired
      glucose tolerance (IGT) and in nondiabetic control individuals, and we identified
      it in 3 of 300 patients with NIDDM or IGT (1.0%). None of these individuals had
      significant sensorineural hearing loss. None of the 94 IDDM or the 115
      nondiabetic control subjects was positive for this mutation. Oral glucose
      tolerance test revealed that a 57-yr-old male with this mutation was rather
      hyperinsulinemic in the fasting state. The insulin secretion in this patient
      decreased with age; he did not complain of any hearing disorder, although
      audiometry revealed a slight elevation of hearing threshold at high frequencies.
      In conclusion, we found that a mitochondrial gene mutation at nucleotide position
      3243 was present in about 1% of NIDDM patients including those patients with IGT.
      The subtype of diabetes mellitus with this mutation may have a clinical profile
      similar to that found in patients with NIDDM commonly seen in outpatient clinics.

PMID- 7714103
TI  - Urinary excretion of galactosyl-hydroxylysine is a marker of growth in children.
AB  - Galactosyl-hydroxylysine (Gal-Hyl) is the predominant product of the
      posttranslational glycosylation of skeletal collagen. Urinary Gal-Hyl excretion
      is regarded as a marker of bone resorption in adults, but little information is
      available on the validity of this parameter in pediatric age groups. Using 24-h
      urine samples from 88 healthy children and adolescents ages 4-18 yr, reference
      ranges were established for this age group, and values were compared with
      measurements in children with overt GH deficiency (n = 14) or Ullrich-Turner
      syndrome (n = 21). When expressed relative to body weight (Gal-Hyl/wt), urinary
      Gal-Hyl excretion was 3.2 to 4.7 times higher in subjects 4-16 yr of age than in
      adults. Highest values were observed in very young children and during the
      pubertal growth spurt. In the total population, urinary Gal-Hyl/wt was closely
      related to growth velocity (r = 0.72) and significantly correlated with the
      urinary excretion of both hydroxyproline (r = 0.74) and deoxypyridinoline (r =
      0.88; P < 0.001 each). Urinary Gal-Hyl/wt was significantly lower in children
      with GH deficiency or Ullrich-Turner syndrome than in healthy children (P < 0.001
      each). The urinary excretion of Gal-Hyl was significantly correlated with growth
      velocity in GH-deficient children (r = 0.69; P = 0.004) but not in patients with
      Ullrich-Turner syndrome. In the latter, the increase in urinary Gal-Hyl excretion
      after 3 months of treatment with recombinant human GH correlated significantly
      with the increase in growth velocity after 12 months of treatment (r = 0.76; P =
      0.002). We conclude that the urinary excretion of Gal-Hyl is a valid and
      potentially useful index of skeletal growth in children.

PMID- 7714104
TI  - The role of the low dose (1 microgram) adrenocorticotropin test in the evaluation
      of patients with pituitary diseases.
AB  - The role of the low dose (1 microgram) ACTH stimulation test in the evaluation of
      patients with pituitary diseases was systematically assessed by relating its
      results to those obtained on gold standard tests of hypothalamo-pituitary-adrenal
      (HPA) reserve, such as insulin-induced hypoglycemia or a metyrapone challenge.
      Ten patients with pituitary diseases (8 men and 2 women) and proven impairment of
      HPA function and 9 patients (5 men and 4 women) with similar pituitary
      pathologies but preserved HPA function were studied (pituitary controls). A group
      of 7 normal volunteers (3 men and 4 women) served as normal controls. None of the
      subjects was taking glucocorticoids on a chronic basis or had been taking any
      recently. All subjects underwent ACTH tests at 0800 h with 3 different levels of
      stimulation (1, 5, and 250 micrograms), and serum cortisol was assayed 0, 30, and
      60 min after injection. A pass result was defined as a peak cortisol value of 497
      nmol/L or more. Basal cortisol values were indistinguishable among the groups.
      Pituitary controls did not differ from normal controls for any of the challenges.
      In healthy controls, peak cortisol levels attained with the low dose stimulation
      were clearly lower than with the standard dose (670 +/- 39 vs. 919 +/- 50 nmol/L;
      P = 0.002). However, every normal control passed the low dose stimulation,
      whereas none of the patients with impaired HPA function did (P = 0.00005).
      Although the cortisol values achieved on the standard (250 micrograms) dose by
      the subjects with impaired HPA function were significantly lower than those in
      normal controls (P < 0.005), they were generally normal in absolute terms.
      Indeed, using the peak value criterion, 7 of these 10 patients would have
      qualified as pass on the 5-micrograms challenge, and 9 of 10 would have passed
      the 250-micrograms test. Thus, the low dose ACTH test appears to perform better
      than the standard pharmacological test. As we have shown that this test
      correlates well with reference tests of HPA function, it is suggested that it
      should replace the standard ACTH test in the diagnosis of secondary adrenal
      insufficiency.

PMID- 7714105
TI  - Diagnosis of follicular thyroid lesions by proton magnetic resonance on fine
      needle biopsy.
AB  - Most thyroidectomies are currently performed for diagnostic purposes. It has been
      established that proton magnetic resonance spectroscopy (MRS) on excised thyroid
      tissue can distinguish normal thyroid from invasive carcinomas (P < 0.0001). The
      purpose of this study was to assess whether the same discrimination could be
      obtained preoperatively from fine needle biopsy (FNB). This has clinical
      importance because cytological examination of fine needle aspirates cannot
      distinguish between benign and malignant follicular thyroid lesions. Here we
      demonstrate a sensitivity of 95% for proton MRS to correctly identify clinically
      or histologically proven carcinoma. MRS measurements were made on FNB specimens
      (containing as few as 10(6) cells) from solitary thyroid nodules. MR assessment
      of FNB was inconsistent with that of the corresponding tissue in only 6.5% of
      cases. The discrimination between cancer and normal tissue was based on altered
      cellular chemistry measured as a one-dimensional spectral ratio of resonances
      from the amino acid lysine and lipid. Benign follicular lesions were separated
      into two groups: 67% with a spectral ratio similar to malignant thyroid tumors,
      and 33% with a spectral ratio comparable to that in normal thyroid tissue. Thus,
      in contrast with histopathology, MRS offers a method for assessment of FNB of
      follicular lesions with the potential to identify a biologically benign group,
      which could avoid thyroid surgery for purely diagnostic purposes.

PMID- 7714106
TI  - In vivo metabolic effects of insulin-like growth factor-I not mediated through
      the insulin receptor.
AB  - Patients with mutations affecting insulin receptor function may maintain some
      degree of metabolic control. The hypothesis has been put forth that in these
      patients, fuels may be metabolized through pathways (i.e. receptor activation)
      that become relevant in such abnormal conditions. The aim of our study was to
      evaluate the metabolic effects of insulin-like growth factor-I (IGF-I) in a 19-yr
      old patient with homozygous mutation of the insulin receptor alpha-subunit. Her
      metabolic and hormonal features were marked hyperglycemia (11-33 mmol/L) and
      hyperinsulinemia (1000-2000 pmol/L); normal free fatty acids and lactate; low IGF
      I; glycerol, alanine, and pyruvate below the normal range; and elevated beta
      hydroxybutyrate. Unlike diabetic ketoacidosis, no triglyceride or protein
      breakdown was present, suggesting a compensatory mechanism, possibly sustained by
      the insulin concentration acting on IGF-I receptors. Subcutaneous administration
      of IGF-I (40, 80, and 120 micrograms/kg), although not affecting plasma glucose,
      resulted in a rapid decrease in free fatty acids and prevented the rise of beta
      hydroxybutyrate levels compared to placebo. Therefore, IGF-I can exert direct
      metabolic effects in vivo, probably through activation of its own receptor, even
      at a concentration not affecting blood glucose levels. Furthermore, these
      findings are consistent with the hypothesis that IGF-I receptors may be activated
      by high insulin levels, providing lipid and protein regulation in patients with
      nonfunctional insulin receptors.

PMID- 7714107
TI  - Dexamethasone inhibition of interferon-alpha 2-induced stimulation of cortisol
      and growth hormone secretion in chronic myeloproliferative syndrome.
AB  - This study investigated the acute effects of interferon-alpha 2 (IFN-alpha 2) on
      hormonal secretion in adult patients affected by a chronic myeloproliferative
      syndrome and tried to shed some light on the mechanism by which IFN-alpha 2
      stimulates cortisol and GH secretion in humans. We compared the pattern of IFN
      alpha 2-induced cortisol and GH release with that elicited after the same
      challenge given subsequent to pretreatment with dexamethasone (Dex). We studied
      eight patients affected by a chronic myeloproliferative syndrome
      (thrombocythemia) who had been selected for treatment with IFN-alpha 2. Four sets
      of experiments were performed: 1) 2 mL iv saline was given at 0800 h in eight
      cases; 2) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h in eight cases; 3) 3 x
      10(6) IU iv IFN-alpha 2 was given at 0800 h after pretreatment with 1.5 mg Dex (1
      mg at midnight the previous night and 0.5 mg at 0700 h on the day of the test) in
      six cases; and 4) 2 mL iv saline was given at 0800 h after the same Dex
      pretreatment in four cases. Cortisol and GH were measured in plasma samples drawn
      at 30-min intervals between 0800 and 1300 h. Acute iv administration of IFN-alpha
      2 stimulated the release of both cortisol and GH in each patient with a
      significant increment vs. control values, as assessed by areas under the curve.
      The administration of Dex significantly decreased basal plasma cortisol secretion
      and abolished cortisol response to IFN-alpha 2 administration. These data suggest
      that the stimulatory action of IFN-alpha 2 on cortisol release is mediated via a
      modulation of the activity of the hypothalamic-pituitary axis rather than through
      a direct effect at the level of the adrenal cortex. After Dex plus saline
      administration, no significant effect was observed on plasma GH levels, which
      remained low. Dex administration significantly decreased GH response to IFN-alpha
      2. These data suggest that a hypothalamic or pituitary stimulation (or both) is
      involved in the mechanism of IFN-alpha 2-induced GH secretion. It remains to be
      established whether IFN-alpha 2 directly stimulates pituitary somatotropic cells
      or whether the cytokine exerts a stimulatory action on GH secretion by indirectly
      modulating the hypothalamic or pituitary activity. In conclusion, acute iv
      administration of IFN-alpha 2 represents a potent stimulus for cortisol and GH
      secretion in adult human subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714108
TI  - Interleukin-1 receptor blockade does not affect endotoxin-induced changes in
      plasma thyroid hormone and thyrotropin concentrations in man.
AB  - Interleukin-1 (IL-1) has been implicated as a mediator of the euthyroid sick
      syndrome. The effects of IL-1 can be blocked by the naturally occurring IL-1
      receptor antagonist (IL-1ra). In the present study, iv administration of
      endotoxin was used as a human model of the euthyroid sick syndrome. To assess the
      role of endogenous IL-1 in endotoxin-induced changes in plasma thyroid hormone
      and TSH concentrations, 18 healthy postabsorptive humans were studied on a
      control study day, followed 3 days later by a study day on which they were
      randomly assigned to one of three treatments: a 6-h infusion of recombinant human
      IL-1ra alone (133 mg/h), endotoxin alone (lot EC-5; 20 U/kg), or both endotoxin
      and IL-1ra. Administration of IL-1ra alone did not affect the plasma
      concentrations of thyroid hormones or TSH compared with those on the control day.
      Endotoxin injection was associated with decreases in T4 (P = 0.06 vs. the control
      day), free T4 (P = 0.02), T3 (P < 0.001), and TSH (P < 0.0001) and a rise in rT3
      (P < 0.001), reproducing the major features of the euthyroid sick syndrome.
      Coinfusion of IL-1ra did not influence these endotoxin-induced changes. Our
      results suggest that endogenous IL-1 does not play an important role in the
      alterations in plasma thyroid hormone and TSH concentrations induced by mild
      endotoxemia in healthy humans.

PMID- 7714109
TI  - Genetic alterations in thyroid hyperfunctioning adenomas.
AB  - Thirty-seven thyroid autonomously hyperfunctioning adenomas were screened for
      mutations in the TSH receptor (TSHR), G alpha s (gsp), and ras genes. Polymerase
      chain reaction-amplified fragments of the TSHR C-terminal part (exon 10), the G
      alpha s (exons 8 and 9), and the three ras genes were obtained from the genomic
      DNA extracted from 37 tumors and their adjacent normal tissues and were studied
      by direct nucleotide sequencing and hybridization with synthetic probes. A point
      mutation in the third intracellular loop (codon 623) of the TSHR was found in 3
      of 37 adenomas studied. This mutation codes for a change (Ala to Ser) in the TSHR
      structure and is somatic and heterozygotic. Constitutive activation of the TSHR
      was demonstrated by an increase in basal cAMP levels after transfection of
      Chinese hamster ovary cells with a mutated Ser623-TSHR complementary DNA. Nine
      gsp[00ae]MDRV[00af]- and one ras-activating mutations were also detected. No
      simultaneous alteration of the studied genes was present. Thus, in
      hyperfunctioning thyroid adenomas, our data suggest that a mutational activation
      of the TSHR and gsp genes may play a tumorigenic role through constitutive
      activation of the cAMP pathway.

PMID- 7714110
TI  - Two novel mutations in the coding region for neurophysin-II associated with
      familial central diabetes insipidus.
AB  - Familial central diabetes insipidus is an autosomal dominant disease caused by a
      deficiency of arginine vasopressin (AVP). We previously reported three distinct
      mutations in the AVP gene in Japanese familial central diabetes insipidus
      pedigrees that result in a substitution of Ser for Gly57 in the neurophysin-II
      (NPII) moiety of the AVP precursor, a substitution of Thr for Ala at the COOH
      terminus of the signal peptide, and a deletion of Glu47 in the NPII moiety. In
      this study, we analyzed the AVP gene in two pedigrees by direct sequencing of the
      polymerase chain reaction-amplified DNA and found two novel mutations in exon 2,
      which encodes the central part of the NPII moiety of the precursor. The mutation
      in one pedigree was a C to A transition at nucleotide position 1891, which
      replaces Cys67 (TGC) with stop codon (TGA). As the premature termination
      eliminates part of the COOH domain of the NPII moiety and the glycoprotein
      moiety, the conformation of the truncated protein is likely to be markedly
      different from that of normal precursor. In another pedigree, a G to T
      transversion was detected at nucleotide position 1874, which substitutes polar
      Trp (TGG) for hydrophobic Gly62 (GGG). It is possible that mutated NPII
      molecules, as a consequence of a conformational change, cannot bind AVP or self
      associate to form higher oligomer complexes. Interestingly, all mutations we have
      identified to date, with the exception of the signal peptide mutation, are
      located in exon 2, suggesting the importance of the highly conserved central part
      of the NPII molecules and/or the NPII moiety in the precursor for AVP synthesis.

PMID- 7714111
TI  - Growth hormone hypersecretion in a girl with McCune-Albright syndrome: comparison
      with controls and response to a dose of long-acting somatostatin analog.
AB  - GH every 20 min for 24 h, insulin-like growth factor I (IGF-I), IGF-binding
      protein 3, and estradiol (E2) were measured in a 7.3-yr-old girl with precocious
      puberty due to McCune-Albright syndrome (MAS) who developed stigmata of early
      acromegaly and in 9 other MAS patients who had no signs of acromegaly. To
      determine whether the MAS patients had subtle abnormalities in GH secretion, a
      computerized pulse analysis program was used to compare the MAS data with those
      from 27 control girls with central precocious puberty who had a similar rate of
      bone age advance, E2, and body mass index. We found no differences in mean GH, GH
      pulse frequency, pulse height, or pulse area between MAS patients and controls
      except in patient 1, who had an elevated mean +/- SD GH compared with controls
      (15.4 +/- 2 vs. 4.8 +/- 2.3 micrograms/L; P < 0.01) and an elevated IGF-I (908
      micrograms/L) and IGF-binding protein 3 (5.6 mg/L). None of the GH parameters
      correlated with body mass index, age, bone age, or E2 levels in either group. The
      serum GH in patient 1 fell to near-undetectable levels from 60-180 min after a
      100-micrograms sc dose of long-acting somatostatin, confirming that this form of
      therapy can be effective in cases of GH hypersecretion due to MAS.

PMID- 7714112
TI  - Serum follistatin levels in women: evidence against an endocrine function of
      ovarian follistatin.
AB  - Follistatin is a monomeric protein first identified in and isolated from ovarian
      follicular fluid. Evidence that follistatin might be an ovarian endocrine hormone
      functioning in a negative feedback fashion to modulate pituitary FSH production
      is based primarily on in vitro experiments. To examine the possible role of
      follistatin as an endocrine agent in vivo, we sought to relate circulating levels
      of follistatin to ovarian activity in women. Therefore, we developed a specific
      and sensitive homologous RIA using antiserum generated against recombinant human
      follistatin for the measurement of total follistatin in the presence or absence
      of activin. Follistatin was measured quantitatively (106 +/- 6% recovery) using
      calibration standards ranging from 0.4-25 ng/tube and up to 400 microL/tube
      serum. Furthermore, all of the endogenous follistatin measured in human serum
      could be removed by adsorption to activin-coated plates. Using this homologous
      RIA, human follicular fluid (100-600 ng/mL; n = 75) contained 3-150 times more
      follistatin than serum (4-35 ng/mL), an observation consistent with the notion
      that serum follistatin originates from the gonad. However, further studies of
      follistatin levels across the normal menstrual cycle (mean +/- SE, 8.09 +/- 0.73;
      n = 72 daily samples from 4 women), in pregnant women (17.49 +/- 1.34; n = 8), in
      daily samples from 20 women undergoing ovarian stimulation by exogenous FSH (9.90
      +/- 0.62; n = 119), in postmenopausal women including two ovariectomized
      individuals (9.57 +/- 0.43; n = 8), and in GnRH-deficient women (9.85 +/- 0.50; n
      = 6) failed to support the hypothesis that serum levels of follistatin reflect
      ovarian activity in women. Levels of follistatin measured in serum collected
      across normal menstrual cycles did not fluctuate. However, the roughly nanomolar
      concentrations of follistatin measured suggest a physiological role for this
      protein. Follistatin at nanomolar concentrations may be capable of binding and
      inactivating circulating activin and perhaps in this way limiting the biological
      activity of activin to local autocrine or paracrine mechanisms. Measurement of
      peripheral levels of follistatin apparently represents only a first, albeit
      crucial, step in the study of the physiological significance of this protein in
      human reproduction.

PMID- 7714113
TI  - Effects of insulin on plasma magnesium in noninsulin-dependent diabetes mellitus:
      evidence for insulin resistance.
AB  - Insulin influences both glucose metabolism and magnesium homeostasis in humans.
      The present studies sought to determine whether insulin-induced stimulation of
      magnesium uptake is impaired in noninsulin-dependent diabetes mellitus (NIDDM)
      and enhanced by acute hyperglycemia. To do so, we measured plasma magnesium
      concentrations in diabetic and nondiabetic subjects on two occasions: once when
      glucose concentrations were maintained constant and once when glucose
      concentrations were varied to mimic a postprandial pattern. The same amount of
      insulin was infused on both occasions in a manner that reproduced the systemic
      insulin concentrations normally observed after glucose ingestion. During the
      prandial insulin infusion, the decrement in the plasma magnesium concentration
      was lower (P < 0.05) in the diabetic patients than that in the nondiabetic
      subjects during both the euglycemic (4.1 +/- 0.9 vs. 7.8 +/- 1.3 mmol/L.4 h) and
      hyperglycemic (1.7 +/- 1.1 vs. 6.6 +/- 1.4 mmol/L.4 h) studies. Glucose
      disappearance also was lower (P < 0.05) in the diabetic patients than that in the
      nondiabetic subjects, and the insulin-induced decrement in plasma magnesium was
      correlated (P < 0.01) with glucose disappearance. On the other hand, despite
      higher (P < 0.05) rates of disappearance in the hyperglycemic than euglycemic
      experiments, the decrement in plasma magnesium did not differ in either group on
      either occasion. We conclude that insulin resistance in subjects with NIDDM
      impairs the ability of insulin to stimulate magnesium as well as glucose uptake.

PMID- 7714114
TI  - Intracellular magnesium and insulin resistance: results in Pima Indians and
      Caucasians.
AB  - Intracellular magnesium is a cofactor for numerous enzymes involved in
      carbohydrate metabolism. Magnesium accumulation is dependent upon insulin action
      and correlates with insulin-mediated glucose uptake. As Pima Indians are known to
      be insulin resistant, we investigated whether, in response to insulin infusion,
      they have lower erythrocyte magnesium accumulation than Caucasians. Insulin
      mediated glucose uptake was determined by a euglycemic hyperinsulinemic glucose
      clamp in 29 obese nondiabetic volunteers: 15 Caucasians (8 males and 7 females)
      and 14 Pima Indians (8 males and 6 females). Pima Indians were younger than
      Caucasians (mean +/- SD, 28 +/- 7 vs. 39 +/- 8 yr; P < 0.01), but had similar
      body mass index and fasting/2-h plasma glucose concentrations. Despite higher
      steady state plasma insulin levels (692 +/- 260 vs. 540 +/- 70 pmol/L; P < 0.03),
      Pima Indians had lower insulin-mediated glucose uptake than Caucasians (108 +/-
      20 vs. 244 +/- 32 mg/m2.min; P < 0.0001). The mean fasting plasma magnesium
      concentration was lower in Pima Indians than in Caucasians (0.79 +/- 0.05 vs.
      0.85 +/- 0.06 mmol/L; P < 0.01), whereas the mean fasting erythrocyte magnesium
      concentrations (1.98 +/- 0.10 vs. 2.03 +/- 0.14 mmol/L) were similar in the 2
      groups. In response to insulin infusion, erythrocyte magnesium content increased
      less in Pima Indians than in Caucasians (0.15 +/- 0.07 vs. 0.28 +/- 0.21 mmol/L;
      P < 0.03). However, this increase was similar in the 2 groups when values were
      adjusted for insulin-mediated glucose uptake. In conclusion, nondiabetic Pima
      Indians have a lower erythrocyte magnesium accumulation in response to insulin
      infusion; this is probably due to their high degree of insulin resistance. The
      biochemical and physiological consequences of decreased intracellular magnesium
      uptake are discussed.

PMID- 7714115
TI  - Somatostatin receptor subtype gene expression in pituitary adenomas.
AB  - Somatostatin (SRIF) exerts its diverse biological effects through a family of
      membrane receptors. In addition to inhibiting GH secretion, SRIF has
      antiproliferative effects and has been used clinically in the treatment of
      pituitary tumors. SRIF receptor (SSTR) expression has recently been identified in
      pituitary adenomas, and it is unknown whether differential expression of SSTR
      subtypes predicts clinical responses to SRIF analogs. We therefore determined
      which SSTR subtype messenger RNAs (mRNAs) are expressed in pituitary adenoma
      phenotypes and in normal human pituitary tissue using reverse transcriptase
      polymerase chain reaction and tested whether expression of specific SSTR subtype
      mRNA is necessary for SRIF inhibition of GH secretion in human somatotroph
      adenomas in vitro. Expression of SSTR subtypes 1, 2, and 5 mRNA was identified in
      all pituitary adenoma types and normal pituitary tissue. In contrast, SSTR3 mRNA
      was detected in only one somatotroph adenoma as well as in control insulinoma
      tissue, a tissue known to express SSTR3 mRNA, and was not detected in normal
      pituitary tissue. SSTR4 mRNA was not detected in any human pituitary tissue. To
      determine whether specific SSTR subtype mRNA expression is required for SRIF
      inhibition of GH secretion, five somatotroph adenomas were treated with 10(-7)
      mol/L SRIF in vitro, and significant inhibition of GH release occurred in all
      adenomas. All five tumors expressed SSTR2 mRNA and SSTR5 mRNA, and three
      expressed SSTR1 mRNA. The absence of SSTR1 mRNA expression did not affect the
      ability of SRIF to suppress GH secretion. We conclude that: 1) human pituitary
      adenomas and normal pituitary express multiple SSTR gene transcripts; 2) SSTR5
      mRNA, which has not been reported in other human endocrine tumor types, is
      expressed in neoplastic and normal pituitary tissue; and 3) SSTR2 mRNA, SSTR5
      mRNA, and variable SSTR1 mRNA are expressed in GH-secreting tumors, which are
      responsive to SRIF in vitro. Further understanding of SSTR gene expression in
      pituitary adenomas will facilitate our understanding of the pathogenetic
      mechanisms of tumorigenesis and may provide a rationale for the use of specific
      SRIF analogs for clinical application.

PMID- 7714116
TI  - Relationship of proinsulin and insulin with noninsulin-dependent diabetes
      mellitus and coronary heart disease in Japanese-American men: impact of obesity-
      clinical research center study.
AB  - Obesity is associated with noninsulin-dependent diabetes mellitus (NIDDM) and
      coronary heart disease (CHD), and these interactions have usually been related to
      changes in immunoreactive insulin (IRI) levels. A role of proinsulin (PI) in this
      association has been suggested. We, therefore, examined IRI, PI, and true insulin
      levels and the PI/IRI ratio by glucose tolerance or CHD status in a cross
      sectional study of 170 Japanese-American men (45-74 yr old) in whom 2 measures of
      adiposity (body mass index and intraabdominal fat) were made to assess potential
      associations in this population with a high prevalence of both NIDDM and CHD.
      Subjects were classified as having normal glucose tolerance (n = 58), impaired
      glucose tolerance (IGT; n = 55), or NIDDM (n = 57) or were classified by CHD
      status (without CHD, n = 127; with CHD, n = 43). A positive linear relationship
      existed between obesity, determined either as the body mass index or
      intraabdominal fat, and IRI, PI, and true insulin, but not the PI/IRI ratio. In
      the NIDDM subjects, PI levels were disproportionately greater than those in
      subjects with normal glucose tolerance or IGT, so the PI/IRI ratio was
      significantly greater in the NIDDM group [mean (95% confidence interval): normal
      glucose tolerance, 11.8% (range, 10.4-13.5); IGT, 12.8% (range, 10.8-15.1);
      NIDDM, 19.2% (range, 15.4-24.0); P = 0.0002] even when adjusted for obesity (P =
      0.0004). In subjects with CHD compared to subjects without CHD, IRI (P = 0.0026)
      and true insulin levels (P = 0.0043) were increased, but PI levels were not.
      However, these differences were not present after adjustment for obesity. In
      contrast, when intraabdominal fat was adjusted for IRI or true insulin, a
      significant effect of intraabdominal fat on CHD risk was maintained (P = 0.045
      and P = 0.029, respectively), suggesting that another factor(s) associated with
      central obesity may be involved in CHD risk. Thus, in Japanese-American men,
      elevated PI and PI/IRI ratio are markers of B-cell dysfunction, and these are not
      the result of obesity. An elevated true insulin level is present in those with
      CHD, but this appears to be the result of obesity. In contrast, central adiposity
      confers an additional risk for CHD independent of insulin.

PMID- 7714117
TI  - Lack of increased risk for extracranial, nonleukemic neoplasms in recipients of
      recombinant deoxyribonucleic acid growth hormone.
AB  - This report describes cases of new extracranial nonleukemic neoplasms in
      recombinant human GH (rhGH) recipients. The data are largely from the National
      Cooperative Growth Study (NCGS), with over 51,000 patient-years at risk from
      12,209 patients treated with Protropin rhGH. In addition to case reports of
      extracranial tumors from the NCGS enrollees, there have been reports from non
      NCGS patients. Ten cases of new extracranial neoplasms have been reported from
      this total study population, and there have been eight cases whose second
      neoplasms were extracranial in nature. For the new cases, the number of observed
      cases is compared with the number of expected cases, as derived from incidence
      rates published by the National Cancer Institute's SEER (Surveillance,
      Epidemiology, and End Results) Program. The standard morbidity ratio (SMR),
      defined as the number of observed cases/expected cases, is calculated for males
      and females separately, with further subgroup analysis based upon age. For the
      NCGS population, the SMRs were not statistically distinguishable from unity (i.e.
      1). When the number of non-NCGS Protropin patients is estimated and SMRs are
      calculated for the total Protropin-treated group, the SMRs remain statistically
      indistinguishable from one. At present, these data suggest that rhGH does not
      increase the risk for developing nonleukemic extracranial neoplasms. Because a
      small number of additional cases could significantly alter the SMR calculations,
      meticulous reporting and continued surveillance must continue.

PMID- 7714119
TI  - Twenty-four-hour mean plasma testosterone concentration declines with age in
      normal premenopausal women.
AB  - The 24-h mean plasma concentration of total testosterone (T) was measured in 33
      healthy, regularly cycling, nonobese women between 21 and 51 yr of age. Percent
      free T was measured in 17 of them. Plasma dehydroepiandrosterone (DHEA) and
      dehydroepiandrosterone sulfate (DHEAS) were measured in 24 of them, and the DHEA
      to-T and DHEAS-to-T ratios were calculated. It was found that the concentration
      of total T showed a steep decline with age; the regression equation was: T
      (nanomoles per L) = 37.8 x age-1.12 (r = -0.54; P < 0.003). According to this
      equation, the expected T concentration of a woman of 40 would be 0.61 nmol/L,
      about half that of a woman of 21 (1.3 nmol/L). The percent free T did not vary
      significantly with age, so free T concentration likewise showed a steep decline
      with age. The DHEA-to-T and DHEAS-to-T ratios were both age invariant, clearly
      because the levels of DHEA and DHEAS also decline steeply with age, as previously
      reported.

PMID- 7714118
TI  - Characterization of the somatostatin receptor subtype in a bronchial carcinoid
      tumor responsible for Cushing's syndrome.
AB  - Small ACTH-secreting carcinoid tumors responsible for Cushing's syndrome are
      often difficult to localize using available radiological investigations.
      Somatostatin receptors have been found in about 90% of carcinoid tumors studied,
      leading to a new approach for the localization of tumors or metastasis by using
      radiolabeled somatostatin analogs. We report a case of Cushing's syndrome due to
      an ACTH-secreting bronchial carcinoid tumor, completely suppressible with
      octreotide treatment and evidenced by body scintigraphy with 111In-labeled
      pentreotide. After removal, which led to patient recovery, the tumor was studied
      in vitro. In situ hybridization, using a complementary DNA probe, revealed POMC
      messenger ribonucleic acid in a subpopulation of tumor cells. These cells were
      labeled by immunochemistry using an antiserum directed against ACTH. Confocal
      laser scanning microscopy analysis showed that the ACTH-immunoreactive peptide
      was sequestered in secretory granules. Autoradiographic labeling using [125I
      Tyrzero,D-Trp8]somatostatin-14 demonstrated the presence of somatostatin-binding
      sites in the whole tumor tissue. The relative affinities of various selective
      somatostatin analogs and the ability of GTP to inhibit radioligand binding
      suggested that the receptor expressed in the tumor cells belonged to the SSTR-2
      subtype.

PMID- 7714120
TI  - Dysregulation of interleukin-6 responses in ectopic endometrial stromal cells:
      correlation with decreased soluble receptor levels in peritoneal fluid of women
      with endometriosis.
AB  - Endometriosis (EM) is characterized by the aberrant growth of endometrial cells
      at sites outside the uterus. We showed previously that peritoneal leukocyte
      interleukin-6 (IL-6) production is altered in women with EM relative to that in
      normal control women. Because studies suggest that IL-6 may be growth regulatory
      for endometrial cells, we examined IL-6 and IL-6 soluble receptor (IL-6sR) in the
      peritoneal fluid of 40 women. In addition, the growth responsiveness of ectopic
      endometrial stromal cells to IL-6 was evaluated. The severity of EM correlated
      with increased levels of IL-6 accompanied by decreased IL-6sR in peritoneal fluid
      (controls, 1.0 +/- 0.1 and 525.4 +/- 53; stage I-II EM, 1.4 +/- 0.2 and 274.6 +/-
      26; stage III-IV EM, 19.3 +/- 4.6 and 319.4 +/- 26; adhesions, 1.9 +/- 0.4 and
      324.7 +/- 26 pmol/L IL-6 and IL-6sR, respectively). Additional studies revealed
      that unstimulated endometrial stromal cells from ectopic implants secreted this
      cytokine in vitro. Furthermore, these cells were resistant to growth inhibition
      induced by exposure to additional IL-6; this response correlated with weak
      expression of IL-6 receptor. Taken together, these findings lend further support
      to the hypothesis that dysregulation of IL-6 responses plays a role in the
      pathophysiology of EM.

PMID- 7714121
TI  - Nongenomic effects of 17 beta-estradiol on maturing human oocytes: relationship
      to oocyte developmental potential.
AB  - There is increasing evidence for nongenomic steroid effects in various cell
      types. This study is the first to demonstrate that 17 beta-estradiol (E2) exerts
      a direct nongenomic effect on maturing human oocytes by inducing a series of
      transient increases in the intracellular free calcium concentration ([Ca2+]i).
      This effect of E2 appeared to be specific and was mediated by steroid action on
      the cell surface. The first of the E2-induced [Ca2+]i increases was induced by an
      influx of extracellular Ca2+ ions. However, the release of Ca2+ from
      intracellular stores contributed more significantly to [Ca2+]i waves
      characterizing the subsequent series of secondary [Ca2+]i increases, although the
      presence of extracellular Ca2+ still was an absolute requirement for these
      [Ca2+]i oscillations. The addition of E2 to oocyte maturation medium did not
      produce any apparent effects on either germinal vesicle breakdown or further
      progression of meiosis, but it did increase the fertilization and cleavage rates
      of the in vitro matured oocytes. These findings show that E2 can directly
      influence the quality of maturing oocytes. This effect is due to steroid action
      on the cell surface, implies Ca2+ as a second messenger, and contributes to
      oocyte capacitation for fertilization and early postfertilization development.

PMID- 7714122
TI  - Expression of luteinizing hormone and chorionic gonadotropin receptor messenger
      ribonucleic acid in human corpora lutea during menstrual cycle and pregnancy.
AB  - In the present study, we examined the expression of LH and CG receptor messenger
      RNA (mRNA) in human corpora lutea (CL) during the menstrual cycle and pregnancy.
      Poly(A)-enriched RNA was extracted from CL and analyzed by Northern and slot
      blots, using a radiolabeled complementary RNA probe derived from the human LH
      receptor complementary DNA. Northern blot analysis indicated the presence of
      multiple LH receptor mRNA transcripts with molecular sizes of 8.0, 7.0 and 4.5
      kilobases in human CL during the menstrual cycle. The predominant transcript was
      4.5 kilobases in size. However, no hybridization signals were observed in
      nongonadal tissues (heart, liver, and kidney). Densitometric analyses revealed
      that the levels of LH receptor mRNA increased from early luteal phase to
      midluteal phase and subsequently decreased during late luteal phase. After the
      onset of menstruation, the LH receptor mRNA level was undetectable in the
      regressing CL. Moreover, radioligand receptor assay (RRA) showed a close
      parallelism between LH receptor mRNA levels and LH receptor content in CL
      throughout the menstrual cycle. LH receptor mRNA expression was also found in CL
      during early pregnancy. The level of LH receptor mRNA was relatively high in
      early pregnancy CL, whereas LH receptor content was low. Using in situ
      hybridization, LH receptor mRNAs were uniformly expressed in both large and small
      luteal cells during early and midluteal phase and early pregnancy, but not in
      regressing CL. In conclusion, these data demonstrate that the regulation of LH
      receptor content in human CL during luteal phase is associated with similar
      changes in the receptor message levels, suggesting the physiological roles for LH
      receptor mRNA during the menstrual cycle in the human. In addition, the
      expression of LH receptor mRNA was demonstrated in human CL during early
      pregnancy.

PMID- 7714123
TI  - Leukemia inhibitory factor produced at the fetomaternal interface stimulates
      chorionic gonadotropin production: its possible implication during pregnancy,
      including implantation period.
AB  - We investigated the role of leukemia inhibitory factor (LIF) at the implantation
      site of human embryos. The first trimester decidual tissue produced higher levels
      of LIF than chorionic tissue, but the decidua produced much smaller amounts of
      interleukin-6 (IL-6) than the chorion in vitro, as determined by enzyme-linked
      immunosorbent assay. The reverse transcription-polymerase chain reaction and
      immunohistochemical analysis revealed the expression and localization, on the
      trophoblasts, of glycoprotein 130 (gp130), an IL-6 signal transducer receptor
      component shared by the cytokines such as LIF and IL-6. Trophoblasts stimulated
      by recombinant LIF (rLIF) produced CG titer at the amount similar to that induced
      by rIL-6. Recombinant LIF-induced CG production was significantly blocked by anti
      gp130 antibody but not by anti-IL-6 receptor antibody, whereas rIL-6-induced CG
      was completely blocked by both antibodies. Recombinant LIF- and rIL-6-induced CG
      productions were both significantly blocked by genistein, a tyrosine kinase
      inhibitor, suggesting an involvement of tyrosine kinase in gp130-mediated CG
      production. Since CG is capable of stimulating trophoblast growth and
      differentiation as well as placental metabolism, LIF produced at the fetomaternal
      interface are considered to stimulate the trophoblasts to produce CG, which may
      contribute to the maintenance of the placental functions and embryonal growth.

PMID- 7714124
TI  - Age-related course of urinary gonadotropins in children.
AB  - Serum levels of LH and FSH are very low from about 2 yr of age to the onset of
      puberty, which is heralded by a very sharp increase in LH levels. We studied age
      related changes in urinary gonadotropins in a total of 184 boys and girls of
      various ages. Urinary FSH and LH were measured by ultrasensitive time-resolved
      immunofluorometric assays. The detection limit was 0.015 IU/L for LH and 0.018
      IU/L for FSH. We observed that after an initial drop following the first months
      of life, urinary LH levels stayed below 0.5 IU/L until age 9 yr in girls and
      below 1.0 IU/L until age 11 yr in boys, whereas mean urinary FSH levels remained
      below 3.0 IU/L until age 10 yr in girls and 12 yr in boys. During puberty, mean
      urinary FSH and LH concentrations increased to about 5 IU/L in boys and 10 IU/L
      in girls. This corresponds to a 5-fold increase in FSH in both sexes and a 50- to
      100-fold increase in LH in boys and girls, respectively. These dynamic changes
      agree with previous reports regarding serum levels, suggesting that noninvasive
      urinary gonadotropin measurements can be a viable alternative to serum
      determinations in the evaluation of gonadotropin secretion during childhood and
      adolescence.

PMID- 7714125
TI  - Human monoclonal autoantibodies against the immunodominant region on thyroid
      peroxidase: lack of cross-reactivity with related peroxidases or thyroglobulin
      and inability to inhibit thyroid peroxidase enzymatic activity.
AB  - Thyroid peroxidase (TPO) autoantibodies are heterogeneous and have been
      classified in terms of whether they cross-react with myeloperoxidase (MPO),
      lactoperoxidase (LPO), or thyroglobulin (Tg) as well as by whether they inhibit
      TPO enzymatic activity. Four human monoclonal TPO autoantibodies, generated using
      combinatorial immunoglobulin gene libraries and expressed as F(ab), have been
      used to investigate these properties of TPO autoantibodies. The binding of F(ab)
      WR1.7, TR1.8, TR1.9, and SP1.4 to 125I-labeled recombinant TPO was inhibited 50%
      by approximately 10(-10) mol/L unlabeled TPO, reflecting the high affinities of
      these F(ab) for TPO. In contrast, F(ab) binding to TPO was unaffected by human
      MPO (both native and reduced), bovine LPO, or human Tg at concentrations up to
      10(-8) mol/L. Further, TPO enzymatic activity, measured by guiacol oxidation, was
      unaffected by preincubation with the four F(ab) individually or as a pool (each
      at 10(-8) mol/L). In conclusion, four human TPO monoclonal autoantibodies do not
      cross-react with related peroxidases or Tg, nor do they inhibit TPO enzymatic
      activity. These monoclonal immunoglobulin G class autoantibodies define the
      immunodominant region on TPO and represent about 85% of TPO autoantibodies in an
      individual patient's serum. Consequently, our data suggest that TPO
      autoantibodies that cross-react with MPO, LPO, or Tg, or inhibit TPO enzymatic
      activity are likely to bind outside the immunodominant region.

PMID- 7714126
TI  - A pathologist's comments on diagnosis of thyroid nodules by fine needle
      aspiration.

PMID- 7714127
TI  - Is mild endometriosis a condition occurring intermittently in all women?

PMID- 7714128
TI  - New clinical guidelines are needed for the treatment of endometriosis.

PMID- 7714129
TI  - Endometriosis does not exist; all women have endometriosis.

PMID- 7714131
TI  - Classification of endometriosis. Improving the classification of endometriotic
      ovarian cysts.

PMID- 7714130
TI  - Is mild endometriosis a progressive disease?

PMID- 7714132
TI  - Endoscopic exploration and classification of the chocolate cysts.

PMID- 7714133
TI  - Classification of endometriosis. The need for modification.

PMID- 7714134
TI  - Are spermatid injections into human oocytes now mandatory?

PMID- 7714135
TI  - Utero-cervical inhibitory reflex. The description of a reflex and its clinical
      significance.
AB  - The functional relationship of the uterine corpus to the cervix was studied in 14
      healthy women. The uterus was stimulated by an electro-myographic (EMG) needle
      electrode and the cervical pressure recorded by a balloon-tipped catheter. The
      test was repeated in seven women after the uterus had been anaesthetized. In the
      other seven patients, the response of both the uterine EMG and pressure to
      cervical dilatation was registered. The EMG needle electrode was then inserted
      into the cervix and the uterine pressure response to both stimulation and
      dilatation of the non-anaesthetized and anaesthetized cervix was recorded.
      Uterine muscle stimulation led to a cervical pressure drop from a mean of 15.8 +/
      6.6 to 5.3 +/- 2.2 cm H2O (P < 0.01). The cervical pressure did not respond to
      stimulation of the anaesthetized uterus. Cervical dilatation caused increase of
      the uterine pressure from a mean of 16.2 +/- 5.2 to 42.8 +/- 10.5 cm H2O (P <
      0.01), whereas cervical stimulation effected a uterine pressure drop to a mean of
      3.6 +/- 1.8 cm H2O (P < 0.01). Stimulation or dilatation of the anaesthetized
      cervix did not cause uterine pressure changes. The invariable cervical dilatation
      upon uterine stimulation suggests a reflex relationship which we have named
      'utero-cervical inhibitory reflex' (UCIR). It seems that the reflex comes into
      action during labour and in conditions of uterine retention of blood or a dead
      ovum. Its impairment may interfere with cervical dilatation or lead to cervical
      incompetence. The UCIR could be included as an investigative tool in utero
      cervical disorders.

PMID- 7714136
TI  - Morphology and ultrastructure of fallopian tube epithelium at different stages of
      the menstrual cycle and menopause.
AB  - The Fallopian tube has been reported to undergo cyclical changes. However, many
      studies of tubal ultrastructure have either examined one segment of the tube only
      or studied animal oviducts. The aim of this study was to document in detail the
      combined morphological and ultrastructural features of the epithelial lining
      along the length of the tube in women at different stages of the menstrual cycle.
      We report an increase in the proportion of ciliated cells along the tube, being
      highest in the fimbriae, but no substantial difference between the follicular and
      luteal phases of the menstrual cycle. In the late follicular phase, fragments of
      cytoplasmic and cellular material were seen in the isthmic lumen but not in the
      outer tubal segments. Similarly, surface domes and secretory granules were more
      prominent in the mid-tube and ampullary sections than in the fimbriae. This
      surface activity was followed by relative quiescence in the early/mid luteal
      phase with reversion to a more active surface but with little secretory activity
      in the late luteal phase. These findings along the Fallopian tube substantiate
      the concept of functional differentiation between the different segments and
      necessitate further studies to determine its clinical relevance.

PMID- 7714137
TI  - A comparative morphological and ultrastructural study of endometrial gland and
      fallopian tube epithelia at different stages of the menstrual cycle and the
      menopause.
AB  - Cyclical ultrastructural changes in the endometrium and Fallopian tube have been
      reported previously but in different subjects. The aim of this study is to
      compare cyclical changes in endometrial gland and tubal (isthmic, mid-tube,
      ampulla, and fimbria) epithelia in the same subjects with a view to identifying
      any similarities or differences which may have clinical implications for assisted
      reproduction treatment. Endometrial and Fallopian tube samples were obtained from
      women undergoing hysterectomy and salpingectomy. We report similar epithelial
      surface changes taking place in the endometrial glandular and endosalpingeal
      epithelia with the exception of the fimbriae. Secretions within endometrial gland
      lumen and the isthmus increase throughout the late follicular phase and before
      ovulation, then dissipate in these two regions simultaneously in the early/mid
      luteal phase. Similarly, in the late follicular and pre-ovulatory phases, the
      process of granule secretion is similar in the glandular epithelium, isthmus and
      ampulla. In the fimbriae, no comparable activity is noted during these phases of
      the menstrual cycle. The differences reflect the functional differentiation
      between these regions. Equally, the observed similarities highlight the need for
      further comparative studies to determine the role of these secretions in early
      embryonic development and their clinical relevance.

PMID- 7714138
TI  - Differential androgen response to adrenocorticotrophin hormone stimulation and
      effect of opioid antagonist on insulin secretion in polycystic ovarian syndrome.
AB  - To investigate the effect of a chronic anti-opioid treatment on the adrenal
      steroid production in polycystic ovarian syndrome (PCOS), 20 women affected by
      PCOS were studied before and after 6 weeks of treatment with an opioid
      antagonist. All women had an oral glucose tolerance test (OGTT) (75 g) on day 5
      of the cycle. At 11.00 p.m. 2 mg of dexamethasone was orally administered and
      blood samples collected the following day at 7.00 a.m. Then 250 micrograms of
      adrenocorticotrophin hormone (ACTH) was injected i.v. and samples collected 60
      min later. At this time a 6 week course of naltrexone treatment (50 mg/day
      orally) was started, following which the protocol was repeated on day 6-7 of the
      menstrual cycle. According to OGTT responses, 10 patients were classified as
      hyperinsulinaemic and 10 as normoinsulinaemic. No difference in baseline hormone
      concentrations was found, except for sex hormone-binding globulin, which was
      significantly greater in normoinsulinaemic patients (P < 0.02). The plasma
      concentration of all steroids after dexamethasone and ACTH administration was
      similar in both groups, except for androstenedione (P < 0.02) and 17 alpha
      hydroxyprogesterone (17-OHP) (P < 0.05), which were significantly greater after
      ACTH injection in hyperinsulinaemic compared with normoinsulinaemic PCOS
      patients. Naltrexone treatment significantly (P < 0.001) reduced insulin response
      to OGTT in the hyperinsulinaemic group, while it did not affect the response in
      the normoinsulinaemic group; thus at the end of the treatment the two groups had
      the same insulin concentrations. Similarly, naltrexone abolished the difference
      between normoinsulinaemic and hyperinsulinaemic patients regarding
      androstenedione and 17-OHP response to ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714139
TI  - Stimulation of ovarian adenylyl cyclase activity by gonadotrophins during the
      natural and gonadotrophin-induced cycles in the hamster.
AB  - In this study we utilized the hamster ovary as a model to investigate the effects
      of ovulation induction with gonadotrophin on the activation of the signal
      transducer effector system, adenylyl cyclase (AC). For this purpose, we prepared
      membrane particles from the ovary and analysed both gonadotrophin-sensitive AC
      and non-receptor-mediated activation during a cycle in which ovulation and
      luteinization were achieved by pregnant mare's serum gonadotrophin (PMSG)/human
      chorionic gonadotrophin (HCG) administration. Results were directly compared with
      AC activation in similarly prepared membranes obtained at different stages of the
      natural unstimulated cycle. AC activity was quantified by the direct conversion
      of ATP substrate into cyclic adenosine monophosphate (cAMP). Measurements of
      ovarian weights, serum oestradiol and progesterone concentrations provided a
      solid base from which to evaluate the functional status of the ovary at each time
      period during the natural and stimulated cycles. We found that ovarian membranes
      contain functional components of the AC system and demonstrated that AC is highly
      dependent on hormonal changes and the functional state of the ovary. Thus, during
      the natural cycle, ovarian AC showed relatively constant responsiveness to
      follicle-stimulating hormone (FSH) throughout the cycle, whereas responsiveness
      to luteinizing hormone (LH)/HCG reached its peak during the luteal phase. On the
      other hand, during the stimulated cycle, sensitivity to FSH and LH/HCG varied
      considerably, being absent during the peri-ovulatory period. AC responsiveness to
      gonadotrophins was only regained 48 h after ovulation. Also during the peri
      ovulatory period of the gonadotrophin-induced cycle, stimulation of ovarian AC
      with non-hormonal activators declines.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714140
TI  - Relationship between ultrasonography and histopathological changes in polycystic
      ovarian syndrome.
AB  - We investigated retrospectively the relationship between the ultrasonographic
      appearance of the ovaries and histopathological findings in patients with
      polycystic ovarian syndrome (PCOS) and compared these histopathological findings
      with endocrine concentrations. A total of 20 patients with PCOS were studied.
      Each patient had a history of infertility, menstrual disturbance and > 10 small
      cysts in each ovary that were detected by transvaginal ultrasound. Ovarian
      ultrasound appearance was classified as a general cystic pattern (GCP) or
      peripheral cystic pattern (PCP). Histological examination of specimens from
      patients undergoing ovarian wedge resection by laparotomy were compared with
      ultrasonographic images. In 15 of the 16 ovaries with GCP, the histopathological
      findings were consistent with the ultrasonographic images. In all 24 ovaries with
      PCP, the histopathological and ultrasonographic images were consistent. The mean
      ovarian capsular thickness was significantly higher in the GCP than the PCP.
      Androstenedione was significantly higher in the GCP than the PCP, whereas the
      ratio of luteinizing hormone to follicle-stimulating hormone was significantly
      higher in the PCP than the GCP. Therefore, our results suggested that GCP and PCP
      correspond to histopathological differences. Histological GCP and PCP appear to
      differ endocrinologically.

PMID- 7714141
TI  - Immunohistochemical localization of growth hormone receptor in cyclic human
      ovaries.
AB  - It has been demonstrated that co-administration of growth hormone (GH) augments
      ovarian response to human menopausal gonadotrophin, and GH itself increases
      steroidogenesis in cultured ovarian cells. It is not clear, however, whether the
      effects of GH on the ovary are direct or not. We performed immunohistochemistry
      using specific monoclonal antibodies against human GH receptor on 51 specimens of
      pre-menopausal human ovaries from various phases of the menstrual cycle to detect
      and localize GH receptors. Immunohistochemical localization of P450 aromatase and
      3 beta-hydroxysteroid dehydrogenase was performed using these enzymes as
      immunohistochemical markers for steroidogenesis in these ovaries. GH receptor
      immunoreactivity was observed in luteinized granulosa cells in corpora lutea in
      the luteal phase, which are considered to be active in steroid production. In the
      follicular phase, GH receptor immunoreactivity was detected in the granulosa
      layer of only three out of 35 antral follicles. These results demonstrate that
      immunoreactivity of GH receptor is present in human ovaries, suggesting a direct
      action of GH on human ovarian functions, especially during luteal phase.

PMID- 7714142
TI  - Oral contraceptives and breast cancer.

PMID- 7714143
TI  - Intravenous immunoglobulin for in-vitro fertilization failure.
AB  - The aim of this study was to determine the effectiveness of intravenous (i.v.)
      immunoglobulin (Ig) for treatment of individuals experiencing failure after in
      vitro fertilization (IVF) and embryo transfer. A total of 29 women with
      unexplained infertility who failed to become pregnant after IVF/embryo transfer
      were divided into two groups based on performance in previous IVF cycles: 16
      women had fertilization of > or = 50% of oocytes retrieved and/or produced > or =
      3 embryos each cycle and 13 had fertilization of < 50% of oocytes retrieved
      and/or produced < 3 embryos each cycle. Each woman had received at least 12
      transferred embryos (95th percentile for successful IVF patients) or had
      experienced two or more biochemical pregnancies without ultrasonic confirmation
      of implantation during previous IVF/embryo transfer attempts. All women received
      i.v. Ig 500 mg/kg prior to the next embryo transfer. Only one of the 13 (8%)
      women with suboptimal fertilization and embryo yield became pregnant in the
      treatment cycle. Of 16 women who had previously had fertilization of at least 50%
      of oocytes retrieved and produced at least three embryos, nine (56%) became
      pregnant in the treatment cycle. The difference in pregnancy rates between the
      two groups is significant (P = 0.02). Intravenous Ig is useful in the treatment
      of unexplained IVF failure in women who have oocyte fertilization rates > or =
      50% and generate at least three embryos per cycle.

PMID- 7714144
TI  - High fecundity rates following in-vitro fertilization and embryo transfer in
      antiphospholipid antibody seropositive women treated with heparin and aspirin.
AB  - This study was undertaken to explore whether intervention with heparin and
      aspirin (H/A) in selected patients undergoing in-vitro fertilization (IVF) and
      embryo transfer could improve fecundity rates. Specifically, it explored the
      possibility that women diagnosed with organic pelvic disease who demonstrated
      antiphospholipid antibodies (APA) could benefit from H/A administration in a
      similar manner to that used in patients with recurrent pregnancy loss. We used an
      enzyme-linked immunosorbent assay for six different phospholipids to identify
      patients who expressed APA before they underwent IVF/embryo transfer. This study
      was confined to the first IVF/embryo transfer cycle that followed assessment of
      APA status and accordingly, the number of IVF/embryo transfer cycles corresponds
      with the number of patients treated. APA seropositive patients were treated with
      aspirin, 81 mg orally q.d., and heparin 5000 IU s.c. b.i.d., beginning on day 1
      of controlled ovarian stimulation. The endpoint for success was a live birth or
      an ultrasound confirming fetal cardiac activity (a viable pregnancy). The
      prevalence of APA in patients diagnosed with organic pelvic disease (53%) was
      much higher than in those without female pathology (14%). The administration of
      H/A to APA seropositive patients significantly (P < 0.05) improved the viable
      pregnancy rate (49%) compared to the untreated APA seropositive group (16%). The
      viable pregnancy rate for APA seropositive women treated with H/A was also
      significantly (P < 0.001) higher than for untreated APA seronegative patients
      (27%). We conclude that all women undergoing IVF/embryo transfer should be tested
      for APA prior to initiating ovarian stimulation and those with APA seropositivity
      should be treated with H/A.

PMID- 7714145
TI  - Is there a role for ovarian stimulation and intra-uterine insemination after age
      40?
AB  - The objective of this study was to determine the conception rate in infertile
      couples in which the female partner was > or = 40 years old and who had received
      ovarian stimulation treatment and intra-uterine insemination (IUI). It was a
      retrospective study of 77 patients who underwent a total of 210 treatment cycles.
      Protocols for ovulation induction included clomiphene citrate, human menopausal
      gonadotrophin (HMG) and clomiphene citrate plus HMG. Patients were monitored
      using transvaginal ultrasound, and two IUI were performed 24 and 48 h after the
      determination of urinary luteinizing hormone (LH) surge or human chorionic
      gonadotrophin (HCG) injection. A total of 11 pregnancies were reported, giving a
      pregnancy rate of 14% per patient and 5% per cycle. Eight spontaneous abortions
      occurred, giving a pregnancy wastage of 73%. In a previous comparative analysis
      of 543 patients < 39 years old receiving IUI and identical protocols of ovarian
      stimulation, 141 pregnancies were achieved, giving a pregnancy rate of 21% per
      patient and 10% per cycle. The miscarriage rate in that group was 18%. This
      report compares IUI results for women > or = 40 years with those obtained
      previously for younger women, and shows the very poor success rate in women > 40
      years of age. This information will be important in the proper counselling of
      this group of patients, as well as indicating that a prompt recommendation for
      assisted reproductive treatment should be made soon after the failure of a few
      attempted cycles of ovarian stimulation treatment and IUI.

PMID- 7714146
TI  - The prognosis for assisted conception treatment after unexpected failure of
      fertilization in vitro: a comparative study.
AB  - The relative prognosis for further assisted conception treatment (without micro
      injection) after initial unexpected failure of fertilization in apparently
      favourable couples undergoing in-vitro fertilization (IVF) treatment was
      assessed. After their first cycle of treatment, 481 consecutive couples were
      grouped according to their fertilization (including cleavage) rate per oocyte
      into five bands. Proportions of couples proceeding to further cycles of treatment
      by IVF or gamete intra-Fallopian transfer (GIFT) and resulting fertilization and
      pregnancy rates were compared. Pregnancy rates in the first cycle of treatment
      were significantly related to fertilization rate. The fertilization rate was zero
      in 13 couples (3%) and only 1-24% in 18 (4%). There were no significant
      differences between these groups in the proportions proceeding to further
      treatment (31, 50%) compared with others (overall 37%, including some treated by
      GIFT), or in their median fertilization rates (75, 60% compared with 67%--IVF
      cycles only), pregnancy rates (20, 38% of cycles compared with 37%--IVF or GIFT)
      or birth rates (20, 38% of cycles compared with 31%--IVF or GIFT). Amongst
      couples whose initial fertilization rate was > or = 50% there was no
      fertilization in 4% of subsequent IVF cycles. We conclude that in couples with
      well defined favourable conditions, including tests of sperm function for
      assisted conception treatment, who have unexpected failure of fertilization, the
      prognosis for further treatment remains favourable without resort to more complex
      investigations or micro-injection methods. Such failure occurs infrequently and
      generally as a random event, and should have no appreciable effect on life-table
      calculation of cumulative pregnancy and birth rates in this group of patients.

PMID- 7714148
TI  - Seasonality in the results of in-vitro fertilization.
AB  - Seasonal variation has been found in various reproductive outcomes. As known
      causes for reducing the rate of success of in-vitro fertilization (IVF) cannot
      explain all the variation in IVF results, we studied whether the season had any
      additional explanatory power. The study population consisted of 1126 women who
      were treated for the first time with IVF at the University Hospital in Nijmegen,
      The Netherlands, between 1987 and 1993. Only first IVF cycles were analysed.
      After adjusting for confounding by the age of the woman, type of infertility,
      indication for IVF and year of aspiration, some seasonal variation was observed
      in the fertilization rate, embryo quality, pregnancy rate and birth rate.

PMID- 7714147
TI  - Composition of commercial gonadotrophin preparations extracted from human post
      menopausal urine: characterization of non-gonadotrophin proteins.
AB  - Gonadotrophin preparations extracted from post-menopausal urine are of low purity
      and the major protein components are not gonadotrophins. A study was undertaken
      to identify some of these non-gonadotrophin proteins present in the extracted
      human urinary gonadotrophin preparations that are commercially available, i.e.
      Humegon (Organon), HMG Massone (Massone), Metrodin (Serono), Metrodin HP
      (Serono), Pergonal (Serono) and Progonadyl (Elea). As revealed by sodium dodecyl
      sulphate polyacrylamide gel electrophoresis (SDS-PAGE) with Coomassie blue
      staining and Western blotting analysis, these products had electrophoretic
      protein profiles which differed in the amounts and species of proteins present.
      With the exception of Metrodin HP, all the other preparations tested contained
      tumour necrosis factor binding protein-I, transferrin, and immunoglobulin-related
      proteins. Some of the products contained in addition: urokinase, Tamm-Horsfall
      glycoprotein and epidermal growth factor. Recently, a highly purified human
      urinary follicle stimulating hormone (FSH) preparation (Metrodin HP) became
      available. In this preparation human FSH represents > 95% of the total proteins
      (approximately 10,000 IU of FSH/mg of protein). Metrodin HP was demonstrated to
      be the purest preparation tested, with none of the above-mentioned contaminants
      detected.

PMID- 7714149
TI  - Infertility evaluation in fertile women: a model for assessing the efficacy of
      infertility testing.
AB  - A standard infertility evaluation consists of a semen analysis,
      hysterosalpingogram, post-coital test, endometrial biopsy and laparoscopy.
      Although these tests are well grounded in clinical experience, information on
      their ability to discriminate between fertile and infertile couples is limited.
      In this study, we performed standard infertility tests plus two others--sperm
      antibodies and cervical culture for Mycoplasma hominis and Ureaplasma urealyticum
      -on fertile and infertile couples. Women in the fertile group were selected from
      those who had delivered a child within the previous 2 years and who were
      scheduled for a laparoscopic tubal ligation. Women in the infertile group were
      selected from those presenting for an infertility evaluation (mean duration of
      infertility 4.2 years), and they were matched by age (+/- 3 years) and race with
      fertile subjects. Subjects were recruited from both private and clinic patients.
      A total of 64 couples (32 matched pairs) completed the evaluation. At least one
      'abnormal' infertility test was found in 69% of fertile and 84% of infertile
      couples. With the exception of tubal damage and endometriosis, which as expected
      were more common in infertile couples, no significant differences between groups
      for remaining infertility factors could be demonstrated. Despite the small size
      of the current study, these results confirm the feasibility and importance of
      comparisons of the prevalence of infertility factors in fertile and infertile
      couples.

PMID- 7714150
TI  - Ovulation induction in the treatment of primary infertility associated with
      unicornuate uterus: report of five cases.
AB  - Five patients with a unicornuate uterus and primary infertility underwent
      ovulation induction with human menopausal gonadotrophins. Four conceived within
      the third cycle of treatment and one spontaneously immediately after the second
      cycle. Ovulation induction appears to be a valid treatment option for primary
      infertility associated with a unicornuate uterus.

PMID- 7714151
TI  - Disturbances of nuclear condensation in human spermatozoa: search for mutations
      in the genes for protamine 1, protamine 2 and transition protein 1.
AB  - During spermiogenesis, the successive replacement of the somatic histones by
      basic proteins, the transition proteins and protamines, allows normal sperm
      nuclear condensation. It was suggested that disturbances in nuclear condensation
      may result in male infertility. Here we report the first molecular analysis of
      the structure of three genes which code for germ cell-specific nuclear proteins,
      namely protamine 1 (PRM1), protamine 2 (PRM2) and transition protein 1 (TNP1) in
      infertile men with disturbed sperm chromatin condensation. In 36 infertile men
      whose spermatozoa showed a positive reaction with aniline blue, which is an
      indication for the presence of histones in the nuclei, the complete nucleotide
      sequences of the coding regions and 5' and 3' untranslated regions of the three
      genes were evaluated. In addition, 10 infertile patients with
      oligoasthenoteratozoospermia were studied in the same way, as well as nine
      infertile patients whose spermatozoa showed a reduction of the protamine 2
      content. We did not detect any mutation in the three genes in any of the
      patients. We assume that the disturbances in the sperm chromatin condensation of
      our patients, and those described in the literature, are not primarily due to
      mutations in the genes for PRM1, PRM2 and TNP1.

PMID- 7714152
TI  - A prospective clinical study of the relationship between the computer-assisted
      assessment of human semen quality and the achievement of pregnancy in vivo.
AB  - The objective of this study was to examine the clinical predictive value for the
      achievement of pregnancy in vivo of the assessment of human semen quality by
      computer-assisted semen analysis using the Hamilton-Thorn Motility Analyser (HTM
      S), alongside classic World Health Organization (WHO) techniques. A prospective
      follow-up study of 303 couples attending a regional infertility clinic providing
      tertiary level services to the population of a single geographical region was
      undertaken. Couples attending the infertility clinic, in whom the female partner
      was normal on conventional investigations (history, examination, evidence of
      ovulation, laparoscopy), were studied. After initial assessment, couples were
      followed for a median of 15 months and treatment-independent pregnancies observed
      and related to the results of semen assessment. During the period of follow-up,
      the treatment-independent pregnancy rate was 52%. Several measures of semen
      quality, determined both manually and by the HTM-S, were found to be predictive
      of the achievement of pregnancy and were related to the time taken to conceive.
      Couples who conceived had higher sperm concentrations and motilities, determined
      both manually and by the HTM-S, as well as differences in sperm head morphometry
      and sperm velocity determined by the HTM-S. Using multiple logistic regression,
      the prognostic accuracy of the HTM-S alone was similar to manual techniques,
      although data from the computer assisted sperm analysis system were preferred.
      Using proportional hazards regression, several variables were related to the
      achievement of pregnancy, particularly morphometry and motility. It was concluded
      that a strong case can be made for the introduction of automated assessment of
      human semen in routine service andrology laboratories.

PMID- 7714153
TI  - Infertile couples with normal counts who require subzonal sperm insertion possess
      a fertility defect that affects zona pellucida penetration.
AB  - The results of subzonal sperm insertion (SUZI) have been retrospectively analysed
      in a subset of patients with normal sperm counts who were found to require SUZI
      because of poor or absent fertilization of zona-intact oocytes. This patient
      group is of particular interest because male factor-related infertility cannot be
      due to insufficient numbers of spermatozoa reaching the oocytes. Thus, failed
      fertilization can be attributed to deficiencies in one or more steps in the
      fertilization process, and SUZI provides a method of distinguishing defects of
      zona pellucida penetration from gamete fusion. A total of 26 such patients were
      treated identically to and concurrently with a much larger group of SUZI
      candidates who typically suffered from oligozoospermia, and fertilization results
      were compared. Fertilization rates after SUZI were higher in patients with normal
      counts than in oligozoospermic patients (51 and 26% respectively), indicating
      that the proportion of spermatozoa capable of fusing with the oocyte is the same
      or higher in the group with normal counts. In addition, nearly all SUZI
      procedures led to fertilization (23/26), with two out of three failed
      fertilizations occurring in cases where two or less oocytes were manipulated,
      results which further indicate that failed fertilization in these patients is not
      due to a defect at the level of gamete fusion. These findings suggest that
      infertility in these patients is based upon the inability of the spermatozoa to
      reach the oolemma and thus, that their fertility defect resides at the step of
      zona penetration.

PMID- 7714154
TI  - Should lysis of adhesions be performed when in-vitro fertilization and embryo
      transfer are available?
AB  - This study was undertaken to report the results of microsurgical lysis of peri
      adnexal adhesions and identify the patients who should be offered surgery and
      those who should be treated by in-vitro fertilization (IVF). In all, 19 women had
      filmy adhesions and 32 had dense adhesions; 68.4% of women with filmy adhesions
      conceived compared with 34.4% of women with dense adhesions (P = 0.02). In
      patients with filmy adhesions, the cumulative pregnancy rate 2 years after
      operation (47%) is similar to that reported after five cycles of IVF (52%),
      leading us to conclude that such patients should be offered surgery first. Dense
      adhesions are best treated by IVF. Lysis of filmy adhesions produces a similar
      intra-uterine pregnancy rate whether performed by laparotomy (57.9%) or
      laparoscopy (56.6%). As operative laparoscopy offers the greatest patient
      comfort, it is the treatment of choice in these patients.

PMID- 7714155
TI  - Long-term follow-up in 206 infertility patients with polycystic ovarian syndrome
      after laparoscopic electrocautery of the ovarian surface.
AB  - In recent publications we have demonstrated that laparoscopic electrocautery of
      the ovarian surface (LEOS) is an effective method to reduce serum androgen
      concentrations, normalizing ovarian cycle length and the ovarian reaction to
      hormonal stimulation therapy in anovulatory patients with polycystic ovarian
      disease (PCOD). In this paper we show that these effects are not only temporary.
      Data from 206 patients undergoing LEOS and monitored for up to 72 months after
      surgery are evaluated; 145 patients achieved a total of 211 conceptions, giving a
      pregnancy rate of 70%, with a maximum of four conceptions in one patient. There
      were 38 early miscarriages (18%) and two late pregnancy losses as well as three
      ectopic implantations.

PMID- 7714156
TI  - Laparoscopic unwinding of adnexal torsion caused by ovarian hyperstimulation.
AB  - A case of laparoscopic unwinding of a twisted enlarged ovary and Fallopian tube
      caused by ovarian hyperstimulation is presented. The laparoscopic unwinding was
      simple and was carried out in a short time. The patient's post-operative course
      was uneventful. Complications such as thromboembolism were not observed and the
      post-operative ovarian function was well preserved after such procedures.
      Preservation of the ovary is highly important in young infertile women. Prompt
      diagnosis with an immediate unwinding of the twisted adnexa by a laparoscopic
      technique can produce a valuable outcome.

PMID- 7714157
TI  - Hysterosalpingography and hysteroscopy in female infertility.
AB  - A total of 323 women of reproductive age (19-40 years) were submitted to a
      complete investigation of infertility routinely including hysterosalpingography
      and hysteroscopy. In 177 cases (54.7%) no pathological conditions were found by
      either of the applied methods, while in 65 cases (20.1%) similar abnormalities
      were observed by hysterosalpingography and hysteroscopy with a global correlation
      of 74.8%. Hysterosalpingography also presented false positive results in 11.7%
      and false negative ones in 13.3% of all the studied cases. In conclusion, the
      combined use of these techniques in infertility investigation gives complete and
      accurate information about the uterine cavity, despite the disadvantages of
      hysterosalpingography due to false positive and false negative results.

PMID- 7714159
TI  - Comparison of pyruvate uptake by embryos derived from conception and non
      conception natural cycles.
AB  - The uptake of pyruvate by human embryos derived from natural cycles in the first
      24 h following fertilization was examined. Since only one egg was obtained and
      therefore only one embryo transferred to the woman, it was possible to relate
      pyruvate consumption by a particular embryo to the outcome of that cycle
      (pregnancy or no pregnancy). The results showed that embryos have a wide range of
      pyruvate uptake values (2-53 pmol/embryo/h) but that this variation was reduced
      significantly to an intermediate range of values in those embryos that were able
      to implant (10-30 pmol/embryo/h). An association was found between embryo
      morphology and pyruvate consumption. Morphologically good embryos were more
      likely to implant if they demonstrated an intermediate pyruvate uptake. However,
      poor embryos did not implant even if they had a pyruvate uptake of 10-30
      pmol/embryo/h. No relationship was found between the type of infertility and
      pyruvate consumption of individual embryos. It is suggested that the ability of
      an embryo to implant is multifactorial and that both morphology and pyruvate
      uptake may be factors.

PMID- 7714158
TI  - A cytosolic sperm factor triggers calcium oscillations and membrane
      hyperpolarizations in human oocytes.
AB  - Intracellular free Ca2+ concentrations ([Ca2+]i) and membrane potentials were
      measured in mature human oocytes. Injection of cytosolic extracts made from human
      or hamster spermatozoa triggered oscillations in [Ca2+]i in human oocytes similar
      to those described previously in mouse and hamster oocytes. In contrast,
      injection of carrier buffer caused no [Ca2+]i increase and injection of Ca(2+)
      containing solutions caused only a single [Ca2+]i transient. Injection of human
      sperm extracts also triggered [Ca2+]i oscillations in mature mouse oocytes. The
      [Ca2+]i oscillations in human oocytes were accompanied by hyperpolarizations in
      membrane potential. Perfusing oocytes with the sulphydryl reagent thimerosal also
      caused oscillations in the free [Ca2+]i concentration simultaneously with
      membrane potential hyperpolarizations. These data suggest that human oocytes
      possess a similar mechanism for generating [Ca2+]i oscillations to those
      described in other mammalian oocytes and a membrane potential response similar to
      that seen previously specifically in hamster oocytes. The data also support the
      view that human oocytes are activated at fertilization by diffusion of a protein
      from the spermatozoa into the ooplasm after gamete membrane fusion.

PMID- 7714160
TI  - Four indications for embryo transfer at the blastocyst stage.
AB  - The transfer of blastocysts obtained by co-culture with 'Vero' (African green
      monkey kidney) cells was offered to infertile couples with the following
      indications: (i) repeated failure of implantation, (ii) patients in whom multiple
      pregnancies had to be avoided (malformed uterus or risk of descending uterus),
      (iii) patients where embryo development potential had to be assessed, and (iv)
      replacement of supernumerary embryos frozen at the blastocyst stage. In the 142
      cycles analysed, the pregnancy rates per transfer were 37.2, 36.3, 13.0 and 13.6%
      respectively for the couples with indications i-iv. The respective implantation
      rates per blastocyst were 20.0, 16.7, 7.1 and 9.3%. In patients in whom multiple
      pregnancies had to be avoided, the transfer of a maximum of two blastocysts gave
      a pregnancy rate per cycle of 23.5%, without any multiple pregnancies. The
      freezing of supernumerary embryos at the blastocyst stage allowed us to replace
      them using simple protocols and to avoid cancellation of the transfer cycles.
      Embryo co-culture has been found to be an interesting technique for selected
      indications, making available a good number of blastocysts for transfer. The
      transfer of blastocysts allowed us to reduce the number of embryos transferred
      per patient and therefore also reduce the rate of multiple pregnancies (there
      were no triplet pregnancies in this study). These results need to be confirmed by
      larger, randomized studies with comparisons to control groups to evaluate the
      effectiveness of blastocyst transfers.

PMID- 7714161
TI  - Ultrastructural analysis of fertilization failure after intracytoplasmic sperm
      injection.
AB  - Human oocytes that failed to display signs of fertilization by 44 h after
      intracytoplasmic sperm injection (ICSI) were processed for electron microscopic
      analysis. All oocytes were arrested at metaphase II. The first polar body
      contained intact cortical granules and chromosome clumps, which were not
      surrounded by a nuclear envelope but still associated with microtubules. When a
      second globular body was present, it always showed the same ultrastructure,
      indicating that it had originated from fragmentation of the first polar body and
      not from the resumption of the second meiotic division. The most prominent
      organelles of the oocyte cytoplasm were the smooth endoplasmic reticulum and
      mitochondria. In the oocyte cortex, cortical granules were intact, with no signs
      of incipient or incomplete cortical reaction. Oocyte chromosomes were found in
      the oocyte periphery near the locality of the first polar body extrusion. They
      consisted of dense aggregates of chromatin associated with microtubules. The
      chromatin of the injected spermatozoon was demembranated and partially
      decondensed. In some cases, vesicular and tubular structures, apparently of
      oocyte origin, were associated with the periphery of the sperm chromatin mass but
      they never formed a continuous layer. These data suggest that fertilization
      failure after ICSI is basically a failure of oocyte activation.

PMID- 7714162
TI  - A retrospective analysis of unfertilized and presumed parthenogentically
      activated human oocytes demonstrates a high frequency of sperm penetration.
AB  - A total of 518 normal-appearing, meiotically mature human oocytes that were
      judged unfertilized after insemination in vitro were examined for sperm
      penetration by conventional fluorescence and laser scanning confocal microscopy
      with DNA-specific probes. A similar analysis was performed on 29 single
      pronuclear oocytes that were presumed to originate by spontaneous
      (parthenogenetic) activation. The results demonstrate that 22% of the
      unfertilized oocytes and 52% of the presumed parthenogenetic oocytes were
      actually penetrated. Sperm penetration occurred in both normozoospermic and male
      factor cases. The findings indicate the importance of penetration analysis in
      determining the causes of fertilization failure that may reside with the male or
      female gamete, especially when assessing the utility of and necessity for
      assisted fertilization in subsequent attempts. The results also suggest that the
      cytoplasmic capacity to decondense sperm DNA may decline more rapidly than the
      ability of the oocyte to be penetrated and to mount an effective block to
      polyspermy.

PMID- 7714163
TI  - The early development and DNA content of activated human oocytes and
      parthenogenetic human embryos.
AB  - A total of 297 human oocytes that had failed to fertilize during in-vitro
      fertilization (IVF) cycles were exposed to the calcium ionophore A23187 to induce
      parthenogenetic activation. Of these oocytes, 192 (65%) activated, the majority
      (63%) exhibiting a single pronucleus and extruding a second polar body. The
      appearance of two pronuclei (18%) was generally associated with a failure to
      extrude the second polar body. Oocytes obtained from patients who were > or = 35
      years had a significantly reduced activation rate (53%). The timing of
      developmental events, such as extrusion of the second polar body, appearance and
      disappearance of pronuclei and the first two cleavage divisions, is broadly
      similar to that seen in fertilized oocytes. However, the developmental potential
      of human parthenogenetic embryos was reduced, as the majority of those allowed to
      continue in culture arrested between the 2-cell and 8-cell stages. Measurements
      of cellular DNA content using a computerized image analysis system showed that
      activated oocytes with one pronucleus had a DNA content compatible with a haploid
      number of chromosomes, while those with two pronuclei were diploid. The ability
      of parthenogenetically activated oocytes to replicate their DNA was also
      demonstrated.

PMID- 7714165
TI  - Ovulation induction and endometrial steroid receptors.
AB  - The endometrial morphology, endometrial steroid receptors and serum steroid
      hormone concentrations have been studied in 22 infertile women participating in
      an in-vitro fertilization, gamete intra-Fallopian transfer programme, including
      nine cases following treatment with gonadotrophin-releasing hormone
      analogue/human menopausal gonadotrophin/human chorionic gonadotrophin. All
      patients had normal ovulatory function before treatment and satisfactory response
      to ovulation induction. Endometrial biopsies were taken in spontaneous and
      treatment cycles on the fourth day after ovulation had been detected by
      ultrasound scanning, when endometrial receptors were measured using
      immunohistochemistry. Histological examination of biopsies in spontaneous cycles
      showed the majority (20/22) to be 'in-phase', while in two cases luteal phase
      defect was diagnosed. After ovulation induction, all the biopsies were still
      morphologically 'in-phase', although a significant reduction had occurred in the
      nuclear receptor level in both the glands and stroma for both progesterone
      receptors (gland P = 0.030, stroma P = 0.012 using microscopic analysis; gland P
      = 0.020, stroma P < 0.001 using a cell analysis system) and oestrogen receptors
      (gland P = 0.017, stroma P = 0.002 using direct microscopic analysis). This
      suggests that a reduction in steroid receptors in the endometrium occurs after
      ovulation induction in the presence of supraphysiological amounts of steroids,
      which is not associated with detectable morphological changes.

PMID- 7714166
TI  - Tumour necrosis factor alpha inhibits in-vitro decidualization of human
      endometrial stromal cells.
AB  - Interleukin-1 (IL-1) has been reported previously to inhibit the in-vitro
      decidualization of human endometrial stromal cells as assessed by progesterone
      induced prolactin production and morphological transformation. In this study we
      examined whether other cytokines, such as tumour necrosis factor-alpha (TNF
      alpha), interferon-beta (IFN beta), IFN gamma or granulocyte-macrophage colony
      stimulating factor (GM-CSF), could affect the decidualization of human
      endometrial stromal cells in vitro. Of these cytokines, TNF alpha significantly
      suppressed prolactin production in a dose-dependent manner, with no apparent
      effect on cell number. The morphological transformation of endometrial stromal
      cells was also inhibited by TNF alpha. TNF alpha and IL-1 significantly
      suppressed cAMP-stimulated prolactin production by endometrial stromal cells.
      Neither the progesterone concentration in the supernatant of the endometrial
      stromal cell culture system nor intracellular calcium concentration of the
      endometrial stromal cells were affected by the addition of TNF alpha or IL-1.
      These results indicated that TNF alpha and IL-1 suppress both progesterone
      induced and cAMP-mediated prolactin production in endometrial stromal cells, and
      that this inhibition was not attributable to direct effects on progesterone
      metabolism or related to Ca(2+)-mediated signal transduction. These experiments
      suggested that a local increase of TNF alpha and IL-1 under certain pathological
      conditions in vivo may disturb blastocyst implantation and/or the maintenance of
      pregnancy by inhibiting the decidualization of endometrial stromal cells.

PMID- 7714164
TI  - Effects of a single post-ovulatory dose of RU486 on endometrial maturation in the
      implantation phase.
AB  - The effect of a single post-ovulatory dose of RU486 on endometrial maturation was
      studied in the implantation phase. A total of 11 healthy women were followed for
      one control and one or two treatment cycles. In treatment cycles, a dose of 200
      or 400 mg RU486 was administered on day luteinizing hormone (LH)+2. In both
      control and treatment cycles, an endometrial biopsy was obtained on LH+6 to LH+8.
      These biopsies were assessed by morphometric and immunohistochemical analyses.
      The treatment with RU486 did not disturb the normal menstrual rhythm but caused a
      significant inhibition in the endometrial development. Glandular progesterone
      receptor staining was significantly more pronounced after RU486 treatment, while
      there was a reduction in the Dolichos biflorus agglutinin lectin binding,
      indicating inhibition of the normal secretory transformation of the endometrium.
      It is likely that these effects on endometrial development and secretory activity
      represent the basis of the contraceptive effect of post-ovulatory RU486
      treatment.

PMID- 7714168
TI  - Very early (24-56 days from last menstrual period) embryonic heart rate in normal
      pregnancies.
AB  - To determine embryonic heart rate in early gestations, 426 ultrasonographic
      examinations from 24 to 56 days from onset of last menstrual period (LMP) were
      studied. All pregnancies had a subsequent successful outcome. Transvaginal
      ultrasonography was performed using an Acuson 128 10XP with a 5 MHz probe.
      Embryonic heart rate was determined by M-mode. No embryonic heart rate was
      observed prior to 34 days of gestation from onset of LMP (n = 65). At 35 days,
      two of 13 (15%) pregnancies had cardiac activity, and by 36 days 16 of 19 (82%)
      pregnancies had cardiac activity. By day 37 from onset of LMP all pregnancies
      demonstrated embryonic cardiac activity. From days 34 to 56, mean embryonic heart
      rate rose from 94 to 166 beats/min. We conclude that embryonic cardiac activity
      is first apparent at day 34 and should be visible by day 37 in normal
      pregnancies.

PMID- 7714167
TI  - The influence of peritoneal fluid from patients with minimal stage or treated
      endometriosis on sperm motility parameters using computer-assisted semen
      analysis.
AB  - The aim of this study was to determine the influence of peritoneal fluid from
      patients with minimal stage or treated endometriosis on sperm motility
      parameters. Peritoneal fluid aspirated at diagnostic laparoscopy for unexplained
      infertility from women during the luteal phase of the menstrual cycle (days 20
      23) was incubated for 5 h with fresh semen samples obtained from men of recently
      proven fertility. Spermatozoa were prepared by a swim-up technique from
      unprocessed semen. Using computer-assisted semen analysis (Hamilton-Thorn
      Research, MA, USA), sperm motility and motion parameters were observed at 0, 120,
      180 and 300 min. Compared with spermatozoa incubated in Earle's balanced salt
      solution/human serum albumin, the percentage motility, percentage progressive
      motility and progressive velocity of spermatozoa incubated in peritoneal fluid
      from patients without visible endometriosis were significantly higher (P < 0.05).
      Maximal effect was observed at 3 h and maintained until 5 h. We conclude that in
      an in-vitro study, in contrast to peritoneal fluid from patients with minimal
      stage endometriosis, peritoneal fluid from patients with unexplained infertility
      and no visible endometriosis can improve sperm motility when compared with
      culture medium.

PMID- 7714169
TI  - Intramural pregnancy following difficult embryo transfer.
AB  - We report an intramural pregnancy following a difficult embryo transfer in a 31
      year-old woman, having in-vitro fertilization and embryo transfer for tubal
      factor infertility. The creation of a 'false passage' at a previous
      instrumentation of the cervix may be implicated in the ectopic placement of
      embryos.

PMID- 7714170
TI  - Serum placental protein 14 concentrations are similar in the first trimester
      pregnancies of women after pituitary down-regulation with a gonadotrophin
      releasing hormone agonist and normal cycles with frozen embryo transfers.
AB  - Previous studies suggest that, in pregnancies after in-vitro fertilization (IVF)
      and embryo transfer following pituitary down-regulation with a gonadotrophin
      releasing hormone analogue (buserelin) and ovulation induction with human
      gonadotrophins, the serum placental protein 14 (PP14) concentration is lower than
      in normally conceived pregnancies. We studied serum PP14 concentrations in two
      groups of women: (i) in 17 infertile women whose pregnancy followed IVF and
      embryo transfer using buserelin (long protocol) and human menopausal
      gonadotrophin for ovulation induction; (ii) in 15 women whose pregnancy followed
      transfer of frozen-thawed embryos. Similar PP14 concentrations were found in both
      groups on days 9-10, 14-15 and 70-77 after human chorionic gonadotrophin
      administration (buserelin, IVF/embryo transfer) or spontaneous luteinizing
      hormone surge (frozen-thawed embryo transfer). Our results show that PP14
      secretion is not compromised by pituitary down-regulation with buserelin in
      infertile women with functional ovaries.

PMID- 7714171
TI  - Comparison of colour Doppler features and pathological findings in complicated
      early pregnancy.
AB  - Resistance index (RI) and pulsatility index (PI) in the uterine and spiral
      arteries, uterine artery peak systolic velocity and intervillous blood flow were
      recorded by transvaginal colour Doppler imaging in 30 missed abortions and 30
      normal pregnancies matched for menstrual age. Pathological examination was
      performed in both groups within 24 h of Doppler investigation. The mean uterine
      PI was significantly (P < 0.01) higher in missed abortions compared to normal
      controls, whereas the mean uterine RI and peak systolic velocity and spiral RI
      and PI did not differ. A continuous intervillous flow was found in 16 out of 23
      (69.6%) of the complicated pregnancies before 12 weeks of gestation whereas it
      was not found in controls. In the missed abortion cases, the trophoblastic shell
      was fragmented or absent in 53% and trophoblastic infiltration and physiological
      changes in the spiral arteries were reduced or absent in 43 and 63%,
      respectively. These findings were not related to normal or abnormal Doppler
      indices. Extended dislocation of the trophoblastic shell and a massive
      infiltration of the intervillous space and placental bed by maternal blood was
      also found in cases presenting with a continuous intervillous blood flow before
      12 weeks of gestation. These findings suggest that abnormal flow velocity
      waveforms in early pregnancies complicated by embryonic death are related to
      deficient placentation and dislocation of the trophoblastic shell that follows
      embryonic demise. The premature entry of maternal blood into the intervillous
      space disrupts the materno-embryonic interface and is probably the final
      mechanism causing abortion.

PMID- 7714172
TI  - Magnetic resonance imaging and transvaginal ultrasound of the uterus prior to
      embryo transfer.
AB  - This study was designed to investigate the role of magnetic resonance (MR)
      imaging in predicting the outcome of in-vitro fertilization (IVF)/embryo transfer
      treatment by seeking differences in receptive compared to unreceptive endometria.
      Women about to undergo embryo transfer were submitted to both vaginal ultrasound
      and MR imaging. Measurements were obtained of the thickness, cross-sectional area
      and volume of uterine layers and of the MR signal intensity ratios between
      layers. Measurements were compared with the occurrence of subsequent successful
      implantation. Although there was no association with either the quantity or the
      relative signal intensity of the endometrium, an interdependence was demonstrated
      between both the endometrium/myometrium and myometrium/junctional zone signal
      intensity ratios and subsequent successful implantation (P < 0.037 and < 0.004
      respectively). It is concluded that MR imaging may provide unique information
      which may help in predicting the outcome of IVF/embryo transfer treatment and in
      understanding implantation. Significant differences were seen in the relative MR
      signal intensities of the myometrium.

PMID- 7714173
TI  - The evolution and outcome of pregnancies from oocyte donation.

PMID- 7714174
TI  - Sperm motility in micro-assisted fertilization.

PMID- 7714175
TI  - Quantification of hepatitis C virus RNA by competitive amplification of RNA from
      denatured serum and hybridization on microtiter plates.
AB  - The direct detection of hepatitis C virus (HCV) RNA by PCR is widely used to
      determine the presence of circulating virions. The most relevant limit of this
      approach is the lack of quantitative information about the viral titer. We report
      a technique of competitive amplification allowing the estimation of HCV RNA copy
      number in biological samples. We constructed a standard competitive RNA template
      containing only two point mutations compared with its wild-type counterpart. The
      competitor was added in titrated amounts to the target RNA, and the mixture was
      then reverse transcribed and amplified in the same reaction tube. The relative
      amounts of target and competitor were determined by differential hybridization on
      microtiter plates with nonradioactive probes. The evaluation of HCV RNA titer
      required a single coamplification with the competitor and could be read from a
      standard curve. Furthermore, this method proved suitable for amplification of HCV
      RNA directly from serum, thus avoiding the intrinsic variability of the RNA
      extraction step.

PMID- 7714177
TI  - Report of six cases of human infection by Serratia plymuthica.
AB  - Serratia plymuthica is an uncommon cause of human infection. Only one case of
      chronic osteomyelitis and two cases of sepsis secondary to central venous
      catheter infection have been documented. We report the isolation of S. plymuthica
      from six patients. The organism was recovered from blood cultures in three cases
      in which the patients had lymphoblastic leukemia, lymphoma, or stroke. Two
      isolates were recovered from exudates (following knee and abdominal surgery). In
      the last case, the organism was isolated from the peritoneal fluid of a patient
      with cholecystitis. The infection was considered nosocomial in five cases and
      community acquired in the other.

PMID- 7714176
TI  - Use of rubella virus E1 fusion proteins for detection of rubella virus
      antibodies.
AB  - Two glutathione S-transferase fusion proteins containing 44 (p1503) and 75
      (p1509) amino acid residues of the rubella virus E1 glycoprotein were expressed
      in Escherichia coli with the aim of producing a recombinant rubella virus antigen
      for use in serological assays. p1503 contained three neutralizing and
      hemagglutinating epitopes (G. M. Terry, L. M. Ho-Terry, P. Londesborough, and K.
      R. Rees, Arch. Virol. 98:189-197, 1988); p1509 contained the putative
      neutralization domain described by Mitchell et al. (L. A. Mitchell, T. Zhang, M.
      Ho, D. Decarie, A. Tingle, M. Zrein, and M. Lacroix, J. Clin. Microbiol. 30:1841
      1847, 1992) in addition to the three epitopes present in p1503. Both fusion
      proteins were soluble and affinity purified on glutathione-Sepharose 4B. In
      Western blots (immunoblots), p1503 and p1509 reacted with human sera containing
      rubella virus-specific immunoglobulin G. When used as antigens in indirect enzyme
      immunoassays to detect rubella virus-specific immunoglobulin G, p1503 correctly
      identified the rubella virus antibody status of 43 (76.8%) and p1509 correctly
      identified that of 48 (85.7%) of 56 serum samples received for routine rubella
      virus antibody screening. The results obtained with p1509 compare well with those
      obtained with a latex agglutination assay.

PMID- 7714178
TI  - Detection and subsequent sequencing of Puumala virus from human specimens by PCR.
AB  - A sensitive method based on PCR was developed for the detection of Puumala virus
      (PUU) in human samples. The assay was found to be specific for PUU-like strains
      and distinguished between these and hantaviruses of other serotypes. The
      detection limit was found to be 10(-5) focus-forming units. Clinical samples were
      collected from patients with nephropathia epidemica in Sweden and western Russia.
      Five whole blood samples collected from patients in Russia with the acute phase
      of disease were found to be positive by the PCR. All samples were negative for
      PUU antigen when examined by enzyme-linked immunosorbent assay. Virus isolation
      on Vero E6 cells from several of the acute-phase samples, including the 5 PCR
      positive samples, was not successful. The amplified samples were subjected to
      direct nucleic acid sequencing for confirmation of identity. The sequences
      differed from each other and were closely related to the Russian bank vole
      isolate CG-1820, thereby indicating the origin of nephropathia epidemica. The PCR
      was used for amplification and subsequent nucleotide sequencing of eight PUU-like
      isolates with different geographic origins. The Swedish strains were more closely
      related to the Finnish PUU prototype strain, Sotkamo, than to the Russian
      isolates. Interestingly, a Belgian isolate, CG-13891, differed markedly from all
      other PUU strains.

PMID- 7714179
TI  - Solid-phase C1q-directed bacterial capture followed by PCR for detection of
      Chlamydia trachomatis in clinical specimens.
AB  - An antigen capture system based on the binding of bacteria to solid-phase
      immobilized complement C1q followed by PCR for detection of Chlamydia trachomatis
      in clinical samples was developed and clinically evaluated. Comparison of C1q
      directed antigen capture PCR with cell culture and direct PCR on 71 consecutive
      clinical specimens revealed an identical sensitivity. In this group, all 11 cell
      culture-positive samples were positive by direct PCR and C1q-directed antigen
      capture PCR. In addition, two samples found negative by cell culture were found
      positive by both direct PCR and C1q-directed antigen capture PCR. To further
      assess the sensitivity of C1q-directed antigen capture PCR, 20 clinical samples
      with one to five inclusions in cell culture and 20 clinical samples with 6 to 20
      inclusions in cell culture were tested. Results obtained showed sensitivities of
      95 and 90% for clinical samples with 6 to 20 and 1 to 5 inclusions in cell
      culture, respectively. Using C1q-coated solid phases, C1q-binding Chlamydia
      particles can be concentrated from large volumes with concomitant removal of
      inhibitors of PCR, allowing the use of large volumes of clinical samples for
      clinical testing. Since C1q has been shown to bind to a range of gram-negative
      bacteria, the newly developed technique has utility for a broad range of
      bacteria.

PMID- 7714181
TI  - Human cord blood mononuclear cells are preferentially infected by non-syncytium
      inducing, macrophage-tropic human immunodeficiency virus type 1 isolates.
AB  - Identification of the factors which impact on the transmission of human
      immunodeficiency virus type 1 (HIV-1) from an infected mother to her infant is
      essential for the development of effective strategies to prevent perinatal HIV-1
      infection. The current study was designed to determine if unstimulated human
      neonatal cord blood mononuclear cells (CBMC) differ from adult peripheral blood
      mononuclear cells (PBMC) in susceptibility to HIV-1 infection. Both cell
      populations were challenged with two laboratory and two clinical HIV-1 isolates
      with different phenotypic properties. Infection was evaluated by quantitation of
      p24 antigen production and p24 antigen expression by an enzyme immunoassay and
      immunofluorescence, respectively. T-cell markers were determined by flow
      cytometry. Unstimulated CBMC were preferentially infected by macrophage-tropic,
      non-syncytium-inducing (non-SI) laboratory and clinical isolates, whereas PBMC
      were more susceptible to T-lymphotropic, SI HIV-1 strains. The macrophage-tropic
      strain HIV-1Ba-L replicated to 100-fold higher titers in CBMC than a similar
      inoculum of the SI isolate HIV-1LAI. The opposite occurred in unstimulated PBMC,
      which replicated HIVLAI to eightfold higher titers than the macrophage-tropic
      isolate. These findings indicate that a selection of viral phenotype may occur
      with unstimulated CBMC displaying a predominant susceptibility to infection by
      macrophage-tropic, non-SI HIV-1 strains and that this selection may influence
      mother-infant transmission of HIV-1.

PMID- 7714180
TI  - Rapid detection of bovine viral diarrhea virus by using RNA extracted directly
      from assorted specimens and a one-tube reverse transcription PCR assay.
AB  - We describe a simple method for the rapid detection of bovine viral diarrhea
      virus (BVDV) that uses a one-tube reverse transcription PCR (RT-PCR) and total
      RNA extracted directly from a variety of bovine specimens, including whole blood
      and tissues. Reagents for both RT and PCR were combined in a one-tube, single
      buffer system, and amplification was performed with a single uninterrupted
      thermal cycling program. Using the novel cationic surfactant
      tetradecyltrimethylammonium oxalate (Catrimox-14), we consistently extracted RT
      PCR-quality RNA from specimens containing blood. Amplification with primers
      derived from conserved sequences within the BVDV 5'-untranslated region yielded a
      244-bp product. Assay specificity was confirmed by ethidium bromide-stained gel
      electrophoresis and by chemiluminescence-assayed Southern blot hybridizations
      involving BVDV 5'-untranslated region-specific digoxigenin-labelled cDNA probes.
      The assay detection level was 0.1 50% tissue culture infectious dose of BVDV when
      ethidium bromide-stained gel electrophoresis was used and 0.01 50% tissue culture
      infectious dose of BVDV when Southern blot hybridization was used. Our method is
      an alternative to the conventional cell culture assays used in a diagnostic
      laboratory and is an improvement over existing RT-PCR assays for BVDV.

PMID- 7714184
TI  - Excretion of bovine herpesvirus 1 in semen is detected much longer by PCR than by
      virus isolation.
AB  - To compare the sensitivities of PCR and virus isolation and to examine the course
      of virus excretion in semen, we intrapreputially inoculated eight bulls with
      bovine herpesvirus 1 (BHV1) and used two bulls as sentinels. From these bulls, we
      collected a large panel of semen samples during 65 days postinfection (dpi). At
      44 dpi the bulls received dexamethasone to reactivate putatively latent virus. We
      analyzed the semen samples by virus isolation on egg yolk-extended semen (VIE
      test), by virus isolation on fresh semen (VIF test), and by a PCR test on egg
      yolk-extended semen. Of the 162 semen samples that were collected, the VIE test
      scored 24 positive, the VIF test scored 51 positive, and the PCR test scored 118
      positive. At 6 dpi all samples from the inoculated bulls were found to be
      positive by all three tests. From 9 to 44 dpi most samples were found to be
      negative by both virus isolation tests but positive by the PCR test. From 48 to
      55 dpi the dexamethasone treatment induced virus reactivation, which was
      evidenced by an increase in the number of positive VIE, VIF, or PCR tests. From
      58 to 65 dpi all samples were found to be negative in both virus isolation tests,
      but several samples were still found to be positive by the PCR test. To determine
      whether BHV1 DNA was present in the dorsal root ganglia of the infected bulls, we
      analyzed by PCR several thoracic, lumbar, and sacral ganglia collected at 65 dpi.
      BHV1 DNA was frequently present in the third, fourth, and fifth sacral ganglia,
      and semiquantitative PCR analysis showed that the highest amounts of BHV1 DNA (10
      to 30 molecules of BHV1 DNA per 10(5) cells) were present in the third sacral
      ganglion, The results demonstrate that the PCR test detected five times as many
      positive semen samples as the VIE test. Hence, intrapreputially infected bulls
      excrete BHV1 in semen much longer than recognized until now.

PMID- 7714183
TI  - A novel insertion element from Mycobacterium avium, IS1245, is a specific target
      for analysis of strain relatedness.
AB  - The insertion sequence IS1245 is a novel mycobacterial repetitive element
      identified in Mycobacterium avium. It encodes a transposase which exhibits a 64%
      amino acid similarity with IS1081, an insertion element present in the M.
      tuberculosis complex. The host range of IS1245 appears limited to M. avium as
      this element was not identified in M. intracellulare or in any other of 18
      mycobacteria species tested. When IS1245 was used for restriction fragment length
      polymorphism (RFLP) analysis, human isolates characteristically presented a high
      number of copies (median, 16; range, 3 to 27) and a diversity of RFLP patterns
      comparable to that found by pulsed-field gel electrophoresis. Isolates from
      nonhuman sources differed both in number of copies and in RFLP pattern diversity:
      while swine isolates shared the characteristics of human strains, those from
      several avian sources exhibited a very low copy number of IS1245 and appeared
      clonal on the basis of RFLP.

PMID- 7714185
TI  - Comparison of BacT/Alert with Signal blood culture system.
AB  - The BacT/Alert (Organon Teknika Corp., Durham, N.C.) is an automated blood
      culture system. It is based on the detection of CO2 by means of a colorimetric
      sensor internally attached to the bottom of culture bottles. The aerobic and
      anaerobic media of this system were compared with one bottle of the Signal system
      (Oxoid Ltd., Hampshire, United Kingdom). At bedside, 20 ml of blood was drawn
      from each adult patient. The two BacT/Alert bottles were inoculated with 5 ml of
      blood each; the Signal bottle was inoculated with 10 ml. A total of 5,284 sets
      (2,483 patients; 2.1 cultures per patient) consisting of three bottles each were
      evaluated, of which 781 sets (14.8%) revealed microorganisms (n = 892); 642 of
      these were considered to be pathogenic. Significantly more (P < 0.0001) pathogens
      were isolated from the two BacT/Alert bottles together (n = 584) than from the
      single Signal bottle (n = 515). Escherichia coli (P = 0.007), gram-negative
      bacteria other than members of the family Enterobacteriaceae or Pseudomonas spp.
      (P = 0.006), and yeasts (P = 0.02) were isolated more often from both or either
      BacT/Alert bottle. Comparing the systems in terms of 388 different organisms per
      septic episode, the difference between BacT/Alert and Signal was significant for
      the total number of septicemia cases (P = 0.003). More contaminants grew in the
      BacT/Alert system (173 versus 116; P = 0.0001). False-positive indications were
      more frequent in the BacT/Alert system, 198 (3.7%) aerobic bottles and 57 (1.1%)
      anaerobic bottles, than in the Signal bottles, 24 (0.5%) bottles. Pathogens could
      be detected significantly earlier (P < 0.0001) in the BacT/Alert system than in
      the Signal system. The BacT/Alert instrument with two bottles allowed earlier
      detection as well as the isolation of more microorganisms than the manual, one
      bottle Signal system.

PMID- 7714182
TI  - Measurement of human immunodeficiency virus type 1 p24 in serum by an
      ultrasensitive enzyme immunoassay, the two-site immune complex transfer enzyme
      immunoassay.
AB  - Human immunodeficiency virus type 1 (HIV-1) p24 antigen was measured by an
      ultrasensitive enzyme immunoassay (two-site immune complex transfer enzyme
      immunoassay). The antigen was reacted simultaneously with 2,4-dinitrophenyl
      biotinyl-bovine serum albumin-anti-recombinant p24 (rp24) Fab' conjugate and anti
      rp24 Fab'-beta-D-galactosidase conjugate. The complex that was formed, comprising
      the three components, was transferred from polystyrene beads coated with affinity
      purified (anti-2,4-dinitrophenyl group) immunoglobulin G (IgG) to polystyrene
      beads coated with streptavidin. The detection limit of rp24 was 2.4 fg (0.1 amol)
      per assay or 0.24 pg/ml with as little as 10 microliters of serum. When sera were
      treated at low pH, p24 was detected in 34 (68%) of 50 serum samples from
      asymptomatic carriers, in 25 (86%) of 29 serum samples from patients with
      advanced HIV-1 infection, and in none of 117 serum samples from HIV-1
      seronegative individuals. Levels of p24 in serum were inversely correlated to
      those of anti-HIV-1 p24 IgG, and the recovery of rp24 added to serum decreased to
      zero with increasing levels of anti-HIV-1 p24 IgG in serum. This sensitive method
      may be used as a powerful tool for investigating the disease.

PMID- 7714186
TI  - Type- and subtype-specific detection of influenza viruses in clinical specimens
      by rapid culture assay.
AB  - A rapid culture assay which allows for the simultaneous typing and subtyping of
      currently circulating influenza A(H1N1), A(H3N2), and B viruses in clinical
      specimens was developed. Pools of monoclonal antibodies (MAbs) against influenza
      A and B viruses and MAbs HA1-71 and HA2-76, obtained by immunizing mice with the
      denatured hemagglutinin subfragments HA1 and HA2 of influenza virus
      A/Victoria/3/75, were used for immunoperoxidase staining of antigens in infected
      MDCK cells. MAb HA1-71 reacted exclusively with influenza A viruses of the H3
      subtype, while MAb HA2-76 reacted with subtypes H1, H3, H4, H6, H8, H9, H10, H11,
      and H12, as determined with 78 human, 4 swine, and 10 avian influenza virus
      reference strains subtyped by the hemagglutination inhibition test. To determine
      if the technique can be used as a rapid diagnostic test, 263 known influenza
      virus-positive frozen nasal or throat swabs were inoculated into MDCK cells.
      After an overnight incubation, the cells were fixed and viral antigens were
      detected by immunoperoxidase staining. Influenza A viruses of the H1 and H3
      subtypes were detected in 31 and 113 specimens, respectively. The subtypes of 10
      influenza A virus-positive specimens could not be determined because they
      contained too little virus. Influenza B viruses were detected in 84 specimens,
      and 25 specimens were negative. We conclude that this assay is a rapid,
      convenient, non-labor-intensive, and relatively inexpensive test for detecting,
      typing, and subtyping influenza viruses in clinical specimens.

PMID- 7714187
TI  - Evaluation of API An-IDENT and RapID ANA II systems for identification of
      Actinomyces species from clinical specimens.
AB  - We compared the accuracy of the An-IDENT system (bioMerieux Vitek, Inc.,
      Hazelwood, Mo.) and the RapID ANA II system (Innovative Diagnostic Systems,
      Norcross, Ga.) with that of conventional biochemical tests for the identification
      of 85 strains of Actinomyces species. In our hands, the overall accuracy of the
      An-IDENT was 59% and that of the RapID ANA II was 24%. The error rate for the An
      IDENT was 18% and that for the RapID ANA II was 38%. The results of this study
      suggest that although the An-IDENT was more accurate than the RapID ANA II (P <
      0.005), neither system, in our hands, was able to identify Actinomyces species
      with an acceptable degree of accuracy. It is recommended that suspected
      Actinomyces isolates be identified by conventional testing.

PMID- 7714188
TI  - Proposed quality control guidelines for antimicrobial susceptibility tests using
      tilmicosin.
AB  - Quality control guidelines for tilmicosin, a novel veterinary-use-only macrolide,
      were developed in a multi-laboratory study according to established National
      Committee for Clinical Laboratory Standards (NCCLS) procedures (M23-T2).
      Tilmicosin was incorporated into Sensititre plates for broth microdilution
      endpoint testing and into two lots of 15-micrograms disks for Kirby-Bauer agar
      disk diffusion testing. One common lot and five unique lots of Mueller-Hinton
      media were used. (Broth was cation adjusted, and agar was supplemented with 5%
      defibrinated sheep blood.) Bacteria used for reference strains included
      Pasteurella haemolytica 128K, Pasteurella multocida ATCC 43137, and
      Staphylococcus aureus ATCC 29213 (microdilution) and ATCC 25923 (disk). Replicate
      tests were conducted. Disk diffusion and broth microdilution quality control
      ranges are proposed.

PMID- 7714189
TI  - Detection of Yersinia pestis fraction 1 antigen with a fiber optic biosensor.
AB  - A fiber optic biosensor was used to detect the fraction 1 (F1) antigen from
      Yersinia pestis, the etiologic agent of plague. The instrument employs an argon
      ion laser (514 nm) to launch light into a long-clad fiber and measures the
      fluorescence produced by an immunofluorescent complex formed in the evanescent
      wave region. This sensing area is a short section (12.5 cm) at the end of the
      optical fiber from which the cladding has been removed and in which the silica
      core has been tapered. Capture antibodies, which bind to F1 antigen, were
      immobilized on the core surface to form the basis of the sandwich
      fluoroimmunoassay. The ability to detect bound F1 antigen was provided by adding
      tetramethylrhodamine-labeled anti-plaque antibody to form fluorescent complexes.
      The evanescent wave has a limited penetration depth (< 1 lambda), which restricts
      detection of the fluorescent complexes bound to the fiber's surface. The direct
      correlation between the F1 antigen concentration and the signal provided an
      effective method for sample quantitation. This method achieved a high level of
      accuracy for determining F1 antigen concentrations from 50 to 400 ng/ml in
      phosphate-buffered saline, serum, plasma, and whole blood, with a 5-ng/ml limit
      of detection. Subsequent blind studies, which included serum samples from
      patients, yielded results in good agreement with measurements by enzyme-linked
      immunosorbent assay. A major advantage of the fiber optic biosensor is that
      results can be generated within minutes while isolating the user from hazardous
      samples. These factors favor development of this biosensor into a facile and
      rapid diagnostic device.

PMID- 7714190
TI  - Specific, sensitive, and rapid assay for human immunodeficiency virus type 1 pol
      mutations associated with resistance to zidovudine and didanosine.
AB  - The effectiveness of antiretroviral therapy may be limited by the development of
      human immunodeficiency virus type 1 (HIV-1) resistance. Monitoring for resistance
      will perhaps allow changes in therapy prior to deterioration in the patient's
      clinical or immunologic status. Our objective was to develop a rapid, specific,
      and sensitive genotypic assay for HIV-1 resistance to zidovudine (ZDV) and
      didanosine (ddI) which is simple to perform. In our assay the DNA of HIV-1 pol
      was amplified by PCR using two sets of nested oligonucleotide primers. Mutations
      of reverse transcriptase (RT) encoding amino acids (aa) 74 and 41, 70, and 215
      which have been associated with HIV-1 resistance to ddI and ZDV, respectively,
      were detected with a ligase detection reaction (LDR) and indicated
      colorimetrically. The RT genotypes of 35 patient specimens (140 codons) blindly
      assessed for these mutations were in agreement by PCR-LDR and by
      dideoxynucleotide sequencing. To evaluate the limits of the assay, other
      specimens with mutations close to the ligation site were evaluated by PCR-LDR.
      The assay was sensitive and specific for all specimens except when mutations
      occurred within 2 bases on either side of the ligation site. In summary, this PCR
      LDR assay specifically, sensitively, and rapidly detected pol mutations (RT aa
      74, 41, 70, and 215) associated with HIV-1 resistance to ddI and ZDV.

PMID- 7714191
TI  - Enzyme-linked immunosorbent assay for detecting antibodies to Borna disease virus
      specific proteins.
AB  - Borna disease virus is a unique neurotropic RNA virus that causes neurologic
      disease in a wide variety of animal hosts. We established an enzyme-linked
      immunosorbent assay for the detection of antibodies to Borna disease virus on the
      basis of the use of three recombinant viral proteins (recp40, recp23, and
      recp18). This assay system is more sensitive and rapid than the methods currently
      used for the serologic diagnosis of infection such as Western blotting
      (immunoblotting), indirect immunofluorescence test, or immunoprecipitation.

PMID- 7714193
TI  - Comparison of Crystal Enteric/Nonfermenter system, API 20E system, and Vitek
      AutoMicrobic system for identification of gram-negative bacilli.
AB  - A comparative evaluation of the Crystal Enteric/Nonfermenter system (Crystal;
      Becton Dickinson, Cockeysville, Md.), API 20E (API; bioMerieux Vitek, Inc.,
      Hazelwood, Mo.), and the Vitek GNI card (Vitek; bioMerieux Vitek) was performed
      with 512 clinical isolates of gram-negative bacilli, including 381 members of the
      family Enterobacteriaceae and 131 nonenteric bacilli. With supplemental testing,
      API, Crystal, and Vitek correctly identified to the genus and species level 505
      (98.6%), 489 (95.5%), and 494 (96.5%) of the 512 isolates, respectively.
      Supplemental testing, as specified by the manufacturer, was required to identify
      119 (23.2%), 18 (3.5%), and 5 (1.0%) of the isolates with the three systems,
      respectively. Of the 381 isolates from the family Enterobacteriaceae, API and
      Crystal correctly identified 90.3 and 91.6% by 18 to 24 h without supplemental
      testing, respectively, and Vitek identified 92.4 and 96.1% following 10 and 18 h
      of incubation, respectively. Of the 131 nonenteric organisms, API and Crystal
      correctly identified 28.2 and 93.9% by 18 to 24 h without supplemental testing,
      respectively, and Vitek identified 84.0% by 10 h and 93.9% by 18 h. Errors in
      identification with each system were infrequent and appeared to be randomly
      distributed among the genera evaluated. The three systems were comparable in
      accuracy when either a weighted clinical laboratory profile of organisms or a
      group of selected isolates in a stress test sample was evaluated (P > 0.05).
      There were no significant differences between the three systems in their ability
      to identify either the isolates in the weighted group or those in the stress test
      (P > 0.05). Crystal compared favorably with API and Vitek, which have established
      track records in clinical laboratories, and is acceptable for the identification
      of members of the Enterobacteriaceae and nonenteric bacilli in a clinical
      microbiology laboratory.

PMID- 7714192
TI  - M or M-like protein gene polymorphisms in human group G streptococci.
AB  - Many group G streptococci (GGS) isolated from infected humans (but not from
      animal sources) express M or M-like proteins with biological, immunochemical, and
      genetic features similar to those of group A streptococci (GAS). To further
      elucidate the recently proposed M-like protein gene (emmL gene) polymorphisms in
      GGS, Southern blots of genomic DNAs from 38 epidemiologically unrelated GGS
      strains isolated from human specimens and 12 GGS strains recovered from animal
      sources were hybridized with oligonucleotide probes designed to specifically
      detect GAS M class I and M class II M protein (emm) genes. All human-associated
      GGS strains showed DNA homology to the GAS M class I emm gene probe, whereas no
      hybridization was found with DNA from any of the animal-associated strains. The
      emmL genes from all human isolates were amplified by PCR, and the complete
      sequence of the emmL gene of the Rebecca Lancefield grouping strain D166B was
      determined. Again, this gene exhibited the structural features typical for emm
      genes of M class I GAS. The 5' regions of the PCR-amplified emmL genes of the
      remaining 37 human GGS strains were sequenced. This region showed a sequence
      diversity similar to that known for GAS emm genes. When strains whose N-terminal
      emmL gene sequences showed a homology of > 95% were defined as belonging to one
      genetic type, 30 strains were segregated into six distinct genetic types, whereas
      the remaining 8 strains each exhibited a unique emmL gene sequence. A high degree
      of homology between the N-terminal emmL gene segments of six GGS strains and the
      corresponding regions of either the emm12 or the emm57 gene of GAS was found,
      suggesting a horizontal gene transfer between strains of these species of beta
      hemolytic streptococci. Besides a further understanding of the evolution of GGS
      emmL genes, the observed emmL gene polymorphisms in GGS could provide the basis
      for a molecular subspecies delineation of strains and offers the potential of
      typing GGS for epidemiological purposes.

PMID- 7714194
TI  - Effects of select medium supplements on in vitro development of Cryptosporidium
      parvum in HCT-8 cells.
AB  - Surface-sterilized oocysts of Cryptosporidium parvum were applied to subconfluent
      monolayers of human adenocarcinoma (HCT-8) cells grown on coverslips in six-well
      cluster plates. Parasite-infected cultures were then incubated in RPMI 1640 with
      10% fetal bovine serum, 15 mM HEPES (N-2-hydroxyethylpiperazine-N'-2
      ethanesulfonic acid) buffer, and antibiotics at 37 degrees C in a 5% CO2-95% air
      incubator for 2 h to allow sporozoites to excyst and enter cells. After cultures
      were washed free of debris, fresh cell culture media containing select
      supplements were added and cultures were reincubated. Parasite growth was
      assessed 66 h later by counting the number of parasite developmental stages in 25
      random x 100 oil fields by Nomarski interference-contrast microscopy. Four
      vitamin supplements, calcium pantothenate, L-ascorbic acid, folic acid, and 4
      (para)-aminobenzoic acid, each resulted in a significant increase in parasite
      numbers in vitro. The addition of insulin and the sugars glucose, galactose, and
      maltose also had a positive effect on parasite growth, although the effect was
      less pronounced than with any of the vitamins. Using the above information, we
      developed a supplemental medium formulation consisting of RPMI 1640 with 10%
      fetal bovine serum, 15 mM HEPES, 50 mM glucose, and 35 micrograms of ascorbic
      acid, 1.0 micrograms of folic acid, 4.0 micrograms of 4-aminobenzoic acid, 2.0
      micrograms of calcium pantothenate, 0.1 U of insulin, 100 U of penicillin G, 100
      micrograms of streptomycin, and 0.25 microgram of amphotericin B (Fungizone) per
      ml (pH 7.4). The growth of c. parvum in this medium was found to be enhanced
      approximately 10-fold compared with that in control medium without additional
      glucose, insulin, or vitamins.

PMID- 7714196
TI  - Identification of Helicobacter pylori by immunological dot blot method based on
      reaction of a species-specific monoclonal antibody with a surface-exposed
      protein.
AB  - Monoclonal antibodies (MAbs) against membrane preparations of Helicobacter pylori
      were produced. One MAb was found to be specific for H. pylori, because it did not
      react with a number of other bacterial species, including Helicobacter felis and
      Campylobacter jejuni. This MAb reacted with a 30-kDa protein found in outer
      membrane preparations of H. pylori. The protein was also detected on the cell
      surface on intact bacteria when analyzed by immunoelectron microscopy. To
      facilitate the identification of H. pylori isolates after culturing of biopsies,
      an immunodot blot assay based on the reaction of this MAb was developed. This
      assay was found to be highly specific for H. pylori. Sixty-six clinical isolates
      typed as H. pylori by conventional biochemical tests were found to be positive,
      whereas no other bacterial species tested gave a positive result. By this method,
      reliable and rapid identification of H. pylori could be accomplished.

PMID- 7714195
TI  - Molecular population genetic analysis of Staphylococcus aureus recovered from
      cows.
AB  - Staphylococcus aureus is one of the most common causes of bovine mastitis. To
      estimate genetic relationships among S. aureus strains recovered from cows, 357
      isolates from milk samples from worldwide localities were examined for
      electrophoretic variation at 13 metabolic-enzyme loci. Thirty-nine
      electrophoretic types which represented distinctive multilocus enzyme genotypes
      were identified, and nearly 90% of all isolates were assigned to one of eight
      clones. Genetic heterogeneity was found among organisms recovered from dairy
      herds from which multiple isolates were obtained, indicating that the S. aureus
      population in a single herd can be multiclonal. Although humans and cows shared 7
      of the 39 S. aureus clones, each clone was predominantly associated with one of
      these host species. These results are consistent with the concept of host
      specialization among S. aureus clones and imply that successful transfer of
      bacteria between humans and cows is limited.

PMID- 7714197
TI  - Identification of Streptococcus porcinus from human sources.
AB  - Streptococcus porcinus is normally associated with infections in swine. Cultures
      of this streptococcal species are rarely reported from human infections. In the
      past 10 years, we have identified 13 cultures of S. porcinus from human sources
      from persons living in the United States and Canada. Seven of the strains were
      identified in the past 15 months. Nine of the strains were of a single serogroup,
      provisionally called C1. In addition, nine of the strains were isolated from the
      genitourinary tract of reproductive-age female patients, some with delivery
      problems. S. porcinus strains could be identified by hemolytic, serologic, and
      physiologic characteristics. All strains were susceptible to penicillin,
      erythromycin, and other antimicrobial agents. Fifty-four percent of the strains
      were resistant to tetracycline. These findings suggest that we may be seeing a
      change in the flora of the genitourinary tract of humans. Whether these isolates
      are significant pathogens is unknown at this time.

PMID- 7714198
TI  - Monitoring levels of human cytomegalovirus DNA in blood after liver
      transplantation.
AB  - We evaluated a semiquantitative PCR assay prospectively in 40 liver transplant
      recipients as an aid in making a prompt diagnosis of cytomegalovirus (CMV)
      infection. For 2 months after transplantation, clinical specimens from patients
      were tested weekly by PCR, virus isolation from peripheral blood and urine, and
      CMV serology. The incidence of active CMV infection was 70%. The levels of CMV
      DNA determined by hybridization of PCR samples and densitometric scanning of
      blots were assigned a score of 1 to 4 by comparison with four external standards
      amplified in parallel and corresponding to a range of 80 to 80,000 genomes. The
      first detection of CMV in blood by PCR occurred at a mean of 15 days, and high
      level PCR scores of 3 or 4 were obtained 21 days after transplantation, whereas
      viremia occurred 33 days after transplantation. Significantly higher levels of
      CMV DNA were seen in patients with CMV disease (P < 0.05) than in asymptomatic
      patients. The prevalence of symptomatic CMV infection was 30%. The positive
      predictive value of PCR was 48%, while the negative predictive value was 100%.
      After treatment, the clearance of CMV DNA was always observed and the
      disappearance of symptoms occurred concomitantly with undetectable PCR signals.

PMID- 7714200
TI  - Mycobacterial testing in clinical laboratories that participate in the College of
      American Pathologists' Mycobacteriology E survey: results of a 1993
      questionnaire.
AB  - Participants in the College of American Pathologists' Mycobacteriology E
      proficiency testing survey in 1993 were asked to complete a questionnaire
      addressing mycobacterial test methods, test volume, and frequency of detection of
      drug-resistant Mycobacterium tuberculosis (MTB). A similar questionnaire had been
      distributed in 1992. The population responding to the 1993 questionnaire changed,
      because of a shift of small hospitals to the limited Mycobacteriology E1 survey,
      and the format of some questions was altered, so a direct comparison of 1992 and
      1993 responses was not always possible. Among participants who answered the
      questions in both years, there was a significant increase in the use of the
      fluorochrome stain (57% in 1992, 61% in 1993), BACTEC TB for culture (34% in
      1992, 38% in 1993) and susceptibility testing (51% in 1992, 61% in 1993), and DNA
      probes for identification (30% in 1992, 51% in 1993). The percentage of
      participants who processed respiratory specimens at least seven times per week
      increased from 9% in 1992 to 13% in 1993, and the percentage processing five
      times per week increased from 68 to 72%. The percentage of respondents who
      reported an identification of MTB within 21 days of specimen receipts and
      susceptibility test results within 28 days in 1992 and 1993 increased from 30 to
      41% and from 12 to 19%, respectively. In regard to resistant MTB, 177
      institutions in 1991 and 291 in 1992 reported resistance to isoniazid, and 114 in
      1991 and 187 in 1992 reported resistance to both isoniazid and rifampin.
      Laboratorians are to be applauded for using the more rapid mycobacterial testing
      methods; however, given that tuberculosis remains a problem, this trend must
      continue.

PMID- 7714199
TI  - Evidence for absence in northern Europe of especially virulent clonal types of
      Actinobacillus actinomycetemcomitans.
AB  - Genetic analysis of an Actinobacillus actinomycetemcomitans population consisting
      of 88 clinically well characterized Finnish isolates performed by multilocus
      enzyme electrophoresis confirmed that the five serotypes divide into two
      phylogenetic lineages, one comprising serotypes b and c and one comprising
      serotypes a, d, and e. There was no association between any subpopulation and the
      periodontal health status of the subject from whom the isolates originated,
      suggesting that the role of A. actinomycetemcomitans in periodontitis is largely
      opportunistic in the population examined. Southern blot analyses of genomic DNA
      digested with each of the restriction endonucleases MspI, RsaI, and TaqI revealed
      extremely limited genetic polymorphism of the structural leukotoxin gene, ltxA,
      and its associated promoter. All isolates hybridized to a 530-bp DNA fragment
      derived from the promoter region of the leukotoxin gene operon of a minimally
      leukotoxic A. actinomycetemcomitans strain. Deletion of the 530-bp sequence has
      been associated with significantly increased toxin production detected among
      isolates from patients with juvenile periodontitis in North America but was
      detected neither among the 88 isolates in the present collection analyzed nor
      among more than 60 strains in another population of northern European A.
      actinomycetemcomitans isolates analyzed previously.

PMID- 7714201
TI  - Evaluation of enzyme immunoassay for hepatitis B virus DNA based on anti-double
      stranded DNA.
AB  - We have evaluated a new enzyme immunoassay technology to detect the products of
      PCR-based amplification that may be applicable to routine testing of hepatitis B
      virus (HBV) DNA. Two hundred eight serum samples were studied: 73 were basal
      samples and 135 were sequential serum samples from patients with chronic
      hepatitis, some of whom were being treated with alpha interferon. We compared the
      new detection method (PCR-DNA enzyme immunoassay [DEIA]) with dot blot
      hybridization performed without prior PCR amplification and with two other
      methods for detection of PCR products: agarose gel electrophoresis with ethidium
      bromide staining (PCR-EB) and dot blot (PCR-dot blot). For hepatitis B-antigen
      positive basal samples, HBV DNA was detected in 70.4% by dot blot, 74.1% by PCR
      EB, and 100% by PCR-DEIA and PCR-dot blot; for anti-hepatitis B e-antigen basal
      samples, HBV DNA was found in 10.5% by dot blot and PCR-EB and in 42.1% by PCR
      DEIA and PCR-dot blot. Chi-square tests showed a strong association between dot
      blot and PCR-EB and between PCR-DEIA and PCR dot blot. Using PCR-dot blot as the
      reference, dot blot shows a 56.9% sensitivity and a 100% specificity, PCR-EB
      shows a 55.0% sensitivity and a 100% specificity, and PCR-DEIA shows a 95.4%
      sensitivity and a 97% specificity. We conclude that the technical advantages of
      the DEIA method and its high sensitivity and specificity may facilitate the use
      of PCR in routine testing for HBV DNA in clinical microbiology laboratories.

PMID- 7714202
TI  - Immunoblot interpretation criteria for serodiagnosis of early Lyme disease.
AB  - We monitored the antibody responses of 55 treated patients with early Lyme
      disease and physician-documented erythema migrans. Six sequential serum samples
      were obtained from patients before, during, and until one year after antibiotic
      therapy and analyzed by in-house enzyme-linked immunosorbent (ELISA) and
      immunoblot assays. An immunoblot procedure utilizing a gradient gel and an image
      analysis system was developed. A relational database management system was used
      to analyze the results and provide criteria for early disease immunoblot
      interpretation. Recommended criteria for the immunoglobulin M (IgM) immunoblot
      are the recognition of two of three proteins (24, 39, and 41 kDa). The
      recommended criteria for a positive IgG immunoblot are the recognition of two of
      five proteins (20, 24 [> 19 intensity units], 35, 39, and 88 kDa). Alternatively,
      if band intensity cannot be measured, the 22-kDa protein can be substituted for
      the 24-kDa protein with only a small decrease in sensitivity. Monoclonal
      antibodies were used to identify all these proteins except the 35-kDa protein.
      With the proposed immunoblot interpretations, the sequential serum samples were
      examined. At visit 1, the day of diagnosis and initiation of treatment, 54.5% of
      the serum samples were either IgM or IgG positive. The peak antibody response,
      with 80% of the serum samples positive, occurred at visit 2, 8 to 12 days into
      treatment. The sensitivities of the IgM and IgG immunoblot for detecting patients
      that were seropositive into the study period were 58.5 and 54.6%, respectively,
      at visit 1 and 100% at visit 2. Twenty percent of the patients remained
      seronegative throughout the study. The specificities of the IgM and IgG
      immunoblots were 92 to 94% and 93 to 96%, respectively. The IgM immunoblot and
      ELISA were similar in sensitivities, whereas the IgG immunoblot had greater
      sensitivity than the IgG ELISA (P = 0.006).

PMID- 7714203
TI  - Isolation of Coxiella burnetii from heart valves of patients treated for Q fever
      endocarditis.
AB  - Coxiella burnetii was isolated from the valve material of two patients who
      underwent valvectomy because of progressive congestive heart failure due to
      endocarditis. In each case antibiotic therapy was administered for several months
      prior to valvectomy. Classical histopathological examination of the valves did
      not reveal an etiology. However, coxiella-like organisms were demonstrated in
      valvular material with Koster, Stamp, and Giemsa stains, and the organisms were
      grown in cell culture. Antibody titers were consistent with the diagnosis of
      chronic C. burnetii infection. This report illustrates the advantage of simple
      and fast staining techniques and cell culture for the demonstration and isolation
      of C. burnetii in the heart valve tissue of patients with Q fever endocarditis.

PMID- 7714205
TI  - Rapid detection and characterization of foot-and-mouth disease virus by
      restriction enzyme and nucleotide sequence analysis of PCR products.
AB  - Reverse transcription coupled with PCR was used for the detection of foot-and
      mouth disease virus serotypes A, C, and O in organ extracts from experimentally
      infected cattle. Primers were selected from conserved sequences flanking the
      genome region coding for the major antigenic site of the capsid located in the C
      terminal part of viral protein 1 (VP1). Because this region of the capsid is
      highly variable its coding sequence is considered to be the most appropriate for
      the characterization of virus isolates and, therefore, for the determination of
      the epidemiological relationships between viruses of the same serotype. For
      differentiation between serotypes and for detailed characterization of individual
      virus isolates restriction enzyme cleavage and nucleotide sequence analysis of
      the respective PCR products were carried out. In order to minimize the time
      required for sample preparation from clinical material, viral RNA was released
      from particles by heating the sample for 5 min at 90 degrees C. Finally, an air
      thermocycler was used, which allows performance of a PCR of 30 cycles in
      approximately 20 min. The results show that reverse transcription PCR followed by
      restriction enzyme analysis and/or nucleotide sequence analysis of the PCR
      products is useful for the rapid detection and differentiation of foot-and-mouth
      disease virus.

PMID- 7714204
TI  - Reduced inhibition of Candida albicans adhesion by saliva from patients receiving
      oral cancer therapy.
AB  - The effect of saliva on the adhesion of Candida albicans to epithelial cells was
      examined in vitro by using saliva from healthy controls and patients with oral
      squamous cell carcinoma. The adhesion of C. albicans to established epithelial
      tumor cells was reduced by 40% by salivary treatment of the C. albicans or
      epithelial cells. The inhibitory activity of saliva was almost completely
      abolished by anti-secretory immunoglobulin A antibody, concanavalin A, and
      mannose. Compared with saliva from healthy individuals, that from patients who
      had received chemoradiotherapy for oral carcinoma showed reduced suppression of
      C. albicans adhesion, which accompanied decreased salivary secretory
      immunoglobulin A and lactoferrin concentrations. A greater number of C. albicans
      cells adhered to buccal cells obtained from patients who had received
      chemoradiotherapy than to those from healthy individuals. Treatment of either
      epithelial cells or C. albicans with anticancer drugs induced an increase in
      adherence of epithelial cells and yeast cells. In contrast, concanavalin A- and
      mannose-pretreated C. albicans exhibited reduced adhesion to epithelial cells. No
      further decrease of C. albicans adhesion was observed when both epithelial cells
      and yeast phase C. albicans were treated with mannose. In conclusion, the
      inhibition of C. albicans adhesion by saliva depends largely on mannose residues
      on salivary glycoproteins and mannose is one of the binding ligands on both C.
      albicans and epithelial cells. In addition, anticancer therapy may induce oral C.
      albicans overgrowth by decreasing salivation and the concentrations of
      glycoproteins in saliva inhibiting C. albicans adhesion and by increasing the
      adhesive properties of both C. albicans and oral epithelial cells.

PMID- 7714206
TI  - Evaluation of ligase chain reaction for use with urine for identification of
      Neisseria gonorrhoeae in females attending a sexually transmitted disease clinic.
AB  - The high sensitivity of nucleic acid amplification tests such as ligase chain
      reaction (LCR) has the potential to simplify specimen collection for the
      microbiologic diagnosis of gonorrhea. We screened first-void urine specimens from
      283 women attending a Birmingham, Ala., sexually transmitted disease (STD) clinic
      by using LCR and compared the results to those of cervical and urethral cultures
      for gonorrhea diagnosis. Fifty-three (18.7%) women had positive cervical cultures
      for gonorrhea, and 41 of the 53 (77%) also had positive urethral cultures. One
      additional patient had only a positive urethral culture (the cervical gonorrhea
      culture was negative). LCR testing of urine specimens for gonorrhea yielded
      positive results for 51 of 54 (94.4%) women with positive cervical or urethral
      cultures. Of 229 women with both urethral and cervical cultures negative for
      gonorrhea, 2 (0.8%) had positive urine LCR results as well. To resolve the
      discrepancies between urine LCR and culture results, LCR tests of simultaneously
      collected urethral and cervical swab specimens and LCR tests of the same urine
      specimens using different nucleotide primers were conducted. After evaluation of
      five discrepant results, the sensitivity, specificity, positive predictive value,
      and negative predictive value of LCR for the detection of gonorrhea in urine
      specimens were 94.6%, 100%, 100%, and 98.7%, respectively. We conclude that urine
      LCR testing for Neisseria gonorrhoeae is a practical alternative to culture for
      the detection of gonorrhea in women. Urine testing for STD diagnosis has the
      potential to simplify and expand the opportunities for STD screening and
      surveillance of women.

PMID- 7714207
TI  - Typing Neisseria meningitidis by analysis of restriction fragment length
      polymorphisms in the gene encoding the class 1 outer membrane protein:
      application to assessment of epidemics throughout the last 4 decades in China.
AB  - A typing method was developed for Neisseria meningitidis serogroup A by analysis
      of restriction fragment length polymorphisms (RFLP) of the class 1 outer membrane
      protein gene (porA). By using appropriate primers, an approximately 1,116-bp
      fragment of the porA gene was amplified by PCR and then was digested with the
      restriction endonuclease MspI. The digestion products were separated on 10%
      polyacrylamide gels and were stained with silver. One hundred three clinical
      isolates of group A N. meningitidis from 17 provinces of China collected over a
      26-year period were analyzed. Results of MspI-generated RFLP profiles of PCR
      amplified porA genes were compared with those obtained by conventional
      serosubtyping. There was a band of about 400 bp common to all strains examined,
      and the 103 strains of serogroup A resulted in 22 unique RFLP patterns. The
      differences in bands could be observed mainly in the range of 120 to 280 bp. The
      smaller fragments were useful in distinguishing meningococci with the same
      serosubtype. Three epidemic periods were characterized by the presence of three
      distinct genotypes (a1, a2, and a3), accounting for 74.5% of the strains examined
      (3.88, 26.21, and 44.66%, respectively). Three predominant RFLP patterns were
      correlated epidemiologically with cycles of epidemic meningococcal meningitis and
      were well-matched to the predominant serosubtypes (P1.9, P1.7, 10, and P1.9) that
      presented at the same prevalence cycles. The genotyping yielded information that
      allowed strains from one epidemic to be distinguished from those from another
      that would have been indistinguishable if only serotyping and serosubtyping were
      available. Therefore, the PCR-RFLP typing method was very useful in the
      epidemiologic investigation of group A meningococcal meningitis.

PMID- 7714208
TI  - In vitro growth of the microsporidian Septata intestinalis from an AIDS patient
      with disseminated illness.
AB  - A new species of microsporidian, Septata intestinalis, was recently recognized as
      an opportunistic pathogen of AIDS patients. In this study, it was cultured from
      the nasopharyngeal aspirate of a human immunodeficiency virus type 1-infected
      patient with disseminated microsporidiosis. In human embryonic lung cells exposed
      to S. intestinalis, a cytopathic effect appeared within 28 days as foci of
      rounded up cells. Thin-section electron microscopy showed a variety of
      developmental stages of the microsporidium within parasitophorous vacuoles. In
      monocyte-derived macrophages, evidence of infection and development of the
      parasite was demonstrated by light and electron microscopy. In both infected
      human embryonic lung cells and monocyte-derived macrophages, a network of septa
      separated individual spores. Partial sequencing of the RNA small-subunit gene
      (16S rDNA gene) confirmed the identity of this parasite as S. intestinalis. This
      is the first report of the isolation of S. intestinalis in vitro and provides
      evidence that the parasite can be disseminated by macrophages.

PMID- 7714209
TI  - First reported case of Aspergillus granulosus infection in a cardiac transplant
      patient.
AB  - We report a case of disseminated infection with Aspergillus granulosus in a
      cardiac transplant recipient on immunosuppressive therapy. This is the first
      reported case in which this organism has been described as a pathogen. This
      organism bears morphological features different from those of more common
      Aspergillus species and should be considered a potential pathogen in
      immunocompromised patients.

PMID- 7714211
TI  - Evaluation of SHARP signal system for enzymatic detection of amplified hepatitis
      B virus DNA.
AB  - The sensitivity, specificity, reproducibility, detection level, and
      quantification potential of the SHARP Signal System for enzymatic detection of
      amplified hepatitis B virus (HBV) DNA in clinical samples were evaluated by
      testing 104 samples in parallel in a SHARP PCR, an in-house HBV PCR, and a dot
      blot hybridization assay for semiquantification. SHARP PCR showed a sensitivity
      of 100%, a specificity of 92.3% (resolved, 100%), a reproducibility of 92.3% (all
      discrepant serum samples involved very low levels of HBV DNA), and a detection
      level of at least 3.5 pg/ml. Clinically relevant quantification of the amplified
      products was not feasible.

PMID- 7714210
TI  - Comparison of GonoGen, GonoGen II, and MicroTrak direct fluorescent-antibody test
      with carbohydrate fermentation for confirmation of culture isolates of Neisseria
      gonorrhoeae.
AB  - When testing 248 clinical isolates of Neisseria gonorrhoeae, the sensitivity was
      100% with GonoGen (Becton Dickinson Microbiology Systems), 99.6% (247 of 248)
      with GonoGen II (Becton Dickinson), 97.2% (241 of 248) with the MicroTrak direct
      fluorescent-antibody test (Syva), and 97.6% (242 of 248) with Rapid Fermentation
      Agar carbohydrates (Remel). Of 62 isolates of other Neisseria species, none was
      misidentified as N. gonorrhoeae by GonoGen, MicroTrak, or Rapid Fermentation Agar
      carbohydrates but 7 (31.8%) of 22 isolates of N. meningitidis gave strong,
      repeatedly false-positive results with GonoGen II. The sensitivity of all four
      assays was good to excellent, but all positive GonoGen II results should be
      confirmed with an independent assay, especially when isolates are recovered from
      sites where N. meningitidis is likely. Positive results from any of the assays
      should be routinely confirmed when dictated by specific clinical, legal, or
      microbiological circumstances.

PMID- 7714212
TI  - Serologic evaluation of human immunodeficiency virus type 1-infected individuals
      from Argentina and the United States indicates a similar distribution of subgroup
      B isolates.
AB  - Utilizing peptides based on the V3 region of gp120, we undertook a serologic
      examination of human immunodeficiency virus type 1 (HIV-1)-infected individuals
      from Argentina to determine if prevalent HIV-1 isolates could be identified in
      this population. Our findings suggest that a similar pool of HIV-1 subgroup B
      isolates exists in both Argentina and the United States.

PMID- 7714213
TI  - Diagnostic value of detecting JC virus DNA in cerebrospinal fluid of patients
      with progressive multifocal leukoencephalopathy.
AB  - JC virus DNA was detected by PCR in the cerebrospinal fluid of 17 of 23 (73.9%)
      patients with confirmed cases of progressive multifocal leukoencephalopathy and 2
      of 48 (4.2%) controls without progressive multifocal leukoencephalopathy. The
      sensitivity and specificity of this PCR were 74 and 95.8%, respectively, while
      the positive and negative predictive values were 89.5 and 88.5%, respectively.

PMID- 7714215
TI  - Oligotrophic bacteria isolated from clinical materials.
AB  - Oligotrophic bacteria (oligotrophs) are microorganisms that grow in extremely
      nutritionally deficient conditions in which the concentrations of organic
      substances are low. Many oligotrophic bacteria were isolated from clinical
      materials including urine, sputum, swabbings of the throat, vaginal discharges,
      and others. Seventy-seven strains of oligotrophic bacteria from 871 samples of
      clinical material were isolated. A relatively higher frequency of isolation of
      oligotrophic bacteria was shown in drainage, sputum, and throat specimens. Eleven
      strains of the obligate oligotrophic bacteria recovered showed scant growth on
      enriched medium, blood agar, and nutrient agar. Oligotrophic bacteria were
      isolated from a variety of materials but were not found in routine bacteriologic
      examinations in the hospital laboratory. The clinical significance of such
      oligotrophic bacteria is uncertain.

PMID- 7714214
TI  - Specific amplification of Rickettsia japonica DNA from clinical specimens by PCR.
AB  - The gene encoding the 17,000-molecular-weight genus-common antigen (17K genus
      common antigen) has been cloned and sequenced from Rickettsia japonica. The
      primer pair used for PCR was designed from this sequence. A 357-bp fragment was
      observed by amplifying the genomic DNA from R. japonica and also the DNA from
      blood clots of patients with spotted fever group rickettsiosis. The results
      indicated that this method is suitable for the diagnosis of spotted fever group
      rickettsiosis in Japan.

PMID- 7714216
TI  - Specific recognition of purified Cu,Zn superoxide dismutase from Aspergillus
      fumigatus by immune human sera.
AB  - Sera from 22 (84.6%) of 26 patients with confirmed Aspergillus infections
      recognized a purified Cu,Zn superoxide dismutase from A. fumigatus on Western
      blots (immunoblots). Sera from 32 (71%) of 45 patients with suspected Aspergillus
      infections were reactive to the superoxide dismutase. Normal human sera and sera
      from patients with other infections were unreactive.

PMID- 7714217
TI  - A new sensitive sandwich enzyme-linked immunosorbent assay to detect galactofuran
      in patients with invasive aspergillosis.
AB  - A double-direct sandwich enzyme-linked immunosorbent assay that uses a rat anti
      galactomannan monoclonal antibody as the acceptor and detector antibody was
      designed. This immunoassay, which detects less than 1 ng of galactomannan per ml,
      was assessed in a retrospective study with samples from patients with invasive
      aspergillosis. Serum is more appropriate than urine for use in the search for
      circulating galactomannan. Antigenemia does not have a transient character.
      Galactomannan can be detected at least 39 days before the death of the patients.

PMID- 7714218
TI  - Use of solid-phase immune electron microscopy for classification of Norwalk-like
      viruses into six antigenic groups from 10 outbreaks of gastroenteritis in the
      United States.
AB  - Norwalk-like viruses observed in fecal specimens from 10 outbreaks of
      gastroenteritis investigated in the United States between 1987 and 1992 were
      analyzed by solid-phase immune electron microscopy. Outbreak virus strains were
      classified into six antigenic groups: the four types (UK1 to UK4) previously
      defined in the United Kingdom, Norwalk virus, and the Oklahoma agent that was
      newly defined in this study. The diversity of antigenic types demonstrated in
      these outbreaks was greater than previously recognized and will serve as a basis
      for characterization of these strains at the molecular level.

PMID- 7714220
TI  - Clinical impact of rapid in vitro susceptibility testing and bacterial
      identification.

PMID- 7714219
TI  - Characterization of Paracoccidioides brasiliensis isolates by random amplified
      polymorphic DNA analysis.
AB  - We initially used 25 different random primers in order to test their ability to
      generate random amplified polymorphic DNA fragments from the dimorphic human
      pathogenic fungus Paracoccidioides brasiliensis. From the tested primers we chose
      five to distinguish between seven isolates of this microorganism. The DNA
      amplification patterns allowed clear differentiation of the seven isolates into
      two distinct groups with only 35% genomic identity. One of these groups contained
      two subgroups with 81% genetic similarity. The random amplified polymorphic DNA
      analysis method proved to be a good tool for analyzing and comparing different
      genomes of P. brasiliensis isolates.

PMID- 7714221
TI  - More on drugs and pregnancy.

PMID- 7714222
TI  - Assessment of the efficacy of buspirone in patients affected by generalized
      anxiety disorder, shifting to buspirone from prior treatment with lorazepam: a
      placebo-controlled, double-blind study.
AB  - Forty-four patients with DSM-III-R generalized anxiety disorder participated in
      this double-blind, randomized study. Patients were on a benzodiazepine before the
      study and were stabilized on 3 to 5 mg/day lorazepam for 5 weeks (weeks 0 to 5).
      Thereafter, they were randomized to 15 mg/day buspirone or placebo for the
      following 6 weeks (weeks 6 to 11). During the first 2 weeks of double-blind,
      randomized treatment (weeks 6 to 7), lorazepam was tapered off. During weeks 12
      to 13, patients received single-blind placebo. Assessment included the Hamilton
      Rating Scale for Anxiety, the State-Trait Anxiety Inventory, the Zung and Eddy
      Self-Rating Scale of Anxiety Symptoms, the Hamilton Rating Scale for Depression,
      and the Rome Depression Inventory, completed at weeks 0, 5, 6, 7, 8, 9, 11, and
      13. Side effects were assessed through the Dosage Treatment Emergent Symptoms at
      the same times. The benzodiazepine-withdrawal syndrome was evaluated through a 27
      symptom checklist (Clinical-Rated Benzodiazepine Withdrawal Symptom Schedule) at
      weeks 0, 5, 6, 7, 11, and 13. The results showed that buspirone was more
      effective than placebo and comparable to lorazepam. Buspirone-treated patients
      showed no rebound anxiety or benzodiazepine-withdrawal syndrome compared with
      placebo. Buspirone caused fewer side effects than lorazepam and was not different
      from placebo in this respect. Finally, buspirone maintained its anxiolytic effect
      for at least 2 weeks after the discontinuation of treatment.

PMID- 7714223
TI  - Efficacy trial of the 5-HT2 antagonist MDL 11,939 in patients with generalized
      anxiety disorder.
AB  - The purpose of this study was to assess the anxiolytic effect of MDL 11,939, a
      selective 5-HT2 receptor antagonist, in patients with generalized anxiety
      disorder. After a 1-week placebo lead-in period, 72 healthy male outpatients
      meeting DSM-III-R criteria for generalized anxiety disorder were randomized to
      MDL 11,939, 32 mg thrice daily (N = 37), or placebo (N = 35) for 6 weeks. At the
      end of treatment, MDL 11,939 showed a 7.2-point (30%) decrease in Hamilton Rating
      Scale for Anxiety scores compared with a 5.7-point (23%) decrease with placebo,
      but the difference was not significant (p > 0.05). The incidence of adverse
      events between treatments was similar. MDL 11,939 was well tolerated but did not
      demonstrate significant anxiolytic effects in this pilot study.

PMID- 7714224
TI  - Effect of fluoxetine on anger in symptomatic volunteers with borderline
      personality disorder.
AB  - Clinical data and uncontrolled observations have suggested that fluoxetine is
      helpful in some patients with borderline personality disorder. This article
      describes the results of a 13-week double-blind study of volunteer subjects with
      mild to moderately severe borderline personality disorder. Thirteen fluoxetine
      recipients and nine placebo recipients received treatment. Pretreatment and
      posttreatment measures were obtained for global mood and functioning, anger, and
      depression. The most striking finding from this study was a clinically and
      statistically significant decrease in anger among the fluoxetine recipients. This
      decrease was independent of changes in depression. These data support previous
      observations that fluoxetine may reduce anger in patients with borderline
      personality disorder. The number of subjects in this study was small, the placebo
      responsiveness was high, and the clinical characteristics of the patients were in
      the mild to moderate range of severity. The data cannot be extrapolated to more
      severely ill borderline patients, but further study of fluoxetine and other
      selective serotonin reuptake inhibitors is indicated in this population.

PMID- 7714226
TI  - Acute and subchronic effects of nefazodone and imipramine on highway driving,
      cognitive functions, and daytime sleepiness in healthy adult and elderly
      subjects.
AB  - The acute and subchronic effects of two dosages of a new serotonergic
      antidepressant, nefazodone, and those of the tricyclic imipramine were examined
      in a double-blind, crossover, placebo-controlled study. Twenty-four healthy
      subjects from two age groups (12 adults and 12 elderly from both sexes) received
      the four treatments (nefazodone, 100 and 200 mg twice daily; imipramine, 50 mg
      twice daily; and placebo) for 7 days with a 7-day washout period. Measurements
      were performed after the morning doses on day 1 and day 7. These included a
      standard over-the-road highway driving test, a psychomotor test battery, and
      sleep latency tests. Blood samples were taken on both days and analyzed to
      determine concentrations of parent drugs and their major metabolites. The main
      results showed that the reference drug, imipramine, had a detrimental effect
      after a single dose on lateral position control in the driving test, primarily in
      the adult group, that diminished after repeated dosing. Minor impairment on
      psychomotor test performance was found with both days. On the other hand, a
      single administration of both doses of nefazodone did not impair highway driving
      performance (even showed some improvement) and had no or only minor effects on
      psychomotor performance. After repeated dosing, nefazodone 200 mg twice daily
      (but not the 100-mg dose) produced slight impairment of lateral position control;
      dose-related impairment of cognitive and memory functions was found. The effects
      of nefazodone were generally in the same direction in both age groups.
      Significant correlations were found between steady-state concentrations of
      nefazodone in plasma (200-mg, twice-daily condition) as well as imipramine, and
      reaction time changes in a memory scanning task. Neither drug appeared to induce
      daytime sleepiness as measured by the sleep latency tests.

PMID- 7714225
TI  - Orally administered progesterone enhances sensitivity to triazolam in
      postmenopausal women.
AB  - An endogenously formed metabolite of progesterone, 3 alpha-hydroxy-5 alpha
      dihydroprogesterone (3 alpha-OH-5 alpha-DHP) modulates the gamma-aminobutyric
      acid receptor complex and plays a physiologic role in brain excitability
      regulation. On the basis of in vitro observations of 3 alpha-OH-5 alpha-DHP
      enhanced [3H]flunitrazepam binding, we investigated the potential clinical effect
      of coadministering oral progesterone and triazolam. Sixteen postmenopausal women
      were randomly assigned to receive either intravenous triazolam plus oral
      progesterone 300 mg (TRZPROG) or intravenous triazolam plus oral placebo (TRZ).
      Triazolam was infused until 0.5 mg was given or until a predetermined maximal
      response was attained. Pharmacodynamic evaluation included DSST, continuous
      performance test, hand-eye coordination, short-term memory, and sedation. Effect
      ratios were calculated as the ratio of area under the effect-time curve to area
      under the curve (AUC). Variants of the sigmoid Emax model were fit to the data
      from the three psychomotor performance tests. A triazolam dose of less than 0.5
      mg was administered to seven of eight subjects in the TRZPROG and five of eight
      subjects in the TRZ group, resulting in lower triazolam AUC values for the
      TRZPROG than for the TRZ group (p = 0.0275). There was clear evidence for a
      pharmacodynamic interaction. Mean effect ratios for all tests were greater in the
      TRZPROG group than in the TRZ group (DSST, p = 0.0097; continuous performance
      test, p = 0.0338; hand-eye coordination, p = 0.0041). The TRZPROG group had lower
      EC50 values than the TRZ group (DSST, p = 0.0435; continuous performance test, p
      = 0.0381; hand-eye coordination, p = 0.0154).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714227
TI  - Switch in treatment from tricyclic antidepressants to moclobemide: a new
      generation monoamine oxidase inhibitor.
AB  - The combination of classic monoamine oxidase inhibitors (MAOIs) and tricyclic
      antidepressant drugs (TCAs) has been associated with a variety of adverse events.
      A switch in treatment from TCAs to moclobemide, a reversible and selective
      inhibitor of MAO-A, was investigated in a double-blind, placebo-controlled study
      in healthy volunteers. Two groups of 12 subjects were treated with either
      amitriptyline (75 mg/day) or clomipramine (100 mg/day) until steady-state
      conditions had been attained (14 days). Treatment with the TCAs was discontinued
      abruptly and switched to either a therapeutic dose regimen of moclobemide (300
      mg/day) or placebo. The tolerability and safety pattern did not reveal any
      clinically relevant differences between moclobemide and placebo recipients, nor
      was there any sign of a pharmacokinetic interaction between the TCAs and
      moclobemide. In conclusion, the findings of this study suggest that therapeutic
      doses of moclobemide up to 300 mg daily can be given 24 hours after the last dose
      of treatment with either amitriptyline or clomipramine without major risks.

PMID- 7714228
TI  - Buprenorphine treatment of refractory depression.
AB  - Opiates were used to treat major depression until the mid-1950s. The advent of
      opioids with mixed agonist-antagonist or partial agonist activity, with reduced
      dependence and abuse liabilities, has made possible the reevaluation of opioids
      for this indication. This is of potential importance for the population of
      depressed patients who are unresponsive to or intolerant of conventional
      antidepressant agents. Ten subjects with treatment-refractory, unipolar,
      nonpsychotic, major depression were treated with the opioid partial agonist
      buprenorphine in an open-label study. Three subjects were unable to tolerate more
      than two doses because of side effects including malaise, nausea, and dysphoria.
      The remaining seven completed 4 to 6 weeks of treatment and as a group showed
      clinically striking improvement in both subjective and objective measures of
      depression. Much of this improvement was observed by the end of 1 week of
      treatment and persisted throughout the trial. Four subjects achieved complete
      remission of symptoms by the end of the trial (Hamilton Rating Scale for
      Depression scores < or = 6), two were moderately improved, and one deteriorated.
      These findings suggest a possible role for buprenorphine in treating refractory
      depression.

PMID- 7714229
TI  - Effects of the cholinomimetic SDZ ENS-163 on scopolamine-induced cognitive
      impairment in humans.
AB  - Scopolamine-induced cognitive impairment was used in healthy men to evaluate the
      central nervous system activity of the new cholinomimetic SDZ ENS-163. Eighteen
      subjects were treated in a crossover design with oral placebo/intravenous saline,
      50 mg of oral SDZ ENS-163/intravenous saline, oral placebo/0.4 mg of intravenous
      scopolamine, and 50 mg of oral SDZ ENS-163/0.4 mg of intravenous scopolamine. The
      administration of placebo with scopolamine caused significant cognitive
      impairment, as assessed by the Computerized Neuropsychological Test Battery
      (CNTB), and also decreased salivation and heart rate. In contrast, SDZ ENS-163
      with saline had no effect on CNTB scores, increased salivation, and increased
      heart rate. Despite the observed cholinomimetic effects of SDZ ENS-163 when
      administered with saline, the changes in CNTB scores, heart rate, and salivation
      were indistinguishable between placebo/scopolamine and SDZ ENS-163/scopolamine.
      Thus, 50 mg of oral SDZ ENS-163 has cholinomimetic activity in normal men, but
      this dose is insufficient to reverse the muscarinic effects of 0.4 mg of
      intravenous scopolamine.

PMID- 7714230
TI  - Cocaine abuse and dependence.
AB  - Western countries experienced a widespread cocaine epidemic during the 1980s, and
      the number of frequent users has not declined in this decade. A key factor in the
      development of this epidemic has been the introduction of "crack," an affordable
      form of cocaine that appears to be more addicting than the powder. Epidemiologic
      studies indicate a high incidence of polysubstance abuse among cocaine abusers
      and probable gender differences in patterns of abuse and response to treatment.
      An abstinence syndrome has been documented in outpatients after the acute
      cessation of cocaine; the symptoms perhaps depend on the presence of cues to
      evoke craving of cocaine and thus are not detected in inpatient settings. Cocaine
      is a psychostimulant drug that possesses euphorigenic and reinforcing properties.
      The fact that various animal species self-administer cocaine through the
      intravenous route provides a reliable animal model for the study of the molecular
      mechanism of cocaine action and for the characterization of the anatomical
      substrates responsible for the rewarding properties of the drug. A multisynaptic,
      allocorticolimbic-accumbens-pallidal circuitry has been identified that seems to
      play an important role. This pathway may also be part of the neuronal substrates
      that mediate the reinforcing properties of other classes of abused drugs and,
      perhaps, motivated behavior in general. Because of this potent reinforcing nature
      of cocaine in humans, the problem of designing effective therapy for its
      addiction has not been simply solved. Clinical treatments, guided by animal
      studies and designed for specific attack of symptoms of the abstinence syndrome,
      craving and anhedonia, have been tested. To date, only a few agents have proved
      effective in controlled trials (amantadine, bromocriptine, carbamazepine, and
      desipramine) and these have limitations of side effects or delayed onset of
      action. Agents that interact with specific subcomponents of the dopamine system
      or its connections offer promise for the development of successful agents to
      treat cocaine abuse and craving in humans.

PMID- 7714231
TI  - Neuroleptic malignant-like syndrome due to cyclobenzaprine?

PMID- 7714232
TI  - Recurrent depression after sumatriptan administration for treatment of migraine.

PMID- 7714233
TI  - Digoxin encephalopathy presenting as mood disturbance.

PMID- 7714234
TI  - Amantadine in the treatment of sexual dysfunction associated with selective
      serotonin reuptake inhibitors.

PMID- 7714235
TI  - Letter regarding "Response to antidepressants and cancer: cause for concern?".

PMID- 7714236
TI  - Distribution and development of beta-adrenergic receptors in the rat olfactory
      bulb.
AB  - Beta-adrenergic stimulation appears to be involved in the establishment of both
      learned olfactory preferences and functional changes in the olfactory bulb of
      young rats. We examined the postnatal development of beta-adrenergic receptors
      within the main olfactory bulb to determine the density and distribution of these
      receptors. To quantify beta-adrenergic receptor density, olfactory bulb
      homogenates from postnatal day (PND) 1, 6, 12, and 19 rats were assessed for
      receptor binding with 125I-iodopindolol. In addition, receptor autoradiography
      was performed with the selective beta 1 antagonist ICI 89,406 and selective beta
      2 antagonist ICI 118,551 on tissue sections from PND 1-30 rats to examine the
      distribution of the beta-adrenergic receptor subtypes. We observed both an
      increase in receptor density with increasing age and the formation of distinct
      spatial distributions of the two beta receptor subtypes within the bulbar lamina.
      Beta-adrenergic receptors were located in both deep and superficial layers of the
      bulb. Specifically, beta 1 receptors were present in the granule cell, internal
      plexiform and glomerular layers. beta 2 receptors were present in the granule
      cell, internal plexiform, external plexiform, and glomerular layers. High levels
      of beta 2 receptors also were visible in the meningeal layers between the two
      bulbs. High densities of beta 1 and beta 2 adrenergic receptors were present
      within different sets of individual glomeruli by PND 12-19, and the number of
      these foci increased with age. The knowledge of beta-noradrenergic receptor
      localization in the bulb may provide the basis for understanding the action of
      norepinephrine on neural processes in the developing olfactory bulb.

PMID- 7714237
TI  - Structure and innervation of longitudinal and transverse abdominal muscles of the
      cricket, Gryllus bimaculatus.
AB  - Detailed morphological and physiological studies on the insect abdominal muscles,
      including their innervation and neuromuscular transmission, are essential for
      understanding their important role in respiratory movements. There are both
      longitudinal and transverse muscles in the ventral abdominal segments of the
      cricket, Gryllus bimaculatus. Muscle 202 was selected as an example of a
      longitudinal muscle. This muscle is, on average, 1.4 mm long, paired on both
      sides of the abdomen, and consists of 127 fibers whose mean maximum diameter is
      32 microns; the average sarcomere length is 8.1 microns. It is innervated by two
      ipsilateral motoneurons in the second abdominal ganglion, the axons of which run
      in the ipsilateral first nerve root of the third abdominal ganglion. Two motor
      axons run in parallel from the two cell bodies and innervate in close proximity.
      Accordingly, large and small excitatory junctional potentials (EJPs) are recorded
      from the same fiber with slightly different thresholds when the first nerve root
      of the third abdominal ganglion is stimulated. Muscle 203, which is a transverse
      muscle that extends across the fifth abdominal sternum and is located over the
      fourth abdominal ganglion and muscle 202 on both sides, is, on average, 2.9 mm
      long and consists of 86 fibers with a maximum diameter of 33 microns. The average
      sarcomere length is 7.9 microns. The right or left half of the muscle is
      innervated mainly by a contralateral motoneuron in the third abdominal ganglion
      through the ipsilateral first nerve root of the third abdominal ganglion. Nerve
      branches of the first nerve root also reach muscles 188 and 218. Muscle 203 is
      additionally innervated by the first nerve roots of abdominal ganglia 1, 2, and
      4. These innervations were ascertained both electrophysiologically and
      histologically. Individual muscle fibers of muscle 203 produced small EJPs in
      response to stimulation of the first nerve roots of abdominal ganglia 2, 3, and 4
      and large EJPs in response to stimulation of the root from the first abdominal
      ganglion. The large and small EJPs in muscle 203 have properties similar to those
      in muscle 202.

PMID- 7714238
TI  - Insulin-like growth factor-1 mRNA is increased in deafferented hippocampus:
      spatiotemporal correspondence of a trophic event with axon sprouting.
AB  - Deafferentation is known to induce axonal sprouting in adult brain, but the
      signals that direct this response are not understood. To evaluate the possible
      roles of insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor
      (bFGF) in central axonal sprouting, the present study used in situ hybridization
      to evaluate IGF-1 and bFGF mRNA expression in entorhinal deafferented rat
      hippocampus. Alternate tissue sections were processed for Fink-Heimer
      impregnation of axonal degeneration, Bandeiraea simplicifolia (BS-1) labeling of
      microglia, and glial fibrillary acidic protein immunocytochemistry. In control
      hippocampus, IGF-1 mRNA was localized to a few neurons, with no labeled cells in
      the dentate gyrus molecular layer; bFGF cRNA hybridization was diffuse in
      dendritic fields but was dense in CA2 stratum pyramidale. Both mRNA species were
      increased by deafferentation. The distribution of elevated IGF-1 mRNA
      corresponded precisely to fields of axonal degeneration and was greatest in the
      dentate gyrus outer molecular layer and stratum lacunosum moleculare. In these
      fields, IGF-1 mRNA was elevated by 2 days, reached maximal levels at 4 days, and
      declined by 10 days postlesion. Double labeling revealed that the majority of IGF
      1 cRNA-labeled cells were microglia. In deafferented hippocampus, bFGF mRNA was
      broadly increased across fields both containing and lacking axonal degeneration.
      In the dentate, bFGF mRNA levels peaked at 5 days postlesion and remained
      elevated through 14 days. These results demonstrate that reactive microglia
      within deafferented hippocampal laminae express IGF-1 mRNA just prior to and
      during the period of reactive axonal growth and suggest that IGF-1 plays a role
      in directing the sprouting of spared afferents into these fields.

PMID- 7714239
TI  - Phaseolus vulgaris-leucoagglutinin tracing of commissural fibers to the rat
      dentate gyrus: evidence for a previously unknown commissural projection to the
      outer molecular layer.
AB  - Numerous studies have shown a lamina-specific termination of commissural fibers
      to the dentate gyrus in the inner molecular layer. However, the exact course and
      arborization pattern of individual fibers remained unknown. In this study, the
      commissural fiber tract to the dentate gyrus of the rat has been studied using
      the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L), which labels
      individual axons and their collaterals. Following iontophoretic application of
      the tracer, anterogradely labeled fibers were followed through the posterior
      basal fornix and medial fimbria where they formed a dense fiber bundle. Labeled
      fibers then entered the dentate gyrus close to the medial blade of the granule
      cell layer where they separated and traversed the hilus. Only in those cases
      where the injection also involved CA3 pyramidal cells could axons arborizing in
      the hilus be observed. Typically, fibers that continued into the molecular layer
      did not arborize in the hilus. Upon their entrance into the molecular layer,
      these fibers changed direction, gave off several collaterals, and followed a new
      path parallel to the granule cell layer where they preferentially formed en
      passant contacts. These commissural fibers to the inner molecular layer
      terminated in a wide septotemporal (longitudinal) extension. However, a
      considerable number of fibers reached the outer molecular layer where some of
      them formed extensive arborizations. Moreover, these commissural fibers to the
      outer molecular layer appeared to be restricted to the hippocampal lamella,
      corresponding to the level of the contralateral injection site. These data
      suggest the existence of three commissural projections to the rat dentate gyrus:
      (1) commissural fibers to the hilus arising from CA3 neurons, (2) commissural
      fibers to the inner molecular layer, and, (3) commissural fibers to the outer
      molecular layer.

PMID- 7714240
TI  - Distribution of four types of synapse on physiologically identified relay neurons
      in the ventral posterior thalamic nucleus of the cat.
AB  - This study was aimed at providing quantitative data on the thalamic circuitry
      that underlies the central processing of somatosensory information. Four
      physiologically identified thalamocortical relay neurons in the ventral posterior
      lateral nucleus (VPL) of the cat thalamus were injected with horseradish
      peroxidase and subjected to quantitative electron microscopy after pre- or
      postembedding immunostaining for gamma-aminobutyric acid to reveal synaptic
      terminals of thalamic inhibitory neurons. The four cells all had rapidly adapting
      responses to light mechanical stimuli applied to their receptive fields, which
      were situated on hairy or glabrous skin or related to a joint. Their dendritic
      architecture was typical of cells previously described as type I relay cells in
      VPL, and they lacked dendritic appendages. Terminals ending in synapses on the
      injected cells were categorized as RL (ascending afferent), F (inhibitory), PSD
      (presynaptic dendrite), and RS (mainly corticothalamic) types and were quantified
      in reconstructions of serial thin sections. RL and F terminals formed the
      majority of the synapses on proximal dendrites (approximately 50% each). The
      number of synapses formed by RL terminals declined on intermediate dendrites, but
      those formed by F terminals remained relatively high, declining to moderate
      levels (20-30%) on distal dendrites. RS terminals formed moderate numbers of the
      synapses on intermediate dendrites and the majority (> 60%) of the synapses on
      distal dendrites. Synapses formed by PSDs were concentrated on intermediate
      dendrites and were few in number (approximately 6%). They formed synaptic triads
      with F terminals and rarely with RL terminals. On somata, only a few synapses
      were found, all made by F terminals. The total number of synapses per cell was
      calculated to be 5,584-8,797, with a density of 0.6-0.9 per micrometer of
      dendritic length. Of the total, RL terminals constituted approximately 15%, F
      terminals approximately 35%, PSD terminals approximately 5%, and RS terminals
      approximately 50%. These results provide the first quantitative assessment of the
      synaptic architecture of thalamic somatic sensory relay neurons and show the
      basic organizational pattern exhibited by representatives of the physiological
      type of relay neurons most commonly encountered in the VPL nucleus.

PMID- 7714241
TI  - Localization of amyloid P component in human brain: vascular staining patterns
      and association with Alzheimer's disease lesions.
AB  - Amyloid P component is a normal serum protein that is highly conserved across
      phylogeny. Although it resembles the classic acute-phase reactant C-reactive
      protein, and is considered to be a normal extracellular matrix component, its
      physiologic role in humans is unknown. Amyloid P component is also colocalized
      with accumulations of all recognized forms of amyloid. The present study uses
      light and electron microscopy to compare the cerebral localization of amyloid P
      component in cases with (n = 19) and without (n = 15) Alzheimer's disease (AD).
      In non-AD cases, amyloid P component was predominantly localized to the
      cerebrovasculature. Perivascular staining was observed in most cases, more so in
      the white than in the gray matter. In AD cases, amyloid P component was localized
      to all three characteristics histopathologic lesions, namely, neurofibrillary
      tangles, senile plaques, and amyloid angiopathy. Furthermore, in cases with
      prominent staining of gray matter parenchymal lesions, intravascular staining was
      decreased. Given the fixation and processing methods used, amyloid P component
      was never seen to be localized to the cerebrovascular basement membrane. These
      data argue against amyloid P component's postulated role as the anchor for
      vascular beta-amyloid deposition. Because there is no evidence for intrinsic
      amyloid P component production in brain, its perivascular and parenchymal
      distributions suggest either compromise of the blood-brain barrier or transport
      across vascular endothelium.

PMID- 7714243
TI  - Differences in the connectivity of rat pudendal motor nuclei as revealed by
      retrograde transneuronal transport of wheat germ agglutinin.
AB  - Bilateral coordinated activation of pudendal motoneurons is an essential
      component of penile reflexes in male rats. However, little is known about the
      intraspinal organization of these reflexes. In the present study, retrograde
      transneuronal transport of wheat germ agglutinin (WGA) was used to examine the
      organization of spinal motoneurons and putative interneurons mediating penile
      reflexes in adult male rats. Injection of WGA into the ventral bulbospongiosus
      muscle resulted in direct retrograde labeling of motoneurons in the ipsilateral
      dorsomedial (DM) nucleus and transneuronal labeling of ipsilateral and
      contralateral DM motoneurons. Motoneurons in the ipsilateral and contralateral
      dorsolateral (DL) nuclei were not labeled. WGA-labeled putative interneurons were
      observed bilaterally, primarily in the ventromedial spinal gray matter extending
      dorsally to the central canal and the dorsal gray commissure. The number of
      transneuronally labeled putative interneurons increased with longer survival
      times. Injection of WGA into the ischiocavernosus muscle resulted in direct
      retrograde labeling of motoneurons in the medial subdivision of the ipsilateral
      DL nucleus. However, no WGA labeling was detected in motoneurons in the lateral
      subdivision of the ipsilateral DL nucleus, the contralateral DL nucleus, or the
      DM nuclei at any of the survival times studied (1-7 days). Only a small number of
      transneuronally labeled putative interneurons was observed in the ventrolateral
      gray matter at longer survival times (3-7 days). Thus, marked differences were
      observed between the DM and DL nuclei with respect to the transneuronal transport
      of WGA. These results are discussed with respect to the organization of the
      spinal circuits that mediate pudendal motor reflexes.

PMID- 7714242
TI  - Ultrastructural and immunocytochemical characterization of terminals of
      postsynaptic ascending dorsal column fibers in the rat cuneate nucleus.
AB  - The morphology, synaptic contacts, and neurotransmitter enrichment of
      postsynaptic dorsal column terminals in the cuneate nucleus of rats were
      investigated and compared with those of identified primary afferents. For this
      purpose, anterograde transport of horseradish peroxidase-based tracers injected
      in the spinal cord was combined with postembedding immunogold labeling for
      glutamate and gamma-aminobutyric acid (GABA). Anterogradely labeled postsynaptic
      dorsal column terminals were morphologically homogeneous: they were small (mean
      area = 1.37 microns 2) and dome-shaped, contacted single dendritic shafts or cell
      bodies, and were not involved in axoaxonic synapses. The majority of them were
      not enriched in glutamate or GABA immunoreactivity compared with other tissue
      components. Their morphology, size, and neurotransmitter content thus differed
      from that of primary afferents. These differences are consistent with distinct
      functional roles for the two main afferent systems ascending to the cuneate
      nucleus.

PMID- 7714244
TI  - Morphology of developing rat genioglossal motoneurons studied in vitro: relative
      changes in diameter and surface area of somata and dendrites.
AB  - This study describes the postnatal change in size of motoneurons in the
      hypoglossal nucleus that innervate the genioglossus muscle. Such anatomical
      information is essential for determining the cellular mechanisms responsible for
      the changes observed in the electrical properties of these motoneurons during
      postnatal development. The cells analyzed here are part of an earlier study
      (Nunez-Abades et al. [1994] J. Comp. Neurol. 339:401-420) where 40 genioglossal
      (GG) motoneurons from four age groups (1-2, 5-6, 13-15, and 19-30 postnatal days)
      were labeled by intracellular injection of neurobiotin in an in vitro slice
      preparation of the rat brainstem and their cellular morphology was reconstructed
      in three-dimensional space. The sequence of postnatal dendritic growth can be
      described in two phases. The first phase, between birth (1-2 days) and 13-15
      days, was characterized by no change in either dendritic diameter (any branch
      order) or dendritic surface area of GG motoneurons. However, maturation of the
      dendritic tree produced more surface area at greater distances from the soma by
      redistributing existing membrane (retracting some terminal branches). During the
      second phase, between 13-15 days and 19-30 days, the dendritic surface area
      doubled as a result of an increase in the dendritic diameter across all branch
      orders and a generation of new terminal branches. In contrast to the growth
      exhibited by the dendrites, there was little discernible postnatal growth of
      somata. At all ages, dendrites of GG motoneurons show the largest amount of
      tapering in the first-and second-order dendrites. The calculated dendritic trunk
      parameter deviated from a value 1.0, indicating that the dendritic tree of
      developing GG motoneurons cannot be modeled accurately as an equivalent cylinder.
      However, the value of this parameter increased with age. Strong correlations were
      found between the diameter of the first-order dendrite and the dendritic surface
      area, dendritic volume, combined dendritic length, and, to a lesser extent, the
      number of terminal dendrites in GG motoneurons. Correlations were also found
      between somal and dendritic geometry but only when data were pooled across all
      age groups. These data support earlier studies on kitten phrenic motoneurons,
      which concluded that postnatal growth of motoneurons was not a continuous
      process. Based on the fact that there was no growth in the first 2 weeks, the
      changes in the membrane properties described during this phase of postnatal
      development (e.g., decrease in input resistance) cannot be attributed to
      increases in the total membrane surface area of these motoneurons.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7714246
TI  - Expression of FGF-2 and FGF receptor type 1 in the adult rat brainstem: effect of
      colchicine.
AB  - In the adult rat brainstem, neuronal subpopulations of several motor and sensory
      nuclei display basic fibroblast growth factor (bFGF or FGF-2) immunoreactivity
      (IR; Grothe et al. J. Comp. Neurol. 305:328-336). In the present study we
      demonstrate that FGF-2-IR correlates with staining for the high-affinity FGF
      receptor 1. Intracerebroventricular injection of colchicine leads to the
      disappearance or substantial reduction of FGF-2-IR in the hypoglossal, facial,
      trigeminal motor, trochlear, and mesencephalic trigeminal nuclei. In contrast,
      FGF-2-IR appears in many perikarya of the red nucleus and the medial nucleus of
      the trapezoid body, whereas in control rats both nuclei showed immunostained
      fibers and almost no immunoreactive cell bodies. This dramatic change of FGF-2-IR
      could be explained by the ability of colchicine to block fast axonal transport.
      Cranial nuclei may internalize FGF-2 at the periphery via high-affinity receptors
      and retrogradely transport the molecule to their perikarya. The red nucleus and
      the medial nucleus of the trapezoid body may synthesize FGF-2 and provide the
      growth factor to afferent or efferent neurons. The presence of FGF-2 mRNA in
      brainstem extract and the absence of the FGF-2 transcript in extracts of the
      hypoglossal nucleus corroborate this suggestion. The effect of colchicine on FGF
      2-IR in the brainstem nuclei suggests that FGF-2 could be specifically
      retrogradely transported in other cranial nuclei, in addition to the hypoglossal
      system. Together with the ability of FGF-2 to stimulate neuronal survival, this
      result strongly supports the hypothesis that FGF-2 is acting as a neurotrophic
      factor on specific central neuron populations.

PMID- 7714248
TI  - Neurofilament sidearm proteolysis is a prominent early effect of axotomy in
      lamprey giant central neurons.
AB  - In the accompanying paper, it was shown that axotomy of lamprey spinal axons
      induces the rapid formation of condensed neurofilamentous masses in the proximal
      axon stump near the lesion. In this study, we used immunocytochemical and Western
      blot analysis to characterize these masses further and to determine the time
      course of their formation and dispersal. We show that monoclonal antibodies
      specific to the "rod" domain of lamprey neurofilament protein strongly stain such
      masses in tissue sections without staining other axonal neurofilaments.
      Antibodies specific for the neurofilament "sidearm" domain fail to recognize
      neurofilamentous masses but stain other axonal neurofilaments. Western blots of
      spinal cord segments from the lesion site were compared to unlesioned cord and to
      samples of cord distant from the lesion. We found that a neurofilament rod
      specific antibody identified breakdown products of the same size as the rod
      domain in samples from the lesion site, but not elsewhere. Other lesion-specific
      neurofilament breakdown products were recognized by a sidearm-specific antibody.
      This lesion-specific pattern of neurofilament proteolysis was visible at 1 day
      postlesion and was still present 3 weeks later. Immunocytochemistry showed masses
      of rod-staining neurofilaments in axon stumps by 12 hours postlesion that
      remained for 1-2 weeks postaxotomy; these dispersed with the onset of
      regeneration. Such neurofilament rod staining was also prominent in distal axon
      stumps undergoing Wallerian degeneration. We conclude that axotomy induces
      neurofilament sidearm proteolysis near the lesion, permitting antibody access to
      the rod domain. We suggest that sidearm loss causes the high packing density of
      neurofilaments within neurofilamentous masses near the lesion site and that
      neurofilament sidearm proteolysis can be used to distinguish degenerative from
      regenerative changes in lesioned lamprey axons.

PMID- 7714247
TI  - Early cytoskeletal changes following injury of giant spinal axons in the lamprey.
AB  - The spinal cord of the larval sea lamprey contains identified giant axons that
      readily regenerate following spinal transection. In this study, we used serial
      light and electron microscopy to analyze the early ultrastructural consequences
      of axotomy in the proximal stumps of these axons near the lesion site. Axotomy
      results in two types of striking ultrastructural changes: 1) changes associated
      with the degeneration of axoplasm and subsequent retraction of the cut axon from
      the lesion and 2) changes associated with the early stages of axonal
      regeneration. Degenerative changes include the disruption of mitochondria to form
      large vacuoles, the collapse of neurofilaments into closely packed masses
      (condensed filamentous cores; CFCs), and the appearance of amorphous electron
      dense bodies (dense granular masses; DGMs). Events associated with regeneration
      include the disappearance of vacuoles, DGMs, and CFCs and the appearance of
      small, sprout-like projections from the axon stump. Thus, we show that
      degenerative and regenerative events can be clearly separated from one another in
      identified axons, unlike the situation in the central nervous systems of amniote
      vertebrates such as mammals.

PMID- 7714249
TI  - Inputs from identified jaw-muscle spindle afferents to trigeminothalamic neurons
      in the rat: a double-labeling study using retrograde HRP and intracellular
      biotinamide.
AB  - Projections from physiologically identified jaw-muscle spindle afferents onto
      trigeminothalamic neurons were studied in the rat. Trigeminothalamic neurons were
      identified by means of retrograde transport of horseradish peroxidase from the
      ventroposteromedial nucleus of the thalamus. Labeled neurons were found
      contralaterally in the supratrigeminal region (Vsup), the trigeminal principal
      sensory nucleus, the ventrolateral part of the trigeminal subnucleus oralis, the
      spinal trigeminal subnuclei interpolaris and caudalis, the reticular formation,
      and an area ventral to the trigeminal motor nucleus (Vmo) and medial to the
      trigeminal principal sensory nucleus (AVM). Jaw-muscle spindle afferents were
      physiologically identified by their increased firing during stretching of the jaw
      muscles and intracellularly injected with biotinamide. Axon collaterals and
      boutons from jaw-muscle spindle afferents were found in Vmo; Vsup; the
      dorsomedial part of the trigeminal principal sensory nucleus (Vpdm); the
      dorsomedial part of the spinal trigeminal subnuclei oralis, interpolaris (Vidm)
      and caudalis; the parvicellular reticular formation (PCRt); and the mesencephalic
      trigeminal nucleus. Trigeminothalamic neurons in Vsup, Vpdm, Vidm, PCRt, and AVM
      were associated with axon collaterals and boutons from intracellularly stained
      jaw-muscle spindle afferents. Trigeminothalamic neurons in Vsup, Vpdm, Vidm, and
      PCRt were closely apposed by one to 14 intracellularly labeled boutons from jaw
      muscle spindle afferents, suggesting a powerful input to some trigeminothalamic
      neurons. These data demonstrate that muscle length and velocity feedback from jaw
      muscle spindle afferents is projected to the contralateral thalamus via multiple
      regions of the trigeminal system and implicates these pathways in the projection
      of trigeminal proprioceptive information to the cerebral cortex.

PMID- 7714245
TI  - Neuronal and nonneuronal expression of neurotrophins and their receptors in
      sensory and sympathetic ganglia suggest new intercellular trophic interactions.
AB  - Nerve growth factor promotes the survival of populations of sensory and
      sympathetic neurons. Although ganglia have been used for classical assays of
      neurotrophin action, knowledge is incomplete regarding the spatial arrangements
      through which neurotrophins are delivered to responsive cells within the ganglia
      and their attached nerve trunks. Whereas populations of ganglionic neurons may be
      capable of responding to a particular neurotrophin in vitro, the spectrum of
      receptor components and neurotrophins expressed by the various neuronal and
      nonneuronal cells comprising the ganglia in adult rats remains to be elucidated
      in vivo. Brain-derived neurotrophic factor (BDNF) mRNA was expressed by a
      population of small to medium sized neurons in all sensory ganglia except in the
      mesencephalic nucleus of the trigeminal nerve. Interestingly, BDNF
      immunoreactivity was detected in a more widespread population of neurons of these
      ganglia, as well as in scattered satellite cells of both sensory and sympathetic
      ganglia. These nonneuronal cells also expressed mRNA encoding a truncated form of
      the BDNF receptor, trkBtrunc, and full-length transcripts of trkB appeared to be
      confined to neuronal populations. Several other components of neurotrophin
      receptors (low-affinity neurotrophin receptor, trk, and trkC) were prominently
      expressed by different populations of neuronal cells in sympathetic and sensory
      ganglia, but they were not detected in nonneuronal cells. Neither nerve growth
      factor nor neurotrophin-3 mRNAs were detected in these ganglia. Unexpectedly,
      BDNF and trkBtrunc expression was detected in oligodendrocytes myelinating the
      central processes of sensory neurons. Schwann cells did not express detectable
      quantities of either entity, thereby establishing a dramatic boundary delineated
      by neurotrophin/neurotrophin receptor expression that coincided with the
      interface between the oligodendroglia of the central nervous system (CNS) and
      Schwann cells of the peripheral nervous system (PNS). Localization of BDNF
      expression to an additional population of nonneuronal cells--satellite cells
      within sensory and sympathetic ganglia--suggest a more extensive role for
      neurotrophic factors than originally encompassed by the target-derived
      neurotrophic-factor-concept paradigm. These data support the hypothesis of a
      possible autocrine or paracrine trophic interaction between populations of
      neuronal and nonneuronal cells in the peripheral nervous system. BDNF expression
      in oligodendrocytes but not in Schwann cells at the CNS/PNS junction may provide
      an additional means of maintaining cell-appropriate connections in the nervous
      system.

PMID- 7714250
TI  - Distribution of neurotensin-containing neurons in the central nervous system of
      the dog.
AB  - The distribution of neurotensin-containing cell bodies and fibers was examined in
      the central nervous system of the dog using light microscopic
      immunohistochemistry. A very large population of neurotensin-containing cell
      bodies was observed in the septal nuclei, nucleus accumbens septi, preoptic
      areas, bed nucleus of the stria terminalis, olfactory tubercle, entorhinal
      cortex, ventral subiculum, anterodorsal thalamic nucleus, anteroventral thalamic
      nucleus, nucleus reuniens, lateral habenular nucleus, parabrachial nucleus, and
      nucleus of the solitary tract. Extremely dense networks of neurotensin-containing
      fibers were found in the globus pallidus, hypothalamus, infundibular stalk,
      ventral tegmental area, periaqueductal gray, interpeduncular nucleus, and spinal
      nucleus of the trigeminal nerve and substantia gelatinosa. However, the cerebral
      neocortex and cerebellum were negative for neurotensin in the present study. When
      the present findings are compared with those in other animals, it is clear that
      the major species-specific differences in distribution involve three
      immunonegative regions and four immunopositive regions in the dog: The former are
      the cerebral neocortex, mammillary body, and hippocampus; the latter are the cell
      bodies in the pyramidal layer of the olfactory tubercle, the superficial and
      middle layers of the entorhinal cortex and ventral subiculum, and the nerve
      fibers in the interpeduncular nucleus. The present study indicates a rather
      extensive network of neurotensin neurons in the central nervous system of the
      dog.

PMID- 7714252
TI  - Correlation of axon projections and peptide immunoreactivity in mesocerebral
      neurons of the snail Helix aspersa.
AB  - The purpose of this investigation was to elucidate the organization of efferent
      neurons in the mesocerebrum of a terrestrial snail. The mesocerebrum is one of
      three regions, or lobes, that can be identified by gross inspection. Previous
      studies have indicated a possible function for the mesocerebrum in the control of
      mating behavior. We used both anterograde and retrograde tracing methods to
      determine the axon projections of mesocerebral neurons. Virtually all the neurons
      (96%) send an axon into the cerebropedal connective nerve, and about 25% of these
      fibers continue into the nervus cutaneous pedalis primus dexter, which innervates
      the dart sac. Many neurons have additional axon branches in other nerves,
      especially the penial nerve, which receives projections from about 25% of
      mesocerebral cells. Neurons that are backfilled from the nervus cutaneus pedalis
      primus dexter are predominantly immunoreactive for FMRF amide, whereas neurons
      that are backfilled from the penial nerve are predominately immunoreactive for
      APGWamide. These results suggest a functional association between FMRFamide and
      dart shooting on the one hand, and between APGWamide and penial eversion on the
      other. Some cells contain both APGWamide and FMRFamide; these cells may have dual
      projections in both the penial nerve and the nervus cutaneous pedalis primus
      dexter.

PMID- 7714251
TI  - Subcompartmental organization of the ventral (protrusor) compartment in the
      hypoglossal nucleus of the rat.
AB  - The extent and myotopic organization of the ventral (protrusor) compartment of
      the hypoglossal nucleus (nXII) in the rat is controversial. Of particular concern
      is the location of motoneurons that innervate the intrinsic (verticalis,
      transversus) as compared to extrinsic (genioglossus) tongue protrusor muscles.
      These issues were investigated with retrograde transport,
      lesion/degeneration/immunocytochemical, and classic Golgi staining techniques.
      Results from these experiments demonstrate the following: (1) the ventral
      compartment extends the entire rostrocaudal length of nXII and is organized into
      three longitudinally oriented subcompartments, one medial and one lateral within
      the boundaries of nXII, and one outside the confines of nXII, defined as the
      lateral accessory subcompartment; 2) the medial and lateral subcompartments
      contain motoneurons that innervate the intrinsic (verticalis, transversus) and
      extrinsic (genioglossus) tongue protrusor muscles, respectively, while the
      lateral accessory subcompartment innervates the geniohyoid muscle; (3) ventral
      subcompartments are unequal in size and vary along the rostrocaudal dimension of
      nXII. The medial subcompartment is largest caudally and smallest rostrally, while
      the converse is true for the lateral subcompartment. By contrast, the lateral
      accessory subcompartment is present only along the caudal one-half of nXII; (4)
      medial and lateral subcompartments are further organized into smaller subgroups.
      Medial and centromedial subgroups are discernible within the medial
      subcompartment, lateral and centrolateral subgroups within the lateral
      subcompartment. Both medial and lateral subgroups extend throughout the
      rostrocaudal length of nXII, whereas the centromedial and centrolateral subgroups
      are present only along the middle two-thirds of nXII where they form a central
      motoneuron band; (5) there is an inverse myotopic organization within the medial
      and lateral subcompartments such that proximal and distal portions of intrinsic
      and extrinsic protrusor muscles receive innervation from rostral and caudal
      motoneurons, respectively; and (6) there is a correlation between motoneuron
      morphology (size, shape and dendritic field domains), subcompartment
      localization, and myotopic specificity. Motoneurons in the medial subcompartment
      are small (mean = 23.08 microns), round to globular, with dendrites oriented
      medially, dorsomedially, dorsolaterally, and caudally, whereas lateral
      subcompartment motoneurons are large (mean = 29.49 microns), round to triangular,
      with dendrites directed mainly mediolaterally and dorsally. These data are
      relevant to understanding the functional organization of nXII and the motor
      control of the tongue. Results are further discussed relative to the convergence
      of multifunctional afferent systems in the ventromedial subcompartment of nXII.

PMID- 7714253
TI  - Acoustic classification of the state of artificial heart valves.
AB  - Transthoracic acoustic signals from BSCC (Bjork-Shiley convexo-concave)
      mechanical heart valves implanted in human patients were processed to determine
      if the valves had separated outflow struts. For normal valves with intact outflow
      struts it is demonstrated that a time-windowed spectral analysis reveals the
      resonant frequency of the vibrating strut. The strut, which is set into vibration
      when the valve closes during each cardiac cycle, has a resonant frequency that
      varies among valves but usually is between 7000 and 8000 Hz. The signal
      processing technique is based on the hypothesis that the strut's resonant
      waveform has a smaller decay rate than interfering signals and noise generated
      upon closure by other mechanical components of the valve. A time window can be
      selected that optimizes the outflow strut's signal-to-interference ratio. It is
      shown that the absence of the resonant frequency in the 7000- to 8000-Hz interval
      is an indication that one of the strut's legs has separated from the valve's
      flange. This separation of one leg appears to precede the valve's failure that
      occurs if the other leg also separates from the flange, a state referred to as
      OSF (outlet strut failure). Acoustic data recorded from 18 clinical patients with
      implanted valves, that were later explanted and examined, formed the database for
      this study. Of the 18 valves 9 were SLS (single-leg separated) and 9 were intact
      (both legs of the outflow strut still attached to the valve's flange). The time
      windowed spectral process correctly identified the states of all 18
      valves.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714254
TI  - Dependence of distortion-product otoacoustic emissions on primary levels in
      normal and impaired ears. I. Effects of decreasing L2 below L1.
AB  - The 2f1-f2 distortion-product otoacoustic emission (DPOAE) is evoked by two
      primary tones of frequencies f1 < f2, and levels L1 and L2. Previous reports
      indicate that decreasing L2 below L1 = L2 can; (1) increase DPOAE amplitude in
      normal ears, and (2) increase the degree to which DPOAE amplitudes are reduced by
      cochlear trauma. Although both of these factors could be advantageous for
      clinical applications of DPOAEs, neither has been explored in detail. In the
      present study, 2f1-f2 DPOAE-amplitude frequency functions were collected from
      normal and impaired ears of rabbits and humans, with L1 = L2, and with L2 < L1,
      at each of three values of L1. In rabbits, controlled tonal or noise
      overexposures were used to produce permanent reductions of DPOAE amplitudes.
      Comparison of pre- and postexposure DPOAE-amplitude frequency functions
      demonstrated that the frequency-specific reductions of DPOAEs were enhanced by
      decreasing L2 below L1. In humans, DPOAE-amplitude frequency functions obtained
      with the various L1 and L2 combinations were collected from 16 normal ears to
      provide preliminary normative data for each stimulus-level condition. The L1-L2
      that produced the maximum DPOAE amplitude in normal ears was systematically
      dependent on L1. Thus at most frequencies, decreasing L2 below L1 = L2
      substantially reduced mean DPOAE amplitude when L1 > or = 75 dB SPL, but
      increased mean DPOAE amplitudes at L1 = 65 dB SPL. However, the increase of mean
      DPOAE amplitude obtained by decreasing L2 below L1 = 65 dB SPL was small, being
      less than 3.5 dB at most frequencies. More importantly, at L1 = 65 dB SPL, L2
      could be decreased considerably below L1 = L2 without reducing mean DPOAE
      amplitude relative to that at L1 = L2. Inspection of DPOAE-amplitude frequency
      functions obtained from subjects with mild or moderate sensorineural hearing
      losses indicated that, in frequency regions of hearing impairment, decreasing L2
      below L1 can enhance the degree of reduction of DPOAEs below the corresponding
      normative amplitudes, without reducing the normative amplitude. It is concluded
      that decreasing L2 below L1 = L2 has the potential to enhance the performance of
      DPOAEs in clinical applications.

PMID- 7714255
TI  - Dependence of distortion-product otoacoustic emissions on primary levels in
      normal and impaired ears. II. Asymmetry in L1,L2 space.
AB  - Previous studies indicate that the amplitude of 2f1-f2 distortion-product
      otoacoustic emissions (DPOAEs), evoked by two tones of frequencies f1 < f2,
      demonstrates a complex dependence on the levels (L1 and L2) of the primary tones.
      In the present study, 2f1-f2 DPOAE amplitudes were measured over a wide range of
      L1 and L2 in normal human ears, allowing a systematic, level-dependent asymmetry
      of DPOAE amplitude in L1,L2 space to be characterized. The L1,L2 at which DPOAEs
      were largest was close to L1 = L2 at high stimulus levels, but moved
      monotonically toward L1 > L2 as stimulus levels decreased. A related observation
      was that DPOAE amplitude had a greater dependence on L1 and on L2. These
      asymmetries were quantified in normal human ears, and compared to the
      corresponding asymmetries apparent in data from animal models. Recent studies
      have demonstrated that the reduction of DPOAE amplitude by cochlear trauma is
      greater when L1 > L2 than when L1 = L2, suggesting that the reduction of DPOAEs
      by trauma demonstrates an asymmetry in L1,L2 space that is qualitatively similar
      to that of normative DPOAE amplitude. To investigate this issue, 2f1-f2 DPOAE
      amplitudes were measured over a wide range of L1 and L2 in rabbit ears pre- and
      postinjection of the ototoxic loop-diuretic ethacrynic acid. The results indicate
      that the asymmetry in L1,L2 space of the reduction of DPOAEs by trauma is both
      qualitatively and quantitatively similar to the asymmetry in L1,L2 space of
      normative DPOAE amplitude. Specifically, the L1 values that maximized normative
      DPOAE amplitudes for any specified L2 (or, equivalently, the L1 values that
      allowed L2 to be minimized for any specified normative DPOAE amplitude) also
      yielded the greatest reduction of DPOAEs by the diuretic. In humans, the L1
      values that maximize normative DPOAE amplitudes for any specified L2 are well
      approximated by a simple equation, with parameters that vary with frequency and
      f2/f1. It is suggested that the L1,L2 values defined by this equation may be
      optimum for use in clinical applications.

PMID- 7714256
TI  - Responses of dorsal cochlear nucleus single units to electrical pulse train
      stimulation of the auditory nerve with a cochlear implant electrode.
AB  - In response to 100-ms duration electrical stimulation within the range 50-400
      pulses per second (pps), and at 1.6- to 2.4-mA stimulus current, a range of
      poststimulus time histogram (PSTH) patterns were observed from dorsal cochlear
      nucleus (DCN) units, they were usually primarylike, onset or "negative response"
      and occasionally buildup or pauser patterns. It appeared that the excitatory and
      suppressive processes, also termed neural drives, in response to 2.5-pps
      electrical stimulation were the main determinants of DCN unit responses to 50- to
      400-pps stimulation. This was demonstrated by a model of DCN responses to
      electrical stimulation of the auditory nerve. The neural drives required to model
      the PSTH patterns were (i) an excitatory process with a latency of < 5 ms, (ii) a
      second excitatory process latency of 4.5-10 ms, (iii) a long acting suppressive
      process with a latency of < 15 ms and a duration of > 70 ms, (iv) a short acting
      suppressive response with a latency of 2.5-3.7 ms and a duration usually < 5 ms,
      but always < 20, and (v) a drive contributing spontaneous activity to the unit.
      In addition to these processes which were observed at 2.5 pps, an additional,
      transient suppressive process was postulated to operate only at 50-400 pps. It
      was postulated that the PSTH patterns observed were due to differences in the
      strengths of these drives between units.

PMID- 7714257
TI  - Frequency contribution to the click-evoked auditory brain-stem response in human
      adults and infants.
AB  - The results of previous research reports have led some investigators to
      hypothesize that frequency contribution to the infant click-evoked auditory brain
      stem response (ABR) is low-frequency dominated and derived primarily from the
      apical cochlea. This is in contrast to latency and morphology of the adult click
      evoked ABR which reflects contributions from the basal cochlea. Recent research,
      however, has suggested that a simple low-frequency first model of development
      does not adequately describe the infant auditory brain-stem response. This
      experiment was conducted as a carefully controlled comparison of infant and adult
      click-evoked ABRs restricted to narrow frequency ranges with notched-noise
      masking. The primary objective of this experiment was to define frequency
      contribution to wave I and V click-evoked ABR latency and morphology in adults
      and 3-month-old infants. Results indicate that 3-month-old infants have adultlike
      latency shifts (re: unmasked latency) when the ABR is recorded in the presence of
      notched-noise masking with center frequencies ranging from 500-8000 Hz. With high
      frequency centered notches, latency, and morphology change are similar to the
      unmasked response, while low-frequency centered notches induce an average latency
      shift of approximately 3.5 ms for wave I and V of both infant and adult subjects.
      These data suggest that by 3 months of age, in normal hearing infants, ABR
      latency and appearance are determined by high-frequency spectral components in
      the broadband click which activate the basal cochlea. The adultlike pattern of
      latency shift observed in the ABR of these infants suggests that relatively
      mature tonotopic organization is established by 3 months of age.

PMID- 7714258
TI  - A computer model of dorsal cochlear nucleus pyramidal cells: intrinsic membrane
      properties.
AB  - Manis [P. B. Manis, J. Neurosci. 10, 2338-2351 (1990)] studied "simple spiking,"
      pyramidal cells of the dorsal cochlear nucleus (DCN) maintained in vitro.
      Response profiles to hyperpolarizing and depolarizing current pulses were
      generated. Hyperpolarization of the cell membrane followed by depolarization
      produced markedly different response profiles from those generated when no
      prehyperpolarization was imposed. By manipulating the magnitude of the
      hyperpolarizing and depolarizing pulses, "chopper," "pauser" and "build-up"
      response patterns, similar to those in vivo, could be generated by individual
      cells. Manis concluded that the different response profiles resulted from the
      modulation of intrinsic membrane conductances by the prehyperpolarizing pulses.
      Here a computer model is used to show that (a) steady-state hyperpolarization can
      influence cell responding to subsequent depolarization in a manner consistent
      with the data reported by Manis; and (b) the effects reported can be generated by
      the addition of a modeled transient potassium conductance to the standard Hodgkin
      Huxley model of spike generation [A. L. Hodgkin and A. F. Huxley, J. Physiol.
      117, 500-544 (1952)]. The model will be of use to those who wish to consider the
      role of various excitatory and inhibitory inputs to pyramidal cells and to
      establish their functional role within the DCN.

PMID- 7714259
TI  - Interspike intervals as a correlate of periodicity pitch in cat cochlear nucleus.
AB  - Amplitude modulated (AM) signals have often been used as precisely defined
      partial analogs of speech sounds. This study considers the response to an AM
      complex with 200% sinusoidal modulation, that is, the amplitudes of the three AM
      components are equal. By varying the carrier frequency across the entire
      frequency range of unit response, it is shown that units in the cochlear nucleus
      of cat are relatively insensitive to variation in the carrier frequency, which is
      to say that population response to an AM signal at a fixed locus will be
      widespread. These stimuli and procedures result in the presentation of both
      harmonic and inharmonic complexes, and thus permit assessment of neural responses
      for the information needed to make spectral or time-domain pitch matches. It is
      shown that the reciprocals of the modes (favored intervals) in the interspike
      interval histogram reflect the first effect of pitch shift, which is defined
      psychophysically as a proportional shift in pitch to the change in carrier
      frequency. In particular, interspike intervals of units with a widespread
      spectral response provide a basis to explain phase and dominant component pitch
      behavior that early narrow-band pitch theories found problematical. The amplitude
      of phase locking to individual AM components varies systematically though there
      are some unexplained variations across the frequency-intensity plane that could
      be due to combination tones. The unit response to a quasifrequency modulated
      (QFM) stimulus shows that if pitch is based on interspike intervals, it would
      remain the smae as pitch for an AM signal. The magnitude of the synchrony
      response to QFM stimuli is less than to AM stimuli for the majority of cochlear
      nucleus units; however, there are exceptions.

PMID- 7714261
TI  - The perception of frequency peaks and troughs in wide frequency modulations. II.
      Effects of frequency register, stimulus uncertainty, and intensity.
AB  - In widely frequency modulated sine tones, frequency maxima are perceived more
      accurately than frequency minima: A shift in a local frequency extremum is better
      detected when the extremum is a maximum than when it is a minimum, even within
      the same spectral region [L. Demany and K. I. McAnally, J. Acoust. Soc. Am. 96,
      706-715 (1994)]. It is reported here that this perceptual asymmetry is about
      equally strong for frequency extrema near 250 and 1000 Hz, but weaker near 4000
      Hz. It was also found that near 1000 Hz, the asymmetry is about equally strong
      for stimuli with an SPL of 35 and 70 dB, although the neural excitation patterns
      of a 1000-Hz tone probably have a different shape--and more specifically a
      different asymmetry--at these two levels. Finally, stimulus uncertainty was found
      to reduce the perceptual asymmetry: A weaker asymmetry was measured when the
      standard frequency extremum varied randomly from trial to trial than when it was
      fixed. The latter result, and the fact that the asymmetry did not decrease with
      training in the discrimination task, suggest that the asymmetry cannot be
      counteracted by "top-down" attentional processes and may be a preattentional
      phenomenon.

PMID- 7714263
TI  - Effects of carrier frequency, modulation rate, and modulation waveform on the
      detection of modulation and the discrimination of modulation type (amplitude
      modulation versus frequency modulation).
AB  - Initially, psychometric functions were measured for the detection of amplitude
      modulation (AM) or frequency modulation (FM), using a two-alternative forced
      choice (2AFC) task. Carrier frequencies were 125, 1000, and 6000 Hz, and
      modulation rates were 2, 5, and 10 Hz. For the two lower carrier frequencies, FM
      detection tended to be best at the lowest modulation rate while AM detection was
      best at the highest rate. For the 6000-Hz carrier, both AM and FM detection
      tended to be poorest at the lowest modulation rate. Then, pairs of values of AM
      and FM were selected that would be equally detectable, and psychometric functions
      were measured for the discrimination of AM from FM, again in a 2AFC task. For
      carrier frequencies of 125 and 1000 Hz, the ability to discriminate AM from FM
      was always poorest at the highest modulation rate (10 Hz); at this rate some
      subjects were essentially unable to discriminate AM from FM when the
      detectability of the modulation was relatively low (d' of 1.16 and below). For a
      modulation rate of 2 Hz, and when the detectability of the modulation was
      moderate (d' up to about 2), some subjects discriminated the type of modulation
      rate varied across subjects, but there was still a trend for poorer
      discrimination of modulation type at the highest modulation rate. It is suggested
      that FM detection at a 10-Hz modulation rate is based largely on changes in
      excitation level for all carrier frequencies. For a 2-Hz modulation rate, and for
      the two lowest carrier frequencies, an extra mechanism, possibly based on phase
      locking, may play a role in the detection and discrimination of FM. This
      mechanism may be ineffective at modulation rates above about 5 Hz because the
      stimuli spend insufficient time at frequency extremes. To check on this,
      psychometric functions were measured for the detection of FM and AM using
      quasitrapezoidal modulation with a rate of five periods per second and carriers
      of 250, 1000, and 6000 Hz. This produced improvements in performance relative to
      that obtained with 5-Hz sinusoidal modulation and, for the two lower carrier
      frequencies only, the improvements were markedly greater for FM than for AM
      detection. This is consistent with the idea that the use of of phase-locking
      information depends on the time that the stimuli spend at frequency extremes.

PMID- 7714262
TI  - Masked level discrimination: deterring profile listening.
AB  - Two experiments examined how level discrimination (also called intensity
      discrimination) between two successive three-tone complexes depends on the
      bandwidth and rove range of a notched-noise masker. The three-tone complex
      consisted of equally intense components at 0.84, 1, and 1.17 kHz set to 25, 55,
      or 85 dB SPL. The notch extended from 0.77 to 1.27 kHz for all masker bandwidths.
      The masker level changed randomly on each presentation to reduce profile cues.
      Results from five listeners showed that level-discrimination thresholds, delta
      L's (= 20 log([p + delta p]/p), where p is pressure), increased somewhat as the
      rove range increased. In contrast to profile-discrimination experiments, the
      delta L's did not decrease with increasing masker bandwidth. In addition, when
      the rove range was 10 dB or larger, discrimination was generally better than the
      best possible performance by a profile observer. The results indicate that
      profile analysis is not essential for reasonably good level discrimination in the
      presence of notched-noise maskers.

PMID- 7714264
TI  - Frequency discrimination as a function of frequency, measured in several ways.
AB  - Frequency discrimination was measured for a wide range of center frequencies
      (0.25-8 kHz) using three different tasks. In the first (difference limens for
      frequency, DLFs) subjects were required to indicate which of two successive tone
      pulses was higher in frequency. In the second (difference limens for change,
      DLCs), two successive pairs of tone pulses were presented; one pair had the same
      frequency and the other pair differed in frequency. Subjects were required to
      indicate which pair differed in frequency. In the third (frequency-modulation
      difference limens, FMDLs), subjects were required to indicate which of two
      successive tone pulses was frequency modulated. Modulation rates were 2, 5, or 10
      Hz. For frequencies up to 2 kHz, DLFs and DLCs were small (less than 0.6% of the
      center frequency) and were similar to one another. For frequencies of 4 kHz and
      above, both DLFs and DLCs increased markedly, but the increase was greater for
      DLFs. Thus the worsening of performance at high frequencies is greater when
      subjects are required to indicate the direction of a frequency change than when
      they just have to detect any change. FMDLs, when expressed relative to the
      carrier frequency, varied much less with frequency than DLFs or DLCs. At 2 kHz
      and below, FMDLs were larger than DLFs or DLCs. Above 4 kHz, FMDLs were smaller
      than DLFs or DLCs. At 2 kHz and below, FMDLs usually worsened with increasing
      modulation frequency. Above 4 kHz, FMDLs improved with increasing modulation
      frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714260
TI  - Masked thresholds and consonant recognition in low-pass maskers for hearing
      impaired and normal-hearing listeners.
AB  - Thresholds and consonant recognition were measured in six low-pass maskers as a
      function of masker bandwidth for hearing-impaired subjects and for normal-hearing
      subjects listening in spectrally shaped broadband noise (SSBB). SSBB was adjusted
      such that thresholds in that masker for a normal-hearing listener were equal to a
      hearing-impaired listener's absolute thresholds. Thresholds measured in low-pass
      maskers were higher for hearing-impaired than for normal-hearing subjects for
      signal frequencies both within and outside masker passbands, although threshold
      differences were larger for signal frequencies outside masker passbands. Slopes
      of functions relating consonant recognition to speech level were not
      significantly different between groups, due to the presence of SSBB for the
      normal-hearing listeners. However, 25% of observed scores for hearing-impaired
      listeners, compared to only 5% of observed scores for normal-hearing listeners,
      were significantly poorer than predicted by the articulation index (AI), when AIs
      were computed using subjects' absolute thresholds. Better correspondence between
      observed and predicted scores in low-pass maskers was achieved when AIs were
      derived empirically from thresholds measured in each low-pass masker. Hence
      poorer-than-predicted consonant recognition scores in low-pass maskers were
      accounted for by higher-than-normal thresholds in those maskers.

PMID- 7714265
TI  - Modulation detection interference using random and sinusoidal amplitude
      modulation.
AB  - The detection of amplitude modulation (AM) of a target sound is made more
      difficult by the presence of a modulated sound some spectral distance from the
      target. This effect (modulation detection interference, or MDI) was examined for
      stimuli with random amplitude modulations (RAM) and for sounds with sinusoidal
      amplitude modulations (SAM) as a function of average modulation depth (m) of the
      interferer. In an experiment comparing comodulated and independent RAM targets
      and interferers, the amount of interference was not related to the modulation
      coherence of the target and interferer. Elevations in AM threshold increased as a
      function of m in a similar way for both conditions. The MDI for RAM and SAM
      targets and interferers was also compared. While no difference was found for AM
      detection of RAM and SAM, MDI was found to be greater for the RAM stimuli than
      for the SAM stimuli. A subsidiary experiment comparing RAM and SAM modulation
      depth discrimination indicated that RAM discrimination is more difficult than SAM
      discrimination. Taken together, these results are quantitatively consistent with
      a mechanism resembling AM discrimination as the underpinning of MDI in conditions
      where the target and interferer are synchronously gated.

PMID- 7714266
TI  - Modulation discrimination interference for narrow-band noise modulators.
AB  - The discrimination of the depth of amplitude modulation of a signal carrier
      frequency can be disrupted by the presence of other modulated carriers (maskers),
      an effect called modulation discrimination interference (MDI). This paper
      examines whether MDI is influenced by the similarity in the envelope pattern of
      the signal and masker. A narrow-band noise (centered at 10 Hz) was used as the
      signal modulator. The first experiment used masker modulators that were narrow
      band noises identical in spectral characteristics to the signal modulator. The
      masker modulators were either identical to the signal modulator, negatively
      correlated with it, or uncorrelated with it. The amount of MDI was similar for
      all three cases. In experiment 2, the masker was sinusoidally modulated at rates
      varying from 2 to 64 Hz. The results showed a broad tuning for modulation rate,
      comparable to that found for sinusoidal modulation of the signal. The maximum
      amount of MDI produced by the sinusoidally modulated masker was similar to that
      produced by the noise-modulated maskers when modulation depths were expressed as
      their root-mean-square values. It is concluded that similarity of the moment-by
      moment envelope pattern of the signal and masker modulators plays only a minor
      role in MDI, although similarity in modulation rate has some influence.

PMID- 7714267
TI  - Evaluation of a portable two-microphone adaptive beamforming speech processor
      with cochlear implant patients.
AB  - A two-microphone noise reduction technique was tested with four cochlear implant
      patients. The noise reduction technique, known as adaptive beamforming (ABF),
      used signals from only two microphones--one behind each ear--to attenuate sounds
      not arriving from the direction directly in front of the patient. The algorithm
      was implemented in a portable digital signal processor, and was compared with a
      strategy in which the two microphone signals were simply added together (two
      microphone broadside strategy). Tests with the four patients were conducted in a
      soundproof booth with target speech arriving from in front of the patient and
      multitalker babble noise arriving at 90 deg to the left. Results at 0-dB signal
      to-noise level (S/N) showed large improvements in speech intelligibility for all
      patients, when compared to the two-microphone broadside strategy. Precautions
      were taken to avoid cancellation of the target speech, and, accordingly,
      subjective tests showed no deterioration in performance for the adaptive
      beamformer in quiet. Physical measurement of the directional characteristics of
      the ABF was made with the microphones placed behind the ears of a KEMAR manikin
      and in the same acoustic environment as used with the patients. Results showed
      directional gain of approximately 10 dB when the angle of incidence for
      interfering noise was shifted more than 20 to 30 deg from directly in front of or
      behind the manikin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714268
TI  - The effect of gas density on glottal vibration and exit jet particle velocity.
AB  - Although theoretical studies include a term for gas density in their mathematical
      descriptions of glottal aerodynamics, the effect of gas density on glottal
      vibration has not been examined empirically. In this study, an in vivo canine
      model was used to evaluate the effect of gas density on glottal vibration by
      comparing phonation with air and helium. With gas flow and nerve stimulation held
      constant, phonation with helium resulted in an increased exit jet particle
      velocity for helium (45 m/s) compared to air (34 m/s). However, the measured
      increase in helium velocity was less than predicted by a proportional
      relationship between transglottal pressure and dynamic pressure. This difference
      could be due to a change in the constant of proportionality or in the dynamic
      pressure loss coefficient associated with the use of helium.

PMID- 7714269
TI  - A nonlinear dynamical systems analysis of fricative consonants.
AB  - Acoustic waveforms of the strident fricatives /s/, /z/, /integral of/, and /3/
      spoken by two native American English speakers are analyzed using modern chaotic
      analysis techniques. Fricative data are extracted from both intervocalic and
      sustained utterances. For comparison, acoustic waveforms of the vowels /a/, /i/,
      and /u/ are also analyzed. For 44% of the unvoiced fricative tokens in VCV
      contexts and 59% of the sustained voiced fricatives, indications of low
      dimensional dynamics could be found with the given limitations of stationarity.
      The low-dimensional chaotic behavior is exhibited by a correlation dimension (D2)
      ranging between 3 and 7.2, and by positive maximum Lyapunov exponents (LEs). For
      the remaining fricatives, results suggest that the dimensional complexity therein
      is greater than the maximum D2 value that could be reliably estimated from the
      available data (about 7.8 for the intervocalic cases and 9 for the sustained
      cases). Intervocalic voiced fricatives are excluded from the analysis due to
      stationarity requirements. Analysis of vowels, on the other hand, indicates
      nonchaotic behavior demonstrated by folded limit cycles and nonpositive maximum
      LEs; this is consistent with results of previous studies. Findings are
      interpreted in terms of posited articulatory and aerodynamic parameters of
      turbulence in the production of fricative consonants.

PMID- 7714270
TI  - Minimizing the effect of period determination on the computation of amplitude
      perturbation in voice.
AB  - Current methods of computing amplitude perturbation present in human voices
      depend upon being able to accurately determine fundamental period. In this paper,
      two methods of estimating the amplitude perturbation present in human voices,
      which do not depend on accurate determination of the boundaries between
      fundamental periods, are described. In both of these methods, amplitude
      perturbation is computed as the variance of an ensemble of periods calculated
      after these periods have been aligned in time. In one method, time alignment is
      accomplished using zero-phase transformation. In the second method, an
      unconstrained dynamic programming procedure is used. The accuracy of estimating
      amplitude perturbation by these two methods is evaluated using synthetic and
      natural voice signals and is also compared with an estimation using zero-padding
      based time alignment. The unconstrained dynamic programming method is shown to
      provide accurate estimation of voice amplitude perturbation over a variety of
      signal conditions.

PMID- 7714272
TI  - The perception of English and Spanish vowels by native English and Spanish
      listeners: a multidimensional scaling analysis.
AB  - A group of Spanish- and English-speaking listeners participated in a
      multidimensional scaling (MDS) study examining perceptual responses to three
      Spanish and seven English vowels. The vowel stimuli represented tokens of Spanish
      /i/, /e/, and /a/ and English /i/, /I/, /eI/, /epsilon/, /ae/, /lambda/, and /a/.
      Each vowel had been spoken by three monolingual talkers of Spanish or English and
      all possible vowel pairs (405 pairs) were presented to listeners (excluding pairs
      representing the same vowel category). Thirty monolingual English listeners and
      thirty native Spanish listeners who had learned English as a second language
      rated these vowel pairs on a nine-point dissimilarity scale. These perceptual
      distances were then analyzed using then individual-differences version of ALSCAL.
      Results demonstrated that the English monolinguals used three underlying
      dimensions in rating vowels while the Spanish-English bilinguals used just two.
      The most salient perceptual dimension for both groups distinguished vowel height.
      However, for the English listeners, this dimension was most significantly
      correlated with duration and indicated a language-dependent sensitivity to this
      phonetic feature. The second dimension for the English listeners represented a
      front-back distinction, while the third reflected a central/noncentral
      distinction. For the Spanish listeners, the second dimension was less easily
      interpreted. However, the perceptual data for the Spanish listeners was more
      interpretable in terms of the distribution of the vowels in the two-dimensional
      perceptual plane. The vowels were distributed in terms of three separate vowel
      clusters, each cluster near the location of a Spanish vowel.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7714271
TI  - Intrinsic F0 of vowels in the babbling of 6-, 9-, and 12-month-old French- and
      English-learning infants.
AB  - In every language so far examined, high vowels such as [i] and [u] tend to have
      higher fundamental frequencies (F0s) than low vowels such as [a]. This intrinsic
      F0 effect (IF0) has been found in the speech of children at various stages of
      development, except in the one previous study of babbling. The present study is
      based on a larger set of utterances from more subjects (six French- and six
      English-learning infants), at the ages 6, 9, and 12 months. It is found, instead,
      that IF0 appears even in babbling. There is no indication in these data of a
      developmental trend for the effect, and no indication of a difference due to the
      target language. These results support the claim that IF0 is an automatic
      consequence of producing vowels.

PMID- 7714273
TI  - Perception of voicing for syllable-initial stops at different intensities: does
      synchrony capture signal voiceless stop consonants?
AB  - In response to stop consonants with longer F1-cutback duration, the dominant
      synchronization of mid- and high-CF chinchilla auditory-nerve fibers changes from
      frequencies near F2 to frequencies near F1 at onset of voicing [D. G. Sinex and
      L. P. McDonald, J. Acoust. Soc. Am. 85, 1995-2004 (1989)]. If this change in
      neural synchronization is perceptually relevant for human listeners, then it may
      be predicted that changes in stimulus intensity and changes in the frequency
      difference between lower (F1) and higher (F2/F3) stimulus components should both
      affect perception of voicing. In a series of experiments, multiple continua of
      synthesized CVs varying in F1 cutback of the consonantal portion were played to
      listeners at levels ranging from 40 to 80 dB SPL. Across experiments, the
      frequency difference between F1 and F2 was manipulated by changing the onset
      frequency of F1 or F2. Subjects labeled more initial stops as voiceless as a
      function of increasing stimulus level and of decreasing frequency difference
      between F1 and F2. There was also an interaction between stimulus intensity and
      the frequency difference between F1 and F2 such that the effect of intensity was
      greater for smaller differences. These effects were reliable across a number of
      synthetic F1-cutback series, and the effect of intensity extended to a digitally
      edited series of hybrid CVs in which F1-cutback was varied by cross splicing
      naturally produced /da/ and /ta/. The effect of overall stimulus intensity was
      not affected by amplitude of prevocalic aspiration energy or by the presence or
      absence of release bursts. The results provide evidence for the perceptual
      significance of synchrony encoding of voicing for stop consonants.

PMID- 7714274
TI  - Use of temporal envelope cues in speech recognition by normal and hearing
      impaired listeners.
AB  - The temporal acuity of listeners with sensorineural hearing loss is currently a
      matter of some controversy. In this study, the ability of normal-hearing and
      hearing-impaired listeners to utilize temporal cues of speech was measured
      directly. In addition to natural (unprocessed) nonsense syllables, several
      processed-speech conditions were employed. Nonsense syllables were digitally
      processed to remove the original spectral information, resulting in a time
      varying speech envelope amplitude modulating a noise carrier. The processed
      speech conditions were the envelope of a broadband speech signal modulating a
      broadband noise, a low-pass speech signal modulating a low-pass noise, a high
      pass speech signal modulating a high-pass noise, and a two-channel signal
      comprised of the low- and high-pass modulated signals combined. Recognition of
      the envelope stimuli in quiet and also in modulated and steady noise backgrounds
      was tested. Listeners were tested at presentation levels yielding their maximum
      performance on a syllable recognition task. The hearing-impaired listeners
      performed more poorly on a recognition task than the normal-hearing listeners for
      unprocessed speech signals. However, for listeners with hearing losses of either
      flat or sloping configuration, there was no significant deficit in their ability
      to use temporal cues in speech, even in frequency regions of hearing loss up to
      70 dB HL. These results demonstrate that moderate to severe sensorineural hearing
      loss does not impair the temporal (nonspectral) acuity of listeners in terms of
      speech recognition, when audibility of the stimuli is compensated for.

PMID- 7714276
TI  - The health status and health care of ethno-cultural minorities in the United
      Kingdom: an agenda for action.

PMID- 7714275
TI  - Formant frequency values of vowels produced by preadolescent boys and girls.
AB  - The fundamental frequency (F0) and the first three formant frequency (F1, F2, and
      F3) values of vowels produced by 40 preadolescents were measured. There were five
      boys and five girls in each of four age groups: 5, 7, 9, and 11 years old. The 11
      nondiphthong vowels of Australian English which can be produced in a stressed
      syllable were used. The F0 values decreased with increases in age, but there was
      no difference between boys and girls. In general, the F1, F2, and F3 values
      decreased with increases in age, and the values for girls were higher than those
      for boys.

PMID- 7714277
TI  - Developing reflective practice in mental health nursing through critical incident
      analysis.
AB  - Critical incident analysis has been espoused as a valuable method of promoting
      reflective nursing practice and as a tool for developing curriculum content.
      Despite an obvious application to mental health nursing, however, there has been
      little detailed examination of the practicalities and educational value of
      critical incident analysis within a mental health nursing curriculum. This paper
      is based on the use of critical incident analysis within the mental health branch
      of a Project 2000 diploma course. It presents the content of material brought by
      students, teaching methods used to facilitate learning, and the progressive
      development of students' reflective processes over the course of a complete
      branch programme. Using Benner's (1984) From Novice to Expert, the authors
      explore questions regarding the nature and effects of the critical incident
      technique in attaining competence in mental health nursing skills. The authors
      conclude with a theory-based evaluation and analysis of this student-centered
      experiential approach to learning as a method for developing reflective practice,
      and suggest areas for educational research.

PMID- 7714278
TI  - Discontent without focus? An analysis of nurse management and activity on a
      psychiatric in-patient facility using a 'soft systems' approach.
AB  - Psychiatric nursing in the United Kingdom is undergoing major change as a
      consequence of the policy of community care. Whilst much has been written about
      the role of the community psychiatric nurse (CPN), less has been said about the
      preparedness of nurses in in-patient facilities to adapt to the changes.
      Checkland's (1981) 'soft systems' methodology was used to analyse the situational
      environment on an acute admission unit. It was found that an increased sense of
      accountability, combined with the demands of the Mental Health Act 1983, led the
      ward manager to develop a system, particularly in relation to discharge planning,
      in which his role was central. This left the ward staff feeling unrecognized and
      insufficiently experienced in a vital aspect of patient care. Lack of support
      from the college of nursing and inadequate staff development programmes were also
      found to have played a part in the situation. The use of reflection in action is
      recommended as a way of initiating changes in structure, processes and attitudes.
      Wider inferences are drawn concerning the competence of registered mental nurses
      (RMNs) practising in in-patient facilities, and the role of the colleges of
      nursing in operating effectively in the new care and market paradigms.

PMID- 7714279
TI  - A preliminary study of users' and nursing students' views of the role of the
      mental health nurse.
AB  - This paper is a preliminary study, part of a larger project which is endeavouring
      to ascertain the views of both users of mental health services and those of
      mental health branch students as to their perceived and desired role of the
      mental health nurse. Four groups of users (n = 28) and four groups of students (n
      = 44) were contacted, and recorded group discussions took place in gaining
      qualitative data that would feed into the main body of research. The views
      expressed by both users and students are interestingly convergent, but much
      concern was expressed as to the needed changes in the provision of the service
      and the danger for students on qualifying to become quickly incorporated into the
      prevailing dominant culture.

PMID- 7714281
TI  - The attitudes of British fundholding general practitioners to community
      psychiatric nursing services.
AB  - This study was designed to explore the attitudes of British fundholding general
      practitioners to community psychiatric nurses and the services they currently
      provide, and may provide in the future. The information was collected by postal
      questionnaire. Seventy-two fundholding general practitioners were identified
      within the East Sussex Family Health Authority, England; 20 (27%) completed and
      returned the questionnaire. The instrument was based on previously published
      work, with some adaptations relating to the fundholding element. The results
      confirmed previous research findings suggesting a favourable attitude towards
      community psychiatric nurses, and also identified the services they should
      provide. Three areas in need of urgent research were highlighted.

PMID- 7714280
TI  - Stress and coping strategies in community psychiatric nurses: a Q-methodological
      study.
AB  - With the development of the concept of community care there has been a
      significant expansion of the community psychiatric nurse (CPN) profession. The
      present study attempts to examine which aspects of their work CPNs currently find
      stressful. The study also examines the various strategies which CPNs feel to be
      useful in attempting to cope with such occupational stress. Forty-four CPNs in
      four health districts participated in this Q-methodological study which provided
      the opportunity for CPNs to construct their own concepts of stressors and coping
      strategies. The results obtained indicated that CPNs identified nine distinct
      areas of stress within their work, along with 12 distinct coping strategies which
      they considered useful in attempting to deal with such stress. The implications
      of these findings are discussed.

PMID- 7714282
TI  - Family burden in chronic mental illness: a review of research studies.
AB  - Early research has established that burden exists and has identified certain
      behaviours of mentally ill relatives that family members find most distressing.
      Further research has confirmed the accuracy of the early work and has focused on
      the severity of mental illness. Recent research has stressed the importance of
      social support in the study of caregiver burden. This paper explores the research
      literature that covers the concept of caregiver burden in the area of mental
      illness and also presents developed instruments for the study of caregiver
      burden.

PMID- 7714283
TI  - Developing a typology of family care: implications for nurses and other service
      providers.
AB  - The meanings attributed to the concept of care are considered. It is argued that
      whilst nursing has paid considerable attention to care in a professional
      (nursing) context, it has virtually ignored care as it is defined and construed
      by family carers. A new typology of family care is described which builds on the
      limited existing conceptual work in this area. It is further suggested that
      interventions which are intended to assist carers form a continuum ranging from
      services which are facilitative to those which are actually obstructive. In the
      light of these discussions, the implications of the new typology for nurses
      working with family carers are addressed briefly.

PMID- 7714284
TI  - Breast cancer patients' experiences of nursing care with the focus on emotional
      support: the implementation of a nursing intervention.
AB  - Nursing care with the focus on emotional support, aimed at improving breast
      cancer patients' adjustment to everyday life, was implemented. The women were
      offered the opportunity to talk about illness-related thoughts and reactions, as
      well as to express feelings of anxiety, fear and anguish with a nurse who
      listened, consoled and answered questions. The organizational changes included
      extensive co-operation between the surgical ward and primary health care, shorter
      waiting times, and changed routines around information about the diagnosis. A
      total of 26 Swedish women, aged 35-69, with newly diagnosed breast cancer,
      described their experiences of the disease and nursing care in a semi-structured
      interview 6 months after the primary treatment. Data were coded by open coding;
      themes and categories were formulated. Findings showed that emotional support, as
      well as organizational changes of care, led to feelings of safety and security.
      Most of the women could plan for the future despite a demanding situation. The
      study indicates that the nursing intervention may improve women's sense of
      control, and also that further changes in care are needed to meet their
      psychosocial needs, such as adequate information about medical treatment and more
      'confirming' relationships.

PMID- 7714285
TI  - A postal survey of continence advisers in England and Wales.
AB  - Improved continence services have been identified as a purchasing priority for
      1994-1995. A key figure in the continence team is the nurse continence adviser.
      However, although the Association for Continence Advice in the United Kingdom
      offers a set of guidelines for the role of continence adviser, the extent to
      which these were implemented across the country was unknown. In 1991, the
      Department of Health commissioned the Social Policy Research Unit of the
      University of York, England, to carry out a postal survey of all known continence
      advisers in England and Wales in order to provide basic quantitative information
      about the number of advisers in post, their professional qualifications, the
      structures in which they worked, and the nature of current practice. In this
      paper a brief resume of some of the main findings from the survey, which included
      both quantitative and qualitative data, is presented. The role of the continence
      adviser as a clinical nurse specialist and some of the implications for current
      practice are also discussed.

PMID- 7714286
TI  - Principle-based ethics and nurses' attitudes towards artificial feeding.
AB  - Nurses often institute artificial feeding for patients who would otherwise
      starve. Recently, the courts in the United States have favoured withholding or
      withdrawing feedings from patients who currently refuse or previously gave some
      indication they would refuse artificial nutrition and hydration. This paper
      investigates under what circumstances nurses feel justified in withholding
      artificial nutrition and hydration. Structured interviews were conducted with 40
      cancer care nurses from two sites, and 40 dementia care nurses from two sites.
      The interviews were based on two vignettes, one involving an alert patient with
      terminal cancer, the other a patient suffering end-stage Alzheimer's dementia,
      and were analysed for themes coinciding with principles of deontological ethics.
      Investigators found that autonomy, beneficence and non-maleficence most often
      guided nurses' decisions to withhold or implement artificial feeding.

PMID- 7714287
TI  - Munchausen syndrome by proxy in health care workers.
AB  - The literature on Munchausen Syndrome by Proxy (MSP) is reviewed to assess the
      extent of existing knowledge and the incidence of this syndrome among health care
      workers. Although use of this diagnosis appears to be increasing and broadening,
      it was not until the Beverly Allitt case in the United Kingdom in 1993 that this
      syndrome was used to explain the behaviour of a health care worker who harmed
      people in his/her care. However, a review of available details of previous health
      care workers accused of murder reveals that five shared some of the distinctive
      features of MSP. Although care must be taken when applying diagnoses, in view of
      the risk of morbidity and mortality which MSP poses for the people involved, it
      is important that health care workers become more informed and involved in
      understanding and detecting MSP.

PMID- 7714288
TI  - A comparison of substance use rates among female nurses, clerical workers and
      blue-collar workers.
AB  - The issue of impairment of practising professional nurses by alcohol and other
      drugs has become a critical concern since the 1980s. The literature abounds with
      conjectures about the large numbers of nurses who are impaired, often without
      valid data to support the claims that the problem in nursing is greater than it
      is in the general population. This study reflects an effort to compare the
      reported substance use of employed female nurses with that of two other groups of
      working females. Survey data from 920 nurses, 405 clerical workers and 200
      females employed in non-traditional trades jobs in two large eastern states in
      the US revealed that there was little evidence of 'abuse' of any of 15
      substances; nurses did not report higher rates of substance use than the other
      two groups; and most reported substance use occurred in the younger age groups,
      reflecting the national trend. The need for continuing research efforts and
      confirmation of valid data, and primary prevention efforts with young female
      workers, including at-risk student nurses, is made evident.

PMID- 7714289
TI  - Communication in nursing: the theory-practice relationship.
AB  - The theory-practice relationship and the use of communication and interpersonal
      skills in nursing have been recurrently identified as issues causing concern.
      Four research questions form the basis of this small-scale exploratory study
      investigating the views of nurse teachers, mentors and students into the theory
      practice relationship with regard to the communication and interpersonal skills
      theme of the Project 2000 common foundation programme (CFP) for British nursing
      students. Hierarchical focusing, involving individual interviews with teachers
      and mentors and small-group interviews with students, was undertaken. Volunteer
      sampling was used. Qualitative data analysis was undertaken using content
      analysis. Results are summarized with regard to each main research question.
      There was little consensus of opinion amongst participants, and the nature of the
      theory-practice relationship with regard to the communication and interpersonal
      skills theme for the CFP remains unclear. However, there was agreement that
      communication is fundamental to nursing and that the socialization process
      strongly influences the development of communication and interpersonal skills.
      There appears to be a reliance on mentors to assess student progress and
      determine whether they have knowledge underpinning practice. Classroom teaching
      was recognized as idealistic but the divisions in participants' opinions led to
      difficulty in determining whether a theory-practice gap actually exists. The main
      influences on the theory-practice relationship were the mentor's knowledge of the
      curriculum and mentoring system, the short amount of time spent in each placement
      and relationships between teachers, mentors and students. Recommendations include
      the need to ensure the reliability and validity of progressive assessment.

PMID- 7714290
TI  - A brief description of the methods of economic appraisal and the valuation of
      health states.
AB  - The interest of nurses in methods of economic evaluation appears limited to cost
      effectiveness analysis, with an apparent unawareness of other methods of economic
      appraisal and the types of efficiency they consider. The main methods of economic
      appraisal are discussed, and linked to different kinds of efficiency. Methods for
      the valuation of health states, an important accompaniment to the methods of
      economic appraisal, are briefly described along with some of the practical
      difficulties. If skilled nursing care--alone or with other disciplines--changes
      health status then the measurement and valuation of such states may be used to
      inform resource allocation decisions involving nursing. It could be argued that
      the main impact of nursing is on quality of life, and if so this suggests cost
      utility analysis, and not cost-effectiveness analysis, as the natural level of
      appraisal for nursing. The use of these methods in research, and participation in
      their future development, are both suggested as valid targets for nurses to aim
      for.

PMID- 7714291
TI  - Some reflections on the use of repertory grid technique in studies of nurses and
      social workers.
AB  - This paper discusses the repertory grid technique, from its development by George
      Kelly as a means of demonstrating cognitive/perceptual systems in individuals, as
      postulated in his Personal Construct Theory, to its use in studies in nursing and
      social work. The original concept having focused on the uniqueness of, and
      differences between, individuals' perceptions of the world, in recent years it
      has been applied to the examination of characteristics within groups. The
      theoretical basis for this is discussed, with reference to a selection of studies
      of nurses and social workers, including a small comparative study of psychiatric
      nurses, general nurses and social workers. The degree to which the findings of
      these studies may be generalized is discussed. In retrospect, some of the
      applications are considered to be outside the paradigm of the Personal Construct
      Theory which underlies the repertory grid technique.

PMID- 7714292
TI  - An interviewing style for nursing assessment.
AB  - The research literature on health care interviewing styles is reviewed. A
      critique of the traditional provider question-client answer style is offered, and
      an alternative style, the conversational interview, is advocated as more client
      focused and less interpersonally controlling. The potential of the conversational
      interview to produce an accurate shared understanding of the client's health
      status is discussed.

PMID- 7714293
TI  - Good nurse, bad nurse....
AB  - The construction of the nursing subject is discussed. The paper takes a
      historical perspective, arguing that the range of speaking positions available to
      the nurse is limited by gender, class and education. It evaluates the position of
      nursing in the university, showing how this also has propensity to limit the
      development of the nursing profession.

PMID- 7714295
TI  - A review of the health promotion and health beliefs of traditional and Project
      2000 student nurses.
AB  - In this study it was proposed that a more rigorous theoretical component in
      nursing education courses would produce a nurse who was a proficient health
      educator and promotor of health. A sound knowledge base will enable the student
      to develop positive attitudes and beliefs towards promoting health and providing
      health education as a part of nursing practice. To test this hypothesis, two
      groups of students were asked to complete a questionnaire and the answers
      subsequently compared. The results and data analysis supported the hypothesis
      only in a limited way and a further study on a larger group of students would
      provide greater insight into the question.

PMID- 7714294
TI  - A comparison of the stressors experienced by parents of intubated and non
      intubated children.
AB  - When children are ill enough to require admission to paediatric intensive care,
      parents may become distressed about their child's medical condition and this
      distress may be compounded by the unfamiliar nature of the highly technological
      environment. Parents of children who are sick enough to warrant intubation are
      particularly likely to be exposed to a frightening array of technological
      equipment. Seventy-one parents of intubated and non-intubated children completed
      the Parental Stressor Scale: Paediatric Intensive Care Unit (PSS:PICU). Overall
      the findings suggest that parents were most distressed (a) by the painful
      procedures to which their children were subjected, (b) by the sights and sounds
      of the intensive care unit and (c) by their children's reactions to intensive
      care. The behaviour of staff towards parents and the way that staff communicated
      with them caused the least distress. When the levels of stress reported by
      parents of intubated children were compared with those reported by parents of non
      intubated children, different patterns of stress were found. Painful procedures
      were a source of greater stress to parents of intubated children whereas the
      behaviour of staff and the children's reactions to the intensive care experience
      caused greater stress to the parents of the non-intubated children. In general
      the findings suggest that the needs of parents of non-intubated children are
      being overlooked, with staff focusing more of their attention on the parents of
      intubated children.

PMID- 7714297
TI  - Determinants of changes in nurses' behaviour after continuing education: a
      literature review.
AB  - Nursing continuing-education programmes may differ in the extent to which they
      affect nursing practice. Differences may be explained by characteristics of the
      participants' background, the programme itself, teacher(s), relationship between
      participants, relationship between participants and teacher(s), physical
      environment during the programme, participants' social system, knowledge, skills
      and attitudes, and intention to change. In this literature review, a model is
      presented which integrates these variables and which may be used to explain why
      continuing-education programmes have no, little or considerable effect. On the
      basis of current scientific knowledge, colleagues' and superiors' support emerges
      as the most important determinant of behavioural changes in nursing practice.

PMID- 7714296
TI  - The concept of cogitation.
AB  - The purpose of this paper is to define the concept of cogitation in order to
      promote theoretical clarity in research focusing on elderly nursing home
      patients. A concept analysis was undertaken, using the method described by
      Schwartz-Barcott & Kim (1986). After extensive dictionary searches, reviews of
      literature and a fieldwork phase, tentative criteria and a preliminary definition
      of the concept of cogitation were formulated, antecedents and consequences were
      defined, and demonstration cases presented.

PMID- 7714299
TI  - Preparing the practitioner for advanced academic study: the development of
      critical thinking.
AB  - Using an evaluative approach, this paper explores the concept of critical
      thinking and its development within a recently revised study skills programme,
      preparing practitioners for the academic post-registration courses in one college
      of health. The current and almost explosive move of nurse education in the United
      Kingdom into the halls of higher education seems to recognize the need for higher
      order thinking skills in preparation for the unpredictability of nursing
      practice. Using a quasi-experimental design, the qualitative data analysed from
      two groups of students who undertook the study skills programme were measured
      against a control group of students undertaking the same short professional
      development course through the more traditional university approach of 2 years
      part-time academic study. The findings acknowledge that the development of
      critical thinking needs time and exposure to others seeking similar goals. In
      addition, to encourage the process of critical thought, study skills applied to
      content should be offered, as well as attention to teaching/learning strategies.
      If higher education means a change in culture, of attitude towards learning, then
      a more comprehensive foundation programme may better commence this process. It is
      anticipated that through such a programme current practitioners may be enabled to
      achieve successfully within the new academic courses and ultimately be better
      equipped for the complex decision-making in practice.

PMID- 7714298
TI  - Assessing the quality of the working life of nurse educators in Finland:
      perceptions of nurse educators and their spouses.
AB  - As part of a broader descriptive study of nurse educators' well-being at work in
      Finland, the quality of working life was assessed by the nurse educators
      themselves and by their spouses (or another adult living with them). Data were
      analysed from 477 (68% of 706) educators from 25 institutes throughout Finland
      and from 409 (58% of 706) spouses. Nurse educators evaluated their working life
      as being good. Background factors that improved one or several features of
      working life were: young age, being married, permanent employment in a small
      institute in the countryside, and highschool education. Lack of freedom to choose
      the teaching field and tasks at work reduced the quality of working life. Nurse
      educators estimated that they did an average of 9.6 hours overtime a week;
      according to their spouses the figure was 12.7 hours. More than moderate amounts
      of negative stress, derived mainly from work, were reported. Interactions with
      people at work and the support obtained for their work were generally judged to
      be good. Participants reported that they were not very satisfied with
      relationships with college directors, while they were, generally, satisfied with
      relationships with students. The spouses estimated nurse educators' working life
      more negatively than did the educators themselves, with the exception of the
      balance between work and leisure time, which both groups estimated similarly.

PMID- 7714301
TI  - On being a 'stroke' patient.

PMID- 7714300
TI  - Portfolios: a developmental influence?
AB  - A situational analysis had demonstrated a need to help staff within an
      orthopaedic/trauma unit review past and plan future learning. One way of doing
      this is through the preparation of a portfolio. An action research project was
      undertaken to explore two research questions: Is the process of portfolio
      preparation in itself developmental? If so, what factors influence this
      developmental process? Development was seen as a process of change indicated
      through application of the characteristics of adult learners. The action involved
      meeting as a learning group to explore the process and discuss the problems.
      Questionnaires were completed by group members to raise issues for further
      discussion at interview. The interviews formed a summative evaluation of the
      process up to the last group meeting. Data were analysed through a process of
      thematic content analysis, resulting in the identification of various categories.
      These categories were then used to explore the two research questions. Findings
      suggest that the process itself does influence development by acting as an
      initiator to reflection on experience. Owing to the short time span and small
      numbers involved, the project was intended as an exploratory study and as such it
      has provided direction for future research.

PMID- 7714302
TI  - An apology.

PMID- 7714303
TI  - Moclobemide and nortriptyline in elderly depressed patients. A randomized,
      multicentre trial against placebo.
AB  - Moclobemide and nortriptyline were compared with placebo in a double-blind
      randomized multinational (Canada, Denmark and UK) trial comprising 109 patients
      of > 60 years of age with major depression (DSM-III-R). Patients were randomized
      to 7 weeks of treatment with doses of 400 mg/day moclobemide, 75 mg/day
      nortriptyline or placebo. It was necessary to adjust nortriptyline dosage in <
      20% of patients to maintain serum levels within the postulated therapeutic window
      of 50-170 ng/ml. At end of treatment, the remission rates were 23% for
      moclobemide, 33% for nortriptyline and 11% for placebo. Anticholinergic and
      orthostatic events occurred more often with patients on nortriptyline than either
      moclobemide or placebo.

PMID- 7714304
TI  - Clinical survey of a psychiatric mother and baby unit: characteristics of 100
      consecutive admissions.
AB  - Demographic, obstetric, clinical features and clinical outcome of 100 consecutive
      admissions to a psychiatric mother and baby unit are presented. Referral patterns
      by health services involved are also examined. 56% of admissions occurred within
      2 weeks of delivery and the mean duration of admission was 2 months. Patients
      were categorized as having schizophrenia (n = 20), affective psychosis (n = 56)
      or non-psychotic disorders (n = 24) and these three groups were compared. There
      were few demographic and obstetric differences between diagnostic categories. The
      affective psychosis group were more likely to have acute illnesses with an onset
      and admission occurring within 2 weeks of delivery. Women with non-psychotic
      disorders were also most likely to become ill within 2 weeks of delivery but
      tended to be admitted later. Only 7% of the affective psychotic and non-psychotic
      women were discharged separated from their infants. Women with schizophrenia were
      less likely to have acute admissions and required greater input of nursing and
      service resources than mothers with other illnesses but 50% were discharged
      without their infants. More research is needed into matching models of care to
      the needs of mothers with different kinds of chronic, recurrent and new episodes
      of mental illness that present after childbirth. There are few guidelines to aid
      clinical staff in assessing the risk, current or future, of significant harm to
      an infant as a consequence of maternal mental illness, particularly of
      schizophrenia.

PMID- 7714305
TI  - Functional impairment in depressed inpatients.
AB  - The Sickness Impact Profile (SIP) was administered to 95 patients with major
      depression. The SIP includes 12 subscales, each representing a specific area of
      sickness-related dysfunction. To relate these measures to psychiatric symptoms,
      patients also completed a measure of depression severity. Consistent with earlier
      findings, there were high levels of functional impairment. Impairment was
      correlated with symptoms but, as noted elsewhere, functional status does not
      always parallel symptom severity. The SIP, widely used with medical disorders
      but, to our knowledge, underutilized to assess psychiatric patients, may provide
      more precise assessment of the impact of psychiatric disorders on the
      individual's daily life.

PMID- 7714306
TI  - Phobic symptoms as predictors of nonresponse to drug therapy in panic disorder
      patients (a preliminary report).
AB  - Factors that predict nonresponse to drug therapy (brofaromine or fluvoxamine)
      were investigated in a sample of 44 panic disorder patients. We used a strict
      definition of nonresponse to find patients who did not respond at all after 12
      weeks of treatment. Using this definition, 15 patients (32.6%) were considered
      nonresponders. Nonresponders had a higher score on the Blood-Injury subscore of
      the Fear Questionnaire (FQ) and more often had high scores on several FQ
      subscores, indicative of comorbid phobic symptoms. These variables were
      subsequently used to predict nonresponse.

PMID- 7714307
TI  - Thyroid function in seasonal affective disorder.
AB  - Morning serum levels of triiodothyronine (T3), free thyroxine (F-T4) and thyroid
      stimulating hormone (TSH) were measured in Winter-Seasonal Affective Disorder
      patients in nondepressed state in summer and before and after light treatment in
      winter. Practically all patients had hormone levels well within the reference
      ranges. T3 and F-T4, but not TSH, were significantly higher in winter than in
      summer; this is considered a normal phenomenon. There was no significant
      correlation between hormone levels and severity of winter depression. Light
      treatment did not alter serum hormone levels.

PMID- 7714308
TI  - Correlates of premenstrual dysphoria in help-seeking women.
AB  - Comparisons were made between the premenstrual changes reported by nontreatment
      seekers (NTS) (n = 32) and those of treatment-seekers (TS) (n = 52). The
      Premenstrual Assessment Form Luteal Phase and Follicular Phase versions were
      completed and the Beck Depression Inventory, the Automatic Thoughts Questionnaire
      and the State-Trait Anxiety Inventory were completed at both the luteal and
      follicular phases. Prospective daily ratings were made for two treatment cycles
      on the Daily Ratings Form and TS were screened for a mood-disorder history. Using
      the commonly cited 30% decrease in dysphoric levels from the pre- to
      postmenstrual phases as the criterion of prospective confirmation, women with
      prospectively confirmed dysphoria (PMD +) were not significantly more symptomatic
      than those without prospective dysphoric confirmation (PMD -). However, TS were
      more symptomatic than NTS on measures of depression, anxiety and frequency of
      negative automatic thoughts but not on mood behaviour and physical changes
      reflected in the PAF scales. No demographic differences were found between TS and
      NTS. Results did not support the issue of requiring 'confirmation' of self
      reports within a help-seeking group or the use of the 30% criterion in
      particular. Findings further suggest that the 95-item PAF may be inadequate in
      differentiating TS from others.

PMID- 7714309
TI  - The efficacy of cognitive behaviour therapy in treating premenstrual dysphoric
      changes.
AB  - This study assesses the efficacy of cognitive behaviour therapy (CBT) in treating
      premenstrual dysphoric changes. The CBT condition (n = 24) aimed to modify
      dysfunctional thinking as a means of impacting on negative premenstrual symptoms
      and changes. The components of CBT were cognitive restructuring and assertion
      training. A comparison condition called 'information-focused therapy' (IFT) (n =
      9) aimed to present information only and did not address belief restructuring.
      The components were relaxation training, nutritional and vitamin guidelines,
      dietary and lifestyle recommendations, aspects of child management training and
      assertion training. Results indicated that the amelioration of anxiety,
      depression, negative thoughts and physical changes can be effectively addressed
      by either CBT or IFT. The extent to which a women's belief system is critical in
      the experience of premenstrual distress requires further empirical investigation.

PMID- 7714310
TI  - The effect of sodium fluorescein on argon green photocoagulation.
AB  - BACKGROUND: The absorptive and photosensitizing properties of sodium fluorescein
      (NaFl) injected prior to laser photocoagulation may affect the retinal laser burn
      threshold. METHODS: Photocoagulation was performed using an argon green laser
      with a Volk QuadrAspheric fundus lens in three anesthetized rabbits. Using a
      500um spot size and a 100msec duration, varying laser powers were delivered
      before and at various intervals after intravenous (i.v.) injection of NaFl.
      RESULTS: Photocoagulation effects were enhanced in all subjects after fluorescein
      injection with threshold reduced for up to 48 hours following injection.
      CONCLUSIONS: The effectiveness of photocoagulation following fluorescein
      angiography may be underestimated, although this may be clinically insignificant
      since most photocoagulation procedures are performed well above threshold.
      Nevertheless, these data should be considered in those situations where carefully
      controlled threshold burns are desired. In such circumstances, it is advisable to
      take additional care in selecting treatment powers if fluorescein has been
      injected or to delay photocoagulation for a minimum of 48 hours.

PMID- 7714311
TI  - Congenital hypertrophy of the retinal pigment epithelium serves as a clinical
      marker in a family with familial adenomatous polyposis.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) is characterized by the
      development of multiple adenomatous polyps of the large intestine and
      gastrointestinal tract. FAP leads to colon malignancy in 100 percent of untreated
      cases. Congenital hypertrophy of the retinal pigment epithelium (CHREPE) has been
      identified as a potential early clinical marker for FAP. METHODS: Two generations
      received ocular examinations. One subject demonstrated CHRPE and was already
      known to have inherited FAP. His son showed typical CHRPE lesions associated with
      FAP and has most likely inherited the FAP gene. RESULTS: This case report of a
      family with autosomal dominant familial adenomatous polyposis (FAP) demonstrates
      the role of CHRPE as a useful early detector of the inheritance of the FAP gene.
      CONCLUSIONS: Early intervention (ocular and colorectal examinations) and
      treatment (colectomy) is advocated to prevent malignancy.

PMID- 7714312
TI  - The role of carotid endarterectomy in the management of carotid artery disease
      and stroke.
AB  - BACKGROUND: Carotid endarterectomy to surgically clear the carotid artery
      bifurcation of atherosclerotic material was at one time one of the most common
      surgical procedures performed in this country. In recent years, however, there
      has been intense controversy over the appropriateness and efficacy of this
      procedure for the prevention of ischemic stroke. METHODS: This paper will first
      review the terminology and pathophysiology of cerebrovascular occlusive disease.
      The carotid endarterectomy procedure, as well as diagnostic techniques for the
      evaluation of carotid artery disease, will be described. Finally, the controversy
      surrounding the indications, benefits, and risks of carotid endarterectomy, the
      results of recent clinical trials and current recommendations for utilization
      will be discussed. RESULTS AND CONCLUSIONS: Initial results from multi-center
      clinical trials demonstrate that carotid endarterectomy can reduce the risk of
      subsequent stroke in patients with high grade (70-99 percent) stenosis who are
      symptomatic (i.e. who have had a documented ipsilateral transient ischemic attack
      or minor stroke). The complication rate of the surgeon, the patient's overall
      medical status, and the method of determining carotid stenosis should be factored
      into the decision to proceed. Surgical guidelines are less clear for patients
      with only moderate carotid stenosis or who are asymptomatic.

PMID- 7714313
TI  - Noninvasive assessment of the ocular circulation: color Doppler imaging.
AB  - BACKGROUND: Color Doppler Imaging (CDI) has become instrumental in the
      noninvasive study of vascular disorders. CDI provides information about presence
      and direction of blood flow, flow velocity and flow disturbances in real-time
      with anatomical localization. METHODS: The medical and ophthalmic literature was
      reviewed to gather information about color Doppler technology and its application
      in ocular disease. RESULTS: Resolution limits of conventional ultrasound have
      previously prevented reliable noninvasive imaging of small vessels in the eye.
      CDI now permits the reliable identification of small blood vessels and
      measurements of blood flow within the eye. CONCLUSIONS: Color Doppler technology
      remains prohibitively expensive and therefore is not widely available. How this
      technology can be used for ophthalmic application is still a relatively new area
      of research and more studies are needed to determine the reliability and
      limitations of CDI when it is used to image the eye and how it compares to other
      imaging techniques that are currently in use.

PMID- 7714314
TI  - A novel approach to providing educationally based low vision services and
      outreach clinical and vision support services to the visually impaired.
AB  - BACKGROUND: The Perkins Low Vision Service is affiliated with the New England Eye
      Institute, the primary teaching clinic of the New England College of Optometry.
      Low Vision Services for patients of all ages as well as vision services for the
      multi-impaired are provided on site at the Perkins School for the Blind in
      Watertown, Massachusetts. RESULTS: Evaluations are provided by the low vision
      team comprised of specialists with expertise in pediatric and rehabilitative
      optometry, special education, orientation and mobility training, rehabilitation
      teaching and the interns at the New England College of Optometry. The full scope
      of services offered as well as alternative modes of practice employed will be
      discussed.

PMID- 7714315
TI  - Yellow signal light timing and the dilemma zone.

PMID- 7714316
TI  - Musings of a Robert Wood Johnson health policy fellow.
AB  - BACKGROUND: Changes in national health policy affect all health care providers.
      To increase its understanding and involvement in health care development, in
      1973, the medical profession, through the Institute of Medicine, developed a
      formal program--the Robert Wood Johnson (RWJ) Health Policy Fellowships Program-
      in the nation's capital. METHODS: Each year, since the mid-'70s, the RWJ Health
      Policy Fellowships Program provides "hands-on" health policy development
      experiences, to mid-career health professionals. Participants obtain an
      understanding of the health policy process at the national level, and an
      opportunity to contribute to the formulation of new policies and programs.
      RESULTS: The author describes his 1989-1990 RWJ Fellowship year. He reports that
      health professionals can and do contribute significantly in the development of
      national health policy. He also observes that there has been minimal
      participation by optometrists in the RWJ Health Policy Fellowship Program. During
      his fellowship, the author observed that the optometry profession was poorly
      understood and underrepresented at the national level. CONCLUSIONS: There is a
      need for direct optometric involvement in national health policy development. The
      RWJ Health Policy Fellowships Program provides exemplary policy experiences. This
      and alternative methods to increase optometric involvement and participation in
      health policy development, are discussed.

PMID- 7714317
TI  - Do changes in pupil size and ambient illumination affect the duochrome test?
AB  - Vague and conflicting suggestions currently exist within the literature regarding
      the appropriate level of ambient illumination to use while conducting the
      clinical duochrome (bichrome) test. One proposal is that reduced illumination
      should be adopted since this allows the pupils to dilate, thereby increasing the
      chromatic interval and resultant test sensitivity. The aim of the present study
      was to determine whether changes in pupil size and ambient illumination do indeed
      alter the subjective duochrome response. Accordingly, eight young, visually
      normal subjects were dilated with 2.5 percent phenylephrine and tested while
      monocularly viewing the duochrome chart through 1, 3, 5 and 7mm artificial
      pupils. Additionally, the effects of performing the test through a 1.0 log unit
      neutral density filter and varying the overall room illumination were examined.
      There were no significant differences between the mean responses under all test
      conditions. The variability of individual responses decreased with increasing
      pupil size; however, a 4mm change in pupil diameter was required to alter the
      response variability significantly. Therefore it is recommended that the test be
      performed under the minimum practical ambient illumination conditions in order to
      minimize this variability.

PMID- 7714318
TI  - Optic disc drusen and associated venous stasis retinopathy.
AB  - METHODS: Optic disc drusen is not an uncommon diagnosis in clinical ophthalmic
      practice. Although associated complications are quite rare, they may be visually
      devastating. Complications include optic neuropathy and hemorrhagic retinopathy.
      A case report of extensive optic disc drusen with associated venous stasis
      retinopathy is presented. RESULTS: Long-term follow up showed increasing venous
      stasis retinopathy secondary to optic disc drusen. Cystoid macular edema formed
      that gradually decreased vision from 20/20 to 20/70. CONCLUSIONS: Although
      infrequent, complications of optic disc drusen can be visually devastating. There
      is no treatment for disc drusen, but some of the complications may be amenable to
      treatment.

PMID- 7714319
TI  - Visual characteristics of Missouri State Highway Patrol troopers.
AB  - BACKGROUND: The Missouri State Highway Patrol (MSHP) had 902 troopers on duty at
      the time of this study. The purpose of this study was to determine, for the first
      time, the visual characteristics of this group. METHODS: All 902 troopers were
      requested to be screened during early 1993 at their local MSHP troop
      headquarters. Vision screening was done by Department of Motor Vehicle Personnel
      using Keystone/Mast DVS II Driver Vision Screeners. The results, along with
      current prescriptions obtained from their eye care practitioners, were mailed to
      the author. RESULTS: A 94 percent response rate was achieved. The group's mean
      age was 38.7 years and most (98 percent) were male. Forty-seven percent wear an
      optical correction either some or all of the time and these were evenly divided
      between single vision and multifocal corrections. Seventy-four percent of eyes
      had uncorrected distance acuity of 20/20 increasing to 94 percent of eyes with
      20/20 when corrections were worn. CONCLUSIONS: The results of this study will be
      used as a basis to update MSHP vision standards for acquisition and retention of
      troopers.

PMID- 7714321
TI  - Respiratory-related discharge patterns of caudal raphe neurones projecting to the
      upper thoracic spinal cord in the rat.
AB  - Sympathetic activity is modulated by central respiratory drive. Bulbospinal
      neurones arising in the ventrolateral medulla and A5 region probably contribute
      to this modulation. In the present investigation the involvement of caudal raphe
      spinal neurones in relaying respiratory-related inputs to sympathetic
      preganglionic neurones was investigated. Experiments were carried out on
      anaesthetized, vagotomized, paralysed and artificially ventilated rats.
      Extracellular recordings were made from the cell bodies of 53 caudal raphe
      neurones activated antidromically by stimulating the spinal cord between T1 and
      T3. The axonal conduction velocities ranged from 0.7-9.1 m/s (median = 3.8 m/s).
      Thirty-six of 53 neurones (consisting of neurones with on-going activity and
      quiescent neurones activated with glutamate) were held long enough for detailed
      analysis. Of those recorded 26 were in the region of raphe obscurus, nine in
      raphe pallidus and one in raphe magnus. Twenty-five of 36 neurons had firing
      patterns related to phrenic nerve discharge. Of the four firing patterns defined:
      seven neurones had the highest probability of firing during inspiration
      (inspiratory-related), 10 neurones had the highest probability of firing during
      expiration (expiratory-related), 3 had the highest probability of firing during
      post-inspiration (post-inspiratory-related) and 5 had lowest levels of firing
      during early- and post-inspiratory phases (early and post-inspiratory depressed).
      Of 27 neurones with axonal projections through or to the region of the
      intermediolateral cell column in the upper thoracic cord 19 had a respiratory
      related discharge pattern. For respiratory-modulated neurones with on-going
      activity the median of the modal inter-spike intervals was 0.08 s. None of the
      neurones had an ECG-related firing pattern. The findings of this study also
      indicate a species difference between rats and cats regarding the physiological
      properties of some raphe-spinal neurones; i.e., an absence of ECG-related
      activity in the rats. The characteristics of the neurones recorded in this study
      are not those of 'typical' 5-HT-containing neurones with reference to axonal
      conduction velocities and discharge characteristics.

PMID- 7714320
TI  - Hemodynamic analysis of arterial pressure oscillations in conscious rats.
AB  - This study examined the contribution of rhythmic fluctuations of regional blood
      flow and vascular conductance to the genesis of low- (LF, 0.27-0.74 Hz) and high-
      (HF, 0.76-5 Hz) frequency oscillations of arterial pressure. In conscious 15-week
      old male intact (n = 11), guanethidine-sympathectomized (n = 8) and chronically
      sinoaortic denervated (n = 7) rats, arterial pressure and regional blood flow
      velocities (pulsed Doppler probes) were simultaneously recorded. Indices of
      subdiaphragmatic aortic, hindquarters and superior mesenteric conductances were
      calculated on a beat-to-beat basis over a 60-min period. Spectral power was
      calculated in the LF and HF bands using a fast Fourier transform algorithm.
      Transfer function analysis was also performed to calculate coherence and phase
      between arterial pressure and regional flows and conductances. In the LF band,
      spectral power of arterial pressure was decreased by approx. 85% in
      sympathectomized and approx. 54% in sinoaortic denervated rats. In the HF band,
      spectral power did not differ between the groups. In the three groups of rats,
      relations between arterial pressure and blood flow were characterized by a
      significant coherence in the HF band with little or no phase delay (synchronous
      oscillations). Relations between arterial pressure and vascular conductance were
      characterized in intact rats by a significant coherence in the LF band and a
      phase delay tending to pi radians (opposite oscillations), whereas in both
      sympathectomized and sinoaortic denervated rats, coherence did not reach
      significance. It is concluded that LF oscillations of arterial pressure are
      mostly secondary to rhythmic fluctuations in the vasomotor sympathetic tone in
      several regional circulations. Part of these oscillations originate from the
      synchronizing influence of the baroreceptor reflex. The study also suggests that
      the respiratory (HF) oscillations of arterial pressure involve fluctuations in
      cardiac output of purely mechanical origin.

PMID- 7714322
TI  - Gastrointestinal dysfunction in Parkinson's disease detected by
      electrogastroenterography.
AB  - Electrogastroenterography (EGEG) is a method to record electrical activities of
      the stomach and the intestine using skin electrodes. We investigated whether this
      method could be used to detect gastrointestinal dysfunction in patients with
      idiopathic Parkinson's disease. EGEG recordings were done with ten patients with
      idiopathic Parkinson's disease and ten control subjects before and after a meal.
      The patients showed changes in EGEG that were markedly similar to those of acute
      stage of vagotomized patients reported previously. Patients' increase rate in
      amplitude of gastric activity after the meal (median: 1.19) was significantly (P
      < 0.05, Mann-Whitney test) smaller than that of the controls (median: 2.84), and
      normal temporal frequency decrease of gastric activity after the meal was not
      seen in the patient group. These results suggest vagal nerve dysfunction of
      patients with Parkinson's disease, though other possibilities could not be
      denied. EGEG may be useful to assess patients' gastrointestinal dysfunction
      though we need further study to elucidate the relation between pathophysiology of
      their symptoms and EGEG findings.

PMID- 7714323
TI  - A subpopulation of large neurons of the sympathetic superior cervical ganglion
      innervates the NGF-rich submandibular salivary gland in young adult and aged
      mice.
AB  - One of the main target organs of the sympathetic superior cervical ganglion (SCG)
      is the submandibular salivary gland, which in male mice has a high concentration
      of endogenous NGF. To study the subpopulation of SCG neurons which innervate the
      submandibular glands in young adult and aged mice, a retrograde tracing with a
      fluorescent dye Fluoro-Gold (Fluorochrome, Englewood, CO, USA) was performed.
      Fluoro-Gold was introduced into the base of the submandibular salivary gland in
      anaesthetized animals. Four days later, both ipsilateral and contralateral SCG
      were studied. The results of the tracing were as follows: (a) in both young adult
      and aged mice about 45% of the sympathetic neurons of the SCG innervate the
      ipsilateral submandibular salivary gland; (b) the neurons innervating the
      submandibular gland form a subpopulation of large-sized neurons; (c) in young
      adult mice some 10% of SCG neurons innervate the contralateral SCG, while in aged
      mice only 1-2% have the same effect.

PMID- 7714324
TI  - GAP-43 and its relation to autonomic and sensory neurons in sciatic nerve and
      gastrocnemius muscle in the rat.
AB  - The presence of the growth-associated protein, GAP-43, in rat sciatic nerve and
      gastrocnemius muscle was studied, using indirect immunofluorescence, in lumbar
      sympathectomized and sham-sympathectomized rats. To study fast axonal transport
      and accumulation of immunogenic GAP-43, the sciatic nerves were crush operated, 6
      h before perfusion fixation. In sections of normal, crushed sciatic nerve GAP-43
      like immunoreactivity (LI) rapidly accumulated, on both sides of the crushes, in
      medium and thin sized axons. In double immunostaining experiments, GAP-43-LI was
      mainly colocalized with tyrosine hydroxylase (TH)-LI, or neuropeptide Y (NPY)-LI,
      markers of sympathetic nerves. In some axons, GAP-43-LI was colocalized with
      Substance P (SP)-LI. In perivascular nerve terminals in the gastrocnemic muscle,
      strong GAP-43-immunofluorescence was observed, in most cases colocalized with TH
      LI, but in some terminals with SP-LI. Three days after lumbar sympathectomy
      (removal of the L1-L4 sympathetic ganglia bilaterally), TH-LI and NPY-LI positive
      axons in the sciatic nerve were reduced in number by more than 90%. GAP-43-LI
      positive axons were reduced by about 50%. In the gastrocnemic muscle, some GAP-43
      LI positive terminals, but very few TH-LI positive nerve fibres, were found
      around blood vessels. No further changes were seen 8 days after sympathectomy. SP
      LI in axons in the sciatic nerve and in perivascular nerve terminals of the
      gastrocnemic muscle, did not change after sympathectomy; most of these axons also
      contained GAP-43-LI. S-100-LI was present periaxonally in the sciatic nerves, but
      it did not colocalize with GAP-43, indicating that Schwann cells contained no GAP
      43-LI in these experiments. The results show that, in normal adult rats, GAP-43
      LI is mainly present in sympathetic and sensory nerve fibers in sciatic nerve and
      in perivascular nerve terminals. The peptide is axonally transported, mainly in
      sensory and adrenergic axons.

PMID- 7714325
TI  - Histochemical, pharmacological, biochemical and chromatographic evidence that
      pituitary adenylyl cyclase activating peptide is involved in inhibitory
      neurotransmission in the taenia of the guinea-pig caecum.
AB  - The possibility that pituitary adenylyl cyclase-activating peptide (PACAP) is an
      inhibitory neurotransmitter has been investigated in the taenia of the guinea-pig
      caecum. The action of PACAP on muscle contractility and its ability to alter
      levels of adenosine-3':5'-cyclic monophosphate (cyclic AMP) and guanosine-3':5'
      cyclic monophosphate (cyclic GMP) were investigated. PACAP-1-27 was an effective
      agonist, giving relaxations comparable in magnitude to isoproterenol; its EC50
      was 3.4 x 10(-7) M. PACAP (10(-6) M) caused an almost two-fold increase in cyclic
      AMP levels; but the level of cyclic GMP was not affected. The relaxation caused
      by PACAP was slow in onset, with a latency of 5.8 +/- 0.8 s and reached a maximum
      at 9.1 +/- 1.1 s after onset. The relaxation was significantly reduced by apamin
      (10(-6) M) and suramin (10(-4) M) but was not reduced by tetrodotoxin (10(-7) M).
      Relaxation of the taenia coli caused by electrical stimulation of the inhibitory
      nerves was greatly reduced by apamin but only slightly reduced by suramin. PACAP
      like immunoreactivity (-IR) was localised immunohistochemically in varicose nerve
      fibres within the taenia coli and in the underlying myenteric plexus and circular
      muscle. Approx. 50% of vasoactive intestinal peptide (VIP)-IR nerve fibres in the
      taenia also had immunoreactivity for PACAP; conversely, almost all PACAP-IR
      fibres were immunoreactive for VIP. PACAP-IR and substance P (SP)-IR were
      generally in separate fibres; only about 5% of SP-IR fibres were PACAP-IR.
      Radioimmunoassay revealed tissue concentrations of PACAP-1-27 and PACAP-1-38 of
      1.0 +/- 0.1 and 2.1 +/- 0.3 (SEM) pmol/g wet weight of tissue, respectively.
      Material with PACAP-1-27 immunoreactivity co-eluted with authentic PACAP-1-27 on
      gel filtration chromatography, and PACAP-1-38 immunoreactivity also co-eluted
      with the authentic peptide. This study provides structural, chemical and
      pharmacological evidence that PACAP could be involved in inhibitory
      neurotransmission to the taenia coli of the guinea-pig caecum.

PMID- 7714326
TI  - Arterial baroreceptors are not essential for low frequency oscillation of
      arterial pressure.
AB  - Cardiovascular parameters exhibit spontaneous oscillations at the respiratory
      frequency, and in the low frequency range (LF < 0.20 Hz). Although LF is
      attributed to the sympathetic control, the mechanism responsible for the
      oscillation, whether instability of the baroreflex loop, or activity of a central
      nervous system pattern generator, is controversial. To answer this question, time
      series of arterial blood pressure, heart period and left external iliac blood
      flow from chloralose-anaesthetised dogs were examined by standard statistics as
      well as by autoregressive spectral and cross-spectral analysis. The circulation
      to the left hind-limb was isolated and connected to a constant-pressure perfusing
      system, to obtain mechanical uncoupling from the central circulation. Three
      steady-state conditions were studied. A device inserted into the common carotid
      arteries allowed the carotid sinus region to be in continuity with the animal's
      arterial system (CONTROL) or perfused at constant pressure by an external source
      (CAROTID BUFFER); bilateral cervical vagotomy was also performed (VAGI CUT).
      Intra-individual (beat-to-beat) variability of each parameter was evaluated by
      standard deviation (SD) of time series in the three conditions. The average SD of
      heart period was reduced in CAROTID BUFFER and in VAGI CUT; the SDs of arterial
      pressure and iliac flow were not changed by these interventions. Autospectra of
      iliac flow time series in CONTROL showed a prominent peak at 0.05 +/- 0.04 Hz
      (mean +/- SD of all experiments), accounting for 90 +/- 11% of the total
      variance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714327
TI  - A light-microscopic study of the intermediolateral nucleus following injection of
      CB-HRP and fluorogold into the superior cervical ganglion of the rat.
AB  - Sympathetic preganglionic neurons in the intermediolateral nucleus of the
      thoracic spinal cord of the adult rat which innervate the superior cervical
      ganglion (SPN-scg) were identified by means of retrograde transport of cholera
      subunit B-conjugated horseradish peroxidase and fluorogold. In horizontal
      sections of the spinal cord, the SPN-scg were observed to be arranged in clusters
      which displayed a characteristic triangular configuration. Within this triangle,
      the cells showed no preferential orientation for their long axes were oriented
      obliquely, transversely or longitudinally. The dendrites arising from these
      clusters were oriented either longitudinally, medially, or laterally. The
      medially-oriented dendrites formed a subependymal plexus and some have been
      observed to cross the midline to the opposite side. The most significant finding
      was the presence of the white matter dendritic plexus which was formed by the
      laterally-directed bundles of dendrites. The present findings thus suggested that
      SPN-scg may be regulated by means of two circuits: the classical (medial) core
      circuit and a paralateral circuit which may convey supraspinal afferent inputs to
      the SPN-scg.

PMID- 7714328
TI  - Changes in cerebral blood flow estimated after stellate ganglion block by single
      photon emission computed tomography.
AB  - The validity of the hypothesis that the cerebral vasculature is under the control
      of sympathetic innervation was investigated using brain scintigraphy imaging
      before and after stellate ganglion block (SGB). The experiment with HM-PAO showed
      a definite increase in the blood flow of the brain on the block side on both by
      the dynamic images and the SPECT images. The tympanic temperature (Tty) of the
      block side decreased significantly after SGB, compared to the unblock side in
      this study, as had been reported before. This change in Tty coinsided with the
      increase in cerebral blood flow as mentioned above. This study demonstrated that
      the cerebral vasculature is under the control of sympathetic innervation, the
      pathway of which is relayed and/or passes through the stellate ganglion. We
      conclude that SGB increases intracerebral blood flow and can also exert secondary
      effects systemically due to CNS blood flow changes as have been previously
      reported.

PMID- 7714329
TI  - Modulation of the cardiovascular defence response by low frequency stimulation of
      a deep somatic nerve in rats.
AB  - In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the
      dorsal part of the periaqueductal grey matter (PAG) produced a pressor response
      with tachycardia and vasodilatation in the hind limb, a pattern known as the
      'cardiovascular defence reaction' owing to its resemblance to fear-induced
      hemodynamic changes. Following a 20-min period of stimulation of the peroneal
      nerve at 10 Hz with current intensities sufficient to recruit group II and III
      fibres the pressor component of the response was significantly reduced compared
      to control rats. The maximum decrease of the PAG-evoked pressor response was
      about 50% (from 32.0 +/- 0.7 to 16.6 +/- 5.9 mmHg). The effect lasted for between
      60 and 290 min and was not correlated to baseline blood pressure changes observed
      after the stimulation of the nerve. In contrast, the tachycardia and hind limb
      vasodilator components of the defence response as well as their baseline values
      remained unchanged. Resting blood pressure did not change significantly in
      control rats but showed a small progressive increase in stimulated rats which
      reached significance 90-100 min after the stimulation. These results suggest that
      the afferent input from high threshold fibres in a muscle nerve can produce a
      selective and long-lasting depression of the vasoconstrictor components of the
      midbrain-evoked cardiovascular defence response. This effect is discussed in
      relation to the long-lasting sympathoinhibitory effects of acupuncture-like
      stimulation or sustained physical exercise.

PMID- 7714330
TI  - Purification and measurement of secretory IgA in mouse milk.
AB  - An important factor limiting better understanding of the protective role of sIgA
      at mucosal surfaces is the limited availability of the purified immunoglobulin.
      Among other things, purified sIgA is needed for use as a standard in measurements
      of the concentration of this immunoglobulin in mucosal secretions, particularly
      in mice, where several models of mucosal infections are available. We describe
      here a simple method by which one can obtain a mean of 3.5 ml of milk per mouse
      without a breast pump. Immunoblotting studies after native PAGE demonstrated that
      the milk contained mainly 420 kDa dimeric sIgA and higher polymeric forms of
      sIgA; only a trace of monomeric IgA was present. Similar immunoblotting studies
      after SDS-PAGE revealed that a portion of the sIgA was dissociated by this
      treatment. The 420 kDa sIgA was purified by salt fractionation, gel filtration,
      and affinity chromatography, and the purity of the final product was demonstrated
      by immunoblot analysis of biotinylated polypeptides after reduction of
      biotinylated protein. The concentration of 420 kDa sIgA in whey was measured by
      densitometry of immunoblot bands, using the purified 420 kDa sIgA as a standard,
      and found to be 1.0 +/- 0.3 mg/ml.

PMID- 7714331
TI  - Lipopolysaccharide in concentrations above 40 ng/ml stimulates proliferation of
      the IL-6-dependent B9 cell line.
AB  - The B9 assay is known to be a specific and sensitive assay for the estimation of
      interleukin-6 activity. This assay was found to be compromised by
      lipopolysaccharide in concentrations > or = 40 ng lipopolysaccharide per ml. The
      lipopolysaccharide stimulates proliferation of the B9 cell line in a dose
      dependent manner both when measuring the proliferation by thymidine incorporation
      and when using the MTT assay. However the LPS dose-response curve is different
      compared to the dose-response curve for IL-6. A sample containing 100 ng LPS/ml
      but no IL-6 would be estimated erroneously to contain 12 pg IL-6. The
      interference of lipopolysaccharide is totally abolished by the addition of
      polymyxin B to the samples but the addition has no effect on the IL-6 induced
      proliferation.

PMID- 7714333
TI  - Immunological detection of Clostridium botulinum toxin type A in therapeutic
      preparations.
AB  - The potent neurotoxins produced by strains of Clostridium botulinum act by
      blocking the release of acetylcholine from peripheral nerve junctions. This
      specific action of the botulinum neurotoxins is now being exploited
      therapeutically to treat a variety of conditions involving involuntary muscle
      spasms. We aimed to develop a sensitive and specific enzyme-linked immunosorbent
      assay (ELISA) which may be used in parallel with the currently accepted mouse
      bioassay test for the determination of botulinum neurotoxin type A in therapeutic
      preparations. High titre polyclonal antitoxins and their biotin derivatives,
      highly labelled horseradish peroxidase (HRP)-antibody conjugates, and
      streptavidin-biotin-HRP complexes were prepared and used in a sandwich ELISA for
      the detection of pure neurotoxin and neurotoxin in therapeutic material. The
      ELISA utilized either a monoclonal or polyclonal antibody as capture agent and
      HRP-labelled IgG or F(ab')2 fragment as second antibody. The limit of detection
      was 4-8 pg of purified toxin/ml (gcv < 13%), equivalent to 1-2 mouse bioassay
      units/ml. The assay was used to evaluate therapeutic preparations and the results
      compared with the mouse bioassay. The lower limit of detection for a therapeutic
      preparation of BoTxA was 2-5 mouse bioassay units/ml. Although across different
      manufacturers and bulk products there was no correlation between immunologically
      detected neurotoxin and its biological activity in different therapeutic
      preparations (r = -0.44, p = 0.34, n = 8), the assay could be used to quantify
      neurotoxin in therapeutic preparations derived from the same bulk concentrate and
      manufacturer. The assay is relatively simple, and may be readily adapted to
      routine monitoring of BoTxA content in therapeutic preparations.

PMID- 7714332
TI  - Selective binding of peripheral blood lymphocytes to the walls of cerebral
      vessels in frozen sections of human brain.
AB  - In order to identify the factors that control the binding of blood leucocytes to
      cerebral blood vessels we have modified and applied the frozen section assay of
      Stamper and Woodruff to the study of human brain. Cryostat sections of brain
      tissue obtained at post mortem were overlaid with blood lymphocytes and
      experimental conditions were defined which permitted optimum binding of the cells
      to transected blood vessel walls. The maximal binding of lymphocytes to cerebral
      vessels occurred when 6 x 10(6) lymphocytes were overlaid onto brain sections for
      30 min at 7 degrees C with gentle agitation. Only a small proportion (0.01%) of
      the added lymphocytes bound to exposed cerebral vessels. However, lymphocytes
      were far more adherent than monocytes and polymorphonuclear cells (7-fold and 11
      fold respectively: p < 0.001) and activation of lymphocytes with IL-2 enhanced
      their binding to blood vessel walls (mean 130% increase; p < 0.03). Further
      analysis revealed that CD4-positive T lymphocytes were the predominant cell
      population binding to the blood vessels. Antibody blocking studies showed that
      lymphocyte binding to cerebral blood vessels was inhibited by pretreating the
      lymphocytes with anti-CD11a, anti-CD18 or anti-CD49d (p < or = 0.02) and
      immunohistochemical studies revealed the presence of the counter-receptors ICAM-1
      (CD54) and VCAM-1 (CD106) for these adhesion molecules in addition to the
      presence of E-selectin (CD62E) and P-selectin (CD62P) on the cerebral blood
      vessels. The establishment of a technique in situ which measures selective
      binding of CD4-positive peripheral lymphocytes to sections of cerebral blood
      vessels will assist in the molecular characterization of factors that control the
      interaction of leucocytes with the blood-brain barrier in health and disease.

PMID- 7714334
TI  - Cytokine-stimulated chemotaxis of human neutrophils in a 3-D conjoined fibrin gel
      assay.
AB  - The ability of neutrophils to migrate through three-dimensional (3-D) tissues in
      response to chemical stimuli is critical to their host defense function. However,
      studies characterizing stimulated migration in vitro have been largely limited to
      two-dimensional (2-D) surfaces. In this study, we have employed direct
      observation methods to quantify human neutrophil migration in 3-D fibrin gel
      using time-lapse video microscopy and automated cell tracking methods. A novel 3
      D conjoined gel assay was developed to establish experimentally quantifiable and
      theoretically predictable diffusion gradients of chemotactic factors. This assay
      was used to measure objective migration parameters, namely the random motility
      and chemotaxis coefficients, in response to the cytokine, interleukin-8 (IL-8).
      The random motility coefficient, mu, showed a biphasic dependence on IL-8
      concentration with a maximum of 1.1 x 10(-8) cm2/s at 5 x 10(-8) M IL-8; no
      significant motility was observed in the absence of IL-8. We further established
      the dependence of cell orientation bias, phi, on the concentration and gradient
      steepness (i.e., specific gradient, SG) of IL-8. Results indicate that phi
      increases with increasing SG, provided the concentration is maintained
      sufficiently low, which we conjecture to result from minimizing IL-8 receptor
      down-regulation. The chemotaxis coefficient, chi, was maximum at an intermediate
      SG for both IL-8 concentrations studied. We also examined the applicability of
      this assay to estimate mu and chi from indirect measurements of chemotaxis,
      namely the simpler measurement of cell redistribution after a prescribed
      incubation time, as opposed to direct cell tracking measurements. By virtue of
      measuring chi, this is the first quantitatively objective study of mammalian cell
      chemotaxis in a physiologically relevant 3-D gel and, in particular, of
      neutrophil chemotaxis on any substratum in response to the physiologically
      relevant chemotactic factor, IL-8.

PMID- 7714335
TI  - Quantitative dot-blot assay for low titer anti-lipopolysaccharide antibodies in
      human plasma.
AB  - Low titer antibodies in plasma are very hard to detect by enzyme-linked
      immunosorbent assay (ELISA) mainly because of high nonspecific binding of various
      plasma proteins to the plastic substratum. In this report we present a sensitive
      and quantitative dot-blot assay which overcomes the high nonspecific binding
      problem and enables the detection of very low antibody titers in plasma. Natural
      low titer antibodies to Gram negative bacteria's lipopolysaccharide in plasma of
      healthy donors could not be detected by ELISA. However, by using nitrocellulose
      membrane as the carrier for the antigen and enhanced chemiluminescence as the
      detection method, we could detect and quantify low titers of anti
      lipopolysaccharide antibodies even in undiluted plasma with no background
      interference. The dot-blot assay is linear, in semilogarithmic plot, over a broad
      range of plasma dilutions. This assay will enable the early detection of antigen
      specific antibodies in immune processes such as in infectious diseases and
      vaccination.

PMID- 7714337
TI  - An improved method for purifying human thymic dendritic cells.
AB  - Thymic dendritic cells (DC) play a prominent role in the immune response as they
      constitute a key element involved in the maturation of thymocytes in the thymus.
      Human thymic DC, like DC from other lymphoid organs, represent a minor cell
      population (< 2%) of the thymus. Since these cells cannot replicate in vitro, the
      development of efficient purification methods is an essential prerequisite for
      extensive functional studies. DC express high levels of HLA-DR, a cell surface
      marker of the MHC class II antigen which is not exclusive to DC. Since no
      specific human thymic DC marker has been identified so far, DC purification
      methods are mainly based on depletion of particular subgroups of cells. We report
      here an improved method for purifying human thymic dendritic cells. In contrast
      to prior work, CD2+ thymocytes were first depleted by rosetting with
      neuraminidase treated sheep red blood cells. The nonrosetted cells were separated
      in a Percoll gradient, and the low-density cells were subsequently depleted of
      nondendritic cells by using thymocyte and macrophage specific monoclonal
      antibodies and either magnetic bead depletion or cytofluorometry. Cell
      populations (18-55 x 10(6) cells) obtained following magnetic bead purification
      were at least 80% HLA-DR+/CD2- and exhibited ultrastructural morphological
      features and functional activities such as those described previously for thymic
      DC. This improved method was compared with different purification approaches that
      use various combinations of cell density-based separation techniques and cell
      surface specific markers antibody reactivity. The magnetic beads depletion
      approach provided higher yields.

PMID- 7714336
TI  - Application of a dual color detection scheme in the screening of a random
      combinatorial peptide library.
AB  - Selectide Technology is a random synthetic combinatorial library method in which
      millions of random compounds are screened in parallel for their ability to bind
      to a tagged macromolecular target. The library consists of millions of beads and
      each individual bead expresses a unique chemical compound such as a peptide. In
      the standard enzyme-linked colorimetric detection scheme, the positive bead which
      turns color is isolated for microsequencing. In this paper, a dual color
      detection scheme using two sequential orthogonal probes is described. This dual
      color system enables one to rapidly differentiate false positive beads from true
      positive beads, resulting in a much more efficient use of the microsequencer.

PMID- 7714338
TI  - Stabilization and surface modification of monoclonal antibodies by 'bi-layer
      encagement'.
AB  - A two step simple procedure for antibody stabilization in soluble form was
      developed. The antibody is first treated with low molecular weight polyaldehyde
      (polyglutaraldehyde). Following removal of non-bound polyaldehyde the antibody
      polyaldehyde conjugate is crosslinked by polyamine (alkyl amine derivative of
      polyglutaraldehyde). Feasibility studies were successfully conducted employing
      monoclonal antibody raised against horseradish peroxidase as model system. The
      stabilized antibody preparation exhibited improved thermal stability, enhanced
      resistance to proteolytic digestion and higher 'specific binding activity' in
      ELISA test, without losing its capability to bind large antigen (enzyme) or being
      recognized by another antibody (goat anti-mouse IgG).

PMID- 7714339
TI  - Quantification of des-Arg9-bradykinin using a chemiluminescence enzyme
      immunoassay: application to its kinetic profile during plasma activation.
AB  - There is a renewed interest in the kininase I pathway of kinin metabolism,
      because des-Arg9-bradykinin (des-Arg9-BK) and des-Arg10-Lys-BK are selective and
      potent agonists of the B1 receptors, that are apparently upregulated by tissue
      injury. We have developed a polyclonal rabbit antiserum against des-Arg10-Lys-BK.
      In a radioimmunoassay for des-Arg10-Lys-BK, this antiserum exhibited high
      specificity. Notably, native kinins with the C-terminal Arg residue, bradykinin
      (BK) and Lys-BK, did not cross-react to a significant extent, whereas des-Arg9-BK
      and digoxigenin (DIG)-des-Arg9-BK exhibited a complete cross-reactivity. The
      antibodies were used to set up a sensitive chemiluminescence enzyme immunoassay
      (CLEIA) using the DIG-anti-DIG system as intermediate for the revelation of the
      immune complexes. The detection limit and the half-maximal saturation
      concentration for des-Arg9-BK were 27 and 1530 fmol/ml respectively. This assay,
      as well as another for BK quantification, have been applied in vitro to rabbit
      plasma activated by kaolin. The conversion of BK into des-Arg9-BK was generally
      efficient, and the persistence and concentration of both peptides were increased
      in the presence of enalaprilat an inhibitor of the angiotensin converting enzyme
      (ACEI). Rabbits treated with bacterial lipopolysaccharide exhibited an increase
      of plasma immunoreactive des-Arg9-BK that was potentiated in animals also treated
      with ACEI. This CLEIA for des-Arg9-BK is a new analytical tool applicable to
      analyze of the kininase I metabolites of kinins in vitro and in vivo.
      Measurements of des-Arg9-BK may be useful indicators of the kallikrein-kinin
      system activation.

PMID- 7714340
TI  - Quantitation of IL-1 beta mRNA by a combined method of RT-PCR and an ELISA based
      on ion-sensitive field effect transistor.
AB  - A method for quantitative RT-PCR using ELISA detection was developed and applied
      to the quantitation of IL-1 beta mRNA in clinical samples. To compensate for the
      'tube effect' of RT-PCR, a synthetic RNA, pRSET RNA, was added to sample
      solutions as an internal standard and co-amplified with IL-1 beta mRNA. Sense
      primers for IL-1 beta and pRSET were labeled with digoxigenin and FITC,
      respectively, while anti-sense primers for both were labeled with biotin. Double
      stranded PCR products were captured by two solid-phase pipettetips. One was
      coated with an anti-digoxigenin antibody and another with an anti-FITC antibody,
      and sandwiched by avidin-urease, and their activities were measured by coupling
      them with a pH-FET in a pH-measuring cell containing urea solution. The ratio of
      the signal intensity for IL-1 beta to that for pRSET was used to quantify the
      concentration of IL-1 beta mRNA. A calibration curve was obtained by using a
      known amount of AW 109 RNA as an external standard of IL-1 beta RNA. It was found
      that 10(2)-10(6) copies of IL-1 beta mRNA were measurable by the present method.
      Expression levels of IL-1 beta mRNA in clinical samples, such as monocytes of
      peripheral blood or synovial cells from patients with RA or OA, were determined.

PMID- 7714341
TI  - Specific and sensitive quantitation of transforming growth factor beta 3 by
      sandwich enzyme-linked immunosorbent assay.
AB  - Transforming growth factors beta (TGF-beta) consist of a highly homologous family
      of 25 kDa dimers involved in a diverse array of biological functions. Progress in
      understanding the biology of the third isoform (TGF-beta 3) of this family has
      been limited by the absence of a quantitative assay for TGF-beta 3. Here we
      report the development of a sensitive and specific sandwich enzyme-linked
      immunosorbent assay (SELISA), which is based on an anti-TGF-beta mouse monoclonal
      IgG as the capture antibody and chicken anti-recombinant-hTGF-beta 3 IgY as the
      secondary antibody. This assay can quantitate TGF-beta 3 in complex biological
      fluids, with a detection limit of 2 pg and no cross-reactivity or interference
      with as high as 1000-fold molar excesses of either TGF-beta s 1, 2 or 1.2. This
      TGF-beta 3 SELISA is the first reported assay for the direct and sensitive
      quantitation of TGF-beta 3 in complex biological fluids.

PMID- 7714343
TI  - Beta-endorphin and "overt" pain measures in children.

PMID- 7714342
TI  - Cassette vectors directing expression of T cell receptor genes in transgenic
      mice.
AB  - We describe a pair of cassette vectors that can be used to express rearranged T
      cell receptor genes in transgenic mice. Short DNA fragments containing rearranged
      V alpha and V beta segments are readily amplified from T cells and introduced
      between artificial cloning sites. Transgene-derived mRNAs are transcribed under
      the control of the natural TCR alpha and -beta promoter/enhancer elements. Using
      this vector, we have obtained transgenic mouse lines which display transgene
      encoded TCR alpha and beta chains on a majority of T cells.

PMID- 7714344
TI  - The prevalence of phantom sensation and pain in pediatric amputees.
AB  - Phantom sensations and pain occur with an unknown frequency in children. We
      hypothesized that such experiences are common among children, and occur more
      often than is recognized by health-care personnel. Children and adolescents, ages
      5-19 years, who had undergone limb amputation in the past 10 years, served as
      subjects for this retrospective study. Subjects were divided into three major
      groups depending upon the indication for amputation: congenital deformity (CD),
      trauma/infection (TI), and cancer (Ca). Surveys assessing phantom sensations and
      phantom pain were mailed to children and their parents/guardians. The incidence
      of phantom sensations was 100% in each group, and phantom pain occurred in the
      overwhelming majority. Both types of phantom phenomena began within days of
      surgery for almost all patients. Seventy-five percent of children and adolescents
      who had experienced phantom pain also had preoperative limb pain. At the time of
      the study, phantom pain had resolved in only 35% of the subjects. Phantom pain
      was documented in the medical records of only 40% of those answering positively
      to questions regarding phantom pain on the questionnaire. We conclude that
      phantom pain occurs commonly in children and adolescents. The association of
      preoperative pain in the diseased extremity and the later occurrence of phantom
      pain suggests that preoperative regional anesthesia may prevent phantom pain.

PMID- 7714345
TI  - Spread of thoracic epidural analgesia during upper abdominal surgery.

PMID- 7714346
TI  - A critique of instruments and methods to detect, diagnose, and rate delirium.
AB  - This document reviews existing instruments for evaluation of delirium.
      Instruments have been grouped into four categories: tests that screen for
      cognitive impairment, delirium diagnostic instruments, delirium-specific
      numerical rating scales, and laboratory and paraclinical exams. Analysis of
      instruments was based on comparison of their psychometric properties as well as
      subjective judgment. Guidelines are suggested for choosing the appropriate
      instrument according to the type of clinical evaluation or delirium research
      envisaged. Important factors in choosing an instrument, besides the
      appropriateness of its psychometric characteristics, include administration time
      constraints, level of rater expertise, and patient capabilities. By familiarizing
      investigators with the variety of evaluation instruments available, this work
      should permit more appropriate instrument selection in future studies on
      delirium.

PMID- 7714347
TI  - Withdrawal with transdermal fentanyl.

PMID- 7714349
TI  - Classification of macular leprosy lesions--limitation of histological
      correlation.

PMID- 7714348
TI  - Efficacy and pharmacokinetics of a new controlled-release morphine sulfate 200-mg
      tablet.
AB  - Nineteen of 25 patients (14 female) with advanced malignant disease completed a
      randomized controlled trial of a new high-dose (200 mg) tablet formulation of
      controlled-release morphine. Compared with the currently available 100-mg tablets
      there were no differences in pain severity or adverse effects with the new
      formulation. In four patients, full 12-hr plasma morphine concentration profiles
      at steady state were obtained and showed no significant differences between the
      same dose provided as 100-mg and 200-mg tablets in Cmax, tmax, or other
      pharmacokinetic indices.

PMID- 7714350
TI  - Audiovestibular system, fifth and seventh cranial nerve involvement in leprosy.
AB  - Thirty-nine patients with leprosy and fifteen sex- and age-matched controls were
      investigated for disorders of the fifth and seventh cranial nerves and that of
      the audiovestibular system. Sensorineural hearing loss found to be of cochlear
      origin was detected in eight (22%) of the patients with leprosy compared to none
      in the control group (p > 0.05). Vestibular dysfunction was noted in four
      patients (11.1%) compared to none in the control group (p < or = 0.05). Two cases
      were found to have fifth nerve involvement and one (2.8%) had seventh nerve
      involvement. None in the control group had fifth or seventh nerve deficit.

PMID- 7714352
TI  - A clinico-pathological study of macular lesions in leprosy.
AB  - One hundred twenty histologically confirmed cases of leprosy having macular
      lesions were evaluated clinically and histopathologically according to Ridley
      Jopling classification. Of these 120 cases, the majority (91 or 75.8%) were young
      adults. The main clinical findings were: a single macule in 42 patients (35%),
      multiple macules 2-5 in numbers in 35 patients (29.1%), 6-10 macules in 17
      patients (14.1%) and more than 10 macules in 26 patients (21.6%). Impairment of
      sensation over the macular lesions was present in 62 cases (51.6%), total loss of
      sensation was noticed in 31 patients (25.8%) and sensation was intact in 27
      patients (22.5%). Acid-fast bacilli were detected in 11 cases (9.1%) by slit-skin
      smear examination. Clinical examination of the 120 cases revealed features of TT
      in 16 (13.3%), BT in 41 (34.1%), BB in 11 (9.1%), BL in 13 (10.8%), LL in 7
      (5.8%) and indeterminate leprosy (IL) in 32 patients (26.6%). On the contrary,
      histologically there were 22 cases of TT (18.3%), 38 cases of BT (31.6%), 8
      (6.5%) BB, 10 BL (8.3%), 7 LL (5.8%) and 35 cases of IL (29.1%).
      Histopathological features were consistent with the clinical picture in 84
      patients (70%).

PMID- 7714353
TI  - Pefloxacin in leprosy.
AB  - Fluoroquinolones, a new class of compounds characterised by broad antimicrobial
      spectrum including mycobacteria together with limited toxicity, have recently
      been introduced in the chemotherapy of various human infectious diseases.
      Pefloxacin, one of the members of this class, was recently demonstrated to be
      bactericidal against M.leprae in the mouse foot-pad model and clinically
      beneficial in lepromatous leprosy patients. Clinical response to standard MDT
      with added pefloxacin in ten previously untreated (both PB and MB) was compared
      with that in ten similar patients on MDT alone in the present trial. The results
      of chemotherapy were quantified by a method of clinical scoring. This pilot study
      showed that addition of pefloxacin led to significant and rapid clinical
      improvement. There were no side effects attributable to pefloxacin.

PMID- 7714351
TI  - HIV infection amongst leprosy patients in south India.
AB  - In a pilot study, 463 leprosy patients (374 males and 89 females) were
      investigated for HIV-1 and HIV-2 antibodies by screening tests. Sera positive by
      the screening tests were subjected to confirmatory tests. Three cases were
      confirmed to be positive for HIV, two for HIV-1 and one for HIV-2. All the three
      positive cases were young males, who had visited commercial sex workers. No
      correlation was found between the type of leprosy and HIV infection. This is the
      first report of HIV infection amongst leprosy patients from South India.

PMID- 7714354
TI  - Deformity incidence in leprosy patients treated with multidrug therapy.
AB  - The records of 2,285 (2,007 paucibacillary (PB) and 278 multibacillary (MB))
      cases of leprosy which were declared as released from treatment (RFT) after
      multidrug therapy (MDT) and under surveillance as per the National Leprosy
      Eradication Programme (NLEP) guidelines in the rural field practice area of
      Central Leprosy Teaching & Research Institute (CLTRI), Chengalpattu, between
      September 1986 and September 1993 were analyzed for collecting data on the
      incidence of deformity. Of the 2,285 cases 2,053 (1,947 PB and 106 MB) did not
      have deformity at the commencement of treatment. Three MB cases and one PB case
      out of the 2,053 developed deformity (all grade II) during the course of
      treatment. No patient developed deformity during surveillance. Thus the deformity
      incidence in the population of patients was 0.681 per 1000 person-years of
      observation. Age, sex, type of disease, prior dapsone monotherapy and nerve
      involvement at the commencement of treatment appear to influence the deformity
      incidence. The risk of development of deformity in patients treated with MDT
      appear to be very low and analysis of larger data sets is suggested to
      corroborate the above findings as the information would be useful for planning
      prevention and management of deformity services.

PMID- 7714355
TI  - Comparative assessment of viability of M.leprae by mouse foot-pad and fluorescent
      staining techniques.
AB  - Morphological characteristics have been used as a parameter to assess the
      viability of M.leprae in leprosy patients. However, with the advent of the mouse
      foot-pad technique, viability of M.leprae is determined by growing the bacilli in
      the mouse foot-pad. In recent years, a fluorescent staining technique using
      fluorescent diacetate-ethidium bromide (FDA-EB) has been used to assess the
      viability of cultivable mycobacteria as well as M.leprae. The purpose of this
      study was to compare the viability of M.leprae by both mouse foot-pad and
      fluorescent staining techniques. M.leprae strains from both untreated and treated
      patients as well as mouse passaged strains of M.leprae were used for the
      comparison. Percentage of green-stained bacilli in the inoculum was compared with
      that of multiplication of M.leprae in the mouse foot-pad. It was observed that
      there was no correlation between the estimates of viable M.leprae by fluorescent
      staining and by mouse foot-pad inoculation. FDA-EB staining appears to reflect
      only trends as absence of green staining cells had overall general correlation
      with loss of infectivity to mouse foot-pad but, the converse was not found to be
      true.

PMID- 7714356
TI  - Diagnostic problems of early leprosy in field studies.
AB  - A Series of exercises were undertaken in order to develop methodology for
      consistency and reliability of clinical diagnosis of leprosy under field
      conditions in longitudinal studies. It was observed in initial studies that the
      field investigators could miss about 35% of cases of leprosy, mostly those with
      early manifestations. After training and experience, the proportion of missed
      cases came down to about 20%. In about 14% of females with patches suggestive of
      leprosy the patches were present in the covered areas of the body and so are
      likely to be missed during examination in field situations. One hundred forty two
      individuals with suspicious and definite leprosy lesions detected by paramedical
      workers were examined by a senior medical officer experienced in leprosy on two
      different occasions at an interval of three months for leprosy diagnosis. The
      concordance rates for diagnosis and classification of leprosy were about 80% and
      70% respectively; and corresponding values for kappa were 0.59 and 0.62 similar
      to earlier experiences in inter-observer variation studies.

PMID- 7714357
TI  - Improving patient compliance--a multicentre evaluation of the 'DDS tile test'.
AB  - The feasibility and utility of the "DDS tile test" under field conditions was
      assessed in 112 leprosy centres in Maharashtra. About 10% of the 2952 urine
      samples tested negative for dapsone. Feed back information from 54 centres one
      year later showed that the test could be performed easily under field conditions
      and also that counselling of patients showing poor compliance helped to improve
      drug compliance in over 80% of cases.

PMID- 7714358
TI  - Pathogenesis of generalized nodular type I reaction in a borderline leprosy
      patient.

PMID- 7714359
TI  - Shoreline nails.

PMID- 7714360
TI  - Rehabilitation of leprosy--affected people in Kerala.

PMID- 7714361
TI  - ESCAP/WHQ/ILU workshop on 'Role and responsibilities of the family in the
      elimination of leprosy' 1-4 August 1994, Bangkok.

PMID- 7714362
TI  - State level workshop on "Disability prevention and management" September 24 & 25,
      1994, Hyderabad (A.P.)

PMID- 7714363
TI  - Direct clinical comparison of ultrasound and radiative electromagnetic
      hyperthermia applicators in the same tumours.
AB  - Hyperthermia in conjunction with radiation therapy is a promising method for the
      treatment of superficially or eccentrically located recurrent or advanced primary
      malignant tumours. The external hyperthermia applicators most commonly used are
      radiative electromagnetic (including microwave) or ultrasound devices. Each type
      of device has its own limitations. The aim was to evaluate the temperature
      distributions obtained as well as the acute and subacute toxicities in patients
      that were treated with both radiative radiative electromagnetic and ultrasound
      applicators to the same tumours. Thirty-nine patients treated to 41 hyperthermia
      fields for a total of 197 hyperthermia treatments were analysed. Thermal
      parameter include mean, Tmax, mean Tave, mean Tmin, T50, T90, %T > 43.5 degrees C
      and %T < 41 degrees C. Acute toxicities including pain in field, referred pain,
      blister/ulceration, positional discomfort and subacute toxicities (occurring with
      24 h of treatment) were determined for each type of hyperthermia applicator.
      Although there were increased acute toxicities (in-field or referred pain)
      associated with the ultrasound treatments no significant differences between the
      two methods of heating were observed in temperature distributions or subacute
      toxicities. We conclude that there is no generally preferred method of heating
      superficially or eccentrically located tumours and the type of applicator should
      be selected on a tumour-size and site-specific basis.

PMID- 7714365
TI  - Clinical system for simultaneous external superficial microwave hyperthermia and
      cobalt-60 radiation.
AB  - A system for simultaneous thermoradiotherapy was devised to investigate the
      possible benefits and/or complications of thermal radiosensitization in human
      superficial tumours. The system combines the well-known treatment modalities of
      external 915 MHz microwave hyperthermia and cobalt-60 teletherapy. Single
      waveguide applicators are utilized either attached to blocking trays, so that the
      gamma beam travels through a waveguide and into the patient (en face setup), or
      in a conventional way with the microwave propagation vector orthogonal to the
      gamma beam (orthogonal setup). With these setups a radiation fraction can be
      delivered in the middle of a 60-min, non-interrupted hyperthermia treatment.
      Temperatures and power level are remotely monitored and recorded outside the
      Cobalt room. Extensive measurements and testing showed that the operation of the
      hyperthermia system (generator, applicators, thermometry unit and temperature
      sensors) was not disrupted by irradiation and that the microwaves were confined
      to the treatment room and did not interfere with the operation of the Cobalt
      unit, of an adjacent linear accelerator or of an adjacent radiotherapy simulator.
      For the en face setup the dose distributions induced in solid water phantoms were
      uniform with the exception of a narrow (< 0.5 cm) region under the applicators'
      internal probes where 10-18% reduction exists. This dose defect is clinically
      smoothed using feathering techniques. The system has been successfully used
      without technical problems in 51 treatments in 15 patients (18 lesions) in a
      phase I/II clinical trial. An analysis of the thermal data showed that the
      temperature distributions achieved during simultaneous delivery have the same
      general characteristics of those achieved in conventional sequential hyperthermia
      with microwaves, and that the steady state distributions are maintained during
      the time of simultaneous irradiation. The tests performed in addition to the
      preliminary clinical experience clearly indicate that this type of combined
      therapy is technically feasible and safe. Here the system for simultaneous,
      external, superficial thermoradiotherapy and the implementation tests performed
      are described in detail. Preliminary clinical experience and results are also
      reported.

PMID- 7714364
TI  - A system for the simultaneous delivery of intraoperative radiation and ultrasound
      hyperthermia.
AB  - A multi-element ultrasonic applicator, utilizing an ultrasound reflector, is
      presented which enables the controlled delivery of ultrasonic energy for the
      induction of hyperthermia while allowing the simultaneous application of
      orthovoltage ionizing radiation. A temperature-controlled water circulating
      system allows for acoustic coupling, additional control over the tumour surface
      temperature and depth of maximum temperature into the tissue. In vitro and in
      vivo testing supported the applicators objective of effectively controlling
      temperature elevation. Therapeutic target temperatures of 42 degrees C can be
      achieved within a 5-min period and maintained for a 60-min treatment time. The
      depth of heat penetration could be varied as a function of surface temperature
      and ultrasound frequency. Heating was achieved to at least a depth of 3 cm.
      Radiation measurement methods verified the expected radiation dose uniformity and
      distribution.

PMID- 7714366
TI  - A recommended revision in the RTOG thermometry guidelines for hyperthermia
      administered by ultrasound.
AB  - RTOG thermometry guidelines for clinical trials of hyperthermia using planar
      ultrasound recommended that temperatures be mapped in polyurethane catheters by
      use of single-junction copper-constantan thermocouples. These guidelines were
      based on an assumption that the error in temperature measurement due to thermal
      conduction would generally not exceed +/- 0.3 degrees C. The validity of this
      assumption was tested with a commercially available single-junction copper
      constantan thermocouple. The width of the point spread function, an indicator of
      the relative magnitude of the conduction error, was five times greater than
      expected. As a result, the conduction error is projected to exceed 0.3 degrees C
      in a temperature gradient of only 1.5 degrees C/cm. This projection was confirmed
      by mapping a thermal peak which simulates a typical clinical temperature profile.
      This peak had an amplitude of 6 degrees C, a full-width at half-maximum of 3.5
      cm, and a maximum gradient of approximately 3 degrees C/cm. Temperatures measured
      at 0.5-cm intervals over the span of this peak were in error by a mean of +/- 0.6
      degrees C. It is strongly recommended that the RTOG guidelines be revised to
      replace copper-constantan thermocouples with manganin-constantan single- or multi
      junction thermocouples which will assure that the conduction error will be < +/-
      0.3 degrees C.

PMID- 7714367
TI  - Use of manganin-constantan thermocouples in thermometry units designed for copper
      constantan thermocouples.
AB  - Commercial ultrasound hyperthermia systems typically include thermometry units
      designed for copper-constantan thermocouples. Replacing these copper-constantan
      thermocouples with manganin-constantan thermocouples is advantageous in reducing
      the measurement error caused by the conduction of heat along the copper wire, but
      their performance in these thermometry units is uncertain. The accuracy of
      manganin-constantan thermocouples in the Labthermics LT-100, Clini-Therm
      TS1200/TM100, and Physitemp TM-12 thermometry units was investigated using a
      temperature controlled circulating water bath monitored by a mercury thermometer
      having a calibration traceable to NIST. The results demonstrate that an accuracy
      of +/- 0.2 degrees C can be achieved with manganin-constantan thermocouples over
      the range 35-55 degrees C without hardware modification provided specific
      calibration procedures are followed. With the Labthermics LT-100, a double point
      calibration should be carried out at 35 and 55 degrees C. With the Clini-Therm
      TS1200/TM100, a self-calibration of the unit using its internal calibration well
      plus a single point calibration using an external temperature standard provides
      sufficient accuracy. The Physitemp TM-12 requires an external computer for read
      out and the user must provide additional software to correct for the error by
      either a single or multiple point calibration.

PMID- 7714368
TI  - Effects of hyperthermia and cepharanthin on adriamycin accumulation with changes
      in extracellular pH.
AB  - We compared adriamycin (ADR) accumulation with the intensity of intracellular
      fluorescence of 3,3'-(di-n-hexyl)-2,2'-oxacarbocyanine iodide (NK-2280), an
      indicator of cell membrane potential, after hyperthermia and examined the effects
      of cepharanthin (CEP) on the accumulation of ADR and NK-2280 in wild and ADR
      resistant strains of Ehrlich ascites tumour (EAT) cells. Among wild 0.2 and 1
      microgram ADR-resistant strains of EAT cells, intracellular accumulation of both
      ADR and NK-2280 decreased with an increase of ADR resistance. Hyperthermia at 42
      degrees C and CEP induced a marked increase in accumulation of both ADR and NK
      2280 in the ADR-resistant strains of EAT cells. The increase in ADR accumulation
      by hyperthermia and CEP is possibly due to an increase in the cell membrane
      potential and the inhibition of ADR efflux by CEP respectively. In the wild
      strain of EAT cells, we also evaluated the effect of extracellular pH change on
      ADR accumulation and the cell membrane potential and their alteration by
      hyperthermia and CEP. ADR accumulation decreased as pH decreased, but the cell
      membrane potential was not appreciably affected by pH change so far examined.
      Hyperthermia alone or combined with CEP significantly increased ADR accumulation
      in a pH range from 6.2 to 7.6. Hyperthermia increased the accumulation of ADR in
      the tumour cells, although its pH dependency was not completely resolved. CEP
      enhanced ADR accumulation more markedly in ADR-resistant cells than in wild-type
      cells. Therefore, the combination of hyperthermia and CEP may be very effective
      to increase the ADR cytotoxicity to ADR-resistant tumours.

PMID- 7714370
TI  - Canine bone marrow as a potential thermal sanctuary during the plateau phase of
      41.8 degrees C whole body hyperthermia.
AB  - Whole body hyperthermia (WBH) is currently being evaluated as an adjunct to
      various forms of antineoplastic therapy. In this regard, the uniformity of
      temperature in an individual subject, induced by any given WBH system, is a
      significant factor. Preliminary animal investigations suggested that the bone
      marrow temperature may differ from core temperature during 41.8 degrees C WBH. To
      quantitatively evaluate this possible phenomena, dogs were utilized in
      conjunction with a radiant heat WBH system. It was found that mean bone marrow
      temperature was significantly less than core (i.e. rectal) temperature (p <
      0.001), i.e. 0.27 degree C for the ilium 0.40 degree C for the humerus and 0.95
      degree C for the tibia. The implications of these results to current clinical
      trials are discussed.

PMID- 7714369
TI  - Chronic effect of whole-body hyperthermia combined simultaneously with cis
      diamminedichloroplatinum (II) on normal tissue in rat.
AB  - Long-term effects of cisplatin (DDP) (6 mg/kg) alone at 37 degrees C and DDP (2
      mg/kg) plus whole body hyperthermia 120 min at 41.5 degrees C) on DDP-mediated
      normal tissue toxicities were compared up to 12 months post-treatment using a
      F344 rat model. Acute renal damage, represented by an increase in blood urea
      nitrogen (BUN) at day 5 posttreatment, was significantly higher after DDP (6
      mg/kg) alone at 37 degrees C than the increase in BUN after DDP (2 mg/kg) plus
      whole body hyperthermia. After recovery, BUN levels as a result of both
      treatments remained elevated. From 9 months onwards BUN levels as a result of the
      combined treatment gradually increased to values > 100 mg/dl. At 12 months, side
      toxicities as a result of the combined treatment were more severe than the side
      effects noted after DDP (6 mg/kg) alone at 37 degrees C. Red blood cell and
      hematocrit values were significantly reduced, whereas BUN was significantly
      increased. The results obtained with histological examination of the kidneys
      corresponded with the observed functional differences. Platinum levels in the
      kidney, however, were highest in the DDP (6 mg/kg) alone at 37 degrees C group.
      This observation does not explain why the chronic toxicity as a result of the
      combined modality treatment was more severe.

PMID- 7714372
TI  - Temperature dependence of canine brain tissue diffusion coefficient measured in
      vivo with magnetic resonance echo-planar imaging.
AB  - The intensity of conventional spin-echo diffusion-weighted magnetic resonance
      (MR) images is approximately linearly dependent on temperature over a restricted
      range using conventional diffusion-weighted spin-echo magnetic resonance imaging
      (MRI). However, conventional diffusion-weighted MRI is too motion sensitive for
      in vivo thermometry. The present work evaluated rapid diffusion-weighted echo
      planar imaging (EPI), which is less sensitive to motion, for application to non
      invasive thermometry in acrylamide gel materials and in vivo in canine brain
      tissue for applications in therapeutic hyperthermia. The rapidly switched, strong
      gradients needed for EPI were achieved using a 'local' z-axis gradient coil. Gel
      materials were heated with a small (10 cm diameter) spiral surface microwave (MW)
      applicator at 433 MHz, while in vivo heating was accomplished with whole body RF
      hyperthermia using an annular phased array (130 MHz). The MW or RF fields
      associated with heating and imaging (64 MHz) were decoupled using bandpass
      filters providing isolation in excess of 100 dB. This isolation was sufficient to
      allow simultaneous imaging and MW or RF heating without deterioration of the
      image signal-to-noise ratio. Using this system in a gel, temperature sensitivity
      of the diffusion coefficient was observed to be (3.04 +/- 0.03)%/degrees C which
      allowed temperature changes of 0.55 degrees C to be resolved for a 1.8 cm3 region
      in < 10 s of data acquisition. In vivo, cardiac gating of the pulse sequence was
      necessary to minimize motion artifacts in the brain. The temperature sensitivity
      of brain tissue was (1.9 +/- 0.1)%/degrees C allowing temperature changes of 0.9
      degrees C to be resolved in a 0.9 cm3 volume in < 10 s of data acquisition. We
      conclude that with further optimization of the data acquisition conditions it
      will be possible to determine 0.5 degrees C temperature changes in 1 cm3 volumes
      in < 10 s using this technique.

PMID- 7714371
TI  - Hyperthermic modulation of radiolabelled antibody uptake in a human glioma
      xenograft and normal tissues.
AB  - These experiments investigate the biodistribution of radiolabelled MAb in a human
      glioma xenograft model after 4 h of local hyperthermia (HT) with a twofold
      purpose: to maximize the ratio of cumulative isotope activity in tumour relative
      to normal tissues, and to examine the temperature dependence of the effect.
      Restrained, unanaesthetized athymic nude mice bearing 150-200 mm3 s.c. human
      glioma xenografts (D-54 MG) were given 5 micrograms 125I-labelled specific and
      131I-labelled non-specific MAb immediately prior to HT (water bath) for 4 h.
      Cohorts of five animals were killed at 0, 4, 8, 12 and 24 h after HT, and normal
      and tumour tissues were analysed for activity of each isotope. MAb uptake in
      tumour was greater with HT than with controls, and greater for specific MAb than
      for non-specific MAb. Uptake in thyroid was not significantly affected by tumour
      HT, suggesting that HT does not increase the rate of dehalogenation. Uptake in
      several other normal tissues away from the heated site was significantly
      increased (as were reported previously in mice anaesthetized with pentobarbital
      sodium during treatment; Cope et al. 1990), but the temporal pattern was
      different from that observed in tumour, suggesting that short-lived isotopes
      might lead to preferential dose deposition in heated tumour. Doses to various
      tissues were calculated for isotopes having a range of half-lives; the results
      clearly indicated that maximum differential in uptake between tumour and normal
      tissues would occur for isotopes with half-lives < 3 days. A separate series of
      experiments compared tumour uptake for 40, 42 and 44 degrees C HT. These results
      demonstrated that 42 and 44 degrees C HT created maximum enhancement in specific
      antibody uptake over controls. Specific MAb was retained over time in 42 degrees
      C-heated tumours, whereas significant washout occurred for non-specific MAb,
      which indicates that MAb retention was due to increased specific binding at this
      temperature and not vascular damage with antibody trapping. Retention of both
      specific and non-specific MAb was seen at 44 degrees C, suggesting that vascular
      damage becomes an important non-specific mechanism for antibody retention at
      higher temperatures.

PMID- 7714373
TI  - Phase stability of a clinical phased array system for deep regional hyperthermia.
AB  - Measurements were performed on the amplifiers of a phased array system to
      evaluate the dependence of phase on frequency. The power from the amplifiers was
      terminated into a 50 ohm load at the point of connection to the antennas of the
      applicator, and the power was sampled to determine the phase relation between
      amplifier channels. It was found that the measured phase difference between two
      amplifier channels can: (1) change by as much as 20 degrees with frequency; (2)
      be as much as 12 degrees different than the prescribed phase; and (3) be as much
      as 30 degrees different than the phase measured and displayed by the system.
      Previous studies indicate that in order to accurately plan and deliver treatments
      with this type of device, it is necessary to know the phase relationship of the
      array to within at least 20 degrees. Since the differences as great as 20 degrees
      were obtained under ideal loading conditions, greater differences could result
      during normal (clinical) loading conditions, and these may not be compensated by
      the operator because of the inaccurate values reported by the system itself.
      These findings should be of concern to investigators using these devices since
      they could result in SAR distributions different from those planned and/or
      optimized for a particular patient. It is therefore recommended that the
      measurements such as those reported here also be performed on similar clinical
      devices as a standard quality assurance procedure so that the power steering
      capabilities of these systems can be utilized effectively and safely.

PMID- 7714376
TI  - [Neutrophil elastase in postoperative pleural effusion of patients who had
      undergone pulmonary resections].
AB  - We determined whether activity of neutrophil elastase increases in pleural
      effusion after lobectomy for the neoplasm in the lung. Samples of pleural
      effusion were obtained 3 and 24 h postoperatively and samples of the peripheral
      blood were obtained preoperatively, 3 h, 24 h, and 1 w postoperatively, then the
      neutrophil counts, the levels of neutrophil elastase and alpha 1-antitrypsin by
      enzyme-linked immunosorbent assay, the activity of neutrophil elastase using
      succinyl-(L-alanine) 3-p-nitroanilide were measured. We found that the levels of
      neutrophil elastase increased 170 times greater in pleural effusion than in
      peripheral blood 3 h after lobectomy. However, the levels of alpha 1-antitrypsin
      did not increase in pleural effusion. The activity of neutrophil elastase
      increased to 0.54 +/- 0.1 mumol/min/l in pleural effusion 3 h after lobectomy,
      however the activity of neutrophil elastase was under the sensitivity level of
      detection in the peripheral blood after lobectomy. In conclusion, there is an
      imbalance between the levels of neutrophil elastase and alpha 1-antitrypsin in
      pleural effusion after lobectomy, the imbalance resulting in the increased
      activity of neutrophil elastase which probably is relating to tissue injury in
      the pleural spaces.

PMID- 7714375
TI  - [Left ventricular systolic and diastolic function after mitral valve replacement
      with preservation of posterior chordae tendineae].
AB  - Left ventricular function was compared in 14 patients who underwent mitral valve
      replacement with preservation of the posterior leaflet, chordae tendineae and
      papillary muscle (preserved group) and 14 patients who underwent conventional
      mitral valve replacement (non-preserved group). 99mTc radionuclide
      ventriculography was performed before surgery and one month after surgery. The
      early diastolic filling rate, an indicator of the efficiency of diastolic
      function, was measured. The patients in the non-preserved group showed an
      anteroseptal ejection fraction of 28 +/- 10% before surgery and 32 +/- 10% after
      surgery, an apical ejection fraction (71 +/- 10% vs 73 +/- 16%), and an
      inferolateral ejection fraction (56 +/- 16% vs 53 +/- 16%). The global ejection
      fraction tended to decrease from 56 +/- 9% to 52 +/- 10%. The patients in the
      preserved group showed an anteroseptal ejection fraction of 37 +/- 13% before
      surgery and 43 +/- 19% after surgery, an apical ejection fraction (74 +/- 20% vs
      77 +/- 17%) and an inferolateral ejection fraction (53 +/- 11% vs 68 +/- 16%).
      The global ejection fraction, reflecting improvement in the inferolateral
      ejection fraction, tended to increase from 53 +/- 11% to 58 +/- 11%. The early
      diastolic filling rate for the preserved group was 1.73 +/- 0.43 before surgery
      and 1.05 +/- 0.61 after surgery, while that for the nonpreserved group was 1.59
      +/- 0.24 vs 0.97 +/- 0.48. Although the early diastolic filling rate normalized
      in both groups, there was no significant difference between the two
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714377
TI  - [Clinico-pathological study of preoperative chemotherapy of esophageal cancer by
      combined use of three drugs--cisplatin, 5-FU and leucovorin].
AB  - We compared the clinical and pathological effects of preoperative combination
      chemotherapy using CDDP, 5-FU, and response rate for the primary lesion, an 81.8%
      response rate for intramural metastasis, 100.0% for intraepitherial spread, and a
      low response rate of 40.7% for lymph node metastasis. Pathological examination
      showed a 55.2% response rate for the primary lesion. There were seven cases in
      which the clinical assessment indicated that treatment was effective and
      pathological examination showed that it was ineffective, and three cases in which
      pathological examination showed a better response than clinical assessment. Cases
      showing a better clinical response included in which necrotic cancer lesion had
      disappeared due to absorption by the time of pathological examination, those with
      tumor regrowth after preoperative evaluation, those evaluated as showing a poor
      response due to residual cancer at the margin. Cases showing a better
      pathological response included those having remaining necrotic tissues and those
      having myoma beneath tumor. For intramural metastatic lesions, the pathological
      response rate was 42.9%, being lower than the clinical response rate. Metastasis
      to 209 lymph nodes showed a 23.0% response rate, with the abdominal nodes showing
      a poor response in comparison with those of the cervix and mediastinum. In 26
      patients receiving preoperative radiotherapy, there was a significantly higher
      frequency of such changes as fibrous scar tissue, foreign body giant cells,
      vacuolation of tumor cells, and hyaloid degeneration of the lesion in comparison
      with the group receiving chemotherapy. Another difference was that the
      radiotherapy group showed a higher response of tumors with venous and lymphatic
      involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714374
TI  - Cooled microwave transrectal applicator with adjustable directional beam for
      prostate treatment.
AB  - A new intracavitary applicator design for microwave hyperthermia, particularly
      for transrectal prostate treatment, is presented. It includes an exchangeable
      multisection antenna that enables us to create a required longitudinal heating
      pattern, a cooling system to shift the maximum temperature away from the surface
      and a microwave reflecting system embedded in the cooling system that allows one
      to shape the irradiation beam in a transverse direction. Independent control of
      the longitudinal and transverse irradiation patterns of the applicator along with
      the cooling system, enable precise heating of selected tissues. Results of SAR
      measurements, E-field measurements and steady state temperature distributions, in
      solid and liquid tissue-equivalent phantoms are presented. Clinical performance
      of this applicator was evaluated earlier in patients heated intraoperatively and
      in a phase I clinical study. The applicator was found capable of effectively
      heating a tissue volume extending radially 3-25 mm from the applicator surface,
      angularly defined by configuration of reflecting system and longitudinally
      determined by specific choice of the multisection antenna.

PMID- 7714379
TI  - [Correlation between acute rejection and the role of donor specific cytotoxic T
      lymphocyte in canine lung allotransplantation].
AB  - We investigated the correlation between the donor specific CTL activities and
      pathological findings of the grafted lungs by using mononuclear cells obtained
      from BAL fluids (BAL), peripheral blood (PBL), spleen (SpL) and grafted lungs
      (GIL) in canine lung allotransplantation. Twenty eight mongrel dogs underwent
      left lung allotransplantation. Fifteen dogs were not given immunosuppressive
      drugs. Thirteen dogs were given cyclosporine a 20 mg/kg/day per os for ten days
      postoperatively. Dogs were monitored by chest roentgenograms and cytotoxic
      activity tests of which targets were donor's fibroblasts. Pathological findings
      were classified by Prop's classification. The results were as follows. In latent
      and vascular phases no elevations of cytotoxic activities were demonstrated in
      PBL, BAL and GIL. But in early alveolar phase the cytotoxic activity was elevated
      to 19.83 +/- 14.54% in BAL. In late alveolar phase the highest cytotoxicities of
      30.83 +/- 15.28% in PBL, 72.63 +/- 7.36% in BAL and 70.07 +/- 6.34% in GIL at E:T
      = 100:1 were demonstrated. In pneumonia cytotoxicity did not elevate at all in
      any effectors. As a result of them, it clearly shows that BAL is a good tool for
      the diagnosis of lung rejection.

PMID- 7714378
TI  - [CT measurement of the thoracic density].
AB  - The purpose of this introducing study was to establish the normal lung density
      using computed tomography of the chest. If it is possible to analyze the density
      of normal lung parenchyma, it could be possible to estimate the quantity of
      effective ventilation capacity based on account of the CT number of given range.
      A cross section of the lung, however, is not homogeneous because it contents of
      vascular tissue, interstitial tissue, air and others which have widely variety
      densities. To estimate pulmonary function, it is necessary to know the exact CT
      number of only normal lung tissue. Mean values for varies tissues and areas in
      the thorax were assessed in 34 patients (21 males, 13 females, average age: 58
      years, from August 1987 to June 1993), 18 case of lung cancer (10 preoperative, 8
      postoperative), 5 metastatic lung cancer, 1 giant bulla, 1 aspergilloma, 1
      pulmonary AV fistula, 8 case had no lung disease. The measured normal peripheral
      lung by radiographic appearance on CT images, vascular in the lung, bronchus,
      rib, muscle and fat structured chest wall, heart, liver, aorta, esophagus, and
      thymus. Density of normal peripheral lung tissue was measured in 6 points on each
      slices. These scores were compared left vs. right, slice number, and anterior vs.
      posterior. The CT numbers in this study following the no enhanced computed
      tomography scanner: GE9800 CT by using the regions of interest which limited in
      0.01 cm 2 area. There was no significant difference between left and right lung,
      among different slices, although between anterior and posterior in the normal
      lung.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714381
TI  - [Surgical treatment of 22 primary cardiac myxomas].
AB  - We report surgical treatment of 22 patients with primary cardiac myxomas,
      including 17 left atrial (LA), 3 right atrial (RA), 1 left ventricular and 1
      right ventricular myxomas. Eighteen patients manifested congestive heart failure,
      and an embolic episode was observed in 5 patients preoperatively. Inflammatory
      laboratory findings were observed in 16 patients. One case of RA myxoma was
      complex cardiac myxoma. A transverse biatrial approach was useful for removal of
      large LA myxomas and when the attachment of the tumor was unconfirmed
      preoperatively. There were no hospital deaths. Stroke occurred in 1 and
      supraventricular arrhythmia in 3 patients in the early postoperative period.
      There were 2 late deaths unrelated to cardiac myxomas. No signs of recurrence
      have been observed.

PMID- 7714383
TI  - [Oxygen economy in patients after open heart surgery--effects of cardiopulmonary
      bypass on oxygen metabolism].
AB  - The relationship between oxygen delivery (DO2) and oxygen consumption (VO2) was
      studied in thirty patients who underwent open heart surgery. Delivery dependent
      consumption was observed for the first 48 hours after the surgery even DO2 was in
      a physiological range (> 300 ml/min/m2). VO2 decreased in proportion to a
      decrease in DO2 (VO2 = 0.132 x DO2 + 87.9, R = 0.616, p < 0.001). Oxygen
      extraction rate (ER = VO2/DO2) increased also in proportion to a decrease in DO2
      (ER = -0.385 x DO2 + 51.8, R = -0.722, p < 0.001). These results suggest that
      tissue oxygen demand in the early postoperative period is higher than
      physiological conditions. Factors which directly influenced ER were cardiac index
      (CI) and hemoglobin (Hb) as expressed in the following formulas; ER = -6.05 x CI
      + 51.6 (R = -0.592, p < 0.001), ER = -2.02 x Hb + 56.7 (R = -0.414, p < 0.001).
      This indicates that hypoperfusion and anemia deteriorate oxygen metabolism in the
      early postoperative period. As a monitor of oxygen demand, oxygen saturation of
      mixed venous blood (SvO2) was an useful parameter to indicate the ER (ER = -0.872
      x SvO2 + 91.9, R = -0.969, p < 0.001).

PMID- 7714380
TI  - [Autologous blood transfusion in cardiac surgery over 70-year-old patients].
AB  - We discussed the problems for autologous blood transfusion particularly in the
      preoperative blood donation about the patients over 70-year-old who underwent
      cardiac surgery in contrast with the younger patients. Following results were
      obtained: 1) Because aged patients have the tendency of anemia before
      predonation, full storage of blood donation could not be successed. 2 of 8 over
      70-year-old patients were able to do the preoperative phlebotomy, and their mean
      volume were 355 gram as whole blood. On the other hand, 96% patients in younger
      group were phlebotomized preoperatively, and their mean value of storaged blood
      volume were 757 gram. 2) As the examinations about the iron-related parameters,
      not all aged patients were iron deficiency status. Their reticulocyte counts were
      nearly equal level to the younger group and plasma concentration of
      erythropoietin were higher in the aged patients than that in the younger group.
      These results indicate that erythropoiesis in the bone marrow was deteriorated in
      the aged patients. 3) In aged patients, all of them were required homologous
      blood transfusion at their perioperative terms. We thought that they have had the
      anemia before preoperation and our tolerable, allowable level to the
      postoperative anemia was not lower in the aged patients as against to the younger
      group. 4) We performed the autologous plasma donation with the membranous plasma
      separator added to the whole blood donation. It was easy and safe method, and
      circulatory indices were not changed before and after plasma-separation even in
      the aged patients. These autologous plasma were usefully administered as the
      volume expander postoperatively.

PMID- 7714382
TI  - [Pulmonary embolectomy for massive pulmonary embolism].
AB  - Surgical cases of massive pulmonary embolism remain rare in Japan. To discuss the
      surgical problems, clinical courses of 4 patients who underwent pulmonary
      embolectomy under cardiopulmonary bypass at our hospital for the last six years
      were reviewed. There were 2 men and 2 women; ranging from 41 to 72 years (mean
      age, 63 years), 1 of whom had deep venous thrombosis of the lower extremity as a
      predisposing factor. The initial disease recurred in 2 patients. Shock occurred
      in 3 patients preoperatively, 2 of whom had sudden syncope. Cardiac arrest
      occurred before and during pulmonary arteriography (PAG) in 1 patient. The
      systolic pulmonary arterial pressure rose to between 60 and 80 mmHg in all
      patients except for 1 of whom it was not measured. The diagnosis was established
      in 3 patients by PAG and clinically in the remaining recurrent patient.
      Thrombolysis was not effective in all patients, then pulmonary embolectomy was
      performed between four hours and five days after the onset of the disease. One
      patient with preoperative cardiac arrest died of low output syndrome and severe
      respiratory failure, but 3 survived with clinical improvement. Development of the
      prompt and noninvasive diagnostic procedure, rapid cardiopulmonary support in
      severe cases and an early decision to operate are required to improve the
      operative results. Partial resection of the lung was obliged due to massive
      endobronchial hemorrhage after embolectomy in 1 recurred patient. Compression of
      the lungs and embolectomy using a balloon catheter should be performed carefully
      to prevent injuring pulmonary arteries. Implantation of an inferior vena cava
      filter may be beneficial for the selected patient to prevent recurrence of the
      disease.

PMID- 7714384
TI  - [A case of chronic empyema due to tuberculosis with bronchopleural fistulae
      treated successfully by extraperiosteal air plombage thoracoplasty and
      omentoplasty].
AB  - A 63-year-old man, who had undergone induction of artificial pneumothorax at 20
      years of age as a treatment for right tuberculosis, developed fever and cough. A
      chest X-ray film showed marked pleural effusion in the right chest. Examination
      of sputum and the pleural effusion revealed tubercle bacillus, and right
      tuberculous empyema was diagnosed. At surgery, the right thoracic cavity was
      occupied by empyema, and multiple bronchopleural fistulae were observed. Because
      of the presence of tubercle bacilli in the empyema cavity, extraperiosteal air
      plombage thoracoplasty was insufficient for control of the empyema. Therefore,
      omentoplasty was added. Two months after the operation, the patient was
      discharged in good condition. He has been doing well without any sign of
      recurrence of empyema for the last two years. Although extraperiosteal air
      plombage thoracoplasty is a considerably effective therapy for empyema, its
      curability rate is lower in cases like the present one in which bronchopleural
      fistulae and bacteria are present in empyema cavity, such as our case. We
      consider that our method, extrapriosteal air plombage thoracoplasty with
      omentoplasty, is a reliable one for control of empyema, in patient with high risk
      factors for recurrence, such as bronchopleural fistulae and bacteria in the
      cavity.

PMID- 7714385
TI  - [Solitary plasmacytoma of the rib--a case report and review of Japanese
      literatures].
AB  - A 72-year-old woman with solitary plasmacytoma of the right fifth rib was
      surgically treated. She underwent radical resection of the bony chest wall
      including the right fifth rib, the ribs above and below the involved rib, the
      intercostal muscle, and the parietal pleura. Histological finding of the tumor
      was plasmacytoma of the rib. The type of monoclonal protein was IgG and lamda.
      She is doing well one year and eleven months after surgery without any signs of
      recurrence. Solitary plasmacytoma is rare as compared with multiple myeloma.
      Patients with solitary plasmacytoma originating in the rib have a feasibility of
      operative indication, and radical treatment is expected to be by adequate
      surgical resection. Seventeen cases of solitary chest wall plasmacytoma described
      in the Japanese literature are reviewed.

PMID- 7714386
TI  - [Complete resection of superior mediastinal seminoma, following reconstruction of
      superior vena cava--a case report].
AB  - The patient was a 37-year-old man with superior mediastinal seminoma, which
      invaded the bilateral brachiocephalic vein, superior vena cava, pericardium and
      left lung. These invaded organs were resected with the tumor and a vascular
      reconstruction was performed with EPTFE graft and pericardial patch. EPTFE graft
      was interposed between the left brachiocephalic vein and right atrium. Superior
      vena cava was reconstructed by means of pericardial patch. Histologically, the
      tumor was diagnosed as pure seminoma. He received the prophylactic irradiation
      (45 Gy). Although venography two years after operation demonstrated the
      obstruction of the EPTFE graft and marked stenosis of the pericardial patch, the
      patient remains free from the symptom and is doing well without recurrence 45
      months after operation.

PMID- 7714387
TI  - [Thoracoscopic enucleation of leiomyoma of the esophagus--report of two cases].
AB  - Thoracoscopic enucleation of leiomyoma of the esophagus was successfully
      performed in two cases. This paper mainly describes a 53-year-old man who
      experienced with a slight dysphagia and retrosternal discomfort when moving.
      Esophagoscopy showed a mass beneath normal mucosa located at 26 cm from the
      incisor of the left anterior esophagus. Endoscopic ultrasonography showed a
      sharply delineated low echoic mass with regular echo-pattern, measuring 4 cm
      along the axis. The lesion was diagnosed as leiomyoma. The operation was
      performed under general anesthesia, keeping the patient on the left postero
      lateral position. A double-lumen endotracheal tube was utilized and the right
      lung was collapsed. Six trocars were inserted through right intercostal spaces
      for operation. The azygos vein first of all was dissected and divided by an
      EndoGIA. The esophagus was then mobilized lengthwise enough to rotate the left
      side to the right with two slings traction for better visualization of the lesion
      site. Intraluminal balloon-mounted esophagoscope was useful enough to expose the
      tumor inner side out of the esophageal wall and the tumor was easily enucleated.
      After resection, intact esophageal mucosa was confirmed by endoscopy and the
      proper muscle layer of the esophagus was closed with 2-0 Vicryl. In the 2nd case,
      leiomyoma located at 32 cm from the incisor of the right esophageal wall, 4 x 1.5
      x 1 cm in size, was removed by the same technique using five trocars, where
      neither the azygos vein divided nor the esophagus mobilized. Both patients showed
      uneventful recovery and the symptoms disappeared after operation. Intraluminal
      balloon-mounted esophagoscope was useful to do this kind of thoracoscopic
      procedure.

PMID- 7714388
TI  - [A case of mediastinal fibrosarcoma].
AB  - Mediastinal fibrosarcoma is rare and comprises only 0.18% of mediastinal tumors.
      A case of mediastinal fibrosarcoma is reported. A 57-year-old woman was admitted
      to our hospital with a chief complaint of chest oppression. Computed tomogram and
      magnetic resonance imaging revealed an anterior mediastinal tumor expanding
      beneath the diaphragm. The tumor invaded the pericardium, the left lung and the
      diaphragm, so extensively resected. The resection was non-curative because of the
      presence of bloody pericardial effusion and maligant stump of the pericardium.
      Pathological examination showed fibrosarcoma. Although she recovered well
      postoperatively, she died with recurrence of the tumor, especially direct
      oppression of the heart, 8 months after the operation. In this case adjuvant
      chemotherapy did not effective and noncurative operation did not improve the
      prorhylaxis.

PMID- 7714389
TI  - [A case of a single coronary artery in the presence of coexistent atherosclerotic
      coronary artery disease].
AB  - A 57-year-old female was admitted with 6-month history of effort angina.
      Ascending aortography showed that the right coronary artery (RCA) did not
      originate from the right coronary sinus. Coronary arteriography showed that the
      circumflex branch (CX) continued beyond the crux into the right atrioventricular
      groove to supply marginal branches to the right ventricle, that is, RCA
      originated from the CX at the crux. RCA had the 75% stenosis near the crux. Left
      anterior descending branch (LAD) also had 90% stenosis at segment 6. She did not
      have the additional congenital cardiac anomalies, and underwent coronary artery
      bypass grafting to LAD and RCA without problem.

PMID- 7714390
TI  - [Two cases of successful arterial switch operation for double outlet right
      ventricle associated with straddling and cleft mitral valve].
AB  - We successfully performed an anatomical repair for double outlet right ventricle
      associated with straddling and cleft mitral valve in two patients. In both
      patients position of the anterior and posterior papillary muscles was found to be
      normal. Therefore, all staddled mitral component was detached. The mitral valve
      competency was achieved by suture-closure of the cleft and annuloplasty. This
      procedure facilitated intraventricular re-routing from the left ventricle to the
      pulmonary artery. Then arterial switch was performed. Postoperative course was
      uneventful and no significant mitral valve regurgitation was found in either
      patient postoperatively. This procedure can be a good option in patients with
      double outlet right ventricle associated with straddling mitral valve.

PMID- 7714391
TI  - [Treatment of acute type A aortic dissection with onset of the right coronary
      insufficiency].
AB  - This is a case report of the successful treatment for acute type A aortic
      dissection with onset of the right coronary artery (RCA) obstruction due to
      compression of the dissected lumen. A 50-year-old man, who had been received
      medical therapy for hypertension for seven years, was admitted with profound
      cardiogenic shock. The ECG demonstrated complete A-V block and acute myocardial
      infarction (AMI) of right ventricle and inferior wall. Coronary catheter
      intervention was scheduled because intra-aortic balloon pumping was not
      effective, and arteriogram revealed aortic dissection, coronary insufficiency and
      aortic regurgitation (grade I). Soon after inflation of a perfusion catheter at
      the origin of RCA, elevation of arterial blood pressure and recovery to sinus
      rhythm were brought successfully by the coronary reperefusion. Replacement of the
      ascending aorta involving the intimal tear without surgical closure of RCA
      ostium, aortic valve resuspension and coronary artery bypass grafting with
      saphenous vein to RCA were performed 11 hours after the onset, and the
      postoperative course was uneventful. Although aortic dissection with onset of AMI
      was uncommon, it is suspected that the generalizing of catheter intervention for
      AMI increases awareness of such cases and it is emphasised that the application
      of perfusion catheter as an emergency procedure for the illness like this case is
      useful to preserve hemodinamic stability until the surgical treatment.

PMID- 7714392
TI  - [A rare complication of catheter balloon valvuloplasty of pulmonary stenosis--a
      case report].
AB  - We describe a rare complication which occurred during catheter balloon
      valvuloplasty to the stenosis of the pulmonary artery. A 4-year-old girl with
      cyanosis who was diagnosed as having tetralogy of Fallot, patent foramen ovale
      and Down's syndrome underwent the cardiac catheralisation and angiography.
      Angiography showed the stenosis from outlet of right ventricle to bifurcation of
      the pulmonary artery. We attempted catheter balloon valvuloplasty to the stenosis
      of the pulmonary artery subsequently. We used the PTA catheter (NuMED INC,
      canada), 10 mm in diameter. The balloon was inflated twice (6 atm, 5 sec, 8 atm,
      7 sec) at the bifurcation of the pulmonary artery safely. However, during third
      trial to inflate to 8 atm, it proved impossible to increase pressure to the
      desired level of 8 atm. Blood backed up in the catheter and it became impossible
      to deflate the balloon. We failed to remove the catheter through the left femoral
      vein, so we led the catheter to the right internal jugular vein with a guidewire.
      The catheter was successfully extracted in this way. The proximal connection
      between the balloon and the outer tube was broken and the balloon was compressed.
      To our knowledge, such as complication as this has not reported previously.

PMID- 7714393
TI  - [A case of congenital tracheal stenosis with tracheomalacia due to esophageal
      remnants].
AB  - We report a case of congenital tracheal stenosis with tracheomalacia, which shows
      unique histological findings. A 1056 g male infant was delivered by cesarean
      section for fetal asphyxia at 28 wk of gestation. Immediately after birth, he had
      frequent apneic spells and required intubation and ventilation for 70 days. After
      he was discharged at 240 days of age, he had occasional apneic spells and was
      resuscitated by his family doctor. When he was admitted to our hospital at 11
      months of age, he had a respiratory rate of 32 breaths/min with retractions, and
      auscultation revealed biphasic wheezes. Chest X-ray and bronchoscope examination
      showed a stenotic and malacic section of the upper trachea. When he was 1 year
      and 2 months old, an operation was performed. The diseased portion was resected
      and end-to-end anastomosis with interrupted absorbable suture was performed. The
      postoperative course was uneventful and he was discharged from our hospital on
      the 46th postoperative day. Histologically, the cartilaginous ring was composed
      of some islets of cartilage. Furthermore, there were some striated muscle cells
      on the inside of the incomplete cartilaginous ring. To our knowledge, this
      finding has never been reported in earlier papers. We suppose that some of the
      visceral mesenchymal tissue which should form the esophagus became sequestered in
      the tracheal region before the esophageal and tracheal tubes completely
      separated.

PMID- 7714394
TI  - [A case of surgical repair for the aortic insufficiency due to the tears of the
      aortic cusps during PTCA].
AB  - We report a rare case of aortic insufficiency due to the tears of the aortic
      cusps during percutaneous transluminal coronary angioplasty (PTCA). A 62-year-old
      man successfully underwent simultaneous aortic valve replacement and coronary
      artery bypass grafting. The post operative course was uneventful, and the patient
      was discharged in a stable condition. This report emphasizes the need to consider
      the possibility of acquired aortic insufficiency due to the complication of PTCA.

PMID- 7714395
TI  - [A case report of infective endocarditis complicated with Klippel-Trenaunay-Weber
      syndrome].
AB  - We reported an experience of successful aortic valve replacement due to active
      infective endocarditis complicated with Klippel-Trenaunay-Weber (KTW) syndrome
      which was characterized by limb hypertrophy, hemangioma, arteriovenous fistula
      and varicose veins. A 27-year-old man was admitted to our hospital because of
      severe dyspnea and high grade fever. Echocardiogram revealed severe aortic
      regurgitation and destruction of aortic valve due to active infective
      endocarditis. We performed aortic valve replacement and patch closure of annular
      abscess. As to vascular malformation of lower limb including arteriovenous
      fistula and varicose veins, surgical treatment was not undergone to avoid
      postoperative limb dysfunction. Although the origin of infective endocarditis was
      uncertain, the patient had peripheral vascular malformations. It was postulated
      that valvular endocardial injury might be occurred by cardiac volume overload due
      to arteriovenous fistula. The patients with KTW syndrome should be followed under
      careful observation since infective endocarditis may be one of the complications
      of the syndrome.

PMID- 7714397
TI  - [A case of leiomyosarcoma as a mediastinal tumor excised by bilateral
      thoracotomy].
AB  - Leiomyosarcoma as a mediastinal tumor is so rare that no more than 6 and 12 cases
      have so far been reported in and out Japan, respectively. The patient was 74-year
      old male. While treated at the outpatient clinic of our university hospital for
      low back pain, he was referred to our department because of a shadow of the
      mediastinum on chest roentgenogram. A fist-sized tumor was found located in the
      posterior mediastinum behind the heart. Since it was difficult to make a
      preoperative definitive diagnosis, it was excised by bilateral thoracotomy.
      Histologically, it was compatible with sarcoma and a definitive diagnosis of
      leiomyosarcoma was made based on electron microscopic findings.

PMID- 7714398
TI  - [A case report of annuloaortic ectasia with coarctation of the aorta and "high
      take off" of the right coronary artery].
AB  - A 21-year-old male who had annuloaortic ectasia with coarctation of the aorta and
      "high take off" of the right coronary artery underwent two stage operations. A
      bypass operation using an artificial graft was performed for coarctation of the
      aorta at the first procedure. The second procedure, Cabrol's operation, was
      performed on 83rd day after the first operation. At the second operation we found
      "high take off" of the right coronary artery. The right coronary artery
      originated about five centimeters above the rim of the left sinus of Valsalva.
      Post-operative cause was uneventful. Annuloaortic ectasia combined with
      coarctation of the aorta and "high take off" of the right coronary artery is very
      rare in the literature.

PMID- 7714396
TI  - [A case of acquired von Willebrand disease due to pulmonary stenosis after
      Jatene's operation].
AB  - The case of a 9-year-old girl with pulmonary stenosis complicated by acquired
      bleeding tendency after Jatene's operation is reported. Coagulation study
      revealed that platelet count and von Willebrand factor were reduced.
      Catheterization study revealed severe pulmonary stenosis, the pressure gradient
      between the right ventricle (RV) and pulmonary artery (PA) being 190 mmHg. A link
      between pulmonary stenosis and bleeding tendency was suggested and the patient
      was diagnosed as having acquired von Willebrand disease due to activated
      platelet/von Willebrand factor interactions enhanced by "shear stress" at the
      site of pulmonary stenosis. Right ventricular outflow reconstruction was done
      when she was 9 years-old. Due to a protocol based on the results of the challenge
      test that we instituted to determine the efficacy and effective duration of blood
      derivatives and hemostatic agents, perioperative massive bleeding was avoided.
      Bleeding tendency disappeared and coagulation study findings normalized with
      correction of the abnormal hemodynamic state.

PMID- 7714399
TI  - [A case report of closing aortic dissection with cardiac tamponade which
      developed re-dissection three weeks later].
AB  - A 57-year-old female with hypotension and consciousness disturbance was referred
      to our institute. Echocardiography and plain CT revealed cardiac tamponade, but
      no apparent evidence of aortic dissection was obtained. With sudden onset of
      hypotension, she was immediately operated without information of aortography,
      enhanced CT, and MRI. Approximately 200 g of pericardial hemorrhage and slight
      subadventitial hematoma was grossly found and surface ultrasonography revealed
      the mild localized intramural hematoma (crescent-shaped translucent layer of at
      most 5 mm in width) at the proximal ascending aorta. Because neither false lumen
      with blood flow nor intimal flap was found, pericardial drainage without aortic
      replacement was performed. However, DeBakey type II of aortic dissection with
      wide false lumen was found with CT and MRI within three weeks, and re-operation
      was carried out. The dissection ranged from the ostium of right coronary artery
      to the beginning of innominate artery, but did not involve the coronary arteries
      and major branches of aortic arch. The surface ultrasonography and
      transesophageal echocardiography, as well as preoperative CT and MRI,
      demonstrated that false lumen was thrombosed except at the anterior aspect of mid
      portion of ascending aorta. The ascending aorta was replaced. A careful follow-up
      is mandatory for even a localized intramural hematoma, which can progress into
      aortic dissection in a short period.

PMID- 7714400
TI  - [A successful modified Aubert procedure for transposition of the great arteries
      with a special coronary artery pattern--a case report].
AB  - Transplantation of the coronary arteries is an essential and critical part of the
      arterial switch operation, which is considered to be the treatment for most
      neonate with transposition of the great arteries. The presence of an intramural
      segment of coronary arteries, close coronary ostia adjacent to each other
      increase the risk of coronary twisting and kinking after transplantation. This
      case has an unusual coronary anatomy characterized by two coronary ostia arising
      from the same aortic cusp, intramural segment in a proximal part of the left
      anterior descending coronary artery (LAD) and slit-like narrow ostium of LAD.
      This neonate was successfully operated on using Aubert modification which is the
      arterial switch operation without coronary transplantation. In this method, the
      reconstruction of the new pulmonary trunk must be accomplished by direct
      anastomosis of the posterior wall in order to allow for a growth of pulmonary
      artery. Because of a patch retraction which was used to create its anterior wall,
      pulmonary stenosis may occur. In case of reoperation for pulmonary stenosis, we
      have only to enlarge the anterior part of the pulmonary artery to take down the
      stenosis. Coronary transplantation should be avoided in TGA neonate with an
      unusual coronary anatomy including intramural coronary artery and closed coronary
      ostia adjacent to each other.

PMID- 7714403
TI  - [The 68th Annual Meeting of the Japanese Orthopaedic Association (I). Yokohama,
      April 9-11, 1995. Abstracts].

PMID- 7714402
TI  - A mathematical model of insulin secretion.
AB  - Diabetes mellitus is a chronic state of excessive blood glucose levels
      (hyperglycaemia), which may result from many environmental and genetic factors,
      often acting jointly. The major regulator of glucose concentration in the blood
      is insulin. It is known that about 50% of the insulin is taken up by the liver on
      passing through it after secretion from the pancreas. The precise value of this
      fractional uptake is not known, so the prehepatic insulin secretion rates cannot
      be readily estimated from the plasma insulin concentration levels. By utilizing
      the equimolar secretion of insulin and connecting peptide (C-peptide) from the
      pancreas, a noninvasive method has been formulated. This was based on a
      compartmental model which involved the pancreas, liver, and plasma. The resulting
      differential equation yielded a gamma variate solution which could be readily
      linearized. The model was then tested on 56 normal (51 nonobese and 5 obese)
      subjects, and three groups of subjects with diabetes who could be labelled as
      mild, moderate, and severe (based on the fasting plasma glucose concentration)
      with 83, 88, and 64 subjects respectively. We have focused on the human patient
      environment of the clinician to produce a distinct model which gave a consistent
      pattern within all four groups with good fits between observed and theoretical
      values of the plasma insulin levels. The consequent rates for insulin secretion
      were consistent across the groups and were clinically meaningful.

PMID- 7714401
TI  - The regulation of an age-structured population by a fatal disease.
AB  - A model describing the effect of a fatal disease on an age-structured population
      which would otherwise grow is presented and analysed. If the disease is capable
      of regulating host numbers, there is an endemic steady age distribution (SAD),
      for which an analytic expression is obtained under some simplifying assumptions.
      The ability of the disease to regulate the population depends on a parameter
      R(alpha), which is defined in terms of the given age-dependent birth and death
      rates, and where alpha is the age-dependent disease-induced death rate. If
      R(alpha) < 1 the endemic SAD is attained, while R(alpha) > 1 means the disease
      cannot control the population's size. The number R(0) is the expected number of
      offspring produced by each individual in the absence of the disease; for a
      growing population we require R(0) > 1. A stability analysis is also performed
      and it is conjectured that the endemic SAD is locally asymptotically stable
      whenever it is attained. This is demonstrated explicitly for a very simple
      example where all rates are taken as constant.

PMID- 7714404
TI  - The effect of pilocarpine on ocular levobunolol absorption from ophthalmic
      solutions.
AB  - Studies in vitro and in vivo were conducted to investigate the effect of
      pilocarpine on ocular absorption of levobunolol when both drugs were formulated
      in one solution dosage. The ocular absorption of levobunolol is pH-dependent. Due
      to the large buffering capacity of pilocarpine at pH 5.5, the ocular absorption
      of levobunolol from pilocarpine-containing solutions was reduced by approximately
      four-fold as compared to a non-pilocarpine-containing formulation at pH 7.2. The
      ocular absorption of levobunolol in the presence of pilocarpine at acidic pH was
      enhanced by the use of sulfosuccinates, specifically Schercopol CMS.

PMID- 7714406
TI  - Inhibition of cell adhesion to lens capsule by LCM 1910, an RGD-derived peptide.
AB  - Opacification of the posterior lens capsule, (secondary cataract), is one of the
      major complications of extracapsular cataract extraction. The lens epithelial
      cells remaining after surgery migrate and proliferate along posterior capsule,
      and give rise to structures such as pearls and cells with contractile properties,
      which considerably hamper vision. One pharmacological approach aimed at limiting
      this phenomenon would be to stop this cell migration, thus inhibiting their
      proliferation. It has been shown that cells adhere and migrate on their support
      via adhesion molecules such as integrins. Generally, the tripeptide sequence Arg
      Gly-Asp (RGD) is the recognition motif for these receptors. In this study, cell
      adhesion inhibition in the presence of RGD peptides and derivatives was measured
      on extracellular matrix and lens capsule. One of these compounds, the [N alpha
      acetyl-NG(H+)-arginyl]-glycyl-[C beta (H)-C alpha -benzyl]-aspartamid- HCl] (LCM
      1910), significantly inhibited cell migration at millimolar concentrations, and
      could be of interest in prevention of secondary cataract.

PMID- 7714405
TI  - Prejunctional alpha 2-adrenoceptors and adenylyl cyclase regulation in the rabbit
      iris-ciliary body.
AB  - Agents that elevate intracellular cyclic AMP (cAMP) have been found to enhance
      the synaptic discharge of norepinephrine (NE) from sympathetic nerve terminals in
      the rabbit iris-ciliary body and other peripheral tissues. We explored the
      hypothesis that prejunctional alpha 2-adrenergic receptors that mediate feedback
      inhibition of NE release may be coupled to adenylyl cyclase inhibition. To
      indirectly monitor cAMP changes in sympathetic axon terminals, we analyzed the
      cAMP-mediated activation of tyrosine hydroxylase, a sympathetic marker protein
      that undergoes acute phosphorylation and activation by cAMP-dependent protein
      kinase A. Tyrosine hydroxylase activity was assayed in situ by incubation of
      rabbit iris-ciliary body tissue segments in buffered Krebs-Ringer solution
      containing the substrate tyrosine (100 microM) and the DOPA decarboxylase
      inhibitor brocresine (30 microM). Intraneuronal DOPA accumulation was quantified
      by HPLC with electrochemical detection. Tyrosine hydroxylase activity was
      increased approximately 2 fold by incubation with forskolin (10 microM) plus IBMX
      (0.5 mM) or with 8-Bromo-cAMP (3 mM). Simultaneous addition of the alpha 2
      adrenergic agonist clonidine (1 microM) attenuated the response to
      forskolin/IBMX, but had no effect on the response to 8-Br-cAMP. Clonidine
      mediated inhibition of the forskolin/IBMX response was abolished by treatment of
      tissues with N-ethylmaleimide (NEM), an alkylating agent that inactivates
      pertussis toxin-sensitive G proteins (Gi) that couple receptors to adenylyl
      cyclase inhibition. These findings suggest that prejunctional alpha 2
      adrenoceptors in the rabbit iris-ciliary body are negatively coupled to adenylyl
      cyclase. This mechanism may contribute to autofeedback regulation of NE
      biosynthesis and release.

PMID- 7714407
TI  - Ocular pharmacokinetics of orally administered azithromycin in rabbits.
AB  - Azithromycin was orally administered to Dutch-belted rabbits following
      extracapsular lens extraction in one eye. At various times the animals were
      sacrificed, and serum and ocular tissues were obtained for drug level
      determination by HPLC-EC. Following a single dose, peak levels of drug in ocular
      tissues were measured within 8 hours (cornea > 0.5 micrograms/g [15mg/kg]; > 1.5
      micrograms/g [3Omg/kg]). Highest levels were obtained in iris and ciliary body (
      > 15 micrograms). Measurable tissue levels persisted for at least 120 hours.
      Trough levels increased proportionately during drug multiple dose administration.
      Five days following five daily 15mg/kg doses, corneal levels exceeded 0.5
      micrograms/g, and iris and ciliary levels were higher than 15 micrograms/g.
      Aqueous humor and serum levels were equivalent. Vitreous humor levels, though
      higher than aqueous humor, were consistently < 1 microgram/ml. Extracapsular
      cataract extraction did not significantly affect drug uptake.

PMID- 7714408
TI  - The presence of L-carnitine in ocular tissues of the rabbit.
AB  - Carnitine plays an important role in the metabolism of fatty acids. Its presence
      is considerable in tissues that use fatty acids as an important source of energy,
      such as the heart and skeletal muscle. Free carnitine and acid soluble
      acylcarnitines are present in various tissues of the rabbit eye. The lowest
      concentration of carnitine was observed in the vitreous humor and the highest in
      the lens. The ratio, acid soluble acylcarnitine/free carnitine, was lower in the
      cornea, aqueous humor, vitreous humor and lens, than in iris, ciliary body and
      choroid-retina. The topical administration of carnitine increased both free
      carnitine and acetylcarnitine in cornea, and only free carnitine in aqueous humor
      and choroid retina. Only after intravenous administration, did the levels of free
      and acyl-carnitine increase in the iris and ciliary body. Neither of the two
      carnitine species was changed in vitreous humor. The determination of the
      activity of carnitine acetyltransferase in the eye showed that in the ciliary
      body the values of activity were three times higher than those in the iris and
      choroid-retina. The elevated ratio of acid soluble acylcarnitines with respect to
      free carnitine in iris, ciliary body, choroid-retina as well as the higher
      activity of carnitine acetyltransferase in the ciliary body, suggest that
      carnitine plays an important role in those tissues of the eye where cells of a
      muscular nature are present and may represent, after esterification, an important
      energy reserve.

PMID- 7714409
TI  - Emedastine: a potent, high affinity histamine H1-receptor-selective antagonist
      for ocular use: receptor binding and second messenger studies.
AB  - The antihistaminic agent, emedastine, was tested for its ability to compete for
      [3H]pyrilamine, [3H]tiotidine and [3H]N-methyl histamine binding to rodent brain
      H1, H2 and H3 histamine receptors, respectively. Emedastine exhibited the highest
      affinity for H1-receptors (dissociation constant, Ki = 1.3 +/- 0.1 nM), and was
      considerably weaker at H2- (K1 = 49,067 +/- 11,113 nM) and H3-receptors (Ki =
      12,430 +/- 1,282 nM). These data yielded ratios of 37744, 9562 and 4 for H2:H1,
      H3:H1 and H2:H3 receptor affinities, respectively, thus making emedastine a very
      selective H1-receptor antagonist. The H1-selectivity of emedastine was
      considerably superior to that of pyrilamine (H2:H1, H3:H1 and H2:H3 ratios of
      11887, 12709 and 1, respectively). Similarly, the respective receptor affinity
      ratios for ketotifen (858, 1752, 0.5), levocabastine (420, 82, 5), pheniramine
      (430, 312, 1), chlorpheniramine (5700, 2216, 3) and antazoline (1163, 1110, 1)
      showed these antihistamines to be also markedly less H1-selective than
      emedastine. The potency of emedastine (IC50 = 1.44 +/- 0.3 nM) for antagonizing
      histamine-induced phosphoinositide turnover in human trabecular meshwork cells
      compared well with its binding affinity at the H1-receptor. These data indicate
      emedastine to be a high affinity and high potency histamine antagonist with the
      highest selectivity for the H1-histamine receptor.

PMID- 7714410
TI  - Preclinical efficacy of emedastine, a potent, selective histamine H1 antagonist
      for topical ocular use.
AB  - Emedastine [1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)- benzimidazole
      difumarate] was evaluated for topical ocular anti-histaminic activity in
      histamine and antigen stimulated conjunctivitis models. Concentration-dependent
      inhibition of histamine induced vascular permeability changes occurring in the
      conjunctiva was observed when the time interval between topical ocular
      administration and histamine challenge ranged from 1 min to 8 hr. The calculated
      ED50 values obtained using intervals of 1 min, 30 min, 2, 4 and 8 hr were
      0.0002%, 0.000035%, 0.0029%, 0.019% and 0.19%, w/v, respectively. Comparisons of
      relative potency 30 min post dosing between emedastine and other anti-histamines
      demonstrated that emedastine is equipotent to ketotifen, and 7, 7, 10, 10, 100,
      357, 3333, and 5813 times more potent than brompheniramine, chlorpheniramine,
      clemastine, pyrilamine, levocabastine, pheniramine, diphenhydramine, and
      antazoline, respectively. Emedastine (0.1%) failed to significantly attenuate
      either serotonin or platelet-activating-factor induced vascular permeability
      changes indicating high selectivity for the histamine H1 receptor. In a passive
      conjunctival anaphylaxis model in guinea pigs, significant inhibition of the
      allergic response was observed following topical ocular administration of
      emedastine 5 min or 30 min prior to antigen challenge (ED50s 0.0046% and
      0.00022%, respectively). These data clearly indicate that emedastine has
      potential as a topical ocular anti-histamine for treating allergic
      conjunctivitis.

PMID- 7714411
TI  - Intraocular diclofenac and flurbiprofen concentrations in human aqueous humor
      following topical application.
AB  - Flurbiprofen Na and diclofenac Na, two ocular antiinflammatory agents, were
      investigated to determine the aqueous humor concentrations in the human eye
      following topical application. One hundred sixty-five patients undergoing
      cataract surgery received a single drop of either diclofenac Na or flurbiprofen
      Na at selected times prior to the surgical procedure. Aqueous humor samples were
      aspirated at the beginning of surgery and a sensitive high-performance liquid
      chromatographic assay was used to determine the concentration of the
      antiinflammatory agent in the ocular fluid. Samples were obtained between 10 min
      and 24 hrs after a single instillation of the drug onto the cornea. The highest
      average concentration of diclofenac was 82 ng/ml at 2.4 hrs after instillation;
      concentrations remained above 20 ng/ml for over 4 hrs. Thereafter, between 3 and
      16 ng/ml diclofenac could be assayed through 24 hrs. The highest average
      concentration of flurbiprofen, 60 ng/ml, was found at 2.0 hrs. The last
      detectable flurbiprofen concentration was measured at 7.25 hrs after
      instillation.

PMID- 7714412
TI  - Insulin administration to the eyes of normoglycemic human volunteers.
AB  - Animal studies have shown that insulin eyedrops containing an absorption
      enhancing agent can have a significant effect on blood glucose levels. When
      formulated as a topical solution, insulin might potentially be used to treat or
      augment the treatment of diabetes mellitus in humans. We sought to investigate
      the feasibility of using insulin eyedrops in humans by studying the local
      toxicity and efficacy of insulin administered without surfactant to the eyes of
      healthy volunteers. A prospective, randomized, placebo-controlled, single-masked
      study was conducted in which 8 subjects were given 50 microliters of sterile
      normal saline containing varying insulin concentrations randomized to one eye,
      and 50 microliters of placebo (sterile normal saline) to the fellow eye.
      Subjective ocular irritation was evaluated, and the eyelids, conjunctiva, cornea,
      and anterior chamber were examined objectively with slit lamp biomicroscopy.
      Subjects were evaluated for 2 hours following administration of a single dose of
      insulin. There was no statistically significant difference (P > 0.05) in toxicity
      observed by any parameter evaluated between eyes receiving insulin and placebo.
      No systemic absorption of insulin was observed; blood glucose levels and serum
      immunoreactive insulin levels were unchanged. The results of this study suggest
      that single-dose insulin in concentrations up to 100 U/ml formulated in saline
      has no detectable clinical toxicity to the anterior structures of the human eye.

PMID- 7714414
TI  - A mathematical framework for optimal foraging of herbivores.
AB  - The aim of this paper is to study a model of optimal foraging of herbivores (with
      special reference to ungulates) assuming that food distribution is arbitrary.
      Usually the analysis of foraging of herbivores in the framework of optimal
      foraging theory is based on the assumption of a patchy food distribution. We
      relax this assumption and we construct more realistic models. The main constraint
      of our model is the total amount of food which the animal may eat and the
      currency is the total foraging time. We represent total foraging time as a
      variational expression depending on food eaten and the length of the path. We
      prove that there exists a threshold lambda for food acquisition. More explicitly,
      it exists a positive real number lambda such that, at any point x of the path,
      the animal either eats till the density of food is decreased to the value lambda
      or, if the density of food at x is less than lambda, there it does not eat. We
      discuss the results and emphasize some biologically important relationships among
      model parameters and variables. Finally,we try to give a sound biological
      interpretation of our results.

PMID- 7714413
TI  - Review: implants.
AB  - An implantable sustained release device has been developed to treat chronic
      disorders of the eye. The device, consisting of a central core of drug encased in
      layers of permeable and impermeable polymers, can be implanted subconjunctivally
      or intravitreally. This technique was used to develop a ganciclovir device which,
      when implanted into the vitreous, maintains therapeutic vitreous levels of drug
      for 8 months. Initial studies in patients with cytomegalovirus (CMV) retinitis
      indicate that this treatment may offer better control of the disease and fewer
      side effects than existing therapies. Cyclosporine A devices were prepared for
      the treatment of uveitis. Early data suggests that these devices maintain
      therapeutic levels in the vitreous for approximately 3 years. Work on efficacy
      and toxicity is continuing. Although clinical applications of these devices are
      likely to be restricted to diseases requiring chronic drug therapy, they can be
      used to investigate optimal delivery rates. Subconjunctivally implanted devices
      releasing 5-FU for 12 days maintained filters in cynomolgus monkeys for 3 months.
      Similar devices maintained low intraocular pressure in 75% of high risk filter
      patients.

PMID- 7714416
TI  - Threshold quantities for helminth infections.
AB  - For parasites with a clearly defined life-cycle we give threshold quantities that
      determine the stability of the parasite-free steady state for autonomous and
      periodic deterministic systems formulated in terms of mean parasite burdens. We
      discuss the biological interpretations of the quantities, how to deal with
      heterogeneity in both parasite and host populations, how to incorporate the
      effects of periodic discontinuities, and the relation of the threshold quantities
      to the basic reproduction ratio Ro. Examples from the literature are given. The
      analysis of the periodic case extends easily to 'micro-parasitic' systems.

PMID- 7714417
TI  - Vasculature of the dental pulp of atherosclerotic monkeys: light and electron
      microscopic findings.
AB  - Arteriosclerosis is a pathological condition in which there is a severe luminal
      narrowing of arterioles, resulting in tissue ischemia and necrosis.
      Arteriosclerosis has been reported in the dental pulp of normotensive persons as
      young as 40 yr of age. To date, no corroboration of these findings have been
      published. Our study examined pulp from atherosclerotic monkeys for such changes
      under controlled conditions. The lingual artery and canines from 11
      nonatherosclerotic (control) and 11 atherosclerotic (experimental) cynolmolgus
      monkeys were histologically evaluated with light and transmission electron
      microscopy. Lingual arteries from controls did not exhibit atherosclerotic
      plaques, whereas those of the experimental monkeys did show fibro-foamy plaques.
      However, neither experimental nor control animals exhibited any arteriosclerotic
      alterations in the pulp. Our study concluded that, in this animal model, which
      did demonstrate atherosclerosis in the oral cavity, no similar alterations were
      found in the pulp.

PMID- 7714415
TI  - Finite time blow-up in some models of chemotaxis.
AB  - We consider a class of models of chemotactic bacterial populations, introduced by
      Keller-Segel. For those models, we investigate the possibility of chemotactic
      collapse, in other words, the possibility that in finite time the population of
      predators aggregates to form a delta-function. To study this phenomenon, we
      construct self-similar solutions, which may or may not blow-up (in finite time),
      depending on the relative strength of three mechanisms in competition: (i) the
      chemotactic attraction of bacteria towards regions of high concentration in
      substrate (ii) the rate of consumption of the substrate by the bacteria and (iii)
      (possibly) the diffusion of bacteria. The solutions we construct are radially
      symmetric, and therefore have no relation with the classical traveling wave
      solutions. Our scaling can be justified by a dimensional analysis. We give some
      evidence of numerical stability.

PMID- 7714418
TI  - A histochemical study of the behavior of macrophages during experimental apical
      periodontitis in rats.
AB  - The behavior of macrophages from experimentally induced periapical lesions of
      rats was studied in paraffin sections using nonspecific esterase and a monoclonal
      antibody, ED1. Macrophages were seen near the regularly arranged osteoblasts in
      controls and the detached osteoblasts at the initiation phase of bone resorption.
      In addition, numerous macrophages were widely distributed throughout the
      periodontium at the activation phase of bone resorption. On the other hand,
      macrophages were rarely seen near the bone formation surfaces, but large numbers
      of macrophages were localized in microabscess at the activation phase of bone
      formation. It is suggested that macrophages may play an important role in
      activation of osteoclastic bone resorption and inhibition of complete bone repair
      in bone remodeling during experimental apical periodontitis.

PMID- 7714420
TI  - Evaluation of ultrasonic and sonic instruments for intraradicular post removal.
AB  - Ultrasonic instruments are a valuable asset for removing intraradicular posts
      from root canals before nonsurgical endodontic therapy. The purpose of this study
      was to evaluate the relative efficacy of post removal by ultrasonic and sonic
      devices. Fifty extracted teeth were instrumented and obturated. The canals were
      prepared and Parapost #5 posts were cemented with zinc phosphate cement. The
      teeth were divided into five groups, subjected to ultrasonic or sonic
      instrumentation and the time measured until post removal. Median values in
      minutes for the post extractions in each group were: Cavitron = 6.0, Enac = 8.3,
      and Neosonic = 41.2. Sonic instruments were generally unable to remove the posts.
      The results of this experiment indicate that the Cavitron and Enac ultrasonic
      units are significantly more efficient for removing posts than the Neosonic.
      Sonic instruments were not useful for post removal.

PMID- 7714419
TI  - Effect of restorative procedures on the strength of endodontically treated
      molars.
AB  - Endodontically treated molar teeth are considered susceptible to fracture because
      of loss of tooth bulk. This study evaluated the significance of retaining intact
      marginal ridges and selective cusp coverage in preserving tooth stiffness during
      restoration. Strain gauges were bonded to four cusps of 36 intact extracted human
      lower molars. Teeth were loaded mesially and distally in a closed-loop
      servohydraulic system to measure stiffness. Endodontic access was followed by
      mesio-occlusal or mesio-occluso-distal preparation. Teeth were restored with
      either amalgam (no overlay), amalgam overlay, or gold overlay with partial or
      complete cusp coverage. Relative stiffness was calculated for all test
      conditions. Preserving a marginal ridge in molars did not fully conserve the
      strength of adjacent cusps; selective cusp coverage reinforced only the capped
      cusps; full occlusal coverage with gold or amalgam strengthened all cusps, but
      gold did so more consistently. It is more important to cover cusps than to
      preserve tooth structure (including a marginal ridge) in endodontically treated
      molar teeth.

PMID- 7714422
TI  - A comparison of molar root canal preparations using Flexofile, Canal Master U,
      and Heliapical Instruments.
AB  - There are many instruments and techniques for cleaning and shaping the root canal
      system, but none achieves the ideal preparation, especially in curved canals.
      This study compared the step-back technique, using Heliapical and Flexofiles,
      with the Canal Master technique, using Canal Master U instruments. The Bramante
      method evaluated and compared the results. Final analysis showed that root canals
      prepared with Canal Master U instruments and technique were significantly
      rounder, and had less transportation than those prepared by the Heliapical and
      Flexofiles using the step-back technique.

PMID- 7714423
TI  - The spatial distribution and geographic analysis of endodontic office locations
      at the national scale.
AB  - The major purpose of this article was to quantify and describe the spatial
      distribution of endodontic office locations at the national scale. This study
      consisted of 2858 US American Association of Endodontists member endodontists as
      subjects. Three research questions were developed and explored. The location
      quotient technique, the spatial autocorrelation approach, and the multiple
      regression procedure were the major analytical methods. Major results were as
      follows: the highest concentration (2.09 to 2.62) of endodontic offices per
      100,000 US population was located in just two states, Massachusetts and
      Connecticut; the spatial distribution of endodontic office locations did exhibit
      significant (p < or = 0.05, two-tailed test) spatial autocorrelation. Therefore,
      the spatial distribution of endodontic office locations was nonrandom.
      Individually, the most significant predictor of endodontic office locations was
      the location of general practice dentists (its beta coefficient was 0.960606,
      significant at p < or = 0.0001).

PMID- 7714421
TI  - Interpretation of periapical lesions using RadioVisioGraphy.
AB  - Density and gray-scale changes in radiographs are important visual features the
      clinician uses to evaluate changes in bone pattern. With the advent of a new
      direct digital radiology system, RadioVisioGraphy (RVG), the controlled
      adjustment of contrast is now possible. The purpose of this study was to compare
      RVG's diagnostic potential for detecting periapical lesions with that of
      conventional radiography. Lesions were created in human cadaver specimens and
      radiographed conventionally and with RVG. Images were evaluated by three
      endodontists. Results were: (a) when no lesion existed, conventional radiographs
      were more diagnostic than RVG at a significance level at p < or = 0.05; (b) when
      lesions were enlarged to involve lamina dura and medullary bone, RVG was superior
      at p < or = 0.05; and (c) no difference was found between conventional
      radiography and RVG when the lesion involved cortical bone.

PMID- 7714424
TI  - Adult pulpal diagnosis. I. Evaluation of the positive and negative responses to
      cold and electrical pulp tests.
AB  - This study investigated the positive and negative responses of 1488 teeth in 60
      patients to two electric pulp testers and a cold thermal pulp test. Three
      subgroups of known pulpless or pulpally diseased teeth (teeth receiving root
      canal therapy, teeth with root canal fillings, or teeth with confirmed associated
      apical radiolucencies) were identified and their responses evaluated separately.
      Testing was performed on two tooth surfaces, the facio-occlusal and
      faciocervical, and on all restorations. The gingival tissue of each patient also
      was tested using both electrical tests. The primary findings were: (a) teeth not
      responding to cold and either not responding or responding at readings greater
      than the tissue response to electrical had a high probability of being in the
      known pulpless or pulpally diseased subgroups; (b) the only false positive
      responses to cold in the three subgroups were in multirooted teeth with probable
      vital tissue remaining in at least one canal; and (c) in the three subgroups, if
      the false positive responses to electrical that responded at levels higher than
      the patient's tissue response were considered to be negative responses, the
      difference in false positives between cold and electrical became not
      statistically significant (p = 0.07).

PMID- 7714426
TI  - Mucocele: a potential complication to endodontic surgery.
AB  - Mucocele is not a commonly observed complication of endodontic surgery. A case is
      reported of a mucocele forming in the incision line following periapical surgery.

PMID- 7714425
TI  - Small cell carcinoma of the lung metastatic to the wall of a radicular cyst.
AB  - This case report details the unusual presentation of small cell carcinoma at the
      periapex of a maxillary left lateral incisor. The initial clinical presentation
      was that of a symptomatic, nonhealing, well-circumscribed radiolucency about the
      periapex of the tooth. The biopsy specimen submitted by the endodontist was
      diagnosed as small cell carcinoma. This report stresses the need for submission
      of all tissue removed from the oral cavity for histopathological examination.

PMID- 7714427
TI  - Comparison of the sealing capacity of three endodontic filling techniques.
AB  - This study compared the sealing capacity of three different endodontic gutta
      percha filling techniques. Forty-seven upper central incisors with straight
      canals were instrumented and randomly divided into three equal groups of 14. An
      additional group of five teeth with unobturated canals served as positive
      controls. The following gutta-percha filling techniques were evaluated: Trifecta
      (group A), lateral condensation (group B), and a combination of SuccessFil gutta
      percha and lateral condensation (group C). Tubli-Seal was used as a sealer. The
      teeth were radiographed in mesiodistal and bucco-lingual directions to study the
      quality of the filling. Afterward, the teeth were immersed in India ink and
      subsequently cleared. The maximal depth of penetration was measured using a light
      microscope. The mean value of ink penetration for group A was 1.073 mm, for group
      B was 0.522 mm, and for group C was 0.765 mm. No statistically significant
      differences were seen among groups (p < 0.05).

PMID- 7714428
TI  - Effect of super-EBA as a root end filling on healing after replantation.
AB  - The effect of Super-EBA cement as a root-end filling placed in teeth before
      replantation was examined in eight molar roots in monkeys. After extraction, root
      ends were resected, the canals contaminated with oral bacteria, root-end cavities
      prepared, and fillings of Super-EBA placed before replantation. After 8 wk, the
      jaws were removed and prepared for histological examination. The tissue response
      to Super-EBA was very mild, with only a few inflammatory cells being observed at
      the root end of 3 of the 8 roots filled. Previous work showed a similarly mild
      response to Intermediate Restorative Material and a very much more severe
      response to amalgam. It is concluded that the tissue response to Super-EBA as a
      root-end filling is acceptable and considerably more favorable than that to
      amalgam.

PMID- 7714429
TI  - Effects of antibacterial capping agents on dental pulps of monkeys mechanically
      exposed to oral microflora.
AB  - The effects of antibacterial drugs on bacterially contaminated dental pulps were
      investigated in monkeys. Class V buccal cavities with pulpal exposures were
      prepared and then left open to the oral environment for 24 h. The exposed pulps
      were capped with alpha-tricalcium phosphate (alpha-TCP) containing a mixture of
      antibacterial drugs. Either alpha-TCP or Ca(OH)2 was used as a control. Pulpal
      responses were histologically evaluated after 4 wk. Those teeth capped with alpha
      TCP alone showed total pulp necrosis and bacterial growth within the pulp
      chamber. By contrast, the pulps capped with alpha-TCP containing mixed
      antibacterial drugs remained almost normal without any necrotic layer, but showed
      persistent absorbing response to capping materials and no signs of hard tissue
      barrier formation. In teeth capped with Ca(OH)2, a hard tissue barrier was formed
      below the exposure site, with a wide loss of pulp tissue. No inflammation was
      seen under the barrier. These results indicate that mixed antibacterial drugs
      added to alpha-TCP effectively disinfected pulpal lesions, without destroying any
      of the sound pulp tissue. However, hard tissue barrier formation was delayed by
      this mixture as compared with Ca(OH)2.

PMID- 7714430
TI  - Isolation of methicillin-resistant staphylococci in the dental operatory.
AB  - The state of contamination by methicillin-resistant Staphylococci, including
      methicillin-resistant Staphylococcus aureus (MRSA) at the conservative dentistry
      section of the School of Dentistry, Aichi-Gakuin University, was investigated.
      Methicillin-resistant coagulase-negative Staphylococci (MRCNS) were detected in 8
      (20.5%) of 39 dental staff (28 dentists, 8 dental hygienists, and 3 dental
      assistants), but MRSA was not detected. MRCNS was also detected in locations such
      as the dental chair, dental bracket, dental cabinet, and floor, as well as in
      airborne samples. The presence of the same strain in both the oral cavity of
      staff persons and the dental chair/floor locations was determined by biochemical
      properties, antibiotic sensitivity tests, and electrophoretic patterns.

PMID- 7714431
TI  - A comparison of four instrumentation techniques on apical canal transportation.
AB  - The ability of four instrumentation techniques to enlarge and maintain the
      central axis of 51 curved canals was evaluated radiographically. Curved canals in
      extracted human teeth were instrumented using a step-back preparation with K
      files, crowndown preparation with K-files, sonic instrumentation with Shaper
      Sonic files, and the NiTiMatic preparation system. Following coronal preflaring,
      each canal was instrumented to a #35 file 1 mm from the anatomic foramen.
      Radiographs were taken with mercury filling the canal system using a specially
      designed model that allowed for the pre- and postinstrumentation canal to be
      viewed on the same radiograph. Canal enlargement and apical transportation
      resulting from the various instrumentation techniques were evaluated using
      computer analysis. No statistically significant differences were found for canal
      transportation. Sonic instrumentation significantly increased coronal flaring.
      The crown-down and sonic techniques produced more ledges. Elbow formation was
      associated with all instrumentation techniques. The model system developed for
      this study provided an accurate method of assessing the preparation techniques
      and the instrument effects on the canal walls.

PMID- 7714432
TI  - The mandibular incisor: rethinking guidelines for post and core design.
AB  - In post and core research, little attention has been given to the tooth with
      minimal bulk and mesialdistal width. The purpose of this in vitro study was to
      investigate retention and fracture characteristics of lower incisors restored
      with variable dowel designs. Fifty freshly extracted mandibular incisors were
      endodontically treated. Four groups of 10 teeth, decoronalized and dowel- and
      core-restored, were tested for retention characteristics and fracture resistance.
      One group of 10 teeth restored with composite resin in intact natural crown acted
      as controls. Dowel variables included a prefabricated round cross-sectional
      design and a morphologic dowel that reproduced the canal space. A universal
      testing machine created tensile and transverse loads, and failure was measured
      and recorded. Results showed no difference in resistance to transverse loading
      between morphological and standardized dowels (p > 0.05). However, when analyzing
      modes of failure, ferruled morphological post and core design was less likely to
      result in a catastrophic root or post fracture. In addition, morphological dowels
      were significantly more retentive than standardized round dowels in teeth with
      narrow cross-sections (p = 0.007). This study also reaffirmed the findings of
      previous investigations, that the intact natural crown of an endodontically
      treated tooth provides maximum resistance to root fracture.

PMID- 7714433
TI  - Canal configuration of the mesiobuccal root of the maxillary second molar.
AB  - The purpose of this study was to investigate the canal configuration in the
      mesiobuccal root of the maxillary second molar. The canal configuration of the
      mesiobuccal root of the maxillary second molar need not be the same as that of
      the maxillary first molar. Several studies have been attempted to clarify the
      configuration of the second molar, usually via postoperative evaluation,
      sectioning, or radiography. To follow more closely the clinical procedure, this
      study involved access cavity preparation and radiographs taken with files in
      place. Of the 73 extracted maxillary second molars investigated, 67 teeth (91.8%)
      had 3 roots whereas 6 teeth (8.2%) had 2 roots. In the three rooted teeth, the
      mesiobuccal roots of 40 (59.7%) were classified as type I (single canal from
      orifice to apex), 14 (20.9%) were type II (two canals merging short of the apex
      into a single canal at the apex), 11 (16.4%) were type III (two separate and
      distinct canals from orifice to apex), and 2 (3%) were type IV (single canal at
      the orifice, dividing in midroot into two canals exiting at the apex).

PMID- 7714434
TI  - Effects of a carbon dioxide laser on human root dentin.
AB  - The effects of the Luxar LX-20 CO2 dental laser on resected apical root dentin
      were examined using stereomicroscopy and scanning electron microscopy. The
      surfaces of 2-mm-thick sections of dentin from freshly extracted human teeth were
      exposed to CO2 laser radiation. Fluences used ranged from 2.1 to 625.0 J/cm2. The
      effects of the laser energy on the dentin ranged from no visible effects, to
      charring, cracking, cratering, and glazing. The most dramatic effect was
      cracking. Cracking was evident on all specimens having any visible modification
      of the dentin. A prototype-curved laser tip was used and compared with a standard
      straight tip. The curved tip did not deliver laser energy to the dentin as
      efficiently as a straight tip. CO2 laser radiation did not consistently
      obliterate dentin tubules.

PMID- 7714435
TI  - Surgical apical repair with super-EBA cement: a one-visit alternative treatment
      to apexification.
AB  - This article presents an alternative one-visit treatment to conventional
      apexification. Time, patient compliance, and multiple office visits are required
      to complete an apexification successfully. In the technique described, the root
      canal system is instrumented and filled followed by immediate periradicular
      manipulation and apical repair with Super-EBA cement. Cases presented in this
      pilot study have a recall period ranging from 5 to 14 months. It is our
      contention that the results of this technique are highly predictable, with the
      added advantage that unsalvageable situations (e.g., vertical root fracture) can
      be assessed right away. In both instances, the patient will receive the precise
      prognostic assessment and treatment. Thus, patients are returned to their
      restorative dentists with minimal delay.

PMID- 7714436
TI  - Microleakage through dentin after crown cementation.
AB  - This study investigated the relationship between type of luting cement for
      artificial crowns and microleakage through dentinal tubules. Standardized
      preparations were made on intact human premolars, and crowns were made in a base
      metal alloy using conventional techniques. The castings were randomly assigned to
      the following luting agent groups: zinc phosphate (ZP), polycarboxylate (PC),
      glass ionomer (GI), phosphate ester composite resin (GMA/PE), and a composite
      resin with a NPG-GMA dentin bonding agent (GMA/NPG). Then they were cemented in a
      standardized manner. The specimens were artificially aged, stained, sectioned,
      and microleakage occurred through dentinal tubules toward the pulp measured. The
      rank in order from least to most (best to worst) leakage was GMA/NPG, GI, GMA/PE,
      PC, and ZP. Material GMA/NPG recorded significantly less leakage than all other
      materials. Therefore, the results of this study suggest that material GMA/NPG may
      reduce pulpal sensitivity and pathosis.

PMID- 7714437
TI  - Cuspal deflection in molars in relation to endodontic and restorative procedures.
AB  - The extent of cuspal flexure following endodontic and restorative procedures has
      important consequences for potential fracture. This study was undertaken to
      determine the extent to which cusps of molars are weakened by progressively
      larger restorative preparations and endodontic access. Cuspal flexure of 13
      extracted, intact human mandibular molars was measured under controlled occlusal
      loading. A ramped load of 100 N was applied to the mesial cusps via a steel
      sphere, using a closed-loop servohydraulic testing machine. Lateral cuspal
      displacement was recorded by linear measuring devices (direct current
      differential transformers) accurate to 1 micron. Increasingly extensive MO or MOD
      cavity preparations followed by endodontic access were cut in each tooth. Cuspal
      deflection increased with increasing cavity size and was greatest following
      endodontic access. Cuspal deflections of more than 10 microns were observed.
      These findings reinforce the importance of cuspal coverage to minimize the danger
      of marginal leakage and cuspal fracture in endodontically treated teeth.

PMID- 7714438
TI  - Ability of bacterial endotoxin to diffuse through human dentin.
AB  - An in vitro system was developed to determine whether bacterial endotoxin is
      capable of diffusing through dentin without the use of filtration pressure.
      Cavities were prepared in five third molar teeth in order to produce a split
      chamber device consisting of occlusal and pulpal chambers with 0.5 mm of
      intervening dentin. Endotoxin was introduced into the occlusal chamber and the
      effluent in the pulpal chamber was sampled every 30 min for 5 h and at 24 h using
      the limulus lysate assay. In four specimens the initial appearance of endotoxin
      in the effluent ranged from 15 min to 4 1/2 h. In two specimens the concentration
      of endotoxin in the effluent leveled off in 4 1/2 and 5 h, respectively, whereas
      in another two the concentration continued to increase throughout the experiment.
      In one specimen no endotoxin was detected. The results indicate that endotoxin is
      capable of passing through 0.5 mm of dentin.

PMID- 7714439
TI  - A comparison of tissue reactions to Ketac-Fil and amalgam.
AB  - The objective of this study was to compare the bone tissue reactions of Ketac-Fil
      to the most commonly used retrograde filling material, amalgam, in a rat model.
      Forty-eight Harlan rats were divided into three groups: amalgam, Ketac-Fil, and
      controls. Following anesthesia, the right lower incisor was extracted from each
      animal. A 3-mm long x 1-mm diameter polyethylene tube filled with amalgam or
      Ketac-Fil was implanted in the extraction site. The animals were killed at 14,
      42, and 90 days; and the mandibles were dissected en block and processed
      histologically. The inflammatory reaction was assessed by the number of plasma
      cells, lymphocytes, polymorphonuclear neutrophils, giant cells, and osteoclasts
      within 100 microns of the implant. Bone formation was determined as either
      present or absent in the same area. There was no statistically significant bone
      apposition within 100 microns of the Ketac material, and there was a
      statistically significant increase in inflammation in the amalgam group. This
      study indicates that both Ketac-Fil and amalgam are relatively biocompatible, and
      provides support for clinical usage tests of Ketac-Fil as a retrograde filling
      material.

PMID- 7714440
TI  - Bacterial invasion into dentinal tubules of human vital and nonvital teeth.
AB  - The difference in resistance to bacterial invasion into the dentinal tubules
      between vital and nonvital teeth has not been determined. This study was
      conducted to clarify the effect of vital pulp on bacterial invasion into the
      dentinal tubules. The specimens were 19 intact pairs of bilateral upper third
      molars of 19 healthy, young adult male volunteers. In each case, 30 or 150 days
      before extraction, pulpectomies and root canal fillings were carried out
      unilaterally and a class V cavity involving the dentin was made on the palatal
      surface of both the pulpectomized tooth and the nonpulpectomized opposite tooth.
      The cavities were left unprotected to expose them to oral flora until the
      extractions were done, and the extracted teeth were examined histologically. When
      extraction followed 150-day exposure to the oral flora, there was a statistically
      significant difference in the bacterial invasion rate between the vital and
      nonvital teeth. It was postulated that vital teeth were much more resistant to
      bacterial invasion into the dentinal tubules than were nonvital teeth, thereby
      suggesting that the vital pulp plays some important role in this process.

PMID- 7714441
TI  - Leakage of amalgam and Super-EBA root-end fillings using two preparation
      techniques and surgical microscopy.
AB  - An in vitro dye leakage study was conducted to test the root-end sealing ability
      of amalgam with varnish or Super-EBA using two root-end preparation techniques
      and surgical microscopy. Sixty-four single-rooted teeth were instrumented and
      obturated with gutta-percha. Teeth were randomly placed into four groups. Two
      groups received perpendicular root-end resections, 3-mm-deep ultrasonic root-end
      preparations, and either amalgam with varnish or Super-EBA root-end fillings. The
      other two groups received beveled root-end resections, 3-mm-deep micro-handpiece
      preparations, and either amalgam with varnish or Super-EBA. All root-end
      procedures were performed at x5 to x8 magnification. Micro-leakage was assessed
      at 4 months using methylene blue dye and a passive hydrostatic pressure
      technique. Statistical analysis showed that, regardless of technique, Super-EBA
      leaked significantly less than amalgam with varnish. There was no significant
      difference between the two root-end resection and preparation techniques.

PMID- 7714442
TI  - Quantitative assessment of dentin bridge formation following pulp-capping in
      miniature swine.
AB  - A quantitative assessment of dentin bridges was conducted on sections prepared
      from teeth capped with four pulp-capping agents (Bioglass, Life, Demineralized
      Dentin Matrix, and Teflon) in a micro-swine model. The degree of mineralization
      of the dentin bridges relative to the adjacent primary dentin was measured using
      a computer-based image analysis of microradiographs prepared from the sections.
      The rate of formation of the dentin bridge was measured from fluorescent bands
      formed in the same sections by a Demeclocycline dentin marker. There were no
      statistically significant differences in the relative mineral densities of the
      dentin bridges and the rate of dentin bridge formation under the four pulp
      capping agents. These findings support the suggestion that components of the
      extracellular matrix rather than pulp-capping agents may be important in the
      formation and mineralization of dentin bridges in repairing dental pulps.

PMID- 7714443
TI  - Effects of Nd:YAG laser on the permeability of root canal wall dentin.
AB  - The effects of a thermally cooled pulsed Nd:YAG laser on the permeability and
      structural appearance of the root canal wall were investigated in vitro. Twenty
      specimens of freshly extracted human teeth were prepared by conventional methods.
      The teeth were randomly divided into two groups. Group 1 teeth were prepared
      conventionally but not lased. Group 2 specimens received three 15-s laser
      exposures totaling 45 s duration within the root canal via optical fiber
      delivery. Laser parameters were set at 5 W, 50 Hz, using a simultaneous air/water
      coolant spray of 10 psi air and 2 psi water. The external surfaces of the teeth
      were sealed with acrylic and placed in 2% methylene blue dye for 24 h. The teeth
      were then sectioned, photographed, and compared under light microscope for the
      extent of dye penetration. The specimens were subsequently prepared for scanning
      electron microscopy for correlation of permeability measurements with surface
      modifications. The combined use of scanning electron microscopy and dye
      permeability measurements revealed a sealing of the dentinal wall by deposition
      of glass-like material and, in one specimen, the bridging of a lateral canal that
      partially occluded the canal. Based on statistical comparisons, permeability of
      laser-treated teeth was significantly less than untreated specimens (alpha =
      0.005).

PMID- 7714444
TI  - Root canal preparation using the second harmonic KTP:YAG laser: a thermographic
      and scanning electron microscopic study.
AB  - Thermal and microstructural events resulting from KTP laser use during root canal
      preparation were investigated in 30 extracted single-rooted human teeth. In the
      first section of this study, thermal events occurring on the root surfaces of 18
      teeth during and after exposure of the root canal were measured using
      thermography. A variety of parameters were used to determine settings that would
      be effective without causing thermal damage to the periodontal ligament. In the
      second section of the study, root canals of 12 teeth exposed to KTP laser
      irradiation at parameters derived from section 1 were evaluated using Scanning
      electron microscopy. KTP laser application at a power setting of 3 W, an exposure
      time of 2 s, and a frequency of 5 Hz, applied five times, removed smear layer and
      debris from the root canal surface at temperatures below the thermal injury
      threshold for periodontal tissue.

PMID- 7714445
TI  - Effect of preflaring on tactile detection of the apical constriction.
AB  - The efficacy of tactile detection of the apical constriction in flared and
      nonflared root canals was examined in 120 root canals of adult patients. In 68
      nonflared (group 1) root canals, a #15 or #20 K-file was used to detect ("feel")
      the apical constriction. In 52 teeth (group 2), Hedstrom files, Gates Gliden
      drills #2 to #4, and ultrasonic files were used to enlarge the canal orifice and
      flare the coronal portion of the root canals before testing the apical
      constriction. After placing a #15 or #20 file in each root canal, a radiograph
      was taken, and the distance between the tip of the file and the radiographic apex
      was measured. The location of the file tip was classified into three categories:
      (a) within 1 mm short of the radiographic apex; (b) underextended, more than 1 mm
      short of the radiographic apex; and (c) overextended beyond the radiographic
      apex. In group 1 (nonflared), 32.3% of the root canals were classified in
      category a, as compared with 75.0% in group 2 (preflared). Over 26% of the root
      canals in group 1 and approximately 4% of the canals in group 2 were included in
      category b. Files inserted in preflared root canals had a significantly lower
      incidence of overextension than those placed in nonflared canals (21% versus
      41%). The ability to determine the apical constriction by tactile sensation was
      significantly increased when the canals were preflared (p < 0.0001).

PMID- 7714446
TI  - An alternative treatment for the severely resorped maxillary lateral incisor: a
      sequela of ectopic eruption.
AB  - At times dental crowding, maxillary arch inadequacy, or an abnormal lingual or
      horizontal position restricts the eruption of the maxillary cuspid. This ectopic
      eruption can cause the canine to compress the blood supply to the periodontal
      tissues of the adjacent lateral incisor. If undiagnosed and untreated,
      physiological and chemical changes are induced, and the lateral root undergoes
      resorption. When the resorption is severe enough to endanger the retention of the
      lateral, an endeosseous stabilizer can be placed through the root and extended
      into the bone to stabilize the tooth artificially. Two cases demonstrate the
      technique and success of such treatment.

PMID- 7714447
TI  - Most directed forgetting in pigeons can be attributed to the absence of
      reinforcement on forget trials during training or to other procedural artifacts.
AB  - In research on directed forgetting in pigeons using delayed matching procedures,
      remember cues, presented in the delay interval between sample and comparisons,
      have been followed by comparisons (i.e., a memory test), whereas forget cues have
      been followed by one of a number of different sample-independent events. The
      source of directed forgetting in delayed matching to sample in pigeons was
      examined in a 2 x 2 design by independently manipulating whether or not forget
      cue trials in training ended with reinforcement and whether or not forget-cue
      trials in training included a simultaneous discrimination (involving stimuli
      other than those used in the matching task). Results were consistent with the
      hypothesis that reinforced responding following forget cues is sufficient to
      eliminate performance deficits on forget-cue probe trials. Only when
      reinforcement was omitted on forget-cue trials in training (whether a
      discrimination was required or not) was there a decrement in accuracy on forget
      cue probe trials. When reinforcement is present, however, the pattern of
      responding established during and following a forget cue in training may also
      play a role in the directed forgetting effect. These findings support the view
      that much of the evidence for directed forgetting using matching procedures may
      result from motivational and behavioral artifacts rather than the loss of memory.

PMID- 7714448
TI  - Conditioned reinforcement and choice with delayed and uncertain primary
      reinforcers.
AB  - In an adjusting-delay choice procedure, pigeons could peck on either a red key or
      a green key. A peck on the red key always led to a delay associated with red
      houselights and then food. The delay was adjusted over trials to estimate an
      indifference point--a delay at which the two keys were chosen about equally
      often. In some conditions, a peck on the green key led to food on all trials
      after delays of either 10 s or 30 s, and green houselights were lit during the
      delays. In other conditions, food was presented on only half of the green-key
      trials. If the green houselights continued to occur on both reinforcement and
      nonreinforcement trials, preference for the green key always decreased.
      Preference for the green key also decreased if half of the trials had 30-s
      houselights followed by food and the other half had no green houselights and no
      food. However, preference for the green key actually increased if half of the
      trials had 10-s green houselights followed by food and the other half had no
      green houselights followed by no food. The latter condition therefore
      demonstrated a case in which preference for an alternative increased when food
      was removed from half of the trials. The results suggest that the red and green
      houselights served as conditioned reinforcers. A hyperbolic decay model (Mazur,
      1989) provided good predictions for all conditions by assuming that the strength
      of a conditioned reinforcer is inversely related to the total time spent in its
      presence before food is delivered.

PMID- 7714449
TI  - Visual search by chimpanzees (Pan): assessment of controlling relations.
AB  - Three experimentally sophisticated chimpanzees (Pan), Akira, Chloe, and Ai, were
      trained on visual search performance using a modified multiple-alternative
      matching-to-sample task in which a sample stimulus was followed by the search
      display containing one target identical to the sample and several uniform
      distractors (i.e., negative comparison stimuli were identical to each other).
      After they acquired this task, they were tested for transfer of visual search
      performance to trials in which the sample was not followed by the uniform search
      display (odd-item search). Akira showed positive transfer of visual search
      performance to odd-item search even when the display size (the number of stimulus
      items in the search display) was small, whereas Chloe and Ai showed a transfer
      only when the display size was large. Chloe and Ai used some nonrelational cues
      such as perceptual isolation of the target among uniform distractors (so-called
      pop-out). In addition to the odd-item search test, various types of probe trials
      were presented to clarify the controlling relations in multiple-alternative
      matching to sample. Akira showed a decrement of accuracy as a function of the
      display size when the search display was nonuniform (i.e., each "distractor"
      stimulus was not the same), whereas Chloe and Ai showed perfect performance.
      Furthermore, when the sample was identical to the uniform distractors in the
      search display, Chloe and Ai never selected an odd-item target, but Akira
      selected it when the display size was large. These results indicated that Akira's
      behavior was controlled mainly by relational cues of target-distractor oddity,
      whereas an identity relation between the sample and the target strongly
      controlled the performance of Chloe and Ai.

PMID- 7714450
TI  - Neuromodulation by 5-hydroxytryptamine in the antennal lobe of the sphinx moth
      Manduca sexta.
AB  - Using intracellular recording techniques, we have begun to examine the effects of
      5-hydroxytryptamine (5-HT) on antennal-lobe (AL) neurones in the brain of the
      adult moth Manduca sexta. 5-HT modulated the responses of local interneurones and
      projection neurones, which were recognized on the basis of well-established
      electrophysiological criteria, to primary synaptic input elicited by electrical
      stimulation of the ipsilateral antennal nerve. 5-HT applied at low concentration
      (10(-8) mol l-1) reduced the excitatory responses evoked by electrical
      stimulation of the antennal nerve, whereas at high concentration (10(-4) mol l
      1), 5-HT enhanced the responses. At 10(-4) mol l1, 5-HT increased cell input
      resistance, led to broadening of action potentials and caused increased cell
      excitability in many AL neurones.

PMID- 7714451
TI  - Modulatory effects of 5-hydroxytryptamine on voltage-activated currents in
      cultured antennal lobe neurones of the sphinx moth Manduca sexta.
AB  - The modulatory effects of 5-hydroxytryptamine (5-HT or serotonin) on voltage
      gated currents in central olfactory neurones of the moth Manduca sexta have been
      examined in vitro using whole-cell patch-clamp recording techniques. Central
      olfactory neurones were dissociated from the antennal lobes of animals at stage 5
      of the 18 stages of metamorphic adult development. The modulatory actions of 5-HT
      on voltage-activated ionic currents were examined in a subset of morphologically
      identifiable antennal lobe neurones maintained for 2 weeks in primary cell
      culture. 5-HT caused reversible reduction of both a rapidly activating A-type K+
      current and a relatively slowly activating K+ current resembling a delayed
      rectifier-type conductance. 5-HT also reduced the magnitude of voltage-activated
      Ca2+ influx in these cells. The functional significance of 5-HT-modulation of
      central neurones is discussed.

PMID- 7714452
TI  - Moving cheaply: energetics of walking in the African elephant.
AB  - Large animals have a much better fuel economy than small ones, both when they
      rest and when they run. At rest, each gram of tissue of the largest land animal,
      the African elephant, consumes metabolic energy at 1/20 the rate of a mouse;
      using existing allometric relationships, we calculate that it should be able to
      carry 1 g of its tissue (or a load) for 1 km at 1/40 the cost for a mouse. These
      relationships between energetics and size are so consistent that they have been
      characterized as biological laws. The elephant has massive legs and lumbers along
      awkwardly, suggesting that it might expend more energy to move about than other
      animals. We find, however, that its energetic cost of locomotion is predicted
      remarkably well by the allometric relationships and is the lowest recorded for
      any living land animal.

PMID- 7714453
TI  - Exotic collagen gradients in the byssus of the mussel Mytilus edulis.
AB  - Byssal threads of the common mussel Mytilus edulis contain collagenous molecules
      from which two pepsin-resistant fragments have been isolated and characterized.
      These show a complementary distribution along the length of the thread, such that
      one predominates distally (Col-D) and the other proximally (Col-P). Both
      fragments contain three identical alpha-like chains with molecular masses of 50
      kDa (Col-P) and 60 kDa (Col-D) and have typically collagenous amino acid
      compositions; for example, 35% glycine and almost 20% proline plus 4-trans
      hydroxyproline. Hydroxylysine and 3-hydroxyproline were absent. Col-P sequences
      are also typical of collagen in consisting of tandem repeats of the triplet Gly-X
      Y in which X and Y generally represent any amino acid. When proline occurs, it is
      hydroxylated to 4-trans-hydroxyproline only in the Y position. Seven instances
      where X is glycine have been detected in Col-P. Specific polyclonal anti-Col
      antibodies were used to isolate the precursors of Col-P and Col-D from the mussel
      foot. PreCol-P has a molecular mass of 95 kDa and contains 36% glycine but a
      lower imino acid content (13%). It has a complementary distribution with another
      precursor (preCol-D, 97 kDa) along the length of the foot. The two precursor
      compositions suggest resilin-like and silk-fibroin-like structures, respectively,
      in the noncollagenous domains of preCol-P and preCol-D. Immunogold labelling
      studies indicate that Col-P is associated with the coiled fibers of the inner
      core in the proximal portion of the thread, whereas Col-D is localized to the
      straight fiber bundles of the distal thread as well as to the outer core of the
      proximal thread.

PMID- 7714454
TI  - Effect of beat frequency on the velocity of microtubule sliding in reactivated
      sea urchin sperm flagella under imposed head vibration.
AB  - The heads of demembranated spermatozoa of the sea urchin Tripneustes gratilla,
      reactivated at different concentrations of ATP, were held by suction in the tip
      of a micropipette and vibrated laterally with respect to the head axis. This
      imposed vibration resulted in a stable rhythmic beating of the reactivated
      flagella that was synchronized to the frequency of the micropipette. The
      reactivated flagella, which in the absence of imposed vibration had an average
      beat frequency of 39 Hz at 2 mmol l-1 ATP, showed stable beating synchronized to
      the pipette vibration over a range of 20-70 Hz. Vibration frequencies above 70 Hz
      caused irregular, asymmetrical beating, while those below 20 Hz induced
      instability of the beat plane. At ATP concentrations of 10-100 mumol l-1, the
      range of vibration frequency capable of maintaining stable beating was
      diminished; an increase in ATP concentration above 2 mmol l-1 had no effect on
      the range of stable beating. In flagella reactivated at ATP concentrations above
      100 mumol l-1, the apparent time-averaged sliding velocity of axonemal
      microtubules decreased when the imposed frequency was below the undriven
      flagellar beat frequency, but at higher imposed frequencies it remained constant,
      with the higher frequency being accompanied by a decrease in bend angle. This
      maximal sliding velocity at 2 mmol l-1 ATP was close to the sliding velocity in
      the distal region of live spermatozoa, possibly indicating that it represents an
      inherent limit in the velocity of active sliding.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7714457
TI  - Heart rate variability in coronary artery disease.
AB  - Heart rate variability (HRV) reflects the modulation of cardiac function by
      autonomic and other physiological systems, and its measurement from ambulatory
      electrocardiograph (ECG) recordings is a useful method for both clinical and
      scientific purposes. Heart rate variability can be measured by several linear and
      non-linear methods, and various methods can give different information on neural
      and other physiological influences on the heart. Heart rate variability is
      abnormal in various settings of ischaemic heart disease, and the most important
      current application of HRV analysis in clinical cardiology is its measurement in
      postinfarction patients, in whom abnormal HRV indicates an increased risk of
      cardiac mortality. Future research may expand the clinical utility of HRV
      measurement to other clinical situations.

PMID- 7714455
TI  - Heart mitochondrial properties and aerobic capacity are similarly related in a
      mammal and a reptile.
AB  - The heart mitochondrial properties and the aerobic capacity (VO2max) of the rat
      (Sprague-Dawley breed) and the Cuban iguana (Cyclura nubila) were used to
      evaluate the relationship between the oxidative capacity of the heart and the
      maximum oxygen delivery rate. Both species are active at body temperatures of 37
      39 degrees C, have similar heart mitochondrial volumes [Vmt; 0.43 +/- 0.02 ml
      (S.E.M.) in the rat and 0.48 +/- 0.02 ml in the iguana] and differ less than
      twofold in VO2max (29.2 +/- 1.6 and 16.9 +/- 0.6 ml min-1, respectively). We
      found that Vmt was closely correlated with VO2max in the rat (r2 = 0.77, P <
      0.005) and the iguana (r2 = 0.82; P < 0.001). Furthermore, the inner
      mitochondrial membrane (cristae) area (Sim) per unit VO2max did not differ
      between the rat and the iguana (0.60 +/- 0.02 and 0.71 +/- 0.02 m2 min ml-1 O2,
      respectively). This correspondence of Sim/VO2max indicates that the rat and the
      iguana have the same cardiac oxidative capacity at the maximum oxygen delivery
      rate. These results suggest that, despite the differences between the
      cardiovascular systems of these species, the cardiac cost of delivering oxygen at
      the aerobic capacity is similar in this mammal and this reptile.

PMID- 7714456
TI  - Integrative biology (physiology)--a necessity!

PMID- 7714458
TI  - The role of lipoprotein(a) in the vascular complications of diabetes mellitus.
AB  - Lipoprotein(a) has been identified as an independent risk factor for
      atherosclerotic vascular disease in non-diabetic populations. Because of its
      potential role in the pathogenesis of both microvascular and macrovascular
      complications in diabetes, there have recently been many reports on
      lipoprotein(a) in diabetic populations. Some studies indicate an association
      between elevated lipoprotein(a) and macrovascular disease in non-insulin
      dependent diabetes mellitus (NIDDM), but this link has not been found with
      insulin-dependent diabetes mellitus (IDDM). In IDDM, elevated lipoprotein(a) has
      been found in groups with diabetic nephropathy and retinopathy, raising the
      possibility that it plays a causative role. The relationship between glycaemic
      control and the lipoprotein(a) level has not been fully resolved. Most studies
      have not found any connection in NIDDM, but some found higher lipoprotein(a)
      levels in hyperglycaemic IDDM patients. Potentially, lipoprotein(a) is an
      important factor linking the microvascular and macrovascular complications of
      diabetes.

PMID- 7714459
TI  - Albumin excretion rate and its relation to kidney disease in non-insulin
      dependent diabetes mellitus.
AB  - OBJECTIVE: To estimate the occurrence of increased albumin excretion rate (AER)
      and its significance as a marker of diabetic kidney disease in non-insulin
      dependent diabetic subjects. DESIGN: Population-based, controlled cross-sectional
      study. SETTING: A primary health care centre in the city of Tampere, south-west
      Finland. SUBJECTS: Consecutive, recently diagnosed (n = 150) and long-term (n =
      146) middle-aged non-insulin-dependent diabetic subjects. Matched non-diabetic
      control subjects (n = 150). MAIN OUTCOME MEASURES: Albumin excretion rate,
      fractional AER, microalbuminuria (AER 30-300 mg 24 h-1), clinical nephropathy
      (AER exceeding 300 mg 24 h-1) and kidney biopsy in diabetic subjects with an AER
      exceeding 100 mg 24 h-1. RESULTS: Mean (+/- standard deviation [SD]) 24-h AER was
      increased in recently diagnosed diabetic subjects, 54 (111) mg, and long-term
      diabetic subjects, 134 (479) mg, compared to non-diabetic control subjects, 16
      (19) mg. The fractional AER was 7.5 (18.3) x 10(-6) in recent diabetic subjects,
      53.1 (306.9) x 10(-6) in long-term diabetic subjects and 2.8 (3.7) x 10(-6) in
      non-diabetic control subjects. Microalbuminuria was found in 8% of non-diabetic
      subjects, in 29% of recent and in 27% of long-term diabetic subjects. The
      prevalence of clinical nephropathy was 7% in long-term and 4% in recent diabetic
      subjects, whilst no non-diabetic subject had nephropathy. In 12 of 16 eligible
      kidney biopsies, diabetic glomerulosclerosis was found, in four subjects the
      finding was normal. CONCLUSIONS: The AER is clearly increased in recent non
      insulin-dependent diabetic subjects and further increased in diabetic subjects
      with a mean disease duration of 10 years. An increased AER in non-insulin
      dependent diabetic subjects suggests diabetic kidney disease.

PMID- 7714460
TI  - The role of potassium in postural hypotension: electrolytes and neurohumoral
      factors in elderly hypertensive patients using diuretics.
AB  - OBJECTIVE: To study the association between postural hypotension and (i)
      electrolyte levels and (ii) neurohumoral factors in elderly hypertensive patients
      using diuretics. DESIGN: Cross-sectional study of patients and controls. SETTING:
      The subjects were gathered from senior citizen clubs or they were referred to the
      study by general practitioners. The subjects were examined on a geriatric ward in
      Turku City Hospital. SUBJECTS: Seven subjects with postural hypotension and 13
      controls. MEASUREMENTS: Plasma electrolyte levels and neurohumoral response to
      head-up tilt. RESULTS: There were significantly more hypokalaemic subjects in the
      postural hypotension group (5/7) than in the control group (1/13) (P < 0.01). The
      plasma potassium level was negatively correlated to plasma aldosterone (r = 
      0.57; P < 0.01) and renin activity (r = -0.69; P < 0.001). Subjects with postural
      hypotension had higher levels of noradrenaline, both supine (P < 0.05) and during
      tilt (P < 0.05). There were no significant differences in supine or tilt levels
      of plasma adrenaline, vasopressin, atrial natriuretic peptide, aldosterone and
      renin activity between the groups. CONCLUSION: The results suggest that potassium
      depletion is associated with postural hypotension in elderly hypertensive
      patients using diuretics. However, it is unclear whether there is a causative
      link between potassium depletion and postural hypotension or whether they are
      both caused by some other factor, e.g. volume contraction.

PMID- 7714461
TI  - Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect
      of folic acid.
AB  - OBJECTIVES: Moderate hyperhomocysteinaemia is an independent risk factor for
      cardiovascular disease which may be causal. We investigated whether the
      concentration of plasma homocysteine changes between the acute phase of
      myocardial infarction and follow-up, and whether treatment with oral folic acid
      was effective in lowering homocysteine levels in patients with myocardial
      infarction. DESIGN AND SUBJECTS: Plasma total homocysteine levels 24-36 h
      (baseline) after onset of acute myocardial infarction were compared with the
      levels obtained at 6 weeks' follow-up and with the levels in the controls. In the
      same patients, we studied the effect on plasma homocysteine of 6 weeks' treatment
      with daily oral folic acid doses of 2.5 or 10 mg compared to no treatment.
      RESULTS: At baseline, 12 of 68 patients (18%) had moderate hyperhomocysteinaemia
      (> 17.3 mumol L-1; P < 0.05). Between baseline and follow-up, plasma homocysteine
      levels increased from 13.1 +/- 4.6 to 14.8 +/- 4.8 mumol L-1 (mean +/- SD; P <
      0.001). Treatment with nitroglycerin, streptokinase, beta blockers, or
      acetylsalicylic acid seemed not to have caused this change. Folic acid lowered
      plasma homocysteine in all but two of 33 treated patients with a mean decrease of
      4.4 mumol L-1 (-27%; P < 0.001). There was no difference between the effect of
      2.5 and 10 mg of folic acid. In the untreated group (n = 20), plasma homocysteine
      increased with a mean increase of 0.6 mumol L-1 (+4%; P < 0.05). CONCLUSIONS:
      Plasma homocysteine seems to increase in the post myocardial infarction period,
      the cause of which warrants further study. Folic acid appears to be an effective
      treatment for the reduction of both normal and increased plasma homocysteine
      concentrations in patients with myocardial infarction. This suggests that folic
      acid should be used for intervention when studying the effect of homocysteine
      lowering therapy on the risk on myocardial infarction.

PMID- 7714462
TI  - Motility of small intestine: a case for pattern recognition.

PMID- 7714464
TI  - Gastrointestinal motility disorders in patients with diabetes mellitus.
AB  - Disturbed gastric and small intestinal motility is an often overlooked clinical
      problem. Delayed gastric emptying of liquid and/or solid food in patients with
      type 1 and type 2 diabetes (gastroparesis diabeticorum) occurs in approximately
      50% of the patients. Also, the interdigestive gastric and small intestinal
      motility is often affected. There is only a weak correlation between symptoms and
      objectively measurable motor disturbances. Patients with severe upper
      gastrointestinal symptoms usually have disturbed motility, but most patients with
      impaired motility are asymptomatic. Recent studies have clearly shown that, in
      addition to autonomic neuropathy, acute metabolic derangements are likely to
      contribute to disturbed motility. Elevated glucose levels impair gastric and
      small intestinal motility during fasting and after food intake. Hyperinsulinemia
      per se has effects similar to hyperglycaemia on the stomach and small bowel, and
      may be a mediator of the effects of hyperglycaemia in healthy subjects. The
      impact of insulin on motility in diabetic patients is still unclear. Treatment of
      the gastric motility disorder should include a stabilization of gastric emptying.
      Different therapeutic modes may be useful, e.g. application of prokinetic drugs
      and optimizing the metabolic situation.

PMID- 7714465
TI  - Gastrointestinal motility in obesity.
AB  - Gastrointestinal motility is closely linked to the rate at which nutrients become
      systemically available. Regulation of gastric emptying represents the most
      important brake against delivery of nutrients to the intestine in excess of
      digestive and absorptive capacity. In man, gastric emptying is slowed in
      proportion to the energy density of the meal, which will level out the rate of
      energy delivery to the duodenum. Studies suggest a more rapid gastric emptying in
      obesity, although the opposite has been reported in some experimental settings.
      Moreover, gastric volume is larger in obese individuals and appropriate satiety
      signals are not triggered in response to gastric distension. Postprandial
      intestinal transit time in obesity is similar to that in normal-weight subjects,
      however, despite this fact, intestinal absorption of nutrients is more efficient
      in obesity. Several regulatory mechanisms for gastrointestinal motility, such as
      the autonomous and enteric nervous systems and gastrointestinal regulatory
      peptides, are also of importance for feeding behaviour and metabolism.
      Dysfunction of the autonomous nervous system has been observed, the sensitivity
      to cholecystokinin is decreased in obesity, and plasma concentrations of
      somatostatin and neurotensin are lower than in normal-weight subjects. These
      changes in regulatory mechanisms favour rapid gastrointestinal transit of
      ingested nutrients and promote rapid intestinal absorption in obesity and
      decreased satiety in response to ingested food. It is presently not known whether
      the observed changes in gastrointestinal motility in obesity represent a primary
      feature linked to the pathogenesis of such disease.

PMID- 7714466
TI  - Gastrointestinal motility disorders and bacterial overgrowth.
AB  - Data on the relationship between small intestinal motility, absorption, and
      nutrition are sparse and incomplete. Yet, impaired motility is considered to be a
      plausible cause of bacterial overgrowth, which may have deleterious effects on
      digestion and absorption. This review discusses the scientific validity and
      clinical relevance of the concept that intestinal motor abnormalities are
      responsible for enteric bacterial overgrowth. Disorders associated with
      intestinal dysmotility and bacterial overgrowth, are illuminated, and concurrent
      studies of intestinal motility and microflora are focused on in detail. Moreover,
      practical considerations are given with regard to the clinical management of
      patients with bacterial overgrowth. Available data allow the conclusion to be
      drawn that impaired intestinal motility, as evidenced by attenuated migrating
      motor complex activity, results in bacterial overgrowth. The criteria for an
      intestinal motility disorder likely to result in bacterial overgrowth have been
      determined in patients with late radiation enteropathy, but studies in other
      clinical conditions are needed to establish general guidelines.

PMID- 7714463
TI  - Role of bile in regulation of gut motility.
AB  - Bile empties into the duodenum not only after a meal but also in the
      interdigestive state. In man, interdigestive biliary emptying is related to
      fasting motor activity, the migrating motor complex (MMC), in the stomach and
      small bowel and generally occurs during phase 2 preceding a gastroduodenal phase
      3 activity (activity front). It seems that the main regulatory peptide to
      initiate phase 3 is motilin. During a period with 13 phase 3 activities of MMC,
      18 episodes of gall-bladder emptying and 19 motilin peaks were observed. Such a
      peak of plasma motilin usually took place 25 +/- 11 min after onset of biliary
      emptying. In conclusion, data indicate that motilin is released to the
      circulation by the biliary output and induces phase 3 of MMC. The induced phase 3
      propels bile acids along the gut to promote their absorption in the distal
      intestine. The choleretic action of recycling of bile acids may cause subsequent
      episodes of biliary emptying with motilin release by the action of the
      enterohepatic circulation of bile acids. In such a manner the MMC may be withheld
      as a recycling motility pattern.

PMID- 7714467
TI  - EDTA chelation treatment for peripheral vascular disease.

PMID- 7714468
TI  - von Willebrand factor and atherosclerosis.

PMID- 7714469
TI  - Fate of neglected targets: a chronometric analysis of redundant target effects in
      the bisected brain.
AB  - The authors examined some of the sensorimotor effects of the split-brain
      operation to understand how a "dual mind" can produce unified behavior. They
      report psychophysical evidence of extinction to bilateral simultaneous
      stimulation in callosotomy patient J.W.: Although he could verbally report the
      occurrence of a unilateral left or right visual field target, left field report
      accuracy dropped by 34% when targets occurred bilaterally. Paradoxically, the
      same stimulus conditions produced abnormally robust redundant signal effects on
      simple manual and vocal reaction times, which exceeded predictions that were
      based on probability summation. Neural summation is often inferred from
      redundancy gain of this magnitude. Because this seems less likely after
      callosotomy, the authors suggest a model that is based on response competition
      between the disconnected hemispheres to account for J.W.'s redundant target
      effects. The dissociation between explicit report and motor performance is
      discussed.

PMID- 7714470
TI  - Contribution of listeners' approaching motion to auditory distance perception.
AB  - Of the several sources of acoustic information for distance perception, those
      arising from motion of the listener or sound source have received little
      attention. This motion-related information (recently called acoustic tau) is
      described, and experiments evaluating its utilization are presented. Accuracy and
      consistency at walking to the locations of briefly presented sounds were better
      when people listened while walking than while standing still. Manipulations of
      the sound to simulate shorter or longer target distances produced appropriate
      undershooting but not overshooting. The results indicate that people use motion
      related acoustic information about distance to guide their locomotor actions,
      although they do not take full advantage of this information.

PMID- 7714471
TI  - Classification of color dimensions in multiple contexts.
AB  - Hue, saturation, and brightness were tested in pairs, with one dimension creating
      a classification context and the other serving as the basis of a set of speeded
      classification tasks. In Experiment 1, performance suffered when the context
      setting dimension varied within a response category (intraclass context) and
      benefited when this variation occurred between response categories (redundant
      context). In Experiment 2, participants showed no interference from irrelevant
      variation in tasks that combined intraclass context with redundant context.
      Experiment 3 opened the interpretative window by varying 5 levels of intraclass
      context factorially with 5 levels of redundant context. The dimensions were found
      to differ in hardness--the degree of resistance to intraclass context across
      levels--with hue showing the greatest resistance and brightness the least.
      Hardness may reflect the efficacy of a dimension for distinguishing real-world
      categories.

PMID- 7714472
TI  - Repetition blindness: perception or memory failure?
AB  - Repetition blindness (RB) is the failure to report a repeated item when reporting
      all of the elements from a rapidly displayed sequence of visually presented
      items. N. Kanwisher (1987) has characterized RB as a perceptual problem.
      Experiments 1 and 4 manipulated the order of report of the repeated items.
      Experiments 2-4 employed tasks other than full report that should still have
      shown RB according to a perceptual hypothesis, but none was found. In Experiment
      5, RB was found when one of the repetitions was spoken and the other was
      presented visually; this RB could be localized to retrieval processes. RB appears
      to reflect processes and strategies peculiar to full report from rapid displays
      rather than any fundamental perceptual limitation and might be the same as the
      Ranschburg effect found in immediate recall tasks.

PMID- 7714474
TI  - Discrimination of coherent motion when local motion varies in speed and
      direction.
AB  - Random-dot cinematograms (RDCs) consist of multiple local motion signals that can
      vary in direction and speed. These local motion signals can result in coherent
      motion: the percept of an overall direction and speed of motion in an RDC.
      Thresholds were obtained for discriminating differences in the strength of
      coherent motion. Observers were found to easily discriminate the strength of
      coherent motion on the basis of the elements' direction or speed under optimal
      conditions. However, a nonreciprocal relation was evident when this
      discrimination was performed under nonoptimal conditions. Discrimination of
      coherent motion that was based on the elements' direction was unaffected, but
      discrimination that was based on speed was impaired. Results indicate that humans
      are sensitive to small differences in coherent motion strength and suggest that
      the visual system processes direction and speed information nonreciprocally.

PMID- 7714473
TI  - Tests of attentional flexibility in listening to polyrhythmic patterns.
AB  - Four experiments examined attentional flexibility in listening to polyrhythmic
      patterns. Musically trained and untrained listeners detected changes in timing of
      1 tone (the lower tone) in a 3:2 polyrhythm in which high and low tones varied in
      frequency separation. Experiment 1 encouraged integrative attending; all
      listeners performed significantly poorer in conditions with wide as opposed to
      narrow frequency separations. Experiment 2, which encouraged selective attending
      to low tones, reversed these results: Performance was poorer in the narrow
      frequency conditions. In neither experiment did skill interact with frequency
      separation. Experiments 3 and 4 extended these findings to moderate frequency
      separations. Over all experiments, musically trained listeners exhibited an
      enhanced ability to detect timing variations, but not flexibility of perceptual
      organization as it applies to detection of timing changes. Instead, pattern
      structure (e.g., frequency and time relation) decisively influenced perception
      for both levels of skill.

PMID- 7714475
TI  - The psychological reality of the body schema: a test with normal participants.
AB  - Neuropsychological dissociations suggest the existence of a body schema, a
      representation of the spatial relations among body parts, not used for other
      spatial stimuli. Four experiments verify the psychological reality of the body
      schema in normal participants. In Experiments 1 and 2, proprioceptive information
      concerning one's own body position influences visual perception of others' body
      positions. Contrary to expectations, facilitation is observed rather than
      interference in the dual-performance task. Experiment 3 eliminates the
      possibility that the effect is due to a particular mnemonic strategy. In
      Experiment 4, this effect is shown to be specific to the perception of bodies, as
      opposed to other complex 3-dimensional forms.

PMID- 7714476
TI  - Lexical and prelexical influences on word segmentation: evidence from priming.
AB  - The authors examined the interaction of acoustic and lexical information in
      lexical access and segmentation. The cross-modal lexical priming technique was
      used to determine which word meanings listeners access at the offsets of oronyms
      (e.g., tulips or two lips) presented in connected speech. In Experiment 1,
      participants showed priming by the meaning of tulips when presented with two
      lips. In Experiment 2, priming by the meaning of the 2nd word was found in such
      sequences (e.g., lips in two lips). Finally, Experiment 3 demonstrated that
      listeners do not show priming by lips when it is pronounced as part of tulips.
      The results of these experiments show that listeners sometimes access words other
      than those intended by speakers and may simultaneously access words associated
      with several parses of ambiguous sequences. Furthermore, the results suggest that
      acoustic marking of word onsets places constraints on the success of lexical
      access. To account for these results, the authors propose a new model of lexical
      access and segmentation.

PMID- 7714477
TI  - Manipulating symmetry in the coordination dynamics of human movement.
AB  - J. A. S. Kelso and J. J. Jeka (1992) demonstrated that symmetry is a useful
      conceptual tool to distinguish the coordination between components with similar
      versus different anatomical properties. The present experiments studied human arm
      leg patterns to test whether their coordinative asymmetry was changed by
      manipulating the inertial properties of a single limb. The results showed that
      (a) consistent with model predictions, adding weight to the arm or the leg
      minimized or enhanced coordinative asymmetry, respectively and (b) the response
      to a perturbation slowed as movement frequency increased but in a fashion that
      reflected the underlying coordinative asymmetry. The observed coordinative
      effects suggest the influence of neural phase relationships and emphasize that
      symmetry plays an important role in understanding coordination in systems in
      which control cannot be traced unequivocally to a single end-effector or a
      neurophysiological substrate.

PMID- 7714478
TI  - Abstract visual-form representations in the left cerebral hemisphere.
AB  - Visual-form systems in the cerebral hemispheres were examined in 3 experiments.
      After learning new types of visual forms, participants rapidly classified
      previously unseen prototypes of the newly learned types more efficiently when the
      forms were presented directly to the left hemisphere (in the right visual field)
      than when the forms were presented directly to the right hemisphere (in the left
      visual field). Neither previously seen nor previously unseen distortions of the
      prototypes were classified more efficiently when presented directly to the left
      hemisphere than when presented directly to the right hemisphere. Results indicate
      that an abstract visual-form system operates effectively in the left hemisphere
      and stores information that remains relatively invariant across the specific
      instances of a type of form to distinguish different types. Furthermore, this
      system functions relatively independently of another system that operates
      effectively in the right hemisphere and that stores details to distinguish
      specific instances of a type of form.

PMID- 7714479
TI  - Shifting and focusing auditory spatial attention.
AB  - Auditory spatial attention was investigated by manipulating spatial and temporal
      relations between an auditory spatial cue and an auditory target. The principal
      findings were that performance improved as time available to shift attention to a
      cued spatial position increased, accurate spatial cues facilitated performance
      more than inaccurate cues, performance was virtually identical for shifts of
      attention ranging from 0 degrees and 180 degrees, and performance declined as the
      distance of an unexpected target from a cued spatial location increased. The
      experiments provided evidence that auditory attention may be allocated to a
      specific location in response to an auditory spatial cue and that the time
      required to shift attention does not appear to depend on the distance of the
      shift. Furthermore, the findings suggest that the spatial distribution of
      auditory attention may be described most accurately by a gradient model in which
      attentional resources decline gradually with distance from a focal point.

PMID- 7714480
TI  - The cerebral hemispheres and neural network simulations: design considerations.
AB  - The conclusions concerning hemispheric specializations based on neural network
      simulations, which were previously reported by Kosslyn, Chabris, Marsolek, and
      Koenig (1992), are shown not to be valid. Differences in network performance on
      tasks said to be "categorical" and "coordinate spatial" in nature were due to
      imbalances in the input stimuli and cannot, in principle, be related to
      differences in performance on such tasks in human subjects. The use of truth
      tables and correlation coefficients in the design of neural networks is
      discussed.

PMID- 7714481
TI  - On computational evidence for different types of spatial relations encoding:
      reply to Cook et al. (1995).
AB  - Computational models in psychology play an increasingly important role in
      characterizing theoretical distinctions, understanding empirical results, and
      formulating new predictions. However, the proper use of models is subject to
      debate and interpretation, as Cook, Fruh, and Landis (1995) have demonstrated in
      a critique of neural network simulations reported by Kosslyn, Chabris, Marsolek,
      and Koenig (1992). These simulation results supported a distinction between two
      types of spatial relations encoding. Cook et al. argue that Kosslyn et al.'s
      models did not process "spatial" representations and that input-output
      correlations rather than properties of spatial relations encoding processes
      explain the performance of the models. This article provides conceptual and
      analytic rebuttals of those criticisms.

PMID- 7714482
TI  - Models of interlimb coordination--equilibria, local analyses, and spectral
      patterning: comment on Fuchs and Kelso (1994).
AB  - This article is a comment on A. Fuchs and J. A. S. Kelso's (1994) theoretical
      note on models of interlimb coordination. The generality of the order parameter
      equation derived by H. Haken, J. A. S. Kelso, and H. Bunz (HKB; 1985) for
      correlated limb movements is underscored through the correct and nonintuitive
      predictions it makes about steady state behavior. Local and global dynamical
      models are contrasted, and experimental situations in which local models are
      pragmatic alternatives to global models, like the HKB equation, are described.
      Questions are raised about the basis for interpreting detuning in HKB as a simple
      frequency difference and about the ability of the system of coupled nonlinear
      oscillators proposed by A. Fuchs and J. A. S. Kelso (1994) to model fully the
      experimental findings on the spectrum of relative phase.

PMID- 7714483
TI  - A rapid and sensitive method of identification of HTLV-II subtypes.
AB  - There are 2 subtypes of human T-cell lymphoma/leukemia virus type II (HTLV-II), A
      and B. HTLV-II is increasingly associated with rare forms of lymphocytic
      neoplasia and a neurodegenerative disorder, characterized by hyperspasticity and
      ataxia. We have used PCR to amplify, clone and sequence 140 bp of the pol gene
      from many isolates of HTLV-IIA and HTLV-IIB from around the world. Analysis of
      these and other published sequence established that all HTLV-IIA sequences
      contained a unique Hinf I site and all HTLV-IIB sequences a unique Mse I site. A
      rapid and specific oligomer restriction (OR) assay was developed utilizing the
      primer pair SK110/SK111 and subsequent digestion with these enzymes. Concordance
      between sequenced and OR-based subtyping of DNA amplified by PCR was absolute
      among 22 HTLV-II isolates tested. Further OR or sequence analyses on an
      additional 30 other isolates indicated that the majority of North American non
      indian HTLV-II isolates were subtype A, while all Paleo-Amerindian samples,
      including those from the Seminole of Florida; the Guaymi from Panama; and the
      Toba, Chorote, Wichi, and Chulupe of Argentina, belonged to subtype B. The
      SK110/SK111 PCR-OR format should facilitate molecular epidemiology studies of
      HTLV-II infection and allow for subtype stratification in assessing the
      sensitivity and specificity of HTLV detection formats and HTLV-II disease
      association.

PMID- 7714484
TI  - GACPAT HIV 1 + 2: a simple, inexpensive assay to screen for, and discriminate
      between, anti-HIV 1 and anti-HIV 2.
AB  - A simple and cheap assay suitable for screening for anti-HIV 1 and anti-HIV 2 and
      discriminating between them was evaluated. In it specimens are incubated in U
      bottomed microplate wells coated with anti-human IgG for 30 min at room
      temperature. After washing, 100 microliters of a 1 in 50 dilution of HIV 1-coated
      gelatin particles (Serodia-HIV 1/2, Fujirebio) are added. Settling patterns are
      read on the second day: A positive reaction is indicated by adherence of the
      particles and a negative by a button. The HIV 1 particles are then washed away
      and HIV 2 particles added. Anti-HIV 2 reaction patterns are read on the third
      day. To assess the performance of the modified "GACPAT HIV 1 + 2" assay a panel
      of 1,621 serum/plasma specimens was used. It comprised validated anti-HIV 1
      positive (n = 220), anti-HIV 2 positive (n = 214), dual anti-HIV 1/anti-HIV 2
      positive (n = 11), and anti-HIV negative (n = 1,176) serum/plasma specimens. All
      434 specimens that contained anti-HIV 1 or anti-HIV 2 reacted positively with the
      homologous particles. The 11 dually positive specimens reacted positively with
      both HIV 1 and HIV 2 particles. Five (2.3%) anti-HIV 1 and five (2.3%) anti-HIV 2
      positive specimens gave positive reactions with both particle types, but none of
      the five cross-reactive anti-HIV 2 specimens were dually reactive when the order
      of particle addition was reversed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714485
TI  - Controlled study of human herpesvirus 6 detection in acquired immunodeficiency
      syndrome-associated non-Hodgkin's lymphoma. The French Study Group for HIV
      Associated Tumors.
AB  - Human herpesvirus 6 (HHV-6) is a recently identified lymphotropic herpesvirus,
      which has been isolated from patients with acquired immunodeficiency syndrome
      (AIDS) or lymphoproliferative diseases. Two variants A and B of HHV-6 have been
      described, variant B being more common in children with exanthema subitum. HHV-6
      infection was studied in cases of AIDS-associated non-Hodgkin's lymphoma (NHL),
      and in three control populations in order to evaluate the possible etiological
      role of HHV-6 in this lymphoproliferative disease. Tumor specimens from various
      organs were obtained from 27 patients with AIDS-associated NHL and 20 human
      immunodeficiency virus (HIV)-seronegative patients with NHL. Lymph node specimens
      were obtained from four HIV-seropositive and nine HIV-seronegative patients with
      lymph node follicular hyperplasia. A specific polymerase chain reaction (PCR) was
      used to detect HHV-6 DNA. Subsequently HHV-6 variant was identified by using
      variant-specific PCR. Human cytomegalovirus (CMV) infection was detected in
      parallel by means of specific PCR. HHV-6 DNA was detected in 12 of 27 tumor
      tissues (44%), including 8 of 15 lymph node specimens (53%) from patients with
      AIDS-associated NHL. The corresponding values in HIV-seronegative patients with
      NHL were 35% (7/20) and 36% (5/14), respectively. Lymph node specimens were
      positive for HHV-6 in two of four (50%) HIV-seropositive and five of nine (55%)
      HIV-seronegative patients with follicular hyperplasia. Variant A was detected in
      two cases of AIDS-associated NHL, variant B in one case, and both variants in six
      cases. The distribution of HHV-6 variants exhibited a similar pattern in the
      three control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714486
TI  - Detection of seminal antibodies to human immunodeficiency virus in vaginal
      secretions after sexual intercourse: possible means of preventing the risk of
      human immunodeficiency virus transmission in a rape victim.
AB  - Detection of semen anti-human immunodeficiency virus (HIV) antibodies within the
      cervicovaginal secretions from a non-HIV-infected woman who has had a recent
      sexual intercourse with an HIV-infected man is theoretically possible since the
      seminal fluid from all HIV-infected men contains a high titer of IgG antibodies
      to HIV. We report the case of an HIV-seronegative African woman whose cervico
      vaginal secretions contained IgG antibodies to HIV, including antibodies to HIV
      env-encoded glycoproteins. This woman had also detectable prostatic specific
      antigens and acid phosphatase in her cervico-vaginal secretions, establishing the
      persistence of semen. In order to confirm whether anti-HIV antibodies in seminal
      fluid could be detected in vitro when mixed with cervico-vaginal secretions, 10(
      1) to 10(-6) 10-fold dilutions of seminal fluid from HIV-1-seropositive donors
      were realized with a pool of HIV-negative cervico-vaginal secretions as diluent.
      Six commercial enzyme immunoassays or rapid tests were compared for semen anti
      HIV detection in the secretions. At a 10(-1) dilution of the mixture, all assays
      were markedly positive for all tested semens and the greatest dilutions of
      seminal fluid showing positivity ranged from 10(-3) to 10(-5). The IgG
      immunocapture assay appeared to be the most sensitive test. The rapid tests
      permitted the detection of semen IgG antibodies to HIV at dilutions ranging from
      10(-1) to 10(-3) suggesting their potential value in emergency situations.

PMID- 7714487
TI  - Typing of human group A rotavirus with alkaline phosphatase-labeled
      oligonucleotide probes or a monoclonal enzyme immunoassay in unfrozen stools of
      children with diarrhea in Bangkok.
AB  - In developed countries, serotypes (or G types) have been identified in > 70% of
      group A rotavirus using monoclonal enzyme immunoassays (MEIAs); however, these
      assays have identified < 50% of rotavirus G types from developing countries
      presumably because the VP7 antigens were damaged by freezing and thawing during
      transportation of specimens. The VP7 (G) serotypes of rotavirus in unfrozen stool
      collected from children with acute diarrhea in Bangkok were determined using MEIA
      and compared to hybridization with alkaline phosphatase-labeled oligonucleotide
      probes. Reverse transcription of dsRNA coding for VP7 followed by polymerase
      chain reaction amplification of cDNA was used as an additional step prior to
      hybridization for 98 specimens that did not hybridize with the oligonucleotide
      probes. Of 251 rotavirus specimens, 208 (83%; 99% Cl = 76-89%) hybridized with G
      type specific oligonucleotides compared to 146 (58%; 99% Cl = 50-66%) that were
      typeable by MEIA. Forty-five (82%) of 55 stools containing G type 1, 80 of 84
      (95%) containing G type 2, 0 of 3 containing G type 3, and 2 of 4 (50%)
      containing G type 4 as identified by MEIA hybridized with G type specific
      oligonucleotides. Differences in nucleotide sequences coding for VP7, in addition
      to destruction of the VP7 antigen by freezing and thawing of the specimen, may
      explain why not all rotavirus hybridized with G type specific probes.

PMID- 7714488
TI  - Symptomatic mumps virus reinfections.
AB  - Although natural mumps virus infection is believed to induce lifelong immunity,
      our laboratory was confronted with 82 patients who developed mumps-evoking
      lesions but exhibited serological evidence of a booster immune response, namely a
      rise or a high titer of virus-specific IgG, without IgM. In order to provide
      arguments favoring the existence of recurrent mumps attacks, the age,
      symptomatology, and humoral response of these patients (group 1) were compared to
      that of 82 randomly selected true primary infected patients (group 2), 10
      parainfluenza virus-infected patients (group 3), and 20 noninfected mumps-immune
      subjects (group 4). Enzyme-linked immunosorbent assay (ELISA) procedures with
      different viral antigenic preparations were used for determination of specific
      IgM, IgA, IgG, IgG subclasses, and IgG avidity. The patients of group 1, older
      than those of group 2 (28 vs. 10 years, P < 0.0001), presented a significantly
      less severe and less typical symptomatology. Against the whole virus they
      exhibited IgG of higher avidity (P < 0.001), a lower prevalence and titer of IgA
      (10 vs. 68%, P < 0.0001 and 278 vs. 5,009, P < 0.001, respectively). Values
      obtained for IgG 1, 2, and 3 were significantly different between the two groups.
      Prevalence and absorbance of nucleocapsid-directed IgG 3 were significantly lower
      in group 1 (27 vs. 46%, P < 0.01 and 0.444 vs. 0.869, P < 0.01, respectively). A
      significant discrepancy also allowed patients from group 1 to be distinguished
      from those of groups 3 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714489
TI  - Unbiased usage of T-cell receptor beta variable region genes in peripheral blood
      cells of hepatitis C patients: no correlation with superantigen effect.
AB  - Hepatitis C virus (HCV) infection frequently causes chronic hepatitis and lack of
      virus clearance in these patients. In addition, many patients infected by HCV
      also present with hypergammaglobulinemia in the early stage of chronic infection.
      These observations raise a possible viral superantigen effect induced by HCV,
      because viral superantigen found in human immunodeficiency virus (HIV) or in
      replication of defective murine leukemia virus (MuLV) is associated with T-cell
      dysfunction and polyclonal activation of B cells. The possibility was
      investigated of whether HCV encodes any superantigen by analyzing the usage of T
      cell receptor (TCR) from the peripheral blood lymphocytes (PBL) of patients with
      chronic hepatitis C. Two groups, one with hypergammaglobulinemia and the other
      without hypergammaglobulinemia, were studied for the usage of TCR beta chain by
      reverse transcription-polymerase chain reaction (RT-PCR) analysis. It was found
      that all genes of V beta variable chain were used in the PBL of these patients.
      Furthermore, there was no significant difference of the TCR expression pattern
      between these two groups, nor a complete deletion of a particular T-cell subset
      in either group. These results do not provide evidence for HCV superantigen, but
      indicate that the TCR usage in the patients was neither defective nor biased.

PMID- 7714490
TI  - Effects of ribavirin on intrahepatic and extrahepatic expression of hepatitis C
      virus in interferon nonresponsive patients.
AB  - Response to ribavirin therapy (1,000-1,200 mg/day for 6 months) was evaluated in
      nine patients with chronic hepatitis C virus (HCV) infections who had previously
      failed to respond to a 6-month course of alpha-interferon. All had chronic active
      hepatitis with elevated serum aminotransferase activities (mean +/- SD = 138 +/-
      66IU/I). During ribavirin therapy, three showed a complete response (normalized
      serum aminotransferase), although in one patient this returned to the
      pretreatment level 2 months after treatment was stopped. Three others showed a
      partial response (serum aminotransferase reduction by > or = 50%) and the
      remainder showed no response. There were no consistent changes in HCV-RNA
      (positive strand) in serum, liver, or peripheral blood mononuclear cells during
      therapy, but two patients lost HCV-RNA from serum and three of five patients with
      negative strand HCV-RNA in their livers lost this putative replicative form of
      the virus. The findings suggest that ribavirin may exert its effects by
      suppressing viral replication rather than by eradicating the virus, at least in
      this group of patients, and that the drug may have some benefit in selected cases
      of chronic hepatitis C that are resistant to interferon. However, peripheral
      blood mononuclear cells represent a major extrahepatic reservoir of HCV and the
      present regimen of ribavirin therapy did not significantly affect this situation.
      More prolonged therapy may be required to eradicate the virus from this large
      pool of cells with the potential to continually reinfect the liver.

PMID- 7714491
TI  - Clinical recurrence of hepatitis A following liver transplantation for acute
      liver failure.
AB  - This paper documents clinically significant recurrence of hepatitis A virus (HAV)
      infection in a 63-year-old man transplanted for HAV-related acute liver failure.
      HAV RNA was documented in the explant and, following early clearance from the
      blood and graft, was again detected in post-operative biopsies at the time of an
      acute hepatic illness. Although the clinical and biochemical abnormalities
      resolved completely, the patient had a second episode of graft dysfunction 6
      months later and investigations revealed hepatitis C virus (HCV)-related chronic
      active hepatitis consistent with acquired HCV infection at the time of
      transplantation. The possible interaction with hepatitis A may have delayed the
      appearance of hepatitis C. Administration of HAV immunoglobulin at the time of
      transplantation should be considered in all cases of HAV-related fulminant
      hepatic failure.

PMID- 7714492
TI  - Enteric prevalence of adenovirus in human immunodeficiency virus seropositive
      patients.
AB  - To evaluate the prevalence of adenovirus strains in human immunodeficiency virus
      (HIV)-positive patients and to investigate their possible role in the onset of
      diarrhea, a total of 103 stools from HIV-seropositive patients at various stages
      of infection and 200 stools from sex and age cross-matched control subjects were
      examined. Adenovirus prevalence was measured by ELISA as well as conventional and
      rapid cell culture techniques. Results were compared between patients suffering
      from diarrhea and those without diarrhea. Adenovirus prevalence was statistically
      greater in HIV-seropositive cases than controls (8.7%, 2.5%, respectively). No
      significant difference was found between HIV-positive patients with diarrhea and
      those without gastrointestinal complications (P > 0.05). However, a significant
      difference in adenovirus prevalence was found between HIV-positive patients with
      diarrhea and control subjects with diarrhea (P = 0.02). Although viral prevalence
      varied with the different stages of HIV infection, differences were not
      statistically significant. In conclusion, although current opinion considers
      adenoviruses to be no more than opportunistic pathogens, the results of this
      large-scale study do not exclude a potential reactivation of latent adenovirus in
      HIV infection and suggest that further effort should be directed to elucidating
      such a mechanism if it exists as well as investigating the specific role of
      certain adenovirus serotypes in provoking diarrhea during later stages of HIV
      infection.

PMID- 7714493
TI  - Epidemiology of Norwalk virus during an outbreak of acute gastroenteritis aboard
      a US aircraft carrier.
AB  - A large outbreak of acute gastroenteritis occurred over a 5-week period aboard an
      aircraft carrier. The estimated cumulative attack rate was 13% among the 4,500
      man crew. Eight percent of the crew sought medical attention, nearly all of whom
      missed 1 day or more of work. The risk of developing illness was 2 to 3 times
      greater for individuals living in more crowded sleeping quarters (> 50 persons
      per compartment). Occurrence of gastroenteritis was associated with a fourfold or
      more rise in Norwalk virus antibody levels, as measured by an enzyme-linked
      immunoassay utilizing a baculovirus expressed recombinant antigen. In addition,
      27 nm Norwalk virus-like particles were visualized in two of six stools examined
      by immune electron microscopy. The presence of a low (< 1:50) or a high (> or =
      1:6,400) pre-illness antibody level was associated with a lower incidence of
      illness. This investigation indicates that Norwalk virus can adversely impact
      operations of a military vessel and that crowding is a major risk factor in
      transmission.

PMID- 7714494
TI  - Evidence for lytic infection by Epstein-Barr virus in mucosal lymphocytes instead
      of nasopharyngeal epithelial cells in normal individuals.
AB  - Normal nasopharyngeal tissues from 23 individuals who died of causes unrelated to
      the upper respiratory system and had no evidence of Epstein-Barr virus (EBV)
      related diseases were studied using in situ hybridisation (ISH) and
      immunohistochemistry for the detection of EBV RNA and expression of EBV proteins,
      respectively. ISH using 35S-labelled riboprobe for EBV EBER RNA showed occasional
      to a few EBER+ lymphocytes in the stroma of nasopharyngeal mucosa in 14/16 cases
      with available paraffin-embedded tissues. In addition, very rare intraepithelial
      EBER+ lymphocytes were also detected in 3/16 cases. However, in none of these
      cases was EBER detected in the epithelial cells. Similar results were obtained
      using a nonradioactive ISH method for EBER (Dako). In 3/23 cases, immunostaining
      using monoclonal antibodies for EBV proteins on cryostat sections showed
      occasional cells in the stroma expressing EBV nuclear antigen 2 (EBNA2), latent
      membrane protein-1 (LMP), and switch protein encoded by BZLF1 gene (ZEBRA) in two
      cases and only very rare LMP+ and ZEBRA+ cells in one other case. Double
      immunostaining combining alkaline phosphatase anti-alkaline phosphatase (APAAP)
      for CD markers and indirect immunofluorescence for LMP showed that the LMP+ cells
      were either CD19+ or less frequently CD3+, but none were CD68+. These results
      show that both B and T lymphocytes harbouring EBV can be found in the normal
      nasopharyngeal tissues. Interestingly, EBV proteins associated with lytic viral
      replication--diffuse early antigen (EA-D), viral capsid antigen (VCA), or
      membrane antigen (MA)--were also detected in rare cells in the stroma in one
      case, and in another case only one MA+ cell was detected.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7714495
TI  - Infectious virus titer, replicative and syncytium-inducing capacity of human
      immunodeficiency virus type 1.
AB  - The relationship was investigated between a viral infectious titer in peripheral
      blood mononuclear cells (PBMC) and plasma on the replicative and syncytium
      inducing capacity of human immunodeficiency virus type 1 (HIV-1) isolates. The
      replicative capacity was defined as the minimum time required for p24 antigen to
      become positive in PBMCs or plasma of HIV-1 infected individuals, cocultured with
      PBMCs of healthy donors. Syncytium induction was determined by the MT-2 cell
      assay and defined as the presence of giant multinucleated cells. The replicative
      capacity of HIV-1 in PBMCs of healthy donors correlated with the infectious viral
      titer in PBMCs, but not in the plasma of HIV-1 positive patients. Syncytia
      formation in MT-2 cells was not related to the infectious viral titer in PBMCs or
      plasma of HIV-1 positive patients. These findings suggest that syncytium
      formation, not replicative capacity, is an intrinsic HIV-1 phenotype.

PMID- 7714496
TI  - Hepadna virus integration generates virus-cell cotranscripts carrying 3'
      truncated X genes in human and woodchuck liver tumors.
AB  - Integration of the human and woodchuck hepatitis B viruses (HBV and WHV) in host
      chromosomes has been implicated in the development of hepatocellular carcinoma by
      different cis- and trans-acting mechanisms. The structure and coding capacity of
      abundant HBV and WHV transcripts of abnormal sizes produced from integrated viral
      sequences in one human and two woodchuck liver tumors were examined. Analysis of
      cDNA clones revealed in all cases hybrid virus-cell transcripts containing
      sequences of the viral surface gene, the viral enhancer, and different truncated
      versions of the viral X transactivator. Cotranscribed cellular sequences showing
      no significant coding function provided the signals for transcription
      termination. In two transcripts, the HBX and WHX genes truncated at carboxy
      terminal positions conserved transcriptional trans-acting capacity in transient
      transfection assays. These results lend support to the hypothesis that the
      integrated hepadnavirus X transactivator might participate in the development of
      woodchuck as well as human liver tumors by a common trans-acting mechanism.

PMID- 7714497
TI  - Increased number of single-LTR HIV-1 DNA junctions correlates with HIV-1 antigen
      expression and CD4+ cell decline in vivo.
AB  - Human immunodeficiency type 1 (HIV-1) DNA in peripheral blood cells of HIV-1
      infected individuals may be present as integrated and/or unintegrated DNA.
      Several reports have indicated that a major proportion of HIV-1 DNA in the
      asymptomatic phase is linear, full-length, and unintegrated and in the
      symptomatic phase either circular unintegrated or integrated in the host genome.
      We developed a quantitative polymerase chain reaction (PCR) technique to detect
      single-LTR HIV-1 DNA junctions, reflecting the presence of unintegrated single
      LTR circles. In vitro infection of a CD4+ T-cell line resulted first in the
      increase of single-LTR junctions followed by syncytium formation and a rise of
      p24 antigen production. The number of single-LTR HIV-1 DNA junctions was further
      studied in two acutely infected individuals and in 21 long-term infected
      individuals. The number of single-LTR junctions was significantly correlated with
      CD4+ cell decline, p24 antigen expression, and total HIV-1 DNA content of
      peripheral blood mononuclear cells (PBMC). Single-LTR HIV-1 DNA junctions were
      absent from PBMC containing other forms of HIV-1 DNA in four of nine non/slow
      progressors relative to 2 of 12 rapid progressors/AIDS patients. We conclude from
      our data that quantitative detection of single-LTR HIV-1 DNA junctions can be
      used as an early DNA marker of the transition from clinical latency to active
      replication in the peripheral blood.

PMID- 7714498
TI  - Expression of the Epstein-Barr virus DNA polymerase in Escherichia coli for use
      as antigen for the diagnosis of nasopharyngeal carcinoma.
AB  - Epstein-Barr virus (EBV) encoded DNA polymerase (POL) was cloned and over
      expressed in Escherichia coli. Western blot analysis confirmed the presence of
      antibody to this POL protein in sera from nasopharyngeal carcinoma (NPC)
      patients. By Western blot analysis, moderate to high concentration of IgG POL
      specific antibodies were present in 43 of 48 NPC sera and only 4 of 48 healthy,
      seropositive controls. The POL-specific IgG antibodies appear as early as stage I
      of NPC, suggesting that the recombinant POL protein can be a useful diagnostic
      marker for early diagnosis of the disease. It was also found that human sera
      containing high titer of cytomegalovirus (CMV) antibodies or herpes simplex virus
      type 1 (HSV-1) antibodies did not cross-react with the recombinant EBV POL,
      despite the homology shared by DNA polymerase proteins of these viruses.

PMID- 7714499
TI  - Visual evoked potentials in early Alzheimer's dementia: an exploratory study.
AB  - Topographical maps of visual evoked potentials (VEPs) were recorded from 10
      possible Alzheimer's disease (AD) patients and 10 control subjects. The purpose
      of the study was to determine if the two types of VEPs could function as a
      diagnostic screening for AD. Results of the statistical analysis did not reveal
      any latency differences between VEPs for the components elicited by either the
      pattern shift visual evoked potential (PSVEP)--or flash visual evoked potential
      (FVEP)--elicited components for AD patients compared with the control subjects;
      however, the information provided insight into results that are frequently lost
      with conventional evoked potential data. Statistically significant differences in
      amplitude were found between the P1 and the N2 of the PSVEP at 124, 126, and 130
      ms, and at 116 ms for the FVEP.

PMID- 7714500
TI  - When infants wail: frustration and gender as variables in distress disclosure.
AB  - Gender and differences in self-disclosure following a frustrating event were
      investigated. The Emotional Self-Disclosure Scale assessed the extent to which
      100 male college students and 100 female college students were willing to
      disclose their emotions. The frustrating stimulus presented was a tape of an
      infant crying, played at 85 dB for 10 min. Men exposed to the noxious stimulus
      were less willing to disclose than men who were not. All of the men were less
      willing than the women to disclose in either condition. Women in the two
      conditions showed no differences in disclosure. These findings are interpreted
      with respect to how disclosure is affected by the immediate environment and with
      respect to male-female differences.

PMID- 7714501
TI  - Neuroticism, mood, and retrieval of negative personal memories.
AB  - Most studies of the effects of neuroticism on memory investigate the recall of
      self-related material learned during the course of the experimental session. The
      present study was designed to examine the effects of neuroticism on more complex
      personal events in real life. High levels of neuroticism were associated with a
      tendency toward fewer happy thoughts and memories. The results also suggest that
      neuroticism increased retrieval of negative personal memories independent of
      depressed mood. These findings are discussed in relation to cognitive
      vulnerability to depression.

PMID- 7714502
TI  - Foot-preference behavior: a developmental perspective.
AB  - The developmental course of foot-preference behavior was examined in participants
      spanning early childhood to young adulthood. Results indicated significant age
      group differences, with no effect for gender. Evidence suggests that footedness
      adheres to some variant developmental features characterized primarily by a
      significant shift toward greater right-footedness between 8 and 11 years, after
      which preferences remain relatively stable. Complementing this shift is a
      substantial decrease in mixed-footedness across the same time line. Of the
      existing models of hemispheric specialization, Annett's (1978, 1985) right-shift
      hypothesis, which considers cultural and environmental effects, provides a
      partial explanation for the findings. Hand-preference data were also collected
      and are contrasted with foot-preference data.

PMID- 7714503
TI  - Touch sensitivity through latex examination gloves.
AB  - Two studies were conducted to empirically evaluate individuals' touch sensitivity
      while wearing latex medical-examination gloves. In Experiment 1, three
      sensitivity threshold measures (two-point, von Frey, and thumb-index finger
      opposition) were used in three conditions--no glove, best-fitting glove, and ill
      fitting glove. No effect of glove condition was found for the two-point measure,
      but significant effects were found for the von Frey and finger-opposition
      measures. In Experiment 2, participants attempted to sense the presence or
      absence of monofilament fibers of different diameters. Glove condition (no glove,
      best-fitting, and ill-fitting) and touch strategy (active vs. passive) were
      manipulated for each participant. Although there was no overall effect for glove
      condition, active touch proved consistently superior to passive touch.

PMID- 7714505
TI  - Evidence for frequency-dependent and frequency-independent components in
      increasing- and decreasing-loudness aftereffects.
AB  - Listening to a decreasingly intense tone leads to increasing loudness in a
      subsequent steady tone. Conversely, listening to an increasingly intense tone
      leads to decreasing loudness in a subsequent steady tone. Measurement entails a
      test stimulus changing in sound level to null any aftereffect, so that loudness
      is perceived as steady. Previous studies have shown that the aftereffects are
      frequency dependent: Carrier frequencies of adapting and test stimuli must be
      closely matched for the greatest aftereffects. In the present study, frequency
      independent components were also indicated: Despite separation between adapting
      and test frequencies of up to two octaves, measurements always differed after
      decreasing and increasing sound-level adaptation, such that frequency functions
      for the two directions of adaptation never crossed. According to evidence from
      other negative adaptation effects in the auditory modality, explanation of the
      present aftereffects requires at least two mechanisms: Frequency-dependent
      components may reflect sensory processing, whereas frequency-independent
      components may be nonsensory in origin.

PMID- 7714504
TI  - Colors and emotions: preferences and combinations.
AB  - Within three age groups (7-year-old children, 11-year-old children, and adults),
      preferences for colors and emotions were established by means of two distinct
      paired-comparison tasks. In a subsequent task, participants were asked to link
      colors to emotions by selecting an appropriate color. It was hypothesized that
      the number of times that each color was tied to a specific emotion would be
      predictable from the separate preferences for colors and emotions. Within age
      groups, participants had consistent preferences for colors and emotions, but
      preferences differed from one age group to another. Especially in the youngest
      group, the pattern of combinations between colors and emotions appeared to be
      meaningfully related to the preference order for colors and emotions.

PMID- 7714506
TI  - Future time perspective and life events across adulthood.
AB  - Age differences in future time perspective and the relations between future time
      perspective, locus of control, and past and anticipated future life events were
      examined in younger (ages 20 to 37) and older (ages 60 to 81) men and women.
      There were neither age nor gender differences in the time period participants
      reported thinking of most frequently. Participants reported thinking about the
      next few months more frequently than about other future time periods, which
      ranged from the next few days to many years. However, younger participants also
      reported thinking frequently about more distant time periods, whereas older
      subjects did not. Anticipation of discontinuous future events, control of
      impending events, and positive past events accounted for some age differences
      found in thinking about distant future time periods. No systematic gender
      differences were found.

PMID- 7714508
TI  - Dehumanizing developments in American psychiatry in recent decades.

PMID- 7714507
TI  - The humanity of psychotic persons and their rights.

PMID- 7714509
TI  - Psychotic patients with unclear diagnoses. A descriptive analysis.
AB  - This report describes the clinical characteristics of psychotic patients who
      received a 6-month longitudinal research diagnosis of psychosis not otherwise
      specified (NOS) or for whom no consensus diagnosis was reached. The reasons why
      these subjects could not be classified into a specific DSM-III-R category, their
      classification under the proposed DSM-IV criteria, their reclassification at 24
      month follow-up, and differences between these groups and patients with
      schizophrenia and affective disorders in demographic characteristics, initial
      clinical features, and short-term course are explored. Data were drawn from the
      first phase of the Suffolk County Mental Health Project. Longitudinal consensus
      procedures were used to derive 6- and 24-month DSM-III-R diagnoses based on
      information from a structured diagnostic interview, an interview with the
      patient's clinician, the medical record and discharge summary, and significant
      others. Thirteen subjects (4.7%) received a diagnosis of psychosis NOS, and 12
      (4.3%) had no consensus diagnosis. Seven with psychosis NOS had an acute onset
      with rapid remission; this subgroup met DSM-IV criteria for brief psychosis
      without stressors. As a group, the psychosis NOS subjects were significantly
      older and had a lower rate of lifetime alcohol abuse/dependence than the
      schizophrenic and affective disorder groups. Their short-term course was
      significantly better than that of the schizophrenics and similar to that of
      patients with an affective disorder. Subjects with no consensus diagnosis were
      more likely to have lifetime drug abuse/dependence than the other two
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714510
TI  - Self-defeating personality disorder. A cross-national study of clinical utility.
AB  - The clinical utility of the DSM-II-R-proposed diagnostic category self-defeating
      personality disorder (SDPD) was assessed through the presentation of prototypic
      case histories to American and British psychiatrists and clinical psychologists.
      The most frequent diagnoses assigned were SDPD and personality disorder not
      otherwise specified; no alternative diagnoses were consistently provided. More
      than one in two professionals reported treating patients with a condition similar
      to the SDPD cases, and approximately 65% of these patients were reported to be
      female. American and British nonpatients were also assessed through the
      administration of an SDPD self-report questionnaire. The results suggest that the
      reported high prevalence of SDPD in the practitioners' patients is not a result
      of the expression of a general personality trait, and the reported greater
      incidence of SDPD in women is not a reflection of a normal, culturally learned,
      female behavior pattern.

PMID- 7714511
TI  - Psychometric properties of the Dissociative Experiences Scale.
AB  - The test-retest reliability of the Dissociative Experiences Scale (DES; Bernstein
      EM, Putnam FW [1986] Development, reliability, and validity of a dissociation
      scale. The Journal of Nervous and Mental Disease 174:727-735) in a clinical
      sample was found to be .93 for the total DES score and .95, .89, and .82 for the
      three subscale scores of amnesia, depersonalization-derealization, and absorption
      (dissociative identity disorder [DID], DSM-IV), respectively. Test-retest
      reliabilities within diagnostic groups of multiple personality disorder,
      dissociative disorder not otherwise specified, and a general other category of
      psychiatric diagnoses were obtained for total and subscale scores on the DES.
      These ranged from .78 to .96. Tests of mean scores across the two test sessions
      showed the total and subscale scores to be temporally stable. The DES was also
      found to be highly internally consistent: Cronbach's alphas of .96 and .97 were
      observed for the total DES scores taken at times 1 and 2, respectively. Construct
      validity of the DES was demonstrated by differentiation among the subscale scores
      in a repeated-measures analysis of variance (F[2,154] = 32.03, p < or = .001).
      Normality and general distribution issues were also addressed and provided a
      rationale for using the DES with parametric statistics. Reasons why the DES (as
      it was originally designed) is not appropriate as a dependent measure in outcome
      research are discussed, along with needed future research. Implications of the
      findings for the clinical usefulness of the DES as a diagnostic instrument are
      noted.

PMID- 7714512
TI  - Positive and negative symptoms in dissociative identity disorder and
      schizophrenia: a comparative analysis.
AB  - A substantial number of patients with dissociative identity disorder have had
      previous diagnoses of schizophrenia, due to the presence of positive symptoms of
      schizophrenia. The authors investigated the pattern of positive and negative
      symptoms in patients with dissociative identity disorder, and compared it with
      norms in schizophrenia. A total of 108 patients with a clinical diagnosis of
      dissociative identity disorder were administered the Positive and Negative
      Syndrome Scale. The positive symptom and general psychopathology scores were
      significantly more severe in the dissociative identity group than the norms for
      schizophrenia, while the negative symptoms were significantly more severe in
      schizophrenia. Since patients with dissociative identity disorder report more
      positive symptoms of schizophrenia than do schizophrenics, while schizophrenics
      report more negative symptoms, a primary emphasis on positive symptoms may result
      in false-positive diagnoses of schizophrenia and false-negative diagnoses of
      dissociative identity disorder.

PMID- 7714513
TI  - Symptom improvement and its temporal course in short-term dynamic psychotherapy.
      A growth curve analysis.
AB  - Using hierarchical linear model procedures, growth curve analyses were performed
      to examine the course, rate, and correlates of symptom improvement during short
      term anxiety-provoking psychotherapy (STAPP) and a 2-year posttermination period.
      The Symptom Check-list-90 was used to measure general symptomatology. The sample
      consisted of 15 patients who were found suitable for STAPP. Most had a diagnosis
      of anxiety. Therapists were in postgraduate manual-guided STAPP training. Results
      showed that three of four patients made a reliable and clinically significant
      symptom improvement over the course of treatment. Patients improved at a steady
      rate during treatment as well as after treatment. Average improvement was large
      and significant during treatment, while small and marginally significant after
      treatment. Improvement rates varied significantly over the course of treatment
      and were faster for patients less rigid in their personality functioning.

PMID- 7714515
TI  - Gender differences and similarities in African-American crack cocaine abusers.
AB  - Recent interest in women's health and patient-treatment matching has focused
      attention on gender differences among substance abusers. This article seeks to
      extend research in this area to African-American crack cocaine abusers. It
      describes gender differences and similarities in a large sample (652 males and
      595 females) of this important group of patients at a publicly funded, inner-city
      intensive outpatient clinic. As in previous studies on white working-class
      inpatients, few significant gender differences were found on demographic
      characteristics or drug use or treatment histories. Moreover, there were few
      differences in psychiatric symptomatology, and none in treatment participation or
      retention. In contrast to some reports, we did not find that women entered
      treatment with higher levels of depression than men. Most statistically
      significant differences we found were either too small to be of practical
      importance, or reflected conventional gender differences (e.g., women were more
      likely to care for dependents).

PMID- 7714514
TI  - Differential symptom reduction in depressed cocaine abusers treated with
      psychotherapy and pharmacotherapy.
AB  - We evaluated treatment response for depressed versus nondepressed ambulatory
      cocaine abusers in a 12-week randomized controlled trial of desipramine and
      cognitive-behavioral treatment, alone and in combination. Subjects with
      depressive symptomatology at baseline tended to have better retention and better
      cocaine outcomes compared with nondepressed subjects. Desipramine was an
      effective antidepressant in this sample and was associated with significantly
      greater reduction in depressive symptoms than was placebo; however, desipramine
      treatment was not associated with greater reductions in cocaine use for either
      the depressed or euthymic subgroup. Cognitive-behavioral relapse prevention
      treatment was associated with significantly longer periods of consecutive
      abstinence and better retention compared with supportive clinical management for
      the depressed subgroup, but psychotherapy condition did not have an effect on
      depressive symptoms. These data point to differential symptom reduction in
      depressed cocaine addicts and underscore the importance of evaluating combined
      psychotherapy-pharmacotherapy approaches for this population.

PMID- 7714516
TI  - Posttraumatic stress in volunteer firefighters. Predictors of distress.
AB  - Posttraumatic stress was studied in volunteer firefighters who regularly engage
      in threatening situations. In response to a survey of firefighters across New
      South Wales, Australia, 751 firefighters completed questionnaires concerning
      trauma experiences and posttraumatic stress levels. The presence of posttraumatic
      stress was best predicted by a combination of event-related and response-related
      aspects of the trauma. Firefighters' proximity to death, perceived severity of
      trauma, and fear of the traumatic event were closely associated with
      posttraumatic stress. In addition, the presence of stresses subsequent to the
      trauma, including unemployment and the loss of a loved one, was also related to
      posttraumatic stress. Findings are discussed in terms of etiological factors in
      posttraumatic stress and the need for adequate coping resources to manage the
      aftermath of a traumatic event.

PMID- 7714517
TI  - Evaluation of emotional state in deficit syndrome schizophrenia.

PMID- 7714518
TI  - Birth order and homosexuality.

PMID- 7714519
TI  - Segmental independence and age dependence of neurite outgrowth from embryonic
      chick sensory neurons.
AB  - Targets in limb regions of the chick embryo are further removed from the dorsal
      root ganglia that innervate them compared with thoracic ganglion-to-target
      distances. It has been inferred that axons grow into the limb regions two to
      three times faster than into nonlimb regions. We tested whether the differences
      were due to intrinsic properties of the neurons located at different segmental
      levels. Dorsal root ganglia (DRG) were isolated from the forelimb, trunk, and
      hind limb regions of stage 25-30 embryos. Neurite outgrowth was measured in
      dissociated cell culture and in cultures of DRG explants. Although there was
      considerable variability in the amount of neurite outgrowth, there were no
      substantive differences in the amount or the rate of outgrowth comparing
      brachial, thoracic, or lumbosacral neurons. The amount of neurite outgrowth in
      dissociated cell cultures increased with the stage of development. Overall, our
      data suggest that DRG neurons express a basal amount of outgrowth, which is
      initially independent of target-derived neurotrophic influences; the magnitude of
      this intrinsic growth potential increases with stage of development; and the
      neurons of the DRG are not intrinsically specified to grow neurites at rates that
      are matched to the distance they are required to grow to make contact with their
      peripheral targets in vivo. We present a speculative model based on Poisson
      statistics, which attempts to account for the variability in the amount of
      neurite outgrowth from dissociated neurons.

PMID- 7714520
TI  - Spontaneous bursting and long-lived local correlation in normal and denervated
      tectum of goldfish.
AB  - The formation of fine retinotopic order by growing optic fibers in the goldfish
      is thought to be mediated by the correlated firing of optic fibers from
      neighboring retinal ganglion cells. Although the activity of the tectal cells
      must also be important for this activity-dependent refinement, few studies have
      analyzed the pattern and local correlation of the intrinsic activity of tectal
      neurons and the effect of denervation on this activity. To address this issue,
      spontaneous (nonoptic driven) activity was analyzed and cross-correlograms were
      computed between individual tectal neurons using single and double electrode
      extracellular recordings. Recordings were made in normally innervated tectum in
      which the contribution of optic activity was eliminated by short-term intraocular
      blockade with tetrodotoxin and in denervated tecta in which the optic nerve had
      been severed several weeks prior. Several observations were relevant to activity
      dependent refinement: First, coupling between neighboring tectal cells is weak.
      Second, the time duration for local correlation is relatively long, as long as
      200 ms. Third, tectal neurons exhibit spontaneous bursting. Fourth, denervation
      increased the level of spontaneous activity in the tectum. The increased
      spontaneous activity and bursting following denervation implies that tectal
      neurons are more excitable when optic fibers are beginning to reinnervate the
      tectum. This could make it possible for optic fibers to drive tectal neurons at a
      time when their input to individual neurons is severely weakened by a lack of
      spatial convergence. The weak coupling between tectal cells and the consequent
      long-time constant for correlated activity implies a constraint on the duration
      of correlated retinal activity that is used for activity-dependent refinement.
      Since optic fibers likely need to detect the postsynaptic activity of a local
      group of tectal neurons, rather than that of a single neuron, the long tectal
      time constant means that retinal activity need not be correlated with precision
      much better than 200 ms because the postsynaptic circuitry cannot generate
      shorter correlations.

PMID- 7714521
TI  - Apolipophorin III is dramatically up-regulated during the programmed death of
      insect skeletal muscle and neurons.
AB  - The intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta,
      participate in the emergence behavior of the adult moth and then die during the
      subsequent 30 hours. In addition, several populations of interneurons and
      uniquely identified motor neurons also die after adult emergence. The trigger for
      all of these deaths is a decline in the circulating titer of the insect molting
      hormone 20-hydroxyecdysone. The ability of the muscles and neurons to die
      requires de novo gene expression. A differential hybridization screen of a
      "condemned" ISM cDNA library permitted the isolation of clones encoding four new
      up-regulated mRNAs. On sequencing, one of these recombinants was found to encode
      apolipophorin III (apoLp-III), a component of lipophorin, the major hemolymph
      lipoprotein of insects, previously shown to be synthesized in fat body. Although
      apoLp-III mRNA and protein were expressed at all stages of ISM development,
      levels of both molecules were dramatically elevated with the commitment of the
      cells to die. When ISM cell death was delayed by injection of 20-hydroxyecdysone,
      expression of apoLp-III at both the RNA and protein levels was markedly reduced
      at the normal time of cell death. Immunocytochemistry demonstrated that apoLp-III
      protein was abundantly expressed in the cytoplasm of dying muscles, interneurons,
      and identified motor neurons at the time of cell death. Apolipoproteins I and II,
      required components of lipophorin, were not expressed at detectable levels in the
      muscles or neurons. Furthermore, Western blots of native gels suggest that apoLp
      III was not associated with any other proteins. These data suggest that apoLp-III
      has activities independent of lipid transport that may play a role in programmed
      cell death. ApoLp-III joins apolipoproteins E and J (clusterin, sulfated
      glycoprotein-2) as a group of proteins that function in both lipid transfer and
      cell death.

PMID- 7714523
TI  - Birth times of neurons in labellar taste sensilla of the blowfly Phormia regina.
AB  - We studied the birth times of neurons of labellar taste sensilla in blowflies
      using incorporation of the thymidine analogue 5-bromodeoxyuridine (BrdU) as an
      indicator of birth time. We found that one of the two main sensillum types, the
      taste papillae, arise according to a clear spatial gradient of birth times,
      whereas the other sensillum type, taste hairs, arise without any apparent spatial
      ordering. Within each sensillum type, there was a strong tendency for either all
      or none of the neurons to have incorporated BrdU. Among those rare sensilla in
      which only some of the neurons incorporated BrdU, there were clear patterns of
      the distribution of labeled and unlabeled neurons per sensillum. These results
      suggest that subsets of the neurons of a sensillum are siblings, and thus argue
      against the possibility that the several neurons of a sensillum arise from a
      single stem cell precursor through repeated asymmetrical divisions.

PMID- 7714522
TI  - Effects of experience and juvenile hormone on the organization of the mushroom
      bodies of honey bees.
AB  - There is an age-related division of labor in the honey bee colony that is
      regulated by juvenile hormone. After completing metamorphosis, young workers have
      low titers of juvenile hormone and spend the first several weeks of their adult
      lives performing tasks within the hive. Older workers, approximately 3 weeks of
      age, have high titers of juvenile hormone and forage outside the hive for nectar
      and pollen. We have previously reported that changes in the volume of the
      mushroom bodies of the honey bee brain are temporally associated with the
      performance of foraging. The neuropil of the mushroom bodies is increased in
      volume, whereas the volume occupied by the somata of the Kenyon cells is
      significantly decreased in foragers relative to younger workers. To study the
      effect of flight experience and juvenile hormone on these changes within the
      mushroom bodies, young worker bees were treated with the juvenile hormone analog
      methoprene but a subset was prevented from foraging (big back bees).
      Stereological volume estimates revealed that, regardless of foraging experience,
      bees treated with methoprene had a significantly larger volume of neuropil in the
      mushroom bodies and a significantly smaller Kenyon cell somal region volume than
      did 1-day-old bees. The bees treated with methoprene did not differ on these
      volume estimates from untreated foragers (presumed to have high endogenous levels
      of juvenile hormone) of the same age sampled from the same colony. Bees prevented
      from flying and foraging nonetheless received visual stimulation as they gathered
      at the hive entrance. These results, coupled with a subregional analysis of the
      neuropil, suggest a potentially important role of visual stimulation, possibly
      interacting with juvenile hormone, as an organizer of the mushroom bodies. In an
      independent study, the brains of worker bees in which the transition to foraging
      was delayed (overaged nurse bees) were also studied. The mushroom bodies of
      overaged nurse bees had a Kenyon cell somal region volume typical of normal aged
      nurse bees. However, they displayed a significantly expanded neuropil relative to
      normal aged nurse bees. Analysis of the big back bees demonstrates that certain
      aspects of adult brain plasticity associated with foraging can be displayed by
      worker bees treated with methoprene independent of foraging experience. Analysis
      of the overaged nurse bees suggests that the post-metamorphic expansion of the
      neuropil of the mushroom bodies of worker honey bees is not a result of foraging
      experience.

PMID- 7714524
TI  - Dual pathways for tactile sensory information to thoracic interneurons in the
      cockroach.
AB  - The escape system of the American cockroach is both fast and directional. In
      response to wind stimulation both of these characteristics are largely due to the
      properties of the ventral giant interneurons (vGIs), which conduct sensory
      information from the cerci on the rear of the animal to type A thoracic
      interneurons (TIAs) in the thoracic ganglia. The cockroach also escapes from
      tactile stimuli, and although vGIs are not involved in tactile-mediated escapes,
      the same thoracic interneurons process tactile sensory information. The response
      of TIAs to tactile information is typically biphasic. A rapid initial
      depolarization is followed by a longer latency depolarization that encodes most
      if not all of the directional information in the tactile stimulus. We report here
      that the biphasic response of TIAs to tactile stimulation is caused by two
      separate conducting pathways from the point of stimulation to the thoracic
      ganglia. Phase 1 is generated by mechanical conduction along the animal's body
      cuticle or other physical structures. It cannot be eliminated by complete lesion
      of the nerve cord, and it is not evoked in response to electrical stimulation of
      abdominal nerves that contain the axons of sensory receptors in abdominal
      segments. However, it can be eliminated by lesioning the abdominal nerve cord and
      nerve 7 of the metathoracic ganglion together, suggesting that the relevant
      sensory structures send axons in nerve 7 and abdominal nerves of anterior
      abdominal ganglia. Phase 2 of the TIA tactile response is generated by a typical
      neural pathway that includes mechanoreceptors in each abdominal segment, which
      project to interneurons with axons in either abdominal connective. Those
      interneurons with inputs from receptors that are ipsilateral to their axon have a
      greater influence on TIAs than those that receive inputs from the contralateral
      side. The phase 1 response has an important role in reducing initiation time for
      the escape response. Animals in which the phase 2 pathway has been eliminated by
      lesion of the abdominal nerve cord are still capable of generating a partial
      startle response with a typically short latency even when stimulated posterior to
      the lesion.

PMID- 7714525
TI  - Ethanol influences on the chick embryo spinal cord motor system: analyses of
      motoneuron cell death, motility, and target trophic factor activity and in vitro
      analyses of neurotoxicity and trophic factor neuroprotection.
AB  - A series of in vivo and in vitro experiments were conducted to determine the
      influence of prenatally administered ethanol on several aspects of the developing
      chick embryo spinal cord motor system. Specifically, we examined: (1) the effect
      of chronic ethanol administration during the natural cell death period on spinal
      cord motoneuron numbers; (2) the influence of ethanol on ongoing embryonic
      motility; (3) the effect of ethanol exposure on neurotrophic activity in
      motoneuron target tissue (limb bud); and (4) the responsiveness of cultured
      spinal cord neurons to ethanol, and the potential of target-derived neurotrophic
      factors to ameliorate ethanol neurotoxicity. These studies revealed the
      following: Chronic prenatal ethanol exposure reduces the number of motoneurons
      present in the lateral motor column after the cell death period [embryonic day 12
      (E12)]. Ethanol tends to inhibit embryonic motility, particularly during the
      later stages viewed (E9-E11). Chronic ethanol exposure reduces the neurotrophic
      activity contained in target muscle tissue. Such diminished support could
      contribute to the observed motoneuron loss. Direct exposure of spinal cord
      neurons to ethanol decreases neuronal survival and process outgrowth in a dose
      dependent manner, but the addition of target muscle extract to ethanol-containing
      cultures can ameliorate this ethanol neurotoxicity. These studies demonstrate
      ethanol toxicity in a population not previously viewed in this regard and suggest
      a mechanism that may be related to this cell loss (i.e., decreased neurotrophic
      support).

PMID- 7714526
TI  - Dorsoventral patterning of the avian mesencephalon/metencephalon: role of the
      notochord and floor plate in suppressing Engrailed-2.
AB  - Transcription factors that are spatially and temporally restricted within the
      embryo may be used for dorsoventral and rostrocaudal positional information
      during development. The Engrailed-2 (En-2) gene is expressed across the
      mesencephalon/metencephalon (mes/met) boundary in the cerebellar primordium with
      strong dorsolateral expression and limited expression in the floor plate. In a
      previous experiment we demonstrated that, after removal of Hensen's node, embryos
      lacked a notochord in the head and the pattern of En-2 expression was normal
      rostrocaudally, but it was expanded into the ventral midline of the neural tube.
      This suggested that the notochord suppresses En-2 in the ventral neural tube
      during normal development. To test further the ability of the notochord (and
      floor plate) to suppress En-2, we transplanted ventral midline tissues from HH 5
      9 quail embryos beneath the rostral neural plate of HH 4-6 chick embryos. After
      24 hours in culture, 90% of the embryos with quail notochord or floor plate near
      the mes/met of the host lacked En-2 expression adjacent to the graft, and
      suppression was distance dependent. Enzymatically isolated notochords also
      suppressed En-2 (71%), but the results from isolated floor plates were
      inconclusive. Other grafts served as controls and included tissues from the trunk
      ventral midline, mes/met level dorsolateral neural plate, and trunk dorsolateral
      neural plate/somite. Collectively, the results suggest that during normal
      development the notochord and possibly the floor plate are important regulators
      of normal En-2 expression.

PMID- 7714527
TI  - Telencephalic and diencephalic origin of radial glial processes in the developing
      preoptic area/anterior hypothalamus.
AB  - Neuronal birth-dating studies using [3H] thymidine have indicated that neurons in
      the preoptic area/anterior hypothalamus (POA/AH) are derived primarily from
      progenitors in proliferative zones surrounding the third ventricle. Radial glial
      processes are potential guides for neuronal migration, and their presence and
      orientation during development may provide further information about the origin
      of cells in the POA/AH. In addition to determining the orientation of radial
      glial fibers, we examined the relationship of neurons with identified birth dates
      to radial glial processes in the developing POA/AH of ferrets. Neuronal birth
      dates were determined by injecting ferret fetuses with bromodeoxyuridine (BrdU)
      at several different gestational ages; brains were taken from ferret kits at
      subsequent prenatal ages. Sections were processed for immunocytochemistry to
      reveal vimentin or glial fibrillary acidic protein in radial glial, or BrdU
      labeled cell nuclei. Numerous radial glial processes extended from the lateral
      ventricles through ventral portions of the septal region to the pial surface of
      the POA/AH. These fibers both encapsulated and coursed ventrally through and
      around the anterior commissure of ferret, rat, and mouse fetuses. These ventrally
      directed fibers were less evident at older ages. In double-labeled sections from
      ferrets, BrdU-labeled cells in the dorsal POA/AH were often aligned in the same
      dorsal-ventral orientation as adjacent radial glial fibers. We suggest that a
      subset of neurons, originating in telencephalic proliferative zones, migrates
      ventrally along radial glial guides into the dorsal POA/AH.

PMID- 7714528
TI  - Differential estrogen accumulation among populations of projection neurons in the
      higher vocal center of male canaries.
AB  - The higher vocal center (HVC) of adult male canaries undergoes a seasonal change
      in volume that corresponds to seasonal modifications of vocal behavior: HVC is
      large when birds produce stereotyped song (spring) and is small when birds
      produce plastic song and add new song syllables into their vocal repertoires
      (fall). We reported previously that systemic exposure to testosterone (T)
      produces an increase in the volume of HVC similar to that observed with long-day
      photoperiods. T-induced growth of HVC occurred regardless of whether the borders
      of HVC were defined by Nissl-staining, the distribution of androgen-concentrating
      cells, or the distribution of projection neurons [separate neuronal populations
      within HVC project to the robust nucleus of the archistriatum (RA) and to Area X
      of the avian striatum (X)]. In the present study we used steroid autoradiography
      to determine whether T can influence the distribution of HVC cells that bind
      estrogen, and we combined estrogen autoradiography with retrograde labeling to
      determine whether HVC neurons that project to RA versus X differ in their ability
      to accumulate estrogen. Results showed that T increased the volume of Nissl
      defined HVC and although HVC contained a low density of estrogen-concentrating
      cells, T increased the spatial distribution of these cells to match the Nissl
      borders of HVC. We also identified a region containing a high density of estrogen
      concentrating cells located medial to HVC [we call this region paraHVC (pHVC)],
      and T also increased the volume of pHVC. pHVC also contained numerous X
      projecting neurons, but few if any RA-projecting neurons. Double-labeling
      analysis revealed that RA-projecting neurons did not accumulate estrogen, a small
      percentage of X-projecting neurons in HVC accumulated estrogen, and the majority
      of X-projecting neurons in pHVC showed heavy accumulation of estrogen. The data
      reported here and in our previous article suggest distinct roles for gonadal
      steroids within the HVC-pHVC complex: estrogens are concentrated by neurons that
      project to a striatal region that influences vocal production during song
      learning (X), whereas androgens are concentrated primarily by neurons that
      project to a motor region that is involved in vocal production during both song
      learning and the recitation of already-learned song (RA).

PMID- 7714529
TI  - New triterpenoid saponins from Mussaenda pubescens.
AB  - Three new triterpenoidal saponins, mussaendosides O [1], P [2], and Q [3] were
      isolated from whole plants of Mussaenda pubescens. These structures were
      elucidated on the basis of chemical and spectral methods, such as their 1H-1H
      COSY, HMQC, HMBC, TOCSY, and NOESY nmr spectra.

PMID- 7714530
TI  - Cyclopsychotride A, a biologically active, 31-residue cyclic peptide isolated
      from Psychotria longipes.
AB  - A preliminary characterization is provided of a naturally occurring cyclic
      peptide with interesting and potent biological activity. A 31-residue cyclic
      peptide, designated cyclopsychotride A [1], was obtained from the organic extract
      of the tropical plant, Psychotria longipes. Compound 1 inhibited [125I]
      neurotensin (NT) binding to HT-29 cell membranes (IC50 3 microM) and also
      stimulated increased levels of cytosolic Ca2+ in two unrelated cell lines that do
      not express NT receptors. The peptide was found to dose-dependently increase
      intracellular Ca2+ at concentrations ranging from 3 to 30 microM, and this
      response was not blocked by a known NT antagonist. Cyclopsychotride A [1]
      possesses three disulfide linkages and is thought to be the largest cyclic
      peptide isolated from a natural source. Both 1H-nmr and cd spectroscopy showed 1
      to be highly structured.

PMID- 7714531
TI  - Isolation and structures of sixteen new asbestinin diterpenes from the Caribbean
      gorgonian Briareum asbestinum.
AB  - Sixteen new diterpenoids, representative of the asbestinane skeletal class, have
      been isolated from shallow water colonies of the Caribbean gorgonian octocoral
      Briareum asbestinum. The structures of these secondary metabolites, named
      asbestinin-11 [1], asbestinin-12 [3], asbestinin-13 [4], asbestinin-14 [5],
      asbestinin-15 [7], asbestinin-16 [8], asbestinin-17 [9], asbestinin-18 [10],
      asbestinin-19 [11], asbestinin-20 [12], asbestinin-21 [13], asbestinin-22 [14],
      asbestinin-23 [15], 11-acetoxy-4-deoxyasbestinin E [16], 11-acetoxy-4
      deoxyasbestinin F [17] and 4-deoxyasbestinin G [18], were defined by chemical and
      spectroscopic methods. These specimens of B. asbestinum, collected in Puerto
      Rico, yielded almost exclusively diterpenoids possessing the asbestinane carbon
      skeleton thus suggesting minor biosynthetic variations for this gorgonian. In
      this paper, we also revise the structures of the known asbestinin-6 and
      asbestinin-7 to asbestinanes 2 and 6, respectively.

PMID- 7714532
TI  - Two new bioactive monotetrahydrofuran Annonaceous acetogenins from the bark of
      Xylopia aromatica.
AB  - Xylopien [1] and xylomatenin [2], two new bioactive monotetrahydrofuran
      Annonaceous acetogenins, have been isolated from an EtOH extract of the bark of
      Xylopia aromatica, using bioactivity-directed fractionation employing lethality
      to brine shrimp. These new compounds each have a double bond in the hydrocarbon
      chain and have been identified as C-23, C-24 dehydro analogs of xylopiacin and
      xylomaticin. Their structures were elucidated by spectral analyses of the parent
      compounds and/or simple chemical derivatives. Their absolute stereochemistries
      have been established by 1H- and 2D nmr experiments utilizing the production of
      Mosher esters. These acetogenins showed cytotoxic potencies superior to
      adriamycin against three human solid tumor cell lines.

PMID- 7714533
TI  - Cytotoxic cyclolignans from Koelreuteria henryi.
AB  - Chemical investigation of the cytotoxic fraction of Koelreuteria henryi resulted
      in the isolation of three cyclolignans. A new cyclolignan, named koelreuterin-1
      was elucidated as furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(8H)-one,5-(7-methoxy
      1, 3- benzodioxol-5-yl)[1]. Two known cyclolignans were characterized as
      austrobailignan-1 [2] and austrobailignan-2 [3]. The structure elucidation of 1
      was based on extensive 1H- and 13C-nmr spectral analyses. Further chemical
      conversion of 2 to 3 and oxidative transformation of 2 to 1 unambiguously
      confirmed the structure of 1. The cytotoxicity and tubulin polymerization
      inhibitory activity of 1-3 are discussed.

PMID- 7714534
TI  - Cytotoxic aromatic triterpenes from Maytenus ilicifolia and Maytenus
      chuchuhuasca.
AB  - The isolation and structure elucidation of four cytotoxic aromatic triterpenes [1
      4] along with three known quinoid triterpenes [5-7] from the South American
      medicinal plants Maytenus ilicifolia and M. chuchuhuasca are described. The
      structures of these aromatic triterpenes contained aromatized A rings and C-6
      oxygenated B rings, and were elucidated by 1H- and 13C-nmr spectroscopic studies
      and by X-ray crystallographic analysis of 3.

PMID- 7714535
TI  - Novel Ca(2+)-ATPase inhibitors from the dried root tubers of Polygonum
      Multiflorum.
AB  - The MeOH extract of the dried root tubers of Polygonum multiflorum yielded three
      bioactive compounds with an inhibitory activity on calmodulin-depleted
      erythrocyte calcium-dependent ATPase. These compounds were identified as E
      2,3,5,4'-tetrahydroxystilbene 2-O-beta-D-glucopyranoside [2] (IC50 = 240 microM)
      and cis- and trans-E-3-butylidene-4,5,6,7-tetrahydro-6,7-dihydroxy-1(3H)-
      isobenzofuranone [3 and 4](IC50 = 160 and 260 microM, respectively). E-2,4,6,4'
      Tetrahydroxystilbene 2-O-beta-D-glucopyranoside [1] was also isolated but was
      found to have no inhibitory effect on the enzyme.

PMID- 7714536
TI  - New delta 5,9 fatty acids in the phospholipids of the sea anemone Stoichactis
      helianthus.
AB  - The diunsaturated fatty acids 5,9-heneicosadienoic acid, 5,9-docosadienoic acid
      and 5,9-tricosadienoic acid, the brominated fatty acids 6-bromo- 5,9
      heneicosadienoic acid and 6-bromo-5,9-docosadienoic acid, and the polyunsaturated
      fatty acids 5,9,13-eicosatrienoic acid and 5,9,13-docosatrienoic acid, were
      identified for the first time in nature in the phospholipids (mainly
      phosphatidylethanolamine and phosphatidylserine) of the anemone Stoichactis
      helianthus. Structural elucidation was accomplished by means of mass spectrometry
      and chemical transformations such as pyrrolidide and dimethyldisulfide
      derivatization. Other delta 5,9 fatty acids such as 5,9-hexadecadienoic acid, 5,9
      octadecadienoic acid, and 5,9-eicosadienoic acid were also identified in the
      anemone. Our results indicate that delta 5,9 phospholipid fatty acids are not
      unique to sponges, as previously recognized, but can be found in other marine
      invertebrates such as an anemone. 24-Methylated sterols predominated in the
      sterol composition of the anemone investigated.

PMID- 7714537
TI  - Apiosporamide, a new antifungal agent from the coprophilous fungus Apiospora
      montagnei.
AB  - Bioassay-guided fractionation of an EtOAc extract from the mycelium of the
      coprophilous fungus Apiospora montagnei has furnished a new antifungal
      metabolite, named apiosporamide [1], and the known dihydroisocoumarin cis-(3R,4R)
      4-hydroxymellein [4]. The structure of 1 was assigned on the basis of HMBC, HMQC,
      NOESY, and hrms data. Elucidation of the structure was complicated by the fact
      that several nmr signals appeared only under certain conditions.

PMID- 7714538
TI  - Phenylpropanoid glucosides from Aegiphila obducta.

PMID- 7714539
TI  - Biological effects of prenylated hydroquinones: structure-activity relationship
      studies in antimicrobial, brine shrimp, and fish lethality assays.
AB  - Twenty-three hydroquinone and quinone derivatives were assayed for antimicrobial
      effects and brine shrimp and fish lethalities, to establish relevant structure
      activity relationships (SAR). Linear 2-prenyl-1,4-hydroquinones used for bioassay
      were obtained either by isolation from the sponge Ircinia spinosula or by
      synthesis. Corresponding quinones, as well as hydroquinones possessing saturated
      side-chains composed of one to eight isopentane units, were also synthesized and
      biologically evaluated. Terpenoid 1,4-benzoquinones displayed moderate
      antimicrobial activity against three microorganisms, SAR studies indicate the
      optimum length of the side-chain is in the range of five to fifteen carbon atoms.

PMID- 7714540
TI  - Absolute stereochemistry of neohalicholactone from the brown alga Laminaria
      sinclairii.
AB  - Phytochemical analysis of an extract from the brown alga Laminaria sinclairii led
      to the isolation of neohalicholactone, a cyclopropyl-containing oxylipin
      previously isolated from a marine sponge, Halichondria okadai. Unequivocal
      stereochemical analysis of the C-15 hydroxyl group showed this isolate to be of
      opposite overall absolute stereochemistry compared to that proposed for
      halicholactone, a related compound from the sponge, and by our inference, sponge
      derived neohalicholactone. Comparison of chiroptical data for all three compounds
      indicates the absolute stereochemistry of the sponge compounds is most probably
      opposite to that previously proposed.

PMID- 7714541
TI  - Graminone B, a novel lignan with vasodilative activity from Imperata cylindrica.
AB  - Two novel lignans, graminones A [1] and B [2] have been isolated from Imperata
      cylindrica and their structures have been elucidated on the basis of their
      spectral data. Graminone B [2] showed inhibitory activity on the contraction of
      the rabbit aorta.

PMID- 7714542
TI  - 6-Hydroxymanzamine A and 3,4-dihydromanzamine A, new alkaloids from the Okinawan
      marine sponge Amphimedon Sp.
AB  - Two new beta-carboline alkaloids, 6-hydroxymanzamine A [1] and 3,4
      dihydromanzamine A [2], have been isolated from the Okinawan marine sponge
      Amphimedon sp. and their structures elucidated on the basis of nmr spectral data.

PMID- 7714543
TI  - Ophirapstanol trisulfate, a new biologically active steroid sulfate from the deep
      water marine sponge Topsentia ophiraphidites.
AB  - Ophirapstanol trisulfate [1], a new steroid trisulfate related to sokotrasterol
      trisulfate was isolated from a deep water marine sponge Topsentia ophiraphidites.
      Compound 1 exhibited significant inhibition in the guanosine diphosphate/G
      protein RAS exchange assay. The structure elucidation of 1 and ophirapstanol [2]
      by nmr spectroscopy is described.

PMID- 7714544
TI  - Unstable enol sulfates from a two-sponge association.
AB  - An inseparable two-sponge association, consisting of a Haliclona sp. and a
      choristid sponge, yielded two unstable enol sulfates, (1E)-2- (3',4'
      dihydroxyphenyl)ethylene sulfate [3] and (1Z)-2-(3',4'-dihydroxyphenyl)ethylene
      sulfate [4]. Methanolysis converted the enol sulfates into 2-(3',4'
      dihydroxyphenyl)-1,1,2-trimethoxyethane [5] by an oxidative mechanism.

PMID- 7714545
TI  - Absolute stereochemistry of natural 3,4-dihydroxy-beta-ionone glycosides by the
      CD exciton chirality method.

PMID- 7714546
TI  - p53 immunoreactivity in oligodendrogliomas.
AB  - Data are presented on p53 protein presence in human oligodendrogliomas whose
      progress from low grade to anaplastic oligodendroglioma can be followed.
      Expression was evaluated by formalin-fixed paraffin-embedded section
      immunohistochemistry, using monoclonal PAb 1801 antibody. The frequency of p53
      protein accumulation is related to the stage of tumor malignancy. All the samples
      (100%) of malignant oligodendrogliomas were positive for p53 protein. Of 14 type
      II oligodendroglioma samples, 9 were positive (64%) while among type I
      oligodendroglioma the positivity was 28%. The mean proportion of reactive cells
      was also higher in malignant oligodendrogliomas. However, mean intensity staining
      did not differ among various grades of tumors. Our results point to the direct
      link between p53 protein accumulation and the malignant stage of human
      oligodendrogliomas. However, the value of p53 protein accumulation in predicting
      malignant behavior of oligodendrogliomas requires further confirmation.

PMID- 7714547
TI  - Peripheral benzodiazepine receptors and glucose metabolism in human gliomas.
AB  - Peripheral benzodiazepine receptors (PBR) are increased in gliomas and augmented
      glucose metabolism is seen in malignant brain tumors. We investigated the
      relationship between PBR density (Bmax) and glucose utilization rate (GUR) in 17
      patients with cerebral gliomas of different grades. PBR Bmax was assessed by
      [3H]PK-11195 in vitro binding in surgical specimens and GUR was measured by
      Positron Emission Tomography with [18F]2-Fluorodeoxyglucose before the surgery.
      In untreated tumors there was a positive correlation between PBR Bmax and GUR (2r
      = 0.84). This correlation was not observed in patients who had been treated with
      radiation and/or chemotherapy prior to surgery (r2 = 0.13). In addition, in
      untreated patients, the increase in PBR density and GUR appeared to be related to
      the degree of malignancy.

PMID- 7714548
TI  - Cell death due to ACNU-induced DNA fragmentation: inhibition by cycloheximide.
AB  - Several anticancer drugs have recently been shown to induce cell death in a
      manner similar to programmed cell death or apoptosis. The purpose of this study
      is to explore the mode of cell death caused by ACNU, a water-soluble nitrosourea.
      Exposure of rat glioma cell line KEG-1 to ACNU for 2 hours resulted in
      oligonucleosomal DNA fragmentation, creating a 'ladder' on agarose gel
      electrophoresis. DNA fragmentation began 18 hours after ACNU treatment, and
      preceded loss of membrane integrity as evaluated by the trypan blue exclusion
      test. The extent of DNA fragmentation increased in a dose-dependent manner, and
      the cell survival rate decreased reciprocally. A translational inhibitor,
      cycloheximide, suppressed this DNA fragmentation and enhanced cell survival rate
      with partial inhibition of protein synthesis. However, a transcriptional
      inhibitor, actinomycin D, failed to inhibit DNA fragmentation or enhance cell
      survival. Cycloheximide-inhibitable DNA fragmentation was also found in the KEG-1
      implanted in vivo rat model following the administration of ACNU. These findings
      suggest that ACNU induces cell death associates with DNA fragmentation and
      partially with protein synthesis.

PMID- 7714549
TI  - TM-1 cells from an established human malignant glioma cell line produce PDGF, TGF
      alpha, and TGF-beta which cooperatively play a stimulatory role for an autocrine
      growth promotion.
AB  - We have previously established a human malignant glioma cell line, TM-1. TM-1
      cells could proliferate in the serum-free medium. In the present study,
      immunochemical analysis demonstrated that platelet-derived growth factor (PDGF),
      transforming growth factor (TGF)-alpha, and TGF-beta are present in the serum
      free medium conditioned by growing TM-1 cells. While the cells appeared to
      possess a single type of binding sites for epidermal growth factor (EGF) with
      properties comparable to those determined for other tumor cells, the conditioned
      medium did not contain EGF.PDGF, TGF-alpha, and EGF added exogenously to serum
      free media stimulated thymidine incorporation into DNA of TM-1 cells. In
      addition, antibodies specific for PDGF and TGF-alpha suppressed this activity.
      These results indicate autocrine and stimulatory roles of PDGF and TGF-alpha for
      the proliferation of TM-1 cells. As observed for other tumor cells, TGF-beta by
      itself weakly suppressed thymidine incorporation by TM-1 cells. However, TGF-beta
      employed in combination with TGF-alpha or EGF appeared to stimulate thymidine
      incorporation, suggesting that a cooperative action of TGF-beta with different
      growth factors may be involved in the stimulatory growth regulation at least for
      TM-1 cells.

PMID- 7714550
TI  - Expression of estramustine-binding protein in ependymomas and in human and
      developing rat ependymal cells.
AB  - The mainstays of primary treatment of ependymoma are aggressive surgery followed
      by radiotherapy. Although spreading occasionally occurs in the cerebrospinal
      pathways, chemotherapy is still not established and no ultimate drug has so far
      been found. Estramustine-phosphate (EMP), with a demonstrated effect on
      astrocytoma in vitro, has been shown to penetrate the blood-tumor barrier and to
      accumulate in human brain tumor tissue including ependymoma. It has been proposed
      that the cytotoxic effect of EMP depends on the presence of a binding protein,
      estramustine-binding protein (EMBP). In the present paper we have, for the first
      time, immunohistochemically demonstrated an EMBP-like protein in a series of
      ependymomas. Immunoreactivity was found within the cytoplasm of the tumor cells
      with a tendency to increase with increasing malignancy of the tumor. In addition,
      the occurrence of EMBP-like protein was demonstrated in human ependymal cells. In
      the rat brain, a weak immunoreactivity was detected in early fetal
      neuroepithelial cells while the staining intensity was increased in mature
      ependymal cells in late fetal, neonatal, and adult rat. Thus; immunoreactivity
      for an EMBP-like protein was demonstrated in ependymoma tissue, normal human
      ependyma and in the developing rat ependymal cells.

PMID- 7714551
TI  - Superiority of PCNU over AZQ in the treatment of primary brain tumors: results of
      a prospective randomized trial (81-20) by the Brain Tumor Study Group.
AB  - PURPOSE: A two-arm randomized clinical trial was performed to determine the
      efficacy of PCNU and AZQ in the treatment of de novo or recurrent primary brain
      tumors. An additional objective was to gather information on the administration
      and toxicity of these compounds, supplementing that obtained previously in phase
      I/II studies. METHODS: During 1982 and 1983 the Brain Tumor Study Group
      randomized 152 adult patients with primary brain tumors to receive PCNU 75-100
      mg/m2 intravenously (IV) every 8 weeks or AZQ 15 mg/m2 IV once a week for 4
      weeks, every 6-8 weeks. All patients who had not received 'full dose'
      radiotherapy before randomization received it concurrently with the first course
      of protocol chemotherapy. The data were analyzed for the total randomized
      population (RP), and for 130 patients in the valid study group (VSG) formed by
      excluding 22 patients for whom the histologic diagnosis was not documented by
      central review. RESULTS: Median survival times were 11.0 months for the PCNU
      group and 8.4 months for the AZQ group. The difference in survival curves was
      statistically significant for the RP (p = 0.01) and the VSG (p = 0.02). Life
      table analysis of the VSG showed estimated 2-year survivals of 34% for PCNU and
      11% for AZQ. The advantage of PCNU remained significant (p = 0.006) after
      adjustment for histopathologic category, age, initial performance status, and
      interval from initial reported surgery. Myelosuppression was the principal
      toxicity in both groups.

PMID- 7714552
TI  - Scale for assessing quality of life of children survivors of cranial posterior
      fossa tumors.
AB  - BACKGROUND: Evaluation of quality of life of survivors of brain tumors is an
      important aspect of outcome that must be included in clinical studies. METHODS:
      We have developed a new scale for assessing quality of life (QL) of pediatric
      long-term survivors of posterior fossa tumors based on their physical,
      psychointellectual, and endocrine/growth status. We have studied 39 patients,
      with a median follow-up of 9 years. Twenty-five had cerebellar astrocytoma (CA),
      6 medulloblastoma (MDB), 5 brain-stem glioma (BSG) and 3 ependymoma of IV
      ventricle (EPD). RESULTS: Sixty-six percent of children showed neurologic and/or
      visual sequelae. Little or no significant disability (Bloom's levels I-II) were
      present in 66%. Psychointellectual dysfunction was present in 44%, with an IQ <
      90 in 39%. Endocrine and growth disorders were found in 26%, mostly stature
      anomalies. According to our scale, QL scores were high in 19 patients (49%),
      intermediate in 8 (20%), and low in the remaining 12 (31%). Unfavourable outcomes
      were related to age of less than 4 years, tumors other than CA (MDB, BSG, EPD),
      incomplete tumoral resection, and employment of radiotherapy and chemotherapy.
      CONCLUSION: Our results are comparable to others previously reported, and this
      supports the validity of our scale. We consider that this scale is applicable to
      evaluate QL of children survivors of cranial tumors.

PMID- 7714553
TI  - Selective incorporation of 111In-labeled PHOTOFRIN by glioma tissue in vivo.
AB  - The use of PHOTOFRIN for photodynamic therapy of human gliomas has been studied
      by i.v. administration and laser photosensitization. Defining the uptake of
      PHOTOFRIN in the patient's tumor in comparison with the surrounding normal brain
      tissue is highly desirable for patient selection and study of in vivo kinetics.
      We utilized a non-invasive approach to the detection of PHOTOFRIN uptake in brain
      tumors with 111In-oxine radiolabeled PHOTOFRIN and external imaging and
      quantitation using a gamma camera. Biodistribution of 111In-labeled PHOTOFRIN in
      13 organs was determined in four dogs and 15 mice with gliomas. 99mTc-DTPA was
      used as a control for nonspecific uptake. The greatest concentration of 111In
      PHOTOFRIN in the brain tumor occurred at 24 hours post i.v. administration. The
      brain tumor PHOTOFRIN uptake was seven times greater than that of normal brain.
      The decreased blood background at 72 hours made this the optimum time for
      imaging. Specific tumor tissue uptake of 111In-PHOTOFRIN occurred, well beyond
      that resulting from blood-brain-barrier (BBB) breakdown.

PMID- 7714554
TI  - Management of intracranial metastases of differentiated carcinoma of thyroid.
AB  - Brain metastases in differentiated carcinoma of the thyroid is a rare occurrence.
      We treated five documented cases of carcinoma of thyroid with brain metastases
      out of 400 cases of thyroid cancer treated between 1972 to 1993. 4 were females
      out of which one was pregnant during the appearance of brain metastases. All
      cases were treated with thyroidectomy, and radioiodine as primary therapy. Brain
      metastases developed 6 months to 11 years following treatment of the primary and
      were treated with radiotherapy and suppressive levothyroxine. We observed the
      beneficial effect of suppressive thyroxine and the poor prognosis associated with
      pregnancy and withdrawal of thyroid replacement therapy. 3 of the 5 patients are
      alive 12-23 months after treatment for brain metastases, while 2 patients died at
      4 months and 7 years post brain metastases due to pulmonary and hepatic failure,
      respectively.

PMID- 7714555
TI  - Effects of superior temporal polysensory area lesions on eye movements in the
      macaque monkey.
AB  - 1. On the basis of its anatomic connections and single-unit properties, the
      superior temporal polysensory area (STP) would seem to be primarily involved in
      visuospatial functions. We have examined the effects of lesions of STP on
      saccadic eye movements, visual fixation, and smooth pursuit eye movements to
      directly test the hypothesis that STP is involved in visuospatial and visuomotor
      behavior. 2. Seven monkeys were trained to make saccades to targets 8, 15, and 22
      degrees from a central fixation point along the horizontal meridian and 8 degrees
      from the central fixation point along the vertical meridian. One monkey was also
      trained to make saccades to auditory targets. The same monkeys were trained to
      foveate a stationary central fixation point and to follow it with a smooth
      pursuit eye movement when it began moving 5, 13, or 20 degrees/s. Four monkeys
      received unilateral STP lesions, one received a bilateral STP lesion, and as a
      control, two received unilateral inferior temporal cortex (IT) lesions. After
      testing, three of the animals with unilateral STP lesions received an additional
      STP lesion in the hemisphere contralateral to the first lesion. Similarly, one
      animal with a unilateral IT lesion received an additional IT lesion in the
      hemisphere contralateral to the first lesion. 3. All monkeys with complete
      removal of STP showed a significant increase in saccade latency to the most
      peripheral contralateral target, and most also had increased saccade latencies to
      the other contralateral targets. Saccades directed to targets along the vertical
      meridian or toward targets in the hemifield ipsilateral to the lesion were not
      impaired by removal of STP. By contrast, IT lesions did not impair the monkeys'
      ability to make saccadic eye movements to visual stimuli at any location, showing
      that saccades to visually guided targets are not impaired nonspecifically by
      damage to visual cortex. 4. The deficit in making eye movements after STP lesions
      was specific to saccade latency, with little effect on the accuracy of saccades
      to visual targets. 5. In the one monkey trained to make saccades to auditory
      targets, removal of STP did not impair saccades to auditory targets contralateral
      to its lesion, despite this monkey showing the largest increase in saccades
      latencies to visual targets. 6. There was complete recovery of saccade latency to
      the baseline level of performance on the saccade task after all STP
      lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714556
TI  - Amplitude modulation of the soleus H reflex in the human during active and
      passive stepping movements.
AB  - 1. It was hypothesized that passive movement of either the whole leg or its
      separate segments, in a manner mimicking human gait, leads to attenuation of the
      soleus H reflex. It was further hypothesized that this attenuation arises from
      presynaptic effects. Reflex amplitudes were observed in humans during natural
      bipedal and unipedal stepping on the spot, during passive stepping, during
      passive movement of the lower limb segments about the hip, knee, and ankle
      individually in a stepping fashion, and during passive movement with tonic
      contraction of the soleus muscle. 2. In natural stepping at a cadence of 54
      steps/min, the reflex means were substantially depressed in the swing phase (P <
      0.01). (Means, standing control 90.1%, unipedal 8.3%, bipedal 6.9%, of maximum M
      wave.) During the stance phase, reflex magnitudes were mildly and significantly
      elevated in four of six subjects, compared with standing controls (P < 0.05). 3.
      For passive stepping, subjects were dorsally tilted 20 and 90 degrees (lying
      supine) from the vertical position, to obtain quiet electromyograms (EMGs) in the
      postural muscles. Recorded during natural stepping, the right leg was manipulated
      to match the electrogoniometer traces of the three major joints. 4. At 20 degrees
      of tilt of the body, mean H reflexes were significantly lower, by 26.4%, compared
      with the supine position (P < 0.05). During passive stepping movement of the leg
      at 54 steps/min, the reflex was profoundly attenuated over the entire cycle (P <
      0.01). The significantly attenuated reflexes during active stepping and during
      passive stepping movement of the whole leg were not significantly different at
      the point where the limb approached full flexion in the swing phase (P > 0.48).
      This was the case for measurements made at either body position, 20 degrees
      dorsal tilt or supine. 5. Passive flexion-extension, around either the hip or the
      knee, significantly inhibited the mean reflex magnitude close to full flexion, at
      either body position (P < 0.01). Such movement around the ankle resulted in
      significant inhibition of the reflex in two of the four subjects (P < 0.05). The
      numeric sum of the reflex depression arising from the flexion-extension of the
      individual joints was greater than that arising from movement of the whole limb.
      6. With the ankle braced, the significant reflex attenuation remained when a
      tonic isometric contraction of the soleus muscle was introduced. This suggests
      premotoneuronal mechanisms for the inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714557
TI  - Novel interneuron having hybrid modulatory-central pattern generator properties
      in the feeding system of the snail, Lymnaea stagnalis.
AB  - 1. We used intracellular recording techniques to examine the role of a novel type
      of protraction phase interneuron, the lateral N1 (N1L) in the feeding system of
      the snail Lymnaea stagnalis. 2. The N1Ls are a bilaterally symmetrical pair of
      electrotonically coupled interneurons located in the buccal ganglia. Each N1L
      sends a single axon to the contralateral buccal ganglia. Their neurite processes
      are confined to the buccal neuropile. 3. In the isolated CNS, depolarization of
      an N1L is capable of driving a full (N1-->N2-->N3), fast (1 cycle every 5 s)
      fictive feeding rhythm. This was unlike the previously described N1 medial (N1M)
      central pattern generator (CPG) interneurons that were only capable of driving a
      slow, irregular rhythm. Attempts to control the frequency of the fictive feeding
      rhythm by injecting varying amounts of steady current into the N1Ls were
      unsuccessful. This contrasts with a modulatory neuron, the slow oscillator (SO),
      that has very similar firing patterns to the N1Ls, but where the frequency of the
      rhythm depends on the level of injected current. 4. The N1Ls' ability to drive a
      fictive feeding rhythm in the isolated preparation was due to their strong,
      monosynaptic excitatory chemical connection with the N1M CPG interneurons. Bursts
      of spikes in the N1Ls generated summating excitatory postsynaptic potentials
      (EPSPs) in the N1Ms to drive them to firing. The SO excited the N1M cells in a
      similar way, but the EPSPs are strongly facilitatory, unlike the N1L-->N1M
      connection. 5. Fast (1 cycle every 5 s) fictive feeding rhythms driven by the N1L
      occurred in the absence of spike activity in the SO modulatory neuron. In
      contrast, the N1L was usually active in SO-driven rhythms. 6. The ability of the
      SO to drive the N1L was due to strong electrotonic coupling, SO-->N1L. The weaker
      coupling in the opposite direction, N1L-->SO, did not allow the N1L to drive the
      SO. 7. Experiments on semintact lip-brain preparations allowed fictive feeding to
      be evoked by application of 0.1 M sucrose to the lips (mimicking the normal
      sensory input) rather than by injection of depolarizing current. Rhythmic
      bursting, characteristic of fictive feeding, began in both the SO and N1L at
      exactly the same time, indicating that these two cell types are activated in
      "parallel" to drive the feeding rhythm. 8. The N1L is also part of the CPG
      network. It Excited the N2s and inhibited the N3 phasic (N3p) and N3 tonic (N3t)
      CPG interneurons like the N1Ms.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714558
TI  - Stimulus-evoked changes of extra- and intracellular pH in the leech central
      nervous system. I. Bicarbonate dependence.
AB  - 1. We have measured the effect of repetitive electrical nerve root stimulation on
      the extracellular potassium activity (aKe) and the extracellular pH (pHe) and
      intracellular pH (pHi) in segmental ganglia of the leech Hirudo medicinalis with
      double-barreled K(+)- and pH-sensitive microelectrodes. To investigate the
      influence of CO2/HCO3-, we compared the stimulus-evoked changes in aKe, pHe, and
      pHi in the presence and absence of 5% CO2-24 mM HCO3- in the saline. 2. An
      electrical nerve root stimulation at 20-30 Hz for 1 min caused a rapid increase
      of 1.11 +/- 0.79 (SD) mM in aKe, followed by an aKe undershoot of 0.17 +/- 0.15
      mM when the stimulation was discontinued (n = 6). aKe transients were not
      significantly affected by CO2/HCO3-. 3. In 5 mM N-2-hydroxyethylpiperazine-N'-2
      ethanesulfonic acid (HEPES)-buffered, nominally CO2/HCO3(-)-free saline, low
      stimulus intensities or stimulus durations up to a few seconds resulted in a fast
      alkaline pHe transient. This alkalinization was followed by a larger and longer
      lasting extracellular acidification when the stimulation was intensified and
      prolonged. A stimulation at 20 Hz, 5 V for 1 min caused an average alkaline shift
      of 0.083 +/- 0.055 pH units, followed by an acidosis of 0.079 +/- 0.038 pH units
      (n = 63). A change from 5 mM HEPES-buffered saline to 20 mM HEPES-buffered saline
      attenuated the stimulus-evoked pHe transients by 50-60%.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7714559
TI  - Stimulus-evoked changes of extra- and intracellular pH in the leech central
      nervous system. II. Mechanisms and maintenance of pH homeostasis.
AB  - 1. We have studied extracellular pH (pHe) and intracellular pH (pHi) changes
      evoked by repetitive electrical side nerve stimulation (20 Hz, 1 min) in
      segmental ganglia of the leech Hirudo medicinalis using double-barreled, pH
      sensitive microelectrodes to elucidate the involvement of neurotransmitters, of
      carbonic anhydrase, and of active acid/base transport on the extracellular H+
      homeostasis. In saline buffered with 5% CO2-24 mM HCO3-, the stimulation induced
      a small and brief alkalinization followed by an acidification in the
      extracellular spaces (ECS), whereas neurons acidified and glial cells alkalinized
      (see previous paper). 2. Blocking synaptic transmitter release by superfusion
      with 20 mM Mg2+ saline (CO2/HCO3(-)-free) led to a reversible reduction of both
      activity-induced pHe changes by approximately 90% and to a complete suppression
      of the intracellular acidification of neurons. After application of the
      glutamate/kainate receptor blocker 6-cyano-7-dinitroquinozaline-2,3-dione (CNQX,
      50 microM) to CO2/HCO3(-)-free saline, the stimulus-evoked pHe changes were
      reversibly reduced. The gamma-aminobutyric acid-A (GABAA) receptor antagonist
      picrotoxin (50 microM) led to an amplification of the extracellular
      alkalinization in the presence of CO2/HCO3-. Bath application of the excitatory
      transmitter agonists carbachol or kainate to CO2/HCO3(-)-free saline induced
      biphasic alkaline-acid transients in the ECS; the inhibitory transmitters GABA
      and serotonin had no detectable effects on the pHe (saline buffered with CO2/HCO3
      ).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714560
TI  - Level dependence of cochlear nucleus onset unit responses and facilitation by
      second tones or broadband noise.
AB  - 1. The responses of onset units in the cochlear nucleus of the anesthetized
      guinea pig have been measured to single tones, two-tone complexes, and broadband
      noise (BBN; 20-kHz bandwidth). The onset units were subdivided into three groups,
      onset-I (OnI), onset-L (OnL), and onset-C (OnC), on the basis of a decision tree
      using their peristimulus time histogram (PSTH) shape and discharge rate in
      response to suprathreshold best-frequency (BF) tone bursts. 2. PSTHs were
      constructed from responses either to single tones at a unit's BF or to BBN as a
      function of level. When sufficient sustained activity could be elicited from the
      unit, arbitrarily defined as > 100 spikes/s, a coefficient of variation (CV) was
      calculated; the majority were characterized by a CV that was similar to transient
      chopper units (0.35 < CV < 0.5). First spike latency decreased monotonically with
      increasing sound level. For the majority of onset units, the first spike timing
      was very precise. 3. BF rate-level functions recorded from OnL and OnC units did
      not show any signs of discharge rate saturation at the highest sound levels we
      have used (100-115 dB SPL). No systematic relationship was observed between the
      threshold at BF and the shape of the rate-level function. BBN rate-level
      functions were typically characterized by higher discharge rates than in response
      to BF tones. However, for OnI units and a minority of other onset units, there
      was little difference in the shape of their rate-level functions in response to
      BF tones or BBN. 4. The threshold of most onset units to BBN was similar to the
      threshold to a BF tone that had similar overall root-mean-square (RMS) energy.
      The BBN threshold was, on average, 5.5 dB greater than the BF threshold. This
      result contrasts with that found in auditory-nerve fibers recorded in the same
      species, with the use of an identical sound system, where the threshold to BBN
      was, on average, 19.4 dB higher. The mean threshold difference between BBN and BF
      tones for a population of chopper units recorded in the same series of
      experiments was 17.7 dB. The relative thresholds to BBN and BF tones indicated
      that the bandwidths near the onset units' BF threshold were broader than could be
      estimated with the use of single tones. Ten units were characterized by bimodal
      response areas.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714561
TI  - Separation and identification of multiple potassium currents regulating the
      pacemaker activity of insect neurosecretory cells (DUM neurons).
AB  - 1. Whole cell voltage-clamp studies performed in isolated adult neurosecretory
      cells identified as dorsal unpaired median (DUM) neurons of the terminal
      abdominal ganglion of the cockroach Periplaneta americana have allowed us to
      reveal a complex voltage-dependent outward current regulating the pacemaker
      activity. 2. The global outward current remaining after tetrodotoxin treatment
      was activated by depolarization above -50 mV, showing steep voltage dependence
      and outward rectification. 3. We used tail current analysis to determine the
      ionic selectivity of this outward current. The reversal potentials for two
      extracellular potassium concentrations (-92.7 and -65.4 mV for 3.1 and 10 mM,
      respectively) is consistent with the expected equilibrium potential for potassium
      ions. 4. Both peak and sustained components of the global outward K+ current were
      reduced by external application of 20 mM tetraethylammonium chloride, 10 nM
      iberiotoxin, 1 nM charybdotoxin (CTX) and 1 mM cadmium chloride. Subtraction of
      current recorded in CTX solution from that in control solution revealed an
      unusual biphasic Ca(2+)-dependent K+ current. The fast transient current
      resistant to 5 mM 4-aminopyridine (4-AP) is distinguished by its dependence on
      holding potential and time course from the late sustained current. 5. In
      addition, two other components of CTX-resistant outward K+ current could be
      separated by sensitivity to 4-AP, time course, and voltage dependence. Beside a
      calcium-independent delayed outwardly rectifying current, a 4-AP-sensitive fast
      transient current resembling the A-current has been also identified. It activates
      at negative potential (about -65 mV) and unlike the A-current of other neurons,
      it inactivates rapidly with complex inactivation kinetics. A-like current is half
      inactivated at -63.5 mV and half-activated at -35.6 mV. 6. Our findings
      demonstrate for the first time in DUM neuron cell bodies the existence of
      multiple potassium currents underlying the spontaneous electrical activity. Their
      identification and characterization represent a fundamental step in further
      understanding the pacemaker properties of these insect neurosecretory cells.

PMID- 7714562
TI  - In vivo responses of single olfactory receptor neurons in the channel catfish,
      Ictalurus punctatus.
AB  - 1. We report for the first time in any teleost, a quantitative in vivo study of
      recordings from single olfactory receptor neurons (ORNs) in the channel catfish,
      Ictalurus punctatus, with odorant stimuli. 2. Responses of 69 spontaneously
      active single ORNs were recorded simultaneously with the electroolfactogram
      (EOG). Recording times ranged from 10 to 72 min per receptor cell with an average
      of 24 +/- 15 (SD) min/cell. The averaged spontaneous frequency ranged from < 1 to
      12 action potentials/s with a mean frequency of 4.7 +/- 2.5 action potentials/s.
      3. Catfish ORNs responded to the odorant stimuli (amino acids, bile salts, and
      ATP) with either an excitation or suppression of the background neural activity.
      Suppressive responses were encountered more frequently than excitatory responses,
      suggesting that suppressive responses also play an important role in olfactory
      coding. 4. Excitatory and suppressive responses to the different odorants were
      elicited from the same ORN, suggesting that different olfactory receptor
      molecules and different transduction pathways exist in the same ORN.

PMID- 7714564
TI  - Topography of intensity tuning in cat primary auditory cortex: single-neuron
      versus multiple-neuron recordings.
AB  - 1. We studied the spatial distributions of amplitude tuning (monotonicity of rate
      level functions) and response threshold of single neurons along the dorsoventral
      extent of cat primary auditory cortex (AI). To pool data across animals, we used
      the multiple-unit map of monotonicity as a frame of reference. Amplitude
      selectivity of multiple units is known to vary systematically along isofrequency
      contours, which run roughly in the dorsoventral direction. Clusters sharply tuned
      for intensity (i.e., "nonmonotonic" clusters) are located near the center of the
      contour. A second nonmonotonic region can be found several millimeters dorsal to
      the center. We used the locations of these two nonmonotonic regions as reference
      points to normalize data across animals. Additionally, to compare this study to
      sharpness of frequency tuning results, we also used multiple-unit bandwidth (BW)
      maps as references to pool data. 2. The multiple-unit amplitude-related
      topographies recorded in previous studies were confirmed. Pooled multiple-unit
      maps closely approximated the previously reported individual case maps when the
      multiple-unit monotonicity or the map of bandwidth (in octaves) of pure tones to
      which a cell responds 40 dB above minimum threshold were used as the pooling
      reference. When the map of bandwidth (in octaves) of pure tones to which a cell
      responds 10 dB above minimum threshold map was used as part of the measure, the
      pooled spatial pattern of multiple-unit activity was degraded. 3. Single neurons
      exhibited nonmonotonic rate-level functions more frequently than multiple units.
      Although common in single-neuron recordings (28%), strongly nonmonotonic
      recordings (firing rates reduced by > 50% at high intensities) were uncommon (8%)
      in multiple-unit recordings. Intermediately nonmonotonic neurons (firing rates
      reduced between 20% and 50% at high intensities) occurred with nearly equal
      probability in single-neuron (28%) and multiple-unit (26%) recordings. The
      remaining recordings for multiple units (66%) and single units (44%) were
      monotonic (firing rates within 20% of the maximum at the highest tested
      intensity). 4. In ventral AI (AIv), the topography of monotonicity for single
      units was qualitatively similar to multiple units, although single units were on
      average more intensity selective. In dorsal AI (AId) we consistently found a
      spatial gradient for sharpness of intensity tuning for multiple units; however,
      for pooled single units in Aid there was no clear topographic gradient. 5.
      Response (intensity) thresholds of single neurons were not uniformly distributed
      across the dorsoventral extent of AI.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714565
TI  - Short- and long-range neuronal synchronization of the slow (< 1 Hz) cortical
      oscillation.
AB  - 1. Multisite, extra- and intracellular recordings were carried out in cats under
      ketamine and xylazine anesthesia to assess the degree of synchrony and time
      relations among cellular activities in various neocortical fields during a slow
      (< 1 Hz) oscillation consisting of long-lasting depolarizing and hyperpolarizing
      phases. 2. Recordings were performed from visual areas 17, 18, 19, and 21,
      association suprasylvian areas 5 and 7, motor pericruciate areas 4 and 6, as well
      as some related thalamic territories, such as the lateral geniculate (LG),
      perigeniculate (PG), and rostral intralaminar nuclei. We used spike analyses
      (auto- and cross-correlograms) to reveal rhythmicities, time relations and
      coherence properties, analyses of field potentials recorded through the same
      microelectrodes as used for unit discharges (auto-and cross-correlation functions
      and their spectral equivalents), and spike-triggered averages. The results are
      based on 194 groups of neurons with a total of 591 neurons. Seventeen groups
      included intracellular recordings of cortical neurons with membrane potentials
      more negative than -60 mV and overshooting action potentials. 3. The most obvious
      and frequent signs of neuronal synchrony were found within and between
      association areas 5 and 7 and 18/19 and 21. Closely located cells or neuronal
      pools were also "closer" in time. The shortest mean time lag was found between
      cells within adjacent foci (1-2 mm) of areas 5 and 7 and was 12 +/- 11.2 (SE) ms,
      with more caudal neurons preceding the rostral ones in 70% of cases. In visual
      cortical fields, the time lag between areas 18/19 and 21 neurons was 27.6 +/- 36
      ms, between areas 17 and 21 was 36.2 +/- 47.8 ms, and between areas 18/19 and 17
      was 40 +/- 73 ms. In the majority of cases, neuronal firing in area 21 preceded
      that in areas 18/19. The longest time lags were found in distant recordings from
      visual and motor areas, with a mean of 124 +/- 86.8 ms, although in some cell
      groups the time intervals between neuronal firing in areas 18/19 or 21 and areas
      4 or 6 were as short as approximately 20 ms. 4. Similar time relations were found
      in those instances in which the unit firing of the same cortical neuron was used
      as reference in spike triggered averages and was related to the field potential
      recorded from an adjacent area before impaling a neuron and, thereafter, to
      membrane potential fluctuations after impaling the cell. 5. The PG reticular
      thalamic neurons reflected the slow cortical oscillation in 75% of multisite
      recordings.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714563
TI  - Presynaptic calcium-activated potassium channels and calcium channels at a
      crayfish neuromuscular junction.
AB  - 1. We used a two-microelectrode current clamp to investigate various
      characteristics of the Ca(2+)-activated K+ conductance [gK(Ca)] and Ca2+
      conductance (gCa), and transmitter release in presynaptic terminals of excitatory
      neuromuscular junctions in the crayfish walking leg. 2. Voltage-activated Na+
      conductances (gNa) and K+ conductances [gK(v)] were blocked with tetrodotoxin and
      3,4-diaminopyridine, respectively. Under these conditions, presynaptic
      depolarization produced by a first (conditioning) pulse admitted Ca2+ into the
      presynaptic terminals and activated gK(Ca), which modulated the amplitude of the
      depolarization produced by a second (test) pulse. The relative amount of gK(Ca)
      measured at the test pulse increased with increased magnitude or duration of the
      conditioning pulse. 3. A brief hyperpolarization immediately after a conditioning
      pulse substantially reduced gK(Ca). 4. gK(Ca) activation was blocked by funnel
      web spider toxin (a Ca2+ channel blocker) or by injection of the presynaptic
      terminal region with a calcium chelator, bis-(o-aminophenoxy)-N,N,N',N'
      tetraacetic acid (BAPTA). Under current-clamp conditions, gK(Ca) was not blocked
      by charybdotoxin or iberiotoxin [specific gK(Ca) blockers]. 5. When gK(Ca) was
      blocked or reduced, the amplitude of the depolarizing afterpotential of action
      potentials was increased. When gK(v) was blocked or reduced, the duration of
      action potentials was increased. 6. Intracellular injection of BAPTA into the
      presynaptic terminal region eliminated evoked neurotransmitter release before
      test pulse modulation was affected, suggesting that the K(Ca) channel had a
      greater sensitivity (greater affinity or lower stoichiometry) for Ca2+ than did
      the transmitter release machinery. BAPTA reduced neurotransmitter release by 66
      78%, but did not affect facilitation of neurotransmitter release. 7. When gNa,
      gK(v), and gK(Ca) were blocked, we detected a membrane depolarization produced by
      an increase in presynaptic gCa that was eliminated by 2 mM Cd2+ or 0 mM Ca2+.

PMID- 7714566
TI  - Modulation of epileptiform activity by metabotropic glutamate receptors in
      immature rat neocortex.
AB  - 1. Intracellular and extracellular recordings were obtained from neocortical
      brain slices of immature rats (postnatal days 9-16) maintained in vitro.
      Spontaneous and evoked epileptiform discharges (termed paroxysmal depolarizing
      shifts or PDSs) were recorded from upper cortical laminae (layers II-III) after
      exposure to the gamma-aminobuturic acid-A receptor antagonist, bicuculline
      methiodide. The effects of mGluR activation on PDS duration, spontaneous
      frequency, and threshold for evoking a PDS were determined. Putative mGluR
      agonists and antagonists also were tested. 2. Bath application of the mGluR
      agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD, 50-200 mM) elicited
      biphasic, time-dependent effects on evoked and spontaneous epileptiform
      discharges. At times early in drug wash-in, ACPD increased PDS duration and
      spontaneous PDS frequency. In > 60% of the slices, the spontaneous PDSs became
      regular. Subsequently, ACPD reduced PDS duration and increased the stimulus
      threshold for evoking a PDS, suggesting that the actions of ACPD were dose
      dependent. 3. Investigation of the concentration-dependence revealed that
      sustained low ACPD concentrations (5 microM) elicited only facilitatory actions,
      whereas higher concentrations were suppressive. These observations suggest the
      activation of different mGluR subtypes, which may be localized differentially at
      pre- and postsynaptic sites. 4. Bath application of the mGluR agonists, L-2-amino
      4-phosphonobutyrate or (2S,3S,4S)-alpha-(carboxycyclopropyl) glycine, produced
      only suppressive effects on epileptiform activity in the immature neocortex. L-2
      amino-3-phosphonopropionate was an ineffective antagonist of ACPD-mediated
      modulation of epileptiform activity. Application of the putative antagonist,
      alpha-methyl-4-carboxyphenylglycine (MCPG), failed to antagonize the biphasic
      actions of ACPD. MCPG had suppressive effects of epileptiform activity,
      suggesting activation of mGluRs by endogenous agonists. 5. Simultaneous
      recordings from deeper and upper cortical layers indicated that the initial
      negativity of both evoked and spontaneous PDSs began in deeper cortical layers
      under control conditions and in the presence of ACPD. Intracellular records from
      neurons in deeper layers displayed two distinct patterns of activity during mGluR
      activation. Most deep layer neurons received a barrage of excitatory postsynaptic
      potentials before a spontaneous PDS during ACPD application. A small population
      of neurons depolarized and entered a tonically firing mode, which was interrupted
      by spontaneous PDSs. Different neuronal populations, possible expressing
      different mGluR subtypes or coupling mechanisms, may play integral roles in the
      induction and generation of epileptiform activities. 6. Thapsigargin or
      dantrolene, agents thought to block release of Ca2+ from intracellular stores,
      were both applied for periods < or = min.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714567
TI  - Size and position invariance of neuronal responses in monkey inferotemporal
      cortex.
AB  - 1. Object vision is largely invariant to changes of retinal images of objects in
      size and position. To reveal neuronal mechanisms of this invariance, we recorded
      activities from single cells in the anterior part of the inferotemporal cortex
      (anterior IT), determined the critical features for the activation of individual
      cells, and examined the effects of changes in stimulus size and position on the
      responses. 2. Twenty-one percent of the anterior IT cells studied here responded
      to ranges of size > 4 octaves, whereas 43% responded to size ranges < 2 octaves.
      The optimal stimulus size, measured by the distance between the outer edges along
      the longest axis of the stimulus, ranged from 1.7 to 30 degrees. 3. The
      selectivity for shape was mostly preserved over the entire range of effective
      size and over the receptive field, whereas some subtle but statistically
      significant changes were observed in one half of the cells studied here. 4. The
      size-specific responses observed in 43% of the cells are consistent with recent
      psychophysical data that suggest that images of objects are stored in a size
      specific manner in the long-term memory. Both size-dependent and -independent
      processing of images may occur in anterior IT.

PMID- 7714568
TI  - Synchrony between single-unit activity and local field potentials in relation to
      periodicity coding in primary auditory cortex.
AB  - 1. We recorded responses from 136 single units and the corresponding local field
      potentials (LFPs) from the same electrode at 44 positions in the primary auditory
      cortex of 25 juvenile, ketamine-anesthetized cats in response to periodic click
      trains with click repetition rates between 1 and 32 Hz; to Poisson-distributed
      click trains with an average click rate of 4 Hz; and under spontaneous
      conditions. The aim of the study is to evaluate the synchrony between LFPs and
      single-unit responses, to compare their coding of periodic stimuli, and to
      elucidate mechanisms that limit this periodicity coding in primary auditory
      cortex. 2. We obtained averaged LFPs either as click-triggered averages, the
      classical evoked potentials, or as spike-triggered averages. We quantified LFPs
      by initial negative peak-to-positive peak amplitude. In addition, we obtained
      trigger events from negativegoing level crossings (at approximately 2 SD below
      the mean) of the 100-Hz low-pass electrode signal. We analyzed these LFP triggers
      similarly to single-unit spikes. 3. The average ratio of the LFP amplitude in
      response to the second click in a train and the LFP amplitude to the first click
      as a function of click rate was low-pass with a slight resonance at approximately
      10 Hz, and, above that frequency, decreasing with a slope of approximately 24
      dB/octave. We found the 50% point at approximately 16 Hz. In contrast, the LFP
      amplitude averaged over entire click trains was low-pass with a similar resonance
      but a high-frequency slope of 12 dB/octave and a 50% point at approximately 12
      Hz. 4. The LFP amplitude for click repetition rates between 5 and 11 Hz often
      showed augmentation, i.e., the amplitude increased in response to the first few
      clicks in the train and thereafter decreased. This augmentation was paralleled by
      an increase in the probability of firing in single units simultaneously recorded
      on the same electrode. 5. We calculated temporal modulation transfer functions
      (tMTFs) for single-unit spikes and for LFP triggers. They were typically bandpass
      with a best modulating frequency of 10 Hz and similar shape for both single-unit
      spikes and LFP triggers. The tMTF per click, obtained by dividing the tMTF by the
      number of clicks in the train, was low-pass with a 50% cutoff frequency at
      approximately Hz, similar to that for the average LFP amplitude. 6. the close
      similarity of the tMTFs for single-unit spikes and LFP triggers suggests that
      single-unit tMTFs can be predicted from LFP level crossings.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7714569
TI  - Postnatal development of pre- and postsynaptic GABAB-mediated inhibitions in the
      CA3 hippocampal region of the rat.
AB  - 1. Intracellular recordings were made from adult and neonatal rat hippocampal
      slices to study the postnatal development of GABAB-mediated inhibition in CA3
      pyramidal neurons. 2. In the presence of glutamatergic receptor antagonists,
      direct electrical stimulation of the interneurons induced a biphasic GABAA- and
      GABAB-mediated inhibitory postsynaptic potential in adult [postnatal day (P) 30
      P40] and young (P6-P8) CA3 pyramidal neurons. In contrast, in pups (P0-P3),
      electrical stimulation only induced a bicuculline-sensitive depolarizing GABAA
      synaptic potential. 3. The outward postsynaptic currents generated by bath
      applications of baclofen (30 microM, 30 s) at P3 (78 +/- 60 pA, mean +/- SE) were
      4 to 5 times smaller than those evoked between P6 (329 +/- 32 pA) and P30 (412 +/
      44 pA). At P0, baclofen failed to induce a postsynaptic current. 4. The outward
      currents generated by serotonin (50 microM, 30 s) and the A1 receptor agonist N
      cyclopentyladenosine (40 microM, 30 s) ranged between 0 and 50 pA at P3 and
      between 200 and 400 pA at P6 and P30 (holding potential = -60 +/- 2 mV). 5. In
      the presence of potassium channel blockers, the amplitude of calcium current
      elicited by a depolarizing voltage step command (1 s) from a holding potential of
      -60 mV to a test potential of 0 mV was 2 +/- 0.15 nA at P6 (n = 9) and 0.73 +/-
      0.14 nA at P3 (n = 8). Baclofen reversibly reduced the amplitude of calcium
      currents in young rats but not in pups. 6. Baclofen reversibly reduced the
      amplitude of the evoked GABAA-mediated and glutamatergic synaptic events at all
      developmental stages. These effects were dose dependent and antagonized by P
      alpha 3-aminopropyl-P-diethoxymethyl-phosphinic acid (CGP) 35348 (500 microM). 7.
      We conclude that postsynaptic GABAB-mediated inhibition is absent or minimal
      during the first postnatal days in the CA3 region. In contrast, presynaptic GABAB
      inhibition is present at birth. We discuss the mechanisms and physiological
      consequences of these observations.

PMID- 7714570
TI  - Inhibition in the superior olivary complex: pharmacological evidence from mouse
      brain slice.
AB  - 1. The effects of gamma-aminobutyric acid (GABA) and glycine and their respective
      antagonists were determined for neurons in the mouse superior olivary complex.
      Brain slices (400 microns) were cut in the frontal plane and maintained in an
      oxygenated saline solution for physiological recording. Recordings were made from
      neurons in the lateral superior olive (LSO) or medial nucleus of the trapezoid
      body (MNTB) with glass micropipettes filled with 4 M potassium acetate. 2.
      Ipsilateral and contralateral synaptic responses were elicited by applying
      current pulses to the trapezoid body through bipolar stimulating electrodes
      located at positions lateral and medial to the olivary complex. Both
      intracellular and extracellular recordings were studied before, during, and after
      application of drugs to the saline bath containing the tissue slice. 3.
      Intracellular recordings from 10 neurons in LSO showed that GABA (1-10 mM) caused
      a concentration-dependent drop in membrane resistance and either reduced or
      blocked postsynaptic excitatory responses. Similar effects were found in five
      cells tested with glycine (1-10 mM). Three neurons tested with both GABA and
      glycine were affected by both drugs. Extracellular spikes were blocked in 53 out
      of 67 LSO neurons tested with GABA and 29 out of 35 neurons tested with glycine.
      Seventeen out of 23 neurons tested with both GABA and glycine were affected by
      both. 4. GABA had a powerful blocking effect on extracellularly recorded action
      potentials evoked by current-pulse stimulation of the trapezoid body in seven LSO
      neurons tested after adding the glycine receptor antagonist, strychnine (1
      microM), to the bath. GABA also lowered the membrane resistance of one LSO neuron
      in which intracellular recordings were made in the presence of strychnine. 5.
      Neurons in MNTB also were affected by GABA and glycine but the proportion of
      sensitive cells was less than in LSO. GABA reduced membrane resistance in 6 out
      of 16 neurons and glycine produced a similar effect in 14 out of 26 neurons from
      which intracellular recordings were made. Six out of 14 neurons tested with GABA
      and glycine responded to both. Extracellular spikes were eliminated or reduced in
      amplitude by GABA in 15 out of 44 cells and by glycine in 40 out of 68 cells
      tested. Eleven out of 29 cells from which extracellular recordings were made were
      affected by both. 6. The glycine antagonist, strychnine (0.25 - 1.0 muM), blocked
      both ipsilateral and contralateral inhibitory postsynaptic potentials (IPSPs) in
      LSO.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714571
TI  - Distinct LTP induction mechanisms: contribution of NMDA receptors and voltage
      dependent calcium channels.
AB  - 1. Our results indicate that there are two distinct components of long-term
      potentiation (LTP) induced by the K+ channel blocker tetraethylammonium chloride
      (TEA) at synapses of hippocampal CA1 pyramidal neurons. Preincubation of
      hippocampal slices in the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2
      amino-5 phosphonovalerate (D,L-APV, 50 microM), reduced the magnitude of TEA LTP.
      In addition, the L-type voltage-dependent Ca2+ channel (VDCC) antagonist
      nifedipine (10 microM) attenuated TEA LTP. Only the combined application of D,L
      APV plus nifedipine blocked the induction of TEA LTP. 2. Occlusion experiments
      demonstrated that saturation of VDCC-dependent TEA LTP did not reduce or occlude
      NMDA-receptor-dependent TEA LTP. These results indicate that the mechanisms
      underlying VDCC and NMDA receptor components of TEA LTP are different and do not
      share a common saturable mechanism. 3. TEA LTP was strictly dependent on NMDA
      receptor activity in slices with CA3-CA1 connections severed (isolated CA1
      slices). In contrast to results obtained in slices with intact CA3-CA1
      connections, the NMDA receptor antagonists APV (50 microM) or MK-801 dizocilpine
      (10 microM) completely blocked TEA LTP in isolated CA1. Consistent with this
      observation, the properties of TEA LTP in isolated CA1 were very similar to other
      types of NMDA-receptor-dependent plasticity such as tetanus-induced LTP; TEA LTP
      required presynaptic stimulation, displayed pathway specificity, and was occluded
      by tetanus-induced LTP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714572
TI  - Neurons in monkey parietal area LIP are tuned for eye-movement parameters in
      three-dimensional space.
AB  - 1. A functional class of neurons in area LIP on the lateral bank of the
      intraparietal sulcus were shown previously (Gnadt and Andersen 1988) to be
      related to the metrics of saccadic eye movements. In this study, we tested LIP
      neurons at different depths with respect to the plane of fixation. 2. Sixty-one
      neurons were identified for their increased activity before saccadic eye
      movements. While holding the location of the target constant at the center of the
      frontoparallel (saccadic) response field, the neurons were tested systematically
      during eye movements to target positions proximal (near) to the plane of
      fixation, at the plane of fixation, and distal (far) to the plane of fixation. By
      necessity, the movements of these targets required a combination of saccadic and
      vergence movements. 3. Seventy-two percent of the neurons were found to change
      their activity as a function of target depth relative to the plane of fixation.
      The neurons had broad tuning curves for depth. Some cells preferred "near" target
      positions, some preferred "far" positions, and others responded best in the
      frontoparallel plane of fixation. 4. The location of a neuron's response field in
      the frontoparallel plane remained constant regardless of target depth. However,
      the magnitude of the neuron's response increased when the target was positioned
      at the preferred depth and it decreased for targets positioned at nonpreferred
      depths. This indicated that the neurons always were related to the same
      frontoparallel coordinates, but responded more vigorously when the target was
      positioned at its preferred depth. 5. The visual display apparatus allowed
      independent presentation of two stimulus cues for depth: binocular disparity and
      accommodative demand whereas other cues were held constant. For many neurons,
      either cue was sufficient to tune the activity in depth, though most neurons
      responded best for the geometrically appropriate combination of the two cues. 6.
      Comparison of the binocular tuning for depth with the individual monocular
      responses showed that the tuning for depth was not produced by simple linear
      combination of two monocular response fields. 7. We tested a subset of the
      neurons in a double-movement task that dissociated the retinal coordinates of the
      visual stimuli from the eye-movement coordinates of the second movement. These
      tests confirmed earlier findings that this functional class of neurons are active
      when the eye-movement coordinates matched the neurons' response field. It was not
      necessary for a visual stimulus to fall within the neurons' response field for
      them to become active.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714574
TI  - Properties of ATP-gated channels recorded from rat sympathetic neurons: voltage
      dependence and regulation by Zn2+ ions.
AB  - 1. I recorded ATP-gated channels from excised outside-out patches from rat
      sympathetic neurons. The channels had a unitary conductance of approximately 12
      pS at -80 mV, were activated only when ATP was present in the bath, and could be
      blocked by the P2-purinoceptor antagonist suramin. 2. The open probability of the
      channels showed a strong voltage dependence, increasing significantly with
      hyperpolarization. This suggests that whole cell rectification of currents evoked
      by P2X receptor activation is a result of channel voltage dependence and not of
      properties of ion permeation. 3. Low concentrations of extracellular Zn2+, which
      has previously been shown to potentiate whole cell ATP-evoked currents, increased
      the open probability of ATP-gated channels without altering the unitary
      conductance. 4. Zn2+ increased both the opening frequency and the burst duration
      of ATP-gated channels. The results are consistent with Zn2+ acting as an
      allosteric modulator of the P2X receptor in sympathetic neurons.

PMID- 7714573
TI  - Alterations of visual climbing fiber response properties in cat cerebellar
      flocculus after cerebral cortical lesions.
AB  - 1. In the anesthetized decorticate cat, we recorded complex spike (CS) activity
      together with concomitant simple spike (SS) activity of the cerebellar flocculus
      (FL) Purkinje cells that responded to large-field visual pattern movement. The
      cerebral cortical contributions to the visual response characteristics were
      investigated by comparing the present results with the previous results of the
      anesthetized normal cat. 2. The direction-selective characteristics of the CS
      responses at a low (2 degrees/s) stimulus velocity are well preserved after the
      decortication. As in the normal cat, the cells are divided into two major types:
      the horizontal type that prefers horizontal stimuli and the vertical type that
      prefers vertical stimuli. The CS rate of the former increases during stimuli
      directed contralaterally to the recording site and decreases during ipsiversive
      stimuli, whereas that of the latter increases during upward stimuli and decreases
      during downward stimuli. Reciprocal properties of the CS and SS responses also
      are preserved: when the CS rate increases, the SS rate decreases and vice versa.
      3. For both types, the CS modulation at high stimulus velocities is reduced after
      the decortication. The half-reduction of the average modulation occurs at
      approximately 100 degrees/s stimulus velocity compared with the modulation at 2
      degrees/s in the normal cat, whereas it occurs at a lower velocity approximately
      50 degrees/s in the decorticate cat. 4. For both types, the CS responses usually
      are driven through either eye in the normal cat. After the decortication, the CS
      modulation through the contralateral eye is reduced. 5. For both types, the
      receptive field of the ipsilateral eye extends into both visual hemifields in the
      normal cat. The CS responses through the contralateral visual hemifield are
      abolished, whereas those through the ipsilateral visual hemifield are preserved
      after the decortication. The CS modulation during stimuli restricted within a
      small central visual field (15 degrees x 15 degrees) projecting to the area
      centralis is prominent (approximately 70% of the full-screen response) in the
      normal cat and is sharply reduced (30%) after the decortication.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7714575
TI  - Passive and synaptic properties of hippocampal neurons grown in microcultures and
      in mass cultures.
AB  - 1. We used whole cell recordings to compare passive membrane properties and
      synaptic properties of postnatal rat hippocampal neurons grown for 7-15 days in
      either conventional mass cultures or on physically restricted microisland
      cultures. Despite matching microisland and mass culture cell across several
      variables, there were significant differences between neurons in the two groups
      regarding passive membrane characteristics and synaptic properties. 2.
      Microisland neurons displayed significantly faster charging of the membrane
      capacitance than mass culture counterparts matched with microisland neurons for
      age, somal diameter, and transmitter phenotype. When we used a two-compartment
      equivalent circuit model to quantify this result, microisland neurons displayed
      approximately half the distal capacitance of mass culture neurons. These data
      suggest that microisland neurons elaborate less extensive neuritic arborizations
      than mass culture neurons. 3. Evoked synaptic responses were enhanced on
      microislands compared with mass cultures. Excitatory and inhibitory autaptic
      currents were more frequent and displayed larger amplitudes on single-neuron
      microislands than in matched mass culture neurons. 4. In recordings from pairs of
      neurons in the two environments, we observed a significantly higher probability
      of obtaining a monosynaptic response on two-neuron microislands than in matched
      mass culture pairs (85% vs. 42%). Evoked excitatory postsynaptic currents were
      also significantly larger in the microisland environment, with evoked excitatory
      synaptic currents from two-neuron microislands exhibiting a mean amplitude 20
      fold larger than mass culture monosynaptic responses. 5. The differences in
      evoked synaptic responses were not reflected in differences in the amplitude or
      frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs).
      Analysis of mEPSC rise times, decay times, and peak amplitudes within individual
      cells suggests that electrotonic filtering is not an important contributor to the
      variability of peak amplitudes and decay times of synaptic currents in cells of
      either culture environment. However, composite data across neurons in both
      cultures reveal a significant correlation between mEPSC rise and decay times. 6.
      Out results suggest that the microisland preparation may be a useful tool for
      exploring factors that influence synapse formation and development. Additionally,
      the preparation is a particularly convenient model for the study of single-neuron
      mediated synaptic events.

PMID- 7714576
TI  - Biophysical and pharmacological characterization of inwardly rectifying K+
      currents in rat spinal cord astrocytes.
AB  - 1. Whole cell and cell-attached patch-clamp recordings were obtained from rat
      spinal cord astrocytes maintained in culture for 6-14 days. It was found that the
      resting conductance in these astrocytes is primarily due to inwardly rectifying
      K+ (Kir) channels. 2. Two types of astrocytic Kir channels were identified with
      single-channel conductances of approximately 28 and approximately 80 pS,
      respectively. Channels displayed some voltage dependence in their open
      probability, which was largest (0.8-0.9) near the K+ equilibrium potential (Ek)
      and decreased at more negative potentials. The resting potential closely followed
      Ek, so it can be assumed that Kir channels have a high open probability at the
      resting potential. 3. The conductance of inwardly rectifying K+ currents (Kir)
      depended strongly on [K+]o and was approximately proportional to the square-root
      of [K+]o. 4. Kir currents inactivated in a time- and voltage-dependent manner.
      The Na+ dependence of inactivation was studied with ion substitution experiments.
      Replacement of [Na+]o with choline or Li+ removed inactivation. This dependence
      of current inactivation on [Na+]o resembles the previously described block of Kir
      channels in other systems by [Na+]o. 5. Kir currents were also blocked in a dose
      dependent manner by Cs+ (Kd = 189 microM at -140 mV), Ba2+ (Kd = 3.5 microM), and
      tetraethylammonium (TEA; 90% block at 10 mM) but were insensitive to 4
      aminopyridine (4-AP; 5 mM). In the current-clamp mode, Ba2+ and TEA inhibition of
      Kir currents was associated with a marked depolarization, suggesting that Kir
      channel activity played a role in the establishment of the negative resting
      potential typical of astrocytes. 6. These biophysical features of astrocyte
      inwardly rectifying K+ channels are consistent with those properties required for
      their proposed involvement in [K+]o clearance: 1) high open probability at the
      resting potential, 2) increasing conductance with increasing [K+]o, and 3)
      rectification, e.g., channel closure, at positive potentials. It is proposed,
      therefore, that the dissipation of [K+]o following neuronal activity is mediated
      primarily by the activity of astrocytic Kir channels.

PMID- 7714577
TI  - Impairments of reaching movements in patients without proprioception. I. Spatial
      errors.
AB  - 1. This paper introduces a series of studies in which we analyze the impairments
      in a planar reaching task in human patients with severe proprioceptive deficits
      resulting from large-fiber sensory neuropathy. We studied three patients, all of
      whom showed absence of discriminative tactile sensation, position sense, and
      stretch reflexes in the upper extremities. Muscle strength was normal. We
      compared the reaching movements of the patients with those of normal control
      subjects. The purpose of this first paper was no characterize the spatial errors
      in these patients that result primarily from impairments in the planning and
      execution of movement rather than in feedback control. This was done by using a
      task in which visual feedback of errors during movement was prevented. 2.
      Subjects were instructed to move their hand from given starting positions of
      different targets on a horizontal digitizing tablet. Hand position and targets
      were displayed on a computer screen. Subjects could not see their hand, and the
      screen display of hand position was blanked at the signal to move. Thus visual
      feedback during movement could not be used to achieve accuracy. Movement paths
      were displayed as knowledge of results after each trial. 3. Compared with
      controls, the patients made large spatial errors in both movement direction and
      extent. Directional errors were evident from movement onset, suggesting that they
      resulted from improper planning. In addition, patients' hand paths showed large
      curves and secondary movements after initial stops. 4. The overall control
      strategy used by patients appeared the same as that used by controls. Hand
      trajectories were approximately bell shaped, and movement extent was controlled
      by scaling a trajectory waveform in amplitude and time. However, both control
      subjects and patients showed systematic errors in movement extent that depended
      on the direction of hand movement. In control subjects, these systematic
      dependencies of extent on direction were small, but in patients they produced
      large and prominent errors. Analysis of the hand trajectories revealed that
      errors were associated with differences in velocity and acceleration for
      movements in different directions. In an earlier study, we showed that in
      subjects with normal sensation that the dependence of acceleration and velocity
      on direction results from a failure to take the inertial properties of the limb
      into account in programming the initial trajectory. In control subjects, these
      differences in initial acceleration are partially compensated by direction
      dependent variations in movement time.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714578
TI  - Impairments of reaching movements in patients without proprioception. II. Effects
      of visual information on accuracy.
AB  - 1. The aim of this study was to determine how vision of a cursor indicating hand
      position on a computer screen or vision of the limb itself improves the accuracy
      of reaching movements in patients deprived of limb proprioception due to large
      fiber sensory neuropathy. In particular, we wished to ascertain the contribution
      of such information to improved planning rather than to feedback corrections. We
      analyzed spatial errors and hand trajectories of reaching movements made by
      subjects moving a hand-held cursor on a digitizing tablet while viewing targets
      displayed on a computer screen. The errors made when movements were performed
      without vision of their arm or of a screen cursor were compared with errors made
      when this information was available concurrently or prior to movement. 2. Both
      monitoring the screen cursor and seeing their limb in peripheral vision during
      movement improved the accuracy of the patients' movements. Improvements produced
      by seeing the cursor during movement are attributable simply to feedback
      corrections. However, because the target was not present in the actual workspace,
      improvements associated with vision of the limb must involve more complex
      corrective mechanisms. 3. Significant improvements in performance also occurred
      in trials without vision that were performed after viewing the limb at rest or
      during movements. In particular, prior vision of the limb in motion improved the
      ability of patients to vary the duration of movements in different directions so
      as to compensate for the inertial anisotropy of the limb. In addition, there were
      significant reductions in directional errors, path curvature, and late secondary
      movements. Comparable improvements in extent, direction, and curvature were
      produced when subjects could see the screen cursor during alternate movements to
      targets in different directions. 4. The effects of viewing the limb were
      transient and decayed during a period of minutes once vision of the limb was no
      longer available. 5. It is proposed that the improvements in performance produced
      after vision of the limb were mediated by the visual updating of internal models
      of the limb. Vision of the limb at rest may provide configuration information
      while vision of the limb in motion provides additional dynamic information.
      Vision of the cursor and the resulting ability to correct ongoing movements,
      however, is considered primarily to provide information about the dynamic
      properties of the limb and its response to neural commands.

PMID- 7714579
TI  - Functional anatomy of the mental representation of upper extremity movements in
      healthy subjects.
AB  - 1. Differences in the distribution of relative regional cerebral blood flow
      during motor imagery and execution of a joy-stick movement were investigated in
      six healthy volunteers with the use of positron emission tomography (PET). Both
      tasks were compared with a common baseline condition, motor preparation, and with
      each other. Data were analyzed for individual subjects and for the group, and
      areas of significant flow differences were related to anatomy by magnetic
      resonance imaging (MRI). 2. Imagining movements activated a number of frontal and
      parietal regions: medial and lateral premotor areas, anterior cingulate areas,
      ventral opercular premotor areas, and parts of superior and inferior parietal
      areas were all activated bilaterally when compared with preparation to move. 3.
      Execution of movements compared with imagining movements led to additional
      activations of the left primary sensorimotor cortex and adjacent areas: dorsal
      parts of the medial and lateral premotor cortex; adjacent cingulate areas; and
      rostral parts of the left superior parietal cortex. 4. Functionally distinct
      rostral and caudal parts of the posterior supplementary motor area (operationally
      defined as the SMA behind the coronal plane at the level of the anterior
      commissure) were identified. In the group, the rostral part of posterior SMA was
      activated by imagining movements, and a more caudoventral part was additionally
      activated during their execution. A similar dissociation was observed in the
      cingulate areas. Individual subjects showed that the precise site of these
      activations varied with the individual anatomy; however, a constant pattern of
      preferential activation within separate but adjacent gyri of the left hemisphere
      was preserved. 5. Functionally distinct regions were also observed in the
      parietal lobe: the caudal part of the superior parietal cortex [medial Brodmann
      area (BA) 7] was activated by imagining movements compared with preparing to
      execute them, whereas the more rostral parts of the superior parietal lobe (BA
      5), mainly on the left, were additionally activated by execution of the
      movements. 6. Within the operculum, three functionally distinct areas were
      observed: rostrally, prefrontal areas (BA 44 and 45) were more active during
      imagined than executed movements; a ventral premotor area (BA 6) was activated
      during both imagined and executed movements; and more caudally in the parietal
      lobe, an area was found that was mainly activated by execution presumably SII. 7.
      These data suggest that imagined movements can be viewed as a special form of
      "motor behavior' that, when compared with preparing to move, activate areas
      associated heretofore with selection of actions and multisensory
      integration.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714580
TI  - Mucosal inherent activity patterns in the rat: evidence from voltage-sensitive
      dyes.
AB  - 1. Fluorescence changes in the dye di-4-ANEPPS were monitored on the rat's nasal
      septum and medial surface of the turbinates in response to odorant stimuli. For
      each mucosal surface a 6.0 x 6.0-mm area was sampled at 100 contiguous sites with
      a 10 x 10 photodiode array. The odorants were propyl acetate, 2-propanol, citral,
      L-carvone and ethylacetoacetate, each presented at a low and high concentration.
      2. Like previous work using optical recording techniques and potential-sensitive
      dyes on the amphibian epithelium, the fluorescence signals elicited by odorant
      stimuli in the rat preparation were nearly identical in shape, time course, and
      response characteristics as the electroolfactogram (EOG). As with the EOG, a
      response could only be recorded in the presence of odorant stimuli (that is, no
      response was detected when nonodorized, humidified air was presented as the
      stimulus); the amplitude depended on odorant concentration, and the response was
      abolished both by ether and Triton X-100. 3. Although the entire expanse of each
      sampled tissue (i.e., septum and medial surface of the turbinates) responded to
      stimulation with each odorant, each stimulus induced a distinct spatial pattern
      of activity that was independent of odorant concentration and consistent from
      animal to animal. Furthermore, the spatial activity patterns recorded for the
      septum were mirror images of those recorded from the medial surface of the
      turbinates. 4. Formal statistical analysis of the loci of maximal activity or
      "hot spot" indicated highly significant effects of the odorants for both the
      septum and medial surface of the turbinates. 5. The results of these studies give
      further support to the hypothesis that odorant quality is encoded by differential
      spatial activity patterns in the olfactory epithelium that are characteristic of
      different odorants.

PMID- 7714581
TI  - Functional neural regeneration in the feeding system of Aplysia: behavioral
      recovery correlated with changes in buccal motor output.
AB  - 1. We tested for functional neural regeneration in the feeding system of Aplysia
      after bilateral transections or crushes of the cerebral-buccal connectives (CBCs)
      with the use of behavioral analyses and electrophysiological recordings. 2. Both
      types of lesion selectively abolished rhythmic consummatory behavior,
      dramatically increasing bite latency and interbite interval, and decreasing bite
      magnitude. Appetitive feeding behavior was not affected. 3. About 2 wk after CBC
      crush, bite latency, bite magnitude, and interbite interval began to recover, as
      rhythmic biting reappeared; complete recovery of rhythmic biting occurred within
      60 days. Rhythmic biting never recovered after transection of the CBCs. 4. The
      recovery of rhythmic biting was correlated with changes in buccal motor output,
      which were assessed with the use of in vivo recordings from buccal nerve 4 in
      freely moving Aplysia. Initially, some bursting in nerve 4 occurred without overt
      bites; with full recovery of biting, a 1:1 correspondence between bursts in nerve
      4 and overt bites returned. 5. CBC lesions caused a functional separation between
      biting and swallowing; at early times postlesion, subjects displayed apparently
      normal rhythmic swallowing even though rhythmic biting had been eliminated.
      However, there was a disruption of the 1:1 correspondence between nerve 4 bursts
      and swallows, which persisted until consummatory feeding fully recovered. 6.
      Transection of the CBCs in animals that had fully recovered from a previous CBC
      crush again abolished rhythmic biting, suggesting that the recovery of
      consummatory feeding behavior was due to functional neural regeneration of
      cerebral-buccal connections.

PMID- 7714582
TI  - Visualization of active neural circuitry in the spinal cord of intact zebrafish.
AB  - 1. One of the major obstacles in studying vertebrate neural networks is the
      difficulty in simultaneously monitoring activity in a population of neurons. To
      take advantage of the transparency of larval zebrafish, we used confocal
      microscopy to look into the spinal cord of immobilized fish to monitor neural
      responses during an escape behavior. 2. Populations of identified neurons were
      labeled with a calcium indicator and neural activity was monitored on a
      millisecond time scale. The calcium dependent nature of the fluorescent signals
      was confirmed by monitoring the accumulation, diffusion, and removal of calcium
      that was introduced by electrical and sensory stimulation. 3. Zebrafish, like
      most swimming vertebrates, have two major classes of motoneurons: large primary
      motoneurons thought to be used primarily for rapid movements and smaller
      secondary motoneurons implicated in slower movements. Our optical approach
      allowed us to ask how these groups of primary and secondary motoneurons respond
      during the escape behavior--one of the fastest and most forceful motor behaviors
      produced by vertebrates. 4. We demonstrate a previously unknown synchrony in the
      response of populations of primary and secondary motoneurons. This synchrony can
      account for the massive activation of the axial musculature during powerful
      escapes. Detection of this synchrony depended on the rapid in vivo imaging of
      activity in this neuronal population. This optical approach will allow functional
      studies of neuronal populations in the brain and spinal cord of normal and mutant
      lines of zebrafish.

PMID- 7714583
TI  - Statomotor system in the marine mollusk Clione limacina.
AB  - 1. In the marine mollusk Clione limacina the "statomotor system" (named by
      analogy with the oculomotor system) has been found. This system includes a muscle
      that is directly attached to the statocysts connecting them with each other and
      with the inner surface of the body. 2. The statocyst muscle consists of four
      electrically coupled, mononuclear cells. Statocyst muscle cells do not generate
      spike-like potentials but only excitatory junctional potentials. 3. The motor
      input to the statocyst muscle correlates with the activity of the locomotor
      generator. This suggests that in the soft-bodied Clione contraction of the
      statocyst muscle stabilizes the statocysts into a standard "working" position in
      relation to coordinates of the body. This statocyst stabilization is important
      for Clione's spatial orientation during swimming.

PMID- 7714584
TI  - Operant conditioning of H-reflex in freely moving rats.
AB  - 1. Primates can increase or decrease the spinal stretch reflex and its electrical
      analogue, the H-reflex (HR), in response to an operant conditioning task. This
      conditioning changes the spinal cord itself and thereby provides an experimental
      model for defining the processes and substrates of a learned change in behavior.
      Because the phenomenon has been demonstrated only in primates, its generality and
      theoretical implications remain unclear, and its experimental use is restricted
      by the difficulties of primate research. In response to these issues, the present
      study explored operant conditioning of the H-reflex in the rat. 2. Seventeen
      Sprague-Dawley rats implanted with chronic electromyographic (EMG) recording
      electrodes in one soleus muscle and nerve cuff stimulating electrodes on the
      posterior tibial nerve were rewarded (either with medial forebrain bundle
      stimulation or food) for increasing (HRup conditioning mode) or decreasing
      (HRdown conditioning mode) soleus H-reflex amplitude without change in background
      EMG or M response (direct muscle response) amplitude. 3. H-reflex amplitude
      changed appropriately over 3-4 wk. Under the HRup mode, it rose to an average of
      158 +/- 54% (mean +/- SD) of initial value, whereas under the HRdown mode it fell
      to an average of 67 +/- 11% of initial value. Background EMG and M response
      amplitude did not change. 4. Operant conditioning of the H-reflex in the rat
      appears similar in rate and final magnitude of change to that observed in the
      monkey.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714585
TI  - Suppression of the corrective response to loss of ground support by stimulation
      of extensor group I afferents.
AB  - 1. When a hind leg of a walking cat fails to contact the ground at the end of
      swing, the limb is rapidly lifted and replaced in an attempt to seek support. In
      this investigation we tested the hypothesis that one factor in the initiation of
      this corrective response is the absence of signals from the group I afferents of
      extensor muscles. 2. Experiments were performed on decerebrate cats walking on a
      treadmill. The corrective response to loss of ground support occurred when one
      hind leg stepped into a hole cut into the treadmill belt. Group I afferents in
      various extensor nerves were stimulated via implanted cuff electrodes when the
      foot entered the hole. 3. Stimulation of extensor group I afferents suppressed
      the corrective flexion response. Instead of a flexor burst being generated soon
      after the foot entered the hole, extensor activity was maintained for a period
      exceeding the duration of the stimulus trains. The onset of the corrective
      response occurred at a relatively fixed latency of 70 ms after the end of the
      short stimulus trains (200-400 ms) provided that the contralateral limb was still
      in stance phase. For longer stimulus trains (500-1,000 ms) that terminated during
      or just prior to the swing phase of the contralateral leg, the onset of
      ipsilateral flexor activity occurred only after the contralateral leg had
      regained support. 4. We conclude that the absence of signals from group I
      afferents when a foot fails to contact the ground allows the locomotor rhythm
      generator to re-initiate a flexor burst to produce the corrective
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714586
TI  - Direct demonstration of functional disconnection by anoxia of inhibitory
      interneurons from excitatory inputs in rat hippocampus.
AB  - 1. We studied the effects of anoxia on excitatory and inhibitory postsynaptic
      currents (EPSCs and IPSCs) evoked by electrical stimulation in the stratum
      radiatum in concomitantly recorded pyramidal cells and interneurons of the CA1
      region of rat hippocampal slices. We used the blind whole cell patch-clamp
      technique, and anoxia was induced by switching perfusion of the slice from
      oxygenated artificial cerebral spinal fluid (ACSF) to ACSF saturated with 95% N2
      5% CO2 for 4-6 min. 2. As in pyramidal neurons, anoxia induced in interneurons
      outward currents, during and shortly after the anoxic episode. Both currents
      were, however, significantly larger in interneurons than in pyramidal neurons. 3.
      EPSCs are more rapidly depressed by anoxia in interneurons than in simultaneously
      recorded pyramidal cells. 4. In pyramidal neurons, polysynaptic IPSCs (pIPSCs)
      evoked by conventional distant stimulation (> 1 mm) are more sensitive to anoxia
      then EPSCs. In contrast, in interneurons, anoxia blocks with a similar latency
      EPSCs and polysynaptic IPSCs. 5. To determine whether this block of pIPSCs in
      pyramidal cells is due to a shift in driving force or a change in conductance, we
      examined the current (I/V) relationships. The block by anoxia of pIPSCs is due to
      a reduction of IPSC conductance (> 98%) that occlude other events including the
      shift of IPSCs reversal potential (ECl).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714588
TI  - Nonstationary properties of the saccadic system: new constraints on models of
      saccadic control.
AB  - 1. We tested the predictions of two models of the saccadic burst generator by
      electrically stimulating sites in primate superior colliculus (SC) immediately
      following visually guided movements. 2. The amplitude and direction of stimulated
      saccades depend systematically on the amplitude and direction of preceding
      visually guided saccades, and that effect decays exponentially with a time
      constant of approximately 45 ms. The saccadic system, then, displays an amplitude
      dependent non-stationarity that follows an exponential time course during the
      intersaccadic interval (ISI). 3. These results are consistent with a variant of
      the eye displacement model proposed by Jurgens et al. but not with Robinson's
      classic model of the burst generator. Moreover, since all models of saccadic
      control must predict either stationary or nonstationary behavior during the ISI,
      these results provide a powerful new constraint on those models. 4. Finally, the
      success of the displacement model in accounting for our data suggests a new
      explanation for the results of colliding saccade experiments.

PMID- 7714587
TI  - Calcium-dependent inactivation of synaptic NMDA receptors in hippocampal neurons.
AB  - 1. We examined whether synaptically activated N-methyl-D-aspartate (NMDA)
      receptors are regulated by intracellular calcium in cultured hippocampal neurons
      by comparing excitatory postsynaptic currents (EPSCs) to the previously described
      calcium-dependent regulation of whole cell NMDA currents. Standard whole cell
      recording and fast application methods were used. 2. Low-frequency (0.2 Hz)
      stimulation of EPSCs in the presence of 2-amino-5-phosphonovalerate (AP5) evoked
      a constant amplitude alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) receptor-mediated EPSC. On removal of AP5 in Ca(2+)-containing solutions,
      the amplitude of the slow NMDA receptor-mediated EPSC decreased by approximately
      50% during the next 10 stimuli. The decrease in the EPSC was dependent on the
      extracellular calcium concentration and stimulus frequency, consistent with
      Ca(2+)-dependent desensitization/inactivation of postsynaptic NMDA receptors. A
      whole cell prepulse of NMDA (10 microM, 10 s) in Ca(2+)-containing solutions
      inhibited the slow EPSC to a similar degree. A series of slow EPSCs also produced
      Ca(2+)-dependent inactivation of whole cell NMDA currents evoked in low calcium
      solutions. 3. These results demonstrate that synaptic NMDA receptors are
      inactivated by intracellular calcium and that calcium entry through synaptically
      activated NMDA receptors is sufficient to provide feedback inhibition of the slow
      EPSC.

PMID- 7714589
TI  - Mechanisms of spontaneous calcium oscillations and action potentials in
      immortalized hypothalamic (GT1-7) neurons.
AB  - 1. Individual immortalized gonadotropin-releasing hormone (GnRH)-secreting
      hypothalamic (GT1-7) neurons in semiconfluent cultures showed spontaneous
      oscillations in intracellular Ca2+ concentration ([Ca2+]i) as measured by video
      fluorescence microscopy and fura-2. In parallel experiments, GT1-7 neurons also
      showed spontaneous bursts of action potentials that were recorded as action
      currents from intact cells. The bursts of action currents occurred in
      characteristic patterns, suggesting an underlying rhythmic oscillation in
      membrane potential. 2. Depolarization with increased extracellular K+ evoked a
      concentration-dependent increase in the frequency of Ca2+ oscillations or a
      sustained plateau of increased [Ca2+]i in GT1-7 neurons. Increased extracellular
      K+ (30 mM) caused an initial increase in the frequency of action currents, after
      which they were reversibly abolished. 3. The Ca2+ channel blockers Ni2+ and
      nimodipine abolished Ca2+ oscillations, whereas nifedipine, gadolinium, omega
      conotoxin and omega-agatoxin had no effect on Ca2+ oscillations. These results
      indicate that Ca2+ oscillations are generated by influx of Ca2+ through voltage
      gated Ca2+ channels that are not sensitive to nifedipine and are not N-type or P
      type channels. 4. Thapsigargin caused a small, transient rise in baseline [Ca2+]i
      but had no effect on Ca2+ oscillations. Caffeine and ryanodine had no effect on
      baseline [Ca2+]i or Ca2+ oscillations. These results indicate that the release of
      Ca2+ from inositol 1,4,5-trisphosphate (IP-3)-sensitive or caffeine sensitive
      intracellular stores does not play a major role in Ca2+ oscillations in GT1-7
      neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714590
TI  - Nonlinear behavior of muscle reflexes at the human ankle joint.
AB  - 1. Pulse inputs (similar to tendon jerks) were applied to the human ankle joint
      with the use of a hydraulic actuator. Inputs of only 1-2 degrees could elicit
      large responses (> 20% of maximum voluntary contraction). The magnitude of the
      response depended nonlinearly on a number of factors: the amplitude, direction,
      and duration of the pulse; the angle of the ankle; and the level of voluntary
      activation of the ankle muscles. 2. Pulses that flexed or extended the ankle
      could both produce reflex torques in the same direction (extensor torque).
      Although an extension of the ankle did not itself produce a response, it could
      affect the response to a subsequent flexion for up to 1 s. 3. The influence of
      random perturbations on the stretch reflex at the ankle was assessed. Responses
      to pulse displacements alone and to pulses superimposed on random perturbations
      were compared at the same level of voluntary activity. Reflex responses decreased
      in a graded manner with increasing amplitude or bandwidth of the random
      perturbations. 4. These results demonstrate that stretch reflexes can generate
      substantial torques, but in a highly nonlinear manner. In particular, passive
      joint movements markedly alter stretch reflex gain, and these changes must be
      considered in interpreting the functional significance of reflex actions.

PMID- 7714592
TI  - Activities of spinal neurons during brain stem-dependent fictive swimming in
      lamprey.
AB  - 1. We made intracellular microelectrode recordings of membrane potential from
      spinal neurons during fictive swimming elicited by brief electrical shocks to the
      spinal cord in a brain stem-spinal cord preparation of the adult silver lamprey
      (Ichthyomyzon unicuspis). 2. We characterized membrane potential activities
      recorded during brain stem-dependent fictive swimming in five spinal cell types:
      myotomal motoneurons, lateral interneurons (inhibitory neurons with ipsilateral
      descending axons), CC interneurons (neurons with contralateral and caudal
      projecting axons), edge cells (intraspinal stretch receptors), and dorsal cells
      (primary mechanosensory neurons with cell bodies in the spinal cord). The
      membrane potential activities were compared with data from previous reports
      recorded during fictive swimming in the isolated spinal cord with fictive
      swimming induced by superfusion with D-glutamate. 3. Compared with the same cell
      types recorded during D-glutamate-induced fictive swimming in brain stem
      dependent fictive swimming, the motoneurons and CC interneurons had significantly
      larger trough-to-peak amplitudes of membrane potential oscillations, whereas
      lateral interneurons were not significantly different in amplitude. The timings
      of the membrane potential oscillations and of cell spiking were not significantly
      different in the two preparations, with the exception that motoneurons in brain
      stem-dependent fictive swimming were significantly earlier by approximately 10%
      of a cycle. Edge cells had only weak or no oscillatory activities, and dorsal
      cells had no detectable input during brain stem-dependent fictive swimming. These
      findings are similar to those in D-glutamate-induced fictive swimming.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7714591
TI  - On the mechanism of modulation of transient outward current in cultured rat
      hippocampal neurons by di- and trivalent cations.
AB  - 1. The mechanisms of Zn2+ modulation of transient outward current (TOC) were
      studied in cultured rat hippocampal neurons, using the voltage-clamp technique.
      In the presence of micromolar concentrations of external Zn2+, the voltage
      dependence of activation and inactivation was shifted to more positive membrane
      potentials. The gating of TOC was unaltered by internal application of Zn2+. The
      effect of Zn2+ were not mimicked by external Ca2+, except at very high
      concentrations (> 10 mM). 2. The modulatory effects of external Zn2+ on TOC
      gating were not reproduced, antagonized, nor enhanced by lowering external ionic
      strength, indicating that modulation by Zn2+ does not occur via screening of bulk
      surface negative charge. 3. A range of other divalent and trivalent metal ions
      also was studied, and several were found to modulate the transient outward
      current when added to the extracellular medium. In particular, Pb2+, La3+, and
      Gd3+ were potent modulators, showing activity in the low micromolar range. Other
      metal ions were weaker modulators (e.g., Cd2+) or were without activity at the
      concentrations tested (Fe3+, Cu2+, Ni2+). 4. The same range of ions also was
      tested on the delayed rectifier K+ current in cultured rat hippocampal neurons.
      None of the ions studied had significant effects on delayed rectifier gating,
      although high (> or = 100 microM) concentrations of Pb2+ and La3+ reduced maximal
      current amplitude, suggesting the possibility of channel block.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7714593
TI  - Tactual discrimination of softness.
AB  - 1. We investigated the ability of humans to tactually discriminate the softness
      of objects, using novel elastic objects with deformable and rigid surfaces. For
      objects with deformable surfaces, we cast transparent rubber specimens with
      variable compliances. For objects with rigid surfaces ("spring cells") we
      fabricated telescoping hollow cylinders with the inner cylinder supported by
      several springs. To measure the human discriminability and to isolate the
      associated information-processing mechanisms, we performed psychophysical
      experiments under three conditions: 1) active touch with the normal finger, where
      both tactile and kinesthetic information was available to the subject: 2) active
      touch with local cutaneous anesthesia, so that only kinesthetic information was
      available; and 3) passive touch, where a computer-controlled mechanical
      stimulator brought down the compliant specimens onto the passive fingerpad of the
      subject, who therefore had only tactile information. 2. We first characterized
      the mechanical behavior of the human fingerpad and the test objects by
      determining the relationship between the depth and force of indentation during
      constant-velocity indentations by a rigid probe. The fingerpad exhibited a
      pronounced nonlinear behavior in the indentation depth versus force trace such
      that compliance, as indicated by the local slope of the trace, decreased with
      increases in indentation depth. The traces for all the rubber specimens were
      approximately linear, indicating a constant but distinct value of compliance for
      each specimen. The fingerpad was more compliant than each of the rubber
      specimens. 3. All the human subjects showed excellent softness discriminability
      in ranking the rubber specimens by active touch, and the subjective perception of
      softness correlated one-to-one with the objectively measured compliance. The
      ability of subjects to discriminate the compliance of spring cells was
      consistently poorer compared with that of the rubber specimens. 4. For pairwise
      discrimination of a selected set of rubber specimens, kinesthetic information
      alone was insufficient. However, tactile information alone was sufficient, even
      when the velocities and forces of specimen application were randomized. In
      contrast, for discriminating pairs of spring cells, tactile information alone was
      insufficient, and both tactile and kinesthetic information were found to be
      necessary. 5. The differences in the sufficiency of tactile information for the
      discrimination of the two types of objects can be explained by the mechanics of
      contact of the fingerpad and its effect on tactile information. For objects with
      deformable surfaces, the spatial pressure distribution within the contact region
      depends on both the force applied and the specimen compliance.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7714594
TI  - Surgical treatment of trigeminal schwannomas.
AB  - A total of 27 patients with trigeminal schwannoma were treated between 1982 and
      1992 at the Neurosurgery Department of Nordstadt Hospital. Twelve cases of
      solitary schwannoma without any family history or physical stigmata of
      neurofibromatosis were included and form the basis of this study. There were four
      women and eight men (mean age 44 years) in this series. Duration of symptoms
      ranged from 2 months to 6 years. The most frequent symptoms were either pain or
      numbness of the ipsilateral hemiface. The surgical approach was chosen depending
      on the tumor type. Tumors that belonged to Type A (five cases), which were
      predominantly in the middle fossa, were approached using a transsylvian method;
      Type B (one case), which presented predominantly in the cerebellopontine angle,
      was operated on via a retrosigmoid suboccipital craniectomy; Type C (five cases),
      which were dumbbell-shaped extending into both the middle and posterior fossa,
      were removed via a combined temporal craniotomy-presigmoidal method; and in Type
      D (one case), in which tumor was primarily extracranial with intracranial
      extension, an infratemporal extradural approach was undertaken. There was no
      operative mortality or long-term disability in this series. The follow-up period
      ranged from 12 to 60 months; during that time magnetic resonance imaging revealed
      tumor recurrence in two cases after 12 and 48 months, respectively, and these
      were excised again. An additional 178 cases collected from the world literature
      are also reviewed and analyzed.

PMID- 7714595
TI  - Comparison of conventional and skull base surgical approaches for the excision of
      trigeminal neurinomas.
AB  - Trigeminal neurinomas have traditionally been excised through conventional
      approaches. Because symptomatic tumor recurrence exceeds 50% after conventional
      procedures, the authors evaluated the use of skull base approaches to achieve
      complete resection and a lower rate of symptomatic recurrence. Comparisons of
      skull base with conventional approaches to trigeminal neurinomas have been
      limited to small series with short-term follow-up periods. The authors reviewed
      their experiences with conventional (frontotemporal transsylvian, subtemporal
      intradural, subtemporal-transtentorial, and suboccipital) and skull base
      (frontotemporal extradural-intradural, frontoorbitozygomatic, subtemporal
      anterior petrosal, and presigmoid posterior petrosal) surgical approaches for the
      excision of trigeminal neurinomas. In this paper they report the results of 15
      patients with trigeminal neurinoma who underwent 27 surgical procedures between
      1980 and 1990. Seventeen of the procedures used conventional and 10 used skull
      base approaches. All patients had tumors arising from Meckel's cave and the porus
      trigeminus either initially or on recurrence. Tumors located in the cavernous
      sinus recurred most frequently (83%); other tumors that recurred frequently were
      those located in Meckel's cave and the porus trigeminus (67%), and the posterior
      fossa (17%). The tumor extended into the anterolateral wall of the cavernous
      sinus in 38% of patients with cavernous sinus involvement. Tumor exposure and
      ease of dissection were superior with skull base approaches. Residual or
      recurrent tumors were found in 65% of patients following conventional approaches
      compared with 10% of patients following skull base approaches. Using skull base
      approaches, the surgeon was more accurate (90%) in estimating tumor excision than
      when using conventional approaches (43%). Perioperative complications were
      similar with both. The authors discuss the indications, advantages, and
      limitations of each approach. Based on anatomical considerations, they propose a
      strategy to best resect these tumors.

PMID- 7714596
TI  - Meningiomas arising from the falcotentorial junction. Clinical features,
      neuroimaging studies, and surgical treatment.
AB  - Meningiomas arising from the falcotentorial junction are extremely rare. The
      authors describe the clinical features, neuroimaging studies, and results of
      surgical treatment of meningiomas of the falcotentorial junction and clarify the
      characteristics of this lesion based on a review of the literature and seven
      patients treated at their institution. The most common symptoms resulted from
      intracranial hypertension. Upward-gaze palsy appeared in only one patient.
      Computerized tomography (CT) showed no specific findings, but there was no
      evidence of edema around the tumor. Magnetic resonance (MR) imaging revealed a
      round, smooth-bordered mass with a peritumoral rim, without edema, and showing
      marked contrast enhancement. The multiplanar capability of MR imaging delineated
      the relationship between the tumor and adjacent structures better than did CT.
      Detailed knowledge of the vascular structures, especially evidence of occlusion
      of the galenic venous system and the development of collateral venous channels,
      is critical for successful surgery; stereoscopic cerebral angiography is
      necessary to achieve this aim. The seven patients described developed five types
      of collateral venous channels: through the basal vein of Rosenthal to the
      petrosal vein, through the veins on the medial surface of the parietal and
      occipital lobes to the superior sagittal sinus, through superficial anastomotic
      veins, through veins of the posterior fossa to the transverse or straight sinus,
      and through the falcian veins to the superior sagittal sinus. The first three
      types mainly developed after occlusion of the galenic system. The tumors were
      removed through the occipital transtentorial approach with a large window at the
      posterior part of the falx. A favorable prognosis for patients undergoing
      surgical treatment of falcotentorial junction meningiomas can be expected if
      detailed neuroimaging studies and microsurgical techniques are used.

PMID- 7714597
TI  - Surgical treatment for cervical spondylitic myelopathy.
AB  - The long-term outcome of cervical spondylitic myelopathy after surgical treatment
      was retrospectively reviewed and critically evaluated in 100 patients with
      documented cervical myelopathy treated between 1978 and 1988 at our institution.
      Eighty-four patients were available for long-term study. The median duration of
      follow up was 7.35 years (range 3 to 9.5 years). There were 67 men and 17 women;
      their ages ranged from 27 to 86 years. The duration of preoperative symptoms
      ranged from 1 month to 10 years. Preoperative functional grade as evaluated with
      the Nurick Scale for the group was 2.1. Thirty-three patients with primarily
      anterior cord compression, one- or two-level disease, or a kyphotic neck
      deformity were treated by anterior decompression and fusion. Fifty-one patients
      with primarily posterior or cord compression and multiple-level disease were
      treated by posterior laminectomy. There was no difference in the preoperative
      functional grade in these two groups. The patients in the posterior treatment
      group were older (59 vs 55 years). There was no surgical mortality from the
      operative procedures; morbidity was 3.6%. Of the 33 patients undergoing anterior
      decompression and fusion, 24 showed immediate functional improvement and nine
      were unchanged. Of the 51 patients who underwent posterior laminectomy, 35
      demonstrated improvement, 11 were unchanged, and five were worse. Six patients,
      one in the anterior group and five in the posterior group, demonstrated early
      deterioration. Late deterioration occurred from 2 to 68 months postoperatively.
      Four (12%) patients who had undergone anterior procedures had additional
      posterior procedures, and seven (13.7%) patients who had undergone posterior
      procedures had additional decompressive surgery. The final functional status at
      last follow-up examination for the 33 patients in the anterior group was improved
      in 18, unchanged in nine, and deteriorated in six. Of the 51 patients who
      underwent posterior decompression, 19 benefited from the surgery, 13 were
      unchanged, and 19 were worse at last follow up than before their initial surgical
      procedure. Age, severity of disease, number of levels operated, and preoperative
      grade were not predictive of outcome. The only factor related to potential
      deterioration was the duration of symptoms preoperatively. The results indicate
      that with anterior or posterior decompression, long-term outcome is variable, and
      a subgroup of patients, even after adequate decompression and initial
      improvement, will have late functional deterioration.

PMID- 7714598
TI  - Symptomatic syringomyelia following surgery to treat retethering of
      lipomyelomeningoceles.
AB  - The authors report the cases of three children in whom symptomatic syringomyelia
      occurred de novo following an operation to relieve retethering of a previously
      treated lipomyelomeningocele. No patient had a Chiari malformation. In two cases,
      magnetic resonance imaging performed before the first operation did not show a
      syrinx. At the time of surgery to relieve retethering, it was discovered that one
      of these patients had a minor degree of terminal hydromyelia and the other had a
      prominent central canal within the conus medullaris. The third patient was
      initially studied by means of myelography, which gave no indication of a syrinx,
      and one was not found at the time of the surgery to release the retethering.
      Neurological deficits appeared abruptly within several months of operation in two
      children, and insidiously after 12 to 18 months in the other symptomatic
      individual. In all three cases, the syrinx involved the distal spinal cord
      adjacent to the site of the lipoma. Treatment consisted of syringosubarachnoid
      shunting, which arrested the progression of deficits but only partially reversed
      them. The details of each case are presented and the possible mechanism of syrinx
      formation discussed. Early recognition and treatment of this unusual but
      important problem are emphasized.

PMID- 7714599
TI  - An observational study of near-infrared spectroscopy during carotid
      endarterectomy.
AB  - Near-infrared spectroscopy was used to monitor changes in the cerebral
      oxygenation state in 13 patients during carotid endarterectomy. Variations in the
      levels of the chromophores (oxygenated hemoglobin (HbO2), deoxygenated hemoglobin
      (Hb), and oxidized cytochrome (CytO2)), and the total hemoglobin content (tHb)
      were compared with changes in middle cerebral artery flow velocity measured using
      transcranial Doppler ultrasonography. Of eight patients who showed a fall in flow
      velocity on application of the internal carotid artery cross-clamp, seven
      demonstrated a rapid and closely correlated fall in HbO2 signal, and an increase
      in Hb. Levels of CytO2 and tHb remained unchanged. During endarterectomy,
      recovery of the HbO2 and Hb levels toward preclamp baseline values occurred in
      three of these patients. Intraoperative shunts accelerated recovery of HbO2 and
      Hb signals in two of three individuals. Release of the internal carotid cross
      clamp resulted in a rapid increase in HbO2 and decrease in Hb signal in those
      patients in whom spontaneous recovery had not occurred; in five instances, a
      hyperemia evolved with raised flow velocity and HbO2 to above baseline values.
      Cross-clamping and subsequent reperfusion of the external carotid artery had no
      effect on any parameter measured. The authors conclude that near-infrared
      spectroscopy can register changes in cerebral oxygenation during carotid
      endarterectomy without significant contamination from extracranial tissues.

PMID- 7714600
TI  - Classification and regression trees (CART) for prediction of function at 1 year
      following head trauma.
AB  - A cohort of 514 hospitalized head-injury survivors was identified based on their
      injury and 448 (87%) of them were followed for 1 year. Comprehensive
      neurobehavioral testing was performed 1 month and 1 year after injury. The
      authors developed predictions of six neuropsychological and two psychosocial
      outcomes 1 year after head injury. Prediction trees are presented for verbal IQ,
      Halstead's Impairment Index, and work status at 1 year. Early predictors of
      neurobehavioral outcome in survivors are similar to previously reported
      predictors of mortality. Extent (both depth and length) of coma and age are the
      medical and demographic variables most predictive of late outcome. Adding 1-month
      scores substantially improves prediction of neuropsychological variables. The
      classification and regression tree is a useful technique for predicting long-term
      outcome in patients with head injury. The trees are simple enough to be used in a
      clinical setting and, especially with 1-month scores, predictions are accurate
      enough for clinical utility.

PMID- 7714601
TI  - Effects of coregistration of MR to CT images on MR stereotactic accuracy.
AB  - Coregistration of different modality imaging serves to increase the ease and
      accuracy of stereotactic procedures. In many cases, magnetic resonance (MR)
      stereotaxis is supplanting computerized tomography (CT). The advantages of
      increased anatomical detail and multiplanar imaging afforded by MR, however, are
      offset by its potential inaccuracy as well as the more cumbersome and less
      available nature of its hardware. A system has been developed by one of the
      authors by which MR imaging can be performed separately without a stereotactic
      fiducial headring. Then, immediately prior to surgery, a stereotactic CT scan is
      obtained and software is used to coregister CT and MR images anatomically by
      matching cranial landmarks in the two scans. The authors examined this system in
      six patients as well as with the use of a lucite phantom. After initially
      coregistering CT and MR images, six separate anatomical (for the patients) and
      eight artificial (for the phantom) targets were compared. With coregistration, in
      comparison to CT fiducial scans, errors in each axis are less than or equal to 1
      mm using the Cosman-Roberts-Wells system. In fact, the coregistered images are
      more accurate than MR fiducial images, in the anteroposterior (p = 0.001),
      lateral (p < 0.05), and vertical (p < 0.03) planes. Three-dimensional error was
      significantly less in the coregistered scans than the MR fiducial images (p <
      0.005). The coregistration procedure therefore not only increases the case of MR
      stereotaxis but also increases its accuracy.

PMID- 7714602
TI  - Endoscopic treatment of loculated hydrocephalus.
AB  - Loculated hydrocephalus remains a difficult neurosurgical problem and endoscopes
      designed to navigate through the ventricular system provide a new option for
      treatment. The authors review their experience, during the period March 1990 to
      June 1993, using a steerable fiberscope in 34 cases of loculated hydrocephalus to
      evaluate the efficacy of endoscopic cyst fenestration. The goals of treatment
      were to control hydrocephalus, simplify preexisting shunt systems, and reduce
      operative morbidity. Endoscopic cyst fenestrations reduced the shunt revision
      rate from 3.04 per year prior to endoscopy to 0.25 per year after the procedure,
      during a follow-up period ranging from 8 to 45 months, mean 26 months. However,
      eight patients (23.5%) required 14 repeat operations to control loculated
      hydrocephalus. After endoscopy, patients with multiloculated hydrocephalus had a
      nearly fivefold increased risk (relative risk 4.85) for shunt malfunction and
      more than a twofold increased risk (relative risk 2.43) for cyst recurrence
      versus patients with uniloculated hydrocephalus. Similarly, six (50%) of 12
      patients shunted prior to endoscopy required a repeat endoscopic procedure
      (relative risk 5.56). Although repeat endoscopic procedures may be required to
      control hydrocephalus, endoscopic cyst fenestration avoided placement of a shunt
      in seven (33%) of 21 patients with uniloculated hydrocephalus. One patient,
      encountered early in the authors' experience, required a craniotomy for
      fenestration of multiple ventricular cysts. Endoscopic complications included
      cerebrospinal fluid leakage in one case and ventriculitis in another. The authors
      conclude that endoscopic treatment of loculated hydrocephalus is a safe,
      minimally invasive technique that should be considered as the initial treatment
      option.

PMID- 7714603
TI  - Phase II trial of tirilazad in aneurysmal subarachnoid hemorrhage. A report of
      the Cooperative Aneurysm Study.
AB  - Tirilazad mesylate, a 21-aminosteroid free-radical scavenger, has been shown to
      ameliorate cerebral vasospasm and reduce infarct size in animal models of
      subarachnoid hemorrhage (SAH) and focal cerebral ischemia. In preparation for
      performing large-scale clinical trials in humans with aneurysmal SAH, the safety
      of varying doses of tirilazad was tested in a randomized, double-blind, vehicle
      controlled, sequential dose-escalation study at 12 Canadian neurosurgical
      centers. Two hundred forty-five patients with an aneurysmal SAH documented by
      angiography were enrolled in the study sequentially within 72 hours of
      hemorrhage. The patients were assigned to one of three dosage tiers: receiving
      0.6 mg/kg, 2 mg/kg, or 6 mg/kg tirilazad or vehicle per day intravenously in
      divided doses through Day 10 following the SAH. All patients also received oral
      nimodipine. No serious side effects of tirilazad treatment were identified at any
      of the three doses, despite close monitoring of hepatic and cardiac toxicity. A
      trend toward improvement in overall 3-month patient outcome was seen in the 2
      mg/kg per day tirilazad-treated group compared to the outcomes in the vehicle
      treated groups. We conclude that tirilazad mesylate is safe in SAH patients at
      doses up to 6 mg/kg per day for up to 10 days and is a promising drug for the
      treatment of patients with aneurysmal SAH.

PMID- 7714604
TI  - The poor prognosis of ruptured intracranial aneurysms of the posterior
      circulation.
AB  - The first 48 hours after aneurysmal subarachnoid hemorrhage are critical in
      determining final outcome. However, most patients who die during this initial
      period are not included in hospital-based studies. We investigated the occurrence
      of subarachnoid hemorrhage in a population-based study to evaluate possible
      predictors of poor outcome. All patients diagnosed with aneurysmal subarachnoid
      hemorrhage between 1955 and 1984 were selected for analysis of mortality in the
      first 30 days using the medical record-linkage system employed for
      epidemiological studies in Rochester, Minnesota. One hundred and thirty-six
      patients were identified. The mean age of these 99 women and 37 men was 55 years.
      Rates for survival to 48 hours were 32% for the 19 patients with posterior
      circulation aneurysms, 77% for the 87 patients with anterior circulation
      aneurysms, and 70% for the 30 patients with a presumed aneurysm (p < 0.0001).
      Rates for survival to 30 days were 11%, 57%, and 53%, respectively, in these
      three patient groups (p < 0.0001). Clinical grade on admission to the hospital,
      the main variable predictive of death within 48 hours, was significantly worse in
      patients with posterior circulation aneurysms than in others (p < 0.0001). The
      prognosis of ruptured posterior circulation aneurysms is poor. The high early
      mortality explains why posterior circulation aneurysms are uncommon in most
      clinical series of patients with subarachnoid hemorrhage. The management of
      incidentally discovered intact posterior circulation aneurysms may be influenced
      by these findings.

PMID- 7714605
TI  - Thrombosed growing giant aneurysms of the vertebral artery: growth mechanism and
      management.
AB  - Results in three patients with thrombosed giant aneurysms of the vertebral artery
      are reported. Each of the aneurysms presented as a mass lesion. On postcontrast
      computerized tomography and magnetic resonance imaging, each aneurysm
      demonstrated a patent lumen and intrathrombotic vascular channels. Two patients
      died and were autopsied, and the other patient was successfully treated.
      Pathological examination revealed that the aneurysms had staged clots, an open
      lumen, intrathrombotic channels with endothelial lining, and aneurysmal walls
      with intimal thickening. The authors suggest that the development of the
      intrathrombotic capillary channels may be an important factor in the growth of
      thrombosed giant aneurysm of the vertebral artery. Trapping of the aneurysm
      followed by aneurysmectomy appears to be the best treatment for this type of
      aneurysm.

PMID- 7714606
TI  - Pathological basis of spinal cord cavitation in syringomyelia: analysis of 105
      autopsy cases.
AB  - This report summarizes neuropathological, clinical, and general autopsy findings
      in 105 individuals with nonneoplastic syringomyelia. On the basis of detailed
      histological findings, three types of cavities were distinguished: 1) dilations
      of the central canal that communicated directly with the fourth ventricle (47
      cases); 2) noncommunicating (isolated) dilations of the central canal that arose
      below a syrinx-free segment of spinal cord (23 cases); and 3) extracanalicular
      syrinxes that originated in the spinal cord parenchyma and did not communicate
      with the central canal (35 cases). The incidence of communicating syrinxes in
      this study reflects an autopsy bias of morbid conditions such as severe birth
      defects. Communicating central canal syrinxes were found in association with
      hydrocephalus. The cavities were lined wholly or partially by ependyma and their
      overall length was influenced by age-related stenosis of the central canal. Non
      communicating central canal syrinxes arose at a variable distance below the
      fourth ventricle and were associated with disorders that presumably affect
      cerebrospinal fluid dynamics in the spinal subarachnoid space, such as the Chiari
      I malformation, basilar impression, and arachnoiditis. These cavities were
      usually defined rostrally and caudally by stenosis of the central canal and were
      much more likely than communicating syrinxes to dissect paracentrally into the
      parenchymal tissues. The paracentral dissections of the central canal syrinxes
      occurred preferentially into the posterolateral quadrant of the spinal cord.
      Extracanalicular (parenchymal) syrinxes were found typically in the watershed
      area of the spinal cord and were associated with conditions that injure spinal
      cord tissue (for example, trauma, infarction, and hemorrhage). A distinguishing
      feature of this type of cavitation was its frequent association with
      myelomalacia. Extracanalicular syrinxes and the paracentral dissections of
      central canal syrinxes were lined by glial or fibroglial tissue, ruptured
      frequently into the spinal subarachnoid space, and were characterized by the
      presence of central chromatolysis, neuronophagia, and Wallerian degeneration.
      Some lesions extended rostrally into the medulla or pons (syringobulbia).
      Although clinical information was incomplete, simple dilations of the central
      canal tended to produce nonspecific neurological findings such as spastic
      paraparesis, whereas deficits associated with extracanalicular syrinxes and the
      paracentral dissections of central canal syrinxes included segmental signs that
      were referable to affected nuclei and tracts. It is concluded that syringomyelia
      has several distinct cavitary patterns with different mechanisms of pathogenesis
      that probably determine the clinical features of the condition.

PMID- 7714607
TI  - Effects of acute ethanol intoxication on experimental brain injury in the rat:
      neurobehavioral and phosphorus-31 nuclear magnetic resonance spectroscopy
      studies.
AB  - Using the lateral fluid-percussion model of experimental brain injury in the rat,
      the authors investigated the effect of acute ethanol (EtOH) intoxication on
      cardiovascular changes, neurological motor deficits, brain bioenergetics, and
      mortality associated with traumatic brain injury. Two hours after gastric
      administration of EtOH (low dose in 20 animals, 1.5 g/kg; high dose in 28, 3.0
      g/kg) or saline (equal volume), animals were subjected to a fluid-percussion
      brain injury centered over the left parietal cortex. These injuries were of
      either moderate (X = 2.2 atm; 10 animals/treatment) or high severity (X = 3.0
      atm; 18 animals/saline, 10 animals/low-dose EtOH, and 18 animals/high-dose EtOH).
      Neurological motor function was evaluated daily over a 1-week period, while a
      subset of eight animals receiving high-dose EtOH and subjected to brain injury of
      high severity were monitored for 4 hours using phosphorus-31 nuclear magnetic
      resonance spectroscopy to determine intracellular pH, free magnesium, and brain
      cytosolic phosphorylation potential. A significant (p < 0.05) and prolonged (up
      to 1 hour) hypotension was observed in animals pretreated with either low- or
      high-dose EtOH. Neither low-dose (blood-EtOH concentration = 110 +/- 40 mg/dl)
      nor high-dose (blood-EtOH = 340 +/- 70 mg/dl) EtOH had any effect on survival or
      neurological motor function after moderate brain injury. Following severe brain
      injury, animals pretreated with high-dose (blood-EtOH concentration = 352 +/- 65
      mg/dl) EtOH showed a significantly increased mortality and markedly worsened
      neurological deficits at 24 hours postinjury. Following injury, free magnesium
      and cytosolic phosphorylation potential declined in both groups by approximately
      50% to 60%, with no significant differences between groups with respect to these
      variables. In contrast, brain intracellular pH in the EtOH-treated animals was
      consistently higher than in the control group after injury. These data suggest
      that prior exposure to EtOH, particularly at high concentrations, may have
      detrimental effects on neurobehavioral function and survival in the acute period
      (up to 24 hours) after severe brain injury, and may be associated with
      posttraumatic cerebral alkalosis.

PMID- 7714608
TI  - Effects of ethanol on respiratory function in traumatic brain injury.
AB  - It has been observed that traumatic brain injury (TBI) increases the
      susceptibility of the brain to subsequent hypoxia, and prolonged apnea occurs in
      ethanol (EtOH)-treated animals following brain injury. This investigation tests
      the hypothesis that EtOH suppresses ventilation and hypercapnic respiratory drive
      following TBI. Immature pigs were anesthetized with halothane and received a 2 to
      3 atm fluid-percussion brain injury. Respiratory parameters, including tidal
      volume, frequency, ventilation (VE), and arterial blood gases were measured on
      100% O2 and on 5% to 6% inspired CO2 in O2 prior to and at 10, 60, 120, and 180
      minutes after TBI. Hypercapnic response sensitivity (S) was measured as the
      change in VE per mm Hg increase in PaCO2. Intracranial pressure, mean arterial
      blood pressure, heart rate, brain temperature, glucose, and EtOH levels were also
      monitored. Three groups were studied: the first group of six received EtOH (3.5
      gm/kg, intragastrically) without brain injury; the second group of six received
      TBI without EtOH; the third group of eight received EtOH and TBI. Ethanol levels
      were 121 +/- 13 (standard error of the mean) mg/dl in the EtOH/TBI group (136 +/-
      25 in the EtOH group) at the time of injury, and 175 +/- 12 mg/dl in the EtOH/TBI
      group (200 +/- 20 mg/dl in the EtOH group) at 120 minutes after injury. The
      EtOH/TBI animals had significantly lower VE and S, and higher PaCO2 following
      brain injury (p < 0.05, repeated-measures analysis of variance). No significant
      differences were identified between groups for pH, PaCO2, intracranial pressure,
      heart rate, brain temperature, or glucose levels. Ethanol intoxication leads to
      significant impairment of respiratory control following traumatic brain injury
      and may contribute to brain injury in intoxicated trauma victims.

PMID- 7714609
TI  - Patterns of peptide-containing perivascular nerves in the circle of Willis: their
      absence in intracranial arteriovenous malformations.
AB  - Using standard immunohistochemical techniques and an improved procedure for whole
      mount vascular preparations, the authors describe the pattern and density of
      innervation of calcitonin gene-related peptide (CGRP)-like, neuropeptide Y (NPY)
      like and vasoactive intestinal polypeptide (VIP)-like immunoreactivity in major
      arteries of postmortem adult human circles of Willis. Calcitonin gene-related
      peptide-, NPY-, and VIP-LI exhibited a variety of varicose and nonvaricose single
      axons, and small and large perivascular nerve bundles. Although the density of
      innervation within each vascular segment was highly variable, the pattern of
      innervation for each neuropeptide observed was consistent throughout the circle
      of Willis. With the use of human and rat circles of Willis as positive control
      preparations, the lack of CGRP-LI, NPY-LI, and VIP-LI in vessel segments taken
      from five cases of intracranial arteriovenous malformations (AVMs) is also
      reported. It is concluded that adult human circles of Willis exhibit CGRP-LI, NPY
      LI, and VIP-LI perivascular nerves. In addition, intracranial AVMs do not possess
      these peptide-containing nerves that, in animals, normally mediate neurogenic
      control in the cerebrovasculature. It is hypothesized that this lack of
      innervation, and hence neurotrophic influence, may contribute to the development
      of AVMs.

PMID- 7714610
TI  - Protein kinase C and diacylglycerol content in basilar arteries during
      experimental cerebral vasospasm in the dog.
AB  - Sixteen dogs were entered into a study of the double subarachnoid hemorrhage
      (SAH) model of cerebral vasospasm. Six animals were sacrificed 72 hours after the
      first experimental SAH, and the remaining 10 animals were killed 72 hours after
      the second experimental SAH; ten additional animals served as controls. Basilar
      arteries were rapidly excised from the dogs and frozen. Multiple segments of the
      frozen arteries were analyzed independently for total protein and 1,2
      diacylglycerol (DAG) content, which averaged 3.17 (+/- 0.27 standard error of the
      mean; SEM) pmol DAG/microgram protein for all 25 arteries analyzed. A slight
      decreasing trend in DAG content relative to that of control vessels was found in
      vessels chronically constricted in situ by subarachnoid blood clot; however, this
      trend did not attain statistical significance. Two segments of the same vessels
      were assayed independently for protein kinase C (PKC) activity, which averaged
      1.21 (+/- 0.08 SEM) pmol phosphate incorporation per minute per microgram protein
      for all 24 arteries analyzed. A small decrease in PKC content was noted in
      vessels that experienced a single SAH; however, PKC returned to near control
      value in vessels subjected to double SAH. The ratio of particulate (membrane
      bound) to soluble PKC activity, an indicator of PKC translocation to the membrane
      and hence PKC activation, showed a small but statistically significant trend to
      increase with experimental SAH.

PMID- 7714611
TI  - The role of the epidermal growth factor receptor in human gliomas: I. The control
      of cell growth.
AB  - The epidermal growth factor receptor (EGFR) gene is amplified in over 40% of
      primary human glioblastomas and overexpressed in the majority. The authors'
      investigations demonstrate that the function of the EGFR in glioblastomas is
      distinct from that in other human cancers because it does not appear to mediate
      the primary growth-promoting effect of EGF. Findings show that the level of EGFR
      expression does not directly predict the growth response to EGF, with growth
      stimulated in some cells but inhibited in others when cells were cultured in
      plastic dishes. On the other hand, when human glioblastoma cells were placed in
      soft agar cultures, the cell line expressing the highest levels of the EGFR
      demonstrated considerable colony formation in response to EGF treatment. In
      addition, cell lines with the highest EGFR levels were also more resistant to the
      growth-suppressive effects of retinoic acid when maintained in soft agar. These
      observations suggest that even though the overexpression of the EGFR did not
      confer a distinct growth advantage to glioma cells cultured on flat culture
      dishes, the ability of these cells to maintain anchorage-independent growth in
      soft agar especially in response to EGF and retinoic acid is facilitated. Because
      anchorage-independent growth is the best in vitro correlate to tumorigenicity,
      amplification and overexpression of the EGFR in human glioblastoma cells may be
      in part responsible for the tumorigenic potential of these cells.

PMID- 7714612
TI  - The role of the epidermal growth factor receptor in human gliomas: II. The
      control of glial process extension and the expression of glial fibrillary acidic
      protein.
AB  - Our earlier investigations of the biology of the epidermal growth factor receptor
      (EGFR) in human gliomas demonstrated that the level of EGFR expression did not
      directly predict the glioma growth response to EGF, suggesting that the function
      of the EGFR in glioblastomas might not be limited to mediating the growth effects
      of EGF. We conducted the current studies to investigate the function(s) of the
      EGFR not related to growth control in human gliomas. These investigations show
      that the EGFR mediates the stimulative effects of EGF on glial process extension
      and glial fibrillary acidic protein (GFAP) expression. In addition, the level of
      EGFR expression correlates inversely with glioma cell responsiveness to
      differentiation promoting agents (for example, nerve growth factor and
      transforming growth factor-beta) that act through transmembrane tyrosine kinase
      receptors. Thus, glioma lines with a high level of EGFR expression (for example,
      T-98G cells) responded to fewer differentiation promoting factors than lines with
      a low level of EGFR expression (such as U-373MG cells). Our results suggest that
      the EGFR in gliomas may participate in mediating the process extension and GFAP
      stimulative effects of both EGF and other differentiation promoting agents. These
      properties represent components of the differentiated state in glia because their
      expression is stimulated by dibutyryl cyclic adenosine monophosphate in normal
      astrocytes. The involvement of the EGFR in the expression of these glial specific
      properties suggests that the EGFR may play an important role in glial
      differentiation.

PMID- 7714613
TI  - Vascular endothelial growth factor in human glioma cell lines: induced secretion
      by EGF, PDGF-BB, and bFGF.
AB  - Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is an
      endothelial cell-specific mitogen that is structurally related to platelet
      derived growth factor (PDGF). Vascular endothelial growth factor/vascular
      permeability factor induces angiogenesis in vivo and may play a critical role in
      tumor angiogenesis. Using immunohistochemical analysis, the authors demonstrated
      the presence of VEGF/VPF protein in surgical specimens of glioblastoma multiforme
      and cultured glioma cells. By means of an enzyme-linked immunosorbent assay
      (ELISA) of cell supernatants, the authors showed that VEGF/VPF is variably
      secreted by all nine cultured human malignant glioma cell lines (CH-235MG, D
      37MG, D-54MG, D-65MG, U-87MG, U-105MG, U-138MG, U-251MG, U-373MG) and by a single
      meningioma cell line (CH-157MN). An immunocytochemical survey of these cell lines
      revealed a cytoplasmic and cell-surface distribution of VEGF/VPF. In the U-105MG
      glioma cell line, VEGF/VPF secretion was induced with physiological
      concentrations of epidermal growth factor, PDGF-BB, or basic fibroblast growth
      factor, but not with PDGF-AA. Moreover, it was observed that activation of
      convergent growth factor signaling pathways led to increased glioma VEGF
      secretion. Similar results were obtained using these growth factor combinations
      in the D-54MG glioma cell line. The data obtained suggest a potential role for
      VEGF/VPF in tumor hypervascularity and peritumoral edema. These observations may
      lead to development of new therapeutic strategies.

PMID- 7714614
TI  - Expression of monocyte chemoattractant protein-1 in meningioma.
AB  - Monocyte chemoattractant protein-1 (MCP-1), purified from glioma cell line (U
      105MG) culture fluid, attracts monocytes but not neutrophils. Macrophage
      accumulation is one of the pathological features of meningioma. To investigate
      the mechanism of macrophage infiltration into meningioma, the expression and
      localization of MCP-1 in 16 cases of meningioma were studied using Northern blot
      analysis and immunohistochemistry. Seven of 16 meningiomas expressed MCP-1
      messenger ribonucleic acid and protein, and some degree of macrophage
      infiltration was seen in all 16 meningiomas. There was a relationship between MCP
      1 expression and the degree of macrophage infiltration; MCP-1 was strongly
      expressed in meningiomas with a high degree of macrophage infiltration. Sometimes
      the meningioma was accompanied by perifocal edema; a correlation between
      macrophage infiltration into brain tumors and perifocal edema has already been
      reported. It was found that the degree of MCP-1 expression is not correlated with
      the extent of perifocal edema. The authors' findings suggest that MCP-1 plays an
      important role in macrophage infiltration into meningioma.

PMID- 7714615
TI  - Endocrine and metabolic characteristics of polyoma large T transgenic mice that
      develop ACTH-producing pituitary tumors.
AB  - The authors have analyzed several endocrine and metabolic parameters in polyoma
      large T transgenic mice (PyLT-1) that develop adrenocorticotropic hormone (ACTH)
      immunoreactive pituitary tumors and in nontransgenic mice with tumor transplants.
      All clinically ill PyLT-1 mice (13 to 16 months of age) had pituitary
      macroadenomas and elevated plasma ACTH levels. Compared to PyLT-1 transgenic
      mice, the ACTH plasma concentrations in immunocompetent mice with transplant
      tumors were markedly raised. In these animals, a secondary effect of
      hypercorticotropism was documented by a moderate hyperglycemia. Furthermore, mice
      with transplant tumors had a pathological weight increase from the time the tumor
      was palpable. The present study supports and extends the authors' previous
      morphological documentation of the similarity between the ACTH-producing tumors
      in this mouse model and human Cushing's disease.

PMID- 7714616
TI  - Prolactin-producing pituitary tumor: resistance to dopamine agonist therapy. Case
      report.
AB  - A 14-year-old girl presented with a rapidly growing, invasive prolactin-producing
      pituitary tumor that failed to respond to dopamine agonist medication.
      Histological, immunocytochemical, and ultrastructural studies of the surgically
      removed tissue revealed a pleomorphic, chromophobic, or slightly acidophilic
      pituitary tumor that was immunoreactive for prolactin and that, according to
      electron microscopy, consisted of atypical lactotrophs showing no evidence of
      cell shrinkage. In situ hybridization demonstrated large amounts of prolactin
      messenger ribonucleic acid (mRNA), moderate amounts of estrogen receptor mRNA and
      dopamine (D2) receptor mRNA, and an absence of growth hormone mRNA in the tumor
      cells. Because D2 receptor mRNA was present in the tumor, causes other than D2
      receptor loss may have been responsible for the resistance of the lactotrophs to
      dopamine agonist administration.

PMID- 7714617
TI  - Multiple intraspinal low-grade astrocytomas mixed with lipoma (astrolipoma). Case
      report.
AB  - Multiple intraspinal low-grade astrocytomas without neurofibromatosis stigmata
      and low-grade astrocytoma with intermingled areas of adipose tissue have not been
      reported previously. The authors present the case of a 48-year-old woman with a 7
      month history of paraparesis. When she underwent surgery, multiple intraspinal
      mixed tumors made up of astrocytes mingled with adipose cells were found and
      excised. In this report, the authors refer to this tumor as an "astrolipoma" and
      discuss its characteristics.

PMID- 7714618
TI  - Tentorial meningioma and painful tic convulsif. Case report.
AB  - A case is presented of painful tic convulsif caused by a posterior fossa
      meningioma, with right trigeminal neuralgia and ipsilateral hemifacial spasm.
      Magnetic resonance images showed an ectatic right vertebral artery as a signal
      void area in the right cerebellopontine angle. At operation the tentorial
      meningioma, which did not compress either the fifth or the seventh cranial nerves
      directly, was totally removed via a suboccipital craniectomy. The patient had
      complete postoperative relief from the trigeminal neuralgia and her hemifacial
      spasm improved markedly with decreased frequency. From a pathophysiological
      standpoint, the painful tic convulsif in this case was probably produced by the
      tumor compressing and displacing the brainstem directly, with secondary
      neurovascular compression of the fifth and seventh nerves (the so-called "remote
      effect").

PMID- 7714619
TI  - Use of a new aneurysm clip with an inverted-spring mechanism to facilitate visual
      control during clip application. Technical note.
AB  - When operating on deep-seated cerebral aneurysms, the surgeon's visual control of
      clip application may be impaired by the clip holder unless adjacent structures
      are retracted. To improve visual control and reduce the necessity for retraction,
      the senior author (A.P.) developed a new concept: an aneurysm clip with an
      inverted-spring mechanism. The clip has two jaws that point away from the clip
      blades. The jaws of the clip holder articulate with the inner side of the clip
      jaws. By distending the jaws of the clip holder the blades of the clip are opened
      and vice versa. Thus the visual field increases while the clip application is
      proceeding. This instrumentation is useful, especially in cases of deep-seated
      aneurysms arising from the posterior circulation and in multiple aneurysms. In
      these latter cases even lesions located contralaterally could be reached with
      good visual control.

PMID- 7714620
TI  - Early history of neurosurgery in Manitoba: threads in the tapestry of world
      neurosurgery.
AB  - The author describes the history of neurosurgery in Manitoba, with particular
      emphasis on events that occurred after his arrival there in 1950. Highlights of
      global neurosurgery are spliced into the author's reminiscences to anchor the
      local history with that of neurosurgery as a whole.

PMID- 7714621
TI  - Endovascular alleviation of deficits.

PMID- 7714622
TI  - Melanotic neuroectodermal skull tumor.

PMID- 7714623
TI  - Solitary cysticercus granulomas.

PMID- 7714624
TI  - Surgery for lumbar spinal stenosis.

PMID- 7714625
TI  - Seasons, snow, and subarachnoid hemorrhage: lack of association in Rochester,
      Minnesota.

PMID- 7714626
TI  - Environmental turbulence. Impact on nurse performance.
AB  - Changes in the external regulatory environment have created turbulence in the
      internal hospital environment. Nursing administrators must create and maintain
      clinical environments that support practice; however, little is known about the
      effects of the dramatic changes in the healthcare environment on nurse
      performance. The author discusses a study that analyzed the effects of
      environmental turbulence on nurses' job performance. One characteristic of a
      turbulent environment, the number of admissions to/discharges from a unit in a 24
      hour period, had a negative impact on self-rated quality of performance. The
      findings give direction to nurse administrators regarding efforts and resources
      required to support nurse performance in the unstable and rapidly changing
      healthcare environment.

PMID- 7714627
TI  - A nursing research utilization strategy for staff nurses in the acute care
      setting.
AB  - The importance of research-based nursing practice is well recognized. However,
      typically, strategies to incorporate research findings into nursing practice have
      not been evaluated in terms of staff nurse outcomes. Thus, the purpose of this
      project was to evaluate the effectiveness of a research utilization strategy for
      staff nurses in the neonatal intensive care unit of a community teaching
      hospital. This project was intended to serve as a model for the incorporation of
      research findings into nursing practice on other nursing units in the acute care
      setting.

PMID- 7714628
TI  - A nursing-driven program to preserve and restore functional ability in
      hospitalized elderly patients.
AB  - The authors discuss the hazards of hospitalization for the elderly and the
      successful development and implementation of a six-bed module for geriatric
      assessment and rehabilitation in a community hospital. The project, unique
      because it was accomplished with minimal additional resources, included the
      purchase of clinical nurse specialist consultative services from another
      hospital. Although interdisciplinary in focus, the entire program was developed,
      implemented, autonomously managed, and evaluated by nursing staff.

PMID- 7714629
TI  - Heart Watch: national survey of continuous electrocardiographic monitoring in
      U.S. hospitals.
AB  - How is electrocardiographic monitoring being carried out in various settings?
      From results of a national survey, the authors describe unit characteristics and
      monitoring equipment and identify staff roles for carrying out related
      activities. Although much diversity was found, involvement in monitoring
      activities was highly consistent with the varying skill mixes in critical care,
      intermediate care, and "other" units responding. Data regarding the role of
      monitor technicians in this process raise questions about the viability of this
      role.

PMID- 7714630
TI  - Nurse executives: leadership motivation and leadership effectiveness.
AB  - In a mailed survey, chief nurse officers (N = 92) described their leadership
      motivation and leadership effectiveness. Leadership motivation scores depicted
      high needs for affiliation and moderate needs for power. Leadership effectiveness
      scores reported by chief nurse officer and chief executive officer (n = 59 pairs)
      were correlated positively. Significant predictors of leadership effectiveness
      were job satisfaction, education, professional recognition, and experience,
      respectively. Those motivated by socialized power needs were in the most complex
      hospitals, whereas those motivated by affiliation were in the least complex
      settings. Identification of the motivational needs of successful leaders and
      aspiring leaders is advocated to provide valid and reliable measures for use in
      assessment centers and to inform curricula.

PMID- 7714631
TI  - Measurement of patient outcomes: data availability and consistency across
      hospitals.
AB  - In a random sample of 20 hospitals, the availability and consistency of five
      patient outcome indicators were examined, including medication administration
      errors, patient falls, occurrence of new decubitus ulcers, nosocomial infections,
      and unplanned readmission to the hospital. The results indicate that information
      about only two outcome indicators--medication errors and patient falls--were
      collected consistently by the sampled hospitals. The findings are discussed in
      the context of implications for the study of patient outcomes research.

PMID- 7714632
TI  - Nursing research. A time for redirection.

PMID- 7714633
TI  - The three Rs.

PMID- 7714634
TI  - Breastfeeding.

PMID- 7714635
TI  - Genetics.

PMID- 7714636
TI  - Postpartum care center: follow-up care in a hospital-based clinic.
AB  - Because of ever-decreasing lengths of maternity stays and the emphasis on
      reducing health-care costs, there is a need for innovative, low-cost postpartum
      follow-up programs. The Postpartum Care Center, begun in 1991, is a model program
      that provides early postpartum assessment and support to mothers, infants, and
      their families for one third the cost of a home visit. This article reviews
      program development, description of services, and program outcomes.

PMID- 7714637
TI  - Getting enough: mothers' concerns about breastfeeding a preterm infant after
      discharge.
AB  - OBJECTIVE: To describe maternal concerns about breastfeeding a preterm infant in
      the postdischarge period and to delineate the strategies mothers used in managing
      these concerns. DESIGN: Naturalistic inquiry was used. SETTING: A semistructured
      interview was conducted with the mother in the home 1 month after discharge of
      the infant. PARTICIPANTS: Twenty mothers of preterm infants; the infants had been
      in a level 3 hospital nursery, and the mothers had received individualized
      breastfeeding support services in the hospital. MAIN OUTCOME MEASURES: Three
      categories of maternal concerns emerged from the data: adequate milk consumption
      by infants; milk composition; and problems with the mechanics of breastfeeding a
      preterm infant. Mothers identified strategies for these concerns. RESULTS: The
      mothers' main concern was whether infants consumed an adequate volume of milk by
      breastfeeding alone. Strategies for managing concerns about getting enough
      included using supplemental and complemental feeding, using ongoing cues to tell
      that the infant is getting enough, and persevering with breastfeeding.
      CONCLUSIONS: Mothers of preterm infants have unique concerns about breastfeeding
      in the postdischarge period and need individualized interventions.

PMID- 7714639
TI  - Follow-up of at-risk infants in the home setting: consultation model.
AB  - Infants are discharged from intensive care nurseries with varied risk levels and
      care needs that require a multilevel resource network. This article describes a
      consultation model that evolved from the collaborative effort of two regional
      hospitals with state funding support. A hospital-based clinical nurse specialist
      provides consultation to community health nurses and other providers of local
      follow-up services. Individualized mentoring, group educational sessions, and
      program consultation are adapted to the practice level and resource needs in each
      urban and rural community.

PMID- 7714638
TI  - HIV risk status and preventive behaviors among 17,619 women.
AB  - OBJECTIVES: To document the percentage of women at high risk for human
      immunodeficiency virus (HIV) infection among primary care clients, identify their
      most prevalent risk factors for HIV infection, and examine the relationships
      between risk status and preventive behaviors for HIV infection. DESIGN: Cross
      sectional. SETTING: Urban and nonurban primary care clinics. PARTICIPANTS: Female
      clients (N = 17,619) who voluntarily completed an HIV risk-assessment form. MAIN
      OUTCOME MEASURES: HIV risk status, condom use, and previous HIV testing. RESULTS:
      Using criteria from the Centers for Disease Control, the study found 14% of the
      sample to be at high risk for HIV infection. Prevalent risk factors were having
      sex with persons at high risk for AIDS, having sex with more than six persons in
      a year, and having more than two sexually transmitted diseases. Women at high
      risk were more likely to be older, urban, and black. Overall, rates of consistent
      condom use and HIV testing were low, 12% and 7%, respectively. Older women,
      coupled women, and women of color were least likely to use condoms consistently.
      Women at low risk were less likely to have had HIV tests. CONCLUSIONS: To prevent
      HIV infection, nursing interventions can target women of all ages, especially
      urban and black women. Nurses should use strategies and skills to promote condom
      use that are different from those they use to encourage HIV testing.

PMID- 7714640
TI  - Shortened hospital stay for low-birth-weight infants: nuts and bolts of a nursing
      intervention project.
AB  - Prolonged hospitalization of low-birth-weight (LBW) newborns places them at
      increased risk for a number of medical and psychosocial complications. A
      randomized trial of earlier hospital discharge with community-based nursing
      follow-up and intervention was performed. Community-based, in-home, public-health
      nursing and homemaker services were provided on an individualized basis according
      to assessed need. A significantly higher number of nurse home visits and
      telephone contacts were made to the intervention families. One of the most
      identified needs of families of LBW infants was assistance with breastfeeding.
      More than half of the early discharge families needed and received homemaker
      assistance during the first 8 weeks after the newborn's discharge from hospital.
      Results showed that a community-based program that provided individualized
      support and education for families of LBW infants was safe, cost-effective, and
      had a positive influence on the home environment.

PMID- 7714641
TI  - Creating a community of caring for families with special needs.
AB  - When parents are faced with the realization that their child has a disability or
      chronic illness, life is significantly changed. There can be tremendous emotional
      and economic stress as families seek diagnosis and treatment and face a
      bewildering search for appropriate programs. Uncertainty about the future and
      frustration with the present often leave caregivers overwhelmed. For these
      fragile families, a philosophy of family-centered care in their community is
      important. Ideally, this seamless system should offer continuity of care from
      birth through the childhood years and bridge medical, educational, and social
      services. Only in this environment can we assure that we are saving not only the
      infant but also the family.

PMID- 7714642
TI  - A home parenteral nutrition program for infants.
AB  - Infants with short bowel syndrome and other acquired or congenital
      gastrointestinal disorders are able to survive their neonatal period, in part,
      because of the use of parenteral nutrition (PN). An increasing number of these
      children are being cared for at home while receiving PN. This article reviews a
      home PN program for infants, including identification of patients, discharge
      planning, and outpatient care.

PMID- 7714643
TI  - Discharge planning and home care of the technology-dependent infant.
AB  - Technology-dependent infants are a medically complex, diverse group of
      individuals, many of whom can be cared for at home. Hospital discharge of any
      technology-dependent infant requires a multidisciplinary, comprehensive program
      of discharge planning and follow-up into the home. This article presents an
      overview of the technology-dependent infant population and a discussion of many
      of the pertinent issues for consideration during the discharge planning period
      and the transition from hospital to home.

PMID- 7714644
TI  - The art and science of home infant apnea monitoring in the 1990s.
AB  - The use of home apnea monitoring (HAM) continues as an accepted or recommended
      intervention for infants with certain signs and symptoms or medical diagnoses.
      Results of HAM in terms of case outcomes versus cost-effectiveness and efficacy
      remain matters of controversy in relation to the limited number of studies that
      show conflicting results. There are no studies that document the effectiveness of
      apnea monitoring. When an apnea monitor is prescribed, nursing can provide
      quality care through education and emotional support of families using HAM.

PMID- 7714645
TI  - Demodulation, predictive coding, and spatial vision.
AB  - We argue that some aspects of human spatial vision, particularly for textured
      patterns and scenes, can be described in terms of demodulation and predictive
      coding. Such nonlinear processes encode a pattern into local phasors that
      represent it completely as a modulation, in phase and amplitude, of a prediction
      associated with the image structure in some region by its predominant
      undulation(s). The demodulation representation of a pattern is an anisotropic,
      second-order form of predictive coding, and it offers a particularly efficient
      way to analyze and encode textures, as it identifies and exploits their
      underlying redundancies. In addition, self-consistent domains of redundancy in
      image structure provide a basis for image segmentation. We first provide an
      algorithm for computing the three elements of a complete demodulation transform
      of any image, and we illustrate such decompositions for both natural and
      synthetic images. We then present psychophysical evidence from spatial masking
      experiments, as well as illustrations of perceptual organization, that suggest a
      possible role for such underlying representations in human vision. In
      psychophysical experiments employing masks with more than two oriented Fourier
      components, we find that peaks of threshold elevation occur at locations in the
      Fourier plane remote from the orientations and frequencies of the actual mask
      components. Rather, as would occur from demodulation, these peaks in the
      frequency plane are related to the vector difference frequencies between the
      actual masking components and their spectral centers of mass. We offer a neural
      interpretation of demodulation coding, and finally we demonstrate a practical
      application of this process in a system for automatic visual recognition of
      personal identity by demodulation of a facial feature.

PMID- 7714646
TI  - Saccadic suppression of achromatic and chromatic responses measured by increment
      threshold spectral sensitivity.
AB  - We measured spectral-sensitivity functions during saccadic eye movement by the
      increment-threshold method to test whether saccades selectively suppressed
      achromatic or chromatic responses. A circular monochromatic test stimulus of 12
      deg diameter was presented for 10 ms on a 62 deg x 43 deg white background, and
      observations were made under three conditions: during fixation, during 6-deg
      saccades, and immediately after saccades. In two additional conditions the test
      stimulus was made to move during fixation and during 6-deg saccades at the same
      speed and in the same direction as the saccades. The during-fixation spectral
      sensitivity function was found to resemble the relative luminous efficiency V
      (lambda) function in shape except for the case of short wavelengths, whereas the
      during-saccade spectral-sensitivity function showed lower sensitivity for all
      wavelengths and had three prominent peaks at approximately 440, 530, and 600 nm.
      These characteristics did not depend on whether the stimulus was stationary or
      moving. These results indicated that saccadic suppression was greater for
      achromatic than for chromatic response. A possible suppression mechanism was
      discussed involving the magno and parvo pathways.

PMID- 7714647
TI  - Contrast gain control: a bilinear model for chromatic selectivity.
AB  - We report the results of psychophysical experiments on color contrast induction.
      In earlier work [Vision Res. 34, 3111 (1994)], we showed that modulating the
      spatial contrast of an annulus in time induces an apparent modulation of the
      contrast of a central disk, at isoluminance. Here we vary the chromatic
      properties of disk and annulus systematically in a study of the interactions
      among the luminance and the color-opponent channels. Results show that induced
      contrast depends linearly on both disk and annulus contrast, at low and moderate
      contrast levels. This dependence leads us to propose a bilinear model for color
      contrast gain control. The model predicts the magnitude and the chromatic
      properties of induced contrast. In agreement with experimental results, the model
      displays chromatic selectivity in contrast gain control and a negligible effect
      of contrast modulation at isoluminance on the appearance of achromatic contrast.
      We show that the bilinear model for chromatic selectivity may be realized as a
      feed-forward multiplicative gain control. Data collected at high contrast levels
      are fit by embellishing the model with saturating nonlinearities in the contrast
      gain control of each color channel.

PMID- 7714648
TI  - Effectiveness of pneumatic leg compression devices for the prevention of
      thromboembolic disease in orthopaedic trauma patients: a prospective, randomized
      study of compression alone versus no prophylaxis.
AB  - A prospective, randomized clinical trial in 304 orthopaedic trauma patients with
      hip and pelvic fractures was conducted to investigated the effectiveness of
      pneumatic sequential leg compression devices (PSLCDs) for the prevention of
      thromboembolic disease. The control group received no specific form of
      prophylaxis. Patients were followed by venous Doppler, duplex can, and
      ventilation perfusion lung scans. The study end-point was documented pulmonary
      embolism and/or deep vein thrombosis. The incidence of a venous thromboembolic
      event in the control group was 11% and in the experimental group 4%. This
      difference was statistically significant (p = 0.02). These patients were also
      stratified into hip and pelvic fracture groups. In the hip fracture patients, the
      control group had a thromboembolic event incidence of 12% and the experimental
      group 4%. This difference was also statistically significant (p = 0.03). In the
      pelvic fracture group there was a thromboembolic incidence of 11% in the
      controls, demonstrating this patient population to be at significant risk. In
      this group, the PSLCDs were not statistically shown to be effective. Pneumatic
      leg compression devices are effective in reducing the incidence of thromboembolic
      events in patients with hip fractures.

PMID- 7714649
TI  - A mechanical comparison of the dynamic compression plate, limited contact-dynamic
      compression plate, and point contact fixator.
AB  - Cortical bone porosis associated with the dynamic compression plate (DCP)
      prompted the development of the limited-contact dynamic compression plate (LC
      DCP) and the point-contact fixator (PC-Fix) to increase bone vascularity.
      However, the comparative fixation characteristics of the three designs are
      unknown. Transverse fractures were physiologically created in paired cadaveric
      sheep tibiae, which were plated before torsion testing and four-point bending to
      failure. The tibiae were grouped randomly and compared as follows: DCP versus LC
      DCP, DCP versus PC-Fix, and LC-DCP versus PC-Fix. Mean torque to failure
      demonstrated no significant difference between the three plates (p < 0.33). Mean
      bending stiffness, gap opening, and moment to failure also demonstrated no
      significant difference between the three designs with p < 0.29, < 0.13, and <
      0.16, respectively. The LC-DCP and PC-Fix have torsion and bending properties
      comparable with the DCP in the fixation of simple transverse diaphyseal
      fractures.

PMID- 7714650
TI  - Nonoperative treatment of Bennett's fracture: a 13-year follow-up.
AB  - We reviewed the treatment and results of 22 Bennett's fractures. Of these
      fractures, treated by closed reduction and plaster immobilization, 20 were
      available for follow-up. Eighteen patients had a subjectively satisfactory
      outcome, and seven had a radiographically confirmed arthrosis of the first
      carpometacarpal joint. Of these, two were severe and painfully impaired.
      Nonanatomic reduction was seen in six of the seven patients with arthrosis and is
      thus considered a prognostic factor of posttraumatic arthrosis.

PMID- 7714651
TI  - Intraoperative somatosensory evoked potential monitoring during acute pelvic
      fracture surgery.
AB  - Independent clinical neurological evaluation and intraoperative somatosensory
      evoked potential (SSEP) monitoring was performed on 30 vertically unstable
      hemipelvis fractures in 28 patients undergoing acute open reduction and internal
      fixation. Preoperative ipsilateral neurologic injury of the sciatic/lumbosacral
      plexus was noted in 15 of 30 fractures (50%). Significant unilateral SSEP changes
      occurred during manipulative reduction of two displaced sacroiliac joints and one
      sacral fracture. Because of the expeditious response of the surgical team, with
      release of traction/retraction, SSEP returned to baseline and no patient
      sustained an iatrogenic nerve injury or worsening of their preoperatie neurologic
      status. The incidence of postinjury lumbosacral plexopathy in unstable pelvic
      fractures is high (50%) when careful preoperative evaluation including SSEP is
      performed. The use of intraoperative SSEP monitoring is feasible in acute
      posterior pelvic fracture surgery and can help identify potential intraoperative
      iatrogenic lumbosacral neurological compromise.

PMID- 7714652
TI  - The retrograde medullary superior pubic ramus screw for the treatment of anterior
      pelvic ring disruptions: a new technique.
AB  - Retrograde medullary screws were used in 26 patients with unstable pelvic ring
      injuries to stabilize the superior public ramus fractures. The posterior pelvic
      ring fractures and dislocations were fixed with iliosacral screws. The retrograde
      screws were inserted after closed manipulative reductions of the superior pubic
      ramus fractures in 15 patients and after open reduction in nine patients. We were
      unable to insert the screw in two patients due to anatomical variations. One
      screw was misplaced superior to the pubic ramus and noted only on the
      postoperative computed tomography scan. Another patient experienced symptomatic
      screw disengagement that required reoperation. All fractures healed and no
      infections developed. Blood loss was minimal for the percutaneous procedures. The
      technique provides stability to the anterior pelvic ring without the need for
      extensile surgical exposures. The complications of both anterior pelvic external
      fixation and plating are avoided, yet this technique has its own potential
      problems. The procedure is described in detail, and the early results and
      complications are documented in our first 26 patients.

PMID- 7714653
TI  - A biomechanical evaluation of the long stem intramedullary hip screw.
AB  - Despite the advantages associated with short-stem intramedullary hip screw
      devices for the treatment of intertrochanteric fractures, recent reports have
      shown an increased incidence of femoral shaft fractures after their insertion.
      These findings led to the hypothesis that an intramedullary hip screw with a
      longer stem may more effectively redistribute loads to the distal end of the
      femoral shaft, where they may be more readily absorbed by the increased bony
      cross-sectional area. To characterize the load patterns of a long-stem device in
      the femur, 10 fresh-frozen adult femurs were instrumented with unidirectional
      strain gauges. A total of eight strain gauges were placed in the direction of
      principal femoral strains on the medial and lateral surfaces of each femur. Each
      femur was held in a steel vice at 15 degrees of adduction in the coronal plane
      and vertical in the sagittal plane. The femurs were then subjected to
      successively increasing vertically applied compressive loads from 0 N to 1,400 N
      at 200-N increments using a servohydraulic testing machine. Strain values were
      recorded at each load after a 5-min equilibration period. Each femur was tested
      under five conditions: (a) intact, (b) after insertion of the long-stem
      intramedullary hip screw device, (c) with an experimentally created two-part
      fracture, (d) with a stable four-part fracture, and (e) with an unstable four
      part fracture with the posteromedial fragment removed. Half the femurs were
      randomly assigned to have two distal interlocking screws placed before fracture.
      The remaining half were loaded without distal interlocking screws.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7714654
TI  - Failure of the gamma nail in a highly unstable proximal femur fracture: report of
      four cases encountered in The Netherlands.
AB  - Static forces of body weight and dynamic forces induced by walking are a
      challenge toward lasting fixation devices in the case of unstable
      peritrochanteric fractures. Experiences with the newly developed gamma nail
      internal fixation technique are promising. The fixation is stable, complication
      rates are low, and fractures of the gamma nail itself have not been reported
      before. From the Dutch experience, the authors describe the four known cases of
      implant failure. In cases in which the process of bony healing is disturbed, the
      dynamic stresses during ambulation become large enough to cause metal fatigue
      fractures. In these cases adjuvant and appropriate measures should be undertaken.

PMID- 7714655
TI  - Intramedullary nailing of acute femoral shaft fractures using manual traction
      without a fracture table.
AB  - Intramedullary (IM) nails were prospectively placed in 32 consecutive femoral
      shaft fractures without the use of a fracture table. All fractures were reduced
      using manual traction. Pathologic and nonacute fractures and those requiring a
      reconstruction nail were excluded. The results are compared with results of two
      prior study groups from this institution that underwent IM nailing with or
      without a fracture table using a femoral distractor. Ten patients had unstable
      spine or pelvis fractures. Four nailings followed exploratory laparotomy. Twelve
      patients underwent two or more procedures on the lower extremities under the same
      preparation and drape. Six fractures were open. Sixty-seven percent of results
      were anatomic, 27% had < 5 mm lengthening/shortening or < 5 degree varus/valgus,
      and 7% had > 5 mm lengthening/shortening or > 5 degree varus/valgus. Average
      operative time was 95 min. No complications occurred that were attributable to
      the technique. Compared with the prior study groups, no statistical difference in
      the fracture types or results was found. However, operative time was
      significantly less in the manual traction group (p < .05). We feel that this
      technique is a safe, simple, and effective alternative to using a fracture table.
      The technique is especially useful in the polytrauma patient, significantly
      decreasing anesthetic time.

PMID- 7714656
TI  - Anatomy of the medial distal femur: a study of the adductor hiatus.
AB  - The proximity of the vascular structures traversing the adductor hiatus in the
      medial distal femur is a potential concern for the surgeon. The distance from the
      adductor tubercle to the adductor hiatus was measured in both lower extremities
      in 24 skeletally mature cadavers. This distance ranged from 8.0 to 13.5 cm (mean
      10.0). The area up to 8 cm proximal to the adductor tubercle, anterior to the
      medial intermuscular septum, appears to be a safe interval for avoiding vascular
      structures with percutaneous or limited open surgeries of the medial aspect of
      the distal femur.

PMID- 7714657
TI  - Nonreamed nailing of tibial diaphyseal fractures in blunt polytrauma patients.
AB  - The efficacy of nonreamed nailing as the treatment of choice of unstable blunt
      tibial diaphyseal fractures was studied. From March 1, 1990, through August 31,
      1991, 72 patients with 74 fractures that required fixation were treated. One
      patient died and six were lost to follow-up, leaving 65 patients with 67
      fractures. Follow-up averaged 21 months (range 5-43). Fisher's exact and logistic
      regression analyses were used to compare grades of open fractures, comminution as
      classified by Winquist, and dynamic and static nailings. The failure rates of 51
      titanium and 16 stainless steel nails were compared. Times to union were compared
      by the log rank statistic method. The average time to union was 32 weeks with 26
      (39%) additional operations required to achieve union; 13 dynamizations (12
      successful), 12 exchange nailings (11 successful), and one plate and bone graft.
      The rate of reconstructive procedures to achieve union was a more sensitive
      indicator of difficulties achieving union than was time to union. Reoperation
      rates were 33% for closed or grade I and II fractures compared with 46% for grade
      III fractures (NS). Among closed grade I and II static versus dynamic nailing,
      times to union were 36 versus 25 weeks (p < 0.01), and the reoperation rates were
      44% versus 13% (p < 0.04). Winquist I and II fractures required a 24% reoperation
      rate versus 53% for grade III and IV and segmental fractures (p < 0.01). Static
      locked fractures required a 48% reoperation rate versus 12% for dynamic locked
      fractures (p < 0.01). A logistic regression analysis demonstrated that locking
      mode was the most important factor in determining reoperation rates. Fifteen
      additional reoperations for infection, broken or painful implants, or to remodel
      bones that united with an incomplete circumference of cortex were performed. With
      an additional 12 elective nail removals, the total reoperations numbered 53
      (79%). Titanium alloy nails had a 2% failure rate versus 25% for stainless steel
      nails (p < 0.01). Two of 28 (7%) grade III fractures became infected. All
      fractures united within 10 degrees of normal alignment and 1 cm of length. Nine
      (13%) united with an incomplete cortical circumference, refractory to
      dynamization and full weight bearing. Thirteen of the 58 (22%) fractures
      available for an evaluation of ankle motion were symptomatic, with < 10 degrees
      of dorsiflexion.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714658
TI  - Articulated external fixation of pilon fractures: the effects on ankle joint
      kinematics.
AB  - The effect of the Orthofix articulated ankle external fixator on ankle and
      subtalar joint kinematics and fracture fragment motion was investigated in fresh
      cadaver specimens using biplanar radiographic analysis. The kinematic testing was
      performed for the normal ankle (i.e., no fixation) and for three alternate
      fixator hinge orientations. The fixator applications simulated a horizontal ankle
      axis (the current clinically preferred orientation), an axis coincident with a
      previously defined approximate ankle axis, and an axis located using a mechanical
      axis finder. The horizontal fixator application significantly disturbed normal
      ankle kinematics. Aligning the fixator hinge with an approximate ankle axis
      caused significant distortion of motion about only two of six possible rotational
      axes. Aligning the fixator hinge with the (specimen-specific) ankle axis
      determined by the axis finder most closely matched the motion of the normal
      ankle. For pilon fractures simulated by a transverse osteotomy, there appeared to
      be no physiologically significant fracture fragment motions, regardless of
      fracture stability or fixator orientation.

PMID- 7714659
TI  - A comparison of malreduction after plate and intramedullary nail fixation of
      forearm fractures.
AB  - A study was performed to compare the degree of malreduction after intramedullary
      nail and plate fixation of the forearm and to determine if the degree of
      malreduction was clinically significant. Eight matched pairs of forearms,
      including the wrist and elbow joints, were harvested from cadaver upper
      extremities. The forearms were put through a full range of motion, and
      physiological loads were applied to simulate those during normal use.
      Standardized anteroposterior and lateral radiographs of each forearm were
      obtained with the specimen intact, and after an osteotomy and internal fixation
      of one bone, both bones, and with gap at the osteotomy sites. In each forearm
      pair, plating was randomly performed in one specimen and intramedullary nailing
      was performed in the matching contralateral specimen. Forearm architecture was
      assessed by quantification of the magnitude and location of maximum radial bow
      and radial angulation. In this study, plate fixation was superior to nail
      stabilization in restoration of the normal radial architecture. Plating did not
      change any of the radiographic indices (magnitude and location of maximum radial
      bow and radial angulation) at any stage of testing. None of the radiographic
      indices was changed by nailing of only one of the forearm bones. The magnitude of
      maximum radial bow and the radial angulation were changed by nailing both forearm
      bones after osteotomy and both forearm bones with a gap (p < 0.05). Despite this,
      both techniques were well within the limits of what is radiographically
      acceptable for reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714660
TI  - An investigation of the bending stiffness of and the plane stresses generated by
      a flanged external fixator pin.
AB  - In an attempt to reduce pin loosening, a flanged external fixator pin has been
      designed and its bending stiffness has been compared with that of a standard pin.
      The pins were inserted into pilot holes previously drilled into a piece of teak
      hardwood. Loads of different magnitudes were applied at a fixed moment arm and
      force-deflection curves were obtained. Thereafter, percentage stiffness increase
      was calculated for each pilot hole size. The results show that the addition of a
      collar to the external fixator pin increases its stiffness and its ability to
      resist bending forces. In a parallel study, the stresses generated at the pin
      bone interface by this pin and a standard pin were compared using finite element
      analysis techniques. The results show that the flange significantly reduced the
      stresses generated at the pin-bone interface. In addition, stresses were
      dissipated over a wider area.

PMID- 7714661
TI  - A new plastic evacuated tube with plasma separator.
AB  - A new plastic-walled, evacuated blood collection tube (Terumo Venoject II) with
      plasma separator was evaluated for characteristics related to the use of plastic
      in place of glass. Plastic tubes were highly resistant to breakage through
      handling mishaps or failure during centrifugation. Higher centrifugation speed
      (13,600g) was well tolerated, and centrifugation times as short as 3 minutes at
      13,600g effectively cleared plasma of cellular components, at high plasma yield.
      Plastic tubes were nearly completely combustible under incineration conditions
      commonly used for medical waste, and plastic tubes effectively retained vacuum
      during the typical shelf life of evacuated blood collection tubes. Collection of
      carbamezepine specimens in plastic tubes decreased levels an average of 6.8%
      compared to a heparinized glass tube control under conditions approximating
      routine use; levels of other drugs (phenytoin, phenobarbital, valproic acid,
      theophylline, and cyclosporine) were less significantly affected. This modest
      decrease appeared to result from a combination of an immediate interaction with
      the plastic surface of the tubes and a time-dependent interaction with the olefin
      based separator. Modest but clear benefits, including reduction in specimen
      breakage, reduced centrifugation time and reduced solid waste after incineration
      derive from the use of plastic in place of glass in evacuated blood collection
      tubes.

PMID- 7714662
TI  - Reassessment of the two-site enzyme immunoassay for human epidermal growth factor
      (hEGF) and measurement of immunoreactive hEGF in human sera and urine.
AB  - We reassessed the enzyme immunoassay (EIA) system for hEGF previously developed
      by our laboratory (Clin Chim Acta 156:51-60, 1985), since it appeared that the
      reported EIA system detected not only hEGF but also pS2 protein owing to minor
      contamination by pS2 protein in the hEGF sample used for immunization. In this
      study, we purified the hEGF sample using Benzamidine-Sepharose 6B column
      chromatography as a critical step for purification and newly developed an EIA
      system with specificity for hEGF. We also measured the hEGF level in serum,
      plasma, and urine from normal subjects by our new EIA system and found that the
      values measured by the previous system were 1.2-5.8-fold higher than the new
      system values. These results suggest that the previous system detected "hEGF" in
      excess owing to the nonspecificity of the antibody used. We investigated the
      molecular nature of immunoreactive hEGF detected in serum using our new system
      and confirmed that considerable amounts of immunoreactive hEGF exist as a high
      molecular weight form through S-S linkage with some macromolecule(s) in human
      blood as reported previously (Biochem Int 12:677-683, 1986).

PMID- 7714663
TI  - Colorimetrical rate assay for urinary dipeptidyl peptidase IV (DPPIV) activity
      using a new substrate.
AB  - We synthesized a new substrate glycyl-L-proline 3,5-dibromo-4-hydroxyanilide (Gly
      Pro-DBAP), for dipeptidyl peptidase IV (DPPIV). Its hydrolysis by DPPIV resulted
      in the formation of a chromophore, 2,6-dibromophenol-indo-p-xylenol, and its
      maximal absorption wavelength (600 nm) was longer than that of p-nitroaniline
      (415 nm) released from conventional substrate, glycyl-L-proline p-nitroanilide
      (Gly-Pro-pNA). We also established the rate assay for urinary DPPIV activity
      using Gly-Pro-DBAP. The optimum pH was between 8.5 and 9.0. The apparent Km was
      1.1 mmol/1. The detectable range was 2.5-350 U/l. No changes in blank values
      occurred throughout the enzyme reaction in the optimum pH. Its value was also
      much lower than Gly-Pro-pNA. CVs for within-run and between-run were 1.1% (n =
      10) and 3.0% (n = 10), respectively. Among tested peptidases, only DPPIV could
      hydrolyze Gly-Pro-DBAP. Among the protease inhibitors, only two, diprotin-A and
      phenylmethylsulfonyl fluoride (PMSA), could inhibit DPPIV activity. The present
      method did not interfere with urinary ingredients such as hemoglobin. The
      correlation between the present (y) and conventional (x) methods is presented by
      the equation y = 1.121x + 0.096 (r = 0.993). Thus the present method provides
      practical advantages over the conventional method for routine laboratory use.

PMID- 7714664
TI  - Detection of (1-3)-beta-D-glucan in a rat model of aspergillosis.
AB  - The G test containing factor G, fractioned from the Limulus lysate, was used to
      detect (1-3)-beta-D-glucan in a rat model of aspergillosis. Aspergillus fumigatus
      strain MF-13, 1 x 10(4) conidia, were inoculated transtracheally into rats
      treated with cortisone acetate (100 mg/kg) and fed a low-protein (8%) diet.
      Increased serum (1-3)-beta-D-glucan was found on the sixth day after inoculation
      in concentrations of 370 +/- 178 pg/ml (mean +/- SD) in untreated controls, and
      154 +/- 43 pg/ml in rats treated with 0.5 mg/kg of amphotericin B. On day 11 (1
      3)-beta-D-glucan concentrations were 2,590 +/- 2,940 pg/ml and 448 +/- 442 pg/ml,
      respectively. The elevation in levels of (1-3)-beta-D-glucan increased in
      correlation with the elevation of galactomannan antigen titers; (1-3)-beta-D
      glucan is thus measurable during experimental aspergillosis in rats.

PMID- 7714665
TI  - Review of in vivo pharmacokinetics and toxicology of phosphorothioate
      oligonucleotides.

PMID- 7714666
TI  - Acid citrate dextrose (ACD) formula A as a new anticoagulant in the measurement
      of in vitro platelet aggregation.
AB  - To evaluate whether the use of ACD Formula A may affect in vitro platelet
      function, blood samples were obtained from 21 healthy blood donors and
      anticoagulated in ACD (acid-citrate dextrose, NIH Formula A), Na citrate 3.8%,
      and K3EDTA. Platelet count, mean platelet volume, and in vitro platelet
      aggregation were evaluated on each sample. No significant difference was observed
      in platelet count and mean platelet volume among the different samples.
      Conversely, the ACD treated platelets showed a higher reactivity to the agonists
      as demonstrated by a significant increase of the maximum percentages of
      aggregation induced by ADP, epinephrine, and collagen, as well as a significant
      decrease of secondary aggregation thresholds to ADP and epinephrine. In
      conclusion, it may be speculated that ACD Formula A is capable of better
      maintaining the intraplatelet signal transduction mechanisms during PRP
      preparation, thus improving the overall responsiveness of platelets.

PMID- 7714667
TI  - Contribution of the host to test results in assays of Staphylococcus epidermidis.
AB  - From two human populations (one pediatric and one adult), clinically diagnosed
      with Staphylococcus epidermidis (S. epidermidis) sepsis of similar severity,
      bacteria were isolated from pre-antibiotic blood samples and evaluated for
      virulence. The LD50 of the bacteria in a mouse model was performed, with
      evaluation of animals dying acutely following intravenous S. epidermidis
      administration. More simple assays of virulence were also performed, including
      bacterial adherence to a fibrin clot and carbohydrate specific lectin binding.
      The eight pediatric-host S. epidermidis isolates required a significantly larger
      dose to produce lethality in dosed animals (LD50) when compared to the 20 adult
      host S. epidermidis isolates. The fibrin clot assay, a test that has corroborated
      bacterial virulence in endocarditis models, did not differentiate the groups: all
      but one of the 28 isolates were well above the adherence seen with the ATCC
      control, suggesting endocarditis-producing potential. Glycocalyx (slime) from
      eight of the more virulent isolates showed reactivity with a glucose-specific
      biotinylated lectin which was lacking in other isolates. Necropsy of mice dying
      at 12 hr showed S. epidermidis strain differences in specific organ effects.
      Overall, this study demonstrates the utility of the LD50 to provide a highly
      sensitive quantification of bacterial virulence. Necropsy of test animals dying
      acutely has showed an apparent organ tropism of some of these isolates which are
      usually considered harmless commensals.

PMID- 7714668
TI  - Quantification of mitogen induced human lymphocyte proliferation: comparison of
      alamarBlue assay to 3H-thymidine incorporation assay.
AB  - Proliferation of human lymphocytes in response to various stimuli has
      traditionally been assessed by measuring uptake of radiolabeled nucleotides such
      as 3H-thymidine. We have evaluated a fluorometric assay, which uses the
      commercially available reagent, alamarBlue, as a potential substitute for the 3H
      thymidine assay in measuring proliferation of human lymphocytes. In this assay,
      alamarBlue is added to a population of cells where it is reduced by mitochondrial
      enzyme activity. The reduced form of the reagent is fluorescent and can be
      quantitatively detected. The safety and convenience of the alamarBlue assay make
      it very attractive for use in the clinical laboratory. In this study peripheral
      blood mononuclear cells (PBMC) from healthy donors were stimulated using the
      mitogen Concanavalin A, and proliferation was assessed using either the 3H
      thymidine or the alamarBlue assay. The alamarBlue assay reliably detects human
      PBMC and we found that the linear range of detection was 10(4) cells/well (96
      well plate) to 5 x 10(5) cells/well. Detection of human PBMC is highly
      reproducible and the alamarBlue assay may be suitable in a number of applications
      where detection or relative quantitation of human PBMC is required. The
      alamarBlue assay also detected mitogen induced proliferation of PBMC although
      with a significantly lower level of sensitivity than the standard 3H-thymidine
      assay.

PMID- 7714669
TI  - Improvement of an EIA system for basic fibroblast growth factor by use of
      biotinylated antibody prepared with NHS-LC-biotin.
AB  - We improved our previously devised enzyme immunoassay (FIA) system for basic
      fibroblast growth factor (bFGF) using biotinylated antibody prepared with
      sulfosuccinimidyl-6-(biotinamido)hexanoate (NHS-LC-Biotin, Pierce), a water
      soluble biotin analogue, with an extended spacer arm. The discriminatory
      detection limit of the improved EIA was found to be 5 pg/ml (0.5 pg/assay tube),
      sixfold more sensitive than that of the previous system. The reproducibility of
      within- and between-assay series was 5.10-8.61% and 5.99-8.69%, respectively; and
      recovery of exogenous bFGF from serum was approximately 102%. Employing the
      improved EIA system, we investigated by chromatofocusing chromatography the
      isoelectric points of two immunoreactive bFGFs (high-molecular-weight bFGF-like
      immunoreactive substance, designated as HMW-bFGF-LI and 16-kd bFGF-LI, having the
      same molecular weight as recombinant bFGF) detected in serum from a breast cancer
      patient. As a result, the pI value of HMW-bFGF-LI was estimated to be 7.13, and
      that of 16 kd bFGF-LI, 9.58.

PMID- 7714670
TI  - Psoralen-protein photochemistry--a forgotten field.
AB  - 8-Methoxypsoralen in combination with long wavelength ultraviolet light is
      employed for the treatment of several cutaneous disorders, such as psoriasis,
      vitiligo and mycosis fungoides. It is common to attribute the efficacy of the
      photochemotherapy to the formation of psoralen DNA photoadducts. Thus, the main
      research effort has been directed towards the elucidation of nucleic acid
      photochemistry and related subsequent events (mutagenicity, toxicity). However,
      psoralens have been shown to undergo photoaddition reactions with other cellular
      components. In this review the status of psoralen-DNA photobiology is briefly
      summarized. The main focus, however, is on a survey of psoralen photochemical
      modification of proteins and the ways by which these additional photobiological
      events can impact the antigenicity and potentially immunogenicity of treated
      cells. Some preliminary results show the extent of psoralen-amino acid
      photoadduct formation and their impact on enzymatic processing.

PMID- 7714671
TI  - Formation of thymine-lysine and cytosine-lysine adducts in DNA-lysine
      photoconjugate.
AB  - Lysine was covalently conjugated to calf thymus DNA by irradiation with UV light
      (wavelength, 253.7 nm). The results showed monofunctional covalent photobinding
      of lysine molecules with bases in DNA. Only the epsilon-amino group of lysine
      participated in the photoconjugation reaction. Thymine and cytosine were modified
      by 60% and 25% respectively. The kinetics of the DNA-lysine photoreaction showed
      that one lysine molecule was in the photobound state per 10, 6, 5 and 4
      nucleotide base pairs of DNA on irradiation for 20, 30 40 and 60 min
      respectively.

PMID- 7714672
TI  - Involvement of H1 and other chromatin proteins in the formation of DNA-protein
      cross-links induced by visible light in the presence of methylene blue.
AB  - The formation of DNA-protein cross-links (DPCs), induced by irradiation with
      visible light, was studied in methylene blue-treated (MB-treated) chromatin and
      H1-depleted chromatin. The effects of the MB concentration and radiation dose
      were studied using sodium dodecylsulphate-chloroform-isoamyl alcohol assay and
      sodium dodecylsulphate-polyacrylamide gel electrophoresis. Under identical
      experimental conditions, DPC formation was less in H1-depleted chromatin (70%)
      than in chromatin (92%). The non-histone proteins and core proteins of chromatin
      contributed towards DPC formation. Of the core proteins, H2A was more cross
      linked than H4, whereas the bands for H2B and H3 melted into one in chromatin and
      H1-depleted chromatin. In both cases, the gel pattern showed the appearance of
      two new protein bands with approximate molecular weights of 27 kDa and 29 kDa as
      a result of histone-histone cross-linking. Viscometric studies showed that the
      dissociation of the compact structure of chromatin in 2 M NaCl was more extensive
      in irradiated, MB-treated, H1-depleted chromatin than in irradiated, MB-treated
      chromatin, indicating a reduction in the amount of DPC formation in H1-depleted
      chromatin.

PMID- 7714673
TI  - Photolabile "caged" adrenergic receptor agonists and related model compounds.
AB  - The synthesis and photochemical characterization of caged derivatives of the
      adrenergic receptor agonists phenylephrine, epinephrine and isoproterenol are
      described. These compounds were prepared using 2-nitrobenzyl or substituted 2
      nitrobenzyl photolabile protecting groups, and were designed to allow agonist
      concentration jumps to be made during pharmacological/physiological experiments.
      The advantage of this approach over conventional methods for changing the
      concentrations of agonists near receptors in mechanistic studies is the exquisite
      spatial and temporal resolution afforded by the use of light. Flash photolysis
      experiments revealed that photorelease is more than two orders of magnitude
      faster when the 2-nitrobenzyl group is attached to the beta-amino group rather
      than one of the phenolic oxygens of the catecholamine. For the caged
      phenylephrine derivatives, for example, the rate constants of release from the N
      linked and O-linked derivatives are 1.8 x 10(4) s-1 and 1.1 x 10(2) s-1
      respectively. However, the quantum yields of photorelease from the N-linked and O
      linked derivatives are similar. In addition, several model compounds were
      prepared to allow examination of the effects of substituents on the aromatic ring
      and benzylic carbon (of the 2-nitrobenzyl moiety) on the rates and efficiencies
      of photorelease. These studies revealed that, although substituents had little
      effect on the rates of photorelease from the N-linked caged derivatives, electron
      donating groups on the 2-nitrobenzyl ring increased the quantum yield of release
      by approximately fourfold, from 0.10 to 0.40. A summary of the studies completed
      to evaluate the biological properties of the caged adrenergic receptor agonists
      is also presented.

PMID- 7714674
TI  - Photodynamically induced cytotoxicity of hypericin dye on human fibroblast cell
      line MRC5.
AB  - The possible application of hypericin (hyp) in the photodynamic therapy (PDT) of
      cancer was investigated using the human fibroblast cell line MRC5. In aerobic
      conditions, at pH 7.4, irradiation of MRC5 cells was carried out with different
      doses of visible light and different doses of hyp. A low concentration of hyp (5
      x 10(-9) M) was highly toxic to MRC5 cells, producing 15% survival for an
      irradiation period of 40 min. In the dark, no cytotoxicity was observed in the
      range 10(-9)-10(-7) M hyp. The mechanism of cell killing by hyp was also
      examined. Significant inhibition of MRC5 killing was observed on addition of 1,4
      diazabicyclo[2,2,2]octane (DABCO) or histidine, known quenchers of type II
      mechanisms. In addition, the photodynamic effect of hyp was enhanced by deuterium
      oxide. The addition of desferrioxamine, catalase or superoxide dismutase (SOD),
      known scavenging agents of the type I mechanism, had a significant inhibitory
      effect on the rate of photodynamic action of hyp. The experimental results
      suggest that hyp has considerable potential for use as a sensitizer in the PDT of
      cancer.

PMID- 7714675
TI  - Sequence specificity of DNA-psoralen photoproduct formation in supercoiled
      plasmid DNA (pUC19).
AB  - Supercoiled pUC19 DNA, photoreacted with psoralen derivatives (xanthotoxin (8
      methoxypsoralen, 8-MOP), 4,5',8-trimethylpsoralen (TMP) and angelicin),
      influences the enzymatic activity of restriction enzymes in a different manner,
      although all the enzymes employed contain, within their recognition sites,
      suitable nucleic acid bases for photoproduct formation. The activity of the
      enzymes is strongly influenced by the photomodification of thymine residues
      within their recognition sites. 5'-TpA sequences favour intercalation as an
      essential prerequisite of the photoreaction, while 5'ApT sequences do not. This,
      in turn, influences photoproduct formation and the inhibition of the action of
      the restriction enzymes KpnI, SspI, DraI and RsaI, but not EcoRI and BamHI. The
      inhibitory effect is independent of the number of cleavage sites and also of
      whether monoaddition products or crosslinks are formed. Psoralen intercalation
      alone does not affect the activity of the restriction enzymes used.

PMID- 7714676
TI  - Photoreaction of 5-methoxypsoralen with thymidine. Isolation and characterization
      of a pyrone-side monoadduct involving the pyrimidine methyl group.
AB  - The UVA-mediated photoreaction of 5-methoxypsoralen (5-MOP) with thymidine has
      been investigated in the dry state. Under these conditions, the main products are
      5-MOP pyrone-side monoadducts to thymidine. We report the isolation and
      characterization of an unusual 5-MOP-thymidine photoproduct. The assignment of
      the photoadduct was achieved on the basis of extensive spectroscopic measurements
      (UV, mass spectrometry (MS), 1H and 13C nuclear magnetic resonance (NMR), nuclear
      Overhauser effect (NOE) experiments). The formation of the photoadduct, which is
      rationalized in terms of a radical mechanism, appears to involve, in a covalent
      bond, the C-4 pyrone moiety of 5-MOP and the methyl group of thymidine.

PMID- 7714677
TI  - To stab or strangle: how best to kill a varix?

PMID- 7714678
TI  - Intestinal lipoprotein metabolism.

PMID- 7714679
TI  - Differentiation and polarity alter the binding of IGF-I to human intestinal
      epithelial (Caco-2) cells.
AB  - This study examined whether insulin-like growth factor-I (IGF-I) bound to
      specific functioning IGF receptors on the surface of Caco-2 cells and how this
      binding was affected by the differentiation and polarity of these cells. IGF-I,
      which increased cell proliferation in a dose-dependent manner, bound to a
      specific receptor on the surface of Caco-2 cells. Affinity cross-linking with
      labeled IGF-I followed by reducing sodium dodecylsulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) showed M(r)s at 135,000, 270,000 and 355,000 bands,
      which was inhibited by unlabeled IGF-I. A Scatchard analysis of radioligand
      receptor binding showed the presence of a single class of receptors with high
      affinity for IGF-I. This class of receptors was specific for IGF-I, the affinity
      of IGF-I to the receptor being four and 150 times greater than IGF-II and
      insulin, respectively. There was no difference in the affinity of IGF-I to type 1
      IGF receptors between less-differentiated [dissociation constant (Kd) = 3.81 nM]
      and well-differentiated cells (Kd = 3.78 nM); however, well-differentiated cells
      showed a 2.4-fold higher maximum number of binding sites (Bmax) than less
      differentiated cells (3.45 vs. 1.44 x 10(4) sites/cell), indicating an increase
      in the density of IGF-I receptors with differentiation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7714680
TI  - Restitution of swallowing in the fetal sheep restores intestinal growth after
      midgestation esophageal obstruction.
AB  - We have shown that, in the fetal sheep, abolition of fluid ingestion early in
      gestation results in a profound gastrointestinal tract (GIT)-specific growth
      retardation and that these effects can be reversed if fetal swallowing is
      restored, even for relatively short periods (15 days). The fetal esophagus was
      ligated at 60-65 days of gestation in 11 fetal sheep (term is 145-148 days). At
      136 days of gestation, body and tissue growth of six fetuses were compared to
      eight age-matched control fetuses. There were no effects on body growth, but the
      growth of the GIT was significantly retarded. The small intestine was the most
      severely affected region; villi were smaller in both proximal and distal regions,
      and villus density was increased and crypt density decreased. The growth
      retarding effects are progressive such that they become more pronounced as the
      period of absence of swallowed input to the GIT is increased. Thus the effects
      observed in our study (ingestion abolished for approximately 80 days) are much
      more marked than those in our earlier short-term studies (40-50 days). Five of
      the fetuses with esophageal ligations underwent further surgery at approximately
      120 days' gestation to correct the esophageal obstruction so as to allow the
      resumption of fluid ingestion. By 136 days, the values of most intestinal
      morphological parameters had begun to move toward control values.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7714681
TI  - Fortification of human milk: evaluation of a novel fortification scheme and of a
      new fortifier.
AB  - Human milk fed to very-low-birth-weight infants must be fortified with protein,
      minerals, and vitamins. We tested a new fortification regimen in which the amount
      of fortifier was adjusted on the basis of frequent determinations of serum urea
      nitrogen (SUN). A newly formulated fortifier based on bovine milk proteins was
      employed either in the new fashion (regimen ADJ) or in the conventional fixed
      proportion (regimen FIX). Using the fixed proportion, the study also compared the
      new fortifier with a fortifier based on human milk protein (regimen HMP). Twelve
      infants were studied with each of the three regimens; nearly all completed 3
      weeks of study. Protein intake was generally higher in ADJ than FIX; the
      difference was significant (p < 0.01) during week 2. Weight gain was somewhat
      (but not significantly) greater in regimen ADJ (32.3 g/d or 18.8 g/kg/d) than in
      regimen FIX (30.0 g/d or 18.3 g/kg/d). SUN was higher in ADJ than in FIX, and
      several other serum chemical values (calcium, phosphorus, potassium) tended to be
      higher, probably reflecting higher intakes of these nutrients with ADJ than with
      FIX. Plasma concentrations of several amino acids were higher in ADJ than FIX,
      but none, including threonine, were outside the physiological range. In comparing
      regimen FIX to regimen HMP, infants on FIX received similar intakes of protein
      and showed slightly but not significantly more rapid weight gain. Concentrations
      of SUN were lower with FIX, but other serum chemical values, including amino
      acids, were generally similar to HMP. We conclude that use of the new adjustable
      fortification regimen is feasible and safe and that it should be studied further.
      It produced the expected increases in nutrient intakes and growth. The new bovine
      milk-based fortifier appears to be equivalent to the human milk-based fortifier.

PMID- 7714682
TI  - Etiology and risk factors of severe and protracted diarrhea.
AB  - Severe and protracted diarrhea (SPD) is the most severe form of diarrhea in
      infancy and has also been defined as intractable diarrhea. Its etiology is poorly
      defined. We have retrospectively evaluated the etiology, the outcome, and the
      risk factors of 38 children, admitted with protracted diarrhea and need for total
      parenteral nutrition (TPN) from 1977 to 1993. Children with anatomic
      abnormalities and/or primary immunodeficiency were excluded. There was an inverse
      relationship between the number of patients and the age of diarrheal onset (mean
      age, 2.9 +/- 3.5 months). Etiology of SPD was an enteric infection in 18 cases
      (eight Salmonella, three Staphylococcus, five rotavirus, one adenovirus, one
      Cryptosporidium), multiple alimentary intolerance (eight cases), familial
      microvillous atrophy (two), autoimmune enteropathy (two), celiac disease,
      lymphangectasia, eosinophilic enteropathy, intestinal pseudoobstruction, and
      intestinal neurodysplasia (1 case each). Etiology was not detected in three
      cases. Overall, 12 children died, five are presently being treated, and 21 had
      full remission. Comparative evaluation of risk factors between children with SPD
      and a control population of children with diarrhea but without the need for TPN
      showed that low birth weight, no breast feeding, history of fatal diarrhea in a
      relative, and early onset of diarrhea had a significantly higher incidence in the
      former. Social background was similar in the two populations. We conclude that a
      specific etiology can be identified in the majority of cases of SPD. The
      etiologic spectrum of SPD is broad, but an enteric infection is the most common
      cause of SPD. The severity of this condition is related, at least in part, to
      established risk factors.

PMID- 7714683
TI  - Fecal excretion of leukotriene C4 during human disease due to Shigella
      dysenteriae.
AB  - Fecal excretion of leukotriene C4 was determined in 26 individuals with dysentery
      and in 19 healthy controls. Of the patients, five were infected with Shigella
      dysenteriae type 1, 15 were infected with Shigella flexneri, two were infected
      with Shigella boydii, and four were infected with Shigella sonnei. Three of the
      healthy controls were infected with non-dysenteriae Shigellae. All isolates of
      Shigella dysenteriae type 1 produced Shiga toxin; the other strains were not
      toxigenic. Patients with dysentery due to Shigella dysenteriae type 1 excreted
      higher concentrations of leukotriene C4 (median, 3,234 pg/0.05 g of feces) than
      either ill individuals infected with non-dysenteriae Shigellae (median, 202
      pg/0.05 g) or healthy carriers (median, 145 pg/0.05 g) and uninfected controls
      (median, 129 pg/0.05 g). We propose that Shiga toxin stimulates intestinal mast
      cells, which release leukotriene C4, contributing to the inflammatory response in
      Shigella dysenteriae type 1-associated dysentery.

PMID- 7714684
TI  - Repeatability of the sugar-absorption test, using lactulose and mannitol, for
      measuring intestinal permeability for sugars.
AB  - Differential sugar-absorption tests for measuring intestinal permeability for
      sugars have been studied in a variety of gastrointestinal diseases. Their use in
      general practice has been hampered by a lack of data on reference values and
      repeatability of the test and the laboratory assay. In this study, we determined
      the reference values of the sugar-absorption test, using lactulose and mannitol
      as probe molecules, for children and adults. The repeatability of the test is
      good; linear relationship: slope, 0.825 [95% confidence interval (CI), 0.571,
      1.152); intercept, 0.005 (95% CI, -0.004, 0.010). The repeatability of the
      laboratory assay for the sugar-absorption test is excellent; linear relationship:
      slope, 1.014 (95% CI, 0.870, 1.094); intercept, 0.002 (95% CI, -0.005, 0.010).
      The validation of the sugar-absorption test makes the test useful as a simple,
      noninvasive, reliable intestinal permeability test for sugars, which can be of
      use for clinical practice. Taking possible interfering factors into account, the
      sugar-absorption test can be used as a diagnostic test for enteropathy of
      different etiologies and evaluation of therapeutic interventions in both children
      and adults. Studies with the sugar-absorption test may clarify the role of
      intestinal permeability in the pathophysiology of a variety of gastrointestinal
      diseases.

PMID- 7714685
TI  - Prospective study of lactose absorption during cancer chemotherapy: feasibility
      of a yogurt-supplemented diet in lactose malabsorbers.
AB  - Chemotherapy is a recognized cause of morphological alterations to the proximal
      intestine. Lactose malabsorption, the functional consequence of a small
      intestinal enzymatic derangement, has been shown to play an important role in
      causing gastrointestinal symptoms in subjects receiving chemotherapy. To
      establish a rational basis for the exclusion of lactose from the diet and to
      reduce the risk of developing gastrointestinal symptoms, we conducted a study of
      lactose absorption in 20 children during cancer chemotherapy. Because lactose is
      an important nutritional sugar, the tolerance of lactose provided by yogurt was
      examined. Lactose absorption was investigated by a hydrogen breath test (BT)
      after oral ingestion of milk (250 ml) containing physiological doses of lactose
      (12 g). The effect of yogurt supplementation was also tested by BT after meals of
      yogurt (450 g) also containing physiological doses of lactose (12.1 g). In 11
      children, lactose malabsorption was detected by BT during the study before any
      gastrointestinal symptom revealed this status. Of these 11 children, no
      gastrointestinal discomfort developed in five receiving a lactose-excluded diet.
      In contrast, in the six children not restricted in lactose intake,
      gastrointestinal symptoms were observed 4 to 13 weeks after lactose malabsorption
      was detected by BT. The findings of our study suggested the usefulness of dietary
      supplementation with yogurt, a lactose-containing food, in children who developed
      lactose malabsorption. In fact, all lactose-malabsorbent children showed good
      lactose absorption and tolerance when tested by yogurt BT.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7714686
TI  - The prognostic significance of caffeine half-life in saliva in children with
      chronic liver disease.
AB  - To evaluate its clinical value, the half-life of caffeine (1,3,7
      trimethylxanthine) in saliva (SCT) after 3 mg/kg-1 oral caffeine was measured in
      53 children with chronic liver disease (mean age, 4.41 years) and 48 control
      children (mean age, 6.26 years) in five samples over 24 h and compared with
      parameters of liver function and outcome. Sensitivity was 60.3% and specificity
      97% of SCT for diagnosis of chronic liver disease. The correlation of SCT with
      serum albumin (ALB) was -0.52 (p < 0.001), total bilirubin (SBR) was 0.585 (p <
      0.001), prolonged prothrombin time (PT) was 0.387 (p = 0.004), and aspartate
      aminotransferase (AST) was 0.538 (p = 0.001). The correlation of SCT with a
      clinical score of liver dysfunction calculated from the presence of features of
      hepatic decompensation was 0.627 (p < 0.001) and with Malatack's paediatric
      prognostic score was 0.505 (p < 0.001). Serial SCT and liver function tests were
      performed on 53 patients on 127 occasions during a mean follow-up of 361 days
      (range, 4-709). Of this group, 18 were listed for liver transplantation.
      Predictive values of outcome by analysis of variance expressed as ratio of mean
      squares were SBR, 34.1 (p < 0.001); log10 SCT, 20.6 (p < 0.001); ALB, 5.2 (p <
      0.05); PT, 1.2 (NS). SCT correlated with clinical and biochemical parameters of
      severity of liver disease, but SBR was a better predictor of listing for liver
      transplantation in this group of paediatric patients.

PMID- 7714687
TI  - Endoscopic ligation of esophageal varices in children.
AB  - Seven consecutive patients presenting acutely with suspected variceal hemorrhage
      underwent endoscopic variceal ligation (EVL) of esophageal varices. Active
      bleeding had ceased by the time of the initial EVL session in all patients,
      although active variceal hemorrhage was controlled by EVL in one patient during a
      subsequent episode of bleeding. Treatment sessions were repeated at approximately
      monthly intervals until varices were reduced in size to grade 1 (< 4 mm diameter)
      or eradicated. All patients had portal hypertension secondary to intrahepatic
      disease. Patient age ranged from 2.4 to 14.5 years (mean, 8.5 years). One patient
      underwent successful liver transplantation 1 week after the initial treatment
      session. The remaining six patients required a mean (+/- SD) of 4.0 +/- 1.3
      treatment sessions for elimination of varices. One episode of recurrent variceal
      hemorrhage and one episode of treatment-related hemorrhage occurred in two
      separate patients. Transient, mild dysphagia or odynophagia occurred in all
      patients. No other complications were reported during a mean (+/- SD) follow-up
      period of 13.8 +/- 4.6 months (range, 8-20 months). Recurrent varices were seen
      in three of four (75%) patients returning for follow-up endoscopy between 5 and 8
      months from initial eradication. All underwent repeat EVL without complication.
      Endoscopic variceal ligation may be a suitable substitute for sclerotherapy in
      children with bleeding esophageal varices.

PMID- 7714688
TI  - Characterization of symptoms in children with recurrent abdominal pain:
      resemblance to irritable bowel syndrome.
AB  - We sought to prospectively characterize and compare the symptoms of children > or
      = 5 years of age with recurrent abdominal pain to previously established criteria
      for irritable bowel syndrome (IBS) in adults. For all eligible subjects, a
      detailed questionnaire concerning characteristics of abdominal pain and
      defecatory pattern was completed at presentation. In addition, a battery of
      screening tests was performed and additional evaluation was done at the
      discretion of their physician. In all, 227 subjects fulfilled the entrance
      criteria, but 56 were subsequently excluded because of diagnoses of inflammatory
      bowel disease (nine cases), lactose malabsorption (46 cases), or celiac disease
      (one case). Of the remaining 171 patients, 117 had IBS symptoms. In the IBS
      subjects, lower abdominal discomfort (p < 0.001), cramping pain (p < 0.0009), and
      increased flatus (p < 0.0003) were more common, whereas dyspeptic symptoms such
      as epigastric discomfort (p < 0.003), pain radiating to the chest (p < 0.009),
      and regurgitation (p < 0.02) were more common in the non-IBS subjects. Our study
      not only confirms the clinical heterogeneity of children with recurrent abdominal
      pain but also concomitantly demonstrates that most children with this disorder
      have symptoms that fulfill the standardized criteria for IBS in adults. The
      identification of subgroups of children with recurrent abdominal pain can provide
      a framework for the diagnosis of functional bowel disease as well as establish
      the need for invasive and expensive tests.

PMID- 7714689
TI  - Sex differences in iron stores of adolescents: what is normal?
AB  - We evaluated iron status and its determinants in healthy adolescents. Fasting
      morning blood samples from a school-based cross-sectional study were analyzed for
      serum ferritin (SF), serum iron, total iron-binding capacity, and circulating
      transferrin receptors. Physical development, chronic disease, medication, dietary
      intake, and physical activity were assessed using clinical examination,
      questionnaires, and 7-day records. The risk of having low serum ferritin values
      was estimated using bivariate and multivariate regression. Subjects were 867
      healthy Swedish adolescents, 14- and 17-year-olds (472 boys and 395 girls). SF
      values increased with pubertal stage in boys but not in girls. Five percent of
      the boys and 15% of the girls had SF values < 12 micrograms/L. Of the 17-year-old
      boys, 7% compared to 1% of the 17-year-old girls had SF values > 100
      micrograms/L. Forty-one percent of cases with SF values > 12 micrograms/L had
      serum iron values < 15 microM, and 22% had transferrin saturation values < 16%.
      Mean total iron intakes of the boys were high [1.6 times recommended daily
      allowance (RDA)] and mean intakes of the girls were adequate (0.9 times RDA). Low
      heme iron intakes increased the risk of low iron stores (< 12 micrograms/L) in
      girls but not in boys. Total iron intake or other dietary factors, physical
      development, or level of physical activity did not influence the risk of low SF.
      The findings of this study suggest that the differences in iron status between
      boys and girls in adolescence results primarily from biological differences other
      than menstrual bleeding or insufficient iron intake. Furthermore, the results
      question the role of SF as an indicator of iron deficiency in adolescence, in
      particular if age and sex are not taken into consideration. We suggest that
      different reference values for SF, including the cut-off limit for low SF,
      adjusted for age and sex, should be considered. The high iron intakes and
      corresponding high SF values found in the older boys are noticeable in light of
      the possible negative health consequences of iron overload.

PMID- 7714690
TI  - Management of hepatic adenoma in glycogen storage disease Ia.

PMID- 7714692
TI  - Expression cloning of the ileal sodium-dependent bile acid transporter.

PMID- 7714693
TI  - Cell-to-cell spread of Shigella flexneri: exploitation of the host cytoskeleton.

PMID- 7714691
TI  - Chronic pancreatitis and obstructive jaundice from a round-cell tumor involving
      the pancreas.

PMID- 7714695
TI  - Hereditary hemorrhagic telangiectasia.

PMID- 7714696
TI  - Intestinal pseudoobstruction and phytobezoar.

PMID- 7714694
TI  - Fats charged with yet another count.

PMID- 7714697
TI  - Quantitative analysis of synaptic vesicle proteins in the aganglionic colon in
      rats with congenital aganglionosis.

PMID- 7714698
TI  - Glaucoma following childhood cataract surgery.
AB  - Glaucoma has been recognized as an infrequent but serious complication following
      surgery for congenital and acquired cataracts in childhood. Little is known
      concerning the influence of factors on the risk of glaucoma such as age at
      surgery, type of cataract, associated ocular abnormalities, and type of surgery.
      We reviewed records of 240 eyes of 155 patients on whom cataract surgery had been
      performed between January 1965 and July 1990 at Children's Hospital, Boston.
      After excluding those patients who had been followed up less than 5 years after
      surgery, and those who had had surgery after the age of 10 years, 125 eyes of 82
      patients were included in the study group. We identified 14 eyes of 9 patients
      that had developed open-angle glaucoma 5.3 to 13.1 years following surgery
      (average 7.4 years). An additional 4 eyes of 3 patients developed angle closure
      glaucoma, which was diagnosed at 146, 177, 2911, and 2939 days following surgery.
      A fifth patient developed acute angle closure 1.7 years following primary
      cataract surgery and 53 days following secondary discission. All but one of the
      patients who developed glaucoma had cataract surgery at less than 1 year of age.
      Age at surgery for the entire study group averaged 1.9 years, and ranged from 25
      days to 9.6 years. We conclude that patients having cataract surgery before 1
      year of age are at the greatest risk of developing postoperative open-angle
      glaucoma. Additional increased relative risk was found in eyes with microcornea,
      congenital rubella syndrome, and poor pupillary dilation with 1% cyclopentolate
      (Cyclogyl). No significant difference was seen among the various surgical methods
      of cataract removal.

PMID- 7714699
TI  - Congenital nasolacrimal duct obstruction: natural history and the timing of
      optimal intervention.
AB  - Nasolacrimal duct obstruction (NLDO) is a relatively common clinical problem.
      Debate continues about optimal management. Intervening early and intervening late
      each have advantages and disadvantages. We reviewed the world literature on NLDO.
      We assembled information on occurrence, natural history, and results of
      treatment. Spontaneous remission data were used to derive the probability of
      continued obstruction versus age. The prevalence a hypothesized treatment
      resistant form of NLDO was estimated. Symptomatic NLDO probably occurs in 5 to 6%
      of infants. Given a symptomatic case under the age of 14 months, the probability
      of spontaneous remission within the following month appears to be approximately
      one of three. Probe failure risk increases with age, doubling every 6 months.
      Increasing probe failure risk may be due to self-selection. Preliminary analysis
      of management strategies suggests that lacrimal duct probing at age 4 months in
      the office is the most cost-effective strategy. Further descriptive studies of
      NLDO remission and treatment are indicated.

PMID- 7714700
TI  - Dichoptic luminance beat visual evoked potentials in the assessment of
      binocularity in children.
AB  - Direct evidence of a distinct cortical binocular pathway has been provided by the
      production of nonlinear (difference) beats from dichoptic luminance stimulation
      in stereonormal adults and the absence or diminution of these beats in
      stereoblind subjects. We have investigated a clinically useful application of
      this technique in a pediatric population with potentially abnormal binocular
      vision. We recorded dichoptic luminance beat visual evoked potentials (VEPs) from
      20 children (ages 7 months to 8 years) with abnormal binocular ability secondary
      to strabismus and/or amblyopia and compared this to a control group of 20
      children with normal binocularity. Stereoblind children generated significantly
      lower dichoptic signal-to-noise ratios than stereonormal children (P < .001).
      Responses to monoptic multifrequency flicker were not significantly different
      between the two groups (P = .936). This dichoptic VEP can be performed quickly
      and easily on young children and gives a quantitative assessment of cortical
      binocularity that may not be determinable by standard clinical methods. This
      technique may also prove useful for the preoperative gradation of binocular
      potential and prediction of postoperative binocular fusion.

PMID- 7714701
TI  - Magnetic resonance imaging of the superior oblique muscle in superior oblique
      myokymia.
AB  - High resolution, magnetic resonance imaging was used to quantitatively study the
      morphometry of the superior oblique muscles of two patients with superior oblique
      myokymia, as well as 18 superior oblique muscles of 14 patients with normal
      superior oblique function. The cross sectional area of each superior oblique
      muscle was measured at 3-millimeter intervals along the entire muscle length. In
      both cases of myokymia, the affected superior oblique muscles were significantly
      smaller than normal (P < .05). These anatomical changes in the superior oblique
      muscle of patients with myokymia suggest that an antecedent injury to the
      trochlear nerve has occurred. This injury, even if clinically unapparent, may be
      the initial event which leads to subsequent development of superior oblique
      myokymia.

PMID- 7714702
TI  - Persistent tunica vasculosa lentis as a sign of congenital myotonic dystrophy.
AB  - We describe the ocular findings in eight patients with congenital myotonic
      dystrophy in the newborn period. While three infants had normal findings, five
      infants had evidence of persistent tunica vasculosa lentis (TVL) at gestational
      ages ranging from 34 to 40 weeks. Atrophy of vessels on the anterior lens capsule
      is normally complete by 34 weeks gestation and its persistence should suggest
      congenital infection or congenital myotonic dystrophy. Diagnosis of myotonic
      dystrophy has serious implications for the baby and the mother, in whom the
      condition may have not been recognized earlier.

PMID- 7714703
TI  - Idiopathic tractional corectopia.
AB  - Four infants were referred for congenital unilateral corectopia. In each case,
      the abnormal position of the pupil was caused by a fibrous structure that
      tethered the iris pupillary margin to the peripheral cornea. No patients showed
      characteristics of intrauterine infection, Rieger anomaly, ectopia lentis et
      pupillae, or iris coloboma. Amblyopia was not present in any of the patients.
      Three children demonstrated progression of the corectopia in the first 6 months
      of life. Two who developed shallow anterior chambers were treated surgically, one
      with an Nd:YAG laser and the other with incisional surgery. The third was treated
      with medical mydriasis. All four children have had favorable visual outcomes to
      date. The origin of the tethering strands is unclear but may be related to
      incomplete regression of vessels from the embryologic vascular system. We
      recommend medical or surgical intervention for unilateral corectopia when the
      pupillary aperture is displaced peripheral to the central visual axis or when the
      position of the iris threatens angle structures. Prophylactic occlusion therapy
      may also be indicated.

PMID- 7714704
TI  - Acquired central fusion disruption following cataract extraction.
AB  - Central sensory and motor fusion of images, once established, is usually
      maintained throughout life. Under certain circumstances, this ability may be
      lost. This gives rise to the syndrome known as horror fusionis, or acquired
      disruption of central fusion. We report the development of central fusion
      disruption in three patients with uniocular mature senile cataract. We postulate
      that this is the result of prolonged sensory deprivation in the cataractous eye.
      The loss of fusion results in a particularly troublesome type of intractable
      diplopia, characterized by the inability to either fuse or suppress images. To
      the best of the authors' knowledge, this is the first report of central fusion
      disruption following cataract surgery for senile cataract.

PMID- 7714705
TI  - Choroidal and orbital leukemic infiltrate mimicking advanced retinoblastoma.

PMID- 7714706
TI  - Ocular anomalies in the oral-facial-digital syndrome.

PMID- 7714707
TI  - Extragnathic cementoma.

PMID- 7714708
TI  - Treatment for congenital esotropia.

PMID- 7714709
TI  - Treatment of chronic sixth nerve palsy.

PMID- 7714710
TI  - Iron-binding affinity of bacterial vaccine polysaccharides which contain
      phosphodiester linkages as part of the polymer chain and of other polyphosphates,
      including DNA.
AB  - The interaction of iron (II) with bacterial polysaccharides, possessing
      phosphodiester bonds as part of their polymer chain, has been studied by
      equilibrium binding dialysis using atomic absorption spectrophotometry. Ferrous
      ions were found to bind with a stoichiometry of one per two phosphates and with a
      binding constant of about 2.5 x 10(3) M-1. Similar results, but with larger (ca 1
      x 10(4) M-1) binding constants were observed with DNA. This interaction helps
      explain the depolymerization of polyphosphates which has been observed in the
      presence of iron salts, and highlights the need to avoid iron contamination of
      vaccines (and other substances) which contain phosphodiester bonds. The
      interaction may also be a means of iron sequestration in bacteria which possess
      these cell-surface polyphosphates.

PMID- 7714711
TI  - Distribution and elimination of sulphadimethoxine and its metabolites in treated
      chicken.
AB  - Sulphadimethoxine (SDM), and its metabolites, N4-acetyl SDM, N1-(2-methyl-6
      hydroxy-4-pyrimidinyl) sulphanilamide (6-OH-SDM), N1-(6-methyl-2-hydroxy-4
      pyrimidinyl) sulphanilamide (2-OH-SDM), N1-(2,6-dihydroxy-4-pyrimidinyl)
      sulphanilamide (2,6-diOH-SDM) and SDM N1-glucuronide in chicken tissues were
      extracted, partially purified by Bond Elute SCX cartridges, and assayed and
      identified by HPLC/LC-MS after administration of SDM to chickens. During the
      administration and 24 h after withdrawal, SDM and 6-OH-SDM were observed in
      almost all tissues and excreta. N4-Acetyl SDM and 2,6-diOH-SDM were observed in
      some tissues, but 2-OH-SDM and SDM N1-glucuronide were observed in a few limited
      tissues. Twenty four hours after withdrawal, SDM and its metabolites, except 6-OH
      SDM, decreased. SDM and its metabolites were eliminated from all tissues within
      48 h of withdrawal.

PMID- 7714712
TI  - Curcuminoids as potent inhibitors of lipid peroxidation.
AB  - Earlier studies showed that curcumin is a potent inhibitor iron-catalysed lipid
      peroxidation. Demethoxycurcumin, bisdemethoxycurcumin and acetylcurcumin were
      tested for their ability to inhibit iron-stimulated lipid peroxidation in rat
      brain homogenate and rat liver microsomes. Comparison of the results with
      curcumin showed that all compounds are equally active, and more potent than alpha
      tocopherol. These results showed that the methoxy and phenolic groups contribute
      little to the activity. Spectral studies showed that all compounds could interact
      with iron. Thus, the inhibition of iron-catalysed lipid peroxidation by
      curcuminoids may involve chelation of iron.

PMID- 7714713
TI  - Fenbufen pretreatment potentiates the anticonvulsant activity of CPPene and NBQX
      in DBA/2 mice.
AB  - The anticonvulsant activity of 3-((+/-)-2-carboxypiperazin-4-yl)-1-propenyl-1
      phosphonic acid (CPPene) and 2,3-dihydroxy-6-nitro-7-sulphamoyl
      benzo(F)quinoxoline (NBQX), two excitatory amino acid antagonists, was studied
      against audiogenic seizures in DBA/2 mice, following intraperitoneal (i.p.) or
      intracerebroventricular (i.c.v.) administration. Maximal anticonvulsant
      protection was observed 15-30 min following NBQX and 45-180 min after CPPene.
      Coadministration with fenbufen (20 mg kg-1, i.p.), a non-steroidal anti
      inflammatory agent, enhanced and prolonged the anticonvulsant actions of CPPene
      and NBQX and also potentiated and prolonged the impairment of rotarod
      performance. The enhancement of the anticonvulsant activity and the prolonged
      impairment of rotarod performance suggests that fenbufen may have some
      pharmacokinetic interactions with CPPene and NBQX and that fenbufen is able to
      increase the brain levels of these excitatory amino acid antagonists. In
      particular, fenbufen was able to exert a major degree of potentiation of effects
      of NBQX rather than those of CPPene, suggesting that the chemical structures of
      these excitatory amino acid antagonists are responsible for the different degree
      of interactions between CPPene or NBQX and fenbufen. NBQX appears to have a
      notable similarity with quinolones whilst CPPene does not. Additionally fenbufen
      may displace CPPene and NBQX from plasma binding sites or inhibit the renal
      excretion. The present data are also consistent with previous studies showing
      pharmacokinetic interactions between fenbufen and quinolones.

PMID- 7714714
TI  - Continuous administration of low dose rates of physostigmine and hyoscine to
      guinea-pigs prevents the toxicity and reduces the incapacitation produced by
      soman poisoning.
AB  - A regime was developed, using mini-osmotic pumps, for the continuous subcutaneous
      administration of low doses of physostigmine (12.1, 9.7, 4.85 and 2.43 micrograms
      h-1), in combination with hyoscine (1.94 or 0.39 micrograms h-1), to guinea-pigs
      for up to 13 days. Physostigmine, in combination with hyoscine, inhibited plasma
      cholinesterase, and red blood cell and brain acetylcholinesterase, in a
      concentration-dependent manner, did not affect the normal growth rate of guinea
      pigs, and produced no obvious signs of poisoning. A dose rate of 4.85 micrograms
      h-1 physostigmine and 1.94 micrograms h-1 hyoscine was required to inhibit red
      cell acetylcholinesterase by 30% and brain acetylcholinesterase by 5-15%, with an
      accompanying plasma hyoscine concentration of 700-850 pg mL-1. There was an
      apparent decline in red cell acetylcholinesterase activity during the 13 days.
      Hyoscine levels were higher in the cholinergic-rich areas of the brain than in
      the plasma. Continuous pretreatment (1 or 6 days) with physostigmine (4.84
      micrograms h-1) and hyoscine (1.94 micrograms h-1) provided complete protection
      against the lethal effects, and minimized the incapacitation and weight loss
      produced by soman at a dose equivalent to the LD99 value. Following soman
      challenge, guinea-pigs exhibited early signs of soman poisoning, but generally
      these signs of poisoning were minimal by 1-2 h. Extending the pretreatment time
      to 13 days protected 75% of the guinea-pigs against the lethal effects of soman
      poisoning. Red cell acetylcholinesterase activity, 24 h after soman poisoning,
      was higher following continuous pretreatment with physostigmine and hyoscine than
      after acute treatment with atropine.

PMID- 7714715
TI  - The effect of three H2-receptor antagonists on the disposition of midazolam in
      the rat in-situ perfused liver model.
AB  - The rat in-situ perfused liver model was used to investigate the effect of three
      H2-receptor antagonists on the pharmacokinetic disposition of the short-acting
      benzodiazepine, midazolam. Perfusion experiments, using standard techniques, were
      carried out on four groups (one control and three H2-receptor antagonist-treated
      groups) of male Sprague-Dawley rats (300-350 g). All animals received midazolam 1
      mg; the three treated groups received cimetidine (8 mg), ranitidine (3 mg) or
      famotidine (0.4 mg). Perfusate and bile samples were collected and assayed for
      midazolam using gas chromatography. The perfusate data indicated that midazolam
      disposition was impaired at 10, 50 and 60 min of the experimental period
      following the addition of cimetidine, whereas ranitidine and famotidine produced
      an effect at 10 min only; midazolam levels in bile were not affected by the
      presence of an H2-receptor antagonist. It was concluded that the limited
      inhibitory effect of cimetidine may be attributed to its lack of specificity for
      CYP3A, the isoenzyme responsible for the metabolism of midazolam.

PMID- 7714716
TI  - Upregulation of antithrombotic ectonucleotidases by aspirin in human endothelial
      cells in-vitro.
AB  - Ecto ATP-diphosphohydrolase (apyrase) activity of human endothelial cells
      following aspirin treatment has been studied in-vitro. It was shown by HPLC
      analysis of supernatant samples that pre-incubation of the cultures with aspirin
      resulted in a significantly increased turnover of supplemented ATP into its
      degradation products (ADP and AMP). Enhanced expression of ectoenzyme after
      aspirin treatment could be observed as demonstrated by immunofluorescence
      staining with monoclonal anti-apyrase antibodies. This suggests enhancement of
      endothelial ATP-diphosphohydrolase activity induced by aspirin. The present data
      obtained in human vascular cells in-vitro are in line with results from previous
      animal studies in-vivo, suggesting a novel cyclooxygenase-independent
      antithrombotic activity of aspirin.

PMID- 7714717
TI  - What is the point of pharmacokinetics?

PMID- 7714718
TI  - Chemical incompatibility between procainamide hydrochloride and glucose following
      intravenous admixture.
AB  - The chemical reaction between procainamide hydrochloride and glucose following
      admixture to glucose infusion has been investigated. Substantial amounts (10-15%
      after 10 h at room temperature) of the procainamide is lost with the formation of
      a mixture of the corresponding alpha- and beta-glucosylamines. The chemical
      identity of the latter compounds was confirmed by 13C and 1H nuclear magnetic
      resonance spectroscopy.

PMID- 7714719
TI  - Deep tissue penetration of bases and steroids after dermal application in rat.
AB  - The local deep tissue penetration of bases such as diazepam, antipyrine,
      iodoantipyrine, haloperidol and steroids such as hydrocortisone, fluocinolone
      acetonide, testosterone and progesterone after dermal application as aqueous
      solutions was studied in a rat model. The extent of local, as distinct from
      systemic delivery, for each solute was assessed by comparing the tissue
      concentrations obtained below a treated site with those in contralateral tissues.
      Local direct penetration was evident for all solutes below the applied site,
      although depth of penetration varied between individual solutes. A physiological
      pharmacokinetic model was employed to estimate local tissue concentrations of
      various compounds after dermal application.

PMID- 7714720
TI  - The metabolism of a series of ester pro-drugs by NCTC 2544 cells, skin homogenate
      and LDE testskin.
AB  - The metabolism of a series of substituted pyrazolopyridine ester pro-drugs was
      investigated using NCTC 2544 cells, human skin homogenate and LDE Testskin as
      model systems. The compounds were incubated in each system and the disappearance
      of drug and the production of the major hydrolysis product was observed with time
      and quantitated using HPLC. The toxicity of the ester pro-drugs and the
      metabolites was examined in NCTC 2544 cells using a cell viability assay
      procedure. Hydrolytic activity was slightly higher in the cell culture model than
      in skin homogenate solution but the rank order of activity for each pro-drug was
      similar. The metabolic activity of LDE Testskin was much reduced compared with
      the other systems, but again the overall pattern of metabolism was not
      dissimilar. These findings indicate that NCTC 2544 cells provide a reasonable
      model for human skin ester hydrolysis both in terms of rate and in terms of
      substrate specificity.

PMID- 7714722
TI  - Kojic acid, a cosmetic skin whitening agent, is a slow-binding inhibitor of
      catecholase activity of tyrosinase.
AB  - It was found that kojic acid, which is used in cosmetics for its excellent
      whitening effect, inhibits catecholase activity of tyrosinase in a non-classical
      manner. A decrease in the initial velocity to a steady-state inhibited velocity
      can be observed over a few minutes. This time-dependence, which is unaltered by
      prior incubation of the enzyme with the inhibitor, is consistent with a first
      order transition. The kinetic data obtained correspond to those for a postulated
      mechanism that involves the rapid formation of an enzyme inhibitor complex that
      subsequently undergoes a relatively slow reversible reaction. Kinetic parameters
      characterizing this type of inhibition were evaluated by means of nonlinear
      regression of product accumulation curves.

PMID- 7714721
TI  - Liposomes as in-vivo carriers for citicoline: effects on rat cerebral post
      ischaemic reperfusion.
AB  - Citicoline is a therapeutic agent widely used in the treatment of brain injury,
      for example in cerebrovascular disease or traumatic accidents. Unfortunately, the
      strong polar nature of this drug prevents it crossing the blood-brain barrier. In
      this paper, the possibility of efficiently trapping citicoline in liposomes to
      improve its therapeutic effects is reported. The citicoline-encapsulation
      efficiency, drug leakage and size analysis of various liposome systems were
      studied. The real therapeutic effectiveness of these citicoline liposome
      formulations was evaluated by biological assay. The effects of free and liposome
      encapsulated citicoline on survival rate of ischaemic reperfused male Wistar rats
      (80-100 g) were investigated. Of the phospholipid mixtures used in citicoline
      liposome formulation the best in terms of delivery and therapeutic effects was
      1,2-dipalmitoyl-sn-glycero-phosphocholine: dipalmitoyl-DL-alpha-phosphatidyl-L
      serine:cholesterol (7:4:7 molar ratio). This phospholipid mixture was also
      assayed for brain conjugated diene levels in rats, since this parameter is an
      index of lipid peroxidation in rat cerebral cortex during post-ischaemic
      reperfusion. A citicoline-loaded phospholipid mixture has produced an increase in
      rat survival rate of about 24% and a reduction in diene levels of 60%, compared
      to the free drug.

PMID- 7714723
TI  - Physicochemical characterization and acute toxicity evaluation of a positively
      charged submicron emulsion vehicle.
AB  - Fine, homogeneous, positively-charged emulsions with a mean droplet size of 138
      +/- 71 nm and a zeta potential value of 41.06 mV were prepared using a
      combination of emulsifiers comprising phospholipids, poloxamer 188, and
      stearylamine. The pH of these emulsions decreased with time. However, the extent
      of decrease was dependent on the storage temperature. The mean droplet size of
      the emulsions that had been prepared with 1% poloxamer began to increase slightly
      after six months' storage, particularly when stored at 23 and 37 degrees C.
      However, emulsions prepared with 2% poloxamer remained stable for at least 10
      months at 4 degrees C, suggesting that the poloxamer 188 concentration is
      critical for prolonged emulsion stability. The results of the ocular tolerance
      study in rabbit eye indicate that hourly administration of a positively-charged
      emulsion vehicle was well tolerated without any toxic or inflammatory response to
      the ocular surface during the five days of the study. Scanning electron
      microscopy revealed a normal corneal surface, which was not different from that
      of the animals treated with physiological saline. No marked acute toxicity was
      observed when 0.6 mL of positively-charged emulsion was injected intravenously to
      BALB/c mice. Furthermore, no difference was noted between this group of animals
      and the group injected with the marketed Intralipid emulsion. These results were
      further confirmed in a rat study where there were no deaths following intravenous
      injection of 3.3 mL per rat of the positively-charged emulsion or Intralipid.
      Neither emulsion elicited any hepatotoxic or nephrotoxic effects. The overall
      results suggest that the novel positively-charged emulsion is suitable for
      parenteral use, and for ocular application.

PMID- 7714724
TI  - Lipophilicity of teicoplanin antibiotics as assessed by reversed phase high
      performance liquid chromatography: quantitative structure-property and structure
      activity relationships.
AB  - Structure-lipophilicity relationships of a large series of 63-COX teicoplanin
      antibiotic derivatives were examined, by correlating their capacity factors (log
      kw), measured through reversed-phase high-performance liquid chromatography on
      Deltabond C8 stationary phase, with some computed molecular properties such as
      fragmental log P constants (pi x), molecular volumes (Vx) and factors imparting
      hydrophilicity (e.g. amino groups in the X chain, nN). A number of equations were
      derived which demonstrate that variations of log kw are mainly related to changes
      in bulk (modelled by Vx) and polarity (primarily modelled by nN) of X chains of
      teicoplanin derivatives. QSAR analysis revealed that in-vitro activity against E.
      coli increases as lipophilicity decreases and isoelectric point increases.

PMID- 7714725
TI  - Provision and receipt of social support and disregard: what is their impact on
      the marital life quality of infertile and fertile couples?
AB  - A longitudinal study examined perceptions of received and provided social support
      and disregard among members of 248 infertile and fertile married couples.
      Correlational and structural equation modeling analyses were conducted. Women's
      and men's perceptions of the amount of social support they gave to and received
      from their partner were highly positively related. In contrast, agreement between
      spouses about the amount of provided support was moderate. Both social support
      and disregard mediated the relationships between stress and marital quality of
      life. Overall, highly similar patterns of results were found for members of
      infertile and fertile couples. These results demonstrate the perceptual element
      of received support and disregard as well as the importance of considering the
      provider's perspective.

PMID- 7714726
TI  - Changes in mood during acute hypoglycemia in healthy participants.
AB  - Acute hypoglycemia provides a reproducible method of investigating the effect of
      biological changes induced during hypoglycemia on mood states. Hypoglycemia was
      induced twice using a hyperinsulinemic glucose clamp in 24 nondiabetic human
      participants; a euglycemic placebo control study was also performed. Serial
      changes in mood were assessed using the UWIST Mood Adjective Checklist before,
      during, and after 60 min of controlled hypoglycemia (2.5 mmol/l). Hypoglycemia
      induced a significant reduction in hedonic tone (p = .001), a significant
      increase in tense arousal (p < .0005), and a significant decline in energetic
      arousal (p = .01) in comparison with the euglycemia control study. Profound
      changes in mood were observed in nondiabetic participants during acute
      hypoglycemia, and a state called tense tiredness persisted for at least 30 min
      after restoration of euglycemia.

PMID- 7714727
TI  - Relations of shyness and low sociability to regulation and emotionality.
AB  - The relations of shyness and low sociability (i.e., the nonfearful preference to
      be alone) to measures of regulation and emotionality were examined. College
      students and (for some variables) friends reported on their relevant
      dispositional characteristics. In general, shyness was associated with low
      regulation and high negative emotionality (including intensity, negative
      affectivity, and personal distress), low positive affect, and low constructive
      coping. In contrast, low sociability was unrelated to negative emotionality;
      associated with low positive emotional intensity, low physiological reactivity,
      and high inhibition control; and correlated with low seeking of social support as
      a means of coping. The findings are considered within a heuristic model in which
      emotional reactivity and regulation are proposed as predictors of social
      responding.

PMID- 7714728
TI  - Coherence and congruence: two aspects of personality integration.
AB  - Coherence and congruence-based measures of personality integration were related
      to a variety of healthy personality characteristics. Functional coherence was
      defined as occurring when participants' "personal strivings" (R.A. Emmons, 1986)
      help bring about each other or help bring about higher level goals. Organismic
      congruence was defined as occurring when participants strive for self-determined
      reasons or when strivings help bring about intrinsic rather than extrinsic higher
      level goals. Study 1 found the integration measures were related to each other
      and to inventory measures of health and well-being. Study 2 showed that these
      goal integration measures were also related to role system integration and were
      prospective predictors of daily mood, vitality, and engagement in meaningful as
      opposed to distracting activities.

PMID- 7714729
TI  - Synthesis and structural, conformational, biochemical, and pharmacological study
      of new compounds derived from tropane-3-spiro-4'(5')-imidazoline as potential 5
      HT3 receptor antagonists.
AB  - A series of tropane-3-spiro-4'(5')-imidazolines was synthesized and studied by 1H
      and 13C NMR spectroscopy, and the crystal structure of 2'-(1H-indol-3-yl)tropane
      3-spiro-4'(5')-imidazoline hydrochloride 5(6)f was determined by X-ray
      diffraction. In CD3OD solution, compounds 5(6)a-f display the same preferred
      conformation. The pyrrolidine and piperidine rings adopt an envelope conformation
      flattened at N8 and a distorted chair conformation puckered at N8 and flattened
      at C3, respectively, with the N-substituent in the equatorial position with
      respect to the piperidine ring. This conformation is similar to that observed for
      compound 5(6)f in the solid state. From binding studies on the compounds
      synthesized, compound 5(6)d demonstrated the ability to efficiently displace the
      binding of [3H]GR65630 to bovine brain area postrema membranes to an extent
      comparable to MDL 72222. In the von Bezold-Jarisch reflex, compound 5(6)d was
      equipotent with metoclopramide. It is, therefore, likely that the imidazoline
      ring may provide a useful bioisosteric replacement for the carbonyl group in 5
      HT3 antagonists.

PMID- 7714730
TI  - Scavenger effect of vitamin E and derivatives on free radicals generated by
      photoirradiated pheomelanin.
AB  - The free radical scavenger properties of vitamin E (DL-alpha-tocopherol), a
      natural antioxidant, and derivatives were studied using an original in vitro
      method consisting of free radical production by photoirradiation of pheomelanin
      and direct detection of the free radicals by a physical, specific technique,
      electron spin resonance. Validation of this method has been realized using well
      known biological free radical scavengers, superoxide dismutase and reduced
      glutathione. DL-alpha-Tocopherol, tocopheryl acetate, tocopheryl linoleate, and
      tocopheryl polyoxyethylene (POE) succinate induced a significant diminution of
      the free radical production. In order of efficiency, tocopheryl POE succinate was
      the best scavenger (37.6% inhibition at 0.25%) followed by tocopheryl linoleate
      (25.6% inhibition at 1%) and tocopheryl acetate (23.9% inhibition at 0.5%) and
      finally DL-alpha-tocopherol (16.2% inhibition at 0.05%). The results reported a
      decrease of the inhibitory effect for high concentrations of DL-alpha-tocopherol
      (0.1%) and tocopheryl acetate (1%), showing a tendency of this compound to act as
      a prooxidant. Used in optimal concentrations in cosmetologic or dermatologic
      formulations, Vitamin E and these derivatives should prevent or reduce the
      harmful activity of free radicals in the skin.

PMID- 7714731
TI  - Pharmacokinetics of promazine in patients with hepatic cirrhosis--correlation
      with a novel galactose single point method.
AB  - We examined promazine pharmacokinetics in nine patients with hepatic cirrhosis
      and in six healthy subjects. A specific and sensitive HPLC method was used to
      measure promazine concentrations in plasma, plasma water (free drug), red blood
      cells, and urine after oral administration of promazine (2 x 50 mg tablet). There
      were highly significant reductions in total plasma clearance (p < 0.01), free
      drug total plasma clearance (p < 0.01), metabolic clearance (p < 0.01), metabolic
      clearance of free drug (p < 0.01), and fraction bound (p < 0.01) in the cirrhotic
      patients. The elimination half-life and the area under the plasma concentration
      time curve were significantly increased (p < 0.001 and p < 0.05, respectively) in
      the cirrhotic patients. However, the overall excreted promazine in urine, time to
      the promazine peak concentration, distribution half-life, renal clearance,
      apparent volume of distribution, and the promazine concentration ratio between
      plasma and red blood cells were not different. Thus caution is needed in using
      promazine for patients with hepatic cirrhosis. A newly developed galactose single
      point (GSP) method was applied to quantitatively measure the residual liver
      function in cirrhosis patients and successfully correlated it with promazine
      elimination half-life (r = 0.770, p < 0.01), total plasma clearance of free drug
      (r = 0.899, p < 0.005), metabolic clearance of free drug (r = 0.902, p < 0.005),
      and plasma protein binding (r = 0.822, p < 0.005). GSP may be a convenient index
      for promazine routine dosage adjustment in patients with liver
      cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714732
TI  - Transesterification reactions of parabens (alkyl 4-hydroxybenzoates) with polyols
      in aqueous solution.
AB  - Accelerated stability tests of aqueous solutions containing parabens and polyols
      were performed using concentrations similar to pharmaceutical and cosmetic
      formulations. Reaction products were detected in these solutions by HPLC and
      identified by chromatographic and spectroscopic means. Using xylitol and
      methylparaben as model reactants, three unknown peaks having the relation 1:2:4
      were obtained together with the hydrolysis product 4-hydroxybenzoic acid. Diode
      array detection gave identical UV spectra for each peak with a maximum at 255 nm.
      The structures of the isomeric 1-, 2-, and 3-xylityl 4-hydroxybenzoic acid esters
      were proved by means of LC-MS, GC-MS, and NMR and correlated to the peaks in the
      HPLC chromatograms. The rate of the transesterification was shown to be highest
      in strongly alkaline medium (ph 10-11), whereas equilibration of the reaction was
      optimally balanced at pH 8-9. An increase of polyol concentration enhanced the
      formation of the esters. The reactivity of different substituted parabens was
      higher in the case of parabens with a short alkyl ester function. Similar
      reaction profiles were observed with C3-C6 polyols, but no transesterification
      took place when aldoses were used.

PMID- 7714733
TI  - Interaction between Cu2+ ions and cholic acid derivatives followed by
      polarography.
AB  - Interaction of bile salts with Cu2+ ions in unbuffered systems containing 0.15 M
      NaNO3 was followed by measuring polarographic limiting currents and half-wave
      potentials. Whereas taurocholate forms neither soluble complexes nor compounds of
      limited solubility, cholate, glycocholate, and dehydrocholate from both soluble
      complexes and slightly soluble salts of copper(II) with small aggregates of bile
      salts. The stability of soluble complexes is comparable for cholates,
      dehydrocholates, acetates, and acetylglycinates, but smaller for glycocholates.
      The solubility of the copper(II) salts with small aggregates decreases in the
      sequence: glycocholate > cholate >> dehydrocholate. It is proposed that these
      salts are formed by interaction of a copper(II) ion with two carboxylic groups
      located on the small aggregate in a sufficiently small distance. In the presence
      of excess cholate the precipitated copper(II) salts are dissolved. It is assumed
      that at high bile salt concentrations, where precipitates are not observed,
      larger aggregates are formed that have free carboxylate groups, which increase
      their solubility in aqueous solutions. For glycocholate, within the accessible
      concentration range and within the time-frame used (24 h for the establishment of
      the equilibrium), the formation of such larger aggregates was not observed, even
      when its "cmc" is comparable with that of cholate. The absence of formation of
      larger aggregates for dehydrocholate parallels its tendency not to form
      "micelles".

PMID- 7714734
TI  - Pharmacokinetics of tiqueside (beta-tigogenin cellobioside) in dogs, rats,
      rabbits, and monkeys.
AB  - Tiqueside (CP-88,818, beta-tigogenin cellobioside) is an effective cholesterol
      absorption inhibitor that may be useful in the treatment of hypercholesteremia.
      We have investigated the pharmacokinetics of tiqueside in dogs, rats, rabbits,
      and monkeys. In dogs, the volume of distribution (Vdss) was 2.11 L/kg, clearance
      was 0.58 mL/min-kg, and half-life was 45 h following a 1.4 mg/kg intravenous
      dose. Absolute bioavailability in fed dogs decreased from 6.7% for a 30 mg/kg
      dose to 1.7% for a 375 mg/kg dose. The oral bioavailability at a dose of 375
      mg/kg was approximately 4-fold lower in fasted dogs than fed dogs. AUC-(0-24) for
      doses up to 2000 mg/kg were only slightly greater than AUC-(0-24) for a 375 mg/kg
      dose. In rats dosed intravenously at 8.0 mg/kg, Vdss was 3.52 L/kg, clearance was
      14.6 mL/min-kg, and half-life was 3.6 h. Estimated bioavailability for rats dosed
      in feed at 250-2000 mg/kg/day was less than 0.5%. In rabbits dosed at 4.0 mg/kg
      i.v., Vdss was 2.95 L/kg, clearance was 0.59 mL/min-kg, and half-life was 61 h.
      Bioavailability for rabbits dosed in feed at 62.5 or 125 mg/kg/day was
      approximately 7%. Systemic exposure in rhesus monkeys after oral dosing was lower
      than that for dogs and rabbits. Thus, low systemic exposure to tiqueside
      following oral administration has been demonstrated in several animal species.

PMID- 7714735
TI  - Kinetics and mechanism of the alkaline hydrolysis of securinine.
AB  - The hydroxide ion-catalyzed hydrolysis of securinine involves the ring opening of
      the lactone moiety. The rate of hydrolysis is insensitive to the ionic strength.
      The observed pseudo-first-order rate constants reveal a decrease of approximately
      4-fold due to the increase in the MeCN content from 4 to 50% (v/v) in mixed
      aqueous solvent. The temperature dependence of the rate of hydrolysis follows the
      Eyring equation, which yields delta H* and delta S* as 11.0 kcal mol-1 and -34.5
      cal deg-1 mol-1, respectively. The hydroxyl carboxylate product of the alkaline
      hydrolysis of securinine is shown to undergo cyclization in acidic medium to
      yield securinine. The observed pseudo-first-order rate constants for cyclization
      increase linearly with an increase in [H+]. The change in the content of MeCN
      from 3.8 to 47.2% (v/v) in mixed aqueous solvents does not show an effect on the
      rate of the cyclization reaction. The most plausible mechanisms for alkaline
      hydrolysis and acid cyclization reactions are also discussed.

PMID- 7714737
TI  - High-affinity rabbit antibodies directed against methotrexate: production,
      purification, characterization, and pharmacokinetics in the rat.
AB  - We describe the production, purification, characterization, and disposition of
      rabbit polyclonal methotrexate antibodies. These antibodies are prepared for
      subsequent testing of a drug delivery approach to reduce systemic toxicity upon
      regional administration of methotrexate. The polyclonal antibodies were raised in
      New Zealand white female rabbits immunized with a methotrexate-bovine serum
      albumin conjugate. The anti-methotrexate antibodies were sequestered from rabbit
      serum through the use of a protein-G affinity column which allowed for
      purification of up to 100 mg of rabbit IgG in 30-40 min. The extent of
      purification was demonstrated through SDS-PAGE and calculation of specific
      binding activity relative to total protein concentration. The purified antibodies
      have been shown to have high affinity (Keq range: 1.8 x 10(8) to 8.75 x 10(9) M
      1) and high selectivity for methotrexate. Preliminary pharmacokinetic studies of
      the purified antibodies in the rat following a 6 mg/kg intravenous infusion (n =
      4) indicate a steady state volume of distribution of 38.0 +/- 11.2 mL kg-1, a
      systemic clearance of 0.92 +/- 0.67 mL kg-1 h-1 and an elimination half life of
      28.9 +/- 7.9 h (mean +/- SD).

PMID- 7714736
TI  - Modification of rectal absorption of morphine from hollow-type suppositories with
      a combination of alpha-cyclodextrin and viscosity-enhancing polysaccharide.
AB  - An attempt was made to optimize the rectal delivery of morphine, using
      cyclodextrins as an absorption enhancer and polysaccharides as a swelling
      hydrogel in Witepsol H-15 hollow-type suppositories, and this was tested in
      rabbits. alpha- and beta-cyclodextrins enhanced the rate and extent of
      bioavailability, the former being more effective; gamma-cyclodextrin decreased
      the absorption of morphine. The in-vitro membrane permeation studies using
      excised rectal sacs revealed that alpha-cyclodextrin enhanced the permeation of
      morphine through the rectal membranes. In contrast, viscous polysaccharides such
      as xanthan gum retarded the plasma morphine levels after the rectal
      administration, reflecting in-vitro slow release characteristics. A combination
      of alpha-cyclodextrin and xanthan gum produced sustained plasma profiles of
      morphine along with an increased rectal bioavailability (more than 4 times). From
      the observation of the distribution behavior of suppositories in rabbit rectum
      and colon after the rectal administration, xanthan gum was found to prevent the
      upward spread of the drug. Gross and microscopic observations suggested that this
      preparation was less irritating to the rectal mucosa.

PMID- 7714738
TI  - A biophysical model of passive and polarized active transport processes in Caco-2
      cells: approaches to uncoupling apical and basolateral membrane events in the
      intact cell.
AB  - This report is aimed at the biophysical modeling of transmembrane events
      involving a passive diffusion and directional pumplike mechanism at the apical
      (AP) and basolateral (BL) membranes of cultured cell monolayers. The essence of
      the model is based on experimental evidences for the existence of a saturable,
      apically polarized transport system in Caco-2 cells for peptides which hindered
      apical to basolateral flux, enhanced basolateral to apical flux, and showed
      substrate specificity. This system was further inhibited by verapamil, suggesting
      some homology with P-glycoprotein, the principal mediator of drug resistance in
      multidrug resistant cancer cells. Preliminary evidence was also obtained
      suggesting an additional polarized uptake system for the same peptides in the
      basolateral membrane. Upon saturation and/or inhibition of the active transport
      mechanisms with verapamil, the peptide fluxes in apical-to-basolateral direction
      and the basolateral-to-apical direction converged and became controlled by the
      passive mechanism. Since the intent of the modeling was to provide useful
      templates for the design of probing experiments and to delineate and quantify
      mass transfer mechanisms at the AP and BL membranes and their interrelationships,
      theoretical equations were developed for a host of kinetic boundary conditions:
      (a) AP-->BL and BL-->AP transfluxes, (b) bidirectional effluxes from substrate
      preloaded cells, (c) undirectional efflux across the AP or BL membrane from
      preloaded cells, and (d) uptake kinetics via the AP or BL membrane leading to
      equilibrium. Furthermore, flux expressions were reduced to membrane permeability
      coefficients to accommodate passive diffusion, saturation, inhibition, and
      directionality. The diffusional mass transport resistances of the aqueous
      boundary layers and microporous filter support of the cell monolayer were
      necessarily included.

PMID- 7714740
TI  - Determination of a quaternary mixture of vitamins B6, B1, and B12 and uridine 5'
      triphosphate, by derivative spectrophotometry.
AB  - A new method for determining a quaternary mixture of vitamins B6, B1, and B12 and
      uridine 5'-triphosphate (UPT) using second-derivative spectrophotometry is
      described. Calibration graphs were linear up to 30 micrograms/mL of vitamin B6 at
      307 nm (r = 0.9999) and vitamin B1 at 282.7 nm (r = 0.9997) and up to 35
      micrograms/mL of vitamin B12 at 360.5-374 nm, peak-to-peak (r = 0.9999), and UTP
      at 261 nm (r = 1.0000). Detection limits at the p = 0.05 level of significance
      were calculated to be 0.20, 0.46, 0.22, and 0.20 microgram/mL for vitamins B6,
      B1, and B12 and UTP, respectively. An exhaustive statistical analysis of the
      experimental data was performed to confirm the validity of the method. The
      procedure does not require any separation step or solving of equations. The
      method was successfully applied for determining synthetic mixtures and commercial
      injections for these drugs.

PMID- 7714739
TI  - Physical stabilization of insulin by glycosylation.
AB  - The modification of human insulin by the covalent attachment of monosaccharide
      moieties to insulin amino group(s) alters the aggregation and self-association
      behavior, improving both the pharmaceutical stability and biological response.
      The synthesis of p-succinamidophenyl glucopyranoside-insulin conjugate(s) (SAPG
      insulin) has resulted in seven possible glucosylated insulin derivatives (three
      monosubstituted, three disubstituted, and one trisubstituted). These derivatives
      were isolated and purified using ion exchange chromatography. Characterization of
      the derivatives includes determining the site and number of sugar groups attached
      for each individual derivative and an evaluation of biological activity. Nearly
      all the derivatives retained in vivo biological activity comparable to insulin.
      In addition, extensive physicochemical characterization of the glucosylated
      insulin derivatives was undertaken to determine association/aggregation
      properties using GPC, dynamic light scattering, UV/Vis, and CD spectroscopy.
      Protein self-association was most suppressed with the disubstituted derivatives,
      especially those substituted on PheB1, and the trisubstituted derivative. The
      same general pattern was observed for physical stability of glucosylated insulin
      derivatives. As the number of glucosyl moieties attached to insulin increased,
      solution physical stability dramatically improved. Yet, the most significant
      impact to stability was glycosylation at the PheB1 site.

PMID- 7714741
TI  - Efficacy of a 3-substituted versus 17-substituted chemical delivery system for
      estradiol brain targeting.
AB  - Brain-targeted delivery of estrogens has been achieved by a chemical delivery
      system (CDS) in which a molecular targetor (1-methyl-1,4-dihydronicotinate) was
      attached to the 17-alcohol of estradiol. Optimization of this effect was
      attempted with the isomeric 3-phenol ester. Estradiol 3-nicotinate was prepared
      with nicotinic anhydride, which selectively acylated the phenol position.
      Methylation and reduction gave estradiol 3-(1-methyl-1,4-dihydronicotinate) of
      the 3-E2-CDS. Theoretical and electrochemical investigation indicated that the 3
      E2-CDS was more stable to oxidation than was the prototype 17-ester (17-E2-CDS).
      Systemic administration of the 17-E2-CDS produced high levels of the
      corresponding quaternary salt in the brain of rats, which disappeared with an
      estimated half-life of > 2 days, but 3-E2-CDS dosing resulted in no significant
      quaternary salt trapping. Pharmacological activity was potent and sustained after
      17-E2-CDS dosing but transient after 3-E2-CDS administration. Thus, the 3-E2-CDS
      reduced the rate of weight gain in male rats but to a lesser extent and for a
      shorter duration than did the 17-E2-CDS. Similar effects were seen on pituitary
      hypertrophy, reduction in serum androgen concentrations, and involution of
      prostate and seminal vesicles. The results of these studies suggest that
      placement of the targeting ester at the phenol position increases dihydropyridine
      stability but, at the same time, reduces brain sequestration.

PMID- 7714742
TI  - Intestinal absorption of dideoxynucleosides: characterization using a multiloop
      in situ technique.
AB  - The intestinal absorption of dideoxynucleosides was studied in rabbits, using a
      closed-loop mesenteric-sampling in situ technique developed in this laboratory,
      and the kinetic profiles were characterized. Each of the dideoxynucleosides
      exhibited different dependence on the intestinal regions studied: 3'-azido-2',3'
      dideoxythymidine was best absorbed from the ileum, while 2',3'-dideoxyinosine and
      2',3'-dideoxycytidine were preferentially absorbed from the jejunum. The results
      were validated by the mass-balance approach; the percent of drug retained in the
      intestinal lumen and that degraded at the intestinal pH, by colonic flora, in the
      intestinal tissue, and in plasma were assessed.

PMID- 7714743
TI  - Absorption of transdermally delivered ketorolac acid in humans.
AB  - Transdermal delivery of ketorolac acid, a potent analgesic, through human skin in
      vitro and in vivo was evaluated. The following three transdermal solutions were
      selected to study the in vitro skin permeation rate of ketorolac acid:
      formulation A, isopropyl alcohol: water: isopropyl myristate (IPA/water/IPM;
      11:7:1); formulation B, ethanol: propylene glycol:isopropyl myristate (ET/PG/IPM;
      11:7:2); and formulation C, IPM/capmul (glyceryl mono- and dicaprylate;
      Monoctanoin). The permeation of ketorolac acid through cadaver skin from a
      saturated drug solution was evaluated at 32 degrees C with a modified Franz
      diffusion cell. The in vitro skin fluxes were 180, 177, and 14 micrograms/cm2/h
      for formulations A, B, and C, respectively. The systemic bioavailability of
      ketorolac acid from three transdermal formulations was evaluated in nine healthy
      subjects in a randomized three-way crossover fashion. Hill Top chambers were used
      as prototype dermal delivery devices to load the drug solution. This procedure
      was followed by the immediate application of devices to human subjects for 24 h.
      Blood samples were collected at various time intervals up to 48 h, and the
      samples were assayed by HPLC. The basic pharmacokinetic parameters were derived
      from the drug plasma concentration versus time plot. The maximum drug plasma
      concentrations were 1.265, 0.696, and 0.092 micrograms/mL for formulations A, B,
      and C, respectively. Formulation A provided the highest in vitro and in vivo
      transdermal delivery rate among the three formulations studied. An excellent
      correlation between the in vitro steady-state skin flux and the area under the
      curve of in vivo plasma drug concentration versus time was observed for all the
      three formulations.

PMID- 7714744
TI  - Potentiometric determination of the partition and distribution coefficients of
      dianionic compounds.
AB  - The potentiometric determination of the partition and distribution coefficients
      of two dianionic hexapeptide derivatives is described. For each of these
      compounds, the partition coefficient of the dianion makes the largest
      contribution to the distribution coefficient at pH 7.4.

PMID- 7714745
TI  - In vitro characterization of sodium glycocholate binding to cholestyramine resin.
AB  - Cholestyramine resin in a bile acid sequestrant which binds with bile salts in
      the intestinal lumen to increase the fecal excretion of bile salts and, thus,
      lower blood serum cholesterol. In order to gain a better understanding of the low
      in vivo potency of cholestyramine, in vitro equilibrium binding studies, water
      sorption studies, and resin capacity measurements were performed using
      cholestyramine and the bile salt sodium glycocholate. Equilibrium binding and
      water sorption studies entailed equilibrating cholestyramine (1.0-20 mg/mL) with
      solutions which varied in glycocholate anion concentration (0.20-16.5 mM) and
      chloride anion concentration (15-150 mM). The resin's practical specific capacity
      for glycocholate was lower than the practical specific capacity for chloride.
      This difference suggests that the rigid, bulky bile salt was pore excluded from
      10% of the resin's ionogentic sites. A fundamental parameter called the capacity
      corrected molar selectivity coefficient, KGC-Cl-, was postulated to describe the
      underlying binding phenomena and was determined by measuring the free
      glycocholate and chloride anion concentrations; KGC-Cl- ranged from 9.8 (+/- 0.7)
      to 18.6 (+/- 0.2) and depended on the square of the free chloride concentration.
      The capacity-corrected molar selectivity coefficient was larger than the molar
      selectivity coefficient due to pore exclusion of glycocholate. A more simple
      method to calculate the capacity-corrected molar selectivity coefficient which
      required less data gave similar values to the more rigorous method (r2 = 0.955).

PMID- 7714746
TI  - Nasal mucosal metabolism and absorption of pentapeptide enkephalin analogs having
      varying N-terminal amino acids.
AB  - A series of enkephalin analogs with varying amino acids on the N-terminus were
      synthesized and evaluated in rats in situ for their hydrolytic stability and
      absorption when administered nasally. The amino acids on the N-terminus were
      tyrosine (Y), alanine (A), serine (S), lysine (K), and aspartic acid (D). These
      amino acids represent different charges and sizes. Among these peptides, only the
      peptide carrying aspartic acid on the N-terminus was stable. The rank order of
      degradation rates was YGGFL > AGGFL > SGGFL, KGGFL > DGGFL. These results suggest
      that there are relatively high activities of aminopeptidases N and B and
      relatively low activity of aminopeptidase A in the rat nasal mucosa. Absorption
      studies were performed to determine the absorption rate of DGGFL, by measuring
      percentage recovery of nasal doses vs time. After a 50 microL dose of a 3 mg/mL
      solution, this peptide exhibited an absorption half-life of 21 min, which is
      similar to the nasal absorption rate of YGGFL.

PMID- 7714748
TI  - Accuracy of numerical inversion of Laplace transforms for pharmacokinetic
      parameter estimation.
AB  - Numerical inversion of the Laplace transform is a useful technique for
      pharmacokinetic modeling and parameter estimation when the model equations can be
      solved in the Laplace domain but the solutions cannot be inverted back to the
      time domain. The accuracy of numerical inversion of the Laplace transform using
      an infinite series approximation due to Hosono was systematically studied by
      reference to 17 widely differing functions having known inverse transforms. The
      error of inversion was found to be very sensitive to the details of the computer
      implementation of the method; for example, double-precision artihmetic is
      essential. The method used to sum the series in the least-squares program
      Multi(Filt) was often unable to achieve a relative error of less than 10(-4), and
      a Monte Carlo simulation showed that this method is insufficiently accurate for
      reliable least-squares parameter estimation. Improvements to the algorithm are
      described whereby a better method of applying Euler's transformation is used and
      the number of terms summed is determined automatically by the rate of convergence
      of the series. The improved algorithm is more efficient in inverting easy
      functions and more reliable in inverting difficult functions, especially those
      involving a time lag. With its use, pharmacokinetic parameter estimation can be
      performed with essentially the same accuracy as when the function is defined in
      the time domain.

PMID- 7714747
TI  - Use of C1300 neuroblastoma cells to evaluate the protective value of
      hexamethonium, trimethaphan, hemicholinium, and triethylcholine against
      diisopropyl phosphorofluoridate toxicity.
AB  - Our intent was to evaluate the C1300 neuroblastoma cell as an in vitro system for
      studying the mode of action and efficacy of drugs used to treat or prevent
      organophosphate intoxication. The anticholinergic drugs hexamethonium,
      trimethaphan, and hemocholinium and the triethylcholine and
      cholinesterase/reactivator 2-pyridine aldoxime methochloride (2-PAM) have been
      shown to be effective in preventing intoxication by diisopropyl
      phosphorofluoridate (also known as diisopropyl fluorophosphate, DFP) in vivo. We
      determined their efficacy in preventing cell death (as measured by trypan blue
      exclusion) of neuroblastoma cells alone or in combination. We also determined
      their efficacy in reversing the cytotoxic effects of DFP on cell DNA synthesis
      (as measured by [3H]-thymidine incorporation), cell RNA synthesis (as measured by
      [3H]uridine incorporation), and on cell protein synthesis (as measured by
      [3H]leucine incorporation). The maximal nontoxic doses of the drugs in vitro were
      determined. All anticholinergic agents studied reduced the cytotoxicity of DFP
      using one or more parameters. 2-PAM, the cholinesterase reactivator, enhanced the
      cytotoxicity of DFP on cultured cells at a high concentration (1 mg/mL) and
      reduced it at a lower concentration (0.3 mg/mL). All four anticholinergic agents
      were capable of enhancing the uptake of [3H]thymidine. Only hexamethonium and
      hemicholinium reversed DFP inhibition of DNA synthesis. RNA synthesis was not
      affected by any anticholinergic agent and no agent reversed DFP inhibition of RNA
      synthesis. Protein synthesis was enhanced by every anticholinergic agent except
      hemicholinium; the inhibition of protein synthesis by DFP was reversed by
      trimethaphan and triethylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714749
TI  - Spinal controlled delivery of bupivacaine from DL-lactic acid oligomer
      microspheres.
AB  - Bupivacaine-loaded microspheres made from DL-polylactic acid oligomers of
      different molecular weights (MW 2000 and 9000 g/mol, named PLA 2000 and PLA 9000,
      respectively) which displayed different in vitro release profiles were
      administered via the spinal route to rabbits. In comparison to the drug
      administered as a solution (2 mg as equivalent base), PLA 2000 and PLA 9000
      microspheres (10 mg as equivalent base) led to a slower uptake of the drug in the
      systemic circulation, as suggested by the mean maximal plasma concentrations: 326
      +/- 81, 321 +/- 57 and 64 +/- 54 ng/mL, respectively. Pharmacodynamic evaluation
      of the anesthetic action, by means of intensity and time course of motor
      blockade, indicated a sustained release. In comparison to the drug solution, the
      PLA 2000 microspheres led to an increase duration of median maximal blockade (172
      min versus 44.5 min). The PLA 9000 microspheres failed to reach maximal blockade
      as a result of a too low release rate.

PMID- 7714750
TI  - Isomeric benzoylpyrroleacetic acids: some structural aspects for aldose reductase
      inhibitory and anti-inflammatory activities.
AB  - A number of isomeric benzoylpyrroleacetic acids (1-6) were prepared and tested in
      vitro for rat lenses aldose reductase activity. These pyrrole derivatives are
      structurally related to the acidic nonsteroidal anti-inflammatory drugs.
      Therefore, their anti-inflammatory properties were also evaluated in the
      carrageenan-induced rat paw edema model. Inhibition of the aldose reductase
      enzyme was found to depend on the presence of both the benzoyl and acetic acid
      functionalities. Better activity resulted when these moieties were introduced at
      positions 1 and 3 of the pyrrole ring. However, for anti-inflammatory activity,
      the acetic acid group was not necessary and, in some cases, its presence resulted
      in a loss of activity. 3-Benzoylpyrrole-1-acetic acid (6) exhibited an IC50 of
      2.5 microM in the aldose reductase assay which is comparable to that of
      alrestatin (1.5 microM). Compound 6, however, showed no anti-inflammatory
      activity at doses up to a 100 mg/kg, ip, in the rat paw model.

PMID- 7714751
TI  - Atom/fragment contribution method for estimating octanol-water partition
      coefficients.
AB  - Atom/fragment contribution values, used to estimate the log octanol-water
      partition coefficient (log P) of organic compounds, have been determined for 130
      simple chemical substructures by a multiple linear regression of 1120 compounds
      with measured log P values. An additional 1231 compounds were used to determine
      235 "correction factors" for various substructure orientations. The log P of a
      compound is estimated by simply summing all atom/fragment contribution values and
      correction factors occurring in a chemical structure. For the 2351 compound
      training set, the correlation coefficient (r2) for the estimated vs measured log
      P values is 0.98 with a standard deviation (SD) of 0.22 and an absolute mean
      error (ME) of 0.16 log units. This atom/fragment contribution (AFC) method was
      then tested on a separate validation set of 6055 measured log P values that were
      not used to derive the methodology and yielded an r2 of 0.943, an SD of 0.408,
      and an ME of 0.31. The method is able to predict log P within +/- 0.8 log units
      for over 96% of the experimental dataset of 8406 compounds. Because of the simple
      atom/fragment methodology, "missing fragments" (a problem encountered in other
      methods) do not occur in the AFC method. Statistically, it is superior to other
      comprehensive estimation methods.

PMID- 7714752
TI  - Plasma concentrations and pharmacokinetic parameters of nitrofenac using a simple
      and sensitive HPLC method.
AB  - An accurate and sensitive HPLC method has been developed for the determination of
      nitrofenac, a new, original diclofenac derivate showing a good tolerability and a
      wide anti-inflammatory profile, diclofenac, and its metabolites in plasma. This
      method has been applied to evaluate the pharmacokinetic parameters of the drugs,
      using a noncompartmental model, after the oral administration of 5 mg/kg
      nitrofenac to rats. Nitrofenac and the internal standard flufenamic acid were
      dissolved in acetonitrile, and diclofenac was dissolved in methanol. The drugs
      were eluted from a 5 microns LC-8 column with a mobile phase consisting of
      acetonitrile/water (50/50 v/v) adjusted to pH 3.3 with glacial acetic acid, at a
      flow rate of 2 mL/min with UV detection at 280 nm for diclofenac and 275 nm for
      nitrofenac. The detection limit for the drugs in plasma was 25 ng/mL. The peak
      concentration of nitrofenac was reached 7 h after drug administration, while with
      diclofenac we observed three peaks at 2, 5, and 10 h; the mean residence time and
      the elimination rate constant for nitrofenac were 6.18 +/- 0.09 h and 0.37 +/-
      0.03 h-1 respectively, while those for diclofenac were 12.24 +/- 0.11 h and 0.11
      +/- 0.04 h-1. Under our conditions, the metabolism of nitrofenac produced 23%
      diclofenac and other metabolites: the plasma concentrations and kinetic
      characteristics of diclofenac are enough to induce an anti-inflammatory activity,
      while the clinical importance of the other metabolites remains to be elucidated.

PMID- 7714753
TI  - Prodrugs of vitamin E. 1. Preparation and enzymatic hydrolysis of
      aminoalkanecarboxylic acid esters of d-alpha-tocopherol.
AB  - Nine aminoalkanecarboxylic acid esters of d-alpha-tocopherol were synthesized and
      evaluated as potential water-soluble prodrugs suitable for parenteral
      administration. The hydrochloric acid salts of the esters were soluble in water.
      The kinetics of hydrolysis of the esters was studied in isotonic phosphate
      buffer, rat plasma, human plasma, and rat liver homogenate at 37 degrees C. The
      hydrolysis of the esters was proved to be catalyzed by liver esterases. The
      susceptibility of the esters to undergo liver esterase hydrolysis was affected by
      the structure of the amino functionality and size of the acyl moiety on the
      promoiety. The N-methylaminoacetyl and N,N-dimethylaminoacetyl esters of d-alpha
      tocopherol were more rapidly hydrolyzed than d-alpha-tocopheryl acetate, a
      commercially available d-alpha-tocopheryl ester. These results suggested that the
      salts of the N-methylaminoacetyl and N,N-dimethylaminoacetyl esters are promising
      prodrug candidates of d-alpha-tocopheryl for parenteral use.

PMID- 7714754
TI  - Dilatation of the basilar artery in response to selective activation of
      endothelin B receptors in vivo.
AB  - The objective of this study was to examine effects of activation of endothelin
      (ET) B receptors on tone of the basilar artery in vivo. By using a cranial window
      in anesthetized rats, we examined the effects of IRL 1620, a selective ETB
      receptor agonist, on diameter of the basilar artery. Under control conditions,
      diameter of the basilar artery was 214 +/- 6 microns (mean +/- S.E.). Topical
      application of IRL 1620 (10(-8) mol/l) for 4 min dilated the basilar artery by 30
      +/- 4%. Marked desensitization of vasodilator responses was observed in response
      to a second application of IRL 1620, but not acetylcholine, which indicates a
      homologous nature of desensitization. REA/001, an ETA/ETB receptor antagonist,
      abolished IRL 1620-induced dilatation of the basilar artery. BQ 123, a selective
      ETA receptor antagonist, inhibited constriction in response to ET-1, but did not
      affect dilator responses of the basilar artery to IRL 1620. Both NG-nitro-L
      arginine methyl ester and NG-nitro-L-arginine, inhibitors of nitric oxide
      synthase, produced marked inhibition of dilator responses of the basilar artery
      to IRL 1620 without inhibiting vasodilator responses to sodium nitroprusside.
      Indomethacin did not inhibit vasodilatation in response to IRL 1620. These
      findings suggest that activation of ETB receptors produces dilatation of the
      basilar artery in vivo. Dilator responses of the basilar artery to activation of
      ETB receptors are dependent on production of nitric oxide.

PMID- 7714755
TI  - (1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat
      are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5
      HT2A/2C antagonists, D1 antagonists and 5-HT1A agonists.
AB  - In this study, the involvement of serotonergic and dopaminergic receptors in the
      modulation of the head-twitch (HTW) response to the 5-hydroxytryptamine (5
      HT)2A/5-HT2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, was
      characterized in rats using novel and selective ligands at 5-HT2A, 5-HT2C, D1, D2
      and 5-HT1A receptors. HTW were dose-dependently inhibited by the 5-HT2A/2C
      antagonists, ritanserin, metergoline, mesulergine, mianserin, ICI 169,369 and LY
      58,537, by the preferential 5-HT2A antagonist, ketanserin and by the novel,
      selective 5-HT2A antagonist, SR 46349B. A further selective 5-HT2A antagonist,
      MDL 100,907, very potently abolished HTW (ED50 = 0.005 mg/kg). The order of
      relative potency correlated highly with their affinity at 5-HT2A (r = 0.83) but
      not 5-HT2C receptors (r = 0.06). In addition, the novel, selective 5-HT2C
      antagonist, SB 200,646A, failed to abolish HTW and the 5-HT2C agonists/5-HT2A
      antagonists, 1-(3-chlorophenyl)piperazine and 1-(3
      trifluoromethylphenyl)piperazine, blocked, rather than elicited, HTW. The D1
      antagonists, SCH 23390, NNC 112, NNC 756, SCH 39166 and A 69024, in this order of
      relative potency that correlated with their affinity at D1 receptors (r = 0.98),
      blocked HTW. The D2 antagonists, raclopride, eticlopride and haloperidol also
      blocked HTW. The 5-HT1A agonists, S 14671, S 14506, 8-hydroxy-2-(di-n
      propylamino)tetralin, buspirone, ipsapirone and (+)-flesinoxan, abolished HTW.
      The action of 8-hydroxy-2-(di-n-propylamino)tetralin was blocked by (-)
      tertatolol (ID50 = 4.5 mg/kg), a novel 5-HT1A receptor antagonist. Similarly, (-)
      tertatolol attenuated the action of S 14506 and abolished that of S 14671,
      buspirone and ipsapirone. A role of postsynaptic 5-HT1A receptors in the action
      of 5-HT1A agonists was suggested by the finding that parachlorophenylalanine (3 x
      300 mg/kg, i.p.), which depleted cerebral pools of 5-HT, did not modify the
      activity of ipsapirone. The present data demonstrate that 5-HT2A receptors
      mediate HTW in rats and that both D1 and D2 receptors as well as (postsynaptic) 5
      HT1A receptors play a role in their expression.

PMID- 7714756
TI  - In vitro and in vivo testing of hydralazine genotoxicity.
AB  - Hydralazine (HDZ), a p.o. effective antihypertensive drug, was evaluated for its
      genotoxic effects in both rodent and human cultured cells and in the intact rat.
      Dose-dependent amounts of DNA fragmentation, as measured by the alkaline elution
      technique, and of DNA repair synthesis, as revealed by autoradiography, were
      produced in primary cultures of metabolically competent rat hepatocytes by
      subtoxic HDZ concentrations ranging from 0.32 to 1.0 mM. A similar potency in
      inducing DNA repair synthesis was displayed by HDZ in primary cultures of
      hepatocytes from four human donors. A modest reduction of both DNA fragmentation
      (-13%) and DNA repair (approximately -50%) was observed in hepatocytes obtained
      from rats pretreated with indomethacin in order to reduce prostaglandin
      synthetase activity. In contrast, neither in rat nor in human hepatocytes,
      differences in N-acetyltransferase activity resulted in meaningful changes of the
      same end points. V79 cells, which are essentially deficient of monooxygenases
      catalyzing the biotransformation of xenobiotics, were as sensitive as hepatocytes
      to the DNA-damaging activity of HDZ. Moreover, after exposure to 0.1 to 0.3 mM
      HDZ, a modest (2.1- to 2.8-fold), but significant, increase in the frequency of
      mutation to 6-thioguanine resistance was observed in V79 cells in the absence of
      a metabolic activation system. In rats, a single p.o. dose of 80 mg/kg produced a
      clastogenic effect in the liver, but not in the bone marrow, and the p.o.
      administration for 14 successive days of approximately 46 mg/kg/day increased the
      average diameter of liver basophilic foci initiated by
      diethylnitrosamine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714758
TI  - Involvement of monoamine uptake inhibition and local anesthesia in the
      cardiovascular response to cocaine in conscious rabbits.
AB  - The cardiovascular effect of cocaine in rabbits was examined for peripheral and
      central components and for the contribution of the primary actions of cocaine,
      i.e., inhibition of the high affinity uptake mechanisms for monoamines and local
      anesthesia. In pithed rabbits with electrically stimulated sympathetic outflow (2
      Hz), cocaine (0.2-5 mg kg-1) lowered the clearance of [3H]norepinephrine from
      plasma and increased the plasma norepinephrine concentration. Cocaine (0.2 and 1
      mg kg-1) increased blood pressure and heart rate, whereas after 5 mg kg-1 heart
      rate and blood pressure decreased briefly and then recovered. In conscious
      rabbits, cocaine (0.2 and 1 mg kg-1) reduced renal sympathetic nerve activity and
      tended to reduce blood pressure and heart rate. Cocaine (5 mg kg-1) increased
      sympathetic nerve activity, blood pressure and the plasma norepinephrine and
      epinephrine concentrations. The effects of the lower doses were abolished in
      animals pretreated with oxaprotiline, but were not changed in animals pretreated
      with fluvoxamine or SCH 23390 (R-(+)-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3
      benzazepin-7-ol) + sulpiride. The effects of cocaine (5 mg kg-1) were attenuated
      by SCH 23390 + sulpiride but were not changed after oxaprotiline or fluvoxamine.
      Procaine (15 mg kg-1) mimicked the effects of cocaine (5 mg kg-1) on blood
      pressure and renal sympathetic nerve activity. Blood pressure also was increased
      by lidocaine (6 mg kg-1). It is concluded that cocaine enhances peripheral
      sympathetic neuro-effector transmission. In conscious rabbits, however, low doses
      fail to raise blood pressure because they simultaneously depress central
      sympathetic tone by blockade of the uptake of norepinephrine in the central
      nervous system. High cocaine doses cause sympathoexcitation in conscious rabbits.
      The mechanism seems to be dual: blockade of dopamine uptake in the central
      nervous system and a (peripheral or central) local anesthetic action.

PMID- 7714757
TI  - Pharmacokinetic interaction between isradipine and lovastatin in normal, female
      and male volunteers.
AB  - We have examined the pharmacokinetic interaction between isradipine and
      lovastatin in six male and six female, healthy, normotensive, human subjects
      after a single dose and after treatment for 5 days. The isradipine plasma
      concentrations were determined by a radioimmunoassay and the lovastatin serum
      concentrations by gas chromatography-mass spectrometry (GC/MS) and by the
      inhibition of the 3-hydroxy-3-methylglutaric-coenzyme reductase activity. We
      found that the apparent serum concentrations of lovastatin were 4- to 6-fold
      higher in the reductase-inhibition assay than the GC/MS assay, suggesting that
      the bulk of the reductase inhibition is due to active metabolites. The peak and
      the time-to-peak concentrations were unaffected by the treatments, either after
      the first dose or after continued administration. In male subjects, after
      repeated doses of isradipine, the lovastatin area under the time-concentration
      curves (AUCs) decreased by 40% as determined by the GC/MS assay (P < .001) and
      20% as determined by the reductase-inhibition assay (P < .0022). In the female
      subjects, isradipine treatment decreased the lovastatin AUCs as determined by the
      GC/MS assay, but this was not statistically significant due to a high variance.
      Furthermore, in the female subjects, isradipine had no effect on the lovastatin
      AUCs as determined by the reductase-inhibition assay. Because the lovastatin peak
      and the time-to-peak concentrations were unaffected by isradipine treatment, the
      decreased lovastatin AUCs were probably not due to altered intestinal absorption.
      More likely, because lovastatin has a high hepatic clearance, the decreased AUCs
      seen after isradipine treatment could be due to increases in the clearance of
      lovastatin secondary to increased hepatic blood flow.

PMID- 7714759
TI  - Pharmacological analysis of the scratching produced by dopamine D2 agonists in
      squirrel monkeys.
AB  - Several dopamine agonists, administered i.m., produced persistent, excessive and
      non-localized scratching in squirrel monkeys (Saimiri sciureus). Studies were
      conducted with a series of drugs to determine the pharmacological mechanisms
      responsible for this effect. All of the dopamine D2 agonists studied produced
      dose-related increases in scratching, whereas several dopamine D1 receptor
      agonists, indirect dopamine agonists and drugs acting on other receptors failed
      to produce dose-related increases in scratching. The scratching produced by D2
      agonists was stereospecific; (-)-NPA produced scratching whereas its (+)
      enantiomer was inactive up to doses 300-fold higher. Scratching induced by
      quinpirole was attenuated by both D2 and D1 antagonists, and this antagonism was
      stereospecific, with the D2 antagonist (-)-eticlopride, but not its enantiomer,
      active. Sensitivity developed to the effects of D2 agonists with the quinpirole
      dose-effect curve shifting to the left by a factor of approximately 64. Two
      partial D2 receptor agonists (SDZ 208-911 and SDZ 208-912) had limited efficacy
      in producing scratching, however, one partial D2 receptor agonist (terguride) was
      fully efficacious, suggesting that there are spare receptors for this effect. The
      peripherally active dopamine antagonist domperidone and the histamine antagonist
      diphenhydramine also reduced the scratching induced by D2 agonists, but not to
      the same extent as centrally acting D2 antagonists. Scratching in squirrel
      monkeys is an effect that appears to be due to agonist actions at D2 receptors,
      and may be mediated by a release of histamine. This behavioral activity may be
      useful as an in vivo indication of D2 receptor activity in primates.

PMID- 7714760
TI  - Organic anion transport in rabbit renal basolateral membrane vesicles.
AB  - Pathways for p-aminohippurate (PAH) transport across the basolateral membrane of
      rabbit proximal tubule cells were investigated from studies of [3H] PAH uptake in
      membrane vesicles isolated by Percoll-density gradient centrifugation. The 10-s
      uptake of PAH was not significantly different when measured in the absence of
      cation gradients or in the presence of inwardly directed Na, Li, K or choline
      gradients that suggests the absence of a mechanism mediating Na-PAH cotransport.
      A probenicid-sensitive, trans-stimulation of [3H] PAH uptake was observed in the
      presence of an outward PAH gradient. PAH gradient-driven [3H] PAH uptake was cis
      inhibited by glutarate, alpha-ketoglutarate, adipate and sebacate and outward
      gradients of alpha-ketoglutarate trans-stimulated probenicid-sensitive PAH
      uptake. A concentrative accumulation of PAH was measured in the presence of an
      inward Na gradient and the dicarboxylates glutarate or alpha-ketoglutarate.
      Compared to the absence of a pH gradient, an inside alkaline pH gradient induced
      an increased PAH uptake both in the presence and absence of CO2/HCO3. Inside
      negative and inside-positive voltage differences were observed to stimulate and
      inhibit alpha-ketoglutarate gradient-driven PAH uptake, respectively. alpha
      Ketoglutarate gradient-driven PAH uptake was progressively reduced in the
      presence of increasing penicillin concentration and an outward gradient of alpha
      ketoglutarate induced an increased level of [14C] penicillin uptake. These
      results suggest the presence of a probenicid-sensitive organic anion exchange
      mechanism as a pathway for PAH and penicillin transport across the basolateral
      membrane of rabbit proximal tubule cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714761
TI  - Relative potency and arteriovenous selectivity of nitrovasodilators on human
      blood vessels: an insight into the targeting of nitric oxide delivery.
AB  - The arteriovenous potency of sodium nitroprusside (SNP), linsidomine (SIN-1) and
      S-nitrosoglutathione (GSNO) was determined in human capacitance (veins) and
      resistance (arterioles) vessels in vitro and in vivo and compared with the
      venoselective nitrovasodilator nitroglycerin (GTN). Concentration-response curves
      were constructed to GTN, SNP, GSNO and SIN-1 (0.001-10 microM) in preconstricted
      human saphenous vein and to GTN, GSNO and SIN-1 (0.001-10 microM) in omental
      resistance vessels. In vivo the dilator responses of the dorsal hand vein and the
      forearm resistance bed were recorded during local infusions of GTN, SNP, GSNO and
      SIN-1 (1 pmol/min to 160 nmol/min). SNP and SIN-1 had similar arteriovenous
      profiles to that of GTN. SNP was equipotent with GTN in arterioles and veins but
      SIN-1 was 10-fold less potent than GTN in vitro and 100-fold less potent in vivo;
      the potency of SIN-1 was increased after incubation of saphenous vein with
      superoxide dismutase. GSNO was equipotent with GTN in arterioles but 10-fold less
      potent in veins in vitro and in vivo. These results demonstrate that most
      nitrovasodilators are venoselective irrespective of their mechanism of
      biotransformation to nitric oxide (NO) and suggests that NO itself might be
      venoselective in vivo. Endogenous carrier molecules, including glutathione, could
      alter the vascular profile of NO with physiological and therapeutic implications.

PMID- 7714762
TI  - Superactive lipophilic peptides discriminate multiple vasoactive intestinal
      peptide receptors.
AB  - To distinguish vasoactive intestinal peptide (VIP) receptors in the brain
      mediating neurotransmission and neurotrophism, potent VIP analogues were
      designed. Using a single amino acid substitution and the addition of a fatty acyl
      moiety, an analogue was devised that exhibited both a 100-fold greater potency
      than VIP and specificity for a VIP receptor associated with neuronal survival.
      This VIP agonist increased neuronal survival via a cAMP-independent mechanism.
      Identical chemical modification of a prototype VIP antagonist (Met-Hybrid,
      Neurotensin6-11-VIP7-28) also resulted in a 100-fold greater potency in blocking
      VIP-mediated increases in neuronal survival. Blockade of circadian activity
      rhythms was limited to VIP antagonists that could inhibit VIP-mediated increases
      in cAMP. These lipophilic peptides provide novel tools in receptor discrimination
      and drug design.

PMID- 7714763
TI  - Cardiac electrophysiologic and antiarrhythmic actions of tedisamil.
AB  - The Class III electrophysiologic and antiarrhythmic actions of the bradycardic
      agent tedisamil were assessed in vitro and in vivo. In ferret isolated right
      ventricular papillary muscles, tedisamil increased effective refractory period
      (ERP) in a concentration-dependent manner, with a 25% ERP increase achieved with
      3.0 microM tedisamil, and a 133.4% +/- 28.8% increase in ERP achieved at the high
      100 microM concentration tested. In anesthetized dogs, the cumulative i.v.
      administration of tedisamil significantly increased ventricular relative
      refractory period (VRRP) and ventricular effective refractory period (VERP) as
      well as electrocardiographic QTc intervals (100-1000 micrograms/kg i.v.). A
      20msec increase in VRRP was achieved with 45.0 micrograms/kg i.v. tedisamil, and
      a 56.1 +/- 9.8 msec (40.1% +/- 8.1%) increase in VRRP was achieved at the highest
      dose tested (1000 micrograms/kg i.v.). In the same dosage range in anesthetized
      dogs, tedisamil produced significant hemodynamic effects, including reduction in
      HR (100-1000 micrograms/kg i.v.) and elevations in mean arterial pressure (1000
      micrograms/kg i.v.), left ventricular developed pressure (1000 micrograms/kg
      i.v.) and the maximum rate of LV pressure development (100-1000 micrograms/kg
      i.v.). In anesthetized dogs studied chronically (8.2 +/- 0.6 days) after anterior
      myocardial infarction, tedisamil suppressed programmed stimulation-induced
      ventricular tachyarrhythmias (8/10, 80% suppression at 100-1000 micrograms/kg
      i.v.) and reduced the incidence of lethal ischemic arrhythmias developing in
      response to acute posterolateral myocardial ischemia (arrhythmic mortality 5/10,
      50% tedisamil vs. 34/40, 85% vehicle control cohort; P = .027). The latter
      findings suggest that tedisamil might be useful in the prevention of malignant
      ventricular arrhythmias in the setting of myocardial ischemic injury.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7714764
TI  - The in vitro and in vivo pharmacologic activity of the potent and selective
      leukotriene B4 receptor antagonist CP-105696.
AB  - CP-105696, (+)-1-(3S,4R)-[3-(4-phenyl-benzyl)-4-hydroxy-chroman-7-yl]
      cyclopentane carboxylic acid, is a structurally novel, selective and potent
      leukotriene B4 (LTB4) receptor antagonist. In vitro, CP-105696 inhibited [3H]LTB4
      (0.3 nM) binding to high-affinity LTB4 receptors on human neutrophils with an
      IC50 value of 8.42 +/- 0.26 nM. Scatchard analyses of [3H]LTB4 binding to these
      high-affinity receptors indicated that CP-105696 acted as a noncompetitive
      antagonist. CP-105696 inhibited human neutrophil chemotaxis mediated by LTB4 (5
      nM) in a noncompetitive manner with an IC50 value of 5.0 +/- 2.0 nM. Scatchard
      analyses of [3H]LTB4 binding to low-affinity receptors on neutrophils indicated
      that CP-105696 acted as a competitive antagonist at this receptor, and inhibition
      of LTB4-mediated CD11b upregulation on human neutrophils was competitively
      inhibited by CP-105696 (pA2 = 8.03 +/- 0.19). CP-105696 at 10 microM did not
      inhibit either human neutrophil chemotaxis or CD11b upregulation mediated through
      alternate (i.e., C5a, IL-8, PAF) G-protein coupled chemotactic factor receptors.
      In isolated human monocytes, LTB4 (5 nM)-mediated Ca++ mobilization was inhibited
      by CP-105696 with an IC50 value of 940 +/- 70 nM. In vivo, after oral
      administration, CP-105696 blocked neutrophil and eosinophil infiltration in
      cavine dermis mediated by either LTB4 or arachidonic acid with ED50 values of 0.3
      +/- 0.1 mg/kg. 12(R)-Hydroxyeicosatetraenoic acid-mediated neutrophil
      infiltration was blocked by 76.4 +/- 14.8% at 3 mg/kg.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7714766
TI  - Activated recombinant human protein C does not attenuate recruitment of
      neutrophils in rat models of acute inflammation.
AB  - It has been proposed that the reduction in mortality in animal models of sepsis
      by activated protein C (APC) is mediated by an antiinflammatory property rather
      than the well-characterized anticoagulant action. Human recombinant APC was
      examined for potential antiinflammatory activity in the pentobarbital
      anesthetized rat. In the dermal reversed passive Arthus model, APC (20.0 mg/kg/h,
      i.v.) elevated clotting time 10-fold 3 h after the Arthus challenge, at which
      time, the wet-weights from Arthus dermal samples in APC rats (120.0 +/- 1.5 mg, n
      = 10) did not differ from controls (120.1 +/- 1.5 mg, n = 10) but were 30%
      heavier than remote noninflamed skin (92.0 +/- 2.0 mg, n = 10), indicating that
      APC treatment did not diminish tissue edema associated with immune-complex
      deposition. Skin-lesion myeloperoxidase (neutrophil marker enzyme) activities
      from APC rats were not significantly different from controls but was 21-fold more
      than remote noninflamed skin, indicating that APC treatment did not diminish
      dermal recruitment of neutrophils. In the intestinal ischemia/reperfusion model,
      1 h complete occlusion of the superior mesenteric artery and an additional 4 h
      reperfusion was associated with a 2.87-fold increase in lung myeloperoxidase
      activity compared to sham-operated rats. APC (1.0 mg/kg/h, i.v.) did not diminish
      the elevation in this index of lung neutrophil sequestration. In conclusion, APC
      did not produce an antiinflammatory effect in the rat models used.

PMID- 7714765
TI  - Brain and plasma levels of opioid peptides are altered in rats with thioacetamide
      induced fulminant hepatic failure: implications for the treatment of hepatic
      encephalopathy with opioid antagonists.
AB  - Although plasma levels of Met-enkephalin and beta-endorphin are elevated in
      patients suffering from liver failure, it is not known whether central nervous
      system (CNS) opioidergic neurotransmission is altered in these patients. Such
      changes may contribute to the motor dysfunction, psychiatric abnormalities and
      CNS depression observed in hepatic encephalopathy (HE). Therefore, Met- and Leu
      enkephalin, dynorphin A and beta-endorphin levels were measured in discrete brain
      regions and plasma from thioacetamide-treated rats in Stages II to IV of HE.
      Pituitary and plasma beta-endorphin, Met- and Leu-enkephalin concentrations
      increased with the severity of HE by 50 to 290%. Pituitary and brainstem
      dynorphin A levels increased whereas plasma levels decreased in rats with
      thioacetamide-induced fulminant hepatic failure. Both striatal Met- and Leu
      enkephalin levels increased and hypothalamic concentrations decreased in HE.
      Concurrent with the increase in striatal Met-enkephalin levels was a 26 to 48%
      decrease in the density of striatal and hypothalamic delta receptors. No change
      in either the density or affinity of radioligand binding to mu or delta receptors
      was observed in the CNS. Finally, administering (+/-)-naloxone (5 and 10 mg/kg)
      or (+/-)-naltrexone (5-15 mg/kg), but not (+)-naloxone (10 mg/kg), significantly
      increased the motor activity of rats with Stage III HE. Whereas elevated plasma
      levels of opioid peptides may play a role in the peripheral manifestations of
      hepatic failure (ascites and hypotension), increased CNS levels of these peptides
      may be involved in the neuropsychiatric abnormalities characteristic of HE. Thus,
      opioid antagonists may be effective in ameliorating some of the neurological
      manifestations of HE.

PMID- 7714767
TI  - Central kappa opioids blunt the renal excretory responses to volume expansion by
      a renal nerve-dependent mechanism.
AB  - Central administration of kappa opioids produce significant alteration in the
      renal excretion of sodium and water under basal conditions. To determine whether
      enhanced central kappa opioid activity alters the renal handling of sodium and
      water to an integrated physiological stimuli, we compared the renal excretory
      responses produced by acute i.v. isotonic saline volume expansion in conscious
      Sprague-Dawley rats pretreated with i.c.v. isotonic saline vehicle or the
      selective kappa opioid agonist, U-50488H. In vehicle-treated animals, isotonic
      saline volume expansion produce an increase in urine flow rate and urinary sodium
      excretion and a decrease in efferent renal sympathetic nerve activity. In
      comparison with these control responses, isotonic saline volume expansion
      produced a similar magnitude change in urine flow rate in rats pretreated i.c.v.
      with U-50488H. In contrast, the natriuretic response produced by the isotonic
      saline load was markedly blunted in these central kappa opioid-treated animals.
      Moreover, the sympathoinhibitory response characteristically produced by the
      isotonic saline volume expansion was completely prevented in animals receiving
      i.c.v. U-50488H. To elucidate further the role of the renal nerves in mediating
      this central kappa opioid-induced renal excretory response, these studies were
      repeated in chronic bilaterally renal denervated rats. The results of these
      studies demonstrated that bilateral renal denervation restored the capacity of
      i.c.v. U-50488H-pretreated rats to maximally excrete the sodium load. Together,
      these studies demonstrate that, in conscious Sprague-Dawley rats, increased
      central kappa opioid activity significantly blunts the natriuretic response to
      isotonic saline volume expansion by a renal nerve-dependent mechanism.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7714768
TI  - Verapamil attenuates calcium-induced mitochondrial swelling and respiratory
      dysfunction.
AB  - A protective effect of verapamil against hypoxic renal proximal tubule injury has
      been demonstrated in vitro. In contrast to other cytoprotective agents such as
      glycine or alanine, the protective effect of verapamil is associated with better
      maintenance of cellular ATP and potassium levels. These findings suggested a
      possible direct effect of verapamil on the mitochondria in addition to known
      effects of verapamil on membrane Ca channels. In the present study, the direct
      effects of verapamil on Ca-induced swelling, respiratory dysfunction, Ca uptake
      rate and phospholipase activity of renal cortical mitochondria were determined.
      Verapamil (100 microM) significantly inhibited Ca-induced mitochondrial swelling
      and partially prevented the associated reduction in respiratory control ratio
      (State 3/State 4: Ca + verapamil: 2.8 +/- 0.1 vs. Ca alone, 2.0 +/- 0.2; P <
      .01). A phospholipase A2 inhibitor, dibucaine (100 microM), significantly
      inhibited Ca-induced mitochondrial swelling and attenuated the decrease in
      respiratory control ratio (Ca + dibucaine: 2.9 +/- 0.1 vs. Ca alone, 2.0 +/- 0.2;
      P < .001). Neither agent, either alone or combined, completely prevented the
      respiratory dysfunction. Either verapamil or dibucaine attenuated the
      mitochondrial Ca uptake rate and reduced the rate of Ca-stimulated
      polyunsaturated free fatty acid accumulation; verapamil treatment also was
      associated with diminished net release of saturated and monounsaturated free
      fatty acids. These findings demonstrate that verapamil exerts a protective effect
      against Ca-induced mitochondrial damage which may be mediated in part by its
      effect to suppress mitochondrial Ca uptake and mitochondrial phospholipase
      activity.

PMID- 7714769
TI  - Studies of the biogenic amine transporters. V. Demonstration of two binding sites
      for the cocaine analog [125I]RTI-55 associated with the 5-HT transporter in rat
      brain membranes.
AB  - Earlier work characterized the binding of the high-affinity cocaine analog 3 beta
      (4-125iodophenyl)-tropane-2-carboxylic acid methyl ester ([125I]RTI-55) to
      membranes prepared from rat caudate. That investigation demonstrated that
      [125I]RTI-55-labeled serotonin (5-HT) transporters in addition to dopamine (DA)
      transporters and resolved [125I]RTI-55 binding to 5-HT transporters into two
      distinct components. In the present study, we characterized [125I]RTI-55 binding
      to membranes prepared from whole rat brain minus caudate. The first series of
      experiments established that [125I]RTI-55 labels both DA and 5-HT transporters
      and that 50 nM paroxetine and either 1000 nM 1-[2-(diphenylmethoxy)ethyl]-4-(3
      phenylpropyl)homopiperazine (LR1111) or 500 nM (RTI-120) could be used to block
      [125I]RTI-55 binding to the 5-HT and DA transporters, thereby generating
      selective assay conditions for the DA and 5-HT transporters, respectively.
      Selective lesioning of dopaminergic and serotonergic neurons with
      intracerebroventricular 6-hydroxydopamine and 5,7-dihydroxytryptamine selectively
      decreased [125I]RTI-55 binding to DA and 5-HT transporters, respectively, thereby
      confirming the selectivity of the assay conditions. The ligand-selectivity
      pattern of the whole brain minus caudate 5-HT transporter correlated
      significantly with that of the caudate 5-HT transporter, although there were some
      striking differences for selected test agents. Additional experiments resolved
      [125I]RTI-55 binding to the 5-HT transporter into two components. A ligand
      selectivity analysis of the two components failed to identify a highly selective
      test agent. In summary, the major findings of the present study are that
      [125I]RTI-55 labels both DA and 5-HT transporters in membranes prepared from
      whole brain minus caudate, that 50 nM paroxetine and either 1000 nM LR1111 or 500
      nM RTI-120 can be used as a blocking agent to generate selective assay conditions
      for the DA and 5-HT transporters, respectively, and that [125I]RTI-55 binding to
      the 5-HT transporter can be resolved into two similar components.

PMID- 7714770
TI  - Coadministration of cholinesterase inhibitors and idazoxan: effects of
      neurotransmitters in rat cortex in vivo.
AB  - Based on previous results indicating that cholinesterase inhibitors (ChEI) elicit
      a significant and simultaneous increase in acetylcholine (ACh) and norepinephrine
      (NE) levels, we studied whether the NE elevation could down-regulate ACh levels
      and possibly decrease the therapeutical effect of these drugs. A modified
      microdialysis technique without ChEI in the probe was used to study the putative
      interaction of these neurotransmitters in cerebral cortex of freely moving rats.
      We administered physostigmine (PHY) (0.03 mg/kg) and heptylphysostigmine (HEP) (2
      mg/kg) subcutaneously to animals pretreated with idazoxan (IDA) (i.p. or in the
      probe), a selective alpha-2 antagonist. IDA (20 mg/kg i.p. and 10(-4) M in the
      probe) did not modify the basal release of ACh. On the other hand, NE and
      dopamine (DA) were increased after both types of administration. PHY administered
      to rats pretreated with IDA (systemically or locally) induced a similar increase
      in the ACh levels as demonstrated for PHY alone. Conversely, coadministration of
      HEP with IDA i.p. produced a more sustained effect on ACh cortical levels than
      did HEP alone. These data suggest that a combination of cholinergic-adrenergic
      drugs may improve the pharmacological effect of ChEI.

PMID- 7714772
TI  - Differential blockade of voltage-sensitive calcium channels at the mouse
      neuromuscular junction by novel omega-conopeptides and omega-agatoxin-IVA.
AB  - This investigation assessed the ability of a variety of calcium channel blocking
      peptides to block synaptic transmission in the isolated mouse phrenic nerve
      hemidiaphragm. The synthetic version of the naturally occurring N-type voltage
      sensitive calcium channel (VSCC) blocker omega-conopeptide MVIIA (SNX-111) had no
      effect on nerve-evoked muscle contractions. The non-N-, non-L-type VSCC blocker,
      omega-conopeptide MVIIC (SNX-230), blocked neuromuscular transmission completely,
      as did the selective P-type VSCC blocker, omega-Aga-IVA. Subsequent evaluation of
      other synthetic omega-conopeptides and analogs disclosed a significant positive
      correlation between the test compounds' affinities for high-affinity SNX-230
      brain binding sites and their neuromuscular blocking potencies. Quantal analysis
      of transmitter release showed that SNX-230 abolished evoked endplate potentials
      completely, but had little effect on the amplitude and frequency of spontaneous
      miniature endplate potentials. Perineural focal recordings of presynaptic
      currents showed that SNX-230 did not block the neuronal action potential. These
      and other findings indicated that SNX-230 prevents transmitter release at the
      mouse neuromuscular junction by blocking calcium channels at presynaptic nerve
      endings. These calcium channels correspond pharmacologically to VSCCs associated
      with high-affinity binding sites in rat brain and are most probably either of the
      P- or Q-type.

PMID- 7714771
TI  - Modulation of basal and stress-induced release of acetylcholine and dopamine in
      rat brain by abecarnil and imidazenil, two anxioselective gamma-aminobutyric
      acidA receptor modulators.
AB  - The effects of imidazenil (6-(2-bromophenyl)-8-fluoro-4-H-imidazo[1-5-a][1
      4]benzodiazepine-3- carboxamide) and abecarnil (isopropyl-6-benzyloxy-4
      methoxymethyl-beta-carboline-3-carboxylate), new partial and selective
      benzodiazepine recognition site agonists, respectively, on basal and stress
      induced hippocampal acetylcholine and cortical dopamine release were determined
      with the microdialysis technique in freely moving rats. The actions of these new
      anxioselective and anticonvulsant drugs were compared with those of diazepam and
      midazolam, two classical benzodiazepine full agonists. Abecarnil (0.05-1 mg/kg
      i.p.), imidazenil (0.05-1 mg/kg i.p.), diazepam (2.5-10 mg/kg i.p.) and midazolam
      (2.5-10 mg/kg i.p.) inhibited basal hippocampal acetylcholine release in a dose
      dependent manner. In contrast, whereas diazepam and midazolam significantly
      decreased dopamine release in the prefrontal cortex, abecarnil and imidazenil had
      no effect on basal dopamine output. The effects of these drugs on both
      acetylcholine and dopamine release were antagonized by the benzodiazepine
      receptor antagonist flumazenil (1 mg/kg i.p.). Foot-shock stress (0.2 mA for 500
      msec/sec) delivered for 8 min induced a rapid and marked (+75%) increase in
      hippocampal acetylcholine output that persisted for approximately 40 min. Foot
      shock stress also increased dopamine release in the cerebral cortex; the effect
      was maximal (+90%) after 20 min and persisted for approximately 30 min. Prior
      administration of abecarnil or imidazenil at a dose (0.05 mg/kg) that did not
      significantly affect the basal release of either acetylcholine or dopamine
      completely prevented the effect of stress on the output of these
      neurotransmitters, an effect mimicked by higher doses of diazepam (2.5 mg/kg) and
      midazolam (2.5 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714773
TI  - Hydroxocobalamin (vitamin B12a) prevents and reverses endotoxin-induced
      hypotension and mortality in rodents: role of nitric oxide.
AB  - The cobalt atom of hydroxocobalamin (OHC) binds cyanide and nitric oxide (NO) and
      OHC attenuates vascular responses to NO in vitro. NO mediates the hypotension of
      endotoxemia. Thus, we tested the postulate that OHC may attenuate the acute phase
      hypotension and toxicity associated with administration of Escherichia coli
      endotoxin (LPS). Rats were given OHC (20 mg/kg i.v.) or phosphate-buffered saline
      (PBS, 1 ml/kg i.v.) 30 min before or 15 min after giving LPS (0.8 mg/kg i.v.).
      Administration of OHC to PBS-treated control rats did not affect mean arterial
      pressure (MAP), heart rate or the plasma or urine content of the reactive
      nitrogen intermediates nitrate and nitrite (RNI). LPS decreased MAP by 50 mm Hg
      in PBS-treated rats and increased the plasma and urinary content of RNI.
      Administration of OHC to PBS-treated rats did not affect MAP or RNI. However,
      treatment with OHC before or after giving LPS attenuated LPS-induced hypotension
      and increases in plasma RNI and enhanced LPS-induced urinary excretion of RNI.
      OHC (20 mg/kg i.p.) or cyanocobalamin (10 mg/kg i.p.) given to Swiss-Webster mice
      30 min before giving LPS (16 mg/kg i.p.) decreased the 24-hr mortality of LPS
      from 80 to 50% and the 36- and 96-hr mortality from 100 to 60% (OHC) or 70%
      (cyanocobalamin). Urine obtained from conscious rats given LPS (5 mg/kg i.p.) and
      OHC (20 mg/kg i.p.) exhibited a UV-visible absorbance spectrum with absorbance
      peaks characteristic of that formed after coincubation of NO and OHC.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7714774
TI  - Functional expression of transporter for beta-lactam antibiotics and dipeptides
      in Xenopus laevis oocytes injected with messenger RNA from human, rat and rabbit
      small intestines.
AB  - A heterologous gene expression system, Xenopus laevis oocytes, was used to prove
      the intestinal absorption of various beta-lactam antibiotics mediated by an H(+)
      dipeptide cotransport system in rat, rabbit and human small intestines. The
      microinjection of mRNA (messenger RNA) from rat intestine into Xenopus laevis
      oocytes led to significantly higher uptakes of p.o. active cephalosporins
      including zwitter-ionic derivatives (cephalexin, cephradine and cefadroxil) and
      dianionic derivatives (cefixime and ceftibuten) in comparison with oocytes
      injected with water, whereas the uptake of cefazolin, a parenterally administered
      derivative, was negligible in both mRNA- and water-injected oocytes. The uptake
      of cefadroxil was reduced significantly in the presence of dipeptide and various
      beta-lactam antibiotics, but not in the presence of an amino acid. After sucrose
      density gradient centrifugation of mRNA, the highest expression of transport
      activities of both cefadroxil and ceftibuten was observed in the same mRNA
      fraction with a size of 2.20 to 3.75 kilobases. mRNA-injected oocytes showed a
      marked pH-dependency in the uptakes of cefadroxil and ceftibuten, whereas water
      injected oocytes exhibited only modes uptakes. The most stimulated uptakes of
      cefadroxil and ceftibuten were observed at an external pH of 5.5 and 5.0,
      respectively. Furthermore, injection of mRNA isolated from either rat rabbit or
      human small intestine into oocytes produced significantly higher uptake of
      cefadroxil and ceftibuten compared with those by oocytes injected with water.
      Thus, intestinal absorption of p.o. active beta-lactam antibiotics was confirmed
      to be mediated by an H+ gradient-dependent transport system across the brush
      border membrane of rats, rabbits and humans. The carrier-protein for this process
      is likely a dipeptide transport system.

PMID- 7714775
TI  - Oral administration of clotrimazole and blockade of human erythrocyte Ca(++)
      activated K+ channel: the imidazole ring is not required for inhibitory activity.
AB  - The Ca(++)-activated K+ (Gardos) channel of erythrocytes plays a crucial role in
      K+ loss and dehydration of sickle erythrocytes; a potential therapeutic strategy
      would be to prevent dehydration by specifically blocking this channel. The
      authors report here on the activity of the clotrimazole (CLT) metabolite, 2
      chlorophenyl-bis-phenyl-methanol, which accounts for a portion of the blockade of
      the erythrocyte Gardos channel when CLT is given orally to normal volunteers.
      Administration of a single oral dose of 1 g of CLT to four normal healthy
      volunteers (approximately 15 mg/kg of body weight) resulted in 51% to 92% peak
      inhibition of the Gardos channel measured in whole blood 2 to 4 hr later.
      Inhibition remained detectable for 24 to 34 hr. Inhibition of the Gardos channel
      correlated best with the summed levels of CLT plus its two major metabolites (P <
      .002; apparent IC50 = 0.65 +/- 0.19 microM). In vitro experiments with 2
      chlorophenyl-bis-phenyl-methanol revealed dose-dependent inhibition of K
      transport and displacement of specifically bound 125I-charybdotoxin. Thus, the
      imidazole ring of CLT, which is required for antimycotic activity and associated
      with most of the historically observed toxicity, is not necessary for inhibition
      of the Gardos channel.

PMID- 7714776
TI  - Identification of the primary muscarinic autoreceptor subtype in rat striatum as
      m2 through a correlation of in vivo microdialysis and in vitro receptor binding
      data.
AB  - Muscarinic autoreceptors located on cholinergic nerve terminals are involved in
      the inhibitory feedback regulation of acetylcholine (ACh) release. Establishing
      the subtype identity of such sites provides a more complete understanding of both
      normal receptor function and the functional significance of receptor changes
      associated with various neurodegenerative diseases. In this study, a novel
      approach was used to identify the muscarinic autoreceptor in rat striatum. It
      involved the correlation of data from two different sources--in vivo
      microdialysis and in vitro receptor binding. Four standard muscarinic antagonists
      with varying binding profiles (scopolamine, pirenzepine, AF-DX116 and himbacine)
      were infused directly through a microdialysis probe into the striatum of
      conscious, freely moving rats. The objectives were to find the minimal
      concentration of each antagonist capable of manifesting a functional autoreceptor
      response (i.e., increased ACh release) and to compare the relative ability of the
      antagonists to bring about this effect with their relative abilities to bind to
      each of the cloned muscarinic receptor subtypes. The conclusion is that the
      muscarinic receptor mediating ACh release in rat striatum exhibits a
      pharmacological profile clearly consistent with it being of the m2 subtype.

PMID- 7714777
TI  - Effects and interactions of gentamicin, polyaspartic acid and diuretics on urine
      calcium concentration.
AB  - Gentamicin causes isolated, reversible calciuria in rats by an unknown mechanism.
      We hypothesized that gentamicin calciuria is related to nonantibacterial
      properties that may interfere with transtubular calcium transport (calcium
      channel blockade, Na,K-ATPase inhibition or competition with calcium for binding
      to the brush-border membrane). The calciuric effect of gentamicin was compared to
      the calcium channel blockers lanthanum and cobalt, the Na,K-ATPase inhibitor
      ouabain and the polycation aprotinin (which competes with gentamicin for brush
      border membrane binding). Although gentamicin 0.02 mmol/kg caused a 6-8-fold
      increase in urine calcium concentration, none of the other agents was calciuric.
      We also found that the calciuric effects of gentamicin and furosemide were
      additive, whereas the noncalciuric diuretic chlorothiazide had no effect on
      gentamicin calciuria. We also determined the effect of poly-L-aspartic acid
      (PAA), which binds gentamicin and prevents nephrotoxicity. PAA caused isolated
      calciuria similar in magnitude and character to gentamicin. However, PAA
      pretreatment decreased the magnitude of gentamicin calciuria to insignificance.
      PAA pretreatment did not prevent furosemide calciuresis. These results indicate
      that: 1) gentamicin and furosemide calciuria are caused by different mechanisms;
      2) gentamicin calciuria is probably not mediated by calcium channel blockade,
      Na,K-ATPase inhibition or displacement of brush-border membrane-bound calcium; 3)
      gentamicin and PAA calciuria may reflect interference with intracellular events
      related to transtubular calcium transport.

PMID- 7714778
TI  - Radioligand binding analysis of receptor subtypes in two FP receptor preparations
      that exhibit different functional rank orders of potency in response to
      prostaglandins.
AB  - The rat colon and Swiss 3T3 cells have been proposed as FP receptor preparations.
      However, the rank orders of potency for contraction of the rat colon and Ca++
      signaling in Swiss 3T3 cells were found to be disparate. Although both appeared
      to be FP receptor preparations in that PGF2 alpha and FP receptor selective
      analogs were the most potent agonists, the potency ranking for other PGs and
      their analogs differed markedly. This presented two alternative major hypotheses
      for interpreting these data: (1) Swiss 3T3 cells and the rat colon possess
      different FP receptor subtypes and (2) the rat colon contains a heterogeneous
      population of prostanoid receptors. To further characterize prostanoid receptor
      populations in these two preparations, radioligand binding studies were performed
      with 3H-PGE2 and 3H-17-phenyl-PGF2 alpha. The rank order of potency for
      inhibition of 3H-PGE2 binding in the rat colon was consistent with EP3 receptor
      pharmacology. Thus, MB 28767, sulprostone and PGE2 were potent inhibitors,
      whereas PGF2 alpha, PGD2 and other analogs were substantially less potent. The
      rank order of potency for inhibition of 3H-17-phenyl-PGF2 alpha binding in the
      rat colon was consistent with the presence of an FP receptor. Thus, the potency
      rank order for the natural PGs was PGF2 alpha > PGD2 > PGE2 and among the
      synthetic analogs only PGF2 alpha analogs were potent competitors. In Swiss 3T3
      cells an identical rank order of potency for eliciting a Ca++ transient signal
      and inhibition of 3H-17-phenyl-PGF2 alpha binding was obtained.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7714779
TI  - Dynorphin A modulates acute and chronic opioid effects.
AB  - A single dose of dynorphin A-(1-13) [dyn A(1-13)] is effective in suppressing the
      expression of opioid withdrawal and tolerance in morphine-dependent mice. In
      addition, this modulatory activity is retained by the corresponding non-opioid
      [des-Tyr1]-dynorphin A peptide [dynA(2-17)]. We have further investigated the non
      opioid nature of this activity by comparing the efficacies of dyn A(1-13) and (2
      17) under different experimental protocols with a variety of dosing regimens. The
      effect of dyn A(1-13) on withdrawal and tolerance expression was dose-dependent
      and could be enhanced by repeated dosing. Thus, the ED50 of naloxone to
      precipitate withdrawal jumping was increased 1.8-fold when morphine-dependent
      mice were treated with 4.2 mumol/kg dyn A(1-13) on the fourth day after pellet
      implantation and 2.4-fold on the sixth day with continued daily dyn A(1-13)
      treatment. The maximal effect was observed on day 6 when the ED50 of mice treated
      with 8.4 mumol/kg of dyn A(1-13) was increased nearly 6-fold over that of saline
      controls. Dyn A(2-17) proved to be nearly as effective as dyn A(1-13).

PMID- 7714780
TI  - The effect of verapamil on the transport of peptides across the blood-brain
      barrier in rats: kinetic evidence for an apically polarized efflux mechanism.
AB  - When the blood-brain barrier (BBB) transport of a series of model peptides that
      varied in their physicochemical properties (lipophilicity, size and hydrogen
      bonding potential) was determined using an in situ rat brain perfusion technique,
      an unexpected increase in flux with increasing peptide concentration was observed
      with one of the peptides. Further, inclusion of verapamil in the perfusion medium
      also increased permeability of the peptides. These observations were consistent
      with the presence of a polarized efflux system in the BBB that was saturable,
      could be competitively inhibited and showed substrate specificity. Such
      properties are similar to those of P-glycoprotein (P-gp), an apically localized
      efflux pump that has recently been reported to be present in the endothelial
      cells that constitute the BBB, and suggest that P-gp may be responsible for this
      activity. By measuring the BBB transport of the model peptides in the presence of
      verapamil (a P-gp inhibitor), the intrinsic BBB permeabilities (due to passive
      diffusion only) were obtained. The presence of verapamil caused a significant
      increase in the BBB permeabilities of six of the seven model peptides. When the
      intrinsic permeability coefficients were correlated with several physicochemical
      parameters, it was shown that hydrogen bonding potential rather than
      lipophilicity had the greatest influence on the passive diffusion of these model
      peptides across the BBB. From these studies it can be concluded that inhibition
      of P-gp, as well as reduction of the hydrogen bonding potential, can be used as
      strategies to increase peptide transport across the BBB.

PMID- 7714781
TI  - Melatonin agonists modulate 5-HT2A receptor-mediated neurotransmission:
      behavioral and biochemical studies in the rat.
AB  - Interactions between melatonin and serotonin type 2A (5-HT2A) receptors in the
      regulation of the sleep-wakefulness cycle in the rat have been reported. We
      studied the acute effects of melatonin and related agonists on 5-HT2A
      neurotransmission as reflected in behavioral (head shake) and biochemical
      [phosphoinositide (PI) hydrolysis] responses to 5-HT2A receptor stimulation. Like
      5-HT1A agonists and antidepressants, acute administration of melatonin and
      related agonists inhibited the 5-HT2A-mediated (+/-)-1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropane-induced head shake in a dose-dependent manner.
      Consistent with these behavioral findings, in vitro incubation of cortical slices
      with melatonin agonists robustly inhibited 5-HT2A receptor-mediated PI hydrolysis
      in a noncompetitive manner. 2-Iodomelatonin-induced reductions in 5-HT2A
      stimulated PI hydrolysis were blocked by preincubation with the melatonin
      antagonist N-acetyltryptamine. Further, pretreatment of rats in vivo with
      melatonin and related agonists reduced the cortical PI hydrolysis response to the
      5-HT2A agonist alpha methyl-5-HT but did not alter cortical 5-HT2A receptor
      density. The present data support an interaction between melatonin and 5-HT2A
      receptors in the central nervous system.

PMID- 7714782
TI  - Combination treatment of the partial D2 agonist terguride with the D1 agonist SKF
      82958 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian
      cynomolgus monkeys.
AB  - The optimal combination of a dopamine D2 agonist and a D1 agonist was evaluated
      for symptomatic treatment of Parkinson's disease. Behavioral effects of
      combination treatment of the full D2 agonist quinpirole or the partial D2 agonist
      terguride with the full D1 agonist SKF 82958 [(I) 6-Chloro-7, 8-dihydroxy-3-allyl
      1-phenyl-2, 3, 4, 5-tetra-hydro-1H-3-benzazepine] were investigated in 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys
      with attention to the induction of hyperactivity such as irritability,
      excitability and aggressiveness and of dyskinesias such as licking of paws,
      chewing and biting. Both quinpirole and SKF 82958 alone improved the parkinsonism
      with a slight induction of the hyperactivity and dyskinesias. Terguride also
      improved the parkinsonism but did not induce the hyperactivity and dyskinesias.
      Combination treatment of quinpirole with SKF 82958 not only showed a tendency to
      augment the antiparkinsonian effects but also induced the marked hyperactivity
      and dyskinesias. On the other hand, combination treatment of terguride with SKF
      82958 also augmented the antiparkinsonian effects but did not induce any
      hyperactivity and dyskinesias. These findings suggest that combination therapy
      with a partial D2 agonist and a full D1 agonist or monotherapy with a dopamine
      agonist that has both partial D2 and full D1 agonist properties might be
      beneficial for treating motor dysfunction in Parkinson's disease without inducing
      dopaminergic side effects.

PMID- 7714783
TI  - Tetrandrine, a Ca++ antagonist: effects and mechanisms of action in vascular
      smooth muscle cells.
AB  - Tetrandrine, an alkaloid extracted from the Chinese medicinal herb Radix
      stephania tetrandrae, has traditionally been used to treat hypertension. In the
      present study, the effect of tetrandrine on vascular smooth muscle was
      investigated by using the rat tail artery as a model of a resistance vessel.
      Tetrandrine relaxes the tension in tail artery helical strips produced by
      depolarization with 60 mM KCl. Further studies show that tetrandrine inhibits the
      KCl-induced intracellular Ca++ increase and L-type voltage-dependent Ca++ channel
      currents, suggesting that tetrandrine relaxes the vessel via inhibition of Ca++
      influx through Ca++ channels. Tetrandrine also inhibits norepinephrine (NE)
      induced vasocontraction in the presence of extracellular Ca++. It does not,
      however, inhibit NE-induced vasocontraction in the absence of extracellular Ca++.
      Tetrandrine also inhibits the NE-induced intracellular Ca++ increase in the
      presence of extracellular Ca++ and has no effect on the NE-induced intracellular
      Ca++ increase in the absence of extracellular Ca++. This suggests that
      tetrandrine also blocks NE-induced Ca++ influx but not NE-induced Ca++ release
      from the intracellular Ca++ stores. Furthermore, tetrandrine inhibits
      thapsigargin-induced intracellular Ca++ concentration increase, suggesting that,
      in addition to blocking Ca++ influx, tetrandrine also may interfere with the
      interaction between thapsigargin and Ca++ adenosine triphosphatase.

PMID- 7714784
TI  - Adenosine receptor activation modulates intraocular pressure in rabbits.
AB  - The relatively selective adenosine A1 agonists N6-cyclohexy-ladenosine (CHA), R(
      )-N6-(2-phenylisopropyl)adenosine (R-PIA) and S(+)-N6-(2
      phenylisopropyl)adenosine (S-PIA); the A2a agonist 2-p-carboxyethyl)phenethyl
      amino-5'-N-ethylcarbox-amidoadenosin e (CGS-21680) and the nonselective A2
      agonist 2-phenylaminoadenosine (CV-1808) were evaluated in vivo for their effects
      on aqueous humor dynamics and in vitro for their action on 3H-norepinephrine
      release and cAMP accumulation in the isolated iris/ciliary body. These studies
      demonstrated that adenosine agonists can modulate intraocular pressure (IOP).
      Except for CV-1808, the topical administration of adenosine agonists produced a
      unilateral dose-related reduction in IOP with a potency order of R-PIA = CHA >
      CGS-21680 > S-PIA > CV-1808. Although CV-1808 did not lower IOP, it did induce a
      significant dose-dependent rise in IOP. Neither the reduction in IOP induced by R
      PIA nor the rise in IOP induced by CV-1808 was affected by surgical removal of
      the superior cervical ganglion. However, the adenosine agonist-induced reduction
      in IOP was associated with a significant decrease in aqueous flow. In vitro
      studies demonstrated that the adenosine agonists did not alter the evoked release
      of 3H-norepinephrine; however, they were effective in suppressing the
      accumulation of cAMP, and this response was blocked by pretreatment with the
      antagonist 8-cyclopentyl-1,3-dimethylxanthine. These studies provide evidence
      that adenosine agonists lower IOP by activating postjunctional adenosine A1
      receptors. This response is associated with a reduction in aqueous flow and the
      modulation of cAMP in the iris/ciliary body.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714785
TI  - Behavioral and neurochemical effects of opioids in the paramedian midbrain
      tegmentum including the median raphe nucleus and ventral tegmental area.
AB  - Injections of morphine into the median raphe nucleus (MR) of rats produced a dose
      dependent, naloxone sensitive increase in locomotor activity. Dose-dependent
      increases in activity also could be produced by intra-MR injections of the mu
      opioid agonist Tyr-D-Ala-Gly-MePhe-Gly(ol)-enkephalin (DAMGO) and the delta
      opioid agonist D-Pen2,D-Pen5-enkephalin (DPDPE), but not by the kappa-opioid
      agonist Dynorphin A (1-13). Mapping studies demonstrated that DPDPE produced
      larger responses when injected into the MR than into a number of adjacent
      structures, whereas the effective zone for obtaining responses with DAMGO
      appeared to extend forward into the caudal portion of the ventral tegmental area.
      The induction of hyperactivity by DPDPE and DAMGO was unaltered in animals with
      large depletions of forebrain serotonin produced by injections of 5,7
      dihydroxytryptamine, suggesting that these effects were not mediated through
      serotonergic mechanisms. Post-mortem assays indicated that serotonin turnover in
      the hippocampus was reduced slightly after intra-MR injections of DPDPE, but no
      effects were observed after injections of DAMGO or Dynorphin A (1-13). Injections
      of either DPDPE or DAMGO into the MR resulted in a large increase in dopamine
      turnover in the nucleus accumbens. Finally, intra-MR injections of DAMGO or
      Dynorphin A(1-13), but not DPDPE, stimulated ingestive behavior in nondeprived
      animals, although the effects were substantially smaller than those seen after
      injections of muscimol. These results demonstrate that pronounced behavioral and
      neurochemical effects can be produced by stimulation of opioid receptors within
      the MR and that the pattern of these effects depends upon which opioid receptor
      subtype is stimulated.

PMID- 7714786
TI  - Regulation of jejunal arterioles by capsaicin-sensitive nerves in Nippostrongylus
      brasiliensis-sensitized rats.
AB  - The mechanisms by which sensory nerves elicit dilation of serosal arterioles in
      the jejunum of rats sensitized to the nematode Nippostrongylus brasiliensis were
      studied using intravital microscopy. Capsaicin (0.002-2 micrograms), applied as a
      bolus topically to the serosa, produced a substantially larger dilation in the
      sensitized rats than in unsensitized rats. Abolition of the primary afferent
      nerves by neonatal treatment with capsaicin and blockade of capsaicin with the
      antagonist ruthenium red reduced markedly the dilator actions of capsaicin. Mast
      cell products are important in the actions of capsaicin, because pretreatment
      with dexamethasone (4 mg/kg), to eliminate mast cells by a macrophage-dependent
      mechanism, abrogated the actions of capsaicin. In addition, superfusion of the H1
      receptor antagonist diphenhydramine (2 microM) blocked the actions of capsaicin.
      Neither cyclooxygenase products nor platelet-activating factor was involved in
      capsaicin-induced dilation. The actions of capsaicin and histamine were mediated
      via a nitric oxide (NO)-dependent mechanism, because superfusion of an inhibitor
      of NO synthase (NG-nitro L-arginine methyl ester, 10 microM) blocked their
      effects. This inhibition of capsaicin-elicited dilation by NG-nitro L-arginine
      methyl ester was prevented by L-arginine (100 microM), the substrate for NO
      synthase. Thus the arteriolar dilation evoked by capsaicin activation of primary
      afferent nerves in N. brasiliensis-sensitized rats involves predominantly the
      release from mast cells of histamine, which then dilates the vessels by a NO
      dependent mechanism.

PMID- 7714787
TI  - Bradykinin acting on B2 receptors contracts colon circular muscle cells by IP3
      generation and adenylate cyclase inhibition.
AB  - Receptor subtypes and intracellular signaling events involved in bradykinin
      evoked contraction of colonic circular muscle are unknown. We studied the roles
      of inositol trisphosphate (IP3) and cyclic AMP generation and the selectivity for
      B1 and B2 receptors in guinea pig colon. Bradykinin induced concentration
      dependent contraction of circular muscle strips with an EC50 of 2 x 10(-8) M that
      was inhibited by the B2 antagonist D-Argo-(Hyp3,Thi5,8,D-Phe7)-bradykinin but not
      the B1 antagonist des-Arg9-[Leu8]bradykinin. The B1 agonist des-Arg9-bradykinin
      did not evoke contraction or relaxation. Bradykinin induced concentration
      dependent shortening of isolated myocytes from circular muscle with an EC50 of 2
      x 10(-11) M that was inhibited by the B2 but not the B1 antagonist, confirming
      the myogenic nature of the bradykinin receptors. Persistence of myocyte
      contraction in a calcium-free medium with EGTA confirmed the lack of dependence
      on extracellular calcium. In colon muscle tissue, bradykinin evoked concentration
      dependent IP3 generation with an EC50 of 10(-7) M and a maximal level of 58 +/-
      17 pmol/mg of protein at 10(-4) M that was inhibited by the B2 but not the B1
      antagonist. Bradykinin, acting on B2 receptors, inhibited cyclic AMP formation
      after forskolin (10(-5) M) with an EC50 of 3 x 10(-8) M and maximal inhibition of
      48% at 10(-5) M. In conclusion, bradykinin induces colon muscle contraction via
      myogenic non-B1 receptors, which are likely of the B2 subtype, with
      phosphoinositide turnover activation and adenylate cyclase inhibition.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7714788
TI  - Intravenous caffeine in stimulant drug abusers: subjective reports and
      physiological effects.
AB  - The present study was conducted to examine the self-reported (i.e., subjective)
      and physiological effects of intravenous caffeine in 10 subjects with histories
      of stimulant drug abuse. Under double-blind conditions, subjects received each
      dose of caffeine (0, 37.5, 75, 150 or 300 mg/70 kg) twice according to a latin
      square design; injections were 10 sec in duration and separated by at least 24
      hr. Effects were measured before injection and repeatedly afterward for 60 min.
      Caffeine dose-dependently increased ratings of positive mood (e.g., increased
      ratings of drug liking and high), which peaked at 2 min after injection and
      progressively decreased. Caffeine also dose-dependently increased the frequency
      of stimulant identifications on the Pharmacological Class Identification
      Questionnaire (e.g., like cocaine, amphetamine). Caffeine also produced negative
      mood effects (e.g., increased ratings of bad effects) and increases in self
      reported desire for cocaine. In contrast to the positive-mood effects, the
      negative-mood effects were of smaller magnitude and only significant at the
      highest dose. Caffeine increased reports of unusual smells and tastes. Caffeine
      decreased heart rate (7 bpm) and skin temperature (4 degrees C), and increased
      systolic and diastolic blood pressures (8 and 6 mm Hg, respectively). The mood
      effects but not the physiological effects of intravenous caffeine were similar to
      those previously observed with cocaine in studies using similar methods and
      subjects. Intravenous caffeine administration may provide a useful model system
      for investigating factors relevant to the use and abuse of stimulant drugs.

PMID- 7714789
TI  - SNC 80, a selective, nonpeptidic and systemically active opioid delta agonist.
AB  - The present study has investigated the pharmacology of SNC 80, a nonpeptidic
      ligand proposed to be a selective delta agonist in vitro and in vivo. SNC 80 was
      potent in producing inhibition of electrically induced contractions of mouse vas
      deferens, but not in inhibiting contractions of the guinea pig isolated ileum
      (IC50 values of 2.73 nM and 5457 nM, respectively). The delta selective
      antagonist ICI 174,864 (1 microM) and the mu selective antagonist CTAP (1 microM)
      produced 236- and 1.9-fold increases, respectively, in the SNC 80 IC50 value in
      the mouse vas deferens. SNC 80 preferentially competed against sites labeled by
      [3H]naltrindole (delta receptors) rather than against those labeled by [3H]DAMGO
      (mu receptors) or [3H]U69, 593 kappa receptors) in mouse whole-brain assays. The
      ratios of the calculated Ki values for SNC 80 at mu/delta and kappa/delta sites
      were 495- and 248-fold, respectively, which indicates a significant degree of
      delta selectivity for this compound in radioligand binding assays. SNC 80
      produced dose- and time-related antinociception in the mouse warm-water tail
      flick test after i.c.v., i.th. and i.p. administration. The calculated A50 values
      (and 95% C.I.) for SNC 80 administered i.c.v., i.th. and i.p. were 104.9 (63.7
      172.7) nmol, 69 (51.8-92.1) nmol and 57 (44.5-73.1) mg/kg, respectively. The
      i.c.v. administration of SNC 80 also produced dose- and time-related
      antinociception in the hot-plate test, with a calculated A50 value (and 95% C.I.)
      of 91.9 (60.3-140.0) nmol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714790
TI  - Structural determinants of the melanocortin peptides required for activation of
      melanocortin-3 and melanocortin-4 receptors.
AB  - The melanocortins are peptide products of proopiomelanocortin post-translational
      processing that, among other functions, are thought to influence cognition.
      Recently, we isolated genes encoding two human melanocortin receptors, the
      melanocortin-3 receptor (hMC3R) and the melanocortin-4 receptor (hMC4R), which
      are expressed primarily in brain. We undertook the present studies to examine the
      structural features of melanocortins that determine activation of these two
      receptors. For our studies we expressed the coding regions of the hMC3R and hMC4R
      genes in Hepa cells using the eukaryotic expression vector CMVneo and examined
      the generation of intracellular cyclic 3',5'-adenosine monophosphate in response
      to stimulation with various melanocortins. Our findings indicate that the core
      heptapeptide sequence common to most of the melanocortins (amino acids 4-10 of
      adrenocorticotropic hormone [ACTH]) is the primary determinant for activation of
      hMC3R but, in addition, tyrosine2 is necessary for maximal response. Activity of
      hMC4R is heavily dependent on proline12, but full activity also requires a
      contribution by tyrosine2. These findings may provide insight into the
      development of targeted ligands for the brain melanocortin receptors.

PMID- 7714791
TI  - Low endogenous dopamine function in brain predisposes to high alcohol preference
      and consumption: reversal by increasing synaptic dopamine.
AB  - Using inbred strains of mice that differ widely in their innate preference for
      and consumption of ethanol, we demonstrate, in ethanol-preferring C57BL/6J (C57)
      mice, decreased dopamine (DA) content and turnover in the terminals of the
      mesolimbic and mesostriatal dopamine neurons, compared with ethanol-avoiding
      DBA/2J and BALBc mice. These data suggest that genetically determined
      hypodopaminergic function in these pathways plays a role in the predisposition to
      high voluntary intake of ethanol. DA turnover in these areas was selectively
      increased by ethanol in C57 mice, which suggests that these DA neurons are among
      the central substrates of ethanol action in brain. In keeping with this
      hypothesis, augmenting synaptic DA concentrations by enhancing the synthesis by L
      3-4-dihydroxyphenylalanine with carbidopa, or by decreasing its degradation by
      monoamine oxidase-B blockade with selegiline, led to marked decreases in ethanol
      preference and in the high voluntary consumption of ethanol in C57 mice. The
      selegiline-mediated decrease in ethanol preference and drinking in C57 mice could
      be blocked selectively by D1 and D2 DA receptor antagonists, which suggests that
      DA activity at D1 and D2 receptors plays an important role in this behavior.
      Indeed, the high preference for ethanol in C57 animals could be attenuated by
      direct DA receptor activation by either D1 or D2 agonists.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7714792
TI  - Adrenergic modulation of a spinal sympathetic reflex in the rat.
AB  - Patients with spinal cord injury involving transection of the lower cervical or
      upper thoracic spinal cord can experience an autonomic hyperreflexia
      characterized by exaggerated blood pressure increases in response to visceral or
      somatic stimuli such as skin stimulation and urinary bladder or rectal
      distention. These cardiovascular responses are mediated by activation of spinal
      sympathetic reflex (SSR) circuits in the segments below the transection that are
      no longer controlled by their supraspinal inputs. We have examined the SSR in
      decerebrate, unanesthetized, paralyzed, artificially ventilated rats after acute
      spinal transection in the sixth cervical segment and have determined its
      sensitivity to i.v. administration of clonidine and other agents interacting with
      alpha-2 adrenergic receptors. The SSR amplitude, determined as the area of the
      averaged excitatory potential evoked on the splanchnic sympathetic nerve by
      single stimuli (300 microA) applied to the seventh thoracic dorsal root, was
      reduced to 14% +/- 6% of control with a cumulative dose of clonidine of 27
      micrograms/kg. This inhibition was completely reversed by rauwolscine, idazoxan
      and RX821002, but not by prazosin. Both guanabenz and UK-14304 also reduced the
      SSR amplitude (9% +/- 3% of control at 0.4 mg/kg and 11% +/- 6% of control at
      0.08 mg/kg, respectively). These results indicate that activation of alpha-2
      adrenergic receptors, within either the dorsal or intermediolateral horns of the
      spinal cord or within sympathetic ganglia, can significantly reduce transmission
      of information through SSR circuits after spinal cord injury.

PMID- 7714793
TI  - Adverse effects of paternal opiate exposure on offspring development and
      sensitivity to morphine-induced analgesia.
AB  - We have shown previously that chronic morphine administration to adolescent male
      rats produced a number of gender specific deficits in their offspring. The
      purpose of the present studies was to extend our earlier observations by
      examining the acute, direct effects of morphine exposure to male rats on their
      fertility and the development of viable offspring. Sexually mature male rats were
      injected with a single dose of morphine (25 mg/kg) and 24 hr later were bred with
      drug-naive females. Fertility rates (vaginal plugs and pregnancies) were
      monitored throughout the breeding period as was the development of the offspring.
      Our results showed that a large, acute dose of morphine given to drug-naive male
      rats 24 hr before the initiation of breeding had no effect on fertility rates,
      but produced several adverse effects on fetal outcome. Litter sizes in morphine
      derived offspring were considerably smaller than in controls and mortality rates
      were more than 6 times higher. Moreover, morphine-derived male, but not female,
      offspring had a significantly enhanced sensitivity to the antinociceptive effects
      of morphine. Collectively, these data suggest that acute paternal morphine
      exposure just before breeding with drug-naive females had no effect on fertility,
      but exerted negative effects on the viability and development of their offspring.
      These results represent the most compelling evidence to date that paternal opiate
      exposure can adversely affect fetal outcome and are particularly striking in that
      they were produced by a single injection of morphine. We are aware of no animal
      studies, clinical cases or anecdotal reports in humans in which such a phenomenon
      has been described.

PMID- 7714794
TI  - The effect of chemical substitution on the metabolic activation, metabolic
      detoxication, and pharmacological activity of amodiaquine in the mouse.
AB  - The adverse reactions associated with the antimalarial amodiaquine (AQ),
      agranulocytosis and hepatotoxicity, have been attributed to the bioactivation of
      the drug to a quinone imine metabolite. Therefore the effect of chemical
      modification on the metabolism of AQ was studied, with particular reference to
      the prevention of bioactivation and the introduction of glucuronidation.
      Glutathione conjugates of AQ and desethylAQ were eliminated in bile after
      intraportal administration of [3H]AQ (54 mumol/kg, 20 microCi/kg) to anesthetized
      male CD1 mice. Thioether conjugates excreted into bile over 3 h accounted for 28%
      of the administered dose. Fluorine substitution at the C-4 position of AQ blocked
      bioactivation, as measured by formation of thioether conjugates, and resulted in
      a 5-fold decrease in biliary excretion of radiolabeled dose: ca 6% versus ca 29%.
      Additional substitution of a primary alcohol function into one of the ethyl
      moieties introduced glucuronidation as a pathway of elimination, with 10% of the
      dose being excreted in bile as an O-glucuronide of the parent compound over a 3-h
      period; excretion of total radioactivity in bile increased 2.5-fold. These
      substitutions resulted in a 2-fold greater excretion of radiolabel into urine:
      41% and 39% for DFAQ and HDFAQ, respectively, versus 23% for AQ. Novel carboxylic
      acid and N-oxide metabolites of the fluorinated analogues were identified. AQ and
      the two fluorinated analogues had similar activity against Plasmodium berghei in
      mice. These results demonstrate that the metabolism of AQ can be diverted from
      extensive bioactivation to direct detoxication by simple chemical substitutions
      that do not impair pharmacological activity.

PMID- 7714795
TI  - Differential effects of dopamine D1 and D2 receptor agonists on schedule
      controlled behavior of squirrel monkeys.
AB  - The effects of dopamine agonists differing in affinity and selectivity at D1 and
      D2 types of dopamine receptors were compared in squirrel monkeys responding under
      two different schedules of reinforcement: a fixed-interval (FI) schedule of
      stimulus-shock termination and a fixed-ratio (FR) schedule of food presentation.
      Dopamine D1 family agonists included dihydrexidine, SKF 81297, SKF 82958, R-6-Br
      APB, SKF 83189, SKF 77434, SKF 75670 and R- and R, S-SKF 38393. Dopamine D2
      agonists included (+)-PHNO, quinpirole and N-0434; nonselective DA agonists
      included R(-)-apomorphine and CY 208-243. The behavioral effects of D1 agonists
      differed qualitatively from those of D2 and nonselective DA agonists. D1 agonists
      produced dose-related decreases in both FI and FR responding, with comparable
      doses being effective under the two schedules. The rank order of potency for the
      rate-decreasing effects of these drugs was R(+)-6-Br-APB > SKF 75670 > SKF 82958
      > R-SKF 38393 > SKF 81297 > SKF 77434 > SKF 83189 > dihydrexidine > R, S-SKF
      38393. In contrast, D2 and nonselective DA agonists produced significant
      increases in rates of FI responding at doses that reduced FR response rates. The
      rank order of potency for the rate-increasing effects of these drugs under the FI
      schedule was (+)-PHNO > N-0434 > R-apomorphine > CY 208-243 >
      quinpirole.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714796
TI  - Pharmacokinetic-pharmacodynamic modelling of the cardiovascular effects of R- and
      S-N6-phenylisopropyladenosine in conscious normotensive rats.
AB  - Recently, the commercially available adenosine receptor agonist S-N6
      phenylisopropyladenosine (S-PIA) has been demonstrated to be contaminated with
      the more potent R-diastereomer. The potency of S-PIA may therefore have been
      overestimated in previously published in vivo studies. Our objective was to
      determine the potency of both diastereomers in conscious normotensive rats by
      using an integrated pharmacokinetic-pharmacodynamic model. In a cross-over
      designed study, the animals received i.v. infusions of 177 micrograms/kg (0.51
      mumol/kg) R-N6-phenylisopropyladenosine (R-PIA) and 4000 micrograms/kg (11.6
      mumol/kg) S-PIA. The infusion of S-PIA corresponded to a simultaneous
      administration of 3823 micrograms/kg (11.1 mumol/kg) and 177 micrograms/kg (0.51
      mumol/kg) of the S- and R-diastereomer, respectively. During the experiment, time
      courses of heart rate and blood pressure were recorded continuously. Serial
      arterial blood samples were collected and concentrations were determined by using
      a stereoselective high-performance liquid chromatography assay. After
      administration of R-PIA, the individual concentration-effect relationships could
      be quantified by the sigmoidal Emax model, yielding an EC50 value of 24 +/- 3
      ng/ml for the reduction in heart rate (mean +/- S.E., n = 12). After
      administration of S-PIA, a similar EC50 value was obtained when heart rate was
      correlated to concentrations of R-PIA. Modelling of the concentration-effect data
      according to a competitive interaction model did not yield pharmacodynamic
      parameter estimates for S-PIA. In conclusion, the cardiovascular effects observed
      after infusion of S-PIA may be attributed entirely to the presence of R-PIA.

PMID- 7714797
TI  - Role of presynaptic input in the ontogeny of adrenergic cell signaling in rat
      brain: beta receptors, adenylate cyclase and c-fos protooncogene expression.
AB  - Neurotransmitters act as trophic factors during brain development, regulating
      expression of genes that control cellular differentiation. One example of this
      trophism is the beta adrenergic signaling cascade: activation of beta receptors
      leads sequentially to increased cyclic AMP (cAMP), augmented expression of the
      nuclear transcription factor, c-fos, and induction of ornithine decarboxylase
      (ODC), an enzyme obligatory for neuronal development. After neonatal lesioning of
      noradrenergic nerves with 6-hydroxydopamine (6-OHDA), beta receptors become
      uncoupled from ODC induction in the cerebellum, a region that undergoes its peak
      of cell replication/differentiation postnatally. The present study investigates
      the mechanism for uncoupling of beta receptors from response elements. In the
      cerebellum, 6-OHDA had minor effects on beta receptor binding capabilities and
      caused slight supersensitivity of the beta adrenergic response of adenylate
      cyclase; the latter reflected increased expression of cyclase catalytic subunits,
      rather than a specific effect on beta receptor coupling. In contrast, the linkage
      of cAMP to cerebellar c-fos expression showed marked deficiencies in lesioned
      animals and a corresponding loss of the ability of beta receptors to induce c
      fos; accordingly, this is a likely point at which beta adrenergic control of ODC
      is programmed by neuronal input. A critical period exists for neurotrophic
      influence: the alterations persisted past the point at which cerebellar
      norepinephrine levels recovered, and comparable effects did not occur in earlier
      developing regions. In the forebrain, for example, neonatal lesions produced
      receptor upregulation and supersensitivity of c-fos to cAMP stimulation. These
      results suggest that presynaptic input is vital in programming beta adrenergic
      responsiveness during a critical period of development, and that interruption of
      transsynaptic events occurring at this time can lead to lasting alterations in
      neuronal differentiation and responsiveness.

PMID- 7714798
TI  - Pretranslational down regulation of cytochrome P450 2C11 in vitamin A-deficient
      male rat liver: prevention by dietary inclusion of retinoic acid.
AB  - Manipulation of vitamin A intake has been associated with altered rates of
      cytochrome P450 (P450)-mediated microsomal drug oxidation. Dietary vitamin A
      deficiency reportedly results in decreased rates of P450-dependent substrate
      oxidation, but the mechanisms underlying these changes remain unclear. In this
      study, the effects of dietary vitamin A modulation, as well as dietary inclusion
      of all-trans-retinoic acid (ATRA), on major constitutive P450s were defined.
      Total microsomal P450 in deficient male rats was decreased to 72% of control
      (0.63 +/- 0.07 vs. 0.88 +/- 0.08 nmol/mg of protein; P < .05); this was prevented
      by inclusion of ATRA (12 micrograms/g) in the deficient diet. Dietary vitamin A
      deficiency decreased rates of P450 2C11-mediated testosterone 2 alpha- and 16
      alpha-hydroxylation in rat liver to 44 and 47% of respective adequate control,
      whereas rates of 6 beta- and 7 alpha-hydroxylation of the steroid were unaltered;
      inclusion of ATRA into the deficient diet prevented the loss of 2C11 activities.
      Immunoblot and RNA analysis revealed decreases in P450 2C11 apoprotein and its
      corresponding mRNA in liver from deficient rats that was prevented by inclusion
      of ATRA in the deficient diet. Serum testosterone concentrations were reduced in
      deficient rats and this also was prevented by dietary ATRA. To discern whether
      this was a direct effect of vitamin A on P450 2C11 regulation, further
      experiments evaluated the effect of ATRA administration to male rats maintained
      on standard rat chow (vitamin A-adequate). Dose- and time-dependent decreases in
      P450 2C11 activity were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714799
TI  - [3H]WIN 35,428 binding in the caudate nucleus of the rabbit: evidence for a
      single site on the dopamine transporter.
AB  - The binding of the potent cocaine analog, WIN 35,428 ((-)-2-beta-carbomethoxy-3
      beta-(4-fluorophenyl)tropane 1,5-napthalenedisulfonate), was investigated in
      adult Dutch Belted rabbits by using membrane fractions prepared from fresh
      caudate nucleus. The consistent finding of this study was that [3H]WIN 35,428
      binds to a single class of sites. For example: 1) kinetic analysis revealed that
      the rate of association and dissociation of [3H]WIN 35,428 was linear; 2)
      analyses of saturation experiments or homotopic displacement with cold WIN 35,428
      by three separate methods statistically favored a one-site model; and 3)
      heterotropic displacement with drugs that bind to the dopamine (DA) transporter
      consistently yielded only a single class of binding sites as reflected by a
      complete displacement of [3H]WIN 35,428 and Hill slopes of approximately 1
      (range, 0.89-1.06). The rank order of potencies (Ki) obtained in the competition
      experiments was: mazindol > nomifensine > (-)-cocaine > bupropion > (-)
      norcocaine >> desipramine > DA > (+)-cocaine >> norepinephrine > citalopram > 5
      hydroxytryptamine. The affinities of these drugs at the [3H]WIN 35,428 binding
      site was significantly correlated (r = 0.96, P < .001) with their potencies for
      inhibiting the uptake of DA, but not the uptake of norepinephrine or 5
      hydroxytryptamine. Because [3H]WIN 35,428 binding was fully displaced by cocaine
      and the displacement was stereoselective, with (-)-cocaine being 200-fold more
      potent than (+)-cocaine, we conclude that [3H]WIN 35,428 was binding to a single
      cocaine site. Taken together, these findings indicate that [3H]WIN 35,428 binds
      to a single cocaine site on the DA transporter of the rabbit with a Kd of 3.2 +/-
      0.4 nM and a maximum binding of 0.39 +/- 0.04 pmol/mg of caudate tissue.

PMID- 7714801
TI  - High-dose vitamin E supplementation has no effect on ethanol-induced pathological
      liver injury.
AB  - The effect of alpha-tocopherol (alpha-T) supplementation on ethanol-induced liver
      damage was studied. The intragastric feeding rat model was used in this study.
      Both normal and alpha-T supplemented animals (3125 IU/kg body weight) were fed
      liquid diet and ethanol for 1 mo. In pair-fed animals, ethanol was isocalorically
      replaced by dextrose. The blood ethanol level in the ethanol-fed groups was
      between 150 to 350 mg/dl. Lipid peroxidation was assessed by measuring liver
      thiobarbituric acid reactive substances (TBARS) and conjugated dienes. Liver
      damage was assessed by light microscopy. Overall, chronic ethanol treatment
      resulted in increase in TBARS and conjugated dienes in both normal (60% and 35%,
      P < .01, respectively) and alpha-T-supplemented groups (50% and 47%, P < .01,
      respectively). In animals receiving either dextrose or ethanol and regular diet,
      there was a significant inverse correlation between liver alpha-T and TBARS (r =
      0.88, P < 0.01) and conjugated dienes (r = -0.75, P < .05). In contrast, in the
      vitamin E-supplemented rats, a significant positive correlation was observed
      between liver alpha-T, TBARS (r = 0.78, P < .01) and conjugated dienes (r = 0.87,
      P < .01). Of major significance is that alpha-T supplementation had no effect on
      ethanol-induced pathological changes in the liver. In conclusion, these results
      show that in the intragastric feeding model, alpha-T supplementation had no
      protective effect on ethanol-induced liver damage.

PMID- 7714800
TI  - Repeated administration of cocaine or amphetamine alters neuronal responses to
      glutamate in the mesoaccumbens dopamine system.
AB  - The development of behavioral sensitization during repeated administration of
      psychomotor stimulants is a well characterized phenomenon which involves
      alterations in dopaminergic neurotransmission within the mesoaccumbens system.
      However, recent evidence indicating that both behavioral sensitization and
      certain of its neuronal correlates can be prevented by excitatory amino acid
      receptor antagonists suggests an integral role for glutamate systems in
      sensitization processes. Therefore, we have determined whether repeated
      psychomotor stimulant administration can alter responsiveness of the
      mesoaccumbens dopamine (DA) system to glutamate. After five daily injections of
      either cocaine (15.0 mg/kg) or d-amphetamine (5.0 mg/kg), rats were subjected to
      in vivo single cell recording to determine the efficacy of iontophoretically
      administered glutamate in altering the firing of ventral tegmental area DA
      neurons and nucleus accumbens neurons. Current-response determinations indicated
      that the responsiveness of ventral tegmental area DA neurons to glutamate was
      significantly enhanced in d-amphetamine-treated and cocaine-treated rats in that
      the neurons entered a state of apparent depolarization block at significantly
      lower iontophoretic currents. In contrast, nucleus accumbens neurons in
      psychomotor stimulant-treated rats were significantly less sensitive to the rate
      enhancing effects of glutamate. Thus, sensitization appears to be associated with
      alterations in glutamate transmission at both the origin and termination of the
      mesoaccumbens DA pathway.

PMID- 7714802
TI  - Autoradiographic localization and characterization of [3H]alpha-trinositol (1D
      myo-inositol 1,2,6-trisphosphate) binding sites in human and mammalian tissues.
AB  - alpha-Trinositol (1D-myo-inositol 1,2,6-trisphosphate, PP56) selectively and
      potently inhibits the vasoconstrictor effects of neuropeptide Y (NPY). The
      authors used quantitative in vitro receptor autoradiography to localize and
      characterize [3H]alpha-trinositol binding sites in human and mammalian tissues.
      [3H]alpha-trinositol bound specifically to vascular and nonvascular smooth muscle
      in human, porcine and rat tissues. Binding was time dependent, reversible,
      saturable and specific for alpha-trinositol compared with inositol 1,4,5
      trisphosphate, inositol 1,3,4,5-tetrakisphosphate (Ins-1,3,4,5-P4) and inositol
      hexakisphosphate (Ins-P6). Binding to each structure gave Kd values of 5 to 20 nM
      and was consistent with a homogeneous population of sites. Binding was optimal at
      pH 5 and at low calcium concentrations. Comparison with [125I]Bolton Hunter
      labeled NPY ([125I]BH-NPY) binding in porcine tissues revealed 1) a partial
      colocalization but Bmax values for [3H]alpha-trinositol binding some two orders
      of magnitude higher than for [125I]BH-NPY and 2) failure of each of the two
      ligands to inhibit binding of the other. Comparison of [3H]alpha-trinositol with
      [3H]Ins-1,3,4,5-P4 binding in human umbilical cord revealed that both ligands
      bound specifically to vascular smooth muscle but that only [3H]Ins-1,3,4,5-P4
      bound to arterial endothelium. Both ligands bound to sites with rank orders of
      affinity Ins-1,3,4,5-P4 > Ins-P6 > inositol 1,4,5-trisphosphate. alpha-Trinositol
      had, however, three orders of magnitude higher affinity for [3H]alpha-trinositol
      than [3H]Ins-1,3,4,5-P4 binding sites; Ins-1,3,4,5-P4 and Ins-P6 had higher
      affinity for [3H]Ins-1,3,4,5-P4 binding sites. Specific [3H]alpha-trinositol
      binding sites may represent receptors by which alpha-trinositol inhibits NPY
      effects on vascular tone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714803
TI  - Comparison of the effects of evening primrose oil and triglycerides containing
      gamma-linolenic acid on nerve conduction and blood flow in diabetic rats.
AB  - The aim was to ascertain whether the ability of evening primrose oil (EPO)
      treatment to correct peripheral nerve dysfunction in streptozotocin-diabetic rats
      depends on a gamma-linolenic acid (GLA)-containing triglyceride constituent, di
      linolein mono-gamma-linolenate (DLMG). A second objective was to investigate
      whether the triglyceride conformation of GLA affects efficacy, using tri-gamma
      linolenate (TGLA), which is not present in EPO. Third, we examined the actions of
      these omega-6 essential fatty acid-containing oils on sciatic nerve blood flow to
      establish a common mechanism. After 6 weeks of diabetes, sciatic motor nerve
      conduction velocity (NCV) was 21% reduced. EPO treatment caused dose-dependent
      increases in NCV that reached asymptote within 7 days. DLMG and TGLA, at doses
      matched for GLA content, had effects indistinguishable from those of EPO. Sciatic
      blood flow, 47.2% reduced by diabetes, was partially normalized by EPO, DLMG and
      TGLA. In contrast, sunflower oil (which does not contain GLA) did not alter NCV
      or blood flow. The data therefore provide strong evidence that DLMG is the active
      component of EPO and suggest that correction of nerve dysfunction involves a
      vascular action. The precise triglyceride configuration of GLA does not appear
      crucial to its effects in experimental diabetic neuropathy.

PMID- 7714804
TI  - Prenatal exposure to cocaine selectively reduces D1 dopamine receptor-mediated
      activation of striatal Gs proteins.
AB  - The effect of in utero exposure to cocaine on striatal dopamine receptors was
      assessed at postnatal days 10 through 100 by examining receptor-mediated
      increases in GTP binding to G alpha proteins. Pregnant Dutch-belted rabbits were
      injected with 4 mg/kg i.v. of cocaine HCl twice a day on gestational days 8
      through 29, and striatal membranes were prepared from their progenies on days 10
      through 100. Dopamine-stimulated [35S]GTP gamma S binding to membrane alpha
      subunits was measured and found to increase binding to G alpha s and G alpha i.
      Pharmacological characterization of the dopamine response revealed that enhanced
      [35S]GTP gamma S binding to G alpha s is associated with D1 receptor stimulation,
      whereas binding to G alpha i is linked to D2 receptor activation. The abilities
      of dopamine to stimulate the binding of [35S]GTP gamma S to G alpha s but not to
      G alpha i was reduced in striata obtained from cocaine-exposed animals when
      examined at 10, 50 or 100 days of age. Similarly, prenatal cocaine exposure also
      reduced dopamine-stimulated [alpha-32P]GTP binding to G alpha s without
      influencing binding to G alpha i. Fetal cocaine exposure did not change carbachol
      induced increases in [35S]GTP gamma S binding to G alpha i and G alpha o.
      Immunoblot analyses showed no changes in the amounts of these alpha subunits in
      membranes from cocaine-exposed animals vs. controls. Moreover, prenatal cocaine
      did not affect [3H]SCH23390 binding to D1 dopamine receptors in the caudate,
      putamen or substantia nigra.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714805
TI  - Serotonin and thyrotropin-releasing hormone do not augment their effects on
      gastric motility on their microinjection into the nucleus raphe obscurus of the
      rat.
AB  - The existence of an interaction between serotonin (5-HT) and thyrotropin
      releasing hormone (TRH) in the nucleus raphe obscurus (NRO) of the rat in their
      excitatory effects on gastric motor function was examined using two different
      approaches. First, 5-HT and TRH were microinjected into the NRO alone at two
      different doses and then as a mixture in the same animals. In a second group of
      animals, both agents were microinjected in a rapid (20-30-sec interval)
      sequential order. These experiments were performed in alpha-chloralose
      anesthetized rats intragastric pressure and pyloric and greater curvature
      motility were monitored. Both 5-HT at a dose of 6 nmol and TRH at doses of 0.6
      and 15 pmol evoked significant increases in intragastric pressure. Microinjection
      of a mixture of 5-HT at a low dose of 0.6 nmol and TRH at doses of 0.6 pmol (low)
      and 15 pmol (high) resulted in significant increases in intragastric pressure
      that did not differ from the effects of TRH microinjected alone. A mixture of 5
      HT at a low dose of 0.6 nmol and TRH at a high dose of 15 pmol evoked increases
      in pyloric motility that did not differ from the effects of TRH alone and
      increases in greater curvature motility that were significantly lower than the
      effects of TRH alone at the same dose. Microinjection of a mixture of 5-HT at a
      high dose of 6 nmol and TRH at a low dose of 0.6 pmol evoked increases in
      intragastric pressure that did not differ from the effect of 5-HT alone. Rapid
      sequential microinjection of TRH at either a low dose of 0.6 pmol or the larger
      dose of 15 pmol after 5-HT (0.6 nmol) resulted in increases in intragastric
      pressure that did not differ from the response to either dose of TRH
      microinjected after vehicle. Similarly, the intragastric pressure response to 5
      HT (0.6 nmol) given after either dose of TRH was not significantly different from
      the response to 5-HT after vehicle. In summary, our study demonstrates that 5-HT
      and TRH do not augment their excitatory effects on gastric motor function on dual
      or sequential micro-injections in the NRO of the alpha-chloralose-anesthetized
      rats.

PMID- 7714806
TI  - Angiotensin II type I receptor antagonist inhibits the gene expression of
      transforming growth factor-beta 1 and extracellular matrix in cardiac and
      vascular tissues of hypertensive rats.
AB  - TCV-116 [(+/-)-(cyclohexyloxycarbony-loxy)ethyl2-ethoxy-1-[[2' -(1H- tetrazol-5
      yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate ], a nonpeptide selective
      angiotensin II type I receptor (AT1 receptor) antagonist, at the dose of 0.1, 1
      or 10 mg kg-1 day-1, was orally given to 22-week-old stroke-prone spontaneously
      hypertensive rats (SHRSP) for 10 weeks (from the age of 22-32 weeks) to examine
      the effects on gene expression of transforming growth factor-beta 1 (TGF-beta 1)
      and extracellular matrix proteins in the heart and blood vessels. Tissue
      messenger RNA (mRNA) was measured by northern blot analysis, with a specific
      complementary DNA probe. In the heart, left ventricular mRNA levels for
      fibronectin; types I, III and IV collagen; and laminin were significantly higher
      in SHRSP than control Wistar-Kyoto rats. In the mesenteric artery and aorta of
      SHRSP, TGF-beta 1 mRNA and the mentioned extracellular matrix protein mRNAs were
      increased compared with Wistar-Kyoto rats. Thus, the expression of various genes
      was up-regulated in cardiovascular tissues of SHRSP. Treatment of SHRSP with TCV
      116 suppressed the gene expression of the mentioned extracellular matrix proteins
      and TGF-beta 1 in both heart and blood vessels in a dose-dependent fashion.
      Furthermore, TCV-116 regressed cardiac hypertrophy and lessened the medial
      hypertrophy of the aorta in SHRSP. These results show that angiotensin AT1
      receptor antagonist in vivo can inhibit the gene expression of TGF-beta 1 and
      extracellular matrix proteins in hypertensive cardiovascular tissues. These
      effects may contribute to the beneficial effects of AT1 receptor antagonist on
      hypertensive cardiac hypertrophy and vascular thickening.

PMID- 7714807
TI  - Partial and full dopamine D1 agonists produce comparable increases in ventral
      pallidal neuronal activity: contribution of endogenous dopamine.
AB  - Systemic administration of the partial DA D1 agonist SKF38393 often increases the
      firing rate of neurons in the VP of rats. This study extended this finding by
      comparing responses to (+/-)SKF38393 with those produced by two D1 agonists that
      have greater intrinsic efficacy, (+/-)SKF82958 and (+/-)DHX. The role of
      endogenous DA in D1 agonist-induced effects also was examined. Extracellular
      recordings of single VP neurons were obtained in chloral hydrate-anesthetized
      male rats, to which equimolar doses of SKF38393, SKF82958 or DHX were
      administered i.v. Each of the agonists increased firing rate in about 45% of the
      neurons tested. Moreover, each agonist produced the same maximal increase in
      activity (161% to 178% of spontaneous rate). Acute decreases in synaptic DA,
      produced by either GBL or combined treatment with reserpine and AMPT, potentiated
      the maximal increase in activity evoked by SKF38393 or SKF82958. These DA
      depleting treatments did not alter the percentage of neurons that displayed this
      response to D1 agonist challenge. Low doses of the selective D1 antagonists
      SCH23390 or SCH39166 generally attenuated the agonist-induced changes in firing
      rate, supporting the conclusion that D1 receptors were activated by SKF38393,
      SKF82958 and DHX. Thus, these three D1 agonists, which produce different maximal
      increases in striatal adenylyl cyclase activity, had comparable efficacy to
      increase VP neuronal activity. A reduction in endogenous DA enhanced the D1
      agonist-induced effects, possibly through a reduction in inhibitory influences on
      VP neurons that are mediated by other DA receptor subtypes.

PMID- 7714809
TI  - Characterization of the adenosine A1 receptor-activated potassium current in rat
      locus ceruleus neurons.
AB  - The effect of adenosine on locus ceruleus neurons was investigated with
      intracellular recording in a totally submerged brain slice preparation. Bath
      application of adenosine (100 microM) hyperpolarized locus ceruleus neurons and
      inhibited their spontaneous firing; under voltage-clamp conditions, adenosine
      activated an inwardly rectifying, outward current (IAdo). The reversal potential
      of the IAdo was -110 mV and shifted by 59.2 mV per 10-fold change in external K+
      concentration, very close to the shift predicted by the Nernst equation for a
      pure K+ current. The IAdo was due to a direct postsynaptic action, because it
      persisted in low Ca++/high Mg++ media that block Ca(++)-dependent
      neurotransmitter release. The IAdo was not blocked by glibenclamide, which
      indicates that it is not mediated by ATP-dependent K+ channels. The adenosine
      activated current was concentration-dependent (10 microM-1 mM adenosine) and was
      blocked by the selective A1 antagonist 8-cyclopentyltheophylline in a competitive
      manner. Schild analysis in two neurons yielded estimates of the Kd value for 8
      cyclopentyltheophylline of 1.4 and 4.6 nM, which indicates that the IAdo is
      mediated by A1 adenosine receptors. The adenosine-induced hyperpolarization,
      inhibition of firing and activation of outward current were blocked by external
      barium, but not by 4-aminopyridine. By contrast, we have previously shown that
      adenosine enhances A-current, thereby reducing action potential duration in locus
      ceruleus neurons, and these effects are blocked by 4-aminopyridine but not
      barium. These data indicate that the adenosine-induced hyperpolarization and
      inhibition of firing are mediated by the IAdo and that these effects are
      independent of adenosine's enhancement of A-current.

PMID- 7714808
TI  - Effect of zolpidem on gamma-aminobutyric acid (GABA)-induced inhibition predicts
      the interaction of ethanol with GABA on individual neurons in several rat brain
      regions.
AB  - Previous investigations have suggested a relationship between zolpidem binding
      within specific brain regions and the ability of ethanol or zolpidem to enhance
      gamma-aminobutyric acid (GABA)-induced inhibition. The purpose of the present
      study was to extend our electrophysiological analysis to additional brain sites
      with high levels of zolpidem binding. In the brain regions chosen, red nucleus
      and globus pallidus, GABA-induced inhibition was shown to be enhanced by either
      ethanol or zolpidem on some, but not all, neurons. These findings led to the
      hypothesis that the effect of zolpidem on GABA-induced inhibition would predict
      the action of ethanol on responses to GABA for that neuron. When zolpidem and
      ethanol were applied individually to the same neurons in the red nucleus and
      globus pallidus, those neurons sensitive to zolpidem enhancement of GABA also
      were sensitive to ethanol. Conversely, if zolpidem did not enhance responses to
      GABA, ethanol did not enhance responses to GABA at these brain sites. A similar
      relationship between the abilities of zolpidem and ethanol to enhance GABA
      induced inhibition was obtained in 90% of the neurons studied in the medial
      septum/diagonal band and ventral pallidum. These studies provide further support
      for the contention that the zolpidem-sensitive GABAA-benzodiazepine isoreceptor
      also responds to ethanol. Finally, the expression of GABAA subunit mRNAs was
      analyzed by polymerase chain reaction from micropunches of several brain regions
      that contain zolpidem binding sites and exhibit sensitivity to ethanol.
      Polymerase chain reaction analysis proved more sensitive than in situ
      hybridization in the detection of receptor subunit mRNAs. Several subunits (alpha
      1, alpha 2, alpha 3, beta 2, beta 3 and gamma 2) were common to all brain regions
      in which ethanol and zolpidem enhanced GABA responses. GABAA receptor alpha 4/5,
      alpha 6, beta 1, gamma 1, gamma 3 and delta subunits were not consistently
      expressed in association with the presence of zolpidem binding. These data are
      consistent with the view that one native GABAA receptor to which zolpidem binds,
      and on which ethanol acts, contains the GABAA receptor subunits alpha 1, beta 2
      and gamma 2; however, the present investigation did not preclude the possibility
      that other subunit combinations can contribute to ethanol and zolpidem
      enhancement of responses to GABA.

PMID- 7714811
TI  - Sodium channel blockers reduce oxygen-glucose deprivation-induced cortical
      neuronal injury when combined with glutamate receptor antagonists.
AB  - Blockers of voltage-gated Na+ channels can protect central neuronal axons from
      hypoxic injury in vitro but have shown limited neuroprotective effects on
      neurons, where substantial injury is mediated by glutamate receptors. We explored
      the ability of several voltage-gated Na+ channel blockers to protect murine
      cultured cortical neurons from injury induced by oxygen-glucose deprivation.
      Whole-cell recordings from neurons revealed two types of Na+ currents activated
      by membrane depolarization: one rapidly inactivating and the other
      noninactivating. Both currents were blocked by tetrodotoxin (TTX) and 5,5
      diphenylhydantoin (phenytoin). Fluorescent imaging using the Na(+)-selective dye
      SBFI confirmed that TTX attenuated the increase in intracellular free Na+ induced
      by oxygen-glucose deprivation. Addition of TTX (1 microM) but not phenytoin (10
      100 microM) produced a small and variable reduction in neuronal death subsequent
      to oxygen-glucose deprivation for 40 to 50 min. Blockade of glutamate
      neurotoxicity by combined addition of MK-801, 7-chlorokynurenate and 6-cyano-7
      nitroquinoxaline-2,3-dione markedly reduced injury such that prolonged
      deprivation times (75-100 min) were needed to induce widespread neuronal death.
      In this setting of glutamate receptor blockade, addition of TTX, phenytoin or one
      of several other Na+ channel blockers--lidocaine (100 microM), QX-314 (1 mM),
      quinidine (100 microM) or lorcainide (10 or 100 microM)--all further reduced
      neuronal death. Present results raise the possibility that Na+ channel blockers
      may be useful in protecting gray matter from hypoxic-ischemic injury, especially
      when combined with antiexcitotoxic approaches.

PMID- 7714810
TI  - Differential toxicity of the protein phosphatase inhibitors microcystin and
      calyculin A.
AB  - Microcystin (Mcyst) and calyculin A (CalA) in vitro inhibit protein phosphatases
      (PP)1 and 2A activity (IC50 0.1-2.0 nM). This study was aimed at determining the
      contribution of PP inhibition to Mcyst hepatotoxicity by comparing the effect of
      these two chemically different inhibitors in perfused rat livers. Both compounds
      (60 micrograms Mcyst and 6 micrograms CalA/150 ml perfusate) caused cessation of
      bile flow and inhibition of PP activity after 20 min of perfusion to 8% and 37%
      of control activity for Mcyst and CalA treatments, respectively.
      Histopathological findings included loss of cord sinusoidal pattern and of normal
      liver architecture. There also was hepatocyte swelling, pyknotic changes and
      necrosis. Mcyst caused a modest increase in perfusion pressure of 1.2 cm of
      water, whereas CalA caused a 3-fold increase. The most likely explanation for
      this hemodynamic effect is direct action of CalA on the vascular endothelium
      and/or sinusoidal and perisinusoidal cells. This possibility was explored with
      hepatocytes and sinusoidal endothelial cells. PP activity of both cell types was
      inhibited by 10 to 100 nM CalA followed later by cell lysis, whereas Mcyst (500
      nM-2 microM) had no effect on sinusoidal endothelial cells, but inhibited PP
      activity and caused later lysis in hepatocytes (Mcyst 20-160 nM). Mcyst
      hepatotoxicity is therefore a direct consequence of PP inhibition in hepatocytes,
      the loss of sinusoidal integrity following from the primary toxic insult to the
      hepatocyte. Inhibition of PP activity of the cells of the presinusoidal
      vasculature and/or nonparenchymal cells results in hepatic hypertension.

PMID- 7714812
TI  - Renal vascular and tubular actions of calcitonin gene-related peptide: effect of
      NG-nitro-L-arginine methyl ester.
AB  - The existence of calcitonin gene-related peptide (CGRP) nerve fibers and CGRP
      receptors in the kidney and the coupling of the receptors to adenylyl cyclase
      suggest that CGRP participates in renal regulation. This study investigates the
      dose-effect relationship of CGRP on renal blood flow (RBF) and arterial
      conductance, glomerular filtration rate (GFR) and tubular excretion in Inactin
      anesthetized, Sprague-Dawley rats. The contributions of endothelium-derived
      relaxing factor/nitric oxide in the renal actions of CGRP also were investigated
      via renal arterial injection of the nitric oxide synthase inhibitor, NG-nitro-L
      arginine methyl ester (L-NAME, 0.5 or 5 mg/kg). Renal arterial infusion of CGRP
      (0.3-300 pmol/kg/min) did not affect mean arterial pressure or heart rate. Low
      doses of CGRP increased RBF, arterial conductance and GFR, but the highest dose
      reduced RBF and conductance without affecting GFR. High doses of CGRP also
      increased urine flow and excretions of Na+ and K+. The renal vasodilator but not
      the constrictor effect of CGRP was inhibited by both doses of L-NAME. The
      increase in GFR by the lowest dose of CGRP was attenuated by the low dose and
      abolished by the high dose of L-NAME. L-NAME did not inhibit the diuretic,
      natriuretic and kaliuretic effects elicited by high doses of CGRP. The results
      show that a low dose of CGRP causes renal vasodilatation via the release of
      endothelium-derived relaxing factor/nitric acid.

PMID- 7714813
TI  - Pulmonary CYP2E1 bioactivates 1,1-dichloroethylene in male and female mice.
AB  - Pulmonary cytotoxicity induced by 1,1-dichloroethylene (DCE) has been linked to
      the generation of reactive intermediates through a cytochrome P450-dependent
      pathway. In the present studies, our objectives were to investigate and compare
      cytochrome P450 isozyme-selective bioactivation of DCE in vitro in the lungs of
      male and female mice. Our results showed that CYP2E1-dependent p-nitrophenol
      hydroxylation was significantly higher in microsomes from female (0.45 +/- 0.01
      nmol/mg protein/min) than from male (0.38 +/- 0.02 nmol/mg protein/min) mice.
      Lung microsomes from male mice incubated in the presence of an NADPH-generating
      system and increasing amounts of DCE (5-20 mM) exhibited corresponding decreases
      in p-nitrophenol hydroxylase activity (19%-50%); however, greater decreases (26%
      70%) were observed in lung microsomes from female mice incubated under the same
      conditions. In contrast, alterations in CYP2B1-dependent 7-pentoxyresorufin O
      dealkylation and CYP1A1-dependent 7-ethoxyresorufin O-dealkylation were not
      detected in any microsomal preparation incubated with DCE. Reaction with an anti
      CYP2E1 antibody abolished the inhibition of p-nitrophenol hydroxylation by DCE.
      Protein immunoblotting revealed significant decreases in the intensity of the
      bands of microsomal samples incubated previously with DCE; in contrast,
      alterations in heme content were not evoked by reaction with DCE. Our results
      have demonstrated that CYP2E1, and not CYP2B1 or CYP1A1, mediated the
      bioactivation of DCE. Furthermore, this bioactivation occurred to a greater
      extent in lung microsomes from female than from male mice, which suggests that
      females may be at slightly greater risk for DCE-induced pneumotoxicity.

PMID- 7714814
TI  - Carvedilol, a new beta-adrenoreceptor blocker, vasodilator and free-radical
      scavenger, exerts an anti-shock and endothelial protective effect in rat
      splanchnic ischemia and reperfusion.
AB  - Splanchnic artery occlusion (SAO) followed by reperfusion results in circulatory
      shock in which oxygen-derived free radicals play an important role. Carvedilol, a
      novel beta adrenoceptor antagonist and a vasodilator, has been recently shown to
      exert potent antioxidant effects in multiple cell model systems. In the present
      experiment, we investigated the effect of carvedilol on SAO shock. Pentobarbital
      anesthetized rats were subjected to 60 min of SAO followed by 120 min of
      reperfusion. Administration of 1 mg/kg carvedilol 10 min before reperfusion
      prolonged survival time (P < .05) and attenuated the increases in tissue
      myeloperoxidase activities (P < .01) and hematocrits (P < .001). Moreover,
      carvedilol significantly preserved superior mesenteric artery endothelial
      function (P < .01). Similar protection was seen in SAO shock rats treated with
      the superoxide free-radical scavenger superoxide dismutase. Except for a moderate
      attenuation of an increase in hematocrits, protective effects were not seen in
      SAO shock rats treated with the prototypic beta blocker propranolol. These
      results indicate that in murine SAO shock, carvedilol affords significant
      protection, which may be achieved through maintenance of tissue blood perfusion,
      quenching of oxygen free radicals, preservation of vascular endothelial function,
      and inhibition of neutrophil-endothelial interaction and its resultant increased
      microvascular permeability.

PMID- 7714815
TI  - Differential effects of direct and indirect dopamine agonists on the induction of
      gnawing in C57Bl/6J mice.
AB  - The ability of indirect dopamine agonists to induce gnawing in male C57Bl/6J mice
      was compared to that of direct dopamine agonists acting at dopamine D1 or D2
      receptor subtypes. Holes left by the mice on the corrugations of packing
      cardboard were used as an objective index of gnawing. Indirect dopamine agonists,
      including dopamine releasers such as fencamfamine, (+)-amphetamine and amfenolic
      acid and dopamine uptake inhibitors such as cocaine, GBR 12909 (1-[2-[bis(4
      fluorophenyl)methoxy]ethyl]-4-[3- phenylpropyl]piperazine diHCl) and nomifensine
      produced dose-dependent increases in gnawing. None of the direct agonists (e.g.,
      apomorphine, quinpirole or SKF 82958 [(+/-)-6-chloro-7,8-dihydroxy-3-allyl-1
      phenyl-2,3,4,5-tetrahydro- 1H-3-benzazepine]) increased gnawing. Although these
      compounds varied in potency and efficacy, 18 structurally diverse compounds
      induced gnawing in 100% of the mice tested. Four weak indirect agonists (3,4
      methyl-enedioxymethamphetamine, amantadine, 2-phenylethylamine and benztropine)
      failed to induce gnawing. The lack of efficacy of postsynaptic dopamine agonists
      was not changed by various combinations of postsynaptic agonists (e.g., dopamine
      D1 and D2 agonists in combination). Nonetheless, the dopaminergic nature of the
      gnawing response was confirmed in experiments in which a host of compounds with
      primary actions at nondopaminergic sites did not induce gnawing; compounds
      included nicotine, caffeine, dizocilpine, lidocaine, fluoxetine and nisoxetine.
      In addition, both the dopamine D1 antagonist SCH 23390 [R-(+)-7-chloro-8-hydroxy
      3-methyl-1-phenyl-2,3,4,5-tetrahydro- 1H-3-benzazepine], the D2 antagonist
      eticlopride and the dopamine D1/D2 antagonist flupenthixol produced dose
      dependent blockade of gnawing induced by either cocaine or
      methylphenidate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714816
TI  - Site-selective effect of bicarbonate on amantadine renal transport: quinine
      sensitive in proximal vs quinidine-sensitive sites in distal tubules.
AB  - The mechanism for bicarbonate enhancement of amantadine (A+) uptake was studied
      further. A selective modulatory effect of bicarbonate on the stereoselectivity of
      inhibition of A+ uptake by the stereoisomers, quinine (Q) and quinidine (QD), as
      reflected by the reversal of potency (Q > QD in KHS vs. QD > Q in phosphate), is
      reported. Studies were performed in bicarbonate (KHS) and phosphate buffers using
      purified cortical proximal (PT) and distal tubules (DT) from rat kidneys.
      Variations of extracellular K+ and Ca++ were used to assess the effect of
      membrane depolarization and calcium on A+ uptake by the tubules. K+ concentration
      manipulation (1.5-100 mM) did not change A+ uptake by PT or DT in KHS buffer.
      High Ca++ (5.0 mM) decreased A+ uptake by PT in KHS (P < .001), whereas in
      phosphate buffer, both 2.5 and 5.0 mM Ca++ decreased uptake (P < .001). In DT,
      0.25 mM Ca++ enhanced A+ uptake (P < .05) in KHS, but 2.5 and 5.0 mM Ca++
      decreased it in both buffers. Inhibition studies with Q and QD were performed to
      characterize the bicarbonate-dependent and bicarbonate-independent A+ transport
      sites further. Stereoselectivity of inhibition was observed in PT in all buffers
      used. Potency of Q was higher than QD in KHS but lower than QD in phosphate
      buffered PT. QD potency remained unchanged. In phosphate-plus-bicarbonate
      buffered PT, the inhibitory potencies for Q and QD increased, with the potency of
      QD being greater than in KHS (P < .001). For DT, Q and QD were equipotent in all
      buffers used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714817
TI  - Heparin attenuates the effect of mitogenic vasoconstrictors on mesangial cell
      proliferation and handling of immunoglobulin G complexes.
AB  - Angiotensin II (ANG II) and endothelin-1 (ET-1) may both play significant roles
      in causing mesangial expansion and glomerulosclerosis after renal injury by
      enhancing mesangial cell (MC) proliferation and by increasing MC uptake of
      macromolecules. Heparin has been demonstrated to significantly ameliorate the
      development of glomerulosclerosis in animal models of progressive renal injury,
      although the mechanism is unknown. We undertook the present study to examine in
      an in vitro system the mechanism by which heparin might modulate the effects of
      ANG II and ET-1 on MC proliferation and MC uptake of immunoglobulin G (IgG)
      complexes. Heparin was found to suppress MC uptake of IgG complexes in a
      concentration-related manner. Whereas ANG II significantly enhanced (P < .01)
      uptake of IgG complexes, this increase was significantly antagonized (P < .01) by
      coincubation of MC with heparin at therapeutic concentration (1 U/ml). ET-1 also
      was found to significantly increase MC uptake of IgG complexes (P < .02), and
      this increase also was significantly antagonized by coincubation with heparin (P
      < .02). Heparin was found to inhibit surface binding of IgG to MC in a
      concentration-related manner (55% reduction at 1 U/ml). MC [3H]thymidine
      incorporation was significantly enhanced by both ANG II (P < .01) and ET-1 (P <
      .001) and these mitogenic effects were significantly attenuated by coincubation
      of cells with heparin (P < .01 and P < .001, respectively).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7714818
TI  - Enantioselective disposition of ibuprofen in elderly persons with and without
      renal impairment.
AB  - By using stable isotope methodology, we studied the disposition of ibuprofen
      after the first and last dose of a 4-week regimen of 800 mg of racemic ibuprofen
      every 8 hr in three groups of subjects: 1) young healthy volunteers (n = 8); 2)
      healthy elderly volunteers (n = 14); and 3) elderly patients with creatinine
      clearance between 30 and 70 ml/min (n = 13). Stereoselective gas chromatography
      mass spectrometry was used to quantify deuterated S- and nondeuterated R- and S
      ibuprofen in serum up to 24 hr after the first and last doses. Urinary excretion
      of the stereoisomeric forms of carboxyibuprofen, hydroxyibuprofen and ibuprofen
      glucuronide were determined up to 24-hr postdose by stereoselective high
      performance liquid chromatography. Stereoselective serum protein binding was
      determined by ultrafiltration. Both elderly groups had significantly decreased
      binding of S-ibuprofen compared to the young group. The S-ibuprofen
      pharmacokinetics were significantly different in the elderly patients with renal
      impairment compared to the young volunteers: the T1/2 was increased, the unbound
      clearance was decreased and the unbound concentration at steady state was
      increased. Fraction inverted was similar for all groups, but unbound clearances
      of glucuronidation and hydroxylation were reduced in the elderly patients with
      renal impairment. These results suggest that the disposition of ibuprofen
      enantiomers is altered in elderly persons with renal impairment; these changes
      may increase the risk for nonsteroidal anti-inflammatory drug-associated adverse
      effects in such patients.

PMID- 7714819
TI  - Dissociation of tissue thiols content from nitroglycerin-induced cyclic-3',5'
      guanosine monophosphate and the state of tolerance: in vivo experiments in rats.
AB  - The in vivo effects of nitroglycerin (GTN) on the biochemical response [cyclic
      3',5'-guanosine monophosphate (cGMP) levels] of vascular (aorta and inferior vena
      cava, IVC) and other tissues (heart and lung) were studied. GTN caused dose and
      time-dependent increases in cGMP content of aorta and IVC. Compared to base line,
      maximal concentrations of 3- to 4-fold the basal levels of cGMP were measured in
      the aorta, IVC and lung of rats after 2 mg i.v. bolus doses of GTN. Tolerance to
      GTN, as assessed by the reduction in the cGMP increase in response to an i.v. GTN
      dose, developed 12 to 18 hr after continuous i.v. infusion (100-200
      micrograms/hr) of the drug. Significant differences in the pattern of formation
      and degradation of cGMP were noted between tolerant and nontolerant rats. Unlike
      the control IVC tissue, where elevated cGMP was measured throughout the 5-min
      post GTN administration, in tolerant IVC, cGMP levels were not significantly
      different from the basal values at time points 3 and 5 min post GTN. These
      results suggest that IVC is more prone to (or less recoverable from) the state of
      tolerance than the aorta. Furthermore, when tissue thiols were measured in
      control and tolerant rats, a complete dissociation was observed between the state
      of tolerance and the endogenous glutathione and cysteine concentrations. These
      data constitute strong evidence against an in vivo depletion of tissue thiols as
      being the primary determinant underlying the development of tolerance during
      nitrate therapy.

PMID- 7714820
TI  - Factors controlling changes in intracellular Ca2+ concentration produced by
      noradrenaline in rat mesenteric artery smooth muscle cells.
AB  - 1. The intracellular Ca2+ concentration ([Ca2+]i) was measured in mesenteric
      artery smooth muscle cells using the fluorescent indicator indo-1. 2.
      Noradrenaline (1-10 microM) produced a transient increase in [Ca2+]i. This
      response was unaffected by the removal of external calcium suggesting that the
      bulk of the increase in [Ca2+]i produced by noradrenaline is due to release from
      an intracellular store. 3. The maintained application of caffeine (10 mM)
      produced a transient rise in [Ca2+]i. The rate of relaxation was slower than that
      of the noradrenaline response. If caffeine was removed at the peak of the rise in
      [Ca2+]i then [Ca2+]i recovered more quickly than was the case in both the
      maintained response to noradrenaline and that to caffeine. 4. In the presence of
      noradrenaline, caffeine or thapsigargin elevated [Ca2+]i. However, if
      thapsigargin or caffeine was added first, the subsequent application of
      noradrenaline did not increase [Ca2+]i, suggesting that only part of the caffeine
      sensitive store is sensitive to noradrenaline. 5. The recovery of [Ca2+]i during
      the application of caffeine was unaffected by the removal of external sodium
      suggesting that Na+-Ca2+ exchange is not important in the reduction in [Ca2+]i.
      The addition of lanthanum (1 mM) did, however, greatly slow [Ca2+]i recovery. 6.
      We conclude that the three major factors responsible for removing Ca2+ ions from
      the cytoplasm are: (i) a caffeine- and noradrenaline-sensitive store (43%), (ii)
      a caffeine-sensitive but noradrenaline-insensitive store (36%), and (iii) a
      sarcolemmal Ca(2+)-ATPase (16%). Finally, a 5% contribution remains to be
      accounted for.

PMID- 7714821
TI  - Ca2+ influx during agonist and Ins(2,4,5)P3-evoked Ca2+ oscillations in HeLa
      epithelial cells.
AB  - 1. Histamine-stimulated [Ca2+]i oscillations were studied in > 162 HeLa cells
      using the techniques of Ca2+ imaging, patch clamp and single-cell indo-1
      fluorescence. 2. [Ca2+]i oscillations in HeLa cells were acutely dependent on
      extracellular Ca2+ and were also blocked by the extracellular addition of Cd2+
      (100 microM). The Mn2+ quench technique, using fura-2 fluorescence, demonstrated
      that agonist-stimulated Ca2+ oscillations were associated with an increase in
      plasma membrane Mn2+ permeability. However, no cyclic fluctuations in Mn2+ influx
      were resolved over the period of [Ca2+]i spiking. 3. In whole-cell patch clamped
      cells an imposed potential of +80 mV was shown to block the thapsigargin-induced
      Ca2+ influx. Histamine and Ins(2,4,5)P3-induced [Ca2+]i oscillations were tested
      for the phase dependence on extracellular Ca2+ by rapidly switching the membrane
      potential to +80 mV, reversibly blocking Ca2+ influx. Ca2+ spikes were abolished
      by steps to +80 mV made at the point of spike initiation but not by steps made
      after development of the rapid rising phase of the spike. Steps of membrane
      potential to +80 mV, for increasing periods of time during the interspike period,
      increased the latency to the next [Ca2+]i spike by up to a maximum of
      approximately 150% of the control interspike interval. 4. It is concluded that
      the extracellular Ca2+ dependence of the histamine-induced [Ca2+]i oscillations
      is due to a crucial role of Ca2+ influx during spike initiation and an additional
      important role in setting the interspike interval. The results obtained can be
      interpreted in terms of a constant stimulated Ca2+ influx during [Ca2+]i spiking.

PMID- 7714822
TI  - Inhibition of acetylcholine release from mouse motor nerve by a P-type calcium
      channel blocker, omega-agatoxin IVA.
AB  - 1. The effects were studied of the central neurone P-type Ca2+ channel blockers,
      omega-agatoxin IVA, omega-conotoxin MVIIC (polypeptide toxins) and synthetic
      funnel-web spider polyamine toxin on acetylcholine release from mouse motor
      nerve. 2. omega-Agatoxin IVA decreased the quantal content of endplate potentials
      and blocked synaptic transmission in the nanomolar range in a reversible manner,
      whereas the other toxins depressed transmission in the hundred micromolar range.
      3. The polyamine toxin, but not the polypeptide toxins, decreased the amplitude
      of the miniature endplate potential. The increase in the frequency of miniature
      endplate potentials evoked by high [K+], but not that evoked by alpha-latrotoxin,
      was effectively antagonized by omega-agatoxin IVA. 4. In the presence of omega
      agatoxin IVA, high frequency nerve stimulation produced facilitation of endplate
      currents and tetanic contractions. 5. The results suggest that, under
      physiological conditions, the Ca2+ necessary for nerve action potential-evoked
      acetylcholine release is translocated via a subtype of the P-type Ca2+ channel
      sensitive to omega-agatoxin IVA.

PMID- 7714823
TI  - Activation of Ca(2+)-dependent Cl- currents in cultured rat sensory neurones by
      flash photolysis of DM-nitrophen.
AB  - 1. Voltage-gated Ca2+ currents (ICa) and Ca(2+)-activated Cl- currents (ICl(Ca))
      were recorded from cultured rat dorsal root ganglion (DRG) neurones using the
      whole-cell configuration of the patch clamp technique. Intracellular photorelease
      of Ca2+ by flash photolysis of DM-nitrophen elicited transient inward currents
      only in those cells which possessed Ca(2+)-activated Cl- tail currents following
      ICa. The reversal potential of the flash responses was hyperpolarized when
      extracellular Cl- was replaced by SCN-. The flash responses and the Ca(2+)
      activated Cl- tail currents were inhibited by the Cl- channel blockers niflumic
      acid (10-100 microM) and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) (10
      microM). 2. After activation by ICa, the Ca(2+)-activated Cl- current could be
      reactivated during its decay by photorelease of caged Ca2+. Experiments carried
      out on neurones held at 0 mV demonstrated that ICl(Ca) could be chronically
      activated due to residual Ca2+ influx. These data directly demonstrated that the
      decay of ICl(Ca) is not due to inactivation but rather to deactivation as a
      result of removal of the Ca2+ load from the cell cytoplasm. 3. Photorelease of
      caged inositol 1,4,5-trisphosphate (IP3) failed to activate any Ca(2+)-dependent
      current responses in cultured DRG neurones, although application of caffeine
      elicited transient inward currents, and responses to photoreleased IP3 could be
      obtained from freshly dissociated smooth muscle cells. 4. Photorelease of Ca2+
      provides a useful method for investigating the properties of ICl(Ca)
      independently from other physiological parameters. In addition, we have directly
      demonstrated that ICl(Ca) in DRG neurones does not inactivate, and so may
      continue to modulate membrane excitability as long as the intracellular Ca2+
      concentration ([Ca2+]i) close to the cell membrane is elevated.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7714824
TI  - AMPA receptors with high Ca2+ permeability mediate synaptic transmission in the
      avian auditory pathway.
AB  - 1. The permeability of AMPA (alpha-amino-3-hydroxy-5-methyl-4-
      isoxazolepropionate) receptors in the chick cochlear nucleus, the nucleus
      magnocellularis (nMAG), was examined by measuring the shift in reversal potential
      (Erev) of current through glutamate or neurotransmitter-gated channels in
      solutions of different ionic composition. 2. Outwardly rectifying glutamate
      activated currents in outside-out membrane patches showed rapid activation and
      desensitization. The Erev of glutamate-evoked current in zero sodium solutions
      was dependent on the extracellular Ca2+ concentration. The relation between Erev
      and Ca2+ ionic activities could be described by the Goldman-Hodgkin-Katz equation
      with a permeability ratio, PCa/PCs, of 3.3. The PNa/PCs was estimated as 0.66,
      indicating a PCa/PNa of 5. 3. Evoked excitatory postsynaptic currents (EPSCs)
      could be recorded during local perfusion of the auditory nerve-nMAG synapse with
      isotonic Ca2+. The Erev of the EPSC shifted in the positive direction in high
      Ca2+ solution as predicted from the preceding analysis. The fraction of current
      carried by Ca2+ during the AMPA receptor EPSC was estimated as 18%.

PMID- 7714825
TI  - Nicotinamide-adenine dinucleotide regulates muscarinic receptor-coupled K+ (M)
      channels in rodent NG108-15 cells.
AB  - 1. The possible role of nicotinamide-adenine dinucleotide (NAD+) and cyclic
      adenosine diphosphate ribose (cADPR) as regulators of M-type K+ currents (IK(M))
      has been studied in whole-cell patch-clamped NG108-15 mouse neuroblastoma x rat
      glioma cells that had been transformed to express m1 muscarinic acetylcholine
      receptors (mAChRs). 2. Pre-incubation of NG108-15 cells for 6-8 h with
      streptozotocin (2-5 mM) reduced NAD+ levels by 40-50%. Nicotinamide (2-5 mM)
      increased NAD+ levels and prevented depletion by streptozotocin. 3.
      Streptozotocin pretreatment reduced the inhibition of IK(M) produced by 100
      microM acetylcholine (ACh) from 51.6 +/- 7.0 to 29.1 +/- 7.5%. This was prevented
      by simultaneous pre-incubation with 2 mM nicotinamide or by adding 2 mM NAD+ to
      the pipette solution. Neither procedure significantly affected the initial
      amplitude of IK(M). 4. Inclusion of 2 microM cADPR in the pipette solution
      induced a slow loss of IK(M) with a time constant of about 20 min. 5. It is
      concluded that mAChR-induced inhibition of IK(M) requires intracellular NAD+.
      This might be needed for the formation of cADPR as a regulator or messenger for
      IK(M) inhibition.

PMID- 7714826
TI  - Suppression of GABAA receptor responses by NMDA application in hippocampal
      neurones acutely isolated from the adult guinea-pig.
AB  - 1. In acutely isolated hippocampal cells, NMDA and glutamate application
      suppressed GABAA receptor-mediated responses. We studied the cellular events
      underlying the interaction between the two classes of receptors by using a whole
      cell voltage-clamp approach. 2. Following an NMDA application, an outward current
      mediated by GABAA receptor activation (GABA response) was suppressed for up to 12
      s. The suppression of the GABA response was reduced when Ca2+ in the
      extracellular solution was replaced by Ba2+ or when intracellular BAPTA (1,2
      bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) was increased from 1 to 10
      mM. 3. Replacing ATP in the intracellular solution by adenosine-5'-O-3
      thiotriphosphate reduced the suppressive effect of NMDA application on the GABA
      response. Okadaic acid, a phosphatase inhibitor, also prevented the NMDA-induced
      suppression of the GABA response. In addition, when the intracellular perfusing
      solution contained the calcineurin autoinhibitory fragment (50 microM),
      suppression of the GABA response by the NMDA current was also reduced. 4.
      Intracellular perfusion of an activated form of the Ca(2+)-dependent phosphatase,
      calcineurin, suppressed GABA responses. 5. The results show that NMDA responses
      elicited in hippocampal neurones transiently suppressed GABA responses. The data
      suggest that the functional linkage of the NMDA response with the GABA response
      was established via a Ca(2+)-dependent dephosphorylation process.

PMID- 7714828
TI  - Effects of neurotensin on rat supraoptic nucleus neurones in vitro.
AB  - 1. The electrophysiological actions of neurotensin on magnocellular
      neurosecretory cells (MNCs) were examined during intracellular recording from
      seventy-three supraoptic nucleus neurones in superfused explants of rat
      hypothalamus. 2. Application of neurotensin tridecapeptide (NT(1-13); 1 nM to 3
      microM) caused a membrane depolarization and reversibly attenuated the after
      hyperpolarization (AHP) which followed current-evoked spike trains. This effect
      was accompanied by increased firing frequency during depolarizing current pulses
      evoked from a fixed potential. 3. The effects of neurotensin could be mimicked by
      the C-terminal fragment, NT(8-13), but not by the N-terminal fragment, NT(1-8).
      4. Depolarizing responses to NT(1-13) or NT(8-13), retained during K+ channel
      blockade with internal Cs+, were accompanied by increased membrane conductance.
      Current- and voltage-clamp analyses revealed that neurotensin-evoked
      depolarizations result partly from the activation of a non-selective cationic
      conductance reversing near -34 mV. 5. Depolarizing responses to neurotensin were
      retained in the presence of TTX or in Ca(2+)-free solutions, indicating the
      involvement of receptors located on the plasma membrane of MNCs themselves. 6.
      Through these effects endogenously released neurotensin may modulate
      excitability, activity patterns and secretion from the hypothalamo
      neurohypophysial axis.

PMID- 7714827
TI  - Baclofen enhancement of acetylcholine release from amacrine cells in the rabbit
      retina by reduction of glycinergic inhibition.
AB  - 1. The mechanism by which the GABAB-receptor agonist, baclofen, enhances the
      light-evoked release of [3H]acetylcholine (ACh) from cholinergic amacrine cells
      was studied using an eye-cup preparation in anaesthetized rabbits and isolated
      retinas. 2. When applied locally to the rabbit retina, baclofen increased the
      release of ACh evoked by a flickering light (3 Hz) by over 40%. 3. In isolated
      retinas, baclofen strikingly inhibited the K(+)-evoked release of glycine but had
      no effect on GABA release. 4. In the rabbit eye cup, strychnine enhanced the
      light-evoked release of ACh to a similar degree to that produced by baclofen. The
      effects of baclofen and strychnine on the light-evoked release of ACh were not
      additive. In contrast, bicuculline did not affect the enhancing action of
      baclofen on the light-evoked release of ACh. 5. In order to see whether the
      glycinergic amacrine cells might be stimulated by ACh, isolated rat and rabbit
      retinas were exposed to muscarine. This cholinergic agonist potentiated the K(+)
      evoked release of glycine by 54%. 6. We suggest that baclofen enhances the light
      evoked release of ACh from amacrine cells by inhibiting glycine release from
      glycinergic amacrine cells which are stimulated by ACh and form an inhibitory
      feedback loop to the cholinergic neurones.

PMID- 7714830
TI  - Absence of mechanical evidence for attached weakly binding cross-bridges in frog
      relaxed muscle fibres.
AB  - 1. Passive force responses to ramp stretches at various velocities were measured
      in intact and skinned single muscle fibres isolated from the lumbricalis muscle
      of the frog. Force was measured using a fast capacitance transducer and sarcomere
      length was measured using a laser light diffraction technique at a point very
      close to the fixed end so as to avoid effects of fibre inertia. Experiments were
      performed at 15 degrees C with sarcomere length between 2.13 and 3.27 microns
      under high (170 mM) and low (20 mM) ionic strength. 2. The analysis shows that
      the force response is the sum of at least three components: (i) elastic (force
      proportional to the amount of stretch), (ii) viscous (force proportional to rate
      of stretch), and (iii) viscoelastic (resembling the response of a pure viscous
      element in series with an elastic element). 3. The amplitude of all these
      components increased progressively with sarcomere length in the whole range
      measured. 4. A further component, attributable to the short-range elasticity
      (SREC), was present in the force response of the intact fibres. 5. The amplitude
      of the force response decreased substantially upon skinning at high ionic
      strength but increased again at low ionic strength. The SREC was completely
      abolished by skinning. 6. None of the components of the force response was found
      to have the properties expected from the previously postulated 'weakly binding
      bridges'.

PMID- 7714829
TI  - Reduced maximum shortening velocity in the absence of phosphocreatine observed in
      intact fibres of Xenopus skeletal muscle.
AB  - 1. ADP inhibits the maximum shortening velocity (V0) in skeletal muscle. [ADP]
      may increase considerably during contractions and reduce V0 in the absence of
      energy buffering by phosphocreatine (PCr). We have tested this hypothesis by
      comparing V0 in long and short tetani produced in situations where PCr buffering
      is absent. 2. Single, intact muscle fibres were dissected from toe muscles of
      Xenopus and stimulated by current pulses at 20 degrees C. The test sequence
      consisted of a 400 ms tetanus, followed after 3 s by a 1400 ms tetanus and after
      an additional 4 s by a 400 ms tetanus. V0 was measured with slack tests at 200
      and 1200 ms, respectively. 3. The PCr system was inactivated in three ways: (i)
      fatiguing fibres with repeated short tetani; (ii) inhibition of the creatine
      kinase (CK) reaction with dinitrofluorobenzene; and (iii) inhibition of energy
      metabolism with iodoacetic acid and cyanide. 4. Under control conditions V0 was
      similar in all three test tetani. With inactive PCr buffering V0 was about 30%
      lower in the long tetanus. This slowing recovered fully in the second short
      tetanus in fatigue and with CK inhibition. 5. Calculations suggest that [ADP] can
      reach very high levels (about 3 mM) during prolonged contractions in the absence
      of PCr buffering.

PMID- 7714831
TI  - Evidence for a critical role of nitric oxide in the tonic excitation of rabbit
      renal sympathetic preganglionic neurones.
AB  - 1. A large proportion of sympathetic preganglionic neurones contain nitric oxide
      synthase. The purpose of this study was to determine the effects of facilitation
      and inhibition of nitric oxide synthesis within the lower thoracic spinal cord
      (which contains the majority of renal preganglionic neurones) on renal
      sympathetic nerve activity (rSNA). 2. In anaesthetized rabbits, rSNA was recorded
      before and after intrathecal injection (50 microliters of 0.5 M solution) of
      either L-arginine, a precursor of nitric oxide, or N omega-nitro-L-arginine
      methyl ester (L-NAME), an inhibitor of nitric oxide synthase, into the lower
      thoracic spinal cord. Spinal cord sections were also stained for the presence of
      NADPH diaphorase, a marker of nitric oxide synthesizing neurones. 3. A high
      density of NADPH diaphorase-containing neurones was found within the
      intermediolateral cell column of the lower thoracic spinal cord. 4. Intrathecal
      injection of L-arginine and L-NAME resulted in a large increase (113 +/- 25%) and
      decrease (43 +/- 8%), respectively, in rSNA. In contrast, injection of the
      inactive isomers D-arginine and D-NAME had no significant effect on rSNA. 5. The
      results indicate that endogenous nitric oxide in the lower thoracic spinal cord
      (1) has a potent excitatory action on renal sympathetic preganglionic neurones,
      and (2) helps to maintain the tonic activity of renal sympathetic nerves under
      resting conditions.

PMID- 7714832
TI  - Effect of hypoxia on force, intracellular pH and Ca2+ concentration in rat
      cerebral and mesenteric small arteries.
AB  - 1. The effect of severe hypoxia on force, intracellular Ca2+ concentration
      ([Ca2+]i) and pHi was studied in isolated small arteries from rat brain and rat
      mesenterium. The arteries were mounted for isometric force recording while
      [Ca2+]i was measured with fura-2 or pHi was measured with bis
      carboxyethylcarboxyfluorescein (BCECF). 2. Hypoxia reduced the force development
      in response to arginine vasopressin (AVP) while [Ca2+]i was unchanged or only
      slightly reduced. Inhibition of acid extrusion by omission of sodium caused no
      force development in mesenteric arteries, but the fall in pHi was enhanced during
      hypoxia. In cerebral arteries, hypoxia reduced the force development associated
      with omission of sodium, and the fall in pHi was less than during normoxic
      conditions. When acid extrusion was intact, pHi was not affected by hypoxia and
      the changes in pHi during activation with AVP were similar during hypoxia and in
      the control situation. 3. Although a decrease in smooth muscle [Ca2+]i may be
      partly responsible for the reduced force development during hypoxia, [Ca2+]i
      independent mechanism(s) may play an even more important role. Furthermore,
      although hypoxia and force development are associated with enhanced acid
      production, acid extrusion maintains pHi near the control level and it is
      unlikely that a decrease in smooth muscle pHi plays any role in the reduced force
      development during hypoxia.

PMID- 7714833
TI  - Involvement of endothelin-1 in hypoxic pulmonary vasoconstriction in the lamb.
AB  - 1. Using isolated pulmonary resistance vessels from mature fetal lamb and
      chronically instrumented lambs (8-17 days old), we have examined whether hypoxic
      pulmonary vasoconstriction is sustained by activation of a constrictor mechanism
      or suppression of a dilator mechanism. 2. Hypoxia contracted both arteries and
      veins in vitro, and the contraction was greater with the former. After removing
      the endothelium, arteries responded faster to hypoxia, but the magnitude of the
      response remained unchanged. 3. Hypoxic arteries, unlike normally oxygenated
      arteries, did not contract with either indomethacin (2.8 microM) or N omega-nitro
      L-arginine methyl ester (L-NAME, 100 microM). The same vessels relaxed with
      sodium nitroprusside (SNP, 0.001-10 microM) but not with bradykinin (0.1-100 nM).
      4. Endothelin-1 (ET-1, 0.01-10 nM) contracted isolated arteries and veins under
      normoxic and hypoxic conditions. In both vessels, the contraction was fast in
      onset and subsidence, and was inhibited by the ETA receptor antagonist BQ123 (1
      microM). The ET-1 precursor, big ET-1 (100 nM), also contracted arteries and
      veins, but compared with ET-1 its action was slower in development. Big ET-1
      contraction, unlike ET-1 contraction, was curtailed by the inhibitor of the ET-1
      converting enzyme, phosphoramidon (50 microM). 5. ET-1 (0.1-10 nM) had no effect
      on isolated arteries precontracted with a thromboxane A2 (TXA2) analogue (ONO
      11113) and treated with BQ123 (10 microM). Under the same conditions, ET-1
      relaxed the veins. Accordingly, in the absence of BQ123 treatment, the selective
      ETB receptor agonist IRL-1620 (0.1-100 nM) relaxed the contracted veins but not
      the arteries. 6. BQ123 (10 microM) inhibited the constriction of isolated
      arteries and veins to hypoxia. Likewise, in the conscious lamb a bolus of BQ123
      (0.4 mg kg-1, injected into the pulmonary artery) curtailed the rise in pulmonary
      vascular resistance (Rpa) brought about by alveolar hypoxia without changing
      significantly systemic vascular resistance (Rao). Under normoxia, Rpa was
      insignificantly affected by BQ123. 7. The results indicate that pulmonary
      resistance arteries are more susceptible to hypoxia than the veins, and that
      hypoxic vasoconstriction does not require an intact endothelium to occur. Hypoxic
      tone is ascribed primarily to intramural generation of ET-1, while removal of the
      tonic action of a relaxant may only have an accessory role in the response.

PMID- 7714834
TI  - Involvement of vasodilator mechanisms in arterial pressure lability after sino
      aortic baroreceptor denervation in rat.
AB  - 1. To examine the regional haemodynamic basis of arterial pressure lability seen
      after sino-aortic baroreceptor denervation (SAD), simultaneous beat-to-beat
      recordings of arterial pressure and indices of regional blood flows (Doppler
      probes around the subdiaphragmatic and lower abdominal aortae and the superior
      mesenteric artery) were performed in the same conscious rats (n = 7) before, 1
      and 14 days after SAD. 2. Acute SAD increased arterial pressure, decreased
      regional blood flows and vascular conductances, and potentiated the depressor and
      vasodilator effects of ganglionic blockade with trimethaphan, suggesting
      sympathetic overactivity. All parameters chronically returned to or near normal.
      3. Both acute and chronic SAD increased the variability of arterial pressure and
      of regional conductances. Arterial pressure lability was characterized by a
      mixture of depressor and pressor events which were associated with regional
      vasodilatations and vasoconstrictions, respectively. This haemodynamic pattern
      was not affected by acute beta-adrenoceptor blockade with propranolol. 4. In
      conscious rats, the baroreceptor reflex acts to buffer the spontaneous
      variability of regional vascular conductances and thereby stabilizes arterial
      pressure. Sino-aortic baroreceptor denervation-induced arterial pressure lability
      does not depend on the level of sympathetic activation, and is determined by the
      relative contribution of depressor and pressor events accompanied by extensive
      vasodilatations and vasoconstrictions, respectively. Vasodilatations are not
      caused by the stimulation of vascular beta 2-adrenoceptors.

PMID- 7714836
TI  - Post-spike facilitation of neck EMG by cat tectoreticulospinal neurones during
      orienting movements.
AB  - 1. The activity of fourteen tectoreticulospinal neurones (TRSNs) was recorded
      intraaxonally in the caudal pons of alert cats during orienting movements towards
      visual stimuli. TRSN spikes were used to compute the spike-triggered average
      (STA) of rectified EMG of dorsal neck muscles. 2. Eight TRSNs for which 400-2532
      spikes were available were analysed with the STA technique. When the STA was
      computed from all spikes, significant post-spike facilitation (PSF) was obtained
      for six of eighteen cell-muscle pairs investigated (5 TRSNs). The mean relative
      amplitude of PSFs was 7.4% (S.D. 3.7). The onset latencies ranged from 1.1 to 5.0
      ms and mean duration was 11.4 +/- 3.1 ms (mean +/- S.D.). 3. Interspike interval
      distributions were unimodal, with modes between 2.7 and 12.7 ms. Spike trains of
      TRSNs that produced significant PSFs contained 5-13% of the interspike intervals
      < or = 5 ms and 22-37% of the intervals < or = 10 ms. To evaluate the
      contribution of short intervals to PSF, STAs were computed separately for spikes
      preceded by 'short' (< or = 5 or < or = 10 ms) and 'long' (> 5 or > 10 ms)
      intervals. 4. When computed from spikes preceded by 'long' intervals, PSF
      amplitudes were small (mean +/- S.D., 5.3 +/- 2.7%) and onset latencies measured
      by cusum ranged between 2.4 and 5.4 ms. This is longer than the estimated minimal
      latency of monosynaptic facilitatory effect on neck EMG (1.9-2.1 ms). 5. Relative
      amplitudes of PSF obtained with spikes preceded by 'short' intervals were much
      larger (mean +/- S.D., 14.8 +/- 7.4%), but cusums indicated negative latencies
      for four of six PSFs. The unrealistically short onset latencies could be
      accounted for by the summation of facilitation from the trigger spike with that
      of the preceding spikes. In four of five TRSNs a large increase of PSF amplitude
      (from 3.2 to 7.2 times the amplitude obtained from 'long' intervals) suggests the
      presence of frequency-dependent potentiation of synaptic transmission. 6. This
      study unequivocally demonstrates that some TRSNs produce significant post-spike
      facilitation of neck motoneurones. This facilitation could be mediated by
      monosynaptic tectomotoneuronal connections although a contribution by disynaptic
      connections cannot be definitively ruled out. The high instantaneous firing rates
      of TRSNs produce a potentiation of the otherwise weak facilitatory action of
      TRSNs that presumably contributes to a rapid recruitment of motoneurones during
      initiation of head orienting movements.

PMID- 7714835
TI  - The genetic advantage hypothesis in cystic fibrosis heterozygotes: a murine
      study.
AB  - 1. The delta F508 mutation of the cystic fibrosis (CF) gene is of high frequency
      in man (1 in 25) and in homozygotes causes cystic fibrosis. It is suggested that
      cystic fibrosis heterozygotes withstand secretory diarrhoea better than normal
      individuals and so are genetically advantaged. This hypothesis has been examined
      by measuring electrogenic chloride secretion in gut epithelia of normal and
      heterozygous CF mice. 2. Chloride secretory responses of normal and heterozygous
      colonic epithelia to forskolin, vasoactive intestinal polypeptide (VIP),
      isoprenaline, cholera toxin, heat-stable enterotoxin (STa), guanylin, carbachol
      and lysylbradykinin were examined. No significant differences in responses of
      tissues of the two genotypes were found. 3. Responses of normal and heterozygous
      ileal epithelia to forskolin and glucose were investigated. Heterozygous tissues
      responded as well as normal tissues. 4. Frusemide (furosemide) caused virtually
      identical inhibition of the chloride secretory responses to forskolin in colonic
      epithelia of both genotypes. 5. No evidence to support the genetic advantage
      hypothesis in ileal or colonic epithelia of the null CF mouse has been found, at
      least for acute responses. If the hypothesis is true then either (a) other non
      cystic fibrosis transmembrane conductance regulator (non-CFTR) transport
      processes are involved, (b) prolonged exposure to secretagogues is required, or
      (c) delta F508 CFTR is responsible for the protective effect.

PMID- 7714839
TI  - Breast cancer and its treatment.

PMID- 7714838
TI  - The barrier defense: skin hydration as infection control.

PMID- 7714837
TI  - Recovery of power output and muscle metabolites following 30 s of maximal sprint
      cycling in man.
AB  - 1. The recovery of power output and muscle metabolites was examined following
      maximal sprint cycling exercise. Fourteen male subjects performed two 30 s cycle
      ergometer sprints separated by 1.5, 3 and 6 min of recovery, on three separate
      occasions. On a fourth occasion eight of the subjects performed only one 30 s
      sprint and muscle biopsies were obtained during recovery. 2. At the end of the 30
      s sprint phosphocreatine (PCr) and ATP contents were 19.7 +/- 1.2 and 70.5 +/-
      6.5% of the resting values (rest), respectively, while muscle lactate was 119.0
      +/- 4.6 mmol (kg dry wt)-1 and muscle pH was 6.72 +/- 0.06. During recovery, PCr
      increased rapidly to 65.0 +/- 2.8% of rest after 1.5 min, but reached only 85.5
      +/- 3.5% of rest after 6 min of recovery. At the same time ATP and muscle pH
      remained low (19.5 +/- 0.9 mmol (kg dry wt)-1 and 6.79 +/- 0.02, respectively).
      Modelling of the individual PCr resynthesis using a power function curve gave an
      average half-time for PCr resynthesis of 56.6 +/- 7.3 s. 3. Recovery of peak
      power output (PPO), peak pedal speed (maxSp) and mean power during the initial 6
      s (MPO6) of sprint 2 did not reach the control values after 6 min of rest, and
      occurred in parallel with the resynthesis of PCr, despite the low muscle pH. High
      correlations (r = 0.71-0.86; P < 0.05) were found between the percentage
      resynthesis of PCr and the percentage restoration of PPO, maxSp and MPO6 after
      1.5 and 3 min of recovery. No relationship was observed between muscle pH
      recovery and power output restoration during sprint 2 (P > 0.05). 4. These data
      suggest that PCr resynthesis after 30 s of maximal sprint exercise is slower than
      previously observed after dynamic exercise of longer duration, and PCr
      resynthesis is important for the recovery of power during repeated bouts of
      sprint exercise.

PMID- 7714840
TI  - Angiotensin II receptors and potassium channels: targets for new cardiovascular
      drugs.

PMID- 7714841
TI  - The ABC's of tracheostomy care.

PMID- 7714842
TI  - Health care reform what every LPN should know.

PMID- 7714843
TI  - Stand up against varicose veins.

PMID- 7714844
TI  - Sex role orientation and fear.
AB  - Data from previous studies suggest that women report higher levels of fear than
      men do and that individuals who identify with the feminine sex role report higher
      levels of fear than do individuals who identify with the masculine sex role
      (Carey, Dusek, & Spector, 1988; Dillon, Wolf, & Katz, 1985). The relationship
      between sex role orientation and fear was investigated further in the present
      study, using self-report and behavioral measures. The female participants
      reported significantly higher levels of fear than did the male participants.
      Individuals who identified with a feminine sex role reported significantly higher
      levels of fear than did individuals who identified with a masculine sex role.
      However, we found no significant difference in behavioral fear among the various
      sex-typed groups.

PMID- 7714845
TI  - Narcissism, self-esteem, and parental nurturance.
AB  - Self-reported narcissism, self-esteem, and perceptions of parents as nurturing
      were examined in a sample of 459 undergraduates. In zero-order and partial
      correlations, dimensions from the Narcissistic Personality Inventory displayed
      inter-relationships and linkages with self-esteem and parental nurturance that
      conformed with the hypothesis that indices of narcissism fall along a continuum
      of mental health. Partial correlations controlling for self-esteem also indicated
      that at least some data for the more adaptive aspects of narcissism were mediated
      by healthier self-functioning. These results support recent suggestions that
      narcissism must be conceptualized within frameworks that include healthy self
      esteem.

PMID- 7714846
TI  - Yalom's model. Applied to an outpatient better breathers group.
AB  - 1. The decision to use Yalom's model for outpatient group psychotherapy in the
      psychological treatment of chronic lung patients was based not only on the
      existential issues such clients face on a daily basis, but also on the theory of
      underlying personality characteristics. 2. Therapeutic interventions target six
      areas: encourage open communication; establish a therapeutic alliance among
      members; encourage exploration of alternative problem-solving skills/behaviors;
      increase self- and interpersonal understanding; encourage open expression of
      feelings; and develop more fulfilling interpersonal relationships within the
      group that could be generalized to relationships outside the group. 3. Hope is
      the most important factor in determining group survival. An implicit and
      underlying hope seems to be that if they could unburden themselves, they might be
      able to breathe better and live longer, healthier lives.

PMID- 7714848
TI  - Adult survivors of childhood sexual abuse: survivor's disclosure and nurse
      therapist's response.
AB  - Recent literature pertinent to adult survivors suggests that childhood sexual
      abuse is a serious problem, and that disclosure is on the rise. The aftereffects
      of childhood sexual abuse can cause dysfunction in various aspects of the
      survivor's physical and mental health. Understanding the traumagenic dynamics of
      childhood sexual abuse and its aftereffects provides direction for the nurse
      therapist during both the client's disclosure and intervention planning. This
      knowledge assists the therapist in promoting mental health and healing, as well
      as providing comfort for the therapist. The nurse therapist's reactions to the
      client's disclosure can affect the way the client feels about disclosure and the
      therapeutic relationship. If a negative message is conveyed to the survivor at
      the time of disclosure, the feelings of betrayal, stigmatization, and
      powerlessness that the survivor experienced as a child will be replicated. This
      can damage the therapeutic relationship and delay the healing process. When
      disclosure is received and acted upon in a sensitive, therapeutic manner, the
      survivor is empowered and can enter with the nurse therapist into an effective
      therapeutic alliance. Nurse therapists should gain awareness of the types of
      emotional responses that can be engendered in the health professional during
      disclosure. Awareness of these emotional reactions can lead to the identification
      of coping strategies useful to both the therapist and the adult survivor. Coping
      strategies useful to the therapist include maintaining adequate boundaries,
      understanding oneself and one's responses to sexual-abuse issues, utilizing
      ongoing consultation or supervision, and preventing burnout.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7714847
TI  - Child abuse: ethical and legal concerns for the nurse.
AB  - 1. Nurses, as well as many other types of professionals, are required by law to
      report any incidence or evidence of child abuse or neglect. The nurse or other
      professional is immune from liability after reporting an incidence of child
      abuse, but the nurse can be held civilly and criminally liable if he or she fails
      to make a report of suspected abuse. 2. Nurses are permitted, by law, to enter
      evidence and testify on behalf of the victim, especially if it is deemed to be
      too harmful or traumatic for the child to endure. 3. Nurses can aid greatly in
      the prosecutorial process by utilizing their relationship with the victim to ease
      the often-daunting pressure of the courtroom and the difficulty in dealing with
      and recounting the abusive incidents.

PMID- 7714849
TI  - Nursing assistance for families of patients.
AB  - With deinstitutionalization, families have become the primary caregivers of
      persons with mental illness. Mental health professionals and family members must
      work together to prevent damage to our most valuable resource, the family.
      Nurses, who often provide the most continuous care for seriously mentally ill
      persons, are in a unique position to reach out to families and provide the help
      that they need as primary caregivers. Let us not fail our patients or their
      families.

PMID- 7714850
TI  - The use of psychotropic drugs to treat anxiety in the elderly.
AB  - Great care in prescribing and monitoring psychotropic medications for elderly
      patients must be taken because of their increased sensitivity to toxic side
      effects; their decreased physical resiliency, as compared to younger patients;
      and the risk of dependency and withdrawal when taking psychotropic medication.
      Psychosocial and psychotherapeutic interventions should be administered
      concurrently if pharmacotherapy is needed. When psychotropic medication is called
      for, the agent of choice should be that which results in the least amount of
      autonomic nervous system toxicity and sedation. Short half-life benzodiazepines
      in low doses are generally the best options for elderly patients in need of
      psychotropic medication. Unlike benzodiazepines with longer half-lives, they
      cause no metabolite accumulation and have a lower potential for toxicity.

PMID- 7714851
TI  - Unity in diversity. Outcomes of the Geropsychiatric Nursing Survey.
AB  - The 264 persons who responded to the geropsychiatric nursing survey were diverse
      in both preparation and practice arenas. They remained up-to-date in the field
      through journals, certification and professional memberships, and they supported
      clinical geropsychiatric nursing research and the need to develop standards in
      geropsychiatric nursing education. Finally, these nurse respondents expressed a
      wide variety of policy, practice and educational concerns, most related to
      improved care for geropsychiatric patients and their families. Obviously,
      limitations exist to the generalizability of these survey results. First,
      respondents to this survey, which appeared in two journals, may not be
      representative of the overall geropsychiatric nursing population. Additionally,
      the methods for summarizing the survey results are not scientific. However, these
      results enable us to develop a picture of the geropsychiatric nursing community
      and provide a foundation for understanding the population and its
      characteristics.

PMID- 7714852
TI  - Article raises questions.

PMID- 7714853
TI  - Nurse and patient rights: can both be protected?

PMID- 7714855
TI  - Workplace mistreatment: its relationship to interpersonal violence.

PMID- 7714854
TI  - Psychosocial factors in HIV-infected men examined.

PMID- 7714856
TI  - Scheduled brief admissions: patient "tuneups".
AB  - 1. Incorporating brief, planned admissions into the treatment plan of chronically
      mentally disabled patients has demonstrated positive outcomes related to health
      care services, as well as to the patients' perceptions of their own health
      status. 2. A comparison of the "Tuneup" program before and since its inception
      showed that, while the number of patient hospitalizations increased, the
      patients' length of stay, amount of unplanned hospitalizations, and cost
      decreased significantly during this period. 3. The chronically mentally ill are a
      population at risk for a variety of hardships, including rehospitalization,
      social isolation, homelessness, and even death. Psychiatric nurses who understand
      the needs of these persons can serve as a vital force in mental health care
      reform.

PMID- 7714858
TI  - [The misleading blue tympanic membrane. Prolapse of the internal jugular vein].
AB  - The authors report a case of a jugular bulb dehiscence extending to the tympanic
      cavity. They alert that the finding of a blue mass in the middle ear should evok
      the possibility of a vascular variant or abnormalitie. High resolution CT is
      extremely helpful in the correct diagnosis by showing the subtle and
      characteristic bone changes.

PMID- 7714857
TI  - [Evaluation of the diagnostic value of a test. Main information indices].
AB  - Evaluating a new diagnostic test is an essential step required before using a new
      examination technique. The information concerning the disease provided by the
      test must be examined in terms of diagnostic value and cost. A test can be
      evaluated using several indexes. For tests giving binary results, the main
      information indexes were defined and the calculation of the index was illustrated
      by an example. The sensitivity, specificity, the Youden index, and the positive
      and negative predictive values were presented together with the likelihood and
      odds-ratio. For tests giving quantitative results, the analysis of the ROC curves
      was discussed. Indexes were interpreted in terms of disease prevalence, the
      modalities (diagnosis, screening) for applying the test, the sampling technique
      for the tested population, the gain in diagnosis, and cost of the examination.

PMID- 7714859
TI  - [Imaging protocol in diseases of the naso-sinusal cavities].

PMID- 7714860
TI  - [Blunt injury of the larynx by hanging. X-ray computed tomographic aspect].
AB  - The closed laryngeal traumas by attempt of hanging are rarely studied by medical
      imaging. The lesions are evaluated by fiberoptic endoscopy and CT scan. We report
      a case of complicated lesions of the larynx with rupture of the cricothyroid
      membrane, diagnosed by CT scan and we discuss the usefulness of this technique.

PMID- 7714861
TI  - [MRI of the operated lumbar spine and enhancement of intradural nerve roots. 478
      cases].
AB  - Authors report a study of 478 MR imaging in failed back surgery syndrome.
      Enhancing nerve roots were detected in 73.8%, with a significant higher
      percentage in male patients, and long postoperative delay. There was no
      significant correlation with age, enhancement of epidural scar (epidural scar was
      seen in 75.7%) and disk herniation (seen in 25.9%). Alteration of blood-nerve
      barrier causes enhancement, but the mecanism is nuclear: mechanical, biological,
      immunological or Wallerian degeneration. Diagnostic and prognostic value of
      enhancement are not proven and a study of asymptomatic patients is necessary.

PMID- 7714862
TI  - [Intracranial pneumatocele secondary to fronto-ethmoidal osteoma. Apropos of a
      case].
AB  - The authors report a case of spontaneous pneumatocele consecutive fronto
      ethmoidal osteoma which was unrecognized until its complication. This cases
      illustrated the interest of the CT scan for the topographie diagnostic of the
      pneumatocele and the visualization of the osteomeduremerienne breache.

PMID- 7714863
TI  - [Neurocysticercosis disclosed by cerebrovascular complication].
AB  - Cysticercosis in one of the most common parasitoses in the world but is rare in
      France. This is the case of a thirty two years old man who had a stroke which
      revealed a neurocysticercosis, the diagnosis of which appeared on CT-scan. MR
      imaging gave a more precise topographical diagnosis of the cysticercosis lesions
      and allowed a physiopathological understanding of the stroke. The ischemic lesion
      in the lenticulostriate territory was due to cysts in the sylvian fissure at the
      level of the beginning of those arteries with a perilesional inflammatory
      reaction. We learned the link between cysticercosis and stroke studing the cases
      reported in the literature.

PMID- 7714864
TI  - [Rhabdomyolysis and truncular sciatica. 2 cases studied by MRI].
AB  - We report two cases of acute rhabdomyolysis in pelvic girdle muscles with sciatic
      palsy secondary to compression of the sciatic nerve trunk, with clinical and MRI
      correlation. The diagnosis of rhabdomyolysis is based on clinical and biological
      data, but diagnosis of compression complications secondary to swelling of the
      muscles, especially the compression of nerve trunk, is done by imaging. T2
      weighted images give a definite anatomical evaluation. They show enlarged high
      signal intensity muscles and anatomic relationship with the sciatic nerve from
      its emergence out of pelvis, giving a good correlation between rhabdomyolysis and
      the compressed nervous trunk. It helps for planning a possible surgical
      fasciotomy. However, MRI provides only morphological informations, but not
      differentiates edema from necrosis in involved muscles.

PMID- 7714866
TI  - [Colonic cystic pneumatosis. A specific x-ray computed tomographic diagnosis:
      apropos of 2 cases].

PMID- 7714865
TI  - [Percutaneous treatment of abdominal collections. Apropos of 135 cases].
AB  - The authors reviewed 135 abdominal collections, collected at the Radiologic
      Central Service over four years. The average age of the patients was 40 years.
      The abscesses sit especially in the liver (54 cases) and the psoas muscle (43
      cases). The percutaneous management was guided by ultrasonography in all the
      cases. The results were successful in 74%. Only 15 cases needed surgical therapy.
      The literature results are similar. The authors underline the percutaneous
      treatment interests, its efficacy, its complications and their therapy.

PMID- 7714867
TI  - [Colonic angiodysplasia. Rare cause of low digestive hemorrhage in young
      patients].
AB  - We report the following observation of a diffuse kind of colic angiodysplasia in
      a young subject. Usually to be find in old subjects and regarded as been
      degenerative origine, angiodysplasiae have been reported in young subjects and we
      are led to ponder over their nature. The contribution of diagnostic and
      therapeutic means and their respected place have been specified. In particular
      the significance of vascular radiology and the angiographic signs of this
      arterioveinous malformation have been developed.

PMID- 7714868
TI  - [Endovascular treatment of peripheral arteriovenous malformations].
AB  - The progress made by noninvasive exploration for the assessment of vascular
      malformations now allows the therapeutic strategies to be better established.
      While observation and conservative methods are most often chosen, some
      arteriovenous malformations lead to contemplating a palliative or curative
      treatment. In these cases, embolization currently plays a great role, associated
      or not to surgery. This embolization obviously can be contemplated only after a
      collegial decision to treat these malformations has been made, knowing that they
      may be silent or acquire an uncontrollable evolution potential. The authors
      present 3 cases of peripheral arteriovenous malformations, treated by an
      endovascular way, and remind the principles and indications of these
      embolizations.

PMID- 7714869
TI  - [Superior caval syndrome caused by chronic mediastinitis in Behcet's disease].
AB  - We report a case of Behcet disease complicated by superior vena cava syndrome
      secondary to extrinsic compression by mediastinal fibrosis. This association is
      not reported in literature. The habituel etiology of vena cava syndrome in Behcet
      disease is venous thrombosis. Radiological investigations of this syndrome are
      necessary to avoid an useless anticoagulant therapy.

PMID- 7714870
TI  - [A case of cystic lesion of aneurysmal type on a metatarsus].

PMID- 7714871
TI  - [Scientific societies. Scientific congresses. Radiological education.
      Telemedicine].

PMID- 7714873
TI  - The effect of delayed repair on microvascular patency rates.
AB  - The effect of delayed microsurgical arterial anastomosis on the patency rate in
      the rat femoral artery was evaluated. Sixteen Sprague-Dawley rats underwent
      ligation and repair of the right femoral arteries and repair of the left artery
      as a control. The rats were divided into four groups, and their right arteries
      were ligated for 24, 48, 72, or 96 hr. Patency was evaluated by the standard
      stripping test and flow after transection of the vessel. At 5 days after the
      arterial anastomosis, four of 16 arteries remained patent, two of which were in
      the 24-hr group. Histologic analysis revealed progressive damage to the arterial
      intima and media, as the time to repair was delayed. Delayed microsurgical
      arterial repairs of greater than 24 hr showed a poor patency rate, due to
      irreversible changes that occurred in the arterial intima and media.

PMID- 7714874
TI  - Anatomy and clinical applications of a composite cutaneo-subcutaneous flap based
      on the lateral superior genicular vessels.
AB  - A cutaneo-subcutaneous flap based on the lateral superior genicular artery was
      anatomically investigated and applied in three clinical cases. Consistent
      anatomy, a long vascular pedicle, fairly easy dissection, primary donor closure,
      and minimal donor-site morbidity are the most important advantages when a medium
      sized flap is needed. The flap may be used as a thin, delicate, free cutaneous
      subcutaneous transfer for reconstruction of skin defects. It may also be applied
      as an axial flap to cover defects of the popliteal region.

PMID- 7714872
TI  - [MRI of the internal auditory meatus. Is injection of gadolinium indispensable?].
AB  - OBJECT: To compare prospectively high resolution fast spin echo T2 weighted (FSE
      T2W) images and gadolinium-enhanced spin echo T1 weighted images for diagnosis of
      pathology of the internal auditory meatus (IAM). PATIENTS AND METHODS: 114
      patients underwent MR imaging at 1.5 T with the following protocol: axial images;
      whole brain FSE-T2W sequence (256 matrix); 2 sequences focused on IAM with high
      resolution FSE-T2W acquisitions (512 matrix, 3 mm sections with 1.5 mm
      overlapping); pre and postcontrast T1 weighted sequences focused on IAM.
      Examinations were viewed by senior neuroradiologists. RESULTS: 31 lesions were
      detected in the IAM by high resolution FSE-T2W images; 25 lesions were found in
      the IAM by postcontrast T1 weighted images, i.e. 6 false-positive results and
      none false-negative. On the basis of 228 studied IAMs the sensitivity,
      specificity and negative predictive value of this high resolution FSE-T2W
      sequence were 100%, 97% and 100% respectively. CONCLUSION: Gadolinium enhanced
      sequence is not indispensable if high resolution FSE-T2W images are normal.
      Gadolinium-enhanced sequence remains essential in others equivocal cases
      (difficult diagnosis or abnormal IAM).

PMID- 7714875
TI  - Vein conduits with interposition of nerve tissue for peripheral nerve defects.
AB  - Vein conduits with interposition of autogenous nerve tissue were used in 16
      peripheral nerves to reconstruct defects of between 2.0 and 5.8 cm. This
      technique was applied in nine digital nerves, four ulnar nerves, two median
      nerves, and one radial sensory nerve. A single vein conduit was used in digital
      nerve defects and two or three vein segments were used in defects of nerve
      trunks. Nerve tissue was sectioned from the proximal nerve stump and inserted
      inside the vein conduits. Follow-up of 2.5 to 3.5 years has revealed motor
      recovery to M4 in three nerves, M3+ in three, M2 in one nerve, and sensory
      recovery to S4 in two nerves, S3+ in five, S3 in four, S2+ in three and S0 in two
      nerves. Signs of muscle reinnervation of the repaired nerves were noted on
      electromyography. Two digital nerves with defects of over 5.0 cm did not show any
      signs of sensory recovery. Sectioning and placement of autogenous nerve tissue is
      thought to create fresh and additional sources for the release of neurotropic
      factors, and may serve to convey the neurotropic effect over a longer distance.
      This clinical study suggests that vein conduits with the interposition of nerve
      tissue is a practical and reliable procedure for nerve defects between 2.0 cm and
      4.5 cm.

PMID- 7714876
TI  - Functional evaluation of peripheral-nerve repair and the effect of hyperbaric
      oxygen.
AB  - The effect of hyperbaric oxygen (HBO) on peripheral-nerve recovery following
      devascularization and repair was studied, using the rat sciatic-nerve model. The
      right sciatic nerve was mobilized, stripped of the extrinsic blood supply,
      transected, and repaired in an epineurial fashion, using microsurgical technique.
      Following repair, animals were randomized into one of two groups: 1) control--no
      HBO (n = 20); 2) HBO treatment--twice daily for one week (1.75 hr dives, 100
      percent O2, 2.5 ATA) (n = 16). Nerve recovery was assessed weekly (total of 10
      weeks) by walking-track analysis, from which the sciatic function index (SFI) was
      calculated for each animal. Mean SFI scores were improved in the HBO-treatment
      group over controls, becoming statistically significant at weeks 7 through 10.
      These results suggest that functional recovery in transected, devascularized,
      peripheral nerves may be improved by 1 week of HBO treatment following
      microsurgical repair.

PMID- 7714877
TI  - Prosthetic vascular graft and autogenous vein graft with free-tissue transfer in
      attempted lower-limb salvage.
AB  - Chronic wounds of the lower extremity are frequent causes of osteomyelitis and
      amputation in patients with peripheral vascular disease. Advances in vascular
      surgical techniques, allowing distal arterial bypass via synthetic grafts or
      autogenous vein grafts, have significantly increased the frequency of limb
      salvage. In the last two decades, this increasing success has contributed to an
      even greater rate of extremity salvage. The authors report a case of attempted
      limb preservation, using a combination of macrovascular polytetrafluoroethylene
      (Goretex) grafting, reverse saphenous vein interposition, and vein-patch
      angioplasty, to facilitate microvascular free-tissue transfer.

PMID- 7714878
TI  - Scanning electron microscopy of microarterial anastomoses with a diode laser:
      comparison with conventional manual suture.
AB  - A diode-laser (830 nm)-assisted carotid artery end-to-end microanastomosis (LAMA)
      and a contralateral manual suture anastomosis (CMA) were performed in 70 Wistar
      rats. The vessel sealing was performed on the left carotid by laser pulses
      (average 3) of 500 mW power and 4.5 sec exposure time, the beam being focused on
      a spot of 300 microns diameter (700 W/cm2). The CMA was achieved on the right
      carotid by six 10-0 stitches. From day 0 to day 210, 40 specimens underwent
      scanning electron microscopy. The laser impact produced a wall injury of 100
      microns in width, with an immediate sealing effect due to protein denaturation
      and collagen fusion of media and adventitia. The anastomosis became re
      endothelialized by day 3, while the longitudinal arrangement of the endothelial
      cells was restored from day 10 on. In the long term, a thick collagenous meshwork
      of collagen and elastic fibers maintained the strength of the media, while normal
      endothelium covered the anastomosis. Inversely, after CMA vessel repair was
      delayed, and the anastomotic line was more irregular and underlined by medial
      fibrotic scar. In both anastomoses, the patency rate was 93 percent, with
      nonlethal complications. The advantages of LAMA vs. CMA were: shorter operating
      time (13 min/22 min), reduced intraoperative trauma, better healing of
      endothelium, and a miniaturization of the laser source well adapted to
      microsurgery.

PMID- 7714879
TI  - Large amounts of polylactic acid in contact with divided nerve sheaths have no
      adverse effects on regeneration.
AB  - The stumps of divided rat sciatic nerves were coapted by suturing the epineurium
      to a small rectangular device made of a sheet of polylactic acid. One month
      later, significant degradation of the implanted material was observed. At that
      time, the local condition of the nerve was excellent, and the precise location of
      the initial injury could not be determined by examination under the operating
      microscope. Histology confirmed that there was no visible reaction to the
      biodegradable substance or its metabolites, and that neurotization of the distal
      stump was satisfactory. These findings were in agreement with those of other
      studies, and indicated that polylactic-acid devices affixed to divided nerves
      have no adverse effect on regeneration.

PMID- 7714880
TI  - Mechanical leech therapy to relieve venous congestion.
AB  - When faced with venous insufficiency following replantation or free-tissue
      transfer, the surgeons' first choice is surgical repair. When repair is not
      possible, medicinal leeches may be applied to relieve congestion. However,
      leeches increase the possibility of infection through their gut contents, and
      there are times when the available leech supply is short and the need for rapid
      exsanguination is great. A mechanical device has been developed and tested which
      could be used as a substitute for the medicinal leech. Using a venous-congested
      rat epigastric flap, this device was demonstrated to be superior to a medicinal
      leech in restoring capillary perfusion to the flap during the first hour of
      exsanguination. The device may offer an alternative to the medicinal leech for
      the clinical treatment of small areas of tissue with venous congestion.

PMID- 7714881
TI  - Perioperative fluid management in microvascular surgery.
AB  - The aim of intravenous fluid therapy in microvascular surgery is to maintain
      intravascular fluid volume for optimal tissue blood flow and oxygen transport to
      all tissues, including the free transferred tissue. General problems include the
      prolonged surgical procedures, frequently resulting in hypothermia and peripheral
      vasoconstriction, which may affect blood flow to the transplanted tissue. The
      surgical wounds may also be extensive, and can cause profound and sometimes
      underestimated fluid and blood loss. The choice of fluids is important, since
      free flaps and replants are at increased risk of developing edema, due to lack of
      lymphatic drainage and a decreased ability to reabsorb excessive interstitial
      fluid. Therefore, it is suggested that crystalloids be used only for insensible
      fluid loss, but that synthetic colloids (preferably pentastarch) be used for the
      replacement of plasma constituents. Hypertonic saline may have beneficial effects
      in ischemic and edematous flaps and replants. To optimize blood flow to the free
      flap, it is advisable to use moderate hemodilution. This facilitates the
      maintenance of high cardiac output and low peripheral vascular resistance. In
      addition, body temperature should be kept as close to normal as possible and,
      after completion of the microvascular anastomosis, arterial blood pressure should
      be kept near normal, to insure adequate perfusion pressure.

PMID- 7714882
TI  - Microcirculatory response to surgical trauma in composite-tissue transfer.
AB  - A rat cremaster muscle-flap model for direct in vivo microcirculatory studies was
      combined with a rat hind-limb amputation/replantation model, to evaluate changes
      related to transfer trauma. Forty-eight inbred Sprague-Dawley rats were studied
      in two experimental groups. In a control group, the cremaster muscle was
      dissected as an island tube flap, transposed into the hind limb, and anchored at
      ankle level. No amputation was performed. In a second composite-limb-cremaster
      graft group, the limb, with the inserted cremaster muscle flap, was amputated at
      mid-thigh level, and transferred to a recipient animal. In both groups, at follow
      up periods of 1, 24, 48, and 72 hr, the cremaster flap was withdrawn from the
      limb and prepared for microcirculatory studies. The following parameters were
      measured: vessel diameters, RBC velocities, capillary density, and leukocytes in
      the postcapillary venules. Arteriolar and venular diameters, as well as RBC
      velocity values, were comparable in both groups. However, the composite isografts
      presented 50 percent more leukocytes sticking to the lumen of the postcapillary
      venules (p < 0.05) immediately following transfer. In addition, a significant
      decrease (12 percent) in the number of perfused capillaries was observed in the
      composite grafts throughout 72 hr. In this study on composite tissue transfer,
      trauma alone compromised the microcirculatory integrity of the tissue and proved
      to act as an independent factor. This should be considered during
      allotransplantations, where the addition of a rejection factor can further
      compromise graft survival.

PMID- 7714883
TI  - Review article of rat muscle and myocutaneous flap models.

PMID- 7714885
TI  - Transport and dynamics of molecules dissolved in maize root cortex membranes.
AB  - Translational diffusion of a fluorescent sterol probe was measured in the plasma
      membranes of protoplasts isolated from cortical cells of the primary root of
      maize seedlings. The apparent lateral diffusion coefficient was typically
      observed to be nearly insensitive to temperature, while the mobile fraction
      increased with increasing temperature. These fluorescence photobleaching recovery
      (FPR) measurements were compared with the electron paramagnetic resonance (EPR)
      spectra of the methyl ester of 13-doxyl palmitic acid in membranes of corn root
      tissue in situ. The complex spectra observed with this probe were analyzed as
      weighted sums of simpler spectra of various order parameters and rotational
      correlation times. The reconstituted spectra calculated from the model show that
      EPR also detects a mobile (less ordered, fluid) fraction, distinguished by the
      order parameter S = 0.1 to 0.2, which becomes more abundant as temperature
      increases and is qualitatively comparable to the mobile fraction determined by
      the FPR method. The observed results on the mobile fractions and the diffusion
      rates for translational (FPR) as well as rotational (EPR) motions are interpreted
      in terms of membrane organization, thus providing information on the population
      and structural patterns of the coexisting domains with a special emphasis on the
      response of the membrane to temperature changes.

PMID- 7714887
TI  - The K+ channel in the plasma membrane of rye roots has a multiple ion residency
      pore.
AB  - The permeation of K+ and Na+ through the pore of a K+ channel from the plasma
      membrane of rye roots was studied in planar 1-palmitoyl-2-oleoyl
      phosphatidylethanolamine bilayers. The pore contains at least two ion-binding
      sites which can be occupied simultaneously. This was indicated by: (i) biphasic
      relationships with increasing cation concentration of both channel conductance at
      the zero-current (reversal) potential of the channel (Erev) and unitary-current
      at a specified voltage and (ii) a decline in Erev in the presence of equimolar
      Na+ (cis):K+ (trans) as the cation concentration was increased. To determine the
      spatial characteristics and energy profiles for K+ and Na+ permeation, unitary
      current/voltage data for the channel were fitted to a three energy-barrier, two
      ion-binding site (3B2S) model. The model allowed for simultaneous occupancy of
      binding sites and ionic repulsion within the pore, as well as surface potential
      effects. Results suggested that energy peaks and energy wells (ion binding sites)
      were situated asymmetrically within the electrical distance of the pore, the
      trans energy-well being closer to the center of the pore than its cis
      counterpart; that the energy profile for K+ permeation differed significantly
      from that of Na+ in having a higher cis energy peak and a deeper cis energy well;
      that cations repelled each other within the pore and that vestibule surface
      charge was negligible. The model successfully simulated various aspects of K+ and
      Na+ permeation including: (i) the complexities in current rectification of a wide
      range of contrasting ionic conditions; (ii) the biphasic relationships with
      increasing cation concentration of both channel conductance at Erev and unitary
      current at a specified voltage; (iii) the decline in Erev in equimolar Na+
      (cis):K+ (trans) as cation concentrations were increased and (iv) the complex
      relationships between mole fraction and Erev at total cation concentrations of
      100 and 300 mM.

PMID- 7714886
TI  - Evidence for coupling between Na+ pump activity and TEA-sensitive K+ currents in
      Xenopus laevis oocytes.
AB  - Using the two-microelectrode voltage clamp technique in Xenopus laevis oocytes,
      we estimated Na(+)-K(+)-ATPase activity from the dihydroouabain-sensitive current
      (IDHO) in the presence of increasing concentrations of tetraethylammonium (TEA+;
      0, 5, 10, 20, 40 mM), a well-known blocker of K+ channels. The effects of TEA+ on
      the total oocyte currents could be separated into two distinct parts: generation
      of a nonsaturating inward current increasing with negative membrane potentials
      (VM) and a saturable inhibitory component affecting an outward current easily
      detectable at positive VM. The nonsaturating component appears to be a barium
      sensitive electrodiffusion of TEA+ which can be described by the Goldman-Hodgkin
      Katz equation, while the saturating component is consistent with the expected
      blocking effect of TEA+ on K+ channels. Interestingly, this latter component
      disappears when the Na(+)-K(+)-ATPase is inhibited by 10 microM DHO. Conversely,
      TEA+ inhibits a component of IDHO with a KD of 25 +/- 4 mM at +50 mV. As the
      TEA(+)-sensitive current present in IDHO reversed at -75 mV, we hypothesized that
      it could come from an inhibition of K+ channels whose activity varies in parallel
      with the Na(+)-K(+)-ATPase activity. Supporting this hypothesis, the inward
      portion of this TEA(+)-sensitive current can be completely abolished by the
      addition of 1 mM Ba2+ to the bath. This study suggests that, in X. laevis
      oocytes, a close link exists between the Na-K-ATPase activity and TEA(+)
      sensitive K+ currents and indicates that, in the absence of effective K+ channel
      inhibitors, IDHO does not exclusively represent the Na(+)-K(+)-ATPase-generated
      current.

PMID- 7714884
TI  - Structure and function of amiloride-sensitive Na+ channels.
AB  - A new molecular biological epoch in amiloride-sensitive Na+ channel physiology
      has begun. With the application of these new techniques, undoubtedly a plethora
      of new information and new questions will be forthcoming. First and foremost,
      however, is the question of how many discrete amiloride-sensitive Na+ channels
      exist. This question is important not only for elucidating structure-function
      relationships, but also for developing strategies for pharmacological or,
      ultimately, genetic intervention in such diseases as obstructive nephropathy,
      Liddle's syndrome, or salt-sensitive hypertension where amiloride-sensitive Na+
      channel dysfunction has been implicated [17, 62]. Epithelia Na+ channels purified
      from kidney are multimeric. However, it is not yet clear which subunits are
      regulatory and which participate directly as a part of the Na+ conducting core
      and what is the nature of the gate. The combination of electrophysiologic
      techniques such as patch clamp and the ability to study reconstituted channels in
      planar lipid bilayers along with molecular biology techniques to potentially
      manipulate the individual subunits should provide the answers to questions that
      have puzzled physiologists for decades. It seems clear that the robust
      versatility of the channel in responding to a wide range of differing and
      potentially synergistic regulatory inputs must be a function of its multimeric
      structure and relation to the cytoskeleton. Multiple mechanisms of regulation
      imply multiple regulatory sites. This hypothesis has been validated by the
      demonstration that enzymatic carboxyl methylation and phosphorylation have both
      individual and synergistic effects on the purified channel in planar lipid
      bilayers. Of the multiple mechanisms proposed for channel regulation, evidence is
      now available to support the ideas that channels may be activated (or
      inactivated) by direct modifications including phosphorylation and carboxyl
      methylation, by activation or association of regulatory proteins such as G
      proteins, and by recruitment from subapical membrane domains. The observation
      that channel gating is achieved primarily through regulation of open probability
      without alterations in conductance may simplify future understanding of the
      molecular events involved in gating once the regulatory sites have been
      identified. As more Na+ channels or Na+ channel subunits are cloned from
      different epithelia, it will become possible to piece together the puzzle of
      epithelial Na+ channels. It is interesting to observe that renal Na+ channel
      proteins contain a subunit which falls into the 70 kD range. This size protein is
      in the range reported for the aldosterone-induced proteins [12, 46,
      153].(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714889
TI  - Single-microelectrode voltage clamp measurements of pancreatic beta-cell membrane
      ionic currents in situ.
AB  - A conventional patch clamp amplifier was used to test the feasibility of
      measuring whole-cell ionic currents under voltage clamp conditions from beta
      cells in intact mouse islets of Langerhans perifused with bicarbonate Krebs
      buffer at 37 degrees C. Cells impaled with a high resistance microelectrode (ca.
      0.150 G omega) were identified as beta-cells by the characteristic burst pattern
      of electrical activity induced by 11 mM glucose. Voltage-dependent outward K+
      currents were enhanced by glucose both in the presence and absence of
      physiological bicarbonate buffer and also by bicarbonate regardless of the
      presence or absence of glucose. For comparison with the usual patch clamp
      protocol, similar measurements were made from single rat beta-cells at room
      temperature; glucose did not enhance the outward currents in these cells. Voltage
      dependent inward currents were recorded in the presence of tetraethylammonium
      (TEA), an effective blocker of the K+ channels known to be present in the beta
      cell membrane. Inward currents exhibited a fast component with activation
      inactivation kinetics and a delayed component with a rather slow inactivation;
      inward currents were dependent on Ca2+ in the extracellular solution. These
      results suggest the presence of either two types of voltage-gated Ca2+ channels
      or a single type with fast and slow inactivation. We conclude that it is feasible
      to use a single intracellular microelectrode to measure voltage-gated membrane
      currents in the beta-cell within the intact islet at 37 degrees C, under
      conditions that support normal glucose-induced insulin secretion and that glucose
      enhances an as yet unidentified voltage-dependent outward K+ current.

PMID- 7714891
TI  - Automated correction of linear deformation due to sectioning in serial
      micrographs.
AB  - This paper describes an objective and automatic method for detection and
      correction of sectioning deformations in digitized micrographs, as well as an
      evaluation of the method applied to light and electron microscopic images of semi
      thin and ultra-thin serial sections from brain cortex. The detection is based on
      matching of image subregions and the deformation model is bi-linear, i.e. two
      first-order polynomials are used for modelling compression/expansion in
      perpendicular directions. The procedure is applicable to prealigned serial two
      dimensional sections and is primarily aimed at three-dimensional reconstruction
      of tissue samples consisting of a large number of cells with random distribution
      and morphology.

PMID- 7714888
TI  - Attenuation of channel kinetics and conductance by cholesterol: an interpretation
      using structural stress as a unifying concept.
AB  - The ubiquity of cholesterol in cell membranes and changes in its concentration
      during development, aging and in various diseases suggest that it plays an
      important role in modulating cell function. We examined this possibility by
      monitoring the effects of cholesterol on the activity of the calcium-activated
      potassium (BK) channel reconstituted into lipid bilayers from rat brain
      homogenates. Increasing the cholesterol concentration to 11% of total lipid
      weight resulted in a 70% reduction in channel mean open time and a reduction of
      the open probability of the channel by 80%. Channel conductance was reduced by
      7%. Cholesterol is known to change the order state and the modulus of
      compressibility of bilayers. These physico-chemical changes may be translated
      into an overall increase in the structural stress in the bilayer, and this force
      may be transmitted to proteins residing therein. By examining the characteristics
      of the BK channel as a function of temperature, in the presence and absence of
      cholesterol, we were able to estimate the activation energy based on Arrhenius
      plots of channel kinetics. Cholesterol reduced the activation energy of the BK
      channel by 50% for the open to closed transition. This result is consistent with
      an increased stress energy in the bilayer and favors the channel moving into the
      closed state. Taken together, these data are consistent with a model in which
      cholesterol induces structural stress which enhances the transition from the open
      to the closed state of the channel. We suggest that this is an important
      mechanism for regulating the activity of membrane-integral proteins and therefore
      membrane function, and that the concept of structural stress may be relevant to
      understanding the modulation of ion channel activity in cell membranes.

PMID- 7714890
TI  - Estimating and eliminating junctional current in coupled cell populations by leak
      subtraction. A computational study.
AB  - The quantitative characterization of ion channel properties in pancreatic beta
      cells under typical patch clamp conditions can be questioned because of the
      unreconciled differences in experimental conditions and observed behavior between
      microelectrode recordings of membrane potential in intact islets of Langerhans
      and patch recordings of single cells. Complex bursting is reliably observed in
      islets but not in isolated cells under patch clamp conditions. E. Rojas et al.
      (J. Membrane Biol. 143:65-77, 1995) have attempted to circumvent these
      incompatibilities by measuring currents in beta-cells in intact islets by voltage
      clamping with intracellular microelectrodes (150-250 M omega tip resistance). The
      major potential pitfall is that beta-cells within the islet are electrically
      coupled, and contaminating coupling currents must be subtracted from current
      measurements, just as linear leak currents are typically subtracted. To
      characterize the conditions under which such coupling current subtraction is
      valid, we have conducted a computational study of a model islet. Assuming that
      the impaled cell is well clamped, we calculate the native and coupling components
      of the observed current. Our simulations illustrate that coupling can be reliably
      subtracted when neighbor cells' potentials are constant or vary only slowly
      (e.g., during their silent phases) but not when they vary rapidly (e.g., during
      their active phases). We also show how to estimate coupling conductances in the
      intact islet from measurements of coupling currents.

PMID- 7714892
TI  - Application of confocal laser microscopy and three-dimensional Voronoi diagrams
      for volume and surface estimates of interphase chromosomes.
AB  - This study demonstrates the use of Voronoi tessellation procedures to obtain
      quantitative morphological data for chromosome territories in the cell nucleus.
      As a model system, chromosomes 7 and X were visualized in human female amniotic
      fluid cell nuclei by chromosomal in situ suppression hybridization with
      chromosome-specific composite probes. Light optical serial sections of 18 nuclei
      were obtained with a confocal scanning laser fluorescence microscope. A three
      dimensional (3-D) tessellation of the image volumes defined by the stack of
      serial sections was then performed. For this purpose a Voronoi diagram, which
      consists of convex polyhedra structured in a graph environment, was built for
      each nucleus. The chromosome territories were extracted by applying the Delaunay
      graph, the dual of the Voronoi diagram, which describes the neighbourhood in the
      Voronoi diagram. The chromosome territories were then described by three
      morphological parameters, i.e. volume, surface area and a roundness factor (shape
      factor). The complete evaluation of a nucleus, including the calculation of the
      Voronoi diagram, 3-D visualization of extracted territories using computer
      graphic methods and parameterization was carried out on a Silicon Graphics
      workstation and was generally completed within 5 min. The geometric information
      obtained by this procedure revealed that both X- and 7-chromosome territories
      were similar in volume. Roundness factors indicated a pronounced variability in
      interphase shape for both pairs of chromosomes. Surface estimates showed a
      significant difference between the two X-territories but not between chromosome 7
      territories.

PMID- 7714893
TI  - PHOEBE, a prototype scanning laser-feedback microscope for imaging biological
      cells in aqueous media.
AB  - Based on the principle of laser-feedback interferometry (LFI), a laser-feedback
      microscope (LFM) has been constructed capable of providing an axial (z)
      resolution of a target surface topography of approximately 1 nm and a lateral
      (x,y) resolution of approximately 200 nm when used with a high-numerical-aperture
      oil-immersion microscope objective. LFI is a form of interferometry in which a
      laser's intensity is modulated by light re-entering the illuminating laser.
      Interfering with the light circulating in the laser resonant cavity, this back
      reflected light gives information about an object's position and reflectivity.
      Using a 1-mW He-Ne (lambda = 632.8 nm) laser, this microscope (PHOEBE) is capable
      of obtaining 256 x 256-pixel images over fields from (10 microns x 10 microns) to
      (120 microns x 120 microns) in approximately 30 s. An electromechanical feedback
      circuit holds the optical pathlength between the laser output mirror and a point
      on the scanned object constant; this allows two types of images (surface
      topography and surface reflectivity) to be obtained simultaneously. For
      biological cells, imaging can be accomplished using back-reflected light
      originating from small refractive-index changes (> 0.02) at cell membrane/water
      interfaces; alternatively, the optical pathlength through the cell interior can
      be measured point-by-point by growing or placing a cell suspension on a higher
      reflecting substrate (glass or a silicon wafer).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714894
TI  - Exclusive expression of C. elegans osm-3 kinesin gene in chemosensory neurons
      open to the external environment.
AB  - In Caenorhabditis elegans three genetic loci osm-3, unc-104 and unc-116 have been
      identified, which encode anterograde motor kinesin. Here we show that osm-3
      encodes a 672 amino acid long kinesin-like protein (KLP) that contains all three
      functional domains similar to the kinesin heavy chain, including a globular motor
      region, an alpha-helical coiled-coil rod, and a globular tail region. OSM-3 shows
      homology in both the motor and rod domains with kinesins from divergent species
      such as mouse KIF3, and sea urchin KRP95, and also with the rod domains of
      several non-kinesin proteins, such as myosin, ezrin, outer membrane proteins
      alpha precursor OMPA, yeast intracellular protein transport USO1, and the rat
      neurofilament NF-H. Temporal and spatial expression of the osm-3::lacZ fusion
      gene during development is limited to an exclusive set of 26 chemosensory neurons
      whose dendritic endings are exposed to the external environment, including six
      IL2 neurons of the inner labial sensilla, eight pairs of amphid neurons (ADF,
      ADL, ASE, ASG, ASH, ASI, ASJ, ASK) in the head, and two pairs of phasmid neurons
      (PHA and PHB) in the tail. Our data are consistent with the known structural
      defects in the amphid and phasmid sensilla in osm-3 mutants and also show the
      expression of the gene in IL2 neurons. Temporally, the gene is differentially
      expressed in all three types of chemosensory sensilla. Further work on osm-3, unc
      104 and unc-116 mutants should give insight into the in vivo functions of the
      kinesin family during C. elegans neurogenesis.

PMID- 7714895
TI  - Folding mediated by an intramolecular chaperone: autoprocessing pathway of the
      precursor resolved via a substrate assisted catalysis mechanism.
AB  - Subtilisin is synthesized with an N-terminal propeptide which has been
      demonstrated to function as an intramolecular chaperone that is only essential
      for the folding of the active enzyme. After folding, the propeptide is removed
      via an intramolecular autoprocessing mechanism. This mechanism is blocked when
      His64, a member of the catalytic triad is substituted with Ala. However, an
      additional mutation in the propeptide substituting Glu-2 with His was able to
      suppress the His64Ala mutation, allowing autoprocessing of the propeptide. This
      suppression is considered to be due to a "substrate assisted catalysis" mechanism
      and demonstrates that the cleavage to the subtilisin propeptide is an
      autocatalytic process.

PMID- 7714896
TI  - A basic tail increases repression by dimeric lac repressor.
AB  - Tetrameric Lac repressor achieves cooperative repression by binding
      simultaneously to O1 and to one of the auxiliary operators O2 or O3, thereby
      forcing the intervening DNA into a loop. Dimeric Lac repressor is not able to
      form DNA loops and consequently shows no cooperative repression. We constructed a
      dimeric Lac repressor mutant which exhibits increased repression to the lac
      operon that does not depend on specific operator-repressor-operator loops. This
      Lac repressor carries a synthetic tail of basic residues attached to its C
      terminus. With this construct, we observe an increase of the in vivo repression
      upon addition of auxiliary lac operators to a chromosomal lac operon controlled
      by O1. This suggests that the basic tail enables dimeric Lac repressor to enhance
      its repression by additional non-specific DNA contacts.

PMID- 7714897
TI  - Unwinding of closed circular DNA by the Escherichia coli RuvA and RuvB
      recombination/repair proteins.
AB  - The RuvA and RuvB proteins of Escherichia coli promote the branch migration of
      Holliday junctions during genetic recombination and the recombinational repair of
      damaged DNA. Using a topological assay that measures the underwinding of
      covalently closed duplex DNA, we find that RuvA and RuvB promote the transient
      unwinding of relaxed or supercoiled DNA. Detection of unwinding by RuvAB requires
      the presence of ATP and a non-hydrolysable ATP analogue (ATP gamma S), and was
      not observed in the presence of ATP or ATP gamma S alone. These results indicate
      that RuvAB catalyse the unwinding and rewinding of duplex DNA via an intermediate
      that can be stabilised by the presence a non-hydrolysable cofactor. At elevated
      concentrations of Mg2+ (12 to 30 mM), which are known to favour RuvB binding to
      DNA without the need for RuvA, RuvB protein alone promotes DNA unwinding. These
      results show that RuvB protein, an ATPase that forms hexameric ring structures
      that encircle the DNA, is directly responsible for the DNA unwinding activity
      exhibited by RuvAB. From these results, we propose that branch migration of
      Holliday junctions by RuvAB occurs by the passage of double-stranded DNA through
      the RuvAB complex, in a reaction coupled to transient DNA unwinding.

PMID- 7714898
TI  - Dispersion and insertion polymorphism in two small subfamilies of recently
      amplified human Alu repeats.
AB  - Newly isolated members of two recently propagated (young) Alu subfamilies were
      examined for sequence diversity and insertion polymorphism in primate genomes.
      The smaller subfamily (termed HS-2) is comprised of approximately 5 to 25
      members, while the larger (termed Sb2) includes approximately 125 to 600 members.
      Individual members of these Alu subfamilies share distinguishing sets of
      diagnostic mutations, are well-conserved relative to each other, and have
      expanded in the human lineage. At least one member from each subfamily is known
      to be polymorphic in humans. Three newly characterized HS-2 Alu family members as
      well as three Sb2 Alu repeats are monomorphic (fixed) in humans. The existence of
      a number of Alu subfamilies that have amplified in parallel within the human
      genome provides compelling evidence for the simultaneous activity of multiple
      dispersed Alu source genes.

PMID- 7714899
TI  - Phage HK022 Nun protein arrests transcription on phage lambda DNA in vitro and
      competes with the phage lambda N antitermination protein.
AB  - Phage HK022 Nun protein excludes phage lambda by terminating transcription near
      the lambda nut sites. We have established a purified in vitro system that
      reproduces the in vivo sequence and factor requirements of Nun. Nun arrests
      transcription by E. coli RNA polymerase at or near elongation pause sites distal
      to the nut sites. The boxB sequence of nut is required for optimal Nun activity;
      boxA plays a lesser role. The efficiency of transcription arrest is strongly
      enhanced by the four E. coli Nus factors. The factors increase the specific
      activity of Nun, and allow it to act at higher ribonucleoside triphosphate
      concentrations. A wild-type boxA is required for stimulation by Nus factors. Nun
      and the lambda N antitermination protein compete for their opposing reactions.
      This competition may be at the level of binding of boxB RNA.

PMID- 7714900
TI  - Molecular phylogeny and evolutionary timescale for the family of mammalian
      herpesviruses.
AB  - A detailed phylogenetic analysis for mammalian members of the family
      Herpesviridae, based on molecular sequences is reported. Sets of encoded amino
      acid sequences were collected for eight well conserved genes that are common to
      mammalian herpesviruses. Phylogenetic trees were inferred from alignments of
      these sequence sets using both maximum parsimony and distance methods, and
      evaluated by bootstrap analysis. In all cases the three recognised subfamilies
      (Alpha-, Beta- and Gammaherpesvirinae), and major sublineages in each subfamily,
      were clearly distinguished, but within sublineages some finer details of
      branching were incompletely resolved. Multiple-gene sets were assembled to give a
      broadly based tree. The root position of the tree was estimated by assuming a
      constant molecular clock and also by analysis of one herpesviral gene set (that
      encoding uracil-DNA glycosylase) using cellular homologues as outgroups. Both
      procedures placed the root between the Alphaherpesvirinae and the other two
      subfamilies. Substitution rates were calculated for the combined gene sets based
      on a previous estimate for alphaherpesviral UL27 genes, where the time base had
      been obtained according to the hypothesis of cospeciation of virus and host
      lineages. Assuming a constant molecular clock, it was then estimated that the
      three subfamilies arose approximately 180 to 220 million years ago, that major
      sublineages within subfamilies were probably generated before the mammalian
      radiation of 80 to 60 million years ago, and that speciations within sublineages
      took place in the last 80 million years, probably with a major component of
      cospeciation with host lineages.

PMID- 7714901
TI  - Reptile heme protein structure: X-ray crystallographic study of the aquo-met and
      cyano-met derivatives of the loggerhead sea turtle (Caretta caretta) myoglobin at
      2.0 A resolution.
AB  - The X-ray crystal structures of the aquo-met and cyano-met derivatives of the
      loggerhead sea turtle (Caretta caretta) myoglobin have been determined at 2.0 A
      resolution (R = 0.182, and 0.178, respectively). The results here reported,
      representing the first reptile globin solved by X-ray crystallography, have been
      analyzed in parallel with data for related monomeric hemoproteins, and indicate a
      strong overall structural similarity between the loggerhead sea turtle and
      mammalian myoglobins, reflected by the 63% amino acid identity of their primary
      structures. The root-mean-square deviation between the entire polypeptide
      backbones of loggerhead sea turtle and sperm whale myoglobins, after structure
      superposition, is 0.83 A. Upon cyanide binding to the protein distal site, the
      iron-bound water molecule present in the aquo-met form is displaced by the
      incoming ligand. Cyanide is oriented towards the inner part of the heme distal
      site forming a Fe-C-N angle of 133 degrees.

PMID- 7714902
TI  - Crystal and molecular structures of human progastricsin at 1.62 A resolution.
AB  - The crystal and molecular structures of human progastricsin (hPGC) have been
      determined using multiple isomorphous replacement methods and anomalous
      scattering in conjunction with a phased translation function. The structure has
      been refined to a conventional R-factor (= sigma parallel Fo magnitude of -
      magnitude of Fc parallel / sigma magnitude of Fo magnitude of) of 0.179 with data
      to 1.62 A resolution. The first 37 amino acid residues of the prosegment are
      similar in conformation to the equivalent residues of porcine pepsinogen (pPGN).
      As in pPGN, the N zeta atom of Lys37p sits between the active-site carboxylate
      groups of Asp32 and Asp217, thereby preventing catalysis. The side-chains of
      Tyr38p and Tyr9 sit in the S1' and S1 substrate-binding pockets of hPGC,
      respectively, in an analogous manner to what is observed in porcine pepsinogen.
      There are large conformational differences centered around the region containing
      residues Arg39p to Pro6, relative to the equivalent region in the structure of
      pPGN. Two surface loops in the vicinity of this segment are also displaced
      relative to those in pPGN and in mature aspartic proteinases (Phe71 to Thr81 (the
      "flap"), and Tyr125 to Thr131). In hPGC, Tyr75 O eta does not make its usual
      hydrogen bond to Trp39 N epsilon 1. Rather, the "flap" containing Tyr75 is
      excluded from the active site by the polypeptide segment Arg39p to Pro6. However,
      the conformation of the inhibitory segment, Lys37p to Tyr38p, is virtually
      identical with that observed in pPGN. Hence the structures of these two proteins
      indicate that aspartic proteinase zymogens keep themselves inactive at neutral pH
      by a very similar mechanism in human progastricsin and porcine pepsinogen. This
      similarity likely carries over to all members of both the pepsinogen A and C
      families of aspartic proteinase zymogens.

PMID- 7714904
TI  - Morphology of complex lymphoepithelial organs of the anal canal ("anal tonsil")
      in the bottlenose dolphin, Tursiops truncatus.
AB  - A complex of lymphoepithelial organs, the "anal tonsils," is a consistent
      structure in the anal canal of the bottlenose dolphin, Tursiops truncatus. This
      complex occurs as a circumferential cluster of discrete tonsil-like aggregations
      of lymphoid tissues, together with epithelial ducts ("crypts") and occasional
      mucus secretory units in the extreme lower portion of the intestinal tract. These
      structures are concentrated in the segment lined by stratified squamous
      epithelium and extend for a variable distance cephalad from the anal aperture.
      The tonsils appear to be most active, judged by the amount of lymphoid tissue
      present, in young animals. Depletion of lymphocytes and cystic enlargement of the
      crypts, probably representing functional as well as morphological involution, is
      a consistent feature of older animals.

PMID- 7714903
TI  - Molecular dynamics simulations of protein unfolding and limited refolding:
      characterization of partially unfolded states of ubiquitin in 60% methanol and in
      water.
AB  - Extensive experimental data are available on the native, partially and fully
      unfolded states of ubiquitin. Two and three-dimensional NMR experiments of a
      partially unfolded form of the protein in 60% methanol indicate that
      approximately one-half of the molecule contains disrupted but native-like
      structure while the other half is unstructured and/or contains non-native
      structure. In contrast, the interpretation of hydrogen-exchange data have led to
      the conclusion that this state is native-like. Thus, there are discrepancies
      between the experimental studies, or interpretations based on the data. We
      compare the results of molecular dynamics simulations, under varying conditions,
      with the experimental results. The simulations extend past 0.5 ns and include
      explicit solvent molecules: either pure water or 60% methanol. To begin with,
      ubiquitin was thermally denatured in water (at 498 K). Two particular structures,
      or "aliquots", during the unfolding process were selected for further study (60
      and 198 ps). These structures were then simulated separately in water and 60%
      methanol at a lower and experimentally meaningful temperature (335 K). The
      conformations generated from the structure extracted later in the simulation
      contained significant amounts of non-native structure in the presence of methanol
      while satisfying both the NMR and hydrogen exchange data. In fact, clearly non
      native regions of the structure yielded the desired protection from hydrogen
      exchange. In contrast, an earlier, more native-like, intermediate did not do as
      well at predicting the hydrogen-exchange behavior and was inconsistent with the
      NMR data. These data suggest that the results and interpretations using the
      different experimental techniques can be reconciled by a single state. This
      finding also brings into question the practice of interpreting protection to
      hydrogen exchange in terms of native secondary and tertiary structure, especially
      when one has weak patterns and low protection factors. When the partially
      unfolded states were placed in pure water, the protein collapsed and began to
      refold. Therefore, the desired solvent-dependent properties were observed: the
      partially unfolded conformations with increased exposure of hydrophobic residues
      remained expanded in methanol but collapsed in water as the non-polar groups
      minimized their exposure to solvent.

PMID- 7714905
TI  - Prenatal development of the integument in Delphinidae (Cetacea: Odontoceti).
AB  - The prenatal development of epidermis, dermis, and hypodermis was studied in
      embryos of different age of two delphinid species (Stenella attenuata, Delphinus
      delphis), using light and transmission electron microscopical methods. The
      delphinid embryo is covered by a multilayered tissue formed by four different
      epidermal generations (periderm, stratum intermedium-I, str. intermedium-II, str.
      spinosum) produced by the str. basale. The first layer appears at about 40-50 mm
      of body length, the second type (s.i.-I) about 60-160 mm, and the third type
      (s.i.-II) is present at 160-500 mm. The first spinosal cells are produced at 225
      260 mm body length; thenceforth, the epidermis increases continuously in
      thickness. Epidermal ridge formation begins about 400-mm body length. The
      development of the dermis is characterized by the early production of thin
      connective tissue fibers (40-70-mm body length) and simultaneously the cutaneous
      muscle matures in structure. Vascular development intensifies between embryos of
      150-225 mm, and collagen production increases markedly in fetuses of 225-260-mm
      length. These events are paralleled by an increase in dermal thickness. The first
      elastic fibers can be recognized in the skin from the abdomen at about 600-mm
      body length. The development of the hypodermis is marked by very rapid and
      constantly progressing growth, beginning about 60-mm body length. The first
      typical fat cells appear in animals of 360-400 mm. Regional differences are
      obvious for all skin layers with regard to the flippers, where structural
      maturation proceeds more rapidly than in dorsal or abdominal regions.

PMID- 7714906
TI  - Cephalic morphology of the honey possum, Tarsipes rostratus (Marsupialia:
      Tarsipedidae); an obligate nectarivore.
AB  - The sharply tapering skull of the honey possum is delicately constructed and has
      only a few, minute teeth; its mandible is reduced to a thin, flexible rod. The
      mandibular fossa has been displaced caudally to the caudomedial corner of the
      squamosal. Head skeletons of the feathertail glider and western pygmy-possum,
      omnivores that are closely related to the honey possum, bear greater resemblance
      to the distantly related carnivorous fat-tailed dunnart than to the honey possum.
      Selected muscles associated with the jaws, hyoid, and tongue of these four mouse
      sized (9-22 g) marsupials are described for the first time. The honey possum is
      characterized by a greatly reduced temporalis that is almost completely hidden by
      the eye. Its digastric consists of a single belly that inserts onto the caudal
      margin of the mylohyoid. The lateral pterygoid is relatively long as it extends
      caudally to insert onto the elongated mandible. The stylohyoid originates high up
      on the caudal surface of the tympanic bulla; it curves around the caudal and
      ventral surfaces of the bulla to reach the basihyoid. The insertion of the
      genioglossus is restricted to the caudal quarter of the tongue. Homologous
      muscles of the feathertail glider and western pygmy-possum are more similar to
      those of the fat-tailed dunnart. In addition to the very different
      musculoskeletal system, the honey possum has an unusual tongue that tapers to a
      fine point.

PMID- 7714907
TI  - Development of the interphotoreceptor matrix in Xenopus laevis.
AB  - Xenopus laevis interphotoreceptor matrix (IPM) contains a relatively aqueous
      insoluble wheat germ agglutinin (WGA)-binding component containing unidentified
      sialoglycoconjugates (Wood et al [1984] J. Comp. Neurol. 228:299-307). The
      appearance of WGA-binding macromolecules in the IPM was assessed during late
      embryonic stages (32-45) and in retinal rudiment cultures, using lectin
      cytochemistry and Western blotting techniques. Metabolic labeling of the neural
      retina versus retinal pigment epithelium (RPE)-choroid of juvenile Xenopus with
      35S-MET was also evaluated in vivo and in vitro. Lectin cytochemistry of eyes
      from developmental stages 32-42 demonstrated distinct WGA-ferritin-binding sites
      on the developing outer segment membranes and in the IPM compartment. At stages
      44-46 extensive WGA-binding domains were present as an extracellular network with
      other randomly scattered domains near the retinal pigment epithelium. Retinal
      rudiments from stage 32-33 were isolated and allowed to differentiate in hanging
      drop culture (Hollyfield and Witkowsky [1974] J. Exp. Zool. 189:357-377) with or
      without an investing pigment epithelium. Cultures developing with RPE exhibited
      an elaborate IPM with an anastomosing meshwork of WGA-ferritin binding sites. In
      the absence of RPE only limited amounts of binding restricted to the immediate
      vicinity of the developing photoreceptor outer segment membranes was observed.
      When Western blots were probed with WGA-HRP, stage 32-45 retinas demonstrated a
      major WGA-binding band of 126 kD. Similar amounts of WGA-binding macromolecules
      were synthesized in preparations cultured in the presence or absence of the
      investing RPE. During development the major WGA-binding component is a 126-kD
      protein. Equivalent synthesis of this protein in the presence and absence of RPE
      suggests that the PE is not required for synthesis of this 126-kD component.
      These results suggest that the retina is the primary site of synthesis of the WGA
      binding components of the Xenopus IPM, whereas the PE plays a principal role in
      their assembly and organization.

PMID- 7714908
TI  - Active sites of ligands and their receptors are made of common peptides that are
      also found elsewhere.
AB  - The simultaneous emergence in evolution of a ligand and its receptor might have
      entailed their active sites being drawn from the pool of common oligopeptides.
      This was tested on the principal components of cell-matrix interaction: the RGD
      (Arg-Gly-Asp) site of matrix proteins and the EKKD (Gly-Lys-Lys-Asp) site of
      integrin cell-surface receptor. In the 32 diverse proteins scrutinized, which
      totalled 14,806 residues, there were 104 Arg-Gly dipeptides. Most common of the
      tripeptides beginning with Arg-Gly were Arg-Gly-Leu, Arg-Gly-Gly, and Arg-Gly
      Asp; each was found in ten copies. RGD tripeptide was one of the commonest; the
      fortuitous presence of an RGD site was noted in two enzymes, fibrinogen, a
      pituitary hormone precursor, and a viral structural protein. The 32 proteins also
      contained 121 Lys-Lys dipeptides. Of the tetrapeptides centered by Lys-Lys, the
      commonest was Lys-Lys-Lys-Lys, in four copies. Second most common were Gly-Lys
      Lys-Lys, Val-Lys-Lys-Leu, and Glu-Lys-Lys-Asp; each occurred in three copies. The
      fortuitous presence of an EKKD site was noted in three proteins--an intracellular
      transport protein, a pituitary hormone precursor and a protein of the
      cerebrospinal fluid. In most instances, protein-protein interaction between the
      fortuitously present active sites appears to bring about deleterious
      consequences. Occasionally, however, the fortuitous active site appears to confer
      a new function to a protein bearing it.

PMID- 7714909
TI  - Frequencies of synonymous substitutions in mammals are gene-specific and
      correlated with frequencies of nonsynonymous substitutions.
AB  - The frequencies of synonymous substitutions of mammalian genes cover a much wider
      range than previously thought. We report here that the different frequencies
      found in homologous genes from a given mammalian pair are correlated with those
      in the same homologous genes from a different mammalian pair. This indicates that
      the frequencies of synonymous substitutions are gene-specific (as are the
      frequencies of nonsynonymous substitutions), or, in other words, that "fast" and
      "slow" genes in one mammal are fast and slow, respectively, in any other one.
      Moreover, the frequencies of synonymous substitutions are correlated with the
      frequencies of nonsynonymous substitution in the same genes.

PMID- 7714910
TI  - Gypsy/Ty3-class retrotransposons integrated in the DNA of herring, tunicate, and
      echinoderms.
AB  - Eight new examples of retrotransposons of the Gypsy/Ty3 class have been
      identified in marine species. A 525-nt pol gene-coding region was amplified using
      degenerate primers from highly conserved regions and has extended the range of
      recognition of Gypsy/Ty3 far beyond those previously known. The following matrix
      shows the percentage AA divergence of the translations of this segment of the pol
      gene coding region. [table: see text] The underlines separate three groups of
      retrotransposons that can be recognized on the basis of this amino acid sequence.
      The new upper group shows surprising amino acid sequence similarity among members
      from the DNA of herring, sea urchin, starfish, and a tunicate. For example, the
      herring element differs by only 41% from the Ciona element and 46% from the sea
      urchin element. The group between the lines includes members close to previously
      known elements (marked by asterisks) and has so far been found only in sea
      urchins. The two upper groups differ from each other by 55-60% and yet members of
      both groups (e.g., Spr1 and Spr2) are integrated into the DNA of one species--S.
      purpuratus. Below the lower underline is listed the only known representative of
      a very distant group, which occurs in starfish DNA. In spite of large divergence,
      amino acid sequence comparisons indicate that all of the elements shown in the
      array are members of the LTR-containing class of retrotransposons that includes
      Gypsy of Drosophila and Ty3 of yeast. Of all known mobile elements this class
      shows the closest sequence similarity to retroviruses and has the same
      arrangement of genes as simpler retroviruses.

PMID- 7714911
TI  - Evidence on primate phylogeny from epsilon-globin gene sequences and flanking
      regions.
AB  - Phylogenetic relationships among various primate groups were examined based on
      sequences of epsilon-globin genes. epsilon-globin genes were sequenced from five
      species of strepsirhine primates. These sequences were aligned and compared with
      other known primate epsilon-globin sequences, including data from two additional
      strepsirhine species, one species of tarsier, 19 species of New World monkeys
      (representing all extant genera), and five species of catarrhines. In addition, a
      2-kb segment upstream of the epsilon-globin gene was sequenced in two of the five
      strepsirhines examined. This upstream sequence was aligned with five other
      species of primates for which data are available in this segment. Domestic rabbit
      and goat were used as outgroups. This analysis supports the monophyly of order
      Primates but does not support the traditional prosimian grouping of tarsiers,
      lorisoids, and lemuroids; rather it supports the sister grouping of tarsiers and
      anthropoids into Haplorhini and the sister grouping of lorisoids and lemuroids
      into Strepsirhini. The mouse lemur (Microcebus murinus) and dwarf lemur
      (Cheirogaleus medius) appear to be most closely related to each other, forming a
      clade with the lemuroids, and are probably not closely related to the lorisoids,
      as suggested by some morphological studies. Analysis of the epsilon-globin data
      supports the hypothesis that the aye-aye (Daubentonia madagascariensis) shares a
      sister-group relationship with other Malagasy strepsirhines (all being classified
      as lemuroids). Relationships among ceboids agree with findings from a previous
      epsilon-globin study in which fewer outgroup taxa were employed. Rates of
      molecular evolution were higher in lorisoids than in lemuroids.

PMID- 7714912
TI  - Synonymous and nonsynonymous substitutions in mammalian genes and the nearly
      neutral theory.
AB  - The nearly neutral theory of molecular evolution predicts larger generation-time
      effects for synonymous than for nonsynonymous substitutions. This prediction is
      tested using the sequences of 49 single-copy genes by calculating the average and
      variance of synonymous and nonsynonymous substitutions in mammalian star
      phylogenies (rodentia, artiodactyla, and primates). The average pattern of the 49
      genes supports the prediction of the nearly neutral theory, with some notable
      exceptions. The nearly neutral theory also predicts that the variance of the
      evolutionary rate is larger than the value predicted by the completely neutral
      theory. This prediction is tested by examining the dispersion index (ratio of the
      variance to the mean), which is positively correlated with the average
      substitution number. After weighting by the lineage effects, this correlation
      almost disappears for nonsynonymous substitutions, but not quite so for
      synonymous substitutions. After weighting, the dispersion indices of both
      synonymous and nonsynonymous substitutions still exceed values expected under the
      simple Poisson process. The results indicate that both the systematic bias in
      evolutionary rate among the lineages and the episodic type of rate variation are
      contributing to the large variance. The former is more significant to synonymous
      substitutions than to nonsynonymous substitutions. Isochore evolution may be
      similar to synonymous substitutions. The rate and pattern found here are
      consistent with the nearly neutral theory, such that the relative contributions
      of drift and selection differ between the two types of substitutions. The results
      are also consistent with Gillespie's episodic selection theory.

PMID- 7714913
TI  - Estimating the intensity of male-driven evolution in rodents by using X-linked
      and Y-linked Ube 1 genes and pseudogenes.
AB  - Using sequence data from the last introns of ZFX and ZFY genes, we previously
      estimated the male-to-female ratio (alpha) of mutation rate to be close to 6 in
      higher primates and 1.8 in rodents. As the mutation rate may vary among different
      regions of the mammalian genome, it is interesting to see whether sequence data
      from other regions will give similar estimates. In this study, we have determined
      the partial genomic sequences of the ubiquitin-activating enzyme E1 genes (Ube 1x
      and Ube 1y for the X-linked and Y-linked homologues, respectively) of mice and
      rats and two mouse Ube 1y pseudogenes. From the intron sequences of the Ube 1
      genes, we calculated the divergence of the Y-linked genes (Y = 0.161) and that of
      the X-linked genes (X = 0.107) between mouse and rat, and found the Y/X ratio to
      be 1.50. This ratio led to an estimate of alpha = 2.0 with a 95% confidence
      interval of (1.0, 3.9). Similar estimates of alpha were obtained if mouse Ube 1y
      pseudogenes were used instead of the mouse Ube 1y functional gene. These
      estimates are consistent with our previous estimate for rodents and suggest that
      the sex ratio of mutation rate in rodents is approximately only one-third of that
      in higher primates. Our estimate of the divergence time between Ube 1x and Ube 1y
      supports the view that the two genes separated before the eutherian radiation.

PMID- 7714914
TI  - A molecular view of pinniped relationships with particular emphasis on the true
      seals.
AB  - Phylogenetic analysis of conservative nucleotide substitutions in 18 complete
      sequences of the mitochondrial cytochrome b gene of Phocidae (true seals),
      Odobenidae (walruses), and Otariidae (sea lions and fur seals), plus three ursid
      and three felid sequences, identified the pinnipeds as monophyletic with
      Otariidae and Odobenidae on a common evolutionary branch. Analysis of total
      nucleotide differences separated the evolutionary lineages of northern and
      southern phocids. Both lineages are distinct from the most ancestral phocid
      genus, Monachus (monk seals), represented by the Hawaiian monk seal. The
      inclusion of the Hawaiian monk seal in the subfamily Monachinae makes the
      subfamily paraphyletic. Among the northern phocids, the hooded seal (genus
      Cystophora, chromosome number 2n = 34) is sister taxon to the Phoca complex. The
      Phoca complex, which is characterized by the chromosome number 2n = 32, includes
      genus Phoca and the monotypic genus Halichoerus (grey seal). The comparison does
      not support a generic distinction of Halichoerus within the Phoca complex. The
      present data suggest that Cystophora and Phoca separated > or = 6 million years
      ago. Among the southern phocids the close molecular relationship of the Weddell
      and leopard seals relative to their morphological distinction exemplifies rapid
      adaptation to different ecological niches. This result stands in contrast to the
      limited morphological differentiation relative to the pronounced molecular
      distinctions that may occur within the Phoca complex.

PMID- 7714915
TI  - Genetics of selection-induced mutations: I. uvrA, uvrB, uvrC, and uvrD are
      selection-induced specific mutator loci.
AB  - Selection-induced mutations, sometimes called "directed," "adaptive," or
      "Cairnsian" mutations, are spontaneous mutations that occur as specific responses
      to environmental challenges, usually during periods of prolonged stress, and that
      occur more often when they are selectively advantageous than when they are
      selectively neutral. In this study I show that lesions in uvrA, uvrB, uvrC, or
      uvrD increase the mutation rate from trpA46 to trpA+ by 10(2)- to 10(4)-fold
      during tryptophan starvation, but those same lesions do not affect random
      mutation rates in growing cells when tryptophan is present. The increased
      selection-induced mutation rates remain specific to the gene that is under
      selection in that no increase in the mutation rate from trpA46 to trpA+ is
      detected during proline starvation. Evidence is presented showing that proline
      starvation produces a state of cellular stress which results in a burst of
      mutations from trpA46 to trpA+ when proline-starved cells are plated onto medium
      lacking tryptophan but containing proline. These results are consistent with the
      hypermutable state model for selection-induced mutagenesis.

PMID- 7714916
TI  - NGF protects PC12 cells against ischemia by a mechanism that requires the N
      kinase.
AB  - Nerve growth factor (NGF), which has been shown to act as a morphological and
      neurochemical differentiating factor in PC12 cells, also protects PC12 cells from
      the toxicity of serum withdrawal and ischemia. By using a previously established
      in vitro model of ischemia, which incorporates the combination of anoxia with
      glucose deprivation (Boniece and Wagner: J Neurosci 13:4220-4228, 1993), we have
      been able to study the signal transduction pathways upon which NGF-induced
      survival is dependent. Here we demonstrate that inhibitors of the N-kinase and
      NGF-induced neuritogenesis, 6-thioguanine and 2-aminopurine, prevent the
      protective effects of NGF, while they have little, if any, effect on the
      protection conferred by epidermal growth factor (EGF) or dbcAMP. This suggests
      that only NGF acts by a mechanism that depends strongly on the N-kinase.
      Furthermore, the methyltransferase inhibitor 5'-deoxy-5'-methylthioadenosine
      (MTA), which also inhibits NGF-induced neuritogenesis, inhibits the protective
      effect of NGF but not the protective effects of EGF or dbcAMP. Thus, the
      neuroprotective effect of NGF requires some of the same signal transduction steps
      used by NGF to promote differentiation and neurite formation. Furthermore, we
      found that exposure of PC12 cells to retinoic acid, which promotes the
      differentiation and inhibits the growth of PC12 cells, also improves cell
      survival during ischemia. In addition, a combination of NGF and retinoic acid was
      more effective than either agent alone. It is likely that these two agents confer
      protection by independent pathways.

PMID- 7714917
TI  - Effect of persistent mouse hepatitis virus infection on MHC class I expression in
      murine astrocytes.
AB  - Neurotropic strains of mouse hepatitis virus (MHV) have been used extensively for
      the study of viral pathogenesis in the central nervous system (CNS), serving as
      models for human neurological diseases such as multiple sclerosis (MS). MHV
      strains A59 and JHMV both cause acute and chronic encephalomyelitis and
      demyelination in susceptible strains of mice and rats. In acute disease, CNS
      damage is most likely the result of lytic infection in neurons and
      oligodendrocytes, and death can be prevented by the adoptive transfer of Class I
      restricted CD8+ T cells. However, in later stages of the disease induced by some
      MHV strains, virus tends to be restricted to astrocytes in a nonlytic infection,
      and the immune response appears to contribute to CNS damage. These data lead us
      to suggest that the astrocyte may play a central role in the neuropathogenesis of
      MHV infection. Consistent with this possibility, A59 has been reported to induce
      the expression of Class I molecules of the major histocompatibility complex (MHC)
      in glial cells following infection in vivo and in vitro. In this communication,
      we have examined the influence of persistent infection by both A59 and JHMV on
      MHC Class I expression in primary murine astrocytes. Persistence was
      characterized by the presence of intracellular viral antigen and mRNA in the
      absence of detectable infectious virus particles. Under these conditions, JHMV,
      but not A59, inhibited constitutive expression of the H-2 Kb molecule, with the
      magnitude of inhibition increasing with postinfection time. A59 was not able to
      induce Class I during persistence, presumably due to the lack of infectious virus
      particles. Class I expression was restored by the addition of gamma-interferon
      (IFN-gamma) to astrocytes persistently infected with either A59 or JHMV. Thus,
      Class I inhibition is not a permanent consequence of JHMV persistence, and
      persistence does not interfere with normal signalling pathways for Class I
      induction.

PMID- 7714918
TI  - Nerve growth factor-activated protein kinase N modulates the cAMP-dependent
      protein kinase.
AB  - Protein kinase N (PKN) is a serine/threonine protein kinase rapidly activated by
      nerve growth factor (NGF) and other agents in various cell lines. The possible
      involvement of PKN in the multiple pathways of the NGF mechanism of action was
      previously established through the use of purine analogs, some of which are
      apparently specific inhibitors of this kinase. Since a PKN-like activity is
      modulated in several cell lines by cAMP analogs and this activation requires the
      activity of cAMP-dependent protein kinase, the aim of the present work is to
      investigate possible interactions between PKN and C-PKA. Pre-incubation of the
      two kinases in the presence of ATP leads to potentiated phosphorylation of
      histone HF1, Kemptide (a substrate for C-PKA, but not for PKN), and several
      additional substrates. This augmented phosphorylating activity is insensitive to
      6-thioguanine (an inhibitor for PKN, but not for C-PKA) and is suppressed both by
      the Walsh inhibitor and by the regulatory subunit of PKA. PKN-pretreated C-PKA
      shows a significant decrease in Km for Kemptide and a substantial increase in
      Vmax. C-PKA and PKN are widely expressed enzymes and the possibility of PKN
      dependent modulation of PKA in intact cells would therefore have biological
      implications for signal transduction mechanisms.

PMID- 7714919
TI  - Survival, development, and electrical activity of central nervous system
      myelinated axons exposed to tumor necrosis factor in vitro.
AB  - Spinal cord explants from CD-1 mouse embryos were cultured in Maximow slide
      assemblies to promote myelin development. At about 20 days in vitro, recombinant
      human or mouse tumor necrosis factor alpha (TNF alpha) was added. Observed 3-8
      days later, myelin was largely intact. The myelin blistering and oligodendrocyte
      damage seen in other strains were generally absent. Axonal conduction was
      measured optically through the use of a voltage-sensitive dye. Action potential
      shape, conduction velocity, and refractory period were all unchanged by exposure
      to TNF alpha. Two series of explants were grown with TNF alpha present
      continuously throughout the culture period. Observed with light and electron
      microscopy, myelin developed in at least 50% of the explants treated with
      recombinant mouse TNF alpha and 80% of those exposed to recombinant human TNF
      alpha. Optically recorded action potentials were of normal shape and refractory
      period. Conduction velocities were slightly lower than controls. CD-1 mouse
      central nervous system contains TNF alpha receptors and yet was resistant to
      myelin damage. The apparent strain specificity of TNF alpha disruption of myelin
      may result from more indirect modes of action, including interaction with other
      cytokines produced by glial cells. Survival of axonal conduction suggests that
      Na+ channel function remains intact following TNF alpha exposure.

PMID- 7714920
TI  - Transforming growth factor-beta 1 inhibits the proliferation of rat astrocytes
      induced by serum and growth factors.
AB  - A number of cytokines and growth factors may affect astrocyte proliferation and
      functions. Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotropic
      cytokine which exerts multiple effects on growth and differentiation of different
      cell types. TGF-beta 1 is present in low amounts in the normal brain. TGF-beta 1
      gene expression, however, is increased in the central nervous system (CNS) in
      several pathological conditions. In this study we examined the in vitro effects
      of TGF-beta 1 on the proliferative response of rat astrocytes to serum and growth
      factors. Astrocyte cultures were established from the cerebellum and cortex of
      newborn Lewis rats. The proliferative response of these cultures to serum and
      growth factors [platelet-derived growth factor (PDGF), basic fibroblast growth
      factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor 1 (IGF
      1), IGF-2, interleukin 1 (IL-1)] was studied by [3H]-thymidine incorporation test
      in the presence or absence of TGF-beta 1. TGF-beta 1 significantly inhibited the
      proliferative response of astrocyte cultures to both autologous and heterologous
      serum. In addition, a strong inhibition of bFGF-, EGF-, and PDGF-induced
      proliferation was observed. The effect of TGF-beta 1 on the proliferative
      response to IL-1 was less evident but still significant. No effect was observed
      when TGF-beta 1 was added to IGF-1 and IGF-2 stimulated cultures. These data
      confirm previous reports showing a down-regulating activity of TGF-beta on
      astrocyte proliferation and suggest that this cytokine may play physiological and
      pharmacological roles in the regulation of reactive astrocytosis in the CNS.

PMID- 7714921
TI  - Synaptic vesicle-associated glutamate decarboxylase: identification and
      relationship to insulin-dependent diabetes mellitus.
AB  - Glutamic acid decarboxylase (GAD) catalyzes the biosynthesis of the inhibitory
      neurotransmitter gamma-aminobutyric acid (GABA). GAD has been suggested as an
      autoantigen in insulin-dependent diabetes mellitus and stiff-man syndrome.
      Recently, three forms of membrane-associated GAD (MGAD) have been characterized
      in porcine brain, but the subcellular localization and function of these proteins
      are unknown. We present evidence that GAD activity is associated with synaptic
      vesicles from porcine brain. These vesicles contain a 60 kDa protein recognized
      by serum from patients with insulin-dependent diabetes mellitus, probably MGADII,
      as shown by subcellular fractionation and immunoblotting. These results raise the
      possibility that the association of MGADII with synaptic vesicles may be crucial
      for its role as an autoantigen in insulin-dependent diabetes mellitus.

PMID- 7714922
TI  - Insulin-like growth factors protect against diabetic neuropathy: effects on
      sensory nerve regeneration in rats.
AB  - Neuropathy is an enigmatic and debilitating complication of diabetes. A consensus
      as to the pathogenesis of this disorder has yet to emerge. Recently, it has been
      found that the insulin-like growth factors (IGFs) regulate peripheral nerve
      regeneration, and IGF content is reduced in various diabetic tissues. We tested
      herein the hypothesis that IGF administration can prevent or ameliorate the
      impairment of sensory nerve regeneration in streptozotocin diabetic rats.
      Miniosmotic pumps released small local doses of IGF-I from a catheter routed near
      a site of sciatic nerve crush or larger systemic doses of IGF-I or IGF-II from a
      distant subcutaneous site. Whether administered locally or systemically, IGFs
      protected against the impairment of sensory nerve regeneration. Surprisingly,
      this protection was obtained despite unabated hyperglycemia. Therefore, the
      neuropathy involving sensory nerve regeneration in diabetes can be ameliorated or
      prevented by IGF treatment, independently of hyperglycemia.

PMID- 7714923
TI  - Time course of ciliary neurotrophic factor mRNA expression is coincident with the
      presence of protoplasmic astrocytes in traumatized rat striatum.
AB  - Adrenal grafting for Parkinson's disease has led to modest functional improvement
      despite poor graft survival. One explanation is a neurotrophic response within
      the traumatized striatum. This study was undertaken to investigate the time
      course of the astrocytic response in vivo and in vitro, and the expression of
      ciliary neurotrophic factor (CNTF) mRNA following striatal injury. Unilateral
      stereotaxic biopsy of the rat striatum was performed and gelatin sponge (gel
      foam) was immediately placed into the biopsy cavity. Rats were sacrificed on days
      1, 3, 5, 7, 14, and 28 post biopsy. Immunohistochemical staining of the
      traumatized striatum with antibodies to glial fibrillary acidic protein (GFAP)
      was carried out. The reactive astrocytes which appeared within 7 days after
      trauma were mostly protoplasmic on the basis of morphology, and maximal on day 7,
      being 30 times the level in the normal striatum. After day 7, fibrous astrocytes
      appeared and increased up to day 28, while protoplasmic astrocytes decreased. In
      addition, immunocytochemical double staining of short term cultured astrocytes
      from the traumatized striatum with anti-A2B5 and anti-GFAP antibodies revealed
      that 84% and 90% of astrocytes were type 1 astrocytes on days 3 and 7,
      respectively; however, by day 28 47% of astrocytes were type 2. Northern blot
      analysis revealed that CNTF mRNA expression was up-regulated and peaked on day 7,
      coincident with a predominance of protoplasmic astrocytes in vivo and type 1
      astrocytes in vitro, respectively. These findings suggest that the expression of
      CNTF mRNA is part of the early astrocytic response to trauma, particularly
      associated with protoplasmic astrocytes in vivo and type 1 astrocytes in
      vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714924
TI  - Differential changes in cholinergic markers from selected brain regions after
      specific immunolesion of the rat cholinergic basal forebrain system.
AB  - The aim of this study was to characterize the effects of cortical cholinergic
      denervation on cholinergic parameters in the cerebral cortex and basal forebrain
      using a novel immunotoxin (conjugate of the monoclonal antibody 192IgG against
      the low-affinity nerve growth factor receptor armed with cytotoxin saporin) to
      efficiently and selectively lesion cholinergic neurons in rat basal forebrain.
      Seven days following an intracerebroventricular injection of the cholinergic
      immunotoxin 192IgG-saporin the binding levels of nicotinic and M1- and M2
      muscarinic acetylcholine receptors (mAChR), high-affinity choline uptake sites,
      as well as the m1-m4 mAChR mRNA were determined in coronal brain sections by both
      receptor autoradiography and in situ hybridization, and quantified by image
      analysis. Hemicholinium-3 binding to high-affinity choline uptake sites was
      decreased by up to 45% in all cortical regions and in the hippocampus after a
      single injection of the immunotoxin compared to controls. In contrast, M1-mAChR
      sites were increased over the corresponding control value in the anterior parts
      of cingulate, frontal, and piriform cortex by about 20%, in the hindlimb/forelimb
      areas (18%), in the parietal cortex (35%), in the occipital cortex area 2 (17%),
      as well as in the temporal cortex (25%) following immunolesion. M2-mAChR levels
      were found to be significantly increased in the posterior part of the parietal
      cortex area 1 (by about 22%) and in the occipital cortex area 2 (20%) only. With
      respect to laminar cortical localization, M2-mAChRs and choline uptake sites were
      altered in all cortical layers, whereas M1-mAChRs were preferentially affected in
      the upper cortical layers by the immunolesion. The increase in M1-mAChR binding
      in the temporal and occipital cortex as a consequence of the immunolesion was
      complemented by an increase in the amount of m1 and m3 mAChR mRNA of about 20% in
      these regions. The elevated levels of M2-mAChR sites in the occipital and
      temporal cortex following immunolesion were accompanied by an increase in the m4
      (by 25%) but not m2 mAChR mRNA. There was no effect of the immunolesion on the m1
      m4 mAChR mRNA in frontal cortical regions. in the basal forebrain, however,
      immunolesioning caused about a 40% decrease in the level of m2 mAChR mRNA in the
      medial and lateral septum as well as in the vertical and horizontal limb of the
      diagonal band, whereas M1- and M2-mAChR binding and the levels of m1, m3, and m4
      mAChR mRNA were not affected by the immunolesion in any of the basal forebrain
      nuclei studied.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7714925
TI  - Partial purification of a novel mitogen for oligodendroglia.
AB  - A protein with a MWapp of 50-70 kDa isolated from the salt extract of crude
      membranes from neonatal rat brain increases the numbers of oligodendroglia in
      mixed glial cultures prepared from neonatal rat cerebral white matter. After
      partial purification by ion exchange and gel exclusion chromatography, and
      elution from an SDS-polyacrylamide gel, this protein ("oligodendroglial trophic
      factor," OTF) elicited half-maximal oligodendroglial recruitment at a
      concentration of 5 ng/mL. OTF is a mitogen for oligodendroglia, and to a lesser
      extent, for oligodendroglial progenitor (O2A) cells, but does not stimulate
      proliferation of astroglia, Schwann cells, or endoneurial fibroblasts. OTF,
      unlike platelet-derived growth factor (PDGF), is not an oligodendroglial survival
      factor. Antibodies against PDGF and basic fibroblast growth factor (bFGF) do not
      interfere with the accumulation of oligodendroglia induced by OTF. When OTF is
      given simultaneously with either PDGF or bFGF, there is an additive increase in
      the numbers of cells of the oligodendroglial lineage.

PMID- 7714926
TI  - Differential expression of vomeromodulin and odorant-binding protein, putative
      pheromone and odorant transporters, in the developing rat nasal chemosensory
      mucosae.
AB  - Expression of the putative pheromone and odorant transporter, vomeromodulin, was
      characterized in developing rat nasal mucosae using in situ hybridization and
      immunocytochemistry. Initial expression of vomeromodulin mRNA and protein was
      detected at embryonic day (E)16 in the maxillary sinus component of the lateral
      nasal glands. The abundance of mRNA and protein in the lateral nasal glands
      increased with age and reached a peak at postnatal day (P)27. Also at P27,
      vomeromodulin mRNA and protein expression was initiated in vomeronasal glands and
      posterior glands of the nasal septum. Comparison of the developmental expression
      of odorant-binding protein, another carrier protein synthesized in the lateral
      nasal glands, with that of vomeromodulin demonstrated major differences. In
      contrast to vomeromodulin, odorant-binding protein was not detected until
      postnatal day 2 in the ventral component of the lateral nasal glands and anterior
      glands of the nasal septum. These results suggest that the expression of
      vomeromodulin and odorant-binding protein is developmentally and differentially
      regulated and confirms the suggestion that vomeromodulin may function in
      olfactory and vomeronasal perireceptor processes as a transporter for pheromones
      and odorants. In addition, the embryonic expression of vomeromodulin suggests its
      involvement in olfactory perireceptor processes in utero.

PMID- 7714928
TI  - Reassembly of the 66 kD neurofilament protein in vitro following isolation and
      purification from bovine spinal cord.
AB  - NF-66, also known as alpha-internexin, has been characterized as a 66 kD
      mammalian neurofilament (NF) protein whose expression in developing rat brain
      precedes that of the low molecular weight NF protein (NF-L). NF-66 is thought to
      assemble into 10 nm diameter intermediate filaments in vitro, although the
      precise nature of the assembly process remains obscure. Likewise, the ability of
      NF-66 to polymerize with the low (NF-L), middle (NF-M), and high (NF-H) M(r)NF
      proteins has not been defined. This investigation describes the reassembly of
      bovine NF-66 regarding its formation into 10 nm diameter filaments as well as its
      potential for polymerization with other type IV intermediate filaments. NF-66 and
      the NF triplet proteins were isolated from bovine spinal cord using established
      biochemical extraction and isolation procedures (Balin et al., Brain Res 556:181
      195, 1991), and purified by a combination of high performance liquid
      chromatography (HPLC) (DEAE anion exchange and hydroxylapatite column
      chromatography) and gel elution strategies. In vitro reassembly experiments
      revealed that NF-66 formed approximately 10 nm diameter filaments of varying
      length; immunoelectron microscopy demonstrated labeling of these filaments by a
      monoclonal antibody to intermediate filament antigen (IFA), a polyclonal antibody
      against rat NF-66 and by a monoclonal antibody generated against the core region
      of NF-M but cross-reactive with NF-66. This report is the first investigation to
      look at the in vitro interaction between NF-66 and other type IV intermediate
      filament proteins (NF-H, -M, and -L) and establishes that NF-66 forms
      heteropolymeric filaments with these other neurofilament proteins, as confirmed
      by double immunolabeling. These studies suggest that NF-66 could provide a
      nucleation site for the polymerization of later-expressed proteins during
      neuronal development.

PMID- 7714927
TI  - Acute tolerance to the excitatory effects of opioids in the rat hippocampus.
AB  - Prolonged iontophoretic administrations of delta- and mu-selective opioid
      receptor agonists were conducted in the hippocampus of rats, in order to study
      the possible development of acute tolerance to the excitatory effects of the
      opioids. Acute tolerance (AT) to the excitatory effects of the delta-selective
      opioid receptor agonist Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET) was observed when the
      drug was applied locally for 3-5 min in the CA1 hippocampal pyramidal neurons.
      The acute tolerance was expressed as a decrease in the commissurally evoked spike
      responsiveness during peptide's administration and led to a long-lasting
      potentiation of the population spike (PS) upon its withdrawal. In all cases,
      where AT and spike potentiation were evident, the population excitatory
      postsynaptic potential (pEPSP) remained unaltered. Pharmacological studies of AT
      and long-lasting spike potentiation showed the following: (1) the nonselective
      opioid receptor antagonist, naloxone, while effective in blocking the excitatory
      effects of DSLET when applied prior and during the application of the latter,
      failed to exhibit any effect on the long-lasting potentiating effect of the
      opioid; and (2) during the spike potentiation phase, administration of DSLET
      exhibited a depressant effect towards baseline values. This depressant effect of
      the opioid was evident 2-3 min from the beginning of the application and was
      completely antagonized by naloxone. The above results show that the development
      of acute tolerance to the excitatory effects of the DSLET led to long-lasting
      spike potentiation, which manifests a withdrawal phenomenon.

PMID- 7714929
TI  - Release of endogenous catecholamines from the striatum and bed nucleus of stria
      terminalis evoked by potassium and N-methyl-D-aspartate: in vitro microdialysis
      studies.
AB  - Induced release of endogenous dopamine and noradrenaline from coronal slices
      containing the striatum and the bed nucleus of the stria terminalis,
      respectively, was studied by means of in vitro microdialysis. A Ca(+2)-dependent
      and reserpine-sensitive K(+)-induced release of catecholamines was detected in
      both nuclei. We confirmed that N-methyl-D-aspartate (2.5 and 5.0 mM in the
      dialysis perfusion solution) induces the release of dopamine from the striatum,
      and this effect was blocked by prior dialysis perfusion with 500 microM MK-801, a
      noncompetitive N-methyl-D-aspartate receptor antagonist. Infusion of N-methyl-D
      aspartate (1-10 mM) or glutamate through the dialysis probe did not produce any
      detectable modification in the extracellular levels of noradrenaline in the bed
      nucleus of the stria terminalis. In addition, perfusion with D-serine (100
      microM) alone or in the presence of desipramine (10 microM), resulted in a slight
      increase in extracellular noradrenaline in the bed nucleus of the stria
      terminalis. However, N-methyl-D-aspartate in the presence of D-serine and
      desipramine produced a marked increase in extracellular noradrenaline from the
      bed nucleus of the stria terminalis. These results indicate that N-methyl-D
      aspartate receptors might regulate the release of noradrenaline from the bed
      nucleus of the stria terminalis as is the case of dopamine release in the
      striatum. The in vitro microdialysis seems to be a suitable complement to the in
      vivo microdialysis for the study of catecholamine release in discrete regions of
      the central nervous system and its local regulation by excitatory amino acid
      receptors.

PMID- 7714931
TI  - Microbiological methods for assessing handwashing practice in hygiene behaviour
      studies.
AB  - Personal hygiene, especially handwashing, is frequently mentioned as an important
      aspect of diarrhoeal disease prevention in water and sanitation programmes.
      Handwashing practice is difficult to assess but the microbiological analysis of
      hands shows promise as an indicator of this behaviour. Most methods for isolating
      bacteria from the hands have been developed for use in hospitals in order to
      investigate the spread of nosocomial infections. However, reliable and
      inexpensive methods which need only limited expertise are needed for use in
      developing countries where diarrhoeal diseases remain a major health risk.
      Techniques for sampling hands and bacteriological analysis methods are discussed
      with special emphasis on practical considerations for conducting tests in
      developing countries. Several studies have used these methods successfully and
      have investigated hygiene behaviour and how living conditions affect behaviour
      and the role of hands in diarrhoeal disease transmission. We recommend the use of
      impression plates for isolating faecal indicator bacteria from the hands and also
      recommend faecal streptococci as an indicator of faecal contamination.

PMID- 7714930
TI  - Macrophage recruitment in different models of nerve injury: lysozyme as a marker
      for active phagocytosis.
AB  - Macrophages play critical roles in both degenerative and regenerative processes
      following peripheral nerve injury. These include phagocytosis of debris,
      stimulation of Schwann cell dedifferentiation and proliferation, and salvage of
      myelin lipids for reutilization during regeneration. To better define the role of
      macrophages, we studied models of primary demyelination (tellurium intoxication)
      and secondary demyelination (nerve crush and cut). Sections of paraformaldehyde
      fixed rat sciatic nerves at various stages of demyelination were stained with
      monoclonal antibody ED1, a standard macrophage marker, and a polyclonal antiserum
      specific for lysozyme (LYS). Near the peak of demyelination in all three models,
      LYS immunoreactivity colocalized with ED1 staining. Macrophages present in nerve
      after the period of maximal phagocytosis of myelin were much less immunoreactive
      for LYS. These results suggest LYS is a good marker for macrophages which are
      active in phagocytosis. Tellurium intoxication, which causes synchronous
      demyelination and subsequent remyelination of only about 25% of myelin
      internodes, recruited more macrophages (and induced more lysozyme expression)
      than either nerve crush or cut, which cause demyelination of all internodes
      distal to the injury site. This suggests that Schwann cells may recruit
      macrophages soon after metabolic insult and prior to actual demyelination. The
      final signal for macrophage recruitment is not directly related to the amount of
      damaged myelin. In the models listed above, steady state mRNA levels for
      apolipoprotein E (ApoE; possible mediator of cholesterol salvage), LYS, and P0
      (major structural protein of PNS myelin), were analyzed by Northern blot
      analysis. LYS mRNA levels peaked sharply in all models, with a temporal pattern
      consistent with the expected presence of activated, phagocytic
      macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7714933
TI  - Scrub typhus pneumonitis with delayed resolution.
AB  - A 35-year-old lady was admitted to hospital with fever and dry cough. Chest
      radiograph showed bilateral basal infiltrate. Her Weil-Felix test was strongly
      positive (OX-K > 1:160) and her fever came down with intravenous tetracycline.
      There was no improvement in the lung shadow and spirometry showed a severe
      restrictive defect. Open lung biopsy confirmed the diagnosis of interstitial
      pneumonitis. CT of thorax 6 months after presentation showed partial resolution
      of the interstitial shadow.

PMID- 7714932
TI  - Initial experience of using a knowledge based system for monitoring immunization
      services in Papua New Guinea.
AB  - A knowledge based system (KBS) which helps health service managers to interpret
      immunization coverage rates was installed in two provinces of Papua New Guinea.
      It was assessed over a period of 4 months to determine whether it was a
      potentially useful management tool. One province used the system but did not
      adjust its activities significantly because it was meeting its targets for
      immunization. In the other province the KBS helped provincial managers to detect
      problems and respond to them. Consequently, improvements in performance
      indicators were detected. It is difficult to attribute the improvements entirely
      to the KBS but several actions were taken to strengthen immunization services and
      the KBS appeared to support these. It appears that interventions which make
      routinely collected data more understandable and readily usable by health service
      managers can lead to improvements in the delivery of health services.

PMID- 7714934
TI  - An appraisal of a 'string test' for the detection of small bowel bacterial
      overgrowth.
AB  - The efficacy of a string test for the detection of small bowel bacterial
      overgrowth (SBBO) was determined by comparison with a sterile endoscopic method
      for sampling small bowel secretions in 15 subjects investigated for SBBO.
      Clinical value was found to be limited by poor sensitivity, specificity and
      positive predictive value. The string test is not an adequate substitute for oro
      duodenal intubation for the detection of SBBO.

PMID- 7714935
TI  - Effect of antimicrobial (nalidixic acid) therapy in shigellosis and predictive
      values of outcome variables in patients susceptible or resistant to it.
AB  - We observed the clinical features and results of simple laboratory tests on
      stools of 33 children with bacteriologically proven shigellosis to identify
      features that could be used to assess the effectiveness of antimicrobial therapy.
      Persistence of fever (rectal temperature > 37.8 degrees C), abdominal
      pain/tenderness and anorexia on days 3 and 5 were significantly more common (P <
      0.001) among children who received an antimicrobial to which the infecting
      Shigella was resistant. Similarly, a significantly higher number of children
      treated with an ineffective antimicrobial had faecal leucocytes of > 50/high
      power microscopic field (HPF), erythrocytes of > 50/HPF and macrophages of >
      5/HPF on study day 5. The best predictors of ineffective antimicrobial therapy on
      days 3 and 5 of treatment were fever, presence of blood by naked eye examination
      of stool, and minimum change in stool frequencies. These observations suggest
      that by careful follow-up of clinical features and simple laboratory tests, such
      as stool microscopic examinations, it is possible to identify patients unlikely
      to respond to initial therapy by 72 hours permitting the start of alternative
      antimicrobial treatment. This may be of great help where stool culture and
      sensitivity facilities for Shigella spp. are not available.

PMID- 7714936
TI  - Impact of chlorination of water in domestic storage tanks on childhood diarrhoea:
      a community trial in the rural areas of Saudi Arabia.
AB  - During the period September 1991 to February 1992 standard chlorination packages
      of calcium hypochloride were provided for the first time to 171 families residing
      in the catchment area of the Sabt-Bany Bishr Primary Health Care Centre in the
      rural areas of the Asir region, south-western Saudi Arabia. The villagers added
      the packages to their home storage water tanks each time they added water from
      the 220 nearby wells. Analysis of the water samples taken from these wells showed
      that all of them were bacteriologically unfit for human use. By the end of the
      study period there were no bacteriologically unfit water samples taken from the
      tanks of the participating families. Children under 5 years of age whose families
      were not using chlorinated water had twice the risk of diarrhoea compared to
      children from the participating families (odds ratio = 1.98, P = 0.047). The use
      of chlorinated water was associated with a 48% reduction in diarrhoea. These
      results indicate that the chlorination of water can be successfully carried out
      locally in rural areas to improve the health of the population.

PMID- 7714937
TI  - Progress in urinary schistosomiasis control measures in Iran.
AB  - During a ten-year field survey from 1980 to 1989, 1518 cases of Schistosoma
      haematobium were detected in Khoozestan province, the only area in south-west
      Iran where urinary schistosomiasis is prevalent. Most of the cases were detected
      by urine examination and a few by bladder biopsies. The incidence of infection
      was 0.653% in 1980, 0.021% in 1988 and 0.042% in 1989. Strict control measures,
      including mass chemotherapy and mollusciciding, were used to help reduce the
      prevalence of urinary schistosomiasis. The 20-29-year-old age group was the most
      infected; there were no sex differences.

PMID- 7714938
TI  - The public health implications of the increasing predominance of Schistosoma
      mansoni in Egypt: a pilot study in the Nile delta.
AB  - Over the past twenty years, Schistosoma mansoni has apparently replaced
      Schistosoma haematobium as the more prevalent species of schistosomiasis in the
      Nile delta. In this paper we show that this change has profound implications for
      public health strategies, in particular the provision and utilization of
      diagnostic and treatment services for the Egyptian rural population, and for
      health education programmes. The processes of providing and seeking treatment for
      the two forms of schistosomiasis are quite distinct as they have different signs
      and symptoms and are diagnosed in stool and urine samples respectively. In two
      Nile delta villages, where S. mansoni has almost completely replaced S.
      haematobium, we found that health services were geared primarily to S.
      haematobium, and hence many cases of S. mansoni remain undiagnosed and untreated.
      One reason for this is that health unit staff and local people lacked detailed
      knowledge of the two forms of schistosomiasis, indicating the need for health
      education.

PMID- 7714940
TI  - Deltamethrin impregnated bednets against Anopheles minimus transmitted malaria in
      Assam, India.
AB  - Of the 20 Anopheles species caught in villages in Sonapur, Assam, only An.
      minimus was incriminated as a malaria vector by finding sporozoites in the
      salivary glands. It was found to be endophagic and endophilic in Assam and
      because its biting peaked after midnight it was a suitable target for insecticide
      impregnated bednets. After the withdrawal of DDT spraying and collecting a year's
      baseline data, deltamethrin impregnated nets were distributed in 3 villages,
      untreated nets were distributed in 6 villages and 3 were held as untreated
      controls. The population of each of these groups of villages was about 1700. The
      nets were well received by the local tribal population. Human landing catches
      with baits unprotected or under partially lifted nets showed that the nets
      provided a high degree of personal protection against all the local species of
      human biting mosquito. In addition, there was evidence for suppression of the An.
      minimus population in a village with treated nets. Malaria was monitored by
      weekly active surveillance in all the villages. In the untreated control villages
      the slide positivity rate and monthly parasite index rose significantly during
      the trial. In the villages with untreated nets, these parameters showed no
      significant change, but in the villages with treated nets they declined
      significantly. On the basis of these results, the widespread distribution of
      impregnated nets was recommended to the state health authorities.

PMID- 7714939
TI  - Nodular form of local hepatic tuberculosis: case report.
AB  - The nodular form of hepatic tuberculosis (TB) is a very uncommon disease
      characterized by coalescing tubercles to form tumour-like tuberculomas or
      abscesses without evidence of extrahepatic tuberculosis. Since 1950, 23 cases of
      isolated nodular TB in the liver have been reported in the world literature. In
      19 of these cases laparotomy was performed and the correct diagnosis was obtained
      only on histologic examination. We report one additional case of multiple
      tuberculous abscesses which were initially diagnosed as hepatic abscesses and at
      intraoperative evaluation were thought to be a liver tumour. The diagnosis was
      made by histological examination with identification of acid-fast bacili.

PMID- 7714942
TI  - Prevalence of transformation zone Chlamydia trachomatis DNA and serum antibodies
      in Tanzanian gynaecological in-patients.
AB  - Chlamydia trachomatis DNA was detected in cervical transformation zone swabs of
      gynaecological in-patients from Tanzania by two different polymerase chain
      reactions (PCR), one targetting the endogenous Chlamydia trachomatis plasmid
      (pCTT1) and the other a chlamydia genus specific rRNA gene. In only 7/131 (5.3%)
      cervical samples specific amplification products were obtained, in 6 cases with
      both PCRs, and in one with the plasmid-PCR alone. A 255 nt sequence was
      determined from the two plasmid-PCR fragments and revealed only one mismatch
      against the prototype sequence. Antibodies against genus specific chlamydia
      antigens were detectable by indirect immunofluorescence with titres > or = 1:256
      in 29.0% (38/131) of all patients and in 50.0% (11/22) of patients with pelvic
      inflammatory disease (P = 0.17). No statistically significant association of
      either chlamydia antibodies or chlamydial DNA with any clinical condition was
      observable.

PMID- 7714941
TI  - A community-based evaluation of eyesight and spectacle use after intracapsular
      cataract extraction in northern India.
AB  - The visual outcome and extent of aphakic spectacle use at community level was
      evaluated in 177 patients who underwent ICCE in peripheral camps. In 16.9%, both
      eyes were operated. The mean age at cataract surgery was 63 years (range 33-82
      years). After surgery, 79.7% had better vision; 72.3% were extremely satisfied
      with the surgical outcome. Of those with improved or similar vision, 81.9% were
      regularly using aphakic spectacles. Free aphakic spectacles after surgery were
      received by 57.6%. Broken spectacles was the most common cause for not using or
      intermittently using spectacles. The major benefits to patients were the ability
      to undertake personal activities, improved mobility and recognition of family
      members, friends and cattle.

PMID- 7714944
TI  - This month in Investigative Urology. Commentary on the use of neural networks in
      clinical urology.

PMID- 7714943
TI  - Single-dose ampicillin/sulbactam versus ceftriaxone as treatment for
      uncomplicated gonorrhoea in a Ugandan STD clinic population with a high
      prevalence of PPNG infection.
AB  - During the period November 1989 to March 1991 a total of 330 patients (269 males
      and 61 females) with signs and symptoms of uncomplicated lower genital tract
      infections with Neisseria gonorrhoeae were treated at a sexually transmitted
      disease clinic in Kampala, Uganda. Patients were randomized for treatment with
      either intramuscular ampicillin/sulbactam (1 g ampicillin/0.5 g sulbactam), plus
      1 g probenecid orally, or ceftriaxone (250 mg). In those cases where N.
      gonorrhoeae was isolated and the patients returned for a follow-up visit, 70/74
      (95%) of the patients treated with ampicillin/sulbactam and 71/72 (99%) of those
      treated with ceftriaxone had favourable clinical outcomes. All 24 patients with
      penicillinase-producing N. gonorrhoeae (PPNG) treated with ampicillin/sulbactam
      had a favourable clinical outcome compared with 95% (20/21) of those with PPNG
      treated with ceftriaxone. The infecting pathogen was eradicated in 65/71 (92%) of
      the evaluable patients treated with ampicillin/sulbactam and in 60/63 (95%) of
      the ceftriaxone group. Both drug regimens were well tolerated and there were no
      reports of adverse drug effects. In summary, in a predominantly male group of
      clinic patients in Kampala, Uganda, ampicillin/sulbactam was as safe and
      effective as ceftriaxone in treating uncomplicated gonococcal infections of the
      lower genital tract caused by either PPNG or non-PPNG strains.

PMID- 7714945
TI  - Options in replacement cystoplasty following radical cystectomy: high hopes or
      successful reality.

PMID- 7714946
TI  - The clinical introduction of a third generation lithotriptor: Modulith SL 20.
AB  - The Modulith SL 20* was designed as a third generation lithotriptor with
      outstanding disintegrative efficacy in vitro, and equipped with a combined
      fluoroscopic and ultrasound localization system integrated in a multifunctional
      table. Its introduction to clinical extracorporeal shock wave lithotripsy took
      place in 3 phases. In phase 1 (49 patients) only in line ultrasound localization
      was possible. The many caliceal stones were adequately disintegrated with
      restricted generator voltage. In phase 2 (81 patients) fluoroscopic localization
      with the virtual focus of an adapted x-ray C-arm unit enabled in situ lithotripsy
      of ureteral stones in 33% of all patients. Phase 3 (549 patients) was
      characterized by additionally increasing the generator voltage to 20 kv. This
      development of the lithotriptor by improving the localization system and shock
      wave energy resulted in the possibility for successful disintegration of stones
      in the entire upper urinary tract (including the complete ureter), decreased
      treatment time (52 to 39 minutes) and an improved efficiency quotient (0.45 to
      0.67). During phase 3 auxiliary measures were performed before lithotripsy in 24%
      of the cases. After 1.8% of the treatments minor or moderate perirenal fluid
      collection or bleeding was detected by routine followup sonography. A 91% stone
      free rate was achieved with only 9.3% curative auxiliary measures after
      extracorporeal shock wave lithotripsy, including a 23% retreatment rate. Thus,
      the Modulith device had a high efficacy quotient compared with other
      lithotriptors.

PMID- 7714947
TI  - Submucosal calculi: endoscopic and intraluminal sonographic diagnosis and
      treatment options.
AB  - After shock wave lithotripsy and endoscopic lithotripsy, occasionally a patient
      has persistent ureteral fragments associated with ureteral obstruction. After
      lithotripsy, stone fragments may be embedded in the ureteral mucosa, and they may
      become completely submucosal and associated with obstruction. Others may be
      hidden in iatrogenic ureteral outpouchings, while still others may be extruded
      from the ureter entirely. We present 20 patients who were referred after previous
      treatment failed to clear fragments or who had residual obstruction. The majority
      of patients had failed endoscopic fragment retrieval or shock wave lithotripsy
      and were referred with ureteral obstruction. All patients were reevaluated by
      repeated upper tract endoscopy with small diameter endoscopes. As an adjunct to
      ureteral endoscopy, a 6F, 20 MHz. ultrasound probe was placed transureterally to
      determine the depth and location of stones. A total of 15 patients in this series
      had hyperechoic foci with shadowing consistent with submucosal or periureteral
      stone fragments. A decision for treatment was based upon the location as noted by
      sonographic and fluoroscopic visualization of intramucosal and submucosal
      fragments. Calculi more than 4 mm. from the lumen were not removed without
      evidence of obstruction. Multiple, small (speckled) fragments embedded in the
      mucosa were often associated with subsequent stricture. Solitary fragments within
      the wall of the ureter could be removed with relief of obstruction. The risk of
      embedding calculi submucosally during lithotripsy should be recognized.
      Submucosal fragments causing obstruction should be removed endoscopically.
      Totally extruded calculi may be left in situ safely.

PMID- 7714948
TI  - Cardiac dysrhythmias related to extracorporeal shock wave lithotripsy using a
      piezoelectric lithotriptor in patients with kidney stones.
AB  - It is well known that, during extracorporeal shock wave lithotripsy (ESWL) for
      kidney stones, shock waves delivered by a spark-gap generator frequently elicit
      cardiac arrhythmias. However, detailed data are lacking concerning the
      arrhythmogenesis of ESWL using a piezoelectric lithotriptor, even though this
      type of machine has generally been considered not to induce cardiac arrhythmia.
      Therefore, the prevalence and nature of cardiac dysrhythmias during piezoelectric
      ESWL were examined in 34 patients with kidney stones in whom cardiac disease
      other than dysrhythmia had been excluded. Each patient underwent 24-hour
      electrocardiographic recording 2 to 3 days before ESWL. On the day of ESWL
      electrocardiography was recorded continuously beginning from 4 hours before until
      the end of the procedure. The relationship between ESWL related dysrhythmia and
      autonomic neural activity was also evaluated by heart rate spectral analysis.
      Piezoelectric ESWL was found to elicit new or worsened tachyarrhythmia
      originating from the atria and/or ventricles in 20 patients (59%) and serious
      bradycardiac arrhythmia in 1. However, piezoelectric ESWL related dysrhythmias
      were not associated with the dysrhythmias in the daily life of the patients.
      Heart rate spectral analysis suggested that changes in autonomic neural activity
      were involved in the mechanism(s) of ESWL related dysrhythmia. Although lethal
      dysrhythmia has not yet occurred at this institution, it is considered that
      patients at risk for life threatening cardiac dysrhythmia should be monitored
      closely even if ESWL for kidney stones is done with a piezoelectric lithotriptor.

PMID- 7714949
TI  - Treatment of renal colic by desmopressin intranasal spray and diclofenac sodium.
AB  - The vasopressin analogue, 1-desamino-8-arginine vasopressin (desmopressin), is a
      potent antidiuretic without the pressor effects of vasopressin. A total of 18
      patients with acute renal colic due to stone disease received 40
      microgramsf1p4mopressin intranasal spray with encouraging results. There was a
      significant decrease in the colic pain intensity from an initial mean visual
      analogue score of 67 +/- 17 mm. to 39 +/- 36 mm. within 30 minutes (p < 0.001).
      Eight patients (44.4%) had complete pain relief within 30 minutes of
      administering intranasal desmopressin spray. Nine of 10 patients who required
      intramuscular diclofenac sodium achieved complete pain relief within another 30
      minutes. In other words, when intranasal desmopressin spray was administered
      before diclofenac sodium, 94.4% of the patients achieved complete pain relief and
      were discharged home. The mechanism of analgesic action of desmopressin in renal
      colic is uncertain. At the peripheral level, desmopressin may alleviate the acute
      renal colic through its potent antidiuretic effect or by relaxing the renal
      pelvic and ureteral smooth muscles. The central analgesic effect of desmopressin
      by stimulating the release of the hypothalamic beta-endorphin is proposed. We
      conclude that intranasal desmopressin spray can be used successfully in the
      treatment of renal colic. It may also replace prostaglandin synthetase inhibitors
      in treating renal colic with the advantage of avoiding the potential side
      effects. Further studies are needed to investigate whether the combination of
      desmopressin with analgesics or spasmolytic drugs offers competitive results
      compared with those achieved by prostaglandin synthetase inhibitors in the
      treatment of renal colic.

PMID- 7714950
TI  - Ureteropelvic junction obstruction with a simultaneous renal calculus: long-term
      followup.
AB  - We reviewed 111 patients who presented with simultaneous renal calculi and a
      ureteropelvic junction obstruction. Of 34 patients with ureteropelvic junction
      obstruction and a coexisting struvite stone 62% had recurrent calculi. The use of
      antibiotics significantly affected the incidence of recurrent struvite calculi.
      In particular, if prolonged prophylactic antibiotics (greater than 3 months) were
      used 15% of the patients had recurrent stones, compared to 90% if only
      perioperative antibiotics (less than 15 days) were used (p < 0.001). Patients
      with ureteropelvic junction obstruction and coexisting nonstruvite calculi were
      treated by either observation alone (53) or metabolic evaluation with appropriate
      intervention (24). Metabolic evaluation of patients with nonstruvite calculi
      revealed that 76% had an identifiable metabolic abnormality, treatment of which
      significantly decreased the incidence of recurrent renal calculi: 17% of the
      patients on interventional therapy had recurrent stones compared to 55% treated
      by observation alone (p < 0.001).

PMID- 7714951
TI  - Long-term renal fate and prognosis after staghorn calculus management.
AB  - We analyzed retrospectively 177 consecutive staghorn calculus patients to
      determine risk factors for ultimate renal deterioration and renal cause specific
      death. Mean followup was 7.7 years. Overall rate of renal deterioration was 28%.
      Renal deterioration was associated more frequently among patients with solitary
      versus nonsolitary kidneys (77% versus 21%, p < 0.001), previous versus initial
      stones (39% versus 14%, p = 0.03), recurrent versus nonrecurrent calculi (39%
      versus 22%, p = 0.07), hypertension versus normotension (50% versus 22%, p =
      0.006), complete versus partial staghorn calculi (34% versus 13%, p = 0.02),
      diversion versus no diversion (58% versus 19%, p < 0.001) and neurogenic bladder
      versus normal voiding (47% versus 21%, p = 0.006), as well as those who refused
      treatment versus treated patients (100% versus 28%, p < 0.001). No patient with
      complete clearance of fragments died of renal related causes compared to 3% of
      those without clearance of fragments and 67% of those who refused treatment (p <
      0.001). Our study suggests that long-term renal preservation in the staghorn
      calculus patient may depend on normal blood pressure, staghorn size, absence of
      diversion or voiding dysfunction, and complete stone eradication.

PMID- 7714952
TI  - Stones.

PMID- 7714953
TI  - Laparoscopic partial nephrectomy: initial experience and comparison to the open
      surgical approach.
AB  - During an 18-month period, 6 laparoscopic partial nephrectomies were attempted, 4
      of which were successful. The surgical technique was modified and improved
      between cases aided by new laparoscopic instrumentation, such as the argon beam
      coagulator and the 7.5 MHz. ultrasonic sector scanning system. In a retrospective
      comparison between laparoscopic and open partial nephrectomy, estimated blood
      loss was 525 ml. for the former versus 708 ml. for the latter procedure. However,
      operating time was more than 2 hours longer with the laparoscopic approach. The
      major advantages of the laparoscopic procedure appear to be a more rapid return
      to full diet, less postoperative pain and less requirement for parenteral
      narcotics. Despite the small size of this series and limited followup data,
      convalescence may be shortened by 4 weeks after laparoscopic partial nephrectomy.
      Patients with benign diseases of the kidney, especially with a duplicated
      collecting system, who require partial nephrectomy may be considered candidates
      for the laparoscopic approach. The advantages to the patient, however, may be
      offset by the technical demands on the surgeon.

PMID- 7714954
TI  - Is ipsilateral adrenalectomy a necessary component of radical nephrectomy?
AB  - Due to the increased use of modern imaging systems during the last few years,
      kidney tumors are often diagnosed at an earlier and less advanced stage. This
      fact implies a reevaluation of the operative technique of radical nephrectomy
      that was recommended 30 years ago. The ipsilateral adrenal involvement during
      radical nephrectomy for renal cell carcinoma is assessed and the necessity of its
      extirpation is discussed. Between September 1987 and September 1993, we performed
      299 radical nephrectomies for renal cell carcinoma and removed 285 ipsilateral
      adrenal glands. Eleven adrenal glands (3.8%) were involved with the kidney tumor
      and 274 (96.2%) were free of disease. In 7 of the adrenal gland involved cases
      (63.6%) the tumor invaded the gland by direct extension from the superior pole of
      the kidney. In the other 4 cases the ipsilateral adrenal gland was affected by a
      metastatic lesion. In all 11 adrenal gland involved cases the tumors were at an
      advanced stage (the lowest was stage pT3N1). Our results led us to recommend
      adrenalectomy during radical nephrectomy only when direct extension of the kidney
      tumor into the gland is suspected (upper pole or large tumors) or when the
      adrenal is the site of a single metastasis. Macroscopically normal adrenal glands
      at radical nephrectomy should not be routinely extirpated. Metastatic renal cell
      carcinoma (not by contiguity) in the ipsilateral adrenal gland should be regarded
      as a stage M+ (distant metastasis) tumor.

PMID- 7714955
TI  - Transurethral ureteroscopic ureterotomy assisted by a prior balloon dilation for
      relieving ureteral strictures.
AB  - We developed a procedure to correct ureteral obstruction that consists of
      transurethral ureteroscopic balloon dilation of the stenotic segment followed by
      a ureteroscopic ureterotomy. Since February 1989 we treated 20 ureters in 19
      patients with upper urinary tract obstruction, with an 85% success rate. Stenosis
      was primary in 4 patients, and secondary to a prior operation in 10, calculi in 4
      and endometriosis in 2. The stenotic segment was pretreated with balloon dilation
      through an 11.5F rigid ureteroscope and then incised using a 12F optical
      ureterotome equipped with a cold knife. Thereafter, a 12F Double-J* catheter was
      left in situ for 6 weeks. Followup ranged from 4 to 55 months (mean 18). In these
      19 patients obstruction resolved completely in 8 (8 ureters) and partially in 8
      (9 ureters). Postoperatively, the obstruction remained unchanged in 2 patients
      and 1 experienced injury to the common iliac artery during the procedure. Our
      findings suggest that this procedure may prove beneficial in treating obstructive
      ureteral diseases.

PMID- 7714956
TI  - Surgical anatomy of the lumbar vessels: implications for retroperitoneal surgery.
AB  - The lumbar vessels in the retroperitoneum must be addressed during many
      urological and vascular procedures. Few studies have assessed the exact pattern
      of the lumbar vasculature, and most anatomical descriptions suggest the presence
      of a generally regular pattern. The number and location of the infrarenal lumbar
      arteries and veins were documented in 102 consecutive retroperitoneal lymph node
      dissections. Anomalies of the renal vessels were also noted. The lumbar arteries
      followed a fairly regular pattern and individual variation occurred mainly in the
      number of lumbar arteries exiting the aorta (range 2 to 4). Great variation
      existed among the lumbar veins. The most common pattern of lumbar arteries (60%
      of the cases) included 3 paired vessels exiting posteriorly at every third of the
      infrarenal aorta and coursing diagonally toward the lumbar foramina. There was
      great variation in the number and location of lumbar veins along the inferior
      vena cava. Commonly 3 lumbar veins entered on the left (44%) and 2 on the right
      (37%) sides. A lumbar vein entering the left renal vein was documented in 43% of
      the cases. Accessory renal arteries were found in 24 cases (24%). The number and
      course of the lumbar vessels are more variable than previously described in the
      medical literature. Knowledge of these anatomical variations is important for
      surgeons operating in the retroperitoneum. Several techniques to maintain control
      of the lumbar vessels are described.

PMID- 7714957
TI  - Bio-fragmentable anastomosis ring in urological surgery involving the
      gastrointestinal tract: early experience and a historical review of mechanical
      intestinal anastomosis.
AB  - We present our experience with use of a bio-fragmentable mechanical device for
      intestinal anastomosis in 14 patients. No anastomotic leakage occurred in our
      patients. The technique was easy to learn and shortened the operating time by at
      least 30 minutes. Our impression is that during time-consuming extensive onco
      urological procedures involving the gastrointestinal tract, the use of such a
      device allows for a shorter operative time to the benefit of the patient and
      surgeon.

PMID- 7714958
TI  - Ureterosigmoidostomy: is it a viable procedure in the age of continent urinary
      diversion and bladder substitution?
AB  - Between January 1977 and June 1985, 63 patients requiring supravesical diversion
      underwent ureterosigmoidostomy with an antireflux technique. Of the patients 49
      had bladder cancer and 14 had other conditions. Two patients died in the
      postoperative period. Postoperatively, all patients were instructed to empty the
      rectum frequently, and received bicarbonate and potassium supplementation. Median
      followup was 41 months (range 3 to 70). Renal function remained stable in 92% of
      the patients. Radiographic deterioration occurred in 23% of the renal units,
      which was severe in 7%. These results indicate that the short and intermediate
      followup results with ureterosigmoidostomy are comparable to those of an ileal
      conduit. The method has the added advantage of being a form of continent
      diversion. We believe that ureterosigmoidostomy remains a viable and convenient
      alternative in select patients with bladder cancer who are not suitable for other
      forms of continent diversion or bladder substitution.

PMID- 7714959
TI  - A simple ileal substitute bladder after radical cystectomy: experience with a
      modification of the Studer pouch.
AB  - Bladder substitution using pouches designed from detubularized bowel is gaining
      widespread acceptance among urologists and their patients. However, few clinical
      reports have described the effectiveness of the orthotopic neobladder fashioned
      from ileum in the manner described by Studer. Since 1988, we have used the Studer
      technique with minor modifications in 20 men who underwent radical
      cystoprostatectomy for transitional cell carcinoma of the bladder. Early
      morbidity from the procedure was minimal, although 2 patients later had
      anastomotic strictures. Significant late complications included low vitamin B12
      levels in 4 patients and persistent hyperchloremia in 1. A total of 18 patients
      achieved diurnal continence but 9 of these had enuresis. Neobladder compliance
      and emptying were satisfactory in the 12 patients evaluated urodynamically. Upper
      tracts remained stable in all patients at a median followup of 24 months (range 9
      to 60). Isolated episodes of bacteriuria occurred in 11 patients but followup
      urine cultures have remained sterile in all continent patients. The Studer ileal
      neobladder is a simple, effective alternative for urine storage, upper tract
      preservation and efficient voiding.

PMID- 7714960
TI  - Reconstruction and diversion.

PMID- 7714961
TI  - Production of soluble virulence factor by Escherichia coli.
AB  - Experimental evidence suggests that adherence is a prerequisite for bacterial
      infection. We demonstrated that transitional cells at the surface of the bladder
      are coated with glycosaminoglycans (proteoglycans and mucus) whose presence
      efficiently decreases bacterial adherence to the mucosa. Exposure of mucus to
      protamine sulfate, a quaternary amine (known to form salts with
      glycosaminoglycans and inactivate them) significantly increases the bacterial
      adherence to the bladder. Investigators have primarily focused on bacterial
      surface factors (that is pili or fimbriae, glycocalix) in relation to the ability
      to adhere. We explored the hypothesis that Escherichia coli produces a soluble
      virulence factor that increases the infection rate in rabbits by promoting
      bacterial adherence to the bladder mucosa. In addition, it was proposed that this
      factor is a quaternary amine similar to protamine. For these studies an in vivo
      bacterial infection assay (which we described previously in rabbits) was used to
      examine E. coli metabolic products (soluble virulence factor) that could promote
      bacterial persistence in the bladder by perturbing mucus (glycosaminoglycans),
      and promote bacterial adherence and virulence. E. coli was grown in human urine
      and a bacterial-free supernatant was collected. Rabbit bladders were then exposed
      to either this supernatant or to the same human urine that was not infected with
      E. coli. Results show a significantly higher bacterial persistence (bacterial
      count) in bladders pretreated with urine containing the E. coli supernatants
      compared to controls pretreated with uninfected urine (p = 0.03). The molecular
      weight of the putative soluble virulence factor is less than 3.5 kD. (p = 0.056)
      based on dialysis studies and binds to heparin agarose affinity chromatography
      matrix, suggesting that it is cationic and capable of adhering to the highly
      anionic bladder mucus (glycosaminoglycans).

PMID- 7714962
TI  - Apparent failure of current intravesical chemotherapy prophylaxis to influence
      the long-term course of superficial transitional cell carcinoma of the bladder.
AB  - During the 4 decades since the first introduction of intravesical chemotherapy,
      3,899 patients were enrolled in 22 randomized prospective controlled studies. Of
      these 22 studies 13 reported a statistically significant benefit of intravesical
      chemotherapy. With varying followup, the reported decrease in the incidence of
      patients with tumor recurrence averaged only 14% (range -3 to +43%).
      Unfortunately, long-term (5-year) studies show no decrease in the incidence of
      recurrent tumor. Maintenance chemotherapy has failed to improve these results and
      data suggest that a single early postoperative instillation may, in fact, be most
      effective. Among 10 studies that include progression data none showed decreased
      tumor progression, and overall among 2,011 randomized patients progression
      occurred in 7.5% of those receiving intravesical chemotherapy and 6.9% of those
      treated by surgery alone. Since intravesical chemotherapy has been demonstrated
      in animal models to be carcinogenic, these data raise the concern that
      intravesical chemotherapy might possibly be carcinogenic in humans. In the
      absence of demonstrated long-term benefit we question the advisability of routine
      prophylactic intravesical chemotherapy.

PMID- 7714963
TI  - Tanagho bladder neck reconstruction in the treatment of adult incontinence.
AB  - We studied the effectiveness of tubularized bladder neck reconstruction in the
      treatment of 8 patients with complex incontinence using urodynamic and clinical
      methods. The patients had undergone Tanagho bladder neck reconstruction within
      the last 10 years. Three of the 8 patients were judged unsuitable for artificial
      sphincter implantation because of severe scarring, and loss of urethral and
      vaginal tissue. There were 7 women with epispadias or severe urethral damage as a
      consequence of obstetrical or gynecological procedures. Five patients underwent 7
      concurrent procedures at the time of bladder neck reconstruction, including
      colposuspension (4), and closure of a fistula involving the bladder neck (1) and
      urethra (1) plus vaginal reconstruction (1). Of 8 patients 5 (63%) were
      completely continent and satisfied, 2 underwent ileal conduit diversion (1
      because of incontinence and 1 refused clean intermittent self-catheterization),
      and 1 is incontinent and awaiting further treatment. The best results were noted
      in patients with a healthy bladder and periurethral tissues. Four of 5 patients
      (80%) deemed potentially suitable for artificial urinary sphincter insertion were
      satisfied compared to only 1 of 3 (33%) unsuitable for artificial urinary
      sphincter insertion. The Tanagho bladder neck reconstruction is a useful addition
      to the procedures that may be used by the reconstructive urological surgeon in
      the treatment of carefully selected patients with complex incontinence,
      particularly in women with epispadias who for various reasons may wish to avoid
      the long-term potential complications of an artificial urinary sphincter.

PMID- 7714964
TI  - A modified Raz bladder neck suspension operation (transvaginal Burch)
AB  - A total of 36 female patients with genuine stress urinary incontinence underwent
      Raz needle suspension with fixation of suspension sutures to the iliopectineal
      ligament (transvaginal Burch procedure). By fixing suspension sutures to the
      iliopectineal ligament we expected to achieve a static suspension independent of
      everyday patient activities. Considering the small number of patients and limited
      followup, our results revealed continence in 80 to 85% of the patients after 3
      years. We believe that fixation of suspension sutures to the iliopectineal
      ligament can favorably influence long-term results of needle suspension in the
      treatment of female stress urinary incontinence.

PMID- 7714965
TI  - Comparison of bladder management complication outcomes in female spinal cord
      injury patients.
AB  - A total of 70 female spinal cord injury patients was retrospectively analyzed for
      outcomes of long-term bladder management. Three groups were defined: 1) 23
      patients on intermittent catheterization, 2) 25 treated by reflex voiding and
      incontinence padding, and 3) 22 with an indwelling catheter. Mean years of using
      the specific bladder management technique were 8.5 +/- 4.7, 15.8 +/- 7.3 and 16.7
      +/- 9.0 for the 3 groups, respectively. All patients were evaluated for long-term
      complications. There were 4 major complications (17%) in the intermittent
      catheterization group, 10 (40%) in the padding group and 58 (greater than 200%)
      in the indwelling catheter group. The aggregate difference in complication rates
      among the 3 group was highly significant (p < 0.00001). Of comparable long-term
      patients (11 to 23 years) there were no major complications among 6 on
      intermittent catheterization, 8 among 14 who use padding and 21 among 9 with an
      indwelling catheter. The differences among the groups remained significant (p <
      0.00001). Additional analyses showed highly significant differences between the
      catheter group and the other 2 groups (intermittent catheterization p = 0.0009
      and padding p = 0.0005), and a difference that approached significance between
      the intermittent catheterization and padding groups (p = 0.085). The results
      strongly support intermittent catheterization as the optimal management of female
      patients following spinal cord injury given that other factors, in particular
      independent hand function or the need for appropriate assistance, are considered.

PMID- 7714967
TI  - Neurogenic bladder.

PMID- 7714966
TI  - A predictive score index for the outcome of associated biofeedback and vaginal
      electrical stimulation in the treatment of female incontinence.
AB  - A group of 64 women with stress incontinence alone (20), urgency incontinence (7)
      and mixed incontinence (37) were treated during 12 sessions, each 20 minutes
      long, during 6 weeks with combined alternating biofeedback and intravaginal
      electrical stimulation. Of the patients 21 had a complete recovery, 20 recovered
      sufficiently to avoid other forms of treatment and 23 failed to respond to the
      treatment. Thus, the overall success rate for this treatment was 64%. Various
      physiological parameters were collected from each patient before the start of the
      treatment sessions. Patient age, estrogen status, detrusor hyperreflexia,
      intravaginal pressure, percent transmission of the abdominal pressure to the
      urethra, degree of intrinsic sphincter deficiency and compliance with therapy
      were significant factors affecting the success of treatment. A statistical
      analysis was performed on these measurements to generate a score index model
      capable of predicting the outcome of a treatment consisting of associated
      biofeedback and electrical stimulation. We present a reliable method for
      distinguishing between patients who will and will not respond to this form of
      treatment. The most significant variables predictive of a good reduction outcome
      are patient age, presence of estrogen, absence of detrusor instability and
      intrinsic sphincter deficiency, low urethral hypermobility and, most of all,
      compliance with treatment.

PMID- 7714968
TI  - Evaluation of penile arteries with color-coded duplex sonography: prevalence and
      possible therapeutic implications of connections between dorsal and cavernous
      arteries in impotent men.
AB  - Penile revascularization for cases of arteriogenic impotence is based on the
      assumption of hemodynamically relevant connections between the dorsal penile and
      cavernous arteries. In 325 clinically impotent patients color-coded duplex
      sonography was performed with the penis flaccid and tumescent after
      intracavernous injection of 10 micrograms prostaglandin E1. We measured peak flow
      velocity, end diastolic flow velocity and resistance in the dorsal arteries, deep
      cavernous arteries and connections perforating the tunica albuginea between the 2
      systems. Of our patients 14% had at least 1 such anastomosis with a peak flow
      velocity exceeding 25 cm. per second after stimulation. Peak flow velocities less
      than 20 cm. per second were noted only in arteriogenically impotent patients,
      while those exceeding 25 cm. per second without later rigid erection occurred
      only in patients with venous occlusive dysfunction and end diastolic flow
      velocity exceeded 5 cm. per second. We conclude that penile revascularization
      should be contemplated only if hemodynamically relevant connections are detected,
      peak flow velocity in the cavernous arteries is less than 20 cm. per second and
      end diastolic flow velocity is less than 5 cm. per second.

PMID- 7714969
TI  - Timing of penile color flow duplex ultrasonography using a triple drug mixture.
AB  - Duplex ultrasonography is an accepted method to assess noninvasively arterial
      inflow to the penis. Optimal pharmacological agents as well as timing of the scan
      and stimulation during the scan continue to be debated. In an effort to achieve a
      more complete smooth muscle relaxation and capture what we perceived was a wide
      variation in interval to maximum arterial velocity, we revised our duplex
      protocol in January 1991. We report on 280 consecutive patients evaluated in this
      manner. Patients received 0.25 or 0.5 cc of a triple drug mixture containing 22.5
      mg./cc papaverine, 0.83 mg./cc phentolamine and 8.33 micrograms/cc prostaglandin
      E1. Scans were performed at 0, 5, 15 and 30 minutes after injection in all
      patients. Any patient not having a full erection at 15 minutes performed private
      self-stimulation while in the standing position for at least 5 minutes before the
      30-minute scan. If we conservatively define normal arterial inflow as a peak
      Doppler velocity of 25 cm. per second or greater in the best artery, only 35% of
      our patients achieved this velocity at 5 minutes. Of the remainder 26% and 22%
      did not reach normal velocity values until 15 and 30 minutes, respectively, after
      the injection. By delaying initial measurements of velocity until 5 minutes,
      could the highest inflow velocity be missed and patients diagnosed incorrectly?
      The group at risk would be those who had good tumescence at 5 minutes and who had
      presumably already decreased the inflow velocities. Of the 280 patients 74 (26%)
      had greater than 10% tumescence at 5 minutes. Only 6 of these 74 patients did not
      reach velocities of 25 cm. per second or more in the best artery at some time
      during their study. In conclusion, our study clearly supports delaying the
      initial scan until 5 minutes, since only 6 of our 280 patients (2.1%) may have
      been incorrectly diagnosed. The study also strongly argues for additional scans
      until 30 minutes and self-stimulation when necessary.

PMID- 7714970
TI  - Combining intracavernous injection and external vacuum as treatment for erectile
      dysfunction.
AB  - We studied the effect of combining intracavernous injection and an external
      vacuum in 10 men with erectile dysfunction who previously failed attempts at
      treatment with either method as single therapy. We measured the length,
      circumference and buckling pressure of the penis at baseline, after applying
      negative pressure (250 mm. Hg for 2 minutes), 15 minutes after intracavernous
      injection of 60 mg. papaverine or 30 micrograms prostaglandin E1 and after
      combining both modalities. No patient achieved adequate rigidity (defined as a
      penile buckle pressure greater than 450 gm.) with single therapy. The mean buckle
      pressure using vacuum alone was 125.0 +/- 53.6 gm. After intracavernous injection
      the mean buckle pressure was 117.0 +/- 38.3 gm. In contrast, all 10 subjects
      responded to combination therapy with a mean buckle pressure of 565.0 +/- 56.8
      gm. (p < 0.0001). After 10 months of followup 3 subjects were still using the
      combination and were satisfied with the erectile response, 1 found that he no
      longer needed the addition of external vacuum after using combination therapy for
      3 months, 1 used the combination for 9 months and then stopped because of an
      intervening acute illness, 1 lost the partner due to death, 2 found combination
      therapy to be too cumbersome and 2 were lost to followup. We conclude that
      external vacuum devices can augment a partial response to intracavernous
      injection and the combination may be an alternative treatment before intrapenile
      prosthesis implantation.

PMID- 7714972
TI  - Impotence.

PMID- 7714971
TI  - Treatment of the intraoperative penile erection with intracavernous
      phenylephrine.
AB  - A total of 23 patients who had an intraoperative penile erection during
      endoscopic or penile surgery underwent intracavernous injection of 200 micrograms
      phenylephrine. Detumescence occurred rapidly in all patients with a single
      injection. Hemodynamic changes consisted of a transient increase in systolic and
      diastolic blood pressures (+9%, p < 0.05) without significant change in pulse
      rate (-5%, p > 0.05). No marked side effect was reported even in elderly
      patients. Intraoperative penile erection, which seems to be more frequent in
      patients younger than 50 years, during general anesthesia with propofol or
      epidural anesthesia, can be treated safely with intracavernous injection of
      phenylephrine.

PMID- 7714973
TI  - Comparison of biothesiometry and neuro-urophysiological investigations for the
      clinical evaluation of patients with erectile dysfunction.
AB  - In the literature the determination of the vibration sensitivity threshold of the
      penile glans by means of biothesiometry has been introduced as a cost-effective
      office test for the evaluation of penile neuropathy in impotent men. At our
      facility we have gained extensive experience with neuro-urophysiological tests
      for the evaluation of penile innervation. These neuro-urophysiological tests have
      the disadvantage of complexity, invasiveness and time consumption. In our study
      both methods were compared in 31 impotent patients. The results showed that
      penile glans biothesiometry yields consistent results when measurements are
      repeated during 1 session. However, no relationship was found between the outcome
      of penile glans biothesiometry and neuro-urophysiological tests of the dorsal
      penile nerve, which is probably due to the fact that vibration is not an adequate
      stimulus to the skin of the penile glans that contains free nerve endings (that
      is pain receptors) only, and hardly any vibration receptors. We conclude that
      biothesiometric investigation of penile glans innervation is unsuited for the
      evaluation of penile innervation and cannot replace neuro-urophysiological tests.

PMID- 7714974
TI  - Preliminary results of a comparative study with intracavernous sodium
      nitroprusside and prostaglandin E1 in patients with erectile dysfunction.
AB  - We compared the effect of intracavernous administration of sodium nitroprusside,
      a nitric oxide donor and, therefore, stimulator of the cyclic guanosine
      monophosphate pathway, with the activity of prostaglandin E1, which is a
      stimulator of the cyclic adenosine monophosphate pathway. To date 105 patients
      with erectile dysfunction have entered the study. As part of the diagnostic
      evaluation every patient received an intracavernous injection of 20 micrograms
      prostaglandin E1 and a second injection of sodium nitroprusside at different
      concentrations (100 micrograms in 10 patients, 300 micrograms in 60 and 400
      micrograms in 35). Sodium nitroprusside at a dose of 100 micrograms was not
      effective for inducing erections. Prostaglandin E1 induced better responses
      overall than sodium nitroprusside at 300 and 400 micrograms (p < 0.001). The
      overall duration of erections was also significantly longer with prostaglandin E1
      (mean 88.5 minutes) than with 300 micrograms sodium nitroprusside (mean 50.8
      minutes, p < 0.001) but did not reach statistical significance compared to 400
      micrograms sodium nitroprusside (mean 42.2 minutes). Side effects were minimal
      with both drugs. Although sodium nitroprusside has several benefits over
      prostaglandin E1 for intracavernous use (such as lower cost, absence of local
      pain and shorter action, allowing detumescence after orgasm and decreasing the
      risk of priapism), prostaglandin E1 still remains the agent of choice for
      intracavernous use.

PMID- 7714975
TI  - Erectile dysfunction.

PMID- 7714976
TI  - The volume of prostate cancer in the biopsy specimen cannot reliably predict the
      quantity of cancer in the radical prostatectomy specimen on an individual basis.
AB  - Previous studies suggest that prostate cancer with a volume of 0.5 ml. or less
      and a Gleason score of less than 7 may be clinically insignificant and may be
      managed with watchful waiting. A proposed method of determining the volume of
      cancer in the prostate gland has been the grade and volume of cancer present in
      the transrectal needle biopsy specimen. Volume of cancer in the biopsy specimen
      as a predictor of volume of cancer in the prostate gland was studied in 130 men
      who underwent radical retropubic prostatectomy for adenocarcinoma. Of the men 46
      (35%) had clinical stage T1c (nonpalpable) disease, while 84 (65%) had clinical
      stage T2 (palpable) disease. Each radical prostatectomy specimen was whole
      mounted and step-sectioned for accurate cancer volume determination. Three
      parameters for measuring volume of cancer in the biopsy specimen (percentage of
      biopsy cores involved, millimeters of cancer per biopsy core and percentage of
      cancer in the biopsy specimen) were determined and compared by Spearman rank
      correlation analysis. The percentage of cancer in the biopsy specimen was
      marginally better than the percentage of cores involved and the millimeters of
      cancer per biopsy core as a predictor of cancer volume in the radical
      prostatectomy specimen. While regression analysis revealed a direct correlation
      between the volume of cancer in the biopsy and radical prostatectomy specimens (r
      = 0.51), there was significant variability in prostate cancer volume for a given
      percentage of cancer in the biopsy specimen since the standard error of the
      estimate was 6.1 ml. Of the 13 patients with 5% or less cancer volume and a
      Gleason score of less than 7 in the biopsy specimen 1 (8%) had a cancer smaller
      than 0.5 ml. in volume in the radical prostatectomy specimen. Therefore, the risk
      of removing clinically insignificant prostate cancer, even when the biopsy
      parameter indicates low volume disease, is less than 10%. Overall, only 3 study
      patients (2.3%) had a prostate cancer volume of less than 0.5 ml. With 97.7% of
      the men having a clinically significant cancer by a volume criterion, it is
      apparent that the majority of clinically insignificant prostate cancers remained
      undetected and untreated. Currently, transrectal needle biopsy does not provide
      adequate information for differentiating between clinically insignificant and
      life threatening prostate cancer on an individual basis.

PMID- 7714977
TI  - Lewis Y antigen as detected by the monoclonal antibody BR96 is expressed strongly
      in prostatic adenocarcinoma.
AB  - We used the monoclonal antibody BR96 to determine the expression of the Lewis Y
      antigen in benign and malignant prostatic tissues. Strong immuno-staining was
      detected within the basal cells of benign glands in 29 of 30 specimens examined.
      In contrast, weak immuno-staining of the secretory (luminal) epithelium was
      detected in only 10 of these same 30 specimens. Moderate to strong immuno
      staining of luminal cells, however, was observed in prostatic intraepithelial
      neoplasia in 15 of 17 specimens. Immuno-staining was detected within the
      malignant cells in all 49 specimens of primary prostatic adenocarcinoma examined.
      We used a semiquantitative technique to compare the extent of immuno-staining
      among well (combined Gleason score less than 6), moderately (combined Gleason
      score 6 to 7) and poorly (combined Gleason score more than 7) differentiated
      tumors as well as metastatic lesions. Poorly differentiated tumors demonstrated
      the greatest extent of immuno-staining compared to moderately and well
      differentiated adenocarcinoma. Strong immuno-staining was also detected within
      the malignant cells in 7 metastatic (5 nodal lesions and 2 bone marrow biopsies)
      tumors. The extent of immuno-staining in the metastatic lesions was similar to
      that observed in the poorly differentiated primary tumors. In summary, the Lewis
      Y antigen, as detected by BR96, is widely expressed within prostatic
      adenocarcinomas. Furthermore, the poorly differentiated as well as metastatic
      lesions frequently demonstrated the highest expression of the Lewis Y antigen.

PMID- 7714979
TI  - Prostate cancer.

PMID- 7714978
TI  - Immediate estrogen or estramustine phosphate therapy versus deferred endocrine
      treatment in nonmetastatic prostate cancer: a randomized multicenter study with
      15 years of followup. The South Sweden Prostate Cancer Study Group.
AB  - From November 1978 to July 1984, 285 men with previously untreated, localized
      prostate cancer were consecutively randomized in an open multicenter study. The
      main objective was to determine if early endocrine treatment prolongs the
      interval to metastasis and/or cancer related or overall survival. Patients were
      randomized to receive either 80 mg. polyestradiol phosphate by intramuscular
      injection every 4 weeks plus 50 micrograms ethinylestradiol 3 times daily or 280
      mg. estramustine phosphate 2 times daily, or for surveillance only but with
      deferred endocrine treatment at progression to metastatic disease. From 1983
      further inclusion into the polyestradiol phosphate plus ethinylestradiol group
      was closed because of a high frequency of cardiovascular complications and
      thereafter 13 patients were instead randomized to a new treatment group with 80
      mg. polyestradiol phosphate only by intramuscular injection every 4 weeks. Mean
      age was 70 years for 228 evaluable patients: 66 in the polyestradiol phosphate
      plus ethinylestradiol group, 74 in the estramustine phosphate group and 88 in the
      deferred treatment group, respectively. Mean followup for 100 patients alive on
      August 31, 1993 was 144 months (range 111 to 180). During the observation period
      51 patients had metastasis. There was no difference in interval to metastasis (p
      = 0.07) among the 3 groups, although there was a tendency for a higher
      probability of metastases in the deferred treatment group. A total of 128
      patients (56%) died during the observation period and prostatic cancer was
      considered to be the cause of death in 46 (20%). There was a significant
      difference (p = 0.03) among the 3 groups in the probability of dying of prostatic
      cancer, with the highest risk in the surveillance group but we found no
      significant difference in overall survival. The relevance of different prognostic
      factors and their interaction with treatment was also evaluated. These analyses
      were applied to the entire patient group as well as to the different subgroups.
      We found that patients with moderately well differentiated cancer (stage greater
      than T0a) who received early treatment with estramustine phosphate had the lowest
      risk of metastases or death from prostatic cancer, while those with well
      differentiated cancer (stage greater than T0a) did best on early polyestradiol
      phosphate plus ethinylestradiol treatment.

PMID- 7714980
TI  - Transperitoneal laparoscopic versus open adrenalectomy for benign
      hyperfunctioning adrenal tumors: a comparative study.
AB  - In our retrospective study we compare the effectiveness and safety of
      transperitoneal laparoscopic versus open adrenalectomy in 40 patients with benign
      hyperfunctioning unilateral adrenal tumors. Patients 1 to 20 underwent open
      adrenalectomy between July 1988 and July 1992, and patients 21 to 40 underwent
      the laparoscopic procedure between September 1992 and January 1994. Student's t
      test for unpaired data was used to compare intraoperative and postoperative
      results, and morbidity observed in the 2 groups. The affected adrenal gland was
      successfully removed in all cases. Mean operative time was significantly longer
      for laparoscopy, although it shortened progressively due to the learning curve
      effect. Blood loss was significantly less with laparoscopy, while only 3 patients
      undergoing open surgery required blood transfusions. Overall invasiveness and
      analgesic requirement were significantly lower with laparoscopy. The intervals to
      oral intake and ambulation, hospital stay and return to preoperative normal
      activity were shorter with laparoscopy. Major complications were noted only in
      open surgery patients. At 3 months all patients in both groups were cured of the
      underlying adrenal disease. We conclude that transperitoneal laparoscopic
      adrenalectomy is equally effective and less invasive than open surgery, and that
      it should be considered the first choice therapy for benign hyperfunctioning
      adrenal tumors.

PMID- 7714981
TI  - Laparoscopic dismembered pyeloplasty: preliminary report.
AB  - As a reconstructive laparoscopic procedure, dismembered pyeloplasty was done in 5
      patients: the laparoscopic procedure was completed in 4 and converted to an open
      operation in 1. Within this series operative time decreased from 390 to 190
      minutes. The main operating time was devoted to laparoscopic suturing of the
      anastomosis. Spreading the renal pelvis by either pulling the sutures
      transcutaneously or with intra-abdominal stay sutures improved visualization and
      facilitated the anastomosis. Mean postoperative hospitalization was 8 days (range
      7 to 10). After a mean followup of 9 months (range 6 to 15) excretory urography
      and renal scintigraphy revealed significant radiographic improvement and no
      obstruction in 4 patients. Compared to open pyeloplasty and endo-pyelotomy,
      laparoscopic pyeloplasty may combine the advantages of open surgery (excision of
      the stenosis and reduction of the renal pelvis) with those of minimally invasive
      surgery (minimal postoperative morbidity), provided the operative time can be
      shortened and the technique simplified.

PMID- 7714982
TI  - Ongoing advances in laparoscopic surgery.

PMID- 7714983
TI  - A new method for the relief of adult phimosis.
AB  - Infantile circumcision is not ordinarily performed in Japan. Adult circumcision
      causes esthetic problems with scarring and color change, especially in Asian
      patients. We report our experience with 10 adults who underwent a new method of
      surgery for correction of phimosis via a longitudinal incision of the prepuce
      along the constricted area ventrally to release constriction, followed by
      transverse closure of the wound; removal of excess skin by pinching at the dorsal
      root of the penis, incising circumferentially except for 2 cm. of ventral skin,
      and closing the dorsal wound. Functional results in all cases were satisfactory
      and preputial constriction was fully relieved. Cosmetic results were superior to
      those of conventional circumcision and dorsal slit methods of adult circumcision
      because contrasting coloration was obscured behind pubic hair and scarring was
      coincidental with or beneath the pubic hairline.

PMID- 7714984
TI  - Ectopic splenic tissue simulating a renal mass.
AB  - A 64-year-old patient who underwent splenectomy presented clinically with ectopic
      splenic tissue simulating a solid renal mass. The splenic origin of the mass was
      assessed by radionuclide spleen scan. Nephrectomy was avoided.

PMID- 7714985
TI  - Diagnosis and management of urethral sarcoidosis.
AB  - We report on a woman with urethral sarcoidosis with obstructive urinary symptoms
      and previously known systemic sarcoidosis. The diagnosis of this rare lesion and
      management are discussed, and the genitourinary manifestations of sarcoidosis are
      reviewed.

PMID- 7714986
TI  - Hyper-dopaminemia may produce an increased outlet resistance of the prostatic
      urethra: a case report of malignant pheochromocytoma.
AB  - We report on a 43-year-old man with difficult urination attributed to malignant
      pheochromocytoma with hyper-dopaminemia. A decrease and increase in the plasma
      dopamine values during the clinical course clearly coincided with improvement and
      deterioration, respectively, in urination difficulty. The prostatic peak pressure
      decreased by 37% when the plasma dopamine value was minimal. Detrusor function
      was normal throughout. Endocrinological and urodynamic studies suggested that
      hyper-dopaminemia produced an increased outlet resistance of the prostatic
      urethra without altering detrusor function. Thus, peripheral dopaminergic systems
      may influence voiding mechanisms, especially those involving the proximal
      urethra.

PMID- 7714987
TI  - Combined chemoradiotherapy for locally advanced squamous cell carcinoma of the
      bulbomembranous urethra: a case report.
AB  - Patients with locally advanced squamous cell carcinoma of the bulbomembranous
      urethra fare poorly whether they undergo surgery or primary radiotherapy.
      Combined chemoradiotherapy has been used with encouraging results in the
      treatment of squamous cell carcinoma of the anal canal and esophagus, and limited
      reports suggest that this management may show promise in the control of squamous
      cell carcinoma of the urethra. We report good results in a man with locally
      advanced squamous cell carcinoma of the bulbomembranous urethra who underwent
      concomitant radiotherapy, mitomycin C and 5-fluorouracil. We encourage the use of
      this regimen in patients with urethral squamous cell carcinoma as well as the
      reporting of results.

PMID- 7714988
TI  - High flow priapism associated with sickle cell disease.
AB  - Priapism associated with sickle cell disease is classically described as a low
      flow state. We report 2 cases of high flow priapism associated with sickle cell
      disease. High flow priapism has previously been reported almost exclusively in
      patients with traumatic rupture of the cavernous artery. Neither of our patients
      had historical or radiographic findings consistent with injury to the penile
      vasculature. One patient was treated unsuccessfully with intracorporeal injection
      of methylene blue and 1 underwent successfully bilateral pudendal artery
      embolization. The pathophysiological mechanism(s) responsible for the production
      of high flow priapism in patients with sickle cell disease is not known.

PMID- 7714989
TI  - Focal inflammation of the corpus cavernosum in a diabetic man due to acute
      occlusion of the cavernous artery.
AB  - Inflammation of the penile corpus cavernosum is an unusual condition most often
      associated with an infectious process. We report on a diabetic man with localized
      inflammation of the corpus cavernosum resulting from acute occlusion of the
      cavernous artery. Diagnosis was made by exclusion and ultimately confirmed by
      penile angiography. Conservative measures led to resolution of this process.

PMID- 7714990
TI  - Verruciform xanthoma: a benign penile growth.
AB  - Verruciform xanthoma is a rare benign lesion. The majority of the cases occur on
      the oral mucosa. However, other sites, particularly the anogenital region, may be
      involved. We report the eleventh case in the literature of verruciform xanthoma
      of the penis. Genital verruciform xanthoma is significant because it can simulate
      verrucous carcinoma or invasive squamous cell carcinoma. Proper diagnosis by
      clinical recognition, adequate but limited biopsy and histopathological
      examination will avoid unnecessarily aggressive surgical procedures. The
      pertinent clinical and histological features of our case are described and the
      literature on penile verruciform xanthoma is reviewed.

PMID- 7714991
TI  - The reversibility of anabolic steroid-induced azoospermia.
AB  - Anabolic steroid associated male infertility is a little known but potentially
      treatable form of drug related infertility. We report on a bodybuilder with a 5
      year history of steroid use who was azoospermic. He underwent successful
      gonadotropin replacement and conception was achieved 3 months after therapy was
      initiated. Important diagnostic and therapeutic considerations in steroid-induced
      infertility are discussed.

PMID- 7714992
TI  - Percutaneous aortic stent placement for life threatening aortic rupture due to
      metastatic germ cell tumor.
AB  - Patients with testicular carcinoma frequently present with advanced disease and
      symptoms resulting from metastatic lesions. We report an unusual case of
      successful emergency management of a massive rupturing aortic pseudoaneurysm
      midway through systemic chemotherapy for stage III germ cell tumor by
      percutaneous trans-luminal placement of an aortic bypass stent-graft. Unstable
      hemorrhage was controlled, allowing our patient to complete chemotherapy and
      undergo elective retroperitoneal lymph node dissection with resection of the
      pseudoaneurysm and residual disease after normalization of tumor markers. Final
      pathological evaluation revealed only fibrosis in the resected tissue. Followup
      angiography demonstrated a patent stent-graft and the patient was without
      evidence of disease 1 year after retroperitoneal lymph node dissection.

PMID- 7714993
TI  - Cutaneous metastasis following laparoscopic pelvic lymphadenectomy for prostatic
      carcinoma.
AB  - A case of implantation metastasis in the abdominal wall following transabdominal
      laparoscopic pelvic lymphadenectomy is reported. A cutaneous nodule was palpated
      at 1 of the laparoscopic ports 6 months after laparoscopic lymphadenectomy in a
      66-year-old patient with stage T3pN1M0, grade 2 adenocarcinoma of the prostate.
      Aspiration cytology confirmed metastatic adenocarcinoma.

PMID- 7714994
TI  - Persistence of mullerian duct derivative syndrome in 2 male patients with
      bilateral cryptorchidism.
AB  - The persistent mullerian duct syndrome represents a rare form of male
      pseudohermaphroditism secondary to anti-mullerian hormone deficiency. We describe
      2 cases of phenotypically male postpubertal patients with a uterus and tubes.
      Both patients presented with bilateral cryptorchidism, 1 was seen for
      gynecomastia and 1 was seen for an abdominal mass that was found to be a
      testicular tumor.

PMID- 7714995
TI  - Severe hemoglobinuria masquerading as gross hematuria following mitral valve
      replacement.
AB  - Gross hemoglobinuria following mitral valve replacement can represent a rare form
      of hemolytic anemia. This condition can masquerade as gross hematuria in the post
      valve replacement patient. It is commonly associated with valvular dysfunction,
      specifically, perivalvular leakage. The leakage may not be apparent on routine
      echocardiography but it may be documented with trans-esophageal echocardiography.

PMID- 7714996
TI  - Delayed hypersensitivity reaction after infusion of nonionic intravenous contrast
      material for an excretory urogram: a case report and review of the literature.
AB  - Delayed adverse reactions to ionic and nonionic intravenous contrast media have
      been reported previously. We report a case in which delayed hypersensitivity to
      iohexol, a nonionic intravenous contrast agent commonly used in excretory
      urography, resulted in a bi-phasic allergic response. This reaction consisted of
      a mild post-infusion episode of urticaria, which preceded and was clinically
      distinct from a moderately severe dermatological eruption. The episode of
      urticaria was self-limited. The dermatological reaction was treated successfully
      with antihistamine therapy.

PMID- 7714997
TI  - Re: Ultrasonic diagnosis of renal cell carcinoma in hemodialysis patients.

PMID- 7714998
TI  - Re: Evaluation of polydimethylsiloxane as an alternative in the endoscopic
      treatment of vesicoureteral reflux.

PMID- 7714999
TI  - Ureteral graft in urological reconstruction: clinical experience and review of
      the literature.
AB  - We report 7 cases in which grafts of ureter were used as tube and patch segments
      in urethral reconstruction and formation of a continent catheterizable stoma. The
      ureteral grafts survived without long-term stricture in all cases. Meticulous
      preparation of the graft and recipient bed is required for success, as previously
      demonstrated experimentally. When available, ureter is an excellent source of
      tissue for urological reconstruction.

PMID- 7715001
TI  - Long-term outcome evaluation of patients undergoing the meatal advancement and
      glanuloplasty procedure.
AB  - A total of 100 consecutive children with distal hypospadias who underwent a
      variation of the Duckett procedure of meatal advancement and glanuloplasty
      between 1985 and 1990 was evaluated for outcome in terms of urinary stream,
      erection, cosmetic appearance and overall parental satisfaction. Minimum interval
      between procedure and reevaluation for this study was 3 years. Parents of 90 of
      the 100 children were surveyed by surgeons via telephone and 89 (99%) expressed a
      high level of satisfaction with the outcome.

PMID- 7715000
TI  - Nonsecretory sigmoid cystoplasty: experimental and clinical results.
AB  - We report the results of experimental and clinical studies in which a de
      epithelialized segment of sigmoid colon was used to cover the bladder dome where
      the mucosa was exposed (auto-augmentation) to increase bladder capacity.
      Experimentally, the technique was performed in 10 healthy female mongrel dogs and
      the intestinal segments established continuity perfectly over the exposed bladder
      mucosa. Histology 30 and 60 days postoperatively showed transitional epithelium
      lining the intestinal segment at the site of implantation. One island of
      intestinal mucosa was found. The technique was performed in 10 patients,
      including 9 with neurogenic bladder secondary to myelomeningocele and 1 with
      posterior urethral valves. Bladder capacity improved in all cases and
      intravesical pressure was reduced. Followup ranged from 6 to 43 months. The
      technique is proposed as a valuable alternative to traditional full-thickness
      patches of the digestive tract and auto-augmentation.

PMID- 7715002
TI  - Functional characteristics of the reconstructed neourethra after island flap
      urethroplasty.
AB  - To test the neourethra objectively in cases judged to be clinical successes after
      transverse island flap hypospadias repair, we analyzed uroflowmetry data (peak
      flow, voided volume and ultrasonically determined post-void residuals) after
      repair. Patients were included if they were old enough to void volitionally and
      flow data were available after fistula or stricture repair. Flow data were then
      plotted on previously published age-dependent nomograms from normal controls. Of
      80 boys available for study 51 required no secondary procedures, 16 subsequently
      underwent fistula repair and 13 had strictures opened. After all primary and
      secondary procedures 55 patients (69%) had peak flows within the normal range and
      25 (31%) had peak flows below the normal range. Of the 51 boys who never had
      fistulas and/or strictures 37 (73%) had normal flows while 18 of 29 (62%) who
      underwent fistula and/or stricture repairs had normal flows (p < 0.05). Residual
      volume was less than 10% of voided volume in 44 of the 51 boys who clinically had
      no problems postoperatively, in 8 of the 13 who had strictures opened and in 15
      of the 16 who underwent fistula repairs. We conclude that the neourethra is
      functionally equivalent to a normal urethra in most boys after transverse flap
      urethroplasty. A majority of boys will have normal flow even after stricture or
      fistula repair.

PMID- 7715004
TI  - Some newer issues in hypospadias repair.

PMID- 7715003
TI  - Buccal mucosal urethral replacement.
AB  - Graft substances, such as skin and bladder mucosa, have been previously used for
      urethral replacement when local epithelial tissue was not available. However,
      these substances have been associated with meatal prolapse, stricture and fistula
      formation. We have used buccal mucosa as a tissue for urethral substitution in
      these situations during the last 8 years. We review our clinical experience in 18
      urethral reconstructions performed for urethral replacement in 4 cases of
      exstrophy/epispadias, 12 complex hypospadias repairs and 2 cases of complex
      bulbar urethral strictures. There have been 5 cases of meatal stenosis (2
      requiring operative revision) but none of meatal eversion. There has also been 1
      urethrocutaneous fistula and 1 mid graft stricture. Mean followup was 27 months
      and minimum followup was 6 months. Histological examination of the buccal mucosal
      graft compared to grafts of skin showed that the full thickness of the dermis or
      lamina propria is thinnest while the native vascular supply is greatest in the
      buccal mucosa. These 2 factors are associated with improved graft take and may
      explain the encouraging clinical results.

PMID- 7715005
TI  - Complete male epispadias: genital reconstruction and achieving continence.
AB  - We report on 15 patients who were primarily treated for complete male epispadias
      at our institution since 1975. Repair of epispadias was performed using a
      modified Young urethroplasty in 13 patients and a Cantwell-Ransley urethroplasty
      in 2. In addition, 2 patients underwent a Cantwell-Ransley urethroplasty with
      chordee repair after a previous Young urethroplasty failed. Bladder capacity
      increased from a mean of 50 cc before repair to 92 cc after urethroplasty. A
      urethrocutaneous fistula developed in 6 cases, including 5 Young repairs and 1
      Cantwell-Ransley. Three fistulas resolved spontaneously and there were no
      urethral strictures. Bladder neck reconstruction was performed in 11 patients.
      Time to initial continence ranged from 21 days to 6 months (mean 3 months)
      postoperatively. All patients attained daytime continence in a mean of 9 months
      (range 21 days to 24 months) after bladder neck reconstruction, including 9 of 11
      (82%) who achieved total day and night continence. Mean followup was 7 years
      (range 1 to 10). Modern treatment of complete male epispadias allows for an
      excellent genital appearance and achievement of urinary continence.

PMID- 7715006
TI  - Correction of retractile concealed penis.
AB  - Several different mechanisms may account for the concealed appearance of the
      penis. A particular type of concealed penis is the retractile penis, due to
      dysgenetic fibrous bands tethering the penis to the prepubic subcutaneous tissue.
      The retractile nature of the concealment can be confirmed by flexion of the hips.
      A simple technique for surgical correction of the retractile penis is described.
      While there are many different methods to correct a concealed penis, proper
      selection of the technique based on understanding of the pathophysiology is
      critical to a successful outcome.

PMID- 7715007
TI  - Subpubic sinus: a remnant of cloaca.
AB  - A 14-month-old girl had purulent discharge from a sinus over the subpubic region
      for 2 weeks. Radiography and voiding cystourethrography revealed a 4.5 cm. long
      fistula extending to the retropubic region without any connection to the lower
      urinary tract. The fistula was excised. Histological findings revealed that the
      fistula had 3 different types of epithelium: stratified squamous, transitional
      and columnar. Clinical and pathological findings indicated that the sinus was
      most likely a remnant of the cloaca.

PMID- 7715008
TI  - Neural network analysis of quantitative histological factors to predict
      pathological stage in clinical stage I nonseminomatous testicular cancer.
AB  - A great deal of controversy exists in staging clinical stage I (CSI)
      nonseminomatous testicular germ cell tumors (NSGCT) because of the difficulty of
      distinguishing true stage I patients from those with occult retroperitoneal or
      distant metastases. The goal of this study was to quantitate primary tumor
      histologic factors and to apply these in a neural network computer analysis to
      determine if more accurate staging could be achieved. All available primary tumor
      histological slides from 93 CSI NSGCT patients were analyzed for vascular
      invasion (VI), lymphatic invasion (LI), tunical invasion (TI) and quantitative
      determination of percentage of the primary tumor composed of embryonal carcinoma
      (%EMB), yolk sac carcinoma (%YS), teratoma (%TER) and seminoma (%SEM). These
      patients had undergone retroperitoneal lymphadenectomy or follow-up such that
      final stage included 55 pathologic stage I and 38 stage II or higher lesions. Two
      investigators were provided identical datasets for neural network analysis; one
      experienced researcher used custom Kohonen and back propagation programs and one
      less experienced researcher used a commercially available program. For each
      experiment, a subset of data was used for training, and subsets were blindly used
      to test the accuracy of the networks. In the custom back propagation network, 86
      of 93 patients were correctly staged for an overall accuracy of 92% (sensitivity
      88%, specificity 96%). Using Neural Ware commercial software 74 of 93 (79.6%)
      were accurately staged when all 7 input variables were used; however, accuracy
      improved from 84.9 to 87.1% when 2, 4 and 5 of the variables were used.
      Quantitative histologic assessment of the primary tumor and neural network
      processing of data may provide clinically useful information in the CSI NSGCT
      population; however, the expertise of the network researcher appears to be
      important, and commercial software in general use may not be superior to standard
      regression analysis. Prospective testing of expert methodology should be
      instituted to confirm its utility.

PMID- 7715009
TI  - Physiological and morphometric studies into the pathophysiology of detrusor
      hyperreflexia in neuropathic patients.
AB  - The in vitro responses of isolated detrusor strips obtained from neuropathic
      patients with neuropathic bladder dysfunction were found to be supersensitive to
      both carbachol [ED50 1.2 x 10(-6) M. versus 2.5 x 10(-6) M. in control strips; p
      < 0.005] and potassium chloride [ED50 41.8 mM. versus 49.3 mM. in control strips,
      p < 0.05]. There were no significant differences in the frequency-response curves
      obtained with intramural nerve stimulation. However, expressed as a percentage of
      the maximal response with carbachol, the maximal responses to intramural nerve
      stimulation in neuropathic strips were reduced [58.3 +/- 21% versus 74.4 +/- 18%
      for control strips; p < 0.005, Student t test]. Morphometric studies revealed a
      lower density of 'presumptive' cholinergic nerves in neuropathic detrusor (1.0 +/
      1.4 x 10(-4) microns -2 compared with 3.2 +/- 1.3 x 10(-4) microns -2 in
      controls, p < 0.05, Mann Whitney U test). The combined physiological and
      morphometric results were in keeping with a state of postjunctional
      supersensitivity of neuropathic detrusor secondary to a partial parasympathetic
      denervation of the smooth muscle. This may be an important factor in the etiology
      of detrusor hyperreflexia. The contractility of neuropathic tissue in response to
      field stimulation was found to be much lower than normal (2.4 +/- 1.5 g./10 mg.
      versus 5.9 +/- 3.0 g./10 mg., p < 0.001; Mann Whitney U test). This reduced
      contractility to neuronal stimulation might be responsible for some of the
      characteristics of bladder dysfunction that are seen in patients with similar
      neurological conditions.

PMID- 7715011
TI  - Characterization of tachykinin NK2 receptors in human urinary bladder.
AB  - Functional and radioligand binding studies with selective agonists and
      antagonists were used to investigate tachykinin receptors in the human bladder.
      Strips of detrusor muscle were contracted by the tachykinins neurokinin A and
      neuropeptide gamma, and by the NK2 receptor selective agonists
      [Lys5,MeLeu9,Nle10]-NKA(4-10) and [Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4- 10), with
      pD2 values 8.2, 8.0, 8.1 and 7.1. [Sar9,Met(O2)11]-SP and senktide were
      ineffective agonists, indicating an absence of NK1 and NK3 receptors. The
      contractile responses to [Lys5,MeLeu9,Nle10]-NKA(4-10) were inhibited
      competitively by the NK2 receptor selective antagonists SR 48968, GR 94800 and
      MDL 29913, with pA2 values 9.1, 8.6 and 7.0. Specific binding of the new NK2
      receptor selective radioligand [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10) was
      saturable to a high affinity site (KD 2.3 nM.). Specific binding was inhibited by
      NK2 receptor agonists and antagonists, but not by NK1 and NK3 analogues, showing
      binding to NK2 receptors only. These data indicate that NK2 receptors may be
      involved in regulation of detrusor contractility in the human bladder.

PMID- 7715010
TI  - Frequent loss of heterozygosity at 11p loci in testicular cancer.
AB  - Deletions of segments of chromosome 11 have been found to be involved in several
      human tumors. Specific deletion of chromosomal band 11p13 has been associated
      with Wilms' tumors and gonadoblastomas. We performed a deletion analysis of 11p
      using 6 polymorphic probes and DNA from 30 testicular malignancies with
      corresponding normal DNA in 19 patients. A cDNA probe (WT 33) was used to
      evaluate the Wilms' tumor suppressor gene (WT1) for loss by gene dosage analysis.
      Results using the polymorphic probes revealed loss of heterozygosity on 11p in
      59% of informative samples, while use of the WT1 probe revealed loss of
      hemizygosity in 27% of the samples. Northern blot analysis of WT1 was performed
      on mRNA from 3 normal and 1 malignant testis, as well as from 4 testicular cancer
      cell lines (TERA 1, TERA 2, HTE and HTH). Northern blot analysis of the normal
      testes revealed the presence of the expected 3.2 and 2.7 kb transcripts. The TERA
      1, TERA 2 and HTH cell lines were found to express only the 3.2 kb transcript and
      at levels only 3.3%, 29% and 2.8% of normal testes. The HTE cell line did not
      express either of the normal transcripts. Our results reveal considerable allelic
      loss at 11p13 and 11p15, suggesting that these loci may harbor one or more tumor
      suppressor genes important in the development of testicular cancer.

PMID- 7715013
TI  - Mosaicism in human epithelium: macroscopic monoclonal patches cover the
      urothelium.
AB  - Previous studies of chimeric animals and human tissues have shown the clonal
      nature of organ development, giving clues as to the normal development of organs
      and also to abnormal developments, such as atheromatous plaques. The clonal
      nature of bladder cancer in female patients has been demonstrated, but little has
      been known of the clonal development of the normal urothelium. Using an X
      chromosome inactivation analysis of cells microdissected from histologic slides
      from the female human bladder, macroscopic urothelial patches of monoclonality
      were detected. These patches are about 120 mm.2 in size, contain about 2 x 10(6)
      cells each and reflect the presence of coherent cellular families composed of
      stem cells and their differentiated derivatives. The large size of these patches
      was surprising when compared with previously reported patch sizes in other organ
      systems. The patches most probably are composed of the descendants of the
      original founder cells, which would suggest that only 200 to 300 cells
      participated in the formation of the urothelium. The limited number of stem
      cells, each giving rise to millions of cells may provide an explanation for the
      "field defect" that is often referred to in the pathogenesis of bladder cancer,
      as different cell patches may possess different predispositions to tumorigenesis.

PMID- 7715012
TI  - Prolongation of kidney graft survival by cyclophosphamide-induced tolerance in
      rats.
AB  - In this study, we have extended a cyclophosphamide (CP)-induced tolerance system
      to kidney transplantation in rats to examine whether or not we can overcome fully
      allogeneic (major histocompatibility complex plus minor histocompatibility)
      antigen barriers in organ transplantation. In the recipient Lewis (LEW, RT1(1))
      rats that were primed intravenously with 4 x 10(8) spleen cells plus 2 x 10(8)
      bone marrow cells from Brown-Norway (BN, RT1n) rats and treated intraperitoneally
      with 100 mg./kg. of cyclophosphamide (CP) 2 days later, the survival of kidney
      allografts, but not skin allografts, from BN was prolonged as compared with that
      in the untreated LEW rats. Some of the kidney allografts survived for more than
      100 days without further immunosuppressants. The tolerant state induced was
      tolerogen specific, and the suppression of tissue damage of the grafted kidney in
      such tolerant rats was also confirmed by the histopathological findings of the
      grafted kidney. These results indicate that considerable levels of tolerance can
      be induced, at least in organ transplantation, across fully allogeneic antigen
      barriers in rats by a CP-induced tolerance system. We believe that the present
      study is the first step in applying our CP-induced tolerance system using skin
      grafting in the murine model to clinical organ transplantation.

PMID- 7715015
TI  - Immunotherapy of an experimental adenocarcinoma of the prostate.
AB  - We have developed and tested a fractionated, purified and deproteinized emulsion
      of a mycobacterial cell wall (MCW) and report on a controlled study of this
      compound in the treatment of the experimental R3327-H adenocarcinoma of the
      prostate. The intraperitoneal route of administration was found ineffective at
      the weekly dose of 500 micrograms. The intratumoral administration of 1000
      micrograms of MCW exhibited significant antitumor activity. Tumors larger than
      2.2 cm.3 in volume showed evidence of temporary regression, but no cures were
      recorded in these animals. Complete tumor regression was found in 50% of the rats
      with tumor volumes less than 2.2 cm.3 at the onset of treatment. The animals in
      this group not responding initially were treated with a second 3-week course of
      MCW which resulted in complete tumor regression in one-half of the animals, for a
      total cure rate, in the smaller tumor cohort, of 75%. Mycobacterial cell wall is
      an effective biological response modifier in the Dunning R3327-H adenocarcinoma
      of the prostate in Copenhagen rats. Additional studies to elucidate the effect of
      the compound in relation to dose and tumor volume are underway.

PMID- 7715016
TI  - p53 gene mutation in recurrent superficial bladder cancer.
AB  - Surgical specimens from 30 patients with transitional cell carcinoma of the
      bladder were examined for the presence of mutation of the p53 tumor suppressor
      gene using polymerase chain reaction-single strand conformation polymorphism (PCR
      SSCP) analysis. All of the specimens were superficial, low grade cancer, and 10
      patients had recurrences during an observation period of 24 months following the
      initial surgical treatment. Among the 30 patients with superficial bladder
      cancer, 4 were found to have the mutated p53 gene and 3 of them had recurrences,
      which involved either invasive or high grade tumors. Two of these recurrent
      tumors with the p53 gene mutation showed identical mutations with those primary
      tumors, whereas the other one did not have the same mutation. The data suggest
      that bladder cancers with a mutation of the p53 gene have a greater probability
      of poor prognosis than those which do not, even if the primary lesion was a
      superficial, low grade tumor. Therefore, the presence of the p53 gene mutation
      may provide important clues to the factors involved in bladder cancer.

PMID- 7715014
TI  - Age-dependent alterations in beta-adrenergic responsiveness of rat detrusor
      smooth muscle.
AB  - The relaxant effects of norepinephrine (NE, 10(-7) to 10(-4) M.) and
      isoproterenol (ISO, 10(-9) to 10(-4) M.) on maximal KCl-induced tonic
      contractions and the relaxant effects of ISO on contractions induced by
      electrical field stimulation (EFS) were measured in detrusor muscle strips
      obtained from 22-25 day, 90-95 day and 22-month-old male Fischer 344 rats. The
      maximum relaxant response to NE and ISO on KCl-induced tonic contractions
      decreased significantly with increasing age. The ED50 values for ISO, but not NE,
      increased with age. The maximum relaxant response to ISO on EFS-induced
      contractions also was reduced significantly in the old bladders. The relaxation
      effects of forskolin (10(-6) to 3 x 10(-5) M.), dibutyryl cyclic AMP (DBcAMP, 10(
      4) to 3 x 10(-3) M.) and cholera toxin (10 micrograms/ml.) were examined on
      maximal KCl-induced contractions of the muscle strips obtained from the three age
      groups. The relaxant responses to forskolin decreased significantly with
      increasing age, whereas DBcAMP relaxed the muscle strips from the three age
      groups equally. Cholera toxin (10 micrograms) attenuated KCl-induced phasic
      contractions, and this effect was impaired in the aged rat detrusor. The density
      of beta-adrenergic receptors, as determined by radioligand binding with
      [125I]iodopindolol ([125I]-PIN) decreased with increasing age. These data
      demonstrate an age-related decrease in the responsiveness of the bladder detrusor
      to beta-adrenergic stimulation that may be related to the decreased density of
      beta-adrenergic receptors and decreased cyclic AMP (cAMP) production.

PMID- 7715017
TI  - Evidence for the presence of abnormal proteins in the urine of recurrent stone
      formers.
AB  - Two-thirds of matrix of all urinary stones consists of proteins. Despite intense
      research, their relationship to calculogenesis remains controversial. In an
      attempt to study excretion of proteins in stone formers, their urinary profiles
      were analyzed and compared with those of healthy subjects. Two-dimensional gel
      electrophoresis was employed to obtain high resolution separation of proteins.
      The urine of patients with histories of idiopathic calcium oxalate (CaOx) calculi
      contained 7 unique proteins, and 2 others that appeared to be overexpressed.
      Except for alpha 1-acid glycoprotein, the remaining 8 proteins are previously
      unknown constituents of urine with molecular weights of approximately 43, 39.5,
      29, 26, 25.5, 26.5, 27 and 18.5 kD. Their isoelectric points range from 5.5 to
      8.0. Coelectrophoresis of pooled urinary proteins of male and female stone
      formers disclosed that all 9 proteins had identical charges and molecular
      weights, regardless of the donors' sex. Analyses of urines of idiopathic
      recurrent CaOx stone formers who had no radiologically detectable calculi also
      revealed the presence of these proteins. This excludes the possibility that the
      proteins might be a consequence of abrasion of urothelial lining by the
      developing stone(s). Recently defective Tamm-Horsfall mucoprotein (THM) has been
      implicated in urinary stone formation. Coelectrophoresis of pooled urinary
      proteins of healthy subjects and stone formers denoted that it had an identical
      charge and molecular weight in both groups. This suggested that stone formation
      could not be ascribed to a difference in composition of THM. Whether this is
      attributable to a dissimilar amino acid sequence of this mucoprotein, remains to
      be probed.

PMID- 7715018
TI  - Diphtheria in Russia a reminder of risk.

PMID- 7715019
TI  - Scientists stress biodiversity--human health links.

PMID- 7715020
TI  - Cancer cells' immortality may prove their undoing.

PMID- 7715021
TI  - From the Centers for Disease Control and Prevention. Diphtheria epidemic--New
      Independent States of the former Soviet Union, 1990-1994.

PMID- 7715022
TI  - From the Centers for Disease Control and Prevention. Diphtheria acquired by U.S.
      citizens in the Russian Federation and Ukraine--1994.

PMID- 7715023
TI  - From the Centers for Disease Control and Prevention. Vaccination coverage of 2
      year-old children--United States, January-March, 1994.

PMID- 7715024
TI  - From the Centers for Disease Control and Prevention. Licensure of Varicella Virus
      Vaccine, Live.

PMID- 7715025
TI  - Sex and gender bias in illustrations in anatomy and physical diagnosis texts.

PMID- 7715026
TI  - Sex and gender bias in illustrations in anatomy and physical diagnosis texts.

PMID- 7715027
TI  - Sex and gender bias in illustrations in anatomy and physical diagnosis texts.

PMID- 7715029
TI  - Sex and gender bias in illustrations in anatomy and physical diagnosis texts.

PMID- 7715028
TI  - Sex and gender bias in illustrations in anatomy and physical diagnosis texts.

PMID- 7715030
TI  - Sex and gender bias in illustrations in anatomy and physical diagnosis texts.

PMID- 7715031
TI  - Sex and gender bias in illustrations in anatomy and physical diagnosis texts.

PMID- 7715032
TI  - Sex and gender bias in illustrations in anatomy and physical diagnosis texts.

PMID- 7715033
TI  - Sex and gender bias in illustrations in anatomy and physical diagnosis texts.

PMID- 7715034
TI  - Quality of care and mortality in pediatric intensive care units.

PMID- 7715035
TI  - Quality of care and mortality in pediatric intensive care units.

PMID- 7715036
TI  - Aerosolized surfactant in sepsis-induced adult respiratory distress syndrome.

PMID- 7715037
TI  - Tuberculosis transmission in methadone maintenance programs.

PMID- 7715038
TI  - A randomized clinical trial of active compression-decompression CPR vs standard
      CPR in out-of-hospital cardiac arrest in two cities.
AB  - OBJECTIVE: To compare the effectiveness of active compression-decompression (ACD)
      cardiopulmonary resuscitation (CPR) with a handheld suction device vs standard
      manual CPR in victims of out-of-hospital cardiopulmonary arrest. DESIGN:
      Prospective randomized clinical trial with crossover group design. SETTING:
      Emergency medical services (EMS) of a large (San Francisco) and medium-sized
      (Fresno) city in California. PATIENTS: All normothermic adult victims of out-of
      hospital, nontraumatic cardiac arrest on whom CPR was performed by first
      responders. INTERVENTION: Patients were randomized to receive either standard
      manual CPR according to American Heart Association guidelines or ACD CPR, on
      first-responder contact. MAIN OUTCOME MEASURES: Return of spontaneous
      circulation, admission to the intensive care unit, survival to hospital
      discharge, and neurological function at hospital discharge. RESULTS: The ACD
      group (n = 117 in Fresno; n = 297 in San Francisco) and standard group (n = 136
      in Fresno; n = 310 in San Francisco) were similar with regard to demographic and
      prognostic variables, such as age, witnessed arrest and bystander CPR frequency,
      and initial cardiac rhythm. Average interval from 911 call activation to EMS
      responder arrival was 6.4 minutes in Fresno and 4.0 minutes in San Francisco. In
      Fresno, there was no difference between the ACD group and standard CPR group in
      return of spontaneous circulation (17% vs 20%; P = .68), hospital admission (16%
      vs 20%; P = .56), hospital discharge (5% vs 7%; P = .64), or cerebral performance
      category score at discharge (1.5 vs 1.6; P = .90). Similarly, in San Francisco
      there was no difference between the ACD group and standard CPR group in return of
      spontaneous circulation (19% vs 21%; P = .65), hospital admission (13.5% vs
      14.5%; P = .79), hospital discharge (4.7% vs 5.5%; P = .80), or cerebral
      performance category score at discharge (2.2 vs 2.6; P = .31). There was no
      increase in significant complications associated with the use of ACD CPR.
      CONCLUSION: There was no improvement in outcome with ACD CPR in out-of-hospital
      cardiac arrest in these two cities. Differences in study design, demographics,
      EMS systems, response intervals, training, and technique performance may
      contribute to the lack of improvement in initial resuscitation with ACD CPR
      compared with previous studies. Future research needs to control these variables
      to determine the reason for these differences in outcome.

PMID- 7715039
TI  - Plasma concentration of lipoprotein(a) and the risk of future stroke.
AB  - OBJECTIVE: To assess prospectively the risk of future stroke associated with
      baseline concentration of lipoprotein(a), abbreviated Lp(a). DESIGN: Nested case
      control study using baseline plasma samples. SETTING: Men in the Physicians'
      Health Study. PARTICIPANTS: A cohort of 14,916 male physicians with no prior
      history of stroke, transient ischemic attack, or myocardial infarction provided
      plasma samples at baseline and were followed prospectively for 7.5 years. Samples
      from 198 physicians who subsequently developed stroke (155 thromboembolic, 35
      hemorrhagic, eight indeterminate) were analyzed for Lp(a) concentration together
      with paired controls, matched for age and smoking habit. MAIN OUTCOME MEASURE:
      Fatal and nonfatal stroke. RESULTS: Median Lp(a) concentration (8.88 mg/dL [0.23
      mmol/L] vs 8.55 mg/dL [0.22 mmol/L]), P = .69) and overall distributions of Lp(a)
      (P = .54) were similar at baseline in men who did and did not develop future
      stroke. In analyses controlling for age, smoking status, blood pressure, obesity,
      and the presence of diabetes, the relative risks (RRs) associated with baseline
      Lp(a) concentration exceeding the 25th, 50th, 75th, 90th, and 95th percentiles of
      the control distribution were 1.26, 0.99, 1.06, 0.90, and 1.03 (all P values
      nonsignificant). There was likewise no association in analyses limited to
      thromboembolic events. For example, among subjects with baseline Lp(a) values
      exceeding the 95th percentile of the control distribution, the RR of future
      thromboembolic stroke was 1.01 (P = .9). No evidence of association between Lp(a)
      and stroke risk was found in analyses limited to individuals with
      hypercholesterolemia. CONCLUSIONS: Among nearly 15,000 predominantly white,
      healthy, middle-aged men followed in the Physicians' Health Study for a period of
      7.5 years, we found no evidence of association between baseline plasma
      concentration of Lp(a) and future risk of total or thromboembolic stroke.

PMID- 7715040
TI  - Evaluation of a rapid bedside assay for detection of serum cardiac troponin T.
AB  - OBJECTIVE: To evaluate a rapid, qualitative, bedside immunoassay for cardiac
      specific troponin T (cTnT) using a handheld device containing monoclonal
      antibodies. DESIGN: Comparison of rapid cTnT assay with clinical standard for
      diagnosis of myocardial infarction (MI). SETTING: Tertiary care university
      medical center. PATIENTS: A cohort of 100 patients admitted for evaluation of
      chest pain who had sufficient blood samples at presentation for measurement of
      creatine kinase, creatine kinase MB fraction, and rapid cTnT as well as adequate
      clinical data to establish the diagnosis of MI. INTERVENTION: None; treating
      physicians were blinded to rapid cTnT results. MAIN OUTCOME MEASURES: Sensitivity
      and specificity of rapid cTnT assay for MI; likelihood ratios of positive and
      negative rapid cTnT assay results; relative risk (RR) for serious cardiac events
      with positive rapid cTnT assay result on admission. RESULTS: Sensitivity of the
      rapid cTnT assay increased from 33% within 2 hours from the onset of chest pain
      to 86% after 8 hours (P < .001); specificity ranged from 86% to 100% during the
      same time intervals. The odds of an MI increased sixfold with a positive assay
      result within 2 hours of chest pain and decreased sixfold with a negative assay
      result after 8 hours. The RR for experiencing death or nonfatal MI was 6.8 for
      patients presenting with a positive rapid cTnT assay. CONCLUSIONS: The rapid cTnT
      assay is a simple, efficient test that for the first time provides clinicians
      with a useful laboratory tool for point-of-care evaluation of patients with chest
      pain.

PMID- 7715042
TI  - Wegener's granulomatosis.

PMID- 7715041
TI  - Informed consent in emergency research. Consensus statement from the Coalition
      Conference of Acute Resuscitation and Critical Care Researchers.
AB  - OBJECTIVE: A coalition conference of acute resuscitation researchers was held to
      discuss the feasibility of applying current federal research regulations
      regarding informed consent to the emergency setting. This article presents
      consensus recommendations for regulatory changes for consent in emergency
      research. PARTICIPANTS: Representatives from the Society for Academic Emergency
      Medicine and the American Heart Association identified several professional
      organizations as stakeholders in this issue, including research, clinical,
      bioethics, legal, and patient advocacy groups. The Office for Protection From
      Research Risks (OPRR), the Food And Drug Administration (FDA), and staff from
      specific legislative offices were also invited to observe. Forty-three
      participants attended, including representatives from 12 professional
      organizations, five medical institutions, and the FDA and OPRR. This was a closed
      meeting. Participants were self-funded or sponsored by their professional
      organizations. EVIDENCE: Before the meeting, a draft of a position statement was
      developed by the conference organizers based on the current literature and
      discussions with experts in the field. This draft, copies of the current federal
      research regulations, and supporting articles were distributed before the
      conference. CONSENSUS PROCESS: Participants rotated through moderated discussion
      sessions to comment on subsections of the draft. Following discussion, a working
      draft was developed and distributed to each participant and represented
      organizational board for final review. All comments were considered in the final
      version of the document. CONCLUSIONS: We believe there are circumstances when it
      is not feasible to obtain prospective or proxy consent for enrollment into an
      emergency research protocol. In these circumstances, patients are vulnerable, not
      only to research risks, but also to being denied potentially beneficial therapy
      when there is no known effective treatment for their life-threatening condition.
      We offer recommendations that should be met when the critical nature of the
      illness or injury or the need to apply an investigational therapy rapidly
      precludes prospective consent for participation in emergency research.

PMID- 7715043
TI  - Users' guides to the medical literature. VII. How to use a clinical decision
      analysis. A. Are the results of the study valid? Evidence-Based Medicine Working
      Group.

PMID- 7715044
TI  - The accuracy of drug information from pharmaceutical sales representatives.
AB  - OBJECTIVE: To provide quantitative data about the accuracy of the information
      about drugs presented to physicians by pharmaceutical sales representatives.
      DESIGN: One hundred six statements about drugs made during 13 presentations by
      pharmaceutical representatives were analyzed for accuracy. Statements were rated
      inaccurate if they contradicted the 1993 Physicians' Desk Reference or material
      quoted or handed out by the sales representative. SETTING: University teaching
      hospital. RESULTS: Twelve (11%) of 106 statements about drugs were inaccurate.
      All 12 inaccurate statements were favorable toward the promoted drug, whereas 39
      (49%) of 79 accurate statements were favorable (P = .005). None of 15 statements
      about competitors' drugs were favorable, but all were accurate, significantly P <
      .001) differing from statements about promoted drugs. In a survey of 27
      physicians who attended these presentations, seven (26%) recalled any false
      statement made by a pharmaceutical representative, and 10 (37%) said information
      from the representatives influenced the way they prescribed drugs. CONCLUSIONS:
      Eleven percent of the statements made by pharmaceutical representatives about
      drugs contradicted information readily available to them. Physicians generally
      failed to recognize the inaccurate statements.

PMID- 7715045
TI  - Plungers and polemics. Active compression-decompression CPR and federal policy.

PMID- 7715047
TI  - Longevity requires policy revolution.

PMID- 7715048
TI  - Gerontology researchers sharpen focus but face more complex challenges as 21st
      century looms.

PMID- 7715049
TI  - From the Institute of Medicine.

PMID- 7715046
TI  - Research in emergency situations. The role of deferred consent.

PMID- 7715050
TI  - From the Centers for Disease Control and Prevention. Human rabies--Alabama,
      Tennessee, and Texas, 1994.

PMID- 7715051
TI  - Cholesterol and coronary heart disease risk in elderly patients.

PMID- 7715052
TI  - Cholesterol and coronary heart disease risk in elderly patients.

PMID- 7715053
TI  - Smoking, alcohol, and neuromuscular function in older women.

PMID- 7715054
TI  - Catheterization and mortality in elderly patients with acute myocardial
      infarction.

PMID- 7715055
TI  - Catheterization and mortality in elderly patients with acute myocardial
      infarction.

PMID- 7715056
TI  - Catheterization and mortality in elderly patients with acute myocardial
      infarction.

PMID- 7715057
TI  - Smoking, alcohol, and neuromuscular function in older women.

PMID- 7715058
TI  - The effects of exercise on falls in elderly patients. A preplanned meta-analysis
      of the FICSIT Trials. Frailty and Injuries: Cooperative Studies of Intervention
      Techniques.
AB  - OBJECTIVE: To determine if short-term exercise reduces falls and fall-related
      injuries in the elderly. DESIGN: A preplanned meta-analysis of the seven Frailty
      and Injuries: Cooperative Studies of Intervention Techniques (FICSIT)-
      independent, randomized, controlled clinical trials that assessed intervention
      efficacy in reducing falls and frailty in elderly patients. All included an
      exercise component for 10 to 36 weeks. Fall and injury follow-up was obtained for
      up to 2 to 4 years. SETTING: Two nursing home and five community-dwelling (three
      health maintenance organizations) sites. Six were group and center based; one was
      conducted at home. PARTICIPANTS: Numbers of participants ranged from 100 to 1323
      per study. Subjects were mostly ambulatory and cognitively intact, with minimum
      ages of 60 to 75 years, although some studies required additional deficits, such
      as functionally dependent in two or more activities of daily living, balance
      deficits or lower extremity weakness, or high risk of falling. INTERVENTIONS:
      Exercise components varied across studies in character, duration, frequency, and
      intensity. Training was performed in one area or more of endurance, flexibility,
      balance platform, Tai Chi (dynamic balance), and resistance. Several treatment
      arms included additional nonexercise components, such as behavioral components,
      medication changes, education, functional activity, or nutritional supplements.
      MAIN OUTCOME MEASURES: Time to each fall (fall-related injury) by self-report
      and/or medical records. RESULTS: Using the Andersen-Gill extension of the Cox
      model that allows multiple fall outcomes per patient, the adjusted fall incidence
      ratio for treatment arms including general exercise was 0.90 (95% confidence
      limits [CL], 0.81, 0.99) and for those including balance was 0.83 (95% CL, 0.70,
      0.98). No exercise component was significant for injurious falls, but power was
      low to detect this outcome. CONCLUSIONS: Treatments including exercise for
      elderly adults reduce the risk of falls.

PMID- 7715059
TI  - Shared risk factors for falls, incontinence, and functional dependence. Unifying
      the approach to geriatric syndromes.
AB  - OBJECTIVE: To determine whether a set of factors representing impairments in
      multiple areas could be identified that predisposes to falling, incontinence, and
      functional dependence. DESIGN: Population-based cohort with a 1-year follow-up.
      SETTING: General community. PARTICIPANTS: A total of 927 New Haven, Conn,
      residents, aged 72 years and older who completed the baseline and 1-year
      interviews. MAIN OUTCOME MEASURES: At least one episode of urinary incontinence
      per week, at least two falls during the follow-up year, and dependence on human
      help for one or more basic activities of daily living. RESULTS: At 1 year,
      urinary incontinence was reported by 16%, at least two falls by 10%, and
      functional dependence by 20% of participants. The four independent predisposing
      factors for the outcomes of incontinence, falling, and functional dependence
      included slow timed chair stands (lower extremity impairment), decreased arm
      strength (upper extremity impairment), decreased vision and hearing (sensory
      impairment), and either a high anxiety or depression score (affective
      impairment). There was a significant increase in each of incontinence, falling,
      and functional dependence as the number of these predisposing factors increased.
      For example, the proportion of participants experiencing functional dependence
      doubled (7% to 14% to 28% to 60%) (chi 2 = 119.8; P < .001) as the number of
      predisposing factors increased from zero to one to two at least three.
      CONCLUSIONS: Our findings suggest that predisposition to geriatric syndromes and
      functional dependence may result when impairments in multiple domains compromise
      compensatory ability. It may be possible to restore compensatory ability and
      prevent or delay the onset of several geriatric syndromes and, perhaps,
      functional dependence by modifying a shared set of predisposing factors. Perhaps
      it is time to take a more unified approach to the geriatric syndromes and
      functional dependence.

PMID- 7715060
TI  - Age-specific incidence of Alzheimer's disease in a community population.
AB  - OBJECTIVE: To determine age-specific incidence rates of clinically diagnosed
      Alzheimer's disease. DESIGN: Cohort, followed a mean of 4.3 years. SETTING: East
      Boston, Mass. PARTICIPANTS: Of 2313 persons aged 65 years and older who were
      initially free of Alzheimer's disease, 1601 participated in the ascertainment of
      incident disease (80% of survivors), 409 declined participation, and 303 died
      before the end of the follow-up period. A stratified sample of 642 persons
      received detailed clinical evaluation. OUTCOME MEASURE: Diagnosis of new probable
      Alzheimer's disease through structured clinical evaluation including neurologic,
      neuropsychological, and psychiatric examination. Community incidence rates were
      computed by 5-year age groups, adjusted for gender, single year of age, length of
      follow-up interval, and sampling design. RESULTS: The estimated annual incidence
      of Alzheimer's disease in the population was 0.6% (95% confidence interval [CI],
      0.3% to 0.9%) for persons aged 65 to 69 years, 1.0% (95% CI, 0.6% to 1.4%) for
      persons aged 70 to 74 years, 2.0% (95% CI, 1.3% to 2.7%) for persons aged 75 to
      79 years, 3.3% (95% CI, 2.2% to 4.4%) for persons aged 80 to 84 years, and 8.4%
      (95% CI, 3.7% to 13.1%) for persons aged 85 years and older. CONCLUSIONS: The
      incidence of Alzheimer's disease is substantial and is approximately 14 times
      higher among persons older than 85 years compared with those between 65 and 69
      years of age.

PMID- 7715061
TI  - Alzheimer and vascular dementias and driving. A prospective road and laboratory
      study.
AB  - OBJECTIVE: To characterize on-the-road, behind-the-wheel driving abilities and
      related laboratory performances of subjects with mild Alzheimer's disease (AD)
      and vascular dementia. DESIGN: Prospective, experimental study involving two mild
      dementia and three age and health control groups. Road test reliability and
      validity were assessed. SETTING: Greater western Los Angeles. Subjects were
      enrolled from the community by referral and from the Veterans Affairs dementia
      and diabetes clinics. PARTICIPANTS: Eighty-seven driving subjects were enrolled;
      83 completed the study. A sample of eligible dementia clinic subjects consisting
      of 15 mild AD patients met National Institute of Neurological and Communicative
      Disorders and Stroke-Alzheimer's Disease and Related Disorders Association
      probable AD criteria, while 12 met Diagnostic and Statistical Manual of Mental
      Disorders, Revised Third Edition and Hachinski diagnostic criteria for multi
      infarct dementia (vascular dementia). Clinic control subjects consisted of 15 age
      matched patients with diabetes and without a history of stroke or dementia.
      Community controls consisted of 26 healthy, age-matched, older subjects (> 60
      years) and 16 young subjects (20 to 35 years). MAIN OUTCOME MEASURES: Drive score
      from the Sepulveda (Calif) road test and laboratory measures of attention,
      perception, and memory. RESULTS: The drive scores in the mild AD group (mean,
      22.1; SD, 3.8) and in the vascular dementia group (mean, 24.0; SD, 7.8) differed
      significantly (P < .001 studentized range test) from the drive scores in the
      diabetic control group (mean, 31.5; SD, 3.9), the older control group (mean,
      32.6; SD, 2.8), and the young control group (mean, 33.6; SD, 3.2). Drive score
      among the three control groups did not vary significantly. Short-term memory
      (Sternberg), visual tracking, and Folstein Mini-Mental State Examination scores
      correlated best with drive score, with a cumulative R2 of 0.68. Drive score and
      number of collisions and moving violations per 1000 miles driven were negatively
      correlated (r = -0.38; P < .02). CONCLUSIONS: Based on this study, type and
      degree of cognitive impairment are better predictors of driving skills than age
      or medical diagnosis per se. Specific testing protocols for drivers with
      potential cognitive impairment may detect unsafe drivers more effectively than
      using age or medical diagnosis alone as criteria for license restriction or
      revocation.

PMID- 7715062
TI  - Predictors of successful prompted voiding among incontinent nursing home
      residents.
AB  - OBJECTIVE: To develop a simple, noninvasive assessment strategy that will enable
      nursing home staff to identify incontinent residents who respond well to prompted
      voiding. DESIGN: Incontinent nursing home residents underwent an extensive
      clinical and functional assessment and then 7 days of prompted voiding. Data from
      the assessment and the first 3 days of prompted voiding were used to predict
      responsiveness to the intervention. SETTING: Seven nursing homes. PATIENTS: A
      cohort of 191 incontinent, long-stay nursing home residents who passed a simple
      behavioral screen (able to state their name or reliably point to one of two named
      objects). INTERVENTION: Prompted voiding was carried out by trained research
      nurse's aides from 7 AM to 7 PM for 7 days. The intervention was maintained in
      responsive residents 5 days per week for an additional 9 weeks. MAIN OUTCOME
      MEASURES: Physical checks for wetness were done by research staff hourly from 7
      AM to 7 PM for 3 days in a baseline condition, during days 5 through 7 of the 7
      day prompted voiding intervention, and for 3 days at the end of 9 weeks of
      prompted voiding in the responsive group. Outcome measures were percentage of
      checks wet and response to prompted voiding, with "responders" defined as
      residents with an average of one or fewer wet episode per day on days 5 through 7
      of prompted voiding. RESULTS: Seventy-eight (41%) of the residents were
      responders. Their wet percentage went from 26.7% to 6.4% at the end of 1 week and
      was maintained at 9.6% after 9 weeks of prompted voiding. The best predictors of
      responsiveness were the wet percentage and the appropriate toileting percentage
      during the first 3 days of prompted voiding, the self-care subscale score of the
      Multidimensional Observational Scale for the Elderly, and the ability to ambulate
      without human assistance. The best sensitivity and specificity in identifying
      responders was achieved when either the wet percentage was lower than 20% or the
      appropriate toileting percentage was higher than 66% during the first 3 days of
      prompted voiding (sensitivity, 87%; specificity, 69%). Those residents falsely
      identified as responders by these criteria still had a 46% relative reduction in
      wetness. CONCLUSIONS: A substantial proportion of nursing home residents respond
      well to prompted voiding. The most responsive residents can be easily identified
      using data collected during a 3-day trial of the intervention. The assessment
      strategy is consistent with federal guidelines and could be used to facilitate
      quality control by assessing changes in percentage of wetness from the expected
      norm.

PMID- 7715066
TI  - The story of ethics: narrative as a means for ethical understanding and action.

PMID- 7715065
TI  - The science of the art of geriatric medicine.

PMID- 7715064
TI  - Improving the quality of long-term care.
AB  - Quality of long-term care can be improved by changing the strategies used to
      monitor it. Nursing home care has been the subject of intensive regulations,
      while it has been neglected by physicians. Newer forms of long-term care are
      coming under stricter oversight, which may stifle the innovations they offer.
      Greater but different attention is needed: more creativity can be fostered with
      better accountability by emphasizing long-term care outcomes. It is unrealistic
      to require that long-term care patients will improve; good outcomes are defined
      as doing as well as or better than expected. The Minimum Data Set for nursing
      homes offers a mechanism to generate data on many pertinent outcomes. An outcomes
      focus would encourage more collective action by the various parties involved in
      providing long-term care, including physicians. Clinicians are reluctant to
      assume responsibility for outcomes they feel unable to strongly influence, but
      they must recognize that part of their role is to engender cooperation from the
      myriad participants in long-term care, including patients and their families.
      Better-quality long-term care may cost more, but it may be possible to use less
      expensive personnel more creatively if current regulations are modified. Managed
      care arrangements offer one vehicle for reorganizing care and could provide the
      appropriate incentives to make positive changes. However, they could also lead to
      minimalist strategies. Accountability for realistic outcomes can provide the
      needed countervailing regulatory pressure.

PMID- 7715063
TI  - Left ventricular diastolic filling performance in older male athletes.
AB  - OBJECTIVE: To determine whether older men who have undergone intensive endurance
      training over many years demonstrate less age-associated impairment of early
      diastolic left ventricular (LV) filling performance than their sedentary peers.
      DESIGN: Cross-sectional prospective study. SETTING: Community-dwelling research
      volunteers. PARTICIPANTS: Sixteen older competitive male endurance athletes aged
      52 through 76 years and 17 young (< 40 years) and 23 older (52 through 76 years)
      sedentary control subjects from the Baltimore Longitudinal Study of Aging.
      INTERVENTION: All subjects underwent resting Doppler echocardiography and
      determination of maximal aerobic capacity (VO2max) during graded treadmill
      exercise. Doppler echocardiographic studies were interpreted without knowledge of
      the subject's age or exercise habits. MAIN OUTCOME MEASURES: Doppler-derived
      measures of LV diastolic filling performance: peak early (E) filling velocity,
      peak late (A) filling velocity, ratio of peak E to peak A velocities (E/A), and
      atrial filling fraction. RESULTS: Older athletes demonstrated higher VO2max (47
      +/- 6 mL/kg per minute [mean +/- SD]) than either the young controls (41 +/- 7
      mL/kg per minute) or older controls (30 +/- 7 mL/kg per minute) (P < .05) as
      evidence of their superior conditioning status. However, peak E diastolic LV
      filling velocity was higher in young controls (79 +/- 17 cm/s) than in older
      athletes (56 +/- 15 cm/s) or older controls (68 +/- 18 cm/s) (P < .001). This age
      difference persisted after normalizing peak E velocity for mitral stroke volume.
      Peak E/A ratio and atrial filling fraction were also similar in older athletes
      (1.2 +/- 0.5 and 0.41 +/- 0.1, respectively) and older controls (1.1 +/- 0.4 and
      0.41 +/- 0.1, respectively), and differed significantly from corresponding values
      of 1.7 +/- 0.4 and 0.33 +/- 0.1 in young controls (P < .001 and P < .05,
      respectively). By multiple regression analysis, age but not treadmill VO2max was
      a significant predictor of peak E velocity, peak A velocity, peak E/A ratio, and
      atrial filling fraction. CONCLUSION: Older men with a long history of intensive
      endurance training demonstrate impaired early diastolic LV filling similar to
      that of their sedentary peers. Thus, impairment of early diastolic filling
      appears to be intrinsic to normative aging and not secondary to the reduction in
      aerobic capacity that accompanies the aging process.

PMID- 7715067
TI  - Teaching ethical thinking and behavior to medical students.

PMID- 7715068
TI  - Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the
      Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994.

PMID- 7715069
TI  - Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and
      Clonorchis sinensis).

PMID- 7715070
TI  - Infection with Helicobacter pylori.

PMID- 7715071
TI  - Infection with schistosomes (Schistosoma haematobium, Schistosoma mansoni and
      Schistosoma japonicum).

PMID- 7715072
TI  - [Analysis of T cell subsets in autoimmune hemolytic anemia patients].
AB  - To clarify a role of immunoregulatory T cells in the pathophysiology of
      autoimmune hemolytic anemia (AIHA), we investigated T cell subsets in the
      peripheral blood of 15 patients with AIHA by two color analysis using flow
      cytometry. Consequently both CD4+ cells and CD4+CD45RA+ cells decreased in
      proportion, irrespective of the disease activity (active or remission phase).
      CD4+CD45RA+ cells are regarded as naive T cells. Incidentally the ratio of
      CD45RA+ cells in CD4+ cells also fell in the low level in active phase, but it
      recovered to the normal ratio in remission. On the other hand, CD8+ cells and
      CD8+ +S6F1+ cells that may represent activated cytotoxic T lymphocytes increased
      in active phase and then both entered the normal range in remission. These
      findings suggest that AIHA could be caused partly by the alternative balance of
      CD4+CD45RA+ cells probably constituting a member of IRT and moreover by the
      activation of CTL.

PMID- 7715074
TI  - [Initiation of hematopoietic recovery by recombinant human granulocyte-macrophage
      colony-stimulating factor in a case of severe aplastic anemia induced by gold
      salt].
AB  - A 65-year-old female with severe aplastic anemia induced by gold salt, whose
      hematopoietic recovery was initiated by rhGM-CSF therapy, was reported. The
      patient has been given a total of 500 mg of gold-sodium thiomalate for treatment
      of her rheumatoid arthritis. Two months after the final administration of it, she
      was admitted to our hospital with complaints of palpitation and shortness of
      breath. The hemogulobin was 5.9 g/dl, the platelet count was 0.5 x
      10(4)/microliter, and the leukocyte count was 800/microliters with 19%
      neutrophils. Her bone marrow showed aplasia, and both of Ham and sugar-water
      tests were positive. Three times of bolus-methylprednisolone treatment, with or
      without methenolone acetate, resulted in no definite improvement of peripheral
      pancytopenia and marrow aplasia. Subsequent subcutaneous rhGM-CSF, 300 micrograms
      daily for 28 days with oral prednisolone 5 mg and methenolone acetate 40 mg
      daily, initiated hematopoietic recovery of all three cell lineages in both
      peripheral blood and bone marrow. The same doses of prednisolone and methenolone
      acetate were continued after rhGM-CSF administration, and three months later
      peripheral cytopenia and positive Ham and sugar-water tests disappeared
      completely.

PMID- 7715073
TI  - [Hematologic improvement by alpha-interferon in a case of the 5q- syndrome with
      basophilia and eosinophilia].
AB  - An 82-year-old female was diagnosed as having 5q- syndrome accompanied by
      basophilia, eosinophilia and thrombocytosis. Since cytogenetic abnormalities
      other than 5q- were also detected, she was considered to be type B of 5q-
      syndrome. According to the FAB classification a diagnosis of refractory anemia
      with excess of blasts (RAEB) was made. She was treated with recombinant
      interferon alpha 2b, because peripheral blood findings resembled those of chronic
      myelogenous leukemia. Interferon was effective, and resulted in disappearance of
      peripheral blasts, normalization of platelet numbers, and improvement of
      basophilia. These changes were interferon-dependent. After 1 year, cytogenetic
      studies revealed that about 2/3 of metaphases showed normal karyotype. Twenty
      months after diagnosis, myeloid blastic crisis occurred and eventually the
      patient died. However, treatment with interferon in this case might support the
      usefulness of the drugs for this kind of disease.

PMID- 7715075
TI  - [Acute lymphoblastic leukemia accompanied by severe hypercalcemia; successful
      treatment with bisphosphonate].
AB  - A 62-year-old woman was admitted to the hospital because of bone pain. Laboratory
      data showed blasts in the peripheral blood, hypercalcemia (corrected calcium 15.1
      mg/dl) and an increased level of parathyroid hormone related-protein (PTHrP).
      Bone marrow aspiration revealed increased lymphoblasts (96.5%), indicating acute
      lymphoblastic leukemia (ALL, L1). Subsequent radiological examination disclosed
      bone infiltration of ALL. Although the hypercalcemia was successfully treated
      with bisphosphonate, the PTHrP level remained high. After chemotherapy, the
      blasts in the peripheral blood disappeared and the PTHrP level normalized. We
      hypothesize that in the present case the production of PTHrP by lymphoblasts
      resulted in the hypercalcemic state. Although ALL is rarely accompanied by
      hypercalcemia, this case might help us to understand the relationship between ALL
      and hypercalcemia.

PMID- 7715076
TI  - [Artificial insemination using the husband's frozen sperm in a patient with
      chronic myelogenous leukemia after bone marrow transplantation].
AB  - A 37-year-old man with chronic myelogenous leukemia (CML) was scheduled to
      receive a bone marrow allograft from an HLA-matching sibling. He was married
      without children, and desired to have a child in the future. Sperm was collected
      before transplantation and frozen for preservation. Induction therapy performed
      using 8 mg/kg of busulfan, 120 mg/kg of cyclophosphamide, splenic irradiation
      (4.5Gy), and total body irradiation (10Gy), and then allogenic bone marrow
      transplantation (BMT) was carried out. His post-transplantation course was
      uneventful and cyclosporin therapy was finished on day 187. The Philadelphia
      chromosome disappeared on day 20 after BMT and PCR analysis was negative for the
      bcr/abl rearrangement, suggesting the possibility of cure. Accordingly,
      artificial insemination was attempted using the frozen sperm. His wife became
      pregnant after the 4th attempt and a healthy baby was delivered. Transplantation
      recipients often become sterile because they receive ultra-high doses of
      chemotherapy and irradiation. However, it is still possible to have children if
      sperm or ova are preserved prior to transplantation. This is thought to improve
      the quality of life after BMT.

PMID- 7715077
TI  - [Ischemic hepatitis due to anthracycline-induced cardiac insufficiency in a
      patient with acute myelocytic leukemia (M0)].
AB  - A 25 year-old woman diagnosed as acute myelocytic leukemia (M0) suffered a fourth
      relapse in February 1992 at which time she already had anthracycline-induced
      cardiac dysfunction. Although remission was induced by low dose cytosine
      arabinoside and etoposide combined with pirarubicin, she developed acute heart
      failure followed by extreme elevation of transaminases level and DIC. Abdominal
      echography and CT revealed small round lesions in the liver. We diagnosed this
      episode as ischemic hepatitis because of the following clinical findings;
      serological markers of virus hepatitis were negative, hypotension and reduced
      blood flow to the liver were seen, and both transaminases and LDH were markedly
      elevated. Dobutamin and oxygen inhalation were started, her liver function
      returned to almost normal levels 8 days later.

PMID- 7715078
TI  - [Hypoplastic leukemia achieved long-term remission with low-dose cytosine
      arabinoside].
AB  - A 74-year-old woman was admitted in October 1988 with anemia and leukocytopenia.
      Hematologic investigations established a diagnosis of hypoplastic acute leukemia.
      She received a low dose of cytosine arabinoside (LDAC: 10 mg/m2 every 12 hours)
      subcutaneously for 21 days and achieved complete remission (CR) one month later.
      After one course of LDAC of 14 days, she received LDAC of 21 days every 5 to 6
      months as maintenance therapy till April 1993. She has been in remission for 6
      years. Intensification therapy with LDAC every 5 to 6 months might be useful in
      maintaining remission for hypoplastic acute leukemia.

PMID- 7715079
TI  - [von Recklinghausen's disease complicated by macroglobulinemia, malignant
      schwannoma and pheochromocytoma].
AB  - We reported a case of von Recklinghausen's disease complicated by
      macroglobulinemia, malignant Schwannoma and pheochromocytoma. A 43-year-old male
      patient who was diagnosed as von Recklinghausen's disease developed abdominal
      masses at 5 years after the adrenalectomy for pheochromocytoma. Computed
      tomography showed multiple heterogeneous tumors in abdominal cavity. Histological
      examination of resected tumor was compatible with malignant Schwannoma. At the
      same time, peripheral blood and bone marrow smears showed a large number of
      plasmacytoid lymphocytes. Immunoelectrophoresis revealed M-protein of IgM, kappa
      type. He was also diagnosed of coexistence with macroglobulinemia. The
      chemotherapeutic protocols used were not effective against both malignant
      Schwannoma and macroglobulinemia. The present case is a rare case of von
      Recklinghausen's disease associated with triple neoplasms.

PMID- 7715080
TI  - [Analysis of chronic graft-versus-host disease after unrelated-donor bone marrow
      transplantation. Kanazawa University Bone Marrow Transplant Team].
AB  - Six patients with hematologic diseases who received bone marrow from an unrelated
      donor (URD) from 1992 through 1993 and survived for more than 100 days after bone
      marrow transplantation (BMT) were assessed for the incidence, time of onset, and
      extent of chronic graft-versus-host disease (cGVHD). Five patients (83%)
      developed cGVHD, compared with 41% of a control group consisting of 34 patients
      who received bone marrow from a related donor during the same period. In 4 (80%)
      of the 5 patients, cGVHD occurred within 70 days after BMT. This early occurrence
      of cGVHD was observed in only 7% of the control group (P = 0.006). cGVHD tended
      to involve more organs in the URD-BMT patients than in the control group. In two
      patients with cGVHD, an allele mismatch in HLA-DRB1 gene between the patients and
      donor was disclosed by DNA typing. These findings indicate that it is important
      to strengthen post-transplant immunosuppression, to initiate screening tests from
      the early post-transplant period, and to select a suitable donor matched with HLA
      DRB1 alleles for the prevention of cGVHD in the URD-BMT patients.

PMID- 7715084
TI  - [Angiocentric lymphoma associated with anemia secondary to parvovirus B19
      infection].
AB  - A 50-year-old woman was admitted to our hospital in May 1993 because of papules,
      cervical lymphadenopathy and interstitial pneumonia. Oxygen inhalation and pulse
      therapy of corticosteroid were started. A biopsy of the left inguinal lymphnode
      showed T zone enlargement and marked vascularization with polymorphous atypical
      lymphoblasts, consistent with angiocentric lymphoma (immunohistochemically T cell
      type). In situ hybridization with EBER-1 did not show association of EB virus.
      She was subsequently treated with ProMACE-CytaBOM successfully, but anemia had
      progressed before that treatment showing a reticulocyte count 0/1000, LDH 870
      U/l, positive direct Coombs test. Bone marrow aspiration revealed red cell
      aplasia and the existence of giant pronormoblasts. The hemoglobin dropped to the
      level of 4.7 g/dl, requiring anabolic steroid and frequent blood transfusion.
      Parvovirus B19-specific antibodies were negative initially by western blot assay,
      but IgM antibody appeared after 35 days and IgG after 71 days. In August anemia
      improved following a reticulocyte burst and recovery of bone marrow
      erythroblasts. This patient is the first reported case of angiocentric lymphoma
      complicated with severe anemia, perhaps resulting from autoimmune hemolytic
      process and parvovirus B19 infection.

PMID- 7715082
TI  - [Minimally differentiated hypoplastic leukemia].
AB  - Sixty-seven years-old female, who was an atomic bomb survivor in Hiroshima, was
      pointed out as having leukopenia and anemia in 1991. She was referred to Tsukuba
      University Hospital in June 1992. Her peripheral blood count showed pancytopenia-
      2,600/microliters WBC, 10.5 g/dl hemoglobin, and 80,000/microliters platelets- at
      that time. BM biopsy revealed hypoplastic marrow and increased peroxidase
      negative blasts (32.8%). Surface marker analysis of the blasts showed a feature
      of CD2+ CD33+ CD34+ CD13+ CD3-. Electronmicroscopically, myeloperoxidase was
      positive. She was diagnosed as having hypoplastic leukemia of which the blasts
      had a feature of AML-M0 by FAB-group. After 6 months' silent period, her
      pancytopenia became profound. We successfully reduced the blasts by BAM therapy.
      However, she died of bacterial pneumonia during the myelosuppressive state. This
      is a case of minimally differentiated hypoplastic AML.

PMID- 7715081
TI  - [MMIP chemotherapy for the treatment of the relapsed and refractory non-Hodgkin's
      lymphoma].
AB  - For salvage chemotherapy, 30 cases of relapsed or refractory non-Hodgkin's
      lymphoma (NHL) were treated with MMIP regimen (mitoxantrone 15 mg/m2,
      methotrexate 400 mg/m2, and ifosfamide 2 g/m2 intravenously in day 1,
      respectively, and prednisolone 20 mg/m2 orally from day 1 to 5). The overall
      complete response rate (CR rate) was 20% and the median survival duration was 153
      days. In patients with favorable performance status (PS), the CR rate and
      survival duration were 30% and 407 days, respectively. These results were almost
      equivalent to previously proposed salvage regimens. The overall disease free
      survival rate of CR cases at 4 years was 62%, which was excellent as compared
      with the other salvage regimens. Five of 8 (62.5%) patients previously treated
      with etoposide-non-containing regimens achieved CR, and the CR rate was
      significantly superior to that of patients previously treated with etoposide
      containing ones. These results indicate that MMIP is a useful salvage regimen for
      relapsed or refractory NHL, while it seems to be difficult to salvage patients
      previously treated with etoposide-containing regimens.

PMID- 7715085
TI  - [Hematological remission of primary myelofibrosis with antiphospholipid antibody
      following treatment of azathioprine].
AB  - A 46-years-old woman was admitted with purpura, nasal bleeding, gum bleeding,
      gross hematuria, cerebral hemorrhage, and cerebral infarction. The data of her
      peripheral blood were as follows: WBC 17,500/microliters, Hb 5.1 g/dl, PLT 0.3 x
      10(4)/microliters, LDH 924 IU/l. Primary myelofibrosis was diagnosed because of
      bone marrow fibrosis and extramedullary hematopoiesis of the spleen. Furthermore,
      she revealed marked thrombocytopenia and no response to platelet transfusion, so
      association of idiopathic thrombocytopenic purpura (ITP) was considered. Though
      she was treated with high dose predonisolone, high dose gamma-globulin, and
      splenectomy, no hematological improvement was achieved. Administration of
      azathioprine (100 mg/day) was begun and 2 weeks later, her white blood cell count
      was approximately 10,000/microliters, the platelet count 2.0 x 10(4)/microliters,
      and no bleeding focus was found. Four weeks later, her hemoglobin content was
      13.0 g/dl without blood transfusion. The diagnosis of antiphospholipid syndrome,
      rather than ITP, was made because of anticardiolipin-beta 2GPI complex antibody
      and cerebral infarction. It is interesting that immunosuppressant was effective
      both in primary myelofibrosis and in antiphospholipid syndrome.

PMID- 7715083
TI  - [Association of chronic neutrophilic leukemia and myeloma with fibrillar
      inclusions in granulocytes].
AB  - A 57 year-old-female was incidentally found to have leukocytosis in September
      1988. Physical examination revealed anemia and marked hepatosplenomegaly. Her WBC
      count was 33,400/microliters with 95% mature neutrophils showing toxic granules.
      Her neutrophil alkaline phosphatase score was 482, and serum VB12 14,600 pg/ml.
      Serum immunoglobulin concentrations were 582 mg/dl for IgG, 3,628 mg/dl for IgA
      and 48 mg/dl for IgM. IgA was determined as monoclonal origin of lambda type.
      Bone marrow aspiration revealed a hypercellular marrow with active
      granulocytopoiesis and increased plasma cells. Cytogenetic study revealed normal
      karyotype. The bcr rearrangement was negative for bone marrow cells. An
      electronmicroscopy demonstrated fibrillar inclusions in granulocytes. We
      diagnosed this case as a chronic neutrophilic leukemia (CNL) associated with
      multiple myeloma. She was treated with a course of low dose busulfan without
      beneficial response. She was admitted for development of huge subcutaneous
      hematoma of left waist in October 1990. Laboratory findings were: Hb 7.0 g/dl,
      WBC 55, 300/microliters, Platelets 3.3 x 10(4)/microliters, and IgA 6,607 mg/dl.
      She required frequent transfusions. She died of pneumonia in July 1991. The
      peculiar fibrillar inclusions with CNL has not been reported so far. The origin
      and significance of such structure remains uncertain.

PMID- 7715087
TI  - [An autopsy care of hemophagocytic syndrome associated with miliary
      tuberculosis].
AB  - A 56-year-old female with chronic renal failure secondary to diabetic
      glomerulosclerosis was hospitalized and had a fluminant clinical course with
      pancytopenia, abnormal liver function tests, and coagulopathy. Bone marrow
      aspirate findings were typical of reactive hemophagocytosis. The patient died
      after 21 days of hospitalization and autopsy findings showed disseminated miliary
      tuberculosis. To our knowledge, only eight cases of miliary tuberculosis with
      bone marrow hemophagocytosis have previously been described. The presence of
      reactive hemophagocytosis requires a prompt and thorough search for treatable
      infections.

PMID- 7715086
TI  - [Induction and maintenance therapy in all-trans retinoic acid with relapsed acute
      promyelocytic leukemia].
AB  - We reported a 17-year-old girl with relapsed acute promyelocytic leukemia (APL)
      who achieved complete remission and has been received maintenance therapy with
      all-trans retinoic acid (ATRA). The patient was diagnosed as APL in 1986. The
      ANLL 861 protocol of the Children's Cancer and Leukemia Study Group induced
      complete remission, and the chemotherapy was discontinued in 1989. However, she
      suffered a relapse with APL in 1991 and begun receiving ATRA (30 mg/m2/day)
      therapy because of disseminated intravascular coagulation. Bleeding tendency was
      discontinued by day 5. During the treatment, the white blood cell count increased
      markedly to 35,510 per microliters on 15th day, however she achieved complete
      remission morphologically on day 18. After informed consent was obtained from the
      family, she has been given ATRA orally for more than three years at the time of
      this report. The pharmacokinetics examination (ATRA 20 mg/m2 single per os) was
      performed 12 and 22 months after the induction therapy. The each peak plasma
      level of ATRA was 89 and 149 ng/ml. The concentration of ATRA has yet reached a
      level despite the continuous ATRA therapy. We considered that it may be useful to
      monitor plasma levels of ATRA during the treatment.

PMID- 7715088
TI  - [Bilateral ankle ulcers associated with hydroxyurea therapy for chronic
      myelogenous leukemia].
AB  - Bilateral ankle skin ulcers developed in a 61-year-old man in the chronic phase
      of chronic myelogenous leukemia receiving hydroxyurea therapy. The circulating
      immune complex (anti-C3d antibody) was high in this case, but vasculitis was not
      observed in the pathological findings of biopsied skin materials. This
      association has been reported in patients who had chronic myelogenous leukemia or
      other myeloproliferative disorders and were treated with hydroxyurea. It is
      likely that skin ulcers are caused by hydroxyurea.

PMID- 7715089
TI  - [Extramedullary relapse in childhood acute lymphoblastic leukemia: experience at
      the Kyushu Yamaguchi Children's Cancer Study Group].
AB  - Since October 1984, children with acute lymphoblastic leukemia (ALL) were treated
      with six protocols of the Kyushu-Yamaguchi Children's Cancer Study Group
      (KYCCSG). We reviewed cases in whom the first relapse sites of ALL were CNS,
      testis and ovary. Between October 1984 and July 1993, 302 children with ALL were
      registered. Ten children (3.3%) developed CNS-L. After treatment for CNS-L, four
      cases were alive, however one of them has had several episodes of CNS-L.
      Testicular relapse occurred in 8 boys and three of them are alive. One girl
      developed ovarian and uterine involvement 7 months after completion of treatment
      and she survived after intensive chemotherapy for an additional 3 years. Before
      September 1990, children with ALL received 18Gy cranial irradiation in standard
      risk group and 24Gy in high risk group. Since October 1990, children with ALL
      received no cranial irradiation in low risk group, 15Gy in intermediate risk
      group and 18Gy in high risk group. Incidence of CNS-L has not increased in
      children treated with protocols, in which cranial irradiation was reduced.

PMID- 7715090
TI  - [Treatment for elderly patients with acute non-lymphocytic leukemia].
AB  - A retrospective analysis was performed on forty nine elderly (34 males and 15
      females) patients aged 65 years or more (median age 73, range 65-82) with acute
      non-lymphocytic leukemia (ANLL). Patients were studied to examine factors
      according to age group (65-69 years, 70-74, 75-79 and 80 or over), respectively.
      Patients were treated with either low dose Ara-C therapy or BHAC-DMP therapy
      according of the choice of their attending physicians. Complete remission (CR)
      was obtained in 20 of 49 patients (43%), and in 6 of 14 patients (43%) aged 65
      69, in 8 of 18 (44%) aged 70-74, in 5 of 12 (42%) aged 75-79 years and in 1 of 3
      (33%) aged 80 or over, respectively. The median survivals of these groups were
      263, 298, 260, 168.5 and 38.5 days, respectively. Multivariate analysis revealed
      that the achievement of CR was associated with normal karyotype, and serum GOT
      level < or = 30 mu/ml and GPT < or = 40 mu/ml. Prolonged survival was related to
      the achievement of CR. The results indicated that liver function before
      chemotherapy was an important prognostic factor.

PMID- 7715091
TI  - [Clinical characteristics and poor outcomes in patients with de novo AML with
      trilineage myelodysplasia].
AB  - De novo AML with trilineage myelodysplasia (AML/TMDS) is reported to account for
      10-15% of de novo AML and respond poorly to conventional intensive chemotherapy,
      In our series, 12 (25%) of 48 patients with de novo AML were diagnosed as
      AML/TMDS. We found that the platelet count was significantly higher (p < 0.05),
      and the blast percentage of the bone marrow was significantly lower (p < 0.05) in
      the AML/TMDS group than in the AML/non-TMDS group. Sex ratio, age, WBC and RBC
      count did not significantly differ between the two groups. The immunological
      markers and the myeloperoxidase positivity of the blasts of AML/TMDS varied
      widely. The CR rate was 66.7% in the AML/TMDS group and 83.3% in the AML/non-TMDS
      group. Dysplastic changes were still detected in the bone marrow smears in 7 of 8
      AML/TMDS cases who achieved complete remission. The AML/TMDS group showed
      significantly shorter CR duration (median; 169 days) and survival (median; 511
      days, p < 0.05). However, in two cases which underwent allogeneic bone marrow
      transplantation (allo-BMT) during early relapse phase the disease-free survival
      has extended over 4 years and 2 years 8 months, respectively. Thus, we would like
      to propose that allo-BMT should be performed as early as possible to overcome
      poor outcome of AML/TMDS.

PMID- 7715092
TI  - Heterogeneity in lysosomal fusion with phagocytic vesicles and cell membrane in
      non-phagocytosing guinea-pig polymorphonuclear leukocyte.
AB  - The fusion of lysosomes and other granules with phagocytic vesicles (endo-fusion)
      and cell membrane (exocytosis) was simultaneously examined in non-phagocytosing
      guinea-pig polymorphonuclear leukocytes (PMNs). beta-Glucuronidase as a typical
      lysosomal enzyme, acid phosphatase as another lysosomal enzyme, and alkaline
      phosphatase as a specific granule enzyme were assayed. PMNs released these three
      enzymes in the presence of serum but the extents of exocytosis differed
      considerably: release of beta-glucuronidase, alkaline phosphatase and acid
      phosphatase was 6.9, 4.3 and 3.3%, respectively. Acid phosphatase was released
      even in the absence of serum, whereas the other two enzymes were not. These three
      enzymes showed also different responses in endofusion: the preformed phagocytic
      vesicles fused with the granules containing beta-glucuronidase and acid
      phosphatase, but scarcely fused with those containing alkaline phosphatase,
      although all these enzymes were recovered in increasing amounts in the
      phagolysosome fraction when the cells were allowed to phagocytose continuously.
      These results suggest that fusion of these three types of granules with
      phagocytic vesicles (endo-fusion) and plasma membrane (exocytosis) is
      heterogeneous and regulated by different mechanisms in guinea-pig PMNs.

PMID- 7715093
TI  - Class II-restricted presentation of an immunoglobulin heavy-chain-gene product by
      a gene-transfected B-cell line.
AB  - The presentation of an antigen endogenously processed by B lymphocytes was
      investigated. The expression plasmid vectors, harboring genomic rearranged V
      genes from two monoclonal B cells and genomic mu-constant region gene, were
      constructed. Two B-cell lines, the MOPC104E myeloma mu-heavy chain expressing AMB
      line and the control hybridoma mu-heavy chain expressing AHB line, were
      established by gene transfection into A20.2J B lymphoma cell line. The cloned
      transfectant cell lines expressed surface and cytoplasmic IgM.
      Radioimmunoprecipitation analysis of surface IgM revealed that both cell lines
      used transfected mu-heavy chain and host-derived kappa-light chain. The T-cell
      line, MRT-2, specific for the MOPC104E protein, proliferated on AME B cell lines
      but not on control AHB-cell lines. MRT-2 proliferation was inhibited by anti-I
      Ed,k,p,r but not by anti-I-Ad monoclonal antibody. Although the AME-transfectant
      lines secrete IgM into the culture medium, double chamber-type culture
      experiments revealed that MRT-2 proliferation is not mediated by the uptake of
      secreted IgM. The results suggest that B cells process and present their own
      immunoglobulin heavy-chain V-region peptides to T cells in the context of MHC
      class-II molecules.

PMID- 7715094
TI  - Trans-suppression of gene expression by hepatitis C viral core protein.
AB  - We have demonstrated that the truncated hepatitis C (HCV) core protein with its C
      terminal hydrophobic domains deleted is translocated to the nucleus of
      transfected cells (22). In this study, intact and truncated core proteins of HCV
      were transiently expressed in a human hepatoblastoma cell line, HepG2, and their
      effects on the expression of the chloramphenycol acethyl transferase (CAT) gene
      driven by viral and cellular promoters were examined. The intact core protein of
      22 kDa which is localized in the cytoplasm of the transfected cells suppressed
      the expression in all of the promoters tested. They were promoters of the SV40
      early region, the c-fos oncogene, the retinoblastoma susceptibility gene, the
      beta-interferon gene and the beta-actin gene. In contrast, the truncated HCV core
      protein located in the nucleus did not show such a suppressive activity. The HCV
      core protein appears to function not only as a viral structural protein but as a
      regulator of gene expression and it might act as a suppressive factor for the
      cellular gene expression.

PMID- 7715096
TI  - [24th Regional Meeting of East and West of Japan, Japanese Society of Nephrology.
      June 5-6, 1994, Abstracts].

PMID- 7715095
TI  - Epidemics of aseptic meningitis due to echovirus 30 in Japan. A report of the
      National Epidemiological Surveillance of Infectious Agents in Japan.
AB  - Two rages of epidemic of aseptic meningitis (AM) due to echovirus 30 (E30) in
      Japan were analyzed with respect to two sources of information, AM incidence and
      E30 isolation, both gathered through the National Epidemiological Surveillance of
      Infectious Diseases. The first E30 epidemic spread throughout Japan in 1983 and
      ceased within the year. The second epidemic, starting in 1989, continued for the
      three successive years, and in the last year, 1991, the total E30 reports
      numbered 4,061, the largest number of a single virus type ever reported. Although
      the epidemic showed temporal and geographical shift and lasted for one or two
      years in some areas, most laboratories reported the largest number of E30
      isolation in 1991. Among E30-yielding cases with clinical information during 1982
      1992, the associating frequency with AM was as high as 82.5%. Other central
      nervous system involvements such as encephalitis, myelitis, encephalomyelitis
      and/or paralysis were reported in 36 E30-yielding cases and their monthly and age
      distributions were different from those of AM cases. The proportion of such
      disease among E30-yielding cases (0.60%) was close to that of other enteroviruses
      (0.56%). During the epidemics, E30 was isolated more frequently from
      cerebrospinal fluid than was E4 or E9 which prevailed coincidentally. E30 was
      most frequently isolated from cases of 4-7 years of age, sharing the common
      characteristic pattern of age distribution with other enteroviral meningitis. E30
      yielding cases, however, involved a large number of older age groups than those
      of other enterovirus infections, and this tendency was the most pronounced in the
      first epidemic year, 1983. The contribution of these E30 epidemics on the yearly
      trend of clinically reported AM incidence and on the shift of its age
      distribution was also analyzed.

PMID- 7715097
TI  - [Quantitative analysis of myocardial tracer distribution in patients with
      ischemic heart disease: comparison of 201T1 and 123I-15-(p-iodophenyl)-3
      methylpentadecanoic acid (BMIPP)].
AB  - Quantitative assessment of myocardial tracer uptake in stress-delayed thallium
      and resting BMIPP imagings were performed in 24 patients with coronary artery
      disease. Each distribution was displayed on the bull's eye polar map and % uptake
      of each distribution was calculated as a mean value in 9 myocardial segments on
      the polar map. Redistribution index (% delayed uptake minus % stress uptake on
      thallium images) and discordance index (% delayed thallium uptake minus % BMIPP
      uptake) were also calculated. Each parameter was compared to the visual uptake
      score and wall motion score on contract left ventriculography. Excellent
      correlations were obtained between % uptake and the uptake score in each tracer.
      The % thallium and BMIPP uptake also correlated with regional wall motion score.
      Furthermore, a significant correlation was observed between redistribution and
      discordance indexes in the mildly hypoperfused segments. These data indicate that
      the quantitative analysis of thallium and BMIPP distributions seems to be
      valuable to understand relationship between perfusion and regional wall motion.
      The discordant BMIPP uptake may represent asynergic but viable segments. However,
      several important factors, such as attenuation factor should be also taken into
      consideration for such quantitative analysis.

PMID- 7715098
TI  - [Intrasubject comparison of regional cerebral blood flow between N-isopropyl-p
      [123I]iodoamphetamine SPECT and 99mTc-hexamethylpropyleneamine oxime SPECT in
      patients with ischemic cerebrovascular disease].
AB  - We compared regional cerebral blood flow (CBF) of CBF-SPECT brain imaging in two
      brain perfusion agents, N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and 99mTc
      hexamethylpropyleneamineoxime (99mTc-HMPAO), in the same patients with ischemic
      cerebrovascular disease. In eight healthy volunteers and 16 patients with chronic
      stage of cerebral infarction, single photon emission computed tomography (SPECT)
      data was normalized to the count density of the tracer in the whole brain, and
      then converted to the absolute units of CBF by multiplying average 133Xe-CBF in
      the whole-brain. One-way analysis of variance (ANOVA), grouped by the affected
      and contra lateral hemispheres of patients and right and left hemispheres of
      normal volunteers, was used to assess the changes in pattern of regional CBF
      (rCBF) among disease and control groups. Regional CBF was significantly reduced
      in patients compared with normal controls in all the brain regions on both
      tracers: F = 6.6-14 and p = 9.1 x 10(-4) - 1.6 x 10(-6) in IMP, and F = 5.8-14.8
      and p = 2 x 10(-3) - 8.2 x 10(-7) in HMPAO. F value was higher in IMP than that
      of HMPAO in five of nine brain regions of interests (the frontal, temporal and
      occipital cortices, thalamus and the striatum), whereas F value was higher in
      HMPAO than IMP in the other four regions (the central lobule, parietal cortex,
      hippocampus and the centrum semiovale).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715099
TI  - [Evaluation of renal function using 99mTc-MAG3 comparison with 131I-OIH by
      simultaneous dual energy peak acquisition method].
AB  - A newly developed 99mTc-labeled renal scintigraphic and renographic agent, 99mTc
      mercaptoacetyltriglycine (99mTc-MAG3) was studied clinically and compared with
      131I-OIH in 16 patients with various renal and urinary tract disorders. The
      abdominal aorta and the common iliac artery were clearly visualized in the
      vascular phase. The renogram patterns showed the same pattern in all cases. The
      parameters on the renogram such as Tmax, T2/3, T1/2 were compared. The highly
      significant correlations of Tmax, T2/3 and T1/2 were observed between 99mTc-MAG3
      and 131I-OIH with correlation coefficient of 0.982, 0.907, 0.990, respectively.
      In all cases, excretion of 99mTc-MAG3 was slower than that of 131I-OIH and the
      ratios of Tmax, T2/3 and T1/2 between 99mTc-MAG3 and 131I-OIH were 1.113 +/-
      0.121, 1.277 +/- 0.247, 1.179 +/- 0.075, respectively. It is concluded that 99mTc
      MAG3 is useful renal imaging agent as an alternative to 131I or 123I-OIH.

PMID- 7715100
TI  - [Evaluation of myocardial fatty acid metabolism in the area of fill-in after
      thallium reinjection in patients with prior myocardial infarction].
AB  - Myocardial fatty acid utilization in the area with thallium fill-in after
      reinjection was assessed using 123I-labeled 15-(p-iodophenyl)3R,S
      methylpentadecanoic acid (BMIPP). We studied 22 patients with prior myocardial
      infarction that revealed persistent defects on standard exercise-redistribution
      thallium imaging. In each patient, exercise-redistribution-reinjection thallium
      imaging was performed. Within two weeks of the thallium study, resting BMIPP
      imaging was performed 20 min after injection of BMIPP (148 MBq). Following
      qualitative analysis of the obtained thallium and BMIPP images, quantitative
      analysis was performed on the basis of relative regional uptake. Of 199
      myocardial segments that showed persistent defects on exercise-redistribution
      images, 73 segments showed apparent fill-in on the reinjection images (fill-in
      positive), and the remaining 126 segments did not (fill-in negative). When BMIPP
      images were compared with the corresponding thallium reinjection images, reduced
      BMIPP uptake compared with thallium were frequently observed in the area of fill
      in positive segments (65 of 73 segments, 89%). Quantitative analysis also showed
      decrease in BMIPP activity compared to thallium activity in the area of fill-in
      (49.7 +/- 16.1 vs. 65.8 +/- 16.0%, p < 0.001). In contrast, only 24 of the 126
      fill-in negative segments (19%) showed lower BMIPP uptake than thallium. These
      results suggest that impaired fatty acid utilization in the area of thallium new
      fill-in after reinjection already exists at resting condition.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7715101
TI  - [Evaluation of partial volume effect in quantitative measurement of regional
      cerebral blood flow in single photon emission computed tomography--effects of
      limited spatial resolution and first-pass extraction fraction].
AB  - Two numerical brain phantoms were generated in order to investigate errors which
      might be included in the quantitative measurement of regional CBF with use of
      single photon emission computed tomography (SPECT). The first phantom simulated
      the normal brain, and effects of the limited spatial resolution of the SPECT
      scanner were evaluated for 4 tracer kinetic models of the conventional
      microsphere model, the intra-carotid bolus injection technique of 133Xe, 133Xe
      Kanno-Lassen method, and the IMP-autoradiography (IMP-ARG) method. The second
      phantom simulated the diseased brain with middle-carotid artery (MCA) occlusion,
      and effects of the limited first-pass extraction fraction were investigated for
      the microsphere model with various permeability-surface area products. The
      limited spatial resolution caused systematic underestimation of the radioactivity
      concentration in the gray matter regions, and systematic overestimation in the
      low CBF regions. These errors in the original radioactivity distribution were
      found to cause further systematic errors in the calculated regional CBF images.
      It was also found that these errors were highly dependent on the tracer kinetic
      model employed, e.g., regional CBF values were overestimated in the clearance and
      the Kanno-Lassen methods compared with the conventional microsphere method,
      whereas values were underestimated in the IMP-ARG method. It was also shown in
      this study that the limited first-pass extraction fraction caused significant
      underestimation in the calculated rCBF values. In addition, regional contrast can
      be reduced when using a tracer with small PS product.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7715102
TI  - [Evaluation of partial volume effect in quantitative measurement of regional
      cerebral blood flow using positron emission tomography].
AB  - Effects of limited spatial resolution of the positron emission tomography (PET)
      scanner on the quantitative measurement of regional cerebral blood flow (rCBF)
      was investigated for various tracer kinetic models with use of 15O labeled water
      and PET. Using a numerical brain phantom consisting of a gray matter, white
      matter and cerebrospinal fluid components, dynamical tracer distribution images
      were calculated for the H215O bolus injection and for the C15O2 gas inhalation
      protocols. The tracer distribution images were convoluted with a 2 dimensional
      gaussian function with full-width at half maximum (FWHM) of 4, 7, 12 mm to
      simulate a limited spatial resolution of the PET scanner, and rCBF images were
      calculated according to some kinetic models. Smoothing the tracer distribution
      images caused a heterogeneous structure (tissue mixture) in a given volume
      element. rCBF values calculated by models with use of 15O-water and PET were
      found to provide rCBF values that were systematically underestimated compared
      with those obtained by the microsphere model for a mixed tissue region. Moreover,
      the magnitude of the underestimation was shown to be highly dependent on the
      tracer kinetic models employed, those errors for mixed tissue of gray and white
      matter were 20% on steady state, 9% on autoradiography and on weighted
      integration method, and 2% on non-linear least squares fitting, compared with
      microsphere model. More errors observed by steady state method and
      autoradiography method happened for tissue mixture consisting gray matter, white
      matter and cerebrospinal fluid components. It is important to take into account
      for difference of the partial volume effect for each models in calculated rCBF.

PMID- 7715103
TI  - [Usefulness of 123I-MIBG and 123I-BMIPP myocardial scintigraphy for detecting
      coronary artery disease and for evaluating left ventricular function].
AB  - We evaluated the diagnostic value of 123I-metaiodobenzylguanidine (MIBG) and 123I
      labeled beta-methyliodophenyl pentadecanoic acid (BMIPP) myocardial SPECTs for
      evaluating coronary artery disease and left ventricular function, in comparison
      with the diagnostic value of 201Tl (Tl) SPECT. For forty-nine patients with
      coronary artery disease, resting MIBG and BMIPP SPECTs were performed to detect
      coronary artery stenosis, compared with the diagnostic value of exercise Tl. Left
      ventricular ejection fraction and regional wall motion were compared with the
      total US (TUS) and regional US (RUS) of resting MIBG and BMIPP SPECTs, and in
      turn, compared with resting Tl SPECT. The sensitivity of resting BMIPP SPECT for
      detecting coronary artery stenosis was lower, and the specificity of resting MIBG
      SPECT was lower than the other two methods. The accuracy of resting MIBG SPECT
      for evaluating coronary lesions was nearly the same as the accuracy of exercise
      Tl, but higher than that of BMIPP SPECT. Left ventricular ejection fraction was
      well correlated with TUS of resting MIBG SPECT (r = 0.80), resting BMIPP SPECT (r
      = 0.77), and resting Tl SPECT (r = 0.68). Regional wall motion was most
      correlated with RUS of resting BMIPP SPECT, compared with that of resting Tl and
      MIBG SPECTs. These data suggest that resting MIBG SPECT is useful for detecting
      coronary artery disease and that resting BMIPP SPECT is valuable in evaluating
      regional left ventricular function.

PMID- 7715104
TI  - [A study of the simultaneous acquisition of dual energy SPECT with 99mTc and
      123I: evaluation of optimal window setting with myocardial phantom].
AB  - To examine crosstalks (CRs) between 99mTc-methoxyisobutyl isonitrile (MIBI) and
      beta-methyl-p-(123I)iodophenyl-pentadecanoic acid (BMIPP), myocardial phantom
      studies of simultaneous acquisition were performed with three window widths and
      four energies where the window located. CRS in 99mTc window were less than 10.5%
      regardless of the window settings. CRs in 123I window were ranging from 17.0% to
      8.6% depending on the window setting. There were significant correlations between
      the isotope concentration and counts of 99mTc and 123I, respectively (r = 0.98, p
      < 0.0001). We concluded that the optimal window setting of 99mTc-MIBI and 123I
      BMIPP (10% width, 140 keV center 99mTc window and 10% width, 164 keV center 123I
      window) yields good quality images in dual isotope SPECT.

PMID- 7715105
TI  - [Carbon-11 labeled diacylglycerol for signal transduction imaging by positron CT:
      evaluation of the quality and safety for clinical use].
AB  - To elucidate the synaptic transmission in the neural system, we have been
      developing fundamental studies for intracellular signaling. For clinical
      application of carbon-11 labeled diacylglycerol (1-[1-11C]butyryl-2-palmitoyl-rac
      glycerol: 11C-DAG) using positron emission computed tomography (PET), we
      evaluated the quality and the safety of 11C-DAG as the solution for injection. As
      a result, 11C-DAG was synthesized within 50 minutes, including the preparation
      step for injection. The half life time and energy spectrum of 11C-DAG were the
      same as the physical character of carbon-11, and other radioisotopes were not
      detected. In the quality control, 11C-DAG solution was negative in the
      examination of bacterial contamination and the pyrogen test in three successive
      synthesis procedures. In the acute toxicity test by administration of 11C-DAG and
      100 mumol/kg of non-radioactive DAG to the rat intravenously, the systemic
      condition of the rat was not changed and no abnormalities were found in any organ
      24 hours after administration. These findings indicated the safety of 11C-DAG
      solution. Clinical application of 11C-DAG using positron emission tomography may
      be useful to elucidate the dysfunction of intracellular signaling in disorders of
      higher cortical function such as Alzheimer disease.

PMID- 7715106
TI  - [Study on tumor accumulation property of 99mTc-HM-PAO and 99mTc-MIBI in rabbits
      bearing VX-2 cancer].
AB  - Each of blood flow imaging agents has a potential usefulness as an agent for
      tumor scintigraphy. The usefulness for tumor scintigraphy of two agents, i.e.
      cerebral blood flow scintigraphy agent 99mTc-HM-PAO and myocardial blood flow
      scintigraphy agent 99mTc-MIBI, was comparatively studied using rabbits bearing VX
      2 cancer. From then to twenty days after the implantation of VX-2 cancer into the
      femoral region of five rabbits, tumor to soft tissue accumulation ratio (T/S
      ratio) of each agent was calculated in early images (5 min after injection) and
      in late images (50 min after injection). Compared with 99mTc-MIBI, the T/S ratio
      of 99mTc-HM-PAO was higher and, moreover, the washout was delayed. These results
      suggest that there is a difference in tumor accumulation property between these
      two agents.

PMID- 7715107
TI  - [Comparison of inferior myocardial defect between planar and SPECT image of 123I
      metaiodobenzylguanidine cardiac scintigraphy].
AB  - Discordant findings of inferior MIBG defect between SPECT and planar images were
      sometimes observed in the clinical studies. In this study, we compared inferior
      myocardial findings between planar and SPECT image of 123I-metaiodobenzyl
      guanidine (MIBG) cardiac scintigraphy in 29 patients. All patients were estimated
      as normal in anterior accumulation of MIBG. The patients were divided into 3
      groups according to the visual finding of inferior defect in the planar and SPECT
      image; normal group (normal inferior accumulation of MIBG both in the planar and
      SPECT image, N = 10), discordance group (inferior MIBG defect was only observed
      in the SPECT image, but was not observed in the planar image, N = 7), inferior
      defect group (inferior MIBG defect was observed both in the planar and SPECT
      image, N = 12). Inferior/anterior count ratio of SPECT and planar image were 0.96
      +/- 0.11 vs. 0.97 +/- 0.05 in normal group, 0.59 +/- 0.21 vs. 0.99 +/- 0.13 in
      discordance group, 0.46 +/- 0.13 vs. 0.82 +/- 0.04 in inferior defect group.
      Liver/heart count ratio was significantly higher in the discordance group (2.07
      +/- 0.49) than that in the normal (1.14 +/- 0.15) and inferior defect group (1.45
      +/- 0.39). In phantom study, it has been reported that increased liver
      accumulation of MIBG causes artifactual inferior defect adjacent to the liver.
      These data indicate that increased liver/heart count ratio may cause artifactual
      inferior defect on MIBG SPECT image in the clinical studies. Planar image
      evaluation may be helpful to distinct the artifactual inferior defect on SPECT
      image.

PMID- 7715108
TI  - [Surgical treatment for ischemic mitral regurgitation in patients with poor left
      ventricle].
AB  - Results of CABG with and without mitral valve surgery were analyzed
      retrospectively in 81 patients with ischemic mitral regurgitation (MR) to
      determine the effects of severity of MR and surgical treatment on survival. Seven
      of 81 patients had severe MR (more than Sellers III degrees/IV). Of these 7
      patients, 5 patients underwent mitral valve replacement and 1 patient underwent
      mitral annuloplasty. Only one patient did not undergo valve surgery. This patient
      had slight improvement of the functional classification after CABG, but died of
      congestive heart failure 5 years after surgery. There were 3 hospital deaths and
      5 late deaths in 81 patients. Among the 29 patients with poor left ventricle (EF
      < or = 0.3), there were 3 hospital deaths and 2 late deaths. Postoperatively, 12
      patients had Sellers II degrees/IV or III degrees/IV MR. In 4 patients of these
      12, the severity of MR was aggravated in comparison with the preoperative
      severity. Three of these 4 patients had perioperative myocardial infarction
      (PMI). IABP was utilized preoperatively in patients with poor left ventricle to
      keep the stable hemodynamics and prevent PMI. In these patients, there were no
      PMI, no hospital death, or no aggravation of MR. In conclusion, patients with
      Sellers I degree/IV or II degrees/IV MR require CABG only, whereas those with
      Sellers III degrees/IV or IV degrees/IV MR need CABG combined with mitral valve
      surgery. Preoperative use of IABP is useful for preventing PMI and aggravation of
      MR in patients with poor left ventricle.

PMID- 7715109
TI  - [Development of operative procedures in general thoracic surgery].
AB  - The operative procedures in the general thoracic surgery developed or modified by
      us were reviewed and the developmental courses of each procedure were
      demonstrated. Lists of the procedures are as follows: 1) Extended thymectomy for
      myasthenia gravis. 2) Sternal elevation of Nagoya City University formula for
      pectus excavatum. 3) Anterior approach and hook approach for apical invading lung
      cancer. 4) Esophageal tracheoplasty for congenital tracheal stenosis and its
      application to various conditions.

PMID- 7715110
TI  - [One-stage repair of interrupted aortic arch with ventricular septal defect].
AB  - Three neonates with type A interrupted aortic arch were successfully repaired
      through a median sternotomy incision during profound hypothermia and circulatory
      arrest in the past one year. Two aortic cannulas, a small plastic one (Cardicorp)
      in the ascending aorta and a long one inserted through the pulmonary artery and
      patent ductus arteriosus into the descending aorta. Two Pacifico's venous
      cannulas were inserted into superior and inferior vena cavae respectively. No
      dissection and encircling were required around three major branches from the
      aortic arch and both right and left pulmonary arteries. During a cooling phase a
      large ventricular septal defect was closed followed by circulatory arrest. It was
      possible to resect a patent ductus arteriosus and mobilize the descending
      thoracic aorta for anastomosis to the side of the ascending aorta without removal
      of the aortic cannula in the aorta. New instruments and development of
      cardiopulmonary bypass could bring a successful one-stage repair of interrupted
      aortic arch with ventricular septal defect more safely and easily than before.

PMID- 7715111
TI  - [Initial ultrafiltration to the priming solution with preserved blood for
      cardiopulmonary bypass in infants].
AB  - In case of open heart surgery in infants, the initial priming solutions (IPS) of
      the cardiopulmonary bypasses (CPB) include considerable amount of preserved blood
      to assure us of the proper hematocrit during the CPB. Aiming at elimination of
      unfavorable effects of preserved blood on hearts and vessels, the
      ultrafiltrations (UF) to the IPS before the beginnings of CPB had been carried
      out in 42 pediatric cases. The IPS amounted to 915 +/- 25 (mean +/- SE) ml. in
      which 581 +/- 31 ml of preserved blood were included. The 1.5-fold amount
      infusions over the IPS, consisted of 5% glucose, normal saline and fresh frozen
      plasma, were added to the IPS, and just the same amount fluid were removed out by
      the UF. The concentrations of potassium, NH3, lactic acid and pyruvic acid in the
      IPS decreased significantly after UF (p = 0.001). The potassium concentrations
      were compared among the blood of patients (PB), the IPS before UF (IPS1), the IPS
      after UF (IPS2), and the mixed blood drawn 5-10 minutes after the beginnings of
      CPB (MB) in the cases under the age of 1 year (group-I, n = 26, 4.7 +/- 0.3 kg)
      and in the elders (group-E, n = 16, 15 +/- 2 kg). The results showed all
      significant differences but "IPS2 and MB" in group-I, and but "PB and MB" in
      group-E (ANOVA p = 0.001, p < 0.01 by Newman-Keuls). The 98% of cases kept their
      innate heart beatings until the aortic clamps at 22 +/- 1 degrees C (sending
      blood temp.).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715112
TI  - [Clinical result of left ventricular free wall rupture resulting from acute
      myocardial infarction].
AB  - We have treated 10 patients of left ventricular free wall rupture (LVFWR)
      resulting from acute myocardial infarction (AMI) in our intensive care unit (ICU)
      from Oct. 1984 to Dec. 1993. Nine of 10 patients underwent surgical repair,
      however, one patient was treated with pericardocentetesis in ICU and fibrin-glue
      was infused into the pericardial space (fibrin-glue therapy:FG therapy). The
      survival rate of surgical repair was only 33% (3/9), especially that was only 17%
      (1/6) when cardiopulmonary bypass (CPB) was required. One patient (49-year-old,
      male) suffered from cardiogenic shock following AMI in the posterior wall was
      performed coronary angioplasty (PTCA) in emergency and IABP support was required.
      Fourth day after PTCA, a sudden hemodynamical collapse had occurred on this
      patient due to cardiac tamponade. This patient was treated with
      pericardiocentetesis in ICU and FG therapy was performed, because all surgical
      teams were occupied in their operations. After FG therapy hemodynamical stability
      was obtained, the patient was survived and discharged at 2 months after LVFWR. In
      conclusion, the surgical result of LVFWR is still not good, especially when CPB
      was utilized. FG therapy was successful in one patient, suggesting FG therapy can
      be an alternative therapy for LVFWR when surgical team is not available.

PMID- 7715113
TI  - [Antihypertensive therapy using nicardipine hydrochloride in the treatment of
      aortic aneurysm].
AB  - A rapid and significant vasodepressor effect was obtained during acute stage
      before and after surgery on aortic aneurysm with continuous antihypertensive
      therapy using nicardipine hydrochloride. Twenty patients were treated; 6 patients
      had an acute dissecting aneurysm of the aorta, 8 were postoperative cases
      following resection of the thoracic aortic aneurysm, and 6 were postoperative
      cases of the abdominal aortic aneurysm. Nicardipine hydrochloride is easy to
      administer, has few side effects, and was found to be effective as
      antihypertensive therapy before and after surgery. The use of nicardipine
      hydrochloride has therefore been adopted by this unit as part of the treatment
      protocol for these patients.

PMID- 7715115
TI  - [Coronary artery-to-pulmonary artery fistula with aneurysm: two cases report].
AB  - We performed the operation for coronary artery-to-pulmonary artery fistula with
      aneurysm in two patients. The coronary angiograms of one patient, who was a 63
      year-old female, revealed coronary artery-to-pulmonary artery fistula originated
      from the left coronary artery with 3 aneurysms of 2 cm in diameter, respectively.
      The angiogram of another patient, who was a 77-year-old female, revealed coronary
      artery-to-pulmonary artery fistula originated from both coronary arteries with
      the giant aneurysm of 7 cm in diameter. We decided to operate by the reason of
      possibility of rupture of the aneurysms, and performed resection of the fistulas
      and the aneurysms with the closure of the drainage openings into the pulmonary
      artery with the aid of cardiopulmonary bypass. It was recommended to resect the
      coronary aneurysm before growing big in the patient with the coronary artery-to
      pulmonary artery fistula.

PMID- 7715114
TI  - [Mitral obstruction due to infective endocarditis: a case report].
AB  - Acute valvular obstruction caused by vegetation is a rare complication infective
      endocarditis. To our knowledge, only 9 cases and an autopsy case by Roberts have
      been reported since 1967. A 46-year-old man admitted with a chief complaint of
      pyrexia for 2 months duration. Within 24 hours of admission, the patient noticed
      of increased shortness of breath. Physical examination and the chest X-ray
      confirmed the pulmonary edema. An echocardiogram revealed a huge echogenic mass
      that was adherent to the mitral leaflet and obstructed the orifice completely.
      Soon after the patient fell into cardiogenic shock, an emergency mitral valve
      replacement was undertaken. At operation, multiple verrucae arising from the
      entire mitral leaflet was seen to occlude the orifice. The vegetation was excised
      and replaced with a # 25 Omnicarbon prosthesis. Postoperatively, the patient
      developed multiple organ failure caused by cardiogenic and septic shock which
      responded well to intensive medical treatment consisting of hemodialysis and
      continuous arteriovenous hemofiltration. Angiographically, a mycotic aneurysm in
      the left radial artery was found on the 18th postoperative day. After extirpation
      of the infective focuses, the postoperative course had stabilized. Mitral
      obstruction due to infective endocarditis is a fatal disease. Prompt diagnosis
      with echocardiogram and an emergency surgery should be undertaken to save the
      patient.

PMID- 7715116
TI  - [Clinical analysis of the surgical therapy of DeBakey type I acute aortic
      dissection].
AB  - We investigated relation of operative mortality with factors such as during from
      onset to operation, cardiac tamponade, age (more than 70 years old), aortic
      regurgitation, and shock. Fourteen patients underwent emergent surgery for
      DeBakey type I acute aortic dissection. These patients were the basis for this
      reports. Operative mortality was 43% (6/14). Although not statistically
      significant, there was a trend toward preoperative cardiac tamponade, namely the
      patients with preoperative tamponade had a poor prognosis. Causes of death were
      as follows, two patients related to the residual false lumen, two patients to
      surgical procedure, one patients to ischemic heart and one to mis-swallowing
      after operation. Among two patients who related to the residual false lumen, one
      died of rupture of the descending aorta that the clamping was performed during
      operation and the other occlusion of superior mesenteric artery 43 days after
      operation. Causes of deaths in patients in relation with surgical procedure were
      brain death and postoperative bleeding in 1 each. We concluded that the residual
      false lumen is a risk factor in the peri-operative stage.

PMID- 7715117
TI  - [Limited skin incision and partial median sternotomy for the repair of atrial
      septal defects in children].
AB  - Eight patients underwent the repair of atrial septal defect using the limited
      skin incision and partial median sternotomy. The average length of skin incision
      was 55% of the longitudinal size of the sternum. Our approach did not prolong the
      operation time and decreased the bloodloss. Moreover, postoperative events, such
      as hematoma, sternal instability, and wound infection, were not observed, and the
      cosmetic result was excellent. We think this method is safe and effective
      especially for children with atrial septal defect.

PMID- 7715118
TI  - [Thoracoscopic treatment of a giant bulla: a case report].
AB  - A 38-year-old man was admitted to our hospital because of left giant bulla and
      pneumothorax. His chest X-rays and CT scan showed giant bulla of the left upper
      lobe and left pneumothorax. We performed bullectomy using the ENDOPATH ENDO
      LINEAR CUTTER 60 mm and 35 mm disporsable surgical stapler under thoracoscopic
      guidance. Clipping with end-clips and fibrin glue were effective for miner air
      leakage. There were no complications such as prolonged air leakage or incomplete
      lung re-expansion. His post operative couse was uneventful and he was discharged
      from the hospital on the 11th post operative day. When performed along with mini
      thoracotomy, thoracoscopic operation is useful in treating patients with giant
      bulla.

PMID- 7715119
TI  - [Cavernostomy and muscle plombage with the pedicled latissimus dorsi and serratus
      anterior flap for recurrent large bullae with infection: a case report].
AB  - A 70-year-old male, who suffered from infection by MRSA and Aspergillus of the
      recurrent large bullae, was operated on cavernostomy for space sterilization.
      About three months later he underwent muscle plombage with the pedicled
      latissimus dorsi and serratus anterior flap. These muscles are ideal to place in
      open wound in the thorax because of the following reasons: These have the ability
      to eliminate local infection, a sufficient length and volume to obliterate an
      open cavity. And transposition of these muscles cause minimal functional upper
      extremity disability. Therefore, we considered that this technic was useful for
      the case of an infectious intrathoracic cavity with many bronchial fistulas.

PMID- 7715120
TI  - [Castleman's lymphoma presenting marked bronchial obstruction and compression of
      the great vessels: a case report].
AB  - A 24-year-old Caucasian male from Chile developed mediastinal Castleman's
      lymphoma, hyaline-vascular type, occupying from upper pre-tracheal to sub-carinal
      region, severely compressing the trachea, left main bronchus, pulmonary artery,
      and pericardium. Bronchofiberscopy demonstrated complete obstruction of the left
      main bronchus and the severe telangiectasis of the mucosa. The patient complained
      of the stridor and shortness of breath. The left thoracotomy had been performed
      in Chile, but unsucceeded in extirpation because of the adherence and the
      hypervascularity of the tumor. After 24 Gy irradiation, we performed the right
      thoracotomy and succeeded in extirpation of the tumor. It was the key for success
      that we could approach from right side under left sided unilateral ventilation.
      Castleman's lymphoma is not a rare disease, but the manifestation due to the
      bronchial obstruction is uncommon. So we present this case and review the
      literatures.

PMID- 7715122
TI  - [A case of CABG in a patient complicated with von Willebrand's disease secondary
      to polycythemia vera].
AB  - We report a case of 47-year-old patient with von Willebrand's disease (VWD)
      caused by polycythemia vera (PV) who underwent CABG surgery. The patient has been
      suffering of PV for 10 years and was admitted because of post infarction angina.
      On admission, she was found to have a decreased von Willebrand factor which was
      suggested by prolonged APTT. CABG was safely performed without undue bleeding
      with the use of Factor VIII concentrates. The appropriate control of polycythemic
      state before surgery and perioperative use of Factor VIII concentrates was
      considered to be important for successful open heart surgery associated with such
      complication.

PMID- 7715121
TI  - [Intraoperative hypoperfusion after coronary artery bypass grafting in a child
      with Kawasaki's disease: report of a case].
AB  - An 11-year-old boy with Kawasaki's disease who developed congestive heart failure
      due to acute myocardial infarction underwent coronary artery bypass grafting
      using the bilateral internal thoracic arteries. The surgical procedures were
      performed to the left anterior descending artery with the right internal thoracic
      artery and to the diagonal branch with the left internal thoracic artery with the
      aid of extracorporeal circulation and cardiac arrest with blood cardioplegia.
      About 30 minutes after the discontinuation of extracorporeal circulation,
      catastrophic ventricular fibrillation with acute left heart failure occurred
      because of coronary hypoperfusion. The cardiopulmonary bypass was reestablished
      after 20 minutes of resuscitation under cardiac massage. Additional saphenous
      vein graft bypass to the left anterior descending coronary artery that was
      already revascularized by the right internal thoracic artery was performed.
      Weaning from the cardiopulmonary bypass was then possible, and the patient were
      successfully treated using the delayed sternal closure technique. Use of the
      bilateral internal thoracic arteries appears to be beneficial in children with
      Kawasaki's disease to produce grafts in the growing heart, but the possibility of
      early catastrophic flow deterioration must be recognized because smaller arerial
      size provides inadequate nutritional support for the myocardium. The additional
      use of saphenous vein grafting might be beneficial in the case of severe coronary
      ischemia with small-sized internal thoracic arteries.

PMID- 7715124
TI  - [Treatment and etiology of spontaneous hemopneumothorax].
AB  - The incidence of spontaneous hemopneumothorax is reported to be 1-12% of all
      cases of spontaneous pneumothorax. We treated 152 cases of spontaneous
      pneumothorax in the past 8 years and hemopneumothorax occurred in 4 cases which
      is 2.6% of all cases of spontaneous pneumothorax. All the patients were male and
      the age ranged from 17 to 30. The total amount of blood loss ranged from 1,200
      3,200 mliters and surgical treatment was carried out within 2 days after
      admission. The bleeding point was visceral pleura of raptured bulla in 2 cases,
      parietal pleura of the torn adhesion in 1 case, and both visceral and parietal
      pleura in 1 case. Postoperative course was satisfactory and discharged within 2
      weeks after admission in all cases. The authors concluded that early thoracotomy
      is recommended for spontaneous hemopneumothorax.

PMID- 7715123
TI  - [Pseudoaneurysm of saphenous vein graft after CABG].
AB  - A 69-year-old man was admitted because of angina pectoris and thoracic descending
      aorta aneurysm. Staged operations were planned. First, he underwent CABG
      (coronary artery bypass grafting) with SVGs (saphenous vein grafts) to #4 PD, #7
      and #12. Aprotinin was administrated to reduce blood loss. The routine
      postoperative graft angiography and enhanced CT showed a pseudoaneurysm in the
      SVG to #4 PD. We planned an elective operation of pseudoaneurysm repair and graft
      replacement of thoracic descending aorta. Also in this second operation,
      continuous infusion of aprotinin was started after the induction of anesthesia.
      About 30 minutes later, he suddenly fell in shock and cardiac arrest. Partial
      cardiopulmonary bypass was established and median sternotomy was performed. In
      the mediastinum, no bleeding was found. We found out a bleeding point of the SVG
      to #4 PD and a hemostatic clip on the right ventricule, and closed the bleeding
      point with suture. The cause of the pseudoaneurysm seemed to be defluxion of the
      hemostatic clip for a side brunch of the SVG. The cause of the preoperative shock
      may be an anaphylaxis to readministrated aprotinin.

PMID- 7715125
TI  - [Long-term survival of a patient with lung cancer with skip metastasis to
      supraclavicular lymph nodes].
AB  - A case of lung cancer with skip metastasis to supraclavicular lymph nodes is
      described. The patient had undergone radical resection for gastric cancer about
      nine years ago. For about one year, chemotherapy had been done by Tegafur (600
      mg/day) after operation. Radical resection for lung cancer (p/d squamous cell
      carcinoma) was performed about seven years ago. Pathologically, mediastinal lymph
      node metastasis could not be detected. The needle aspiration biopsy of
      supraclavicular lymph node revealed metastasis. Then, radical neck lymph nodes
      dissection involving supraclavicular lymph nodes and radiation therapy were
      added. There has been no sign of recurrence so far.

PMID- 7715126
TI  - [Indication and choice of amputation level of the lower extremity in obliterative
      vascular diseases].
AB  - The work substantiates the indications for amputation of the lower limb in
      patients with obliterating diseases of the vessels. The main among them are
      progressive gangrene and decompensated ischemia of the limb in impossible
      performance of a restorative operation. It is pointed out that the level of the
      amputation should be chosen according to the condition of collateral circulation.
      Ultrasonic examination based on Doppler effect, allowing measurement of regional
      systolic pressure, is of principal significance in its evaluation. Analysis of
      the results of amputations in 111 patients with consideration for the value of
      regional systolic pressure showed that in 61 (51%) patients the amputation was
      performed through the leg or foot with immediate favorable results.

PMID- 7715127
TI  - [Immediate results of surgical treatment of pancreatoduodenal cancer].
AB  - The significance of two-stage treatment of obstructive jaundice caused by tumors
      of the terminal part of the biliary tract is shown on rich clinical material. The
      performance, in the first stage, of I.D. Prudkov's laparoscopic cholecystostomy
      which causes little trauma improved the accuracy of topical diagnosis to 95%. Its
      simple techniques and reliability made it accessible to a wide circle of
      surgeons. Preliminary decompression of the biliary tract increased operability to
      14.9% and reduced postoperative mortality to 8.9%. In cases in which a radical
      operation was not possible, the risk of a palliative intervention diminished and
      postoperative mortality reduced to 3.1%.

PMID- 7715128
TI  - [Role of polypeptides of pancreatic juice in the healing of intestinal
      anastomosis].
AB  - The possibility of using the polypeptide fraction of the pancreatic juice to
      accelerate healing of an intestinal anastomosis was studied in experiments. It
      was shown that the pancreatic polypeptides possess the properties of potential
      growth factors: after a single injection of these substances into the zone of the
      anastomosis during the operation, the synthesis of DNA and proteins in the
      tissues of the anastomosed intestinal segments essentially increases, which is
      evidence of stimulation of cell proliferation. Intensification of the
      proliferative processes in the tissues of the anastomosis improves the
      qualitative characteristics of the muscular suture-mechanical strength and
      biological air-tightness. The use of pancreatic polypeptides for acceleration of
      healing of an anastomosis formed in peritonitis showed this nontraditional method
      of protection of the intestinal suture to be very effective.

PMID- 7715129
TI  - [Carbohydrate metabolism in patients after pancreatoduodenal resection].
AB  - The authors studied carbohydrate metabolism 4 weeks to 12 months after
      pancreatoduodenal resection (PDR) in 21 patients whose ages ranged from 40 to 55
      years. Seven of them had been operated on for carcinoma of the major duodenal
      papillas and the other patients for carcinoma of the major duodenal papillas and
      the other patients for carcinoma of tree pancreas. The control group was formed
      of 10 healthy volunteers of the same age as the patients of the two groups under
      study; 10 patients who were subjected to PDR with pancreatojejunostomy and 11
      patients in whom resection of the pancreatic stump was completed by intraductal
      occlusion of the formed stump. None of them had disorders of carbohydrate
      metabolism before the operation. The patients were examined by the oral test for
      glucose tolerance (OTGT, 75 g of glucose) with glycemia determination and by
      intravenous glucose tolerance test (i.v. GTT) with determination of glycemia and
      C-peptide. It was found that the glycemia curves obtained during OTGT did not
      have a diabetic character according to the WHO criteria. In performing TTG, the
      coefficient K was diabetic in both groups. Study of the C-peptide level during
      the i.v. GTT showed that in the group with occluded ducts the level of the C
      peptide and the nature of its secretion differed obviously from those in the
      other groups under study, which testified to disturbances in the homeostai
      mechanisms.

PMID- 7715130
TI  - [Treatment of diffuse peritonitis].
AB  - From study of the values of central and peripheral hemodynamics in 369 patients
      with peritonitis of the diffuse form, it may be concluded that they reflect
      objectively the degree of intoxication. A hypodynamic reaction of the blood
      vascular system is a poor prognostic sign indicative of progressing peritonitis.
      Much significance is attached to morphological and microbiological study of the
      biopsy material of the parietal peritoneum, which allows judgement of the stage
      of peritonitis. Along with the traditional infusion and antibacterial therapy in
      peritonitis, UVI of autoblood and intravenous laser irradiation of the blood in
      stages IIA and IIB are applied. This should be followed by hemosorption which
      contributes to the active excretion of toxins from the organism. The authors
      recommend the method of programmed relaparotomy in stage IIB when there is a
      large amount of exudate with a collibacillary odour and a tendency to the
      formation of unterintestinal abscesses. Intraaortal infusion of medicinal agents
      is recommended in this clinical group marked by a tendency towards hypotension.
      In the group of 369 patients who underwent operation 112 (29.5%) died.

PMID- 7715132
TI  - [Premorbid conditions in traumatology (lecture)].

PMID- 7715131
TI  - [Outpatient surgical treatment of hemorrhoids].
AB  - The article analyses the treatment of hemorrhoids in our country and abroad,
      where outpatient treatment with latex rings is applied most frequently. The
      authors conducted 238 hemorrhoidectomies under conditions of outpatient clinics.
      They developed an operative method consisting in preventive compression of the
      base of the hemorrhoids with designs of alloy with "memory" of the shape. This
      method was used in 118 hemorrhoidectomies. No life-threatening complications
      occurred. Late-term recurrences were recorded in 1.6% of cases. It is claimed
      that hemorrhoidectomy can be performed in outpatient clinics if certain rules are
      observed. The is convenient for the patients and economically profitable for the
      State.

PMID- 7715133
TI  - [Reconstructive surgeries of lung cancer].
AB  - The proportion of reconstructive operations on the bronchi and tracheal
      bifurcation at the current level of the development of surgery for lung carcinoma
      is sufficiently high. Among 2,075 lung resections performed at our clinic
      reconstructive operations were carried out in 31.6% of cases. The success of
      reconstructive surgery in lung carcinoma is determined to a great measure by the
      correct choice of the indications for this type of surgical treatment,
      preoperative management, the level of surgical techniques and anesthesiological
      service, and postoperative management of the patients. Five-year survival
      depending on the stage and method of treatment after lob-, bilobectomy with
      resection and plastics of the bronchi and tracheal bifurcation was 28.3-67.4%,
      and after pneumonectomy with resection of the bifurcation of the trachea it
      ranger from 16.2 to 43.3%.

PMID- 7715134
TI  - [Computed tomography in the diagnosis of suppurative sacroiliitis in chronic
      pelvic osteomyelitis].
AB  - The object of the investigation was to study the possibilities of CT diagnosis of
      purulent sacroiliitis and evaluate the effect of its results on the choice of the
      volume of the surgical intervention and the operative tactics. The pelvis was
      examined in 15 patients with chronic hematogenic osteomyelitis of the pelvic
      bones; clinical signs of involvement of the sacroiliac articulation were
      encountered in 11 of them. There were 5 men and 6 women whose ages ranged from 18
      to 62 years. The results of examination of the sacroiliac articulation were
      appraised in its upper, middle, and lower levels. The computed-tomographic signs
      of purulent sacroiliitis are shown. It was established that computed tomography
      is an effective modern method of spot-film examination of the sacroiliac
      articulations for which the patient does not have to be specially prepared. It
      yields objective information on the condition of the pelvic bones, including the
      sacroiliac articulation. The method makes it possible to determine the
      indications for the operation, choose the best operative approach in each
      specific case, and to predict beforehand the volume of the operative
      intervention.

PMID- 7715135
TI  - [Cifran -- clinical effectiveness in the prevention and treatment of infection].

PMID- 7715136
TI  - [Postoperative suppurative complications and immune status in the surgical
      treatment of rectal neoplasms].
AB  - The authors studied the course of the disease in the postoperative period in 308
      patients with carcinoma of the rectum. The literature data and personal
      experience made it possible to reveal the high frequency of purulent
      complications among this category of patients. In view of this, the values of
      humoral and cellular metabolism were studied in some patients with uncomplicated
      forms of rectal carcinoma. Special attention was given for the first time to the
      peculiarities of local defence reactions of the peritoneum.

PMID- 7715137
TI  - [B2 microglobulin in the diagnosis and prognosis of postoperative infectious
      complications in the pulmonary surgery].
AB  - The radioimmunoassay was used to study blood serum B2-M levels in 56 patients
      with pulmonary diseases (lung carcinoma in 20, chronic suppurative lung disease
      in 20, and benign lung disease in 16 patients) before the operation and in the
      early postoperative period. The control group was formed of 21 practically
      healthy individuals. A direct correlation between the character of the course of
      the postoperative period in patients with benign and chronic pulmonary diseases
      and the dynamics of changes of immunoreactivity (IR) was found. A favorable
      course of the postoperative period was marked by an increase of IR, in
      postoperative infectious complications IR did not change. Dynamics of IR was not
      revealed in patients with lung carcinoma, irrespective of the course of the
      postoperative period.

PMID- 7715138
TI  - ["Jet scalpel" in the liver resection].
AB  - The use of the "jet scalpel" in liver resection allows the vascular-ductal
      structures to be adequately separated. This, in turn, prevents the risk of
      leaving hepatic areas devoid of blood supply or bile drainage, contributes to
      essential decrease of intraoperative blood loss, and decrease of the number of
      postoperative complications: bile seeping, biliary peritonitis, hepatic
      insufficiency, etc. The obtained results provide evidence that the use of the
      "jet scalpel" in surgical hepatology is advisable.

PMID- 7715140
TI  - [Lasers in the emergency surgery of abdominal cavity].

PMID- 7715139
TI  - [Pathogenesis of gastrointestinal functional disorders in peritonitis].

PMID- 7715141
TI  - [Local hemostatic agents from natural biopolymers. Report 2].

PMID- 7715142
TI  - [Arterial pulmonary thromboembolism as a cause of mortality in thoracic surgery].
AB  - Analysis of hospital mortality showed that thromboembolism of the pulmonary
      artery was a cause of lethal outcomes in thoracic surgery in 0.4% of hospitalized
      patients, in 0.7% of those who underwent operation, in 14.8% of all patients who
      died, and in 15.6% of those who died in the postoperative period. The principal
      causes of death in thromboembolism of the pulmonary artery were various
      diagnostic errors (79.5%), severity of the patient's initial condition (14.1%),
      and defective treatment (6.4%). Prevention of thromboembolism of the pulmonary
      artery is based on timely detection of its sources by wider use of ultrasonic and
      radionuclide methods, rarer application of invasive diagnostic methods, and the
      use of anticoagulant therapy after operations in the risk groups.

PMID- 7715143
TI  - [Results of electroneuromyographic study in patients after replantation of the
      lower extremities on the crus level].
AB  - We applied ENMG (electroneuromyography) in dynamics in the longterm postoperative
      period on 7 replanted segments of the lower limbs in 5 patients (in 2 patients
      both lower limbs were replanted). Seven nerve trunks were restored in 7 replanted
      segments. Analysis of the ENMG findings showed that restoration of the nerve
      trunks in replantation of amputated segments of the lower limbs through the crus
      restored conduction along the sensory and motor fibers in 56.3% of cases; in
      37.5% of cases conduction along the motor fibres was restored partly; conduction
      was completely absent along the sensory fibers in 45.7% and along the motor
      fibers in 6-7% of cases. ENMG makes it possible to evaluate the degree of
      restoration of the motor and sensory functions of the nerves after restoration of
      their continuity in replantation of large lower-limb segments at the level of the
      crus. The obtained quantitative data are sufficiently impressive arguments in
      favor of replantation of large segments of the lower limbs in serious traumatic
      amputation.

PMID- 7715144
TI  - [Doppler color ultrasonography in the evaluation of orbital and eyeball vessels].
AB  - 31 persons without any changes in visual system and 16 patients with vascular
      lesions were examined using Doppler colour ultrasonography. This method allowed
      to identify and evaluate the blood flow in central retinal artery, ophthalmic
      artery and in ciliary arteries. The authors described a typical picture of normal
      eyeball and orbita as well as the blood flow observed with Doppler pulsation
      wave. It was found that normal orbital veins were difficult to observe. The
      pathological changes of the blood flow in carotid artery occlusion, in arterial
      cavernous shunt and in retrobulbar neuritis were also described. The authors
      indicate a great diagnostic usefulness of the method.

PMID- 7715145
TI  - [Early and long-term results of retinal detachment surgery in ERG and static
      perimetry].
AB  - 39 patients selected at random from 130 operated on in the years 1987-1989 on
      account of retinal detachment in one eye were examined. The results of ERG and
      visual field examinations, performed at 10-12 days and 4-6 years and 4-6 years
      after surgery, were analysed in 30 patients with attached retina. The studies
      revealed an improvement of function of bipolar and glial cells and none in that
      of retinal photoreceptors. Significantly worse visual function was found in
      operated eyes in comparison with the fellow ones.

PMID- 7715148
TI  - [Intraoperative support of trabeculectomy with mitomycin].
AB  - The authors evaluated the efficacy of pharmacological support of trabeculectomy
      by intraoperative application of mitomycin. It was used in selected cases, those
      of high risk glaucoma as regards to poor surgical effect, in concentrations 0.2
      mg/ml and 0.5 mg/ml. There were 32 eyes with following types of secondary
      glaucoma: neovascular glaucoma in diabetes, glaucoma in aphakic and pseudophakic
      eyes and simple glaucoma in the eyes after uneffective trabeculectomy.
      Normalization of the intraocular pressure was achieved in 21 eyes (65.6%). The
      1.5-year follow-up revealed that with higher concentrations of mitomycin
      normalization of the pressure was more frequent lait there occurred more
      complications than with lower concentrations. Long-lasting hypotony is a
      difficult complication.

PMID- 7715146
TI  - [The fate of children after bilateral enucleation of the eyeball because of
      retinoblastoma].
AB  - The authors present the fate of children with particularly severe form of
      retinoblastoma, in whom despite of treatment both eye balls had to be enucleated.
      In Ophthalmological Clinic in Krakow there were 70 such cases in the last 30
      years, but information was obtained only about 52 children observed for at least
      5 years. From among those children 23 (45%) died because of metastases of the
      tumour. Among the surviving 29, 3 are deeply mentally retarded and remain in
      nursing homes. The further 22 children maintain average or normal level of mental
      development, despite the loss of both eyes, they attend schools for the blind and
      find their place in the society. The remaining four children are talented above
      average, surprisingly independent, and two among them are university graduate.
      Owing to the enucleation of the second eye with an advanced tumour the children
      survived and found their places in the society.

PMID- 7715149
TI  - [Treatment of accommodative myopia--preliminary report].
AB  - The authors present preliminary results of a special training of patients with
      accommodative myopia, using plus correction for long distance vision and
      prismatic correction for near vision, which decreased or compensated exotropia.
      60 patients have already been selected for this type of treatment but the results
      were evaluated only in 13, with 2-4 years' follow-up; 11 of them trained
      systematically, 2 were not exact in the recommended way of treatment.

PMID- 7715147
TI  - [Ocular changes in patients with tuberous sclerosis].
AB  - The authors discussed ocular changes observed in 100 children with tuberous
      sclerosis. Retinal tumors, typical of this disease, were found in 19 patients
      (19%). This incidence was higher in older children. Three types of tumors were
      observed: a) flat or slightly elevated, indistinct, salmon-grey colour, b)
      whitish-yellow, mulberry-like, located in disc area, c) mixed or intermediate.
      The authors observed 4 stages of tumors' development: changes in distribution of
      pigment in retina, arising of semitranslucent, salmon-grey tumors, mineralization
      of tumors-so called intermediate type, mulberry-like type. Progress from one
      stage to the next one is slow.

PMID- 7715150
TI  - [Non-surgical treatment of convergent strabismus with a localization method].
AB  - The results of non-operative treatment of 100 cases of convergent strabismus, 75
      with macular and 25 with eccentric fixation are presented. Two kinds of prismatic
      correction were applied: hyper-correction with alternative obturation and
      correction, exactly compensating the squint angle. The aim of the former one was
      to decrease the squint angle and help the eyes to be in prismatic orthotropy. The
      latter prisms enabled permanent symmetrical stimulation of the retina which lead
      to the development of normal binocular vision. The duration of the treatment was
      3-10 years. In all patients, parallel position of the eyes, normal binocular
      vision and improvement of visual acuity were achieved.

PMID- 7715151
TI  - [5-Fluorouracil in glaucoma surgery].

PMID- 7715152
TI  - [Pathomechanism of anatomical, clinical and functional lesions in primary open
      angle glaucoma and advances in diagnosis and monitoring].

PMID- 7715153
TI  - [Diagnostic difficulties of glaucoma in severely myopic eyes].

PMID- 7715155
TI  - [Rieger's syndrome in a 12 year old girl].
AB  - The authors presented a case of Rieger syndrome with typical sings and symptoms.
      Genetic conditionings and differentiation, especially with Axenfeld syndrome,
      were shown. The therapeutic problems with secondary glaucoma and the applied
      methods of successful pharmacological and surgical treatment were described.

PMID- 7715154
TI  - [Eyelashes in the eyeball after trauma].
AB  - The authors presented 3 cases of intraocular eyelashes, which entered into the
      eyeball during perforative injuries. Risk factors of such complications as well
      as clinical course and treatment are discussed. Reaction of the eye to this kind
      of foreign body was relatively weak. Difficulties in finding eyelashes during
      primary surgical procedure after trauma are emphasized.

PMID- 7715157
TI  - [Lensectomy in treatment of traumatic cataracts].
AB  - Results of pars plana lensectomy (36 cases) and ab externo lensectomy (14 cases)
      were presented. Intra- and postoperative complications, and the advantages of
      these procedures in traumatic cataracts were discussed. It was established that
      both procedures improved the visual acuity in the majority of patients although
      pars plana lensectomy had slightly lower rate of complications.

PMID- 7715156
TI  - [Influence of cryotherapy in the inhibition of collagenase activity in
      experimental corneal burns by hydrochloric acid. Doctoral thesis summary].
AB  - Investigations were carried-out on corneas of rabbit eyes burned with 1N HCl and
      then treated with low temperature. It was found that cryotherapy has advantageous
      influence on collagenase activity. In early period after burn cryotherapy could
      prevent collagenolysis and later inhibited collagenase activity.

PMID- 7715158
TI  - [Optic disc drusen--clinical picture and diagnostic problems].
AB  - The aim of the paper was to establish the methods which allow to diagnose optic
      disc drusen and to differentiate them from other diseases with similar clinical
      picture. 10 patients with diagnosis or suspicion of optic disc drusen were
      examined. The results suggest that usefulness of ultrasonography, fluorescein
      angiography and static perimetry.

PMID- 7715159
TI  - [Eye neoplasms during the developmental years based on personal observations].
AB  - The paper presents the results of the observations of 81 patients among 84 (44
      females and 40 males, aged 0 to 18 years) treated in the period 1990-1993 for
      neoplasms of the visual system. Surgery was performed in 73 of them (89%).
      Histopathological examinations of tumors define most of them as benign (96% and
      4%) as primary malignant.

PMID- 7715160
TI  - [Use of periocular and subfascial anesthesia in ophthalmic surgery].
AB  - The authors described the technique, usefulness and complications of 2 types of
      local anesthesia applied in patients who underwent ocular surgery. In 25 cases,
      peribulbar and in 136 sub-Tenon anesthesia were performed. Both methods were
      evaluated as efficacious. It was found that the simple and safer sub-Tenon
      anesthesia could replace retrobulbar blockade.

PMID- 7715161
TI  - [Complications of retro-ocular blockade and other methods of local anesthesia in
      ophthalmology].
AB  - The authors discussed local and general complications of retrobulbar blockade and
      methods of decreasing the risk of their occurrence. They also presented the
      usefulness and complications of other methods of local anesthesia such as
      peribulbar, subconjunctival, sub-Tenon and superficial.

PMID- 7715163
TI  - [Graefe's balance test in thyroid diseases].
AB  - Graefe's test for muscle balance was performed in 100 patients with nodular toxic
      goitre and Graves-Basedow, and in a control group of 100 healty people. The test
      was positive in 51% of the thyroid cases for short distance vision. In this group
      90% of disorders involved latent divergence, 10% latent convergence. In the
      control group the test was positive only in 3% of cases. Comparison of the
      Graefe's balance test with other methods of examination revealed that it is very
      sensitive; in Maddox test disturbances were found in 24% of patients, Moebius
      sign was observed in 8%, Dalrymple sign in 4% and exophthalmos in 9%. The authors
      concluded that Graefe's balance test is a simple examination which can be
      performed at the bedside and it should be remind.

PMID- 7715162
TI  - [Usefulness of occlusive foil in the treatment of low grade amblyopia in
      children].
AB  - Ryster Optik occlusive folia were applied in 75 children with lowgrade amblyopia.
      Improvement of the visual acuity and binocular vision were achieved in all cases.

PMID- 7715165
TI  - [Cavernous hemangioma of the retina and optic disc].

PMID- 7715164
TI  - [Carcinoma sebaceum of the upper eyelid--diagnostic problems].
AB  - The authors presented a case of a man, 44, with a rare malignant neoplasm of the
      upper eyelid, diagnosed after its second recurrence as carcinoma sebaceum. At
      first the lesion was considered to be a chalasion and histopathological diagnosis
      after the first recurrence was carcinoma spinocellulare. The authors tried to
      explain the differences between the 2 histopathological examinations and
      concluded that the clinical course of the case confirmed the necessity of this
      examination in every atypical recurrent chalasion.

PMID- 7715166
TI  - [Cardiovascular agents in anesthesia, intensive care and emergency medicine.
      Workshop proceedings].

PMID- 7715168
TI  - [Current status of cardiovascular monitoring].

PMID- 7715169
TI  - [Therapy of nonseptic cardiogenic circulatory failure].

PMID- 7715170
TI  - [Therapy of perioperative nonseptic, noncardiogenic circulatory failure].

PMID- 7715167
TI  - [Characterization of cardiovascular changes in intensive care and objectives of
      adequate cardiocirculatory therapy].

PMID- 7715171
TI  - [Therapy of septic cardiovascular failure].

PMID- 7715172
TI  - [Special aspects of cardiovascular therapy within the scope of emergency
      medicine].

PMID- 7715174
TI  - [Vasogenic hypotension--causes, effects, therapy].

PMID- 7715173
TI  - [Acute arterial hypertension--causes, effects and therapy].

PMID- 7715175
TI  - [The ischemic heart--causes, effects and therapy].

PMID- 7715176
TI  - [Chronic pulmonary hypertension--causes, effects, therapy].

PMID- 7715177
TI  - [Acute pulmonary hypertension (pulmonary embolism)--causes, effects and therapy].

PMID- 7715180
TI  - [Pre-, intra- and postoperative heart failure: diagnosis, treatment strategies
      and control of effectiveness].

PMID- 7715178
TI  - [Pathophysiology of myocardial ischemia].

PMID- 7715179
TI  - [Clinico-pharmacologic aspects of cardioactive drugs].

PMID- 7715181
TI  - [Pre- and intraoperative arrhythmias--evaluation and treatment strategies].

PMID- 7715182
TI  - [Care of patients with systemic hematologic diseases].

PMID- 7715183
TI  - [Experience of sorrow and faith in resurrection].

PMID- 7715184
TI  - [Weak places].

PMID- 7715185
TI  - [The tautly stretched bedsheet as a trigger for decubitus ulcers].

PMID- 7715186
TI  - [Behavior and action to take as well as legal responsibility of the nursing
      personnel in decubitus ulcers].

PMID- 7715187
TI  - [Comparative decubitus risk scales].

PMID- 7715189
TI  - [Prevention of decubitus ulcers in the operating room].

PMID- 7715188
TI  - [Example of a standardized decubitus ulcer therapy (stage I-III)].

PMID- 7715191
TI  - [Consequences of increasing occurrence of decubitus ulcers: effective
      prevention].

PMID- 7715192
TI  - Gas exchange in the insect tracheal system.
AB  - The role of the insect tracheal system in gas exchange during cyclic ventilation
      is investigated using mathematical models. Three models are presented, one to
      describe the important elements of gas exchange during each of the three phases
      of cyclic ventilation. The effects of normobaric hypoxia on gas exchange are then
      examined, first assuming the initial parameter values set for the tracheal system
      and, second, assuming conditions of tracheal hypertrophy produced by an increase
      in the cross-sectional area of the tubes in the tracheal system. An increase in
      tracheal tube cross-sectional area is an important adaptation to normobaric
      hypoxia, but only if the tracheae themselves are the primary sites of resistance
      to gas exchange. Under conditions where the spiracles are the sites of resistance
      to gas exchange, volume expansion of the tracheae, not an increased cross
      sectional area per se, is the important adaptation to normobaric hypoxia.

PMID- 7715190
TI  - [Standardized prevention of decubitus ulcers in a surgical intensive care unit
      and differential-therapeutic considerations on the use of special anti-decubitus
      beds].

PMID- 7715193
TI  - A theoretical study of cytosolic calcium waves in Xenopus oocytes.
AB  - Calcium waves have been observed in Xenopus oocytes through the use of confocal
      fluorescence microscopy. The waves assume many patterns including plane waves,
      target patterns and spirals. Modification of the membrane model (Jafri et al.,
      1992) to include diffusion terms in two dimensions reproduces planar and circular
      propagating waves. A one-dimensional model is used to study the properties of
      these waves. The model predicts that increasing the buffering capacity of the
      cytosol decreases the wave amplitude and speed. A decrease in the wave speed is
      also observed when the net calcium entry rate into the cytosol decreases. The
      model also predicts that as the diffusion constant is increased, the wave speed
      increases.

PMID- 7715194
TI  - An investigation into the role of phenotypic plasticity in evolution.
AB  - Phenotypic plasticity can modify evolutionary pathways and accelerate the course
      of evolution. This was brought out in a quantitative model by Hinton & Nowlan
      (1987, Complex Systems 1, 497-502). The present work confirms and extends their
      results. We consider a population of genetically haploid individuals of fixed
      size. Genotypes are represented by one-dimensional arrays (strings) of genes.
      Each gene can be in one of three allelic states, designated 1, 0 and X. 1 and 0
      stand for fixed states, that is for states with predetermined effects on the
      phenotype. X stands for a plastic state: the phenotypic effect of an X can be
      equivalent to that of a 1 or a 0, the actual choice being realized by a process
      of random coin-tossing. Our model, in contrast to that of Hinton and Nowlan,
      assumes a relatively smooth dependence of fitness on distance from a pre-assigned
      target genotype. From the fitness values, the number of individuals reaching
      reproductive maturity is determined. Reproduction involves random mating and a
      single recombinational event, with one of the two progeny genotypes becoming, in
      turn, a possible parental genotype for the next generation. We find that it is
      because of the special assumptions in the Hinton and Nowlan model that phenotypic
      plasticity invariably accelerates evolution. The relationship is not as
      straightforward with realistic fitness schemes. Instead, the general result is
      that plasticity, up to a certain optimal level, slows down the rate of
      evolutionary change but improves the level of adaptation finally reached.

PMID- 7715195
TI  - Evolutionary conservation of both the hydrophilic and hydrophobic nature of
      transmembrane residues.
AB  - An algorithm (HRG), developed to allow the pairwise comparisons of the aligned
      residues of several members of large gene families of polytopic integral membrane
      proteins is described. Using hydrophobicity scales, application of this algorithm
      allows the number and size of the membrane-spanning domains of bacteriorhodopsin,
      a polytopic protein whose structure has been partially determined, to be
      predicted with a high degree of accuracy (sensitivity 94%, specificity 82% for
      predicting the membrane embedded or extramembranous location of residues). As
      opposed to previously reported structure-prediction algorithms, delineation of
      putative transmembrane segments from connecting loops is also more clearly
      evident with the application of the HRG algorithm, even with proteins from widely
      divergent species. This indicates strong evolutionary pressure for the
      conservation of both the hydrophobic and hydrophilic character of residues in
      membrane-embedded regions of polytopic proteins, such as those of the G-protein
      coupled receptor superfamily. These and other structural and functional
      implications evident from the application of the HRG algorithm are considered.

PMID- 7715196
TI  - Predictive study of the conformation of the cytotoxic protein alpha-sarcin: a
      structural model to explain alpha-sarcin-membrane interaction.
AB  - Alpha-sarcin is a cytotoxic protein composed of a single polypeptide chain. This
      protein shows a significant degree of amino acid sequence similarity with a group
      of several phylogenetically related fungal ribonucleases. The leading member of
      such a group is ribonuclease T1. Three proteins of this group, ribonucleases T1,
      Ms and F1, are well known in terms of their crystal structures. These data have
      been used to propose a conformation for alpha-sarcin. The secondary structure of
      the cytotoxin would contain one alpha-helix segment as well as around six beta
      strands and 14 beta-turns. The folding of these structural motifs is proposed by
      comparison with the three-dimensional structure of the three proteins from the
      ribonuclease T1 subfamily. The four longest beta-strands of alpha-sarcin would
      define an antiparallel beta-sheet structure resulting in a highly hydrophobic
      domain. The predicted folding for alpha-sarcin is discussed in terms of the
      ability of this protein to electrostatically and hydrophobically interact with
      phospholipid vesicles. The proposed conformation would explain how a highly polar
      protein, such as alpha-sarcin, can produce membrane destabilization resulting in
      protein translocation across lipid bilayers.

PMID- 7715197
TI  - Cysteine-string proteins as templates for membrane fusion: models of synaptic
      vesicle exocytosis.
AB  - Cysteine-string proteins are relatively small, cysteine-rich components of
      synaptic vesicle membranes. Recent investigations demonstrated that at least 11
      of the 13 cysteine residues of the Torpedo cysteine-string protein are fatty
      acylated. This exceptional level of fatty acylation occurs along a short stretch
      (less than 25 residues) of amino acids which are flanked on either side by very
      polar amino and carboxy termini. This amphipathic structure may have unique
      capabilities to catalyze events at membrane interfaces. We propose two distinct
      pathways to explain how these capabilities might subserve membrane fusion and
      exocytosis.

PMID- 7715198
TI  - Identification and simulation of shifted periodicities common to protein coding
      genes of eukaryotes, prokaryotes and viruses.
AB  - The distribution of nucleotides in protein coding genes is studied with
      autocorrelation functions. The autocorrelation function YRY(N)iYRY, analysing the
      occurrence probability of the i-motif YRY(N)iYRY (two motifs YRY separated by any
      i bases N, R = purine = Adenine or Guanine, Y = pyrimidine = Cytosine or Thymine,
      N = R or Y) in the protein coding genes of eukaryotes, prokaryotes and viruses,
      reveals the classical periodicity 0 modulo 3 associated with the normal frame 0
      (maximal values of the function at i = 0, 3, 6, etc). The specification of
      YRY(N)iYRY on the alphabet [A, C, G, T] leads to 64 i-motifs: CAC(N)iCAC,
      CAC(N)iCAT, ..., TGF(N)iTGT. The 64 autocorrelation functions associated with
      these 64 i-motifs in protein coding genes have all the periodicity modulo 3, but,
      surprisingly, not always the expected periodicity 0 modulo 3. Two new types of
      periodicities are identified: a periodicity 1 modulo 3 associated with the
      shifted frame +1 (maximal values of the function at i = 1, 4, 7, etc) and a
      periodicity 2 modulo 3 associated with the shifted frame -1 (maximal values of
      the function at i = 2, 5, 8 etc). Furthermore, the classification of i-motifs
      according to the type of periodicity demonstrates a strong coherence relation
      between the 64 i-motifs, which is, in addition, common to the three gene
      populations, as the same i-motifs in the three gene populations have the same
      periodicities. The three periodicities 0, 1 and 2 modulo 3 can be simulated by an
      evolutionary model at two successive processes. The simulated genes are generated
      by a process of gene construction, with a stochastic automaton followed by a
      process of gene evolution with random insertions and deletions of trinucleotides
      simulating RNA editing. For almost all i-motifs, the autocorrelation functions in
      these simulated genes are strongly correlated with those in protein coding genes,
      for both the type and the probability level of periodicities. This paper
      describes the process of ribosomal frameshifting leading to the shifted
      periodicities, which may reveal overlapping genes or concatenated genes from
      different frames. It also presents the evolutionary aspects of the shifted
      periodicities. The shifted periodicities cannot be associated with the RNY model
      (Eigen & Schuster, 1978, Naturwissenschaften 65, 341-369) or the RRY model (Crick
      et al., 1976, Origins of Life 7, 389-397), but are compatible with the
      oligonucleotide mixing model (Arques & Michel, 1990, Bull. math. Biol. 52, 741
      772). Finally, a variant of the primitive translation model of Crick et al.
      (1976) is proposed to explain the shifted periodicities.

PMID- 7715200
TI  - Statistical analysis of drug interactions in anesthesia.
AB  - Anesthesiologists often use more than one drug in a patient to achieve a target
      response, such as a desired blood pressure. Isobolographic analysis is a standard
      mathematical method to test whether a drug-drug interaction exists and, if so,
      whether the interaction is synergistic or antagonistic. Several experimental
      protocols are suitable to collect data for interpretation by isobolographic
      analysis. Traditionally, each subject would receive a single dose of one or more
      drugs and the presence or absence of the target response in the subject at a
      specific time would be recorded. An alternative procedure is to infuse one or
      more drugs into each subject until the target response occurs. This procedure is
      clinically relevant to studies of anesthesia drugs, which are often titrated to
      achieve a target response. This latter method of testing for drug interaction
      requires fewer subjects than the traditional approach because more information is
      obtained from each subject. We present a statistical test for drug-drug
      interaction that uses the total doses of drugs given to each subject. This
      statistical test can be used as part of a complete analysis of drug-drug
      interaction. We consider (i) selection of appropriate sample sizes and doses;
      (ii) randomizing subjects to groups; (iii) effects of unequal group variances on
      the accuracy of the statistical test; (iv) appropriate methods to present the
      drug-drug interaction data graphically; and (v) tests to ensure that statistical
      assumptions are satisfied. Using the statistical methods described here, drug
      drug interaction can be quantified and evaluated for statistical significance.

PMID- 7715199
TI  - Understanding the biomechanics of tendon fibrocartilages.
AB  - A direct analogy with the function of large proteoglycans in articular cartilage
      has led to the assumption that the presence of such components in tendon
      fibrocartilages is a major factor enabling these structures to resist pressure.
      However, the association of collagen fibrils in bundles and their tensional state
      as verified through the existence of crimp under polarized light in tendon
      fibrocartilage raises doubts as to whether the large proteoglycans are kept under
      osmotic pressure, which is an essential condition for their physiological role in
      articular cartilage. This suggests that tendon fibrocartilage has distinct
      mechanisms to resist pressure. In tendon fibrocartilages, the compressive forces
      must be transferred to the inextensible collagen fibers which lie in many
      directions in different planes, before reaching the parallel fibers of the
      tension region. In this sense, the large proteoglycans are likely to have the
      function of providing a viscous and cohesive environment in which collagen fibers
      could get stretched to reinforce the tissue.

PMID- 7715201
TI  - Developmental mechanics determine long bone allometry.
AB  - Evolutionary and developmental factors responsible for the scaling relationships
      observed in animal skeletons are poorly understood. We have created a
      mathematical model for long bone cross-sectional development which incorporates
      both intrinsic growth and extrinsic, adaptive bone modeling in response to
      changes in bone mechanical strains during ontogeny. The model successfully
      simulates the developing morphology in individual animals and the bone geometric
      allometric relationships among adults across many species (range from mouse to
      elephant in size). Our results suggest that long bone scaling characteristics are
      not a result of intrinsic genetic factors but are the results of highly
      conserved, extrinsic biophysical processes whereby bone tissue strains modulate
      skeletal morphogenesis.

PMID- 7715202
TI  - Lateral geniculate lamination and the corticogeniculate projection: a potential
      role in binocular vision in the quadrants.
AB  - Students of vision have long speculated about the functions of the distinct
      lamination of the lateral geniculate nucleus and the massive return projection
      from visual cortex to this thalamic structure. This paper proposes that these
      features of the visual system reflect, in part at least, its solution to a
      geometric problem inherent in binocular vision. Points in the visual quadrants
      are imaged on geometrically non-corresponding retinal points. Two such retinal
      loci, optically conjugate with a given visual point at one fixation distance or
      angle, will correspond to no single visual point at other fixation distances or
      angles. This raises potential problems for visual cortical neurons sensitive to a
      narrow range of binocular disparities. If these neurons are to function optimally
      at a variety of fixation distances and angles, their disparity tuning must be
      variable. It is suggested here that such dynamic disparity tuning is effected by
      the corticogeniculate projection acting on the segregated ocular representations
      in the geniculate laminae.

PMID- 7715203
TI  - Fine tuning of intracellular protein concentrations, a collective protein
      function involved in aneuploid lethality, sex-determination and speciation?
AB  - The assertion that sex chromosome dosage compensation arose because aneuploidy
      for an entire chromosome is lethal, begs the question of why aneuploidy is
      lethal. It has been proposed that aneuploid lethality results from impairment of
      a collective protein function (Forsdyke, 1994, J. theor. Biol. 167, 7-12).
      Cytosolic proteins, by virtue of their concentrations, exert a pressure tending
      to drive members of individual protein species into self-aggregates. Other
      evolutionary time, each gene has fine-tuned the concentration of its product to a
      maximum consistent with avoiding self-aggregation in the crowded cytosol. Because
      of this aggregation pressure and the imprecision of their own fine-tuning, the
      proteins of members of other species, the corresponding genes of which may have
      been transported to a cell as viruses (or gametes), are specifically aggregated.
      The death of the cell and its enclosed virus results. Aneuploidy impairs this
      process, with lethal consequences for the organism. The hypothesis leads to
      explanations for a variety of phenomena. On the assumption that the concentration
      of autosomal products determines cell volume, the observed dependence of sex
      determination on the ratio of X chromosomes to autosomes is shown merely to be a
      dependence on the concentration of the products of one X chromosome. The
      inviability of the heterogametic sex among the offspring of an interspecies cross
      (Haldane's rule), follows from the species-specific fine-tuning of the
      concentrations of X chromosome-encoded products relative to the concentration of
      autosomally-encoded products. Species may initially have evolved as a barrier
      behind which fine-tuning could occur to protect cells against intracellular
      pathogens.

PMID- 7715204
TI  - Nearest-neighbor distribution of interacting biological entities.
AB  - In this paper, spatial patterns exhibited in many biological systems are studied,
      based on the principle of maximum entropy. A general mathematical expression of
      the nearest-neighbor distribution is derived for a class of interacting
      biological organisms--structures range from cells in a tissue to trees in a
      forest.

PMID- 7715205
TI  - Can periodic breathing have advantages for oxygenation?
AB  - A model of the chemoreceptor mediated control of breathing is analysed. Hypoxia
      is simulated as low equilibrium arterial oxygen both at altitude and at sea
      level. Conditions for stable and unstable equilibria are examined. Transition to
      instability leads to periodic breathing and the model predicts that this can
      cause arterial oxygen to oscillate asymmetrically about the equilibrium in some
      cases, causing the average to rise. Periodic forcing functions have been applied
      to cerebral blood flow with the same effect on arterial oxygen. Such asymmetric
      oscillations leading to enhanced oxygenation have been observed in pulse oxymeter
      recordings from elderly postoperative patients. This may be important in
      interpreting studies of unstable breathing patterns and their possible relation
      to morbidity or mortality in infants (e.g. SIDS) and in the elderly (e.g. sleep
      apnoea, postoperative hypoxia). Periodic breathing could act as a protective
      adaptation to counteract pre-existing hypoxia.

PMID- 7715207
TI  - Alteration in synonymous arginine codon preferences of Bacillus subtilis during
      sporulation.

PMID- 7715208
TI  - Simultaneously stapled lobectomy: a safe technique for video-assisted thoracic
      surgery.
AB  - Currently, techniques for video-assisted thoracic surgery are being borrowed from
      the open conventional thoracotomy. However, these same techniques have made video
      assisted lobectomy difficult, burdensome, and even dangerous. Simultaneously
      stapled lobectomy (simultaneous stapling of all hilar structures in their natural
      anatomic configuration) has been performed successfully in 16 patients. Every
      attempted simultaneously stapled lobectomy is included. The lesions included 14
      malignant tumors, one giant benign pulmonary cyst, and one large necrotizing
      granuloma. Three right upper lobes, one right middle lobe, six right lower lobes,
      four left upper lobes, and two left lower lobes were resected uneventfully. Nine
      adenocarcinomas, two large cell carcinomas, and three squamous cell carcinomas
      ranging in size from 2.5 to 5 cm were removed. Lung fissures, the hilum, and the
      mediastinum were explored for lymph nodes in each patient. Median operative time
      was 110 minutes. Average blood loss was less than 100 ml. Median hospitalization
      was 6 days, although eight patients were discharged between 3 and 5 days. Three
      patients had air leaks for an average of 14 days and one patient had mild
      subcutaneous emphysema for 5 days. There was no surgical mortality. Median follow
      up is 15 months (range 8 to 20 months). Simultaneously stapled lobectomy is not
      meant to replace conventional lobectomy by open thoracotomy. Indications are
      cardiac or renal problems, contralateral chest wall paralysis, neurogenic
      deficiencies, adamant refusal to undergo open lobectomy, psychologic aberrations,
      and pain from a previous thoracotomy. Contraindications include absent fissures,
      enlarged matted invasive nodes, fibrotic hilum, central or bulky lesions,
      calcific bronchi, chest wall invasion, and lesions crossing a fissure. Precedent
      for this technique will be discussed. When used with discretion in carefully
      selected patients, in whom an open lobectomy would be contraindicated,
      simultaneously stapled lobectomy might eventually prove to be another available
      option. Time and further experience will be necessary to determine its true
      merits.

PMID- 7715209
TI  - Prevalence of ectopic thymic tissue in myasthenia gravis and its clinical
      significance.
AB  - Forty patients with myasthenia gravis underwent maximal thymectomy. Complete
      histologic study findings were available for 38 patients. The prevalence of
      ectopic thymic tissue was 39.5% (15 of 38). On the basis of the presence or
      absence of ectopic thymic tissue, patients were divided into two groups: group I
      had ectopic thymic tissue and group II had no ectopic thymic tissue. Male/female
      ratio was almost equal (1.1:1) in group I, whereas in group II the ratio was
      1:2.8. The duration of the disease was less than 1 year in 80% of group I and
      47.8% of group II patients (p = 0.05). Furthermore, ectopic thymic tissue (group
      I) was associated with poor outcome of operation (p = 0.003). Only 2 (13.3%) of
      15 patients in group I had complete remission as compared with 11 (47.8%) of 23
      patients in group II. Thus it appears that the presence of ectopic thymic tissue
      not only modifies some of the clinical parameters of myasthenia gravis, but also
      could serve as a prognostic factor in predicting the outcome of operation.

PMID- 7715206
TI  - Conditions under which Na+ channels can boost conduction of small graded
      potentials.
AB  - It has recently become apparent that in the dendrites or short axons of some
      neurons, voltage-dependent sodium channels are used not to generate action
      potentials but to modulate graded potentials; graded potentials carry far more
      information than do action potentials. A model axon (or dendrite) is described in
      which sodium channels with kinetics described by equations of the Hodgkin-Huxley
      type boost conduction of small voltage signals. For a sodium channel density
      beyond a certain minimum there exists an optimal potential, depolarized with
      respect to the resting potential, at which there is no steady-state decrement
      along the axon. For an axon not longer than about 0.7 length constants, small,
      steady-state deviations from this optimal potential imposed at one end of the
      axon appear amplified in a graded and stable way at the other end. A small pulse
      of potential is propagated with amplification and more rapidly than in an axon
      with a passive membrane. Compared to passive propagation, there will be an
      improvement in signal-to-noise ratio at the synapse; the axon also acts as a
      selective frequency filter. The same axon is capable of conducting an action
      potential.

PMID- 7715210
TI  - A prospective study on the effect of the Belsey Mark IV 270-degree fundoplication
      on lower esophageal sphincter characteristics and esophageal body motility.
AB  - The effect of the Belsey Mark IV operation on lower esophageal sphincter
      characteristics and esophageal body motor function was prospectively studied in
      38 patients who underwent successful operation (relief of symptoms, healing of
      esophagitis; group I) and 8 who had surgical failure (group II). Mean follow-up
      was 3 years (0.5 to 8 years). Only in group I a rise in basal lower esophageal
      sphincter pressure (from 8.3 +/- 0.8 mm Hg to 14.5 +/- 0.5 mm Hg, p < 0.001),
      total sphincter length (from 2.7 +/- 0.1 cm to 3.4 +/- 0.1 cm, p < 0.001), and
      the intraabdominal sphincter segment (1.3 +/- 0.1 cm to 2.3 +/- 0.1 cm, p <
      0.001) with a reduction of the intrathoracic segment (from 1.5 +/- 0.1 cm to 1.1
      +/- 0.1 cm, p < 0.05) was recorded. Preoperative and postoperative lower
      esophageal sphincter pressure and length values showed a large overlap.
      Antireflux operation had no effect on peristaltic amplitude, velocity, and
      duration, irrespective of the outcome of operation. One of five patients with
      incomplete swallow-induced lower esophageal sphincter relaxation had moderate
      dysphagia. Successful operation by 270-degree fundoplication is accompanied by a
      significant increase in lower esophageal sphincter pressure and length and does
      not affect esophageal body motor function.

PMID- 7715211
TI  - Late results of systemic atrioventricular valve replacement in corrected
      transposition.
AB  - From December 1964 to October 1993, 40 patients (aged 5 months to 70 years, mean
      21.8 years, median 13.6 years) with corrected transposition and systemic
      atrioventricular valve insufficiency underwent replacement (n = 39) or repair (n
      = 1) of the systemic atrioventricular valve. Thirty-nine patients had situs
      solitus and 1 had situs inversus. Associated anomalies included Ebstein's
      malformation of the systemic atrioventricular valve (n = 22), ventricular septal
      defect (n = 19), and pulmonary stenosis (n = 14). Preoperatively, 16 patients
      (40.0%) had complete heart block and 27 patients (67.5%) were in New York Heart
      Association functional classes III and IV. The early mortality was 10.0% (n = 4)
      and 8 patients died subsequently. The principal cause of death in all 12 patients
      was systemic ventricular failure. Overall survival including early mortality was
      78.0% at 5 years and 60.7% at 10 years; survival excluding early mortality was
      86.7% at 5 years and 67.5% at 10 years. Survivorship correlated with preoperative
      systemic ventricular ejection fraction of 44% or more (p < 0.001) and later
      interval of operation (9 deaths in 15 patients before 1981 versus 3 deaths in 25
      patients subsequently) (p = 0.06). There were no cases of surgically induced
      complete heart block. Two patients underwent late reoperations related to the
      systemic atrioventricular valve prosthesis. Follow-up extended to 26.0 years
      (median 4.7 years). At last follow-up, 18 of the 28 survivors were in New York
      Heart Association functional class I, 9 were in class II, and 1 was in class III.
      We conclude that the results of systemic atrioventricular valve replacement in
      corrected transposition have improved significantly during the past decade. To
      preserve systemic ventricular function, we suggest operation be considered at the
      earliest sign of progressive ventricular dysfunction as assessed by serial
      clinical evaluation and echocardiography.

PMID- 7715213
TI  - Surgical management of neonatal coarctation.
AB  - Between 1983 and 1994, 307 consecutive neonates underwent coarctation repair by a
      single surgical technique: extended end-to-end anastomosis. Mean age at operation
      was 13 +/- 8 days. Isolated coarctation was present in 95 patients (group 1), 102
      patients had associated ventricular septal defect (group 2), and 110 patients had
      associated complex intracardiac lesions (group 3). Aortic arch hypoplasia was
      present in 81% of the patients (62% in group 1 versus 85% in group 2 and 93% in
      group 3: p < 0.001). In 271 patients, the aortic arch reconstruction was
      performed via a left thoracotomy with normothermia (100% of group 1, 95% of group
      2, and 72% of group 3); in the other 36 patients, undergoing one-stage repair or
      palliation of the associated lesion, it was performed via a midline sternotomy
      during a short period of deep hypothermia and circulatory arrest (5% of group 2
      and 28% of group 3). Pulmonary artery banding was performed in 94 patients.
      Spontaneous ventricular septal defect closure was observed in 39% of the patients
      of group 2 operated on via thoracotomy. Early mortality rates in groups 1 (2%)
      and 2 (2%) were significantly lower than in group 3 (17%) (p < 0.001). There were
      29 late deaths, all related to associated cardiac lesions or their subsequent
      repair. The overall total mortality was 16.9%. In group 3 this rate was
      significantly higher in patients undergoing two-stage procedures (47%) than in
      those undergoing one-stage repair (23%) (p < 0.05). All but 14 survivors were
      followed up for a mean of 61 +/- 36 months. Actuarial survivals at 10 years were
      98% in group 1, 94% in group 2, and 60% in group 3. The recoarctation rate was
      9.8%, leading to 21 reoperations and three angioplasties without mortality.
      Patients with a more extended or severe form of aortic arch hypoplasia had a
      significantly higher risk of recoarctation (p < 0.001). Actuarial freedom from
      reoperation for recoarctation at 10 years was 93%. The findings of this study
      suggest that extended end-to-end anastomosis provides an adequate and safe repair
      of neonatal coarctation. Low recoarctation rate, owing to effective relief of the
      obstruction created by aortic arch hypoplasia and to complete resection of ductal
      tissue, freedom from major morbidity, and feasibility via both lateral and
      anterior approaches are the main advantages of the extended end-to-end
      anastomosis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7715212
TI  - The Norwood operation and subsequent Fontan operation in infants with complex
      congenital heart disease.
AB  - From April 1987 to September 1993, 60 infants underwent a Norwood operation for
      complex congenital heart disease including hypoplastic left heart syndrome (n =
      41), ventricular septal defect and subaortic stenosis with aortic arch
      interruption/severe coarctation (n = 7), complex single right ventricle with
      subaortic stenosis (n = 8), critical aortic stenosis with endocardial
      fibroelastosis (n = 2), and malaligned primum atrial septal defect with
      coarctation (n = 2). Age at operation ranged from 1 day to 3.9 months (mean 9
      days, median 3.5 days). The operative mortality (< 30 days) was 33% (20
      patients). Late mortality was 17% (10 patients). Nine of the 20 (45%) operative
      deaths occurred during the first 2 days after the operation as a result of sudden
      hemodynamic instability. All four infants with premature closure of the foramen
      ovale had pulmonary lymphangiectasia and died of pulmonary failure. Seven
      operative deaths have occurred in 36 patients since 1990 (19%); in the past 2
      years, no operative deaths have occurred in 22 patients. Overall, there are 30
      long-term survivors (50%). Twenty-one of these 30 infants have undergone a two
      stage repair with a modified Fontan operation at 7.3 to 27.6 months of age (mean
      18.1 months) with no mortality. Six patients have entered a three-stage repair
      strategy by undergoing a hemi-Fontan procedure at 6.8 to 23.0 months (mean 8.8
      months) with no mortality, and two of these patients have now had their modified
      Fontan operation at 23.0 to 46.7 months of age with no mortality (four are still
      awaiting surgery). Two patients have undergone a two-ventricle repair with a
      Rastelli procedure, with no mortality at 7.4 and 14.1 months of age. Early in our
      experience, infants undergoing the Norwood operation had a high early mortality
      most often related to sudden hemodynamic instability. After we instituted a
      protocol that adds carbon dioxide to the inspired gas during postoperative
      mechanical ventilation, the postoperative course became more stable and there
      have been no operative deaths. In summary, the operative mortality for the
      Norwood operation continues to improve. A subsequent Fontan operation can be
      performed with excellent clinical results.

PMID- 7715214
TI  - Early outcome of mitral valve reconstruction in patients with end-stage
      cardiomyopathy.
AB  - Uncontrollable severe mitral regurgitation is a frequent complication of end
      stage cardiomyopathy, significantly contributing to heart failure in these
      patients, and predicts a poor survival. Although elimination of mitral valve
      regurgitation could be most beneficial in this group, corrective mitral valve
      surgery has not been routinely undertaken in these very ill patients because of
      the presumed prohibitive operative mortality. We studied the early outcome of
      mitral valve reconstruction in 16 consecutive patients with cardiomyopathy and
      severe, refractory mitral regurgitation operated on between June 1993 and April
      1994. There were 11 men and five women, aged 44 to 78 years (64 +/- 8 years) with
      left ventricular ejection fractions of 9% to 25% (16% +/- 5%). Preoperatively all
      patients were in New York Heart Association class IV, had severe mitral
      regurgitation (graded 0 to 4+ according to color flow Doppler transesophageal
      echocardiography) and two were listed for transplantation. Operatively, a
      flexible annuloplasty ring was implanted in all patients. Four patients also had
      single coronary bypass grafting for incidental coronary disease. In four patients
      the operation was performed through a right thoracotomy because of prior coronary
      bypass grafting, and four patients also underwent tricuspid valve reconstruction
      for severe tricuspid regurgitation. No patient required support with an
      intraaortic balloon pump. There were no operative or hospital deaths and mean
      hospital stay was 10 days. There were three late deaths at 2, 6, and 7 months
      after mitral valve reconstruction, and the 1-year actuarial survival has been
      75%. At a mean follow-up of 8 months, all remaining patients are in New York
      Heart Association class I or II, with a mean postoperative ejection fraction of
      25% +/- 10%. There have been no hospitalizations for congestive heart failure,
      and a decrease in medications required has been noted. For patients with
      cardiomyopathy and severe mitral regurgitation, mitral valve reconstruction as
      opposed to replacement can be accomplished with low operative and early
      mortality. Although longer term follow-up is mandatory, mitral valve
      reconstruction may allow new strategies for patients with end-stage
      cardiomyopathy and severe mitral regurgitation, yielding improvement in
      symptomatic status and survival.

PMID- 7715215
TI  - Pathogenesis of acute ischemic mitral regurgitation in three dimensions.
AB  - Changes in the geometric and intravalvular relationships between subunits of the
      ovine mitral valve were measured before and after acute posterior wall myocardial
      infarction in three dimensions by means of sonomicrometry array localization. In
      13 sheep, nine sonomicrometer transducers were attached around the mitral anulus
      and to the tip and base of each papillary muscle. Five additional transducers
      were placed on the epicardium. Snares were placed around three branches of the
      circumflex coronary artery. One to 2 weeks later, echocardiograms, dimension
      measurements, and left ventricular pressures were obtained before and after the
      coronary arteries were occluded. Data were obtained from seven sheep. Coronary
      occlusion infarcted 32% of the posterior left ventricle and produced 2 to 3+
      mitral regurgitation by Doppler color flow mapping. Multidimensional scaling of
      dimension measurements obtained from sonomicrometry transducers produced three
      dimensional spatial coordinates of each transducer location throughout the
      cardiac cycle before and after infarction and onset of mitral regurgitation.
      After posterior infarction, the mitral anulus enlarges asymmetrically along the
      posterior anulus, and the tip of the posterior papillary muscle moves 1.5 +/- 0.3
      mm closer to the posterior commissure at end-systole. The posterior papillary
      muscle also elongates 1.9 +/- 0.3 mm at end-systole. The left ventricle enlarges
      asymmetrically and ventricular torsion along the long axis changes. The
      development of postinfarction mitral regurgitation appears to be the consequence
      of multiple small changes in ventricular shape and contractile deformation and in
      the spatial relationship of mitral valvular subunits.

PMID- 7715216
TI  - Severe diastolic dysfunction after endoventriculoplasty.
AB  - Endoventriculoplasty with pericardial patch has been advocated to repair
      anteroseptal ventricular aneurysm, but not studies have reported the influence of
      this technique on diastolic left ventricular function. We have evaluated the
      changes on ventricular filling by means of pulsed Doppler recording of diastolic
      transmitral flow. Doppler analysis reveals three distinct spectral patterns: (1)
      normal, (2) inverted, and (3) restrictive. We have found an abrupt change from a
      preoperative normal to postoperative restrictive pattern in a significant
      minority of patients (8%) who underwent endoventriculoplasty. These patients had
      clinical and hemodynamic signs (New York Heart Association class, time from
      anterior myocardial infarction, left ventricular end-diastolic pressure,
      pulmonary hypertension, and mitral regurgitation) of severe impairment but no
      differences were found in ejection fraction, aneurysmal extension, or remote
      myocardial function. Moreover, after operation they had a satisfactory ejection
      fraction, a low end-diastolic volume, and an apex-base length shorter than the
      predicted value for a normal population. The presence of a postoperative
      restrictive pattern of diastolic filling is a strong predictor of 3-month
      mortality and makes the medical treatment difficult. Caution must be taken to
      perform endoventriculoplasty in patients who are severely ill, especially those
      recently affected by myocardial infarction. When the clinical conditions dictate
      the operation, a nonenthusiastic volume reduction seems to be a prudent option.

PMID- 7715217
TI  - Porcine valves are reendothelialized by human recipient endothelium in vivo.
AB  - The degeneration of human allogeneic and porcine xenogeneic heart valves has not
      been clearly understood. The question is whether the observed loss of function
      and calcification is primarily an immunologic process or a mechanical process or
      is influenced by both factors. In the current study, we looked at explanted
      xenogeneic heart valves for the presence of recipient endothelium. Explanted
      valves were shock frozen and stored at -80 degrees C before use. They were
      subsequently examined by immunohistochemical staining with a variety of
      monoclonal antibodies. Xenogeneic valves showed clearly positive results for the
      human major histocompatibility complex class I and class II antigens and
      morphologically showed a thin layer of viable endothelium restricted to the
      annular region of the valve. Additionally, they were also positive for
      intercellular adhesion molecule-1 and the H-Y antigen. Although the xenogeneic
      valves were significantly degenerated, the endothelium was clearly defined and
      could be identified immunohistochemically as being of recipient origin. The
      grafts remained negative for endothelial cell-leukocyte adhesion molecule-1 and
      factor VIII. These data allow speculation on whether reendothelialization of
      valvular grafts with recipient endothelium is a normal repair mechanism in vivo.

PMID- 7715218
TI  - Comparison among arterial grafts and coronary artery. An attempt at functional
      classification.
AB  - Various arterial conduits have been used for coronary artery bypass grafting.
      However, arterial grafts are not uniform either in anatomy or in function. Some
      conduits are more spastic than others and there may be possible differences in
      long-term patency rates. The diverse biologic characteristics promote a necessity
      of classification of arterial grafts, which may facilitate the understanding of
      surgeons of biologic characteristics of various arterial grafts and provide a
      scientific basis for searching for new grafts. Another important issue is the
      comparison of reactivity between arterial grafts and coronary arteries. In this
      study, we aim to compare the pharmacologic reactivity among the human arteries
      (grafts and coronary arteries) and to classify arterial grafts. Segments of three
      arterial grafts (gastroepiploic, internal mammary, and inferior epigastric) taken
      from patients undergoing coronary artery bypass grafting and coronary arteries
      taken from explanted hearts were studied in organ baths for the contraction to
      four vasoconstrictors (endothelin-1, thromboxane A2 mimetic U46619, full
      adrenoceptor agonist norepinephrine, and depolarizing agent potassium) under
      physiologic pressure. The diameter of the four arteries at a pressure of 100 mm
      Hg was similar (p > 0.05). However, the gastroepiploic artery contracted to
      higher forces (9.41 +/- 2.0 gm for endothelin, 11.79 +/- 1.85 gm for U46619,
      13.54 +/- 2.7 gm for norepinephrine, and 11.11 +/- 1.97 gm for potassium) than
      did the coronary artery and internal mammary artery (p < 0.05) for all the tested
      vasoconstrictors and higher than the inferior epigastric artery for potassium and
      norepinephrine (p < 0.05). There was no significant difference among the other
      three arteries (internal mammary artery, inferior epigastric artery, and coronary
      artery) regarding the maximal contraction force to any vasoconstrictor. No
      difference was detected in regard to the sensitivity (effective concentration
      causing 50% of the maximal response) to the vasoconstrictors among the four
      arteries. This study reveals that among the arterial grafts and the coronary
      artery, the gastroepiploic artery has the highest contractility to various
      vasoconstrictors. On the basis of our findings and physiologic and embryologic
      knowledge we propose a classification for arterial grafts: type I (somatic
      arteries), type II (splanchnic arteries), and type III (limb arteries). Types II
      and III are prone to spasm because of higher contractility whereas type I
      arteries are usually less spastic. This classification may have important
      clinical implications for the understanding of arterial graft spasm or patency
      and may be useful in the search for new grafts.

PMID- 7715219
TI  - Direct gene transfer into donor hearts at the time of harvest.
AB  - Access to the donor heart at the time of harvest provides a unique opportunity
      for genetic manipulation of this organ before transplantation. We sought to
      determine (1) if donor mouse hearts express a foreign gene administered at
      harvest and, (2) if so, what route of gene delivery is most effective. At
      harvest, 30 micrograms of promoter cytomegalovirus-luciferase deoxyribonucleic
      plasmid in cationic liposomes was injected directly into the myocardial apex
      (group I), into the right atrium (group II), or into the coronary arteries (group
      III). The donor hearts were then transplanted into the abdomen of recipient mice
      of the same strain. The transplanted hearts were removed in 4 days and luciferase
      expression was assayed by immunohistochemistry. In group I, luciferase activity
      was localized to the apex. In group II, where plasmid was delivered into the
      right atrium, luciferase expression was detected in the right ventricle and
      sparsely in the coronary perivascular area. In group III, where plasmid was
      injected into the coronary arteries, the transplanted hearts demonstrated
      luciferase expression in (1) perivascular areas surrounding coronary arteries and
      veins, (2) coronary capillaries, and (3) the endocardia of both ventricles. This
      study suggests that (1) donor mouse hearts can be genetically modified at the
      time of harvest and (2) intracoronary infusion of plasmid yields the most
      effective method of delivery. Administration of plasmid in the coronary arteries
      localizes the expression to the endocardium and the coronary vasculature, both
      sites of immunologic interactions after heart transplantation.

PMID- 7715220
TI  - Orthotopic cardiac transplantation: a comparison of standard and bicaval
      Wythenshawe techniques.
AB  - We describe an alternative technique for orthotopic cardiac transplantation
      (bicaval Wythenshawe technique), which maintains the right and left atrial
      anatomy. We compared the new bicaval technique with the conventional (Lower and
      Shumway) technique of orthotopic cardiac transplantation to identify any
      beneficial physiologic and clinical outcomes resulting from maintaining the
      normal anatomy. Seventy-five patients were randomized on an alternate basis to
      two groups: group A (n = 40) had orthotopic cardiac transplantation with the
      bicaval technique and group B (n = 35) had conventional orthotopic heart
      transplantation. All patients were studied with transthoracic echocardiogram,
      endomyocardial biopsies, and measurement of intracardiac pressures 1, 4, and 12
      weeks after transplantation. There were no statistically significant differences
      in the demographic profile, ischemic time, bypass time, implantation time,
      transpulmonary gradient, or pulmonary vascular resistance between the two groups.
      The hemodynamic data were collected in the absence of histologic signs of
      rejection. In group A right atrial pressure (mean 3.6 mm Hg) was significantly
      lower (p < 0.03) than in group B (mean 8.8 mm Hg). The right atrial a wave was
      recorded in 38 patients in group A compared with seven patients in group B (p =
      0.041). Atrial tachyarrhythmias occurred in two patients in group A compared with
      11 in group B (p < 0.016). Temporary pacing was required in 10 patients in group
      A and 16 patients in group B (p = 0.034). Four cases of mitral regurgitation (all
      mild) were detected in group A in comparison with 12 cases (10 mild, 2 severe) in
      group B (p = 0.008). The mean ejection fraction in the first week after
      transplantation was 58% in group A and 46% in group B (p = 0.5). In the first 3
      months the need for diuretics was less in group A (mean dose 80.8 mg furosemide
      daily) than in group B (mean dose 134 mg furosemide daily in the first week
      increasing to 160 mg furosemide daily). Hospital stay was shorter in group A
      (mean 23 days) than in group B (mean 27 days) (p < 0.015). There were no early
      deaths as a result of right ventricular failure in group A (n = 0/40) compared
      with four (n = 4/35; 9%) in group B (p < 0.034). This difference suggests that
      bicaval orthotopic cardiac implantation is associated with a lower right atrial
      pressure, a lower likelihood of atrial tachyarrhythmias, less need for pacing,
      less mitral incompetence, a lower diuretic dose, and a shorter hospital
      stay.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7715222
TI  - Systemic hypothermia and circulatory arrest combined with arterial perfusion of
      the superior vena cava. Effective intraoperative cerebral protection.
AB  - We have used retrograde arterial perfusion of the superior vena cava as an
      adjunct to deep hypothermia and systemic circulatory arrest for intraoperative
      cerebral protection in 43 adult patients (18 of whom were 70 years old or older).
      The indications for the use of circulatory arrest were thoracic aortic operations
      (37 patients) and atherosclerosis or calcification of the ascending aorta (6
      patients) in patients needing aortic valve or coronary operations. In all
      patients systemic hypothermia (16 degrees to 18 degrees C) was achieved with
      cardiopulmonary bypass and the systemic arterial circulation was arrested.
      Retrograde arterial perfusion of the superior vena cava was established through a
      wire-reinforced venous cannula (with a superior vena cava tourniquet) at a
      temperature of 15 degrees C. In 36 patients a separate roller pump system was
      used for the retrograde cerebral perfusion. Central venous pressure was monitored
      at 25 to 30 mm Hg; mean flow rate was 250 ml/min. Periods of circulatory arrest
      and retrograde cerebral perfusion ranged from 4 to 110 minutes (mean 38 minutes),
      and for seven patients the period of circulatory arrest was longer than 60
      minutes. Four postoperative deaths occurred, one related to stroke in a patient
      who had an aortic dissection during coronary surgery and the others related to
      noncerebral complications. Three nonfatal cerebral complications occurred,
      although all had completely resolved by late follow-up. Advantages of retrograde
      cerebral perfusion are (1) simplicity of use and avoidance of vascular trauma,
      (2) excellent exposure, (3) retrograde flow that minimizes embolization of air
      and atherosclerotic debris, and (4) effective cerebral oxygen delivery.
      Retrograde cerebral perfusion appears to be an important adjunct to hypothermia
      and circulatory arrest not only for patients undergoing operation for ascending
      aorta and aortic arch disease but also for patients with diffuse aortic
      atherosclerosis undergoing coronary or valve operations.

PMID- 7715221
TI  - Orthotopic cardiac transplantation with direct caval anastomosis: is it the
      optimal procedure?
AB  - Total excision of the right atrium with a minimal cuff of left atrium remaining
      around the four pulmonary veins, followed by direct anastomoses on venae cavae,
      has been proposed as an alternative to the standard procedure described by
      Shumway and Lower for orthotopic cardiac transplantation. To investigate whether
      this "anatomic" transplantation should be proposed as the optimal procedure, we
      prospectively randomized 78 patients having 81 procedures since 1991 into two
      groups: group I, standard transplantation (n = 40), and group II, "anatomic"
      transplantation (n = 41). The two groups were statistically similar in recipient
      age, sex, weight, disease, and status at the time of transplantation. Also
      similar were donor age, sex, weight, and drug dependency at the time of
      harvesting. All patients could be weaned from cardiopulmonary bypass with
      comparable graft ischemic times (group I, 136 +/- 46 minutes; group II, 138 +/-
      51 minutes). Immediate recovery of sinus rhythm occurred in 20 cases of group I
      and 36 cases of group II. Delayed recovery of sinus rhythm in the first
      postoperative week occurred in 15 cases of group I and 5 cases of group II.
      Persistence of atrial arrhythmia occurred in 5 cases of group I and never in
      group II. These differences were highly significant (p < 0.001). Postoperative
      hemodynamics showed a higher cardiac index at day 1 in group II (4.12 +/- 0.85
      L/min per square meter) than in group I (3.77 +/- 0.65 L/min per square meter) (p
      = 0.04). There were 13 early deaths in group I and 8 early deaths in group II.
      One death in group I was related to an acute atrioventricular block at 3 weeks
      with no evidence of cardiac rejection at histologic examination. Two patients in
      group I (5%) required definitive pacemaker implantation for prolonged sinus node
      dysfunction. Echocardiographic and Doppler studies of survivors have been
      performed 2 to 3 months after transplantation. Right atrial area was
      significantly reduced (p < 0.01) in group II (18 +/- 4.7 cm2) versus group I (24
      +/- 7 cm2), as was left atrial area (group I, 24 +/- 4.5 cm2; group II, 20 +/- 5
      cm2) (p = 0.01). Mild tricuspid regurgitation was observed in 82% of group I
      patients versus 57% of group II patients (p < 0.05), inasmuch as mitral
      regurgitation was comparable (71% in group I, 67% in group II).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7715223
TI  - Modified ultrafiltration improves cerebral metabolic recovery after circulatory
      arrest.
AB  - Modified ultrafiltration uses hemofiltration of the patient and bypass circuit
      after separation from cardiopulmonary bypass to reverse hemodilution and edema.
      This study investigated the effect of modified ultrafiltration on cerebral
      metabolic recovery after deep hypothermic circulatory arrest. Twenty-six 1-week
      old piglets (2 to 3 kg) were supported by cardiopulmonary bypass (37 degrees C)
      at 100 ml.kg-1.min-1 and cooled to 18 degrees C. Animals underwent 90 minutes of
      circulatory arrest followed by rewarming to 37 degrees C. After being weaned from
      cardiopulmonary bypass, animals were divided into three groups: controls (n =
      10); modified ultrafiltration for 20 minutes (n = 9); transfusion of
      hemoconcentrated blood for 20 minutes (n = 7). Global cerebral blood flow was
      measured by xenon 133 clearance methods: stage I--before cardiopulmonary bypass;
      stage II--5 minutes after cardiopulmonary bypass; and stage III--25 minutes after
      cardiopulmonary bypass. Cerebral metabolic rate of oxygen consumption, cerebral
      oxygen delivery, and hematocrit value were calculated for each time point. At
      point III, the hematocrit value (percent) was elevated above baseline in the
      ultrafiltration and transfusion groups (44 +/- 1.8, 42 +/- 1.8 versus 28 +/- 1.7,
      30 +/- 0.7, respectively, p < 0.05). Cerebral oxygen delivery (ml.100 gm-1.min-1)
      increased significantly above baseline at point III after ultrafiltration (4.98
      +/- 0.32 versus 3.85 +/- 0.16, p < 0.05) or transfusion (4.59 +/- 0.17 versus
      3.89 +/- 0.06, p < 0.05) and decreased below baseline in the control group (2.77
      +/- 0.19 versus 3.81 +/- 0.16, p < 0.05). Ninety minutes of deep hypothermic
      circulatory arrest resulted in impaired cerebral metabolic oxygen consumption
      (ml.100 gm-1.min-1) at point III in the control group (1.95 +/- 0.15 versus 2.47
      +/- 0.07, p < 0.05) and transfusion group (1.72 +/- 0.10 versus 2.39 +/- 0.15, p
      < 0.05). After modified ultrafiltration, however, cerebral metabolic oxygen
      consumption at point III had increased significantly from baseline (3.12 +/- 0.24
      versus 2.48 +/- 0.13, p < 0.05), indicating that the decrease in cerebral
      metabolism immediately after deep hypothermic circulatory arrest is reversible
      and may not represent permanent cerebral injury. Use of modified ultrafiltration
      after cardiopulmonary bypass may reduce brain injury associated with deep
      hypothermic circulatory arrest.

PMID- 7715224
TI  - Accelerated recovery of postischemic stunned myocardium after induced expression
      of myocardial heat-shock protein (HSP70).
AB  - In vitro studies suggest that interventions targeted at myocardial gene
      regulation of endogenous cytoprotective elements, such as heat-shock protein, may
      attenuate myocardial ischemic injury. We tested the hypothesis that heat shock
      induced expression of myocardial heat-shock protein before ischemia accelerates
      functional recovery of postischemic stunned myocardium in the intact circulation.
      Sixteen dogs underwent partial femoral arteriovenous bypass and core temperature
      was raised to 42 degrees C for 15 minutes in eight dogs (heat-shocked) and
      maintained at 37 degrees C in eight dogs (nonheat-shocked). After 24 hours dogs
      were studied to measure myocardial segment length in the circumflex artery region
      with ultrasonic dimension transducers, left ventricular pressure with a
      micromanometer, and circumflex coronary flow with an ultrasonic probe. Regional
      contractile function was quantified by the area beneath the linear preload
      recruitable stroke work relationship at baseline and at intervals during
      reperfusion after a 15-minute circumflex artery occlusion followed by 3 hours of
      reperfusion. Baseline and peak reperfusion hyperemic circumflex flows were 37 +/-
      9 ml/min and 154 +/- 33 ml/min, respectively, in heat-shocked dogs (p < 0.001)
      and 46 +/- 24 ml/min and 171 +/- 57 ml/min, respectively, in nonheat-shocked dogs
      (p < 0.001), with no differences between groups (p = not significant) at any time
      during reperfusion. Heart rate and left ventricular peak pressure, end-diastolic
      pressure, and first derivative of left ventricular pressure were similar (all p =
      not significant) in heat-shocked and nonheat-shocked dogs during ischemia and
      reperfusion. Before ischemia, preload recruitable stroke work relationship did
      not differ (p = not significant) in heat-shocked and nonheat-shocked dogs.
      Ischemia reduced preload recruitable stroke work relationship to 32% +/- 8%
      control (p < 0.001) in heat-shocked dogs and to 19% +/- 15% control in nonheat
      shocked dogs (p < 0.001) at 15 minutes of reperfusion, indicating a similar (p =
      not significant) initial degree of injury. During 3 hours of reperfusion, preload
      recruitable stroke work relationship returned to 80% +/- 38% control in heat
      shocked dogs but to only 33% +/- 13% control in nonheat-shocked dogs (p <
      0.0001). Myocardial expression of heat-shock protein, quantified by optical
      densitometry of Western blots using an antibody specific for HSP70, was greater
      in heat-shocked than in nonheat-shocked dogs (108 +/- 27 versus 71 +/- 14
      densitometry units, p < 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7715225
TI  - Reversal of heparin anticoagulation by recombinant platelet factor 4 and
      protamine sulfate in baboons during cardiopulmonary bypass.
AB  - The ability of recombinant platelet factor 4 and protamine to neutralize heparin
      after cardiopulmonary bypass was compared in anesthestized baboons. Clotting
      titration curves of heparinized baboon blood demonstrate an anticoagulant effect
      of protamine that is not seen with recombinant platelet factor 4. Neither drug
      caused meaningful changes in central pressures or cardiac output within 30
      minutes after injection. After 30 minutes of cardiopulmonary bypass, recombinant
      platelet factor 4 normalized thrombin times and activated partial thromboplastin
      times within minutes of injection, but protamine did not. Neither drug altered
      bleeding times. Recombinant platelet factor 4 caused a species-specific
      leukopenia in baboons and significantly increased activated complement protein 3
      (C3a) more than protamine. However, the increase in plasma C3a was small and
      neither drug caused a significant increase in plasma neutrophil elastase-alpha 1
      proteinase inhibitor complex. We conclude that recombinant platelet factor 4 is
      effective and safe in baboons, does not have an anticoagulant effect with excess
      concentration, and reverses in vivo heparin more rapidly than protamine. The data
      support progression to a clinical trial.

PMID- 7715226
TI  - Regional cerebral tissue blood flow measured by the colored microsphere method
      during retrograde cerebral perfusion.
AB  - Brain tissue blood flow was measured precisely by the colored microsphere method
      during retrograde cerebral perfusion in 10 normothermic mongrel dogs. The average
      tissue blood flow rates to the cerebral cortex, cerebral medulla, brain stem,
      cerebellum, and spinal cord during retrograde cerebral perfusion at 25 mm Hg of
      external jugular venous pressure were 10.5 +/- 10.3, 4.2 +/- 4.6, 11.1 +/- 9.8,
      12.3 +/- 8.6, and 9.1 +/- 5.8 ml/min per 100 gm, respectively. The brain was
      perfused wholly by retrograde cerebral perfusion without lateralization. Total
      cerebral blood flow was calculated as the sum total rates of blood flow to each
      area. Total cerebral blood flow during retrograde cerebral perfusion at 25 mm Hg
      was 7.8 +/- 4.4 ml/min, which represented 3.5% +/- 1.9% of whole body blood flow
      and one third of the total cerebral blood flow (28.0 +/- 4.2 ml/min) during
      cardiopulmonary bypass at a flow rate of 1000 ml/min. Oxygen consumption and
      carbon dioxide elimination by the total cerebrum during retrograde cerebral
      perfusion at 25 mm Hg were 0.54 +/- 0.23 ml/min and 34 +/- 15 mumol/min,
      respectively, or 8.6% +/- 3.6% and 7.0% +/- 3.1% of the corresponding whole body
      value and represented about one third of that measured during cardiopulmonary
      bypass (1.21 +/- 0.39 ml/min and 96 +/- 15 mumol/min). Total cerebral blood flow,
      total cerebral oxygen consumption, and carbon dioxide elimination increased as
      the external jugular venous pressure increased from 15 to 25 mm Hg; however, no
      further increase occurred once the external jugular venous pressure exceeded 25
      mm Hg.

PMID- 7715229
TI  - Right ventricular function evaluated by volumetric analysis during left heart
      bypass in a canine model of postischemic cardiac dysfunction.
AB  - Right ventricular function during left heart bypass was evaluated by volumetric
      analysis with a conductance catheter in 12 dogs with postischemic cardiac
      dysfunction. The conductance catheter was used to assess the volumetric status of
      the right ventricle and thereby allowed a right ventricular pressure-volume curve
      to be obtained, in which transient volume loading on the right ventricle was
      applied. The following right ventricular properties during left heart bypass were
      assessed and compared with properties measured without left heart bypass, by
      means of load-independent parameters: maximum elastance, stroke work/end
      diastolic volume relation, end-diastolic pressure/volume relation, and stroke
      work/end-diastolic pressure relation. The stroke volume derived from the
      conductance catheter and the electromagnetic flow probe showed good linear
      correlation (r2 = 0.733 to 0.975). After initiation of left heart bypass, maximum
      elastance did not change significantly, although volume intercept significantly
      increased, from 1.2 +/- 7.3 to 3.6 +/- 7.9 ml (p < 0.05). End-diastolic
      pressure/volume relation was well fitted to the exponential curve (EDP =
      e(k1.EDV+k2)) and was shifted to the right and downward during left heart bypass;
      the slope k1 significantly decreased, from 0.12 +/- 0.06 to 0.10 +/- 0.07 (p <
      0.01). Stroke work/end-diastolic volume relation and stroke work/end-diastolic
      pressure relation were closely fitted to the linear regression, and their slopes
      were significantly increased during left heart bypass, from 0.14 +/- 0.08 to 0.18
      +/- 0.08 (p < 0.05) and from 0.22 +/- 0.15 to 0.34 +/- 0.19 (p < 0.01),
      respectively. These results suggest that the decompression of the left ventricle
      and septal shifting by left heart bypass provide good diastolic compliance and
      good systolic performance because of afterload unloading of the right ventricle.
      Thus the left heart bypass improved the overall right ventricular performance,
      particularly at higher end-diastolic pressures, in dogs with postischemic cardiac
      dysfunction.

PMID- 7715227
TI  - Linear end-systolic pressure-volume relationship during pulsatile left
      ventricular bypass represents native heart function.
AB  - This study assessed whether the end-systolic pressure-volume relationship
      obtained without any interventions during pulsatile left ventricular bypass
      adequately represents native heart function. In 11 anesthetized Holstein calves,
      left ventricular pressure was measured with a micromanometer while left
      ventricular volume was simultaneously calculated from orthogonal left ventricular
      diameters measured with ultrasonic dimension transducers. End-systolic pressure
      and volume data were subjected to linear regression analysis to achieve an end
      systolic pressure-volume relationship. Data from both caval occlusions and aortic
      occlusion were used for the control end-systolic pressure-volume relationship
      (median r = 0.941, slope = 7.4 +/- 0.8 mm Hg per milliliter per 100 gm left
      ventricular weight; mean +/- standard error of the mean). During left atrial
      aortic bypass with a Pierce-Donachy pneumatic assist pump in the asynchronous
      mode, the end-systolic pressure-volume relationships were obtained without
      interventions to change ventricular loading conditions. During maximal
      ventricular unloading during full to empty pumping, termed 100%, the resulting
      narrow range of pressure and volume data did not yield highly linear end-systolic
      pressure-volume relationships (median r = 0.669, slope = 4.9 +/- 0.9 mm Hg per
      milliliter per 100 gm left ventricular weight). However, at reduced rates off
      pumping, the end-systolic pressure-volume relationships were considerably linear
      (80%, median r = 0.819; 60%, median r = 0.868; 40%, median r = 0.899). Slopes did
      not significantly differ from control values (80%, 6.9 +/- 1.1; 60%, 8.2 +/- 1.1;
      40%, 7.8 +/- 1.1). The end-systolic pressure-volume relationship obtained without
      exogenous load changes during asynchronous, pulsatile left ventricular bypass
      represents native left ventricular systolic function.

PMID- 7715230
TI  - Double-outlet right atrium with restrictive ostium primum and incomplete
      supravalvular ring presenting as congenital mitral valve stenosis.

PMID- 7715228
TI  - Intermittent antegrade warm cardioplegia reduces oxidative stress and improves
      metabolism of the ischemic-reperfused human myocardium.
AB  - The aim of this study was to compare the effect of intermittent antegrade warm
      blood cardioplegia and intermittent antegrade cold blood cardioplegia on
      myocardial metabolism and free radical generation of the ischemic-reperfused
      human myocardium. Thirty patients undergoing mitral valve procedures were
      randomly allocated to two groups: group 1 (15 patients) received warm blood
      cardioplegia and group 2 (15 patients), cold blood cardioplegia. Myocardial
      metabolism was assessed before aortic clamping, 1 minute after crossclamp
      removal, and after 20 minutes of reperfusion, by collecting blood simultaneously
      from the radial artery and coronary sinus. All samples were analyzed for lactate,
      creatine kinase, reduced and oxidized glutathione, ascorbic acid, fluorescent
      products of lipid peroxidation, and leukocyte activation (elastase). In all
      patients, early reperfusion was associated with significant coronary sinus
      lactate release. In group 2, but not in group 1, significant coronary sinus
      release of reduced and oxidized glutathione, fluorescent products of lipid
      peroxidation, and creatine kinase was also found; moreover, arterial-coronary
      sinus difference of ascorbic acid content was increased only in group 2,
      suggesting a transmyocardial consumption of this antioxidant vitamin. After 20
      minutes of reperfusion, coronary sinus lactate release was no longer present in
      group 1, whereas significant production was still evident in group 2. In this
      group, significant coronary sinus release of fluorescent products of
      lipoperoxidation and reduced and oxidized glutathione was also observed at this
      time. No significant release of elastase from the coronary sinus was noted in the
      two groups throughout the study. The left ventricular stroke work index measured
      at the end of the study indicated a better functional recovery in group 1 than in
      group 2. In conclusion, intermittent antegrade warm blood cardioplegia protects
      the myocardium from ischemia-reperfusion injury better than intermittent
      antegrade cold blood cardioplegia; this phenomenon may be partly due to the
      decreased tissue oxidant burden mediated by intermittent warm blood cardioplegia.

PMID- 7715231
TI  - Congenital total absence of the pericardium: case report of a 72-year-old man and
      review of the literature.

PMID- 7715232
TI  - Intentional delayed repair of acute dissection of the ascending aorta complicated
      by stroke.

PMID- 7715234
TI  - Biophysics of pulsatile perfusion.

PMID- 7715233
TI  - Effect of recombinant erythropoietin on peripheral T lymphocytes.

PMID- 7715235
TI  - Is left heart bypass by cannulation of both femoral arteries an effective form of
      assisted circulation?

PMID- 7715236
TI  - Evaluating the impact of magnetic resonance imaging on patients with operable non
      small-cell lung cancer and unilateral adrenal masses: importance of appropriate
      technique.

PMID- 7715237
TI  - Bidirectional inferior vena cava-pulmonary artery shunt.

PMID- 7715238
TI  - Retransplantation in heart-lung recipients with obliterative bronchiolitis.

PMID- 7715239
TI  - Aortic and aortic-mitral annular enlargement.

PMID- 7715240
TI  - Animal models for studying transport across the blood-brain barrier.
AB  - There are many reasons for wishing to determine the rate of uptake of a drug from
      blood into brain parenchyma. However, when faced with doing so for the first
      time, choosing a method can be a formidable task. There are at least 7 methods
      from which to choose: indicator dilution, brain uptake index, microdialysis,
      external registration, PET scanning, in situ perfusion, and compartmental
      modeling. Each method has advantages and disadvantages. Some methods require very
      little equipment while others require equipment that can cost millions of
      dollars. Some methods require very little technical experience whereas others
      require complex surgical manipulation. The mathematics alone for the various
      methods range from simple algebra to complex integral calculus and differential
      equations. Like most things in science, as the complexity of the technique
      increases, so does the quantity of information it provides. This review is meant
      to serve as a starting point for the researcher who wishes to study transport and
      uptake across the blood-brain barrier in animal models. An overview of the
      mathematical theory, as well as an introduction to the techniques, is presented.

PMID- 7715242
TI  - Regional differences in the extent of RNA editing of the glutamate receptor
      subunits GluR2 and GluR6 in rat brain.
AB  - The extent of RNA editing of the glutamate receptor subunits GluR2 and GluR6 was
      studied by using a newly developed method based on the restriction analysis of
      the subunit-specific polymerase chain reaction (PCR) product with the enzyme Bbv
      1. Total RNA was isolated from following brain regions: cortex, striatum,
      hippocampus, thalamus, hypothalamus, cerebellum, pons/medulla oblongata and white
      matter. RNA was transcribed into cDNA, which was used as template for PCR. PCR
      was run with GluR2- and GluR6-specific primers to amplify a product across the
      edited region. The PCR products were analysed with the restriction enzyme Bbv 1
      and gel electrophoresis of the restriction digest. Bbv 1 recognizes the sequence
      GCAGC which is identical with the sequence of the PCR product originating from
      unedited GluR2 or GluR6 mRNA. Thus, this enzyme splits the non-edited PCR product
      into two fragments while leaving the edited PCR product intact. After
      electrophoresis of the restriction digest and photographing gels, optical density
      of bands was quantified with image analysis. For quantification calibration
      curves were made with PCR products from constructs originating from edited and
      non-edited GluR6 mRNA. GluR2 mRNA was completely edited in all brain structures
      studied. Editing of GluR6 mRNA, in contrast, was high in gray matter structures
      (above 90%) but considerably lower in the pons/medulla oblongata (66%) and white
      matter (55%). It is, therefore, suggested that editing of GluR2 and GluR6 mRNA is
      performed by different enzymatic activities. Studying RNA editing of glutamate
      receptor subunits will extend knowledge about the role of calcium fluxes through
      non-NMDA glutamate receptor ion channels.

PMID- 7715241
TI  - Photic responses of the lateral geniculate nucleus can be used as a stereotaxic
      guide for micropipette placement.
AB  - Neuroanatomical studies of the cat's thalamus require accurate placement of a
      micropipette for tracer injections. In order to determine interanimal
      differences, we describe a simple method which compares the location of the
      different laminae of the dorsal lateral geniculate nucleus (LGNd) with a
      stereotaxic atlas. The visual electrophysiological response to a flash was
      recorded from the LGNd with an enamelled stainless-steel electrode. The response
      steadily increased in amplitude through the optic radiation, lamina A and lamina
      A1. Further penetration through the LGNd resulted in the reversal of the recorded
      potential. The reversal point was lesioned and found to lie between lamina A1 and
      lamina C. Based on the dorsal level of laminae A, A1 and C as determined by the
      reversal point, these estimates of LGNd location can be compared with a
      stereotaxic atlas and corrections made to subsequent placement of micropipettes
      used for injections in other thalamic structures.

PMID- 7715243
TI  - An intact nerve preparation for monitoring inputs from single joint afferent
      fibres.
AB  - A preparation is described that permits the monitoring of activity from
      individual joint afferent nerve fibres in an intact peripheral nerve of the cat.
      The joint nerve used was the medial articular nerve (MAN) that supplies the
      medial and anteromedial aspects of the knee joint. This nerve is sufficiently
      fine that if freed from nearby tissue over a length of 2-5 cm and placed over a
      platinum hook electrode it is possible to identify and monitor, from the intact
      nerve, the impulse activity from each group II joint afferent fibre activated by
      mechanical stimulation of the joint capsule. The signal-to-noise ratio exceeds
      5:1 and in most cases was approximately 10:1. With this preparation it is now
      possible to examine the central actions and security of transmission at central
      synaptic targets for single, identified group II joint afferent fibres.

PMID- 7715244
TI  - The measurement of ionic conductivities and mobilities of certain less common
      organic ions needed for junction potential corrections in electrophysiology.
AB  - Junction potential corrections are often required in electrophysiological
      measurements, particularly when using the patch-clamp technique. The ionic
      conductivities and mobilities of certain less common organic ions were measured
      for use in junction potential corrections in electrophysiological measurements.
      The mobilities of these ions relative to K+ were: aspartate (0.30), choline
      (0.51), gluconate (0.33), glutamate (0.26), HEPES (0.30), isethionate (0.52), MES
      (0.37), MOPS (0.35), N-methyl-D-glucamine (0.33), and Tris (0.40). In addition,
      junction potentials were directly measured for a number of typical simplified
      patch-clamp solutions containing these ions. The measured junction potentials
      generally agreed well with the values calculated using the Generalized Henderson
      Equation with the appropriate ionic mobility. The accuracy of the measurements is
      discussed.

PMID- 7715245
TI  - Application of polynomial regression modeling to automatic measurement of periods
      of EMG activity.
AB  - We have developed a new algorithm for automatic detection and measurement of
      on/off periods of EMG burst and examined validity and reliability of the
      measuring technique. Mean EMG amplitude (M) during a semi-stationary state of an
      EMG data array [EMG] is calculated. Because M was determined to be significantly
      correlated with g(T(on)) (or g(Tend)) which represent amplitude on a polynomial
      regression curve g(t) which best-fitted to the [EMG], the estimate ]g(T(on) (or
      g(T(end)) is calculated by substituting M into a regressive equation f(M) which
      explains the association between the M and g(T(on)) (or g(T(end)). T(on) and
      T(end) are human-determined on/off burst times for the [EMG]. The on/off periods
      of the EMG burst are finally computed as roots of the g(t) when g(T(on)) and
      g(T(end)) are subtracted from the constant of the polynomial. Application of the
      current method to the human masticatory muscle activity during chewing revealed
      that the absolute differences between human- and computer-determined measurements
      were smaller than 10 ms, and these measurements did not differ significantly. We
      conclude that the proposed algorithm is useful and effective for automatic
      detection and measurement of on/off periods of EMG burst.

PMID- 7715246
TI  - The use of the rat iris as a model system to evaluate the effect of the
      cholinotoxin, AF64A, in vivo.
AB  - The iris is innervated by both cholinergic parasympathetic, and adrenergic
      sympathetic branches of the autonomic nervous system. This innervation represents
      a simple and anatomically well-defined system to evaluate the effects of chemical
      compounds on cholinergic and adrenergic neurons. AF64A (acetyl ethylcholine
      aziridinium) is a known cholinotoxin in the brain and, in these experiments using
      the iris system, we evaluated its in vivo effect on cholinergic enzyme activity,
      pupillary size, and catecholamine neurotransmitter levels. We found in this
      system that AF64A reduces the activity of choline acetyltransferase (ChAT) but
      not acetylcholinesterase (AChE). AF64A is selective for cholinergic neurons,
      since norepinephrine and dopamine levels were unaffected.

PMID- 7715247
TI  - A technique for the primary dissociation of neurons from restricted regions of
      the vertebrate CNS.
AB  - Acute isolation of vertebrate neurons has been used extensively to characterize
      membrane properties in the absence of circuit connections or extensive dendritic
      arborizations. We describe a technique that allows cells to be dissociated from
      anatomically defined regions of a tissue slice at a resolution beyond that
      attainable by micro-dissection. Dissociation is performed by using a fire
      polished electrode with a tip diameter of 40-100 microns connected by tubing to a
      micrometer syringe that allows graded levels of positive or negative pressure to
      be applied at the electrode tip. The electrode tip is placed under microscopic
      observation upon a cell group within an enzymatically treated slice and negative
      pressure is applied to dissociate cells into the electrode shaft. Positive
      pressure is used to eject the cells onto the surface of poly-L-lysine-coated
      glass coverslips. We have used this technique to dissociate and culture cells
      from specific laminae of separate sensory maps in a medullary nucleus of adult
      weakly electric fish. Isolated cells were viable, could be identified by
      morphological criteria, and exhibited process extension within 2 h of plating.
      This technique greatly increases the probability of isolating morphologically
      identifiable vertebrate neurons for electrophysiological analysis or for the
      reconstruction of neural circuits in vitro.

PMID- 7715248
TI  - Neuroanatomical tract tracing provides histological verification of neuron loss
      following cytotoxic lesions.
AB  - In the present study we report a neuroanatomical procedure that provides direct
      histological verification of the extent of neuron loss following cytotoxic
      lesions of the lateral subdivision of the habenular complex (Lhb). Following
      kainic acid-induced lesions of Lhb neurons, the fluorescent retrograde tracer
      Fluoro-Gold was injected into the ventral midbrain where many medial habenula
      (Mhb) and Lhb neurons project. The absence of retrogradely labeled neurons in the
      Lhb indicated the extent of neuron loss there, and the presence of Fluoro-Gold
      labeled neurons in the Mhb indicated that its neurons were intact. The extent of
      neuron loss in the Lhb was significantly correlated with behavioral data.
      Retrograde tract tracing can be used as an effective histological tool to verify
      the extent of neuron loss following a lesion procedure.

PMID- 7715249
TI  - Automating the quantitative analysis of 2-D neural dendritic trees.
AB  - Neurons in the central and peripheral nervous system vary widely in their
      dendritic branching patterns. Quantification of the morphological characteristics
      used to identify different classes of neurons and relate neural structure to
      function requires that accurate metric and non-metric data be obtained from
      neural images obtained by camera-lucida drawing or from digitized video images
      made with transmitted, fluorescence or confocal microscopy. This paper describes
      a largely automated procedure for determining the dendritic tree structure of
      largely planar cells (such as retinal ganglion cells or cells in tissue culture
      monolayers) from an initial pictorial representation or digitized image. From
      this structure, non-metric data (such as the ordered 'tree' of branches) and
      metric information (such as total dendritic length and dendritic field area) can
      be automatically computed. The use of this method is specifically illustrated in
      the capture of the dendritic tree structure of retinal ganglion cells from the
      rabbit retina.

PMID- 7715250
TI  - Quantitation of dopaminergic neurons in 3-dimensional reaggregate tissue culture
      by computer-assisted image analysis.
AB  - Three-dimensional (3D) reaggregate tissue culture provides a means of
      quantitatively assessing neuronal cell survival under a variety of experimental
      conditions. A method is presented for estimation of, and comparison between, the
      total numbers of cells of a given neurochemical type within individual
      experimental flasks. The method involves cell counting from random reaggregate
      sections, determination of sectional volumes, and of 3D reaggregate volumes by a
      novel image-analysis computer system.

PMID- 7715251
TI  - Gabor filters: an informative way for analysing event-related brain activity.
AB  - Frequency-specific, i.e., narrow-band brain, activity is traditionally analyzed
      on the basis of either a time- or frequency-domain representation of the signal.
      Here we demonstrate an alternative method based on Gabor functions which are well
      known for their optimal concentration in time and frequency. Using Gabor
      filtering, amplitude and frequency information can be separated clearly from one
      another and certain novel approaches to averaging become possible.

PMID- 7715252
TI  - The effect of anesthesia on abdominal muscle resting length and shortening in
      awake dogs.
AB  - The objectives of this study were to examine the effects of anesthesia and
      implantation of sonomicrometer transducers on tonic and phasic expiratory
      activity of the abdominal muscles. Eight tracheotomized dogs were chronically
      instrumented with sonomicrometer transducers placed in each of the four abdominal
      muscles. The dogs were studied in the lateral decubitus position immediately
      after transducer implantation, while under halothane anesthesia, and then in the
      awake dogs 2 to 3 days postimplantation, and repeatedly over a 2- to 8-week
      period. The resting length (LRL) of the rectus abdominis (RA) was reduced in the
      first awake study compared to during anesthesia, but there was no change in LRL
      of the other abdominal muscles. The abdominal muscles phasically, actively,
      shortened during expiration more in the awake state than in the anesthetized
      state. The internal abdominal muscle layer (transversus abdominis and internal
      oblique) shortened phasically more than the external layer (RA and external
      oblique). Neither the LRL nor the amount of phasic shortening of the abdominal
      muscles changed significantly over the period in which transducers were in situ
      (2-8 weeks). Muscle sections excised at the end of each study exhibited small
      capsules of fibrosis immediately surrounding the transducers with normal muscle
      tissue between pairs of transducers. In conclusion, both tonic and phasic
      respiratory activity of the abdominal muscles, reflected by changes in resting
      length and the amount of active shortening, respectively, were absent during
      halothane anaesthesia and chronic implantation of sonomicrometer transducers per
      se had no effect.

PMID- 7715253
TI  - Obstructive sleep apnea syndrome and bronchial hyperreactivity.
AB  - This study was designed to investigate the prevalence of bronchial
      hyperreactivity (BH) in patients with obstructive sleep apnea syndrome (OSAS),
      heavy snorers, and light snorers; its correlation with OSAS severity; and its
      response to nasal CPAP therapy. Forty-eight age- and sex-matched subjects were
      selected on the basis of preentry sleep studies: Group I consisted of 16 patients
      with OSAS (hypopnea-apnea index (HAI) = 35 +/- 9); group II consisted of 16 cases
      of heavy snorers without OSAS; and group III, a control group, consisted of 16
      subjects with only mild snoring. All 48 patients had normal pulmonary function
      (simple spirometry) prior to study entry and had no history of asthma or
      allergies. The prevalence of BH was prospectively assessed by giving each subject
      a methacholine challenge test (MCT). Patients with a positive MCT were treated
      with 2-3 months of nasal CPAP treatment, after which they had a second MCT. Four
      of 16 patients in group I had BH on MCT (PD20 = 88, 103, 109, 162 D.U.), whereas
      none of the group II or III subjects demonstrated BH. There was no correlation
      between BH and the severity of the OSAS. The 4 patients with BH in group I showed
      an increase in PD20M after 2-3 months of nasal CPAP treatment. In conclusion, BH
      may occur in patients with OSAS. It is unrelated to the severity of the OSAS, and
      nasal constant positive airway pressure (CPAP) therapy can decrease the
      hyperreactivity to methacholine in these patients.

PMID- 7715254
TI  - Induction of MHC class II antigens on rat bronchial epithelial cells by
      interferon-gamma and its effect on antigen presentation.
AB  - Recent studies have found aberrant expression of class II antigens by bronchial
      epithelial cells (BECs), suggesting that these cells may also be involved in
      airway mucosal immunity. However, the regulation of class II antigen expression
      on BECs by cytokines and the functional capacity of such cells bearing class II
      molecules remain unknown. We investigated the effect of IFN-gamma on class II
      antigen expression by cultured rat BECs, as well as the ability of these cells to
      present intact protein antigens to specifically sensitized T cells. Although
      primary BECs did not express class II antigens, IFN-gamma readily induced their
      expression in a dose-dependent manner. More than 85% of the BECs treated with
      1000 U/ml of IFN-gamma were positive for class II antigens. In addition, when IFN
      treated BECs bearing class II molecules were pulsed with ovalbumin (OVA), they
      significantly stimulated the proliferation of OVA-sensitized T cells, whereas
      cells that were not treated with IFN-gamma but were pulsed with OVA did not do
      so. Our findings indicate that BECs bearing class II molecules are capable of
      presenting OVA to OVA-sensitized T cells. These results suggest that various
      pathological conditions causing the local production of IFN-gamma may increase
      class II antigen expression on BECs, which in turn may modulate the airway
      mucosal immune response by the presentation of antigens to T cells.

PMID- 7715255
TI  - Glucocorticoid-induced down regulation of transforming growth factor-beta 1 in
      adult rat lung fibroblasts.
AB  - Transforming growth factor-beta 1 mRNA and transforming growth factor beta
      activity are decreased with exposure of normal adult rat lung fibroblasts to
      dexamethasone. Dexamethasone caused a decrease in transforming growth factor-beta
      1 mRNA within 2 hours, which was sustained at least over a 24-hour period. The
      decrease in transforming growth factor-beta 1 mRNA was dose related.
      Dexamethasone treatment of rat lung fibroblasts also resulted in a decrease of
      transforming growth factor beta activity as determined by the mink lung cell
      growth inhibition assay. These data indicate that glucocorticoids may regulate
      collagen synthesis at least in part through the mediation of transforming growth
      factor-beta 1 in rat lung fibroblasts.

PMID- 7715256
TI  - Platelet-activating factor stimulates eicosanoid production in cultured feline
      tracheal epithelial cells.
AB  - The effect of platelet-activating factor (PAF) on eicosanoid generation and
      release in cultured feline tracheal epithelial cells was investigated by
      measuring a wide range of lipoxygenase and cyclooxygenase pathway products.
      Subconfluent epithelial cell cultures were stimulated by PAF and eicosanoid
      production was determined by high performance liquid chromatography (HPLC) of
      [3H]-labeled arachidonic acid (AA) metabolites and by radioimmunoassay (RIA)
      following HPLC separation. The HPLC chromatograms revealed that PAF augmented the
      release of prostaglandin (PG)E2, PGF2 alpha, 12-hydroxyeicosatetraenoic acid
      (HETE), and AA. Among these eicosanoids, PGE2 predominated under baseline
      conditions and following PAF exposure. RIAs of the nonradiolabeled HPLC elution
      corresponding to various eicosanoid standards demonstrated that PAF increased the
      production of 6-keto-PGF1 alpha, thromboxane B2 (TXB2), PGD2, 5-HETE, and 15
      HETE, as well as PGE2, PGF2 alpha, and 12-HETE. The PAF-induced eicosanoid
      augmentation was dose-dependent and occurred within 1 hour with a prompt decline
      following termination of PAF exposure. This stimulating effect of PAF on
      eicosanoid release was blocked by two PAF receptor antagonists, Ro 19-3704 and
      WEB 2086. The PAF-induced increase in eicosanoid release was similar in magnitude
      to the increase caused by calcium ionophore (Ca-ionophore) A23187, a potent known
      stimulus for eicosanoid release. Cells of different culture durations (3 and 6
      days) showed similar capacity for eicosanoid production. We conclude that PAF
      stimulates the production of cyclooxygenase and lipoxygenase pathway products
      from airway epithelial cells via PAF receptors, and that these epithelium-derived
      eicosanoids may be responsible for some of the PAF-induced respiratory
      physiological and pathophysiological effects.

PMID- 7715257
TI  - [Minimal residual disease in chronic myeloid leukemia in patients with long
      survival after allogeneic bone marrow transplantation].
AB  - BACKGROUND: The study of the minimum residual disease in a series of patients
      diagnosed with chronic myeloid leukemia (CML) treated with non manipulated
      allogeneic bone marrow transplantation (BMT) reporting a survival longer than 6
      months is presented. METHODS: The positivity of the chimeric transcription bcr
      abl was studied in 18 long surviving BMT patients. The complementary DNA (cDNA)
      corresponding to this transcription was amplified by the polymerase chain
      reaction (PCR) technique. Double internal PCR (PCR nested) was performed to
      increase the sensitivity of the determination. RESULTS: The first determination
      was performed in different post BMT stages with a median of 27 months (4-97).
      Fourteen out the 18 patients were positive for the bcr-abl transcription. On the
      second determination carried out in 11 cases with a sample obtained 24 months
      after the first 7 out of the 10 positive cases evaluated presented an identical
      pattern while the patient who originally was negative, remained so. The original
      transcription became negative in three patients. Only one of the positive cases
      developed hematologic relapse during the study period. CONCLUSIONS: Aggressive
      chemo-radiotherapy does not eradicate the leukemic clone in all patients with
      chronic myeloid leukemia. The persistence of positive results in a high number of
      patients with chronic myeloid leukemia in remission for over 6 months after bone
      marrow transplantation is not predictive of imminent relapse.

PMID- 7715258
TI  - [Influence of the intravenous nitroglycerin dose on the appearance of drug
      tolerance].
AB  - BACKGROUND: There are few studies on the influence of different doses of
      intravenous nitroglycerin (NTG) on the appearance of drug tolerance. METHODS: A
      controlled clinical trial was performed in 40 patients admitted to an ICU with
      the diagnosis of acute myocardial infarction (AMI). The patients were divided
      into two groups: group A with a continuous perfusion of NTG at 2 mg/h, and group
      B with 4 mg/h. At 30 minutes of the infusion, NTG was exchanged for a placebo in
      half of the patients of each group (subgroups A1 and B1) with the remaining
      patients continuing with NTG for 24 h (A2 and B2). The hemodynamic variables
      studied were central venous pressure (CVP), pulmonary capillary pressure (PCP),
      mean pulmonary artery pressure (PAP) and mean blood pressure (BP). RESULTS: The
      patients in group A showed a decrease in the hemodynamic effects in all the
      variables studied. At 24 h of infusion no differences were observed with respect
      to the previous NTG values for CVP and PCP, with significant differences being
      maintained for PAP and BP. In group B the hemodynamic effect was maintained for
      all the variables during the 24 hours studied. CONCLUSIONS: In patients with
      acute myocardial infarction, the dosis of nitroglycerin administered was found to
      have a determined influence in the appearance of drug tolerance with this fact
      being more evident on evaluation of the effect of nitroglycerin on the venous
      system.

PMID- 7715261
TI  - [Necrotizing fasciitis: novelty of an old disease].

PMID- 7715260
TI  - [How can chronic myeloid leukemia be cured with bone marrow transplantation?].

PMID- 7715263
TI  - [Spanish medical specialty reviews].

PMID- 7715259
TI  - [Progression of HIV infection in a cohort of hemophiliacs over an 11-year
      period].
AB  - BACKGROUND: The progression of HIV infection in a cohort of hemophiliacs was
      evaluated taking into consideration the particularities of the natural history of
      HIV in this population and comparing the same with that described for other
      series of hemophiliacs and other risk groups for HIV infection. METHODS: A cohort
      of 141 hemophiliac patients with HIV infection controlled in a Hemophilia Unit
      since January 1983 was studied. The accumulated incidence of AIDS and the
      mortality at 11 years of follow up were evaluated. Likewise, the association of
      prognostic factors such as age, type of hemophilia or previous treatment with
      antihemophilic factors were evaluated. RESULTS: The accumulated incidence of AIDS
      at the end of follow up was 56% with a mortality rate of 33%. The evolution
      showed statistically significant differences with regard to age (p = 0.00048) and
      previous treatment (p = 0.00239). No differences were observed concerning the
      type of hemophilia or its severity. CONCLUSIONS: HIV infection in the cohort of
      hemophiliacs studied presented similar accumulated AIDS incidence and mortality
      to those described in other series of hemophiliacs. These values are apparently
      more favorable than those referred for other risk groups, possibly due to the
      particular epidemiologic characteristics.

PMID- 7715262
TI  - [Pseudotumorous hyperplasia of the caudate lobe of the liver in a patient with
      Alagille syndrome].
AB  - The Alagille's syndrome consists in hypoplasia of the intrahepatic biliary ducts
      associated to congenital abnormalities of different organs. It is usually
      diagnosed in infancy due to cholestasis with good prognosis. The case of a 31
      year old women who presented prominent chin, micrognathia, flattening of the
      nasal bone, infundibular stenosis of the pulmonary artery and cholestasis is
      reported. Ultrasonography demonstrated a lesion in the space of the hepatic
      caudate lobe with punction showing sinusoidal dilatation and infiltration of some
      portal spaces by lymphocytes, eosinophils and neutrophils. Samples of liver
      tissue obtained during laparotomy showed an absence of intrahepatic biliary ducts
      in the right and left lobes and preservation of those of the caudate lobe, which
      was also increased in size with a pseudotumoral appearance. The patients was
      asymptomatic with slight anicteric cholestasis at 16 months of diagnosis. The
      rarity of these forms of Alagille's syndrome with areas free of hypoplasia of the
      intrahepatic biliary ducts are of note.

PMID- 7715264
TI  - [Human lymphotropic virus type I (HTLV-I)].

PMID- 7715265
TI  - [Pleuro-pericardial metastases of prostatic adenocarcinoma].

PMID- 7715267
TI  - [Prevalence of illicit drug consumption in an emergency service].

PMID- 7715268
TI  - [Spontaneous fracture of the sacrum of osteoporotic origin].

PMID- 7715266
TI  - [Oral Kaposi's sarcoma: role of radiotherapy].

PMID- 7715269
TI  - [Sepsis due to Pseudomonas stutzeri in a patient with acute leukemia].

PMID- 7715270
TI  - [Transitory proteinuria during treatment with tretinoin].

PMID- 7715272
TI  - [Female scientists are not treated unfairly by the MFR (Medical Research
      Committee)].

PMID- 7715271
TI  - [The bill on primary health care and private care].

PMID- 7715273
TI  - [Need for a coordinated pediatric intensive care].

PMID- 7715275
TI  - [Improve the care of heart failure].

PMID- 7715274
TI  - [The physician-nurse cooperation is satisfactory].

PMID- 7715276
TI  - [History of medicine is an important part of the medical curriculum].

PMID- 7715277
TI  - [How can the victims of sects be helped?].

PMID- 7715278
TI  - [Patient questionnaires scrutinized. Who is asking about what and for what
      purpose?].

PMID- 7715279
TI  - [Transforming growth factor-beta. An interesting candidate for clinical use].
AB  - Transforming growth factor-beta (TGF-beta) is the prototype of a large family of
      growth regulatory factors affecting the growth and differentiation of many cell
      types. Their action is mediated by complex formation of type I and type II
      receptors, both of which are serine/threonine kinases. TGF-beta inhibitors
      inhibit the growth of most cell types are potent immunosuppressive agents. They
      also stimulate the formation of connective tissue, thus promoting wound healing.
      TGF-beta and TGF-beta antagonists may have potential clinical uses in the
      treatment of various disorders.

PMID- 7715281
TI  - [Copper amalgam as recommended by the National Board of Health and Welfare].

PMID- 7715280
TI  - [WHO rehabilitation in the former Yugoslavia. Prostheses and education as part of
      a helpful project].

PMID- 7715282
TI  - [Intracoronary diagnosis in coronary angioplasty. Extended information with new
      techniques].

PMID- 7715283
TI  - [Is the patient satisfied? The KUPP (Quality from the Patient's Viewpoint)--a new
      formula for measurement of quality of health care].

PMID- 7715284
TI  - [How the addicts perceive their own therapy. A first for a written questionnaire
      at a drug treatment center].

PMID- 7715285
TI  - [Young men and old women fall most often on slippery ice and snow].

PMID- 7715286
TI  - Male reproductive health and environmental oestrogens.

PMID- 7715287
TI  - Telomerase that shapes our ends.

PMID- 7715288
TI  - The glimmer of HIV proteinase inhibitors.

PMID- 7715289
TI  - Cardiac vagal activity: a target for intervention in heart disease.

PMID- 7715290
TI  - Research by collaboration.

PMID- 7715291
TI  - Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International
      Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators.
AB  - The role of fluorouracil and folinic acid and adjuvant therapy for colon cancer
      is not clear. We undertook independently three randomised trials to find out the
      efficacy of fluorouracil and high-dose folinic acid after surgery for Dukes' B
      and C stage colon cancer. The three studies by the Gruppo Interdisciplinare
      Valutazione Interventi Oncologia (GIVIO), the National Cancer Institute Canada
      Clinical Trials Group (NCIC-CTG), and the Fondation Francaise de Cancerologie
      Digestive (FFCD) were pooled for combined analysis. Each trial was multicentre
      and used the same treatment regimen (fluorouracil 370-400 mg/m2 plus folinic acid
      200 mg/m2 daily for 5 days, every 28 days for 6 cycles). A pooled analysis of the
      results was done on the basis of a previously agreed protocol when there were
      sufficient events to detect at least a 10% reduction in mortality with 80% power.
      1526 patients with resected B (56%) and C (44%) carcinoma of the colon were
      enrolled and 1493 were confirmed as eligible. 736 were assigned to the treatment
      group and 757 to the control group. Fluorouracil/folinic acid significantly
      reduced mortality by 22% (95% CI 3-38; p = 0.029) and events by 35% (22-46; p <
      0.0001), increasing 3-year event-free survival from 62% to 71% and overall
      survival from 78% to 83%. Compliance with treatment was good; more than 80% of
      patients completed the planned treatment. Side-effects were clinically acceptable
      with only 1 treatment-related death. The commonest side-effects were
      gastrointestinal, but severe toxic effects (WHO grade 4) occurred in fewer than
      3% of cases. We conclude that fluorouracil plus high-dose folinic acid is a well
      tolerated and effective 6-month adjuvant regimen for colon cancer.

PMID- 7715292
TI  - QT dispersion and mortality after myocardial infarction.
AB  - QT dispersion may serve as a measure of variability in ventricular recovery time
      and may be a means of identifying patients at risk of arrhythmias and sudden
      death after acute myocardial infarction. We investigated this possibility on
      electrocardiograms (ECGs) recorded 2 or 3 days after infarction (early) and at
      least 4 weeks later (late). 163 patients who died between 1 day and 5 years after
      infarct were compared with an equal number of survivors matched for age and sex.
      53 of the patients who died and 82 survivors also had late ECGs. There was no
      difference in early QT dispersion between the patients who died and the survivors
      (mean QTc dispersion 112.1 [SD 44.4] vs 109.9 [42.7] ms1/2). QTc dispersion fell
      significantly from early to late ECGs in survivors (110.9 [48.5] to 76.5 [28.8]
      ms1/2), but not in patients who died during follow-up (108.0 [51.0] to 98.9
      [43.1] ms1/2). The difference between the groups in the mean change was
      significant (34.4 [55.2] vs 9.1 [60.8] ms1/2, p = 0.016). QT dispersion measured
      on an ECG recorded 2 or 3 days after acute myocardial infarction does not predict
      mortality during the next 5 years. Increased QT dispersion on ECGs recorded at
      least 4 weeks after infarct may be associated with subsequent mortality, but this
      finding must be confirmed in a prospective trial.

PMID- 7715293
TI  - Safety, immunogenicity, and efficacy of live attenuated Vibrio cholerae O139
      vaccine prototype.
AB  - New vaccines are needed to prevent cholera caused by Vibrio cholerae O139.
      Attenuated V cholerae O139 vaccines were made by deleting multiple copies of the
      cholera-toxin genetic element from two virulent strains of the organism, MO10 and
      AI4456. The deletion mutants were further modified by insertion of a construct
      that encoded the B subunit of cholera toxin, thus generating strains Bengal-3 and
      VRI-16. A stable spontaneous non-motile derivative of Bengal-3 was isolated and
      designated Bengal-15; VRI-16 is naturally non-motile. Bengal-3, Bengal-15, and
      VRI-16 were evaluated as oral single-dose cholera vaccine candidates in 4
      volunteers each, and MO10 was given to 3 volunteers. 1 of 4 volunteers who
      received Bengal-3 and all 3 who received MO10 had diarrhoea. VRI-16 caused no
      significant symptoms but was not immunogenic. Bengal-15 produced few symptoms and
      was nearly as immunogenic as MO10. Subsequently, Bengal-15 was given to 10
      volunteers at a dose of 10(8) colony-forming units. No volunteers had diarrhoea,
      and other subjective symptoms were as common in vaccinees as in 3 buffer
      recipients. 1 month after vaccination, 7 vaccinees, the 3 buffer recipients, and
      3 unimmunised subjects were challenged with 5 x 10(6) colony-forming units of V
      cholerae O139. 5 of 6 controls had cholera-like diarrhoea. By contrast, 1 of 7
      vaccinees had diarrhoea, which was mild and had a long incubation period. Vaccine
      protective efficacy was 83%. Our results indicate the Bengal-15 is a safe live
      attenuated vaccine candidate for cholera caused by the O139 serogroup.

PMID- 7715294
TI  - Safety and activity of saquinavir in HIV infection.
AB  - We evaluated saquinavir, an orally active, selective inhibitor of HIV proteinase,
      in a randomised, double-blind, dose-ranging study in 49 zidovudine-naive HIV
      positive patients with few or no symptoms and CD4 cell counts of 500 or less. The
      study was designed to assess the antiviral activity and tolerability of
      saquinavir. Patients were randomised to receive 25, 75, 200, or 600 mg of
      saquinavir three times daily for 16 weeks. No serious adverse events occurred.
      CD4 cell counts showed a trend indicative of a dose response in favour of the 600
      mg dosage, the maximum increase being seen around week 4. In none of the 8
      patients with positive plasma viraemia at baseline did cultures become negative
      after treatment; peripheral blood mononuclear cell and plasma-viral load by
      culture and DNA and RNA PCR all showed a trend towards reduction at higher doses
      of saquinovir. Saquinavir was well tolerated in this group of previously
      untreated patients with few or no symptoms; this study shows that an HIV
      proteinase inhibitor is active in HIV-infected patients.

PMID- 7715295
TI  - Effect of grapefruit juice on blood cyclosporin concentration.
AB  - Grapefruit juice increases blood concentrations of some dihydropyridine calcium
      channel blockers, which are metabolised by the P450 enzymes that also metabolise
      cyclosporin. We evaluated, in a randomised cross-over study, the effect of
      grapefruit juice on blood cyclosporin concentrations in 14 healthy adults. Each
      subject was given oral cyclosporin 300 mg with 250 mL grapefruit juice, orange
      juice, or water. Area-under-the-curve (AUC) was significantly higher with
      grapefruit juice than with water or orange juice (means 7057, 4871, and 4932 ng
      h/mL, respectively; p < 0.0001). Thus grapefruit juice may provide a non-toxic
      and inexpensive alternative to drugs that are used to reduce cyclosporin dose.

PMID- 7715296
TI  - Is Alzheimer's disease an apolipoprotein E amyloidosis?
AB  - The presence of the apolipoprotein E4 allele has been identified as a major risk
      factor for late-onset Alzheimer's disease. Apolipoprotein E has also been found
      immunohistochemically in Alzheimer's disease lesions. We biochemically isolated
      amyloid beta from senile plaques and found that a carboxyl-terminal fragment
      (residues 216-299) of apolipoprotein E co-purified. In vitro this fragment from
      recombinant apolipoprotein E could form amyloid-like fibrils, which were Congo
      red positive. Thus senile plaques may contain both amyloid beta and
      apolipoprotein E amyloid fibrils.

PMID- 7715298
TI  - Indian kala-azar caused by Leishmania tropica.
AB  - Kala-azar, or visceral leishmaniasis, in India is generally assumed to be a
      result of infection with Leishmania donovani. 15 parasite isolates collected over
      the past 10 years from patients with classical disease were typed by monoclonal
      antibodies, isoenzymes, and kDNA analysis. 4 were shown to be L tropica, a
      species historically associated with cutaneous disease and more recently a mild
      "visceralising" disease from the Desert Storm experience. The results confirm
      that L tropica is a co-endemic agent of visceral leishmaniasis in India, and may
      shed light on the rising frequency of therapeutic unresponsiveness to sodium
      antimony gluconate, which complicates treatment of this lethal disease.

PMID- 7715297
TI  - Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's
      syndrome.
AB  - Gilbert's and Crigler-Najjar syndromes are characterised by unconjugated
      hyperbilirubinaemia due to complete and partial absence of bilirubin UDP
      glucuronosyltransferase (UGT). Nucleotide sequences of the genes for bilirubin
      UGT were analysed in six patients with Gilbert's syndrome. All patients had a
      missense mutation caused by a single nucleotide substitution and the mutations
      were heterozygous. In addition, relatives of patients with Crigler-Najjar
      syndrome types I and II, and of those with Gilbert's syndrome were analysed. All
      ten relatives with mild hyperbilirubinaemia were heterozygotes with respect to
      each defective allele. These results suggest that Gilbert's syndrome is inherited
      as a dominant trait.

PMID- 7715299
TI  - Isotope-selective non-dispersive infrared spectrometry for detection of
      Helicobacter pylori infection with 13C-urea breath test.
AB  - 13C-urea breath tests were sampled in 51 subjects with an isotope-selective non
      dispersive infrared spectrometer (NDIRS) and compared with the results of
      conventional isotope-ratio mass-spectrometry (IRMS). Delta-over-baseline values
      of both methods correlated well (r = 0.976 at 15 min and 0.985 at 30 min, both p
      < 0.0005). With a cut-off for delta-over-baseline values of 5/1000 (i. e., 5 per
      thousand), both methods correctly classified all 36 Helicobacter-pylori-negative
      and all 15 H-pylori-positive subjects. All infected subjects had values over
      11/1000 in all samples with both methods. NDIRS is of equal value as IRMS for the
      diagnosis of H pylori infection. Because NDIRS gives on-line results and is
      easier and cheaper, we consider NDIRS useful for clinical practice.

PMID- 7715300
TI  - Diphtheria immunity in UK blood donors.
AB  - Immunity to diphtheria was determined in serum samples from 1000 UK-born blood
      donors at the North London Blood Transfusion Centre during a three-month period
      in 1993; 125 women and 125 men were stratified in 10-year age groups, from 20 to
      59. A tissue (vero cell)-culture toxin-neutralisation assay was used to measure
      serum diphtheria antitoxin concentrations. According to internationally accepted
      definitions (antitoxin < 0.01 IU/mL = susceptibility, 0.01-0.09 IU/mL = basic
      protection, and > or = 0.1 IU/mL = full protection), 37.6% of donors were
      susceptible to diphtheria, 31.5% had basic protection, and 30.9% were fully
      protected. Log-linear modelling of the influence of age and sex on population
      immunity showed a significant trend (p < 0.001) of decreasing immunity with
      increasing age: 25.2% of donors aged 20-29 were susceptible compared with 52.8%
      of those aged 50-59. There was a small sex effect (p = 0.052); similar
      proportions of men and women were susceptible, but fewer women had full
      protection. There was no age-sex interaction on immunity (p = 0.454). Our results
      suggest that booster immunisation of adults is necessary to increase herd
      immunity of the adult population.

PMID- 7715301
TI  - Standardised patients: as we evaluate, so shall we reap.

PMID- 7715302
TI  - A series of capital hospital cuts.

PMID- 7715303
TI  - HTLV screening of Swedish blood donors.

PMID- 7715304
TI  - Sarin poisoning in Tokyo subway.

PMID- 7715305
TI  - Sarin poisoning in Tokyo subway.

PMID- 7715306
TI  - Hanshin-Awaji earthquake and acute myocardial infarction.

PMID- 7715307
TI  - Primary percutaneous insertion of gastrostomy button.

PMID- 7715308
TI  - Coronary risk factors in people from the Indian subcontinent.

PMID- 7715309
TI  - Coronary risk factors in people from the Indian subcontinent.

PMID- 7715310
TI  - Bubonic plague outbreak in Mozambique, 1994.

PMID- 7715311
TI  - End of New Zealand asthma epidemic.

PMID- 7715312
TI  - End of New Zealand asthma epidemic.

PMID- 7715313
TI  - PCR-based DNA test to confirm clinical diagnosis of autosomal recessive spinal
      muscular atrophy.

PMID- 7715314
TI  - Morbidity or mortality as endpoint for clinical trials in intensive care.

PMID- 7715315
TI  - Early morphological evidence of autosomal recessive polycystic kidney disease.

PMID- 7715316
TI  - Transmission of HIV.

PMID- 7715317
TI  - Long-term health care.

PMID- 7715318
TI  - Ethics of n-of-1 trials.

PMID- 7715319
TI  - Re-inventing WHO.

PMID- 7715320
TI  - Vitamin-D-receptor-gene polymorphism and bone loss.

PMID- 7715321
TI  - Vitamin-D-receptor-gene polymorphism and bone loss.

PMID- 7715322
TI  - Fatal Mycobacterium avium meningitis after mis-identification of M tuberculosis.

PMID- 7715323
TI  - Hippocampal atrophy and cognitive impairment.

PMID- 7715324
TI  - BCL-2 oncoprotein in neuroblastoma.

PMID- 7715325
TI  - Familial disseminated atypical mycobacterial infection in childhood.

PMID- 7715326
TI  - p53-based blood test for p53PIN3 and risk for sporadic ovarian cancer.

PMID- 7715327
TI  - Insulin resistance and membrane abnormalities.

PMID- 7715328
TI  - Insulin resistance and membrane abnormalities.

PMID- 7715329
TI  - Insulin resistance and membrane abnormalities.

PMID- 7715331
TI  - The unequal, the achievable, and the champion.

PMID- 7715330
TI  - Medical Munchausen syndrome.

PMID- 7715332
TI  - Measles vaccination and inflammatory bowel disease.

PMID- 7715333
TI  - Clozapine: back to the future for schizophrenia research.

PMID- 7715334
TI  - Renal grafts from non-heart-beating donors.

PMID- 7715335
TI  - Protective efficacy of hepatitis B vaccination.

PMID- 7715336
TI  - Caffeine dependence.

PMID- 7715337
TI  - Outcome of transplantation of non-heart-beating donor kidneys.
AB  - To reduce the shortage of kidneys for transplantation, we started a non-heart
      beating (NHB) donor programme, and compared the short-term and long-term outcomes
      of kidneys from NHB donors with those of a matched group of kidneys from heart
      beating (HB) donors. 57 NHB kidneys were procured at the University Hospital in
      Maastricht and at three regional hospitals in the Netherlands, and were
      transplanted in 21 transplant centres within the Eurotransplant exchange
      organisation. 114 matched controls from HB donors were selected from
      Eurotransplant files. Mean follow-up was 85 months. At 5 years, graft survival
      was 54% for NHB kidneys and 55% for HB kidneys; patient survival was 75% and 77%.
      Kidneys from NHB donors had a significantly higher rate of delayed graft function
      (60% vs 35%), resulting in a longer hospital stay. Primary non-function of the
      graft was seen as frequently in the NHB donor-kidney group as in the HB group
      (14% vs 8%, p = 0.3). We conclude that NHB donors are a valuable source of
      kidneys for transplantation.

PMID- 7715338
TI  - Is measles vaccination a risk factor for inflammatory bowel disease?
AB  - Measles virus may persist in intestinal tissue, particularly that affected by
      Crohn's disease, and early exposure to measles may be a risk factor for the
      development of Crohn's disease. Crohn's disease and ulcerative colitis occur in
      the same families and may share a common aetiology. In view of the rising
      incidence of inflammatory bowel disease (Crohn's disease and ulcerative colitis),
      we examined the impact of measles vaccination upon these conditions. Prevalences
      of Crohn's disease, ulcerative colitis, coeliac disease, and peptic ulceration
      were determined in 3545 people who had received live measles vaccine in 1964 as
      part of a measles vaccine trial. A longitudinal birth cohort of 11,407 subjects
      was one unvaccinated comparison cohort, and 2541 partners of those vaccinated was
      another. Compared with the birth cohort, the relative risk of developing Crohn's
      disease in the vaccinated group was 3.01 (95% CI 1.45-6.23) and of developing
      ulcerative colitis was 2.53 (1.15-5.58). There was no significant difference
      between these two groups in coeliac disease prevalence. Increased prevalence of
      inflammatory bowel disease, but not coeliac disease or peptic ulceration, was
      found in the vaccinated cohort compared with their partners. These findings
      suggest that measles virus may play a part in the development not only of Crohn's
      disease but also of ulcerative colitis.

PMID- 7715339
TI  - Is lung cancer associated with asbestos exposure when there are no small
      opacities on the chest radiograph?
AB  - This study was designed to test the hypothesis that the risk of lung cancer from
      asbestos exposure is confined to persons with radiographic evidence of pulmonary
      fibrosis. Occupational and smoking histories were obtained from 271 patients with
      a confirmed diagnosis of primary lung cancer and 678 referents (279 with other
      respiratory disease and 399 with cardiac disease). Histories were reviewed blind
      to assess the timing, duration, and probability of exposure to asbestos. To allow
      for a lag between asbestos exposure and the development of lung cancer, subjects
      were classified by the time they had spent in an occupation entailing definite or
      probable exposure more than 15 years before diagnosis. The presence and extent of
      fibrosis was assessed blindly from chest radiographs by three readers and scored
      for small opacities with the ILO 1989 International Classification of Radiographs
      of the Pneumoconioses. 93 (34.3%) cases had worked in an occupation with definite
      or probable asbestos exposure compared with 176 (25.8%) referents (crude odds
      ratio for lung cancer 1.49, 95% CI 1.09-2.04). After adjustment for age, sex,
      smoking history, and area of referral, the odds ratio (95% CI) was 2.03 (1.00
      4.13) in the subgroup of 211 with a median ILO score for small parenchymal
      opacities of 1/0 or more, and 1.56 (1.02-2.39) in the 738 with a score of 0/1 or
      less (ie, those without radiological evidence of pulmonary fibrosis). These
      results suggest that asbestos is associated with lung cancer even in the absence
      of radiologically apparent pulmonary fibrosis.

PMID- 7715341
TI  - Serological evidence of past hepatitis B infection in liver donor and hepatitis B
      infection in liver allograft.
AB  - The presence of hepatitis B surface and core antibodies (anti-HBs and anti-HBc)
      in a liver donor without hepatitis B surface antigen is taken to indicate
      resolution of hepatitis B and is not considered to contraindicate donation. We
      report a liver transplant recipient who developed hepatitis B after such a
      donation. It seems that hepatitis B virus can reside in the liver of a patient
      who has seemingly recovered from his disease. We recommend avoidance of liver
      transplants from donors who are positive for anti-HBs and anti-HBc.

PMID- 7715340
TI  - HIV-1 subtypes and male-to-female transmission in Thailand.
AB  - We examined the risk factors for heterosexual transmission of HIV in a case
      control study of couples in Thailand. 90 HIV-positive men and their regular sex
      partners were enrolled at the immune clinic, Chulalongkorn Hospital, where 92% of
      male index cases had HIV-1 serotype A (subtype E). Most index cases had acquired
      HIV through sexual intercourse. 95 couples were enrolled at 15 detoxification
      clinics, where 79% of them had HIV-1 serotype B (subtype B). Most men had
      acquired HIV through injecting drug use (IDU).

PMID- 7715342
TI  - Sleep apnoea and nocturnal angina.
AB  - Hypoxaemia occurs with sleep apnoea and might induce nocturnal angina. Sleep
      apnoea was found in 9 of 10 patients with nocturnal angina pectoris. Nocturnal
      angina diminished during treatment of sleep apnoea by continuous positive airway
      pressure, and the number of nocturnal myocardial ischaemic events measured by
      computerised vector-cardiography was reduced.

PMID- 7715344
TI  - External examiners.

PMID- 7715343
TI  - Long-term efficacy of continuing hepatitis B vaccination in infancy in two
      Gambian villages.
AB  - In 1984, all non-immune children under the age of 5 years in the Gambian villages
      of Keneba and Manduar were vaccinated against hepatitis B virus (HBV). All
      children born in these villages since 1984 have been vaccinated in infancy.
      Despite a rapid fall in antibody concentrations, vaccine efficacy against HBV
      infection and chronic carriage of HBsAg has increased with time. Overall, vaccine
      efficacies in 1993 against HBV infection and chronic HBsAg carriage were 94.7%
      (95% Cl 93.0-96.0) and 95.3% (91.0-97.5), respectively. Breakthrough infections
      in vaccinated children largely originate from chronic HBsAg carriers. Thus, we
      tested 261 chronic carriers for HBV DNA and e antigen. The prevalence of these
      markers of infectivity, and the amount of HBV DNA, decreased greatly with age.
      Detailed studies of breakthrough infections over two 4-year periods revealed that
      in the second period there were fewer than half the expected numbers of
      infections. Our findings suggest that in Keneba and Manduar long-term vaccination
      is progressively decreasing HBV transmission by chronic carriers, since their
      infectivity diminishes with time.

PMID- 7715345
TI  - Helicobacter pylori: human pathogen or simply an opportunist?

PMID- 7715347
TI  - Progress for patients amid Japan's uncertainty.

PMID- 7715346
TI  - A law that would care for the carers.

PMID- 7715348
TI  - Routine testing of HIV status of babies?

PMID- 7715349
TI  - Adipose tissue trans fatty acids and coronary heart disease.

PMID- 7715350
TI  - Adipose tissue trans fatty acids and coronary heart disease.

PMID- 7715351
TI  - Adipose tissue trans fatty acids and coronary heart disease.

PMID- 7715353
TI  - Pain and hyperalgesia in acute inflammatory and chronic neuropathic conditions.

PMID- 7715352
TI  - Adipose tissue trans fatty acids and coronary heart disease.

PMID- 7715354
TI  - Delayed third hepatitis B vaccine dose and immune response.

PMID- 7715355
TI  - Is neurally mediated hypotension an unrecognised cause of chronic fatigue?

PMID- 7715356
TI  - Is neurally mediated hypotension an unrecognised cause of chronic fatigue?

PMID- 7715357
TI  - Is neurally mediated hypotension an unrecognised cause of chronic fatigue?

PMID- 7715358
TI  - Psychiatric manifestations in girl with ornithine transcarbamylase deficiency.

PMID- 7715359
TI  - Mortality and malnutrition among displaced Liberians in Ivory Coast.

PMID- 7715360
TI  - False positives and negatives in routine testing for drugs of abuse.

PMID- 7715361
TI  - Treatment of children with HIV infection. PENTA (Paediatric European Network for
      Treatment of AIDS)

PMID- 7715362
TI  - Restriction of fat in the diet of infants.

PMID- 7715363
TI  - Water intoxication after nebulised tribavirin.

PMID- 7715364
TI  - Restriction of fat in the diet of infants.

PMID- 7715365
TI  - Restriction of fat in the diet of infants.

PMID- 7715366
TI  - Persistent parvovirus B19 infection.

PMID- 7715367
TI  - Is co-trimoxazole safe?

PMID- 7715368
TI  - Use of mid-upper-arm circumference for nutritional screening of refugees.

PMID- 7715369
TI  - Use of mid-upper-arm circumference for nutritional screening of refugees.

PMID- 7715370
TI  - Lack of association between mitochondrial tRNA(Leu(UUR)) point mutation and
      cluster headache.

PMID- 7715372
TI  - Intraoperative colonoscopy during laparoscopic bowel resection.

PMID- 7715371
TI  - No improvement of refractory sideroblastic anaemia with ubidecarenone.

PMID- 7715373
TI  - Does peroperative gut-mucosa hypoperfusion cause postoperative nausea and
      vomiting?

PMID- 7715374
TI  - Rapid progressive subacute sclerosing panencephalitis after perinatally acquired
      measles virus infection.

PMID- 7715375
TI  - Distortion product emission features and the prediction of pure tone thresholds.
AB  - Distortion product emission (DPE) growth functions, demographic data, and pure
      tone thresholds (PTTs) were recorded in 229 normal-hearing and hearing-impaired
      ears. Half of the data set (115 ears) was used by a discriminant analysis routine
      to classify DPE and demographic features into either a normal PTT group or an
      impaired PTT group (PTT greater than 30 dB SPL [sound pressure level]) at six
      frequencies in the audiometric range. The six discriminant functions developed
      from this classification process were then used to predict PTT group membership
      in the remaining 114-ear data set. Frequency-specific prediction accuracy was
      approximately 85% overall. Of the 45 DPE and demographic variables evaluated, the
      DPE amplitude associated with an f2 (a primary tone of frequency) of moderate
      level (50 dB SPL) and a frequency corresponding to PTT was generally most
      predictive. DPE features associated with frequencies immediately adjacent to the
      PTT frequency also appear to be useful. DPE level was found to be weakly
      correlated with subject age; perhaps for this reason, age was frequently included
      in discriminant functions. This study describes the DPE measures that can most
      reliably categorize PTTs as normal or impaired in large populations with varied
      cochlear hearing status.

PMID- 7715376
TI  - Management of chronic sinusitis in cystic fibrosis.
AB  - Chronic rhinosinusitis is extremely common in patients with cystic fibrosis. It
      causes numerous problems in these patients and can put them at risk for life
      threatening illness. Potential problems include nasal obstruction, congestion,
      sinus pain and pressure, infection (usually with Pseudomonas organisms), hyposmia
      or anosmia, and the seeding of bacteria into the lower respiratory tract. Cystic
      fibrosis patients with chronically infected sinuses are at increased risk for
      pneumonia following lung transplantation. A prophylactic protocol has been
      developed for the management of chronic sinusitis in patients with cystic
      fibrosis. These patients are fully evaluated at the Nasal Dysfunction Clinic of
      the University of California, San Diego (UCSD), Medical Center. Based on the
      results of the evaluation, they are treated with endoscopic sinus surgery,
      partial middle turbinectomy, septoplasty, and a large middle meatal maxillary
      antrostomy. Surgery is followed by a rigorous regimen of pulsatile hypotonic
      saline nasal irrigation to wash away tenacious cystic secretions. Tobramycin
      (Nebcin) is given once daily in the nasal irrigant to inhibit the growth of
      Pseudomonas organisms. At the USCD Nasal Dysfunction Clinic, this prepulmonary
      transplantation protocol is now used in all cystic fibrosis patients with chronic
      sinusitis.

PMID- 7715377
TI  - Cerebrospinal fluid fistula: the identification and management in pediatric
      temporal bone fractures.
AB  - Cerebrospinal fluid (CSF) fistula represents a potentially lethal complication
      and requires a high index of suspicion to make the diagnosis. A 12-year
      retrospective study of pediatric basilar skull fractures identified 147 patients
      with temporal bone fractures, of which 37 patients exhibited evidence of CSF
      fistula. The diagnosis is made from a combination of clinical, radiographic, and
      chemical evaluation. The evolution of diagnostic techniques are reviewed, and the
      more recent and sensitive tests, such as beta-2 transferrin, are emphasized.
      Treatment of CSF fistula is nonsurgical in most cases. Surgical exploration and
      mastoid obliteration were required in two patients, and the indications for
      surgical treatment are explored. The use of antibiotic prophylaxis is
      controversial and not routinely indicated.

PMID- 7715378
TI  - The use of tissue expanders in the correction of ectropion in an animal model.
AB  - The use of tissue expanders in eyelid reconstruction has seen limited
      application. To determine the efficacy of tissue expanders in the correction of
      cicatricial ectropion, an animal model was developed. Lower-eyelid blepharoplasty
      with overcorrection was performed on 18 New Zealand white rabbits. After 1 month,
      if significant ectropion was present, tissue expanders (1.8-cm3
      Cylindrical/Microdome [CUI Corporation, Carpinteria, Calif.]) were inserted on
      one side, the other eye being the control. These were inflated in the following
      weeks to a total volume of 2 cm3. The tissue expanders were then removed, and the
      animals were followed for 1 month. Although the early results were encouraging,
      the ectropion progressed toward its preoperative severity. It appears that lower
      eyelid ectropion remains a therapeutic problem that is only partially corrected
      with tissue expansion alone.

PMID- 7715379
TI  - The cricothyroid muscle does not influence vocal fold position in laryngeal
      paralysis.
AB  - The status of the cricothyroid muscle, which is innervated by the superior
      laryngeal nerve, is believed to influence the vocal fold position in laryngeal
      paralysis. It is believed that isolated lesions of the recurrent laryngeal nerve
      generally result in the paralyzed vocal fold assuming a paramedian position but
      that with lesions of both the superior and recurrent laryngeal nerves, a more
      lateral (intermediate or cadaveric) vocal fold position can be expected. Twenty
      six consecutive patients with unilateral vocal fold paralysis underwent
      transnasal fiberoptic laryngoscopy (TFL) and laryngeal electromyography (LEMG).
      By TFL, the vocal fold positions were paramedian in 8 patients, intermediate in
      7, and lateral in 11. By LEMG, 13 patients had isolated recurrent laryngeal nerve
      lesions and 13 patients had combined (superior and recurrent laryngeal nerve)
      lesions. There was no correlation between the vocal fold position and the status
      of the cricothyroid muscle, i.e., the status of the cricothyroid muscle by LEMG
      did not predict the vocal fold position nor did the vocal fold position by TFL
      predict the site of lesion. In addition, we investigated the possibility that the
      degree of thyroarytenoid muscle recruitment (tone) might correlate with vocal
      fold position, but no relation was found. We conclude that 1. the cricothyroid
      muscle does not predictably influence the position of the vocal fold in
      unilateral paralysis; 2. thyroarytenoid muscle recruitment (tone) does not appear
      to influence vocal fold position; and 3. still unidentified and unknown factors
      may be responsible for determining vocal fold position in laryngeal paralysis.

PMID- 7715380
TI  - A comparative diagnostic study of head and neck nodal metastases using positron
      emission tomography.
AB  - A prospective study was conducted to compare the accuracy of clinical
      examination, computed tomography (CT), and positron emission tomography (PET) in
      identifying head and neck squamous cell carcinoma metastatic to cervical lymph
      nodes. The findings in the necks of 49 patients evaluated by clinical examination
      and CT were compared to the findings in the same necks by PET, a newly available
      metabolic imaging modality. Pathology specimens were available for 45 of the
      necks. The findings of PET and CT correlated in 84% of cases. In the cases that
      did not correlate, CT proved correct in four of five cases. PET (82%) and CT
      (84%) were comparable and were both better than clinical examination (71%) in
      correctly identifying the presence or absence of metastatic disease.

PMID- 7715381
TI  - Complications of endoscopic sinus surgery in a residency training program.
AB  - Endoscopic sinus surgery has emerged in the last decade as the treatment of
      choice for chronic sinusitis. Reports of complications of the procedure from
      different centers vary depending on the technique used and the experience of the
      surgeon. Between August 1990 and August 1993, 337 patients underwent endoscopic
      sinus surgery at West Virginia University. Most of the cases were performed by
      senior residents under faculty supervision. Minor complications were encountered
      in 15.1% of the cases and major complications in 1.5% of the patients. The most
      common major complication was cerebrospinal fluid leak. All patients with
      cerebrospinal fluid leaks were diagnosed and treated successfully at the time of
      surgery. Middle turbinate adhesions and orbital penetration were the most common
      minor complications. Routine partial middle turbinectomy did not decrease the
      adhesion rate. Endoscopic sinus surgery is a relatively safe procedure, even when
      performed by residents under adequate supervision.

PMID- 7715382
TI  - Nasal mucociliary clearance after radiation therapy.
AB  - Irradiation has been demonstrated to cause decreased mucociliary clearance in
      animal models. We sought to verify this effect clinically by using the saccharin
      transport test to evaluate nasal mucociliary clearance in 9 patients previously
      treated with radiation therapy to the nasal cavity. The patients also completed a
      questionnaire examining the prevalence of nasal symptoms before and after
      radiation therapy. Patients who received radiation therapy had no clearance of
      saccharin from the nasal cavity at a minimum of 20 minutes. The controls had a
      median clearance time of 5 minutes. The patients noted a higher prevalence of
      nasal congestion, drainage, and facial pain after radiation therapy. This study
      demonstrates that radiation therapy to the nasal cavity causes a decrease in
      nasal mucociliary clearance. This alteration should be considered when selecting
      therapy for malignancies in the nasal area.

PMID- 7715383
TI  - Comparison of laser Doppler flowmeter and radioactive microspheres in measuring
      blood flow in pig skin flaps.
AB  - Laser Doppler flowmetry is a noninvasive technique commonly used to monitor skin
      perfusion after free-tissue transfer or replantation in reconstructive surgery.
      Several investigators have expressed concern about the reliability of the
      quantitative value provided by laser Doppler flowmeters (LDF) and the extent to
      which they reflect nutrient blood flow. This experiment was designed to compare
      quantitatively the skin blood flow in the pig measured by LDF and by 15-micron
      radioactive microspheres (RMs). It was observed that the skin blood flow rates
      measured by LDF and RMs in the normal skin and in acute random-pattern and
      arterialized skin flaps were highly correlated (r = 0.93, P < .01). However, the
      skin blood flow rates measured by LDF were consistently higher (P < or = .05)
      than the corresponding flow rates measured by RMs, and this discrepancy increased
      considerably at low skin blood flow rates (< 2 mL/min/100 g). We speculated that
      the LDF most likely measured both nutrient and arteriovenous shunt flow in the
      skin and that this arteriovenous shunt flow at least in part caused the
      discrepancy in skin blood flow rates measured by the LDF and RMs because the 15
      micron RMs are known to measure nutrient blood flow only. The inherent variations
      and errors in LDF technique were also discussed.

PMID- 7715384
TI  - Techniques for outcomes research in chronic sinusitis.
AB  - Accurate assessment of patient outcome after sinus surgery requires the
      collection of valid and reliable data. Symptom-based surveys were administered in
      a prospective manner to 104 patients with chronic sinusitis. Test-retest
      reliability for the Chronic Sinusitis Survey based on duration of symptoms (0.86,
      P < .0001) was superior to that for a similar survey based on severity of
      symptoms (0.57, P < .0001). Results of the Chronic Sinusitis Survey also
      correlated significantly with subscales of a general health assessment in the
      extent to which chronic sinusitis limits physical activity (0.40, P < .01),
      interferes with work or other activities (0.36, P < .01), and affects patient
      perception of bodily pain (0.46, P < .001). The Chronic Sinusitis Survey is an
      efficient and reliable method to follow health status and health-related quality
      of life outcomes in patients with chronic sinusitis.

PMID- 7715385
TI  - Radiotherapy in the treatment of verrucous carcinoma of the head and neck.
AB  - Because of reports of anaplastic transformation following irradiation, this study
      examines the incidence of anaplastic transformation and local control of these
      lesions. This review of seven patients who had verrucous carcinoma of the head
      and neck that was treated with irradiation shows local control in 71% of cases.
      There were no cases of anaplastic transformation. This report adds to the
      literature two cases of "de-differentiation" to less differentiated squamous
      carcinomas; one such case occurred after surgery alone. The literature is
      reviewed. Overall, anaplastic transformation is reported in 7% of patients who
      had irradiation. De-differentiation occurs after surgery as well. The rate of
      local control with irradiation is less than 50%; with surgery it is 85%. It is
      concluded that surgery should be used if the procedure has acceptable morbidity.
      Otherwise, irradiation can be used. Failures can be salvaged surgically.
      "Anaplastic transformation" should not affect treatment approach.

PMID- 7715386
TI  - Squamous cell carcinoma of the pyriform sinus: a nonrandomized comparison of
      therapeutic modalities and long-term results.
AB  - From January 1964 through December 1991, 408 patients with squamous cell
      carcinomas involving the pyriform sinus were treated at Washington University
      Medical Center. Their ages ranged from 29 to 83 years (mean, 62.3; median 59) and
      the male to female ratio was 5:1. The mean duration of symptoms prior to
      diagnosis was 3.9 months (range 1 to 32 months) and 89% had a smoking or ethanol
      history. Sixty-seven percent had T3 or T4 lesions and 87% were stage III or IV at
      presentation. Sixty-nine percent had neck metastases. The treatment strategy
      varied with respect to radiation and reconstruction. Prior to 1978, preoperative
      radiation (3.5 to 5000 cGy) was used. Postoperative radiation was given
      thereafter (600+ Gy). Since 1982, flap reconstruction (usually pectoralis major
      myocutaneous) has been used to close the partial laryngopharyngectomy (PLP)
      defect. Almost all N0 necks were treated by radiation or surgery and all N1-N3
      lesions were treated by combined therapy. Pyriform tumors were subdivided into
      three groups: 1. one-wall lesions (n = 48), 2. medial-wall lesions which involved
      the aryepiglottic fold or supraglottis (N = 267), and 3. two- or three-wall
      lesions which extended to the pyriform apex or post-cricoid region (N = 93).
      Ninety-five patients had single-modality therapy and 302 had combined treatment.
      Two hundred seven patients had conservation surgery (PLP) and 157 had total
      laryngopharyngectomy alone or in combination with radiation. Thirty-three
      patients were treated by radiation alone. Eleven patients were excluded from the
      study because of distant metastases (TxNxM1) at presentation. The cumulative
      survival (NED) at 5, 10, 15, and 20 years was 56%, 35%, 31%, and 20%,
      respectively. The cumulative locoregional control rate was 71%. At 5 years (NED),
      the cure rates for one-wall lesions (73%) were better than for medial-wall
      lesions (63%) or 2- and 3-wall lesions (49%). One-wall lesions were smaller,
      medial-wall lesions behaved similar to supraglottic tumors, and two- or three
      wall tumors behaved as hypopharyngeal tumors. The cure rates were related to T
      stage with T1 + T2 > T3 + T4 (28%). Neck metastases reduced the cure rate by 26%
      and N1 > N2-N3 by an additional 12%. Other factors contributing to therapeutic
      failure were distant metastases (17.7%), second primary tumors (6.2%; oropharynx
      and lung were most common), and intercurrent disease fatalities (9.5%). The
      secondary therapeutic salvage rate was 44% for surgery and 32% for radiation
      therapy. The therapeutic complication rate was 19% with 3.6% leading to
      fatality.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7715387
TI  - Eosinophilic infiltration in advanced laryngeal squamous cell carcinoma. Veterans
      Administration Laryngeal Cooperative Study Group.
AB  - Tumor-associated tissue eosinophilia (TATE) has been related to prognosis in
      epithelial cancers, including cancers at several head and neck sites. This study
      prospectively examined 248 patients with stage III and IV laryngeal squamous cell
      carcinoma to determine prevalence and potential prognostic significance of TATE.
      Pretreatment tumor specimens were histopathologically evaluated. Presence and
      degree of TATE were analyzed with regard to other tumor characteristics, patient
      characteristics, and outcome criteria. Median follow-up was 48 months.
      Eosinophilia was found in 22.5% of specimens and was not related to tumor site,
      stage, patient age or sex, or treatment modality. Overall and disease-free
      survival rates and response to induction chemotherapy did not differ
      significantly with respect to TATE. This study represents the first long-term,
      prospective evaluation of TATE and its prognostic significance in a single head
      and neck site. Contrary to the findings of earlier preliminary reports, our
      results suggest that TATE is not a clinical useful prognostic parameter in
      advanced laryngeal squamous cell carcinoma.

PMID- 7715388
TI  - Comparison of surgeries for removal of primary vestibular inputs: a combined
      anatomical and behavioral study in rats.
AB  - Unilateral removal of Scarpa's ganglion and neurectomy of the peripheral
      vestibular nerve branches were compared in rats as methods to eliminate primary
      vestibular input. Ocular nystagmus was consistently observed after both types of
      lesion, but it completely disappeared within 4 to 7 days. Imbalance and rotation
      were more serious and prolonged after ganglionectomy than after peripheral
      neurectomy. Corresponding with these differences in symptoms were differences in
      terminal degeneration. After ganglionectomy, degenerated axons and terminals were
      distributed throughout all terminal regions of primary vestibular fibers on the
      lesioned side, while after peripheral neurectomy, the degeneration was more
      limited. The results of this study suggest that vestibular ganglionectomy is a
      more successful approach than peripheral vestibular neurectomy for removing the
      primary vestibular input.

PMID- 7715389
TI  - Perceptual and respiratory responses to added nasal airway resistance loads in
      older adults.
AB  - The purpose of the present study was to assess breathing behavior under various
      nasal resistance load conditions and, in particular, to determine whether
      respiratory responses to added nasal resistance loads occur before the threshold
      perception of an added load. The participants were 40 older adults who ranged in
      age from 59 to 82 years. Nasal airflow and resistance were measured with the
      pressure-flow technique, which was modified to create calibrated resistance
      loads. Statistical analyses revealed a significant decrease in airflow rate and
      volume during load conditions both before perceptual detection and at detection
      of increased resistance in comparison to a "no load" condition. No differences in
      respiratory behaviors were found between the load condition just before
      perceptual detection of an increased resistance load and the load condition at
      detection. The present findings suggest that physiologic responses to changes in
      the airway environment apparently occur even before there is perceptual
      recognition that the environment has changed.

PMID- 7715390
TI  - Reduction rhinoplasty and nasal patency: change in the cross-sectional area of
      the nose evaluated by acoustic rhinometry.
AB  - The feeling of nasal patency is related to the dimensions of the nasal cavity.
      After aesthetic reduction rhinoplasty, the cross-sectional areas of the nose may
      decrease critically. In this study, acoustic rhinometry, a new method based on
      acoustic reflections, was used to evaluate the internal dimensions of the nasal
      cavity in 37 patients before reduction rhinoplasty and again 6 months after
      surgery. The internal dimensions of the nasal cavity--especially the anterior
      dimensions--were reduced after rhinoplasty. Compared with the preoperative
      values, the minimum cross-sectional area (at the nasal valve) decreased by 22%
      (totally) to 25% (unilaterally) (P = .000), and the cross-sectional areas at the
      piriform aperture decreased by 11% to 13% (P = .02).

PMID- 7715391
TI  - Dehiscence of the jugular bulb in Crouzon's disease.
AB  - Patients with Crouzon's disease have a distorted nasopharynx, which frequently
      leads to retained middle ear secretions and necessitates myringotomy. A review of
      the computed tomographic (CT) scans of 21 ears in 11 patients with Crouzon's
      disease found that 12 jugular bulbs were protruding or dehiscent. The
      relationship between the jugular bulb and the middle ear space was normal
      bilaterally in only 2 of the 11 patients. Consequently, patients with Crouzon's
      disease are at risk for inadvertent puncture of the jugular bulb during
      myringotomy. CT scans obtained prior to myringotomy can be helpful in detecting
      dehiscent or protruding jugular bulbs.

PMID- 7715392
TI  - Prevention of intraoperative contamination from large ulcerative cutaneous
      lesions.
AB  - A method for managing head and neck malignancies with cutaneous ulceration prior
      to excision is described. At our institution all lesions with cutaneous extension
      and erosion have been treated in this manner prior to excision. The exact number
      of treated cases, however, is unknown, since this number is not placed in the
      medical record. Although the risk of tumor "take" resulting from the spillage or
      implantation of tumor cells from an ulcerated lesion is probably small, the
      previously described technique is simple and inexpensive and should be employed
      as a precautionary measure to further minimize this risk.

PMID- 7715393
TI  - Endoscopic intranasal frontal sinusotomy.

PMID- 7715395
TI  - Elective percutaneous (Rapitrac) tracheotomy.

PMID- 7715394
TI  - Iatrogenic facial nerve injury.

PMID- 7715396
TI  - Directory of otolaryngological societies.

PMID- 7715397
TI  - Lymphoma of the head and neck and acquired immunodeficiency syndrome: clinical
      investigation and immunohistological study.
AB  - The epidemic of acquired immunodeficiency syndrome (AIDS) has made an enormous
      impact in the practice of medicine within the past decade. Of the many associated
      problems, the increasing frequency of human immunodeficiency virus (HIV)-related
      malignancies, particularly lymphoma, has been both a fascinating area of study
      and a most difficult clinical condition to manage. This study investigates
      lymphoma of the head and neck with clinical studies, as well as
      immunohistochemical assessments from individual patients. Lymphomas of the head
      and neck, as they present to the otolaryngologist, can present difficult and
      challenging diagnostic and therapeutic dilemmas. It is well-known that a
      significant number of acquired immunodeficiency patients present initially with
      symptoms related to the otolaryngology field; it was also found that a certain
      number of lymphomas in the head and neck in HIV+ patients are the initial
      presentation. In addition, the associated disorders, such as related infections
      and synchronous additional neoplasms, are described. Also presented are
      recommendations for diagnosis and work-up of these conditions, based on the
      experience. In addition, the study of lymphoma as a neoplasm from the molecular
      biology viewpoint and its course in the immunodeficient state have been important
      areas of study in an effort to dissect the progression to oncogenesis. The
      rapidly expanding literature base in this area is discussed.

PMID- 7715398
TI  - Clinical uses of lasers in dermatology.
AB  - The accessibility of the skin to examination and study has permitted
      dermatologists to play an extremely important role in defining the clinical
      usefulness and limitations of many laser systems as well as developing innovative
      concepts, techniques and devices that further improved the effectiveness of laser
      treatment. As new laser technology evolved over the years, dermatologists have
      also helped define the specificity of laser-tissue interaction and employed the
      newly developed laser technologies in innovative ways which further expanded the
      usefulness of these devices. One of the most important concepts to be developed
      by dermatologists--selective photothermolysis--has led to the creation of a
      series of laser systems which have provided numerous unique advantages in the
      management of many common vascular and pigmented conditions of the skin and
      mucous membranes, even in infants and children. The net result of these
      technologic advances has been the creation of new and effective treatment
      techniques which have been so profoundly superior to existing technology that
      they have been rapidly incorporated into the daily practice of most
      dermatologists.

PMID- 7715399
TI  - Laser patch welding: experimental study for application to endoscopic closure of
      bronchopleural fistula, a preliminary report.
AB  - BACKGROUND AND OBJECTIVE: Postoperative bronchopleural fistula is a serious
      complication following pulmonary resection. To close the bronchopleural fistula,
      we developed a new method of endoscopic patch welding using laser tissue welding
      between bronchial tissue and a patch. STUDY DESIGN/MATERIALS AND METHODS: The
      feasibility of the laser patch welding was examined by in vitro and in vivo
      animal experiments. A newly developed carbon monoxide (CO) laser and an Argon ion
      laser were evaluated. Various tissue membranes and artificial membranes were
      evaluated as patch materials. RESULTS: We found that the combination of expanded
      polytetrafluoroethylene (e-PTFE; 200 microns in thickness) and the CO laser with
      contact irradiation method offered the strongest laser patch welding. Using this
      combination, the irradiation at 400 W/cm2 for 10 seconds resulted in 16-18 g of
      measured traction strength at the welding spot (2 mm in diameter). The welded e
      PTFE patch at bronchial stump remained for 5 weeks. CONCLUSION: Our results
      encourage use of this novel laser patch technique for clinical applications.

PMID- 7715400
TI  - Comparison of laser vascular welding, interrupted sutures, and continuous sutures
      in growing vascular anastomoses.
AB  - BACKGROUND AND OBJECTIVES: The argon laser-assisted vascular anastomosis may
      solve the problems of conventional sutured anastomosis, such as vascular stenosis
      and arrest of growth owing to a foreign-body reaction to suture material. STUDY
      DESIGN/MATERIALS AND METHODS: Twelve argon laser-assisted vascular anastomoses,
      seven conventional anastomoses with interrupted sutures, and five conventional
      anastomoses with continuous sutures were performed in 12 young mongrel dogs.
      RESULTS: Five months later, the external diameter at the anastomosis had
      increased 70.5% in the laser group, 67.0% in the interrupted suture group, and
      22.9% in the continuous suture group. Histological examination of the laser
      assisted anastomoses showed almost complete healing, with no granulomatous
      response around the anastomotic site. In the interrupted suture group, marked
      scaring and foreign body reactions were observed on the vessel wall at the site
      of the anastomosis. The continuous suture group showed more remarkable
      disorientation of the vascular layer and intimal hyperplasia than the interrupted
      suture group. CONCLUSION: Vascular anastomosis using the argon laser offers
      advantages over the conventional procedure in growing vessels.

PMID- 7715401
TI  - In vivo cancer diagnosis of the esophagus using differential normalized
      fluorescence (DNF) indices.
AB  - BACKGROUND AND OBJECTIVE: We report the use of new diagnostic parameters based on
      the differential normalized fluorescence (DNF) signals for malignant tumor
      diagnosis. STUDY DESIGN/MATERIALS AND METHODS: Over 200 measurements of
      endogenous fluorescence from normal and malignant esophageal tissues were
      performed during routine endoscopy in 48 patients. A pulsed nitrogen-pumped dye
      laser was used to provide in situ excitation at 410 nm. Direct collection of the
      fluorescence signal emitted by the tissue was achieved using an intensified
      photodiode array detector equipped with a fiberoptic probe. RESULTS: The
      fluorescence signals were normalized with respect to the total fluorescence
      signal area. The cancer diagnosis indices were defined by the difference between
      the normalized fluorescence signal of a tumor and the mean value of a reference
      set of normal tissues. The results of the DNF approach were compared with
      endoscopic examinations and histopathology interpretations of the biopsy samples.
      Excellent correlation in the classification of normal and malignant tumors for
      the samples was found. CONCLUSION: The data indicated that the DNF approach has a
      significant potential to provide a direct, real-time, and in-situ technique for
      cancer diagnosis of the esophagus without requiring biopsy of the tumors and time
      consuming histopathology tests.

PMID- 7715402
TI  - Natural fluorescence of normal and neoplastic human colon: a comprehensive "ex
      vivo" study.
AB  - BACKGROUND AND OBJECTIVE: A microspectrofluorometric analysis on "ex vivo"
      samples from normal tissue and adenocarcinoma of the human colon has been
      performed to characterize the histological, biochemical, and biophysical bases of
      the autofluorescence. STUDY DESIGN/MATERIALS AND METHODS: Differences between
      normal and tumor tissues are found that concern both the intensity distribution
      and spectral shape of the autofluorescence emission. The different pattern of the
      fluorescence intensity can be related to the histological organization of the
      tissue, and involves mainly the arrangement of the submucosa, the most
      fluorescent layer. RESULTS: The most evident differences in the spectral shape
      found in the 480-580 nm range involve the stromal compartment, seem to be due to
      the presence of different fluorochromes, and are possibly related to the host
      response to the tumor. CONCLUSION: The nature and the extent of the
      autofluorescence modification between normal and tumor tissue in sections explain
      at least partly the evidence of the "in vivo" analysis and highlight the
      importance of excitation for full exploitation of the potentials of
      autofluorescence in diagnosis.

PMID- 7715403
TI  - Pulsed Ho:YAG laser meniscectomy: effect of pulsewidth on tissue penetration rate
      and lateral thermal damage.
AB  - BACKGROUND AND OBJECTIVE: Studies need to define the optimal parameters under
      which the holmium laser should operate for arthroscopic meniscectomy. This study
      was designed to analyze the effect of various Holmium wavelength pulsewidths on
      human meniscal tissue penetration rates and lateral thermal injury. STUDY
      DESIGN/MATERIALS AND METHODS: Using a pulsed Holmium: YAG laser at a wavelength
      of 2.1 microns, the effect of various pulse-widths on tissue penetration rates as
      well as the degree of accompanying thermal damage in human meniscal tissue was
      evaluated in a specially designed jig. Holding the energy constant at 500 mJ per
      pulse, the pulsewidth was varied between 100 and 600 microseconds. RESULTS: Fiber
      penetration of meniscal tissue was found to be fastest at a pulsewidth of 250
      microseconds. As the pulsewidth was increased or decreased around this number,
      the observed penetration time decreased, although no statistical difference was
      found. The size of the hole created was inversely related to the penetration
      time. Microscopic examination revealed zones of lateral thermal effect extending
      800 microns from the ablation site. CONCLUSION: No relationship between the
      pulsewidth and the lateral thermal effect could be found.

PMID- 7715404
TI  - Plastic hollow waveguides: properties and possibilities as a flexible radiation
      delivery system for CO2-laser radiation.
AB  - BACKGROUND AND OBJECTIVES: One significant inconvenience of the CO2 laser is the
      lack of flexible fibers essential for endoscopic applications. The goal of this
      study is to test the feasibility of hollow waveguides in view of a practical use
      in medicine. STUDY DESIGN/MATERIALS AND METHODS: Various types of plastic hollow
      waveguides for flexible delivery of CO2 laser radiation were examined. The
      transmission losses, divergence angle, damage threshold, and input and output
      beam profiles were determined. The interaction process between radiation
      transmitted through these guides with soft as well as hard tissues was studied.
      RESULTS: Plastic hollow waveguides can transmit high power (up to 50 W) with low
      losses (straight guide 1 dB/m) even through bendings. The divergence angle is <
      13 degrees. Cutting quality and extent of thermal damage are comparable to
      incisions performed with a free laser beam. CONCLUSION: The results of this study
      show good cutting quality and durability of these flexible plastic hollow
      waveguides, which render possible to deliver CO2 radiation in the power range
      needed for most surgical applications with affordable transmission losses.
      Plastic hollow waveguides are, therefore, a real alternative to replace the
      mirror arms.

PMID- 7715405
TI  - Characteristics of Nd:YAG sculptured contact probes after prolonged laser
      application.
AB  - This study analyzed the functional and structural characteristics of cone,
      hemisphere, and modified sculptured contact fibers (1,000 microns) after 1 hour
      of continuous Nd:YAG laser application. Continuous laser application was
      performed on live porcine tissue using 20 watts of power. The fiber's appearance
      under a microscope as well as the power output was recorded after 0, 5, 10, 20,
      30, 45, and 60 minutes of continuous laser application. (N = 3 for each fiber).
      At time 0, all fibers transmitted from 49 to 56% of the initial 20 watts (W);
      power transmission decreased to less than 9% relative power transmission after 20
      minutes and then plateaued. The fibers exhibited severe distortion and
      carbonization of the surface where laser had been applied with evidence of quartz
      melting and shattering after only 10 minutes. By 30 minutes of laser application,
      all three fibers were fractured and essentially indistinguishable from one
      another; moreover, the fibers exhibited similar power transmission, and cutting
      and coagulation activity, as determined by a panel of independent, double-blinded
      surgeons. These data lead us to conclude that 1) Nd:YAG contact laser effects
      result from thermal heating of the fiber tip with subsequent tissue injury, 2)
      the unique structural configuration of the fiber's sculptured tip are lost after
      several minutes of laser application without appreciable change in functional
      integrity, and 3) fibers may be manually fractured allowing for multiple uses
      without significant sacrifice of power transmission or surgical utility.

PMID- 7715406
TI  - Is there a need for guidelines for OB/GYN residents to use the laser?
AB  - BACKGROUND AND OBJECTIVE: With the developing technologies and the extensive use
      of different wavelength lasers for treatment of some gynecologic conditions, many
      residencies in the United States face pressure to give credentialing to residents
      wishing to utilize the laser(s). The objective of this study was to assess the
      need for credentialing. STUDY DESIGN/MATERIALS AND METHODS: A survey was sent to
      all U.S. program directors of obstetrics and gynecology. RESULTS: Of 281 surveys
      mailed, 138 responded (49.1%); 136 utilized some wavelength laser in the
      treatment of some gynecologic conditions. The most commonly used laser was the
      carbon dioxide (CO2), and the least used was the argon laser. Eighty-four
      programs (61.8%) had a written policy; 54 (38.2%) did not. Postgraduate courses
      were necessary in 81 programs (59.6%), leading to some form of credentialing.
      CONCLUSIONS: The vast majority of programs (98.6%) utilized some wavelength laser
      as a therapeutic modality in gynecology, and 73.5% of the residency programs
      would like standardized guidelines for residents.

PMID- 7715407
TI  - [Follow-up study of changes in respiratory function in the same workers after an
      additional 6 years of exposure to pollutants in the rubber industry].
AB  - Follow-up study of respiratory function was carried out in a group of 311 male
      workers employed in one rubber industry. The prevalence of respiratory symptoms
      and ventilatory capacity were recorded over te period of six years. Lung function
      was measured by recording maximum expiratory flow-volume (MEFV) curves on which
      forced vital capacity (FVC), one-second forced expiratory volume (FEVI) and flow
      rates at 50% and the last 25% of the vital capacity (FEF50, FEF25) were read. The
      prevalence of all chronic respiratory symptoms was higher during the follow-up
      study although not statistically significant (p > 0.05). During both studies
      smokers had significantly higher prevalence of chronic cough, chronic phlegm and
      chronic bronchitis than nonsmokers (p < 0.05 or < 0.025). Measured values of
      ventilatory capacity were significantly lower than predicted normal values during
      both studies (p < 0.01). Percentage of predicted values were lower during the
      follow-up study in comparison to that during the initial study. The mean lowest
      percentages were obtained for FEF25 (initial study: 77.4%; follow-up study:
      70.5%). Smokers had larger mean annual decrease of FVC: 0.073 L; FEVI: 0.063 L;
      FEF50: 0.100 L/s; FEF25: 0.085 L/s than nonsmokers (FVC: 0.063 L; FEVI: 0.058 L;
      FEF50: 0.083 L/s; FEF25: 0.058 L/s). Workers exposed for more than 10 years had
      larger mean annual decrease of ventilatory capacity tests than hose with shorter
      exposure. Our data indicate that exposure to noxious agents in rubber industry
      may be responsible for the development of chronic respiratory symptoms and
      chronic lung function changes.

PMID- 7715408
TI  - [Headache in displaced persons from east Slavonia].
AB  - The authors investigate the appearance of psychogenic headaches among 150
      displaced persons of both sexes, average age 43 years with specific prepared
      questionnaire (Incidental Report Interview with questions important for the
      culture of examinees), neurological and psychiatric checkups. Diagnosis of
      headache was established according to the criteria of the Headache Classification
      Committee of the International Headache Society. In the group of 150 displaced
      persons the authors have found 106 (70%), 31 (30%) among males and 75 (70%) among
      females) psychogenic headaches. Psychogenic headache appeared in 53% of the male
      cases and was connected with psychoticism (1.7%), conversion (8.3%) and
      depression (43%), and in 81% of the female cases expression of conversion (4.3%)
      or a follower of anxiety (10.7%) and depression (66%). Headache is together with
      anxiety and depression most frequently found in the age groups 31-40 and 51-60
      years, among married individuals (76%), and among those with secondary school
      education (86%). In the group of psychogenic headaches, 13 (42%) males and 23
      (30%) females had elements of muscle contraction (tension) headaches, and 9 (29%)
      males and 8 (10%) females, mainly from the groups 31-40 and 51-60 years with
      lower educational level had elements of combined vascular and tension headaches.
      There was a positive correlation between the employment before exile,
      unemployment in exile, the loss of experience in changing the place of living,
      leaving home and country under pressure and in peril of death and appearance and
      intensity of psychogenic headaches.

PMID- 7715409
TI  - [Fatal rupture of an echinococcal cyst into the right atrium].
AB  - The case of a man 32 years of age with echinococcosis of the heart who died due
      to rupture of a pericardial echinococcal cyst into the right atrium with the
      range into the pulmonary circulation and fatal embolism of the branch of
      pulmonary artery is presented. Such localization of echinococcus is extremely
      unusual as well as the complication it caused, and promoted this report which is
      very instructive for a clinician, the more so that the patient was surgically
      treated, but irregularly followed up, and the disease had a poor outcome.
      Prophylaxis with albendazole over a period of one month and more frequent control
      examinations by means of adequate diagnostic methods in such cases is stressed.

PMID- 7715410
TI  - [A fetal bone as a foreign body in the uterus].
AB  - The ultrasound examination of a 49-year-old female patient with irregular and
      painful menstruations has revealed a foreign body in the uterus. In 1973 (19
      years prior to procedure), the patient had an artificial abortion and since then
      has not been able to conceive. In 1977, hysterosalpingography and laparoscopy did
      not reveal the cause of infertility. Hysteroscopy was undertaken and diaphysis of
      a fetal bone 22 mm long was removed. This bone was most probably, functioning as
      an intrauterine device, the cause of infertility. Thus, the authors' findings
      strengthen once again the association between abortion and infertility. It is
      concluded that transvaginal sonography and hysteroscopy open new possibilities in
      identifying and treating such disturbances.

PMID- 7715411
TI  - [Brainstem auditory evoked potentials in healthy and at risk neonates].
AB  - Brainstem auditory evoked potentials were done in 10 healthy full-term newborns
      and 10 high risk newborns. Absolute latencies of waves I, III and V as well as
      interwave intervals I-V were measured. In relation to the values in healthy
      newborns the prolonged latencies of waves I, III and V were found in the group of
      high risk newborns. The prolonged latency of wave shows the decreased velocity of
      conduction, as a result of normal axonal transport.

PMID- 7715412
TI  - [Lung auscultation: an old skill with new interpretation and terminology].
AB  - The lung sound auscultation is a part of everyday practice of most physicians.
      This skill used to be in practice in antique times, but it did not gain any
      particular attention until the beginning of the 19th century when Laennec
      systematized his observations, so that the method became generally accepted as
      the means of examining the patient. Today the stethoscope has almost become the
      symbol of medical profession, and without it no worthy caricature on behalf of a
      physician is possible. In this article except short historical review of the lung
      auscultation, the new technical innovations, including the use of computers which
      have led to new insights into the characteristics of the lung sounds in health
      and disease have been shown. Indeed, the technical innovations have insured more
      accurate measurement of all characteristics of lung sounds, and in connection
      with this enabled the coining of new terms, especially for adventitious lung
      sounds. As the whole civilized world has agreed upon the terminology, in the
      radiance of the above mentioned we are also proposing new terminology for
      adventitious lung sounds.

PMID- 7715413
TI  - [50 years of molecular biology].
AB  - In 1865, Johann Gregor Mendel laid the mathematical foundation of the science of
      genetics. His "elements of heredity" (later called genes) were postulated as pure
      algebraic units. At about the same time (1868), Friedrich Miescher extracted a
      gelationous substance from the nuclei of white blood cells found in pus. This
      substance was called nuclein; later it became known as nucleic acid. Fifty years
      ago, Oswald T. Avery and his colleagues showed that one type of nucleic acid--DNA
      mediates genetic transformation in pneumococci. This was the first demonstration
      that Miescher's nuclein is the repository of Mendel's hypothetical elements of
      heredity. The genes thus "materialized". Although not recognized by
      contemporaries, Avery's discovery may be considered as a landmark in the history
      of biology. The molecular era of genetics and biology has begun. Other events
      associated with the beginning of this new era (bacteriophage research, work on
      nutritional mutants in Neurospora) are also described in the present review.

PMID- 7715414
TI  - [Response of the official Varazdin city physician, Dr. Bernard Vilim Muller, to
      the city magistrates concerning the delivery of a child by a Varazdin physician,
      Dr. Josip Mlinaric].
AB  - A Croatian translation of a Latin document dated February 15, 1836 found in the
      Historic Archives of the city of Varazdin is presented. The document concerns two
      Varazdin physicians from the first half of the nineteenth century. One of them,
      the official city physician, replies to the questions of the Municipal Board
      about the act committed by the other physician during delivery of a child. Rough
      curricula vitae of both physicians are also given. The physician's reply is a
      very strong criticism and condemnation not only of the other physician's act, but
      also of this work, lack of professional attitude, and dubious personal qualities.
      A negative judgement is also passed on the city surgeon of the time. The author
      offers possible ground for such criticism, and states his opinion about incorrect
      relationship between colleagues as physicians and men, that is matter not only of
      the past.

PMID- 7715415
TI  - [Proposed criteria for becoming established as a clinical facility].

PMID- 7715416
TI  - Illness and response among south Indian foragers.
AB  - The medical system of Paliyan foragers of south India is described on the basis
      of ethnographic field study. Observational and interview data on etiological
      theories, shamanistic diagnostic practices, and measures for prevention and
      treatment of illness and injury are examined in relation to one another. Paliyans
      give considerable importance to naturalistic as well as personalistic etiologies.
      They regard diagnosis of efficient causes as a matter of practicality; case
      studies illustrate how such causes are diagnosed. Aspects of the system are
      examined in global and regional comparative perspective.

PMID- 7715418
TI  - Tryptophan deficiency and alcohol consumption in rats as a model for
      disadvantaged human populations: a preliminary study.
AB  - Choice of diet is a combination of socioeconomic, psychological, and biological
      factors. This article reports on a preliminary study using an animal model and
      approximating the dietary conditions found on some Native American reservations.
      The results suggest that alcohol consumption in these disadvantaged populations
      may be a result of tryptophan deficiency. Tryptophan-deficient rats consumed more
      alcohol under ad-libitum conditions, perhaps to compensate for the lack of this
      essential amino acid. Tryptophan is the biological precursor of serotonin, a
      central neurotransmitter that has been implicated in mood elevations and
      declines. Alcohol has been found to mimic the effects of tryptophan or serotonin.
      We suggest that alcohol consumption may act to compensate for the dietary
      deficiency of this amino acid. The model attributing alcohol consumption to
      tryptophan deficiency thus connects socioeconomic, psychological, and biological
      factors.

PMID- 7715417
TI  - A cross-cultural comparison of adaptation to chronic pain among Anglo-Americans
      and native Puerto Ricans.
AB  - Using quantitative and qualitative data from studies in New England and Puerto
      Rico, we compare the chronic pain experiences of Anglo-Americans and native
      Puerto Ricans. We also compare adaptation to chronic pain between and within
      these two groups. Positive adaptation is defined as the process of adjustment in
      behavior and attitudes which facilitates resumption and continuation of a life
      defined by the subject as meaningful and worthwhile. Our case studies and
      quantitative analyses demonstrate that successful adaptation is associated with a
      reduction in depression, tension, and worry; and the realistic continuation of
      family, social, and work roles. Our analyses also demonstrate that the factors
      most often associated with adaptation are cultural (meanings and standards),
      psychosocial (social support, age, socioeconomic status, psychological coping
      style), the cultural context of care (providers' world views), and the political
      and economic circumstances under which compensation and rehabilitation are
      sought. Our quantitative analyses show significant inter- and intra-cultural
      group differences in pain intensity and emotional responses to the pain. However,
      despite higher pain intensity and more emotional responses among Puerto Ricans,
      there was no significant difference between the two groups regarding interference
      in daily activities. The two groups simply appear to experience chronic pain
      differently. We propose that the difference is not positive or negative in itself
      -it is simply a different reality which should be evaluated from an emic
      perspective and not through the cultural lens of the outside provider or
      researcher. Intra-group analyses are essential because they provide insight into
      the standards, norms, and variations within specific cultural groups.

PMID- 7715419
TI  - Lay conceptions of autism: parents' explanatory models.
AB  - This article reports the results of a study of lay conceptions of autism. The
      subjects were 33 parents of autistic children. The study utilized Kleinman's
      explanatory model perspective and examined parents' beliefs about autism with
      respect to the nature and onset of symptoms, the etiology of the affliction and
      the illness outcomes for their children. The parents' explanatory models varied
      in significant ways from the biomedical perspective on autism. The results also
      identified gender based differences regarding parental beliefs about the etiology
      of the illness.

PMID- 7715420
TI  - Apoptosis induced by bacterial pathogens.
AB  - Programmed cell death is part of normal development and homeostasis. Apoptosis
      induced by bacteria appears to contribute to infectious diseases. Some bacteria
      produce toxins to kill host cells by the same pathway, apoptosis, through
      different mechanisms including pore formation, protein synthesis inhibition or
      adenylate cyclase activity. Other bacterial pathogens' mechanisms to induce
      apoptosis, for example, that of S. flexneri, remain to be elucidated. How the
      bacterial toxins or the bacteria interact with eukaryotic cell-death-related
      genes and then possibly trigger a cell-death program would make an interesting
      study. The understanding of the mechanism of apoptosis induced by bacteria could
      be important in the development of therapy and prevention of infectious diseases.

PMID- 7715421
TI  - Insertional inactivation of the gene for the meningococcal lactoferrin binding
      protein.
AB  - The lactoferrin binding protein (LBP) of Neisseria meningitidis (the putative
      meningococcal receptor for human lactoferrin, LF), has been previously
      characterized as an outer-membrane protein of approximately 105 kDa. Using N
      terminal amino acid sequence to generate an oligonucleotide probe, a clone from a
      lambda gt11 phage library was isolated. This clone was subjected to shuttle
      mutagenesis, in which an erythromycin mini-transposon was used to interrupt the
      LBP coding sequence. This insertion mutation was introduced into the
      meningococcus. A N. meningitidis strain that carried this transposon insertion no
      longer produced the 105 kDa protein. The absence of this protein was correlated
      with the inability to bind LF or to use LF as an iron source. The LBP mutant was
      able to grow with other Fe sources and demonstrated no other visible membrane
      protein alterations. These data confirm the suggestion that LBP is the
      meningococcal receptor.

PMID- 7715422
TI  - The effect of growth temperature on Staphylococcus aureus binding to type I
      collagen.
AB  - Many strains of Staphylococcus aureus produce a collagen-binding surface protein
      that could enable these strains to colonize tissues such as bone. Previous
      studies indicated that the expression of the collagen receptor varies with growth
      conditions. We report here that the growth temperature influences the ability of
      some S. aureus strains to produce this receptor. S. aureus isolates from human,
      osteomyelitic bone were grown at 37 degrees C and 42 degrees C and tested for
      agglutination of collagen-coated latex beads. Binding by 42 degrees C grown cells
      was significantly reduced in five of the seven isolates studied, including a
      complete loss of collagen binding in three of these isolates. In an 125I-collagen
      binding assay, the binding ability of one of these isolates, strain #16, was 20
      fold lower if grown at 42 degrees C. Reduced collagen binding by this isolate
      could be demonstrated after only two cell divisions at 42 degrees C and the cells
      regained the ability to bind collagen when shifted back to 37 degrees C. Sodium
      dodecyl sulfate (SDS)-PAGE confirmed the presence of proteins at 117 kDa in
      strain #16 and 135 kDa in SMH which were absent following growth at 42 degrees C.
      Chicken IgG, specific for the 117 kDa protein, was found to react in immunoblot
      assays with these proteins as well as a protein of 135 kDa extracted from S.
      aureus Cowan 1. The antibody did not react with proteins extracted from non
      binding strains. Strains #15 and #21, collagen-binders at both 37 degrees C and
      42 degrees C, produced immunoreactive proteins at 110 and 135 kDa, respectively,
      in lysates from cells grown at both temperatures. Antibody against a recombinant
      form of a previously characterized collagen receptor was used to confirm cross
      reactivity with these novel collagen receptors. These data suggest that the
      ability to produce the collagen receptor is temperature sensitive in some S.
      aureus strains associated with osteomyelitis. It is proposed that a better
      understanding of the environmental effects on collagen receptor production could
      enhance our understanding of staphylococcal infections in bone and joints.

PMID- 7715423
TI  - Binding of type-I collagen to Chlamydia trachomatis.
AB  - Denatured type-I collagen was found to bind to Chlamydia trachomatis elementary
      bodies (EBs) in a time-dependent and specific manner. Specificity was tested by
      having a large excess of other proteins present in the binding mixture. Only
      denatured type-I collagen efficiently competed for binding. Radiolabelled
      fibronectin did not bind under the test conditions used. The binding was
      temperature-dependent and the interaction increased at the melting temperature of
      the collagen. Evidence was found for two binding sites: one with high affinity
      (Kd 3.3 x 10(-9)) and one with low affinity (Kd 1.7 x 10(-7)), with an estimated
      number of binding sites per EB of 590 and 2900, respectively. The interaction
      between C. trachomatis and collagen may also be relevant in vivo, since 50%
      binding occurred at 37 degrees C. The binding to denatured collagen may be of
      importance for the development of sexually acquired reactive arthritis.

PMID- 7715424
TI  - Introduction of plasmid carrying an incomplete set of genes for aerobactin
      production alters virulence of Escherichia coli HB101.
AB  - The aerobactin-mediated iron uptake system is encoded by pColV-K30 and other ColV
      plasmids. It has been known to contribute to the ability of Escherichia coli to
      cause pyelonephritis and cystitis. In the present study an attempt was made to
      evaluate the contribution of an incomplete set of genes for aerobactin synthesis
      to the virulence of Escherichia coli HB101. Escherichia coli HB101 was
      transformed with a recombinant plasmid pJHCV-12 (Tetr and Kanr) carrying
      aerobactin genes (complete first two genes, iucA and iucB and part of the third
      gene iucC) from pColV-K30. Both HB101 and a transformant H10 grew equally well
      when applied to a Vero cell line. These strains were tested for their ability to
      invade and kill Vero cells in monolayers. Light micrographs showed cell damage by
      the transformant carrying pJHCV-12 plasmid and this cytotoxic effect correlated
      with the amount of lactate dehydrogenase (LDH) released. In contrast, strain
      HB101 and HB101 containing parent vector pVK102 did not produce any cytotoxic
      effects. When the ability of these strains to produce ascending pyelonephritis in
      a mouse model was compared, the transformant established itself better in renal
      tissue than the control strain HB101, when assessed 2h, 4 h and 5 days post
      infection.

PMID- 7715425
TI  - Nucleotide sequence of the Salmonella typhi groEL heat shock gene.
AB  - Heat shock proteins (HSP) have been shown to elicit a strong immune response
      during infection by a variety of pathogens. The HSP60 gene of Salmonella typhi
      was amplified using oligonucleotide primers based on the Escherichia coli groEL
      sequence. The nucleotide sequence of the amplified fragment was determined and
      used to predict the amino acid sequence of S. typhi GroEL. The E. coli and S.
      typhi proteins were found to be highly similar; however, several non-conservative
      substitutions near the carboxy-termini of the two polypeptides were found.
      Knowing the amino acid sequence of the S. typhi HSP60 homologue will enhance our
      knowledge of host immune recognition of HSP produced by bacterial pathogens.

PMID- 7715426
TI  - [Histopathological and functional study of the kidney in non-insulin dependent
      diabetes mellitus].
AB  - The histopathological characteristics of the kidney using light microscopy and
      immunofluorescence studies in samples obtained by renal percutaneous biopsy in 19
      women and 7 men with non-insulin dependent diabetes mellitus (NIDDM) (mean of
      age: 55.07 +/- 9.04 yr and mean of "known" diabetes duration: 7.50 +/- 6.87 yr)
      were studied. The relationship with age, blood pressure, diabetic retinopathy and
      other complementary diagnostic methods such as serum creatinine (Cr), creatinine
      clearance (CrC), renal plasma flow (RPF), proteinuria and filtration fraction
      (FF) were also determined. Light microscopy studies detected 92.3% of patients
      with renal lesions of different degrees of severity. The presence and severity of
      glomerulopathy and arteriolopathy were related to diabetes duration (r: 0.764)
      and they were related to each other (rs: 0.773). In 2 patients, lesions were not
      observed and in 11 out of 14 patients with less than 5 yr of diabetes duration,
      mild lesions were detected. However, the histological changes became worse after
      that period. The glomerulopathy was also statistically correlated with Cr, CrC,
      RPF, proteinuria and FF. By immunofluorescence, fibrinogen, IgA and C3 were the
      most frequent and intense precipitates observed. They increased with diabetes
      duration and were located predominantly in the wall and the periphery of the
      glomerules and in renal tubules, suggesting that they originated by trapping.
      There were no precipitates in the mesenchyma, they were scarce in the interstice,
      Bowman's capsule and arterioles. Statistical correlation between diabetic
      histopathological renal changes and retinopathy was found. These results confirm
      that lesions in the kidney and retina in non-insulin dependent diabetic patients
      generally appear and evolve in a similar manner. Hypertension was diagnosed in
      80.76% of patients, without statistical correlation between blood pressure and
      renal lesions. This suggests that at the onset, in non-insulin dependent diabetic
      patients hypertension and nephro-pathy are caused by different and independent
      pathogenic mechanisms. However, at an end stage, it seems that both situations
      can influence each other in a way that their evolution becomes more severe.
      Nephropathy in non-insulin dependent diabetes mellitus displayed scarce clinical
      signs and poor laboratory evidence except when the renal lesions become too
      severe. The lack of correlation between renal lesions and patients' age and blood
      pressure suggests the participation of diabetes at the onset of kidney structural
      impairment.

PMID- 7715427
TI  - [Closed hepatic injuries. Role of computerized axial tomography in the non
      surgical therapy].
AB  - We studied 33 patients with acute abdominal trauma, hepatic lesions and
      intraperitoneal hemorrhage. No surgical attitude was adopted, analyzing the CT
      appearance of the intraparenchymal lesions as well as the associated
      hemoperitoneum. One of the patients who had suffered left hepatic laceration did
      not have a good evolution. The most frequent lesions were intraparenchymal
      hematoma, lobar lacerations and subcapsular hematoma. In two cases, drainage of
      the intrahepatic collections were needed. The presence of hemoperitoneum was not
      an indication for emergency surgery. These results confirm the present tendency
      of conservative management with clinical, CT and ultrasound control of the
      different hepatic injuries, when the patients are hemodynamically stable.

PMID- 7715428
TI  - [Comparison of intestinal parasite infestation indexes among HIV positive and
      negative populations].
AB  - This study was carried out on two groups of patients treated at the Jose de San
      Martin Clinical Hospital. One group was composed of 82 HIV-seropositive patients
      with no signs of diarrhea, and another one of 300 patients, not suspected of HIV
      infection, was considered as "control population". Stool samples were collected
      from each patient and examined for intestinal parasites. These determinations
      were carried out at the Department of Clinical Biochemistry, in the same
      Hospital. Three specimens were obtained from each patient and processed in an
      identical form. Concentration methods, a direct smear technique after
      centrifugation and the trichrome staining procedure were performed on each
      sample. The HIV-positive group was found to harbor a higher proportion of
      intestinal parasites. Outstanding differences between both groups in percentages
      of parasitoses were observed. Species found in a significantly higher percentage
      among HIV seropositive patients were: Entamoeba histolytica (26.5%), Iodamoeba
      butschlii (16.9%), Dientamoeba fragilis (25.3%), Blastocystis hominis (51.8%),
      Cryptosporidium sp. (7.2%), and probably Isospora belli (1.2%). No significant
      differences in percentages of Giardia lamblia, Entamoeba coli, Chilomastix
      mesnili and helminths were observed between both groups. Within the HIV-positive
      group, a higher proportion of infestation due to E. histolytica and I. butschlii
      was observed in homosexuals-bisexuals than in intravenous drug addicts or
      heterosexuals.

PMID- 7715429
TI  - [Response to bronchodilators among patients with bronchial asthma].
AB  - The response to bronchodilators was evaluated in 295 spirometric studies
      performed in 82 patients with asthma (defined according to ATS criteria, with at
      least one previous basal test with 20% of change in FEV1 compared with the
      present test). The response to bronchodilators (Bd) was measured fifteen minutes
      after the inhalation of salbutamol 200 mcg by metered dose inhaler and in the
      absence of Bd inhalation in the previous six hours. Sixty-eight spirometries
      (23%) were classified as with no response to Bd (NR) (absolute delta FEVI[delta
      abs] < 200 ml, delta FEV1 in percentage of initial FEVI[delta%] < 15%, delta FVC
      in percentage of the initial [delta FVC] < 15% and delta FEF 25-75% in percentage
      of the initial [delta FEF] < 25%). Only 23% (n = 16) of them showed an initial
      FEVI greater than 80% of predicted. In this group 4 tests (5% of NR, 1.3% of the
      whole) showed delta abs > 150 ml and 1 (1.5% of NR, 0.3% of whole) delta% > 12%.
      Thirty six percent of the whole population (n = 109) would have been classified
      as NR taking as unique criterion delta VEF1% < 15%, 24 of which (8% of whole
      population) showed delta VEF1 abs > 200 ml (initial FEVI 2.48 +/- 0.60 l) (Table
      3). On the other hand, 94 spirometries (31% of the whole) would have been
      classified as NR taking as unique criterion delta abs < 200 ml. twelve of which
      (4% of the whole) showed delta% > 15% (initial FEVI 0.81 +/- 0.171) (Table
      2).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715431
TI  - Neural spread of Junin virus in intraperitoneally inoculated rats.
AB  - On the basis of an already demonstrated Junin virus (JV) neural route after
      peripheral footpad infection of newborn rats, here we attempted to determine the
      viral pathway following intraperitoneal inoculation. As from the 2nd week post
      infection, neurological disease developed reaching 84% mortality at 30 days.
      Immunoperoxidase labeling of viral antigen, concomitantly with infectivity assays
      and histological examination, was carried out in serially harvested samples.
      Whenever infectivity was detected, whether by viral rescue from coculture or by
      conventional isolation, viral antigen staining was achieved. Infective JV was
      present at threshold levels in spleen and liver from days 2 to 10, and in blood
      from days 5 to 15. In neural tissues, viral antigen was initially disclosed at
      day 5 in thoracic rachideal ganglia and related spinal cord segments. From day 7
      thereafter, the entire spinal cord was involved; at this stage, first evidence of
      viral infection was found in brain stem, with subsequent spread to other
      encephalon structures at day 10. According to harvested samples, no significant
      differences were found in labeled cell percentages at thoracic vs cervical or
      lumbar levels of spinal cord. In contrasts, greater involvement of cerebral
      cortex versus brain stem, hippocampus or cerebellum was demonstrated shortly
      before death. Although JV antigen was overwhelmingly predominant in neurons, no
      morphological changes were apparent in such cells. Since rachideal spinal ganglia
      and spinal cord infection invariably preceded viral spread to encephalon,
      concomitantly with viral clearance from lymphoreticular organs and blood, a
      neural pathway seems warranted.

PMID- 7715432
TI  - [Retinopathy associated with acute pancreatitis].
AB  - Purtscher's retinopathy is a retinal lesion associated with different diseases
      such as cardiac aneurism, thoracic compression, bone fractures, post-trauma,
      pancreatitis and eclampsia. It consists in the appearance of white patches and
      retinal hemorrhage encircling an apparently normal optic disk. There is some
      controversy about its pathogenesis, but a probable cause for the development of
      this affection might be leukocyte emboli activated by complement. We present the
      case of a patient who developed a Purtscher's like retinopathy while he was being
      treated for pancreatitis.

PMID- 7715430
TI  - [Inactivation of myocardial dihydrolipoamide dehydrogenase by Cu(II) and hydrogen
      peroxide].
AB  - The inactivation of pig-heart dihydrolipoamide (LipDH) by oxy-radicals generated
      by Cu(II), supplemented or not with hydrogen peroxide (Fenton system-Cu(II): SF
      Cu(II)) or ascorbate (Cu(II)--Asc), was studied. The reagents concentrations used
      were 2.5-10 microM Cu(II): 3.0 mM H2O2, and 0.5 mM ascorbate. After 5 minutes
      incubation at 30 degrees, LipDH activity was measured as described by Gutierrez
      Correa and Stoppani (Reference 13). As a result of peroxide effect, LipDH
      lipoamide reductase activity decreased in most cases by 83-98% (with the SF
      Cu(II) and Cu(II)-Asc system) or 46-53% with Cu(II) only. The enzyme diaphorase
      activity increased several-fold (Table 1), thus showing a site-specific damage of
      LipDH thiols. NAD+, dihydrolipoamide, GSSG, CAPTO-PRIL, metal chelators (L
      histidine, bathocuproine, EDTA, DETAPAC), trypanothione and allopurinol)
      protected LipDH from inactivation by SF-Cu(II) (Tables 2, 4-6). The same
      compounds, GSH, dithiothreitol, N-acetylcysteine, mercaptopropionylglycine and DL
      penicillamine protected the enzyme from inactivation by Cu(II) (Tables 2, 4-6). L
      cysteine only protected from Cu(II), to a limited degree (Table 4). Compounds
      protecting LipDH did not reactivate the inactivated enzyme (Table 7). NADH (Table
      2), OH-DOPAMINE, DOPA, dihydroxy-phenylacetic acid (DOPAC) and catechol (Table 8)
      enhanced LipDH inactivation by the SF-Cu(II) but not by Cu(II), except OH
      dopamine. ATP and ADP enhanced LipDH inactivation by Cu(II), but not by SF-Cu(II)
      (Table 3). HO scavengers (benzoate, mannitol, ethanol) and superoxide dismutase
      did not prevent LipDH inactivation by Cu(II) and H2O2. Catalase protected but its
      action was not related to its catalytic activity (Table 9). LipDH inactivation by
      oxygen radicals and its modification by therapeutic agents are discussed in the
      context of the physiopathology of heart injury after post-ischemic reoxygenation.

PMID- 7715434
TI  - [Thoracic pain and disorientation in a patient anticoagulated because of mitral
      valve prosthesis].

PMID- 7715433
TI  - [Central alveolar hypoventilation with cor pulmonale: successful treatment by non
      invasive intermittent positive pressure ventilation].
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 of provoked
      hypercapnia, prolonged breath-holding time and correction of hypercapnia by
      voluntary ventilation. Progesterone (200 mg/d during 3 weeks) or naloxone did not
      improve either arterial blood gases (ABG) or the P 0.1/PCO2 curve. Hypoxemia and
      hypercapnia were not corrected during metabolic acidosis provoked by
      acetazolamide (250 mg/d). Nasal CPAP did not control hypoventilation periods.
      Mechanical ventilation was initiated with negative pressure (NPV) through a
      poncho. The patient presented severe discomfort with NPV and obstructive apneas
      were verified during it. She refused to continue NPV. Mechanical ventilation was
      initiated with positive intermittent pressure (IPPV) through a nasal mask. The
      patient had excellent tolerance to the procedure. SpO2 during IPPV was always
      higher than 95%. During sleep induction (under IPPV), respiration in phase with
      the ventilator 1: 1 was observed; instead, during consolidated sleep there was a
      complete dependence of the ventilator with apnea for over 2 min when IPPV was
      interrupted (Fig. 1). After 2 months of treatment, a relief of right ventricular
      failure occurred and hematocrit fell to 39%. There was an improvement of day-time
      ABG (Table I). The P. 0.1/PaCO2 curve 3 months after IPPV was the same as the
      previous one (Fig. 2). The patient has been for 18 months on home
      ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715435
TI  - [Alcoholic osteopathy].
AB  - Alcohol intake is one of the multiple risk factors for developing osteoporosis.
      Alcohol has direct toxic effects on osteoblasts which determines lower
      osteocalcin levels at an early stage, and histomorphometric changes later on.
      Some authors found not only diminished bone formation in alcoholics, but also
      increased bone resorption. The effect of alcoholism on calciotropic hormones
      includes fall of PTH serum levels after an acute or moderate alcohol intake,
      causing transient hypoparathyroidism. In chronic alcoholism, serum levels of
      vitamin D and its metabolites are decreased independently of any liver disease,
      probably related to alcohol influence on enzymatic systems. The mineral
      homeostasis of alcoholics is affected: hypocalcemia is found in acute
      intoxication, with hypo or hypermagnesemia. In chronic alcoholism the serum
      calcium values tend to be normal. Alcohol intake causes multiple endocrine
      changes that lead to hypogonadism in both sexes. The stimulation of hypothalamus
      hypophyseal-adrenal axis contributes to the alcoholic bone disease, because of
      the adverse effects of corticoids on bone. Caloric and protein malnutrition, in
      addition to a dissipated life style are additional risk factors for the
      development of osteoporosis.

PMID- 7715436
TI  - [Between Hippocrates and Galen].

PMID- 7715437
TI  - [Perception of the respiratory effort].

PMID- 7715438
TI  - [Free radical-tissue injury. Its importance in the post-ischemia reperfusion].

PMID- 7715439
TI  - [Kikuchi-Fujimoto's histiocytic necrotizing lymphadenitis].

PMID- 7715440
TI  - [Bladder transitional carcinoma. Evaluation of prognostic factors].

PMID- 7715441
TI  - The sss gene product, which affects pyoverdin production in Pseudomonas
      aeruginosa 7NSK2, is a site-specific recombinase.
AB  - Pyoverdin production by Pseudomonas aeruginosa strain 7NSK2 was induced by Zn(II)
      in the presence of iron. A mutant was isolated in which Zn(II) no longer induced
      pyoverdin production. The sss gene which was inactivated in this mutant was
      cloned and sequenced. Its protein sequence showed 50% identity to the XerC
      protein of Escherichia coli, which is a member of the lambda integrase family of
      site-specific recombinases. An open reading frame was found upstream of sss whose
      protein sequence showed strong identity to DapF, the diaminopimelate epimerase.
      In E. coli, xerC is part of a multicistronic unit that also contains dapF. The
      sss gene of P. aeruginosa could restore site-specific recombination at cer in an
      E. coli xerC mutant and the E. coli xerC gene could complement a genomic sss
      mutation in P. aeruginosa.

PMID- 7715442
TI  - Expression of the genes coding for the Escherichia coli integration host factor
      are controlled by growth phase, rpoS, ppGpp and by autoregulation.
AB  - Transcriptional control of the himA and the himD/hip genes coding for the two
      subunits of the integration host factor (IHF) was investigated. The promoters for
      the two genes were identified by the use of primer extension and S1 analysis.
      Expression from both promoters was found to increase as the cells enter
      stationary phase. Mutation in rpoS, known to be induced upon entry to stationary
      phase, dramatically reduced the growth-phase response of the himA P4 promoter but
      had only a small effect on the induction of the himD/hip promoter. The increased
      activity of both promoters required the presence of the relA and spoT genes,
      suggesting that ppGpp plays a major role in the response to stationary phase. An
      artificial increase in ppGpp in exponentially growing cells induced a rapid
      increase in himA P4 and himD/hip mRNA levels. Experiments with a mutant defective
      in rpoS showed that the response of the himA P4 promoter to high ppGpp levels was
      greatly reduced while that of himD/hip was only slightly affected. Therefore, it
      seems that different mechanisms involving RpoS and ppGpp regulate the growth
      phase response of the two promoters. We propose that the effect of ppGpp on himA
      P4 is mediated via RpoS whereas the himD/hip promoter is affected by ppGpp
      independently of RpoS. Expression of the himD/hip and himA genes was found to be
      subject to negative autoregulation. IHF-binding sites, implicated in
      autoregulation, were found to overlap both the himD/hip and himA P4 promoters. An
      additional IHF-binding site was found upstream of the himD/hip promoter. All
      three sites show low binding affinity to IHF suggesting that autoregulation can
      take place only after sufficiently high levels of IHF accumulate in the cell.

PMID- 7715443
TI  - PilR, a transcriptional regulator of piliation in Pseudomonas aeruginosa, binds
      to a cis-acting sequence upstream of the pilin gene promoter.
AB  - The PilR protein of Pseudomonas aeruginosa is a transcriptional activator of the
      pilin gene and belongs to a two-component sensor-regulator family. PilR was
      overproduced by fusing pilR to the gene for the maltose-binding protein (malE),
      yielding a MalE-PilR hybrid protein. The plasmid with the malE-pilR fusion, when
      introduced into a non-piliated pilR mutant strain of P. aeruginosa, restored
      piliation, indicating that the hybrid protein retains PilR function in vivo. The
      MalE-PilR protein was purified from Escherichia coli and used in a series of DNA
      binding studies. A specific pilin promoter-binding activity of MalE-PilR was
      observed in a gel retardation assay. Subsequent DNase I footprinting analysis
      revealed a 40 bp PilR-binding site located at the -120 to -80 region, relative to
      the transcriptional start site of the pilin gene. This PilR-binding region
      consists of a nine-base sequence and three consensus sequences of 5'-(N)4
      6C/GTGTC-3', in a tandem array in which the first 7-9 bp are bound by the PilR on
      the non-coding strand, leaving the last two nucleotides (TC) unbound. On the
      coding strand, PilR binds to sequences complementary to the two middle consensus
      sequences of the non-coding strand. A sequence similar to the NifA recognition
      site (5'-TGT-(N)11-ACA-3') is also found within the PilR-binding region. Deletion
      analysis and disruption of the individual consensus PilR-binding sequences by
      site-directed mutagenesis revealed that all four PilR-binding sites are
      absolutely required for the PilS/PilR-mediated pilin gene expression.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7715444
TI  - Immunobiology of purified recombinant outer membrane porin protein I of Neisseria
      gonorrhoeae.
AB  - Gonococcal porins (Por) from strains FA19 (Por-1, serogroup A), MS11 (Por-2,
      serogroup B) and FA6434 (Por-5, a hybrid porin containing epitopes from both
      serogroups), were expressed in Escherichia coli and purified under non-denaturing
      conditions. Porins were inserted into liposomes, and they were bound by
      monoclonal antibodies which bind native Por and intact gonococci, but not
      denatured Por. All three recombinant porins (rPor) were highly immunogenic in
      rabbits without additional adjuvant. The rPor antisera were specific for Por by
      Western blotting and whole-cell radioimmunoprecipitation and were broadly cross
      reactive within serogroups. Post-immune, but not pre-immune, sera bound to intact
      gonococci, induced deposition of complement components C3 and C9 onto gonococcal
      membranes and increased association with and activation of human neutrophils.
      Gonococci were not killed in bactericidal assays, and there was no phagocytic
      killing with gonococci opsonized with recombinant antisera. Lack of killing in
      bactericidal assays was not caused by the presence of blocking antibodies to the
      outer-membrane protein Rmp.

PMID- 7715445
TI  - The chromosomal DNA of Streptomyces lividans 66 is linear.

PMID- 7715446
TI  - Iron piracy: acquisition of transferrin-bound iron by bacterial pathogens.
AB  - The mechanism of iron utilization from transferrin has been most extensively
      characterized in the pathogenic Neisseria species and Haemophilus species. Two
      transferrin-binding proteins, Tbp1 and Tbp2, have been identified in these
      pathogens and are thought to be components of the transferrin receptor. Tbp1
      appears to be an integral, TonB-dependent outer membrane protein while Tbp2, a
      lipoprotein, may be peripherally associated with the outer membrane. The relative
      contribution of each of these proteins to transferrin binding and utilization is
      discussed and a model of iron uptake from transferrin is presented. Sequence
      comparisons of the genes encoding neisserial transferrin-binding proteins suggest
      that they are probably under positive selection for variation and may have
      resulted from inter-species genetic exchange.

PMID- 7715447
TI  - Specificity domain localization of Bacillus thuringiensis insecticidal toxins is
      highly dependent on the bioassay system.
AB  - The Bacillus thuringiensis crylA(a) and crylA(c) gene specificity regions were
      probed by creating and testing hybrid toxins both in vivo and in vitro against
      cultured insect cells or dissociated midgut epithelial cells. Toxin threshold
      dose determinations revealed that CrylA(c) is highly active against cultured
      Choristoneura fumiferana cells (CF-1) whereas CrylA(a) is nontoxic. In live
      insect bioassays, a reversed order of toxicity was observed. Hybrid analysis
      revealed that the CrylA(c) toxicity-determining region is located between codons
      258 and 510. Two smaller subsections of this region (residues 258-358 and 450
      510) were able to confer toxicity, although at lower levels, and one region (358
      450) was present where progressive substitutions of crylA(a) with crylA(c)
      sequences had no effect. Exchanging the non-homologous N-terminal regions of
      CrylA(c) with CrylE suggested that the N-terminus does not play a role in
      specificity. One hybrid clone, MP80, displays a 99.3% homology to CrylA(b) but
      shows an 800-fold increase in toxicity to CF-1 cells relative to that shown by
      CrylA(b). Direct comparison between live Bombyx mori bioassays and a newly
      developed in vitro lawn assay using dissociated midgut epithelial cells from the
      same insect revealed striking differences in toxicity. The toxicity-determining
      region for B. mori larvae was determined to be between codons 283 and 450,
      although the 450-620 codon region may exert an influence on toxicity. In general,
      native or hybrid toxins showing little or no insect intoxication were very active
      against the epithelial cells, suggesting that factors other than toxin amino acid
      sequence play an important role in determining toxin specificity.

PMID- 7715448
TI  - Successive action of Escherichia coli chaperones in vivo.
AB  - Escherichia coli DnaK, DnaJ and GrpE are required for renaturation of heat
      inactivated lambda Cl857 repressor (Gaitanaris et al., 1990). Here we demonstrate
      that in addition to the above three proteins, GroEL and GroES are necessary for
      the Cl857 repressor to acquire full activity at the permissive temperature.
      Although full-length soluble repressor is present at normal amounts, the protein
      has reduced specific activity and migrates abnormally on native gels. To
      determine where the different chaperones act in protein folding, we identified
      their cellular locations. DnaK and DnaJ are associated with nascent polypeptide
      chains in translating ribosomes. In contrast, GroEL, although it is transiently
      associated with newly synthesized proteins, is absent from the ribosomes. This
      suggests that DnaK and DnaJ play an early role in protein maturation, whereas
      GroEL acts at a later stage.

PMID- 7715449
TI  - Topological and mutational analysis of KpsM, the hydrophobic component of the ABC
      transporter involved in the export of polysialic acid in Escherichia coli K1.
AB  - The 17 kb kps gene cluster of Escherichia coli K1, which encodes the information
      required for synthesis, assembly and translocation of the polysialic acid capsule
      of E. coli K1, is divided into three functional regions. Region 3 contains two
      genes, kpsM and kpsT, essential for the transport of capsule polymer across the
      cytoplasmic membrane. The hydrophobicity profile of KpsM suggests that it is an
      integral membrane protein while KpsT contains a consensus ATP-binding site. KpsM
      and KpsT belong to the ATP-binding cassette (ABC) superfamily of membrane
      transporters. In this study, we investigate the topology of KpsM within the
      cytoplasmic membrane using beta-lactamase fusions and alkaline phosphatase
      sandwich fusions. Our analysis provides evidence for a model of KpsM having six
      membrane-spanning regions, with the N- and C-terminal domains facing the
      cytoplasm, and a short domain within the third periplasmic loop, which we refer
      to as the SV-SVI linker localizing in the membrane. Protease digestion studies
      are consistent with regions of KpsM exposed to the periplasmic space. In vivo
      cross-linking studies provide support for dimerization of KpsM within the
      cytoplasmic membrane. Linker-insertion and site-directed mutagenesis define the N
      terminus, the first cytoplasmic loop, and the SV-SVI linker as regions that are
      important for the function of KpsM in K1 polymer transport.

PMID- 7715450
TI  - Isolation of motile and non-motile insertional mutants of Campylobacter jejuni:
      the role of motility in adherence and invasion of eukaryotic cells.
AB  - A method of insertional mutagenesis for naturally transformable organisms has
      been adapted from Haemophilus influenzae and applied to the study of the
      pathogenesis of Campylobacter jejuni. A series of kanamycin-resistant insertional
      mutants of C. jejuni 81-176 has been generated and screened for loss of ability
      to invade INT407 cells. Eight noninvasive mutants were identified which showed 18
      200-fold reductions in the level of invasion compared with the parent. Three of
      these eight show defects in motility, and five are fully motile. The three
      mutants with motility defects were further characterized to evaluate the method.
      One mutant, K2-32, which is non-adherent and non-invasive, has an insertion of
      the kanamycin-resistance cassette into the flaA flagellin gene and has greatly
      reduced motility and a truncated flagellar filament typical of flaA mutants. The
      adherent non-invasive mutants K2-37 and K2-55 are phenotypically paralysed, i.e.
      they have a full-length flagellar filament but are non-motile. All three mutants
      show an aberration in flagellar structure at the point at which the filament
      attaches to the cell. Mutants K2-37 and K2-55 represent overlapping deletions
      affecting the same gene, termed pflA (paralysed flagella). This gene encodes a
      predicted protein of 788 amino acid residues and a molecular weight of 90,977
      with no significant homology to known proteins. Site-specific insertional mutants
      into this open reading frame result in the same paralysed flagellar phenotype and
      the same invasion defects as the original mutants. The differences in adherence
      between the two classes of flagellar mutant suggest that flagellin can serve as a
      secondary adhesion, although other adhesins mediate a motility-dependent
      internalization process. Characterization of the mutants at the molecular level
      and in animal models should further contribute to our understanding of the
      pathogenicity of these organisms.

PMID- 7715451
TI  - Amoebapores, a family of membranolytic peptides from cytoplasmic granules of
      Entamoeba histolytica: isolation, primary structure, and pore formation in
      bacterial cytoplasmic membranes.
AB  - Three peptides with pore-forming activity were isolated from the cytoplasmic
      granules of pathogenic Entamoeba histolytica by acidic extraction, gel filtration
      and reversed-phase high-performance liquid chromatography. Partial amino acid
      sequence analysis of the three active peptides revealed that the most abundant of
      them was amoebapore and the other two were isoforms thereof. Cloning and
      sequencing of genomic DNA resolved the amino acid sequence of the two newly
      recognized peptides. The three peptides designated amoebapores A, B and C were
      found to have the same molecular size but to differ markedly in their primary
      structure, although all six cysteine residues are conserved. Despite sequence
      divergence, structural implications predict for the three peptides a similar
      amphipathic alpha-helical conformation stabilized by disulphide bonds. All three
      isoforms exhibit pore-forming activity toward lipid vesicles, but they differ in
      their kinetics. They also are capable of perturbing the integrity of bacterial
      cytoplasmic membranes and thereby kill Gram-positive bacteria. The amoebapores
      represent a distinct family of membrane-active peptides that may function
      intracellularly as antimicrobial agents but may also confer cytolytic activity on
      the parasite.

PMID- 7715452
TI  - Regulation of the Yersinia enterocolitica enterotoxin Yst gene. Influence of
      growth phase, temperature, osmolarity, pH and bacterial host factors.
AB  - The chromosome of Yersinia enterocolitica encodes an enterotoxin called Yst. We
      analysed transcription of chromosomal yst'--luxAB and plasmid-borne yst'--lacZ
      operon fusions and we observed that regulation of yst expression occurs at
      transcriptional level. In a wild-type strain, yst was transcribed from at least
      two major promoters. yst transcription reached a maximum at the entry to the
      stationary phase and significantly varied in different Y. enterocolitica strains.
      In some strains, it gradually decreased during the course of our work, suggesting
      the existence of a mechanism switching the expression of yst to a silent state.
      Changes in the status of bacterial host factors rather than modifications in the
      yst gene are responsible for this silencing. Negative regulator YmoA participates
      in yst silencing and temperature regulation of yst. YmoA was also required for
      proper growth-phase regulation of yst, although it is not the only factor
      involved in this regulation. Physico-chemical parameters of the environment play
      an important role in yst transcription. In usual culture media (e.g. tryptic soy
      broth), the enterotoxin gene was transcribed only at temperatures below 30
      degrees C, which argued against the role of Yst in a prolonged diarrhoea at body
      temperatures. However, yst transcription could be induced at 37 degrees C by
      increasing osmolarity and pH to the values normally present in the ileum lumen.
      This finding reconciles the observations concerning yst expression in a host
      environment and in bacterial cultures, thus supporting the idea that enterotoxin
      Yst is a virulence factor of Y. enterocolitica.

PMID- 7715453
TI  - Cloning and disruption of the gene encoding an extracellular metalloprotease of
      Aspergillus fumigatus.
AB  - Aspergillus fumigatus secretes a serine alkaline protease (ALP) and a
      metalloprotease (MEP) when the fungus is cultivated in the presence of collagen
      as sole nitrogen and carbon source. The gene encoding ALP was isolated and
      characterized previously. We report here the cloning and the sequencing of the
      gene encoding MEP. Genomic and cDNA clones were isolated from A. fumigatus
      libraries using synthetic oligonucleotides as probes. Stretches of the deduced
      amino acid sequence were found to be in agreement with the N-terminal amino acid
      sequence of MEP and with internal peptide sequences. The amino acid sequence of
      the enzyme contains a putative active-site sequence HEYTH homologous to the
      active site of other bacterial and eukaryotic zinc metalloproteases. Sequence
      analysis reveals that MEP has a pre-proregion consisting of 245 amino acid
      residues preceding the 388 amino acid residues of the mature region (molecular
      mass of 42 kDa). An alp mep mutant, deficient in proteolytic activity at neutral
      pH in vitro, was constructed and tested for pathogenicity in a murine model. No
      difference in pathogenicity was observed between the wild-type strain and the alp
      mep double mutant, suggesting that ALP and MEP are not essential for the invasion
      of the lung tissues by A. fumigatus.

PMID- 7715454
TI  - Signal-sensing mechanisms of the putative osmosensor KdpD in Escherichia coli.
AB  - The KdpD protein is a membrane-located sensory kinase (or signal transducer)
      critically involved in the regulation of the kdpABC operon that is responsible
      for a high-affinity transport system in Escherichia coli. In this study, a set of
      KdpD mutants, each resulting in a single amino acid substitution around the
      membrane-spanning regions of KdpD, was isolated. Amino acid substitutions in
      these KdpD mutants were located non-randomly, particularly within the C-terminal
      half of the membrane-spanning regions. This set of KdpD mutants exhibited altered
      transmembrane-signalling properties in response to external K+ and other stimuli.
      In particular, these mutants were found to be insensitive, if not completely, to
      the K+ signal. However, they were able to respond to other stimuli such as high
      salt stress, as in the wild type. Therefore, in contrast to the wild type, the
      cells carrying these mutations exhibited high levels of the steady-state
      expression of kdp, regardless of external K+, provided that high concentrations
      of ionic solutes were supplemented to the cultures. More interestingly, the set
      of KdpD mutants could also respond to high concentrations of external non-ionic
      solutes such as sucrose and D-arabinose, thereby increasing substantially the
      steady-state expression of kdp in response to the medium osmolarity. Furthermore,
      it was found that certain chemicals, ethanol, chlorpromazine and procaine, could
      function as effectors for the KdpD mutants at relatively low concentrations in
      the media. Based on these findings, we have examined the primary signal(s) that
      regulates the function of KdpD. We propose here that KdpD can be considered to be
      an environmental sensor that exhibits sensing mechanisms in response to both the
      level of K+ and the physico-chemical state of the cytoplasmic membrane.

PMID- 7715455
TI  - Characterization of a gene responsible for the Na+/H+ antiporter system of
      alkalophilic Bacillus species strain C-125.
AB  - An alkali-sensitive mutant, 38154, of the alkalophilic Bacillus sp. strain C-125
      could not grow at an alkaline pH. The nucleotide sequence of a 3.7 kb parental
      DNA fragment that recovers the growth of 38154 at alkaline pH has four open
      reading frames (ORF1-4). By subcloning the fragment, we demonstrated that a 0.25
      kb DNA region is responsible for the recovery. Direct sequencing of the mutant's
      corresponding region revealed a G to A substitution. The mutation resulted in an
      amino acid substitution from Gly-393 to Arg of the putative ORF1 product, which
      was deduced to be an 804-amino-acid polypeptide with a molecular weight of
      89,070. The N-terminal part of the putative ORF1 product showed amino acid
      similarity to those of the chain-5 products of eukaryotic NADH quinone
      oxidoreductases. Membrane vesicles prepared from 38154 did not show membrane
      potential (delta psi)-driven Na+/H+ antiporter activity. Antiporter activity was
      resumed by introducing a parental DNA fragment which recovered the mutant's
      alkalophily. These results indicate that the mutation in 38154 affects, either
      directly or indirectly, the electrogenic Na+/H+ antiporter activity. This is the
      first report which shows that a gene responsible for the Na+/H+ antiporter system
      is important in the alkalophily of alkalophilic microorganisms.

PMID- 7715456
TI  - Ribosomal protein methylation in Escherichia coli: the gene prmA, encoding the
      ribosomal protein L11 methyltransferase, is dispensable.
AB  - The prmA gene, located at 72 min on the Escherichia coli chromosome, is the
      genetic determinant of ribosomal protein L11-methyltransferase activity.
      Mutations at this locus, prmA1 and prmA3, result in a severely undermethylated
      form of L11. No effect, other than the lack of methyl groups on L11, has been
      ascribed to these mutations. DNA sequence analysis of the mutant alleles prmA1
      and prmA3 detected point mutations near the C-terminus of the protein and
      plasmids overproducing the wild-type and the two mutant proteins have been
      constructed. The wild-type PrmA protein could be crosslinked to its radiolabelled
      substrate, S-adenosyl-L-methionine (SAM), by u.v. irradiation indicating that it
      is the gene for the methyltransferase rather than a regulatory protein. One of
      the mutant proteins, PrmA3, was also weakly crosslinked to SAM. Both mutant
      enzymes when expressed from the overproducing plasmids were capable of catalysing
      the incorporation of 3H-labelled methyl groups from SAM to L11 in vitro. This
      confirmed the observation that the mutant proteins possess significant residual
      activity which could account for their lack of growth phenotype. However, a
      strain carrying an in vitro-constructed null mutation of the prmA gene,
      transferred to the E. coli chromosome by homologous recombination, was perfectly
      viable.

PMID- 7715457
TI  - Helicobacter pylori hspA-hspB heat-shock gene cluster: nucleotide sequence,
      expression, putative function and immunogenicity.
AB  - All Helicobacter pylori isolates synthesize a 54 kDa immunodominant protein that
      was reported to be associated with the nickel-dependent urease of H. pylori. This
      protein was recently recognized as a homologue of the heat-shock protein of the
      GroEL class. The gene encoding the GroEL-like protein of H. pylori (HspB) was
      cloned (pILL689) and was shown to belong to a bicistronic operon including the
      hspA and hspB genes. In Escherichia coli, the constitutive expression of the hspA
      and hspB genes was initiated from a promoter located within an IS5 insertion
      element that mapped upstream to the two open reading frames (ORFs). IS5 was
      absent from the H. pylori genome, and was thus acquired during the cosmid cloning
      process. hspA and hspB encoded polypeptides of 118 and 545 amino acid residues,
      corresponding to calculated molecular masses of 13.0 and 58.2 kDa, respectively.
      Amino acid sequence comparison studies revealed that, although H. pylori HspA and
      HspB proteins were highly similar to their bacterial homologues, the H. pylori
      HspA featured a striking motif at the C-terminus. This unique motif consists of a
      series of cysteine and histidine residues resembling a nickel-binding domain,
      which is not present in any of the other bacterial GroES homologues so far
      characterized. When the pILL689 recombinant plasmid was introduced together with
      the H. pylori urease gene cluster (pILL763) into an E. coli host strain, an
      increase of urease activity was observed. This suggested a close interaction
      between the HspA and HspB proteins and the urease enzyme, and a possible role for
      HspA in the chelation of nickel ions. The genes encoding each of the HspA and
      HspB polypeptides were cloned, expressed independently as proteins fused to the
      maltose-binding protein (MBP) and purified in large scale. The MBP-HspA and MBP
      HspB fusion proteins were shown to retain their antigenic properties. Both HspA
      and HspB represent antigens that are specifically recognized by the sera from H.
      pylori-infected patients. Whereas HspB was known to be immunogenic in humans,
      this is the first demonstration that HspA per se is also immunogenic.

PMID- 7715458
TI  - The site-specific recombination system regulating expression of the type 1
      fimbrial subunit gene of Escherichia coli is sensitive to changes in DNA
      supercoiling.
AB  - We have studied the effect of altering the in vivo level of DNA supercoiling on
      the phase-variable expression of the Escherichia coli fimA gene. Transcription
      from the fimA promoter was unaffected by changes in DNA supercoiling whether
      caused by the introduction of a topA::Tn10 mutation or by inhibition of DNA
      gyrase with the antibiotic novobiocin. However, inversion of the fimA promoter
      fragment was altered in response to perturbation of DNA supercoiling.
      Specifically, inactivation of topA reduced the rate of promoter fragment
      inversion in both the ON-to-OFF and the OFF-to-ON directions. This effect
      correlated with the loss of functional topA and not with the global level of DNA
      supercoiling. Inhibition of DNA gyrase introduced a bias in favour of the OFF-to
      ON inversion; the ON-to-OFF inversion was affected only slightly. Changes in
      expression of fimB, the gene coding for the recombinase that catalyses fimA
      promoter fragment inversion in the strains used in this study, did not correlate
      with effects on fimA phase variation: we found that transcription of fimB was
      inhibited by loss of functional topA and was enhanced by inhibition of DNA gyrase
      in a manner that correlated well with the global level of in vivo DNA
      supercoiling. A model is presented to account for the effects of lost
      topoisomerase function on fimA gene expression.

PMID- 7715459
TI  - The gene encoding the periplasmic cyclophilin homologue, PPIase A, in Escherichia
      coli, is expressed from four promoters, three of which are activated by the cAMP
      CRP complex and negatively regulated by the CytR repressor.
AB  - The rot gene in Escherichia coli encodes PPIase A, a periplasmic peptidyl-prolyl
      cis-trans isomerase with homology to the cyclophilin family of proteins. Here it
      is demonstrated that rot is expressed in a complex manner from four overlapping
      promoters and that the rot regulatory region is unusually compact, containing a
      close array of sites for DNA-binding proteins. The three most upstream rot
      promoters are activated by the global gene regulatory cAMP-CRP complex and
      negatively regulated by the CytR repressor protein. Activation of these three
      promoters occurs by binding of cAMP-CRP to two sites separated by 53 bp.
      Moreover, one of the cAMP-CRP complexes is involved in the activation of both a
      Class I and a Class II promoter. Repression takes place by the formation of a
      CytR/cAMP-CRP/DNA nucleoprotein complex consisting of the two cAMP-CRP molecules
      and CytR bound in between. The two regulators bind co-operatively to the DNA
      overlapping the three upstream promoters, simultaneously quenching the cAMP-CRP
      activator function. These results expand the CytR regulon to include a gene whose
      product has no known function in ribo- and deoxyribonucleoside catabolism or
      transport.

PMID- 7715460
TI  - Nucleotide sequence, organization and expression of rdgA and rdgB genes that
      regulate pectin lyase production in the plant pathogenic bacterium Erwinia
      carotovora subsp. carotovora in response to DNA-damaging agents.
AB  - In most soft-rotting Erwinia spp., including E. carotovora subsp. carotovora
      strain 71 (Ecc71), production of the plant cell wall degrading enzyme pectin
      lyase (Pnl) is activated by DNA-damaging agents such as mitomycin C (MC).
      Induction of Pnl production in Ecc71 requires a functional recA gene and the rdg
      locus. DNA sequencing and RNA analyses revealed that the rdg locus contains two
      regulatory genes, rdgA and rdgB, in separate transcriptional units. There is high
      homology between RdgA and repressors of lambdoid phages, specially phi 80. RdgB,
      however, has significant homology with transcriptional activators of Mu phage.
      Both RdgA and RdgB are also predicted to possess helix-turn-helix motifs. By
      replacing the rdgB promoter with the IPTG-inducible tac promoter, we have
      determined that rdgB by itself can activate Pnl production in Escherichia coli.
      However, deletion analysis of rdg+ DNA indicated that, when driven by their
      native promoters, functions of both rdgA and rdgB are required for the induction
      of pnlA expression by MC treatment. While rdgB transcription occurs only after MC
      treatment, a substantial level of rdgA mRNA is detected in the absence of MC
      treatment. Moreover, upon induction with MC, a new rdgA mRNA species, initiated
      from a different start site, is produced at a high level. Thus, the two closely
      linked rdgA and rdgB genes, required for the regulation of Pnl production, are
      expressed differently in Ecc71.

PMID- 7715461
TI  - Reproductive health, use of estrogen and experience of symptoms in perimenopausal
      women: a population-based study.
AB  - OBJECTIVE: The aim of the study was to examine reproductive health, use of
      estrogen, lifestyle, experience of menopausal symptoms and work-role related
      issues in a population-based sample of perimenopausal women. METHODS: All women
      aged 48 years and residing in the catchment area of the Karolinska Hospital were
      recruited through the Swedish population register. They received a questionnaire
      covering sociodemographic background, reproductive health and gynaecological
      characteristics, social and work role related issues as well as a symptom rating
      scale. RESULTS: Seventy percent of the women returned the questionnaire. Of
      these, 73% were premenopausal, 21% were postmenopausal and 6% were
      perimenopausal. Hormone replacement therapy was used by 7.5% of the respondents
      and the rate of hysterectomy was 8.6%. Regular exercise was reported by 44.4%.
      Factor analysis of the symptom ratings yielded four independent dimensions:
      Negative Moods, Vasomotor symptoms, Decreased Sexual Desire and Well-being.
      Multiple regression analyses showed that only vasomotor symptoms were
      significantly related to menopausal status. Negative Mood and Reduced Sexual
      Interest were better explained by the presence of vasomotor symptoms and by
      reproductive health and lifestyle variables such as current or previous PMS,
      dysmenorrhea, smoking and lack of exercise. CONCLUSIONS: Only vasomotor symptoms
      were significantly related to menopausal status. Psychosocial and lifestyle
      variables as well as past or current reproductive health are more important
      determinants of women's psychological well-being during transition to menopause
      than menopausal status.

PMID- 7715462
TI  - Menopause and perceived health status among the women of the French GAZEL cohort.
AB  - The aim of this study was to evaluate the effect of menopause on women's quality
      of life. Women (1171) aged from 45-52 years who work for the French national gas
      and electricity company volunteered for this study (response rate 75%). They
      completed a self-administered questionnaire pertaining to general health. Quality
      of life was measured by the Nottingham Health Profile (NHP). Within this group
      289 women were postmenopausal. After controlling for age, those women were more
      likely to show a lower quality of life than women still menstruating for 4 of the
      6 sections of the NHP: social isolation (odds ratio 1.4; 95% confidence interval
      1.1-1.9), pain, sleep and energy (odds ratios 1.5; 95% confidence intervals 1.1
      2.0). Those alterations of quality of life are explained by the climacteric
      complaints the women report. Those findings suggest that the treatment of
      menopausal symptoms with medication of proven efficacy may prevent lowering of
      quality of life due to menopause.

PMID- 7715463
TI  - Changes in Australian women's perception of the menopause and menopausal symptoms
      before and after the climacteric.
AB  - The symptoms and perceptions of menopause of 60 Australian women were studied, by
      questionnaire, when they were premenopausal and 10 years later when they were
      postmenopausal. Menopausal symptoms expected and experienced by the women were
      compared, fewer women experiencing hot flushes, headache, depression and
      nervousness and more experiencing insomnia, increase in appetite, abdominal
      fullness, numbness and muscular problems. The symptoms women thought were due to
      hormonal changes at menopause were compared. In 1993 more women cited
      osteoporosis, insomnia, loss of libido, obesity and loss of muscle tone as due to
      hormone change while fewer cited depression. The premenstrual symptoms and their
      severity experienced by a woman when she was premenopausal significantly predicts
      the type and severity of the menopausal symptoms experienced by the woman. The
      expected menopausal symptoms and their severity cited by a woman also
      significantly predicts the type of severity of the menopausal symptoms
      experienced. More premenstrual symptoms predict the menopausal symptoms than
      those menopausal symptoms the women expected. The expectation menopause will be
      'a relief' or 'a nuisance' significantly predicted the overall menopause
      experience described by the women. Their negative attitudes about doctors'
      understanding and information available about menopause remained unchanged but
      they forget menstrual cycle problems over the 10 years. The results suggest a
      possible physiological basis for premenstrual and menopausal symptoms. Assistance
      for women with their premenstrual and menstrual cycle symptoms may improve their
      quality of life at menopause.

PMID- 7715464
TI  - Estrogen and urinary incontinence in women.
AB  - OBJECTIVE: The purpose of this study was to review the efficacy of estrogen
      therapy for urinary incontinence by examining published trials and to review the
      epidemiologic and physiologic evidence for its action. DATA SOURCES: Controlled
      and uncontrolled trials of estrogen therapy in the English literature were
      collected. Eight controlled and 14 uncontrolled trials were identified. METHODS
      OF STUDY SELECTION: Trials were selected if they were prospective. All types of
      estrogen treatment were included. All types of outcome measurements were
      included. DATA EXTRACTION AND SYNTHESIS: Trials were categorized by type of
      estrogen used; outcome variables (subjective improvement vs objective urodynamic
      data); and cure/improvement rates. CONCLUSIONS: Published trials do not support
      estrogen replacement as efficacious therapy for stress urinary incontinence. It
      may be useful for incontinence associated with urgency and frequency. Adequately
      large controlled trials that evaluate estrogen replacement regimens used in the
      USA remain to be done.

PMID- 7715465
TI  - Use of a new transdermal delivery system for estrogen replacement therapy in
      postmenopausal women.
AB  - This study reports on the use of a new transdermal delivery system for estrogen
      replacement therapy. This was a 12 week open multicenter trial using patches that
      delivered 0.05 mg/24 hour of 17 beta-estradiol applied twice weekly, every 72
      hours, with one week interval after each 3 weeks. Results indicate an overall
      significant improvement on climacteric complaints with a highly significant and
      time-related reduction in the two most frequent symptoms: hot flushes and night
      sweating. Neither local nor systemic side effects were prevalent. By the end of
      treatment mean plasma levels of estradiol and FSH were 50.6 pg/ml and 46.8
      mIU/ml, respectively. It is concluded that this new system of transdermal
      estrogen replacement therapy significantly reduces the main postmenopausal
      symptoms, produces adequate plasma estradiol levels and allows good compliance to
      treatment.

PMID- 7715466
TI  - Antagonism of oestrogen-induced prolactin release by medroxyprogesterone acetate.
AB  - Previous studies conducted at our clinic suggested that the administration of
      hormone replacement therapy (HRT) in postmenopausal women could result in the
      inhibition of oestrogen-induced prolactin (PRL) release. The aim of this study
      was to determine how the pituitary function is affected by the sequential
      addition of medroxyprogesterone acetate (MPA) to oestrogen replacement therapy.
      Twenty-one postmenopausal women receiving no other medication were treated with a
      standard dose (0.625 mg/day) of conjugated equine oestrogens (CEE) for a period
      of 24 days, plus 5 mg/day MPA added sequentially during the last 12 days of the
      oestrogen therapy. Blood samples were collected before treatment, during
      oestrogen and oestrogen-progestogen administration and after cessation of
      treatment. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta
      oestradiol (E2) and PRL levels were studied. During treatment gonadotrophin
      concentrations decreased significantly, while after cessation of HRT the levels
      of FSH and LH increased. These gonadotrophin fluctuations indicated a sharp rise
      in E2 levels during therapy and a significant decrease during the treatment-free
      period. PRL levels were found to be higher during CEE therapy, but they fell when
      patients received CEE in combination with MPA. These observations suggest that
      the role of progestogens in a variety of experimental and clinically relevant
      situations needs to be investigated not only as regards their direct action but
      also their modulation of the effect of oestrogen.

PMID- 7715467
TI  - The role of prolactin in the menopause.
AB  - Within a study on menopausal discomforts, 2322 women were seen for the first time
      at the Outpatients Department for Climacteric Disturbances and Prophylaxis of
      Osteoporosis at our clinic. Amongst routine hormonal examination we measured
      prolactin levels. We found hyperprolactinemia in 23 women. Furthermore, in 224
      women who initially had normal hPRL values, an estrogen-gestagen replacement
      therapy was administered and within this we found a significant increase of the
      prolactin levels (P < 0.005). The role of prolactin in the climacteric period as
      well as the mechanism of the estrogen effect upon prolactin secretion are
      subjects of discussion.

PMID- 7715468
TI  - Inhibition of 17 beta-estradiol metabolism by grapefruit juice in ovariectomized
      women.
AB  - In an open, randomized, cross-over study the concentrations of 17 beta-estradiol
      and estrone in serum were measured over 192 hours in 8 ovariectomized women after
      a single oral dose intake of 2 mg micronized 17 beta-estradiol. The subjects were
      studied with and without grapefruit juice intake containing the three natural
      flavonoids, naringenin, quercetin and kaempherol, which are found as glycosides
      in citrus fruit. These flavonoids interact with the metabolism of drugs such as
      17 beta-estradiol and other steroids that are extensively metabolised through the
      P-450NF (P-450 IIIA4) enzyme or closely related P-450 systems. After
      administration of grapefruit juice, peak estrone (between 2-6 hours after tablet
      intake) concentrations increased significantly. The AUC0-48 and AUC0-192 for
      estrone but not 17 beta-estradiol, resulting from a single administration of
      micronized 17 beta-estradiol, were significantly altered. Combined measured
      estrogens (i.e. 17 beta-estradiol and estrone) also increased significantly. The
      relationship between the AUCs for 17 beta-estradiol and estrone was not altered
      by juice intake indicating that a metabolic step after estrone, i.e. further A
      and/or D ring conversion was inhibited. This study demonstrates that grapefruit
      juice may alter the metabolic degradation of estrogens, and increase the
      bioavailable amounts of 17 beta-estradiol and its metabolite estrone, presumably
      by affecting the oxidative degradation of estrogens. This food interaction may be
      one factor behind the interindividual variability in 17 beta-estradiol, estrone
      and estriol serum concentrations after exogenous administration of 17 beta
      estradiol to patients.

PMID- 7715469
TI  - Endocrine effects in Asian postmenopausal women treated with SH D 461 M and
      Prempak-C.
AB  - We reported the results of a randomized cross-over study comparing SH D 461 M
      (Climen) and Prempak-C in 38 postmenopausal women who were established users of
      hormone replacement therapy (HRT). Climen contains 11 tablets of 2 mg estradiol
      valerate (EV), and 10 tablets with 2 mg EV plus 1 mg of cyproterone acetate.
      Prempak-C, on the other hand, is a regime consisting of 28 tablets of 0.625 mg
      conjugated equine estrogens (CEE); the last 12 tablets are taken together with
      0.15 mg of norgestrel (NG) tablets. Patients in Sequence I started with Climen
      for 6 months and then crossed-over to Prempak-C, for the next 6 months; patients
      in Sequence II, followed the reverse order. Following Climen treatment,
      significantly higher levels (P < 0.05, t-test) of sex hormone binding globulin
      (SHBG) and estradiol, when compared to Prempak-C treated subjects, were noted. No
      significant differences in follicle stimulating hormone (FSH), corticosteroid
      binding globulin (CBG), renin, angiotensinogen, angiotensin-I and aldosterone
      levels between the two treatment regimes were noted. While both regimes were
      effective in reducing menopausal symptoms, none of the regimes could eliminate
      all symptoms completely. Treatment with Climen appeared to result in less
      frequent occurrences of some symptoms. During periods of no estrogen (only true
      for Climen) as well as periods of maximum progestagen and estrogen (P and E),
      subjects on Climen had significantly lower incidence of some of the symptoms
      (backache, lack of concentration, lethargy and swelling) when compared to those
      on Prempak-C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715471
TI  - Transvaginal ultrasonography for identifying endometrial pathology in
      postmenopausal women.
AB  - The objective of this study was to evaluate the usefulness of transvaginal
      ultrasonography in postmenopausal women with a clinical indication for a
      dilatation and curettage (D&C). Of the 167 postmenopausal women included in the
      study, 88% were referred for a D&C because of vaginal bleeding and 12% of the
      women had other clinical indications such as myomas, gynecological pain or
      suspected gynecological tumors. Hormone replacement therapy (HRT) was used by 37%
      of the women. The women were examined with transvaginal ultrasonography before
      the D&C. The endometrial thickness and texture were used as indicators of
      endometrial abnormalities. The ultrasonographical findings were related to the
      histological diagnosis obtained from the D&C. Histologically, 31% of the women
      had an atrophic endometrium and the corresponding ultrasonographically mean
      endometrial thickness was 4.6 mm (range 0-14 mm). Endometrial cancer was
      histologically found in 10% of the women and the endometrial thickness of the
      malignant endometrium, measured by ultrasonography, was 13.9 mm (range 6-31 mm).
      All the malignancies were found in the group of women with vaginal bleeding, but
      only one was in the group of women on HRT. Histologically, endometrial
      hyperplasia was found in 6.5% of the women and endometrial polyps in 8.5% after
      the D&Cs. In these postmenopausal women it was demonstrated that if the
      endometrium was < 6 mm thick, no endometrial cancer was found at
      histopathological investigation. By using a cut-off point of 6 mm of
      ultrasonographically measured endometrial thickness for identification of
      endometrial pathology in our study, at least 50% of the D&Cs could be spared.

PMID- 7715470
TI  - Changes in the withdrawal bleeding pattern and endometrial histology during 17
      beta-estradiol-dydrogesterone therapy in postmenopausal women: a 2 year
      prospective study.
AB  - OBJECTIVE: To describe changes in the withdrawal bleeding pattern and endometrial
      histology during a sequential 17 beta-estradiol-dydrogesterone regimen in
      postmenopausal women. DESIGN: Open-label, non-comparative, prospective study.
      SETTING: Gynecological outpatient department of a university hospital. PATIENTS:
      Twenty-seven healthy non-hysterectomized postmenopausal women. INTERVENTIONS:
      Continuous micronized 17 beta-estradiol supplementation, 2 mg daily, and cyclic
      administration of dydrogesterone, 10 mg daily for the first half of each 28 day
      treatment cycle. MAIN OUTCOME MEASURES: Changes in the characteristics of the
      withdrawal bleeding pattern and the endometrial biopsy histology during 2 years
      of treatment. RESULTS: The initial withdrawal bleeding was comparable to normal
      menstruation with respect to amount and duration. During the 2 years of treatment
      the bleeding showed a significant tendency to become shorter with less blood
      loss. This was mainly the result of the decrease (P < 0.001) in the number of
      days per cycle with bleeding grade II (normal menstruation). None of the women
      developed endometrial hyperplasia, and in almost all women the given hormone
      replacement therapy regimen induced secretory or atrophic changes of the
      endometrium. CONCLUSIONS: This sequential 17 beta-estradiol-dydrogesterone
      regimen can be regarded as safe with respect to the prevention of endometrial
      disease and appeared to foster patient compliance.

PMID- 7715472
TI  - Endometrial hyperplasia: efficacy of a new treatment with a vaginal cream
      containing natural micronized progesterone.
AB  - Seventy-eight premenopausal women affected by benign endometrial hyperplasia (60
      simple and 18 complex) were treated from the 10th to the 25th day of the
      menstrual cycle with a vaginal cream containing 100 mg of natural micronized
      progesterone in polyethylene glycol base. The treatment lasted 3 months in 58
      patients and 6 in the other 16 patients. Four patients were lost from the study.
      We observed a total of 67 complete regressions (90.5%) of which 58 (78.3%)
      occurred in the first 3 months and 9 (11.5%) after 6 months of treatment. Simple
      hyperplasia showed a significantly higher response to treatment in comparison
      with the complex type (P < 0.001). The most frequent endometrial pattern detected
      in the patients in whom hyperplasia regressed was of a secretive type. Recurrence
      of hyperplasia occurred in 1 out of 58 (1.72%) patients at the 3rd month and in 3
      out of 49 (6.1%) patients at the 6th month after treatment. There were no
      significant differences between the two hystological groups in the percentage of
      recurrence. During treatment we observed a significant reduction of the amount,
      duration and frequency of the menstrual bleeding. Minimal side-effects were
      observed. In conclusion, for its effectiveness and safety, vaginal administration
      of natural micronized progesterone seems to be an interesting approach to benign
      endometrial hyperplasia, particularly indicated in women also affected by
      metabolic disorders.

PMID- 7715473
TI  - Determinants of forearm mineral density and its correlation with fracture history
      in women.
AB  - In order to evaluate the role of single photon absorptiometry (SPA) in the
      prediction of osteoporotic fracture risk, 1935 women, referred for measurement of
      forearm mineral density (FMD) at the distal radial site, were studied by
      questionnaire in a cross-sectional design. There was no significant decline in
      FMD until the age of 47, after which there was a linear decline with age of about
      1.2% per year. There was no relationship between age and FMD, or forearm mineral
      content (FMC), in premenopausal women. There was a fall in FMD with the number of
      years since menopause, after correcting for the effects of age, of approximately
      0.5% per year. Body weight was positively correlated with FMC in postmenopausal
      women. The duration of exposure to hormone replacement therapy (HRT) was
      positively correlated with FMD, and the magnitude of this effect was reduced the
      longer the delay between the onset of the menopause and the commencement of HRT.
      There was no significant association of FMD with calcium intake, weight-bearing
      exercise, tobacco or alcohol consumption, or family history of osteoporosis. FMD
      was significantly lower in postmenopausal women who reported fractures after the
      age of 25, after correcting for age and years postmenopause. In conclusion, a low
      FMD is predictive of a past history of fractures and may therefore be capable of
      predicting future fracture risk.

PMID- 7715474
TI  - Effects of percutaneous oestradiol versus oral oestrogens on bone density.
AB  - In order to compare the effects on bone density of 1.5 mg/day percutaneous 17
      beta-oestradiol (E2) and of 0.625 mg/day oral conjugated oestrogens (CEE), 68
      women who had undergone hysterectomy were studied. The subjects were randomly
      allocated to one of three study groups. A total of 15 women dropped out from
      these groups during the study. The percutaneous group (n = 20) received treatment
      for 36 months and the oral group (n = 17) for 24 months, while the untreated
      group (n = 16) served as controls over a period of 24 months. Bone mineral
      density (BMD) was measured by dual gammagraphic densitometry (Novo 22A
      densitometer) in the lumbar spine (L2-L4). The percentage gain in the
      percutaneous group was 1.7% +/- 3.9% after 12 months, 5.6% +/- 2.9% (P < 0.001)
      after 24 months and 4.7% +/- 3.2% (P < 0.01) after 36 months. In the oral group
      the gain was 3.5% +/- 13.0% after 12 months and 4.3% +/- 9.2% (P < 0.001) after
      24 months. In the untreated group the bone density loss was 6.6% +/- 3.5% (P <
      0.001) after 12 months and 9.1% +/- 3.4% (P < 0.001) after 24 months. On the
      basis of our results we concluded that both 1.5 mg/day percutaneous E2 and 0.625
      mg/day oral CEE not only prevented bone loss but also increased BMD, as was
      confirmed by our findings after 36 and 24 months of treatment, respectively.

PMID- 7715475
TI  - Effects of tibolone on lipoprotein(a) and HDL subfractions.
AB  - OBJECTIVE: To determine the effects of tibolone, a synthetic steroid used to
      alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein
      metabolism, with particular reference to lipoprotein(a) levels and HDL
      subfraction profiles. DESIGN: Thirty nine postmenopausal women were treated with
      tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels
      were estimated at 0, 2, 4 and 6 months. RESULTS: Lipoprotein(a) levels were
      reduced significantly over the 6 months from a median level of 245 (range < 60
      780) mg/l to 152 (range < 60-530) mg/l, a reduction of 39% in the median level. A
      decrease was observed in approximately two thirds of the women. Reductions were
      noted in all 6 subjects whose pretreatment levels were high, although
      concentrations remained at a level associated with increased risk in all but one.
      There were significant decreases in triglycerides and VLDL cholesterol and no
      significant change in LDL cholesterol. There was a significant reduction of 18%
      in HDL cholesterol and a 26% reduction in the HDL2-HDL3 ratio. CONCLUSION: The
      reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular
      risk, which could go some way towards balancing the potentially adverse effect on
      the cardiovascular system caused by the reduction in HDL cholesterol.

PMID- 7715476
TI  - Do psycho-social factors contribute more to symptom reporting by middle-aged
      women than hormonal status?
AB  - Six hundred women aged between 45 and 54 were randomly selected from the
      electoral roll in Brisbane, Australia. A questionnaire addressing their symptoms,
      hormone status and psycho-social factors was successfully administered to 381
      women (64% of the original sample; 83% of those contactable). Although
      cardiovascular symptoms were experienced by 25% of the sample, the most common
      (hot flushes) ranked only tenth on a list of recently experienced symptoms. The
      association of hormone status with symptoms was weak in comparison with other
      factors. Most symptoms were reported by women who were perimenopausal, had
      undergone a hysterectomy, or were currently using hormone replacement therapy. A
      poor mental health index was strongly associated with all groups reporting
      symptoms. It is concluded that clinicians responding to symptoms from middle-aged
      women should continue to address psychosocial factors just as vigorously as those
      related to their hormone status.

PMID- 7715477
TI  - Physical activity and the menopause experience: a cross-sectional study.
AB  - A randomly selected community cohort of 2000 Australian born women aged 45 to 55
      were interviewed on the telephone and information obtained on their health and
      well-being. These women were divided into pre-, peri-, natural and surgical
      menopausal groups on their menstrual history. A physical activity questionnaire
      was sent to 1181 women in the first three of these groups. These questionnaires
      were completed and returned by 61.6% of the women. The response rate in all
      groups was significantly associated with the years of education, employment
      status, body mass index (BMI) and self-rated health of the participants. The aim
      of the study was to test the hypothesis that physical activity is a major
      contributor to health and well-being by establishing the relationships between
      physical activity and certain health outcomes, such as menopausal symptoms,
      psychological well-being, self-rated health and BMI in this cohort of mid-life
      women. The inter-relationship between physical activity and other variables,
      including menopausal status, interpersonal stress, health related and preventive
      health behaviours was examined. Levels of physical activity were significantly
      associated with better self-rated health, lower BMI measurements, moderate
      alcohol intake and self-breast examination. There was no significant association
      between levels of physical activity, psychological well-being and women's
      experience of symptoms during the natural menopause transition.

PMID- 7715478
TI  - Determinants of first prescription of hormone replacement therapy. A follow-up
      study among 1689 women aged 45-60 years.
AB  - The aim of the present study was to ascertain the cumulative incidence of first
      hormone replacement therapy (HRT) and the factors that predict its prescription.
      In a general population 1689 women were followed for 9 months in order to trace
      first HRT prescriptions. Determinants (well-being, attitude towards menopause,
      menopausal status and another 9 variables) were measured by means of a
      questionnaire. Data analyses were performed for all women and for women with or
      without typical climacteric complaints. The cumulative 9 month incidence of HRT
      was 6.2%. For women without typical complaints a lower level of well-being (odds
      ratio 5.5; 95% CI 1.9-15.5) and the former use of the contraceptive pill (odds
      ratio 4.6%; 95% CI 1.0-20.5) were independently associated with HRT prescription.
      For women with typical complaints a positive attitude towards 'menopause should
      be treated' (odds ratio 3.8; 95% CI 1.8-8.0) was a determinant of HRT
      prescription. The cumulative incidence of HRT prescription is high, but from
      additional data it is apparent that within a period of 1 year and 9 months the
      majority of women stop taking HRT. For women without typical complaints,
      physicians prescribe HRT five times more often to those with a lower level of
      well-being. For women with typical complaints the physician's prescription is
      primarily related to the woman's attitude towards (medical) treatment of the
      menopause.

PMID- 7715479
TI  - Compliance to hormone replacement therapy in menopausal women controlled in a
      third level academic centre.
AB  - Compliance to distinct combinations of hormone replacement therapy was assessed
      in 331 postmenopausal women treated for 1 to 5 years in the Menopause Unit of a
      third level referral Academic Hospital. Forty nine women (15%) had interrupted
      therapy, mainly during the first year, while 29 (9%) never had their
      prescriptions filled. Forty five women (14%) followed the treatment
      intermittently or only sporadically completed the treatment as prescribed. Four
      main factors were analyzed for their eventual influence on compliance: the
      inclusion of progestins in the prescription, the source of referral, the severity
      of menopause-induced symptomatology, and the route of estrogen administration.
      The source of referral divided women into three groups: patients referred from a
      doctor, those addressed from the gynecology ward of the hospital, and women who
      directly asked to be taken as patients in the unit. The intensity of clinical
      manifestations was assessed through the Kupperman index. Only two variables, the
      addition of progestins (P < 0.02), and the oral route of estrogen administration
      (P < 0.01) determined lower levels of compliance. The other two factors did not
      induce significant changes in the attitude of the patients towards hormone
      therapy.

PMID- 7715480
TI  - [Hydrophobic characteristics of the microorganism cell surface].
AB  - Hydrophobic properties of the surface of microorganism cells can be featured by
      parameters that define the equilibrium of cellular adsorption on liquid
      carbohydrates: constant of sorption equilibrium, a maximal number of adsorbable
      cells, as well as coefficient of cellular distribution (Kd) between liquid and
      organic phases that can be determined either with the equation of adsorption
      isotherm or experimentally. It is shown that the latter technique gives a more
      informative characteristics of the hydrophobicity levels in the surface of cells
      than the percentage of of hydrophobicity cited in literature. The results of this
      study can be used in the screening of microorganism strains and in the solvation
      of problems of industrial microbiology related to the fixation of cells on
      differently structured carriers.

PMID- 7715481
TI  - [The effect of Bacillus intermedius RNAase on the growth and development of
      Bacillus mucilaginosus].
AB  - The effect of Bacillus intermedius RNAase on vegetative cells and spores of
      siliceons bacteria Bacillus mucilaginosus was investigated. It is shown that the
      enzyme stimulates the growth of vegetative cells of B. mucilaginosus at a
      concentration of 10 mkg/ml and promotes germination of spores at a 1000-fold
      lesser concentration (0.1 mkg/ml). The spores at stages of activation and
      initiation appear to be most susceptible to the enzyme action. The effect of
      RNAase on B. mucilaginosus multiplication correlates with intensification of
      bacterial leaching of bauxites.

PMID- 7715482
TI  - [The role of amino acids in intensification of Bacillus subtilis
      exopolysaccharide biosynthesis in deep growth conditions].
AB  - The influence of various combinations of amino acids on the Bacillus subtilis
      growth activity and exopolysaccharide biosynthesis has been studied. The effects
      of amino acid additions on these two processes have appeared to be different. The
      strains reveal the specificity in amino acids requirements while cultivation in
      liquid media. To judge by the average indirect contributions, the growth as well
      as the exopolysaccharide biosynthesis of B. subtilis strain 39 have been
      significantly affected by introduction of alanine, valine, phenylalanine,
      tryptophane and glycine in triple combinations into the culture medium. The
      exopolysaccharide production and growth of B. subtilis strain 51 have been
      influenced markedly by methionine, leucine, isoleucine, cystine, glycine,
      tryptophane and alanine. Addition of different combinations of these amino acids
      makes it possible to obtain the 20.2-56.3% higher biomass amounts with the
      simultaneous 26.8-89.6% increase of exopolysaccharide yield.

PMID- 7715484
TI  - [Use of an immunodiffusion analysis method in micrococcus species determination].
AB  - Eight species of the genus Micrococcus were studied in details for their
      antigenic specificities with the aid of the created bank of specific polyclonal
      antisera to the type strains of Micrococcus Cohn 1872--M. luteus CCM 169, M.
      varians CCM 884, M. roseus CCM 679 and M. nishinomiyaensis CCM 2140.
      Immunochemical analysis of 146 strains isolated from various natural and
      industrial substrata, as well as of 31 collection strains allowed us to reveal
      antigenic relatedness and distinctions between studied cultures and to accomplish
      taxonomic distribution of various Micrococcus species. By the immunoduffusion
      analysis the intraspecific antigenic relationship of M. roseus and M. varians was
      found, as well as significant antigenic heterogeneity of M. luteus. The results
      of antigenic analysis of micrococci may be used in the collection work and for
      the express-diagnostics of these microorganisms.

PMID- 7715483
TI  - [Features of secretion of bacteriolytic enzymes and polysaccharides in bacteria
      from the Pseudomonadaceae family].
AB  - It is shown that secretion of bacteriolytic complex enzymes in a bacterium of the
      family Pseudomonadaceae begins in the latent and early logarithmic culture growth
      phases. A maximum of specific bacteriolytic activity falls in the same time
      interval with a maximum of specific activity of lytic proteinase L2 and
      muramidase. The activity of concomitant enzymes--non-specific proteinase and
      neutral phosphatase--peaks in the middle of the logarithmic growth phase.
      Secretion of exopolysaccharide into the external medium begins in the second half
      of the logarithmic growth phase and, thus, is not coordinated with secretion of
      bacteriolytic enzymes. It is shown that relative content of enzymes and
      polysaccharides depends upon the composition of growth medium for the producer.

PMID- 7715486
TI  - General practice budget holding: what can the United Kingdom teach Australia?

PMID- 7715485
TI  - [Halophilic archaebacteria from the Kalamkass oilfield].
AB  - Two strains of halophilic archebacteria, growing in the range from 10 to 25%
      NaCl, were obtained from the brines of the Kalamkass (Mangyshlak) oilfield. Both
      strains are extremely halophilic archaebacteria according to their total
      phenotypic properties. Strain M-11 was identified as Haloferax mediterranei on
      the basis of the composition of polar lipids and DNA-DNA homology. The
      composition of polar lipids and 16S rRNA sequences of M-18 strain permitted to
      include it in Haloferax genus. This strain differs from the affirmed species of
      Haloferax genus--H. volcanii and H. mediterranei. However, the additional
      investigations are necessary for its relation to new species.

PMID- 7715487
TI  - Control and elimination of tuberculosis in Australia.

PMID- 7715488
TI  - Tuberculosis in Australia, 1989-1992. Bacteriologically confirmed cases and drug
      resistance.
AB  - OBJECTIVE: To collate statistics, including drug susceptibility, of patients with
      bacteriologically confirmed tuberculosis in Australia during 1989-1992. DESIGN:
      Collaborative project among the five Australian mycobacterial reference
      laboratories. STUDY POPULATION: 2509 Australian residents with bacteriologically
      confirmed tuberculosis. OUTCOME MEASURES: Patient and specimen data, and drug
      susceptibility results recorded for isolates of Mycobacterium tuberculosis and
      Mycobacterium bovis. RESULTS: The annual incidence during 1989-1992 was about 3.6
      per 100,000. The male-to-female ratio was 1.4:1 and about half the patients were
      under 50. Older men had high rates of disease. Lymphatic disease was
      significantly more common in females; the converse was true for pulmonary and
      pleural disease. Resistance to at least one of the common antituberculosis drugs
      was detected in 14.4% of isolates, and usually involved streptomycin (7.6%) and
      isoniazid (8.4%). Fewer than 1% of isolates were resistant to isoniazid and
      rifampicin in combination. CONCLUSIONS: By international standards, Australia
      remains a "low-incidence" country for tuberculosis, with a static annual
      incidence. Multiple drug resistance is uncommon and most patients should respond
      to the standard four-drug regimen. Nevertheless, because clinical data confirm
      that the pool of infected persons is being supplemented through immigration, and
      that certain population subgroups have high rates of disease, it is essential
      that Australia maintain effective control programs.

PMID- 7715489
TI  - An outbreak of Barmah Forest virus disease in the south-west of Western
      Australia.
AB  - OBJECTIVES: To describe the first reported outbreak of Barmah Forest (BF) virus
      disease in the south-west of Western Australia. DESIGN: Case series correlated
      with results of arbovirus surveillance. All patients with clinically suspected
      Ross River (RR) virus infection were serologically tested for antibodies to BF
      and RR viruses. Home address and date of presentation of patients with
      serologically confirmed recent infection were recorded. Mosquitoes collected from
      the districts before and during the BF virus outbreak were identified to species
      level and tested for virus. RESULTS: Twenty-two cases of BF disease were reported
      from the region between August 1992 and March 1994. Most occurred in the Peel
      region in the spring and early summer of 1993. Eighteen isolates of BF virus were
      obtained from three different species of mosquito trapped between January and
      October 1993. Fifteen were from mosquitoes in the Peel region and a single
      isolate was from the Perth metropolitan area. No isolates were obtained from the
      region before 1993. RR virus was not isolated from mosquitoes trapped in the
      region during the BF virus outbreak. CONCLUSIONS: Most BF infections were
      acquired in the Peel region during spring and early summer of 1993. Aedes
      camptorhynchus mosquitoes were probably the main vectors. The lack of isolations
      from mosquitoes before 1993 suggests that the virus may have only recently been
      introduced (or reintroduced) to the region. It was transmitted under conditions
      that were apparently not conducive to transmission of RR virus.

PMID- 7715490
TI  - Improving outcome for Western Australian infants with birthweights 500-999 g.
AB  - OBJECTIVE: To assess changes in survival and disability in liveborn extremely low
      birthweight infants (500-999 g) in Western Australia, 1980-1987. DESIGN: Cohort
      study comparing two periods, 1980-1983 (P1) and 1984-1987 (P2). PARTICIPANTS: All
      586 liveborn extremely low birthweight infants in WA in 1980-1987 (266 in P1, 320
      in P2). MAIN VARIABLES EXAMINED: Birthweight, place of birth, age at death,
      neurosensory examination findings and scores on the Griffiths Mental Development
      Scales or other standardised test results. RESULTS: 482/586 infants (82%) were
      born at King Edward Memorial Hospital (KEMH), a level III referral centre, and a
      further 4% were transferred there after birth. The proportion born at KEMH
      increased from 78% in P1 to 86% in P2. Survival increased from 35% to 43%
      overall. In those below 800 g birthweight, survival doubled from 14% to 29%.
      There was no change in the age at death for non-survivors. Follow-up information
      was known for 222 of the 229 survivors at median ages of 46 months (P1) and 43
      months (P2). Disability rates in infants below 800 g birthweight remained static
      (P1, 26%; P2, 28%), but fell in those of 800-999 g birthweight from 24% to 13%.
      Overall, survival free of disability increased from 26% to 34%. CONCLUSION:
      Increased survival rates occurred without any increase in the rate or severity of
      disability in survivors.

PMID- 7715491
TI  - Are medication record cards useful?
AB  - OBJECTIVE: To assess the use of patient-held medication record cards and their
      acceptability to patients and doctors. DESIGN: Prospective 12-month study with
      data collection at baseline and on three subsequent occasions at four-monthly
      intervals. PATIENTS AND SETTING: 187 patients with a mean age of 78.4 years
      (range, 60-101) were taking a mean of 5.8 medications each (range, 1-18). They
      lived on Sydney's lower north shore and were able to care for themselves. MAIN
      OUTCOME MEASURES: Availability of card on request, frequency of use, status of
      recorders and accuracy of records (checked by inspection of medications at home).
      RESULTS: Most patients retained their cards, but the proportion who presented it
      to their doctor fell from 61% to 23% over the 12 months (P < 0.0001), and the
      proportion with accurately recorded drug regimens ranged from 20% down to 16%. Of
      the 75 regimens written exclusively by general practitioners in the 12 months,
      only 19 (25%) were consistent with what the patients were actually taking.
      CONCLUSION: Medication record cards introduced into the doctor-patient
      relationship by a "third-party" are unlikely to result in better quality use of
      medicines.

PMID- 7715492
TI  - Hepatitis B vaccination rates among staff at a district general hospital.
AB  - OBJECTIVE: To evaluate the uptake of hepatitis B vaccination by staff of a
      metropolitan district general hospital and associated community health service in
      order to determine if the existing vaccination program was adequate. DESIGN,
      SETTING AND PARTICIPANTS: A cross-sectional survey of all 1464 staff of a 304-bed
      district general hospital and associated community health service, serving a
      population of approximately 240,000 people in a middle socioeconomic area of
      northern Sydney, by means of a self-reported anonymous questionnaire. RESULTS:
      The overall response rate was 56.4%, with 61.9% of high-risk and 48.7% of low
      risk staff responding to the survey. The overall vaccination rate was 55.8%. Of
      high-risk respondents, 70.7% had been or were in the process of being vaccinated,
      compared with 29.4% of low-risk respondents. Of those already vaccinated, only
      45.9% had subsequently been tested for antibody to hepatitis B surface antigen
      (anti-HBs); 12% of this group did not know whether their response to the vaccine
      had been adequate and 18% reported being advised to have another anti-HBs test
      later. Vaccination rates were higher in younger staff (68.7% of 20-29-year-olds)
      than in older staff (42.7% of 50-59-year-olds). There was no significant
      difference in vaccination rates between men (55.6%) and women (55.8%).
      Vaccination rates for doctors, dentists and nurses were 69%, 80% and 74.6%,
      respectively. CONCLUSION: The vaccination rate among high-risk staff is
      suboptimal: more than half did not know whether their vaccination had induced a
      suitable level of antibodies; more than 10% had been vaccinated more than five
      years previously; and 5% had not completed the full course of three injections.
      High-risk staff should be targeted in future vaccination programs.

PMID- 7715493
TI  - Effectiveness of doxycycline combined with primaquine for malaria prophylaxis.
AB  - OBJECTIVE: To assess the causal prophylactic activity (activity against the pre
      erythrocytic liver stage) of a daily regimen of doxycycline combined with low
      dose primaquine against malaria in Australian Defence Force personnel deployed to
      Papua New Guinea (PNG). PARTICIPANTS AND SETTING: A 53-strong Australian Army
      engineer detachment deployed to the north coast of PNG for 42 days starting in
      July 1993. INTERVENTIONS: The soldiers took doxycycline (100 mg) and primaquine
      (7.5 mg) daily, starting at least two days before they entered the endemic area
      and continuing for three days after their return to Australia. No primaquine
      eradication course was given at that time. MAIN OUTCOME MEASURES: The number of
      soldiers who developed malaria, plasma drug concentrations and drug side effects.
      RESULTS: None of the 53 men developed malaria while in PNG. Three developed
      falciparum malaria two to three weeks after leaving the endemic area, although
      one of them had taken doxycycline alone because of glucose-6-phosphate
      dehydrogenase deficiency. Nine men developed vivax malaria between three and 40
      weeks after leaving PNG, and three had relapses. Doxycycline was generally well
      tolerated, with only three of the men requiring a change of medication to
      mefloquine because of adverse gastrointestinal symptoms. CONCLUSIONS: Although
      doxycycline generally provides good protection against malaria infection, it
      cannot be relied on for causal prophylaxis, even when combined with low dose
      primaquine. Because the malaria infections occurred only after return to
      Australia, doxycycline appears to be effective in suppressing malaria while the
      drug is being taken. Intense, repeated exposure to malaria may require an
      extended period of chemoprophylaxis on return from an endemic area.

PMID- 7715494
TI  - Delayed referral of patients with aneurysmal subarachnoid haemorrhage.
AB  - OBJECTIVE: To determine the outcome of patients with subarachnoid haemorrhage and
      whether delays in their diagnosis and referral have been reduced over a 15-year
      period. DESIGN: A 15-year retrospective study of patients admitted to a tertiary
      neurosurgical unit between 1977 and 1992. SETTING: The Royal North Shore
      Hospital, Sydney. PATIENTS: 511 patients admitted with subarachnoid haemorrhage
      from ruptured intracranial aneurysms. RESULTS: Of 486 patients with at least a
      six-month follow-up, 66% made a good recovery and 19% died. Outcome was
      significantly influenced by the neurological condition of the patient at
      admission (P < 0.0001). There was no significant difference in the relative
      proportions of patients transferred late (three or more days after onset of
      symptoms) when those admitted before and after 1986 were compared. CONCLUSION:
      Delayed diagnosis and referral remain the major preventable problems in the
      management of patients with aneurysmal subarachnoid haemorrhage.

PMID- 7715495
TI  - Lack of evidence for significant hepatitis B transmission in Australian Rules
      footballers.
AB  - OBJECTIVE: To determine the prevalence of markers of past hepatitis B infection
      among participants in Australian Rules football, to estimate the potential
      exposure of Australians to hepatitis B virus (HBV) in contact sport. DESIGN AND
      SETTING: A point prevalence survey for antibody to hepatitis B surface antigen
      (anti-HBs) and core antigen (anti-HBc), supported by a questionnaire used to
      determine the history of risk and exposure, in South Australian National Football
      League (SANFL) players supervised at club level by general practitioners and
      sports medicine specialists. PARTICIPANTS: Of 245 players from seven clubs, 49
      were excluded from the study because they had been previously vaccinated. Of 196
      eligible participants, 117 submitted blood samples and, of these, 85 returned
      questionnaires. RESULTS: One player was positive for anti-HBc (a prevalence rate
      of 0.85%). This individual and three anti-HBc-negative players were positive for
      anti-HBs in the absence of a history of vaccination. We could not ascertain
      whether these additional three players had been previously infected, or
      vaccinated without this fact having been recorded on the questionnaires. No
      single behavioural factor correlated with positive anti-HBs results. CONCLUSIONS:
      The prevalence of markers of past hepatitis B infection in SANFL football players
      was no different to that in blood donors of the same age group from the same
      city. There was no evidence for any additional HBV transmission due to
      participation in football over that in the blood donor population. Vaccination of
      footballers and people engaged in similar sports is of benefit in conferring
      protection on the individual, but would be unlikely to make a significant public
      health impact on community rates of HBV infection.

PMID- 7715496
TI  - Infectious diarrhoea revisited.

PMID- 7715497
TI  - Locally acquired hepatitis E in the Northern Territory of Australia.

PMID- 7715498
TI  - A critical incident study of general practice trainees in their basic general
      practice term.
AB  - OBJECTIVE: To obtain information on the experiences of general practice (GP)
      trainees during their first general practice (GP) attachment. DESIGN: Critical
      incident technique--a qualitative analysis of open-ended interviews about
      incidents which describe competent or poor professional practice. SUBJECTS:
      Thirty-nine Western Australian doctors from the Royal Australian College of
      General Practitioners' (RACGP) Family Medicine Program who were completing their
      first six months of general practice in 1992. RESULTS: Doctors reported 180
      critical incidents, of which just over 50% involved problems (and sometimes
      successes) with: difficult patients; paediatrics; the doctor-patient
      relationship; counselling skills; obstetrics and gynaecology; relationships with
      other health professionals and practice staff; and cardiovascular disorders. The
      major skills associated with both positive and negative critical incidents were:
      the interpersonal skills of rapport and listening; the diagnostic skills of
      thorough clinical assessment and the appropriate use of investigations; and the
      management skills of knowing when and how to obtain help from supervisors,
      hospitals and specialists. Doctors reported high levels of anxiety over difficult
      management decisions and feelings of guilt over missed diagnoses and inadequate
      management. CONCLUSION: The initial GP term is a crucial transition period in the
      development of the future general practitioner. An analysis of commonly recurring
      positive and negative critical incidents can be used by the RACGP Training
      Program to accelerate the learning process of doctors in vocational training and
      has implications for the planning of undergraduate curricula.

PMID- 7715499
TI  - Alcohol-related health problems in the elderly.
AB  - Alcohol misuse is common in the elderly, and the problem may be compounded by the
      body's reduced ability to metabolise ethanol and interactions with over-the
      counter and prescription drugs. Older heavy drinkers are likely to present with
      mental health problems--anxiety, depression, dementia, confusion and sleep
      disturbance--or physical problems--gait disturbance, falls and liver disease.
      Alcohol use must be accurately assessed, and physical, neurological and mental
      state examinations performed. Treatment should be individualised, with the
      patient's needs being matched to the treatment options available.

PMID- 7715500
TI  - Cardiac surgery.

PMID- 7715501
TI  - The meaning of overseas specialist training.

PMID- 7715502
TI  - The meaning of overseas specialist training.

PMID- 7715503
TI  - The meaning of overseas specialist training.

PMID- 7715504
TI  - Cushing's syndrome from an inhaled glucocorticoid.

PMID- 7715505
TI  - Delays in diagnosis of head and neck cancer.

PMID- 7715506
TI  - Amniocentesis to diagnose congenital cytomegalovirus infection.

PMID- 7715507
TI  - Changes in the investigation and management of primary operable breast cancer in
      Victoria.

PMID- 7715508
TI  - External jugular vein thrombosis: a complication of the ovarian hyperstimulation
      syndrome.

PMID- 7715509
TI  - Good seroconversion after a fourth hepatitis B vaccination in aboriginal
      children.

PMID- 7715510
TI  - The ethics of patenting medical treatment.

PMID- 7715512
TI  - Is cardiomyoplasty an alternative to cardiac transplantation?

PMID- 7715511
TI  - Failures in screening for cervical cancer: who is to blame?

PMID- 7715513
TI  - Predicting outcomes in thoracic outlet syndrome.
AB  - OBJECTIVE: To test the hypothesis that somatosensory evoked potentials (SEP) and
      results of arterial photoplethysmography (PPG) predict outcome after surgery for
      thoracic outlet syndrome. DESIGN: A retrospective case series which correlated
      surgical outcome with preoperative SEP and PPG results using Fisher's exact test.
      PPG results were considered abnormal when there was complete loss of arterial
      pulsation, and SEP results when amplitudes were reduced and latencies delayed.
      SETTING: Royal Prince Alfred Hospital, between March 1984 and February 1992.
      PATIENTS: Forty-six consecutive patients with clinically diagnosed thoracic
      outlet syndrome were admitted for surgery; sixteen underwent bilateral operations
      (total of 63 limbs). INTERVENTIONS: After SEP and PPG tests, all patients
      underwent thoracic outlet decompressive surgery--excision of the first rib, of
      the cervical rib (where present), and of other congenital anomalies associated
      with thoracic outlet syndrome--by the axillary approach. MAIN OUTCOME MEASURES:
      Surgical outcome was graded as good when symptoms improved and the patient
      returned to work or pre-illness activities. It was graded as poor when symptoms
      remained unchanged or worsened, or when there was continued inability to work or
      engage in usual activities. RESULTS: The follow-up period ranged from 1.9-9.8
      years (mean, 5.7 years). Significantly more limbs with abnormal SEP or PPG
      results had a good outcome (49 of 53 limbs; 93%) than limbs with normal SEP and
      PPG results (six of 10 limbs; 60%) (P = 0.02). CONCLUSIONS: Abnormal SEP and PPG
      results correlated with a better postsurgical outcome. These tests may therefore
      aid in determining prognosis of surgery for thoracic outlet syndrome.

PMID- 7715514
TI  - Gynaecological care of women with abnormal Pap smears: how varied is current
      practice?
AB  - OBJECTIVE: To assess the current management by gynaecologists of women with
      abnormal Papanicolaou (Pap) smears. DESIGN: Self-administered survey of all
      gynaecologists registered in New South Wales. RESULTS: 242 gynaecologists (73%
      response rate) returned completed questionnaires. Accredited laboratories were
      used by 90% of gynaecologists, but only 61% could confirm their laboratories'
      participation in quality assurance procedures. Consensus on the management of
      high grade Pap smear abnormalities was confirmed. In contrast, there was
      considerable variation in the management of minor lesions, provision of patient
      information and follow-up after treatment. A small but worrying minority of
      respondents indicated an apparent misunderstanding of important colposcopic
      principles: 41% were prepared to institute ablative therapy without histological
      diagnosis. CONCLUSIONS: Given the nature of practice variation documented in this
      survey, publication of national guidelines is necessary to improve the screening
      program. Guidelines in themselves, however, will not be sufficient to ensure that
      all women with abnormal results of Pap smears receive appropriate and timely
      management and follow-up. Active dissemination to reduce undesirable variation is
      required.

PMID- 7715515
TI  - Risk factors and predictors of outcome in an Australian cohort with hepatitis C
      virus infection.
AB  - OBJECTIVES: To define demographic and epidemiological features of an Australian
      population with chronic hepatitis C virus (HCV) infection and determine
      predictors of histological and clinical outcome. DESIGN: Cohort study. PATIENTS
      AND SETTING: 342 consecutive HCV antibody-positive patients referred to the liver
      clinic of a major metropolitan general hospital. OUTCOME MEASURES: Demographic
      data, serial alanine aminotransferase (ALT) levels, full blood count for all
      patients. Percutaneous liver biopsy in 152 patients (44%). RESULTS: 51% of
      patients had previously used injecting drugs, 15% had received a blood
      transfusion and 27% had no definite percutaneous risk factor (sporadic group).
      The injecting drug users (IDUs) were younger and more likely to have been born in
      Australia. The sporadic group were older and frequently were born in
      Mediterranean or Asian countries. A history of excessive alcohol use was common,
      particularly among IDUs (60%). Of 152 patients who had a liver biopsy, 49 had
      cirrhosis and 103 had chronic hepatitis. Some patients with a normal ALT level
      had marked necro-inflammatory activity. On univariate analysis, the presence of
      cirrhosis correlated with older age (P < 0.0001), lack of an identifiable risk
      factor (P < 0.001) and birth in a Mediterranean or Asian country (P < 0.0001). On
      multivariate analysis, the only significant predictor of cirrhosis was age (P <
      0.001). Among patients with an identifiable percutaneous risk factor, cirrhosis
      was seen at a median time of 18 years after first exposure to risk, compared with
      13 years in patients with chronic hepatitis (P < 0.01). Patients with clinical
      evidence of portal hypertension were, on average, 15 years older than those with
      histological cirrhosis only (P < 0.01). CONCLUSIONS: Injecting drug use is the
      major risk factor for chronic HCV infection in Australia. In patients with an
      identifiable risk factor, the most significant factor associated with a biopsy
      finding of cirrhosis is the time since first exposure to HCV.

PMID- 7715517
TI  - Chlamydia trachomatis conjunctivitis. Prevalence and association with genital
      tract infection.
AB  - OBJECTIVES: To determine the prevalence of Chlamydia trachomatis in acute
      conjunctivitis (non-trachoma) in Australia and to examine the source of
      transmission. DESIGN: A prospective survey of 400 consecutive patients presenting
      with acute conjunctivitis to the Royal Victorian Eye and Ear Hospital Emergency
      Department, Melbourne, from May to November 1991. Patients identified with
      chlamydial conjunctivitis during the survey period and in the following two
      months were assessed for concomitant genital infection. RESULTS: Chlamydia was
      the causative organism in 2% of patients with acute conjunctivitis. Of 15
      patients with chlamydial conjunctivitis, 11 presented with disease in one eye
      only, and the same number had had symptoms for longer than two weeks. Many had
      been seen previously by experienced ophthalmologists, yet there were long delays
      in making a definitive diagnosis. Ten of the 12 adult patients who were assessed
      had signs of concomitant genital tract infection, although none had past or
      current genital tract symptoms. Serotyping of chlamydial isolates from the
      genital tract and eye showed concordance in individual patients. CONCLUSION: Most
      cases of ocular chlamydia infection have a genital source. Therefore, it is
      essential that all patients with chlamydial conjunctivitis and their sexual
      partners are examined and treated for concomitant genital infection.

PMID- 7715516
TI  - The comprehensibility of Australian educational literature for patients with
      asthma.
AB  - BACKGROUND: Education of patients with asthma is aimed at improving their
      knowledge, skills and attitudes, and thus compliance and control. Patient
      information pamphlets play a role in education, medication information and
      informed consent processes, and must be understood. We assessed the
      comprehensibility of Australian pamphlets on asthma. METHOD: 50 Australian
      pamphlets on asthma (written in English for adults) were selected from the Asthma
      Foundation, a teaching hospital in South Australia, the pharmaceutical industry,
      the National Asthma Campaign and specialist books and journal articles. The
      Australian Rix readability formula was used to estimate the grade of reading
      difficulty, and thus comprehensibility, of these patient information pamphlets
      (grade 1 = most comprehensible; grade 12 = most difficult). RESULTS: The mean
      grade of reading difficulty of the 50 patient information pamphlets was 8 (SD,
      1.4; range, 6-11). One-third were written at or above grade 9 and two-thirds were
      at or above grade 8. CONCLUSION: As recent educational attainment data suggest
      that up to 52% of 15-69-year-olds in Australia comprehend text at or below grade
      7, a substantial number of pamphlets on asthma are beyond the reading and
      comprehension abilities of many of their target population.

PMID- 7715518
TI  - How general practitioners store vaccines. A survey in south-western Sydney.
AB  - OBJECTIVE: To describe how general practitioners store vaccines. DESIGN: A cross
      sectional descriptive survey of general practices and observation of storage
      procedures for vaccines. SETTING: South-western Sydney between September and
      December 1993. PARTICIPANTS: 232 randomly selected general practitioners working
      in south-western Sydney, of whom 76% responded to a questionnaire. Vaccine
      storage was observed in 20 general practices. RESULTS: At 80% of practices, one
      person was responsible for vaccine storage. Only 30% of respondents used a
      vaccine-only refrigerator. Only 16% of respondents had a means of measuring
      temperature, while 5% kept a record of refrigerator temperature. Of the general
      practices that were monitored, the measured temperature of 70% of the
      refrigerators used for storing vaccines was within the recommended range of 2
      degrees C-8 degrees C. CONCLUSIONS: Vaccine storage would improve in general
      practices in south-western Sydney if vaccine-only refrigerators were used and
      temperature was monitored with maximum-minimum thermometers.

PMID- 7715519
TI  - The Diabetes Control and Complications Trial. Implications for children and
      adolescents. Australasian Paediatric Endocrine Group.

PMID- 7715520
TI  - Necrotising arachnidism treated with hyperbaric oxygen.

PMID- 7715521
TI  - Assaulted.

PMID- 7715522
TI  - The patenting of medical treatment.
AB  - The Full Federal Court of Australia recently held, in a decisive break with long
      established legal principle, that methods of medical treatment are patentable
      inventions. The judgment signals the advent of monopolies and therefore monopoly
      prices on new therapeutic procedures until now made freely available to the
      medical profession. It also heralds delays in the dissemination of information
      about discoveries of such procedures through teaching and publication until a
      patent application can be prepared for and made.

PMID- 7715523
TI  - Scanless diagnosis of a lumbar disc protrusion.

PMID- 7715524
TI  - The origins of cerebral palsy: a consensus statement.

PMID- 7715525
TI  - Divisions of general practice: too much too quickly.

PMID- 7715526
TI  - Divisions of general practice: too much too quickly.

PMID- 7715527
TI  - Divisions of general practice: too much too quickly.

PMID- 7715528
TI  - Improving diagnosis of Huntington's disease by analysis of an intragenic
      trinucleotide repeat expansion.

PMID- 7715530
TI  - Poor correlation between density of malaria parasitaemia and clinical symptoms in
      the Solomon Islands.

PMID- 7715529
TI  - Upper gastrointestinal tract.

PMID- 7715531
TI  - Migraine precipitated by adenosine.

PMID- 7715532
TI  - Frequency of coumarin hepatotoxicity.

PMID- 7715533
TI  - Free-flow waterbeds are potentially deadly to infants.

PMID- 7715534
TI  - Doctors, research funds and marketing.

PMID- 7715535
TI  - Drugs for epilepsy.

PMID- 7715536
TI  - Molecular characterization of the cfb gene encoding group B streptococcal CAMP
      factor.
AB  - An internal fragment of the cfb gene from group B streptococcal (GBS) strain R268
      was amplified by polymerase chain reaction (PCR) using degenerate primers with
      sequences derived from the CAMP-factor amino acid (aa) sequence of GBS strain
      NCTC8181 [Ruhlmann et al. (1988) FEBS Lett 235:262-266]. After cloning and
      sequencing this fragment, the remainder of cfb and the adjacent 5' and 3'
      sequences were amplified by inverted PCR of genomic DNA and directly sequenced
      from the PCR product. Within the 1560 bp sequenced, a complete cfb gene deviating
      in two deduced aa residues from the published sequence was identified. In
      addition, the cfbR268 sequence contained a 29-aa leader peptide. Using primers
      directed to the 5' and 3' ends of cfb for PCR, a cfb gene of uniform size could
      be detected in 19 clinical GBS isolates including three phenotypically CAMP
      negative strains. Utilizing Northern blot analysis and primer extension assays,
      the cfbR268 promoter was located and the length of the cfb transcript was
      assessed at about 1100 bp. In a parallel experiment, no cfb transcript could be
      detected from the CAMP-negative GBS strain 74-360. The complete cfbR268 gene and
      different portions of its 5' and 3' ends were cloned into the plasmid pJLA602 and
      expressed in E. coli DH5 alpha. The recombinant peptides could be detected by
      Western immunoblots with polyclonal antiserum. Only the full-sized recombinant
      CAMP-factor was found to exert co-hemolytic activity in a sheep-blood agar assay.
      This co-hemolytic activity could be inhibited by anti-CAMP antiserum.

PMID- 7715537
TI  - Major histocompatibility complex class II binding site for streptococcal
      pyrogenic (erythrogenic) toxin A.
AB  - Streptococcal pyrogenic exotoxin A (SPEA) is an important pathogenicity factor of
      group A streptococci. It is a member of the family of "superantigens" produced by
      Staphylococcus aureus and Streptococcus pyogenes and its T lymphocyte stimulating
      activity is involved into the pathogenesis of certain diseases caused by pyogenic
      streptococci. In this study we have produced and characterized recombinant SPEA
      molecules in Escherichia coli. These molecules are indistinguishable from natural
      SPEA in both T cell stimulatory and HLA class II binding activities. Human class
      II molecules are more efficient than mouse class II molecules in presenting SPEA
      to T cells. In binding tests to major histocompatibility complex class II
      positive cells SPEA competes with staphylococcal enterotoxin B and A but not with
      toxic shock syndrome toxin-1.

PMID- 7715538
TI  - Protection of mice against an influenza virus infection by oral vaccination with
      viral nucleoprotein incorporated into immunostimulating complexes.
AB  - Influenza A virus nucleoprotein (NP) was integrated into immunostimulating
      complexes (ISCOMs) after attachment of bacterial lipopolysaccharide to the
      antigen. Oral immunization with these NP-ISCOMs protected mice fully against an
      otherwise lethal challenge infection with an unrelated influenza virus subtype
      without the appearance of severe clinical signs or extensive pathological lesions
      in the lungs. Mice immunized with analogous bovine serum albumine-incorporated
      ISCOMs all died. After oral immunization, high titers of NP-specific antibodies,
      particularly IgA, could be detected in the bronchoalveolar fluid and in the blood
      serum. No cytotoxic lymphocytes could be demonstrated in the spleens or the lungs
      of vaccinated mice, and no anti-NP antibody-dependent cytolysis of infected host
      cells was mediated by complement or in the form of an antibody-dependent cell
      cytotoxicity. However, a vigorous delayed-type hypersensitivity reaction was
      produced after probing vaccinated animals with purified NP. No comparable
      protective immunity or antibody response was induced by a strictly intragastric
      administration of NP-ISCOMs. It appears, therefore, that the general and local
      immune response in the lungs was primarily stimulated through contact of NP
      ISCOMs with the mucous membrane of the oro-pharyngeal cavity and that cytotoxic
      effects did not play a major role for the establishment of the protective
      immunity. Partial protection against a lethal challenge was observed in chickens
      immunized with NP-ISCOMs in the drinking water.

PMID- 7715539
TI  - Incidence of bone marrow involvement in Ewing's sarcoma: value of extensive
      investigation of the bone marrow.
AB  - PURPOSE: Bone marrow (BM) status is a critical matter when intensified
      chemotherapy with bone marrow rescue is proposed to improve the survival of
      patients with poor prognosis Ewing's sarcoma (ES): metastatic or relapsing
      disease. A systematic bone marrow investigation was performed in all the patients
      with newly diagnosed ES or relapsing ES to assess their BM status. PATIENTS AND
      METHODS: From January 1985 to February 1989, 59 untreated patients and five
      patients at the time of relapse had a bone marrow investigation under general
      anesthesia: two BM biopsies and two BM aspirates until May 1986, then two BM
      biopsies and 10 BM aspirates. The classical method of smearing each BM aspirate
      was compared to cytocentrifugation of the pool of BM samples after gradient
      density separation. RESULTS: The BM was involved in 13 of 59 untreated patients.
      BM was the single site of metastatic spread in only one patient but was involved
      in 52% of the patients with metastatic disease at other sites. This involvement
      was focal in several patients and frequent discrepancies were noted between the
      aspirates and biopsies at the various sites explored. The number of positive
      cases of BM involvement discovered by the two methods is somewhat limited.
      However preliminary results indicate a superior rate of positive smears with the
      pool technique which did however fail to detect involvement in some cases.
      CONCLUSIONS: The present study indicates that 1) BM involvement is a frequent
      event in metastatic ES (52%); 2) is often multifocal and therefore requires
      extensive BM investigation; and 3) further investigation of the pool technique to
      facilitate the BM screening is warranted.

PMID- 7715540
TI  - Male gonadal function after chemotherapy in survivors of childhood malignancy.
AB  - Investigations of adult patients have shown that chemotherapy causes gonadal
      damage, but much less information is available about the impact of chemotherapy
      on gonadal function in children with malignant disease. At one time, being
      prepubertal during therapy was thought to confer some protection against
      chemotherapy induced gonadal damage. However, recent studies have indicated
      otherwise. We designed this study to assess gonadal function in 15 postpubertal
      males who had received polychemotherapy for a malignant disease during childhood
      and we compared them with 13 control adults males. The mean age of the patients
      at the time of the study was 18.2 +/- 3.6 years (range 13.8-29.0), and when given
      chemotherapy treatment was 10.2 +/- 3.0 years (range 6-16). At that time 12 were
      prepubertal and at the time of the study all were Tanner V. The mean interval
      from the completion of treatment until the study was 6.42 years (range 2.0-16.5).
      All patients had received polychemotherapy. We evaluated testicular size, sperm
      counts, LH and FSH after GnRH test, and testosterone levels. Puberty had
      progressed normally in all patients. We found no significant differences in
      testosterone and basal LH levels between patients and controls. However, we
      detected an appreciable difference in peak LH levels (P < 0.05) and in basal and
      peak FSH levels (P < 0.001). Seven patients had exaggerated LH response to GnRH,
      indicating dysfunction of the Leydig cells. The results of semen analyses were: 8
      patients had azoospermia, 3 oligospermia, and 1 patient had a normal semen
      analysis. All patients with semen abnormalities presented a basal and peak FSH
      higher than the mean +2 SD of the control group. In summary, we found no evidence
      of gonadal protection in prepubertal patients. We found a high incidence of
      germinal cell damage, whereas Leydig cell abnormalities were found less often. An
      endocrine study of patients that have received chemotherapy is warranted.

PMID- 7715541
TI  - Cardiac failure and dysrhythmias 6-19 years after anthracycline therapy: a series
      of 15 patients.
AB  - The clinical course of late symptomatic anthracycline cardiomyopathy, and
      resultant changes of cardiac function, were described in 15 patients. They
      represented a subset of 300 patients who had cardiac evaluations to identify the
      prevalence of late cardiotoxicity more than 4 years after anthracycline therapy
      in these patients. The clinical course and all available cardiac evaluations
      including electrocardiography, continuous taped electrocardiography,
      echocardiography, radionuclide cardiac angiography, cardiac catheterization, and
      endomyocardial biopsy, of the 15 patients were reviewed. The patients had
      received 285-870 (median 540) mg/M2 of daunorubicin and/or doxorubicin 6-19
      (median 12) years prior to the onset of late symptoms. Seven patients also had
      2,100-4,000 cGy mediastinal radiotherapy. Five patients had required treatment
      for cardiac symptoms at the end of chemotherapy but 10 patients had no cardiac
      problems anteceding their late decompensation. Fractional shortening on
      echocardiogram at late decompensation was 8-20% (median 17%) and radionuclide
      left ventricular ejection fraction was 8-59% (median 38%). All were treated with
      digitalis and diuretics and 13/15 with afterload reduction, with at least
      transient improvement of symptoms. They were followed for 1-9 (median 3) years
      after late decompensation. One died of uncontrollable cardiac failure. Another
      underwent successful cardiac transplantation. Conduction abnormalities and
      dysrhythmias were present in 14/15 patients and 3 died suddenly. Two more had
      syncope, one requiring an automatic cardiac defibrillator. Endomyocardial biopsy
      or autopsy revealed hypertrophy and fibrosis in 10/10 patients. Our patients with
      early cardiac symptoms improved transiently but decompensated later and patients
      with no early symptoms developed cardiac symptoms more than 10 years after
      anthracycline therapy. Therefore, patients who have received anthracyclines
      should have continued cardiac evaluation.

PMID- 7715542
TI  - Safety and efficacy of l-leucovorin rescue following high-dose methotrexate for
      osteosarcoma.
AB  - High-dose methotrexate with leucovorin rescue (HDMTX-LCV) is an important
      component of regimens used in the treatment of osteosarcoma. As of this writing
      the commercially available form of leucovorin is a racemic mixture of d- and l
      diastereoisomers; the l-isomer is the active component. This study describes the
      efficacy and safety of l-leucovorin in HDMTX-LCV regimens. Fifteen patients with
      osteosarcoma who were enrolled into or treated according to Pediatric Oncology
      Group protocols 8759 and 8651 received l-leucovorin (7.5 mg every 6 hours) in
      place of d,l-leucovorin following high-dose methotrexate. Safety data were
      collected for 1 week after each course or until any toxicities resolved. The mean
      number of l-leucovorin doses per course was 16.2 and the mean total dose per
      course was 126 mg. Adverse experiences were generally mild or moderate and
      occurred in 54 (60%) of 90 courses of l-leucovorin therapy. One l-leucovorin
      patients, who had inadequate methotrexate rescue, developed severe typhlitis.
      There were no instances of severe, acute methotrexate toxicity. Myelosuppression
      was seen but, in general, was not severe. These results support the conclusion
      that l-leucovorin effectively rescues patients from the toxicity of high-dose
      methotrexate.

PMID- 7715543
TI  - Recovery of natural killer cells after chemotherapy for childhood acute
      lymphoblastic leukemia and solid tumors.
AB  - Recovery of natural killer (NK) cells after cessation of chemotherapy for
      childhood acute lymphoblastic leukemia (ALL) and solid tumors was investigated in
      25 children aged 3 to 18 years. The numbers of CD3-CD56+, CD16+, and CD8-CD57+
      cells in peripheral blood were analyzed with monoclonal antibodies and flow
      cytometry at 0, 1, 3, 6, 9, and 12 months after discontinuation of therapy. The
      CD3-CD56+ and CD16+ cell counts of ALL patients (n = 14) were below the mean -1
      SD values of controls at cessation but normalized within one month due to a rapid
      2.1 and 4.5 fold increase, respectively. The CD8-CD57+ cell count of ALL patients
      was normal compared to controls at cessation. In solid tumor patients (n = 11),
      the counts of all NK cell phenotypes studied were of normal amount compared to
      controls at cessation and no vigorous increase occurred after the therapy. NK
      cell function was determined by killing K 562 target cells in five patients. In
      the two standard risk ALL patients tested, the activity was still low at 5 months
      after therapy. In contrast, the function was normal at 1 month (Wilms' tumor), 3
      months (Mb Hodgkin's) and 6 months (Burkitt lymphoma). In conclusion, NK cell
      counts were decreased compared to controls during therapy for ALL, but recovered
      rapidly afterwards. In spite of normal counts, NK cell function may be impaired
      for several months. The number and function of NK cells is less affected in solid
      tumor patients. These differences may reflect the milder immunosuppressive effect
      of interval cytostatic medication in solid tumor patients when compared to the
      more intensive continuous therapy in ALL patients.

PMID- 7715544
TI  - Brainstem neoplasms.

PMID- 7715545
TI  - Neuroblastoma IV-S followed by extra-adrenal pheochromocytoma 15 years later.
AB  - Common origin of sympathoblasts and pheochromoblasts from the neural crest cells
      is generally accepted. Neuroblastoma and pheochromocytoma result from an abnormal
      proliferation of these committed cells. They are included in the group of
      neuroendocrine neoplasms, formerly named Apudomas. Previous reports of mixed
      tumours of neuroblastoma and pheochromocytoma, and ganglioneuroma and
      pheochromocytoma, support this hypothesis. A case of extra-adrenal
      pheochromocytoma in an adolescent who 15 years before was successfully treated
      for a stage IV-S neuroblastoma without evidence of primitive tumour is reported.
      Two hypothesis are formulated: (1) the second neoplasm may have arisen from the
      unlocated primitive tumour, probably silent evolution could be due to its
      maturation into ganglioneuroma-pheochromocytoma; (2) taken into account a common
      origin of both neoplasms, the patient may have a genetic predisposition to
      develop neuroendocrine tumours. Whatever the mechanism, second neoplasms, as the
      case reported, late relapses, and late toxic effects may justify long follow-up
      of neuroblastoma survivors.

PMID- 7715546
TI  - Secretion of a large molecular-weight form of insulin-like growth factor by a
      primary renal tumor.
AB  - A 5-year-old boy with an abdominal mass was found to have a primary renal tumor
      of poorly identifiable histology. Prior to resection of the tumor, the patient
      exhibited several episodes of biochemical hypoglycemia. The hypoglycemia did not
      recur after operation. Analysis of tumor tissue and of pre- and post-operative
      sera by column chromatography showed elevated insulin-like growth factor II (IGF
      II) levels in the tumor; an abnormal large-molecular weight precursor form of IGF
      II (pro-IGF-II) comprised 53% of total IGF-II in the tumor and 42% in
      preoperative serum. No pro-IGF-II was found in the serum 6 weeks post
      operatively. Abnormal IGF-II secreted by the tumor may have mediated the
      hypoglycemia seen prior to tumor resection. This pediatric renal tumor is the
      first to our knowledge for which an association of non-islet cell tumor-related
      hypoglycemia and elevated tumor IGF-II content has been described.

PMID- 7715547
TI  - [The clinico-pathogenetic characteristics of gastric and duodenal peptic ulcer
      when combined with opisthorchiasis].

PMID- 7715548
TI  - [Changes in the bactericidal activity of the cementing fraction in ixodid tick
      saliva under the influence of the presence of the tick-borne encephalitis virus].
AB  - It is demonstrated that the abundance of bactericidal compounds in the salivary
      cement plug of ixodid ticks is changing under the influence of virulent tick
      borne encephalitis virus (TBEV) reproduction in their bodies. TBEV infected
      Ixodes persulcatus cement plug-forming lytic zone size enlarged in comparison
      with the naive tick one whereas Micrococcus lysodeikticus lytic zones induced by
      the cement plug of TBEV infected Amblyomma hebraeum nymphs or Rhipicephalus
      appendiculatus females reduced compared with produced by noninfected specimens.
      It is supposed that increasing of the lysozyme that production by the main TBEV
      vectors (Ixodinae ticks) infected salivary gland cells in comparison with
      suppression of the bactericidal qualities of saliva of the ticks which are not
      TBEV vectors in the nature (Amblyomminae ticks) is one of markers of the
      specificity of I. persulcatus-TBE virus interface.

PMID- 7715549
TI  - [The isolation and immunochemical study of Leishmania antigens].
AB  - The authors describe a procedure for producing the antigen by using a
      promastigotic suspension of the high-virulent inoculative strain Leishmania
      major. A Leishmania culture medium was improved to enhance the yield of parasites
      up to 1-3 billion cells in a flask. The grown culture was washed off with
      isotonic sodium chloride solution, from the medium residues and concentrated up
      to 1 billion cells per ml of the cvolume. The cell concentrate contained no
      rabbit blood additive, as evidenced by the gel double diffusion test. The
      combinations of destruction via multiple freezing-unfreezing or lyophilization,
      followed by ultrasound treatment were found to be the best modes of promastigotic
      disintegration. The antigenic suspension generally displayed 3-5 precipitation
      lines with hyperimmune rabbit sera and 1-3 precipitation lines with sera from the
      infected animals. The number of precipitation lines is higher in the suspension
      from the high-virulent Leishmania strains. Fractions of protective antigens have
      not been detected so far.

PMID- 7715551
TI  - [The biology of Paragonimus westermani ichunensis in the Maritime Territory.
      Experimental research].
AB  - It has been experimentally found that larval and pulmonary paragonimiasis types
      are caused by the trematode Paragonimus westermani ichunensis. The development of
      either paragonimiasis in nontypical definitive hosts depends on the stage of
      larval development when they penetrate into the mammal. Only the P. westermani
      ichunensis trematode is likely to develop with the participation of Juga mollusks
      on the territory of the Primorye.

PMID- 7715550
TI  - [Tertian P. vivax malaria in West Africa].

PMID- 7715552
TI  - [The role of opportunistic protozoa in human pathology today].
AB  - The paper deals with opportunistic protozoa, their common properties distinctions
      from commensals and obligate parasites, and the specific features of their caused
      opportunistic infections. It also provides evidence for the increasing
      contribution of opportunistic protozoa to human pathology today and for paramount
      necessity for researchers and practitioners of various disciplines to lay a
      special emphasis on them.

PMID- 7715553
TI  - [The effect of iuvemon on oogenesis in female Anopheles sacharovi Favre
      mosquitoes and their infection with the malarial causative agent Plasmodium
      gallinaceum Brumpt].
AB  - The paper provides evidence that the An. sacharovi females which do not develop
      mature eggs after blood-sucking on the malaria-infected donor could not be
      infected by the bird malaria agent P. gallinaceum. The addition of juvemon (an
      analogue of juvenile hormone) to glucose solution (mosquito carbohydrate diet)
      before blood meal stimulates the vitellogenesis of the mosquito after blood
      digestion, as clearly demonstrated on the female with an incomplete portion of
      the infected blood. This study has demonstrated that the juvemon does not exert a
      direct effect on mosquito susceptibility to the bird malaria agent, but it
      increases the number of females with mature eggs, thus promoting the increase in
      the percentage of the infected specimens and the number of oocysts.

PMID- 7715554
TI  - [Approaches to assessing the parasitological profile of Russia. 1. Study of the
      method of quantifying].
AB  - The technique may be effectively used in assessing the territory of the Russian
      Federation for human parasitic diseases (some parasitic entities, their
      complexes, economic damage caused by parasitoses, etc.) on the basis of official
      statistics. The aggregability levels will greatly vary with the nature of the
      baseline values while cartographically describing the parasitism situation in an
      area. The best results are obtained while estimating the absolute number of the
      notified parasitic cases, rather the morbidity rates calculated per 100,00
      population. The areas including 2 first quartiles (i.e. the most high density)
      concomitantly for 6, 5, 4, etc. parasitoses while assessing the parasitic
      situation. The areas where the parasitic diseases under study are recorded, but
      which have no infestation rates that form the first 2 quartiles (i.e. that are
      characterized by a comparatively low density for the whole analyzed parasitic
      complex) remain burden-free.

PMID- 7715555
TI  - [The typology of natural foci of tick-borne rickettsiosis].
AB  - The authors have developed a typological classification of tick-borne
      rickettsiosis foci by the type of the main carrier by identifying 6 major types
      out of which the Dermacentor steppe and partially wooded steppe foci are most
      extensive and epidemiologically significant. They provide a spatial and
      functional characterization of the foci of this infection within the currently
      known Rickettsia sibirica area, which is applicable to make epidemiological
      predictions and differential preventive measures.

PMID- 7715556
TI  - [Small mammals in the natural foci of tick-borne encephalitis in central Siberia.
      1. The extent of the immune stratification to the causative agent of the
      infection among Insectivora and rodents].

PMID- 7715557
TI  - [An attempt at an economic assessment of the damage caused by allergenic house
      dust mites].
AB  - Mites have been found to contribute to the etiology of some allergic diseases
      most common in Uzbekistan. The economic losses caused by atopic dust-borne asthma
      have been estimated. The losses due to damage to the national income, which are
      done by disability and to the direct and indirect expenses on treatment and
      disability allowance have been calculated and compared. Such an attempt is useful
      to calculate the profitability of prevention of domestic dust mite-caused
      diseases and of the mite control measures.

PMID- 7715558
TI  - [A comparative study of the efficacy of medamine, albendazole and embovin in
      models of syphaciasis and aspiculariasis].
AB  - The study covers the study of three antinematodal agents: the original national
      drug medamine with albendazole and embovin (pyrathel pamoate), which have been
      reproduced at the E. I. Martsinovskii Institute of Medical Parasitology and
      Tropical Medicine, with murine Syphacia obvelata and Aspiculuris tetraptera
      infection models. The quantitative parameters of the anthelmintic action of
      medamine, albendazole and embivin were comparatively defined for the first time.

PMID- 7715559
TI  - [Pathology of pregnancy and the fetus in Lyme disease].

PMID- 7715560
TI  - [The specific and biological action of chemical preparations and their
      combination with pathogenetic agents in trichinosis].
AB  - The hypersensitizing effect of benzimidazole carbamates (BC), the therapy for
      trichinellosis, especially in heavily infected patients, determines the necessity
      of simultaneous administration of glucocorticoids (GC) for the prevention of
      severe systemic and organ-specific complications. This combination delayed the
      convalescent period, in severe cases it provokes coagulopathic disorders,
      infrequently fatal haemorrhages. The combination of BC with nonsteroidal anti
      inflammatory drugs (NSAIDs) significantly shortened the convalescent period in
      semisevere and moderate cases of the disease along with normalized PGF and PGE
      production. In experimental mice and guinea pigs, the inhibition of specific T
      cell responses without inhibiting their response to FGA, and the high antibody
      mediated cytotoxic activity after BC and NSAID therapy were found. Thus, in
      severe cases of the disease GC should be applied very immediately, replaced later
      by NSAIDs. The possible role of the biological action of BC, as donors of
      imidazoles in the microenvironment of muscle larvae, favoured by the poor content
      of natural imidazoles is discussed.

PMID- 7715561
TI  - The development of PdNi thermoseeds for interstitial hyperthermia.
AB  - Magnetic induction heating of thermoseed implants can be used to produce highly
      localized hyperthermia in deep-seated tumors. Automatic temperature control
      throughout the tumor can be achieved by the self-regulating character of
      ferromagnetic seeds, which corrects for local variations in heat loss due to
      blood perfusion. An increased sharpness of the ferromagnetic transition at the
      Curie temperature, Tc, improves the performance of self-regulating control. This
      was realized for palladium-nickel alloys by a "cold working" procedure preceded
      and followed by annealing. Palladium-nickel seeds with a predetermined Tc were
      produced, showing a sharp decrease at Tc of the magnetic susceptibility and the
      heat production.

PMID- 7715562
TI  - Investigations of large vessel cooling during interstitial laser heating.
AB  - Interstitial laser heating of tissues is influenced by blood flow in the
      treatment region. Temperature gradients around large blood vessels may result in
      local underheating of tissues. A three-dimensional, time-dependent finite
      difference model of interstitial laser heating around large vessels is presented.
      A thermal conduction model was developed using a transport theory approximation
      for the energy distribution from an optical line source. Calculated transient
      temperature profiles and temperature reductions around 0.144 and 0.400 cm diam
      vessels show qualitative agreement with those measured in a series of tissue
      phantom studies. Experiments and calculations for a large vessel located
      approximately 1.0 cm from the optical source indicate that temperature reductions
      are less than 1 degree C at distances greater than approximately 1.0 cm from the
      vessel surface. The model also indicates that significant reductions in the
      extent of a thermal coagulation boundary can occur if a large vessel is situated
      inside the normal coagulation zone.

PMID- 7715564
TI  - General ion recombination for ionization chambers used under irradiation
      conditions relevant for diagnostic radiology.
AB  - General ion recombination has been studied under irradiation conditions relevant
      for diagnostic radiology and with four different ionization chambers. When the
      exposure time is appreciably shorter than the ion transit time, the exposure can
      be designated as pulsed irradiation. On the contrary, for relatively long
      irradiation times, the term continuous irradiation can be applied. Recombination
      was estimated by measuring the collected charge at various collecting potentials
      of the ionization chamber. This is a well-known method in radiotherapy, but
      unfortunately it cannot be used in diagnostic radiology with typical exposure
      meters, since they do not offer the option of varying the collecting potential.
      For exposures with diagnostic x-ray units, an alternative approach is to vary the
      exposure or exposure rate over a wide range at a constant collecting potential.
      Experimental and theoretical estimates of ion recombination did not yield similar
      values. This might be due to several causes, such as differences between the
      actual and the nominal dimensions and volumes of the ionization chambers, due to
      errors and uncertainties in the physical parameters used in the theoretical
      models or due to deviations of the shape of the ionization chambers from the
      perfect cylindrical or parallel plate geometry. For better accuracy, corrections
      for recombination losses should therefore be based on experimental verification
      rather than on theoretical models.

PMID- 7715563
TI  - A verification of the Monte Carlo code MCNP for thick target bremsstrahlung
      calculations.
AB  - The bremsstrahlung spectra from thick targets of Be, Al, and Pb are calculated
      using the Monte Carlo code MCNP (Monte Carlo N-particle). The current version of
      MCNP (v.4A) incorporates a coupled electron-photon transport scheme that allows
      the user to estimate the photon fluence produced from primary electron
      interactions. The simulation parameters are based on bremsstrahlung measurements
      of 15 MeV electrons incident on thick targets of Be, Al, and Pb at various angles
      between 0 degree and 90 degrees. The integrated yield and mean energy of each
      bremsstrahlung spectrum is calculated for the three targets at these angles. For
      angles less than 60 degrees the integrated yield calculated by MCNP4A is within
      6% of measured values for the three targets. Furthermore, predicted mean energy
      is within 7% of the values derived from measurement for all angles tested. Also
      compared are the performances of two MCNP4A fluence tallies; a next-event
      estimator (detector tally) and a track length estimator (cell tally). Timing
      studies indicate the detector tally will perform the integrated yield
      calculations to a precision of 1% approximately 10 to 50 times faster than the
      conventional cell tally for an emission angle of 0 degree.

PMID- 7715565
TI  - Evaluation of kerma ratios in a p(66)/Be(40) neutron therapy beam.

PMID- 7715566
TI  - A computational model for electron backscattering in electron dosimetry.
AB  - A one-dimensional electron transport algorithm based on the ideas of invariant
      imbedding has been developed and applied to the problem of electron
      backscattering in electron dosimetry. Results have been compared with
      experimental and Monte Carlo results. Agreement appears to be reasonable at low
      incident energies (0.5 to 10 MeV) and low Z(Z < or = 65) materials.

PMID- 7715567
TI  - Reconstruction of 12 MV bremsstrahlung spectra from measured transmission data by
      direct resolution of the numeric system AF = T.
AB  - An investigation of x-ray spectral reconstruction from transmission data by
      direct resolution of the matrix system A*F = T (using spectral algebra formalism)
      has been previously presented. The resolution has been done with simulated
      spectrum. In this paper, the method on a real case of a 12 MV photon beam was
      tested. A special study of the setup has been made to estimate and reduce the
      experimental errors that could alter the results. In order to convert F(E) (a
      fraction of the signal due to a photon of energy E) into photon fluence phi (E),
      the chamber energy response R(E) has been studied and an approximated analytical
      function for its representation was proposed. Spectra reconstructed from
      different transmission data using different attenuators, buildup caps, and
      ionization chambers have been compared to verify the uniqueness of the
      reconstructed spectra. To test the validity of the results, dosimetric values,
      such as Depth Dose Data have been calculated, from our spectrum, using a specific
      code developed by Kosunen et al. The results show a good agreement between the
      measured and calculated data.

PMID- 7715568
TI  - Radiological properties of a prototype multi-rod collimator for producing
      irregular fields in photon radiation therapy.
AB  - A prototype multi-rod collimator for producing irregular fields in photon
      radiation therapy has been designed and built. The mechanical details of the
      design and operation of the multi-rod collimator are discussed. Beam profiles for
      an approximately 10 x 10 cm2 field have been measured at various depths in
      phantom, and compared with profiles obtained using the secondary collimator jaws
      alone and with cast metal blocks. The ability of the collimator to produce
      irregular fields is demonstrated with reference to some commonly encountered
      therapy fields and the ability to produce central blocks and island blocks is
      discussed. Isodose curves for selected irregular fields are presented.

PMID- 7715569
TI  - The 200-MeV proton therapy project at the Paul Scherrer Institute: conceptual
      design and practical realization.
AB  - The new proton therapy facility is being assembled at the Paul Scherrer Institute
      (PSI). The beam delivered by the PSI sector cyclotron can be split and brought
      into a new hall where it is degraded from 590 MeV down to an energy in the range
      of 85-270 MeV. A new beam line following the degrader is used to clean the low
      energetic beam in phase space and momentum band. The analyzed beam is then
      injected into a compact isocentric gantry, where it is applied to the patient
      using a new dynamic treatment modality, the so-called spot-scanning technique.
      This technique will permit full three-dimensional conformation of the dose to the
      target volume to be realized in a routine way without the need for individualized
      patient hardware like collimators and compensators. By combining the scanning of
      the focused pencil beam within the beam optics of the gantry and by mounting the
      patient table eccentrically on the gantry, the diameter of the rotating structure
      has been reduced to only 4 m. In the article the degrees of freedom available on
      the gantry to apply the beam to the patient (with two rotations for head
      treatments) are also discussed. The devices for the positioning of the patient on
      the gantry (x rays and proton radiography) and outside the treatment room (the
      patient transporter system and the modified mechanics of the computer tomograph
      unit) are briefly presented. The status of the facility and first experimental
      results are introduced for later reference.

PMID- 7715570
TI  - Calculation of monitor units for a linear accelerator with asymmetric jaws.
AB  - A simple approach was developed that calculates the output factors and tissue
      maximum ratio of an asymmetric field at any point within the open field, and
      specifically both at the central axis (when the jaws do not shadow it) and at the
      effective center of the open field, using the existing tables for symmetric
      fields and the multidepth profile information for the largest available field
      size (either open or with a wedge present). Day's method was adapted to calculate
      the effective values of the usual field-size-dependent parameters. This approach
      makes these parameters also dependent on the location of the calculation point
      relative to the field edges in an asymmetric field. This algorithm was tested by
      comparing its predictions with measurements of asymmetric and half blocked
      fields, with and without wedges, in a water phantom at different depths and off
      axis distances. The agreement between calculated and measured dose rate is within
      1%-3% even in highly asymmetric fields for both 6- and 18-MV photons.

PMID- 7715571
TI  - Fetal dose from radiotherapy with photon beams: report of AAPM Radiation Therapy
      Committee Task Group No. 36.
AB  - Approximately 4000 women per year in the United States require radiotherapy
      during pregnancy. This report presents data and techniques that allow the medical
      physicist to estimate the radiation dose the fetus will receive and to reduce
      this dose with appropriate shielding. Out-of-beam data are presented for a
      variety of photon beams, including cobalt-60 gamma rays and x rays from 4 to 18
      MV. Designs for simple and inexpensive to more complex and expensive types of
      shielding equipment are described. Clinical examples show that proper shielding
      can reduce the radiation dose to the fetus by 50%. In addition, a review of the
      biological aspects of irradiation enables estimates of the risks of lethality,
      growth retardation, mental retardation, malformation, sterility, cancer
      induction, and genetic defects to the fetus.

PMID- 7715572
TI  - Source localization for template implants with particular reference to stepping
      source afterloaders.
AB  - Source localization from radiographs can be very difficult for template-guided
      implants if the needle images overlap. At UCSF several techniques to make this
      task easier have been developed. The techniques include selection of an optimum
      simulator gantry angle, use of different types of dummies, and differential dummy
      loading. In addition, several modifications have been made in our brachytherapy
      planning computer program to facilitate source entry. As a result of these
      improvements, source localization is now accomplished in much less time with
      improved accuracy.

PMID- 7715573
TI  - Dose distributions and dose rate constants for new ytterbium-169 brachytherapy
      seeds.
AB  - Relative dose distributions in the vicinities of two new prototypes of ytterbium
      169 brachytherapy sources have been measured using lithium fluoride
      thermoluminescent dosimeters (TLD) placed in a solid water phantom. The type 6
      seed consists of four Yb2O3 spheres contained in a 0.075-mm thick titanium tube,
      with overall dimensions of 4.5 mm in length and 0.8 mm in diameter. The type 8
      seed contains a cylindrical segment of Yb wire, 2.5 mm long, sealed in a 0.075-mm
      thick titanium tube 4 mm in length and 0.5 mm in diameter. The relative dose
      distributions, measured with TLD, were compared with those predicted by Monte
      Carlo simulations (MCNP code). Experimental and theoretical dose distributions
      were generally in agreement within 5% of the local dose value. Source strength
      was determined from activity measurements using a high purity germanium (HPGe)
      spectrometer. With source strengths established, thermoluminescence was then used
      to measure the dose rate constant, lambda 0, for the type 8 seed. The measured
      lambda 0 of 1.34 +/- 0.10 cGy U-1 for the type 8 seed agrees, within statistical
      uncertainty, with the value of 1.25 +/- 0.05 cGy U-1 predicted through Monte
      Carlo simulation. Comparisons are made with experimental data reported by other
      investigators.

PMID- 7715574
TI  - A spreadsheet technique for dosimetry of transperineal prostate implants.
AB  - Although conceptually straightforward, dosimetry of permanent 125I seed prostate
      implants is not necessarily easy to implement in clinical practice, especially
      for institutions that are unwilling or unable to modify their commercial RTP
      systems. Spreadsheet techniques that aid in both preimplant treatment planning
      and post-implant dosimetric evaluation have been developed. The first spreadsheet
      converts the seed distribution expressed in terms of template grid coordinates to
      the format suitable for input into the RTP system, and determines the positions
      and loading patterns of individual needles. The second spreadsheet macroprogram
      is designed, as a modification of the Roy et al. [Int. J. Radiat. Oncol. Biol.
      Phys. 26, 163-169 (1993)] technique, to interactively determine physical seed
      locations from the post-implant CT images. Although less automated than described
      elsewhere, this approach was found acceptable for clinical practice at our
      institution.

PMID- 7715575
TI  - [The Essential Trace Element Selenium in Research and Clinical Practice.
      Proceedings of the 2nd Dresden Selenium Symposium. 2 July 1994].

PMID- 7715576
TI  - [Mechanisms of intestinal absorption of selenium].

PMID- 7715577
TI  - [Nutrition physiologic significance of the trace element selenium within the
      scope of parenteral nutrition therapy].

PMID- 7715578
TI  - [Reactive oxygen species in the pathogenesis of gastrointestinal tumors. A follow
      up study].
AB  - Development and growth of gastrointestinal tumors seems to correlate closely with
      the formation of reactive oxygen intermediates (ROI). It is known, that oxygen
      free-radicals are able to induce a precancerous stage and tumor growth by
      damaging DNA or changing the protein and lipid structure. To investigate, whether
      the cellular formation of oxygen-free radicals plays a role in the pathogenesis
      of colorectal carcinoma, we performed the study presented here. 40 patients with
      colorectal carcinoma were studied over a period of 6 months (before operation, 10
      days after operation, 3 months later, 6 months later). Oxygen-free radicals were
      determined by chemiluminescence response in the whole blood, in granulocytes and
      in monocuclear blood cells (MBC). At the same time the trace elements selenium,
      Copper and Zinc, known to play an important role as antioxidants, were measured.
      RESULTS: We observed, that the ability of granulocytes for phagocytosis was
      depleted. However, this effect could be reversed as demonstrated in in vitro
      stimulation assays. After 6 months the phagocytosis by granulocytes achieved
      again normal values. Simultaneously a dramatic increase in superoxide-anions
      generated by mononuclear blood cells was seen. This increase was still obvious
      after 6 month. Independent of the tumor state selenium deficiency was found in
      all patients. Since no substitution of selenium was performed after operation,
      this deficiency was not normalised. CONCLUSION: The ability for phagocytosis and
      therefore the immune response is reduced in a reversible manner. In addition
      reactive superoxide-anions, that are able to induce tumors, are formed. This risk
      is increased in the absence of selenium. Thus, clinical follow-up studies are
      needed to determine subclinical tumor relapses and to investigate the role of
      oxidative stress by chemi-luminescence. As consequence of this study selenium
      substitution seems to be indicated.

PMID- 7715579
TI  - [Whole blood selenium level and lipid peroxides in tumor patients treated with
      chemotherapy. DNA effects of oxygen free radicals exemplified by the NF kappa B
      transcription factor and the p53 tumor suppressor gene].

PMID- 7715580
TI  - [DNA damage to the skin caused by ultraviolet irradiation. Development,
      significance, modification].

PMID- 7715581
TI  - [Antioxidant therapy in chronic polyarthritis].

PMID- 7715582
TI  - [The role of oxygen radicals in acute pancreatitis. Clinical and experimental
      results of therapy with free radical scavengers].
AB  - Numerous studies support the theory that oxygen free radicals (OR) are involved
      in the development of tissue damage in all forms of experimental acute
      pancreatitis. OR are generated in an early phase of the disease before tissue
      damage is detectable by histology. The pathomechanism that leads to this
      oxidative stress is not fully understood. The efficacy of scavenger treatment was
      clearly proven in most models of experimental acute pancreatitis. In first
      clinical trials applying antioxidant treatment with selenium show favorable
      results in reducing the lipidperoxidation and improving the antioxidant status.
      However these preliminary results but must be supported in a larger series of
      patients to allow proper evaluation of patient outcome.

PMID- 7715583
TI  - [Decreasing mortality in acute pancreatitis with sodium selenite. Clinical
      results of 4 years antioxidant therapy].
AB  - Results obtained from pancreatitis research prove the genesis if free radicals in
      acute pancreatitis. Xenobiotics, ethanol as well as biliary diseases will induce
      a deficiency in antioxidants. In antioxidative treatment sodium selenite as a
      water soluble redox substance represented an alternative. In the middle of the
      year 1990 the therapy regime was introduced in Rostock, a short time later in
      Dresden too. The diagnosis was made by CT enhanced by a contrast medium as well
      as by clinical and paraclinical parameters. CT was repeated after a week. Up to
      May 31, 1994 there were 245 patients treated in Rostock and 85 patients in
      Dresden (n = 330). Immediately after making the diagnosis 200 micrograms were
      given as a bolus, 800 micrograms in the following 24 hours. From the second day
      on 500 micrograms of selenite were administered daily. In addition, infusions of
      carbohydrates, electrolytes (no calcium), fluid and analgetics were given.
      Lavation of the intestine was made three times daily. With a well-timed selenium
      therapy the rates of letality, complications and operation dropped drastically.
      In spite of a constant number of patients no patient has died in Rostock since
      1993, in Dresden 8 of 85 patients came ad exitum. Complications occurred if the
      therapy began too late (if patients were administered too late) and in biliary
      forms. CONCLUSION: An improvement in the prognosis of acute pancreatitis can be
      achieved if antioxidative selenium therapy with sodium selenite is introduced in
      time. In rare cases total necroses and complications in organs only occurred in
      those patients who were admitted to this therapy too late.

PMID- 7715584
TI  - [The value of selenotherapy in patients with mucoviscidosis].
AB  - In cystic fibrosis (CF) patients the antioxidative-oxidative balance is
      chronically disturbed. Free radicals were generated by bronchial-pulmonal
      infection and additional exist a deficiency of antioxidative substances by
      enteral malabsorption especially vitamin E and selenium. Because selenium is an
      essential content of glutathione peroxidase, which is acting in cytosol and cell
      membranes, for the present we tested a selenium therapy (peroral sodium selenite
      155 micrograms (Se/m2 BSA/d i. e. 4 micrograms Se/kg/d; 4 fold of recommended
      supply) in 32 CF patients. After three months of this therapy we have seen
      positive metabolic (normalized content of plasma-selenium, -glutathione
      peroxidase), endocrine (enhanced efficacy of thyroid hormones, mild increased IgF
      I reduced LDL-chol) and clinical consequences (enhanced left ventricular cardiac
      output), but in three patients side effects (anorexia, nausea, mild hair loss)
      were observed. Longtime sodium selenite therapy only with 60 micrograms Se/m2
      BSA/d over 1 year, stabilized the favourable influences without side effects. For
      CF patients therefore we recommend a sodium selenite substitution therapy, the
      best in combination with vitamin E.

PMID- 7715585
TI  - [Selenium level in patients with acute myocardial infarct and in patients with
      severe angina pectoris without myocardial infarct].
AB  - Selenium in serum and whole blood was determined in patients (n = 88) with acute
      cardiac infarction, in patients (n = 62) with severe clinical symptoms and signs
      of angina pectoris excluding cardiac infarction, and a control group (n = 62).
      The average selenium concentration of the 62 patients in the control group was
      1.00 +/- 0.17 mumol/l in the blood. The serum selenium concentration of the
      patients with cardiac infarction was significantly decreased as compared with the
      control group both on the first and tenth day (alpha = 1%) as well as after three
      months (alpha = 5%). On the twentieth day as well as six and twelve months after
      cardiac infarction no significant difference could be established. At all times
      after cardiac infarction, the blood showed a clearly decreased selenium
      concentration as compared with the control group. The difference was highly
      significant (alpha = 0.1%) on the first, tenth and twentieth day as well as after
      three and six months, and it was significant (alpha = 1%) after twelve months. On
      the first day, the average selenium concentration in the serum of the 62 patients
      with a severe attack of angina pectoris excluding acute cardiac infarction was
      0.88 +/- 0.18 mumol/l and thus highly significantly below the values for the
      control group (alpha = 0.1%). The decrease on the tenth day (0.93 +/- 0.19
      mumol/l) turned out not to be significant. The blood selenium concentration was
      highly significantly decreased on the first and tenth day (alpha = 0.1%). It was
      measured to be 1.12 +/- 0.19 mumol/l and 1.10 +/- 0.20 mumol/l
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715586
TI  - [New selenoproteins].

PMID- 7715587
TI  - [Selenium and antioxidant status in various diseases].
AB  - All healthy mammalian organisms are characterized by an equilibrium between the
      occurrence of highly reactive oxygen species and their destruction by anti
      oxidants. Numerous diseases go hand in hand with a disturbance of the
      homoeostatis. In order to avoid or minimize the destructive effect of the oxidant
      stress on biological structures, therapies utilizing drugs with anti-oxidant
      effects are increasingly being applied. Preconditions for these therapies are a
      characterisation and a follow-up of the anti-oxidant status in the diseased
      organism. In the course of the present study selenium, glutathione peroxidase and
      malondialdehyde were determined in patients with various clinical pictures
      (terminal renal insufficiency, septic shock, high-risk gravidieties,
      arterioscleroisis, pulmonary carcinoma, acute myocardial infarction, test
      patients taking the contraceptive pill). Patients with terminal renal
      insufficiency and those suffering from septic shock syndromes clearly show a
      selenium decrease in serum and whole blood as well as a drop in the GSH-Px
      activity, and increased malondialdehyde concentrations in the serum. Both are a
      reflection of an increased lipid peroxidation. First results of a selenium
      therapy are available for patients with therminal renal insufficiency and post
      traumatically induced renal failure. The interpretation of the findings in the
      categories "high-risk gravidity" and "women on the contraceptive pill", which
      show a normal GSH-Px-activity and significantly increased malondialdehyde
      concentrations, seems problematic. The organism counteracts an increased lipid
      peroxidation with a normal plasma-GSH-Px-activity, clearly a sign of a still
      normal anti-oxidant potential.

PMID- 7715588
TI  - Children at risk from ozone air pollution--United States, 1991-1993.
AB  - A national health objective for the year 2000 is to reduce exposure to air
      pollutants so that at least 85% of persons reside in counties that meet
      Environmental Protection Agency (EPA) standards (objective 11.5) (1). Ozone, the
      principle component of summer smog, is the most pervasive air pollutant in the
      United States. The risks associated with ozone and other air pollutants are
      especially increased for children and adults with asthma (2); however, children
      with no underlying pulmonary diseases also are at risk for adverse health effects
      associated with these pollutants (3). In addition, because children of
      racial/ethnic minorities are more likely to reside in areas with higher air
      pollution levels, they may be exposed to higher levels of ozone (4). This report
      presents the findings of an analysis by the American Lung Association (ALA) to
      characterize pediatric populations potentially at risk for adverse health effects
      from exposure to ozone air pollution in the United States during 1991-1993.

PMID- 7715589
TI  - Fatal and nonfatal suicide attempts among adolescents--Oregon, 1988-1993.
AB  - Suicide is the third leading cause of death among adolescents aged 15-19 years in
      the United States and second among adolescents in Oregon. During 1959-1961 and
      during 1990-1992, the rate of suicide in Oregon increased sixfold among 15-19
      year-olds. During 1988-1991, the suicide rate for adolescents in Oregon (15.5
      deaths per 100,000) was 39.6% higher than the U.S. rate (11.1). Because of the
      magnitude of this problem, in 1987 the state legislature in Oregon mandated that
      hospitals treating a child aged < or = 17 years for injuries resulting from a
      suicide attempt report the attempt to the State Health Division, Oregon
      Department of Human Resources, and that the patient be referred for counseling;
      the Oregon Adolescent Suicide Attempt Data System (ASADS) was established in
      1988. This report presents an analysis of data for adolescents aged < or = 17
      years from ASADS during 1988-1993.

PMID- 7715590
TI  - Evaluation of vaccination strategies in public clinics--Georgia, 1985-1993.
AB  - From 1987 through 1993, the vaccination coverage levels among children served in
      public health clinics in Georgia more than doubled. This increase followed the
      implementation of a multifaceted strategy that included routine measurement of
      vaccination coverage levels. This report describes this program and an analysis
      of increases in vaccination coverage during 1985-1993.

PMID- 7715591
TI  - Prevalence and impact of arthritis among women--United States, 1989-1991.
AB  - Arthritis and other rheumatic conditions are among the most prevalent chronic
      conditions in the United States, affecting approximately 38 million persons (1).
      The self-reported prevalence of arthritis is greater among women than among men,
      and for women aged > 45 years, arthritis is the leading cause of activity
      limitation (1,2). This report uses data from the National Health Interview Survey
      (NHIS) to provide estimates of the prevalence and impact of arthritis among women
      aged > or = 15 years during 1989-1991, compares the prevalence estimates of
      arthritis to other chronic conditions affecting women during 1989-1991, and
      projects the prevalence of arthritis among women in 2020.

PMID- 7715592
TI  - Trends in length of stay for hospital deliveries--United States, 1970-1992.
AB  - Obstetric delivery is the most frequent cause of hospital admission in the United
      States, reflecting the approximately 4 million births in this country each year
      (1). Because of steadily increasing hospital costs, overall lengths of hospital
      stay have declined. To assess national trends in length of stay for hospital
      deliveries, data were analyzed from CDC's National Hospital Discharge Survey
      (NHDS) from 1970 through 1992, by method of delivery. This report summarizes the
      results of the analysis.

PMID- 7715593
TI  - Deaths from melanoma--United States, 1973-1992.
AB  - Approximately three fourths of all skin cancer-associated deaths are caused by
      melanoma. During 1973-1991, the incidence of melanoma increased approximately 4%
      each year (1). In addition, the incidence of melanoma is increasing faster than
      that of any other cancer (2). To characterize the distribution of deaths from
      melanoma in the United States, CDC analyzed national mortality data for 1973
      through 1992. This report summarizes the results of that analysis.

PMID- 7715594
TI  - Reptile-associated salmonellosis--selected states, 1994-1995.
AB  - During 1994-1995, health departments in 13 states reported to CDC persons
      infected with unusual Salmonella serotypes in which the patients had direct or
      indirect contact with reptiles (i.e., lizards, snakes, or turtles). In many of
      those cases, the same serotype of Salmonella was isolated from patients and from
      reptiles with which they had had contact or a common contact. For some cases,
      infection resulted in invasive illness, such as sepsis and meningitis. This
      report summarizes clinical and epidemiologic information for six of these cases.

PMID- 7715597
TI  - Targeted mutagenesis identifies Asp-569 as a catalytically critical residue in T7
      RNA polymerase.
AB  - In order to look more closely at a well-conserved region in T7 RNA polymerase (T7
      RNAP) containing, as shown earlier, the functionally essential residues Pro-563
      and Tyr-571, we used targeted mutagenesis to change those residues within this
      region that are invariant in all single-subunit RNA polymerases, and
      characterized the mutant enzymes in vitro. The most interesting finding of this
      study was the crucial importance of the acidic group of Asp-569. In addition, we
      have shown that the phenolic ring is the most significant functional group of Tyr
      571, with the hydroxy group also contributing to promoter binding.

PMID- 7715596
TI  - Guest: a 98 bp inverted repeat transposable element in Neurospora crassa.
AB  - The region immediately 3' of histidine-3 has been cloned and sequenced from two
      laboratory strains of the ascomycete fungus Neurospora crassa; St Lawrence 74A
      and Lindegren, which have different derivations from wild collections. Amongst
      the differences distinguishing these sequences are insertions ranging in size
      from 20 to 101 bp present only in St Lawrence. The largest of these is flanked by
      a 3 bp direct repeat, has terminal inverted repeats (TIR) and shares features
      with several known transposable elements. At 98 bp, it may be the smallest
      transposable element yet found in eukaryotes. There are multiple copies of the
      TIR in the Neurospora genome, similar but not identical to the one sequenced. PCR
      amplification of Neurospora genomic DNA, using 26 bp of the TIR as a single
      primer, gave products of discrete sizes ranging from 100 bp to about 1.3 kb,
      suggesting that the element isolated (Guest) may be a deletion derivative of a
      family of larger transposable elements. Guest appears to be the first
      transposable element reported in fungi that is not a retrotransposon.

PMID- 7715595
TI  - Light-chain fibroin of Galleria mellonella L.
AB  - The posterior section of Galleria mellonella silk glands contains two abundant
      mRNAs that are identical except for the non-coding tail, which includes either
      two (1.1 kb mRNA) or three (1.2 kb mRNA) consensus sequences for polyadenylation
      sites. The transcripts are 40% homologous in the coding as well as non-coding
      regions with the mRNA encoding light-chain fibroin (L-fibroin) in Bombyx mori;
      the deduced translation product shows 43% identity with the Bombyx L-fibroin
      peptide, with all three cysteines conserved. Amino acid analysis of the N-termini
      of Galleria silk proteins revealed that L-fibroin (25 kDa) occurs in two
      isoforms, the shorter one lacking the Ala-Pro dipeptide residue at its N
      terminus. The 29 and 30 kDa Galleria silk proteins appear to be homologs of
      Bombyx silk component P25. The results suggest that evolutionary diversification
      of Galleria and Bombyx L-fibroins involves alternative polyadenylation and
      proteolytic processing sites.

PMID- 7715598
TI  - Structural analysis of Tpn1, a transposable element isolated from Japanese
      morning glory bearing variegated flowers.
AB  - The 6.4 kb transposable element Tpn1 belonging to the En/Spm family was found
      within one of the DFR (dihydroflavonol-4-reductase) genes for anthocyanin
      biosynthesis in a line of Japanese morning glory (Pharbitis nil) bearing
      variegated flowers. Sequencing of the Tpn1 element revealed that it is 6412 bp
      long and carries 28-bp perfect terminal inverted repeats. Its subterminal
      repetitive regions, believed to be the cis-acting sequences for transposition,
      show striking structural features. Twenty-two copies of the 10-bp sequence motif
      GACAACGGTT can be found as direct or inverted repeats within 650 bp of the 5' end
      of the element, and 33 copies of the sequence motif lie within 800 bp of the 3'
      terminus. All these 22 copies of the sequence motif near the 5' terminus and 30
      copies in the 3' terminal region are arranged as inverted repeats and 3-8 bp AT
      rich sequences are detected between these inverted repeats. In addition, four
      copies of 122-bp tandem repeats and six copies of 104-bp tandem repeats are
      present in the 5' and 3' subterminal repetitive regions, respectively. No large
      open reading frame characteristic of autonomous elements of the En/Spm family can
      be detected within the element. The results are discussed with respect to
      heritable changes in flower variegation in this line of Japanese morning glory.

PMID- 7715599
TI  - Cloning, nucleotide sequence, and transcriptional analysis of the nusG gene of
      Streptomyces coelicolor A3(2), which encodes a putative transcriptional
      antiterminator.
AB  - A 3 kb genomic fragment containing the nusG gene of Streptomyces coelicolor A3(2)
      was identified, cloned and sequenced. Sequence analysis revealed 3 complete and 2
      truncated open reading frames (ORFs): truncated ORFU (similar to a Bacillus gene
      encoding a thermostable aspartate aminotransferase)-secE (94 amino acids; 79.0%
      similarity to Escherichia coli SecE)-nusG (300 amino acids; 73.3% similarity to
      E. coli NusG)-rplK (144 amino acids; 88.5% similarity to E. coli ribosomal
      subunit L11)-truncated rplA (similar to E. coli ribosomal subunit L1). The gene
      organization secE-nusG-rplKA exactly matches that in E. coli. Transcriptional
      analyses by the primer extension method revealed one transcriptional start site
      each for secE and nusG, and two sites for rplK. The presence of promoters was
      also confirmed with the aid of a promoter-probe vector.

PMID- 7715600
TI  - Structure and regulation of the Erwinia carotovora subspecies carotovora SCC3193
      cellulase gene celV1 and the role of cellulase in phytopathogenicity.
AB  - The celV1 gene encoding a secreted cellulase (CelV1) of Erwinia carotovora subsp.
      carotovora SCC3193 was cloned and its nucleotide sequence determined. The gene
      contains an open reading frame of 1511 bp and codes for an exported protein of
      504 amino acids. The predicted amino acid sequence of CelV1 was highly similar to
      that of CelV of another E. c. subsp. carotovora strain SCR1193 but completely
      different from the previously characterized cellulase, CelS, of the strain
      SCC3193. Gene fusions to the lacZ reporter were employed to characterize the
      regulation of celV1 and celS. Both genes are coordinately induced in a growth
      phase-dependent manner and are catabolite repressed. Expression of celV1 but not
      celS was stimulated by plant extracts. The celS gene was expressed at a much
      lower level than celV1 under all conditions tested. Inactivation of the celV1
      gene in E. c. subsp. carotovora strain SCC3193 by marker exchange showed that
      celV1 encodes the major cellulase of strain SCC3193, as the resulting mutant
      strain SCC6001 was devoid of cellulase activity. CelV1 mutants exhibited reduced
      virulence suggesting that CelV1, although not absolutely required for
      pathogenicity, enhances the ability of strain SCC3193 to macerate plant tissue.
      Inactivation of the celS gene in the celV1 mutant did not lead to any further
      decrease in virulence.

PMID- 7715601
TI  - The cycHJKL gene cluster plays an essential role in the biogenesis of c-type
      cytochromes in Bradyrhizobium japonicum.
AB  - We present an extended genetic analysis of the previously identified cycH locus
      in Bradyrhizobium japonicum. Three new open reading frames found in an operon
      like structure immediately adjacent to the 3' end of cycH were termed cycJ, cycK
      and cycL. A deletion mutant (delta cycHJKL) and biochemical analysis of its
      phenotype showed that the genes of the cluster are essential for the biogenesis
      of cellular c-type cytochromes. Mutations in discrete regions of each of the
      genes were also constructed and shown to affect anaerobic respiration with
      nitrate and the ability to elicit an effective symbiosis with soybean, both
      phenotypes being a consequence of defects in cytochrome c formation. The CycK and
      CycL proteins share up to 53% identity in amino acid sequence with the
      Rhodobacter capsulatus Cc11 and Cc12 proteins, respectively, which have been
      shown previously to be essential for cytochrome c biogenesis, whereas cycJ codes
      for a novel protein of 169 amino acids with an M(r) of 17857. Localisation
      studies revealed that CycJ is located in the periplasmic space; it is probably
      anchored to the cytoplasmic membrane via an N-terminal hydrophobic domain. Based
      on several considerations discussed here, we suggest that the proteins encoded by
      the cycHJKL-cluster may be part of a cytochrome c-haem lyase complex whose active
      site faces the periplasm.

PMID- 7715603
TI  - The glucose repression and RAS-cAMP signal transduction pathways of Saccharomyces
      cerevisiae each affect RNA processing and the synthesis of a reporter protein.
AB  - Previously we reported that mutations in the Saccharomyces cerevisiae REG1 gene
      encoding a negative regulator of glucose-repressible genes, suppress the RNA
      processing defects and temperature-sensitive growth of rna1-1 and prp cells. This
      result and the fact that growth on non-glucose carbon sources also suppresses
      rna1-1 led us to propose that RNA processing and export of RNA from the nucleus
      are responsive to carbon source regulation. To understand how carbon source
      affects these processes, we used p70, an antigen regulated by REG1 and by glucose
      availability, as a reporter. We found that the response of p70 to glucose
      availability is mediated by both the SNF1-SSN6-dependent glucose repression and
      the RAS-cAMP pathways. These results led us to test whether the RAS-cAMP pathway
      interacts with RNA1. We found that suppression of rna1-1 appears to be mediated,
      at least in part, by the RAS-cAMP pathway.

PMID- 7715602
TI  - The cycHJKL genes of Rhizobium meliloti involved in cytochrome c biogenesis are
      required for "respiratory" nitrate reduction ex planta and for nitrogen fixation
      during symbiosis.
AB  - We report the genetic and biochemical analysis of Rhizobium meliloti mutants
      defective in symbiotic nitrogen fixation (Fix-) and "respiratory" nitrate
      reduction (Rnr-). The mutations were mapped close to the ade-1 and cys-46
      chromosomal markers and the mutated locus proved to be identical to the
      previously described fix-14 locus. By directed Tn5 mutagenesis, a 4.5 kb segment
      of the chromosome was delimited in which all mutations resulted in Rnr- and Fix-
      phenotypes. Nucleotide sequence analysis of this region revealed the presence of
      four open reading frames coding for integral membrane and membrane-anchored
      proteins. Biochemical analysis of the mutants showed that the four proteins were
      necessary for the biogenesis of all cellular c-type cytochromes. In agreement
      with the nomenclature proposed for rhizobial genes involved in the formation of c
      type cytochromes, the four genes were designated cycH, cycJ, cycK, and cycL,
      respectively. The predicted protein product of cycH exhibited a high degree of
      similarity to the Bradyrhizobium japonicum counterpart, while CycK and CycL
      shared more than 50% amino acid sequence identity with the Rhodobacter capsulatus
      Cc11 and Cc12 proteins, respectively. cycJ encodes a novel membrane anchored
      protein of 150 amino acids. We suggest that this gene cluster codes for (parts
      of) a multisubunit cytochrome c haem lyase. Moreover, our results indicate that
      in R. meliloti c-type cytochromes are required for respiratory nitrate reduction
      ex planta, as well as for symbiotic nitrogen fixation in root nodules.

PMID- 7715604
TI  - Influence of non-homology between recombining DNA sequences on double-strand
      break repair in Saccharomyces cerevisiae.
AB  - In this paper we study the influence of non-homology between plasmid and
      chromosomal DNA on the efficiency of recombinational repair of plasmid double
      strand breaks and gaps in yeast. For this purpose we used different combinations
      of plasmids and yeast strains carrying various deletions within the yeast LYS2
      gene. A 400 bp deletion in plasmid DNA had no effect on recombinational plasmid
      repair. However, a 400 bp deletion in chromosomal DNA dramatically reduced the
      efficiency of this repair mechanism, but recombinational repair of plasmids
      linearized by a double-strand break with cohesive ends still remained the
      dominant repair process. We have also studied the competition between
      recombination and ligation in the repair of linearized plasmids. Our experimental
      evidence suggests that recombinational repair is attempted but aborted if only
      one recombinogenic end with homology to chromosomal DNA is present in plasmid
      DNA. This situation results in a decreased probability of non-recombinational
      (i.e. ligation) repair of linearized plasmid DNA.

PMID- 7715605
TI  - Linear mitochondrial DNAs from yeasts: telomeres with large tandem repetitions.
AB  - The terminal structure of the linear mitochondrial DNA (mtDNA) from the yeast
      Candida parapsilosis was investigated. This mtDNA, 30 kb long, has symmetrical
      ends forming inverted terminal repeats. These repeats are made up of a variable
      number of tandemly repeating units of 738 bp each; the terminal nucleotide
      corresponds to a precise position within the last repeat unit sequence. The ends
      had an open structure accessible to enzymes, with a 5' single-stranded extension
      of about 110 nucleotides. No circular forms were detected in the DNA
      preparations. Two other unrelated species, Pichia philodendra and Candida
      salmanticensis also appear to have a linear mtDNA of similar organization. These
      linear DNAs (which we name Type 2 linear mtDNAs) are distinct from the previously
      described linear mtDNAs of yeasts whose termini are formed by a closed hairpin
      loop (Type 1 linear mtDNA). The terminal structure of C. parapsilosis mtDNA is
      reminiscent of the linear mitochondrial genomes of the ciliate Tetrahymena
      although, in the latter, the telomeric tandem repeat unit is considerably
      shorter.

PMID- 7715607
TI  - Global regulatory mechanisms affect virulence gene expression in Bordetella
      pertussis.
AB  - The influence was investigated of DNA gyrase-inhibiting drugs on the expression
      of various genes of Bordetella pertussis. We show that the promoters of the
      virulence regulatory bvg locus and of several bvg-regulated virulence factors,
      such as the fha, ptx, cya, fim2 and vrg6 loci are very sensitive to the action of
      novobiocin and coumermycin A, as reflected by transcriptional differences in gene
      expression. Inhibition of DNA gyrase by the drugs led to a strong decrease in
      transcription of these genes. Interestingly, one gene belonging to the bvg
      virulence regulon behaved differently: the promoter of the prn locus, coding for
      the outer membrane protein pertactin, involved in bacterial adhesion to
      eukaryotic cells, was induced after inhibition of DNA gyrase. The expression of
      other genes not belonging to the bvg regulon, such as those encoding porin (POR)
      and superoxide dismutase (SodB), were not, or only weakly, affected by the drugs.
      This demonstrates that with respect to drug-induced changes in DNA supercoiling
      there exist different types of promoters in B. pertussis. In an attempt to
      identify additional regulatory mechanisms that may modulate virulence gene
      expression, we investigated the effect of various environmental stimuli on the
      stability of the bvg-regulated vrg6 and the bvg-independent sodB transcripts. We
      found that some signals transduced via by the BvgS sensor protein, such as
      variations in the growth temperature or the presence of nicotinic acid, exerted a
      strong effect on the half life of these transcripts, whereas another modulating
      agent, MgSO4, did not have any influence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715606
TI  - Involvement of umuDCST genes in nitropyrene-induced -CG frameshift mutagenesis at
      the repetitive CG sequence in the hisD3052 allele of Salmonella typhimurium.
AB  - Expression of the umuDC operon is required for UV and most chemical mutagenesis
      in Escherichia coli. The closely related species Salmonella typhimurium has two
      sets of umuDC-like operons, umuDCST on the chromosome and samAB on a 60-MDa
      cryptic plasmid. The roles of the umuDC-like operons in chemically induced
      frameshift mutagenesis of the hisD3052 allele of S. typhimurium were
      investigated. Introduction of a pBR322-derived plasmid carrying umuDCST increased
      the rate of reversion of hisD3052, following treatment with 1-nitropyrene (1-NP)
      or 1,8-dinitropyrene (1,8-DNP) tenfold and fivefold, respectively, whereas it did
      not substantially increase the rate of reversion induced by other frameshift
      mutagens, i.e. 2-nitrofluorene (2-NF) and 2-amino-3-methyldipyrido[1,2-a:3',2'
      d]imidazole (Glu-P-1). Introduction of a pBR322-derived plasmid carrying samAB
      did not increase the incidence of reversion of hisD3052 observed with any of the
      mutagens examined. Deletion of umuDCST substantially lowered the reversion rate
      induced by 1-NP or 1,8-DNP, but it did not affect reversion induced by 2-NF, Glu
      P-1 or N-hydroxyacetylaminofluorene (N-OH-AAF). Deletion of samAB had little
      impact on reversion incidence induced by any of the five frameshift mutagens. DNA
      amplification using the polymerase chain reaction technique followed by
      restriction enzyme analysis using BssHII, suggested that the mutations induced by
      the five frameshift mutagens were all CG deletions at the CGCGCGCG sequence in
      hisD3052. These results suggest that umuDCST, but not samAB, is involved in the 
      2 frameshift mutagenesis induced by 1-NP and 1,8-DNP at the repetitive CG
      sequence, whereas neither operon participates in induction of the same type of
      mutations by 2-NF, Glu-P-1 or N-OH-AAF.

PMID- 7715608
TI  - Molecular cloning, sequencing and sequence analysis of the fox-2 gene of
      Neurospora crassa encoding the multifunctional beta-oxidation protein.
AB  - We present the molecular cloning and sequencing of genomic and cDNA clones of the
      fox-2 gene of Neurospora crassa, encoding the multifunctional beta-oxidation
      protein (MFP). The coding region of the fox-2 gene is interrupted by three
      introns, one of which appears to be inefficiently spliced out. The encoded
      protein comprises 894 amino acid residues and exhibits 45% and 47% sequence
      identity with the MFPs of Candida tropicalis and Saccharomyces cerevisiae,
      respectively. Sequence analysis identifies three regions of the fungal MFPs that
      are highly conserved. These regions are separated by two segments that resemble
      linkers between domains of other MFPs, suggesting a three-domain structure. The
      first and second conserved regions of each MFP are homologous to each other and
      to members of the short-chain alcohol dehydrogenase family. We discuss these
      homologies in view of recent findings that fungal MFPs contain enoyl-CoA
      hydratase 2 and D-3-hydroxyacyl-CoA dehydrogenase activities, converting trans-2
      enoyl-CoA via D-3-hydroxyacyl-CoA to 3-ketoacyl-CoA. In contrast to its
      counterparts in yeasts, the Neurospora MFP does not have a C-terminal sequence
      resembling the SKL motif involved in protein targeting to microbodies.

PMID- 7715610
TI  - Proteasomes (prosomes) inhibit the translation of tobacco mosaic virus RNA by
      preventing the formation of initiation complexes.
AB  - Proteasomes (prosomes) are large multiprotein complexes. They are involved in
      protein degradation of ubiquitin-conjugated proteins and in the generation of MHC
      class I peptides. We gave further evidence that they interfere with in vitro
      protein synthesis. Proteasomes inhibit the translation of Tobacco mosaic virus
      RNA. Analysis of cell-free systems by sucrose gradient centrifugation revealed
      that they prevent the formation of 80S initiation complexes but not the early
      phase of initiation.

PMID- 7715611
TI  - A retinoic acid-inducible skin-specific gene (RIS-1/psoriasin): molecular cloning
      and analysis of gene expression in human skin in vivo and cultured skin cells in
      vitro.
AB  - A retinoic acid (RA) inducible skin-specific gene transcript (RIS-1) was isolated
      by differential hybridization screening of a RA-treated human skin cDNA library.
      The library was constructed from pooled RNA derived from normal adult human skin
      treated with all trans-RA for 4 h (n = 6) and 12 h (n = 6) in vivo. RIS-1 cDNA
      corresponded to a 0.6 kb transcript that was barely detectable in normal adult
      human skin but was significantly induced by 8 h in RA-treated compared to vehicle
      treated skin (range 1.1-3.6 fold). Prolonged RA treatment for up to 24 h further
      increased relative RIS-1 mRNA levels by 1.3-5.5 fold. HPLC analysis of the RA
      content of 0.1% RA-treated skin in vivo revealed significant levels at 6 h (18.8
      120.6 ng RA/g wet weight tissue; approximately 240 nM), immediately preceding the
      time point at which the increased RIS-1 mRNA level was first seen. This
      concentration of RA also induced the mRNA levels for cellular RA binding protein
      II (1.6-19 fold), a marker of RA activity in human skin. RIS-1 mRNA was detected
      by Northern and dot blotting only in normal skin but not in any other normal
      human tissues examined, indicating a tissue-specific pattern of gene expression.
      RIS-1 transcripts were detected at very low levels in untreated cultured human
      epidermal keratinocytes, while no expression was seen in dermal fibroblasts and
      melanocytes, the other major cell types in skin. Southern analysis of human and
      mouse DNA indicated the existence of evolutionarily conserved sequences for RIS-1
      between these two species. The polypeptide sequence derived from the partial RIS
      1 cDNA was found to be identical to the calcium binding domain found in
      'psoriasin', a gene whose expression appears to be increased in the skin of
      psoriasis patients.

PMID- 7715612
TI  - In vitro and in vivo genotoxicity of hormonal drugs. VI. Fluoxymesterone.
AB  - Genotoxic evaluation of a commonly used synthetic steroidal androgen,
      fluoxymesterone, was undertaken using a combination of in vitro and in vivo
      assays. The clastogenic potential of fluoxymesterone was evident from the
      chromosome aberrations and sister chromatid exchanges induced by it in the
      cultured human lymphocytes and also from the increased frequencies of micronuclei
      and sister chromatid exchanges in bone marrow cells of mice. However, in Ames
      Salmonella assay both with and without S9 mix and in host-mediated assay using
      bacterial strains of S. typhimurium as indicator organism, fluoxymesterone did
      not cause any significant increase/decrease in His+ revertants.

PMID- 7715609
TI  - Organization of (pre-)mRNA metabolism in the cell nucleus.

PMID- 7715613
TI  - Increased genotoxicity of acetylaminofluorene by modulators of multixenobiotic
      resistance mechanism: studies with the fresh water clam Corbicula fluminea.
AB  - The presence of a 'multixenobiotic resistance' [MXR] mechanism in gills of the
      freshwater clam Corbicula fluminea was investigated. Western blot analyses of
      membrane vesicles from gills, applying antibodies to vertebrate P170 multidrug
      resistance (MDR) protein, revealed a 135 kDa immunoreactive protein. Verapamil
      caused a reduction of 3H-vincristine (3H-VCR) binding onto vesicles from clam.
      Exposure of clams to 3H-VCR in the presence of verapamil or staurosporine (STP)
      enhanced the accumulation of 3H-VCR over control values. Furthermore, clams were
      exposed instead to VCR, to a model carcinogen, 2-acetylaminofluorene (AAF), to
      determine the verapamil- and STP-dependent increase of single-strand breaks
      (SSBs) in DNA from gills of this organism. Verapamil caused no or little increase
      of SSBs induced by exposure to 0.01 or 0.10 microM AAF, respectively, as measured
      by the alkaline elution technique. In contrast, in the presence of STP a highly
      significant and dose-dependent enhancement of AAF-mediated SSBs was measured
      already at exposure to 0.01 microM AAF. These data indicate (i) that the clam C.
      fluminea is provided with a P-glycoprotein-like element of the MDR-mechanism,
      (ii) that this system can be poisoned by chemosensitizers such as verapamil and
      STP, (iii) the role of protein kinase C in the regulation of MXR function and
      (iv) the importance of the MXR modulators for the assessment of ecotoxicological
      effects of pollutants.

PMID- 7715614
TI  - The micronucleus assay in Crassostrea gigas for the detection of seawater
      genotoxicity.
AB  - The micronucleus (MN) test was performed in vivo and in vitro on the oyster
      Crassostrea gigas to evaluate the genotoxic effect of the marine environment. In
      vitro tests were carried out on adult and young (spat) specimens exposed to
      benzo[a]pyrene (BaP: 0.5, 5, 500 and 1000 micrograms.l-1) and an effluent (5, 50,
      75 and 100%) of Seine Bay, one of the most highly contaminated sites in France.
      MN frequency observed after 48 h exposure to the two pollutants was much greater
      in adults than spats. A preliminary test of the genotoxic effect of BaP (0.05,
      0.5, 1 and 500 micrograms.l-1), cupric sulfate (10, 25, 50 and 100 micrograms.l
      1) and a paper mill effluent (1, 3, 10 and 30 mg.l-1) was performed in C. gigas
      heart cells cultured for 6 days. Comparison of the MN assay with the C. gigas
      larva test showed the clastogenic action of BaP and the toxic effect of cupric
      sulfate on culture cells as well as the slighter toxic effect of paper mill
      effluent on spats. An in vivo study was conducted in an oyster-farming area
      contaminated by cadmium and copper. MN frequency was not very sensitive to a
      pollution gradient but showed high interindividual variability. The absence of
      precise criteria for MN identification in mollusks and the identification of
      highly basophilic spherical inclusions in the cytoplasm of gill tissue hemocytes
      in oysters during viral infection are handicap for application of the micronuclei
      assay in the marine environment. Another limitation of the assay is the
      particularly onerous requirement for manual observation. Optimization of the
      assay by automated analysis is necessary but can only be achieved if cytologic
      preparations are of good quality.

PMID- 7715615
TI  - Comparative study on Salmonella mutagenicity and on cytogenetic and
      antineoplastic effects induced by cyclophosphamide and 3-aminobenzamide in cells
      of three transplantable tumours in vivo.
AB  - Synergistically enhanced sister chromatid exchange (SCE) frequency by
      cyclophosphamide (CP) was observed when L1210 lymphoid tumor cells were exposed
      in vivo to a non-toxic concentration of 3-aminobenzamide (3-AB). Additive effects
      in SCE induction in vivo were observed when either Ehrlich ascites tumor (EAT)
      cells or P388 lymphocytic leukemia cells treated with CP were exposed to 3-AB in
      vivo. 3-AB enhanced the survival time of L1210 tumor bearing BDF1 mice treated
      with CP. However, the combined CP plus 3-AB treatment did not increase the
      survival of either EAT BALB/c- or P388 BDF1-tumor bearing mice compared with the
      effect on survival by CP alone. Therefore the in vivo differential antitumor
      effect, by CP in conjunction with 3-AB, appears to correlate well with the in
      vivo differential effect on cytogenetic damage caused by the combined CP plus 3
      AB treatment. In the Salmonella typhimurium/mammalian microsome test CP appears
      to have a dose dependent ability to induce base-pair substitutions in strains TA
      100 and TA 1535 and frameshift mutations in strains TA 98 and TA 1537. Both types
      of mutation were synergistically increased in the presence of 3-AB.

PMID- 7715616
TI  - Cytogenetic biomonitoring of a population of children allegedly exposed to
      environmental pollutants. Phase 2: Results of a three-year longitudinal study.
AB  - Our previous cytogenetic biomonitoring of a group of inhabitants in a village
      (Mellery, Belgium) where exposure to a mixture of toxic environmental pollutants,
      (probably originating from a neighbouring chemical waste disposal site) was
      suspected, showed that difference in the SCE and HFC bioassays was more
      pronounced for children. The results of follow-up study in 1992 confirmed this
      surprising conclusion by an even higher incidence. As very few studies have been
      performed on the levels of children's biomarkers, this group of exposed
      populations needed to be explored further. Do children residing in the vicinity
      of hazardous waste sites indeed represent a population at higher risk? In the
      present study, we compare the performance of various bioassays (SCE, HFC, SSB and
      MN) in extended exposed and reference children's groups. Simultaneously, in the
      exposed group, we followed variation in the lymphocyte SCE frequencies as a
      function of time. Reversibility of the latter biomarker was ascertained
      subsequent to a preliminary technical remediation of the disposal site. We
      compared these data with those obtained from a synchronous cross-sectional study
      on a group of children living near a similar chemical disposal site. The two
      exposed populations did not differ from the reference population regarding to the
      SCE and HFC mean levels. Comparisons of the mean levels of the two other
      biomarkers, SSB and MN, showed no difference between the Mellery exposed children
      and the reference group from Wavre whereas significant differences appeared when
      the Hensies group is compared either to the Mellery or to the Wavre reference
      group.

PMID- 7715617
TI  - Inhibitory effects of paracetamol on DNA repair in mammalian cells.
AB  - Paracetamol blocks DNA replication by inhibiting deoxyribonucleotide (dNTP)
      synthesis and may therefore also interfere with DNA repair. In the present work
      various mammalian cell types were treated with genotoxic agents and allowed to
      repair in the presence or absence of paracetamol. Alkaline elution was used to
      assay DNA single-strand breaks plus alkali-labile sites (= SSBs). Resting human
      mononuclear blood cells (MNC) exposed to 4-nitroquinoline N-oxide (NQO, 3 microM)
      plus 0.3 mM paracetamol contained twice as many DNA SSBs compared to MNC exposed
      to NQO alone, and the level of SSBs decreased more slowly during repair in the
      presence of paracetamol. Deoxyribonucleosides reversed the effects of
      paracetamol. SSBs induced by MMS or X-rays (2.6 Gy) were not increased by
      paracetamol. Resting and growth-stimulated MNC, HL-60 cells, rat hepatocytes and
      human fibroblasts exposed to UV-C (3-12 J/m2) showed varying levels of transient
      SSBs formed during repair but these were consistently higher in the presence of
      paracetamol (0.3-1 mM). In rat testicular cells SSBs were induced by NQO and the
      levels were further increased in the presence of paracetamol, whereas after UV
      almost no SSBs were detected during repair. The cell-type specific levels of
      transient SSBs after UV did not correlate with the rate of incision of DNA
      lesions, measured as the rate of SSB accumulation in the presence of repair
      inhibitors Ara C plus hydroxyurea. Transient SSBs were present in resting MNC for
      at least 24 h after UV and paracetamol increased these breaks 4-fold however the
      overall rate of removal of excisable photodamage during repair did not appear to
      be reduced by the presence of paracetamol. The present data indicate that
      paracetamol interferes with nucleotide excision repair in several mammalian cell
      types. This constitutes a mechanism by which paracetamol may contribute to
      genotoxicity in humans.

PMID- 7715618
TI  - Assessment of micronucleus induction in SCCVII cells treated with bioreductive
      agents, WIN 59075 (SR 4233) and mitomycin C, under aerobic and hypoxic
      conditions.
AB  - WIN 59075 (SR4233, tirapazamine) is a promising bioreductive antitumor agent
      preferentially more toxic to hypoxic cells and presently undergoing phase I
      clinical trials. In this investigation, we have examined the applicability of the
      cytokinesis-block micronucleus assay to assess the effects of bioreductive
      agents. SCCVII tumor cells were treated with WIN 59075 or mitomycin C at various
      concentrations under aerobic and hypoxic conditions. Significant induction of
      micronuclei in binucleate cells was demonstrated in a dose-dependent fashion and
      it appeared to be strongly correlated with the loss of clonogenicity in the
      colony assay. Both agents showed selectively higher toxicity to hypoxic cells
      than to aerobic cells and the ratios of the concentrations required to obtain the
      equivalent effects under aerobic and hypoxic conditions could be also estimated
      by this method as follows: the hypoxic toxicity ratios were 120-130 for WIN 59075
      and 3.0-3.3 for mitomycin C. For several favorable characteristics, the
      cytokinesis-block micronucleus assay can provide an alternative, rapid, and
      reproducible means for evaluation of antitumor activities from chromosomal
      breakage caused by the bioreductive agents.

PMID- 7715619
TI  - A comparison of the mutagenicity of mainstream cigarette smoke condensates from a
      representative sample of the U.S. cigarette market with a Kentucky reference
      cigarette (K1R4F).
AB  - The Salmonella mutagenicity assay has been used to investigate the mutagenicity
      of cigarette smoke and cigarette smoke condensate. The Kentucky reference (K1R4F)
      cigarette is designed to be representative of full-flavor, low-tar cigarettes
      sold in the U.S. and to serve as a reference standard for comparative studies on
      the chemistry and biological activities of cigarette smoke and condensate. The
      objective of this study was to determine if the mutagenicity of mainstream smoke
      condensate from the K1R4F, as measured by the Salmonella mutagenicity assay, is
      representative of the mutagenic activity of U.S. cigarettes. Mainstream smoke
      condensates prepared in dimethyl sulfoxide from the K1R4F and 73 brand styles
      (representing greater than 70% of the total U.S. cigarette market) were assayed
      using Salmonella typhimurium TA98 and TA100 (+S9) at concentrations of 0, 25, 50,
      75, 100, 125 and 250 micrograms/plate. Revertants/mg condensate were determined
      by calculating the slopes of the dose-response curves using linear and nonlinear
      regression models. Revertants/cigarette were determined by multiplying the
      revertants/mg condensate by the mg condensate/cigarette. No significant
      differences (p > 0.05) were observed between the mean mutagenicity of U.S. market
      and K1R4F mainstream smoke condensates in terms of revertants/mg condensate or
      revertants/cigarette. Increased variability in mutagenicity was observed among
      the U.S. brands versus that of the K1R4F. This is not surprising since
      variability among the U.S. brands would be expected to have both measurement
      error and brand style variability while the K1R4F variability contains only the
      measurement error portion. These results demonstrate that the K1R4F is a
      representative model for the U.S. cigarette market in comparative Salmonella
      mutagenicity studies using mainstream smoke condensates.

PMID- 7715620
TI  - Cytotoxicity and genotoxicity of wood drying condensate from Southern Yellow
      Pine: an in vitro study.
AB  - We tested condensates from Southern Yellow Pine for potential cytotoxicity and
      genotoxicity in CHO-WBL and human peripheral blood lymphocytes (PBL) in the
      absence of S-9 activation. Cytotoxicity was evaluated by the Trypan blue
      exclusion assay, mitotic index (MI) and proliferative rate index (PRI).
      Genotoxicity was measured by the chromosome aberration (CA) assay and sister
      chromatid exchange (SCE) analysis. Both cytotoxic and genotoxic effects were
      observed. Laboratory-generated Southern Yellow Pine condensate reduced the
      viability of CHO-WBL cells. The number of viable cells was roughly inversely
      proportional to dosage over a range of 100% to 31% in treated groups, in both
      experiments, as compared to 2.6 x 10(5) (100%) in the control. The MI data in
      both CHO cells and PBL also showed an inverse correlation. The highest scorable
      dose limited by toxicity was determined to be 1 ml of Southern Yellow Pine
      condensate in 10 ml total of medium. Lastly, a dose response curve was observed
      in CHO cells, as well as in PBL, using the CA assay and also with the SCE
      analysis. The present findings corroborate the results from Ames testing and
      represent the only information currently available on the genotoxic potential of
      these chemicals.

PMID- 7715621
TI  - Motor unit estimation: anxieties and achievements.
AB  - The history of motor unit number estimation (MUNE) is given, together with brief
      descriptions of the various methods presently available. A small muscle of the
      hand contains about 100 motor units and greater numbers are found in larger
      muscles; beyond 60 years the numbers begin to decline. In ALS approximately half
      the motor units cease to function within 6 months of the involvement of the
      motoneuron pool, while in adult spinal muscular atrophy further loss may not
      occur over several years. The reduction in MUNE values in myotonic dystrophy
      remains an enigma, but even more curious are the losses and subsequent recoveries
      occasionally observed in hyperthyroidism and chronic renal failure; possibly,
      nontransmitting ("silent") synapses are involved. MUNE may also be used to study
      CNS problems such as hemiplegia and congenital brachial palsy. The availability
      of more powerful computers for EMG should lead to advances in MUNE.

PMID- 7715622
TI  - Progression of neuropathy in peripheral arterial disease.
AB  - Atherosclerotic peripheral arterial disease (PAD) can cause muscle denervation,
      but whether it is associated with more severe peripheral nerve disease is not
      clear. Equally unclear is the effect of exercise training on the neuromuscular
      aspects of this disease. We performed serial electrophysiologic studies (nerve
      conduction studies and quantitative electromyography) and muscle strength
      assessment on 16 patients with moderately severe PAD. Seven of the patients were
      assigned to a natural history (control) group and 9 to an exercise training
      group. Over study periods ranging from 3 to 23 months, 6 of 7 patients in the
      control group and 8 of 9 patients in the exercise training group showed
      progression of multifocal neuropathic disease in their ischemic legs. For
      equivalent lengths of time, the degree of neuropathic progression was not
      significantly different between the control and exercise training groups. There
      was a significant decline in muscle strength for the control group but not for
      the exercise training group. These results demonstrate that PAD can be associated
      with the development of a multifocal predominantly motor neuropathy, which is
      most likely ischemic in etiology. Furthermore, exercise training does not pose an
      additional risk for the development of neuropathy in patients with moderately
      severe PAD.

PMID- 7715623
TI  - Failure of anti-GM1 IgG or IgM to induce conduction block following intraneural
      transfer.
AB  - In order to confirm the reported pathogenicity of human antibodies to
      monosialoganglioside GM1, immunoglobulin fractions with high anti-GM1 IgG or IgM
      titers were prepared from patients with Guillain-Barre syndrome and multifocal
      motor neuropathy respectively. These fractions were injected intraneurally into
      rat tibial nerves with fresh human complement. Neither the anti-GM1 IgG nor the
      anti-GM1 IgM fraction induced significant focal conduction block or slowing
      compared to a pooled fraction prepared from 5 normal individuals. In contrast,
      rabbit experimental allergic neuritis serum included as a positive control was
      highly active. Transverse sections of injected nerve failed to show evidence of
      demyelination. Staining for human immunoglobulin in cryostat sections showed the
      presence of injected anti-GM1 antibody bound to nodes of Ranvier up to 6 days
      following intraneural transfer. These data fail to confirm previous reports of
      conduction block from intraneural transfer of anti-GM1 serum and suggest that
      such electrophysiological effects may be the result of factors other than or in
      addition to anti-GM1 antibodies.

PMID- 7715624
TI  - Sympathetic sudomotor function and aging.
AB  - Many studies have reported the influence of aging on different portions of the
      autonomic nervous system components but only partially for the sympathetic
      cholinergic system. We evaluated postganglionic sudomotor function in 196 healthy
      subjects, 104 women and 92 men, by determining sweat gland density (SGD) per
      square centimeter of skin, on the dorsum of the hand and foot, with the
      impression mold technique. The age range was from 5 to 84 years. A significant
      decrease of SGD was observed in both hand and foot in relation to age (P <
      0.001). The ANOVA analysis of foot data shows that age is the only significant
      factor for SGD reduction. In the hand, both sex and body surface area are
      significant covariates with age. The dorsum of the foot is the most appropriate
      place to examine sweating in studies of aging. The lower normal limits for SGD in
      the foot are 213/cm2 for subjects younger than 30 years, 199/cm2 for those from
      30 to 59 years, and 123/cm2 for subjects over 59 years old.

PMID- 7715625
TI  - Differentiation between axonal and demyelinating neuropathies: identical segments
      recorded from proximal and distal muscles.
AB  - The presence of significant slowing of motor nerve conduction velocity is
      considered one of the electrodiagnostic hallmarks of demyelinating neuropathies;
      however, slowing of conduction velocity may also accompany severe axonal loss.
      When compound muscle action potential (CMAP) amplitudes are markedly reduced, it
      is frequently difficult to determine if conduction velocity slowing is due to
      axonal loss with dropout of the fastest conducting fibers or demyelination. To
      evaluate the relationship between conduction velocity and axonal dropout, we
      compared conduction velocities through the same segment of nerve recording from
      distal and proximal peroneal muscles in patients with chronic neuropathies, in
      patients with motor neuron disease, and in control subjects. In controls and
      patients with motor neuron disease, conduction velocities were normal with no
      significant difference between proximal and distal sites. In patients with axonal
      neuropathies, conduction velocities were preferentially slowed when recording
      from distal muscles and relatively normal when recording from proximal sites.
      Patients with demyelinating neuropathies showed marked slowing of conduction at
      both sites. We conclude that comparing conduction velocity obtained from proximal
      versus distal muscle recordings provides a simple, reliable aid for
      differentiating between chronic axonal and demyelinating polyneuropathies,
      especially in cases with conduction velocity slowing and low CMAP amplitudes.

PMID- 7715626
TI  - Anti-Gal-C antibody in autoimmune neuropathies subsequent to mycoplasma
      infection.
AB  - Four of 82 patients with Guillain-Barre syndrome (GBS) and 1 of 12 with
      multifocal motor neuropathy (MMN), who previously had had Mycoplasma pneumoniae
      infections, had serum antibody to galactocerebroside (Gal-C). Two patients with
      GBS without mycoplasma infection also had anti-Gal-C antibody, whereas none of
      the normal or the disease controls had it. As Gal-C is a major glycolipid antigen
      in myelin, anti-Gal-C antibody may function in the pathogenesis of autoimmune
      demyelinative neuropathies. Mycoplasma pneumoniae appears to be an important
      preceding infectious agent in autoimmune neuropathies with anti-Gal-C antibody.

PMID- 7715627
TI  - The electrophysiologic features of sciatic neuropathy in 100 patients.
AB  - We reviewed the electrophysiologic data of 100 consecutive patients with sciatic
      neuropathy in order to better understand this disorder. Most patients (93%) had
      electrodiagnostic signs of significant axonal loss. Seven patients had
      predominantly signs of demyelination; 6 were due to compression and 1 was
      idiopathic. The peroneal division was more severely affected than the tibial
      division in 64% of patients. Tibialis anterior EMGs were abnormal in 92%, and the
      EDB CMAP was low in amplitude or absent in 80%. CMAP and SNAP amplitudes and EMGs
      were all normal in the tibial division in 12%. In contrast, the tibial division
      was more severely affected in only 8 patients. Of those, 5 were due to thigh
      trauma (gunshot wounds or femur fracture), 2 from gunshot wounds to the hip, and
      the other was chronic and idiopathic. Sciatic neuropathies are commonly, but not
      always, axonal loss lesions that affect the peroneal greater than tibial
      division.

PMID- 7715628
TI  - Calcium exchange hypothesis of skeletal muscle fatigue: a brief review.
AB  - Skeletal muscle fatigue is often associated with diminished athletic performance
      and work productivity as well as increased susceptibility to injury. The exact
      cause of muscle fatigue probably involves a number of factors which influence
      force production in a manner dependent on muscle fiber type and activation
      pattern. However, a growing body of evidence implicates alterations in
      intracellular Ca2+ exchange as a major role in the fatigue process. These changes
      are thought to occur secondary to reductions in the rates of Ca2+ uptake and
      release by the sarcoplasmic reticulum (SR). This hypothesis is based on the
      finding that peak myoplasmic Ca2+ concentration ([Ca2+]i) is reduced as force
      declines during fatigue. In addition, direct measurements of Ca2+ uptake and
      release show that fatiguing activity causes intrinsic alterations in the
      functional properties of the SR. We also propose that fatigue-induced alterations
      in Ca2+ exchange may be beneficial, reducing the rate of energy utilization by
      the muscle fiber and preventing irreversible damage to the cell.

PMID- 7715629
TI  - Can the size principle be detected in conventional EMG recordings?
AB  - According to Henneman's size principle, small motor units are recruited before
      large ones. It is commonly believed that this can be detected in routine
      conventional EMG recordings even among the earliest recruited motor units. That
      is, the MUP amplitude, area, and thickness should increase with recruitment
      order. We studied the first four motor unit potentials (MUPs) recruited within
      the pickup area of the electrodes. Data were obtained from 179 different sites in
      monopolar recordings and in 153 concentric recordings from 5 health subjects. In
      the pooled material, amplitude, area, and thickness increased slightly between
      consecutively recruited MUPs. However, at individual recording sites the size of
      consecutively recruited MUPs varied considerably. At some recording sites the
      first recruited MUP had the largest amplitude and the later MUPs has successively
      smaller amplitudes. We conclude that, at individual recording sites, the size
      principle cannot be detected in low threshold motor units with monopolar or
      concentric EMG electrodes. The reason for this is the small uptake area of these
      electrodes in relation to the motor unit territory.

PMID- 7715630
TI  - Late motor involvement in cases presenting as "chronic sensory demyelinating
      polyneuropathy".
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is usually characterized
      by prominent motor deficits. A pure sensory presentation, labeled chronic sensory
      demyelinating neuropathy (CSDN), has been reported, but it is unclear if this
      neuropathy is a distinct clinical and immunologic entity or merely the sensory
      presentation of the more usual sensorimotor CIDP. We describe 5 patients with
      what initially appeared to be CSDN; 3 subsequently developed substantial weakness
      coincident with the electrophysiologic appearance of multifocal motor conduction
      block. These cases indicate that, in some cases, CSDN may be a transitional
      clinical stage of CIDP in which the more usual sensorimotor deficits develop
      later. Immune-based therapy, including intravenous immunoglobulin, was found to
      be effective in both the pure sensory and sensorimotor types.

PMID- 7715632
TI  - Essence, investigation, and management of "neuropathic" pains: hopes from
      acknowledgment of chaos.

PMID- 7715631
TI  - Segmental median nerve conduction measurements discriminate carpal tunnel
      syndrome from diabetic polyneuropathy.
AB  - Median nerve conduction has been compared in CTS, with or without diabetes, and
      diabetic polyneuropathy. Approximately 90% of hands were correctly predicted as
      CTS or diabetic polyneuropathy by a comparison including the median antidromic
      sensory nerve conduction velocities in the elbow-to-wrist segment, wrist-to-palm
      segment, palm-to-finger segment, and the amplitude of the sensory nerve action
      potential. CTS with diabetes could not be distinguished from CTS without
      diabetes. The association between proximal and distal nerve conduction velocities
      was similar in CTS and diabetic polyneuropathy. A study in motor fibers showed
      that the hands could be classified through a combination of M-wave latency and
      the more proximal motor nerve conduction velocity measurements. Independent of
      severity, motor and sensory nerve conduction was influenced to an equal degree in
      CTS and diabetic polyneuropathy. The hypothesis that both CTS and diabetic
      polyneuropathy can be associated with neural ischemia is discussed.

PMID- 7715633
TI  - Essence, investigation, and management of "neuropathic" pains: hopes from
      acknowledgment of chaos.

PMID- 7715634
TI  - Electrophysiological evidence of trigeminal root damage after trichloroethylene
      exposure.

PMID- 7715635
TI  - Accommodation in single human nerve fibers in vivo.

PMID- 7715636
TI  - Predictive value of the prolonged exercise test in hypokalemic paralytic attack.

PMID- 7715637
TI  - Myopathy, antineutrophil cytoplasmic antibodies, and glomerulonephritis.

PMID- 7715638
TI  - Ekbom's syndrome.

PMID- 7715639
TI  - Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia.
      Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia.
AB  - BACKGROUND: In a previous open-label study of hydroxyurea therapy, the synthesis
      of fetal hemoglobin increased in most patients with sickle cell anemia, with only
      mild myelotoxicity. By inhibiting sickling, increased levels of fetal hemoglobin
      might decrease the frequency of painful crises. METHODS: In a double-blind,
      randomized clinical trial, we tested the efficacy of hydroxyurea in reducing the
      frequency of painful crises in adults with a history of three or more such crises
      per year. The trial was stopped after a mean follow-up of 21 months. RESULTS:
      Among 148 men and 151 women studied at 21 clinics, the 152 patients assigned to
      hydroxyurea treatment had lower annual rates of crises than the 147 patients
      given placebo (median, 2.5 vs. 4.5 crises per year, P < 0.001). The median times
      to the first crisis (3.0 vs. 1.5 months, P = 0.01) and the second crisis (8.8 vs.
      4.6 months, P < 0.001) were longer with hydroxyurea treatment. Fewer patients
      assigned to hydroxyurea had chest syndrome (25 vs. 51, P < 0.001), and fewer
      underwent transfusions (48 vs. 73, P = 0.001). At the end of the study, the doses
      of hydroxyurea ranged from 0 to 35 mg per kilogram of body weight per day.
      Treatment with hydroxyurea did not cause any important adverse effects.
      CONCLUSIONS: Hydroxyurea therapy can ameliorate the clinical course of sickle
      cell anemia in some adults with three or more painful crises per year. Maximal
      tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic
      effect. The beneficial effects of hydroxyurea do not become manifest for several
      months, and its use must be carefully monitored. The long-term safety of
      hydroxyurea in patients with sickle cell anemia is uncertain.

PMID- 7715640
TI  - Mutations of the Connexin43 gap-junction gene in patients with heart
      malformations and defects of laterality.
AB  - BACKGROUND: Gap junctions are thought to have a crucial role in the synchronized
      contraction of the heart and in embryonic development. Connexin43, the major
      protein of gap junctions in the heart, is targeted by several protein kinases
      that regulate myocardial cell-cell coupling. We hypothesized that mutations
      altering sites critical to this regulation would lead to functional or
      developmental abnormalities of the heart. METHODS: Connexin43 DNA from 25 normal
      subjects and 30 children with a variety of congenital heart diseases was
      amplified by the polymerase chain reaction and sequenced. Mutant DNA was
      expressed in cell culture and examined for its effect on the regulation of cell
      cell communication. RESULTS: The 25 normal subjects and 23 of the 30 children
      with heart disease had no amino acid substitutions in connexin43. All six
      children with syndromes that included complex heart malformations had
      substitutions of one or more phosphorylatable serine or threonine residues. Four
      of these children had two independent mutations, suggesting an autosomal
      recessive disorder. Five of these children had substitutions of proline for
      serine at position 364. A seventh child, with a different heart condition, also
      had a point mutation in connexin43. Transfected cells expressing the Ser364Pro
      mutant connexin43 sequence showed abnormalities in the regulation of cell-cell
      communication, as compared with cells expressing normal connexin43. CONCLUSIONS:
      Mutations in the connexin43 gap-junction gene, which lead to abnormally regulated
      cell-cell communication, are associated with visceroatrial heterotaxia.

PMID- 7715642
TI  - Images in clinical medicine. Ostium secundum atrial septal defect.

PMID- 7715641
TI  - Heparin-induced thrombocytopenia in patients treated with low-molecular-weight
      heparin or unfractionated heparin.
AB  - BACKGROUND: Heparin-induced thrombocytopenia, defined by the presence of heparin
      dependent IgG antibodies, typically occurs five or more days after the start of
      heparin therapy and can be complicated by thrombotic events. The frequency of
      heparin-induced thrombocytopenia and of heparin-dependent IgG antibodies, as well
      as the relative risk of each in patients given low-molecular-weight heparin, is
      unknown. METHODS: We obtained daily platelet counts in 665 patients in a
      randomized, double-blind clinical trial comparing unfractionated heparin with low
      molecular-weight heparin as prophylaxis after hip surgery. Heparin-induced
      thrombocytopenia was defined as a decrease in the platelet count below 150,000
      per cubic millimeter that began five or more days after the start of heparin
      therapy, and a positive test for heparin-dependent IgG antibodies. We also tested
      a representative subgroup of 387 patients for heparin-dependent IgG antibodies
      regardless of their platelet counts. RESULTS: Heparin-induced thrombocytopenia
      occurred in 9 of 332 patients who received unfractionated heparin and in none of
      333 patients who received low-molecular-weight heparin (2.7 percent vs. 0
      percent; P = 0.0018). Eight of the 9 patients with heparin-induced
      thrombocytopenia also had one or more thrombotic events (venous in 7 and arterial
      in 1), as compared with 117 of 656 patients without heparin-induced
      thrombocytopenia (88.9 percent vs. 17.8 percent; odds ratio, 36.9; 95 percent
      confidence interval, 4.8 to 1638; P < 0.001). In the subgroup of 387 patients,
      the frequency of heparin-dependent IgG antibodies was higher among patients who
      received unfractionated heparin (7.8 percent, vs. 2.2 percent among patients who
      received low-molecular-weight heparin; P = 0.02). CONCLUSIONS: Heparin-induced
      thrombocytopenia, associated thrombotic events, and heparin-dependent IgG
      antibodies are more common in patients treated with unfractionated heparin than
      in those treated with low-molecular-weight heparin.

PMID- 7715643
TI  - Images in clinical medicine. Ostium secundum atrial septal defect.

PMID- 7715644
TI  - A randomized trial of care in a hospital medical unit especially designed to
      improve the functional outcomes of acutely ill older patients.
AB  - BACKGROUND: Older persons who re hospitalized for acute illnesses often lose
      their independence and are discharged to institutions for long-term care.
      METHODS: We studied 651 patients 70 years of age or older who were admitted for
      general medical care at a teaching hospital; these patients were randomly
      assigned to receive usual care or to be cared for in a special unit designed to
      help older persons maintain or achieve independence in self-care activities. The
      key elements of this program were a specially prepared environment (with, for
      example, uncluttered hallways, large clocks and calendars, and handrails);
      patient-centered care emphasizing independence, including specific protocols for
      prevention of disability and for rehabilitation; discharge planning with the goal
      of returning the patient to his or her home; and intensive review of medical care
      to minimize the adverse effects of procedures and medications. The main outcome
      we measured ws the change from admission to discharge in the number of five basic
      activities of daily living (bathing, getting dressed, using the toilet, moving
      from a bed to a chair, and eating) that the patient could perform independently.
      RESULTS: Twenty-four patients in each group died in the hospital. At the time of
      discharge, 65 (21 percent) of the 303 surviving patients in the intervention
      group were classified as much better in terms of their ability to perform basic
      activities of daily living, 39 (13 percent) as better, 151 (50 percent) as
      unchanged, 22 (7 percent) as worse, and 26 (9 percent) as much worse. In the
      usual care group, 40 (13 percent) of the 300 surviving patients were classified
      as much better, 33 (11 percent) as better, 163 (54 percent) as unchanged, 39 (13
      percent) as worse, and 25 (8 percent) as much worse (P = 0.009). The difference
      between the groups remained significant (P = 0.04) in a multivariable model in
      which we controlled for potentially confounding base-line characteristics of the
      patients. Lengths of stay and hospital charges were similar in the two groups.
      Fewer patients assigned to the intervention group were discharged to long-term
      care institutions (43 patients [14 percent], as compared with 67 patients [22
      percent] in the usual-care group; P = 0.01). Among the 493 patients discharged to
      private homes, similar proportions (about 10 percent) in the two groups were
      admitted to long-term care institutions during the three months after discharge.
      CONCLUSIONS: Specific changes in the provision of acute hospital care can improve
      the ability of a heterogeneous group of acutely ill older patients to perform
      basic activities of daily living at the time of discharge from the hospital and
      can reduce the frequency of discharge to institutions for long-term care.

PMID- 7715646
TI  - The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation.

PMID- 7715645
TI  - A randomized trial of comprehensive geriatric assessment in the care of
      hospitalized patients.
AB  - BACKGROUND: Although many studies describe benefits from the comprehensive
      assessment of elderly patients by an interdisciplinary team (comprehensive
      geriatric assessment), the most supportive evidence for the process has come from
      programs that rely on specialized inpatient units and long hospital stays. We
      examined whether an inpatient geriatric consultation service might also be
      beneficial in a trial involving four medical centers of a group-practice health
      maintenance organization (HMO). METHODS: We conducted a randomized clinical trial
      with 2353 hospitalized patients 65 years of age or older in whom at least 1 of 13
      screening criteria were present: stroke, immobility, impairment in any basic
      activity of daily living, malnutrition, incontinence, confusion or dementia,
      prolonged bed rest, recent falls, depression, social or family problems, an
      unplanned readmission to the hospital within three months of a previous hospital
      stay, a new fracture, and age of 80 years or older. Of the 1337 patients assigned
      to the experimental group, 1261 (94 percent) received a comprehensive geriatric
      assessment in the form of a consultation, with limited follow-up; the 1016
      patients assigned to the control group received usual care. The functional and
      health status of the patients was measured at base line and 3 and 12 months
      later; survival was assessed at 12 months. Subgroups of patients who might be
      presumed to benefit from comprehensive assessment were also studied. RESULTS: The
      survival rate at 12 months was 74 percent in the experimental group and 75
      percent in the control group. At base line, 3 months, and 12 months the scores of
      the two groups on measures of functional and health status were similar. The
      analysis of 16 subgroups did not identify any with either clearly improved
      functional status or improved survival. CONCLUSIONS: In this HMO, comprehensive
      geriatric assessment by a consultation team, with limited follow-up, did not
      improve the health or survival of hospitalized patients selected on the basis of
      screening criteria.

PMID- 7715647
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 15-1995. A 70-year-old woman with atrial fibrillation and the
      rapid onset of hemorrhagic manifestations.

PMID- 7715648
TI  - Heparin-induced thrombocytopenia and thrombosis.

PMID- 7715649
TI  - The value of geriatric interventions.

PMID- 7715650
TI  - Patterns of mortality from asthma.

PMID- 7715651
TI  - Patterns of mortality from asthma.

PMID- 7715652
TI  - Factor V Leiden and thrombophilia.

PMID- 7715653
TI  - Factor V Leiden and thrombophilia.

PMID- 7715654
TI  - Factor V Leiden and thrombophilia.

PMID- 7715655
TI  - Factor V Leiden and thrombophilia.

PMID- 7715656
TI  - Idiopathic dilated cardiomyopathy.

PMID- 7715657
TI  - Idiopathic dilated cardiomyopathy.

PMID- 7715658
TI  - Idiopathic dilated cardiomyopathy.

PMID- 7715659
TI  - Idiopathic dilated cardiomyopathy.

PMID- 7715661
TI  - An update on intravenous therapy.

PMID- 7715660
TI  - Primary health care goals.

PMID- 7715662
TI  - Nutrition factors in disease management.

PMID- 7715663
TI  - "Knitting and plasters" or a gold class service?. Interview by Jo Goddard.

PMID- 7715664
TI  - A situation analysis of nursing education. Part one: Conceptual framework.
AB  - A Strategic Planning Committee was established by the Transvaal Provincial
      Administration to plan for and reposition nursing education in the Transvaal.
      Various focus areas were identified, including the Focus Area Curricula. The aim
      of the Focus Area Curricula Committee is the establishment of curricula for the
      education and training of all categories of nurses to provide for the needs of
      nursing services in the Transvaal. The committee is still working towards the aim
      but a situation analysis has been completed. The purpose of this Article is to
      discuss a conceptual framework by which a logical approach to the situation
      analysis can be maintained.

PMID- 7715665
TI  - SA AIDS comic "Roxy".

PMID- 7715666
TI  - Ethical committees.

PMID- 7715667
TI  - [The midwife in South Africa. Part I--The practice of the midwife].
AB  - Part 1, of a two part series on the dilemma of the midwife in South Africa, deals
      with the practice of the midwife. It is difficult to estimate the number of
      practicing midwives, as they form part of the general nursing register. Also
      midwifery is part of the basic nurse training and is not taught as a separate
      entity. The midwife in South Africa practices in the areas of primary health
      care, hospitals, clinics, mobile clinics, homes and MOU's. The governments
      commitment to PHC will likely result in most midwives practicing in this area.
      Problems are high maternal deaths, shortages and maldistribution of midwives in
      an urban/rural context and the fragmentation and poor coordination of the health
      services. The safe motherhood initiative of the WHO has been adopted, there are
      recommendations that midwifery education be separated from general nurse
      education, and that clinical skills be strengthened. Midwifery services in South
      Africa do not fulfill the basic criteria for a PHC service.

PMID- 7715668
TI  - [The dilemma of the midwife--Part 2].
AB  - The author outlines the similarities and dissimilarities between nursing and
      midwifery and comes to the conclusion that the method of training midwives as
      part of the general nursing curriculum has advantages and disadvantages;
      advantages such as time, cost and manpower savings; disadvantages such as
      integrated course content, and lack of sufficient practical experience before
      graduating. Simulations can help with the latter, but do not provide sufficient
      skills to handle real situations. The author proposes post-basic midwifery
      internship; improved training; and broadening the functions of the midwife to
      include training and supervision of voluntary community workers and traditional
      birth attendants.

PMID- 7715669
TI  - Primary health care goals--Part 2. Primary Health Care Women United in Health.

PMID- 7715670
TI  - "Disinfectants: the whats and wherefores?".

PMID- 7715671
TI  - A situation analysis in nursing education. Part two: Description of probable
      future.

PMID- 7715672
TI  - [A holistic approach to depression].
AB  - An holistic approach is needed in nursing those suffering from depression.
      Because depression is multidimensional in nature, someone who suffers from
      depression is nursed multidimensionally within a whole person approach. The
      nursing process is used as a goal directed method. An holistic approach can
      provide short-term as well as long-term support to someone suffering from
      depression to help to mobilise their own resources for the maintenance,
      restoration and promotion of mental health and create the possibility that they
      realise their optimum potential.

PMID- 7715674
TI  - Acute leukaemia in children.

PMID- 7715673
TI  - Simulation can be fun.

PMID- 7715675
TI  - Are professional associations a stabilising economic force?

PMID- 7715676
TI  - Mapping the AIDS pandemic: geographical progression of HIV in South Africa 1990
      93.

PMID- 7715677
TI  - Disinfectants: the whats and wherefores?

PMID- 7715679
TI  - Basic issues in clinical nursing research.

PMID- 7715678
TI  - [Independent practice?].
AB  - The concept of the nurse as an independent practitioner may be ambiguous and
      misleading. Even in recent nursing publications the concepts of dependence,
      interdependence and independence were used to describe the practice of the nurse.
      This however is not logical or justifiable. The aim of this article is to
      describe the nurse as an independent practitioner who functions as a member of
      the health team within the legal-ethical framework of nursing.

PMID- 7715680
TI  - Blueprint for bombing out!

PMID- 7715681
TI  - Primary health care goals. Compiled by the Sub-committee: Primary Health Care
      Women United in Health.

PMID- 7715682
TI  - Visit of Britain's nursing council registrar.

PMID- 7715683
TI  - Current nursing perspectives in haematology.

PMID- 7715685
TI  - Congress turns spotlight on US drug approval agency.

PMID- 7715684
TI  - Russian genome project.

PMID- 7715686
TI  - London gets funds to restructure its medical colleges.

PMID- 7715687
TI  - MITI drops headlights for gene sequencing.

PMID- 7715688
TI  - Karl Popper.

PMID- 7715689
TI  - Cold war against the Vatican?

PMID- 7715690
TI  - Cold war against the Vatican?

PMID- 7715691
TI  - Cold war against the Vatican?

PMID- 7715692
TI  - Marcus Marci.

PMID- 7715693
TI  - Virology institute changes direction.

PMID- 7715695
TI  - Buried dry ice on Mars.

PMID- 7715694
TI  - Muscle. Flight and phosphorylation.

PMID- 7715696
TI  - Enzyme memory. What is remembered and why?

PMID- 7715697
TI  - Joseph Needham (1900-95).

PMID- 7715698
TI  - Acid-base physiology. Bicarbonate briefly CO2-free.

PMID- 7715699
TI  - Unexpected mutagen in fish.

PMID- 7715700
TI  - Diabetes genes--mutatis mutandis.

PMID- 7715701
TI  - Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos.
AB  - Glycogen synthase kinase 3 (GSK-3) is homologous to the product of the Drosophila
      gene shaggy (zeste-white 3), which is required for signalling by wingless during
      Drosophila development. To test whether GSK-3 is also involved in vertebrate
      pattern formation, its role was investigated during early Xenopus development. It
      was found that dominant-negative GSK-3 mutants induced dorsal differentiation,
      whereas wild-type GSK-3 induced ventralization. These results indicate that GSK-3
      is required for ventral differentiation, and suggest that dorsal differentiation
      may involve the suppression of GSK-3 activity by a wingless/wnt-related signal.

PMID- 7715702
TI  - Out-of-equilibrium CO2/HCO3- solutions and their use in characterizing a new
      K/HCO3 cotransporter.
AB  - In typical physiological solutions, CO2 is in equilibrium with HCO3- and H+ (CO2
      + H2O<==>HCO3- +H+). Because one cannot independently alter CO2 and HCO3-
      concentrations and pH, it is impossible to distinguish between the effects of CO2
      and HCO3- on physiological processes. Here we describe a continuous-flow, rapid
      mixing approach for generating out-of-equilibrium CO2/HCO3- solutions with a
      physiological pH and CO2 (but little HCO3-), or pH and HCO3- (but little CO2). We
      have exploited these out-of-equilibrium solutions to introduce HCO3- exclusively
      to either the outside or inside of a squid giant axon, and verify the presence of
      a new K/HCO3 cotransporter. The out-of-equilibrium approach could be useful in a
      variety of applications for independently controlling CO2 and HCO3-
      concentrations and pH.

PMID- 7715703
TI  - Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines
      are required for mouse fetal development.
AB  - Tyrosine hydroxylase catalyses the initial, rate-limiting step in the
      catecholamine biosynthetic pathway. Catecholamines, which include dopamine,
      noradrenaline, and adrenaline, are important neurotransmitters and hormones that
      regulate visceral functions, motor coordination and arousal in adults. The gene
      encoding tyrosine hydroxylase becomes transcriptionally active in developing
      neuroblasts during mid-gestation of rodent embryos, before the onset of
      neurotransmission. Here we show that inactivation of both tyrosine hydroxylase
      alleles results in mid-gestational lethality: about 90% of mutant embryos die
      between embryonic days 11.5 and 15.5, apparently of cardiovascular failure.
      Administration of L-DOPA (dihydroxyphenylalanine), the product of the tyrosine
      hydroxylase reaction, to pregnant females results in complete rescue of mutant
      mice in utero. Without further treatment, however, they die before weaning. We
      conclude that catecholamines are essential for mouse fetal development and
      postnatal survival.

PMID- 7715704
TI  - Noradrenaline is essential for mouse fetal development.
AB  - Catecholamines such as noradrenaline and adrenaline have been implicated in
      numerous physiological processes but, although catecholamine synthesis begins at
      mid-gestation, previous studies have provided little evidence for any role in
      early development. Furthermore, there are several case reports of humans with
      noradrenaline deficiency. To investigate this, we use gene targeting to produce
      mice lacking dopamine beta-hydroxylase and therefore unable to synthesize
      noradrenaline or adrenaline. We report here that in heterozygous mothers, most
      homozygous embryos died in utero, and only about 5% reached adulthood. Survival
      probably depends on catecholamine transfer across the placenta because, in
      homozygous mothers, all embryos die in utero. Mortality was due to lack of
      noradrenaline in utero because it could be prevented by treatment with
      dihydroxyphenylserine, a precursor that can be converted to noradrenaline in the
      absence of dopamine beta-hydroxylase. Mutant embryos had a histological phenotype
      similar to that of embryos deficient in tyrosine hydroxylase, suggesting that
      death might be due to cardiovascular failure.

PMID- 7715705
TI  - Activation of microglial cells by beta-amyloid protein and interferon-gamma.
AB  - Alzheimer's disease is the most common cause of progressive intellectual failure.
      The lesions that develop, called senile plaques, are extracellular deposits
      principally composed of insoluble aggregates of beta-amyloid protein (A beta),
      infiltrated by reactive microglia and astrocytes. Although A beta, and a portion
      of it, the fragment 25-35 (A beta (25-35)), have been shown to exert a direct
      toxic effect on neurons, the role of microglia in such neuronal injury remains
      unclear. Here we report a synergistic effect between A beta and interferon-gamma
      (IFN-gamma) in triggering the production of reactive nitrogen intermediates and
      tumour-necrosis factor-alpha (TNF-alpha) from microglia. Furthermore, using co
      culture experiments, we show that activation of microglia with IFN-gamma and A
      beta leads to neuronal cell injury in vitro. These findings suggest that A beta
      and IFN-gamma activate microglia to produce reactive nitrogen intermediates and
      TNF-alpha, and this may have a role in the pathogenesis of neuronal degeneration
      observed in ageing and Alzheimer's disease.

PMID- 7715707
TI  - A TBP-TAF complex required for transcription of human snRNA genes by RNA
      polymerase II and III.
AB  - The TATA-box-binding protein TBP exists in the cell complexed with different sets
      of TBP-associated factors (TAFs). In general, each of these TBP-TAF complexes is
      dedicated to transcription by a single RNA polymerase. Thus, SL1, TFIID and
      TFIIIB are required for transcription by polymerases I, II and III, respectively.
      Here we characterize a fourth TBP-TAF complex called SNAPc. Unlike the other TBP
      TAF complexes, SNAPc is implicated in transcription by two types of polymerases;
      it is required for transcription of both the RNA polymerase II and III small
      nuclear RNA genes and binds specifically to the proximal sequence element PSE, a
      non-TATA-box basal promoter element common to these two types of genes. In
      addition to TBP, SNAPc is composed of at least three TAFs, SNAP43, SNAP45 and
      SNAP50. The predicted amino-acid sequence of SNAP43 reveals that it corresponds
      to a new protein.

PMID- 7715706
TI  - Impairment of muscle function caused by mutations of phosphorylation sites in
      myosin regulatory light chain.
AB  - Myosin regulatory light chain is phosphorylated by myosin light chain kinase at
      conserved serine and threonine residues in a number of species. Phosphorylation
      of myosin regulatory light chain regulates smooth muscle contraction, but appears
      to have a modulatory role in striated muscle contraction. We assessed the in vivo
      role of myosin regulatory light chain phosphorylation in the striated muscles of
      Drosophila melanogaster by substituting alanine at each or both conserved myosin
      light chain kinase-dependent phosphorylation sites, serine 66 and serine 67. We
      report here that myosin light chain kinase-dependent phosphorylation is not
      required for myofibrillogenesis or for the development of maximal isometric force
      in indirect flight muscles. However, mutants with substitutions at the major
      phosphorylation site (serine 66) or with the double substitutions had reduced
      power output in isolated flight muscle fibres and reduced flight ability, showing
      that myosin regulatory light chain phosphorylation is a key determinant of the
      stretch activation response in Drosophila.

PMID- 7715708
TI  - Basal promoter elements as a selective determinant of transcriptional activator
      function.
AB  - In eukaryotes, activation of transcription involves an interplay between
      activators bound to cis-regulatory elements and factors bound to basal elements
      near the start site of transcription. The basal elements, for example the TATA
      box or proximal sequence element (PSE) of small nuclear RNA (snRNA) promoters,
      nucleate the assembly of basal transcription complexes, components of which
      interact with activators. Although one basal transcription complex can interact
      with many activators, it is unclear whether different basal transcription
      complexes can direct different responses to particular activators. We show here
      that changing the arrangement of basal elements can alter the response to
      transcriptional activation domains. Indeed, in the human U6 snRNA promoter, point
      mutation of either a TATA box or PSE results in diametrically opposed responses
      to VP16- and Sp1-derived activation domains. These basal elements can even
      discriminate small changes in an activation domain. Thus the arrangement of basal
      promoter elements provides a mechanism for differential regulation of
      transcription.

PMID- 7715710
TI  - End of the road for poliomyelitis?
AB  - There seems a real prospect that one of the infectious scourges of the past half
      century will not persist much beyond the present century, but polio will be only
      the second infection of human beings to be eradicated. Many more remain.

PMID- 7715709
TI  - RNA polymerase II C-terminal domain required for enhancer-driven transcription.
AB  - The RNA polymerase II carboxy-terminal domain (CTD) consists of tandem repeats of
      the sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser. The CTD may participate in activated
      transcription through interaction with a high-molecular-weight mediator complex.
      Such a role would be consistent with observations that some genes are
      preferentially sensitive to CTD mutations. Here we investigate the function of
      the mouse RNA polymerase CTD in enhancer-driven transcription. Transcription by
      alpha-amanitin-resistant CTD-deletion mutants was tested by transient
      transfection of tissue culture cells in the presence of alpha-amanitin in order
      to inhibit endogenous RNA polymerase II. Removal of most of the CTD abolishes
      transcriptional activation by all enhancers tested, whereas transcription from
      promoters driven by Sp1, a factor that typically activates housekeeping genes
      from positions proximal to the initiation sites, is not affected. These findings
      show that the CTD is essential in mediating 'enhancer'-type activation of
      mammalian transcription.

PMID- 7715713
TI  - DNA evidence called to check 'holy tears'.

PMID- 7715714
TI  - Earth-bound rules threaten quest for extraterrestrial life.

PMID- 7715712
TI  - Patent convention 'needs new protocol on moral issues'.

PMID- 7715711
TI  - Nature ownership to change hands.

PMID- 7715715
TI  - NIH drops reasonable pricing clause.

PMID- 7715716
TI  - Warnings raised over black-market vaccines.

PMID- 7715717
TI  - Apoptosis.

PMID- 7715718
TI  - Research involving animals.

PMID- 7715719
TI  - Adaptive events.

PMID- 7715720
TI  - Molecular medicine in development.

PMID- 7715721
TI  - Developmental neurobiology. A real gene for reeler.

PMID- 7715722
TI  - Vertebrate embryo handedness.

PMID- 7715723
TI  - The structure of trp RNA-binding attenuation protein.
AB  - The crystal structure of the trp RNA-binding attenuation protein of Bacclius
      subtilis solved at 1.8 A resolution reveals a novel structural arrangement in
      which the eleven subunits are stabilized through eleven intersubunit beta-sheets
      to form a beta-wheel with a large central hole. The nature of the binding of L
      tryptophan in clefts between adjacent beta-sheets in the beta-wheel suggests that
      this binding induces conformational changes in the flexible residues 25-33 and 49
      52. It is argued that upon binding, the messenger RNA target forms a matching
      circle in which eleven U/GAG repeats are bound to the surface of the protein
      ondecamer modified by the binding of L-tryptophan.

PMID- 7715724
TI  - Waves from the collisions of comet Shoemaker-Levy 9 with Jupiter.
AB  - Observations of the collisions of the fragments of comet Shoemaker-Levy 9 with
      Jupiter provided an unprecedented opportunity to probe the depths of the planet's
      atmosphere. Images taken by the Hubble Space Telescope revealed circular rings
      surrounding five of the impact sites. The rings were observed for up to 2.5 hours
      after the impacts and spread at a constant velocity of 450 m s-1. There are three
      types of disturbance that might explain these observations: acoustic waves
      trapped at the tropopause temperature minimum, gravity waves propagating
      vertically and horizontally in the stratosphere, and gravity waves trapped in a
      stable layer which acts as a horizontal waveguide and is located within the
      hypothesized tropospheric water cloud. Here we show that only the last of these
      phenomena can match the speed and relative amplitude of the observed waves, with
      the requirement that the impacts were deep and the stability of the trapping
      layer is large. The origin of the stable layer is still uncertain, but if it is
      produced by moist convection in the water cloud, then the ratio of oxygen to
      hydrogen on Jupiter must be surprisingly large--approximately ten times that on
      the Sun.

PMID- 7715725
TI  - Early functional neural networks in the developing retina.
AB  - In the adult mammalian retina, the principal direction of information flow is
      along a vertical pathway from photoreceptors to retinal interneurons to ganglion
      cells, the output neurons of the retina. We report here, however, that initially
      in development, at a time when the photoreceptors are not yet even present, there
      are already functionally defined networks within the retina. These networks are
      spontaneously active rather than visually driven, and they involve horizontal
      rather than vertical pathways. By means of optical recording using the calcium
      sensitive dye Fura-2, we have found that sets of retinal ganglion cells and
      amacrine cells, a type of retinal interneuron, undergo synchronized oscillations
      in intracellular calcium concentration. These oscillations are highly correlated
      among subgroups of neighbouring cells, and spread in a wave-like fashion
      tangentially across the retina. Thus, in development of retinal circuitry, the
      initial patterning of neuronal function occurs in the horizontal domain before
      the adult pattern of vertical information transfer emerges.

PMID- 7715726
TI  - A protein related to extracellular matrix proteins deleted in the mouse mutant
      reeler.
AB  - The autosomal recessive mouse mutation reeler leads to impaired motor
      coordination, tremors and ataxia. Neurons in affected mice fail to reach their
      correct locations in the developing brain, disrupting the organization of the
      cerebellar and cerebral cortices and other laminated regions. Here we use a
      previously characterized reeler allele (rl(tg)) to close a gene, reelin, deleted
      in two reeler alleles. Normal but not mutant mice express reelin in embryonic and
      postnatal neurons during periods of neuronal migration. The encoded protein
      resembles extracellular matrix proteins involved in cell adhesion. The reeler
      phenotype thus seems to reflect a failure of early events associated with brain
      lamination which are normally controlled by reelin.

PMID- 7715727
TI  - Transformation of axial skeleton due to overexpression of bmi-1 in transgenic
      mice.
AB  - The oncogene bmi-1, which was originally found to be involved in B- and T-cell
      lymphoma formation encodes a protein with a domain of homology to the Drosophila
      protein Posterior sex combs (Psc) and its relative Suppressor 2 of Zeste (Su(z)2)
      (refs 4 and 5). Psc is a member of the Polycomb-group gene family, which is
      required to maintain the repression of homeotic genes that regulate the
      identities of Drosophila segments. The possibility that bmi-1 may play a similar
      role in vertebrates was suggested by our previous finding that mice lacking the
      bmi-1 gene show posterior transformations of the axial skeleton. Here we report
      that transgenic mice overexpressing Bmi-1 protein show the opposite phenotype,
      namely a dose-dependent anterior transformation of vertebral identity. The
      anterior expression boundary of the Hoxc-5 gene is shifted in the posterior
      direction, indicating that Bmi-1 is involved in the repression of Hox genes. We
      propose that Bmi-1 is a member of a vertebrate Polycomb complex that regulates
      segmental identity by repressing Hox genes throughout development.

PMID- 7715728
TI  - The barley Hooded mutation caused by a duplication in a homeobox gene intron.
AB  - In barley (Hordeum vulgare L.) the unit of inflorescence is the spikelet, which
      bears a fertile bract, the lemma, and the floret consisting of palea, two
      lodicules, three stamens and the pistil. The Hooded mutation causes the
      appearance of an extra flower of inverse polarity on the lemma. This phenotype is
      governed by the single dominant genetic locus K3. Here we show that the homeobox
      gene Knox3 represents this locus. Ectopic Knox3 gene expression in the primordium
      of the extra floret is caused by a 305-base pair duplication in intron 4, and
      phenocopies of the mutation are obtained in the heterologous tobacco system by
      Knox3 overexpression. It is concluded that homeotic genes of the Knox gene family
      are involved in floral evocation. Furthermore, the study of polarity of
      reproductive organs in K and related mutants can now focus on homeobox genes.

PMID- 7715729
TI  - Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K.
AB  - A number of DNA viruses carry apoptosis-inhibiting genes which enable the virus
      to escape from the host response. The adenovirus E1B 19K protein can inhibit
      apoptosis induced by E1A, tumour-necrosis factor-alpha, FAS antigen and nerve
      growth factor deprivation. The molecular basis of this inhibition remains poorly
      understood, but the fact that protection is seen in the absence of other viral
      proteins suggests that E1B 19K targets cellular proteins. We report here the
      identification of three cellular proteins that bind E1B 19K. One of these is a
      new member of the bcl-2 family, which we have called bak (for bcl-2 homologous
      antagonist/killer). This protein, which is expressed in a wide variety of cell
      types, binds to E1B 19K and to the Bcl-2 homologue Bcl-XL (ref. 17) in yeast. In
      addition, overexpression of bak in sympathetic neurons deprived of nerve growth
      factor accelerates apoptosis and blocks the protective effect of co-injected E1B
      19K.

PMID- 7715730
TI  - Induction of apoptosis by the Bcl-2 homologue Bak.
AB  - Cells are eliminated in a variety of physiological settings by apoptosis, a
      genetically encoded process of cellular suicide. Apoptosis comprises an intrinsic
      cellular defence against tumorigenesis, which, when suppressed, may contribute to
      the development of malignancies. The bcl-2 oncogene, which is activated in
      follicular lymphomas, functions as a potent suppressor of apoptosis under diverse
      conditions. Here we describe the complementary DNA cloning and functional
      analysis of a new Bcl-2 homologue, Bak, which promotes cell death and counteracts
      the protection from apoptosis provided by Bcl-2. Moreover, enforced expression of
      Bak induces rapid and extensive apoptosis of serum-deprived fibroblasts. This
      raises the possibility that Bak is directly involved in activating the cell death
      machinery.

PMID- 7715731
TI  - Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak.
AB  - Members of the Bcl-2 family of proteins are characterized by their ability to
      modulate cell death. Bcl-2 and some of its homologues inhibit apoptosis, whereas
      other family members, such as Bax, will accelerate apoptosis under certain
      conditions. Here we describe the identification and characterization of a
      complementary DNA that encodes a previously unknown Bcl-2 homologue designated
      Bak. Like Bax, the bak gene product primarily enhances apoptotic cell death
      following an appropriate stimulus. Unlike Bax, however, Bak can inhibit cell
      death in an Epstein-Barr-virus-transformed cell line. The widespread tissue
      distribution of Bak messenger RNA, including those containing long-lived,
      terminally differentiated cell types, suggests that cell-death-inducing activity
      is broadly distributed, and that tissue-specific modulation of apoptosis is
      controlled primarily by regulation of molecules that inhibit apoptosis.

PMID- 7715733
TI  - German Society for Experimental and Clinical Pharmacology and Toxicology.
      Abstracts of the 6th winter meeting. 1-3 December 1994, Hannover.

PMID- 7715732
TI  - High-resolution structure of a DNA helix forming (C.G)*G base triplets.
AB  - Triple helices result from interaction between single- and double-stranded
      nucleic acids. Their formation is a possible mechanism for recombination of
      homologous gene sequences in nature and provides, inter alia, a basis for
      artificial control of gene activity. Triple-helix motifs have been extensively
      studied by a variety of techniques, but few high-resolution structural data are
      available. The only triplet structures characterized so far by X-ray diffraction
      were in protein-DNA complexes studied at about 3 A resolution. We report here the
      X-ray analysis of a DNA nonamer, d(GCGAATTCG), to a resolution of 2.05 A, in
      which the extended crystal structure contains (C.G)*G triplets as a fragment of
      triple helix. The guanosine-containing chains are in a parallel orientation. This
      arrangement is a necessary feature of models for homologous recombination which
      results ultimately in replacement of one length of DNA by another of similar
      sequence. The present-structure agrees with many published predictions of triplex
      organization, and provides an accurate representation of an element that allows
      sequence-specific association between single- and double-stranded nucleic acids.

PMID- 7715734
TI  - Agmatine recognizes alpha 2-adrenoceptor binding sites but neither activates nor
      inhibits alpha 2-adrenoceptors.
AB  - It has been suggested that agmatine (decarboxylated arginine) is an endogenous
      clonidine-displacing substance (CDS) which recognizes alpha 2-adrenoceptor and
      non-adrenoceptor, imidazoline binding sites. We have examined the effect of
      agmatine at alpha 2-adrenoceptor binding sites and pre- and postjunctional alpha
      2-adrenoceptors. Agmatine produced a concentration-dependent inhibition of 1
      nmol/l 3H-clonidine binding to both rat (pKi-5.10 +/- 0.05) and bovine (pKi-4.77
      +/- 0.38) cerebral cortex membranes. However, agmatine (0.1-100 microM) failed to
      activate pre-junctional alpha 2-adrenoceptors regulating transmitter release in
      the guinea-pig isolated ileum and rat isolated vas deferens, nor did it activate
      postjunctional alpha 2-adrenoceptors of the porcine isolated palmar lateral vein
      which mediate contraction or inhibition of forskolin-stimulated cyclic AMP
      formation. High concentrations of agmatine (10-30-fold the pKi at alpha 2
      adrenoceptor binding sites) failed to influence alpha 2-adrenoceptor activation
      by either clonidine or UK-14304 (5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline
      bitartrate) in any of the peripheral preparations examined. Moreover, even in a
      preparation where an interaction with alpha 2-adrenoceptor binding sites on cell
      membranes can be demonstrated, the rat cerebral cortex, agmatine failed to
      inhibit forskolin-stimulated cyclic AMP in the intact tissue or affect the
      inhibition produced by the selective alpha 2-adrenoceptor agonist UK-14304.
      Agmatine was also devoid of agonist activity in two preparations, the rat
      isolated thoracic aorta and the rat isolated gastric fundus, in which CDS has
      been reported to produce non-adrenoceptor effects. Thus, we have confirmed that
      agmatine recognizes alpha 2-adrenoceptor binding sites and, therefore, is a
      CDS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715735
TI  - Two relaxation-mediating P2-purinoceptors in guinea-pig taenia caeci.
AB  - 2-Methylthio ATP, noradrenaline, adenosine 5'-O-(2-thiodiphosphate) (ADP beta S),
      alpha, beta-methylene ATP, ATP and adenosine caused relaxation of guinea-pig
      isolated taenia caeci precontracted by carbachol, with potency decreasing in the
      order indicated. 4,4'-Diisothiocyanatostilbene-2,2'-disulphonate (DIDS) 10, 32
      and 100 microM shifted the concentration-response curve of alpha, beta-methylene
      ATP increasingly to the right, by the factor 141 at DIDS 100 microM.
      Concentration-response curves of the other agonists were not shifted to the right
      by DIDS 100 microM, except for the curve of ADP beta S which was shifted by the
      factor 2.4. The relaxation produced by 2-methylthio ATP faded rapidly. When the
      fade was complete, further addition of 2-methylthio ATP or ATP did not elicit
      relaxation, whereas the relaxant effect of alpha, beta-methylene ATP was
      unchanged. The results indicate that there are at least two relaxation-mediating
      P2-purinoceptors in guinea-pig taenia caeci, the P2Y-purinoceptor which is
      relatively insensitive to DIDS and a distinct receptor for alpha, beta-methylene
      ATP which is very sensitive to DIDS.

PMID- 7715736
TI  - Evidence for the presence of a non-catecholamine, clonidine-displacing substance
      in crude, methanolic extracts of bovine brain and lung.
AB  - In the present study we have prepared crude, methanolic extracts of bovine lung
      and bovine brain and, using radioligand binding assays in conjunction with a
      number of simple chromatographic techniques, provided evidence for the presence
      of a non-catecholamine 'clonidine-displacing substance' (CDS). The level of CDS
      in lung extracts (9 units/g wet weight n = 11) is approximately 3 times that in
      the brain extracts. Furthermore, the effect of the crude, methanolic extracts are
      selective for non-adrenoceptor, imidazoline (labelled by [3H]-idazoxan) and alpha
      2-adrenoceptor binding sites (labelled by [3H]-clonidine); both extracts are 5-10
      fold more potent displacers of ligand binding to alpha 2-adrenoceptors compared
      with binding to opiate receptors (labelled by [3H]-etorphine) and practically
      inactive against alpha 1-adrenoceptor and muscarinic binding sites (labelled by
      [3H]-prazosin and [3H]-quinuclidinyl benzilate, respectively). With the exception
      of the non-adrenoceptor, imidazoline binding assay, which used rat kidney
      membranes labelled by [3H]-idazoxan in the presence of the alpha 2-adrenoceptor
      antagonist RS-15385-197, all radioreceptor assays involved bovine cerebral cortex
      membranes. Although the extracts contain catecholamines (brain only), histamine
      (lung only) and monovalent cations (both), which have the potential to interfere
      with the radioligand binding assays, their concentrations were too low to account
      for the effects observed. Preliminary attempts at purification of the extracts
      revealed that CDS activities from the two tissues are similar, i.e., practically
      insoluble in organic solvents at room temperature, not affected by either Sep-Pak
      C18 column or anion exchange resins but retained (along with the monovalent
      cations) by cation exchange resin. However, following chromatographic separation
      on a Biogel P2 column, the CDS-containing eluates are cation-free and exhibit
      qualitatively similar elution profiles. Future experiments will involve further
      purification of 'clonidine-displacing substance' to characterize its interaction
      with alpha 2-adrenoceptor binding sites in greater detail and establish whether
      it has biological activity consistent with the properties implied by its effects
      in radioligand binding assays.

PMID- 7715737
TI  - Pharmacological profiles of a novel alpha 1-adrenoceptor agonist, PNO-49B, at
      alpha 1-adrenoceptor subtypes.
AB  - The effects of a newly synthesized compound, PNO-49B, (R)-(-)-3'-(2-amino-1
      hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, on alpha 1
      adrenoceptor subtypes were examined in various tissues in which the following
      distribution of alpha 1-adrenoceptor subtypes has been suggested: dog carotid
      artery (alpha 1B), dog mesenteric artery (alpha 1N), rabbit thoracic aorta (alpha
      1B + alpha 1L), rat liver (alpha 1B), rat vas deferens (alpha 1A + alpha 1L), rat
      cerebral cortex (alpha 1A + alpha 1B) and rat thoracic aorta (controversial
      subtype). PNO-49B (0.1-100 microM) produced concentration-dependent contractions
      in dog mesenteric artery, rabbit thoracic aorta, rat thoracic aorta and rat vas
      deferens; and the maximal amplitudes of contraction were almost the same as or
      slightly less than those of noradrenaline. By contrast, the maximal response to
      PNO-49B in dog carotid artery was markedly smaller than the response to
      noradrenaline. In rabbit thoracic aorta, the contractile response to PNO-49B was
      not affected by inactivation of the alpha 1B subtype with chloroethylclonidine
      (CEC), although the response to noradrenaline was attenuated by that treatment.
      The dissociation constants (KA) of PNO-49B were not different among the rat
      thoracic aorta, dog carotid and mesenteric arteries and rabbit thoracic aorta
      (CEC-pretreated). The contractile responses to PNO-49B were inhibited
      competitively by prazosin, HV723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2
      methoxyphenoxy)-ethyl)- amino(propyl)benzeneacetonitrile fumarate) and by WB4101
      (2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4- benzodioxane).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7715738
TI  - Chronic muscarinic cholinoceptor stimulation increases adenylyl cyclase
      responsiveness in rat cardiomyocytes by a decrease in the level of inhibitory G
      protein alpha-subunits.
AB  - Exposure of neonatal rat cardiomyocytes for 3 days to the muscarinic
      cholinoceptor agonist carbachol led to a concentration-dependent increase in
      adenylyl cyclase stimulation by the beta-adrenoceptor agonist isoproterenol by up
      to 115% (at 1 mmol/l carbachol). In addition, direct adenylyl cyclase stimulation
      by forskolin was increased in carbachol (1 mmol/l)-treated cells by 32%.
      Pretreatment of the rat cardiomyocytes with pertussis toxin, which enhances
      adenylyl cyclase activity by a functional inactivation of the inhibitory G
      protein (Gi), was performed to investigate the possible role of Gi-proteins in
      carbachol-induced sensitization of adenylyl cyclase stimulation. After
      pretreatment of the cells with pertussis toxin, the carbachol-mediated increase
      in forskolin-stimulated adenylyl cyclase activity was lost and the carbachol
      mediated increase in beta-adrenoceptor-stimulated adenylyl cyclase activity was
      attenuated. Labelling of the 40 kDa pertussis toxin substrates in cardiomyocyte
      membranes was decreased by carbachol in a concentration-dependent manner by up to
      34% (at 1 mmol/l carbachol). The number and affinity of beta 1-adrenoceptors was
      unaltered following the chronic carbachol treatment. The specific protein
      synthesis inhibitor Pseudomonas exotoxin A was used to study whether the
      carbachol-induced decrease in the level of pertussis toxin-sensitive G-proteins
      and increase in adenylyl cyclase activity depend on de-novo protein synthesis.
      Pseudomonas exotoxin A inhibits peptide chain elongation by ADP-ribosylating
      elongation factor 2. Treatment of the cells with 1 ng/ml Pseudomonas exotoxin A
      for 3 days led to a reduction in the subsequent ADP-ribosylation of elongation
      factor 2 in the cytosol of the heart muscle cells by 57%.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7715740
TI  - Evidence for a direct interaction of thapsigargin with voltage-dependent Ca2+
      channel.
AB  - The effect of thapsigargin, an inhibitor of the sarco-endoplasmic reticulum
      Ca(2+)-ATPase, on voltage-dependent Ca2+ channels has been investigated in the
      A7r5 cell line and in membrane preparations from rat aorta, heart and brain.
      Patch-clamp technique showed that, at micromolar concentrations, thapsigargin
      inhibited the L-type Ca2+ channel current in A7r5 cells. It depressed the current
      at all voltages without change in the steady state inactivation curve. The rates
      of inactivation of the Ca2+ current were highly variable among the cells
      suggesting that more than one component of L-type Ca2+ current coexist in A7r5
      cells, differing in the kinetics of inactivation. Thapsigargin appeared to be
      more potent on the slower-inactivating Ca2+ current than on the faster
      inactivating one. In the same range of concentrations, thapsigargin inhibited the
      specific binding of 3H(+)-isradipine in intact cells while 45Ca2+ uptake in
      intracellular stores of skinned cells was inhibited at nanomolar concentrations.
      The equilibrium dissociation constant of 3H(+)-isradipine was increased in the
      presence of thapsigargin as a result of an increase of the dissociation rate
      constant indicating that the inhibitory effect of the antagonist cannot be
      attributed to a simple competitive interaction with the dihydropyridine binding
      site. Maximum binding capacity was unaffected. A similar pattern of inhibition of
      3H(+)-isradipine binding was observed in membrane preparations from rat aorta,
      heart and brain. Those results indicate that, at micromolar concentrations,
      thapsigargin inhibits the voltage-dependent Ca2+ current by a direct interaction
      with the L-type Ca2+ channels.

PMID- 7715739
TI  - 5-Hydroxytryptamine 5-HT1B receptors inhibiting cyclic AMP accumulation in rat
      renal mesangial cells.
AB  - A clonal cell line derived from rat renal mesangial cells was shown to express
      endogenous 5-hydroxytryptamine (serotonin, 5-HT) receptors that mediate
      inhibition of cyclic AMP accumulation. These receptors were characterized as
      being of the 5-HT1B receptor subtype. 5-HT1 receptor agonists inhibited forskolin
      stimulated cyclic AMP accumulation in rat renal mesangial cells (60-70% maximal
      inhibition) with the following rank order of potency (mean pEC50 values +/- SEM,
      n > or = 3): ergotamine (9.58 +/- 0.51) > RU 24969 (8.67 +/- 0.23) > or = 5-CT
      (8.42 +/- 0.06) > or = CP 93129 (8.15 +/- 0.27) > 5-HT (7.75 +/- 0.11) >
      sumatriptan (6.29 +/- 0.30) > 8-OH-DPAT (4.32 +/- 0.15). 5-HT2 and 5-HT4 receptor
      agonists were without effect. 5-HT-induced inhibition of cyclic AMP accumulation
      was abolished by a pre-treatment of the cells with pertussis toxin. (
      )Propranolol was a partial agonist (27% maximal inhibition, pEC50 7.19 +/- 0.24,
      n = 3); when used as an antagonist at 1 microM, it shifted the concentration
      response curve of 5-HT to the right (pKB 7.22 +/- 0.35, n = 3). Methiothepin was
      a competitive antagonist of 5-HT (pA2 8.04 +/- 0.10, Schild slope 0.87 +/- 0.21,
      n = 3). Rauwolscine (10 microM) had no antagonist activity. There was a
      significant correlation (r = 0.98, P = 0.0001) between the cyclic AMP data
      obtained in rat mesangial cells and 5-HT1B binding data reported in rat brain
      cortex. The same pattern of responses was observed in early passages of primary
      cultures of rat mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715741
TI  - Prostanoid receptors of the EP3 subtype mediate the inhibitory effect of
      prostaglandin E2 on noradrenaline release in the mouse brain cortex.
AB  - Mouse or rat brain cortex slices were preincubated with 3H-noradrenaline and
      superfused with physiological salt solution containing desipramine. We studied
      the effects of prostaglandin E2 (PGE2), prostaglandin D2 (PGD2) and related drugs
      on the electrically evoked (50 mA, 2 ms, 0.3 Hz) tritium overflow. PGE2 inhibited
      the electrically evoked tritium overflow from mouse brain cortex slices; the
      maximum effect of PGE2 (79%) was attenuated by the alpha 2-adrenoceptor agonist
      talipexole (to 52%) and enhanced by the alpha 2-adrenoceptor antagonist
      rauwolscine (to 92%). Rauwolscine was added to the superfusion medium in all
      subsequent experiments. The effect of PGE2 was readily reversible upon withdrawal
      from the medium and remained constant upon prolonged exposure of the tissue to
      the prostanoid. Studies with EP receptor agonists, mimicking the inhibitory
      effect of PGE2, showed the following potencies (pIC50); sulprostone (8.22);
      misoprostol (8.00); PGE2 (7.74); PGE1 (7.61); iloprost (5.86). The concentration
      response curve of PGE2 was marginally shifted to the right by the EP1 receptor
      antagonist AH 6809 (6-isopropoxy-9-oxoxanthene-2- carboxylic acid; apparent pA2
      3.97) and by the TP receptor antagonist vapiprost (4.50). AH 6809, by itself, did
      not affect the evoked overflow whereas vapiprost increased it. PGD2 inhibited the
      evoked overflow at high concentrations (pIC50 4.90); this effect was not altered
      by the DP receptor antagonist BW A868C (3-benzyl-5-(6-carboxyhexyl)-1-(2
      cyclohexyl-2- hydroxyethylamino)hydantoin), which, by itself, did not affect the
      evoked overflow. Indometacin slightly increased the evoked overflow and tended to
      increase the inhibitory effect of PGE2. PGE2 inhibited the electrically evoked
      tritium overflow also in rat brain cortex slices.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7715742
TI  - Okadaic acid modulates exocytotic and transporter-dependent release of dopamine
      in bovine retina in vitro.
AB  - Bovine retinas were isolated for the study of the modulation of exocytotic and
      transporter-dependent release of dopamine (DA) in vitro. Endogenous DA was
      measured in the medium using HPLC with electrochemical detection under successive
      incubations with transfers in fresh medium every 30 min. As expected, potassium
      caused a calcium-dependent exocytotic liberation of DA. Amphetamine or tyramine
      induced a calcium-independent release by reversing DA transport across the plasma
      membrane. Okadaic acid, a specific inhibitor of phosphatases 1 and 2A, induced a
      slight but significant DA release in the absence of calcium. Furthermore, the
      toxin increased potassium-, amphetamine- or tyramine-induced DA release
      independently of extracellular calcium. In addition, okadaic acid completely
      annulled the ability of a calcium-free extracellular environment to inhibit the
      potassium-induced DA release. Finally, the toxin prevented the time-dependent
      decline in the efficacies of amphetamine or tyramine to release DA. In agreement
      with proposed schemes described for rat striatum, the results of the present
      study confirmed the existence of distinct release modes of DA in bovine retina.
      The results obtained with okadaic acid suggest that phosphatase 1 and/or
      phosphatase 2A constitute part of a direct or indirect mechanism to inhibit both
      exocytotic and transporter-dependent DA release.

PMID- 7715743
TI  - Electrically-evoked release of taurine in the rat vas deferens: evidence for a
      purinoceptor-mediated effect.
AB  - Release of taurine evoked by electrical stimulation (2700 pulses; 5 Hz; 10 mA
      unless stated otherwise) and its dependence on noradrenaline and ATP was studied
      in isolated, perifused rat vas deferens. Outflow of noradrenaline was also
      measured in some experiments. The basal outflow of taurine averaged 3.90 +/- 0.32
      nmol/g tissue per min. Electrical stimulation increased the outflow to about 4
      times basal values. The electrically-evoked overflow averaged 128.0 +/- 11.7
      nmol/g. An increase in current strength to 40 mA increased the evoked overflow by
      about 50%. At either current strength, the evoked overflow of taurine (and
      noradrenaline) was abolished by tetrodotoxin. Ca(2+)-deprivation blocked the
      overflow of taurine elicited by 10 mA and increased the overflow elicited by 40
      mA pulses (but abolished noradrenaline overflow under either condition). Neither
      prazosin nor pretreatment of the rats with reserpine reduced electrically-evoked
      overflow of taurine (although reserpine pretreatment abolished evoked
      noradrenaline overflow). Tyramine (100 mumols/l; 9 min) caused an overflow of
      taurine 36% of that caused by electrical stimulation (but an overflow of
      noradrenaline 3 times higher than that evoked by electrical stimulation).
      Exogenous noradrenaline (9 min) caused a concentration-dependent overflow of
      taurine with a maximal effect at 162 mumol/l, amounting to 33% of the
      electrically-evoked overflow. alpha,beta-Methylene ATP (19 mumols/l) elicited an
      overflow of taurine that faded despite continued exposure to the drug and
      amounted to 62% of the response to electrical stimulation. Thirty minutes after
      the start of application of alpha,beta-methylene ATP, electrically-evoked
      overflow of taurine was greatly reduced. Suramin (100 mumols/l) also reduced
      taurine overflow in response to electrical stimulation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7715744
TI  - Processing of tetanus and botulinum A neurotoxins in isolated chromaffin cells.
AB  - Tetanus and botulinum A neurotoxins were introduced into the cytosol of
      chromaffin cells by means of an electric field in which the plasma membrane is
      forced to form pores of approximately 1 micron at the sites facing the
      electrodes. As demonstrated by electron microscopy, both [125I] and gold-labelled
      tetanus toxin (TeTx) diffuse through these transient openings. Dichain-TeTx, with
      its light chain linked to the heavy chain by means of a disulfide bond, causes
      the block of exocytosis to develop more slowly than does the purified light
      chain. The disulfide bonds, which in both toxins hold the subunits together, were
      cleaved by the intrinsic thioredoxin-reductase system. Single chain TeTx, in
      which the heavy and light chains are interconnected by an additional peptide
      bond, was far less effective than dichain-TeTx at blocking exocytosis, which
      indicates that proteolysis is the rate-limiting step. The toxins were degraded
      further to low-molecular weight fragments which, together with intact toxins and
      subunits, were released by the cells. The intracellular half-life of [125I]
      dichain-TeTx was approximately three days. The number of light-chain molecules
      required to maintain exocytosis block in a single cell, as calculated by two
      different methods, was less than 10. The long duration of tetanus poisoning may
      result from the persistence of intracellular toxin due to scarcity of free
      cytosolic proteases. This may also hold for the slow recovery from botulism.

PMID- 7715746
TI  - Prilocaine elimination by isolated perfused rat lung and liver.
AB  - Prilocaine is assumed to undergo significant elimination by extrahepatic organs
      and to differ in this respect from other commonly used local anaesthetics. In
      order to clarify whether the lung may play an important role as a site of
      elimination of prilocaine, the kinetic parameters were studied in isolated
      perfused rat lungs and were compared to those of isolated livers. Furthermore,
      the structurally related compounds bupivacaine and mepivacaine were also
      investigated in this system. Prilocaine was dispersed into a relatively large
      apparent distribution volume in perfused rat lung (139 ml versus 97 ml in
      controls). In single-pass perfused lungs the observed maximum of concentration
      was decreased by about 60% compared to controls. The mean residence time was
      prolonged by about 40%. These observations suggest that prilocaine is
      substantially retained by rat lung and that this effect occurs particularly
      during first-pass. However, the ability of rat lung to degrade prilocaine was
      relatively low. The clearance values were about 0.3 ml/min equal to about 20% of
      the hepatic capacity calculated per g of tissue. Thus it must be assumed that
      prilocaine is only transiently retained by the lung and will gain systemic
      availability later on. In rat lungs the kinetics of prilocaine elimination were
      not substantially different from those of bupivacaine and mepivacaine (16 and
      12%). These observations do not support the assumption that especially prilocaine
      undergoes extrahepatic elimination.

PMID- 7715745
TI  - Involvement of opioid receptors in N-methyl-D-aspartate-induced arterial
      hypertension in periaqueductal gray matter.
AB  - Arterial hypertension induced by microinjections of N-methyl-D-aspartate (NMDA)
      (2 nmol/rat) into the midbrain periaqueductal gray matter was used to assess the
      involvement of opioid receptors (mu, delta and kappa) in modulating pressor
      periaqueductal gray neurons. Groups (n = 5-8) of urethane-anaesthetised rats
      received, 5 min before NMDA, microinjections of selective opioid receptor
      antagonists in the periaqueductal gray area and arterial blood pressure was
      monitored. Pretreatments with naloxone (5 nmol/rat), a non selective mu receptor
      antagonist, or naltrindole hydrochloride (5 nmol/rat), a selective delta receptor
      antagonist, significantly (P < 0.05) decreased by 31% and 37%, respectively, NMDA
      induced hypertension. The latency for the maximum increase of NMDA-induced
      hypertension was also significantly (P < 0.05) increased with naloxone.
      Pretreatment with nor-binaltorphimine (5 nmol/rat), a selective kappa receptor
      antagonist, only increased the latency of NMDA-induced hypertension. Each opioid
      antagonist failed per se to alter arterial blood pressure. Microinjection of
      morphine (13 nmol/rat), a non selective mu receptor agonist, significantly
      decreased (P < 0.05) by 57.5% NMDA-induced arterial hypertension and this effect
      was antagonised by naloxone. Combined pretreatments in the periaqueductal gray
      area with naloxone and the GABAA antagonist bicuculline (2.5 nmol/rat; 5 min
      before naloxone) antagonised the effect of naloxone on NMDA-induced hypertension.
      In contrast, bicuculline significantly (P < 0.05) potentiated morphine-induced
      decrease of NMDA hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715747
TI  - Pulmonary uptake of bupivacaine in isolated perfused rat lung.
AB  - The ability of rat lung to remove the local anaesthetic drug bupivacaine from the
      blood was studied in isolated organs which were perfused either in an open
      (single-pass mode) or in a closed system (recirculating medium). Isolated
      perfused rat lungs exhibited a very low capacity to metabolize bupivacaine within
      3 h during which the drug circulated continuously through the organ. The
      clearance values differed only by 0.2 ml/min from the control parameters in sham
      perfusions. The calculated extraction ratio was 0.2% and the elimination half
      life was about 210 min. The volume of distribution of bupivacaine was 133 ml
      which remarkably surmounted the reference values obtained for sham perfusions.
      The distribution of bupivacaine into the pulmonary tissue was investigated
      applying the multiple indicator dilution technique to isolated lungs perfused in
      the single-pass mode. The mean elimination time of model compounds for
      distribution into the intravascular space, 14C-insulin, and the total water
      space, 3H-water, were 68 and 75 s at a flow rate of 6 ml/min. The volume of
      distribution was 5.9 ml for inulin and 6.5 ml for water. The mean transit time
      for concomitantly injected bupivacaine was 221 s and the volume of distribution
      was 14.4 ml. The respective parameters of sham perfusions performed without an
      isolated organ were substantially lower, i.e. mean elimination time 50, 50 and 61
      s and distribution volume 4.9, 5.0 and 6.1 ml for inulin, water and
      bupivacaine.2+ f1p4

PMID- 7715748
TI  - [Congenital diseases of neuromuscular transmission: congenital myasthenia
      syndromes].
AB  - The congenital myasthenic syndrome constitute a group of genetic disorders
      affecting neuromuscular transmission. This group includes presynaptic as well as
      postsynaptic defects. In several congenital myasthenic syndromes, it was possible
      to characterize the underlying mechanism by applying modern in vitro
      electrophysiological methods, like single-channel recordings. These genetic
      disorders include defects of acetylcholine release, absence of the endplate
      specific form of acetylcholinesterase, and kinetic abnormalities of the
      acetylcholine receptor. Recently several mutations of the acetylcholine receptor
      have been characterized. Clinical features of these syndromes, diagnostic work
      up, and treatment are described in detail. These diseases present usually within
      the first 2 years of life, however, in some syndromes manifestation during
      adulthood is possible. The clinical spectrum ranges from mild muscle weakness to
      severe disability with lifethreatening episodes. Only some syndromes respond to
      acetylcholinesterase inhibitors. Further elucidation of these syndromes will not
      only lead to improved treatment, but should contribute to our understanding of
      synaptic transmission.

PMID- 7715749
TI  - [Strategies for early admission of stroke patients].
AB  - From March to August 1993 we performed a comprehensive educational campaign about
      stroke and acute stroke therapies to shorten admission delay and to recruit more
      patients for the ECASS trial [8]. We compared the presentation data of all stroke
      patients admitted in a six month preeducational period with data of a six month
      posteducational period. The median admission delay was significantly reduced from
      eight hours in the preeducational to five hours in the posteducational period.
      The number of patients undergoing thrombolytic treatment increased. The following
      factors shortened admission delay: age > 70 years, living in cities, stroke onset
      during daytime, admission by ambulance, stroke in anterior circulation,
      cardiogenic embolic stroke, severe symptoms.

PMID- 7715750
TI  - [Quantitative tilt table study with TCD monitoring. A reliable method for the
      diagnosis of neurocardiogenic syncope (vasovagal syncope)].
AB  - The clinical significance of quantitative tilt-table examination with TCD
      monitoring in the diagnosis of neurocardiogenic syncope is evaluated. A 50-year
      old male suffered a neurocardiogenic syncope during tilt-table examination with a
      strong drop in blood pressure, an increase in cerebrovascular resistance as
      evidenced by transcranial Doppler monitoring, and a 30-s cardiac asystole,
      followed by a generalized seizure. No further syncope could be elicited during
      tilt-table examination after beta-blocker treatment. It was hypothesized that
      hyperactivity of the left ventricular mechanoreceptors due to increased force of
      ventricular contraction during a state of reduced venous backstream to the heart
      was responsible for eliciting the neurocardiogenic syncope. Tilt-table
      examination with an upright position for at least 45 min enables the diagnosis of
      a neurocardiogenic syncope to be made with sufficient sensitivity and
      specificity. Several studies have shown that medication with beta-blockers is
      successful in the treatment of neurocardiogenic syncope. The implantation of
      cardiac pacemakers should only be considered if medication is not successful.

PMID- 7715751
TI  - [Therapy of cerebral aneurysms and arteriovenous vascular malformations in
      hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease)].
AB  - Little is known about the course of cerebral aneurysms in hereditary hemorrhagic
      teleangiectasia (Rendu-Osler-Weber's disease). Thus, therapeutic decisions are
      often difficult. For the first time, we report the successful embolization of an
      arteriovenous fistula and multiple aneurysms of the posterior inferior cerebellar
      artery (PICA) of a patient with Rendu-Osler-Weber's disease after subarachnoid
      hemorrhage. Two years later she suffered another severe intracranial hemorrhage.
      Angiography revealed an aneurysm in the same artery (PICA), which spontaneously
      disappeared within 2 months. Spontaneous regression of aneurysms in Rendu-Osler
      Weber's disease has not been reported before.

PMID- 7715752
TI  - [Nuclear magnetic resonance tomography in multiple sclerosis. Comparison of
      spinal and cerebral findings].
AB  - Out of a total number of 49 patients with clinically defined multiple sclerosis
      46 were examined by cerebral and 44 by spinal MRI. Fifteen out of 44 patients
      with a sensory level as a symptom of spinal cord lesion on neurological
      examination had corresponding lesions in the spinal MRI. Morphological lesions
      were revealed by MRI in three patients without spinal symptoms. There were two
      patients without any spinal signs at clinical examination who had no spinal
      lesions in MRI. In this study the sensitivity of detecting multiple lesions by
      MRI was high with 98% in the brain and 82% in the spinal cord. The number of
      cerebral and spinal MRI lesions was compared. It is concluded that there is a
      correlation between the extent of cerebral and spinal lesions in MRI and the
      clinical status described by the Kurtzke disability status scale.

PMID- 7715753
TI  - [Pseudotransitory ischemic attacks as the initial symptom of multiple system
      atrophy].
AB  - A 59-year-old man presented with an 18-month history of episodes of visual
      disturbance and dysphagia in association with gait unsteadiness and leg weakness
      lasting between 45 and 120 min. These episodes were interpreted as
      vertebrobasilar transitory ischemic attacks. However, they had been preceded by
      impotence for 6 months. Autonomic function tests remained normal until the age of
      62 years when the patient developed documented orthostatic hypotension.
      Parkinsonism was precipitated by neuroleptic treatment at the age of 59 years, at
      which time pyramidal signs were evident. The patient was unable to tolerate
      levodopa preparations and subsequently developed the full clinical picture of
      pathologically proven multiple system atrophy, dying at age 65, 7 years after his
      first symptom.

PMID- 7715754
TI  - [High-grade transverse syndrome caused by echinococcus cysts].
AB  - In this report we present the case of a 16-year-old patient, born in Macedonia,
      who complained of abdominal and back pain and developed paraparesis. On admission
      to hospital, he showed a paraplegic syndrome, the level of sensation being T7,
      together with high-grade paraparesis of the lower extremities and spasticity and
      urinary incontinence. The protein content of the CSF was raised to 183 mg/dl. CT
      and MRI of the thoracic spine showed cystic lesions at the level of the 6th and
      7th thoracic vertebrae, in the paravertebral area and in the 7th rib on both
      sides. The antibody titer of Echinococcus in the serum was positive. To treat
      this problem, corporectomy of the 6th to 8th thoracic vertebrae was performed,
      the area being bridged by a corticospongoid pelvic bone graft and with
      instrumental support of the 5th to 9th thoracic vertebrae. Histological
      examination revealed multilocular Echinococcus lesions. Under long-term treatment
      with mebendazole, the neurological deficits decreased in the postoperative phase.

PMID- 7715755
TI  - [Focal epilepsy with seizures from the supplementary sensorimotor area. False
      interpretation as a spinal disease].
AB  - The symptomatology of focal epileptic seizures depends on the brain region
      involved in the epileptic discharge. We report a case in which ictal
      symptomatology was misinterpreted to be a spinal disease, leading to MRT, CT and
      X-ray of the lumbar region, which revealed normal results. The ictal
      symptomatology consisted of a tingling sensation in the lower back, followed by a
      feeling of tonic tension of the proximal left leg. Ictal EEG video recordings
      consistently revealed an EEG seizure pattern over the right parasagittal
      frontocentral region. We concluded that the patient is suffering from a focal
      epilepsy. The seizures most probably arise from the supplementary sensorimotor
      region. Carbamazepine treatment rendered the patient free of seizures.

PMID- 7715756
TI  - [Adult Leigh syndrome. A rare differential diagnosis of central respiratory
      insufficiency].
AB  - Subacute necrotizing encephalomyelopathy (Leigh's syndrome) is a rare
      neurodegenerative disease in the adult. The precise metabolic defect is unknown,
      but abnormalities of a mitochondrial enzyme system related to cytochrome-c
      oxidase or pyruvate dehydrogenase are described. The clinical picture usually
      consists of an altered breathing pattern, oculomotor paralysis, other signs of
      cranial nerve dysfunction, ataxia, myoclonic jerks, nystagmus, generalized
      seizures, optic atrophy and demyelinating peripheral neuropathy. Hypopnea leads
      to CO2-retention with consecutive loss of consciousness demanding mechanical
      ventilation. Respiratory failure is the most frequent cause of death. Here we
      describe two patients with adult onset Leigh's syndrome and we discuss the
      longterm treatment strategies including vitamin B1 and CPAP mask.

PMID- 7715757
TI  - [Pathogenesis and therapy of multiple sclerosis. The role of cytokines].
AB  - Multiple sclerosis (MS) is probably caused by multiple factors, but there is
      evidence that an autoimmunological process is relevant for the pathogenesis.
      Cytokines can operate in different ways in MS and the animal model "experimental
      allergic encephalomyelitis (EAE). "Interferon gamma (IFN-gamma), tumor necrosis
      factor-alpha (TNF-alpha), TNF-beta, interleukin-1 (IL-1) and IL-2 are important
      inflammation mediators within the MS plaque, whereas IFN-alpha, IFN-beta,
      transforming-growth-factor-beta (TGF-beta) and IL-10 exert mainly
      immunosuppressive functions. Application of these anti-inflammatory cytokines and
      the selective block of pro-inflammatory cytokines are promising new therapeutic
      strategies with fewer side effects than the commonly used cytostatic drugs.

PMID- 7715758
TI  - [Prevention of stroke].

PMID- 7715759
TI  - [Disorders of color perception and increase glare sensitivity in phenytoin and
      carbamazepine therapy. Ocular side effects of anticonvulsants].
AB  - Advanced psychophysical tests, performed in 42 epileptic patients, show that the
      antiepileptic drugs phenytoin and carbamazepine can specifically affect the
      retinal function, while Valproic Acid and the epileptic seizures do not. The
      Farnsworth-Munsell 100-Hue and Panel D-15 desature tests revealed an accumulation
      of errors along the tritan/tetartan axis (blue colour vision deficiencies) and a
      high total error score. The same defect was shown by measurement of the spectral
      sensitivity functions. The results obtained for mesopic vision and especially
      glare sensitivity measured by nyktometry were markedly affected in these patients
      compared to a normal population. The enhanced sensitivity to glare is mainly the
      only one symptom complained by the patient. We propose a screening method for
      early detection of phenytoin- and carbamazepine-induced neurotoxicity. The
      literature of ocular side effects of anticonvulsant drugs is carefully reviewed.

PMID- 7715760
TI  - [Multiple sclerosis and pregnancy. Overview and status of the European
      multicenter PRIMS study].
AB  - This work summarizes the design and state of recruitment of the European
      multicentre prospective PRIMS (PRegnancy In Multiple Sclerosis) project on the
      relationship between pregnancy and multiple sclerosis. Relapse rate, long-term
      effects, influence of delivery and breastfeeding as well as immunomodulation
      during pregnancy and puerperium are reviewed. The results suggest an increase in
      relapse rate during the first 3 months of puerperium with an equal or lessened
      risk during the 9 months of pregnancy. Overall, long-term disability seems not to
      be increased. The mode of delivery or breast-feeding has no adverse effects on
      the course of the disease. Immunological phenomena during pregnancy do not
      correlate to the altered course of MS.

PMID- 7715761
TI  - Changes in the ultrastructural indices of axospinous synapses and the reactions
      of long-term posttetanic potentiation in surviving slices of the sensorimotor
      cortex of mice.

PMID- 7715762
TI  - Regeneration of nerves under the influence of balyse-2 and lactovit.

PMID- 7715763
TI  - Target cells of serotoninergic innervation in the locus coeruleus.

PMID- 7715764
TI  - Influence of immobilization stress on the level of secretion of thyroid hormones.

PMID- 7715766
TI  - Participation of cholinergic systems in the bulbar mechanisms of the regulation
      of breathing.
AB  - The reactions of the respiratory muscles of symmetrical intercostals given bi-
      and unilateral applications of acetylcholine and its antagonists (atropine and
      spasmolytin) to various segments of the dorsal surface of the medulla oblongata,
      the entire region of the projection of the respiratory center, primarily its
      medial or primarily its lateral zones, were studied in rats. A relationship of
      the effect to the level of activity of cholinergic structures and the
      localization of the exposure, was identified. The results obtained suggest an
      uneven distribution of the M and N cholinoreactive systems in homotopic
      structures of the medulla oblongata. A conclusion was drawn of the undoubted
      participation of cholinergic mediation in the mechanisms of integration of paired
      divisions of the bulbar respiratory center and the central regulation of
      respiration.

PMID- 7715765
TI  - Role of bulbospinal respiratory neurons in the generation of the breathing
      rhythm.

PMID- 7715767
TI  - Participation of opiate delta-receptors in immunomodulation.
AB  - The activation of the opiate delta-receptors by the highly specific agonist DSLET
      evokes an immunoinhibitory effect in CBA mice which disappears with preliminary
      blockade of S2 serotonin receptors by cyproheptadine. The blockade of delta
      receptors by the antagonist ICI 174,864 leads to stimulation of the immune
      response, which is tested on the basis of the number of rosette-forming cells.
      Neither stimulation nor suppression of immunogenesis are manifested in animals
      with a transsected hypophyseal stalk; this suggests the central action of the
      opioids. The increase in the immune response obtained with the administration of
      ICI 174,864 is associated with the dopaminergic system, since it is prevented by
      haloperidol. It was demonstrated that the thymus participates in the immune
      stimulating influence of ICI 174,864.

PMID- 7715768
TI  - Structural-functional state of opiate receptors in surviving slices of the
      olfactory cerebral cortex of rats during long-term potentiation.

PMID- 7715769
TI  - Features of the parkinsonian syndrome induced experimentally by a deficit of
      nigrostriatal dopamine and stimulation of cholinergic neurons of the caudate
      nuclei.

PMID- 7715770
TI  - Neurochemical mechanisms of the participation of individual neurons in the
      processes of anticipation and evaluation of the results of behavioral activity.
AB  - The neurochemical mechanisms of the participation of cerebral cortical neurons of
      cats were investigated in this study at various stages of the food-procuring
      behavior during their performance of an instrumental motor act and in instances
      of the unexpected appearance of a portion of milk in the food dispenser. The
      technique of the microiontophoretic application of agents to the cortical neurons
      was used in this study. It was demonstrated that the neurons exhibit varied
      chemical sensitivity to different agents in the period of expectation of
      reinforcement and at the moment of the appearance of the portion of milk. The
      dynamics of the impulse activity depended on the level of activity of the protein
      synthesizing apparatus of the neurons.

PMID- 7715771
TI  - Influence of new ACTH fragments on self-stimulation, avoidance, and grooming
      behavior in rabbits.
AB  - The effects of new cyclic analogs of ACTH fragments, EHFRWGKPVG-NH2 and KHFRWG
      NH2, which have specific and nonspecific active centers in their structure, in
      the self-stimulation, avoidance, and grooming behavior of rabbits were
      investigated in this study. The intraventricular administration of EHFRWGKPVG-NH2
      in doses of 0.1-2.5 micrograms increased the frequency of self-stimulation (SS),
      while in doses of 4-5 micrograms, it decreased the frequency of self-stimulation.
      The administration of KHFRWG-NH2 in doses of 0.1-5.o micrograms, induced a
      decrease in the frequency of SS by 25-30% in the first 15 min following the
      injections; this indicator returned to the baseline level thereafter, and
      decreased again. SS was more intense after 24-48 h, 5-8% higher than the baseline
      level, and remained practically unchanged over the course of a two-hour
      experiment. The administration of the EHFRWGKPVG-NH2 fragment in doses of 0.5-2.0
      micrograms increased the latent period of the avoidance reaction, decreased the
      time of the anxiety state, and increased the time of the comfort state. In
      addition to these changes, both ACTH fragments induced intense grooming,
      increased the duration of grooming by 200-400% as compared with the control
      animals which were administered physiological solution.

PMID- 7715772
TI  - Neurobiology of the integrative activity of the brain: some properties of long
      term posttetanic heterosynaptic depression in the motor cortex of the cat.
AB  - It has been demonstrated that long-term posttetanic heterosynaptic depression
      (LTHD), manifested in the form of a prolonged decrease in the probability of
      monosynaptic responses of the cell to stimulation of that afferent pathway which
      was not activated during conditioning tetanization of another input, takes place
      in the neocortex, as it does in the hippocampus. LTHD is characterized by such
      properties as its long-term character, cooperativity, and nonspecificity of
      input. LTHD in the nonconditioned input and long-term posttetanic potentiation or
      long-term posttetanic homosynaptic depression in the conditioned input may
      develop both in parallel or independantly of one another. It is hypothesized on
      the basis of the results obtained that LTHD (as is the case with LTP and LTD) is
      a calcium-dependant phenomenon, and that the achievement of a specific level of
      depolarization of the membrane in the region of the disposition of the inactive
      synapses is required for its occurrence. "Contrasting," i.e., a relative increase
      in the efficiency of transmission in the activating synapse, may be effected
      through LTHD; LTHD may be one of the mechanisms underlying forgetting.

PMID- 7715773
TI  - The role of mesoaccumbens--pallidal circuitry in novelty-induced behavioral
      activation.
AB  - When exposed to an environment for the first time, rats express greater
      behavioral activation than rats which were previously habituated to that
      environment. The circuit containing the ventral tegmental area, nucleus accumbens
      and ventral pallidum is required for the expression of locomotor activity
      elicited by amphetamine-like psychostimulants. It was hypothesized that this
      circuit is necessary for the expression of novelty-induced motor activity.
      Dopamine is a neurotransmitter in the projection from the ventral tegmental area
      to the nucleus accumbens, while GABA is contained in the projections from the
      nucleus accumbens to the ventral pallidum and from the ventral pallidum back to
      the ventral tegmental area. Prior to exposing rats to a novel or habituated
      environment, they received a microinjection of either saline vehicle or one of
      the following drugs: fluphenazine (dopamine antagonist) into the nucleus
      accumbens, muscimol (GABAA agonist) into the ventral pallidum, or baclofen GABAB
      agonist) into the ventral tegmental area. Each of these pretreatments prevented
      novelty-induced motor activation without suppressing the activity of habituated
      animals. In contrast, when these microinjections were made into adjacent motor
      nuclei of the basal ganglia, including fluphenazine into the striatum, muscimol
      into the globus pallidus and baclofen into the substantia nigra, they were
      ineffective in blocking novelty-induced motor activity. These data indicate that
      the integrity of the circuit that contains the ventral tegmental area, nucleus
      accumbens and ventral pallidum is required for the manifestation of novelty
      induced motor activity.

PMID- 7715774
TI  - Fluctuations in nucleus accumbens dopamine during cocaine self-administration
      behavior: an in vivo electrochemical study.
AB  - High-speed chronoamperometry with Nafion-coated monoamine-sensitive carbon fiber
      electrodes was used to estimate changes in extracellular dopamine concentration
      in the nucleus accumbens during cocaine self-administration behavior in rats. In
      trained animals, time-locked biphasic fluctuations in dopamine-dependent
      electrochemical signal were found to accompany cocaine self-injections (0.8-0.9
      mg/kg/inj). The mean signal gradually increased by the equivalent of 20-30 nM of
      dopamine during the 60 s preceding the injection, reached a peak value at the
      lever-press and decreased abruptly by about 20-30 nM for 40-60 s after the
      injection. This cyclic pattern was repeated with the next lever-press. The post
      cocaine signal decreases were most pronounced during the first 30 min of each
      session, when self-administration behavior was highest (eight to 16 injections),
      and gradually diminished during the session. In contrast, the pre-injection
      signal increases became enhanced over time. Lever-presses reinforced by a double
      cocaine dose were followed by significantly larger and longer lasting signal
      decreases. These biphasic fluctuations quickly disappeared after several non
      reinforced lever-presses. Although experimenter-delivered cocaine injections
      paced to mimic the pattern of self-administration also induced biphasic signal
      fluctuations, both the post-drug signal decreases and subsequent pre-injection
      increases were significantly smaller. It is hypothesized that the increases in
      signal seen in trained animals are a consequence of cocaine-induced dopamine
      uptake inhibition following behavior-associated dopamine cell activation. In
      contrast, the post-cocaine abrupt transient signal depression may be related to a
      decrease in mesolimbic dopamine release due to inhibition of dopamine cell
      activity. Signal decreases seen after self-administered procaine suggest that
      cocaine's local anesthetic action may contribute to this decrease in dopamine
      release. Additionally, while the latency of response differed somewhat, since
      apomorphine administration also led to a reduction in signal, autoreceptor
      activation may also have contributed to the cocaine-induced signal depression.
      That learning and behavioral mechanisms are also important determinants of the
      observed cocaine-induced signal changes is suggested by the signal decreases
      after the first non-reinforced responses, signal differences between self- and
      passively-administered cocaine and signal increases caused by cocaine-related
      cues. In light of numerous neuropharmacological studies implicating the
      significance of the mesolimbic dopamine system in the organization and regulation
      of goal-directed behaviors, these data suggest that mesolimbic dopamine system
      activation may mediate motivational and activational components of drug-seeking
      and drug-taking behavior, while the transient, reward-associated inhibition of
      the system may be involved in regulating these behaviors.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7715775
TI  - Increased dopamine and norepinephrine release in medial prefrontal cortex induced
      by acute and chronic stress: effects of diazepam.
AB  - We have examined the effects of diazepam on the stress-induced increase in
      extracellular dopamine and norepinephrine in the medial prefrontal cortex using
      in vivo microdialysis. In naive rats, acute tail pressure (30 min) elicited an
      increase in the concentrations of dopamine and norepinephrine in extracellular
      fluid of medial prefrontal cortex (+54 and +50%, respectively). Diazepam (2.5
      mg/kg, i.p.) decreased the basal concentration of extracellular dopamine and
      norepinephrine. Diazepam also attenuated the stress-evoked increase in the
      absolute concentrations of extracellular dopamine (+17%), but did not alter the
      stress-induced increase in norepinephrine (+41%). However, when the drug-induced
      decrease in basal dopamine and norepinephrine concentration was taken into
      account, the stress-induced net increase in dopamine above the new baseline was
      equivalent to that obtained in vehicle pretreated rats, whereas the net increase
      in norepinephrine was almost twice that obtained in control subjects. In rats
      previously exposed to chronic cold (three to four weeks at 5 degrees C), tail
      pressure again produced an increase in the concentrations of dopamine and
      norepinephrine in the medial prefrontal cortex (+42% and +92%, respectively).
      However, in these chronically stressed rats, diazepam no longer decreased basal
      dopamine or norepinephrine in extracellular fluid, nor did it affect the stress
      induced increase in the concentrations of these catecholamines. These data
      indicate that diazepam has complex effects on the extracellular concentrations of
      dopamine and norepinephrine which vary depending upon whether the rat is
      undisturbed or stressed during the period of drug exposure as well as the rat's
      prior history of exposure to stress. Moreover, these data raise questions
      regarding the role of catecholamines in the mechanism by which diazepam exerts
      its anxiolytic properties.

PMID- 7715776
TI  - Immune reactions following systemic immunization prior or subsequent to
      intrastriatal transplantation of allogeneic mesencephalic tissue in adult rats.
AB  - We have previously found that dissociated mesencephalic tissue, which differs
      from the host at both major histocompatibility complex and non-major
      histocompatibility complex gene loci, can survive stereotaxic transplantation to
      the striatum of adult rats. We have now studied the outcome of intrastriatal
      neural allografts in rats that were systemically immunized by an orthotopic skin
      allograft either prior or subsequent to intracerebral implantation surgery.
      Dissociated mesencephalic tissue from Lewis rat embryos was stereotaxically
      injected into the dopamine-depleted striatum of hemi-parkinsonian Sprague-Dawley
      rats. One group was immunized by an orthotopic allogeneic skin graft of the same
      genetic origin as the neural graft, six weeks before the neural transplantation
      (the pre-immunized group). Another group was post-immunized by an orthotopic skin
      allograft, six weeks after the neural transplantation (the post-immunized group).
      A control group of rats was not challenged by a skin allograft. Marked
      behavioural recovery was observed in six of seven rats in the control group, in
      six of eight rats in the post-immunized group, and in none of the pre-immunized
      rats. Tyrosine hydroxylase-immunopositive cells were found in rats from the two
      behaviourally compensated groups, but not in the pre-immunized group. The immune
      responses were evaluated by OX-18 (monoclonal antibody against major
      histocompatibility complex class I antigen), OX-6 (major histocompatibility
      complex class II antigen), OX-42 (microglia and macrophages), glial fibrillary
      acidic protein (astrocytes), OX-8 (cytotoxic T-lymphocytes) and W3/25 (helper T
      lymphocytes) immunocytochemistry. All the neural allografts in the pre-immunized
      group were rejected, leaving scars only. There were more intense immune responses
      to the allografts in the post-immunized group than the control group, in terms of
      immunocytochemically higher expression of major histocompatibility complex class
      I and II antigens and more intense cellular reactions consisting of macrophages,
      activated microglia and astrocytes, in addition to CD8- and CD4-positive
      lymphocytes. In summary, the results show the following: (i) systemic pre
      immunization leads to complete rejection of intrastriatal neural allografts,
      implying that the status of the host immune system before transplantation
      determines the outcome for intrastriatal neural allografts; (ii) established
      intrastriatal neural allografts can survive for at least six weeks after systemic
      immunization, in spite of increased host immune responses in and around the
      allografts; (iii) there are no marked immune reactions against intrastriatal
      neural allografts 13 weeks after implantation in rats which have not been
      systemically immunized by a skin allograft; (iv) pre-immunized rats may provide a
      very useful animal model to investigate the role of inflammatory lymphokines in
      immune rejection and to test alternative immunosuppressive drugs.

PMID- 7715777
TI  - Integration of hippocampal suspension grafts with host neocortex.
AB  - The possibility of histological and functional integration of nervous tissue
      heterotopically grafted into the adult host brain was investigated. Suspensions
      of embryonic (E17-18) rat hippocampus with dentate fascia were placed into acute
      cavities in the barrel field of young adult rats (n = 25). Golgi-Cox silver
      impregnation and Cresyl Violet stain were used for histological analysis 3-4
      months postgrafting. The surviving grafts were present in 80% of the grafted
      animals. Only three out of 20 surviving grafts were completely isolated from the
      surrounding host brain; other grafts had areas of direct confluence with the host
      neuropil. Extracellular recording of neuronal activity revealed normal
      spontaneous activity typical of the hippocampus in the majority of the grafts.
      Electrical stimulation of the posterior nucleus of the thalamus, homolateral
      motor neocortex, contralateral barrel field, and sensory stimulation of the host
      evoked responses in 50-60% of the grafted neurons. This did not differ
      significantly from the responsiveness of the similarly tested neurons of
      homotopic neocortical suspension grafts. The latencies of the responses in the
      hippocampal grafts were consistently longer (by about 10 ms) than in the
      neocortical ones. Comparison of the hippocampal suspension grafts with other
      types of hippocampal and neocortical grafts suggests that under certain
      conditions heterotopic tissue can be successfully integrated into the host brain.
      Development of the host-graft interconnections depends on topical proximity, the
      presence of denervated synaptic loci in both tissues, elimination of the
      intragraft neuronal targets and disruption of the intrinsic connections between
      them.

PMID- 7715778
TI  - N-methyl-D-aspartate receptors are critical for mediating the effects of
      glutamate on intracellular calcium concentration and immediate early gene
      expression in cultured hippocampal neurons.
AB  - The mechanisms by which activation of excitatory amino acid receptors is coupled
      to the regulation of gene transcription were studied using cultured hippocampal
      neurons from neonatal rats. Voltage recording, calcium imaging, specific RNA
      analysis and immunocytochemistry were carried out on sister cultures. This
      allowed analysis of the expression of functional glutamate receptor subtypes,
      examination of their role in controlling intracellular free calcium ([Ca2+]i),
      and determination of their relative contributions to the transcriptional
      regulation of six immediate early genes c-fos, fosB, c-jun, junB, zif/268 (also
      termed Egr-1; NGFI-A; Krox-24) and nur/77 (also termed NGFI-B). Expression of all
      six immediate early genes was induced in hippocampal neurons by glutamate
      treatment. Nuclear run-on assays demonstrated that this induction occurred at the
      transcriptional level. Activation of the N-methyl-D-aspartate subtype of
      glutamate receptor was necessary and sufficient for the transcriptional response.
      Non-N-methyl-D-aspartate receptors, while present in cultured hippocampal
      neurons, contributed relatively little to the regulation of transcription.
      Calcium imaging showed that glutamate-induced changes in [Ca2+]i were almost
      entirely mediated by N-methyl-D-aspartate receptors, rather than by L-type
      voltage-sensitive calcium channels. Previous studies have shown that stimulation
      with selective agonists of either N-methyl-D-aspartate receptors, non-N-methyl-D
      aspartate receptors, or L-type calcium channels can lead to an increase in
      [Ca2+]i and c-fos expression. Here we demonstrate that in our hippocampal culture
      system glutamate controls [Ca2+]i and induces immediate early gene transcription
      primarily by activating N-methyl-D-aspartate receptors.

PMID- 7715779
TI  - Morphogenetic effect of kainate on adult hippocampal neurons associated with a
      prolonged expression of brain-derived neurotrophic factor.
AB  - Intraperitoneal or intrahippocampal injections of kainate induce both hippocampal
      cell death and axonal remodeling of the dentate gyrus granular neurons. We report
      here that injection of kainate into the dorsal hippocampus of adult mice may also
      trigger a conspicuous and long-lasting global trophic response of granule cells.
      Morphological changes include somatic and dendritic growth and increased nuclear
      volume with ultrastructural features characteristic of neuronal development. The
      trophic response is correlated with a specific overexpression of brain-derived
      neurotrophic factor that is maintained for at least six months. This shows that
      plasticity in adult neurons can, in addition to axonal remodeling, extend to
      generalized cell growth. Our results further suggest that brain-derived
      neurotrophic factor could be involved in the activation and/or maintenance of
      this phenomenon.

PMID- 7715780
TI  - Regional changes in c-fos expression in the basal forebrain and brainstem during
      adaptation to repeated stress: correlations with cardiovascular, hypothermic and
      endocrine responses.
AB  - Acute stress is known to evoke a discrete pattern of c-fos expression in the
      brain. The work reported here shows that this pattern is modified in regionally
      specific ways following repeated stress, and that this can be correlated with
      changes in telemetered heart rate, core temperature and corticosterone output
      that occur during adaptation. Intact male rats were restrained for 60 min daily
      for one or 10 days. Stress-induced tachycardia was maximal 10 min following the
      onset of restraint, and decreased thereafter. The peak value was not altered by
      repeated restraint, but levels fell towards baseline values more rapidly with
      increasing bouts of stress. Core temperature showed marked reduction during the
      first 10 min of the initial stress, followed by a minor (and not very consistent)
      overshoot during the remainder of the stress period. In contrast to heart rate,
      stress-induced hypothermia did not alter during repeated restraint.
      Corticosterone was raised dramatically immediately following the first 60-min
      session of restraint, and this was attenuated by repeated stress. Sixty minutes
      after the end of the first stress session, there was pronounced c-fos expression
      in the lateral septum, lateral preoptic area, lateral hypothalamic area, all
      divisions of the hypothalamic paraventricular nucleus, the medial (but not
      central) amygdala, the locus ceruleus and a brainstem structure (thought to be
      Barrington's nucleus), compared to rats transferred to the testing room but not
      restrained. Sixty minutes after the 10th stress session, c-fos expression was
      markedly decreased in some of these areas compared with the pattern observed
      after the first stress, especially in the paraventricular nucleus (dorsal and
      medial parvicellular regions) and in medial amygdala. However, all other areas
      measured demonstrated a sustained response even after repeated stress. There were
      no significant differences in c-fos expression in rats repeatedly transferred to
      the testing room (but not stressed) compared to singly transferred counterparts.
      These results show that both neuronal and physiological responses adapt to a
      repeated stress, but that in both cases this has highly specific components. It
      seems likely that adaptive changes in c-fos expression are associated with those
      in some features of autonomic and endocrine reactions. It is noteworthy that
      there is evidence that the lateral septum, in which c-fos expression did not
      diminish after repeated stress, may be involved in temperature control, whereas
      the paraventricular nucleus, in which c-fos did alter, has been linked with both
      cardiac and corticoid regulation.

PMID- 7715781
TI  - Alterations in sensitivity to intracerebral vasopressin and the effects of a V1a
      receptor antagonist on cellular, autonomic and endocrine responses to repeated
      stress.
AB  - We have shown previously that repeated restraint stress results in differential
      adaptation at both macrophysiological and cellular levels. Chronic stress
      accentuates vasopressinergic control of adrenocorticotropic hormone secretion in
      the pituitary. The present work determined whether endogenous vasopressin plays a
      role in response to repeated restraint. The first experiment explored changes in
      the response of repeatedly stressed animals to intracerebral vasopressin
      infusions. The second determined the effect of pretreating rats with a
      vasopressin V1a receptor antagonist on the way that they adapted to repeated
      restraint. Experiment 1: rats were subjected either to daily 60-min restraint for
      10 days or transferred to the testing room where restraint sessions took place
      (controls). On the 11th day, they were infused with either artificial
      cerebrospinal fluid or 250 pmol vasopressin. The behavioural response to
      vasopressin was unaltered by previous stress. Plasma corticosterone was lowered
      in vasopressin-treated rats only after previous stress. Sixty minutes after
      vasopressin infusion, the central amygdala, locus coeruleus, the nucleus of the
      solitary tract and the dorsal vagal nucleus expressed increased levels of c-fos,
      and there were significant two-way interactions between stress and infusion for
      dorsal paraventricular nucleus, locus coeruleus and dorsal vagal nucleus. One-way
      analysis suggested that previous stress also reduced the c-fos response to
      vasopressin in the nucleus of the solitary tract. These results show that
      previous stress causes differential alterations in behavioural, endocrine and
      cellular responses to vasopressin. Experiment 2: rats were implanted with a
      transmitter which monitored heart rate and core temperature and a lateral
      cerebroventricular cannula. For 10 days, either artificial cerebrospinal fluid or
      2500 pmol V1a antagonist, [d(CH2)1(5)-O-Me-Tyr2-Arg8]-vasopressin were infused
      i.c.v. 10 min prior to a 60-min restraint session. On the 11th day, no infusions
      were carried out, but rats received the usual period of restraint. The
      vasopressin antagonist was followed by motor responses (freezing, grooming and
      burrowing), more evident during the third and fifth days of stress. Core
      temperature responses were altered by the antagonist: stress-induced hypothermia
      was greatly reduced. Reduced baseline core temperatures, observed in controls as
      successive stress proceeded, were absent in antagonist-treated rats. By contrast,
      there were no significant effects of vasopressin antagonism on stress-induced
      tachycardia, nor in the way that this adapted to repeated restraint. On the 11th
      day (no i.c.v. infusions), hypothermic responses were no different in rats
      previously receiving either antagonist or control vehicle, but secondary
      hyperthermia was greater in the first group. Corticosterone levels were not
      altered by previous i.c.v. infusions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7715782
TI  - Characterization of synaptic connections between cortex and deep nuclei of the
      rat cerebellum in vitro.
AB  - Intracellular recordings were used to characterize the inhibitory synapses formed
      by Purkinje cells on neurons in the deep cerebellar nuclei of the rat. This work
      was performed on organotypic cerebellar cultures where functional connections
      between Purkinje cells and deep cerebellar neurons are formed de novo. After
      blocking ionotropic excitatory amino acid, and GABAA receptors with 6-cyano-7
      nitro-quinoxaline-2,3-dione,D-2-amino-5-phosphonovalerate and bicuculline,
      respectively, the majority of deep cerebellar neurons fired spontaneously without
      accommodation. This tonic firing was linearly dependent on membrane potential and
      was abolished with hyperpolarization. Bath application of muscimol and baclofen
      reversibly hyperpolarized deep cerebellar nuclei cells. In the presence of
      excitatory amino acid receptor antagonists, field stimulation within the Purkinje
      cell layer induced monosynaptic inhibitory potentials in deep cerebellar neurons
      that were graded and completely blocked by bicuculline. Inhibitory potential
      amplitudes were not markedly reduced during fast repetitive stimulation of
      Purkinje cells, and the resulting hyperpolarization was not affected by the
      competitive GABAB receptor antagonist CGP 35348. A single inhibitory potential
      temporarily interrupted trains of action potentials induced in deep cerebellar
      cells by short depolarizing pulses. Trains of five inhibitory postsynaptic
      potentials, evoked at 20 Hz, induced a hyperpolarization which transiently
      blocked the spontaneous firing of deep cerebellar cells. The efficiency to block
      action potential discharges depended on the frequency of evoked inhibitory
      potentials. Bath application of bicuculline induced burst discharges in the
      control solution. When the excitatory amino acid receptors were pharmacologically
      blocked, bicuculline depolarized deep cerebellar neurons inducing sustained
      action potential discharges. In the presence of tetrodotoxin, bicuculline
      abolished miniature inhibitory postsynaptic potentials and resulted in a membrane
      depolarization of deep cerebellar cells. We conclude that deep cerebellar neurons
      isolated from synaptic inputs display a pacemaker-like activity. Although these
      neurons possess GABAA and GABAB receptors, we confirm that only GABAA receptors
      were involved in the generation of inhibitory postsynaptic potentials, even with
      high frequency stimulation. The amplitude of evoked inhibitory potentials was
      weakly frequency-dependent, thus allowing a powerful inhibition of the pacemaker
      like activity by trains of evoked inhibitory postsynaptic potentials.
      Additionally, spontaneous and miniature inhibitory potentials control the
      excitability of deep cerebellar neurons by exerting a continuous hyperpolarizing
      tone.

PMID- 7715783
TI  - Localization of corticotropin-releasing hormone in the human locus coeruleus and
      pedunculopontine tegmental nucleus: an immunocytochemical and in situ
      hybridization study.
AB  - The present study utilized immunocytochemistry and in situ hybridization
      histochemistry to examine the localization of corticotropin-releasing hormone
      immunoreactivity and messenger RNA in neurons of the human brainstem. A large
      population of corticotropin-releasing hormone-immunoreactive neurons appeared in
      the lateral region of the pontomesencephalic tegmentum. These corticotropin
      releasing hormone-containing neurons are predominantly located in the compact
      subnucleus of the pedunculopontine tegmental nucleus. Proceeding caudally,
      corticotropin-releasing hormone-immunoreactive neurons in the pedunculopontine
      tegmental nucleus travel in a dorsomedial direction approaching the ventral
      border of the locus coeruleus in a dispersed fashion and cluster in a region
      ventromedial to the locus coeruleus which corresponds to the ventral aspect of
      the laterodorsal tegmental nucleus. Dense corticotropin-releasing hormone
      immunoreactive fibers are present in the dorsal portion of the locus coeruleus
      and are most prominent in the middle to rostral levels of the nucleus. The
      cellular and regional localization of corticotropin-releasing hormone messenger
      RNA in the human brainstem is identical to the perikaryal distribution visualized
      by immunocytochemistry. Neurons in the laterodorsal tegmental nucleus and
      pedunculopontine tegmental nucleus express abundant levels of corticotropin
      releasing hormone messenger RNA as revealed by dense silver grains overlying
      these neurons on the emulsion autoradiograms. Within the locus coeruleus, the
      cellular expression of corticotropin-releasing hormone-immunoreactive and
      corticotropin-releasing hormone messenger RNA is exclusively localized to non
      pigmented neurons. The present study confirms a previous finding describing dense
      corticotropin-releasing hormone-immunoreactive fibers innervating the human locus
      coeruleus and extends these findings by identifying corticotropin-releasing
      hormone immunoreactive and corticotropin-releasing hormone messenger RNA
      containing perikarya in the pedunculopontine tegmental nucleus, in the ventral
      portion of the laterodorsal tegmental nucleus and in the locus coeruleus proper.
      From morphological observations, the corticotropin-releasing hormone-containing
      neurons in human pontomesencephalic tegmentum form a continuous population of
      neurons that are positioned anatomically to exert a putative neuromodulatory
      influence on locus coeruleus neurons.

PMID- 7715784
TI  - Sensory and sympathetic contributions to nerve injury-induced sensory
      abnormalities in the rat.
AB  - Peripheral neuropathy can be associated with a variety of symptoms, including
      spontaneous unpleasant sensations and pain, as well as increased sensitivity to
      sensory stimuli. A peripheral neuropathy model involving an L5 spinal nerve
      lesion in male rats has been used to gain insight into the mechanisms that
      underlie symptoms that develop after nerve injury. This model was used to study
      the involvement of sensory fibres, the sympathetic postganglionic neuron and the
      role of nerve growth factor in the induction and maintenance of altered sensory
      function in the nerve territory of the intact L4 spinal nerve. Sensory testing
      was done with calibrated von Frey filaments and a radiant heat apparatus
      [Hargreaves K. et al. (1988) Pain 32, 77-88] and the occurrence of abnormal
      spontaneous behaviour was recorded. L5 spinal nerve resection produced increased
      mechanical and heat sensitivity as well as abnormal spontaneous behaviours.
      Surgical sympathectomy at the L5 but not at the L4 spinal nerve level alleviated
      all sensory abnormalities. However, a lesion of preganglionic fibres to the L5
      level had no significant effect on sensory abnormalities. Thus, sympathetic
      postganglionic neurons at the level of spinal nerve injury can contribute to
      neuropathy symptoms independent of input from preganglionic neurons.
      Postganglionic sympathetic nerve crush alone led to increased mechanical
      sensitivity but not to increased heat sensitivity nor to abnormal spontaneous
      behaviour, further emphasizing the role of sympathetic postganglionic neuron
      changes for the development of increased mechanical sensitivity. An L5 spinal
      nerve resection in rats treated neonatally with capsaicin induced increased
      mechanical sensitivity which was slower in onset and lower in magnitude than that
      in untreated littermates and was abolished by postganglionic sympathectomy. Nerve
      growth factor perfused onto the cut L5 spinal nerve also markedly delayed the
      onset of increased mechanical sensitivity. Two pathophysiological mechanisms
      leading to central changes may be necessary to produce altered sensations in this
      model: (i) ongoing activity in C-fibres, independent of sympathetic
      postganglionic neuron activity and (ii) activity in sensory fibres modulated by a
      sensory-sympathetic interaction in the injured spinal nerve or dorsal root
      ganglion. The sympathetic postganglionic neuron contribution is independent of
      preganglionic sympathetic outflow from the central nervous system, suggesting a
      novel mechanism by which sympathetic efferent terminals can regulate sensory
      fibre activity. A contribution of a loss of neurotrophic factors to the
      sympathetic postganglionic neuron following nerve lesion is also suggested to
      contribute to the symptoms induced by the spinal nerve lesion.

PMID- 7715785
TI  - Multiple second messenger systems act sequentially to mediate rolipram-induced
      prolongation of prostaglandin E2-induced mechanical hyperalgesia in the rat.
AB  - In this study we have evaluated the mechanisms mediating the prolonged
      hyperalgesia induced by administration of prostaglandin E2 plus rolipram, an
      inhibitor of type IV phosphodiesterase. The Randall-Selitto paw pressure device
      was employed to measure the effect of intradermal injection of test agents on the
      time course of the decrease in mechanical nociceptive threshold produced by
      prostaglandin E2 plus rolipram in the hairy skin of the hindpaw of the rat. The
      intradermal injection of prostaglandin E2 produced a dose-dependent decrease in
      the nociceptive threshold which lasted approximately 2 h. While rolipram alone
      had no significant effect on nociceptive threshold, it enhanced and prolonged (>
      72 h) prostaglandin E2-induced hyperalgesia. WIPTIDE, a protein kinase A
      inhibitor, when administered 30 min after prostaglandin E2, or with prostaglandin
      E2 plus rolipram, a time when prostaglandin E2-induced hyperalgesia was at its
      peak, produced a significant reduction in hyperalgesia. However, at 90 or at 180
      min after injection of prostaglandin E2 plus rolipram, WIPTIDE was found to be
      without effect. H-8, a protein kinase G inhibitor, and okadaic acid, a protein
      phosphatase inhibitor, when administered 30 min after prostaglandin E2, or 180
      min after prostaglandin E2 plus rolipram, produced no significant effect.
      However, when administered 90 min after prostaglandin E2 plus rolipram, each
      produced a significant reduction in the hyperalgesia induced by prostaglandin E2
      plus rolipram.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715786
TI  - Ultrastructure of calcitonin gene-related peptide-immunoreactive, unmyelinated
      afferents to the cat carotid body: a case of volume transmission.
AB  - To relate the ultrastructure of unmyelinated afferents to the cat carotid body
      with the known electrophysiological properties of cat chemosensory C-fibers, we
      took advantage of the fact that the calcitonin gene-related peptide is
      exclusively present in a population of sparsely branched afferents to the carotid
      body. They have a morphology identical to the afferents originating from carotid
      sinus nerve unmyelinated axons. Immunoreactive axons were stained using pre
      embedding protocols and horseradish peroxidase-labeled secondary antibody.
      Labeling was present only in unmyelinated axons and boutons distributed in the
      interstitial and parenchymal tissue. The varicosities had an average diameter of
      0.7 micron, and contained both small, clear vesicles and larger dense-core
      vesicles. No labeled axons were ever seen to contact glomus cells, but could be
      observed as close as 0.2 micron to a glomus cell, always with an interposed glial
      process. With a very sensitive protocol, that used tungstate-stabilized
      tetramethylbenzidine as the chromogen, amorphous deposits of reaction product
      were often detected in the extracellular space around a labeled bouton. We
      interpret these findings as indicating that the reciprocal chemical transmission
      between the oxygen-sensitive glomus cells and the unmyelinated afferents takes
      place through non-synaptic transmission, via the rather large extracellular space
      of the carotid body. In addition, the larger distances between glomus cells and
      unmyelinated afferents could explain the lowered sensitivity and sluggishness of
      chemosensory C-fibers, compared to the A-fibers.

PMID- 7715787
TI  - Multiple second messenger routes enhance two high-voltage-activated calcium
      currents in molluscan neuroendocrine cells.
AB  - Two types of high-voltage-activated calcium currents were identified in whole
      cell voltage-clamp recordings of the neuroendocrine caudodorsal cells, which
      control egg-laying in the freshwater snail Lymnaea stagnalis. The currents were:
      (i) a rapidly inactivating high-voltage-activated current, with an activation
      threshold of -40 mV and maximal amplitude at +10 mV; and (ii) a slowly
      inactivating high-voltage-activated current, with a threshold of -10 mV and a
      peak at +30 mV. Both currents were reduced by nifedipine and verapamil, but not
      by omega-conotoxin GVIA, suggesting that they belong to the L-type family of
      calcium currents. The voltage-dependence of inactivation of the rapidly
      inactivating high-voltage-activated current was bell-shaped. Time-constants of
      inactivation ranged from 10 to 25 ms. Steady-state inactivation was characterized
      by a potential of half maximal inactivation of -21.7 +/- 3.4 mV and a slope
      factor of 8.1 +/- 1.7 mV. The voltage-dependence of inactivation of the slowly
      inactivating high-voltage-activated current was S-shaped. Time-constants of
      inactivation increased with depolarization up to a maximum of 300 ms. The steady
      state inactivation parameters were a potential of half maximal inactivation of
      +6.8 +/- 2.2 mV and a slope factor of 6.0 +/- 1.1 mV. The membrane-permeable
      analog of cAMP, 8-chlorophenylthio-cyclic AMP, predominantly increased the slowly
      inactivating high-voltage-activated current, and shifted its voltage-dependence
      of activation and inactivation 10 mV to the left. The rapidly inactivating high
      voltage-activated current was slightly increased by 8-chlorophenylthio-cyclic
      AMP. 8-Bromo-cyclic GMP and the phorbol ester, 12-O-tetradecanoyl-13-phorbol
      acetate, had qualitatively similar effects. Both agents enhanced the rapidly
      inactivating current and, to a lesser degree, the slowly inactivating current,
      without affecting their voltage-dependence. The cyclic AMP-dependent protein
      kinase inhibitor, Walsh inhibitor peptide, antagonized the stimulating effect of
      8-chlorophenylthio-cyclic AMP. The broad-spectrum protein kinase inhibitor 1-(5
      isoquino-linylsulfonyl)-2-methyl-piperazine (H-7) strongly attenuated the effects
      of 8-chlorophenylthio-cyclic AMP, 8-bromo-cyclic GMP and 12-O-tetradecanoyl-13
      phorbol acetate, suggesting that all treatments increase both types of high
      voltage-activated calcium currents through phosphorylation of the channel
      complex.

PMID- 7715788
TI  - Afferent connections of the caudolateral orbitofrontal cortex taste area of the
      primate.
AB  - A cortical taste region has recently been identified in the caudolateral
      orbitofrontal cortex of the macaque. The afferents to this region were
      investigated by means of retrograde tracing, using six injections of wheatgerm
      conjugated horseradish peroxidase. The area of taste cortex was first identified
      physiologically in all the monkeys used in this anatomical study. The four
      injections into the middle and posterior part of this region resulted in large
      numbers of labelled cell bodies in the insular-opercular primary taste cortex.
      Following the two more anterior injections, label was found predominantly in the
      caudal part of the cardolateral orbitofrontal cortex itself. None of the
      injections resulted in labelled cells in the gustatory thalamic nucleus ventralis
      posterior medialis, pars parvocellularis, although all injections resulted in
      label of the mediodorsal nucleus of the thalamus. Afferents were also seen from
      more anterior parts of the orbitofrontal taste cortex, which may represent
      backprojections from subsequent taste areas. These results suggest that the
      caudolateral orbitofrontal cortex contains a higher-order taste cortex.

PMID- 7715790
TI  - Dephosphin/dynamin is a neuronal phosphoprotein concentrated in nerve terminals:
      evidence from rat cerebellum.
AB  - Dephosphin/dynamin is a 94,000/96,000 mol. wt protein kinase C substrate from rat
      brain that is phosphorylated in nerve terminals and dephosphorylated upon
      stimulation of exocytosis and synaptic vesicle recycling. Phosphorylation
      activates an intrinsic GTPase activity and dephosphin may play a role in
      endocytosis [Robinson P. J. et al. (1993) Nature 365, 163-166]. In this study a
      specific polyclonal antiserum to dephosphin was used to investigate its
      distribution in rat brain by immunoblotting and immunocytochemistry. Immunoblots
      of various organs of the rat showed that dephosphin was detectable only in the
      whole brain and not in the testes, lung, kidney, adrenals, heart, liver or
      skeletal muscle. Immunoblotting of various regions of the brain revealed high
      levels of dephosphin, particularly in the hippocampus, cerebellum and cerebral
      cortex, but its absence from the anterior pituitary. Synaptosomes were prepared
      from these three regions and labelled with 32Pi for 60 min, followed by
      incubation in control or 41 mM K+ depolarizing buffer. Dephosphin was present in
      each region and was stoichiometrically dephosphorylated by depolarization,
      indicating the presence and regulation of dephosphin in intact cerebellar nerve
      terminals. The cerebellum was selected for detailed study, using conventional
      light and confocal microscopy, owing to its ordered and well-characterized
      structure. Immunostaining was abundant within the cerebellar cortex and deep
      cerebellar nuclei, but almost entirely absent from the medulla. In the cortex
      many neuronal cells contained dephosphin-like immunoreactivity which was also
      evident in perikarya, axons, and nerve terminals. Dephosphin-like
      immunoreactivity was not detected in the radial Bergman glial cells. The greatest
      concentrations were observed in synaptic terminals, particularly in granular
      layer glomeruli and basket cell terminals surrounding Purkinje cell bodies and
      dendrites. Dephosphin therefore appears to be exclusive to neuronal tissue, but
      is distributed widely throughout the brain. It is located in many neuronal cell
      types of the cerebellum and may be particularly enriched in synaptic terminals,
      where it is regulated by phosphorylation and dephosphorylation. This distribution
      suggests a role for dephosphin in synaptic vesicle cycling in nerve terminals.

PMID- 7715789
TI  - Presynaptic inhibition by baclofen of retinohypothalamic excitatory synaptic
      transmission in rat suprachiasmatic nucleus.
AB  - Optic nerve stimulation evoked monosynaptic excitatory postsynaptic currents in
      suprachiasmatic nucleus neurons maintained in vitro. These currents were
      completely blocked by a combination of glutamate receptor antagonists, 6-cyano-7
      nitroquinoxaline-2,3-dione and 4-aminophosphonovaleric acid. Stimulation of the
      ipsilateral or contralateral suprachiasmatic nucleus produced a biphasic response
      consisting of an excitatory postsynaptic current followed by an bicuculline
      sensitive inhibitory postsynaptic current. Most suprachiasmatic nucleus neurons
      had spontaneous inhibitory and excitatory synaptic currents produced by action
      potential-independent and, less frequently, action potential-dependent release of
      GABA and glutamate. Baclofen reversibly reduced the amplitude of excitatory
      postsynaptic currents evoked by optic nerve stimulation and the effect was
      antagonized by 2-hydroxysaclofen. In addition, baclofen reduced the frequency but
      not the amplitude of the spontaneous miniature excitatory postsynaptic currents.
      In a subset of suprachiasmatic nucleus neurons, baclofen induced an outward
      current, probably by increasing a potassium conductance. Baclofen had no effect
      on either evoked or spontaneous inhibitory postsynaptic currents or on currents
      activated by pulse application of glutamate. These data indicate that activation
      of GABAB receptors can inhibit suprachiasmatic nucleus neurons by two mechanisms.
      The first is to inhibit the release of glutamate from terminals of the
      retinohypothalamic tract. The second is the postsynaptic activation of a
      potassium conductance in a portion of these neurons.

PMID- 7715791
TI  - Changes in arterial blood pressure alter activity of electrophysiologically
      identified single units of the bed nucleus of the stria terminalis.
AB  - The bed nucleus of the stria terminalis may play a role in cardiovascular
      function by way of its connectivity to the diagonal band of Broca/ventral septal
      area. The present study sought to determine whether changes in systemic blood
      pressure affect the electrical activity of single units within the bed nucleus of
      the stria terminalis. Extracellular voltage recordings from neurons in the bed
      nucleus were performed in urethane-anaesthetized rats catheterized for arterial
      blood pressure measurements and for the intravenous administration of pressor and
      depressor drugs. Afferent or efferent connectivity of each recorded neuron was
      determined following electrical stimulation of nearby nuclei with and without
      known barosensitive regions. Of neurons demonstrating efferent connectivity
      (antidromically evoked potentials) with the diagonal band of Broca/ventral septal
      area or habenular nuclei, 24 and 20%, respectively, responded to changes in blood
      pressure with either increases or decreases in firing frequency. Paraventricular
      nucleus-projecting neurons were not affected by alterations in arterial blood
      pressure. Orthodromic potentials (inhibitory and/or excitatory) in the bed
      nucleus were also observed following stimulation of these nearby nuclei. Of these
      orthodromically activated neurons, changes in arterial pressure affected 31% of
      neurons receiving input from the diagonal band of Broca/ventral septal area, 33%
      of neurons with connectivity to the habenular nuclei and 60% of neurons with
      connectivity to the paraventricular nucleus. These data show that the bed nucleus
      of the stria terminalis contains a sub-population of cells that are sensitive to
      deviations in resting arterial pressure and that these cells receive synaptic
      modulation from several limbic/forebrain sources. Furthermore, the results are
      consistent with a role for the bed nucleus in the control of cardiovascular
      function and as a relay nucleus for modified baroreceptor input toward the
      diagonal band of Broca/ventral septal area.

PMID- 7715792
TI  - Pergolide in the treatment of Parkinson's disease.
AB  - Three trials evaluated the efficacy and safety of pergolide. Eighty-six de novo
      patients and 314 patients already receiving levodopa were enrolled in an open
      label study. Of the de novo patients, 47.5% showed a marked or moderate
      improvement and 32% showed a mild improvement. In the levodopa add-on group,
      53.8% showed marked or moderate improvement and 36.3% showed mild improvement. In
      a short-term, double-blind study, the efficacy of pergolide was compared with
      that of bromocriptine. One hundred seventy-two patients were randomized to
      receive pergolide, and 173 were randomized to receive bromocriptine. In de novo
      patients, bromocriptine (n = 49) and pergolide (n = 49) demonstrated similar
      efficacy. However, significantly more levodopa-treated patients in the pergolide
      group, compared with the bromocriptine group, demonstrated marked or moderate
      improvements in several items of the rating scale score. In a long-term study,
      151 of 314 patients receiving pergolide in combination with levodopa remained in
      the study for 3 years, and 127 for 4 years, and in these patients the initial
      improvement was maintained. In 18 of 62 de novo patients, the initial improvement
      was maintained for up to 3 years. These trials indicate that pergolide has
      efficacy in patients with Parkinson's disease, either as monotherapy or in
      combination with levodopa.

PMID- 7715793
TI  - A crossover, controlled study comparing pergolide with bromocriptine as an
      adjunct to levodopa for the treatment of Parkinson's disease.
AB  - A single-blind, crossover study was carried out to compare the efficacy and
      safety of pergolide against that of bromocriptine in 57 patients with Parkinson's
      disease who showed a declining response to levodopa therapy. Patients were
      randomly assigned to receive either bromocriptine followed by pergolide, or
      pergolide followed by bromocriptine. Both drugs were administered for 12 weeks.
      Patients were assessed by a clinician blinded to treatment assignment using the
      New York University Parkinson's Disease Scale. The average daily dose of
      pergolide was 2.3 +/- 0.8 mg and of bromocriptine 24.2 +/- 8.4 mg. Addition of
      pergolide or bromocriptine resulted in a significant improvement in total scores
      when compared with the previous treatment of levodopa alone (pergolide, p =
      0.0001; bromocriptine, p = 0.0005). Pergolide was more effective than
      bromocriptine in daily living scores (p = 0.02) and motor scores (p = 0.038). No
      differences in the incidence of dyskinesias, dystonias, or psychosis were
      observed between groups. Fewer adverse events were recorded in the pergolide
      group, and most patients and physicians preferred pergolide to bromocriptine.
      Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine
      in this short-term trial.

PMID- 7715794
TI  - Dopamine agonists in Parkinson's disease.
AB  - The main pathologic hallmark of Parkinson's disease is a degeneration of the
      dopaminergic cells in the substantia nigra, pars compacta and--to a lesser extent
      -in the ventral tegmental area. Striatal dopamine concentrations are
      significantly reduced before clinical symptoms become apparent. Recent
      neuroanatomic and function studies have revealed that the nigrostriatal
      dopaminergic projection is only one of the neuronal elements integrated into
      extensive basal ganglia-thalamocortical circuits that are intimately involved in
      the regulation of motor activity. The possibilities for therapeutic intervention
      at the level of the different dopamine receptor subtypes and their effect on the
      regulation of motor behavior will be briefly reviewed. Dopamine precursors are
      considered to provide the best symptomatic treatment, whereas dopamine agonists,
      although less effective, might be important in slowing the progression of the
      disease. Our results with pergolide as monotherapy and in combination therapy in
      patients with Parkinson's disease also are discussed.

PMID- 7715795
TI  - The rationale for the use of dopamine agonists in Parkinson's disease.
AB  - Experimental and clinical studies indicate that both dopamine D2-like and D1-like
      receptors are important in reversing the motor symptoms of Parkinson's disease,
      and therefore stimulation of both D1 and D2 receptors may be advantageous in its
      treatment. At present, the role of other receptor subtypes, such as the D3
      receptor, remains unknown, although in primates the D3 receptor might be of
      importance because it exists in significant amounts within the caudate-putamen.
      Both D1 and D2 agonists induce dyskinesias in drug-naive, MPTP-treated primates
      and provoke dyskinesias in levodopa-primed animals. D1 agonists in low doses,
      however, might have antiparkinsonian effects without inducing dyskinesias, and on
      repeated administration perhaps can diminish the intensity of dyskinesias in
      levodopa-primed, MPTP-treated primates. The production of dyskinesias in
      Parkinson's disease might reflect an imbalance in the D1-direct and D2-indirect
      GABAergic output pathways from the caudate-putamen, which colocalize tachykinins
      and enkephalins, respectively. Destruction of the nigrostriatal pathway decreases
      the mRNA for substance P but elevates the mRNA for enkephalin. Treatment with
      levodopa reverses the decrease in substance P mRNA but has either a partial or no
      effect on mRNA for enkephalin. This suggests that levodopa treatment leads to a
      new imbalance between output from the striatum through the direct and indirect
      pathways. In contrast, dopamine agonists appear less able than levodopa to
      manipulate basal ganglia outflow. This might reflect their decreased ability to
      reverse parkinsonian motor deficits or the greater ability of levodopa to provoke
      dyskinesias. Dopamine agonist drugs also might exert neuroprotective
      actions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715796
TI  - Tryptophan hydroxylase can be present in mast cells and nerve fibers of the rat
      dura mater but only mast cells contain serotonin.
AB  - Tryptophan hydroxylase-immunopositive (TPH-I) but not serotonin-I nerve fibers
      were observed in the rat dura mater. This tissue also contained numerous
      serotonin and TPH-I mast cells. The TPH appeared to be located in granules and/or
      enclosed in a juxta-nuclear organite. Westernblots showed that the TPH located in
      the dura mater is similar to the TPH of pineal gland but different from raphe
      TPH. According to the animal, both nerve fiber and mast cell TPH immunoreactivity
      was highly variable in intensity and in number of labelled elements. This
      variability might be due to the complex regulatory mechanisms of TPH as indicated
      by the presence of two types of mast cells.

PMID- 7715797
TI  - Increased concentration of calcitonin gene-related peptide in cerebrospinal fluid
      of depressed patients. A possible trait marker of major depressive disorder.
AB  - Cerebrospinal fluid (CSF) was collected under controlled conditions from subjects
      suffering from major depression (n = 63) or schizophrenia (n = 28) and from
      healthy controls (n = 20). Following Sep-pak extraction, calcitonin gene-related
      peptide immunoreactivity (CGRP-LI) was determined by radioimmunoassay in sample
      aliquots. CGRP-LI concentrations in CSF were increased in the depressed patients
      compared to the schizophrenic and control subjects (P < 0.001). No CGRP-LI
      differences were found between the latter two groups. CGRP-LI did not correlate
      to any of the technical (e.g. storage conditions) or patient (demographic,
      biochemical, or clinical) variables investigated. In view of the CGRP's discrete
      distribution and specific effects in brain and the above results, we hypothesize
      that increased CSF CGRP-LI might be a trait marker of major depression.
      Regardless of the mechanisms (altered synthesis/release/metabolism in brain or
      changed fate in CSF) leading to elevated CSF CGRP-LI, the identification of a
      possible disease trait marker should contribute to the early diagnosis of major
      depression and identification of family members at risk and may help in
      differential diagnosis in other disorders with affective symptomatology.

PMID- 7715798
TI  - Adrenergic innervation of dopamine neurons in the hypothalamic arcuate nucleus of
      the rat.
AB  - Tuberoinfundibular dopaminergic (TIDA) neurons, which represent the final common
      pathway in the inhibitory neuronal control of prolactin (PRL) secretion, are
      regulated by synaptic input from various transmitter systems. Because adrenergic
      receptors at hypothalamic sites were implicated in the central regulation of
      lactotrophs, we hypothesized that a synaptic communication might exist between
      adrenergic pathways ascending from the brain stem and the TIDA system. Polyclonal
      antisera directed towards phenylethanolamine N-methyltransferase (PNMT) and
      tyrosine hydroxylase (TH), biosynthetic enzymes of catecholamines, were used for
      the simultaneous immunocytochemical detection of adrenergic fibers and TIDA
      neurons, respectively, in Vibratome sections of the rat hypothalamus. By the
      light microscopic evaluation of double-immunostained sections, PNMT
      immunoreactive (IR) axon varicosities were localized in juxtaposition to TH-IR
      cell bodies and dendrites in the arcuate nucleus (AN) which contains perikarya
      and dendrites of TIDA neurons. The ultrastructural analysis of contacts provided
      firm evidence for the occurrence of synaptic interactions between the adrenergic
      and TIDA neuronal systems. These morphological findings show that adrenergic
      neurons are involved in the afferent regulation of the TIDA system and indicate a
      putative pathway of central adrenergic effects upon PRL secretion.

PMID- 7715799
TI  - Magnetic field effects on stress-induced analgesia in mice: modulation by light.
AB  - Exposure of adult male CD-1 mice to restraint stress for 60 min increased their
      hindpaw-licking latency in a hot-plate test (50 degrees C); this analgesia was
      significantly reduced after exposure to a stable magnetic field (MF) (30-40 G)
      under white light. In contrast, MF exposure under either red light or total
      darkness did not alter stress-induced analgesia. Results suggest that in rodents
      perception of magnetism might involve a light-dependent mechanism as recently
      found for migratory birds and amphibians.

PMID- 7715800
TI  - Immunohistochemical evidence for amyloid beta in rat soleus muscle in chloroquine
      induced myopathy.
AB  - Deposition of amyloid beta (A beta) is one of the pathological hallmarks of
      brains affected with Alzheimer's disease (AD). The accumulation of A beta have
      been observed in human myopathies with rimmed vacuoles (RVs) which might involve
      lysosomal function. Chloroquine, a potent lysosomotropic agent, induces muscle
      pathology in experimental animals similar to myopathy with RV. In this study, we
      demonstrate, for the first time, immunohistochemical evidence that A beta and
      cathepsin D, a lysosomal enzyme, accumulate in vacuolated rat soleus muscle due
      to chloroquine-induced myopathy. These data indicate that lysosomes are important
      in the metabolism of amyloid precursor protein to generate A beta. This
      experimental system seems to be useful not only to study basic mechanisms
      underlying RV myopathy but also to understand processing of amyloid precursor
      protein to A beta in AD.

PMID- 7715801
TI  - Effects of naloxone, morphine and kappa-opioid receptor agonists on
      hypoxia/hypoglycemia-induced reduction of 2-deoxyglucose uptake in hippocampal
      slices from U-50,488H-tolerant rats.
AB  - The aim of the present study was to determine whether U-50,488H and U-62,066E,
      kappa-opioid receptor agonists cause a neuroprotective action against
      hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose (2-DG) uptake of
      hippocampal slices from U-50,488H-tolerant rats. Both U-50,488H and U-62,066E
      exhibited an attenuating effect on hypoxia/hypoglycemia-induced reduction in 2-DG
      uptake of hippocampal slices. Hypoxia/hypoglycemia-induced deficit of 2-DG uptake
      was prevented by cotreatment with naloxone, an opioid receptor antagonist, but
      potentiated by cotreatment with morphine, a mu-opioid receptor agonist. Chronic
      administration of U-50,488H resulted in the development of tolerance to the
      analgesic effect as well as the neuroprotective effect whereas this treatment
      affected neither basal- nor hypoxia/hypoglycemia-induced decreases in 2-DG
      uptake. Chronic administration of U-50,488H did not modify naloxone-induced
      attenuation of 2-DG uptake deficit but slightly potentiated the morphine-induced
      exacerbation. These findings suggest that the tolerance to kappa-opioid receptors
      does not affect the mu-opioid receptor-mediated neuroprotective or neurotoxic
      action.

PMID- 7715802
TI  - Capsaicin-induced central facilitation of a sympathetic vasoconstrictor response
      to painful stimulation in humans.
AB  - The effect of capsaicin, a compound selectively activating nociceptive primary
      afferent fibers, on a centrally mediated autonomic (sympathetic) vasoconstriction
      response to painful peripheral stimulation was studied in healthy human
      volunteers. Capsaicin (1%) was applied topically to the dorsal forearm and the
      threshold for eliciting a vasoconstriction response in the contralateral
      forefinger to painful electrical or thermal stimulation of the forearm skin
      adjacent to or remote from the capsaicin-treated region was determined with Laser
      Doppler flowmetry. Capsaicin produced a significant decrease of the threshold for
      the vasoconstriction response to painful electrical stimulation of the area of
      central allodynia; i.e., the skin area located adjacent to the capsaicin-treated
      region in which a light touch evoked an unpleasant sensation. Capsaicin did not
      change the threshold for the vasoconstriction response to painful heat stimuli
      applied to the area of central allodynia or to painful electric stimulation
      applied outside the borders of the allodynic area. Heart rate, blood pressure and
      heart vagal tone were not modified by capsaicin. It is concluded that a selective
      activation of nociceptive primary afferent fibers of the skin by capsaicin
      produces a central submodality-dependent facilitation of an autonomic
      vasoconstriction response to noxious stimulation in humans. This central
      facilitation can be explained by segmental excitability changes of afferent
      interneurons at the spinal cord level.

PMID- 7715803
TI  - Regulation of tyrosine hydroxylase gene expression in mesencephalic dopamine
      neurons: effect of imipramine treatment.
AB  - The effects of a chronic imipramine treatment on the mesoamygdaloid pathway of
      rats were examined. Using semiquantitative immunocytochemical techniques, it was
      observed that the level of TH mRNA was decreased in the ventral tegmental area
      (VTA). In contrast, the TH protein was increased in both the VTA and amygdala.
      The TH activity was decreased in the amygdala when assessed under normal
      conditions but increased after a preincubation to phosphorylate the enzyme,
      suggesting a lowering of the protein-specific activity in the terminals. These
      results show that TH protein turnover in the mesoamygdaloid neurons can be
      reduced by chronic imipramine treatments, thereby producing an accumulation of
      inactive TH protein in the neurons while also decreasing TH gene activity in the
      cell bodies.

PMID- 7715804
TI  - Involvement of the glutamate receptor delta 2 subunit in the long-term depression
      of glutamate responsiveness in cultured rat Purkinje cells.
AB  - An antisense oligonucleotide against the glutamate receptor delta 2 subunit mRNA,
      which is selectively expressed only in Purkinje neurons, suppressed the induction
      of long-term depression (LTD) of glutamate responsiveness in the rat cerebellar
      culture. LTD of glutamate response is induced by pairing glutamate application
      and depolarization of a Purkinje cell. Treatment of the culture with the
      antisense oligonucleotide exerted no appreciable effect on basic physiological
      and morphological properties of Purkinje cells, except for LTD induction and
      reduction of delta immunoreactivity which was intense in distal dendrites. Sense
      and missense oligonucleotides, which were used as controls, did not block LTD
      induction. These results suggest that the glutamate receptor delta 2 subunit is
      involved in the cerebellar LTD.

PMID- 7715805
TI  - Major differences between long-term potentiation and ACPD-induced slow onset
      potentiation in hippocampus.
AB  - We examined the effects of a long-lasting application of the selective
      metabotropic glutamate receptor (mGluR) agonist 1S-3R, 1-amino cyclopentane-1,3
      dicarboxylic acid (ACPD) on synaptic potentials recorded from the CA1 and CA3
      subfields in hippocampal slices maintained in a superfusion slice chamber. In 25%
      of the slices, ACPD generated an slow onset potentiation (SOP) of population
      EPSPs (pEPSPs) in CA1. In contrast to long-term potentiation (LTP) induced by a
      tetanic train, SOP was accompanied by an increase in the magnitude of the
      presynaptic fiber volley. Potentiation of the isolated afferent volley suggests
      that the expression of SOP is due to a recruitment of additional presynaptic
      fibers by the test stimulus caused by the persistent block of K+ channels by
      ACPD.

PMID- 7715806
TI  - In situ hybridization histochemistry of vghm1f mRNA in the rat suprachiasmatic
      nucleus: co-localization with vasopressin/neurophysin and VIP/PHI.
AB  - The expression of vgf gene, first isolated as a gene induced by nerve growth
      factor in PC12 cells, was investigated in neurons of the suprachiasmatic nucleus
      (SCN) by in situ hybridization. In the rat forebrain, the vgf mRNA was found most
      densely in the SCN. Neurons which express vgf mRNA were found both in the
      dorsomedial and ventrolateral subdivisions. Double-labeling of vgf in situ
      hybridization and peptide immunocytochemistry demonstrated that vgf mRNA was
      expressed in most vasopressin- and neurophysin-immunoreactive neurons in the
      dorsomedial part and in vasoactive intestinal peptide (VIP)- and peptide
      histidine isoleucine amide (PHI)-immunoreactive neurons in the ventrolateral
      part. These findings suggest that vgf is a highly expressed gene in both
      vasopressin/neurophysin neurons and VIP/PHI neurons which were speculated to be
      involved in the generation and entrainment of circadian rhythm.

PMID- 7715807
TI  - Constitutive expression of heat shock protein 90 (HSP90) in neurons of the rat
      brain.
AB  - Immunoblot analysis, immunocytochemistry and immuno-electron microscopy were
      employed to study the expression of HSP90 protein in the adult rat brain, using a
      specific polyclonal antiserum. Immunoblot analysis demonstrated equal levels of
      HSP90 in microdissected extracts from hippocampus, cortex, striatum and
      cerebellum. Immunocytochemistry and immuno-electron microscopy provided evidence
      that HSP90 is markedly expressed throughout all neuronal subpopulations of the
      CNS but not in non-neuronal cells except ependyma and choroid plexus. At the
      ultrastructural level, HSP90 immunoreactivity was predominantly found in
      perikarya but to a lesser extent also in dendrites and nuclei. The constitutive
      expression of HSP90 in widespread neuronal cell populations suggests a functional
      role in the physiological molecular program of CNS neurons.

PMID- 7715808
TI  - Presence of nuclear androgen receptor-like immunoreactivity in neurokinin B
      containing neurons of the hypothalamic arcuate nucleus of the adult male rat.
AB  - Dual label immunofluorescence was used in the brain of normal, non colchicine
      treated, adult male rats in order to characterize the neurons possessing the
      nuclear androgen receptor in the hypothalamic arcuate nucleus. The affinity
      purified PG21 rabbit serum to the rat androgen receptor (AR) was used in
      conjunction with a polyclonal guinea pig antiserum to peptide 2, a sequence
      within the precursor to neurokinin B (NKB). All NKB-containing neurons were also
      immunoreactive for the AR, and made up a large proportion (about 60%) of the
      arcuate cells with detectable and specific AR immunoreactivity.

PMID- 7715809
TI  - New observation on ubiquitinated neurons in the cerebral cortex of multiple
      system atrophy (MSA).
AB  - To investigate neuronal damage in the cerebral cortex in patients with multiple
      system atrophy (MSA), immunohistochemical stainings were carried out on the
      prefrontal cortex, the hippocampus, the precentral gyrus, the supplementary motor
      cortex and the occipital cortex in 6 cases of MSA and 6 controls, using
      antibodies against ubiquitin, tau protein and neurofilaments (BF10, RT97, 147).
      In MSA cases, a variable number of neuronal ubiquitinated inclusions were
      observed in the granule cell layer of the dentate gyrus (3/6) and the prefrontal
      cortex (3/6). An increased number of ubiquitinated dots-like structures were also
      observed in the parahippocampal gyrus of MSA cases (4/6) in comparison with
      controls. These results showed further evidence of neuronal damage in the
      cerebral cortex in MSA and strongly suggest a relationship between the cerebral
      cortical pathology and occasional manifestation of cognitive deficits in some MSA
      cases.

PMID- 7715810
TI  - Brain-metabolite transverse relaxation times in magnetic resonance spectroscopy
      increase as adenosine triphosphate depletes during secondary energy failure
      following acute hypoxia-ischaemia in the newborn piglet.
AB  - The adenosine triphosphate (ATP)-dependent sodium/potassium pump extrudes
      intracellular sodium in exchange for extracellular potassium. Low ATP causes pump
      dysfunction increasing both intracellular sodium and water thereby enhancing
      metabolite mobility. This should be detectable by proton magnetic resonance
      spectroscopy (MRS) as increased metabolite transverse relaxation times (T2s).
      During secondary cerebral energy failure in the newborn piglet, proton and
      phosphorus MRS showed large increases in the T2s of choline, creatine, N
      acetylaspartate, and lactate that correlated with ATP depletion. These results
      provide insight into factors affecting metabolite T2s and show that T2s may be
      useful for studying cellular oedema.

PMID- 7715811
TI  - Early 72-kDa heat shock protein induction in microglial cells following focal
      ischemia in the rat brain.
AB  - Focal cerebral ischemia in the adult rat produces induction of 72-kDa heat shock
      protein (HSP-72) in neurons, glia and endothelial cells. Double antigen
      immunocytochemistry was carried out to find out whether microglial cells express
      HSP-72 following 1-h middle cerebral artery (MCA) occlusion. A monoclonal
      antibody against the CR3 complement receptor (OX-42) specific for microglia was
      used followed by a monoclonal antibody against HSP-72. Co-localization of these
      antibodies was seen in cells of the ipsilateral corpus callosum and striatum at 3
      h following 1-h MCA occlusion, and in the ipsilateral striatal penumbra, corpus
      callosum and cortex at 8 h. Results demonstrate that stellate microglial cells
      show an early response to 1-h MCA occlusion by expressing inducible HSP-72, thus
      suggesting that microglial cells are sensitive to the ischemic insult.

PMID- 7715812
TI  - Control of 4-aminopyridine-induced synchronous activity by adenosine A1 and mu
      opioid receptor agonists in adult rat hippocampus.
AB  - In the presence of 4-aminopyridine (4AP, 50 microM) two types of spontaneous
      field potentials can be recorded in the CA3 stratum radiatum of adult rat
      hippocampal slices. First, epileptiform interictal discharges (0.85 +/- 0.25 Hz)
      that are blocked by excitatory amino acid ionotropic receptor antagonists.
      Second, negative-going synchronous potentials (0.036 +/- 0.015 Hz) which are
      solely abolished by application of bicuculline methiodide (BMI). Bath application
      of the specific adenosine A1 receptor agonist, N6-(L-2-phenylisopropyl) adenosine
      (L-PIA), reduced the frequency of interictal discharges in a dose-dependent
      manner (IC50 = 8.75 microM; n = 9 slices) and this effect was reversed by the
      specific adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine
      (DPCPX, 100 microM; n = 3 slices). L-PIA did not affect the frequency of
      occurrence of the negative-going field potential during application of excitatory
      amino acid receptor antagonists. This BMI-sensitive event was depressed, however,
      by application of the mu-opioid receptor agonist [D-Ala2-N-Me-Phe4,Gly5(5)
      ol]enkephalin (DAGO, 10 microM; 15.1 +/- 8.7% of rate in control; n = 6 slices),
      an effect that was antagonized by naloxone (20 microM). Our results indicate that
      L-PIA reduces the 4AP-induced epileptiform activity through the activation of
      adenosine A1 receptors. This procedure does not influence the BMI-sensitive field
      potential, which is abolished, however, by DAGO. Thus, our findings support the
      hypothesis that the BMI-sensitive potential is due to the presynaptic release of
      GABA from interneurons.

PMID- 7715814
TI  - Paradoxical differences in animal models of anxiety among the Roman rat lines.
AB  - The Roman high-avoidance (RHA) and low-avoidance (RLA) rat lines have been
      selected upon their divergent active avoidance behaviours. On the basis of open
      field behavioural analyses, it has been suggested that RLA rats display more
      emotionality than RHA rats. Herein, we have analysed the behaviours of male RHA
      and RLA rats in three tests putatively related to anxiety, namely the elevated
      plus-maze, the black/white box, and the social interaction test. In the elevated
      plus-maze, neither the number of total arm entries nor the percent number of open
      arm entries were different between the Roman lines. Alternatively, RLA rats spent
      more time on the open arms, compared to RHA rats. In the black/white box, both
      the latency to enter the black compartment, the number of shuttles, the time
      spent in the white compartment, and the general activity in the white compartment
      were higher in RLA rats, compared to their RHA counterparts. Lastly, socially
      isolated RHA and RLA behaved similarly when exposed to a social interaction test.
      It is suggested that under particular experimental conditions male RLA rats
      display less anxiety than male RHA rats, and that the open-field test may provide
      indices of activity rather than indices of anxiety.

PMID- 7715813
TI  - Triiodothyronine does not affect the average incorporation of L-[35S]methionine
      in rat brain structures.
AB  - The autoradiographic method with L-[35S]methionine was used to examine the effect
      of acute administration of L-triiodothyronine on local rates of brain protein
      synthesis in free-moving adult rats. Triiodothyronine was given intraperitoneally
      at doses of 12.5 or 25 micrograms kg-1. It did not modify the rate of plasma
      methionine incorporation in the 40 brain regions examined, despite a 4- to 8-fold
      increase of plasma free triiodothyronine levels. Biochemical analysis confirmed
      that triiodothyronine (25 micrograms kg-1) had no apparent effect on the overall
      rate of protein synthesis in the brain as a whole. These results suggest that
      changes in the circulating levels of thyroid hormones do not exert a general and
      direct metabolic effect in brain of intact adult rats.

PMID- 7715815
TI  - The amyloid peptide of Alzheimer's disease is not produced by internal initiation
      of translation generating C-terminal amyloidogenic fragments of its precursor.
AB  - The molecular mechanisms of the amyloid peptide (A beta) production from the
      amyloid precursor protein (APP) remain unclear and it has been suggested that
      initiation of translation at methionine 596, which immediately precedes the A
      beta sequence, could generate soluble amyloidogenic fragments. We show that the
      amyloid peptide is actually produced by expression of the C-terminal 100 residues
      of the APP, using methionine 596 as an initiation codon. However, the amyloid
      peptide is no longer detectable when a stop codon is introduced in the APP mRNA,
      before the A beta coding region. These results strongly suggest that A beta is
      produced by degradation of APP and not by local translation of its mRNA.

PMID- 7715816
TI  - Developmental profile of the hypothalamo-pituitary-adrenal axis response to nerve
      growth factor.
AB  - The developmental profile of the hypothalamo-pituitary-adrenal axis (HPAA)
      response to nerve growth factor (NGF) in the rat was determined. NGF induced HPAA
      activity as assayed by increased serum corticosterone levels in pups that were >
      or = 15 days of age. Since the development of an HPAA response to NGF is parallel
      to synaptogenesis in the hippocampus and to the regulation of HPAA function by
      the hippocampus, these findings support the hypothesis that serum NGF activates
      the HPAA by acting within the CNS.

PMID- 7715818
TI  - Intracerebral injection of polymyxin B blocks the acquisition of conditioned
      taste aversion in rats.
AB  - The contribution of protein kinase C (PKC) to the acquisition of conditioned
      taste aversion (CTA) was tested by injection of three PKC inhibitors--polymyxin
      B, H7 and staurosporine--into the parabrachial nucleus (PBN). From the tested
      drugs only polymyxin B (20 mM) prevented CTA acquisition. Application of H7 (10
      mM) and staurosporine (100 and 500 microM) into the PBN did not impair CTA
      learning. The blocking effect of polymyxin B is dose dependent (5 and 10 mM
      concentration did not disrupt CTA formation) and site specific (application of
      polymyxin B into the visual cortex did not elicit CTA blockade). The ability of
      polymyxin B to disrupt CTA learning is not due to irreversible damage of PBN.
      These results suggest that polymyxin B blocks acquisition of CTA in some
      nonspecific way not necessarily involving inhibition of PKC. This conclusion is
      supported by failure of two other more specific PKC inhibitors to affect CTA
      learning.

PMID- 7715819
TI  - Identification of interleukin-6 (IL-6)-expressing neurons in the cerebellum and
      hippocampus of normal adult rats.
AB  - The cellular source of interleukin-6 (IL-6) in brain has not been identified.
      Using a sensitive, non-radioactive in situ hybridization technique, the cellular
      localization of IL-6 mRNA in different areas of the rat brain was analysed.
      Intense staining for IL-6 mRNA was found in Purkinje cells and hippocampal
      neurons. Our data support an essential role of IL-6 for cerebellar and
      hippocampal neuron differentiation and function.

PMID- 7715817
TI  - Increase of hypothalamic cholinergic activity in 2-deoxyglucose hyperglycemia.
AB  - Under inducement of hyperglycemia by intravenous administration of 2-deoxyglucose
      (2-DG), the contents of choline and acetylcholine (ACh) in the ventromedial
      hypothalamic nucleus (VMH), lateral hypothalamus (LH) and paraventricular nucleus
      (PVN) were analyzed after a microdissection of the microwave treated brains.
      After the administration of 2-DG, the content of choline in those hypothalamic
      nuclei increased markedly, and the ACh decreased in both the LH and the PVN. The
      increment of plasma glucose was reduced in the adrenodemedullectomized rats, and
      simultaneously the increment of the choline in the LH further augmented. These
      results suggest the contribution of hypothalamic cholinergic neurons in 2-DG
      induced hyperglycemia.

PMID- 7715820
TI  - Opposite effects of cholinergic agents and benzodiazepine receptor ligands in a
      passive avoidance task in rats.
AB  - Benzodiazepine (Bzd) agonist, diazepam (Dzp) and inverse agonist methyl beta
      carboline-3-carboxylate (beta-CCM); acetylcholinesterase inhibitor, physostigmine
      (Physo) and muscarinic antagonist, scopolamine (Scopo), were investigated for
      their mnesic effect in a passive avoidance (PA) task in rats. Impairments were
      observed after Dzp- and/or Scopo-pretraining treatments. Physo was without effect
      but antagonized the Dzp-induced impairments. beta-CCM enhanced acquisition and
      antagonized the Scopo-induced impairing effect. All these drugs had no effect in
      posttraining administration.

PMID- 7715821
TI  - Attenuation of ammonia toxicity in mice by PK 11195 and pregnenolone sulfate.
AB  - Ammonia and benzodiazepines are thought to be involved in the pathogenesis of
      hepatic encephalopathy. The present study was undertaken to evaluate the effect
      of various benzodiazepine-receptor ligands and neurosteroids on ammonia toxicity
      in mice. Administration of ammonium acetate (8-15 mmole/kg; i.p.) to Swiss
      Webster mice resulted in a dose-dependent increase in mortality. Pretreatment
      with the central benzodiazepine receptor agonist clonazepam or the antagonist
      Ro15-1788 (7 mg/kg each; i.p.) had no significant effect on the lethal response
      to 10 mmole/kg ammonium acetate. However, pretreatment with the putative
      antagonist of the peripheral-type benzodiazepine receptor, PK 11195 (10 mg/kg;
      i.p.), reduced mortality from 50 to 10%. Ro5-4864 (10 mg/kg; i.p.), an agonist of
      the peripheral-type benzodiazepine receptors, had no effect on ammonia toxicity.
      The neurosteroid, pregnenolone sulfate (20 mg/kg; i.p.) reduced mortality from 50
      to 25%. The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK
      801 (2 mg/kg; i.p.), had no effect on the lethal response to ammonium acetate.
      The results from the present study suggest a role for peripheral-type
      benzodiazepine receptors and specific neurosteroids in the alleviation of ammonia
      toxicity in mice.

PMID- 7715822
TI  - Amphetamine and haloperidol modulatory effects on Purkinje cell activity and on
      EEG power spectra in the acute rat model of epilepsy.
AB  - The modulation of cerebellar Purkinje cell activity and EEG from parietal cortex
      was studied in the rat model of epilepsy induced by penicillin under acute
      haloperidol and amphetamine treatment. The discharge pattern of Purkinje cells
      showed tendency towards inhibition and EEG power spectra increased after
      parenteral administration of penicillin (1000000 IU/kg, i.p.). Acute haloperidol
      treatment (1 mg/kg, i.p.), performed after the development of penicillin induced
      epileptic episodes, elicited a prominent excitation of Purkinje cell discharges
      associated with parallel increase in mean EEG power spectra. However, acute DL
      amphetamine treatment induced marked suppression of Purkinje cell discharges as
      well as outstanding decrease of the mean EEG power spectra. These results
      indicate that cerebellar Purkinje cells may be important in the control of
      seizure activity and that noradrenergic influences are relevant.

PMID- 7715823
TI  - Intrathecal interferon-gamma facilitates the spinal nociceptive flexor reflex in
      the rat.
AB  - The effect of intrathecal (i.t.) injection of the cytokine interferon-gamma) (IFN
      gamma) on the spinal nociceptive flexor reflex was examined in decerebrate,
      spinalized, unanesthetized rats. IFN-gamma elicited an initial intense, brief
      facilitation of the flexor reflex followed by a sustained reflex facilitation
      lasting 40 +/- 5 min (range 20-65 min). The initial and prolonged reflex
      facilitations by IFN-gamma were partially and totally blocked, respectively, by
      i.t. pretreatment with nitro-L-arginine-ester, an inhibitor of nitric oxide
      synthase, at doses which did not influence spinal cord blood flow. Spinal
      application of IFN-gamma produced powerful and prolonged facilitation of the
      flexor reflex, possibly reflecting a hyperalgesic action of this cytokine. The
      facilitatory effect of IFN-gamma was mediated, at least in part, by the
      activation of the L-arginine-nitric oxide pathway. Thus, IFN-gamma released in
      the CNS may participate in eliciting pain and hyperalgesia in infectious or
      neuroinflammatory diseases where there is increased production of this cytokine.

PMID- 7715824
TI  - Antidromic vasodilatation in the striated muscle and its sensitivity to
      resiniferatoxin in the rat.
AB  - Antidromic stimulation at the L4-L5 dorsal roots elicited a blood flow increase
      in ipsilateral muscles of lower extremities in rats measured by laser-Doppler
      flowmetry. Stimulation with 0.5 Hz; 20 V; 0.5 ms; 50 impulses was much less
      effective in muscle (18.9 +/- 6.4 area under the curve (%); mean +/- S.E.) than
      in the glabrous skin (80.5 +/- 8.25; P < 0.001). No significant difference was
      seen at 10 Hz (51.6 +/- 10.6 muscle; 60.6 +/- 17.3 skin). In the muscle the
      latency period of the response was long (37.4 +/- 3.1 s; mean +/- S.E.) at 0.5 Hz
      stimulation and was much shorter (8.8 +/- 0.8 s) at the higher frequency of 10
      Hz, unlike in the skin where latency values at both frequencies were similar (9.7
      +/- 0.8 s and 8.9 +/- 0.9 s, respectively). Antidromic vasodilatation in the
      muscle and the skin was abolished by resiniferatoxin (RTX) in an i.v. dose of 1.0
      microgram/kg. These results provide a direct evidence for the existence of
      antidromic vasodilatation in striated muscle and suggest a mediating role for
      capsaicin/RTX sensitive afferents.

PMID- 7715826
TI  - Convergence of afferents from superior sagittal sinus and tooth pulp on cells in
      the upper cervical spinal cord of the cat.
AB  - Units in the dorsolateral area of the upper cervical cord respond to
      craniovascular stimulation. This study examined tooth pulp responses in this area
      in cats. Eleven of 21 units tested in the dorsolateral area had convergent inputs
      from superior sagittal sinus and tooth pulp; while 10 units had sagittal sinus,
      but not tooth pulp, input. Mean response latency to tooth pulp stimulation (25.8
      ms) was significantly longer than to superior sagittal sinus stimulation (9.8
      ms). Half of the units had cutaneous receptive fields; and in five units, action
      potentials could be evoked by electrical stimulation in the posterior complex of
      the thalamus.

PMID- 7715825
TI  - Production of interleukin-3 by murine central nervous system neurons.
AB  - We examined expression and production of interleukin-3 (IL-3) mRNA and IL-3
      protein in mouse primary cultured neurons and glia by the reverse transcription
      and polymerase chain reaction and a bioassay using an IL-3-dependent cell line.
      IL-3 mRNA was demonstrated mainly in hippocampal neurons but not in glia, while a
      small but definite production of bioactive IL-3 was detected in septal and
      hippocampal neuronal cultures. Thus, endogenous IL-3 might be produced by certain
      neurons in situ.

PMID- 7715827
TI  - Brain activation study by use of positron emission tomography in unanesthetized
      monkeys.
AB  - A system for the measurement of brain activity in conscious monkeys by positron
      emission tomography (PET) was established in the present study. The signal/noise
      ratio was maximal around 40 s for data acquisition in the PET scan with 15O
      labeled water. When the monkey was stimulated by vibration and subtraction images
      of the data sets from regional cerebral blood flow (rCBF) changes in paired
      stimulation and control were superimposed on magnetic resonance images obtained
      from the same specimens, a somatotopic map corresponding to the sites stimulated
      was clearly demonstrated. Visual stimulation with a photic stimulator activated
      the corresponding regions of the primary visual cortex. Comparison of the
      activated sites and extents under the conscious state with those under anesthesia
      assured that the study is controllable; there was little unpredictable activation
      due to unlimited subject movement or to psychological effects.

PMID- 7715828
TI  - Adenosine enhances neuronal damage during deprivation of oxygen and glucose in
      guinea pig superior collicular slices.
AB  - The purpose of the present study was to clarify whether adenosine has a
      neuroprotective effect against neuronal damage during deprivation of oxygen and
      glucose in superior collicular slices. After deprivation of oxygen and glucose
      for 7 min, the concentration of ATP in slices incubated with adenosine (100
      microM) for 60 min was significantly higher (6.43 +/- 0.16 nmol/mg protein, mean
      +/- S.E.M.) than that in slices incubated without adenosine (4.77 +/- 0.61). The
      postsynaptic field potential (PSP) recorded in the superficial gray layer of the
      SC slice completely disappeared within 7 min after deprivation of oxygen and
      glucose and it recovered to approximately 80% of the original amplitude in the
      medium without adenosine. But, in the presence of adenosine (100 microM) during
      and after oxygen and glucose removal, the PSP showed only approximately 40%
      recovery. These results indicate that in the superior colliculus adenosine has no
      protective effect on functional derangement caused by anoxia although it may
      facilitate the resynthesis of tissue ATP during recovery.

PMID- 7715829
TI  - Optimizing liposome-mediated gene transfer in primary rat septo-hippocampal cell
      cultures.
AB  - Although liposomes have been widely employed to transfect DNA into a variety of
      cell types, no previous studies have systematically examined conditions producing
      optimal liposomal-mediated transfection of DNA into central nervous system (CNS)
      cells. Thus, we used the beta-galactosidase (beta-gal) reporter gene to examine
      factors influencing the efficiency of liposome-mediated gene transfection in CNS
      cell cultures. Our results indicate that without increasing the amounts of DNA,
      increased liposome concentrations within certain limits enhanced transfection
      efficiency. However, higher liposome levels could produce cell lysis. Without
      increasing liposome concentrations, increased amounts of DNA did not improve
      transfection efficiency. Employing the optimal concentration (1 microgram DNA/3
      microliters liposomes/well), beta-gal gene expression was sustained for at least
      two weeks after transfection in primary septo-hippocampal cultures.

PMID- 7715830
TI  - Sustained expression of functional nerve growth factor in primary septo
      hippocampal cell cultures by liposome-mediated gene transfer.
AB  - We examined liposome-mediated gene transfection of nerve growth factor (NGF) in
      primary central nervous system cultures. RT-PCR analyses detected increased
      expression of NGF mRNA one day after liposome-mediated NGF gene transfection.
      ELISA studies detected large increases in NGF protein in cells and in culture
      medium after NGF gene transfection. Cells continued to secrete NGF into the
      medium for at least 2 weeks. NGF bioassays confirmed that the NGF secreted after
      gene transfection was biologically active.

PMID- 7715831
TI  - Differential expression pattern of jun B and c-jun in the rat brain during the 24
      h cycle.
AB  - Data from a previous report [3] demonstrated that the proto-oncogene c-fos mRNA
      expression undergoes basally a circadian fluctuation in the rat brain. The
      present study was designed to verify by means of Northern blot hybridization the
      eventual occurrence of a spontaneous oscillation in the expression of other two
      proto-oncogenes, jun B and c-jun, during 24 h. Rats were either entrained to a
      light-dark photoperiod or maintained under constant darkness or light. During the
      dark period, as well as the subjective night, the jun B mRNA levels in the
      cerebral cortex and striatum were 4-6 times higher than in the light hours or
      subjective day. No consistent oscillation was found in the c-jun mRNA expression
      during 24 h in any of the examined brain regions. These results suggest the
      possibility of different interactions of the c-fos, jun B and c-jun gene products
      throughout a 24-h period in discrete brain regions.

PMID- 7715832
TI  - Intrathecal gamma-aminobutyric acidB (GABAB) receptor antagonist CGP 35348
      induces hypersensitivity to mechanical stimuli in the rat.
AB  - Intrathecal (i.t.) administration of the gamma-aminobutyric acidB (GABAB)
      receptor antagonist CGP 35348 in the rat resulted in a dose-dependent pain-like
      response (vocalization) to innocuous mechanical stimuli and touch/pressure). The
      effect was maximally evoked by stimulation applied to a dermatome corresponding
      to the spinal levels of the i.t. injections. The paw withdrawal threshold to
      pressure was also moderately decreased after i.t. CGP 35348. In contrast, i.t.
      CGP 35348 had no effect on the hot plate test. It is suggested that the input of
      low threshold afferents innervating mechanoceptors is tonically inhibited by the
      GABA system through B-type receptors, and blockade of this system results in
      mechanical hypersensitivity that is similar to mechanical allodynia (painful
      response to innocuous stimulation) observed in humans.

PMID- 7715833
TI  - Different sensitivity of rat pineal N-acetyltransferase to alpha- and beta
      adrenergic receptor agonists during development: in vitro studies.
AB  - Herein, we investigate the mechanisms involved in the adrenergically mediated
      stimulation of rat pineal N-acetyltransferase (NAT) activity during development
      using an in vitro model. Compared with adults, results suggest a different
      regulation of pineal NAT activity in growing rats where a similar efficiency of
      alpha- and beta-adrenergic receptor agonists is observed during the 1st weeks of
      age for activating the enzyme. In adult rats, beta- but not alpha-adrenergic
      receptors appear to play the preeminent role. The results indicate that the
      adrenergic receptor agonists used acted in a non-specific manner by binding to
      relatively immature receptors early during development.

PMID- 7715835
TI  - New application of the Z estimator to identify the cognitive P300 in non-averaged
      human brain potentials.
AB  - Electronic averaging is currently used for displaying event-related potentials
      such as P300 from the electroencephalogram (EEG). However, there is a growing
      need for upgraded methods allowing cognitive components to be identified in
      single trial brain responses. The Z estimation method has been adapted for the
      topographic testing of non-averaged scalp recordings. Z values approximating +1
      help validate a genuine P300 while failure to pass the Z test may suggest the
      spurious nature of a late positivity that mimicks a P300. Z testing can also
      identify interference from transient EEG alpha activity by showing alternations
      between +1 and -1 values, as expected from an oscillating alpha generator. In
      contrast with previous methods based on EEG recordings from a single scalp site,
      our topographic Z method takes into account 28 scalp sites for single trials
      testing.

PMID- 7715836
TI  - Nerve growth factor levels in cultured human skin cells: effect of gestation and
      viral transformation.
AB  - Extracts of cultured human keratinocytes and fibroblasts were assayed for nerve
      growth factor-like immunoreactivity (NGF) by a specific enzyme-linked
      immunoabsorbant assay. NGF levels were higher in primary cultured keratinocytes
      than in freshly isolated keratinocytes or culture through multiple passages.
      Viral transformation of keratinocytes with the human papilloma virus (HPV16)
      significantly increased NGF levels, whilst transformation with the simian virus
      (SV40), which induces simple epithelial differentiation, reduced the
      concentration of NGF. Passaged epidermal keratinocytes contained more than twice
      as much NGF as did passaged fibroblasts. Oral keratinocytes and fibroblasts, and
      psoriatic fibroblasts, all from high turnover tissues, did not contain
      significantly different levels of NGF in culture than dermal keratinocytes or
      fibroblasts. Foetal fibroblasts contained five times as much NGF as did adult
      fibroblasts. These results suggest that basal keratinocytes are a major but not
      sole source of NGF in human skin, and that NGF may play a role in human skin
      development.

PMID- 7715834
TI  - Immunocytochemical localization of mu-opioid receptor in the rat caudate-putamen.
AB  - A guinea pig antibody against a C-terminal peptide of rat mu-opioid receptor
      (MOR) was produced to examine the distribution of MOR in the rat caudate-putamen
      (CP). The anti-peptide antibody recognized a protein of M(r) 69,000 in Triton X
      100 extract of rat brain and in the membrane fraction of MOR-expressing culture
      cells. Intense MOR-like immunoreactivity (LI) was observed in island-like areas
      of the CP. Some MOR-LI was located on the cell bodies and dendrites of CP
      neurons. Double immunofluorescence study revealed that the intensely MOR
      immunoreactive areas showed weak calbindin-LI, surrounded by intensely calbindin
      positive regions. The results indicate that MOR-LI is enriched in the 'patches'
      of the neostriatal mosaic compartmentation.

PMID- 7715837
TI  - Ultrastructural immunolocalization of muscarinic acetylcholine receptor in the
      dorsal thalamus of rat.
AB  - The ultrastructural distribution of muscarinic acetylcholine receptor (mAChR) in
      the dorsal thalamus of the adult rat was studied by means of pre-embedding
      immunocytochemistry using the monoclonal antibody M35. mAChR immunoreactivity
      (ir) was present with variable intensity in the different thalamic nuclei, but
      with a similar subcellular localization. Labeling was restricted to neuronal cell
      bodies and dendrites, where it was both in the cytoplasm and along the
      cytoplasmic side of the plasma membrane, in areas post-synaptic to small
      terminals with round clear vesicles but also in non-synaptic areas. Glial cells
      were unlabeled. By combining the pre-embedding immunostaining for mAChR with post
      embedding immunogold labeling for GABA it was shown that GABAergic terminals made
      synaptic contacts with cholinoceptive structures, but no mAChR ir was present at
      their post-synaptic sites.

PMID- 7715838
TI  - GTP- and GDP-analogues modulate an inwardly rectifying chloride channel in
      cultured hippocampal neurons.
AB  - Three different GABA-insensitive Cl- channels could be resolved in cultured
      hippocampal neurons using the inside-out patch clamp configuration. The most
      commonly observed channel revealed an inward rectification with a chord
      conductance of 40 pS in symmetrical Cl- solutions at a membrane potential of -50
      mV and had voltage sensitive gating kinetics. Channel openings were not observed
      in cell-attached patch, and after excision, several minutes of perfusion of the
      cytoplasmic side were required before detecting the first openings. The open
      state probability was increased by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma
      S 10(-4) M) and reduced by guanosine 5'-O-(2-thiophosphate) (GDP-beta-S 10(-4) M)
      suggesting its regulation by G proteins. This new identified chloride channel may
      account for the previously described voltage-sensitive, inward-rectifying whole
      cell Cl- current which was enhanced by adenosine in a pertussis toxin-sensitive
      manner.

PMID- 7715839
TI  - Fluoro nissl green: a novel fluorescent counterstain for neuroanatomy.
AB  - Fluorescent neuroanatomic techniques, such as immunofluorescence and retrograde
      and anterograde tracing studies, derive great utility from their specificity.
      However, the specificity can be a drawback as well, in that it may be difficult
      to assess labeled neurons or neural processes in their cytoarchitectonic context.
      We report the characteristics of a newly synthesized fluorescent counterstain,
      Fluoro Nissl Green (3,8-diamino-10H-quindoline) with spectral characteristics
      similar to fluorescein. This Nissl-like counterstain can be used as a green
      neuronal counterstain for red-emitting markers such as rhodamine and Di-I.

PMID- 7715840
TI  - The increase in morphine antinociceptive potency produced by carrageenan-induced
      hindpaw inflammation is blocked by naltrindole, a selective delta-opioid
      antagonist.
AB  - Carrageenan-induced inflammation of the rat hindpaw has been used as a model for
      persistent pain of inflammatory origin. The induction of inflammation resulting
      from carrageenan injection in the rat hindpaw has been shown to elicit an
      increase in the antinociceptive potency of morphine, an effect postulated to be
      related to reduced levels of spinal cholecystokinin (CCK). Recent findings have
      related the anti-opioid effect of CCK to a decrease in activation of delta-opioid
      receptors. For this reason, we have examined the effects of the delta-opioid
      antagonist naltrindole (NTI) on the modulation of morphine antinociceptive
      potency resulting from carrageenan-induced inflammation. Rats with carrageenan
      induced hindpaw inflammation received several doses of morphine in the absence or
      presence of NTI and were tested in the hot plate (HP) and tail flick (TF) tests.
      These results were compared to those of non-carrageenan injected rats. Morphine
      was significantly more potent in inflamed, than in control, rats in both tests.
      While NTI did not affect morphine antinociceptive potency in control rats in
      either test, this opioid delta antagonist blocked the increase in morphine
      potency resulting from carrageenan inflammation in nearly every case. The
      blockade of the enhancement of morphine potency was such that the effect of a
      given dose of morphine was similar in control rats and carrageenan-injected rats
      with NTI. We suggest that carrageenan-induced inflammation may alter endogenous
      enkephalin levels, perhaps by a decrease in CCK availability. The enhancement of
      morphine antinociceptive potency may result from the well-established synergism
      seen following the activation of opioid delta receptors by enkephalins.

PMID- 7715842
TI  - Pharmacological properties of recombinant N-methyl-D-aspartate (NMDA) receptors
      containing the epsilon 4 (NR2D) subunit.
AB  - The modulatory effects of spermine, histamine, and ifenprodil on recombinant N
      methyl-D-aspartate (NMDA) receptors expressed from the NR1A and epsilon 4 (NR2D)
      subunits were studied by voltage-clamp recording in Xenopus oocytes. Spermine had
      no effect on responses to glutamate and glycine at NR1A/epsilon 4 receptors. None
      of the four previously described effects of spermine, all of which are seen at
      NR1A receptors and at NR1A/NR2B receptors, was seen at NR1A/epsilon 4 receptors.
      Similarly, NR1A/epsilon 4 receptors were insensitive to potentiation by histamine
      and to blockade by ifenprodil. The properties of NR1A/epsilon 4 receptors thus
      resemble those of NR1A/NR2C receptors and are markedly different from those of
      homomeric NR1A receptors. In heteromeric NR1A/epsilon 4 receptors the epsilon 4
      subunit may alter properties associated with the NR1A subunit, as has been
      previously suggested for NR2A, NR2B, and NR2C subunits in NR1A/NR2 receptors.

PMID- 7715841
TI  - Early activation of arm muscles follows external perturbation of upright stance.
AB  - Grasping, counterbalancing and protective arm movements are an important defence
      against external postural perturbation, but are commonly constrained in studies
      of postural control. We measured muscle activity at the shoulder, and the lower
      leg, during unconstrained responses to platform translation. Results revealed
      very early activation in shoulder muscles, similar in timing to the 'automatic'
      ankle responses. The arm activation occurred even when the reaction provided no
      immediate defence against destabilization but would appear to be more than a
      'startle' response, since the activation was scaled to the perturbation magnitude
      and persisted even when perturbations were expected. The arm activation would
      appear to be driven from a remote sensory source, since there was negligible
      loading or stretch of the arm muscles.

PMID- 7715843
TI  - Electrical stimulation of the Gasserian ganglion induces structural alterations
      of calcitonin gene-related peptide-immunoreactive perivascular sensory nerve
      terminals in the rat cerebral dura mater: a possible model of migraine headache.
AB  - Calcitonin gene-related peptide (CGRP)-positive sensory nerve fibers in the rat
      supratentorial dura mater are equipped with varicosities and club-like nerve
      terminals, often attached to the walls of blood vessels. Brief electrical
      stimulation of the Gasserian ganglion results in significant swelling and
      increased immunohistochemical staining of ipsilateral perivascular club-like
      terminals, while long-lasting electrical stimulation induces their disintegration
      or bursting, resulting in irregular, corroded outlines of terminals and en
      passant beads. Stimulation-induced morphological alterations of perivascular
      terminals may represent a structural basis of increased CGRP content in jugular
      blood which follows electrical stimulation of the Gasserian ganglion and
      accompanies migraine attacks.

PMID- 7715845
TI  - The benzodiazepine receptor inverse agonist FG 7142 induces cholecystokinin gene
      expression in rat brain.
AB  - The effects of acute administration of the anxiogenic benzodiazepine receptor
      ligand, N-methyl-beta-carboline-3-carboxamide (FG 7142) and of a single exposure
      to the elevated plus-maze test of anxiety on preprocholecystokinin mRNA levels in
      rat brain were examined using the technique of in situ hybridisation.
      Administration of FG 7142 (10 mg/kg i.p.), but not elevated plus-maze exposure,
      increased cholecystokinin (CCK) mRNA levels in the basolateral amygdala and the
      CA3 pyramidal cell layer of the hippocampus. Neither stimulus produced changes in
      thalamic structures. These data suggest that drug-induced anxiety can induce CCK
      gene expression in brain structures previously implicated in anxiety.

PMID- 7715844
TI  - Vestibular and auditory influences on segmental motoneuron excitability--a
      comparative study.
AB  - This study aimed to investigate the vestibular and acoustic influences on
      segmental motoneuron excitability in the same normals in order to compare the
      effects of both sensory systems. The results show that both systems exert similar
      influences on H-reflex in the same subjects. These indicate similarities in the
      function of motor control and suggest common final pathways of the vestibular and
      auditory activity to the segmental motoneuron. The alternative effect,
      facilitation or inhibition, of acoustic and vestibular stimuli on H-reflex is
      devoted to processing of the labyrinthine activation in the brainstem reticular
      formation, or to the state of the spinal interneurons.

PMID- 7715846
TI  - Electrophysiological evidence for a direct neuronal connection from the motor
      cortex to the parietal association cortex of the cat.
AB  - Neuronal responses of the parietal association cortex to motor cortex stimulation
      were studied intracellularly in anaesthetized cats. Antidromic responses and
      monosynaptic excitatory postsynaptic potentials (EPSPs) of ipsilateral anterior
      suprasylvian and lateral gyri neurons have been established. Oligo- and
      polysynaptic EPSPs were also recorded. Some cells reacted with both antidromic
      and orthodromic excitation. It is concluded that, besides the well-known parietal
      to-motor cortex projection, there is also a reciprocal link from the motor cortex
      back to the parietal association cortex.

PMID- 7715847
TI  - Expression of NADPH-diaphorase in the rat forebrain during development.
AB  - Expression of NADPH-diaphorase (NADPH-d) was studied in the rat telencephalon and
      diencephalon from embryonic day 15 (E15) to postnatal day 30 (P30). The study has
      focused on the first appearance of NADPH-d staining in some areas which show high
      expression during adult life. The time of appearance ranged from E15 to the first
      days following birth, depending on the location of the cells. In many regions,
      neuronal processes, when staining appeared, were observed in close relationship
      with cerebral vessels. A possible role for nitric oxide in brain development
      should be explored.

PMID- 7715848
TI  - Effects of mercury on serotonin concentration in the brain of tilapia,
      Oreochromis mossambicus.
AB  - In order to know the effect of mercury pollution on the serotonergic system of
      fish, serotonin concentrations in a discrete brain region of tilapia, Oreochromis
      mossambicus, were examined. Serotonin concentration was measured using a high
      performance liquid chromatography system with electrochemical detector. In male
      fish, the concentrations of serotonin were 1.468 +/- 0.350, 0.811 +/- 0.190 and
      0.330 +/- 0.061 micrograms/g wet tissue in hypothalamus, telencephalon and optic
      lobe, respectively. The serotonin content was significantly different between
      each region; the hypothalamus had a higher content than that of the telencephalon
      and optic lobe. The serotonin concentration in female hypothalamus was 1.102 +/-
      0.112 micrograms/g wet tissue which was significantly lower than that in males.
      However, serotonin concentration in the telencephalon and optic lobe showed no
      difference between male and female. After exposure to 0.015 and 0.03 ppm HgCl2
      for 6 months beginning 7 days posthatching, male sample fish showed a
      significantly dose-dependent decrease in serotonin concentration in the
      hypothalamus. But a similar phenomenon was not found in other regions of the
      brain. These results suggest that exposure to HgCl2 results in an attenuated
      development of the serotonergic system in the hypothalamus of fish.

PMID- 7715849
TI  - Concentration and regional distribution of propofol in brain and spinal cord
      during propofol anesthesia in the rat.
AB  - We evaluated the pharmacokinetics and regional distribution of propofol in the
      brain and spinal cord during propofol anesthesia in Sprague-Dawley rats, using
      high-performance liquid chromatographic determination of propofol concentration
      in brain, whole blood and plasma. We found that the concentration of propofol in
      the brain increased and decreased expeditiously during and after a 15-min and 30
      min period of i.v. infusion of an anesthetic dose (60 mg/kg per h) of propofol.
      Furthermore, propofol was evenly distributed in the brain and spinal cord during
      infusion, with a significant inter-individual variation. Upon the establishment
      of anesthesia 15 and 30 min following intravenous infusion of propofol, the
      concentration of propofol in the brain, whole blood and plasma was respectively
      15.7 +/- 1.9 and 39.4 +/- 2.7 micrograms/g, 4.5 +/- 1.2 and 13.6 +/- 1.3
      micrograms/ml and 1.8 +/- 0.5 and 5.1 +/- 0.9 micrograms/ml (mean +/- SEM, n = 6
      or 7). These high brain/blood and brain/plasma ratios during anesthesia suggest
      that propofol manifests a pharmacokinetic profile that is different from at least
      thiopental.

PMID- 7715850
TI  - Effects of aluminum lactate on murine neuroblastoma cells.
AB  - Aluminum is the most abundant metal and the third most common element in the
      earth's crust. It's toxicity has emerged as one of the most serious complications
      in the treatment of chronic renal failure. Aluminum lactate [Al(lac)3], at
      concentrations less than those affecting cell viability (< 5 mM) decreased the
      capability of mouse neuroblastoma cells to incorporate 14C-leucine and 3H
      thymidine. This decreased capability to synthesize protein and DNA was
      accompanied by extension of neurites, increased capacity of the cells to take up
      silver stain, and decreased reactivity to antibodies against neurofilaments and
      to lectins that recognize cell surface carbohydrate residues. In conclusion,
      Allac3 should be considered as a marked cytostatic as well as a strong
      neuritogenic agent.

PMID- 7715851
TI  - 200 kDa and 160 kDa neurofilament protein phosphatase resistance following in
      vivo aluminum chloride exposure.
AB  - We have used time-course dephosphorylation experiments and two dimensional
      isoelectric focusing to assess the phosphorylation state of neurofilament (NF)
      proteins following the intracisternal inoculation of AlCl3. Littermates of New
      Zealand white rabbits, age 5-6 weeks, were inoculated with either 1000, 750, 500,
      250 or 100 micrograms AlCl3 in 0.9% NaCl or 0.9% NaCl alone, killed 48 hours
      later and the NF-enriched cytoskeletal fraction isolated from the spinal cord.
      Neurofilamentous inclusions did not occur following inoculums of 100 or 250
      micrograms AlCl3, but thereafter developed in increasing quantities in a dosage
      dependent manner. Incubation of the NF-enriched fraction with E. Coli. alkaline
      phosphatase (enzyme: substrate 1:50) induced a replacement of the highly
      phosphorylated 200 kDa isoform of NFH with a more poorly phosphorylated 170 kDa
      isoform, confirmed by immunoblot analysis. This reaction was complete within 20
      minutes with NF derived from NaCl, 100 or 250 micrograms AlCl3 inoculated rabbits
      and within 30 minutes for 500 micrograms AlCl3 inoculums. However, residual
      highly phosphorylated NFH isoforms persisted at 60 minutes for 750 micrograms
      inoculums and 90 minutes for that derived from 1000 micrograms AlCl3 inoculums. A
      similar inhibition of phosphatase activity was observed for NFM. Following two
      dimensional electrophoresis of the NF-enriched isolate, no alteration in the net
      phosphorylation state of individual NF subunit proteins was observed--regardless
      of the inoculum. These results demonstrate a dose-dependent induction of
      neurofilamentous inclusions in spinal motor neurons following intracisternal
      AlCl3 inoculation accompanied by increasing phosphatase resistance without a
      demonstrable alteration in NF net phosphorylation state.

PMID- 7715852
TI  - The effects of Aroclor 1254 on undifferentiated and NGF-stimulated
      differentiating PC12 cells.
AB  - Rat pheochromocytoma [PC12] cells were used as models of a dopaminergic system to
      examine the effects of subchronic exposure to Aroclor 1254 on levels of cellular
      dopamine in undifferentiated and nerve growth factor (NGF)-stimulated
      differentiating cells. Either in the absence, or simultaneously in the presence
      of NGF, exposure to Aroclor 1254 resulted in dose-dependent decreases in levels
      of cellular dopamine, which with increasing time of exposure, up to 3 days,
      became increasingly sensitive to lower concentrations of PCBs as evidenced by
      shifts of the dose-response curves to the left. Pretreatment of PC12 cells with
      NGF for 7 or 14 days prior to exposure to Aroclor 1254 afforded partial
      protection from the PCB-mediated decreases in cellular dopamine, consistent with
      the hypothesis that the cells have different sensitivities to the dopamine
      decreasing effects of PCBs, depending on the state of differentiation that they
      are in when exposure to PCBs occurs. Exposure to Aroclor 1254 did not block the
      morphological aspects of NGF-induced neuronal differentiation, but rather
      enhanced the NGF-stimulated elongation of neurites in a dose-dependent manner.
      These results suggest that Aroclor 1254 reduces the levels of cellular dopamine,
      in both undifferentiated and differentiating PC12 cells, and that pretreatment
      with NGF may partially prevent PCB-mediated decreases in cellular dopamine. These
      results also suggest that Aroclor 1254 may enhance neurite elongation.

PMID- 7715853
TI  - Effects of repeated administrations of EGF and TGF-alpha on mouse neurobehavioral
      development.
AB  - In this study we tested the effects of repeated administrations of Epidermal
      Growth Factor (EGF) and Transforming Growth Factor-alpha (TGF-alpha) on mouse
      pups' neurobehavioral development. Each subject was injected subcutaneously with
      either EGF or TGF-alpha on postnatal days 2, 4, 6, 8, and 10. Pups treated with
      these two peptides showed accelerated eyelid opening and eruption of the lower
      incisors when compared to Cytochrome c-injected control littermates. EGF, but not
      TGF-alpha, resulted in a slight body growth retardation. When scored for a number
      of neurobehavioral parameters, EGF pups showed a delayed appearance of the
      righting reflex. Also, EGF-treated pups exhibited greater ultrasonic vocalization
      calling rates than controls when tested on postnatal day 7. Overall, TGF-alpha
      administration resulted in minor effects, when compared with EGF treatment,
      probably as a result of the lower dose administered (EGF: 3.5 mg/kg vs TGF-alpha:
      1 mg/kg). TGF-alpha affected pups' eyelid opening and incisor eruption, similarly
      to EGF, but seemed to exert an opposite effect on some neurobehavioral scores, in
      line with what was already reported for Nerve Growth Factor (NGF) (Calamandrei
      and Alleva, 1989). These results confirm the role played by polypeptide growth
      factors on mammalian physical and neurobehavioral development and suggest that
      TGF-alpha might affect mouse brain development in a similar fashion as NGF.

PMID- 7715854
TI  - Effects of acute and continuous ozone (O3) exposure on activity/exploration and
      social behavior of CD-1 mice.
AB  - This study was aimed at investigating the behavioral effects of ozone (O3)
      exposure in CD-1 mice. Pairs of same-sex adult male and female mice were
      continuously exposed for 13 days to either 0, 0.4, 0.8, or 1.2 ppm O3. The
      exposure apparatus consisted of a system for O3 production and delivery into four
      stainless-steel chambers, each equipped to contain up to 24 home cages, with
      continuous monitoring and recording of concentrations. Acute behavioral changes
      were assessed during the first hour of O3 exposure without removing animals from
      the chambers. The onset of exposure produced remarkable behavioral disturbances
      consisting of a sharp increase of several responses (rearing, sniffing, grooming,
      feeding, and social interactions) paralleled by a reduction of bar-holding. These
      changes were rapidly reversed within 1 hour, suggesting that they constituted a
      response to strong novel stimulation followed by habituation. Subsequently, brief
      sessions of videorecording of the animals' activities in freshly cleaned cages
      (identical to the home cages) were performed outside the chambers after 3, 7, and
      10 days of exposure. These tests showed a significant concentration-dependent
      increase of grooming and rearing and a decrease of crossing and wall climbing.
      Both food and water intake showed a nonmonotonic trend over time consisting of a
      concentration-dependent depression (for about 3 and 7 days, respectively)
      followed by recovery; body weight followed a similar trend. The detailed study of
      various components of the animal's behavioral repertoire, showing concentration
      dependent and time-dependent changes in different directions, appears to be a
      sensitive tool in the analysis of pollutants' effects.

PMID- 7715855
TI  - Anticonvulsant and antilethal effects of the phencyclidine derivative TCP in
      soman poisoning.
AB  - The protection afforded by TCP (thienylcylohexylpiperidine), a non-competitive
      blocker of N-methyl-D-aspartate (NMDA) receptors, against the seizures and
      lethality produced by 2 x LD50 of soman (62 micrograms/kg, sc), an irreversible
      inhibitor of cholinesterase, was studied in guinea-pigs. In the presence of
      additional anticholinergic medication (pyridostigmine: 0.2 mg/kg, sc, 30min prior
      to soman; atropine sulphate: 5mg/kg, im, 1 min post-soman), TCP pretreatment
      (2.5mg/kg, im, 30 or 15 min prior to soman) did not generally prevent the
      appearance of soman-induced status epilepticus but did arrest it after 30-40 min
      in 80% (TCP-30min) or 100% (TCP-15min) of the convulsing subjects. Moreover, in
      all subjects treated curatively, TCP was able to interrupt ongoing status
      epilepticus in approximately 20, 10 or 8 min when it was administered 5, 30 or
      60min respectively after the onset of epileptiform tracings on EEG. All of these
      curatively administered animals survived and recovered remarkably well. On every
      criteria examined (latency-to-seizure arrest, 24hr-survival rate, clinical
      recovery), injection of 2.5mg/kg TCP after 90min of seizures appeared slightly
      less efficient compared to earlier curative administration. Therefore, our study
      (a) establishes that the previously reported capacity of MK-801
      (dibenzocyclohepneimine) to counteract soman toxicity is not unique and could be
      extended to other non-competitive inhibitors of NMDA receptors; (b) shows that
      TCP could easily prevent and, above all, interrupt soman-induced seizures;
      furthermore, TCP appears the first compound ever tested on soman poisoning that
      still displays satisfactory anticonvulsant activity after such a long duration of
      initial status epilepticus (90min); therefore, TCP might be of special value for
      the delayed therapy for soman poisoning; (c) confirms that NMDA receptors are
      involved in the maintenance of seizures and play an important role in other
      processes implicated in the overall toxicity (including the lethal respiratory
      effects) of soman poisoning.

PMID- 7715856
TI  - Time course of postnatal lead-induced changes in dopamine receptors and their
      relationship to changes in dopamine sensitivity.
AB  - Although alterations in dopaminergic function represent a potential neurochemical
      basis of Pb-induced behavioral deficits, the impact of postnatal Pb exposure on
      DA systems has not been adequately delineated. This study examined the effects of
      postnatal Pb exposure, across a broad range of concentrations, on the ontogeny of
      both D1 and D2 DA (dopamine) receptors in striatum and nucleus accumbens. Rat
      pups were exposed to Pb from 0-21 days of age via lactating dams consuming
      solutions of 0, 100, 350, 1000 or 2000 ppm Pb acetate. Pups were sacrificed for
      homogenate receptor binding assays at 7, 14, 21 or 60 days of age. Postnatal Pb
      exposure generally facilitated DA receptor number (Bmax) development over the
      first 21 days of age, in both striatum and nucleus accumbens, without any
      apparent effects on receptor affinity (Kd values). Residual changes in Bmax were
      found for both D1 and D2 receptors at 60 days of age, with Bmax changes occurring
      in opposite directions in the two brain regions. D1 Bmax values were increased in
      striatum, and decreased in nucleus accumbens at PbB (blood lead levels) of > 50
      ug/dl, whereas, at PbBs of 10-20 ug/dl, but not higher, D2 Bmax values were
      decreased in striatum but increased in nucleus accumbens. These findings suggest
      a preferential vulnerability of D2 receptors to lower Pb exposure concentrations
      and underscore the importance of Pb exposure level and brain region to resulting
      receptor changes. A linear relationship was observed between changes in nucleus
      accumbens D2 receptor Bmax values and Pb-induced changes in D2 sensitivity as
      derived from a drug discrimination study using littermates of offspring from the
      current study (Cory-Slechta et al., 1992), suggesting nucleus accumbens as a
      preferential site of Pb-induced D2-mediated effects.

PMID- 7715857
TI  - Changes in autonomic function as determined by ECG R-R interval variability in
      sandal, shoe and leather workers exposed to n-hexane, xylene and toluene.
AB  - To clarify if autonomic nervous system effects might be associated with exposure
      to organic solvents, 30 sandal, shoe and leather workers exposed to n-hexane,
      xylene, and toluene, and 25 unexposed controls were examined using the
      coefficient of variation in electrocardiographic R-R intervals (CVRR), combined
      with the distribution of nerve conduction velocities (DCV). The C-CVRSA and C
      CVMWSA (two component CVs of the CVRR reflecting parasympathetic and sympathetic
      activities, respectively) were also computed from component spectral powers using
      autoregressive spectral and component analyses. Concentrations of the metabolites
      of the solvents in urine samples taken in the morning before work were 0-3.18
      (mean 1.39) mg/l for 2,5-hexanedione, 0.10-0.43 (mean 0.19) g/g creatinine (Cn)
      for methylhippuric acid, and 0.05-2.53 (mean 0.41) g/g Cn for hippuric acid. In
      the solvent workers, the CVRR and C-CVRSA were reduced significantly when
      compared with the unexposed controls. The faster velocities of the DCV as well as
      the sensory median nerve conduction velocity (SCV) were significantly slowed in
      the solvent-exposed workers. The SCV was significantly correlated with the CVRR
      and C-CVMWSA among the solvent workers. These data suggest that chronic exposure
      to some organic solvents may affect cardiac autonomic function (mainly,
      parasympathetic activity) in addition to faster myelinated fibers of the
      peripheral nerves. However, the absence of significant dose-effect relations
      among the solvent workers makes it difficult to definitively attribute the
      differences to specific solvent exposures.

PMID- 7715858
TI  - Carbon dioxide potentiates the mitogenic effects of nicotine and its carcinogenic
      derivative, NNK, in normal and neoplastic neuroendocrine lung cells via
      stimulation of autocrine and protein kinase C-dependent mitogenic pathways.
AB  - It has been shown that chronic lung diseases which increase the concentration of
      pulmonary carbon dioxide (CO2) at the expense of oxygen stimulate the secretion
      of biogenic amines and neuropeptides by pulmonary neuroendocrine cells (PNE
      cells) in man and laboratory animals. This increase in secretory activity is
      always accompanied by hyperplasia of PNE cells, and smokers with chronic
      obstructive lung disease are at high risk for the development of neuroendocrine
      lung cancer. We have previously shown that nicotine and the structurally related
      nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), stimulate the
      proliferation of neuroendocrine cell lines derived from lung carcinoid tumors via
      interaction with nicotinic acetylcholine receptors (nAChR). In our current
      experiment, we have addressed the mechanisms of cell proliferation in response to
      nicotine and NNK in normal PNE cells derived from fetal hamster lungs, and two
      cell lines derived from human neuroendocrine lung cancers. Our data show that in
      these systems the mitogenic effects of nicotine and NNK are potentiated in a
      concentration-dependent manner by elevated levels of CO2, an effect blocked by
      inhibitors of protein kinase C(PKC) and reduced by antagonists of receptors for 5
      hydroxytryptamine (5-HT, serotonin) and mammalian bombesin. The observed effects
      of CO2 were saturable and independent of changes in the acidity of the tissue
      culture media. Our data suggest that increases in CO2 concentration at the
      expense of oxygen may stimulate signal transduction pathways in normal and
      neoplastic neuroendocrine lung cells thus enhancing their susceptibility to the
      mitogenic effects of tobacco-specific toxicants.

PMID- 7715860
TI  - Changes of activity and ultrastructural localization of alkaline phosphatase in
      cerebral cortical microvessels of rat after single intraperitoneal administration
      of mercuric chloride.
AB  - Inorganic mercury salts administered systemically at low mg/ml doses produce
      neurotoxic effects without penetrating the cerebral microvascular endothelial
      cells which form the blood-brain barrier (BBB). This phenomenon promoted
      investigations testing a hypothesis relating inorganic mercury-induced brain
      dysfunction to its interference with the BBB transport. In the present study, we
      tested the effect of a single i.p. administration of mercuric chloride (MC) (6
      mg/kg body weight) on the activity and ultrastructural localization of cerebral
      alkaline phosphatase (AP), a cerebromicrovascular marker enzyme primarily located
      on luminal plasmalemma of endothelial cells. At 1h after MC administration, light
      microscopy revealed a virtual absence of AP in cerebral cortical layers II and
      III, and its dramatic reduction in the remaining layers. Electron microscopy
      confirmed the disappearance of the AP reaction product from luminal endothelial
      cell membranes, and luminal phasmalemma revealed pinocytic vesicles and
      invaginations likely to manifest changes in BBB transport. At 18h post-treatment,
      a moderate enzyme activity appeared on abluminal endothelial plasmalemma and on
      basement membrane, but remained absent from luminal plasmalemma. A similar
      picture persisted through day 5 post-treatment. The inhibition and subsequent
      translocation of AP activity from luminal to abluminal site and the accompanying
      ultrastructural changes are typical of the formation of "leaky" microvessels,
      previously reported for a variety of neuropathological conditions associated with
      BBB damage.

PMID- 7715859
TI  - Interaction of cyanide with a dopamine metabolite: formation of a cyanohydrin
      adduct and its implications for cyanide-induced neurotoxicity.
AB  - Incubation of rat pheochromocytoma (PC12) cells with cyanide (1-10 mM) for 30 min
      produced a compound which eluted between dopamine (DA) and 3,4
      dihydroxyphenylacetic acid in HPLC-EC analysis. Generation of the compound was
      rapid, concentration-dependent and blocked by pretreatment with clorgyline, a
      monoamine oxidase A inhibitor. In cell free incubation, the compound formed
      rapidly when cyanide was added to a mixture of monoamine oxidase and DA, but was
      not detected when cyanide was included with DA alone. The compound was
      radiolabelled when 14C-KCN was added to the incubation mixture. Based on these
      results, it is proposed that the deaminated metabolite of DA, 3,4
      dihydroxyphenylacetaldehyde (DOPAL), reacts non enzymatically with cyanide to
      form the cyanohydrin adduct 2-hydroxy-3-(3,4-dihydroxyphenyl) propionitrile
      (HPN). HPN was confirmed by spectral analysis and co-elution with synthetic HPN.
      Incubation of mouse brain slices with cyanide (1 mM) generated 0.98 ng HPN/100 mg
      wet wt. over a 10 min period and HPN was detected in brains of mice after
      injection of cyanide (15.6 micrograms) into the lateral brain ventricle. Repeated
      doses of KCN (6 mg/kg, s.c., five times) produced 0.14 +/- 0.03 ng/100 mg of
      tissue in striatum. Incubation of PC12 cells for 60 min with 500 microM HPN
      killed 23% of the cells and increased DA release from the cells by 39.8% over
      untreated cells. Uptake of HPN into the cells was partially blocked by the
      catecholamine uptake inhibitor imipramine. These results indicate cyanide reacts
      with the DA metabolite DOPAL to generate a biologically active cyanohydrin adduct
      which may contribute to the neurotoxic response to cyanide.

PMID- 7715861
TI  - Modulation of developmental cerebellar ornithine decarboxylase activity by lead
      acetate.
AB  - The developing brain is particularly susceptible to the neurotoxic effects of
      lead exposure. The ontological profile of ornithine decarboxylase (ODC) activity
      in the cerebellum was examined following lactational exposure of rats to 0.2%
      lead acetate (Pb). Relative to controls, Pb-exposure induced ODC activity levels
      in a transient manner with a 50% increase at postnatal day (PND) 6, a 20%
      increase at PND 9, returning to control basal levels by PND 15. These effects
      were seen at exposure levels of Pb that did not alter the normal growth and body
      weight of either the lactating dam or the developing pups. Basal cerebellar ODC
      activity in homogenates was increased with addition of low concentrations of Pb
      acetate (0.01 microM and 0.1 microM), while concentrations of 1 microM or greater
      were inhibitory. The effects of Pb acetate on tissue ODC activity in vitro were
      not mimicked by the addition of calcium chloride. Unlike tissue ODC activity,
      incubation of these metals with a pure ODC protein preparation exhibited
      fluctuations in ODC activity possibly due to the ionic interactions of Pb or
      calcium chloride. Calcium homeostatic mechanisms appeared to be unchanged with Pb
      exposure, at this dose, in that neither 45Ca-uptake (both mitochondrial and
      microsomal) nor synaptosomal Ca(2+)-ATPase activity was altered. These data
      suggest that alterations in ODC activity may be indicative of subtle toxicant
      induced perturbations during early development. Although the precise mechanism by
      which Pb may induce ODC activity in developing tissue is unknown, our results
      suggest that Pb may specifically alter ODC activity via cytosolic interactions.

PMID- 7715863
TI  - Disruption of Schwann cell elemental composition is not a primary neurotoxic
      effect of 2,5-hexanedione.
AB  - The effects of 2,5-hexanedione (2,5-HD) on elemental composition (Na, P, S, Cl,
      K, Ca, Mg) and water content of Schwann cells and myelin were assessed in rat
      posterior tibial and proximal sciatic nerves. Animals were intoxicated with 2,5
      HD by two routes of administration: oral (0.4% in drinking water for 78, 85 or
      104 days) and intraperitoneal (i.p.; 0.4 gm/kg/day x 11, 18 or 30 days). Electron
      probe X-ray microanalysis demonstrated that oral 2,5-HD intoxication produced
      temporally-dependent disruptions of Na, P, Cl, K and Mg distributions in Schwann
      cells of proximal and distal nerve regions. On both a dry and wet weight basis,
      cytoplasmic Na and Cl concentrations increased, while P, K and Mg levels declined
      relative to control values. In contrast, intraperitoneal administration was
      associated with minimal changes in regional glial cell elemental concentrations.
      Moreover, neither route of intoxication altered the elemental composition nor
      water content of myelin. Thus, oral but not i.p. intoxication of rats with 2,5-HD
      causes perturbation of elemental distributions in peripheral nerve Schwann cells.
      Although the pattern of elemental disruption caused by oral administration is
      typical of cellular injury, the route-dependent nature draws into question the
      overall mechanistic relevance of this effect.

PMID- 7715862
TI  - Assessment of the role of dopaminergic systems in lead-induced learning
      impairments using a repeated acquisition and performance baseline.
AB  - This study assessed the possibility that changes in dopaminergic function might
      underlie Pb-induced learning impairments. If so, dopaminergic compounds might be
      expected to produce differential changes in learning accuracy in control vs. Pb
      exposed rats. Therefore, the effects on a multiple schedule of repeated
      acquisition and performance resulting from acute administration of the D1 agonist
      SKF38393 (3.0-9.0 mg/kg), the D2 agonist quinpirole (.025-.10 mg/kg), and the
      catecholamine depleter alpha-methyl-paratyrosine (AMPT; 50-100 mg/kg) were
      compared in control rats and rats chronically exposed to either 50 or 250 ppm Pb
      acetate in drinking water from weaning. This schedule required completion of a
      sequence of 3 responses for reinforcement, with the correct sequence for the
      learning (RA; repeated acquisition) component changing with each successive
      session, while the performance (P) component sequence remained constant across
      sessions. Quinpirole and AMPT showed a somewhat similar pattern of effects: both
      produced a more pronounced impairment of accuracy in the learning component as
      compared to the performance component of the schedule, and both decreased RA
      accuracy primarily by increasing the frequency of skipping errors. In contrast,
      SKF38393 decreased accuracy equivalently in both the RA and P components of the
      schedule and decreased RA accuracy primarily by increasing the frequency of
      perseverative errors. There were, however, no differential effects of these drugs
      on either accuracy or response rate in the Pb-treated group as compared to
      controls, providing little support, at least on the basis of this approach, for
      an involvement of dopamine sensitivity changes in lead-induced learning
      impairments.

PMID- 7715864
TI  - Toward the prevention of coronary heart disease: screening of children and
      adolescents for high blood cholesterol.
AB  - Coronary heart disease (CHD) remains the number one killer in the United States.
      This article summarizes the recommendations for cholesterol screening of children
      and adolescents by the American Academy of Pediatrics and the Expert Panel on
      Blood Cholesterol Levels in Children and Adolescents. Screening of children and
      adolescents is selective, and the determination to screen is based on past
      medical, family health, and health behavior histories. Children or adolescents
      with a family history of peripheral vascular disease or coronary artery disease
      in primary relatives under 55 years of age, or parents with high blood
      cholesterol levels, are considered to be at risk for high blood cholesterol and
      in need of screening. Children or adolescents who are obese, inactive, have
      hypertension or diabetes, or who smoke are also considered to be at risk. A
      universal approach to the prevention of CHD through diet and lifestyle is also
      described.

PMID- 7715865
TI  - Effective management of urinary discomfort.
AB  - Urinary discomfort is the second most common physical complaint affecting women.
      Although urinary discomfort is commonly a result of inflammation due to bacterial
      invasion, there are also nonbacterial causes. The development of antimicrobial
      resistance to bacteria is frequent and costs the patient and the medical
      community unnecessary time and money. Antimicrobial intervention should be
      instituted only after the uropathogen is identified through a urine culture.
      While awaiting the results of the urine culture or other laboratory or
      radiological tests, the patient's symptoms can be relieved with the use of
      urinary analgesics or antispasmodics. This conservative approach meets the
      immediate concern of the patient and better ensures a proper diagnostic workup
      and successful cure. Along with a conservative diagnostic approach, the patient
      should be included in all aspects of health care management.

PMID- 7715866
TI  - Recurrent urinary tract infections in otherwise healthy adult women. Rational
      strategies for work-up and management.
AB  - Recurrent urinary tract infections (UTIs) are common, but clinicians unfamiliar
      with the natural history or pathogenesis may order unnecessarily expensive tests
      and provide unsubstantiated advice to their patients. A large body of literature
      indicates that recurrent UTIs do not progress to permanent kidney damage or end
      stage renal disease. The vast number of UTIs are due to the interplay between
      minor weaknesses in host defenses and bacterial virulence factors. Sexual
      intercourse and diaphragm/spermicide use are the two behavioral factors most
      consistently associated with UTIs. Basic history, physical exam, and urinalysis
      are able to identify the few patients likely to benefit from invasive urologic
      workups, which usually have a very low yield when ordered routinely. Effective
      management options include daily or post-coital antimicrobial prophylaxis, or
      patient-initiated treatment. Patients can be reassured of an excellent prognosis.
      There is no evidence validating proscription of personal preferences, such as
      soda pop, tight clothing, or direction of perineal cleansing after defecation.

PMID- 7715867
TI  - Sexually transmitted diseases and HIV infection.

PMID- 7715869
TI  - Acceptance of nurse practitioner services by rural elderly.

PMID- 7715870
TI  - Evaluation and treatment of urinary incontinence: a primary care approach.
AB  - Of the approximate 10 million Americans affected by urinary incontinence, it is
      estimated that, when diagnosed and evaluated appropriately, 80% will respond to
      treatment. Primary care providers are in ideal positions to initially screen
      their patients for symptoms of urinary incontinence. In many situations, the
      primary care provider can also diagnose and successfully treat urinary
      incontinence as part of routine health care.

PMID- 7715868
TI  - The prevalence of advance directives: lessons from a nursing home.
AB  - This study of an elderly population examined the prevalence of advance
      directives, the barriers to documentation, and the relation of anxiety to advance
      directives. Elders (mean age 77.7 years) residing in a nursing home comprised the
      convenience sample (n = 104). Data were obtained by record review for the total
      sample, and personal interviews with 17 residents. Descriptive statistics and the
      chi 2-test of proportions were employed for analysis. The prevalence of
      documentation was 51.9% (n = 104), including 35 do-not-resuscitate orders, 17
      health care powers of attorney, 16 medical directives, and 13 living wills; 18
      records contained more than one directive. Those interviewed, both with and
      without advance directives, revealed low death anxiety (Templer's Death Anxiety
      Scale) reminiscing freely about their lives and experiences. Barriers suggested
      by the self-reports were misconceptions, little knowledge, opportunity, or
      interest in preparing directives, and the belief that clinicians or family were
      responsible for end-of-life decisions.

PMID- 7715871
TI  - Dietary compliance for patients with renal disease.

PMID- 7715872
TI  - Treatment of chronic hepatitis C with interferon alpha.
AB  - AIM: To evaluate the response to interferon alpha in patients with chronic
      hepatitis C in Christchurch. METHOD: Fifteen patients with chronic HCV were given
      interferon alpha 3 million units subcutaneously three times a week for up to 24
      weeks. A complete and partial biochemical response was defined by relative
      changes in the serum alanine aminotransferase (ALT) during the treatment period.
      Detection of HCV RNA by the polymerase chain reaction was used to determine the
      virological response to treatment. RESULT: A complete or partial response was
      seen in nine of the 15 patients (60%). Histological improvement was demonstrated
      in all patients for whom paired liver biopsies were taken. Following treatment
      two of the five complete responders have shown a sustained biochemical response
      but only one has remained PCR negative, ie, a sustained virological responder.
      The other three, complete responders and all four partial responders relapsed.
      CONCLUSION: The response to treatment and relapse was comparable with other
      studies. It remains to be shown whether investigation of the viral titre and/or
      viral type will help to explain the high relapse rate in these patients with
      chronic HCV.

PMID- 7715873
TI  - Hepatitis C prevalence and needle/syringe sharing behaviours in recent onset
      injecting drug users.
AB  - AIM: To investigate the prevalence of hepatitis C antibody (anti-HCV) in
      injecting drug users (IDU), particularly amongst those of recent onset beginning
      since the advent of the needle-exchange programme. Secondly this study sought
      information on needle-sharing practices. METHODS: The records of injecting drug
      users over 2 years from January 1992 were examined for anti-HCV results and
      needle-sharing reports on initial assessment at the Wellington drug dependency
      clinic. RESULTS: Amongst 110 injecting drug users 92 (84%) were tested for anti
      HCV, and 71 (77%) were positive. There was a significant (p = 0.02) association
      between the reported duration of intravenous drug misuse and the proportion of
      injecting drug users who were positive for anti-HCV. Of those injecting drug
      users who had reported use of less than 4 years, since the introduction of the
      New Zealand needle exchange programme, 53% were positive for anti-HCV. Needle
      sharing was frequently reported to have ever occurred in 74% of these patients at
      some time, and in 64% of those who reported use of less than 4 years. These
      differences were not significant. However, in the period before presenting 67%
      had not shared over the last 3 months and 57% had not shared over the previous 1
      year, which are improvements on previous studies of needle-sharing, considered to
      be the most important mode of transmission for blood-borne viruses in injecting
      drug users. CONCLUSIONS: These results suggest considerable potential for HIV
      infection rates among injecting drug users in New Zealand to increase from the
      current low level. There needs to be continuing emphasis on public health
      programmes to eradicate needle-sharing, and to promote safe injecting techniques
      for injecting drug users.

PMID- 7715875
TI  - Smoking at the end of pregnancy measured by cord blood cotinine assay.

PMID- 7715874
TI  - Foot care among diabetic patients in south Auckland.
AB  - AIM: To describe footcare among diabetic patients in south Auckland. METHOD:
      Direct interview of 331 European, 86 Maori and 123 Pacific Islands patients
      attending local diabetes services and a stratified subsample of general
      practitioners. Interviews included closed and open questions of diabetes
      knowledge, demographic and medical history and were followed by a thorough
      inspection of the feet. RESULTS: Major lesions (amputation, foot ulcer) and
      predisposing lesions (callus or fungal infection/maceration) were present in
      48.5% of patients. Major lesions were particularly common among Pacific Islands
      patients (9.4%) vs European (3.9%), Maori (5.5%), (p < 0.05). Fungal
      infection/maceration was less common among Pacific Islands patients (23.0%) vs
      42.3%, 42.2% respectively, (p < 0.001). Fungal infection/maceration was more
      common and callus formation less common among men when compared with women. Forty
      percent (n = 214) of patients, including eight with either an ulcer or a blister,
      had not had their feet examined over the preceding 12 months. Good foot care was
      present in 52.7% Europeans, 31.0% Maori and 26.8% Pacific Islands patients (p <
      0.001). Diabetes knowledge was poorest in those with poor foot care among
      Europeans and Maori. CONCLUSION: While the provision of footcare advice,
      adherence to such advice and monitoring of footcare remain uneven, the hospital
      and community costs of the diabetic foot will continue to be high.

PMID- 7715876
TI  - An unusual presentation of complete androgen insensitivity syndrome in general
      practice.

PMID- 7715877
TI  - DSAC seminars on recovery from the effects of sexual abuse.

PMID- 7715878
TI  - False authorship.

PMID- 7715879
TI  - Guidelines of the use of expensive medicines.

PMID- 7715880
TI  - Ottawa ankle rules for radiography of acute injuries.

PMID- 7715881
TI  - Bed sharing and cot death.

PMID- 7715882
TI  - Use of molecular typing to identify a nosocomial-acquired Campylobacter
      infection.

PMID- 7715883
TI  - Allergic reaction to pseudoephedrine.

PMID- 7715884
TI  - Trauma system coordination in New Zealand: a year of progress.

PMID- 7715885
TI  - The effects of privet exposure on asthma morbidity.
AB  - AIM: To determine whether privet may be an important cause of asthma morbidity.
      METHODS: The study was conducted in two parts; (1) a longitudinal study of asthma
      symptoms, medication use, peak expiratory flow rate and airway responsiveness
      during and after the privet-flowering season, and (2) bronchial challenge of 17
      subjects with two species of flowering privet. Subjects were asthmatics who
      attributed worsening asthma symptoms to privet exposure. All subjects were atopic
      and had perennial asthma symptoms requiring treatment with inhaled steroids and
      beta agonists. RESULTS: 1. Twenty subjects completed the longitudinal study.
      Airway responsiveness (PD20 histamine) was significantly greater during the
      privet-flowering season (0.4 mumol vs 0.73 mumol, p < 0.05). Symptom scores and
      bronchodilator use were higher and peak expiratory flow rates lower during the
      privet-flowering season, but the changes were small and not statistically
      significant. 2. Seventeen subjects from the longitudinal study subsequently had
      bronchial challenge studies performed. There were no isolated early responses,
      but six had late asthmatic responses. Eleven had no airway constrictor response
      to challenge with either of the two local varieties of privet. CONCLUSION:
      Although significant increases in airway responsiveness occur during the privet
      flowering season, only a proportion of this highly select group had a constrictor
      response to direct challenge. Privet exposure may cause bronchoconstriction in
      certain individuals, but it is unlikely to be responsible for a large proportion
      of asthma morbidity in New Zealand.

PMID- 7715886
TI  - An audit of the sudden infant death syndrome prevention programme in the Auckland
      region.
AB  - AIM: An audit of the sudden infant death syndrome (SIDS) prevention programme in
      the Auckland region. METHODS: 107 health professionals working in antenatal
      classes, postnatal wards, domiciliary midwifery and the Plunket Society were
      interviewed. RESULTS: Maternal smoking and infant sleeping position were
      considered to be the most important risk factors for SIDS; lack of breast feeding
      and cosleeping were rated less important. Many other putative risk factors were
      also mentioned. There was no difference in the evaluation of the relative
      importance of risk factors for SIDS by health professionals working in south
      Auckland, where SIDS mortality has declined only slightly, compared with the
      evaluation by health professionals in the rest of Auckland, where SIDS mortality
      has declined considerably. The most important source of information for health
      professionals was the pamphlet "Cot death: you can reduce the risks", which is
      designed for parents. CONCLUSION: Differences in the SIDS prevention message by
      health professionals do not explain differences in SIDS mortality within
      Auckland. Health professionals were knowledgeable about risk factors for SIDS,
      but knowledge could be improved further by regular updates. New resource material
      including posters and pamphlets for families is also required.

PMID- 7715888
TI  - A response to 'Nuclear medicine and radiology: a personal view'.

PMID- 7715887
TI  - On-call nuclear medicine service.

PMID- 7715889
TI  - Relationship between the OIH and 99Tcm-EC clearances.

PMID- 7715890
TI  - Assessment of myocardial viability: where are we?

PMID- 7715893
TI  - The importance of the perfusion index in the evaluation of captopril renography
      for transplant renal artery stenosis.
AB  - Severe renal artery stenosis (RAS) is a relatively uncommon complication
      following renal transplantation but is a curable cause of hypertension which
      demands reliable early diagnosis to reduce morbidity, mortality and graft loss.
      Captopril renography has been used for a number of years as a method of detecting
      RAS mainly in native kidneys, with only a few studies concerning the transplant
      situation. Controversy still exists as to the diagnostic accuracy of this test
      and as to the most appropriate interpretation criteria with which to establish a
      positive result. This paper reports the evaluation of 26 captopril renography
      investigations on hypertensive renal transplant patients with a suspected
      diagnosis of RAS. Each renogram study was correlated with an arteriogram as the
      'gold standard' which was undertaken within 28 days of the renography. A
      sensitivity of 92%, a specificity of 86% and an accuracy of 88% were achieved by
      including a consideration of the change in perfusion to the kidney between pre-
      and post-challenge studies. It is concluded that captopril renography is a useful
      screening test for the detection of transplant renal artery stenosis (TRAS).

PMID- 7715891
TI  - Identification of reversible ischaemia after acute myocardial infarction using
      thallium tomography with early and delayed imaging after resting injection.
AB  - We studied 30 patients 6 weeks after first myocardial infarction in order to
      compare early and delayed imaging after resting injection of thallium for the
      detection of viable myocardium. Twenty-six of the 30 patients studied had
      received thrombolysis. Conventional stress and redistribution thallium tomography
      was followed by a resting injection of thallium with imaging immediately after in
      all patients and 3 h later in a subgroup of 15 patients. Thallium uptake was
      graded semi-quantitatively in each of nine myocardial segments. Eighty-eight of
      the 270 segments had a fixed defect on redistribution imaging, 40 (45%) of which
      had improved uptake in the immediate reinjection images. Only 9 of 135 (6%)
      segments with fixed defects on immediate reinjection imaging showed additional
      uptake with delayed reinjection imaging. These data suggest that imaging early
      after thallium reinjection is of value in the detection of reversible ischaemia
      after infarction, but that delayed reinjection imaging offers little additional
      benefit.

PMID- 7715892
TI  - Myocardial uptake of antimyosin antibody in idiopathic dilated cardiomyopathy and
      its relation to functional and morphological parameters.
AB  - Monoclonal 111In antimyosin (AMS) uptake indicates the presence of ongoing
      myocyte damage. In idiopathic dilated cardiomyopathy (IDC), there is diffuse
      myocyte damage. We have attempted to find a correlation between AMS uptake and
      functional myocardial parameters. With this purpose in mind, we studied two
      groups of subjects: group 1 comprised 19 subjects with IDC and group 2 comprised
      6 control subjects. In all subjects, an antimyosin scan was performed. Among the
      subjects with IDC, two-dimensional echocardiography was carried out to determine
      the left ventricular ejection fraction (LVEF) and left ventricular dimensions,
      and a gated blood pool study was undertaken to assess the LVEF at rest and end
      diastolic and end-systolic volumes. Three months later, repeat antimyosin
      scintigraphy and equilibrium gated blood pool were performed on 13 of the
      patients. The mean heart to lung (H/L) ratio in the IDC subjects was 1.82 +/-
      0.25 (range 1.42-2.25), a value significantly higher than that obtained in the
      controls: 1.41 +/- 0.12 (range 1.26-1.58) (P < 0.001). Linear regression analysis
      did not find a statistically significant correlation between H/L and gated blood
      pool or echocardiography measures. No marked changes in ejection fraction and
      antimyosin uptake were found between baseline and follow-up studies. Subjects
      with IDC have a high incidence of positive antimyosin scans, but antimyosin
      uptake is not related to any functional or morphological parameters.

PMID- 7715894
TI  - Diagnostic value of 99Tcm-d,l-HMPAO-labelled leukocyte scintigraphy in the
      detection of vascular graft infections.
AB  - Prosthetic vascular graft infection is a relatively uncommon complication of
      peripheral vascular surgery. We retrospectively analysed technetium-99m-d,l
      hexamethylpropylene amine oxime (99Tcm-d,l-HMPAO) labelled leukocyte scans of 21
      patients with a suspected vascular graft infection. Operative findings,
      bacteriological cultures, radiological findings or clinical follow-up were used
      to confirm the diagnosis. We found eight true-positive and six true-negative
      cases. There were no false-positive scintigraphic diagnoses. The false-negative
      rate was 33% (n = 7). Our results show a sensitivity of 53%, a specificity of
      100% and an accuracy of 66%. The conclusion is that a negative 99Tcm-d,l-HMPAO
      labelled leukocyte scan is of limited value in ruling out a vascular graft
      infection. A combination of computed tomography (CT-scan) and a 99Tcm-d,l-HMPAO
      labelled leukocyte scan is probably the most efficient way of diagnosing a
      vascular graft infection.

PMID- 7715895
TI  - A prospective study comparing SPET with MRI and CT as prognostic indicators
      following severe closed head injury.
AB  - Ten patients were studied prospectively afer severe closed head injury to
      determine the relationship between long-term clinical outcome and abnormalities
      detected by single photon emission tomography (99Tcm-HMPAO SPET), CT and MRI
      obtained within 60 days of injury. The ability of SPET to detect abnormalities
      not visualized by CT or MRI after cerebral trauma by the results of this study.
      Changes detected by SPET [global cerebral blood flow (gCBF) and number of
      regional cerebral blood flow (rCBF) deficits] soon after trauma were shown to be
      more closely correlated with long-term outcome than changes detected by MRI or
      CT. Templates were used to classify lesions by site and a multivariate analysis
      was undertaken to establish the importance of defect position in predicting
      clinical outcome. The results suggest that lesions in the temporal lobes, frontal
      lobes and basal ganglia are related to poor prognosis, and that SPET yields more
      useful prognostic data than the other methods.

PMID- 7715896
TI  - Inter-beat changes in left ventricular function with cardiomyoplasty as measured
      using MUGA scanning.
AB  - Dynamic cardiomyoplasty is a new surgical technique that uses electrically
      stimulated skeletal muscle to partially replace or reinforce the heart muscle in
      the treatment of advanced heart failure. Clinical experience with cardiomyoplasty
      is limited, which has precluded definitive conclusions about its value. We have
      studied the effect of cardiomyoplasty on the heart muscle when the skeletal
      muscle was being stimulated to coincide with alternate natural beats. The left
      ventricular function was assessed using radionuclide angiography during the beat
      immediately following skeletal muscle stimulation and during the beat immediately
      before stimulation. When the supported beat is compared with the unsupported
      beat, the results demonstrate that cardiomyoplasty improves the global and
      regional ejection fraction. The regurgitation index remains unchanged. The
      systolic peak emptying rate improves but the diastolic peak filling rate worsens.
      This latter finding provides additional information regarding the diastolic
      function of the heart following cardiomyoplasty, which is presently not well
      understood.

PMID- 7715897
TI  - Pretargetted imaging of colorectal cancer recurrences using an 111In-labelled
      bivalent hapten and a bispecific antibody conjugate.
AB  - In 11 patients recurrence of colorectal cancer was suspected by a rise in serum
      carcinoembryonic antigen (CEA) (nine cases), by a subocclusive clinical situation
      (one case) or by endoscopy (on an anastomosis, one case). Two-step tumour
      targetting was performed by a first injection of 0.1 mg kg-1 of unlabelled
      bispecific antibody conjugate (an anti-CEA Fab' fragment chemically coupled to an
      anti-diethylene triamine pentaacetate (DTPA)-indium fragment) followed 4 to 5
      days later by injection of the bivalent DTPA hapten labelled with 5 to 8 mCi
      111In. Planar scintigraphy, single photon emission computed tomographic (SPECT)
      360 degrees acquisitions and whole-body scans were obtained 4.5 and 24 h after
      injection of the radiolabelled hapten. Biodistribution was determined for eight
      patients at 48 h. The final diagnosis was confirmed histologically in nine
      patients (eight by second-look surgery, one by laparotomy). Overall, results were
      one true negative (1-year follow-up) and 10 true positive; however, for the three
      large liver metastases (3 to 6 cm), only the periphery of the metastasis had high
      uptake compared to normal liver. For pelvic recurrences, immunoscintigraphic (IS)
      contrast was better for small tumours. The highest tumour uptake was found for a
      1 cm diameter pelvic recurrence (7.2% i.d. kg-1). Mean tumour-to-blood ratios
      were 6.4. Thus, this two-step tumour targetting technique, which uses a
      bispecific antibody conjugate and an 111In-labelled bivalent hapten injected
      sequentially without chasing the excess bispecific antibody, provided
      satisfactory results in this preliminary clinical trial for detection of
      recurrent colorectal cancers.

PMID- 7715898
TI  - Planar, SPET and three-dimensional immunoscintigraphy of suspected recurrent
      colorectal cancer using 111In-B72.3 (Oncoscint CR-OV): effect of administered
      activity.
AB  - The monoclonal antibody conjugate 111In-B72.3 was the first such antibody-based
      radiopharmaceutical for tumour detection to be granted a propriety product
      licence in Europe. However, the optimum activity of 111In for planar and SPET
      imaging is yet to be established. A baseline study of 20 patients with suspected
      recurrent colorectal cancer has been carried out to assess any effect of
      administered activity of radionuclide on image quality and tumour detection. Ten
      patients were administered 80 MBq 111In-Oncoscint and 10 patients a larger amount
      of activity, 150 MBq (resulting in effective dose equivalents of 25 and 47 mSv,
      respectively). Planar, orthogonal SPET and 3D volume-rendered SPET images were
      obtained and the image quality was assessed. The clinical results were compared
      with computed tomography (CT) and in selected patients magnetic resonance imaging
      (MRI). No difference in the overall tumour detection was apparent between the two
      groups and the use of 150 MBq 111In for planar imaging alone cannot be justified.
      Orthogonal and 3D SPET imaging was helpful in confirming sites of uptake and may
      justify the use of the higher administered amount of activity; however, false
      positive results raise the need for caution in the interpretation of these
      images. Volume-rendered 3D images offer an attractive method of displaying
      antibody data and require further evaluation.

PMID- 7715899
TI  - The role of bone scintigraphy and other imaging modalities in knee pain.
AB  - The role of bone scintigraphy (planar and SPET) in the investigation of chronic
      knee pain is assessed in conjunction with other imaging modalities. A review of
      the literature has been undertaken and an imaging strategy suggested. It is
      concluded that bone scintigraphy has an important role to play as an imaging
      modality when investigating cases of chronic knee pain.

PMID- 7715900
TI  - Long-term cosmetic outcome and toxicity in patients treated with quadrantectomy
      and radiation therapy for early-stage breast cancer.
AB  - Breast conservation treatment followed, if useful, by adjuvant therapy is the
      treatment of choice in early breast cancer. Late cosmetic outcome and toxicity
      are important in comparing conservative treatment to mastectomy. We reviewed the
      records of 225 patients treated from 1981 to 1988 with a median follow-up of 74
      months (range 12-156 months). Cosmetic results, either reported by the physician
      (82.4%) or by the patients themselves (81.5%), were generally excellent or good,
      and tended to decline with time (69 and 75.5%, respectively). Toxicity was mild
      with arm edema (14.6%) being the most frequent symptom. No severe toxicities were
      observed. We conclude that overall cosmesis has been acceptable in this series
      and that a low rate of long-term toxicity can be expected with this conservative
      approach.

PMID- 7715901
TI  - Amplification of epidermal growth factor receptor gene and its relationship to
      survival in human gastric cancer.
AB  - The correlation between the clinical features in 103 patients with primary
      gastric carcinoma and amplification of epidermal growth factor receptor (EGFR)
      gene was analyzed retrospectively. EGFR gene amplification was examined by slot
      blot hybridization using DNA extracted from formalin-fixed, paraffin-embedded
      tissues. EGFR expression was also examined immunohistochemically using the same
      tissues with a monoclonal antibody that is monospecific for EGFR. In 5 of 103
      cases (4.9%), a 2- to 11-fold amplification of EGFR gene was detected. Four of
      these 5 cases were poorly differentiated adenocarcinomas. All of them had
      overexpressions of EGFR. The cumulative survival rate of patients with EGFR gene
      amplification was significantly lower than that of the patients without
      amplification (p < 0.05) and all of them died within 3 years. Except for tumor
      size (p < 0.03), there were no significant clinicopathologic differences between
      the two groups. On the other hand, 41 of 103 cases (39.8%) exhibited expression
      of EGFR. However, there was no significant correlation between EGFR expression
      and clinicopathologic factors or prognosis. These results indicate that EGFR gene
      amplification may occur in advanced stages during the progression and be an
      important indicator of poor short-term prognosis in gastric carcinoma.

PMID- 7715902
TI  - Relationships among the expression of epidermal growth factor receptor,
      proliferating cell nuclear antigen labeling index, and lymph node metastasis in
      gastric cancer.
AB  - The expression of epidermal growth factor receptor (EGFR), epidermal growth
      factor (EGF), transforming growth factor alpha (TGF alpha) and the labeling index
      of proliferating cell nuclear antigen (PCNA LI) were examined
      immunohistochemically in 288 gastric cancer patients, and the relationships
      between these results and the lymph node metastasis were studied. To investigate
      the relation between the expression of EGFR and PCNA LI, we divided the patients
      into the following three groups according to the immunohistochemical findings:
      group A, EGFR (+); group B, EGFR (-), and EGF(+) or TGF alpha(+); group C, EGFR(
      ), EGF(-) and TGF alpha(-). In the cancers invading submucosal or proper muscle
      layer, high-PCNA tumors (PCNA LI > or = 70) in both groups A and B had more
      frequent lymph node metastasis than in the intermediate-(40-69) and low- (< or =
      39) PCNA tumors. In the cancers invading subserosal layer or further, the
      frequency of metastasis in group A was over 78% and was not related to the PCNA
      range. In group B, metastasis was more frequent in high- and intermediate-PCNA
      tumors (about 80%) than in low-PCNA tumors (44%). These results suggest that
      growth regulation by EGFR is related to lymph node metastasis in gastric cancer,
      and the higher the PCNA LI of cancer cells becomes, the more frequent the
      occurrence of lymph node metastasis.

PMID- 7715903
TI  - Macrophage-like-cell-induced growth regulation of lymphoma cells.
AB  - Since hematopoietic stromal cells play a major role in regulating the growth and
      differentiation of hematopoietic cells, we have studied the effects of stromal
      cells on the in vitro growth of highly malignant murine RAW117-H10 lymphoma
      cells. These cells, when grown on a preformed layer of syngeneic Balb/c
      macrophage/monocyte cell line, J774A.1, stop proliferating 48 h after coculture.
      This stromal-cell-mediated growth regulation appears to require cell-to-cell
      contact between stromal cells and RAW117-H10 cells, since the J774A.1 cell
      supernatant did not significantly inhibit the in vitro growth of RAW117-H10
      cells. Because one of the cytokines produced by the macrophages is tumor necrosis
      factor (TNF)-alpha, which is known to inhibit certain tumor cells, we also
      studied the effects of various concentrations of TNF-alpha on the in vitro growth
      of RAW117-H10 lymphoma cells. TNF-alpha did not significantly affect the growth
      of these cells in vitro. However, TNF-alpha induced significant morphologic
      changes in these cells similar to those seen in plasma cytoid differentiation.
      Thus, our results indicate that the macrophage-like stromal cells regulate the in
      vitro growth of malignant lymphoma cells, and that direct cell surface contact
      between stromal and lymphoma cells is necessary for the growth regulation, and
      the growth inhibition is not due to TNF-alpha secreted by the macrophages. TNF
      alpha is associated with differentiation of these lymphoma cells.

PMID- 7715904
TI  - Ondansetron compared with granisetron in the prophylaxis of cyclophosphamide
      induced emesis in out-patients: a multicentre, double-blind, double-dummy,
      randomised, parallel-group study. Emesis Study Group for Ondansetron and
      Granisetron in Breast Cancer Patients.
AB  - This is the first double-blind clinical trial in a homogenous group of patients
      to compare the recommended dosing schedules of ondansetron and granisetron in the
      control of prolonged emesis after cyclophosphamide-containing chemotherapy (48%
      CMF, 35% EC) for breast cancer. A total of 514 patients were recruited. Of the
      488 patients included in the intent-to-treat analyses, 167 were randomised to
      group A [8 mg ondansetron intravenously (i.v.) + placebo by mouth (p.o.) before
      chemotherapy + 8 mg ondansetron p.o. twice daily (b.d.) until day 5], 155 to
      group B (placebo i,.v. + 8 mg ondansetron p.o. before chemotherapy + 8 mg
      ondansetron p.o. b.d. until day 5) and 166 to group C (3 mg granisetron i.v. +
      placebo p.o. before chemotherapy + placebo p.o. b.d. until day 5). On study day
      1, the groups were comparable with respect to the proportion of patients
      experiencing up to 2 emetic episodes (group A: 89%; B: 86%; C: 91%) and in the
      severity of nausea (no nausea; group A: 51%; B: 55%; C: 54%). Over the 5-day
      study period significantly more patients were rescued or withdrawn due to lack of
      response after the granisetron regimen (26%) than after the i.v. + p.o.
      ondansetron regimen (11%; p < 0.001). Since there was no difference in these
      parameters on day 1, this reflects differences on days 2-5 and was also reflected
      in the all-oral ondansetron group over this period (group B: 12%; C: 22% on days
      2-5). A significant difference in the severity of nausea after i.v. and p.o.
      ondansetron compared with granisetron was also observed over the 5-day study
      period (p = 0.009). This was reflected in a numerical difference in favour of the
      all-p.o. ondansetron regimen compared with the granisetron regimen (no nausea;
      group A: 33%; B: 34%; C: 25%). Again these differences reflected differences in
      nausea control on days 2-5, since no differences were observed on day 1. Logistic
      regression analyses adjusted for prognostic factors also revealed a significant
      difference (p = 0.011) in favour of the i.v. + ondansetron group compared with
      the granisetron group when complete plus major response was compared over days 2
      5. No significant differences in the safety profiles of the three treatment
      groups were observed. There were no severe or unexpected drug-related adverse
      events and as is well established for the serotonin receptor antagonists, mild
      constipation (mean 8%) and mild headache (mean 8%) were most commonly reported.

PMID- 7715905
TI  - Studies on clinicopathological features of lung cancer patients with K-ras/p53
      gene alterations: comparison between younger and older groups.
AB  - In order to define the roles of the K-ras and p53 genes in the development of
      lung cancer, especially in young adults, we compared the clinicopathological
      features of the patients between younger (< or = 45 years, n = 47) and older (<
      55 years, n = 50) groups. The gene alterations were examined by the polymerase
      chain reaction-single strand conformation polymorphism (PCR-SSCP) method. The K
      ras gene alterations were detected only in adenocarcinomas, and the p53 gene
      alterations in all histologic types of lung cancer. There were no significant
      differences in the frequency of both K-ras and p53 gene alterations between the
      younger and older groups (9 vs. 11%, 36 vs. 32%). In the younger group, but not
      in the older one, the percentage for smokers was significantly higher in the p53
      gene alteration-positive group than for the negative group (65 vs. 30%). As to
      the prognosis, there were no significant differences between the p53 gene
      alteration-positive and -negative cases in both the younger and older groups as
      well as in all subjects, while a tendency of poorer prognosis was observed in K
      ras gene alteration-positive cases than for the -negative ones with
      adenocarcinomas. These results suggest that (1) the K-ras and p53 gene
      alterations would have no special roles in terms of the lung carcinogenesis in
      young adults; (2) a positive relationship between smoking and p53 gene alteration
      would exist in young adults with lung cancer, and (3) K-ras gene alteration would
      become a prognostic factor in lung cancer.

PMID- 7715906
TI  - Nonseminomatous germ cell tumour of testis in Hong Kong Chinese patients.
AB  - Combination chemotherapy with multidisciplinary support results in excellent cure
      rate for nonseminomatous germ cell tumour of testis. 52 Chinese patients treated
      in two institutions in Hong Kong were reviewed retrospectively. 29 patients were
      stage I and IM and 3-year survival was 96% with a median follow-up of 49 months.
      23 patients were stage II and above and 3-year survival was 54% with a median
      follow-up of 21 months. The patient details are compared with a Western
      population, factors influencing outcome are discussed, and provision of optimal
      care outlined.

PMID- 7715907
TI  - Cathepsin D content in colorectal cancer. Correlation with cathepsin D activity
      and other biological parameters: a preliminary report.
AB  - Cathepsin D content and activity were determined in matched paired sets of
      colorectal tumor tissue and normal mucosa and correlated with a number of
      biological and clinical parameters. Significantly higher cathepsin D activity was
      measured in tumor cytosol compared to paired normal mucosa (p < 0.02), in Dukes'
      stage A tumors compared to Dukes' B and C (p < 0.05), in tumors < 5 cm compared
      to those > 5 cm, or in tumors with a low proliferation rate compared to those
      with a high proliferation rate (p < 0.05). Moreover, significant differences in
      enzyme activity between tumor tissue and paired normal mucosa were observed in
      node-positive and G2 tumors (p < 0.05). No significant correlation between
      cathepsin D activity and other biological parameters was found. Further, no
      differences in cathepsin D content between tumor tissue and paired normal mucosa
      were observed except in Dukes' stage A tumors (p < 0.02). A significantly
      increased cathepsin D content was also observed in tumors > 5 cm compared to
      tumors < 5 cm (p < 0.01). No relationship between tumor cathepsin D content and
      clinical stage was detected. However, a significant correlation (p < 0.05) was
      observed between the tumor-specific content of this enzyme and tumor grade.
      Finally, there was no relationship between tumor-specific cathepsin D activity
      and content (r = -0.27, p = 0.23). These data suggest that cathepsin D activity
      rather than content correlates with the malignant progression of colorectal
      cancer. This phenomenon should be taken into consideration when clinical studies
      are undertaken to assess the potential prognostic value of proteolytic enzymes
      involved in tumor progression.

PMID- 7715908
TI  - A randomized study of low-dose subcutaneous interleukin-2 plus melatonin versus
      supportive care alone in metastatic colorectal cancer patients progressing under
      5-fluorouracil and folates.
AB  - Chemotherapy with 5-fluorouracil (5-FU) and folates represents the first-line
      standard therapy for metastatic colorectal cancer, whereas at present there is no
      conventional second-time treatment. Because of its importance in generating an
      effective anticancer immune response, interleukin-2 (IL-2) could constitute a new
      promising therapy of advanced colon cancer. Generally, IL-2 may determine tumor
      regressions in colon cancer only when it is given at high toxic doses. Our
      preliminary studies have shown that the pineal hormone melatonin may amplify IL-2
      activity, which becomes active also at low doses in several tumor histotypes. On
      the basis, we have performed a clinical trial to evaluate the impact of low-dose
      IL-2 plus melatonin on the survival time in metastatic colon cancer, which
      progressed in response to 5-FU plus folates. The study included 50 metastatic
      colorectal cancer patients, who did not respond or progressed after initial
      response to first-line chemotherapy with 5-FU and folates. Patients were
      randomized to receive supportive care alone or low-dose subcutaneous IL-2 (3
      million IU/day for 6 days/week for 4 weeks) plus melatonin (40 mg/day orally). No
      spontaneous tumor regression occurred in patients receiving supportive care
      alone. A partial response was achieved in 3/25 patients treated with
      immunotherapy. Percent survival at 1 year was significantly higher in patients
      treated with immunotherapy than in those treated with supportive care alone (9/25
      vs. 3/25, p < 0.05). This study suggests that low-dose subcutaneous IL-2 plus
      melatonin may be effective as a second-line therapy to induce tumor regression
      and to prolong percent survival at 1 year in metastatic colorectal cancer
      patients progressing under 5-FU and folates.

PMID- 7715910
TI  - A phase II trial of cardioprotection with Cardioxane (ICRF-187) in patients with
      advanced breast cancer receiving 5-fluorouracil, doxorubicin and
      cyclophosphamide.
AB  - From January 1991 to August 1993, 237 women with metastatic breast cancer were
      recruited into a multicentric phase II clinical trial designed to assess the
      cardioprotective activity of Cardioxane (ICRF-187). All patients were treated
      with 5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2
      (FDC) and Cardioxane 1000 mg/m2, in cycles repeated every 3-4 weeks. Cardiac
      functions were assessed at baseline by physical examination, ECG, and resting
      ultrasound left ventricle ejection fraction (LVEF). The same tests were repeated
      regularly after the 3rd, 6th, 8th cycle and every additional 100 mg/m2 of
      doxorubicin. At the end of the study there were 212 evaluable patients. Prior to
      analysis, patients were stratified according to the presence of cardiac risks at
      study entry. One hundred thirty-three patients (63%) bore one or more cardiac
      risks. The average total cumulative dose of doxorubicin administered to the group
      was 311 mg/m2 (range: 200-900 mg/m2). Overall response (CR + PR) was 49.5%
      (105/212), with 12% of patients entering complete remission. General toxicity
      (WHO grading) was mild and tolerable; no excessive myelosuppression or related
      symptoms were observed. Three patients from the risk group experienced
      cardiotoxicity, with an LVEF fall below 45%, and had to be removed from the
      study. Another 3 patients (1 from the risk group) were removed from the study due
      to clinically documented congestive heart failure after 200, 300 and 400 mg/m2 of
      doxorubicin. In our study, Cardioxane (ICRF-187) did not influence the antitumor
      efficacy of FDC chemotherapy, nor did concomitant administration of Cardioxane
      and chemotherapy result in any other or severer toxicity than that already known
      for this regimen. Finally, the observation that 51% of patients with preexisting
      cardiac risks received doxorubicin at dose range of 450-900 mg/m2 without
      significant clinical or laboratory signs of cardiotoxicity supports the evidence
      that Cardioxane provided cardiac protection offering the possibility of longer
      doxorubicin chemotherapy.

PMID- 7715911
TI  - Permeability testing of glove materials for use with cancer chemotherapy drugs.
AB  - The present study evaluated the effectiveness of several types of hospital gloves
      that are recommended by the manufacturers for handling chemotherapy drugs. Gloves
      were examined for permeability against five cancer chemotherapy drugs
      (doxorubicin, cyclophosphamide, 5-fluorouracil, carmustine, and cisplatin) at
      several time points up to 2 h using a bacterial mutation assay as the measure of
      permeation. Of the 5 types of gloves tested at a single thickness, 4 were
      completely impermeable to all drugs and the remaining 1 demonstrated only limited
      permeability. A latex examination glove used for comparison was permeable to
      carmustine. One glove material that was tested as a double thickness was
      impermeable to the 5 drugs. Results indicate that various types of gloves may
      offer protection against exposure to chemotherapy drugs for healthcare workers.

PMID- 7715912
TI  - Systemic Hyperthermia Oncological Working Group. 1st annual meeting, New York,
      N.Y., USA. June 7-8, 1994.

PMID- 7715909
TI  - A phase II study of 72-hour continuous infusion consisting of cisplatin and 5
      fluorouracil for treatment of non-small cell lung cancer.
AB  - A combination chemotherapy consisting of a 72-hour continuous infusion of
      cisplatin (CDDP; 100 mg/m2/72 h) and 5-fluorouracil (5-FU; 3 g/m2/72 h) was
      conducted for inoperable non-small cell lung cancer (NSCLC). Sixty patients were
      accepted for this study between June 1988 and December 1990. Forty-seven patients
      were male (median age 68). Thirty-four patients had stage III and 26 had stage IV
      disease. The response rate was 25.0% (95% confidence interval, CI, 14.0-36.0%),
      median survival was 15.7 months. In squamous cell carcinoma, the response rate
      was 35.5% (95% CI, 18.7-52.3%) and median survival was 15.1 months. In non
      squamous cell carcinoma, the response rate was 13.8% (95% CI, 1.2-26.4%) and
      median survival was 17.7 months. There was a significant difference in response
      rate (p < 0.01), but no significant difference in survival (p = 0.36). Grade 3
      leukopenia was 11.7%, grade 3 and 4 thrombocytopenia was 13.3%. Grade 3 nausea
      and vomiting were 8.3%. One patient had grade 4 renal toxicity. However, there
      was no treatment-related death. This regimen was well tolerated. In multivariate
      analysis, the significant parameters were CEA, performance status and response.
      In conclusion, 72-hour continuous infusion of CDDP and 5-FU for treatment of
      NSCLC provides similar response and toxicity as previously reported regimens
      using CDDP.

PMID- 7715913
TI  - Morphometric analysis of exudative retinal arterial macroaneurysms: a geometrical
      approach to exudate curves.
AB  - We studied morphometrically the color transparencies and fluorescein angiograms
      of 5 patients with six exudative retinal arterial macroaneurysms. Our aim was to
      express the dependence of the exudate morphology upon the location of the
      macroaneurysm with an algebraic polynomial analysis. We derived the second-degree
      conical equations of the exudate curves and computed the location of their
      cardinal descriptive parameters. The relationship between the site of the
      macroaneurysms and the computed hypothetical parameters of their exudate curves
      revealed that the structural features of the exudates are dependent upon the
      distance of the macroaneurysm to the foveola, the gravitational force and the
      clearing capacity of the venous net. The point where the macroaneurysm develops
      approximately 3 mm from the center of the macula seems to be a 'crucial point'.
      Macroaneurysms located closer than this point may cause the exudates that occupy
      the fovea and create severe visual loss.

PMID- 7715914
TI  - Degradation of hyaluronate by the concerted action of ozone and sunlight.
AB  - The influence of ozone and sunlight in a concerted reaction on hyaluronate
      solutions was investigated. The kinematic viscosity of hyaluronate solutions is
      decreased by ozone-air mixtures and simultaneous radiation with sun rays within a
      few minutes, indicating a depolymerization of the hyaluronate molecule. The
      reaction is dependent on the concentration of ozone and on the time of exposure
      to ozone and sunlight. The concerted degradation of hyaluronate is more effective
      than the reaction with each component, ozone and sun rays, alone. We conclude
      that hyaluronate depolymerization by ozone and sunlight may be one factor for
      irritations of the eye by photochemical smog and increased exposure to sun rays.

PMID- 7715915
TI  - Nontoxic intravitreal dose of ofloxacin for rabbit retina.
AB  - We studied the nontoxic intravitreal concentration of ofloxacin, a new quinolone
      antibacterial agent, by evaluating its effects on in vitro and in vivo
      electroretinograms (ERGs) in albino and pigmented rabbits. After perfusion with a
      36 micrograms/ml solution of ofloxacin, the in vitro ERG remained unchanged. The
      in vivo ERG and the visually evoked potential remained unchanged 4 weeks after
      vitrectomy with 50 micrograms/ml ofloxacin, and the retina was within normal
      limits both ophthalmoscopically and histologically. Therefore, the retinal
      toxicity of ofloxacin is low and within safe limits at clinical dosage.

PMID- 7715916
TI  - Ocular drug safety and HMG-CoA-reductase inhibitors.
AB  - 150 patients suffering from primary hypercholesterolemia were divided into three
      different groups receiving (1) lovastatin, (2) simvastatin, or (3) fenofibrate as
      controls. The aim of the study was to detect possible drug-induced ocular side
      effects, especially in the lens. The study period was 2 years. Ophthalmological
      examination and Scheimpflug photography were performed at the beginning and every
      6 months. Increases or decreases in the visual acuity were distributed very
      similarly in the three groups. Definite evidence of side effects was not found,
      nor was there evidence of deleterious effects on refraction. The intraocular
      pressure revealed intraindividual fluctuations without clinical significance.
      Many changes were observed in the lens, all were minimal, including those of the
      extreme lens periphery which had no effect on visual acuity. The present study
      shows the great value of Scheimpflug photography with densitometric image
      analyses because of its objectivity when compared with other methods. Our
      observations provide good evidence that lovastatin and simvastatin have no
      undesirable toxic effects on the lens and other ocular tissues, compared with
      fenofibrate.

PMID- 7715917
TI  - Expression and secretion of transforming growth factor-beta in transformed and
      nontransformed retinal pigment epithelial cells.
AB  - The expression and secretion of different isoforms of transforming growth factor
      beta (TGF beta) were examined in cultured transformed and nontransformed human
      retinal pigment epithelial (RPE) cells. Transformed RPE cells were found to
      express high levels of TGF beta 1 mRNA, low levels of TGF beta 3 mRNA but no
      detectable TGF beta 2 mRNA. If the cells were grown under serum-free conditions
      the expression of TGF beta increased. The mRNA expression was accompanied by
      secretion of TGF beta 1 (but not TGF beta 2) protein into the culture media. By
      comparison, nontransformed RPE cells were found to secrete similar amounts of TGF
      beta as transformed cells but predominantly secreted TGF beta 2. The secretion of
      TGF beta from both transformed and nontransformed RPE cells increased if the
      cells were grown without serum. In conclusion, the results show that TGF beta is
      expressed and secreted by transformed and nontransformed human RPE cells and that
      this expression and secretion are regulated by the presence or absence of
      exogenous factors.

PMID- 7715918
TI  - Dose-response characteristics of galactose-induced cataract in the rat.
AB  - The onset and progression of cataract was investigated in weanling Sprague-Dawley
      rats fed 10, 15, 20 and 30% dietary galactose (groups 1-4) for 45-226 days.
      Cataracts were graded on a 0-5 scale. After 226 days, 9% of the rats fed 10%
      galactose developed lesions beyond the very early stage of cataractogenesis
      (grade 1). After 154 days 50% of the rats fed 15% galactose developed subcortical
      cataract (grade 3) with no nuclear cataract. In the rats fed 20% galactose, an
      initial rapid development by 31 days of a grade 3 cataract was observed in 50% of
      the eyes. Advancement to grade 4 and grade 5 cataract proceeded more slowly; by
      207 days, 45% of the eyes had grade 5 cataract. In rats fed 30% galactose, rapid
      vacuolization and development of nuclear cataracts (grade 5) were observed by day
      44. Dietary galactose at levels of 20 and 30% was associated with a significant
      reduction in weight gain at the early stage of dietary treatment. These
      observations demonstrate that 10-30% dietary galactose induces cataract in rat
      lens in a dose- and time-dependent fashion. These data serve to further establish
      this animal model as a useful model for studying the sequelae of
      cataractogenesis.

PMID- 7715919
TI  - Congenital nystagmus: fine structure of human extraocular muscles.
AB  - The ultrastructure of the extraocular muscles of patients affected by congenital
      nystagmus is still to be defined. Specimens obtained from patients suffering from
      either oculomotor congenital nystagmus or nystagmus associated with strabismus
      were studied and compared with specimens obtained from patients enucleated for
      various pathologies but not affected by any oculomotor system disorder. The
      scleral myotendinous junction and the muscle body (venter) were examined. In both
      these areas, damaged muscle fibers were found. 'Mitochondrial cores' and
      concentric myofibrils characterized the extraocular muscles of the patients with
      oculomotor congenital nystagmus. In the extraocular muscles of the patients
      affected by nystagmus associated with strabismus we also found mitochondria with
      concentric cristae surrounding a highly electron-dense spherical body and
      numerous, large rods. In conclusion, these data indicate that both contractile
      and mitochondrial modifications might be signs of an altered muscle function and
      seem to indicate that oculomotor congenital nystagmus should be included among
      the list of oculomotor myopathies.

PMID- 7715920
TI  - The influence of magnesium on visual field and peripheral vasospasm in glaucoma.
AB  - Previous studies indicated calcium channel blockers to be of some help for normal
      tension glaucoma patients. The present study evaluates the effect of magnesium, a
      'physiological calcium blocker', in 10 glaucoma patients (6 with primary open
      angle glaucoma, 4 with normal-tension glaucoma). All patients had a digital cold
      induced vasospasm. Magnesium (121.5 mg) was administered twice a day for a month.
      After 4 weeks of treatment, the visual fields tended to improve. All three video
      nailfold-capillaroscopic parameters [blood cell velocity (in mm/s) before and
      after cooling, cold-induced blood flow cessation (in seconds) as well as the
      number of capillaries per microscopic field which showed such a blood flow
      cessation] as well as digital temperature improved significantly. Systemic blood
      pressure and pulse rate remained stable. In conclusion, magnesium improves the
      peripheral circulation and seems to have a beneficial effect on the visual field
      in glaucoma patients with vasospasm.

PMID- 7715921
TI  - Conjunctival and corneal changes in chronic renal failure patients treated with
      maintenance hemodialysis.
AB  - Conjunctival and corneal depositions of calcium salts are common complications in
      hemodialysis (HD) patients. We examined 14 HD patients; in 11 (79%), typical
      conjunctival and corneal calcifications were found. Patients with calcifications
      were older than those without. Patients treated longer with HD were found to have
      a higher grade of calcifications. We did not find the highest grade of
      calcifications in our patients. Serum calcium, phosphate, product of calcium and
      phosphate and parathyroid hormone concentration did not differ in patients with
      or without calcifications.

PMID- 7715922
TI  - Effects on the corneal endothelium six months following photorefractive
      keratectomy.
AB  - Photorefractive keratectomy (PRK) with a 193-nm excimer laser has been shown not
      to destroy endothelial cells in vivo. However, this laser could damage
      endothelial cell metabolism, and result in damage over a longer term. In this
      paper, a comparison between the number and shape of corneal endothelial cells has
      been performed in 25 patients before and 6 months after PRK. These patients
      underwent treatment with myopic correction ranging from 2.5 to 17 dpt and with an
      estimated corneal thinning ranging from 25 to 170 microns. No significant changes
      in the number (p = 0.167) and shape (p = 0.075) of endothelial cells have been
      found. These results show that there are no long-term damages after PRK even in
      severely myopic eyes.

PMID- 7715923
TI  - The effect of some treatment variables on long-term results of argon laser
      trabeculoplasty.
AB  - Eighty-five eyes of 75 patients were retrospectively followed up for 5 years
      after argon laser trabeculoplasty. The effects of some treatment and patients
      variables on the results of trabeculoplasty were assessed. The laser power level
      or visible burn effect on the chamber angle did not have any statistically
      significant impact on the success rate or degree of intra-ocular pressure (IOP)
      decrease. A statistically significant level was reached by the degree of chamber
      angle pigmentation and the number of pre-operative antiglaucomatous medication.
      In eyes where trabeculoplasty was given as primary therapy, the IOP decrease was
      greatest.

PMID- 7715924
TI  - A new cornea-marking device for penetrating keratoplasty and refractive corneal
      procedures.
AB  - In penetrating keratoplasty, postoperative astigmatism is determined by a number
      of factors, including adaptation of wound edges, mode of trephination of both
      donor and patient cornea and, last but not least, suture techniques. We would
      like to introduce a new cornea-marking device for use in keratoplasty and
      epikeratophakia. This device helps the surgeon to center the trephine and to
      perform a perfect double running torque-antitorque suture. Additional single
      sutures are not necessary. A study of postoperative astigmatism following
      operations in which this device was used is under way.

PMID- 7715925
TI  - Canalicular reconstruction for difficult cases: lacrimal stents and multiple
      traction sutures.
AB  - Twelve cases with canalicular disorders were treated by a new technique using
      multiple traction sutures (MTS) under an operating microscope. The MTS using
      black silk or 5-0 nylon were applied at the medial canthus, near the upper and
      lower puncta and at the caruncle. Additional traction sutures were applied to
      locate a deep canalicular system if needed, resulting in a total of 5-10 traction
      sutures. The patient's face was turned sideways towards the left in the operation
      of the right eye, and to the right in the operation of the left eye. By using the
      new technique, the opening of the common canaliculus could easily be located
      without resorting to an open-sky technique requiring skin incision. A new
      canaliculus could easily be made using a free graft of oral mucous membrane
      between the common canaliculus and medial canthus with the help of MTS in 7 cases
      out of 12. As stents, a match-style silicone tubing, a nunachaku-style silicone
      tubing, an ordinary silicone tubing and a silicone tubing with a silicone sponge
      were used for 7, 1, 1 and 3 cases, respectively. After a mean follow-up 17.2
      months, symptomatic relief and patency of the lacrimal passage were achieved in
      all cases.

PMID- 7715926
TI  - Postpartum central retinal artery occlusion simulating Purtscher's retinopathy.
AB  - A 30-year-old woman noticed sudden visual loss in her right eye 3 days after a
      normal childbirth and without eclampsia during pregnancy. An ophthalmic
      examination revealed that she had impending central retinal artery occlusion and
      her right visual acuity was 20/2000, which recovered to 20/30. A systemic
      examination showed hypercoagulability and hyperlipidemia but no abnormal findings
      on brain CT scan and echocardiography. Clinical features of this case were very
      similar to Purtscher's retinopathy.

PMID- 7715927
TI  - Unilateral cytomegalovirus retinitis in a patient with immunoglobulin G2
      deficiency.
AB  - A benign course of cytomegalovirus (CMV) retinitis is reported in a young patient
      with selective immunoglobulin G2 (IgG2) deficiency, after corticosteroid
      treatment for inflammatory pulmonary disease. IgG2 deficiency is a specific
      disorder of humoral immunity and has little to do with defense against viruses.
      This case suggests that CMV retinitis can occur in patients with IgG2 deficiency,
      who have received steroids in a presumedly nonimmunosuppressive dose for
      associated respiratory disease.

PMID- 7715928
TI  - Proliferative vitreoretinopathy in Coats' disease. Clinicohistopathological case
      report.
AB  - We report the clinicohistopathological findings of the proliferative
      vitreoretinopathy in an eye with Coats' disease using the tissue obtained during
      surgery. A 28-year-old man, who had experienced poor vision in his right eye for
      a period of 4 years, was referred to our hospital. Examination revealed an
      extensive yellow exudate in the subretinal space and a tractional retinal
      detachment. Prominent teleangiectatic retinal vessels were also temporally
      present. Evident epiretinal membranes were present in the postequatorial area. We
      performed a scleral buckling, vitrectomy, membrane peeling, endophotocoagulation
      and silicone oil tamponade. A histological examination revealed that the
      epiretinal membrane consisted of collagen fibers, glial proliferation, foam cells
      and lymphocytes. The foam cell in the epiretinal membrane is a characteristic
      finding in an eye with Coats' disease.

PMID- 7715929
TI  - Ocular involvement in keratosis follicularis associated with retinitis
      pigmentosa. Clinicopathological case report.
AB  - In 1988, Itin et al. published the combination of keratosis follicularis (KF;
      Darier-White disease), an autosomal-dominantly transmitted genodermatosis, and
      retinitis pigmentosa (RP) in two brothers. One of these patients died
      unexpectedly at the age of 54 years. His eyelids and globes were histologically
      studied post mortem. Involvement of the eyelids has rarely been described
      clinically and not at all histologically. The skin and the intermarginal zone of
      the lids exhibited the typical changes of this cutaneous disease involving the
      follicles of the eyelashes. Focal keratinizations of the limbal conjunctiva, a
      regional increase in conjunctival goblet cells and a diffuse thickening of the
      basement membrane of the corneal epithelium were present. They are probably not
      specific for KF. The retinal findings were those of a typical late stage of RP.
      The combination of both genetically transmitted disorders could point to a damage
      in neighbouring gene loci. An abnormality of the metabolism of vitamin A was
      supposed to play a pathogenetic role in both diseases but remains speculative, as
      does a genetic linkage.

PMID- 7715930
TI  - New developments in visual acuity charts.

PMID- 7715931
TI  - Endogenous fluorescence of ocular malignant melanomas.
AB  - The endogenous fluorescence of human choroid, sclera, and retinal pigment
      epithelium (RPE) in normal tissue and tissue with uveal melanoma was studied in
      vitro by a non-invasive and non-destructive fluorescence technique which had
      previously been applied for the diagnostic evaluation of pigmented lesions of the
      skin. The fluorescence of the normal choroid is rather dark, the normal sclera
      exhibits blue fluorescence and the RPE bright yellow fluorescence due to deposits
      of lipofuscin. In choroidal melanoma, the lipofuscin granulae at the level of the
      retinal pigment epithelium are cleaved off above the tumour and broken up into
      small remnants. The fluorescence intensity emitted from the tumour is rather low
      which agrees with previous findings on skin melanomas. The results may become
      interesting for diagnostic evaluation of uveal melanomas, uveal naevi, and
      pigmented conjunctival tumours by endogenous fluorescence.

PMID- 7715932
TI  - [Setting up and organization of a rehabilitation center].

PMID- 7715934
TI  - [A special day for nursing: college-Krems].

PMID- 7715933
TI  - [Episodes of care in the rehabilitation of patients with head and brain
      injuries].

PMID- 7715936
TI  - The effects of perceived versus enacted social support on the discriminative cue
      function of spouses for pain behaviors.
AB  - This study examined the effects of spouse social support on patient displays of
      pain behaviors. A standardized behavioral observation method was used to record
      pain behaviors in 110 chronic pain patients while the spouse was present and
      while the spouse was absent. Patients and their spouses also completed paper and
      pencil measures of spouse-provided social support as well as a demographic
      questionnaire. Results indicated that pain behaviors varied as a function of
      spouse presence and the type, or dimension, of support considered. Patients
      reporting higher levels of enacted support displayed a greater number of pain
      behaviors irrespective of spouse presence, consistent with the operant theory.
      When a measure of perceived support was used, the pain behaviors displayed
      differed, depending upon the level of support and spouse presence. Results are
      consistent with support-seeking and cognitive-behavioral models of the effects of
      social support on outcome. We discuss our findings within the context of a
      multidimensional model of support and pain and we caution against strict
      application of the operant model in treatment programs. Additional research is
      warranted to better understand the impact of support on the rehabilitation of
      patients with chronic pain.

PMID- 7715935
TI  - Hypnosis and hierarchical pain control systems.

PMID- 7715938
TI  - Response of chronic neuropathic pain syndromes to ketamine: a role for
      norketamine?

PMID- 7715937
TI  - Rapid, reproducible pain relief with [131I]iodine-meta-iodobenzylguanidine in a
      boy with disseminated neuroblastoma.
AB  - [131I]Iodine-meta-iodobenzylguanidine ([131I]MIBG) is a radioactively labelled
      substance which is incorporated intracellularly by cells with neuroendocrine
      differentiation and used in the treatment of neuroendocrine malignancies. The
      agent was systemically administered on three occasions during a period of 16
      weeks to a 4-year-old boy afflicted with disseminated neuroblastoma and suffering
      from severe pain caused by the disease. Initially, during the weeks immediately
      prior to radionuclide therapy, the boy required continuous intravenous infusions
      of morphine. On the 3rd day after each treatment, morphine administration could
      be discontinued and the boy appeared to be pain free. His appetite returned to
      normal and he became more mobile. The therapy had a good effect on his pain on
      each of the three occasions. Recurrent side effects were thrombocytopenia and
      cystitis. It is concluded that treatment with systemic radiotherapy in the form
      of [131I]MIBG was easy to perform and effective in this case of disseminated
      neuroblastoma and illustrates that this primary therapy can be used for
      palliative purposes.

PMID- 7715939
TI  - The role of the basal ganglia in nociception and pain.
AB  - The involvement of the basal ganglia in motor functions has been well studied.
      Recent neurophysiological, clinical and behavioral experiments indicate that the
      basal ganglia also process non-noxious and noxious somatosensory information.
      However, the functional significance of somatosensory information processing
      within the basal ganglia is not well understood. This review explores the role of
      the striatum, globus pallidus and substantia nigra in nociceptive sensorimotor
      integration and suggests several roles of these basal ganglia structures in
      nociception and pain. Electrophysiological experiments have detailed the non
      nociceptive and nociceptive response properties of basal ganglia neurons. Most
      studies agree that some neurons within the basal ganglia encode stimulus
      intensity. However, these neurons do not appear to encode stimulus location since
      the receptive fields of these cells are large. Many basal ganglia neurons
      responsive to somatosensory stimulation are activated exclusively or
      differentially by noxious stimulation. Indirect techniques used to measure
      neuronal activity (i.e., positron emission tomography and 2-deoxyglucose methods)
      also indicate that the basal ganglia are activated differentially by noxious
      stimulation. Neuroanatomical experiments suggest several pathways by which
      nociceptive information may reach the basal ganglia. Neuroanatomical studies have
      also indicated that the basal ganglia are rich in many different neuroactive
      chemicals that may be involved in the modulation of nociceptive information.
      Microinjection of opiates, dopamine and gamma-aminobutyric acid (GABA) into the
      basal ganglia have varied effects on pain behavior. Administration of these
      neurochemicals into the basal ganglia affects supraspinal pain behaviors more
      consistently than spinal reflexive behaviors. The reduction of pain behavior
      following electrical stimulation of the substantia nigra and caudate nucleus
      provides additional evidence for a role of the basal ganglia in pain modulation.
      Some patients with basal ganglia disease (e.g., Parkinson's disease, Huntington's
      disease) have alterations in pain sensation in addition to motor abnormalities.
      Frequently, these patients have intermittent pain that is difficult to localize.
      Collectively, these data suggest that the basal ganglia may be involved in the
      (1) sensory-discriminative dimension of pain, (2) affective dimension of pain,
      (3) cognitive dimension of pain, (4) modulation of nociceptive information and
      (5) sensory gating of nociceptive information to higher motor areas. Further
      experiments that correlate neuronal discharge activity with stimulus intensity
      and escape behavior in operantly conditioned animals are necessary to fully
      understand how the basal ganglia are involved in nociceptive sensorimotor
      integration.

PMID- 7715941
TI  - Out-patient cognitive-behavioural therapy with amitriptyline for chronic non
      malignant pain: a comparative study with 6-month follow-up.
AB  - A study was carried out in a multidisciplinary pain clinic with the purpose of
      comparing the effectiveness of outpatient cognitive-behavioural therapy (CBT)
      with amitriptyline (AMI) to that of supportive therapy with AMI. The treatments
      were given weekly over 8 weeks. Global and continuous outcome measures were used.
      Analysis was by chi-square for global data and MANOVA with baseline scores as
      covariants for continuous variables. No significant differences could be
      demonstrated. The scores over a 6-month follow-up period suggested a delayed
      positive advantage for CBT but this only approached and did not achieve
      statistical significance. The findings are discussed.

PMID- 7715940
TI  - Hypnotic analgesia reduces R-III nociceptive reflex: further evidence concerning
      the multifactorial nature of hypnotic analgesia.
AB  - Mechanisms of hypnotic analgesia were investigated by examining changes in the R
      III, a nociceptive spinal reflex, during hypnotic reduction of pain sensation and
      unpleasantness. The R-III was measured in 15 healthy volunteers who gave VAS
      sensory and VAS-affective ratings of an electrical stimulus during conditions of
      resting wakefulness, suggestions for hypnotic analgesia, and attempted
      suppression of the reflex during non-hypnotic conditions. The H-reflex was also
      measured to monitor and control for general changes in alpha-motoneuron
      excitability. Hypnotic sensory analgesia was related to reduction in the R-III
      after controlling for changes in the H-reflex (R2 = 0.51, P < 0.003), suggesting
      that hypnotic sensory analgesia is at least in part mediated by descending
      antinociceptive mechanisms that exert control at spinal levels in response to
      hypnotic suggestion. The relationship between hypnotic affective analgesia and
      reduction in R-III approached significance (R2 = 0.26; P = 0.053). Reduction in R
      III was 67% as great and accounted for 51% of the variance in reduction of pain
      sensation. In turn, reduction in pain sensation was 75% as great and accounted
      for 77% of the variance in reduction of unpleasantness. The results suggest that
      3 general mechanisms may be involved in hypnotic analgesia. The first, implicated
      by reductions in R-III, is related to spinal cord antinociceptive mechanisms. The
      second, implicated by reductions in pain sensation over and beyond reductions in
      R-III, may be related to brain mechanisms that serve to prevent awareness of pain
      once nociception has reached higher centers, as suggested by Hilgard.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7715943
TI  - Pharmacological evidence for the involvement of the endogenous opioid system in
      the response to local inflammation in the rat paw.
AB  - We have investigated the role of the endogenous opioid system (EOS) on the
      inflammatory response induced by subplantar (s.p.) injection of saline (SS) and
      carrageenan (CA) in the hindpaw of the rat. The administration of intraperitoneal
      (i.p.) naloxone was used in order to unmask the effects of endogenous opiates
      released during peripheral inflammation. Three groups of rats received one of the
      following s.p. treatments: SS, CA, or no injection (NI). Pain pressure threshold
      (PPT), paw volume (edema) and local temperature were evaluated in baseline
      conditions and 3 h after treatment. In each group, the effects of i.p. vehicle,
      naloxone and (+)-naloxone (0.1 mg/kg) were also investigated. Both SS and CA
      induced a significant inflammatory response with hyperalgesia, edema and local
      hyperthermia. The i.p. administration of naloxone but not that of (+)-naloxone 15
      min prior to testing, significantly increased edema in all groups of treatment (P
      < 0.05), without altering PPT or local temperature. Two-way ANOVA revealed that
      treatment and drugs, as well as their interaction, had a significant impact on
      edema which was related to the effects of CA and naloxone. Our findings
      illustrate the involvement of the EOS in the physiological response to local
      injury, regulating microvascular leakage in the inflamed tissues.

PMID- 7715942
TI  - Differential effects of spinalization on discharge patterns and discharge rates
      of simultaneously recorded nociceptive and non-nociceptive spinal dorsal horn
      neurons.
AB  - Recordings were made simultaneously from 2-5 neurons at the same site in the
      lumbar spinal dorsal horn of pentobarbital-anesthetized rats. Neurons were
      classified as low-threshold (LT) or multireceptive (MR) according to their
      responses to non-noxious mechanical or noxious radiant heat stimuli of the skin.
      At the same recording sites neurons could be encountered which belong to
      different classes and/or which had mechanoreceptive fields which did not overlap.
      Cold blocks of the upper or lower thoracic cord or transsections of the upper
      cervical cord were made to evaluate the effects of spinalization on both the rate
      and pattern of background activity and/or noxious heat-evoked responses of
      different dorsal horn neurons under identical experimental conditions. At 24 of
      27 recording sites, spinalization had qualitatively or quantitatively different
      effects on the rate of background activity of simultaneously recorded neurons.
      Interspike interval (ISI) means of background activity were significantly reduced
      in 29 of 65 (44.6%) neurons, prolonged in 23 of 65 (35.4%) neurons, or unchanged
      in 13 of 65 (20%) neurons. MR neurons displayed a significantly higher incidence
      of decreased background activity 17 of 45 (37.8%) and a lower incidence of
      increased background activity (18 of 45, 40%) during spinalization than the LT
      neurons from which 1 of 12 (8.3%) decreased and 8 of 12 (66.6%) increased
      background activity. Almost all (95.4%) neurons changed their discharge patterns
      after spinalization. At 9 of 27 recording sites, the discharge patterns of
      simultaneously recorded neurons were affected differently by spinalization as
      revealed by the coefficient of dispersion of the interspike intervals (ISI),
      indicating changes in the tendency to discharge action potential in clusters
      (bursts). At the same recording sites the level of noxious heat-evoked responses
      of simultaneously recorded MR neurons was also differentially affected by
      spinalization. Nociceptive responses were significantly enhanced in 19 of 37
      (51.4%) neurons (137.8 +/- 142.6% of control, mean +/- SD), reduced in 13 of 37
      neurons (35.1%) (by 58.9 +/- 20.9%) and/or unchanged in 5 of 37 (13.5%) neurons.
      It is concluded that no general 'tone' of descending antinociception exists and
      that tonic descending excitatory and inhibitory systems may be active
      simultaneously modulating both the level and pattern of neuronal discharges.

PMID- 7715944
TI  - Development and validation of the Curtin Back Screening Questionnaire (CBSQ): a
      discriminative disability measure.
AB  - Disability accompanying occupational low back pain (LBP) can include a wide range
      of incapacitating symptoms which, for the practitioner, can be time-consuming and
      difficult to identify systematically. A questionnaire designed for case-finding
      and assessment could assist in both the early recognition of disability and in
      planning management. A suitable questionnaire for clinical use could not be found
      in the literature. The Curtin Back Screening Questionnaire (CBSQ) was developed,
      therefore, as a discriminative screening instrument to serve this purpose. The
      methods and results of the development and validation of the CBSQ are presented
      herein. Development of the questionnaire followed the principles of Kirschner and
      Guyatt (1985) employing data from 74 subjects with at least moderately severe
      work-related LBP. The research design for the validation was multiple-group
      repeated-measures with a study population of 150 subjects. The screening function
      of the questionnaire was developed through selecting 8 questions from the whole
      questionnaire using regression analysis. The questionnaire includes 79 items
      based on the subjects' perceived health status. The response structure of the
      CBSQ has been adapted from that of the General Health Questionnaire (GHQ) and
      some items in the CBSQ have been developed from items in the Sickness Impact
      Profile (SIP) and GHQ. The questionnaire discriminates effectively between
      subjects with different degrees of disability, it correlates quite well with the
      SIP, test-retest reliability for the whole questionnaire is 0.98, the receiver
      operating characteristics are more favourable than those for the SIP, and the
      CBSQ screening score provides an index of severity which correlates with work
      incapacity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715946
TI  - The formalin test: scoring properties of the first and second phases of the pain
      response in rats.
AB  - The formalin test is increasingly used as a model of injury-produced pain but
      there is no generally accepted method of pain rating. To examine the properties
      of various pain rating methods we established dose-response relations for
      formalin injected in the plantar surface of one hind paw, and the analgesic
      effects of morphine and amphetamine using the most frequently reported
      behavioural measures of pain (favouring, lifting, licking and flinching/shaking
      of the injured paw) and combinations of these. Licking, elevation and favouring
      of the injected paw showed a biphasic response at all formalin doses. Flinching
      varied in form across the time course of formalin, and the biphasic nature of the
      behaviour was not as apparent. In untreated rats all these behaviours were
      infrequent. Flinching and favouring were increased after injection of local
      anaesthetic into the paw but remained negligible relative to the effect of
      formalin. Grooming other than that directed to the injected paw was elevated in a
      dose-dependent manner by formalin. Intercorrelations between the behaviours were
      different for the initial response and the second phase. Correlational analysis
      indicated that no single behavioural measure was a strong predictor of formalin,
      morphine and amphetamine dose. A simple sum of time spent licking plus elevating
      the paw, or the weighted pain score of Dubuisson and Dennis (1977), were superior
      to any single measure (r ranging from 0.75 to 0.86). Addition of flinching and
      favouring to the combined pain score using multiple regression did not increase
      variance explained. Depending on the measure used, a sedative dose of
      pentobarbital produced apparent analgesia, hyperalgesia or no effect. The
      interphase depression of pain, as well as the analgesic effects of morphine and
      amphetamine, were all associated with increased motor activation. Power analysis
      indicated that using a moderate dose of formalin and a combined pain score gave
      the greatest power to detect differences in pain. It was also found that pain
      scores increase with ambient temperature and that rat strains may differ in
      formalin pain sensitivity.

PMID- 7715947
TI  - Regeneration in the central nervous system and related factors. Summary of the
      Bermuda Paraplegia Conference, April 1994 (International Spinal Research Trust).

PMID- 7715945
TI  - Effect of continuous intrathecal infusion of omega-conopeptides, N-type calcium
      channel blockers, on behavior and antinociception in the formalin and hot-plate
      tests in rats.
AB  - The effect of continuous intrathecal infusion of omega-conopeptides in the rat
      was examined to determine whether antinociception, as measured on the formalin
      and hot-plate (52.5 degrees C) tests, was altered and whether tolerance developed
      with chronic infusion of these agents. Infusion of 0.030 and 0.003 nmol/h SNX-111
      and 0.290 nmol/h SNX-239 was performed for either 2 days ('acute') or 7 days
      ('chronic') and was compared to the effect of 20 nmol/h morphine or saline. Both
      doses of SNX-111 and SNX-239 produced a significant reduction of the response to
      the hot-plate and formalin tests at both 2 and 7 days of infusion compared to
      saline infusion. In contrast, morphine only produced a significant effect on day
      2, but not on infusion day 7, indicating that tolerance had developed. The effect
      of SNX-111 was reversible, as shown by a return to nociceptive responses similar
      to saline-infused rats 2 days after the minipumps had been disconnected after a 7
      day infusion period. These data indicate that chronic infusion of omega
      conopeptides that block N-type voltage-sensitive calcium channels produce a
      powerful antinociception, with minimal development of tolerance.

PMID- 7715948
TI  - Anterior decompressive surgery for cervical ossified posterior longitudinal
      ligament causing myeloradiculopathy.
AB  - This paper reviews 88 patients (74 males and 14 females) who underwent anterior
      decompression and fusion for symptomatic ossified posterior longitudinal ligament
      of the cervical spine. Follow up averaged 8.5 years. Eighteen patients underwent
      one-vertebra, 59 two-vertebra, and 11 three-vertebra decompression with interbody
      fusion. The preoperative severity of symptoms significantly affected neurological
      recovery. Patients with three-vertebra spondylectomy showed significantly little
      neurological improvement. The return of patients to their previous activities as
      monitored at follow up was related to their preoperative neurological status. MRI
      findings appeared to be relevant to neurological recovery. Our findings suggest
      that anterior decompression is to be recommended for patients with less advanced
      preoperative symptoms and the involvement of one or two vertebrae.

PMID- 7715950
TI  - The functional limitations of tetraplegic hands for intermittent clean self
      catheterisation.
AB  - Since the introduction of intermittent self-catheterisation by Lapides et al, low
      pressure voiding methods have been adopted actively in our centre. A
      retrospective review of 47 patients with cervical spinal cord injury (CSCI) who
      performed independent (self) clean intermittent catheterisation (CIC) on
      discharge is presented. Their functional abilities were evaluated by both the
      Frankel and the Zancolli scales. Fourteen out of the 47 patients could manage
      independent CIC, 17 assisted CIC, nine tapped or voided voluntarily, two were
      discharged with a diaper, one with a suprapubic catheter, and four with an
      indwelling catheter. According to Frankel's classification, four patients were in
      A category, four in B, one in C and five in D among the group of complete CIC.
      C6A/C5B (right/left hand) by Zancolli's classification was the highest level of
      ability for all these 14 patients; and one patient (a 30-year-old male, Frankel B
      classification) could manage independent CIC with the aid of our special device.
      However, the practical limit of functional hands for independent CIC appeared to
      be about C6B1.

PMID- 7715949
TI  - Cervical laminoplasty in patients with ossification of the posterior longitudinal
      ligaments.
AB  - Cervical laminoplasty was the operation used for myeloradiculopathy secondary to
      ossification of the posterior longitudinal ligaments. Some 57 patients were
      followed up for 5-13 years (average: 7.8 years). The spinal canal from C3 to C7
      was surgically opened en bloc unilaterally with spacer bone grafting to maintain
      the laminae in a 'kept open' position and thus to implement posterior
      decompression. No serious major surgery-related complications were observed.
      Favourable results were obtained in 42 patients (74%), but those with advanced
      preoperative neurological symptoms did not improve. Patients with spinal canals
      seriously compromised by anterior ossified lesions recovered poorly. We concluded
      that laminoplasty is recommended for cervical myeloradiculopathy due to ossified
      posterior longitudinal ligaments for selected patients, but surgery should be
      done before the patient has developed serious neurological damage.

PMID- 7715951
TI  - Mutual influence between vesicourethral and anorectal function in spinal cord
      injury patients.
AB  - There is clinical evidence of a relationship between urethrovesical and anorectal
      dysfunction in spinal cord injured patients. This study was performed to assess
      how rectal distension could influence the results of urodynamic investigations.
      Ten patients with spinal cord injury were submitted to repeated urodynamic
      evaluations under different rectal conditions after performing complete anorectal
      testing. Distension of the rectal ampulla may interfere with vesicourethral
      function in spinal cord injured patients: in those with complete spinal cord
      lesions rectal distension causes a reduction in bladder compliance, earlier and
      higher amplitude of the first hyperreflexic contraction, and an increase in
      detrusor-external urethral sphincter dyssynergia. We suggest that urodynamic
      evaluation of spinal cord injured patients should not normally be performed if
      the patient has a full rectum.

PMID- 7715952
TI  - Intravesical atropine and suppression of detrusor hypercontractility in the
      neuropathic bladder. A preliminary study.
AB  - Twelve patients with detrusor hypercontractility secondary to spinal cord lesions
      were treated with intravesical atropine sulphate. Five patients expelled the
      solution almost immediately. In the seven patients who retained the solution the
      cystometric capacity increased by a mean of 301 ml (P < 0.01). The volume at
      which an unstable contraction occurred increased by a mean of 190 ml (P < 0.05)
      and the volume at which a urinary leak occurred increased by a mean of 297 ml (P
      < 0.05). The maximum hyperreflexic detrusor contraction pressure was reduced by a
      mean of 24 cm water (P < 0.05). No significant reduction in end fill pressure or
      compliance was observed though the increase in compliance approached
      significance. No side effects were observed and no differences were observed in
      pupillary reactions, blood pressure or pulse after the instillation of atropine.

PMID- 7715953
TI  - Obstructive effect of a closed 12F urethral catheter during the emptying phase of
      cystometry in patients with a spinal reflex bladder.
AB  - In spinal cord injured patients with a reflex urinary bladder urodynamic
      evaluation of the detrusor pressure during the emptying phase is important, but
      the methods are not yet standardised. The aim of this study was to examine
      whether the detrusor pressure is significantly affected by the presence of a
      catheter in the urethra. In seven patients with a spinal reflex bladder, the
      maximum detrusor pressure and the duration of detrusor contractions in cystometry
      with a suprapubic technique were compared with the corresponding measurements
      when a closed 12F catheter was added to mimic a transurethral cystometric
      technique. Four cystometries were performed with about 10 min intervals and the
      mean values from two cytometries without the urethral catheter were compared with
      the mean values from two cystometries with the catheter. After addition of the
      urethral catheter there was an increase of the mean maximum detrusor pressure
      form 8.4 to 10.5 kPa (P = 0.009). The mean duration of the detrusor contraction
      increased from 122 to 191 s (P = 0.031) and the mean time during which the
      detrusor pressure exceeded 4 kPa, in each contraction, increased from 60 to 150 s
      (P = 0.009). The average flow rate, calculated as the voided volume divided by
      the duration of a contraction, decreased from 1.4 to 0.6 ml s-1 (P =
      0.009).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715955
TI  - A medico-social survey of Romanians with spinal cord injury.
AB  - The problems faced by Romanian patients with spinal cord injuries when discharged
      home were investigated by a medico-social postal questionnaire. All 170 who were
      surveyed had been treated in the rehabilitation section of the Neurosurgical
      Clinic of Bucharest from 1.1.92 to 1.1.93 before being discharged home. Those who
      were still inpatients at the time of the survey were excluded. The response rate
      was high (133 patients (78%)). Fifty-four per cent were paraplegic and 44% were
      tetraplegic; 80% were men. They were facing serious financial difficulties
      through loss of their jobs and the absence of formal and efficient sources of
      social help. Urinary catheters, condom drainage and drugs were not easily
      available or were too expensive for many of the patients, and medical facilities
      were scarce in the remote villages. Sixty-six per cent (71% of whom were
      tetraplegic) spent most of their time in bed and very few had the resources to
      adapt their houses. It makes little sense to improve conditions in hospital if
      conditions at home are not also improved. This paper highlights some of the
      problems faced by such patients.

PMID- 7715954
TI  - A study of the factors affecting the outcome of vertebromedullary injuries.
AB  - Between 1982 and 1991, 194 patients were treated for cervical vertebromedullary
      injuries in the Department of Neurosurgery, Cerrahpasa Medical Faculty of the
      University of Istanbul. The data were evaluated with the multiple regression
      method using the SPSS/PC statistical package to predict the factors influencing
      the outcome. In the initial neurological examination, motor deficit was detected
      in 63.4% of the patients, sensorial deficit was seen in 53.6% of the patients and
      respiratory failure in 12.9%. Of these patients 46.4% were treated surgically and
      53.6% medically. Evaluating the findings and outcomes with the Frankel scale, no
      change in neurological status was detected in 44.8% of the patients. Improvement
      was detected in 36.1% and deterioration in 19.1%, the mortality rate being 18.6%.
      It is concluded that the main factor predicting the outcome of patients with
      vertebromedullary injury is the initial neurological status (P < 0.0001).

PMID- 7715956
TI  - The first 500 sacral anterior root stimulators: implant failures and their
      repair.

PMID- 7715957
TI  - Pathology of hyperextension injuries of the cervical spine, Paraplegia 1994; 32:
      367-374.

PMID- 7715958
TI  - Anyone for a game of bridge?

PMID- 7715960
TI  - Clinical disorders of water metabolism: hyponatremia and hypernatremia.

PMID- 7715959
TI  - The basics of fluid and electrolyte therapy.

PMID- 7715961
TI  - Disorders of potassium balance.

PMID- 7715962
TI  - Disorders of calcium, phosphorus, and magnesium.

PMID- 7715963
TI  - Renal tubular acidosis.

PMID- 7715965
TI  - The effects of humor on secretory immunoglobulin A levels in school-aged
      children.
AB  - Although research with adult subjects has demonstrated a positive correlation
      between humor and increased concentrations of secretory immunoglobulin A (S-IgA),
      the literature has not addressed whether humor might have a similar effect on
      children. Fifth grade student volunteers (N = 39) at an elementary school in
      Arkansas were randomly assigned to a treatment or control group. The study
      compared S-IgA levels collected before and after the treatment group subjects (n
      = 21) participated in a humor program and the control group subjects (n = 18)
      participated in an educational non-humorous presentation. Concentrations of
      immunoglobulin A were increased in fifth-graders who observed a humorous
      presentation, but remained unchanged in those who observed a non-humorous
      educational presentation. Further research is needed to determine the role that
      humor interventions might play in nursing's ongoing pursuit for health promotion
      and disease prevention in children.

PMID- 7715964
TI  - Iatrogenic immune suppression.
AB  - Tissue and organ transplants are now fairly common medical procedures encountered
      by pediatric nurses practicing in acute care settings. The understanding of what
      is known about the immune response to foreign antigens provides strong evidence
      of the immunologic barriers to organ and tissue transplantation. It is known that
      failure to suppress this immune response will result in degradation of
      transplanted organs and tissue. The extent to which these processes occur will
      depend on the action of T cells. Specific control of T cell action depends on the
      immunosuppressive agents administered. Administration of one or more of the
      identified iatrogenic immunosuppressive agents, at varied intervals and in varied
      doses, will surely affect the outcomes of the transplant process. Caring for
      children undergoing such a procedure requires an indepth knowledge of immune
      system function, as well as the various pharmacologic therapies employed.

PMID- 7715966
TI  - Immunosuppression in pediatric transplant patients.
AB  - Nurses in a variety of acute care settings are caring for children receiving
      transplants. Nurses caring for pediatric transplant patients need to understand
      the cellular components of the immune system; graft rejection and how it directs
      immunosuppressive therapy; and specific immunosuppressive agents with their
      appropriate application in the clinical setting. This knowledge provides a
      foundation for understanding aspects of nursing interventions as they relate to
      the pediatric transplant patient receiving immunosuppressive therapy.

PMID- 7715967
TI  - Shaken baby syndrome: a nursing perspective.
AB  - Child abuse by whiplash-shaking can lead to severe injury in infants, including
      cerebral damage, neurological defects, blindness, and mental retardation. These
      findings are seen often without external evidence of head injury. Nurses should
      suspect shaken baby syndrome (SBS) in infants less than 1 year of age who present
      with apnea, seizures, lethargy or drowsiness, bradycardia, respiratory
      difficulty, coma, or death. Subdural and retinal hemorrhages accompanied by the
      absence of external signs of trauma are hallmarks of the syndrome.

PMID- 7715969
TI  - Advanced practice nursing. Part 2--Opportunities and challenges for PNPs.
AB  - The recent movement towards defining advanced nursing practice offers
      opportunities and challenges for pediatric nurse practitioners and educators. The
      definitions of nurse practitioner, clinical nurse specialist, and advanced
      practice nurse indicate similarities and distinct differences in role definitions
      and expectations. Nurse practitioner practice and education will need to change
      significantly for nurse practitioners to be considered advanced practice nurses
      and to retain their legacy as nursing leaders.

PMID- 7715968
TI  - Advanced practice nursing. Part 1--Changes on the horizon: an interview with
      Doreen C. Harper.

PMID- 7715970
TI  - Advanced practice nursing. Part 3--commentary on confronting the challenges.

PMID- 7715971
TI  - Developmental approaches to examining young children.
AB  - The physical examination can be used to collect key clinical information, promote
      development, and educate children and parents about health and lifestyle choices.
      These results can be enhanced if the practitioner adapts his or her techniques to
      the child's developmental level.

PMID- 7715972
TI  - Cystic fibrosis and the pediatric caregiver: benefits and burdens of genetic
      technology.
AB  - Pediatric providers will be faced with questions about genetic disease more and
      more frequently as new technologies are developed for their diagnosis and
      treatment. With early genetic testing, improved treatments, and the potential for
      gene therapy, genetic diseases like cystic fibrosis, once thought to be fatal,
      are now considered chronic. Therefore, many such conditions will be seen not only
      in the PICU, but in ambulatory pediatric and adolescent settings. The life
      expectancy and psychosocial adjustment of children with chronic genetic diseases
      will depend not only on the severity of their disease but on the ongoing care and
      attention they receive. Because optimal care will require an awareness of the
      complex and variable moral and social issues raised at each stage of life,
      pediatric caregivers should be sensitized to issues in counseling families with
      genetic disease.

PMID- 7715973
TI  - Considerations for the use of a conceptual model in home health nursing.
AB  - The goal of home health nursing is to promote self-care capabilities in the
      client's home. A conceptual model for home health care would incorporate the
      nursing practice performed in the home on an intermittent skilled nursing visit.
      An appropriate model for home health care would include concepts of health
      service delivery, standards of care on which to focus practice, and guide the
      development of nursing interventions that are efficient and effective in our cost
      conscious society. The model would also include the ability to measure the
      quality of services delivered in the home.

PMID- 7715974
TI  - Transdermal fentanyl.

PMID- 7715975
TI  - What is your assessment? Turner syndrome.

PMID- 7715977
TI  - Contracts side by side.

PMID- 7715979
TI  - Effective transitions for families: life beyond the hospital.
AB  - The numbers of innovative inhospital programs for children are growing. Family
      focused activities can help families cope better with the hospital experience.
      Yet, to promote optimal healing, health care providers must recognize that a
      family's life goes on after the hospital stay. Many stresses make life difficult
      for families. Most families are resilient, but many can benefit from help in
      managing the transition from hospital to home. Valuing the small things children
      do, connecting with other families, locating community resources, understanding
      the short and long term needs of the child are some of the critical transitions
      for families.

PMID- 7715976
TI  - Patient education: effects of two teaching methods upon parental retention of
      infant feeding practices.
AB  - PURPOSE: The purpose of this study was to test a strategy for improving patient's
      retention of discharge teaching. METHODOLOGY: A pretest-posttest experimental
      design was used. Forty postpartum women were randomly assigned to a group. All
      subjects received infant feeding instruction until they reached criterion on the
      Infant Feeding Questionnaire. The experimental group received additional
      instruction on the same material (overlearning). The two groups were compared 2
      weeks later on the same questionnaire. Mean scores were compared by a t-test,
      demographic variables were correlated to outcomes, and effect of race or culture
      was analyzed by ANOVA. FINDINGS: The pretest showed no significant difference
      between the groups. Posttest scores were significantly higher for the
      experimental group. The mother's education was the only demographic variable that
      was correlated to the results. CONCLUSION: Mothers who receive overlearning
      beyond the mastery level retain significantly more of the material.

PMID- 7715978
TI  - Adolescent abortion and mandated parental involvement.
AB  - Laws mandating parental involvement in adolescent abortion decisions are in
      contrast to laws governing other aspects of adolescent health care. Studies
      support that adolescents are often capable of making mature, informed health care
      decisions. Nurses encountering these adolescents have a unique opportunity to
      support them through the system and enhance the decision-making process.

PMID- 7715980
TI  - What we can expect for health care in the Republican-dominated 104th Congress.

PMID- 7715981
TI  - Use of fluoroquinolones in pediatrics: consensus report of an International
      Society of Chemotherapy commission.

PMID- 7715982
TI  - Safety and immunogenicity of a cold-adapted influenza A (H1N1) reassortant virus
      vaccine administered to infants less than six months of age.
AB  - A safe and effective influenza vaccine is needed to prevent serious influenza
      illness in infants younger than 6 months of age. The purpose of this study was to
      determine whether two doses of the cold-adapted (ca) influenza A reassortant
      vaccine would be safe and immunogenic in this age group. In the first part of
      this study, infants received two doses of 10(5) or 10(6) 50% tissue culture
      infectious dose (TCID50) of the ca influenza vaccine separately from routine
      immunizations. In the second part of this study two 10(6) TCID50 doses of the ca
      influenza vaccine were given with routine immunizations at 2 and 4 or 2 and 6
      months of age. The ca influenza vaccine was well-tolerated by participants in
      both parts of this study. Two doses of the ca influenza vaccine were immunogenic
      in infants who received them separately from routine immunizations; 83% of
      vaccinees developed protective titers of serum hemagglutination-inhibition (HAI)
      antibody. In contrast, when the ca vaccine was administered with routine
      immunizations, protective HAI antibody titers were induced in only 20% of those
      immunized at 2 and 4 months of age and 50% of those immunized at 2 and 6 months
      of age. There were no statistically significant associations between HAI antibody
      response to ca influenza vaccination and dose schedule, presence of passively
      acquired maternal HAI antibody, ethnic group or breast-feeding status. Young age
      at the time of first immunization, however, appeared to correlate with decreased
      response to the hemagglutinin antigen of the influenza A virus.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7715984
TI  - Measles in Jordan: a prototype of the problems with measles in developing
      countries.
AB  - Until recently measles was a very severe illness of infancy and early childhood
      in Jordan. Incidence rates were estimated to be as high as 500 to 1000/100,000
      and case fatality rates were as high as 10%. Since 1981 mandatory and routine
      vaccination was introduced by the Ministry of Health. Because infants accounted
      for the most severe cases and almost all mortality, measles vaccine was given at
      9 months of age. No booster doses were recommended. Since 1981 there has been a
      steady shift in the age distribution of cases toward the older age group. In
      recent years children > 5 years of age accounted for > 60% of cases. Commensurate
      with that the mortality rate has decreased to almost nil in recent years. There
      is also evidence of a marked decrease of inpatient admission of measles cases to
      one of the largest hospitals, the Jordan University Hospital. Despite high
      immunization rates in excess of 88%, however, outbreaks of measles continue to
      occur. To evaluate the impact of measles vaccination on outbreaks, a study in one
      village in 1987 showed that there was almost no protective efficacy in children >
      5 years of age (relative risk 0.80 and confidence interval 0.06 to 0.67 vs.
      relative risk 0.73 and confidence interval 0.54 to 1.15). Although the current
      measles immunization strategy has decreased the mortality and morbidity rates, we
      propose that the continuing occurrence of outbreaks necessitates the addition of
      a booster dose after 15 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7715985
TI  - Hospitalizations for respiratory syncytial virus infection in Alaska Native
      children.
AB  - To characterize the epidemiology of Alaska Native children hospitalized for
      respiratory syncytial virus infections, we reviewed records of hospitalizations
      during the winter seasons of 1991 to 1992 and 1992 to 1993 at a hospital in
      Anchorage and a rural hospital in the Yukon Kuskokwim Delta (YKD) region of
      southwestern Alaska. The median age of hospitalization for respiratory syncytial
      virus infection was 2 months of age for YKD residents and 4.5 months for
      Anchorage residents. Sixteen percent of the hospitalized YKD children were less
      than 1 month of age, whereas the same was true for only 3% of the Anchorage
      children. Eight percent of the YKD patients required mechanical ventilation,
      whereas none of the Anchorage patients required ventilation. The median hospital
      stay was 4.8 days for YKD patients and 3.2 days for Anchorage patients.
      Hospitalization rates for infants less than 1 year of age were 33/1000 for Alaska
      Natives in Anchorage and 100/1000 for those in the YKD region. The extremely high
      hospitalization rate, especially among very young infants in the rural YKD
      region, points to a need for early preventive efforts.

PMID- 7715983
TI  - Measles vaccination of infants in a well-vaccinated population.
AB  - During outbreaks of measles, measles vaccine is recommended for infants
      considered to be at risk who are 6 months of age and older. In a prospective
      trial the serologic response to early measles immunization has been evaluated in
      125 infants given monovalent measles vaccine at 6 to 8.5 months of age and
      measles-mumps-rubella at 15 months. The response to vaccination was measured by
      plaque reduction neutralization (PRN) assay and enzyme immunoassay. Infants were
      grouped by the mother's immunization history: natural immunity (n = 60, Group 1);
      killed followed by live, further attenuated vaccine (n = 22, Group 2); and live,
      further attenuated vaccine only (n = 43, Group 3). The prevaccination geometric
      mean titer (GMT) by PRN for Group 1 (GMT = 69) was significantly higher than that
      of Group 2 (GMT = 18) or 3 (GMT = 13). Seroconversion (4-fold increase in PRN
      titer) rates after monovalent vaccine were 31, 71 and 76% for Groups 1, 2 and 3,
      respectively. Seroconversion percentages were higher when measured 6 to 8 weeks
      after vaccination compared with 4 to 5 weeks. After measles-mumps-rubella > or =
      97% of all infants had PRN titers > 120 and were measles IgG-positive by enzyme
      immunoassay. These data show that as demographics shift to a well-vaccinated
      maternal population and susceptibility in younger infants, measles vaccination
      before the currently recommended age will be effective.

PMID- 7715986
TI  - An epidemic of aplastic crisis caused by human parvovirus B19.
AB  - Human parvovirus B19 has been associated with several diseases. Aplastic crisis
      in patients with chronic hemolytic anemia, erythema infectiosum, hydrops fetalis
      and arthritis are among the common diseases caused by this virus infection. In
      the period between July, 1991, and March, 1992, 48 patients with aplastic crises
      were hospitalized at Saudi Aramco-Dhahran Health Center, Dhahran, Saudi Arabia.
      Forty-six patients had homozygous sickle cell disease, one had hemoglobin H
      disease and one had hereditary elliptocytosis. Evidence of recent human
      parvovirus infection was present in 91% of the cases. Leukopenia was present in
      21%, neutropenia in 27% and thrombocytopenia in 42%. This differs from previous
      reports in which red blood cell aplasia causing anemia was the only hematologic
      finding reported in most patients. There were no cases of erythema infectiosum in
      either the patients or the community during the epidemic and the reason for this
      phenomenon is not obvious. The almost limited occurrence of aplastic crisis in
      patients with sickle cell disease in a population with a high incidence of other
      types of chronic hemolytic anemias is of interest.

PMID- 7715987
TI  - Use of cytomegalovirus immunoglobulin in multiply transfused premature neonates.
AB  - We undertook a randomized, placebo-controlled, double blind trial of
      cytomegalovirus (CMV) immunoglobulin (CMVIG) for prevention of CMV-associated
      disease in 183 multiply transfused, premature neonates. CMVIG (150 mg/kg) or
      placebo was given within 24 hours of the first transfusion and at Day 10. If an
      intravenous catheter was still in place an additional dose was given between Days
      20 and 30. The globulin and placebo groups were well-matched with respect to
      birth weight, gestational age, Apgar score, birth to a CMV-seropositive mother,
      requirement for assisted ventilation and exposure to CMV-positive, unscreened
      blood products. Among infants followed for more than 10 days, 18 (10.5%)
      developed CMV infection; 9 had symptomatic CMV disease (5 placebo; 4 CMVIG).
      Among infants born to a CMV-seropositive mother, CMVIG use was associated with a
      CMV syndrome rate of 3.2% (95% confidence interval, 0.2 to 18.5%) compared to
      12.5% (95% confidence interval, 4.5 to 27.6%) among placebo recipients (P =
      0.163). Among placebo recipients infants born to CMV-seropositive mothers were
      more likely to have a virologically confirmed CMV syndrome than those born to a
      CMV-seronegative mother, despite receipt of blood not screened for CMV antibody
      (P = 0.012). Multivariate analysis demonstrated that two factors were
      independently associated with CMV acquisition: the volume of CMV-seropositive
      blood products transfused (P = 0.005); and birth to a CMV-seropositive mother (P
      = 0.006). Infusions of CMVIG were well-tolerated. This study reaffirms that
      perinatally acquired CMV disease is more common among infants born to CMV
      seropositive mothers than CMV-seronegative mothers, even without use of CMV
      screened blood products.

PMID- 7715988
TI  - Serial serum C-reactive protein to monitor recovery from acute hematogenous
      osteomyelitis in children.
AB  - Serial C-reactive protein (CRP) and erythrocyte sedimentation rate determinations
      were compared with clinical course and outcome at 1 to 2 months in 63 children
      with acute hematogenous osteomyelitis. High CRP values (163 +/- 108 mg/liter) on
      admission began to descend after the second day of treatment. From the fourth day
      on higher (P = 0.03 to P = 0.0001) CRP values distinguished a complicated from an
      uneventful course of acute hematogenous osteomyelitis and the patients
      symptomatic at follow-up (P = 0.003 to P = 0.0001) from asymptomatic ones.
      Children who developed extensive radiographic changes had elevated CRP values for
      a longer time (32 +/- 13 days) than children with typical changes (11 +/- 6 days,
      P = 0.0001). Erythrocyte sedimentation rates did not identify the type of
      clinical course but higher values on Days 4 to 7 distinguished children
      symptomatic at follow-up (P = 0.02) from asymptomatic ones. Monitoring serial CRP
      values can alert the physician to complications and predict outcome earlier than
      clinical signs or roentgenograms.

PMID- 7715989
TI  - Nosocomial transmission of tuberculosis infection in pediatrics wards.
AB  - Analysis of restriction fragment length polymorphisms is a well-established
      method of "DNA fingerprinting" that has been used to trace the transmission of
      particular strains of Mycobacterium tuberculosis during investigations of
      outbreaks. This report describe the use of restriction fragment length
      polymorphisms and arbitrarily primed polymerase chain reaction analysis to
      investigate two outbreaks of tuberculosis that affected six children who attended
      two pediatric wards in our hospital. In both outbreaks a history of household
      exposure to an adult with M. tuberculosis was obtained and suspected tuberculous
      contacts were identified. We have demonstrated unequivocally the strain
      relationship among the isolates in all the cases by restriction fragment length
      polymorphisms and arbitrarily primed polymerase chain reaction analysis. These
      techniques are very useful for performing epidemiologic studies of tuberculosis
      in children where natural history of tuberculosis infection is different from
      that in adults in that it is almost always primary infection rather than
      reactivation.

PMID- 7715990
TI  - Respiratory rate and signs in roentgenographically confirmed pneumonia among
      children in China.
AB  - A clinical study was conducted in three Chinese community hospitals to
      investigate the reliability of respiratory rate and various clinical signs in the
      diagnosis of pneumonia among 54 children less than 5 years of age.
      Anteroposterior chest film was used as the diagnostic standard. The cutoff
      criterion for rapid breathing was 50 breaths/minute for infants ages 2 to 11
      months and 40/minute in children 1 to 5 years old. Rapid breathing was a better
      predictor of pneumonia than rales (positive predictive values of 74.5 and 66.9%).
      Nasal flaring, chest indrawing, stridor and cyanosis of the tongue had predictive
      values of > 86%, but these clinical signs were observed in only a small
      proportion of patients. We recommend that village health workers use rapid
      breathing for diagnosis of pneumonia, rather than auscultation which is difficult
      and has proved unreliable. Sensitivity, specificity and positive and negative
      predictive values are presented for seven signs and symptoms of pneumonia.

PMID- 7715991
TI  - Pediatric lung abscess: clinical management and outcome.
AB  - Pulmonary abscess is an infrequent but significant problem in children. We
      retrospectively reviewed the charts of 45 children with documented lung abscesses
      admitted and treated at Texas Children's Hospital, Houston, over the 11-year
      period from January, 1982, to December, 1993, and report their presenting
      symptoms, bacteriology, clinical management and outcome.

PMID- 7715992
TI  - Acute pyelonephritis as a cause of hyponatremia/hyperkalemia in young infants
      with urinary tract malformations.
AB  - Obstructive uropathy causes tubular resistance to aldosterone and severe
      metabolic imbalance may be precipitated by an episode of pyelonephritis. In the
      last 3 years we investigated 52 episodes of pyelonephritis (positive urine
      culture, elevated C reactive protein, fever, elevated neutrophil count) in 50
      children between 15 days and 15 months of age. Ultrasonography voiding
      cystography and renal scintiscan were performed in all cases and i.v. urography
      in some. A salt-losing syndrome with hyponatremia and hyperkalemia (Na < 125
      meq/liter; K > 6.3 meq/liter) was observed in 17 infants < 3 months, accompanied
      by plasma aldosterone concentration of 5000 to 23,000 pg/ml (normal value, < 1000
      pg/ml). All these children had a severe urinary tract (UT) malformation
      (ureteropelvic junction stenosis in 7 cases, vesicoureteral reflux in 7,
      posterior urethral valves in 2, double system in 1). Thirteen infants < 3 months,
      7 with no urinary tract malformations, did not have electrolyte imbalance.
      Pyelonephritis was diagnosed in 20 other patients ages 4 to 15 months, including
      16 with severe UT malformations; 4 had normal UTs. We conclude that a salt-losing
      syndrome with tubular resistance to aldosterone can occur during pyelonephritis
      in young infants with congenital UT malformation, that the risk diminishes
      considerably or disappears after 3 months of age and that in the absence of UT
      malformation pyelonephritis does not cause acute sodium loss of clinical
      relevance.

PMID- 7715993
TI  - Transplacental transmission of hepatitis B virus: a familial case.

PMID- 7715994
TI  - Culture of Bordetella pertussis from three upper respiratory tract specimens.

PMID- 7715995
TI  - Responses to hepatitis B vaccine boosters in human immunodeficiency virus
      infected children.

PMID- 7715997
TI  - Nationwide surveillance of Kawasaki disease in Japan, 1984 to 1993.

PMID- 7715998
TI  - Once daily aminoglycoside dosing in full term neonates.

PMID- 7716001
TI  - Trimethoprim-sulfamethoxazole-associated central nervous system disease.

PMID- 7715999
TI  - Brain abscesses caused by Clostridium septicum as a complication of hemolytic
      uremic syndrome.

PMID- 7715996
TI  - Immune complex-dissociated p24 antigenemia in the diagnosis of human
      immunodeficiency virus infection in vertically infected Brazilian children.

PMID- 7716000
TI  - Acute hypertrophic cardiomyopathy possibly associated with Mycoplasma pneumoniae
      infection.

PMID- 7716002
TI  - Rectal prolapse in children associated with Clostridium difficile infection.

PMID- 7716003
TI  - Suppurative infections in children caused by non-beta-hemolytic members of the
      Streptococcus milleri group.

PMID- 7716004
TI  - Fever and neutropenia: defining low risk groups.

PMID- 7716005
TI  - Anxiety, insomnia and movement disorder in a fifteen-year-old hispanic female.

PMID- 7716008
TI  - XIVth Congress of the French Society of Hematology. Paris, France, February 3-4,
      1995. Abstracts.

PMID- 7716007
TI  - Diagnosis of tuberculosis in steroid recipients.

PMID- 7716006
TI  - Perinatal blastomycosis: the rest of the story.

PMID- 7716009
TI  - Professional development. First aid: assessment (continuing education credit).

PMID- 7716010
TI  - Divided state.

PMID- 7716011
TI  - A peaceful, public death.

PMID- 7716012
TI  - Threatening treatment.

PMID- 7716013
TI  - Pay campaign. The local picture.

PMID- 7716015
TI  - Complementary medicine. Verdict: not proven.

PMID- 7716016
TI  - Microbiological examination of urine in urinary tract infection.
AB  - Normally, urine in the bladder and the urinary tract from kidney to the last
      third of the urethra is sterile. When the urinary tract becomes infected with
      bacteria, an inflammation at the site of infection results in symptoms of urinary
      tract infection (UTI), and significant numbers of bacteria and white blood cells
      (WBC) appear in the urine. This paper describes how, by the examination of urine,
      the clinical microbiology laboratory contributes to the diagnosis, monitoring and
      treatment of UTI.

PMID- 7716014
TI  - Complementary medicine. The new fringe?

PMID- 7716017
TI  - Development of the link-nurse role in clinical settings.
AB  - The link-nurse scheme appears to be one way of narrowing the gap between theory
      and practice. This paper examines the concept, role, history and evolution of
      link nurses and, based on the author's personal experience of direct involvement
      in such a scheme, attempts to identify some of its advantages and drawbacks.

PMID- 7716018
TI  - Water vs conventional births: infection rates compared.
AB  - A comparative study of colonisation of infection rates in mother and baby was
      carried out. Thirty-two women were screened before delivery for the presence of
      micro-organisms. Half of this sample delivered in water and half did not. The
      birthing tub water was sampled before, during and after delivery. The most
      significant finding was that most women and babies showed no evidence of clinical
      infection. However, large numbers of Pseudomonas aeruginosa and Acinetobacter sp.
      were isolated from the water of one delivery; Pseudomonas aeruginosa was isolated
      initially from the ear and groin of the child and subsequently from multiple
      sites, including the umbilicus and 'septic skin lesions'. Lack of adherence to
      the cleaning protocol for water births appeared to be an important factor in this
      clinical episode.

PMID- 7716020
TI  - In the line of fire.

PMID- 7716019
TI  - Depression in life-threatening illness and its treatment.
AB  - Health-care professionals may feel at a loss when caring for the individual faced
      with a life-threatening illness who is also depressed, and may even consider that
      depression in such circumstances is inevitable. Assessment of the individual's
      mental state may be made difficult by physical symptoms and other factors,
      meaning that the individual does not always receive the necessary care. This
      paper hopes to show how simple, humanistic nursing interventions may help to
      improve the quality of life of such individuals.

PMID- 7716021
TI  - The ultimate sanction.

PMID- 7716023
TI  - Wound care. Healing practices.

PMID- 7716022
TI  - Wound care. Bullet wound fractures.

PMID- 7716024
TI  - Wound care. Recording risk factors.

PMID- 7716025
TI  - Wound care. A home from home.

PMID- 7716027
TI  - Wound care. Diagnosis of leg ulcers.

PMID- 7716026
TI  - Wound care. Compression therapy.

PMID- 7716029
TI  - Major to minor.

PMID- 7716030
TI  - Reaching out.

PMID- 7716028
TI  - Number of women using HIV services on the rise.

PMID- 7716032
TI  - Pay campaign. Striking precedents.

PMID- 7716031
TI  - Will to live. Interview by David Payne.

PMID- 7716033
TI  - The long shift.

PMID- 7716034
TI  - Help at hand.

PMID- 7716036
TI  - Adjustment to bereavement and loss in older people.
AB  - Nurses are now expected to be aware of grief and people's reactions to it. Nurse
      education emphasises the skills of recognising and supporting people as they
      experience the overwhelming emotions associated with death and dying. Some
      excellent books and articles have been written on the subject but it appears that
      only a small proportion of this material is directly applied to care of the
      elderly. Child death and other, more unusual circumstances of bereavement have
      lengthy literature bases but older people are particularly vulnerable to
      complicated grief reactions. Nurses need to be aware of these complications if
      older patients are to be cared for effectively as they adjust to the many losses
      in their lives. An understanding of the various processes and reactions involved
      will greatly enhance care of older people whenever they receive health care.

PMID- 7716037
TI  - Nurses' role in supporting people who are HIV positive.
AB  - This is the second of two papers which report the results of a research study of
      the psychological and emotional needs of people with HIV disease and how nurses
      might best offer support. This paper discusses the nurse's role in offering
      psychological and emotional support to patients. Inductive analysis of in-depth
      interviews with in-patients and their nurses revealed four aspects of the nursing
      role that were highly valued: nurses being caring; acting therapeutically;
      assessing and monitoring patients' changing needs for emotional support; and
      acting as educators.

PMID- 7716038
TI  - Nurse practitioners: the South Thames RHA experience.
AB  - Nurses are a key resource in primary and community care, but their effectiveness
      and efficiency is not easily evaluated. In this paper the authors describe a
      major project undertaken in England to demonstrate the outcomes of nursing
      practised at an advanced level. The key lessons learnt from this study are
      explained, together with some pointers for the way forward for nurse
      practitioners in primary care.

PMID- 7716035
TI  - Capital investment: how purchasers and providers are making the move.

PMID- 7716040
TI  - Qualitative nursing research: the issues and pitfalls.
AB  - This paper discusses socio-cultural problems that nurses may encounter when
      undertaking participant observation in nursing situations. Being aware of
      problems and evolving strategies to deal with them before starting studies may
      better equip nurses to resolve such difficulties.

PMID- 7716039
TI  - New ideas on fractionation and accelerated radiotherapy.
AB  - Radiotherapy given with a view to cure has traditionally been given daily Monday
      to Friday over a period of six to seven weeks. This paper discusses the
      implications of giving radiotherapy in an accelerated form (CHART) and the
      implications.

PMID- 7716041
TI  - Multidisciplinary bedside notes: an experiment in care.
AB  - An experimental system of multidisciplinary medical records was introduced in an
      elderly ward at St George's Hospital, London. The new-style notes improved
      multidisciplinary communication in goal-setting and care-planning and, by placing
      the record at the foot of the patient's bed, brought the focus of patient care to
      the patient's bedside. Major difficulties included duplication of paperwork,
      refiling after discharge and the matter of confidentiality. All the members of
      the multidisciplinary team were in favour of continuing the system, however, and
      recommended its use in other wards.

PMID- 7716042
TI  - Klinefelter's syndrome.

PMID- 7716043
TI  - Working abroad. Mean state of health.

PMID- 7716044
TI  - High anxiety.

PMID- 7716045
TI  - Mix and match.

PMID- 7716046
TI  - Performance-related care.

PMID- 7716048
TI  - [Pancreatic ascites].

PMID- 7716047
TI  - Infusion therapy: principles and practice.

PMID- 7716049
TI  - [Pulmonary hemodynamics in obstructive sleep apnea or overlap syndrome].
AB  - We studied pulmonary haemodynamics at rest and on exercise in 44 consecutive
      patients with moderate to severe obstructive sleep apnea (OSA), mean AHI > 40.
      The diagnosis was confirmed by standard polysomnography (PSG). According to
      history and results of spirometric measurements patients were divided to two
      groups, pure OSA and OSA complicating chronic obstructive pulmonary disease
      (overlap syndrome). In 34 pts with OSA (31 M, 3 F), means: age 45 +/- 8 years,
      body weight 108 +/- 22 kg, BMI49, VC 107 +/- 16% of N, FEV1 101 +/- 15% of N,
      PaO2 71 +/- 10 mmHg, PaCO2 39 +/- 3 mmHg, PSG showed AHI 66 +/- 15. Pulmonary
      haemodynamics at rest were within normal limits: PPA 16 +/- 5 mmHg, PW 7 +/- 3
      mmHg, CO 4.5 +/- 1.5 l/min, PVR 184 +/- 92 dyne.s.cm-5. On low grade exercise (40
      W) PPA increased to 31 +/- 10 mmHg, Pw to 12 +/- 6 mmHg and CO to 8.6 +/- 4.0
      l/min, PVR remained unchanged. In eight pts abnormal rise in PPA on exercise
      resulted from the increase in driving pressure (PPA-Pw). In 2 pts it was due to
      abnormal increase in wedge pressure. In ten male pts presenting with COPD means:
      age 53 +/- 8 y, body weight 109 +/- 11 kg, BMI49, VC 53 +/- 14% of N, FEV1 36 +/-
      16% of N, PaO2 57 +/- 10 mmHg, PaCO2 47 +/- 7 mmHg, PSG showed AHI 63 +/- 20. All
      pts presented with pulmonary hypertension (PH) at rest, PPA ranging from 21 to 37
      mmHg, mean 26 +/- 5 mmHg. We conclude that patients with OSA have normal PPA at
      rest, 1/2 of them have PH on exercise due to restriction of pulmonary arterial
      bed and/or left ventricle dysfunction. Pts with overlap syndrome have moderate
      resting PH resulting from alveolar hypoxia.

PMID- 7716050
TI  - [Releasing activity of superoxide radicals by neutrophils and monocytes in
      hemodialyzed patients with chronic renal insufficiency].
AB  - Superoxide anion (O2-.) production by neutrophils and monocytes was measured in
      the peripheral blood of 23 patients hemodialyzed for 14 years. The O2-.
      production by these cells decreased as the time of hemodialysis advanced. The
      correlation between O2-. production and peripheral blood smears was also
      evaluated. Patients with higher neutrophils percentages had lower O2-. production
      by neutrophils and monocytes. These results indicate that an abnormally increased
      counts of neutrophils and monocytes in peripheral blood of hemodialyzed patients
      may depress immunoregulatory function. In addition, decreased O2-. production by
      these cells should be considered when assessing the defence mechanism and
      susceptibility to infection of these patients.

PMID- 7716051
TI  - [Change of platelet function after the beginning of repeated hemodialysis
      treatment in patients with uremia].
AB  - The disturbances of platelet function in end-stage renal failure varies in
      dialysed and non-dialysed patients. We examined some platelet function in 11
      uremic patients treated conservatively (TC) and, again in the same patients, 3
      month after the beginning of repeated hemodialysis treatment (HD). The blood
      samples were taken before hemodialysis. In TC patients normal platelet count,
      prolonged bleeding time, normal platelet aggregation, unchanged PF4 activity and
      decreased PF3 availability were shown, compared with control group. In HD
      patients also normal platelet count and prolonged bleeding time were noted, but
      increased platelet aggregation, increased PF4 activity and PF3 availability were
      observed, compared with control group and with TC patients. We conclude that in
      TC patients rather decreased platelet function was observed; after the beginning
      of hemodialysis treatment some platelet function became significantly enhanced,
      which suggests platelet activation. Moreover, in HD patients the disturbances of
      platelet function before dialysis were shown, then it is possible that platelet
      activation persists in interdialytic period.

PMID- 7716054
TI  - [Gastro-esophageal reflux disease (Part I). Etiopathogenesis, clinical symptoms].

PMID- 7716052
TI  - [Direction of pharmacotherapeutic changes used in cardiovascular diseases
      assessed by examination of two population samples from Warsaw].
AB  - The aim of the study was to analyse the changes in pharmacotherapy of ischaemic
      heart disease (HD) and arterial hypertension (AH) between 1984 and 1988 using the
      results of screenings of two independent samples of Warsaw inhabitants. In this
      period the prevalence of IHD in Warsaw population aged 35-64 increased by 4.3%
      (from 30.3% to 31.6%) as well as the percentage of treated subjects by 19.5%
      (from 39.0% to 46.6%). Prevalence of arterial hypertension (AH) decreased in this
      period by 4.7% (from 35.8% to 34.1%) whereas the percentage of undertaking
      pharmacotherapy in these patients increased by 47.9% (from 33.8% to 50.0%) as
      well as the effectiveness of undertaken treatment (goal of treatment: < or =
      160/95 mmHg) increased by 115.8% (from 22.8% to 49.2%). In subjects with IHD
      selected from general population the consumption of nitrates, beta blockers and
      calcium channel blockers increased and these drugs were the most frequently taken
      in IHD. In treatment of AH diuretics, the most frequently used in 1984, were
      replaced, to some extent, in 1988 by beta blockers and calcium channel blockers.
      Consumption of drugs by general population, expressed in DDD/1000 i/day, changed
      too--the consumption of beta blockers increased in 1988 twice, of calcium channel
      blockers 3-fold and of nitrates 1.5 fold, whereas that of dipyridamole decreased
      by 60%, while comparing of these consumption in 1984.

PMID- 7716055
TI  - [Gastroesophageal reflux (Part II). Diagnosis, clinical complications,
      treatment].

PMID- 7716053
TI  - [Human recombinant interferon gamma in the treatment of atopic dermatitis].
AB  - Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by
      various immunologic abnormalities. We have studied the efficacy of recombinant
      human interferon gamma (rhINF-gamma) administered subcutaneously at a dose of
      0.05 mg/m2 in ten patients with severe AD. Patients were treated for 4 weeks.
      They have shown marked clinical improvement starting from the third week of
      treatment. The efficacy of the drug varied, with erythema, dryness and
      lichenification being the most responsive symptoms. There was no change in serum
      immunoglobulin E and IgG4 levels. Whole blood eosinophil count decreased only
      transiently and was accompanied by a tendency to lower values of serum eosinophil
      cationic protein. Patient with AD showed an increased expression of a T-cell
      surface activation marker CD 25 as compared to healthy controls. Moreover,
      clinical improvement was roughly paralleled by the decrease in this T-cell
      activation marker. We conclude that rhINF-gamma is a novel efficacious
      therapeutic approach in severe AD. We suggest that its primary action might be
      related to the inhibition of T-cell activation.

PMID- 7716056
TI  - [A case of kidney stone with unusual frequency of renal colic--possible influence
      of environment on lithogenesis].
AB  - In the present paper we described a 36 years old female, who expelled
      approximately 2000 stones from the urinary tract during the last 18 years.
      According to the clinical and laboratory tests the lithogenic factors such as
      abnormalities of calcium, phosphate, oxalate, magnesium and purine metabolism
      were excluded. The cystinuria and other forms of tubular nephropathies did not
      exist. Taking into account two following facts: 1) no evidence of renal calculi
      when the patient was outside her own house and 2) very high concentration of
      calcium in her home tap water, the role of environmental factors in the
      pathogenesis of nephrolithiasis in presented patient is very likely.

PMID- 7716057
TI  - [Coexistence of severe aortic insufficiency and systemic lupus erythematosis with
      antiphospholipid syndrome--case report].
AB  - We presented the coexistence of the severe aortic insufficiency and the systemic
      lupus erythematosus with antiphospholipid syndrome in 33-years old woman. She was
      qualified for the operation of the prosthesis aortic valve replacement after she
      was treated with steroids. During the operation, the heart infarct of the
      inferior wall had been observed, but finally in the postoperation period the
      heart efficiency improvement was observed. We have discussed same theories and
      clinical experiences of lupus erythematosus with antiphospholipid syndrome and
      clinical sequels.

PMID- 7716058
TI  - [Cardiovascular complications after renal transplantation].

PMID- 7716059
TI  - [Professor Jan Roguski--life and achievements of the honorary member fo the
      Polish Society of Internal Medicine].

PMID- 7716061
TI  - Characterization of binding sites for neuropeptide FF on T lymphocytes of the
      Jurkat cell line.
AB  - Neuropeptide FF (NPFF) is a neuropeptide with antiopiate properties able to
      antagonize the action of both endogenous and exogenous opiates. Because we have
      recently shown that NPFF modulates the proliferation of human T lymphocytes, we
      have searched for binding sites for this peptide on T lymphocytes. Our study
      shows that T lymphocytes of the Jurkat cell line express binding sites for
      [125I]YLFQPQRFamide, an iodinated analogue of NPFF. This binding is time and dose
      dependent, reversible, saturable, and may be resolved in two distinct components
      of high and low affinity. The opiate receptor agonists mu, delta, and kappa, as
      well the antagonist naloxone, were unable to affect binding. Beside the effects
      of opiates on immune cells, our results suggest that an antiopiate peptide, such
      as NPFF, could play a role in the modulation of the immune system.

PMID- 7716060
TI  - Somatostatin antibody does not influence bombesin-induced inhibition of gastric
      acid secretion in rats.
AB  - The influence of peripheral somatostatin immunoneutralization on intravenous
      (i.v.) and intracerebroventricular (ICV) bombesin-induced inhibition of gastric
      acid secretion (GAS) was investigated with the somatostatin monoclonal antibody,
      CURE.S6, in rats. The somatostatin antibody, injected i.v. in conscious rats with
      a chronic gastric fistula and i.v. catheter, did not modify basal GAS, whereas in
      urethane-anesthetized rats the basal GAS was increased by 150%. In conscious
      rats, somatostatin (15 micrograms/kg/h, i.v.) inhibited basal GAS by 50% after
      injection of control antibody but not after pretreatment with the somatostatin
      antibody. With pretreatment with a control antibody, bombesin (10
      micrograms/kg/h, i.v.) inhibited basal GAS by 60% in conscious rats and by 50%
      the acid response to pentagastrin infusion in urethane-anesthetized rats.
      Bombesin injected ICV (3 and 10 ng/10 microliters/rat) inhibited basal GAS by 50%
      and 70%, respectively, in conscious rats pretreated with a control antibody. The
      somatostatin antibody injected i.v. before i.v. or ICV injection of bombesin did
      not influence bombesin-induced inhibition of GAS in conscious or anesthetized
      rats. These results show that peripheral somatostatin does not play a major role
      in the inhibition of gastric acid secretion induced either by ICV or i.v.
      administration of bombesin or basal acid secretion in conscious rats.

PMID- 7716062
TI  - Structure-function studies of motilin analogues.
AB  - Over 100 motilin fragments and analogues, including monosubstituted C-terminal
      deleted analogues, conformationally restricted analogues, analogues with peptide
      bond isoteres (CH2-NH), and N-terminal fragments adjunct to an amphiphilic helix,
      were synthesized by solid-phase methodology, purified by reverse-phase HPLC, and
      assayed in vitro in a muscle strip bioassay (rabbit duodenum) and in a
      radioligand binding assay on crude membrane extracts from smooth muscle (rabbit
      antrum). The data suggest the existence of three distinct regions involved in the
      interaction of motilin with its receptor: the N-terminal region (amino acids 1-7)
      constitutes the minimal basic unit of binding and activity; the transition region
      (amino acidsa 8-9) links the N-terminal and C-terminal regions; and the C
      terminal region (amino acids 10-22) forms an alpha-helix that stabilizes the
      interaction of the N-terminal residues at the active site.

PMID- 7716063
TI  - Ontogeny of IGF-1 and the classical islet hormones in the turbot, Scophthalmus
      maximus.
AB  - The ontogeny of the endocrine pancreas of a teleost, the turbot (Scophthalmus
      maximus), was investigated by the use of double immunofluorescence. Clustered
      insulin (INS)-immunoreactive (IR) cells were observed on the first day after
      hatching. During the following days, the islet largely increased in size and some
      smaller islets appeared. All islets consisted only of INS-IR cells. Between day 5
      (onset of exogenous feeding) and 7, somatostatin (SOM) and glucagon (GLUC) cells
      appeared. In the large (principal) islet, the SOM-IR cells intermingled with the
      INS-IR cells. In the secondary islets, they occurred at the periphery. The GLUC
      IR cells were located at the periphery in all islets. Subsequently, two-four
      additional small principal islets appeared. At day 11, pancreatic polypeptide
      (PP)-IR cells were present in principal islets and secondary islets. Starting
      with day 11, in all islets, insulin-like growth factor 1 (IGF-1) immunoreactivity
      was localized in numerous PP-IR cells and GLUC-IR and some SOM-IR cells. It also
      occurred in enteroendocrine cells that seemed to contain none of the classical
      islet hormones. The early appearance of INS correlates with its key role in the
      regulation of fish protein and lipid metabolism. Islet-derived IGF-1 might
      inhibit the regulation of INS secretion in a paracrine manner and may be highly
      involved in growth-promoting processes.

PMID- 7716064
TI  - Central C-type natriuretic peptide augments the hormone response to hemorrhage in
      conscious sheep.
AB  - The effect of intracerebroventricular infusions of C-type natriuretic peptide
      (CNP-22, 5 micrograms/h for 3 h) or vehicle on the neurohumoral response of
      conscious sheep (n = 7) to acute moderate hemorrhage (15 ml/kg in 15 min
      performed 1 h after start of CNP) was studied. CNP alone (prehemorrhage) induced
      a transient rise (after 30 min) in heart rate (p = 0.0005), plasma aldosterone (p
      = 0.007), ACTH (p = 0.049), and cortisol (p = 0.049), with values returning to
      control levels immediately prehemorrhage. Hemorrhage caused arterial pressure to
      fall (15 mmHg) and heart rate to rise similarly on both study days. Compared with
      vehicle, posthemorrhage responses of AVP (p = 0.05) and cortisol (p = 0.004) were
      greater during CNP. Thus, central CNP-22 augmented the hypothalamic-pituitary
      adrenal axis at baseline and in response to hemorrhage in conscious sheep.

PMID- 7716065
TI  - alpha-MSH changes cyclic AMP levels in rat brain slices by an interaction with
      the D1 dopamine receptor.
AB  - The exposure of rat brain slices containing caudate putamen and accumbens nuclei
      to alpha-MSH or dopamine (DA) results in an increase in cyclic AMP (cAMP) levels.
      When tissues are compared with those containing both alpha-MSH and DA, a
      reduction in the cyclic nucleotide is observable. This study was carried out to
      determine whether variations in tissular cAMP levels induced by alpha-MSH might
      be explained by an interaction between the peptide and some dopaminergic
      receptors. Therefore, we measured cAMP in tissues and medium in response to alpha
      MSH in the presence of haloperidol, the selective D1 (SCH 23390) or D2
      (sulpiride) antagonists, or the selective D1 (SKF 38393) or D2 (bromocriptine)
      agonists. Haloperidol by itself induced no changes either in the cAMP content or
      in the cAMP efflux to the medium. When slices were exposed to alpha-MSH and
      haloperidol, the latter blocked the alpha-MSH effect of inducing an increase in
      the content of cAMP. None of the specific antagonists (at the administered doses)
      induced changes in the content of cAMP when compared with the control group. The
      presence of SCH 23390 in the incubation medium together with alpha-MSH yielded a
      reduction in cAMP levels compared with those incubated with alpha-MSH. A slight
      stimulatory effect on cAMP formation was observed when the dopaminergic agonists
      (SKF 38393 10 microM) were used. We conclude that alpha-MSH interacts with the D1
      dopamine receptor, changing the cAMP levels in striatum and accumbens nuclei.

PMID- 7716066
TI  - Characterization of endothelinA receptors in cerebral and peripheral arteries of
      the rat.
AB  - We have characterized and quantified endothelin receptors in rat brain (anterior
      cerebral) and peripheral (aorta, carotid, and caudal) arteries, with the use of
      [125I]endothelin and quantitative autoradiography. Endothelin binding was
      saturable, of high affinity, and totally displaced by the selective endothelin
      ETA antagonist BQ 123. A single class of ETA receptors is located in the medial
      layer of peripheral and cerebral arteries, and its quantification by
      autoradiography allows study of their regulation and function.

PMID- 7716069
TI  - Role of hydrophobic and hydrophilic forces in peptide-protein interaction: new
      advances.
AB  - A considerable part of important biological processes is governed by the
      noncovalent association of peptides and proteins. Various types of intermolecular
      forces may be involved in the formation of these molecular assemblies. This
      review gives a brief account of the physicochemical bases of interactive forces,
      with special emphasis on their impact on various peptide-protein interactions;
      summarizes the newest biochemical and biophysical methods for the study of such
      interactions; and discusses the role of various hydrophilic and hydrophobic
      forces in peptide-protein interactions in various fields of life sciences, such
      as immunology, enzymology, receptor binding, and toxicology.

PMID- 7716068
TI  - Bioactive cyclic dipeptides.
AB  - Cyclic dipeptides are among the simplest peptide derivatives commonly found in
      nature. Most cyclic dipeptides found to date appear to have emerged as by
      products of fermentation and food processing. However, many are endogenous to
      members of animal and plant kingdoms; these include cyclo(Pro-Leu), cyclo(Pro
      Val), cyclo(Pro-Phe), cyclo(Ala-Leu), cyclo(Pro-Tyr), cyclo(Pro-Trp), and
      cyclo(His-Pro). Although the five cyclic dipeptides--cyclo(His-Pro), cyclo(Leu
      Gly), cyclo(Tyr-Arg), cyclo(Asp-Pro), and cyclo(Pro-Phe)--exhibit interesting
      physiological and/or pharmacological activities in mammals, only one of these,
      cyclo(His-Pro), has been conclusively shown to be endogenous to mammals. On the
      other hand, cyclo(Leu-Gly), cyclo(Tyr-Arg), and cyclo(Asp-Pro) are structurally
      related to endogenous peptides Pro-Leu-Gly-NH2 (melanocyte-stimulating hormone
      release inhibiting factor), Tyr-Arg (kyotorphin), and Val-Pro-Asp-Pro-Arg
      (enterostatin), respectively, which may serve as precursor peptides. It needs to
      be determined, however, whether these peptides can indeed result from the
      processing of their respective precursors. In conclusion, it appears that cyclic
      dipeptides are a relatively unexplored class of bioactive peptides that may hold
      great promise for the future.

PMID- 7716067
TI  - Effects of administration of oxytocin in association with gonadotropin-releasing
      hormone on luteinizing hormone levels in rats in vivo.
AB  - Gonadotropin-releasing hormone (GnRH) and oxytocin both stimulate the secretion
      of luteinizing hormone (LH), although with different characteristics. Therefore,
      interaction between oxytocin and GnRH in the control of LH may be postulated. We
      developed models for investigating whether oxytocin can modulate GnRH action on
      LH in vivo. Pentobarbitone is known to pharmacologically isolate the pituitary
      from hypothalamic GnRH. We found that after pentobarbitone anesthesia of female
      rats at proestrus, oxytocin caused a synergistically enhanced LH response to
      administered GnRH (p < 0.04). In a second series of experiments, female
      proestrous rats were anesthetized with althesin. This anesthetic allows transport
      of endogenous GnRH from the hypothalamus to the pituitary. In control animals,
      which received no exogenous hormone, there was a surge in the mean LH
      concentration on the evening of proestrus, indicating the presence of endogenous
      GnRH activity. Thus, the novel model enables detection of interactions of
      administered hormones with endogenous GnRH. Administration of GnRH plus oxytocin
      in the afternoon of proestrus caused a reduction (p < 0.01) in the mean level of
      LH observed in the evening. The reduction was larger than if GnRH alone was
      administered. Following althesin anesthesia, rats sometimes had low LH levels on
      the afternoon of proestrus. There was a statistically significant difference
      between the number of rats that received oxytocin plus GnRH and had low LH levels
      and the number with low LH levels in the control group (p < 0.02). Neither of the
      hormones administered alone had a significant effect. Thus, it appears that
      oxytocin accentuated the effect of GnRH in reducing LH concentrations in althesin
      anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716070
TI  - Kidney angiotensin II receptors and converting enzyme in neonatal and adult
      Wistar-Kyoto and spontaneously hypertensive rats.
AB  - The aim of the present study was to correlate the development of the renin
      angiotensin system (RAS) in the kidney of the rat with the development of genetic
      hypertension. Immature (1-week-old) and adult (12-week-old) normotensive Wistar
      Kyoto (WKY) and spontaneously hypertensive kidney rats (SHR) were used for
      quantification of angiotensin II (ANG II) receptors and angiotensin converting
      enzyme (ACE) binding sites using quantitative autoradiography. In both neonatal
      and adult animals of either strain, ANG II receptors were of AT1 subtype. In all
      kidney areas of 1-week-old rats. ANG II receptor density was higher in SHR than
      WKY. Binding density increased with age in WKY rats; thus, in the glomeruli and
      the outer stripe of the outer medulla of 12-week-old WKY, binding was
      significantly higher than that present in age-matched SHR. [125I]351A binding to
      ACE was highest in the outer medulla and not detectable in glomeruli. In 1-week
      old rats, binding to ACE was higher in WKY than in SHR strain. No differences in
      ACE binding were found between adult SHR and WKY rats, with the exception of the
      inner stripe of the outer medulla, where no binding was detected in SHR. Our
      results support the hypothesis that the RAS in kidney is developmentally
      regulated and is involved in the development and maintenance of genetic
      hypertension in SHR.

PMID- 7716071
TI  - Effect of angiotensin II on the proliferation of mammotrophs from the adult rat
      anterior pituitary in culture.
AB  - We measured the influence of prolactin-releasing neuropeptides on mammotroph
      proliferation in cultures of rat adenohypophysis cells using flow cytometry.
      Angiotensin II (AII) increased mammotroph proliferation. Other peptides with
      hormone-releasing activities did not promote growth. Tamoxifen inhibited
      mammotroph proliferation in control and AII-containing cultures and the
      inhibition was reversed with beta-estradiol. Saralasin, an AII receptor
      antagonist, suppressed not only AII-induced mammotroph proliferation but also
      luteinizing hormone-releasing hormone (LHRH)-induced proliferation. These results
      suggest that hypothalamic LHRH stimulates AII release from gonadotrophs and that
      AII, with estrogen, controls mammotroph proliferation in rat pituitary.

PMID- 7716072
TI  - Bombesin-induced changes of sensory transmission in the dorsal column nuclei.
AB  - Bombesin was intracisternally administered to determine the effects on the
      neuronal activities of the dorsal column nuclei (DCN) of anesthetized rats.
      Although averaged afferent somatosensory transmission through 22 DCN neurons did
      not appear to be altered by bombesin (-1.11 +/- 3.5%), 12 of them were actually
      augmented (+17.15 +/- 2.7%) and 10 of them were suppressed (-26.15 +/- 4.9%)
      during 40 min after bombesin (0.01 microgram) administration. Pretreatment of a
      bombesin antagonist ([Leu13,Psi(CH2NH)Leu14]bombesin, 0.1 microgram) blocked the
      effects of bombesin. Lower dose (0.001 microgram) of bombesin did not exert any
      influences. These results suggest that bombesin may heterogeneously influence
      afferent somatosensory information in the brain stem of the rat.

PMID- 7716075
TI  - Periviscerokinin (Pea-PVK): a novel myotropic neuropeptide from the
      perisympathetic organs of the American cockroach.
AB  - A myotropic neuropeptide was isolated from extracts of 1000 abdominal
      perisympathetic organs of males of the cockroach, Periplaneta americana. This
      peptide, termed periviscerokinin, has excitatory actions on the hyperneural
      muscle of Periplaneta americana. After peptide sequence analysis and mass
      spectrometry, the structure of this peptide was confirmed by chemical synthesis
      and bioassay to be Gly-Ala-Ser-Gly-Leu-Ile-Pro-Val-Met-Arg-Asn-NH2. This sequence
      is different from the other known myotropic peptides in insects. The threshold
      concentration for stimulatory effects of the synthetic peptide on the isolated
      hyperneural muscle was about 10(-9) M, suggesting a physiological role as a
      neurohormone.

PMID- 7716074
TI  - PACAP stimulates glucose output from the perfused rat liver.
AB  - The effects of PACAP on hepatic glucose metabolism were examined using the flow
      through perfusion method for fed rat livers, because some of the glucagon
      superfamily peptides stimulate hepatic glucose output. Glucose output was
      significantly stimulated in a dose-dependent manner by more than 1 nM PACAP-27.
      The potency of its stimulation was equal to that of PACAP-38, greater than that
      of VIP, and clearly lower than that of glucagon. The cAMP output was also
      increased significantly by more than 1 nM PACAP-27; however, the degree and
      profile of cAMP output were not in parallel with those of glucose. Theophylline
      did not affect these stimulatory effects. On the other hand, in the perfusion
      experiment with Ca2+ free perfusate, the degrees of increase in glucose output
      induced by 15 and 40 nM PACAP-27 were significantly reduced. In conclusion, PACAP
      stimulates glucose output from the perfused rat liver, and Ca2+ rather than cAMP
      plays an important role in this action as a second messenger.

PMID- 7716073
TI  - Differential effects of the nonpeptide neurotensin antagonist, SR 48692, on the
      pharmacological effects of neurotensin agonists.
AB  - In in vitro studies, SR 48692, a nonpeptide neurotensin receptor antagonist,
      inhibited the binding of [3H] or [125I]neurotensin to membrane preparations from
      10-day-old mouse brains and from HT-29 cells with Ki values of 3.9 and 8.6 nM,
      respectively. SR 48692 also antagonized the neurotensin-induced mobilization of
      intracellular calcium in HT-29 cells, in agreement with previous findings. In rat
      cerebellar slices SR 48692 blocked the increase in cyclic GMP levels evoked by
      neurotensin in a dose-dependent manner. In vivo, SR 48692 antagonized the
      increase in rat brain mesolimbic dopamine turnover induced by the systemically
      active neurotensin peptide, EI [(N-Me)Arg-Lys-Pro-Trp-tert-Leu-Leu]. No effects
      on dopamine turnover of either EI or SR 48692 were observed in the striatum. SR
      48692 did not antagonize the EI-induced decreases in mouse body temperature and
      spontaneous locomotor activity (LMA) or the decreases in LMA induced by ICV
      administered neurotensin. Although other explanations are possible, these
      findings support the hypothesis that a subtype of the NT receptor may mediate the
      locomotor and hypothermic actions of this peptide and that it is different from
      the NT receptor that is involved in dopamine turnover.

PMID- 7716076
TI  - Occurrence of analogues of the myotropic neuropeptide orcokinin in the shore
      crab, Carcinus maenas: evidence for a novel neuropeptide family.
AB  - By use of an enzyme immunoassay that was developed for the determination of
      orcokinin, a myotropic neuropeptide of the sequence NFDEIDRSGFGFN from the
      crayfish, Orconectes limosus, immunoreactive material was detected in extracts of
      thoracic ganglia from the shore crab, Carcinus maenas. Isolation of the
      immunoreactive material was achieved by the following steps: 1) prepurification
      by gel filtration, 2) immunoaffinity chromatography on an anti-orcokinin IgG
      protein-A sepharose column, and 3) reversed-phase HPLC. The HPLC profile after
      affinity purification revealed three main immunoreactive peptides that were
      rechromatographed. None of these peptides was identical to orcokinin in terms of
      retention time. Automated gas-phase sequencing revealed these peptides to be
      analogues of orcokinin differing in one amino acid residue. They were named
      [Ser9]-, [Ala13]- and [Val13]orcokinin (NFDEIDRSSFGFN, Mr 1549.3; NFDEIDRSGFGFA,
      Mr 1475.3; NFDEIDRSGFGFV, Mr 1503.9). Carboxypeptidase A treatment of the
      peptides indicated a free C-terminus. Complete characterization of the three
      peptides was achieved from approximately 230 thoracic ganglia of Carcinus maenas.

PMID- 7716077
TI  - Blockade of endogenous GRF at dark onset selectively suppresses protein intake.
AB  - This study examined whether endogenous central GRF activity contributes to the
      increase in macronutrient intake shown by rats at dark onset. Animals were
      habituated to two diets: carbohydrate-fat and protein-fat. Antiserum raised
      against GRF (aGRF; 1% and 10% solutions) was microinjected into the
      suprachiasmatic nucleus/medial preoptic area (SCN/MPOA) at dark onset, and
      macronutrient intake was determined at 1, 2, and 4 h postinjection. aGRF blocked
      the increase in protein intake normally seen at dark onset, but had no effect on
      carbohydrate intake. These findings suggest that endogenous GRF activity in the
      SCN/MPOA region of the brain contributes to the circadian and nutritional
      organization of food intake.

PMID- 7716080
TI  - Cellular colocalization of diuretic peptides in locusts: a potent control
      mechanism.
AB  - Locust abdominal ganglia are shown to colocalize Locusta-diuretic peptide-,
      leucokinin I-, and lysine vasopressin-like immunoreactivity in posterior lateral
      neurosecretory cells. Extracts of abdominal ganglia were partially purified by RP
      HPLC then dot immunoassay screened with the same antisera used for
      immunocytochemistry. Locusta-diuretic peptide-like immunoreactive material
      coeluted with synthetic Locusta-diuretic peptide, and leucokinin-like
      immunoreactive material coeluted with locustakinin. Lysine vasopressin-like
      material eluted in fractions that also showed Locusta-diuretic peptide and
      leucokinin I immunoreactivity. The diuretic activity of synthetic Locusta
      diuretic peptide and locustakinin is demonstrated, and they are shown to act at
      least additively to promote Malpighian tubule fluid secretion. The immunoreactive
      neurosecretory cells are assumed to express at least these two peptides, and a
      model for promoting fluid secretion is proposed.

PMID- 7716079
TI  - Isolation and preliminary biological characterization of KPNFIRFamide, a novel
      FMRFamide-related peptide from the free-living nematode, Panagrellus redivivus.
AB  - A novel FMRFamide-related heptapeptide, Lys-Pro-Asn-Phe-Ile-Arg-Phe-NH2
      (KPNFIRFamide), was isolated and characterized from acid ethanol extracts of the
      free-living nematode, Panagrellus redivivus. Whole-worm extracts contained > or =
      9 pmol KPNFIRFamide/g wet weight. A synthetic replicate of this peptide induced a
      rapid relaxation of tone and inhibited spontaneous contractility in isolated
      innervated and denervated body-wall muscle strips of the parasitic nematode,
      Ascaris suum. KPNFIRFamide (0.1 nM) induced measurable relaxations in 50% of the
      muscle preparations examined. Concentrations > or = 0.3 nM induced relaxation in
      100% of muscle preparations examined. The relaxation was short-lived at
      concentrations of peptide > or = 1 microM and displayed a profile typical of
      receptor desensitization. These data suggest the occurrence of a closely related
      peptide in A. suum and add further evidence to the concept of primary structural
      conservation of FaRPs within the nematodes.

PMID- 7716081
TI  - Immunohistochemical localization of cathepsin B in neoplastic human prostate.
AB  - Cathepsin B (CB) has been shown to degrade extracellular matrix (ECM) proteins,
      and has been reported to be involved in invasion and metastasis of several types
      of solid organ tumors in human and animals, but CB has not been studied in human
      prostate cancer (CAP). Our objective was to determine the CB protein
      immunostaining pattern in CAP and to correlate the immunostaining with the degree
      of malignancy as reflected in the Gleason grading system. We used two types of CB
      antibodies (namely, monospecific, polyclonal antibodies to human liver CB
      prepared in rabbits, and polyclonal antibody produced in sheep) to establish CB
      localization patterns in neoplastic prostate. Our analysis showed a heterogeneous
      CB immunostaining pattern in the neoplastic human prostate. CB immunostaining
      occurred in many, but not all, of the neoplastic columnar/cuboidal cells of acini
      and isolated cells, i.e., in small ragged glands and clusters (groups) of
      invasive cells in the prostatic stroma. We have shown that, in general, there was
      a positive correlation of the intensity of CB immunostaining with the Gleason
      histologic score (or Gleason grade sum) tumors, i.e., from the lowest scores
      through score 8, but many of the tumors with scores 9 and 10 showed little CB
      immunostaining. Our study indicated that the increased CB immunostaining in the
      Gleason grade sum 5-8 tumors may be associated with increased degradation of ECM,
      but not in 9 and 10 despite the fact that the latter tumors are more malignant
      clinically. In well-differentiated tumors, fewer CB immunostaining cells were
      present than the moderately-differentiated tumors. In other words, most of the
      stromal invasion of the prostatic ECM occurred in tumors of Gleason grade sums 5
      8. We suggest that CB immunostaining might be a useful method to assess stromal
      invasion of prostatic carcinoma, especially in the higher grade tumors.

PMID- 7716078
TI  - Hexarelin, a potent GHRP analogue: interactions with GHRH and clonidine in young
      and aged dogs.
AB  - The GH-releasing activity of hexarelin was evaluated in unanesthetized young and
      aged dogs. Hexarelin (15.6-250 micrograms/kg, i.v.) significantly stimulated GH
      secretion in a dose-dependent fashion in dogs of both age groups. The ability of
      hexarelin to potentiate the GH-releasing effect of GHRH (2 micrograms/kg, i.v)
      and clonidine (4 micrograms/kg, i.v.) was then tested. Hexarelin strikingly
      potentiated the effect of GHRH both in young and aged dogs, whereas it
      potentiated the effect of clonidine in young dogs only. Because clonidine acts on
      the hypothalamus to release GHRH, its failure to synergize with hexarelin in aged
      dogs is likely due to an age-related impairment of GHRH-secreting neurons.

PMID- 7716083
TI  - Prolactin specifically increases pyruvate dehydrogenase E1 alpha in rat lateral
      prostate epithelial cells.
AB  - Prolactin is an important regulator of prostate citrate production. In rats this
      regulatory effect of prolactin is specific for lateral prostate, and has no
      effect on either ventral or dorsal prostate. The mechanisms by which prolactin
      regulates prostate citrate production have not been elucidated. Two key
      regulatory enzymes involved in citrate synthesis by prostate epithelial cells are
      mitochondrial aspartate aminotransferase (mAAT) which provides oxalacetate, and
      PDH E1 alpha (pyruvate dehydrogenase) which provides acetyl CoA for citrate
      synthesis. Our previous studies demonstrated that prolactin regulates mAAT.
      However, an increase in citrate synthesis would require an increase in both
      oxalacetate and acetyl CoA. Therefore, we investigated the possibility that
      prolactin might also regulate PDH E1 alpha in LP epithelial cells. The present
      studies demonstrate that prolactin administration (1 mg/rat) to rats resulted in
      an increased level of E1 alpha in LP epithelial cells within 6 hr, but had no
      effect on the E1 alpha level of VP epithelial cells. In vitro studies
      demonstrated that exposure of freshly prepared LP epithelial cells to prolactin
      (0.1-1.0 microgram/ml) resulted in increased levels of E1 alpha. Prolactin had no
      effect on either VP or DP epithelial cells. The stimulatory effect of prolactin
      on E1 alpha was inhibited by actinomycin and cycloheximide, thereby indicating
      that prolactin stimulated the biosynthesis of E1 alpha. The studies reveal that
      prolactin specifically stimulates E1 alpha levels of LP epithelial cells, whereas
      testosterone specifically stimulates E1 alpha levels of VP epithelial cells. At
      this time, we propose that the effects of prolactin and testosterone involve
      increased expression of the E1 alpha gene of LP and VP epithelial cells,
      respectively.

PMID- 7716086
TI  - Erectile dysfunction. Are you prepared to discuss it?
AB  - Erectile dysfunction is more common than previously thought in men older than 40
      years, perhaps because contributing medical risk factors increase with age. The
      medical history is of prime importance in outlining these factors, the most
      common of which are diabetes, hypertension, and smoking. Nocturnal penile
      tumescence and rigidity testing with a portable home monitor may be helpful in
      determining whether the cause of erectile dysfunction is primarily organic or
      psychological. Specific therapeutic measures include sex therapy, psychotherapy,
      treatment for alcohol or tobacco dependency, replacement of offending
      medications, improved glycemic control, constriction rings, vascular surgery,
      androgen replacement therapy, bromocriptine mesylate (Parlodel), and thyroid,
      adrenal, or pituitary replacement therapy. Nonspecific therapies include
      yohimbine hydrochloride (Yocon), use of vacuum tumescence devices, intracorporeal
      injections, and penile implants.

PMID- 7716084
TI  - Growth inhibition of androgen-insensitive human prostate carcinoma cells by a 19
      norsteroid derivative agent, mifepristone.
AB  - Mifepristone, also known as RU 486, is a 19-norsteroid derivative. Currently,
      mifepristone is being tested in clinical trials on meningioma and breast cancer.
      In this study we analyzed whether mifepristone could inhibit the growth of human
      prostate cancer cells including androgen-insensitive (PC-3 and DU145) and
      androgen-sensitive (LNCaP) cell lines. At 1-nM concentration, mifepristone
      exhibited a marginal stimulatory action on LN-CaP and PC-3 cells. Nevertheless, a
      dose-dependent growth inhibition on those same cell lines was observed at
      concentrations of 1 microM and 10 microM. Twenty-day exposure to the clinically
      achievable concentration of 1 microM mifepristone resulted in consistent
      inhibition of all three cell lines studied. Furthermore, this in vitro growth
      inhibition was reflected in an in vivo nude mouse system. Mifepristone at the
      dosage of 4 mg/100 g body weight completely suppressed the growth of PC-3 tumors
      for 21 days, although this was followed by a growth rate similar to that of the
      control tumor. To understand the possible mechanism of mifepristone inhibition,
      PC-3 cells were exposed to mifepristone in comparison with dexamethasone (Dex),
      progesterone, and 5 alpha-dihydrotestosterone (DHT), each at 1-microM
      concentration. The results demonstrated that while both DHT and Dex alone had
      essentially no effect on cell growth, progesterone alone resulted in a 20% growth
      inhibition, while mifepristone had more than 60% inhibition with a 16-day
      exposure. At an equal concentration, the degree of growth inhibition of PC-3
      cells by mifepristone or progesterone was partially diminished by simultaneous
      exposure to Dex. In conclusion, our results demonstrated that the growth of
      androgen-insensitive prostate cancer cells can be directly inhibited by
      mifepristone in cultures. This in vitro inhibition is reflected in xenografted
      tumors.

PMID- 7716082
TI  - Growth inhibition of human prostate tumor cells by an agonist of gonadotrophin
      releasing hormone.
AB  - The effect of [D-Leu6,des-Gly-NH2(10),Proethylamide9]-GnRH, leuprolide, was
      determined for the human primary prostate tumor cell line ALVA-31 by in vitro
      mitogenic assays. Prostate tumor cell proliferation was inhibited up to 50% by
      leuprolide. Inhibition was not observed in parallel cultures treated with other
      low molecular weight bioactive peptides. The incorporation and metabolic
      reduction of testosterone was not affected by concentrations of leuprolide that
      were inhibitory in the mitogenic assay. Specific high-affinity binding of 125I
      labeled leuprolide was also demonstrated on intact tumor cells with an estimated
      effective median dose (ED50) of < 1 x 10(-9)M. Inhibition of prostate tumor
      growth was further demonstrated in Balb/c athymic intact and castrate male mice
      bearing ALVA-31 tumor xenografts following chronic administration of leuprolide.
      These data clearly demonstrate that leuprolide can inhibit the growth of a human
      prostate carcinoma cell line. Studies conducted in castrate animals further
      suggest an alternative mechanism of growth inhibition that appears to be
      independent of the suppression of steroid hormone biosynthesis by LHRH analogues.

PMID- 7716085
TI  - Physical examination of substance abusers. How to gather evidence of concealed
      problems.
AB  - How can physicians make appropriate treatment decisions in substance abusers who
      have serious medical illness, especially when patients may not offer the
      information needed? Drs Westreich and Rosenthal summarize common physical
      findings that suggest abuse of specific substances. Recognizing these signs
      allows physicians to reliably diagnose chemical use, leads to improve outcomes,
      and lends weight to recommendations for substance-abuse therapy.

PMID- 7716087
TI  - Migraine and women. The link between headache and hormones.
AB  - Levels of sex hormones fluctuate throughout the female life cycle, and these
      fluctuations may trigger, intensify, or alleviate migraine. Drugs can be used
      both preventively and therapeutically to combat the headache that results in some
      women from such fluctuations. Effective prophylactic agents include beta
      blockers, antidepressants, calcium channel blockers, and hormones. Nonsteroidal
      anti-inflammatory drugs, ergotamine and its derivatives, and narcotics are among
      the abortive therapy options. Pharmacologic management of migraine in pregnant
      women must be conservative because of the risks of injury and dependence to the
      fetus and newborn.

PMID- 7716088
TI  - Acute lower gastrointestinal bleeding. A guide to initial management.
AB  - Initial assessment of any patient with acute gastrointestinal bleeding includes
      thorough history taking and physical examination, with special attention to
      orthostatic changes in vital signs as a guide to severity of blood loss. The next
      crucial step is exclusion of massive upper gastrointestinal hemorrhage. Once that
      is accomplished, a lower gastrointestinal source should be sought. Diagnostic
      options include bleeding scans, colonoscopy, and angiography. The latter two
      measures confer therapeutic advantages, especially for diverticular disease and
      angiodysplastic lesions, which are the most common causes of acute lower
      gastrointestinal bleeding.

PMID- 7716090
TI  - Equal time for the AMA.

PMID- 7716089
TI  - Equal time for the AAFP.

PMID- 7716091
TI  - Pulmonary tuberculosis. Is resurgence due to reactivation or new infection?
AB  - Spread of tuberculosis consists of three phases: In the transmission phase,
      Mycobacterium tuberculosis is transferred from a source of a host via
      aerosolization of respiratory secretions. During the infective phase, the
      organism establishes itself within the lung of the new host. In the pathogenetic
      phase, organism- and host-related mechanisms bring about clinical disease. In the
      past, the vast majority of cases of tuberculosis in the United States were
      assumed to be reactivation of dormant disease. However, the pathogenesis has
      increasingly shifted to progressive primary disease. This shift may be due to the
      low endogenous resistance to tuberculosis in native-born Americans. In addition,
      various social problems, especially in large cities, favor person-to-person
      transmission. Infectivity of M tuberculosis itself may be increasing as strains
      resistant to multiple agents become more common.

PMID- 7716092
TI  - Arthritis of recent onset. A guide to evaluation and initial therapy for primary
      care physicians.
AB  - Correct early diagnosis of acute and recent-onset arthritis is important to
      prognosis. The erosive damage done by rheumatoid arthritis occurs earlier in the
      disease course than previously realized, and more specific therapies to minimize
      damage are becoming available. Also, arthritis may be the initial clue to a
      serious systemic disease. Determining whether one, several, or many joints are
      affected can narrow the diagnostic possibilities. Arthrocentesis and synovial
      fluid testing provide much information and should be done at initial evaluation
      if possible. The presence or absence of fever, rash, family history of joint
      disease, and exposure to infective organisms can further direct diagnostic
      studies and treatment. In general, to avoid masking clues, drug therapy should be
      delayed for mild symptoms until diagnosis is complete.

PMID- 7716094
TI  - Systemic lupus erythematosus. Recognizing its various presentations.
AB  - Systemic lupus erythematosus (SLE) is a multisystem disease that predominantly
      affects women. Probable causative factors include genetic predisposition,
      complement deficiencies, persistence of antigen, drugs, and environmental
      factors. The widely varying presentations of SLE include skin, musculoskeletal,
      cardiovascular, renal, pulmonary, gastrointestinal, neuropsychiatric, systemic,
      hematologic, and immunologic manifestations. Milder symptoms can be managed with
      nonsteroidal anti-inflammatory drugs and antimalarial agents. Corticosteroids and
      cytotoxic drugs are given in more severe disease.

PMID- 7716093
TI  - Laboratory tests for rheumatic diseases. When are they useful?
AB  - Because negative tests often do not exclude a rheumatic disease and positive
      tests do not always diagnose it, judicious use of laboratory testing in patients
      with suspected rheumatic disease is essential. The final diagnosis must be made
      clinically. However, when the tests are used in conjunction with clinical
      manifestations, they may help differentiate the numerous rheumatic disorders, and
      they may also be of value in monitoring activity of the disease.

PMID- 7716095
TI  - Psoriatic arthritis. Diverse and sometimes highly destructive.
AB  - Psoriatic arthritis is an inflammatory arthritis with diverse clinical
      manifestations. Certain subsets of patients tend to run a more severe course of
      erosive disease. A few points are noteworthy: When a diagnosis of psoriatic
      arthritis is being considered, ask if there is any family history of psoriasis
      and search for skin lesions in all parts of the body, including the scalp, ears,
      and genital and anal areas. Rule out septic arthritis even in a patient with an
      established diagnosis of psoriatic arthritis, especially if the presentation is
      monarticular. In cases of fulminant disease, consider checking for HIV infection.
      Pharmacologic therapy and physical rehabilitation are used in psoriatic
      arthritis. Mild cases can be controlled with use of nonsteroidal anti
      inflammatory drugs; in more severe cases, treatment with immunosuppressive or
      disease-modifying agents is needed.

PMID- 7716096
TI  - Antidepressants: perspectives in primary and secondary health care. Proceedings
      of a meeting held in London. 1 December 1993.

PMID- 7716097
TI  - The economic evaluation of depression.

PMID- 7716098
TI  - Juggling cost and benefit in the long-term treatment of depression.

PMID- 7716099
TI  - The prescribing of antidepressants in general practice: the use of PACT data
      (brief report).

PMID- 7716100
TI  - Medico-legal aspects of suicide--a clinical perspective.

PMID- 7716101
TI  - Medico-legal aspects of antidepressant prescribing: a comment.

PMID- 7716102
TI  - Antidepressants and overdoses.
AB  - A review of the problems connected with antidepressant overdosage shows that the
      tricyclic drugs are associated with a high morbidity and mortality. Any strategy
      for suicide reduction must include a policy for prescribing drugs with a lower
      overdose mortality.

PMID- 7716103
TI  - Bacterial adhesion to respiratory mucosa and its modulation by antibiotics at sub
      inhibitory concentrations.
AB  - Respiratory infections develop after contact and successive adhesion of micro
      organisms to airway mucosa. In fact, the bacterial adhesins are able to interact
      with a 'lock and key' mechanism with the analogous structures on epithelial
      surfaces when permissive conditions occur. It was observed that antibiotics at
      subinhibitory concentrations (sub-MICs) can modify bacterial ability of adhesion
      to host cells, in various ways. Bacterial adhesion is generally inhibited by
      antibiotics that, at these concentrations, do not kill bacteria but can change
      the surface architecture of the micro-organisms.

PMID- 7716104
TI  - Apoptosis, senescence, immortalization and cancer.

PMID- 7716105
TI  - Supramaximal decrease of sulphonylurea-induced accumulation of sodium in
      pancreatic islets.
AB  - Sodium was measured in beta-cell-rich pancreatic islets of mice under steady
      state conditions or after 6 min of exposure to 1 mM ouabain. The islet content of
      sodium increased when 100 microM tolbutamide or 1 microM glipizide were added to
      an albumin-containing (1 mg ml-1) medium, but remained unaffected at 10-fold
      higher concentrations. Both sulphonylurea compounds promoted the uptake of Na+ in
      the presence of ouabain. Whereas tolbutamide was stimulatory at 10 microM or
      above in a medium containing 10 mg ml-1 albumin, only 0.1 microM was required in
      the absence of albumin. In the latter situation there was a reduction of the
      stimulatory action with increase of the tolbutamide concentration from 100 to
      1000 microM. The inhibitory component in the sulphonylurea action on the Na+
      uptake was particularly impressive with glipizide, maximal stimulation being
      reached at 10 microM in the presence of 1 mg ml-1 albumin. Diazoxide (400 microM)
      modified the glipizide action on Na+ uptake, making 1000 microM stimulatory
      instead of 1 microM. The latter concentration of glipizide became inhibitory
      after removal of K+. Glipizide stimulated the Na+ uptake both at low and high
      concentrations in a medium deficient in Ca2+ or when the cotransport of Na+, K+
      and Cl- was blocked by 20 microM bumetanide. The observation that the
      sulphonylurea-induced islet accumulation of sodium is diminished at supramaximal
      concentrations reinforces existing arguments for additional effects of high
      concentrations of hypoglycemic sulphonylureas.

PMID- 7716106
TI  - A simplified in vitro preparation of the corpus cavernosum as a tool for
      investigating erectile pharmacology in the rat.
AB  - This work describes a simple technique for the assessment of corpus cavernosum
      function in a species, the rat, representing a convenient model for basic
      research. We obtained measurable and reproducible responses to different
      pharmacological agents as well as to electrical field stimulation. In view of the
      present results we conclude that isolation of the erectile tissue together with
      the septum may constitute a valuable experimental tool for investigating both
      local erectile mechanisms and the action of drugs, in the rat corpus cavernosum.
      Data obtained in the presence of N-nitro-L-arginine and methylene blue further
      reinforce the concept that nitric oxide may be involved in the process of
      erection in the rats as well as in other animal species.

PMID- 7716107
TI  - Extracellular calcium and magnesium interfere differently with actin
      polymerization in human and rabbit neutrophils.
AB  - This study attempts to elucidate, in man and rabbit neutrophils, the relevance of
      extracellular Ca2+ and Mg2+ to actin polymerization induced by fMLP, a
      chemotactic peptide. The presence of as little as 0.2 mM divalent ions in the
      cell suspending medium inhibits the actin polymerization in rabbit neutrophils,
      and partially reduces it in human neutrophils.

PMID- 7716108
TI  - Thiocyanate levels of mainly dietary origin in serum and urine from a human
      population sample in Port Harcourt, Nigeria.
AB  - Thiocyanate levels were determined in serum and urine samples obtained from a
      human population sample of healthy non-smoking volunteers (aged between 14 and 30
      years) of both sexes known to eat gari-based meals at least once a day. The
      samples were collected before and 3-4 hours after a gari- or rice-based meal. The
      values obtained before the test meals showed a wide variation, ranging between
      39.20 +/- 1.95 to 160.95 +/- 8.06 mumol/l of serum, and 81.92 +/- 9.78 to 294.01
      +/- 14.70 mumol/l of urine. For each volunteer, the serum and urine thiocyanate
      were affected by the test meals. Average increases of 18 and 20% were observed
      for serum and urine thiocyanate, respectively, following a gari-based meal. A
      rice-based meal produced, on the average, 10% decrease in both serum and urine
      thiocyanate. No significant effect of sex or age on the thiocyanate levels was
      observed. The gari samples used in the study, as well as random samples from the
      locality of study, had no detectable thiocyanate but contained between 0.013 and
      0.015 mg cyanide per kg of gari. These findings indicate that conversion to
      thiocyanate is a significant pathway in the metabolism of HCN and contributes
      significantly to thiocyanate found in body fluids and tissues of man. In
      addition, support is provided for the possible involvement of the sulphur
      transferases in the process of cyanide detoxication.

PMID- 7716109
TI  - Acceptability and viscosity of low cost home processed supplementary foods
      developed for pre-school children.
AB  - Four supplement mixtures using whole wheat, pearl millet, bengal gram, green
      gram, groundnuts and amaranth leaves were developed employing roasting and
      malting techniques. Malting used in the formation of the supplements reduced
      significantly hot paste viscosity of all the four supplements and increased their
      nutrient density per unit volume. The results of organoleptic trials conducted on
      rural mothers revealed that taste, texture, colour, aroma, appearance and overall
      acceptability of all the four supplements were excellent with mean scores of
      overall acceptability (9.77, 9.33, 9.11 and 8.75) for supplements I, II, III and
      IV, respectively. Children did not develop any GIT disorders after consuming the
      products. Trained panelists found all the four supplements acceptable as
      indicated by Nine point hedonic scale.

PMID- 7716110
TI  - Consumer acceptability of stiff porridge based on various composite flour
      proportions of sorghum, maize and cassava.
AB  - A study was conducted to determine consumer acceptable proportions of flours in
      sorghum (var. serena) and maize or sorghum, maize and cassava composite flours.
      Breeder's serena flour extracted at 75 percent was mixed at various proportions
      with maize or with maize and cassava to constitute composite flours. The various
      composite flours were made into stiff porridge and presented to a group of
      panellists for sensory evaluation. The evaluation was conducted by scoring on a
      hedonic scale of 0-5 for poor to excellent, respectively, for the parameters
      colour, texture, flavour, taste and overall acceptability. The responses were
      analysed statistically. Alternatively the panellists were allowed to eat ad-lib
      any of the presented samples which appealed to them. The results demonstrated
      that slight incorporation (< 10%) of sorghum (var. serena) to maize flour leads
      to reduction in consumer acceptability. However, increased incorporation of
      sorghum in excess of 10 percent leads to no significant decrease in consumer
      acceptability until a level of 30 percent incorporation is exceeded. In sorghum,
      maize, cassava composite flours the formulation of 30:40:30, respectively, was
      found to be most acceptable. It is suggested that at this combination of flours
      desirable textural characteristics of the porridge overrides other factors in
      contributing to its acceptability.

PMID- 7716111
TI  - Acceptability of wheat-sorghum composite flour products: an assessment.
AB  - The acceptability of sorghum as human food has been a problem in Tanzania even in
      regions showing promising potential for its production and utilization. Reasons
      given for low acceptability of sorghum products as human foods include unpleasant
      colour, aroma, mouthfeel, taste, unpleasant aftertaste and stomachfeel. An
      acceptability test of selected sorghum products was, therefore, conducted in the
      Department of Food Science and Technology, Sokoine University of Agriculture,
      Morogoro, Tanzania. The objective of the test was to determine consumers'
      preference for the following wheat-sorghum composite flour products: bread and
      buns or 'maandazi'. The products were prepared using sorghum flour composited
      with wheat flour in the following proportions: 100% brown sorghum flour (standard
      products); and 80:20%; 60:40%; 40:60% and 20:80% for wheat/sorghum (white and
      brown) composite flours. Results indicated that in the case of composite flour
      bread, preference for the product improved as the amount of sorghum flour
      decreased. In the case of buns or 'maandazi' the 100% sorghum flour products of
      both white and brown were equally preferred. Buns prepared from 100% sorghum
      flour of white and brown varieties showed promising potential in the improvement
      of the acceptability of sorghum products. Taking advantage of such products,
      especially in villages, could enhance sorghum utilization in rural communities.

PMID- 7716112
TI  - Leaf protein content and yield of some Indian legumes.
AB  - Eighty three leguminous species including crop plants, weeds and trees have been
      screened for their content of leaf protein as well as extractabilities of leaf
      protein, total N and protein N. Leaves of Crotalaria sericea Retz. showed the
      highest values for extractabilities of LP and protein N as well as total N
      content in leaf protein.

PMID- 7716114
TI  - Tannins in utilization of sorghum grains in Burkina Faso.
AB  - The study of thirty sorghum varieties used for food in Burkina Faso showed a
      relationship between tannin level and utilization of sorghum grain. High tannin
      level varieties (more than 0.2%) are generally used for local alcoholic drink,
      instead low tannin level varieties (under 0.2%) are used for cooking and for non
      fermented drinks.

PMID- 7716113
TI  - Chemical, nutritional and technological characteristics of buckwheat and non
      prolamine buckwheat flours in comparison of wheat flour.
AB  - Chemical, nutritional, and technological characteristics of buckwheat and non
      prolamine buckwheat flours in comparison to wheat for celiac patients use have
      been studied. The results suggested the following conclusions: the 56.5%
      extraction value for flour obtention is considered good; the buckwheat flour
      presents methionine and cystine as first limiting amino acids followed by
      threonine as the second limiting amino acid; the buckwheat flour presents higher
      content of lysine amino acids than the wheat flour; the buckwheat flour is
      superior to the wheat flour regarding iron, copper, and magnesium minerals; the
      buckwheat flour does not present haemagglutinin activity and the tannin content
      is negligible. Rheological assays indicate that the buckwheat flour does not
      contain gluten.

PMID- 7716115
TI  - Effect of processing and storage on the ascorbic acid (vitamin C) content of some
      pineapple varieties grown in the Rivers State of Nigeria.
AB  - Ascorbic acid contents of the juice of four different pineapples species grown in
      the Rivers State of Nigeria were determined before and after storage of whole
      pineapple and processing and storage of the juice for two months. Ascorbic acid
      of the fresh juice ranged from 22.5 mg to 33.5 mg/100 g sample. After storage at
      room temperature (30-32 degrees C) of whole pineapple for two weeks, ascorbic
      acid was reduced to between 59 and 65 percent of the fresh juice. Processing the
      juice by pasteurisation reduced the ascorbic acid to between 28 and 46 percent
      while storage in plastic bottles for two months further reduced the ascorbic acid
      content to between 10 and 21 percent.

PMID- 7716116
TI  - Proximate composition, energy content and physiochemical properties of Afzelia
      africana and Brachystegia eurycoma seeds.
AB  - The proximate composition, energy content and physiochemical properties of
      Afzelia africana and Brachystegia eurycoma seeds were determined. The bulk
      density, reconstitutability, foam properties and emulsification properties of
      flour samples in water, 1% saline and 1% alkali were studied. There were no
      significant differences (p > or = 0.05) in the proximate composition of seeds
      from different agroclimatic zones. The energy content of seeds were comparable to
      that of other legume seeds (5.7 kcal/g for A. africana and 4.5 kcal/g for B.
      eurycoma seeds). Foam properties of B. eurycoma seeds were found to be better
      than that of A. africana seeds in terms of foam volume and stability.
      Emulsification properties of B. eurycoma seeds were also found to be better than
      A. africana seeds suggesting that B. eurycoma seeds would be more efficient in
      food systems requiring the formation of stable foams and emulsions. Protein
      solubility in alkali was found to be better than in water and in 1% saline. The
      bulk densities and reconstitution indices of flour samples from the two seeds
      were found to be similar.

PMID- 7716117
TI  - Utilization of cassava peels as substrate for crude protein formation.
AB  - Mash prepared from cassava peels was inoculated with either Sacchromyces
      cerevisiae or Candida tropicalis and then left to ferment for 7 days. Chemical
      analysis of the fermented mash showed substantial increase in crude protein
      content and decrease in carbohydrate content of the mash. The results also
      revealed slight increases in the ash, fibre and lipid content of the fermented
      mash. It was further observed that, when the mash was supplemented with inorganic
      nitrogen sources (urea, ammonium sulfate or sodium nitrate) before commencement
      of fermentation, the amount of crude protein formed was almost doubled. This
      enhanced crude protein production was highest in the mash supplemented with urea.
      Temperature of 30 degrees C, pH of 5.5 and moisture concentration of 130% were
      found to be optimum for crude protein formation by the organisms growing on the
      mash.

PMID- 7716118
TI  - Blanching of green bean (Phaseolus vulgaris).
AB  - Experiments with one and two steps blanching of green beans have been carried
      out. Inactivation of the peroxydase requires more heating than inactivation of
      the enzymes which gives rise to off flavour from aldehydes. When blanching for
      about one minute to inactivate lipoxygenase, aldehyde formation of flavour
      ceases. The content of vitamin C decreases during blanching according to a first
      order reaction. Since considerable loss of vitamin C occurs during blanching, the
      treatment time should be reduced to a minimum. During preblanching at 65-75
      degrees C and final blanching, chlorophyll is degraded to pheophytin and the
      surface colour expressed by the Hunter-values (-a/b) increases with time which
      means that the colour of the beans changes from green to yellow. The firmness of
      beans, which was measured by use of a tenderometer, decreases during blanching
      according to a first order reaction with 40 kcal/mole activation energy.
      Preblanching at 65-75 degrees C increases the firmness of the beans linearly with
      treatment time. This increase in firmness is stable after final blanching at 95
      degrees C and even after thawing of frozen beans.

PMID- 7716119
TI  - Characterization of oils and chemical analyses of the seeds of wild plants.
AB  - The Chemical compositions of the seeds of some wild plants have been
      investigated. The seeds of Hematostaphis berteri, Balanites aegytiaca and Ximenia
      americana contain high levels of oils with values in the range, 38.2-54.5% (w/w).
      The iodine values of the oils were determined and, for Ximenia americana, the
      value was high, i.e., 149.8 mg/100 g. The storage properties of the oil of
      Hematostaphis berteri were examined over a period of fifty six days by exposure
      to light at ambient temperature. The peroxide value of the oil over the period
      increased by 12-fold of its initial value of 27.5 mEq/kg, suggesting light
      susceptibility to photo-oxidative degradation. The proximate protein contents
      were low but the concentrations of mineral elements in the seeds examined were
      generally high, exceeding the values for the corresponding mesocarps by several
      orders of magnitude.

PMID- 7716121
TI  - Progress toward understanding the regulation of amniotic fluid volume: water and
      solute fluxes in and through the fetal membranes.

PMID- 7716120
TI  - Chemical and nutritional evaluation of two germplasms of the tribal pulse,
      Bauhinia racemosa Lamk.
AB  - Two germplasms of the tribal pulse, Bauhinia racemosa Lamk. viz., Ayyanarkoil
      Forest and Mundanthurai Wildlife Sanctuary, were analysed for proximate
      composition, total (true) seed proteins, seed protein fractions, amino acid
      composition, fatty acids, minerals and antinutritional factors. Crude proteins,
      crude lipids, ash and nitrogen free extractives constituted 19.84%, 9.52%, 3.31%
      and 60.65%, respectively in Ayyanarkoil Forest germplasm; whereas, in
      Mundanthurai Wildlife Sanctuary germplasm they constituted 19.31%, 8.94%, 3.81%
      and 61.30%, respectively. The caloric values were found to be 407.64 KCal
      (Ayyanarkoil Forest) and 402.90 KCal (Mundanthurai Wildlife Sanctuary)
      germplasms. Essential amino acids like isoleucine, tyrosine, phenylalanine and
      lysine were found to be high in the seed proteins of both the germplasms. The
      fatty acids, palmitic, oleic and linoleic acids, were found to be relatively
      higher in the seed lipids of both the germplasms. Both the germplasms seemed to
      be a rich source of calcium, potassium, magnesium, zinc, manganese and iron.
      Antinutritional substances like total free phenols, tannins, L-DOPA and
      phytohaemagglutinating activity also were investigated.

PMID- 7716122
TI  - Expression of the p53 tumour suppressor gene in human placenta: an
      immunohistochemical study.
AB  - Since human trophoblast undergoes extensive proliferation and exhibits invasive
      growth comparable to that of a malignant tumour, human placenta at various
      different stages of gestation was investigated immunohistochemically with the
      monoclonal antibody Ab-6 for expression of the p53 tumour suppressor gene. p53
      protein was detected in the nuclei of a few trophoblastic cells, almost all
      belonging to the cytotrophoblast and only very few to the syncytiotrophoblast, in
      nearly all specimens investigated (first trimester 10/10, second trimester 5/5,
      third trimester 4/5). First trimester trophoblast exhibited increased expression
      of p53 protein in the juxtastromal areas of cytotrophoblast cell islands and
      columns, that is, in areas where high proliferative activity and increased
      expression of the epidermal growth factor receptor have been described in the
      literature. Staining was also occasionally seen in trophoblast invading the
      myometrium. It is most likely that immunohistochemically detectable expression of
      p53 protein in the trophoblast is due not to mutation of the gene, as in
      malignant tumours, but rather to up-regulation of the p53 tumour suppressor gene,
      which could be a mechanism for controlling trophoblast proliferation.

PMID- 7716123
TI  - Classics revisited: Wilhelm (William) Th. Preyer: Specielle Physiologie des
      Embryo. pp. 644 (Grieben, Leipzig 1885).

PMID- 7716124
TI  - Molecular and Cellular Aspects of Peri-implantation Processes, Boston,
      Massachusetts 15-18 July 1994.

PMID- 7716125
TI  - Metabolic interrelationships of placenta and fetus.
AB  - Placental-fetal metabolic relationships are complex and dynamic. For example, the
      placenta consumes glucose as well as transports it to the fetus, thus regulating
      fetal glucose supply and fetal plasma glucose concentration. In turn, fetal
      plasma glucose concentration, which is also regulated by the relative rates of
      fetal glucose utilization and production (both also regulated by glucose-induced
      insulin secretion), regulates placental glucose consumption and the partition of
      uterine glucose uptake into placental glucose consumption and glucose transfer to
      the fetus. For amino acids, unique placental transport and metabolic processes
      determine the quality as well as the quantity of amino acids that enter the fetal
      circulation. In turn, this unique qualitative and quantitative supply of amino
      acids provides a variety of regulatory controls over a diverse set of
      developmental metabolic processes as well as fetal protein turnover and growth.
      Similarly, complex placental lipid metabolism and transport affect the quality
      and quantity of lipids delivered to the fetus and thus the composition and amount
      of lipids in fetal tissues. Clearly, placental and fetal metabolic
      interrelationships represent vital and unique processes that control and
      determine many aspects of fetal development.

PMID- 7716126
TI  - Characterization of cell polarity and epithelial junctions in the choriocarcinoma
      cell line, JAR.
AB  - In the placenta the trophoblast cell layer separates maternal and fetal
      circulations and is involved in the active transport of selected substances
      across this barrier. We have used the JAR choriocarcinoma cell line to study
      aspects of trophoblast membrane transport. To determine whether JAR cells could
      be used in studies of vectorial transepithelial transport it was necessary to
      determine whether these cells were polarized and assembled tight junctions. In
      the present study we investigated JAR cells using a range of markers for specific
      cell surface domains combined with confocal laser scanning microscopy. Freshly
      isolated cells initially formed a confluent epithelial monolayer with recruitment
      of a tight junction-associated protein, ZO-1, and a cell adhesion molecule, E
      cadherin, to the surface at sites of cell-cell contact. They did not, however,
      display cell surface polarization, as NaK-ATPase was not segregated in the
      basolateral domain, and a differentiated apical cell surface was not assembled.
      The monolayer stage was also unstable, as continued proliferation resulted in the
      formation of multilayered aggregates where ZO-1 and E-cadherin were lost from the
      cell surface. These results suggest that the JAR cell line is unlikely to be a
      suitable model for studies of transepithelial transport in the placenta.

PMID- 7716127
TI  - Trophoblast differentiation during formation of anchoring villi in a model of the
      early human placenta in vitro.
AB  - In human implantation sites, formation of the cytotrophoblast shell and
      morphogenesis of anchoring villi occur during the 2nd and 3rd week of pregnancy.
      When placental villous tissue from 8-12 weeks was co-cultured with decidua
      parietalis, morphogenetic changes were observed specifically at sites of
      heterotypic contact, generating structures that closely resembled first trimester
      anchoring villi. Local breakdown of the syncytium and cytotrophoblast
      proliferation occurred, producing columns of cytotrophoblast. These columns
      showed complex changes of cell surface phenotype that replicate precisely the
      extravillous trophoblast differentiation pathway seen in vivo, including
      induction of integrin alpha 5 beta 1, loss of integrin alpha 6 beta 4 and
      expression of the HLA class I framework epitope recognized by monoclonal antibody
      W6/32. Extracellular matrix components including laminin, collagen type IV,
      fibrin and fibronectin were detected in intercytotrophoblastic spaces in the
      nascent columns. Spreading over the surface of the decidua and infiltration by
      cytotrophoblast were observed. We conclude that: (i) fist trimester floating
      villi retain the capacity to differentiate into anchoring villi; (ii) contact
      with decidua stimulates local breakthrough of the syncytium and cytotrophoblast
      proliferation; (iii) the resulting cytotrophoblast columns show phenotypic
      changes characteristic of these structures in vivo; and (iv) parietal decidua is
      capable of supporting implantation site-specific changes in a manner similar to
      the basal decidua.

PMID- 7716128
TI  - The perivascular contractile sheath of human placental stem villi: its isolation
      and characterization.
AB  - Former studies have shown that fetal blood vessels of stem villi in the human
      placenta are enclosed by sheaths of presumed contractile cells. Efforts to prove
      the contractility of these sheaths by isometric and biochemical investigations
      still suffer from the difficulty of differentiating between extravascular and
      vascular (media) contractile cells. The present study describes a method for the
      selective dissection of perivascular tissue sheaths in stem villi of
      approximately 2-4 mm thickness, which contained abundant alpha-actin
      immunoreactive cells and were free of adherent vascular smooth muscle cells.
      These extravascular contractile cells are part of the 'fibrous paravascular
      sheath', which, in placental pathology, is used as an index of maturity. To
      emphasize the high number of contractile cells and their location within this
      sheath, we propose the common term perivascular contractile sheath (PVCS). The
      isolation method offers the possibility of selectively investigating the
      contractile forces of the PVCS and of obtaining more insight into its functional
      role.

PMID- 7716129
TI  - Selenoprotein P expression in liver, uterus and placenta during late pregnancy.
AB  - To identify genes that exhibit increased expression in the placenta during late
      pregnancy, the technique of differential cDNA library screening was used to
      isolate a clone subsequently identified as the 3' untranslated region of the
      mouse selenoprotein p gene. Random primed radiolabelled cDNA probes were
      constructed from this clone and these probes were used to conduct Northern
      hybridizations against total RNA purified from mouse placenta, liver (maternal
      and fetal) and uterus collected sequentially during the latter third of
      pregnancy. Signal is present in the placenta and beginning 4 days before birth,
      the level of message increases, reaching maximal levels at term. The level of
      expression in the placenta at maximum is approximately 25 per cent of that
      observed in adult liver. In liver obtained from pregnant females, the level of
      message is increased compared to nonpregnant adults, but returns to normal
      shortly after birth. Message is also found in the fetal liver beginning at 4 days
      before birth and exhibits a pattern of expression similar to the placenta. The
      similarity of expression observed in fetal liver and placenta suggests a
      coordinated regulation of expression of this gene in these tissues. There is a
      minimal amount of signal present in the uterus and the expression does not appear
      to vary. We speculate that selenoprotein p may play a role in the transplacental
      transport of selenium to the fetus during late pregnancy.

PMID- 7716130
TI  - In vitro effect of antiphospholipid antibody-containing sera on basal and
      gonadotrophin releasing hormone-dependent human chorionic gonadotrophin release
      by cultured trophoblast cells.
AB  - Our objective was to evaluate whether antiphospholipid antibody-containing sera
      could play a regulatory role in signal transduction induced by gonadotrophin
      releasing hormone (GnRH) when incubated with normal human trophoblast cells. To
      test this hypothesis we established an in vitro placental culture system in which
      GnRH addition in the presence of normal human serum resulted in a significant
      increase in human chorionic gonadotrophin (hCG) secretion. When GnRH was added to
      the culture medium with antiphospholipid antibody-containing sera, the hCG
      increase was inhibited. These results suggest the possibility that
      antiphospholipid antibody-positive sera can exert their effect on GnRH-induced
      signal transduction. Further studies are needed to explain their exact site of
      action.

PMID- 7716131
TI  - Gastric inhibitory polypeptide and gastric acid secretion in pregnant rats.
AB  - The effects of pregnancy on the basal and pentagastrin-stimulated gastric acid
      secretion and the level of plasma gastric inhibitory polypeptide (GIP) in rats
      were studied on pentobarbital-anaesthetized non-pregnant rats and rats in the
      1st, 2nd, or 3rd week of gestation. Acid output was determined by titration of
      the gastric perfusate. Basal secretion was collected for 45 min before a 30 min
      infusion of pentagastrin (8 micrograms/ml/300 g body weight). Concentration of
      plasma GIP was measured by a radioimmunoassay (RIA). The immunoreactivity of GIP
      like substance in the extract of the rat placenta collected from the rat at day
      21 of gestation was examined by RIA. The biological activity of GIP-like
      substance in the rat placenta extract was tested by the reduction of pentagastrin
      stimulated gastric acid secretion in male rats. The basal level of gastric
      secretion was higher in late pregnancy as compared with the non-pregnant rats.
      Pentagastrin induced a greater increase of gastric acid secretion in early but
      not late pregnant rats as compared with the non-pregnant animals. The basal and
      post-pentagastrin level of plasma GIP was higher in rats in late pregnancy. Both
      immunoreactivity and biological activity of GIP exist in the rat placenta
      extract. These results suggest that the normalization of gastric acid secretion
      in late pregnant rats is at least in part due to the production of GIP-like
      substance from placenta.

PMID- 7716132
TI  - Human term placental capillary endothelial cell specialization: a morphometric
      study.
AB  - In the human placental capillary endothelium, two cell types have previously been
      described with different organelle distribution patterns. This observation was
      based on examination of cross-sectional profiles. It is known, however, that
      organelle distribution may vary in different parts of a cell. The present study
      was undertaken to estimate morphometrically the pattern of organelle distribution
      in normal term placental capillary endothelium. Ten normal term placentae were
      processed routinely for electron microscopy. The volume fractions of the
      different organelles were determined in both the perinuclear and peripheral parts
      of the cells. In addition, comparisons were made between endothelial cells at the
      site of vasculosyncytial membranes (VSM) and those forming the remainder of the
      capillary wall (non-VSM). Multifactor ANOVA showed there was a significant
      difference between the perinuclear and the peripheral parts in the volume
      fractions of mitochondria, rough endoplasmic reticulum, intermediate filaments,
      all these being more in the perinuclear region, whilst vesicles and cytosol were
      more prevalent in the peripheral parts. In contrast, there was no significant
      difference between the regions of VSM and the non-VSM except for the volume
      fractions of microfilaments which were higher in the non-VSM region.

PMID- 7716133
TI  - Different inhibitory effects of the newly developed CCK receptor antagonists
      FK480 and KSG-504 on pancreatic exocrine and endocrine secretion in the isolated
      perfused rat pancreas.
AB  - Cholecystokinin (CCK) receptor antagonists are shown to have therapeutic as well
      as preventive effects in some types of acute pancreatitis. However, there is a
      possibility that administration of CCK receptor antagonists with a high
      inhibitory potency on the endocrine pancreas to patients with acute pancreatitis
      exacerbates the associated glucose intolerance. In the present study we
      simultaneously examined the effects of the newly developed benzodiazepine
      derivative FK480 and proglumide-related antagonist KSG-504 on CCK octapeptide
      (CCK-8)-stimulated exocrine and endocrine function in the isolated perfused rat
      pancreas. FK480 and KSG-504 inhibited CCK-8-stimulated pancreatic juice flow,
      protein output, and insulin release in a dose-dependent manner. FK480 was
      approximately 10 times more potent than KSG-504 in inhibiting exocrine and
      endocrine secretion. Both antagonists inhibited CCK-8-stimulated insulin release
      more potently than exocrine secretion. FK480 caused a dose-dependent residual
      inhibition of exocrine secretion after its removal from the perfusate, whereas
      insulin release was only slightly impaired even at the highest dose. In contrast,
      termination of KSG-504 infusion resulted in an immediate increase in both
      exocrine and insulin responses without causing any residual inhibition. With
      regard to the residual inhibition, therefore, KSG-504 had no significant
      influences on exocrine and insulin release, whereas FK480 inhibited exocrine
      secretion more potently than insulin response. These results suggest that FK480
      might become a useful therapeutic agent for pancreatitis with respect to its long
      duration inhibitory effect on exocrine secretion and short-duration inhibitory
      effect on insulin release.

PMID- 7716134
TI  - Effect of a cholecystokinin (CCK) antagonist (CR 1505) on gene expressions of CCK
      and secretin in rat intestine.
AB  - The effects of intragastric administration of cholecystokinin (CCK) antagonist
      (CR 1505; 60-300 mg/kg/day) to rats for 3 days on the gene expressions of CCK and
      secretin, the plasma CCK immunoreactivity, and the CCK content in the intestinal
      mucosa were examined. CR 1505 increased the level of CCK mRNA in the intestine
      dose dependently to up to 1.6 times the level in control rats but did not affect
      the level of secretin mRNA. It also significantly increased the plasma CCK
      immunoreactivity and the amount of CCK extracted from intestine with acid dose
      dependently. CR 1505 tended to decrease the trypsin activity in the intestine.
      These results suggest that ingested CR 1505 increased the CCK mRNA level in the
      intestine.

PMID- 7716135
TI  - Differential effects of peptide YY, neuropeptide Y, and sigma ligands on neurally
      stimulated external pancreatic secretion in the rat.
AB  - The endocrine peptide YY (PYY) inhibits pancreatic secretion in animals and in
      man through indirect pathways. Neuropeptide Y (NPY), whose chemical structure is
      very close, displays similar effects. Recently, sigma ligands were shown to
      produce in vivo several neural pharmacologic effects that seemed
      indistinguishable from those of NPY. This might occur by interaction with the
      same (or closely related) receptors or by activation of a common final pathway.
      The purpose of the present work was to test whether PYY, NPY, and sigma agonists
      also display closely related activities on pancreatic secretion. The sigma
      ligands (+)-N-allyl normetazocine (d-NANM) and di(ortho-tolyl) guanidine (DTG)
      were used. Pancreatic secretion was stimulated by the centrally acting agent 2
      deoxyglucose (2DG) in anesthetized rats. The rats were also administered either
      an infusion of peptide (PYY: 25-250 pmol/kg/h, NPY: 75-750 pmol/kg/h), continued
      for 2 h, or a bolus injection of d-NANM (3 mg/kg) or DTG (1 mg/kg). In antagonist
      experiments, the dopamine and sigma antagonist haloperidol (1 mg/kg, i.v.), the
      adrenoceptor antagonists idazoxan (0.3 mg/kg, s.c.), prazosin (0.5 mg/kg, s.c.),
      propranolol (1 mg/kg, s.c.) and the opiate receptor antagonist naloxone (1 mg/kg,
      s.c.) were injected, 5 min before the peptide infusion had begun. Neither PYY nor
      NPY changed basal pancreatic secretion. PYY and NPY produced a dose-related
      inhibition of 2DG-stimulated pancreatic secretion. The observed inhibition after
      250 pmol/kg/h of PYY was volume, 78% (p < 0.01); bicarbonate, 84% (p < 0.01);
      protein, 78% (p < 0.01); whereas the physiologically relevant dose of 25
      pmol/kg/h induced approximately 30% inhibition of these variables.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7716136
TI  - Effect of alloxan on the endocrine function of human fetal islet-like cell
      clusters--an in vitro study.
AB  - We studied the effects of alloxan on insulin and glucagon secretion, islet
      insulin content, and morphology of human fetal islet-like cell clusters (ICCs).
      ICCs were derived after collagenase digestion and culture of pancreata from two
      fetuses. Culture medium (RPMI 1640) containing either 2.0 (low) or 11.1 (high) mM
      glucose was used during the alloxan exposure. Alloxan exposure lasted for 5 min
      at room temperature, with final concentrations of 0.3, 1, 3, 10, 30 and 100 mM.
      Medium samples were collected for hormone assays on days 0, 1, 2, 3, 6, and 10
      and islet insulin contents were measured on day 10 after alloxan treatment.
      Electron microscopy of ICCs was done 24 h after the drug exposure. Control ICCs
      steadily increased their insulin secretion during the whole study period. Alloxan
      concentrations above 0.3 mM significantly (p < 0.01) decreased insulin secretion
      at the low glucose concentration. High glucose protected beta cells from alloxan
      toxicity. There was no difference in islet insulin contents between alloxan
      treated and control cultures. Glucagon secretion by glucose media was not
      affected by alloxan exposure. All islet cells including beta cells remained
      intact in electron microscopy. The results suggest a block in insulin secretion
      by alloxan, but beta cells appear to recover at least partly in their insulin
      secreting capacity.

PMID- 7716138
TI  - Pseudocysts and pseudoaneurysms: surgical strategy.
AB  - Eight patients over an 8-year period required operation for spontaneous
      hemorrhage as a complication of a pancreatic pseudocyst. Three patients presented
      with abdominal pain or jaundice and bled in hospital while undergoing work-up.
      Four patients were admitted with upper gastrointestinal bleeding and one with
      intraperitoneal bleeding. Five patients were managed by pancreatic resection (two
      of the head and three of the tail) and three were managed by arterial ligation
      and internal drainage. There was one death (mortality rate, 12.5%). The first
      four patients in the series had their operations delayed secondary to a perceived
      need for further work-up or an inability to make an exact diagnosis of the
      bleeding site. All rebled, necessitating an emergency operation. The last four
      patients underwent an expedited workup and operation. Successful treatment of
      bleeding pancreatic pseudocysts requires good surgical judgment, especially when
      nonoperative methods fail or aren't applicable. The risk of recurrent hemorrhage
      is high, suggesting the need for immediate intervention once the diagnosis is
      made. Resection provides definitive control, although selected patients with
      easily accessible vessels may be managed more conservatively with ligation and
      drainage.

PMID- 7716137
TI  - Pancreatic stone protein and lactoferrin in human pancreatic juice in chronic
      pancreatitis.
AB  - Lactoferrin and pancreatic stone protein (PSP) are thought to be closely related
      to pancreatic stone formation in chronic pancreatitis. However, the results
      reported so far have not been conclusive. To reevaluate the pathological
      importance of PSP in chronic pancreatitis, compared to lactoferrin, levels of PSP
      were determined by applying an immunoassay specific to PSP to pure pancreatic
      juice taken from a total of 52 patients. The patients consisted of 16 controls,
      19 chronic pancreatitis patients (13 noncalcified and 6 calcified), and 17
      probable cases of pancreatitis. The monoclonal antibody PSP antagonist used in
      the study recognizes both forms of the protein, PSP S1 and S2-5, with equal
      effectiveness. No significant reduction of PSP was observed in either calcified
      (mean +/- SEM, 111 +/- 30 micrograms/mg and 24 +/- 3 micrograms/mg protein) or
      noncalcified (305 +/- 133 and 97 +/- 47) chronic pancreatitis patients compared
      with controls (85 +/- 23 and 34 +/- 16). PSP levels did not decrease, at least
      not in the complete forms of the protein found in chronic pancreatitis. PSP
      antibody and assay results indicated that a reduction of PSP S2-5 alone could not
      be ruled out in chronic pancreatitis either.

PMID- 7716139
TI  - Preserved beta-cell density in the endocrine pancreas of young, spontaneously
      diabetic Goto-Kakizaki (GK) rats.
AB  - The Goto-Kakizaki (GK) rat represents a spontaneous animal model of non-insulin
      dependent diabetes mellitus (NIDDM) characterized by impaired glucose-stimulated
      insulin release from the pancreatic beta cells. To study whether an alteration in
      their islet beta-cell numbers occurs in parallel with the impairment of insulin
      secretion in this model, the relative volume density of beta cells was determined
      by means of conventional point sampling in immunostained 4-microns-thick sections
      of the pancreata from 8-week-old GK rats. The pancreata of nondiabetic Wistar
      rats were used as control parenchyma. In the GK pancreata the majority of islets
      was found to have a normal structure; only a few of the islets demonstrated an
      irregular shape (starfish-shaped islets) with fibrosis. The relative volume of
      the total endocrine parenchyma was found to be 2.0 +/- 0.6% (mean +/- SEM) of the
      whole pancreatic parenchyma in GK rats. In the control rats the corresponding
      value was 2.3 +/- 0.5%. The islet beta-cell density was also similar in GK and
      control rat islets, amounting to 75.2 +/- 8.5 and 66.9 +/- 6.6%, respectively.
      Thus, the total relative volume of beta cells was 1.5 +/- 0.5% in GK rats and 1.6
      +/- 0.4% in controls. In conclusion, the density of beta cells is preserved in
      the pancreata of the young, diabetic GK rats, suggesting the absence of a causal
      relationship between the relative pancreatic beta-cell volume and the impaired
      glucose-induced insulin secretion in this NIDDM animal model.

PMID- 7716140
TI  - Carbachol and cholecystokinin enhance accumulation of nicotine in rat pancreatic
      acinar cells.
AB  - Nicotine is a possible risk factor for chronic pancreatitis and pancreatic
      cancer. To study the loci where nicotine might exert its effect, we examined
      interactions between nicotine and rat pancreatic acini. When pancreatic acini
      were incubated with [3H]nicotine, [3H]nicotine levels in pancreatic acini were
      increased in time-and dose-dependent manners, and the t1/2 for dissociation of
      [3H]nicotine was 63.8 min. At 4 degrees C, the association of [3H]nicotine was
      33% of the association at 37 degrees C. Unlabeled nicotine had no significant
      effect on the accumulation of [3H]nicotine. In addition, surface-bound
      [3H]nicotine was not detected when acini were washed in a low-pH solution or when
      they were trypsinized. These results suggest that the accumulation of nicotine
      may be a biological phenomenon and that [3H]nicotine does not bind to surface
      receptors of acinar cells, but accumulates intracellularly. The addition of
      verapamil (0.1 mM) or 12-O-tetradecanoylphorbol-13-acetate (1 microM) had no
      effect on [3H]nicotine association, while 4-bromo-A23187 (2 microM) or EGTA (10
      mM) significantly increased the accumulation of [3H]nicotine. Carbachol and
      cholecystokinin significantly enhanced the accumulation of [3H]nicotine in a dose
      dependent manner. Taken together, the increasing effects of carbachol and
      cholecystokinin on the accumulation of nicotine may explain, at least in part,
      the mechanisms involved in the multiplicative effects of the combination of two
      risk factors, smoking habit and high-fat or high-protein diets, on human
      pancreatic diseases.

PMID- 7716141
TI  - Intracellular degradation of the C-peptide of proinsulin, in a human insulinoma:
      identification of sites of cleavage and evidence for a role for cathepsin B.
AB  - An extract of a neuroendocrine tumor of the human pancreas contained a high
      concentration of insulin and the C-peptide of proinsulin, as determined by
      radioimmunoassay, together with somatostatin, calcitonin, and thymosin beta 4.
      Analysis of the molecular forms of the proinsulin-derived peptides by high
      performance liquid chromatography demonstrated that insulin was stored in the
      tumor as the intact peptide. In contrast, metabolites of C-peptide, representing
      the (1-21), (1-23), (1-25) and (1-29) N-terminal fragments, were isolated from
      the extract in addition to intact C-peptide. Generation of these metabolites
      involves cleavage of Xaa-Leu or Leu-Xaa bonds. Previous immunohistochemical
      studies have identified cathepsin B in secretory granules and lysosomes of human
      insulinoma cells. Synthetic human C-peptide was rapidly cleaved by purified human
      cathepsin B, primarily at the site of leucine residues, to give several
      metabolites, including the (1-25) and (1-23) fragments. The data indicate that
      the C-peptide of proinsulin is selectively metabolized in the neoplastic B cell
      by a mechanism that involves proteolytic cleavages in the C-terminal region of
      the peptide.

PMID- 7716142
TI  - Negative feedback regulation of pancreatic exocrine secretion in guinea pigs.
AB  - We have investigated whether hormonally mediated negative feedback mechanisms
      regulate pancreatic exocrine secretion in guinea pigs. In anesthetized guinea
      pigs prepared with a tube in the proximal duodenum, pyloric ligation, and
      pancreatic duct cannulation with PE-10 tubing, diversion of pancreatic juice for
      as long as 4 h in fasting states failed to increase either pancreatic secretion
      or plasma levels of secretin or cholecystokinin (CCK). In the same animal
      preparation, intraduodenal (ID) infusion of sodium oleate (SO) resulted in
      significant increases in both pancreatic secretin and plasma levels of the two
      hormones that were significantly suppressed by ID infusion of pancreatic juice or
      a combination of trypsin and chymotrypsin. In another group of guinea pigs, this
      significant increase in pancreatic secretion was profoundly suppressed by a
      rabbit antisecretin serum (0.2 ml) or loxiglumide (10 mg.kg-1.h-1). Moreover, a
      combination of the antiserum and loxiglumide completely abolished the pancreatic
      secretion. The effect of atropine, 20 micrograms.kg-1.h-1 i.v., on SO-stimulated
      pancreatic secretion and hormone release was also studied. Atropine completely
      suppressed the pancreatic secretion of volume flow, bicarbonate, and protein
      stimulated by SO, whereas neither one of the two hormone levels was affected by
      intravenous atropine, indicating that atropine blocks the actions of both
      secretin and CCK on the pancreatic exocrine secretion. It is concluded that a
      negative feedback regulation of exocrine pancreatic secretion is operative in the
      intestinal phase of pancreatic secretion in guinea pigs and that this feedback
      mechanism is mediated by both secretin and CCK. Furthermore, in guinea pigs,
      cholinergic tone plays an important modulating role in the mechanism.

PMID- 7716143
TI  - Adrenergic pathways do not mediate peptide YY-induced inhibition of pancreatic
      exocrine secretion.
AB  - The influence of extrapancreatic nerves and intrapancreatic adrenergic activity
      on the inhibition of pancreatic exocrine secretion by peptide YY (PYY) was
      studied in conscious dogs. Chronic pancreatic fistulae were created in five
      mongrel dogs while a second group of five dogs also underwent complete pancreatic
      denervation. After recovery, a continuous infusion of secretin (62 ng/kg/h) and
      cholecystokinin (CCK; 50 ng/kg/h) was administered over 2 h. An infusion of PYY
      (400 pmol/kg/h) was then given randomly, during either the first or second
      experimental hour. The experiments were then replicated after establishing
      adrenergic blockade with continuous background infusions of either phentolamine
      (0.2 mg/kg/h), propranolol (0.5 mg/kg bolus) or a combination of phentolamine and
      propranolol. The secretin/cholecystokinin-induced bicarbonate and protein outputs
      were significantly inhibited by PYY in both the innervated and denervated
      animals. Adrenergic blockade failed to eliminate the inhibitory effects of PYY.
      We conclude that extrapancreatic neural pathways, including adrenergic
      mechanisms, do not mediate the inhibitory effects of PYY. The results suggest
      that PYY inhibits secretin/cholecystokinin-induced pancreatic response by an
      indirect nonadrenergic mechanism.

PMID- 7716144
TI  - Role of bile and trypsin in the release of cholecystokinin in humans.
AB  - The influences of (a) intraluminal bile deficiency due to common bile duct
      obstruction and (b) intraduodenal administration of pooled own bile and bovine
      trypsin on the plasma cholecystokinin (CCK) response to oral fat (Lipomul)
      ingestion were investigated in seven patients with periampullary tumors and 10
      healthy volunteers. Basal and fat-stimulated plasma CCK levels in the patients
      were significantly higher than in the normal controls. Intraduodenal
      administration of pooled own bile at a rate of 100 ml/h significantly suppressed
      both basal and fat-stimulated CCK secretion. Simultaneous administration of
      pooled own bile (100 ml/hr) and bovine trypsin (600 mg/hr) caused further
      significant suppression of fat-stimulated CCK secretion compared with that under
      bile infusion alone. These results indicate that both intraluminal bile and
      trypsin exert a negative feedback effect on the release of CCK in humans.

PMID- 7716145
TI  - Involvement of gene expressions of cholecystokinin and secretin in luminal
      feedback regulation in conscious rats.
AB  - Pancreatic exocrine secretion in conscious rats in regulated by bile and
      pancreatic juice in the proximal intestinal lumen; exclusion of bile and
      pancreatic juice produces release of cholecystokinin (CCK) and pancreatic
      hypersecretion (luminal feedback regulation). In the present study, we examined
      the changes of gene expressions of CCK and secretin, another representative
      gastrointestinal hormone in the intestine, and found that exclusion of bile and
      pancreatic juice significantly enhanced gene expressions of both CCK and
      secretin. These results suggested involvement of both CCK and secretin in luminal
      feedback regulation.

PMID- 7716146
TI  - Spinal epidural abscess after endoscopic treatment for chronic pancreatitis.

PMID- 7716147
TI  - Pancreas divisum: a protection against biliary pancreatitis?

PMID- 7716148
TI  - B-cell lymphoma of ampulla of Vater: observation for six years.

PMID- 7716149
TI  - Insulinoma without hyperinsulinemia.

PMID- 7716150
TI  - Domain insertion.

PMID- 7716151
TI  - GRAFTER: a computational aid for the design of novel proteins.
AB  - The GRAFTER suite of programs provides geometric search and evaluation functions
      that simplify and automate the process of identifying the best scaffolds for a
      particular structural motif. Three application of the GRAFTER suite are
      presented. Potential grafts between lambda repressor and 434 repressor were
      identified that should change the DNA binding specificity of these repressors.
      These results are compared with site-directed mutagenesis experiments that have
      been shown to alter repressor-DNA binding specificity. Next, 26 loops from
      antibody structures were grouped into families of similar structure. Grafts of
      antibody loops onto a pre-existing scaffold are an essential component of
      antibody humanization. Finally, interleukin (IL)-4 was searched as a scaffold
      that might accept the graft of a five residue epitope from human growth hormone
      (hGH). The existence of a crystal structure of the hGH-hGH receptor complex,
      extensive mutagenesis studies of the hGH residues that contribute to the
      energetics of ligand-receptor interactions and the gross structural homology
      between hGH and IL-4 make this an appealing computational target. The approach
      presented here could aid the development of novel enzymes and binding proteins.

PMID- 7716152
TI  - Identification of important functional environs in protein tertiary structures
      from the analysis of residue variation in 3-D: application to cytochromes c and
      carboxypeptidases A and B.
AB  - A simple methodology is described to apply to aligned protein sequence sets for
      which at least one representative 3-D C alpha structure is known. The
      evolutionary variation observed at each residue position in the sequence
      alignment is qualified by taking into account the residue variation that has
      occurred at other positions located within 7 A (according to the probable chain
      fold). This expresses the evolutionary behaviour of any residue position in the
      more appropriate context of its immediate surroundings and distinguishes between
      invariant residues on the basis of the variation of their environment. The
      highest mechanistic significance is attached to conserved residues in conserved
      surroundings, but the quantitative nature of the analysis means that all residue
      vicinities can be ranked and merged according to the degree of conservation that
      they exhibit and the residue positions that comprise them. Therefore, with the
      aid of the chain fold, contour maps can be constructed that show graded foci of
      evolutionary conservation in the underlying superstructure of the protein type,
      and the irregular shapes and extents of large conserved areas. To test the
      methodology, it was applied to cytochromes c and the carboxypeptidases A and B.

PMID- 7716153
TI  - A simple procedure for assigning a sequence motif with an obscure pattern:
      application to the basic/helix-loop-helix motif.
AB  - We have developed a simple method to assign a sequence motif with an obscure
      pattern. Given a multiple sequence alignment for a region of protein that is
      known or strongly believed to have the same secondary and tertiary structures,
      the quantification method by principal component analysis is designed to find the
      regions most likely to have the same structure in a protein outside of the
      original set. The potential of this newly developed method was evaluated with
      reference to the known basic/helix-loop-helix (bHLH) motifs, and its
      characteristics were discussed with four obscure but well-defined motifs and
      compared with the other methods for searching sequence motifs. The method was
      also applied to assign the bHLH motif in Epstein-Barr virus nuclear antigen 1
      (EBNA-1). This application revealed one candidate for the basic/helix 1 region
      and two candidates for the helix 2 region in the bHLH motif, within the region
      from amino acid residues 460 to 600, which is in good agreement with our previous
      experimental studies on the DNA binding region of EBNA-1. The basic/helix-loop
      helix-loop-helix structure thus assigned suggests a function of EBNA-1 which is
      associated with both replication and transcription.

PMID- 7716154
TI  - Ligand-induced domain motion in the activation mechanism of a G-protein-coupled
      receptor.
AB  - Rapidly accumulating information about the structures and functions of
      transmembrane proteins in the class of G-protein-coupled receptors is
      facilitating the exploration of molecular details in the processes of cellular
      signal transduction. We have described recently a 3-D molecular model of the
      transmembrane portion of the 5-HT2A type of receptor of the neurotransmitter
      serotonin (5-hydroxytryptamine; 5-HT), constructed from such convergent empirical
      and theoretical considerations, and have used it for a computational simulation
      of the mechanisms of ligand-induced receptor activation and signal transduction.
      The molecular dynamics (MD) simulation of the interaction between the receptor
      model and ligands of different pharmacological efficacies pointed to a set of
      specific conformational changes propagated from the ligand binding site to a
      distal region of the receptor that is essential for signal transduction. The
      ligand-induced changes were found to correlate well with the known
      pharmacological properties, but it remained unclear how the binding of the small
      5-HT2A receptor agonist molecules in the distal binding pocket could give rise to
      the specific conformational changes in a distant part of the receptor. As the MD
      simulations showed the secondary structure of the helical transmembrane domains
      of the receptor to be well maintained, and the conformational changes to involve
      mainly translations and rotations of the helices in the bundle relative to one
      another, an algorithm was developed to treat the ligand-induced conformational
      changes as rigid domain movements of transmembrane helices.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7716155
TI  - LexA repressor and iron uptake regulator from Escherichia coli: new members of
      the CAP-like DNA binding domain superfamily.
AB  - Comparison of structures can reveal surprising connections between protein
      families and provide new insights into the relationship between sequence,
      structure and function. The solution structure of LexA repressor from Escherichia
      coli reveals an unexpected structural similarity to a widespread class of
      prokaryotic and eukaryotic regulatory proteins, which is typified by catabolite
      gene activator protein (CAP). The use of combined sequence profiles allows the
      identification of two new prokaryotic members of the superfamily: listeriolysin
      regulatory protein (PrfA) and ferric uptake regulatory protein (Fur). LexA, PrfA
      and Fur are the first examples of prokaryotic regulatory proteins in which DNA
      recognition is mediated by a variant of the classical helix-turn-helix motif,
      with an insertion in the turn region.

PMID- 7716156
TI  - Molecular modeling of the interaction of polyproline-based peptides with the Abl
      SH3 domain: rational modification of the interaction.
AB  - A molecular model of the interaction of polyproline-rich peptides with the Abl
      SH3 domain is proposed, based on docking calculations with the DOCK program
      coupled with molecular dynamics simulations. Two distinct binding modes of the
      peptide to the same aromatic-rich region (Tyr10, Phe12, Trp39, Trp50, Tyr55) of
      the domain were obtained. It is proposed that these two models could represent
      different binding modes of proline-rich peptides to Src homology region 3
      domains. Several peptide mutants were designed to determine whether the two
      orientations were possible. Analysis of the Kd values and fluorescence emission
      of these peptides indicate that one of the orientations is more plausible and
      that residues at position 4 of the peptide interact with the RT loop, being
      important in modulating the peptide affinity for the Abl-SH3 domain.

PMID- 7716157
TI  - The stability and unfolding of an IgG binding protein based upon the B domain of
      protein A from Staphylococcus aureus probed by tryptophan substitution and
      fluorescence spectroscopy.
AB  - The stability and unfolding of an immunoglobulin (Ig) G binding protein based
      upon the B domain of protein A (SpAB) from Staphylococcus aureus were studied by
      substituting tryptophan residues at strategic locations within each of the three
      alpha-helical regions (alpha 1-alpha 3) of the domain. The role of the C-terminal
      helix, alpha 3, was investigated by generating two protein constructs, one
      corresponding to the complete SpAB, the other lacking a part of alpha 3; the Trp
      substitutions were made in both one- and two-domain versions of each of these
      constructs. The fluorescence properties of each of the single-tryptophan mutants
      were studied in the native state and as a function of guanidine-HCl-mediated
      unfolding, and their IgG binding activities were determined by a competitive
      enzyme-linked immunosorbent assay. The free energies of folding and of binding to
      IgG for each mutant were compared with those for the native domains. The effect
      of each substitution upon the overall structure and upon the IgG binding
      interface was modelled by molecular graphics and energy minimization. These
      studies indicate that (i) alpha 3 contributes to the overall stability of the
      domain and to the formation of the IgG binding site in alpha 1 and alpha 2, and
      (ii) alpha 1 unfolds first, followed by alpha 2 and alpha 3 together.

PMID- 7716158
TI  - The effect of ion pairs on the thermal stability of D-glyceraldehyde 3-phosphate
      dehydrogenase from the hyperthermophilic bacterium Thermotoga maritima.
AB  - D-Glyceraldehyde 3-phosphate dehydrogenase from Thermotoga maritima (TmGAPDH) is
      intrinsically thermostable, exhibiting a thermal transition beyond 105 degrees C.
      Neither the amino-acid composition nor homology modelling, based on sequence
      alignment and known 3-D structures of the enzyme from meso- and thermophiles,
      provide an explanation of the anomalous stability. Recent X-ray data suggest that
      an increased number of ion pairs is involved. To prove this hypothesis, a number
      of charged residues contributing to ion pairs in TmGAPDH, but absent in the
      moderately thermophilic enzyme were altered. Elimination of peripheral ion pairs
      (E103-K104, E261-R266) was found to be ineffective. Altering a central charge
      cluster (R10-D47, E314, D*186) led to a drastic decrease in coenzyme binding. As
      a consequence, guanidine-dependent deactivation is shifted to significantly lower
      guanidinium chloride (GdmCl) concentrations without altering the
      denaturation/dissociation profile of the wild type enzyme. Mutants in the S loop
      (R195D, R195D-D181K) lead to a biphasic profile in the GdmCl-dependent
      denaturation transition and significant destabilization; at room temperature no
      subunit dissociation could be observed.

PMID- 7716159
TI  - Protein engineering of the relative specificity of glucoamylase from Aspergillus
      awamori based on sequence similarities between starch-degrading enzymes.
AB  - Aspergillus glucoamylase catalyzes hydrolysis of D-glucose from non-reducing ends
      of starch with an approximately 300-fold (kcat/Km) preference for the alpha-1,4-
      over the alpha-1,6-glucosidic linkage determined using the substrates maltose and
      isomaltose. It is postulated that as most amylolytic enzymes act on either the
      alpha-1,4- or alpha-1,6-linkages, sequence comparison between active-site regions
      should enable the correlation of the substrate bond specificity with particular
      residues at key positions. Therefore, the already high bond-type selectivity in
      Aspergillus glucoamylase could theoretically be augmented further by three single
      mutations, Ser119-->Tyr, Gly183-->Lys and Ser184-->His, in two separate active
      site regions. These mutants all had slight increases in activity as compared with
      the wild-type enzyme towards the alpha-1,4-linked maltose; this was due to lower
      Km values as well as small decreases in activity towards isomaltose. This latter
      decrease in activity was a result of higher Km values and a decrease in kcat for
      the Ser184-->His mutant. As a consequence, the selectivity of the three
      glucoamylase mutants for alpha-1,4- over alpha-1,6-linked disaccharides is
      enhanced 2.3- to 3.5-fold. In addition, the introduction of a cationic side chain
      in Gly183-->Lys and Ser184-->His glucoamylase, broadens the optimal pH range for
      activity towards acidic as well as alkaline conditions.

PMID- 7716160
TI  - Structure-function validation of high lysine analogs of alpha-hordothionin
      designed by protein modeling.
AB  - Cereal grains and legume seeds, which are key protein sources for the vegetarian
      diet, are generally deficient in essential amino acids. Maize, in particular, is
      deficient in lysine. The inherent lack of lysine-rich proteins in maize has
      necessitated the search for heterologous proteins enriched in this amino acid,
      the isolation of the corresponding gene and its ultimate introduction into maize
      through plant transformation techniques. However, a rate-limiting step to this
      strategy has been the availability of plant-derived lysine-rich proteins. An
      appealing solution to the problem is to artificially increase the lysine content
      of a given protein by mutating appropriate residues to lysine. Here, we expound
      this strategy, starting with the protein alpha-hordothionin that is derived from
      barley seeds and consists of five lysine residues in a total of 45 amino acids
      (11% lysine). To facilitate rational substitutions, the 3-D structure of the
      protein has been determined by homology modeling with crambin. Based on this
      model, we have identified surface residues amenable to substitution with lysine.
      Furthermore, the acceptability of the mutations has been validated through the
      synthesis and characterization of the derivatives. To this end, our approach has
      permitted the creation of a modified alpha-hordothionin protein that has a lysine
      content of approximately 27% and retains the antifungal activity of the wild-type
      protein.

PMID- 7716161
TI  - A single amino acid substitution can restore the solubility of aggregated colicin
      A mutants in Escherichia coli.
AB  - Mutants of colicin A have been prepared in which the three tryptophan residues
      (Trp86, Trp130 and Trp140), localized in the C-terminal domain of the soluble
      wild-type protein, have been substituted by phenylalanine. The Trp140Phe single
      mutation had the effect of decreasing the percentage of protein that is expressed
      as insoluble aggregates. The created hydrophobic cavity decreased the stability
      of the protein during its folding, resulting in partial aggregation in the
      cytoplasm of the Escherichia coli-producing cells. Aggregation was increased when
      Trp140 was substituted by Lys, Leu or Cys, or if the Trp140 mutation was combined
      with the Trp86Phe and/or Trp130Phe mutations. A single mutation, Lys113Phe,
      however, was able to restore the solubility of the aggregated mutants in vivo.
      Detailed analysis of the 3-D structure of the C-terminal domain of colicin A
      suggests that filling of the hydrophobic cavity is responsible for this effect.

PMID- 7716162
TI  - Efficient generation of a reshaped human mAb specific for the alpha toxin of
      Clostridium perfringens.
AB  - We have used the technique of antibody reshaping to produce a humanized antibody
      specific for the alpha toxin of Clostridium perfringens. The starting antibody
      was from a mouse hybridoma from which variable (V) region nucleotide sequences
      were determined. The complementarity-determining regions (CDRs) from these V
      regions were then inserted into human heavy and light chain V region genes with
      human constant region gene fragments subsequently added. The insertion of CDRs
      alone into human frameworks did not produce a functional reshaped antibody and
      modifications to the V region framework were required. With minor framework
      modifications, the affinity of the original murine mAb was restored and even
      exceeded. Where affinity was increased, an altered binding profile to overlapping
      peptides was observed. Computer modelling of the reshaped heavy chain V regions
      suggested that amino acids adjacent to CDRs can either contribute to, or distort,
      CDR loop conformation and must be adjusted to achieve high binding affinity.

PMID- 7716163
TI  - Cloning, expression and characterization of the Fv fragments of the anti
      carbohydrate mAbs B1 and B5 as single-chain immunotoxins.
AB  - The mAbs B1 (IgG1 kappa) and B5 (IgM kappa) recognize carbohydrate epitopes on
      human carcinoma cells. The Fv regions of these antibodies were separately cloned
      from hybridoma RNA using reverse transcription and PCR with oligonucleotide
      primers designed according to the amino acid sequences of the N-termini. The Fv
      regions also provide sequences for translation initiation in Escherichia coli
      (Fr1 oligos) and sequences of the constant region of the heavy and light domains
      (CH1 or C-kappa oligos). Following the determination of the DNA sequence of the
      Fvs, primers were designed according to the 3' ends of the VH and VL domains.
      These also provided for a peptide linker at the C-terminus of the VH and a short
      connector at the C-terminus of the VL (Fr4 oligos). The VH and VL were then each
      PCR-amplified using their corresponding Fr1 and phosphorylated Fr4 oligos. The
      resulting PCR products were annealed as 'mutagenic primers' to a uracil
      containing single-stranded template obtained from an expression plasmid encoding
      a single-chain immunotoxin in which the B3 single-chain Fv is fused to a
      truncated form of Pseudomonas exotoxin (PE). Thus, the B1 and B5 variable domains
      replaced their corresponding B3 domains in the expression plasmid by 'variable
      domain shuffling' without subcloning. The resulting B1(Fv)-PE38 and B5(Fv)-PE38
      were expressed in E. coli and purified to near homogeneity. Both show specific
      cytotoxicities to human carcinoma cell lines, but B1(Fv)-PE38 is much more
      active, reflecting its higher affinity to the target cells.

PMID- 7716164
TI  - Predicted secondary and supersecondary structure for the serine-threonine
      specific protein phosphatase family.
AB  - A bona fide consensus prediction for the secondary and supersecondary structure
      of the serine-threonine specific protein phosphatases is presented. The
      prediction includes assignments of active site segments, an internal helix, and a
      region of possible 3(10) helical structure. An experimental structure for a
      member of this family of proteins should appear shortly, allowing this prediction
      to be evaluated.

PMID- 7716165
TI  - Thermodynamic genetics of the folding of the B1 immunoglobulin-binding domain
      from streptococcal protein G.
AB  - A method has been developed to select proteins that are thermodynamically
      destabilized yet still folded and functional. The DNA encoding the B1 IgG-binding
      domain from Group G Streptococcus (Strp G) has been fused to gene III of
      bacteriophage M13. The resulting fusion protein is displayed on the surface of
      the phage thus enabling the phage to bind to IgG molecules. In addition, these
      phage exhibit a small plaque phenotype that is reversed by mutations that
      destabilize the Strp G domain. By selecting phage with large plaque morphology
      that retain their IgG-binding function, it is possible to identify mutants that
      are folded but destabilized compared with wild-type Strp G. Such mutants can be
      divided into three general categories: 1) those that disrupt packing of
      hydrophobic side chains in the protein interior; 2) those that destabilize
      secondary structure; and 3) those that alter specific hydrogen bonds involving
      amino acid side chains. A number of the mutants have been physically
      characterized by circular dichroism and nuclear magnetic resonance and have been
      shown to have structures similar to wild-type Strp G but stabilities that were
      decreased by 2-5 kcal/mol.

PMID- 7716166
TI  - Model assembly study of the ligand binding by p-hydroxybenzoate hydroxylase:
      correlation between the calculated binding energies and the experimental
      dissociation constants.
AB  - The energies of binding of seven ligands by p-hydroxybenzoate hydroxylase (PHBH)
      were calculated theoretically. Direct enzyme-ligand interaction energies were
      calculated using the ab initio quantum mechanical model assembly of the active
      site at the 3-21G level. Solvation energies of the ligands needed in the
      evaluation of the binding energies were calculated with the semiempirical AM1-SM2
      method and the long-range electrostatic interaction energies between the ligands
      and the protein matrix classically using the static charge distributions of the
      ligands and the protein. Energies for proton-transfer between the ligands' OH or
      SH substituent at position 4 and the active-site tyrosine within the ab initio
      model assemblies were calculated and compared to the corresponding pKas in
      aqueous solution. Excluding 3,4-dihydroxybenzoate, the natural product of PHBH, a
      linear relationship between the calculated binding energies and the experimental
      binding free energies was found with a correlation coefficient of 0.90.
      Contributions of the direct enzyme-ligand interaction energies, solvation
      energies and the long-range electrostatic interaction energies to the calculated
      binding energies were analyzed. The proton-transfer energies of the ligands with
      substituents ortho to the ionized OH were found to be perturbed less in the model
      calculations than the energies of their meta isomers as deduced from the
      corresponding pKas.

PMID- 7716167
TI  - Elusive affinities.
AB  - The affinity of two molecules for each other and its temperature dependence are
      determined by the change in enthalpy, free enthalpy, entropy, and heat capacity
      upon dissociation. As we know the forces that stabilize protein-protein or
      protein-DNA association and the three-dimensional structures of the complex, we
      can in principle derive values for each one of these parameters. The calculation
      is done first in gas phase by molecular mechanics, then in solution with the help
      of hydration parameters calibrated on small molecules. However, estimates of
      enthalpy and entropy changes in gas phase have excessively large error bars even
      under the approximation that the components of the complex associate as rigid
      bodies. No reliable result can be expected at the end. The fit to experimental
      values derived from binding and calorimetric measurements is poor, except for the
      dissociation heat capacity. This parameter can be attributed mostly to the
      hydration step and it correlates with the size of the interface. Many protein
      protein complexes have interface areas in the range 1200-2000 A2 and only small
      conformation changes, so the rigid body approximation applies. It is less
      generally valid in protein-DNA complexes, which have interfaces covering 2200
      3100 A2, large dissociation heat capacities, and affect both the conformation and
      the dynamics of their components.

PMID- 7716168
TI  - Molecular dynamics simulations of alcohol dehydrogenase with a four- or five
      coordinate catalytic zinc ion.
AB  - A detailed parameterization is presented of a zinc ion with one histidine and two
      cysteinate ligands, together with one or two water, hydroxide, aldehyde, alcohol,
      or alkoxide ligands. The parameterization is tailored for the active site of
      alcohol dehydrogenase and is obtained entirely from quantum chemical
      computations. The force-field reproduces excellently the geometry of quantum
      chemically optimized zinc complexes as well as the crystallographic geometry of
      the active site of alcohol dehydrogenase and small organic structures. The
      parameterization is used in molecular dynamics simulations and molecular
      mechanical energy minimizations of alcohol dehydrogenase with a four- or five
      coordinate catalytic zinc ion. The active-site zinc ion seems to prefer four
      coordination over five-coordination by at least 36 kJ/mol. The only stable
      binding site of a fifth ligand at the active-site zinc ion is opposite to the
      normal substrate site, in a narrow cavity behind the zinc ion. Only molecules of
      the size of water or smaller may occupy this site. There are large fluctuations
      in the geometry of the zinc coordination sphere. A four-coordinate water molecule
      alternates frequently (every 7 ps) between the substrate site and the fifth
      binding site and even two five-coordinate water molecules may interchange
      ligation sites without prior dissociation. Ligand exchange at the zinc ion
      probably proceeds by a dissociative mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716169
TI  - Modulation of DNA-binding specificity within the nuclear receptor family by
      substitutions at a single amino acid position.
AB  - Regulation of gene expression involves a large number of transcription factors
      with unique DNA-binding properties. Many transcription factors belong to families
      of related proteins that bind to similar but distinct sequences. In this study we
      have analyzed how amino acid substitutions at a single position in the DNA
      binding domain modulate the DNA-binding specificity within the nuclear receptor
      family of transcription factors. All possible amino acids were introduced at the
      first position in the DNA recognition helix, and the specificities of the mutants
      were analyzed using response elements containing all combinations of bases at two
      variable base pair positions. All mutant proteins were functional in DNA binding,
      and could be divided into classes of mutants with different response element
      specificities. By combining functional data with analysis of the structural
      effects of the mutations by molecular modeling, we could identify both
      prohibitive steric interactions as well as positive interactions, such as
      hydrogen bonds, that function as important determinants for specificity. Only the
      residues found naturally in the glucocorticoid and estrogen receptors, glycine
      and glutamate, produce unique binding specificities. The specificities of the
      other mutants overlap with each other somewhat but the substitutions clearly have
      potential to contribute to diversity within the nuclear receptor family.

PMID- 7716170
TI  - Crystallization and preliminary structural studies of the ncd motor domain.
AB  - The motor domain of the kinesin homolog ncd has been crystallized in the presence
      of MgATP by the vapor diffusion method using polyethylene glycol as the
      precipitant. The crystals belong to the orthorhombic space group I222 with unit
      cell dimensions a = 127.1 A, b = 122.3 A, c = 68.0 A, and there is one ncd
      molecule per asymmetric unit. The crystals diffract X-ray to at least 2.3 A and
      are appropriate for high-resolution structure determination.

PMID- 7716171
TI  - Crystallization and preliminary crystallographic study of human CksHs1: a cell
      cycle regulatory protein.
AB  - The cell cycle regulatory protein CksHs1 has been crystallized in a form suitable
      for X-ray studies. CksHs1 crystals were grown in the presence of vanadate, a
      phosphatase inhibitor, but were also obtained with phosphate or tungstate as a
      cofactor. They belong to the hexagonal space group P6(1)22 with unit cell
      dimensions: a = b = 94 A, c = 131.6 A, and gamma = 120 degrees. The crystals
      grown in the presence of vanadate diffract X-rays to at least 2.8 A. Molecular
      replacement results from the homologous human CksHs2 structure reveal that a
      dimer forms the crystal habit, giving the unusual Vm value of 4.4 A3/Da or a
      solvent content of 72%.

PMID- 7716172
TI  - Crystals of an antibody Fv fragment against an integral membrane protein
      diffracting to 1.28 A resolution.
AB  - The Fv fragment of a monoclonal antibody, 7E2 (IgG1, kappa, murine), which is
      directed against the integral membrane protein cytochrome c oxidase (EC 1.9.3.1)
      from Paracoccus denitrificans, was cloned and produced in Escherichia coli.
      Crystals suitable for high-resolution X-ray analysis were obtained by
      microdialysis under low salt conditions. The crystals belong to the orthorhombic
      space group P2(1)2(1)2(1) with unit cell dimensions of a = 51.51 A, b = 56.15 A,
      c = 99.86 A (1 A = 0.1 nm) and contain one Fv fragment per asymmetric unit. Using
      synchrotron radiation diffraction data were collected up to 1.28 A resolution.
      This high resolution is very unusual for a heterodimeric protein. The crystals
      should open the way for refining not only the atomic positions, but also for
      obtaining information about internal dynamics.

PMID- 7716173
TI  - Preliminary X-ray diffraction analysis of crystals of turnip yellow mosaic virus
      (TYMV).
AB  - Turnip yellow mosaic virus (TYMV) was purified from Chinese cabbage and
      crystallized in a form that permits high resolution structural analysis using X
      ray diffraction. The crystals have a hexagonal bipyramidal morphology and often
      achieve dimensions of 1.0 x 1.0 x 0.5 mm. The crystals appear to be of hexagonal
      space group P6(2)22 with a=b=525 A, c=315 A, but we cannot strictly rule out the
      possibility that the space group is P622. They appear different than any crystals
      of TYMV previously reported. There are three T = 3 virus particles in the unit
      cell, which implies that one quarter of the particle, or 45 protein subunits,
      comprises the asymmetric unit of the crystal. Native data have been collected
      using synchrotron radiation to a resolution of 3.2 A.

PMID- 7716174
TI  - Inhibitory action of hydrogen peroxide on a high-resistance epithelium.
AB  - The present study describes the action of H2O2 on active transporting epithelium,
      and the partial blockade of this action by antioxidants. The addition of
      increasing concentrations of H2O2 (0.80; 8.0 and 24.0 mmol/l) to the mucosal
      surface of isolated toad skin causes an irreversible and dose-dependent
      inhibition of the short circuit current (SCC) and potential difference (PD).
      Quantitative determination of the parameters of the electrical equivalent circuit
      of the skin, by means of Isaacson's amiloride test, shows that the most affected
      parameters were the SCC, PD and shunt conductance. When the skins were
      preincubated with mannitol and vitamin E, the inhibition elicited by H2O2 was
      partially blocked; on the other hand, when the skins were preincubated with
      superoxide dismutase or allopurinol, this inhibition remains unchanged. The
      thiobarbituric acid method was used as an indirect quantification of lipid
      peroxidation. The inhibitory action of H2O2 in terms of the equivalent electrical
      circuit and the parallel production of lipid peroxidation points to free-radical
      formation. Furthermore, the significant blockade of this action by some enzymatic
      antioxidants is in agreement with this hypothesis.

PMID- 7716175
TI  - The role of the mucosa in the in vitro changes in guinea pig bladder function
      which occur after sensitization with ovalbumin.
AB  - Bladder strips from sensitized guinea pigs respond to ovalbumin challenge with a
      contraction accompanied by release of histamine, prostaglandin, and leukotriene.
      Histamine and prostaglandin release occurs preferentially from the bladder
      mucosa, while leukotrienes are released by the smooth muscle. This study
      investigated the effects of removal of the bladder mucosa on contractile
      responses of strips from control and sensitized guinea pigs to electrical
      stimulation and to contractile agonists. Removal of the mucosa potentiated the
      contractile response to electrical stimulation at low voltages and pulse
      durations. The presence of ovalbumin had no effects on the response to electrical
      stimulation. Removal of the mucosa had no effect on the contractile responses of
      bladder strips to bethanechol, histamine, KCl, or ovalbumin, although after
      correction for the decreased strip mass after mucosa removal there was a tendency
      for the responses to increase. We conclude that the responsiveness of bladder
      strips from sensitized guinea pigs to ovalbumin challenge results primarily from
      effects which occur within the smooth muscle.

PMID- 7716177
TI  - Involvement of spontaneous nitric oxide production in the diabetogenic action of
      streptozotocin.
AB  - The exact mechanism by which streptozotocin (STZ) destroys pancreatic beta-cells
      has not been determined. Recently, nitric oxide was identified as a potent islet
      toxic compound. However, nitric oxide production by STZ has not been proved yet.
      In the present studies, we determined whether STZ spontaneously produces nitrite,
      measured by a spectrophotometric technique based on the Griess reaction. STZ,
      dissolved in the pH 4.0 citrate buffer, produced significantly more nitrite than
      that dissolved in pH 7.4. After incubation at 37 degrees C for 120 min, nitrite
      concentrations were significantly decreased only in STZ dissolved in the pH 7.4
      citrate buffer. Following 120 min incubation at 37 degrees C, STZ dissolved at pH
      7.4 failed to cause significant islet damage in rats previously deprived of food
      for 18 h. The present studies demonstrated that STZ may spontaneously produce
      nitrite in vitro. Nitric oxide production may, at least in part, be responsible
      for the STZ-induced damage of pancreatic beta-cells of the rodents.

PMID- 7716176
TI  - Distribution and retention of nicotine and its metabolite, cotinine, in the rat
      as a function of time.
AB  - Nicotine is oxidized to its major metabolite, cotinine, which has a long
      biological half-life (19-24 h). The plasma concentration of cotinine has been
      used as an index of tobacco smoke exposure. Cotinine possibly increases the
      turnover rate of platelet-activating factor (PAF) because it is a potent
      activator of PAF hydrolase, and it may play a significant role in tobacco-induced
      arterial thrombosis. Therefore, we studied the distribution and retention of
      nicotine as it was metabolized to cotinine in the rat. Nicotine (1 mg/kg, 5
      microCi/kg) was administered into the femoral vein of male Sprague-Dawley rats
      under nembutal anesthesia. At different times (5-60 min) after nicotine
      administration, nicotine and its metabolite, cotinine, were determined by HPLC in
      plasma, liver, kidney, heart and brain. Within 5-10 min after administration,
      nicotine concentrations reached peak values in plasma (2,160 pmol/ml) and the
      organs analyzed. The plasma level of nicotine decreased by 50% within 20 min
      (half-time) after its intravenous administration. The half-time of nicotine in
      the brain was about 50 min. The half-times of nicotine for the other organs were
      about 20-25 min. The major metabolite, cotinine, accumulated in plasma, and by
      about 30 min the concentrations of nicotine and cotinine in plasma were about
      equal (890-1,000 pmol/ml). While cotinine accumulated in plasma, nicotine was
      eliminated by the kidney. While the nicotine concentrations decreased with time
      in all organs, cotinine concentrations remained constant. These observations
      indicate that nicotine is renally eliminated or metabolized to cotinine while
      cotinine exhibits a long retention time and accumulates in plasma.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7716178
TI  - Mechanism of sodium nitroprusside-mediated inhibition of aromatic amino acid
      decarboxylase activity.
AB  - The effects of sodium nitroprusside (SNP) on dopamine synthesis in a porcine
      renal epithelial cell line (LLC-PK1) were evaluated. Subsequent studies examined
      the actions of the degradation products of SNP (cyanide, ferrous ion and nitric
      oxide) on aromatic amino acid decarboxylase (AAAD) activity in tissue
      supernatants from LLC-PK1 cells and rat renal cortex. SNP (10-500 mumol/l)
      significantly inhibited dopamine production in LLC-PK1 cells in a dose-related
      manner. The activation of guanylate cyclase by nitric oxide was not found to be
      the mechanism whereby SNP inhibited dopamine synthesis in LLC-PK1 nor did the
      antioxidant glutathione attenuate the actions of SNP. Ferrous sulfate (0.5
      mmol/l) and SNP (0.5 mmol/l) were found to inhibit dopamine synthesis in LLC-PK1
      cells and to directly inhibit cytosolic AAAD activity from LLC-PK1 cells. A
      series of studies were conducted using AAAD from rat renal cortex and confirmed
      that SNP could directly inhibit the conversion of L-dopa to dopamine by AAAD.
      Furthermore, potassium ferricyanide (1 mmol/l) and potassium cyanide (1 mmol/l)
      could produce greater than 80% reductions in AAAD activity. Iron (0.5-1 mmol/l)
      was found to increase rat kidney AAAD activity. Kinetic analysis revealed that
      potassium cyanide was a potent (Ki = 40-50 mumol/l) noncompetitive/mixed
      noncompetitive inhibitor of AAAD. SNP was also found to be a noncompetitive
      inhibitor of AAAD with a Ki of approximately 300-500 mumol/l. In contrast,
      ferrous sulfate (0.5 mmol/l) was a competitive inhibitor (Ki = approximately 650
      mumol/l) that actually increased the Vmax of AAAD. The results of these studies
      support that cyanide released from SNP can potently inhibit AAAD, although SNP
      has somewhat more complex interactions with AAAD due to the presence of ferrous
      ion.

PMID- 7716179
TI  - Dose-related cardioprotection by ifetroban in relation to inhibition of
      thrombosis and ex vivo platelet function.
AB  - The dose-related cardioprotective efficacy of the thromboxane A2/prostaglandin
      endoperoxide (TP) receptor antagonist, ifetroban (BMS-180291), was investigated
      in an anesthetized ferret model of myocardial ischemia (90 min) followed by
      reperfusion (5 h). Treatment was begun at either the 75th minute of ischemia or 5
      min after initiating reperfusion. The magnitude of TP receptor blockade was
      evaluated by ex vivo platelet function. Additional experiments in ferrets tested
      the antithrombotic potency of ifetroban as an inhibitor of thrombotic cyclic flow
      reduction (CFR) in the stenosed abdominal aorta (Folts model). Continuous
      ifetroban infusions of 0.03, 0.1 and 0.3 mg/kg/h reduced myocardial infarct size
      from 22% of the left ventricle in vehicle-control ferrets to 20, 12 and 9%,
      respectively. These represented reductions in infarct size of 8, 43 and 56%.
      Delaying initiation of treatment with high-dose ifetroban until 5 min into
      reperfusion also significantly reduced infarct size by 45%. High-dose ifetroban
      treatment did not prevent neutrophil (PMNL) accumulation measured as tissue
      myeloperoxidase activity in infarcted tissue. At the end of the 5-hour
      reperfusion period, the low, medium and high doses produced 90, 98 and 98%
      blockade of platelet TP receptors, respectively, measured as inhibition of ex
      vivo platelet shape change responses to U-46,619. Ifetroban inhibited thrombotic
      CFR at a threshold dose of 0.03 +/- 0.004 mg/kg, which antagonized 92% of ferret
      platelet TP receptors. Thus, ifetroban exhibited cardioprotective and
      antithrombotic activities and was effective at doses producing > 90% TP receptor
      blockade. Cardioprotective activity was not associated with any reductions of
      PMNL accumulation in infarcted tissue and was demonstrable even when treatment
      was delayed until 5 min after initiation of reperfusion.

PMID- 7716180
TI  - Astroglial neurotrophic and neurite-promoting factors.
AB  - Astroglial cells express neurotrophic and/or neurite growth-promoting factors,
      including (a) peptide growth factors (e.g. nerve growth factors, ciliary
      neuronotrophic factor, fibroblast growth factor), (b) neurotransmitters (such as
      glutamate, neuropeptide Y), (c) cell adhesion molecules (e.g. N-CAM) and (d)
      extracellular matrix proteins (including laminin, fibronectin and proteoglycans).
      Expression of these molecules is regulated during development and/or after CNS
      lesions. Some of the astroglial peptide growth factors, including nerve growth
      factor, basic fibroblast growth factor and ciliary neuronotrophic factor, have
      been shown to exert protective or even regenerative effects on neurons following
      traumatic, chemical or ischemic lesions. These observations illustrate the
      enormous therapeutic potential of astroglia-derived neurotrophic molecules.

PMID- 7716181
TI  - Novel applications of misoprostol.
AB  - Misoprostol, a prostaglandin E1 analogue, is currently licensed primarily to
      prevent non-steroidal anti-inflammatory drug-associated gastric and duodenal
      ulcers. Further work shows the drug prevents triggering of a variety of
      inflammatory processes and the release of tissue damaging cytokines and other
      mediators involved in conditions as diverse as asthma and osteoarthritis. Thus,
      misoprostol may help restore or maintain normal homeostasis and limit inhibitory
      effects on essential repair processes. Therapeutic implications include
      limitation of renal, hepatic, gastrointestinal and radiation-induced tissue
      injury and prevention of inflammatory and allergic disorders, including the late
      phase inflammatory response in asthma, either alone or in synergy with other
      agents.

PMID- 7716182
TI  - Treatment and prevention of chronic viral hepatitis.
AB  - Chronic viral hepatitis caused by hepatitis B, C or D may lead to cirrhosis,
      hepatocellular failure and hepatocellular carcinoma. The morbidity of these
      diseases has necessitated a prolonged search for effective therapy. Interferon
      alpha has been studied widely, and remains the mainstay of treatment. Therapy for
      hepatitis B has now become possible with the demonstration that alpha-interferons
      inhibit hepatitis B virus (HBV) replication and that prolonged therapy can lead
      to a remission in disease. A number of other cytokines, including thymosin, are
      being evaluated. Currently used nucleoside analogues and anti-retroviral
      therapies used in human immunodeficiency virus infection have not proven useful
      in chronic hepatitis B. There are a number of new experimental nucleoside
      analogues with activity against HBV. Unfortunately, fialuridine has been
      associated with severe mitochondrial damage and hepatotoxicity. Other
      stereoisomers may be more active and less toxic, but the potential danger of
      these drugs indicates that large scale clinical trials should proceed cautiously.
      Experimental test systems for the preliminary investigation of antiviral
      compounds in hepatitis B and C will be required. Antisense
      oligodeoxyribonucleotides may inhibit the expression of the HBV genes. The
      natural history of hepatitis C is uncertain. Therapeutic trials of interferon
      alpha indicated that a proportion of patients may respond to treatment with this
      agent. There is most information about 3 mU t.i.w. administered for 6 months. It
      is not yet clear whether this dose is optimal. Multivariate analysis of several
      pretreatment parameters indicate that patients without cirrhosis are more
      responsive to interferon. The influence of genotypes of hepatitis C is the
      subject of considerable interest at present. Patients with diverse circulating
      quasispecies may be less responsive to therapy than those with a single major
      species. Improved responses have been observed in patients with lower levels of
      circulating hepatitis C virus RNA.

PMID- 7716183
TI  - Mechanisms of hypoxic cerebral vasodilatation.
AB  - Hypoxia activates multiple mechanisms that influence cerebrovascular tone.
      Through actions on non-vascular cerebral elements, hypoxia stimulates the
      production of a wide variety of vasodilator metabolites, the most important of
      which are potassium and hydrogen ions, prostaglandins and adenosine. Hypoxia also
      promotes the neuronal release of excitatory amino acids, which stimulates overall
      cerebral metabolism and further enhances the release of vasodilator metabolites.
      Altogether, the combined action of these metabolites, many of which remain
      unidentified, account for approximately half the vasodilatation associated with
      moderate to severe hypoxia. The remaining vasodilatation is attributable to
      direct effects of hypoxia on cerebral arteries. One component of the direct
      vascular effects of hypoxia involves the endothelium, which can release at least
      three different vasodilating factors (prostacyclin, nitric oxide and
      hyperpolarizing factor) and two different contracting factors (indomethacin
      sensitive and indomethacin-resistant) in response to hypoxia. In cerebral
      arteries, the net contribution of endothelial factors to hypoxic vasodilatation
      appears to be modest, although the exact profile of factors released by hypoxia
      appears to depend on both species and artery type. Within the vascular smooth
      muscle cells of cerebral arteries, hypoxia activates membrane ATP-sensitive
      potassium channels, resulting in hyperpolarization of the smooth muscle membrane
      and reduced calcium permeability. In addition, hypoxia also appears capable of
      retarding flux through the inositol phosphate cascade and reducing the second
      messenger stimulus for release of intracellular calcium. Both of these latter
      influences, which may be caused by hypoxic changes in intracellular ATP, ADP and
      hydrogen ion concentrations, act to lower the free cytosolic calcium
      concentration available to support contraction. Hypoxia also appears to reduce
      the calcium sensitivity of contractile proteins. Combined, these mechanisms exert
      a powerful and multifaceted inhibitory influence on cerebrovascular tone.

PMID- 7716184
TI  - The regulation of nerve growth factor synthesis and delivery to peripheral
      neurons.
AB  - Recent experiments have provided new insights into the way in which the synthesis
      of nerve growth factor (NGF) is regulated. In particular, a variety of agents
      have been found to influence the cellular concentration of mRNANGF and NGF both
      in vitro and in vivo. However, no clear mechanism has been found to indicate the
      existence of a feedback regulation of NGF synthesis by effector tissue
      innervation. We have argued in this review that some form of feedback control is
      likely to exist between the innervation and the cells producing the factor. One
      such possibility, the regulation of the availability of NGF by control of its
      secretion, is discussed.

PMID- 7716185
TI  - Native speakers of Spanish show rate-dependent processing of English stop
      consonants.
AB  - English monolinguals and native Spanish speakers of English used a 9-point scale
      to rate syllable-initial stops for goodness as realizations of the English /p/
      category. Voice onset time (VOT) was varied in a set of short-duration ('fast
      rate') consonant-vowel (CV) stimuli, and in a set of longer-duration ('slow
      rate') CV stimuli. The VOT values ranged from values typical for English /b/ to
      values which exceeded those typical for English /p/. Results for the native
      English (NE) subjects replicated those obtained previously using the same two
      continua. Goodness ratings systematically increased, then decreased as VOT values
      extended beyond the range typical for English /p/. The NE subjects gave their
      highest ratings to stimuli with VOT values of about 50 ms. For stops with longer
      VOT values, their ratings were higher for stimuli in the slow-rate than fast-rate
      continuum. The native Spanish (NS) subjects were assigned to two subgroups based
      on degree of foreign accent in their pronunciation of English sentences. Both
      proficient and nonproficient NS subjects gave their highest ratings to stimuli
      with much the same VOT values as the NE subjects, even though /p/ is realized
      with short-lag VOT in Spanish. The nonproficient, but not the proficient NS
      subjects showed significantly smaller rate effects on goodness ratings than did
      the NE subjects. However, the subjects in both NS groups gave significantly
      higher ratings to stimuli with short-lag VOT values than did the NE subjects. The
      results are discussed in terms of the hypothesis that adult learners of a second
      language may establish new perceptual phonetic categories for phonetic segments
      not found in the native language.

PMID- 7716186
TI  - Solar ultraviolet radiation and the risk of infectious disease: summary of a
      workshop.

PMID- 7716187
TI  - Reactivity of singlet oxygen toward large peptides.
AB  - The reactions of singlet oxygen, 1O2, with amino acids and their derivatives have
      been studied previously. It was found that only five amino acid residues interact
      readily with 1O2. Here we describe its reactions with the large peptides
      melittin, neuropeptide Y (NPY) and insulin in their native and in their denatured
      forms. The singlet oxygen quenching by a polypeptide was compared with that of a
      solution at the same concentration as those of its constituent amino acids, which
      are known to react efficiently with 1O2. It was found that the quenching rate by
      such a mixture exceeded that of the polypeptides in their native form. The ratio
      of the rate constants for NPY to that of the corresponding amino acid mixture in
      solution was 0.75. For melittin in its monomeric form it was 0.83 and for a
      tetramer of melittin (at high ionic strength) it was 0.70. For native insulin the
      ratio of the rate constants was 0.55. For oxidized insulin with its -S-S- bridges
      opened the figure became 0.80. However, the quenching by all the polypeptides in
      their fully denatured form (in the presence of 6 M urea) equalled that of the
      corresponding amino acid mixtures. Although polypeptides are generally supposed
      not to possess a stable secondary structure in solution the effects are explained
      by shielding of some of the reactive amino acid residues in the chain by
      temporary folding or incipient secondary structures of the native
      polypeptide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716188
TI  - Kinetic characterization of the redox components in solubilized membranes from
      porcine neutrophils: reduction with dithionite and photoexcited NAD(P)H.
AB  - Cytochrome b558 in solubilized membranes prepared from porcine neutrophils was
      reduced by dithionite with a second-order rate constant of 2.5 x 10(6) M-1 s-1 at
      pH 7.4 and 20 degrees C accompanied by spectral changes with peaks at 428 nm and
      560 nm and isosbestic points at 420 and 441 nm. When an anaerobic mixture of
      solubilized membranes and NAD(P)H was exposed to a white light, cytochrome b558
      was reduced biphasically but with almost the same spectral profiles as in the
      dithionite reduction. Thus, participation of redox component(s) of unknown nature
      in the photochemical reduction was suggested. The NAD(P). radical generated by
      photoexcitation of NAD(P)H with a 355 nm laser pulse under anaerobic conditions
      also reduced cytochrome b558 with a high rate constant of 4.3 x 10(8) M-1 s-1 at
      pH 7.4 and 20 degrees C. The reduction of cytochrome b558 accompanied a
      simultaneous reduction of a component having an absorption band around 420 nm,
      suggesting participation of an iron-sulfur (Fe-S) cluster. The cytochrome b558
      reduction was followed by its reoxidation by another component with an apparent
      second-order rate constant of 6.5 x 10(5) M-1 s-1. During the reoxidation, the Fe
      S-like component remained in the reduced state, and thus its role other than as
      electron mediator in neutrophils NADPH oxidase is suggested. Not only the rate
      constant but also the extent of cytochrome b558 reoxidation decreased as the same
      reaction mixture was exposed to the laser pulse repeatedly. This result clearly
      indicates that an electron accumulates in this electron-accepting component
      designated tentatively as the omega component.

PMID- 7716189
TI  - Unique DNA repair property of an ultraviolet-sensitive (radC) mutant of
      Dictyostelium discoideum.
AB  - Dictyostelium discoideum is an organism that shows higher UV resistance than
      other organisms, such as Escherichia coli and human cultured cells. We examined
      the removal of cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts from DNA
      in the radC mutant and the wild-type strain using an enzyme-linked immunosorbent
      assay with monoclonal antibodies. Wild-type cells excised more than 90% of both
      CPD and 6-4 photoproducts within 4 h. Dictyostelium discoideum appeared to have a
      special repair system, because 6-4 photoproducts were repaired faster than CPD in
      E. coli and human cultured cells. In radC mutant cells, although only 50% of CPD
      were excised from DNA within 8 h, effective removal of 6-4 photoproducts (80% in
      8 h) was observed. Excision repair-deficient mutants generally cannot remove both
      CPD and 6-4 photoproducts. Though the radC mutant shows deficient excision
      repair, it can remove 6-4 photoproducts to a moderate degree. These results
      suggest that D. discoideum has two kinds of repair systems, one mainly for CPD
      and the other for 6-4 photoproducts, and that the radC mutant has a defect mainly
      in the repair enzyme for CPD.

PMID- 7716190
TI  - Two genes contribute to different extents to the heme oxygenase enzyme activity
      measured in cultured human skin fibroblasts and keratinocytes: implications for
      protection against oxidant stress.
AB  - Activation of expression of the heme oxygenase (HO) gene appears to be involved
      in a cellular defense system in mammalian cells. We now demonstrate that while HO
      1 mRNA levels are strongly inducible in dermal fibroblasts they are barely
      inducible in human epidermal keratinocytes following oxidative stress (UVA
      radiation and hydrogen peroxide). Paralleling this result was the observation
      that HO-2 mRNA levels were low in dermal fibroblasts but were high in epidermal
      keratinocytes. In neither case was the HO-2 gene inducible. The expression of the
      two HO genes led to enzymatic activity in both types of skin cells with an
      approximately 2.5-fold higher level of enzymatic activity present in
      keratinocytes compared with fibroblasts derived from the same biopsy. In
      addition, ferritin levels, which have been found to be augmented via the HO
      dependent release of iron from endogenous heme sources, were two- to three-fold
      higher in keratinocytes compared with matching fibroblasts. This higher ferritin
      pool would result in an enhancement of cellular iron sequestering capacity that
      may confer increased resistance to oxidative stress. Indeed, keratinocytes showed
      less UVA radiation-dependent cell membrane damage than fibroblasts. These results
      are consistent with the hypothesis that HO expression in human epidermis and
      dermis is related to cellular defense mechanisms that operate in human skin.

PMID- 7716191
TI  - Cis-urocanic acid synergizes with histamine for increased PGE2 production by
      human keratinocytes: link to indomethacin-inhibitable UVB-induced
      immunosuppression.
AB  - There is considerable evidence that suppression of the immune system by UVB (280
      320 nm UV) irradiation is initiated by UVB-dependent isomerization of a specific
      skin photoreceptor, urocanic acid (UCA), from the trans to the cis form. Previous
      studies have confirmed that cis-UCA administration to mice 3-5 days prior to
      hapten sensitization at a distant site, suppresses the contact hypersensitivity
      (CHS) response upon challenge. This study demonstrates in mice that cis-UCA, like
      UVB, suppresses CHS to trinitrochlorobenzene by a mechanism partly dependent on
      prostanoid production. In vitro experimentation showed that human keratinocytes,
      isolated from neonatal foreskin, increased prostaglandin E2 (PGE2) production in
      response to histamine but not UCA alone. However, cis-UCA synergized with
      histamine for increased PGE2 production by keratinocytes. Cis-urocanic acid also
      increased the sensitivity of keratinocytes for PGE2 production in response to
      histamine. Prostaglandin E2 from keratinocytes exposed to cis-UCA and histamine
      may contribute directly, or indirectly, to the regulation of CHS responses by UVB
      irradiation.

PMID- 7716192
TI  - Unusually high affinity of Zn(II)-tetradibenzobarrelenooctabutoxy-phthalocyanine
      for low-density lipoproteins in a tumor-bearing mouse.
AB  - An important factor in determining the efficacy of photosensitizing compounds in
      photodynamic therapy of tumors is the level to which tumors take up the
      photosensitizers after systemic injection. This parameter seems to be related to
      the transport modalities of the photosensitizer in the bloodstream. In this work
      the photosensitizer Zn(II)-tetradibenzobarrelenooctabutoxyphthalocyanine was
      shown to have an unprecedentedly high association with low-density lipoproteins
      (71% of the phthalocyanine in the plasma) when delivered in Cremophor micelles to
      tumor-bearing mice. This was accompanied by a particularly high tumor uptake at
      24 h post-injection.

PMID- 7716193
TI  - Aggression and brain serotonergic responsivity: response to slides in male
      macaques.
AB  - The association between central serotonergic responsivity (measured by prolactin
      response to acute administration of fenfluramine hydrochloride) and aggressivity
      was examined in 40 adult male cynomolgus monkeys (Macaca fascicularis). Prolactin
      response to fenfluramine was distributed bimodally with 24 monkeys displaying a
      "low" prolactin response and 15 showing a "high" prolactin response to the
      fenfluramine challenge. Behavioral responsivity was assessed by placing the
      monkeys individually in an open-field enclosure and presenting a series of
      photographic slides depicting both threatening and nonthreatening images. Monkeys
      that were low prolactin responders displayed significantly more aggressive
      gestures in response to a threatening slide of a human being than did the high
      responders (p < 0.05). Insofar as fenfluramine-stimulated prolactin release
      assesses serotonergic responsivity, these data support related findings in people
      and nonhuman primates linking reduced serotonergic activity and aggression.

PMID- 7716194
TI  - Ingestion of amniotic fluid by postpartum rats enhances morphine antinociception
      without liability to maternal behavior.
AB  - Ingestion of amniotic fluid or placenta by rats has been shown to enhance opioid
      mediated analgesia induced by morphine injection, foot shock, vaginal/cervical
      stimulation, or late pregnancy. The present study was designed to determine
      whether this mechanism might be a means of providing greater analgesia during the
      periparturitional period without contributing to the disruption of maternal
      behavior (measured primarily as retrieval) that can result from excessive opioid
      levels. Postpartum primiparous rats, injected with either 2 or 3 mg/kg morphine
      sulfate or vehicle and given orogastric infusions of either amniotic fluid or
      saline, were tested for maternal behavior. Pain threshold (determined by tail
      flick latency test) in rats injected with 2 mg/kg morphine and infused with
      amniotic fluid was elevated to a level that did not differ significantly from
      that of a separate group of rats injected with 3 mg/kg morphine and infused with
      saline. This enhanced analgesia was not, however, accompanied by the significant
      disruption of maternal behavior found among the rats receiving the higher
      morphine dose.

PMID- 7716195
TI  - Facilitation of mating behavior in male hamsters by LHRH and AcLHRH5-10:
      interaction with the vomeronasal system.
AB  - An intact vomeronasal organ is important for the reproductive physiology and
      behavior of many species. Vomeronasal sensory input is known to influence hormone
      levels especially LH, presumably by prior modulation of LHRH. LHRH has been shown
      independently to facilitate mating behavior in rodents of both sexes. In this
      study intracerebroventricular LHRH at a dose of 50 ng substantially relieved
      mating behavior deficits caused by prepubertal removal of vomeronasal organs from
      inexperienced male hamsters. Intranasal LHRH at a higher dose did not have this
      effect. Behavioral responses were recorded 30 mins after peptide or saline
      injection. The LHRH analog, AcLHRH5-10 which we demonstrate does not induce LH
      release, did facilitate mating behavior in these tests, suggesting that LHRH
      peptides may facilitate male mating behavior via an extra-pituitary mode of
      action.

PMID- 7716196
TI  - L-tyrosine ameliorates some effects of lower body negative pressure stress.
AB  - Tyrosine, a large neutral amino acid normally present in protein foods, is the
      precursor of the catecholamine neurotransmitters dopamine, norepinephrine, and
      epinephrine. Animal studies indicate that systemic administration of tyrosine in
      pharmacological quantities can reduce physiological and behavioral decrements
      induced by highly stressful conditions. The current study was designed to test
      the effects of tyrosine (100 mg/kg of body weight) on humans exposed to
      cardiovascular stress. Twenty participants were exposed to two Lower Body
      Negative Pressure (LBNP) sessions (-50 mm Hg for a maximum of 30 min) during each
      of two testing sessions of a repeated measure double-blind placebo-controlled
      study. The detected effects of tyrosine include an overall increase in pulse
      pressure (LBNP typically reduces pulse pressure) and an increase in auditory
      event related potential amplitude (P300-N300), an electro-physiological correlate
      of attention which may indicate enhanced cognitive activation.

PMID- 7716197
TI  - Sodium intake linked to amiloride-sensitive gustatory transduction in C57BL/6J
      and 129/J mice.
AB  - Mice of 129/J and C57BL/6J inbred strains received two-bottle, 48-h preference
      tests of NaCl solutions vs. distilled water. 129/J mice exhibited a greater
      preference for 0.08 M NaCl than did C57BL/6J mice. To determine if this strain
      difference was mediated by taste, the integrated neural responses of the chorda
      tympani nerve to a concentration range of NaCl and KCl were examined. Gustatory
      neural responses to NaCl were similar for 129/J and C57BL/6J mice. However,
      lingual application of 0.5 mM amiloride hydrochloride significantly suppressed
      chorda tympani responses to a range of NaCl concentrations in C57BL/6J mice but
      did not do so consistently in 129/J mice. Amiloride failed to significantly
      suppress responses to a range of KCl concentrations in both mouse strains. The
      results suggest that for 129/J mice, sodium reception and transduction are
      primarily amiloride insensitive, whereas for C57BL/6J mice, both amiloride
      sensitive and amiloride-insensitive components are present. The strain difference
      in NaCl intake may be mediated, in part, through gustatory mechanisms, with
      reduced preference for NaCl influenced by amiloride-sensitive sodium transduction
      mechanisms.

PMID- 7716198
TI  - Sucrose consumption as an hedonic measure following chronic unpredictable mild
      stress.
AB  - The consumption of, and preference for, a rewarding 0.9% sucrose solution was
      examined in rats subjected chronically (8 wk) to a regimen of unpredictable mild
      stressors. Intake of sucrose was reduced in stressed animals compared to controls
      after 3 wk. However, correction for body weight changes revealed no significant
      difference in sucrose consumption between the groups. A comparison of the mean
      sucrose intakes of matched low-weight rats, with low weight a function of either
      immaturity or stress, failed to differentiate between the groups. Total sucrose
      consumption and total fluid intake correlated significantly with body weight of
      stressed animals and controls. Percentage preference for sucrose solution did not
      differ between controls and stressed animals. It is concluded that the validity
      and reliability of sucrose consumption as an hedonic measure within the context
      of exposure to chronic unpredictable mild stress must be questioned.

PMID- 7716199
TI  - Fat mobilisation in short days is not associated with altered noradrenergic
      sensitivity of adipocytes in Djungarian hamsters.
AB  - One of the primary physiological responses of the Djungarian hamster to short
      photoperiods is a reduction in body weight with fat mobilisation. The depletion
      of fat to a minimum level may be regulated either in the periphery, through the
      sensitivity of adipocytes to hormonal stimulation, or centrally, via adjustments
      in efferent activity. To investigate this, we examined the lipolytic pathway in
      fat cells from animals at various stages of entrainment to long or short
      photoperiod. Short photoperiod exposure of up to a 10-week duration was without
      effect on basal glycerol release by unstimulated cells or on the ability of
      norepinephrine or an adenosine analogue to stimulate or inhibit lipolysis,
      respectively. Prolonged exposure to short photoperiod reduced basal glycerol
      release, but adipocytes retained their sensitivity to hormonal stimulation. Short
      photoperiod had no effect on the density or affinity of membrane-bound beta
      adrenergic or adenosine receptors, or upon the ability of isoproterenol or
      forskolin to stimulate adenylate cyclase in adipocyte membranes. This suggests
      that the regulation of fat depletion in short photoperiod is determined centrally
      and does not involve alterations in adipocyte sensitivity and, in particular, the
      desensitisation of the adipocyte beta-adrenergic receptor-linked adenylate
      cyclase pathway.

PMID- 7716201
TI  - Blockade of digestion by famotidine pretreatment does not interfere with the
      opioid-enhancing effect of ingested amniotic fluid.
AB  - Ingestion of placenta or amniotic fluid by rats has been shown to enhance ongoing
      opioid-mediated antinociception, but does not, by itself, produce
      antinociception. This enhancement is produced by an active substance(s) in
      placenta and amniotic fluid that we have termed POEF for placental opioid
      enhancing factor. Previous research has shown that enhancement requires mediation
      by the gastrointestinal system: gastric vagotomy blocks enhancement produced by
      ingested placenta; amniotic fluid injected SC or IP does not produce enhancement.
      The present study was designed to distinguish between two possible explanations
      for the blockade of the POEF effect produced by gastric vagotomy: that afferent
      information arising in vagal gastric receptors conveys the critical information
      to the CNS, or that disruption of vagal efferent action on digestion blocks the
      manufacture or activation of the POEF molecule in the gut. Famotidine is an H2
      histamine receptor antagonist that reduces gastric acid and pepsin secretion to
      an extent at least as great as gastric vagotomy. Rats treated with either
      famotidine or a vehicle were fed placenta or a control substance, then stimulated
      with vaginal/cervical probing to produce antinociception that is partly opioid
      mediated. Famotidine did not block POEF enhancement of vaginal/cervical
      stimulation-induced analgesia in a tail flick latency test. These results suggest
      that enhancement by POEF does not require normal digestive processes or other
      processes inhibited by famotidine.

PMID- 7716200
TI  - Olfactory sensitivity to the pheromone, androstenone, is sexually dimorphic in
      the pig.
AB  - Sexually dimorphic pheromone pathways have been used successfully to study insect
      olfactory coding. As one of the few mammalian species with an identified sex
      pheromone, the domestic pig (Sus scrofa) may be an ideal vertebrate species in
      which to examine sex differences in olfactory processing of a specific stimulus.
      In this experiment, androstenone and control odor detection thresholds were
      measured in adult male, female, and castrated male pigs. In an operant task, pigs
      were tested with descending concentration series of both androstenone and
      geraniol. All groups were equally sensitive to geraniol, but there was a sex
      difference in sensitivity to the odor of androstenone. Female pigs' detection
      threshold was a dilution fivefold lower than the threshold for intact males.
      Castrated males did not differ significantly from either males or females. This
      is the first example of a sexual dimorphism in sensitivity to a mammalian
      pheromone.

PMID- 7716202
TI  - Surfeit calories during parenteral nutrition influences food intake and carcass
      adiposity in rats.
AB  - The relationship between surfeit caloric consumption during intravenous infusion
      of a parenteral nutrition solution providing 100% daily caloric needs (PN-100;
      glucose:fat:amino acid = 50:30:20), carcass adiposity, and postinfusion food
      intake was evaluated. Rats received saline (control) or PN-100 for 4 days via
      jugular vein. PN-100 rats were either allowed or denied access to chow during the
      infusion period. When food was available during the 4 days of PN-100, total
      cumulative caloric intake, eaten and infused, was 40% higher than controls (p <
      0.01). Percent carcass adiposity was increased from 8.8% to 11.6% (p = 0.04), and
      there was a 3-day delay before food intake returned to baseline. When caloric
      intake was limited to that provided by PN-100, carcass adiposity was not
      increased and food intake was 86% of baseline during the first 24 h after
      stopping PN-100. Delayed return of normal food intake following PN-100 is the
      likely consequence of excess caloric ingestion during the PN-100 infusion period.
      The surfeit caloric intake resulted in increased carcass adiposity.

PMID- 7716203
TI  - Measurement and seasonal variations of black bear adipose lipoprotein lipase
      activity.
AB  - The black bear (Ursus americanus) provides a unique model for the study of
      adipose physiology because it exhibits seasonal periods of rapid weight gain and
      weight loss without marked changes in its metabolic rate. To better understand
      fat cycling in this model, we obtained plasma and gluteal adipose tissue from
      five captive adult bears at approximately 20-day intervals from October 1 1992
      through March 31 1993. The study included a predenning and denning period for
      each animal. Sampling during the predenning period followed a 12-h fast. Bears
      were anorectic while denning. Adipose LPL activities and plasma insulin
      concentrations were determined for each time point. Predenning LPL activities
      (4.83 +/- 0.64 mumol/h/g) were significantly greater than those seen during the
      denning period (1.82 +/- 0.65, p < 0.001). A biphasic pattern of fasting LPL
      activity was seen in four of the five bears during the predenning period. Fasting
      insulin concentrations showed no such pattern of variation during the study
      period (mean = 25.1 +/- 1.36 pmol/l; range 1.1-6.0). We found no evidence of a
      linear relationship between LPL activity and insulin levels (p = 0.139). Neither
      LPL activity nor insulin concentrations were related to changes in weight (p =
      0.257 and p = 0.7104, respectively). We conclude that LPL activity can be
      measured in black bear adipose tissue and that fall (predenning) activities are
      significantly higher than those seen during the winter (denning period).
      Furthermore, the seasonal regulation of LPL involves some factor(s) in addition
      to insulin.

PMID- 7716204
TI  - Metabolic changes associated with ingestion of different macronutrients and
      different meal sizes in rats.
AB  - Indirect calorimetry was used to investigate whole-body metabolic changes
      occurring during and after feeding in the rat. Measurement of respiratory
      exchange allowed the derivation of respiratory quotient (RQ = CO2 produced/O2
      consumed) and energy expenditure [EE = O2 consumed (364 + 113RQ)], giving an
      estimate of the energy substrate (fat, carbohydrate, or protein) being utilised
      and the total substrate oxidation occurring, respectively. Concurrent measurement
      of locomotor activity (ACT) allowed the changes in EE attributable to feeding
      (postprandial thermogenesis) to be generally dissociated from those attributable
      to activity. Experiment 1 examined alterations in RQ, EE, and ACT following brief
      (< 5 min) calorically matched meals of Froot Loops (86% carbohydrate), casein
      (protein), lard (fat) and lab chow (mixed macronutrient) and following the
      ingestion of 0.1% saccharin (which is calorically inert). Rapid (< 5 mins) and
      sustained increases in RQ occurred following Froot Loop and lab chow meals
      indicating increased utilization of carbohydrates as an energy substrate. Casein
      caused little change in RQ, while lard caused a drop in RQ approximately 30 min
      following ingestion, indicating increased fat utilization following absorption of
      the lard meal. Saccharin caused little change in RQ, suggesting that a sweet
      taste is not sufficient to alter substrate utilization. Increased EE was seen
      following the Froot Loops and lab chow meals in the absence of corresponding
      increases in ACT, suggesting a postprandial thermogenic effect of these meals. In
      Experiment 2, the metabolic changes accompanying a large (5 g) and small (0.5 g)
      Froot Loops meal were compared. The large meal resulting in a larger, more rapid
      and more sustained increase in RQ than the small meal. In addition, there was an
      increase in EE in the absence of corresponding increases in ACT following the
      large meal suggesting the presence of postprandial thermogenesis. It is concluded
      that both meal macronutrient content and meal size are important determinants of
      postprandial substrate utilization and thermogenesis in rats.

PMID- 7716205
TI  - The relationship of cognitive restraint to the spontaneous food and fluid intake
      of free-living humans.
AB  - How the desire to restrain intake, cognitive restraint, may influence the amount
      or pattern of food and fluid intake was investigated by studying the spontaneous
      intake of free-living humans. The Three-Factor Eating Questionnaire and the
      Restraint Scale were completed by 358 adults who also were paid to maintain 7-day
      diaries of their intake. For both males and females, higher cognitive restraint
      ws associated with lower and less variable overall intake, especially of fat and
      carbohydrate. This resulted from the ingestion of smaller and less variable meals
      that contained less fat. In addition, high restraint was associated with smaller
      deprivation ratios, and lower estimated before and after meal stomach contents.
      Although females were higher in restraint than males, comparable levels of
      restraint had equivalent effects upon intake. The results suggest that restrained
      subjects simply eat less because they require less with cognitive restraint as a
      secondary consequence.

PMID- 7716206
TI  - A gerbil dam's fetal intrauterine position affects the sex ratios of litters she
      gestates.
AB  - The vaginally delivered litters of gerbil dams that, in utero, occupied
      intrauterine positions between two males fetuses (2M females) contain a greater
      proportion of sons than do the vaginally delivered litters of gerbil dams that
      were gestated between two female fetuses (2F females). This difference in the sex
      ratios of litters delivered vaginally by 2M and 2F gerbils might reflect sex
      biased differences in perinatal mortality in the litters of 2M and 2F dams.
      However, the results of the present experiment, in which gerbil litters were
      delivered by caesarian section from females that developed in 2M and 2F
      intrauterine positions, demonstrated unequivocally that 2M female gerbils gestate
      male-biased litters, whereas 2F female gerbils gestate female-biased litters.

PMID- 7716207
TI  - Differential open field reactivity in HAS and LAS rats.
AB  - To identify potential differences in emotional reactivity in high (HAS) and low
      (LAS) alcohol-sensitive rats in open field tests, 20 ethanol naive, 19th
      generation HAS and 20 LAS rats from the University of Colorado's Alcohol Research
      Center each received three consecutive daily 20-min exposures to a 1-sq m open
      field. The results of repeated-measures ANOVA and Keuls tests, performed on each
      of five concurrently recorded behaviors, indicated that, compared to HAS rats,
      LAS animals exhibited significantly greater latencies to begin ambulation,
      elevated ambulation, and rearing scores that failed to habituate over 3 days, and
      an increasing intersession bolus count. In addition, significant positive
      correlations occurred between days 2 + 3 (but not day 1) ambulation and bolus
      counts in LAS but not HAS rats, and between day 1 ambulation and (i) rearings and
      (ii) center square entries in HAS but not LAS rats. Together with other cited
      data, these results provide support for a hypothesis of relatively greater
      emotional reactivity in LAS rats and illustrate the need for multiple measures
      and sessions in evaluating open field behavior.

PMID- 7716208
TI  - Progesterone modulation of androgen-dependent sexual behavior in male rats.
AB  - The present study examines the effects of physiological levels of progesterone
      (P) on copulatory behavior in sexually naive male rats. Two weeks after
      gonadectomy males were implanted with either empty Silastic capsules (BL) or
      Silastic capsules containing testosterone (T), P, or both (P+T). When tested with
      an estrous female, all of the gonadally intact males (intact) and none of the BL
      controls exhibited mounting/intromission behaviors. Mounting was observed in 75%
      of the T-alone males. More than half (64%) of the P-alone males and 100% P+T
      males exhibited mounting. In most cases, mounting was followed by intromission
      responses. Subsequently, intact and gonadectomized males received daily
      injections of the P antagonist RU486 along with hormone treatment. After
      receiving RU486, only 63% of the intact males and 71% of the T-alone males
      mounted successfully. The facilitatory effects of P on copulatory behavior were
      completely abolished by RU486 treatment. The present studies provide the first
      evidence in mammals suggesting that P-dependent mechanisms influence
      neurochemical pathways involved in copulation.

PMID- 7716209
TI  - Effect of fetal hypoxia on seizure susceptibility in rats.
AB  - In the present study, susceptibility to Pentylentetrazol (PTZ)-induced seizures
      was tested in 45 four-wk old rats born to mothers exposed to moderate asphyxia in
      the last week of pregnancy by breathing N2 99.9% for 6 min in two separate
      sessions, (Group I--experimental rats) and in 44 rats of the same age, born after
      a normal pregnancy (Group II--controls). The results showed that the experimental
      rats, following episodes of asphyxia in intrauterine life, had a higher
      susceptibility to PTZ-induced seizures than the controls, manifested by earlier
      onset of convulsions and a higher incidence of fetal epileptic status. This
      occurred despite normal development and the absence of neurological deficits in
      the experimental rats in the first 4 wk of extrauterine life.

PMID- 7716211
TI  - Frequency of the 22 kHz call of rats is modulated by the rhythm of the heart
      rate.
AB  - The 22 kHz calls of rats are rhythmically frequency modulated. To test whether
      these modulations are correlated with the action of the heart, ECG was
      chronically registered in 16 male Wistar rats. In 11 rats loud acoustic stimuli
      provoked emission of the long calls or 22 kHz calls. In 10 self-vocalizing rats,
      we observed small frequency modulations (SFMs) in the constant frequency
      component of these calls. On the average, 7 ms after the R-peak of the ECG the
      call frequency is lowered by 151 Hz. The heart rate and the rate of the SFMs are
      highly correlated (r = 0.997). Further, we show that the SFMs are produced by a
      reduction of call amplitude. The comparison with the course of the blood pressure
      in rats suggests that this change in call amplitude is caused by the blood
      pressure change during the action of the heart. Measuring SFMs offers a
      noninvasive way to determine the heart rate in vocalizing rats.

PMID- 7716210
TI  - Comparison of TOBEC-derived total body fat with fat pad weights.
AB  - Total body electrical conductivity (TOBEC) predictions of overall body fat were
      compared to combined perirenal and epididymal fat pad weights. The latter are
      considered to be reasonable estimates of overall adiposity. TOBEC was used to
      measure the body composition of 40 male Long-Evans and two male Sprague-Dawley
      rats ranging in weight from 210-505 g. The animals were then sacrificed and the
      perirenal and epididymal fat pads were removed and weighed. Core temperature was
      recorded before and after TOBEC values were collected. To assess the effect of
      position, two values were obtained for young rats: one when the tail was tucked
      under the rat's body and another when the tail was extended such that the full
      length of the measurement chamber was occupied. The TOBEC-predicted body fat was
      significantly different for these two positions. The best correlation between fat
      pad weight and TOBEC-predicted body fat (r = 0.83) was obtained when young
      animals were in the tail-extended position. The reliability of TOBEC readings
      appears to be reasonably good with mature rats.

PMID- 7716212
TI  - Endocrine sensitivity to novelty in squirrel monkeys and titi monkeys: species
      differences in characteristic modes of responding to the environment.
AB  - The present study examined plasma cortisol and behavioral responses to
      environmental novelty in squirrel monkey and titi monkey male-female pairs.
      Overall, seemingly trivial increments in novelty evoked sustained plasma cortisol
      elevations. In individually tested animals, the minimal level of novelty
      sufficient to evoke a cortisol response was smaller, and the ability of the
      response to discriminate among levels of novelty was greater, in titis than in
      squirrel monkeys. When tested with the pairmate, the sensitivity of the response
      was reduced in titis but not in squirrel monkeys. Behavioral measures were not as
      sensitive to novelty as was the cortisol response. The results suggest that
      differential endocrine responsiveness to novelty is an important physiological
      concomitant to previously described differences between squirrel monkeys and titi
      monkeys in their characteristic modes of relating to the environment.

PMID- 7716213
TI  - Endogenous oscillator and regulatory mechanisms of body temperature in sheep.
AB  - To determine the influence of various feeding schedules (different times of
      feeding, times without feeding) on the time course of heart rate (HR), electric
      activity of cervical muscles (EMG), motor activity (ACT) and body temperature
      (TB) in ruminants, 5 sheep were equipped with portable dataloggers able to
      register and store these variables every 30s. Under controlled housing
      conditions, the temporal changes which occur were registered for 12 consecutive
      days each period at least. During experimental periods with various feeding times
      HR and TB were within the physiological range and all variables showed pronounced
      peaks which were associated with the time of food presentation. On days without
      feeding TB (38.8 degrees C) was at the lower limit of this range and HR (56 bpm)
      was extremely below this limit; similar peaks as before were not detectable. The
      circadian rhythms of HR and TB seemed not to be influenced by the different times
      of feeding, but there were hints, that photic or social factors could act as a
      zeitgeber for ACT. Remarkable was the fact that the downregulation of the food
      induced rises of HR and TB was determined by the phase angle of the circadian
      rhythm.

PMID- 7716214
TI  - Oral satiation and regulation of intake.
AB  - The satiating effect of maltose and glucose was tested following oral
      application. Results showed significant suppression of subsequent cereal intake
      for both. Based on this finding, oral satiation is proposed to be the first and
      perhaps the most important in a sequence of mechanisms for regulating nutrient
      intake. Sensory recognition based on chemical structure rather than special
      attributes such as calorie content is proposed as the basis for this mechanism.
      Lactose and sucrose, two other sugars important in human nutrition, may also
      function in a similar manner.

PMID- 7716215
TI  - Interest in infants varies with reproductive condition in group-living female
      pigtail macaques (Macaca nemestrina).
AB  - Previous studies of macaques have failed to show a relationship between female
      reproductive condition and infant-directed behavior. This has led to the view
      that maternal responsiveness in nonhuman primates is independent from hormonal
      variables and is mainly regulated by social and experiential factors. The present
      study reports longitudinal data on interactions between group-living adult
      pigtail macaque females and other females' infants less than 12 weeks of age
      during the 6 weeks prior to conception, the 24 weeks of pregnancy, and the first
      12 weeks of lactation. These periods represent different hormonal conditions in
      the reproductive cycle. Infant-directed behavior increased in frequency during
      early and middle pregnancy, decreased around the time of parturition, and
      increased again during lactation. The frequency of infant-directed behavior also
      increased significantly in the 2 weeks after infant loss during lactation. These
      results are in accord with recent evidence in New World monkeys indicating that
      maternal responsiveness in nonhuman primates develops during pregnancy and it is
      probably hormonally regulated.

PMID- 7716216
TI  - Effects of chronic stress on sleep in rats.
AB  - The present study was conducted to determine the effects of chronic stress on
      sleep using a rodent paradigm of around-the-clock signalled intermittent foot
      shock in which some rats can pull a chain to avoid/escape shock while another
      group of rats is yoked to the first group. We measured sleep using telemetry;
      four-channel EEG was collected 24 h/day in rats during 2 prestress days; days 1,
      2, 3, 7, and 14 during chronic stress; and 3 poststress days. States of REM
      sleep, non-REM (NREM) sleep, and waking were scored for each 15-s period of the
      EEG recordings. During the prestress period, rats slept (REM plus NREM) 55% of
      available time during the light hours and 34% of the dark hours with the
      remainder represented by waking. On the first day of stress, total sleep and,
      especially REM sleep, decreased markedly. By the second day of stress, only REM
      sleep in the controllable stress group (but not the uncontrollable stress group)
      was still significantly decreased compared to prestress levels, and REM sleep
      returned to baseline levels by day 7 of stress. The recovery of sleep quantity
      was accomplished by increased sleep during the dark hours, resulting in a long
      lasting disruption of normal circadian sleep patterning.

PMID- 7716217
TI  - Effect of aspartate, asparagine, and carnitine supplementation in the diet on
      metabolism of skeletal muscle during a moderate exercise.
AB  - The present study examined the effect of diet supplementation of oxaloacetate
      precursors (aspartate and asparagine) and carnitine on muscle metabolism and
      exercise endurance. The results suggest that the diet supplementation increased
      the capacity of the muscle to utilize FFA and spare glycogen. Time to exhaustion
      was about 40% longer in the experimental group compared to the control, which
      received commercial diet only. These findings suggest that oxaloacetate may be
      important to determine the time to exhaustion during a prolonged and moderate
      exercise.

PMID- 7716218
TI  - Effect of imagining and actually tasting a sour taste on one side of the tongue.
AB  - To determine whether images can stimulate brainstem reflexes directly, parotid
      salivation was measured bilaterally in 24 subjects when they imagined, and
      actually tasted, a sour taste on one side of the tongue. Salivation increased in
      both cheeks during unilateral gustatory stimulation; furthermore, the response
      was greater on the stimulated side than contralaterally, indicating that the
      gustatory reflex has a unilateral component. Subjects imagined the sour taste
      more clearly after actually experiencing it. However, salivation did not increase
      significantly during imagery trials, either before or after exposure to the sour
      taste; in fact, salivation to imagery decreased below baseline after exposure.
      These findings suggest that extraneous factors (e.g. the emotional connotations
      of images, anxiety, discomfort, repetitive measurement or fatigue) might
      sometimes inhibit specific reflex activity induced by images.

PMID- 7716219
TI  - Short-term effects of high-fat and low-fat/high-SPE croissants on appetite and
      energy intake at three deprivation periods.
AB  - The short-term satiating effects of croissants with different amounts of fat and
      sucrose polyester (SPE) followed by three lengths of deprivation were
      investigated. Sixteen male and 18 female normal-weight subjects each received six
      different experimental conditions in a two x three factorial design. Energy
      content was the first factor with two levels: 1.80 MJ and 3.45 MJ. The second
      factor was the deprivation period after the lunch preload with three levels:
      0.25, 2.25, and 4.75 h. Subjects ate ad lib after the deprivation period. The
      effects of the croissants were determined by motivational ratings and reported
      food consumption on the study day and the day after the study day. The SPE
      croissants (1.80 MJ) and the high-fat croissants (3.45 MJ) did not result in
      different subsequent energy intakes. Differences in energy intake were found
      between the three deprivation conditions, with the lowest intake with the 4.75-h
      deprivation condition. This was due to differences in the energy intake during
      the afternoon. The two energy levels of the preloads had similar effects on the
      motivational ratings. Higher appetite ratings were found after the 4.75-h
      compared to the 0.25 h and the 2.25-h deprivation condition.

PMID- 7716220
TI  - Lack of sex and estrous cycle effects on the activity of three antioxidant
      enzymes in rats.
AB  - The activity of antioxidant enzymes was investigated in red blood cells of male
      and female Wistar rats 3-4 months of age. Superoxide dismutase (EC 1.15.1.1),
      catalase (EC 1.11.1.6), and glutathione peroxidase (EC 1.11.1.9) did not show any
      significant variation in the different phases of the estrous cycle. No
      differences were observed for the three enzymes related to the sex of young rats.
      The present data enable us to consider that sexual differences as well as the
      changes in estrous cycle do not interfere in erythrocyte antioxidant enzymatic
      defense of rats.

PMID- 7716222
TI  - Ginsenoside Rg1 modulates ingestive behavior and thermal response induced by
      interleukin-1 beta in rats.
AB  - Effects of ginsenoside Rg1 (Rg1), a major component of panax ginseng, on changes
      in ingestive behavior and rectal temperature induced by interleukin-1 beta (IL-1
      beta) were investigated in rats. Intraperitoneal (ip) injection of IL-1 beta
      suppressed food and water intake and elevated rectal temperature. The suppressive
      effect of IL-1 beta on water intake was converted to an increase when 4.0 mM Rg1
      was continuously infused into the third cerebroventricle (ICV) at a rate of 0.966
      microliters/h. The elevation of rectal temperature induced by IL-1 beta was
      attenuated by ICV infusion of Rg1. The feeding suppression caused by IL-1 beta
      was unaffected by ICV infusion of Rg1. These results suggest that sustained ICV
      infusion of Rg1 may modulate the effects of IL-1 beta on ingestive behaviors,
      i.e., increase in water intake and sustained decrease in food intake, resulting
      in a lowering of body temperature.

PMID- 7716221
TI  - Effects of ketamine, a noncompetitive NMDA antagonist, on the acquisition of the
      lever-press response in rats.
AB  - We analyzed the effects of ketamine, a noncompetitive NMDA antagonist, on the
      acquisition of the lever-press response in the Skinner box and on motor
      performance both in the open field and in the inclined screen. Ninety-six adult
      male Wistar rats were assigned at random to eight different groups (n = 12). The
      first four groups received an acute intraperitoneal (IP) injection of: (a)
      physiological saline, (b) 4 mg/kg ketamine, (c) 8 mg/kg ketamine, or (d) 12 mg/kg
      ketamine, and the subjects were tested in a free lever-press response shaping in
      the Skinner box. The second four groups received the same substances and doses as
      the first four, but the subjects were tested for locomotor activity in an open
      field and tested immediately afterwards for motor performance in an 80 degrees
      inclined screen. Results showed that ketamine impaired the acquisition of the
      lever-press response in a dose-dependent manner, with no effects on ambulation in
      the open field nor on length of stay in the inclined screen. These results
      suggest that ketamine effects on the acquisition of the lever-press response
      cannot be attributed to a motor impairment, indicating a possible specific effect
      of ketamine on the associative learning acquisition.

PMID- 7716223
TI  - Maternal behavior of dams treated with ACTH during pregnancy.
AB  - Experimental female rats were injected with ACTH during the last third of their
      pregnancy. This treatment resulted in prolongation of gestation and in abnormal
      development of the young. The number of resorptions, stillbirths, and
      congenitally malformed pups was increased and those that appeared normal had
      lower body weights. The experimental treatment also severely affected the ability
      of the dams to exhibit normal maternal behavior. Significant individual
      differences were noted in the sensitivity of the dams to the experimental
      treatment. Cross-fostering experiments revealed that experimental dams exhibited
      normal maternal behavior towards control foster pups, after an initial delay of
      24 h. When experimental pups, born after a prolonged gestation, or delivered by
      caesarian section after the normal duration of gestation, were given to control
      mothers, normal maternal behavior was observed, but the survival rate of the
      young was not increased.

PMID- 7716224
TI  - Behavioral conditioning of lipopolysaccharide-induced anorexia.
AB  - One manifestation of the acute phase response, sickness behavior, is now
      considered an important response in the organism's overall attempt to reinstate
      homeostasis. This report aimed to determine whether the sickness behavior of
      anorexia was conditionable using the conditioned taste aversion paradigm. To
      investigate this phenomenon, lipopolysaccharide (LPS) (100 micrograms/kg) was
      used as the unconditioned stimulus, and was paired with a novel 1% saccharin
      solution (conditioned stimulus). Upon conditioned stimulus representation, the
      anorectic effects of LPS were observed. These data are consistent with recent
      literature showing acute phase events to be conditionable.

PMID- 7716225
TI  - Effect of neonatal handling on learned helplessness model of depression.
AB  - The present study was undertaken to investigate the effects of neonatal handling
      on learned helplessness (LH) model of depression in the rat. We also investigated
      the effect of neonatal handling on behavior in an open field test of
      emotionality. The handling procedure reduced helplessness behavior, with a
      decrease in the number of escape failures, an increase in the number of avoidance
      responses, and a decrease in the escape latency in the shuttle-box after
      induction of LH. In addition, handling during infancy decreased the number of
      boli in an open field test, which suggests that the level of emotivity in
      adulthood was reduced. It is suggested that handling in infancy improves
      behavioral adaptation to the environment, including enhanced adaptive response to
      stress.

PMID- 7716226
TI  - Sequence of actin cDNA from Fucus disticus.

PMID- 7716227
TI  - Cloning of a full-length cDNA for malic enzyme (EC 1.1.1.40) from grape berries.

PMID- 7716229
TI  - Molecular cloning of the biotinylated subunit of 3-methylcrotonyl-coenzyme A
      carboxylase of Arabidopsis thaliana.

PMID- 7716228
TI  - A Zea mays pollen cDNA encoding a putative actin-depolymerizing factor.

PMID- 7716230
TI  - Isolation of a new member of the soybean Kunitz-type proteinase inhibitors.

PMID- 7716231
TI  - A full-length cDNA encoding 1-aminocyclopropane-1-carboxylate synthase from
      apple.

PMID- 7716232
TI  - Flavonol sulfotransferase-like cDNA clone from Flaveria bidentis.

PMID- 7716233
TI  - Cloning and nucleotide sequence of a cDNA encoding S-adenosyl-L-methionine
      synthetase from mustard (Brassica juncea [L.] Czern & Coss).

PMID- 7716234
TI  - Cloning and sequencing of chickpea cDNA coding for threonine deaminase.

PMID- 7716235
TI  - Nucleotide sequence of cDNA for a putative cysteine protease from rice seeds.

PMID- 7716236
TI  - Medicago sativa cDNAs encoding chalcone reductase.

PMID- 7716237
TI  - An Arabidopsis cDNA related to animal phosphoinositide-specific phospholipase C
      genes.

PMID- 7716238
TI  - Nucleotide sequence of four ribosomal protein L27 cDNAs from growing axillary
      buds of pea.

PMID- 7716239
TI  - A cDNA clone for 5-aminolevulinic acid dehydratase from tomato (Lycopersicon
      esculentum Mill.).

PMID- 7716240
TI  - Nucleotide sequence of additional members of the gene family encoding chalcone
      synthase in Trifolium subterraneum.

PMID- 7716241
TI  - Short duplication in a cDNA clone of the rbcL gene from Picea abies.

PMID- 7716242
TI  - Cloning and sequencing of a full-length cDNA coding for sn-glycerol-3-phosphate
      acyltransferase from Phaseolus vulgaris.

PMID- 7716244
TI  - The bark of Robinia pseudoacacia contains a complex mixture of lectins.
      Characterization of the proteins and the cDNA clones.
AB  - Two lectins were isolated from the inner bark of Robinia pseudoacacia (black
      locust). The first (and major) lectin (called RPbAI) is composed of five
      isolectins that originate from the association of 31.5- and 29-kD polypeptides
      into tetramers. In contrast, the second (minor) lectin (called RPbAII) is a
      hometetramer composed of 26-kD subunits. The cDNA clones encoding the
      polypeptides of RPbAI and RPbAII were isolated and their sequences determined.
      Apparently all three polypeptides are translated from mRNAs of approximately 1.2
      kb. Alignment of the deduced amino acid sequences of the different clones
      indicates that the 31.5- and 29-kD RPbAI polypeptides show approximately 80%
      sequence identity and are homologous to the previously reported legume seed
      lectins, whereas the 26-kD RPbAII polypeptide shows only 33% sequence identity to
      the previously described legume lectins. Modeling the 31.5-kD subunit of RPbAI
      predicts that its three-dimensional structure is strongly related to the three
      dimensional models that have been determined thus far for a few legume lectins.
      Southern blot analysis of genomic DNA isolated from Robinia has revealed that the
      Robinia bark lectins are the result of the expression of a small family of lectin
      genes.

PMID- 7716243
TI  - Phytochrome A overexpression in transgenic tobacco. Correlation of dwarf
      phenotype with high concentrations of phytochrome in vascular tissue and
      attenuated gibberellin levels.
AB  - Phytochromes are a family of related chromoproteins that regulate
      photomorphogenesis in plants. Ectopic overexpression of the phytochrome A in
      several plant species has pleiotropic effects, including substantial dwarfing,
      increased pigmentation, and delayed leaf senescence. We show here that the dwarf
      response is related to a reduction in active gibberellins (GAs) in tobacco
      (Nicotiana tabacum) overexpressing oat phytochrome A under the control of the
      cauliflower mosaic virus (CaMV) 35S promoter and can be suppressed by foliar
      applications of gibberellic acid. In transgenic seedlings, high concentrations of
      oat phytochrome A were detected in stem and petiole vascular tissue (consistent
      with the activity of the CaMV 35S promoter), implicating vascular tissue as a
      potential site of phytochrome A action. To examine the efficacy of this cellular
      site, oat phytochrome A was also expressed using Arabidopsis chlorophyll a/b
      binding protein (CAB) and the Arabidopsis ubiquitin (UBQ1) promoters. Neither
      promoter was as effective as CaMV 35S in expressing phytochrome in vascular
      tissue or in inducing the dwarf phenotype. Collectively, these data indicate that
      the spatial distribution of ectopic phytochrome is important in eliciting the
      dwarf response and suggest that the phenotype is invoked by elevated levels of
      the far-red-absorbing form of phytochrome within vascular tissue repressing GA
      biosynthesis.

PMID- 7716246
TI  - Sugar-inducible expression of a gene for beta-amylase in Arabidopsis thaliana.
AB  - The levels of beta-amylase activity and of the mRNA for beta-amylase in rosette
      leaves of Arabidopsis thaliana (L.) Heynh. increased significantly, with the
      concomitant accumulation of starch, when whole plants or excised mature leaves
      were supplied with sucrose. A supply of glucose or fructose, but not of mannitol
      or sorbitol, to plants also induced the expression of the gene for beta-amylase,
      and the induction occurred not only in rosette leaves but also in roots, stems,
      and bracts. These results suggest that the gene for beta-amylase of Arabidopsis
      is subject to regulation by a carbohydrate metabolic signal, and expression of
      the gene in various tissues may be regulated by the carbon partitioning and sink
      source interactions in the whole plant. The sugar-inducible expression of the
      gene in Arabidopsis was severely repressed in the absence of light. The sugar
      inducible expression in the light was not inhibited by 3(3,4-dichlorophenyl)-1,1
      dimethylurea or by chloramphenicol, but it was inhibited by cycloheximide. These
      results suggest that a light-induced signal and de novo synthesis of proteins in
      the cytoplasm are involved in the regulation. A fusion gene composed of the 5'
      upstream region of the gene for beta-amylase from Arabidopsis and the coding
      sequence of beta-glucuronidase showed the sugar-inducible expression in a light
      dependent manner in rosette leaves of transgenic Arabidopsis.

PMID- 7716245
TI  - The effects of mastoparan on the carrot cell plasma membrane polyphosphoinositide
      phospholipase C.
AB  - When [3H]inositol-labeled carrot (Daucus carota L.) cells were treated with 10 or
      25 microM wasp venom peptide mastoparan or the active analog Mas-7 there was a
      rapid loss of more than 70% of [3H]phosphatidylinositol-4-monophosphate (PIP) and
      [3H]phosphatidylinositol-4,5-bisphosphate (PIP2) and a 3- and 4-fold increase in
      [3H]inositol-1,4-P2 and [3H]inositol-1,4,5-P3, respectively. The identity of
      [3H]inositol-1,4,5-P3 was confirmed by phosphorylation with inositol-1,4,5-P3 3
      kinase and co-migration with inositol-1,3,4,5-P4. The changes in
      phosphoinositides were evident within 1 min. The loss of [3H]PIP was evident only
      when cells were treated with the higher concentrations (10 and 25 microM) of
      mastoparan or Mas-7. At 1 microM Mas-7, [3H]PIP increased. The inactive
      mastoparan analog Mas-17 had little or no effect on [3H]PIP or [3H]PIP2
      hydrolysis in vivo. Neomycin (100 microM) inhibited the uptake of Mas-7 and
      thereby inhibited the Mas-7-stimulated hydrolysis of [3H]PIP and [3H]PIP2. Plasma
      membranes isolated from mastoparan-treated cells had increased PIP-phospholipase
      C (PLC) activity. However, when Mas-7 was added to isolated plasma membranes from
      control cells, it had no effect on PIP-PLC activity at low concentrations and
      inhibited PIP-PLC at concentrations greater than 10 microM. In addition,
      guanosine-5'-O-(3-thiotriphosphate) had no effect on the PIP-PLC activity when
      added to plasma membranes isolated from either the Mas-7-treated or control
      cells. The fact that Mas-7 did not stimulate PIP-PLC activity in vitro indicated
      that the Mas-7-induced increase in PIP-PLC in vivo required a factor that was
      lost from the membrane during isolation.

PMID- 7716247
TI  - Cloning and expression analysis of the cytosolic NADP(+)-dependent isocitrate
      dehydrogenase from potato. Implications for nitrogen metabolism.
AB  - A full-length cDNA (icdh-1) encoding a cytosolic NADP(+)-dependent isocitrate
      dehydrogenase (ICDH-1) from potato (Solanum tuberosum L.) has been isolated.
      Analysis of the deduced protein sequence revealed considerable homologies with
      the corresponding proteins from other eukaryotes such as tobacco, alfalfa,
      soybean, cattle, pig, and yeast. The gene was transcribed in all tissues tested,
      with the highest amount of icdh-1 transcript being found in green tissues, in
      flowers, and in roots. In leaves, enzyme activities were dependent on the age,
      with fully mature leaves showing the highest level of RNA expression and enzyme
      activity. This observation may indicate that NADP(+)-dependent ICDH is not only
      involved in amino acid biosynthesis via the glutamine synthetase/glutamine
      oxoglutarate aminotransferase cycle but also in cycling, redistribution, and
      export of amino acids. The latter assumption has been strengthened by our finding
      of a preferential expression of NADP(+)-dependent ICDH in leaf veins. Under in
      vivo conditions, the expression pattern paralleled the enzyme activity,
      indicating coarse control on the RNA level. Experiments carried out with detached
      leaves revealed an influence of light, nitrate, and sucrose on icdh-1 transcript
      levels and in some cases also on NADP(+)-dependent ICDH activity. In darkness,
      nitrate or sucrose induced icdh-1 mRNA expression. Leaves kept under starvation
      conditions exhibited a decrease of their protein content, whereas icdh-1
      expression and ICDH activity increased significantly.

PMID- 7716248
TI  - Functional implications of structure-based sequence alignment of proteins in the
      extracellular pectate lyase superfamily.
AB  - Pectate lyases are plant virulence factors that degrade the pectate component of
      the plant cell wall. The enzymes share considerable sequence homology with plant
      pollen and style proteins, suggesting a shared structural topology and possibly
      functional relationships as well. The three-dimensional structures of two Erwinia
      chrysanthemi pectate lyases, C and E, have been superimposed and the structurally
      conserved amino acids have been identified. There are 232 amino acids that
      superimpose with a root-mean-square deviation of 3 A or less. These amino acids
      have been used to correct the primary sequence alignment derived from evolution
      based techniques. Subsequently, multiple alignment techniques have allowed the
      realignment of other extracellular pectate lyases as well as all sequence
      homologs, including pectin lyases and the plant pollen and style proteins. The
      new multiple sequence alignment reveals amino acids likely to participate in the
      parallel beta helix motif, those involved in binding Ca2+, and those invariant
      amino acids with potential catalytic properties. The latter amino acids cluster
      in two well-separated regions on the pectate lyase structures, suggesting two
      distinct enzymatic functions for extracellular pectate lyases and their sequence
      homologs.

PMID- 7716250
TI  - New ways to look at fitness.
AB  - Many authors have argued that the core of evolutionary biology as represented by
      the catchphrase 'The fittest survive' is tautological. Concerning the fitness
      concept of population genetics it is easy to rebut this charge by a proper
      explication of the term 'survival'. In biology and in the philosophy of biology,
      various fitness concepts over and above that of population genetics have been
      elaborated. These concepts, which are called 'supervenient' by some philosophers,
      have a limited usefulness. On some interpretations they do lead to unacceptable
      tautologies and circular reasoning. The so-called propensity concept of fitness
      is problematic in this respect. If interpreted in a proper way, supervenient
      concepts appear not to allow the formulation of highly general explanations and
      theories; at best they reveal common patterns among diverse non-general
      explanations and theories. Philosophers cherishing supervenient fitness concepts
      are apparently motivated by a mistaken search for general theory. The fitness
      concept of population genetics may play a role in relatively general theories and
      explanations. Supervenient concepts cannot play such a role. They should rather
      help us recognize the value of natural history in biology.

PMID- 7716249
TI  - Nucleotide sequence and expression of the genes for the alpha and beta subunits
      of phycocyanin in Cyanidium caldarium.
AB  - The nucleotide sequence of the plastid-encoded operon containing genes for the
      alpha (cpcA) and beta (cpcB) subunits of phycocyanin in the unicellular red alga
      Cyanidium caldarium is described. cpcB is located 5' to cpcA and the two genes
      are separated by a 102-bp spacer region. The transcription start site of cpcBA
      was mapped to 80 bp upstream of the ATG initiation codon of cpcB. Promoter-like
      elements similar to the -10 (TATAAT) and -35 (TTGACA) consensus promoters in
      bacteria were found 6 and 31 bp upstream of the transcription initiation site.
      Northern blotting revealed an abundant 1.3-kb cpcBA transcript in illuminated
      cells, but this transcript was undetectable in dark-grown cells. Expression
      levels of cpcBA in cells incubated with 10(-6) M heme in the dark were similar to
      those in cells illuminated for 24 h. Cells illuminated with 150 microM gabaculine
      (an inhibitor of delta-aminolevulinate synthesis) or 10 mM levulinic acid (an
      inhibitor of delta-aminolevulinate dehydrase) lacked detectable cpcBA
      transcripts. In cells illuminated with 200 microM N-methyl-mesoporphyrin IX (an
      inhibitor of ferrocheletase), inhibition of cpcBA expression and phycocyanin
      synthesis was similar. These results provide strong evidence that light induction
      of the cpcBA operon is dependent on synthesis of heme.

PMID- 7716251
TI  - Growth monitoring: the role of community health volunteers.
AB  - A community volunteer programme was initiated in rural Jamaica in May 1990. The
      main aim of the programme was to monitor the growth of children less than 36
      months of age through community health volunteers (CHVs) and improve their
      nutritional status. At the end of the second year the programme was evaluated to
      determine its effectiveness. The results of the evaluation indicated that almost
      all (95.6%) of the children were covered by the CHVs. In addition the
      participation rate was high (78.5%). However, only 50% of the children were
      adequately covered. Nonetheless, 81% of them gained adequate weight. Indeed,
      malnutrition levels declined by 34.5%. The annual cost per child per year for the
      total programme was fairly moderate (US$14.5) with growth monitoring accounting
      for nearly half (42.7). The results suggest that CHVs can play an important role
      in primary health care programmes in developing countries.

PMID- 7716252
TI  - A new method of evaluating selective school entry medicals.
AB  - There is an ongoing debate about the relative value of selective vs routine
      entrant medicals. This paper describes a districtwide study of entrant medicals
      using the tracer method to assess the prevalence and detection rates of problems
      at school entry. Overall 57% of school entrants were selected for a medical but
      there was a significant difference in selection rates in urban and rural schools.
      This selection rate is higher than that reported by other authors. There was a
      trend for tracer conditions to be more prevalent in urban areas although this was
      not statistically significant. Prevalence rates suggest that the method of
      selection successfully detected children with problems. The tracer methodology
      provided useful information for service planning without the collection of large
      amounts of data and has not, to our knowledge, been used before in community
      child health. We recommended this methodology to other districts as a simple and
      effective method of assessing selective entrant medicals.

PMID- 7716253
TI  - Improving the selection of children for health assessment at secondary transfer
      age: completing the audit cycle.
AB  - Whilst there have been many reported assessments of selective medicals at 5+
      school entry, there is a dearth of publications on the value of selected medical
      review at secondary transfer age. It was decided to evaluate this within the
      South Downs Health Trust. The team of child health doctors was asked to record
      data about children selected for medical review at secondary transfer age in
      1992. Differences in practice were discussed, protocols were introduced and the
      exercise repeated. Overall the second year showed no evident change with 9.5% of
      children selected from 2729 in 1992 and 9.6% selected from 2473 in 1993. However,
      analysis of individual schools showed significant changes which illustrated the
      improvements achieved and the areas of weakness remaining to be addressed.

PMID- 7716254
TI  - Ethnic group and alcohol consumption: the case of 15-16-year-olds in
      Leicestershire.
AB  - In recent years a number of research projects have reported on the level of
      alcohol use by young people. The research to date, however, has tended to
      overlook the ethnic origins of the young people as a factor associated with the
      level of alcohol use. Against this background, this paper reports findings on the
      use of alcohol by 15-16-year-olds in Leicestershire with specific reference to
      ethnic group. A survey of over 1000 young people revealed significant differences
      between ethnic groups in terms of their attitudes to alcohol consumption and the
      frequency of alcohol consumption. As expected, South Asians tended to hold less
      favourable attitudes to drinking alcohol than their White counterparts and
      reported a far lower frequency of alcohol consumption. The extent of the
      divergence between the two ethnic groups is detailed, revealing a stark contrast
      between the groups at age 15-16 years. Attitudes to alcohol consumption and
      reported frequency of alcohol consumption were also analysed in relation to the
      religion of the respondents. This analysis was undertaken to see if there were
      differences within the broader ethnic groups which would be disguised by
      aggregating the results under the headings of 'South Asian' and 'White'. Within
      the South Asian group, some differences in attitudes to the consumption of
      alcohol were found between Hindus, Sikhs and Muslims, with the Muslims exhibiting
      particular sensitivity to their religion's proscription of drinking alcohol.
      Despite this, the reported level of drinking by the Hindus and Sikhs was not much
      greater than that of the Muslims. The three groups tended to have a similar
      frequency of alcohol consumption which was markedly lower than that reported by
      the White 15-16-year-olds. The findings from the DART research have certain
      substantive and certain methodological implications in relation to
      epidemiological studies of alcohol consumption. Substantively, the findings
      reinforce the need to include ethnic group as a key factor and highlight the
      danger of aggregating the results from different ethnic groups. In the case of
      Leicestershire, the effect of ignoring the ethnic dimension would have been to
      underestimate significantly the extent of drinking among the White 15-16-year
      olds. Methodologically, the findings offer some support for the continued use of
      'South Asian' as an analytic category since the variations observed within the
      category were relatively minor, especially in comparison with results for the
      White 15-16-year-olds.

PMID- 7716255
TI  - Speech and language therapy: is it effective?
AB  - As part of a needs assessment of local speech and language therapy services, a
      review of the literature was carried out to examine the evidence for
      effectiveness of speech and language therapy. Purchasing authorities and general
      practice fundholders need to know whether what they are buying for their local
      population is effective, and whether the service is being provided in the most
      cost-effective way. This paper considers the published evidence and some of the
      limitations of the studies, and gives suggestions for purchasing speech and
      language therapy services based on current evidence. More evaluative work needs
      to be done to provide purchasers with the information necessary to decide which
      speech and language therapy services will result in real benefits for their
      population.

PMID- 7716256
TI  - Leading article--understanding and preventing violence: a review.
AB  - In England and Wales the level of violence is lower than that of many other
      countries, including notably the major epidemic of violence in the United States
      of America. However, even in England and Wales, violent crimes are increasing
      steadily and unless this is treated as a major public health issue we may well go
      down the same road as the USA. This article reviews the evidence, much of which
      is from America, in the hope that it will stimulate the development of strategies
      to reduce the level of violence in our society. Many of the underlying factors
      are known, although research is still needed to disentangle the effects of each
      of the many variables. At present too little of such research is based in the UK.
      The Government's Chief Medical Officer has identified the health of adolescents
      as one of four new areas of particular importance requiring broader discussion in
      the coming year and comments that 'adolescence is a crucial period during which
      lifestyles, values and attitudes are established'. This paper identifies the main
      risk factors which tend to breed antisocial behaviour in adolescents in so far as
      they relate to violence.

PMID- 7716257
TI  - A one-year community study of under-fives in rural Ethiopia: patterns of
      morbidity and public health risk factors.
AB  - A prospective weekly home surveillance study was undertaken to determine
      morbidity patterns within the Butajira Rural Health project in central Ethiopia.
      Overall prevalence of illness was 5.8% in 1216 person-years observed among rural
      Ethiopian children aged under 5 years. Acute respiratory infections (ARI)
      (prevalence 2.8%) and acute diarrhoea (2.4%) were the commonest conditions.
      Episodes of illness were distributed unequally among children, with a mean of
      2.34 episodes per child. These included an average of 1.13 episodes of ARI (of
      which 0.16 had lower respiratory symptoms [ALRI]) and 1.17 episodes of acute
      diarrhoea. Sanitation factors were the principal risks for gastroenteritis, while
      living in rural areas predisposed children to ARI. Parental factors such as
      illiteracy were also linked to morbidity.

PMID- 7716258
TI  - Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters
      released from peripheral endings of sensory nerves.

PMID- 7716259
TI  - Patient preference for high or low dose rate brachytherapy in carcinoma of the
      cervix.
AB  - High and low dose rate are two competing methods of brachytherapy. Existing data
      do not support choosing one method over the other for treating carcinoma of the
      uterine cervix. Arguments include clinical efficacy, monetary cost, radiation
      safety, and patient preference. There are no published data on patient
      preference. We developed a questionnaire to elicit patient preference and to
      measure its strength. Subjects received descriptions of both treatment options
      and their probable outcomes. We elicited preference for one low or three high
      dose rate fractions, and for two low or five high dose rate fractions, assuming
      both methods to be isoeffective. Strength of initial preference was measured by
      asking subjects how much of a change, in either the changes for cure or the
      chances for toxicity, would make them change preference. The questionnaire was
      completed by female staff at our centre (n = 90), by a group of previously
      treated patients (n = 18), and by a group of newly diagnosed patients (n = 20).
      When both methods were assumed to be isoeffective, only 34% of the 38 patients
      preferred three fractions of high dose rate to one fraction of low dose rate.
      However, when high dose rate was assumed to be 2% more curative, or 6% less
      toxic, a simple majority of 50% then said they would prefer high dose rate. Both
      preference and strength of preference for low dose rate were significantly
      associated with a greater travelling distance for treatments. Age, marital
      status, family structure, education, employment, and family income were not
      associated. In summary, a majority of our patients preferred low dose rate
      brachytherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716260
TI  - Brachytherapy for lower lip epidermoid cancer: tumoral and treatment factors
      influencing recurrences and complications.
AB  - From 1972 to 1991, 237 patients with squamous cell carcinoma of the lower lip
      were treated by exclusive LDR brachytherapy (192Ir). There were 158 T1, 61 T2, 17
      T3 and 1 T4 with 231 N0, 3 N1 and 3 N2 patients. The actuarial values at 5 years
      for local and regional controls, overall and specific survivals were 95%, 91%,
      74% and 91%. Salvage treatment increased local control up to 99% and regional
      control to 94%. No heterolabial recurrence has been observed since the entire lip
      is treated, even for small tumors. The regional control depends closely on the
      thickness of the labial tumor (> or = 1 cm, p < 0.0001). The healing of treatment
      induced mucositis is sometimes delayed for thick tumors (> or = 1 cm, p = 0.015).
      Late complications are not related to tumoral thickness but to the treated
      thickness (> 1.4 cm, p = 0.018) and particularly to the thickness of normal
      tissue included in the 85% isodose (treated thickness - tumoral thickness > 0.4
      cm, p = 0.025). The use of a leaded protection and low linear radioactivity wires
      (< 2 mCi/cm, < 8.6 muGy/h.m2/cm) especially for large target volumes is required
      to lessen late complications. Based on this review, we advocate exclusive
      brachytherapy for small and intermediate tumors, with elective bilateral
      submaxillary and submental dissection for thick, high grade or commissure tumors.
      Simple recommendations are made to assure quality of the brachytherapy treatment.

PMID- 7716261
TI  - Differential radiosensitising effect of the scid mutation among tissues, studied
      using high and low dose rates: implications for prognostic indicators in
      radiotherapy.
AB  - To assess whether radiation-sensitive or radiation-resistant individuals should
      in principle be predicted equally well using different cell types, the effect of
      the scid mutation on the radiosensitivity of colony-forming cells in different
      murine tissues was assessed using high and low dose-rates. At high dose-rate, the
      amount of radiosensitization due to the scid mutation was greater in epithelial
      cells of the intestine and the kidney than in haemopoietic and fibroblastoid
      cells in the bone marrow, when expressed as a dose reduction factor. However,
      this greater radiosensitization in intestine and kidney did not translate into
      bigger differences in SF2 (surviving fraction at 2 Gy) or SF3.5. This was because
      of the greater inherent radioresistance of the epithelial cells compared with the
      marrow cells, resulting in smaller changes in cell survival from a given dose.
      Reductions in cell survival due to the mutation increased with increasing dose as
      expected at high dose rate. The changes in SF2 and SF3.5 due to the scid mutation
      were not significantly increased by using low dose-rates, because of the tendency
      for the presence of some low dose-rate sparing in the scid cells as well as the
      marked amount observed in the wild-type cells. The implications for predictive
      testing in radiotherapy are that for genetic defects resulting in the same type
      of radiosensitization phenomenon shown here for scid cells, radiosensitive or
      radioresistant cell types may still give similar differentials in response due to
      the mutation when SF2 is used as an endpoint.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716262
TI  - The effect of radiation on G2 blocks, cyclin B expression and cdc2 expression in
      human squamous carcinoma cell lines with different radiosensitivities.
AB  - The purpose of the present study was to investigate the role of cyclin B and cdc2
      in the G2 delay and to test whether the magnitude of the G2 delay correlated with
      sensitivity to ionizing radiation in two human cell lines. Cell cycle delays were
      measured by flow cytometry after pulse labeling with bromodeoxyuridine, and
      expression of cell cycle control genes were measured in Western blots in
      radiosensitive SCC61 and radioresistant SQ20B cell lines. Flow cytometry data
      demonstrated that the duration of the G2 arrest was dose dependent in both cell
      lines, amounting to approximately 1.1 h/Gy. No difference was found between the
      cell lines in the length of the G2 block. Radiation exposure did not result in a
      decrease of cyclin B. Cyclin B protein levels in both asynchronous and
      synchronized populations in fact showed a dose dependent increase, concomitant
      with the rise in the fraction of cells in G2/M. Similarly, the cdc2 protein
      levels did not decrease after irradiation. However, it was found that the levels
      of hyperphosphorylated, and therefore inactive, kinase were significantly higher
      in irradiated cells than in unirradiated cells. The accumulation of this
      hyperphosphorylated form correlated with the arrest of cells in the G2 phase.
      Finally, immunocytochemical staining of cyclin B revealed an increase of this
      protein in the cytoplasm after irradiation and a decrease in nuclear staining.
      This differential localization could possibly account for the reduced nuclear
      phosphorylation of cdc2 kinase leading to the G2 arrest.

PMID- 7716263
TI  - The relationship between cellular radiation sensitivity and tissue response may
      provide the basis for individualising radiotherapy schedules.
AB  - There is a wide variation in normal tissue reactions to radiotherapy and in many
      situations the severity of these reactions limits radiotherapy dose. Clinical
      fractionation studies carried out in Gothenburg have demonstrated that a large
      part of the spectrum of normal tissue reactions is due to differences in
      individual normal tissue sensitivity. If this variation in normal tissue
      reactions is due to differences in intrinsic cellular radiosensitivity, it should
      be possible to predict tissue response based on measurement of cellular
      sensitivity. Here we report the initial results of a study aimed at establishing
      whether a direct relationship exists between cellular radiosensitivity and tissue
      response. Ten fibroblasts strains, including four duplicates, were established
      from a group of patients in the Gothenburg fractionation trials who had received
      radiotherapy following mastectomy. Skin doses were measured and both acute and
      late skin changes were observed following radiotherapy. Right and left
      parasternal areas were treated with different dose fractionation schedules.
      Clonogenic assays were used to assess intrinsic cellular radiosensitivity, and
      all experiments were carried out without prior knowledge of the clinical
      response, or which strains were duplicates. Irradiation was carried out using
      60Co gamma-rays at high dose-rate (HDR) of 1-2 Gy/min and low dose-rate (LDR) of
      1 cGy/min. A spectrum of sensitivity was seen, with SF2 values of 0.17-0.28 at
      HDR and 0.25-0.34 at LDR, and values of D0.01 of 5.07-6.38 Gy at HDR and 6.43
      8.12 Gy at LDR. Comparison of the in vitro results with the clinical normal
      tissue effects shows a correlation between cellular sensitivity and late tissue
      reactions, which is highly significant with p = 0.02. A correlation between
      cellular sensitivity and acute effects was noted in the left-sided parasternal
      fields, but not the right. This is thought to be coincidental, and without
      biological significance. Our results suggest that cellular sensitivity might form
      the basis for the development of an assay system capable of predicting late
      normal tissue effects to curative radiotherapy, which might allow dose escalation
      in some patients. Increased local control and cure, with unchanged or improved
      normal tissue complications, could result from such individualised radiotherapy
      prescriptions.

PMID- 7716264
TI  - A comparison of proton and megavoltage X-ray treatment planning for prostate
      cancer.
AB  - Conformal photon and proton therapy plans for prostate cancer have been compared
      in an attempt to quantify the potential advantages of using protons. Two X-ray
      plans (3-field, 6-field) and a 2-field proton plan were made and compared for
      each of 20 T3 prostate patients with the aid of the 3D planning system VOXELPLAN.
      Dose distributions were analysed in terms of dose-volume histograms (DVH). Tumour
      control probability (TCP) and normal tissue complication probability (NTCP) were
      computed using our own and the Lyman-Kutcher-Burman models, respectively. The
      study shows that on average the proton technique results in the best dose
      distribution, giving the lowest rectal complication probability, and also that
      the 3-field X-ray technique is more effective than the 6-field X-ray technique in
      sparing the rectum. At 5% rectal NTCP, the predicted proton average TCP for the
      20 patients is 2% (in absolute terms) greater than that obtained using 3-field X
      ray therapy. For 7 of the patients the gain in TCP is more than 3%. For the same
      rectal NTCP as the 3-field X-ray plan with a 64 Gy mean target dose, the use of
      protons increases the TCP by 2% on average, but for 5 of the patients the
      increases are greater than 4%. The result is in general positive towards the use
      of protons but a few patients do not benefit from it and this indicates the
      importance of patient selection for maximum clinical benefit.

PMID- 7716265
TI  - Treatment of primary squamous cell carcinoma of the trachea: the role of
      radiation therapy.
AB  - Eleven patients with SCC of the trachea were treated (ten primarily, one
      postoperatively) with megavolt irradiation (four in combination with
      brachytherapy). A median survival of 31 and a median disease free survival of 7.5
      months was observed. Factors favourable for survival were the achievement of
      complete remission, the absence of mediastinal lymphnode involvement, and the use
      of additional brachytherapy.

PMID- 7716266
TI  - Hyperfractionated radiotherapy for brain stem tumours in children.
AB  - From 1988 to 1992 in the Centre of Oncology, Warsaw, 42 children with brain stem
      tumours were treated with hyperfractionated radiotherapy (HFRT). Two-year
      survival in nine (27%) patients was obtained. The HFRT treated group was compared
      with the historical, conventionally irradiated group with the same diagnosis. The
      hyperfractionated radiotherapy was well tolerated, but did not improve survival
      rate in comparison with conventionally treated group.

PMID- 7716267
TI  - The effect of the perflubron emulsion Oxygent on the calibration characteristics
      of polarographic oxygen electrodes.
AB  - The perfluorocarbon emulsion Oxygent improves normal tissue oxygenation. A
      clinical trial is planned to evaluate this effect in tumors. Polarographic oxygen
      electrodes were calibrated in solutions of saline +/- perflubron to assess
      whether Oxygent influenced probe behavior. Calibrations were linear under both
      conditions. There were no major differences in estimated oxygen tensions.

PMID- 7716268
TI  - The prognostic significance of hyperploid cells in squamous carcinoma of the
      uterine cervix treated with radiotherapy.
AB  - Smears were obtained from patients undergoing radiotherapy for Stage I-IV
      squamous cell carcinoma of the cervix. The presence of cells with large or
      multiple nuclei in smears taken during or not more than 1 month following therapy
      was found to be associated with a significantly increased risk of early relapse.

PMID- 7716269
TI  - The pedicled omentoplasty, a simple and effective surgical technique to acquire a
      safe pelvic radiation field; theoretical and practical aspects.
AB  - A substantial number of patients need radiotherapy after surgery for pelvic
      malignancy. Approximately 15% of them will experience radiation enteritis. After
      omentoplasty, reduction of irradiated bowel volume may be obtained. We evaluated
      the pedicled omentoplasty during gynaecologic surgery as a technique to improve
      safe irradiation of the pelvic region.

PMID- 7716270
TI  - Angiotensin II stabilizes a multimeric type 2 (AT2) receptor complex in murine
      neuroblastoma N1E-115 cells.
AB  - Previous work has demonstrated that crosslinking of [125I]AngII to CHAPS
      solubilized angiotensin Type 2 receptors (AT2) in N1E-115 neuroblastoma cells
      identifies two radiolabeled proteins of 110 and 66 kDa. Similarly, affinity
      purification of AT2 receptors using AngII yields two proteins of 110 and 66 kDa.
      In the present study, anti-AT2 receptor antisera were used to examine the
      relationship between these two proteins. Agonist treatment (AngII) of intact
      cells increased the 110 kDa band while decreasing the 66 kDa protein. In intact
      or solubilized membranes, the ratio of 110 kDa/66 kDa proteins was significantly
      higher in the presence of an agonist and substantially lower with the antagonist
      Sar1,Ile8-AngII, suggesting that AngII stabilizes a large 110 kDa multimeric
      complex that may include the 66 kDa protein. To directly examine this hypothesis,
      anti-AT2 antisera were further purified against either the 110 or 66 kDa
      proteins. Both purified antibodies displayed crossreactivity with the two
      proteins. Moreover, when harshly reduced and denatured, the 110 kDa protein
      released a prominent immunoreactive 66 kDa protein, as well as other smaller
      proteins. Collectively, these results suggest that the 110 kDa protein consists,
      in part, of the 66 kDa protein and, as such, that an AT2 receptor subtype may
      exist as a multimeric complex that is stabilized by agonist occupancy.

PMID- 7716271
TI  - Differential effects of pertussis toxin on body temperature changes induced by
      neuropeptide Y and NPY2-36.
AB  - Many effects of NPY have been attributed to a decrease in the activity of
      adenylate cyclase. Pre-treatment with pertussis toxin (PTx) has been shown to
      inhibit many pharmacological effects of NPY including increased feeding following
      administration in the paraventricular nucleus (PVN). In the present study, we
      examined the influence of PTx pretreatment on the effects of NPY on body
      temperature following administration in the preoptic area (POA), a region which
      seems to be the most sensitive to the effects of the peptide on body temperature.
      The effects of the same pre-treatment on the action of NPY2-36 was also studied
      since we have found previously that this fragment produced opposite effects on
      body temperature to that of NPY when injected in the POA. PTx was administered 3
      days prior to the injection of NPY or NPY2-36. Results indicate that the
      hypothermic effect of NPY produced in the POA was blocked by PTx whereas the
      hyperthermic effect of NPY2-36 was not affected. These results are important as
      they provide evidence that, in the POA at least, the receptors mediating the
      hypothermic effect of NPY might be biochemically different from those mediating
      the hyperthermic effect of NPY2-36.

PMID- 7716272
TI  - Gonadotropin-releasing hormones in microdissected brain regions of an amphibian:
      concentration and anatomical distribution of immunoreactive mammalian GnRH and
      chicken GnRH II.
AB  - Mammalian and chicken II gonadotropin-releasing hormones (mGnRH, cGnRH II) were
      extracted from 350 microns diameter punches from brains of a urodele amphibian,
      Taricha granulosa, and measured by means of radioimmunoassay (RIA) with specific
      antisera. Measurable quantities of both peptides were found in the lateral
      pallium, the subpallium (along the course of the nervus terminalis), the preoptic
      area, habenula, optic tectum, infundibulum, paraventricular organ/posterior
      tubercle of the caudal diencephalon, medulla, and cerebrospinal fluid. Highest
      concentrations of both peptides were in the preoptic area and infundibulum,
      suggesting a role in gonadotropin release. In most extrahypothalamic regions,
      cGnRH II concentrations exceeded those of mGnRH, suggesting that cGnRH II may
      function as a neurotransmitter in many sites, perhaps to control reproductive
      behaviors. Results are largely consistent with immunocytochemical (ICC) analyses,
      except that RIA revealed small amounts of both peptides not found by ICC in some
      areas of the brain. Results from this microdissection/RIA study and prior ICC
      studies in amphibians support the conclusions that GnRH cell bodies in the
      terminal nerve and preoptic area, which project mainly to the median eminence and
      habenula, express mGnRH, and that GnRH cell bodies in the caudal diencephalon,
      which project widely throughout the CNS, express cGnRH II. Comparative data
      support the view that cGnRH II, and the neural systems in which it is expressed,
      evolved early in vertebrate phylogeny and have been highly conserved.

PMID- 7716273
TI  - Properties of the VIP-PACAP type II receptor stably expressed in CHO cells.
AB  - The VIP receptor cloned from rat lung (VIP1 receptor from the group of the PACAP
      VIP type II receptors) was inserted into a mammalian expression vector and stably
      transfected into Chinese hamster ovary cells (CHO). Two clones were selected,
      expressing respectively a high (850 +/- 50 fmol/mg protein, for clone 3) and a
      low (100 +/- 30 fmol/mg protein for clone 16) number of receptors. Both clones
      had the same apparent Kd value of binding for VIP and related peptides. The
      receptor expressed had the same binding properties as the natural VIP receptor,
      judged from the relative potency of VIP and PACAP analogues and fragments. The
      EC50 value of adenylate cyclase activation were 3 to 10 fold lower in clone 3
      than in 16. The values observed in clone 16 were closer to the binding Kd values.
      The differences between the two clones were explained by the existence of spare
      receptors in clone 3, since: (a) the relative efficacy of some fragments were
      lower in clone 16 than in clone 3; (b) pretreatment of the cells with VIP reduced
      the number of receptors in both clones and increased the EC50 value for VIP in
      clone 3 but decreased peptide efficacy in clone 16 without significant change of
      the EC50 value.

PMID- 7716274
TI  - Chronotropic cardiac effects of NPY in conscious dogs: interactions with the
      autonomic nervous system and putative NPY receptors.
AB  - The chronotropic cardiac effects of neuropeptide Y (NPY) were studied in the
      conscious dog with chronic atrioventricular block. NPY (0.2-5 micrograms/kg i.v.)
      produced no effect on atrial cycle length (ACL), and increased ventricular cycle
      length (VCL) and mean arterial blood pressure (MBP). After atropine, NPY produced
      no effect on ACL and increased MBP. At 0.2 microgram/kg, it shortened VCL,
      whereas at 1 and 5 micrograms/kg, it lengthened this parameter. After pindolol,
      NPY produced no effect on ACL, shortened VCL and increased MBP. These results
      indicate that in the conscious dog, NPY (0.2-5 microgram/kg i.v.) does not exert
      any chronotropic effect on the sinoatrial node, most likely because of
      competition between opposite chronotropic effects and/or absence of specific NPY
      receptors in the sinoatrial node. They also suggest that the ventricular
      bradycardic effects produced by NPY result mainly from a reflex withdrawal of
      beta-adrenergic tone and that its ventricular tachycardic effects result from a
      direct action of NPY on specific receptors located in the His bundle.

PMID- 7716275
TI  - Changes in rat atrial ANF granules induced by hindlimb suspension.
AB  - It is well known that the heart releases a factor called ANF (atrial natriuretic
      factor) or ANP (atrial natriuretic peptide) capable of inducing rapid diuretic
      and natriuretic actions. This factor is stored in secretory granules mainly
      located in myocytes in both atria. The main secretory stimulus is the distention
      of the atrial cavity resulting, for example, from enhanced venous return.
      However, the cellular events which occur after the stimulation remain to be
      clarified. The aim of this investigation was to study the intra-cellular events
      preceding the ANF release, using the rat hindlimb suspension as model of
      stimulation. In this model, Wistar rats were placed in a 30 degrees anti
      orthostatic position and a blood shift towards the heart was obtained. Different
      durations (1/4 h, 1/2 h, 3/4 h, 1 h, 2 h and 6 h) were studied. The ANF plasma
      level was investigated by Radio Immuno Assay and granule immunoreactivity was
      measured by counting gold particles on micrographs. The ANF plasma level was
      significantly increased (+60%) after 1 h of suspension. The response was
      transient and then decreased to basal values. Morphological criteria established
      at the beginning of this study, and measured throughout the experiment, were
      found transiently modified after suspension. The surface of the perinuclear area
      was transitory enlarged by 36% 30 min after suspension. Moreover, in the same
      time immunoreactivity of the secretory granules was enhanced without changes in
      granule size. These results suggest an increase in the ANF synthesis and storage
      in the granules during the stimulation. However, the cellular regulatory
      mechanism of the ANF synthesis which could explain the transitory aspect of these
      events, requires further investigation.

PMID- 7716276
TI  - Quantitative modifications induced by angiotensin II on rat bile secretion.
AB  - Angiotensin II (ANG II) effects on bile secretion were studied in the rat. ANG II
      (0.1 microgram/kg) was injected into the jugular vein every 30 min and bile
      samples of 30 min were collected for 120 min. Blood arterial and portal venous
      pressures were simultaneously recorded before and after the administration of ANG
      II. Results showed that ANG II decreased bile flow and the excretion of sodium,
      potassium, chloride and bile acids whereas it increased pH, bile osmolality and
      the excretion rate of bicarbonate and calcium. ANG II also led to a rapid
      increase in mean arterial pressure as well as portal venous pressure which
      reverted to control values within 1 min. The present results suggest that ANG II
      may modulate bile flow and the excretion rate of the different biliary
      constituents. We have previously investigated atrial natriuretic factor effects
      on bile secretion and although the atrial factor antagonizes most of ANG II
      biological actions, unexpectedly, ANG II effects on bile secretion were not
      opposite to those of atrial natriuretic peptide. The modifications induced by ANG
      II on bile secretion may play an important role in pathophysiological conditions
      such as hypertensive states with increased ANG II circulating levels.

PMID- 7716277
TI  - Interactions between NPY and its receptor: assessment using ant-NPY antibodies.
AB  - The present data show that monoclonal antibodies (NPY02, NPY03, NPY04, NPY05)
      directed against 4 distinct epitopes on NPY may have different actions on NPY
      binding and NPY-induced cellular responses. NPY02 and NPY05 recognize the 11-24
      and 32-36 amidated form of NPY, respectively. These 2 antibodies block the
      binding of NPY to its receptor as well as the NPY-induced inhibition of cAMP
      accumulation caused in SK-N-MC cells by forskolin. NPY02 and NPY05 have also an
      inhibitory action on NPY-induced contraction of rabbit femoral arteries. NPY03
      and NPY04 are directed against the 27-34 and 1-12 part of NPY, respectively.
      NPY03 and NPY04 inhibit the binding of NPY only at very high concentrations and
      have a weak effect on cAMP response to NPY. NPY02 and NPY05 might provide useful
      tools to study the effect of NPY in cellular systems and organ preparations.

PMID- 7716278
TI  - Effects of three fragments of parathyroid hormone on calcium channel currents in
      neonatal rat ventricular cells.
AB  - The effects of different fragments of bovine parathyroid hormone, bPTH-(1-34),
      bPTH-(1-84) and bPTH-(3-34), on two types of calcium channel currents in neonatal
      rat ventricular cells were compared in the present study. bPTH-(1-34) increased
      the amplitude of L channel currents, but not of the T channel currents. This
      effect of bPTH-(1-34) was sustained after a complete washout of the peptide from
      the bath. The intact PTH molecule, bPTH-(1-84), also increased L channel currents
      but not affecting T channel currents. While bPTH-(3-34) did not affect the
      amplitudes of either L or T channel currents by itself, pretreatment of cells
      with bPTH-(3-34) abolished the effects of both bPTH-(1-34) and bPTH-(1-84) on L
      channel currents. Moreover, the kinetics of L channel currents in the presence of
      bPTH-(1-34) or bPTH-(3-34) were different. bPTH-(1-34) increased the time
      constant of activation, but not of inactivation, of L channel currents from 1.8
      to 2.5 ms (P < 0.05). In contrast, bPTH-(3-34) decreased the time constant of
      inactivation, but not of activation, of L channel currents from 159 to 117 ms (P
      < 0.05). These results indicate that different fragments of PTH exert different
      effects on the amplitudes or kinetics of cardiac calcium channel currents.

PMID- 7716279
TI  - Identification of chicken GnRH II in brains of metatherian and early-evolved
      eutherian species of mammals.
AB  - Two molecular forms of GnRH (chicken GnRH II and a second variant) are present in
      the brains of species from all the major vertebrate groups. In mammals, two forms
      are present in metatherian species and early-evolved eutherian species, but
      chicken GnRH II has not been identified in more advanced eutherian species. We
      investigated the nature of GnRH molecular forms in several early-evolved
      mammalian species, using high performance liquid chromatography and
      radioimmunoassay with specific GnRH antisera. These chromatographic and
      immunological data indicate that in the brains of a metatherian species (possum,
      Trichosurus vulpecula) and in two early-evolved eutherian species (order
      Insectivora: musk shrew, Suncus murinus and mole, Chrysochloris asiatica), both
      mammalian and chicken II GnRHs are present, while in another relatively early
      evolved eutherian species (order Chiroptera: bat, Miniopterus schreibersii) only
      mammalian GnRH is present. In the adult possum and mole brains the proportion of
      chicken GnRH II was lower than that of mammalian GnRH, while in the musk shrew
      brain chicken GnRH II predominated. A peptide likely to be mammalian proGnRH was
      detected in the brains of the three eutherian species (musk shrew, mole, and
      bat). These findings suggest that metatherian and primitive eutherian species of
      mammals continue to express chicken GnRH II as in the vast majority of
      nonmammalian vertebrates, while the peptide is apparently not expressed in modern
      placental mammalian species. The functional significance of chicken GnRH II is
      not yet clear, but there are indications that it has a neurotransmitter or
      neuromodulator role in addition to that of regulating pituitary hormone release
      in certain vertebrate species.

PMID- 7716280
TI  - The effect of pentagastrin on the somatostatin receptor/effector system in rat
      pancreatic acinar membranes.
AB  - An intraperitoneal (i.p.) injection of pentagastrin (250 micrograms/kg, three
      times daily) for 1 week increased somatostatin like-immunoreactivity (SSLI)
      content in the pancreas and the number of somatostatin (SS) receptors in
      pancreatic acinar membranes without influencing their apparent affinity as
      compared with control animals. No significant differences were seen in basal or
      forskolin (FK)-stimulated adenylate cyclase (AC) enzyme activities in the control
      and pentagastrin treated rats. In spite of the increase in the number of SS
      receptors, SS caused a significantly lower inhibition in AC activity in these
      membranes. This finding is related to the fact that the stable GTP analogue, 5'
      guanylylimidodiphosphate (Gpp[NH]p) was a much less potent inhibitor of binding
      in the pancreatic acinar cell membranes from pentagastrin-treated animals than in
      those from controls. In addition the ability of Gpp(NH)p to inhibit FK-stimulated
      AC activity was also decreased in pancreatic acinar cell membranes from
      pentagastrin-treated rats. Pretreatment with proglumide, (20 mg/kg i.p.) a
      gastrin/cholecystokinin (CCK) receptor antagonist, prevented the pentagastrin
      induced changes in SS level and binding as well as the inhibitory effect of SS on
      AC activity in pancreatic acinar cell membranes. Proglumide alone had no
      observable effect on the somatostatinergic system. These data suggest a SS
      receptor/G protein uncoupling as a result of binding of pentagastrin to gastrin
      receptors present in pancreatic acinar cell membranes.

PMID- 7716281
TI  - Differential actions of lamprey peptide methionine-tyrosine at Y1 and Y2
      neuropeptide Y receptors.
AB  - Peptide methionine-tyrosine (PMY), a peptide of the neuropeptide Y (NPY)
      superfamily isolated from the brain and intestine of the sea lamprey, had the
      same maximum effect but was 11-fold less potent than pig NPY in inhibiting field
      stimulated contraction of the rat vas deferens, an effect mediated through the Y2
      receptor. In contrast, PMY produced a 9-fold greater maximum effect but was 3
      fold less potent than pig NPY in contracting the guinea pig mesenteric artery, an
      effect mediated through the Y1 receptor. Molecular modelling has suggested that
      the conformation of PMY is appreciably different from NPY only in the beta-turn
      region of the molecule (residues 9-14). Our data suggest, therefore, that
      modifications in this region of NPY may useful in the design of receptor
      selective analogs.

PMID- 7716282
TI  - The in vitro intestinal absorption of enterostatin is limited by brush-border
      membrane peptidases.
AB  - The intestinal metabolism and absorption of enterostatin was studied using brush
      border membrane vesicles and an in vitro model of intestinal segments from rabbit
      ileum mounted in Sweetana-Grass diffusion chamber. Hydrolysis of enterostatin was
      observed with both epithelial sheets and brush-border membranes. The main
      metabolite was found to be des-arginine-enterostatin. Dipeptidylpeptidase IV was
      found to play a minor role in enterostatin degradation, whereas carboxypeptidase
      P activity accounted for the initial step of peptide hydrolysis. More than 50% of
      the amount of enterostatin added to the mucosal compartment of the Sweetana-Grass
      diffusion chamber was degraded after 30 min. Enterostatin was mainly absorbed as
      degradation products but a small transepithelial passage of des-arginine
      enterostatin and immunoreactive enterostatin was also detected. Although
      immunoreactive enterostatin exhibits a low apparent permeability coefficient in
      rabbit ileum, the luminal production of this peptide may be of physiological
      importance in the control of appetite.

PMID- 7716283
TI  - Receptor-independent mechanisms are involved in the priming of neutrophil's
      oxidase by vasoactive intestinal peptide.
AB  - Vasoactive intestinal peptide (VIP) primed the respiratory burst of human
      neutrophils induced by phorbol myristate acetate (PMA) and by the chemotactic
      peptide N-formyl-Met-Leu-Phe (fMLP). The sigmoidal-shaped curve of the priming
      effect of VIP differs for both agonist since the Hill coefficient was close to
      three in the case of neutrophil activation by fMLP whereas the corresponding
      value for PMA was close to one. The priming effect of VIP was enhanced when
      neutrophils were stimulated by FMLP in the presence of sphinganine, a protein
      kinase C inhibitor, at concentrations which almost abolished the response to PMA.
      VIP failed to increase resting cytosolic free calcium and to modify the transient
      increase in [Ca2+]i induced by fMLP. The described results point out that the
      mechanism of the priming of neutrophils by VIP is also independent of calcium and
      protein kinase C. The absence of VIP receptors in plasma membrane of neutrophils
      suggests that a receptor-independent mechanism modulates the agonist-triggered
      signaling pathway. The priming of neutrophils by VIP can not be considered as a
      pharmacological effect, as may be deduced from the required VIP concentration; it
      should be rather considered that the enhancement of the formation of reactive
      oxygen metabolites by VIP may be interesting in the understanding of the
      neuroimmune axis.

PMID- 7716284
TI  - Distribution and chemical phenotypes of neuroendocrine cells in the human anal
      canal.
AB  - The presence, morphology and distribution of anal neuroendocrine cells were
      investigated with a panel of antisera and antibodies for neural markers, biogenic
      amines, and neuropeptides by the sensitive streptavidin-biotin-peroxidase
      immunocytochemistry, and coexistence patterns of neurochemically characterized
      neuroendocrine cells were examined by double immunofluorescence cytochemistry. In
      the colorectal zone, endocrine-like cells were immunoreactive for chromogranin A
      (CGA), serotonin (5-HT), pancreastatin (PST), peptide tyrosine tyrosine (PYY),
      glucagon-like peptide-1 (GLP-1), and somatostatin (SOM). Coexistence patterns of
      endocrine-like cell phenotypes with CGA and GLP-1 were heterogeneous. In the anal
      transitional zone (ATZ), endocrine-like cells were immunoreactive for CGA, 5-HT
      and PST. Furthermore, six new phenotypes of endocrine-like cells were
      characterized by their immunoreactivity for PYY, GLP-1, protein gene product 9.5
      (PGP), calcitonin gene-related peptide (CGRP), neurotensin (NT), and SOM. All
      endocrine-like cell types in the ATZ were immunoreactive for CGA. In the squamous
      zone and perianal skin, CGA-immunopositive Merkel cells were also immunoreactive
      for CGRP, PST, NT and PGP. Neuroendocrine cells in the anal canal exhibit
      epithelial zone-related diversities in their neurochemical phenotypes and
      coexistence patterns, which may indicate specific regulatory functions. In the
      epithelium of the ATZ, which is regarded as metaplastic, endocrine-like cells
      expressed phenotypes characteristic of the neuroendocrine cells of the colorectal
      zone and the squamous zones, indicating a possible metaplastic origin of these
      cells.

PMID- 7716286
TI  - [A centenary of the discovery of X-rays].

PMID- 7716285
TI  - Antisense oligonucleotide to AT1 receptor mRNA inhibits central angiotensin
      induced thirst and vasopressin.
AB  - Antisense oligodeoxynucleotides (AS-ODN) to AT1 receptor mRNA inhibit high blood
      pressure in Spontaneously Hypertensive Rats (SHR) when injected into the brain.
      The effect is presumably through inhibition of the actions of brain angiotensin
      II (Ang II). Central injection of Ang II elicits several physiological responses
      including release of vasopressin and motivation to drink. The angiotensin II type
      I (AT1) receptor is located in brain regions which have been implicated in
      mediating these effects. Therefore we hypothesized that AS-ODN to AT1 mRNA would
      inhibit the drinking and AVP response to central administration of Ang II in
      adult male SHR. AS-ODN were constructed to bases +63 to +77 (15-mer) of the AT1
      receptor RNA. 24 h after AS-ODN treatment (50 micrograms/4 microliters)
      (intracerebroventricularly, i.c.v.), the drinking response to Ang II (50 ng,
      i.c.v.) was significantly reduced in the SHR (P < 0.05). The drinking response to
      Ang II (i.c.v.) was also reduced in the Sprague-Dawley rats (P < 0.05). There was
      no reduction of water intake in the control animals treated with scrambled ODN
      (SC-ODN). Repeated injection of AS-ODN did not produce a greater reduction in
      drinking response. Arginine vasopressin (AVP) release to central Ang II was
      significantly decreased after AS-ODN treatment when compared to vehicle (P <
      0.05) and to SC-ODN injections (P < 0.05). Radioligand binding assays of the
      hypothalamic block after AS-ODN treatment showed a significant decrease of AT1
      receptor binding (P < 0.05). The results show that the antisense inhibition of
      brain AT1 receptor gene expression decreases the Ang II induced drinking and AVP
      release responses.

PMID- 7716288
TI  - [Magnetic resonance in the evaluation of Mullerian duct anomalies].
AB  - Mullerian duct alterations in development or fusion in the embryo cause
      congenital uterine anomalies which may be responsible for decreased fertility or
      problems in carrying out a normal pregnancy. In this study, the MR findings in
      uterine agenesis (1 case), unicornuate (2 cases), didelphys (3 cases), bicornuate
      (3 cases), arcuate (6 cases) and septate uterus (8 cases) are described, together
      with the optimal section planes for their demonstration. The examinations were
      performed with an 0.5-T superconductive magnet, the spin-echo technique and
      mostly T2-weighted sequences. The anomalies were grouped according to Buttram and
      Gibbons classification, which is the most used in clinics. In particular, the
      bicornuate uterus was distinguished from the septate uterus, the latter
      associated with the highest spontaneous abortion rates, on the basis of external
      fundal outline appearance. In such anomalies, the muscular or fibrotic nature of
      any intracavitary septum was assessed based on septal thickness more than on
      signal intensity at this level. MR diagnostic accuracy in 23 patients with
      Mullerian anomalies, compared with surgical, hysteroscopic, laparotomic and
      laparoscopic findings, was 100%. Nevertheless, if Mullerian duct anomalies
      responsible for gynecologic-obstetric problems are known or suspected, MRI should
      always be used, on the basis of a close gynecologist-radiologist collaboration,
      for classification agreement and the evaluation of any intracavitary septum
      morpho-biometric appearance and possibly nature, to discuss treatment options.

PMID- 7716287
TI  - [Ultrasound aspects in AIDS-related splenic diseases].
AB  - The authors reviewed retrospectively 139 splenopathies detected during 432 US
      examinations of the abdomen in AIDS patients to assess the role of US in
      correlation with anamnestic-clinical data and histologic findings in 45 cases.
      Splenomegaly was the main sign of abnormal splenic conditions, since it was
      present in all the examined patients. Twenty-one cases exhibited focal lesions.
      Non-Hodgkin's lymphomas were the only kind of neoplastic condition, which were
      detected in 15% of cases. In 57% of cases splenopathy was correlated with an
      infective agent, with a marked prevalence of Mycobacteria-i.e., tubercular in 26%
      and atypical in 22%. In the splenopathies with histologic confirmation which
      exhibited a focal US pattern (47%), US proved to be useful in assessing splenic
      involvement, however aspecific its signs, and in its monitoring, especially in
      the lesions with unexpected colliquative evolution, as in two cases of atypical
      mycobacteriosis.

PMID- 7716289
TI  - [Stress urinary incontinence in women: magnetic resonance assessment].
AB  - The preoperative radiologic study of female stress urinary incontinence is still
      incomplete and often not well tolerated. MRI is becoming a major diagnostic tool
      for pelvis assessment also thanks to its allowing dynamic studies. Therefore, MRI
      was used for the static and dynamic assessment of the pelvic floor, which is
      compromised in stress incontinence, in a series of 21 patients. Dynamic studies
      were reliable in all but two cases. Our MRI technique demonstrated anatomical and
      functional stress urinary incontinence alterations, such as the increased
      distance between urethra and pubic symphysis (16 patients), vaginal changes (7
      patients), levator ani muscle changes (9 patients) and urethropelvic ligaments
      changes (9 patients). The functional changes caused by pelvic floor collapse were
      observed in all the patients with reliable dynamic studies, i.e., the posterior
      urethrovesical angle was increased and the pelvic floor excessively lowered
      during pelvic strain. Our preliminary results suggest that MRI can play a major
      role in the preoperative assessment of stress urinary incontinence,
      notwithstanding the fact that the exam is performed with the patient supine and
      therefore with no gravity.

PMID- 7716290
TI  - [Ovarian varicocele: percutaneous treatment. A preliminary note].
AB  - Incontinence of ovarian veins and development of adnexal varicosities (pelvic
      varicocele) seems to cause pelvic pain syndrome in about 50% of the cases.
      Whereas the diagnosis of male varicocele is usually clinical, the same diagnosis
      in a woman needs instrumental methods; therefore the number of diagnosed cases is
      lower than the real incidence of the disease. In the last 18 months 2 patients
      with ovarian varicocele and chronic pelvic pain have been successfully treated by
      percutaneous sclerotization of the gonadal veins with resolution of the pelvic
      pain syndrome. We preferred this interventional procedure to the surgical one, as
      is usually the case with male varicocele, where percutaneous therapy is
      considered the treatment of choice on the basis of long-term results, since its
      first attempt in 1977. Considering the effectiveness of this simple and non
      surgical therapy for chronic pelvic pain, we stress the importance of correct and
      early diagnosis of pelvic varicocele.

PMID- 7716291
TI  - [Ultrasound and the bone: a difficult relationship].
AB  - The principles of US physics and technology hampering both the production of US
      images of the bone and the assessment of the soft tissue structures underlying it
      are discussed. In theory, two US parameters play a role in this field: the
      different transmission velocity of the US beam through soft tissues and bone, and
      the marked attenuation of the US beam when crossing the bone. The former
      parameter, due to higher density and lower compressibility of the bone with
      respect to soft tissues, causes both intense reflection (and thus beam weakening)
      and refraction (and thus lateral resolution and US image distortions) at the soft
      tissue/bone interfaces. Moreover, US transmission velocity in the bone differs
      significantly from the reference velocity of the US scanners on the market based
      on that of soft tissues. As a consequence, during the reconstruction of a bone US
      image, artifacts resulting in the axial compression of bone structures should, at
      least in theory, occur. The latter parameter, due to both conversion into heat
      (absorption) and local dispersion (scattering), is likely to be main factor
      causing the loss of US energy when the US beam passes through the bone. Although
      the amount of matter (bone mass or density) undoubtedly accounts for some
      attenuation, local bone architecture (bulk and shear moduli of bone and marrow,
      bone and marrow density, marrow viscosity and porosity, permeability and
      tortuosity of cancellous bone structure) seems nevertheless also responsible for
      some attenuation through both absorption and scattering. Other consequences of
      attenuation reflecting on US imaging of the bone are: marked lowering of central
      transducer frequency and US beam widening preventing the correct identification
      of the interfaces originating echoes by relating them to the structures on the
      transducer axis. In conclusion, based on the above parameters,
      echoencephalography and transcranial Doppler US can be expected to improve, in
      the near future, their bone-crossing capabilities, even though no true gray-scale
      bone sonogram will ever be feasible.

PMID- 7716292
TI  - [Ultra-low field magnetic resonance in the diagnosis of ovarian lesions].
AB  - To investigate the diagnostic capabilities of ultra low field MRI in the
      characterization of adnexal conditions, 46 women (aged 17 to 83 years) with US
      diagnosis of tubo-ovarian diseases were examined with MRI. An 0.064 T permanent
      magnet was used (toshiba Access), with T1- and T2-weighted spin-echo (SE)
      sequences, 3D T1-weighted gradient-echo (GE) sequences and, in 5 patients, a STIR
      sequence. Compared with surgical (37 patients), needle biopsy (3 patients) and
      clinical follow-up (6 patients) findings, MR diagnostic accuracy was 86.9%, which
      is comparable with literature data at higher field strength. The most common
      diagnostic error in our series was in the differential diagnosis between dermoid
      cyst and endometriosis which exhibited similar MR patterns. This limitation seems
      to be overcome by using STIR sequences with 60 ms T1 which, at this field
      strength, can suppress fat signal completely, whereas blood signal intensity
      remains high. The MR signal patterns of each group of conditions are also
      reported: in some cases, such patterns differ from those reported at higher field
      strength due to different T1 and T2 tissue relaxation times.

PMID- 7716293
TI  - [Magnetic resonance aspects of the bone marrow in aplastic anemia at the onset
      and in the follow-up after transplant].
AB  - Aplastic anemia is a rare hematologic disorder characterized by hypocellular
      fatty marrow. Aplastic anemia is diagnosed on the basis of laboratory tests and
      bone marrow biopsy findings. Biopsy is of fundamental importance for bone marrow
      assessment, though not representative of the rest of the marrow. Thanks to its
      exclusive capabilities in the direct visualization of bone marrow, MRI is a
      noninvasive and relatively rapid method for bone marrow study. The authors report
      their experience in 3 aplastic anemia patients examined also with MRI at
      presentation and after marrow transplantation. The dorsolumbar spine was studied
      with sagittal SE T1-weighted and STIR sequences, while pelvic bones were
      investigated only with SE T1-weighted sequences in all patients. Two of them were
      also examined with sagittal scans of the dorsolumbar spine using the chemical
      shift fat suppression technique. In all three patients, SE T1-weighted images at
      presentation showed fatty bone marrow infiltration, also confirmed on fat
      suppression images, and, after transplantation, progressive bone marrow
      repopulation, with the typical "band" pattern in vertebral marrow. Although MR
      specificity remains low in the demonstration of bone marrow disorders, the
      authors believe it to be a useful tool, after accurate clinical and laboratory
      exams, not only in the diagnosis but also and especially in the follow-up of
      these disorders.

PMID- 7716294
TI  - [Diagnostic image management and communication systems: experience at the
      University of Pisa].
AB  - Our work was aimed at implementing and validating a system for the acquisition,
      local management and remote transmission of diagnostic images. Integration of
      imaging equipment was performed in each of the two sites (5 km apart) in which
      the Department of Radiology of the University of Pisa is divided. Teleradiology
      was carried out using 64 Kbit/s lines as well as a 140 Mbit/s Metropolitan Area
      Network compliant with the Distributed Queue Dual Bus standard. Application
      domains included remote expert consultation and teleprocessing of diagnostic
      images. Remote expert consultation was performed in particular by using the 34
      Mbit/s interconnection with the Metropolitan Area Network of Florence. Remote
      processing of diagnostic images using the high speed link allowed the cooperative
      work with scientific institutions in a field often limited by the complexity of
      image transfer and by the lack of a timely feed-back concerning the clinical
      value of processed images. Advanced processing of diagnostic images was performed
      in the field of stereographic display of CT and MR data sets. Moreover,
      experience was gained in the visualization, on a single composite image, of the
      multiparametric data obtained by means of different MR sequences (T1, Spin
      Density, T2), thus allowing to summarize, by using false colors, different tissue
      contrast information.

PMID- 7716295
TI  - [Integrated imaging of the breast. Use of a hypermedia program and multimedia
      archives for teaching purposes].
AB  - This paper deals with the results obtained with a computerized senology system
      developed at the Institute of Radiology of "La Sapienza" University in Rome. The
      system combines a hypermedia program with a multimedia didactic archive
      integrated with the radiologic information system. These programs have been
      developed on Macintosh computers: the hypermedia one on a Macintosh IIfx with 160
      Mb hard disk and 8-Mb RAM and a Supercard software, the multimedia archive on
      Macintosh IIvx, IIvi and Quadra 650 units, connected with an Ethernet network to
      a server Quadra 950 (RAM: 20 Megabytes; optical disk: 1 Giga) and using the 4th
      Dimension as software. The basics of breast anatomy, radiologic semiology and
      breast diseases are illustrated with the hypermedia program: such a system has
      many advantages to teach the basics requiring just a process of learning by
      heart. The multimedia archive allows to classify a large number of difficult and
      uncommon clinical cases, according to the ACR code. Thus, it is useful also to
      teachers to study particular subjects, including anatomical variants and uncommon
      conditions. In conclusion, we believe these systems to be valuable tools in the
      formation and update of the physicians devoted to the study of breast diseases.

PMID- 7716296
TI  - [Treatment of Kaposi's sarcoma by transcutaneous radiotherapy and water bolus].

PMID- 7716297
TI  - [Determination of computer tomography dose index by means of ion chamber
      measurements].
AB  - The effective dose (ED) and the organ dose given with Computer Tomography (CT)
      scanners can be determined by means of a computing method suggested by the
      English National Radiological Protection Board (NRPB). This method uses the
      integral air-dose profile as input. Due to the non-rectangular shape of the CT
      profiles, a Computer Tomography Dose Index (CTDI) has been defined, as the
      integral dose profile divided by nominal slice thickness. The experimental
      determination of the CTDI can be carried out with thermoluminescent dosimeters.
      However, the measurement can be simplified by using a cylindrical ion chamber.
      This paper reports the calibration of a PMO5 ion chamber (5 cm3 in volume and 5
      cm in length) in terms of sensitivity value (4.45 pC mGy-1 mm-1). CTDI
      measurements by means of a PMO5 ion chamber were used to determine the effective
      doses and lung doses for the CT scanners used at the Institute of Radiology of
      the Catholic University in Rome. The dose levels thus obtained are in agreement
      with other national and international data. Moreover, the method allows the
      differences in the doses absorbed by the patients submitted to CT with different
      technical approaches to be calculated.

PMID- 7716298
TI  - [Pigmented villonodular synovitis of the shoulder. Description of a case
      diagnosed by magnetic resonance].

PMID- 7716299
TI  - [Color Doppler ultrasonography of the breast. Image results].

PMID- 7716300
TI  - [Congestive splenomegaly associated with massive splenic infarct and multicentric
      venous thrombosis. A case report].

PMID- 7716301
TI  - [Papillary and solid tumor of the pancreas. A case report].

PMID- 7716302
TI  - [Hematometra in urogenital malformations: a rare cause of postmenarchal acute
      abdomen].

PMID- 7716303
TI  - [Possibility of using self-expanding uncoated stents in benign esophageal
      stenosis. Experience in a case of post-irradiation stenosis].

PMID- 7716304
TI  - [Townes-Brocks syndrome (anus, hand and ear syndrome). A case report].

PMID- 7716305
TI  - [A prosthetic plug in repair of crural hernia using Lichtenstein's technique. A
      possible false-positive ultrasound of surgical sponge].

PMID- 7716306
TI  - [Impingement syndrome of the shoulder. Clinical data and radiologic findings].
AB  - Subcoracoid impingement syndrome pain is elicited by some positions of the upper
      limbs, i.e., adduction and inward rotation, whenever coracohumeral space reduces.
      Although acquired or congenital malformations of the humeral head and/or coracoid
      apophysis are the most common causes of painful syndromes, repeated flections and
      inward rotations of the upper limbs, typical of some sports, such as swimming and
      tennis, and of some sports, such as swimming and tennis, and of some kinds of
      work, are predisposing factors. The subcoracoid impingement syndrome exhibits on
      pathogenomonic signs at clinics and the specificity of diagnostic methods is low,
      which calls for reliable radiologic assessment of this condition. Fifteen
      patients with subcoracoid impingement syndrome underwent X-ray, US, CT and MR
      studies. Plain radiography detected no specific signs of this syndrome, but
      yielded useful information regarding other painful syndromes of the shoulder,
      such as anatomical variants of the acromion and degenerative changes. US yield
      was poor because of the acoustic window of the coracoid apophysis, but
      supraspinatus tendon changes were demonstrated in 2 cases. CT and MRI proved to
      be the most reliable and accurate diagnostic methods, the former thanks to its
      sensitivity to even slight bone changes and to its capabilities in measuring
      coracohumeral distance and acquiring dynamic scans and the latter because it
      detects tendon, bursa and rotator cuff changes. To conclude, in our opinion, when
      the subcoracoid impingement syndrome is clinically suspected, plain X-ray films
      should be performed first and followed by MR scans.

PMID- 7716307
TI  - [Study of torsion defects of the lower limbs using computerized tomography].
AB  - January, 1990, to July, 1993, the torsional defects of the lower limbs were
      studied at the Department of Radiology of the Istituto Ortopedico Rizzoli,
      Bologna. Ninety-three patients were examined, all of them affected with
      congenital or acquired (posttraumatic and/or iatrogenic) torsional defects. The
      torsional angles, i.e., the anteversion acetabulum angle, the anteversion femoral
      neck angle and the tibial torsion angle, were measured as follows: the patients
      were laid supine with their limbs either in intrarotation with the patella
      perpendicular to the table (62 patients) or in neutral rotation with the feet in
      the pace position (31 patients). The images were always analyzed at the console
      by two different radiologists in the following days. The electronic lines for
      measuring torsional angles were drawn by the two radiologists ex novo on the
      previously acquired CT images. No statistically significant differences were
      observed between the two groups of patients. The measures were independent of
      limbs position and the interobserver differences were bigger in children and in
      the measurement of femoral neck anteversion angle; however, these differences
      decreased by about 50% with better console use. CT, thanks to its feasibility,
      has replaced conventional (direct or indirect) radiology to study the torsional
      defects of the lower limbs. Moreover, CT is extremely useful not only for early
      disease diagnosis (location, rotation degree and associated joint deformities),
      but also for treatment planning, be it surgical or conservative.

PMID- 7716311
TI  - [Has the role of radiology changed in the fight against pulmonary tuberculosis?].
AB  - Tuberculosis is on the increase in Italy as in other industrial countries. The
      key to tuberculosis control is case finding and radiology plays a major role in
      both active and passive tuberculosis diagnosis. Have recent advances in
      radiologic techniques increased the value of conventional radiology? Has the role
      of chest radiography changed in tuberculosis screening? To answer these questions
      we examined a population referred to our hospital for both screening and
      diagnostic purposes over a 12-month period. In a population of 31,730
      inhabitants, 1,461 chest radiographs were performed, 226 (15.4%) for passive and
      the others for active case finding. As for active case finding, high-risk
      patients were screened (21 immigrants and 296 aging people), together with the
      general population believed to be at risk according to current national
      recommendations (918 chest films). While screening allowed the diagnosis of only
      one tuberculosis case in the high-risk group, 3 cases were found in the
      symptomatic group with the passive protocol. In our experience, new radiologic
      techniques have not made the diagnosis of tuberculosis easier. Unlike in cancers,
      CT was not particularly useful in identifying symptomatic tuberculosis cases. In
      our experience, screening yielded poor results: in fact, this attempt at
      preventing tuberculosis caused an unreasonable waste of time and money because
      when screening low-risk groups many films are needed to diagnose a single case.
      Thus, the reason for this failure was not a technical one. It proved to be a
      problem of selecting the population to be screened. Our results suggest that no
      major change has taken place in the role of conventional radiology in passive
      tuberculosis case finding and that radiology must be used differently in passive
      case finding, that is, for screening purposes in high-risk groups only.

PMID- 7716309
TI  - [Hematoma and fat necrosis of the breast: mammographic and echographic features].
AB  - The mammary gland is a common site for traumas which often lead to the formation
      of intraglandular hematomas. The abundance of fat tissue in this gland accounts
      for the relatively high frequency of fat necrosis and self-digestion of fat by
      lipases after traumas, i.e., fat necrosis, cystosteatonecrosis, lipophagic
      granuloma. Broadly speaking, hematomas are easily diagnosed by both mammography
      and US. However, scarring and the formation of lipophagic granulomas due to
      hemorrhage result in the diagnostic features which are difficult to distinguish
      from malignant breast nodules. In our study, we examined 40 patients with a
      clinically detected nodule and/or hematoma with skin retraction or thickening
      related to trauma. In 26 women, the trauma dated to 7-60 days before our
      observation, in 4 women to a year before and in 4 other women to more than two
      years before; 6 women had undergone breast surgery in the last two years.
      Mammography and US were performed at first observation; later, every six months,
      the patients were followed-up with US and a single targeted radiograph. The
      mammographic features at first observation were classified as follows: a single
      nodule (9 patients, 22.5%), a patchy nodule (7 patients, 17.5%), diffusely
      increased gland density (8 patients, 20%), radiolucent nodules (10 patients,
      25%), nodules with calcifications (6 patients, 15%), no findings (2 patients,
      5%). US demonstrated a fluid collection in 12 patients (30%), a solid nodule in 6
      patients (15%), a cystic nodule in 10 patients (25%), diffuse parenchymal
      abnormalities in 4 patients (10%), calcified nodules in 6 patients (15%) and no
      findings in 2 patients (5%). US-guided needle biopsy was performed in 10
      patients. Five patients underwent surgical biopsy: 4 had a lipophagic granuloma
      and the other one a chronic inflammation. Follow-up at two years allowed hematoma
      evolution to a scar or cystosteatonecrosis to be monitored. To conclude, the
      authors analyze the diagnostic problems related to the different mammographic and
      US patterns trying to suggest, on the basis of their own experience, the best
      imaging follow-up for breast trauma patients.

PMID- 7716308
TI  - [Retrospective analysis of color Doppler ultrasonography and flowmetry findings
      in solid nodular pathology of the breast].
AB  - The authors tried to identify useful flowmetric values and color-Doppler patterns
      for the differential diagnosis between benign and malignant solid breast lesions.
      To this purpose, 106 patients with breast nodules detected at mammography and/or
      high resolution US were examined. A US scanner with a linear 7.5 MHz transducer,
      a narrow sample volume, a PRF ranging (650-800 Hz) and a wall filter value of 50
      Hz were used. Three parameters were considered: the number vascular sites,
      systolic peak velocity and pulsatility index. All these parameters related to
      tumor volume. Several (> 2) vascular sites, high peak velocity and quite high
      pulsatility index were demonstrated in malignant tumors (46 lesions). Among
      benign tumors no vascular site was identified in 32 of 60 lesions and no more
      than 2 sites were identified in 26 of 60 lesions, except for 2 phylloides tumors.
      Sensitivity, specificity, positive and negative predictive values and overall
      accuracy rates were, as for the "vascular sites" parameter, 78%, 96%, 94%, 85%,
      88%, respectively; as regards the "peak systolic velocity" 81%, 86%, 89%, 75%,
      83% respectively; as regards the "pulsatility index" 100%, 85%, 100%, 85%, 94%
      respectively.

PMID- 7716312
TI  - [Signs of inflammatory activity in thoracic sarcoidosis. A high-resolution
      computerized tomography study].
AB  - Sarcoidosis is characterized by the presence of non-caseating granulomas.
      Lymphadenopathy and diffuse parenchymal abnormalities often involve the chest.
      This study was aimed at finding out signs that could be suggestive of disease
      activity and if the lesions are reversible after therapy. Sixty-three patients
      underwent chest radiography, high resolution CT, functional studies,
      bronchoalveolar lavage and 67Ga scintigraphy. Twenty-three patients were followed
      up. Lymphadenopathies, nodular opacities and acinar opacities resolved after
      steroid therapy; bronchiolectasies, bronchiectasies, septal thickening and
      parenchymal distorsion did not disappeared after therapy and are therefore
      considered as irreversible lesions. Ground glass opacities are an uncommon
      finding; they are due to fibrosis or to widespread interstitial granulomas rather
      than alveolitis. The prognostic meaning of ground glass opacities is uncertain.
      Therefore, disease activity findings are mainly lymphadenopathies, nodules and
      consolidations. Nevertheless these findings not necessarily imply a bad
      prognosis, as acute sarcoidosis seems to respond well to steroid therapy, even
      with complete remission. It remains debated if a CT study is worthwhile in all
      the new cases of sarcoidosis or only in the clinically more severe ones.

PMID- 7716313
TI  - [Magnetic resonance angiography in liver transplant patients. Follow-up of
      vascular anastomoses].
AB  - Twenty liver transplant patients were examined with MRA and color-Doppler US 18
      to 40 days after surgery to investigate the onset of vascular complications after
      surgical liver revascularization. Vascular anastomoses are the most frequent
      location for such complications as stenoses, occlusions, pseudoaneurysms and
      vessel ruptures. In liver transplant there are 4 vascular anastomoses, i.e.
      hepatic artery, portal vein and superior and inferior anastomoses of the inferior
      vena cava. MRA images were acquired with a superconductive unit operating at 1.5
      T, using fast low angle shot (FLASH) 2D sequences on the coronal plane; all
      images were postprocessed with the MIP algorithm. The presence of a paramagnetic
      artifact, the "double black spot sign", caused by the suture wire used to make
      the vascular anastomoses, allowed us to precisely detect the site and the flow
      pattern alterations at this level. MRA images were studied by two independent
      observers and vascular anastomosis depiction was rated as "good", "fair" and
      "poor". The demonstration of portal vein anastomoses was good in the whole series
      (20/20 patients). The superior anastomosis of the inferior vena cava was clearly
      depicted in 19 cases and fairly depicted in only 1 patient. The inferior
      anastomosis of the inferior vena cava was clearly depicted in 19 patients and
      fairly depicted in 1 case. Hepatic artery anastomoses were far more difficult to
      demonstrate than the others, considering their caliber and flow pattern, but its
      depiction was nevertheless good in 12 cases, fair in 6 and poor in only 2
      patients. In our series, only one portal vein stenosis was observed, which was
      clearly depicted on both MRA and US images. In conclusion, MRA is a useful and
      reliable noninvasive diagnostic tool to study vascular anastomoses in liver
      transplant patients.

PMID- 7716314
TI  - [Saint Michael Archangel, Patron Saint of radiologists. Summary of faith, history
      of customs and relations between radiation, bishops and pontiffs].

PMID- 7716316
TI  - [Diagnosis of gastroesophageal reflux in childhood. Comparison of ultrasonography
      and barium swallow].
AB  - Gastroesophageal reflux (GER) is a very common event in the pediatric patient. An
      accurate and atraumatic imaging technique must be used to differentiate normal
      from abnormal conditions. Sonography (US) appears to answer this purpose, as
      recently shown in the international literature. One hundred and seventy-eight
      patients with suspected GER were enrolled in this study; their age ranged 10 days
      to 15 years. They were examined with both US and barium swallow, in a double
      blind trial. The patients were divided into three groups, according to GER
      severity, i.e., absent or physiologic GER, moderate GER and severe GER. We
      considered not only the number of reflux episodes, as related to patients' age,
      but also reflux volume, esophagus clearing time and possibly coexisting hiatal
      hernia or esophagitis. US and barium swallow results were in agreement in 93% of
      the cases. In the other cases US demonstrated more severe GER than barium meal.
      No statistically significant differences were observed in the various age groups.
      Since US is a relatively cost-effective, noninvasive and physiologic method which
      is widely available and uses no ionizing radiations, it can be recommended as the
      screening test of choice in symptomatic children and in the follow-up.

PMID- 7716310
TI  - [Magnetic resonance myelography. Preliminary experience].
AB  - Three-dimensional (3D) MR Myelography is a new technique using constructive
      interference steady-state (CISS) sequences, which are characterized by a
      symmetric flow compensation enhancing CSF signal intensity compared with neural
      and extradural structures. 3D myelographic projections with different rotation
      angles are obtained from the 3D dataset with a mathematical algorithm called
      maximum intensity projection (MIP). Myelographic projections yield a global view
      of subarachnoid spaces and of root sleeves with no intrathecal contrast agent
      injection. This study was aimed at assessing the feasibility, the clinical value
      and the diagnostic accuracy of 3D MR Myelography in comparison with conventional
      myelography. From September 1992 to January 1994, thirty-five myelograms were
      performed. The study population consisted of 10 volunteers, 8 patients with
      traumatic brachial plexus lesions, 7 with herniated disks (4 lumbar and 3
      cervical disks), 4 with sacral radicular cysts, 2 with spinal vascular
      malformations, 3 with extramedullary intradural neoplasms (2 cervical neuromas
      and 1 cervical meningioma) and 1 with an intramedullary tumor (a conus medullaris
      ependymoma). All patients underwent SE MRI and conventional myelography (22
      lumbar injections, 3 cervical injections of nonionic iodinated contrast agent)
      followed by CT (CT myelography). This trial demonstrates the feasibility of 3D MR
      myelography in the study of the cervical and lumbar spine: its results are
      comparable to those obtained with conventional myelography also in some specific
      indications like traumatic brachial plexus injuries, where invasive conventional
      myelography is usually thought to be essential.

PMID- 7716315
TI  - [Pneumoperitoneum caused by thoracic injury].
AB  - Among the various causes of free abdominal gas, there should be included those
      following chest injuries. In these cases, pneumoperitoneum may develop as a
      consequence of different physio-pathologic mechanisms and can be associated with
      pneumothorax and/or pneumomediastinum and/or retropneumoperitoneum. Gas can reach
      the peritoneal cavity in both blunt and penetrating chest traumas, following
      normal or abnormal pathways, i.e., diaphragmatic interruptions in the former case
      and congenital defects or post-traumatic diaphragmatic injuries in the latter
      case. In this trial, the authors investigated the clinical and semiologic meaning
      of this finding, frequently disregarded in traumatologic literature, which was
      observed in 6 cases of chest injuries: 4 blunt and 2 penetrating traumas. In this
      condition, even though conventional radiology remains the method of choice, CT
      can be considered as an integrative technique of great panorama allowing small
      amounts of free abdominal gas and related thoracic and abdominal injuries to be
      demonstrated, especially in the patients in forced supine decubitus, in whom
      abdominal plain films can be difficult to perform.

PMID- 7716319
TI  - [Magnetic resonance in surgical planning in hepatocarcinomas].
AB  - The diagnostic accuracy of Magnetic Resonance Imaging (MRI) in the preoperative
      staging of unifocal hepatocellular carcinoma (HCC) was investigated and compared
      with that of ultrasonography (US) and Computed Tomography (CT). Eighteen patients
      with focal HCCs underwent MRI, CT and US scans before surgery. In all cases the
      histopathologic diagnosis was made with CT-guided fine-needle aspiration biopsy
      (FNAB). The diagnostic accuracy of each imaging modality was investigated with
      the assessment of three parameters thought to be of the utmost importance for
      surgical planning, i.e., lesion unifocality, the presence of a capsule and
      finally vascular involvement. MRI proved to be more sensitive than CT in
      demonstrating both lesion unifocality (100% vs. 94.4%) and the presence of a
      capsule (100% vs. 71.4%). In 2 of 18 patients some blood vessels were involved,
      which was clearly demonstrated only by MRI, CT missing it. Both MRI and CT had
      100% specificity in the detection of a perilesional capsule and of vascular
      involvement. To conclude, MRI exhibited higher diagnostic accuracy than US and
      CT, thus confirming its major role in the preoperative staging of unifocal HCCs.

PMID- 7716320
TI  - Prevalence of cytomegalovirus infection in different patient groups of an urban
      university in Brazil.
AB  - This study sought for evidence of previous CMV infection in patients of a general
      hospital serving the low income population of Rio de Janeiro. An enzyme
      immunoassay was used to detect anti-CMV antibodies in 713 typical hospital
      patients classified into eight different groups. Positive tests were found in 87%
      of pregnant women, 85% of newborns, 61% of pediatric patients, 77% of adolescent
      patients, 81% of adult patients, 87% of dialysed transplant candidates, 89% of
      kidney donors, and 92% of patients after transplantation. Depending of the
      subgroup studied these results carry different meanings and necessitate different
      clinical approaches. The risk of congenital disease is probably low in view of
      the reduced number of pregnant women still susceptible to primary infection. The
      number of primary infections will also be low in transplant recipients. However,
      those still susceptible will almost certainly acquire the infection from their
      donor. Prophylactic CMV matching in kidney transplantation is not a realistic
      approach due to the low probability of finding pairs of seronegative donors and
      recipients.

PMID- 7716322
TI  - [The developmental cycle of Rhodnius nasutus Stal, 1859 studied in the
      laboratory].
AB  - The biological cycle of Rhodnius nasutus was studied from november 1985 to
      September 1986 under laboratory conditions. The temperature ranged from 28.0 +/-
      2 degrees C to 22.0 +/- 2 degrees C and 59.2 to 70.4% of humidity. Chickens were
      used as a blood meal source. The complete biological cycle was achieved with an
      average of 209.4 days of the 16 remaining insects from initial colony of the 30
      Katomines. The average incubation period lasted 11.1 days and those for the
      following nymphal stages were: 17.6 days for the first; 16.1 days for the second;
      30.1 days for the third; 71.2 days for the fourth and 79.9 days for the fifth
      nymphal stage.

PMID- 7716317
TI  - [Laparoscopic ultrasonography in laparoscopic surgery and diagnosis].
AB  - The authors report their experience with 101 patients examined with laparoscopic
      ultrasound (LU) using a dedicated 7.5-MHz linear probe which can be introduced
      through the 10-mm surgical trocars. In the patients undergoing laparoscopic
      cholecystectomy (77 cases), LU adequately demonstrated gallbladder wall and
      contents in all cases and visualized the main bile duct in 93.5% of cases; stones
      of the CBD or cystic duct were demonstrated in two cases. The liver was studied
      in 18 patients undergoing diagnostic laparoscopy or laparoscopic colonic
      resection: secondary lesions were identified in two cases, while benign lesions
      (cysts or angiomas) were seen in 6 cases. In the patients operated on for colonic
      resection (8 cases), LU was successfully used to localize the enteric tract
      affected by the tumor and to mark safety margins for excision. The technical
      features of the exam are reported and the main imaging findings discussed. The
      authors conclude that LU is a safe method which is easy to perform and does not
      significantly increase the operating time; the indications of this laparoscopic
      application of ultrasound are not yet defined but the application area will
      certainly widen in the future, as operative and diagnostic laparoscopy are more
      and more frequently used by surgeons.

PMID- 7716321
TI  - [A comparative study of the incidence of sudden death from Chagas' disease in
      Uberaba in the years 1980 and 1990].
AB  - A comparison was made between the years 1980 and 1990 for the frequency and
      causes of sudden death occurring in the urban and rural areas of the city of
      Uberaba in individuals older than 15 years. It aims mainly to analyse the current
      frequency of sudden death in that region and to evaluate the impact, it any, of
      prophylaxis and therapy on sudden death due to Chagas' disease. For the 1226
      deaths cases studied from our 1980, 54 (4.4%) were sudden ones; out of these, 13
      (24.1%) were supposedly due to Chagas' disease. For the 1740 death cases studied
      form our 1990 series, 44 (2.5%) were sudden ones; out of these, only 3 (6.8%)
      were considered to be due to Chagas' disease. The results indicate a significant
      decrease in the frequency both for sudden death in general and for sudden death
      due to Chagas' disease when the year 1990 is compared with 1980. Probable
      explanations for the findings are discussed.

PMID- 7716318
TI  - [Use of safety catheter after removal of Kehr's tube in liver transplant
      patients].
AB  - The authors report on the use of a safety catheter when removing the T-tube in
      the patients with choledocho-choledochal biliary reconstruction after liver
      transplantation. After T-tube removal, bile may leak into the peritoneal cavity
      through the catheter insertion site in the biliary wall. Biliary peritonitis,
      bilomas, subhepatic collections may develop, which are difficult to treat in
      immunodepressed patients. The safety catheter is used to allow the external
      drainage of the biliary outflow, if present, and to prevent the complications due
      to bile collecting in the peritoneal cavity. Moreover, the catheter allows
      cholangiography and interventional procedures to be performed when necessary. A
      soft guidewire is inserted into the distal bile duct through the T-tube and
      pushed into the duodenum. After removing the T-tube, an 8.3-F all-purpose
      catheter (APD) is placed on the guidewire with the tip just outside the biliary
      wall. The APD is then connected to a drainage bag allowing the amount of bile
      eliminated daily to be checked. This maneuver was performed in 24 transplant
      recipients and the safety catheter correctly positioned in 22 of them (91.6%).
      The APD was removed 48 hours after insertion in 15 patients with no biliary
      leakage. In the remaining 7 patients the catheter was left in situ up to 8 days,
      since biliary leakage was observed (range: 50-400 ml/day). No early or late
      complications related to this technique were observed.

PMID- 7716323
TI  - [The isolation of Streptococcus morbillorum from vaginal exudates].
AB  - We have tested 195 vaginal secretions sent by Gynecology Service of this hospital
      between the years 1988-1990. We achieved positive culture for streptococci in 58
      (30%) of these cultures, 26 (44.8%) corresponding to Streptococcus morbillorum 9
      (15.5%), to Gardnerella vaginalis 5 (8.6%), to Enterococcus faecalis-durans and
      to Streptococcus agalactiae, 3 (5.1%) to Streptococcus mitis and milleri 2
      (3.4%), to Streptococcus bovis and cremoris, and 1 (1.7%) to Streptococcus
      salivarius, equinus and sanguis II respectively. We previously found that 52.8%
      of these patients were positive for vaginal candidiasis. The bacteriological
      identification done by the API 20 STREP System (bioMerieux GmbH, Nutingen,
      Germany) provides a typical pattern ("good identification") for the Streptococcus
      morbillorum.

PMID- 7716324
TI  - [A control program for an outbreak of the scorpion Tityus serrulatus, Lutz and
      Mello 1922 in the town of Aparecida, Sao Paulo state (Scorpiones, Buthidae)].
AB  - A scorpion control program was proposed for the town of Aparecida (SP), an
      endemic region of Tityus serrulatus. Clusters of scorpions in urban and rural
      areas, environmental degradation of the town's outskirts and new scorpion
      procreation and dispersal habitats were studied. In addition, infrastructure
      problems such as the disposal and collection of residential and municipal refuse,
      sanitation (sewage and storm sewer), condition of vacant lots and constructions
      in the urban area were evaluated. After an epidemiological study, educational
      measures such as the distribution of pamphlets, cleaning group work, visits to
      residences and cooperation from High School teachers and students were also
      suggested. Chemical control was indicated in high-risk sites, especially those of
      near-school buildings. Furthermore, the use of natural predators was also
      mentioned within the present sanitation regulations for urban areas. The authors
      assert that these procedures must be integrated and continued uninterruptedly for
      several years. They also suggest a collaborative work with those responsible for
      the dengue eradication program, as well as the institution of the "scorpion study
      week", which would greatly contribute to the education of the population, to
      preventive programs and to scorpion control.

PMID- 7716325
TI  - [The use of a silicone T tube for the treatment of a case of American
      mucocutaneous leishmaniasis with tracheomalacia].
AB  - The authors report a case of mucosal leishmaniasis, in which tracheomalacia and
      respiratory insufficiency occurred. The nature of the illness, the patient's
      general condition and the great extension of the affected tracheal segment made
      segmental resection and anastomosis inviable. The silicone T tube, which proved
      itself useful, was the choice, thus motivating this report of the procedure.

PMID- 7716326
TI  - [Anisocoria in the chronic phase of Chagas' disease].
AB  - To compare the frequency of anisocoria in patients with chronic Chagas' disease a
      prospective double-blind study was done in 131 patients with positive serology
      for Chagas' disease and 138 negative, at Mambai (GO-Brazil), which is an endemic
      area for Chagas' disease. To detect anisocoria, pupillometry was done with a
      millimetric ruler. Anisocoria was seen in 10(7.6%) patients with Chagas' disease
      and in 3(2.1%) normal subjects. The chi-square test showed statistical
      significance at level of 5%. Chagas' disease must be included among the causes of
      anisocoria.

PMID- 7716328
TI  - [Nipple involvement in diffuse cutaneous leishmaniasis (DCL) produced by
      Leishmania (L) amazonensis].

PMID- 7716327
TI  - [Spotted fever in the town of Pedreira, Sao Paulo state, Brazil. The relationship
      between the occurrence of cases and human parasitism by ixodid ticks].

PMID- 7716329
TI  - [Epidemiological data on malaria for all of Brazil in 1993].

PMID- 7716330
TI  - Scabies.

PMID- 7716332
TI  - [References for evaluation scales in quality assurance in rehabilitation--1. I.
      Scales for determining adverse sequelae of illnesses--an introduction].

PMID- 7716331
TI  - Evaluation of a direct immunofluorescent antibody (DIFMA) test using Leishmania
      genus-specific monoclonal antibody in the routine diagnosis of cutaneous
      leishmaniasis.
AB  - A direct immunofluorescent antibody (DIFMA) test using a Leishmania genus
      specific monoclonal antibody was evaluated in the routine diagnosis of cutaneous
      leishmaniasis (CL) in Ecuador. This test was compared with the standard
      diagnostic techniques of scrapings, culture and histology. Diagnostic samples
      were taken from a total of 90 active dermal ulcers from patients from areas of
      Ecuador known to be endemic for cutaneous leishmaniasis. DIFMA was positive in
      all lesions. It was shown to be significantly superior to standard diagnostic
      methods either alone or in combination. The sensitivity of DIFMA did not diminish
      with chronicity of lesions. This test proved to be extremely useful in the
      routine diagnosis of CL because it is highly sensitive, is easy to use and
      produces rapid results.

PMID- 7716333
TI  - [References for evaluation scales in quality assurance in rehabilitation--1. II.
      Measuring functional independence in rehabilitation with the Functional
      Independence Index].
AB  - Presented is an instrument assessing functional independence in rehabilitation.
      This instrument, the Functional Independence Measure (FIM), was developed in the
      USA and translated into German. Considerable experience and research has
      accumulated concerning its application, formal properties and function in
      interdisciplinary rehabilitation. Application and evaluation of the FIM is
      demonstrated in a case study. The FIM is shown to be a reliable and highly
      informative instrument measuring disability according to ICIDH criteria in
      clinical practice. It reflects reliably the amount of help and assistance
      required by the individual patient.

PMID- 7716334
TI  - [Maastricht European social policy with special reference to questions concerning
      rehabilitation and disability topics].
AB  - A protocol annexed to the Maastricht Treaty of 7 February 1992, the agreement on
      social policy is instrumental in upgrading European social policy and in making
      it an integral part of the policy of the European Union. It is on the one hand
      oriented toward appropriate provisions to protect workers in the various EU
      member countries against disadvantage arising from developments in the economic
      sector, but on the other also seeks to counter the high level of unemployment
      currently at hand by fostering concrete action. European social policy, hence, is
      emphasizing employment policy initiatives including action aimed at occupational
      and social integration of disabled people, such as the HELIOS II action programme
      or the "Employment HORIZON" Community initiative. The Commission's notions of
      European social policy development in the forthcoming 1995-1999 period have been
      presented in the White Paper "European social policy, a way forward for the
      Union". The proposals contained in this White Paper are to be embodied in 1995 in
      a work programme of the European Commission.

PMID- 7716335
TI  - [Which patients in psychosomatic rehabilitation can be reached by
      psychotherapy?].
AB  - This report presents a cross-sectional study of the patients in a psychosomatic
      clinic (n = 112). Possible predictors concerning psychotherapeutic cooperation of
      patients are presented and discussed. Negative predictors found were: The
      presence of two or more strictly somatic rehabilitation treatments in the past; a
      therapist rating of "not capable of being motivated for psychotherapy"; a pension
      application, or a degree of disability of 50 ("severely disabled person" status).
      A positive predictor for psychotherapy is a patient's previous experience with
      psychosomatic therapies. Some consequences are discussed concerning indication as
      well as client information, preparation of clients prior to clinical treatment,
      and cooperation with other institutions providing psychosocial services.

PMID- 7716336
TI  - [Progress in disability pensions for psychosomatic patients].
AB  - Only part of the invalidity pensioning courses seen can be traced to medically
      substantiated illness and disablement. Another part of these courses, with an
      extraordinarily high share in particular from the psychosomatic field, consists
      of a gradual psychosocial down-grading which, though possibly triggered by
      illness and disablement, essentially is enhanced, or countered, by specifies of
      individual personality, family, labour market, or medical doctors' behaviour. The
      matter dealt with only seems to be a dry one. The fates of those affected are
      oppressive, regardless of whether pensioning ensues or not. Frequently, the
      entire family is involved by the improvement taking place. At the same time,
      enormous spending accumulates due to the coverage provided by the statutory
      health and pension insurance schemes. It is therefore considered appropriate that
      an invalidity pensioning study be conducted specifically directed at pensioning
      behaviours, at clarifying the weight of the various factors involved and at
      investigating the effectiveness of rehabilitative instruments in the various
      phases. The findings should form the basis also for improved preventive
      approaches, such as energetic measures to combat meaningless certification of
      illness or "parking-off" of patients in long-term unemployment, while
      rehabilitative service provision is totally neglected.

PMID- 7716337
TI  - [Evaluation and quality assurance in neurorehabilitation].
AB  - Quality assurance is among the dictates of the hour and should, through integral
      feedback, lead to on-going methodical improvement. It must not be mistaken for
      merely comprising control measures decreed from higher up. The following is
      brought forward: 1. Humaneness must be the overruling principle. 2. The
      methodological specifics of the various disciplines and the needed range of
      methods on the one hand have to be accepted with all their complexities, yet on
      the other be tied into an appropriate quality assurance system with certain norms
      and standards. 3. We were able to develop the "Barolin-Reha-Scale", which has
      proved its efficiency in neuro-rehabilitation and has several advantages over the
      previously available scales. 4. In addition, on-going patient self-assessment
      must routinely be carried out, although we certainly are well aware of the many
      "subjectivity factors" involved. 5. The above can only come to bear if meaningful
      controls are permanently established in addition to the necessary motivational
      and organisational measures.

PMID- 7716338
TI  - [Changes in subjective health in sports participating and sedentary patients
      after 4-week treatment in a rehabilitation clinic].
AB  - Presented are selected findings of a study of 62 patients who had participated in
      a four-week inpatient treatment programme in a health-resort rehabilitation
      clinic due to complaints of the locomotor organs. The patients' physical and
      general complaints showed statistically significant reductions in the course of
      this programme participation. Similar effects were stated as well for the
      majority of the scales pertaining to subjective health. A correlation between
      physical activity and subjective wellbeing, or physical complaints, respectively,
      has not been stated for all of the subjective health-related scales and
      complaints items. The improvements achieved can be considered proof of the
      effectiveness of the clinic's overall therapeutic concept as well as of the
      social relief afforded by the rehabilitation clinic setting.

PMID- 7716339
TI  - [Possibilities of sports medicine consultation for multi-handicapped patients].
AB  - In the framework of a project of the Northrhine-Westfalian disabled sports
      association, 42 multihandicapped residents of the von Bodelschwinghschen
      Anstalten Bethel participated in a sports medical study, with usefulness and need
      for sports medical examination and consultation clearly confirmed. Spirometric
      testing procedures were shown to require review. Close cooperation among staff,
      coaches as well as sports medical specialists is indispensable for ensuring
      meaningful implementation of the results as well as enhanced health through
      physical activity and sports.

PMID- 7716340
TI  - [Resolution: "Significant increase in language development disorders in children
      requires rapid management". German Society for Rehabilitation of Handicapped e.
      V].

PMID- 7716341
TI  - [Empirical results of adjustment to disability by adolescents with spina bifida
      and traumatic paraplegia].
AB  - Between June 1991 and June 1992, a total of 39 rehabilitees aged 16 to 25 years
      were examined, i.e., 21 patients suffering from spina bifida and 18 patients
      suffering from traumatic paraplegia. Diagnostic instruments used were the
      Freiburg questionnaire on coping with illness (FKV 102), Goldberg et al's
      questionnaire for the evaluation of subjective wellbeing regarding health, and a
      self-constructed questionnaire for evaluating satisfaction with rehabilitation.
      Medical interviews on the present state of health and the present situation were
      held with each patient. The level of paralysis was taken as an indicator of the
      motor handicap present. The patients examined showed distinctly less confidence
      in doctors than adults do. From a subjective point of view, however, the
      confidence in doctors was good: among the coping strategies chosen, the
      compliance strategies ranked first and second, respectively, in the two groups.
      The coping strategy of "cognitive avoidance and dissimilation" is distinctly less
      common among spina bifida patients than among patients with traumatic paraplegia.
      They are less inclined to hope for a miracle, and take their handicap much more
      seriously than adolescents suffering from traumatic paraplegia. The higher the
      level of paraplegia, the more use is made of the coping strategy of "emotional
      control and social withdrawal". Regressive tendencies and depressive modes of
      coping were equally present in both groups. When investigating satisfaction with
      rehabilitation and with the own person, both groups showed very high satisfaction
      with the physical independence achieved and the possibilities of acting
      independently.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716342
TI  - Lovastatin ameliorates depressed intraglomerular proteolytic activities in
      experimental nephrotic syndrome.
AB  - Lipid abnormalities have been implicated in the pathogenesis of
      glomerulosclerosis in experimental models of kidney disease. In previous studies
      it has been shown that Adriamycin-induced nephropathy is associated with reduced
      activities of glomerular proteinases. This observation led to the hypothesis that
      reduced proteolytic activities may be responsible for mesangial protein
      accumulation, which ultimately leads to global sclerosis of the glomerular tuft.
      The aim of the present study was to investigate whether lovastatin treatment,
      which prevents progressive glomerulosclerosis in experimental nephrotic syndrome,
      would also have an effect on glomerular proteinase activities. Adriamycin
      administration resulted in a persistent nephrotic syndrome with gross proteinuria
      (377 +/- 26 mg/24 h), hypoalbuminemia (2.1 +/- 0.12 vs. 2.8 +/- 0.02 g/dl),
      hypercholesterolemia (575 +/- 74 vs. 68 +/- 1.5 mg/dl) and elevated triglyceride
      levels (1,155 +/- 78 vs. 57 +/- 8 mg/dl). Glomerular azocaseinolytic activities
      both at pH 5.4 (-21%) and 7.4 (-37%) were significantly reduced. In contrast to
      human subjects, nephrotic rats that were treated with lovastatin displayed
      reduced triglyceride levels (767 +/- 134 mg/dl); their serum cholesterol,
      however, remained unchanged. In terms of glomerular proteolytic enzyme
      activities, the decline in azocaseinolysis at both pH values was, at least
      partly, prevented by lovastatin. On the basis of these data, it appears that the
      beneficial effect of lovastatin on the evolution of glomerulosclerosis in the
      nephrotic rat is associated with the conservation of glomerular proteolytic
      activities.

PMID- 7716343
TI  - Effect of nitric oxide inhibition on capsaicin-elicited vasodilation in the rat
      oral circulation.
AB  - The effects of local application of capsaicin on the vascular conductance of the
      oral structures (upper gingiva, lower gingiva, tongue, right and left
      submandibular glands) were studied with and without pretreatment with NG-nitro-L
      arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide formation in
      rats. Alterations in tissue blood flow were measured by laser-Doppler-flowmetry;
      systemic blood pressure was monitored continuously during the experiments. Local
      application of increasing concentrations of capsaicin (1.0; 3.33; 10.0; 33.3 mM;
      in a volume of 5 microliters) resulted in a dose-dependent increase in the
      vascular conductance of all tissues investigated. There was a significant
      correlation between the values obtained for vascular conductance in the right and
      the left submandibular glands. Bolus intravenous injection of L-NAME (10 mg kg-1)
      elevated the mean systemic blood pressure significantly, by about 20%, with a
      rapid onset. This increase persisted until the end of the experiment. The
      augmentation of vascular conductance elicited by 10.0 mM capsaicin, locally
      administered, was significantly diminished in animals pretreated with L-NAME in
      all tissues tested. The results indicate that nitric oxide formation plays a
      significant role in the enhancement of vascular conductance produced in rat oral
      structures by local capsaicin administration.

PMID- 7716345
TI  - Naloxone interferes with granulocytopoiesis in long-term cultures of mouse bone
      marrow; buffering by the stromal layer.
AB  - Long-term cultures of mouse bone marrow cells were treated with naloxone,
      starting at the time of culture initiation or in the 2nd or 4th week of culture.
      Cell proliferation was suppressed and the ratio of immature and mature
      granulocytes to macrophages diminished by naloxone treatment. The effect depended
      on the timing of naloxone addition to the cultures and on its concentration, with
      a bell-shaped dose-response curve. High and low concentrations of naloxone (10(
      4), 10(-6), 10(-14) M) interfered with hematopoiesis more strongly than the
      intermediate concentrations (10(-8) to 10(-12) M). Early cultures lacking the
      stromal layer were more sensitive to naloxone than the cultures with established
      stroma. The bell-shaped dose-response curve has been attributed to an interplay
      of specific (opioid-receptor-mediated) and nonspecific mechanisms. Opioidergic
      mechanisms apparently participate in the regulation of hematopoiesis.

PMID- 7716344
TI  - A new experimental model of specific liver hypoxia using membrane oxygenator.
AB  - The present study introduces a new experimental canine model of hepatic arterial
      deoxygenation using a membrane oxygenator to investigate the influence of hepatic
      arterial hypoxia on hepatic hemodynamics and energy metabolism. Eighteen mongrel
      dogs weighing 10 kg each were randomly divided into three groups: group A served
      as a control (118.0 +/- 9.0 mmHg of hepatic arterial O2 content), group B as a
      moderately deoxygenated group (40 mmHg of hepatic arterial O2 content), and group
      C as a severely deoxygenated group (25 mmHg of hepatic arterial O2 content).
      Deoxygenation was achieved by perfusion of a gas mixture of O2 and N2 through the
      membrane oxygenator, which was interposed between the femoral artery and the
      proper hepatic artery, for 60 min. In group C, hypoxia decreased the mean
      systemic arterial blood pressure and hepatic arterial blood flow. Arterial blood
      ketone body ratio (AKBR = acetoacetate/3-hydroxybutyrate), which reflects the
      hepatic mitochondrial redox state, rapidly decreased prior to the significant
      increase of glutamate oxaloacetate transminase, glutamate pyruvate transminase,
      and lactate dehydrogenase after the initiation of hypoxia. Hepatic arterial
      deoxygenation to 25 mmHg for 60 min induced injury to hepatic hemodynamics,
      resulting in the deterioration of systemic hemodynamics even after the
      termination of liver hypoxia. This in vivo temporal hepatic arterial hypoxic
      model without alteration of inflow volume might be useful for investigating the
      mechanism of hypoxic injury and the critical point of liver hypoxia on hepatic
      and/or systemic hemodynamics and liver viability.

PMID- 7716346
TI  - Morphometric study of centrilobular vessels in the rat liver after continuous
      hypothermic perfusion with Euro-Collins and University of Wisconsin solution.
AB  - Damage to the hepatic microcirculation plays an important part in the
      preservation-related loss of graft viability. In a study on the isolated,
      hypothermically preserved rat liver perfused continuously with Euro-Collins and
      University of Wisconsin solution (gluconate substituted for lactobionate) at
      different flow rates we determined changes in diameter of central veins and
      pericentral sinusoids and related them to weight changes. While post-perfusion
      liver weight increased with Euro-Collins and decreased with University of
      Wisconsin solution, weight changes did not vary significantly with different flow
      rates. Changes in sinusoidal diameter depended on the type of solution as well as
      on the flow rate. Cell swelling under Euro-Collins perfusion leads to compression
      of pericentral sinusoids, which varies in degree with different flow rates.
      Perfusion with University of Wisconsin solution under near-normal flow, due to
      slight shrinking of parenchymal cells, keeps the sinusoidal lumina wide open. We
      conclude that there is a causal relationship between perfusion-dependent cell
      swelling and reduction in sectional area of the hepatic microvasculature.
      Continuous hypothermic perfusion with University of Wisconsin solution at
      physiologic flow rates excellently preserves the size and trabecular architecture
      of hepatocytes and thereby the sinusoidal lumina within the hepatic lobules.

PMID- 7716347
TI  - Diagnostic yield of transthoracic needle aspiration biopsy following negative
      fiberoptic bronchoscopy in 103 patients with peripheral circumscribed pulmonary
      lesions.
AB  - The diagnostic potential of secondary transthoracic needle biopsy (TNB) following
      negative fiberoptic bronchoscopy (FOB) in patients with peripheral circumscribed
      pulmonary lesions was evaluated in a retrospective study. The records from 224
      patients who had TNB over a 5-year period were reviewed. Of these, 103 patients
      met the criteria for inclusion in this series. The overall diagnostic yield of
      TNB in malignancy was 73.8% (54 of 73 patients). TNB allowed cytologic
      classification of the tumor type in 72.2% (39 of the 54 patients). Five of the 54
      patients (9.3%) presented with small-cell anaplastic bronchogenic carcinoma,
      diagnosed at TNB, and were referred to chemotherapy. Of the 49 patients with a
      negative TNB, 27 went on to diagnostic surgical procedures; 19 had malignancy, 3
      benign tumor, 2 infection, and 3 sequelae after pulmonary infarction. The
      remaining 22 undiagnosed patients were followed up over a long period of time, 5
      showed progression of the pulmonary lesion suggesting malignancy. TNB appeared
      unsuitable for the diagnosis of benign lesions. Unspecific inflammation was not
      considered evidence of benignity, and therefore no definitive benign diagnosis
      was made by TNB in this series. There were no serious complications to TNB. In
      18.1% of the procedures a pneumothorax developed, indicating a chest tube in 8.6%
      of the procedures. TNB is a suitable diagnostic procedure with a high diagnostic
      yield in patients with peripheral localized malignant pulmonary lesions.

PMID- 7716348
TI  - Positive end expiratory pressure reduces bronchial blood flow after aspiration
      injury.
AB  - We hypothesized that since added airway pressure compresses bronchial vessels,
      the airway hyperemia found following airway injury would be reduced by positive
      end-expiratory pressure (PEEP). Accordingly, we measured the effect of 15 cm H2O
      PEEP on bronchial and pulmonary blood flows by the radioactive microsphere
      reference flow technique in closed chested goats (n = 7) before and after
      aspiration injury to the left lung with 0.1 N HCl. Thirty minutes after
      aspiration, the pulmonary blood flow to the injured left lung was reduced by one
      third, whereas the total bronchial blood flow to the left lung (normalized to
      mean systemic pressure of 100 torr) doubled (11.3 +/- 2.2 to 20.6 +/- 1.0 ml/min
      100 torr; p < 0.01). Increasing PEEP from 5 to 15 cm H2O decreased total
      bronchial blood flow by about half both before (11.3 +/- 2.2 falling to 5.7 +/-
      1.4 ml/min/100 torr) and after injury (20.6 +/- 1.0 falling to 10.3 +/- 2.7
      ml/min/100 torr). The airway portion (down to 2-3 mm airways) of the total
      bronchial blood flow of the injured lung increased more than three-fold (1.4 +/-
      0.5 rising to 5.5 +/- 1.3 ml/min/100 torr; p < 0.01). This increased flow after
      aspiration was less affected by PEEP of 15 cm H2O (5.5 +/- 1.3 to 2.8 +/- 0.7
      ml/min/100 torr, p = 0.09) than before injury (1.4 +/- 0.5 falling to 0.5 +/- 0.1
      ml/min/100 torr; p < 0.05). The increase of the parenchymal portion of the
      bronchial blood flow after injury, although apparent (9.9 +/- 1.8 increasing to
      15.1 +/- 1.2 ml/min/100 torr), was not significant (p = 0.08).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7716349
TI  - Effect of bamiphylline on tracheobronchial mucus clearance in subjects with
      smokers' simple chronic bronchitis.
AB  - A double-blind study versus placebo was performed to assess the effect of
      bamiphylline, a new xanthylic derivative, on tracheobronchial mucus clearance
      (TBMC) in smokers with simple chronic bronchitis and impaired mucus clearance as
      compared to normal controls. Twenty patients were enrolled and divided into two
      randomized groups. The first group was treated with bamiphylline (600 mg b.d.)
      for 15 days, while the second group received placebo with the same oral dosage
      regimen. Complete clinical-functional examinations were made before and after the
      test period to establish the effects of treatment. At the end of the study, only
      the group treated with bamiphylline showed a net increase in mucus clearance
      (mean radioaerosol elimination 28 +/- 7% before treatment and 38 +/- 11% after
      treatment; p < 0.01) and an improvement in the clinical score and pulmonary
      function parameters, in particular the residual volume (RV = 3.41 +/- 0.75 liters
      before treatment and 2.7 +/- 0.6 after treatment; p < 0.01) and the forced
      expiratory volume at 1 s (FEV1 = 2.37 +/- 0.7 liters before treatment and 2.88 +/
      0.5 after treatment; p < 0.05). No side effects or adverse reactions that could
      be attributed to the study drug were observed.

PMID- 7716351
TI  - Nonstructural protein 2 (NS2) of respiratory syncytial virus (RSV) detected by an
      antipeptide serum.
AB  - The human respiratory syncytial virus (RSV) is often associated with airway
      obstruction and is suspected to induce bronchial hyperreactivity. Interactions of
      viral proteins with cellular components may be responsible for epithelial damage
      leading to bronchial hyperreactivity. In this study, we describe the localization
      of the 14.7-kD nonstructural protein 2 (NS2) in RSV-infected cells. The detection
      of NS2 was performed using antipeptide antibodies elicited against amino acids
      109-123 of the predicted sequence of the NS2 protein. By using recombinant NS2,
      we could clearly demonstrate the specificity of the antipeptide antibodies. With
      this defined tool, NS2 could be first detected in infected HEp-2 cells at 10 h
      p.i. subsequently to the detection of N protein. In double-staining experiments,
      colocalization of NS2, P protein and N protein was demonstrated. The antipeptide
      antibodies recognized the NS2 protein in the sediment of RSV-infected HEp-2 cells
      lysed with RIPA buffer at 48 h p.i. The results agree with the reported
      interaction of RSV with cytoskeletal intermediate filaments. These interactions
      may implicate essential cellular functions suspected to induce bronchial
      hyperreactivity.

PMID- 7716352
TI  - Regulatory effects of aerosolized budesonide and adrenalectomy on the lung
      content of endothelin-1 in the rat.
AB  - This study was designed to investigate the effect of inflammation and
      glucocorticosteroids (GCS) on the content of endothelin-1-like immunoreactivity
      (ET-LI) in the rat lung. Following intratracheal instillation of Sephadex beads,
      which induces a long-lasting inflammation in the lung, there was an increase in
      the lung content of ET-LI measured by RIA. This increase was abolished by locally
      administered aerosolized budesonide at doses that had only minor systemic effects
      (measured as a reduction in body weight). In a second series of experiments, rats
      were subjected to surgical adrenalectomy in order to reduce the levels of
      endogenous GCS. This procedure elevated the ET-LI levels in the lungs. In
      contrast, neither adrenalectomy nor high doses of budesonide administered
      systemically affected the concentration of ET-LI in the kidney. It is concluded
      that the lung ET levels are elevated in inflammatory conditions and that this
      increase is highly sensitive to locally administered GCS. Endogenous GCS may,
      directly or indirectly, play a role in the regulation of lung ET content but
      there seems to be no general GCS effect on basal tissue levels of ET.

PMID- 7716353
TI  - Ventilatory pattern at rest and response to hypercapnic stimulation in patients
      with obstructive sleep apnea syndrome.
AB  - We studied the ventilatory pattern and mouth occlusion pressure (P0.1) at rest
      and the response to awake hypercapnic stimulation in 27 patients with obstructive
      sleep apnea syndrome (OSAS). The respiratory pattern was characterized by both
      increased P0.1 and VT/Ti (p < 0.05), with a higher VE (p < 0.01) due to a slight
      increase in VT. Ventilatory response to hypercapnic stimulation showed no
      significant differences with respect to the control group. Our findings reveal
      that OSAS patients show an increased minute output secondary to a mild degree of
      hyperstimulation on the baseline central ventilatory control and that there is a
      subgroup of patients with a decreased ventilatory response to CO2.

PMID- 7716350
TI  - Intrapleural Corynebacterium parvum for recurrent malignant pleural effusions.
AB  - Twenty-two consecutive patients with malignant pleural effusions (MPE) were
      treated with intrapleural Corynebacterium parvum (CBP) associated with parenteral
      methylprednisolone (MP) to determine its effectiveness and the frequency and
      nature of adverse reactions. After thoracentesis, 7 mg of CBP (Coparvax Wellcome)
      in 20 ml of saline were injected into the pleural cavity. On the day of
      treatment, the patients were given 1 mg/kg i.m. of MP 30 min before
      thoracentesis. The effectiveness of pleurodesis was assessed as follows: (1)
      complete response (CR; total resolution of pleural effusion after 3 injections of
      CBP at the most); (2) partial response (PR; formation of asymptomatic loculated
      effusion). In 5 patients leukocytes, lymphocytes and monocytes were determined in
      pleural fluid (PF) and in blood (B) collected before and 7 days after CBP
      treatment. Two patients were unevaluable. Of 20 evaluable patients, 18 (90%) had
      a CR and 2 patients (10%) had a PR. Eleven of 22 patients (50%) had a fever.
      Three patients had prolonged and/or high fever. Seven of 22 patients (32%) had
      mild chest pain. None of the patients presented other side effects. Twelve of 21
      patients (57.1%) had a PF pH > or = 7.30; 2 of these died a few days after the
      treatment, and 10 had favorable responses. The other 9 patients had a PF pH <
      7.30: all had favorable responses. The leukocytes, the lymphocyte subsets, the
      monocytes, the NK lymphocytes, and their PF/B ratios did not differ significantly
      before and after CBP treatment. Our study confirms that intrapleural CBP is an
      effective and simple method to control MPE.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716354
TI  - Long-term course of bronchiectasis and bronchiolitis obliterans as late
      complication of smoke inhalation.
AB  - We describe the long-term course of a patient with bronchiectasis and
      bronchiolitis obliterans, both of which developed as late complications of a
      smoke inhalation injury. Sequential chest X-rays obtained during the observation
      period showed gradual progression of bronchiectasis from the saccular to the
      cystic type. Symptoms, spirometry and blood gas analysis, however, remained
      stable for 15 years. We believe that symptoms and physiological derangement were
      due mainly to bronchiolitis obliterans, and that once the pathophysiological
      condition had been established following the initial injury, it could be
      maintained by conservative medical management.

PMID- 7716355
TI  - Tracheopathia osteoplastica simulating asthmatic symptoms. Diagnosis by
      bronchoscopy and computerized tomography.
AB  - Tracheopathia osteoplastica (TO) is a relatively rare benign disease of the
      trachea and major bronchi, characterized by cartilaginous and bony submucosal
      nodules covered by intact mucosa, which may cause narrowing and rigidity of the
      upper airways. The diagnosis of TO is rarely considered because of a lack of
      awareness of this entity, rather than the reported rare occurrence. We intend to
      report herein a case initially misinterpreted as bronchial asthma but later
      disclosed through computerized tomography (CT) and bronchoscopic biopsies as TO.

PMID- 7716356
TI  - Multiple pleural tuberculomas associated with a cold abscess of the hip.
AB  - We report an unusual case of multiple pleural tuberculomas associated with a cold
      abscess of the hip. A 26-year-old man was admitted because of diffuse nodular
      thickening of the right pleura and an abscess of the left hip. Biopsies of the
      pleura and abscess of the left hip revealed tuberculosis. Antituberculous
      chemotherapy for 12 months improved both the pleural tuberculomas and the cold
      abscess of the left hip.

PMID- 7716358
TI  - Chronic pneumomediastinum and subcutaneous emphysema: association with
      dermatomyositis.
AB  - We describe a 41-year-old patient with adult-onset dermatomyositis who developed
      persistent pneumomediastinum and severe subcutaneous emphysema due to end-stage
      interstitial lung disease. The diagnosis of dermatomyositis was based on proximal
      muscle weakness, electromyographic findings of inflammatory myopathy, and
      positive findings on muscle biopsy. Low levels of creatine kinase elevation were
      found at the time of diagnosis (a form of dermatomyositis which has been
      associated with a poor prognosis). The patient had no signs of cutaneous
      vasculitis. Despite treatment with prednisone and azathioprine, she died of
      intercurrent gram-negative sepsis 15 months after the diagnosis of
      dermatomyositis.

PMID- 7716359
TI  - [The management of hemorrhagic portal hypertension. A new therapeutic
      alternative].

PMID- 7716357
TI  - Tracheal carcinoma and mixed pneumoconiosis. A causal relationship?
AB  - We report on a 58-year-old man who had worked as a plumber and fitter for over 41
      years and had been exposed to asbestos, man-made mineral fibers and welding
      fumes. Eighteen months before death, squamous cell carcinoma of the trachea
      occurred. Energy-dispersive X-ray analysis revealed intrapulmonal dust deposits
      in accordance with his exposure. A relationship between the tracheal carcinoma
      and the dust exposure causing a mixed pneumonoconiosis seems to be probable.

PMID- 7716360
TI  - [Biliary fistula following laparoscopic cholecystectomy].

PMID- 7716361
TI  - [Appendicitis in children under 3].
AB  - There are many differences between acute appendicitis in the older child and the
      infants. An understanding of the under three years of age child's response to
      intra-abdominal infection in contrast to that of the older child and an
      appreciation for the supportive treatment of the child are vitally important in
      further lowering the morbidity of young children with acute appendicitis. The
      purpose of the present study was to investigate the factors contributing to the
      high perforation rate seen in this age group. A retrospective analysis was done
      in 88 patients under the age of three who underwent appendectomy. These patients
      ranged from 4 and 35 months in age. There were 51 (77.4%) male patients. The main
      complaints were fever, pain and vomiting. Duration of symptoms was more than 24
      hours in 80%. Abdominal radiographs showed signs of small bowel obstruction.
      Peritonitis was found in the majority of the cases (90%). overall morbidity was
      31.8% and mortality 1.1%. These data suggest that duration of symptoms is
      directly proportional to complications rate.

PMID- 7716362
TI  - [The transjugular intrahepatic portosystemic stent-shunt (TIPS) in the management
      of portal hypertension. A preliminary report].
AB  - Transjugular intrahepatic portosystemic shunt-stent (TIPS) was performed in 5
      patients with cirrhosis and portal hypertension. Bleeding varices occurred in 4
      patients and refractory ascites in one. We used 2 Wallstents and 3 Strecker
      stents. Shunt patency, recurrent variceal hemorrhage and ascites were evaluated.
      The shunts were created from a transjugular approach between the hepatic and
      portal vein, with diameters of 10 mm. Portal pressure was adequately decreased in
      all cases. The hospital stay, following TIPS was 3 days. Complete variceal
      decompression was identified endoscopically in 3 patients, and partial in one.
      Four shunts were patent by ultrasound and color Doppler at 1 to 6 months of
      follow up. One patient presented encephalopathy and one died at third day after
      TIPS. Initial results suggest that TIPS is an effective method of portal
      decompression for treatment of variceal hemorrhage and refractory ascites. The
      main complication was encephalopathy and only one patient died.

PMID- 7716363
TI  - [The local complications of appendicitis].
AB  - In order to find out the predisposing factors of local complications after
      appendectomy in two general hospitals, 268 charts of patients with acute
      appendicitis confirmed by surgery were reviewed. There were 142 males and 126
      females. All wounds were closed and prophylactic antibiotics were not used. Sixty
      patients (22 per cent) developed local complications; 49 (81.7 per cent) surgical
      wound infection and 11 (18.3 per cent) with intra-abdominal abscess. In the wound
      infection group 25 per cent had complicated acute appendicitis and only one per
      cent non-complicated acute appendicitis. The correlation between the preoperative
      period and wound sepsis showed, the longer period the higher incidence of wound
      infection, 1.7 per cent with less than 24 hr. 11 per cent with less than 72 hr.
      and 78.9 per cent with more than 96 hr.

PMID- 7716364
TI  - [Carcinoid of the proximal ileum].

PMID- 7716365
TI  - [Biliary fistulae following laparoscopic cholecystectomy].
AB  - Three cases with biliary fistulae through cystic duct after laparoscopic
      cholecystectomy are reported. The patients were discharged during the first post
      op day without any clinical problem. Until the first postoperative week, pain and
      fever were present. In every cases transendoscopic cholangiography were
      performed. The cannulation of the papilla was very difficult. We did not found
      any biliary structure or biliary duct lithiasis. The cases were treated by
      endoscopic techniques and/or minimal invasive procedures. An increased pressure
      of the biliary system may contribute to biliary fistulae. This can be secondary
      to Oddi's sphincter disfunction, and/or the use of metallic clip in adverse
      conditions. The opportune diagnosis and treatment prevent major complications.
      The initial endoscopic management is adequate to diagnose and solve this
      complication. The minimal invasive surgery is a good alternative to solve those
      cases that need additional treatment.

PMID- 7716366
TI  - [Epithelial hepatoblastomas in the adult].
AB  - Hepatoblastoma is the most frequent primary malignant liver neoplasm in
      childhood; in adults it is extremely rare and only 27 cases have been published.
      The prognosis of this neoplasm is poor because it is usually discovered late.
      Surgery, chemotherapy and liver transplantation have been tried with poor
      results. We present two adult patients who were diagnosed with an epithelial
      hepatoblastoma. The pathogenesis, histologic features and current management is
      reviewed.

PMID- 7716367
TI  - [Squamous cell carcinoma of the liver].
AB  - A case of primary squamous cell carcinoma of the liver in a 38-year-old male
      patient is informed. We could only find 13 cases reported in the literature, all
      of them in male patients; in the Mexican literature this histologic type of
      hepatic neoplasia has not been reported. The prognosis of these lesions are
      extremely poor, and no case has survived over six months.

PMID- 7716368
TI  - [Is the intestinal transplant a reality?].
AB  - Small bowel transplantation trials before cyclosporine was unavailable because of
      rejection, graft-versus-host disease and technical problems. With the discovery
      of cyclosporine, and another immunosuppressors like prednisone, antithymocyte
      globulin, azathioprine, OKT3 and the recent rapamycin, mycophenolate mofetil,
      deoxyspergualin, FK506, mizoribine and brequinar sodium, the prognosis for small
      bowel transplanted patients is better than before.

PMID- 7716369
TI  - [The behavior and perinatal impact of viral hepatitis in pregnancy].
AB  - The association between viral hepatitis and pregnancy is not common, nevertheless
      it has been described that hepatitis is the most frequent cause of jaundice in
      pregnant women. In this article the current knowledge on the perinatal
      repercussions of the different types of viral hepatitis are reviewed. Hepatitis A
      is rare during pregnancy and is not associated with perinatal risk. Hepatitis B
      virus (HBV) can be transmitted transplacentally, 20 per cent of the children
      infected by this route will develop liver cirrhosis or carcinoma in the adult
      age, so the infants of HBsAg carrier mothers must be immunized at born. The
      perinatal transmission of hepatitis C virus has been proved but the repercussion
      in the fetus or newborn is unknown. Hepatitis D virus can only be transmitted
      from mother to child together with HBV. Hepatitis E has been associated with a
      mortality of 10 to 40 per cent in pregnant women.

PMID- 7716370
TI  - [3rd division of the Surgery Clinic of the Hospital das Clinicas of F.M.U.S.P].

PMID- 7716371
TI  - Practical physiologic evaluation of the colon, rectum and anus.

PMID- 7716372
TI  - [Chagasic megacolon. Treatment by abdominal recto-sigmoidectomy with mechanical
      colo-rectal termino-lateral anastomosis. Preliminary results].
AB  - Abdominal rectosigmoidectomy with end to side colorectal mechanical anastomosis
      is proposed as a new technique for surgical treatment of Chagasic megacolon. The
      rectum is sectioned and closed at the level of the peritoneal reflexion. The end
      of the descending colon is anastomosed to the posterior surface of the rectum, as
      distal as possible, using the intraluminal stapler (Ethicon CDH33). The final
      result of the operation is similar to Duhamel-Haddad technique with the advantage
      of being a one stage operation. Forty-three patients with chagasic megacolon were
      operated on during the period 1989-1994. Twenty-seven were female and 16 were
      male with ages ranging from 23 to 76 and a mean of 46.1 years. Results obtained
      were satisfactory; there were no deaths; only three postoperative complications
      occurred (6.9%). Only one of these (dehiscence of the rectal cupula) was specific
      for the proposed technique. The two others were intestinal obstruction, due to
      volvulus of the small intestine in one case and to adhesions in the other. All
      complications were managed by surgery. All patients are being followed regularly
      and up to the present time they report daily bowel movements, passing well-formed
      stools. There are no complaints of fecal incontinence sexual function or
      disturbed formation of fecaloma in the rectal stump. The colorectal anastomosis
      was ample in all patients. Since this is a one stage operation with a low rate of
      complications, the short hospital stay largely compensates the cost of the
      mechanical suturing device. Regarding recurrences, a long follow-up period of at
      least 10 years is necessary to evaluate the real effectiveness of this technique.

PMID- 7716373
TI  - [Cystic neoplasm of the pancreas: analysis of 24 cases].
AB  - Cystic neoplasms are an uncommon group among pancreatic tumors. These lesions are
      seen more frequently in recent surgical practice, probably because of advances in
      diagnostic and surgical techniques. We report 24 patients with cystic tumors of
      the pancreas, including twelve patients with serous cystadenoma, ten with
      mucinous cystadenoma and two patients with mucinous cystadenocarcinoma. Twenty
      two patients were women and two were man. The median age of patients was 53.5
      years (range, 21 to 80 years). Mild abdominal pain was the main symptom; in 71%
      of patients and weight loss in 29% of patients. The lesions were incidental
      findings 8% of patients. The mean size of the cysts was 7.8 cm (range, 2.3 to
      15cm). Eleven cystic neoplasms were located in the head, three in the neck, five
      in the body, two in the tail of pancreas and three in the body and tail. All
      patients underwent surgical exploration. There was no perioperative mortality.
      Total tumor resection provides the best chance of cure and may remove the risk of
      malignant transformation of the cystadenomas, particularly of the mucinous type.

PMID- 7716374
TI  - [Mesenteric cyst].
AB  - Mesenteric cysts are rare abdominal tumors. Their incidence varies in different
      papers from one in 27,000 to one in 250,000 hospital admissions. Five patients
      with mesenteric cysts were treated at Hospital das Clinicas da Faculdade de
      Medicina da Universidade de Sao Paulo between November 1982 and October 1992. The
      most common location was in the small bowel (60%). All of them were treated by
      surgery. One case was found incidentally. Treatment of choice is enucleation. It
      was realized in two cases (40%). The others had segmental bowel resection.

PMID- 7716377
TI  - [Evaluation of medical teaching of clinical medicine in 6th year internship
      Medical School of USP].
AB  - The authors analyzed the performance of student's during their stay at the
      University Hospital of Sao Paulo. The study was based on: theoretical evaluation
      (tests), number of hours dispensed on standard textbook study, and participation
      in seminars and/or classes. The opinion of the students about the quality of the
      study of the internal medicine was also analyzed. The average number of hours
      designated to study the textbook's was 5.8 +/- hours/week. There was an increase
      in the presence at seminars from 10% to 72%.

PMID- 7716376
TI  - [Total regression of advanced gastric lymphoma after drug therapy].
AB  - Primary gastric lymphoma is a relatively rare entity that may have several
      different methods of treatment, including surgery, chemotherapy and radiotherapy.
      We describe a case of advanced primary gastric lymphoma treated with
      chemotherapy. A 51-year-old male patient underwent total gastrectomy after two
      cycles of chemotherapy. The histologic examination of the gross specimen revealed
      total regression of the lymphoma. Literature review of this condition and a
      discussion about the diagnosis and treatment are presented.

PMID- 7716378
TI  - [More accusations against the nursing profession].

PMID- 7716375
TI  - [Multicentric myxoid, metachronous and synchronous and multifocal liposarcoma:
      report of a case].
AB  - A case of a male patient, 66 years old, who exhibited in a period of six years
      many multicentric and multifocal synchronic and metachronic myxoid liposarcomas
      is reported. The authors made a revision of cytogenetics and DNA alterations
      recently identified in this type of tumor. The chromosomic alterations are
      represented by the translocation t(12;16) (q13;p11) and trisomy of the chromosome
      8. The genic analysis revealed the presence of altered restriction fragments due
      to highly specific and reproducible methylation differences. In conclusion the
      authors suggest that the presence of the multiple tumors of this type in the same
      patient could be due to a common etiologic factor, not yet known, as being the
      initiator of this systemic illness of the fat tissue.

PMID- 7716379
TI  - [Internal communication and perception of hospital services].

PMID- 7716380
TI  - [Improvement in the quality of assistance. A propos of a case].

PMID- 7716381
TI  - [Attitudes towards AIDS. A questionnaire for health professionals].

PMID- 7716382
TI  - [Television and public health. Effect of public campaigns for the prevention of
      traffic accidents].

PMID- 7716383
TI  - [The fifth national congress of the Spanish Society of Oncologic Nurses].

PMID- 7716384
TI  - [Treatment by enteral nutrition].

PMID- 7716385
TI  - [The femoral vein in an open presentation in order to show its 3 compartments].

PMID- 7716386
TI  - [Control of hospital infections in Spain. The nurse's role].

PMID- 7716387
TI  - [A computer program for the personal management of diets].

PMID- 7716389
TI  - [Crohn disease and parenteral nutrition].

PMID- 7716388
TI  - [System of self-measurement of glucose in capillary blood].

PMID- 7716390
TI  - Malaria parasites and chloroquine concentrations in Tanzanian schoolchildren.
AB  - Subtherapeutic doses of chloroquine (CQ) are considered to promote development of
      Plasmodium falciparum resistance but little is actually known about the drug
      levels in the population in endemic areas. We have therefore measured blood
      concentrations of CQ in Tanzanian schoolchildren and related these to parasite
      microscopy. A total of 163 children (median age 11 years) in a suburb outside Dar
      es Salaam were followed during four weeks. Thick and thin blood films were
      obtained once weekly. Parasites were counted in 200 visual fields. CQ and
      desethyl-chloroquine (DECQ) were determined with HPLC in 100 microliters of
      capillary blood. During the study P. falciparum trophozoites were detected in a
      mean of 78% of the children, P. falciparum gametocytes in 7.7% and P. malariae
      parasites in a mean of 13%. The cumulative prevalence of P. falciparum
      trophozoites and P. malariae parasites was 96% and 28% respectively. On day 0 and
      day 28, CQ was found in 78% and 80% of the children and DECQ in 21% and 31% of
      them. A total of 19% of all children had a verified CQ intake during the study
      and 35% had probably taken CQ. With a few exceptions (9% had CQ concentrations >
      100 nmol/l) drug levels were not sufficient to affect parasites with a reduced CQ
      susceptibility but could possibly promote development of resistance by
      eradicating the most susceptibility part of the parasite population.

PMID- 7716391
TI  - Liver profile changes and complications in jaundiced patients with falciparum
      malaria.
AB  - To demonstrate the liver profile abnormalities in jaundiced falciparum malaria
      patients and to determine whether jaundice was associated with other
      complications in falciparum malaria, 390 patients with acute falciparum malaria
      were studied. 124 patients were jaundiced and the others were non-jaundiced.
      Hyperbilirubinemia (total serum bilirubin 3 to 64 mg/dl) was found in jaundiced
      patients predominantly as unconjugated bilirubin. Asparatate amino-transferase
      and alanine minotransferase were significantly higher in jaundiced patients (p <
      0.01). There was a slight decrease of serum albumin in jaundiced malaria. The
      complications in jaundiced patients included cerebral malaria (n = 10), acute
      renal failure (n = 12), pulmonary edema (n = 3), shock (n = 3), and other severe
      malarial complications (n = 43). Jaundice was associated with cerebral malaria (p
      < 0.05), acute renal failure (p < 0.01), and hyperparasitemia (p < 0.01). After
      successful treatment, liver profile returned to normal within a few weeks. We
      found that jaundiced malaria patients had transient liver profile impairment
      which indicated predominantly hemolysis rather than liver damage; complications
      were more frequent in jaundiced patients.

PMID- 7716392
TI  - Chemical and thermal inhibition of protein secretion have stage specific effects
      on the intraerythrocytic development of Plasmodium falciparum in vitro.
AB  - The intraerythrocytic stages of the human malaria parasite Plasmodium falciparum
      induce a variety of physiological changes of the host erythrocyte. Many proteins
      are secreted from the parasite and are subsequently found at specific locations
      within the host cell. To elucidate the importance of protein secretion for
      parasite survival, infected red blood cells (IRBC) were subjected to the fungal
      metabolite brefeldin A (BFA) and to incubation at 15 degrees C, treatments that
      inhibit protein secretion and parasite development. Evidence is provided that
      retardation of parasite development in the presence of BFA correlates with an
      inhibition of protein secretion. Incubation at 15 degrees C and BFA reversibly
      arrest parasite development at the ring stage. Arrested ring stages loose 50% of
      their competence to develop to trophozoites after 1.5 days of treatment with BFA
      and after approximately 4 days at 15 degrees C. BFA affects development of
      trophozoites at concentrations similar to those required to arrest rings. In
      contrast to rings, the viability of trophozoites cultured at 15 degrees C or in
      the presence of BFA is completely abolished within 24 h.

PMID- 7716393
TI  - Development and evaluation of an enzyme linked immunotransfer blot technique for
      serodiagnosis of Chagas' disease.
AB  - An enzyme linked immunoelectrotransfer blot technique (EITB) was developed and
      evaluated for the serodiagnosis of Chagas' disease. EITB strips were prepared
      using Trypansoma cruzi (Y strain) epimastigotes lysate. Evaluation was performed
      with 235 serum samples collected from individuals living in an endemic area for
      Chagas' disease. Among those samples, 160 were serological positive in three
      conventional tests for T. cruzi and 75 were negative. The specificity was
      determined using 37 serum samples from patients with other infectious diseases.
      The EITB test showed sensitivity of 99.3% and specificity of 100% when a positive
      reaction was defined as the presence of 3 bands from a group of 7 (14, 19, 27,
      30, 34, 37 and 75), a negative reaction was defined as the absence of 6 of the 7
      bands, and an indeterminate reaction as the presence of two of the 7 bands.

PMID- 7716394
TI  - Mixed populations of Trypanosoma brucei in wild Glossina palpalis palpalis.
AB  - In many previous characterization studies of Trypanozoon, isolates have been
      subpassaged numerous times in laboratory rodents until a quantity of trypanosomes
      sufficient for analysis has been obtained. In addition to the numerous
      biochemical effects of such a process on the parasite, it appears probable that
      adaptation to an unnatural host may also serve to filter out less virulent
      populations from mixed infections, leading to an underestimate of the true level
      of genetic diversity. By the early cloning of trypanosomes from susceptible
      captive flies infected from the primary isolate--the midgut of a wild tsetse--the
      present study provides evidence of the range of genetically different Trypanosoma
      brucei populations which may coexist within the midgut of individual tsetse flies
      in nature. The three primary isolates from tsetse yielded one, five and nine
      genetically distinct populations. Cloned populations were confirmed as T. brucei
      using the polymerase chain reaction, and were characterized by karyotype analysis
      and multilocus isoenzyme electrophoresis. These data allowed a limited assessment
      of the level of genetic variability in natural populations of T. brucei.

PMID- 7716396
TI  - Preparation and sequence analysis of Taenia crassiceps metacestode recombinant
      antigens with potential for specific immunodiagnosis of human cerebral
      cysticercosis.
AB  - A Taenia crassiceps metacestode cDNA expression library in lambda gt 11 was
      screened with rabbit antisera to metacestodal T. solium and T. saginata crude
      extract. Primary clones (121) were identified, and after rescreening and
      lysogenization in Escherichia coli Y 1089, were tested in Western blot for
      reactivity with the same antisera. In addition, analyses were performed with
      rabbit antisera directed towards T. crassiceps and Echinococcus granulosus
      metacestode crude extract, sera from humans with neurocysticercosis (Mexico) and
      other important helminth diseases, mice and calves with experimental T.
      crassiceps and T. saginata infections and normal sera. Of those tested, 22 clones
      expressing beta-galactosidase fusion proteins (approximately 118-132 kDa) were
      reactive with IgG antibodies of cysticercotic patients and T. crassiceps infected
      mice. Of these clones, 11 were also sero-positive with calf-IgG antibodies
      against T. saginata larvae. None of the 22 clones reacted with IgG antibodies due
      to human cystic and alveolar echinococcosis, intestinal/hepatic or urinary
      schistosomiasis, African onchocerciasis or with sera from uninfected controls
      (man, rabbit, calf and mouse). Of these 22 clones, 15 have been subcloned into
      the plasmid vectors pGEX-2T (modified) and pT7T3 alpha 19. Expressed glutathione
      S-transferase fusion proteins were again tested for sensitivity and specificity
      by Western blot, and concentrated by affinity chromatography. The nucleotide
      sequence of the cDNA inserts of 9 clones has been determined in pT7T3 alpha 19
      and revealed identity in 4 and 5 clones, respectively.

PMID- 7716397
TI  - Human infection with Gongylonema pulchrum: a case report.
AB  - A 43 year old woman developed a painful tumor at the left buccal mucosa.
      Following local anti-inflammatory treatment a 35 mm long, living female adult
      worm of Gongylonema pulchrum was extracted from the affected side. No further
      treatment was needed and recovery was complete 5 days after extraction. Infection
      had occurred possibly 6 weeks before in Hungary with ingestion of contaminated
      water from an open draw well. Although commonly occurring as parasitic infection
      of domestic cattle and other vertebrates, gongylonemiasis is very rare in humans.
      Only 48 cases have been described in the literature since 1864. Life cycle and
      pathology of G. pulchrum are discussed.

PMID- 7716395
TI  - Urinary and intestinal schistosomiasis in the Tono Irrigation Scheme,
      Kassena/Nankana District, upper east region, Ghana.
AB  - Human- and snail-related aspects of transmission of urinary and intestinal
      schistosomiasis were studied in the Tono Irrigation Scheme in northern Ghana. The
      scheme became operational in 1977. In some schools, prevalences and intensities
      of both Schistosoma mansoni and S. haematobium infection were alarmingly high,
      pointing to human schistosomiasis being at least focally a health problem of
      major public health concern. Positive correlations between intensity of
      schistosome infection, as measured by egg output, with frequency of visible
      haematuria and history of haematuria point to opportunities for community-based
      assessment of morbidity and identification of high risk population subgroups.
      Bulinus globosus is the most important snail host for S. haematobium while
      Biomphalaria pfeifferi serves as host for S. mansoni. While transmission of S.
      mansoni is taking place only in the main canal, transmission of S. haematobium
      takes place in all parts of the irrigation system (lateral canal, night storage
      dam, main reservoir). Transmission of both S. mansoni and S. haematobium is
      rather focal and a seasonal pattern of transmission is indicated with peak
      transmission taking place during the beginning of the dry season. The high
      endemicity and the transmission patterns described in this study call for an
      integrated approach to schistosomiasis morbidity control in the area.

PMID- 7716398
TI  - Onchocerca volvulus: in vitro cytotoxic effects of human neutrophils and serum on
      third-stage larvae.
AB  - The cytotoxic effects of neutrophils co-cultured with infective third-stage
      larvae (L3) and autologous serum from three groups of individuals: infected
      (INF), non-patent endemic normals (EN) and non-endemic controls (NEC), were
      compared using a MTT (3-(4,5 dimethylthiazol-2yl)-2,5 diphenyl tetrazolium
      bromide) reduction assay as a biochemical parameter of larval viability. The MTT
      assay permitted the detection of L3 which had suffered varying levels of
      necrosis. The observations from this study indicate that infected individuals and
      endemic normals are capable of mounting a specific immune response against the
      infective L3. This is based on our findings of i) significantly greater numbers
      of L3 showed necrosis in neutrophil cultures of the INF and EN compared to those
      from the NEC, ii) a superior ability of cultures from these individuals to
      inhibit the molting of L3 to fourth-stage larvae, iii) IgG antibodies reactive
      with the surface of L3, detected by immunofluorescence in the serum of the INF
      and the EN and iv) recognition of specific antigens in extracts of L3 detected by
      Western blot analysis. The specific immune response directed against L3 is
      probably a significant immunological defense mechanism used to limit infection in
      endemic areas.

PMID- 7716399
TI  - Ivermectin-induced cell-dependent lethal effects on litomosoides carinii
      microfilariae in vitro.
AB  - Ivermectin affected the motility of Litomosoides carinii microfilariae in vitro
      in a dose dependent manner but did not completely immobilize the larvae and had
      no lethal effects when tested up to a concentration of 1000 ng/ml. However,
      killing of microfilariae was induced by ivermectin in vitro in the presence of
      spleen cells of Mastomys coucha or rats within 14 h. Optimum effects occurred at
      drug levels of 10-100 ng ivermectin/ml. Addition of infection serum led to
      increased cytotoxicity when compared with normal serum. Pretreatment in vitro of
      L. carinii microfilariae with ivermectin in cell-free medium and subsequent
      exposure to spleen cells caused also cytotoxic effects which appeared to be
      accelerated in comparison with simultaneous exposure of microfilariae to
      ivermectin and cells. Pretreated microfilariae, injected intravenously into naive
      M. coucha were rapidly eliminated from the blood of the recipients. These results
      suggest that the microfilariae become altered by the drug and thus susceptible to
      cell-mediated cytotoxic effects. Cytotoxicity did not depend on the attachment of
      cells to L. carinii microfilariae and was also induced when targets and effector
      cells were separated by membranes impermeable for cells. Thus ivermectin-induced
      cellular cytotoxicity to L. carinii microfilariae is at least partly mediated by
      soluble factors released by effective cells.

PMID- 7716400
TI  - Knowledge and attitudes toward onchocerciasis in the Thyolo highlands of Malawi.
AB  - In preparation for mass distribution of ivermectin to control onchocerciasis in
      the Thyolo highlands of Malawi a survey was conducted to determine knowledge and
      attitudes toward onchocerciasis which could assist in developing educational
      messages. Since onchocerciasis is not known by a specific name in the Thyolo
      highlands, information was sought about individual perceptions of common symptoms
      of infection. Itching, skin thickening, nodules, or depigmentation (leopard skin)
      were reported by 95% of those interviews. Effective treatment was often thought
      by the community to be available when actually it was not. Traditional healers
      were not thought to be an important source for treatment of lesions associated
      with onchocerciasis. None of those interviewed associated Simulium damnosum s.l.
      with any symptoms other those related to the actual bite. Based on the
      information gathered, various options for ivermectin educational messages are
      discussed.

PMID- 7716401
TI  - Parasitological and clinical studies on Wuchereria bancrofti infection in Chuuk
      (formerly Truk) State, Federated States of Micronesia.
AB  - A total of 2193 people in 14 villages on 9 islands was examined for microfilaria
      (mf). The average mf rate of those examined was 2.6%. High mf rates of 7-10% were
      obtained in 3 villages on 3 islands. Analysed by sex and age, the highest mf
      rates were observed among males of age > or = 20 years (6-10%). A clinical study
      conducted on 466 adult males of age > or = 15 years showed that the average
      hydrocele rate was 3.4% and that of elephantiasis 0.4%. For the ages > or = 50
      years the hydrocele rate was nearly 10%, indicating that filariasis is an
      important public health problem. Filariasis in Chuuk seems to be decreasing, but
      some endemic villages found in the study imply the existence of many unknown and
      thus unattended foci of filariasis in Pacific islands.

PMID- 7716402
TI  - Cytochemical analysis of the sheath of microfilariae of Wuchereria bancrofti and
      Brugia malayi.
AB  - Thin sections of Epon and Lowicryl embedded microfilariae of Wuchereria bancrofti
      and Brugia malayi were analyzed by transmission electron microscopy aiming at
      topochemical characterization of the sheath. Three layers could be distinguished.
      Some of the layers were labeled when incubated in the presence of antibodies,
      lectins and enzymes which recognize extracellular matrix components usually
      associated with the basal laminae lining epithelial cells.

PMID- 7716403
TI  - Stage specific differences in steady state levels of mRNA encoding the major
      surface glycoprotein of Brugia pahangi.
AB  - The glycoprotein, gp30, is the major soluble cuticular antigen of the adult
      lymphatic fiarial worm Brugia pahangi (Maizels et al., 1983, Devaney, 1988).
      Cookson et al., 1992 suggested that gp30 may function as an antioxidant enzyme
      protecting B. pahangi from the vertebrate host defence mechanism. In this
      communication we report that the gp30 transcript is present in each of the life
      cycle stages, including mosquito derived L3's, and that there is a 50 fold
      increase in the transcription of gp30 in young adults (28 days post infection)
      compared to mature adults. These findings suggest that gp30 performs a general
      function relevant throughout the B. pahangi life cycle and in particular to young
      adults.

PMID- 7716404
TI  - Complement sensitivity of Entamoeba histolytica and various nonpathogenic amoeba
      species.
AB  - Culture forms of the potentially pathogenic Entamoeba histolytica were compared
      to those of the nonpathogenic species of E. dispar, E. hartmanni, E. coli,
      Endolimax nana, and E. moshkovskii regarding the sensitivity to lysis by human
      complement activated through the alternative pathway. E. dispar was found unique
      in its complement resistance; all other nonpathogenic isolates resembled E.
      histolytica in that they were complement sensitive. Thus, a state of complement
      sensitivity is not a particular property of potentially pathogenic amoebae.

PMID- 7716406
TI  - [National Health Survey 1993].

PMID- 7716405
TI  - [In memory of Enrique Najera Morrondo].

PMID- 7716407
TI  - [Estimation of AIDS morbidity and mortality in Spain].
AB  - BACKGROUND: To obtain corrected estimates of the cumulative incidence and
      mortality, as well as prevalence of AIDS in Spain on June 1992. METHODS: The
      number of cases in the National Register of AIDS by December 1992 was adjusted
      for reporting delays to estimate the cumulative incidence by June 1992. The
      prevalence and mortality in this date were obtained using this figure and the
      probabilities of survival after diagnosis from the AIDS Register of Madrid. This
      methodology was used for Spain as all, and for each Autonomous Community.
      RESULTS: The estimated cumulative incidence of AIDS in Spain by June 1992 was
      16,486 cases, 13.4% greater than that reported by the same date. The prevalent
      cases were 6,351 (95% CI, 5,996-6,708) and the remaining 10,135 (61.5%) would
      have died. This number of deaths is 69.6% greater than the reported figure. There
      were considerable differences among Autonomous Communities. Some of them
      exhibited rates more than six times greater than others. CONCLUSIONS: The
      adjusted estimations provide a view of the actual situation more accurate than
      the raw figures from the register. These great differences should be taken into
      account for appropriate allocation of health care resources.

PMID- 7716408
TI  - [Environmental isolation of Vibrio cholerae 01 in continental waters of the
      Province of Seville].
AB  - BACKGROUND: Many bibliographical references suggest reserves of Vibrio cholerae
      in the aquatic world, strains of both the serovariety no 01 and 01 having been
      isolated in different parts of the globe in fresh and extensive salt waters.
      METHODS: Samples were taken monthly from January to May and from October to
      December, and every fortnight from June to September. The method of isolation
      applied is in accordance with the standard set down by the Institute of Health
      Carlos III, with some specific modifications. RESULTS: During the period 90/91,
      routine analyses carried out by the Andalusian Service of Health of waters from
      the area of the Continental Basin in the province of Seville showed the presence
      of Vibrio cholerae 01. In the same way, during the complete annual cycle Vibrio
      cholerae no 01 was also isolated. CONCLUSIONS: These isolations did not coincide
      with outbreaks or individual cases of cholera, so the authors, in agreement with
      what is described in the bibliography, consider that Vibrio cholerae no 01 forms
      a part of certain aquatic environments, which is in direct relation to
      environmental isolations of the serovariety 01.

PMID- 7716409
TI  - [Hydatidosis control in the province of Rio Negro, Argentina: evaluation of the
      veterinary health care activities. 1].
AB  - BACKGROUND: Hydatidosis constitutes a serious Public Health problem in the
      Province of Rio Negro, Argentine. This situation has promoted the implementation
      of a Control Programme, carried out in 1979. The accumulated experience of 13
      years works is presented in this study. METHODS: The strategy used is that of the
      Primary Health Care; and community participation is a fundamental component of
      the programme as well as local planning and the approach of risk in the
      allocation of resources. The activities included the systematic dogs
      deparasitation with Praziquantel, carried out by health agents from the system
      rural hospitals (health promoters not professional staff); the surveillance of
      dogs rate of infection by means of diagnostic deparasitations made with
      hydrobromide or arecoline, educational talks at schools, the use of mass media,
      an the determination of ovine parasitism in studies carried out in the area
      abattoirs. RESULTS: The information registered indicates that 1,86,156 dog
      deparasitations with Praziquantel were carried out with a consumption of 443,533
      tablets and 11,178 deparasitations with hydrobromide and Arecoline. A continuous
      decrease of rates appears during the Period 1979-1992. So, dog Echinococcosis was
      reduced from 41.5% to 4.24% and ovine Hydatidosis from 61% to 12.7%.
      Consequently, Human Hydatidosis has decreased from an incidence rate of 64.11 x
      100,000 in the age group of 0 to 10 years to and incidence rate of 4.46 x
      100,000. CONCLUSIONS: Finally, the results of the Programme are analyzed in the
      light of other global experiences of control; and the strategies that should be
      put into practice in the future with a view to a final limitation of the rate of
      transmission to man are analyzed.

PMID- 7716410
TI  - [Health behavior of schoolchildren in a metropolitan area of Madrid].
AB  - BACKGROUND: To describe health behavior of students about diet, alcohol and
      tobacco, dental-oral hygiene, leisure time activities and interpersonal
      relations. METHODS: 942 Students have been carried out. Children come from six
      schools of the town of Parla (in the south of Madrid). They are from 9 to 14
      years old. The instruments have been made for this study, helping by teachers of
      EGB. RESULTS: 50% of the students doesn't eat any food at 12 o'clock, after
      drinking a glass of milk only at breakfast (8 o'clock). 10% never eats greens.
      37% of the children in the upper level drinks alcohol sometimes and, in the same
      level, 12% smokes sometimes. Around 25% of children brush their teeth three times
      in the day. The students watch television three hours and half, means, in the
      day. The communication with the teacher is evaluated from "not too bad" to "bad"
      by 70% of the students of upper level. 42% and 39.4% of the children talks about
      abortion and contraceptives, respectively, with nobody. CONCLUSIONS: In general,
      girls have better habits than boys. Only exercise is more prevalent in the boys
      than in the girls.

PMID- 7716411
TI  - [Workplace accidents in health-related personnel in the province of Leon].
AB  - BACKGROUND: To get an initial knowledge about the morbidity by workplace
      accidents in health related personal (hospital and primary attention) in Leon
      province. METHODS: Retrospective study relative to workplace accidents with time
      off work result, in health related personal, in Leon province, for 1990. RESULTS:
      We have observed a rate of workplace accidents in health related personal (31,
      4/1000) smaller than general workers in Leon province (63, 3/1000), Castilla y
      Leon community (44, 7/1000) and Spain (59, 8/1000). The rate in female population
      (37, 4/1000) was higher than the rate in men (21,7/1000). By jobs, the attendant
      an maintenance personal, had more accidents (rate of 118/1000). The most frequent
      mechanism was "fall" (38.2%). The most frequent lesion was "swerve" (38.2%).
      About the part of the body, the most injured were superior members (30.9%) and
      inferior members (30%), 93.7% of workplace accidents were qualified as slight
      accidents. CONCLUSIONS: The health related personal have a lower rate of
      accidents than general workers. The risk of workplace accident is directly
      related with job and place of work. The slight pathological result is most
      frequent.

PMID- 7716412
TI  - [Disability leave due to influenza in the area of Ciudad Real].

PMID- 7716413
TI  - [Toward ordination of health professions].

PMID- 7716414
TI  - [Directives for elaboration of population studies on diet and nutrition. Group of
      Experts].

PMID- 7716415
TI  - [The referral system: a study on relations between general practitioners and
      specialists].
AB  - BACKGROUND: To describe the general practitioners referral patterns. There is
      special emphasis in the delay between the referral and the first consultation
      with the specialist. Also we consider other aspects of the coordination between
      both levels of care. METHODS: Cross-sectional study upon 8.095 referrals from 242
      spanish doctors. RESULTS: The referral rate was 6.63%, higher in the 15-44 age
      group and also for men. We find a huge variability in the referral rates among
      doctors. The referral rates are higher to surgical specialties. The mean delay
      between referral and specialist appointment was 11 days. The general
      practitioners didn't receive communication from the specialists in 23.5 of the
      referrals. CONCLUSIONS: A considerable range of referral rates has been
      identified. There is a poor continuity and coordination in the patient care.

PMID- 7716416
TI  - [Evaluation and improvement of quality during practical training in primary
      health care at health centers of Murcia].
AB  - BACKGROUND: To describe the Public Health in Primary Health Care practice for
      medical students Program objectives, quality of training evaluation method, and
      implementation results. METHODS: 6 learning objectives were designed and training
      implemented in 3 Health Centers in the 90-91 academic course. Evaluation included
      the objectives level of difficulty, and homogeneity in achievement rates between
      objectives, within Centres and between Centres. Evaluation results were analyzed
      and used to design changes to increase homogeneity and achievement rates. Same
      evaluation was performed in the 91-92 academic course to document improvement.
      RESULTS: In the first evaluation there were highly significant differences in
      overall (p. < 0.00005) and by objectives (p. > 0.01) achievement rates between
      centers. Within centres between objectives difficulty was not homogeneous either
      (p. > 0.001). After implementing remedial actions, differences in difficulty and
      achievement rates within and between centres decreased. Increased homogeneity
      affected mostly to two previously less homogeneous objectives. CONCLUSIONS:
      Quality assurance methods can be successfully applied to improve training of
      clearly defined and quantified Primary Health Care learning objectives.

PMID- 7716418
TI  - [Study of temporary disability leave in the City of Jativa].
AB  - BACKGROUND: The study that we present is basically descriptive and contribute to
      try to characterize the morbidity of the insured working population of the city
      of Jativa. METHODS: The period studied is the year 1988. 2044 registers were
      analyzed for cause, sex and duration. The cases were classified according the CIE
      9a. The results are expressed by proportions. The significant differences are
      valued by the Chi-square. The half duration of the process and his interval of
      confidence are studied. RESULTS: The respiratory diseases, with the 32.68%, the
      traumatisms and poisonings, with the 13.36% and the osteomuscular diseases with
      the 11.74% represent the first three causes of ILT. We found differences
      significant in the groups VI (Nervous system diseases) and XVII (Traumatisms and
      poisonings), more frequent for the men, and in the groups V (Mental disorders)
      and VIII (Respiratory diseases) more frequent for the women. CONCLUSIONS: The
      results obtained from the ILT study are important for the knowledge of the of the
      health situation in the city of Jativa.

PMID- 7716417
TI  - [Quality control and results of prevention and health promotion activities in
      infirmary consultations].
AB  - BACKGROUND: To evaluate nursing practice in periodic health examination. METHODS:
      We make a retrospective evaluation of process data through 10 explicit criteria.
      We selected a random sample (in evaluation process) and a institutional based
      sample and population universe (re-evaluation process) of both male and female
      patients who underwent health examination in nursing consults of a urban health
      center. RESULTS: We found a substantial improvement in fulfilling degree in 8 out
      of criteria, although best standard only was reached in 3 criteria (blood
      pressure determination, somatometrics and tobacco smoking investigation). We also
      remark the high proportion of risk factors, tobacco smoking (51.6%), obesity
      (37.6%) and dyslipemia (25.5%). CONCLUSIONS: We remark the importance of entering
      and developing evaluation and quality assurance methodology among common tasks of
      primary care teams and correct ubication of periodic health examination in
      nursing process.

PMID- 7716419
TI  - [Consumption of psychotropic drugs by the aged].
AB  - BACKGROUND: The medical prescription increase for psychotropic drugs, and
      particularly by elderly, are the facts that have motivated this study: 1) elderly
      psychotropic consumption assessment, 2) identify risk factors consumption.
      METHODS: Descriptive and cross-sectional survey from individual questionnaires.
      RESULTS: The prevalence for psychotropic drugs was 24% in our sample, (72.1%
      women). 53.3% prescription were realized by family practitioners. 54.3% patients
      used them for more than three years. The biggest group consumed are the long term
      benzodiazepines (62.3%). CONCLUSIONS: The high prevalence, the long time of
      consumption, the use of long-term benzodiazepines, and the fact of that family
      practitioners are the main prescribers, must make us think about the pertinence
      and accuracy of these medical prescriptions.

PMID- 7716420
TI  - [The triage in disaster medicine: analysis of a practical exercise].
AB  - BACKGROUND: The triage is a procedure for casualties classification using some
      criteria (severity, survival, therapeutical delay, etc.) which is basic for the
      preparedness of health personnel in event of disaster. Even being a basic
      procedure, its teaching and training is not enough extended among health
      personnel. The goal of this study was assess the efficacy of teaching triage
      procedures in terms of its capability to carry out the examination and
      classification of massive casualties under different conditions of environmental
      difficulties. METHODS: 25 couples of health professionals (doctor and nurse) were
      trained during 90 minutes on triage procedures and them aleatory located at 3
      groups with 12 simulated casualties at each group corresponding to 3 different
      levels of environmental difficulties. They were asked to perform the triage and
      complete the information contained at the triage card. This information was
      analyzed in order to see and compare the results of each group. RESULTS: All the
      health professionals showed high correlations between observed and expected
      responses for the evacuation priority variable. However, only the group of less
      environmental difficulty showed a significative statistical correlation (p =
      0.03). No significative statistical differences were found on the diagnostic
      classification but the adjust level was poor for the high environmental
      difficulties group. CONCLUSIONS: Acceptable levels of efficacy on triage
      procedures can be obtained using a single teaching session of theoretical
      contents plus a practical exercise, specially for the casualties prioritization.
      On the other hand, environmental conditions looks as a variable influencing the
      efficacy of other acceptable results expected on this kind of technic perhaps
      requiring further training.

PMID- 7716421
TI  - [Depressive states in sports].
AB  - BACKGROUND: This study was carried out in the Sportive Medical Evaluation Center
      at the Complutense University in Madrid. Its major objective was to assess the
      prevalence of the Depression Status among professional sport men and women.
      METHODS: The Tetradimensional structured Test for depression was used for
      psychometric evaluation to compare two groups of 52 high competition sport men
      and women, and 50 university as the reference group. RESULTS: Study results show
      a 25% prevalence of depression status for the high competition sport group
      compared to a 2% prevalence for the reference group (p = 0.00079). CONCLUSIONS:
      These results seem to conform the association between high competition sport
      practice and the occurrence of depressive status.

PMID- 7716422
TI  - [The Contract Program: What is it? What is its importance?].

PMID- 7716424
TI  - [Assessment of health needs of the aged].
AB  - The increase of ancient population constitutes a challenge for society in general
      and for the health services in particular in relation with the offer planning and
      adequacy. It is important to know the health needs and status of our old people
      population to determine the intervention priorities and, on the other part, to
      measure the programmes efficiency and efficacy. As years go on, body organs get
      old in a different way, which leads to individual variations in the speed of
      organs and systems deterioration; that is why, a reasonable good scale of and
      overall health does not exist in contrast with functional status and
      psychological health. Certain cultural attitudes towards aging and the health
      care resources availability make measurement more difficult, as well. For all
      elaborated with and overall point of view, by means of a systematic search of
      problems and a total valuation of his health needs.

PMID- 7716423
TI  - [Tobacco, equity and primary health care].
AB  - BACKGROUND: Antitobacco campaigns in industrialized countries (USA, Canada,
      United Kingdom, Sweden, Finland, Australia) have been less effective FOR low
      social classes, except for Australia. In order to attain further reductions of
      tobacco consumption, these countries have to pay attention to tobacco use amongst
      people of low socioeconomic status. This paper seeks to analyze the causes of it
      to summarize relevant lessons for our own country. METHODS: Literature review in
      relation to tobacco consumption, social status, mediating variables between these
      two elements, and variety of possible interventions. RESULTS: Low social classes
      bear higher tensions, more compelling economic, familiar, affective and social
      relations problems, with a lower capability to adapt, neutralize or change their
      situation; therefore making their emotional dependence on tobacco, stronger.
      Family physician's intervention and community participation appear as the
      recommended alternatives to mass-media public campaigns. CONCLUSIONS: These two
      interventions should be fostered through the national Primary Health Care
      Network, as a complement to public campaigns, to guarantee in equity in reducing
      tobacco consumption and its consequences.

PMID- 7716425
TI  - [Experience of the British health care system reform after the 1989 White Book
      and its possible application for the rational use of pharmaceuticals in Spain].
AB  - BACKGROUND: The analysis of the different governmental actions taken by the UK to
      rationalise the use of pharmaceuticals and the possibility of applying this
      rationales and method in Spain. METHODS: International and British literature
      were reviewed before a personal visit interviewing British health professionals
      on the central, regional and district level. Particular attention was given to
      the evaluation of and or information on generic drugs; the Indicative Prescribing
      Scheme and the Prescribing Analyses and Cost (PACT); the new roles of medical and
      pharmaceutical advisers for Primary Care prescriptions; the new "Medical Resource
      Centres" (MeReC) and "Medical Advisers Support Centre" (MASC); the role of the
      pharmacist in the hospital and community pharmacy is also analysed. RESULTS: The
      British approach has improved prescription use and patient care and has helped to
      discipline uncontrolled growth in pharmaceutical expenditures. CONCLUSIONS:
      Similar measures can probably be implemented in other health systems,
      independently of whether or not the basic principles behind the reformed British
      system which are still unproven over the long run are adopted.

PMID- 7716426
TI  - [Nutritional factors and geographic differences in pancreatic cancer mortality in
      Spain].
AB  - BACKGROUND: The relationship between diet and cancer of the pancreas was assessed
      in a ecological study by calculating the intakes of foods and nutrients in the
      different Spanish provinces, during the period 1964-65, and relating these to the
      provincial pattern of death from pancreatic cancer 20 years after (1984-86).
      METHODS: The geographical pattern of mortality was evaluated by calculating the
      Standardized Mortality Ratios (SMR) for each province. Intake of foods was
      obtained from the National Institute of Statistics. Nutrients intakes were
      calculated from these consumption figures, by reference to tables of food
      composition. Simple and multiple linear regression studies with these variables
      were carried out. RESULTS: Regression coefficients obtained with foods and
      nutrients in the univariate analyses were in general low. In the separate
      multivariate models, consumption of milk and cheese were constantly positively
      correlated with pancreatic cancer mortality rates in males. For females,
      consumption of eggs was positively associated, and fruit consumption was
      negatively correlated. Analyses of nutrient intake adjusted for total energy
      showed that proteins were the most strongly correlated of the variables
      considered in both sexes. Animal fat, cholesterol and saturated fat were
      statistically significant positively correlated with pancreatic cancer mortality.
      CONCLUSIONS: The results obtained are consistent with the hypothesis that diet
      can play a role in the etiology of the cancer of the pancreas. Further studies
      are needed to obtain empirical evidence for (or against) the associations found.

PMID- 7716427
TI  - [Program of early detection of breast cancer in Castilla-la-Mancha. Preliminary
      data of the first 5 months of performance. Regional Group on the Evaluation of
      the Program of Early Detection of Breast Cancer].
AB  - BACKGROUND: A Breast Cancer Screening Programme managed by the Regional Ministry
      of Health in Castilla-La Mancha (Spain) was started in November 1992 in two
      districts. The purpose of this study is to describe the short-term results after
      five months of running. METHODS:  DESIGN: descriptive, cross-sectional study.
      SETTING: female population of Talavera de la Reina and Cuenca cities, from
      November 1992 to the end of March 1993. PARTICIPANTS: 10.050 healthy women
      between 45-64 years old, who were invited, by personal letter, to attend a
      mammography unit. RESULTS: 6.503 women accepted the screening invitation
      (participation rate of 65%) without differences between both districts. The
      personal letter was the main information source to women, and the presence of
      beliefs, attitudes and favorable experiences were the main reasons to accept the
      screening. The rescreening was needed by 4% of women, and finally, 67 women
      (1.1%) were classified "positive". The programme cost for every women into the
      screening was 4.067 ptas. CONCLUSION: According to these results, is it feasible
      as economically as from the point of view of the organization, to extend the
      programme in Castilla-La Mancha.

PMID- 7716428
TI  - [Age of menopause onset in Canary Islands women].
AB  - BACKGROUND: To establish the age at menopause in the Canary woman. To study the
      possible influence of habitat, socioeconomical status and other possible factors
      on it. METHODS: From an initial population of 742 women, we previously excluded
      those that were not menopausal at the moment of the study and those that suffered
      it as a result of a oophorectomy. We included 394 women that had a natural
      menopause in the study group. RESULTS: The mean age of menopause was 48.6 years
      old. There were no statistical differences between the natural or urban areas.
      Neither the age of menarche nor the number of pregnancies had any influence on
      the age of menopause. Women with high socioeconomical status had the menopause
      later (50.7 years old) than hose with medium or low socioeconomical status (48.6
      and 48.4 years old respectively). DISCUSSION: Comparing the age of menopause
      found in our study (48.6 years) with the published in other papers, this is very
      similar to the age mean reported in other spanish studies but a little lower than
      the age of menopause established in some occidental countries.

PMID- 7716429
TI  - [Evaluation of ELISA and double diffusion (DD5) test in the diagnosis of human
      hydatidosis in asymptomatic population].
AB  - BACKGROUND: The early diagnosis of Human Hydatidosis through immunologic methods
      has been one of the most important activities displayed by the Programme of
      Struggle (fight) in endemic areas of Argentina, to improve the prediction of the
      Hydatid patient. It is of great interest to define exactly the advantages and
      limitations of the DD5 and Elisa techniques in the diagnosis of hydatidosis in
      inhabited areas with no clinic symptoms of the disease. METHODS: For this, the
      sensibility, the specification and predictive value of both methods has been
      evaluated, studying serologically 499 inhabitants from a rural community in the
      Province of Rio Negro. The inhabitants with reactive serology to EIE and/or DD5
      are studied by means of images using US, RX and TC. A controlled group is
      selected according to its un-reactive serology. The cases compatible with
      Hydatidosis are directed to surgery. RESULTS: The DD5 technique is shown as 100%
      specific but with a sensibility of only 31%; on the other hand, EIE at a cutting
      level of 8 DE presents a specification of 97% with a sensibility of 63%.
      CONCLUSIONS: It is important to underline the value of the US as the first image
      prognosis, while the TC, in the present experience, did not show a great number
      of positive images, allowing only to confirm the US findings.

PMID- 7716430
TI  - [Infestation by Giardia lamblia of children in the basic health area of East
      Rural Avila].
AB  - BACKGROUND: GIARDIA LAMBLIA (GL) constitutes a problem of public health
      especially (because of its greater frequency) amongst children. The aim of this
      study is to determine the prevalence of GL amongst children in the ZONA BASICA DE
      SALUD (ZBS) in the eastern part of the province of AVILA. METHODS: An
      observational prospective study undertaken in the ZBS of the eastern part of the
      Province of Avila during the 1992-93 school year. The faeces of 318 children,
      aged 3 to 14, without symptoms, attending school in 8 villages of the area were
      studied by means of the Teleman-Rivas test. RESULTS: The over all Prevalence of
      GI is 4.4%, we found no statistically significant differences between girls and
      boys, or between children aged over or under 10, or between those living in
      villages with more or fewer than 2000 inhabitants. CONCLUSIONS: The prevalence of
      GL amongst the child population of ZBS in the eastern part of the province of
      Avila is 4.4% which figure accords closely with those found in similar studies.

PMID- 7716432
TI  - Swedish Association of Urology. Proceedings of the annual meeting. Stockholm,
      November 30-December 2, 1994. Abstracts.

PMID- 7716433
TI  - [Biological monitoring of the water supply].

PMID- 7716431
TI  - [A coprological study of intestinal infections in Northern Morocco (provinces of
      Tangier, Tetuan and Larache)].
AB  - BACKGROUND: An epidemiological study on intestinal parasites has been carried out
      in Northern Morocco (province of Tangier, Tetuan and Larache). A comparative
      Study has been made at a provincial, city and areas (urban and rural) level. Also
      the SPI (simple parasitism index) and the CPI (comparative parasitism index)
      distribution. METHODS: The coprological method used were: direct, concentration
      (Fulleborn, Telemann and Kato) method and ye test technics (Ferric Hematoxylin
      and E. Chlorazol Black). RESULTS: The number of faecal samples were 4643,
      parasitism people 2637 and the total number of parasites were 4816. SPI 56.79%
      and CPI 1.83. Among the Protozoa, Entamoeba coli, followed by Endolimax nana,
      Giardia lamblia and Iodamoeba buetschlii prevailed, the other species coming a
      lung distance behind. Among the Helminths, Trichuris trichiura prevailed much
      more than the others; Ascaris lumbricoides followed and on the third place were
      Enterobius vermicularis and Hymenolepis nana. The percentage found for E.
      vermicularis was very high, since an appropriate technique of diagnosis was not
      used. The data have been statistically tested. CONCLUSIONS: We found a high rate
      of parasitism in the 3 provinces that have studied and an approximate number of
      two parasites per person. SPI and CPI are greater in Tetuan and Larache than in
      Tangier.

PMID- 7716434
TI  - Sex differences of infant and child mortality in China.
AB  - The purpose of this paper was to study the sex differences in infant mortality
      and mortality before the age of 5 in China, and the differences between urban and
      rural areas on the one hand and urban areas of mainland China and Hong Kong on
      the other. Published data from the 1982 and 1990 national censuses, the mortality
      survey of 1976, and UN's publications were used to calculate sex differences and
      sex ratios of mortality. Infant mortality of both sexes decreased notably from
      the 1970's onwards, the sex ratios of mortality being 1.15 in 1973-75, 1.06 in
      1981 and 0.86 in 1990. A remarkable decline of mortality before the age of 5 was
      also seen in both sexes, but the sex ratios of mortality were not greatly
      altered, remaining less than 1 from the 1970's on. In rural areas female infants
      and young children had a higher mortality compared with males than in urban
      areas. In Hong Kong, the sex differences of infant and early child mortality were
      much smaller than in urban areas of mainland China.

PMID- 7716436
TI  - Population based CVD health risk appraisal. A method to create a "critical mass"
      of health-conscious people.
AB  - This study used a population based screening procedure as a means for a combined
      strategy for targeting individuals at high risk of cardiovascular disease while
      aiming for a low-risk population. During a five month period 68% of the total
      target population (2642 out of 3880) men and women attended the screening. We
      found, 1) that a broad population based health risk appraisal activity, supported
      by a personal computer as an educational tool and as a means to speed up the
      handling of each test, was feasible, 2) that it was easy to identify high risk
      individuals, to be able to offer them further follow-up, and 3) that there is
      evidence supporting the view that reaching a large proportion of the population
      in a limited time period, a "critical mass", will contribute to a growing health
      awareness not only among participants but also among the general population in
      the actual area.

PMID- 7716437
TI  - A study of men aged 33-42 in Habo, Sweden with special reference to
      cardiovascular risk factors. Design, health profile and characteristics of
      participants and non-participants.
AB  - An intervention study of men living in the Community of Habo in southwestern
      Sweden has been carried out. All men aged 33-42 and living in the community were
      invited. Altogether 652 men participated. The study included a questionnaire, an
      interview made by a nurse, anthropometric measurements, blood pressure
      measurements, measurements of respiratory function and work performance capacity,
      and blood sampling for chemical analyses. The participation rate was high, 86.1%,
      after one mail invitation even considering the fact that two reminders were sent.
      Most of the non-participants had recently been in contact with the health care
      organisation, either because they were high-consumers of health care, or because
      they had attended a health examination at work. A health profile was worked out
      comprising 11 different potential risk factors for coronary heart disease. This
      health profile turned out to be a useful educational tool when discussing the
      results of the examination with the participants. Risk points were given
      according to certain predetermined criteria. The distribution of risk factors was
      similar in the different ages studied. Most of the participants had at least one
      risk factor as defined, but many of them had two or more risk factors.

PMID- 7716435
TI  - Death rates and causes of death among children and youth in Goteborg, Sweden 1971
      85. Indicators for public health work in a city.
AB  - Among children and youth in Goteborg, Sweden, the death rate per 100,000 children
      decreased from 32 in 1971-75 to 24 in 1981-85 and in youth from 76 to 54.
      Accidents and human violence together with tumours and congenital malformations
      remained the most important causes of death in children, together accounting for
      2/3 of all deaths. A marked decrease in traffic accident deaths among children
      and young people is an encouraging result of prevention. Among young people human
      violence (mainly suicide) emerged as the most important cause of death relative
      to other causes of death. Alcohol-related mortality was also a notable cause of
      death in this age group. Preventive measures directed against human violence and
      alcohol-related mortality should be the subject of consistent and sustained
      committment to action comparable to that applied over many years to traffic
      accidents.

PMID- 7716438
TI  - Mortality from stroke, coronary heart disease and all causes related to blood
      pressure and length of follow-up.
AB  - Measurements of blood pressure in 52,064 men and women in the city of Bergen,
      Norway, who were 30 to 89 years in 1963, have been related to mortality occurring
      in different intervals of the follow-up period from 1963 throughout 1983. Blood
      pressure measurements obtained on one occasion were highly predictive of both
      coronary heart disease, stroke and all-cause mortality several years after
      measurements. The relative risk of stroke mortality associated with blood
      pressure varied little in the first ten to fifteen years, but the predictive
      power was clearly lower in the last five years of follow-up. The relative risk of
      death from coronary heart disease was stable in the whole period of follow-up.
      The risk curves relating coronary heart disease mortality to diastolic blood
      pressure in men and women aged 60-79 years at screening had the same shape in the
      first five years as in the rest of the follow-up. No J-shaped association was
      seen in either time interval.

PMID- 7716439
TI  - The Johanneberg study--a sociomedical survey in an urban elderly population. I.
      General presentation of the study including an analysis of non-response and
      identification of risk groups.
AB  - This study is the Swedish part of a world-wide transcultural and
      interdisciplinary study in elderly populations which addresses food habits,
      health and life-style. The aim of this paper is to present the general design
      including an analysis of non-response, and to identify risk-groups for
      intervention programmes. The study comprised 217 noninstitutionalized males (n =
      73) and females (n = 144), aged 70 and over (mean age 78 years) in a small urban
      area. Home visits and clinical examinations with standard methods were used. The
      participation rate was 76%. Significant differences between non-respondents and
      respondents could be seen, which may be important when planning health promotion.
      On the basis of experiences during the examinations, a risk-group was identified
      for prospective and intervention study purposes, based on a multiple variable
      model and a clinical model.

PMID- 7716440
TI  - An economic appraisal of two strategies in geriatric screening.
AB  - Screening for preventive geriatric health-care has become common in many
      Norwegian municipalities. Different methods are used to screen for unreported
      need of intervention. There is little information available about which is the
      most costeffective method. This article describes a comparison of two screening
      models. The first screening was conducted by means of a personal interview held
      at a health clinic and the second by a postal questionnaire. The results show
      that a postal questionnaire study was more cost-effective than the health-clinic
      consultation. It demanded no more resources than the health-clinic model, but had
      a wider effect because it covered a broader spectrum with regard to response,
      proportion of the total population and the proportion of respondents for whom an
      intervention was implemented.

PMID- 7716441
TI  - Psychosocial consequences of traffic accidents: a two year follow-up.
AB  - The aim of the study was to assess long term outcome of injuries from traffic
      accidents with focus on psychosocial aspects. Eighty-four persons injured in
      traffic accidents and with moderate to severe injuries (ISS > or = 9) were
      interviewed approximately two years after the accident. We examined psychosocial
      consequences within eight different domains; sequelae of the injury,
      psychological consequences, sickness compensation received, living conditions,
      need of assistance, working capacity, economic situation and leisure time
      activity. Sixty-eight percent of the persons reported that they still suffered
      from physical seqelae and 57% had been or were still suffering from psychological
      distress after the accident. Sixty-three percent were on the sick-list for at
      least three months because of the accident. Fifty-eight percent needed some type
      of handicap aid during some time after the accident. For 29% of the
      professionally employed the traffic accident led to changed working conditions.
      The study indicates a need not only for adequate medical treatment, but also
      psychological and social counseling in the rehabilitation of victims of traffic
      accidents. Resources for crisis intervention should also be available at an early
      stage.

PMID- 7716442
TI  - Exercise tolerance and work ability following aorto-coronary bypass surgery.
AB  - This investigation was performed to study the reasons for receiving disability
      pension after aortocoronary bypass surgery. During the period March 1983 to
      November 1985, 250 patients underwent aortocoronary bypass surgery. At a mean
      follow-up of 4.9 years (range 3.6-6.7) after the operation, 31 patients were
      dead. Of the 219 survivors, all except four underwent a follow-up examination
      including an exercise test. The mean physical work capacity had increased from
      92.2 W preoperatively to 119.3 W at follow-up (p < 0.001). At follow-up, however,
      72 patients had received disability pension. The percentage of positive ECG-tests
      were equal among those who were working and those who had received disability
      pension. We suggest that, among those who had received disability pension, about
      50% were in sufficient physical condition to manage their previous jobs or
      another type of job. Reasons other than physical working capacity played an
      important part as criteria for receiving disability pension.

PMID- 7716443
TI  - A comparison of the progression rate to acquired immunodeficiency syndrome
      between intravenous drug users and homosexual men.
AB  - In order to study differences in progression to Acquired Immunodeficiency
      Syndrome (AIDS) between risk groups, 205 homosexual men and 185 intravenous drug
      users (IVDUs) were followed from diagnosed seropositivity for Human
      Immunodeficiency Virus Type-1 (HIV) for a mean period of 46 months (range 1-88
      months). Seven (4%) IVDUs and 55 homosexual men (27%) were diagnosed with AIDS
      during the follow-up period. The probability of being AIDS-free four years after
      diagnosed HIV positivity was 0.96 for IVDUs (SE 0.02) and 0.73 (SE 0.04) for
      homosexual men (p < 0.001, log rank test). When controlling for age and gender,
      the relative risk of AIDS progression for homosexual men was 9.1 (3.5-24.1, 95%
      confidence interval) as compared with IVDUs. Even when 24 months of follow-up
      time without progression were added for all homosexual men, assuming that the
      epidemic started two years earlier in this group, the relative risk of
      progression was 5.4 (2.1-14.4, 95% confidence interval) for homosexual men.

PMID- 7716444
TI  - Institute "Jakes"--an experiment which ceased to exist.
AB  - Institute "Jakes", which sheltered psychiatric patients, was apparently the most
      unorthodox part of the health care delivery system in the former Yugoslavia.
      Bosnian war led to severe destruction of the Institute and to death of many of
      its patients. The "Jakes" experience deserves attention and description.

PMID- 7716445
TI  - [Congenital toxoplasmosis].

PMID- 7716446
TI  - [Parasitology and human medical preventive importance of Toxoplasma gondii].
AB  - Present knowledge of the biology and distribution of Toxoplasma gondii allows to
      provide recommendations for primary prevention of infection with the parasite.
      The recommendations are chiefly designed for "seronegative" pregnant women
      without specific serum anti-T.-gondii-IgG and for persons with continuous or
      temporary immune deficiencies. Prevention should focus on 3 main sources of
      infection risk: Meat: meat should only be eaten when well cooked or when it has
      been frozen prior to preparation; do not prepare raw food in the same place and
      with the same utensils as for raw meat preparation; no mouth-finger-contact while
      handling raw meat. ENVIRONMENT: fruit and vegetables should be carefully washed
      prior to consumption (also including fruit and vegetables from the consumer's own
      garden or orchard). Cats: household cats should be preferably fed with canned
      food rather than with raw meat; contact with any utensil which may have been
      contaminated by cat's feces, as well as with the cat's litter, must be strictly
      avoided. If cleaning the cat's toilet is inevitable, plastic gloves must be worn.
      Disinfect the cat's toilet daily with boiling water. All primary prevention
      measures apply also to the areas of agriculture, veterinary practices, pet shops
      and gastronomy. Secondary prevention by means of serological monitoring of
      seronegative pregnant women can only be envisaged when associated with precise
      primary prevention recommendations.

PMID- 7716447
TI  - [Cost-benefit analysis of screening for congenital toxoplasmosis].
AB  - A comprehensive cost-benefit analysis of possible screening strategies for
      congenital toxoplasmosis is necessary as a basis for the decision whether or not
      screening is efficient and socially desirable. The total costs of the disease in
      Switzerland were calculated for the year 1990. Direct costs (all diagnostic and
      therapeutic interventions, including care of handicapped children) and indirect
      costs (partial and total work losses in the future) were taken into account.
      Today, the direct costs amount to approx. SFr. 20 mio per year (i.e. approx. SFr.
      2.8 mio per million population). The indirect costs were calculated at SFr. 4 mio
      per year. Moreover, the costs incurred with three possible screening programs (1
      test with all pregnant women, with 1, 2 or 5 additional tests, depending on the
      strategy) were estimated, together with the concomitant cost savings. The
      financial resources needed for the screenings would amount to SFr. 7 mio-18 mio
      per year, depending on the strategy chosen. However, the possible savings would
      be in the range of SFr. 4 mio-12 mio only. The possible savings are, in any case,
      of the same order of magnitude as the costs for screening. Screening would become
      cost-efficient if costs for the serological tests could be lowered.

PMID- 7716448
TI  - [Prevention of congenital toxoplasmosis in Switzerland. Consensus report of the
      study group "Congenital toxoplasmosis" of the federal public health office].

PMID- 7716449
TI  - [Epidemiology of toxoplasmosis: worldwide status].
AB  - A literature review of toxoplasmosis seroprevalence data available over the last
      40 years has been conducted both among European women of reproductive age and
      general populations at the global level. Summary maps are presented. In Europe,
      the highest seroprevalences have been reported from France, both among women of
      reproductive age and the general population. There is a higher seroprevalence in
      Central Europe than in Scandinavia or the United Kingdom. At the world level,
      prevalences similar to those of Central Europe have been reported in sub-Saharan
      Africa and Latin America. Lower prevalences are found in North America, South
      East Asia, and Oceania. The limitations of such comparisons are discussed.

PMID- 7716450
TI  - [The status of infection with Toxoplasma gondii in the Swiss population:
      contribution of a seroepidemiologic study from the Zurich canton].
AB  - To obtain information on the seroprevalence of specific antibodies to Toxoplasma
      gondii at the level of the general population, a study was performed using 4300
      serum samples: 3500 samples collected at the blood donor center of Zurich
      (individuals between 18 and > 65 years old), 500 serum samples from children
      referred to the University Children's Hospital of Zurich (between 1 month and 17
      years old) and 300 maternal sera, collected at delivery (from a mother-child sera
      collection of the University Children's Hospital of Zurich). Samples were
      systematically collected by age- (5 years) and sex-groups (sex ratio 1:1), until
      the desired number was obtained. The crude seroprevalence of specific IgG anti-T.
      gondii was 52.4% (confidence interval at 95% [p < 0.05]: 50.9-53.9). There were
      no significant differences between males and females. The seroprevalence of the
      group of women of childbearing age (between 20 and 40) was 40%. The comparison of
      this value with the results obtained from 300 maternal sera from the mother-child
      collection revealed no significant difference between the two groups. On the
      basis of these results and assuming that the information obtained at the level of
      the general population in the region of Zurich is representative of Switzerland,
      it was possible to calculate the required sample size to initiate a national
      study on seroprevalence of the infection with T. gondii among women at time of
      delivery.

PMID- 7716451
TI  - [Epidemiology of toxoplasmosis in Switzerland: national study of seroprevalence
      monitored in pregnant women 1990-1991].
AB  - A national study was performed to assess the seroprevalence of anti-Toxoplasma
      gondii IgG in pregnant women at the time of delivery. The study was organized
      between 1990 and 1991 in 23 out of 26 Swiss cantons. 9059 women, corresponding to
      11.8% of the annual total of births in those cantons, were included. The global
      seroprevalence of specific IgG was 46.1% (95% confidence interval: 45.0-47.1%).
      There was no significant difference in seroprevalence between different cantons
      after adjustment according to age. At the national level, the seroprevalence was
      46.0% for Swiss women and 45.8% for women of other nationality (information on
      nationality was available only for 8382 persons). The use of a model of linear
      regression according to age showed that the risk of seroconversion among
      seronegative women during their 9 months of pregnancy was 1.21%. In addition, a
      certain number of data were calculated from that value to "simulate" a
      theoretical situation with absence of specific serological screening during
      pregnancy at a national level and consequently, absence of appropriate treatment.
      It was estimated that 548 cases of seroconversion would occur annually during
      pregnancy. This would lead to 183 congenital transmissions of toxoplasmosis,
      among which, 75% would be asymptomatic at birth. The number of expected
      pathologies would be: 40 cases of chorioretinitis with impared vision, 18 cases
      of cerebral lesions, and 2.7 cases of perinatal death. We observed positive
      results for specific anti-T. gondii-IgM in 1.7% of persons tested. This result
      can be the source of medical interpretation difficulties if the serum sample is
      the first done during pregnancy.

PMID- 7716452
TI  - [Biological diagnosis of toxoplasmosis in the course of pregnancy: methods,
      interpretations and practical recommendations].
AB  - The biological diagnosis of infection with Toxoplasma gondii during pregnancy can
      be performed: either (1.) with direct methods (microscopic examination, in vitro
      isolation on cell cultures, histology, detection of T. gondii DNA) or (2.) by
      indirect serological methods in order to demonstrate specific antibodies in
      serum. An appropriate combination of complementary techniques (antibody detection
      in serum and demonstration of the parasite) must lead, in the majority of cases,
      to a precise diagnosis of congenital toxoplasmosis. Serological examination of a
      woman before or at the beginning of pregnancy serves to distinguish between women
      with or without specific immune status. The diagnosis of a seroconversion during
      pregnancy causes few difficulties particularly if carefully followed up. However,
      it is rather difficult to date an infection during pregnancy based only on a
      initial positive sample with the presence of anti-T. gondii IgM. Thus, around 1
      to 5% of serological examinations during pregnancy cause practical problems of
      interpretation. A certain number of recommendations are suggested to the
      laboratory supervisor: 1. Pregnant women should be systematically tested for
      specific anti-T. gondii IgG or total Ig and IgM. The choice of the techniques
      serves to reliably distinguish women without anti-T. gondii antibodies (women at
      risk for primary infection) from those with anti-T. gondii antibodies (immune
      women). 2. Interpretations of results should be well formulated to be
      understandable to the practitioner who must adequately inform the patient and
      determine the proper medical action on the basis of the serological results. 3.
      Sera should be preserved systematically for a minimum of 12 months (whatever the
      results may be). 4. Cases or situations causing problems should be referred to a
      specialized laboratory for expert advice.

PMID- 7716453
TI  - [Should a preventive congenital toxoplasmosis program be established in
      Switzerland?].
AB  - The Swiss Federal Office of Public Health established a multidisciplinary working
      group whose objectives were to review the subject of congenital toxoplasmosis
      (CT), to strengthen, as far as possible, the level of knowledge concerning
      congenital toxoplasmosis in Switzerland (particularly the epidemiological and
      economic aspects) and to propose a CT prevention programme acceptable to all
      concerned medical disciplines. Two main questions were considered: (1.) Does the
      size of the congenital toxoplasmosis problem justify the cost of a systematic
      screening programme for pregnant women? (2.) How secure is laboratory diagnosis?
      Neither the national system of reporting by laboratories and physicians,
      mortality statistics nor insurance records are adequate to estimate the incidence
      of congenital toxoplasmosis. A study carried out at the main hospital departments
      of neonatology and pediatrics in Switzerland provides a more accurate estimate
      but does not match the number of cases predicted by mathematical models. The
      discrepancy does not put the seroprevalence studies in doubt but rather the
      estimate of the rate of transmission of T. gondii to the fetus and its degree of
      virulence. The implementation of a better surveillance system would provide
      information for adoption and funding of a prevention programme based on facts
      rather than estimations. Those who support a generalized screening programme for
      pregnant women must also make an effort to convince the community of its
      importance. A prenatal screening programme for pregnant women should resolve
      problems rather than create new ones. The security of the diagnosis of an
      infection and the effects to the fetus are of vital importance for the principle
      primum nil nocere.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716454
TI  - [Current diagnostic aspects of toxoplasmosis].
AB  - Biological diagnosis of toxoplasmosis is now based more widely on combined use of
      serology and techniques for detection of the parasite or its constituents.
      Serologic methods endeavour to describe more reliably the antibodies involved in
      the humoral response and define their specific antigenic properties. Use of
      purified parasite proteins and characterization of isotypes having short-lived
      kinetics now make it possible to be more precise about the date of contamination
      in the case of first infections; however, serology remains of limited interest
      for diagnosis of toxoplasmosis in immunodepressed patients. Techniques for
      detection of the parasite by cell culture, or of parasite DNA by polymerase chain
      reaction, now represent the alternatives of choice to direct search or animal
      inoculation. These techniques are more specifically indicated where the immune
      response is abnormal or absent, particularly in immunodepressed patients and in
      the fetus. The results, obtained in a few days, provide a reliable diagnosis and
      enable specific treatment to be instituted.

PMID- 7716455
TI  - [Toxoplasmosis in pregnancy: prevention, prenatal diagnosis and treatment].
AB  - Maternal infection with Toxoplasma gondii acquired during pregnancy occurs in
      more than 500 women per year in Switzerland. Systematic screening at the
      beginning of pregnancy allows the introduction of health education programs. The
      screening during pregnancy is performed to diagnose primary maternal infections
      and to propose prenatal diagnosis and treatment. The administration of specific
      antibiotherapy during pregnancy (spiramycine or the association of pyrimethamine
      and sulfonamides) significantly reduces the risk of fetal infection. Prenatal
      diagnosis of congenital toxoplasmosis is possible and reliable. It avoids
      unnecessary termination of pregnancy when the fetus is not infected and specific
      therapy in case of infection (association of pyrimethamine and sulfonamides).
      Prenatal treatment may be proposed without prenatal diagnosis as of the 16th week
      of gestation. In any case, prenatal treatment seems to reduce the incidence of
      severe congenital toxoplasmosis.

PMID- 7716456
TI  - [Congenital toxoplasmosis: pediatric approach. Consensus report of the Swiss
      infectious disease pediatricians].
AB  - The first part of this paper reviews: (1) the spectrum of clinical features of
      congenital toxoplasmosis; (2) the natural course of fetal infection; (3) the
      influence of antitoxoplasma therapy on the course of the disease; (4) methods for
      diagnosing the toxoplasma infection and assessing the severity of the disease;
      (5) currently used antitoxoplasma drugs and different therapeutic regimens. The
      second part suggests a practical approach to the problem of congenital toxoplasma
      infection, including diagnostic work-up, drug therapy, and follow-up. This
      practical approach is modulated according to the clinical syndrome in the infant
      and diagnostic and therapeutic considerations in the mother.

PMID- 7716457
TI  - [Toxoplasmosis and ocular pathology].
AB  - Toxoplasmosis is the leading cause of posterior uveitis in the immunocompetent
      adult, and potentially leads to blindness. Ocular Toxoplasmosis is usually
      considered a recurrence of a congenital infection, and this fact enhances the
      importance of prevention in pregnant women in order to avoid transplacental
      passage of free forms of the parasite Toxoplasma gondii. Ocular toxoplasmosis can
      also be acquired following undiagnosed primary infection in immunocompetent or
      immunodeficient patients, particularly AIDS patients for whom it indicates a
      modification of the immunologic pattern. The typical ocular lesion is necrotizing
      retinitis, satellite of an existing scar, whose situation in the fundus of the
      eye, number, size, aspect and evolution are variable; more rarely, ocular
      toxoplasmosis presents in other forms (anterior uveitis, pars-planitis,
      scleritis, papillitis). The treatment of ocular toxoplasmosis, remains
      controversial, in particular due to drug side effects. This enhances the
      importance of alimentary and environmental prevention.

PMID- 7716458
TI  - [Toxoplasma gondii: perspectives for a vaccine].
AB  - To date no single vaccine has been commercialized in the field of human
      parasitology, and therefore a practical approach to a potential Toxoplasma
      vaccine in the field can only be discussed theoretically. The aim of such a
      vaccine would consist either in inhibiting endogenous parasite multiplication
      (tachyzoite formation) and thus dissemination, or in preventing the final
      formation of Toxoplasma cysts (bradyzoite formation). Immune protectivity should
      confer resistance to disease and parasite dissemination in pregnant women, in
      order to prevent congenital toxoplasmosis in the unborn infant, and prevent cyst
      formation in order to avoid reactivation in case of future immunosuppression of
      the individual. The establishment of a successful protective immunity was
      elucidated in the mouse model: the number of formed Toxoplasma cysts is primarily
      regulated by the function of Toxoplasma-specific CD8(+)-T-cells. Direct effector
      functions of cytotoxic CD8+ lymphocytes directly depend on local periparasitic
      gamma-interferon- and TNF alpha-concentrations. Immunological aberrance occurs if
      locally (cerebral) synthesized Il-10 and Il-6 induce anergistic
      immunosuppression. An experimental vaccine in the mouse demonstrated primary
      dependence of a protective immune response on CD8+ and CD4+ (Th) cells.
      Experimental vaccines within domestic animals concentrate mainly on the
      development of temperature-sensitive mutants of the T. gondii RH-strain, which
      will protect animals from disease but not from infection and cyst
      formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716459
TI  - [Prevention of congenital toxoplasmosis in Europe].
AB  - To sound out prevalent opinions among health authorities in Europe concerning the
      control and prevention of congenital toxoplasmosis (CT), a questionnaire was sent
      to the 28 WHO member countries in Europe. The questionnaire was returned by 23
      countries. Only 7 countries recommend systematic screening of pregnant women. The
      reasons given by the 14 countries which do not recommend systematic screening are
      diverse: recommendations are in preparation, unfavourable cost-benefit return,
      absence of satisfactory treatment, programme not possible, incidence level too
      low, etc. 11 countries have a surveillance system for CT, of which only 3 are
      among the countries which recommend systematic screening. However, the absence of
      a multidisciplinary approach does not permit proper surveillance of cases. It
      appears from this survey that control of CT is undertaken in a very heterogeneous
      manner in Europe and no country has a programme whose impact on CT can be
      measured. So far, the European experience does not permit conclusions either in
      favour of or against a programme for the systematic screening of CT. However,
      cost-benefit analysis plays a very important role in determining whether such a
      programme should be implemented. Parameters such as the security of diagnosis
      (standardization of methods, quality and experience of the laboratories) and the
      monitoring of cases (definition, multidisciplinary approach to the surveillance
      and long-term treatment of patients, national collection of case reports,
      evaluation of the programme) are indispensable for the implementation of an
      effective surveillance system.

PMID- 7716460
TI  - [Help becomes self-help].

PMID- 7716461
TI  - Bonded to tooth ceramic restorations: in vitro evaluation of the efficiency and
      failure mode of two modern adhesives.
AB  - Dentinal seal and the internal adhesive interface of bonded tooth ceramic
      overlays were evaluated in vitro, using a dye infiltration test and direct
      indirect SEM observations. The new adhesives such as Optibond or Scotchbond MP
      demonstrated better performances in dentin bonding than former adhesives. With
      the large cementing space (300 microns), a rigid set-up restraining compensatory
      phenomena between the restoration and the tooth proved again to negatively
      influence the dentinal seal of bonded ceramic overlays. In the present test
      conditions, dentin bonding of the new adhesives remains perfectible, even if the
      total etch technique is applied. Failure modes of Optibond and Scotchbond MP
      showed some specific features. For both brands, bonding failures occurred mainly
      between the hybrid layer and the overlaying resins; these are not of an
      artefactual nature, as was demonstrated by indirect SEM observations. The
      cohesiveness of the adhesive interface does not appear optimal at the present
      time; the need for stress reduction in the cementing space therefore remains of
      primary concern in dentin bonded restorations.

PMID- 7716462
TI  - [Cariogenic carbohydrates in maltodextrin-containing breast milk food
      substitutes].
AB  - Ten infant formulas containing maltodextrin were analysed for fermentable
      carbohydrates using enzymatic analysis test-combinations and a spectrophotometer.
      Besides lactose, sucrose and fructose an assessment was made of sugars typically
      contained in maltodextrin and corn syrup, namely maltose, maltotriose and
      glucose. Total carbohydrate was up to 10.3 g in 100 ml standard sample.
      Cariogenic sugars were found in concentrations between 4.0 and 7.3 g/100 ml.
      Declaration of the different types of carbohydrates, especially of
      maltodextrin/corn syrup proved to be insufficient in some products and
      consequently the consumer is not able to understand their cariogenic potential.

PMID- 7716463
TI  - [The cariostatic mechanisms of action of fluorides. A review].
AB  - In the past the inhibition of caries by fluorides was ascribed to the reduced
      solubility of enamel due to the incorporation of F- into the enamel mineral.
      During the last years the understanding of the cariostatic mechanism has changed
      fundamentally. Based on these new findings the loosely bound fluorides, which are
      present in the surroundings of the teeth after application of topicals, are
      regarded as decisive for the caries preventing effect by causing an inhibition of
      demineralization, enhancing the remineralization process and supporting the
      precipitation of CaF2. The formation of CaF2 is induced after application of
      topicals, and the material stays relatively stable in the mouth, due to adsorbed
      HPO4(2-) ions at the surface of CaF2. During the cariogenic challenge, CaF2
      releases F- ions due to the reduced concentration of HPO4(2-) ions at acidic pH
      values. The CaF2 therefore functions as a pH-controlled F(-)-reservoir and is the
      most important supplier of free F- ions during the cariogenic challenge.

PMID- 7716464
TI  - [Is adrenaline in a 2% lidocaine solution after enoral injection hemodynamically
      effective?].
AB  - Adrenaline in local anesthetic solutions is thought to be the causative factor of
      acute exacerbations of preexisting cardiac diseases during dental anesthesia.
      This assumption presupposes the systemic effectiveness of adrenaline when
      coinjected with a local anesthetic drug. To test the above assumption,
      cardiovascular effects (PS, PD, dP/dTmax LVEP, CO, HR, EGG) and arterial drug
      concentrations were measured before and after injection of 1.0 ml/kg b.w. of a
      0.9% NaCl, 1:300,000/1:100,000 adrenaline-HCl or 2% lidocaine-HCl alone and in
      combination into the mucobuccal fold of adrenalectomized rats. The transient
      increase in the cardiovascular parameters by adrenaline was abolished by
      lidocaine coinjection. The cardiodepressant effect of plain lidocaine was only
      reversed by the higher adrenaline dose, which however induced a small fall in PD,
      R and PM. Lidocaine increased the bioavailability of adrenaline from the
      intraoral depot. Inhibition of COMT activity by lidocaine may contribute to this
      effect. These findings demonstrate no cardiac response to adrenaline, up to
      1:100,000 in a 2% lidocaine solution. In agreement with clinical findings the
      1:100,000 adrenaline containing solution can be safely used in compromised
      cardiovascular patients. However, an interaction between a vasoactive
      comedication and lidocaine/adrenaline on the vascular system has to be taken into
      consideration.

PMID- 7716465
TI  - [Esthetics in periodontology].

PMID- 7716466
TI  - [Is oral prevention relevant to general medicine? The promotion of general health
      by improving oral health].

PMID- 7716467
TI  - [Prophylaxis personnel--the entrepreneurial aspects. A survey of 24 female dental
      hygienists in 16 private practices].

PMID- 7716468
TI  - [SDI: goal, concept, methods and means. Secours Dentaire International].

PMID- 7716469
TI  - [Caries prevention in Peru].

PMID- 7716470
TI  - [The latest development in bonding technic and dosage reduction in dental x-ray
      diagnosis. A report on the technical meeting of the SGK/SSODF of 10-11 November
      1994 in Basel. Schweizerische Gesellschaft fur Kieferorthopadie/Societe Suisse
      d'Orthopedie dento-faciale].

PMID- 7716471
TI  - [Surgical endodontics. A report on the video-supported practical operating course
      on surgical endodontics of 11 November 1994 in Zurich].

PMID- 7716472
TI  - [Individual prophylaxis in transition. A report on the 7th Innsbruck Dental
      Prophylaxis Congress of 21-22 October 1994].

PMID- 7716473
TI  - [A topical discussion on 4 papers on dental hygiene in Switzerland. Interview by
      Kurt Venner].

PMID- 7716474
TI  - [The dental hygienist--a discriminating profession].

PMID- 7716475
TI  - [The institutionalization of continuing education for dental hygienists].

PMID- 7716476
TI  - [Esthetics, dental materials, medical and legal risks in dentistry. A report on
      the 118th Annual Meeting of the German Society for Dentistry, Oral Medicine and
      Orthodontics with the Study Group for Forensic Dentistry in the Society from 6 to
      9 October 1994 in Travemunde (Germany)].

PMID- 7716477
TI  - [The bear didn't suffer and didn't have a bill to pay!].

PMID- 7716478
TI  - [The Emmental-Oberaargau Veterinary Society 1887-1943].

PMID- 7716479
TI  - [Veterinary evolution in Iron Age discoveries in Glozel (France)].

PMID- 7716480
TI  - [Max Kleiber--life and work].

PMID- 7716481
TI  - [The prevalence of paratuberculosis in the Plateau de Diesse region].
AB  - We analysed 595 cows in 20 herds for serological evidence of paratuberculosis
      with an ELISA procedure for which we had recently determined a sensitivity of 50%
      and a specificity of 98%, and we obtained an overall calculated real prevalence
      of 5.99%. In two herds with clinical cases of paratuberculosis, the calculated
      true prevalence of seroreactors was 21.47%. In 9 herds with clinical suspicion of
      Johne's disease, the rate was 4.23%, 9 herds without any clinical suspicion
      showed a mean prevalence of 0%. Whereas the trend was clear for groups of herds,
      the observed prevalence in individual herds varied from 0% to 17.9%, without
      obvious association with manifest clinical problems of paratuberculosis.

PMID- 7716482
TI  - [Military veterinary service and the formation of veterinary medicine and
      farriery in the 19th century].

PMID- 7716483
TI  - The price of prevention.

PMID- 7716484
TI  - The end of the road.

PMID- 7716485
TI  - I get no kick from CH3CH2OH.

PMID- 7716487
TI  - Changing the image.

PMID- 7716486
TI  - Genes in the not so public domain.

PMID- 7716488
TI  - Understanding the genetic construction of behavior.

PMID- 7716489
TI  - Proceedings of the International Conference on the Environmental and Health
      Aspects Related to the Production of Aluminium. Bergen, Norway, 28-30 June 1994.

PMID- 7716490
TI  - Aluminum exposure and excretion.
AB  - Occupational exposure to aluminum can be associated with increases in both
      urinary aluminum excretion and serum aluminum. In most studies, the increases in
      urinary aluminum are proportionately greater than the changes in serum aluminum.
      A similar pattern of response follows increases in dietary aluminum intake. Thus,
      there is ample evidence for systemic aluminum absorption from occupational
      exposure to airborne aluminum as well as dietary intake. Although both
      circumstances are accompanied by a similar renal response, there is little
      information explaining how normal kidneys augment renal excretion with only
      trivial changes in serum aluminum concentrations. In addition, it is not
      understood how airborne exposure to microgram amounts of aluminum produces
      significant increases in urinary aluminum. The latter observation suggests the
      presence of a sensitive uptake process for aluminum from airway exposure.

PMID- 7716491
TI  - Asthma and respiratory problems--a review.
AB  - Occupational asthma is the principal respiratory health problem within the
      primary aluminium industry. Current evidence indicates that it is irritant
      induced and due to occupational exposure to the inhalation of gaseous or
      particulate fluoride compounds. Following transfer from the occupational exposure
      of those who develop asthma, there is commonly symptomatic improvement. A
      programme of compulsory respiratory protection, progressive engineering
      improvements and of regular screening of potroom workers aimed at early
      detection, and the transfer of asthmatic workers from that environment has
      resulted not only in improvement of asthmatic symptoms among them, but also in
      the majority of an improvement in bronchial responsiveness as assessed by
      methacholine inhalation. The majority of studies indicate a slightly increased
      prevalence of symptoms of chronic bronchitis and of chronic obstructive pulmonary
      disease among workers in carbon bake areas, although tobacco smoking has a
      greater and additive effect. Only a trivial number of clinical cases of pulmonary
      fibrosis ascribed to aluminium compounds has been reported. Particle size limits
      smelter grade primary alumina reaching the alveoli of the lung.

PMID- 7716492
TI  - Use of bone mineral content determination by X-ray absorptiometry in the
      evaluation of osteodystrophy among workers exposed to aluminium powders.
AB  - Within the framework of a cross-sectional study, we investigated 61 employees in
      an aluminium powder factory to see if aluminium had an influence on bone mineral
      content using the non-invasive method of bone density measurement. Thirty-two
      workers had been employed for, on average, 151 months in the area of aluminium
      powder production. Twenty-nine employees in the same factory, who had not been
      engaged in the production of aluminium powder, served as controls. The groups
      differed significantly in the concentrations of aluminium in urine and plasma.
      The bone mineral content, which was determined in the lumbar spine by means of
      photon absorptiometry showed no significant difference between the groups. The
      bone density value amounted to 1.00 g/cm2 for those exposed and 1.02 g/cm2 for
      the control group (median values). No correlation could be determined between the
      values obtained from the biological monitoring of the plasma or the duration of
      exposure and the bone density values. To summarise, using osteodensitometry as
      the method of investigation here, no influence could be detected for an
      occupational exposure to aluminium powders on the mineral salt content of the
      skeletal system in the area of the lumbar spine.

PMID- 7716493
TI  - Biomonitoring of genotoxic exposure in aluminium plant workers by determination
      of DNA adducts in human peripheral blood lymphocytes.
AB  - A longitudinal human biomonitoring study has been performed in two Hungarian
      primary aluminium production plants that operated Soderberg cells. Carcinogen-DNA
      adducts have been determined by 32P-postlabelling and competitive enzyme-linked
      immunosorbent assay in peripheral blood lymphocytes from potroom workers and
      occupationally unexposed control individuals. Blood samples were collected on
      three occasions; the first two occasions were 1 year apart during normal
      operation, and the last samples were taken 6 months after close-down of aluminium
      production. Assays of the first set of samples demonstrated no significant
      difference between the control group and workers in Plant I. Workers in Plant II
      had significantly higher DNA adduct levels than individuals in the control group
      and workers in Plant I. One year later a significant elevation of DNA adducts was
      detected in Plant I so that values approached those seen in Plant II, which
      remained unchanged. In the last sample set there was no difference between former
      potroom workers and occupationally unexposed individuals. The results suggest
      that carcinogen-DNA adducts are a useful biomarker for monitoring occupational
      genotoxic exposure to polycyclic aromatic hydrocarbons, and that the findings can
      contribute to improved health risk assessment.

PMID- 7716494
TI  - First international workshop on hydroxypyrene as a biomarker for PAH exposure in
      man--summary and conclusions.

PMID- 7716495
TI  - Occupational PAH exposure: urinary 1-hydroxypyrene levels of coke oven workers,
      aluminium smelter pot-room workers, road pavers, and occupationally non-exposed
      persons in Sweden.
AB  - Polycyclic aromatic hydrocarbon (PAH) levels in air, and worker urinary 1
      hydroxypyrene levels were studied in a coke oven, a Soderberg aluminium smelter
      pot-room, and during road-paving. Increased PAH exposure was shown to cause
      increased 1-hydroxypyrene excretion. Road-paving gave low PAH exposure, but
      resulted in a detectable elevated urinary 1-hydroxypyrene level. Background
      urinary 1-hydroxypyrene levels in office workers were determined, and a
      statistically significant difference between smokers and non-smokers was
      observed. It is suggested that urinary 1-hydroxypyrene can be used as biological
      exposure index for PAH exposure.

PMID- 7716496
TI  - Urinary excretion kinetics of 1-hydroxypyrene in volunteers exposed to pyrene by
      the oral and dermal route.
AB  - Two well-informed human volunteers were exposed to 500 micrograms pyrene by
      ingestion and by dermal application, in two separate experiments. Urinary
      measurements of 1-hydroxypyrene (1-OHP) were performed on all micturitions taken
      at intervals of 0.5-4 h for a total period of 48 h after dosing. Following the
      absorption phase, 1-OHP is excreted with a first order apparent half-life of
      approximately 12 h for both volunteers and both exposure routes. These results
      compare well with other previously published studies. A more refined analysis of
      the data was performed using a two-compartment toxicokinetic model for 'pyrene'
      (its fraction eventually excreted as 1-OHP). As it was found that a classical
      first-order system did not adequately fit the data, a non-linear term was
      introduced in the model for the elimination of urinary 1-OHP. Computer iteration
      performed on the oral absorption data allowed an estimation of various
      toxicokinetic parameter values. The mean intercompartmental exchange (k12 and
      k21) and elimination coefficients were 0.010, 0.006 and 0.012 min-1,
      respectively. The first two values compare well with those previously published
      for the rat, whereas the latter is smaller in humans. These values were used to
      satisfactorily simulate the experimental data for both routes of exposure,
      adjusting only for kabs which was estimated at 0.014 and 0.0029 min-1 for the
      oral and dermal exposure, respectively. The proposed model generates new
      hypotheses on the metabolism of pyrene. The information collected will contribute
      to the validation of the utilisation of 1-OHP as a biological indicator of
      exposure to pyrene.

PMID- 7716497
TI  - Patterns of 1-hydroxypyrene excretion in volunteers exposed to pyrene by the
      dermal route.
AB  - The urinary excretion profiles following exposure to pyrene were established in
      one psoriasic patient under treatment with a coal tar-based shampoo and in two
      other volunteers exposed to a single dose of 100 microliters creosote and, in a
      separate experiment, to five consecutive daily dermal applications of 500
      micrograms pyrene on 200 cm2 of the inner face of the forearms. Timed
      micturitions were collected for up to 48 h following exposure. Both in the
      psoriasic patient and in the volunteers exposed to creosote, the excretion peaks
      between 10 and 15 h after application and first-order apparent half lives of 11.5
      15 h can be calculated for the elimination phase. Compatible with these
      observations, repeated exposure to pyrene in the volunteers causes an increase in
      peak and trough urinary 1-hydroxypyrene (1-OHP) values for the first few days
      following the first exposure. These results suggest that the difference between
      beginning-of-shift/beginning of work week and beginning-of-shift/end of work week
      1-OHP excretions should reflect the average exposure of the week in workers
      having a constant exposure to pyrene. The difference between the beginning- and
      end-of-shift excretion values of a given day should reflect the exposure of that
      day but the maximum excretion would be attained a few hours after termination of
      exposure.

PMID- 7716498
TI  - Background urinary 1-hydroxypyrene levels in non-occupationally exposed
      individuals in the Province of Quebec, Canada, and comparison with its excretion
      in workers exposed to PAH mixtures.
AB  - The urinary excretion of 1-hydroxypyrene (1-OHP) was measured in two reference
      groups of non-occupationally exposed individuals and in four groups of workers.
      Two of these groups were exposed to what were considered to be low levels of
      polycyclic aromatic hydrocarbons (PAH) on the basis that even post-shift 1-OHP
      excretion values were low (< 2 mumol/mol creatinine). Therefore, urine samples
      were collected from these workers after a period of > 60 h without occupational
      exposure which should yield values approaching background levels. Pooling these
      results with those of the reference groups yielded a total of 140 individuals
      having a mean (geometric) excretion of 0.08 mumol/mol creatinine and 5th, 50th
      and 95th percentiles of 0.02, 0.09 and 0.32 mumol/mol creatinine. The mean
      (geometric) excretion in the 95 nonsmokers and 45 smokers of this pool was 0.07
      and 0.12 mumol/mol creatinine, respectively (one-tailed Student t-test, P <
      0.001). Both this background excretion and the contribution of smoking appeared
      small in comparison with the excretion levels observed in some groups of exposed
      workers. Indeed, creosote workers described in this report had a geometric mean
      (range) excretion of 1.63 (0.18-10.47) mumol/mol creatinine during their working
      week. It is concluded that, for the biological monitoring of workers exposed to
      PAH, urinary 1-OHP appears to be a useful bioindicator for which background
      environmental contamination or smoking habits can be neglected in most cases.

PMID- 7716499
TI  - The elimination of 1-hydroxypyrene in the urine of the general population and
      workers with different occupational exposures to PAH.

PMID- 7716500
TI  - Urinary 1-hydroxypyrene as biomarker of exposure to polycyclic aromatic
      hydrocarbons in workers in petrochemical industries: baseline values and dermal
      uptake.
AB  - The suitability of urinary 1-hydroxypyrene as a biomarker for the assessment of
      exposure to polycyclic aromatic hydrocarbons (PAH) in petrochemical industries
      was evaluated in 562 workers involved in various operations in petrochemical
      industries. The median 1-hydroxypyrene concentration in 121 of these workers
      (both smokers and non-smokers) who had had no recent occupational exposure to PAH
      was 0.11 mumol/mol creatinine. The upper limit of the 95% confidence interval was
      0.51 mumol/mol creatinine. During activities with a low potential exposure to
      PAH, such as loading bitumen and the handling of clarified slurry oils and
      furfural extracts, 1-hydroxypyrene concentrations were only marginally increased
      compared with the values measured in the 121 workers with no recent occupational
      exposure to PAH. Despite the substantially higher potential exposure to PAH
      during clean-out operations of various oil refinery installations, the
      concentrations of 1-hydroxypyrene in the workers involved were in the same range.
      This suggests that personal protection equipment was generally adequate to
      prevent excessive exposure. However, in workers digging PAH-contaminated soil and
      workers engaged in the production of needle coke from ethylene cracker residue,
      significantly increased urinary 1-hydroxypyrene concentrations were measured. A
      major decrease in urinary 1-hydroxypyrene following the application of dermal
      protective equipment in the ground workers suggested that skin absorption plays a
      major role in occupational exposure to PAH. The excretion of 1-hydroxypyrene by
      the workers of the needle coke plant was investigated in relation to potential
      determinants of exposure to PAH. It was indeed found that not only inhalatory but
      also dermal exposure was a significant determinant of occupational exposure to
      PAH.

PMID- 7716502
TI  - Signals and communication.

PMID- 7716501
TI  - Estimation of reference values for urinary 1-hydroxypyrene and alpha-naphthol in
      Danish workers.
AB  - In order to assess environmentally and occupationally related exposures to PAH
      compounds it is essential to have reference or normal values in human body
      fluids. The establishment of reliable reference intervals is an absolute pre
      requisite in determining relationships between internal PAH exposure in humans
      and health effects in occupationally exposed workers. In this context the
      estimation of the biological level of PAH metabolites in urine from reference
      populations has become increasingly important in the field of environmental and
      occupational toxicology. The present study describes the calculation of tentative
      reference values for urinary 1-hydroxypyrene on the basis of two reference
      populations and for urinary alpha-naphthol on the basis of one reference
      population in accordance with IFCC recommendations. The study subjects were 115
      healthy male workers occupationally exposed to PAH at low levels and 121
      reference subjects non-occupationally exposed to PAH. Tentative reference values
      for urinary 1-hydroxypyrene were estimated. In addition, 236 healthy male workers
      were used to estimate tentative reference values for urinary alpha-naphthol. The
      reference populations were described by distribution free one-sided tolerance
      intervals. The 95% one-sided tolerance limit calculated for 1-hydroxypyrene in
      urine was 0.053 mumol/mol creatinine for non-occupationally exposed individuals
      and 0.169 mumol/mol creatinine for low level PAH exposed workers, with the
      coverage interval (95 +/- 4.5) percent at a probability of 0.95. Thus, the
      probability was 0.975 that the tolerance interval included at least 90.5% of the
      distribution. In addition, the probability was 0.025 that the tolerance interval
      included > 99.5% of the population. The tolerance interval for alpha-naphthol in
      urine was 5.665 mumol/mol creatinine with the coverage interval (95 +/- 4.5)
      percent at a probability of 0.95.

PMID- 7716503
TI  - Chimpanzee kinship.

PMID- 7716504
TI  - The theory of DNA bending.

PMID- 7716505
TI  - Biotech patents and "usefulness".

PMID- 7716506
TI  - Low-barrier hydrogen bonds.

PMID- 7716507
TI  - A movable institute: the AIDS dream team.

PMID- 7716508
TI  - Congressman uncovers the HIV conspiracy.

PMID- 7716509
TI  - Found: ash from the first stars?

PMID- 7716510
TI  - Trypanosome mystery solved?

PMID- 7716511
TI  - AIDS research. Cytokines move from the margins into the spotlight.

PMID- 7716512
TI  - Protein lipidation in cell signaling.
AB  - The ability of cells to communicate with and respond to their external
      environment is critical for their continued existence. A universal feature of
      this communication is that the external signal must in some way penetrate the
      lipid bilayer surrounding the cell. In most cases of such signal acquisition, the
      signaling entity itself does not directly enter the cell but rather transmits its
      information to specific proteins present on the surface of the cell membrane.
      These proteins then communicate with additional proteins associated with the
      intracellular face of the membrane. Membrane localization and function of many of
      these proteins are dependent on their covalent modification by specific lipids,
      and it is the processes involved that form the focus of this article.

PMID- 7716513
TI  - Notch signaling.
AB  - The Notch/Lin-12/Glp-1 receptor family mediates the specification of numerous
      cell fates during development in Drosophila and Caenorhabditis elegans. Studies
      on the expression, mutant phenotypes, and developmental consequences of
      unregulated receptor activation have implicated these proteins in a general
      mechanism of local cell signaling, which includes interactions between equivalent
      cells and between different cell types. Genetic approaches in flies and worms
      have identified putative components of the signaling cascade, including a
      conserved family of extracellular ligands and two cellular factors that may
      associate with the Notch Intracellular domain. One factor, the Drosophila
      Suppressor of Hairless protein, is a DNA-binding protein, which suggests that
      Notch signaling may involve relatively direct signal transmission from the cell
      surface to the nucleus. Several vertebrate Notch receptors have also been
      discovered recently and play important roles in normal development and
      tumorigenesis.

PMID- 7716514
TI  - Integrins and signal transduction pathways: the road taken.
AB  - Adhesive interactions play critical roles in directing the migration,
      proliferation, and differentiation of cells; aberrations in such interactions can
      lead to pathological disorders. These adhesive interactions, mediated by cell
      surface receptors that bind to ligands on adjacent cells or in the extracellular
      matrix, also regulate intracellular signal transduction pathways that control
      adhesion-induced changes in cell physiology. Though the extracellular molecular
      interactions involving many adhesion receptors have been well characterized, the
      adhesion-dependent intracellular signaling events that regulate these
      physiological alterations have only begun to be elucidated. This article will
      focus on recent advances in our understanding of intracellular signal
      transduction pathways regulated by the integrin family of adhesion receptors.

PMID- 7716515
TI  - Calcium signaling in neurons: molecular mechanisms and cellular consequences.
AB  - Neuronal activity can lead to marked increases in the concentration of cytosolic
      calcium, which then functions as a second messenger that mediates a wide range of
      cellular responses. Calcium binds to calmodulin and stimulates the activity of a
      variety of enzymes, including calcium-calmodulin kinases and calcium-sensitive
      adenylate cyclases. These enzymes transduce the calcium signal and effect short
      term biological responses, such as the modification of synaptic proteins and long
      lasting neuronal responses that require changes in gene expression. Recent
      studies of calcium signal-transduction mechanisms have revealed that, depending
      on the route of entry into a neuron, calcium differentially affects processes
      that are central to the development and plasticity of the nervous system,
      including activity-dependent cell survival, modulation of synaptic strength, and
      calcium-mediated cell death.

PMID- 7716516
TI  - Localization of protein kinases by anchoring proteins: a theme in signal
      transduction.
AB  - A fundamental question in signal transduction is how stimulation of a specific
      protein kinase leads to phosphorylation of particular protein substrates
      throughout the cell. Recent studies indicate that specific anchoring proteins
      located at various sites in the cell compartmentalize the kinases to their sites
      of action. Inhibitors of the interactions between kinases and their anchoring
      proteins inhibit the functions mediated by the kinases. These data indicate that
      the location of these anchoring proteins provides some of the specificity of the
      responses mediated by each kinase and suggest that inhibitors of the interaction
      between the kinases and their anchoring proteins may be useful as therapeutic
      agents.

PMID- 7716517
TI  - Cytokine signaling through nonreceptor protein tyrosine kinases.
AB  - Cytokines are a family of soluble mediators of cell-to-cell communication that
      includes interleukins, interferons, and colony-stimulating factors. The
      characteristic features of cytokines lie in their functional redundancy and
      pleiotropy. Most of the cytokine receptors that constitute distinct superfamilies
      do not possess intrinsic protein tyrosine kinase (PTK) domains, yet receptor
      stimulation usually invokes rapid tyrosine phosphorylation of intracellular
      proteins, including the receptors themselves. It is now clear that these
      receptors are capable of recruiting or activating (or both) a variety of
      nonreceptor PTKs to induce downstream signaling pathways. Thus, the
      intracytoplasmic structure of cytokine receptors has evolved so as to allow the
      combined action of different PTK family members expressed in different cell
      types, which may ultimately determine the activity of cytokines.

PMID- 7716518
TI  - Tyrosine phosphatases and the antibody response.

PMID- 7716519
TI  - Green fluorescent pets.

PMID- 7716520
TI  - Killing of trypanosomes by the human haptoglobin-related protein.
AB  - African trypanosomes cause disease in humans and animals. Trypanosoma brucei
      brucei affects cattle but not humans because of its sensitivity to a subclass of
      human high density lipoproteins (HDLs) called trypanosome lytic factor (TLF). TLF
      contains two apolipoproteins that are sufficient to cause lysis of T. b. brucei
      in vitro. These proteins were identified as the human haptoglobin-related protein
      and paraoxonase-arylesterase. An antibody to haptoglobin inhibited TLF activity.
      TLF was shown to exhibit peroxidase activity and to be inhibited by catalase.
      These results suggest that TLF kills trypanosomes by oxidative damage initiated
      by its peroxidase activity.

PMID- 7716521
TI  - Identification of a dual specificity kinase that activates the Jun kinases and
      p38-Mpk2.
AB  - One Ras-dependent protein kinase cascade leading from growth factor receptors to
      the ERK (extracellular signal-regulated kinases) subgroup of mitogen-activated
      protein kinases (MAPKs) is dependent on the protein kinase Raf-1, which activates
      the MEK (MAPK or ERK kinase) dual specificity kinases. A second protein kinase
      cascade leading to activation of the Jun kinases (JNKs) is dependent on MEKK (MEK
      kinase). A dual-specificity kinase that activates JNK, named JNKK, was identified
      that functions between MEKK and JNK. JNKK activated the JNKs but did not activate
      the ERKs and was unresponsive to Raf-1 in transfected HeLa cells. JNKK also
      activated another MAPK, p38 (Mpk2; the mammalian homolog of HOG1 from yeast),
      whose activity is regulated similarly to that of the JNKs.

PMID- 7716522
TI  - Crystal structure of the mammalian Grb2 adaptor.
AB  - The mammalian growth factor receptor-binding protein Grb2 is an adaptor that
      mediates activation of guanine nucleotide exchange on Ras. Grb2 binds to the
      receptor through its SH2 domain and to the carboxyl-terminal domain of Son of
      sevenless through its two SH3 domains. It is thus a key element in the signal
      transduction pathway. The crystal structure of Grb2 was determined to 3.1
      angstrom resolution. The asymmetric unit is composed of an embedded dimer. The
      interlaced junctions between the SH2 and SH3 domains bring the two adjacent faces
      of the SH3 domains in van der Waals contact but leave room for the binding of
      proline-rich peptides.

PMID- 7716523
TI  - Recruitment and activation of PTP1C in negative regulation of antigen receptor
      signaling by Fc gamma RIIB1.
AB  - Coligation of the Fc receptor on B cells, Fc gamma RIIB1, with the B cell antigen
      receptor (BCR) leads to abortive BCR signaling. Here it was shown that the Fc
      gamma RIIB1 recruits the phosphotyrosine phosphatase PTP1C after BCR coligation.
      This association is mediated by the binding of a 13-amino acid tyrosine
      phosphorylated sequence to the carboxyl-terminal Src homology 2 domain of PTP1C
      and activates PTP1C. Inhibitory signaling and PTP1C recruitment are dependent on
      the presence of the tyrosine within the 13-amino acid sequence. Inhibitory
      signaling mediated by Fc gamma RIIB1 is deficient in motheaten mice which do not
      express functional PTP1C. Thus, PTP1C is an effector of BCR-Fc gamma RIIB1
      negative signal cooperativity.

PMID- 7716524
TI  - Activity-dependent action potential invasion and calcium influx into hippocampal
      CA1 dendrites.
AB  - The temporal and spatial profile of activity-evoked changes in membrane potential
      and intracellular calcium concentration in the dendrites of hippocampal CA1
      pyramidal neurons was examined with simultaneous somatic and dendritic patch
      pipette recording and calcium imaging experiments. Action potentials are
      initiated close to the soma of these neurons and backpropagate into the dendrites
      in an activity-dependent manner; those occurring early in a train propagate
      actively, whereas those occurring later fail to actively invade the distal
      dendrites. Consistent with this finding, dendritic calcium transients evoked by
      single action potentials do not significantly attenuate with distance from the
      soma, whereas those evoked by trains attenuate substantially. Failure of action
      potential propagation into the distal dendrites often occurs at branch points.
      Consequently, neighboring regions of the dendritic tree can experience different
      voltage and calcium signals during repetitive action potential firing. The
      influence of backpropagating action potentials on synaptic integration and
      plasticity will therefore depend on both the extent of dendritic branching and
      the pattern of neuronal activity.

PMID- 7716525
TI  - Synaptic activation of voltage-gated channels in the dendrites of hippocampal
      pyramidal neurons.
AB  - Activation of dendritic voltage-gated ion channels by local synaptic input was
      tested by simultaneous dendrite-attached patch-clamp recordings and whole-cell
      somatic voltage recordings made from CA1 pyramidal neurons in hippocampal slices.
      Schaffer collateral stimulation elicited subthreshold excitatory postsynaptic
      potentials (EPSPs) that opened voltage-gated sodium and calcium channels in the
      apical dendrites. The EPSP-activated sodium channels opened near the peak of the
      EPSP, whereas low voltage-activated calcium channels opened near the EPSP peak
      and during the decay phase. Dendritic high voltage-activated channels required
      somatic action potential generation or suprathreshold synaptic trains for
      activation. Dendritic voltage-gated channels are, therefore, likely to
      participate in dendritic integration of synaptic events.

PMID- 7716526
TI  - Silver as a probe of pore-forming residues in a potassium channel.
AB  - In voltage-dependent potassium channels, the molecular determinants of ion
      selectivity are found in the P (pore) region, a stretch of 21 contiguous
      residues. Cysteine was introduced at each P region position in a Shaker potassium
      channel. Residues projecting side chains into the pore were identified by means
      of channel inhibition by a sulfhydryl-reactive potassium ion analog, silver ion.
      The pattern of silver ion reactivity contradicts a beta barrel architecture of
      potassium channel pores.

PMID- 7716528
TI  - The Pharmacia Biotech & Science Prize.

PMID- 7716527
TI  - Revealing the architecture of a K+ channel pore through mutant cycles with a
      peptide inhibitor.
AB  - Thermodynamic mutant cycles provide a formalism for studying energetic coupling
      between amino acids on the interaction surface in a protein-protein complex. This
      approach was applied to the Shaker potassium channel and to a high-affinity
      peptide inhibitor (scorpion toxin) that binds to its pore entryway. The
      assignment of pairwise interactions defined the spatial arrangement of channel
      amino acids with respect to the known inhibitor structure. A strong constraint
      was placed on the Shaker channel pore-forming region by requiring its amino
      terminal border to be 12 to 15 angstroms from the central axis. This method is
      directly applicable to sodium, calcium, and other ion channels where inhibitor or
      modulatory proteins bind with high affinity.

PMID- 7716529
TI  - Guidelines for xenotransplantation.

PMID- 7716530
TI  - AIDS data.

PMID- 7716531
TI  - "More" is not "different".

PMID- 7716532
TI  - Cell cycle arrest.

PMID- 7716533
TI  - A molecular approach to cancer risk.

PMID- 7716534
TI  - Germans buy Nature's publisher.

PMID- 7716535
TI  - Antibodies linked to rare epilepsy.

PMID- 7716536
TI  - Anthropologists overturn old ideas about new developments.

PMID- 7716537
TI  - Researchers find molecules that muzzle killer cells.

PMID- 7716538
TI  - AIDS therapy. New hope against blindness.

PMID- 7716539
TI  - Pas de deux or more: the sulfonylurea receptor and K+ channels.

PMID- 7716540
TI  - Adaptive mutation: who's really in the garden?

PMID- 7716541
TI  - Mercury-199 NMR of the metal receptor site in MerR and its protein-DNA complex.
AB  - Structural insights have been provided by mercury-199 nuclear magnetic resonance
      (NMR) into the metal receptor site of the MerR metalloregulatory protein alone
      and in a complex with the regulatory target, DNA. The one- and two-dimensional
      NMR data are consistent with a trigonal planar Hg-thiolate coordination
      environment consisting only of Cys side chains and resolve structural aspects of
      both metal ion recognition and the allosteric mechanism. These studies establish
      199Hg NMR techniques as useful probes of the metal coordination environment of
      regulatory proteins, copper enzymes, and zinc transcription factor complexes as
      large as 50 kilodaltons.

PMID- 7716542
TI  - Superantigen-dependent, cell-mediated cytotoxicity inhibited by MHC class I
      receptors on T lymphocytes.
AB  - Bacterial superantigens bind with high affinity to major histocompatibility
      complex (MHC) class II antigens on antigen-presenting cells and with T cell
      antigen receptor (TCR) beta chains on T lymphocytes, which results in the T cell
      activation responsible for toxic shock syndrome and food poisoning. Many
      cytotoxic T lymphocyte (CTL) clones were shown to have receptors for human
      leukocyte antigen (HLA) class I molecules that inhibited superantigen-induced
      cytotoxicity against appropriate class I-bearing target cells. One type of
      inhibitory receptor, NKB1, was present on CD4+ and CD8+TCR alpha beta+ CTL clones
      and blocked the killing of staphylococcal enterotoxin B (SEB)-coated targets
      bearing certain polymorphic HLA-B molecules. Expression of HLA-A, -B, and -C
      molecules on the SEB-coated targets also protected against cytolysis mediated by
      many NKB1-negative T cell clones, suggesting the presence of additional
      inhibitory MHC class I receptors. These HLA class I receptors may limit tissue
      destruction and possibly autoimmunity caused by activated T lymphocytes.

PMID- 7716543
TI  - Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B
      recognition by human natural killer cells.
AB  - Cytotoxicity by natural killer (NK) cells is inhibited by major
      histocompatibility complex (MHC) class I molecules on target cells. This
      inhibition may be mediated by NK receptors with different MHC specificities. A
      family of four NK-specific complementary DNAs (cDNAs), designated NKATs (NK
      associated transcripts), was identified that encoded related transmembrane
      proteins, characterized by an extracellular region with two or three
      immunoglobulin-superfamily domains and by a cytoplasmic domain with an unusual
      antigen receptor activation motif (ARAM). The distribution of these cDNAs was
      clonotypic and correlated with NK cell inhibition by particular class I alleles.
      Thus, NKAT cDNAs may encode receptors for class I molecules on NK cells.

PMID- 7716544
TI  - The role of Ig beta in precursor B cell transition and allelic exclusion.
AB  - Lymphocytes express multicomponent receptor complexes that mediate diverse
      antigen-dependent and antigen-independent responses. Despite the central role of
      antigen-independent events in B cell development, little is known about the
      mechanisms by which they are initiated. The association between the membrane
      immunoglobulin (Ig) M heavy chair (micron) and the Ig alpha-Ig beta heterodimer
      is now shown to be essential in inducing both the transition from progenitor to
      precursor B cells and subsequent allelic exclusion in transgenic mice. The
      cytoplasmic domain of Ig beta is sufficient to induce these early antigen
      independent events by a mechanism that requires conserved tyrosine residues in
      this protein.

PMID- 7716545
TI  - Adaptive mutation in Escherichia coli: a role for conjugation.
AB  - When subjected to selective conditions that impose starvation, a bacterial
      population can accumulate mutations, called adaptive, that allow colony
      formation. Here, the reversion of a lac allele under selective conditions, in a
      model system using Escherichia coli with the lac mutation on an F' plasmid, was
      shown to require the conjugational capacity of the plasmid. Reversion associated
      with transfer was shown, and when the same lac allele was chromosomal, reversion
      to Lac+ was 25 to 50 times less frequent. Postplating reversion was 25 times less
      when mating was inhibited by the presence of detergent. Mutability associated
      with conjugation provides new ways of thinking about the origin of adaptive
      mutations.

PMID- 7716546
TI  - Evidence that F plasmid transfer replication underlies apparent adaptive
      mutation.
AB  - An Escherichia coli K12 strain, FC40, has been used extensively in the analysis
      of adaptive mutability. This strain carries a revertible mutant lac allele on an
      F plasmid and accumulates Lac+ (lactose utilizing) revertants, but not unselected
      mutants, when placed on selective medium. These adaptive mutations are a subset
      of spontaneous types and their formation depends on the RecABC functions. Data
      presented here suggest that this phenomenon depends on transfer functions of the
      F factor. Fertility inhibition eliminates RecA-dependent adaptive reversion.
      Thus, "adaptive" revertants may form during replication from the transfer origin,
      whereas loci in the nonreplicating chromosome show little mutation.

PMID- 7716547
TI  - Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of
      insulin secretion.
AB  - Sulfonylureas are a class of drugs widely used to promote insulin secretion in
      the treatment of non-insulin-dependent diabetes mellitus. These drugs interact
      with the sulfonylurea receptor of pancreatic beta cells and inhibit the
      conductance of adenosine triphosphate (ATP)-dependent potassium (KATP) channels.
      Cloning of complementary DNAs for the high-affinity sulfonylurea receptor
      indicates that it is a member of the ATP-binding cassette or traffic ATPase
      superfamily with multiple membrane-spanning domains and two nucleotide binding
      folds. The results suggest that the sulfonylurea receptor may sense changes in
      ATP and ADP concentration, affect KATP channel activity, and thereby modulate
      insulin release.

PMID- 7716548
TI  - Mutations in the sulfonylurea receptor gene in familial persistent
      hyperinsulinemic hypoglycemia of infancy.
AB  - Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal
      recessive disorder characterized by unregulated insulin secretion, is linked to
      chromosome 11p14-15.1. The newly cloned high-affinity sulfonylurea receptor (SUR)
      gene, a regulator of insulin secretion, was mapped to 11p15.1 by means of
      fluorescence in situ hybridization. Two separate SUR gene splice site mutations,
      which segregated with disease phenotype, were identified in affected individuals
      from nine different families. Both mutations resulted in aberrant processing of
      the RNA sequence and disruption of the putative second nucleotide binding domain
      of the SUR protein. Abnormal insulin secretion in PHHI appears to be caused by
      mutations in the SUR gene.

PMID- 7716549
TI  - Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein.
AB  - Infection by human immunodeficiency virus-type 1 (HIV-1) is typified by the
      progressive depletion of CD4 T lymphocytes and deterioration of immune function
      in most patients. A central unresolved issue in acquired immunodeficiency
      syndrome (AIDS) pathogenesis is the mechanism underlying this T cell depletion.
      HIV-1 Tat protein was shown to induce cell death by apoptosis in a T cell line
      and in cultured peripheral blood mononuclear cells from uninfected donors. This
      Tat-induced apoptosis was inhibitable by growth factors and was associated with
      enhanced activation of cyclin-dependent kinases.

PMID- 7716550
TI  - Measurement of interhelical electrostatic interactions in the GCN4 leucine
      zipper.
AB  - The dimerization specificity of the bZIP transcription factors resides in the
      leucine zipper region. It is commonly assumed that electrostatic interactions
      between oppositely charged amino acid residues on different helices of the
      leucine zipper contribute favorably to dimerization specificity. Crystal
      structures of the GCN4 leucine zipper contain interhelical salt bridges between
      Glu20 and Lys15' and between Glu22 and Lys27'. 13C-nuclear magnetic resonance
      measurements of the glutamic acid pKa values at physiological ionic strength
      indicate that the salt bridge involving Glu22 does not contribute to stability
      and that the salt bridge involving Glu20 is unfavorable, relative to the
      corresponding situation with a neutral (protonated) Glu residue. Moreover, the
      substitution of Glu20 by glutamine is stabilizing. Thus, salt bridges will not
      necessarily contribute favorably to bZIP dimerization specificity and may indeed
      be unfavorable, relative to alternative neutral-charge interactions.

PMID- 7716551
TI  - Nicotinic receptor binding site probed with unnatural amino acid incorporation in
      intact cells.
AB  - The nonsense codon suppression method for unnatural amino acid incorporation has
      been applied to intact cells and combined with electrophysiological analysis to
      probe structure-function relations in the nicotinic acetylcholine receptor.
      Functional receptors were expressed in Xenopus oocytes when tyrosine and
      phenylalanine derivatives were incorporated at positions 93, 190, and 198 in the
      binding site of the alpha subunit. Subtle changes in the structure of an
      individual side chain produced readily detectable changes in the function of this
      large channel protein. At each position, distinct features of side chain
      structure dominated the dose-response relation, probably by governing the agonist
      receptor binding.

PMID- 7716552
TI  - Patterns of human growth.

PMID- 7716553
TI  - Variability among human umbilical vein endothelial cultures.

PMID- 7716554
TI  - Myocardial perfusion imaging for evaluating interventions in coronary artery
      disease.
AB  - Myocardial perfusion imaging provides a means for evaluating the effects of
      interventional therapy in several groups of patients with coronary artery
      disease. In patients with unstable angina, imaging during or after chest pain can
      be used to identify areas of jeopardized myocardium and to predict the risk of
      subsequent cardiac events including myocardial infarction. In patients with acute
      myocardial infarction, the effect of thrombolytic therapy can be monitored, and
      in patients with chronic ischemia and left ventricular dysfunction, thallium
      imaging can be used to predict whether revascularization will improve myocardial
      function. In patients with stable coronary artery disease, perfusion imaging has
      been used to evaluate efficacy of anti-anginal medications. This article reviews
      the use of myocardial perfusion imaging in determining the need for, and success
      of, various medical and surgical therapeutic interventions in patients with
      ischemic heart disease.

PMID- 7716555
TI  - Hepatobiliary scintigraphy after biliary tract surgery.
AB  - Hepatobiliary scintigraphy provides a rapid, noninvasive, accurate means of
      assessing patients after biliary tract surgery. This is especially important,
      given the high incidence of biliary and enteric diseases. In this review article,
      the role of radionuclide imaging in postcholecystectomy and postgastroenteric
      surgery patients will be examined, as well as following invasive procedures and
      trauma.

PMID- 7716556
TI  - Radionuclide imaging after skeletal interventional procedures.
AB  - Although nuclear medicine is often used as an adjunct to planning skeletal
      therapeutic interventions, its role in the assessment of these various
      interventional procedures, after the fact, is equally important. Skeletal
      therapeutic interventions studied with radionuclide imaging include bone grafts,
      the postoperative spine, and joint replacements. Vascularized bone grafts allow
      the successful reconstruction of large bone gaps. Early detection of vascular
      compromise permits prompt reevaluation of the vascular anastomosis so that
      potentially reversible causes of ischemia can be corrected. Radionuclide bone
      scintigraphy is a simple noninvasive method to evaluate the anastomotic patency
      of these grafts. Scintigraphically, vascular patency is characterized by normal
      or diffusely increased tracer uptake throughout the graft, whereas failure of the
      graft presents as photopenia. Bone scintigraphy, especially single photon
      emission computed tomography (SPECT), is of considerable value in the work-up of
      patients with persistent back pain after spinal surgery. Postoperatively, spinal
      fusion is characterized by diffusely increased uptake of radiotracer in the fused
      area. In contrast, focally increased uptake has been shown to be related to bony
      nonunion or pseudoarthroses. In patients who have undergone laminectomy, SPECT
      bone scintigraphy can localize the level of maximum instability and vertebral
      stress. The radionuclide evaluation of joint replacement complications,
      especially of hip and knee prostheses, has been extensively studied for nearly 2
      decades. Bone scintigraphy is probably most useful when the images are normal.
      Although periprosthetic sites of increased uptake may be indicative of
      postoperative problems such as loosening or infection, they may also merely
      reflect postoperative changes. Dual tracer studies, focusing primarily on the
      diagnosis of the infected joint replacement, have consequently become the norm.
      Bone-gallium scintigraphy was the earliest dual tracer modality used, with an
      accuracy of 60% to 80%. The current radionuclide study of choice for diagnosing
      the infected prosthesis is labeled leukocyte-marrow imaging. Both leukocytes and
      colloid tracers accumulate in marrow, whereas only leukocytes accumulate in
      infection. This technique facilitates the discrimination of labeled leukocyte
      uptake in aberrant, but not abnormal, marrow from uptake in infection. The
      reported accuracy of this technique consistently exceeds 90%.

PMID- 7716557
TI  - Role of nuclear medicine in liver transplantation.
AB  - Orthotopic liver transplantation is now a very well-established technique for
      treating patients with end-stage liver disease. Since 1967, more than 26,000
      liver transplants have been performed, including 15,000 in the United States. The
      overall 1-year survival rate is approximately 80% and 5-year survival is 70%.
      Nuclear imaging plays an important role in the management of liver transplant
      recipients before and after liver transplantation. The evaluation of candidates
      potentially includes liver-spleen scan for liver volume, multiple gated
      acquisition scan, adenosine or stress thallium study, bone scan, and quantitative
      ventilation perfusion scan for hepatopulmonary syndrome. In the post-transplant
      phase, the deconvolution analysis (which corrects for the problem of
      recirculation) is a promising tool for diagnosing rejection, although its role in
      the transplant population has to be established. A variety of nuclear medicine
      techniques are helpful in the postoperative diagnosis of biliary complications.
      By performing a semiquantitative analysis to discriminate hepatocyte dysfunction
      from biliary disease and measuring hepatocyte extraction fraction by
      deconvolution analysis and excretion, (T1/2 values measured by the nonlinear list
      squares technique) have been very promising.

PMID- 7716558
TI  - Radionuclide evaluation of renal transplants.
AB  - Chronic renal failure caused by hypertension or by parenchymal kidney disease is
      a very common global health problem. Patients with chronic renal failure have two
      therapeutic options, dialysis and transplantation, of which transplantation has
      become a preferred modality. This review article is an update of a more
      comprehensive previous review (Semin Nucl Med, 181-198, 1988) and concentrates on
      the changes that have taken place in this field in recent years. These changes
      comprise new criteria for the selection of transplant candidates, newer
      techniques for the diagnosis of medical and surgical complications after
      transplantation, the use of new tracers (Tc-99m MAG3), and new antirejection
      regimens.

PMID- 7716559
TI  - The role of Ga-67 scintigraphy in evaluating the results of therapy of lymphoma
      patients.
AB  - Gallium-67 scintigraphy using high-dose, modern equipment, and SPECT plays an
      important role in the evaluation of patients with lymphoma after treatment. Being
      a viability agent, taken up by lymphomatous, but not by necrotic or fibrotic
      tissue, it is used to assess the nature of a residual mass after treatment.
      Gallium also predicts disease-free survival and overall survival after treatment.
      It is used with high sensitivity and specificity for diagnosis of recurrence
      after a continuous clinical remission, which is achieved after successful
      treatment. A potential use for Gallium is in early evaluation, during treatment,
      of the rapidity of response. This evaluation determines early the effectiveness
      of therapy in the individual patient. After treatment Ga-67 scintigraphy appears
      to be superior to computed tomography and probably magnetic resonance imaging. It
      is used routinely in the management of patients with lymphoma.

PMID- 7716560
TI  - Unilateral absence or near absence of pulmonary perfusion on lung scanning.

PMID- 7716561
TI  - [The Vaugirard Hospital. Accredited by WHO for promotion of public health].

PMID- 7716562
TI  - [The Rainbow Space. A gerontologic day care hospital].

PMID- 7716563
TI  - [The role of the social service. Using the hospitalization to mobilize a new
      dynamic at home].

PMID- 7716564
TI  - [Home visit before discharge of the aged patient].

PMID- 7716565
TI  - [Family participation].

PMID- 7716566
TI  - [Meetings between nursing personnel and families].

PMID- 7716567
TI  - [Forming a partnership between hospital and volunteers].

PMID- 7716569
TI  - [For nursing ethics].

PMID- 7716568
TI  - [Public conferences. Exchanges and information about old age].

PMID- 7716570
TI  - [Prevention of falls in hospitalized patients].

PMID- 7716571
TI  - [A new hospital opened for the town].

PMID- 7716572
TI  - [Quality of nursing care].

PMID- 7716573
TI  - [Drugs for Alzheimer's disease].

PMID- 7716574
TI  - [The town-hospital network].

PMID- 7716575
TI  - [Healing of chronic wounds. Use of dressings].

PMID- 7716576
TI  - [Formation of a bedsore].

PMID- 7716577
TI  - [The stages of healing of decubitus ulcers].

PMID- 7716578
TI  - [The process of prevention of decubitus ulcers].

PMID- 7716580
TI  - [Pain in patients with decubitus ulcers].

PMID- 7716579
TI  - [Prevention and treatment of decubitus ulcers].

PMID- 7716581
TI  - [History of a project. Option "Zero Bedsores"].

PMID- 7716582
TI  - [The ethical decision; a complex decision].

PMID- 7716584
TI  - [Talking about the body ... that fabulous machine].

PMID- 7716583
TI  - [Follow-up of the nursing diagnosis: fatigue].

PMID- 7716585
TI  - [An insidious malaise].

PMID- 7716587
TI  - [Sumatriptan].

PMID- 7716586
TI  - [The healing of wounds. Biology and physiopathology].

PMID- 7716588
TI  - Hyperlipidemia: perspectives in diagnosis and treatment.
AB  - Several forms of dyslipidemia are associated with premature coronary artery
      disease (CAD) and other vascular disease. These include elevated low-density
      lipoprotein cholesterol, low levels of high-density lipoprotein cholesterol, and
      elevated triglyceride. Because of the high incidence of CAD in many Western
      countries, including the United States, guidelines for managing dyslipidemia and
      reducing the risk of CAD have been promulgated. The National Cholesterol
      Education Program (NCEP) of the National Institutes of Health recently released
      revised guidelines for the treatment of adults with dyslipidemia, as did the
      European Atherosclerosis Society. Although the two reports differ in emphasis,
      both recommend routine screening of adults to identify specific individuals at
      high risk for future CAD events.

PMID- 7716589
TI  - The American Social Health Association celebrates 80 years of fighting sexually
      transmitted diseases.
AB  - The American Social Health Association (ASHA) can look back on 80 years of
      service as the only national nongovernmental organization devoted exclusively to
      prevention of sexually transmitted diseases (STDs). The valuable contributions
      made by physicians since the agency's founding in 1914 are noted and gratefully
      acknowledged. To commemorate its 80th anniversary, ASHA recently published a
      history that discusses the movements leading to ASHA's founding, the
      organization's work with the military during the World Wars, the changing face of
      STD control once penicillin became widely available in the 1940s, and the
      response to newly identified infections in recent decades. It also lists ASHA's
      founders, board presidents, executive directors, and recipients of the William
      Freeman Snow Award for outstanding contributions in the field of sexually
      transmitted diseases. The history was written by Kay Flaminio and David Klaassen
      of the ASHA Archive. This article summarizing ASHA's history was written
      especially for the Journal by Sam A. Nixon and Kay Flaminio. Nixon, a long-time
      member of the Southern Medical Association, recently retired as an associate
      network medical director of BlueCross BlueShield of Texas. He has maintained an
      interest in STD prevention and the work of the ASHA for many years, currently
      serving as the vice chair of ASHA's board of directors. Kay Flaminio is a member
      of the staff of ASHA.

PMID- 7716590
TI  - Meropenem versus imipenem/cilastatin in the treatment of hospitalized patients
      with skin and soft tissue infections.
AB  - Meropenem is a new carbapenem antibiotic shown to resist degradation by renal
      dehydropeptidase I. In a multicenter, open-label, prospective trial, we compared
      the efficacy and safety of meropenem with imipenem/cilastatin in patients with
      skin and soft tissue infections. Patients received either 500 mg of meropenem
      every 8 hours (n = 184) or 500 mg of imipenem/cilastatin every 6 hours (n = 193),
      by intravenous infusion for an average of 6 to 7 days. Satisfactory clinical
      responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients
      and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients.
      Satisfactory bacteriologic responses were achieved in 120 (98%) of 123 assessable
      meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin
      treated patients. Satisfactory bacteriologic response rates were high as well:
      94% with meropenem and 91% with imipenem/cilastatin. Between-group differences in
      satisfactory response rates were not significant (95% confidence interval, -2.29
      to 6.93 [clinical]; -2.73 to 10.39 [bacteriologic]). Overall pathogen eradication
      rates (for aerobes and anaerobes) were slightly higher for meropenem. Elevated
      liver enzymes were the most frequent adverse events in each treatment group.
      Meropenem was well tolerated and as effective as imipenem/cilastatin in treatment
      of hospitalized patients with skin and soft tissue infections.

PMID- 7716591
TI  - Blastomycosis: pulmonary and pleural manifestations.
AB  - Seven diverse cases of pulmonary blastomycosis were recently diagnosed at this
      institution. It is our purpose to review the unique features in the spectrum of
      this systemic illness as illustrated by these cases. The wide range of
      radiographic findings included parenchymal disease, mass-like lesions, and
      pleural effusions. One patient had endobronchial blastomycosis. Although
      significant pleural effusions have been uncommonly reported, we note this finding
      in two of our seven cases. Both of these patients had thoracentesis, which
      yielded markedly elevated pleural fluid total protein. These seven cases
      emphasize the marked variability of pulmonary and pleural blastomycosis.

PMID- 7716592
TI  - Incidence of neonatal circumcision in Atlanta, 1985-1986.
AB  - We reviewed Atlanta area hospital records to determine the following regarding
      neonatal circumcision: incidence in July 1985; incidence after publicized serious
      complications of circumcision in August 1985; medical record documentation; and
      the complication rate. After stratified sampling from hospital birth logs, we
      abstracted information from medical charts and calculated weighted estimates and
      P values. The circumcision incidence was 89.3% in July 1985, 87.5% in September
      1985, and 84.3% in September 1986. Circumcision was recorded on the medical
      record face sheet for 84.3% of circumcised boys. The complication rate was 3.1%;
      no serious complications were recorded. We conclude the following: circumcision
      incidence was high during the study period; publicity regarding adverse outcomes
      may have decreased the subsequent incidence of the procedure; hospital discharge
      data, which rely on medical record face sheet information, underestimate the true
      incidence of neonatal circumcision; and neonatal circumcision is usually safe,
      but serious complications may occur.

PMID- 7716593
TI  - D-dimer test for early detection of HELLP syndrome.
AB  - We attempted to predict patients at risk for HELLP syndrome (hemolysis, elevated
      liver enzymes, and low platelet count) by using the D-dimer test to screen 81
      preeclamptic gravidas and 12 control subjects. Among preeclamptic patients, 43
      had positive and 38 had negative results of D-dimer tests. All controls had
      negative results. Women with positive results had significantly higher mean
      arterial pressures at admission and postpartum, lower platelet counts, and
      elevated liver enzyme values. D-dimer-positive women also had infants with
      significantly lower birth weight and lower Apgar scores. After delivery, those
      with a positive D-dimer test were at risk for even greater abnormalities of liver
      enzymes, as well as lower platelet counts. Abnormalities of any of these
      laboratory parameters were unlikely in the presence of a negative D-dimer test
      result (negative predictive value = 0.89). Our results suggest that D-dimer
      positive preeclamptic women are at high risk of having HELLP syndrome and should
      receive close follow-up, whereas D-dimer-negative patients are unlikely to have
      this disorder and tend to have a better maternal-fetal outcome.

PMID- 7716594
TI  - Fluoroscopically guided nasoenteric feeding tube placement versus bedside
      placement.
AB  - In debilitated patients, establishment of adequate nutritional status is
      important to decrease morbidity and mortality. The objective of this study is to
      compare the relative benefits and costs of bedside placement of enteric feeding
      tubes to fluoroscopic placement. We did a 4-year retrospective study of 328
      nasoenteric feeding tube placements. Radiology department computer and chart
      reviews were done to identify patients, determine the time to successful
      placement of the tube, and define when adequate nutritional intake was obtained
      through the enteric feeding tube. We evaluated relative costs, time to placement,
      repeat rate, and complications. Our findings show that fluoroscopic placement of
      nasoenteric tubes had fewer complications and allowed earlier feeding. For
      patients in whom immediate nutritional supplementation is needed and for whom the
      risk of aspiration is high, fluoroscopically placed feeding tubes are more cost
      effective, quicker, and more successful than blind bedside placement.

PMID- 7716595
TI  - Profile of HIV disease in an American border city.
AB  - A previous study on patterns of migration of HIV-infected persons suggested that
      most patients in a rural setting in eastern Tennessee acquired their disease in
      an urban area, typically during a period of prolonged residence. Disease and
      disability were the most common reasons for returning to their hometown. We
      studied our urban, border-city HIV clinic population to see whether similar
      patterns of migration were discernible. Fifty-one of the 103 patients studied
      lived outside the El Paso/Juarez area when they contracted HIV infection. The
      major reason cited for returning home was a desire to return to family (25%).
      Those who returned and those who had never left showed no statistically
      significant difference in age, race, or risk factors. This study suggests that
      migration of HIV-infected patients back to their hometown does not appear to be
      an exclusively rural phenomenon.

PMID- 7716597
TI  - Epidemiology of cleft lip and cleft palate in Mississippi.
AB  - We present an epidemiologic study of the cases of cleft lip and cleft palate in
      Mississippi from 1980 through 1989. Cases were stratified by race (white and
      nonwhite) but not by association with a major malformation. During this period, a
      total of 457 new patients with cleft lip or cleft palate were identified from a
      population of approximately 439,354 live births. The incidence of total clefts in
      live-born infants was 1.36/1,000 for whites and 0.54/1,000 for nonwhites. White
      boys had a higher incidence of cleft lip and palate than white girls; black boys
      had an extremely low incidence of cleft lip, whereas black girls showed a higher
      incidence of cleft palate alone. Examination of the rate of cleft malformations
      for each county in Mississippi revealed no clearly defined pattern, nor were we
      able to demonstrate that rates were increased in a major agricultural area of the
      state, in which use of potentially toxic products is high.

PMID- 7716596
TI  - Inguinal wound fluid collections after vascular surgery: management by early
      reoperation.
AB  - Inguinal wounds complicated by significant fluid collections after vascular
      grafting procedures were managed by exploration soon after recognition in 14
      patients. Within 24 hours, incisions were reexplored, fluid collections were
      evacuated and cultured, and closed suction drains were placed. The wound was
      reapproximated, and broad spectrum antibiotics were given intravenously until 24
      hours after removal of the drain. Variables evaluated included spontaneous
      drainage before exploration, positive intraoperative wound cultures, exposure of
      graft when the wound was opened, and type of graft used. On careful follow-up,
      from 5 months to 3.5 years, averaging 14 months, only one patient had an infected
      graft, occurring 6 months after the wound exploration. There were no
      complications in wound healing from the inguinal explorations. These results
      suggest that early exploration and reclosure of clinically significant
      postoperative fluid collections is safe, results in primary healing, and has a
      low rate of subsequent graft infection.

PMID- 7716598
TI  - Forced expiratory flow is reduced by 100% oxygen in patients with chronic
      obstructive pulmonary disease.
AB  - In order to determine the effect of breathing high fractional concentrations of
      oxygen on forced expiratory flow in individuals with chronic obstructive
      pulmonary disease (COPD), we studied 18 patients with moderately severe disease.
      The patients were studied breathing air, 100% oxygen, or a four-gas mixture in a
      randomized double-blind study design. The four-gas mixture (oxygen 21.0%, argon
      48.6%, nitrogen 19.3%, and helium 11.1%) was calculated to have a density and
      viscosity similar to oxygen. During spirometric testing, breathing oxygen
      produced a detectable reduction in timed volumes by 1 minute that was sustained
      at 5 minutes (FEV1 reduction 4.9% at 1 minute and 6.3% at 5 minutes). Breathing
      the gas mixture for 5 minutes resulted in similar reductions in flow. We conclude
      that high concentrations of oxygen reduce forced expiratory flow in patients with
      airflow obstruction, an effect probably related to the increased density and
      viscosity relative to air. This reduction in forced expiratory flow may
      contribute to the deterioration seen when COPD patients with acute respiratory
      failure are treated with 100% oxygen.

PMID- 7716599
TI  - Ventral hernia and other complications of 1,000 midline incisions.
AB  - We report the outcome in 1,079 consecutive clean or clean-contaminated midline
      abdominal incisions closed with running 0-loop nylon suture after both elective
      and emergency operations done between 1984 and 1991. Postoperatively, 79 patients
      were lost to follow-up, resulting in 1,000 having long-term follow-up. Mean
      follow-up among these patients was 22 months. Early wound complications included
      subcutaneous wound infection (18), deep wound infection (17), dehiscence (13),
      fistula (2), and suture sinus (2). A ventral hernia developed in 42 (4.2%) cases
      during follow-up. By chi-square analysis, wound infection, dehiscence, class of
      clean-contaminated wound, patient age > 65, or previous midline abdominal
      incision were not identified as risk factors for development of a ventral hernia.
      Reuse of a previous midline incision in combination with any wound infection was
      associated with an increased risk of subsequent ventral hernia (stepwise
      regression). In our experience, running closure of a vertical midline abdominal
      wound has not been associated with an excessive incidence of wound complications
      or of ventral hernia.

PMID- 7716600
TI  - Pseudoepitheliomatous hyperplasia mistaken for cancer after delayed
      reconstruction.
AB  - Pseudoepitheliomatous hyperplasia (PEH) arises in areas of chronic inflammation
      and can be mistaken for squamous cell carcinoma, leading to unnecessary removal
      of more tissue. We present a study of 21 patients having delayed reconstruction
      of defects left by Mohs micrographic surgery (MMS) to remove facial skin cancers.
      Reconstruction was done at an average of 6 days after MMS. Four of these 21
      patients (19%) had PEH in the wound margins. Presence of PEH did not correlate
      with age, sex delay in reconstruction, frequency of wound care, size or location
      of the defect, type of tumor, or smoking status. During an average 24-month
      follow-up, none of these four patients had tumor recurrence, suggesting that the
      benign diagnosis of PEH was correct. We detail the histologic features of PEH,
      and describe techniques for minimizing confusion with squamous cell carcinoma.

PMID- 7716602
TI  - Candidemia after endoscopic retrograde cholangiopancreatography.
AB  - We report a case of candidemia associated with manipulation of the common bile
      duct during endoscopic retrograde cholangiopancreatography. The patient had
      received parenteral nutrition and prolonged antibiotic therapy before the
      procedure and before Candida tropicalis was grown from blood cultures. Antifungal
      therapy resulted in clinical response.

PMID- 7716601
TI  - Supplemental oxygen and gastric pH in unfed preterm infants.
AB  - Hypoxia has been associated with decreased gastric acidity in infants and
      children. In neonates, an inverse relationship between gestational age and
      gastric acidity may confound this association. To assess the relationship between
      oxygen supplementation and gastric acidity in premature neonates, mean 24-hour
      continuous measurements of gastric pH, obtained by an indwelling flexible gastric
      pH probe, were compared in infants requiring and not requiring oxygen. Patients
      were < 36 weeks' gestational age and were unfed before and during the assessment
      period. The gestational age of infants who required oxygen was less than that of
      infants who did not (30.5 +/- 3.0 vs 32.9 +/- 1.5 weeks, respectively). Other
      comparison variables were not different. The mean pH for infants requiring oxygen
      (4.4 +/- 1.7) was significantly greater than that of those not needing oxygen
      (2.7 +/- 1.2). After controlling for population characteristics and gestational
      age, we found that infants requiring oxygen still had significantly reduced
      gastric acidity.

PMID- 7716603
TI  - Subdural injection of a local anesthetic with steroids: complication of epidural
      anesthesia.
AB  - We describe the unintentional injection of a small amount of local anesthetic
      with steroids into the subdural space during an attempted lumbar epidural
      injection for low back pain. When small volumes of local anesthetic are injected
      into the subdural space, a patchy and unilateral block of greater magnitude than
      expected will result. When larger volumes of local anesthetic are injected, a
      massive motor and sensory block can occur due to the small confines of this
      space. Accidental subdural injection must be recognized early and treated
      appropriately to avoid serious complications, especially in an outpatient
      setting.

PMID- 7716604
TI  - Cerebral vasculitis complicating rheumatoid arthritis.
AB  - Central nervous system vasculitis is a rarely described complication of
      rheumatoid arthritis. We report a case of cerebral vasculitis in a 55-year-old
      woman with a 7-year history of seropositive, nodular rheumatoid arthritis.
      Striking multifocal abnormalities of the white matter on magnetic resonance
      imaging led to a suspicion of vasculitis despite lack of clinical evidence of
      extracranial vasculitis and normal findings on cerebrospinal fluid studies and
      cerebral angiography. After institution of treatment with glucocorticoids and
      azathioprine, she survived in stable condition for 14 months from the onset of
      symptoms. Postmortem examination of the brain revealed vasculitis and chronic
      ischemic changes.

PMID- 7716605
TI  - Compound adrenal medullary tumor.
AB  - Compound tumors of the adrenal medulla, characterized by a mixture of
      pheochromocytoma and ganglioneuroma, are rare, only 12 cases having been reported
      in the literature. We present the case of a 66-year-old woman with a left-sided
      incidentally discovered adrenal mass that was subsequently shown to contain
      elements of pheochromocytoma and ganglioneuroma. The patient had no history of
      hypertension but did have a history of "idiopathic" edema (dependent edema). A
      review of the literature shows hormonal hypersecretion in approximately three
      fourths of the reported cases. Because of the preoperative hypertensive crises
      from the pheochromocytoma component of the tumor, contemporary management of
      incidentally discovered adrenal masses must include preoperative hormonal
      evaluations to exclude endocrine hyperfunction.

PMID- 7716606
TI  - Circulating xanthine oxidase in human ischemia reperfusion.
AB  - Reactive oxygen species (ROS) generated from xanthine oxidase (XO) play an
      important role in ischemia-induced injury. We hypothesize that XO and xanthine
      dehydrogenase (XDH) are released into the circulation with ischemia reperfusion
      to the human liver and intestine. Blood was drawn from a patient, before and at
      intervals after an aortic cross-clamp procedure. Plasma was incubated in the
      presence of xanthine, with NAD+ (for XD +XO) and without NAD+ (for XO). The
      amount of urate formed was quantified using a high-performance liquid
      chromatograph (HPLC). The calculated XDH+XO and XO activity increased from 1.88
      and 1.66 microU/mg protein, respectively, before the cross clamp to 3.77 and 3.11
      microU/mg, respectively, 7 minutes after reperfusion to the superior mesenteric,
      celiac, and right renal artery beds. The release of a significant biological
      source of ROS may explain the damage to lung or heart observed after ischemia to
      the human liver and intestine.

PMID- 7716607
TI  - Spontaneous pneumomediastinum in a patient with diabetic ketoacidosis: a
      potentially hidden complication.
AB  - A pediatric patient with diabetic ketoacidosis (DKA) was found to have a
      pneumomediastinum and a small pneumothorax. Because some of the signs and
      symptoms of pneumomediastinum may be confused with those of the patient's primary
      disease process, this complication may be present more frequently than has been
      previously described.

PMID- 7716608
TI  - Iatrogenic transplantation of osteosarcoma.
AB  - We report a case in which a patient having curettage and resection of a presumed
      benign lesion of the tibia (later recognized as osteosarcoma) had probable
      iatrogenic transplantation of tumor to the contralateral iliac crest, which had
      served as a donor site for bone chips used to pack the tibial lesion. The patient
      later had above-knee amputation for the primary tumor and eventually required
      contralateral hemipelvectomy when tumor developed in the iliac crest donor site.
      We discuss the literature of tumor transplantation and seeding in operative
      settings and stress the clinical importance of avoiding possible tumor
      contamination of operative fields by meticulous instrument changes and by
      isolation of multiple surgical fields.

PMID- 7716609
TI  - Vitiligo and alopecia areata in patients with human immunodeficiency virus
      infection.
AB  - In patients infected with human immunodeficiency virus (HIV) the development of
      autoimmune diseases, while not life threatening, is an interesting phenomenon
      that may result from immune dysfunction or from B cell infection by HIV, Epstein
      Barr virus, or other unknown viruses. Vitiligo and alopecia areata are among the
      autoimmune diseases that have been reported in 11 patients infected with HIV. We
      describe a 47-year-old man who had vitiligo and alopecia areata approximately 2
      years after testing positive for HIV antibodies.

PMID- 7716610
TI  - Marked deterioration in glycemic control with change in brand of lactulose syrup.
AB  - Lactulose is a poorly absorbed synthetic disaccharide frequently used in the
      treatment of portasystemic encephalopathy. Because lactulose syrup contains small
      amounts of absorbable sugars, it may cause hyperglycemia in diabetic individuals,
      but is usually well tolerated. We report the case of a patient with diet
      controlled diabetes and cirrhosis who experienced a marked deterioration in
      glycemic control, requiring insulin use, when he began using a different brand of
      lactulose syrup. The hyperglycemia resolved and insulin was discontinued after
      use of the original brand of lactulose syrup was resumed.

PMID- 7716611
TI  - Solitary plasmacytoma of the sacrum presenting as a pelvic mass: report of two
      cases.
AB  - We describe two unusual cases of solitary plasmacytoma of the sacrum seen as a
      pelvic mass. Excessive bleeding, a distinct possibility, should be anticipated
      whenever a biopsy or resection of the tumor is considered. Because of the tumor's
      apparent radioresponsiveness and known evolution to multiple myeloma in some
      cases, radiotherapy and chemotherapy are recommended.

PMID- 7716613
TI  - Malignant melanoma: a major cancer hazard for the 21st century.

PMID- 7716612
TI  - Rapid reocclusion of left primary bronchus by fibrinomucinous cast in a case of
      large cell lung cancer.
AB  - This report describes a case of large cell carcinoma of the lung in a patient
      whose left primary bronchus became completely occluded by a fibrinomucinous cast
      that recurred within 24 hours despite extensive lavage and removal of the cast
      via flexible bronchoscopy. The primary tumor involved the aortopulmonary window
      and was affixed to the pulmonary artery and the aorta, arising from the left
      upper lobe and extending to the left primary bronchus. The occurrence of a large
      fibrinous endobronchial cast removed by flexible bronchoscopy forceps, such as we
      report here, is extremely rare.

PMID- 7716614
TI  - Report of a new technique for replacement of umbilical arterial catheters in very
      low birth weight (VLBW) neonates.

PMID- 7716615
TI  - Heparin-associated thrombocytopenia with thrombosis.

PMID- 7716616
TI  - Comparative anatomy of the baboon and the human cervical spine.
AB  - STUDY DESIGN: The anatomy of baboon and human cervical spines were compared by
      measuring adult, cadaveric specimens. OBJECTIVE: The objective of the study was
      to compare human and baboon cervical motion segments to determine whether the
      baboon provides a suitable model for spinal research. SUMMARY OF BACKGROUND DATA:
      Several studies have examined the quantitative anatomy of the human cervical
      bones and ligaments. Several animal species have been used for cervical spine
      research; however, no studies have validated whether the animal models resemble
      the human cervical spine closely enough to provide generalizable data. METHODS:
      Multiple morphologic parameters were measured directly from nine baboon and six
      human adult cadaveric cervical spine specimens. The bone structure and geometry
      of each of the seven cervical vertebrae were analyzed; the structure and
      histology of the ligaments were measured; and histomorphometry of the vertebrae
      was performed. RESULTS: The architectural composition and geometry of individual
      cervical vertebrae of baboons and humans were similar at each level. The
      proportional relationship of bone and ligament structures in the two species was
      almost identical. There were, however, several differences: 1) The baboon spine
      was about half the size of the human spine; 2) its vertebral arteries were
      encased fully within the C1 lateral mass; 3) its uncovertebral joints were more
      prominent; 4) its vertebral endplates were more concave; 5) its pedicles were
      thinner; 6) its transverse processes were longer; and 7) its spinous processes
      were horizontal and nonbifid. CONCLUSIONS: The geometry and anatomy of the baboon
      cervical spine closely resemble that of the human cervical spine. It therefore
      provides an excellent model for in vivo and in vitro research.

PMID- 7716617
TI  - A rapid transport route between the epidural space and the intraneural
      capillaries of the nerve roots.
AB  - STUDY DESIGN: The possibility of epidurally applied substances reaching the
      intraneural capillaries of the spinal nerve roots and cauda equina was assessed
      in the pig sacrococcygeal spine. METHODS: The presence of Evans blue-labelled
      albumin in intraneural capillaries after epidural application for 1, 10, or 30
      minutes was studied with fluorescence microscopy. Ink angiography was used to
      determine whether there were any direct communicating vessels between the
      epidural vein plexus and the intraneural capillaries. RESULTS: Evans blue
      labelled albumin was present in the intraneural capillaries 1 minute after
      epidural application. Microangiography demonstrated small venules that connected
      the epidural vein plexus and the intraneural capillaries. CONCLUSIONS: The
      results of this study demonstrated a rapid transport route between the epidural
      space and the intraneural capillaries. The results suggest that nucleus pulposus
      material, as well as epidurally applied substances, such as local anesthetic
      drugs or epidurally injected corticosteroids, may have a rapid, direct transport
      route to the axons of the spinal nerve roots. The demonstrated transport route
      also may be related to the mechanisms behind epidural anesthesia and spinal nerve
      root infiltration.

PMID- 7716618
TI  - Measurement of vertebral cortical integrity during pedicle exploration for
      intrapedicular fixation.
AB  - STUDY DESIGN: This study determined the predictive ability of electrical
      impedance measurement in detecting cortical perforation in a porcine model of
      pedicular exploration. OBJECTIVE: This study tested the hypothesis that a large
      decrease in electrical impedance would occur as a result of perforation of the
      vertebral cortex by the pedicle probe. SUMMARY OF BACKGROUND DATA: The
      resistivity of cortical bone has been reported to be 25 to 100 times greater than
      that of soft tissues. METHODS: A total of 42 pedicles of the lumbar spines of six
      swine were explored using the instrumented pedicle probes. RESULTS: Using a 1
      microAmp 30-Hz current source, measurement of electrical impedance predicted
      cortical rupture with a sensitivity, specificity, and accuracy of 95%. Maximum
      applied voltages of 2.8 mV did not result in myogenic stimulus. CONCLUSIONS:
      Electrical impedance measurement provides an accurate real-time measurement of
      cortical perforation. This technique is adapted readily for use with pedicular
      screws and screw tape. Further investigation to determine the clinical use of
      this technique is recommended.

PMID- 7716619
TI  - Fatigue of the erector spinae muscles. A quantitative assessment using "frequency
      banding" of the surface electromyography signal.
AB  - STUDY DESIGN: The authors investigated fatigue-induced changes in the frequency
      content of the surface electromyographic (EMG) signal from the erector spinae
      muscles. OBJECTIVES: The objective of the study was to understand the EMG changes
      in fatiguing muscle and to obtain a reliable index of fatigue. SUMMARY OF
      BACKGROUND DATA: Power spectral analysis has been used increasingly in recent
      years to monitor muscle fatigue, but parameters other than the mean or median
      frequency have received little attention. METHODS: Thirty-five healthy volunteers
      participated. They pulled upward with constant force on a handlebar attached to a
      floor-mounted load cell while the EMG signal from the erector spinae was recorded
      at the levels of T10 and L3 at 1024 Hz; 1.0-sec "windows" of the signal were
      analyzed using fast Fourier transforms, and the resulting power spectra were
      divided into 10 frequency bands between 5 Hz and 300 Hz. The median frequency,
      total power, and peak amplitude of the spectra were also calculated. Changes in
      the frequency content of the EMG signal were examined during submaximal
      contractions of different intensity and duration. RESULTS: Median frequency
      decreased steadily during the contractions, whereas total power and peak
      amplitude increased. The most repeatable and linear index of change was the
      increase in the EMG signal in the 5-30 Hz frequency band. The middle-to-high
      frequency component of the EMG signal increased during the early stages of the
      contractions, but decreased as the endurance limit was approached. CONCLUSIONS:
      Changes in the 5-30 Hz band of the EMG power spectrum provide a more reliable and
      linear index of fatigue in the erector spinae muscles than do changes in median
      frequency. In the erector spinae, the early effects of fatigue appear to be
      delayed by the recruitment of additional motor units.

PMID- 7716620
TI  - Human trunk strength profile in flexion and extension.
AB  - STUDY DESIGN: Isometric and isokinetic trunk flexion-extension strengths were
      studied among 73 subjects (41 males and 32 females) and 10 patients (9 males and
      1 female). The isometric strengths were measured in four postures of trunk
      flexion. The isokinetic trunk strengths were measured through the range of these
      postures. OBJECTIVES: The study had two objectives: to develop a database for
      isometric flexion-extension strength at different levels of trunk flexion and
      isokinetic strength at corresponding angles and to determine the decrement in
      strength characteristics among patients of idiopathic low back pain. SUMMARY OF
      BACKGROUND DATA: Though flexion-extension strength among normal subjects and
      patients has been studied, its variation due to standardized postural change has
      not been reported extensively. The influence of postural deviation on flexion
      extension ratios are also largely unknown. METHODS: To achieve the objectives of
      the study, a device flexion-extension-lateral flexion tester (FELT) was designed
      and fabricated. The male and female subjects performed isometric flexion and
      extension at 0 degree, 20 degrees, 40 degrees and 60 degrees of trunk flexion;
      and isokinetic flexion starting at neutral posture, and isokinetic extension
      starting at 60 degrees of trunk flexion. The patients performed isometric flexion
      and extension in neutral posture only; and isokinetic flexion-extension similar
      to normal sample. RESULTS: The average strength in each activity was between 70
      and 80% of the corresponding peak strength. The isokinetic activity strengths
      ranged between 60 and 70% of the corresponding isometric activities in each
      group. The strength of females ranged between 60 and 70% of males. The ANOVA
      revealed that posture had a significant effect on strength. The multiple
      regression explained 73% of variance in isometric and 34% in isokinetic modes.
      CONCLUSIONS: A patient's strength profile should be determined in a posture that
      simulates activities of daily living to determine impairment and plan
      rehabilitation.

PMID- 7716621
TI  - Human trunk strength profile in lateral flexion and axial rotation.
AB  - STUDY DESIGN: To determine the functional capability in asymmetric trunk motion,
      isometric and isokinetic lateral flexion and axial rotation strengths of a normal
      and patient samples were measured. Seventy-three normal asymptomatic subjects (41
      males and 32 females) and ten patients (9 males and 1 female) were tested.
      OBJECTIVES: The dual objectives of the study were to develop a database for
      isometric and isokinetic lateral flexion and axial rotation strength capabilities
      of a normal sample and to determine the functional impairment of a sample of
      patients. SUMMARY OF BACKGROUND DATA: More than 60% of low back injuries are
      associated with trunk twisting. Asymmetric motions are important risk factors.
      However, strength capability data for axial rotation are sparse and those for
      lateral flexion nonexistent. METHODS: To achieve the objectives of the study, two
      devices were designed and fabricated. Isometric lateral flexion was tested
      bilaterally in neutral posture and at 10 degrees, 20 degrees, and 30 degrees of
      lateral bending. Isometric axial rotation was tested bilaterally in neutral
      posture and at 5 degrees, 10 degrees, 15 degrees, and 20 degrees of axial
      rotation. Isokinetic lateral flexion and axial rotation strengths were tested
      bilaterally starting from the neutral posture. RESULTS: The strength invariably
      declined progressively for all groups with increasing postural asymmetry. The
      strength in isokinetic activities ranged between 60% to 70% of the strength
      measured in isometric activities. All groups were significantly stronger in
      lateral flexion compared with axial rotation. The female sample ranged between
      60% to 70% values of males for all activities studied. The patient group was
      weakest, ranging between 45% to 55% for isometric and 52% to 58% for isokinetic
      activities of their control group.

PMID- 7716622
TI  - In vivo measurement of lumbar spinal creep in two seated postures using magnetic
      resonance imaging.
AB  - STUDY DESIGN: A magnetic resonance imaging technique was developed to measure
      creep in the lumbar spine in different seated postures. Owing to the fixed size
      and horizontal orientation constraints of the magnetic resonance imaging system
      bore, gravitational force was simulated in the horizontal plane while the subject
      assumed each of two near-seated postures: 1) flexed lumbar, and 2) extended
      lumbar. OBJECTIVES: One experimental subject was used to determine the
      feasibility of this technique designed to correlate spinal creep with different
      seated postures. SUMMARY OF BACKGROUND DATA: Although epidemiologic and
      pathologic studies have linked the seated posture with low back pain and disc
      degeneration, few in vivo studies have explored the mechanical response of the
      lumbar spine to seated postures. METHODS: Creep displacement of four lumbar discs
      (L3-S1) was measured from unloaded and loaded scans separated by 30 minutes of
      constant loading. Forty-eight images were measured from three trials in each
      posture, four sagittal slices per trial. RESULTS: Creep while in an extended
      posture (3.58 mm) was greater than creep while in a flexed posture (2.92 mm).
      System resolution was 0.78 mm. CONCLUSION: This technique can be used to discern
      between creep displacements in different postures.

PMID- 7716623
TI  - The effects of lateral trunk bending on muscle recruitments when resisting
      nonsagittally symmetric bending moments.
AB  - STUDY DESIGN: Surface electromyographic activities were measured in 15 subjects
      as they maintained a static laterally bent trunk posture and resisted sagittally
      symmetric and asymmetric moments applied to their torsos. The moment magnitudes
      were 20 and 40 Nm and had transverse plane directional components in 30 degrees
      increments surrounding the subjects' torsos. OBJECTIVES: To quantify the
      myoelectric responses from eight trunk muscles as asymmetric loads were applied
      to the laterally bent torso. SUMMARY OF BACKGROUND DATA: Asymmetric material
      handling frequently results in lateral bending of the torso. Each of these
      factors have been linked via epidemiologic investigations to the incidence of low
      back disorders. Little information is available that describes the response of
      the trunk muscles when the trunk is bent to the side. METHODS: Subjects stood in
      a reference frame and adjusted their trunk posture to marks on a video display
      that indicated when a 20 degrees lateral bend to the right had been achieved.
      Moments were applied to the torso by connecting weights via cables and pulleys to
      a chest harness. Electromyographic activities were recorded bilaterally from the
      erector spinae, latissimus dorsi rectus abdominis, and external oblique muscles.
      RESULTS: The electromyographic data indicated that the muscles showed the
      greatest activity when they were in opposition to the applied sagittal and
      frontal plane moments. The left external oblique showed the greatest response and
      was sensitive to the widest range of moment direction conditions. All of the
      muscles, except for the left latissimus dorsi, at times contributed antagonistic
      moments in the sagittal plane or the frontal plane, or in both planes. These data
      were compared with previously obtained data from an upright neutral posture.
      CONCLUSIONS: Statistical analyses indicated that the responses of both external
      obliques and the left erector spinae to the moment direction conditions were
      significantly different between the laterally bent and neutral postures.

PMID- 7716624
TI  - Stability increase of the lumbar spine with different muscle groups. A
      biomechanical in vitro study.
AB  - STUDY DESIGN: This study investigated the influence of five different muscle
      groups on the monosegmental motion (L4-L5) during pure flexion/extension, lateral
      bending, and axial rotation moments. OBJECTIVES: The results showed and compared
      the effect of different muscle groups acting in different directions on the
      stability of a single motion segment to find loading conditions for in vitro
      experiments that simulate more physiologically reasonable loads. SUMMARY OF
      BACKGROUND DATA: In spine biomechanics research, most in vitro experiments have
      been carried out without applying muscle forces, even though these forces
      stabilize the spinal column in vivo. METHODS: Seven human lumbosacral spines were
      tested in a spine tester that allows simulation of up to five symmetrical muscle
      forces. Changing pure flexion/extension, lateral bending, and axial rotation
      moments up to +/- 3.75 Nm were applied without muscle forces, with different
      muscle groups and combinations. The three-dimensional monosegmental motion was
      determined using an instrumented spatial linkage system. RESULTS: Simulated
      muscle forces were found to strongly influence load-deformation characteristics.
      Muscle action generally decreased the range of motion and the neutral zone of the
      motion segments. This was most evident for flexion and extension. After five
      pairs of symmetrical, constant muscle forces were applied (80 N per pair), the
      range of motion decreased about 93% in flexion and 85% in extension. The total
      neutral zone for flexion and extension was decreased by 83% muscle action. The
      multifidus muscle group had the strongest influence. CONCLUSION: This experiment
      showed the importance of including at least some of the most important muscle
      groups in in vitro experiments on lumbar spine specimens.

PMID- 7716625
TI  - Relative lumbar and pelvic motion during loaded spinal flexion/extension.
AB  - STUDY DESIGN: This study analyzed relative lumbar and pelvic motion during
      sagittal plane trunk motion. Patterns of movement were compared during loaded
      trunk flexion and extension. OBJECTIVES: The purpose of this study was to examine
      the dynamic relationship between the lumbar spine and pelvis during trunk motion
      and to determine the effect of direction of lift (up vs. down) on lumbar-pelvic
      rhythm. SUMMARY OF BACKGROUND DATA: There is disagreement in the literature
      regarding whether rotations of the pelvis and lumbar spine occur sequentially or
      simultaneously during bending and lifting tasks. METHODS: Thirty healthy women,
      ranging in age from 19 to 35 years, participated in the study. The 3Space Tracker
      System, an electromagnetic tracking device, was used to monitor simultaneous
      lumbar and pelvic motion as subjects lifted and lowered a 9.5 kg box with knees
      extended. RESULTS: Although lumbar and pelvic motion occurred simultaneously
      during flexion and extension, there was greater separation of these movements
      during the "up lifts" than during the "down lifts." CONCLUSIONS: Lumbar-pelvic
      rhythm varied depending on whether the trunk was flexing or extending. During
      trunk flexion (down lift) there was a greater tendency for lumbar and pelvic
      rotations to occur simultaneously, whereas during extension (up life) they tended
      to occur more sequentially.

PMID- 7716626
TI  - Ossification of the posterior longitudinal ligament. Autosomal recessive trait.
AB  - STUDY DESIGN: This study analyzed the mode of inheritance of ossification of the
      posterior longitudinal ligament (OPLL) from the pedigree of a family. OBJECTIVES:
      The results were correlated to provide a new mode of inheritance of OPLL. SUMMARY
      OF BACKGROUND DATA: Although a nation-wide multicenter survey of OPLL has been
      carried out in 347 subjects and 1030 relatives in Japan since 1981, no parental
      consanguinity has been reported. METHODS: In the family, three siblings and one
      other member of a family underwent operations for OPLL in our department, and the
      clinical information regarding other family members was obtained from interviews
      with these four patients or relatives. RESULTS: The parents of three affected
      siblings and another unaffected sister were first cousins, and the father was
      suspected to be affected as well. CONCLUSION: Transmission of OPLL as an
      autosomal recessive trait in this family, which has not been reported, is
      suspected; although, the possibility that it is a dominant trait can not be
      excluded.

PMID- 7716627
TI  - Subaxial lesions in rheumatoid arthritis. Radiographic factors suggestive of
      lower cervical myelopathy.
AB  - STUDY DESIGN: The present study focused on the radiographic and clinical
      parameters that suggest lower cervical lesions directly or indirectly related to
      lower cervical myelopathy in rheumatoid arthritis. OBJECTIVES: The results
      provided the risk factor for predicting compressive myelopathy due to lower
      cervical spine lesions in patients with rheumatoid arthritis. SUMMARY OF
      BACKGROUND DATA: The clinical pathology and radiographic risk factor for upper
      cervical myelopathy in rheumatoid arthritis has been well documented, but the
      compressive factors for lower cervical myelopathy due to subaxial lesions remain
      unclear. METHODS: Radiographic analysis on the lateral radiographs (neutral,
      flexion, and extension) of the cervical spine and neurologic evaluation were
      carried out in 100 patients with rheumatoid arthritis. Fifty-eight of these
      patients were followed-up for 5 to 10 years (mean, 5.4 years) radiographically
      and clinically. A comparative study on the incidence of radiographic
      abnormalities also was performed in 100 patients with rheumatoid arthritis and in
      age- and sex-matched patients with cervical spondylosis. CONCLUSIONS: Among the
      radiographic parameters of the lesions related to lower cervical myelopathy,
      marked destruction of spinous processes, axial shortening, and narrow spinal
      canal may be important factors that suggest myelopathy. Time-related
      deterioration of lower cervical myelopathy can be predicted by progressions of
      anterior slip, axial shortening, spinous process erosion, apophysial joint
      erosion, and intervertebral disc collapse. Younger patient age, longer duration
      of disease, higher dose of corticosteroid administration, and higher stage or
      class of rheumatoid arthritis also are thought to be significant general factors
      for myelopathy.

PMID- 7716628
TI  - Frameless stereotactic guidance. An intraoperative adjunct in the transoral
      approach for ventral cervicomedullary junction decompression.
AB  - METHODS: The application of a video-interactive frameless stereotactic guidance
      system for the treatment of ventral cervicomedullary junction compression is
      described in a patient with basilar invagination, odontoid dysgenesis, and a
      Chiari malformation who had irreducible impingement on the ventral brainstem by a
      partially fused mass of bone made up of the malformed odontoid peg, the inferior
      clivus, and dorsally protruding osteophytes at the odontoid-clival junction.
      RESULTS: This technology permitted instantaneous feedback of the surgeon's
      orientation in all planes, facilitating extensive removal of the dens and clival
      tip to achieve adequate ventral brainstem decompression. In view of the
      distortion of the craniovertebral anatomy produced by the patient's anomalies,
      the ability to visualize three dimensionally the location of the vertebral
      arteries also added an element of safety to the lateral bone removal. Similarly,
      the ability to localize the rostral limit of the clivus that needed to be
      resected and the caudal extent of C2 that needed to be removed to achieve an
      adequate decompression helped ensure that the extent of bone removal was
      appropriately tailored to the patient's anatomy. CONCLUSION: The authors believe
      this technique represents a significant advance over standard radiographic
      intraoperative localization techniques during transoral approaches to the ventral
      cervicomedullary junction for patients in whom the odontoid is fixed in position
      in relation to the clivus. This is based on the speed with which localization can
      be obtained, the accuracy of the information provided, the ability to obtain
      localization in multiple planes simultaneously, and the lack of radiation
      exposure during the procedure.

PMID- 7716629
TI  - Comparing the costs between provider types of episodes of back pain care.
AB  - STUDY DESIGN: This study was a prospective, community-based, observational
      design. OBJECTIVES: The authors compared the costs of episodes of back pain care
      between different provider types in a population representative of the U.S.
      SUMMARY OF BACKGROUND DATA: Previous comparisons between provider types of the
      costs for back pain care have been restricted to the worker's compensation
      population or have used something other than the episode as the unit of analysis.
      METHODS: Data from the RAND Health Insurance Experiment (HIE) were analyzed.
      Insurance claims forms were examined for all visits specified by the patient as
      occurring for back pain. Visits were grouped into episodes using decision rules
      and clinical judgment. The primary provider was defined as the provider who
      delivered most of the care. Comparisons of costs between provider types were
      made. RESULTS: There were 1020 episodes of back pain care made by 686 different
      persons and encompassing 8825 visits. Chiropractors and general practitioners
      were the primary providers for 40% and 26% of episodes, respectively.
      Chiropractors had a significantly greater mean number of visits per episode
      (10.4) than did other practitioners. Orthopedic physicians and "other" physicians
      were significantly more costly on a per visit basis. Orthopedists had the highest
      mean total cost per episode, and general practitioners the lowest. Chiropractors
      had the highest, and general practitioners the lowest mean outpatient cost per
      episode. CONCLUSIONS: These are economically significant differences in the costs
      of back pain care of persons seeing chiropractors, general practitioners,
      internists, and orthopedists.

PMID- 7716631
TI  - The use of the pain drawing as a screening measure to predict psychological
      distress in chronic low back pain.
AB  - STUDY DESIGN: The ability of three new methods of scoring the Pain Drawing to
      predict psychological distress in two cohorts of 100 patients with chronic low
      back pain was investigated. OBJECTIVES: Patients completed a Pain Drawing and
      questionnaire measures of psychological distress and were given a standard
      physical examination. SUMMARY OF BACKGROUND DATA: The two cohorts were
      significantly different on all variables (except for disability). METHODS: The
      relationship between the three new scoring systems and measures of distress,
      physical factors, and disability was investigated. RESULTS: The new scoring
      methods had high reliability. Pain Sites was a more accurate predictor of
      distress, but was unable to do so with sufficient specificity/sensitivity. Body
      Map did not correlate with physical/disability measures. CONCLUSION: Using the
      new scoring systems, it was not possible to identify distressed patients with
      sufficient sensitivity/specificity, nor to differentiate between organic and
      nonorganic pain patterns.

PMID- 7716630
TI  - Methodological quality of randomized clinical trials on treatment efficacy in low
      back pain.
AB  - STUDY DESIGN: This was a review of criteria-based meta-analyses. OBJECTIVES: To
      assess the methodological quality of published randomized clinical trials on the
      efficacy of commonly used interventions in low back pain. SUMMARY OF BACKGROUND
      DATA: During the last several decades, the number of published randomized
      clinical trials regarding low back pain has continued to grow. For some
      interventions, considerable numbers of trials are available. Trials have been
      shown to vary substantially regarding their quality. METHODS: A computer-aided
      search was conducted of published randomized clinical trials into the efficacy of
      spinal manipulation and mobilization, exercise therapy, back schools, bed rest,
      orthoses, and traction therapy. There was additional screening of journals not
      covered by Medline and Embase. The methodological quality of the studies was
      assessed using a set of predefined criteria. RESULTS: Sixty-nine different
      randomized clinical trials were identified. Methodological scores varied between
      16 and 82 points (maximum was 100 points). Methodological quality tended to be
      associated with the outcomes of the studies. Methodological shortcomings were
      frequently found--e.g., small sample sizes, no description of the randomization
      procedure, no description of drop-outs, no placebo-control group, and lack of
      blinded outcome assessments. CONCLUSIONS: Although a considerable number of
      randomized clinical trials have been carried out to evaluate the efficacy of
      interventions in low back pain, their methodological quality appears to be
      disappointingly low. Future trials are clearly needed, but much more attention
      should be paid to the methods of such studies.

PMID- 7716632
TI  - Brown-Sequard syndrome associated with Horner's syndrome in cervical epidural
      hematoma.
AB  - STUDY DESIGN: This report analyzed the likely locations of lesions that cause a
      combination of Horner's and Brown-Sequard syndromes. One must know the anatomic
      structure of spinal cord and the sympathetic nerve chain. OBJECTIVES: A
      hypertensive patient had Brown-Sequard and Horner's syndromes after neck trauma.
      The magnetic resonance imaging and surgical findings showed the correlation
      between the clinical symptoms and the likely lesion. METHODS: The patient
      underwent right hemilaminectomy from C2 to C6 with total removal of hematoma.
      CONCLUSION: The spinal epidural hematoma rarely is a surgical emergency. The
      patient presented with Brown-Sequard and Horner's syndromes. Magnetic resonance
      imaging made a rapid and correct diagnosis. The patient received an emergent
      right hemilaminectomy from C2 to C6 with removal of hematoma and subsequently
      made a complete recovery.

PMID- 7716633
TI  - Scoliosis and fibrous dysplasia of the spine.
AB  - STUDY DESIGN: This report is an account of three patients with scoliosis and
      polyostotic fibrous dysplasia involving the spine. The perioperative course of
      two patients who underwent posterior spinal arthrodesis is described. OBJECTIVES:
      The objective of the study was to show that extensive fibrous dysplasia of the
      spine and scoliosis can be treated by standard methods of posterior spinal
      arthrodesis with good results. SUMMARY OF BACKGROUND DATA: Scoliosis developed in
      three patients, and two patients underwent spinal arthrodesis. No report that
      discusses the results of this type of operation in this patient population exists
      in the literature. METHODS: Three patients with polyostotic fibrous dysplasia
      involving the spine and scoliosis were located at our institution. Two of the
      patients underwent posterior spinal arthodesis in situ; their perioperative
      courses are described. The course of the nonoperatively treated patient is noted
      briefly. RESULTS: A stable posterior spinal arthrodesis was achieved in both
      patients with no major complications. At the time of the last follow-up visit,
      both patients had radiographic evidence of a solid fusion mass with no signs of
      pseudarthrosis or graft resorption. Both patients currently are doing well.
      CONCLUSIONS: Scoliosis and its treatment has been unreported in patients with
      this condition, and this report demonstrates that satisfactory results can be
      obtained with attention to detail.

PMID- 7716634
TI  - Instrument for computerized analyses of spine motion (the CA-6000)

PMID- 7716635
TI  - [The importance of physical therapy in the treatment of Volkmann's contracture in
      children].
AB  - Over the period from 1981 to 1991 twenty-eight children were treated for
      neurovascular posttraumatic complications (Volkman's contracture), in the Centre
      for rehabilitation and physical medicine of the Children's surgical department in
      Belgrade. The success of the treatment depended on how a patient was examined for
      the first time, and how soon a proper diagnosis was established. On the basis of
      our experience we insist on an early physical treatment, i.e. while the injured
      segment is immobilized. An early kinesitherapy followed later by electrotherapy,
      parafino-therapy, vitamin B therapy and use of corrective plaster cast splints is
      the best way in treating lesions. The treatment lasted from 3 to 6 months
      depending on the seriousness of an injury. If there was no good result with
      physical therapy we carried out surgery followed by physical therapy upon the
      removal of immobilisation devices.

PMID- 7716636
TI  - [The development of ophthalmology in Serbia from the founding of the Eye Clinic
      in Belgrade on 9 July 1921 (part 2)].

PMID- 7716637
TI  - [Importance of immunomorphometric evaluation of the size and number of
      megakaryocytes in normal and pathologic bone marrow].
AB  - The aim of the present study was to evaluate the significance of
      immunomorphometric assessment of megakaryocyte size and number in normal and
      pathologic human bone marrow. Thus, we compared morphometric characteristics of
      megakaryocytes in 56 bone marrow trephine biopsies stained by immunohistochemical
      and conventional techniques. Morphometric results showed that precise
      megakaryocyte size in normal and pathologic samples can be calculated even by
      using conventional staining technique, but only employing specific stereological
      corrections. Immunomorphometric evaluation revealed populations of "small"
      megakaryocytes (< 14 microns), "morphologically unrecognized" by conventional
      staining technique (promegakaryoblasts in normal and stimulated as well as
      micromegakaryocytes in pathologic bone marrow). In patients with normal and
      stimulated megakaryocytopoises percentage of "small" megakaryocytes was generally
      low (10.6% and 14%, respect.); so, megakaryocyte number was similar in
      immunohistochemically and conventionally stained sections. In contrast,
      percentages of "small" megakaryocytes were significantly higher in patients with
      stem cell disorders (namely, myelodisplastic syndrome and chronic granulocytic
      leukaemia), as compared to controls (35.3% in MDS; 22.9% in CML and 10.6% in
      controls). In those patients megakaryocyte numbers were more sensitively detected
      by immunohistochemistry than by conventional staining.

PMID- 7716638
TI  - [The course and outcome of pregnancy in pregnant women with hypothyroidism].
AB  - The report presents the analysis of 56 pregnant women with hypothyroidism as a
      consequence of different aetiopathogenetic factor, and 20 healthy pregnant women
      with normal pregnancies and term deliveries. Patients with hypothyroidism
      diagnosed prior pregnancy (46) were treated before and during pregnancy with
      thyroid hormone preparations. Patients with hypothyroidism verified in
      subclinical form during pregnancy (10) were not treated. In all examined pregnant
      women the mean values with standard deviations for thyroid-stimulating form
      hormone levels, total thyroxine and triiodothyronine, in each trimester of
      pregnancy, free thyroxine and triiodothyronine in the first and the last
      trimester were recorded; dynamics of their trends, as well as correlation of
      values in healthy pregnant women were presented. The analysis of the pregnancy
      course revealed a significantly higher incidence of gestational diabetes mellitus
      and preeclampsia (p < 0.001). It may be suggested that hypothyroidism is one of
      the risk factors for development of gestational diabetes, and also one of the pre
      existing factors for development of preeclampsia. Delivery occurred in 83.9% of
      patients; in 12.8% of patients delivery was prior to term while spontaneous
      abortion occurred in 16.1% of cases (in one third in the first trimester).
      Similar results were observed in pregnant women with subclinical hypothyroidism.
      There were 4.2% of stillbirths which corresponded to the rate of perinatal
      mortality. One infant was born with hydrocephalus and the others were healthy. In
      the authors' opinion it is necessary to achieve normal metabolic state before
      pregnancy which should be maintained with substitutional therapy during the whole
      pregnancy.

PMID- 7716639
TI  - [Longitudinal density of the vascular network of the human thalamus].
AB  - The longitudinal density of the vascular net in twenty human thalamuses was
      measured. In all cases the lumen of the arterial branches of the posterior
      communicating artery and the posterior cerebral artery were measured, and in six
      cases the lumen of the branches of the anterior choroidal artery. The average
      longitudinal density of the examined arterial branches in the thalamic vascular
      net was 5.550 +/- 0.170 mm2. The morphologic analysis of the frontal thalamic
      section revealed highly anisotropic thalamic blood vessels.

PMID- 7716640
TI  - [Prolactin secretion in hyperthyroid individuals].
AB  - Several endocrine and metabolic changes occur in hyperthyroidism, among which
      also changes in prolactin secretion are present. Causes are numerous. However, a
      decreased content of prolactin in secretory granules of the lactotrophic cells in
      the adeno-hypophysis gland, e.i. a decreased prolactin pool, should be especially
      emphasized. Prolactin secretion of the adeno-hypophysis gland was examined in 30
      hyperthyroid patients. Normoprolacinaemia was diagnosed in basal conditions, but
      prolactin response was not so great during stimulation tests (test with
      thyrotropic hormone and eglonylic test) and suppression tests (L-DOPA and bromo
      cryptic test). This finding suggests the existence of a decreased prolactin pool
      in hyperthyroidism.

PMID- 7716641
TI  - [Immunohistochemical analysis of malignant tumors of the thyroid gland using 6
      relevant markers].
AB  - The results of immunohistochemical study of malignant thyroid tumours using six
      markers-thyroglobulin (TGB), keratin, carcinoembryonic antigen (CEA), epithelial
      membrane antigen (EMA), calcitonin and leucocyte common antigen (LCA)-are
      presented. Thirty-three cases of thyroid carcinomas were studied: 11 papillary, 8
      follicular, 7 medullary and 7 anaplastic carcinomas. All cases of papillary and
      follicular tumours showed positive reaction with TGB and 4 papillary and 3
      follicular carcinomas reacted with CEA also. 100% reactivity with calcitonin and
      CEA were observed in the medullary carcinoma group, while anaplastic carcinomas
      revealed TGB (one case), CEA (two) and EMA (three) reactivity. None of the
      studied tumours responded to LCA. TGB and calcitonin proved to be useful in
      distinguishing tumours originating in follicular cells from those originating in
      parafollicular cells and, along with LCA, enabled discrimination of anaplastic
      carcinomas from medullary carcinomas and malignant lymphomas. CEA can be only
      used as an auxiliary marker in cases of medullary carcinoma, while EMA and high
      molecular weight keratins did not prove to be reliable markers for analysis of
      malignant thyroid tumours.

PMID- 7716642
TI  - [Spontaneous intracranial hemorrhage in term neonates and infants].
AB  - Twenty nine full term haemophiliac neonates and babies, aged eight months with
      acute intracerebral haemorrhage are reported: four babies with haemophiliac
      status, one with intracerebellar bleeding due to microvascular malformation, and
      24 babies in whom the cause of bleeding could not be established (probably
      vitamin-K deficiency). Fourteen surgeries were performed in ten babies. When
      dramatic neurological signs of spontaneous cerebral stroke develop in a term
      newborn or a baby they require immediate ultrasonographic examination. This
      noninvasive method can be repeated without risk to disclose all changes into the
      bleeding focus before and after surgical treatment. Selective cerebral
      angiography was exceptionally recommended for detection of suspected vascular
      malformation. Lumbar puncture was performed in more than one third of patients to
      confirm subarachnoid bleeding. However, this method has not been accepted being
      the purposeless and risky. Pharmacotherapy should be quickly used to correct the
      supposed vitamin-K deficiency and for replacement of relevant missing plasma
      factor of the prothrombin complex. To stop bleeding and to secure surgery the
      replacement substitute must raise the factors' level at least by 50 percent. The
      treatment of choice is vitamin-K1, 1-3 mg and fresh frozen plasma 10ml/kg of body
      weight. The neurological recovery was in general satisfactory after the
      stabilization of acute clotting disorder was achieved. Eight babies died (28
      percent), five of them were admitted in deep comatose state.

PMID- 7716643
TI  - [Occurrence of bacterial infection and sensitivity of their causative agents to
      antibiotic drugs in patients with acute leukemias].
AB  - The paper summarizes the results of the study of bacterial infections, occurring
      in neutropenic patients with acute leukaemia treated at the Radivoje Berovic
      Intensive care unit of the Institute of Haematology, University Clinical Centre,
      Belgrade. The majority of infectious episodes, as well as most bacteriaemias,
      were caused by Gram-positive bacteria keeping rapid increase of Gram-positive
      bacteriaemias in neutropenic patients. Our results suggest that in studied
      hospital conditions, amikacin should replace gentamicin as empiric antibiotic
      therapy (in addition to a beta-lactam antibiotic). In non-responding patients
      addition of an anti-staphylococcal agent should be considered.

PMID- 7716644
TI  - [Methods of study of the effects of modern administration (management) on the
      autonomy and satisfaction of physicians in clinical practice].
AB  - Marketing principles in health care delivery systems, reducing financial funds
      for health institutions and permanently increasing costs of medical equipment are
      responsible for the growing influence of management on physician's autonomy and
      working satisfaction. A questionnaire research was carried out in order to
      determine the best method of examination of this influence in Belgrade. All
      tested persons were medical doctors working in a primary health centers for 7
      hours per day, who examined about 26 patients every day. More than a half of
      physician improved their knowledge by reading professional publications 6 hours
      per week. In spite of the fact that they all worked in the same institution, they
      expressed different opinions regarding the organisation. In the physicians'
      opinion clinical freedom and working satisfaction were at the high level, and
      partly connected with management practice. At the same time they were very
      unsatisfactory with personal income and budgetary distribution in the
      institution. It is evident that the method described in this article is useful in
      the analysis of the present situation related to management and physician's
      practice in the country.

PMID- 7716645
TI  - [Changes in sensitivity to penicillin and an increase in virulence in beta
      hemolytic streptococci followed by changes in the clinical picture of
      streptococcal syndrome].
AB  - According to reports from different geographic areas, the last decade has been
      characterised with an increasing number of streptococcal diseases. The new
      streptococcal "pathomorphosis" is presented by alteration of adhesive properties
      and distribution of various serotypes (domination of M1 and M18 serotypes). It is
      also expressed by an increased production of pyrogenic exotoxin and necrotic
      factor. As a consequence, apart from increasing incidence of streptococcal
      infections, it is observed that the streptococcal syndrome has often grave
      prognosis followed with a high percentage of mortality. Also a new clinical
      entity is also described; that of Toxic Shock Like Syndrome. The results of
      investigation concerning the susceptibility of beta-haemolytic streptococci to
      penicillin are encouraging. Penicillin resistant strains are not discovered among
      clinical isolates so far. However, the increased percentage of penicillin
      tolerant strains, and possibility of induction of penicillin resistance, can be
      considered as a serious warning. For that reason, further investigation of the
      mechanisms of developing penicillin tolerance and resistance appears to be highly
      recommended.

PMID- 7716646
TI  - [Atrium natriuretic peptide in kidney diseases].
AB  - The aim of this review is to summarize current knowledge about atrial natriuretic
      peptide--its role in pathophysiology of renal disease. Presumed role of atrial
      natriuretic peptide (ANP) in renal pathophysiology is based on the study of blood
      levels and renal effects of ANP in the presence of different manipulations
      (variations in dietary sodium intake, posture, water immersion or infusion of
      synthetic ANP) in patients with different renal diseases. In most of nephrotic
      patients ANP increases diuresis and natriuresis. However, small to great
      difference in natriuretic response was found in comparing with healty volunteers.
      Increased release of ANP in humans with chronic renal insufficiency would be
      expected as consequence of volume overload, diminished glomerular filtration rate
      and hypertension. Elevated plasma concentrations of ANP in end-stage renal
      disease are restored to normal level by successful renal transplantation,
      indicating that renal function is determinant of plasma ANP concentration.
      Fluctuations in plasma ANP-level during acute renal failure are related to blood
      volume changes in these patients.

PMID- 7716647
TI  - [Endothelins].
AB  - Based on the data from current literature a survey of the new endothelial cell
      derived peptides endothelins and their characteristics are given. Having the most
      and longest vasoconstrictor activity that has been described to date and ability
      to stimulate the release aldosterone, catecholamine and renin, endothelin-1
      became the subject of many studies on its pathogenetic role in arterial
      hypertension. The data also indicate that endothelin may be one of important
      deleterious mediators in the pathogenesis of ischemic acute renal failure due to
      its predominant preglomerular vasoconstrictor activity and ability to induce
      mesangial cells contraction. In addition to its vasoactive properties, endothelin
      has a mitogenetic and natriuretic effect. The demonstration that mesangial cells
      release endothelin into culture medium together with the finding that its gene
      expression and production in mesangial cells are regulated by glomerular
      inflammatory reaction factors may suggest that endothelin also participates in
      the complex process of glomerular disease progression. Therefore, it is a very
      interesting vasoactive peptide, with more actions beyond the regulation of
      cardiovascular tone, which suggest the widespread distribution of its high
      activity binding sites in blood vessels, brain, lungs, kidney, adrenal glands,
      spleen and intestines.

PMID- 7716648
TI  - [The erythrocyte sedimentation test (part 1)].

PMID- 7716650
TI  - [Color doppler mapping in the diagnosis of prostatic carcinoma].
AB  - The authors examined 70 patients with histologically confirmed prostate carcinoma
      in different stages by transrectal ultrasonography in the B mode and by
      ultrasonography by colour flow mapping and pulsed Doppler. They investigated the
      distribution of the blood supply, resistance index (RI) and pulsatility index
      (PI). It did not prove possible to find an association between the blood supply
      and stage T nor with grading G. A certain relationship was observed between the
      blood supply and the progression of the tumour. In newly detected growing tumours
      and in progressing tumours not responding to treatment the blood supply was more
      ample. On the other hand, in all stationary tumours reacting well to treatment
      the blood supply was reduced.

PMID- 7716649
TI  - [Acute intermittent porphyria].
AB  - Acute intermittent porphyria is an inherited disease caused by genetic deficiency
      of enzyme prophobilinogen deaminase, which stopped heme synthesis. It is
      characterized by overproduction, accumulation and excretion of heme precursors.
      The authors present a young woman with clinical signs and symptoms of disease,
      treated successfully with heme-arginate, a newly synthetized drug in clinical use
      since 1985.

PMID- 7716651
TI  - [Adrenal gland hemorrhage in adulthood].
AB  - The author presents five case-histories of haemorrhage into the adrenal in adult
      age. He emphasizes specially the difficulty of preoperative diagnosis.

PMID- 7716652
TI  - [Rectosigmoid reservoirs (pouch)].
AB  - A low pressure and high capacity rectosigmoid reservoir for urine is formed
      without the need for colostomy, augmentation or extensive bowel surgery.
      Reservoir is created by antimesenterial detubularization of the rectosigmoid and
      subsequent suturing. The authors describe the operation technique and analyses
      the results in 20 patients who were followed up 1-25 (average 14) months after
      operation. All patients are continent during the day time and at night. Two
      patients had at the sites of implantation ureteral stricture, which in one
      necessitated reoperation and undiversion and in the other endoscopic dilation of
      the stricture.

PMID- 7716653
TI  - [Personal experience in treatment of urolithiasis using the MEDILIT M6
      extracorporeal lithotriptor].
AB  - The authors report on their experience with the destruction of kidney stones with
      the lithotriptor MEDELIT M6 of Medipo Co. BRNO on the development of which they
      participated. They checked 878 patients where the instrument was used and where
      the condition of a half-year interval after the operation had been met. In these
      patients 119 operations were made 87% of which were successful. No serious
      complications occurred; after operation they observed in 17% of the patients
      complications ensuing from a block of the ureter by the passing stones. The
      extracorporeal lithotriptor MEDELIT M6 is a reliable instrument with a low rate
      of defects and cheap operation which makes accurate X-ray and sonographic
      focusing on the stone possible as well as adequate disintegration of the
      concrement without damaging surrounding tissues. It is comparable with
      instruments of the same generation manufactured abroad.

PMID- 7716655
TI  - [Personal experience with uretero-renoscopy].
AB  - The authors submit evaluation of 188 patients operated on during five years (1989
      1993). Using the ureterorenoscopic technique (URS), 207 operations have been
      performed. The average age in the group of patients was 56.1 years. In general
      anesthesia 151 operations were completed, in spinal anesthesia 54, in
      neuroleptanalgesia 1 and without any anesthesia 1. The postoperative ureteric
      intubation was accomplished 128 times (61.8%). The moderate dilatation of the
      hollow system of the kidney was proved ultrasonographically in only 7 cases. The
      average postoperative hospitalization reached 5.8 days. Out of 207 operations, we
      have reached successful result 177 times (85.5%) and 30 times (14.5%) we were not
      able to accomplish the operation only by means of the URS. 184 operations were
      performed because of urolithiasis (88.9%) and 23 (11.1%) for other reasons. Out
      of 184 URS for urolithiasis, 156 (84.8%) were successful and there was no
      difference found between pelvic (85.4%) and lumbal (83.6%) localization of
      urolithiasis in the view of success rate. The authors summarize the causes of
      mishaps and following solutions. The biochemical analyses of 153 concrements are
      added.

PMID- 7716654
TI  - [Percutaneous nephrolithotomy].
AB  - Within eight years, since October 1985 till June 1993, we had been operating on
      409 patients, who had been subjected to 500 percutaneous nephrolithotomies. In
      30% per cent of all the operations we had used mechanical, electrohydraulic or
      ultrasound lithotripsy. Out of the total number of the patients, 7 per cent had
      been discharged with the residual stones, but in 5.6 per cent the ESWL or
      spontaneous exodus had been presumed. Serious complications we had registered at
      10 patients (e.g. 2 per cent of all operations). None of them however had
      required an emergency nephrectomy. The authors discuss the today's position of
      the PNL among the other operative methods of treatment of urolithiasis.

PMID- 7716656
TI  - [Transvaginal urethrovesicopexy].
AB  - The authors present their own modification of Stamey's operation of female stress
      incontinence. Using a two-needle applicator of their own design, they introduce
      by transvaginal punction fibres next to the cervix of the bladder into the
      epigastrium. By tightening the fibres they elevate the cervix of the bladder. The
      elevation is checked by endoscopy. Using this method they operated 25 women. They
      did not observe any serious complications of the operation. Previous operations
      in the pelvis minor did not affect the duration of the operation.

PMID- 7716657
TI  - [Doppler ultrasonography in successful varicocele surgery].
AB  - The authors examined 47 patients after operation on account of varicocele by
      colour flow mapping and Doppler frequency analysis. In addition they evaluated
      the postoperative finding clinically and examined also the spermiogram. The
      greatest success of surgical treatment was observed after laparoscopic ligature
      of the v. spermatica--a success rate of 91% was recorded after this operation.
      Bernardi's operation was successful in 62%, Paloma's in 56% of the patients. From
      18 patients with a pathological spermiogram before operation they observed
      improvement in 25%.

PMID- 7716658
TI  - [Surgical activities at urologic departments in Slovakia 1990-1993].
AB  - In 1990 "The classification of urological operations" was introduced to all
      urological departments in Slovakia. The aim of the classification was to evaluate
      the quality of work of individual departments in respect of recent trends in
      surgical therapy. The annual analysis shows the procedures, which are necessary
      to be replaced by modern ones. The review of the first four-years shows the
      increase in number of operations almost by one third. Twenty of most common
      operations represent 73.4% of all urological procedures. The most frequent
      operation is prostatectomy accounting 11.8% of all operations. During the follow
      up period the therapy of urolithiasis has changed principally. The results of
      surgical activity analysis support the need to extend methods of urinary
      diversion using intestine and to increase the number of radical cystectomies and
      prostatectomies.

PMID- 7716659
TI  - [Generalized melanoblastoma of the lower urinary tract].
AB  - The primary metastatic melanoblastoma presented with macroscopic haematuria as a
      first sign is described. So far it is our first experience with such a type of
      tumor in lower urinary tract in ageing man. The references in literature are
      scarce on this subject.

PMID- 7716660
TI  - [Long-term results of therapy in patients with retroperitoneal fibrosis].
AB  - In 1972-1991 at the urological clinic in Hradec Kralove 13 patients with
      retroperitoneal fibrosis were treated. In six idiopathic fibrosis, primary
      fibrosis (morbus Ormond) was involved. By surgery only one patient with the
      primary disease was treated, five patients with secondary fibrosis only
      conservatively (by nephrostomy, by introduction of an ureteral endoprosthesis and
      prednisone administration 1200-1500 mg in total). Seven patients, incl. five with
      primary fibrosis, had combined treatment, an open operation with subsequent
      administration of prednisone. All remained under dispensary care of the clinic.
      During check-up examinations renal function and congestion in the urinary
      pathways was examined. In morbus Ormond treatment was successful in 83% of the
      patients (one patient died from myocardial infarction on the fifth day after
      operation); in patients with the secondary disease treatment was successful in
      60%.

PMID- 7716661
TI  - [Urologic complications in sacrococcygeal agenesis].
AB  - In 11 children with partial sacrococcygeal agenesis without concurrent patent
      cystic myelomeningocele clinical symptoms were analyzed as well as the character
      of dysfunction of the bladder and therapeutic results. The cause of urinary
      incontinence, which was a constant symptom, was not diagnosed correctly in six
      children. Due to impaired innervation, mostly of the supranuclear type, the
      bladder dysfunction had more frequently the character of impaired evacuation (8
      children) always with obstruction of the flow at the level of the external
      sphincter. Areflexia of the detrusor was found in three children. In this group
      changes of the upper urinary pathways were found in four children (three times
      unilateral reflux, twice dilated ureters, twice also pyelonephritis), always in
      conjunction with a bladder of low compliance. The impaired storage of urine found
      in three children was due to hyperreflexia of the bladder. After surgery (three
      children), conservative treatment (8 children) and their combination progression
      of changes of the upper urinary pathways was arrested and the degree of
      incontinence improved or was completed relieved during the 18-78-month follow-up
      of all patients. Extirpation of the associated subcutaneous lipomyelomeningocele
      and release of the attached spinal cord in three children aged 5, 10 and 12 years
      did not lead to improvement of the nervous lesion in any of the patients.

PMID- 7716662
TI  - [Prophylaxis with ciprofloxacin in transurethral surgery].
AB  - The purpose of the study was to compare in a prospective randomized study the
      effect of three doses of prophylactic administration of ciprofloxacin in 25
      patients and a control group of 26 patients without prophylactic antibiotic
      treatment in conjunction with transurethral surgery. In the group of patients
      with prophylaxis there is a significantly lower incidence of clinical
      manifestations of infection, as compared with the group of patients without
      prophylaxis which reduces the necessity to administer antibacterial drugs during
      the postoperative period.

PMID- 7716663
TI  - [Continent enterocystoplasty in urinary bladder exstrophy].
AB  - During the last two years from 1992 to February 1994 5 patients (2 girls and 3
      boys with median age 7 years) underwent construction of continent large-capacity
      low pressure reservoir for failed bladder exstrophy reconstruction. Small bladder
      with inadequate capacity, decreased detrusor compliance and urinary incontinence
      were the indication for enterocystoplasty. The pouches were reconstructed from
      detubularized, reconfigured bowel using incorporated bladder remnant. Bowel
      segments included ileocecum in 4 patients and ascendig colon in one.
      Reconstruction of the vesical neck was accomplished by the Young-Dees-Leadbetter
      procedure in 4 patients. Two children underwent reimplantation of ureters into
      the bladder and three ureters of two patients were reimplanted by the Goodwin
      technique into the colon. The Mitrofanoff continence mechanism using appendix was
      applied in 3 patients. Preoperation bladder capacities were 12 up to 100 mL and
      after enterocystoplasties improved to mean 300 mL and maximum 550 mL. Four
      patients are in complete urinary retention and are managed by clean intermittent
      catheterisation every 3 to 4 hours. One patient voids spontaneously with little
      residual urine by abdominal straining and pelvic muscle relaxation alone. Short
      term follow-up (3 months to 2 years) showed stable renal function in all
      patients. In 2 patients with preoperative hydronephrosis caliectasis decreased.
      This series supports the efficacy of continent enterocystoplasty as an
      alternative procedure to previous forms of urinary diversion in the management of
      failed exstrophy reconstruction.

PMID- 7716664
TI  - [Infections in neutropenic patients].

PMID- 7716665
TI  - [Viral infections in the leukemic patient].

PMID- 7716666
TI  - [Fungal infections in neutropenic patients].

PMID- 7716668
TI  - [Infection in the granulocytopenic patient with acute leukemia].

PMID- 7716667
TI  - [Infective complications in bone marrow transplantation].

PMID- 7716669
TI  - [Hemoglobin and blood donation: an old concept that is always new].

PMID- 7716671
TI  - [Hereditary spherocytosis: clinical characteristics and treatment with
      splenectomy].
AB  - PURPOSE: To analyse the clinico-biological characteristics at diagnosis, the
      clinical course, and the response to splenectomy of a series of patients with
      hereditary spherocytosis (HS). PATIENTS AND METHODS: The clinical records of 61
      patients diagnosed of HS along 30 years were reviewed. The diagnosis was based
      upon the existence of family history, physical findings, blood cell examination,
      reticulocyte count, peripheral blood spherocytes, red-cell osmotic fragility,
      auto-haemolysis, serum haptoglobin, LDH, non-conjugated bilirubin and direct anti
      human globulin test. Data regarding the time of diagnosis and clinical course
      were taken into account in every case. Within the sub-group of 29 patients
      undergoing splenectomy, the changes in haemoglobin rates and reticulocyte and
      platelet counts after surgery were evaluated. RESULTS: Of the 61 patients, 35
      were men and 26 women; the median age at diagnosis was 13 years (range: 0-64
      years). Family history was positive in only 40% of the cases. The mean
      haemoglobin rate was 112 g/L (range: 46-151 g/L), over 60% of the patients having
      anaemia. The mean reticulocyte count was 282 x 10(9)/L (range: 31-583 x 10(9)/L),
      this being above 100 x 10(9)/L in 91% of the cases. Red-cell osmotic fragility
      with fresh blood was increased in 86% of the cases, and in 97% after blood
      incubation. Serum haptoglobins were decreased, whereas LDH was increased in 58%
      of the patients and non-conjugated bilirubin in 72%. Splenomegaly appeared in the
      clinical course in 87% of the patients; cholelithiasis was present in 31.5% of
      them. Haemoiytic crises were seen in 45% of patients, aplastic phases in 7%, and
      transfusion was needed by 16% of the patients to variable extents. Splenectomy
      was performed in 50% of the instances before 14 years of age (range: 4-64 years),
      and it increased haemoglobin rates in 40 g/L, anaemia being corrected in all
      cases; the mean reticulocyte count returned to normal, but thrombocytosis
      developed after surgery, it being present in 82% of the cases 2-3 months later.
      CONCLUSIONS: (1) Wide clinical variability is seen in HS, from severe forms
      requiring frequent transfusion to asymptomatic cases. (2) Highly frequent
      findings in HS are reticulocytosis and splenomegaly; relatively frequent were
      anaemia, haemolytic crisis and cholelithiasis, in this order. (3) Anaemia was
      always corrected after splenectomy, which also rose the haemoglobin rate even in
      the cases without anaemia, and returned the reticulocyte count to normal values.

PMID- 7716670
TI  - [Hemoglobin in blood donor selection].
AB  - PURPOSE: To evaluate and establish a relationship between serum ferritin value
      and haemoglobin level, serum iron or transferrin in volunteer blood donors.
      MATERIAL AND METHODS: We have studied a group of 479 blood donors from Navarra's
      Health Area V, whose blood cell examination, iron, ferritin and transferrin
      values were determined. We classified these donors in 4 groups according to their
      ferritin concentration (ng/mL): f1 (0-12), f2 (13-20), f3 (21-400) and f4 (more
      than 400). The results were analyzed by the statistical program SPSS/PC+. The
      sensitivity, specificity, accuracy and predictive value of the positive test, for
      the determination of haemoglobin level as an indicator of iron deposits were
      calculated. RESULTS: The comparative statistical study of all these groups
      indicated that there were significant differences in the ferritin and the
      haemoglobin values (p < 0.001 and p < 0.05, respectively), except between f1 and
      f2, which only presented and intergroup difference in the ferritin values. In
      blood donors, the estimation of iron deposits from the hemoglobin level showed a
      diagnostic sensitivity greater than 90%. CONCLUSIONS: Haemoglobin values would
      allow the selection of those donors that could have an iron deficiency, or a
      borderline concentration; nevertheless, it would not allow the distinction
      between these two groups. This last observation is not important because donors
      that show a ferritin value lower than 20 ng/mL should not give blood. When the
      ferritin is greater than 20 ng/mL in men, the iron deposits will be adequate in
      97% of them. This percentage is about 90 in women whose haemoglobin level is
      greater than 12.5 g/dL. Therefore, we consider that haemoglobin values present a
      good cost/benefit ratio for donor selection.

PMID- 7716672
TI  - Immunophenotypic characteristics of acute leukaemia after myelodysplastic
      syndromes.
AB  - PURPOSE: To analyse the immunophenotype of acute leukaemia (AL) after
      myelodysplastic syndromes (MDS) (MDS-AL) and to compare the immunophenotypic
      profile of acute myeloblastic leukaemia (AML) secondary to MDS (MDS-AML) with
      that of "de novo"-AML. PATIENTS AND METHODS: Twenty patients with MDS-AL and 29
      patients with "de novo"-AML were studied. Morphocytochemical and flow cytometric
      studies were done in each case. RESULTS: All the MDS-AL studied displayed a
      myeloid phenotype (MDS-AML). The main difference between MDS-AML and "de novo"
      AML was a significantly higher frequency of CD34 expression in the first group.
      Differences concerning the expression of other non-lineage related or myeloid
      associated markers were not statistically significant, although the percentage of
      cases CD15(+) was lower in MDS-AML. The overall frequency of expression of
      lymphoid-associated markers was similar in both groups, T-cell markers being more
      frequently detected. CONCLUSIONS: Our findings support the usefulness of
      immunophenotyping studies to characterize MDS-AL and suggest some
      immunophenotyping differences between MDS-AML and "de novo"-AML which might have
      biological and prognostic significance.

PMID- 7716673
TI  - [Characteristics of patients with low grade malignant lymphoma and long
      survival].
AB  - PURPOSE: To analyse the initial and evolutive characteristics of the patients
      with low-grade lymphoma and long survival (> or = 12 years). MATERIAL AND
      METHODS: The initial data (clinical, laboratory, histologic type, stage) and the
      clinical course (response to therapy, response duration) of 52 patients with low
      grade lymphoma diagnosed before 1980 were analysed. The statistical study was
      carried out by means of the chi-square test with Yates' correction and Student's
      t; the actuarial survival was estimated, and the duration of remission was
      assessed by the Kaplan and Meier method. Curves were compared by the log rank
      method. RESULTS: The 12-year survival as a whole was 32% (CI: 95%: 18.5%-45.5%).
      Of the 52 patients, 13 (25%) survived over 12 years. Nine were men and 4 women,
      with median age of 41 years (range: 22-68 years). Three cases had lymphocytic
      lymphoma and 10 had follicular lymphoma; 2 were in stage I-II and 11 in stage III
      IV. Those patients who would become long-survivors had at diagnosis lesser
      frequency of spread lymph-node regional involvement (> or = 3 sites): 46% vs
      81.8%, p = 0.04, as well as lesser percentage of bone-marrow involvement (38.4%
      vs 78.1%, p = 0.023). They were also better responders to treatment (CR+PR = 100%
      vs 71%, p = 0.013) and with longer duration (actuarial median duration of
      response 8 years vs 1.5 years, p = 0.005). CONCLUSIONS: According to the present
      analysis, low-grade lymphoma patients who have at diagnosis low tumoral
      involvement (not too extensive lymph-node involvement, disease-free bone-marrow)
      and show good response to treatment have a better prognosis and may hope for a
      longer survival.

PMID- 7716674
TI  - [Inhibitor of the extrinsic pathway of coagulation and cytokines in patients with
      sepsis].
AB  - PURPOSE: To analyse the possible correlation between the plasma levels of the
      extrinsic pathway inhibitor (TFPI) in patients with infection along with two
      cytokines mediating in the action of bacterial endotoxin on the vascular
      endothelium, namely, tumour factor (TNF) and interleukin-1 (IL-1). PATIENTS AND
      METHODS: Twenty-five patients with infection, none of them showing septic shock
      or disseminated intravascular coagulation, were studied. Plasma TFPI
      concentration was assessed by a chromogenic substrate technique; TNF was
      determined with immunoradiometric methods and IL-1 was estimated with ELISA. The
      results were compared with those of a group of 25 healthy subjects matched for
      age and sex. RESULTS: Positive blood cultures were found in 15 of the 25 patients
      (60%), 12 due to gram-negative and 3 to gram-positive germs. A significant
      increase of TFPI (p < 0.004), TNF and IL-1 (p < 0.001) was found in infection
      patients with respect to the control subjects. No significant correlation between
      TFPI and TNF or IL-1 was found. CONCLUSION: Increased TFPI, unrelated to
      cytokines, is present in patients with sepsis.

PMID- 7716675
TI  - [Monocytoid B-cell lymphoma: clinico-pathologic study of 2 cases].
AB  - Monocytoid B-cell lymphoma, considered as a low-grade lymphoma, is seen most
      frequently in persons of advanced age, chiefly women. It is often diagnosed in
      lymph-node phase, in low stages (I-II), and peripheral blood, bone-marrow or
      spleen are seldom involved. The morphologic and immunohistochemical study of two
      patients with monocytoid B-cell lymphoma is presented. The characteristic cell
      morphology, with homogeneous nuclei, low number of mitoses, and clear, wide
      cytoplasm, was present in both. Tumour cells expressed CD45, CD20, HLA-DR and
      monoclonal IgM-lambda and lambda chains, respectively. Case no. 1 had more
      irregular nuclei, protruding nucleoli, advanced stage at diagnosis and shorter
      clinical course. An epithelioid granulomatous reaction was present in case no. 2,
      which delayed the diagnosis until relapse. The diverse forms of clinical onset of
      monocytoid B-cell lymphoma, as well as its possibly aggressive course,
      association with other types of lymphoma and the difficulties for an adequate
      morphologic identification are commented.

PMID- 7716676
TI  - [Rearrangement of the alpha RAR and pml genes in promyelocytic leukemia].
AB  - The purpose of this work was to assess the re-arrangement of RAR-alpha and pml
      genes in a group of patients with acute promyelocytic leukaemia (APL) in
      different stages of the disease. Twenty-two patients with APL were studied. Of
      them, 17 were at the onset and 5 had achieved already complete haematological
      remission (CR). Evolutive post-remission studies were performed in 8 cases. The
      cytogenetic analysis was carried out at diagnosis by means of the G-band
      technique in 14 patients. The molecular study of RAR-alpha and pml genes was made
      with the Southern method. The common anomaly, t(15;17) was present in 7 of the 9
      cases with evaluable metaphases (78%), in one case a 17q+ was the only
      cytogenetic alteration and another patient had normal karyotype. The molecular
      study showed re-arrangement of one or both genes involved in the translocation in
      the 17 patients studied at the onset of the APL. Those patients studied only in
      CR showed a germinal configuration. Rearrangement bands reappeared in 3 of the 8
      patients evaluated along their clinical course. These results are in concordance
      with previous studies, in which re-arrangement of RAR-alpha and pml genes had
      been found in APL, despite there are instances in which no cytogenetic anomalies
      are found; this confirms the interest of molecular studies in the diagnosis and
      follow-up of APL patients.

PMID- 7716677
TI  - [The PETHEMA LAL/89 protocol].

PMID- 7716678
TI  - [Cardiotoxicity and intensification chemotherapy].

PMID- 7716679
TI  - [Persistent monocytosis associated with chronic lymphatic leukemia].

PMID- 7716681
TI  - [Cryopreservation, preservation at 4 degrees and cost reduction in
      autotransplantation of hematopoietic precursor cells].

PMID- 7716682
TI  - [Too many "normal karyotypes" in the transported samples].

PMID- 7716680
TI  - [Oral anticoagulation].

PMID- 7716683
TI  - New findings in psychiatric genetics: implications for social work practice.
AB  - Advances in psychiatric and behavioral genetic research have expanded the
      knowledge base about the genetic etiology for many psychiatric disorders,
      transforming the practice of psychiatry. The opportunity exists to develop a well
      defined role for social workers in dealing with psychiatric genetic issues. This
      article outlines roles for social work in psychiatric genetics, reviews the
      literature which explains the genetic component of the most common psychiatric
      disorders, and considers the clinical implications that arise in social work
      practice with clients dealing with psychiatric genetic issues.

PMID- 7716684
TI  - Social work role in a case of withdrawal of basic life supports.
AB  - This paper is about the problems faced by a responsible family in making a
      decision about the maintenance of nutrition and hydration for a member who had
      not yet prepared a Living Will or Health Care Proxy form. We believe it to be of
      value to other health care workers facing similar problems. This report covers
      the impact on staff, and the work with patient's family, and the stress of
      interdisciplinary collaboration on both professional and administrative staff.

PMID- 7716685
TI  - Assessing the responsiveness of health services to ethnic minorities of color.
AB  - Ethnic minorities of color are disadvantaged on most indicators of health and
      wellness, yet, health services have not been adequately responsive to this
      group's needs. This paper explores the improvement of health services for this
      population by discussing common criteria for the assessment of responsiveness:
      availability, accessibility, and acceptability. Illustrative examples drawn from
      different ethnic minority groups will be utilized in the discussion of assessment
      criteria and ideas for cultural responsiveness highlighted.

PMID- 7716686
TI  - Social work treatment with children, adolescents, and families exposed to
      religious and satanic cults.

PMID- 7716687
TI  - Helping home bound elderly clients understand and use advance directives.
AB  - The Patient Self-Determination Act passed by the United States Congress in
      December 1991 is usually defined in terms of the responsibility of health care
      institutions to inform patients about their rights and privileges in connection
      with life support measures. Social workers as well as other providers are aware
      that the time of admission is neither the auspicious time nor is the hospital the
      place of choice for conveying that information. The intent will be better
      fulfilled when patients arrive at the hospital with these decisions made and the
      documents in hand. This article presents the process of presenting the options of
      living wills and health care proxies to patients who receive home care services.
      With the cooperation and support of her team, the social worker informed these
      patients about these documents in their own homes and helped them with decisions
      required. The problems encountered, how help was given, and what was learned that
      can be used by other social workers in both practice and planning are covered.

PMID- 7716689
TI  - Death review: an important component of grief resolution.
AB  - This paper discusses the concept of death review. Death review is an important
      component of grief resolution. The circumstances of the illness and death need to
      be repeated several times as survivors cope with their own pain and distress. The
      smallest event recalled may be helpful in resolving grief.

PMID- 7716688
TI  - A kidney donor's dilemma: the sibling who can donate--but doesn't.
AB  - The decision making process undertaken by a sibling who chooses not to donate a
      kidney to a brother or sister who needs a transplant is the subject of this
      article. Presented from the perspective of the potential donor client, the paper
      focuses on the moral and ethical concerns indicated when there are two equal but
      competing rights involved in the decision. It also addresses pertinent
      attitudinal dimensions and social and health issues that affect all parties--the
      client, the marital partner, the family of origin, and the patient's immediate
      family. The article concludes by addressing "what" and "how" social workers
      assist clients after the difficult decision not to donate has been made.

PMID- 7716690
TI  - A national survey of medical risk assessment instruction in general practice
      residency programs: Part III.
AB  - This is the third of a three-part series reporting a national survey of general
      practice residency directors and their evaluation of the medical risk assessment
      (MRA) instruction curriculum in their programs. The purpose of Part III was to
      report the program directors' narrative comments in response to six essay-style
      questions regarding problems, suggestions, and innovations encountered in their
      efforts. Availability of physician faculty was the most frequently mentioned
      problem in providing MRA instruction for general practice residents. Defining and
      communicating goals and objectives were also of major concern. Proposed solutions
      included attempts to recruit additional physician faculty and improved
      supervision and management of program activities, especially off-service
      rotations. There was no consensus as to what future modifications the Commission
      on Dental Accreditation should make in its approach to teaching MRA as defined in
      Standard 14. The majority of responses indicated a desire to decrease total
      experience, especially in physical examination requirements other than head and
      neck.

PMID- 7716692
TI  - Management of spontaneous osteoradionecrosis: a case report.
AB  - Spontaneous osteoradionecrosis of the mandible is an oral complication of
      radiation therapy. Bone necrosis, unrelated to trauma or infection, is more
      common when high doses of radiation, including interstitial implants, are
      delivered to a large bone volume. Management provides a challenge for the dentist
      and patient. When conservative, non-surgical treatment is unsuccessful, surgical
      debridement with adjunctive hyperbaric oxygen therapy and eventual mandibular
      resection may result. A case of spontaneous osteoradionecrosis is described which
      underscores the clinical course of the disease and treatment outcomes.

PMID- 7716693
TI  - Drug prescription practices of hospital dentists.
AB  - Surveys were sent to the membership of the American Association of Hospital
      Dentists to evaluate their prescribing practices. The 295 surveys that were
      evaluated revealed that current pharmacological interventions are directed
      primarily to the elimination of pain and infection. The respondents listed a wide
      variety of prescribed drug groups as well as numerous drugs within each drug
      group. Our respondents indicated that the future will necessitate a greater
      knowledge base in drug groups that today are not as widely used and recognized,
      such as antiviral and antifungal agents.

PMID- 7716691
TI  - Factors contributing to dentists' extraction decisions in older adults.
AB  - To evaluate which dental and non-dental factors contributed to dentists'
      extraction decisions in a sample of older adults, an archival study was conducted
      using community-dwelling and long-term-care older adults receiving dental care at
      an urban seniors' clinic. Four dentists who provided dental care to older adults
      reviewed patient records for whom they had extracted at least one tooth over a 21
      month period. They identified one or more factors contributing to their
      extraction decisions. From 105 adults (mean age, 80.6), there were 221
      extractions. Frequent contributors to dentists' extraction decisions included non
      restorability in 53.8% of all extractions, dental caries (45.6%), prosthetic
      considerations (45.2%), and periodontal disease (40.3%). The non-dental
      contributors in 13% to 17% of extractions included patient/family request,
      inability to care for one's teeth, and financial limitations. When identifying
      the "most important" (or "primary") factor in their extraction decisions,
      dentists most frequently indicated non-restorability, followed distantly by
      patient/family request, periodontal disease, and financial limitations. This
      investigation demonstrates that non-dental factors are important in dentists'
      extraction decisions. Of these, patient/family request and financial limitations
      appear to be most influential.

PMID- 7716694
TI  - Oral hygiene care levels in Iowa intermediate care facilities.
AB  - This study was undertaken to improve understanding of current oral hygiene care
      practices in intermediate care facilities. Questionnaires were sent to directors
      of nursing of all licensed intermediate care facilities in Iowa. Results show
      that an estimated 57% of residents needed direct oral hygiene assistance. In all
      intermediate care facilities, the majority of direct oral hygiene care was
      provided by aides. Oral hygiene care was often not provided at an optimal level,
      and the main reasons reported for this lack of care were uncooperative residents
      (82%), lack of perceived need by aides (68%), and inadequate time/personnel
      (49%). Development and promotion of oral hygiene care programs in intermediate
      care facilities must take into consideration the realities and problems involved.
      Otherwise, efforts to introduce or implement new or improved care programs will
      fail.

PMID- 7716696
TI  - Some things on my mind.

PMID- 7716697
TI  - A preventive dentistry training program for caretakers of persons with
      disabilities residing in community residential facilities.
AB  - People with disabilities develop more dental disease than the average population
      and have a harder time accessing and using resources for dental treatment. It is
      therefore critical to prevent dental problems in this population. This article
      discusses the development and use of a preventive dentistry training program
      consisting of a videotape, workbook, instructions for trainers, and pre- and post
      tests. The training program was designed to facilitate integration of dental and
      behavioral information into daily routines. Participants were able to demonstrate
      that they could learn the information in the training materials using the
      methodology that was employed. Further work remains to be done to revise and
      disseminate the materials and to demonstrate that the knowledge that the
      participants gained can be effectively applied in community care settings.

PMID- 7716695
TI  - Effects of medication on parotid salivary flow rates in an individual with
      dementia of the Alzheimer type.
AB  - Data available on the relationship between salivary function and specific drug
      therapy are sparse. We measured unstimulated and stimulated parotid salivary flow
      rates associated with the drug therapies. Our ancillary study design is an N = 1
      double-blind randomized controlled trial in which the patient undergoes a series
      of treatment blocks of either placebo or active treatment. The purpose of the
      parent N of 1 study was to find the "best single drug" treatment for a resistive
      patient diagnosed with dementia of the Alzheimer type. This study demonstrates
      that thiothixene was associated with inconsistent effects on parotid flow.
      Oxazepam had no effect on his parotid function, and diphenhydramine hydrochloride
      had inconsistent but generally negative effects. The data also show that this
      individual with dementia of the Alzheimer type had lower baseline unstimulated
      and stimulated parotid salivary flow rates when compared with mean "normal"
      values; however, flow rates were above the lowest 10th percentile of "normal"
      volunteers.

PMID- 7716699
TI  - Testing toothbrushing ability of elderly patients.
AB  - An individual's ability to perform adequate oral care may become jeopardized by
      medical and physical insults associated with the aging process. Declines in oral
      care abilities may be difficult to identify, and usually go unnoticed and
      unaddressed. This study examined a tool developed to assess toothbrushing ability
      in elderly patients. The Toothbrushing Ability Test (TAT) was examined for its
      ability to predict brushing effectiveness (measured by plaque levels) and to
      determine its interrater and intrarater reliability. Fifty-eight dentate
      subjects, age 65 and older, from the Portland Veterans Affairs Medical Center and
      a community nursing home participated. Results showed highly significant Spearman
      correlations between TAT scores and plaque levels (r = 0.719; p < 0.000).
      Correlations also revealed high interrater (r = 0.87) and intrarater reliability
      (r = 0.82). The results suggest that the TAT is a practical and effective
      screening tool for assessing oral self-care ability in the elderly.

PMID- 7716698
TI  - The oral hygiene performance test: development and validation of dental dexterity
      scale for the elderly.
AB  - This paper describes a test which was developed for use in assessing the
      functional oral hygiene status of an elderly population. The instrument was
      tested among 80 community-dwelling elderly subjects 65 or more years old. The
      instrument, the Oral Hygiene Performance Test [OHPT], is a direct-observation
      measure which objectively quantifies the individual's ability to perform oral
      hygiene and thus reduces subjective evaluation. The test utilized several items
      from other already-validated instruments currently in use in geriatric medicine
      to assess functional abilities in a geriatric population. Additional items were
      developed by the research team and were included in this 17-item test. The OHPT
      was validated with common measures of physical function and direct-observation
      measures. Construct validity was assessed by comparison of the OHPT scores with
      other commonly used measures of other dimensions. The instrument proved to be
      reliable and demonstrated construct as well as concurrent validity. It appears
      that the OHPT can prove useful to clinicians in assessing the oral physical
      function of elderly patients with regard to their maintenance of oral hygiene.
      Because the OHPT is a direct-observation instrument, it can even elicit higher
      functions in elderly patients. While effective among the studied population, the
      instrument may still need to be validated among more diverse populations, such as
      various ethnic groups and demented or severely impaired populations.

PMID- 7716700
TI  - Clinical and microbiological effects of chlorhexidine and arginine sustained
      release varnishes in the mentally retarded.
AB  - Local applications of sustained-released varnishes of chlorhexidine and arginine
      were used in a controlled pilot study of 34 mentally retarded patients, ages 18
      45, assigned to one of these groups: chlorhexidine (C), arginine (A), or placebo
      (P). A professional scaling followed by four weeks of professional brushing to
      reach a Plaque Index (PII) and Gingival Index (GI) of 1.0 at baseline preceded
      eight weeks of daily varnish application to the buccal and labial surfaces of all
      teeth. Clinical parameters (PII and GI) and bacterial samples from selected teeth
      were collected at predetermined intervals. Four and eight weeks following the
      baseline, the PII was significantly different among the groups, with the lowest
      score in the chlorhexidine group. No significant differences among the three
      groups were noted for the GI. The chlorhexidine and arginine groups showed
      significant reductions (p < 0.05 and p < 0.01, respectively) in the number of S.
      mutans. The arginine group showed a nonsignificant increase in the number of S.
      sanguis. These results suggest that the topical antimicrobial agents may have
      some relevance to plaque control among patients with mental retardation.

PMID- 7716701
TI  - Relationship of oral microflora with oral health status in Parkinson's disease.
AB  - Parkinson's disease (PD) patients report an increased craving for sweets, which
      may have an effect on microflora. We compared patients of PD who crave sweets
      with PD patients who do not. Age- and sex-matched control subjects were used,
      with 14 subjects in each group. A plaque sample was taken from tooth #18 with a
      curette and placed into RTF, homogenized, and plated onto selective and non
      selective media. Microflora were expressed as % CFU's of total anaerobes.
      Statistical analysis was performed by ANOVA and Newman-Keuls on log-transformed
      data. No statistical difference was observed among the three groups for
      lactobacilli, bacteroides, fusobacteria, veillonella, and actinomyces. S. mutans
      was lower in controls than in PD patients. Apparently, the craving for sweets in
      PD patients does not result in a significant increase in % of total anaerobes of
      certain microflora. PD patients showed a significant increase in mucositis
      compared with the control groups.

PMID- 7716702
TI  - Mechanisms of genetic control of murine systemic lupus erythematosus.

PMID- 7716705
TI  - Antibodies to CD45 and other cell membrane antigens in systemic lupus
      erythematosus.

PMID- 7716703
TI  - The role of cytokines in the immunopathogenesis of lupus.

PMID- 7716707
TI  - Lupus pregnancies and neonatal lupus.

PMID- 7716706
TI  - Antiphospholipid antibodies and the antiphospholipid syndrome.
AB  - The study of aPL antibodies and the APS has appealed to large numbers of
      investigators over the last decade. This accounts, in part, for the great degree
      of apparently contradictory data being published. What seems certain is that
      these antibodies are associated with thrombosis and recurrent pregnancy loss, and
      animal data suggest a direct role in pathogenesis. In vitro studies demonstrate
      that these antibodies have a variety of functional effects on the hemostatic
      system, giving further credence to an antibody role in thrombosis. Further
      studies will doubtless give better insight into the mechanisms of antibody action
      and this will provide a more rational basis for treatment.

PMID- 7716710
TI  - Drug combination therapy of systemic lupus erythematosus.

PMID- 7716708
TI  - Systemic lupus erythematosus in children.

PMID- 7716709
TI  - Systemic lupus erythematosus--disease management.

PMID- 7716704
TI  - The cytokine network in the pathogenesis of systemic lupus erythematosus and
      possible therapeutic implications.

PMID- 7716712
TI  - Extracorporeal photochemotherapy for the treatment of lupus erythematosus:
      preliminary observations.

PMID- 7716711
TI  - Central nervous system involvement in systemic lupus erythematosus: a new
      therapeutic approach with intrathecal dexamethasone and methotrexate.
AB  - In systemic lupus erythematosus (SLE), neurological involvement has been reported
      to occur with frequencies ranging from 14% (severe cases) to 83% (mild forms
      included). In spite of early diagnosis and aggressive treatment, neuropsychiatric
      SLE may represent a serious problem of management. We describe three cases, one
      with acute transverse myelitis, one with hemiparesis, and one with signs of focal
      and diffuse cerebral dysfunction, in whom improvement following intrathecal
      therapy with methotrexate and dexamethasone was observed.

PMID- 7716713
TI  - Immunological intervention reveals reciprocal roles for tumor necrosis factor
      alpha and interleukin-10 in rheumatoid arthritis and systemic lupus
      erythematosus.

PMID- 7716714
TI  - Prognosis in systemic lupus erythematosus.

PMID- 7716715
TI  - Gunshot injuries of the liver: the Baragwanath experience.
AB  - BACKGROUND: This study comprised 304 patients with gunshot injuries of the liver,
      many of which from high-velocity firearms. The purpose of this study is to
      evaluate our management policy in gunshot injuries of the liver in light of our
      recent wider experience. METHODS: All grade I and II injuries and most grade III
      injuries were managed by simple operative measures, without postoperative
      mortality directly related to the liver trauma. RESULTS: Grade III, IV, and V
      injuries had 8.5%, 52%, and 16% resectional debridement rates and 8.5%, 38%, and
      84% perihepatic packing rates, respectively. In the resectional debridement group
      the postoperative mortality rate was 15% (half the deaths were directly caused by
      the hepatic injury). The postoperative mortality rate in the perihepatic packing
      group was 31.5% of which 45% of deaths were due to ongoing bleeding, 27.5% to
      sepsis, and 27.5% to associated trauma. The septic complications were less common
      when packs were removed early. CONCLUSIONS: We suggest that resectional
      debridement and perihepatic packing should be liberally applied in the most
      severe grade III, most grade IV, and grade V gunshot injuries of the liver and
      that perihepatic packing should be removed as early as the physiologic
      derangements are corrected. Our experience with grade VI injuries is very
      limited, and their management should be studied in larger series.

PMID- 7716717
TI  - Magnetic resonance imaging and hepatic hemodynamics: correlation with metabolic
      function in liver transplantation candidates.
AB  - BACKGROUND: Preoperative assessment of orthotopic liver transplantation
      candidates requires definition of both the anatomy and metabolic function of the
      native liver. Current evaluation techniques combine computed tomographic
      scanning, duplex ultrasonography with blood chemistry analysis, and physical
      stigmata of end-stage liver disease. Recently, magnetic resonance imaging (MRI)
      has emerged as an alternative method for delineation of hepatic and portal venous
      anatomy. In addition, MRI accurately measures hepatic volume and portal venous
      blood flow. METHODS: To examine the role of MRI-derived indexes of hepatic
      hemodynamics in the preoperative assessment of liver function, 39 consecutive
      liver transplantation candidates were studied in a prospective manner. Liver
      function (aspartate aminotransferase), alanine aminotransferase, alkaline
      phosphatase, total bilirubin, and albumin levels), hematologic indexes (complete
      blood cell count, prothrombin time), and Child's classification were determined
      at the time of evaluation. Axial breath-held multiplanar spoiled-gradient echo
      MRI measured hepatic volume, whereas a cine phase-contrast sequence perpendicular
      to the portal vein measured flow. RESULTS: Hepatic index, defined as hepatic mass
      corrected for body surface area, was found to correlate with prothrombin time (p
      < 0.04) and platelet count (p < 0.03) by multivariate regression analysis. Portal
      flow index (PFI), defined as portal flow corrected for hepatic mass), was
      associated with aspartate aminotransferase (p < 0.02), alanine aminotransferase
      (p < 0.04), and albumin (p < 0.03) by multivariate regression analysis. In
      addition, PFI was closely correlated with the patients' functional status as
      determined by Child's classification system. Increasing values of PFI were
      associated with declining hepatic functional reserve. Child's class A patients
      had a mean PFI that was two times less than that of Child's class B patients
      (0.26 +/- 0.04 versus 0.04 +/- 0.06 ml/min/gm; p < 0.02) and five times less than
      that of Child's class C patients (0.26 +/- 0.04 versus 1.05 +/- 0.14 ml/min/gm; p
      < 0.001). Similarly, the mean PFI associated with Child's class B was two times
      less than that of Child's class C (0.46 +/- 0.06 versus 1.05 +/- 0.14 ml/min/gm;
      p < 0.01). These data show that MRI-derived indexes of portal hemodynamics and
      hepatic mass (1) correlate well with biochemical indexes of hepatic dysfunction
      and (2) serve as anatomic and hemodynamic correlates to Child's functional
      classification. CONCLUSIONS: We conclude that MRI may serve to noninvasively
      delineate preoperative hepatic vascular anatomy and metabolic dysfunction in
      candidates undergoing examination for liver transplantation.

PMID- 7716716
TI  - Immunoregulatory effects of CD4+ T helper subsets in human melanoma.
AB  - BACKGROUND: The elucidation of CD4+ T helper (Th) cell traits is important for
      the understanding of immunoregulatory mechanisms in patients with cancer, in
      particular the Th-cell effect on cytotoxic CD8+ tumor-specific lymphocytes (CTL).
      METHODS: Sixty-six T-cell receptor alpha beta+/CD4+ clones were generated from
      tumor-infiltrating lymphocytes of five patients with melanoma and classified into
      subsets by cytokine production. Transwell experiments were performed to test how
      the soluble factors of each Th-clone subset affected the cytotoxicity of the
      tumor-specific CTL against autologous tumor. RESULTS: Th0 clones enhanced
      cytotoxicity of the CD8+ CTL compared with control CTL cultured in cytokine-free
      medium. Th1-clone supernatant also enhanced cytotoxicity by CD8+ CTL. In
      contrast, Th2 clones decreased killing compared with control CTL. Replacement of
      the Th clones by exogenous interleukin (IL)-2 in concentrations similar to that
      produced by Th0 and Th1 clones enhanced cytotoxicity. However, suppression of
      cytotoxicity was observed when similar concentrations of IL-4 were added instead.
      The helper effect of Th0-soluble factors could be inhibited by anti-IL-2
      antibody, whereas anti-IL-4 antibody did not show a significant enhancement.
      CONCLUSIONS: The majority of the CD4+ tumor-infiltrating lymphocytes (Th0) in
      patients with melanoma enhance the CTL response to autologous tumor by their
      soluble factors, whereas Th2 cells suppress the CTL response.

PMID- 7716720
TI  - Parathyroidectomy in primary hyperparathyroidism: preoperative localization and
      routine biopsy of unaltered glands are not necessary.
AB  - BACKGROUND: An assessment was made of operative risk and outcome after
      parathyroidectomy for primary hyperparathyroidism. METHODS: A retrospective study
      was conducted in a single center university hospital in Switzerland. The 173
      patients (130 women and 43 men) ranged from 17 to 89 years of age (mean, 62.0
      years). No routine preoperative localization methods were used for primary neck
      exploration. Parathyroidectomy was performed under general anesthesia. No routine
      use was made of intraoperative biopsy of glands whose macroscopic appearance was
      normal. The 173 patients underwent 179 operations (170 primary and 9 secondary
      interventions). Resection of a single gland was performed in 127 cases (73.4%)
      and of two glands in 36 cases (20.8%). Subtotal parathyroidectomy (3 1/2 glands)
      was performed in 10 cases (5.8%). RESULTS: Of 170 patients with primary
      intervention, 164 (96.5%) were normocalcemic after operation. Six of 170 patients
      (3.5%) underwent early reexploration. Three additional patients underwent late
      secondary procedures. These nine secondary operations were successful in seven
      patients (78%). At follow-up (mean, 24.7 months after operation) normocalcemia
      was noted in 163 of 171 patients (95.3%). Persistent and recurrent
      hyperparathyroidism occurred in 1.2% and 3.5% of patients, respectively.
      Permanent postoperative hypoparathyroidism was noted in 4% (six of seven patients
      underwent a subtotal parathyroidectomy for multiglandular hyperplasia). Operative
      morbidity and mortality were 2.3% and 0.6%, respectively. CONCLUSIONS: Our
      surgical strategy for treatment of primary hyperparathyroidism has proved to be
      safe with a favorable outcome in more than 95% of patients. This was possible
      without the routine use of preoperative localization studies and intraoperative
      biopsy of macroscopically normal glands. Routine biopsy of normal-appearing
      glands seems to be unnecessary and may increase the risk of hypoparathyroidism.

PMID- 7716718
TI  - Lymphatic invasion and potential for tumor growth and metastasis in patients with
      gastric cancer.
AB  - BACKGROUND: Lymph node metastasis is a risk factor for the occurrence of
      peritoneal dissemination and liver metastasis in patients with gastric cancer.
      METHODS: We analyzed data on 324 patients with serosally invasive gastric cancer
      with respect to the relation between lymphatic invasion and potential for tumor
      growth and metastasis. All these patients were curatively treated in the
      Department of Surgery II, Kyushu University. RESULTS: Lymphatic invasion was
      evident in 214 patients, in whom vascular invasion was more frequent and the rate
      of lymph node metastasis was higher compared with patients with no lymphatic
      invasion. There was no difference in tumor size. The type of recurrence varied,
      and the prognosis was poor in patients with lymphatic invasion. The DNA ploidy
      pattern was higher, and the levels of proliferating cell nuclear antigen labeling
      and argyrophilic nucleolar organizer regions count were significantly higher in
      tumor tissues with lymphatic invasion than in those without invasion.
      CONCLUSIONS: Gastric cancers with characteristics of lymphatic invasion have
      higher proliferating activities, and metastases to distant organs are likely.

PMID- 7716719
TI  - Mutational analysis of multiple endocrine neoplasia type 2A associated with
      Hirschsprung's disease.
AB  - BACKGROUND: The clinical association of multiple endocrine neoplasia type 2A (MEN
      2A) and Hirschsprung's disease (HD), although rare, has been previously observed.
      Recently, germline mutations in the RET proto-oncogene, a transmembrane receptor
      with tyrosine kinase activity, have been detected in patients with familial HD.
      RET is also the predisposition gene for the inherited cancer syndrome MEN 2A.
      METHODS: We describe a DNA sequence variation within the coding region of RET in
      two large unrelated kindreds with MEN 2A (with 83 and 42 persons affected) in
      which HD cosegregated with MEN 2A in seven patients. Mutational analysis was
      performed with a highly sensitive polymerase chain reaction-based denaturing
      gradient gel electrophoresis technique followed by direct sequencing of mutants.
      RESULTS: Genetic analysis by denaturing gradient gel electrophoresis detected
      mutant bands in RET exon 10 in patients with MEN 2A from both kindreds. Direct
      DNA sequencing of mutants revealed a thymine-to-adenine base change in codon 618,
      resulting in a cysteine-to-serine substitution. The identical mutation was
      present in all seven children with HD. Of these children five underwent
      thyroidectomy for C-cell abnormalities; one 3-year-old child is awaiting thyroid
      surgery, and the remaining patient died at age of 12 weeks. CONCLUSIONS: The RET
      codon 618 Ser mutation could predispose patients with MEN 2A to HD. RET may
      assume a critical role in embryologic enteric nerve migration and tumorigenesis
      of cells from neural crest lineage.

PMID- 7716721
TI  - Should primary hyperparathyroidism be treated surgically in elderly patients
      older than 75 years?
AB  - BACKGROUND: Diagnosis of primary hyperparathyroidism (PHPT) is increasingly
      suspected in elderly patients after the discovery of hypercalcemia by routine
      measurement of serum calcium levels. Surgery is commonly accepted as the optimal
      treatment of PHPT. We wanted to assess risk and results of neck exploration in
      elderly patients with PHPT. METHODS: We performed a retrospective study of the
      charts of 78 patients older than 75 years (mean age, 79.1 years) with PHPT who
      underwent neck exploration during a 15-year period. RESULTS: The most common
      presenting symptoms were neurologic and psychiatric disorders (47 patients).
      Preoperative localization investigations, performed in 72 patients, were
      successful in 42 of them (sensivity, 58%). Single adenoma, double adenomas, and
      hyperplasia were found in 74 patients (95%), three patients, and one patient,
      respectively. Overall postoperative mortality was 3.8% (three patients) with no
      death since 1984. Significant complications occurred in three patients (4%): one
      myocardial infarction, one pulmonary embolism, and one cerebral hemorrhage.
      Average length of postoperative hospital stay was 4 days. Among patients who
      could be followed up (65 cases with a mean follow-up of 3 years), 94% reported an
      improvement in their symptoms. This was especially marked for fatigue and
      intellectual function. CONCLUSIONS: These data support a liberal approach
      regarding surgical treatment in elderly patients with PHPT.

PMID- 7716722
TI  - Pulsatile nature of growth hormone levels in critically ill trauma victims.
AB  - BACKGROUND: Circulating growth hormone (GH) levels in normal persons fluctuate
      widely because of pulsatile GH secretion. It is not known whether this pulsatile
      nature and rhythmicity exist in severe injury. These data become necessary to
      decide the timing of supplementary GH administration for its optimal utilization.
      The purpose of this study was to investigate the GH circadian variation with
      respect to that of insulin-like growth factor-1 (IGF-1), insulin, C-peptide, and
      cortisol in the early flow phase of injury. METHODS: Plasma GH, IGF-1, insulin, C
      peptide, and cortisol levels were measured at 1-hour intervals during 24 hours (8
      AM to 8 AM) in 10 severely injured adults with multiple trauma during the early
      catabolic flow phase 24 to 48 hours after injury, when patients received
      maintenance fluids without calories or nitrogen. RESULTS: The 24-hour integrated
      GH concentration is not different from either 12-hour mean diurnal or 12-hour
      mean nocturnal or mean 8 AM GH concentration. Pulsatile GH bursts persist in
      injured patients during both day and night. Pulsatile bursts do not exist for IGF
      1, insulin, and C-peptide. The plasma levels of cortisol show time-dependent
      daily maximum and minimum levels. CONCLUSIONS: Pulsatile GH bursts persist in
      injured patients but less frequently than seen in normal persons. The time of
      bolus administration of GH to augment the anabolic GH action in patients with
      trauma does not matter; however, for convenience morning administration may be
      preferable for patients in the intensive care unit.

PMID- 7716723
TI  - Flow patterns and preferred sites of intimal thickening in end-to-end anastomosed
      vessels.
AB  - BACKGROUND: Fluid mechanical factors are suspected to be involved in the
      pathogenesis and localization of intimal hyperplasia in anastomosed vessels.
      However, no direct correlation has been established between the flow and the
      exact sites of intimal hyperplasia. Hence we have studied the relationship
      between the flow and preferred sites of wall thickening in 90-degree- and 45
      degree-cut and end-to-end anastomosed vessels. METHODS: Twenty-five 90-degree and
      twenty-five 45-degree end-to-end anastomoses were performed on the femoral
      arteries of 17 adult mongrel dogs. The vessels were harvested at 3 months after
      operation, fixed at 100 mm Hg, dehydrated with ethanol, and rendered transparent
      by immersing them in methyl salicylate. Exact locations and sizes of intimal
      thickening and characteristics of the flow prevailing at sites of anastomoses
      were studied in detail by means of flow visualization and cinemicrographic
      techniques. RESULTS: It was found that a perfect correlation exists between the
      preferred sites of intimal thickening and the regions of slow recirculation flows
      with low wall shear stresses. In both 90-degree and 45-degree anastomosed
      vessels, intimal thickening developed only in those vessels in which formation of
      slow recirculation flows was observed. It was also found that although a
      pronounced and localized intimal thickening developed in 45-degree anastomosed
      vessels, the degree of circumferential constriction caused by both surgical
      procedures and development of intimal thickening was much milder in 45-degree
      than 90-degree anastomosed vessels. CONCLUSIONS: The results suggest that key
      hemodynamic factors involved in the localization of intimal thickening in end-to
      end anastomosed vessels are low velocity of flowing blood and the resultant low
      shear stresses acting on the vessel wall.

PMID- 7716724
TI  - Pathologic duodenogastric reflux associated with persistence of symptoms after
      cholecystectomy.
AB  - BACKGROUND: The aim of this study was to determine whether increased
      duodenogastric reflux contributes to postcholecystectomy symptoms. METHODS:
      Gastric pH monitoring, hepatobiliary scintigraphy, gastric emptying scans, and
      gastric acid analysis were performed in asymptomatic (n = 10) and in symptomatic
      (n = 27) patients after cholecystectomy. Normal subjects (n = 20), patients with
      dyspepsia related to gastric acid hypersecretion (n = 20), patients with reflux
      gastritis after gastric surgery (n = 10), and patients with confirmed primary
      pathologic duodenogastric reflux (n = 10) were studied as controls. Symptomatic
      patients also underwent upper gastrointestinal endoscopy. RESULTS: Symptomatic
      patients had significantly increased interprandial gastric exposure to pH < 3
      compared with asymptomatic subjects, which correlated well with a high incidence
      of hepatobiliary scans positive for abnormal duodenogastric reflux and chronic
      gastritis on endoscopy. Gastric alkaline exposure in symptomatic patients was
      similar to that seen in patients with primary pathologic duodenogastric reflux
      and patients with duodenogastric reflux related to gastric surgery. Gastric acid
      secretion and gastric emptying were not altered. Five patients tested before and
      after laparoscopic cholecystectomy showed that nocturnal gastric alkalization was
      enhanced after operation. CONCLUSIONS: This study suggests that excessive
      duodenogastric reflux may be responsible for persistence of symptoms after
      cholecystectomy.

PMID- 7716725
TI  - Use of technetium 99m diethylenetriamine-pentaacetic acid-galactosyl-human serum
      albumin liver scintigraphy in the evaluation of preoperative and postoperative
      hepatic functional reserve for hepatectomy.
AB  - BACKGROUND: Technetium 99m diethylenetriaminepentaacetic acid-galactosyl-human
      serum albumin (99mTc-GSA) is a new liver scintigraphy agent that binds to the
      asialoglycoprotein receptors. We evaluated the clinical use of 99mTc-GSA for the
      perioperative assessment of hepatectomy. METHODS: Thirty-six patients with
      hepatocellular carcinoma were admitted for elective hepatectomy. 99mTc-GSA
      scintigraphy was obtained after the intravenous injection of 99mTc-GSA, and a
      modified receptor index (MRI) was calculated. 99mTc-GSA scintigraphy,
      conventional liver function, the plasma disappearance rate, and the 15-minute
      retention rate of indocyanine green (ICGR15) were carried out before operation
      and every 1 to 3 months after operation. The relationships between several
      systemic hemodynamic parameters, histologic activity index (HAI), plasma
      disappearance rate, and ICGR15 or MRI values were estimated. RESULTS: A
      significant correlation was obtained between the MRI and ICGR15 (r = 0.6231, p <
      0.001). Plasma disappearance rates correlated well with systolic volume and left
      cardiac work, whereas MRI values did not correlate with these systemic
      hemodynamics. Preoperative discrepancies between the values of MRI and ICGR15
      were seen in eight cases. In these cases the MRI values correlated well with HAI
      scores (p < 0.05) but there was no significant correlation between ICGR15 values
      and the HAI scores. CONCLUSIONS: These results suggested the use of 99mTc-GSA
      scintigraphy as a easy and reliable method for determining liver functional
      reserve.

PMID- 7716726
TI  - Hypercalcemia decreases bile flow and increases biliary calcium in the prairie
      dog.
AB  - BACKGROUND: Biliary calcium is known to play an important role in the
      pathogenesis of gallstones. Calcium salts are present in all pigment gallstones
      and are also present in the core of most, if not all, cholesterol gallstones.
      METHODS: The effects of acute hypercalcemia on bile flow and biliary calcium
      secretion were examined in 22 prairie dogs during intravenous taurocholate
      infusion (0, 1.0, 2.25, and 4.5 mumol/kg/min). RESULTS: Bile flow was linearly
      correlated with bile acid output in both control (y = 7.62x + 13.5, r = 0.98) and
      hypercalcemic (y = 7.00x + 10.4, r = 0.96) animals. At lower bile acid outputs (<
      3.0 mumol/kg/min), biliary ionized calcium output per increment bile acid output
      was significantly increased in hypercalcemic animals (0.016 versus 0.011 mumol
      Ca++ mumol taurocholate, p < 0.001). Bile ionized calcium concentrations
      approximated Gibbs-Donnan predicted values only at low bile flow rate.
      CONCLUSIONS: Hypercalcemia decreases bile flow and increases biliary ionized
      calcium concentration in the prairie dog. These effects favor the precipitation
      of calcium salts in bile.

PMID- 7716727
TI  - Effect of patient factors on hospital costs for major bowel surgery: implications
      for managed health care.
AB  - BACKGROUND: We examined the effects of patient factors on hospital resource
      consumption for patients who had undergone major bowel operation (diagnosis
      related groups [DRGs] 148 and 149) at an urban, university hospital. METHODS: We
      performed cross-sectional analysis of computerized hospital discharge abstracts
      and charts of 491 consecutive discharges in these DRGs. Total hospital charges
      and length of stay were dependent variables. Independent variables included
      admission status, admission service, previous admissions, payer type, service
      type, diagnosis, reoperation, and death. RESULTS: Patient factors accounted for
      significant variability in resource consumption. By univariate analysis all of
      the above variables significantly affected total charges, and all but service
      type significantly affected length of stay. By multivariate analysis DRGs 148/149
      alone explained 4.2% of the variance, whereas all the variables together
      increased R2 to 52.1%. Logistic regression of reoperation and of death as
      dependent variables suggested that patient factors also accounted for significant
      variance in these outcomes. CONCLUSIONS: Because patient factors may not be
      directly controllable by hospitals or physicians, differences among hospitals in
      costs and in "quality" may relate more to differences in patient mix than to
      efficiency. DRGs alone are not a sufficient management tool, and additional
      measures are needed to adequately measure both efficiency and quality.

PMID- 7716728
TI  - Endorectal pull-through of transplanted colon as part of intestinal
      transplantation.
AB  - BACKGROUND: Two children with life-threatening disorders underwent intestinal
      transplantation; one multivisceral transplantation excluding the liver, and the
      second transplantation of the liver, small bowel, and colon. METHODS: Involvement
      of the native rectum necessitated resection and replacement with the transplanted
      allograft. To prevent a permanent colostomy, a pull-through of the allograft
      colon was performed. RESULTS: Both patients had a stormy early postoperative
      course, mainly because of the complexities of intestinal transplantation, but
      with eventual recovery, including improvement of rectal function. CONCLUSIONS:
      These are the first two known cases in which a transplanted large intestine was
      used for a pull-through procedure.

PMID- 7716729
TI  - Role of physical examination in detection of abdominal aortic aneurysms.
AB  - BACKGROUND: Early detection of asymptomatic abdominal aortic aneurysms (AAAs) has
      been advocated to decrease the high mortality rate of ruptured AAAs. The purpose
      of this study was to document how AAAs were detected, whether AAAs not detected
      on physical examination (PE) were palpable, and what factors precluded detection
      by PE. METHODS: Two hundred forty-three patients undergoing elective infrarenal
      AAA repair at a Veterans Affairs, county, or university hospital during a 10-year
      period were analyzed retrospectively. The method of initial detection of the AAA,
      size of the AAA at initial detection and before repair, and whether the AAA was
      palpable on preoperative PE were recorded, and the body mass index [BMI; weight
      in kg/(height in meters)2] was calculated. Obese patients were defined with BMI
      of greater than 85th percentile. RESULTS: Only 93 (38%) patients had their AAAs
      initially detected by PE; the remainder (62%) were found incidentally on
      radiologic examinations performed for other indications. Patients with AAAs
      detected by PE had lower BMIs (PE, 23.7 +/- 3.6 kg/m2; incidental, 26.0 +/- 4.6
      kg/m2, p < 0.001), but there was no difference in AAA size (PE, 5.8 +/- 1.6 cm;
      incidental, 5.5 +/- 1.9 cm, not significant). Forty-three percent of patients
      with AAAs detected on radiologic examination had palpable AAAs and should have
      been detected on PE. Overall, 55 (23%) AAAs were not palpable on preoperative PE,
      even when the diagnosis was known. Obese patients had only 15% of AAAs detected
      by PE, and only 33% were palpable. CONCLUSIONS: AAAs are underdiagnosed by PE,
      especially in obese persons. More widespread abdominal examination to detect a
      widened aortic pulse would improve detection of AAAs.

PMID- 7716730
TI  - Adrenal surgery for hypercortisolism--surgical aspects.
AB  - BACKGROUND: Patients with endogenous hypercortisolism are thought to be at high
      risk for adrenalectomy and may experience significant postoperative surgical
      mortality/morbidity. METHODS: From 1981 through 1991, 91 patients underwent
      adrenal resection for endogenous hypercortisolism. Causes were adrenal-dependent
      Cushing's syndrome (50%), pituitary-dependent Cushing's syndrome (27%), and an
      ectopic adrenocorticotropic hormone-secreting tumor (23%). Causes of adrenal
      dependent Cushing's syndrome were adrenocortical adenoma (72%), bilateral nodular
      hyperplasia (20%), and adrenocortical carcinoma (8%). Comparative mean length of
      hospitalization for patients undergoing unilateral anterior versus posterior
      approach was 8 versus 6 days, and bilateral anterior versus posterior was 11
      versus 6 days. RESULTS: Operative mortality was 2.6%. Only one patient had a
      wound infection, and no patient had either a venous thrombosis or a pulmonary
      embolism. Delayed wound healing occurred in three patients. CONCLUSIONS: (1)
      Adrenal surgery can be performed today with low morbidity/mortality. (2) Although
      there is an effect of hypercortisolism on wound healing, infection, diabetes,
      hypertension, coronary artery disease, and pulmonary embolism, it was possible to
      perform adrenalectomy surgically with acceptable morbidity and mortality. (3)
      These results may serve as a standard against which laparoscopic adrenalectomy
      may be compared.

PMID- 7716731
TI  - Resectable leiomyosarcoma of inferior vena cava extended into the right atrium
      with the use of cardiopulmonary bypass and graft replacement.

PMID- 7716732
TI  - Choledochocele: newer concepts of origin and diagnosis.

PMID- 7716733
TI  - Laparoscopic cholecystectomy and gallbladder cancer.

PMID- 7716735
TI  - Interactive developmental toxicity of radiofrequency radiation and 2
      methoxyethanol in rats.
AB  - Concurrent exposures to chemical and physical agents occur in the workplace;
      exposed workers include those involved with the microelectronics industry,
      plastic sealers, and electrosurgical units. Previous animal research indicates
      that hyperthermia induced by an elevation in ambient temperature can potentiate
      the toxicity and teratogenicity of some chemical agents. We previously
      demonstrated that combined exposure to radiofrequency (RF; 10 MHz) radiation,
      which also induces hyperthermia and is teratogenic to exposed animals, and the
      industrial solvent, 2-methoxyethanol (2ME), produces enhanced teratogenicity in
      rats. The present study replicates and extends the previous research
      investigating the enhanced teratogenicity of combined RF radiation and 2ME
      exposures. The interactive dose-related teratogenicity of RF radiation (sham
      exposure or maintaining colonic temperatures at 42.0 degrees C for 0, 10, 20, or
      30 min) and 2ME (0, 75, 100, 125, or 150 mg/kg) was investigated by administering
      various combinations of RF radiation and 2ME to groups of rats on gestation days
      9 or 13; gestation-day 20 fetuses were examined for external, skeletal, and
      visceral malformations. The results are consistent with and extend our previous
      research findings. Synergism was observed between RF radiation and 2ME for some
      treatment combinations, but not for others. The study also clarified which
      gestational periods, RF radiation exposure durations, and 2ME doses would be most
      informative in future interaction studies to determine the lowest interactive
      effect level. Day 9 exposures generally evidenced little effect by 2ME, either by
      itself or in combination with RF radiation. In contrast, day 13 exposures
      resulted in highly significant effects from 2ME and RF radiation. The structures
      showing strong evidence of effects from both 2ME and RF radiation after exposure
      on gestation day 13 were the forepaw digits, forepaw phalanges, hindpaw digits,
      hindpaw phalanges, hind limbs, metacarpals, and metatarsals. Statistical analyses
      did not show a global synergistic effect, but did show evidence for a synergistic
      effect at intermediate levels of the dose ranges. Future research will address
      potential interactions at lower doses.

PMID- 7716734
TI  - Staurosporine does not prevent adrenergic-induced situs inversus, but causes a
      unique syndrome of defects in rat embryos grown in culture.
AB  - Staurosporine, an alkaloid isolated from Streptomyces species, is commonly used
      as a protein kinase C (PKC) inhibitor in animal investigations. In the present
      study, we used this compound to determine whether alpha 1-adrenergic stimulation
      induced situs inversus in rats is mediated by PKC. Embryos were explanted at 8
      A.M. on day 9 of gestation. Those with a neural groove but with no visible neural
      folds (Stage 11a) were selected and were cultured in medium containing various
      concentrations of staurosporine with or without 50 microM of phenylephrine, an
      alpha 1-adrenergic agonist. At 10 A.M. on day 11 of gestation, embryos were
      examined for situs inversus and other abnormalities. Staurosporine, tested at
      0.0001, 0.001, 0.01, 0.1, 0.375, and 0.5 microM (lethal concentration), did not
      block phenylephrine-induced situs inversus at any concentration. However,
      staurosporine alone produced situs inversus at concentrations above 0.1 microM.
      At 0.5 and 1.0 microM, staurosporine also caused cyst-like lesions projecting
      dorsally from the mesencephalon that we named "mesencephalic vesicles" and the
      formation of secondary somites. To confirm and further examine these unique
      effects of staurosporine both grossly and histologically, we conducted additional
      experiments using staurosporine from another source. Embryos were explanted
      between 6 A.M. and 9 P.M. on day 9 of gestation and were placed in one of the
      following groups according to their stage of development: 10b, 11a, 11b, 11c,
      12/s1-2, 12/s3-4, and 12/s5-6. Embryos were then cultured with various
      concentrations of staurosporine. Those cultured from Stage 11a exhibited similar
      lesions to those seen in the initial experiment but at somewhat higher
      concentrations of staurosporine. Embryos cultured from Stage 10b showed a similar
      pattern of lesions as seen at Stage 11a, except that higher concentrations of
      staurosporine were required to cause mesencephalic vesicles and secondary somites
      formation. Embryos cultured from Stage 11b showed similar effects to those
      cultured from younger stages except that maximum incidences of situs inversus
      were much lower. Those cultured from Stage 11c showed similar dose-response to
      those cultured from Stage 11b except that the incidence of secondary somites
      formation was much higher. In addition, in approximately 40% (n = 25) of embryos
      treated with greater than 1.0 microM of staurosporine, the growing end of the
      allantois did not reach the chorion and remained unattached in the exocoelomic
      cavity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7716736
TI  - Distribution of cellular retinoic acid-binding proteins I and II in the chick
      embryo and their relationship to teratogenesis.
AB  - The distribution of cellular retinoic acid-binding proteins I and II (CRABP I and
      II) during the first 6 days of chick development has been investigated using
      immunoblotting. Since retinoic acid (RA) is teratogenic to some parts of the
      embryo, stimulatory to other parts, and has no effect on others it may be that
      the distribution of cytoplasmic proteins such as CRABP I and II plays some role
      in this differential activity. Neither protein is expressed in the day 2 embryo,
      but from day 3 onwards both proteins are expressed and CRABP I is in considerable
      excess over CRABP II. Within the day 4 embryo there is some significant variation
      in the distribution according to tissue type. Neural tissues, neural crest
      derivatives, and limb buds most strongly express CRABP I whilst other tissues
      contain only moderate levels, and heart and epidermis do not express CRABP I at
      all. CRABP II has a widespread distribution, although at a lower level than CRABP
      I, with the exception of somites and ectoderm which do not express it at all. In
      the limb buds, there is a significant variation in CRABP I levels across the
      anteroposterior axis which suggests that these two CRABPs may have different
      functions during development. The relationship of these distributions in the
      embryo to the role of endogenous RA and the teratogenic effects of RA is
      discussed.

PMID- 7716737
TI  - 12-O-tetradecanoyl-phorbol-13-acetate-induced rat embryo malformations in vitro
      are associated with an increased relative abundance of embryonic E-cadherin mRNA.
AB  - Epithelial-cadherin (E-cadherin) is a member of a family of Ca(2+)-dependent cell
      adhesion molecules which are localized in zonulae adherens and play an important
      role during development. E-cadherin is abundant in rat embryos and their yolk
      sacs during organogenesis. The phorbol ester, 12-O-tetradecanoyl-phorbol-13
      acetate (TPA), has been reported to disrupt the morphology and functional
      development of the rat embryonic visceral yolk sac. The present study
      investigated the possibility that the effect of TPA on yolk sac development may
      be due to the altered expression of E-cadherin. Rat embryos, with their yolk sacs
      intact, were cultured on day 10 of gestation for 1 hr. At this time the vehicle,
      dimethyl sulfoxide (DMSO), or TPA (at different concentrations) was added to the
      culture medium; the cultures were continued for up to 24 hr. Embryos and yolk
      sacs were collected separately at the end of each culture period. The relative
      abundances of E-cadherin mRNA and protein were analyzed with Northern and Western
      blot analyses. Despite the TPA-induced abnormalities in yolk sac development, the
      relative abundance of E-cadherin mRNA or protein in the yolk sac was not altered
      by TPA exposure. However, in embryos exposed to dysmorphogenic concentrations of
      TPA, the relative abundance of E-cadherin mRNA was significantly increased after
      24 hr in culture, compared to either controls or embryos exposed to non
      dysmorphogenic concentrations of TPA. The magnitude of the increase in embryonic
      E-cadherin mRNA appeared to correlate with the severity of the embryo
      malformations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716739
TI  - 22nd annual conference of the European Teratology Society. 4th Scientific Meeting
      of the International Federation of Teratology Societies. Prague, Czech Republic,
      12-15 September 1994. Abstracts.

PMID- 7716738
TI  - Oxidative metabolism of aflatoxin B1 by lipoxygenase purified from human term
      placenta and intrauterine conceptal tissues.
AB  - Aflatoxin B1 (AFB1) is a teratogen in rodents and may be a human transplacental
      carcinogen. Although the presence of DNA adducts of AFB1 in the human placentas
      has been noted, the enzyme(s) responsible for the bioactivation was not
      identified. In this investigation, the linoleic acid (LA)-dependent cooxidation
      of AFB1 catalyzed by lipoxygenase (LO) purified by Con A affinity chromatography
      from the term placentas of nonsmokers was studied. HPLC chromatograms detected
      the presence of 5- and 15-HETE as the major metabolites and 12-HETE as a minor
      metabolite upon incubation of arachidonic acid (AA) with affinity purified human
      term placental LO. These results suggest that a mixture of LO isozymes is present
      in the affinity-purified enzyme preparations of term placentas. The optimal assay
      conditions to observe maximum rate of epoxidation included incubation of 250
      microM AFB1 with 80 micrograms LO and 3.5 mM LA at pH 7.2. AFB1-8,9-tris-diol
      produced in the reaction was estimated spectrofluorimetrically. A Vmax of 432 +/-
      26 pmol of AFB1-8,9-tris diol produced/min/mg protein and a Km of 77 microM for
      AFB1 were observed. The AFB1-8,9-tris-diol formation was dependent on the
      incubation time, concentration of enzyme protein, AFB1, and LA. LO catalyzed
      epoxidation of AFB1 was inhibited by NDGA, BHT, BHA, ETI, and gossypol. The
      evidence presented here clearly demonstrates that placental LO is capable of
      epoxidation of AFB1. Similar results were observed with LO preparations of human
      intrauterine conceptal tissues at 8-10 weeks of gestation.

PMID- 7716740
TI  - International study of sex ratio and twinning of neural tube defects.
AB  - The goal of this study, based on information collected from eight congenital
      malformation registry programs around the world, was to analyze sex and twinning
      of affected infants and fetuses, according to type of neural tube defect (NTD)
      and other variables. The type of defect and its location, whether it occurred in
      isolated form or was associated with other malformations, population from which
      data were retrieved, vital status of the infant, and gestational age of the
      fetus/infant were considered. The material included 3,416 infants and 168
      selectively aborted fetuses with anencephaly, 4,830 infants and 76 fetuses with
      spina bifida, and 1,022 infants and 19 fetuses with encephalocele. Less than 20%
      of infants with anencephaly or spina bifida and more than one-third of infants
      with encephalocele had associated malformations. A female excess was found among
      all infants with NTD but a male excess in fetuses delivered spontaneously before
      week 20, indicating selective male late fetal deaths. Sex ratio varied by type of
      NTD, vital status at birth, presence of associated malformations, and year of
      birth, with an increasing sex ratio for anencephaly during the 1960s and 1970s.
      Twinning was positively associated with NTD but the extent of this association
      varied with NTD type and program, while the distribution by sex type of pair of
      twin appeared to be similar to that of all births. Twins concordant for
      anencephaly or encephalocele were mainly found when the defect occurred as part
      of a syndrome, and only in like-sexed pairs. Twins concordant for spina bifida
      had the isolated form of the defect and 5 of 6 pairs were like-sexed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7716741
TI  - Neural plate microvillus lengthening in rat embryos grown in various
      concentrations of glucose and further studies of the mechanism.
AB  - Glucose is an important cellular nutrient, and in the early embryo, which is
      dependent mostly on anaerobic glycolysis, it is even more essential. Based on
      tissue culture cells in which glucose utilization has become membrane-limited, a
      concept has been developed that the tip of the microvilli is the entrance
      compartment for glucose and that the shaft sets up a diffusion barrier. An
      increase in length of the microvillus is associated with decreased entry of
      phosphorylated hexose into the cells. Our previous findings of lengthening of the
      microvilli of the neural plate cells after 40 min exposure to glucose at room
      temperature have been extended to a 17 hr whole embryo culture system. In
      cultures where the final concentration of glucose was 20 and 24 mg/dl there was
      embryonic death. In those cultures ending with 29-137 mg/dl of glucose the
      embryos developed normally. Those grown in dialyzed serum supplemented with B
      vitamins and glucose grew equally as well as those in whole rat serum. Somite
      numbers attained did not change with increasing glucose concentration but a
      modest increase in micromoles of glucose used per embryo was found, suggesting
      the presence of another source of energy at lower glucose concentrations. The
      average glucose utilization per gram of protein per hour was 844 mumol in these
      day 9.5-10 embryos and this compares to 733 mumol previously found using
      uniformly labeled 14C glucose on day 10.3. Lactate production averaged 85% of the
      glucose utilized. Pyruvate did not support growth in the absence of
      glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716742
TI  - Prevention of neural tube defects by and toxicity of L-homocysteine in cultured
      postimplantation rat embryos.
AB  - Mild hyperhomocysteinemia is frequently observed in mothers who gave birth to a
      child with a neural tube defect (NTD). In a previous study we showed L
      homocysteine was embryotoxic to gestational day 10 (GD10) rat embryos in culture,
      however, no NTDs were observed. We therefore investigated the effect of L
      homocysteine on the development of neural plate stage (GD9.5) rat embryos. Other
      objectives of this study were investigation into whether the embryotoxicity of L
      homocysteine could be attenuated by compounds related to its metabolism and
      clarification of the mechanism of L-homocysteine embryotoxicity. In GD9.5 rat
      embryos L-homocysteine was not toxic at 1- and 2-mM concentrations. Rather at
      these concentrations it promoted development of the rat embryos in serum that
      without supplementation caused NTDs in the embryos. L-Methionine had the same
      preventive effect at even lower concentrations, but folinic acid (1 mM) did not
      improve embryonic development. N5-Methyltetrahydrofolate (5-CH3-THF) (100
      microM), L-serine (6 mM), and L-methionine (6 and 12 mM) attenuated the
      embryotoxicity of L-homocysteine (6 mM) in GD10 rat embryos. Vitamin B12 (10
      microM) completely abolished the embryotoxicity of L-homocysteine, which was
      shown to be mediated by catalysis of the spontaneous oxidation of L-homocysteine
      to the less toxic L-homocystine. In GD11 rat embryos, both L- and D-homocysteine
      were readily taken up when added to the culture (3 mM) and increased embryonic S
      adenosylhomocysteine (SAH) levels 14- and 3-fold, respectively. This difference
      was shown to be caused by the stereospecific preference of SAH hydrolase. We
      propose the basis for L-homocysteine embryotoxicity is an inhibition of
      transmethylation reactions by increased embryonic SAH levels.

PMID- 7716743
TI  - Immunohistochemical double-staining for Ah receptor and ARNT in human embryonic
      palatal shelves.
AB  - The aryl hydrocarbon receptor (AhR) and the AhR nuclear translocator protein
      (ARNT) are basic-helix-loop-helix-PAS (HLH) proteins involved in transcriptional
      regulation. Polycyclic aromatic halogenated chemicals, of which 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) is the most potent, bind to the AhR. In the
      cellular cytoplasm, the AhR exists as a complex with the heat shock protein HSP90
      and other small peptides. This complex dissociates following ligand binding and
      then the ligand-bound AhR binds ARNT. The ligand-AhR-ARNT complex interacts with
      a specific, nuclear DNA sequence, the dioxin response element (DRE), altering
      transcription of a regulated gene. Studies in hepatoma cell lines indicate that
      both proteins are required for regulation of transcription. In this study, AhR
      and ARNT were localized immunohistochemically in human embryonic palatal cells
      and specific patterns of expression were seen for each protein. A double-staining
      protocol revealed that epithelial cells expressed both AhR and ARNT, but in
      mesenchyme and nasal spine cartilage individual cells were identified which
      expressed either AhR or ARNT. This heterogeneous pattern may be a means of
      suppressing transcriptional regulation and also suggests the existence of other,
      unidentified basic-helix-loop-helix partner(s). The heterogeneous expression
      pattern may also reflect a complex role for these HLH proteins as transcriptional
      regulators of embryonic development.

PMID- 7716744
TI  - Teratogen update: lead.

PMID- 7716745
TI  - [The nutritive value of carp (Cyprinus carpio)].
AB  - From January 1991 to February 1992 the composition of filleted carps was
      investigated. Special attention was given to a possible correlation to origin and
      season. The gutted, fresh fish were weighted and only the fillets were used for
      the investigation. All samples were analysed in duplicate by official methods.
      The results showed that the protein concentration ranged between 13.0 and 21.9%,
      the lipids content ranged between 0.3 and 23.9%, moisture ranged between 59.8 and
      84.2%, and ash content ranged between 0.0 and 1.6%.

PMID- 7716746
TI  - [The clinical case. Injury to a teat in a cow].

PMID- 7716747
TI  - [Pestivirus-induced changes in the central nervous system of ruminants].
AB  - This review article presents the pathomorphological and pathogenetic aspects of
      pestivirus-induced alterations of the central nervous system of ruminants
      following transplacental infections.

PMID- 7716748
TI  - [Clinical, diagnostic laboratory and therapeutic studies of mastitis in a large
      sheep breeding flock].
AB  - During two lambing seasons, 6500 ewes of a large sheep breeding unit were
      investigated. Within this period, 467 ewes suffered from mastitis. The morbidity
      was 3.8% and the lethality 4.7%. In 84% of the investigated animals udder
      pathogenic bacteria were detected. Mostly, Pasteurella haemolytica and
      Staphylococcus aureus were isolated as agents of ovine mastitis. Before and
      during the antibiotic therapy the clinical symptoms (general condition,
      temperature, milk appearance, consistency of the udder tissue) were recorded. The
      combined antibiotic therapy, which consisted of parenteral and local
      intracisternal applications, was mostly satisfactory concerning recovery from
      mastitis and survival of the ewes. Only 17 ewes died from mastitis; most deaths
      caused by Staphylococcus aureus.

PMID- 7716749
TI  - [The effectiveness in calves of subcutaneous vaccination with the Salmonella
      vaccine Murivac].
AB  - Subcutaneous administration of a Salmonella typhimurium bacterin, given twice in
      an interval of two weeks, protected calves against the oral infection with a
      Salmonella wild strain.

PMID- 7716750
TI  - [Clarification and treatment of teat stenosis using endoscopy].
AB  - In ten cows ten stenotic teats were endoscopically examined and treated. For this
      purpose two different methods were performed: Either the endoscopy was performed
      through the teat canal or through a small incision in the side of the teat. The
      endoscopy through the teat canal proved to be a simple and practical method.
      However, the results were not always clear-cut, and a controlled operation was
      not possible. Endoscopy through a side access is more expensive but has several
      advantages. It allows a good view on the Furstenbergsche Rosette, one of the most
      frequent locations of stenosis. Additionally, controlled operations of the level
      of the Furstenbergsche Rosette are possible once a suitable instrument has been
      introduced through the teat canal. The additional trauma caused by the access
      hole is a minor problem. All cows examined and treated by this method could be
      milked without any problems three days after the operation.

PMID- 7716751
TI  - [The sexual behavior of the African ostrich (Struthio camelus)].
AB  - The African ostrich (Struthio camelus) is different from other birds not only
      because it is a running bird (Ratitae), but also because it urinates and the male
      bird has a penis. On a specialized farm in Israel the sexual behaviour of
      ostriches was studied. Courtship behaviour and mating have a very refined
      pattern. The copulation, which starts with an immission of the penis and ends
      with an orgasm, lasts about one minute. Most of the copulations take place during
      the morning morning hours. Occasionally, female ostriches demonstrate courtship
      behaviour to other females. Sometimes female ostriches mount other females as in
      the case of copulation.

PMID- 7716752
TI  - [A herpesvirus-caused enzootic--Pacheco's parrot disease--in a psittacine
      collection].
AB  - After the official confirmation of psittacosis in a collection of psittacine
      birds a total of 40 of them died during treatment with tetracycline. 36 of them
      underwent post mortem examination. From 33 birds the causative herpesvirus of
      Pacheco's parrot disease (PPD) was isolated and/or a non-purulent hepatitis
      diagnosed, the latter a characteristic for PPD. The cause of the outbreak was
      assumed to be a latent herpesvirus infection of individual birds which was
      activated by various stress factors during the psittacosis treatment. The
      macroscopic and histologic lesions, the results of virological investigations and
      the in vitro effect of acyclovir on the multiplication of the isolated herpes
      virus are described.

PMID- 7716753
TI  - [Horse controls--animal welfare in equine sports].
AB  - In the course of ten horse-shows 248 horses were submitted to a short veterinary
      examination in the course of the horse controls that were introduced in 1991. In
      143 horses (57.6%) animal cruelty preventive deficiencies were found. The results
      of the horse controls are compared to previous results and discussed from the
      point of view of animal protection.

PMID- 7716754
TI  - [Embryo transfer in horses--current status and future perspectives].
AB  - Although foals born after embryo transfer are eligible for registration in the
      majority of horse breeds, application of embryo transfer is still rare. This is
      mainly due to the lack of a possibility for superovulation. Uterine stage embryos
      can be recovered by a non-surgical flushing technique. Transfer can be
      accomplished by non-surgical as well as surgical methods. In contrast to the
      situation in cattle, most related technologies are scarcely available. Methods of
      cryopreservation as well as bisection of embryos are hampered by the fact that
      suitable embryos (morula) can be collected from the uterus only during a very
      short period. In vitro production of embryos by in vitro maturation,
      fertilization and embryo culture is currently under investigation. Progress has
      been made to establish ultrasound-guided transvaginal oocyte aspiration. These
      techniques will provide an important stimulus for application of embryo transfer
      in equine species and enhance our knowledge about reproductive biology in the
      mare.

PMID- 7716755
TI  - [Diagnostic value of glutamate dehydrogenase determination in the dog].
AB  - Overproportional GLDH-increase was found to be the most frequently appearing
      pathological enzyme pattern in canine practice. Thus it could be shown that GLDH
      deviates, in spite of its mitochondrial localization and greater molecular
      weight, more frequently and to a higher degree from its reference value than the
      parameters ALT, AST, AP, GGT and Bilirubin. The results of the study suggest that
      the liberation of the enzyme is less determined by the intensity than by the
      intralobular target of the liver insult. Therefore an increase in GLDH-activity
      should no longer be interpreted as the result of severe liver damage. On the
      contrary, the enzyme appeared to be the most sensitive indicator for the
      diagnosis of primary and secondary hepatopathies. The phenomenon of isolated GLDH
      increase could be interpreted in almost every disease group as an appearance of
      the over-proportional increase and can therefore be understood as a serological
      expression of a slight, perivenous liver affection. Only with effusion patients
      the enzyme pattern should be regarded as an independent finding, because it has
      extrahepatic reasons. The induction of the enzyme in cases of diabetes mellitus
      is discussed.

PMID- 7716756
TI  - [Genetic basis of idiopathic epilepsy in the golden retriever].
AB  - The genetic aspect of idiopathic epilepsy in the Golden Retriever was examined.
      336 pedigrees of a population of normal and epileptic dogs from five different
      generations were statistically evaluated. Most patients showed generalized Grand
      mal seizures and the onset was within one to three years in 75% of the dogs. A
      significant sex predisposition for males was found. The increased manifestation
      of seizures in some subpopulations and the repeated occurrence in different
      families of the same sires revealed that there is a genetic basis for the
      condition of this breed. The results of pedigree analyses and binomial test
      support the hypothesis of an autosomal multifactorial recessive mode of
      inheritance. However, only an objective test-mating programme is likely to
      delineate the exact mode of inheritance.

PMID- 7716757
TI  - [Canine parvovirus: recent knowledge of the origin and development of a viral
      pathogen].
AB  - Canine parvovirus (CPV) is a "new" virus that suddenly emerged in the mid 1970s.
      Antigenetically it is very similar to the long known feline panleukopenia virus
      (FPV). Soon after its appearance CPV was classified as a mutant of FPV. As with
      all "new" viruses, CPV continues to show active evolution, obvious by the
      appearance of new antigenic types. Interestingly, the new types, designated CPV
      2a and CPV-2b, completely replaced the original type. This review summarizes the
      facts that are known about the emergence and evolution of CPV and discusses the
      relevance of the new antigenic types for the diagnosis of CPV and the vaccination
      against it.

PMID- 7716758
TI  - [Pets as patients in the small animal practice. 1. Descent, physiology,
      husbandry, feeding].
AB  - Small pets as domestic animals and patients in veterinary practice have gained in
      importance during the last years. Their different habits and needs require exact
      knowledge of their descent and physiology, as well as husbandry and feeding
      requirements. Therefore, a survey of rabbit, guinea-pig, chinchilla, hamster,
      gerbil, mouse and rat as pets is given.

PMID- 7716759
TI  - [Noninvasive patient observation in veterinary medicine: pulse oximetry and
      capnography. I. Pulse oximetry].
AB  - Two non-invasive continuous techniques for monitoring the respiratory function
      during anaesthesia have been established during the last year: pulse oximetry for
      monitoring the adequate oxygen supply and capnography for measuring the carbon
      dioxide elimination. In human medicine both are accepted as essential monitors
      with great reliability. Whether clinical use and interpretation can be
      transferred to animals without any restrictions will be discussed by looking on
      the physical and engineering background as well as the physiologic interpretation
      of the measured variable and their capability to detect critical events during
      administration of anaesthesia. Part I: Pulse oximetry measures the arterial
      oxygen saturation continuously and non-invasively. Its application in veterinary
      medicine must be discussed critically concerning the method as well as the
      interpretation. The information obtained is very different during injectable and
      inhalant anaesthesia. Respiratory depression is easy to detect while the animal
      breathes room air spontaneously. Is the inspired air enriched with oxygen, like
      during inhalant anaesthesia, normal values of oxygen saturation can mask the
      respiratory insufficiency and may give a false sense of security.

PMID- 7716760
TI  - Testing of metoclopramide and procainamide for their ability to induce genotoxic
      effects in cultured mammalian cells.
AB  - Metoclopramide (MCA) and procainamide (PCA), two widely used benzamide drugs
      developed before the present regulatory climate but recently found to induce DNA
      breaks in human lymphocytes, were evaluated for their genotoxic effects in
      cultured rodent and human cells. In subtoxic concentrations neither MCA (from
      0.10 to 0.32 mM) nor PCA (from 0.18 to 0.56 mM) induced DNA fragmentation and
      repair in primary cultures of metabolically competent rat and human hepatocytes.
      In the absence of metabolic activation a meaningful increase in the frequency of
      6-thioguanine-resistant V79 cells was produced by the maximum tolerated
      concentration of MCA (3.2 mM), whereas PCA resulted nonmutagenic. Any clastogenic
      effect was absent in human lymphocytes exposed to MCA for 28 hr, but a
      statistically significant increase in the frequency of micronucleated cells was
      observed when the exposure was prolonged to 72 hr. In contrast, PCA was never
      clastogenic under the same experimental conditions. These results suggest that of
      the two benzamides tested only MCA should be considered potentially capable of
      producing mutagenic and clastogenic effects; it presumably behaves as an agent
      which is rapidly transformed by the liver into inactive metabolites, and the
      clinical relevance of its genotoxic activity remains to be ascertained.

PMID- 7716761
TI  - Evaluation of DNA-damaging, clastogenic, and promoting activities of
      metoclopramide and procainamide in rats.
AB  - The DNA-damaging and clastogenic activities of metoclopramide (MCA) and
      procainamide (PCA), two substituted benzamides not systematically tested for
      genotoxicity before clinical use, were investigated in rats given a single high
      oral dose (500 mg/kg) of these drugs. Neither MCA nor PCA induced DNA
      fragmentation in liver, kidney, gastric mucosa, spleen, and bone marrow, as
      detected by the alkaline elution technique. Moreover, neither drug increased the
      frequency of micronucleated hepatocytes and the frequency of micronucleated
      polychromatic erythrocytes in the bone marrow of partially hepatectomized rats.
      However, in rats initiated with N-nitrosodiethylamine and given water containing
      0.125% MCA for 14 successive days a clear-cut and statistically significant
      increase in the number and size of liver gamma-glutamyltranspeptidase-positive
      foci and basophilic foci, which are consistent with potential promoting activity,
      was observed. Under the same experimental conditions the effect of PCA was
      markedly lower, only limited to a modest increase of the number and area of gamma
      glutamyltranspeptidase-positive foci.

PMID- 7716762
TI  - Neutrophil degranulation and superoxide production induced by polychlorinated
      biphenyls are calcium dependent.
AB  - 2,2',4,4'-Tetrachlorobiphenyl (TCB), a polychlorinated biphenyl (PCB), alters
      neutrophil functions in vitro by unknown mechanisms. The role of calcium in
      mediating PCB stimulation of neutrophil function was investigated. Peritoneal
      neutrophils were isolated from retired breeder, male, Sprague-Dawley rats.
      Neutrophils were incubated with 10 micrograms/ml 2,2',4,4'-TCB prior to
      stimulation with phorbol myristate acetate (PMA), and superoxide anion (O2-)
      production was measured. 2,2',4,4'-TCB alone elicited O2- production and
      potentiated the response to PMA. When neutrophils were incubated in calcium-free
      medium, the ability of TCB to stimulate O2- production and to potentiate the
      response to PMA was abolished. The absence of extracellular calcium did not alter
      the response to PMA alone. TMB-8, an antagonist of the mobilization of
      intracellular calcium, inhibited O2- production in response to 2,2',4,4'-TCB
      stimulation but not to PMA. Degranulation of neutrophils, measured by release of
      myeloperoxidase, occurred upon exposure to 10 micrograms/ml 2,2',4,4'-TCB alone.
      This response was increased by cotreatment with the calcium ionophore A23187.
      2,3,4,5-TCB, a mono-ortho-substituted PCB congener, potentiated O2- production in
      response to PMA stimulation by a mechanism that was partly dependent on the
      presence of extracellular calcium. This congener also stimulated neutrophils to
      release myeloperoxidase. 3,3',4,4'-TCB, a coplanar congener with high affinity
      for the Ah receptor, did not elicit neutrophil degranulation. These results
      indicate that TCBs affect neutrophil function in vitro through signal
      transduction pathways that appear to be calcium dependent.

PMID- 7716763
TI  - Effect of agents which modify reticuloendothelial system function on acute
      phalloidin-induced lethality and hepatotoxicity in mice.
AB  - The relationship between reticuloendothelial system (RES) function and acute
      phalloidin intoxication was studied in mice. Pretreatment with compounds that
      stimulate (zymosan) or depress (methyl palmitate and praseodymium nitrate,
      Pr(NO3)3) the RES resulted in protection against phalloidin-induced lethality and
      hepatotoxicity, as assessed by morphological analysis. However, triolein (which
      stimulates the RES) was ineffective against phalloidin. The timing of
      pretreatment with the effective compounds showed a correlation between modified
      in vivo RES function (phagocytosis) and protection against the toxin. The effects
      of pretreatment with zymosan and Pr(NO3)3 were further characterized. Hepatic
      damage induced by phalloidin was significantly decreased by these agents, as
      judged by morphological analysis as well as by serum aspartate aminotransferase
      and alanine aminotransferase release. This study also showed that there was no
      correlation between the capacity of Kupffer cells to produce nitrite and
      prophylaxis against phalloidin. However, liver cell proliferation was increased
      by zymosan and Pr(NO3)3 in parallel with protection against the toxin.
      Furthermore, freshly isolated hepatocytes from zymosan- or Pr(NO3)3-treated mice
      were less sensitive to phalloidin in vitro. These results indicate that the
      protective effect of these agents against phalloidin-induced hepatotoxicity may
      be mediated by their mitogenic properties.

PMID- 7716764
TI  - The hepatocarcinogen methapyrilene but not the analog pyrilamine induces
      sustained hepatocellular replication and protein alterations in F344 rats in a 13
      week feed study.
AB  - Methapyrilene (MPH) was a widely used antihistamine until it was found to produce
      hepatocellular carcinoma and cholangiocarcinoma in Fischer 344 rats. The
      structurally similar antihistamine pyrilamine (PYR) was marginally or
      noncarcinogenic in a similar study. The peroxisome proliferator Wy-14,643 was
      included in this study as a positive control. As part of a program to investigate
      the mechanisms whereby structurally similar chemicals produce different
      toxicities, we studied these three chemicals for the induction of cell
      proliferation in the liver of F344 rats. Male rats were treated for up to 13
      weeks with feed dosed with MPH (HCl salt) at 0, 50, 100, 250, or 1000 ppm or PYR
      (maleate salt) at 1000 ppm to duplicate the route of administration and high-dose
      groups used in the carcinogenesis assay. In addition, the nongenotoxic
      hepatocarcinogen peroxisome proliferator Wy-14,643 was included as a positive
      cell-proliferating chemical. Cell proliferation was quantitated by measuring the
      incorporation of bromodeoxyuridine (BrDU) administered by osmotic minipump for 7
      days and the appearance of proliferating cell nuclear antigen (PCNA)
      immunohistochemically. The BrDU-labeling index showed a large and sustained
      increase in rats treated with MPH at 250 and 1000 ppm, sustaining greater than
      50% labeling in the higher dose group of 4-, 6-, and 13-week treatment groups.
      PYR at 1000 ppm demonstrated no significant increase in labeling above control
      levels at any time point. PCNA-labeling indexes showed similar but reduced
      increases for MPH and were comparable to control for the PYR dose groups. Two
      dimensional gel electrophoresis was used for the detection of quantitative
      changes in gene expression and qualitative changes in the charges of specific
      mitochondrial and cytosolic proteins. Quantitative changes in 32 proteins induced
      by MPH and 39 changes induced by Wy-14,643 were detected throughout the 13-week
      study. Specific mitochondrial protein charge shifts were associated with high
      dose MPH treatment that were not observed in animals treated with Wy-14,643. PYR
      induced no significant qualitative or quantitative protein alterations.
      Hepatocellular proliferation of the large magnitude observed following dietary
      administration of MPH, and not PYR may contribute to the mechanism of
      carcinogenesis of MPH.

PMID- 7716765
TI  - In vitro glucuronidation of peroxisomal proliferators: 2-ethylhexanoic acid
      enantiomers and their structural analogs.
AB  - In order to investigate the glucuronidation of 2-ethylhexanoic acid (2-EHA), a
      metabolite of the plasticizer di-(2-ethylhexyl) adipate, by liver microsomes of
      several mammalian species including man, a gas chromatography method for the
      quantification of the corresponding glucuronides was developed. The variation
      coefficients for intra- and interassay repeatability were less than 3 and 7%,
      respectively. The rat liver UDP-glucuronosyl-transferase (UGT) presented similar
      Km and Vmax toward the two enantiomers. The glucuronidation of the racemate 2-EHA
      or its enantiomers was strongly increased up to six times by treatment of the
      rats with phenobarbital and, to a lesser extent, by 3-methylcholanthrene. In
      contrast, the treatment of the rats clofibrate did not modify the activity. The
      induction was not stereoselective. The Gunn rats, which present a genetic defect
      in the bilirubin UGT isoforms, were able to glucuronidate the drug as well as the
      congenic strain. Moreover, the UGT-2B1 isoform, stably expressed in V79 cells,
      glucuronidated 2-EHA in an appreciable amount. Interspecies comparison indicated
      that the most active glucuronidation of 2-EHA occurred in the dog and the rat.
      The lowest activities were observed in the man and the rabbit. In all species
      considered, except rabbit and guinea pig which glucuronidated the R isomer
      faster, the R and S enantiomers were glucuronidated to a similar extent. The
      glucuronidation activity toward compounds chemically related to 2-EHA increased
      as a function of molecular weight, but was not affected by the position of the
      methyl or the ethyl moiety on the hydrocarbon chain. A correlation between the
      glucuronidation rate of 2-EHA and analogs and the activity of PCoA oxidase was
      observed.

PMID- 7716767
TI  - Modeling of the toxicokinetics of polychlorinated dibenzo-p-dioxins and
      dibenzofurans in mammalians, including humans. I. Nonlinear distribution of
      PCDD/PCDF body burden between liver and adipose tissues.
AB  - Mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans, globally called
      PCDXs, are ubiquitously present in the environment. They accumulate in the human
      organism, especially through uptake from food. In view of their long residence
      time in the body and their potential adverse health effects for humans, it is
      therefore important to develop toxicokinetic models capable of predicting their
      distribution in human tissues. In the present study a physiologically based model
      which describes the distribution kinetics of PCDXs in various mammalian species
      is proposed. The approach is both theoretical and empirical. First, a plausible
      and general dynamical model that takes into account intercellular diffusion, PCDX
      receptor and PCDX-protein binding, and PCDX-dependent enzyme induction in the
      liver is developed. Simplified formulas are proposed to predict the functional
      dependencies fh(Cb) and f(at)(Cb), which establish the fractions of the total
      PCDX body burden contained in liver and adipose tissues as a function of overall
      body concentration at any one moment. These formulas have fewer free parameters
      that can be determined for various species with the use of already available
      data. Model simulations are in agreement with published data on the distribution
      kinetics of PCDXs in rodents and monkeys and clinical data in humans. In rodents
      and monkeys as well as in humans, the respective relations fh(Cb) and f(at)(Cb)
      follow a similar nonlinear pattern. These varying distribution functions
      constitute the basis for a generalized toxicokinetic model of absorption and
      disposition described in a companion article (G. Carrier, R. C. Brunet, and J.
      Brodeur, 1995, Toxicol. Appl. Pharmacol. 131, 267-276).

PMID- 7716766
TI  - Species-specific mechanism in rat Leydig cell tumorigenesis by procymidone.
AB  - To clarify the mechanism of species difference in the induction of testicular
      interstitial cell tumor (ICT, Leydig cell tumor) between rats and mice, male
      Sprague-Dawley rats and ICR mice were fed procymidone at dietary concentrations
      of 700, 2000 or 6000 ppm and 1000, 5000, or 10,000 ppm, respectively, for 3
      months. The Leydig cell functions were evaluated by serum testosterone and
      luteinizing hormone (LH) levels, testosterone levels in the testis, LH levels in
      the pituitary, the capacity of the testis to respond to gonadotropin stimulation,
      i.e., the production of testosterone in vitro, and by the testicular binding of
      labeled human chorionic gonadotropin (hCG). Measurement of testosterone and LH
      levels in rat serum, the testis, or the pituitary showed that both hormones were
      enhanced throughout the 3-month treatment period. The hypergonadotropism was
      associated with the increase of interstitial cell response to hCG in vitro for up
      to 3 months. As with rats, both serum and pituitary LH were increased in mice at
      4 weeks but not at 13 weeks. However, in contrast to rats, no significant
      increase in testosterone was observed in mice either in vivo or ex vivo during
      the course of the study. This suggests a difference between the rat and mouse in
      the response of the Leydig cell to the LH stimulation associated with procymidone
      administration. These differences in the response of interstitial cells to
      procymidone may be the basis for the distinct species responses to procymidone
      induced Leydig cell tumorigenesis. The sustained response of the Leydig cells to
      stimulation in the rat results in chronic hyperplasia and subsequent benign tumor
      formation, while the attenuated response of Leydig cells in the mouse is
      associated with neither hyperplasia nor neoplasia.

PMID- 7716768
TI  - Modeling of the toxicokinetics of polychlorinated dibenzo-p-dioxins and
      dibenzofurans in mammalians, including humans. II. Kinetics of absorption and
      disposition of PCDDs/PCDFs.
AB  - In the present study, a physiologically based model which describes the
      absorption and disposition kinetics of PCDDs/PCDFs (globally called PCDXs) in
      mammalian species, including humans, is developed. The model integrates the
      distribution model developed in the first article of this series, which described
      the fractional distribution of total PCDXs between liver and adipose tissues as a
      function of overall body concentration (G. Carrier, R. C. Brunet, and J. Brodeur,
      1995, Toxicol. Appl. Pharmacol. 131, 253-266). In particular it is shown that the
      liver fraction of the total body burden decreases as overall body concentration
      decreases. Since elimination is principally through the liver, this leads to
      lower global elimination rates and longer half-lives of PCDXs. Absorption and
      disposition kinetics of PCDXs are captured using nonlinear differential equations
      with anatomically and biochemically relevant input parameters which are readily
      available. These are solved to predict the fate of PCDXs in liver, adipose
      tissues, and the body as a whole, as a function of time. Model simulations are in
      agreement with published data on absorption and disposition kinetics of these
      substances in rats and in humans. The kinetic profiles are similar for rats and
      humans, but the varying half-lives differ considerably in both species: weeks
      with rats, years with humans. For a given body burden, the adipose tissue
      concentrations vary in an inversely proportional manner to the mass of the
      adipose tissues; this observation has considerable relevance for interpretation
      of clinical data for humans. The interest of the proposed model rests upon the
      fact that it is generalized and broadly applicable: it allows the study of the
      kinetics of PCDXs for any pattern of exposure from background to highly toxic
      levels, taking into account variations in time of anatomical and biochemical
      parameters.

PMID- 7716770
TI  - Physiologically based models for bone-seeking elements. V. Lead absorption and
      disposition in childhood.
AB  - A physiologically based model of lead absorption and disposition, previously
      developed and validated for adults, has been tested and calibrated for children.
      The model was modified to incorporate additional information on the age
      dependence of bone formation rate and to take into account increasing
      localization of bone modeling activity with age. A bone volume characterized by
      mature bone metabolic activity increases from zero at birth to the total bone
      volume by young adulthood. Bone formation rate is high from childhood through
      adolescence, with peaks at birth and around puberty. Bone resorption rate keeps
      pace at a rate that allows the orderly increase of bone mass. In general, the
      model reproduces childhood blood lead observations well, except in instances
      where lead is ingested at very high concentrations. Both bone and blood lead
      concentration are labile during early childhood because of the high rate of bone
      turnover. They respond rapidly to increases in lead exposure, and decrease almost
      as rapidly to near-preexposure concentrations when exposure returns to background
      levels. As the child grows, fractional bone formation and resorption rates
      decline and total bone lead turnover becomes more sluggish. From the time of peak
      bone mineralization rate in adolescence into early adulthood, the rate of bone
      turnover drops dramatically and the ability to reverse bone lead accumulation
      relatively rapidly is lost.

PMID- 7716769
TI  - Phenoxyl radicals of etoposide (VP-16) can directly oxidize intracellular thiols:
      protective versus damaging effects of phenolic antioxidants.
AB  - Phenolic compounds can act as radical scavengers due to their ability to donate a
      mobile hydrogen to peroxyl radicals producing a phenoxyl radical if the phenoxyl
      radical formed in the radical scavenging reaction efficiently interacts with
      vitally important biomolecules, then this interaction may result in cytotoxic
      effects rather than in antioxidant protection. In the present work we have chosen
      two model compounds--a phenolic antitumor drug, VP-16, known to be highly
      cytotoxic, and a homolog of vitamin E, 2,2,5,7,8-pentamethyl-6-hydroxychromane
      (PMC)--as typical representatives of phenoxyl radicals to study interactions of
      their phenoxyl radicals with intracellular thiols. Using a water-soluble source
      of peroxyl radicals, the azo-initiator 2,2'-azobis(2-aminodinopropane) (AAPH), we
      found that both PMC and VP-16 are very efficient scavengers of peroxyl radicals
      as evidenced by their ability to inhibit AAPH-induced chemiluminescence of
      luminol and oxidation of PnA incorporated into DOPC liposomes. Both PMC and VP-16
      were also able to protect against AAPH-induced oxidative degradation of DNA in
      nuclei from human leukemic K562 cells. In contrast, there was a dramatic
      difference in the ability of VP-16 and PMC to protect GSH against AAPH-induced
      oxidation: while PMC inhibited AAPH-induced oxidation of GSH in a concentration
      dependent manner, VP-16 did not protect GSH against oxidation. We hypothesized
      that this was due to different reactivities of the phenoxyl radicals formed by
      AAPH-derived peroxyl radicals from VP-16 and PMC toward GSH. To substantiate this
      hypothesis, we compared interactions of the phenoxyl radicals generated from VP
      16 and PMC with intracellular thiols in K562 cell homogenates. While the PMC
      phenoxyl radicals were only slightly affected by thiols, the VP-16 phenoxyl
      radicals were reduced by thiols. This is evidenced by (i) a significant
      inhibition of the tyrosinase-induced VP-16 consumption upon addition of K562 cell
      homogenates, (ii) a depletion of endogenous thiols in K562 cell homogenates
      induced by VP-16+tyrosinase, (iii) a transient disappearance of the VP-16
      phenoxyl radical signal from the ESR spectra and its reappearance after depletion
      of endogenous thiols, and (iv) elimination of the lag period for the appearance
      of the VP-16 phenoxyl radical ESR signal subsequent to depletion of thiols by
      mersalyl acid. To evaluate the contribution of GSH and protein thiols to
      reduction of the VP-GSH-peroxidase + cumeme hydroperoxide to specifically deplete
      endogenous GSH.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7716771
TI  - B lymphocyte precursor cells represent sensitive targets of T2 mycotoxin
      exposure.
AB  - Exposure of experimental animals and humans to the Fusarium trichothecene
      metabolite, T2 toxin, has been associated with a variety of immunosuppressive
      effects, including altered parameters of humoral-mediated immunity. Although T2
      toxin is cytotoxic in vitro to lymphocytic cells, limited information is
      presently available regarding the contribution of such a mechanism to
      immunosuppression in vivo, or to potential immune cell targets. In the present
      report, subchronic T2 toxin treatment of timed-pregnant B6C3F1 mice resulted in
      significant and selective depletion of fetal liver cells expressing low levels of
      surface CD44 and CD45 antigens, suggestive of possible lymphoid progenitor cell
      sensitivity to this agent. Evaluation of CD45R antigen expression in fetal liver
      supported such a hypothesis, demonstrating a significant reduction in fetal liver
      B lymphocytic cells in animals exposed to T2 toxin. Subsequent in vitro T2 toxin
      exposure of fetal liver cells enriched for prolymphocytes by differential density
      gradient centrifugation demonstrated the presence of a highly sensitive
      subpopulation of cells that was eliminated in a selective, and near-complete,
      manner by T2 toxin exposure. This sensitive cell population was observed to have
      light-scatter characteristics of CD45R+ B-lineage lymphocytes. Additional studies
      in adult mice demonstrated a reduction in CD44lo and CD45R+ bone marrow cells
      similar to that seen in fetal liver, indicating that T2 toxin may also target
      immature B lymphocytes in this hematopoietic compartment. Taken together, these
      data suggest that the precursors of B cells may represent, for unknown reasons,
      highly sensitive targets of T2 toxin exposure.

PMID- 7716772
TI  - Regional differences in the effects of mainstream cigarette smoke on stored
      mucosubstances and DNA synthesis in F344 rat nasal respiratory epithelium.
AB  - This study was designed to determine the effects of mainstream cigarette smoke
      (MCS) on stored intraepithelial mucosubstances (IM) and DNA synthesis within the
      nasal respiratory epithelium of F344 rats and whether such effects persist after
      cessation of exposure. Rats were exposed to filtered air or diluted MCS for 9
      days over a 2-week period. Two hours prior to termination rats were injected with
      bromodeoxyuridine (BrdU) to label cells synthesizing DNA 1 or 14 days after the
      last exposure. Sections of nasal tissue blocks taken from a region immediately
      posterior to the incisor teeth were processed for light microscopy and
      histochemically stained to detect acidic and neutral IM and immunochemically
      stained to detect BrdU-labeled cells. The nasal septum was divided into three
      measurement zones (dorsal, mid-, and ventral) for morphometric quantitation of
      the volume density of IM and the unit length labeling index (ULLI). MCS-exposed
      rats terminated 1 day after the last exposure had 270% more IM in the dorsal
      septum, 58% less IM in the midseptum (due to regions of squamous metaplasia), and
      amounts of IM in the ventral septum similar to controls. MCS-exposed rats
      sacrificed 14 days after exposure still had increased amounts of IM in the dorsal
      septal region, but no regions of squamous metaplasia or amounts of IM in the mid-
      and ventral septal regions that were different from air-exposed controls. MCS
      exposure resulted in a significant increase in the ULLI 1 day but not 14 days
      after exposure in the ventral and midseptal regions only. The results of this
      study indicate that MCS exposure induces transient alterations in the mucous
      producing apparatus in the rat anterior nasal cavity that are resolved following
      2 weeks of recovery. However, the type and magnitude of the initial epithelial
      responses are dependent on the intranasal location of the airway epithelium
      examined.

PMID- 7716773
TI  - Pulmonary responses to amiodarone in hamsters: comparison of intratracheal and
      oral administrations.
AB  - Amiodarone (AD) has been shown to produce a transient pulmonary fibrosis in
      hamsters after intratracheal (i.t.) instillation. The goal of this study was to
      examine bronchoalveolar lavage (BAL) parameters during the development of
      fibrosis after i.t. AD in hamsters and to examine the responses to oral AD in
      hamsters for comparison to responses to i.t. AD in an effort to explore the roles
      of inflammation, phospholipidosis, and lung drug burden in AD-induced pulmonary
      disease. Two i.t. instillations on Days 0 and 7 of AD in hamsters produced
      fibrosis as characterized by elevated lung hydroxyproline content and variable
      increases in lavage macrophage, neutrophil, and eosinophil number through Day 28.
      Intratracheal AD also increased the permeability of the alveolar-capillary
      barrier as evidenced by an increase in BAL fluid albumin only on Day 8. Pulmonary
      phospholipidosis was not induced by i.t. AD and only small amounts of AD and its
      metabolite desethyl-AD (dAD) were detected in lung tissue through Day 10 after
      instillation on Days 0 and 7. The repeated oral administration of AD did not
      result in pulmonary fibrosis during the 35-day course of this study. Oral AD did
      cause a sustained increase in BAL fluid neutrophil number; other BAL cells were
      only slightly affected. Oral AD did not increase BAL fluid albumin content but a
      prominent BAL cell phospholipidosis was noted. Measurement of AD and dAD in lung
      tissue demonstrated a substantial accumulation of drug and metabolite after oral
      treatment with AD. The results of this study indicate that lung drug burden,
      pulmonary phospholipidosis, and lung neutrophil influx are not crucial factors in
      the development of AD-induced pulmonary fibrosis in hamsters. This study supports
      the possible involvement of physical damage to the lung and/or pulmonary
      eosinophilia in the generation of AD-induced pulmonary fibrosis in hamsters.

PMID- 7716774
TI  - Nitrofurantoin-stimulated reactive oxygen species production and genotoxicity in
      digestive gland microsomes and cytosol of the common mussel (Mytilus edulis L.).
AB  - The ability of nitrofurantoin (NF) to produce reactive oxygen species (ROS) was
      investigated in subcellular fractions of digestive gland of the mussel Mytilus
      edulis in terms of oxygen consumption and the formation of superoxide anion
      radical (O2-) (measured as SOD-sensitive cytochrome c reduction or SOD-sensitive
      sensitive .OH production), H2O2 (effect of catalase), and hydroxyl radical (.OH)
      (iron/EDTA-mediated oxidation of KMBA to ethylene). Additionally, the genotoxic
      effects of NF were examined using the Salmonella typhimurium umu mutagenicity
      assay. Microsomal NAD(P)H-dependent oxygen consumption was stimulated by NF,
      leading to the formation of H2O2. Stimulation of microsomal O2- production by NF
      was evident for NADH but not NADPH, confirming redox cycling at least with the
      former coenzyme. No stimulation of O2- production was obvious for cytosolic
      fraction with either coenzyme. NF stimulated microsomal NAD(P)H-dependent .OH
      production; the rates of .OH production were greater for NADH than NADPH; and the
      .OH was indicated to be formed, at least in part, by an iron-catalyzed Haber
      Weiss reaction. A role was indicated for a free radical driven Fenton reaction in
      the NF-stimulated microsomal production of .OH from NADPH. The production of
      mutagenic species from NF was observed for cytosol but not for microsomes, and
      the former effects were greater for NADH than NADPH. Overall, the NAD(P)H
      dependent microsomal generation of ROS, and the lack of correlation of ROS
      production with mutagenicity, are considered indicative of the potential of
      digestive gland to metabolize NF by both one-electron and two-electron reductive
      pathways. From this and other studies, enhanced ROS production by NF and other
      redox cycling xenobiotics is indicated to be a widespread phenomenon in aquatic
      organisms and a potential mechanism of pollutant-mediated toxicity.

PMID- 7716775
TI  - Suppression of cytotoxic T lymphocyte activity by 2,3,7,8-tetrachlorodibenzo-p
      dioxin occurs in vivo, but not in vitro, and is independent of corticosterone
      elevation.
AB  - Previous studies have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a
      potent immunosuppressive compound. In our laboratory, TCDD and structurally
      related polychlorinated biphenyls (PCBs) have been shown to suppress alloantigen
      specific cytotoxic T lymphocyte (CTL) activity in C57B1/6 mice. PCB-induced CTL
      suppression occurs coincident with significant elevation of plasma glucocorticoid
      (GC) levels (> 500 ng/ml). Since GC elevation can cause immune suppression, this
      study was conducted to determine if TCDD-induced CTL suppression is correlated
      with elevation of plasma corticosterone (CS), the major GC in mice. Single oral
      doses of TCDD (2.5-40 micrograms/kg) induced a dose-dependent suppression of CTL
      activity with a calculated 50% immunosuppressive dose (ID50) occurring at 7.2
      micrograms/kg. When total lytic units (LU)/spleen were calculated, the ID50 was
      2.8 micrograms/kg. In contrast, plasma CS levels were not significantly altered
      at doses below 40 micrograms/kg. These data suggest that TCDD-induced CTL
      suppression is not dependent on CS elevation. The direct effect of TCDD on CTL
      generation was tested by adding TCDD at 10(-13)-10(-9) M to in vitro mixed
      lymphocyte-tumor cell (MLTC) cultures. No alteration of CTL activity was observed
      after 5 days of culture at any TCDD concentration. In contrast, CS alone
      significantly suppressed CTL activity in vitro. CS-induced CTL suppression in
      vitro was neither enhanced nor inhibited by the presence of TCDD. These results
      suggest that TCDD causes CTL suppression in vivo by a mechanism that does not
      involve CS.

PMID- 7716776
TI  - Adverse health effects of lead at low exposure levels: trends in the management
      of childhood lead poisoning.
AB  - An extensive database has provided a direct link between low-level lead exposure
      during early development and deficits in neurobehavioral-cognitive performance
      evident late in childhood through adolescence. These consistent studies have
      demonstrated the presence of a constellation of neurotoxic and other adverse
      effects of lead at blood lead (BPb) levels at least as low as 10 micrograms/dl).
      Federal agencies and advisory groups have redefined childhood lead poisoning as a
      BPb level of 10 micrograms/dl. Before discussing some of these studies in greater
      detail, the pervasiveness of this entirely preventable disease today in millions
      of American children must be recognized.

PMID- 7716777
TI  - In vitro and in vivo effects of lead on specific 3H-PN200-110 binding to
      dihydropyridine receptors in the frontal cortex of the mouse brain.
AB  - It is assumed that several neurotoxic substances interfere with neuronal calcium
      channels. Therefore, we studied the effects of the heavy metals, cadmium, copper,
      lead, manganese, and zinc on the L-type calcium channels in the mouse brain.
      Characterization of the calcium channels was carried out using binding studies on
      homogenates from the frontal cortex with the DHP (dihydropyridine)-derivative, 3H
      PN200-110, which binds with high affinity to the DHP-receptor inside the L-type
      calcium channel. Furthermore, the in vivo effects of lead on the DHP-receptors
      were investigated in perinatally exposed mice. In these animals, the analysis of
      saturation experiments with 3H-PN200-110 showed no changes in receptor density or
      ligand affinity due to the lead exposure. In vitro, 3H-PN200-110 binding is
      absolutely dependent on the presence of calcium. Divalent cations, such as
      magnesium or manganese, which normally block the physiological effects of
      calcium, also enhance DHP-receptor binding. Interestingly, ions such as lead,
      cadmium and copper stimulate 3H-PN200-110 binding at low concentrations (0.1-10
      microM), but inhibit binding at higher concentrations. In contrast, zinc blocked
      DHP-receptor binding at low concentrations (< 100 microM) without any stimulating
      effects. These results suggest that modulation of the L-type calcium channel by
      heavy metal cations is one possible mechanism by which the regulation of calcium
      homeostasis in neurons is altered.

PMID- 7716778
TI  - Acute oral toxicity in rats of 3,7-bis-(4-trifluoromethylphenyl)-1,5,3,7
      dioxadiazocane compared with 3,7-bis-(3-trifluoromethylphenyl)-1,5,3,7
      dioxadiazocane and N,N'-oxydimethylenebis(2-trifluoromethylaniline).
AB  - The acute oral toxicity of 3,7-bis-(4-trifluoromethylphenyl)-1,5,3,7
      dioxadiazocane (4-TFMPD) was compared with its 3-substituted isomer, 3,7-bis-(3
      trifluoromethylphenyl)-1,5,3,7-dioxadiazocane (3-TFMPD) and with N,N'
      oxydimethylenebis(2-trifluoromethylaniline) (N,N'-oxy-DM-bis (2-TFMA)). 4-TFMPD,
      3-TFMPD, N,N'-oxy-DM-bis (2-TFMA) and their precursors (4-trifluoromethylaniline
      (4-TFMA), 3-trifluoromethylaniline (3-TFMA) and 2-trifluoromethylaniline (2
      TFMA), respectively) were administered intragastrically to male Wistar rats at a
      dose of 0.12 mmol/kg body weight/day for three consecutive days and the resulting
      effects on haematological variables were determined. 4-TFMPD induced the highest
      methaemoglobinemia as compared with 3-TFMPD and N,N'-oxy-DM-bis (2-TFMA).
      Haemolytic anaemia with Heinz bodies, neutrophilia, lymphocytosis, enlargement of
      the spleen and enhanced production of granulocytes/macrophages from
      multipotential bone marrow cells (as determined by CFU-C test) were observed in
      animals treated with 4-TFMPD and 4-TFMA, whereas no such effects were observed in
      the other treatment groups. In conclusion, 4-substituted aniline derivatives
      exert special haematotoxicity on the red blood cells and induce leucocytosis,
      which differs from the effects of their 2- and 3-substituted congeners.

PMID- 7716779
TI  - Subchronic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and their
      reversibility in male Sprague-Dawley rats.
AB  - The hypothesis tested in this experiment is that effects of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) show identical dose-responses after subchronic
      as after acute exposure when the dose is corrected for toxicokinetics. Groups of
      male Sprague-Dawley (S-D) rats were administered orally a total dose of 0, 0.2,
      2.3, 11.5, 35, 70 or 115 micrograms/kg of TCDD over a period of 10 weeks at 4
      ml/kg of vehicle. Body weight was recorded weekly. One week after the last dose
      of TCDD one half of the rats was killed and tryptophan 2,3-dioxygenase (TdO), 7
      ethoxyresorufin-O-deethylase (EROD) and phosphoenolpyruvate carboxykinase (PEPCK)
      activities were measured in livers, whereas tryptophan and total T4 (TT4) were
      determined in serum. The results show that the dose-response for decreased TdO
      and PEPCK activity and elevated serum tryptophan levels are similar if not the
      same as the dose-response for subchronic retardation of body weight increase.
      They also demonstrate that the dose-responses for the induction of EROD activity
      and the reduction of serum TT4 occurred at much lower doses than those for
      decreased TdO and PEPCK activities or elevated tryptophan levels and mortality.
      After a 6-week recovery period, PEPCK and TdO activities in liver as well as
      tryptophan in serum returned to near control values, whereas EROD activity and
      serum TT4 still displayed a dose-dependent induction and reduction, respectively,
      albeit both shifted to the right in accordance with toxicokinetics. These data
      support the notion that subchronic dose-responses of TCDD are similar to acute
      dose-responses when corrected for toxicokinetics and that at least some TCDD
      induced effects are reversible also in accordance with toxicokinetics.

PMID- 7716780
TI  - Very early changes in pulmonary protein kinase C-alpha and calpain II contents
      following injection of butylated hydroxytoluene (BHT) into mice.
AB  - Butylated hydroxytoluene (BHT)-induced lung damage in mice is an excellent model
      system for studying mechanisms of chemically-induced, reversible alveolar injury.
      Changes in the pulmonary contents of protein kinase C (PKC) and the calcium
      dependent protease, calpain, were previously noted during the repair phase
      following BHT-induced pneumotoxicity. Calpain is believed to initiate PKC down
      regulation. PKC-alpha is the major PKC isozyme and calpain II the major calpain
      isozyme in mouse lung. We have now studied the time course of these enzymatic
      changes in detail. Pulmonary PKC-alpha concentrations decreased as early as 45
      min after an i.p. injection of 200 mg/kg BHT. Calpain II levels rose within the
      first 40 min after BHT injection, and then declined below control levels. The
      rapidity of these changes implies a role of these enzymes in mediating the onset
      of injury. Lung damage and repair, as estimated by measuring the lung weight/body
      weight ratio, is maximal 6 days after administration of this dose of BHT. The
      extent of the decreased PKC-alpha and calpain II concentrations at this time was
      linearly related to the estimated degree of injury based on increased lung
      weight. This correlation suggests the value of monitoring these enzymes as
      putative early biomarkers of alveolar injury.

PMID- 7716781
TI  - The utility of chelating agents as antidotes for nephrotoxicity of gold sodium
      thiomalate in adjuvant-arthritic rats.
AB  - The effects of 2,3-dimercaptopropane sulphonate (DMPS) and N-(2-mercapto-2
      methylpropanoyl)-L-cysteine (bucillamine) against the renal damage induced by
      gold sodium thiomalate (AuTM) in adjuvant-arthritic rats were studied. Arthritic
      rats induced by adjuvant using Mycobacterium butyricum were injected
      intraperitoneally with a chelating agent (0.6 mmol/kg) immediately after
      intramuscular injection of AuTM (0.066 mmol/kg) every other day for 21 days.
      Treatment with DMPS and bucillamine prevented increases in the urinary excretion
      of protein, aspartate aminotransferase, and glucose and blood urea nitrogen level
      after AuTM injection. AuTM prevented the increase in both adjuvant-injected and
      uninjected hind-feet volumes. The prevention of these inflamed lesions by AuTM
      was not affected by DMPS and bucillamine. These chelating agents decreased the
      gold concentration in the kidney and liver after AuTM administration, but did not
      affect the hepatic and renal concentrations of copper, zinc, iron, and calcium
      except the renal copper level after AuTM. These findings suggest that DMPS and
      bucillamine are very useful antidotes for gold toxicity.

PMID- 7716782
TI  - Cell death in rat and mouse embryos exposed to methanol in whole embryo culture.
AB  - Methanol induces developmental toxicity in rats and mice producing exencephaly,
      cleft palate, cervical skeletal defects, reduced body weight, and increased
      embryo/fetal death. Exposure to methanol in whole embryo culture also induces
      developmental retardation, dysmorphogenesis, and embryo lethality. In the present
      study, cultured rat and mouse embryos were exposed to methanol and subsequently
      observed for morphological effects and increased cell death using modified
      Feulgen staining which allowed nuclei throughout the embryo to be examined in
      situ. Growth and developmental scores were reduced by methanol in both rat and
      mouse embryos and the mouse embryos were affected at lower concentrations when
      compared to the rat. Methanol increased cell death in specific regions of both
      rat and mouse embryos, including the forebrain, the visceral arches, otic and
      optic placodes. These regions form derivatives which manifest morphological
      abnormalities following exposure in vivo. Methanol did not increase cell death in
      the neuroepithelium or neural folds and neural tube defects cannot be explained
      by excess cell death. The results of this study suggest that increased cell death
      in specific regions of the exposed embryos has a role in producing cranial
      malformations, abnormalities of the eye and ear, and cleft palate.

PMID- 7716783
TI  - Effect of chronic L-dopa administration on serum luteinizing hormone levels in
      male rats.
AB  - We examined whether the repeated oral administration with a high dose of L-3-(3,4
      dihydroxyphenyl)-alanine (L-DOPA) in 0.5% carboxymethyl cellulose increases serum
      luteinizing hormone (LH) levels in male rats. Serum LH levels were increased 4 h
      after a single administration of 1000 mg/kg L-DOPA to male rats, and returned to
      control levels within 8 h after administration. Four hours after a single
      administration, serum LH levels were significantly increased by L-DOPA at 1000
      mg/kg, but not at 20, 100 or 200 mg/kg. Decreases in body weight and relative
      weight of the prostate were observed after 7 and 14 days of administration of
      1000 mg/kg per day L-DOPA, but no changes were observed in weight of the testis,
      epididymis or seminal vesicle. The administration of L-DOPA at 500 or 1000 mg/kg
      per day for 7 or 14 days resulted in increased basal serum LH levels and
      decreased basal serum prolactin levels 24 h after the last administration. Serum
      testosterone levels tended to be higher in treated than in control rats. The
      levels of two metabolites of dopamine (DA), 3,4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA), in rats treated with 500 mg/kg per day
      tended to be slightly higher than those in control rats after 7 days of
      administration. Levels of DA, DOPAC and HVA were significantly increased after 7
      and 14 days of administration of 1000 mg/kg per day and after 14 days of
      administration of 5000 mg/kg per day. The level of norepinephrine, but not its
      metabolite 3-methoxy-4-hydroxyphenylglycol, was significantly increased after
      only 7 days of administration of 1000 mg/kg per day. No significant changes were
      observed in levels of 5-hydroxytryptamine or its metabolite 5-hydroxyindole-3
      acetic acid with administration of 500 or 1000 mg/kg per day. These findings
      suggest that a prolonged treatment with a high dose of L-DOPA in male rats
      induces release of LH from the pituitary, resulting in sustained elevation of LH
      levels in peripheral circulation.

PMID- 7716784
TI  - Changes in nocturnal pineal indoleamine metabolism in rats treated with parathion
      are prevented by beta-adrenergic antagonist administration.
AB  - Parathion, an organophosphorous insecticide, was previously shown to enhance the
      nighttime rise in pineal N-acetyltransferase (NAT) activity and serum melatonin
      levels. The purpose of the present study was to test whether parathion acts on
      the pineal gland by means of a beta-adrenergic receptor mechanism. Whereas
      parathion (total dose 6.5 mg/kg body wt over 6 days) by itself significantly
      augmented nocturnal pineal NAT activity and serum melatonin levels in otherwise
      untreated rats, the insecticide was ineffective in reference to this enzyme when
      it was given in conjunction with the beta-adrenergic receptor antagonist
      propranolol (20 mg/kg body wt, 1 h before lights off). The augmentation of NAT
      activity by parathion also caused significant reductions in pineal serotonin (5
      HT); again, this response was blocked by propranolol treatment. Neither pineal
      hydroxyindole-O-methyltransferase (HIOMT) activity nor pineal levels of 5
      hydroxytryptophan or hydroxyindole acetic acid (5-HIAA) were significantly
      changed as a result of either parathion or propranolol treatment. The results are
      consistent with the idea that parathion influences pineal 5-HT metabolism either
      at the level of the beta-adrenergic receptor or via the sympathetic innervation
      to the pineal gland.

PMID- 7716785
TI  - The dental amalgam mercury controversy--inorganic mercury and the CNS; genetic
      linkage of mercury and antibiotic resistances in intestinal bacteria.
AB  - Mercury (Hg) vapor exposure from dental amalgam has been demonstrated to exceed
      the sum of all other exposure sources. Therefore the effects of inorganic Hg
      exposure upon cell function in the brain and in the intestinal bacteria have
      recently been examined. In rats we demonstrate that ADP-ribosylation of tubulin
      and actin brain proteins is markedly inhibited, and that ionic Hg can thus alter
      a neurochemical reaction involved with maintaining neuron membrane structure. In
      monkeys we show that Hg, specifically from amalgam, will enrich the intestinal
      flora with Hg-resistant bacterial species which in turn also become resistant to
      antibiotics.

PMID- 7716787
TI  - Molecular mimicry in halothane hepatitis: biochemical and structural
      characterization of lipoylated autoantigens.
AB  - Exposure of human individuals to halothane causes, in about 20% of all cases, a
      mild transient form of hepatotoxicity. A small subset of exposed individuals,
      however, develops a potentially severe and life-threatening form of hepatic
      damage, coined halothane hepatitis. Halothane hepatitis is thought to have an
      immunological basis. Sera of afflicted individuals contain a wide variety of
      autoantibodies against hepatic proteins, in both trifluoroacetylated form (CF3CO
      proteins) and, at least in part, in native form. CF3CO-proteins are elicited in
      the course of oxidative biotransformation of halothane, and include the
      trifluoroacetylated forms of protein disulfide isomerase, microsomal
      carboxylesterase, calreticulin, ERp72, GRP 78, and ERp99. Current evidence
      suggests that CF3CO-proteins arise in all halothane-exposed individuals; however,
      the vast majority of individuals appear to immunochemically tolerate CF3CO
      proteins. The lack of immunological responsiveness of these individuals towards
      CF3CO-proteins might be due to tolerance, induced through the occurrence of
      structures in the repertoire of self-determinants, which immunochemically and
      structurally mimic CF3CO-proteins very closely. In fact, lipoic acid, the
      prosthetic group of the constitutively expressed E2 subunits of the family of
      mammalian 2-oxoacid dehydrogenase complexes and of protein X, was shown by
      immunochemical and molecular modelling analysis to be a perfect structural mimic
      of N6-trifluoroacetyl-L-lysine (CF3 CO-Lys), the major haptenic group of CF3CO
      proteins. As a consequence of molecular mimicry, autoantibodies in patients' sera
      not only recognize CF3CO-proteins, but also the E2 subunit proteins of the 2
      oxoacid dehydrogenase complexes and protein X, as autoantigens associated with
      halothane hepatitis. Furthermore, a fraction of patients with halothane hepatitis
      exhibit irregularities in the hepatic expression levels of these native, not
      trifluoroacetylated autoantigens. Collectively, these data suggest that molecular
      mimicry of CF3CO-Lys by lipoic acid, or the impairment thereof, might play a role
      in the susceptibility of individuals for the development of halothane hepatitis.

PMID- 7716786
TI  - Stimulative effects of lead on bone resorption in organ culture.
AB  - To clarify whether hypercalcemia after injection of Pb to rats is due to
      biological bone resorption or physicochemical mineral dissolution, the effect of
      lead (Pb) on release of previously incorporated 45Ca in organ culture was
      investigated. Pb at 50 microM and above stimulated the release of 45Ca and
      hydroxyproline (Hyp). Pb did not stimulate 45Ca release from the bones
      inactivated by freezing and thawing. Eel calcitonin (ECT), bafilomycin A1 and
      scopadulcic acid B (SDB) inhibited Pb-stimulated 45Ca release. These results
      indicate that Pb-induced 45Ca release is due to osteoclastic bone resorption. Pb
      stimulated bone resorption was inhibited by indomethacin and flurbiprofen. Pb
      stimulated the release of prostaglandin E2 (PGE2) from the bones into the media.
      There was significantly high correlation between 45Ca and PGE2 release. Pb
      induced bone resorption was inferred to be mediated by PGE2. From these results,
      it was suggested that hypercalcemia after Pb injection might be caused by
      biological bone resorption.

PMID- 7716788
TI  - Epitope mapping of beta-lactam antibiotics with the use of monoclonal antibodies.
AB  - In order to evaluate the antigenic contribution of different regions of the
      penicillin molecule, monoclonal antibodies were raised against amoxicillin
      protein conjugates and their specificities analysed in detail. A random sample of
      the clones produced was analysed by a quantitative inhibition-ELISA, using, as
      inhibitors, monomeric conjugates of the following antibiotics to butylamine (BA),
      amoxicillin (AX), ampicillin (AMP), benzylpenicillin (BP) and the nuclear part of
      these, 6-aminopenicillanic acid (6-APA); and different parts of the following
      molecules: N-(p-hydroxyphenyl)-glycine (PHPG), N-phenylglycine (NPG),
      phenylacetic acid (PA) and thiazolidine (TIAZ). The results showed that 92% of
      the antibodies recognized an epitope in which the side chain was a major
      constituent, although with variable contributions from other regions of the
      molecule. There was a high degree of crossreactivity with aminopenicillins, but
      low or absent crossreactivity with BP. None of the antibodies recognized the
      thiazolidine ring or the conjugated nuclear region of the penicillins. Finally,
      one antibody seemed to recognize, equally, all the different structures tested.
      The possible relevance of these results to penicillin allergy is discussed.

PMID- 7716789
TI  - Mobilization of heavy metals by newer, therapeutically useful chelating agents.
AB  - Four chelating agents that have been used most commonly for the treatment of
      humans intoxicated with lead, mercury, arsenic or other heavy metals and
      metalloids are reviewed as to their advantages, disadvantages, metabolism and
      specificity. Of these, CaNa2EDTA and dimercaprol (British anti-lewisite, BAL) are
      becoming outmoded and can be expected to be replaced by meso-2,3
      dimercaptosuccinic acid (DMSA, succimer) for treatment of lead intoxication and
      by the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS, Dimaval) for
      treating lead, mercury or arsenic intoxication. Meso-2,3-DMSA and DMPS are
      biotransformed differently in humans. More than 90% of the DMSA excreted in the
      urine is found in the form of a mixed disulfide in which each of the sulfur atoms
      of DMSA is in disulfide linkage with an L-cysteine molecule. After DMPS
      administration, however, acyclic and cyclic disulfides of DMPS are found in the
      urine. The Dimaval-mercury challenge test holds great promise as a diagnostic
      test for mercury exposure, especially for low level mercurialism. Urinary mercury
      after Dimaval challenge may be a better biomarker of low level mercurialism than
      unchallenged urinary mercury excretion.

PMID- 7716790
TI  - Heavy metals and the etiology of Parkinson's disease and other movement
      disorders.
AB  - Heavy metals, such as iron and manganese, are involved in neurologic disease.
      Most often these diseases are associated with abnormal environmental exposures or
      abnormal accumulations of heavy metals in the body. There is increasing
      recognition that heavy metals normally present in the body also may play a role
      in disease pathogenesis through free radical formation. When a part of the brain
      known as the basal ganglia is affected, movements become disordered. Parkinson's
      disease is one of the most common movement disorders and is related to
      destruction of neurons in the substantia nigra pars compacta (SNpc) of the basal
      ganglia. The combination of high concentration of iron and the neurotransmitter,
      dopamine, may contribute to the selective vulnerability of the SNpc. Dopamine can
      auto-oxidize to produce free radicals particularly in the presence of iron and
      other heavy metals.

PMID- 7716791
TI  - The effect of nickel compounds on immunophenotype and natural killer cell
      function of normal human lymphocytes.
AB  - In order to elucidate effects of nickel on human lymphocytes in vitro, peripheral
      blood mononuclear cells from normal donors were initially tested for viability in
      the presence of increasing concentrations of two selected nickel salts, sparingly
      soluble nickel subsulfide (Ni3S2), and promptly-soluble nickel sulfate (NiSO4).
      After establishing the toxicity profile, the cells were cultured for 24 h with
      each compound at three nontoxic concentrations, 0.01 mM, 0.02 mM, and 0.04 mM, to
      determine its effect on lymphocyte immunophenotype and function. Cells were also
      cultured in the presence of 0.01-0.04 mM magnesium acetate, Mg(CH3COO)2, while
      still other cell samples were subjected to a mixture of Mg(CH3COO)2 plus either
      Ni3S2 or NiSO4 at equimolar concentration. Following the culture, the
      immunophenotype of the cells was determined by indirect immunofluorescence, using
      monoclonal antibodies to major differentiation antigens of peripheral blood
      mononuclear cells, and their natural killer activity toward K562 target cells was
      measured. Both nickel salts were found to exert distinct effects on lymphocyte
      phenotype. Exposure of cells to Ni3S2 resulted in the decline of CD4 and natural
      killer cell populations. NiSO4 diminished the abundance of natural killer cells
      and, to a limited extent, also of CD4 cells. The nickel salts tested suppressed
      natural cytotoxicity of peripheral blood mononuclear cells, with Ni3S2 acting
      more strongly than NiSO4. The addition of Mg(CH3COO)2 to a nickel salt during in
      vitro culture abolished the above inhibitory effects. Nickel and magnesium salts
      did not affect CD3, CD8, CD20, and CD11a cell populations. The results indicate
      that nickel salts have deleterious effects on human peripheral blood mononuclear
      cells in short-term in vitro culture, but the magnitude of these effects varies,
      depending on the cell subsets.

PMID- 7716792
TI  - Mechanistic studies on the potentiation of carbon tetrachloride hepatotoxicity by
      methamphetamine.
AB  - Recent studies have shown that methamphetamine is capable of potentiating the
      hepatotoxicity of carbon tetrachloride in mice. In the present study, it was
      found that this potentiation is sensitive to changes in the timing of the
      methamphetamine dose relative to the administration of carbon tetrachloride.
      Potentiation of hepatotoxicity, measured using serum alanine aminotransferase
      (ALT) activity, was observed only if the dose of methamphetamine (15 mg/kg, i.p.)
      was given with, or 3 h after, the carbon tetrachloride dose (0.005 ml/kg, i.p.).
      No increase in carbon tetrachloride hepatotoxicity was evident when
      methamphetamine was administered 3 h before the carbon tetrachloride dose, or
      when given 6 or more hours after carbon tetrachloride. Increased covalent binding
      of carbon tetrachloride to proteins and lipids, shown previously to occur when
      methamphetamine and carbon tetrachloride are administered together, was not
      observed when methamphetamine was administered 3 h after the carbon tetrachloride
      dose and could not, therefore, account for the increased toxicity resulting from
      this treatment regimen. Pretreatment with the Kupffer cell inhibitor gadolinium
      chloride (10 mg/kg, i.v.) significantly diminished the potentiation of carbon
      tetrachloride hepatotoxicity by methamphetamine, suggesting that potentiation by
      methamphetamine involves, at least in part, a stimulation of Kupffer cells. Mice
      administered a methamphetamine pretreatment regimen known to induce behavioral
      sensitization displayed an enhanced potentiation of carbon tetrachloride
      hepatotoxicity, i.e. the extent of potentiation by methamphetamine was increased
      and the methamphetamine dose required for potentiation was diminished. Mice
      pretreated with a methamphetamine sensitization regimen were also found to be
      more responsive to the effects of morphine to enhance carbon tetrachloride
      hepatotoxicity. These observations suggest that there are important CNS, as well
      as hepatic, components in the potentiation of carbon tetrachloride-induced liver
      injury by methamphetamine and perhaps other drugs.

PMID- 7716794
TI  - The influence of nutritional deficiencies on gastrointestinal uptake of cadmium
      and cadmium-metallothionein in rats.
AB  - The intestinal uptake and tissue distribution of cadmium (Cd) were studied in
      control rats and those deficient in zinc (Zn), iron (Fe) or cysteine (SH) using
      an in situ model where an intestinal loop of 5 cm was incubated with CdCl2 or Cd
      MT (MT, metallothionein) for 30 and 60 min. The intestinal content of Cd after
      incubation with CdCl2 or Cd-MT was not affected by nutritional deficiencies, but
      the Cd uptake from CdCl2 was always higher than that from Cd-MT. However, both Fe
      and Zn deficiencies had a marked effect on distribution of Cd in liver, kidney
      and pancreas. After 30 min incubation in situ with CdCl2, Cd was deposited only
      in liver in control and SH deficient rats, while Cd was detected also in kidney
      and pancreas of both Fe and Zn deficient rats. After 60 min incubation with
      CdCl2, the deposition of Cd in the liver, kidney and pancreas of Fe deficient rat
      was significantly higher than that in the control. The deposition of Cd after Cd
      MT incubation in situ was mainly found in kidney, and nutritional deficiencies
      increased the tissue deposition of Cd from Cd-MT. Similarly, the renal deposition
      of Cd absorbed from CdCl2 was markedly increased in Fe deficient rats. These
      results suggest that the intestinal uptake mechanisms of Cd from CdCl2 and Cd-MT
      are different and nutritional deficiencies can markedly increase the deposition
      of Cd in the kidney, the critical organ in chronic cadmium exposure.

PMID- 7716793
TI  - Modification of lipoperoxidative effects of dichloroacetate and trichloroacetate
      is associated with peroxisome proliferation.
AB  - Pretreatment of male B6C3F1 mice with clofibric acid (CFA) or trichloroacetic
      acid (TCA) in the drinking water results in a marked decrease in the
      lipoperoxidative response as measured by the production of thiobarbituric acid
      reactive substances (TBARS) in mouse liver homogenates following acute dosing
      with TCA or dichloroacetic acid (DCA). Pretreatment with TCA or CFA also
      increased palmitoyl-CoA oxidase activity, microsomal 12-(omega) hydroxylation of
      lauric acid and expression of P450 4A isoforms. At the doses utilized, DCA
      pretreatment did not increase the level of P450 4A protein, or markers of
      peroxisome proliferation. However, DCA-pretreatment did result in enhanced levels
      of TBARS, following acute dosing with DCA, compared to controls. Pretreatment
      with DCA, TCA, or CFA did not alter p-nitrophenol hydroxylation (an assay
      specific for P450 2E1), and no increases in immunodetectable P450 2E1, 4A, 1A1/2,
      2B1/2 or 3A1 protein were observed. Assays from CFA- and TCA-pretreated mice
      suggest that the reduction in the TBARS response seen in TCA-pretreated animals
      results from activities associated with peroxisome proliferation. This might
      result from the induction of systems efficient in scavenging of peroxide
      intermediates or detoxification of aldehyde by-products of lipid peroxidation.

PMID- 7716795
TI  - Copper metabolism leading to and following acute hepatitis in LEC rats.
AB  - The accumulation process of copper (Cu) in the liver and the following metabolic
      disorder of Cu were examined in LEC rats, a mutant strain which accumulates Cu
      with age and shows spontaneous acute hepatitis and/or hepatoma. Cu concentration
      in the liver of female rats was approximately 220 micrograms/g liver at 2 weeks
      of age, decreased to 100 micrograms/g liver at 4-6 weeks, and then started to
      increase with age linearly to the highest concentration of 250 micrograms/g liver
      at 16 weeks. Although the Cu level expressed by concentration (microgram/g liver)
      decreased during weaning, it increased linearly with age when it was expressed by
      content (mg/liver), indicating a constant and preferential accumulation of Cu in
      the liver. Cu concentration stopped increasing at 16 weeks in the liver, followed
      by a sudden decrease to 1/2 the highest level. Biological markers (serum lactate
      dehydrogenase and glutamic-oxaloacetic transaminase activities) for liver damage
      started to increase, together with the appearance of signs of jaundice, when Cu
      attained the highest concentration. Distributions of Cu and zinc (Zn) in the
      supernatant fraction of the liver indicated that both metals were mostly
      distributed to metallothionein (MT) and, to a small extent, to superoxide
      dismutase on a gel filtration column throughout the course of the experiments.
      Serum Cu concentration started to increase in a form of ceruloplasmin, together
      with serum marker enzyme activities for liver damage. Cu concentration in the
      kidneys also started to increase after the increase of serum Cu. The results
      indicate that Cu accumulates in the form of MT in the liver of LEC rats to a
      maximum level of approximately 250 micrograms/g liver, and then decreases
      suddenly with the onset of acute hepatitis. The maximum level seems to be related
      to the capacity of MT synthesis, and acute hepatitis is assumed to occur when Cu
      accumulates beyond the capacity. Serum Cu started to increase, from the
      abnormally low level, when the metal accumulated beyond the capacity of MT
      synthesis in the liver, and it was partly reabsorbed by the kidneys and the rest
      was excreted into urine. Changes in iron and zinc levels were determined and
      discussed in relation to those of Cu.

PMID- 7716796
TI  - Effects of pharmacological interventions on emetine cardiotoxicity in isolated
      perfused rat hearts.
AB  - The cardiotoxicity of emetine continues to be a significant clinical problem. The
      purpose of this study was to investigate the effect of several mechanistic
      interventions, including ICRF-187, an iron-chelating agent which protects against
      doxorubicin toxicity, atropine, and fructose-1,6-bisphosphate (FBP) on the
      toxicity of emetine in our isolated, perfused rat heart model. The model includes
      functional, electrocardiographic, and biochemical determinations in the same
      preparation. Atropine and ICRF-187 had no effect on the time needed for emetine
      to induce ventricular asystole, while FBP significantly increased this time.
      Administration of 47 microM atropine, 300 microM FBP, or 1 mM FBP decreased the
      release of lactate dehydrogenase (LDH) into the coronary effluent, while ICRF-187
      had no effect. These pharmacological interventions variably changed the amplitude
      of the biphasic response of the coronary flow to emetine. Finally, FBP was very
      effective in slowing the rate of QRS-waveform degeneration in the perfused
      hearts. Emetine caused PR- and QRS-prolongation which was not altered by FBP.

PMID- 7716797
TI  - Taiwan's transition from high fertility to below-replacement levels.
AB  - This article compares the fertility experience of Taiwanese in the eight years
      since the total fertility rate reached 2.1 with that before fertility reached
      replacement levels. During the earlier period, two-thirds of the fertility
      decline resulted from falling marital fertility and one-third from higher age at
      marriage. The changing age distribution retarded this decline. Since 1983, the
      further decline to 1.7-1.8 has been entirely the result of the trend toward later
      marriage. Older age distributions now facilitate the decline. Births postponed by
      those marrying later make the conventional TFR misleading. Computation based on
      parity-progression ratios raise TFRs from 1.7 to 2.0, a number less alarming to
      policymakers. Contraceptive prevalence is at saturation levels in all major
      populations strata. The "KAP-GAP" has disappeared. What would have happened
      without Taiwan's effective family planning program is impossible to determine,
      but clearly, contraceptive services supplied by the program were the major
      proximate cause of Taiwan's fertility decline.

PMID- 7716798
TI  - Using parity-progression ratios to estimate the effect of female sterilization on
      fertility.
AB  - In this article, a new methodology that employs parity-progression ratios to
      estimate the effect of female sterilization on fertility is described, and
      results using data from Ecuador are compared to those obtained using a previously
      existing approach that classifies women by marital duration. The methods differ
      in how they disaggregate marital fertility and in the assumption they make about
      what the subsequent fertility of sterilized women would have been if they had not
      been sterilized. The analysis of the Ecuadoran data shows that the estimate of
      births averted by sterilization has diminished over time, even as sterilization
      prevalence has been increasing. This situation is attributed to a decline in the
      fertility of nonsterilized women resulting from increased use of reversible
      methods of contraception.

PMID- 7716799
TI  - Abortion in Vietnam: measurements, puzzles, and concerns.
AB  - This report summarizes current knowledge about abortion in Vietnam, drawing upon
      government statistics, survey data, and fieldwork undertaken by the author in
      Vietnam throughout 1993 and part of 1994. The official total abortion rate in
      Vietnam in 1992 was about 2.5 per woman, the highest in Asia and worrisome for a
      country with a still-high total fertility rate of 3.7 children per woman.
      Vietnamese provinces exhibited substantial variation in both the rate of abortion
      and the type of procedures performed. Among the hypotheses explored to explain
      Vietnam's high rate of abortion are the borrowing of family planning strategies
      from other poor socialist states where abortion is common; current antinatal
      population policies that interact with a lack of contraceptive alternatives; and
      a rise in pregnancies among young and unmarried women in the wake of recent free
      market reforms. Because family-size preferences are still declining, abortion
      rates may continue to increase unless the incidence of unwanted pregnancy can be
      reduced, a goal that Vietnamese population specialists are seeking to achieve.

PMID- 7716800
TI  - Women's and health-care providers' views of maternal practices and services in
      rural Nigeria.
AB  - Maternal mortality and morbidity estimates in Nigeria continue to be dramatically
      high largely because maternal services, especially in rural areas, are often
      deficient and inappropriate to women's situations. The Safe Motherhood Project in
      Zone A examined the pregnancy-related knowledge, attitudes, and practices of
      community members, and women's use of community maternal health services. Focus
      group discussions and interviews confirmed a number of recent findings by other
      studies; they also documented extensive hostility between the two most commonly
      used health-care providers: traditional birth attendants and midwives. The
      hostility resulted in rumors, deliberate attempts to discourage women from
      seeking higher levels of care, and refusals to accept referrals or treat
      patients, which were found to be serious constraints to good maternal care in the
      targeted rural area.

PMID- 7716801
TI  - Should the recommended number of IUD revisits be reduced?
AB  - This study uses data from clinical trials of intrauterine devices to examine the
      effect of reducing the recommended number of IUD follow-up visits. Over 11,000
      follow-up forms were analyzed to estimate the number of health problems that
      would have escaped detection if women with no or mild symptoms had not made
      recommended revisits. Less than one percent of woman-visits with no or only mild
      symptoms had an underlying health risk that could have gone undetected if the
      follow-up visits that were made in the clinic trial setting had not been made.
      The results from this analysis suggest that a reduction in the number of
      recommended follow-up visits is safe, when measured according to selected
      conditions. Additional research is necessary to determine whether any revisits
      should be recommended in the absence of signs or symptoms.

PMID- 7716803
TI  - Glycogen synthase kinase and Dictyostelium development: old pathways pointing in
      new directions?

PMID- 7716802
TI  - Yemen 1991/92: results from the Demographic and Maternal and Child Health Survey.

PMID- 7716804
TI  - A rapid and efficient alternative to sonication in shot-gun sequencing projects.

PMID- 7716805
TI  - Pulsed-field gel electrophoresis of mosquito DNA.

PMID- 7716806
TI  - DNA extraction from urea-preserved blood or blood clots for use in PCR.

PMID- 7716807
TI  - A graphic digital database of Drosophila embryogenesis.
AB  - Modern studies of the genetic control of development have increased the need for
      an accurate and comprehensive storage and display of gene expression data. This
      can be achieved in the form of an electronic graphic database of development.
      Here, we introduce the first steps towards a database of Drosophila
      embryogenesis. For each morphologically defined stage, a complete series of
      histological and/or optical sections are generated (optical sections are
      generated by laser confocal microscopy). Digitized sections are imported into a
      drawing program where they serve as templates to define the contours of organs
      and the position of individual cells. From these data, surface and point cloud
      models of all developmental stages are generated. Gene expression data can be
      entered by translating the expression domain of a given gene into the three
      dimensional coordinate system of the database.

PMID- 7716808
TI  - The unusual telomeres of Drosophila.
AB  - The telomeres of most eukaryotes contain short, simple repeats that are highly
      conserved. Drosophila, on the other hand, does not have such sequences, but
      carries at the ends of its chromosomes one or more LINE-like retrotransposable
      elements. Instead of elongation by telomerase, incomplete DNA replication at the
      termini of Drosophila chromosomes is counterbalanced by transposition of these
      elements at high frequency specifically to the termini. These transposable
      elements are not responsible for distinguishing telomeric ends in Drosophila from
      broken chromosome ends; the structure performing this function is not yet known.
      Proximal to the terminal array of transposable elements are regions of tandem
      repeats that are structurally, and probably functionally, analogous to the
      subterminal regions in other eukaryotes.

PMID- 7716809
TI  - Chromosome landing: a paradigm for map-based gene cloning in plants with large
      genomes.
AB  - The original concept behind map-based or positional cloning was to find a DNA
      marker linked to a gene of interest, and then to 'walk' to the gene via
      overlapping clones (e.g. cosmids or YACs). While chromosome walking is
      straightforward in organisms with small genomes, it is difficult to apply in most
      plant species, which typically have large, complex genomes. The strategy of
      chromosome walking is based on the assumption that it is difficult and time
      consuming to find DNA markers that are physically close to a gene of interest.
      Recent technological developments invalidate this assumption for many species. As
      a result, the mapping paradigm has now changed such that one first isolates one
      or more DNA marker(s) at a physical distance from the targeted gene that is less
      than the average insert size of the genomic library being used for clone
      isolation. The DNA marker is then used to screen the library and isolate (or
      'land' on) the clone containing the gene, without any need for chromosome walking
      and its associated problems. Chromosome landing, together with the technology
      that has made it possible, is likely to become the main strategy by which map
      based cloning is applied to isolate both major genes and genes underlying
      quantitative traits in plant species.

PMID- 7716810
TI  - Jaks and Stats in signaling by the cytokine receptor superfamily.
AB  - Many cytokines mediate their biological effects through interaction with a
      distinct family of receptors termed the cytokine receptor superfamily. Although
      members of this family lack catalytic domains, they couple ligand binding to
      tyrosine phosphorylation. Recent studies have shown that a novel family of
      cytoplasmic protein tyrosine kinases, termed the Janus kinases (Jaks), associate
      with the cytokine receptors and are catalytically activated after ligand binding.
      The activated Jaks phosphorylate and activate members of a novel family of
      transcription factors termed signal transducers and activators of transcription
      (Stats). In addition, many cytokines induce the phosphorylation of SHC, Vav and
      the p85 subunit of PI-3 kinase. The region of the receptors proximal to the
      cytoplasmic membrane is required for Jak association, mitogenesis, Stat
      activation and Vav phosphorylation. The membrane-distal region, which contains
      the major sites of tyrosine phosphorylation, is required for phosphorylation of
      SHC and p85, not for mitogenesis, thus allowing functional dissection of the
      signaling pathways activated by cytokines.

PMID- 7716811
TI  - [Evaluation of cardiovascular risk in anesthesia. Role of the cardiologist].

PMID- 7716812
TI  - [Pulmonary-renal syndromes].

PMID- 7716813
TI  - [Fractures of the pelvic girdle: anatomic lesions and prognosis. 33 cases].

PMID- 7716814
TI  - [Incidence of toxoplasmosis during pregnancy and risk of fetal infection].

PMID- 7716815
TI  - [Value of cytology in the pathology of cervical and vaginal infections].

PMID- 7716816
TI  - [CT diagnosis of perceptive deafness: 42 cases].

PMID- 7716817
TI  - [Value of microalbuminuria determination in the non-insulin-dependent diabetic].

PMID- 7716818
TI  - [Cystic fibrosis mutations in the Tunisian population].

PMID- 7716820
TI  - [Struma ovarii: three case reports].

PMID- 7716819
TI  - [Primary hyperaldosteronism. Analysis of 5 cases of Conn's syndrome].

PMID- 7716821
TI  - [Sigmoid migration of an intrauterine contraceptive device: a case report].

PMID- 7716822
TI  - Expression of an endogenous retrovirus (ERV3 HERV-R) in human reproductive and
      embryonic tissues--evidence for a function for envelope gene products.
AB  - ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm
      of chromosome 7. It is expressed in several human tissues as LTR env spliced
      transcripts (9 and 3.5 kb). The highest level of expression is to be found in
      placenta and virus expression is down-regulated in choriocarcinoma cell lines. By
      means of in situ hybridization, the expression of ERV3 env was studied in
      selected human reproductive and embryonic tissues. It is concluded that (a) ERV3
      env is expressed in syncytiotrophoblasts not only in the placenta but also in
      hydatidiform moles and choriocarcinomas (irrespective of origin) (b) ERV3
      expression in placenta correlates to cell fusion but probably not to the
      fertilization process itself (c) ERV3 env is highly expressed in certain cells in
      spermatogenesis but not in the Sertoli or Leydig cells, and finally (d) ERV3 env
      is expressed in certain embryonic tissues such as the adrenal gland and nervous
      tissues.

PMID- 7716823
TI  - Inhibition of fibrinogen binding to platelets by MK-852, a new GPIIb/IIIa
      antagonist.
AB  - MK-852 is a newly developed low molecular weight inhibitor of fibrinogen binding
      to platelets. Platelet aggregation and adhesion of platelets to damaged vessel
      walls are critical events in haemostasis, and uncontrolled aggregation may cause
      arterial thrombus formation. Depending on the location of the occluded vessel,
      this may result in unstable angina, myocardial infarction or stroke. Platelet
      aggregation requires binding of fibrinogen to the GPIIb/IIIa receptor on the
      platelet surface. Thus, inhibitors of fibrinogen binding to the receptor may
      constitute an efficient way of preventing thrombus formation. We have used flow
      cytometry and FITC-labelled chicken anti-human fibrinogen antibodies to study the
      in vitro inhibitory effects of MK-852 on fibrinogen binding to platelets. We show
      that MK-852 is a very efficient fibrinogen receptor antagonist in vitro. Flow
      cytometry is well suited for clinical use and may be used to monitor treatment
      with MK-852 or other fibrinogen receptor antagonists.

PMID- 7716824
TI  - Antiaggregative therapy with acetylsalicylic acid and diclofenac in patients with
      acute myocardial infarction.
AB  - A total of 109 male patients with acute transmural myocardial infarction (MI)
      were studied. 26 patients received a dose of acetylsalicylic acid (aspirin, ASA)
      500 mg/d and 29 patients of 50 mg/d. 27 patients were given diclofenac (25 mg/d).
      27 patients received no antiplatelet therapy. We observed thrombocyte
      hyperaggregation on the 1st MI day, a rapid increase in platelet activity by the
      7th day and a considerable decrease in platelet aggregation during the 3rd and
      4th weeks of illness in the group without antiaggregative treatment. The present
      study clearly demonstrated high antiaggregatory efficacy of ASA in dose of 50
      mg/d which was significantly higher than that in daily dose of 500 mg ASA. Low
      dose aspirin had fewer side-effects than aspirin 500 mg/d. However, although
      daily dose of 50 mg aspirin significantly inhibited platelet hyperaggregation on
      7th day of MI, the hyperactivity of thrombocytes was not abolished. Diclofenac 25
      mg daily had only a moderate antiaggregative efficacy in acute MI patients.

PMID- 7716825
TI  - Washout kinetics of blood cells from the perfused pancreas of normoglycemic and
      diabetic rats.
AB  - The aim of the present study was to evaluate vascular compartments within the rat
      pancreas with compartmental analysis of the outflow of blood cells from the
      perfused gland in situ. The presence of two vascular compartments requiring
      approximately 15 and 30 min for emptying, was noted in normoglycemic rats. The
      pancreas from diabetic rats, in which the islet beta-cells had been destroyed by
      intravenous injection of streptozotocin 1 or 6 weeks earlier, demonstrated the
      same outflow characteristics. It is therefore likely that these observations
      reflect the presence of two vascular compartments within the rat pancreas,
      possibly representing the islet-acinar vasculature and the ductal vasculature.

PMID- 7716826
TI  - Decreased serum insulin-like growth factor I during puberty in children with
      insulin dependent diabetes mellitus (IDDM).
AB  - Previous reports concerning insulin-like growth factor-I (IGF-I) in diabetics are
      conflicting. This study describes IGF-I in children with insulin-dependent
      diabetes mellitus (IDDM) and healthy controls in relation to pubertal
      development. Sixty-six children participated (34 girls and 32 boys) of which 33
      had IDDM. The mean age in the study population was 14.3 years, (range 7.1 to
      19.7). Serum IGF-I was significantly decreased in diabetics. Diabetic girls had a
      mean IGF-I of 28.3 (14.4; = SD) nmol/l compared with 42.8 (15.0) nmol/l in
      controls. In diabetic boys the result was 30.0 (16.0) nmol/l compared with 44.1
      (23.4) in controls. Growth hormone was measured in only one fasting morning serum
      sample from each individual. There was no difference between girls, but diabetic
      boys had higher mean serum concentration of growth hormone than controls (3.5
      (4.8) vs. 1.8 (1.5) micrograms/l respectively). Diabetic girls had delayed
      menarche, corresponding to a slightly delayed bone maturation.

PMID- 7716827
TI  - The contemporary development of parathyroid surgery--an expose from an Uppsalian
      perspective.

PMID- 7716828
TI  - The incidence of neonatal pneumococcal septicemia in Sweden 1991-92. The result
      of a national survey.
AB  - In a survey of the incidence of pneumococcal neonatal septicemia in Sweden 1991
      92, to our knowledge the first nationwide survey of this kind, an incidence of
      3.6/100,000 was found. Based on this, the relative incidence of neonatal
      septicemia caused by pneumococci was calculated to be 0.9-1.3%. Despite recent
      reports of pneumococci resistant to antibiotics, no resistant strain was found,
      and among the affected neonates, all treated with conventional antibiotics, there
      was a lower mortality as compared to prior reports. This might reflect the facts
      that the infants were less often born preterm, were less often born after
      premature rupture of membranes, and had a higher proportion with a late onset of
      symptoms than in earlier surveys.

PMID- 7716829
TI  - The effect of peep-ventilation on cardiac function in closed chest pigs.
AB  - OBJECTIVE: Does ventilation with positive end-expiratory pressure (PEEP) depress
      myocardial contractility? DESIGN: Ten piglets were anaesthetized and prepared for
      the measurement of cardiac output (SV) and right (MRAPtm) and left (MLAPtm) mean
      transmural atrial pressure, the latter serving as indices of preload. 500 ml of
      autologous blood was re-transfused during intermittent positive pressure
      ventilation without PEEP (IPPV) and continuous positive pressure ventilation with
      15 cm H2O PEEP (CPPV). MEASUREMENTS AND RESULTS: Right and left ventricular
      function curves were drawn by plotting MRAPtm and MLAPtm respectively versus the
      corresponding strokevolumes before and after re-transfusion. Similar inclinations
      were obtained during IPPV and CPPV on either side of the heart. CONCLUSIONS:
      Although the ventricular function curves during IPPV and CPPV covered partially
      different preload levels, the results suggest that CPPV i.e. PEEP does not affect
      myocardial contractility.

PMID- 7716830
TI  - Kinetic measurement of the erythrocyte sedimentation rate.
AB  - A method for estimation of the erythrocyte sedimentation from repeated
      measurements during the initial part of the sedimentation phase is described.
      Based on the measurements between 18 and 24 minutes after the beginning of the
      reaction, the sedimentation at 60 minutes is estimated. The estimate is highly
      correlated to the measured ESR in the range which the conventional ESR permits
      (up to about 90 mm). Higher ESR will be estimated from the kinetic data and thus
      give reproducible and meaningful results of samples which will be reported as
      "falsely low" by conventional methods. Sedimentations of several hundred mm can
      thus be estimated suggesting a new use for the ESR, particularly in monitoring
      patients with severe inflammatory reactions.

PMID- 7716831
TI  - Use of a novel measuring technique for the erythrocyte sedimentation rate--a
      pilot study in patients with neutropenia and fever.
AB  - In the present study a new technique for measuring the erythrocyte sedimentation
      rate (ESR) is clinically evaluated. This technique extends the measuring range
      above that of the traditional ESR by calculating the sedimentation (S) at 60
      minutes from data collected between 18 and 24 minutes. Measurement of ESR, S and
      C-reactive protein (CRP) was performed prospectively three times a week in 25
      patients developing 30 fever episodes following chemotherapy for a hematological
      malignancy. A good correlation was obtained between S and ESR values up to 90 mm
      (r = 0.98; p < 0.0001). The use of S may allow the clinician to follow an
      infectious or inflammatory process more accurately than with ESR. During
      neutropenia a rise in S preceded fever in all episodes were two samples were
      obtained before start of fever (n = 13). Changes in CRP and S values showed the
      same pattern in 11 episodes, in 12 CRP preceded S and in 7 episodes there was no
      correlation between the results. CRP, opposed to S, discriminated between
      bacteremias and blood culture negative episodes (p < 0.05) in samples obtained
      during the first 72 hours after start of fever. In patients with fever during
      neutropenia determination of S does not offer any clear advantage to CRP.

PMID- 7716832
TI  - Functional and biochemical characteristics of human prostasomes. Minireview based
      on a doctoral thesis.

PMID- 7716833
TI  - William Hollis Cooner, M.D., F.A.C.S. 1927-1994.

PMID- 7716834
TI  - Practical clinical utility of DNA ploidy for managing patients with prostate
      carcinoma.

PMID- 7716835
TI  - DNA ploidy status.

PMID- 7716836
TI  - Renal cell carcinoma: considerations for nephron-sparing surgery.
AB  - OBJECTIVES: The performance of nephron-sparing surgery in patients with a
      normally functioning contralateral kidney is controversial. To explore the risk
      factors that may contribute to the success or failure of nephron-sparing surgery,
      we examined the radiology and pathology reports of 278 patients who underwent
      radical nephrectomy for the treatment of clinically localized renal cell
      carcinoma. METHODS: We collated patient data from the records of 278 patients
      with Stage III renal cell carcinoma entered into the Eastern Cooperative Oncology
      Group protocol EST 2886 and compared preoperative clinical staging with
      postoperative pathologic results. Patients were considered potential candidates
      for nephron-sparing surgery if their preoperative radiographic studies indicated
      that the carcinoma was a single polar lesion 5 cm or less in diameter. RESULTS:
      Of 278 radical nephrectomy specimens, 36 had primary lesions 5 cm or less in
      diameter. Preoperative radiographic studies showed 14 of 36 would not have been
      considered eligible for nephron-sparing surgery. Of the remaining 22 potential
      candidates, pathologic studies showed multifocal lesions in 11, renal vein
      disease in 4, and nodal disease in 2. Only 5 of 22 patients might have had
      specimen-confined disease (T3a lesion). CONCLUSIONS: Capsular-penetrating (T3a)
      renal cell carcinoma is not often appreciated preoperatively and is associated
      frequently with multifocal lesions, renal vein or nodal disease. Frozen section
      studies to rule out T3a disease at the time of nephron-sparing surgery may help
      determine which patients need radical surgery.

PMID- 7716837
TI  - Paraureteral calculi caused by ureteroscopic perforation.
AB  - OBJECTIVES: Ureteroscopy has become an effective and safe procedure for treatment
      of ureteral calculi. Formation of strictures are considered long-term
      complications with a low incidence. This report focuses on the incidence of
      strictures in cases of calculi pushed or flushed retroperitoneally alongside the
      ureter because of iatrogenic ureteral perforation. METHODS: Fifteen consecutive
      patients with paraureteral calculi caused by ureteroscopic perforation were
      observed. An excretory urogram was performed after a mean of 22.5 months, with a
      range of 9 to 54 months. In all patients, a stent was placed for 3 to 41 days
      (mean, 13.5 days) and antibiotics were administered between 3 and 5 days
      postoperatively. RESULTS: Only 1 patient of 15 with a short stricture of the
      distal ureter was observed. The stricture was successfully treated by endoscopic
      ureterotomy, balloon dilation, and transient placement of a ureteral stent.
      CONCLUSIONS: Paraureteral calculi caused by ureteral perforation are a minor
      complication of ureteroscopy, which rarely lead to formation of strictures.
      Removal of paraureteral calculi by enhanced endoscopic procedures or open surgery
      is not required.

PMID- 7716838
TI  - Risk factors in carcinoma in situ of the urinary bladder. Dutch South East
      Cooperative Urological Group.
AB  - OBJECTIVES: In this article we describe the long-term follow-up of patients with
      carcinoma in situ (CIS) of the urinary bladder and examine whether the extent of
      CIS, the presence of associated papillary tumors, or the response to treatment
      influence the course of the disease. METHODS: Fifty-two patients with CIS of the
      bladder, treated in a randomized prospective study, are described. In 23 patients
      with concomitant papillary tumors all macroscopically visible lesions were
      completely resected transurethrally (TUR). CIS was histologically confirmed in
      all patients by biopsy, 29 of whom had primary CIS. The patients were treated
      with intravesical mitomycin, bacille Calmette-Guerin (BCG)-RIVM or BCG-Tice and
      followed regularly by urine cytology, cystoscopy, and biopsy. RESULTS: Complete
      response was achieved in 65% of the patients. Of these responders, 24% later had
      a recurrence of CIS or a superficial tumor and 18% had progressive disease (PD).
      In the nonresponding patients, progression occurred in 67%. In the whole group,
      PD was seen in 35% of the patients, and radical cystectomy was performed in 21%.
      The disease-related death rate was 13%. The risk for recurrence or PD was not
      higher in patients with more extensive CIS, defined as three or more positive
      biopsy results or when CIS was associated with papillary tumors compared to
      patients with one or two biopsy specimens positive for CIS or CIS alone.
      Nonresponding patients showed a significantly higher progression rate and
      cystectomy rate than responding patients (P = 0.0012 and 0.008, respectively).
      CONCLUSIONS: CIS of the bladder is a malignancy with a poor prognosis, especially
      in patients not responding after intravesical treatment. Early detection and
      adjuvant intravesical treatment after TUR of concomitant papillary tumors are
      required. In patients not responding after intravesical treatment, radical
      surgery is necessary before progression occurs. The number of biopsies positive
      for CIS, not the presence of concomitant superficial tumors, was an indicator for
      progression or recurrence.

PMID- 7716839
TI  - Prostatodynia and interstitial cystitis: one and the same?
AB  - OBJECTIVES: To investigate further the observation that men with prostatodynia
      may represent a subset of patients with interstitial cystitis. METHODS: The
      charts of 20 patients with the diagnosis of nonbacterial prostatitis or
      prostatodynia who underwent cystoscopy and bladder hydrodistention were
      retrospectively reviewed. RESULTS: The primary complaint of all 20 patients was
      genital or rectal pain, or both. Ten patients reported irritative voiding
      symptoms. Twelve of the 20 patients developed petechial hemorrhages involving the
      bladder uroepithelium on hydrodistention. Bladder biopsies revealed no
      significant histopathologic abnormalities. Nine of the 12 patients who developed
      petechial hemorrhages reported symptomatic improvement at 2- to 3-week follow-ups
      compared with none of the 8 patients without petechial hemorrhages. CONCLUSIONS:
      These findings suggest that the diagnosis of interstitial cystitis should be
      considered in patients with nonbacterial prostatitis or prostatodynia.

PMID- 7716840
TI  - Computer simulation of the probability of detecting low volume carcinoma of the
      prostate with six random systematic core biopsies.
AB  - OBJECTIVES: Six random systematic core biopsies (SRSCB) of the prostate (biopsies
      from apex, middle, and base of each lobe) have been commonly used in detection of
      prostate carcinoma. The objective of this study was to verify the validity of the
      SRSCB technique in detecting cancer in prostates with low-volume tumor (less than
      6 cc). METHODS: We developed a computer model of the prostate to simulate the
      SRSCB technique. The data for development of this model were taken from 159
      radical prostatectomy specimens in which 112 patients had tumor volumes measured
      and in which 91 prostates had tumors with volumes less than 6 cc (by whole-mount
      sectioning). RESULTS: The simulation shows that only 20.3% of the simulated
      prostates, with total aggregate tumor volume between 0.034 and 5.1 cc, had a
      tumor distribution for which the SRSCB technique has a 95% probability of
      detecting the tumor. In fact, 26.8% had a tumor distribution that was completely
      disjointed from the six recommended biopsy regions. To compare these results with
      other possible occurrence, various biases for the angle of biopsy and the
      distribution of cancer foci were incorporated into the model. Study results
      should be viewed with the understanding that any simulated model has its
      limitations. In our simulated model, the shape of the simulated tumor foci
      (spherical) does not represent all the possible shapes of prostate cancer.
      However, these results indicate that detection of cancer with biopsies taken from
      the apex, middle, and base of each lobe of a prostate with tumor volumes of less
      than 6 cc may not be as effective as it is in prostates with larger tumor volumes
      or patients with an abnormal digital rectal examination. The study of bias models
      suggests that the distributional pattern of cancerous foci can have a significant
      impact on the effectiveness of a given biopsy strategy. CONCLUSIONS: We concluded
      that future attempts to improve systematic biopsy strategies for detection of low
      volume cancer should include biomechanical characteristics of prostate cancer,
      including gland volume and tumor distribution. Driven by the conclusions from
      this idealized model, we have developed a three-dimensional model of the prostate
      gland from its whole-mount histologic maps. It is anticipated that this
      continuing investigation will lead to realistic guidelines for improving biopsy
      techniques.

PMID- 7716841
TI  - Distinguishing prognostic and treatment-predictive information for localized
      prostate cancer.
AB  - OBJECTIVES: To distinguish the concepts of prognostic and treatment-predictive
      information for localized prostate cancer. METHODS: We defined a prognostic
      factor as one that identifies subgroups associated with differing outcomes in
      untreated patients. A treatment-predictive factor identifies patients with
      differing outcomes as a consequence of treatment and is best identified in a
      large, randomized trial. Outside of such a trial, a treatment-predictive factor
      can be identified in prognostic subgroups or after adjustment for prognostic
      factors. RESULTS: The distinctions between prognostic and treatment-predictive
      factors are illustrated by hypothetical examples. CONCLUSIONS: The practical
      implication of the distinctions is that prognostic information may not provide
      reliable treatment-predictive information, that is, additional information may be
      needed before selection of patients for different treatments can be based on
      prognostic information. Determination of the relative treatment effect in any
      prognostic subgroup of patients requires a comparative setting. Until now,
      identified prognostic factors for localized prostate cancer at best can give
      guidance for clinical decisions on which patients should not be offered local
      aggressive therapy if the aim of the therapy is to cure the patient of the
      disease.

PMID- 7716842
TI  - Androgen deprivation with radiation therapy compared with radiation therapy alone
      for locally advanced prostatic carcinoma: a randomized comparative trial of the
      Radiation Therapy Oncology Group.
AB  - OBJECTIVES: Androgen deprivation therapy before and during radiation therapy
      could, by reducing tumor volume, increase local tumor control, disease-free
      survival, and overall survival in patients with locally advanced adenocarcinomas
      of the prostate. METHODS: In a randomized controlled clinical trial, patients
      with large T2, T3, and T4 prostate tumors, but no evidence of osseous metastasis,
      were randomized to receive goserelin 3.6 mg subcutaneously every 4 weeks and
      flutamide 250 mg orally three times daily 2 months before and during the
      radiation therapy course (Arm I) compared with radiation therapy alone (Arm II).
      Pelvic irradiation was administered with 1.8 to 2.0 Gy per day to a total dose of
      45 +/- 1 Gy followed by a boost to the prostate target volume to a total dose of
      65 to 70 Gy. RESULTS: Of 471 randomized patients, 456 were evaluable, 226 on Arm
      I and 230 on Arm II. With a median potential follow-up of 4.5 years, the
      cumulative incidence of local progression at 5 years was 46% in Arm I and 71% in
      Arm II (P < 0.001). The 5-year incidence of distant metastasis on Arms I and II
      was 34% and 41%, respectively (P = 0.09). Progression-free survival rates
      including normal prostate-specific antigen (PSA) levels for 396 patients with at
      least one PSA recorded were 36% in Arm I and 15% in Arm II at 5 years (P <
      0.001). At this time, no significant difference in overall survival could be
      detected (P = 0.7). CONCLUSIONS: Short-term androgen deprivation with radiation
      therapy results in a marked increase in local control and disease-free survival
      compared with pelvic irradiation alone in patients with locally advanced
      carcinoma of the prostate. Long-term surveillance is required to assess effects
      on overall survival.

PMID- 7716843
TI  - Routine prostate biopsies following radiotherapy for prostate cancer: results for
      226 patients.
AB  - OBJECTIVES: To determine the time course of histologic resolution of prostate
      cancer following radiotherapy (RT) and to correlate biopsy results with clinical
      outcome. METHODS: Since July 1990, all patients treated with radical external
      beam RT for prostate cancer at the General Division of the Ottawa Regional Cancer
      Centre have had systematic transrectal ultrasound (TRUS) and TRUS-guided biopsies
      beginning 12 months after RT and then every 6 months until negative or until
      clinical failure. Thus, 226 patients have had 375 TRUS with four to seven
      specimens per examination. Stage distribution was T1b: 32, T1c: 11, T2a: 45, T2b:
      82, T3: 50, and T4: 6. Median follow-up was 33 months. RESULTS: Biopsy results
      were negative in 69.5% of patients by 30 months of follow-up. Thirty-two (14%)
      had local failure (T1b: 12.5%, T1c: 0%, T2a: 11%, T2b: 15%, T3: 18%, T4: 33%).
      Seven (3%) had chemical failure, and 47 (21%) had biopsy-only failure. Median
      follow-up for the biopsy-only failure group is only 19.5 months and mean prostate
      specific antigen (PSA) is 1.0 ng/mL. Thirty-nine patients, initially with biopsy
      only failure, have converted to negative biopsies at a median of 26 months. Nadir
      PSA for patients with local failure was 3.9 ng/mL at 14 months versus 0.7 ng/mL
      at 23 months for those without failure. Patients with late conversion to negative
      biopsy results had a later nadir PSA of 1.3 ng/mL at 27.3 months. CONCLUSIONS:
      Routine prostate biopsy specimens after RT in an unselected population show tumor
      clearance that is in agreement with long-term clinical follow-up, although tumor
      may take more than 30 months to resolve. Nadir PSA can be used to predict
      outcome.

PMID- 7716844
TI  - Estimating the cost effectiveness of total androgen blockade with flutamide in M1
      prostate cancer.
AB  - OBJECTIVES: Although combined androgen blockade with flutamide plus medical or
      surgical castration is effective in metastatic prostate cancer, debate exists
      over whether it is cost effective. METHODS: Decision analysis model of
      hypothetical cohorts of 70-year-old men presenting with metastatic prostate
      cancer, using a societal perspective, calculated anticipated survival and
      incremental cost per life-year gained. Time to progression and survival rate were
      from the Intergroup 0036 trial. Costs were based on Medicare data and wholesale
      drug pricing. Flutamide was estimated to reduce the relative risk of progressive
      disease by 25% (range, 0 to 50%). Costs and survival benefits were discounted at
      a 5% annual rate. RESULTS: In our model for minimal disease, median survival
      increased from 42.3 to 49.4 months with flutamide and average survival by 5.2
      months at an incremental cost of $25,300 per life-year gained. If the efficacy
      were as high as 50%, the benefit would be 12 months at a cost of $13,700 per life
      year gained. At a 10% efficacy, the benefit would be 1.9 months at a cost of
      $60,900 per life-year gained. For severe disease, the model estimated the median
      survival increased from 29.5 to 34.3 months with flutamide and average survival
      by 4.0 months at an incremental cost of $20,000 per life-year gained. At worst
      case 10% efficacy, the benefit decreased to 1.5 months at an incremental cost of
      $47,500 per life-year gained. Total costs for patients treated with an
      orchiectomy and flutamide compared to leuprolide alone were similar if severe
      disease was present and actually lowered costs if there was minimal disease.
      CONCLUSIONS: Flutamide has an incremental cost effectiveness more favorable than
      most accepted therapies. If drug costs are covered under health care reform,
      flutamide should be initiated and covered for all good performance status
      patients.

PMID- 7716845
TI  - Comparison of transvaginal versus laparoscopic bladder neck suspension for stress
      urinary incontinence.
AB  - OBJECTIVES: The purpose of this retrospective review was to determine the
      feasibility of treating anatomic female stress urinary incontinence (SUI) with a
      retropubic laparoscopic bladder neck suspension. Also, we compared the clinical
      course and results of the transvaginal bladder neck suspension (VBNS; Raz) and
      laparoscopic bladder neck suspension (LBNS) among a group of patients of similar
      age and American Society of Anesthesiologists rating. METHODS: Nineteen patients
      undergoing a retropubic LBNS (E.M.M.) were compared with 23 patients undergoing a
      Raz VBNS (C.G.K.) operated on during the same time period for anatomic SUI. All
      patients were assessed for their age, preoperative bladder capacity, preoperative
      postvoid residual, operative time, estimated blood loss, length of hospital stay,
      postoperative analgesia requirement, time required to resume a normal voiding
      pattern, complications, and recurrence rate of the SUI. RESULTS: The operative
      time for the LBNS is longer than the VBNS (124 versus 44 minutes). The LBNS
      patients required significantly less postoperative parenteral analgesia (6.3
      versus 15.6 mg morphine sulfate), and a shorter time to resume a normal voiding
      pattern (0.6 versus 13 days) compared with the VBNS patients. The overall success
      rate of the two procedures was similar at 3 months, 6 months, and 12 months of
      follow-up. CONCLUSIONS: Retropubic LBNS is a technically feasible surgical
      procedure for patients with anatomic SUI. Compared with the VBNS, the LBNS is
      associated with minimal postoperative discomfort, no need for suprapubic urinary
      diversion, and a rapid return to normal activities. The short-term success rate
      of the LBNS appears to be similar to that for the VBNS.

PMID- 7716846
TI  - Comparison of laparoscopic and open retropubic urethropexy for treatment of
      stress urinary incontinence.
AB  - OBJECTIVES: Laparoscopic retropubic urethropexy has recently been described as an
      alternative method to the surgical correction of pure stress urinary
      incontinence. This study compares the operative technique and results of
      laparoscopic colposuspension with traditional open Burch urethropexy to treat
      women with stress urinary incontinence. METHODS: We assessed the short-term
      results of 12 women who underwent a modified laparoscopic Burch urethropexy for
      the correction of stress urinary incontinence and compared these with a similar
      contemporary group of 10 women who underwent a traditional open Burch
      colposuspension procedure. RESULTS: Ten women (83%) who underwent the
      laparoscopic procedure are continent with a mean follow-up of 20.8 months, and 7
      women (70%) who had an open Burch colposuspension are continent at a mean follow
      up of 35.6 months. The laparoscopic procedure took an average of 1.5 hours longer
      than the open repair (P < 0.01). Patients who underwent the laparoscopic
      urethropexy required less postoperative analgesia (mean, 14.2 mg morphine
      equivalents versus 131.4 mg; P < 0.01), shorter length of hospitalization (mean,
      1.9 days versus 4.9 days; P < 0.01), and a more expedient return to normal
      activity when compared with those who underwent open Burch colposuspension.
      CONCLUSIONS: Laparoscopic bladder neck suspension offers a less invasive approach
      to the surgical correction of stress urinary incontinence and can provide
      successful outcomes in properly selected patients.

PMID- 7716847
TI  - Proximal artificial sphincter cuff repositioning for urethral atrophy
      incontinence.
AB  - OBJECTIVES: Recurrent incontinence after implantation of an artificial urinary
      sphincter (AUS) may be due to urethral atrophy. Treatment options consist of
      decreasing the cuff size, increasing the balloon pressure, implanting a double
      cuff system, or proximal cuff repositioning. The first three options may increase
      the risk of erosion. Increasing the balloon pressure does not effectively
      increase cuff pressure. This article demonstrates that proximal cuff
      repositioning is a safe, simple, and effective technique in the management of
      recurrent incontinence as a result of a loss of cuff compression due to urethral
      atrophy. METHODS: Six patients underwent proximal repositioning of the AUS (AS
      800) cuff for recurrent post-prostatectomy incontinence. Urethral atrophy was
      determined by a thorough systematic evaluation. A detailed description of the
      surgical technique is provided. RESULTS: Five of 6 patients (83%) had significant
      improvement in incontinence with an average follow-up of greater than 1 year. In
      1 patient with no improvement, preoperative urodynamics revealed poor detrusor
      compliance in addition to sphincter weakness due to loss of cuff compression.
      CONCLUSIONS: Proximal cuff repositioning on the bulbar urethra is an effective,
      safe, and simple technique in the management of recurrent incontinence due to
      urethral atrophy and may minimize the risk of erosion.

PMID- 7716848
TI  - Evaluation of erectile function in men with sickle cell disease.
AB  - OBJECTIVES: To evaluate and characterize erectile manifestations associated with
      sickle cell disease using nocturnal penile tumescence testing with
      polysomnography (NPT/PSG) and magnetic resonance imaging (MRI) of the penis.
      METHODS: Six variably potent men with sickle cell disease, of whom 5 reported a
      history of priapism, underwent comprehensive evaluations of erectile function.
      Evaluations involved a medical history and physical examination with completion
      of priapism and sexual function questionnaires, followed by NPT/PSG and MRI of
      the penis. RESULTS: Many different erectile abnormalities were identified in this
      group using NPT/PSG, although nocturnal erection durations as well as
      detumescence times were uniformly prolonged. Various axial rigidity measurements
      were obtained, which correlated fairly well with individual reports of erectile
      function. MRI findings ranged from normal corporeal anatomy to corporeal
      destruction with intracorporeal fibrosis and hemosiderin deposition. CONCLUSIONS:
      In sickle cell disease, the erectile dysfunction that commonly occurs may be
      markedly different among men with this disease and may not always be predicted on
      the basis of clinical history of priapism. Generally, clinical assessments of
      erectile function may be derived from clinical histories and physical
      examinations. NPT/PSG and MRI of the penis are in accord with these assessments,
      obviating their routine use, although they may be valuable management adjuncts in
      certain situations.

PMID- 7716849
TI  - Extravesical detrusorrhaphy for refluxing ureters associated with paraureteral
      diverticula.
AB  - OBJECTIVES: To demonstrate the effectiveness of an extravesical approach to
      refluxing ureters associated with paraureteral diverticula. METHODS: Over a 39
      month period, 23 children underwent repair of Hutch diverticula with refluxing
      ureters using an extravesical approach. Seventeen had unilateral reflux with an
      ipsilateral diverticulum, 4 had bilateral reflux with a unilateral diverticulum,
      and 2 had bilateral reflux with bilateral diverticula. Overall, 25 ureters with
      associated diverticula were repaired. RESULTS: Twenty ureters were repaired with
      a nondismembered technique and 5 with a dismembered technique. Twenty-two of the
      23 patients (96%) were successfully repaired with this approach. Three patients
      had transient reflux postoperatively, which resolved spontaneously within 6
      months. One patient who underwent bilateral dismembered procedures for bilateral
      diverticula has persistent unilateral grade II reflux postoperatively. No patient
      developed ureteral obstruction. CONCLUSIONS: The major advantage of this
      technique is seen in the minimal postoperative morbidity. The extravesical
      approach is a safe, simple, and effective method for the management of a
      refluxing ureter with an associated diverticulum.

PMID- 7716850
TI  - Color Doppler ultrasound in newborn testis torsion.
AB  - OBJECTIVES: To assess the usefulness of color Doppler ultrasound in evaluating
      the newborn with suspected antenatal testis torsion. METHODS: Nine newborns with
      10 antenatally torsed testes were examined using color Doppler and gray-scale
      ultrasound. RESULTS: Each examination revealed lack of intratesticular blood flow
      on the affected side and normal flow within the contralateral testis. In
      addition, gray-scale sonographic architecture of the affected testes appeared to
      reflect the duration of in utero torsion. CONCLUSIONS: Color Doppler sonography
      accurately assesses intratesticular blood flow in newborns with antenatal testis
      torsion and offers interesting details.

PMID- 7716851
TI  - Application of the flexible cystoscope to the excision of renal cell carcinoma
      with intracaval tumor thrombus.
AB  - Cardiopulmonary bypass, temporary cardiac arrest, and exsanguination have
      facilitated the surgical resection of renal tumors with intracaval thrombi that
      extend above the hepatic veins or into the atrium. The bloodless field provided
      by this approach enables the surgeon to utilize a flexible cystoscope to ensure
      that the caval thrombus has been removed entirely from the hepatic veins.

PMID- 7716852
TI  - Suture guide for retropubic vesicourethral suspension.
AB  - Retropubic suspension of the urethrovesical neck can be facilitated with the use
      of a metal suture guide. This guide permits efficient, accurate placement of
      paravaginal sutures and eliminates the risk of finger needle puncture, thus
      reducing operative time and providing a safer technique.

PMID- 7716853
TI  - Mullerian duct cyst masquerading as chronic prostatitis: diagnosis with magnetic
      resonance imaging using a phased array surface coil.
AB  - Prostatitis is a common clinical syndrome that on rare occasions may result from
      mass lesions in the pelvis. This report concerns a man with debilitating
      prostatitis that was caused by a mullerian duct cyst. The diagnosis was
      facilitated by examination with magnetic resonance imaging using a pelvic phased
      array surface coil and a small field of view.

PMID- 7716854
TI  - Laparoscopic orchidopexy in the prune belly syndrome: a case report and review of
      the literature.
AB  - The management of the testicles in the prune belly syndrome can be problematic
      after the neonatal period. Laparoscopic orchidopexy has been used for the intra
      abdominal testis with success. A case of bilateral laparoscopic orchidopexy in a
      child with prune belly syndrome is presented. The testes were brought to the
      scrotum without division of the spermatic vessels, taking advantage of the
      extensive intra-abdominal dissection possible laparoscopically. This case
      demonstrates that therapeutic laparoscopic procedures are possible in the prune
      belly syndrome and that laparoscopic orchidopexy may have promise in older
      affected children or in those requiring no other concomitant surgery.

PMID- 7716855
TI  - Penile intracavernosal substance abuse.
AB  - A complete workup for a 36-year-old man with unexplained inguinal adenopathy and
      an indurated, enlarged penis and scrotum included urine cultures for bacteria,
      fungi, and acid-fast bacilli; scrotal ultrasound; computed tomography of the
      abdomen and groin; a retrograde urethrogram; a cystogram; duplex penile Doppler
      blood flow studies; and a surgical inguinal lymph node dissection. Pathologic
      examination of the excised lymph node revealed lipoid granulomatous
      lymphadenitis. After receiving definitive treatment for a psychotic condition,
      the patient acknowledged a 2-year history of intracavernosal injection of
      gelatinous vitamin E.

PMID- 7716856
TI  - Palisaded encapsulated neuroma of the glans penis.
AB  - A case is reported of an 84-year-old white man in whom a palisaded encapsulated
      neuroma (PEN) had developed in his glans penis over the course of 50 years. It
      represents a distinctive cutaneous nerve sheath tumor that consists of an
      overgrowth of both axons and Schwann cells and is surrounded by a complete or
      incomplete capsule of perineural cells. This entity warrants wider recognition by
      urologists and uropathologists. To our knowledge this is the first description of
      this kind of tumor in the glans penis.

PMID- 7716857
TI  - A comparative assessment of cryosurgical devices: application to prostatic
      disease.
AB  - OBJECTIVES: To determine the comparative freezing ability of the Cryotech (CT)
      and AccuProbe (CMS) cryosurgical systems. METHODS: Four conditions designed to
      model clinical situations were produced: (1) Single-probe performance in water at
      17 degrees C; (2) five-probe performance in water at 17 degrees C; (3) single
      probe performance in gel at 22 degrees C; and (4) single-probe performance in
      bovine liver. Parameters evaluated included temperatures at various time points
      (rates to and final low temperature), configuration of a freeze zone, and shaft
      freezing characteristics. In addition, isotherms were measured at predetermined
      distances from the center of the freeze zone. RESULTS: Both systems provided
      freezing of various media under operational conditions. In water, the CMS 3-mm
      probe delivered more rapid freezing temperature rates than the 3-mm CT probe,
      with a 110 degrees C difference in probe surface temperature. In gel, the CMS
      probe increased freeze volume fourfold versus a twofold increase for the CT
      probe. In bovine liver, there was nearly equivalent performance with respect to
      geometry of the freeze ball. Extrapolation of the CT cooling curve indicated
      temperature equivalence at 30 minutes. A larger shaft diameter 4.9-mm CT probe
      produced results similar to the CMS probe in all the tested media. In addition,
      the freeze configuration of the CMS probe was spherical; the CT configuration was
      more cylindrical. CMS probe (equivalent diameter) tip temperatures were on
      average 100 degrees C lower. CONCLUSIONS: Our tests demonstrated differences
      between the CMS and CT probe. The major differences are in the configuration of
      the freeze zone and shaft freezing. In equivalent conditions, the CMS 3-mm probe
      delivered more rapid cooling rates, a more spherical freeze ball, and lower
      absolute temperatures than the CT 3-mm probe. The larger CT probe produces
      equivalent freezing temperatures to the CMS probe, albeit with a more spherical
      shape. However, these in vitro systems may not adequately reflect varied prostate
      morphology. Further research is under way to determine if these differences
      affect relative efficacy of cryotherapy of the prostate.

PMID- 7716858
TI  - Cytolethality of hemolytic Escherichia coli to primary human renal proximal
      tubular cell cultures obtained from different donors.
AB  - OBJECTIVES: In earlier experiments, we confirmed epidemiologic studies
      demonstrating the prominence in acute pyelonephritis of Escherichia coli
      expressing P fimbriae and hemolysin, produced the disease with pyelonephritogenic
      strains in an animal model, and developed in vitro assays using human renal
      proximal tubular cells that demonstrated bacterial adherence by P fimbriae and
      killing of the renal cells by hemolysin. In the present series of experiments, we
      sought to determine whether P-fimbriated hemolytic E coli killed human renal
      proximal tubular epithelial cells obtained from different human donors. METHODS:
      Human renal proximal tubular cells, putative target cells for bacteria causing
      acute pyelonephritis, were cultured from 9 donors and cell death was measured by
      two methods. RESULTS: We showed that the E coli strain was significantly more
      cytolethal for renal cells of all donors than its hemolysin-negative mutant.
      CONCLUSIONS: This work suggests that the pathogenesis of acute pyelonephritis by
      P-fimbriated hemolytic E coli, characteristics of the causative organism in about
      50% of human cases, may be at least in part through killing of human renal
      epithelial cells by hemolysin.

PMID- 7716859
TI  - Effects of naloxone on regional norepinephrine content of the rabbit urinary
      bladder after electrical pelvic floor stimulation.
AB  - OBJECTIVES: Effect of opioid blockade on regional norepinephrine content of the
      rabbit urinary bladder was investigated under electrical pelvic floor
      stimulation. METHODS: Norepinephrine content of the bladder body and base of the
      rabbit was estimated by high-performance liquid chromatography in the following
      four subgroups: control group; group 1, treated by electrical stimulation; group
      2, treated by naloxone alone; and group 3, treated by electrical stimulation and
      naloxone. RESULTS: Intravenous administration of naloxone (group 2) caused
      depletion of norepinephrine content in the bladder body (P < 0.001).
      Norepinephrine content in the bladder base was also reduced, although this
      difference was not statistically significant. Electrical stimulation to the
      pelvic floor musculature (group 1) increased norepinephrine content both in the
      bladder base and the body (P < 0.01). Such a norepinephrine elevation disappeared
      in the rabbit treated by electrical stimulation plus naloxone (group 3).
      Norepinephrine content of this group was almost the same as those treated by
      naloxone alone. CONCLUSIONS: Opioid blockade appeared to block the hypogastric
      nerve activation induced by electrical pelvic floor stimulation.

PMID- 7716860
TI  - Apomorphine versus mating behavior in testing erectile capabilities of diabetic
      rats.
AB  - OBJECTIVES: Diabetes mellitus (DM) is an important cause of organic impotence. It
      is estimated that 35% to 75% of diabetic patients are impotent. In the present
      study we investigated the effect of experimentally induced diabetes (streptozocin
      60 mg/kg, intraperitoneally, for 9 weeks) on sexual behavior and compared it to
      the apomorphine (APO) bioassay test. METHODS: Libido, genital reflex
      excitability, and penile competence as measured by different parameters of mating
      behavior were reduced with DM (P < 0.05 versus control for each parameter).
      RESULTS: Of 17 diabetic rats, 53% (9 rats) experienced positive mating behavior
      (either intromission or ejaculation) compared with 82.4% (14 rats) positive
      response to the APO bioassay test. Moreover, combined apomorphine injection and
      mating sexual testing in diabetic rats that achieved intromission but not
      ejaculation or those that did not achieve intromission in the initial mating,
      considerably improved the performance of these rats. CONCLUSIONS: We suggest that
      the APO test alone or, even better, combined APO injection and sexual testing are
      superior in eliciting maximum erectile capabilities of the diabetic rats than
      mating testing alone.

PMID- 7716861
TI  - Synergy between protamine and vancomycin in the treatment of Staphylococcus
      epidermidis biofilms.
AB  - OBJECTIVES: To test for synergy between protamine and vancomycin by analyzing
      their bactericidal activities against slime-producing Staphylococcus epidermidis
      ATCC 35983 under planktonic and biofilm conditions. METHODS: We evaluated the
      activity of vancomycin and protamine separately against planktonic S epidermidis
      in broth by measuring the minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC) for each agent according to the standard
      macrobroth dilution method. To assess the possibility of synergy between these
      two agents, planktonic S epidermidis was exposed to vancomycin and protamine
      together in varying concentrations. Biofilms containing S epidermidis were then
      prepared and subjected to incubation with vancomycin and protamine separately as
      well as combined in varying concentrations. The bacterial viability of S
      epidermidis in the planktonic and biofilm phases after exposure to these two
      agents was assessed by qualitative culture and determination of viable colony
      blots. RESULTS: Standard antibacterial susceptibility tests revealed that the
      MICs of protamine and vancomycin were 1 and 2 micrograms/mL, respectively, and
      their MBCs were 4 micrograms/mL. The MICs were unchanged when protamine and
      vancomycin were combined in varying concentrations. Neither agent exhibited
      significant bactericidal activity against S epidermidis in the biofilm phase at
      concentrations < or = 32 micrograms/mL. However, a combination of both agents,
      each at 32 micrograms/mL, resulted in a 7-log decrease in viable bacterial
      counts. CONCLUSIONS: Protamine alone exhibited significant antibacterial activity
      against planktonic S epidermidis. No synergy was noted between protamine and
      vancomycin against S epidermidis in the planktonic phase. However, synergy was
      demonstrated when a combination of protamine and vancomycin was used on S
      epidermidis in the biofilm phase. Thus, protamine shows promise as an adjunctive
      agent to vancomycin in the treatment of S epidermidis in biofilms.

PMID- 7716862
TI  - Comparative between-laboratory trials of the liquid-phase blocking sandwich ELISA
      for the detection of antibodies to foot-and-mouth disease virus.
AB  - Fifty bovine serum samples were tested for the presence or amounts of antibodies
      to foot-and-mouth disease (FMD) virus serotypes A, O and C by the liquid-phase
      blocking sandwich ELISA (lpb-ELISA) using reagents prepared by the World
      Reference Laboratory for Foot-and-Mouth Disease (WRL) in Pirbright, U.K. Twenty
      of the sera had been collected before extensive vaccination with a commercial
      inactivated trivalent FMD vaccine was ceased and the remaining thirty originated
      from animals which had not been vaccinated for more than one year. After the test
      had been completed, the samples were sent to another two laboratories to be
      examined by the same assay. Results obtained in the laboratories were compared to
      assess the degree of agreement in serological tests for FMD in cattle. Antibodies
      to at least one of the three FMD virus (FMDV) serotypes were demonstrated in 70%
      of the serum samples. Antibodies to the antigens A5, O1 and C1 were present in
      58%, 66% and 58% of the sera, respectively. The overall between-laboratory
      agreement of the results of the lpb-ELISA for the detection of antibodies against
      all three serotypes was 96%. Discrepancies in terms of type specificity did not
      exceed 10%. Most discrepancies were recorded in sera with low antibody titres or
      optical densities (OD) around the cut-off point. An increase of concentration of
      C1 antigen in reaction mixture reduced the sensitivity of ELISA and results of
      screening tests became negative in sera with antibody titres of 1: 90 and
      lower.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716863
TI  - [The effect of primarily mercury heavy metal emissions on pasture helminthiasis
      in sheep].
AB  - A group of 30 improved Valashka sheep, grazed in submontane pastures 3 and 6 km
      far from the emission source of mercury-dominated heavy metals (L1 and L2) and in
      pasture situated out of mercury emission fall-out (K), were investigated for the
      prevalence and mean intensity of pasture helminth infection. Hg concentration in
      the grass stand was determined by the distance of emission source. The amount of
      mercury was increasing in the direction from control locality to locality 1,
      lying 3 km from the emission source. With the mean concentration of 4.298 mg
      Hg/kg in grass stand, 0.346 mg Hg/kg in the liver, 0.591 mg Hg/kg in the kidneys
      and 0.030 mg Hg/kg in the muscles (Tab. I) a high prevalence of pasture helminths
      was recorded in sheep. This prevalence was increasing in the direction from
      control locality to the nearest emission source (Tab. II). The only exception was
      Moniezia spp. and Strongyloides papillosus, with values at locality 2 being lower
      than those at control locality. Trichostrongylus spp. and Cooperia spp. were
      equally prevalent at all the localities studied. Mean infection intensity (Tab.
      III) showed an increasing tendency from control locality towards locality 1. Only
      Dicrocoelium dentriticum and Strongyloides papillosus were an exception, with the
      highest mean infection intensity recorded at locality 2 (5.3 and 3.3 specimens,
      respectively). The highest mean intensity at control locality was recorded for
      Cooperia spp. infection (4.5 specimens). Mean infection intensity at locality 2
      (6 km from emission source) and control locality showed proximate values in
      Moniezia spp. (1.3-1.2 specimens), Nematodirus spp. (2.6-2.4 specimens) and
      Cooperia spp. (4.0-4.5 specimens).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716864
TI  - [Effectiveness of azamethiphos-based insecticides against the housefly (Musca
      domestica L.)].
AB  - The insecticidal baits Muscalik-AZA (dust formulation) and Snip (granulated
      formulation) contained the active ingredient azamethiphos--1% and special fly
      attractant Z-9-tricosen--0.2%. Toxicity of these baits was monitored in 4 wild
      resistant strains of M. domestica (Diptera: Muscidae) which were marked according
      to the locality of collection as J, KP, NC and NL and in 1 sensitive strain
      WHO/SRS. KT90 in resistant strains was in the range from 1.5 to 6.5 hrs at
      testing of Muscalik-AZA. The efficiency of Muscalik-AZA was manifested with 100%
      knock-down effect in all tested strains with exception of KP strain after 24 hrs.
      During the experiments with Snip the greater range of knock-down time for 90% of
      tested strain was observed. KT90 was in the range from 5 hrs to > 24 hrs. After
      24 hrs a range between 83-97% of knock-down effect was found in all tested
      strains. In field conditions of the weaned piglets rearing, the efficiency of
      Muscalik-AZA in flies highly resistant to azamethiphos was in the range from 14
      to 21.9% during 28 days. Efficiency of Muscalik-AZA in the the range between 80
      91.7% was determined in the delivery room for sows in flies with low resistance
      to azamethiphos. The biological efficiency of Snip to flies with moderate
      resistance to azamethiphos was determined in the area of veterinary ambulance.
      The mean efficiency of Snip was 92.2% during the 28 days of test.

PMID- 7716865
TI  - [Survival of Ascaris suum eggs in sewage treatment plant sludge].
AB  - In the period between June 1992 and May 1993 the survival of nonembryonated eggs
      of A. suum was studied in two sludge drying beds of sewage treatment plants (STP)
      under different climatic-geografical conditions: STP Michalovce in the East
      Slovak Lowland (elevation 111 m above sea-level) and STP Poprad in the submontane
      area of the Poprad valley (elevation 695 m). Sludge drying beds of both sewage
      treatment plants (STP) showed different survival of eggs (Fig. 1). In STP
      Michalovce we detected a rapid reduction in viable eggs from October through
      December (from 80.4% at the initiation of the experiment to 19.8% in December
      1992). Later this decrease became less rapid and at the end of the experiment,
      after 240 days only 5% of eggs were viable. In STP Poprad the viability of eggs
      was reduced rather gradually, and after 320 days of exposure 36% of viable A.
      suum eggs were still recorded. Sludge dry matter in STP Poprad increased from
      2.2% to 14.2% and in STP Michalovce from 4.1% to 19.2% at the termination of the
      experiment. Sludge pH showed no marked variation in both STPs, ranging between
      7.1 and 7.8. The percentage of sludge organic matter was higher in STP Poprad,
      ranging from 55 to 75%, than in STP Michalovce, with 34-31%. We studied the
      correlation coefficients (Tab. I) of exposure time, air temperature, sludge
      drying bed temperature at 10 cm depth, pH, dry matter (Figs. 2 and 3) to the
      viability of model A. suum eggs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716866
TI  - [Characteristics of the plasmid profile of inositol- and rhamnose- negative
      strains of Salmonella typhimurium].
AB  - S. typhimurium isolates obtained during a large outbreak of human salmonellosis
      associated with smoked mackerels in the Czech Republic as well as strains of S.
      typhimurium isolated from black headed gull (Larus ridibundus) were examined
      following biotyping, phage typing, plasmid profiling and restriction endonuclease
      analysis (Eco RI, Hind III and Bam HI) of plasmid DNA. The epidemic strain of S.
      typhimurium and two isolates from environment of nesting colony black-headed gull
      were meso-inositol and L-rhamnose negative, phage type 141. The isolates from
      human and environment of nesting colony were found to share the same plasmid
      profile and REA.

PMID- 7716867
TI  - [Association between BoLA antigens and bovine mastitis].
AB  - The association between BoLA class I antigens and mastitis was studied in
      Bohemian Pied breed (n = 17) and its crosses--Bohemian Pied x Red Pied Holstein
      (n = 161), Bohemian Pied x Red Pied Holstein x Ayrshire (37). The diagnostics of
      mastitis was followed in the course of two years and two diagnostic parameters
      were included: 1. a modified California Mastitis Test (CMT) was performed once a
      month; 2. a bacteriological infection was examined once quarterly using
      biochemical and serological methods. BoLA class I antigens were determined by
      specific antisera in the standard microlymphocytotoxicity test. During testing
      the majority of cows had at least one positive reaction of CMT test. The
      bacterial findings were detected in 31.63% of animals. The antigen A16 was found
      to be significantly associated with susceptibility to mastitis in both diagnostic
      tests. Animals A16 positive showed the highest CMT values and repeated bacterial
      infections (Fig. 1). The high values observed in A2 positive animals were not
      significant due to the very low frequency of this allele in the population under
      study. There was a slight increase of CMT values and the infection frequency in
      animals with higher parity number (Fig. 2). However, the order of lactations did
      not influence the relationship of BoLA A16 and mastitis. This association was not
      significantly affected by the breed. The increased bacterial infection observed
      in the Bohemian Pied breed is likely due to relatively high incidence of A16
      allele rather than to breed differences (Fig. 3).

PMID- 7716868
TI  - Veterinary education in Britain and the US.

PMID- 7716869
TI  - Primary cutaneous listeriosis in adults: an occupational disease of veterinarians
      and farmers.
AB  - Seventeen cases of cutaneous listeriosis in adults are reviewed. The condition
      appeared as papular or pustular lesions on the arms or hands, and was most often
      acquired as an occupational hazard from infected animals. The cases were all mild
      and were resolved successfully. However, listeric infections are potentially
      fatal, and as the initial cause of the lesion may be unknown, it is recommended
      that veterinarians and farmers should have suspect lesions examined
      microbiologically.

PMID- 7716870
TI  - Factors affecting the rate of growth of ostrich (Struthio camelus) chicks in
      captivity.
AB  - A set of 120 ostrich eggs was imported into the United Kingdom under class 1
      quarantine restrictions. The chicks hatched were initially reared in mixed size
      groups and weighed daily to monitor their health. Ten days after hatching the
      chicks were separated into four groups, based on their weight, which were kept
      under identical conditions, fed ad libitum and weighed daily. At the end of the
      35 day quarantine period the growth rates of the chicks were correlated with
      their weight on day 10: the heaviest chicks remained the heaviest. In addition,
      the degree to which the chicks lost weight and the period for which they did so
      was also related to their weight on day 10. However, the smallest chicks on day
      10 grew more quickly than the largest chicks. Chicks which had been helped to pip
      and hatch showed poor survival rates and low rates of growth. The growth rate of
      the ostriches appeared to be influenced by environmental factors.

PMID- 7716871
TI  - Post mortem condemnation returns from poultry slaughterhouses in England and
      Wales.

PMID- 7716872
TI  - Exercise induced pulmonary haemorrhage in racing camels.

PMID- 7716873
TI  - Skin lesions associated with herpesvirus-like particles in frogs (Rana
      dalmatina).

PMID- 7716874
TI  - Intestinal diverticulitis in a nilgai (Bucelaphus tragocamelus).

PMID- 7716875
TI  - Use of medicines: a dangerous cascade.

PMID- 7716876
TI  - Future of the State Veterinary Service.

PMID- 7716877
TI  - Prevention of rabies.

PMID- 7716878
TI  - Statutory examination for membership.

PMID- 7716879
TI  - Development and evaluation of an indirect ELISA to detect antibodies to abortion
      strains of Chlamydia psittaci in sheep sera.
AB  - A novel indirect enzyme-linked immunosorbent assay (ELISA) for antibodies against
      abortion strains of Chlamydia psittaci (C. psittaci) has been developed. The
      antigen used was chlamydial elementary bodies treated sequentially with N-lauroyl
      sarcosine and n-octyl-beta-D-glucopyranoside and finally solubilized with N
      lauroyl sarcosine and dithiothreitol. Treating the antigen with sodium periodate
      after coating of the plates increased the specificity for antibodies to abortion
      strains. The test was evaluated initially with sera from experimentally infected
      sheep and an uninfected control group. These sheep were monitored for lambing
      performance and infection status. When used in conjunction with the indirect
      micro-immunofluorescence test (MIF), the ELISA was able to identify as negative
      all twenty-five sera from ewes that had no typical placental lesions and
      identified as positive twenty of twenty-one sera from infected ewes that had
      either typical placental lesions or had been found positive by isolation of
      chlamydia in cell culture. The combination of ELISA and MIF was also able to
      discriminate correctly groups of sera from six flocks with a history of infection
      from four known uninfected flocks.

PMID- 7716880
TI  - Identification of Escherichia coli strains from cows with clinical mastitis by
      serotyping and DNA polymorphism patterns with REP and ERIC primers.
AB  - A number of Escherichia coli strains was isolated during a study of clinical
      mastitis on seven farms in the Netherlands. From these E. coli strains, 30 were
      characterised with regard to their serotype and their DNA polymorphism pattern
      with REP and ERIC primers. Special attention was given to recurrent E. coli
      mastitis in cows. The combination of serotype and DNA pattern observed, was used
      to study the epidemiology of clinical E. coli mastitis. The results demonstrated
      that the PCR reaction with the ERIC primers can be used for differentiation of E.
      coli strains. The DNA polymorphism patterns showed that E. coli strains isolated
      from cases of clinical mastitis have a great variability in genotype. More 3 than
      one case of clinical mastitis associated with E. coli during the same lactation
      period occurred infrequently. However when it took place, E. coli strains
      isolated from the separate episodes of inflammation, were in most instances of
      the same serotype and had the same DNA amplification pattern.

PMID- 7716881
TI  - Antibody response against Pseudomonas aeruginosa membrane proteins in
      experimentally infected sheep.
AB  - Shedded sheep inoculated epicutaneously with P. aeruginosa and then wetted
      experimentally by a sprinkler system, rapidly develop a green bacterial stain.
      This was associated with an outpouring of serious exudates onto the skin surface
      in the fleecerot lesion site. Histopathological analysis of dermatitic lesions
      revealed an infiltration of polymorphonuclear leucocytes into the dermis and the
      formation of a mosaic of microabscesses beneath the sloughed sheets of cornified
      epithelium. P. aeruginosa if present, was always localized as aggregates at the
      leading front of the seropurulent exudate and was never observed to invade the
      dermis. Animals that had been inoculated with P. aeruginosa but kept dry, showed
      no signs of dermatitis or serological reactivity against the inoculated
      bacterium. In contrast, sheep that had been inoculated and wetted, reacted
      serologically against P. aeruginosa whole cells in an enzyme-linked immunosorbent
      assay (ELISA). Eleven of 18 sheep were considered to be high-antibody responders
      and registered an ELISA ratio > 2.5 at one or more time points over the duration
      of the experiment (14 weeks). Analysis of ELISA reactivity of fleecerot sheep
      against fractionated cell envelope proteins of P. aeruginosa showed a
      preferential antibody response to outer (OMP) rather than inner (IMP) membrane
      proteins. Immunoblots revealed strong antibody activity against 2 major OMPs-Opr
      F and Opr H with apparent molecular masses of 39 and 21 kDa respectively. OMPs
      prepared from sarkosyl-resistant outer membrane vesicles were electrophoretically
      identical to OMPs prepared by a more rapid and efficient organic phase
      partitioning procedure (Chin and Dai, 1990). Although two other OMPs-Opr E (44
      kDa) and Opr G (25 kDa) were seen in Coomassie blue-stained SDS-PAGE gels of P.
      aeruginosa OMPs, they were not reactive with sera from fleecerot affected sheep.
      It is likely that sheep with high levels of circulating serum antibody against
      major outer membrane proteins of P. aeruginosa may, in the event of a fleecerot
      episode, exude such antibodies onto the skin surface. This could provide a
      strategy for the control of ovine fleecerot by vaccination if highly conserved
      outer membrane proteins of P. aeruginosa were found to be protective.

PMID- 7716882
TI  - Experimental streptococcal meningo-encephalitis in cultured fish.
AB  - In 1984 a disease of fish appeared in Israel which spread rapidly in cultured
      fishponds. The disease affected tilapia (Oreochromis aura x Oreochromis nilotica
      hybrids) and trout (Oncorhynchus mykiss). Common carp (Cyprinus carpus), although
      reared in community with tilapia were not susceptible to the disease. Various
      species of ornamental cyprinids and cichlids were also affected. Morbidity was
      high and mortality ranged between 50% (in trout) and 30% (in tilapia). Clinical
      and pathological findings indicated that the tilapia and trout suffered from
      meningitis and menigo-encephalitis. Two new streptococcal species, Streptococcus
      shiloi and Streptococcus difficile were isolated from diseased fish. The disease
      was reproduced experimentally in both trout and tilapia with the two
      streptococcal species. The LD50s of S. shiloi and S. difficile strains cultured
      in vitro (two to three passages on BHI medium) were 10(7)-10(8) cfu. The
      virulence of these strains was increased (LD50:10(2)-10(5) cfu) after three
      passages in vivo (brain to brain passage in fish without culture on agar plates).
      Highly virulent strains did not differ from low virulent strains by any
      identifiable extrachromosomal elements.

PMID- 7716883
TI  - Construction of recombinant Shiga-like toxin-IIv (SLT-IIv) and its use in
      monitoring the SLT-IIv antibody status of pigs.
AB  - We constructed and purified recombinant B-subunits of the SLT-IIv as well as
      tested their usefulness in an immunoblot assay. The slt-IIvB gene amplified by
      PCR was ligated into the fusion vector pGEX-2T, and expressed in E. coli K 12
      laboratory strains. Deletion of the signal sequence was necessary for optimal
      expression. High quantities of the fusion protein could be purified by affinity
      chromatography and subsequently used as antigen for immunoblot analysis with
      serum samples from diseased pigs and healthy controls. IgG antibodies against SLT
      IIv were detected in the sera of 11 of 52 (21.15%) healthy pigs. By contrast,
      only in 1 of 28 (3.57%) serum samples of pigs with edema disease caused by SLT
      IIv-producing E. coli we could demonstrate SLT-IIv-specific antibodies. During an
      outbreak of edema disease, sera from 10 pigs were taken at 4, 20, and 40 days
      after disease onset to investigate the immune response elicited by SLT-IIv.
      Immunoblot analysis with the recombinant SLT-IIv fusion protein revealed that the
      number of IgG-positive serum samples increased within this period of 40 days from
      one on day 4, to seven on day 20, to ten on day 40; the number of IgM-positive
      samples also increased from one after 4 days to eight after 20 days. Forty days
      after disease onset, IgM reactivity was no longer detectable. Since all animals
      seroconverted in the follow-up sera, the antigenicity of SLT-IIv during infection
      of pigs seems to differ from that of SLT-II in human hemolytic uremic syndrome
      where only a minority of patients are known to mount an immune response. The
      recombinant SLT-IIvB described here may be a possible candidate for vaccination
      trials.

PMID- 7716884
TI  - Influence of passive immunity on pig immunization with deleted Aujeszky's disease
      vaccines measured by the amount of wild virus excretion after challenge.
AB  - Four attenuated glycoprotein I deleted Aujeszky's disease virus (ADV) vaccines
      were compared on the basis of their ability to induce immunity in the presence of
      passive antibodies. The relative severity of clinical disease and amount of viral
      excretion following experimental challenge with virulent ADV were determined
      among groups of eight pigs that were unvaccinated or vaccinated with one of the
      four ADV vaccines. Vaccinated pigs received two vaccine doses, the first
      administered when passively acquired serum antibodies were still detectable at 10
      weeks of age, and the second four weeks later. The experiment was divided into
      two trials, with vaccinated and unvaccinated control groups in each trial.
      Challenge with virulent ADV took place at 18 weeks of age for the first lot and
      19 weeks of age for the second. Differences among the vaccines were observed with
      regard to clinical protection and viral excretion. Virulent virus was excreted by
      most of the vaccinated pigs from two to seven days after challenge. In the case
      of two of the vaccines, no virus excretion was detected in several of the pigs.
      It was confirmed that mean serum neutralizing titers at challenge are inversely
      associated with amount of viral excretion post-challenge. Difficulties in the
      standardization of vaccine trials with passive antibodies were discussed.

PMID- 7716885
TI  - A double monoclonal antibody ELISA for detecting pestivirus antigen in the blood
      of viraemic cattle and sheep.
AB  - A panel of monoclonal antibodies (mAbs) has been produced to the p125/p80 non
      structural polypeptide of border disease virus (BDV) and bovine virus diarrhoea
      virus (BVDV). This polypeptide appears to be highly conserved among BDV and BVDV
      isolates and consequently the mAbs directed against it have a broad cross
      reactivity with pestivirus isolates. The epitope specificities of these mAbs were
      determined by competitive binding and four of the mAbs with mutually exclusive
      epitope specificities were selected for the development of a diagnostic ELISA.
      Two mAbs were used to capture virus antigen prepared from the blood of infected
      cattle and sheep, then two different mAbs used to detect the captured antigen.
      This double mAb ELISA was compared to existing ELISAs which rely on polyclonal
      antibodies (pAbs) for detecting captured antigen. The mAb detection ELISA was
      more sensitive than the pAb detection ELISAs for both cattle and sheep and
      resulted in higher optical densities for positive samples without an increase in
      background readings of negative controls.

PMID- 7716886
TI  - A competition ELISA for the detection of antibodies to rabbit haemorrhagic
      disease virus.
AB  - Monoclonal antibodies (mAbs) were raised to a preparation of rabbit haemorrhagic
      disease virus (RHDV) purified from the livers of experimentally infected rabbits.
      Rabbit antisera to RHDV significantly blocked the binding of two mAbs (2D3(3) and
      2D4(5)) to RHDV-coated microplate wells in a competition ELISA. The virus
      specific nature of these mAbs was confirmed by immunoperoxidase and
      immunofluorescence assays on formalin-fixed and fresh infected liver tissue.
      Utilization of one of these mAbs (2D3(3)) in a competition ELISA, resulted in an
      RHDV antibody assay which proved more specific than an indirect ELISA and more
      rapid and reliable than a haemagglutination inhibition assay for screening serum
      samples from wild and experimental rabbits.

PMID- 7716887
TI  - [Structural variants in hemoglobin occurring in the Czech Republic].
AB  - The authors present a review of clinical and laboratory findings of seven in the
      Czech Republic hitherto diagnosed structural haemoglobin variants. Unstable
      variants are found most frequently: Hb-Koln, Hb-St. Louis, Hb-Nottingham, Hb-E
      and Hb-Hradec Kralove. The variant Hb-Hradec Kralove (Hb-HK) or alpha 2 beta 2
      115 (G17) Ala-Asp was newly detected. The great instability of Hb-HK chains makes
      classical diagnosis of Hb-pathy impossible. It was possible to identify it only
      at a molecular genetic level. A manifestation of Hb-HK instability is also the
      thalassaemic feature of the disease and the formation of Heinz bodies from free
      chains. The only representative of haemoglobins with a high oxygen affinity
      identified in this country was newly detected. It was given the name Hb-Olomouc
      or alpha 2 beta 2 86 (F2) Ala-Asp. This haemoglobin variant leads to
      erythrocytosis in father and son and the same clinical manifestations were
      recently described also in Japan. The last structural variant of haemoglobin
      found in this country is Hb-M Milwaukee or alpha 2 beta 2 67 (E11) Val-Glu which
      in our patients is manifested rather by haemolysis with formation of Heinz bodies
      than classical cyanosis. The cause of instability of Hb-M in our patients is not
      known. Hb-S was not diagnosed so far in the Czech Republic.

PMID- 7716888
TI  - [Subcutaneous chamber systems (ports) for long-term care in cancer patients].
AB  - Maintenance of satisfactory and safe venous access in cancer patients is part of
      a comprehensive care of cancer patients. As the Hickman/Broviac catheter is today
      used an implantable port. This port is placed in a subcutaneous pocket. The
      catheter connected to the port leads into the central vein, usually through the
      subclavian vein. An application of drugs in the port is done trough the skin. In
      this time could be used different types of ports, one or two chambers port, low
      profil port, peripheral port and others. In this paper we reported our two-years
      experience with 33 totally implantable access systems, which has been implanted
      in patients with cancer in Masaryk University Hospital Brno Bohunice. In our
      department was most frequently used port the nonmetallic port IMPLANTOFIX (BRAUN
      MELSUNGEN). All ports were in place for a total of 5,582 days, in average of 169
      days. A frequency of complications were 2.15 on 1,000 days. Four ports were in
      place for longer than 1 year. A comparison of the incidence of complications in
      the present study with an analysis of 23 studies reported in literature was
      satisfactory. Minimal maintenance care, no restriction of life activity,
      improving quality of life and probably less frequency of infection complications,
      identify it as a significant advantage for the satisfactory maintenance of venous
      access of oncology patients in comparison with Hickman/Broviac catheter. Both the
      patients and the nursing staff showed a very high degree of satisfaction with
      this system. In cancer patients, especially with poor venous access, and
      prognosis longer than 6 months can be indicated this system with the advantage
      for patients.

PMID- 7716889
TI  - [Immunocytochemical phenotyping of centroblastic lymphoma cells].
AB  - Using immunocytochemical phenotyping, the authors assessed the origin of
      malignant cells in a patient with malignant centroblastic lymphoma. The lymphoma
      cells expressed the thymocytic surface molecule CD1, pan T-lymphocytic markers
      CD2, CD5, CD6, CD7 with concurrent absence of complex CD3 and receptors for
      antigen on T lymphocytes. The proliferating activity of malignant cells could not
      be controlled by intensive cytostatic therapy.

PMID- 7716890
TI  - [Hemocoagulation and hemorheology in heart failure and the possible effects of
      glycosaminoglycans].
AB  - Chronic congestive heart failure is one of the risk groups of acquired
      hypercoagulant and hyperviscous state. In a group of patients with medium and
      severe cardiac failure the administration of sulodexide led to an increased
      activation of the fibrinolytic potential--a drop of PAI-1 and fibrinogen, to an
      increased activation of anticoagulatory potential--an increase of AT III and
      reduced plasma viscosity. Global coagulation and biochemical screening parameters
      were not affected by treatment. Administration of the preparation did not exert
      important undesirable effects and was well tolerated.

PMID- 7716891
TI  - [Results of induction therapy in newly diagnosed acute myeloid leukemias in study
      911 at the Institute of Hematology and Blood Transfusion].
AB  - Thirty-seven patients with de novo acute myeloid leukemias were admitted to the
      Institute of Hematology and Blood Transfusion in Prague in February 1991-December
      1993. Their age was 18-85 years with a median of 46 years. Two patients died on
      the day of admission, chemotherapy was initiated in 35 patients. Altogether 27
      patients (77%) achieved complete remission (CR), i.e. 18 (81%) of 22 patients
      younger than 55 years and 9 (70%) of 13 patients older than 55 years. Only 7
      (35%) of 20 patients achieved CR after a single therapy course 3/7 consisting of
      3 doses of daunorubicin 45 mg/m2 on days 1, 3, 5 and cytosine arabinoside 150-200
      mg/m2 every 12 hours for 7 days. However, 8 (61%) of 13 patients achieved CR
      after a single treatment course 4/7 with 4 doses of daunorubicin 45 mg/m2 on days
      1, 3, 5, 7 and identical doses of cytosine arabinoside as in the 3/7 treatment.
      We used the course with 10 high-doses of cytosine arabinoside 2000 mg/m2 every 12
      hours and daunorubicin 45 mg/m2 on days 4 and 5 (treatment HDAC/DNR) as the 1st,
      2nd or 3rd induction therapy in 12 patients and 9 (75%) of them achieved CR. The
      treatment was associated with a high toxicity. An intensified therapy 3/7h
      similar to the 3/7 one but with the doubled dose of cytosine arabinoside 300-400
      mg/m2 on days 5-7 was given to 5 patients as the 2nd induction but it did not
      improve the CR rate and it was associated with a high toxicity similar to the
      HDAC/DNR therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7716892
TI  - [Colorectal polyps and their endoscopic therapy].

PMID- 7716893
TI  - [A 2-month period of physical training in insulin-dependent diabetics].
AB  - Twenty type 1 diabetics participated after previous individual instructions in a
      8-week physical training programme. The latter comprised three training units per
      week. One training unit started by 10-minute warming up exercise, then the
      patients pedalled on a bicycle ergometer 2 x 10 minutes with a 5-minute break
      with a load amounting to 80% of the oxygen consumption during the maximum
      tolerated load. The final part was formed by swimming in a swimming pool,
      covering a distance of at least 200 m. After the termination of the programme the
      authors did not observe significant changes in the carbohydrate and lipid
      metabolism nor in physical performance, however, the maximal oxygen consumption
      increased as a result of training by 17% and the maximum achieved load by 25 W
      (i.e. one step). Throughout the investigation period the authors did not record
      any serious complications. The patients enjoyed the physical activity and
      reported improvement of the quality of life. Therefore the authors recommend
      physical training in the treatment of insulin-dependent diabetic patients.

PMID- 7716894
TI  - [The sleep apnea syndrome in patients with acromegaly].
AB  - The authors examined 19 nonselected patients with acromegaly (8 women and 11
      men), incl. 16 where the disease was hormonally active, 3 had normal growth
      hormone values, 11 patients had a surgical operation of the pituitary. The
      examination was made by the MESAM 4 method (all-night recording of the heart
      rate, respiratory sounds, body position and arterial oxygen blood saturation).
      The sleep apnoea syndrome was diagnosed in 10 patients (52.6%). In patients where
      the sleep apnoea syndrome was not confirmed by MESAM 4, so-called intermittent
      snoring was found, an indirect sign of impaired ventilation during sleep.

PMID- 7716895
TI  - [Cushing's syndrome in pregnancy].
AB  - Active Cushing's syndrome during pregnancy is a rare phenomenon which was so far
      described in the literature only in 85 women. The authors give an account of a
      patient who developed Cushing's syndrome during pregnancy and who was delivered
      during the eighth month of a healthy foetus by caesarean section, afterwards the
      hypercortisolism associated with hyperaldosteronism was treated by dextrolateral
      adrenalectomy. In the removed adrenal gland was a cortical adenoma made up of
      clear cells and cells reminding of the zona glomerulosa. Subsequently the authors
      summarize data from the literature on the prevalence of different pathogenetic
      forms of Cushing's syndrome in pregnant women, on the influence of
      hypercortisolism on mother and foetus, on the optimal diagnosis and therapy of
      this syndrome during pregnancy.

PMID- 7716896
TI  - [Endogenous digoxin-like and ouabain-like substances].
AB  - Despite the fact that cardioglycosides have been used in the treatment of cardiac
      failure for more than 2000 years, endogenous digoxin and ouabain-like substances
      were identified from the chemical aspect only in 1990. They are steroids, their
      main site of origin being the adrenals. It is assumed that they play a part in
      the regulation of the body fluids and sodium in the organism and participate in
      the regulation of cardiac activity. The stimulus which leads to their release
      into the blood stream are above all conditions associated with sodium and fluid
      retention with expansion of the intravascular volume. It is assumed that these
      substances participate in the pathogenesis of some types of hypertension. The
      authors present a general review of contemporary knowledge of endogenous digoxin
      and ouabain-like substances.

PMID- 7716897
TI  - [Stress tests in chronic heart failure].
AB  - The authors compared two types of spiroergometric tests in 14 patients with
      chronic heart failure (NYHA II-III, ejection fraction < 40%). Test A: 0.25 W/kg 3
      minutes, 1 minute break, increase by 0.25 W/kg a 3 minutes. Test B: 25 W 2
      minutes without break, increase by 10 W a 2 minutes. The two tests did not differ
      as to the achieved heart rate, blood pressure reading, oxygen consumption and
      biochemical parameters at the end of the load, even at the level of the anaerobic
      threshold. There was a significant statistical difference in the duration of the
      load: test A lasted 16.4 minutes, test B 9.7 minutes (p < 0.001). The length of
      the test B correlated with the peak oxygen consumption per 1 kg body weight (p <
      0.001, r 0.9866). The authors recommend for common practice test B with a defined
      period of the load as sufficient.

PMID- 7716898
TI  - [Virological institutions of the Russian Academy of Medical Sciences (on the 50th
      anniversary of the Academy)].

PMID- 7716899
TI  - [The problem of Vilyui encephalomyelitis].

PMID- 7716900
TI  - [Immunogenicity of attenuated reassortants of influenza A virus
      /Leningrad/134/47/57 (H2N2) for mice, depending on their genome].
AB  - Reassortants of cold-adapted strain A/Leningrad/134/47/57 (H2N2) and virulent
      strain A/PR/8/34 (H1N1), modeling genomic composition of vaccinal strains, were
      tried in mouse experiments. Reassortants' genomes included the major part (5, 6,
      or 7) from cold-adapted strain and 1 to 3 genes of virulent strain. All the
      tested reassortants did not differ by temperature sensitivity or cold adaptation
      phenotypes, did not cause the death of mice, but differed by the level of
      reproduction in murine lungs and by immunogenicity. Strains with genomic formulas
      6/2 (HA and NA of a virulent strain) and 5/3 (M) (HA, NA, and M of a virulent
      strain) were characterized by the highest immunogenicity. Reassortants including,
      besides HA and NA, PA gene 5/3 (PA) or inheriting only HA gene from strain
      A/pr/8/34 (H1N1) were hyperattenuated and low immunogenic.

PMID- 7716901
TI  - [The NS gene--a possible determinant of apathogenicity of a cold-adapted donor of
      attenuation A /Leningrad/134/47/57 and its reassortants].
AB  - Phenotypical properties of single-gene reassortants of attenuated cold-adapted
      strain A/Leningrad/135/47/57 (H2N2) and strain A/PR8/34 virulent for laboratory
      animals were studied. Only the group of reassortants inheriting NS gene from cold
      adapted virus was fully attenuated for various animals species, similarly as
      reassortants with 6/2 genomic formula containing all the 6 internal protein genes
      from strain A/Leningrad/134/47/57. Reassortant 25A-1 single-gene for NS was
      temperature-sensitive (ts) on mammalian cells but formed plaques at 40 degrees C
      on chicken kidney cells. Reassortants with genomic formula 6/2 were temperature
      sensitive in all types of cells used. Reassortant 25A-1 could synthesize normal
      amounts of polypeptides in MDCK cells at 39 degrees C, whereas protein synthesis
      of reassortants with 6/2 genomic formula was noticeably reduced at this
      temperature. Hence, a similar level of attenuation of both reassortant groups
      appears to be due to various molecular mechanisms. Possible role of NS2 gene
      mutation in attenuation of strain A/Leningrad/134/47/57 and its reassortants is
      discussed.

PMID- 7716902
TI  - [Biological properties and antigenic interconnection between Tiuleniy and Karshi
      flaviviruses].
AB  - Biological properties of flaviviruses Tyuleny and Karshi, new for the science,
      were studied. The viruses are highly pathogenic for laboratory animals; they
      replicate fairly well in primary chick embryo cells and PS cells. BHK-21 cells
      were found susceptible to replication of Karshi virus. Tyuleny and Karshi viruses
      were found capable of initiating and maintaining a persistent infection in
      primary brain cell cultures from suckling Syrian hamsters for at least 3 months.
      Both the viruses showed cytoproliferative activity in respect of the above cells
      in tissue cultures. Our data indicate that Tyuleny virus, a member of a separate
      antigenic group, is more closely related to Japanese encephalitis virus (strain
      JaGar 01), and Karshi virus to Powassan virus.

PMID- 7716904
TI  - [Use of monoclonal antibodies for detecting Aujeszky's disease virus in culture
      media by an immunoenzyme method].
AB  - Three modifications of quantitative enzyme immunoassay (EIA) for assessment of
      Aujeszky's disease virus (ADV) in culture medium are compared, in which
      monoclonal antibodies (MAB) to ADV GH glycoprotein were used: nonconcurrent two
      site "sandwich" EIA on the basis of two different MABs, indirect concurrent EIA,
      and direct concurrent EIA. MABs fit best of all for use in every of EIA
      modifications were selected. Conditions of the assays were optimized. Concurrent
      EIAs were 10-20 times less sensitive than sandwich EIA. The developed sandwich
      EIA permitted ADV assay in preparations of both live and formaldehyde-inactivated
      virus.

PMID- 7716903
TI  - [Further study of experimental hepatitis E in piglets].
AB  - Experimental infection of piglets with a fecal pool containing hepatitis E virus
      (HEV) strains Osh-25 and Osh-228 confirmed previous results obtained with HEV
      strain Osh-205 on susceptibility of these animals to hepatitis E. A biphasic
      increase of transaminase activities, histopathologic changes in the liver, virus
      excretion with feces were observed in the animals. The genome of viral particles
      in piglet feces conformed, at least partially, to human HEV RNA. Ultrastructural
      abnormalities of piglet hepatocytes resembled those in primates with experimental
      hepatitis E. The number of positive results (during follow-up of the particles
      and HEV RNA in various organs of experimental animals) was the highest on day 10
      after infection. Both the particles and HEV RNA were present in the lymphoid
      tissue over the entire follow-up period, from day 5 to day 15 postinfection.

PMID- 7716905
TI  - [Marburg virus and mononuclear phagocytes: study of interactions].
AB  - Interactions of Marburg virus and mononuclear phagocytes of guinea pigs were
      studied using a complex of virologic methods and electron microscopy. Active
      reproduction of Marburg virus in peritoneal macrophages both in vitro and in vivo
      was revealed. The study showed that mononuclear phagocytes were the first target
      cells in guinea pigs intraperitoneally infected with Marburg virus which provided
      virus dissemination into interstitial tissue of viscera. Analysis of the results
      indicates an important role of viral alteration of mononuclear phagocytes in the
      pathogenesis of Marburg disease.

PMID- 7716906
TI  - [Can chronic hepatitis B patients overcome resistance to antiviral therapy due to
      production of antibodies to recombinant alpha-2-interferon?].
AB  - Virologic screening helped single out a group of 25 patients with chronic
      hepatitis B not responding to antiviral therapy with recombinant interferon, with
      persistence of HBeAg and HBV DNA in the blood sera. Enzyme immunoassay revealed
      in 7 of them antibodies to alpha 2-interferon (anti-IF). To reduce anti-IF
      production, preliminary immunosuppressive therapy with azathioprine (100 mg) and
      prednisolone (40 mg daily) with gradual decrease of the dose and discontinuation
      of therapy by the end of the 4th week was carried out. Then a course of antiviral
      therapy with IF in dose 4 min U i.m. every other day was carried out, total dose
      per course being at least 100 min U. In 2 of the 4 patients administered a
      complete course of immunosuppressive and antiviral therapy anti-IF, HBeAg, anti
      HBc IgM, receptor to polymerized human serum albumin, and HBV DNA were no longer
      detected. If anti-IF still persisted after a course of immunosuppressive therapy,
      subsequent antiviral treatment did not influence the level of virus replication.
      Patients responding to therapy by elimination of HBeAg and HBV DNA had much lower
      titers of HBeAg and lower concentration of HBV DNA. The initial level of anti-IF
      was not related to the pattern of response.

PMID- 7716907
TI  - [Characteristics of neurovirulence, stability, and immunogenicity of attenuated
      variants of TP-21 Langat virus].
AB  - Clones of Langat TP-21 virus with neurovirulence for primates much lower than
      that of Elantsev 15-20/3 strain may be obtained by threshold dilutions method on
      mice. Neurovirulence for monkeys of L1-L5 clones of Langat TP-21 virus obtained
      at our laboratory was similar to neurovirulence of A.Sabin's type III vaccinal
      poliomyelitis virus. Attenuated clones of Langat virus are stable and retain
      protective properties in experiments with mouse protection from pathogenic
      viruses of tick-borne encephalitis complex.

PMID- 7716908
TI  - [Activation of viral reproduction in a mixed infection with human
      immunodeficiency virus and herpes viruses].
AB  - Mutual activation of reproduction of type 1 HIV and herpes simplex types 1 and 2
      viruses (HSV) was observed in simultaneous infection of continuous T-cellular
      lymphoblastoid lines (CEM, 119, Hut-78, MT-4, Jurkat-tat) and U-937 monocytic
      line. Syncytium formation and cytodestructive pattern of reproduction of viruses
      of both families in these cell lines necessitated the use of enzyme immunoassay
      (EIA) to detect the antigens of these viruses in order to assess the level of
      reproduction. The concentration of HIV antigens in EIA increased in mixed
      infection by 1.4 to 2.1 times in different cultures in comparison with the
      culture infected with HIV-1 alone, and concentrations of HSV-1 and HSV-2
      increased by 1.3-1.8 times in mixed infection, in comparison with reproduction in
      lymphoblastoid cultures infected with HSV alone. EIA was alone used to examine
      the production of IgG and IgM antibodies to Epstein-Barr virus, another
      representative of Herpesviridae family, in the blood sera of patients with
      immunodeficiency states in whose sera antibodies to proteins produced by gag HIV
      gene (p15/17, p24, p55) were detected. Increased concentration of IgG antibodies
      were revealed in 36% of these patients, whereas in healthy donors the sera with
      elevated concentrations of IgG to Epstein-Barr virus were far less incident
      (12%). A hypothesis about mutual activation of HIV and herpes viruses is put
      forward.

PMID- 7716910
TI  - [Composition and immunochemical properties of goat immunoglobulins against the
      Ebola virus].
AB  - Serum samples containing Ebola Virus neutralizing antibodies were prepared by
      prolonged immunization of goats with 10% liver homogenate from guinea pigs
      infected with Ebola virus. Differences in IgG fractions of normal and hyperimmune
      caprine blood sera were detected. Analytical chromatography on Polysil SA and
      immunodiffusion showed the presence of three IgG-containing fractions in
      hyperimmune sera. Immunochemical properties of these fractions were studied by
      solid-phase enzyme immunoassay and neutralization test. Antibodies to viral
      antigens were referred to IgG2 and IgG1a, and virus neutralizing properties were
      found mainly in IgG2 antibodies. Immunoglobulins were isolated from hyperimmune
      serum by alcohol sedimentation. The principal IgG fraction was found to contain
      much lower levels of antibodies to guinea pig liver antigens than intact serum,
      but at the same time it was characterized by a higher neutralization index.

PMID- 7716909
TI  - [Risk of infection with hepatitis B and C viruses of medical workers, patients in
      the hemodialysis ward, and vaccine prophylaxis of hepatitis B infection in these
      populations].
AB  - Markers of hepatitis B (HBsAg, anti-HBs) and C (anti-HCV) were detected in 1990
      1992 by enzyme immunoassay in 1581 medical workers, 230 last-year students of
      medical schools, 269 patients hospitalized at hemoperfusion wards, and 701 blood
      donors. Hepatitis B markers were detected in medical workers two times more
      frequently than in donors (HBsAg in 4.7 and 2.2% of these, respectively, anti-HBs
      in 26.2 and 14.0%), and anti-HCV were found almost three times more frequently
      (in 3.1 and 1.1%, respectively). The incidence of these markers in students of
      medical schools was the same as in donors. Hepatitis B markers (HBsAg, anti-HBs)
      were detected in 39.0% of patients of hemoperfusion departments, HBsAg being
      present in 11.9%, and antiHCV in 25%. A direct relationship was revealed between
      the incidence of hepatitis B and C markers and duration of treatment at dialysis
      centers or length of service at therapeutic institutions. Three vaccinations with
      Engerix B 944 vaccine were administered to 944 medical workers and 162 medical
      students and four vaccinations in double doses to 40 patients of hemoperfusion
      centers who had no hepatitis B markers; a month after immunization anti-HBs in
      protective titers were detected in 91.4, 93.9, and 76.1% of them, respectively,
      and a year after vaccination these values were 77.2, 82.5, and 53.3%. No cases of
      hepatitis B, detection of HBsAg, or postvaccination complications in the vaccines
      were recorded.

PMID- 7716911
TI  - [Antiviral effect of various oligonucleotide derivatives, complementary to tick
      born encephalitis virus RNA].
AB  - Antiviral effect of two nucleotides complementary to tick-borne encephalitis
      (TBE) virus genome and their derivatives was compared to that of noncomplementary
      oligonucleotides. All the tested reagents influenced TBE multiplication in cell
      culture, this manifesting by various degrees of suppression of the cytopathic
      effect of the virus. Intact oligonucleotides, both complementary and
      noncomplementary to TBE, reduced virus titer by 2-4 orders, whatever the
      concentration of oligonucleotide. In some experiments a higher virus-inhibiting
      effect of complementary oligonucleotides (by 3-4 orders) was observed vs.
      noncomplementary (by 1-2 orders). Moreover, different oligonucleotide derivatives
      suppressed virus multiplication in porcine embryo kidney cell culture. In
      parallel with investigation of virus-inhibitory effect of oligonucleotides in
      cell culture, their effects on the synthesis of virus-specific and cellular
      proteins was studied. Screening of oligonucleotide derivatives by capacity to
      suppress biosynthesis and multiplication of virus in cell culture showed the
      highest efficacy of reaction-capable and cholesterol derivatives.

PMID- 7716912
TI  - [A method of preparing antibody erythrocytic diagnostic means for detecting
      viruses].
AB  - It was found possible to use method for preparation of antibody erythrocytic
      diagnosticums for detection of agents of influenza and arboviral infections. Test
      systems prepared by the developed method were superior in sensitivity to
      immunoreagents prepared with previously proposed amidol. Testing of 1387 tick
      samples collected in various climatic geographical zones of the Republic of
      Kazakhstan detected arboviral antigens in 4.61% of cases. The highest share of
      positive results was observed with diagnostic agents for detection of Syrdarya
      valley fever and Sindbis viruses (37:5 and 32.81%, respectively).

PMID- 7716913
TI  - [A nonisotopic method of quantitative PCR analysis in diagnosing HIV infection].
AB  - A nonisotopic method for the detection of HIV DNA has been developed, based on
      the use of avidin-biotin complex to identify the products of polymerase chain
      reaction (PCR). Biotin label integrated in deoxyuridine triphosphate (bio-11
      dUTP) was incorporated in the structure of amplified fragments in the course of
      PCR. The resultant products were identified in hybridization reaction with
      specific HIV DNA adsorbed on polystyrene plates. The suggested method was not
      inferior to the traditional radioisotope method in sensitivity and specificity
      and helped quantitatively assess the results of experiments using an objective
      criterion--optic density value.

PMID- 7716914
TI  - [Selection of primers and their use in the polymerase chain reaction for
      diagnosing infections caused by herpes simplex virus and cytomegalovirus].
AB  - The authors present the results of studies on the construction of highly
      sensitive primers for rapid diagnosis of infections caused by Herpes simplex
      virus (HSV) and cytomegalovirus. An oligonucleotide primer to HSV-1 is described,
      which permits detection of HSV-1 DNA in infected cultures and in clinical
      material in dilution 10(-7), whereas the "universal" primer constructed on the
      basis of published data detects both HSV-1 and HSV-2 only in dilution 10(-4).
      Study of the clinical material in polymerase chain reaction (PCR) vs. virus
      isolation in infected cell cultures permitted us assess the diagnostic value of
      this reaction with the constructed primers as high. Use of two pairs of primers
      (those designed to HSV-1 and the "universal") permitted a differential diagnosis
      in the PCR between HSV-1 and HSV-2 in clinical material. Highly specific
      oligonucleotide primers were designed for the rapid diagnosis of cytomegaloviral
      infection, and clinical material was investigated making use of these primers.

PMID- 7716915
TI  - [Laboratory criteria for assessing the safety of candidate strains for live
      vaccines against tick-borne encephalitis].
AB  - The authors present the results of studies on the construction of highly
      sensitive primers for rapid diagnosis of infections caused by Herpes simplex
      virus (HSV) and cytomegalovirus. An oligonucleotide primer to HSV-1 is described,
      which permits detection of HSV-1 DNA in infected cultures and in clinical
      material in dilution 10(-7), whereas the "universal" primer constructed on the
      basis of published data detects both HSV-1 and HSV-2 only in dilution 10(-4).
      Study of the clinical material in polymerase chain reaction (PCR) vs. virus
      isolation in infected cell cultures permitted us assess the diagnostic value of
      this reaction with the constructed primers as high. Use of two pairs of primers
      (those designed to HSV-1 and the "universal") permitted a differential diagnosis
      in the PCR between HSV-1 and HSV-2 in clinical material. Highly specific
      oligonucleotide primers were designed for the rapid diagnosis of cytomegaloviral
      infection, and clinical material was investigated making use of these primers.

PMID- 7716916
TI  - [Amplification of the activity of HIV-1 isolates purified from seropositive
      children after cryopreservation of persistently-infected cells].
AB  - HIV-1 strains MC-1974 and MC-1978 were isolated from children infected in
      hospital. Both children presented with symptoms of HIV infection by the moment
      the blood samples for virus isolation were collected. In vitro the isolated
      strains showed weak infective activity and caused no cytopathic effect in
      sensitive cells. It may be explained by azidothymidine antiviral therapy or by
      initial immunodeficient status of both children not caused by HIV infection.
      Virus activity was enhanced in both cultures after reactivation of Jurkat-tat
      cells persistently infected with MC-1974 and MC-1978 strains after
      cryopreservation. Viruses isolated from culture fluid effectively infected Jurkat
      tat cells. The infection was associated with formation of syncytia, accumulation
      of viral particles detected by electron microscopy and of intracellular antigens
      detected by fluorescent antibody technique and by immunoblotting. The results
      suggest the presence in the body of infected children and in Jurkat-tat-1974 and
      Jurkat-tat-1978 persistent lines of a viral genome containing all virusspecific
      genes necessary for productive expression of HIV-1.

PMID- 7716917
TI  - [Isolation of purified Ebola virus].
AB  - Purified concentrates of Ebola virus were prepared by two methods, adsorption on
      polyethylenglycol-600 followed by ultracentrifugation in sucrose density gradient
      and ultrafiltration. The ultrafiltration method permits preparation of
      concentrated Ebola virus with better preserved virion structure and infective
      activity than the traditional method.

PMID- 7716918
TI  - [Results of serologic screening for hemorrhagic fever with kidney syndrome in
      Moldova].
AB  - Results of serologic screening of small mammals for antigen of the virus of
      hemorrhagic fever with the renal syndrome (HFRS) and of testing human sera for
      antibodies to this virus in Moldova are reviewed. A total of 9946 animals
      belonging to 22 species and blood sera of 792 healthy donors were examined in
      1983-1990. HFRS virus antigen was detected in 30 animals of 9 species, with the
      highest incidence of the antigen in gray voles. Two serotypes of Hantavirus were
      found to circulate in small mammals: Puumala and Hantaan. Screening of healthy
      humans revealed antibodies to HFRS virus in 7.8%. Natural foci of HFRS were
      detected in 23 of the 44 administrative territories of the Republic situated in 5
      landscape geographical provinces.

PMID- 7716919
TI  - [Duration of detection of influenza virus markers in human blood lymphocytes].

PMID- 7716920
TI  - [Isolation of human cytomegalovirus in primary cytomegalic infection].
AB  - Cytomegalovirus was isolated from a patient with generalized cytomegaloviral
      infection. The strain was identified using tissue culture method, electron
      microscopy, and serologic tests. The virus was repeatedly passed in diploid human
      fibroblast cells and recorded as Vesna human cytomegalovirus strain.

PMID- 7716921
TI  - [Study of the anti-HIV activity of miramistin].
AB  - The anti-HIV activity of a cationic detergent myramistin and nonionic detergent
      dezintegron-0 (d-0) was studied using HIV-1 strains III B/H9 and BRU in
      lymphoblastoid cells MT-4 and Jurkat-tat. Myramistin in a concentration of 0.075
      mg/ml was shown to prevent HIV-1 replication in MT-4 when these cells were
      cocultivated with the cells preinfected and treated with the detergent.
      Myramistin in concentrations from 0.030 to 0.050 mg/ml delayed the accumulation
      of virus antigens in the cells by 4 and 14 days, respectively, without preventing
      the infection of intact cells. Nonionic d-0 prevented HIV-1 infection of intact
      Jurkat-tat cells at a concentration of 12.5 mg/ml.

PMID- 7716922
TI  - [Isolation of human B-cells, specific for viral peptides, using magnetic
      spheres].
AB  - A method for isolation of human B cells specific to viral peptides using magnetic
      beads has been developed. The method was used for the isolation from human
      tonsils of B cells specific to HIV-1 gp 120 MN-24 peptide (residues 302-322) and
      to Epstein-Barr virus 107 EBNA-1 peptide. The cells selected with beads were
      transformed by Epstein-Barr virus. The resultant cell cultures produce human
      immunoglobulin antibodies to HIV-1 MN-24 and to Epstein-Barr EBNA-1 p107
      peptides.

PMID- 7716923
TI  - [Pseudosuspended cultured cells for obtaining influenza A and B viral antigens].
AB  - Conditions for pseudosuspension culturing of continuous cells of the kidneys of
      dogs (MDCK), green marmosets (CV-1), and swine (SPEV) on two types of
      microcarriers (Cytogel-3 and cytolar-2) under semiproduction conditions (50 liter
      bioreactor) were developed on a model of reassortants of influenza viruses A and
      B. To standardize the conditions, native sera were replaced by growth-stimulating
      proteins isolated from the sera of various animals (cattle, northern deer,
      swine). A better adhesive capacity and more active cell proliferation on porous
      microcarrier cytogel-3 were observed. The highest proliferative activity of cells
      was observed when porcine growth-stimulating proteins were used. Influenza A
      virus reassortant (H3N1) was actively reproduced in MDCK cells. The reproduction
      of influenza B virus reassortant was similarly higher in MDCK cells, in
      comparison with SPEV cells; at the same time, no differences in hemagglutinin
      titers in the two cell cultures were observed. The pseudosuspension method of
      cell culturing is recommended for the preparation of influenza antigens.

PMID- 7716924
TI  - [Use of an immunoenzyme method for diagnosing canine distemper].
AB  - Analysis of the clinical data and laboratory studies brought the authors to a
      conclusion on the possibility of using dot solid-phase ELISA on nitrocellulose
      for rapid (1 h), simple, and specific detection of canine distemper virus. The
      method is sufficiently specific, helps specify the clinical diagnosis, and may be
      used in future for the creation of a commercial test system.

PMID- 7716925
TI  - [Glycoproteins from the African swine fever virus].
AB  - The composition of African swine fever virus (ASFV) glycoproteins was studied.
      Isolate-specific major gp 110-140 was identified by radioimmunoprecipitation in
      lysate of porcine bone marrow cells infected with hemadsorbing virus strains.
      Carbohydrates constitute about 50% of the total mass of gp 110-140. A
      quantitative method is proposed for identification of the serologic relationships
      between ASFV hemadsorbing strains. A possible role of ASFV glycoprotein
      carbohydrates in the hemadsorption, virulence, and immunogenicity is discussed.

PMID- 7716926
TI  - [The effect of fetal calf serum on the anti-HIV properties of miramistin].
AB  - The anti-HIV activity of an antiseptic miramistin in the presence of fetal calf
      serum (FCS) was studied. It has been recently shown that cation detergent
      miramistin at a concentration of 100 micrograms/ml prevented HIV-1 replication in
      MT-4 cells when these cells were cocultivated with MT-4 cells previously infected
      and treated with the detergent in a protein-free medium. Under such conditions 50
      micrograms of miramistin per ml delayed HIV propagation in MT-4 cells by 14 days.
      Detergent-dependent arrest of HIV development was abolished by addition of FCS at
      a final concentration of 50%. Miramistin in a dose of 100 micrograms/ml prevents
      HIV-1 replication in Jurkat-tat cells when they are cocultivated with the cells
      of the same line previously infected and treated by the detergent in the presence
      of 5% FCS. FCS in concentrations from 12.5 to 75% prevents the anti-HIV activity
      of miramistin in a dose of 100 micrograms/ml.

PMID- 7716927
TI  - [Use of collase for culturing cells].
AB  - Collase, an enzymatic preparation made from crab hepatopancreas, was used as a
      dissociative reagent in preparation of primary cell cultures and for detachment
      of continuous cells from the substrate during reinoculation. Collase was found to
      increase viable cell harvest by 2 to 2.5 times in comparison with trypsin and had
      a less detrimental effect on the cells which retained their proliferative
      activity, morphology, productivity, and sensitivity to viruses.

PMID- 7716928
TI  - [Preparation of rabbit antiserum to Ebola virus].
AB  - Humoral immunity of rabbits insusceptible to Ebola virus infection were studied
      after challenge with infectious Ebola virus and inactivated antigen of this
      virus. Administration of Ebola virus antigen induced the production of specific
      antibodies in proportion with the antigen dose injected.

PMID- 7716929
TI  - [Assessment of bioavailability of magnesium preparations].
AB  - The bioavailability was studied of three magnesium preparations-Asmag, Slow-Mag
      and magnesium oxide (wafer)-administered to healthy volunteers for two weeks. The
      observed increase of magnesium level in the serum was not statistically
      significant.

PMID- 7716930
TI  - [Modern possibilities of preventing postoperative goiter recurrence].
AB  - The authors present an analysis of the material of 84 patients operated on in the
      years 1979-1992 for non-malignant recurrent goitre. The method of management and
      treatment results are presented. The schema of management is also described in
      prevention of goitre recurrences, involving correctly performed operation,
      periodical control examination, and routine postoperative administration of
      thyroid preparations. The use of hormonal prophylaxis (L-Thyroxin) in suppressive
      doses, under TSH control seems to have a significant influence on the reduction
      of the number of recurrences.

PMID- 7716931
TI  - [Evaluation of granulocytes in children with malnutrition].
AB  - In 29 infants with II and III degree of undernutrition, the studies were
      performed of the granulocyte system including: the number of granulocytes in the
      bone marrow reserve pool, circulating pool, parietal and total peripheral blood,
      phagocytosis evaluation, NBT test and the activity of granulocytic enzymes
      alkaline phosphatase and peroxidase. The following deviations were found in
      comparison to children of the same age with normal body weight: 1. Significant
      decrease of the reserve granulocyte pool in the bone marrow in children with
      considerable undernutrition, reaching the value of bone marrow reserve in
      newborn. 2. Increase of phagocytic activity of granulocyte in children with
      undernutrition, and increased readiness of these cells to intracellular killing.
      3. Normal activity of alkaline phosphatase in granulocytes, increased peroxidase
      activity during the period of considerable undernutrition.

PMID- 7716933
TI  - [Recurrent abdominal pain in children].
AB  - The purpose of the work was an analysis of the causes of recurrent abdominal pain
      in children treated in the Paediatric Department, Province Hospital in Rzeszow in
      the years 1975-1991. The analysis included 3480 children (59.3% girls and 40.7%
      boys) aged 6-16 years. The causes of recurrent abdominal pain were
      gastrointestinal tract diseases (45.7%), urinary system diseases (36.8%), extra
      abdominal diseases (6.4%), psychogenic background (11%).

PMID- 7716932
TI  - [Can TNF-alpha and IL-6 be helpful in assessment of chronic hepatitis in
      children?].
AB  - The purpose of the work was an assessment of TNF-alpha and Il-6 concentrations in
      34 children with diagnosed chronic hepatitis. In all studied patients the values
      of TNF-alpha and Il-6 concentration were slightly increased. The correlations
      calculated between TNF-alpha and Il-6 concentrations calculated between TNF-alpha
      and Il-6 concentrations and laboratory parameters (laboratory indicators of
      hepatitis activity--AlAT; liver function indicators--prothrombin index, bilirubin
      concentration, bile acid concentration, alkaline phosphatase activity, anti-pyrin
      half-life) were non-significant in Spearman non-parametric test (p > 0.005)
      except for the correlation between albumin and TNF-alpha concentrations. No
      statistically significant differences of TNF-alpha and Il-6 concentrations were
      found between groups of patients with active and persistent hepatitis; groups
      with and without cirrhosis as well as between groups with and without portal
      hypertension. Normal or slightly increased TNF-alpha and Il-6 concentrations,
      observed in chronic hepatitis in children should be explained by compensated
      liver function in such patients.

PMID- 7716934
TI  - [Changes in ECG examination of patients with trichinosis].
AB  - In the years 1963-1992, 560 patients with the diagnosis of trichinosis were
      treated in the Department of Parasitic Diseases and Neuroinfections, including
      310 women (55.3%) and 250 men (44.7%) aged from 6 to 75 years. Out of this number
      of patients in 59 cases (10.5%) myocardial damage was found in the course of the
      disease. The most frequently found changes in ECG record were ventricular
      repolarization disturbances (66.1%) which persisted in 18.6% of cases before
      discharge from the hospital. Depolarization disturbances accounted for 32.2% of
      cases and persisted before discharge from the hospital in 10.1% of patients. In
      6.7% of patients, persistence of pathological ECG record was found during the 4th
      month after the hospitalization which may be an evidence of prolongation of the
      inflammatory process within the myocardium.

PMID- 7716935
TI  - [Effect of CO2 insufflation into the peritoneal cavity on selected indices of
      respiratory system function during laparoscopic cholecystectomy].
AB  - An attempt was undertaken at evaluation of the influence of CO2 insufflation in
      patients subjected to laparoscopic cholecystectomy on pulmonary dynamic
      compliance, pulmonary resistance, pressures in the airways, CO2 pressure in
      expired air, and arterialized blood gas analysis. The studies were carried out in
      a group of 33 patients, including 26 women and 7 men, evaluated according to ASA
      scale as I/II degrees. The means of the values obtained before CO2 insufflation
      into the peritoneal cavity were compared with the means from the period of
      pneumoperitoneum maintenance. Statistically significant decrease of pulmonary
      compliance, increase of the mean pressure in the airways and increase of CO2
      pressure both in expired air and arterialized blood were demonstrated. Pulmonary
      resistance and oxygen pressure in blood remained without statistically
      significant changes. The attention was paid to the rationale of including
      capnometry to the standard monitoring equipment during laparoscopic operations.

PMID- 7716936
TI  - [Effect of age on dynamics of fear in patients undergoing cholecystectomy].
AB  - Forty patients, hospitalized in order to undergo the planned cholecystectomy were
      investigated with the help of self-evaluation questionnaire after Spielberger et
      al. The patients were divided according to the age, into two groups, each of them
      including 20 persons: Group I-13 women and 7 men above 60 (61-84) Group II-15
      women and 5 men below 60 (19-57) The patients filled the questionnaire two days
      before the operation as well as the day before going home. Preoperational
      examination did not show any significant differences in fear intensification
      between two groups. Fear did not also depend upon the sex of the patients.
      Significantly higher (p < 0.001) level of fear was noticed in Group I at the time
      of medical examination before going home. The reason is most probably the elderly
      people's uncertainty concerning their physical efficiency with in many cases is
      necessary for them to survive. The seniors are also afraid of both compulsory
      dieting and limiting their life activities.

PMID- 7716937
TI  - [Vaccine therapy in the treatment of nasal and sinus bacterial allergies].
AB  - An analysis was performed of the course of nasal and sinus bacterial allergy in
      160 children treated in the years 1981-1990 with bacterial vaccines. History
      data, results of medical examinations and laboratory investigations, indications
      and contraindications to vaccine therapy, and the methods and results of
      treatment are presented. Vaccines available in Poland were used--Polyvaccium
      (nasal and subcutaneous) produced by Biomed, Broncho-Vaxom, IRS-19. As the main
      criterion of positive results, improvement or regression of clinical
      manifestations, normalization of immunoglobulin level, and also extinction of
      organ reactions and generalized and local skin reactions to bacterial allergens,
      were accepted. Very good and good results were achieved in 63% of the studied
      patients. The best results were achieved using combined treatment--vaccine
      therapy, anti-inflammatory drugs, and symptomatic antiallergic treatment (68% of
      positive results). In comparison to the control group (80 children) in which no
      vaccine therapy was used, the results obtained in the studied group were
      statistically significantly better.

PMID- 7716938
TI  - [Analysis of orbital diseases].
AB  - Orbital diseases, in view of the special situation and anatomic structure of the
      orbit require greater attention and wide cooperation of doctors of many
      specialities, being an interdisciplinary problem. The analysis of the presented
      material showed that almost half the treated orbital diseases were bone fractures
      (48.4%), resulting mainly from traffic trauma (67.4%). The remaining diseases
      were orbital inflammations and tumours, and their numbers were similar. The fact
      is worth attention of decreasing number of orbital inflammations in successive
      years and increasing tendency for orbital tumour occurrence.

PMID- 7716939
TI  - [Results of surgical treatment of stress urinary incontinence in women in light
      of urethral flow studies].
AB  - Forty-six women are presented, aged from 38 to 62 years, treated surgically by
      Marshall-Marchetti-Krantz method for effort urinary incontinence. The
      postoperative results were subjected to analysis and their objective value was
      assessed by carried out uroflowmetric studies. The necessity of uroflowmetry
      before starting the operation was assessed.

PMID- 7716941
TI  - [Capsaicin in pain therapy].
AB  - In the paper the possibilities of therapeutic use of capsaicin are presented.
      This drug seems to be very effective in neuralgia after zoster, and less
      effective in painful diabetic neuropathy. Attempts are also undertaken at its use
      in cluster headache, trigeminal neuralgia and arthralgia. Confirmation of the
      effectiveness of the discussed drug in these pain syndromes requires further
      studies.

PMID- 7716940
TI  - [Effect of hemodialysis using cuprophan and polysulfone dialyzers on rosette
      tests, concentration of immunoglobulins and complement components in serum of
      patients with chronic renal failure].
AB  - In 15 patients with chronic renal failure, the effect was studied of
      haemodialysis using cuprophan and polysulfone dialyzers on rosette tests, and the
      concentrations of immunoglobulins and C3c and C4 complement components in
      peripheral blood. It was found that the per cent of E and EAC rosettes decreases
      within 30 minutes of the procedure, IgG, IgA and IgM levels increase after 120
      minutes of the procedure, while the concentrations of C3c and C4 components are
      not changing significantly during haemodialysis using both types of the
      dialyzers. The authors found that the polysulfone membrane seemed not to be more
      biocompatible than the cuprophan one.

PMID- 7716942
TI  - [Transplantation of the small intestine in man].

PMID- 7716943
TI  - [Myocardial infarction as the first manifestation of bronchial tumor
      dissemination].
AB  - A case is described of bronchial cancer with metastases to the heart. The first
      manifestation of the disease was the occurrence of clinical and
      electrocardiographic features of myocardial infarction.

PMID- 7716944
TI  - [A case of Menetrier disease].

PMID- 7716945
TI  - [Syndrome of chronic intravascular coagulation in the course of chronic myeloid
      leukemia].
AB  - The syndrome of chronic intravascular coagulation occurs very often in the course
      of malignancies including leukaemias, however, it is not always diagnosed. Two
      cases are presented of chronic syndrome of intravascular coagulation in the
      course of chronic myeloid leukaemia; in one patient being in chronic phase and in
      other patient during blastic phase. In the first case the patient required only
      causative treatment of the basic disease, in the second case, apart from
      causative treatment of blastic phase, heparin administration, platelet mass and
      frozen plasma transfusion were necessary.

PMID- 7716946
TI  - [A case of kidney and ureter tuberculosis causing diagnostic difficulties].
AB  - A case is presented of tuberculosis of the kidney and ureter with negative
      bacteriological examination, suspected of malignant tumour. The diagnosis was
      based on histological examination of ureteral specimen taken intraoperatively.

PMID- 7716947
TI  - [Metastasis of clear cell renal cancer to the nose and nasal sinuses].
AB  - Metastases of malignant tumours of remote location to the nose and nasal sinuses
      are rare. The possibility of their occurrence should be, however, taken into
      account, since rhinological manifestations may precede the diagnosis of primary
      tumour. This is true especially in the case of clear-cell renal cancer whose
      metastases are the most frequently found secondary malignant tumours of the nose
      and nasal sinuses. A case is described of clear-cell renal cancer metastasis to
      the frontal sinus.

PMID- 7716948
TI  - [A ward supervisor from the Internal Medicine Department providing health
      services at the elementary school--does it still exist?].

PMID- 7716949
TI  - [Echocardiographic evaluation of left ventricular function in patients after
      myocardial infarction treated with enalapril].
AB  - The studies were carried out in 30 patients (24 men and six women) aged 40-56
      years, mean age 51 years after myocardial infarction in whom enalapril in doses 5
      10 mg daily, mean dose 8,5 mg daily was added to drugs used as yet. This drug was
      administered for six weeks. The patients had myocardial infarction 6-18 months
      before their inclusion to the studies. In all patients two-dimensional
      echocardiographic and Doppler examinations were performed twice: before and after
      the treatment with enalapril. Left ventricular contractility disturbances and the
      following parameters were analysed: maximal early diastolic filling rate (EDF),
      maximal late diastolic filling rate (LDF), EDF/LDF ratio and early diastolic
      deceleration time (dec. EDF) and early diastolic slope (EF sl.). Enalapril
      administered in patients after myocardial infarction caused an increase of
      ejection fraction and increase of the contractility of left ventricular muscle
      segments not involved by necrosis. It exerted, however, no effect on the changes
      of contractility index. After the treatment with enalapril the maximal late
      diastolic filling rate (LDF) was significantly decreased while early diastolic
      deceleration slope (EF sl.) was significantly increased. The observed influence
      of enalapril on the left ventricular filling profile may suggest an improvement
      of left ventricular diastolic function.

PMID- 7716950
TI  - [Assessment of hypolipemic action of the preparation olbetam in people with
      primary hypercholesterolemia].

PMID- 7716951
TI  - [Evaluation of arrhythmia in patients with acute myocardial infarction receiving
      neoton (phosphocreatine)].

PMID- 7716952
TI  - [Comparative assessment of digoxin and captopril in the treatment of chronic
      congestive circulatory failure, NYHA grade II].
AB  - In 42 patients aged 33 to 79 years (mean age 55 years) with NYHA grade II chronic
      congestive circulatory failure, a comparative assessment was carried out of the
      effectiveness of treatment with captopril (29 patients, daily dose 18.75-150 mg,
      mean 82.5 mg) adn digoxin (13 patients, daily dose 0.125-0.5 mg, mean 0.275 mg).
      The patients were administered the drugs, depending on the improvement obtained,
      for 3-5 weeks. In the assessment of the effectiveness of the treatment, the
      following was taken into account: medical examination, laboratory investigations,
      chest X-ray, exercise tests and haemodynamic parameters measured during 2D and M
      echocardiographic examination. In the group of patients treated with digoxin the
      following was observed: a significant, in comparison to the patients receiving
      captopril, reduction of the heart rate by 11 beats per minute, decrease of the
      heart volume index by 50 ml/m2 and increase of the stroke volume by 14 ml. Higher
      effectiveness of captopril was observed as increase of the maximal workload
      during exercise test by 21 W and prolongation of its duration by three minutes.
      It seems that captopril may find use also in the treatment of early stages of
      circulatory failure.

PMID- 7716953
TI  - [Biochemical evaluation of digoxin dosage in patients with heart failure].
AB  - The investigations were carried out in 56 patients aged 54 to 84 years, treated
      with a supporting dosage 0.25 mg of digoxin because of chronical insufficiency of
      the heart, according to the NYHA classification II and III degree, in whom the
      functions of liver and kidneys have not been ascertained. A fourfold
      determination of digoxin concentrations in the blood was established in the time
      of distribution balance. From among the examined patients three groups were
      separated: receiving the drug chronically at 8.00 a.m. (group A), receiving it at
      8.00 p.m. (group B) and group C, for which the sacral method was used. Depending
      on medical indications the patients received during the examination other drugs.
      In group C the therapy was limited to diuretic drugs. In no clinical symptoms of
      digitalism could be observed. Subtherapeutic levels of digoxin (< 0.8 ng/ml) were
      found in the three groups on an average in 50% of the patients. The high
      percentage of patients with nontherapeutic concentration in blood serum confirms
      once more, that treatment with digoxin without checking their concentration in
      the serum does not give the certainty of suitable dosage. The results of the
      studies show that the optimalization of digoxin therapy from the point of
      pharmacological view should be based on a penetrating estimation of the whole of
      the clinical image, the checking of the image with the help of the concentration
      determinations of the drug.

PMID- 7716954
TI  - [Effect of slow infusion of magnesium sulphate on changes of arterial blood
      pressure values in patients with ischemic heart disease].
AB  - In the paper the influence is presented of magnesium sulphate infusion on the
      changes of arterial blood pressure values in cases of initial hypertension and
      normotension in patients with coronary heart disease. Twenty-six patients were
      studied in this aspect, with precise measurement of arterial blood pressure by
      non-invasive method after careful preliminary qualification. The measurements
      were carried out during magnesium sulphate infusion by intravenous route. It was
      found that the magnesium sulphate infusion normalized arterial blood pressure in
      cases of initial hypertension while it failed to reduce the initial arterial
      blood pressure in cases of normotension.

PMID- 7716956
TI  - [Thoracoscopy].
AB  - The purpose of the work is presentation of own experience in the use of
      thoracoscopy in patients with pathological pleural changes. In the years 1989
      1991 in the Chair and Department of Pulmonology and Tuberculosis, Medical Academy
      in Gdansk, 20 thoracoscopies were performed with simultaneous taking of material
      for histopathological examination. In 15 patients from this group the diagnosis
      was made confirming the aetiology of pleural pathological changes. It should be
      stressed that in the group of patients with suspected malignancy, the diagnosis
      was confirmed in 100% of cases. Thoracoscopy is a useful diagnostic procedure
      during which aimed pleural biopsy may be performed.

PMID- 7716955
TI  - [Comparison of the effectiveness of olicard 40 retard and cardonit 40 prolongatum
      preparations in treatment of stable coronary heart disease].
AB  - The purpose of the work was a comparison of the effectiveness of representatives
      of two subgroups of nitrates: Olicard 40 (isosorbide mononitrate) and Cardonit 40
      (isosorbide dinitrate) in the treatment of ischaemic heart disease. The studied
      group consisted of 52 patients with stable coronary heart disease who were given
      for 30 days according to "blind trial" rules either Cardonit 40 or Olicard 40 in
      single daily dose. The effects of the treatment were monitored, assessing the
      parameters during three exercise tests and two 24-hour records by the Holter
      method. The advantage of Olicard 40 was demonstrated, expressed by higher
      effectiveness in the treatment of coronary heart disease (especially its "silent"
      form) without development of tachyphylaxis and with lower per cent of adverse
      reactions.

PMID- 7716957
TI  - [Results of treating endometriosis with nafarelin].
AB  - 50 women with endometriosis diagnosed during laparoscopy or laparotomy were given
      six months treatment of nafarelin 400 mcg/day. Before the treatment and after its
      completion endometriosis was classified according to the AFS scale. Symptom
      Severity Score numerical scale was also used. After the completion of nafarelin
      treatment a decrease in AFS scores from 19.6 to 10.2 was seen. The complete
      withdrawal of clinical symptoms was seen in 52% of patients, and partial
      withdrawal in 42% of patients. The mean of the Symptom Severity Scores
      (dysmenorrhoea, dyspareunia, lower abdominal pain and pelvic exam abnormalities)
      has decreased from 7.1 to 2.1 points which is a 70% decrease. These results show
      the high efficacy of nafarelin in endometriosis treatment.

PMID- 7716958
TI  - [False thrombocytopenia].
AB  - The causes of false thrombocytopenia may be: abnormal mixing of studied blood
      with anticoagulant, EDTA-dependent antibodies, satellite thrombocytes around
      leucocytes. Searching for false thrombocytopenia, thrombocyte count was examined
      in 477 children without signs of haemorrhagic diathesis. False thrombocytopenia
      was found in two patients.

PMID- 7716959
TI  - [Lead poisoning in children from the industrial region of Silesia--markers of
      chronic intoxication].
AB  - In the paper the degree of lead micro-intoxication was assessed in school
      children from the region of emissions of the Mining-Ironworks Complex "Boleslaw"
      in Bukowno. The study included 323 children of either sex aged from 7 to 14
      years. In these children the levels of selected lead intoxication markers were
      determined--concentration of zinc protoporphyrin (ZnPP) in the erythrocytes and
      concentration of delta-amino-laevulinic acid (ALA) in urine. The obtained results
      were compared with corresponding results in the control group which consisted of
      163 children of the same age, living in a control area without exposure to heavy
      metals. In the studied group in all age subgroups, significantly higher ALA
      concentrations in urine were observed in comparison to the control group. At the
      same time, exceeding of upper acceptable range of ALA concentration in the
      organism was five times more frequent in this group. On the other hand, the
      concentration of ZnPP in the erythrocytes failed to show any significant
      differences between the compared groups in any of the analysed age subgroups. On
      the basis of the obtained results it was demonstrated that the school children
      living in the region of emissions of the MIC "Boleslaw" had biochemical features
      of long-term lead microintoxication. As it seems, the concentration of ALA in
      urine is of greater diagnostic value in comparison to the concentration of ZnPP
      in the erythrocytes in screening examinations in these children.

PMID- 7716960
TI  - [Lead poisoning in children from the industrial region of Silesia--hematologic
      indices].
AB  - In the paper, the basic parameters of blood morphologic pattern were assessed in
      school children exposed to toxic heavy metal emission. The studies included 323
      children aged from 7 to 14 years, living in the region of emissions of the Mining
      Ironworks Complex "Boleslaw" in Bukowno. In these children haemoglobin
      concentration, haematocrit and erythrocyte and leucocyte counts were determined
      using routine laboratory tests. The obtained results were compared with
      corresponding results in the control group which consisted of 163 children of
      either sex living in a control region without exposure to heavy metals. In the
      studied group in most age subgroups significant decreases of erythrocyte count
      haemoglobin concentration and increases of haematocrit value were observed in
      comparison to the control group. At the same time, in these children, ten times
      higher, in relation to the control group, incidence was found of haemoglobin
      concentrations below 120 g/l, characteristic of anaemia. As it seems, one of
      important factors causing the decrease of the value of the parameters of blood
      morphologic pattern in the studied children is chronic microintoxication with
      lead, manifesting itself as significantly increased concentration of delta-amino
      laevulinic acid in urine which is a sensitive marker of this intoxication.

PMID- 7716961
TI  - [Modern laboratory diagnosis of thyroid diseases].

PMID- 7716962
TI  - [Infection as a risk factor in biliary system surgery].
AB  - Infection of the biliary system in which one of the signs is the presence of
      bacteria in bile is connected with an increase of incidence of postoperative
      complications especially in elderly people. Therefore, early diagnosis of
      infections and their prophylaxis and treatment are an important aspect of
      surgical management which is particularly significant in view of large number of
      patients with acute and chronic cholangitis. Proper selection of the operation
      time and the use of antibiotic therapy with adequate utilization of even broader
      spectrum of antibiotics may be of decisive importance for effective treatment.

PMID- 7716963
TI  - [Ovarian function in women after kidney transplantation].
AB  - The full recovery of reproductive age patients suffering from chronic renal
      failure due to a successful transplant should include the restoration of normal
      reproductive functions. In the study data are presented concerning the resumption
      of menstruation and the evaluation of the ovarian function of renal transplant
      recipients. After a successful renal transplant the ovarian function improves
      considerably but isn't always fully restored which can be attributed to the renal
      efficiency grade or result from the administered immunosuppressive treatment.
      Approximately 40% of the patients have ovulatory cycles with a normal length of
      the luteal phase. 40% have also ovulatory cycles but the luteal phase is shorter
      and the progesterone values are lower. The remaining patients have anovulatory
      cycles with low estrogen values and a high FSH and LH concentration.

PMID- 7716964
TI  - [A case of myxoma in the left heart ventricle].
AB  - We report a case of left ventricular myxoma. The diagnosis was established by
      transthoracic 2D--echocardiography. The patient was successfully treated
      surgically.

PMID- 7716965
TI  - [Neurologic symptoms as the first manifestation of Addison-Biermer disease].
AB  - A patient was observed who came with the following symptoms persisting for six
      months: paraesthesia in the lower and upper limbs, weakening of muscle strength,
      difficulties in walking. The high value of the mean cell volume in blood
      morphologic examination called attention to the possibility of vitamin B12
      deficiency which had not yet manifested itself as anaemia. Further studies
      confirmed this suggestion. As the result of the treatment with vitamin B12 full
      normalization of the nervous system condition and results of examinations was
      achieved.

PMID- 7716966
TI  - [A case of thymus tumor lasting over a course of many years].
AB  - A case is presented of a patient with radiological changes in the lungs followed
      up for 12 years. Fine-needle biopsy of the tumour which appeared on the chest
      near the right nipple gave the results: metastatic papillary carcinoma. During
      the autopsy epithelioid thymoma was found infiltrating the mediastinum, right
      lung, intercostal fissure between the 3rd and 4th rib and subcutaneous tissue,
      and also a single metastasis in the liver was detected. Generalized tuberculosis
      was also found with predominance of changes within the abdominal organs.

PMID- 7716967
TI  - [Tuberculosis of the esophagus].
AB  - Tuberculosis of the esophagus is a rare disease, occurring in most cases
      secondary to tuberculous infection of other organs. There are neither
      characteristic symptoms or diagnostic signs, nor typical X-ray or laboratory
      findings. Histology, too, often fails to establish a reliable diagnosis, so that
      esophageal tuberculosis may be mistaken for esophageal carcinoma. Most cases can
      be successfully treated with antituberculous therapy, although patients with
      esophageal tuberculosis in the presence of AIDS do not respond as well to anti
      tuberculous therapy.

PMID- 7716968
TI  - [Laparoscopic cholecystectomy--a meta-analysis of 23,700 cases and status of a
      personal patient sample].
AB  - Meta-analysis of 23,700 laparoscopic cholecystectomies of 27 authors shows an
      intraoperative complication rate of 1.35% and a postoperative complication rate
      of 3%, including injuries of the bile duct in 0.48% and of the intestine in
      0.19%. A second operation was necessary in 1.26%. In 0.43% retained common bile
      duct stones were observed. The conversion rate was 4.1% and the mortality rate
      was 0.08%. Our own experience in laparoscopic cholecystectomy as a standard
      procedure on 455 out of 574 unselected patients (50 acute, 405 elective) resulted
      in 9 (2.2%) intraoperative and 5 (1.2%) postoperative complications. In 4 cases
      (0.9%) the complications necessitated a second operation. The conversion rate was
      11.6% and the mortality rate was zero. It is concluded that the results of
      laparoscopic cholecystectomy appear equivalent the "gold standard" of open
      cholecystectomy up to certain pathomorphological limits. Using an exact
      preoperative diagnostic regimen (sonography, cholangiography, ERCP if indicated)
      the place of routine intraoperative cholaniography is discussed critically.

PMID- 7716969
TI  - [Acute management of para-articular hip fractures in geriatric patients].
AB  - Coxal femoral fractures in the elderly present a growing problem due to the
      increasing life expectancy of the population. The most rapid intervention
      possible with an implant best tailored to the individual's needs and general
      medical condition, followed by early mobilisation and individual
      physiotherapeutic management are the basic prerequisites in the attempt to
      achieve a decrease in the post-operative complication rate, the mortality rate
      and spiraling costs. Preoperative management, the choice of surgical procedure
      according to strict indication criteria and post-operative measures are discussed
      on the basis of an analysis of 719 patients admitted to our department between
      August 1992 and December 1993. The mean age of the patients was 79.9 years and
      the ratio of women to men was 4:1. Operation took place on average 14.2 hours
      after admission and the patients were discharged on average 15.6 days after
      hospitalisation. 37 of 620 (5.9%) patients operated on during the first 24 hours
      (group 1) and 9 of the 99 (9.1%) delayed operation patients (> 24 h = group 2)
      died in hospital. The findings are discussed in the light of the shortage of
      hospital beds, an aging population and rising hospital costs.

PMID- 7716970
TI  - [Congenital abnormalities of the osseous thoracic wall. Results of corrective
      surgery of funnel chest].

PMID- 7716971
TI  - Genetic fatalism and social policy: the implications of behavior genetics
      research.
AB  - Recent advances in molecular genetics methods have provided new means of
      determining the genetic bases of human behavioral traits. The impetus for the use
      of these approaches for specific behaviors depends, in large part, on previous
      familial studies on inheritance of such traits. In the past, a finding of a
      genetic basis for a trait was often accompanied with the idea that that trait is
      unchangeable. We discuss the definition of "genetic trait" and heritability and
      examine the relationship between these concepts and the malleability of traits
      for both molecular and nonmolecular approaches to behavioral genetics. We argue
      that the malleability of traits is as much a social and political question as it
      is a biological one and that whether or not a trait is genetic has little
      relevance to questions concerning determinism, free will, and individual
      responsibility for actions. We conclude by noting that "scientific objectivity"
      should not be used to conceal the social perspectives that underlie proposals
      regarding social change.

PMID- 7716972
TI  - Calcium modulation of the effects of serotonin, carbachol, and histamine on
      rabbit ileal ion transport.
AB  - In mammalian intestine, a number of secretagogues have been shown to work through
      either cyclic nucleotide or calcium mediated pathways to elicit ion secretion.
      Because excessive intestinal electrolyte and fluid secretion is central to the
      pathogenesis of a variety of diarrheal disorders, understanding of these
      processes is essential to the development of future clinical treatments. In the
      current study, the effects of serotonin (5HT), histamine, and carbachol on
      intestinal ion transport were examined in in vitro preparations of rabbit ileum.
      All three agonists induced a rapid and transient increase short-circuit current
      (delta Isc) across ileal mucosa. Inhibition of the delta Isc response of all
      three agents in chloride-free solution or in the presence of bumetanide confirmed
      that chloride is the main electrolyte involved in electrogenic ion secretion.
      Pretreatment of tissue with tetrodotoxin or atropine did not effect secretagogue
      mediated electrolyte secretion. While tachyphylaxis of delta Isc response was
      shown to develop after repeated exposure of a secretagogue to tissue, delta Isc
      responses after sequential addition of different agonists indicate that cross
      tachyphylaxis between agents did not occur. Serotonin, histamine, and carbachol
      have previously been reported to mediate electrolyte secretion through calcium
      dependent pathways. To access the role of extracellular calcium in regulating ion
      secretion, the effect of verapamil on each agent was tested; verapamil decreased
      5HT-induced delta Isc by 65.2% and histamine response by 33.5%, but had no effect
      on carbachol-elicited chloride secretion. An additive secretory effect was found
      upon simultaneous exposure of 5HT and carbachol to the system; no other
      combination of agents produced a significant additive effect. Findings from this
      study support previous work which has suggested that multiple calcium pathways
      may be involved in mediating chloride secretion in mammalian intestine.

PMID- 7716974
TI  - [The physician's responsibility in patient education in HIV infection].

PMID- 7716975
TI  - [Patient education during pregnancy].

PMID- 7716973
TI  - Is alopecia areata an autoimmune-response against melanogenesis-related proteins,
      exposed by abnormal MHC class I expression in the anagen hair bulb?
AB  - The etiology of alopecia areata (AA), a putative autoimmune disease characterized
      by sudden hair loss, has remained obscure. It is not understood, how the
      characteristic inflammatory infiltrate that selectively attacks anagen hair
      follicles in AA is generated. We hypothesize that this reflects an unexplored
      form of autoimmunity, a cytotoxic T cell attack on rhythmically synthesized
      autoantigens normally sequestered by a lack or very low level of MHC class I (MHC
      I)-expression, and suggest the following mechanism of AA pathogenesis:
      Microtrauma, neurogenic inflammation, or microbial antigens cause a localized
      breakdown of MHC I-"negativity" in the proximal anagen hair bulb via
      proinflammatory cytokines. This exposes autoantigens derived from melanogenesis
      related proteins (MRP-DP), which are only generated during anagen, and triggers
      two successive waves of autoimmune responses: CD8+ cytotoxic T cells initiate AA
      after recognizing MRP-DP abnormally presented by MHC I molecules on hair matrix
      melanocytes and/or keratinocytes; a secondary attack, carried by CD4+ T cells and
      antigen presenting cells, is then mounted against MHC class II--presented
      additional autoantigens exposed by damaged melanocytes and keratinocytes. The
      latter causes most of the follicular damage, and extrafollicular disease, and
      depends greatly on the immunogenetic background of affected individuals. This
      unifying hypothesis explains the clinical heterogeneity and all salient features
      of AA, and argues that only the unlikely coincidence of multiple predisposing
      events triggers AA. The suppression of MHC I--expression and synthesis of MRP in
      the hair bulb, and the "tolerization" of MRP-DP autoreactive CD8+ T cells may be
      promising strategies for treating AA.

PMID- 7716976
TI  - [Special problems regarding the physician's responsibility for patient education
      in reproduction medicine].

PMID- 7716977
TI  - [Special problems regarding the physician's responsibility for patient education
      in sterilization of disabled patients].

PMID- 7716978
TI  - [Patient education regarding the suitability of medical practices, hospitals and
      alternative treatment methods--from the legal viewpoint].

PMID- 7716979
TI  - [Patient education regarding the suitability of medical practices, hospitals and
      alternative treatment methods--from the physician's viewpoint].

PMID- 7716980
TI  - [Consent and education in trials of new procedures involving humans--from the
      legal viewpoint].

PMID- 7716981
TI  - [Responsibility for patient education in trials of new procedures in humans from
      the physician's viewpoint].

PMID- 7716982
TI  - [Responsibility for patient education in drug therapy from the viewpoint of the
      drug industry].

PMID- 7716983
TI  - [Responsibility for patient education in drug therapy from the viewpoint of the
      pharmaceutical industry].

PMID- 7716984
TI  - [Responsibility for patient education in drug therapy--from the physician's
      viewpoint].

PMID- 7716985
TI  - [Physician's responsibility for patient education in drug therapy--summary and
      perspectives].

PMID- 7716987
TI  - [Principles and development of the physician's responsibility in patient
      education in the old and new German territories].

PMID- 7716986
TI  - [17th Symposium of lawyers and physicians. Duty to Warn. 4-5 January 1994].

PMID- 7716988
TI  - [Practical problems in the physician's responsibility in patient education from
      the legal viewpoint].

PMID- 7716989
TI  - [Practical problems in the physician's responsibility in patient education from
      the physician's viewpoint].

PMID- 7716990
TI  - [Confidence between patient comprehension and the physician's capacity to educate
      ].

PMID- 7716991
TI  - [Patient education by the physician with incompetence patients or patients with
      limited competence for consent].

PMID- 7716992
TI  - Clinical evaluation of a miniaturized desktop breath hydrogen analyzer.
AB  - A small desktop electrochemical H2 analyzer (EC-60-Hydrogen monitor) was compared
      with a stationary electrochemical H2 monitor (GMI-exhaled Hydrogen monitor).
      RESULTS: The EC-60-H2 monitor shows a high degree of precision for repetitive (n
      = 10) measurements of standard hydrogen mixtures (CV 1-8%). The response time for
      completion of measurement is shorter than that of the GMI-exhaled H2 monitor (37
      sec. vs 53 sec.; p < 0.0001), while reset times are almost identical (54 sec. vs
      51 sec. n.s). In a clinical setting, breath H2-concentrations measured with the
      EC-60-H2 monitor and the GMI-exhaled H2 monitor were in excellent agreement with
      a linear correlation (Y = 1.12X + 1.022, r2 = 0.9617, n = 115). With increasing
      H2-concentrations the EC-60-H2 monitor required larger sample volumes for
      maintaining sufficient precision, and sample volumes greater than 200 ml were
      required with H2-concentrations > 30 ppm. CONCLUSION: For routine
      gastrointestinal function testing, the EC-60-H2 monitor is an satisfactory and
      reliable, easy to use and inexpensive desktop breath hydrogen analyzer, whereas
      in patients with difficulty in cooperating (children, people with severe
      pulmonary insufficiency), special care has to be applied to obtain sufficiently
      large breath samples.

PMID- 7716993
TI  - [Significance of anamnesis and clinical findings for diagnosis of acute
      appendicitis. Acute Abdominal Pain Study Group].
AB  - Acute appendicitis raises considerable diagnostic difficulties. This is proven by
      rates of negative appendectomies that sometimes extent 30%. In order to find
      reasons for this we tested 211 patients findings for diagnostic relevance.
      METHOD: Within the European Community--Acute Abdominal Pain Survey, a study to
      support diagnosis in acute abdominal pain, 1254 patients were seen in the six
      participating German hospitals. 16.8% had appendicitis. History data and physical
      findings were tested for positive and negative predictive value (PPV/NPV),
      sensitivity and specificity (SEN/SPE). RESULTS: We had 15% negative
      appendectomies and 16% perforated appendicies. Only few of the parameters tested
      show a PPW significantly higher than the prior probability of appendicitis:
      (PPV/NPV/SEN/SPE in %) rebound tenderness 39/63/91/80, tenderness in the right
      lower quadrant 36/82/95/70, pain right lower quadrant at presentation
      34/77/94/70, onset of pain right lower quadrant 29/49/88/75, rigidity 28/9/84/95,
      guarding 26/43/87/76. All other parameters had a lower PPV. The combination of
      three parameters leads to maximal PPV of 85%. CONCLUSION: Very few symptoms are
      helpful in diagnosing appendicitis: the pain related symptoms (spontaneous pain,
      tenderness and rebound tenderness, guarding) and the history of the pain hint at
      an appendicitis. A structured and complete medical history and physical
      examination focussing on these few symptoms, a systematic combination of these
      and possibly ultrasonography will improve diagnostic accuracy.

PMID- 7716995
TI  - [A rare cause of upper gastrointestinal hemorrhage: large adenoma of Brunner's
      glands].
AB  - We report the rare case of a large adenoma of Brunner's glands as the cause of an
      upper gastrointestinal hemorrhage. Endoscopic resection is the therapy of choice
      in the appropriate setting. An unequivocal histological diagnosis by forceps
      biopsy often is not possible; there are no clear cut endoscopic criteria. The
      development of complications especially of severe hemorrhage increases with
      diameter of the adenoma. Therefore, the complete excision either endoscopically
      or by surgery should be attempted.

PMID- 7716994
TI  - Essential mixed cryoglobulinemia (EMC) in a case of chronic hepatitis C-
      successful treatment with interferon alpha.
AB  - Chronic hepatitis C virus infection has previously been shown to be associated in
      some cases with an immunologic disorder called "Essential Mixed Cryoglobulinemia"
      (EMC). In this report a case of transfusion-associated chronic hepatitis C will
      be demonstrated. During patient's follow-up over a period of fifteen years the
      woman developed symptoms consistent with the clinical triad of EMC: general
      weakness, polyarthralgias and purpura. Laboratory chemical values support the
      presence of mixed cryoglobulins. Application of different therapeutic strategies
      revealed an improvement of both clinical and biochemical findings during
      interferon-alpha treatment. Results suggest that during chronic hepatitis C virus
      infection interferon-alpha therapy may represent the elective choice of treatment
      for typical symptoms of EMC.

PMID- 7716996
TI  - [Hormone dependence of colorectal carcinomas].
AB  - The question of a possible hormonal control of colorectal cancer growth can be
      examined by several different approaches. At the present time epidemiological
      studies do not give a conclusive answer to this problem. The demonstration of
      functionally active peptide hormone receptors on colon cancer cell lines may play
      a role in a subgroup of receptor-positive tumors only. At the present time a
      classical endocrine mode of action of peptide hormones can be excluded. However,
      there is a possibility of a "hormonal control" of colorectal carcinomas by so
      called "growth factors". In this system the expression of a stimulating growth
      factor, the demonstration of a specific receptor, the blocking of the effect by
      receptor antagonists or growth factor antibodies and the demonstration of a
      functional activity have been fulfilled. The multiple relations between cellular
      protooncogenes and growth factors on the level of the ligand itself, the
      receptors, or the intracellular signal transduction connect the process of
      malignant transformation with hormonal control of growth regulation. This
      connection might offer a basis for a more causal therapy of colon carcinomas
      within the near future.

PMID- 7716997
TI  - [Lymphoma infiltration of the liver: spectrum of ultrasound characteristics in 47
      patients].
AB  - Between 1980 and 1993, 680 patients with malignant lymphoma were referred for
      abdominal sonography as a part of initial staging. In 53 patients intrahepatic
      abnormalities suspected for lymphoma involvement were detected. 6 of these had
      metastases of lung cancer (n = 4) or microabscesses (n = 2). Sonographic findings
      of 47 patients with hepatic lymphoma were reviewed. Hepatic lymphoma was
      confirmed by histologic examination (n = 23) and sonographic/clinical follow-up
      (n = 24). 12 patients had Hodgkin's disease, 18 high-grade NHL, and 17 low-grade
      NHL. Lesions were hypoechoic in all cases. Five different sonographic patterns
      were found: small nodular lesions (n = 28; 60%), large nodular lesions (n = 14;
      30%), bulky disease (n = 2; 4%) and diffuse involvement (n = 2; 4%). One patient
      (2%) had lymphomatous involvement which surrounded the portal vessels. High-grade
      NHL preferred patterns of large nodular or bulky diseases (9 of 17 patients).
      Small lesions were found to be more typical in low-grade NHL (13 of 18 patients),
      and Hodgkin's disease (9 of 12 patients).

PMID- 7716999
TI  - [Hepatocellular carcinoma--transplantation or resection?].

PMID- 7716998
TI  - [Does yearly fecal exam for occult blood lower colorectal cancer mortality?].

PMID- 7717000
TI  - [9th Saxo-Franconian hepatology meeting. Bad Kissingen, 21-22 October 1994.
      Abstracts].

PMID- 7717001
TI  - [Symposium on Uterine Contraction and Beginning of Labor. Aachen, September
      1993].

PMID- 7717002
TI  - [Uterine contraction and labor onset. Overview].
AB  - A survey is given about the general theories of beginning of labour. In this
      topic the influence of excitation of the uterus muscle is explained together with
      the importance of hormonal induction.

PMID- 7717003
TI  - [Control of labor onset in the human].
AB  - While the mechanism of the initiation of labor in humans has not been clarified
      satisfactorily, it is of major clinical interest, particularly with a view to
      understanding and avoiding preterm labor. Progesterone, whose role can now be
      determined in greater detail by the use of newly developed progesterone
      antagonists, and estrogens both play a role. Recently, attention has focused not
      only on contraction-stimulating substances such as oxytocin and prostaglandins,
      but also on cytokines, which have been implicated in the pathogenesis of preterm
      labor related to intrauterine infection. A model describing the various steps
      leading to regular uterine contractions is discussed and the resulting
      implications on stimulation and inhibition by pharmacological substances are
      outlined.

PMID- 7717004
TI  - Role of progesterone during pregnancy: models of parturition and preeclampsia.

PMID- 7717005
TI  - [Prostaglandins and labor onset].
AB  - Prostaglandins and lipoxygenase metabolites of arachidonic acid (Eicosanoids) are
      crucial paracrine regulators of labor. There are many informations about in vitro
      production and the physiological or pathophysiological role and clinical
      importance of these substances. However, the all decisive mechanism of the
      involvement of eicosanoids in birth process is still unknown. In this review we
      describe the present knowledge about endocrine, paracrine and autocrine
      regulations of uterine contractions.

PMID- 7717006
TI  - [Biochemical principles of cervix ripening and dilatation].
AB  - The central function of the cervix to maintain pregnancy is biochemically
      characterized by an increased synthesis of collagen, proteins, glycosaminoglycans
      (GAG) and fibronectin within the extracellular matrix, thus leading to an
      increase of cervical volume without significant changes of cervical consistency.
      During the time of cervical ripening we found a marked reduction of collagen
      concentration, a 2.5-fold increase in GAG content, a significant fall in dermatan
      sulfate concentrations from 41% to 15% of total GAG content, a 12-fold increase
      in hyaluronate concentrations, and a marked reduction in fibronectin,
      demonstrated by immunhistochemical methods. Thus, the loss of collagen and
      sulfated GAGs may facilitate distensibility in the ripened cervix, while the
      significant gain in hyaluronate associated with hydratation may explain the soft
      and swollen consistency. In this connection increased hyaluronate concentrations
      and degradation of fibronectin may play a trigger role for subsequent cervical
      dilatation. The dramatic changes of the cervix during parturition occurring
      within a few hours require the rapid activation and action of catabolic enzyme
      systems. Our studies showed a significant increase of sialidase-, collagenase-
      and elastase activities during cervical dilatation. These proteinases originate
      from polymorphonuclear leucocytes (pml), which accumulate in cervical capillaries
      at the onset of labor; this is followed by a massive leucocyte infiltration of
      the cervical stroma at the beginning of cervical dilatation and a degranulation
      of the pml at further dilatation, thus releasing collagenase and other
      proteinases. This process is limited by the immediate post partum insudation of
      the cervix by plasma containing highly potent proteinase inhibitors. The clinical
      aim of our basic biochemical studies is to develop new concepts in the causal
      treatment of cervical pathology during pregnancy.

PMID- 7717007
TI  - [Role of the cervix uteri at labor onset from ultrasound studies].
AB  - The cervix uteri is of greatest importance for the environment of the fetus. The
      sonographic imaging of the cervix uteri can be done by transabdominal, perineal
      and transvaginal route. Each of these methods are associated with specific
      advantages and disadvantages. During the time of gestation the cervix uteri can
      be measured sonographically concerning the length, the thickness, the width of
      the cervical canal and in addition the diameter of the internal and the external
      os. At the beginning of labour the cervix shows a transformation: a shortening
      with an increase of thickness. The phase of contraction is followed by a phase of
      reformation. Individual formations of the cervix regarding the a premature
      opening of the internal os or the external os could be demonstrable without
      clinical symptoms. By W. Eppel a score-like formula "Incompetence-Factor" was
      described for a quantification of these measurements.

PMID- 7717008
TI  - [Adrenergic beta-2 receptors and cyclic AMP in lymphocytes and their relationship
      to uterine contractility].
AB  - It is especially in the long-term application where the pharmacodynamics of the
      betamimetics determine their effectiveness. According to the time and dosis,
      there is a decrease in the density and function of the beta 2-adrenoceptors
      (desensitization). Clinically, this means a loss of effectiveness. This study
      investigated whether in the course of a normal pregnancy (n = 22) there is a
      change in the effectiveness of the betamimetics, as expressed by a change in the
      number of beta 2-adrenoceptors or their function. The results show a 50% decrease
      in the number of beta 2-adrenoceptors to the 36th gestational week and an
      increase to initial values after delivery. A similar pattern is found for the
      function of the beta 2-adrenoceptors (cyclic AMP). The implications for the
      uterus might be that, with advancing pregnancy, it becomes less prone to
      relaxation and that the betaadrenergic system, as a mechanism supporting prepare
      the way for delivery at term, becomes less significant. For tocolysis with
      betamimetics, the decrease of the beta 2-adrenoceptor density means that, with
      increasing gestational age, the responsiveness of the uterus to betamimetics
      decreases.

PMID- 7717009
TI  - [Significance of the site of uterine contraction for labor progress and duration
      of pregnancy].
AB  - A four-channel topographic technique was developed in order to improve
      information about spatial uterine motility. 54 women were monitored during
      delivery. Four pressure transducers were attached in a square around the
      umbilicus. Most frequently the origin of labour could be determined in the upper
      right segment of the uterus. The rate of operative deliveries was decreased in
      case of predominant upper right origin of labour. The majority of contractions
      with clear propagation patterns originated at the upper right site, continued to
      the left and then to the lower right part of the uterus. The highest relative
      intensity was also measured at the upper right site. Predominant upper right
      origin of labour may be important for undisturbed delivery. The probability of a
      preterm delivery is increased in case of an upper right origin of labour.

PMID- 7717010
TI  - [Prolonged pregnancy--prostaglandins as the cause of labor onset].
AB  - The causes of prolonged pregnancy are still largely unknown and their
      investigation requires a detailed observation of potential birth-initiating
      stimuli on the endocrine and biomolecular level. A large number of clinical and
      biochemical studies point to the central importance of prostaglandins for the
      beginning of human birth. The main places of origin of the intensified
      prostaglandin formation and release are the amnion and the decidua which has
      "macrophage-like" properties and functions. The superordinate regulation and
      trigger mechanisms for intensified uterine prostaglandin production has not been
      sufficiently investigated either. Possible factors currently being debated
      include local changes in estrogen and progesterone biosynthesis in fetal
      membranes and decidua, subclinical inflammatory reactions with the activation of
      macrophages and the consecutive release of cytokines, and a loss of maternal
      immune tolerance with a time-determined rejection reaction. In addition, the
      substances inhibiting and stimulating prostaglandin synthesis have been detected
      in the amniotic fluid, fetal membranes and decidua. The fetus itself also plays
      an important part in the initiation of labor. Prolongation may be due to anatomic
      functional disturbances of the one hand which prevent the activation of the fetal
      hypothalamic-hypophyseal-adrenal axis and the release of the birth-initiating
      stimuli originating in the fetus; on the other hand, an elevated immune tolerance
      with a delayed rejection reaction or the lack of "bacterial stimulus" may inhibit
      the activation of the macrophages and hence the formation of cytokines. The
      consequences would be the development and release of a quantity of prostaglandins
      from the fetal membranes and decidua insufficient to overcome the pregnancy
      maintaining safety systems.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717011
TI  - [Infection and uterine contraction].
AB  - A great number of studies on women as well as experiments on animals support the
      association of silent intrauterine infection with the initiation of preterm
      labour. However, the success of antibiotic therapy in reducing bacteria-induced
      labour in animals could only be confirmed in few reports concerning women in
      preterm labour. Disregarding direct effects of bacterial products such as
      Phospholipase-A2 and endotoxins evidence suggests that immunological effects
      (release of Cytokines) may enhance the synthesis of prostaglandins in the uterus,
      placenta and fetal membranes. New therapeutical approaches are in discussion, but
      only time will tell whether a reduced rate of women with failed tocolysis will be
      the result.

PMID- 7717012
TI  - [German Society for Cardiology, Heart and Circulation Research. List of members,
      1993/94].

PMID- 7717013
TI  - [Increased vagal activity after administration of the calcium antagonist
      diltiazem in patients with coronary heart disease].
AB  - The effects of the calcium channel blockers diltiazem on the parasympathetic
      nervous system were studied by using spectral analysis of heart rate variability,
      and were compared with the effects of the beta-receptor blocker metoprolol. The
      area under the curve of the high-frequency range (f = 0.18-0.35 Hz) during
      controlled respiratory rate (f = 0.25 Hz) was used as a quantitative index of
      parasympathetic activity. Twenty-four male patients with proven coronary artery
      disease and normal left ventricular function (LVEF > 60%) were studied 2 weeks
      after chronic treatment with diltiazem (3 x 60 mg daily) or metoprolol (3 x 50 mg
      daily) before and after administration of the drug. Twelve patients received
      diltiazem and 12 patients metoprolol. After administration of diltiazem the
      peripheral systolic blood pressure was reduced, but the parasympathetic activity
      was significantly higher than compared with the initial measurement. The same
      effect was seen for metoprolol, but a significant lower heart rate was present
      after administration. The relative area under the high-frequency range
      significantly increased at rest, by 110% after diltiazem and 70% after
      metoprolol. Diltiazem and metoprolol enhance the vagal influence at the heart,
      thereby leading to an enhancement of barosensitivity and of the respiratory sinus
      arrhythmia. This action may contribute to the beneficial effects of both drugs in
      patients with coronary artery disease.

PMID- 7717014
TI  - [Coronary reserve after orthotopic heart transplantation: quantification with N
      13 ammonia and positron emission tomography].
AB  - Coronary transplant vasculopathy is known to be associated with an early
      impairment of endothelium-dependent vasodilatation. In this study the largely
      endothelium-independent dilator response to dipyridamole was evaluated in 22
      patients 36 +/- 17 months after transplantation in relation to their angiographic
      findings. The dipyridamole coronary reserve was measured by N-13 ammonia and
      positron emission tomography (PET). Transplant vasculopathy was suspected or
      evident in 13 of 22 patients by coronary angiography. Coronary reserve was lower
      in transplant recipients than in normal controls (2.3 +/- 0.9 vs. 4.7 +/- 1.4).
      Those with a normal angiogram had a near normal minimal coronary resistance (0.3
      +/- 0.04 mmHg.min.100 g/ml) and a normalized coronary reserve after correction
      for the increased resting blood flow (4.8 +/- 0.7). However, in patients with
      angiographic vasculopathy, coronary reserve was markedly reduced (1.8 +/- 0.7,
      corrected 2.7 +/- 1.0) and minimal coronary resistance was elevated (0.6 +/- 0.3,
      p < 0.001). Moreover, regional coronary reserve was homogeneously reduced
      throughout the myocardium without a clear segmental relationship to angiographic
      stenoses. After testing of other factors known to influence coronary resistance,
      our data are compatible with diffuse obstructions of the microvascular bed that
      are associated with an angiographically visible vasculopathy. The evaluation of
      coronary reserve by dipyridamole and PET provides a useful extension of
      angiography in these patients.

PMID- 7717015
TI  - [Variability of transplant vasculopathy. A study with intravascular ultrasound].
AB  - Cardiac allograft vasculopathy (CAV) influences long-term survival of patients
      after heart transplantation. Histopathology studies have demonstrated the
      insensitivity of coronary angiography (CA) for detecting CAV. Intravascular
      ultrasound (IVUS) is an imaging technique that provides qualitative and
      quantitative characterization of vessel wall morphology. The purpose of this
      study was to compare in vivo IVUS with coronary angiography in cardiac transplant
      recipients and to analyze intraindividual and segmental variability of CAV
      involvement. IVUS studies were performed at routine follow-up angiography in 33
      patients 48 +/- 23 months after heart transplantation. 134 segments (1 to 8 per
      patient) were classified by IVUS according to a modified Stanford score
      (morphometric grading from 1 to 6). Patient characteristics and laboratory
      findings were further compared with intimal thickening. 114/134 (85%) segments
      were normal with CA. In 56% of these segments, IVUS revealed mild to moderate
      (IVUS grade 2 to 4, n = 45) or severe (IVUS grade 5 to 6, n = 19) intimal
      thickening. Mean IVUS scores between proximal and distal segments were not
      different (2.9 +/- 1.9 vs. 2.4 +/- 1.9, ns). Intimal thickening was more
      pronounced in segments of the LAD compared to the RCX (3.1 +/- 2.0 vs. 2.03 +/-
      1.6, p < 0.01). In 39% of patients, the intraindividual extent of CAV was very
      heterogeneous (range: 3 to 5 IVUS grades). There was no significant correlation
      between IVUS and clinical or laboratory findings. IVUS is a sensitive method for
      the in vivo detection of CAV, while even severe intimal thickening can often not
      be identified by CA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717016
TI  - [Therapy of hypercholesterolemia after heart transplantation with the HMG-CoA
      reductase inhibitor simvastatin in long-term follow-up].
AB  - The problem of hypercholesterolemia following heart transplantation (HTx) is
      often underestimated. Up to now there is no concept of therapy allowing an
      optimal adjustment of lipid parameters. Therapeutical trials using ion exchange
      resins, derivates of nicotinic acids and fibrates were not successful due to
      Cyclosporin A interaction, hepatotoxicity and limited efficacy of the applied
      substances. In a prospective, randomized and controlled trial, we investigated
      the effects of monotherapy with the HMG-CoA-reductase inhibitor Simvastatin in
      heart transplant recipients. The study included 70 patients (Simvastatin n = 37,
      control group n = 33). Eight patients died within the first 3 month
      postoperatively following HTx. Purpose of the study was adjustment of LDL
      cholesterol-values in the Simvastatin-treated group to < 110 mg/dl. Following 24
      months of treatment a mean LDL-cholesterol-plasma level of 110 mg/dl was
      obtained. The corresponding mean value of the control group was 150 mg/dl. The
      difference between both groups was significant (p < .001). In the same period the
      mean HDL-cholesterol values increased by approximately 15% in both groups. The
      ratio of LDL-/HDL-cholesterol was significantly lower in the Simvastatin treated
      group (2.28) than in the control group (2.94) (p < .01). There was no significant
      difference in Lp(a)-values. No adverse effects were observed within the following
      period of 24 months, particularly no increase in the frequency of rejection
      episodes. The drug induced hypercholesterolemia following HTx could be treated
      safely and effectively by low-dose Simvastatin.

PMID- 7717017
TI  - [Neurocardiac syncope: pathophysiology, diagnosis, therapy].
AB  - The diagnostic work-up and the appropriate therapy of patients with recurrent
      syncopy represents an often encountered clinical problem. The underlying etiology
      of a syncopal episode remains not infrequently unknown despite intensive and
      sometimes costly diagnostic procedures. Particularly in young patients with
      syncopal attacks, the diagnosis of neurocardiogenic syncope has been established
      on the basis of normal findings during conventional cardiologic and neurologic
      work-up. Only since the introduction of the tilt-table test into clinical
      practice has the clinician had a diagnostic tool to prove the neurocardiogenic
      etiology of a syncopal episode. It has been demonstrated that this diagnostic
      method yields a good reproducibility which makes it suitable to assess the
      efficacy of therapeutic interventions. There have been several therapeutic
      recommendations according to the multifactorial pathogenesis of neurocardiogenic
      syncope. Among these, therapy with beta-receptor blocking agents or with
      theophylline appears to be the most promising treatment modalities. The results
      obtained in the studies reviewed in the present article have increased our
      knowledge with respect to the pathogenesis of neurocardiogenic syncope as well as
      the diagnostic procedures and treatment modalities in patients afflicted with
      this disorder.

PMID- 7717018
TI  - [Noninvasive diagnosis of coronary heart disease with cardiokymography: use of
      signal averaging technique].
AB  - Regional wall motion abnormality is the best indicator for coronary ischemia.
      Myocardial wall motion is registrated by cardiokymography (CKG), a
      mechanocardiographic method. Because of the high incidence of artefacts,
      echocardiography and nuclear imaging technique have been preferred. Computer
      assisted signal averaging CKG improves practicability and allows measurements
      during exercise testing. Exercise testing was performed in 54 patients with
      suspected ischemic heart disease without mitral or aortic valve dysfunction,
      myocardial infarction or prior cardiac surgery. The results of simultaneously
      recorded ECG and CKG were compared with coronary angiographic results. CKG
      sensitivity and specificity were higher than that of ECG (76 and 80% vs 71 and
      52%). If diagnosis was based on pathological or nonpathological results of both
      CKG and ECG, sensitivity and negative predictive value increased to 87 and 83%,
      respectively. Sensitivity reached 93% when only one pathological result was
      required. CKG combined with signal-averaging techniques has advanced to become a
      specific and sensitive tool in the non-invasive diagnostic approach to ischemic
      heart disease.

PMID- 7717019
TI  - [Quantitative light and electron microscopy studies of myofibrils and
      mitochondria of dog and chicken hearts].
AB  - Ventricular myocytes are characterized by a central nucleus which is surrounded
      by longitudinal myofibrils and a mostly column-like longitudinal distribution of
      mitochondria. This study was designed to investigate the subcellular distribution
      of organelles in close proximity to the nucleus. Of particular interest was the
      question of whether volume density of organelles close to the nucleus is
      maintained and, as a consequence, if the cellular diameter at the site of the
      nucleus is increased according to the dimension of the nucleus. Therefore, dog
      and chicken hearts were subjected to perfusion fixation and sections of myocytes
      were studied in longitudinal and cross-sectional axes by light and electron
      microscopy. Volume density of organelles was analyzed on longitudinal sections
      according to Rosiwal's principle and on cross-sections by the point-counting
      method and a digitalized imaging system. We found that the cross-sectional
      diameter of cardiac myocytes is slightly wider at the site of the nucleus
      according to the dimension of the nucleus. The volume density of myofibrils and
      mitochondria is similar in most subcellular fractions except at the nuclear poles
      where mitochondria were significantly more abundant. Thus, no significant
      disturbance of the organelle distribution is observed at the site of the nucleus.

PMID- 7717020
TI  - [Right ventricular metastasis of renal cell carcinoma 10 years after kidney
      transplantation].
AB  - In a 61-year-old man, renal cell carcinoma of the right kidney was diagnosed 10
      years after renal transplantation. Echocardiography revealed a right ventricular
      mass 5.5 x 3.5 m in size. The patient died suddenly 10 weeks later, post-mortem
      examination confirmed diagnosis of right ventricular metastasis of renal cell
      carcinoma. This case underlines the importance of echocardiographic examination
      in tumor patients if signs of heart failure, angina pectoris, embolism, or rhythm
      disturbances arise; or if cardiac murmur becomes audible, or heart size
      increases.

PMID- 7717021
TI  - [Change in the patient profile in coronary heart disease at the time of initial
      evaluation with coronary angiography between 1975 and 1989].
AB  - BACKGROUND AND METHOD: After the introduction of coronary angioplasty in the late
      1970s, diagnostic coronary angiography has been performed for reasons other than
      to evaluate patients for bypass surgery. The aim of this study was to evaluate
      the change of the patient-profile at the time of the first angiographic
      evaluation of coronary artery disease. Therefore, 6456 patients in the period
      from 1975 to 1989 were included. RESULTS: The observation period of 15 years was
      divided into three parts of 5 years each (group 1 1975-79, N = 1130); group 2
      1980-84, N = 2412; and group 3 1984-89, N = 2914). The mean age (53.3 +/- 7.4 vs.
      54.4 +/- 8.4 vs. 57.8 +/- 9.3; p < 0,0001) as well as the number of patients of
      age > 64 years (6.4% vs. 9.6% vs. 25.9%, p < 0.0001) increased significantly over
      the 15 years. Women were found twice as often in group 3 vs. group 1 (10% vs. 16%
      vs. 19%; p < 0.0001). In the observation period the left ventricular ejection
      fraction (51.1 +/- 15.9 vs. 53.8 +/- 14.4 vs. 55.4 +/- 16.2) and one-vessel
      disease (37.2% vs. 38.2% vs. 42.4%) increased significantly (p < 0.0001), whereas
      multi-vessel disease decreased (57.7% vs. 56.6% vs. 52.6%). CONCLUSION: Between
      1975 and 1989 significantly more women, more patients over 64 years of age, and
      more patients with lower degree of coronary disease were first evaluated with
      coronary angiography. The change of patient-profile may have been influenced by
      increased risk-factors among women and the possibility to offer patients an
      alternative therapy to bypass surgery.

PMID- 7717022
TI  - [Association of lipoprotein (a) with the extent of coronary atherosclerosis in
      surgically revascularized men and women].
AB  - Lipoprotein (a) (Lp(a)) levels are genetically determined and levels higher than
      25 mg/dl are associated with increased prevalence of coronary artery disease
      (CAD). We studied gender differences in 76 men and 20 women undergoing coronary
      artery bypass graft surgery (CABG) for a potential association between Lp(a)
      levels both in serum and the aortic wall (Apo(a)) and the severity of CAD
      determined by an atherosclerosis score (CS) using quantitative coronary
      angiography (QCA). Serum Lp(a) and tissue Apo(a) do not correlate with the
      severity of CAD as assessed from QCA (r = 0.09 and r = 0.14, resp.). 60% of women
      but only 39% of men had serum Lp(a) levels higher than 25 mg/dl. Women were 8
      years older (65 +/- 8 vs. 57 +/- 8 years, p < 0.001) and had 1.5 times higher
      mean serum Lp(a) and 1.75 times higher mean tissue Apo(a) levels (47 +/- 41 vs.
      32 +/- 40 mg/dl and 33 +/- 34 vs. 19 +/- 24 micrograms/g WW, p < 0.05) than men
      with identical CS (35 +/- 8 vs. 33 +/- 8, p = NS). The serum levels of
      cholesterol, triglycerides, and high-density lipoprotein were similar in the two
      groups. There is no association between Lp(a) and Apo(a) and the severity of
      coronary atherosclerosis in men and women undergoing coronary artery bypass
      surgery.

PMID- 7717023
TI  - [Fibrinogen and leukocyte number in coronary heart disease. Correlation with
      angiography and clinical degree].
AB  - In 302 consecutively patients fibrinogen (Clauss method) and leucocyte count were
      related to the angiographic and clinical degree of coronary atherosclerosis.
      Fibrinogen (mg/dl) was statistically higher compared to control (C, 267 +/- 55)
      in patients with one-vessel disease (1-vd (306 +/- 67), 2-vd (331 +/- 73), and 3
      vd (328 +/- 62)). Patients with coronary sclerosis (Scl, luminal irregularities
      and/or stenosis under 50%) showed a tendency to higher fibrinogen levels (291 +/-
      58) as compared to controls. Leucocyte count (10(9)/L) compared to C (6.7 +/-
      1.8) was significantly higher in 1-vd (7.6 +/- 2.0) and 2-vd (7.6 +/- 1.9). A
      subgroup analysis was performed with 100 patients having severe forms of angina
      pectoris (AP III according to the CCS classification, unstable angina). Hundred
      sixteen patients with unstable angina (390 +/- 79), particularly with angina at
      rest during the last 48 h were characterized by the highest fibrinogen values
      (423 +/- 89, class III B/C Braunwald). Leucocyte count in patients with stable
      angina (7.2 +/- 1.4) and angina at rest (9.3 +/- 2.7) was significantly higher as
      compared to control (6.7 +/- 1.8). Hyperfibrinogenemia and relative leucocytosis
      correlate with the angiographic and clinical extent of coronary artery disease
      and may offer evidence of a higher degree of thrombogenesis associated with
      components of inflammation.

PMID- 7717024
TI  - [Gender bias in diagnosis and treatment of women with coronary heart disease. A
      review].
AB  - Recent studies collected via Medline and Psychlit suggest that coronary heart
      disease is treated less aggressively in women than in men. Women have
      significantly less access to major diagnostic and therapeutic procedures such as
      thrombolytic therapy, coronary angiography, coronary angioplasty, and coronary
      artery bypass surgery. This holds for women with suspected coronary heart disease
      as well as for women with coronary heart disease documented by myocardial
      infarction or coronary angiography. Possible reasons for gender bias in the
      management of coronary heart disease are: 1) physicians may underestimate the
      prevalence of coronary heart disease in women, 2) because of the higher
      prevalence in men, physicians may consider coronary heart disease as more serious
      in men, 3) a general lack of knowledge concerning coronary heart disease in
      women, 4) physicians' perceptions of gender-specific differences in risks and
      benefits of certain procedures, 5) gender stereotypes of the physician, 6)
      presentation style of the patient.

PMID- 7717025
TI  - Single lung transplantation in the rabbit: an alternative proposal for the study
      of preservation devices.
AB  - The authors report their standard protocol for single lung transplant in New
      Zealand rabbit, the anaesthesiological approach consisted of a premedication with
      Ketamine 35 mg/kg i.m., Atropine sulphate 0.25 mg/kg s.c. and Fentanil 0.1
      mg/i.m.; a jugular vein was cannulated and the anaesthesia was carried out
      administering Ketamine 10-15 mg/kg every 20 min., plus Fentanil 0.1 mg every 30
      min. The rabbit was intubated through a tracheostomy, curarized and room air was
      administered using an appropriate ventilator device. The heart-lung en bloc
      removal from the donor was performed through a midline sternotomy. The left lung
      was then separated leaving an adequate cuff of left atrium inclusive of right
      pulmonary veins which were ligated using a 7-0 thread the graft prepared in this
      way was then preserved by putting it into the perfusion solutions. The recipient
      rabbit, after anaesthesia, underwent left pneumonectomy through a left toracotomy
      the bronchial anastomoses was first performed, followed respectively by the
      arterial and the atrial sutures. The controlateral pulmonary artery was then
      clamped and sequential arterial samples were taken from descending aorta
      previously cannulated to obtain arterial gases tests. The recipient rabbit has
      been followed up this way no more than 2 hour time, than it was sacrificed.

PMID- 7717026
TI  - Autoperfused heart-lung preparation: one reason for unsuccessful lung
      preservation.
AB  - Normothermic autoperfused heart-lung preparation has the advantages of avoiding
      ischemic time and allowing continuous monitoring of organ function during
      preservation. When this technique is used, the lungs deteriorate quickly, but the
      reasons for this deterioration have not been investigated. This study was
      designed to explore the possible cause of rapid lung deterioration. Three groups
      of mongrel dogs were used. In Group 1 (N = 5), a buffer bag was used in the heart
      lung preparation. In Group 2 (N = 6), a 20 mu filter was incorporated between the
      buffer bag and the right atrium. In Group 3 (N = 5), no buffer bag was used.
      Average survival time was 15.0 +/- 3.1 hours in Group 1, 13.5 +/- 0.7 hours in
      Group 2, and 21.6 +/- 2.3 hours in Group 3. Heart function was comparable among
      the three groups, but the arterial pulse pressure was lower and the heart rate
      higher in Group 3. Both white blood cell and platelet counts decreased
      contonuously during the preservation period. Examination of the filters in Group
      2 revealed numerous aggregates consisting of platelets, white blood cells, red
      blood cells, and fibrin. Small thrombi were also found in the lungs in Groups 1
      and 2. The results indicated that one important reason for quick lung
      deterioration was numerous aggregates, which were formed in the buffer bag,
      returned from the venous line, and trapped in the lungs. Removal of the buffer
      bag reduced the production of aggregates but tended to de-stabilize the
      hemodynamics of the preparation.

PMID- 7717027
TI  - Experimental study of lung transplantation from non-heart-beating donor following
      brain death in canine model of left lung allotransplantation.
AB  - Thirty mongrel dogs were divided into 3 groups. Group I was a normal control
      group (n = 4) without transplantation procedure. Group II was a transplantation
      control group (n = 5) with left lung allotransplantation from heart-beating
      donor. Group III consisted of animals (n = 8) which received lung allografts from
      non-heart-beating donor following brain death. In Group III, brain death was
      brought about by intracranial hypertension with the inflation of balloon in the
      subdural space of donor. After 6 hours, the mechanical ventilation was
      discontinued followed by cardiac arrest. Left lung was excised twenty minutes
      after the cardiac arrest and was washed out with cold Ep4 solution for subsequent
      orthotopic allotransplantation. Right pulmonary arterial occlusion test (RPAO)
      were carried out under right thoracotomy to evaluate graft function immediately
      and 7 to 14 days after the surgery. PaO2, PAP and CO were measured before and 20
      minutes after RPAO. All animals in Group II and 7 of 8 animals in Group III
      survived more than 7 days after surgery. No significant differences in the value
      of PaO2, mean PAP and TPVR with RPAO among three groups at each time of
      assessment, showing the possibility of lung transplantation from non-heart
      beating donor followed by brain death.

PMID- 7717028
TI  - Haemmaccel, a key for lung preservation?
AB  - Several and different solutions have been used for lung preservation but, at
      present, fluids and solutions are quite alike. In the last years extracellular
      type solutions have been progressively tested in experimental researches and have
      shown a better protection vs intracellular one. In this research we have studied
      the effect of a low-potassium solution normally used as plasma expander
      (Haemmaccel, HM) on isolated foetal human fibroblasts (WI-38). HM has been
      compared with Belzer solution (UWS) after 16 hrs incubation at 10 degrees C and
      low-potassium solutions with dextran 2% and 5% after 6 hrs and 16 hrs incubation
      at 10 degrees C. Wi-38 cells have been seeded at the density of 9x10(4)/cm2 onto
      plastic well plates. Cellular viability was measuring using the rate of protein
      synthesis through the incorporation of 3H leucine in growth medium during a 1 hr
      incubation at 37 degrees C. The results were expressed as nmol 3 H leu/mg of
      proteins/minute and presented as means +/- SD; the comparison has been performed
      by the one way variance analysis test. After 16 hrs incubation at 10 degrees C HM
      preserves WI-38 cells significantly better than UWS. Comparing HM with LPD 2% and
      5% a significant difference both at 6 hrs and at 16 hrs was observed. Our
      preliminary in vitro results confirm that low-potassium solutions are less toxic
      on isolated lung cells than intracellular one. Polygelin contained in HM could be
      considered a suitable colloidal substance that determine a better preservation if
      compared with Low-Potassium Dextran solutions.

PMID- 7717029
TI  - Efficacy of a rinse solution for the prevention of reperfusion injury in canine
      preserved lungs.
AB  - To evaluate the efficacy of a perflurocarbon emulsion (Fluosol: FC-43) for
      protecting preserved lungs from ischemic reperfusion injuries, we employed an
      isolated canine left lung reperfusion model. The left lung from 15 mongrel dogs
      was flushed and preserved in Euro-Collins solution for 24 hrs at 4 degrees C. The
      preserved lungs were rinsed through the pulmonary artery with a perflurocarbon
      emulsion (perfluorotributylamine: FC-43) or Carolina rinse solution II (CRS-II)
      and then reperfused with whole blood for 120 minutes. The lungs were divided into
      three groups; lungs reperfused without rinse (Group 1: n = 5), and lungs rinsed
      with oxygenated FC-43 (Group 2: n = 6) or CRS-II (Group 3: n = 4). Reperfusion
      was with whole blood warmed to 37 degrees C. The pulmonary vascular resistance
      was lower in the lungs in Group 1 than in those in Groups 2 and 3 (84.2 +/- 33.3
      v.s. 322.3 +/- 190.5 and 474.1 +/- 219.0 mmHg/L/min, p < 0.01). There was no
      significant difference in the PaO2 among the 3 groups at the end of reperfusion.
      The extravascular lung water (dry/wet ratio) was lower in the lungs in Group 2
      than Groups 1 and 3 (90.5 +/- 0.7% v.s. 86.8 +/- 2.1% and 92.1 +/- 2.1% p <
      0.01). These data demonstrated that pulmonary function and structure were
      maintained well in lungs reperfused with FC-43. We conclude that a
      perfluorocarbon emulsion (FC-43) is useful for protecting ischemic canine lungs
      from reperfusion injury, but Carolina rinse solution II is not effective for
      minimizing reperfusion injury in canine lungs.

PMID- 7717030
TI  - Two-day preservation of the lungs by normothermic perfusion.
AB  - Lung function was studies during a 2-day preservation period. The lungs were
      removed along with the heart, liver, pancreas, duodenum, and both kidneys while
      they were still perfused by the heart and oxygenated by the lungs. In 12
      experiments the organs survived an average of 49.2 hours. Arterial blood
      pressures were maintained at 74-95 mmHg, and no inotropic drugs were used. When a
      gas mixture of 50% O2 + 3% CO2 + 47% N2 was used, arterial oxygen tension ranged
      from 239 +/- 23 to 305 +/- 16 mmHg; carbon dioxide tension ranged from 17.6 +/-
      1.8 to 24.9 +/- 2.9 mmHg; and pH ranged from 7.31 +/- 0.03 to 7.49 +/- 0.04.
      Maximum airway pressure ranged from 12.5 +/- 1.7 to 28.0 +/- 2.2 mmHg. Airway
      resistance ranged from 0.020 +/- 0.006 to 0.049 +/- 0.007 mmHg/ml and increased
      after 40 hours. Lung tissue wet/dry weight ratio was stable during the
      preservation period. The results showed that the lungs were well preserved in the
      normothermic perfusion preparation for up to two days with minimal functional
      changes.

PMID- 7717031
TI  - Heart-lung protection from ischemic injury during 8 hour hypothermic
      preservation.
AB  - Optimal techniques of heart-lung preservation are yet to be defined. The aim of
      this study was to develop, in a canine model, a method of heart-lung preservation
      which would permit distant procurement of the organs. The animals were divided
      into 2 groups. In the experimental group (N = 6) the method of preservation
      consisted of cold cardioplegic arrest of the heart with St. Thomas' Hospital
      solution containing superoxide dismutase, catalase and deferoxamine, followed by
      cold pulmonary artery flush with modified Euro-Collins solution to which
      prostaglandin E1, superoxide dismutase, catalase, deferoxamine and Dextran 40
      were added. Following harvesting, the heart-lung block was stored for 8 hours in
      cold (4 degrees C) Euro-Collins solution containing superoxide dismutase,
      catalase, deferoxamine, lactobionic acid, raffinose, mannitol, Dextran 40,
      magnesium sulfate, insulin and penicillin. In the control group (n = 6), the
      heart-lung block underwent the same treatment as the experimental group except
      that lactobionic acid, raffinose and insulin were omitted from the storage
      solution, and that oxygen radical scavengers were excluded from the cardioplegic,
      pneumoplegic and storage solutions. Histologic and electron microscopic
      examinations of heart-lung specimens taken before and after 8 hours cold storage
      of the organs suggested that our preservation technique may be effective in
      preventing ischemia-induced injury.

PMID- 7717032
TI  - Effect of glutathione on hypothermic lung preservation.
AB  - Three groups of rats were used to test the effect of glutathione in hypothermic
      lung preservation. In the Normal Group (N = 8), lung function was studied
      immediately after removal without preservation. In the Euro-Collins (EC) Group (N
      = 8), the lungs were flushed with cooled Euro-Collins solution and preserved in
      EC solution for 24 hours. In the glutathione (GSH) Group (N = 8), glutathione (3
      mM/L) was added to cooled Euro-Collins solution for perfusion and preservation.
      Lung function studies were performed by using living donor rats for perfusion.
      Venous blood from the host rat perfused the isolated lung, and the blood returned
      from the lung was pumped back into the internal carotid artery of the host rat.
      Oxygen tension in the returned blood (PvO2) in the Normal Group was higher than
      that in either the EC Group or the GSH Group. Pulmonary vascular resistance and
      airway resistance were much lower in the Normal Group than in the EC Group and
      GSH Group. Lung tissue wet/dry weight ratio after perfusion was 6.25 in the
      Normal Group, which was lower than that in the GSH Group (8.69, p < 0.05) and
      much lower than that in the EC Group (6.82, p < 0.05). Severe pulmonary edema and
      hemorrhage occurred after 30 minutes of perfusion in the EC Group, whereas a 60
      minute perfusion was performed in the Normal and GSH Groups. The results
      indicated that rat lungs were better preserved with glutathione, but the effect
      was not dramatic.

PMID- 7717033
TI  - Evaluation of a cardiopulmonary preservation method for heart-lung
      transplantation.
AB  - This study was designed to examine whether concomitant administration of anti
      free radicals with donorcore cooling on cardiopulmonary bypass (CPB) and
      hypothermic storage of the heart and lung, could provide successful extended
      cardiopulmonary preservation. Fourteen sheep heart-lung blocks harvested after
      core-cooling and cardioplegic arrest were preserved at 4 degrees C for 8.5 hr.
      Before and during CPB, the animals were perfused with Prostaglandin E1 (PGE1),
      superoxide dismutase (SOD), catalase (CAT) and deferoxamine (DEF). Cardioplegic
      arrest was induced with St. Thomas' Hospital solution (Plegisol) to which SOD,
      CAT and DEF had been added. The preservation solution consisted of Plegisol
      modified by the addition of K-lactobionate, raffinose, mannitol, SOD, CAT, DEF, a
      phosphate buffer and penicillin. Histological examination performed on 3 donor
      heart-lung blocks before and after CPB and cardioplegia, then immediately
      following cold storage, produced no clear evidence of structural damage in
      cardiac myocytes and lung parenchyma. Eleven donor organs were therefore
      transplanted in size-matched recipients with a total mean ischemic time of 12 hr.
      The combined administration of SOD, CAT, DEF, insulin and glucose during the
      initial period of reperfusion had no beneficial effect on cardiopulmonary
      performance. A progressive fall in Pa O2 and mean aortic pressure was observed
      post-operatively in the 7 animals that were weaned from CPB. Five of them died
      within 3 to 5 hr after CPB weaning, the remaining 2 animals died of cardiac
      arrest within the fourth hour. The results of this experiment seem to indicate
      that: 1. better organ function and improved survival could have been obtained if
      the duration of anti-radical treatment had been prolonged after reperfusion and,
      2. physical manipulation of the donor grafts during harvesting and
      transplantation may have been partly responsible for the poor post
      transplantation cardiopulmonary performance.

PMID- 7717034
TI  - Ultramicroscope study of transplanted lungs in piglets.

PMID- 7717035
TI  - The optimal lung preservation solution: a challenge for the future?

PMID- 7717036
TI  - Tracheal transplantation: will new advances in surgical techniques unlock the
      door?

PMID- 7717038
TI  - The parabiotic model for the assessment of lung preservation--potential problems
      and solutions.

PMID- 7717037
TI  - Experimental researches on heart and lung preservation.
AB  - The purpose of these experimental researches was to study the physiopathology of
      heart and lung preservation. The current problem of the paucity of lung and heart
      lung donors can be solved either by retrieving the organs from cadavers or by
      increasing the time of preservation. Since the lung is more susceptible to
      ischemic injury if compared to the heart, we focused our studies on lung
      preservation techniques. Our results show that lung flushing prior to
      preservation is very important and the density and the potassium content of the
      solutions used for this purpose have to be chosen carefully. The addition of a
      surfactant precursor to the UW preservation solution maintained the pulmonary
      surfactant for at least 4 hrs of cold storage, but it failed to preserve lung
      ultrastructure for more than 4 hrs. The UW solution preserved heart
      ultrastructure for at least 6 hrs of cold-storage. Heat shock to induce the
      synthesis of heat shock proteins and catalse but failed to protect the heart from
      ischemia-reperfusion injury. The addition of vasoactive intestinal peptide (VIP)
      to the preservation solution maintained lung morphology and function upon 24 hrs
      of preservation and reperfusion and other authors showed that VIP protects the
      heart from ischemia-reperfusion injury. We are planning further investigations
      aiming to improve and extend the time of heart and lung preservation.

PMID- 7717039
TI  - A modified ex-vivo rabbit lung reperfusion model for the study of lung
      preservation techniques.
AB  - Extracorporeal reperfusion models have proved to be particularly useful for the
      experimental assessment of donor lung preservation techniques. One disadvantage
      of the models employed to date is what with the low reperfusion rates used, any
      minimal lung damage is compensated for and is thus not detected or at least not
      detected promptly. By permitting reperfusion at physiological flow rates, use of
      a membrane deoxygenator in a closed circuit permits early detection of damage due
      to ischaemia or reperfusion. A modified ex-vivo reperfusion model is presented
      which permits assessment of lung function under almost physiological conditions
      after varying periods of ischaemia and varying conditions of preservation.

PMID- 7717040
TI  - Reexpression of the neural cell adhesion molecule (NCAM) on cardiac myocytes in
      aging rat heart.
AB  - The neural cell adhesion molecules, NCAM, is present in several non-neuronal
      tissues including heart. Using biochemical methods it has been recently shown
      that NCAM is expressed on cardiac myocytes in early development. During postnatal
      development NCAM expression is down-regulated and is restricted to neural
      components of rat heart. However, in the aged rat heart NCAM expression is
      increased compared to young adult rats. In the present immunohistochemical study
      the localization of NCAM in different regions of aging rat heart was
      investigated. Cardiac myocytes expressed NCAM in newborn rat heart whereas NCAM
      was absent from myocytes in young adult heart. In aged rat heart, NCAM was
      reexpressed on cardiac myocytes in the ventricles. Thus, NCAM reexpression may be
      an element in regenerative processes or alternatively a marker of degenerating or
      dying myocytes.

PMID- 7717041
TI  - Enzyme histochemical studies of membrane proteases in rat subfornical organ.
AB  - Localization of membrane proteases glutamyl aminopeptidase (EAP), microsomal
      alanyl aminopeptidase (mAAP), dipeptidyl peptidase IV (DPP IV) and gamma-glutamyl
      transpeptidase (gamma-GTP) were studied in vessels of the rat subfornical organ
      (SFO), ependyma which cover the surface of the SFO, and adjacent brain
      structures. Results of enzyme histochemical reactions showed strong activity for
      EAP, mAAP, and gamma-GTP, but absence of DPP IV in microvessels of SFO. The
      ependyma which cover the SFO was positive for gamma-GTP, but negative for other
      studied proteases. Our results showed that the spectrum of enzymes in the
      majority of the vessels of SFO is similar to that of the microvessels of the
      adjacent brain tissue which were positive for EAP, mAAP, and gamma-GTP, but
      negative for DPP IV. The relative intensity of the enzyme reactions in vessels
      varied from central to lateral locations in the SFO and the adjacent brain
      tissue. There was also a difference in the relative reaction intensity from one
      enzyme to the other. The presence and heterogeneous distribution of the enzymes
      are consistent with the hypothesis that membrane proteases of the microvascular
      endothelium constitute an enzyme-barrier between blood and parenchyma of the SFO
      and between blood and brain tissue, and may be involved in metabolism or
      modulation of various peptides when they contact the plasma membrane of the
      endothelial cells of the vessels.

PMID- 7717042
TI  - Hypoplasia of G cells in long term steroid-treated rats after ultra-high dose of
      salmon calcitonin.
AB  - Male young adult Wistar rats were treated parenterally with cortisol and cortisol
      combined with salmon calcitonin for 28 and 56 days and the stomach was
      investigated histologically as well as the G cells using immunohistochemistry.
      After 28 days of cortisol administration desquamation of the superficial layers
      of gastric mucosa was found and after 56 days ulcer-like changes developed and
      increased gastrin immunoreactivity was observed. Administration of high doses of
      salmon calcitonin together with cortisol resulted in a significant hypoplasia of
      G cells and prevented the pathological changes in the gastric mucosa.

PMID- 7717043
TI  - Identification of sugar residues in secretory glycoconjugates of the lining and
      glandular epithelium of the chick embryo gizzard using lectin histochemistry.
AB  - Using seven horseradish peroxidase-conjugated lectins we studied the distribution
      of glycoconjugate sugar residues in the lining and glandular epithelium of the
      gizzard in chick embryos from day 7 to 21 of incubation. At the outer layer of
      the lining epithelium all investigated sugar residues were present from day 7
      onwards, except alpha-L-fucose, which was detected later. From day 9 some cells,
      which contained granules characterised by D-galactose-(beta 1--->3)-N-acetyl-D
      galactosamine and N-acetyl-D-glucosamine, were observed in the inner part of the
      lining epithelium. Afterwards, although in different time periods, all
      investigated oligosaccharides were detected in intercellular spaces filled with
      mucous material. At first, the cells of the anlage of the tubular glands appeared
      to be characterised by D-glucosamine and alpha-D-mannose only. Afterwards, all
      the investigated sugar residues were detected. At hatching, the luminal glandular
      secretion showed all investigated sugar residues, except alpha-L-fucose, which
      was typical for the early formation of the tubular glands. Our data suggest that
      during the development of the gizzard three time periods of mucous release can be
      distinguished.

PMID- 7717044
TI  - Binding patterns of mistletoe lectins I, II and III to microglia and Alzheimer
      plaque glycoproteins in human brains.
AB  - Glycoconjugates of microglial cells and in some cases those glycoconjugates
      present in the amyloid plaques in Alzheimer's disease in the cerebral cortex can
      be stained with a lectin from mistletoe (ML-I) using a labour-intensive and time
      consuming indirect immunoperoxidase technique. In order to simplify the staining
      method and to test the staining characteristics of the other recently isolated
      mistletoe lectins (ML-II, ML-III) biotinylated MLs I-III were used together with
      an avidin-alkaline phosphatase-complex for visualisation. Our findings indicate
      that this new improved technique can also be used for detection of microglial
      cells and is considerably faster than the old method. In addition to microglial
      cells, ML-I labelled plaque glycoproteins possibly indicating that
      glycoconjugates derived from microglia can be detected in plaques. In contrast to
      ML-I, both ML-II and ML-III did not stain microglial cells.

PMID- 7717045
TI  - Insulin-binding sites in the mouse deferent duct.
AB  - In vivo light microscopic autoradiography was used to demonstrate the presence of
      specific insulin-binding sites in the mouse deferent duct three min after
      intravenous injection of 125I-insulin with or without excess of unlabeled
      insulin. The studies showed high specific insulin binding in the endothelial
      cells of capillaries and certain fibroblasts of the lamina propria. In the
      epithelium, although the tall columnar cells were free of specific insulin
      binding, the basal cells had relatively high specific insulin binding. Because
      the deferent duct has been considered to exert certain effects on sperms, the
      presence of high specific insulin binding at these sites may provide further
      support for this concept.

PMID- 7717046
TI  - A panel of monoclonal antibodies to rat plectin: distinction by epitope mapping
      and immunoreactivity with different tissues and cell lines.
AB  - A panel of twelve monoclonal antibodies (mAbs) to plectin was analyzed to
      localize molecular epitopes and assess their utility for various
      immunotechniques. Based on staining patterns obtained by immunoblotting of
      proteolytic plectin fragments five groups of mAbs with spatially closely linked
      epitopes were distinguished. In combination with previous results obtained with
      recombinant mutant proteins, the epitopes of all mAbs could be shown to reside
      within three separated domains of plectin's rod domain. Immunoblot analyses of
      several different rat tissues and a number of cultured cell lines derived from
      various species, including rat, hamster, cow, mouse and man, revealed
      considerable variations in immunoreactivity of antibodies. Differences in mAb
      immunoreactivities were also revealed by immunofluorescence microscopy of
      different tissues and cultured cell lines. One third of the mAbs examined
      produced staining patterns that were indistinguishable from those generated by
      conventional rabbit antisera, confirming the widespread and highly divers
      cellular localization of plectin previously reported. Microinjection of several
      monoclonal antibodies into Rat 1 cells had no detectable effects on the structure
      and organization of plectin arrays or of other cytoskeletal filaments. This new
      collection of mAbs provides a more reliable tool for histological studies than
      previously available antisera and should be useful for studies of tissue and cell
      type specific functions of plectin domains in vivo and in vitro.

PMID- 7717047
TI  - Ultrastructural classification of the endocrine cells of the large intestine of
      the calf. Cytochemical evidence of the presence of Viallis's pre-EC cells.
AB  - GEP (Gastro-Entero-Pancreatic) endocrine cells were very numerous in the mucosal
      layer of the large intestine of the calf. Their frequence appeared to increase
      towards the distal portions of the gut. Endocrine cells were dispersed among
      epithelial cells lining intestinal glands and were frequently grouped together.
      Cellular shape was pyramidal or elongated; the cytoplasm was electron-lucent and
      contained highly characteristic secretory granules. Six different types of
      endocrine cells were identified on the basis of the ultrastructural aspect and
      cytochemical characteristics (silver-reactivity) of their secretory granules: EC,
      L, PP, A, D1 and D cells. EC and L cells were the most abundant in all
      localisations. They were especially numerous in the rectum. A subpopulation of EC
      cells was negative to Masson-Singh's reaction showing that they lack 5-HT. This
      observation enabled us to refer this latter cellular type to the "pre-EC" cells,
      described by Vialli as an earlier evolutive step of the EC cells population.
      Their presence in the calf gut might be linked to its possible "immaturity", due
      either to the age or to the alimentary diet.

PMID- 7717048
TI  - Profile of nurse anesthesia programs.
AB  - Over time, the Council on Accreditation of Nurse Anesthesia Educational Programs
      (COA) and the AANA Education and Research Department have recognized the need to
      gather information significant to nurse anesthesia programs. The need to create a
      formalized mechanism to gather and analyze information has also been identified
      as the profession has grown. COA and the Education and Research Department have
      responded to this need by creating a database and a reporting mechanism in order
      to present information to the Assembly of School Faculty at its annual meeting.
      The information will be summarized in this article, which is the first formal
      vehicle of disseminating the data.

PMID- 7717049
TI  - An exposure incident: the role of the anesthesia department.

PMID- 7717050
TI  - Status of AANA's four priorities in Senate and House leadership healthcare reform
      bills.

PMID- 7717051
TI  - Supervision.

PMID- 7717052
TI  - The healthcare information superhighway: are we ready?

PMID- 7717053
TI  - The intraoperative administration of ketorolac tromethamine in evaluating length
      of stay in a same day surgery unit.
AB  - This study was performed to determine if intraoperative administration of
      ketorolac tromethamine, a nonsteroidal anti-inflammatory drug, could shorten the
      length of stay in the same day surgery unit of a 535-bed medical center. Fifty
      laparoscopic patients were included in this study. Laparoscopic patients were
      chosen because they demonstrated an increased incidence of postoperative pain
      that delayed hospital discharge. The study population was divided into a test and
      control group. To eliminate procedural variability, the 50 subjects were chosen
      from a single group practice. Length of stay was recorded on a data retrieval
      form. Reasons for delay in discharge were identified. Subjects who received
      ketorolac tromethamine were discharged an average of 30 minutes earlier than
      those who did not receive it (94 minutes versus 124 minutes, respectively). A t
      test revealed this difference to be statistically significant (P < or = .004).
      Intraoperative administration of ketorolac tromethamine should be considered for
      laparoscopy patients in same day surgery units, because criteria for discharge,
      such as stable vital signs, minimal nausea or vomiting, minimal pain, and
      oriented x 3 with a stable gait, are met sooner.

PMID- 7717054
TI  - Emergent exploratory laparotomy for a patient with recent Guillain-Barre
      recurrence: a case report.
AB  - A case study is presented of a 20-year-old male with a recent exacerbation of
      Guillain-Barre syndrome who had an emergent exploratory laparotomy under general
      endotracheal anesthesia. His preoperative history and physical examination
      indicated complicating factors, including blunt abdominal trauma, ethanol
      ingestion, and a full stomach. The management of patients with Guillain-Barre
      syndrome and their special needs are discussed.

PMID- 7717055
TI  - Conscious awareness and memory during general anesthesia.
AB  - Conscious awareness is an infrequent complication of general anesthesia. All
      methods of anesthesia have been implicated, and no method guarantees amnesia.
      This article examines implicit and explicit memory and discusses factors
      associated with awareness. Common methods of detection are unreliable, and
      symptoms resembling post-traumatic stress disorder may result if awareness goes
      unrecognized and untreated. Patients who experience awareness may sue on grounds
      of malpractice, breach of contract, and lack of consent. Overhearing negative
      stimuli may affect patient outcome, because learning and language comprehension
      can occur during what appears to be clinically adequate anesthesia. Strategies to
      block threatening auditory stimuli include use of earphones, music tapes, white
      noise, reassuring statements, or positive suggestion. Behavioral anesthesia
      decreases patient stress to enhance recovery. Evidence of patient benefit
      resulting from therapeutic suggestion is inconclusive.

PMID- 7717056
TI  - AANA journal course: update for nurse anesthetists--current concepts in pediatric
      resuscitation.
AB  - The evolution of the current recommendations for pediatric cardiopulmonary
      resuscitation have slowly evolved following the development of cardiopulmonary
      resuscitation techniques for the adult patient. Anatomical and physiological
      differences along with the pathophysiology of pediatric cardiopulmonary arrest
      mandate special consideration when approaching pediatric cardiopulmonary
      resuscitation.

PMID- 7717057
TI  - Inhibition of [methyl-3H]diazepam binding to rat brain membranes in vitro by
      dinatin and skrofulein.
AB  - Two flavones, 4',5,7-trihydroxy-6-methoxy flavone (dinatin) and 4',5-dihydroxy-6,
      7-dimethoxy flavone (skrofulein), were extracted from Artemisia herba alba L.
      Dinatin and skrofulein inhibited the binding of [methyl-3H]diazepam to rat brain
      membranes in vitro with IC50 of 1.3 and 23 mumol.L-1, respectively. The GABA
      ratios (the ratio of IC50 values in the absence/presence of GABA in the binding
      assay) were 1.1 and 1.2 for dinatin and skrofulein, respectively. Both flavones
      induced a slight increase in [35S] TBPS binding. The data suggest that the
      flavones are antagonists or partial agonists of benzodiazepine receptors.

PMID- 7717058
TI  - Effects of 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin on myocardial
      dysfunction after a brief ischemia in anesthetized dogs.
AB  - The effect of a 30-min infusion of 3'-angeloyloxy-4'-acetoxy-3', 4'
      dihydroseselin (Pd-Ia), a coumarin isolated from Peucedanum praeruptorum Dunn
      0.15 mg.kg-1.min-1 on regional myocardial dysfunction was examined in 16
      anesthetized open-chest dogs subjected to a 15-min occlusion of the left anterior
      descending coronary artery followed by a 3-h reperfusion. Segment lengths of left
      ventricular wall were measured with an ultrasonic micrometer. The control caused
      a decrease in the % of segment shortening (SS%) throughout the reperfusion period
      (n = 8), while Pd-Ia ameliorated segment function immediately after reperfusion
      and restored the SS% to 41 +/- 51% of the baseline value (n = 8, P < 0.05 vs
      control) 5 min after reperfusion without any significant changes in
      cardiohemodynamics. The improvement of myocardial function induced by Pd-Ia was
      maintained at least 3 h after reperfusion. These findings revealed that Pd-Ia had
      a cardioprotective action in stunned myocardium.

PMID- 7717059
TI  - Effects of Panax notoginseng saponins on receptor-operated Ca2+ channels in
      vascular smooth muscle.
AB  - The effects of saponins of Panax notoginseng (PNGS) on the alpha-adrenoceptor
      agonists-induced contractile responses and Ca2+ movement were studied in dog
      mesenteric artery (MA) and saphenous vein (SV). PNGS reduced the contractions and
      the 45Ca influx (from 0.36 +/- 0.03 to 0.14 +/- 0.05 mumol.g-1 wet strip) induced
      by phenylephrine (Phe) without effect on KCl-induced contraction and 45Ca influx
      which were nearly completely inhibited by nifedipine 0.1 mumol.L-1. PNGS did not
      change the 45Ca efflux induced by Phe and the Kd value (from 0.76 +/- 0.04 to
      0.72 +/- 0.15 nmol.L-1) for [3H]prazosin binding on the microsomal membrane
      isolated from MA. Our results indicate that PNGS selectively inhibits Ca2+ entry
      through receptor-operated Ca2+ channel.

PMID- 7717060
TI  - Pharmacokinetic-pharmacodynamic modeling of electroencephalographic effects of
      midazolam in eight Chinese men.
AB  - The effects of midazolam (Mid) on the electroencephalogram (EEG) were related to
      Mid concentrations in serum in 8 Chinese healthy male volunteers for the
      assessment of concentration-effect relationship. The total number of waves per
      second within the frequency range of 12-30 Hz (TNW12-30) in the central-occipital
      (C1-O1) lead EEG obtained by aperiodic analysis was used as EEG effect of the
      drug. The PK-PD parameters were calculated by PK-PD software using the sigmoid
      Emax model. They were: T1(2)keo = 1.3 +/- 0.9 min-1, EC50 = 254 +/- 54
      micrograms.L-1, N = 2.9 +/- 0.6. E0 and Emax were calculated from the observed
      values, being 3.4 +/- 1.3 and 11.4 +/- 2.2 TNW12-30, respectively. Our results
      showed that the concentration-EEG effect relationship of Mid could be
      characterized in individual Chinese man using TNW12-30 as a measure of
      pharmacological response.

PMID- 7717061
TI  - Microprocessor-programmed infusion of theophylline rapidly attained expected
      steady-state level in rabbit plasma.
AB  - A self-made microprocessor-programmed (two-compartmental model) infusion
      controller was connected with an infusion pump, which achieved an expected steady
      state plasma concentration (Cpss) rapidly (5 T1(2)alpha) and maintained the
      level. Theophylline was selected as an example, and its pharmacokinetic
      parameters of rabbits, expected Cpss, body weight (wt), and infusion time (t)
      were input. The programmed infusion rate (Kt) was determined by the following
      equation: (Kt) = Cpss.K10.Vc.wt (1 + [(K21-beta)/beta]EXP(-K21t)) and the
      predicted value was calculated by the formula: C(t) = Cpss X [1-EXP(-alpha t)].
      The needed concentration and total volume of drug were automatically shown on the
      screen. The drug was automatically infused after pumping, and the plasma
      concentration of theophylline was measured by colorimetric method. The results
      showed that the median absolute value of the performance error (MAVPE) was 8.3%.
      Although T1(2)beta of theophylline was 6.08 h, the expected Cpss was attained in
      only 30 min (5 T1(2)alpha) after start of infusion and then well maintained.

PMID- 7717062
TI  - Protective effect of tetramethylpyrazine against damages of aortic endothelial
      cells elicited by low-density lipoproteins.
AB  - Effects of tetramethylpyrazine (TMP) on endothelial cells damaged by low-density
      lipoproteins (LDL) were investigated. When endothelial cells were incubated with
      LDL (1.5 mg protein.ml-1) the level of malondialdehyde (MDA) was increased and
      the activity of superoxide dismutase (SOD) was inhibited, and levels of cGMP and
      epoprostenol were decreased. TMP at concentrations of both 20 and 150 mg.L-1
      nullified the inhibition of SOD activity and the reduction of cGMP and
      epoprostenol content elicited by LDL. However, the elevation of MDA content
      induced by LDL was negated by TMP only at 150 mg.L-1. TMP also caused a reduction
      in MDA content and an increase of epoprostenol level in normal endothelial cells.
      This study suggests that TMP protects endothelial cells against damages elicited
      by LDL and that the protection of TMP might be due to reduction in lipid
      peroxidation through stimulation of production and/or release of epoprostenol.

PMID- 7717063
TI  - Pharmacokinetics of ofloxacin through three administration routes.
AB  - This paper reports the pharmacokinetic characteristics of ofloxacin (Ofl) through
      3 administration routes in 42 patients with respiratory tract infections. The
      concentration-time data were fitted with a two-compartment model for infusion
      (inf) and im, and a one-compartment model for po. The pharmacokinetic parameters
      of Ofl through inf, im and po were: T1/2 beta or T1/2K 6.0 +/- 1.3, 5.0 +/- 1.0,
      and 5.0 +/- 0.7 h; Vc or Vd 58 +/- 16, 68 +/- 27 and 94 +/- 25 L; Cmax 3.9 +/-
      1.0, 2.8 +/- 0.9, and 1.9 +/- 0.7 micrograms.ml-1; AUC 16 +/- 5, 15 +/- 4, and 15
      +/- 4 h.micrograms.ml-1; Cl 13 +/- 4, 14 +/- 4, and 14 +/- 3 L.h-1, respectively.

PMID- 7717064
TI  - Effects of quercetin on Na(+)-K(+)-exchanging ATPase and Ca(2+) Mg(2+)-ATPase in
      rats.
AB  - Quercetin (Que) ig 200 mg.kg-1, qd x 14 d decreased activities of the Na(+)-K(+)
      exchanging ATPase (I) of rat brain plasma membranes and heart sarcolemmal and
      Ca(2+) Mg(2+)-ATPase (II) of heart sarcolemmal membrane. Que 100 mg.kg-1 reduced
      the activity of I from rat heart sarcolemmal preparation, but had no effect on
      that from rat brain plasma membranes. The result shows that I of myocardium is
      more sensitive than that of brain in rat. Que also showed a remarkable inhibitory
      effect in the II of heart sarcolemma.

PMID- 7717065
TI  - Comparison of dopexamine hydrochloride, fenoldopam, and procaterol on myocardial
      nutritional flow in rats.
AB  - Myocardial nutritional flow (MNF) was determined using 99mTechnetium-methoxy
      isobutyl-isonitrile (99mTc-MIBI) in rats. At 25 nmol.kg-1, dopexamine
      hydrochloride (DH), fenoldopam, and procaterol increased the uptake rate of 99mTc
      MIBI/g myocardium by 80.8 +/- 10.2% (P < 0.01), 44.9 +/- 6.3% (P < 0.05), and
      30.2 +/- 5.4% (P < 0.05) respectively. These findings suggested the potential
      advantages of DH over other dopaminergic agonists in the treatment of coronary
      disease.

PMID- 7717066
TI  - Protection of bradykinin on neonatal rat myocytes subjected to
      anoxia/reoxygenation injury.
AB  - This study was to investigate the effects of bradykinin (BK) on myocyte cultures.
      The effects of BK against lipid peroxidation and oxygen free radicals were
      estimated on an anoxia/reoxygenation injured model. A salicylate hydroxylation
      product dihydroxybenzoic acids (DHBA) was detected using HPLC with
      electrochemical detection, a sensitive device for assaying the hydroxyl free
      radical. BK (10 nmol.L-1) reduced thiobarbituric acid reactive substances (TBARS,
      from 1.94 +/- s 0.28 to 0.25 +/- 0.03 nmol/10(6) cells, n = 5, P < 0.01), lactate
      dehydrogenase (LDH) release (1.28 +/- 0.23 to 0.63 +/- 0.12 u.ml-1, n = 8, P <
      0.01) and DHBA (60 +/- 5 to 44 +/- 12 nmol.L-1, n = 6, P < 0.01). These
      improvements were nullified by pretreatment with K86/4321 (1 mumol.L-1), a kind
      of BK receptor antagonist. Indometacin (Ind, 1 mumol.L-1) had a synergic action
      with BK to decrease the LDH release, but Ind (30 mumol.L-1) attenuated the
      protection of BK, while both LDH and TBARS were increased. The mechanism for
      protection of BK was ascribable to the activation of BK receptor, the inhibition
      of lipid peroxidation, and the decreased hydroxyl free radical formation.

PMID- 7717067
TI  - Restoration of intracellular drug accumulation in MDR cell line K562r does not
      mean reversal of its drug resistance.
AB  - Our purpose was to test whether drug sensitivity and drug accumulation in MDR
      cell erythroleukemic K562r could be restored by incubating cells with 3
      anthracycline antibiotics in combination. Drug sensitivities of cells were
      assessed with MTT assay, in which doxorubicin, epirubicin, daunorubicin, or the 3
      drug mixture was applied with concentrations ranging from 1 to 3125 ng.ml-1. The
      IC50 of K562r cells were 1.0, 1.0, 0.1, and 0.2 microgram.ml-1, respectively,
      about 22, 16, 10, and 20 times higher than those of K562 cells. After cells were
      exposed to doxorubicin (2-32 micrograms.ml-1) for 1 h, the drug concentrations in
      K562r cells were all higher than those in K562 cells. Similar results were
      obtained for epirubicin or daunorubicin. After 1-h incubation of cells with the 3
      drug mixture (3 to 192 micrograms.ml-1), there were no considerable differences
      of drug accumulation between K562r and K562 cells with only 3 exceptions in 21
      groups. It is concluded that restoration of intracellular drug accumulation in
      MDR cell line K562r was not correlated with reversal of its drug resistances.

PMID- 7717069
TI  - Flow dependence of metoprolol elimination in isolated perfused rat liver.
AB  - The effect of blood flow rates on hepatic elimination of metoprolol (Met) was
      studied in a recirculating isolated perfused rat liver system with a constant
      infusion of Met into the reservoir. This design ensures that, at a steady state,
      the elimination rate of Met is a constant. The results showed that at flow rates
      of 10, 20, and 30 ml.min-1, the concentrations of Met entering the liver (Cin)
      were 7.6, 5.0, and 3.4 micrograms.ml-1 and the concentrations leaving the liver
      (Cout) were 1.2, 2.0, and 2.7 micrograms.ml-1, while the logarithmic average
      concentrations in hepatocytes (C) were 3.4, 3.2, and 3.0 micrograms.ml-1,
      respectively. It is concluded that the hepatic elimination of Met is flow
      dependent, which is in accordance with the 'parallel tube' model.

PMID- 7717068
TI  - Protein c-fos induction in rat brain and spinal dorsal horn by sincalide and
      opioids in vitro.
AB  - Sincalide (CCK-8) is an antiopioid substance. In this study, we investigated the
      effects of sincalide and opioids on c-fos expression and their interaction in
      brain and spinal dorsal horn in vitro. Immunoprecipitation was used for detection
      of c-fos protein. The results indicated that 0.1 mumol.L-1 sincalide induced c
      fos expression markedly in both brain (a 3.8-fold increase in c-fos protein
      level) and in spinal dorsal horn (a 3.6-fold increase). NDAP (a kappa receptor
      agonist) 0.1 mumol.L-1 showed some activating effects on c-fos expression, the c
      fos protein level increased 2.7 and 2.6 times respectively in brain and spinal
      dorsal horn. Ohmefentanyl (Ohm, a mu receptor agonist) 0.1 mumol.L-1 also
      exhibited an inducing effect on c-fos protein production. Sincalide and NDAP
      exerted some additive effects on c-fos protein production in spinal cord. In
      contrast, the effect of sincalide on c-fos protein production is antagonistic to
      that of Ohm. The results suggested that there were changing patterns of
      interaction on c-fos expression between sincalide and opioids.

PMID- 7717070
TI  - Platelet activation by platelet aggregation factor from Eisenia foelide.
AB  - A platelet activating factor from earthworm, Eisenia foelide (EPAF, 25.9 mumol.L
      1), induced human platelet aggregation and 5-HT (maximal release of 89% at EPAF
      74.1 mumol.L-1) was detected during this process. Neither creatine
      phosphate/creatine phosphate kinase (CP/CPK) nor aspirin completely inhibited the
      EPAF-induced platelet aggregation. In the presence of fibrinogen, EPAF (55.6
      mumol.L-1) induced the aggregation of human platelet which had been thrombin
      treated and degranulated. Results indicated that EPAF was a potent platelet
      agonist and the EPAF-induced platelet aggregation was ADP- and TXA2-independent.

PMID- 7717071
TI  - Effects of alloxan on electric activity of mouse pancreatic B cells in vitro.
AB  - Microelectrode method for recording membrane potentials was used. It was observed
      that alloxan possessed stimulative and toxic dual effects on the electric
      activity of pancreatic B cells. A 10-min exposure to alloxan 14 mmol.L-1 in the
      perfusion medium without glucose caused a significant depolarization of B cells
      from -44 +/- 13 mV to -36 +/- 12 mV (n = 7, P < 0.05) and evoked spikes in B
      cells. But the spikes disappeared at 24 +/- 12 min (n = 8). In the presence of
      glucose 5.5 mmol.L-1 or 11.0 mmol.L-1, the dual effects became weaker or not
      obvious. After 10-min exposure to diazoxide (an ATP sensitive K+ channel opener)
      0.8 mmol.L-1 in the perfusion medium with alloxan 14 mmol.L-1 but devoid of
      glucose, the amplitude of membrane potential went up from -31 +/- 11 mV to -48 +/
      21 mV and the mean value of spikes dropped from 31 +/- 24 spikes.min-1 to 5 +/-
      5 spikes.min-1. It was suggested that the stimulative effect of alloxan was due
      to blocking of ATP sensitive K+ channel and a higher concentration of glucose
      could prevent B cells from alloxan injury.

PMID- 7717072
TI  - Effect of dipfluzine on platelet aggregation and thrombus formation.
AB  - Dipfluzine (Dip) is a novel diphenylpiperazine calcium channel blocker first
      synthesized in China. Effects of Dip on experimental thrombosis and platelet
      aggregation were studied in vitro and in vivo compared with cinnarizine (Cin).
      Dip 1 and 2 mg.kg-1 i.v. and incubated in 1-100 mumol.L-1 in vitro inhibited dose
      or concentration-dependent rabbit platelet aggregation induced by ADP and by
      arachidonic acid (AA), respectively. Dip 2.5-10 mg.kg-1 i.v. and 50-100 mg.kg-1
      ip inhibited the thrombosis in rats. Dip 10 mg.kg-1 i.v. and 200 mumol.L-1
      depressed the in vitro thrombosis. These results suggest that attenuation of
      disturbed platelet-vessel wall reaction associated with platelet activation and
      vasoconstriction may be a main factor involved in the antithrombotic action of
      Dip, and that the effects of Dip were more potent than those of Cin.

PMID- 7717073
TI  - Early treatment of schistosomal infection with artemether and praziquantel in
      rabbits.
AB  - Artemether (Art, beta-methyl ether of artemisinin) first synthesized by Shanghai
      Institute of Materia Medica, Chinese Academy of Sciences, is effective against
      not only malaria but also schistosomiasis. When rabbits infected with Schistosoma
      japonicum cercariae for 7 d were treated ig with Art 10 mg.kg-1, the total worm
      reduction rates were 74.6-76.7%. If Art (10 mg.kg-1) was given once weekly after
      the first treatment for 3-4 times, the total worm reduction rate was > 98%, and
      most of the rabbits were free from female worms. When praziquantel (Pra) was
      given ig 40 mg.kg-1 to rabbits on d 21 after infection, and repeated once every
      week for 3 wk, most rabbits showed a total worm reduction rate > 98% with their
      livers showing normal or mild changes, and their parameters relevant to acute
      schistosomiasis were negative as compared to the controls. Hence Art and Pra are
      suggested to be used in field trial for control of acute schistosomiasis or
      reduction of the intensity of schistosomal infection.

PMID- 7717074
TI  - [Effect of verapamil on Ca2+ and Ca(2+) Mg(2+)-ATPase activity in rat brain
      synaptosomes].
AB  - To elicit the correlation between the adrenergic transmitter release and
      calmodulin (CaM), the effect of verapamil on the free Ca2+ concentration was
      measured with fluorescence analysis and Ca(2+) Mg(2+)-ATPase activity in rat
      synaptosomes were studied. When stimulated with high-K+ or norepinephrine, the
      concentration of free Ca2+ in rat synaptosome was increased by verapamil 10, 50,
      and 100 mumol.L-1. But the free Ca2+ concentration in the resting synaptosome was
      reduced by verapamil. The activity of Ca(2+) Mg(2+)-ATPase in synaptosome was
      remarkably inhibited by verapamil in a dose-dependent manner. These results
      support our hypothesis that CaM not only acts directly on the vesicles to enhance
      the transmitter release, but also acts on the activity of Ca(2+) Mg(2+)-ATPase to
      reduce the free Ca2+ in the cytosol, and indirectly inhibited the transmitter
      release.

PMID- 7717075
TI  - [Effects of morphine, pethidine and fentanyl on isolated rabbit trachea].
AB  - Effects of morphine, pethidine and fentanyl on tension of isolated rabbit trachea
      were measured by electric field stimulation. Findings obtained were: 1) Morphine
      53 mumol.L-1 increased markedly the trachea contraction (P < 0.01); 2) Fentanyl
      1.9 mumol.L-1 decreased the trachea contraction (P < 0.05); 3) Pethidine 705
      mumol.L-1 not only decreased markedly the trachea contraction (P < 0.01), but
      also relaxed the trachea; 4) Naloxone 2.2 mumol.L-1 had no influence on the
      trachea directly (P > 0.05), but reversed the effect of morphine on the trachea.
      The results indicated that the excitation of morphine receptor in trachea may be
      one of the mechanisms of the contraction of the trachea.

PMID- 7717076
TI  - [A reversed-phase HPLC method for determining tretinoin].
AB  - Tretinoin (Tre) and its active stereo isomer isotretinoin (Iso) were
      simultaneously determined by reversed-phase high pressure liquid chromatographic
      method with a uv detector adjusted to 348 nm. Separation was accomplished on YWG
      C18 column by using a MeOH:NH4Ac buffer (pH 6.0) 85:15 (vol:vol), chlorpromazine
      (Chl) being chosen as internal standard. Minimal detectable amount of Tre was 0.5
      ng. Calibration curve was linear (r = 0.9999) in the concentration range of 25
      2500 ng.ml-1. This method was used to determinate the transdermal amounts of Tre
      from three different preparations in Franz diffusion cell in vitro. The results
      showed that the proposed method could distinguish the transdermal differences
      from various formulations or different skin samples. In addition, it is able to
      be used in quantitative analysis of Tre and Iso.

PMID- 7717077
TI  - [Effects of furyl-dihydropyridine I on coronary collateral circulation in
      myocardial infarction of dogs].
AB  - Effects of furyl-dihydropyridine I (FDP-1) on collateral circulation were
      observed in ischemic myocardium of dogs. FDP-1 (200 micrograms.kg-1) of
      intracoronary injection increased collateral flow, reduced systemic artery
      resistance, and coronary systolic pressure in infarcted region and the area of
      infarction decreased from 28.9 +/- 1.3% to 15.3 +/- 1.2% (P < 0.01, n = 6). The
      results indicated that FDP-1 could improve coronary collateral circulation,
      increase collateral flow in ischemic region, decrease collateral flow in ischemic
      region, decrease myocardial oxygen demand, and protect myocardial ischemia.

PMID- 7717078
TI  - [Effects of m-nisoldipine on arterial baroreflex sensitivity in anesthetized
      rats].
AB  - Baroreflex sensitivity (BRS) in anesthetized rats was measured as the slope of
      the regression line of the concomitant maximal change in heart rate (delta R-R)
      and blood pressure (delta BP) induced by bolus i.v. phenylephrine or sodium
      nitroprusside, m-nisoldipine (m-Nis) i.v. 5, 10, 20 micrograms.kg-1 depressed the
      BRS (2.6 +/- 0.2, 2.4 +/- 0.3, 1.6 +/- 0.2, or 1.7 +/- 0.1, 1.6 +/- 0.2, and 1.4
      +/- 0.2 ms.kPa-1, respectively) compared with before medication (P < 0.01). m-Nis
      may act directly on carotid sinus to depress the BRS, but not through cardiac
      beta or M receptor nor through central nervous system.

PMID- 7717079
TI  - [Effects of sodium diethyldithiocarbamate on ischemia-reperfusion-induced brain
      injury in Mongolian gerbil].
AB  - Brain injury in Mongolian gerbil (Merisones unguiculatus) was induced by
      occluding bilateral common carotid arteries for 60 min followed by reperfusion
      for 5 or 30 min. Oxygen free radicals in brain tissue were measured by electron
      spin resonance (ESR) technique, malondialdehyde (MDA) was measured by
      fluorescence spectrometry, and superoxide dismutase (SOD) was measured by nitrite
      kit. Oxygen free radicals and MDA were not significantly increased, but
      activities of T-SOD and Mn-SOD were decreased after 60 min of cerebral ischemia.
      The free radicals were increased at 5-min reperfusion, and then reduced to the
      level of ischemia group after 30-min reperfusion. MDA was increased remarkably
      after reperfusion of 30 min, whereas the activity of SOD continued to decrease.
      Sodium diethyldithiocarbamate (DTC), i.v. 5-100 mg.kg-1 15 min before occlusion,
      decreased the production of MDA and increased the activities of T-SOD and Mn-SOD.
      The formation of oxygen free radicals was depressed by i.v. DTC 50 mg.kg-1. The
      result suggested that the protective effects of DTC on ischemia-reperfusion
      induced brain injury might be induced by scavenging the oxygen free radicals,
      increasing the Mn-SOD activity and decreasing the production of MDA.

PMID- 7717080
TI  - [Suppressive effects of adenosine on nonspecific and humoral immunities in mice].
AB  - Adenosine (Ade) 1.3, 13, 130 mg.kg-1 ip inhibited the ability of peripheral
      leukocytes and peritoneal macrophages in phagocytosing the Staphylococcus albus
      with [3H]TdR incorporation in mice, declined the hemolytic ability of plaque
      forming cells and the production of antibody in mice immunized by sheep
      erythrocytes. Ade 13, 130 mg.kg-1 ip decreased the mouse serum muramidase
      (lysozyme) concentration. Dipyridamole (Dip) 10 mg.kg-1 ip attenuated the effects
      of Ade 130 mg.kg-1 on humoral immunity reaction, but the nonspecific immunity was
      not attenuated. These results showed that the uptake of Ade may play an important
      role in the effects of Ade on humoral immunity reaction. Aminophylline (Ami) 100
      mg.kg-1 ip attenuated the effects of Ade 130 mg.kg-1 on hemolytic ability of
      plaque-forming cells and the ability of peripheral leukocytes in phagocytosing
      Staphylococcus albus. These results suggested that the effects of Ade on murine
      humoral and nonspecific immunity reaction were mediated by Ade A2 receptor
      (A2DR).

PMID- 7717081
TI  - [Relationship between effect of tetrandrine on pleurisy and phospholipase A2].
AB  - A model of pleurisy was established with an intrapleural injection of carrageenan
      (Car, 10 mg.kg-1) in rats to explore the anti-inflammatory action of tetrandrine
      (Tet) and its mechanism. After the injection of Car, the exudate, protein and
      neutrophils appeared in the pleural cavity of rats at 2 h, then increased
      progressively, and reached a peak level at 12 h and remained high up to 48 h. The
      phospholipase A2(PLA2) activity of neutrophils (Neu-PLA2) and of the acellular
      component (ACC-PLA2) in the pleural exudate intensified at 2 h, rose to maximal
      intensity at 8 h, and started to decline at 48 h. The changes of the amount of
      exudate, protein content and neutrophil count, and parameters indicating the
      inflammatory response, were closely related to that of the PLA2 activity (r =
      0.749-0.928, P < 0.05 or 0.01). By ig gavage of Tet (10-80 mg.kg-1) to rats at 30
      min before and 4 h after the injection of Car, the inflammatory parameters were
      reduced and the PLA2 activity was inhibited, dose-dependently. The reductions of
      the inflammatory parameters were significantly associated with the inhibition of
      the PLA2 activity (r = 0.928-0.993, P < 0.05 or 0.01). These results indicate
      that Tet has a fine anti-inflammatory action and its mechanism may involve the
      inhibition on the activation and release of PLA2 of inflammatory cells.

PMID- 7717082
TI  - Effects of glucocorticoid treatment of the carbonic anhydrase activity of brain
      tissue in the early postnatal age in the rat.
AB  - The carbonic anhydrase activity in the brain tissue shows a considerable increase
      with proceeding gliogenesis during the first three postnatal weeks in the rat.
      The administration of 10 to 30 micrograms corticosterone or 5 to 10 micrograms
      dexamethasone per g body weight to 3-day old rats produced a marked acceleration
      in maturation of enzyme activity in the neocortex and hippocampus. The
      noradrenaline-induced stimulation of enzyme activity under in vitro conditions
      was also enhanced in corticosterone pretreated rats. There was no difference
      between the influence of noradrenaline and cAMP on stimulation of enzyme activity
      in either control or glucocorticoid-pretreated rats. In contrast to the
      corticosterone, the pretreatment with dexamethasone failed to stimulate the
      noradrenaline or cAMP effects on enzyme activity which may be due to differences
      in receptor-mediated responses for glucocorticoids. The glucocorticoid-induced
      acceleration of enzyme activity in the early postnatal period may be attributed
      to an enhanced development of glial elements.

PMID- 7717083
TI  - Facilitation of reentry by lidocaine in canine myocardial infarction.
AB  - Despite continuing controversies regarding its antiarrhythmic and
      antifibrillatory efficacy lidocaine is frequently used for the treatment of
      ventricular arrhythmias occurring in the early phase of acute myocardial
      infarction (MI). The authors studied the effects of lidocaine in 18 consecutive
      MI dogs 1-4 days (2.8 +/- 0.3 day) after the two-stage left anterior descending
      coronary artery (LAD) ligation and in 11 dogs, in which the LAD and the distal
      branches of the left circumflex artery was ligated 12-75 (mean 35) days prior to
      study. Electrophysiologic testing was performed in anesthetized post-infarction
      dogs using single, double or triple programmed extrastimuli or rapid bursts (3
      beats at 240-420/min) delivered to the right ventricular outflow tract.
      Inducibility of SMVT (uniform QRS morphology lasting > 30 sec at a rate of > 250
      beat/min) after an i.v. bolus of lidocaine (3-6 mg/kg) was compared in the same
      animal to the pre-drug state. During the control state, SMVT was inducible in
      6/18 dogs. After the administration of lidocaine, electrically induced SMVT was
      initiated in additionally 9 dogs (which were previously non-inducible; post
      lidocaine vs control p < 0.02). Sustained reentry was induced by 3 mg/kg
      lidocaine in 5 dogs (310 +/- 62 beat/min) and by 6 mg/kg in 4 (261 +/- 52
      beat/min). In the 8 survivors of the chronic MI group, SMVT was inducible before
      lidocaine administration in one, but in 7 after lidocaine. The antiarrhythmic
      agent induced further rate-dependent slowing of conduction in the peri-infarction
      subepicardium, which at a critical value of rate and amount of conduction delay
      resulted in sustained reentrant monomorphic tachycardia. These results show that
      lidocaine has arrhythmogenic/proarrhythmic actions in these canine models of MI
      probably due to its depressant effect on moderately sick cardiac tissue. The
      'modification' of the functional properties of the arrhythmia substrate by
      lidocaine can promote the formation of new reentrant pathways leading to manifest
      sustained ventricular reentry under electrophysiologic study.

PMID- 7717084
TI  - The renal actions of adenosine.
AB  - This study examined the effects of adenosine on the renal function. In ten normal
      dogs intrarenal adenosine infusion (20 nmol/kg/min) increased the renal blood
      flow (RBF) from 521 +/- 20 ml/min to 582 +/- 23 ml/min. The extraction of PAH
      (EPAH) decreased from 0.85 +/- 0.02 to 0.79 +/- 0.02, the Einulin from 0.24 +/-
      0.02 to 0.18 +/- 0.02. We conclude that the intrarenal infusion of adenosine
      modifies the intrarenal redistribution of the blood flow increasing the deep
      cortical and medullary blood flow. In these experiments the glomerular filtration
      (GFR) during adenosine infusion calculated from the extraction of the inulin
      (Einulin) multiplied by the renal plasma flow (RPF) decreased from 79.4 +/- 6.4
      ml/min to 62.2 +/- 6.6 ml/min and calculated from the Ecreatinine x RPF from 80.3
      +/- 6.3 ml/min to 59.3 +/- 4.9 ml/min. The EPAH x RPF did not change, it was 241
      +/- 11 ml/min and 253 +/- 13 ml/min, respectively. While the urinary clearances
      (the clearance calculated by the classic clearance formula; urinary concentration
      of the substance multiplied by the urine volume and divided by the plasma
      concentration) in the control periods did not differ from the direct clearances
      (Cinulin = 73.3 +/- 3 ml/min, Ccreatinine = 75 +/- 4 ml/min and CPAH = 262 +/- 15
      ml/min) during the adenosine infusion there are considerable differences: the
      Cinulin = 40 +/- 6 ml/min, the Ccreatine = 42 +/- 6 ml/min and the CPAH = 164 +/-
      22 ml/min. The differences are mathematically significant (p < 0.01). During the
      postinfusion periods the urinary clearances did not differ from the direct
      clearances. These results show that during adenosine infusion there is a
      definitive loss of the clearance substances somewhere in the nephron between the
      glomeruli and the pyelon. These observations suggest that during adenosine
      infusion there is a back-diffusion of the clearance substances because the
      permeability of the tubuli changes in the medullary part. The rediffused
      substances will be retransported into the circulation by the renal lymph flow and
      that is why they do not appear in the renal venous blood. The rediffusion can
      explain that the intrarenal adenosine infusion decreases considerably the
      excretion of the sodium and water in the kidney when there is no or only a small
      reduction of the glomerular filtration rate.

PMID- 7717085
TI  - Alterations in malondialdehyde concentration of jugular vein blood following
      transient brain ischemia. The effect of lactic acidosis.
AB  - Ischemia was induced for 10 min with a subsequent 60-min reperfusion and the
      changes of the malondialdehyde (MDA) concentration in the blood samples from the
      jugular vein were investigated in normo- and hyperglycemic dogs. Selective brain
      ischemia was evoked by the increase in cerebrospinal fluid (CSF) pressure. The
      experiments were carried out in 4 experimental groups. In sham operated animals
      (Group I) the blood MDA concentration did not change. The venous blood MDA
      content significantly elevated for 10 min after the start of reperfusion in
      normoglycemic animals (Group II). To study the effect of acidosis during ischemia
      and reperfusion on brain lipid peroxidation (LP) processes 1 and 2 g/kg glucose
      infusion was used in Groups III and IV. As an effect of ischemic lactic acidosis
      due to hyperglycemia the elevation of MDA concentration in the jugular vein blood
      was higher and it lasted longer than in the cases of normoglycemia. This finding
      supports the hypothesis that free radical reactions and LP processes play an
      important role in the enhanced brain damage caused by tissue acidosis.

PMID- 7717086
TI  - Formation of leucyl-leucine-O-methylester in leucine-O-methylester treated cells.
AB  - Porcine polymorphonuclear cells (PMN) and murine macrophages (M phi) were treated
      in vitro with Leu-OMe or Leu-Leu-OMe (1.5-5.0 mM) for various periods of time. It
      was found that the Leu-OMe and Leu-Leu-OMe entered cells rapidly, concomitantly
      the intracellular leucine accumulated. The methyl derivative diffused faster than
      Leucine due to its lipophylic character. The Leucine-O-methylesters hydrolysed
      rapidly as a consequence of the esterase and peptidase activities. The cells
      treated with Leu-OMe accumulated a high amount of Leucine and some Leu-Leu-OMe
      too. It was found that the formation of the didpeptide-methylester is not a
      spontaneous process, rather an enzymatic one. The Leu-OMe treated cells serve as
      a model which can be used to investigate the effect of the amino acid metabolism
      and the formation of dipeptides intracellularly and extracellularly.

PMID- 7717087
TI  - The influence of 1-month sex hormones administration on the isolated rabbit
      vessels reactivity.
AB  - Hyperestrogenemia and change in the estrogen-androgen level ratio in men are
      supposed to be possible risk factors for several cardiovascular diseases. To
      study the male rabbit spiral strip reactivity (aorta, renal artery, femoral
      artery) after 1-month sex hormone administration (estradiol or testosterone twice
      per week) the method of isomeric contraction was used. The maximal response to
      noradrenaline, 5-hydroxytryptamine (5-HT) and angiotensin was evaluated. Using
      RIA method the estradiol and testosterone levels in serum were examined. The
      estradiol application caused a significant increase of the estradiol level in
      serum with decrease of testosterone level. The increase of the maximal aorta
      response to noradrenaline and renal artery response to 5-TH was simultaneously
      observed. After the testosterone administration an increase of the testosterone
      level in serum, but without significant change in estradiol level was found. The
      inhibitory effect of testosterone on the femoral artery was shown by the decrease
      of the response to 5-HT and angiotensin.

PMID- 7717088
TI  - Is a complete recovery of diabetes mellitus possible?
AB  - Serum contains a factor that can normalize streptozotocin induced blood sugar
      elevation. This normalization can last for a long period. Thus an elimination of
      elevated diabetic blood sugar values takes place. This means that an euglycemic
      factor may have the ability to an eventual curing of diabetes. Normal, starving
      rats are not influenced by the euglycemic factor. An other factor even aggravates
      diabetic blood sugar level.

PMID- 7717089
TI  - Different effects of naproxen on the organ blood flows in normo- and hypervolemic
      anaesthetized rats.
AB  - The effects of naproxen, an inhibitor of the enzyme cyclooxigenase (10 mg/kg
      i.v.) on the distribution of the cardiac output (CO) and on the intrarenal
      hemodynamics were investigated in normovolemic (free salt and water uptake till
      the beginning of experiment) and hypervolemic (with i.v. infusion of 50 ml 0.9%
      NaCl solution/kg/10 min) narcotized rats. The cardiac output was measured on the
      basis of he Stewart-Hamilton principle, the blood flow of the organs by the
      Sapirstein method. 86Rb was used as indicator. In hypervolemia, the blood
      pressure is the same, the cardiac output is higher (CO-normovolemia: 23.1 +/-
      7.04, CO-hypervolemia: 29.0 +/- 6.43 ml/min/100 g; p < 0.05) the total peripheral
      resistance (TPR) is lower (TPR-normovolemia: 40.0 +/- 9.39 R, TPR-hypervolemia:
      31.2 +/- 8.34 R, p < 0.05) than in normovolemic animals. In hypervolemia the
      vascular resistance of the investigated organs (heart, lungs, kidney, skin,
      muscle, liver, spleen, intestine) is also lower and the intrarenal blood flow
      shifts toward the medulla. One hour following the naproxen administration a) in
      normovolemia joining to a slightly decreased cardiac output and increased TPR,
      the vascular resistance of the skin (R-control: 85.1 +/- 32.7, R-naproxen: 161 +/
      57.4; p < 0.001) and of the skeletal muscle (R-control: 114 +/- 35.1, R
      naproxen: 190 +/- 81.9; p < 0.01) increases. The blood flow of the other organs
      and the intrarenal hemodynamics does not change under the effect of naproxen. b)
      in hypervolemia the general circulatory parameters (blood pressure, cardiac
      output, TPR) and the parameters of the organ circulation and intrarenal
      hemodynamics remain unchanged. The results suggest that in rats the prostanoid
      compounds (PGE2, PGI2, TXA2) a) can modify the blood flow of the skin and muscle
      in normovolemic animals, but they do not have any role in determining the blood
      flow of the other organs or the intrarenal distribution of blood flow. b) in
      hypervolemia they play no role in determining organ-, or intrarenal blood flow.
      The consequences of cyclooxygenaze enzyme inhibition--at least in the case of the
      organ blood flow--depend on the magnitude of sodium and water load in the
      organism.

PMID- 7717090
TI  - Relevance of reversible inhibitors of monoamine oxidase type A and of reuptake
      inhibition for noradrenaline turnover.
AB  - Noradrenaline (NA) and serotonin, monoamines that increase neurotransmission at
      the monoaminergic synapses, remain primary targets for antidepressant drugs. To
      help elucidate NA's role in the action of antidepressants, a model was set up
      allowing for a simulation of NA turnover under various conditions examining 3
      compartments: newly synthesized vesicular NA, released synaptic NA, and vesicular
      NA reuptake across neuronal membranes. We compared the influence of the
      reversible MAO inhibitor, moclobemide, and the NA reuptake inhibitor,
      desipramine, both useful in regaining baseline synaptic NA concentrations.
      Moclobemide appears less sensitive to fluctuations either in drug concentrations
      and/or physiological determinants of NA turnover; we conclude that it may
      influence brain function in a more regulatory way than reuptake inhibitors.

PMID- 7717091
TI  - Clinical efficacy of reversible and selective inhibitors of monoamine oxidase A
      in major depression.
AB  - This article reviews efficacy studies of the reversible selective inhibitor of
      monoamine oxidase A (MAO-A) moclobemide, which has now received extensive
      evaluation. Placebo-controlled trials have shown it clearly to be effective. In
      comparisons with tricyclic and similar antidepressants and with serotonin
      reuptake inhibitors, it has been found of equal efficacy to these standard drugs.
      Because of previous suggestions that older MAO inhibitors are particularly
      effective in depressions characterized as atypical, the effects in subtypes are
      of particular interest. The evidence indicates that moclobemide is effective in
      typical severe depression with melancholia rather than being limited to less
      typical subtypes.

PMID- 7717092
TI  - Reversible and selective inhibitors of monoamine oxidase A in the treatment of
      depressed elderly patients.
AB  - The treatment of depression in the elderly population needs a thorough and
      careful work-up and an aggressive therapeutic approach. Any treatment initiative
      in this population often becomes difficult because of accompanying physical
      illness, concomitant medication, possible degenerative changes in central nervous
      system and age-related altered metabolic status. Despite unevenness in research
      findings, pharmacological treatment remains the mainstay of management of
      depression among elderly people. Currently available antidepressants, although
      effective, are problematic because of the increased vulnerability of the elderly
      to side effects. Recent research efforts to improve the efficacy and safety of
      drug treatment of depression resulted in development of reversible and selective
      monoamine oxidase inhibitors of the isoenzyme A (RIMA), with antidepressant
      efficacy comparable to tricyclic antidepressants and newer generation
      antidepressants. RIMAs include moclobemide, brofaromine, toloxatone and
      cimoxatone. Moclobemide is the most investigated available RIMA for therapeutic
      use at present. Its absorption and disposition in elderly individuals do not
      differ significantly from those in young healthy volunteers and depressed
      patients. The results of present clinical studies show that, in elderly depressed
      patients, moclobemide is at least as effective as other antidepressants. Its
      particular advantage is, however, that it is as well tolerated in elderly people
      as in younger people. There are only few significant adverse events, and they are
      generally less frequent and less severe than those with TCAs. An additional
      attribute of moclobemide seems also to be its beneficial effect on cognitive
      functions.

PMID- 7717093
TI  - Studies of reversible and selective inhibitors of monoamine oxidase A in
      dysthymia.
AB  - Dysthymia is a relatively common disorder and is frequently associated with other
      mental conditions such as major depression and anxiety. A number of controlled
      and uncontrolled studies have indicated that conventional as well as more recent
      antidepressants such as moclobemide, a selective, reversible inhibitor of
      monoamine oxidase (MAOI), may be effective in dysthymia and dysthymia-like
      disorders. However, assessment of the results of previous studies is confounded
      by the relative lack of standards in diagnostic criteria, outcome measures,
      dosage and duration of treatment. Applying DSM-III-R criteria, the efficacy of
      moclobemide in dysthymia has been confirmed in a significant study from South
      America, and other comparable studies are under way. The potential role of
      selective, reversible MAOIs such as moclobemide can be more firmly established
      when results of additional investigations have become available.

PMID- 7717094
TI  - Reversible and selective inhibitors of monoamine oxidase A in mental and other
      disorders.
AB  - The clinically tested reversible inhibitors of monoamine oxidase A (RIMAs)
      include brofaromine, moclobemide and toloxatone. Moclobemide has shown
      unequivocal antidepressant activity against serious depressive illness in 4
      placebo-controlled double-blind trials. It has been compared with amitriptyline,
      imipramine, clomipramine, desipramine, maprotiline, fluoxetine, fluvoxamine,
      tranylcypromine, toloxatone, mianserin and amineptine in the treatment of
      depressive disorders. Meta-analysis showed convincing evidence of moclobemide
      efficacy, comparable with the most potent antidepressants available. The efficacy
      of moclobemide has been demonstrated in psychotic and non-psychotic depression,
      in depression with and without melancholia, in endogenous depression (both
      unipolar and bipolar), in retarded depression and in agitated depression. The
      efficacy of moclobemide, allied to the unusually benign side effect profile, has
      led to exploration of its use in other disorders. Two small studies have given
      encouraging results in the treatment of attention-deficit hyperactivity disorder.
      Large placebo-controlled studies have shown the activity of moclobemide in the
      depression that accompanies dementia (such as senile dementia of Alzheimer type).
      The results also suggested that, in this patient population, cognitive ability
      improved in parallel. Social phobia has also been shown to improve on treatment
      with either moclobemide or brofaromine. Clinical trials are in progress on the
      effect of moclobemide in chronic fatigue syndrome. Moreover, there are
      encouraging results with the use of brofaromine and moclobemide in panic
      disorder. Other disorders in which treatment with RIMA is of interest include
      agoraphobia, bulimia, borderline personality disorder, post-traumatic stress
      disorder, compulsive hair pulling (trichotillomania), dysmorphophobia,
      kleptomania as well as various anxiety syndromes.

PMID- 7717095
TI  - The advent of selective monoamine oxidase A inhibitor antidepressants devoid of
      the cheese reaction.

PMID- 7717097
TI  - [Aluminum and central nervous system].

PMID- 7717096
TI  - Pharmacology of reversible and selective inhibitors of monoamine oxidase type A.
AB  - The concept of reversible type A monoamine oxidase (MAO-A) inhibitors as
      effective antidepressant drugs with a minimal side effect profile has been
      vindicated in practice. Despite this, the pharmacological basis for their actions
      is unclear. Studies with the irreversible inhibitor clorgyline have shown that
      chronic but not acute treatment of rats leads to a significant enhancement of
      noradrenaline release from peripheral sympathetic nerves and cerebral cortex
      together with a more effective inhibition of MAO-A, as shown by reduction in
      levels of deaminated metabolites in cortical microdialysis fluid. Reversible
      inhibitors, however, do not have a cumulative effect on MAO inhibition and may
      have different effects on noradrenaline release. Reversible inhibitors did not
      produce the acute reduction in sympathetic nerve activity seen with clorgyline,
      which may be one factor in explaining their milder side effect profile. Other
      aspects of the pharmacology of reversible and irreversible selective inhibitors
      of MAO-A are reviewed.

PMID- 7717098
TI  - [The elderly at the General Hospital and liaison psychiatry].
AB  - It is known that in general hospitals there is an increasingly high percentage of
      elderly patients that frequently develop psychiatric morbidity during hospital
      stay. This has lead the authors to perform a comparative study involving patients
      referred to Consultation/Liaison Psychiatry, in order to establish guidelines for
      a future approach. The first 1.000 referrals to the Consultation/Liaison
      Psychiatry Unit of the Santa Maria Hospital were analysed by comparing patients
      aged 65 or above to other observed patients. The results indicate a clearly lower
      percentage of elderly patients referred and a longer average length of stay at
      the moment of referral. Medical diagnoses show a preponderance of cardiologic,
      malignant and respiratory diseases, whereas intoxication, the prime diagnosis in
      the younger group, is much less represented above the age of 65. Identically,
      referrals due to suicide attempt were significantly less frequent in this group.
      Psychiatric diagnoses show a greater prevalence of organic mental disorders,
      followed by mood disorders, while in the younger the latter prevail. The post
      discharge plan shows a higher percentage of elderly patients referred to general
      practitioners and medical specialties and a lower one for psychiatric care, as
      opposed to the younger group. The conclusions point towards the need for programs
      directed to early detection and treatment of psychopathological disorders
      (organic and depressive mental disorders) of elderly people admitted to a general
      hospital. This will be achieved through a close collaboration between C/L
      psychiatrists and medical staff, families and community facilities.

PMID- 7717099
TI  - [Children and lead exposure. Preliminary study].
AB  - Lead poisoning is one of the most common and preventable childhood illness. The
      authors believe that the present study is the first evaluation of this problem in
      Portugal. OBJECTIVES: a) to characterize blood lead levels in children aged 1 to
      6 years living in the Oporto area; b) to identify risk groups and develop
      screening strategies. MATERIAL AND METHODS: The authors studied an opportunistic
      sample of children that were observed at the Hospital Maria Pia and the Instituto
      Nacional de Saude Dr. Ricardo Jorge (Porto) to whom blood testing was requested.
      All children with neurological or digestive symptoms were excluded (October
      December 1991; n = 113). RESULTS: One child had a blood lead level of 46.6
      micrograms/dl (class-IV, CDC); 32% (n = 36) were between 20 e 44 micrograms/dl
      (class-III), while only four children (3.2%) presented values < = 9 micrograms/dl
      (class-I). Class II included the remainder (n = 73). The results clearly point
      out that lead poisoning is a real problem among Portuguese children, since the
      proportion of children not considered to be lead-poisoned is very small. Children
      in the other classes are at risk of developing acute and chronic toxicity.

PMID- 7717100
TI  - [Effect of aluminum on the non-enzymatic oxidation of dopamine].
AB  - The effect of different concentrations of aluminum sulphate on the nonenzymatic
      oxidation of dopamine was studied in order to evaluate the action of this metal
      on neuromelanin synthesis. Data shows that under the studied conditions, aluminum
      partially inhibits dopamine self-oxidation, decreasing the formation of some
      intermediate compounds, namely dopaminequinone and dopaminochrome. If
      neuromelanins have a cytoprotective function in the central nervous system,
      possibly acting as intracellular scavengers of free radicals and redox metal
      ions, their decrease due to aluminum could be responsible for serious damage to
      neuronal tissues.

PMID- 7717101
TI  - [Computerized tomography of the child's thorax. Clinical use].
AB  - The authors describe the use of Computed Tomography for the evaluation of
      pediatric patients, with a variety of chest diseases. Indications and technical
      factors are described according to the experience of the examinations done in the
      first 100 children studied in the Radiology Department of the Santa Maria
      Hospital.

PMID- 7717102
TI  - [Gestational herpes].

PMID- 7717103
TI  - [Ebstein's anomaly of the tricuspid valve. Clinical tolerance up to 38 years of
      age and pregnancy].
AB  - Ebstein's Anomaly of the tricuspid valve has a variable degree of abnormality
      with a continuous change between mild and severe forms and, consequently, a
      variable clinical course. Pregnancy can also be well tolerated with a good fetal
      outcome. The authors present a case of a 44 year old woman with Ebstein's Anomaly
      of the tricuspid valve. Clinical evolution to the age of 38 and two term
      pregnancies in the third decade of life were well tolerated. The infants were
      normal and had an adequate development.

PMID- 7717104
TI  - [Gastrointestinal angiodysplasia. Estrogen-progesterone therapy].

PMID- 7717105
TI  - [Antiphospholipid immunization syndrome and thrombosis].
AB  - The designation of Antiphospholipid Syndrome was first applied by Harris in 1987,
      to a clinical status characterized by the detection of anticardiolipin and/or
      lupus anticoagulant with clinical thromboembolic manifestations. Recent advances
      in its study has shown that the inducing antigen is really a complex of
      phospholipid and protein. Therefore, it became clear that there is a need for a
      protein cofactor to the formation and action of antiphospholipid antibodies
      (APL). The authors present a detailed revision of the nature and specificity of
      APL, described as its proteic counterpart. Their action is surely conditioned by
      the specific protein involved with phospholipids, as it may be with Beta 2
      Glycoprotein 1, Prothrombin, Protein c and s, Anexin V and the association of
      plasminogen and t-PA. The isotype of immunoglobulins is also very heterogeneous,
      since it was detected as IgG as well as IgA and IgM immunoglobulins. Furthermore,
      they can coexist in the same patient and with no clear relationship with
      thromboembolic manifestations. These aspects demonstrate well the greater
      variability that is found in these patients in relation to clinical and
      laboratory manifestations of the disease. For laboratory diagnosis, micro ELISA
      systems were developed, allowing the identification of antiphospholipid
      immunoglobulins with relative specificity and accuracy. Finally, the most
      frequent clinical expression is described, emphasising the pitfalls of clinical
      and laboratory diagnosis of the antiphospholipid syndrome.

PMID- 7717106
TI  - [Medical education: challenges for the future].
AB  - With the objective of contributing to the Reform of Medical Education, presently
      in progress in Portugal, this paper presents a short review of the main reasons
      to change, as well as international movements and pedagogical trends in Medical
      Education. Some specificities of medical education in Portugal are discussed and
      the main difficulties and strategies for change are addressed. The experience of
      the Karolinska Institute in Stockholm is reviewed and its potential correlations
      to the Portuguese situation are explored.

PMID- 7717107
TI  - [News on the trip and the diplomatic mission of a Portuguese ambassador to China
      in 1752. Critical and analytical study].
AB  - The author of this report has worked out a critical-analytical study, based on
      the news of a voyage to China, carried out by a Portuguese ambassador, which was
      also a diplomatic mission, in 1752, during the Marquis of Pombal era, Prime
      Minister of king Dom Jose I. This study is directed under two perspectives:
      medical and historical-diplomatic. The former not only allows the assessment of
      the high degree of organization of this voyage as far as food supplies and
      medical support are concerned, but it also shows the reflection and the diagnosis
      correction of tuberculosis of the lungs, in a seaman, carried out by a surgeon on
      board, which we totally refute. The latter, which only aims at giving some
      further data for the study of the Portuguese Diplomatic History, let us know some
      of the complex procedures and protocols established between our diplomatic
      representative and the high Chinese rulers, both the Emperor himself and the
      mandarins. Contrary to other previous attempts of diplomatic, economic and social
      relations, either partially or totally frustrated, this mission constituted a
      great success for Portugal and may, indeed, be considered as a decisive step for
      the recognition of Portuguese sovereignty over the territory of Macao and its
      dependencies in 1887.

PMID- 7717108
TI  - [Medical responsibility in hospital emergency services].
AB  - Questions of medical responsibility of doctors working at the emergency services
      of the public hospitals have been increasing during recent years in Portugal.
      Several reasons may be contributing to the present situation and some of them are
      analysed: the organization of the service, the triage, the team work and the co
      responsibilization of the hospital administration. The sharing of the
      responsibility among these several entities is discussed within the framework of
      the Portuguese bylaws regarding the responsibility in general and that of the
      doctors in particular.

PMID- 7717109
TI  - [Quality control of vagotomy in duodenal ulcer perforation].
AB  - The efficacy of truncal vagotomy combined with pyloroplasty has been studied in
      56 patients, divided into the following groups: Group I-29 patients submitted to
      bilateral truncal vagotomy (BTV) and pyloroplasty, as the method of treatment to
      solve the problem of perforated duodenal ulcer (initial and retrospective phase
      of study). Group II-With 11 patients, who underwent the same operation as those
      in Group I but with the surgeon's knowledge of the results of phase I and also
      awareness of the laboratory control of its surgery (prospective phase). Group III
      A control Group of 16 patients, with chronic duodenal ulcer submitted to a
      routine proximal gastric vagotomy (superselective or hyperselective vagotomy).
      All of the patients were clinically evaluated and all of them have done acid
      secretion studies (Kay and Sham-Feeding test). Basal acid output (BAO), maximum
      acid output after Sham-Feeding (PAOsf), and pentagastrine (PAOpg), were
      determined in order to control the efficacy of vagotomy. In group III, results
      were compared with those obtained pre-operatively. In Group I, 48.27% of patients
      had a PAOsf higher than 4 mEq/hour-value which has been considered the maximum
      level of normality after complete BTV without gastric resection. In Group II, the
      number of patients with incomplete vagotomy decrease to 18.18%. In Group III, all
      the patients had a PAOsf lower than 4 mEq/hour and 83.81% of acidity reduction
      after Sham-Feeding test, in comparision with the pre-operative values.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7717110
TI  - [Maternal anthropometric characteristics. Risk of intrauterine growth
      retardation].
AB  - The aim of this study was to evaluate the association between maternal
      nutritional factors and intrauterine growth retardation (IUGR). We studied 1233
      mothers who delivered single term newborns: 144 IUGR-birth weight less than one
      10th percentile for sex and gestational age and 1119 controls-birth weight
      between the 10th and the 90th percentile. Maternal anthropometric factors
      (height, weight before and at the end of pregnancy, total and weekly weight gain
      and body mass index) were stratified according to quartiles of distribution in
      the studied population. Unconditional multiple logistic regression was used to
      estimate odds ratios (OR), adjusting each anthropometric parameter for non
      nutritional confounders (parity, smoking, gestational illness and history of low
      birth weight) and the effect of prepregnancy weight or weight gain. Mothers of
      IUGR cases showed significantly lower mean values of pre and end pregnancy
      weight, body mass index and total or weekly weight gain. Compared to the
      reference category (first quartile) women in upper quartiles of total or weekly
      weight gain, or end pregnancy weight showed significantly lower risks. For a
      total weight gain of 10-11 kg an OR of 0.43 was found, and that for a weekly gain
      of 238-297 g was 0.35. An end pregnancy weight between 63 and 68 kg had an OR or
      0.45. However, compared to the second no evident benefit was found for the third
      or fourth quartiles of weight gains, where an increased risk of macrosomia can be
      anticipated. These results indicate that attitudes during prenatal care towards
      adequate weight gains may further reduce the risk of IUGR and the associated
      morbidity and mortality.

PMID- 7717111
TI  - [Fecal incontinence. What to do?].
AB  - There are various functional or organic pathologies that can interfere with the
      defecation mechanism. The authors present 4 clinical cases with fecal
      incontinence: 1 false enconprese--2 myelomeningoceles--1 ileo-anal anastomose
      (total colectomy in Behcet disease). All cases were evaluated manometrically and
      operated with myorrhaphy of the rectum levators, plasty of gluteus muscles with
      approximation and median suture, (without rectum circumferential dissection),
      associating contiguous muscles of independent enervation. In incontinence due to
      ileo-anal anastomose, a prior ileostomy was made and an S ileal anal-pouch
      reconstructed. In other cases any intestinal derivation was made. In 3 cases,
      post operation treatment went well without incidents and there was a clear
      improvement in the continence. In the other case (myelomeningocele) a
      complication developed-an abscess with suture dehiscence-which most likely
      contributed to a less satisfactory result. After the incontinence cases being
      entirely studied the technique followed is easy to use, adopting neighboring
      muscular groups capable of improving the continence mechanism.

PMID- 7717112
TI  - [Prevention of dental caries. Risk groups].
AB  - The identification of the risk groups, in what concerns dental caries, is
      difficult because the etiology of the disease is multifactorial. Some indicators
      were selected to overcome these difficulties. Once the risk groups are known, the
      principle precautions of the prevention strategy are established.

PMID- 7717113
TI  - [Gastric tuberculosis].
AB  - A 37 year old woman with duodenal ulcer not responsive to medical treatment was
      operated. Antrectomy, truncal vagotomy and Bilroth II gastrojejunostomy were
      performed. The histopathology revealed epithelioid cell granulomas with
      multinucleated cells and central ceseation, in the gastric side of the pylorus
      and in three isolated lymph nodes. With Ziehl-Neelsen staining there were
      multiple acid-fast bacilli. There was no evidence or previous history, personal
      or familial, or tuberculosis in an other localization. Epidemiology, pathology,
      diagnosis, and treatment of gastric tuberculosis are discussed according to the
      literature.

PMID- 7717114
TI  - [Portal hypertension. Report of a case with a long-term course].
AB  - The AA report a clinical case of Portal Hypertension with a long period of
      survival, more than 12 years, during which it was not possible to clarify the
      etiology. The presence of chronic ethylism conditioned the attribution of the
      etiology to a chronic alcoholic hepatopathy, but a hepatic biopsy denied that
      cause. Through the re-examination of the differential diagnosis of the several
      causes of Portal Hypertension and through Echographic findings, the Budd-Chiari
      Syndrome diagnosis was established. The AA broach the causes, the means of
      diagnosis and the therapeutics of this syndrome and conclude that the etiological
      diagnosis of any Portal Hypertension must be done exhaustively, using all the
      available means, so that effective therapeutics can be achieved.

PMID- 7717115
TI  - [Inflammatory pseudo tumor of the bladder (in a 6-month-old girl)].
AB  - We describe the clinical case of a six-month old female child, who presented an
      intra-vesical mass as a sequence of urinary tract infection. After surgical
      resection the histopathological study was consistent with the diagnosis of
      inflammatory pseudotumor of the bladder.

PMID- 7717116
TI  - [Angiosarcoma of the spleen].
AB  - Primitive splenic tumors are extremely rare. We report a case, the first at S.
      Jose-Hospitais Civis de Lisboa, of a 70 year old woman who presented
      splenomegaly. She had pelvic irradiation in her past history. MRI revealed a
      splenic mass characterized as vascular on angiography. She is doing well 12
      months after splenectomy. We have found 61 reported cases of this rare tumor
      whose etiopathogeny is unknown. Early splenectomy should be the first
      therapeutical approach, since spontaneous rupture is very common and was the
      feature presented in 34% of patients in the series by Autry et al. As far as
      cytostatic chemotherapy is concerned, the rarity of this tumor precludes any
      conclusion about its efficacy, but in metastasized forms it seems that
      chemotherapy for soft tissue sarcomas may be effective.

PMID- 7717117
TI  - [Pheochromocytoma].
AB  - The authors present the case of a 51 year old woman with severe arterial
      hypertension with parixisms, without medical control. The clinical, laboratory
      and imagiological investigation showed a pheochromocytoma at the right adrenal
      gland. The patient was submitted to surgery with success. Specific aspects of
      differential diagnosis are discussed and a review of the more relevant features
      of clinical diagnosis, pre-operative preparation and surgical technique are
      presented.

PMID- 7717118
TI  - [Stress proteins].
AB  - Cells from all organisms have developed a remarkable number of strategies to deal
      with adverse changes in their environment. One of these protective mechanisms is
      the heat shock response, or stress response, characterized by the extremely rapid
      increased expression of a selected group of proteins--the heat shock proteins
      (hsp)--after a sudden increase in the normal cellular growth temperature. The
      same response takes place when cells are subjected to a wide variety of other
      stressors: a) environmental assaults: exposure to heavy metals, alcohols,
      inhibitors of energy metabolism, amino acid analogues; b) states of disease:
      ischemia, oxidative injury, infectious diseases, immunity disorders and
      malignancy. On the other hand, some hsp are believed to play an important role in
      protein maturation steps and in cellular development and differentiation. The
      understanding of stress response is still incomplete but the promise of its
      medical applications for fighting against ischemia, infection, immunity diseases
      and cancer is clearly on the horizon.

PMID- 7717119
TI  - [Treatment of acute promyelocytic leukemia with trans-retinoic acid. Experience
      of the Santa Maria Hospital, Medical School of Lisbon].
AB  - Acute promyelocytic leukemia (APL) is a rare subtype of acute myelogenous
      leukemia that is usually associated with a fatal hemorrhagic diathesis. All trans
      retinoic acid (ATRA) is an active metabolite of vitamin A that differentiates the
      malignant cell clone, corrects the coagulopathy, and induces complete remission
      in the vast majority of patients with APL. Between June 1992 and September 1993,
      8 patients with APL (4 previously untreated, 3 in first relapse and 1 in second
      relapse) received ATRA. Complete remission was achieved in 7 patients; in 5 with
      ATRA alone and in 2 with ATRA followed by cytotoxic chemotherapy due to the
      development of asymptomatic hyperleukocytosis. The earliest signs of response
      were the correction of the coagulopathy and an increase in the white blood cell
      count. Sequential morphological and immunophenotypical analyses of the bone
      marrow revealed differentiation of the malignant cell clone, in the absence of
      bone marrow hypoplasia. 4 of 5 patients treated only with ATRA until complete
      remission had late leukopenia. The most frequent adverse effects were dryness of
      skin and mucosae, hypertrigliceridemia and hypercholesterolemia, and a moderate
      increase in liver transaminases. An increase in the white blood cell count was
      common, and in two cases exceeded 35.0 x 10(9)/l. One of these patients developed
      multiple thrombosis of the extremities after cytotoxic chemotherapy. We
      frequently observed an increase in lactic dehydrogenase levels that was
      concomitant with the peak in the white blood cell count. The only patient on whom
      complete remission was not achieved was 60 years old, had chronic obstructive
      pulmonary disease, and died in the third week of therapy with a pulmonary
      distress syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717121
TI  - Proceedings of the 1st Congress of the International Stereotactic Radiosurgery
      Society. Stockholm, June 1993.

PMID- 7717120
TI  - [Ultrasonographic diagnosis of disease of the rotator cuff and the subacromial
      bursa: criteria].

PMID- 7717122
TI  - Lars Leksell's vision--radiosurgery.

PMID- 7717123
TI  - Radiosurgery of carotid-cavernous fistulae.
AB  - 25 cases of carotid-cavernous fistulae (CCF) who underwent radiosurgery with a
      conventional gamma source from 1977 to 1992 are reported. 22 were low-flow,
      spontaneous CCFs and 3 were high flow fistulae which had undergone a previous
      trapping. The total dose delivered was 30 to 40 Gy. 91% to patients with low-flow
      CCF cured after radiosurgery in a mean time of 7.5 months, presenting improvement
      in a mean time of 2.3 months. Only one of the high-flow fistulae was cured.
      Follow-up period ranged between 14 years and 15 months (mean: 50 months). No
      recurrence was recorded in any case. While intravascular embolotherapy is the
      treatment of choice for high-flow fistulae, stereotactic radiosurgery may be the
      elective treatment for low-flow CCF.

PMID- 7717124
TI  - Quality assurance for non-invasive patient fixation during stereotactic
      convergent beam irradiation.
AB  - Using a non-invasive mask this patient fixation system for stereotactic
      radiotherapy allows one to perform fractionated irradiation. Measuring the
      statistical quantities of patient motion and positioning uncertainties and
      calculating its effect on a spherically symmetric dose distribution showed that
      there is no severe disadvantage in most cases. Only if small field-size,
      excentric target volume localisation and extreme proximity to an organ at risk
      coincides have the statistical effects to be taken into account. The greatest
      measured standard deviation for positioning uncertainty was 2.3 mm. Its effect on
      the dose distribution with a field size of 9.1 mm increases the diameter of the
      80% isodose to about 115%.

PMID- 7717125
TI  - Medial thalamotomy with the Leksell Gamma Knife for treatment of chronic pain.
AB  - The authors describe 10 patients who underwent stereotactic medial thalamotomy
      with the Leksell Gamma Knife for treatment of chronic intractable pain. The pain
      was related to structural spinal disorders (4), postherpetic neuralgia (2),
      spinal cord injury (1), thalamic syndrome (1), anesthesia dolorosa of the face
      (1), and brainstem infarction (1). All patients had undergone extensive treatment
      with a variety of modalities prior to gamma thalamotomy. Nine patients underwent
      unilateral and one patient bilateral lesions. Magnetic resonance imaging (MRI)
      was used for target localization and the lesions were directed toward the
      intralaminar nuclei, the lateral portion of the medial dorsal nucleus, the
      centrum medianum and parafascicular nuclei. The lesions were made with radiation
      doses of 160-180 Gy using a 4 mm beam collimator and either a single isocenter (1
      patient) or two isocenters (9 patients). Follow-up MRI scans in all patients
      showed well localized lesions. Three patients experienced excellent pain relief,
      four had good pain relief and three were failures. No complications were seen in
      any of the patients. In the past gamma thalamotomy was used mainly for treatment
      of pain related to malignancies but our results indicate that it may also be a
      safe and effective treatment for pain of nonmalignant origin as well.

PMID- 7717126
TI  - Radiosurgery of epilepsy. Long-term results.
AB  - Based on experimental research, since 1982 until 1991 a series of 11 patients
      diagnosed as suffering from idiopathic focal epilepsy have been treated with
      stereotactic radiosurgery. Focus location was determined with cortical electrodes
      and confirmed by stereotactically placed deep electrodes. Stereotactic
      radiosurgery was performed with photons from a cobalt source with a dose of 10 to
      20 Gy, except in two cases in whom a betatron was used. The results were:
      complete cessation of seizures in four cases and a significant reduction in the
      number of seizures in five additional cases. Seizures began to decrease gradually
      after a period of three months of one year, except in two cases in whom there was
      an immediate response after treatment. In two cases there was no change. No
      complication related to the irradiation was recorded. The gradual and delayed
      effect, obtained with low doses, may favour the hypothesis that non-descructive
      permanent structural changes, possibly related to the neuronal plasticity
      phenomenon, constitute the mechanism underlying these facts. Although the number
      of cases so far is too small, the absence of side-effects may make this bloodless
      method the one of choice specially in those cases in whom eloquent areas are
      involved.

PMID- 7717127
TI  - Application of stereotactic radiosurgery to the head and neck region.
AB  - Nasopharyngeal carcinoma recurrent following primary radiation therapy has been
      treated with surgery and reirradiation. Reirradiation is often limited by the
      tolerance of structures previously treated. Radiosurgery was used to boost the
      recurrent site while avoiding critical structures. Seven patients were evaluated
      for treatment. Three patients met requirements for treatment. The lesions invaded
      the parapharyngeal region, the base of skull, cavernous sinus, cranial nerves, or
      carotid artery. Treatment included a radiosurgery boost utilizing multiple
      isocenters, noncoplanar arcs, and arc weighting, to yield a plan conforming to
      the tumors while avoiding critical anatomical structures. The patients tolerated
      the procedure well with minor acute side effects. Follow-up included magnetic
      resonance imaging (MRI) and positron emission tomography (PET). Two lesions
      responded, and one had no significant change. One patient had a regional
      recurrence. Two patients had distance recurrence. Long term side effects include
      trismus, parotiditis, ear fullness, hemorrhage, and pain. Radiosurgery may
      improve the local control rate of such lesions, however, with the severe long
      term complications of single fraction radiosurgery in the head and neck region
      this procedure may be more beneficial if the treatment is fractionated.

PMID- 7717128
TI  - Stereotactic radiotherapy: a technique for dose optimization and escalation for
      intracranial tumors.
AB  - Stereotactic radiosurgery offers the ability to treat relatively small volume
      intracranial lesions with single fraction, high dose radiotherapy while sparing
      surrounding tissue due to rapid fall off of dose outside of the treatment volume.
      Conventional radiotherapy takes advantage of the sparing effects of dose
      fractionation, but includes relatively large amounts of normal brain in the
      treatment volume the tolerance of which is dose-limiting. For some intracranial
      lesions it may not be optimal to treat with large single fractions due to tumor
      location or size. Conventional fractionated radiotherapy may not be optimum in
      all cases due to the necessary inclusion of normal structures. Through the
      development of relocatable head frames, the precision of stereotactic techniques
      and the biologic advantages of fractionation may be combined in stereotactic
      radiotherapy (SRT). We report on the treatment of 68 patients with intracranial
      lesions using a dedicated stereotactic linear accelerator to deliver SRT between
      June 1992 and June 1993. SRT was used either in order to optimize dose
      distribution and spare normal tissues in patients with excellent prognosis or in
      order to increase the dose to tumor while keeping doses to normal tissues below
      tolerance levels in patients with poorer prognosis (dose escalation). Histologies
      treated included meningioma, low grade astrocytoma, pituitary adenoma and
      acoustic neuroma. The most common treatment sites were the parasellar region and
      cavernous sinuses. Most patients (79%) had surgical debulking prior to SRT. 10-12
      patients were treated daily. Patient positioning using relocatable stereotactic
      frames was highly precise. Acute and subacute side effects were minimal and
      radiographic responses have been similar to those expected with conventional
      radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717129
TI  - Radiosurgery dose distributions: theoretical impact of inhomogeneities on lesion
      control.
AB  - OBJECTIVE: To develop a mathematical model to predict the impact of dose
      heterogeneities on tumor/lesion control during radiosurgery. It is necessary to
      be able to estimate these effects in order to quantitatively and objectively
      assess competing treatment plans. METHODS: Target cells are assumed to be
      uniformly distributed throughout the lesion. The control rate for the entire
      lesion is assumed to be the product of the control probabilities for each
      subregion within the target volume. The lesion control probability (LCP) for each
      region is assumed to equal EXP (the number of surviving target cells within the
      subregion), as predicted by Poisson statistics. Subregions of variable size are
      assumed to receive variable doses, and the impact of this dose heterogeneity on
      the LCP is calculated based on the single-fraction radiation cell survival curve
      predicted by the single-hit multitarget model. RESULTS: The impact of a dose
      heterogeneity on LCP is related to three variables: the LCP predicted with
      uniform irradiation, the volume of the lesion that is irradiated to a new dose,
      and the magnitude of the dose change relative to the slope of the single-fraction
      radiation cell survival curve of (delta D/Dzero). The calculations predict that
      the detrimental effect of underdosing regions of the lesion can, in some
      instances, be offset by escalating the dose to other subregions within the target
      volume. In this regard, the "average" dose delivered to the lesion rather than
      the minimum dose may be most predictive of the lesion control probability. In
      some situations, escalating the dose to part of the lesion may improve the lesion
      control rate. CONCLUSION: These calculations quantify the theoretical impact of
      dose heterogeneities on lesion control rate and may be very useful when comparing
      competing treatment plans.

PMID- 7717130
TI  - Intrinsic and extrinsic characteristics of human tumors relevant to radiosurgery:
      comparative cellular radiosensitivity and hypoxic percentages.
AB  - We have collected the in vitro x-ray radiation survival characteristics of 181
      lines from 12 different classes of exponentially growing human tumor cells
      (sarcomas, lung cancers, colo-rectal cancers, medulloblastomas, melanoma, breast
      cancers, prostate cancers, renal cell cancers, grades III and IV brain tumors,
      ovarian, and head and neck cancers). This information was used to intercompare
      survival after single high doses of 20-40 Gy for each tumor line.
      Radiosensitivities could roughly be divided into two groups. The more
      radiosensitive group included: sarcoma, small-cell lung cancer, non-small cell
      lung cancer, colorectal cancer, medulloblastoma and melanoma. The more
      radioresistant group included breast, prostate, renal cell, primary brain tumors,
      ovarian tumors, and head and neck cancers. Using a model of a 3 cm diameter brain
      lesion containing about 1.4 x 10(9) oxic cells, the single doses calculated to
      reduce survival to 1 cell were: sarcoma and small cell lung cancers-22-23 Gy;
      melanoma-25 Gy; non-small cell lung and colorectal cancer-26 Gy; medullo-blastoma
      28 Gy; breast, prostate, renal cell, primary brain tumors, ovarian tumors, and
      head and neck cancers-30-36 Gy. If, however, tumors contained on average 20
      percent hypoxic cells, the dose needed for equivalent cell killing increased by
      about a factor of 2.6-2.8. Also, there was no correlation between the ranking of
      relative radiosensitivities of the various classes of tumor cells at high doses
      (as in radiosurgery) to the sensitivity at low doses (as in conventional
      fractionated radiotherapy). CONCLUSION: available information on the intrinsic
      radiosensitivity of human tumor cells indicates that meaningful differences exist
      among different histological classes of neoplasm that are relevant to the single
      high doses used in radioneurosurgery, and which could constitute a basis for
      "tailoring" the administered dose to the particular neoplasm. However, if
      intracerebral lesions contain a large number of hypoxic cells (e.g., 20%), this
      may constitute a significant problem.

PMID- 7717131
TI  - A universal, multi-modality localization system for animal radiosurgery.
AB  - We have developed a stereotactic localization system allowing a radiosurgical
      approach in a number of animal models. The system utilizes fixation adapters
      specially designed for a particular animal, which in turn are attached to a
      common Brown-Roberts-Wells (BRW) compatible Delrin head ring. Each fixation
      adapter is constructed using materials compatible with CT, MRI, PET, and
      angiographic imaging studies. With such a system, radiographic localization,
      computerized treatment planning, and stereotactic radiation delivery can
      subsequently be performed in a manner identical to the procedures used for
      humans.

PMID- 7717132
TI  - Stereotactic radiosurgery for pituitary adenomas: imaging, visual and endocrine
      results.
AB  - To determine the endocrine, ophthalmologic, and tumor growth control responses
      after stereotactic radiosurgery using the gamma unit, we reviewed our experience
      in 35 patients with pituitary adenomas. Twenty-four females and 11 males (mean
      age 47 years, range 9-81 years) had radiosurgery with average follow-up of 26
      months (range 6-60 months). Most patients were refractory to surgical removal.
      Fifteen patients had Cushing's disease. Prior transsphenoidal resection was
      performed in 14 patients (6 had two prior operations), fractionated radiotherapy
      in 3, and adrenalectomy in 2. In 11 evaluable patients, the hormone response was
      normalized in 8, decreased in 2 and increased in 1. Five patients remained on
      cortisol suppression. Of 12 patients with imaging follow-up, 4 had decreased
      tumor size, 6 had no change, and 2 had an increase; these 2 patients underwent
      subsequent surgery. Ten patients had acromegaly, and 6 had undergone prior
      surgery. Of 8 evaluable patients, growth hormone secretion has normalized in 3,
      decreased in 3, and increased in 2. Six tumors decreased in size, and 2 were
      unchanged. One patient had repeat resection 21 months after radiosurgery and one
      patient underwent repeat radiosurgery. Ten patients had non-secreting adenomas;
      all 10 had prior operations (1-4 operations, 6 underwent frontal craniotomy) and
      5 had undergone fractionated radiotherapy. Eight patients had panhypopituitarism
      prior to radiosurgery. Four tumors decreased in size and 6 were without
      change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717133
TI  - Tumour volume reduction following gamma knife radiosurgery: the relationship
      between X-ray and histological findings.
AB  - The case histories of two young ladies with Cushing's disease are described. Both
      patients were treated first with Gamma Knife radiosurgery and subsequently by
      microsurgery. The radiosurgery caused a marked reduction in tumour volume but
      only a partial relief of the endocrinopathy. Comparison of the histological
      findings with the radiological findings following radiosurgery indicates that
      confluent necrosis is not a prerequisite for a reduction in tumour volume. It
      seems more likely that the reduction in tumour volume is related to changes in
      cellular dynamics.

PMID- 7717134
TI  - Radiosensitive craniopharyngiomas: the role of radiosurgery.
AB  - Clinical characteristics of radiosensitive craniopharyngiomas and histologically
      identical tumours were re-evaluated from among 53 patients. There were 9 squamous
      cell type and 3 mixed type tumours. Early effects of radiosurgery for two recent
      cases are reported. Radiosurgery may have an important role to play in the
      treatment of craniopharyngiomas, especially of the squamous cell type.

PMID- 7717135
TI  - A comparison of survival between radiosurgery and stereotactic implants for
      malignant astrocytomas.
AB  - The purpose of this paper is to compare the survival of three groups of patients
      with high grade supratentorial gliomas who were treated on three sequential
      protocols with surgical resection, external beam fractionated radiotherapy and a
      boost to the residual contrasting enhancing mass by either interstitial
      brachytherapy (IB, n = 33), by interstitial thermoradiotherapy (IT, n = 25) or by
      stereotactic radiosurgery (SRS, n = 19). The primary aim of this study was to
      evaluate the role of different boosting techniques in the initial management of
      primary brain tumors. External beam radiotherapy doses were escalated from one
      study to the next so that the median doses given to the IB, the IT, and the SRS
      groups were 41.4 Gy, 48.4 Gy, and 59.4 Gy, respectively. The median dose of
      interstitial irradiation or stereotactic radiosurgery, were 40 Gy, 32.2 Gy and 10
      Gy, respectively, for the same groups. Follow-up was such that all living
      patients had been followed for a minimum of 30, 27, 4 months in the IB, IT, and
      SRS groups, respectively; hence, twelve-month survival was 52% (95% CI: 34%-69%),
      80% (95% CI: 64%-96%), and 51% (95% CI: 24%-78%) in the same respective groups.
      Using a multivariate Cox proportional hazards model, treatment with IT conferred
      a survival advantage over IB (p = 0.029). Furthermore, survival of patients
      treated with SRS did not significantly differ from that of patients treated with
      an implant with or without hyperthermia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717136
TI  - Linear accelerator radiosurgery of cerebral arteriovenous malformations: current
      status.
AB  - 228 patients affected by cerebral arteriovenous malformations (AVMs) underwent
      linear accelerator radiosurgery. Follow-up ranges from 1 to 100 months (mean 42
      months). Complete angiographic obliteration was achieved in 47% of treated
      patients at one year and 80% at 2 years. 17 haemorrhages were observed after
      treatment and 6 patients died from them. No bleeding took place after complete
      angiographic obliteration. 11 patients suffered for radionecrosis. In 6 patients
      complete recovery was obtained with corticoid medication. The aim of this study
      is to present our results and to evaluate the effect of irradiation on the risk
      of bleeding after radiosurgery. Patients were considered at risk in the time
      lapse after irradiation and before angiographic obliteration or other definitive
      treatment or death. Patients were followed from the date of radiosurgery and the
      number of haemorrhages were recorded every six months. In our series the bleeding
      risk in patients harbouring incompletely obliterated AVMs decreases from 8% in
      the first year after radiosurgery to 0% starting from the 24th month of the
      follow-up.

PMID- 7717137
TI  - Stereotactic radiosurgery for tectal low-grade gliomas.
AB  - We report 7 cases with low-grade gliomas in the tectal region of the midbrain.
      This series started in 1979 and all tumors were treated by radiosurgery using the
      Leksell Gamma Knife. All cases were treated by using a single isocenter with the
      14 mm collimator. Doses administered ranged from 14 to 35 Gy delivered to the 50
      70% isodose line. All tumours but one responded to the treatment and disappeared
      or ceased growing. In the first two treated cases, the dose was chosen by the
      early experience from the AVM's, with 30 and 35 Gy as the peripheral dose. These
      cases developed severe radio-induced oedema with aggravating symptoms and
      permanent deficits. We conclude that radiosurgery is effective in the treatment
      of deeply located low-grade gliomas. Cases accepted for treatment should be
      carefully selected and the peripheral dose should not exceed 14Gy to avoid
      uncontrolled radio-induced changes.

PMID- 7717138
TI  - Stereotactic radiosurgery of deeply seated low grade gliomas.
AB  - The authors report the results of a series of 16 cases of low-grade gliomas in
      whom radiosurgery was performed. This series started in 1977. All the tumours
      received a single radiosurgical session (with a mean dose of 21.7 Gy, 5-10 mm.
      collimator; one patient received two sessions and in another patient two
      different targets were irradiated in the same session). Prior to radiosurgery,
      six patients received conventional external fractionated radiotherapy, with two
      lateral fields of up to 10 x 10 cm. and a mean dose of 55.1 Gy and another six
      patients with tumours less than 5 cm. in diameter, received stereotactic
      radiotherapy using four fields of up to 5 x 5 cm. and a mean dose of 53.1 Gy. In
      both cases, conventional fractionation was used, giving a dose of 1.8 to 2
      Gy/day. The tumour disappeared in 8 cases (50%) and shunk or ceased its growth in
      5 additional cases (31%). In 3 cases of brainstem gliomas in which the clinical
      condition was previously very poor there was no evolutional change and the
      patients eventually died. We conclude that radiosurgery is effective in the
      treatment of deeply seated low-grade gliomas, where it may become the treatment
      of choice in the absence of other more definitive choices.

PMID- 7717139
TI  - Radiosurgical treatment of gliomas of the diencephalon.
AB  - The results of Leksell Gamma Knife treatment of diencephalic gliomas are
      presented. Eight tumours in seven patients form the basis of this report. 7
      patients, 4 males and 3 females. The age range was 7.5 to 33 years with a mean of
      18 years. Mean follow-up was 21 +/- 12 months. In 4 patients the tumour had been
      reduced in volume by an open internal decompression procedure. The location of
      the tumour will determine the risks of treatment. With anterior lesions there is
      risk of endocrinological and visual pathway damage. With a pineal region lesion
      there is a risk of diplopia. In this series no tumour has increased in volume.
      Four have decreased and one has disappeared. Two patients suffered temporary
      diplopia. No visual disturbance has been observed to date. No hypothalamic
      disturbance has been observed yet. These tumours are dangerous not so much
      because of their biological nature as because of their location. However, the
      biological nature of the tumours, with the close concordance between the
      radiological and actual extent make them appropriate targets for radiosurgery as
      a primary treatment. The present study gives preliminary support to this line of
      treatment.

PMID- 7717140
TI  - Long-term follow-up of gliomas treated with fractionated stereotactic
      irradiation.
AB  - Eighteen patients have been treated for gliomas with fractionated stereotactic
      linear accelerator (LINAC) irradiation. A plastic halo ring secured with skull
      pins allows daily attachment of the patient to the stereotactic frame mounted on
      the linear accelerator. The patients received 9-31 fractions of 1.8-3 Gy/fraction
      over periods of 20-49 days. Total doses delivered stereotactically where 16-60 Gy
      (90% isodose) delivered to 3-7 cm diameter tumors. The six patients with
      glioblastoma had a median survival of 16 months (range 7-60 months). The two
      patients with anaplastic astrocytoma survived 7 and 78 months. Most of the
      patients with high grade tumors also received other adjuant treatments. Of the
      ten patients with low grade gliomas, one expired 66 months after treatment, and
      the remainder are alive 22-82 months after treatment. One pediatric patient
      displayed evidence of focal radiation injury with visual loss. No patient
      developed initial recurrence of tumor outside the focally irradiated field.
      Stereotactic localization of irradiation protects surrounding brain tissue;
      fractionation improves the therapeutic ratio. These extended follow-up data
      indicate that stereotactic restriction of radiation fields in treatment of
      gliomas does not result in deterioration of survival results. Further
      investigation is warranted into the use of higher focal fractionated radiation
      doses to attempt to improve local control and survival.

PMID- 7717141
TI  - Linac radiosurgery in brain metastases.
AB  - Brain metastases are usually well-circumscribed and more or less spherical
      lesions. These conditions meet the criteria for radiosurgery (RS). A pilot study
      initiated by our group in 1983, demonstrated the effectiveness of Linac-RS in the
      treatment of solitary brain metastases with low radiosensitivity. A second trial
      including patients with 1-3 metastases started in 1990. By April 1993, 46
      patients had been treated in this series. The radiation doses delivered to the
      tumour margin ranged from 10 to 25 Gy, and were chosen with respect to size,
      number and location of the tumours or previous whole brain radiotherapy (WBRT),
      decreasing mainly with increasing tumour volumes. 34/46 patients had a follow-up
      of more than 12 weeks. In 7/46 patients the disease progressed rapidly during the
      first weeks after RS and follow-up examinations were not performed. 5/46 patients
      had a follow-up of less than 6 weeks and follow-up CT/MR-examinations were not
      available. 14/46 patients received WBRT before RS. The regularly performed follow
      up examinations (clinical status, CT-/MR-examinations in 6 or 12 weekly
      intervals) revealed tumour progression in 5/34 patients. Permanent cessation of
      the growth (11/34), tumour shrinkage (18/34) and decrease of surrounding oedema
      together with clinical amelioration have been observed a few weeks after
      radiosurgery. The median follow-up was 50 weeks. 14/46 patients died due to
      generalized progression of their disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717142
TI  - Gamma knife radiosurgery of a series of only minimally selected metastatic brain
      tumours.
AB  - From December 1991 to October 1992, 77 lesions in 25 consecutive patients were
      treated with Gamma Knife radiosurgery. Thirteen patients (52%) had multiple
      metastases up to sixteen lesions and twelve patients had a single metastasis. The
      volume of the largest tumour treated was 12.5 cm3. Karnofsky performance status
      (KPS) of the patients was 20-90% (mean 70). Marginal tumour dose given was 18 to
      35 Gy (mean 26.1 Gy) in 30 to 90% isodose line according to the tumour volume and
      site. All but two patients were followed by MRI or CT scan repeatedly for a
      minimum of 6 month or to death. All but one of the tumours were locally
      controlled. Seventeen patients died during follow up and in four death was due to
      remote CNS metastases. The median survival for this minimally selected group of
      patients was 8.5 months, and the median survival for the patients with a single
      metastasis was 10.5 months. In patients with multiple metastases the median
      survival reached only 2.5 months but in 11 patients out of 13 patients
      neurological symptoms and signs improved or stabilized shortly after
      radiosurgery.

PMID- 7717143
TI  - Long-term follow-up study of conventional irradiation for brain tumours in
      children: a role for radiosurgery.
AB  - 21 younger patients (less than 10 years of age) with brain tumours, treated by
      conventional irradiation, were followed 5 to 20 years (mean 12), using CT scan
      and/or MR imaging, in order to evaluate adverse effects on the developing brain.
      Pathological changes such as brain atrophy, lesions in the white matter,
      calcifications in the brain, and angiopathy were observed in 13 (62%) out of 21
      cases. The incidence of abnormalities was related to the age at treatment and the
      follow-up period. All six cases treated at or under 5 years old and followed more
      than 10 years showed pathological changes in the brain. In order to minimize the
      radiation damage, 5 patients with brain tumours less than 5 years old were
      treated by gamma knife surgery. The early results encourage further trials.
      Radiosurgery may play a role as an alternative treatment or as a component of
      future multidisciplinary treatment for brain tumours is children.

PMID- 7717144
TI  - Stereotactic radiosurgery of vestibular schwannomas with a linear accelerator.
AB  - The authors describe their initial experience with stereotactic radiosurgery of
      22 cases with vestibular schwannomas using a linear accelerator. 14 of them with
      a follow-up of at least one year were studied. 6-9 months after treatment 86% had
      central tumour necrosis, 71% tumour shrinkage and none of them evidence of tumour
      growth 3 patients developed reversible facial nerve impairment, 2 had permanent
      facial numbness. Hearing diminished in one case out of three with normal hearing
      and in two out of three with already diminished hearing. Although there is a
      general consensus that microsurgery is the treatment of choice for these benign
      tumours, stereotactic radiosurgery challenges this opinion. Stereotactic
      radiosurgery not only proves to be a valuable alternative for selected cases not
      suitable for microsurgery, but it is conceivable that it will become the
      treatment of choice for small vestibular tumours. Tumour control can be obtained
      in the majority of treated patients with fewer complications and with a higher
      rate of cranial nerve sparing. This series indicates that linear accelerators can
      achieve results similar to the Gamma Unit in the treatment of vestibular
      schwannomas.

PMID- 7717145
TI  - The early effects of gamma knife on 40 cases of acoustic neurinoma.
AB  - Early results of gamma radiosurgery on 44 cases of acoustic neurinoma were
      studied by follow-up MRIs and changes of neurological signs every 3 months. Mean
      follow-up period was 12 (3 to 20) months. Enhanced MRI revealed that the central
      low intensity signal area (LISA) appeared at 3 to 6 months after the treatment,
      which was re-enhanced at 6 to 9 months, then the tumours begun to decrease in
      size at 9 to 12 months, which observation was noted in 11 out of 44 cases (25%).
      The other tumours were unchanged in size. Regarding the side effects, facial
      palsy appeared in 7 cases (16%) after the treatment, of whom 3 cases have
      improved. Trigeminal nerve palsy was found in 3 cases (7%). Deterioration of
      hearing was found in 11 out of 21 cases (52%) who had hearing disturbances before
      treatment. The pathological study of a treated tumour at 11 months revealed that
      central LISA was found as complete necrosis and degeneration of tumour cells and
      vessels with thickening walls found at the margin of the tumour. MRI is not only
      useful for the dose planning of radiosurgery but valuable for the follow-up study
      of treated tumours.

PMID- 7717146
TI  - Quality assurance programme on stereotactic radiosurgery.
AB  - In order to achieve a high level of quality in radiosurgical procedures, a
      quality assurance programme (QAP) has to be worked out. An informal "Quality
      Assurance Task Group" is currently preparing a QAP for that purpose. The concepts
      that have been worked out and critically discussed by the members of the task
      group are presented. The final version of the QAP is expected to be completed at
      the end of 1993.

PMID- 7717147
TI  - [Specialization in psychiatry].

PMID- 7717148
TI  - [Alcohol-related problems in Cantabria].
AB  - It is a cross sectorial epidemiological community survey into a random sample of
      1,816 adult people. The objetivo of our work is to test the existence of some
      social-demographic variables that can be accumulated to the existence of alcohol
      related problems. We found that the men, the young people, with low socioeconomic
      level, and semiurban style of life have the highest risk of alcohol related
      problems. 48% of the sample men have recognized any alcohol related problems
      during the previous year to our study. The highest problem prevalence is
      associated to increased alcohol consumption. After all, there are many people
      with low alcohol consumption who have alcohol related problems.

PMID- 7717149
TI  - [Dysthymia and other depressive disorders: study on personality].
AB  - This work presents the results of an investigation made on a sample of depressive
      patients divided in two groups, one of them made up of dysthymics, another of
      patients diagnosed of any kind of depressive disease (in both cases following the
      ICD-10criteria). To all those patients it was realized the 16-PF personality
      questionnaire by RB Catwell. We analyse and compare one by one, the personality
      traits studied in the proof, specially the untuactions obtained for the patients
      grouping them im "means" and "extremes"; the conclusion is that with more
      frequency that in the rest of depressive patients, in the dysthymic group appear
      extreme values.

PMID- 7717150
TI  - [Nuclear psychopathology in anorexia nervosa].
AB  - Some patients seen for the treatment of an eating disorder do not fulfill
      criteria for either of the two established disorders (Anorexia Nervosa and
      Bulimia Nervosa). This large number of patients currently can only be diagnosed
      as eating disorder not otherwise specified-EDNOS-(in DSM-III-R) or as atypical
      disorder (in ICD-19). The authors study some proposal of definition and
      classification of the Eating Disorders chapter for EDNOS and atypical disorders
      would be far smaller than they are now. Problems associated with the inclusion of
      weight concern as a necessary and defining criterion (the crucial diagnostic
      issue) are reviewed.

PMID- 7717151
TI  - [Migraine and epilepsy: a case report].

PMID- 7717152
TI  - [Psycho-oncology: influence of external perception on the personality
      characteristics in women with cancer].
AB  - Personality traits between two female groups suffering cancer with different
      symptomatology and treatment are compared. The authors study 59 female patients:
      35 with breast cancer and 24 with hematologic neoplasia. The MMPI Inventory and
      the Scale to Measure of Aggression by Ledesma et al were studied. It has been
      found that there are similar personality traits in both groups although there are
      some significant differences. The group with breast cancer showed an increase
      both in the MMPI Si scale (Social introversion) and in self aggression with
      respect to the hematologic neoplasia group. On the other hand, the patients with
      hematologic cancer showed an increase of the hypochondria, depression and
      paranoia as well as hetero aggression.

PMID- 7717153
TI  - [Progress and therapeutic response in the obsessive-compulsive disorder].
AB  - The purpose of the present work was to analyze the outcome of patients diagnosed
      of Obsessive Compulsive Disorder (OCD) after Hospital discharge from our Unit,
      focusing on therapeutical efficacy immediately after discharge and in the follow
      up, searching for good evolution predictors. We have studied 42 patients (26
      females and 16 males) diagnosed of OCD according to ICD-9 diagnostic criteria,
      all patients were hospitalized during a seven years period 1981 and 1988.
      Therapeutical response was evaluated through a (1-4 punctuation) of a Clinical
      Global Impression Scale considering the changes from the moment the patient was
      hospitalized, the day of discharge and in the follow up (mean 4.1 years). 73.8%
      and 71.4% were considered as treatment "responders" the day discharged and in the
      follow up respectively. Through a multiple logistic regression, treatment with
      serotonergic drugs and insidious onset of the illness were identified as short
      term treatment response predictors, while the absence of a previous obsessive
      personality was a long-term therapeutical response predictor. Our results show
      the efficacy of serotonergic drugs and the tact that the presence of a previous
      obsessive personality could have a prognostic value in OCD.

PMID- 7717154
TI  - [Clinical experience with the treatment of metastatic renal cell carcinoma with
      subcutaneous interleukin-2r (IL-2r) and interferon Alpha-2b (IFN Alfa-2b)].
AB  - This work presents our recent clinic experience in the treatment of advanced RCC
      with IL-2 in association to alpha IFN given subcutaneously. Fifteen patient with
      histologically confirmed advanced RCC and measurable lesions were entered in the
      study. Patients were treated in cycles of 7 weeks at a IL-2 dose of 4.8 million
      IU/m2 (induction phase)-2.4 million IU/m2 (maintenance phase) every 12h five days
      a week and alpha IFN: 6 million IU/m2 every 24h three days a week, and were
      afterwards evaluated for response. Responders with localized residual bulk
      underwent rescue surgery. Seven patient has objective response (3 complete, 2
      partial and 2 stable responses). The complete responses were stable and lasted 36
      m, 14 m and 8 m, and global survival was of 14.6 m (3-36 m). All patients had
      toxicity at various degrees but WHO grade II was not exceeded at any time. The
      association of IL-2 and alpha IFN 2b given subcutaneously, appears to have
      antitumoral activity against advanced RCC with durable responses and in a
      proportion similar to other associations in intravenous administration, but with
      lower systemic toxicity. Surgical resection of residual bulk can be beneficial in
      selected patient with partial response.

PMID- 7717155
TI  - [Aponeurotic suspension of the bladder neck as elective treatment of minimal
      stress urinary incontinence in women].
AB  - To correct urine incontinence at minimal exertion in woman, most especially in
      those who have undergone unsuccessful vaginal techniques, we advice the
      aponeurotic suspension of the vesical cervix, with anchorage, in fixed tissue
      (Cooper's ligament or ischiopubic branch) in order to avoid displacement of the
      supporting band and new drops of the vesical cervix, with incontinence relapse in
      the long run. Since 1983 this procedure has been performed in 400 women, with
      various degrees of urinary incontinence on exertion, 140 of whom had previously
      undergone other procedures. Our results have been completely successful in 383
      patient who at year from surgery no longer presented urinary incontinence of any
      degree. These good results lead us to recommend this procedure as the most
      suitable to solve urinary incontinence at minimal exertion, relapses and that
      associated to feeling of urgency in many occasions.

PMID- 7717156
TI  - [Staging error in bladder carcinoma: anatomo-clinical correlation].
AB  - Presentation of clinico-pathological correlation in a series of patients with
      bladder carcinoma. All of them had a complete pathological and clinical staging
      following TNM guidelines (UICC 1987). Clinical evaluation consisted of a clinical
      examination, urography and/or ultrasound, cystoscopy, bimanual palpation under
      anaesthesia and biopsy. As an option, pelvic CAT, MRI and a bone scan were
      performed. In all cases a reliable pathological staging was obtained, either from
      cystectomy or complete TUR. Overall, there is a 66% clinico-pathological
      correlation (60% for Ta category, 78% for T1, 25% for T2, 57% for T3, and 74% for
      T4). There is a global error of 34% (40% of cases clinically considered Ta were
      invasive, 16% T1 were pT2 or more, 42% T2 were pT3 or more, and 10% T3 were pT4;
      while 6% of those considered T1 were pTa, 33% of T2 were pTa or pT1, 33% of T3
      were pT2 or less, and 26% of T4 were pT3 or less). We therefore conclude that
      when T is lower the risk of being clinically understaged is greater, while higher
      T values increase the risk of clinical overstaging. From a practical point of
      view, the most severe errors are in the understaging of T2 and T3 (pT3-pT4)
      tumours and the overstaging of T2 (pT1) tumours. When cystectomy is performed,
      the risk of understaging is greater for tumours interpreted as T2-T3 while the
      risk of overstaging T4 tumours is lower. We conclude that, even when adequate
      staging of bladder cancer is attempted, pre-treatment tumour classification using
      the diagnostic methods currently available is far from satisfactory.

PMID- 7717157
TI  - [Paratesticular neoplasms of mesenchymatous origin. Clinico-pathologic study].
AB  - There is a group of malignant intrascrotal tumours which represent a very small
      number when compared to testicular neoplasias and which are known as
      paratesticular neoplasias. More than 90% belong to the sarcomatous species. From
      a clinical point of view and based on the patient's age, two groups can be
      distinguished: sarcomas affecting children and adolescents (primarily
      rabdomiosarcomas) and those occurring in adulthood, the more frequent
      histopathological variants being fibrosarcoma, leiomiosarcoma and liposarcoma.
      This work contributes five paratesticular sarcomas (two rabdomiosarcomas, one
      liposarcoma, one leiomiosarcoma and one fibrosarcoma). The features related to
      histogenesis, diagnosis (revealing signs and clinical examination), natural
      history (dissemination routes based on histopathology) and treatment are
      reported. With regard to treatment, both the local surgery (total orchiectomy by
      inguinoscrotal approach with or without hemiscrotectomy), and indications for
      lymphadenectomy and radiotherapy in relation to staging are discussed though
      insisting on the chemotherapy approach.

PMID- 7717159
TI  - [Actas Urologicas Espanolas].

PMID- 7717158
TI  - [Wilm's tumor: review and up-date based on our experience].
AB  - Wilms' tumour represents 8% of tumours appearing during childhood, and it is the
      more frequent malignant tumour of the urinary tract in children. A review of 7
      tumours occurring in our Hospital Area over the last 11 years is made, evaluating
      their incidence, clinical presentation, diagnosis as well as therapeutical
      approaches and complications. We also conducted a review of the most recent
      related literature, paying special attention to the new lines of research in the
      field of the genetics. Likewise, we contribute the latest guidelines and
      suggestions by the NWTS with regard to diagnosis and treatment of Wilms' tumour.

PMID- 7717160
TI  - [Tumor of the testicular vitelline sac in children: clinical course and
      treatment].
AB  - Presentation of a review of 10 paediatric patients with tumour of the testis
      vitelline sack, to report our experience in the management of this pathology.
      Mean age was 20 months (14-32), and the interval of the study was from 1970 to
      1994. After orchiectomy, 7 children were included in stage I, 1 in stage II, and
      2 in stage III. Four underwent Retroperitoneal Lymphadenectomy. All patients in
      stage I are currently free of disease, with a mean follow-up of 132 months,
      regardless the type of treatment employed (vigilance in 2 cases, chemotherapy in
      2, and chemotherapy plus Retroperitoneal Lymphadenectomy in 3). On the contrary,
      the 3 children with extratesticular disease died 15, 18 and 15 months after
      orchiectomy. In conclusion, we believe that patients included in stage I should
      undergo only a strict vigilance, based on the excellent prognosis of this group
      and the lack of differences between the survival time obtained with the various
      therapeutical approaches followed. On the other hand, patients with stage II or
      stage III disease should receive from the beginning chemotherapy, thus saving the
      Retroperitoneal Lymphadenectomy for the residual disease.

PMID- 7717161
TI  - [Polypoid cystitis mimicking bladder tumor].
AB  - Presentation of one case of polypoid cystitis in a 38 year-old male, with no
      urological history. The form of clinic presentation and the endoscopic
      exploration induced to suspect the existence of a bladder tumour. Diagnosis was
      confirmed by the result of the histopathological study of the piece.

PMID- 7717162
TI  - [Urinary retention caused by vulvar carcinoma].
AB  - Epidermoid carcinoma is the most frequent neoplasia of the vulva. It usually
      appears in aged post-menopausal women (51-70 years). The signs and symptoms are
      unremarkable: vulvar bulk or protuberance, pruritus, painful ulcer, flow, vulvar
      irritation, dysuria or haemorrhage, all of which motivate that this condition may
      be ignored, overlooked, or be the cause of self-treatment. At other times a
      dangerous shyness causes considerable delays by postponing the visit to the
      specialist. Many patients refuse to go to see a physician. The existence of
      urinary signs and symptoms in a patient with vulvar neoplasia are indicative of
      urethral invasion and the advanced stage of the condition. A case is presented
      here of an advanced vulva carcinoma in an 82 year-old woman who come with urinary
      retention by urethral infiltration and perineal destruction. We review the most
      relevant aspects of vulvar carcinomas associated with obstructive uropathy.

PMID- 7717163
TI  - [Testicular metastasis in prostatic carcinoma].
AB  - Even though prostate carcinomas are the ones which more frequently metastasize
      the testis, this has only happen in 0.12% of our series, representing 0.9% of
      testicular tumours in our centre. Revision of such an uncommon pathology shows
      that in most instances they are asymptomatic, and that the likely route for
      dissemination is lymphatic, therefore they are not necessarily associated to
      visceral metastasis, while their repercussion in the prognosis is limited.

PMID- 7717164
TI  - [Pseudosarcomatous tumor of the bladder].
AB  - Pseudosarcomatous tumour of the bladder is a benign neoforming process of
      uncommon occurrence, consisting in a fibroblastic proliferation originated in the
      vesical wall and the perivesical fat, with unknown etiology, that given its
      cellular pleomorphism and the infiltrative nature of the injury can be
      incorrectly diagnosed as a sarcoma. This paper presents one case of
      pseudosarcomatous tumour of the bladder in a 9 year-old child, with no history of
      local traumatism or previous surgery, consisting in a tumoration affecting the
      vesical wall associated with a significant perivesical fibrosis with extension
      towards the area of the iliac veasels. Microscopically, the injury shows
      proliferation of spindle cells, arranged in a myxoid stroma with a prominent
      vascular net. No cytologic atypia is demonstrated or increase in the number of
      mitosis. The immunohistochemical study shows features of myofibroblasts in the
      proliferant cell. A review of the literature is made on 40 cases of inflammatory
      pseudosarcoma, evaluating the clinical characteristics, morphologic findings and
      treatment involved, as well as the postoperative evolution of the patient.

PMID- 7717165
TI  - [Vascular complications in renal transplantation].
AB  - Between the years 1979 and 1992 we a total of 479 renal transplants (RT) were
      performed. In 62 patients (12.9%) there were some clinically significant vascular
      complications. These have consisted of: 10 cases of arterial thrombosis (2%); 10
      cases of venous thrombosis (2%); 5 cases of arterial and venous thrombosis (1%);
      31 cases of arterial stenosis (6.5%); and 6 cases of acute haemorrhage originated
      at the vascular anastomosis level (1.2%). In all those cases with arterial or
      venous thrombosis, or both, it was necessary to perform transplantation. The
      arterial stenosis cases were treated with antihypertensive agents in 13 patients;
      with endoluminal percutaneous angioplasty (EPA) in other 13 patients and with
      surgery in 5. Both arterial stenosis and complications from their treatment
      resulted in 5 transplantations. In all cases with early post-surgical haemorrhage
      originated at the vascular anastomosis level, a surgical review and suture of
      bleeding site was performed. A total of 31 grafts (6.5%) were lost as a result of
      vascular complications.

PMID- 7717166
TI  - [Postgraduate training in urology].
AB  - Presentation of an updated protocol for training of In-house Urologists.
      Preparation of this protocol was the result of a pilot program undertaken in our
      Hospital by the Teaching Committee. The protocol contemplates in an comprehensive
      way all the activity developed by In-house physicians during their training, at
      the end of which the Teaching Committee prepares a curriculum approved by the
      Urology Tutor and the Consultant. With this a better assessment of the knowledge,
      capacities and attitudes of trained urologists can be obtained.

PMID- 7717167
TI  - Regulation of prostanoid-synthesis in the cardiovascular system.
AB  - Thromboxane A2 and prostacyclin are the two prostanoids involved in the
      regulation of the vascular tone. Their release is controlled by the activity of
      cyclooxygenase which has made this enzyme a preferred pharmacological target. We
      here report on the distribution of the two isoforms of cyclooxygenase in cultured
      mesangial cells and on a selective inhibitor of the cytokine-inducible
      cyclooxygenase-2. We also comment on the structure of thromboxane and
      prostacyclin synthase and their regulation under physiological and
      pathophysiological conditions.

PMID- 7717168
TI  - Molecular regulation and augmentation of prostacyclin biosynthesis.
AB  - Prostacyclin is a major vasoprotective molecule. It has multiple physiological
      functions. Its synthesis is determined by several enzymes of which cyclooxygenase
      (COX) plays a key role. Two isoforms of COX have been identified. Their
      expression and regulation are controlled by different mechanisms. COX-1 is
      constitutively expressed and physiologically important. PGI2 synthesis can be
      augmented by virus-mediated transfer COX-1 gene. This strategy may be useful for
      therapy of vascular thrombosis and tissue ischemia.

PMID- 7717170
TI  - Metabolism and excretion of nitric oxide in man: basal studies and clinical
      applications.

PMID- 7717169
TI  - Kinin-mediated activation of endothelial no formation: possible role during
      myocardial ischemia.
AB  - Endothelial cells produce a variety of factors involved in the control of
      vascular tone, platelet activation and cell growth, one of the most important
      being nitric oxide (NO). Although continuously produced in response to fluid
      shear stress, the release of NO from these cells can be enhanced further by
      humoral stimuli, such as bradykinin. This is the result of a chain of complex
      intracellular events involving changes in Ca2+, pH and protein phosphorylation.
      Endothelial cells are also capable of synthesizing bradykinin from an endogenous
      source, the release of which is markedly enhanced under hypoxic conditions. The
      finding that ACE inhibitors promote the local accumulation of the peptide and
      increase its efficacy at the receptor level may partly explain the potent anti
      ischemic and cardioprotective effects of these drugs.

PMID- 7717171
TI  - Nitric oxide mediates microvascular permeability in the isolated perfused rat
      mesentery?
AB  - The permeability influencing effect of nitric oxide was studied by means of an
      isolated perfused mesentery preparation in combination with a
      intravital/fluorescence microscopic set up. As a fluorescent marker served FITC
      dextran mol wt 70,000 daltons. Tissue treatment was performed by application of
      NO-donors like SNP or GTN. Additionally the effects of bradykinin, L
      nitroarginine or the combination of both were tested in regard to a permeability
      modulation. The results point out that NO-donors did not enhance microvascular
      permeability, whereas the permeability increasing effect of bradykinin is
      mediated by an NO-independent pathway.

PMID- 7717172
TI  - Interplay of nitric oxide and histamine in the regulation of coronary reactive
      hyperemia and coronary autoregulation.
AB  - Reactive hyperemia following 30 s of coronary occlusion in the isolated guinea
      pig heart is accompanied by a two-fold increase of nitric oxide (NO) and
      histamine release, which are significantly reduced in the presence of L-NAME,
      cimetidine and thioperamide, respectively. Great changes of histamine release
      occur during autoregulation. However, histamine seems much more important for
      metabolic dilation below the autoregulatory range. Inhibition of NO synthesis,
      but not blockade of histamine receptors, widens the autoregulatory range. Changes
      of the released NO and histamine under conditions employed in this study suggest
      a positive feed-back relationship between NO and histamine in the regulation of
      coronary circulation.

PMID- 7717173
TI  - Exogenously supplied nitric oxide influences the dilation of the capillary
      microvasculature in vivo.
AB  - An endogenous NO-release which exceeds the basal endogenous NO-release has a
      regulatory effect on capillary microvasculature in isolatedly perfused rat
      hearts. The basal NO-release in contrast has no effect on capillaries. The
      functional findings are corresponding to the endothelial distribution of NOS in
      coronary vessels, which displays a lack of NOS in capillary endothelium. An
      increase of coronary flow by exogenously administered NO-donors does not
      necessarily lead to a dilation of capillary microvasculature. Local differences
      in the release of unstable NO by SNP and GTN are responsible for variations in
      effects. We can conclude: NO influences the dilation of the capillary
      microvasculature independently of flow regulation.

PMID- 7717174
TI  - Effects of prolonged L-arginine administration on blood pressure in patients with
      essential hypertension (EH).
AB  - L-arginine (L-Arg) was administered intravenously through 4 consecutive days to
      20 males (40-63 years old) with essential hypertension (EH). Significant decrease
      (p < 0.02) of systolic blood pressure (SBP) was observed only during the first
      day of the therapy and tachyphylaxis against L-Arg was noticed. The reduction of
      diastolic blood pressure (DBP) was more marked (p < 0.001). Significant changes
      in cGMP plasma level and the nitrite/nitrate urine concentration were not
      observed. L-Arg caused a significant activation of fibrinolysis (p < 0.005). The
      decrease of platelet activity, measured by the ADP-induced aggregation, after L
      Arg administration was not statistically significant. Therefore, L-Arg may play
      only a secondary role in the treatment of EH.

PMID- 7717175
TI  - Elevation of circulating NO: its effects on hemodynamics and vascular smooth
      muscle cell proliferation in rats.
AB  - Object of our study was to characterize the effects of elevated circulating NO on
      hemodynamics and vascular smooth muscle cell proliferation in rats.
      Administration of molsidomine (10, 25, 50 mg/kg, bid p.o.) was followed by
      pharmacodynamic effects: elevation of plasma nitrite/nitrate levels and reduction
      of blood pressure (25 and 50 mg/kg, bid p.o.). Under these conditions no
      antiproliferative activity occurred in a model of "air dried" carotid artery
      injury. From these results we conclude that NO does not act as an
      antiproliferative agent under conditions where smooth muscle cell injury
      predominates.

PMID- 7717176
TI  - Activation of endothelial guanylate cyclase inhibits cellular reactivity.
AB  - The study shows that endothelial cells from human umbilical veins have a soluble
      guanylate cyclase which can be activated by sodium nitroprusside (SNP), SIN-1 (3
      morpholinosydnonimine) and S35b (4-methyl-3-phenylsulfonylfuroxan). Cells which
      were pretreated with these compounds showed an inhibition of thrombin-induced
      arachidonic acid release, PGI2 formation, PAF synthesis and PMNL adhesion.
      Endothelial guanylate cyclase can also be activated by nitric oxide (NO) which is
      generated in endothelial cells upon stimulation with thrombin or ionomycin. It is
      suggested that endogenously produced NO might control cell activation and
      endothelial function through a cGMP-dependent mechanism.

PMID- 7717177
TI  - Comparison of the vasorelaxing effect of different nitrovasodilators in
      conductive arterial and venous blood vessels.
AB  - We tested classically used organic nitrovasodilators such as s-nitroso-n-acetyl
      D,L-penicillamine, 3-morpholino-sydnonimine, pentaerythrityl-tetranitrate,
      isosorbide-dinitrate, isosorbide-mononitrate, glyceryl-trinitrate on different
      isolated conductive arterial and venous blood vessels of the same species
      (rabbit). We found an up to two orders of magnitude more pronounced
      venoselectivety in the systemic-circulation as compared to the lung-circulation.
      ISMN and PETN were most venoselective nitrovasodilators, with PETN being the most
      potent drug in all vessels studied.

PMID- 7717178
TI  - Glyceryl trinitrate but not spontaneous NO donors preserve myocardial function
      and cell integrity in ischemic rabbit hearts.
AB  - Langendorff-perfused rabbit hearts were subjected to 2 h of global, low-flow
      ischemia followed by 30 min of reperfusion. This resulted in a marked increase of
      left ventricular enddiastolic pressure and a loss in left ventricular creatine
      phosphokinase activity. NO formation was significantly reduced in early
      reperfusion. In the presence of superoxide dismutase (20 U/ml), NO release
      (oxyhemoglobin technique) was completely normalized, indicating inactivation of
      NO by superoxide radicals. Treatment with glyceryl trinitrate (GTN; 30 microM)
      prevented ischemia-induced myocardial tissue injury. SIN-1 (0.3 microM) was
      ineffective. These data demonstrate a protective effect of GTN but not SIN-1 in
      myocardial ischemia. It is concluded that the site of NO generation may play an
      important role in determining the biological activity of NO donating substances.

PMID- 7717179
TI  - Testosterone regulation of platelet and vascular thromboxane A2 receptors.
AB  - Testosterone has been implicated as a risk factor for cardiovascular diseases and
      thromboxane A2 (TXA2) plays a role in these diseases. We tested the notion that
      testosterone regulates the expression of TXA2 receptors in platelets and vascular
      smooth muscle. Testosterone significantly increased the density of TXA2 receptors
      in cultured rat aortic smooth muscle and human erythroleukemia cells, a
      megakaryocyte-like cell. Treatment of rats with testosterone resulted in a
      significant increase in platelet and aortic TXA2 receptor density and increased
      responsiveness to TXA2 mimetics. We conclude that testosterone regulates the
      expression of TXA2 receptors.

PMID- 7717180
TI  - Effects of NO-donors, SIN-1 and GEA 3175 on prostacyclin and cGMP synthesis in
      cultured rat endothelial cells.
AB  - The aim of the present study was to investigate, whether nitric oxide (NO)
      modifies prostacyclin synthesis in endothelial cells. Two different NO-donors:
      SIN-1 (3-morpholino sydnonimine) and GEA 3175 (4-aryl-substituted oxatriazol
      derivative), and the NO-synthesis inhibitor; L-NAME were used. Endothelial cells
      were incubated with the tested compounds with or without Ca ionophore A23187
      stimulation. SIN-1 (> 33 microM) and GEA 3175 (> 1 microM) increased the
      endothelial cGMP levels independently of A23187 stimulation. SIN-1 did not
      influence prostacyclin synthesis. GEA 3175 (> 33 microM) increased prostacyclin
      synthesis up to 2-fold, when incubated without A23187. GEA 3175 with A23187
      induced about 30% inhibition in prostacyclin synthesis. L-NAME decreased
      unstimulated prostacyclin synthesis and this inhibition was reversed by GEA 3175.
      Obviously NO is able to modulate prostacyclin synthesis, however, much higher
      concentrations are needed than those to increase cGMP synthesis.

PMID- 7717181
TI  - Effects of pentaerythrityl-tetranitrate and isosorbide-5-mononitrate in
      experimental atherosclerosis.
AB  - This study was performed to determine whether long-term treatment with organic
      nitrovasodilators exhibit pharmacological effects on the development of
      atherosclerotic lesions and endothelial dysfunction in the cholesterol fed
      rabbit. The major finding of this study is that PETN, but not ISMN, decreases the
      extent of aortic intimal lesions and the development of endothelial dysfunction.
      In addition, 15 weeks of feeding a diet enriched with either PETN or ISMN did not
      induce a measurable extent of vascular in-vitro tolerance to the vasodilator
      activity of these drugs.

PMID- 7717182
TI  - Effect of nitric oxide donors on rat bronchial muscle in vitro.
AB  - Relaxing effects of the nitric oxide donors GEA 3175 (3-aryl-substituted
      oxatriazole derivative), SIN-1 and sodium nitroprusside (SNP) were compared in
      the rat bronchial rings in vitro. In epithelium intact rings, after metacholine
      precontraction ED50 of GEA 3175 and SNP were similar (2 and 3.5 microM
      respectively) while the maximum effect of the former was bigger (92% and 54%
      respectively). SIN-1 was less potent (ED50 50 microMx, maximum 55%). In the
      absence of the epithelium the effect of GEA 3175 was attenuated, while that of
      SIN-1 or SNP were abolished. In the KCl precontracted rings the effects of all
      compounds were smaller than after metacholine precontraction. Removal of the
      epithelium did not alter the effects of GEA 3175 or SIN-1 but clearly increased
      that of SNP (change of EC50 from 10 to 0.7 microM).

PMID- 7717183
TI  - Rapid tolerance to formation of authentic NO from nitroglycerin in vivo.
AB  - Direct evidence for in vivo NO formation from nitroglycerin (GTN) was obtained by
      measurements of exhaled nitric oxide in anaesthetized. Infusions of GTN (1-100
      micrograms kg-1 min-1 i.v.) induced dose-dependent and biphasic increments in
      exhaled NO parallelled by reductions in systemic blood pressure. The NO detected
      during GTN infusion was unaffected by the nitric oxide synthase inhibitor L-NAME
      or acute i.v. administration of L-cysteine, N-acetyl-L-cysteine or glutathione.
      The present data demonstrate that NO is formed from GTN in vivo, and that
      tolerance in vivo is due to decreased formation of NO.

PMID- 7717184
TI  - The exercise-induced increase in plasma levels of endothelin-1 is enhanced in
      patients with atherosclerotic coronary artery disease. Modulation by
      pentaerithrityltetranitrat (PETN).
AB  - BACKGROUND AND OBJECTIVE: Previous studies have suggested that endothelin (ET)-1
      with its marked vasoconstrictive potency may play a role in the induction of
      coronary artery spasms. Furthermore, it was demonstrated using in-vitro vessel
      preparations that the secretion of ET-1 by the vascular endothelium is enhanced
      in the presence of atherosclerotic alterations. The objective of the present
      study was to investigate a) the effects of ergometric exercise on ET-1 plasma
      concentrations in 10 patients with coronary artery disease (CAD) as compared to
      an age and sex matched control group and b) the modulatory role of the orally
      administered organic nitrate, pentaerithrityltetranitrat (PETN), in patients with
      CAD. PATIENTS AND METHODS: 10 male patients with CAD confirmed by coronarography
      and 10 male healthy controls underwent a bicycle ergometry according to the WHO
      standards upt to 125 watts. Venous blood samples for determination of ANP and ET
      1 plasma concentrations were drawn in supine position directly before and 5 min
      after ergometric exercise. Subsequently, patients were randomized and treated for
      3 days in a crossover design either with placebo or PETN (150 mg b.i.d.).
      RESULTS: Basal plasma levels of ET-1 were 6.1 +/- 0.7 pg/ml (patients) and 5.5 +/
      0.6 pg/ml (controls), resp. (n.s.). After ergometric exercise ET-1 plasma
      concentrations rose significantly (7.3 +/- 0.9 pg/ml; p < 0.05) in the placebo
      treated patient group, whereas they remained constant (5.5 +/- 0.7 pg/ml) in the
      PETN-treated patient group. Blood pressure and heart rate were not modified by
      the PETN-treatment. ET-1 plasma levels remained unaffected by ergometric exercise
      in controls. DISCUSSION: In contrast to healthy controls ergometric exercise
      induced an increase in ET-1 plasma concentrations in patients with CAD that may
      be potentially harmful by promoting coronary vasospasms. The almost complete
      blunting of the ET-1-increase in the presence of PETN-therapy may result from
      local-hemodynamic effects of the organic nitrate; it may be hypothesized that the
      nitrate-induced rise in local NO-concentrations counteracts ET-secretion. The
      findings of the present study are in accordance with the beneficial clinical
      effects of organic nitrates in patients with CAD.

PMID- 7717185
TI  - Clinical relevance of endothelial dysfunction in cardiovascular disorders.
AB  - The potential role of endothelial dysfunction, defined by an imbalance in the
      production of endothelium-derived vasodilator and constrictor factors is
      discussed. Evidence is presented that increased endothelin-1 production plays an
      important role in the clinical and morphological manifestations of pulmonary
      hypertension, particularly in primary disease. As well, the potential
      contribution of a relative decrease in nitric oxide production to inappropriately
      elevated pulmonary vascular resistance in patients with secondary causes of
      pulmonary hypertension, particularly those with congestive heart failure is
      discussed.

PMID- 7717186
TI  - Endothelin and endothelin antagonists: pharmacology and clinical implications.
AB  - Endothelins (ET) are a family of peptides with potent biological properties.
      Endothelial cells produce exclusively ET-1 while other tissues produce ET-2 and
      ET-3. The production of ET requires an increase in intracellular Ca2+. This
      increase can be induced by physical chemicals (i.e. hypoxia) or receptor-operated
      stimuli (i.e. thrombin, angiotensin II, arginine vasopressin, transforming growth
      factor beta 1, interleukin-1). Most of ET is released abluminally towards
      vascular smooth muscle and less luminally. The main vascular effect of ET are
      vasodilation (transient), profound and sustained vasoconstriction as well as
      proliferation of vascular smooth muscle. These biological effects are mediated by
      distinct receptors. Three ET receptors have been cloned, i.e. ETA-, ETB- and ETC
      receptors. In vascular tissue ETA-receptors are expressed on vascular smooth
      muscle and responsible for vasoconstriction. ETB-receptors are expressed on
      endothelium and linked to nitric oxide and/or prostacyclin release. Activation of
      these receptors explains the transient vasodilation with intraluminal application
      of ET. Vascular smooth muscle cells can express ETB-receptors which contribute to
      ET-induced vasoconstriction particularly at lower concentrations. The role of the
      recently cloned ETC-receptor in the vasculature is still uncertain. ET production
      is increased (as judged from circulating plasma levels) in vascular disease and
      atherosclerosis in particular, in myocardial infarction and heart failure,
      pulmonary hypertension and renal disease. ET production is increased in arterial
      hypertension remains controversial. Non-peptidic ET antagonists have been
      developed which either block ETA- receptors or ETA- and ETB-receptors
      simultaneously. The advantage of ETA-receptors is that they leave the endothelium
      dependent vasodilation to ET (via ETB-receptor) intact. However, ETB-mediated
      contraction remains unaffected by these antagonists. In contrast ETA-/ETB
      antagonists fully prevent ET-induced vasoconstriction, however, they also inhibit
      the endothelial effects of the peptide. ET antagonists interfere with the effects
      of ET in isolated vascular tissue (including that obtained from humans) as well
      as in vivo. In humans, ETA as well as ETA-/ETB-antagonists inhibit endothelin
      induced vasoconstriction. Hence in summary ET are a family of potent peptides
      with profound effects in the vasculature. Several studies suggest a role of ET in
      cardiovascular disease. The newly developed ET-antagonists are potent and
      selective tools to delineate the (patho-)physiological roles of ET and may become
      a new class of cardiovascular drugs.

PMID- 7717187
TI  - Platelet-vessel wall interactions, focal adhesions, and the mechanism of action
      of endothelial factors.
AB  - Endothelial cells produce a variety of vasoactive substances including
      prostacyclin (PGI2) and endothelium-derived relaxing factor (EDRF/NO) which are
      potent inhibitors of platelet adhesion/aggregation and vascular smooth muscle
      cell contraction/proliferation. PGI2 and EDRF elevate cAMP or cGMP, respectively,
      in vascular cells and other targets. The intracellular effects of cAMP and cGMP
      in vascular smooth muscle cells and platelets are primarily mediated by the
      family of cAMP- and cGMP-dependent protein kinases and their substrates.
      Important effector systems include enzymes, channels and regulatory proteins
      responsible for the regulation of intracellular Ca++. Other evidence suggests
      that VASP, a focal adhesion protein phosphorylated in platelets and smooth muscle
      cells in response to PGI2 and EDRF, is important for the regulation of integrins
      and cell-matrix interactions.

PMID- 7717188
TI  - The effects of intracellular Ca2+ concentration and hypoxia on basal endothelin-1
      secretion by cultured porcine aortic endothelial cells.
AB  - When the intracellular free Ca2+ concentration ([Ca2+]i) of porcine aortic
      endothelial cells incubated in normoxic or hypoxic atmosphere was varied more
      than tenfold, basal endothelin-1 (ET-1) secretion was maximal at control
      conditions ([Ca2+]i = 190 nM) and reduced at lower and higher [Ca2+]i. High
      [Ca2+]i reduced ET-1 synthesis only in part via activation of the NO/cGMP system.
      Our results provide evidence that basal ET-1 secretion is regulated by [Ca2+]i,
      and that Ca2+ plays a similar role in hypoxic and normoxic signal transduction.

PMID- 7717189
TI  - Formation of 8-iso-prostaglandin F2 alpha by human platelets.
AB  - F2-isoprostanes are free radical catalyzed prostaglandin F2 isomers formed from
      arachidonic acid in an enzyme independent manner (1). Analogous families of other
      prostaglandin isomers have also been described. Detection of these compounds in
      vivo has been postulated to represent an approach to the quantitative assessment
      of free radical generation in humans (2). Additionally, the 8-iso analogues of
      PGF2 alpha and PGE2 have been shown to induce vasoconstriction, a response which
      is prevented by pharmacological antagonists of the thromboxane receptor (3).
      Consequently, it is conceivable that these particular isomers might exhibit an
      autacoidal function. We chose to explore the factors which regulate the
      biosynthesis of one of these compounds, 8-iso-PGF2 alpha, in vivo and by human
      platelets in vitro, to understand more clearly how the discovery of these
      compounds might be exploited to further our understanding of free radical
      catalyzed processes in vivo.

PMID- 7717190
TI  - The similarity in action of hypoxia and platelet-activating factor on smooth
      muscle cells of coronary arteries: possible explanation for hypoxic coronary
      spasm development.
AB  - Studies in isolated smooth muscles and single cells of coronary arteries have
      demonstrated that both hypoxia and platelet activating factor (PAF) in a similar
      manner increased contractile force and Ca-activated K currents. The specific
      antagonists of PAF receptors BN 52021 and WEB 2886 significantly decreased
      contractile responses of vascular smooth muscle (VSM) to PAF and hypoxia. Taken
      together, these data allow to suggest that endogenous PAF can produce both phasic
      and tonic contraction in coronary arteries under hypoxic condition.

PMID- 7717191
TI  - Pituitary adenylate cyclase activating peptides are endothelium-independent
      dilators of human and porcine coronary arteries.
AB  - The PACAPs have been shown to be potent vasodilators in different animal species.
      Data in humans are still lacking. Therefore we investigated the effects of PACAP
      38, PACAP 27 and VIP on isolated human and porcine coronary arteries (HCA and
      PCA). Our data show, that the PACAPs are endothelium-independent vasorelaxants,
      which in HCA are slightly more potent than VIP. The N-terminal shortened peptides
      PACAP 6-38 and PACAP 6-27 also show relatively potent vasorelaxant effects,
      acting as partial agonists. Glibenclamide, a selective inhibitor of ATP-sensitive
      potassium channels, partially reverses the effects of the PACAPs, indicating an
      involvement of these channels in the mechanism of action.

PMID- 7717192
TI  - Coupling of hepoxilin A3-specific binding with calcium-mobilizing actions in
      human neutrophils.

PMID- 7717193
TI  - Role of intracellular calcium in the regulation of phospholipase A2 in fMet-Leu
      Phe-challenged human polymorph neutrophils.
AB  - In the present study, we have shown that the protein kinase C (PKC) inhibition by
      staurosporine augmented fMet-Leu-Phe-(FMLP)-induced arachidonic acid (AA) release
      in human polymorph neutrophils (PMN). This effect is in contradiction to a
      recently reported mechanism that besides Ca2+, the phosphorylation of cytosolic
      phospholipase A2 (cPLA2) is essential for the enzyme activation. In addition, we
      found that staurosporine elevated the basal concentration of intracellular Ca2+,
      although initial Ca2+ release was not affected. Since thapsigargin, a blocker of
      endogenous Ca2+ ATPase, also increased AA release dose-dependently, we believe
      that the elevation of intracellular Ca2+ is the most essential step and not the
      phosphorylation of enzyme for the activation of cPLA2.

PMID- 7717194
TI  - Thrombin receptor activating peptide-induced cellular effects: comparative
      studies on human platelet activation and endothelium-dependent relaxation of
      porcine pulmonary arteries.
AB  - The thrombin receptor activating peptides with 6 and 14 amino acids (TRAP-6,TRAP
      14) caused aggregation of washed platelets as well as of platelets in citrated
      and hirudin plasma. Stimulation of platelets was associated with an increase in
      cytosolic Ca2+ and formation of thromboxane. In porcine pulmonary arteries they
      induced reversible endothelium-dependent relaxation of precontracted vessels via
      release of endothelium-derived nitric oxide. TRAP-6 and TRAP-14 did not differ in
      their intrinsic activity. Both peptides possess thrombin-like activity, but their
      potency is more than three orders of magnitude lower than that of thrombin.

PMID- 7717195
TI  - Inositol 1,4,5-triphosphate and protein kinase C are involved in thrombin- and
      trap-induced vascular smooth muscle contraction.
AB  - Thrombin (30 nmol/l) as well as the thrombin receptor activating peptide (TRAP),
      10 mumol/l) induce a sustained contraction of endothelium-denuded porcine
      pulmonary arteries. The first phasic component of contraction is associated with
      the generation of IP3 which precedes the development of contractile force. Since
      the PKC inhibitor staurosporine (50 nmol/l) completely inhibits the tonic
      contraction this component of contraction seems to be due to the activation of
      protein kinase C (PKC). The thrombin- and TRAP-induced vasoconstriction strongly
      depends on extracellular calcium; the remaining thrombin- or TRAP-induced
      contraction in Ca(2+)-free medium seems to be attributed to the IP3-mediated
      release of calcium from intracellular stores.

PMID- 7717196
TI  - Isolation and functional characterization of DNA-derived aptamers that act as
      thrombin inhibitors in human platelets and coagulation assays.
AB  - Aptamer sequences were isolated from defibrotide, a single-stranded, commercial
      DNA preparation and studied for thrombin inhibitory activity. Three different
      aptamers were identified, sequenced and their biological activity was determined
      in platelet aggregation and coagulation assays. All aptamers were potent
      inhibitors of thrombin-induced platelet aggregation and thromboxane formation and
      prolonged the thrombin time in human plasma. There was no effect of any of these
      compounds when a thromboxane mimetic (U 46.1619), collagen or thrombin activating
      peptide (TRAP-6) were used as agonists, excluding a nonspecific binding of the
      compounds to the thrombin receptor. The data suggest that thrombin-inhibitory
      aptamers are present in the mammalian genome and may constitute an endogenous
      antithrombin system.

PMID- 7717197
TI  - Defibrotide's activity on leukocytes and platelets in rabbits with diet-induced
      atherosclerosis.
AB  - Oral Defibrotide decreased leukocyte and platelet counts, raised by cholesterol
      diet, and the area (%) of aorta endothelial surface involved in atherosclerosis.
      Frequency of intimal thickening in blood vessels of kidneys and hearts and in
      cardiac valves was reduced by oral Defibrotide by 47%, 29% and 17%. It is
      suggested that oral Defibrotide reduced the involvement of the aorta in the
      atherosclerotic process by acting on leukocytes and platelets, to both reduce
      their number and deactivate them.

PMID- 7717198
TI  - Regulation of prostaglandin receptors in myocardial ischemia.
AB  - Sarcolemmal membranes from pig hearts express a homogenous class of binding sites
      for [3H]PGE1. Competition binding studies with EP receptor suptype selective
      ligands suggest an EP3 receptor subtype. The GTP analogue GTP gamma S reduced
      affinity without changing binding capacity, indicating a G protein coupled EP3
      receptor. Regional myocardial ischemia (60 min) in anesthetized, open-chest pigs
      caused a 50% increase of the number of binding sites while GTP gamma S still
      decreased [3H]PGE1 binding, suggesting intact G protein coupling. Myocardial
      ischemia may, therefore, modify myocardial actions of prostaglandins.

PMID- 7717199
TI  - Hydroxylated 22-carbon fatty acids in platelet and vascular smooth muscle
      function: interference with TXA2/PGH2 receptors.
AB  - Sub-micromolar levels of the lipoxygenase products of n-3 fatty acids
      specifically antagonize both the contractile effects of thromboxane (U46619) and
      its platelet aggregating effect. In addition, OH-22:6n3 inhibits thromboxane
      induced decreases in cerebral blood flow of the rat. Analysis of binding
      parameters indicates these derivatives induce a marked decrease in the affinity
      of the TXA2/PGH2 receptor for thromboxane with a mild change in the number of
      receptor sites. The 22-carbon n-3 hydroxy fatty acids are the most potent
      biological antagonists of thromboxane in comparison to the n-6 hydroxy fatty
      acids and their parent fatty acids. Dietary permutations modify the hydroxy fatty
      acid profile and correlate with changes in thromboxane-mediated responses.

PMID- 7717200
TI  - Increased permeability of bovine aortic endothelial cell monolayers in response
      to a thromboxane A2-mimetic.
AB  - The present study was designed to investigate the ability of thromboxane to
      modulate the clearance rate of 125I-albumin through bovine aortic endothelial
      cell (BAEC) monolayer grown on polycarbonate micropore membrane. Stimulation of
      BAEC with the TXA2 mimetic U44069 (10(-8), 10(-7) and 10(-6) M) elicited a dose
      dependent increase of labeled albumin passage across BAEC monolayers. This effect
      was markedly reduced by the TXA2 antagonist L655240 (10(-7) and 10(-6) M). Our
      results suggest that TXA2 may modulate the permeability of endothelial cells
      directly through activation of specific receptors.

PMID- 7717201
TI  - Potentiation of PDGF-induced growth responses in coronary artery smooth muscle
      cells by thromboxane.
AB  - Mitogenic effects of TXA2 in vascular smooth muscle cells are discussed to be
      dependent on the age of the donor organism. The present study investigates the
      contribution of TXA2 on PDGF-induced proliferation of bovine coronary artery
      smooth muscle cells (BCA-SMC) isolated from adult animals. Radioligand binding
      studies revealed high affinity TXA2 binding sites (Kd = 1.6 nM) in these cells.
      TXA2-mimetics alone showed no proliferative effect in BCA-SMC, assessed by
      [3H]thymidine incorporation. However, PDGF-stimulated proliferation was
      potentiated two-fold receptor-dependently by TXA2-mimetics. Thus,
      vasoconstrictory eicosanoids released from activated platelets might aggravate
      proliferation of vascular smooth muscle cells at sites of vessel injury in the
      adult organism.

PMID- 7717202
TI  - The induction of cyclooxygenase-2 elicited by endotoxin in endothelial cells and
      macrophages is inhibited by prostaglandin E1 and 13,14-dihydro prostaglandin E1.
AB  - The effects of PGE1 or 13,14-dihydro PGE1 (PGE0) on the expression of COX-2
      protein and COX activity elicited by LPS (1 microgram/ml for 24 h) in bovine
      aortic endothelial cells (BAEC) and J774.2 macrophages were investigated. PGE1 or
      PGE0 (0.001 to 10 micrograms/ml) caused a dose-dependent decrease of COX activity
      elicited by LPS in both cell types. Western blot analysis showed that PGE1 or
      PGE0 (1 microgram/ml) inhibited the expression of COX-2 protein in LPS-activated
      BAEC and J774.2 macrophages. Thus, PGE1 or (its metabolite) PGE0 decrease the
      formation of COX metabolites by inhibiting the induction of COX-2 protein by LPS.

PMID- 7717203
TI  - Effects of prostaglandin E1, prostaglandin E0 and SPM 206 on isolated human
      coronary arteries.
AB  - The effects of PGE1, PGE0 and the stable PGE1-analogue SPM 206 on human
      epicardial coronary arteries were studied in vitro. The tension of the isolated
      arterial rings was measured isometrically. After precontraction, concentration
      response curves with the compounds were performed. PGE1 and SPM 206 elicited
      concentration-dependent relaxations which are counteracted by a contractile
      action in higher concentrations. In PGE0, the contractile action occurred even in
      lower concentrations. This contraction was antagonized by the selective
      thromboxane A2 antagonist SQ 29,548, resulting in an equipotent relaxation for
      all three compounds.

PMID- 7717204
TI  - Transjugular intrahepatic portosystemic shunts: current status.
AB  - The management of acute variceal hemorrhage from portal hypertension has
      traditionally included pharmacologic agents, mechanical compression with
      tamponading balloons, and endoscopic techniques including sclerotherapy and
      variceal banding. The role of operative portosystemic shunting has diminished in
      the past several years because of unpredictable postoperative morbidity from
      hepatic failure or encephalopathy [1-8]. Although orthotopic liver
      transplantation provides a unique and effective solution to these problems, it is
      often impractical in the emergent setting and may not be necessary if the
      hemorrhage can be reliably controlled by other means. The transjugular
      intrahepatic portosystemic shunt (TIPS) was developed to relieve portal
      hypertension without the mortality and morbidity of an open surgical procedure.
      This review summarizes the salient history, technique, and results of this
      procedure. The evolving role of TIPS in the management of portal hypertension,
      including indications, contraindications, and the durability of the procedure, is
      assessed.

PMID- 7717205
TI  - Evaluation of developmental dysplasia, Perthes disease, and neuromuscular
      dysplasia of the hip in children before and after surgery: an imaging update.
AB  - This article focuses on the current status of radiologic imaging before and after
      surgery of a limited spectrum of common hip disorders in children: developmental
      hip dysplasia, Legg-Calve-Perthes disease, and neuromuscular hip dysplasia. An
      understanding of the anatomic abnormality, of when surgical intervention is
      needed, of the types of surgery, and of the complications influences the ability
      of the radiologist to interpret radiologic studies and to communicate information
      to the referring physician. Technologic advances in imaging that provide new
      information about the developing hip and standard radiographic evaluation of the
      abnormal hip are discussed. The diagnostic and treatment goals for all types of
      hip disease are similar. The goals of all therapy are to preserve the full range
      of motion of the hip and to prevent premature degenerative changes by maintaining
      a round, well-shaped femoral head that is contained by and congruous with the
      acetabulum.

PMID- 7717206
TI  - Metastases: mechanisms, pathways, and cascades.
AB  - Metastases are the major cause of treatment failure in cancer patients. Sixty
      percent of patients with newly diagnosed solid tumors (excluding skin cancers
      other than melanoma) have clinically evident or microscopic metastases when the
      primary tumor is diagnosed [1]. Dissemination of malignant cells throughout the
      body and their survival to form secondary growths constitute a complicated
      process dependent on both host and tumor properties. This review outlines the
      mechanisms involved in the metastatic process, the pathways of tumor spread
      throughout the body, and the common routes used by various tumors.

PMID- 7717207
TI  - Copyright law and academic radiology: rights of authors and copyright owners and
      reproduction of information.
AB  - Desktop computer hardware and software provide many new and accessible avenues
      for increased academic productivity, but some activities may have legal
      implications. The advent of technologies such as scanners, the ever-increasing
      number of electronic bulletin boards, and the development of the "information
      superhighway" affect the concept of copyright and require authors and publishers
      to reconsider their legal rights and obligations when they create or publish new
      works or modify existing ones. For example, with desktop scanners, almost any
      image, published or otherwise, can be copied, enhanced, and manipulated.
      Moreover, many radiologists have access to copyrighted digital radiologic
      teaching file images, such as those from the University of Iowa or the University
      of Washington, which are available (and "downloadable") on the Internet. Because
      "downloading" (or "uploading") a document or image is essentially making a copy
      of that document or image, copyright laws and the rights that they afford authors
      are involved.

PMID- 7717209
TI  - Diffuse endobronchial non-Hodgkin's lymphoma: CT demonstration.

PMID- 7717208
TI  - Widening of the tracheal bifurcation on chest radiographs: value as a sign of
      left atrial enlargement.
AB  - OBJECTIVE: This study evaluated widening of the tracheal bifurcation (subcarinal
      and interbronchial) angle on posteroanterior chest radiographs as a sign of left
      atrial enlargement. The purpose was to determine the diagnostic sensitivity and
      specificity of the sign. MATERIALS AND METHODS: The chest radiographs and
      echocardiograms of 122 clinically stable patients were retrospectively reviewed.
      The mean interval between examinations was 10 days (range, 0-30 days). The left
      atrial dimension was measured on the two-dimensional echocardiograms. Sixty-five
      patients had a normal left atrial dimension (mean, 34 mm), and 45 patients had an
      enlarged atrium (mean, 47 mm) on echocardiography. Subcarinal and interbronchial
      angles were jointly measured by two observers who were unaware of the
      echocardiographic findings. Correlation analysis was used to determine which
      angle measurement best predicted the left atrial size. Discriminant analysis was
      used to derive a threshold angle that predicted left atrial enlargement. RESULTS:
      The carina was inadequately seen on 14 radiographs. Left atrial size correlated
      poorly with both the interbronchial (r = .33) and the subcarinal (r = .25) angel
      values. An interbronchial angle of 76.4 degrees and a subcarinal angle of 65.4
      degrees were the best discriminators between patients with normal and those with
      enlarged left atrial dimensions (sensitivities, 61% and 51%, respectively;
      specificities, 63% and 66%). CONCLUSION: Our findings show that widening of the
      tracheal bifurcation angle on chest radiographs is an insensitive and nonspecific
      sign of left atrial enlargement. This sign is of little value in diagnosing left
      atrial enlargement.

PMID- 7717210
TI  - Anomalous origin of the left coronary artery: diagnosis by coronary MR
      angiography.

PMID- 7717211
TI  - Pneumocystis carinii pneumonia.

PMID- 7717212
TI  - The comparative value of mammographic screening for women 40-49 years old versus
      women 50-64 years old.
AB  - OBJECTIVE: The purpose of our study was to compare the major prognostic factors
      (tumor size, axillary lymph node status, and tumor stage) of breast cancers
      detected at mammographic screening in women ages 40-49 years old with those in
      women ages 50-64 years old. MATERIALS AND METHODS: Study subjects were women ages
      40-64 years old who participated in our mobile van mammographic screening program
      from April 1985 to June 1994. We retrospectively reviewed the clinical and
      pathology records of women in whom breast cancer was detected at mammographic
      screening. All examinations were performed with dedicated equipment using screen
      film technique. RESULTS: A total of 44,301 screening examinations were done
      during the study period. Seventy-five cancers were detected in women ages 40-49
      years old, and 128 cancers were detected in women ages 50-64 years old. The
      cancer detection rate was 3.0 per 1000 examinations in the younger age group
      compared with 5.5 per 1000 examinations in the older age group. The median size
      of breast cancers was 10 mm for women ages 40-49 versus 11 mm for women ages 50
      64. Eighty-eight percent of the patients in both age groups had no evidence of
      metastasis to axillary lymph nodes. Nineteen percent of women in the younger age
      group had advanced breast cancer (stage II or higher) compared with 26% of women
      ages 50-64 (p = .25). No statistically significant differences were noted between
      the two age groups in the size, lymph node status, or stage of breast cancers
      detected at mammographic screening. However, the cancers found in younger women
      had slightly more favorable prognoses. CONCLUSION: The major prognostic factors
      of cancers detected with modern mammographic equipment appear to be at least as
      favorable for women ages 40-49 years old as for women ages 50-64 years old. As
      mammographic screening has already been shown to be beneficial for women ages 50
      64 years old, screening should also be beneficial for women ages 40-49 years old.

PMID- 7717213
TI  - Screening mammography in women 40-49 years old.

PMID- 7717214
TI  - Initial versus subsequent screening mammography: comparison of findings and their
      prognostic significance.
AB  - OBJECTIVE: The goal of this study was to compare findings on initial and
      subsequent screening mammograms to determine the prognostic significance of
      screening-detected abnormalities. MATERIALS AND METHODS: All 3386 abnormal
      examinations from a 9-year mammographic screening program were studied. An
      initial examination was defined as one for which there were no prior films
      available for comparison (even if one or more prior examinations had been
      performed); the remainder were called subsequent examinations. The principal
      mammographic feature of each abnormality was recorded, as well as whether a
      biopsy was performed. For all screening-detected cancers, we also determined
      several surrogate markers of prognosis (tumor size, presence of axillary lymph
      node metastasis, and tumor stage). These various parameters were analyzed as a
      function of initial versus subsequent screening. RESULTS: The frequency of
      abnormal examinations was more than 2 times greater for initial examinations (7%)
      than for subsequent examinations (3%). Only minor differences were noted between
      initial and subsequent screenings when comparing the principal mammographic
      features of the abnormalities. However, the number of cancers found per number of
      biopsies performed was significantly greater (p = .02) for subsequent screenings
      (41%) than for initial screenings (32%). Among the 333 cancers detected, tumor
      size was significantly smaller for subsequent screenings (p = .0076). Node
      negative status and early tumor stage (stage 0 or 1) also were found more
      frequently for subsequently screened cancers, but these differences were not
      statistically significant. CONCLUSION: Substantially fewer abnormal screening
      interpretations are made when mammography has been performed previously and when
      the prior films are available for comparison. This results in cost savings and
      reduced morbidity at subsequent screening (no further work-up, less patient
      anxiety, fewer benign biopsies). Surrogate markers of prognosis also appear to be
      more favorable for cancers detected at subsequent screening.

PMID- 7717215
TI  - Atypical ductal hyperplasia diagnosed at stereotaxic core biopsy of breast
      lesions: an indication for surgical biopsy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the prevalence of carcinoma
      found at surgical biopsy of lesions identified as atypical ductal hyperplasia by
      stereotaxic core breast biopsy. SUBJECTS AND METHODS: Stereotaxic core biopsies
      of 264 mammographically evident lesions were done with the patients lying prone
      on a dedicated stereotaxic table, with an automated gun and a 14-gauge needle.
      Atypical ductal hyperplasia was identified in 25 (9%) of 264 lesions, including
      four (3%) of 159 masses and 21 (20%) of 105 lesions evident as calcifications.
      Surgical biopsy was recommended in all 25 of these cases and was performed in 21.
      Results of stereotaxic core biopsy and surgery in these 21 cases were reviewed
      and correlated. RESULTS: Of 21 cases identified as atypical ductal hyperplasia at
      stereotaxic core biopsy that were subsequently evaluated with surgical biopsy,
      histopathologic analysis of the surgical specimen yielded benign histologic
      findings without atypia in four (19%), atypical ductal hyperplasia in six (29%),
      and carcinoma in 11 (52%). Of the 11 carcinomas, histologic findings showed
      ductal carcinoma in situ in eight (73%) and invasive ductal carcinoma in three
      (27%). CONCLUSION: The finding of atypical ductal hyperplasia at stereotaxic core
      breast biopsy is an indication for surgical biopsy because of the high prevalence
      of ductal carcinoma in these lesions.

PMID- 7717216
TI  - Erdheim-Chester disease involving breast and muscle: imaging findings.

PMID- 7717217
TI  - Detection of transjugular intrahepatic portosystemic shunt dysfunction: value of
      duplex Doppler sonography.
AB  - OBJECTIVE: Recent reports have shown that a high percentage of patients with
      transjugular intrahepatic portosystemic shunts (TIPS) have postprocedural shunt
      complications, including thrombosis of the stent, stenosis of the stent, or
      stenosis of the hepatic vein draining the stent. We did a prospective study to
      determine the utility of Doppler sonography as a screening technique for the
      detection of these complications. SUBJECTS AND METHODS: From September 1991 to
      September 1992 we placed TIPS in 45 patients. After the procedure, patients were
      routinely evaluated with both Doppler sonography and angiography. The sonographic
      protocol consisted of insonation of the stent, portal vein, and hepatic vein to
      determine the presence of flow, peak velocity, and direction of flow. The
      angiograms were evaluated for stenoses of the stent or hepatic vein that caused
      an increase in the portosystemic pressure gradient greater than 15 mm Hg,
      increased intrahepatic portal venous filling, retrograde filling of the draining
      hepatic vein, or opacification of varices. The sonographic findings were
      statistically evaluated to determine if sonography could demonstrate the
      complications shown by angiography. RESULTS: Adequate follow-up was obtained in
      29 of the 45 patients. Sixteen of the 29 patients had shunt complications that
      consisted of one stent thrombosis, three stent stenoses, nine hepatic vein
      stenoses, and three concomitant stenoses of the stent and hepatic vein. Flow was
      not detected by sonography in the stent of the patient with thrombosis. There was
      a significant difference (p = .003) between the temporal change in peak stent
      velocity in patients with stenoses versus those without. Use of a change
      (increase or decrease) in peak stent velocity greater than 50 cm/sec from the
      post-TIPS baseline sonogram as the diagnostic criterion for the detection of
      shunt stenoses resulted in a 93% sensitivity and 77% specificity. Five patients
      with stenosis had reversed flow in the draining hepatic vein. Only one patient
      with a stenosis had a peak stent velocity less than 50 cm/sec. CONCLUSION: Our
      results suggest that Doppler sonography is an excellent noninvasive screening
      technique for the detection of complications of TIPS. We have found a temporal
      change in peak stent velocity greater than 50 cm/sec to be a more sensitive
      sonographic sign of TIPS stenosis than the previously reported low-velocity
      parameters. Our experience suggests that nearly all complications of TIPS can be
      detected by using three criteria: (1) no flow for thrombosis, (2) a temporal
      change in peak stent velocity greater than 50 cm/sec for stent and/or hepatic
      vein stenosis, and (3) reversed flow in the hepatic vein draining the stent for
      hepatic vein and, rarely, stent stenosis.

PMID- 7717218
TI  - Portal vein thrombosis after percutaneous ethanol injection for hepatocellular
      carcinoma: value of color Doppler sonography in distinguishing chemical and tumor
      thrombi.
AB  - OBJECTIVE: The distinction between benign (chemical) and tumor thromboses of the
      portal vein after treat,ent with percutaneous injection of ethanol for
      hepatocellular carcinoma is crucial for the proper management of the patient. The
      purpose of this study was to determine whether color Doppler sonography can be
      used to differentiate between the two types of thrombi. SUBJECTS AND METHODS:
      Between October 1991 and April 1994, portal vein thrombosis was detected by color
      Doppler sonography in 19 patients (13 men and six women 59-77 years old; mean
      age, 67 years) who had hepatocellular carcinomas and who had received
      percutaneous ethanol injection (n = 11) or percutaneous ethanol injection after
      transcatheter arterial embolization (n = 8). The criterion for diagnosing tumor
      thrombosis by color Doppler sonography was the detection of pulsatile arterial
      flow in the thrombus. The benign or malignant nature of the thrombosis was
      subsequently established by percutaneous fine-needle biopsy of the thrombus;
      malignant thrombosis was seen in 13 patients, and chemical thrombosis was seen in
      six patients. RESULTS: Pulsatile arterial flow in the thrombus was observed by
      color Doppler sonography in 12 of the 13 malignant thrombi and in none of the
      bland thrombi. The flow was hepatopetal in seven cases and hepatofugal in five
      cases. The peak systolic frequency shift ranged from 0.59 to 2.65 kHz (mean, 1.35
      kHz), and the resistive index ranged from 0.37 to 0.69 (mean, 0.55). The
      sensitivity and the specificity of color Doppler sonography for the detection of
      tumor thrombosis were 92% and 100%, respectively. CONCLUSION: Our study shows
      that color Doppler sonography is a reliable way to differentiate between chemical
      and tumor thromboses of the portal vein in patients with hepatocellular
      carcinomas treated by ethanol injection. When the sonogram shows pulsatile
      arterial flow within the thrombus, percutaneous biopsy of the thrombus is
      unnecessary. The finding is always indicative of malignant thrombosis.

PMID- 7717219
TI  - Characterization of focal hepatic lesions with duplex sonography: findings in 198
      patients.
AB  - OBJECTIVE: The purpose of this study was to determine the value of duplex Doppler
      sonography in the characterization of focal hepatic lesions. SUBJECTS AND
      METHODS: Duplex Doppler sonography with a 3-MHz transducer was performed
      prospectively on 198 patients with focal hepatic lesions. One hundred thirty-two
      patients had pathologically proved diagnoses, confirming 46 hepatomas and 86
      metastatic lesions. Twenty-three hemangiomas were confirmed either with tissue,
      tagged RBC study, MR imaging, or hemangioma CT protocol. Forty-three patients
      with no history of cancer had benign lesions that were established on the basis
      of follow-up imaging and at least a 2-year clinical history with no evidence of
      cancer. RESULTS: Thirty-two hepatomas and four metastatic lesions had Doppler
      shifts of 4.5 kHz or more, giving a 70% sensitivity, 95% specificity, and 89%
      positive predictive value in distinguishing hepatomas from metastatic lesions.
      Forty-three hepatomas, 47 metastatic lesions, one hemangioma, and three benign
      lesions had Doppler shifts of 1.75 kHz or more, giving a 68% sensitivity, 94%
      specificity, and 96% positive predictive value in distinguishing malignant from
      benign lesions. Doppler shifts (mean +/- SD) were as follows: hepatomas, 4.72 +/-
      1.72 kHz; metastases, 1.99 +/- 1.63 kHz; and hemangiomas, 0.53 +/- 0.75 kHz.
      These differences in mean Doppler shifts were statistically significant (p <
      .0001). CONCLUSION: Duplex Doppler sonography aids in distinguishing hepatomas
      from metastases and malignant from benign hepatic lesions with a high degree of
      specificity but low sensitivity.

PMID- 7717220
TI  - Focal sparing of segment IV in fatty livers shown by sonography and CT:
      correlation with aberrant gastric venous drainage.
AB  - OBJECTIVE: One of the most common sites of focal sparing in fatty livers (focal
      spared area) shown by sonography or CT is the posterior edge of segment IV. The
      differentiation of such a focal spared area from tumor has been a diagnostic
      challenge. The purpose of this study was to determine if a correlation exists
      between the focal spared area at the posterior edge of segment IV in fatty liver
      and the decrease of portal perfusion from the main portal vein due to aberrant
      gastric venous drainage directed into segment IV. SUBJECTS AND METHODS: Seventeen
      patients with fatty liver diagnosed on the basis of sonographic and CT findings
      who had hepatic arteriography and/or CT during arterial portography (CTAP) were
      included in the study. Seven patients had a focal spared area more than 2 cm in
      the longest diameter at the posterior edge of segment IV, and 10 patients did not
      have a focal spared area. The frequency of aberrant gastric venous drainage shown
      by arteriography (17 patients) and/or by CTAP (15 patients) was compared in the
      two groups of patients. RESULTS: Hepatic arteriography showed aberrant gastric
      venous drainage in all patients who had a spared area, and CTAP showed a portal
      perfusion defect at the posterior edge of segment IV in all five patients with a
      focal spared area who underwent CTAP. On the other hand, no definite aberrant
      gastric venous drainage and portal perfusion defect were seen in any patient
      without a spared area. The difference in the frequency of aberrant gastric venous
      drainage between the two groups of patients was statistically significant (chi
      square test, p < .0001). CONCLUSION: Our results show that a strong correlation
      exists between the focal spared area at the posterior edge of segment IV in fatty
      liver and aberrant gastric venous drainage directed to segment IV. Focally
      decreased blood flow from the main portal vein associated with aberrant gastric
      venous drainage is a likely cause of the focal spared area. This fact is
      important for the differential diagnosis of hepatic tumors.

PMID- 7717221
TI  - Nontumorous low-attenuation defects in the liver on helical CT during arterial
      portography: frequency, location, and appearance.
AB  - OBJECTIVE: Low-attenuation defects in the liver that are caused by variations in
      the portal perfusion of the liver rather than by intrahepatic tumor can be
      detected using helical CT during arterial portography (CTAP). The purpose of this
      study was to characterize these nontumorous low-attenuation defects detected with
      helical CTAP in terms of their frequency, location, and appearance. MATERIALS AND
      METHODS: Helical CTAP examinations of 89 patients referred for preoperative
      evaluation of metastatic or primary liver tumors performed over a 20-month period
      were retrospectively reviewed by three radiologists. The frequency, appearance,
      and location of focal (within a subsegment) and diffuse (affecting more than one
      subsegment) nontumorous perfusion defects were determined. Findings on helical
      CTAP images were correlated with surgical findings (53 patients), results of MR
      examinations (25 patients), and follow-up CT examinations (11 patients). RESULTS:
      Ninety-seven nontumorous perfusion defects were identified in 68 patients. The
      most frequent defects were located adjacent to the gallbladder fossa (35),
      anterior to the porta hepatis (34), in the subcapsular portion of the liver (13),
      and adjacent to the falciform ligament (12). Nontumorous perfusion defects
      characteristically appeared wedge-shaped or flat and ranged in size from 8-20 mm.
      CONCLUSION: Nontumorous perfusion abnormalities have characteristic appearances
      and locations on helical CTAP examinations and are more common than previously
      reported with conventional CTAP. Familiarity with the locations and
      characteristic appearances of these defects is essential to prevent false
      positive diagnoses, so that operative candidates are not mistakenly denied
      surgical therapy.

PMID- 7717223
TI  - Fibrolamellar hepatocellular carcinoma: stage at presentation and results of
      aggressive surgical management.
AB  - OBJECTIVE: The purpose of this study was to report the stage of fibrolamellar
      carcinoma at presentation and the imaging findings of postoperative recurrent
      tumor in an aggressively managed population and to assess the implications of
      those findings relative to the patients' management. MATERIALS AND METHODS:
      Imaging studies in 10 patients with pathologically proved fibrolamellar carcinoma
      were reviewed. Preoperative studies included CT (n = 10), sonography (n = 8), and
      MR imaging (n = 2). Postoperative studies included CT (n = 9), sonography (n =
      4), and MR imaging (n = 1). Imaging findings were correlated with clinical and
      surgical follow-up data. Patients were followed up for 2-75 months (median, 26
      months). RESULTS: At presentation, seven (70%) of 10 patients had metastatic
      lymphadenopathy. Seven patients (70%), including four with lymph node metastasis,
      had tumor resections with intent to cure. Postoperative imaging studies revealed
      recurrent tumor in all seven of these patients, including six patients (86%) who
      had intrahepatic recurrence with or without lymph node metastasis after 6-18
      months, and one patient (14%) who had distant metastases 66 months
      postoperatively. Recurrent lesions were subsequently resected in three (43%) of
      seven patients, who were disease-free at a mean of 8 months after their second
      resection. Five patients died after 9 months mean survival, and two patients were
      alive with residual tumor after 3 months mean follow-up. CONCLUSION:
      Fibrolamellar carcinomas are often of advanced stage at diagnosis. Recurrence
      after resection with intent to cure is common. Early and frequent follow-up
      imaging is necessary for optimizing surgical management in patients with
      fibrolamellar carcinoma.

PMID- 7717222
TI  - Blood-pool MR contrast material for detection and characterization of focal
      hepatic lesions: initial clinical experience with ultrasmall superparamagnetic
      iron oxide (AMI-227).
AB  - OBJECTIVE: AMI-227 is an ultrasmall superparamagnetic iron oxide colloid known to
      enhance tissue T1 and T2 relaxation rates. Animal studies show that AMI-227 has
      an estimated blood half-life of more than 200 min. In this study, we evaluated
      the clinical utility of AMI-227 as an MR contrast agent for detection and
      characterization of focal hepatic lesions, with MR imaging done while the
      contrast agent is in the intravascular space (blood-pool phase). SUBJECTS AND
      METHODS: Twenty-two patients with known or suspected focal hepatic masses
      underwent T1- and T2-weighted MR imaging of the liver at 1.5 T before and
      immediately after drip infusion of AMI-227 at doses of 0.8, 1.1, or 1.7 mg Fe/kg.
      Unenhanced and contrast-enhanced images were analyzed qualitatively (lesion
      detection and tissue characterization) and quantitatively (lesion-liver contrast
      to-noise ratio). RESULTS: AMI-227 enhanced signal in normal liver and blood
      vessels on T1-weighted images and decreased signal in these tissues on T2
      weighted images. Qualitatively and quantitatively, lesion-liver contrast was
      increased for solid tumors (non-cyst and nonhemangioma) at all three doses (p <
      .02) on both T1- and T2-weighted images. Differentiation between blood vessels
      and small lesions was easier on contrast-enhanced images, which allowed increased
      confidence in excluding lesions. Unique enhancement patterns were noted for
      hemangiomas, solid tumors, and cysts. CONCLUSION: Initial clinical experience
      suggests that AMI-227 is a useful contrast agent for detection and
      characterization of focal hepatic lesions.

PMID- 7717224
TI  - Treatment of hepatocellular carcinoma: value of percutaneous microwave
      coagulation.
AB  - OBJECTIVE: Percutaneous microwave coagulation therapy (PMCT) is a new therapeutic
      technique for the treatment of solid neoplasms that uses an energy source
      different from those of other interstitial therapies. We report our initial
      experience using PMCT to treat hepatocellular carcinomas. MATERIALS AND METHODS:
      NIne hepatocellular carcinomas exceeding 3 cm in diameter in nine patients were
      treated with PMCT. Within 2 weeks before PMCT, all patients had been treated with
      transcatheter arterial embolization therapy, which had failed to produce complete
      necrosis of the tumors. PMCT was done under local anesthesia. A 14-gauge guiding
      needle was inserted percutaneously toward the lesion under sonographic guidance,
      and a needle electrode was positioned precisely within the lesion. Microwaves of
      2450 MHz in frequency were produced for 60 sec with a 60-W emission. Three to 12
      microwave emissions were administered in each case. RESULTS: Dynamic CT showed
      that unenhanced areas indicative of coagulation necrosis developed in all
      lesions. All lesions appeared smaller without enhancement: on CT, the tumor
      diameters (mean +/- SD) were 48 +/- 13 mm before treatment and 41 +/- 13 mm 1
      month after treatment. Follow-up studies showed that five lesions were controlled
      without any signs of recurrence. All patients tolerated the treatments well, and
      no serious complications occurred. CONCLUSION: Our preliminary experience
      suggests that PMCT may be a useful alternative to other forms of interstitial
      therapy for the treatment of hepatocellular carcinomas.

PMID- 7717226
TI  - Optimal contrast enhancement of the liver using helical (spiral) CT: value of
      SmartPrep.

PMID- 7717225
TI  - Percutaneous ablation therapy for hepatocellular carcinomas.

PMID- 7717227
TI  - Anatomic communications between the three retroperitoneal spaces: determination
      by CT-guided injections of contrast material in cadavers.
AB  - OBJECTIVE: A variety of retroperitoneal diseases such as pancreatitis, infection,
      and trauma may cause fluid collections in the three major retroperitoneal spaces.
      The purpose of our study was to elucidate flow patterns of fluid between the
      various compartments to assist the clinical-radiologic assessment and treatment
      of various retroperitoneal diseases. MATERIALS AND METHODS: In eight cadavers, CT
      guidance was used to selectively inject 35-1000 ml of contrast medium by hand or
      power injector into five perirenal, two posterior pararenal, and two anterior
      pararenal spaces. After the injections, CT of the entire abdomen and pelvis was
      done with 10-mm-thick sections at intervals of 10-40 mm. All images were reviewed
      in detail by a group of experienced body imagers to assess the pathways of flow
      of contrast material between the three major retroperitoneal spaces. RESULTS: The
      caudal cone of perirenal fascia was uniformly patent. A narrow channel connected
      the two perirenal spaces in the midline; the posterior border of this channel
      abutted the anterior margins of the abdominal aorta and the inferior vena cava.
      The perirenal, anterior pararenal, and posterior pararenal spaces all
      communicated with the infrarenal space, which in turn connected with the
      extraperitoneal spaces in the pelvis. When large quantities of contrast medium
      are injected in the perirenal or pararenal spaces and the infrarenal space is
      filled, the infrarenal space may then serve as a conduit across the midline of
      the abdomen. The anterior pararenal space crossed the midline and had a distinct
      retrorenal extension but no intraperitoneal connection. The slender posterior
      pararenal space had an anterolateral extension en route to the prevesical space.
      CONCLUSION: Our findings show pathways and extensions of the perirenal, anterior
      pararenal, and posterior pararenal spaces that should be considered when
      assessing a variety of retroperitoneal diseases. Perinephric collections, such as
      hematomas and urinomas, have at least a potential conduit across the midline or
      into the pelvis. Our study explains how blood from a ruptured abdominal aortic
      aneurysm may enter either perinephric space. Anterior pararenal processes, such
      as pancreatitis or appendicitis, can extend into the pelvis or cross the midline,
      and posterior pararenal blood from trauma can also flow into the pelvis.

PMID- 7717228
TI  - Why perirenal disease does not extend into the pelvis: the importance of closure
      of the cone of the renal fasciae.
AB  - OBJECTIVE: The prevailing concept is that lack of fusion of the anterior and
      posterior renal fasciae caudally (an open cone) allows free communication between
      the perirenal space and the extraperitoneal portion of the pelvis. However,
      perirenal disease rarely extends into the pelvis and an open cone has not been
      observed on CT scans. Accordingly, we determined the anatomy of the caudal extent
      of the cone of the renal fasciae in cadavers and on CT scans. MATERIALS AND
      METHODS: Anatomic dissections of the lower portion of the retroperitoneum and the
      extraperitoneal portion of the pelvis were made in eight cadavers. Two cadavers
      were intact, two had colored latex injected into the perirenal space before
      dissections, and the abdomens and pelves of four were sectioned transversely in 3
      to 5-cm-thick slices. The renal fasciae were traced on transparent films placed
      on the cross sections, and computer-generated three-dimensional representations
      of the tracings were made. These anatomic findings were correlated with
      observations made on CT scans of 59 consecutive patients with diseases involving
      the lower part of the retroperitoneum and the extraperitoneal portion of the
      pelvis (32 patients with hemorrhage, 16 with inflammatory processes, and 11 with
      neoplastic conditions). RESULTS: The anatomic study showed that the anterior and
      posterior renal fasciae merge to form a single multilaminar fascia in the iliac
      fossa. Anteriorly, this common fascia is loosely connected to the parietal
      peritoneum. Posteriorly lies the caudal continuation of the posterior pararenal
      compartment. This joins with the laterocaudal continuation of the central part of
      the retroperitoneum, which contains the iliac vessels. The distal part of the
      ureter lies within the caudal continuation of the single multilayered renal
      fascia. The CT studies done in patients showed that extension of the perirenal
      processes to the pelvis and vice versa was both restrained and uncommon: no
      direct extension of any abnormalities was observed in either direction, and
      laminar thickening of the fasciae was seen in one fifth of the patients.
      Similarly, no inferior communication of the perirenal space with the anterior or
      posterior pararenal spaces was seen. CONCLUSION: There is an anatomic barrier
      between the inferior perirenal space and the extraperitoneal pelvis formed by the
      fusion of the leaves of the renal fasciae into a single multilaminar fascia that
      acts as a barrier of disease extension. The multilaminar nature of this fascia,
      however, may also act as a filter, allowing some permeability between its layers.
      This potential interlaminar pathway is rare and is manifested as fascial
      thickening on CT scans. This laminar filter-barrier observation explains the lack
      of extension of perirenal diseases into the pelvis.

PMID- 7717229
TI  - Detection of radiographically occult ankle fractures following acute trauma:
      positive predictive value of an ankle effusion.
AB  - OBJECTIVE: The purpose of our study was to determine if the presence of an ankle
      effusion on plain radiographs after acute ankle trauma is predictive of occult
      ankle fracture when no fracture is visible on the standard radiographic series.
      SUBJECTS AND METHODS: The ankle radiographs of 1153 patients with acute ankle
      trauma were examined for fracture and for the presence and extent of anterior and
      posterior capsular distension. Patients with ankle effusions but no detectable
      fracture subsequently underwent sagittal and coronal complex-motion tomography.
      RESULTS: Eleven of 33 patients with ankle effusions and otherwise normal plain
      radiographs had occult fractures identified with tomography. The fracture sites
      were as follows: osteochondral fracture of talar dome (n = 4), neck of talus (n =
      1), medial malleolus (n = 1), anterior tibial rim (n = 1), posterior tibial rim
      (n = 1), tibial plafond (n = 1), lateral malleolus (n = 1), and anterior process
      of calcaneus (n = 1). The radiographic size of an ankle effusion was predictive
      of occult fracture. An ankle effusion measuring 13 mm or more in anterior plus
      posterior capsular distension had an 82% sensitivity and 91% specificity for
      underlying fracture in our series. The positive predictive value of an ankle
      effusion 13 mm or greater was 82%. CONCLUSION: The presence of an ankle effusion
      on plain radiographs following acute ankle trauma is suggestive of an underlying
      fracture. An ankle effusion of 13 mm or greater in total capsular distension has
      a positive predictive value of 82% for occult fracture and is a reasonable
      threshold to prompt additional imaging.

PMID- 7717230
TI  - Isolated avulsion of the posterior cruciate ligament: an uncommon dashboard
      injury.

PMID- 7717231
TI  - MR imaging of soft-tissue masses: diagnostic efficacy and value of distinguishing
      between benign and malignant lesions.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of MR imaging
      in predicting the pathologic diagnosis of soft-tissue masses, both neoplastic and
      nonneoplastic, and in distinguishing benign from malignant lesions. MATERIALS AND
      METHODS: The imaging features of 225 soft-tissue tumors (179 benign, 46
      malignant) in 222 patients were analyzed. Univariate analysis of multiple
      individual imaging features was done, along with stepwise logistic regression
      analysis of combinations of imaging features, to determine how useful these are
      for predicting malignancy or benignity. A subjective (group consensus) analysis
      of each case was done prospectively, and each tumor was placed into one of three
      diagnostic categories: (1) benign, diagnostic of a specific entity; (2)
      nonspecific, most likely benign; or (3) nonspecific, most likely malignant.
      Results were compared with the final diagnosis established by pathologic
      examination (n = 184) or imaging/clinical data (n = 41). RESULTS: By quantitative
      analysis, no single imaging feature or combination of features could reliably be
      used to distinguish benign from malignant lesions. For the subjective analysis, a
      correct and specific benign diagnosis could be made on the basis of MR imaging
      findings in 100 (44%) of the 225 tumors. For the entire cohort, the sensitivity
      was 78%, the specificity was 89%, the positive predictive value was 65%, and the
      negative predictive value was 94% for a malignant diagnosis. When the diagnostic
      benign tumors were excluded, the specificity and negative predictive value
      decreased to 76% and 86%, respectively, whereas the sensitivity and positive
      predictive value remained the same. CONCLUSION: Many benign soft-tissue masses
      can be correctly and confidently diagnosed with MR imaging. The prevalence of
      benign lesions among soft-tissue masses accounts for the relatively high
      specificity and negative predictive value that can be achieved with MR imaging
      for tissue characterization. However, the accuracy of MR imaging declines when
      these characteristic benign tumors are excluded from analysis. A significant
      percentage of malignant lesions may appear deceptively "benign" with the
      currently used criteria. For lesions whose imaging appearance is nonspecific, MR
      imaging is not reliable for distinguishing benign from malignant tumors, and
      these lesions warrant biopsy in most cases.

PMID- 7717232
TI  - Does the use of lidocaine affect the culture of percutaneous bone biopsy
      specimens obtained to diagnose osteomyelitis? An in vitro and in vivo study.
AB  - OBJECTIVE: When percutaneous bone biopsy is done by radiologists, local
      anesthetics such as lidocaine are routinely used. Although percutaneous bone
      biopsy of neoplasms is well accepted, it has been suggested that this procedure
      not be used to diagnose osteomyelitis because of a reported bactericidal effect
      of lidocaine and related drugs on certain organisms. The purposes of this study
      were to determine if lidocaine is bactericidal in vitro and to determine if it
      has an effect on the culture of bacteria in specimens obtained by percutaneous
      bone biopsy in vivo. SUBJECTS AND METHODS: The minimal inhibitory concentration
      and minimal bactericidal concentration of 1% lidocaine hydrochloride (10 mg/ml
      preserved with methylparaben) were determined in vitro for seven bacteria known
      to be frequent causes of osteomyelitis by using conventional clinical
      microbiologic methods. Percutaneous core bone biopsy for suspected osteomyelitis
      was done in 28 patients: 21 with and seven without the use of lidocaine. Sites
      sampled included vertebrae (14); calcanei, pubis, and ischia (two each); and
      intervertebral disks (eight). Six of the 21 patients who had percutaneous biopsy
      with lidocaine also had an open surgical biopsy without lidocaine. The results of
      cultures of the specimens were compared. Histologic evaluation and radiographic
      follow-up were used to identify false-negative results. RESULTS: The minimal
      inhibitory and the minimal bactericidal concentrations, respectively, of
      lidocaine (in milligrams per milliliter) were as follows: Klebsiella pneumoniae,
      5.0 and > 5.0; group B streptococci, 2.5 and 5.0; Staphylococcus aureus, > 5.0;
      and > 5.0; methicillin-resistant S. aureus, > 5.0 and > 5.0; Escherichia coli,
      2.5 and > 5.0; Pseudomonas aeruginosa, 5.0 and 5.0; Salmonella species, 5.0 and >
      5.0. We found no difference in bacterial growth and the number of false-negative
      results between patients who had biopsies with and those who had biopsies without
      lidocaine. Fifty percent of patients who had growth on cultures of specimens from
      percutaneous biopsies done with lidocaine had no growth on cultures of specimens
      from surgical biopsies done without lidocaine. This likely occurred because the
      surgical specimens were not obtained under cross-sectional imaging guidance.
      CONCLUSION: Up to a 50% mixture of lidocaine has no significant effect in vitro
      on the bacterial growth of the seven organisms that cause osteomyelitis most
      frequently, and no inhibitory effect on bacterial growth was seen in biopsies
      done with lidocaine in vivo. The inhibitory effect of lidocaine therefore occurs
      at a greater concentration than is used clinically. We conclude that lidocaine
      used for biopsy does not interfere with the diagnosis of osteomyelitis.

PMID- 7717233
TI  - Overuse syndromes and injuries involving the elbow: MR imaging findings.
AB  - Most elbow injuries result not from acute trauma but from repetitive microtrauma
      and chronic stress overload of the joint. Such "overuse" injuries may be
      difficult to diagnose clinically. Occasionally, even acute traumatic injuries may
      be occult radiographically and difficult to detect. In patients with elbow pain
      of uncertain origin, MR imaging may improve diagnostic specificity and accuracy.
      In this essay, characteristic MR imaging findings in common traumatic and overuse
      syndromes of the elbow are illustrated.

PMID- 7717234
TI  - Conspicuity of tumors of the head and neck on fat-suppressed MR images: T2
      weighted fast-spin-echo versus contrast-enhanced T1-weighted conventional spin
      echo sequences.
AB  - OBJECTIVE: The purpose of this study was to compare the conspicuity of tumors of
      the head and neck on MR images acquired with T2-weighted fat-suppressed fast-spin
      echo and contrast-enhanced T1-weighted fat-suppressed conventional spin-echo
      sequences. MATERIALS AND METHODS: The MR images of 29 patients with 36
      pathologically proved tumors of the head and neck were retrospectively analyzed.
      The conspicuity of these tumors was assessed on the T2-weighted sequence
      (4700/108 [TR/TE]) and on the contrast-enhanced T1-weighted sequence (500/16)
      with a 1.5-T system. Qualitative tumor-to-background contrast was graded
      separately against background muscle, fat, and mucosa (0 = not visualized, 1 =
      poorly visualized, 2 = fairly well visualized, 3 = well visualized), and the best
      overall sequence was noted for each tumor. Quantitative tumor-to-background
      ratios were measured for 10 of the tumors by using the same background markers.
      RESULTS: The mean overall qualitative tumor-to-background contrast grades for the
      T2-weighted sequence were tumor/muscle = 2.84, tumor/fat = 2.20, and tumor/mucosa
      = 1.23, and for the contrast-enhanced T1-weighted sequence, they were
      tumor/muscle = 2.02, tumor/fat = 1.58, and tumor/mucosa = 0.73. Overall, 86% of
      the tumors were better or equally well visualized on the T2-weighted images. The
      mean overall quantitative tumor-to-background ratios for the T2-weighted sequence
      were tumor/muscle = 7.93, tumor/fat = 3.34, and tumor/mucosa = 0.68, and for the
      contrast-enhanced T1-weighted sequence, they were tumor/muscle = 2.43, tumor/fat
      = 2.28, and tumor/mucosa = 0.85. CONCLUSION: The T2-weighted fat-suppressed fast
      spin-echo sequence offers better contrast between tumors and adjacent muscle,
      fat, and mucosa than does the contrast-enhanced T1-weighted fat-suppressed spin
      echo sequence and thus improves overall tumor conspicuity. In addition, the T2
      weighted sequence does not require IV contrast material and can be performed more
      rapidly than can the contrast-enhanced T1-weighted sequence. The contrast
      enhanced T1-weighted sequence may offer complementary information on the precise
      characterization of complex tumors and on the potential determination of tumor
      extent.

PMID- 7717235
TI  - Diagnosis of ocular involvement in Behcet's disease: value of spectral and color
      Doppler sonography.
AB  - OBJECTIVE: The purpose of this study was to determine the value of duplex and
      color Doppler sonography in the detection of ocular involvement in Behcet's
      disease. SUBJECTS AND METHODS: Duplex and color Doppler sonography was done in 21
      patients with Behcet's disease and ocular involvement and in 22 patients with
      Behcet's disease but without ocular involvement. Twenty health volunteers also
      were examined as a control group. Flow velocities in the central retinal artery,
      posterior ciliary arteries, and ophthalmic artery were measured in the patients
      with Behcet's disease. RESULTS: In patients with Behcet's disease and ocular
      involvement, peak systolic velocities in the central retinal, posterior ciliary,
      and ophthalmic arteries were 7.3 +/- 2.3, 12.8 +/- 3.1, and 35.8 +/- 7.2 cm/sec,
      respectively. In patients with Behcet's disease but without ocular involvement,
      these values were 10.0 +/- 1.9, 17.3 +/- 3.4, and 33.5 +/- 4.0 cm/sec,
      respectively. In control subjects, the respective calculated values were 12.3 +/-
      1.0, 16.5 +/- 1.6, and 35.8 +/- 4.4 cm/sec. For the central retinal and posterior
      ciliary arteries, peak systolic and diastolic velocities were significantly lower
      in patients with Behcet's disease and ocular involvement than in control subjects
      and patients with Behcet's disease but without ocular involvement (p < .001).
      Peak systolic and diastolic velocities in the central retinal artery were
      significantly lower in patients with Behcet's disease but without ocular
      involvement than in the control group (p < .001); however, no difference was
      observed for the posterior ciliary artery. Flow velocities in the ophthalmic
      artery were not significantly different among groups. CONCLUSION: These findings
      suggest that duplex and color Doppler sonography may be helpful in the diagnosis
      of ocular involvement in patients with Behcet's disease.

PMID- 7717236
TI  - Premedication with oral midazolam for voiding cystourethrography in children:
      safety and efficacy.
AB  - OBJECTIVE: Midazolam is a relatively short-acting water-soluble benzodiazepine
      that provides anxiolysis and anterograde amnesia and can be given orally with few
      adverse effects. We evaluated the benefit and safety of oral midazolam for
      sedation of young children during voiding cystourethrography or nuclear
      cystography. SUBJECTS AND METHODS: For 3.5 years, a highly selected group of 98
      children, ages 23 months to 9 years (mean, 4 years), were given oral midazolam
      0.6 mg/kg 20-30 min before cystourethrography or nuclear cystography. These
      children either had been frightened by a previous catheterization (39%) or seemed
      particularly frightened during an examination of their genitals in the office
      (61%). A control group of 25 children, similar in age to the study group, did not
      receive midazolam before cystourethrography. Parents were interviewed to assess
      their child's recollection of the procedure. Voiding dynamics were assessed by
      evaluating the postvoiding radiograph. RESULTS: Of the midazolam-treated
      patients, 60% had no recollection of the study, and 31% remembered part or all of
      the study but did not have a negative experience. No significant change in vital
      signs or oxygen saturation was observed in any child. In the control group, 24
      (96%) of 25 children remembered the cystographic examination (p < .01).
      Behavioral side effects occurred in 12% of the children receiving midazolam and
      consisted primarily of combative behavior as the medication was wearing off.
      Ninety-five percent of the parents indicated that they would want their child to
      have midazolam again if the cystography needed to be repeated. Of the children
      receiving midazolam, 76% had little or no residual urine after voiding, compared
      with 72% of the control group (no significant difference). CONCLUSION: In
      children who have been or are likely to be excessively frightened during
      cystourethrography or nuclear cystography, midazolam usually provides
      satisfactory amnesia and anxiolysis with few side effects or adverse impact on
      voiding dynamics.

PMID- 7717237
TI  - Voiding cystourethrography in boys: does the presence of the catheter obscure the
      diagnosis of posterior urethral valves?
AB  - OBJECTIVE: In voiding cystourethrography, the urethral catheter may or may not be
      left in place during voiding. The main argument for removing the catheter is that
      the diagnosis of posterior urethral valves may be missed because the catheter can
      hold open the valve, efface it, and render it invisible. However, if the catheter
      does not prevent the diagnosis of urethral disease, it is preferable to leave it
      in place. The catheter makes it possible to repeat the procedure easily if
      necessary, and using it to drain the bladder provides information about ureteric
      obstruction in the presence of vesicoureteric reflux. Accordingly, the purpose of
      this study was to determine whether leaving the urethral catheter in place
      throughout voiding cystourethrography affects the efficacy of the procedure for
      the diagnosis of posterior urethral valves. MATERIALS AND METHODS: Three
      radiologists reviewed the preoperative voiding cystourethrograms obtained in 48
      boys who ranged in age from 1 day to 10 years old (mean, 1.5 years). All patients
      had a diagnosis of posterior urethral valves made at cystoscopy, which was used
      as the gold standard. The voiding cystourethrogram was obtained with a catheter
      in place during voiding in 28 (58%) of the 48 boys, without a catheter in 17
      (35%), and with and then without a urethral catheter during the voiding phase of
      the study in three (6%). RESULTS: Posterior urethral valves were detected on 25
      (89%) of the 28 voiding cystourethrograms obtained with a urethral catheter in
      place and in 15 (88%) of the 17 voiding cystourethrograms done without a urethral
      catheter. The five children in whom posterior urethral valves had been diagnosed
      by cystoscopy but were not detected on voiding cystourethrography had no
      dilatation of the posterior urethra nor any other evidence of obstruction; these
      were possibly false-positive cystoscopic diagnoses. CONCLUSION: Our results show
      that a urethral catheter does not obscure posterior urethral valves in boys and
      need not be removed routinely during the voiding phase of voiding
      cystourethrography.

PMID- 7717238
TI  - Voiding cystourethrography in children with urinary tract infection: the
      frequency of vesicoureteric reflux is independent of the specialty of the
      physician requesting the study.
AB  - OBJECTIVE: The purpose of this study was to determine if the frequency of
      vesicoureteric reflux on voiding cystourethrography in children with a history of
      urinary tract infection varies according to the specialty of the physician
      requesting the examination. MATERIALS AND METHODS: The study included 309
      children (192 girls, 117 boys) with a history of urinary tract infection who had
      their first voiding cystourethrogram. The median age at first voiding
      cystourethrogram in boys was 12 months; in girls, it was 48 months. The reports
      of these examinations were retrospectively reviewed, and the presence of
      vesicoureteric reflux was recorded. The age and sex distribution of children
      referred for voiding cystourethrography by pediatric urologists and nephrologists
      (subspecialists) was compared with the age and sex distribution of children
      referred by pediatricians, family practitioners, and adult urologists (other
      clinicians). The rate of detection of vesicoureteric reflux was calculated
      according to age and sex. Ages studied were younger than 1 year, younger than 2
      years, 2-4 years, and 5 years or older. The frequency of vesicoureteric reflux in
      children referred by subspecialists was compared with the frequency in children
      referred by other clinicians, allowing for the age and sex of the children.
      RESULTS: The sex distribution of children referred for voiding cystourethrography
      was similar for subspecialists and other clinicians. More children younger than 2
      years old were referred by other clinicians than by subspecialists.
      Vesicoureteric reflux was found in 30% of boys and 29% of girls. The frequency of
      reflux in boys did not change with age. The frequency of reflux in girls 5 years
      or older (15%) was less than in younger girls. We found no significant difference
      between the rates of reflux in boys and girls within the age groups examined. The
      overall rate of detection of reflux in patients referred by subspecialists (30%)
      was almost the same as that in patients referred by other clinicians (29%). We
      also found no difference in the frequency of reflux in children referred by
      subspecialists compared with children referred by other clinicians after allowing
      for the age and sex of the children. CONCLUSION: In children with a history of
      urinary tract infection, the rate of detection of vesicoureteric reflux on
      voiding cystourethrography is independent of the specialty of the physician
      requesting the examination.

PMID- 7717239
TI  - CT diagnosis and localization of rupture of the bladder in children with blunt
      abdominal trauma: significance of contrast material extravasation in the pelvis.
AB  - OBJECTIVE: The purpose of this study was to determine the utility of CT performed
      with maximal bladder distension in showing extravasation of IV contrast material
      as a means of detecting and localizing bladder rupture in children after blunt
      trauma. MATERIALS AND METHODS: Seven of 1500 consecutive children who had IV
      contrast-enhanced CT of the abdomen after blunt trauma had a rupture of the
      bladder proved at surgery (five patients) or by clinical and imaging findings
      (two patients). The scanning protocol in all patients included occlusion of the
      Foley catheter if present and a 5-min delay after IV injection of contrast
      material prior to scanning the pelvis. The CT scans of all 1500 children were
      prospectively evaluated for the presence and location of extravasated contrast
      material in the pelvis. RESULTS: Extravasated IV contrast material in the pelvis
      was noted in all seven children with bladder rupture (intraperitoneal in four,
      extraperitoneal in three) and two of 1493 children without bladder rupture
      (extraperitoneal in both). Both children with contrast material extravasation who
      did not have bladder rupture had a renal injury. The location of the rupture
      (intraperitoneal or extraperitoneal) could be determined from the distribution of
      extravasated contrast material in the pelvis seen on CT scans. CONCLUSION: The
      use of a scanning delay at CT prior to imaging the pelvis showed extravasation of
      IV contrast material in all seven children with bladder rupture. Intraperitoneal
      and extraperitoneal bladder rupture could be differentiated on the basis of the
      distribution of extravasated contrast material seen on CT scans.

PMID- 7717240
TI  - Autosomal recessive polycystic kidney disease: long-term sonographic findings in
      patients surviving the neonatal period.
AB  - OBJECTIVE: We studied the sonographic findings and the changes in renal function
      seen on long-term follow-up of children who had the initial diagnosis of
      autosomal recessive polycystic kidney disease made in the neonatal period.
      MATERIALS AND METHODS: The case records and sonograms of 14 children with biopsy
      evidence of autosomal recessive polycystic kidney disease were evaluated. Nine
      children who survived the neonatal period were followed up for a mean of 13 years
      (range, 5-19 years) after diagnosis and form the basis of this study. Serial
      changes in renal size, echogenicity, and function were assessed sonographically.
      The imaging findings were compared with those described in published reports.
      RESULTS: The sonographic findings showed that five of the nine children had a
      decrease in renal size, and three had stable renal size over a minimum follow-up
      period of 5 years. Only one of the nine survivors showed progressive increase in
      renal size. All had increased cortical echogenicity and large kidneys. Three
      patients showed a subjective change in renal echogenicity over time. A change in
      the echogenic pattern to one that resembles autosomal dominant polycystic kidney
      disease was noted with no evidence of increase in size of the kidneys. None of
      the surviving children had renal stones or massively enlarged kidneys. The renal
      function of seven of the nine survivors has remained stable with creatinine
      clearance nearly normal (> 60 ml/min/1.73 m2), and there was no correlation
      between renal size and renal function. CONCLUSION: In patients with autosomal
      recessive polycystic kidney disease who survive the neonatal period, kidney size
      as seen on sonograms does not continue to increase despite the patients' linear
      growth and maintained normal renal function. Rather, a decrease in kidney size
      and change in echogenicity occurs, producing a pattern that is similar to that
      seen on sonograms of patients with autosomal dominant polycystic kidney disease
      but without the marked increase in kidney size that occurs in that entity. This
      changing cystic pattern on follow-up sonograms may be the reason that previous
      descriptions of the sonographic findings in cases of autosomal recessive
      polycystic kidney disease have varied and why a decrease in size may not herald
      deteriorating renal function.

PMID- 7717241
TI  - Diagnosis of appendiceal abscess in children with acute appendicitis: value of
      color Doppler sonography.
AB  - OBJECTIVE: We performed color Doppler imaging of the right lower quadrant in
      children with acute appendicitis to characterize the imaging findings indicative
      of appendiceal perforation and to determine the value of this technique in
      diagnosing appendiceal abscesses. SUBJECTS AND METHODS: Forty-seven children with
      surgically proven appendicitis underwent color Doppler sonography of the right
      lower quadrant as an adjunct to gray-scale sonography. At pathologic examination,
      27 patients had nonperforating appendicitis and 20 patients had perforating
      appendicitis. In the latter group, seven patients had abscesses and 10 had
      phlegmon. The color Doppler sonograms were evaluated for the presence or absence
      of appendiceal hyperemia, hyperemic periappendiceal or pelvic fluid collections,
      and hyperemic soft tissues in the right lower quadrant. RESULTS: Color Doppler
      sonography showed appendiceal hyperemia in 21 (78%) of the 27 patients with
      nonperforating appendicitis and in eight (40%) of the 20 patients with
      perforating appendicitis. The hyperemia was scattered in 14 (67%) of the 21
      patients without perforation and in six (75%) of the eight patients with
      perforation. The remaining patients with blood flow identifiable on color Doppler
      sonography had focal appendiceal hyperemia. For seven (35%) of the 20 patients
      with perforating appendicitis, color Doppler examination showed hyperemic,
      loculated periappendiceal or pelvic fluid collections, subsequently proved to be
      abscesses at surgery. No patient with nonperforating appendicitis had a
      hyperemic, loculated periappendiceal or pelvic fluid collection. Ten patients
      with perforating appendicitis displayed increased color Doppler signal in the
      adjacent right-lower-quadrant bowel loops and soft tissues, indicating phlegmon
      or peritonitis. CONCLUSION: Our results indicate that the best color Doppler
      sonographic predictors of appendiceal perforation are a hyperemic periappendiceal
      or pelvic fluid collection and periappendiceal soft-tissue hyperemia. A
      hyperemic, loculated fluid collection appears specific for the diagnosis of
      abscess.

PMID- 7717242
TI  - Color Doppler imaging of the uteroplacental circulation in the first trimester:
      value in predicting pregnancy failure or complication.
AB  - OBJECTIVE: The purpose of this study was to determine the utility of color duplex
      Doppler sonography of the uteroplacental circulation in predicting the outcome of
      first-trimester gestations. SUBJECTS AND METHODS: One hundred women with viable
      pregnancies of 7 to 12 weeks' gestational age were prospectively evaluated. Color
      Doppler imaging was used to identify the location of blood flow within the
      uteroplacental circulation, and spectral Doppler imaging was used to analyze
      waveforms obtained from the decidual spiral arteries. RESULTS: Abnormal color
      Doppler findings were associated with a significantly higher prevalence of
      complicated pregnancies. Among women with abnormal Doppler findings, 12 (43%) of
      28 pregnancies ended in miscarriage, whereas among women with normal findings
      only one (1.4%) of 72 women miscarried (p < .005). CONCLUSIONS: This study
      indicates that abnormal blood flow patterns of the early uteroplacental
      circulation are associated with an increased prevalence of pregnancy
      complications and that color Doppler imaging may be used to predict pregnancy
      outcome.

PMID- 7717243
TI  - Retrieval of intravascular foreign bodies: experience in 32 cases.
AB  - OBJECTIVE: Recent reports suggest that both the nature of intravascular foreign
      bodies and the tools available to retrieve them have changed substantially in the
      past decade. We reviewed our recent experience with percutaneous retrieval of
      intravascular foreign bodies to determine the efficacy and safety of the
      procedure using currently available devices. MATERIALS AND METHODS: Between 1990
      and 1994, we attempted retrieval of 35 intravascular foreign bodies in 32
      patients. Twelve patients (38%), including all five with intraarterial foreign
      bodies, were treated for complications of transcatheter interventional procedures
      that resulted in embolization of seven coils, four intravascular stents, an
      inferior vena cava filter, and a valvuloplasty balloon fragment. From procedure
      records, we reviewed the types of retrieval devices and methods used; the medical
      record was studied to determine the occurrence and treatment of any procedure
      related complications. RESULTS: Retrieval was successful in 31 (97%) of 32
      patients. All five intraarterial and 29 of 30 IV objects were removed. Nitinol
      goose-neck snares were used in 28 of 32 cases, but more than one retrieval system
      was required in eight cases (25%), often using grasping forceps, tip-deflecting
      wires, or stone baskets to move the foreign body into a more favorable position
      for snaring. In the single failure, the tip of a largely extravascular catheter
      fragment lay in a venous valve and could not be snared in a patient who refused
      surgery. Two of five patients with arterial foreign bodies suffered occlusive
      arterial spasm, reversible with local administration of nitroglycerine. Two large
      objects were repositioned to the femoral vein and removed by surgical cutdown. No
      other procedural complications occurred, and none of the patients required
      additional compression, transfusion, or surgical intervention. CONCLUSION: We
      conclude that use of preformed nitinol goose-neck snares facilitates retrieval of
      intravascular foreign bodies in most cases, although interventional radiologists
      must be familiar with a variety of techniques to deal with the expanding spectrum
      of foreign bodies currently encountered.

PMID- 7717244
TI  - Intravascular MR tracking catheter: preliminary experimental evaluation.
AB  - OBJECTIVE: This article reports on the preliminary evaluation of a new technique
      for guiding intravascular interventional procedures with MR imaging. Active real
      time position monitoring of catheters with MR imaging is made possible by
      incorporating a small RF coil into the tip of the catheter. The purpose of this
      study was to evaluate the practicability and localizing precision of this MR
      catheter tracking technique in vitro and in vivo in comparison with fluoroscopy.
      MATERIALS AND METHODS: Feed cables employing a 0.9-mm-diameter coaxial cable, a
      0.5-mm-diameter partially shielded coaxial cable, and a twisted pair cable
      attaching RF coils at the catheter tip to a coaxial plug at the catheter base
      were assessed. Further, miniature copper loop RF coils of two, three, and four
      turns were tested. In vitro validation of MR tracking was achieved by using a
      phantom consisting of a water-filled harvested segment of human aorta and iliac
      arteries embedded in gel. Accuracy of catheter placement was compared with MR and
      fluoroscopy. Subsequently, the MR tracking technique was evaluated in a swine
      model using a prototype 5-French MR tracking catheter. RESULTS: A fully shielded
      coaxial cable was found to be crucial for localizing the attached RF coil by
      means of the tracking technique. The number of coil turns had a lesser impact.
      Positions of the catheter tip measured with the MR technique and with fluoroscopy
      correlated well (r > .98), with a 6-mm 95% confidence interval of positional
      differences. Active real-time tracking of the coil-tipped catheters was achieved
      both in vitro and in vivo. The 5-French tracking catheter was successfully placed
      in the splenic and renal arteries of the swine. CONCLUSION: Robust in vivo
      tracking and accurate placement of catheters equipped with miniature RF coils are
      possible with MR imaging.

PMID- 7717245
TI  - Transient periprosthetic thickening after covered-stent implantation in the iliac
      artery.

PMID- 7717246
TI  - Percutaneous treatment of a traumatic aortic dissection by balloon fenestration
      and stent placement.

PMID- 7717248
TI  - Reconstructed helical CT scans: improvement in z-axis resolution compared with
      overlapped and nonoverlapped conventional CT scans.
AB  - OBJECTIVE: This in vitro study was designed to assess the z-axis resolving
      capabilities of reconstructed helical CT scans obtained with various imaging
      parameters versus those of conventional CT scans and the effect of decreasing
      slice index on the z-axis resolution of helical CT. MATERIALS AND METHODS: A z
      axis line-pair phantom was imaged using conventional nonoverlapped CT scans,
      conventional CT scans that overlapped by 50%, and helical CT scans with pitches
      of 1.0 and 1.5. All helical images were reconstructed at comparable slice indexes
      (image indexes of 2.0, 1.0, and 0.5 mm for pitch = 1.0, and image indexes of 3.0,
      1.5, and 0.75 mm for pitch = 1.5). Midline coronal and sagittal reconstructed
      images were obtained to allow standardized visualization of line pairs. The
      reconstructed images were reviewed separately by 10 radiologists. RESULTS: The
      overall z-axis resolution of reconstructed helical CT scans equaled or exceeded
      that of nonoverlapped conventional CT scans in all cases and equaled that of 50%
      overlapped conventional CT scans in 75% of cases. The 1.0-pitch helical sequences
      showed improved z-axis resolution with decreasing slice index. No statistically
      significant improvement in z-axis resolution could be determined by the observers
      for 1.5-pitch sequences with decreasing slice index. CONCLUSION: The use of
      helical CT with a pitch of 1.0 or 1.5 and an increased slice index can improve
      the z-axis resolution of reconstructed images when compared with nonoverlapped
      conventional CT and frequently equals the resolution of 50% overlapped
      conventional CT. This improvement in z-axis resolution should improve the
      appearance of reconstructed images (as used in CT angiography and three
      dimensional imaging) by reducing partial volume artifacts while affording faster
      scanning at a reduced skin-surface radiation dose.

PMID- 7717247
TI  - Hypoechoic fat: a sonographic pitfall.
AB  - Fat has classically been described as hyperechoic on sonograms because of its
      acoustic impedance relative to surrounding tissue, although certain types of fat
      in certain anatomic locations can be hypoechoic. Examples in the literature
      include hypoechoic fat in and around the kidneys as well as in ovarian neoplasms
      [1-3]. We present several cases of hypoechoic fat collections in various anatomic
      locations to illustrate the importance of its presence and to minimize the number
      of erroneous diagnoses.

PMID- 7717249
TI  - American martyrs to radiology. Mihran Krikor Kassabian (1870-1910). 1936.

PMID- 7717250
TI  - Double reading of certain examinations such as barium enemas and mammograms can
      increase sensitivity at the expense of specificity.

PMID- 7717251
TI  - Considering large-volume intravenous injections of iodinated contrast media for
      contrast-enhanced CT (head and body).

PMID- 7717252
TI  - A 26-year-old woman is referred for mammography by her gynecologist for
      evaluation of bilateral breast tenderness.

PMID- 7717253
TI  - A surgeon wishes to schedule a woman for wire localization of a nonpalpable
      breast lesion.

PMID- 7717254
TI  - When faced with a blunt abdominal trauma patient who has hematuria, how should I
      proceed with the imaging workup?

PMID- 7717255
TI  - Certain conditions have an increased incidence of Wilms' tumor.

PMID- 7717256
TI  - Making black-and-white slides of radiographs using Kodak Ektachrome film and a
      custom-made view box.

PMID- 7717257
TI  - Re: Breast disease (second series) test and syllabus.

PMID- 7717258
TI  - Re: Interval breast cancers in the screening mammography program of British
      Columbia: analysis and classification.

PMID- 7717259
TI  - Indocyanine green dye as a tissue marker for localization of nonpalpable breast
      lesions.

PMID- 7717260
TI  - Re: The upper gastrointestinal series at a crossroads.

PMID- 7717261
TI  - Control of pericatheter leakage of ascitic fluid in percutaneous biliary
      drainage.

PMID- 7717262
TI  - Necrotizing pancreatitis with intraductal gas.

PMID- 7717263
TI  - Intratesticular varicocele.

PMID- 7717264
TI  - CT of "stable" patients with suspected abdominal aortic aneurysm with leak or
      contained rupture.

PMID- 7717265
TI  - Improved swimmer's lateral projection of the cervicothoracic region.

PMID- 7717266
TI  - Unilateral volume loss of the fornix in patients with seizures caused by
      ipsilateral hippocampal sclerosis.

PMID- 7717267
TI  - Cerebral phaeohyphomycosis caused by Xylohypha bantiana: MR findings.

PMID- 7717268
TI  - Estimation of pesticide exposure to greenhouse applicators using video imaging
      and other assessment techniques.
AB  - Pesticide exposure in greenhouse applicators was measured using the video imaging
      technique to assess exposure (VITAE) along with dermal patches, air monitoring,
      and biological assessment techniques. The exposure of five males to pesticides
      during high- and low-volume application methods in commercial greenhouse
      operations was evaluated. Failure to use precautionary handling methods when
      using low-volume applications resulted in the highest level of dermal tracer
      deposition. Results demonstrated nonuniform deposition of tracer/pesticide
      mixtures on various body regions, supporting earlier work that questioned the
      assumption of uniform deposition when assessing exposure with the dermal patch
      technique. By combining the tracer with an oil-based concentrate, it remained
      uniformly suspended in the spray solution, and deposition ratios remained
      constant. Estimates of pirimicarb exposure using the VITAE method were highly
      correlated with excretion of urinary metabolites (r2 = 0.93). The immediate
      visual results provided by the VITAE system to applicators proved to be a
      powerful educational tool in helping them adopt precautionary application
      techniques. The need to employ protective operating procedures when handling
      pesticides was demonstrated, no matter how brief the exposure period.

PMID- 7717269
TI  - Variability of particle size-specific fractions of personal coal mine dust
      exposures.
AB  - This study estimated the ratio of the tracheo-bronchial dust fraction to the
      fraction collected by a respirable dust sampler for a variety of job
      classifications found in conventional, continuous, and longwall coal mining
      sections. The ratios could then be applied in epidemiologic studies to existing
      respirable dust measurements to estimate thoracic mass concentrations for
      evaluation of the relative importance of the respirable and thoracic dust
      fractions to obstructive lung disease. Data collected include particle size
      distributions from four U.S. underground coal mines using eight-stage personal
      cascade impactors. A total of 180 samples were examined by mine, occupation and
      occupations grouped by proximity to the mine face, and by mining technology.
      Several fractions--that collected by the 10-mm nylon cyclone, the American
      Conference of Governmental Industrial Hygienists respirable and thoracic
      particulate mass fractions, and the estimated alveolar and tracheo-bronchial
      deposition fractions--were estimated. These were not significantly different when
      grouped by occupation, by proximity of work to the mine face, or by the type of
      mining technology in use. Distributions from one mine varied from the others,
      perhaps because it used diesel equipment in the haulage ways, which contributed
      to the fine aerosol fractions. Results suggest that although the tracheo
      bronchial dust fraction may contribute to the development of obstructive lung
      disease, occupation-specific tracheo-bronchial dust fractions are not likely to
      produce stronger exposure-response estimates than the historically collected
      respirable dust concentrations.

PMID- 7717270
TI  - Lead, chromium, and cadmium emission factors during abrasive blasting operations
      by bridge painters.
AB  - Work space airborne concentrations of lead, chromium, and cadmium were measured
      during abrasive blasting by bridge painters for the determination of emission
      rates. The operation used compressed air to blast steel grit at steel or metal
      surfaces, removing lead-based paint. It was enclosed with plastic tarpaulins to
      prevent the release of lead- and chromium-laden dust. Consequently, workers were
      at increased risk from exposure by inhalation or ingestion. Area samples were
      collected in 13 contained work areas on a 4-leaf bridge and adjacent viaduct
      while blasting was performed. Enclosure volume and exhaust air flow rate were
      measured for each containment area. Work space airborne concentrations ranged
      from 196-31,410 micrograms/m3 for lead, 1-657 micrograms/m3 for chromium, and 1
      19 micrograms/m3 for cadmium. Mass balance models were used to calculate emission
      rates and emission factors using the measured area concentrations. Average
      emission factors on the bridge were 20,400 mg/m2 for lead, 75 mg/m2 for chromium,
      and 16 mg/m2 for cadmium; and on the viaduct were 8790 mg/m2 for lead, 568 mg/m2
      for chromium, and 2.0 mg/m2 for cadmium. These values were validated using
      estimates of total paint volume and composition on the structure and total waste
      generation. All estimates were within 50% of each other except chromium estimates
      for the bridge. The emission factors allow prediction of work space airborne
      concentrations during similar operations and are a first step in the design and
      implementation of control measures.

PMID- 7717271
TI  - Evaluation of standard and modified sampling heads for the International PBI
      Surface Air System bioaerosol samplers.
AB  - This study substituted sampling heads with smaller holes to collect small
      particles with the International PBI Surface Air System (SAS) battery-powered,
      bioaerosol air samplers, which have proved inefficient in collecting small
      airborne particles such as free bacteria (e.g., < 2 microns). An Andersen six
      stage (6-STG) sampler was used simultaneously with two SAS samplers (SAS high
      flow [SAS-HF] and Compact SAS [SAS-C]) to sample indoor air in two office
      environments. Discrepancies were observed in the flow rate results obtained using
      the manufacturer's Pitot Validation Kit (PVK). Air sampling results suggested no
      significant difference in the concentration of bacteria and fungi collected among
      the four sampling heads using either sampler model in a small sample (n = 5) at
      either site. However, with an additional 15 samples at Site B (n = 5 + 15 = 20),
      three of the four sampling heads statistically undersampled the 6-STG and the
      other sampling head. The field data were variable (geometric standard deviation
      [GSD] = 1.25-1.94 for bacteria; GSD = 1.18-3.51 for fungi), but within ranges
      previously observed. The manufacturer increased particle collection efficiency by
      decreasing the hole size; however, this increase was only noticeable after many
      replicates. The PVK may be used as an accurate flow rate measurement device with
      the SAS-HF sampler, though the Pitot tube measures only centerline velocity
      pressure. Because of the 10% decrease in flow rate resulting from the pressure
      drop across the PVK, the equation in the manufacturer's literature for
      calculation of average velocities (VAVG) provides a reasonable estimate of flow
      rate through the SAS-C sampler.

PMID- 7717272
TI  - Welding helmet airborne fume concentrations compared to personal breathing zone
      sampling.
AB  - Metal fume concentrations inside the welding helmet and in the personal breathing
      zone in 23 experimental welding exposures were studied to explore whether welding
      helmet use substantially attenuates exposure to airborne metal fume. Observations
      produced a mean ratio of inside to outside metal fume concentrations of 0.9 +/-
      S.D. 0.2 with a highly variable effect. Iron fume concentration was inversely
      correlated with this ratio, representing greater helmet-associated attenuation
      with heavier exposure (r = -0.70, p < 0.001). In contrast to previous reports,
      these data suggest that welding helmet use provides marginal and highly variable
      reductions in fume exposure and cannot substitute for standard respiratory
      protection.

PMID- 7717273
TI  - Radiation incident report concerning facial sunburn.

PMID- 7717275
TI  - Does the electrocardiographic pattern of "anteroseptal" myocardial infarction
      correlate with the anatomic location of myocardial injury?
AB  - The current electrocardiographic (ECG) definition of anteroseptal acute
      myocardial infarction (AMI) is a Q wave or QS wave > 0.03 second in leads V1 to
      V3, with or without involvement of lead V4. To verify whether there is a
      correlation between the ECG pattern of anteroseptal AMI and the location of an
      AMI, we compared ECG, echocardiographic, and cardiac catheterization findings of
      80 patients who fit the traditional definition of anteroseptal AMI. We found that
      48 of 52 patients (92%) who presented with ST elevation in leads V1 to V3 had an
      anteroapical infarct and a normal septum. The culprit narrowing was more
      frequently found (in 85% of patients) in the mid to distal left anterior
      descending artery. We conclude that there is no correlation and that the ECG
      pattern traditionally termed anteroseptal AMI should be called an anteroapical
      AMI; the term anteroseptal AMI should be defined as extensive anterior wall AMI
      associated with diffuse ST changes involving the anterior, lateral, and
      occasionally, inferior leads.

PMID- 7717274
TI  - Prognostic value of rest-redistribution tomographic thallium-201 imaging in
      ischemic cardiomyopathy.
AB  - The relation between the presence of viable myocardium by rest-redistribution
      thallium imaging and prognosis is not well defined. This study examined the
      prognostic value of rest-redistribution single-photon emission computed
      tomographic imaging with thallium-201 in patients with coronary artery disease
      (CAD) and left ventricular (LV) dysfunction. Patients were divided into 2 groups:
      group 1 patients (n = 47) were treated medically and group 2 patients (n = 38)
      underwent coronary revascularization. The 2 groups were comparable in the extent
      of CAD and in LV ejection fraction. Thallium images showed normal tracer uptake
      in 1 group 1 and 3 group 2 patients, fixed defects in 26 group 1 and 18 group 2
      patients, and both reversible and fixed defects in 20 group 1 and 17 group 2
      patients (p = NS). Based on analysis of 20 segments/patient, reversible defects
      were seen in 4 +/- 4 segments/patient in group 1 and 5 +/- 5 segments/patient in
      group 2 (p = NS). Viable myocardium (defined as normal tracer uptake, reversible
      defects, or mild fixed defects) was seen in 14 +/- 4 segments/patient in group 1
      and 15 +/- 5 segments/patient in group 2 (p = NS). During a mean follow-up of 31
      months, there were 16 group 1 (34%) and 6 group 2 (16%) deaths. The annual
      mortality rate was 13% in group 1 and 6% in group 2. Actuarial survival analysis
      showed better survival in group 2 than in group 1 (p = 0.056). Thus, viable
      myocardium in patients with CAD and LV dysfunction is associated with poor
      prognosis with medical therapy. Coronary revascularization improves prognosis.

PMID- 7717276
TI  - Effects of early rehabilitation on consumption of medical care during the first
      year after acute myocardial infarction in patients > or = 65 years of age.
AB  - A rehabilitation program that relied totally upon the primary health care system
      was created in Goteborg, Sweden, for patients > or = 65 years old with acute
      myocardial infarction. Patients from one primary health care district were
      assigned to a rehabilitation program (n = 91), while patients from a neighboring
      district constituted a control group (n = 99). The rehabilitation measures were
      initiated very early after the infarction with individual counseling in the home
      of the patient and later in the local health center, where 21% of the patients
      also joined a low-intensity exercise group. The control group was somewhat older
      and contained a greater number of women compared with the rehabilitation group,
      but size and course of infarction, complications, and previous morbidity were
      similar. To control for differences in age, a matching procedure was performed
      and 71 pairs of the same sex and age were found. During the first 3 months there
      was a significantly lower incidence of rehospitalization in the intervention
      group, regarding both percentage of patients (p < 0.04) and days of
      rehospitalization (p = 0.05). Visits to the emergency department without
      rehospitalization were also significantly lower in the intervention group (p =
      0.005). After 12 months the differences still remained, with the exception of
      days of rehospitalization. In the matched groups the same result was seen. While
      readmissions and emergency department visits generally were well justified in the
      intervention group, vague symptoms dominated among the controls.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7717277
TI  - Quantitative assessment with intracoronary ultrasound of the mechanisms of
      restenosis after percutaneous transluminal coronary angioplasty and directional
      coronary atherectomy.
AB  - The mechanisms of immediate and late changes after percutaneous transluminal
      coronary angioplasty (PTCA) and directional coronary atherectomy (DCA) were
      assessed by serial ultrasound imaging in 18 patients treated with PTCA and 16
      treated with DCA before, immediately after, and 6 months after coronary
      interventions. A reduction in plaque area was the main operative mechanism of
      DCA, explaining 66% of lumen enlargement. In the PTCA group, the increase in
      lumen area was the result of a more balanced combination of plaque reduction (52%
      of lumen increase) and increase in total lumen area (48%); p < 0.05 versus DCA.
      In the PTCA group, this last mechanism was prevalent (p < 0.05) in the lesions
      showing wall fracture or dissection after treatment and in the lesions with a
      mixed or calcific composition. In the PTCA group, concentric lesions showed a
      greater plaque compression than eccentric lesions (p < 0.02). Plaque increase was
      responsible for 92% and 32% of the late lumen loss after DCA and after PTCA,
      respectively (p < 0.05). In PTCA patients, a chronic reduction in total vessel
      area was the main operative mechanism of lumen reduction (67%) and was prevalent
      in lesions with a mixed or calcific composition. (p < 0.05).

PMID- 7717279
TI  - Correlation of cold pressor and flow-mediated brachial artery diameter responses
      with the presence of coronary artery disease.
AB  - Flow-mediated brachial and coronary artery vasoactivity are abnormal in patients
      with coronary artery disease (CAD) and cardiac risk factors. Cold pressor
      coronary artery vasoactivity is abnormal in patients with CAD, but brachial
      artery responses have not been studied. This study assesses whether cold pressor
      and flow-mediated brachial artery vasoactivity correlate independently with the
      presence of CAD. We studied 50 men (27 who were clinically normal, 23 with
      angiographically proven CAD) aged 23 to 59 years. With use of 7.5 MHz ultrasound,
      we measured brachial artery diameter and Doppler flow velocity at baseline,
      during contralateral ice water hand immersion (cold pressor), after 5 minutes of
      ipsilateral blood pressure cuff occlusion (flow-mediated), and after
      nitroglycerin administration. During cold pressor stimulation, mean brachial
      artery diameter increased 0.36 +/- 2.93% in normal subjects but decreased 2.38 +/
      3.32% in the CAD subjects (p = 0.006). Mean flow-mediated diameter increased
      9.11 +/- 6.01% and 6.58 +/- 7.50% in normal and CAD subjects, respectively (p =
      NS). Responses to sublingual nitroglycerin were the same in the 2 groups.
      Multiple stepwise regression analysis revealed that cold pressor vasoactivity was
      found to correlate with smoking status (p = 0.0002) and the presence of CAD (p =
      0.04). In the 32 nonsmokers undergoing assessment, only the presence of CAD
      correlated with cold pressor vasoactivity (p = 0.02). The associations of
      brachial artery vasoactivity with cardiac risk factors and CAD appear to be
      stimulus-dependent. Cold pressor vasoactivity correlates more closely with the
      presence of CAD than does flow-mediated vasoactivity.

PMID- 7717278
TI  - Features and outcome of no-reflow after percutaneous coronary intervention.
AB  - No-reflow is an uncommon complication that may occur after revascularization of
      patients with acute myocardial infarction, after interventions in saphenous vein
      bypass grafts, and after the use of some new interventional devices. However, the
      clinical impact of no-reflow after coronary intervention is unknown. Accordingly,
      this study examined the incidence, clinical presentation, angiographic
      characteristics, and outcome of no-reflow after percutaneous coronary
      intervention. No-reflow was defined as an acute reduction in antegrade flow (< or
      = 1, as defined by the Thrombolysis in Myocardial Infarction [TIMI] trial) not
      attributable to abrupt closure, high-grade stenosis, or spasm of the original
      target lesion. Among 10,676 coronary interventions performed between October 1988
      and June 1993, no-reflow occurred in 66 patients (0.6%). These patients were
      compared with a subgroup of 500 consecutive patients who did not exhibit no
      reflow. The incidence of no-reflow was 30 of 9,431 (0.3%) for percutaneous
      transluminal coronary angioplasty, 1 of 317 (0.3%) for excimer laser, 8 of 104
      (7.7%) for Rotablator (Heart Technologies, Bellevue, Washington), 21 of 469
      (4.5%) for extraction atherectomy, and 6 of 355 (1.7%) for directional
      atherectomy. Compared with those without no-reflow, patients with no-reflow
      experienced a 10-fold higher incidence of in-hospital death (15%) and acute
      myocardial infarction (31%). Correlates of in-hospital mortality included acute
      myocardial infarction on presentation (p = 0.006) and final flow < 3 (as defined
      by the TIMI trial) at completion of the procedure (p = 0.03).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7717280
TI  - Prevalence and prognostic significance of exercise-induced supraventricular
      tachycardia in apparently healthy volunteers.
AB  - The prevalence, characteristics, and prognostic significance of supraventricular
      tachycardia (SVT) occurring during maximal treadmill exercise testing were
      examined in 843 male and 540 female asymptomatic volunteers aged 20 to 94 years
      from the Baltimore Longitudinal Study of Aging who underwent exercise testing a
      mean of 2.3 times between 1977 and 1991. Exercise-induced SVT occurred during at
      least 1 test in 51 men (6.0%) and 34 women (6.3%), p = NS for gender. The 85
      subjects with exercise-induced SVT were significantly older than the 1,298 free
      from this arrhythmia (66.0 +/- 13.5 vs 49.7 +/- 18.0 years, respectively, p <
      0.001). The prevalence of SVT increased with age in men (p < 0.001) but not in
      women. Ninety-eight percent of the 141 discrete episodes of exercise-induced SVT
      were paroxysmal SVT, with heart rates varying from 105 to 290 beats/min (mean
      186.3 +/- 43.3); only 16% were > 10 beats in duration and only 4% of subjects
      were symptomatic. Nearly half (44%) of SVT episodes occurred at peak effort.
      Coronary risk factors, echocardiographic left atrial size (3.3 +/- 6.7 vs 3.3 +/-
      0.6 cm), and the prevalence of exercise-induced ischemic ST-segment depression
      (11% vs 13%) were similar in 85 subjects with SVT and 170 control subjects
      matched for age and sex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717281
TI  - Safety and tolerability of losartan potassium, an angiotensin II receptor
      antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and
      angiotensin-converting enzyme inhibitors for the treatment of systemic
      hypertension.
AB  - This report presents data on the safety and tolerability of losartan potassium
      (losartan), a selective antagonist of the angiotensin II AT-1 receptor, in
      approximately 2,900 hypertensive patients treated in double-blind clinical
      trials. In these studies, headache (14.1%), upper respiratory infection (6.5%),
      dizziness (14.1%), asthenia/fatigue (3.8%), and cough (3.1%) were the clinical
      adverse experiences most often reported in patients treated with losartan. These
      adverse experiences were also frequently reported in patients receiving placebo:
      17.2%, 5.6%, 2.4%, 3.9%, and 2.6%, respectively. Dry cough as an adverse event
      was reported in 8.8% of patients treated with angiotensin-converting enzyme
      inhibitors, and in 3.1% and 2.6% of patients treated with losartan or placebo,
      respectively. Only dizziness was considered "drug-related" more often in losartan
      treated (2.4%) than placebo-treated (1.3%) patients. In controlled clinical
      trials, losartan was better tolerated than other antihypertensive agents as
      determined by the incidence of patients reporting any drug-related adverse
      experiences. Rates of discontinuation due to clinical adverse experiences in
      patients who received losartan monotherapy or losartan+hydrochlorothiazide were
      2.3% and 2.8%, respectively, compared with placebo (3.7%). No laboratory adverse
      experiences were unexpected or of clinical importance. First-dose hypotension
      rarely occurred with losartan or with losartan plus hydrochlorothiazide, and
      withdrawal effects such as rebound hypertension were not observed in clinical
      trials. There were no clinically important differences in the clinical or
      laboratory safety profiles in the demographic subgroups for age, gender, or race.
      In controlled clinical trials, losartan demonstrated an excellent tolerability
      profile.

PMID- 7717282
TI  - Progression of mild untreated heart failure during six months follow-up and
      clinical and neurohumoral effects of ibopamine and digoxin as monotherapy. DIMT
      Study Group. Dutch Ibopamine Multicenter Trial.
AB  - There is increasing evidence that clinical deterioration in manifest chronic
      heart failure is related to both hemodynamic and neurohumoral factors. Only few
      data are available, however, on the progression of disease in its early stages,
      when treatment has not yet been initiated. The aim of this study was therefore to
      examine the changes in clinical and neurohumoral variables that occur over 6
      months in patients with clinically stable and untreated heart failure, and to
      evaluate the influence of drugs that may affect these variables. Accordingly, we
      studied 64 patients with heart failure who were in New York Heart Association
      functional class II (88%) and III (12%). They were randomized to double-blind
      treatment with the oral dopamine agonist ibopamine (100 mg 3 times daily; n =
      22), digoxin (0.25 mg once daily; n = 22) or placebo (n = 20). Their age (mean +/
      SD) was 60 +/- 8 years, and left ventricular ejection fraction (mean +/- SD) was
      0.33 +/- 0.08. Of the 64 patients, 56 (88%) completed the 6-month study period (p
      = NS between groups). Exercise time decreased in patients treated with placebo
      after 6 months (median -62 seconds; p < 0.05 vs baseline), but it increased with
      ibopamine (+48 seconds), and digoxin (+17 seconds; both p < 0.05 vs placebo).
      Plasma norepinephrine increased in the placebo group after 6 months (median + 31
      pg/ml, p < 0.05 vs baseline), but decreased in patients receiving active drug
      treatment (ibopamine: -24 pg/ml, digoxin: -98 pg/ml, both p < 0.05 vs placebo).
      Plasma renin and aldosterone levels were unchanged after 6 months in the placebo
      group, but digoxin therapy slightly reduced plasma renin concentration (-5
      microU/ml; p < 0.05 vs placebo).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717283
TI  - Indications for echocardiography in the diagnosis of infective endocarditis in
      children.
AB  - The role of transthoracic echocardiography as a diagnostic tool in children
      suspected of having infective endocarditis (IE) has not been defined. We
      hypothesized that echocardiography is only useful in children in whom there is
      high clinical suspicion of IE based on physical examination findings or
      persistently positive blood cultures. Echocardiographic reports and medical
      records of all inpatients (n = 133) from 1990 to 1992 who underwent
      echocardiography for suspected IE were reviewed. Fifty-nine of the 133 patients
      (44%) identified had either persistently positive blood cultures (n = 48),
      physical examination findings of IE (n = 20), or both (n = 9). The echocardiogram
      was positive in 7 of these patients (12%) and negative in all 74 patients without
      positive physical findings or positive blood cultures (p = 0.003). A new or
      changing precordial murmur, embolic phenomena, congestive heart failure,
      mechanical ventilation, and positive blood cultures were predictive of positive
      echocardiograms for IE by univariate analysis. The presence of fever, immune
      deficiency, and central lines, alone or in combination, was not predictive of a
      positive echocardiogram. In the absence of physical findings or persistently
      positive blood cultures, echocardiography is a low-yield study and is unlikely to
      aid in the diagnosis of IE in children.

PMID- 7717284
TI  - Provocation of latent left ventricular outflow tract gradients with amyl nitrite
      and exercise in hypertrophic cardiomyopathy.
AB  - Amyl nitrite may be used to provoke latent gradients in patients with
      hypertrophic cardiomyopathy (HC) without significant resting outflow tract
      gradients, but afterload reduction may not be comparable to a more physiologic
      stressor such as symptom-limited exercise testing. This study compared the
      ability of amyl nitrite and exercise testing to provoke outflow tract gradients
      in 57 patients (40 men and 17 women, mean age +/- SD 49 +/- 16 years) with HC
      (septal thickness 19 +/- 5 mm, average resting gradient 13 +/- 10 mm Hg) who
      underwent echocardiography at rest, after amyl nitrite inhalation, and after
      maximal exercise. No significant gradient (< 50 mm Hg) was induced after either
      provocation in 26 patients (46%); in 15 patients (26%), inducibility was achieved
      after both stressors, in 6 (11%) after exercise only, and in 10 (18%) after amyl
      only. Patients with amyl-induced gradients differed from those in whom gradients
      were noninducible on the basis of smaller outflow tract dimensions (p < 0.001),
      larger resting gradients (p < 0.001), and a greater prevalence of "septal bulge"
      morphology (p = 0.02). Those with exercise-induced gradients were able to attain
      a greater workload (p = 0.07), have larger resting gradients (p = 0.02), and also
      tended to have a septal bulge morphology (p < or = 0.01). Although outflow tract
      obstruction increased to similar levels after amyl nitrite (49 +/- 39 mm Hg) and
      symptom-limited exercise (47 +/- 39 mm Hg), gradients induced by exercise and
      amyl correlated poorly (r = 0.54).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717285
TI  - Dipyridamole echocardiography for diagnosis of coexistent coronary artery disease
      in hypertrophic cardiomyopathy. Echo-Persantine International Cooperative (EPIC)
      Study Group--Subproject Hypertrophic Cardiomyopathy.
AB  - The recognition of coexistent coronary artery disease (CAD) in patients with
      hypertrophic cardiomyopathy may be difficult by noninvasive testing based upon
      electrocardiographic changes or perfusion defects. Dipyridamole-stress
      echocardiography has proved a sensitive and highly specific test for noninvasive
      diagnosis of CAD in various patient subsets. To establish the feasibility,
      safety, and diagnostic accuracy of dipyridamole-stress echocardiography in
      patients with hypertrophic cardiomyopathy, we performed high-dose dipyridamole
      testing (up to 0.84 mg/kg over 10 minutes) in 88 patients with hypertrophic
      cardiomyopathy (63 men; mean age +/- SD, 46 +/- 17 years). A subset of 60
      patients was referred for coronary angiography independently of test results; CAD
      was defined as > or = 50% diameter narrowing in at least 1 major coronary vessel.
      Dipyridamole echocardiography/electrocardiography testing was completed in all
      patients, with no limiting side effects or adverse reactions. In the subgroup of
      60 patients with coronary angiography (14 with and 46 without CAD), chest pain
      occurred in 18 patients (8 with and 10 without CAD, p = NS); ST-segment
      depression > or = 2 mm from baseline in 28 (7 with and 21 without CAD, p = NS);
      and transient dyssynergy in 10 patients (10 with and none without CAD, p <
      0.0001). Assuming the transient regional dyssynergy to be the only criterion of
      positivity, the dipyridamole echocardiography test showed 71% sensitivity, 100%
      specificity, 100% positive predictive value, and 93% diagnostic accuracy for
      diagnosis of angiographically assessed CAD. We conclude that high-dose
      dipyridamole echocardiography testing may be considered a feasible and accurate
      tool for the noninvasive diagnosis of CAD in patients with hypertrophic
      cardiomyopathy.

PMID- 7717286
TI  - Exercise-induced hypertension in the arms due to impaired arterial reactivity
      after successful coarctation resection.
AB  - Exercise-induced hypertension of the arms is a well-known late complication after
      coarctation repair. Residual narrowing at the anastomosis site as well as
      abnormalities of the precoarctation arterial system may be the cause of this
      problem. Blood pressure response to exercise and flow-mediated arterial
      dilatation of the arms and legs were studied in 29 young adults after successful
      coarctectomy in childhood and compared with 13 control subjects. Peak exercise
      systolic blood pressure was significantly higher in patients than in control
      subjects: 238 versus 199 mm Hg (p = 0.007). Both groups had a positive systolic
      arm-leg gradient during exercise: 59 versus 37 mm Hg (p = 0.05). Flow-mediated
      dilatation of the brachial artery was significantly reduced in patients compared
      with that in control subjects: 4.2% (range 0% to 9.4%) versus 9.4% (range 3.7% to
      16%) (p < 0.0001). Flow-mediated dilatation of the femoral artery was similar in
      both groups. Dilatation of the brachial artery was inversely correlated to peak
      exercise systolic pressure in the study patients (r = -0.427, p = 0.02). A
      positive arm-leg exercise gradient partly represents physiologic circulatory
      adaptation to ergometry and is therefore not appropriate for evaluation of
      residual narrowing. Exercise-induced hypertension of the arms late after
      coarctation repair is caused by impaired arterial reactivity, which results from
      structural or functional abnormality, or both.

PMID- 7717287
TI  - Noninvasive assessment of myocardial contractility, preload, and afterload in
      healthy newborn infants.
AB  - Assessment of ventricular contractility in the newborn infant using standard
      echocardiographic indexes can result in error due to the unique physiologic state
      that exists in the neonatal period. It has been suggested from animal and human
      studies that maturational alterations in contractility occur with birth and
      continue throughout infancy. To further investigate these developmental changes,
      41 newborn infants aged 3 to 10 days and 37 children aged 3 to 18 years were
      evaluated with 2-dimensional and M-mode echocardiography. The rate-corrected
      velocity of circumferential fiber shortening (VCFc)-end-systolic wall stress
      (ESWS) relation was used as a load-independent estimate of contractility.
      Preload, afterload, and ventricular mass were also measured. Despite similar
      shortening fractions, the infant group had significantly higher mean VCFc and
      lower ESWS than the older age group (1.28 vs 1.08 circ/s and 30.2 vs 37.3 gm/m2,
      respectively). An inverse linear relation between VCFc and ESWS was found in both
      age groups. The y-intercept was higher in the infant group (p < 0.01), and the
      slope of the mean regression line was steeper than in the older children (p <
      0.01). Ventricular mass in relation to body surface area increased with age. We
      conclude that (1) newborn infants have a higher basal contractile state that
      cannot be accounted for by lower afterload, (2) myocardial performance is more
      sensitive to afterload in the immature heart, and (3) shortening fraction may
      underestimate ventricular function in the newborn.

PMID- 7717288
TI  - Short-term use of intravenous milrinone for heart failure.

PMID- 7717289
TI  - Preparticipation cardiovascular evaluation of the competitive athlete:
      perspectives from the 30-year Italian experience.

PMID- 7717290
TI  - Does preoperative coronary revascularization before noncardiac surgery reduce the
      risk of coronary events in patients with known coronary artery disease?

PMID- 7717291
TI  - Direct testing for low-density lipoprotein cholesterol.

PMID- 7717292
TI  - I view with alarm.

PMID- 7717293
TI  - Myocardial ischemia during sexual activity in patients with coronary artery
      disease.

PMID- 7717294
TI  - Effect of propranolol on circadian variation of myocardial ischemia in elderly
      patients with heart disease and complex ventricular arrhythmias.

PMID- 7717295
TI  - Three-year sustained benefit from enhanced external counterpulsation in chronic
      angina pectoris.

PMID- 7717296
TI  - Rapid bedside whole blood cardiospecific troponin T immunoassay for the diagnosis
      of acute myocardial infarction.

PMID- 7717297
TI  - Noninvasive evaluation of aortocoronary bypass grafts with magnetic resonance
      flow mapping.

PMID- 7717299
TI  - Enalapril-induced regression of hypertensive left ventricular hypertrophy,
      regional ischemia, and microvascular angina.

PMID- 7717298
TI  - Intracoronary diltiazem for microvascular spasm after interventional therapy.

PMID- 7717300
TI  - An intravascular ultrasound study of the influence of angiotensin-converting
      enzyme inhibitors and calcium entry blockers on the development of cardiac
      allograft vasculopathy.

PMID- 7717301
TI  - Imaging the left anterior descending coronary artery by high-frequency
      transthoracic echocardiography in heart transplant patients.

PMID- 7717302
TI  - Combination of amiodarone and flecainide.

PMID- 7717303
TI  - HMG-CoA reductase inhibitors, gemfibrozil, and myopathy.

PMID- 7717304
TI  - Putting patients first.

PMID- 7717305
TI  - Hepatic encephalopathy after portosystemic shunts: any clues from tips?

PMID- 7717306
TI  - TIPS: the immediate problems solved.

PMID- 7717307
TI  - Small bowel manometry.

PMID- 7717308
TI  - Primary intrahepatic stones.
AB  - Hepatolithiasis, or primary intrahepatic stones, is prevalent in the Far East.
      This clinical syndrome has been previously referred to in the West as Oriental
      cholangiohepatitis. The majority of primary intrahepatic stones are calcium
      bilirubinate stones, but intrahepatic stones with high cholesterol purity have
      recently been recognized. Primary intrahepatic stones are formed de novo within
      the liver and can be distinguished from extrahepatic stones on the basis of a
      unique pathogenetic etiology, chemical composition, and clinical course. Patients
      with hepatolithiasis are often plagued by a progressive illness punctuated by
      multiple intrahepatic strictures, recurrent cholangitis, liver abscesses, and
      hepatic destruction. Advances in interventional radiological techniques,
      cholangioscopy, and novel surgical innovations have led to significant changes in
      the way these patients are now managed.

PMID- 7717310
TI  - Transjugular intrahepatic portosystemic shunting: decreased survival for patients
      with high APACHE II scores.
AB  - OBJECTIVES: To determine which clinical characteristics are associated with
      decreased survival after transjugular intrahepatic portosystemic shunting (TIPS).
      METHODS: Forty-nine consecutive patients were treated with TIPS; 46 of them had
      refractory variceal bleeding. Univariate statistics and logistic regression
      analyses were used to determine the relationship between clinical, biochemical,
      and hemodynamic variables and 30-day) survival. RESULTS: Shunt insertion was
      successful in 48 (98.0%) of 49 cases. Median portal-systemic gradient was reduced
      from 22.5 (range 9-36) [median (5th-95th percentile)] to 12 (range 4-20) mm Hg.
      Thirty (61.2%) of 49 patients survived more than 30 days; four patients died more
      than 30 days after TIPS in mean follow-up of 8.4 months. Significant differences
      (p < 0.05) were found between those who survived more than 30 days and those who
      did not, with respect to preprocedural prothrombin time, bilirubin, albumin,
      alanine aminotransferase, and treatment with vasopressin and nitrates, balloon
      tamponade, or mechanical ventilation. Whereas there were no significant
      differences between the pre- and post-TIPS portal vein pressures and portal
      systemic gradients in survivors and non-survivors, the pre- and post-TIPS hepatic
      vein pressures were significantly lower in survivors. Survival was inversely
      proportional to Child-Pugh class (p < 0.01) and to APACHE II score (p < 0.01).
      The single determinant most closely associated with decreased survival in the
      month after TIPS was the APACHE II score, a score of 18 stratifying patients into
      those at low and high risk of mortality [odds ratio 21.7 (CI 3.6-131.7)]. Only 1
      (7.7%) of 13 patients with Child-Pugh C cirrhosis and an APACHE II score
      exceeding 18 survived more than 30 days. CONCLUSIONS: Patients with advanced
      cirrhosis, especially those with high pre-TIPS APACHE II scores, are at high risk
      for reduced survival after TIPS, despite adequate portal decompression.

PMID- 7717309
TI  - Hepatic encephalopathy after transjugular intrahepatic portosystemic shunts:
      incidence and risk factors.
AB  - OBJECTIVES: The aim of this study was to determine the incidence of new or
      worsened hepatic encephalopathy after transjugular intrahepatic portosystemic
      shunts (TIPS) and to ascertain which clinical characteristics are associated with
      this complication. METHODS: At the University of California, San Francisco, over
      22 months, TIPS were placed successfully in 108 adults. Seventy-seven patients in
      whom it was possible to assess the development of encephalopathy comprised the
      study population. Clinically significant encephalopathy was assessed at protocol
      clinic follow-up and, in some cases, by phone contact with the patient and the
      referring physician. Post-TIPS encephalopathy was defined as new onset of
      clinical encephalopathy requiring treatment or worsening of preexisting
      encephalopathy within 1 yr of TIPS. RESULTS: The overall incidence of new or
      worsened encephalopathy was 23% (18/77). Post-TIPS encephalopathy was well
      controlled with lactulose in 78% of cases and was progressive in 22%.
      Multivariate analysis showed that an increased risk of encephalopathy was
      associated with an etiology of liver disease other than alcohol [relative risk
      (RR) 9.2, p = 0.0052], female gender (RR 3.0, p = 0.029), and hypoalbuminemia (RR
      2.2 for each 1 g/dl decrease, p = 0.044). CONCLUSIONS: Hepatic encephalopathy is
      a common complication of TIPS that can be controlled medically in most patients.
      The identification of clinical variables associated with an increased risk of
      encephalopathy may be useful in the selection of appropriate candidates for this
      procedure.

PMID- 7717311
TI  - Prevalence and natural history of colonic angiodysplasia among healthy
      asymptomatic people.
AB  - OBJECTIVE: The prevalence of colonic angiodysplasia (AD) among healthy
      asymptomatic people is unknown, and the natural history of these lesions has not
      been clearly defined. The purpose of our study was to determine prevalence and to
      review and assess the natural history of AD. METHODS: Each of the authors had
      previously published his own prospective study that involved screening
      colonoscopy for the detection of neoplasia in asymptomatic adult men and women
      who had never bled. All pathological lesions diagnosed by endoscopy were
      recorded, but only data pertaining to polyps were published. We pooled and
      analyzed the endoscopic findings (raw data) from those studies and assessed the
      natural history of the lesions by reviewing the medical charts of affected
      subjects to determine whether bleeding had occurred. Nine hundred sixty-four
      patients were evaluated (mean age, 62 yr). All were > or = 50 yr old (range, 50
      79 yr), not anemic, Hemoccult negative, asymptomatic, and had full colonoscopy to
      the cecum. RESULTS: Eight subjects had AD (prevalence, 0.83%). Lesions in
      affected individuals were usually small (mean size, 4.0 mm) and most often were
      located in the right colon (62%). No subject bled, and all maintained a stable
      hemoglobin (mean, 14.6 g%) with a mean follow-up of 3 yr. CONCLUSIONS: We
      conclude that 1) colonic AD is uncommon among healthy asymptomatic people
      (prevalence, 0.83%), 2) lesions are usually small (< 10 mm) and are located
      proximal to the hepatic flexure, 3) the natural history for AD in these people is
      benign, and the risk of bleeding over a 3-yr period is low (0% in 3 yr), and 4)
      because of this low risk, endoscopic treatment for incidental (nonbleeding) AD is
      unnecessary.

PMID- 7717312
TI  - Analysis of 3,294 cases of upper gastrointestinal bleeding in military medical
      facilities.
AB  - OBJECTIVES: Upper gastrointestinal bleeding (UGIB) remains a commonly encountered
      medical emergency with significant morbidity and mortality. Most large studies
      detailing the specific incidence, demographic, and mortality data were performed
      more than a decade ago. This study analyzes 3,294 cases of UGIB from 139 military
      medical treatment facilities over a 12-month period. METHODS: A retrospective
      chart review of Department of Defense military medical treatment facilities for
      UGIB was performed from October 1990 through September 1991. Core data such as
      demographic information were analyzed, as well as specific data relating to UGIB.
      RESULTS: The incidence of UGIB was 36 per 100,000 population with a male-to
      female ratio of 2.18 and a mean age of 52 +/- 19.65 yr. The number of cases
      increased with age; 44.5% of all patients were > or = 60 yr old. The overall
      mortality was 7.0% (231 of 3294), and death rates were similar among males and
      females (7.1% vs. 6.8%) with an odds ratio of 1.03 (CI: 0.77-1.402). Mortality
      increased with age in both genders; 73.2% of deaths occurred in patients more
      than 60 yr old. Comorbid illness was noted in 50.9% (1675 of 3294) of patients,
      with similar occurrence in males (48.7%) and females (55.4%). One or more
      comorbid illnesses were noted in 98.3% of the patients who died, and in 72.3% of
      cases, they were the primary cause of death. Bleeding was the primary cause of
      death in 18.6% of patients. Upper endoscopy was performed in 68.8% of cases,
      therapeutic endoscopy in 12.6%, repeat endoscopy in 10.7%, and surgery in 4.4%.
      Blood transfusions were administered in 47.3% of cases, with most patients
      receiving < 5 units of blood. Rebleeding after initial hemostasis was noted in
      7.1% of cases. Factors related to increased mortality include age > 60 (p <
      0.001), transfusion requirement > 5 U (p < 0.001), presence of comorbid illness
      (p < 0.001), rebleeding after initial hemostasis (p < 0.005), surgery (p <
      0.001), and UGIB occurring during hospitalization (p = 0.027). CONCLUSIONS: We
      conclude: 1) The incidence of UGIB is 2-fold greater in males than in females, in
      all age groups; however, the death rate is similar in both sexes. 2) The
      mortality rate in this study is slightly lower than in most previous studies and
      may be more reflective of the average mortality in the community at large. 3) In
      UGIB patients, comorbid illness and not actual bleeding is the major cause of
      death. 4) Upper endoscopy was performed less often in this study than in other
      studies, and there were fewer blood transfusions; however, rebleeding and
      mortality rates remained similar.

PMID- 7717313
TI  - Anal wall thickness under normal and inflammatory conditions of the anorectum as
      determined by endoluminal ultrasonography.
AB  - OBJECTIVES: To determine the normal dimensions of the anal wall and if there were
      detectable differences in inflammatory disorders. METHODS: A cross-sectional
      survey was performed on all patients referred to a university anorectal
      ultrasound clinic who had either perianal Crohn's disease (17 patients), ileoanal
      pouches (15 patients), perianal fistula (15 patients), or previous radiation to
      the rectum (5 patients). Results were compared to 40 normal controls. Anal wall
      thickness (AWT), mucosa, submucosa, internal sphincter thickness (MSIT), and
      external sphincter thickness (EST) were measured or calculated. Intra- and
      interobserver reliability was assessed. RESULTS: The mean AWT was 14.8 mm (95%
      CI: 14.0-15.6), mean EST was 8.3 mm (95% CI: 7.6-9.0), and the mean MSIT was 6.5
      mm (95% CI: 5.8-7.2) in the control subjects. Measurements did not differ
      significantly with sex or with an increase in age. Patients with perianal Crohn's
      disease, ileoanal pouches with septic complications, and previous local
      radiotherapy had significant increases in anal wall thickness. In Crohn's
      disease, the significant increase was in MSIT, whereas, in the pouch patients,
      the increase was in the EST. Reliability studies demonstrated a learning curve
      with experience and a better correlation with determination of AWT than MSIT.
      CONCLUSIONS: Patients with anorectal inflammatory conditions have increased
      thickness in anal wall dimensions.

PMID- 7717314
TI  - Rectal blood flow in ulcerative colitis.
AB  - OBJECTIVE: To determine the state of local blood flow in ulcerative colitis.
      METHODS: Rectal blood flow was measured by means of laser Doppler flowmetry
      during endoscopy in 20 patients with active or inactive ulcerative colitis and in
      20 healthy controls. RESULTS: A significant (p < 0.01) reduction in the values of
      rectal perfusion was observed in ulcerative colitis patients both in active phase
      and in clinical and endoscopic remission. CONCLUSIONS: Impaired local blood flow
      may have a pathogenetic role in ulcerative colitis. Remission of the disease is
      not accompanied by normalization of local microcirculation, which may predispose
      to relapses.

PMID- 7717315
TI  - Gastrointestinal blood loss with low dose (325 mg) plain and enteric-coated
      aspirin administration.
AB  - OBJECTIVES: The purpose of this study was to assess gastrointestinal blood loss
      with low dose (325 mg) plain and enteric-coated aspirin. METHODS: A total of 47
      healthy volunteers participated in randomized, controlled acute and chronic
      trials. Seventeen participated in a repeated measures acute trial, and 30
      participated in an independent sample chronic trial. Gastrointestinal blood loss
      was determined by obtaining 72-hour stool collections and quantitating Chromium
      51 labeled erythrocytes. RESULTS: Acute phase trials: gastrointestinal blood loss
      during base line was 0.47 (+/- 0.11) mL/day, 0.96 (+/- 0.12) mL/day with enteric
      coated aspirin (p < 0.0006), and 1.82 (+/- 0.35) mL/day with plain aspirin (p <
      0.0001 vs. base line, p = 0.0476 vs. enteric-coated aspirin). Chronic phase
      trials: gastrointestinal blood loss was 1.12 (+/- 0.31) mL/day with enteric
      coated aspirin (p = 0.0024 vs. control) and 2.60 (+/- 0.68) with plain aspirin (p
      < 0.0001 vs. control, p = 0.0364 vs. enteric-coated aspirin). CONCLUSIONS: During
      acute and chronic ingestion, plain aspirin at a dose of 325 mg/day significantly
      increased gastrointestinal blood loss when compared to control or enteric-coated
      aspirin values, although enteric-coated aspirin values were also significantly
      increased compared to control. Gastric adaptation does not decrease blood loss
      with low dose aspirin consumption.

PMID- 7717316
TI  - Common bile duct sphincter of Oddi stenting in patients with suspected sphincter
      dysfunction.
AB  - OBJECTIVES: Some patients seem to have symptoms or other findings that imply that
      they have sphincter of Oddi dysfunction, but when the sphincter pressure is
      measured, the basal resting pressure is not greater than 40 mm Hg. Because
      empiric sphincterotomy can alleviate some of these patients'symptoms, it is
      suspected that they have intermittent spasm or dysfunction. Prolonged stenting of
      the sphincter would prevent symptoms in patients with this intermittent disorder.
      Thus, one could determine which patients would benefit from a sphincterotomy
      without subjecting all the patients to the risk of sphincterotomy. METHODS:
      Twenty-one patients with suspected sphincter of Oddi dysfunction were studied.
      All had basal sphincter of Oddi pressures < 40 mm Hg. The gallbladder was in situ
      in three. The others had persistent abdominal pain after cholecystectomy. Benefit
      was defined as no symptoms for 2 months after stent placement, followed by
      continued lack of symptoms once a sphincterotomy was performed. RESULTS: Nine
      patients benefited and 12 did not. One relapsed, but benefited from a repeat
      sphincterotomy. Eight patients (38%) met criteria for pancreatitis after stent
      placement. Two had severe pancreatitis with pseudocyst development. There were no
      sphincterotomy-related complications. CONCLUSIONS: The results suggest that
      patients without basal resting sphincter of Oddi pressure criteria may have
      intermittent spasm or dysfunction which can be deduced by achieving benefit after
      stenting, but the risk of pancreatitis from this technique as described is too
      high to recommend stenting as a routine method for detecting patients with
      intermittent sphincter dysfunction/spasm. Alternate methods need to be developed
      to identify these patients.

PMID- 7717317
TI  - Flow cytometric DNA analysis of ulcerative colitis using paraffin-embedded biopsy
      specimens: comparison with morphology and DNA analysis of fresh samples.
AB  - OBJECTIVES: The detection of aneuploidy in colonic mucosa by flow cytometric DNA
      analysis has been advocated as an indicator of high risk for ulcerative colitis
      (UC) patients developing colon carcinoma. To date, studies have primarily
      utilized fresh tissue and have had two limitations: a significant number of
      possible false-positive findings (aneuploidy in the absence of detectable
      dysplasia) that may be due to DNA degradation, and the inherent inability to
      perform retrospective studies. The latter has compromised the adequate assessment
      of flow cytometric DNA analysis for its clinical utility in UC patients. Our
      objective was to attempt to overcome the limitations that have been present in
      DNA analysis by flow cytometry. METHODS: After having established, in our
      laboratory, an optimal method that allowed reliable DNA analysis on paraffin
      embedded mucosal biopsy specimens, we conducted three separate studies to address
      the above problems associated with DNA analysis with fresh colonic samples: 1)
      comparison of DNA analysis between fresh and paraffin-embedded colonic mucosal
      samples from UC patients without dysplasia, 2) correlation between morphology and
      DNA ploidy on paraffin-embedded tissues showing no dysplasia and various degrees
      of dysplasia, and 3) sequential analysis of fresh, normal colonic mucosal samples
      to further evaluate possible causes of false aneuploidy. RESULTS: We observed 1)
      that there is discordance in DNA ploidy between paraffin-embedded and fresh
      samples showing no dysplasia in that aneuploidy was found in 33/46 (72%) of fresh
      samples, whereas 3/40 (7.5%) were aneuploid by biopsies from the corresponding
      anatomic sites. 2) There is excellent correlation between dysplasia and DNA
      ploidy results with paraffin-embedded tissue, i.e., none of 16 samples negative
      for dysplasia, none of seven samples indefinite for dysplasia, and seven of eight
      samples positive for dysplasia were aneuploid. 3) DNA degradation produced a
      spurious, near-diploid aneuploid peak in a normal colonic mucosal sample when it
      was left in saline more than 1 hr before analysis. CONCLUSIONS: The above
      described results demonstrate that performing flow cytometric DNA analysis with
      formalin-fixed paraffin-embedded biopsy samples is feasible and that this
      technique may provide more reliable ploidy results than does the use of fresh
      samples, when rapid refrigeration and/or freezing of the fresh samples cannot be
      accomplished consistently, and will permit retrospective DNA ploidy studies
      assessing risk of cancer in UC patients.

PMID- 7717318
TI  - Proliferative activity in colonic adenomas as a predictor of metachronous
      adenomas as assessed by proliferating cell nuclear antigen immunohistochemistry.
AB  - OBJECTIVES: The aim of this study was to determine whether cell proliferation in
      colonic adenomas, as estimated by proliferating cell nuclear antigen (PCNA),
      predicts the development of metachronous colonic adenomas. METHODS: Forty
      patients who underwent prior endoscopic polypectomy for colonic adenomas were
      reevaluated by colonoscopy 2 yr later. The expression of PCNA was studied in all
      adenomas that were removed. A five-point semiquantitative scale of 1-5 was used
      to estimate the PCNA score by the percentage of positively stained cells.
      RESULTS: Among the 40 patients studied, 16 developed recurrent adenomas (group A)
      and 24 were free of adenomas (group B). At initial colonoscopy, a total number of
      51 adenomas (25 in group A and 26 in group B), were found. The median PCNA score
      in group A and group B index adenomas was 4 (interquartile range, 3-5) and 2
      (interquartile range, 1-3), respectively (p < 0.01, Mann-Whitney U-test). A
      stepwise logistic regression analysis showed that PCNA score is a significant
      risk factor (p = 0.007, odds ratio 15.8, 95% confidence interval 2.2-112.4) in
      predicting adenoma recurrence. The median PCNA score in metachronous adenomas was
      2 (interquartile range, 1-3). The difference in the PCNA score between group A
      index and metachronous adenomas was again statistically significant (p < 0.01,
      Mann-Whitney U-test). CONCLUSIONS: We conclude that the increased expression of
      PCNA in colonic adenomas may be a predictor for metachronous adenomas.

PMID- 7717319
TI  - Possibility of postprandial electrogastrography for evaluating vagal/nonvagal
      cholinergic activity in humans, through simultaneous analysis of postprandial
      heart rate variability and serum immunoreactive hormone levels.
AB  - OBJECTIVES: To investigate changes in postprandial electrogastrography (EGG) from
      the neurohormonal mechanisms. METHODS: We measured EGG indices [frequency
      amplitude of normal 3-cpm (EGG-3 cpm)], high frequency amplitude of heart rate
      variability which has reflected cardiac parasympathetic tone, and several serum
      immunoreactive (ir)-hormone levels in 12 fasted male volunteers (mean age 25.3
      yr). RESULTS: Immediately after the liquid food intake (250 kcal), a transient
      decrease in EGG-3 cpm frequency (from 0.045 +/- 0.001 Hz to 0.040 +/- 0.001 Hz; p
      < 0.05) accompanied by an increase in high frequency amplitude (from 31.05 +/-
      3.45 ms to 39.10 +/- 4.08 ms; p < 0.05), and a serum immunoreactive gastrin level
      increase (from 38.72 +/- 4.92 pmol/L to 54.00 +/- 10.45 pmol/L; p < 0.05) and an
      immunoreactive somatostatin level decrease (from 15.00 +/- 0.43 pmol/L to 13.70
      +/- 0.46 pmol/L; p < 0.01) were observed, suggesting vagal excitement. EGG-3 cpm
      amplitude and serum immunoreactive human pancreatic polypeptide (hPP) levels
      significantly increased soon after ingestion, and these changes lasted for 30
      min. Furthermore, there was a positive correlation between changes in EGG-3 cpm
      amplitude and those in serum immunoreactive hPP levels during the postprandial
      periods (r = 0.55, p < 0.001). CONCLUSIONS: Considering the reports that a
      cholinergic, nonvagal pathway is of major importance in food-stimulated hPP
      release, the present results suggest that postprandial changes in EGG-3 cpm
      frequency and amplitude might be a good tool for evaluating not only vagal but
      also nonvagal cholinergic activity in the human gut.

PMID- 7717320
TI  - A novel therapy for internal hemorrhoids: ligation of the hemorrhoidal artery
      with a newly devised instrument (Moricorn) in conjunction with a Doppler
      flowmeter.
AB  - OBJECTIVES: To assess the usefulness of hemorrhoidal artery ligation (HAL) for
      internal hemorrhoids with a newly devised instrument (the Moricorn). METHODS: We
      devised a new instrument (the Moricorn) that is used in conjunction with a
      Doppler flowmeter. This instrument allows for easy and safe ligation of the
      hemorrhoidal artery. HAL with the Moricorn was performed on 116 patients with
      internal hemorrhoids who had episodes of anal pain, bleeding, and prolapse. One
      month after treatment, the effect was evaluated on the basis of improvement of
      symptoms and the shrinkage of hemorrhoidal tissue. RESULTS: The treatment's
      effect was observed in 50 of 52 patients (96%) with pain, 50 of 64 (78%) with
      prolapse, and 92 of 96 (95%) with bleeding. No patient required anesthesia
      throughout the entire procedure. No major complications were encountered with
      this treatment. CONCLUSIONS: HAL with the Moricorn is a simple, safe, and
      effective method. However, further observations predicated on a longer follow-up,
      a larger number of patients, and comparisons with other conventional treatments
      are called for.

PMID- 7717321
TI  - Mucosal synthesis and release of prostaglandin E2 from activated eosinophils and
      macrophages in ulcerative colitis.
AB  - OBJECTIVE: To study the synthesis and release of prostaglandin E2 (PGE2) in
      diseased and healthy areas of the colon in ulcerative colitis/proctitis (UC)
      patients. METHODS: Perfusate fluid from rectal and sigmoid segments in patients
      with UC was analyzed for PGE2, eosinophil cationic protein, myeloperoxidase, and
      tumor necrosis factor-alpha concentrations. To further elucidate the cell
      specific origin of mucosal PGE2 synthesis, double immunofluorescence staining as
      well as imaging analysis using antibodies reactive with prostaglandin H-synthase
      and cell-specific antigens were used on surgical colonic specimens from patients
      with active UC and from controls. RESULTS: The concentrations of PGE2 were, on
      average, 10-fold higher in perfusates from diseased areas in patients with UC
      than in perfusates from healthy areas in patients and controls. The PGE2 values
      correlated well with the released concentrations of eosinophil cationic protein,
      myeloperoxidase, and tumor necrosis factor-alpha. In the tissue specimens, there
      was a prominent colocalization in the expression of prostaglandin H-synthase on
      the one hand and CD 68 (a macrophage marker) and EG1/EG2 (eosinophil cationic
      protein markers) on the other hand, in both UC patients and controls. This did
      not apply to prostaglandin H-synthase and antibodies against B and T lymphocytes,
      neutrophils, or epithelial cells. CONCLUSION: The increased PGE2 production found
      in the inflamed mucosa in active UC may be caused by a fraction of activated
      eosinophils and macrophages.

PMID- 7717323
TI  - Large bloody ascites in association with pelvic endometriosis: case report and
      literature review.
AB  - Endometriosis is only rarely the cause of massive bloody ascites. This entity
      simulates gynecological malignancy and is seldom recognized before surgical
      exploration of the abdomen. It is more commonly seen in black nulliparous
      females. Hormonal modulation has obviated the need for surgical resection, in
      some cases. We report a case of such an entity and review the medical literature.

PMID- 7717322
TI  - Cholecystokinin-stimulated monocytes produce inflammatory cytokines and
      eicosanoids.
AB  - OBJECTIVES: Plasma cholecystokinin increases with enteral feeding.
      Cholecystokinin increases intracellular calcium in lymphocytes/monocytes and is a
      lymphocyte co-mitogen. We hypothesize that decreased cholecystokinin production
      with "bowel rest" and parenteral nutrition may be beneficial in inflammatory
      bowel disease by down-regulating gut immune/inflammatory mechanisms. The majority
      of cells observed in mucosa of inflammatory bowel disease are monocytes and
      neutrophils. Cholecystokinin effect was therefore measured on monocyte production
      of proinflammatory mediators (tumor necrosis factor alpha, interleukin-1 beta,
      interleukin-6) and neutrophil chemotaxins/activators (interleukin-8, granulocyte
      macrophage colony stimulating factor, and leukotriene B4). METHODS: Peripheral
      blood monocytes (0.5 x 10(6)) from healthy donors in 1 mL of RPMI 1640 plus 5%
      fetal calf serum were cultured for 24 h in 5% CO2 at 37 degrees C with 5
      micrograms/mL endotoxin, 1 x 10(-7) M cholecystokinin, or no agonist.
      Supernatants were analyzed by ELISA for cytokines and leukotriene B4. RESULTS:
      Endotoxin-stimulated monocytes produced 1130 pg/mL tumor necrosis factor versus
      81 pg/mL for cholecystokinin, 612 pg/mL interleukin-1 versus 10 pg/mL, 694 pg/mL
      interleukin-6 versus 30 pg/mL, 4531 pg/mL of interleukin-8 versus 3848 pg/mL, 21
      pg/mL granulocyte-macrophage colony stimulating factor versus 9 pg/mL, and 21
      pg/mL leukotriene B4 versus 12 pg/mL. Controls produced no cytokines/eicosanoids
      (N = 8, p < 0.001). CONCLUSION: Cholecystokinin increase with enteral feeding may
      up-regulate gut immune response. Cholecystokinin suppression with parenteral
      alimentation may decrease inflammatory mediator production.

PMID- 7717324
TI  - Chronic lymphocytic leukemia: an unusual cause of upper gastrointestinal
      hemorrhage.
AB  - In contrast to the acute leukemias, chronic lymphocytic leukemia (CLL) is a
      hematological malignancy with a generally good prognosis. Gastrointestinal (GI)
      involvement with CLL is unusual, and GI complications generally occur after
      malignant transformation to diffuse large cell lymphoma (Richter's syndrome). We
      present a case of CLL directly infiltrating the gastro-esophageal junction
      resulting in upper GI hemorrhage. This is only the second such case in the
      literature. We emphasize the consideration of direct leukemic infiltration in
      addition to Richter's syndrome in the differential diagnosis of GI bleeding in
      patients with CLL. Whereas the prognosis of Richter's syndrome is poor, CLL
      involvement of the GI tract may respond to treatment with chemo- or radiotherapy.

PMID- 7717325
TI  - Bouveret's syndrome.

PMID- 7717326
TI  - Colonic involvement in acute pancreatitis.

PMID- 7717327
TI  - Duodenal carcinoid tumor: endosonographic imaging and endoscopic resection.
AB  - A 75-yr-old Japanese woman was shown by endoscopy to have a sessile polyp in the
      duodenal bulb. Endoscopic biopsy confirmed the diagnosis of carcinoid tumor. The
      endoscopic ultrasound probe showed a 6-mm hypoechoic tumor that was confined to
      the submucosal layer; the underlying muscularis propria layer was intact. On the
      basis of these findings, endoscopic resection was chosen, and the tumor was
      completely resected by the strip biopsy technique with prior hypertonic saline
      and epinephrine injection; there were no complications.

PMID- 7717328
TI  - Treatment of diarrhea in carcinoid syndrome with ondansetron, tropisetron, and
      clonidine.
AB  - A 69-yr-old man with known carcinoid syndrome treated with octreotide and
      interferon-alpha 2b developed diarrhea, with six to eight watery to semiliquid
      stools per day. Diminished stool frequency and increased stool consistency were
      obtained by treatment with the 5-hydroxytryptamine-3 receptor antagonists
      ondansetron and tropisetron. Successful alleviation of the diarrhea was also
      observed with the alpha 2-receptor agonist clonidine. These observations indicate
      that these classes of drugs should be evaluated in a controlled trial in patients
      with carcinoid-associated diarrhea.

PMID- 7717329
TI  - Primary leiomyosarcoma of the liver mimicking liver abscess.
AB  - Primary hepatic leiomyosarcoma is a rare tumor, with fewer than 60 previously
      reported cases. The usual clinical presentation is painful hepatomegaly or a
      painful epigastric mass. We present the case of a 64-yr-old white man who
      presented with fevers, drenching night sweats, fatigue, leukocytosis, an elevated
      erythrocyte sedimentation rate, and an indistinct mass in the right lobe of his
      liver on CT scan. Although the clinical presentation was suggestive of hepatic
      abscess, a percutaneous biopsy was consistent with a smooth muscle tumor.
      Successful right hepatic lobectomy resulted in resolution of all the associated
      symptoms and signs. A review of the world literature produced 44 papers reporting
      a total of 54 cases. The male:female ratio was 25:26; mean age was 53.6 yr. The
      tumor tended to occur at an earlier age in women, with a group mean age of 49.0
      yr compared with 58.4 for men. It was more common in the right lobe. Metastatic
      disease was present in 40.9% of patients. The outcomes for various therapeutic
      approaches were compared. Patients treated with comfort measures alone had a mean
      survival or follow-up of 0.87 yr. The best outcome seemed to be in those patients
      treated with a combination of surgery and chemotherapy, with a mean survival or
      follow-up of 3.3 yr.

PMID- 7717330
TI  - The heterogeneity of microsatellite instability in multiple gastric cancers.
AB  - To obtain a better understanding of the role of genetic instability in developing
      gastric cancer, it is of great interest to examine microsatellite alterations in
      synchronous multiple gastric cancers that are thought may have the same genetic
      background and the same microenvironment of the stomach. We report our experience
      with two patients with synchronous multiple gastric cancers; patient 1 showed two
      carcinomas in the stomach, whereas patient 2 showed two carcinomas and two
      adenomas in the stomach. We examined the DNAs from the two cases for
      microsatellite instability and expected that the status of microsatellite
      instability in each tumor from the same stomach would be the same. However,
      patient 2 revealed heterogeneity in the microsatellite instability, i.e., an
      early cancer that showed some apparent alterations, whereas the other advanced
      cancer and two adenomas did not. On the other hand, neither of the two carcinomas
      in patient 1 showed microsatellite instability. To our knowledge, there has been
      no previous report of microsatellite instability in multiple gastric cancers. In
      this report, we describe a case that revealed such a heterogeneity of the
      microsatellite instability, in which the carcinogenic process of each tumor may
      undergo different genetic alterations even under the same genetic conditions and
      background.

PMID- 7717332
TI  - Hepatic manifestations of porphyria cutanea tarda in a patient with AIDS.

PMID- 7717331
TI  - Meigs' syndrome due to Brenner tumor mimicking lupus peritonitis in a patient
      with systemic lupus erythematosus.

PMID- 7717333
TI  - Fulminant hepatic failure associated with etodolac use.
AB  - Etodolac is a new pyranocarboxylic acid nonsteroidal anti-inflammatory agent with
      a unique chemical structure indicated for use in patients with painful
      musculoskeletal disorders and rheumatoid disease. Hepatotoxicity, in the form of
      reversible elevations in transaminases or bilirubin, occurs rarely. We present
      the first reported case of fulminant hepatic failure related to etodolac.

PMID- 7717334
TI  - Primary adenocarcinoma of the appendix: an unusual presentation.

PMID- 7717335
TI  - Diagnostic value of endoscopic ultrasonography in an unusual case of gastric
      cyst.
AB  - Using endoscopic ultrasonography, we diagnosed a gastric antral submucosal cyst
      with a papillous protrusion in a 71-yr-old woman, apparently the first such case
      to be detected by this method. Endoscopic ultrasonography demonstrated a well
      marginated hypoechoic area with papillary tumor in the submucosal layer that did
      not extend to the muscularis propria. The lesion was diagnosed as a gastric
      submucosal cyst. CT and transabdominal ultrasound each failed to detect the
      intracystic papillary tumor. Follow-up endoscopic ultrasonography performed 6
      months later revealed an increase in the diameter of the cyst and the papillary
      tumor. The patient then underwent a partial gastrectomy for a suspected
      malignancy. The resected specimen showed a cystic lesion with papillary tumor.
      Although no malignancy was present, examination of cross-sections of the resected
      specimen gave results consistent with the endoscopic ultrasonographic findings.
      Endoscopic ultrasonography is thus useful in assessing the nature of a submucosal
      gastric cyst in detail and in monitoring patients with this lesion.

PMID- 7717336
TI  - Esophagus duplication in a young adult.

PMID- 7717337
TI  - Antibiotics in acute pancreatitis: the debate revisited.

PMID- 7717338
TI  - Sleep and esophageal function: brain talk.

PMID- 7717339
TI  - Don't forget cholecystostomy in the era of ERCP and laparoscopic cholecystectomy.

PMID- 7717340
TI  - Response to Drs. Katz and Carey: North American Conference of Gastroenterology
      Fellows.

PMID- 7717341
TI  - Low-cost, office-based, screening colonoscopy.

PMID- 7717342
TI  - Treatment of pyrosis does not insure adequate control of gastric acid reflux.

PMID- 7717343
TI  - New insight in the mechanism of omeprazole antimicrobial combinations to
      eradicate Helicobacter pylori.

PMID- 7717344
TI  - pH and cure of H. pylori infection: it is difficult to have insights when one is
      in the dark.

PMID- 7717345
TI  - Intrahepatic cholestasis due to ticarcillin-clavulanate.

PMID- 7717346
TI  - Antibodies anti-parvovirus B19 in chronic hepatitis C virus infection.

PMID- 7717347
TI  - Endoscopic ligation for ruptured duodenal varices.

PMID- 7717348
TI  - Interferon-alpha is effective in the treatment of chronic hepatitis C.

PMID- 7717349
TI  - Helicobacter pylori and serum pepsinogen A, pepsinogen C, and gastrin: a
      methodological note.

PMID- 7717350
TI  - Diabetes: an ignored complication of sarcoidosis?

PMID- 7717351
TI  - Defective hepatic glutathione S-transferase in Rotor's syndrome.

PMID- 7717352
TI  - Surgically-assisted diagnostic laparoscopy.

PMID- 7717354
TI  - Granular cell tumor of the colon.

PMID- 7717353
TI  - Renal carcinoma metastases presenting as duodenal obstruction.

PMID- 7717355
TI  - Pathogenesis of choledochal cyst.

PMID- 7717356
TI  - The contribution of the social environment to host resistance. The Fourth Wade
      Hampton Frost Lecture. 1976.

PMID- 7717357
TI  - Lipoprotein(a) levels in the Japanese population: influence of age and sex, and
      relation to atherosclerotic risk factors. The Jichi Medical School Cohort Study.
AB  - The authors studied the distribution of lipoprotein(a) (Lp(a)) levels with
      stratification for age and sex, as well as the relation between Lp(a) and
      atherosclerotic risk factors in a large Japanese population between 1992 and
      1993. The subjects were 1,235 males and 1,762 females over 30 years old. Lp(a)
      was measured by an enzyme-linked immunosorbent assay. Lp(a) levels were higher in
      females than in males. The increase in Lp(a) with age was statistically
      significant, and the proportion of subjects with Lp(a) levels > 30 mg/dl also
      increased with age. In the obese subjects (body mass index (BMI) (kg/m2) > 26),
      Lp(a) levels were lower than in the non-obese subjects (BMI < or = 26) (p < 0.01
      in males; p < 0.05 in females). Male alcohol drinkers had lower Lp(a) levels than
      nondrinkers (p < 0.05). Age, low density lipoprotein subtracting Lp(a)
      cholesterol [Lp(a) x 0.3], and fibrinogen level were all positively correlated
      with Lp(a) in both sexes. Alcohol consumption (g/day) and triglycerides were
      inversely correlated with Lp(a) in males, while total cholesterol subtracting
      Lp(a) cholesterol [Lp(a) x 0.3], high density lipoprotein, and factor VII were
      positively correlated in females. Multiple logistic regression analysis showed
      that triglycerides in males and BMI and fibrinogen in females were significant
      independent variables. The authors conclude that Lp(a) level is affected by
      various factors, such as alcohol drinking, BMI, sex, and age, and is not only
      correlated with lipid levels but also with hemostatic factors such as fibrinogen
      and factor VII.

PMID- 7717358
TI  - Role of smoking in the U-shaped relation of cholesterol to mortality in men. The
      Framingham Study.
AB  - Elevated mortality has been reported at extremes of the serum total cholesterol
      distribution, with increased coronary mortality reported at high total
      cholesterol levels and increased cancer and non-cardiovascular/non-cancer
      mortality at low total cholesterol levels. The authors used data collected on
      1,959 males aged 35-69 years from the fourth Framingham Study examination to
      analyze the relations between total serum cholesterol levels and 409 coronary
      deaths, 325 cancer deaths, and 534 other deaths for a 32-year follow-up. Age- and
      risk factor-adjusted Cox regressions were computed. Nonlinear (U-shaped)
      relations were investigated with the use of quadratic regression and with dummy
      variables using the 160-199 mg/dl group as the comparison group. Subset analyses
      investigated the relation in smokers and men who drank > or = 14 alcoholic drinks
      per week. All analyses were repeated removing those with existing cardiovascular
      disease and cancer and those who died during the first 5 years of follow-up. A
      significant U-shaped relation with all-cause mortality was noted, as were an
      inverse relation to cancer mortality and a monotonic increasing relation with
      coronary disease mortality. In subset analyses, the association of low serum
      cholesterol (< 160 mg/dl) with cancer mortality was observed in men who smoked
      cigarettes. Compared with the 160-199 mg/dl group, the relative risk was 3.72 (p
      = 0.0001, 95% confidence interval 1.91-7.25). Studies of the relation of low
      total serum cholesterol levels, cigarette smoking, and cancer are needed.

PMID- 7717359
TI  - Estrogen replacement therapy and fatal ovarian cancer.
AB  - The authors examined the relation between use of estrogen replacement therapy and
      ovarian cancer mortality in a large prospective mortality study of 240,073 peri-
      and postmenopausal women, none of whom had a prior history of cancer,
      hysterectomy, or ovarian surgery at enrollment in 1982. During 7 years of follow
      up, 436 deaths from ovarian cancer occurred. Cox proportional hazard regression
      was used to adjust for other risk factors. Ever use of estrogen replacement
      therapy was associated with a rate ratio for fatal ovarian cancer of 1.15 (95%
      confidence interval (CI) 0.94-1.42). The mortality rate ratio increased with
      duration of use prior to entry to this study to 1.40 (95 CI% 0.92-2.11) with 6-10
      years of use and 1.71 (95% CI 1.06-2.77) with > or = 11 years of use. The
      increase in mortality associated with > or = 6 years of use was observed in both
      current users (rate ratio (RR) = 1.72, 95% CI 1.01-2.90) and former users at
      study entry (RR = 1.48, 95% CI 0.99-2.22), relative to never users. Risk
      associated with use was not modified by any of the other risk factors. These data
      suggest that long-term use of estrogen replacement therapy may increase the risk
      of fatal ovarian cancer.

PMID- 7717360
TI  - Incidence of perforated ulcer in western Norway, 1935-1990: cohort- or period
      dependent time trends?
AB  - Previous reports have shown that peptic ulcer mortality follows birth cohorts. To
      the authors' knowledge, temporal variation in ulcer incidence has not been
      studied. Therefore, they present incidence data for a defined area of western
      Norway where 1,312 patients born between 1845 and 1975 were treated for ulcer
      perforation between 1935 and 1990. A rise and subsequent fall in incidence was
      observed in successive birth cohorts for both sexes, with the highest incidence
      observed for males born between 1900 and 1919 and females born between 1920 and
      1929. Age-period-cohort analyses based on Poisson regression techniques were
      adapted to provide a statistical tool for testing specific cohort and period
      effects. Age-cohort models without period effects explained the variations in
      incidence for both sexes and all ulcer locations, suggesting cohort-dependent
      etiology. A cohort pattern in prevalence of smoking partly explained the cohort
      pattern in perforation risks for both sexes. No period effects were seen that
      could be attributed to the increase in the sale of non-steroidal anti
      inflammatory drugs, to the introduction of antibiotics around 1950, or to World
      War II. Susceptibility to ulcer perforation seems to follow birth cohorts, and
      major etiologic factors should be sought in prenatal life, in childhood, or in
      life-style patterns that follow birth cohorts.

PMID- 7717361
TI  - Adult height and risk of breast cancer among US black women.
AB  - Adult height has been positively associated with the risk of breast cancer in a
      number of recent investigations. The authors assessed height in relation to
      breast cancer risk in a case-control study of US black women aged 25-69 years;
      674 hospital patients with newly diagnosed breast cancer and 1,155 controls
      hospitalized for nonmalignant conditions unrelated to height were interviewed.
      After control for multiple confounders, the relative risk estimate for women < 61
      inches (< 154.9 cm) tall was 0.5 (95% confidence interval (Cl) 0.3-0.7) relative
      to the median height of 64-65 inches (162.6-165.1 cm). Among women > or = 61
      inches (> or = 154.9 cm) tall, there was little indication of any variation in
      risk with increasing height. The findings suggest that short stature is
      associated with a decreased risk of breast cancer in US black women.

PMID- 7717363
TI  - How accurate is self-reported family history of colorectal cancer?
AB  - Much of the evidence that supports a relation between a positive family history
      of and increased risk for colorectal cancer is based on information obtained
      exclusively from patients. There have been few assessments of the accuracy of
      such data. The validity of self-reported family history of colorectal cancer was
      assessed in the course of a case-control study of colorectal adenomas conducted
      among patients aged 20-75 years who underwent colonoscopy in Brisbane, Australia
      between 1980 and 1985. Family histories reported by a subsample of 237
      colonoscopy patients (74 cases and 163 controls) were compared with relatives'
      medical records and death certificates. Patients' reports of colorectal cancer in
      90 relatives were confirmed for 70 (77.8%; 95% confidence interval (CI) 67.8
      85.9). Among 124 reports by patients of relatives who had other abdominal cancer
      or bowel conditions, 114 (91.9%; 95% CI 85.7-96.1) were confirmed to be correct,
      while 10 (8.1%) were found to be colorectal cancer. Finally, 105 (99.1%; 95% CI
      94.9-100.0) of a random sample of 106 completely negative reports by patients
      were confirmed to be correct. Overall, 77% of positive family histories (any
      positive relatives) were confirmed, and it was estimated that 98% of negative
      family histories (no positive relatives) were correct. Cases were slightly more
      accurate than controls in reporting both positive and negative histories among
      their relatives. By extrapolation of these results to the total sample of 1,244
      patients in the larger case-control study, sensitivity of self-reported positive
      family history was estimated to be 0.87 among cases and 0.82 among controls, and
      specificity was estimated to be 0.97 in both groups.

PMID- 7717362
TI  - Public drinking water contamination and birth outcomes.
AB  - The effects of public drinking water contamination on birth outcomes were
      evaluated in an area of northern New Jersey. After excluding plural births and
      chromosomal defects, 80,938 live births and 594 fetal deaths that occurred during
      the period 1985-1988 were studied. Information on birth outcome status and
      maternal risk factors was obtained from vital records and the New Jersey Birth
      Defects Registry. Monthly exposures during pregnancy were estimated for all
      births using tap water sample data. Odds ratios of > or = 1.50 were found for the
      following: total trihalomethanes with small for gestational age, central nervous
      system defects, oral cleft defects, and major cardiac defects; carbon
      tetrachloride with term low birth weight, small for gestational age, very low
      birth weight, total surveillance birth defects, central nervous system defects,
      neural tube defects, and oral cleft defects; trichloroethylene with central
      nervous system defects, neural tube defects, and oral cleft defects;
      tetrachloroethylene with oral cleft defects; total dichloroethylenes with central
      nervous system defects and oral cleft defects; benzene with neural tube defects
      and major cardiac defects; and 1,2-dichloroethane with major cardiac defects.
      Total trihalomethane levels > 100 ppb reduced birth weight among term births by
      70.4 g. By itself, this study cannot resolve whether the drinking water
      contaminants caused the adverse birth outcomes; therefore, these findings should
      be followed up utilizing available drinking water contamination databases.

PMID- 7717364
TI  - Validity of mother's report of father's occupation in a study of paternal
      occupation and congenital malformations.
AB  - Agreement between the mother's and father's report of the father's occupation was
      assessed in a case-control study of paternal occupation and birth defects. Cases
      were identified from births registered with the Metropolitan Atlanta Congenital
      Defects Program between 1968 and 1980; controls were selected from liveborn
      infants without defects. Both parents were sought for interview, and each parent
      was asked about the father's job history for 2 years prior to the infant's death.
      This concordance analysis is based on 3,739 case infants and 2,279 control
      infants for whom both parents were interviewed. The authors considered the
      father's report of his occupation as correct, and they assessed the ability of
      the mother to report the same occupation(s) during a 7-month period around
      conception. The exact agreement between mother's and father's report of the
      father's occupation was 59%. Agreement improved slightly with increasing family
      income and when fathers were college graduates. Female partners were not accurate
      proxy respondents in this study of paternal occupation and birth defects, which
      suggests that investigators should interview both parents in studies of paternal
      exposures and reproductive outcomes, i.e., mothers for pregnancy history and
      maternal confounders and fathers for occupational history and paternal
      confounders.

PMID- 7717365
TI  - Injury mortality among Iowa farmers, 1980-1988: comparison of PMR and SMR
      approaches.
AB  - State and provincial proportional mortality studies in the United States and
      Canada have found increased ratios of overall injury mortality among farmers,
      including occupational injuries and other unintentional injuries, such as those
      from motor vehicle crashes and fires, as well as suicides. In contrast,
      Scandinavian standardized mortality (morbidity) studies have found no increase in
      the injury fatality or morbidity ratios of farmers in comparison with the rest of
      the population. This study reviews the injury mortality of Iowa farmers for the
      years 1980-1988. Among white male farmers, we found an increased proportional
      mortality ratio for all injuries of 1.26 (95% confidence interval (CI) 1.21
      1.31). In part, this was a result of the increased proportional mortality ratio
      for at-work injuries of 3.77 (95% CI 3.35-4.24), but there were also elevated
      proportional mortality ratios for such nonoccupational injuries as suicides, 1.20
      (95% CI 1.09-1.32), motor vehicle crashes, 1.23 (95% CI 1.12-1.34), and
      electrocutions, 1.78 (95% CI 1.08-2.95). For younger farmers aged 20-64 years, we
      calculated standardized mortality ratios as well. The standardized mortality
      ratios were generally within 10% of the proportional mortality ratios, which
      suggests that the differences between North America and Scandinavia are not the
      result of methodological differences, but are more likely related to differences
      in environmental exposures and safety practices.

PMID- 7717366
TI  - Re: "Determinants of papillary cancer of the thyroid".

PMID- 7717367
TI  - Idiopathic osteonecrosis, hypofibrinolysis, high plasminogen activator inhibitor,
      high lipoprotein(a), and therapy with Stanozolol.
AB  - In five patients with idiopathic osteonecrosis (ON) of the hip, four having
      hypofibrinolysis mediated by high plasminogen activator inhibitor (PAI-Fx), and
      one with high Lp(a), our specific aim was to determine whether therapy (Rx) with
      the anabolic-androgenic steroid, Stanozolol (6 mg/day), would normalize PAI-Fx
      and Lp(a) and thus potentially ameliorate ON. Prior to Rx, none of the four
      patients with high PAI-Fx could normally elevate tissue plasminogen activator
      (tPA-Fx) after 10 min venous occlusion at 100 mm Hg. After 12-18 weeks on Rx, PAI
      Fx and stimulated tPA-Fx normalized in all four patients. Prior to Rx, mean (SD)
      stimulated tPA-Fx was low, 0.4 +/- 0.3 IU/ml (lower limit of normal 2.28 IU/ml).
      On Rx, stimulated tPA-Fx normalized, rising to 2.83 +/- 1.9 IU/ml, P = .004.
      Prior to Rx, mean (SD) basal PAI-Fx was high, 99 +/- 68 (upper limit of normal
      26.9 U/ml), and fell on Rx to 22.5 +/- 22, P = .004. In two of the five patients
      normalization of hypofibrinolysis or high Lp(a) was accompanied by major
      symptomatic improvement. Prior to Rx, and 2 years after onset of unilateral hip
      pain, one of the four patients with high PAI-Fx and low stimulated tPA-Fx could
      walk only one block painfully. After 8 weeks on Stanozolol Rx, and continuing
      through 54 weeks on Rx, he walked 2 miles per day without pain, despite
      radiographic progression of ON. In three of the four patients with high PAI and
      with osteonecrosis present 0.3, 2, and 6 years prior to Stanozolol Rx, there was
      no clinical improvement after 14-156 weeks of Rx despite normalization of
      stimulated tPA-Fx and PAI-Fx. The fifth patient, 1 month after onset of disabling
      hip pain, had normal PAI-Fx but high Lp(a) (27 mg/dl), and MRI evidence of bone
      marrow edema ("transient osteoporosis").(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717368
TI  - Design and validation of a bedside decision instrument to elicit a patient's
      preference concerning allogenic bone marrow transplantation in chronic myeloid
      leukemia.
AB  - The objective of this study was to design and validate a bedside decision
      instrument to be used by patients with chronic myeloid leukemia and their
      physicians in deciding between the therapeutic alternatives of bone marrow
      transplantation and conservative management during the early phase of disease. A
      decision board was constructed containing detailed scenarios associated with the
      treatment alternatives, together with estimates of survival probabilities at
      various periods of followup. The instrument was tested on 42 healthy hospital
      personnel and validated by measuring the extent to which systematic alterations
      in the scenarios with respect to toxicities and survival probabilities produced
      predicted shifts in treatment preferences. A subgroup of respondents was
      randomized to receive information through the decision board alone or a shorter
      and less informative version of the instrument, followed by the decision board.
      The direction and strength of stated preferences were compared, together with
      satisfaction for these preferences. The direction and strength of preferences
      between bone marrow transplantation or conservative chemotherapy were influenced
      in a predictable way by changes in the toxicity and survival descriptions in the
      scenarios. Using the test-retest method in 16 subjects, the stated preferences
      were found to be highly reliable (intraclass correlation coefficient, 0.87). The
      mean level of satisfaction with the stated preference, on a scale from not at all
      satisfied = 1 to very satisfied = 5, was higher for those exposed to the decision
      board (3.7, SD 1.06) compared with those presented with the short version (2.95,
      SD 0.67) (P < 0.01). The results demonstrate the feasibility and acceptability of
      the instrument in healthy individuals. The preferences elicited by the instrument
      appear to be reliable and valid according to prespecified constructs of the
      relation between the information provided and the preferences predicted. These
      results support further testing of this approach in actual patients.

PMID- 7717369
TI  - Treatment of acute myelogenous leukemia in patients over 50 years of age with V
      TAD: a Southwest Oncology Group study.
AB  - Acute myelogenous leukemia (AML) in the elderly continues to have a poor
      prognosis and new treatment approaches are needed. This Phase II trial was
      undertaken to evaluate the complete remission rate and toxicity of a
      chemotherapeutic regimen including etoposide and 6-thioguanine, combined with
      reduced doses of cytosine arabinoside and daunorubicin (V-TAD) in individuals
      greater than 50 years of age with AML. Thirty-five patients, ranging in age from
      51 to 80 years (median, 66 years), were registered onto the study. Twenty-nine
      patients were entered at the first dose level (daunomycin 20 mg/m2 days 1 and 2,
      ara-C 75 mg/m2 days 1-5, 6-thioguanine 75 mg/m2 every 12 hr days 1-5, and
      etoposide 50 mg/m2 days 1, 2, and 3) and six patients underwent therapy at the
      second dose level (ara-C 75 mg/m2 days 1-7 with the remainder of the regimen
      unchanged). After achieving a complete remission, patients underwent two to three
      consolidation cycles of chemotherapy. Thirty-one patients were evaluable for
      response. Thirteen patients (ten of twenty-five at the first dose level and three
      of six at the second dose level) achieved a complete remission (42%). Median
      remission duration was 6 months (range 1-21 months). The current regimen, while
      tolerated, did not result in improved survival compared with prior treatment
      regimens because of a high incidence of resistant and recurrent leukemia.

PMID- 7717370
TI  - Myelodysplastic syndrome treatment with danazol and cis-retinoic acid.
AB  - We prospectively treated 46 patients with favorable myelodysplastic syndrome
      classified as refractory anemia (RA), refractory cytopenia (RC), or refractory
      anemia with ringed sideroblasts (RARS). These patients received one of two
      schedules of 13-Cis-Retinoic Acid (low dose 80 mg daily for 6 months vs. high
      dose 200 mg po daily for 3 months), or Danazol (800 mg po daily for 3 months),
      and were crossed over to the alternative drug in the absence of response or at
      progression. Using strict criteria of response we found little objective evidence
      of activity for either compound. Only two minor responses were seen among 22
      patients treated with low dose 13-CRA, 1 response among 20 cases that received
      high dose 13-CRA, and 1 partial response and 1 minor response to Danazol among 34
      cases. Neither 13-Cis-Retinoic Acid nor Danazol appear active enough in patients
      with favorable myelodysplastic syndrome to justify their use.

PMID- 7717371
TI  - INR reporting in Canadian medical laboratories. Thrombosis Interest Group of
      Canada.
AB  - A written survey of all licensed medical laboratories in Canada performing
      coagulation testing was performed to investigate the level of knowledge and
      overall usage of the INR system for reporting prothrombin time results in medical
      laboratories. There was an overall response rate of 857 of 1,228 laboratories
      surveyed. Fifty-seven percent of responding laboratories utilized some format of
      INR reporting. The ISI of the individual thromboplastin utilized was known by 89%
      of laboratories. The ISI of the thromboplastin utilized was known to be specific
      for the particular reagent/instrument combination in 44% of cases. Fifty-five
      percent of client physicians preferred PT results to be reported in seconds while
      42% desired an INR format. The situation in Canada is similar to the United
      States in that further education regarding the INR system for PT reporting is
      required by both medical laboratories and physicians.

PMID- 7717372
TI  - Lupus anticoagulant in children with thrombosis.
AB  - Nineteen children who presented with thromboses over a 7-year period were found
      to have a lupus anticoagulant (LA). The initial thrombosis was proximal deep vein
      thrombosis (DVT) in six children, central nervous system (CNS) in five, primary
      pulmonary in four, distal DVT in two, central venous in one, and proximal
      arterial in one. Five children were diagnosed with systemic lupus erythematosus
      (SLE), including two children for whom thrombosis was the presenting sign of SLE.
      The remaining 14 children were diagnosed with the antiphospholipid antibody (APA)
      syndrome. The APA syndrome was manifest by venous or arterial thrombosis in
      association with a positive LA; positive anticardiolipin antibodies and a fine,
      speckled antinuclear antibody (ANA) pattern were additionally found in the
      majority of children. Approximately one-half of the children with SLE or the APA
      syndrome had a pulmonary embolus, and one-half developed recurrent thrombosis.
      Oral anticoagulation with coumadin to achieve an INR of > 2.0 prevented
      thrombosis recurrence. The recognition of a LA in children with thrombosis
      necessitates evaluation for SLE, APA, and other autoantibodies.

PMID- 7717373
TI  - Reliability of automated platelet counts: comparison with manual method and
      utility for prediction of clinical bleeding.
AB  - The 20 x 10(9)/L (20,000/microliters) threshold for prophylactic platelet
      transfusion may be unnecessarily high. The widespread use of this threshold may
      reflect lack of confidence in the reliability of low platelet counts. We
      evaluated the performance of automated platelet counts and their relation to
      clinical bleeding. First, we prepared serial blood dilutions with "target"
      platelet counts from 2 to 40 x 10(9)/L. For the 48 measurements on 2 x 10(9)/L
      "target" dilutions, values of 1 or 2 x 10(9)/L were obtained with the Sysmex NE
      8000 analyzer (mean 1.44 x 10(9)/L; SD 0.31 x 10(9)/L). Similarly, for 5 x
      10(9)/L "target" counts, automated counts were 3-6 x 10(9)/L (mean 4.42 x
      10(9)/L; SD 0.18 x 10(9)/L). Similar results were observed with all other
      "target" levels, with coefficients of variation (CV) from 6.39% to 7.71% with 10
      40 x 10(9)/L "target" values. Secondly, we compared triplicate automated and
      manual platelet counts on thrombocytopenic patients with platelet counts from 4
      30 x 10(9)/L. The triplicate automated platelet counts differed by no more than 5
      x 10(9)/L among themselves, whereas the manual counts varied by as much as 30 x
      10(9)/L. Mean platelet counts: automated, 14.40 x 10(9)/L (CV 10.12%); manual,
      16.48 x 10(9)/L (CV 30.39%) (P = 0.038 for counts; P < 0.001 for CV). Finally, we
      prospectively evaluated bleeding in thrombocytopenic patients (1,809 patient-days
      of observation). Univariate and multivariate logistic regression analysis
      revealed highly significant correlations between the automated platelet count and
      major and minor bleeding manifestations. Thus, automated platelet counts are
      highly reliable and accurately predict clinical bleeding. The use of automated
      analyzers should facilitate improved prophylactic platelet transfusion protocols.

PMID- 7717374
TI  - Biochemical indices of vitamin B12 nutrition in pregnant patients with subnormal
      serum vitamin B12 levels.
AB  - To determine the significance of the commonly observed fall in serum vitamin B12
      levels during pregnancy, serum levels of the B12 metabolites methylmalonic acid
      (MMA) and homocysteine (Hcy) were measured in a group of 50 pregnant patients
      with subnormal serum B12 (range 45-199 pg/ml) and the results compared with those
      of 25 pregnant controls (serum B12(208-580) pg/ml). Mean values for serum MMA and
      total Hcy in the subnormal B12 group were 445.4 nmol/L and 7.03 mumol/L,
      respectively, which were not significantly different from the mean MMA of 440.5
      nmol/L and Hcy of 6.88 nmol/L in the controls. For the total group of patients,
      neither serum MMA nor serum Hcy levels correlated with serum B12. One-third of
      pregnant patients showed elevated serum MMA values, independent of B12 status.
      Significant elevation of serum Hcy was detected in only two patients, both with
      subnormal serum B12 and hematological evidence of B12 deficiency. We conclude
      that the usual fall in serum B12 concentration in pregnancy does not reflect B12
      deficiency at the biochemical level. In establishing true B12 deficiency in
      pregnancy, the serum Hcy level (in the absence of folate deficiency) but not
      serum MMA, is of value.

PMID- 7717376
TI  - Durable complete remission of macroglobulinemia after splenectomy: a report of
      two cases and review of the literature.
AB  - Two patients with macroglobulinemia (monoclonal IgM in the serum) and massive
      splenomegaly were incapacitated by progressive disease refractory to standard
      chemotherapy. In each case, palliative splenectomy was followed by a prompt,
      complete, and unexpected clinical remission with disappearance from the serum of
      the monoclonal IgM component. One patient remains free of disease 12 years after
      splenectomy. The other patient remained free of detectable macroglobulinemia for
      13 years after splenectomy. A review of the literature revealed other cases of
      remission of macroglobulinemia attributable to splenectomy alone. Data in humans
      and animals suggest that the spleen may facilitate IgM secretion by normal and
      malignant B lymphocytes. Splenectomy should be considered a possible treatment
      option for patients with massive splenomegaly and macroglobulinemia who progress
      on chemotherapy.

PMID- 7717375
TI  - Bone marrow transplantation in a young child with sickle cell anemia.
AB  - Bone marrow transplantation (BMT) is the only curative therapy available for
      hemoglobinopathies. BMT was performed on a young child with sickle cell anemia
      (SCA) after approximately 9 months of transfusion therapy following her initial
      stroke. The patient received a matched sibling donor (sickle trait) BMT. The
      conditioning regimen consisted of busulfan 4 mg/kg/day x 4, cyclophosphamide 50
      mg/kg/day x 4. Graft vs. host disease prophylaxis was daily cyclosporine for 6
      months. There were no significant complications during BMT. Engraftment occurred
      on day +17 and the patient was transfusion independent since day +45. Pre-BMT
      cerebral arteriography showed multiple stenotic cerebral vessels and a moya-moya
      pattern. Perfusion MRI demonstrated reduced capillary perfusion. Approximately
      170 days after BMT the patient experienced episodes of transient left-sided
      weakness and speech problems. Neuroimaging revealed progression of large vessel
      pathology by angiography despite significant improvement in cortical perfusion
      (MR perfusion scan). Molecular analysis by PCR and DNA fingerprinting confirmed
      absence of mixed mosaicism. Rheologic evaluation showed normal corrected bulk
      viscosity. It is possible that progression of large vessel pathology and return
      of clinical symptoms in the face of normal rheologic parameters may be due to
      worsening of the already damaged cerebral vessels by the BMT conditioning
      regimen. Further evaluations of patients with SCA undergoing BMT after a stroke
      are needed to answer this question.

PMID- 7717377
TI  - Fletcher factor deficiency in a 9-year-old girl: mechanisms of the contact
      pathway of blood coagulation.

PMID- 7717378
TI  - Multi-drug resistance to Streptococcus pneumoniae in sickle cell anemia.

PMID- 7717379
TI  - Discrimination of Hb D Los Angeles (B121 Glu-Gln) and Hb Beograd (B121 Glu-Val)
      by dual restriction enzyme analysis.
AB  - Hb D Los Angeles (B121 Glu-Gln) and Hb Beograd (B121 Glu-Val) can be identified
      by different techniques. Here we describe a dual restriction enzyme digestion
      protocol (EcoR IG AATTC) and Tsp509 I ( AATT) for the discrimination of these
      variants.

PMID- 7717380
TI  - High-dose methylprednisolone is an alternative treatment for adults with
      autoimmune thrombocytopenic purpura refractory to intravenous immunoglobulins and
      oral corticosteroids.
AB  - Eight patients with severe chronic autoimmune thrombocytopenic purpura (AITP)
      refractory to high-dose intravenous immunoglobulin (IVIgG) and/or oral prednisone
      were treated with one to three infusions of high-dose methylprednisolone (HDMP)
      (15 mg/kg/day). The mean platelet count before treatment was 12 +/- 10 x 10(9)/L.
      HDMP therapy led to a safe platelet count (> 50 x 10(9)/L) after 2-5 days in five
      patients, and a minimal platelet increase (34 x 10(9)/L) able to stop bleeding in
      a sixth patient. The effect of HDMP was, however, transient in four of five
      responders. No side effects were observed, even in the four patients older than
      70 years. HDMP thus appears to be a good alternative in emergency situations or
      prior to surgery for patients with AITP refractory to conventional therapy.

PMID- 7717381
TI  - Oxidized LDL induces serotonin release from blood platelets.
AB  - Oxidized low-density lipoprotein (LDL) induces a release of serotonin from
      morphologically resting platelets and shape changed platelets. This suggests that
      oxidized LDL, a newly reported weak agonist, contributes to atherogenesis and
      thrombogenesis by stimulating platelets.

PMID- 7717383
TI  - Down's syndrome associated with the hypereosinophilic syndrome.

PMID- 7717382
TI  - Hb Questembert is due to a base substitution (T-->C) in codon 131 of the alpha 2
      globin gene and has an alpha-thalassemia biosynthetic ratio.

PMID- 7717384
TI  - Hairy cell leukemia: treatment results and association with secondary malignancy.

PMID- 7717385
TI  - Successful systemic thrombolysis of hepatic vein thrombosis in a patient with
      promyelocytic leukemia treated with all-trans retinoic acid.

PMID- 7717386
TI  - Acute onset of severe autoimmune hemolytic anemia after treatment with 2
      chlorodeoxyadenosine for chronic lymphocytic leukemia.

PMID- 7717387
TI  - Abnormal hemoglobins in Mauritius Island.

PMID- 7717388
TI  - False-negative D-dimer test in a patient with disseminated intravascular
      coagulation.

PMID- 7717389
TI  - Diverse mutations in the aldolase B gene that underlie the prevalence of
      hereditary fructose intolerance.

PMID- 7717390
TI  - Allelic association between the HUMF13A01 (AAAG)n STR locus and a nearby two-base
      insertion/deletion polymorphic marker.

PMID- 7717391
TI  - Gene-environment interaction and public health.

PMID- 7717392
TI  - Cervicomedullary junction compression in infants with achondroplasia: when to
      perform neurosurgical decompression.

PMID- 7717394
TI  - Epidemiological evaluation of the use of genetics to improve the predictive value
      of disease risk factors.
AB  - The prevention of common diseases relies on identifying risk factors and
      implementing intervention in high-risk groups. Nevertheless, most known risk
      factors have low positive predictive value (PPV) and low population-attributable
      fraction (PAF) for diseases (e.g., cholesterol and coronary heart disease). With
      advancing genetic technology, it will be possible to refine the risk-factor
      approach to target intervention to individuals with risk factors who also carry
      disease-susceptibility allele(s). We provide an epidemiological approach to
      assess the impact of genetic testing on the PPV and PAF associated with risk
      factors. Under plausible models of interaction between a risk factor and a
      genotype, we derive values of PPV and PAF associated with the joint effects of a
      risk factor and a genotype. The use of genetic testing can markedly increase the
      PPV of a risk factor. PPV increases with increasing genotype-risk factor
      interaction and increasing marginal relative risk associated with the factor, but
      it is inversely proportional to the prevalences of the genotype and the factor.
      For example, for a disease with lifetime risk of 1%, if all the risk-factor
      effect is confined to individuals with a susceptible genotype, a risk factor with
      10% prevalence and disease relative risk of 2 in the population will have a
      disease PPV of 1.8%, but it will have a PPV of 91.8% among persons with a
      genotype of 1% prevalence. On the other hand, genetic testing and restriction of
      preventive measures to those susceptible may decrease the PAF of the risk factor,
      especially at low prevalences of the risk factor and genotype.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7717393
TI  - Genes of the copper pathway.

PMID- 7717396
TI  - Mutations in the gene for X-linked adrenoleukodystrophy in patients with
      different clinical phenotypes.
AB  - Recently, the gene for the most common peroxisomal disorder, X-linked
      adrenoleukodystrophy (X-ALD), has been described encoding a peroxisomal membrane
      transporter protein. We analyzed the entire protein-coding sequence of this gene
      by reverse-transcription PCR, SSCP, and DNA sequencing in five patients with
      different clinical expression of X-ALD and in their female relatives; these
      clinical expressions were cerebral childhood ALD, adrenomyeloneuropathy (AMN),
      and "Addison disease only" (ADO) phenotype. In the three patients exhibiting the
      classical picture of severe childhood ALD we identified in the 5' portion of the
      X-ALD gene a 38-bp deletion that causes a frameshift mutation, a 3-bp deletion
      leading to a deletion of an amino acid in the ATP-binding domain of the ALD
      protein, and a missense mutation. In the patient with the clinical phenotype of
      AMN, a nonsense mutation in codon 212, along with a second site mutation at codon
      178, was observed. Analysis of the patient with the ADO phenotype revealed a
      further missense mutation at a highly conserved position in the ALDP/PMP70
      comparison. The disruptive nature of two mutations (i.e., the frameshift and the
      nonsense mutation) in patients with biochemically proved childhood ALD and AMN
      further strongly supports the hypothesis that alterations in this gene play a
      crucial role in the pathogenesis of X-ALD. Since the current biochemical
      techniques for X-ALD carrier detection in affected families lack sufficient
      reliability, our procedure described for systematic mutation scanning is also
      capable of improving genetic counseling and prenatal diagnosis.

PMID- 7717395
TI  - Identification of polymorphisms and sequence variants in the human homologue of
      the mouse natural resistance-associated macrophage protein gene.
AB  - The most common mycobacterial disease in humans is tuberculosis, and there is
      evidence for genetic factors in susceptibility to tuberculosis. In the mouse, the
      Bcg gene controls macrophage priming for activation and is a major gene for
      susceptibility to infection with mycobacteria. A candidate gene for Bcg was
      identified by positional cloning and was designated "natural resistance
      associated macrophage protein gene" (Nramp1), and the human homologue (NRAMP1)
      has recently been cloned. Here we report on (1) the physical mapping of NRAMP1
      close to VIL in chromosome region 2q35 by PCR analysis of somatic cell hybrids
      and YAC cloning and (2) the identification of nine sequence variants in NRAMP1.
      Of the four variants in the coding region, there were two missense mutations and
      two silent substitutions. The missense mutations were a conservative alanine-to
      valine substitution at codon 318 in exon 9 and an aspartic acid-to-asparagine
      substitution at codon 543 in the predicted cytoplasmic tail of the NRAMP1
      protein. A microsatellite was located in the immediate 5' region of the gene,
      three variants were in introns, and one variant was located in the 3' UTR. The
      allele frequencies of each of the nine variants were determined in DNA samples of
      60 Caucasians and 20 Asians. In addition, we have physically linked two highly
      polymorphic microsatellite markers, D2S104 and D2S173, to NRAMP1 on a 1.5-Mb YAC
      contig. These molecular markers will be useful to assess the role of NRAMP1 is
      susceptibility to tuberculosis and other macrophage-mediated diseases.

PMID- 7717397
TI  - Two novel SRY missense mutations reducing DNA binding identified in XY females
      and their mosaic fathers.
AB  - Two novel mutations in the sex-determining gene SRY were identified by screening
      DNA from 30 sex-reversed XY females by using the SSCP assay. Both point mutations
      lead to an amino acid substitution in the DNA-binding high-mobility-group domain
      of the SRY protein. The first mutation, changing a serine at position 91 to
      glycine, was found in a sporadic case. The second mutation, leading to
      replacement of a highly conserved proline at position 125 with leucine, is shared
      by three members of the same family, two sisters and a half sister having the
      same father. The mutant SRY proteins showed reduced DNA-binding ability in a gel
      shift assay. Analysis of lymphocyte DNA from the respective fathers revealed that
      they carry both the wild-type and the mutant version of the SRY gene. The fact
      that both fathers transmitted the mutant SRY copy to their offspring implies that
      they are mosaic for the SRY gene in testis as well as in blood, as a result of a
      mutation during early embryonic development.

PMID- 7717398
TI  - Mutational analyses of Tay-Sachs disease: studies on Tay-Sachs carriers of French
      Canadian background living in New England.
AB  - Tay-Sachs disease (TSD) results from mutations in HEXA that cause Hex A
      deficiency. Heterozygote-screening programs have been applied in groups with an
      increased TSD incidence, such as Ashkenazi Jews and French Canadians in Quebec.
      These programs are complicated by benign mutations that cause apparent Hex A
      deficiency but not TSD. Benign mutations account for only approximately 2% of
      Jewish and approximately 36% of non-Jewish enzyme-defined carriers. A carrier
      frequency of 1/53 (n = 1,434) was found in an ongoing prospective analysis of
      persons of French Canadian background living in New England by using an enzyme
      based assay. DNA from enzyme-defined carriers from this population was analyzed
      to determine the molecular basis of Hex A deficiency. Samples (36) were tested
      for common mutations, and samples that were negative for these were screened for
      uncommon or novel mutations by using SSCP analysis. Exons showing mobility shifts
      were sequenced, and most mutations were confirmed by restriction enzyme
      digestion. Known disease-causing mutations were found in nine samples (four had a
      7.6-kb deletion found in 80% of French Canadian TSD alleles), and known benign
      mutations were found in four samples. Seven novel changes were identified,
      including G748A in four samples. The molecular basis of Hex A deficiency in this
      carrier population differs from that of French Canadian TSD patients. Screening
      centers should be aware of the presence of benign mutations among U.S. French
      Canadians or Franco-Americans.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717399
TI  - Insertion of an Alu sequence in the Ca(2+)-sensing receptor gene in familial
      hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.
AB  - Missense mutations in the calcium-sensing receptor (CaR) gene have previously
      been identified in patients with familial hypocalciuric hypercalcemia (FHH) and
      neonatal severe hyperparathyroidism (NSHPT). We studied family members of a Nova
      Scotian deme expressing both FHH and NSHPT and found, by PCR amplification of CaR
      gene exons, that FHH individuals were heterozygous and NSHPT individuals were
      homozygous for an abnormally large exon 7. This is due to an insertion at codon
      877 of an Alu-repetitive element of the predicted-variant/human-specific-1
      subfamily. It is in the opposite orientation to the CaR gene and contains an
      exceptionally long poly(A) tract. Stop signals are introduced in all reading
      frames within the Alu sequence, leading to a predicted shortened mutant CaR
      protein. The loss of the majority of the CaR carboxyl-terminal intracellular
      domain would dramatically impair its signal transduction capability.
      Identification of the specific mutation responsible for the FHH/NSHPT phenotype
      in this community will allow rapid testing of at-risk individuals.

PMID- 7717400
TI  - Leaky splicing mutation in the acid maltase gene is associated with delayed onset
      of glycogenosis type II.
AB  - An autosomal recessive deficiency of acid alpha-glucosidase (GAA), type II
      glycogenosis, is genetically and clinically heterogeneous. The discovery of an
      enzyme-inactivating genomic deletion of exon 18 in three unrelated genetic
      compound patients--two infants and an adult--provided a rare opportunity to
      analyze the effect of the second mutation in patients who displayed dramatically
      different phenotypes. A deletion of Lys-903 in one patient and a substitution of
      Arg for Leu-299 in another resulted in the fatal infantile form. In the adult, a
      T-to-G base change at position -13 of intron 1 resulted in alternatively spliced
      transcripts with deletion of exon 2, the location of the start codon. The low
      level of active enzyme (12% of normal) generated from the leakage of normally
      spliced mRNA sustained the patient to adult life.

PMID- 7717401
TI  - Characterization of nine novel mutations in the CD40 ligand gene in patients with
      X-linked hyper IgM syndrome of various ancestry.
AB  - X-linked immunodeficiency with hyper-IgM (HIGMX-1) is a rare disorder caused by
      defective expression of the CD40 ligand (CD40L) by activated T lymphocytes,
      resulting in inefficient T-B cell cooperation and failure of B cells to undergo
      immunoglobulin isotype switch. In the present work, we describe nine patients of
      various ancestry who bear different mutations in the X chromosome-specific CD40L
      gene. Two of the mutations were nonsense mutations, one each resulting in
      premature stop codons at amino acid residues 39 and 140. Three patients had
      single point missense mutations, one each at codons 126, 140, and 144. Another
      patient had a 4-bp genomic deletion in exon 2, resulting in a frameshift and
      premature termination. Three patients showed insertions, one each of 1, 2, and 4
      nt, probably because of polymerase slippage, resulting in frameshift mutation and
      premature termination. Overall, these observations confirm the heterogeneity of
      mutations in HIGMX-1. However, the identification of two patients whose mutation
      involves codon 140 (previously shown to be altered in two other unrelated
      subjects) suggests that this may be a hotspot of mutation in HIGMX-1. In two
      additional patients with clinical and immunological features indistinguishable
      from canonical HIGMX-1, no mutation was detected in the coding sequence, in the
      5' flanking region, or in the 3' UTR.

PMID- 7717402
TI  - Cytogenetic and molecular studies of Down syndrome individuals with leukemia.
AB  - There is an increased risk of leukemia in Down syndrome (DS) patients, with
      estimates ranging from 14 to 30 times the incidence rate observed for
      chromosomally normal children. Furthermore, one type of leukemia, called
      "transient leukemia" (TL), occurs almost exclusively in DS infants. The basis of
      the association between DS and leukemia is unknown, but we and others have
      hypothesized that it may be influenced by the mechanism of origin of the extra
      chromosome. Therefore, we initiated a cytogenetic and molecular study of
      nondisjunction in leukemia DS individuals. To date, we have obtained blood and/or
      tissue samples from 55 individuals consisting of 17 cases with TL, 7 cases of
      acute nonlymphocytic leukemia subtype M7 (ANLL-M7, or acute megakaryoblastic
      leukemia, postulated to be related to TL), and 31 cases of other forms of
      leukemia. Analysis of these cases suggests differences between DS children with
      TL and those with other types of leukemia or DS individuals with no history of
      leukemia. Specifically, the TL and ANLL-M7 cases have a highly significant
      increase in the frequency of "atypical" constitutional karyotypes (i.e., mosaic
      trisomies, rings, and/or isochromosomes) and are almost always male.
      Additionally, genetic mapping studies suggest an increase in the frequency of
      disomic homozygosity, especially in proximal 21q, in DS individuals with TL and
      ANLL-M7.

PMID- 7717403
TI  - The 18q- syndrome: analysis of chromosomes by bivariate flow karyotyping and the
      PCR reveals a successive set of deletion breakpoints within 18q21.2-q22.2.
AB  - The 18q- syndrome is one of several terminal deletion disorders that occur in
      humans. Previous G-banding studies suggest that the loss of a critical band,
      18q21.3, results in mental retardation, craniofacial anomalies, and metabolic
      defects. However, it is difficult to reconcile the consistent loss of a single
      region with the large variability in clinical phenotype. The purpose of this
      study was to reassess the extent of chromosomal loss in a cohort of 17 18q-
      syndrome patients by using fluorescent-activated chromosome sorting, PCR, and
      FISH. Bivariate flow karyotypes revealed heterogeneity among the deletions; they
      ranged in size from 9 to 26 Mb. To confirm this heterogeneity at a molecular
      level, deleted and normal chromosomes 18 of six patients were collected by flow
      sorting, preamplified by random priming, and assayed for marker content by the
      PCR. This analysis defined five unique breakpoints among the six patients. We
      conclude that the terminal deletions in the 18q- syndrome occur over a broad
      region spanning the interval from 18q21.2 to 18q22.2. Our results suggest that
      the variability in clinical phenotype may be more representative of a contiguous
      gene syndrome with a baseline deficit of 18q22.2-qter than of the loss of a
      single critical region within 18q21.3.

PMID- 7717404
TI  - A gene for cleidocranial dysplasia maps to the short arm of chromosome 6.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant generalized bone dysplasia
      characterized by mild-to-moderate short stature, clavicular aplasia or
      hypoplasia, supernumerary and ectopic teeth, delayed eruption of secondary teeth,
      a characteristic craniofacial appearance, and a variety of other skeletal
      anomalies. We have performed linkage studies in five families with CCD, with 24
      affected and 20 unaffected individuals, using microsatellite markers spanning two
      candidate regions on chromosomes 8q and 6. The strongest support for linkage was
      with chromosome 6p microsatellite marker D6S282 with a two-point lod score of
      4.84 (theta = .03). Furthermore, the multipoint lod score was 5.70 in the
      interval between D6S282 and D6S291. These data show that the gene for autosomal
      dominant CCD is located within a 19-cM interval on the short arm of chromosome 6,
      between D6S282 and D6S291.

PMID- 7717405
TI  - Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2
      maps to chromosome 1q21-q31.
AB  - The syndrome of hereditary hyperparathyroidism and jaw tumors (HPT-JT) is
      characterized by inheritance, in an autosomal dominant pattern, of recurrent
      parathyroid adenomas, fibro-osseous tumors of the mandible and/or maxilla, Wilms
      tumor, and parathyroid carcinoma. This syndrome is clinically and genetically
      distinct from other endocrine neoplasia syndromes and appears to result from
      mutation of an endocrine tumor gene designated "HRPT2." We studied five HPT-JT
      families (59 persons, 20 affected); using PCR-based markers, we instituted a
      genomewide linkage search after excluding several candidate genes. Lod scores
      were calculated at various recombination fractions (theta), penetrance 90%. We
      mapped HRPT2 to the long arm of chromosome 1 (1q21-q31). The maximal lod score
      was 6.10 at theta = .0 with marker D1S212, or > 10(6) odds in favor of linkage.
      In six hereditary Wilms tumor families (96 persons, 29 affected), we found no
      linkage to 1q markers closely linked with HRPT2 (lod scores -15.6 [D1S191] and 
      17.8 [D1S196], theta = .001). Nine parathyroid adenomas and one Wilms tumor from
      nine members of three HPT-JT families were examined for loss of heterozygosity at
      linked loci. The parathyroid adenomas and Wilms tumor showed no loss of
      heterozygosity for these DNA markers. Our data establish that HRPT2, an endocrine
      tumor gene on the long arm of chromosome 1, is responsible for the HPT-JT
      syndrome but not for the classical hereditary Wilms tumor syndrome.

PMID- 7717407
TI  - Human T-cell receptor V beta gene polymorphism and multiple sclerosis.
AB  - Population-based genetic associations have been reported between RFLPs detected
      with probes corresponding to the genes encoding the beta chain of the T-cell
      receptor for antigen (TCRB) and a variety of autoimmune disorders. In the case of
      multiple sclerosis (MS), these studies have localized a putative disease
      associated gene to a region of approximately 110 kb in length, located within the
      TCRB locus. In the current study, all 14 known TCRBV (variable region) genes
      within the region of localization were mapped and identified. The nucleotide
      sequences of these genes were determined in a panel of six MS patients and six
      healthy controls, who were human-leukocyte antigen and TCRB-RFLP haplotype
      matched. Nine of the 14 TCRBV genes studied showed evidence of polymorphism. PCR
      based assays for each of these polymorphic genes were developed, and allele and
      genotype frequencies were determined in a panel of DNA samples from 48 MS
      patients and 60 control individuals. No significant differences in allele,
      genotype, or phenotype frequencies were observed between the MS patients and
      controls for any of the 14 TCRBV-gene polymorphisms studied. In light of the
      extensive linkage disequilibrium across the region studied, the saturating
      numbers of polymorphisms examined, and the direct sequence analysis of all BV
      genes in the region, these results suggest that it is unlikely that germ-line
      polymorphism in the TCRBV locus makes a major contribution to MS
      susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717408
TI  - Variability of the genetic contribution of Quebec population founders associated
      to some deleterious genes.
AB  - Relatively high frequencies of some rare inherited disorders can be found in the
      Saguenay Region (Quebec). To understand this phenomenon, a research project on
      the 17th-century founder effect that led to the formation of French Canadians'
      gene pool is being carried out. The focus of this study is on founders who
      contributed to the Saguenay gene pool and who are related to contemporary
      probands suffering from any one of five hereditary diseases: cystic fibrosis,
      tyrosinemia, hemochromatosis, Charlevoix-Saguenay spastic ataxia, and
      sensorimotor polyneuropathia with or without agenesis of the corpus callosum. A
      control group has been added for comparison purposes. Altogether, 545 ascending
      genealogies have been reconstructed, using the Interuniversity Institute for
      Population Research's RETRO database, leading to > 2,500 founders. The genetic
      contribution of each founder to each group has been measured. Results show that
      (1) nearly 80% of the individuals' gene pool come from founders who settled in
      Nouvelle-France in the 17th century, whatever the group; (2) 15% of the founders
      explain 90% of the total genetic contribution of the founders, but this pattern
      varies from one group to another; (3) there is no subgroup of founders more
      related to any given group of individuals.

PMID- 7717406
TI  - Y chromosomal DNA variation and the peopling of Japan.
AB  - Four loci mapping to the nonrecombining portion of the Y chromosome were
      genotyped in Japanese populations from Okinawa, the southernmost island of Japan;
      Shizuoka and Aomori on the main island of Honshu; and a small sample of
      Taiwanese. The Y Alu polymorphic (YAP) element is present in 42% of the Japanese
      and absent in the Taiwanese, confirming the irregular distribution of this
      polymorphism in Asia. Data from the four loci were used to determine genetic
      distances among populations, construct Y chromosome haplotypes, and estimate the
      degree of genetic diversity in each population and on different Y chromosome
      haplotypes. Evolutionary analysis of Y haplotypes suggests that polymorphisms at
      the YAP (DYS287) and DXYS5Y loci originated a single time, whereas restriction
      patterns at the DYS1 locus and microsatellite alleles at the DYS19 locus arose
      more than once. Genetic distance analysis indicated that the Okinawans are
      differentiated from Japanese living on Honshu. The data support the hypotheses
      that modern Japanese populations have resulted from distinctive genetic
      contributions involving the ancient Jomon people and Yayoi immigrants from Korea
      or mainland China, with Okinawans experiencing the least amount of admixture with
      the Yayoi. It is suggested that YAP+ chromosomes migrated to Japan with the Jomon
      people > 10,000 years ago and that a large infusion of YAP- chromosomes entered
      Japan with the Yayoi migration starting 2,300 years ago. Different degrees of
      genetic diversity carried by these two ancient chromosomal lineages may be
      explained by the different life-styles (hunter-gatherer versus agriculturalist).
      of the migrant groups, the size of the founding populations, and the antiquities
      of the founding events.

PMID- 7717409
TI  - Demographic history of India and mtDNA-sequence diversity.
AB  - The demographic history of India was examined by comparing mtDNA sequences
      obtained from members of three culturally divergent Indian subpopulations
      (endogamous caste groups). While an inferred tree revealed some clustering
      according to caste affiliation, there was no clear separation into three
      genetically distinct groups along caste lines. Comparison of pairwise nucleotide
      difference distributions, however, did indicate a difference in growth patterns
      between two of the castes. The Brahmin population appears to have undergone
      either a rapid expansion or steady growth. The low-ranking Mukri caste, however,
      may have either maintained a roughly constant population size or undergone
      multiple bottlenecks during that period. Comparison of the Indian sequences to
      those obtained from other populations, using a tree, revealed that the Indian
      sequences, along with all other non-African samples, form a starlike cluster.
      This cluster may represent a major expansion, possibly originating in southern
      Asia, taking place at some point after modern humans initially left Africa.

PMID- 7717410
TI  - Association of attention-deficit disorder and the dopamine transporter gene.
AB  - Attention-deficit hyperactivity disorder (ADHD) has been shown to be familial and
      heritable, in previous studies. As with most psychiatric disorders, examination
      of pedigrees has not revealed a consistent Mendelian mode of transmission. The
      response of ADHD patients to medications that inhibit the dopamine transporter,
      including methylphenidate, amphetamine, pemoline, and bupropion, led us to
      consider the dopamine transporter as a primary candidate gene for ADHD. To avoid
      effects of population stratification and to avoid the problem of classification
      of relatives with other psychiatric disorders as affected or unaffected, we used
      the haplotype-based haplotype relative risk (HHRR) method to test for association
      between a VNTR polymorphism at the dopamine transporter locus (DAT1) and DSM-III
      R-diagnosed ADHD (N = 49) and undifferentiated attention-deficit disorder (UADD)
      (N = 8) in trios composed of father, mother, and affected offspring. HHRR
      analysis revealed significant association between ADHD/UADD and the 480-bp DAT1
      allele (chi 2 7.51, 1 df, P = .006). When cases of UADD were dropped from the
      analysis, similar results were found (Chi 2 7.29, 1 df, P = .007). If these
      findings are replicated, molecular analysis of the dopamine transporter gene may
      identify mutations that increase susceptibility to ADHD/UADD. Biochemical
      analysis of such mutations may lead to development of more effective therapeutic
      interventions.

PMID- 7717412
TI  - New heritable fragile site with spontaneous expression at 1q41.
AB  - The report presents a family ascertained through recurrent spontaneous abortions
      in which a new heritable fragile site located at 1q41 is segregating. The fragile
      site is present in the mother and her son. It is expressed spontaneously in 100%
      of the metaphases from lymphocyte culture using standard conditions. The use of
      folate deficient medium and the addition of FUdR to the medium did not affect the
      appearance nor the level of expression of the fragile site.

PMID- 7717411
TI  - Deletion mapping of X-linked mixed deafness (DFN3) identifies a 265-525-kb region
      centromeric of DXS26.

PMID- 7717413
TI  - Syndrome of proximal interstitial deletion 4p15: report of three cases and review
      of the literature.
AB  - We report on two boys and a girl with interstitial deletion in the short arm of
      chromosome 4 including the segment p15.2p15.33. All had normal growth with
      psychomotor retardation, multiple minor congenital anomalies, and a
      characteristic face distinct from that of the Wolf-Hirschhorn syndrome. One of
      the patients had congenitally enlarged penis. These patients resemble some of the
      previously reported patients with similar cytogenetic abnormalities and suggests
      the recognition of a specific clinical chromosome deletion syndrome.

PMID- 7717414
TI  - Deletion of chromosome 2q24-q31 causes characteristic digital anomalies: case
      report and review.
AB  - We describe a newborn boy with multiple anomalies, including bilateral split foot
      and an interstitial deletion of chromosome 2 (q24.2-q31.1). Four additional cases
      in 2 families involving similar deletions have been reported. Bilateral digital
      anomalies of hands and feet were seen in all 5 cases, including a wide cleft
      between the first and second toes, wide halluces, brachysyndactyly of the toes,
      and camptodactyly of the fingers. Other common manifestations have included
      postnatal growth and mental retardation, microcephaly, down-slanting palpebral
      fissures, micrognathia, and apparently low-set ears. Bilateral digital anomalies
      were reported in 22 of 24 cases with deletions including at least part of region
      2q24-q31. Digital anomalies were not prevalent in 18 patients with deletions of
      chromosome 2q not overlapping 2q24-q31. 2q31.1 appears to be the common deleted
      segment in all cases with significant digital anomalies, which implies the
      existence of one or more genes involved in distal limb morphogenesis in this
      region. HOXD13 and EVX2, located in the proximity of 2q31, were not deleted in
      our patient by Southern analysis. Bilateral digital malformations of the hands
      and feet associated with other anomalies should be evaluated by chromosome
      analysis focused at the 2q24-q31 region.

PMID- 7717415
TI  - Interstitial deletions 4q21.1q25 and 4q25q27: phenotypic variability and relation
      to Rieger anomaly.
AB  - We describe clinical and chromosomal findings in two patients with del(4q).
      Patient 1, with interstitial deletion (4)(q21.1q25), had craniofacial and
      skeletal anomalies and died at 8 months of hydrocephalus. Patient 2, with
      interstitial deletion (4)(q25q27), had craniofacial and skeletal anomalies with
      congenital hypotonia and developmental delay. These patients shared certain
      manifestations with other del(4q) patients but did not have Rieger anomaly.
      Clinical variability among patients with interstitial deletions of 4q may be
      related to variable expression, variable deletion, or imprinting of genes within
      the 4q region.

PMID- 7717416
TI  - Paracentric inversions in humans: a review of 446 paracentric inversions with
      presentation of 120 new cases.
AB  - We present a large review of 446 cases of paracentric inversions (PAI), including
      120 new cases, to assess their incidence, distribution, inheritance, modes of
      ascertainment, interchromosomal effects, viable recombinant offspring, and
      clinical relevance. All 23 autosomes and sex chromosomes had inversions. However,
      none were identified in chromosome arms 18p, 19q, 20q, and Yp. PAI were most
      commonly reported in chromosomes 1, 3, 5, 6, 7, 11, and 14 and less frequently in
      chromosomes 4, 16, 17, 18, 19, 20, 21, 22, and Y. Inversions were most common in
      chromosome arms 6p, 7q, 11q, and 14q and observed least in chromosome arms 2p,
      2q, 3q, 4q, and 6q. Frequently encountered breakpoints included 3(p13p25),
      6(p12p23), 6(p12p25), 7(q11q22), and 11(q21q23). Ascertainment was primarily
      incidental (54.5%), mental retardation and/or congenital anomalies (22.2%),
      spontaneous abortions (11.4%), associations with syndromes (3.0%), and
      infertility (2.0%) accounted for the remainder. Ascertainment was neither related
      to the length of the inverted segment nor to specific inversions except for PAI
      of Xq which often presented with manifestations of Ullrich-Turner syndrome. Sixty
      six percent of PAI were inherited while 8.5% were de novo. Recombination was
      observed in 17 cases, 15 of which resulted in a monocentric chromosomal deletion
      or duplication. No common factors were identified that suggested a tendency
      towards recombination. The incidence of viable recombinants was estimated to be
      3.8%. This review documents that PAI are perhaps more commonly identified than
      suggested in previous reviews. Despite the possible bias of ascertainment in some
      cases, there may be associated risks with PAI that require further examination.
      Our data suggest that PAI carriers do not appear to be free of risks of
      abnormalities or abnormal progeny and caution is recommended when counseling.

PMID- 7717417
TI  - Nutritional patterns of mothers of children with neural tube defects in
      Newfoundland.
AB  - In an exploratory study of the genetic epidemiology of neural tube defects in
      Newfoundland, we studied mothers who had given birth to a child with a neural
      tube defect (NTD) with respect to their nutrition, as well as various other
      factors. The frequency of NTD in the area studied was 3.5/1,000 births and has
      not decreased recently, as it has in some other parts of the world. Twenty-five
      mothers of children with NTD and a comparison group (CG), matched for age and
      neighbourhood, completed 3 day dietary records. The NTD group consisted of all
      mothers who had given birth to an NTD child within the previous 3.5 years in the
      chosen area. The CG mothers were ascertained through the local public health
      nurse who chose the nearest unaffected child born in the same time period as the
      NTD probands. NTD mothers were younger, heavier, and of lower socioeconomic
      status than were CG mothers. CG group women consumed more vitamin supplements
      during the periconceptional period (P < 0.05) and consumed more dairy and cereal
      products, fruits and vegetables (other than potatoes), and fewer sweets than did
      NTD mothers. Sixty-four percent of NTD mothers had folacin intakes below the
      recommended level (168 mg) compared to 27% of CG mothers (P < 0.01). These
      findings support previous evidence that poor maternal nutrition, and low dietary
      folate in particular, increase the chance of having a child with an NTD, and
      emphasize the need for supplementary folate in the diet of women of childbearing
      age in areas where the frequency of NTDs is high.

PMID- 7717418
TI  - Craniodigital syndromes: report of a child with Filippi syndrome and discussion
      of differential diagnosis.
AB  - We describe a boy with low birth weight, congenital microcephaly, multiple minor
      facial anomalies, cleft palate, soft tissue syndactyly of fingers and toes, and
      moderate to severe mental retardation. Literature review suggested 6 possible
      diagnoses, including Scott craniodigital syndrome, Chitayat syndrome, Filippi
      syndrome, Zerres syndrome, Kelly syndrome, and Woods syndrome. Each has as part
      of the phenotype craniofacial anomalies and soft tissue syndactyly of fingers and
      toes; and superficially, distinction among the 6 may be difficult. However, based
      on the phenotype analysis we performed, we conclude that our patient has Filippi
      syndrome, and thus is the first reported case from the United States.

PMID- 7717419
TI  - Dominant mesomelic shortness of stature with acral synostoses, umbilical
      anomalies, and soft palate agenesis.
AB  - We report on a father and 2 children (a living 4-year-old girl and an aborted 18
      week-old fetus) with a dominantly inherited form of mesomelic shortness of
      stature with severe ankle, knee, and elbow involvement. Skeletal abnormalities
      included brachymetacarpy and brachymetatarsy of the 3rd to 5th rays, synostoses
      in these bones, synostoses of metacarpals and metatarsals II to V with the
      corresponding carpal/tarsal bones, partial fusion in the proximal row of carpal
      bones, and mild vertebral anomalies. Father and daughter also had downslanted
      palpebral fissures, beaked nose, hypertelorism, ptosis, microretrognathia, and
      transverse agenesis of the soft palate. Abnormally short umbilical cord with
      unusually long skin coverage was present. Mesomelic shortness worsens with time,
      with progressive curvature of the forearm. This condition appears to represent a
      previously undescribed MCA/dysostosis syndrome.

PMID- 7717420
TI  - Distal aphalangia, syndactyly, and extra metatarsal, associated with short
      stature, microcephaly, and borderline intelligence: a new autosomal dominant
      disorder.
AB  - We report on 3 members of a Spanish family with partial aphalangia, syndactyly
      with duplication of metatarsal IV, microcephaly, dull intelligence, and short
      stature. The MCA pattern observed in this family appears to constitute a
      previously undescribed syndrome.

PMID- 7717421
TI  - Skeletal manifestations in Fryns syndrome.
AB  - We report on a female baby with Fryns syndrome who died soon after birth. The
      patient had short limbs, coarse face, hypoplastic lungs, diaphragmatic hernia,
      and acral hypoplasia. Literature review disclosed varying degrees of skeletal
      manifestations in Fryns syndrome; short limbs may be a component of Fryns
      syndrome.

PMID- 7717422
TI  - Interstitial duplication of proximal 22q: phenotypic overlap with cat eye
      syndrome.
AB  - We describe a child with downslanting palpebral fissures, preauricular
      malfunctions, congenital heart defect (total anomalous pulmonary venous return),
      unilateral absence of a kidney, and developmental delay with an apparent
      interstitial duplication of proximal 22q. Fluorescent in situ hybridization
      (FISH) analysis showed duplication of the IGLC locus, and C-banding of the
      duplicated region was negative. The duplication appears to involve 22q11.2-q12.
      Although the child has neither colobomas nor microphthalmia, he shows phenotypic
      overlap with the cat eye syndrome, which is caused by a supernumerary
      bisatellited chromosome arising from inverted duplication of the short arm and
      proximal long arm of chromosome 22. Further molecular studies of this patient
      should help to define the regions responsible for the manifestations of cat eye
      syndrome.

PMID- 7717423
TI  - Discordant fibular aplasia in twins.
AB  - A male infant, one of monozygotic twins, was born with absence of fibulae,
      ectrodactyly of the right hand and both feet, with accompanying deficiencies.
      This second case report of a discordant fibular aplasia developmental field
      defect occurring in monozygotic twins, although likely sporadic, is interesting
      because of the similar pattern of anomalies.

PMID- 7717424
TI  - Trisomy 2p: analysis of unusual phenotypic findings.
AB  - We present three probands with partial trisomies 2p21-23 due to
      ins(4;2)(q21;p21p23) pat, 2p23-pter due to t(2;4)(p23;q35)mat, and 2p21-pter due
      to t(2;11)(p21;q23.3)mat. More than 50 cases of partial trisomy 2p have been
      reviewed and some abnormalities, unusual for most other types of structural
      autosomal imbalance, have been found in patients with inherited forms of 2p
      trisomy and in their non-karyotyped sibs. Neural tube defects (anencephaly,
      occipital encephalocele, and spina bifida) were found in five probands and 4/6
      affected non-karyotyped sibs. The only triplicated segment common to all was
      2p24. Different forms of "broncho-pulmonary a/hypoplasia" (including two cases of
      lung agenesis) were described in four patients (overlapping triplicated segment
      was 2p21-p25). Three patients (with overlapping triplicated segment 2p23-p25) had
      diaphragmatic hernia. Abnormal rotation of the heart or L-transposition of large
      vessels (with or without visceral heterotaxia) was found in two infants
      (overlapping triplicated segment 2p23-p24). In two patients with common
      triplicated segment 2p22.3-p25, neuroblastoma has been described. The occurrence
      of all these defects may be explained either by the action of the same gene(s)
      mapped to 2p24 or by action of some independent factors located in different
      segments of the short arm. Although the latter hypothesis is much less probable,
      it can not be rejected at the present time. We propose the existence of a genetic
      system controlling surveillance of an abnormal embryo to explain the phenotypic
      differences between patients with the same imbalance within a family. In some
      "restrictive" combinations the abnormal embryos will die, although in
      "permissive" combinations they can survive.

PMID- 7717425
TI  - Satellited 4q identified in amniotic fluid cells.
AB  - Extra material was identified on the distal long arm of a chromosome 4 in an
      amniotic fluid specimen sampled at 16.6 weeks of gestational age. There was no
      visible loss of material from chromosome 4, and no evidence for a balanced
      rearrangement. The primary counseling issue in this case was advanced maternal
      age. Ultrasound findings were normal, and family history was unremarkable. The
      identical 4qs chromosome was observed in cells from a paternal peripheral blood
      specimen and appeared to be an unbalanced rearrangement. This extra material was
      NOR positive in lymphocytes from the father, but was negative in the fetal
      amniocytes. Father's relatives were studied to verify the familial origin of this
      anomaly. In situ hybridization with both exon and intron sequences of ribosomal
      DNA demonstrated that ribosomal DNA is present at the terminus of the 4qs
      chromosome in the fetus, father, and paternal grandmother. This satellited 4q
      might have been derived from a translocation event that resulted in very little
      or no loss from the 4q and no specific phenotype. This derivative chromosome 4
      has been inherited through at least 3 generations of phenotypically normal
      individuals.

PMID- 7717426
TI  - Developmental anomalies suggestive of the human homologue of the mouse mutant
      disorganization.
AB  - We describe a 21-week-old fetus with a pattern of multiple congenital anomalies
      suggestive of the human homologue of the mouse mutant disorganization (Ds).
      Manifestations included facial asymmetry, thick eye brows, micrognathia,
      apparently lowset ears, an enormous abdominal wall defect, severe kyphoscoliosis,
      camptodactyly of the fingers, complete absence of the left lower limb, and
      absence of the lower part of the sacrum and coccyx, as well as left side of the
      pelvis. There was a disorganized appearance of the right foot with supernumerary
      digits and appendages and talipes equinovarus. No obvious amniotic bands or
      oligohydramnios were noted. Similar cases in the literature are reviewed and the
      clinical significance to genetic counselling is emphasized.

PMID- 7717427
TI  - Synpolydactyly (type II syndactyly) with aplasia/hypoplasia of the middle
      phalanges of the toes: report on a family with eight affected members in four
      generations.
AB  - We describe a new family with synpolydactyly (syndactyly type II) with 8 affected
      members in 4 generations. Aplasia/hypoplasia of the middle phalanges of the toes
      was also noted. In our opinion, this anomaly represents a frequent manifestation
      of synpolydactyly. No other major skeletal or extraskeletal malformations were
      present.

PMID- 7717429
TI  - Delays in diagnosis in children with sacral anomalies.

PMID- 7717428
TI  - Prenatal diagnosis of the urea cycle diseases: a survey of the European cases.
AB  - A European survey of prenatal diagnosis cases involving urea cycle diseases was
      performed. Citrullinemia was the most frequently investigated disease (108
      cases). Other diseases are, in order of frequency, argininosuccinic aciduria (75
      cases), ornithine transcarbamylase defect (52 cases), carbamoylphosphate
      synthetase defect (8 cases), triple H (3 cases), and arginase deficiency (1
      case). Only one disease (ornithine transcarbamylase defect) is presently
      diagnosed using molecular biology methods.

PMID- 7717430
TI  - Med errors. Potassium perils.

PMID- 7717431
TI  - Boob tube strikes again?

PMID- 7717432
TI  - Never discourage hope.

PMID- 7717433
TI  - Using the fentanyl patch.

PMID- 7717434
TI  - Nursing in the right words.

PMID- 7717435
TI  - Reaching out to the suicidal patient.

PMID- 7717436
TI  - The nursing life: something rubbed off on Lisa.

PMID- 7717437
TI  - Clinical snapshot: glaucoma.

PMID- 7717438
TI  - How to manage common arrhythmias in medical patients.

PMID- 7717440
TI  - Emergency! Quick response to hypothermia and frostbite.

PMID- 7717439
TI  - Designing an effective clinical pathway for stroke.

PMID- 7717441
TI  - When a child dies.

PMID- 7717442
TI  - Discomfort over a 'death sentence'.

PMID- 7717443
TI  - 'Dejobbing' the workplace.

PMID- 7717444
TI  - 'You're not rude, you're an angel'.

PMID- 7717445
TI  - Cellular kinetics in the lungs of aging Fischer 344 rats after acute exposure to
      ozone.
AB  - Lung repair in aging Fischer 344 male rats was investigated after an acute
      inhalation exposure to ozone. Adult (9-month-old) and senescent (24-month-old)
      rats were exposed to 0.8 ppm ozone for a single period of 6 hours, and thereafter
      studied over 5 days of recovery in clean air. The animals were given
      intraperitoneal injections of colchicine and [3H]thymidine, 4 hours and 1.5 hours
      before termination, respectively. The lungs were inflated with glutaraldehyde,
      and tissue samples were embedded in epoxy resin for electron microscopy, or in
      glycol methacrylate for light-microscopic autoradiography. Exposure to ozone
      produced epithelial injury in alveolar ducts and terminal bronchioles, later
      reflected by the transient increase in mitotic activity of nonciliated
      bronchiolar cells and alveolar type 2 cells. The increase in metaphase-arrested
      cells and [3H]thymidine-labeled cells in bronchioles followed similar time
      courses, ie, maximal at days 1.5 to 2, and subsiding by day 3. In the alveoli,
      type 1 cell necrosis was observed early after exposure (6 hours recovery),
      without notable structural changes in the interstitial and endothelial
      compartments. The increased mitotic activity in the alveolar septa was mostly due
      to proliferation of epithelial type 2 cells, which was maximal at day 1.5, and of
      interstitial cells, maximal at day 2.5. The magnitude of the mitotic responses of
      nonciliated bronchiolar cells, alveolar type 2 cells and interstitial cells was
      highest (+50%) in the lungs of senescent rats. Although the cellular events
      during repair are essentially similar in both age groups, the results indicate
      that senescent rats have a significantly higher level of initial injury from
      inhalation of ozone than adult animals.

PMID- 7717446
TI  - Pulmonary alveolar proteinosis. A spontaneous and inducible disease in
      immunodeficient germ-free mice.
AB  - Spontaneous pulmonary alveolar proteinosis (PAP), which resembles human PAP, was
      found in aging (35 to 40 weeks) germ-free SCID-beige (scid/scid-bg/bg) mice.
      Spontaneous PAP was not observed in germ-free SCID mice. We describe the
      induction of PAP in SCID mice monoassociated with a pure culture of Candida
      albicans for 15 to 40 weeks. The gastrointestinal tracts only are colonized, and
      disseminated or pulmonary candidiasis does not occur. Another spontaneous form of
      PAP, designated type II, was discovered in germ-free beige (bg/bg and bg/+) mice
      and in beige-nude (bg/bg-nu/nu) mice. In this form of PAP, macrophages appear to
      be unable to digest the ingested phospholipoprotein complex and then accumulate
      in the alveolar spaces. These murine models should prove useful in elucidating
      the relationships between immune deficiencies, infections, and cytokine
      regulation of granulocyte and macrophage production and function in pulmonary
      alveolar proteinosis.

PMID- 7717448
TI  - Lymphocyte predominance Hodgkin's disease. Evidence for a kappa light chain
      restricted monotypic B-cell neoplasm.
AB  - Over the last decade, it has been noted that nodular lymphocytic and/or
      histiocytic predominance Hodgkin's disease (NLPHD) has clinical, histological,
      and immunophenotypical differences from classical Hodgkin's disease, but it is
      not clear whether NLPHD represents a B-cell neoplasm or merely an unusual B
      lineage reactive condition. We evaluated 36 cases of LPHD (31 nodular, 5 diffuse)
      for evidence of B-cell clonality by immunohistochemistry for light-chain protein
      using polyclonal antibodies and microwave antigen retrieval, and by a highly
      sensitive in situ hybridization technique for light-chain mRNA using 3H-labeled
      antisense RNA probes. We found monotypic light-chain restriction for kappa
      protein in 36% of cases, with no clear predominance for either light-chain
      protein in the other cases. By in situ hybridization, 80% of the evaluable cases
      showed clear evidence of light-chain monotypsim, with 96% of cases monotypic for
      kappa mRNA and one case monotypic for lambda mRNA. In virtually all of these
      cases, the L&H cells were found to be monotypic, consistent with monoclonality.
      In about one-half of these cases, a small lymphocytic component was also found to
      be monotypic. Our data support the hypothesis that NLPHD and its rare diffuse
      variant represent a monotypic B-cell neoplasm, almost always of kappa light-chain
      type. NLPHD represents a neoplasm distinct from classical Hodgkin's disease.

PMID- 7717449
TI  - Selective blockade of the endothelin subtype A receptor decreases early
      atherosclerosis in hamsters fed cholesterol.
AB  - Recent studies suggest that endothelin and its receptors may be involved in
      atherogenesis. To test this hypothesis, cholesterol-fed hamsters were treated
      with a selective endothelin subtype A (ETA) receptor antagonist BMS-182874.
      Characterization of hamster atherosclerotic plaques indicated that they contained
      a fibrous cap of smooth muscle cells, large macrophage-foam cells, and epitopes
      of oxidized low density lipoprotein. Messenger RNA for both ETA and ETB receptors
      was detected in aortic endothelial cells, in medial smooth muscle cells, and in
      macrophage-foam cells and smooth muscle cells of the fibro-fatty plaques. BMS
      182874 inhibited the endothelin-1-induced pressor response whereas the depressor
      effect was unaltered, suggesting that vascular ETA receptors were selectively
      blocked in vivo. In hyperlipidemic hamsters, BMS-182874 decreased the area of the
      fatty streak by reducing the number and size of macrophage-foam cells. The
      results indicated that ETA receptors and thus endothelin promoted the early
      inflammatory phase of atherosclerosis.

PMID- 7717447
TI  - Etiology and pathogenesis of prion diseases.

PMID- 7717450
TI  - Analysis of the neurofibromatosis 2 gene reveals molecular variants of
      meningioma.
AB  - There is evidence from cytogenetic and loss of heterozygosity studies for the
      involvement of a tumor suppressor gene on chromosome 22 in the formation of
      meningiomas. Recently, the NF2 gene, which causes neurofibromatosis type 2 and
      which is located in the affected region on chromosome 22, has been identified. A
      previous study on 8 of the 17 exons of the NF2 gene described mutations in 16% of
      meningiomas. We have analyzed the entire coding region of the NF2 gene in 70
      sporadic meningiomas and identified 43 mutations in 41 patients. These resulted
      predominantly in immediate truncation, splicing abnormalities, or an altered
      reading frame of the predicted protein product. Although there was no evidence
      for distinct hotspots, all mutations occurred in the first 13 exons, the region
      of homology with the filopodial proteins moesin, ezrin, and radixin. The
      association of loss of heterozygosity on chromosome 22 with mutations in the NF2
      gene was significant. These data suggest that NF2 represents the meningioma locus
      on chromosome 22. NF2 mutations occurred significantly more frequently in
      fibroblastic meningioma (70%) and transitional meningioma (83%) than in
      meningiothelial meningioma (25%), thus indicating a differential molecular
      pathogenesis of these meningioma variants.

PMID- 7717452
TI  - The lysosomal cysteine protease, cathepsin S, is increased in Alzheimer's disease
      and Down syndrome brain. An immunocytochemical study.
AB  - Expression of cathepsin (cat) S, a lysosomal cysteine protease, has recently been
      shown to cause an increase in production of amyloid beta-peptides in transfected
      human cells. In this study, we examined the presence and localization of cat S by
      immunocytochemistry in 21 control, 24 Alzheimer's disease (AD), and 10 Down
      syndrome (DS) postmortem brains. An antiserum to a human cat S fusion protein was
      affinity purified and its specificity confirmed by abolition of immunoreactivity
      after adsorption with cat S but not cat L fusion protein. A small minority of
      control cases showed light, focal staining of scattered cortical neurons. Many
      control cases, as well as most AD and DS cases, showed prominent staining of
      vascular smooth muscle cells, particularly in leptomeningeal vessels. Both AD and
      DS brain tissue showed increased immunoreactivity in a subset of neocortical and
      hippocampal neurons and glia. Cat S immunoreactivity occurred in a granular,
      cytoplasmic pattern in some neurons or in a more dense staining pattern in
      certain neurofibrillary tangle-bearing neurons. Cat S-positive neurons were also
      present in amygdala and basal forebrain in AD brains. A subset of astrocytes were
      immunoreactive with the cat S antibody in AD and DS but not in control brains. In
      rare AD cases, cat S immunostaining was observed in astrocytes in the periphery
      of amyloid-beta-containing plaques. These results suggest that cat S is up
      regulated in AD and DS brain. The association of cat S immunoreactivity with
      tangle-bearing neurons, astrocytes, and rare senile plaques implies a role for
      altered cat S activity in the pathogenesis of AD.

PMID- 7717453
TI  - Epstein-Barr virus in primary gastrointestinal T cell lymphomas. Association with
      gluten-sensitive enteropathy, pathological features, and immunophenotype.
AB  - Forty-three primary gastrointestinal T cell lymphomas were investigated for the
      presence of Epstein-Barr virus (EBV) by polymerase chain reaction, RNA in situ
      hybridization, and immunohistochemistry. In addition, the association between EBV
      and clinicopathological characteristics of these lymphomas was investigated. Five
      of the thirty-eight cases that could be evaluated expressed EBV-encoded
      nonpolyadenylated RNA-1 in most tumor cells. Two of these five cases were EBV
      latent membrane protein-1 positive. All five cases were CD30 positive. In three
      of these five EBV-associated T cell lymphomas, the tumor cells were considered to
      be the neoplastic counterparts of activated cytotoxic T cells as shown by the
      expression of granzyme B. There was no association with histological
      characteristics of gluten-sensitive enteropathy, angioinvasion, necrosis,
      eosinophilia, or epitheliotropism of the tumor cells. The substantial percentage
      (58%) of EBV DNA polymerase chain reaction-positive cases was largely the result
      of the presence of EBV-encoded RNA-1-positive reactive cells. In conclusion, EBV
      might have an important etiological role in only 13% of the primary
      gastrointestinal T cell lymphomas. This percentage is similar to the findings in
      primary lymph node and lung T cell lymphomas.

PMID- 7717451
TI  - IGF2 expression is a marker for paraganglionic/SIF cell differentiation in
      neuroblastoma.
AB  - Neuroblastoma is a childhood tumor of the sympathetic nervous system.
      Observations in the Beckwith-Wiedemann syndrome suggest that sympathetic
      embryonal cells with an abundant expression of the insulin-like growth factor 2
      gene (IGF2) may be involved in the genesis of low-malignant infant
      neuroblastomas. We have therefore compared the cell type-specific IGF2 expression
      of the human sympathetic nervous system during early development with that of
      neuroblastoma. An abundant expression in normal sympathetic tissue was specific
      to extra-adrenal chromaffin cells, ie, paraganglia and small intensely
      fluorescent (SIF) cells, whereas sympathetic neuronal cells were IGF2-negative. A
      subpopulation of neuroblastomas expressed IGF2, which correlated with an early
      age at diagnosis, an extra-adrenal tumor origin, and severe hemodynamic signs of
      catecholamine secretion. Histologically IGF2-expressing tumors displayed a
      lobular growth pattern, and expression was restricted to the most mature and
      least proliferative cells. Typically, these cells were morphologically and
      histochemically similar to paraganglia/SIF cells and formed distinct ring-like
      zones in the center of the lobules around a core of apoptosis-like tumor cells.
      The similarities found between IGF2-expressing neuroblastoma cells and
      paraganglia/SIF cells in terms of histological features, anatomical origin, and
      age-dependent growth suggest a paraganglionic/SIF cell lineage of most infant
      tumors and also of extra-adrenal tumors diagnosed after infancy. Furthermore,
      since paraganglia/SIF cells undergo postnatal involution, the same cellular
      mechanism may be responsible for spontaneous regression in infant neuroblastoma.

PMID- 7717454
TI  - Modulation of JE/MCP-1 expression in dermal wound repair.
AB  - The tissue macrophage plays a prominent role in wound repair, yet the parameters
      that influence macrophage migration into the wound bed are not well understood.
      To better understand the process of macrophage recruitment, the production of JE,
      the murine homologue of monocyte chemoattractant protein 1(JE/MCP-1), was
      examined in a murine model of dermal wound repair. High levels of JE/MCP-1 mRNA
      were found in dermal punch wounds at 12 hours and 1 day (24 hours) after
      wounding; mRNA levels slowly decreased to undetectable by day 21. In situ
      hybridization analysis of wounds revealed that JE/MCP-1 was predominantly
      expressed by monocytic and macrophage-like cells, as well as by occasional
      fibroblasts and other interstitial cells. To correlate JE/MCP-1 production with
      macrophage migration, macrophage infiltration into the wound bed was quantitated.
      The number of macrophages within the wound increased to a maximum at day 3 (11.3
      +/- 4.5 macrophages per high power field), began to decrease at day 5 (4.8 +/-
      1.9 macrophages per high power field), and reached near base line at day 10 (3.0
      +/- 1.1 macrophages per high power field). The results demonstrate that JE/MCP-1
      production within wounds is closely linked to the time course and distribution of
      macrophage infiltration, with maximal JE/MCP-1 mRNA levels occurring 1 to 2 days
      before maximal macrophage infiltration. The results support a role for JE/MCP-1
      in the recruitment of wound macrophages and suggest that macrophages, through the
      production of JE/MCP-1, may sustain the recruitment of additional monocytes and
      macrophages into sites of injury.

PMID- 7717455
TI  - Proliferative potential and p53 overexpression in precursor and early stage
      lesions of bronchioloalveolar lung carcinoma.
AB  - To elucidate the pathogenesis of bronchioloalveolar lung carcinoma (BAC), we
      evaluated the lesion size, growth fraction, and p53 overexpression of atypical
      adenomatous hyperplasia (AAH) and early stage BAC. AAH was classified as showing
      low grade or high grade atypia. AAH-like carcinoma, presumably very early stage
      BAC, was distinguished from AAH in that it exhibited remarkable atypia suggestive
      of malignant potential and from overt BAC in that it lacked unequivocal malignant
      features, including invasive/destructive growth. The growth fraction was
      determined immunohistochemically in terms of the Ki-67 labeling index. The
      overexpression of p53 was evaluated by assessing the nuclear accumulation of
      immunoreactive p53 protein. Both the lesion size and the growth fraction
      increased from low grade AAH, to high grade AAH, to AAH-like carcinoma, and to
      overt adenocarcinoma. The overexpression of p53 in AAH-like carcinoma was similar
      to that in overt adenocarcinoma and was more frequent than that in AAH. Our
      findings indicate that AAH, AAH-like carcinoma, and overt BAC represent different
      categories, although the cellular events occurring in these lesions presumably
      represent a continuous spectrum of the changes that are reflected in the
      cytomorphology and lesion size. The findings here suggest that AAH and AAH-like
      carcinomas constitute a population of heterogeneous lesions representing
      different steps toward overt BAC.

PMID- 7717456
TI  - Improved engraftment of human spleen cells in NOD/LtSz-scid/scid mice as compared
      with C.B-17-scid/scid mice.
AB  - T and B lymphocyte-deficient mice homozygous for the severe combined
      immunodeficiency (SCID) mutation can be immunologically engrafted with human
      lymphocytes. However, low levels of human peripheral blood mononuclear cell
      engraftment are commonly observed, impeding full use of this model. We now
      demonstrate that strain background in mice homozygous for the scid mutation is a
      strong determinant of levels of human lymphocyte engraftment. NOD/LtSz-scid/scid
      mice support higher levels of engraftment of both human spleen and peripheral
      blood mononuclear cells than do C.B-17-scid/scid mice. We observed, using human
      spleen cell injected scid mice, 1), high levels of engraftment of the host
      peripheral lymphoid tissues with human CD45+ (leukocytes), CD3+ (T cells), CD4+
      (helper/inducer), and CD8+ (suppressor/cytotoxic) lymphoid cells for up to 24
      weeks in NOD/LtSz-scid/scid mice; 2), migration of high numbers of human
      lymphocytes to peripheral lymphoid and nonlymphoid organs in NOD/LtSz-scid/scid,
      but not in C.B-17-scid/scid mice; 3), higher levels of serum immunoglobulin of
      human origin in NOD/LtSz-scid/scid mice than in C.B-17-scid/scid mice; 4),
      histological lesions characteristic of human anti-mouse xenoreactivity in
      NOD/LtSz-scid/scid mice; and 5), human origin antibodies against filarial
      antigens after engraftment with native human spleen cells. The use of NOD/LtSz
      scid/scid mice as recipients to achieve significantly enhanced human
      lymphopoietic cell engraftment will now enable human immunity to be more easily
      studied in animal models.

PMID- 7717457
TI  - Spongiotic pericytoma: a benign neoplasm deriving from the perisinusoidal (Ito)
      cells in rat liver.
AB  - Spongiosis hepatis has been known for some time to develop frequently in livers
      of rats and fish treated with hepatocarcinogens and was considered to derive from
      the perisinusoidal (Ito) cells (PSC). Using rat liver treated with N
      nitrosomorpholine at different dose levels, we studied the cellular composition
      and origin as well as the proliferation kinetics of spongiosis hepatis by
      immunohistochemical demonstration of desmin, vimentin, and alpha-smooth-muscle
      actin, and by autoradiographic determination of [3H]-thymidine incorporation,
      respectively. The vast majority of the cells forming spongiosis hepatis were
      positive for desmin and vimentin but negative for alpha-smooth-muscle actin,
      confirming the cellular origin of spongiosis hepatis from PSC. In addition,
      immunohistochemical demonstration of desmin and vimentin revealed that spongiosis
      hepatis is an integral part of larger lesions consisting of focal PSC aggregates.
      These aggregates show a significantly increased incorporation of [3H]-thymidine
      compared with PSC in the extrafocal tissue and in the liver tissue of untreated
      control animals. In stop experiments, this increased labeling index was
      maintained many months after withdrawal of the carcinogen, in line with the
      earlier observation of a progressive behavior of spongiosis hepatis. We conclude
      that PSC may give rise to proliferative lesions appearing as PSC aggregates
      associated with more or less pronounced spongiosis hepatis. The persistence, the
      proliferative activity, and the slow expansive growth of these lesions suggest a
      benign neoplastic behavior. We therefore propose to classify these lesions as
      spongiotic pericytoma. Malignant tumors possibly originating from spongiotic
      pericytoma should consequently by classified as perisinusoidal (Ito) cell
      sarcomas.

PMID- 7717458
TI  - Transfer of neuropathogenic simian immunodeficiency virus with naturally infected
      microglia.
AB  - The central nervous system (CNS) is a target for human immunodeficiency virus
      infection, and, in individuals with acquired immune deficiency syndrome, this can
      lead to a devastating dementia. Only certain viral variants appear capable of
      invading the CNS and infecting microglia and brain macrophages. To determine
      whether the virus entering the brain may be particularly pathogenic to the CNS,
      we isolated microglia from the brains of simian immunodeficiency virus-infected
      rhesus monkeys. Serial transfer of these cells into naive animals indicated that
      productive simian immunodeficiency virus infection could indeed be transferred.
      Furthermore, CNS infection occurred within a relatively short time span and was
      associated with viral gene expression in the brain and pathology characteristic
      of human immunodeficiency virus encephalitis. While demonstrating that
      neuropathogenic variants partition into the CNS, our approach will allow the
      dissection of functional neuropathogenic elements present in these viruses.

PMID- 7717459
TI  - Neurofibrillary degeneration in amyotrophic lateral sclerosis/parkinsonism
      dementia complex of Guam. Immunochemical characterization of tau proteins.
AB  - Neurofibrillary tangles are observed in several neurodegenerative disorders
      including Alzheimer's disease, progressive supranuclear palsy, and amyotrophic
      lateral sclerosis/parkinsonism-dementia complex of Guam. The major components of
      neurofibrillary tangles are hyperphosphorylated tau proteins that can be directly
      detected in brain homogenates, using immunoblotting with specific immunological
      probes. To investigate whether tau proteins differ biochemically among various
      neurodegenerative disorders, we analyzed a series of brain samples from Guamanian
      patients in comparison with Alzheimer's disease, progressive supranuclear palsy,
      and normal aging. In Alzheimer's disease, these hyperphosphorylated tau proteins
      are composed of a triplet referred to as tau 55, 64, and 69, whereas in
      progressive supranuclear palsy, neurofibrillary degeneration is characterized by
      a tau doublet (tau 64 and 69). In the present study, characterization of tau
      proteins was performed by immunoblotting, on different cortical and subcortical
      regions of postmortem brain specimens from Guamanian natives. In all of the
      cases, biochemical data were always consistent with neuropathological findings.
      In contrast to Alzheimer's disease patients where the tau triplet is found mostly
      in cortical regions, a similar triplet was strongly detected in both cortical and
      subcortical areas in Guamanian patients. The tau profile differed quantitatively
      from case to case demonstrating that the Alzheimer's disease-related tau triplet
      had a heterogeneous regional distribution. These data suggest that the tau
      triplet found in amyotrophic lateral sclerosis/parkinsonism-dementia complex of
      Guam is similar to that observed in Alzheimer's disease, and the regional
      distribution of tau proteins differs in these disorders.

PMID- 7717460
TI  - Cellular localization of thrombomodulin in human epithelium and squamous
      malignancies.
AB  - Thrombomodulin is a cell surface glycoprotein that functions as an anticoagulant.
      Although initially identified on endothelial cells, thrombomodulin is also
      expressed by other vascular cells, by mesothelial cells, and by epidermal
      keratinocytes. To determine whether thrombomodulin is expressed by epithelial
      cells in locations other than skin, we conducted a survey of thrombomodulin
      protein and mRNA in human epithelium. Thrombomodulin protein was detected by
      immunohistochemistry in all samples containing stratified squamous epithelium,
      including oral mucosa, larynx, esophagus, uterine ectocervix, and vagina. In
      these tissues, thrombomodulin staining localized to the suprabasal layer, with
      minimal staining observed in the basal or superficial layers of epithelium.
      Thrombomodulin was not detected in cuboidal, simple columnar, or pseudostratified
      columnar epithelium and was detected variably in transitional epithelium.
      Thrombomodulin staining was also observed in 21 of 26 cases of invasive squamous
      cell carcinoma and in several examples of squamous carcinoma-in-situ and squamous
      metaplasia. Expression of thrombomodulin mRNA was confirmed by in situ
      hybridization in both normal and malignant squamous epithelium. Full-length,
      functionally active thrombomodulin was demonstrated in cultured squamous
      epithelial cells. These data demonstrate that thrombomodulin expression
      correlates with the squamous phenotype and suggest that hemostasis is regulated
      by compartmentalization of procoagulant and anti-coagulant epithelial proteins.

PMID- 7717461
TI  - Interleukin-6 and interleukin-6 soluble receptor regulate proliferation of
      normal, human papillomavirus-immortalized, and carcinoma-derived cervical cells
      in vitro.
AB  - A variety of sexually transmitted diseases frequently accompany infection with
      human papillomavirus and stimulate inflammation of the cervical mucosa.
      Inflammation and cell injury cause release of proinflammatory cytokines, which in
      turn might regulate growth of human papillomavirus-infected cells. This study
      compared the interaction of the proinflammatory cytokine, interleukin-6 (IL-6),
      and its soluble receptor with normal ecto- and endocervical cells, human
      papillomavirus-immortalized ectocervical cells, and squamous carcinoma-derived
      cell lines. Proliferation of normal cervical cells was enhanced by IL-6 but
      inhibited by its soluble receptor. However, both IL-6 and its soluble receptor
      significantly stimulated growth of the three immortal and four cervical carcinoma
      derived cell lines analyzed. Stimulation by IL-6 was dose dependent and was
      blocked by an antibody that neutralized IL-6 activity. IL-6-mediated
      proliferation was accompanied by increased expression of RNAs encoding
      transforming growth factor-alpha and amphiregulin, two epidermal growth factor
      receptor ligands. Furthermore, growth stimulation by IL-6 was significantly
      inhibited by antibodies that either blocked signal transduction by the epidermal
      growth factor receptor or that neutralized transforming growth factor-alpha or
      amphiregulin activity. Thus, IL-6 stimulates proliferation of human
      papillomavirus-immortalized cervical cells via an epidermal growth factor
      receptor-dependent pathway involving autocrine stimulation by transforming growth
      factor-alpha and amphiregulin.

PMID- 7717463
TI  - Spontaneous premature chromosome condensation, micronucleus formation, and non
      apoptotic cell death in heated HeLa S3 cells. Ultrastructural observations.
AB  - Hyperthermia is an efficient means of inducing cell death in vivo and in vitro.
      Among human neoplastic cells, HeLa S3 cells are susceptible to heat injury when
      exposed to long duration moderate hyperthermia (41.5 C), conditions that are
      reproducible and sustainable in the clinical setting. Hence, HeLa S3 cells are a
      useful substrate for evaluation of hyperthermic injury in human neoplasia.
      Previous studies have demonstrated a consistent response of HeLa S3 cells to
      moderate hyperthermia: spontaneous premature condensation of chromosomes during
      heat exposure in S phase followed by apparent nuclear fragmentation and,
      inevitably, cell death. To further characterize the morphological features of
      this process, HeLa S3 cells grown in suspension at 37 C were heated for 4, 8, 12,
      or 16 hours at 41.5 C and harvested in glutaraldehyde for electron microscopic
      evaluation. Compared with untreated controls, heated samples exhibited a
      characteristic pattern of chromosome condensation that mimicked mitotic prophase
      but was followed by haphazard asymmetric segregation of chromatid clusters in
      abnormal metaphase/anaphase and premature reformation of nuclear membrane,
      resulting not in nuclear fragmentation, but in multiple micronuclei. This pattern
      of nuclear morphology was not observed in controls. The fraction of cells with
      micronuclear morphology increased with time in heated samples (from 3.6% at 4
      hours to 16.6% at 16 hours), consistent with previous light microscopic analyses
      of nuclear fragmentation. Cells with multiple micronuclei subsequently exhibited
      features similar to necrotic cell death. Apoptosis was never observed. Moderate
      hyperthermia appears to induce a novel morphological pattern of cell injury and
      death in HeLa S3 cell lines that may be useful as a means of screening cell lines
      for nonmorphological analyses of hyperthermic injury.

PMID- 7717462
TI  - Establishment and characterization of two divergent cell lines derived from a
      human chromophobe renal cell carcinoma.
AB  - The chromophobe renal cell carcinoma is a distinct type of renal cancer
      presumably derived from the intercalated cell of the collecting duct system and
      exhibiting a better prognosis than other types of renal cell carcinoma.
      Chromophobe carcinomas can be separated from other types of renal cell carcinoma
      by their characteristic cytomorphology, ultrastructural appearance, cytoskeletal
      architecture, and cytogenetic aberrations. As no permanent cell line of the
      chromophobe tumor type has previously been described, we are the first to report
      on the successful establishment and characterization of two divergent permanent
      cell lines, ie, chrompho-A and chrompho-B, derived from the same chromophobe
      renal cell carcinoma. With immunocytochemistry, two-dimensional gel
      electrophoresis, and Western blot, chrompho-A and chrompho-B exclusively
      exhibited cytokeratins (Nos. 7, 8, 18, and 19) but not vimentin. Ultrastructural
      studies revealed numerous cytoplasmic microvesicles as well as coated vesicles
      that are known to be characteristic features of the intercalated cell. Chrompho-B
      cells exhibited a shorter mean population doubling time (tD = 43 hours) than
      chrompho-A cells (tD = 51 hours). Both cell lines failed to produce tumors in
      nude mice with the subrenal capsule assay. Cytogenetic analyses revealed
      hyperdiploid chromosome numbers in both cell lines with telomeric associations as
      well as numeric aberrations known from chromophobe renal cell carcinomas in vivo.

PMID- 7717464
TI  - Expression of the histamine H1 receptor gene in relation to atherosclerosis.
AB  - Histamine in serum and arterial tissue contributes to the pathogenesis of
      atherosclerosis and the formation of coronary artery vasospasm. As the effect of
      histamine at a given site will be mediated by its specific receptors, we
      investigated by in situ hybridization and Northern blot analysis the expression
      and localization of human histamine H1 receptor mRNA in the arterial wall and in
      cultured human aortic intimal smooth muscle cells (SMC) and immortalized SMC
      (ISS10) and endothelial cells (SE1). In situ hybridization showed that SMC and
      endothelial cells expressed H1 receptor mRNA in vivo and that the expression was
      increased in SMC in the thickened intima of atherosclerotic foci in both the
      aorta and coronary artery. By Northern blot analysis, we also detected histamine
      H1 receptor mRNA in cultured SMC, ISS10, and SE1 and found that platelet-derived
      growth factor stimulated SMC to increase their expression of the mRNA in vitro.
      These results suggest that up-regulation of histamine H1 receptor expression by
      platelet-derived growth factor plays an important role in the initiation and
      progression of cardiovascular diseases.

PMID- 7717466
TI  - Pharmacological agents with effects on voice.
AB  - Pharmacological agents with the most notable effects on voice exert their
      influences on the vocal tract through the autonomic nervous system. These agents
      do not have a profound effect on laryngeal function. Their effects are subtle,
      but they are important in certain groups of patients, such as professional voice
      users. It is essential to take a thorough history of medications being used, both
      by prescription and nonprescription, when evaluating patients with voice
      disorders. It is also important to keep in mind that idiosyncratic variations may
      occur in response to medications, and careful monitoring is essential when
      patients with voice disorders are under treatment. The importance of adequate
      water intake should be emphasized for general hydration and for vocal tract
      lubrication. Understanding the autonomic nervous system and how it is influenced
      by pharmacological agents makes evaluating the effect of medicines on the vocal
      tract simpler.

PMID- 7717467
TI  - Contemporary techniques of mandibular reconstruction.

PMID- 7717465
TI  - Different subsets of T cells in conjunction with natural killer cells,
      macrophages, and activated microglia participate in the intracerebral immune
      response to Toxoplasma gondii in athymic nude and immunocompetent rats.
AB  - Oral infection of athymic nude and immunocompetent Lewis rats with Toxoplasma
      gondii induced a chronic nonlethal encephalitis. The histopathological pattern of
      Toxoplasma encephalitis was significantly different in both groups of animals and
      there were substantially larger numbers of Toxoplasma cysts in the brains of
      athymic rats. Combined immunohistochemical and flow cytometric analyses of
      intracerebral leukocytes identified alpha beta TCR+ CD4+ and CD8+ T cells;
      macrophages, and natural killer cells as inflammatory cell populations in
      immunocompetent rats, whereas in athymic rats natural killer cells, macrophages,
      and gamma delta TCR+ CD8+ CD3+ T cells contributed to the intracerebral
      inflammatory infiltrates. These findings not only point to a major participation
      of alpha beta TCR+ T cells to the intracerebral immune response, but also
      indicate that they are not essential to prevent the development of a lethal
      Toxoplasma encephalitis. In addition, microglia were strongly activated in both
      strains with simultaneous up-regulation of major histocompatibility complex class
      I and II antigens and CD4. Activation of microglia was most prominent in athymic
      rats, demonstrating that immunodeficiency does not preclude an up-regulation of
      these molecules including the human immunodeficiency virus receptor CD4 on
      microglial cells.

PMID- 7717468
TI  - Endoscopic laser management of supraglottic cancer.
AB  - Current concepts of endoscopic management of supraglottic cancer are an extension
      of precepts fostered by Jackson. The current approach has been facilitated by a
      half century of technological developments: the surgical microscope, the CO2
      laser, improved laryngoscopes, and general endotracheal anesthesia. Selected
      small-volume cancers can be curatively resected, whereas excisional biopsy can be
      performed on larger neoplasms. With this cost effective minimally-invasive
      surgical approach, there is less disturbance of normal tissue, thereby minimizing
      morbidity rate and hospitalization. If the transoral excision is inadequate,
      radiotherapy can not be depended on to eradicate known residual disease.
      Endoscopic resection of supraglottic cancer should not alter the surgeon's
      standard management of the neck.

PMID- 7717469
TI  - Maxillary sinusitis in the surgical intensive care unit: a study using bedside
      sinus ultrasound.
AB  - PURPOSE: This study investigates the incidence of acute maxillary sinusitis (AMS)
      in the surgical intensive care unit (SICU). METHODS: One hundred consecutive
      patients admitted to the SICU were examined in a prospective observational mode.
      Bedside sinus ultrasound (SUS) was performed on admission and every 48 hours.
      Patients with sinus fluid by SUS and unexplained sepsis underwent confirmatory
      sinus aspiration. RESULTS: The development of fluid in the maxillary sinus was
      identified in 15 patients by SUS. Acute maxillary sinus occurred in only 1 (1%).
      CONCLUSION: This study shows SUS to be a simple, efficient method for determining
      the presence of maxillary sinus fluid in the SICU. Acute maxillary sinus was an
      unusual finding. Our policy of avoidance of nasal instrumentation may have
      contributed to the low incidence of AMS in this high-risk patient population.

PMID- 7717470
TI  - Management of tonsillectomy hemorrhage: results of a survey of pediatric
      otolaryngology fellowship programs.
AB  - PURPOSE: To reach a consensus on the preoperative evaluation and management of
      intraoperative and postoperative tonsillectomy hemorrhage. METHOD: A survey on
      the preoperative evaluation and the management of intraoperative and
      postoperative tonsillectomy hemorrhage was given to one of the faculty members at
      each of the pediatric otolaryngology fellowship programs in the United States.
      RESULTS AND CONCLUSIONS: Seventeen surveys were distributed with 100% response.
      The majority obtained preoperative laboratory evaluation. Nearly an equal number
      of respondents preferred either cold or electrocautery dissection techniques, but
      the majority used electrocautery to control hemorrhage. After a postoperative
      bleeding episode, the results are as follows. (1) The majority favor admission
      for observation. (2) Little difference exits in the management of immediate and
      delayed hemorrhage. (3) When clot exists in the tonsillar fossae, removal is
      recommended. (4) Approximately two thirds of respondents attempt control of
      active bleeding in the emergency room, whereas the remaining proceed directly to
      the operating room. (5) After multiple episodes, a full hematologic evaluation is
      warranted. (6) Age and cooperativeness of the child is an important determinant
      in the decision-making process.

PMID- 7717471
TI  - Normal and metastatic melanin in the temporal bone.
AB  - PURPOSE: Malignant melanoma is known to metastasize to the temporal bone.
      However, melanocytes exist in the normal inner ear and may be difficult to
      distinguish from metastatic melanotic cells. This study describes distribution of
      normal melanin in the ear and metastatic melanoma to the temporal bone. MATERIALS
      AND METHODS: Normal melanin distribution is described in 48 temporal bones from
      White (18), Native-American (19), and African-American (11) individuals and
      metastatic melanoma to the temporal bone is described in four cases (seven
      temporal bones). Temporal bones were removed at autopsy, fixed in 10% buffered
      formalin, and processed for routine celloidin embedding. Sections were cut at a
      thickness of 20 microns and every tenth section was stained with hematoxylin
      eosin for light microscopic evaluation. RESULTS: Normal melanin was found in the
      inner ear, mainly around terminal neural structures and blood vessels, and
      occurred in greater quantities in African-American individuals. Metastatic
      melanotic cells reached the temporal bone by hematological dissemination, and by
      neural invasion from the central nervous system. No correlation was found between
      histopathological findings and clinical symptoms of patients. CONCLUSIONS:
      Metastatic melanoma to the temporal bone may be seen in the same areas as normal
      melanin. They may also be observed in bone marrow cells of the petrous bone and
      along the course of nerves of the internal auditory canal and cochlear vestibular
      labyrinth, either by following neural sheaths or blood vessels that run along the
      nerve. Metastatic disease to the temporal bone is often asymptomatic, or it may
      present with uncharacteristic symptoms that may delay diagnosis.

PMID- 7717472
TI  - Morphometry of the larynx in horizontal sections.
AB  - PURPOSE: Until recently, only few studies on laryngeal morphometry in the
      horizontal plane, which used unreliable techniques, have been reported. The
      established methods of whole-organ serial sectioning of the larynx serve the
      purpose of histological investigation very well. Because they cause major tissue
      shrinkage, these techniques are not useful for morphometry. Nevertheless, normal
      data of laryngeal horizontal anatomy are of great surgical and diagnostic
      interest. Data on endolaryngeal angles, airway lumina, and the thickness of parts
      of the laryngeal skeleton can be helpful in the planning of endolaryngeal
      surgical intervention or the transcutaneous placement of electrodes for laryngeal
      electromyography. The aim of this study was to establish a method for the
      production of whole-organ serial sections that allows for the collection of exact
      and reliable morphometrical data. MATERIALS AND METHODS: A total of 20 fresh
      human cadaver larynges were investigated in this study. Nineteen measurements on
      three different planes were obtained in each larynx. The larynges were shock
      frosted using liquid propane and nitrogen and then cut with a slicing machine.
      Measurements were obtained using a computer-aided analyzing system. RESULTS: The
      collected data give an exact and extensive description of the morphometrics of
      laryngeal structures such as thyroid and cricoid cartilage, arytenoid cartilages,
      vocal cords, and endolaryngeal airways at different section levels. CONCLUSION:
      This study is the first to provide detailed anthropometric data on whole-organ
      sections of the larynx following a new method. This technique of using serial
      sections of the investigated specimen avoids artifacts caused by tissue fixation.
      Thus, it may be considered being particularly suited to the conduction of
      anthropometric studies on human larynges.

PMID- 7717473
TI  - Recurrent laryngeal nerve afferents and their role in laryngospasm.

PMID- 7717474
TI  - Upper airway obstruction caused by group G streptococcal laryngitis.

PMID- 7717475
TI  - Bone regeneration within a human segmental mandible defect: a preliminary report.

PMID- 7717476
TI  - Ameloblastoma of the mandible with cervical lymph node metastasis.

PMID- 7717477
TI  - Complications of 5-fluorouracil therapy in head and neck cancer patients.

PMID- 7717479
TI  - Unlicensed drug administration.

PMID- 7717478
TI  - Costal osteomyelitis after pectoralis major myocutaneous flap use in head and
      neck reconstruction.
AB  - Costal osteomyelitis and chondritis are rare complications of PMMF usage. They
      probably represent a secondary complication of a donor-site infection. This
      diagnosis must be considered in cases of PMMF donor-site infections, which fail
      to resolve with local wound care and antibiotics. Antibiotic coverage in these
      cases should be taylored to culture results, while having broad gram-positive
      activity. Workup of these patients should include CT and biopsy to rule out a
      neoplastic process.

PMID- 7717480
TI  - The effect of midazolam premedication on implicit memory activation during
      alfentanil-nitrous oxide anaesthesia.
AB  - Eighty-three patients were given midazolam 0.1 mg.kg-1 by intramuscular injection
      as premedication before general anaesthesia with alfentanil-nitrous oxide. During
      anaesthesia patients were presented (through headphones) with either statements
      about common facts of some years ago (group A) (n = 43) or new verbal
      associations, e.g. names of fictitious, nonfamous people (group B) (n = 40). In a
      previous study with the same anaesthetic technique, but without premedication
      there was significant activation of implicit memory (p < 0.001). In this study we
      found no explicit or implicit memory for the auditory information presented
      during anaesthesia. Midazolam premedication can prevent implicit memory
      activation during alfentanil-nitrous oxide anaesthesia.

PMID- 7717481
TI  - An assessment of the consistency of ASA physical status classification
      allocation.
AB  - The American Society of Anesthesiologists' (ASA) Physical Status Classification
      was tested for consistency of use by anaesthetists. A postal questionnaire was
      sent to 113 anaesthetists of varying experience working in the Northern Region of
      England. They were asked to allot ASA grades to 10 hypothetical patients. Ninety
      seven (85.8%) responded to two mailings. In no case was there complete agreement
      on ASA grade, and in only one case were responses restricted to two of the five
      possible grades. In one case there was a significant difference in answers
      between anaesthetists with the FRCA (or equivalent) qualification, and those
      without. So much variation was observed between individual anaesthetist's
      assessments when describing common clinical problems that the ASA grade alone
      cannot be considered to satisfactorily describe the physical status of a patient.

PMID- 7717482
TI  - Determination of the reliability of three scoring systems to evaluate children
      after general anesthesia.
AB  - The inter-observer reliabilities of three scoring systems (Excitement Score, Face
      Mask Acceptance Score, Steward Score) were assessed by pairs of independent
      evaluators who observed 21 children during emergence from general anaesthesia.
      Each scoring system was analysed using the intraclass correlation coefficient
      giving values of 0.997 and 0.988 for the Excitement and Face Mask Acceptance
      Scores, respectively. Those for the Steward Score were 0.956, 0.924 and 0.295 for
      the 'consciousness', 'airway', and 'movement' subdivisions, respectively.
      Ambiguous wording and inexplicit instructions may explain the lower correlations
      for the Steward Score. Reliability of scoring systems cannot be assumed and
      systems of undocumented reliability bring into question the results of the
      studies in which they are employed.

PMID- 7717483
TI  - Magnesium deficiency in critically ill patients.
AB  - A study was performed to assess the value of estimation of intracellular
      magnesium in peripheral blood cells (red and mononuclear blood cells) in
      critically ill patients as an index of tissue magnesium content. A magnesium
      loading test was used to diagnose magnesium depletion in 16 critically ill
      patients. Patients were divided into magnesium depleted and non-depleted groups
      according to their response to the loading test. Pre-infusion plasma and
      intracellular (blood cell) magnesium levels were measured. There were no
      significant difference between the magnesium depleted (mean plasma magnesium 0.81
      mmol.l-1, red blood cell magnesium 2.34 mmol.l-1, mononuclear blood cell
      magnesium 25.16 mmol.kg-1 dry weight) and non-depleted groups (mean plasma
      magnesium 0.90 mmol.l-1, red blood cell magnesium 2.18 mmol.l-1, mononuclear
      blood cell magnesium 18.1 mmol.kg-1 dry weight). We conclude that the diagnosis
      of magnesium depletion cannot be excluded in the face of normal plasma, red blood
      cell or mononuclear blood cell concentrations of magnesium.

PMID- 7717484
TI  - Lower limb nerve blocks in children using unsheathed needles and a nerve
      stimulator.
AB  - The use of unsheathed non-insulated needles and a nerve stimulator as an aid to
      peripheral nerve blockade in children has received little attention in the
      literature. In order to assess the value of such a technique, a study was
      performed in children presenting for lower limb surgery with no contraindication
      to femoral and/or sciatic nerve block. Four hundred and eleven children, mean age
      4.25 (SD 3.8) years and mean weight 16.8 (SD 9.4) kg, received a total of 883
      peripheral nerve blocks: 419 femoral nerve blocks and 464 sciatic nerve blocks.
      One hundred and twenty six children were below one year of age. The current
      required to stimulate the more superficial femoral nerve ranged from 0.5-1.0 mA
      whilst for the deeper sciatic nerve ranged from 1.2-2.0 mA. Staff in training,
      with little or no experience of the technique, successfully performed 223 nerve
      blocks in 114 patients under the author's guidance. The overall success rate was
      98%, the failures occurring early in the series.

PMID- 7717485
TI  - Lignocaine test dose to detect intravenous injection.
AB  - The accidental intravascular injection of bupivacaine or etidocaine epidurally
      has resulted in several maternal deaths. To be effective, a test dose must allow
      detection of intravenous catheter placement and prevent accidental intravenous
      injection. This study was designed to determine the dose of lignocaine required
      for this purpose. Sixty healthy gynaecological patients were allocated randomly
      to receive an intravenous dose of normal saline (group 1), lignocaine 0.5 mg.kg-1
      (group 2) or 1 mg.kg-1 (group 3) 3 min prior to induction of anaesthesia. At 1
      min intervals the patients were asked about subjective symptoms produced by this
      'test dose'. In group 2 only 50% of patients reported a positive test dose,
      whereas in the patients of group 3, a significantly greater percentage (95%) had
      a positive test dose (p < 0.01). This suggests that the use of 1 mg.kg-1
      lignocaine as a test dose would result in a significantly higher sensitivity for
      detecting intravascular injection than the use of 0.5 mg.kg-1.

PMID- 7717487
TI  - Sedation with intravenous infusions of propofol or thiopentone. Effects on pain
      perception.
AB  - The aim of this study was to investigate pain perception during thiopentone or
      propofol infusions for sedation. Thirty ASA 1 or 2 patients received a two step
      infusion of either thiopentone (step 1: 1.25 mg.kg-1 followed by 2.5 mg.kg-1.h-1;
      step 2: 1.25 mg.kg-1 and 12.5 mg.kg-1.h-1; n = 15) or propofol (step 1: 0.5 mg.kg
      1, 1 mg.kg-1.h-1; step 2: 0.5 mg.kg-1, 5 mg.kg-1.h-1; n = 15) for sedation. At
      control and 10 min after the start of each infusion dosage, reaction times and
      thermal pain detection thresholds were determined. We found no clinically or
      statistically significant depression of thermal pain detection thresholds during
      propofol or thiopentone infusions and these are, therefore, unlikely to be
      associated with clinically relevant hyperalgesia.

PMID- 7717486
TI  - The effects of pethidine, fentanyl and lignocaine on postanaesthetic shivering.
AB  - Pethidine is reported to be more effective than equi-analgesic doses of other
      opioids as an inhibitor of postanaesthetic shivering. The aim of this study was
      to verify whether this action resulted from a local anaesthetic effect of
      pethidine or from inadequate fentanyl dosage in previous studies. We studied 52
      ASA 1 or 2 patients. They were randomly allocated, in a double-blind fashion, to
      one of four groups to receive either pethidine (0.85 mg.kg-1) or fentanyl (1.7
      micrograms.kg-1) or lignocaine (1 mg.kg-1) or 0.9% saline. All the patients were
      shivering and had a core temperature below 36 degrees C during recovery from non
      septic abdominal or orthopaedic surgery. After 15 min, all the patients given
      saline were still shivering, as were 92% in the lignocaine group. In contrast,
      only 23% of the patients who were given fentanyl still shivered (p < 0.01 versus
      saline) and 8% in the pethidine group (p < 0.001 versus saline). The mean (SD)
      core temperature in the pethidine group was slightly lower than that in the
      fentanyl group (35.1 (0.6) and 35.9 (0.5)) when the patients stopped shivering.
      Furthermore, shivering restarted in 6/10 patients in the fentanyl group after 15
      min compared with 1/12 in the pethidine group. Our results show that fentanyl
      (1.7 micrograms.kg-1) can inhibit postanaesthetic shivering but this effect is
      less pronounced and of shorter duration than with pethidine (0.85 mg.kg-1).

PMID- 7717488
TI  - Effects of ketamine on cerebral blood flow velocity in humans. Influence of
      pretreatment with midazolam or esmolol.
AB  - During normoventilation and 'light', haemodynamically stable, steady-state
      anaesthesia with isoflurane 0.3%, the effect of ketamine intravenously was
      investigated in 24 patients randomly assigned to one of the following groups:
      group 1 (control group) no ketamine, group 2 (ketamine group) ketamine 2 mg.kg-1,
      group 3 (ketamine/midazolam group) ketamine 2 mg.kg-1 after pretreatment with
      midazolam and group 4 (ketamine/esmolol group) ketamine 2 mg.kg-1 while
      maintaining mean arterial blood pressure at a preketamine level with esmolol.
      Ketamine-induced cerebrovascular changes were measured by means of transcranial
      Doppler ultrasonography. Control readings in patients without ketamine challenge
      demonstrated stable cardiovascular and cerebrovascular baseline conditions.
      Cerebral blood flow velocity and mean arterial blood pressure, however,
      significantly increased after administration of ketamine without pretreatment.
      The increase in cerebral blood flow velocity could not be blocked by maintaining
      mean arterial blood pressure at baseline value with esmolol. In contrast, the
      effects of ketamine on cerebral blood flow velocity and mean arterial blood
      pressure were prevented by prior administration of midazolam. The results suggest
      that ketamine may significantly influence intracerebral haemodynamics via a
      direct drug effect rather than via a secondary effect due to changes in arterial
      carbon dioxide and/or mean arterial blood pressure.

PMID- 7717490
TI  - Nathan Keep--William Morton's Salieri?
AB  - Dr Nathan Cooley Keep (1800-1875) was a Boston dentist and doctor who carried our
      pioneering work in both dentistry and anaesthesia. He worked with William Morton
      before the first public demonstration of ether anaesthesia, formed the world's
      first anaesthetic partnership with Morton but parted company with him and later
      opposed Morton's claim to be the sole inventor of ether anaesthesia.

PMID- 7717491
TI  - An anaesthetic inhaler with automatic thermo-compensation. 1956.

PMID- 7717489
TI  - Forced-air warming maintains normothermia during orthotopic liver
      transplantation.
AB  - We evaluated the efficacy of forced-air warming to maintain normothermia during
      liver transplantation. In a prospective, clinical trial 20 patients were randomly
      assigned to routine thermal management (circulating-water mattress set at 42
      degrees C, intravenous fluid warming to 37 degrees C and passive insulation) or
      routine management with additional forced-air warming of head, chest, and arms.
      Core temperature was measured in the pulmonary artery. Morphometric and
      demographic characteristics were similar in each group, as was total administered
      fluid volume replacement. Core temperatures in each group decreased by about 0.6
      degrees C during the first 70 min of anaesthesia and then by 0.9 degree C within
      90 to 120 min in the patients given routine thermal management, but only by 0.4
      degree C in those warmed with forced-air. Subsequently, core temperatures in the
      control group increased to only 35.7, SD 0.25 degree C whereas those in the
      patients given forced-air warming increased to 36.5, SD 0.2 degree C. Despite the
      relatively high ambient temperature, patients warmed only with a circulating
      water mattress and passive insulation became hypothermic during surgery. In
      contrast, when forced-air warming was added to this routine thermal management,
      patients were normothermic at the end of surgery. Forced-air warming prevented
      intra-operative hypothermia during liver transplantation.

PMID- 7717492
TI  - Difficult tracheal extubation in a patient with an unsuspected congenital
      subglottic stenosis.
AB  - A case is described of difficulty in advancing a tracheal tube and subsequent
      difficult extubation in an asymptomatic patient. The origin of this complication
      was an unsuspected subglottic stenosis, and a subsequent experiment showed how
      the relatively large folds of the cuff of an armoured tracheal tube could become
      caught on a narrow section of airway.

PMID- 7717493
TI  - Postoperative neuroleptic malignant syndrome.
AB  - This report describes neuroleptic malignant syndrome in a previously healthy 6
      year-old child. Droperidol and metoclopramide had been given, and hyponatraemia
      may have been a precipitating factor. Treatment with dantrolene sodium combined
      with a forced alkaline diuresis resulted in a full recovery.

PMID- 7717495
TI  - Intra-operative tracheal obstruction by tumour fragments.
AB  - A patient underwent oesophageal dilatation for invasive secondary carcinoma.
      During the course of the procedure, ventilation of the patient's lungs became
      impossible due to total tracheal obstruction. A rigid bronchoscopy was performed
      and the cause was found to be fragments of tumour that had broken off and were
      behaving like a ball-valve in the trachea and right main bronchus.

PMID- 7717494
TI  - Raynaud's syndrome following intravenous induction of anaesthesia.

PMID- 7717496
TI  - Caesarean section in a patient with protein S deficiency.
AB  - Protein S is a nonenzymatic and vitamin K-dependent cofactor of activated protein
      C. Without protein S, the anticoagulant function of protein C is almost depleted
      and thrombotic events occur. We report a parturient with hereditary protein S
      deficiency in whom the risk of thromboembolism was further complicated by
      pregnancy and who required emergency Caesarean section for fetal distress.

PMID- 7717497
TI  - Transcervical endometrial resection syndrome.
AB  - During transcervical endometrial resection the uterine cavity is irrigated under
      pressure with 1.5% glycine solution. This solution may be absorbed, with
      consequent fluid and electrolyte shifts. Plasma sodium concentration was analysed
      in 21 women undergoing transcervical endometrial resection and decreased in every
      case. In five cases this decrease was > 10 mmol.l-1. Hyponatraemia is a potential
      risk with this procedure.

PMID- 7717498
TI  - The effects of 2% lignocaine gel on incidence of retching with the use of the
      laryngeal mask airway.
AB  - This randomised, single-blind study investigated the incidence of retching during
      emergence from general anaesthesia with a laryngeal mask airway in place. Eighty
      four patients, ASA grade 1 and 2, aged 15 to 60 years, were randomly divided into
      two groups. Each patient received fentanyl 1 microgram.kg-1 and propofol 2 mg.kg
      1 for induction. A laryngeal mask airway was then inserted and the patient
      breathed spontaneously on a nitrous oxide-oxygen mixture with isoflurane. Lubafax
      gel was the lubricant in the control group and 2% lignocaine gel was used in the
      test group. The patients were allowed to wake up at the end of surgery with the
      laryngeal mask airway in place while a blinded observer observed for retching.
      The age, sex, weight and duration of surgery were similar in both groups. The
      test group had a significantly lower incidence of retching on emergence from
      general anaesthesia with the laryngeal mask airway in place (p < 0.005, Chi
      squared test).

PMID- 7717499
TI  - Management of postoperative pain by newly qualified doctors.

PMID- 7717500
TI  - Application of the back-to-basics approach to teaching medical students.

PMID- 7717501
TI  - Standards for international interhospital transfer.

PMID- 7717502
TI  - Role of on-call senior registrars.

PMID- 7717503
TI  - A small child can bite through an armoured tracheal tube.

PMID- 7717504
TI  - A comparison of 25G and 27G Whitacre needles for caesarean section.

PMID- 7717505
TI  - Nitric oxide in the pulmonary circulation during hypoxia.

PMID- 7717506
TI  - MCAD deficiency and anaesthesia.

PMID- 7717507
TI  - A facemask connector.

PMID- 7717508
TI  - A new source of gas leak from an Ohmeda Excel 410 machine.

PMID- 7717509
TI  - Incidence of gram-negative bacteraemia in sepsis syndrome.

PMID- 7717510
TI  - Premedication of children.

PMID- 7717512
TI  - Patient-controlled analgesia with alfentanil for outpatient lithotripsy.

PMID- 7717511
TI  - Scoring systems for tracheal intubation.

PMID- 7717513
TI  - Differential lung ventilation using a partial occlusion technique.

PMID- 7717514
TI  - Nasogastric tube as a tracheal tube introducer.

PMID- 7717515
TI  - Anaesthesia and public image.

PMID- 7717516
TI  - Solving a hairy problem.

PMID- 7717517
TI  - [Plethysmechanomyography (PMG). A simple method for monitoring muscle
      relaxation].
AB  - Ideal evaluation of neuromuscular blockade can be done by mechanical or
      electromyographical registration of muscle contractions evoked by ulnar nerve
      stimulation. Unfortunately, devices needed for such registration are expensive or
      complicated to set up, and thus are not often used for routine monitoring in
      anaesthesia. In this study, we describe a simple and low-priced method permitting
      intra- and postoperative monitoring of neuromuscular blocking agents. The
      accuracy of plethysmomechanomyography (PMG) was evaluated by comparing
      simultaneous electromyographic (EMG) and plethysmographic measurements. METHODS.
      For plethysmographic registration of muscle response to nerve stimulation a
      simple infusion system is twisted there to five times around one hand and
      connected to an anaesthetic monitor via a pressure transducer. The drip chamber
      is fixed about 20 cm above the hand (Fig. 1). Then, the infusion system is then
      filled up-with physiologic saline solution and the clamp is nearly closed.
      Electric stimulation can be carried out using any nerve stimulator. Using this
      method, PMG mainly records the contractions of abductor digiti minimi muscle, but
      also partly those of the interossei. Evoked muscle contractions cause stretching
      of the infusion system, which leads to pressure changes proportional to the
      strength of contraction. The muscle response to "train-of-four" (TOF) stimulation
      of the ulnar nerve was recorded simultaneously by EMG and PMG in 11 patients (ASA
      class I or II) undergoing neurosurgical procedures and therefore requiring muscle
      relaxation. After induction of anaesthesia by injection of etomidate and
      fentanyl, supramaximal stimulation and control values (T0) were defined.
      Anaesthesia was maintained by supplementation with nitrous oxide/oxygen (1:2) and
      muscle relaxation was carried out with vecuronium. We used the integrated nerve
      stimulator of a Datex Relaxograph NMT-100 EMG monitor and proceeded to stimulate
      the ulnar nerve at the forearm with supramaximal strength. The PMG was registered
      by a Siemens Siredoc 220 printer connected to a Siemens Sirecust 1281 anaesthetic
      monitor. First twitch ratio (T1/T0) and TOF ratio (T4/T1) were calculated from
      these recordings. The EMG recordings were made by a Datex Relaxograph NMT-100
      monitor, which automatically computes T1/T0 and T4/T1. The comparison of EMG and
      PMG values was carried out by simple linear regression. Statistical evaluation
      was performed using analysis of variance. RESULTS. A plethysmographically
      registered graph of the TOF-evoked muscle response is illustrated in Fig. 2.
      Simultaneous EMG and PMG recordings of onset and recovery from a nondepolarizing
      blockade are shown in Fig. 3. A strong positive correlation (P < 0.001) of EMG
      and PMG was found with correlation coefficients of 0.98 for T1/T0 and of 0.97 for
      T4/T1. The mean difference between values of both methods was 5%, maximally 18%
      (T1/T0) and 20% (T4/T1). CONCLUSIONS. Mechanomyography and EMG are well
      established methods of neuromuscular monitoring. Our data demonstrate that PMG
      provides a reliable measurement of neuromuscular transmission that correlates
      well with EMG. Since only materials of daily use in anaesthesia are needed, no
      substantial costs will arise when the plethysmographic method of measurement is
      used for routine anesthetic monitoring.

PMID- 7717518
TI  - [Axillary blockade of the brachial plexus. A prospective study of blockade
      success using electric nerve stimulation].
AB  - Axillary block is a common anesthetic technique for operations on the hand and
      forearm. In our hospital, with many trainees in anaesthesia, only 250-300
      axillary blocks per year are performed by about 30 colleagues. This implies a
      small number of blocks for each anaesthetist. The present study was designed to
      assess whether it is possible to teach this technique and use it with an adequate
      degree of success under these conditions. We used a nerve stimulator and studied
      whether the success of the block under these conditions is independent of
      anaesthetist's experience in this technique. Furthermore, we examined other
      factors involved in the success of the block. METHODS. The study included 112
      patients subjected to elective surgery of the upper extremity; all received an
      axillary block. We used a nerve stimulator and injected mepivacaine 1% without
      adrenaline. The following parameters were recorded: the number of blocks to date
      performed by the anaesthetist; the minimal current required for nerve
      stimulation; the dose of local anaesthetic; the time between the end of injection
      and the beginning of surgery; the quality of sensory and motor blockade after 10,
      20, and 30 min. Sensory blockade was assessed by the pinprick method (no
      blockade, analgesia, anaesthesia); motor blockade was judged by comparing the
      muscle strength of both arms (no blockade, paresis, paralysis). Data were
      analyzed using the Mann-Whitney test, with P < 0.05 considered statistically
      significant. RESULTS. Of the 112 blocks, 95 (85%) were successful; 17 (15%)
      failed and the patients required general anaesthesia. Eight of the successful
      blocks showed a decrease in analgesic quality after > or = 70 min and required
      additional analgesics or general anaesthesia. We found no correlation between the
      experience of the anaesthetist and the success of the block. The minimal required
      current for nerve stimulation in the success group was 0.4 mA and differed
      significantly from the value of 0.6 mA in the failure group (Table 3). The dose
      of mepivacaine was higher in the success group (5.9 vs. 5.3 mg/kg). Complete
      sensory blockade was more frequently achieved for the median, ulnar, and radial
      nerves than for the musculocutaneus and cutaneous brachii medialis (Fig. 3). The
      frequency of complete sensory blockade (anaesthesia) had increased by 21.9%
      between the 20th and 30th min. Complete motor blockade was less often achieved
      than sensory blockade (Fig. 4). CONCLUSIONS. Using the method of
      electrostimulation, the axillary block is an appropriate anaesthetic technique
      that can be applied in a hospital where each anaesthetist only occasionally
      performs it. Prior to injection of the local anaesthetic, the current for nerve
      stimulation should be reduced to < 0.5 mA. The time between the end of injection
      and the beginning of surgery should be no less than 30 min because complete
      sensory blockade can more often be achieved. The dose of mepivacaine should be no
      less than 6 mg/kg body weight.

PMID- 7717520
TI  - [Anesthesiology....].

PMID- 7717519
TI  - [Trauma and circulatory arrest. 224 preclinical resuscitations in Cologne in 1987
      1990].
AB  - Posttraumatic cardiopulmonary resuscitation (CPR) is associated with a poor
      outcome. When evaluating the literature according to the Utstein method, there
      were only 2 survivors (0.18%) out of 1,135 CPR attempts after trauma (Table 1).
      Differences in the study populations and levels of prehospital trauma care led us
      to analyse the results of a physician-staffed prehospital trauma care system in
      Cologne. METHODS. From January 1987 to December 1990, a total of 49,054 emergency
      calls were registered using a standardised protocol. Among 9,595 trauma-related
      calls, 636 patients were found to be pulseless on arrival of the emergency team,
      412 of these were pronounced dead. CPR was initiated in the remaining 224
      patients, who comprise the study population (defined as 100%). All patients who
      were admitted to a hospital were followed using a second protocol. RESULTS. CPR
      in the field was successful in 68 (30.4%) patients, who were then admitted to a
      hospital; 42 of these died within the first 24 h. Four patients (1.8%) could be
      discharged from hospital alive and were still living 1 year later, 1 with a
      lasting neurological deficit (Fig. 1). In 156 (69.6%) cases resuscitative
      attempts were unsuccessful in the field. CONCLUSIONS. Even in a physician-staffed
      prehospital trauma care system, the chance of surviving a posttraumatic cardiac
      arrest is minimal. Survival has to be regarded as an individual fate; the overall
      results are discouraging. Even though this study analyses the largest population
      of posttraumatic CPR ever published, prognostic factors could not be identified
      due to the few survivors. Nevertheless, the result does not justify general
      omission of CPR after trauma as: (1) prognostic factors for survival have not
      been identified thus far; and (2) no significant additional costs arise from
      posttraumatic CPR.

PMID- 7717521
TI  - [Stress bleeding. 1. Pathogenesis, clinical picture and therapy].
AB  - Acute upper gastrointestinal bleeding in ICU patients has many possible causes:
      ulcer, adverse drug effects, gastric tube lesion, acute renal or liver failure,
      or stress-induced gastric mucosal lesion. Stress-induced gastric mucosal lesions
      typically are multiple superficial erosions, while ulcerations typically occur in
      patients with head trauma, neurosurgical operation or severe burns. Head trauma
      and neurosurgical patients are the only ones with increases gastric acid
      secretion; in general reduced acid secretion can be observed in ICU patients. An
      active acid secreting stomach has been shown to be more resistant against mucosal
      damage than a stomach with basal activity. Active acid secretion depends on
      sufficient oxygen supply and mucosal ATP content. Hypotension and shock results
      in gastric mucosal ischaemia. These are the most important risk factors of stress
      bleeding.

PMID- 7717522
TI  - [A compilation of therapeutic and toxic plasma drug concentrations].
AB  - In order to assess the significance of drug levels measured in clinical and
      forensic toxicology as well as for therapeutic drug monitoring (TDM), it is
      essential that good collections of data are readily available. For more than 400
      frequently used drugs therapeutic and, if data were available, toxic and fatal
      plasma concentrations as well as elimination half-lives were compiled in a table
      including, e.g., hypnotics like barbiturates and benzodiazepines, neuroleptics,
      antidepressants, sedatives, analgesics, anti-inflammatory agents, antihistamines,
      anti-epileptics, beta-adrenergic antagonists, antibiotics (penicillins,
      cephalosporins, aminoglycosides, gyrase inhibitors), diuretics, calcium-channel
      blockers, cardiac glycosides, anti-arrhythmics, anti-asthmatics, angiotensin
      converting enzyme inhibitors, opioid agonists, and local anaesthetics. Data have
      been abstracted from published information, both compilations and primary
      sources, and supplemented with data collected in our own forensic and clinical
      toxicology laboratories. Wherever possible, ranges for therapeutic plasma
      concentrations are expressed as trough concentration at steady-state. The range
      of (or single) half-life values given for each drug are chosen to represent the
      terminal log-linear phase at most. In addition to the assessment of significance
      of drug levels for the therapeutic monitoring of patients, this list can assist
      the diagnostic assessment in cases of intoxication.

PMID- 7717523
TI  - Determination of catecholamines in single adrenal medullary cells by capillary
      electrophoresis and laser-induced native fluorescence.
AB  - The present study demonstrates that native fluorescence detection combined with
      capillary electrophoresis separation at low pH provides high sensitivity (down to
      nanomolar), high resolution, high speed, and low interference for the analysis of
      catecholamines. Further, this method has been employed successfully for the
      measurement of the amounts of epinephrine and norepinephrine in individual bovine
      adrenal medullary cells. Application of this method to the study of
      neurochemistry is promising.

PMID- 7717524
TI  - Optimal coating selection for the analysis of organic vapor mixtures with polymer
      coated surface acoustic wave sensor arrays.
AB  - A method for determining the optimal set of polymer sensor coatings to include in
      a surface acoustic wave (SAW) sensor array for the analysis of organic vapors is
      described. The method combines an extended disjoint principal components
      regression (EDPCR) pattern recognition analysis with Monte Carlo simulations of
      sensor responses to rank the various possible coating selections and to estimate
      the ability of the sensor array to identify any set of vapor analytes. A data
      base consisting of the calibrated responses of 10 polymer-coated SAW sensors to
      each of six organic solvent vapors from three chemical classes was generated to
      demonstrate the method. Responses to the individual vapors were linear over the
      concentration ranges examined, and coatings were stable over several months of
      operation. Responses to binary mixtures were additive functions of the individual
      component responses, even for vapors capable of strong hydrogen bonding. The
      EDPCR-Monte Carlo method was used to select the four-sensor array that provided
      the least error in identifying the six vapors, whether present individually or in
      binary mixtures. The predicted rate of vapor identification (87%) was
      experimentally verified, and the vapor concentrations were estimated within 10%
      of experimental values in most cases. The majority of errors in identification
      occurred when an individual vapor could not be differentiated from a mixture of
      the same vapor with a much lower concentration of a second component. The
      selection of optimal coating sets for several ternary vapor mixtures is also
      examined. Results demonstrate the capabilities of polymer-coated SAW sensor
      arrays for analyzing of solvent vapor mixtures and the advantages of the EDPCR
      Monte Carlo method for predicting and optimizing performance.

PMID- 7717526
TI  - DNA conformational dynamics in polymer solutions above and below the entanglement
      limit.
AB  - Video microscopy of nucleic acids (DNA) undergoing electrophoresis in
      hydroxyethyl cellulose (HEC) sieving buffers demonstrates previously unobserved
      shape-changing interactions between DNA and HEC molecules. We provide the first
      visual demonstration of entanglement between DNA and one or several discrete HEC
      molecules, which has been postulated to occur in ultradilute polymer solutions.
      Typically, nucleic acids appear to become entangled with HEC at a single region
      only, in both dilute and fully entangled HEC solutions. Fluctuations of the
      center of mass velocity of a DNA molecule and its correlation with conformation
      are revealed from analyses of the image data. These observations account for the
      success of recently reported rapid, high-resolution dc and pulsed-field capillary
      electrophoretic separations of nucleic acids in ultradilute hydroxyethyl
      cellulose solutions and hydroxyethyl cellulose/poly(ethylene oxide) solutions.

PMID- 7717525
TI  - Fast-scan cyclic voltammetry of 5-hydroxytryptamine.
AB  - Fast-scan cyclic voltammetry, a demonstrated analytical method for the in vivo
      detection of dopamine, is extended to the detection of in vitro and in vivo 5
      hydroxytryptamine (5-HT) with the use of a specific potential wave form applied
      at 1000 V/s. The wave form, 0.2 to 1.0 to -0.1 to 0.2 V, is employed to
      accelerate electrode response times which are significantly slower with other
      wave forms due to the adsorption of 5-HT. The scan rate of 1000 V/s enables
      follow-up reactions which lead to the formation of strongly adsorptive products
      to be outrun. The peak current at a carbon fiber disk microelectrode exposed to 1
      microM 5-HT in flow injection experiments is 1 nA, with a half-rise time of less
      than 200 ms. The peak current of Nafion-coated electrodes exposed to the same
      concentration of 5-HT is 5 nA, with a half-rise time on the order of 400 ms. The
      rate of adsorption of 5-HT was determined to be 4.22 +/- 0.33 s-1. Several
      compounds present in brain tissue as well as the pharmacological agents used to
      elicit 5-HT release in the caudate of the rat were evaluated. Those which gave a
      response could be differentiated from 5-HT on the basis of respective oxidative
      and reductive peak potentials. Nafion-coated electrodes were used to monitor
      transient increases in both dopamine and exogenous 5-HT in the caudate of the
      anesthetized rat in response to electrical stimulation. The rate of cellular
      uptake of 5-HT was shown to be 3-fold slower than dopamine uptake. NS-15841

PMID- 7717527
TI  - Near-infrared measurement of relative and absolute humidity through detection of
      water adsorbed on a silica gel layer.
AB  - Near-IR spectroscopy is especially well suited to moisture determination because
      of the relatively high absorptivity of water compared to most other substances.
      In the present work, near-IR diffuse-transmittance spectroscopy is applied to the
      measurement of humidity via observation of adsorbed water on a high-performance
      thin-layer chromatography silica gel plate. The adsorbed water is detected
      through both ordinary absorption of radiation by water molecules and the
      increased scattering of near-IR radiation by the silica gel as it adsorbs more
      water. This technique shows promise as a highly accurate and sensitive humidity
      sensor with a time constant of less than 1 min. The addition of inorganic salts
      to the silica gel layer is shown to increase the response to water vapor.
      However, it also increases the time constant of the sensor. A miniature humidity
      sensor using a commercially available near-IR transmissive switch is also
      demonstrated. Possible interferences and hysteresis effects are investigated.

PMID- 7717529
TI  - Multifaceted alterations of the thalamo-cortico-thalamic loop in adult rats
      prenatally exposed to ethanol.
AB  - The thalamo-cortico-thalamic loop was investigated in adult rats exposed to
      ethanol during the last week of fetal life. Animals underwent either cortical or
      thalamic injections of lectin-conjugated horseradish peroxidase. Results
      demonstrate that prenatal exposure to ethanol causes permanent changes in the
      thalamocortical circuits. Alterations of thalamo-cortical and cortico-thalamic
      projections are concentrated at the level of axon terminal fields. The most
      severe thalamic damage is observed in the anterior intralaminar and midline
      nuclei; crossed cortico-thalamic projections also appear to be severely impaired.
      In the cortex, the damage to thalamic terminals displays a medio-lateral gradient
      of increasing severity through sensori-motor areas, with the lateral fields more
      impaired. Cells of origin of thalamo-cortical and cortico-thalamic projections
      are less affected by prenatal ethanol exposure: in the thalamus and layer 5 of
      sensori-motor cortex labeled cells exhibit normal values of areal numeric
      density. Conversely, cortico-thalamic neurons of layer 6, especially in the
      lateral agranular sensori-motor field, display smaller values of areal density
      than those of normal animals. Possible mechanisms underlying the establishment of
      these abnormalities are discussed.

PMID- 7717530
TI  - Morphology of vomeronasal organ cultures from fetal rat.
AB  - The vomeronasal organs (VNOs) of rats were cultured from embryonic 15-day
      littermates on collagen-coated membrane in Dulbecco's modified Eagle's medium
      containing serum. The explants were observed sequentially and fixed at 4, 6, 8,
      10 and 14 days in vitro (DIV). Organogenesis of VNOs and cell differentiation
      took place in vitro. Patterns of organogenesis of the VNO in vitro were different
      from those in vivo. Both sensory and supporting cells in the sensory epithelium
      had microvilli on their surface. Epithelial cells in aggregates of non-sensory
      epithelial cells had cilia and microvilli on their surface. Vomeronasal axons
      forming two to three large fascicles were seen originating from the VNO at 4, 6,
      and 8 DIV, and degenerated at 10 or 14 DIV. Glial cells (ensheathing cells) were
      observed in the fascicles. These morphological characteristics of VNO cells in
      vitro were similar to those observed in vivo.

PMID- 7717528
TI  - Potential roles for tumour necrosis factor alpha during embryonic development.
AB  - This paper reviews the evidence indicating possible roles for tumour necrosis
      factor-alpha (TNF alpha) in development. It is proposed that TNF alpha may have
      essentially three major roles during embryonic development, which may be
      analogous to its roles in the immune system and during inflammation: a role in
      programmed cell death; a role as a cellular growth and differentiation factor;
      and also a role in the remodelling of extracellular matrix, and the regulation of
      cell adhesion molecules and integrins. The concept of the existence of a cytokine
      array during embryogenesis, analogous to that occurring in inflammation, is
      discussed, as well as potential roles for TNF alpha in the induction of
      ubiquitin; protective mechanisms embryonic cells may employ against TNF alpha
      mediated cytotoxicity; and a consideration of the role TNF alpha may play in a
      "free radical theory of development".

PMID- 7717531
TI  - Immunohistochemical localization of laminin and type IV collagen in human
      cutaneous sensory nerve formations.
AB  - We used immunohistochemical techniques and monoclonal antibodies to localize two
      basement membrane components (laminin and type IV collagen) in the nerves and
      sensory nerve formations, or corpuscles, supplying human digital skin.
      Furthermore, neurofilament proteins, S-100 protein and epithelial membrane
      antigen were studied in parallel. In dermal nerve trunks, immunostaining for
      laminin and type IV collagen was found to be co-localized in the perineurium and
      the Schwann cells, the stronger immunoreactivity being at the external surface of
      the cells. In the Meissner digital corpuscles, the immunoreactivity for laminin
      and type IV collagen was mainly observed underlying the cell surface of lamellar
      cells, while the cytoplasm was weakly immunolabelled or unlabelled. Finally,
      within Pacinian corpuscles co-localization of the two basement membrane molecules
      was encountered in the inner core, intermediate layer, outer core and capsule.
      Laminin and type IV collagen immunoreactivities were also found in blood vessels
      and sweat glands, apparently labelling basement membrane structures. The present
      results provide evidence for the presence of basement membrane in all periaxonic
      cells forming human cutaneous sensory nerve formations, and suggest that all of
      them are able to synthesize and release some basement membrane components, such
      as laminin and type IV collagen. The possible role of laminin in sensory nerve
      formations is discussed.

PMID- 7717532
TI  - Immunocytochemical characterization of porcine zona pellucida during follicular
      development.
AB  - Sections of bovine ovaries fixed in Bouin's fluid or methanol-acetic acid and
      embedded in paraffin were incubated with chicken polyclonal antibodies to HPLC
      purified zona glycoproteins ZP3 alpha and ZP3 beta. Oocytes of primordial
      follicles as well as of primary follicles showed weak labelling with anti-ZP3
      alpha and anti-ZP3 beta. No immunostaining could be observed in the follicle
      cells. The ZP of primary follicles displayed distinct immunoreactivity for both
      ZP3 alpha and ZP3 beta. In secondary follicles, distinct labelling with anti-ZP3
      beta and weak labelling with anti-ZP3 alpha could be seen in the oocyte. The ZP
      showed immunoreactivity with antibodies to ZP3 alpha and ZP3 beta. Both
      antibodies labelled single follicle cells. In tertiary follicles, the oocytes
      were weakly labelled with anti-ZP3 alpha and anti-ZP3 beta. Some granulosa cells
      showed staining for ZP3 alpha and ZP3 beta. The ZP displayed strong
      immunoreactivity for ZP3 beta and ZP3 alpha. Cells of the corona radiata were
      strongly immunopositive for ZP3 alpha and ZP3 beta. Similar histotopography of
      immunoreactive cells could be seen in preovulatory follicles. The characteristic
      pattern observed for the distribution of ZP3 alpha and ZP3 beta strongly suggests
      that in the porcine ovary both the oocyte and the follicle cells contribute to
      the synthesis of the ZP, perhaps in sequence.

PMID- 7717534
TI  - The role of extracardiac factors in normal and abnormal development of the chick
      embryo heart: cranial flexure and ventral thoracic wall.
AB  - The present study was designed to investigate whether the formation of the
      cranial flexure is involved in the normal positional changes of the embryonic
      heart tube that occur during its transformation from the c- to s-shaped loop. For
      this purpose, the formation of the cranial flexure was locally suppressed in
      chick embryos by introducing a straight hair into the neural canal. In the
      experimental embryos, prevention of cranial flexure did not suppress the normal
      positional changes of the heart tube. However, other anomalies in the looping of
      the heart tube were frequently observed. These anomalies were caused by
      alterations in the formation of the ventral thoracic wall, which in turn seemed
      to be related not to the prevention of the cranial flexure but rather to
      accidental injuries during the implantation of the hair. In the embryos with
      abnormal looping of the heart tube, the incidence of delayed/defective septation
      of the heart was significantly higher than in embryos with normal looping. These
      results show that in the chick embryo: (1) cranial flexure is not involved in
      normal positional changes of the heart loop; (2) manipulations at the head region
      of the embryo can unintentionally result in developmental disorders of the
      ventral thoracic wall; (3) such disorders can result in congenital heart defects
      through mechanical interference with normal looping of the embryonic heart. The
      possible significance of these findings for the evaluation of experimental
      studies of chick embryos is discussed in the context of anomalies observed after
      surgical ablation of the premigratory cranial neural crest.

PMID- 7717533
TI  - Characterization of glycoconjugate expression during development of Meckel's
      cartilage in the rat.
AB  - The staining patterns of 24 biotinylated lectins were analyzed in serial sections
      of the mandible of 13- to 21-day-old rat embryos by means of the avidin-biotin
      peroxidase method. A ubiquitous distribution of binding sites was demonstrated
      after incubation with Con A (Canavalia ensiformis), DSL (Datura stramonium;
      except bone matrix), and WGA (Triticum vulgare). ECL (Erythrina cristagalli), GSL
      I (Griffonia simplicifolia), SJA (Saphora japonica), VVL (Vicia villosa), DBA
      (Dolichus biflorus), UEA I (Ulex europeus), and LTA (Lotus tetragonobolus) were
      constantly negative. In early stages of development, GSL II (Griffonia
      simplicifolia II) was a selective marker of prechondral blastema. In contrast,
      PNA (Arachis hypogaea) did not stain condensing mesenchyme. During chondrogenesis
      of Meckels's cartilage a general decrease of lectin binding was observed. Mature
      cartilage matrix was constantly negative. Chondrocytes were marked by the lectins
      PSA (Pisum sativum), WGA, PHA-E, and PHA-L (Phaseolus vulgaris E and L). A strong
      GSL II binding was restricted to the mesial-superior region of the perichondrium.
      In later stages, several lectins revealed significant differences between
      preskeletal ("central") areas and the remaining ("peripheral") mesenchyme. A
      clear binding reaction was noted in central regions by applying LEA (Lycopersicon
      esculentum) and STL (Solanum tuberosum), while the peripheral tissue was only
      faintly stained. Developing bone was specifically marked by succinylated WGA
      (sWGA). The lectins LCA (Lens culinaris) and RCA (Ricinus communis) bound to
      fibers and extracellular matrix of the connective tissue. Jacalin (Artocarpus
      integrifolia) and SBA (Glycine max) binding sites were found in macrophages.
      Affinity of VAA (Viscum album) increased parallel with maturation of endothelial
      cells. Specific lectin-binding patterns revealed no correlation with the
      distribution of glycosaminoglycans. The results demonstrate a general reduction
      of oligosaccharide structures during development of Meckel's cartilage. From our
      observations we conclude that intralaminar glucose and/or mannose sequences as
      well as terminal sialic acid molecules are ubiquitously distributed, while
      terminal alpha-fucose was constantly negative. Lectin-binding patterns of
      macrophages may reflect the presence of specifically linked terminal galactose.
      Our findings indicate that oligosaccharides terminating in N-acetylglucosamine
      are bone-specific. The significance of the restricted staining of the
      perichondrium by GSL II remains to be elucidated.

PMID- 7717535
TI  - Triiodothyronine increases contractility independent of beta-adrenergic receptors
      or stimulation of cyclic-3',5'-adenosine monophosphate.
AB  - BACKGROUND: Triiodothyronine regulates cardiac contractility; however, the
      mechanisms by which it produces its acute contractile effects remains unknown. We
      compared the acute effects of thyroid hormones (triiodothyronine [T3] and
      thyroxine [T4]) and of isoproterenol on the contractility of isolated rat hearts.
      In addition, we sought to determine whether the acute inotropic effects of
      thyroid hormones were mediated by beta-adrenergic receptors or by increased
      production of cyclic-3',5'-adenosine monophosphate (cAMP). METHODS: A Langendorff
      heart preparation harvested from euthyroid male Sprague-Dawley rats was used.
      Drugs were administered through an aortic perfusion catheter. A pressure
      transduced left-ventricular balloon catheter measured pressure and heart rate
      changes. Changes in the maximum positive rate of change in pressure (dP/dT) and
      maximum negative dP/dT were determined. Responses to varying doses of T3, T4, and
      isoproterenol were assessed in the presence and absence of beta-adrenergic
      receptor blockade with propranolol. cAMP production, measured by
      radioimmunoassay, was determined in myocardial cell suspensions after incubation
      with T3 or isoproterenol. RESULTS: T3 0.74 nmol rapidly and significantly
      increased maximum dP/dT by 335 +/- 38 mmHg/s within 30 s after bolus injection;
      however, contractility was unchanged after as much as 12.9 nmol T4. The maximal
      increase in dP/dT after 0.8 nmol isoproterenol was comparable to that produced by
      T3. However, the cardiotonic actions of isoproterenol were significantly slower
      to develop (peaking at 60 vs. 15 s) and lasted longer than those of T3.
      Pretreatment with propranolol 1 mumol diminished the contractile effects of
      isoproterenol but had no effect on those of T3. Concentrations of isoproterenol
      that increase contractility also significantly increased cAMP production in
      isolated rat myocardial cells. However, T3 failed to increase cAMP production.
      CONCLUSIONS: These results demonstrate that the acute inotropic effects of T3 are
      not shared by T4 and appear unrelated to beta-adrenergic receptor mechanisms or
      to generation of cAMP. Thus, T3 acutely stimulates cardiac contraction by
      mechanisms that differ from those of the more commonly used beta-adrenergic
      receptor agonists and phosphodiesterase inhibitors. Further studies are needed to
      identify the mechanisms underlying the acute contractile effects of T3 and to
      determine whether T3 will prove useful for increasing ventricular function in
      patients.

PMID- 7717536
TI  - Neurologic evaluation of the rat during sciatic nerve block with lidocaine.
AB  - BACKGROUND: Quantitative behavioral testing is necessary to establish a
      reproducible measure of differential functional blockade during regional
      anesthesia. Methods for assessment of the neurologic status (mental status,
      posture, gait, proprioception, motor function, autonomic function, and
      nociception) in veterinary neurology were adapted for the rat and used to monitor
      functional changes separately during a sciatic nerve block. METHODS: Sprague
      Dawley rats were acclimated to laboratory routine before the study so that
      lidocaine (0.1 ml, 1%) could be injected near the sciatic notch without any
      chemical restraint. The onset, duration, and magnitude of functional losses were
      monitored. Proprioceptive integrity was evaluated by assessing the response to
      tactile placing and the hopping response. Extensor postural thrust, a test for
      postural reactions in small animals, was assessed on a digital balance and found
      adequate for quantifying motor function. Analgesia was assessed by measuring
      withdrawal response latencies to noxious thermal stimulation (51 degrees C) and
      to superficial and deep noxious pinches. Autonomic function was monitored by
      measuring skin temperature. Contralateral limb function was used as an internal
      control, and injection of saline was used as an external control in separate,
      control animals. RESULTS: Onset of postural and gait abnormalities were observed
      as early as 40 s after injection. On each occasion proprioceptive impairment was
      detected first, followed by impairment of motor function and nociception.
      Complete absence of proprioception occurred from 10 to 30 min (n = 9) and of
      motor function at 30 min after injection (n = 10); both functions were fully
      recovered by 120 min. A unilateral increase in skin temperature on the foot was
      detected by 1 min; had reached its maximum change, 5.3 +/- 0.7 degrees C, at 10
      min; and had returned to control levels at 60 min after injection (n = 12).
      Withdrawal response to cutaneous or superficial pain was absent in all ten
      animals from 5 to 30 min whereas the response to deep pain was absent in all ten
      animals at 20 min only. The response to noxious stimulation recovered at 90 min.
      Attention was paid to the temporal relation of the impairment of various
      functions. CONCLUSIONS: Quantitative observations of the onset, offset, and
      intensity of differential functional impairment or block over time will make it
      possible to establish the doses and conditions for local anesthetics that result
      in differential nerve block and will permit comparison of these changes among
      different drugs and "clinical" protocols.

PMID- 7717537
TI  - The pathophysiology of aortic cross-clamping and unclamping.

PMID- 7717538
TI  - Percutaneous aspiration of lumbar facet synovial cyst.

PMID- 7717539
TI  - Nasotracheal intubation in the presence of a pharyngeal flap in children and
      adults.

PMID- 7717540
TI  - Methemoglobinemia in a patient receiving flutamide.

PMID- 7717541
TI  - Anesthesia for aortic and mitral valve replacement in a patient with carcinoid
      heart disease.

PMID- 7717542
TI  - Practice guidelines for acute pain management in the perioperative setting. A
      report by the American Society of Anesthesiologists Task Force on Pain
      Management, Acute Pain Section.

PMID- 7717543
TI  - Transesophageal atrial pacing facilitates pulmonary artery catheter placement.

PMID- 7717544
TI  - A trap of our own making.

PMID- 7717545
TI  - Right, wrong, and surrogate endpoints.

PMID- 7717546
TI  - Right, wrong, and surrogate endpoints.

PMID- 7717547
TI  - Nasotracheal intubation in children.

PMID- 7717548
TI  - Thromboelastography as a guide to platelet transfusion.

PMID- 7717549
TI  - Is intraoperative roentgenography justified?

PMID- 7717550
TI  - When is the ex-premature infant no longer at risk for apnea?

PMID- 7717551
TI  - Postoperative apnea in former preterm infants after inguinal herniorrhaphy. A
      combined analysis.
AB  - BACKGROUND: Controversy exists as to the risk for postoperative apnea in former
      preterm infants. The conclusions of published studies are limited by the small
      number of patients. METHODS: The original data from eight prospective studies
      were subject to a combined analysis. Only patients having inguinal herniorrhaphy
      under general anesthesia were included; patients receiving caffeine, regional
      anesthesia, or undergoing other surgical procedures were excluded. A uniform
      definition for apnea was used for all patients. Eleven risk factors were
      examined: gestational age, postconceptual age, birth weight, history of
      respiratory distress syndrome, bronchopulmonary dysplasia, neonatal apnea,
      necrotizing enterocolitis, ongoing apnea, anemia, and use of opioids or
      nondepolarizing muscle relaxants. RESULTS: Two hundred fifty-five of 384 patients
      from eight studies at four institutions fulfilled study criteria. There was
      significant variation in apnea rates and the location of apnea (recovery room and
      postrecovery room) between institutions (P < 0.001). There was considerable
      variation in the duration and type of monitoring, definitions of apnea, and
      availability of historical information. The incidence of detected apnea was
      greater when continuous recording devices were used compared to standard
      impedance pneumography with alarms or nursing observations. Despite these
      limitations, it was determined that: (1) apnea was strongly and inversely related
      to both gestational age (P = 0.0005) and postconceptual age (P < 0.0001); (2) an
      associated risk factor was continuing apnea at home; (3) small-for-gestational
      age infants seemed to be somewhat protected from apnea compared to appropriate-
      and large-for-gestational-age infants; (4) anemia was a significant risk factor,
      particularly for patients > 43 weeks' postconceptual age; (5) a relationship to
      apnea with history of necrotizing enterocolitis, neonatal apnea, respiratory
      distress syndrome, bronchopulmonary dysplasia, or operative use of opioids and/or
      muscle relaxants could not be demonstrated. CONCLUSIONS: The analysis suggests
      that, if it is assumed that the statistical models used are equally valid over
      the full range of ages considered and that the average rate of apnea reported
      across the studies analyzed is accurate and representative of actual rates in all
      institutions, the probability of apnea in nonanemic infants free of recovery-room
      apnea is not less than 5%, with 95% statistical confidence until postconceptual
      age was 48 weeks with gestational age 35 weeks. This risk is not less than 1%,
      with 95% statistical confidence, for that same subset of infants, until
      postconceptual age was 56 weeks with gestational age 32 weeks or postconceptual
      age was 54 weeks and gestational age 35 weeks. Older infants with apnea in the
      recovery room or anemia also should be admitted and monitored. The data do not
      allow prediction with confidence up to what age this precaution should continue
      to be taken for infants with anemia. The data were insufficient to allow
      recommendations regarding how long infants should be observed in recovery. There
      is additional uncertainty in the results due to the dramatically different rates
      of detected apnea in different institutions, which appear to be related to the
      use of different monitoring devices. Given the limitations of this combined
      analysis, each physician and institution must decide what is an acceptable risk
      for postoperative apnea.

PMID- 7717552
TI  - Effects of fentanyl on sympathetic activation associated with the administration
      of desflurane.
AB  - BACKGROUND: Activation of the sympathetic nervous system occurs when desflurane
      is inspired shortly after anesthetic induction and when the inspired
      concentration of desflurane is rapidly increased during steady-state periods of
      anesthesia. The purpose of this study was to determine the effectiveness and dose
      response of fentanyl pretreatment in attenuating the neurocirculatory responses
      to desflurane in healthy human volunteers. METHODS: After Institutional Research
      Review Board approval, three study groups were selected and, in random order,
      received either placebo (n = 10), a 2.5-micrograms.kg-1 intravenous bolus of
      fentanyl citrate followed by a continuous infusion of 1 microgram.kg-1.h-1 (n =
      9), or a 5.0-micrograms.kg-1 intravenous bolus followed by an infusion of 2
      micrograms.kg-1.h-1 (n = 11) before the administration of desflurane. Arterial
      (MAP) and central venous (CVP) pressures were measured directly, and heart rate
      (HR) was determined indirectly. Efferent muscle sympathetic nerve activity (SNA)
      was recorded from the peroneal nerve by microneurography. After neurocirculatory
      recordings at conscious unmedicated baseline and 12 min after fentanyl
      administration, anesthetic induction was carried out with 2.0 mg.kg-1 propofol
      and 0.2 mg.kg-1 vecuronium. Neurocirculatory measurements were repeated beginning
      2 min after induction when desflurane was given via mask (semiclosed circle
      system, 61/min fresh gas flow, 100% O2) in three incremental 1-min steps (3.6%,
      7.2%, and 11%). Intubation occurred 10 min after propofol administration. Twenty
      minutes after intubation, recordings were obtained during two steady-state
      periods during which end-tidal concentrations had achieved 5.4% (0.75 MAC) and
      11% (1.5 MAC) desflurane for at least 10 min. Data also were obtained during the
      rapid increase in the inspired gas concentration from 5.4% to 11% ("transition").
      RESULTS: Neurocirculatory variables did not differ between the three groups at
      conscious baseline, after fentanyl, and during steady-state periods of
      anesthesia. Propofol administration significantly reduced SNA and MAP. The MAP
      reduction was enhanced in the fentanyl-treated groups. After induction, the
      increases in SNA and MAP associated with the administration of desflurane by mask
      were not significantly reduced by fentanyl. The transition from 5.4% to 11%
      desflurane resulted in increases in SNA, HR, MAP, and fentanyl administration
      significantly attenuated the HR and MAP components. At the 11% steady-state
      measurement period, CVP was increased and MAP was decreased from conscious
      baseline, and these changes were not modified by fentanyl. CONCLUSIONS: The
      administration of desflurane was associated with increases in SNA, HR, MAP, and
      CVP. Maximum sympathetic activation and hemodynamic responses occurred 4-5 min
      after initiating desflurane during induction and 2-3 min after increasing the
      inspired concentration of desflurane during the "transition" period. Although
      fentanyl partially attenuated the hemodynamic component in a dose-dependent
      fashion during the "transition" period, it did not significantly diminish the
      response during induction.

PMID- 7717553
TI  - Influence of gas composition on recurrence of atelectasis after a reexpansion
      maneuver during general anesthesia.
AB  - BACKGROUND: Atelectasis, an important cause of impaired gas exchange during
      general anesthesia, may be eliminated by a vital capacity maneuver. However, it
      is not clear whether such a maneuver will have a sustained effect. The aim of
      this study was to determine the impact of gas composition on reappearance of
      atelectasis and impairment of gas exchange after a vital capacity maneuver.
      METHODS: A consecutive sample of 12 adults with healthy lungs who were scheduled
      for elective surgery were studied. Thirty minutes after induction of anesthesia
      with fentanyl and propofol, the lungs were hyperinflated manually up to an airway
      pressure of 40 cmH2O. FIO2 was either kept at 0.4 (group 1, n = 6) or changed to
      1.0 (group 2, n = 6) during the recruitment maneuver. Atelectasis was assessed by
      computed tomography. The amount of dense areas was measured at end-expiration in
      a transverse plane at the base of the lungs. The ventilation-perfusion
      distributions (VA/Q) were estimated with the multiple inert gas elimination
      technique. The static compliance of the total respiratory system (Crs) was
      measured with the flow interruption technique. RESULTS: In group 1 (FIO2 = 0.4),
      the recruitment maneuver virtually eliminated atelectasis for at least 40 min,
      reduced shunt (VA/Q < 0.005), and increased at the same time the relative
      perfusion to poorly ventilated lung units (0.005 < VA/Q < 0.1; mean values are
      given). The arterial oxygen tension (PaO2) increased from 137 mmHg (18.3 kPa) to
      163 mmHg (21.7 kPa; before and 40 min after recruitment, respectively; P =
      0.028). In contrast to these findings, atelectasis recurred within 5 min after
      recruitment in group 2 (FIO2 = 1.0). Comparing the values before and 40 min after
      recruitment, all parameters of VA/Q were unchanged. In both groups, Crs increased
      from 57.1/55.0 ml.cmH2O-1 (group 1/group 2) before to 70.1/67.4 ml.cmH2O-1 after
      the recruitment maneuver. Crs showed a slow decrease thereafter (40 min after
      recruitment: 61.4/60.0 ml.cmH2O-1), with no difference between the two groups.
      CONCLUSIONS: The composition of inspiratory gas plays an important role in the
      recurrence of collapse of previously reexpanded atelectatic lung tissue during
      general anesthesia in patients with healthy lungs. The reason for the instability
      of these lung units remains to be established. The change in the amount of
      atelectasis and shunt appears to be independent of the change in the compliance
      of the respiratory system.

PMID- 7717554
TI  - Effects of propofol sedation on seizures and intracranially recorded epileptiform
      activity in patients with partial epilepsy.
AB  - BACKGROUND: Case reports suggesting both pro- and anticonvulsant effect(s) of
      propofol have been published in recent years. The effects of sedative doses of
      propofol on epileptiform activities in patients suffering from intractable
      partial epilepsy were systematically investigated. METHODS: Fourteen patients
      suffering from complex partial seizures were studied. Electroencephalogram (EEG)
      was recorded from intracranial electrodes implanted in the hippocampi and
      temporal neocortex. Propofol was given as a computer-controlled infusion in four
      steps to achieve target plasma propofol concentrations of 0.3, 0.6, 0.9, and 1.2
      micrograms/ml. Each concentration was maintained for 30 min, and steady-state
      kinetics were confirmed by blood levels drawn at 10th and 30th min at each level.
      Between the 15th and 30th min of each concentration of propofol, EEG was analyzed
      for presence of electroencephalographic seizure activity and/or number of
      interictal spikes (IIS). Effects of propofol on IIS frequency at different
      electrode sites were compared using a two-way repeated measures analysis of
      variance. A value of P < 0.05 was considered significant. RESULTS: None of the
      patients developed a seizure during the 2 h of propofol infusion. No "false
      spikes" (spikes developing with propofol infusion in areas where no spikes were
      seen in baseline EEG) were seen. Although effects of propofol on IIS frequency
      were highly variable across patients and at different propofol doses in the same
      patient, there was no statistically significant effect of propofol on any
      electrode site with any of the doses studied. CONCLUSIONS: We were unable to
      demonstrate a significant change in epileptiform activity with sedative doses of
      propofol in patients suffering from complex partial epilepsy.

PMID- 7717555
TI  - The maximum depth of an atracurium neuromuscular block antagonized by edrophonium
      to effect adequate recovery.
AB  - BACKGROUND: The inability of edrophonium to rapidly reverse a deep
      nondepolarizing neuromuscular block may be due to inadequate dosage or a ceiling
      effect to antagonism of neuromuscular block by edrophonium. A ceiling effect
      means that only a certain level of neuromuscular block could be antagonized by
      edrophonium. Neuromuscular block greater than this could not be completely
      antagonized irrespective of the dose of edrophonium administered. The purpose of
      this study was to determine whether a ceiling effect occurred for antagonism of
      an atracurium-induced neuromuscular block by edrophonium and, if so, the maximum
      level of block that could be antagonized by edrophonium. METHODS: In 30 adult
      patients, atracurium was administered to maintain a constant neuromuscular block.
      The level of block varied between patients. Evoked adductor pollicis twitch
      tension was monitored. Incremental doses of edrophonium were administered while
      the infusion of atracurium continued. Increments were given until adequate
      recovery occurred, as defined by a train-of-four (TOF) ratio > or = 70%, or until
      no further antagonism of the block could be achieved. The probability of being
      able to effect adequate recovery by antagonism with edrophonium was determined
      using a logistic regression model. Cumulative dose-response curves were
      constructed using the logit transformation of the neuromuscular effect versus the
      logarithm of the cumulative dose of edrophonium. RESULTS: In 14 patients with a
      block of 25-77% depression of the first twitch response, antagonism by
      edrophonium to a TOF ratio > or = 70% was possible, whereas in 16 patients with a
      60-92% depression of T1, a TOF ratio > or = 70% was not achievable, indicating
      that a ceiling effect for antagonism by edrophonium occurred. A block of 67 +/-
      3% (mean +/- SE) had a 50% probability of adequate antagonism. In patients in
      whom block was antagonized to a TOF ratio < 70%, 95% of the peak antagonistic
      effect occurred with an edrophonium dose of 0.8 +/- 0.33 mg.kg-1 (mean +/- SD).
      CONCLUSIONS: There is a maximum level of neuromuscular block that can be
      antagonized by edrophonium to effect adequate recovery. The level corresponds
      approximately to the reappearance of the fourth response to TOF stimulation. It
      is probably safest to wait until this level of block occurs before edrophonium is
      given for reversal. Earlier administration will not hasten recovery.

PMID- 7717556
TI  - Cervical spine movement during laryngoscopy with the Bullard, Macintosh, and
      Miller laryngoscopes.
AB  - BACKGROUND: Direct laryngoscopy requires movement of the head, neck, and cervical
      spine. Spine movement may be limited for anatomic reasons or because of cervical
      spine injury. The Bullard laryngoscope, a rigid fiberoptic laryngoscope, may
      cause less neck flexion and head extension than conventional laryngoscopes. The
      purpose of this study was to compare head extension (measured externally),
      cervical spine extension (measured radiographically), and laryngeal view obtained
      with the Bullard, Macintosh, and Miller laryngoscopes. METHODS: Anesthesia was
      induced in 35 ASA 1-3 elective surgery patients. Patients lay on a rigid board
      with head in neutral position. Laryngoscopy was performed three times, changing
      between the Bullard, Macintosh, and Miller laryngoscopes. Head extension was
      measured with an angle finder attached to goggles worn by the patient. The best
      laryngeal view with each laryngoscope was assessed by the laryngoscopist. In
      eight patients, lateral cervical spine radiographs were taken before and during
      laryngoscopy with the Bullard and Macintosh blades. RESULTS: Median values for
      external head extension were 11 degrees, 10 degrees, and 2 degrees with the
      Macintosh, Miller, and Bullard laryngoscopy (P < 0.01), respectively. Significant
      reductions in radiographic cervical spine extension were found for the Bullard
      compared to the Macintosh blade at the atlantooccipital joint, atlantoaxial
      joint, and C3-C4. Median atlantooccipital extension angles were 6 degrees and 12
      degrees for the Bullard and Macintosh laryngoscopes, respectively. The larynx
      could be exposed in all patients with the Bullard but only in 90% with
      conventional laryngoscope (P < 0.01). CONCLUSIONS: The Bullard laryngoscope
      caused less head extension and cervical spine extension than conventional
      laryngoscopes and resulted in a better view. It may be useful in care of patients
      in whom cervical spine movement is limited or undesirable.

PMID- 7717557
TI  - Thermoregulatory vasoconstriction impairs active core cooling.
AB  - BACKGROUND: Many clinicians now consider hypothermia indicated during
      neurosurgery. Active cooling often will be required to reach target temperatures
      < 34 degrees C sufficiently rapidly and nearly always will be required if the
      target temperature is 32 degrees C. However, the efficacy even of active cooling
      might be impaired by thermoregulatory vasoconstriction, which reduces cutaneous
      heat loss and constrains metabolic heat to the core thermal compartment. The
      authors therefore tested the hypothesis that the efficacy of active cooling is
      reduced by thermoregulatory vasoconstriction. METHODS: Patients undergoing
      neurosurgical procedures with hypothermia were anesthetized with either
      isoflurane/nitrous oxide (n = 13) or propofol/fentanyl (n = 13) anesthesia. All
      were cooled using a prototype forced-air cooling device until core temperature
      reached 32 degrees C. Core temperature was measured in the distal esophagus.
      Vasoconstriction was evaluated using forearm minus fingertip skin-temperature
      gradients. The core temperature triggering a gradient of 0 degree C identified
      the vasoconstriction threshold. RESULTS: In 6 of the 13 patients given
      isoflurane, vasoconstriction (skin-temperature gradient = 0 degrees C) occurred
      at a core temperature of 34.4 +/- 0.9 degree C, 1.7 +/- 0.58 h after induction of
      anesthesia. Similarly, in 7 of the 13 patients given propofol, vasoconstriction
      occurred at a core temperature of 34.5 +/- 0.9 degree C, 1.6 +/- 0.6 h after
      induction of anesthesia. In the remaining patients, vasodilation continued even
      at core temperatures of 32 degrees C. Core cooling rates were comparable in each
      anesthetic group. However, patients in whom vasodilation was maintained cooled
      fastest. Patients in whom vasoconstriction occurred required nearly an hour
      longer to reach core temperatures of 33 degrees C and 32 degrees C than did those
      in whom vasodilation was maintained (P < 0.01). CONCLUSIONS: Vasoconstriction did
      not produce a full core temperature "plateau," because of the extreme
      microenvironment provided by forced-air cooling. However, it markedly decreased
      the rate at which hypothermia developed. The approximately 1-h delay in reaching
      core temperatures of 33 degrees C and 32 degrees C could be clinically important,
      depending on the target temperature and the time required to reach critical
      portions of the operation.

PMID- 7717558
TI  - Does spinal anesthesia result in a more complete sympathetic block than that from
      epidural anesthesia?
AB  - BACKGROUND: Spinal and epidural injection of local anesthetics are used to
      produce sympathetic block to diagnose and treat certain chronic pain syndromes.
      It is not clear whether either form of regional anesthesia produces a complete
      sympathetic block. Spinal anesthesia using tetracaine has been reported to
      produce a decrease in plasma catecholamine concentrations. This has not been
      demonstrated for epidural anesthesia in humans with level of anesthesia below C8.
      One possible explanation is that spinal anesthesia results in a more complete
      sympathetic block than epidural anesthesia. To examine this question, a cross
      over study was performed in young, healthy volunteers. METHODS: Ten subjects
      underwent both spinal and epidural anesthesia with lidocaine (plain) on the same
      day with complete recovery between blocks. By random assignment, spinal
      anesthesia and epidural anesthesia were induced via lumbar injection. Before and
      30 min after local anesthetic injection, a cold pressor test (CPT) was performed.
      Blood was obtained to determine epinephrine and norepinephrine plasma
      concentrations at four stages: (1) 20 min after placing peripheral catheters, (2)
      at the end of a 2-min CPT (before conduction block), (3) 30 min after injection
      of epidural or spinal lidocaine, and (4) at the end of a second CPT (during
      anesthesia). Mean arterial pressure, heart rate, noninvasive cardiac index, and
      analgesia to pin-prick were monitored. RESULTS: Neither spinal nor epidural
      anesthesia changed baseline resting values of catecholamines or any hemodynamic
      variable, except heart rate, which was slightly decreased during spinal
      anesthesia. Median level of analgesia was T4 during spinal and T3 during epidural
      anesthesia. CPT before conduction block reliably increased heart rate, mean
      arterial pressure, cardiac index, epinephrine, and norepinephrine. Conduction
      block attenuated the increase in response to CPT only in mean arterial pressure
      (spinal and epidural) and cardiac index (spinal only). Neither technique blocked
      the increase in heart rate, norepinephrine, or epinephrine to CPT. CONCLUSIONS:
      Spinal anesthesia did not result in a more complete attenuation of the
      sympathetic response to a CPT than did epidural anesthesia. In response to the
      CPT, spinal anesthesia blocked the increase in cardiac index, and epidural
      anesthesia resulted in a decrease in total peripheral resistance compared to the
      pre-anesthesia state. The differences between the techniques are not significant
      and are of uncertain clinical implications.

PMID- 7717559
TI  - Effects of propofol or isoflurane anesthesia on cardiac conduction in children
      undergoing radiofrequency catheter ablation for tachydysrhythmias.
AB  - BACKGROUND: To determine suitability for ablation procedures in children, two
      commonly used anesthetic agents were studied: propofol and isoflurane. METHODS:
      Twenty patients presenting for a radiofrequency catheter ablation procedure were
      included and randomly assigned to two groups. A baseline electrophysiology study
      was performed during anesthesia with thiopental, alfentanil, nitrous oxide, and
      pancuronium in all patients. At the completion of the baseline electrophysiology
      study (EPS), 0.8-1.2% isoflurane was administered to patients in group 1 and 2
      mg/kg propofol bolus plus an infusion of 150 micrograms.kg-1.min-1 was
      administered to patients in group 2. Nitrous oxide and pancuronium were used
      throughout the procedure. After 30 min of equilibration, both groups underwent a
      repeat EPS. The following parameters were measured during the EPS: cycle length,
      atrial-His interval, His-ventricle interval, corrected sinus node recovery time,
      AV node effective refractory period, and atrial effective refractory period.
      Using paired t tests, the electrophysiologic parameters described above measured
      during propofol or isoflurane anesthesia were compared to those measured during
      baseline anesthesia. Statistical significance was accepted as P < 0.05. RESULTS:
      There was no statistically significant difference in the results obtained during
      baseline anesthesia when compared with those measured during propofol or
      isoflurane anesthesia. CONCLUSIONS: Neither propofol nor isoflurane anesthesia
      alter sinoatrial or atrioventricular node function in pediatric patients
      undergoing radiofrequency catheter ablation, compared to values obtained during
      baseline anesthesia with alfentanil and midazolam.

PMID- 7717560
TI  - Propofol has no direct effect on sinoatrial node function or on normal
      atrioventricular and accessory pathway conduction in Wolff-Parkinson-White
      syndrome during alfentanil/midazolam anesthesia.
AB  - BACKGROUND: Propofol has been implicated as causing intraoperative
      bradyarrhythmias. Furthermore, the effects of propofol on the electrophysiologic
      properties of the sinoatrial (SA) node and on normal atrioventricular (AV) and
      accessory pathways in patients with Wolff-Parkinson-White syndrome are unknown.
      Therefore, this study examined the effects of propofol on the cardiac
      electrophysiologic properties in humans to determine whether propofol promotes
      bradyarrhythmias and its suitability as an anesthetic agent in patients
      undergoing ablative procedures. METHODS: Twelve patients with Wolff-Parkinson
      White syndrome undergoing radiofrequency catheter ablation were studied.
      Anesthesia was induced with alfentanil (50 micrograms/kg), midazolam (0.15
      mg/kg), and vecuronium (20 mg) and maintained with alfentanil (2 micrograms.kg
      1.min-1) and midazolam (1-2 mg, every 15 min, as needed). A electrophysiologic
      study was performed consisting of measurement of the effective refractory period
      of the right atrium, AV node, and accessory pathway and the shortest cycle length
      of the AV node and accessory pathway during antegrade stimulation plus the
      effective refractory period of the right ventricle and accessory pathway and the
      shortest cycle length of the accessory pathway during retrograde stimulation.
      Determinants of SA node function including sinus node recovery time, corrected
      sinus node recovery time, and SA conduction time; intraatrial conduction time and
      atrial-His interval also were measured. Reciprocating tachycardia was induced by
      rapid right atrial or ventricular pacing, and the cycle length and atrial-His,
      His-ventricular, and ventriculoatrial intervals were measured.
      Alfentanil/midazolam was then discontinued. Propofol was administered (bolus 2
      mg/kg + 120 micrograms.kg-1.min-1), and the electrophysiologic measurements were
      repeated. RESULTS: Propofol caused a statistically significant but clinically
      unimportant prolongation of the right atrial refractory period. The effective
      refractory periods of the AV node, right ventricle, and accessory pathway, as
      well as the shortest cycle length, were not affected. Parameters of SA node
      function and intraatrial conduction also were not affected. Sustained
      reciprocating tachycardia was inducible in 8 of 12 patients, and propofol had no
      effect on its electrophysiologic properties. All accessory pathways were
      successfully identified and ablated. CONCLUSIONS: Propofol has no clinically
      significant effect on the electrophysiologic expression of the accessory pathway
      and the refractoriness of the normal AV conduction system. In addition, propofol
      has no direct effect on SA node activity or intraatrial conduction; therefore, it
      does not directly induce bradyarrhythmias. It is thus a suitable agent for use in
      patients undergoing ablative procedures who require either a neuroleptic or
      general anesthetic.

PMID- 7717561
TI  - Analysis of statistical tests to compare visual analog scale measurements among
      groups.
AB  - BACKGROUND: A common type of study performed by anesthesiologists determines the
      effect of an intervention on pain reported by groups of patients. The goal of
      this study was to evaluate the effectiveness of t, analysis of variance (ANOVA),
      Mann-Whitney, and Kruskal-Wallis tests to compare visual analog scale (VAS)
      measurements between two or among three groups of patients. These results may be
      particularly helpful during the design of studies that measure pain with a VAS.
      METHODS: One VAS measurement was obtained from each of 480 nulliparous women in
      labor who were receiving oxytocin (149), nalbuphine (159), or epidural
      bupivacaine (172). Multiple simulated samples were then drawn from these data.
      These simulated samples were used in computer simulations of clinical trials
      comparing VAS measurements among groups. t and ANOVA tests were performed before
      and after an arcsin transformation was used, to make the data closer to a normal
      distribution. VAS measurements were also compared after they were divided into
      five ranked categories. RESULTS: The statistical distributions of VAS
      measurements were not normal (P < 10(-7)). Arcsin transformation made the
      distributions closer to normal distributions. Nevertheless, no statistical test
      incorrectly suggested that a difference existed among groups, when there was no
      difference, more often than the expected rate. t or ANOVA tests had a slightly
      greater statistical power than the other tests to detect differences among
      groups. Because arcsin transformation both decreased differences among means and
      reduced the variance to a lesser extent, it decreased power to detect differences
      among groups. Statistical power to detect differences among groups was not less
      for a five-category VAS than for a continuous VAS. CONCLUSIONS: We conclude that
      t and ANOVA, without an accompanying arcsin transformation, are good tests to
      find differences in VAS measurements among groups.

PMID- 7717562
TI  - Weekly ventilator circuit changes. A strategy to reduce costs without affecting
      pneumonia rates.
AB  - BACKGROUND: Mechanical ventilator circuits are commonly changed at 48-h
      intervals. This frequency may be unnecessary because ventilator-associated
      pneumonia often results from aspiration of pharyngeal secretions and not from the
      ventilator circuit. We compared the ventilator-associated pneumonia rates and
      costs associated with 48-h and 7-day circuit changes. METHODS: Ventilator
      circuits were changed at 48-h intervals during the control period (November 1992
      to April 1993) and at 7-day intervals during the study period (June 1993 to
      November 1993). Nosocomial pneumonias were prospectively identified using the
      criteria of the Centers for Disease Control and Prevention. The annual cost
      difference of changing circuits at 48-h and 7-day intervals was calculated using
      the distribution of ventilator days for the control and study periods. RESULTS:
      There were 1,708 patients, 9,858 ventilator days, and a pneumonia rate of 9.64
      per 1,000 ventilator days in the control group (48-h circuit changes). There were
      1,715 patients, 9,160 ventilator days, and 8.62 pneumonias per 1,000 ventilator
      days when circuits were changed at 1-week intervals (study group). Using a
      logistic regression model, there were significantly greater odds of developing a
      ventilator-associated pneumonia in surgical patients (odds ratio 1.77, P = 0.02)
      and patients in critical care units (odds ratio 1.54, P = 0.05), but no
      significant risk of ventilator-associated pneumonia in patients in whom circuits
      were changed at 1-week intervals (odds ratio 0.82, P = 0.22). Changing circuits
      at 7-day intervals resulted in a 76.6% ($111,530) reduction in the annual cost
      for materials and salaries. CONCLUSIONS: We found no difference in pneumonia
      rates with ventilator circuit changes at 48-h and 7-day intervals. Ventilator
      circuits can be safely changed at weekly intervals, resulting in large cost
      savings.

PMID- 7717564
TI  - A comparison of baroreflex sensitivity during isoflurane and desflurane
      anesthesia in humans.
AB  - BACKGROUND: Desflurane anesthesia has been associated with heart rate (HR) and
      sympathetic nerve activity (SNA) responses that differ from those during
      isoflurane anesthesia. Whether these differences might be due to better
      preservation by desflurane of the baroreceptor reflex control of HR or SNA in
      humans was examined. METHODS: Baroreflex sensitivity was assessed in 18
      volunteers anesthetized with either desflurane or isoflurane. Measurements of HR,
      blood pressure (BP), and efferent SNA (percutaneous recordings from the peroneal
      nerve) were made, and baroreflex sensitivity was evaluated at conscious baseline
      and during 0.5, 1.0, and 1.5 MAC anesthesia. Baroreflex responses were triggered
      by bolus intravenous injections of nitroprusside (100 micrograms) and
      phenylephrine (150 micrograms). The linear portions of the baroreflex curves
      relating HR to mean arterial pressure and relating SNA to diastolic pressure were
      determined to obtain cardiac and sympathetic baroslopes, respectively. RESULTS:
      Cardiac (HR) baroslopes were equally diminished at increasing MAC of both
      anesthetics. Sympathetic baroslopes were preserved at 0.5 MAC isoflurane but
      diminished at 0.5 MAC desflurane. Higher MAC produced equal depression of
      sympathetic baroslopes with both anesthetics. CONCLUSIONS: Increasing MAC of
      desflurane and isoflurane anesthesia results in similar and progressive decreases
      in BP but dissimilar SNA and HR responses. These differences are not explained by
      disparate effects of these anesthetics on the baroreceptor reflex control of SNA
      or HR.

PMID- 7717563
TI  - Edrophonium increases mivacurium concentrations during constant mivacurium
      infusion, and large doses minimally antagonize paralysis.
AB  - BACKGROUND: Mivacurium, a nondepolarizing muscle relaxant, is metabolized by
      plasma cholinesterase. Although edrophonium does not alter plasma cholinesterase
      activity, we have observed that doses of edrophonium that antagonize paralysis
      from other nondepolarizing muscle relaxants are less effective with mivacurium.
      We speculated that edrophonium might after metabolism of mivacurium, thereby
      hindering antagonism of paralysis. Accordingly, we determined the effect of
      edrophonium on neuromuscular function and plasma mivacurium concentrations during
      constant mivacurium infusion. METHODS: We infused mivacurium to maintain 90%
      depression of adductor pollicis twitch tension and then gave edrophonium in doses
      ranging from 125-2,000 micrograms/kg without altering the mivacurium infusion.
      Peak twitch tension after edrophonium was determined to estimate the dose of
      edrophonium antagonizing 50% of twitch depression for antagonism of mivacurium;
      plasma cholinesterase activity and mivacurium concentrations before and after
      edrophonium were measured. Additional subjects were given 500 micrograms/kg
      edrophonium to antagonize continuous infusions of d-tubocurarine and vecuronium.
      RESULTS: With mivacurium, edrophonium increased twitch tension in a dose
      dependent manner: the dose of edrophonium antagonizing 50% of twitch depression
      was 2,810 micrograms/kg. The largest dose of edrophonium (2,000 micrograms/kg)
      produced only 45 +/- 7% antagonism. Edrophonium, 500 micrograms/kg, antagonized
      mivacurium markedly less than it antagonized d-tubocurarine and vecuronium.
      Edrophonium increased plasma concentrations of the two potent stereoisomers of
      mivacurium 48% and 79%, these peaking at 1-2 min; plasma cholinesterase activity
      was unchanged. CONCLUSIONS: Edrophonium doses that antagonize d-tubocurarine and
      vecuronium are less effective in antagonizing the neuromuscular effects of
      mivacurium during constant infusion. Edrophonium increases plasma mivacurium
      concentrations, partly or completely explaining its limited efficacy; the
      mechanism by which edrophonium increases mivacurium concentrations remains
      unexplained. Our results demonstrate that antagonism of mivacurium by edrophonium
      is impaired, and therefore we question whether edrophonium should be used to
      antagonize mivacurium.

PMID- 7717565
TI  - Myocyte contractile responsiveness after hypothermic, hyperkalemic cardioplegic
      arrest. Disparity between exogenous calcium and beta-adrenergic stimulation.
AB  - BACKGROUND: Acute left ventricular dysfunction is commonly encountered after
      hypothermic, hyperkalemic cardioplegic arrest (HHCA) and often requires inotropic
      intervention for successful separation from cardiopulmonary bypass. However, the
      basic mechanisms involved in depressed left ventricular function and the cellular
      basis for the differential effects of inotropic drugs after HHCA are unknown.
      Accordingly, the goal of this study was to determine the effects of calcium
      (Ca2+) and beta-adrenergic receptor agonists (beta AR) stimulation on isolated
      myocyte contractile function after HHCA. METHODS: Myocytes were isolated from the
      left ventricle of nine pigs and randomly assigned to one of the following
      treatment groups: (1) normothermic, control: incubation in oxygenated cell
      culture media for 2 h at 37 degrees C; and (2) cardioplegia: incubation in 4
      degrees C crystalloid cardioplegia for 2 h, followed by rewarming. Steady-state
      myocyte contractile function was measured after pulse stimulation at baseline, in
      the presence of extracellular Ca2+ (3-10 mM), and in the presence of the beta AR
      agonist isoproterenol (2-100 nM). Myocyte profile surface area was measured for
      both normothermic myocytes and myocytes after HHCA. In a separate set of
      experiments, myocyte contractile function also was documented after 2 h of
      hypoxic conditions with both normothermic incubation and HHCA, in the presence
      and absence of beta AR stimulation. RESULTS: Baseline myocyte contractile
      function was significantly less in the cardioplegia group compared to control.
      Extracellular Ca2+ produced a dose-dependent significant increase in myocyte
      contractile function in the normothermic control group, whereas increased
      extracellular Ca2+ only minimally increased myocyte contractile function in the
      cardioplegia group. A dose-dependent, significant increase in myocyte contractile
      function was observed in both groups after beta AR stimulation by isoproterenol;
      however, myocyte contractile function in the cardioplegia group was decreased
      compared to the control group. Hypoxia under normothermic conditions
      significantly reduced myocyte contractile function, myocyte relaxation, and beta
      adrenergic responsiveness. Hypoxia in combination with cardioplegic arrest
      compounded the negative effects on contractile processes but did not further
      impair beta-adrenergic responsiveness. Myocyte profile surface area was
      significantly increased after HHCA. CONCLUSIONS: The minimal improvement in
      myocyte contractile function after HHCA with increased extracellular Ca2+
      suggests that Ca2+ depletion is not the primary mechanism for depressed myocyte
      contractility after HHCA. On the other hand, because beta AR administration
      improved myocyte contractile function after HHCA, the cellular basis for the
      effects of beta AR stimulation after HHCA is probably not increased myocyte Ca2+
      but rather alternative mechanisms, such as changes in myofilament sensitivity to
      Ca2+. These results also suggest that the abnormalities in left ventricular
      function after HHCA result from the direct effects of hyperkalemic induced
      electromechanical uncoupling as well as relative hypoxic conditions.

PMID- 7717566
TI  - Arterial oxygenation during one-lung ventilation. A comparison of enflurane and
      isoflurane.
AB  - BACKGROUND: Because maintaining arterial oxygenation (PaO2) during one-lung
      ventilation (OLV) can be a clinical problem, it is useful to be aware of factors
      that influence PaO2 in this situation and are under the control of the
      anesthesiologist. It is unknown whether, among the commonly used volatile
      anesthetic agents, one is associated with higher PaO2 levels. Clinical studies
      suggest that isoflurane provides superior PaO2 during OLV than does halothane.
      These have not been compared to enflurane. The authors studied PaO2 and
      hemodynamics during OLV with 1 MAC enflurane versus 1 MAC isoflurane. METHODS:
      Twenty-eight adults who had prolonged periods of OLV anesthesia with minimal
      trauma to the nonventilated lung (thoracoscopic or esophageal surgery) were
      studied in a cross-over design. Patients were randomized to two groups: Group 1
      received 1 MAC enflurane in oxygen from induction until after the first 30 min of
      OLV, then were switched to 1 MAC isoflurane. In group 2, the order of the
      anesthetics was reversed. RESULTS: Isoflurane was associated with higher PaO2
      values during OLV (P < 0.0001). Mean PaO2 (+/- SD) after 30 min OLV isoflurane
      was 231 (+/- 125) mmHg versus 184 (+/- 106) mmHg after 30 min OLV enflurane. The
      difference in PaO2 between the two anesthetics was most marked in the patients
      with the highest PaO2 during OLV: PaO2 isoflurane PaO2 enflurane varies; is
      directly proportional to PaO2 isoflurane (r = 0.65, P < 0.001). There were no
      other significant differences between anesthetic gases in the measured
      hemodynamic or respiratory variables. In the subgroup of patients with pulmonary
      artery catheters (n = 7), PaO2 correlated with cardiac output during OLV for both
      anesthetics (r = 0.81, P < 0.001). CONCLUSIONS: During OLV, the PaO2 values with
      1 MAC isoflurane were greater than those with enflurane. The dependence of PaO2
      on cardiac output does not support the hypothesis that an increase in cardiac
      output will cause a decrease in hypoxic pulmonary vasoconstriction and a decrease
      in PaO2 during OLV.

PMID- 7717567
TI  - Abnormal action potential responses to halothane in heart muscle isolated from
      malignant hyperthermia-susceptible pigs.
AB  - BACKGROUND: During human and porcine malignant hyperthermia (MH), cardiac
      dysrhythmias and altered myocardial function can be observed. It is unknown
      whether a primary abnormality in cardiac muscle contributes to the cardiac
      symptoms during MH. An abnormal response to halothane has recently been
      demonstrated in action potentials (APs) from MH-susceptible (MHS) human skeletal
      muscles. We investigated the electrophysiologic properties in trabeculae isolated
      from the right ventricles of normal (MHN) and MHS pigs. METHODS: The experiments
      were performed on electrically stimulated (1 Hz) trabeculae isolated from the
      right ventricles of MHS and MHN pigs. Resting membrane potentials, APs, and
      tension were measured with and without the presence of 1% halothane. In addition,
      the halothane-equilibrated muscles were exposed to caffeine in increasing doses
      (1, 2, and 4 mM). RESULTS: In the absence of halothane, resting potential and AP
      characteristics in MHS and MHN muscles did not differ significantly. Halothane
      did not alter resting potentials but produced different alterations in the APs in
      MHS and MHN muscles, whereas the decrease in twitch tension was identical. In
      contrast to reductions in the AP amplitude and duration in MHN muscle, halothane
      produced an enlargement of the APs in MHS muscle. The addition of caffeine caused
      nearly identical prolongations of AP duration in MHS and MHN muscles.
      CONCLUSIONS: This in vitro study demonstrates that halothane produces abnormal
      alterations in the dynamic electric properties of the ventricular excitable
      membrane from MHS pigs. These results suggest a latent defect in the myocardium
      of MHS pigs that becomes apparent in the presence of MH-triggering agents.

PMID- 7717568
TI  - Desensitization to the behavioral effects of alpha 2-adrenergic agonists in rats.
AB  - BACKGROUND: The analgesic and sedative-hypnotic utility of the alpha 2 agonists
      clonidine and dexmedetomidine are currently being investigated. Both compounds
      exert their behavioral responses by activating central alpha 2 adrenoceptors,
      albeit with different selectivities and efficacies. Furthermore, the analgesic
      and hypnotic behavioral responses are produced at different sites and may be
      affected independently of one another. A series of studies was conducted in rats
      to determine (1) whether tolerance and cross-tolerance develop to the analgesic
      actions of clonidine or dexmedetomidine; (2) how the number of available alpha 2
      adrenoceptors affects the analgesic response to dexmedetomidine and clonidine;
      and (3) how the number of available alpha 2 adrenoceptor affects the hypnotic
      response to dexmedetomidine. METHODS: Rats were administered equianalgesic doses
      of dexmedetomidine or clonidine continuously, subcutaneously by osmotic
      minipumps. After 7 days the analgesic response to acutely administered
      dexmedetomidine or clonidine at median effective analgesic doses was assessed by
      the tail-flick latency response. The number of alpha 2 adrenoceptors in the
      spinal cord was diminished in a dose-dependent manner by covalent modification
      with a noncompetitive receptor blocker, N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline (EEDQ). Recovery of the tail-flick latency response to clonidine
      and dexmedetomidine was determined and correlated to the recovery of receptor
      density as assessed by radiolabeled-ligand binding studies. The alpha 2
      adrenoceptor population in the locus ceruleus of rats was depleted with EEDQ, and
      recovery of the hypnotic response (as assessed by the loss of righting reflex) to
      dexmedetomidine was determined and correlated to the recovery of receptor
      density. RESULTS: After 7 days of chronic treatment with dexmedetomidine,
      analgesic responses to dexmedetomidine and clonidine remained unaltered. However,
      chronic treatment with clonidine significantly decreased the analgesic effect of
      clonidine, whereas the analgesic effect to dexmedetomidine was unaffected. In the
      EEDQ experiments, the analgesic response to dexmedetomidine was restored to
      normal when 44% of the alpha 2 adrenoceptors in the spinal cord were available
      for agonist binding; comparatively more alpha 2 adrenoceptors (77%) were required
      for the analgesic response to clonidine to be restored. The recovery of the
      hypnotic response to dexmedetomidine after EEDQ treatment was retarded when
      compared with the recovery of the analgesic response to that compound. Greater
      than 77% of alpha 2 adrenoceptors in the locus ceruleus must be available for the
      hypnotic response to alpha 2 agonists to be expressed. CONCLUSIONS: Fewer alpha 2
      adrenoceptors need to be available for analgesia to be produced by
      dexmedetomidine compared with the number required for analgesia by clonidine.
      This difference should result in less tolerance in the analgesic response to
      dexmedetomidine than to clonidine with chronic use. Dexmedetomidine requires
      fewer alpha 2 adrenoceptors to elicit an analgesic response than it does to
      elicit a hypnotic response. Thus the analgesic properties of alpha 2-adrenergic
      agonists persist after the hypnotic response has been attenuated after chronic
      alpha 2 agonist administration.

PMID- 7717569
TI  - Glycine receptor antagonism. Effects of ACEA-1021 on the minimum alveolar
      concentration for halothane in the rat.
AB  - BACKGROUND: Glycine and glutamate binding sites are allosterically coupled at the
      N-methyl-D-aspartate (NMDA) receptor complex. Previous studies have shown that
      antagonism of glutamate at the NMDA receptor reduces the minimum alveolar
      concentration (MAC) for volatile anesthetics. 5-Nitro-6,7-dichloro-2,3
      quinoxalinedione (ACEA-1021) is a competitive antagonist at the glycine
      recognition site of the NMDA receptor. The purpose of this study was to determine
      whether glycine receptor antagonism also reduces volatile anesthetic requirements
      in the rat. METHODS: In experiment 1, Sprague-Dawley rats were anesthetized with
      halothane in 50% O2-balance N2 and their lungs mechanically ventilated. They were
      randomly assigned to one of three groups according to the dose of ACEA-1021
      administered (0, 20, or 40 mg/kg intravenously; n = 6). The bolus dose of ACEA
      1021 was followed by a continuous intravenous infusion of vehicle or ACEA-1021 at
      14 mg.kg-1.h-1. Halothane MAC was then determined by the tail-clamp method. In
      experiment 2, awake rats were randomly assigned to groups according to the same
      dosages of ACEA-1021 as in experiment 1. Arterial CO2 tension and mean arterial
      pressure were recorded before and 5 and 30 min after the start of the infusion.
      The infusion was then stopped, and the time to recovery of the righting reflex
      was recorded. RESULTS: In experiment 1, ACEA-1021 decreased halothane MAC (mean
      +/- SD) in a dose-dependent manner (control, 0.95 +/- 0.15 vol%; ACEA-1021 20
      mg/kg, 0.50 +/- 0.14 vol%; ACEA-1021 40 mg/kg, 0.14 +/- 0.16 vol%; P < 0.01). In
      experiment 2, arterial CO2 tension was increased by ACEA-1021 (control, 38 +/- 3
      mmHg; ACEA-1021 20 mg/kg, 43 +/- 3 mmHg; ACEA-1021 40 mg/kg, 48 +/- 2 mmHg; P <
      0.01). Mean arterial pressure was not affected by any dose of ACEA-1021. The
      righting reflex was abolished in rats receiving ACEA-1021 40 mg/kg only and
      recovered 30 +/- 7 min after discontinuation of the infusion. CONCLUSIONS:
      Halothane MAC reduction by glycine receptor antagonism was greater than that
      previously observed for antagonism of glutamate at the NMDA or AMPA receptor. In
      rats receiving ACEA-1021 only, minimal hemodynamic depression and moderate
      hypoventilation were observed. Antagonism of glycine at the NMDA receptor
      recognition site offers a potential mechanism of action of anesthesia.

PMID- 7717570
TI  - Positive end-expiratory pressure ventilation elicits increases in endogenously
      formed nitric oxide as detected in air exhaled by rabbits.
AB  - BACKGROUND: Nitric oxide (NO) formed from L-arginine is exhaled by mammals and
      regulates pulmonary vascular tone. Little is known about how its formation is
      stimulated. METHODS: The concentration of NO in exhaled air was monitored by
      chemiluminescence in pentobarbital-anesthetized rabbits receiving mechanical
      ventilation by tracheostomy with graded positive end-expiratory pressure (PEEP).
      RESULTS: Introduction of PEEP (2.5-15 cmH2O) elicited dose-dependent and
      reproducible increments in exhaled NO and in arterial oxygen tension (PaO2). The
      increase in exhaled NO exhibited a biphasic pattern, with an initial peak
      followed by a partial reversal during the 4-min period at each level of PEEP.
      Thus, at a PEEP of 10 cmH2O, exhaled NO initially increased from 19 +/- 4 to 30
      +/- 5 parts per billion (ppb) (P < 0.001, n = 9) and then decreased to 27 +/- 5
      ppb (P < 0.005) at the end of the 4-min observation period. Simultaneously, PaO2
      increased from 75 +/- 12 mmHg in the control situation to 105 +/- 11 mmHg (P <
      0.05) at a PEEP of 10 cmH2O. After bilateral vagotomy, including bilateral
      transection of the depressor nerves, the increase in exhaled NO in response to
      PEEP was significantly reduced (P < 0.01). Thus, after vagotomy, a PEEP of 10
      cmH2O elicited an increase in the concentration of exhaled NO from 13 +/- 3 to 17
      +/- 3 ppb (n = 7). Vagotomy did not affect the baseline concentration of NO in
      exhaled air. The PEEP-induced increments in PaO2 were not affected by the NO
      synthase inhibitor L-N omega-arginine-methylester (30 mg.kg-1 intravenously). In
      open-chest experiments, PEEP (10 cmH2O) induced a reduction in cardiac output
      from 317 +/- 36 to 235 +/- 30 ml.min-1 and an increase in exhaled NO from 23 +/-
      6 to 30 +/- 7 ppb (P < 0.05, n = 5). Reduction in cardiac output from 300 +/- 67
      to 223 +/- 52 ml.min-1 by partial obstruction of the pulmonary artery did not
      significantly increase exhaled NO (from 23 +/- 7 to 25 +/- 6, difference not
      significant; n = 3). CONCLUSIONS: PEEP elicited increments in exhaled NO, perhaps
      by a stretch-dependent effect on the respiratory system. This finding may be
      attributed in part to a vagally influenced mechanism.

PMID- 7717571
TI  - Microcirculatory perfusion during volume therapy. A comparative study using
      crystalloid or colloid in awake animals.
AB  - BACKGROUND: Because of the passage of water and salt molecules into the
      interstitial space, volume replacement with crystalloid solutions requires an
      amount at least four times that of lost blood. The resulting tissue edema may
      interfere with nutritive capillary perfusion and oxygen delivery. To prove this
      hypothesis, the effects of isovolemic hemodilution (hematocrit 30%) with Ringer's
      lactate solution or dextran 60 on tissue perfusion and oxygenation were
      investigated in awake Syrian golden hamsters. METHODS: Experiments were performed
      by using a chronic dorsal skinfold window giving access to skeletal muscle tissue
      (musculus cutaneus) with in vivo microscopy, quantitative video image analysis,
      and surface oxygen partial pressure electrodes. Central venous and arterial
      pressures were measured by means of chronically implanted jugular venous and
      carotid catheters. RESULTS: Isovolemic exchange of blood with dextran caused no
      significant changes in arterial or central venous pressure, heart rate, capillary
      flow velocity, functional capillary density, or surface oxygen partial pressure
      during the 1-h observation period. A volume of Ringer's solution equal to four
      times of the amount of blood lost maintained arterial pressure and heart rate
      when central venous pressure was kept at predilution control values. However,
      tissue perfusion determined by counting perfused capillaries per terminal
      arteriole was reduced by 62%, and mean tissue oxygen partial pressure decreased
      from 19 to 8 mmHg. CONCLUSIONS: In this model, volume replacement with artificial
      colloids yielded hemodynamic stability and adequate tissue oxygen supply, whereas
      administration of crystalloids alone jeopardized tissue perfusion and
      oxygenation.

PMID- 7717574
TI  - Proceedings of the 24th Conference of the International Society for Animal
      Genetics. Prague, Czech Republic, 23-29 July 1994. Abstracts.

PMID- 7717573
TI  - Isoflurane reduces ischemia-induced glutamate release in rats subjected to
      forebrain ischemia.
AB  - BACKGROUND: The release of excitatory neurotransmitters during ischemia is
      thought to contribute to ischemic neuronal injury. Volatile anesthetics have been
      shown to reduce excitatory neurotransmission in vitro, and it is conceivable that
      they reduce ischemia-induced neurotransmitter release. The current investigation
      was conducted to evaluate the effect of isoflurane and N2O-fentanyl anesthesia on
      ischemia-induced glutamate release in the rat and to compare it with that of mild
      hypothermia, an intervention known to reduce glutamate release significantly.
      METHODS: Microdialysis probes were implanted into the parietal cortex and dorsal
      hippocampus of four groups of anesthetized rats (n = 5 per group). The
      hypothermic group was anesthetized with 1.2% halothane. The two isoflurane groups
      were anesthetized with 0.5 minimum alveolar concentration or
      electroencephalographic burst-suppression doses of isoflurane (approximately 2
      minimum alveolar concentration). The control group was anesthetized with 70% N2O
      30% O2 and fentanyl. The pericranial temperature was maintained at 34 degrees C
      in the hypothermic group and at 38 degrees C in the remaining groups. Ischemia
      was induced by bilateral carotid artery occlusion with simultaneous hypotension
      to 35 mmHg for 10 min, followed by a reperfusion period of 70 min. Dialysate was
      collected before, during, and after ischemia. The concentrations of glutamate and
      glycine in the dialysate were measured by high-performance liquid chromatography.
      RESULTS: Preischemic glutamate and glycine concentrations in the dialysate were
      similar among the groups. Ischemia resulted in a significant increase in
      glutamate and glycine concentrations in the N2O-fentanyl groups in the parietal
      cortex and in the hippocampus. This increase in neurotransmitter concentrations
      did not occur in the hypothermic group in either structure. Isoflurane reduced
      glutamate concentrations in both structures and glycine concentrations in the
      hippocampus. In the parietal cortex, glycine concentrations did not increase in
      either isoflurane group. CONCLUSIONS: Hypothermia inhibits ischemia-induced
      excitatory neurotransmitter release in the rat. Isoflurane, in comparison with a
      N2O-fentanyl-anesthetized state, significantly attenuates excitatory
      neurotransmitter release in the hippocampus. This effect of isoflurane is
      comparable to that of mild hypothermia.

PMID- 7717572
TI  - pH-stat management reduces the cerebral metabolic rate for oxygen during profound
      hypothermia (17 degrees C). A study during cardiopulmonary bypass in rabbits.
AB  - BACKGROUND: Greater cerebral metabolic suppression may increase the brain's
      tolerance to ischemia. Previous studies examining the magnitude of metabolic
      suppression afforded by profound hypothermia suggest that the greater arterial
      carbon dioxide tension of pH-stat management may increase metabolic suppression
      when compared with alpha-stat management. METHODS: New Zealand White rabbits,
      anesthetized with fentanyl and diazepam, were maintained during cardiopulmonary
      bypass (CPB) at a brain temperature of 17 degrees C with alpha-stat (group A, n =
      9) or pH-stat (group B, n = 9) management. Measurements of brain temperature,
      systemic hemodynamics, arterial and cerebral venous blood gases and oxygen
      content, cerebral blood flow (CBF) (radiolabeled microspheres), and cerebral
      metabolic rate for oxygen (CMRO2) (Fick) were made in each animal at 65 and 95
      min of CPB. To control for arterial pressure and CBF differences between
      techniques, additional rabbits underwent CPB at 17 degrees C. In group C (alpha
      stat, n = 8), arterial pressure was decreased with nitroglycerin to values
      observed with pH-stat management. In group D (pH-stat, n = 8), arterial pressure
      was increased with angiotensin II to values observed with alpha-stat management.
      In groups C and D, CBF and CMRO2 were determined before (65 min of CPB) and after
      (95 min of CPB) arterial pressure manipulation. RESULTS: In groups A (alpha-stat)
      and B (pH-stat), arterial pressure; hemispheric CBF (44 +/- 17 vs. 21 +/- 4
      ml.100 g-1.min-1 [median +/- quartile deviation]; P = 0.017); and CMRO2 (0.54 +/-
      0.13 vs. 0.32 +/- 0.10 ml O2 x 100 g-1.min-1; P = 0.0015) were greater in alpha
      stat than in pH-stat animals, respectively. As a result of arterial pressure
      manipulation, in groups C (alpha-stat) and D (pH-stat) neither arterial pressure
      (75 +/- 2 vs. 78 +/- 2 mmHg) nor hemispheric CBF (40 +/- 10 vs. 48 +/- 6 ml.100 g
      1.min-1; P = 0.21) differed between alpha-stat and pH-stat management,
      respectively. Nevertheless, CMRO2 was greater in alpha-stat than in pH-stat
      animals (0.71 +/- 0.10 vs. 0.45 +/- 0.10 ml O2 x 100g-1.min-1, respectively; P =
      0.002). CONCLUSIONS: At 17 degrees C, CMRO2 with pH-stat management is 35-40%
      less than that with alpha-stat management and is independent of CBF or arterial
      pressure differences between the techniques.

PMID- 7717575
TI  - Serum swainsonine concentration and alpha-mannosidase activity in cattle and
      sheep ingesting Oxytropis sericea and Astragalus lentiginosus (locoweeds).
AB  - Serum alpha-mannosidase activity and swainsonine concentration were determined in
      4 cattle and 15 sheep (3 groups of 5 each) that were administered ground locoweed
      (Oxytropis sericea or Astragalus lentiginosus) containing swainsonine at dosages
      of approximately 0.8 mg/kg of body weight/d (cows, 30 days each) and 0, 1.0, and
      1.5 mg/kg/d (sheep, 11 days each). The cattle developed mild clinical signs of
      locoism, including signs of depression, lethargy, and slight intention tremors.
      Clinical signs of toxicosis were not observed in the sheep. Within 24 hours of
      initial treatment, serum alpha-mannosidase activity in cows and sheep, measured
      by the release of 4-methylumbelliferone from an artificial substrate, was
      markedly decreased to 28 and 40 mumol of 4-methylumbelliferone/L, respectively.
      Mean serum alpha-mannosidase activity of control cows and sheep was 400 +/- 94
      and 422 +/- 42 (mean +/- SD), respectively. In the treated animals, decreased
      serum alpha-mannosidase activities returned to normal or higher activities within
      6 days after treatment was discontinued. Using a jack bean alpha-mannosidase
      assay, increased swainsonine activity (153, 209, and 381 ng/ml, respectively) was
      detected in the serum of cattle and of sheep in the high- and low-dose groups
      within 24 hours after treatment with locoweed. Swainsonine concentration remained
      high, with mean concentrations of 204, 432, and 395 ng/ml (cows and 2 sheep
      groups, respectively) during the treatment period. After treatment, swainsonine
      was rapidly cleared, with estimated serum half-life of 16.4, 17.6, and 20.3 hours
      (cows, and high- and low-dose sheep groups, respectively).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7717576
TI  - Effect of auriculopalpebral nerve block and intravenous administration of
      xylazine on intraocular pressure and corneal thickness in horses.
AB  - Intraocular pressure (IOP) was measured, using applanation tonometry, in both
      eyes of 20 horses after topical application of 0.5% proparacaine to the cornea.
      Ultrasonic pachymetry was used to measure central, mid-peripheral, and peripheral
      corneal thickness (CT) in all 4 quadrants of both eyes of 25 horses. All
      measurements were repeated after auriculopalpebral nerve block, sedation by IV
      administration of xylazine, or combination of nerve block and sedation. Mean IOP
      after topical anesthesia of the cornea was 20.6 +/- 4.7 mm of Hg for the left eye
      and 20.35 +/- 3.7 mm of Hg for the right eye. Mean central CT was 793.2 +/- 42.3
      microns. The peripheral part of the cornea was significantly (P < 0.05) thicker,
      on average, than the central part of the cornea. Auriculopalpebral nerve block
      had no significant effect on IOP or CT. Intravenous administration of xylazine
      resulted in a significant (P < 0.05) decrease in IOP, but had no effect on CT.

PMID- 7717577
TI  - Effects of increasing velocity on braking and propulsion times during force plate
      gait analysis in greyhounds.
AB  - The percentage of limb contact time spent in braking and propulsion was
      determined for the forelimbs and hind limbs of Greyhounds at 2 walk speeds and 3
      trot speeds. Limb contact times decreased significantly (P < 0.05) as velocity
      increased between each velocity range. At a slow walk (0.92 to 1.03 m/s), braking
      and propulsion were 56.1 and 43.6% of contact time in the forelimbs and 41.6 and
      58.1% of contact time in the hind limbs, respectively. At a fast walk (1.06 to
      1.17 m/s), braking and propulsion were 56.7 and 43.5% of contact time in the
      forelimbs and 41.5 and 58.4% of contact time in the hind limbs, respectively.
      There was no significant difference in the percentage of contact time that the
      forelimbs and hind limbs spent in braking and propulsion between the 2 walk
      velocities. At the slow trot (1.5 to 1.8 m/s), braking and propulsion were 56.8
      and 43% of contact time in the forelimbs and 30.1 and 67.6% of contact time in
      the hind limbs, respectively. At the medium trot (2.1 to 2.4 m/s), braking and
      propulsion were 55.9 and 43.5% of contact time in the forelimbs and 33.8 and
      63.2% of contact time in the hind limbs, respectively. At the fast trot (2.7 to
      3.0 m/s), braking and propulsion were 57.2 and 43% of contact time in the
      forelimbs and 37.5 and 61.1% of contact time in the hind limbs, respectively.
      Braking percentage increased and propulsive percentage decreased significantly (P
      < 0.05) in the hind limbs between the slow and fast trot speeds.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7717578
TI  - Determination of carbonic anhydrase III isoenzyme concentration in sera of
      racehorses with exertional rhabdomyolysis.
AB  - The concentration of carbonic anhydrase III isoenzyme (CA-III) in serum samples
      from 216 clinically normal Thoroughbreds was determined by use of an enzyme
      immunoassay. The concentration range of CA-III was from 16.0 to 254.5 ng/ml
      (mean, 56.5 +/- 11.9 ng/ml). Significant differences were not detected according
      to age or sex. To confirm whether serum CA-III concentration was high in horses
      with muscle disease, serum samples of 11 horses with exertional rhabdomyolysis
      were analyzed by enzyme immunoassay. Their serum CA-III concentration was about
      56 times (3,136 +/- 2,610 ng/ml) that of healthy Thoroughbreds. Concentration of
      CA-III was higher in horses with rhabdomyolysis that had been transiently
      recumbent than in horses with mild disease that were reluctant to move. Blood
      samples obtained serially from 6 horses with exertional rhabdomyolysis were
      studied. Serum activities of aldolase, creatine kinase, aspartate transaminase,
      and lactate dehydrogenase were high. Increases and decreases in concentration of
      CA-III were more rapid than that for aldolase, creatine kinase, aspartate
      transaminase, and lactate dehydrogenase activities; thus, CA-III may be
      clinically applicable as a diagnostic marker for muscle disease in horses.

PMID- 7717579
TI  - Characterization of functions of neutrophils from bone marrow of cattle with
      leukocyte adhesion deficiency.
AB  - Marked differences in bone marrow cellularity were observed between cattle
      affected with leukocyte adhesion deficiency (LAD) and control cattle. The number
      of nucleated cells in bone marrow was 2.9 to 8.8 times higher in cattle affected
      with LAD, compared with controls. The myeloid-to-erythroid ratio of bone marrow
      from 3 cattle affected with LAD ranged from 2.4 to 12. Deficient CD18 expression
      on neutrophils isolated from bone marrow of cattle with LAD was clearly detected
      by flow cytometric analysis. Neutrophils from bone marrow of cattle affected with
      LAD appeared round and not flat, after adherence to plastic wells under agarose,
      whereas neutrophils from bone marrow of clinically normal cattle were firmly
      spread on the surface of plastic wells. In the chemotaxis under-agarose assay,
      many pseudopodia were detected on bone marrow neutrophils from clinically normal
      cattle, but were not detected on bone marrow neutrophils from cattle with LAD.
      Activities of chemotactic movements and phagocytosis of neutrophils isolated from
      bone marrow of cattle affected with LAD were documented to be severely impaired.

PMID- 7717580
TI  - Prevalence of Toxoplasma gondii antibodies in sera of hunter-killed white-tailed
      deer in Pennsylvania.
AB  - Serum samples from 593 white-tailed deer in Pennsylvania that were killed by
      hunters in 1991 were examined for Toxoplasma gondii antibodies, by use of the
      modified agglutination test. Sixty percent (357/593) of the deer had T gondii
      antibodies; 10% had titer of 25, 23% had titer of 50, and 27% had titer > or =
      500. Sex-specific differences in prevalence were not detected.

PMID- 7717581
TI  - Diethylcarbamazine-induced Dirofilaria immitis larval death, as indicated by
      immunoglobulin E concentration, in dogs with concurrent Ancylostoma caninum
      infection.
AB  - Immunoglobulin E is produced in response to parasitic nematodes that undergo
      blood and tissue migrations. Results of our previous studies indicated that IgE
      and IgG respond to Dirofilaria immitis in experimentally infected dogs. To
      determine the association between treatment with the larvicide,
      diethylcarbamazine (DEC), and antibody responses and to examine the potential
      influence of infection with a nonfilarid intestinal nematode on isotype-specific
      immune responses, we monitored, by use of isotype-specific ELISA, separate IgE
      and IgG responses against D immitis in 4 groups (A-D) of 8 dogs experimentally
      coinfected with D immitis and Ancylostoma caninum. All dogs were monitored from 2
      weeks before inoculation with D immitis, through postinoculation (PI) week 20.
      Group-B dogs received a daily regimen of 6.6 mg of DEC/kg of body weight. Group-C
      dogs received 4.95 mg of oxibendazole/kg daily. Group-D dogs received DEC and
      oxibendazole, equivalent to the daily doses given to dogs of groups B and C. All
      dogs given oxibendazole had no A caninum at necropsy. Of the groups receiving
      DEC, 3 group-B dogs each had 1 to 2 D immitis at necropsy. When results of
      chronologic IgE determination for all groups were statistically compared, only
      groups B and C had significant (P = 0.0148 and P < 0.00005, respectively)
      increases in IgE values. Group-C dogs had the highest IgE values from PI week 10
      until the end of the study, whereas IgG values were statistically identical to
      those of group-A dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717582
TI  - Effects of vitamin E on immune function of dairy cows.
AB  - The effect of vitamin E supplementation on the immune function of dairy cows was
      studied. Twelve cows were assigned to 1 of the 2 experimental groups: control (no
      vitamin E supplementation), and vitamin E-supplemented. Supplementation of
      vitamin E started 4 weeks before and continued up to 8 weeks after parturition
      and included oral supplementation of vitamin E at the rate of 3,000 IU/cow/d. In
      addition, the same group of cows received 1 injection of vitamin E (5,000 IU), 1
      week prior to the expected date of parturition. Data indicated that blood
      neutrophils isolated from control cows produced twofold less (P < 0.05)
      superoxide anion after parturition, compared with the corresponding value before
      parturition. Furthermore, blood macrophages isolated from control cows produced
      15 and 35% (P < 0.05) less interleukin 1 (IL-1) and major histocompatibility
      (MHC) class-II antigens, respectively, after parturition, compared with the
      corresponding values before parturition. These data, collectively, indicate that
      functions of blood macrophages and neutrophils are depressed during the early
      postpartum period in control cows. In contrast, there were no differences in
      superoxide anion production by blood neutrophils, or in IL-1 production, and MHC
      class-II antigen expression by blood macrophages before and after parturition in
      cows supplemented with vitamin E. There were no differences in lymphocyte
      proliferation, or IL-1 production and MHC class-II antigen expression by mammary
      macrophages when control and vitamin E-supplemented cows were compared. We
      conclude that vitamin E prevented suppression of blood neutrophil and macrophage
      function during the early postpatum period.

PMID- 7717583
TI  - Comparison of argyrophilic nucleolar organizer regions by counting and image
      analysis in canine mammary tumors.
AB  - Two techniques for evaluating argyrophilic nucleolar organizer regions (AgNOR)
      were compared on 74 canine mammary tumors to discriminate between benign and
      malignant lesions. For each lesion, direct counting of AgNOR on at least 100 cell
      nuclei was compared with area, perimeter, and integrated optical density AgNOR
      dot values determined by image analysis. Significant differences between benign
      and malignant tumors were observed with both methods; however, lesions determined
      as aggressive or proliferative by histologic evaluation were only singled out by
      image analysis measurements. Image analysis, in our hands, was a reliable,
      precise, and convenient technique to characterize malignancy in canine mammary
      tumors.

PMID- 7717585
TI  - Effects of medetomidine administration on intracranial pressure and
      cardiovascular variables of isoflurane-anesthetized dogs.
AB  - Intracranial pressure and cardiovascular variables after IV administration of
      medetomidine (0.03 mg/kg of body weight) were evaluated in 6 healthy, mixed-breed
      dogs anesthetized with 1.3% end-tidal isoflurane concentration and mechanically
      ventilated to normocapnia (PaCO2, 35 to 45 mm of Hg). Baseline values were
      determined for intracranial pressure, heart rate, arterial blood pressure,
      cardiac output, mean pulmonary artery pressure, pulmonary capillary wedge
      pressure, central venous pressure, end-tidal CO2 tension and isoflurance
      concentration, arterial pH and CO2 and O2 tensions, and core body temperature.
      Cerebral perfusion pressure, cardiac index, systemic and pulmonary vascular
      resistances, plasma HCO3- concentration, and base excess were calculated.
      Intracranial pressure was measured, using a calibrated, fiberoptic transducer
      placed within the brain parenchyma and secured to the calvarium by means of a
      subarachnoid bolt. Cardiac output was determined by thermodilution. End-tidal CO2
      tension and isoflurane concentration were determined, using an infrared gas
      analyzer. Administration of medetomidine did not change intracranial pressure,
      but was associated with significant (P < 0.05) decreases in values for heart
      rate, cardiac index, end-tidal CO2, and HCO3- and with significant increases in
      systolic, mean, and diastolic pressure; pulmonary artery pressure; systemic
      vascular resistance; central venous pressure; and pulmonary capillary wedge
      pressure.

PMID- 7717584
TI  - Cortical bone concentrations of enrofloxacin in dogs.
AB  - Cortical bone concentrations of enrofloxacin were determined over time in dogs
      after SC administration of the drug. Nineteen healthy adult dogs were
      anesthetized and were given 2.5 or 5.0 mg of enrofloxacin/kg of body weight, SC.
      Serial serum and bone samples were obtained for determination of enrofloxacin
      concentrations at intervals until 8 hours after drug administration. Cortical
      bone samples were procured by surgical disarticulation of successive second
      phalanges. Additional cortical bone samples were taken from long bones in 4 dogs.
      Mean +/- SD peak serum enrofloxacin concentration was 0.54 +/- 0.10 micrograms/ml
      for the 2.5 mg/kg dosage and 0.97 +/- 0.34 micrograms/ml for the 5.0-mg/kg
      dosage. Serum concentration was significantly higher than bone concentration for
      each dosage. Mean peak bone concentrations reached 29% of peak serum values: 0.15
      +/- 0.09 micrograms/g and 0.29 +/- 0.09 micrograms/g for 2.5-mg/kg and 5.0-mg/kg
      dosages, respectively. Serum concentration for the 5.0-mg/kg dosage was
      significantly greater than that for the 2.5-mg/kg dosage for all times, whereas
      bone concentrations for the 5.0-mg/kg dosage were significantly higher at all
      times after 180 minutes. For the duration of the study, cortical bone
      concentrations of enrofloxacin at either dosage exceeded the minimum inhibitory
      concentration (MIC) for the Enterobacteriaceae, but reliably exceeded the MIC for
      Staphylococcus sp only at the 5.0-mg/kg dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717586
TI  - Cannulation of a lateral ventricle in the brain of Holstein calves.
AB  - A surgical technique was developed for implanting a flexible polyurethane cannula
      in a lateral ventricle in the brain of calves. Initially, measurements were made
      on 25 calves at necropsy to develop equations for calculating coordinates for
      cannula placement. The distance (cm) caudal, in the sagittal plane, from the
      coronal suture line to the center of a hole to be drilled in the parietal bone of
      the skull was: 0.73 +/- (0.00925 x body weight [kg]). The distance (cm) lateral
      from the midline to the center of the hole to be drilled was: 0.018 +/- (0.6464 x
      distance caudal). The depth (cm) from the surface of the skull to the dorsal
      surface of the lateral ventricle was: 2.29 + (0.0159 x body weight [kg]). Surgery
      was subsequently performed on 17 calves. A 5-mm-diameter hole was drilled through
      the skull with a hand trephine at coordinates derived from the aforementioned
      regression equations. A polyurethane cannula (total length, 30 cm; 1 mm ID; 2 mm
      OD) covering a stainless-steel 20-gauge blunt-tipped needle (stylet) was lowered
      through the brain and into a lateral ventricle at an angle of 20.5 degrees
      relative to the frontal bones of the skull. The blunt-tipped needle was then
      removed, and CSF was allowed to drip from the cannula to verify placement. One
      stainless-steel screw was inserted 0.6 cm medial, and another was inserted 0.6 cm
      caudal to the hole in the skull. The area around the cannula, bone screws, and
      hole in the skull was covered with dental acrylic (approx 2 cm in diameter) to
      stabilize the cannula.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717587
TI  - Morphologic observation of neutrophil diapedesis across bovine mammary gland
      epithelium in vitro.
AB  - Neutrophils are present in milk of cows as a means of suppressing invading
      pathogens during mastitis. However, the manner by which neutrophils traverse the
      secretory epithelia is still not clear: do they diapedese between epithelial
      cells or do they kill epithelial cells to gain entry into milk? We investigated
      the process of bovine neutrophil diapedesis across bovine mammary gland
      epithelium in vitro. The bovine mammary epithelial cell line MAC-T, grown on
      collagen-coated filters, formed a confluent monolayer with characteristic tight
      junctions, basal-apical polarity, and functional barriers to the dye trypan blue.
      Neutrophils added on the apical surface of the monolayer were stimulated to
      diapedese across the epithelium by the addition of Staphylococcus aureus (10(7)
      colony-forming units/ml) to the basal compartment. Light and transmission
      electron microscopy revealed the series of events for neutrophil transmigration:
      accumulation of neutrophils on the surface of epithelial monolayer; projection of
      pseudopods into intercellular junctions and movement of neutrophils between
      adjacent epithelial cells; and reapproximation of the lateral epithelial cell
      membranes and reformation of the apical tight junctions after neutrophils crossed
      the epithelium. Morphologically, epithelial cell damage caused by neutrophil
      diapedesis was not evident. This in vitro model provides a two-dimensional
      epithelial sheet by which neutrophil diapedesis can be qualitatively studied
      under defined conditions. Results of the study suggest a major mode by which
      bovine neutrophils diapedese across the alveolar epithelia into milk during
      mastitis.

PMID- 7717588
TI  - Right atrial bypass model in the dog.
AB  - In gas exchange studies addressing the storage and transport of CO2 in dogs, a
      model in which cardiac output (QT) can be precisely controlled and measured would
      be beneficial. We identified problems with described extracorporeal circuits and
      implemented right atrial bypass (RAB) in dogs. In 6 anesthetized (chloralose and
      urethane), heparinized dogs (mean +/- SD, 24 +/- 4 kg) with open thorax, cannulas
      were inserted in both vena cavas to drain venous blood return to a reservoir
      (anaerobic bag or bubble oxygenator). A roller pump then drove blood through a
      heat exchanger back to the right atrial appendage. After 1.8 +/- 1.4 hour of RAB,
      physiologic variables remained within reference limits for dogs (QT, 1.5 +/- 0.3
      L/min; blood pressure, 92 +/- 25 mm of Hg; arterial PCO2, 35 +/- 4 mm of Hg; PO2,
      513 +/- 39 mm of Hg; pH, 7.39 +/- 0.08; and tissue CO2 production, 126 +/- 56
      ml/min). To permit study of gas exchange, venous return (and thus, QT) and venous
      PCO2 and PO2 could be accurately regulated and measured over a wide range.
      Maintenance of native pulsatile lung perfusion and cardiogenic oscillations
      minimizes mismatching of pulmonary ventilation and perfusion and facilitates
      studies addressing pulmonary gas exchange. This RAB model is designed so that
      investigators can establish the preparation in a few hours.

PMID- 7717589
TI  - Cardiopulmonary responses in healthy dogs during endoscopic examination of the
      gastrointestinal tract.
AB  - Cardiopulmonary responses were evaluated in 12 dogs undergoing endoscopy
      (gastroscopy and enteroscopy). Constant endoscopic insufflation was used to
      distend the stomach and small intestine for 30 minutes in groups of small (< 10
      kg; n = 4), medium (10 to 20 kg; n = 4), and large (> 20 kg; n = 4) dogs.
      Cardiopulmonary measurements within groups prior to gastric distention
      (preendoscopy) were compared with postendoscopy measurements and with those made
      during endoscopy. After distending the stomach and small intestine, increased
      luminal pressure within the body of the stomach and in the descending duodenum (P
      < 0.05) and increased abdominal girth (P < 0.05) were observed, with the greatest
      changes in small dogs. Caudal vena cava pressures and mean arterial and pulmonary
      artery pressures increased (P < 0.05) during endoscopy. Cardiac index varied,
      with small dogs having greater cardiac index (P < 0.05) during endoscopy,
      compared with that in medium and large dogs. Minute volume remained unchanged
      during insufflation, despite a decrease in tidal volume (P < 0.05), because of an
      increase in respiratory rate (P < 0.05). Arterial blood gas analysis revealed a
      mild, mixed metabolic/respiratory acidosis in all groups. Although
      cardiopulmonary changes associated with gastrointestinal tract endoscopy were
      common, the changes were often small and of little clinical significance.

PMID- 7717590
TI  - Myocardial edema and compromised left ventricular function attributable to
      dirofilariasis and cardiopulmonary bypass in dogs.
AB  - We investigated the relation between left ventricular dysfunction and myocardial
      edema in dogs with heartworm (Dirofilaria immitis) infection that were undergoing
      cardiopulmonary bypass. Dogs with and without D immitis were anesthetized by
      continuous thiopental infusion and were mechanically ventilated. Sonomicrometry
      crystals were placed on the long and short axes of the left ventricle, and a
      Millar pressure transducer was placed in the left ventricular chamber. Pressure
      volume loops were digitized and continuously recorded. Dogs with and without D
      immitis were placed on standard hypothermic cardiopulmonary bypass, with 1 hour
      of aortic cross-clamp. Wet-to-dry weight ratio corrected for residual blood
      volume was used to quantitate the volume of myocardial edema. Preload recruitable
      stroke work was used as a preload-independent index of systolic function. Tau,
      the isovolumic relaxation time constant, was determined to assess diastolic
      relaxation. Dogs with D immitis had increased baseline myocardial wet-to-dry
      weight ratio. After cardiopulmonary bypass, myocardial edema increased in all
      dogs. Acute edema attributable to cardiopulmonary bypass decreased preload
      recruitable stroke work in all dogs of both groups, and dogs with D immitis could
      not be weaned from cardiopulmonary bypass. Myocardial edema increased diastolic
      relaxation times (tau) in dogs with and without D immitis. We conclude that
      cardiopulmonary bypass and heartworm infection induce myocardial edema. This
      edema compromises left ventricular systolic and diastolic function making D
      immitis an important confounding factor in weaning dogs from cardiopulmonary
      bypass.

PMID- 7717591
TI  - Fluid, electrolyte, and packed cell volume shifts in racing greyhounds.
AB  - Arterial blood samples were obtained at rest, just before, and 5 minutes after a
      704-m race, to quantify changes in hematologic variables, plasma electrolyte and
      protein concentrations, osmolality, and acid/base variables. Changes in plasma
      volume were estimated from the change in plasma protein concentration.
      Immediately prior to the race, plasma volume decreased by 10% from rest and total
      circulating RBC volume increased by 60%, attributable to increased RBC number
      rather than size. Increases in blood volume (VB) by 24% and PCV by 29% also were
      detected before the race. Five minutes after the race, plasma volume was 21%
      below the resting value and total circulating RBC volume had increased 73% above
      the resting value, resulting in a 40% increase in PCV. Contraction of the spleen
      appeared responsible for increased PCV and VB before the race and maintenance of
      VB after the race. Plasma chloride concentration was the same before and after
      the race; the chloride content of the plasma decreased by the same fraction (22%)
      as did the plasma volume, indicating Cl- loss from the plasma. Plasma Na+ content
      decreased by a smaller fraction (13%), causing Na+ concentration to increase from
      151 mEq/L at rest to 167 mEq/L after the race. Assuming that Na+ concentration
      was the same throughout the extracellular fluid, H2O likely moved into the
      intracellular compartment. As a consequence of these changes, the inorganic
      strong ion difference in plasma increased by about 16 mEq/L, tending to minimize
      the acid/base disturbance induced by the 33 mEq/L increase in lactate
      concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717592
TI  - Diaphyseal structural properties of equine long bones.
AB  - We evaluated the single-cycle structural properties for axial compression,
      torsion, and 4-point bending with a central load applied to the caudal or lateral
      surface of a diaphyseal segment from the normal adult equine humerus, radius,
      third metacarpal bone, femur, tibia, and third metatarsal bone. Stiffness values
      were determined from load-deformation curves for each bone and test mode.
      Compressive stiffness ranged from a low of 2,690 N/mm for the humerus to a high
      of 5,670 N/mm for the femur. Torsional stiffness ranged from 558 N.m/rad for the
      third metacarpal bone to 2,080 N.m/rad for the femur. Nondestructive 4-point
      bending stiffness ranged from 3,540 N.m/rad for the radius to 11,500 N.m/rad for
      the third metatarsal bone. For the humerus, radius, and tibia, there was no
      significant difference in stiffness between having the central load applied to
      the caudal or lateral surface. For the third metacarpal and metatarsal bones,
      stiffness was significantly (P < 0.05) greater with the central load applied to
      the lateral surface than the palmar or plantar surface. For the femur, bones were
      significantly (P < 0.05) stiffer with the central load applied to the caudal
      surface than the lateral surface. Four-point bending to failure load-deformation
      curves had a bilinear pattern in some instances, consisting of a linear region at
      lower bending moments that corresponded to stiffness values from the
      nondestructive tests and a second linear region at higher bending moments that
      had greater stiffness values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717593
TI  - Effect of deferoxamine and hyperbaric oxygen on free, autogenous, full-thickness
      skin grafts in dogs.
AB  - Free, autogenous, full-thickness skin grafts were applied to 10 dogs; 5 dogs were
      given an iron chelator, deferoxamine-10% hydroxyethyl pentafraction starch (DEF
      HES; 50 mg/kg of body weight, IV), and 5 dogs were given an equal volume of 10%
      hydroxyethyl pentafraction starch (HES) in 0.9% saline solution (5 ml/kg, IV).
      All dogs (DEF-HES/HBO- and HES/HBO-treated) were exposed to 60 minutes of
      hyperbaric oxygen (HBO) at 2 atmospheres absolute pressure twice daily for 10
      days, beginning the day of surgery. The percentage of viable graft on day 10 was
      lower in HES/HBO-treated dogs (mean +/- SD, 13.3 +/- 21.3%; median, 3.0%) than in
      DEF-HES/HBO-treated dogs (64.7 +/- 39.2%; 88.3%; P = 0.095, Mann-Whitney two
      tailed test). There was a positive correlation between percentage of viable graft
      (on day 10) and percentage of haired skin on the graft site (on day 28) for all
      dogs (r = 0.91) and for HES/HBO-treated dogs (r = 0.97). The DEF-HES/HBO-treated
      dogs had less consistent correlation (r = 0.67). Perivascular aggregates of foamy
      cells were observed in the superficial and reticular portions of the dermis and
      in the subcutaneous tissue on both surfaces of the panniculus muscle in the graft
      sites of DEF-HES/HBO-treated dogs. These cells were also observed in the dermis,
      but not subcutaneous tissue of the control skin sections, and in some viscera of
      DEF-HES/HBO-treated dogs. Deferoxamine appears to attenuate the detrimental
      effect of HBO and HES on survival of free skin grafts.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7717594
TI  - Comparison of the holding power of 3.5-mm cortical versus 4.0-mm cancellous
      orthopedic screws in the pelvis of immature dogs (cadavers).
AB  - A 3.5-mm cortical orthopedic screw was compared with a 4.0-mm cancellous screw
      for maximal load to failure in the pelvis of immature dogs. The pelvis from young
      cadavers (7 to 13 months old) was divided into hemipelves and used for testing of
      the 2 screw types. Two sites in each hemipelvis were used, mid-shaft of the ilium
      and mid-sacrum, including the wing of the ilium. The screws were extracted, and
      maximal load to failure and mode of failure were recorded. Maximal load to
      failure per millimeter of engaged thread was calculated. In either pelvic site,
      the 4.0-mm cancellous screw required a significantly (P < 0.05) higher pullout
      force per millimeter of engaged screw threads than did the 3.5-mm cortical bone
      screw.

PMID- 7717595
TI  - Contribution of external forces to left ventricular diastolic pressure.
      Implications for the clinical use of the Starling law.
AB  - OBJECTIVE: To test whether a substantial proportion of measured resting left
      ventricular diastolic pressure stems from forces external to the left ventricle
      (such as right-heart filling) in normal and chronically diseased hearts. DESIGN:
      Nonrandomized study with single intervention. SETTING: University hospital.
      PATIENTS: 29 patients referred for cardiac catheterization who had normal left
      ventricles and ejection fractions (n = 12); chronic heart disease due to
      idiopathic dilated cardiomyopathy (n = 6); ischemic heart disease (n = 6); or
      left ventricular hypertrophy (n = 5). INTERVENTION: Acute reduction of external
      forces imposed on the left ventricle using balloon obstruction of inferior vena
      caval inflow to the right heart. MEASUREMENTS: Continuous catheter-derived left
      ventricular pressure-volume data before and after abrupt obstruction of inferior
      vena caval inflow. Diastolic pressures were measured at the same volume just
      before atrial systole before and after sudden decrease of external (right-heart
      and pericardial) forces. The resulting decline in pressure was a measure of the
      contribution of these external forces to resting left ventricular diastolic
      pressure. RESULTS: The decline in pressure when external forces were released
      averaged -19% +/- 13% with minimal change in left ventricular end-diastolic
      volume (-3.66% +/- 6.7%) and cardiac output (-5% +/- 8%). In all patients
      combined, the decline in pressure when external forces (delta Pd) were released
      correlated with resting left ventricular diastolic pressure (LVPd) given by:
      delta Pd = 0.38 x (LVPd-6) [r = 0.86, P < 0.0001]. This indicates that when
      resting diastolic pressure was more than 6 mm Hg, almost 38% of the pressure was
      due to external factors. This percentage was similar among all subgroups.
      Furthermore, the left ventricular diastolic pressure could be reduced by this
      percentage with only minimal compromise to ventricular filling and cardiac
      output. CONCLUSIONS: A substantial proportion of measured resting left
      ventricular diastolic pressure stems from forces extrinsic to the left ventricle
      rather than from diastolic stiffness in the left ventricle itself. This markedly
      influences the dependence of cardiac output on filling pressure and has important
      implications for clinical application of the Starling law.

PMID- 7717596
TI  - The safety and diagnostic accuracy of minibronchoalveolar lavage in patients with
      suspected ventilator-associated pneumonia.
AB  - OBJECTIVES: To assess the safety of minibronchoalveolar lavage done by
      respiratory therapists for the evaluation of suspected ventilator-associated
      pneumonia and to determine the diagnostic agreement between quantitative lower
      airway cultures obtained by the minibronchoalveolar lavage and protected specimen
      brush techniques. DESIGN: A prospective direct comparison of two diagnostic
      techniques. SETTING: An academic tertiary care center in St. Louis, Missouri.
      PATIENTS: 72 consecutive patients suspected of having ventilator-associated
      pneumonia on the basis of clinical evidence. INTERVENTIONS: Sampling of lower
      airway secretions using the protected specimen brush and minibronchoalveolar
      lavage techniques. MAIN OUTCOME MEASURES: Clinical complications and quantitative
      cultures of respiratory secretions. RESULTS: 72 patients suspected of having
      ventilator-associated pneumonia (first episode) were evaluated using
      minibronchoalveolar lavage. In 42 patients, lower airway secretions were also
      obtained using the protected specimen brush technique. No change in arterial
      blood oxygen saturation or heart rate occurred after minibronchoalveolar lavage
      (P > 0.2). Mean arterial pressure slightly increased with minibronchoalveolar
      lavage (baseline mean pressure, 90.1 mm Hg [CI, 88.4 to 91.7 mm Hg]; average
      within-person change, 2.6 mm Hg; P = 0.024). Good diagnostic agreement was shown
      for quantitative cultures obtained with the protected specimen brush and
      minibronchoalveolar lavage techniques (kappa statistic, 0.63; concordance,
      83.3%); 10(3) colony forming units/mL was used as the threshold for a clinically
      significant culture result. CONCLUSIONS: Minibronchoalveolar lavage is a safe and
      technically simple procedure for obtaining quantitative lower airway cultures in
      patients requiring mechanical ventilation. Quantitative culture results obtained
      by minibronchoalveolar lavage are similar to those obtained by the protected
      specimen brush technique.

PMID- 7717597
TI  - Does eradicating bacteriuria affect the severity of chronic urinary incontinence
      in nursing home residents?
AB  - OBJECTIVE: To determine the effects of eradicating otherwise asymptomatic
      bacteriuria on the severity of chronic urinary incontinence among nursing home
      residents. DESIGN: Residents were categorized as nonbacteriuric or bacteriuric on
      the basis of urine cultures. Bacteriuric residents were then randomly assigned to
      immediate and delayed treatment groups. The delayed treatment group was included
      to control for spontaneous changes in the severity of incontinence. The immediate
      treatment group received antimicrobial therapy for 7 days; after outcome measures
      had been repeated, the delayed treatment group was treated. SETTING: 6 community
      based nursing homes. PATIENTS: Nursing home residents with chronic urinary
      incontinence. MEASUREMENTS: The frequency and volume of urinary incontinence were
      determined by physical checks for wetness by trained research aides hourly
      between 7 a.m. and 7 p.m. for 3 days in all patient groups (non-bacteriuric,
      bacteriuric with immediate treatment, and bacteriuric with delayed treatment) at
      baseline, after the immediate treatment group was treated, and again after the
      delayed treatment group was treated. RESULTS: 191 residents were enrolled, and
      176 completed the study. Bacteriuria was eradicated by antimicrobial therapy in
      71 residents (40%), and 17 residents (10%) had bacteriuria before and after
      therapy. The percentage of hourly checks at which the residents were found wet
      and other measures of incontinence severity remained essentially the same after
      bacteriuria was eradicated. In the nonbacteriuric group, the percentage of checks
      that were wet increased from 29% (95% CI, 26% to 32%) at baseline to 30% (CI, 27%
      to 34%) on repeated measurement. In the bacteriuric groups, the percentage
      increased from 34% (CI, 30% to 38%) before treatment to 35% (CI, 31% to 39%)
      after bacteriuria was eradicated. The presence of pyuria did not affect the
      results. CONCLUSION: Eradicating bacteriuria has no short-term effects on the
      severity of chronic urinary incontinence among nursing home residents. Our data
      support the practice of not treating asymptomatic bacteriuria in this population
      and validate the recommendations in the Health Care Financing Administration's
      Resident Assessment Protocol for urinary incontinence.

PMID- 7717598
TI  - Intermittent trimethoprim-sulfamethoxazole compared with dapsone-pyrimethamine
      for the simultaneous primary prophylaxis of Pneumocystis pneumonia and
      toxoplasmosis in patients infected with HIV.
AB  - OBJECTIVE: To evaluate the efficacy and safety of two oral, intermittent drug
      regimens for the simultaneous primary prophylaxis of Pneumocystis carinii
      pneumonia and toxoplasmosis in patients with HIV infection. DESIGN: Nonblinded
      randomized study: Patients received either 1) trimethoprim-sulfamethoxazole (160
      mg-800 mg orally twice a day on a thrice weekly regimen) or 2) 100 mg of dapsone
      plus 50 mg of pyrimethamine orally twice weekly. SETTING: University teaching
      hospital in Barcelona. PATIENTS: 230 patients infected with HIV who had CD4 cell
      counts of less than 200 x 10(6)/L and who had not previously had P. carinii
      pneumonia or toxoplasmosis. MEASUREMENTS: Clinical and biological evaluations;
      adverse reactions; and end points of P. carinii pneumonia, toxoplasmosis, and
      death. RESULTS: After a median follow-up of 430 days, 6 (6.3%) of 96 evaluable
      patients receiving dapsone-pyrimethamine and 0 of 104 evaluable patients
      receiving trimethoprim-sulfamethoxazole developed P. carinii pneumonia (P <
      0.0001). The cumulative rates of P. carinii pneumonia at 12 and 24 months were 0%
      and 0% for patients receiving trimethoprim-sulfamethoxazole and 4% and 11% for
      patients receiving dapsone-pyrimethamine (Mantel-Cox, P = 0.014). However, only
      one episode of P. carinii pneumonia developed while patients were taking these
      drugs. No differences were observed for toxoplasmosis (one episode in the
      trimethoprim-sulfamethoxazole arm and two in the dapsone-pyrimethamine arm), with
      cumulative rates at 12 and 24 months of 0% and 4% for the trimethoprim
      sulfamethoxazole arm and 2% and 7% for the dapsone-pyrimethamine arm (P = 0.65).
      Similar mortality rates were observed during follow-up (P = 0.85). Nineteen
      patients (9.5%) discontinued therapy with the drugs because of adverse effects:
      Ten were in the trimethoprim-sulfamethoxazole arm and 9 were in the dapsone
      pyrimethamine arm (P = 0.95). CONCLUSIONS: Thrice-weekly trimethoprim
      sulfamethoxazole is an effective and well-tolerated regimen for the simultaneous
      primary prophylaxis of P. carinii pneumonia and toxoplasmosis in patients
      infected with HIV. Twice-weekly dapsone-pyrimethamine appears to be a safe and
      effective alternative.

PMID- 7717599
TI  - Eradication of Helicobacter pylori infection in primary low-grade gastric
      lymphoma of mucosa-associated lymphoid tissue.
AB  - OBJECTIVE: To determine the effect of eradicating Helicobacter pylori infection
      on the course of low-grade gastric mucosa-associated lymphoid tissue (MALT)
      lymphoma. DESIGN: Prospective cohort study. SETTING: University internal medicine
      clinics, a referral oncology center in southern Switzerland, and a
      gastroenterology referral center in northern Italy. PATIENTS: 26 patients with
      localized primary low-grade gastric MALT lymphoma. INTERVENTION: Treatment for H.
      pylori infection (bismuth or omeprazole or both, amoxicillin, and metronidazole
      for 14 days). MAIN OUTCOME MEASURES: Endoscopic biopsy specimens of the gastric
      mucosa were obtained every 3 to 6 months after treatment for H. pylori infection.
      RESULTS: Helicobacter pylori was completely eradicated in 25 of 26 patients, but
      4 patients needed second-line antibiotic treatment to eradicate the
      microorganism. Disappearance or almost total regression of the lymphomatous
      tissue was observed in 15 of the 25 evaluable patients (60%; CI, 39% to 79%);
      however, disappearance or almost total regression was evident in the first biopsy
      specimen after treatment for H. pylori infection in only 8 of the 15 patients.
      CONCLUSIONS: Our study confirms recent anecdotal reports of regression of gastric
      MALT lymphoma after eradication of H. pylori and indicates that the growth of
      these extranodal lymphomas may depend on H. pylori.

PMID- 7717600
TI  - Implantable cardioverter-defibrillators: implications for the
      nonelectrophysiologist.
AB  - PURPOSE: To review clinical scenarios in which nonelectrophysiologist physicians
      may interact with patients who have implantable defibrillators. DATA SOURCES:
      Peer-reviewed original articles and reviews addressing aspects of implantable
      defibrillator therapy that are relevant to the clinician. DATA SYNTHESIS: The
      capacity of implantable defibrillators to recognize and treat tachyarrhythmias
      can be temporarily disabled by placing a magnet on top of all devices. General
      surgery, radiotherapy, lithotripsy, and electroconvulsive therapy can usually be
      safely done under continuous electrocardiographic monitoring in patients with
      implantable defibrillators. The device should be deactivated before the procedure
      is done and reactivated and reassessed immediately afterward. Magnetic resonance
      imaging is usually contraindicated in patients wit implantable defibrillators.
      The presence of an implantable defibrillator should not deter standard
      resuscitation techniques. Multiple defibrillator discharges in a short period of
      time represent a serious problem. Causes of multiple discharges include
      ventricular electric storm, inefficient defibrillation, nonsustained ventricular
      tachycardia, and inappropriate shocks caused by supraventricular tachyarrhythmias
      or oversensing of signals. These patients should be initially evaluated in a
      setting that allows electrocardiographic monitoring and cardiac resuscitation.
      The defibrillator should be deactivated if inappropriate firing is documented.
      Infections of implantable defibrillator systems are potentially life-threatening,
      and empiric oral antibiotic therapy should never be given when this possibility
      exists. Adjustment disorders specific to the defibrillator, including anxiety
      with secondary panic reaction; defibrillator dependence, abuse, or withdrawal;
      and imaginary shocks are not uncommon. CONCLUSIONS: Defibrillator therapy has
      become increasingly popular and complex. A basic understanding of these devices
      and skills in the short-term management of device-related problems is valuable
      for most physicians. These management guidelines will facilitate delivery of
      optimal care when specialized staff and material resources are not available.

PMID- 7717601
TI  - Diethylstilbestrol revisited: a review of the long-term health effects.
AB  - PURPOSE: To review the literature on the long-term health effects of exposure to
      diethylstilbestrol (DES) among women prescribed DES during pregnancy (DES
      mothers), among their children exposed inutero to the drug (DES sons and
      daughters) and among the progeny of these exposed sons and daughters (DES
      grandchildren). DATA SOURCES: English-language articles were identified through
      MEDLINE and CANCERLIT searches and through review of the bibliographies of
      identified articles. STUDY SELECTION: All human studies relevant to long-term
      health effects of exposure to DES were reviewed. DATA EXTRACTION: Descriptive
      data on existing DES cohorts were extracted from early publications. Risk
      estimates for health effects were extracted from published reports. DATA
      SYNTHESIS: An estimated 5 to 10 million Americans received DES during pregnancy
      or were exposed to the drug in utero. Exposure to DES has been associated with an
      increased risk for breast cancer in DES mothers (relative risk, < 2.0) and with a
      lifetime risk of clear-cell cervicovaginal cancer in DES daughters of 1/1000 to
      1/10,000. The association between DES exposure and testicular cancer in DES sons
      remains controversial. Exposure to DES has also been linked to reproductive tract
      abnormalities in DES sons and daughters that consist of immune system disorders
      and psychosexual effects. No evidence for transgenerational effects currently
      exists. Recommendations for screening persons exposed to DES are reviewed.
      CONCLUSIONS: Further research is needed to define long-term health effects
      related to DES exposure. Such research would provide a basis for counseling
      persons exposed to DES and would further understanding of environmental and
      pharmacologic compounds similar to DES.

PMID- 7717602
TI  - A leading medical school seriously damaged: Vienna 1938.
AB  - Misguided by the notion that the decline of the German race would be prevented by
      purifying "Aryan blood" and eliminating foreign, particularly Jewish, influences,
      the Nazis evicted all Jews from universities within their growing empire during
      the Third Reich. The Medical Faculty of Vienna suffered more than any other
      European faculty from "race hygiene." Within weeks of the Nazi annexation of
      Austria in 1938, 153 of the Faculty's 197 members were dismissed. By far the most
      frequent reason for dismissal was Jewish origin. Most victims managed to
      emigrate, many died in concentration camps, and others committed suicide. The
      "cleansing" process encountered little resistance, and the vacant posts were
      quickly filled with persons known not for their medical expertise but for their
      political trustworthiness. It was in this climate that medical atrocities could
      be committed. After the collapse of the Third Reich, most members of the Faculty
      were burdened with a Nazi past. Most remained in office, and those who had to
      leave were reinstituted swiftly. The Jews evicted in 1938 were discouraged from
      returning. These events have significantly--and with long-lasting effects-
      damaged the quality of a once-leading medical school. This story needs to be told
      to honor its victims and to fortify us so that history does not repeat itself.

PMID- 7717603
TI  - Medicine and the Holocaust: learning more of the lessons.

PMID- 7717604
TI  - Straight talk about rationing.

PMID- 7717605
TI  - The privilege and the pain.

PMID- 7717606
TI  - Increased resting metabolic rate in congestive heart failure.

PMID- 7717607
TI  - Diagnosis and treatment of primary aldosteronism.

PMID- 7717608
TI  - Bone density and body weight in hyperparathyroidism.

PMID- 7717609
TI  - Dapsone in thrombocytopenia of the antiphospholipid antibody syndrome.

PMID- 7717610
TI  - Possible transmission of hepatitis C virus infection with intravenous
      immunoglobulin.

PMID- 7717611
TI  - Hepatotoxicity caused by metronidazole overdose.

PMID- 7717612
TI  - Pemphigus of the larynx and esophagus.

PMID- 7717613
TI  - Subspecialty work force issues.

PMID- 7717614
TI  - On esophagoscopy and sword-swallowing. 1969.

PMID- 7717615
TI  - Endoscopic vocal fold microflap: a three-year experience.
AB  - Surgical techniques for the removal of vocal fold (VF) disorders that arise
      within the lamina propria must permit the preservation and/or restoration of VF
      vibratory characteristics. The endoscopic VF microflap is designed to do such. A
      retrospective study was undertaken to evaluate the efficacy of this procedure.
      Forty microflaps (7 bilateral, 1 revision) were performed on 32 patients. Charts
      and surgical pathology findings were reviewed. Preoperative and 3-month
      postoperative video recorded voice samples and stroboscopic examination results
      were compared. Findings on perceptual voice analysis did not significantly
      change. Stroboscopic examinations revealed improved postoperative VF closure in
      27 of 29 patients with impaired preoperative closure and return of mucosal wave
      in 18 of 24 VFs operated on for the excision of cysts or polyps. When present
      preoperatively (6 patients), the mucosal wave was preserved. Most patients (28 of
      30) rated themselves as clinically improved. The endoscopic VF microflap is
      efficacious in the treatment of selected VF disorders. The surgical technique is
      discussed.

PMID- 7717616
TI  - Positron emission tomography in the evaluation of laryngeal carcinoma.
AB  - Positron emission tomography (PET) is a relatively new radiologic imaging
      technique based on glucose analog uptake and metabolism in tumor tissue. In this
      study, PET was used in evaluating 38 patients with laryngeal cancer. Twenty-five
      patients were examined with PET prior to treatment to study the reliability of
      PET in identifying the primary tumor and assessing regional nodal status; 13
      patients who had previously received irradiation with curative intent and who
      represented differential diagnostic problems were imaged to differentiate between
      irradiation effects and recurrent or residual cancer. Findings for both groups
      were compared to results of clinical evaluation and those of computed tomography
      (CT) and magnetic resonance imaging (MRI). The PET results were essentially
      identical to those of CT, MRI, and clinical evaluation in identifying metastatic
      lesions (82% correct), and were as reliable as CT and MRI for correctly
      identifying primary tumors (88%). Positron emission tomography was most helpful
      in differentiating recurrent tumor from postirradiation tissue sequelae. However,
      its lack of anatomic detail made PET less valuable for primary staging and
      therapeutic planning. It may enhance the diagnostic accuracy of CT and MRI where
      anatomic distortions occur or where diagnostic criteria for CT and MRI are
      ambiguous.

PMID- 7717617
TI  - Tracheoesophageal puncture in irradiated patients.
AB  - Tracheoesophageal puncture (TEP) with use of a voice prosthesis is widely
      accepted as an excellent method of postlaryngectomy vocal rehabilitation. Many
      patients with advanced cancer require postoperative radiotherapy (RT), while
      other cancer patients have been treated with RT as a primary treatment and come
      to laryngectomy for salvage. The influence of RT on outcome of the TEP procedure
      with respect to successful speech and potential complications has not been widely
      discussed. We retrospectively reviewed 77 consecutive cases of TEP in patients
      who had received RT and laryngectomy for laryngeal cancer. All cases had a
      minimum of 6 months of follow-up. All 77 patients were successful in obtaining
      speech with the TEP, and 75 (97%) continued to be TEP users thereafter. Eight
      patients (10%) developed complications in the course of treatment. There was no
      mortality. In selected patients, TEP after RT is a relatively safe and effective
      method of vocal rehabilitation.

PMID- 7717618
TI  - Trade-off between airway resistance and optical resolution in pediatric rigid
      bronchoscopy.
AB  - Contemporary pediatric rigid bronchoscopy reflects the culmination of years of
      work by prominent endoscopists aided by technical developments in optical physics
      and refinements in optical lens manufacturing. Improved neonatal and pediatric
      care has allowed survival of premature infants, many with bronchopulmonary
      diseases. Rigid bronchoscopy in these infants is demanding and has necessitated
      the development of miniaturized telescopic bronchoscopes. This study documents
      airway pressures through bronchoscopes with and without endoscopic telescopes,
      analyzes and quantitates optical resolution, discusses the trade-offs between
      these instruments in airway resistance and optical resolution, and makes
      recommendations regarding which combinations of endoscopes and bronchoscopes
      provide the best resistance and resolution profiles. We conclude that the size
      1.9-mm endoscopic telescope provides the most favorable resistance and resolution
      profile for the size 2.5 to 3.0 bronchoscopes, the 2.8-mm telescope is ideal for
      the 3.5 bronchoscope, and the 4.0-mm telescope works best with the 4.0 and larger
      bronchoscopes. Furthermore, optical forceps and side-channel forceps used during
      bronchial foreign body removal cause little change in airway resistance.

PMID- 7717619
TI  - Intracranial complications of sinusitis in childhood.
AB  - Complications of sinusitis in children, such as intracranial abscess formation,
      are uncommon and are often clinically unremarkable in comparison to similar
      disease processes in adults. Between 1983 and 1991, 443 children were admitted to
      Children's National Medical Center in Washington, DC, for treatment of sinusitis.
      Fourteen of these children presented with intracranial extension of the infection
      and abscess formation. A retrospective review of these patients revealed that the
      risk of developing an intracranial abscess secondary to sinusitis was 3%. The
      management of these patients included surgical drainage of the infected sinuses
      and intracranial surgical exploration. Cranialization and exenteration of the
      frontal sinus proved to be effective single-stage procedures. While not indicated
      in all patients, these procedures eliminated the sinus as a source of continued
      or potential infection and obviated the need for a second obliterative procedure.
      Combined antimicrobial therapy and surgical drainage should be the management
      protocol.

PMID- 7717620
TI  - Vocal cord palsy: possible late complication of radiotherapy for head and neck
      cancer.
AB  - Cranial nerve palsies are uncommon complications of radiotherapy for head and
      neck cancer. A review of the literature reveals that cranial nerve damage after
      radiotherapy has been reported for the optic, oculomotor, trigeminal, abducens,
      cochlear, vagus, spinal accessory, and hypoglossal nerves. The hypoglossal nerve
      appears to be the most commonly affected, and the recurrent laryngeal nerve is
      seldom involved. The case histories of three patients who developed vocal cord
      palsy from 21 to 34 years after a course of curative or postoperative
      radiotherapy for carcinoma of the head and neck are presented. Two patients had
      bilateral palsy, and in the third patient, bilateral damage cannot be excluded.
      Physical examination and radiographic investigations on admission and on follow
      up did not demonstrate any evidence of tumor recurrence, cervical or distant
      metastases, or second primary tumors. The distinction between irradiation-induced
      palsy and that due to malignancies is emphasized.

PMID- 7717621
TI  - Otoacoustic emission measurements in evaluation of the immediate effect of
      ventilation tube insertion in children.
AB  - It is generally acknowledged that hearing assessment is needed before and after
      possible surgical intervention in children with otitis media with effusion. The
      conventional method in young children is visual reinforcement audiometry, which
      requires much time and cooperation from the child. The assessment of otoacoustic
      emissions may be an alternative, as it is proven to be rapid, easy, and objective
      as a screening procedure. We studied the applicability of click-evoked
      otoacoustic emissions to assess hearing acuity in children with otitis media with
      effusion who were scheduled for ventilation tube insertion. To avoid cooperation
      problems, the measurements were performed in the operating room immediately
      before and after ventilation tube insertion with the child under general
      anesthesia. None of the ears tested (n = 29) showed any increase in otoacoustic
      emissions when preoperative and postoperative levels were compared. At follow-up
      visits, however, 80% of the tested ears did. The acute outcome may be best
      explained by assuming that the surgical manipulations themselves were
      responsible, either through their fatiguing effects on the outer hair cells
      caused by the suctioning noise, or through their mechanical effects on the middle
      ear processes that govern reverse transmission from the cochlea to the outer ear
      canal. We conclude that it is not worthwhile to measure otoacoustic emissions
      directly after ventilation tube insertion to assess the effect on hearing acuity,
      although they may be valuable in the outpatient setting.

PMID- 7717622
TI  - Sutton's disease (periadenitis mucosa necrotica recurrens).
AB  - Sutton's disease is characterized by giant necrotizing ulcers around minor
      salivary glands and is of unknown cause. We report a case, review the medical
      literature, and discuss the treatment of this affliction.

PMID- 7717623
TI  - Nonnasopharyngeal lymphoepitheliomas (undifferentiated carcinomas) of the upper
      aerodigestive tract.
AB  - Lymphoepitheliomas are malignant tumors of epithelial origin with various amounts
      of reactive lymphocytic infiltrate. Although initially described in the
      nasopharynx (World Health Organization type 3 nasopharyngeal carcinoma), these
      tumors have been identified in various locations throughout the body. A strong
      association with Epstein-Barr virus (EBV) infection has been established for the
      nasopharyngeal type. Outside the nasopharynx, lymphoepitheliomas are exceedingly
      rare in the upper aerodigestive tract, with only isolated case reports of tumors
      in the larynx, trachea, and hypopharynx. This article features a rare case of
      lymphoepithelioma of the pyriform sinus. Furthermore, serologic testing, as well
      as in situ tumor DNA amplification (using the polymerase chain reaction) and
      hybridization techniques, demonstrated an association of this lesion with EBV
      infection. The characteristic histopathologic features common to this disease
      entity are presented, and the literature is reviewed with regard to
      lymphoepitheliomas of the upper aerodigestive tract outside the nasopharynx.
      Association of lymphoepitheliomas with EBV infection will be discussed.

PMID- 7717624
TI  - Measurements of the stapes superstructure.
AB  - Ten human stapes from fresh temporal bones were measured to obtain relevant
      distances of the stapes superstructure. The dimensions of the parts of the
      superstructure are as follows: 1) stapes head 1.14 mm (range, 0.91 to 1.49) in
      diameter parallel to the axis of the footplate and 0.83 mm (range, 0.65 to 1.08)
      perpendicular to it; 2) stapes head to shoulders 0.93 mm (range, 0.81 to 1.07),
      head to foramen 1.26 mm (range, 1.15 to 1.39), and head to lateral surface of
      stapes footplate 3.19 mm (range, 2.91 to 3.45); 3) neck width parallel to the
      axis of the footplate 1.18 mm (range, 0.88 to 1.47) and 0.64 mm (range, 0.48 to
      0.88) perpendicular to it; 4) anterior crus 0.58 mm wide (range, 0.41 to 0.74) at
      the shoulder of the arch and 0.51 mm (range, 0.39 to 0.65) closer to the stapes
      footplate; 5) posterior crus 0.65 mm wide (range, 0.46 to 0.77) at the shoulder
      of the arch and 0.55 mm (range, 0.38 to 0.75) closer to the stapes footplate; and
      6) maximum width of entire superstructure near footplate 2.48 mm (range, 2.06 to
      2.98).

PMID- 7717625
TI  - Nasotracheal airway-oropharyngeal alimentary canal: a microvascular technique for
      reconstruction of the upper airway after total laryngectomy.
AB  - Every patient who has to be laryngectomized because of a carcinoma is concerned
      with the loss of his or her voice and the presence of a permanent tracheostoma in
      his or her neck. While various methods for producing a substitute voice are
      available (esophageal voice, voice devices, voice-shunt operations with or
      without voice prosthesis), it is usually impossible after laryngectomy to
      reconstruct a complete upper airway so that the tracheostoma can be closed. One
      potential method for reconstruction of the airway is its division into a
      nasotracheal airway and an oropharyngeal alimentary canal. Ten Alsatian dogs were
      laryngectomized, and a microvascularly anastomosed jejunal autograft was inserted
      as a junction between the tracheal stump and the circularly exposed nasopharynx,
      while the pharynx was reconstructed separately. One week postoperatively, oral
      feeding could be started again; at the same time breathing was possible via the
      reconstructed nasotracheal airway, which was kept open by insertion of a silicone
      tube. By means of this microvascular technique, a complete nasal airway could be
      reconstructed surgically after laryngectomy.

PMID- 7717626
TI  - Ultrasonographic imaging of sternocleidomastoid tumor of infancy.

PMID- 7717627
TI  - Pneumocephalus as a complication of intranasal ethmoidectomy and polypectomy.

PMID- 7717628
TI  - "Inflammatory pseudotumor": what is it? How does it behave?
AB  - Inflammatory pseudotumor, as a histologic diagnosis and carrying with it the
      prospect of a benign clinical course, is rather firmly entrenched as a pulmonary
      lesion. Extrapulmonic forms, however, are farraginous and, as reported, have
      included lesions having few, or even none, of the histologic features of those in
      the lungs. For those more closely aligned with the fibroblastic or
      myofibroblastic phase of the lung lesions, their biologic behavior can belie
      their histology in that they can be locally aggressive and metastasize as
      sarcomas. For those tumors in the upper airway, and especially in the abdomen,
      pathologists should be very circumspect in the use of inflammatory pseudotumor as
      a diagnosis, and clinicians should not be lulled into denying the extrapulmonic
      forms their due respect.

PMID- 7717629
TI  - Predictors of postoperative performance with cochlear implants.
AB  - One objective of the Department of Veterans Affairs study: A Prospective
      Randomized Study of Advanced Cochlear Implants was to attempt to identify
      preoperative patient characteristics that might predict postoperative
      performance. We studied the relationship between all preoperative factors and the
      2-year postoperative performance on 24 audiological tests for 82 patients who
      were implanted with the Ineraid, Nucleus, or 3M/Vienna device. Results of the
      univariate analysis indicated that computed tomographic findings of the cochlea
      and round window, IQ, age at implantation, length of deafness, profound deafness,
      and lipreading ability weakly correlated to postoperative performance. The
      multivariate analysis showed age at time of implantation, IQ, and lipreading
      ability to be predictive of postoperative performance.

PMID- 7717630
TI  - Performance as a function of time: a study of three cochlear implant devices.
AB  - This study examines the relationship of time to cochlear implant patient
      performance and the effect of device design on patient performance over time.
      Data were collected for patients who were implanted with Nucleus 22, Smith &
      Nephew Richards Ineraid, or 3M/Vienna cochlear implants as part of the Veterans
      Administration study on cochlear implants. Patients were administered a
      comprehensive audiological test battery prior to implantation, at stimulation,
      and 3 months, 1 year, and 2 years poststimulation. Results show that patient
      performance improved over the course of the study, with performance levels with
      each multichannel implant being similar at the study end point. The Nucleus
      device produced maximum performance sooner than the Ineraid device did, and
      performance of the single-channel 3M was consistently below that of the
      multichannel devices.

PMID- 7717631
TI  - Tinnitus in the profoundly hearing-impaired and the effects of cochlear implants.
AB  - Of the 82 adult patients implanted in the Department of Veterans Affairs
      Cooperative Studies Program 304, 22 patients (27%) reported a bothersome tinnitus
      preoperatively. The tinnitus handicap experienced preoperatively in this
      profoundly deaf population is greater than that reported by mildly to severely
      hearing-impaired patients. The magnitude of their handicap was not correlated
      with age or preoperative hearing loss. After 2 years of cochlear implant use, a
      reduction in the tinnitus handicap was reported in 9, and an increase was noted
      in 3 of the 22 patients. In addition, 3 patients experienced a "severe" tinnitus
      2 years after receiving a cochlear implant, whereas they had not reported a
      "bothersome" tinnitus preoperatively. One patient reported a tinnitus immediately
      after the surgery, but it subsided within a few days.

PMID- 7717633
TI  - Multicenter comparative study of cochlear implants: surgical results.
AB  - Cochlear implant surgery by a group of experienced surgeons proceeded without
      major complications. Computed tomography scans tended to underestimate cochlear
      obstruction, but a drill-out was infrequently required if the scan was apparently
      normal.

PMID- 7717634
TI  - Influence of processing strategies on cochlear implant performance.
AB  - The development of new processing strategies has allowed for the improvement of
      auditory skills in cochlear implant recipients. This study examines the effects
      of a change in processing strategy on the individual recipients of the Nucleus
      cochlear prosthesis. Twenty-five subjects who had used the F0F1F2 processing
      strategy (WSP III) for 2 years were switched to the MPeak strategy (MSP) and
      retested immediately and after 3 months. Results revealed an improvement in
      speech recognition ability with the MPeak strategy in those subjects who were
      able to perceive speech with the F0F1F2 processing strategy.

PMID- 7717632
TI  - Change in the quality of life of adult cochlear implant patients.
AB  - Changes in the quality of life perceived by patients over a 24-month period were
      examined by means of three questionnaires: the Patient Quality of Life Form, the
      Index Relative Questionnaire Form, and the Performance Inventory for Profound
      Hearing Loss Answer Form. In addition, the relationships among the three
      questionnaires were examined as a function of age, length of deafness, and a
      battery of selected audiological tests. The results of the study indicate that a
      cochlear implant makes significant, positive changes in the quality of life of
      patients and in their ability to communicate. The patients and their relatives
      differ somewhat in their perceptions of these changes. The degree of improvement
      in quality of life perceived by a patient as the result of an implant is a
      function of the years of deafness. In general, the longer an individual has been
      deaf, the less improvement in quality of life that is perceived.

PMID- 7717635
TI  - Research during higher surgical training: a luxury or a must?

PMID- 7717636
TI  - Pyogenic hepatic abscess after pancreatic resection for chronic pancreatitis.
AB  - Seventeen patients underwent surgery for alcohol-induced chronic pancreatitis.
      Three patients later presented with pyogenic liver abscess. The time interval
      between surgery and presentation with hepatic abscess varied from 6 weeks to 3.5
      years. All patients were diabetic, the presentation was insidious and all made an
      uneventful recovery, two with percutaneous drainage and one with antibiotics
      alone. The aetiology of this uncommon complication is discussed.

PMID- 7717637
TI  - Surgical management of the septic complications of diverticular disease.
AB  - This retrospective study has reviewed the surgical management of the septic
      complications of diverticular disease involving the left colon in 77 patients who
      presented between 1980 and 1992. Over this period, Hartmann's resection continued
      to be the predominant surgical procedure. The overall mortality and morbidity
      rates in the study period were 10% and 31%, respectively. However, a marked
      improvement in survival was recorded in the latter half of the study (17% vs 6%).
      The mortality from Hartmann's resection was also reduced substantially in the
      second half of the study (24% vs 7.5%). These improvements occurred despite
      having a higher number of poor-risk patients (APACHE II score) with more severe
      pathology (generalised peritonitis, 35% vs 50%; faecal peritonitis, 9% vs 25%) in
      the latter half. There was a significantly worse survival in patients who were
      over 70 years of age (P < 0.03), those who had a severe concomitant medical
      illness (P < 0.02), those who had a generalised peritonitis (P < 0.02), and in
      those patients who had an APACHE II score of over 11 (P < 0.05) (Fisher's exact
      test). There was no difference in outcome (morbidity, mortality) between the
      various grades of surgeon involved in performing the emergency surgical
      procedures.

PMID- 7717638
TI  - Avoidable delay in the management of carcinoma of the right colon.
AB  - A retrospective study of 89 consecutive patients with carcinoma of the right
      colon presenting in a district general hospital over a 5-year period is reported.
      Of the patients, 74% were anaemic at the time of diagnosis and 27% of these had
      anaemia or a low mean corpuscular volume (MCV) for a significant time (mean 177
      days, range 76-496 days) before developing symptoms. All doctors should be more
      vigilant towards anaemia or low MCV as presymptomatic indicators of possible
      colonic disease. Appropriate investigation is required in order to detect disease
      at an earlier stage and therefore influence survival. Significant delay in the
      diagnosis of symptomatic disease occurs before referral to hospital (mean 61 days
      vs 36 days, P < 0.05). Treatment delay is similar whether patients are referred
      to surgeons or physicians. The preoperative duration of symptoms for emergency
      admissions was significantly shorter than for elective admissions (mean 50 days
      vs 119 days, P < 0.05). The 30-day mortality was significantly higher for
      emergency admissions (20.7% vs 3.3%, P < 0.05). Earlier diagnosis of symptomatic
      disease may not reduce the proportion of emergency admissions (33%) or improve
      survival. Many tumours are at an advanced pathological stage (39% node positive)
      by the time symptoms develop.

PMID- 7717639
TI  - One-stop diagnosis for symptomatic breast disease.
AB  - A consultant-led one-stop diagnostic service has been available at a busy
      symptomatic breast clinic each week at St Bartholomew's Hospital for 18 months.
      Women can be investigated appropriately using mammography, ultrasonography and
      cytology with immediate reporting. The aim is to achieve a diagnosis and
      management plan for each patient at the initial outpatient visit. A prospective
      audit of four consecutive clinics was undertaken to assess the impact of this
      service on clinical practice. Fifty patients out of 134 new and 386 follow-up
      clinic attenders had one-stop investigations. As a result of immediate reporting,
      48 (96%) patients had a management decision made at the first outpatient visit, 9
      (18%) were offered surgery, and 18 (36%) were discharged with a benign diagnosis
      and no dominant mass. Four symptomatic cancers were detected and evaluated on a
      one-stop basis, constituting 8% of the workload of this clinic. The mean wait
      from designated appointment until surgical consultation was 37.7 min (range -68
      171 min) and that for investigation until subsequent clinical review was 56.9 min
      (range -4-191 min). Thirty-six (72%) one-stop patients had a total wait of less
      than 2 h and 95% were seen in under 3 h. It is felt that the one-stop clinic
      allows optimum patient management, minimises anxiety associated with symptomatic
      breast disease, and maximises utilisation of hospital outpatient resources.

PMID- 7717640
TI  - Limited role for intraoperative intact PTH measurement in parathyroid surgery.
AB  - Primary hyperparathyroidism may be cured surgically by complete excision of
      abnormal parathyroid tissue. Reoperation for persistent hypercalcaemia due to
      residual abnormal parathyroid tissue may be associated with a high complication
      rate. It is possible to assay intact parathormone (iPTH) intraoperatively and as
      iPTH has a relatively short half-life, its measurement intraoperatively may be
      used to predict successful parathyroidectomy. We have studied intraoperative iPTH
      levels in a consecutive series of 33 patients undergoing surgery for primary
      hyperparathyroidism. We found that iPTH levels fell significantly (P < 0.05) from
      a median pre-excision level of 122 pg/ml to a median level of 36 pg/ml 20 min
      after excision. However, in 3/31 successful parathyroidectomies, the
      intraoperative iPTH levels either remained unchanged or had risen. Reliance on
      intraoperative iPTH levels in these patients may have resulted in unnecessary re
      exploration. We conclude that intraoperative iPTH measurement has limited
      usefulness as a predictor of successful parathyroidectomy for primary
      hyperparathyroidism.

PMID- 7717641
TI  - The impalpable testis.

PMID- 7717642
TI  - Neurological complications of high tibial osteotomy--the fibular osteotomy as a
      causative factor: a clinical and anatomical study.
AB  - A clinical study of 105 upper tibial osteotomies was undertaken to investigate
      the incidence, pathology and outcome of perioperative neurological deficit. Motor
      weakness and/or sensory deficit occurred in 21 patients (20%) and in half of
      these the deficit was permanent. For descriptive purposes the fibula was divided
      into four zones. The occurrence of a neurological deficit was clearly related to
      the level of the fibular osteotomy. An anatomical explanation is proposed for
      this complication, based on cadaveric studies. Due to unacceptably high levels of
      complications it is recommended that the fibular osteotomy should not be
      performed in zones II and III (from just below the fibular head to 15 cm distal
      to this level).

PMID- 7717643
TI  - Is there a clinical interaction between low molecular weight heparin and non
      steroidal analgesics after total hip replacement?
AB  - The benefits of parenteral non-steroidal analgesic drugs and low molecular weight
      heparin anticoagulants have been shown before, but there is concern that the use
      of these agents in combination may potentiate haemorrhagic side-effects because
      of simultaneous inhibition of the clotting cascade and platelet mechanisms of
      haemostasis. In a prospective controlled trial, 60 patients undergoing total hip
      replacement were randomised into two groups. Those in one group received
      intramuscular ketorolac and those in the other group opioid analgesia. All
      patients received enoxaparin subcutaneously, once daily. There were 34 patients
      in the NSAID group and 26 in the opiate group. There were no significant
      differences between the two groups for intraoperative blood loss, postoperative
      drainage, transfusion requirements, bruising, wound oozing and leg swelling. From
      this study it would appear that there is a low risk of significant haemostatic
      potentiation associated with concurrent use of low molecular weight heparin and a
      modest dose of ketorolac tromethamine.

PMID- 7717644
TI  - Bicyclist head injury prevention by helmets and mandatory wearing legislation in
      Victoria, Australia.
AB  - After a decade of promotion and education, legislation for mandatory helmet
      wearing by bicyclists in Victoria was introduced on 1 July 1990. The legislation
      was a world first. Comparison of 1710 bicyclist casualties wearing and not
      wearing helmets has demonstrated that wearing helmets certified to the Australian
      Standard reduces the head injury risk by at least 39% and lessens head injury
      severity. Simulated impact testing of helmets has shown that they provide
      protection in most impacts including collisions involving a motor vehicle.
      Legislation for mandatory helmet wearing in Victoria has led to increased wearing
      rates and marked reductions in bicyclist fatalities and head injuries. The
      Victorian experience gives substantial support to the introduction of legislation
      for mandatory helmet wearing by bicyclists.

PMID- 7717645
TI  - The trauma team concept and its implementation in a district general hospital.
AB  - A trauma team approach to the initial assessment, investigation and treatment of
      potentially seriously injured patients has been implemented at a district general
      hospital. Team members are mobilised by an emergency paging system which is
      activated when a patient fulfils one or more of a predetermined list of
      historical, pathophysiological and anatomical criteria. Aspects of the function
      of the trauma team were assessed after 10 months of operation. The problems
      encountered and solutions implemented are discussed. As a result, the structure
      and function of the trauma team has been modified and improved. Although
      hospitals differ in workload and staffing, the trauma team concept is possible
      and achievable at no extra cost. Trauma teams maximise existing resources and
      constitute a valid approach to the early management of the irregular presentation
      of the severely injured patient to district general hospitals. The establishment
      of such teams with members who should be ATLS trained, should be a current
      priority in district general hospitals in the UK.

PMID- 7717646
TI  - Multidisciplinary approach to the management of head and neck arteriovenous
      malformations.
AB  - Arteriovenous malformations (AVM) of the head and neck are quite rare in contrast
      to low-flow vascular anomalies, but often present with significant haemorrhage or
      cosmetic defects. Treatment of these high-flow vascular anomalies is hazardous
      and has a predictably high incidence of recurrence if not managed correctly.
      Intervention is indicated for complications such as pain, haemorrhage, pressure
      symptoms, ischaemic ulceration and even congestive cardiac failure. A
      multidisciplinary team approach is required in the assessment and treatment of
      these lesions, and involves preoperative angiography with superselective
      embolisation, followed by resection of the lesion, ideally within 72 h. Recent
      advances in microsurgery and in therapeutic radiology have greatly improved the
      prognosis for patients with these malformations. We present a series of four
      patients who have undergone preoperative embolisation and subsequent surgical
      excision, with a mean follow-up of 28 months. The complication rate has remained
      low and there has been no re-expansion of the lesions to date.

PMID- 7717647
TI  - Thoracoscopic cardiomyotomy for achalasia of the cardia: early results.
AB  - A thoracoscopic technique of Heller's procedure for achalasia of the cardia is
      described. The operation has been performed on five patients with excellent
      symptomatic results. There were no complications. All patients went home on the
      3rd postoperative day and returned to work within 2 weeks of the procedure.

PMID- 7717648
TI  - Vein factors that affect the outcome of femorodistal bypass.

PMID- 7717649
TI  - Near fatal gas embolism during laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy has been greeted with enthusiasm by surgeons and
      patients alike. However, with the passage of time reports of complications
      related to this new approach are being published. We report an unusual
      complication of gas embolism in laparoscopic cholecystectomy. A high index of
      suspicion along with vigilant intraoperative monitoring will help in the early
      diagnosis and reduction of morbidity associated with gas embolism.

PMID- 7717650
TI  - Laparoscopic cholecystectomy in England and Wales: results of an audit by The
      Royal college of Surgeons of England.

PMID- 7717651
TI  - Cell biology of human vascular smooth muscle.

PMID- 7717653
TI  - Laparoscopic cholecystectomy: potential for missed pathology.

PMID- 7717652
TI  - 3D CT reconstruction in the surgical management of hepatic injuries.
AB  - We employed 3D reconstruction of CT images for evaluation of hepatic injuries in
      a series of eight trauma patients. One had additional reconstruction of a renal
      injury. 3D imaging provided precise anatomical delineation of damaged areas,
      particularly in relation to major vessels. Moreover, the imaging agreed with
      operative findings in every case. The 3D reconstruction facilitated decisions
      regarding intraoperative, reoperative and non-operative management. The improved
      imaging provided by 3D reconstruction may allow hepatic CT scans to be
      interpreted with greater ease and accuracy than conventional CT. We believe this
      is the first report of its use in liver trauma. Current indications may include
      postoperative confirmation of the extent of hepatic injuries, assessment before
      reoperation, and contribution to decisions regarding non-operative management. A
      limitation at present is the time taken for image production, but we suggest that
      in the future 3D imaging might contribute to evaluation before emergency surgery
      in patients with abdominal injuries.

PMID- 7717654
TI  - Assessment of the common bile duct before cholecystectomy using ultrasound and
      biochemical measurements: validation based on follow-up.

PMID- 7717655
TI  - Prevention of phantom pain after major lower limb amputation by epidural infusion
      of diamorphine, clonidine and bupivacaine.

PMID- 7717656
TI  - Dislocation after hemiarthroplasty of the hip: a comparison of the dislocation
      rate after posterior and lateral approaches to the hip.

PMID- 7717657
TI  - A single axillary crease incision for wide local excision and axillary clearance
      in breast cancer.

PMID- 7717659
TI  - [Forum: flaps for covering the the upper limbs.. 1973-1993, 20 years of flaps].

PMID- 7717658
TI  - The acute surgical admission: is mortality predictable in the elderly?

PMID- 7717660
TI  - [Emergency reconstruction using partial transfer of toes. Apropos of 6 cases].
AB  - The authors report on 6 cases for which an emergency toe partial transfer was
      performed for the reconstruction of a thumb or long finger digital segment. In
      most cases, toe pulp transfer was involved, but also partial composite pulp-bone
      nail transfers. Such technique, whose indications seldom apply in an emergency,
      gives better results than conventional techniques (such as homo- and hetero
      digital flaps or distant flaps).

PMID- 7717661
TI  - [Long term evaluation of sensation sequelae of bipedicled digital advancement
      island flaps. Comparison of clinical and electrophysiological results. Apropos of
      13 cases].
AB  - Thirteen homodigital bipedicle island flaps for digital pulp amputation were
      reviewed to allow a better evaluation of sensory sequelae. A clinical and
      electrophysiological study of the sensory score of the pulp were compared to the
      contralateral normal digit and expressed in relative values. Sensory sequelae,
      even minor, are constant. The summated scores of dynamic and static 2 point
      discrimination test, appeared correlated to the electrophysiological amplitude
      modulations. This result seems particularly interesting as it adds another test
      for the objective evaluation of sensitivity.

PMID- 7717662
TI  - [Dorsocommissural flaps. Apropos of a clinical case].
AB  - Dorsocommissural flaps are pedicled flaps with retrograde flow, anastomosed to
      the dorsolateral vessels of the proximal phalanx of one of the two fingers
      adjacent to the site of the commissure flap. The authors describe the anatomical
      basis and operating technique. A clinical case illustrates the simplicity and
      reliability of the technique. The indications for these flaps are digital skin
      defects either palmar involving the proximal phalanx and metacarpophalangeal
      joint, or dorsal involving the middle phalanx and the distal interphalangeal
      joint.

PMID- 7717663
TI  - [Anterior interosseous flap].
AB  - An anatomical study which was carried out on 44 upper limbs of fresh cadavers has
      enabled us to describe a new flap based on the superior perforating branch of the
      anterior interosseous artery: "the anterior interosseous flap". The anterior
      interosseous artery participates in the vascularization of the dorsal aspect of
      the distal two-third of the forearm by providing two perforating branches, "the
      superior and the inferior perforating branches". The superior perforating branch
      of the anterior interosseous artery, pedicle of the flap, perforates the
      interosseous membrane 10 +/- 2 cm above the radio-carpal joint and runs in the
      septum between the extensor pollicis longus and brevis muscles accompanied by two
      venae comitantes. The calibre of the artery at its origin varies from 0.9 to 1.5
      mm. During its course, the artery gives 5 to 7 septocutaneous branches to reach
      the overlying skin in the posterior aspect of the distal two-thirds of the
      forearm. It also gives 3 to 5 osseous branches spreading over the dorsal aspect
      of the distal third of the radius and several muscle branches to the abductor
      pollicis longus, extensor pollicis longus and brevis, extensor indicis and
      extensor digitorum muscles. The inferior perforating branch of the anterior
      interosseous artery generally perforates the interosseous membrane 4 to 5 cm
      above the radio-carpal joint. After giving a medial branch which anastomoses with
      the posterior interosseous artery (in 42 out of 44 cases) the inferior
      perforating branch of the anterior interosseous artery always runs distally to
      join the dorsal vascular network of the wrist which is rich enough to produce a
      retrograde arterial blood flow. This flap can be used as an island flap (with a
      retrograde or a direct blood flow) or a free flap. The surgical procedure of the
      retrograde island flap consists in raising the cutaneous or compound flap based
      on the superior perforating branch, division of the interosseous membrane and
      ligature of the anterior interosseous trunk proximally. The flap is vascularized
      by a retrograde blood flow through the dorsal (or volar or both) vascular network
      of the wrist. Theoretically, the most distal point of rotation of the flap is
      located at the level of the luno-capitate joint and the pedicle is long enough to
      allow the most distal point of the flap to reach the DIP joint of the
      finger.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7717664
TI  - [Simple and composite ulnar transplants in reconstructive surgery of the hand].
AB  - Over several years, the authors have devised a technique for compound island
      transplants of ulnar origin, harvested from the forearm's lower third, with
      reverse flow vascularization. Because of the variety of arterial ramifications,
      these transplants can consist: either of a simple cutaneous, superficial flexor
      tendon or ulnar fragment transplant, or, when associated, of compound cutaneous
      tendinous, cutaneous-osseous and even cutaneous-tendinous-osseous transplants.
      These transplants, based on the clinical experience of 192 cases, can be used by
      retrograde rotation for a variety of indications, such as loss of skin cover,
      digital surface reconstruction or treatment of scaphoid pseudoarthrosis. But
      their main indication, as it represents a basic difference with other retrograde
      flaps, is the possibility of an island transplant of several superficial flexors
      complete with sheats, for the reconstruction of the fingers' flexing system in a
      single surgical act. This is all the more interesting as it is still technically
      possible to combine it with a cutaneous flap, so that the tendinous and cutaneous
      problems can be solved simultaneously. This technique permits reconstruction of
      the fingers' flexor system based on another concept, i.e. by using a vascularized
      tendinous transplant, and under different conditions since a single surgical act
      is required, thus saving long periods of sick leave, with functional results
      which compare with those of traditional techniques.

PMID- 7717665
TI  - [The "star": a design principle of antebrachial radial fasciocutaneous flap.
      Technical note].
AB  - In performing a fasciocutaneous radial forearm flap to cover the dorsum of the
      hand, the authors suggest to draw the flap as an eight-tip star. This technical
      tip allows to minimize the centripetal skin healing process at the recipient site
      (currently observed in case of circular or ovoid defect) and to reduce the scared
      aspect at the donor site, by first closing of the four cardinal tips.

PMID- 7717666
TI  - [The "extreme" brachial flap: a distal pedicled use of an external brachial flap.
      Preliminary report].
AB  - The authors present a new application of the procedure they called the "reverse
      flow YV pedicle extension" which allows a very distal pedicled mobilisation of
      the lateral arm flap. Until now, only the distally based lateral arm flap and the
      ulnar recurrent fascicutaneous island flap could to be transferred distally but
      reached only the proximal third of the forearm. In our experience these flaps did
      not seem to be very reliable. Lengthening of the lateral arm flap pedicle using
      the lateral triceps artery (branch arising from the profunda brachii artery)
      allows the lateral arm flap to be transferred beyond the distal third of the
      forearm. This so-called "extreme" lateral arm flap has advantages and
      disadvantages which are discussed in this paper. We consider cutaneous or
      osteocutaneous reconstructions of the forearm to be the best indication for this
      flap. Our first clinical case is reported.

PMID- 7717667
TI  - [Venous return in the flap with retrograde arterial flow].

PMID- 7717668
TI  - [Flaps for covering extensive losses of cutaneous substance on the upper limb.
      Apropos of 15 cases].
AB  - The authors report on their recent experience concerning flap treatment of upper
      limb complex trauma, based on 15 cases. Proper wound care, and the use of
      healthy, well vascularised tissues for coverage is of paramount importance for
      good results, whose quality mostly depends on the severity of initial lesions.
      The results of this series are encouraging and appear to be a consequence of the
      great possibilities offered by the cutaneous or muscular flaps used.

PMID- 7717669
TI  - [Free transfer in the emergency treatment of complex injuries of the arm. Apropos
      of 18 cases].
AB  - In 18 cases the authors used a free tissue transfer during the first 24 hours of
      the treatment of a complex trauma of the upper limb involving osteoarticular and
      neurovascular loss combined with loss of skin cover. The various flaps include:
      lateral arm flap (8 cases), latissimus dorsi flap (4 cases), toe to hand transfer
      (4 cases), radial forearm flap (2 cases). The series includes 2 failures salvaged
      without further sequelae by means of a groin flap. With regard to complex one
      stage reconstructions, particularly those requiring replacement of bone, the
      outcome is improved if the selected method permits early mobilisation and
      complete cover. Free transfers are to be compared with loco-regional flaps which
      are more reliable but suffer limitations such as a small cutaneous element and,
      frequently, involvement of the pedicle in the mechanism of the trauma. For the
      severe cases in this series, only free tissue transfers provided the adequate,
      immediate cover required to save the traumatised limb.

PMID- 7717670
TI  - [Coverage of arterial repair of the upper limb. Choice of a technique apropos of
      24 cases].
AB  - Twenty-four cases of complex trauma of the upper limb, with soft tissue damage
      including at least loss of part of an artery and the overlying skin, were
      recorded and treated in the Hand Emergency Unit at the Timone Hospital in
      Marseilles. These cases were dealt with globally in a single staged operation
      with careful wound care, bone stabilisation when this was deemed necessary,
      arterial shunt and repair of the soft tissues. To cover the exposed arterial
      shunt, the choice of coverage technique depends on the site of the lesion, on the
      extent of soft tissue damage, and also on the reliability of the flap and its
      residual scar. The authors analyse their series and present their indications.

PMID- 7717671
TI  - [Microsurgical coverage of proximal amputation of the forearm. Functional value
      of preservation of the elbow joint].
AB  - The authors reported three traumatic cases of below-elbow amputation. The
      proximal squeleton of the forearm was bare-exposed and the replantation was not
      done due to the mechanism of the injury. To preserve the function of the elbow
      joint which the main components were safe, the soft tissue coverage was realized
      by a musculocutaneous latissimus dorsi free flap in each case. A body-powered
      forearm prosthesis was adapted for the three patients who were able to return to
      an adapted job in an average time of 8 months. The importance of the preservation
      of the elbow joint to improve the function in upper limb amputees is discussed.

PMID- 7717672
TI  - [Severe injuries of the elbow: emergency coverage and transient
      revascularization. Apropos of 13 cases over a 3-year period].
AB  - Large open elbow fractures with extensive soft-tissue loss must be treated as an
      emergency. Vessels and nerves are often alvulsed. One stage reconstruction is
      very challenging. Ischemia of the distal part of the upper extremity is limited
      by a synthetic arterial shunt (SAS). After debridement, the authors install the
      SAS, then the complex procedure can begin. The authors purpose a new four-stage
      classification and prognostic factors. Debridement concerns crushed, devitalised
      soft and osteo-articular tissues. If it appears possible to salvage the hand and
      forearm with necessity of complex reconstructions (vessels, nerves,
      osteosynthesis, soft tissues) SAS is used. SAS was used 3 times on the group of
      large avulsions with ischemia (5 cases); it was quickly installed between the
      humeral and a distal artery and allowed section of the best distal artery for
      revascularisation. Seven external fixation devices allowed intra operative and
      post operative management of the wound. The coverage of these large, complex
      wounds was performed by the latissimus dorsi transposition flap (2 muscular and 5
      musculo-cutaneous flaps). It should be considered the flap of choice. Local
      flaps, which include local skin transposition, muscle transposition or vascular
      axis, would be contra indicated in a wide zone of injury (the base of these local
      flaps are damaged by high energy trauma) or when distal ischemia is present
      because of arterial axis sacrifice. The dorsal decubitus position, the specific
      dissection of neurovascular pedicle proximally as far as the axillary artery, the
      muscular and cutaneous design can be used to cover anterior, posterior, internal
      and external parts of the elbow. Restoration of elbow function uses an innervated
      latissimus dorsi muscle (3 cases). If only coverage is wanted, this flap has
      significant advantages over local flaps and free transfer procedures when the
      recipient vessels are within the area of injury. Between the donor site and the
      recipient site, the muscular part of the latissimus dorsi flap is placed in an
      arm counterincision. It ensures closure of the elbow joint. Early progressive
      range of movement exercises can be performed.

PMID- 7717673
TI  - [Forum: cover flaps of the upper limb. In practice: indications of pedicled flaps
      of the upper limb].
AB  - The author analyses the historical development and disadvantages of pedicled
      island flaps of the upper limb. The various procedures for skin cover of the
      upper limb are described region by region: shoulder, arm, elbow, forearm, wrist,
      hand and fingers. The large number of these procedures means that the
      reconstructive surgeon would have to be able to master all techniques and
      indications. Adopting an eclectic approach, the author proposes two main flaps:
      the latissimus dorsi muscle to cover the proximal region of the upper limb and
      the pedicled inguinal flap for the distal upper limb.

PMID- 7717674
TI  - [Adipose pad of the external sub-malleolar fossa. Anatomy and value in
      liposuction of the lower limbs].
AB  - The existence of an adipose formation under the skin of the lateral part of the
      ankle is constant in both sexes. It is more important in the female ankle. No
      anatomical study has been made before, except for an illustration in Sarrafian's
      Treatise of Anatomy, where it is described as a "fat pad of the prelateral
      malleolar fossa", whereas no actual description is provided in the text.
      Therefore, there exists no international anatomical definition (PNA) of this
      constant superficial formation, and we propose to adopt Sarrafian's definition
      (in French: C.A.S.M.E.). This fat pad is located directly under the lateral
      malleola, just before the projection of the extensor digitorum brevis muscle. The
      prelateral malleolar fat pad is spontaneously visible, as a redundant tissue, on
      the side of all adult female ankles. The present study includes anatomical
      dissections of seven ankles of fresh cadavers. Its surgical interest resides in
      the fact that it may affect the results of liposuction of the lower extremities,
      because it could be mistaken for a chronic oedema resulting from surgery. In
      ankle liposuction, it will be advisable to perform an additional liposuction of
      this fat pad, with a syringe, to improve results. Therefore it is important to
      perform a systematic examination of this fat pad and to note its clinical
      characteristics before and after surgery in all cases of liposuctions of all
      parts of the lower extremities.

PMID- 7717676
TI  - [Restoration of substance loss on the nose in adults].

PMID- 7717675
TI  - [Harvesting thin and semi-thin skin from the scalp: risks and their prevention].
AB  - The complications of raising scalp grafts are dominated by the risks of
      haemorrhage and alopecia, which can be prevented by careful preparation of the
      donor site, perfect intraoperative coordination and close surveillance of
      epithelialisation. The authors report their experience in the Freyming-Merlebach
      burns unit, with particular emphasis on the value of this technique in children.

PMID- 7717677
TI  - The multiple sclerosis lesion.

PMID- 7717678
TI  - Sodium channel blockade by antibodies: a new mechanism of neurological disease?

PMID- 7717679
TI  - Antibodies against GM1 ganglioside affect K+ and Na+ currents in isolated rat
      myelinated nerve fibers.
AB  - High titers of anti-GM1 ganglioside antibodies (anti-GM1 antibodies) may be
      implicated in lower motor neuron disease. We studied the pathogenic role of anti
      GM1 antibody using the petroleum jelly-gap voltage clamp technique on isolated
      single myelinated rat nerve fibers. Anti-GM1 antisera were obtained from rabbits
      immunized with GM1 ganglioside. Extracellularly applied anti-GM1 antisera without
      complement activity increased both the rate of rise and the amplitude of the K+
      current elicited by step depolarization, with little effect on Na+ current. In
      the presence of active complement, however, anti-GM1 antibodies decreased the Na+
      current, and caused a progressive increase of nonspecific leakage current.
      Neither complement alone nor complement-supplemented antisera from which anti-GM1
      antibodies were depleted by affinity chromatography had any effect on ionic
      current. These observations indicate that anti-GM1 antibodies themselves can
      uncover K+ channels in the paranodal region, while anti-GM1 antibodies bound to
      the nodal membrane in the presence of complement may form antibody-complement
      complexes that block Na+ channels and disrupt the membrane at the node of
      Ranvier.

PMID- 7717680
TI  - Deficits of smooth-pursuit eye movement after unilateral frontal lobe lesions.
AB  - We recorded horizontal smooth-pursuit responses to sinusoidal and step-ramp
      stimuli in 7 patients with unilateral frontal lobe lesions. Five patients had
      directional smooth-pursuit deficits, all with impairment toward the side of
      cerebral damage. Ipsidirectional pursuit defects involved pursuit maintenance to
      sinusoidal targets, pursuit initiation to step-ramp targets, or both. No patient
      had asymmetry of smooth pursuit according to the retinal hemifield of target
      appearance. Smooth-pursuit velocities were subnormal in both horizontal
      directions in 4 patients. The human frontal lobes participate in the initiation
      and maintenance of smooth pursuit in both directions, with a greater ipsilateral
      contribution. Of 5 patients with ipsilateral pursuit impairment, 3 had cerebral
      lesions in the area of the frontal eye field (FEF). These 3 patients also made
      inaccurate saccades to targets moving away from the side of the lesion, implying
      that the FEF transmits motion information to the saccadic system. Two patients
      with ipsidirectional smooth-pursuit defects had cerebral damage that spared the
      FEF, indicating that other frontal regions also contribute to smooth pursuit.

PMID- 7717681
TI  - A clinical and molecular genetic study of dentatorubropallidoluysian atrophy in
      four European families.
AB  - Dentatorubropallidoluysian atrophy is a neurodegenerative disorder with
      characteristic pathology, chiefly described in reports from Japan, and is
      associated with an unstable CAG trinucleotide repeat in a gene on chromosome 12.
      We describe four European families, three British and one Maltese, with this
      mutation. All exhibited autosomal dominant inheritance, and there was evidence
      for anticipation associated with an increase of the expansion with paternal
      transmission in two families. Affected chromosomes from patients with
      dentatorubropallidoluysian atrophy had CAG expansions of 58 to 74 repeats,
      compared to 7 to 26 in control chromosomes, and the size of repeat was
      significantly inversely correlated with age of onset. The clinical features were
      diverse, even within individual families, and comprised a combination of a
      movement disorder (chorea, myoclonus, dystonia, or parkinsonism), cerebellar
      ataxia, epilepsy, psychosis, and dementia. A clinical diagnosis of Huntington's
      disease had been made in affected individuals from all families.
      Neuropathological examination of 2 patients showed no specific abnormality in one
      and degenerative changes predominantly affecting the spinal cord in the other.
      Investigation of 55 patients who might represent sporadic examples of
      dentatorubropallidoluysian atrophy did not detect any expanded alleles.
      Dentatorubropallidoluysian atrophy is likely to be more common than previously
      recognized in non-Japanese populations, and should be considered in any patient
      with a dominantly inherited neurodegenerative disorder with the above-mentioned
      clinical features.

PMID- 7717682
TI  - Pontine ischemic rarefaction.
AB  - To investigate apparently asymptomatic, bilateral symmetrical predominantly
      pontine hyperintensities (PHI) on magnetic resonance imaging (MRI) scans in
      elderly patients, we examined the pons histopathologically in two brains of
      elderly hypertensives with PHI, and in three without PHI, on postmortem MRI
      scans. We also reviewed 85 serial in vivo MRI scans of patients over 60 and
      compared scan findings, vascular risk factors, and clinical symptoms between
      patients with PHI and a control group. A subcortical arteriosclerotic
      encephalopathy (SAE)-like pathology was present in the pons in only the two
      autopsy brains with PHI and corresponded with the location of PHI on the
      postmortem MRI scans and with the most frequent sites of PHI on in vivo scans.
      SAE also involved the hemispheric white matter in one of the autopsy brains. Five
      of 16 (31%) patients with, and 4 of 69 (6%) without, PHI on in vivo MRI scans had
      marked periventricular hyperintensity (PVHI) compatible with SAE (p = 0.01). We
      conclude that an SAE-like pathology may be seen in the pons in elderly
      hypertensives and this pathology is probably the cause of PHI seen on MRI scans
      of patients over 60 years of age.

PMID- 7717684
TI  - Intrinsic epileptogenicity of human dysplastic cortex as suggested by
      corticography and surgical results.
AB  - Cortical dysplastic lesions (CDyLs) are often associated with severe partial
      epilepsies. We describe the electrographic counterpart of this high degree of
      epileptogenicity, manifested by continuous or frequent rhythmic epileptogenic
      discharges recorded directly from CDyLs during intraoperative
      electrocorticography (ECoG). These ictal or continuous epileptogenic discharges
      (I/CEDs) assumed one of the following three patterns: (1) repetitive
      electrographic seizures, (2) repetitive bursting discharges, or (3) continuous or
      quasicontinuous rhythmic spiking. One or more of these patterns were present in
      23 of 34 patients (67%) with intractable partial epilepsy associated with CDyLs,
      and in only 1 of 40 patients (2.5%) with intractable partial epilepsy associated
      with other types of structural lesions. I/CEDs were usually spatially restricted,
      thus contrasting with the more widespread interictal ECoG epileptic activity, and
      tended to colocalize with the magnetic resonance imaging-defined lesion.
      Completeness of excision of cortical tissue displaying I/CEDs correlated
      positively with surgical outcome in patients with medically intractable seizures;
      i.e., three-fourths of the patients in whom it was entirely excised had favorable
      surgical outcome; in contrast, uniformly poor outcome was observed in those
      patients in whom areas containing I/CEDs remained in situ. We conclude that CDyLs
      are highly and intrinsically epileptogenic, and that intraoperative ECoG
      identification of this intrinsically epileptogenic dysplastic cortical tissue is
      crucial to decide the extent of excision for best seizure control.

PMID- 7717683
TI  - Activated T cells of nonneural specificity open the blood-nerve barrier to
      circulating antibody.
AB  - Recent studies from our laboratory and by other investigators have shown that
      autoreactive CD4+ cells specific for peripheral nerve P2 protein have a powerful
      effect on blood-nerve barrier permeability. In this study we injected CD4+ T
      cells reactive to a nonneural antigen (ovalbumin) systemically and achieved their
      accumulation in the tibial nerve of Lewis rats by previous intraneural injection
      of ovalbumin. Selected rats were given systemic demyelinating antibody
      (antigalactocerebroside) to provide an indicator of changes in the permeability
      of the blood-nerve barrier, and the animals were monitored by sequential
      neurophysiological studies and histology. Circulating ovalbumin-specific T cells
      accumulated at sites of intraneural ovalbumin injection without inducing
      demyelination in control animals. In rats with circulating galactocerebroside
      antibodies, local conduction block and demyelination were seen in the region of T
      cell accumulation. Electron microscopy demonstrated dissolution of some tight
      junctions between endothelial cells in areas of T-cell accumulation, and T cells
      traversing the endothelium between endothelial cells and through their cytoplasm.
      Endothelial cell damage was evident in these areas. This study demonstrates
      breakdown of the blood-nerve barrier by activated T cells, even of nonneural
      specificity, allowing the development of focal conduction block and demyelination
      in the presence of circulating antimyelin antibodies.

PMID- 7717685
TI  - Cerebral oxygen supply and utilization during infant cardiac surgery.
AB  - The survival of infants with congenital heart disease has improved dramatically.
      However, the incidence of neurological injury in infants surviving cardiac
      surgery remains considerable. These neurological sequelae are attributable at
      least in part to hypoxia-ischemia/reperfusion, which inevitably accompanies
      infant heart surgery with deep hypothermia, cardiopulmonary bypass, and
      circulatory arrest. To begin to identify mechanisms of brain injury during infant
      cardiac surgery, we used near-infrared spectroscopy to study the relationship
      between cerebral intravascular (hemoglobin) and mitochondrial (cytochrome aa3)
      oxygenation in 63 infants (aged 1 day to 9 months) undergoing deep hypothermic
      repair of congenital heart defects, throughout the intraoperative period.
      Moreover, we assessed the effect of postnatal age on these changes. The cerebral
      concentration of oxidized cytochrome aa3 decreased from the onset of deep
      hypothermic cardiopulmonary bypass, despite apparent abundant intravascular
      oxygenation manifested by a simultaneous increase in the cerebral concentration
      of oxyhemoglobin. During this interval infants older than 2 weeks had a greater
      decrease in oxidized cytochrome aa3 than did infants 2 weeks old or younger.
      During deep hypothermic circulatory arrest, cerebral levels of oxidized
      cytochrome aa3 remained depressed while those of oxyhemoglobin declined. With
      reperfusion following circulatory arrest, the recovery of oxidized cytochrome aa3
      was delayed, despite a rapid recovery of intravascular oxygenation (HbO2). After
      rewarming and 60 minutes of reperfusion, only 46% of infants recovered to the
      baseline level of cerebral oxidized cytochrome aa3. These findings demonstrate a
      paradoxical dissociation of changes in intravascular and mitochondrial
      oxygenation during hypothermic cardiopulmonary bypass; a pronounced decrease of
      mitochondrial oxygenation is established during induction of hypothermia and a
      delay in recovery of mitochondrial oxygenation occurs following circulatory
      arrest. These effects were more pronounced in infants older than 2 weeks than in
      younger infants. The data suggest potentially deleterious impairments of
      intrinsic mitochondrial function or of delivery of intravascular oxygen to the
      mitochondrion or both, effects previously undetected and apparently influenced by
      cerebral maturation.

PMID- 7717687
TI  - Effects of brain-derived neurotrophic factor on motor dysfunction in wobbler
      mouse motor neuron disease.
AB  - Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival
      of developing motor neurons in vitro and to rescue motor neurons from axotomy
      induced cell death in vivo. In this study, we examined the effects of exogenous
      BDNF on the progression of wobbler mouse motor neuron disease (MND). After
      clinical diagnosis at age 3 to 4 weeks, 20 affected mice received subcutaneous
      injections of recombinant human BDNF (5 mg/kg, n = 10) or vehicle (n = 10), three
      times a week for 4 weeks. In a separate experiment done to conduct a histometric
      analysis of the C-5 and C-6 ventral roots and to determine the number of
      myelinated nerve fibers, 7 wobbler mice received identical BDNF treatment. In the
      10 BDNF-treated wobbler mice, grip strength declined at a slower rate (p < 0.03)
      and was twice as great as that of vehicle-treated animals at the end of treatment
      (p < 0.01). In vivo biceps (p < 0.01) and in vitro muscle twitch tensions (p <
      0.02) were also greater than those of vehicle-treated mice. The biceps muscle
      weight was 20% greater (p < 0.05) and the mean muscle fiber diameter was
      significantly larger in BDNF-treated mice (p < 0.001) because the number of small
      (denervated) muscle fibers was markedly reduced. The number of myelinated motor
      axons at the cervical ventral roots studied in the additional 7 affected mice was
      25% greater with BDNF treatment (p < 0.0001). This study establishes that
      exogenous BDNF administration can retard motor dysfunction in a natural MND and
      diminish denervation muscle atrophy and motor axon loss.

PMID- 7717686
TI  - Basement membrane reduplication and pericyte degeneration precede development of
      diabetic polyneuropathy and are associated with its severity.
AB  - In a recent paper, we showed that the number of endoneurial microvessels per
      square millimeter and the average luminal area and size distribution of these
      microvessels are not significantly different in sural nerves of patients with
      diabetes mellitus as compared to control subjects. Mural area, especially the
      component due to basement membrane reduplication and cellular debris, was
      unequivocally increased in diabetes mellitus. Because these latter changes are
      associated with a decrease in periendothelial cell area, we hypothesized that
      cellular degeneration, especially of pericytes, may account for basement membrane
      reduplication and increased frequency of cellular debris. In the present study,
      we showed that endoneurial microvessels undergo a statistically significant
      increase in basement membrane area, mural area, and frequency of cellular debris
      in diabetics without polyneuropathy and an even greater increase in diabetics
      with polyneuropathy. We also found that duration of diabetes mellitus was
      significantly associated with area occupied by reduplicated basement membrane and
      cellular debris, but not with mural and periendothelial area. None of the
      examined measurements was associated with age. Since the microvessel
      abnormalities we describe are already present before the development of
      polyneuropathy and increase with severity of polyneuropathy, it is likely that
      they reflect functional derangements of pericytes and microvessel function which
      precede and might be implicated in fiber degeneration.

PMID- 7717688
TI  - Cerebrospinal fluid levels of amyloid beta-protein in Alzheimer's disease:
      inverse correlation with severity of dementia and effect of apolipoprotein E
      genotype.
AB  - Alzheimer's disease (AD) is characterized by formation in brain of
      neurofibrillary tangles and of amyloid deposits. The major protein component of
      the former is tau, while the latter are composed of amyloid beta-peptides (A
      beta), which are derived by proteolytic cleavage of the amyloid beta-protein
      precursor (APP). Both tau and various secretory APP derivatives including A beta
      and APPS are present in human cerebrospinal fluid (CSF). To investigate whether
      clinical signs of AD are paralleled by changes in CSF levels of these proteins,
      we correlated quantitative measures of dementia severity with CSF concentrations
      of A beta, of APPS, and of tau. We found that levels of A beta in CSF of AD
      patients were inversely correlated both to cognitive and to functional measures
      of dementia severity. In contrast, levels of APPS and of tau did not correlate
      with dementia severity. Apolipoprotein E (apoE) genotype did not influence CSF
      levels of A beta, APPS, or tau, which were similar among AD patients with Apo E
      epsilon 3/3, epsilon 3/4, and epsilon 4/4 alleles. These data indicate that CSF
      levels of A beta decrease with advancing severity of dementia in AD and suggest
      that they are independent of a patient's Apo E genotype.

PMID- 7717689
TI  - Active and passively induced experimental autoimmune encephalomyelitis in common
      marmosets: a new model for multiple sclerosis.
AB  - A chronic relapsing-remitting form of experimental autoimmune encephalomyelitis
      was induced in the common marmoset Callithrix jacchus following a single
      immunization with human white matter. Individual animals in this species are born
      as natural bone marrow chimeras, allowing transfer of functional T-cell
      populations between genetically distinct siblings. The acute disease was
      characterized clinically by mild neurological signs. Pathologically, the disease
      was characterized by perivascular mononuclear cell infiltrates, large foci of
      primary demyelination, and reactive astrogliosis. No animal displayed hemorrhagic
      necrotic lesions or polymorphonuclear cell infiltrates characteristic of other
      acute forms of primate experimental autoimmune encephalomyelitis. A late
      spontaneous relapse occurred in each of 2 animals followed for 3 to 12 months
      subsequent to recovery from the acute attack. In these animals, chronic lesions
      consisted of mononuclear cell infiltrates within large sharply defined areas of
      demyelination and astrogliosis, and resembled active plaques of chronic multiple
      sclerosis. Proliferative responses to myelin basic protein but not to myelin
      proteolipid protein were present in peripheral blood lymphocytes of immunized
      animals. Furthermore, myelin basic protein-reactive T-cell lines derived from
      immunized donors induced clinical signs of experimental autoimmune
      encephalomyelitis when adoptively transferred into a sibling, indicating that
      myelin basic protein-reactive T cells can induce disease in this species. Because
      of its clinical and pathological similarity to human multiple sclerosis and the
      ability to adoptively transfer experimental autoimmune encephalomyelitis, this
      model system should prove useful in the analysis of the immunological mechanisms
      responsible for autoimmune demyelination in outbred primates.

PMID- 7717690
TI  - The role of hypoventilation in a sheep model of epileptic sudden death.
AB  - Unexpected sudden death is a common event in otherwise healthy epileptics, though
      its etiology has remained unclear. Many authors have suggested cardiac
      arrhythmias as the cause, and limited data in humans and animal studies have
      supported this. However, autopsy series in humans have shown pulmonary edema, a
      phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We
      developed a model of status epilepticus in unanesthetized, chronically
      instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine
      levels and seizure type and duration did not differ between animals dying
      suddenly and those surviving. Benign arrhythmias were generated in all animals;
      in no case did an arrhythmia account for the death of an animal. Striking
      hypoventilation was demonstrated in the sudden death group but not in the
      surviving animals. Differences in peak left atrial and pulmonary artery
      pressures, and in extravascular lung water were also demonstrated; pulmonary
      edema did not account for the demise of the sudden death animals. Thus, our model
      of epileptic sudden death supports a role of central hypoventilation in the
      etiology of sudden unexpected death and confirms the association with pulmonary
      edema. The importance of arrhythmia in its pathogenesis is not confirmed.

PMID- 7717691
TI  - Selectively distributed processing of visual object recognition in the temporal
      and frontal lobes of the human brain.
AB  - Evoked potentials to visually driven cognitive tasks were recorded through depth
      electrodes placed bilaterally within the amygdala, hippocampus, midtemporal and
      inferotemporal cortex, and lateral frontal cortex of 6 epileptic patients. Task
      related differential response patterns were used to identify the recording sites
      engaged by specific aspects of visual encoding. In this group of 6 patients, the
      amygdala was most frequently engaged in encoding the familiarity of faces;
      midtemporal and inferotemporal cortex, in encoding perceptual identity and object
      categorization; and lateral frontal cortex, in holding visual object information
      in working memory. The two aspects of encoding that most frequently engaged the
      hippocampal region were related to working memory and object categorization. The
      processing of complex visual knowledge is thus anatomically distributed but
      regionally specialized. These experiments also showed that identical input and
      output parameters can engage different areas of the brain depending on the nature
      of the instructional set.

PMID- 7717692
TI  - Decreased CD3-mediated interferon-gamma production in relapsing-remitting
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system that has been postulated to be T-cell mediated. We examined the
      proliferation and cytokine secretion of mononuclear cells after stimulation with
      OKT3 (anti-CD3) monoclonal antibody concanavalin A, or ionomycin plus myristic
      acid palmityl ester in subjects with stable relapsing-remitting MS. Control
      subjects demonstrated good proliferation to anti-CD3 monoclonal antibody whereas
      subjects with relapsing-remitting MS showed a significantly decreased anti-CD3
      monoclonal antibody-mediated response. There was no difference in concanavalin or
      ionomycin plus myristic acid palmityl ester stimulation between control subjects
      and MS subjects. Secretion of interferon-gamma was significantly decreased and
      transforming growth factor-beta was significantly increased from cultures
      stimulated with anti-CD3 monoclonal antibody, but not ionomycin plus myristic
      acid palmityl ester or concanavalin A, in MS patients compared to control
      subjects. Secretion of interleukin-10 and tumor necrosis factor-alpha was not
      different between control subjects and MS patients following stimulation with
      anti-CD3 monoclonal antibody, concanavalin A, or ionomycin plus myristic acid
      palmityl ester, or of interleukin-2 and interleukin-4 following stimulation with
      anti-CD3 monoclonal antibody or concanavalin A. An abnormality of signal
      transduction and secretion of the immunomodulatory molecule interferon-gamma may
      exist in MS via the CD3 T-cell receptor complex.

PMID- 7717694
TI  - High-tech health care is great, but our first duty is to do no harm.

PMID- 7717693
TI  - Visual system abnormalities in adrenomyeloneuropathy.
AB  - We studied the visual system in 59 men with adrenomyeloneuropathy. Pattern
      reversal visual evoked potentials, magnetic resonance imaging, and clinical
      examination revealed that visual pathways are affected in 63% of patients,
      involving the optic discs, optic nerves, lateral geniculate bodies, optic
      radiations, and parietooccipital cortex. This indicates both primary
      demyelination of the optic nerves and discs, and more diffuse involvement of
      postchiasmal structures.

PMID- 7717696
TI  - Surgical technologists.

PMID- 7717695
TI  - Glove powder.

PMID- 7717698
TI  - Neuroendoscopic laser-assisted ventriculostomy of the third ventricle.
AB  - Hydrocephalus is caused by an imbalance between the production and absorption of
      cerebrospinal fluid. Ventriculostomy of the third ventricle now is an acceptable
      treatment alternative for this problem. This procedure reduces costs over the
      course of the illness because the patient does not require subsequent shunt
      revisions throughout his or her life. The specialized care and the fear
      associated with the dependency on mechanical hardware also are eliminated if
      shunt placement is avoided. Postoperative complications may include increased
      intracranial pressure, bleeding, infection, and pain.

PMID- 7717697
TI  - Transsphenoidal adenomectomy.
AB  - The pituitary gland is a complex organ controlling many of the body's hormonal
      and metabolic functions. The gland's complexity and location in the brain have a
      serious impact on the diagnosis and treatment of pituitary pathology. Several
      surgical approaches are available to treat pituitary tumors; however, the
      transsphenoidal approach allows the surgeon to remove the tumor with minimal
      damage to surrounding intracranial structures. Perioperative nurses should be
      knowledgeable about pituitary pathology (ie, mass effect, hormonal involvement),
      patient treatment options, surgical approaches, and possible postoperative
      complications to provide quality nursing care.

PMID- 7717699
TI  - Interactive, image-guided, stereotactic neurosurgery systems.
AB  - Interactive, image-guided, stereotactic neurosurgery systems and advanced
      computer programs enable neurosurgery teams to use magnetic resonance imaging
      (MRI) and computed tomography (CT) scans to perform less-invasive intracranial
      tumor excisions. This new methodology, also known as frameless stereotactic
      neurosurgery, provides accurate, precise preoperative and intraoperative patient
      information to neurosurgeons. Neurosurgeons use a pointing device to communicate
      surgical locations quickly to a computer system. The computer then provides
      immediate, three-dimensional displays of pertinent MRI and CT scan information on
      the monitor. These intracranial images serve as navigational guides to
      neurosurgeons before and during surgical intervention. Interactive, image-guided,
      stereotactic neurosurgery systems, however, are only surgical tools, not
      substitutes for health care providers' knowledge or expertise. Neurosurgeons must
      balance their medical judgment with interpretations of computer-generated
      information throughout the surgical procedures. Interactive, image-guided systems
      should not interfere with patient care priorities but rather should be worked
      into the intraoperative nursing routine.

PMID- 7717700
TI  - Implementing a baccalaureate perioperative nursing elective.
AB  - To increase perioperative experience and knowledge, operating room staff members
      of a southeastern US veterans affairs hospital and the faculty of a nearby
      college of nursing baccalaureate program developed a perioperative nursing
      elective. The course included both classroom and clinical experiences. Benefits
      to students include the ability to transfer knowledge and skills to other
      clinical settings, increased understanding of the trauma of the surgical
      experience for the patient, and increased interest in a career in perioperative
      nursing.

PMID- 7717701
TI  - Perioperative nurses' perceptions of caring practices.
AB  - This study was designed to determine how caring is practiced in perioperative
      nursing. The theory of nursing by M. Jean Watson, RN, PhD, FAAN, provided the
      conceptual framework for the study. The researcher used a qualitative,
      descriptive methodology to analyze data collected in audiotaped interviews with
      five perioperative nurses and used standard qualitative research procedures for
      transcribing and analyzing the interview data. The five study participants
      identified their perceptions of caring behaviors with conscious and unconscious
      patients in the preoperative, intraoperative, and postoperative periods. They
      described the essential structure of caring as the establishment of a human care
      relationship and provision of a supportive, protective, and/or corrective
      psychological, physical, and spiritual environment.

PMID- 7717702
TI  - A program proposal for new technology assessment.
AB  - New perioperative technology is developing constantly. To ensure the integration
      of quality, effectiveness, efficacy, and efficiency in patient care, an overall
      structure to new technology assessment should be implemented. This program for
      technology assessment, evaluation, and implementation was created to be a
      cohesive process using both human and monetary resources and to incorporate a
      cooperative plan used by all services within the mission of the hospital and
      under the guidance of administrative services.

PMID- 7717703
TI  - Proposed recommended practices for sponge, sharp, and instrument counts.
      Association of Operating Room Nurses.

PMID- 7717704
TI  - Proposed recommended practices for positioning the patient in the perioperative
      practice setting. Association of Operating Room Nurses.

PMID- 7717705
TI  - A summary of AORN's efforts toward achieving recognition and reimbursement for RN
      first assistants.

PMID- 7717706
TI  - Simultaneous measurement of glucose and glutamine in aqueous solutions by near
      infrared spectroscopy.
AB  - A method is described for measuring the concentrations of both glucose and
      glutamine in binary mixtures from near infrared (NIR) absorption spectra. Spectra
      are collected over the range from 5000-4000/cm (2.0-2.5 microns) with a 1-mm
      optical path length. Glucose absorbance features at 4710, 4400, and 4300/cm and
      glutamine features at 4700, 4580, and 4390/cm provide the analytical information
      required for the measurement. Multivariate calibration models are generated by
      using partial least squares (PLS) regression alone and PLS regression combined
      with a preprocessing digital Fourier filtering step. The ideal number of PLS
      factors and spectral range are identified separately for each analyte. In
      addition, the optimum Fourier filter parameters are established for both
      compounds. The best overall analytical performance is obtained by combining
      Fourier filtering and PLS regression. Glucose measurements are established over
      the concentration range from 1.66-59.91 mM, with a standard error of prediction
      (SEP) of 0.32 mM and a mean percent error of 1.84%. Glutamine can be measured
      over the concentration range from 1.10-30.65 mM with a SEP of 0.75 mM and a mean
      percent error of 6.67%. These results demonstrate the analytical utility of NIR
      spectroscopy for monitoring glucose and glutamine levels in mammalian and insect
      cell cultures.

PMID- 7717707
TI  - The effect of cellular energetics on foreign protein production.
AB  - Escherichia coli strain F-122 was used to determine if there are additional
      physiological effects, other than decreasing energetic efficiency accompanied by
      the excretion of the acetate, on foreign protein production. This organism was
      the host for expressing HIV582-beta-galactosidase fusion protein under the
      control of the trp promoter, with ampicillin resistance. By comparing parallel
      batch cultures with and without acetate addition, it was found that the presence
      of acetate in the media did not influence beta-galactosidase activity. In these
      experiments, it appears that the low protein productivity often observed during
      acetate formation is the result of inefficient cell metabolism, rather than
      acetate acting as a specific inhibitor of protein production.

PMID- 7717708
TI  - [Problems in chemosensitivity testing].
AB  - Although chemotherapy is promising as one form of treatment within its field, its
      therapeutic benefit has yet to be fully utilized because drug sensitivity tests
      have not been sufficiently used as predictors of response. The currently
      available prediction accuracy of drug effectiveness is said to be in the range of
      60-69%, while the prediction of their ineffectiveness is reportedly 91-97%. The
      elimination of ineffective drugs is an issue of crucial importance because the
      side effects of carcinostatic agents are severe. It has been argued that in vivo
      effects cannot be accurately predicted on the basis of in vitro results for a
      variety of reasons. There are the roles played by the route of administration,
      intra-cellular distribution and clearance. In addition, there are also the roles
      of pharmacokinetics, structural factors related to spheroidal tumors, variations
      of the micro-cellular environment and so forth in the in vivo situation. To date,
      a short-time clinical usefulness of sensitivity tests has been reported, but
      whether there is predictive value for longer-term survival remains to be
      elucidated.

PMID- 7717709
TI  - [From the aspect of pre-clinical study of new anticancer candidate compounds].
AB  - In the pre-clinical study of anticancer candidate compounds, the following three
      points should be carefully evaluated before decision to enter the clinical
      trials. Namely, 1) the data on the antitumor efficacies (in vitro and in vivo),
      2) animal toxicities and 3) pharmacological studies. Since more attention has
      been placed on the clinical trials to protect the right of cancer patients, the
      toxicity data are especially examined carefully using small and large
      experimental animals. Feasibility to enter in the clinical studies should be
      examined by above three points in the preclinical studies.

PMID- 7717710
TI  - [Phase I study].
AB  - Criticisms and proposals were presented from the standpoint of implementation
      with regard to the objectives, person in charge, test facilities, patients tested
      and test design in the first phase cited in the "Guidelines For Methods To
      Evaluate Drugs for Malignant Tumors at the Clinical Level." Moreover, it was
      proposed that the public be informed as to the need and importance of scientific,
      theoretical and highly cost-efficient clinical trials.

PMID- 7717711
TI  - [Phase II study].
AB  - It is 4 years since the Ministry of Health and Welfare of Japan introduced "The
      Guidelines on Clinical Evaluation for Anti-tumor Drugs" in February 1991. From
      the stand point that I have conducted several clinical studies on new anti-tumor
      drugs according to the Guidelines, this review pointed out some practical
      problems in the process to develop Phase II study based on the Guidelines.

PMID- 7717712
TI  - [Phase III study].
AB  - After a drug is found to have some minimal amount of activity in phase II study,
      the next step is to determine the effectiveness of compared new treatment to no
      treatment or placebo, the best current standard therapy, and toxicity in phase
      III study. Phase III study is the most rigorous and extensive type of scientific
      clinical investigation of a new treatment. Accordingly, much of this issue is
      devoted to the principles of phase III study.

PMID- 7717713
TI  - [Toxicity criteria].
AB  - Toxicity criteria used by the "Japan Society for Cancer Therapy" (JSCT) were
      reviewed and compared with that of WHO, ECOG, NCI (USA), and JCOG. During the
      past ten years, these toxicity criteria of the major cooperative study groups
      have undergone significant revision, but, toxicity criteria of JSCT have never
      been revised for more than ten years. Thus criteria of JSCT now show a several
      inconsistency. Grading of toxicity is also indistinct. Therefore, toxicity
      criteria used by JSCT should be revised. Furthermore, in the assessment of
      toxicity, duration of toxicity, effects of toxicity on the quality of life and
      psychosocial problems should also be considered. Standard criteria for the
      assessment of long-term complications are necessary. To study early signs and
      symptoms of late effects and to know risk factors for toxicity are also
      important.

PMID- 7717715
TI  - [The preventive effect of granisetron on digestive tract symptoms induced by
      arterial infusion of anticancer and hypertensive agents in combination with
      radiotherapy--a study of forty patients with bladder cancer].
AB  - Forty patients with bladder cancer who underwent radiotherapy with angiotensin
      II, a hypertensor, and two cycles of arterial infusion of anticancer
      chemotherapies, including cisplatin 100 mg/body, were randomly assigned to a
      granisetron group and a non-granisetron group for comparative study of its
      prophylactic effect on nausea, vomiting and anorexia. Granisetron proved
      significantly effective in preventing nausea, as 75% of granisetron-administered
      patients experienced either only slight nausea or none at all, against only 22.5%
      in the non-granisetron group. The number of vomiting episodes was zero during the
      three-day observation period in 28 out of 40 (70%) granisetron-administered
      patients compared with 6 patients (15%) in the non-granisetron group. A
      significant difference in prophylactic effect on anorexia was demonstrated
      between the granisetron and non-granisetron group, indicating that control of
      alimentary symptoms such as nausea and vomiting influences the severity of
      anorexia. As to the safety, nausea was lengthened and deteriorated in one
      patients. Though the physician in charge judged it to be an adverse event too
      minor to question the safety of granisetron. Thus, granisetron proved to be
      highly effective and safe in preventing nausea, vomiting and anorexia in patients
      under concomitant administration of radiotherapy with hypertensor and arterial
      infusion of anticancer chemotherapies.

PMID- 7717714
TI  - [Early phase II trial of l-leucovorin and 5-fluorouracil in advanced colorectal
      cancer. l-Leucovorin and 5-FU Study Group].
AB  - We report the results of a multicenter clinical trial comparing three combination
      chemotherapeutic regimens including 5-fluorouracil (5-FU) and l-leucovorin (l
      LV). One hundred and twenty-two patients were randomized to three regimens
      comprising 5-FU (600 mg/m2) plus high-dose l-LV (250 mg/m2) in six doses given
      weekly by i.v. injection midway during a 2-hr infusion of l-LV (regimen A), 5-FU
      (370 mg/m2) plus high-dose l-LV (100 mg/m2) given simultaneously for 5
      consecutive days and a 23-day interval between treatments (regimen B) and 5-FU
      (370 mg/m2) plus low-dose l-LV (10 mg/m2) with the same dose administration
      schedule as regimen B (regimen C). The response rates were 32.4% (12/37 cases) in
      Regimen A, 20.0% (8/40) in regimen B and 11.1% (4/36) in regimen C. The most
      prominent side effects observed in regimen A were diarrhea (53.8%) and leukopenia
      (53.8%); however, they were within permissible levels. The combinations of high
      dose l-LV and 5-FU (regimen A and B) had higher response rates than that of low
      dose l-LV and 5-FU (regimen C). Weekly administration of high-dose l-LV and 5-FU
      (regimen A) is now being expanded to late phase II trials.

PMID- 7717716
TI  - [Effects of anticancer drugs and combination effects of anthracyclines on the
      hypoxic cells of head and neck cancer].
AB  - Head and neck cancer has hypoxic compartment. The hypoxic cells are resistant to
      anticancer drugs and thought to be one of the causes of recurrence. We examined
      effects of anticancer drugs on the hypoxic cells using HEp-2 human laryngeal cell
      line. Anticancer drugs, CDDP, peplomycin (PEP), 5-FU, THP-adriamycin (THP-ADR),
      and adriamycin (ADR), were incubated with cells in hypoxic condition (5% CO2 and
      95% N2) for 72 hours. Drug effects were measured by proliferation rates (IC50).
      IC50 of PEP increased 22.89 folds in hypoxic cells. IC50 of CDDP and 5-FU also
      increased 1.86 and 2.27 folds respectively. However, IC50 of THP-ADR and ADR
      remained same in the hypoxic cells. It was proved that THP-ADR and ADR were
      effective for the hypoxic cells. The combination effect with THP-ADR and CDDP or
      PEP were more than additive against the hypoxic cells. It was suggested that the
      combination with THP-ADR and CDDP or PEP are effective for head and neck cancer
      which contains hypoxic cell compartment.

PMID- 7717718
TI  - [Transfer of carmofur (HCFU) to the serum, bile, pancreatic juice and pancreatic
      tumor tissue in the cases of peri-pancreatic head cancer].
AB  - The concentrations of carmofur, 1-hexyl-carbamoyl-5-fluorouracil (HCFU), in the
      serum, bile, pancreatic juice and pancreatic tumor tissue were studied in 18
      cases of peri-pancreatic head cancer with drainages of the pancreatic and biliary
      ducts after pancreatico-duodenectomy. As a result, high concentrations of HCFU
      and 5-FU were detected in the serum, bile and pancreatic juice after a per-oral
      administration of HCFU, 200 mg: HCFU was high in the order of serum > bile and
      pancreatic juice, and 5-FU in the order of bile, serum and pancreatic juice. Two
      hours after administration, 5-FU concentration in the bile and serum attained to
      the maximum levels of 0.45 and 0.19 micrograms/ml, respectively, which
      demonstrated a lasting transfer of 5-FU to the bile at high concentration. HCFU
      and 5-FU levels in the tumor tissue were 0.079 and 0.024 micrograms/g,
      respectively. In conclusion, antitumor effect against the malignant tumors of the
      pancreatobiliary system can be expected by peroral administration of carmofur.

PMID- 7717717
TI  - [Pharmacokinetic analysis of platinum in the continuous CDDP-CBDCA treatment; its
      relation to the changes of blood biochemistry].
AB  - Seven patients with recurrent gynecological malignancies (2 cervical, 2
      endometrial, 3 ovarian) treated with CDDP at the initial chemotherapy were
      studied for the pharmacokinetic analysis of platinum (Pt) and changes of blood
      biochemistry in the continuous CDDP-CBDCA infusion therapy. All the patients were
      indwelled of the total parenteral nutrition catheter. A balloon type infuser
      (Baxter Inc., multiday type) was connected with the catheter and the drugs were
      infused continuously through it. CBDCA was infused continuously from day 1
      through day 5 at a daily dose of 60 mg/m2, followed by continuous CDDP infusion
      from day 6 through day 30 at a daily dose of 2.5 mg/m2. All the patients received
      3 courses of the treatment. The area under the [Pt]-time curve (AUC) of
      filterable Pt was as high as 60.98 +/- 8.20 mg.hr/ml (mean +/- SE), and that of
      total Pt 691.48 +/- 93.61 mg.hr/ml. However, the Cmax of filterable Pt was as low
      as around 400 ng/ml during day 1 to 6, and around 20 ng/ml during day 7 to day
      30. As to the toxicity, only slight myelosuppression but no renal and
      gastrointestinal toxicity were observed in this therapy. The quality of life of
      the patients received this treatment were maintained well throughout of the
      therapy. Responders were evaluated as 1 CR, 2 PR, 2 NC and 1 PD. These data
      indicated that high AUC but low Cmax of filterable Pt by continuous CDDP-CBDCA
      therapy resulted in less toxicity. Further investigation was warranted to
      evaluate the efficacy of continuous CDDP-CBDCA therapy.

PMID- 7717719
TI  - [Antiproliferative and antimetastatic effects of UFT on MKL-4 human breast cancer
      cells transplanted into nude mice].
AB  - Prospective studies have suggested that postoperative adjuvant chemotherapy for
      breast cancer resulted in a lower recurrence rate and a better survival rate.
      However, there have been little experimental data on the chemotherapeutic agents
      for the suppression of progression of micrometastasis from breast cancer focus.
      We recently established a spontaneous metastasis model of MKL-4 human breast
      cancer cells transplanted into nude mice. In the present paper, both
      antiproliferative and antimetastatic effects of UFT were studied with this
      metastasis model. Oral administration of UFT (20 mg/kg daily) given 4 weeks
      inhibited significantly the growth of MKL-4 tumors in mice. Histological
      examination revealed a massive necrosis in the treated tumors. UFT also seemed to
      decrease the frequency of lymph node and distant metastases. In particular, no
      metastasis was observed in tumor-bearing mice in which the volume of tumors after
      the UFT-treatment was smaller than that before the treatment. It is premature to
      conclude that UFT has an antimetastatic effect because the volumes of the tumors
      of the control group and the treatment groups differed, but at least UFT may have
      an antimetastatic effect.

PMID- 7717720
TI  - [Chemosensitivity test with endoscopic biopsy specimens].
AB  - In SDI test using tetrazolium salt, we compared MTT with XTT, which has been
      recently developed and is more sensitive than MTT. Further, a chemosensitivity
      test with endoscopic biopsy specimens using XTT was conducted. The
      reproducibility of the MTT assay was assessed under various conditions. The I.I
      of MTT assay did not vary according to type or concentration of anticancer drugs
      and the biopsy site of specimens. Then MTT and XTT assay were compared, revealing
      the results of these 2 assays were significantly correlated. Thus, XTT assay was
      performed with tissues from surgical specimens using biotome. Of the 16 specimens
      subjected to XTT assay, 6 showed an OD value of 0.100 or more, which was well
      within assessment. XTT assay was also performed in biopsy specimens from patients
      using a biotome manipulated under endoscopic guidance before operation. Three
      among 6 specimens showed an OD value of 0.100 or more. Our findings have
      demonstrated that the SDI test using XTT can be used for the chemosensitivity
      test, even when these specimens contain a relatively small number of cells
      collected using a biotome.

PMID- 7717721
TI  - [Malignancy of gastric cancer analyzed by the expression of thymidine
      phosphorylase].
AB  - In this study, the expression of thymidine phophorylase (dThdPase) was
      investigated immunohistochemically in 73 patients with gastric cancer. dThd Pase
      was mainly distributed at the apical portion, or cytoplasm of cancer cells and
      its expression was detected in 52 tumors (71.2%). There were no significant
      association among the expression of dThdPase, histologic type, depth of invasion,
      and lymph node metastasis. However, a significant difference was noted with
      respect to liver metastases. Among 73 patients, liver metastases were observed in
      11 patients. dThdPase expression was detected in all of these cases with liver
      metastases, which was significantly more common than those without such
      metastases. In relation to the prognosis, patients with dThdPase-positive tumors
      had a significantly worse prognosis than those with dThdPase-negative tumors. In
      conclusion, the expression of dThdPase may be useful as a predictor of malignant
      potential in gastric cancer.

PMID- 7717722
TI  - [A case of small cell lung cancer with renal insufficiency effectively treated
      with oral etoposide administration].
AB  - A 74-year-old woman with left-sided heart failure was admitted to our department
      with abnormal shadow in the right lung. Chest X-P and CT scans showed a tumor
      shadow measuring 2.5 cm in the right lower lobe and mediastinal lymphnode
      swelling. Cytological examination of needle biopsy specimen revealed small cell
      carcinoma (cT1N2M0). Elevations of tumor marker, NSE and CEA were noticed at 11.8
      and 12.7 ng/ml, respectively. Considering complications including renal
      insufficiency and heart failure in the case, 2 courses of oral etoposide (25
      mg/body) for 21 consecutive days were performed. The tumor shadow decreased
      remarkably in size and complete response (CR) was obtained. Side effects were all
      tolerable. A pharmacokinetic study of etoposide revealed serum etoposide levels
      of more than 1.0 microgram/ml on day 15. These results suggest that oral
      etoposide administration is an effective regimen in small cell lung cancer
      patients associated with renal insufficiency.

PMID- 7717724
TI  - [Improvement of recurrent lung metastasis of breast cancer by Zoladex and
      cyclophosphamide].
AB  - The patient was a 38-year-old woman who was diagnosed as having right breast
      cancer (T1aN1bM0, stage II) at the age of 36 when she underwent right mastectomy.
      Postoperative adjuvant therapy was performed using UFT and tamoxifen. After 2
      years and 4 months, pulmonary metastasis was diagnosed from elevated tumor
      markers and chest X-P. After the relapse, treatment with goserelin acetate
      (Zoladex) and CPA was started. After 2 months of this treatment, the tumor in the
      lung had shrunk in size, and after 5 months partial remission (PR) was evaluated
      from improvements in chest X-P and normalization of tumor markers, This PR
      condition continues at present. A case report is presented of a patient with
      premenopausal recurrent breast cancer in whom good results were obtained by
      concomitant administration of Zoladex and CPA.

PMID- 7717725
TI  - [Evaluation of 5-FU, leucovorin, etoposide, and cisplatin (FLEP) chemotherapy by
      hepatic artery injection in the treatment of multiple liver metastases from
      gastric cancer].
AB  - We performed FLEP chemotherapy (consisting of 5-FU, leucovorin, etoposide, and
      cisplatin) by hepatic artery injections for three patients with multiple liver
      metastases from gastric cancer, and two of three resulted in partial response
      (PR). We presented two PR cases. Case 1 is a 57-year-old male with multiple liver
      metastases from gastric cancer. Distal partial gastrectomy with regional
      lymphadenectomies were carried out, and an injection port was implanted in the
      hepatic artery. We performed FLEP chemotherapy from 16 days after the operation.
      Liver metastases subsided and resulted in PR after 3 months by CT scan. He is now
      healthy and working for 15 months after the operation. Case 2 was a 49-year-old
      female with multiple liver metastases from gastric cancer. Total gastrectomy with
      regional lymphadenectomies was carried out. We performed FLEP chemotherapy by
      hepatic artery injections from 21 days after the operation. The response of
      chemotherapy resulted in PR by CT scan, and she is now healthy and has been
      working for 11 months after the operation. Thus, this form of chemotherapy may be
      useful for patients with multiple liver metastases from gastric cancer.

PMID- 7717723
TI  - [A case of chest wall tumor associated with production of CA125 treated
      effectively by chemotherapy].
AB  - A 61-year-old female was admitted to our hospital because of a mass in right
      lateral chest wall and chest pain. Chest X-P and CT scans showed a right chest
      wall tumor and pleural effusion. Biopsy specimen from the chest wall tumor
      revealed an adenocarcinoma, not a mesothelioma, based on immunohistochemical
      study. Cancer cells were also detected in pleural effusion. Imaging diagnostic
      analysis could detect no primary tumor in lung field or other organs. High levels
      of CA125 were noticed: 9,610 U/ml in serum and 37,600 U/ml in pleural effusion,
      respectively. Finally, there was a possibility that the chest wall tumor might be
      a metastatic lesion from undetected ovarian cancers, so three cycles of combined
      chemotherapy (CDDP+ADM+CPA) were done. CDDP plus OK-432 was also injected two
      times intrapleurally. After chemotherapy, the chest wall tumor and effusion
      disappeared and the serum CA125 level decreased to the normal range.

PMID- 7717727
TI  - [Important prognostic factors in surgically treated gastric cancer patients].
AB  - In order to clarify important factors in prognosis of patients with gastric
      cancer, 3,515 surgically treated cases were investigated. The survival rate
      varied widely depending on the curativity which strongly correlated with the
      stage of the disease. For example, such cases with peritoneal dissemination and
      hepatic metastasis have a poor prognosis. According to our multivariate
      investigation by Cox's proportional hazard model (SAS, PHREG procedure) based on
      resectable cases of gastric cancer, the most significant prognostic factor was
      lymph node metastasis with a ratio of risk 4.58, followed by the macroscopic-type
      cancer, ratio of risk 3.61, and depth of invasion, with the ratio of risk 2.22.
      It should be noted that such factors as macroscopic type of cancer turned out to
      be an important prognostic factor aside from those related with the stage of
      cancer, such as lymph node metastasis and depth of invasion. Type 4 gastric
      cancer had a markedly poor prognosis. Among all surgically treated patients, the
      histologic type was insignificant as a prognostic factor, however, when limited
      to mucosal cancer, the undifferentiated type had a higher lymph node metastasis
      rate than the differentiated type. This result suggests that the histologic type
      of cancer should be carefully considered in case of endoscopic treatment of
      gastric cancer.

PMID- 7717726
TI  - [Expression of vascular endothelial cell growth factor as a predictor of
      recurrence in gastric carcinoma].

PMID- 7717728
TI  - Respiratory syncytial virus--how soon will we have a vaccine?

PMID- 7717729
TI  - Late diagnosis of congenital sensorineural hearing impairment: why are detection
      methods failing?
AB  - This study was designed to look in detail at the paths to diagnosis for a group
      of 197 children with congenital sensorineural hearing impairment (SNHI), who were
      diagnosed between 1989 and 1991 in the state of Victoria, Australia. Despite the
      existence of universal infant screening at 7-9 months by distraction test or
      questionnaire, the median age at diagnosis for the study group was 18.0 months,
      with median age at aid fitting of 20.8 months, and median age at commencement of
      specialised intervention programmes of 22.3 months. Parent questionnaires
      completed for 143 (73%) of these children showed that 49% had known risk factors
      for hearing loss yet only 20% of them had been referred for audiological
      assessment before the 7-9 month screen. Only 63% of those eligible for the 7-9
      month screen had received it. Of those children who were screened by distraction
      test 46% passed as did 57% of those screened by questionnaire. Twenty four
      parents (17%) described how they had initially 'denied' their own observations of
      their infants' abnormal hearing behaviour. When concerns were raised with
      professionals, 10% of parents were falsely reassured without audiological
      assessment. Detection methods are failing through a combination of poor screen
      test efficacy, incomplete population coverage, and parental and professional
      denial.

PMID- 7717730
TI  - Lung function, airway responsiveness, and respiratory symptoms before and after
      bronchiolitis.
AB  - Acute viral respiratory illness during infancy has been implicated as a precursor
      for subsequent lower respiratory morbidity in childhood. A prospective,
      longitudinal study of respiratory function, airway responsiveness, and lower
      respiratory illness during early childhood was performed in a cohort of 253
      healthy infants to characterise those who experienced bronchiolitis. Seventeen
      infants (7% of the cohort), were given a diagnosis of bronchiolitis during the
      first two years of life with two (1%) requiring hospital admission. Seventy one
      per cent of those infants with bronchiolitis had a family history of atopy, 53%
      of asthma, and 29% had a mother who smoked cigarettes. These family history
      characteristics in this group with bronchiolitis were not different from the rest
      of the cohort. There were also no differences in the number of older siblings,
      the number breast fed, the duration of breast feeding, or socioeconomic status of
      the families between those that did and did not get bronchiolitis. Respiratory
      function was assessed at 1, 6, and 12 months of age. Maximum flow at functional
      residual capacity (VmaxFRC) was measured using the rapid thoracic compression
      technique. Resistance (Rrs) and size corrected compliance (Crs/kg) were obtained
      from a single brief occlusion at end inspiration. Airway responsiveness was
      assessed by histamine inhalation challenge and the provocation concentration of
      histamine resulting in a 40% fall on VmaxFRC from baseline (PC40) was determined.
      Respiratory measurements were ranked into terciles to assess the distribution of
      infants who developed bronchiolitis through the cohort. Cough and wheeze were
      noted to be frequent before the episode of bronchiolitis. This study has
      demonstrated that infants who develop bronchiolitis have evidence of pre-existing
      reduced respiratory function and lower respiratory symptoms. It is proposed that
      bronchiolitis, although potentially contributory, is not usually causative of
      subsequent lower respiratory morbidity.

PMID- 7717731
TI  - Intravenous immunoglobulin in juvenile dermatomyositis--four year review of nine
      cases.
AB  - Juvenile dermatomyositis is difficult to treat, compounded by complications of
      the disease itself as well as side effects of treatment. The mainstay of
      pharmacological management is corticosteroids, to which the disease is usually
      very responsive, but steroids have well established short and long term side
      effects. Refractory cases may be resistant to steroids or patients may become
      dependent on high doses, with relapse in clinical disease precipitated by
      reduction. Overtreatment with steroids and too rapid a reduction are common
      errors. Various second line agents have been used with success in complex or
      refractory cases, including cyclophosphamide, methotrexate, and cyclosporin.
      Intravenous immunoglobulin has been tried in the management of autoimmune
      diseases, either as an alternative to cytotoxic treatment or as a steroid sparing
      agent. The reported benefit in a number of childhood illnesses, including
      juvenile dermatomyositis, prompted this clinical trial in some of our more
      refractory cases. Over the past four years, nine children attending a
      dermatomyositis clinic have been treated with intravenous immunoglobulin. The two
      main indications were failure of conventional treatment and severe side effects
      from previous treatment, principally corticosteroids. All nine were still on
      treatment with various permutations of prednisolone, azathioprine, and
      cyclosporin. All nine showed clinical improvement at some point in their
      treatment with intravenous immunoglobulin. Of eight children on concurrent
      prednisolone, the dose could be reduced in six and kept the same in two.

PMID- 7717732
TI  - Genetic difference in HLA-DR phenotypes between coeliac disease and transitory
      gluten intolerance.
AB  - Genetic differences in HLA phenotypes were studied in coeliac disease to
      investigate why some patients do not react with mucosal damage after gluten
      challenge. Forty five children with coeliac disease and 16 with transitory gluten
      intolerance were typed; 76 subjects served as controls. HLA phenotypes in
      children with coeliac disease had significantly higher proportions of DR3/X and
      DR5/7 than controls (48.8% v 11.8% and 26.7% v 5.3%). Children with transitory
      gluten intolerance had lower DR3/X (43.8%) than children with coeliac disease and
      there were no DR5/7 phenotypes. Further analysis of similarly well defined cases
      might show whether genetic differences in the DR3/X and DR5/7 phenotypes can
      serve as a marker for the permanence of gluten intolerance.

PMID- 7717733
TI  - Fragile X syndrome.

PMID- 7717734
TI  - DNA testing for fragile X syndrome in schools for learning difficulties.
AB  - Fragile X syndrome is the most common inherited cause of mental retardation.
      Early diagnosis is important not only for appropriate management of individuals
      but also to identify carriers who are unaware of their high risk of having an
      affected child. The disorder is associated with a cytogenetically visible fragile
      site (FRAXA) at Xq27.3, caused by amplification of a (CGG)n repeat sequence
      within the gene at this locus designated FMR1. Clinical and molecular studies
      have been undertaken to screen for fragile X syndrome in 154 children with
      moderate and severe learning difficulties of previously unknown origin. Southern
      blot analysis of peripheral blood showed the characteristic abnormally large
      (CGG)n repeat sequence associated with fragile X syndrome in four of the 154
      children. The findings were confirmed by cytogenetic observation of the fragile
      site and by further molecular studies. The families of the affected children were
      offered genetic counselling and DNA tests to determine their carrier status.
      These findings show that there are still unrecognised cases of fragile X
      syndrome. Given the difficulty of making a clinical diagnosis and the
      implications for families when the diagnosis is missed, screening in high risk
      populations may be justified. The issues involved in screening all children in
      special schools for fragile X syndrome are discussed.

PMID- 7717735
TI  - Body mass index centile charts to assess fatness of British children.
AB  - Body mass index (BMI) relates weight to height and reflects the shape of a child,
      but because of age dependency it has not been used conventionally for the
      estimation of fatness in children. From measurements of Tayside children (n =
      34,533) centile charts were constructed for BMI (wt/ht2) from the raw data of
      height and weight, using Cole's LMS method for normalised growth standards. These
      data were compared with the only available European BMI charts published from
      data of French children obtained over a period of 24 years from 1956-79. British
      children appear to be 'fatter'. Within a subgroup (n = 445) the BMI values were
      correlated with estimations of body fat, for boys and girls, from skinfold
      thickness (r = 0.8 and 0.81) and bioelectrical impedance (r = 0.65 and 0.7). The
      limits of acceptable BMI have yet to be defined.

PMID- 7717736
TI  - Volumetric control of continuous haemodialysis in multiple organ failure.
AB  - A system for precise volumetric control of continuous haemodialysis and its use
      in providing renal replacement treatment in the intensive care unit to 10
      children with multiple organ failure are described. The system, termed slow
      efficient dialysis, provided effective clearance of urea, creatinine, potassium,
      and phosphate. It provided precise control of the volume of ultrafiltrate removed
      in a prospective manner ('dial up' fluid balance) to reduce haemodynamic
      instability and fluid management problems. The ease of use of this system for
      intensive care nurses meant that the system ran without the assistance of a
      second intensive care or renal nurse.

PMID- 7717737
TI  - Myocarditis and haemolytic uraemic syndrome.
AB  - A 13 year old girl is reported who presented with haemolytic uraemic syndrome
      (HUS) due to Escherichia coli O157:H7 infection. She died during the acute phase
      of the illness after an episode of unexplained sudden circulatory collapse.
      Postmortem examination confirmed the diagnosis of HUS and showed histological
      evidence of myocarditis manifested by the presence of inflammatory cell
      infiltration in the myocardium and around the conducting system.

PMID- 7717738
TI  - Double blind placebo controlled trial of pizotifen syrup in the treatment of
      abdominal migraine.
AB  - Fourteen children with abdominal migraine were treated with pizotifen and placebo
      in a double blind crossover trial. The results showed pizotifen to be clearly
      superior to placebo in the prophylaxis of abdominal migraine. The importance of
      clearly distinguishing abdominal migraine from other forms of recurrent abdominal
      pain is emphasised.

PMID- 7717739
TI  - Viable versus inactivated lactobacillus strain GG in acute rotavirus diarrhoea.
AB  - The effect of viable or heat inactivated human Lactobacillus casei strain GG on
      rotavirus immune responses in patients with rotavirus diarrhoea was assessed.
      Rotavirus serum IgA enzyme immunoassay antibody responses were higher in infants
      treated with viable L casei strain GG than in those treated with inactivated L
      casei strain GG. There was a significant difference at convalescence with
      rotavirus specific IgA secreting cells found in 10/12 infants receiving viable
      but only 2/13 infants receiving inactivated L casei strain GG. The results
      indicate that viable L casei strain GG stimulate rotavirus specific IgA antibody
      responses, theoretically significant in the prevention of reinfections.

PMID- 7717740
TI  - Cytomegalovirus retinitis in AIDS.
AB  - Cytomegalovirus retinitis is common in adults with AIDS but has been reported
      infrequently in children with perinatally acquired HIV infection. The cases are
      presented of two infants with vertically acquired HIV infection who developed
      disseminated cytomegalovirus infection and retinitis, and who posed difficult
      management issues.

PMID- 7717741
TI  - Transient neonatal diabetes and later onset diabetes: a case of inherited insulin
      resistance.
AB  - A 13 year old girl who had had transient neonatal diabetes developed permanent
      diabetes. She had raised fasting insulin concentrations suggestive of insulin
      resistance with a suboptimal insulin response to glucose loading. Both her mother
      and sister had profound insulin resistance; neither had clinical diabetes. This
      is the first time inherited insulin resistance has been implicated in the
      pathogenesis of permanent diabetes developing after transient neonatal diabetes.

PMID- 7717742
TI  - Diagnosing respiratory syncytial virus by nasal lavage.
AB  - Nasal lavage was compared with nasopharyngeal aspiration for diagnosis of
      respiratory syncytial virus infection. Nasal lavage and nasopharyngeal aspiration
      were performed on 50 occasions in 32 infants (median age 5.6 months) with acute
      viral wheezing. Compared with nasopharyngeal aspiration, nasal lavage had a
      positive predictive value of 95.6% and negative predictive value of 92.5%. These
      comparable results and lack of adverse effects make nasal lavage the preferred
      method.

PMID- 7717744
TI  - Clinical examination compared with anthropometry in evaluating nutritional
      status.
AB  - Clinical assessments of nutritional status in a group of 44 inpatients, made by a
      panel of experienced childcare specialists, were compared with anthropometric
      assessments. Assessors were uniformly poor at detecting severe malnutrition and
      at assessing the nutritional status of infants. Nutritional status cannot be
      accurately assessed clinically and anthropometry is crucial.

PMID- 7717743
TI  - Suffocation, choking, and strangulation in childhood in England and Wales:
      epidemiology and prevention.
AB  - The causes, classification, and prevention of mechanical asphyxial death in
      children were examined. The Office of Population Censuses and Surveys (OPCS)
      identified children, under 15 years of age, who had died as a result of choking,
      suffocation, or strangulation in England and Wales during the years 1990 and
      1991. Cases in the International Classification of Diseases (ICD) codes of E911
      3, E953, E963, and E983 were selected and case details from HM coroners' records
      and the death certificates were extracted. The OPCS identified 136 children (99
      boys, 37 girls) in the two year period, 65% were under 3 years of age. The
      children were classified as dying from choking (21 cases), aspirating gastric
      contents (39 cases), suffocation (29 cases), strangulation (11 cases), and
      hanging (36 cases). The strangulation cases could be further subdivided into a
      group of 12 younger children who were suspended from ligatures around the home
      and a group of 21 boys (8-14 years) who died of self initiated hanging. Overall,
      11 children were deliberately killed and 31 children died in beds or cots.
      Children whose deaths are classified as being due to aspiration of vomit appear
      to be cases of the sudden infant death syndrome or background medical conditions.
      This study suggests the need for advice on maintaining a safe sleeping
      environment. Only one child choked on a toy and European Standards for Toy Safety
      appear to have been successful. The prevention of hanging in the group of older
      boys needs further exploration.

PMID- 7717745
TI  - Seizure activity causing loss of cardiac output after a Fontan operation.
AB  - After a Fontan operation pulmonary blood flow is heavily dependent on
      respiration. Two patients with a Fontan and normal sinus rhythm developed
      episodes of collapse with loss of cardiac output secondary to the tonic phase of
      an epileptic fit. The forced expiratory effort during the tonic phase severely
      compromised systemic venous return and led to collapse due to loss of cardiac
      output.

PMID- 7717746
TI  - Tryptase and IgE concentrations in the respiratory tract of infants with acute
      bronchiolitis.
AB  - It has been proposed that a specific IgE response contributes to the
      immunopathology of acute respiratory syncytial virus (RSV) bronchiolitis but
      previous work has been difficult to replicate. Indirect evidence that might
      support this contention was sought by measuring total IgE concentrations in
      bronchoalveolar lavage (BAL) samples obtained from intubated infants and by
      attempting to detect mRNA for IgE in cells obtained from both the upper and lower
      respiratory tract. Evidence of significant mast cell activation was sought by
      measuring tryptase concentrations in BAL fluid and serum. Detectable
      concentrations of IgE were found in two of seven BAL samples obtained more than
      five days after intubation and mRNA for IgE was demonstrated in three of six BAL
      samples and three of six samples obtained from the upper respiratory tract.
      Tryptase was detectable in 11 of 12 BAL samples with the two highest values
      detected on day 1. These values were raised compared with control samples but
      were not such to suggest that mast cell degranulation is the major contributor to
      the inflammatory process. These results suggest that IgE may be produced in the
      airways of infants in response to RSV infection. The relationships between IgE
      production, RSV infection, and symptoms of acute bronchiolitis remain obscure.

PMID- 7717747
TI  - Some reservations about clinical guidelines.

PMID- 7717748
TI  - Questionnaire design.

PMID- 7717749
TI  - Congenital hypothyroidism: optimal management in the light of 15 years'
      experience of screening.

PMID- 7717751
TI  - Screening in infancy.

PMID- 7717752
TI  - Changes in deep body temperature before cot death.

PMID- 7717750
TI  - Earlier identification of biliary atresia and hepatobiliary disease: selective
      screening in the third week of life.

PMID- 7717753
TI  - Patterns of obesity in boys and girls after treatment for acute lymphoblastic
      leukaemia.

PMID- 7717754
TI  - Audit of neonatal intensive care.

PMID- 7717755
TI  - Central nervous system tumours--lack of national studies.

PMID- 7717756
TI  - Familial occurrence of congenital laryngeal clefts.

PMID- 7717758
TI  - Female genital mutilation.

PMID- 7717757
TI  - Malnutrition as a prognosis factor in lymphoblastic leukemia: a multivariate
      analysis.

PMID- 7717759
TI  - Effects of pesticides on isolated rat hepatocytes, mitochondria, and microsomes
      II.
AB  - Twenty-two pesticides were examined in vitro for their effects on hepatocytes,
      mitochondria, and microsomes isolated from male rats. Twelve pesticides reduced
      non-protein sulfhydryl (NPSH) content in hepatocytes to less than 80% of control
      at a concentration of 10(-3) M. Chlorothalonil and ziram were especially
      effective, reducing NPSH content at 10(-4) M after 90 min incubation. Among those
      pesticides, only copper terephthalate and chlorothalonil were reactive with
      glutathione non-enzymatically and enzymatically, respectively. Lipid peroxidation
      in hepatocytes was stimulated by four pesticides, namely, chlorothalonil,
      pretilachlor, ethoprofos, and metribuzin at 10(-3)-10(-4) M. Cell viability was
      considerably decreased following incubation with chlorothalonil, trichlamide, and
      ziram. Hepatotoxicity of trichlamide was considered to be associated with its
      direct adverse effects on mitochondrial energy production, since it uncoupled
      isolated mitochondrial respiration at 10(-6) M and depleted cellular ATP content
      prior to cell death. Conversely, chlorothalonil- and ziram-induced hepatotoxicity
      seemed to be related to their depleting effects on cellular sulfhydryls, since
      addition of the thiol compound dithiothreitol to the hepatocytes incubation
      mixture protected cells. With respect to isolated mitochondrial respiration, four
      pesticides inhibited state 3 and/or state 4 respiration rates at 10(-3)-10(-4) M,
      whereas seven pesticides uncoupled state 4 respiration at 10(-3)-10(-6) M. With
      respect to isolated microsomal lipid peroxidation, three pesticides were
      peroxidative at 10(-3)-10(-4) M, whereas three pesticides were antioxidative at
      10(-3)-10(-7) M. Only two pesticides, beta-endosulfan and metalaxyl, had
      essentially no effects on any parameters tested at 10(-3) M.

PMID- 7717760
TI  - Flow cytogenetic analysis of whole cell clastogenicity of herbicides found in
      groundwater.
AB  - Agronomic practices followed in recent years have caused the agrarian sector to
      depend heavily on agri-chemicals such as herbicides, but herbicides have negative
      environmental consequences. Their usage has resulted in chemicals being
      introduced into the groundwater. Although the contaminants are in trace amounts,
      little is known about their potential clastogenic effects at low concentrations.
      In the present study, the potential of flow cytometric analysis to detect the
      whole cell clastogenic properties of low level chemical exposure is examined.
      Chinese Hamster Ovary (CHO) cells were exposed to three herbicides (atrazine,
      bentazon and simazine) and two known clastogens (adriamycin and ara-C) at low
      concentrations for 48 h. Nuclei were isolated from control as well as treatments
      and analyzed by flow cytometry. The clastogenic property was assessed by
      measuring the coefficient of variation (CV) of G1 peaks in different treatments.
      Exposure to known clastogens resulted in increasing CVs with increasing
      concentrations. Flow cytometry was a very accurate and sensitive technique for
      the whole cell clastogenic assay. The results indicated that atrazine has the
      potential to cause whole cell clastogenicity, even at a very low concentration.
      Bentazon showed indications of clastogenic potential but the increases in CVs
      observed with this herbicide were not statistically significant. The CVs are
      unaffected by simazine exposure, thus indicating that simazine does not cause
      whole cell clastogenesis under short term exposure. Flow cytometry proved to be
      an excellent tool for assaying the clastogenic potential of agri-chemicals.

PMID- 7717761
TI  - Patterns of chlorinated biphenyl congeners in harbor seals (Phoca vitulina) and
      in their food: statistical analysis.
AB  - Patterns of chlorinated biphenyl (CB) congeners have been compared in two groups
      of samples, namely blood samples from harbor seals (Phoca vitulina) and muscle
      tissue samples in the fish with which the seals were fed. The data originate from
      a Dutch controlled feeding study, performed in 1981 and 1983. The seals were
      living in captivity in two separate groups, and the fish samples were plaice
      (Pleuronectes platessa) from the Dutch part of the Wadden sea and mackerel
      (Scomber scombrus) from the Atlantic ocean. The levels of CB congeners were
      different in the two types of fish. The CB congener patterns of these four
      "matrices" were compared by analysis of principal components, and were found to
      be different in the two groups of harbor seals, which were fed the different
      types of fish. The corresponding CB congener patterns of the two groups of fish
      were also different. There was no indication for a relatively larger impact of
      biotransformation due to induction of isoforms of the cytochrome P450-system at
      the higher absolute CB congener levels in the Wadden sea group of seals compared
      to the Atlantic group of seals. The differentiation between the CB congener
      patterns in the two groups of seals in the Dutch study can be ascribed solely to
      different CB congener patterns in their food. The difference between CB congener
      patterns in the seals and in their diet can be explained by the structure-related
      biotransformation of the CB congeners in the harbor seal.

PMID- 7717762
TI  - Micro-spatial variations of heavy metals in the teeth of walrus as determined by
      laser ablation ICP-MS: the potential for reconstructing a history of metal
      exposure.
AB  - This study explored the possibility of using laser ablation inductively-coupled
      plasma-mass spectroscopy to measure trace metals and other elements within the
      annual growth layers of the teeth of walrus harvested from the Canadian Arctic.
      Using sample ablation "footprints" of 125 microns diameter on transects across
      the exposed cross-sections of teeth, this technique detected Pb, Cu, Zn and Sr,
      but not Cd, in tooth cementum. The micro-spatial patterns of elements were
      consistent among different transects on the same tooth, and revealed subtle
      differences between animals of different ages. The youngest walrus in the sample
      (4 yr) contained higher concentrations of Pb and Cu than older animals in the
      growth layer deposited during the first year of life, while the oldest animal (33
      yr) exhibited higher Pb and Zn than younger animals in the outer layer
      corresponding to the year 1988. The differences between animals and across annual
      layers may reflect both life history and metal exposure phenomena, including high
      amounts of metals transferred from mothers to pups in maternal milk. The ability
      to detect metals in a repeatable fashion within annual growth layers suggests
      that metal exposure histories accurate to within a year might be re-constructed
      for the life-times of long-lived animals, and that a series of such individual
      studies would allow exposure histories covering centuries to be quickly
      assembled. These data may suggest the most likely explanation for the currently
      high levels of some metals observed in certain Arctic marine mammals, i.e.,
      natural phenomenon or anthropogenic contamination.

PMID- 7717763
TI  - Growth responses of achlorophyllous Euglena gracilis to selected concentrations
      of cadmium and pentachlorophenol.
AB  - The growth response of a wild achlorophyllous Euglena gracilis mutant was studied
      during exposure to cadmium and pentachlorophenol (PCP). Cadmium gradually reduced
      the growth rate and terminal cell density; PCP only lengthened the initial lag
      phase relative to control cultures. Flow cytometry showed that cadmium altered
      the cell cycle by delaying late S and G2/M phases; PCP did not disturb the cell
      cycle, but markedly affected DNA staining: the intercalating dyes ethidium
      bromide and propidium iodide showed little staining compared to controls.
      However, replication and transcription processes were not altered by PCP, as cell
      division occurred normally. Cells surviving after PCP treatment apparently
      developed an adaptative response during the lag phase.

PMID- 7717764
TI  - Occupational exposure to extreme temperature and risk of testicular cancer.
AB  - A study of 250 patients with pathologically confirmed testicular cancer diagnosed
      between January 1977 and June 1980 and 250 population controls matched for age
      and residence was carried out to investigate risk factors for testicular cancer.
      This paper reports results of risk associated with occupational exposure to
      extreme (< or = 60 degrees F or > or = 80 degrees F), high (> or = 80 degrees F),
      and low (< or = 60 degrees F) temperature. Interviews of approximately 1.5 h
      duration were conducted by trained male interviewers, using a standardized
      interview schedule. Mantel-Haenszel methods and logistic regression models were
      employed to estimate these temperature effects on risk of testicular cancer. The
      estimated adjusted odds ratios of testicular cancer, when 16 potential
      confounders were controlled for, were 1.71 (95% Cl: 1.13-2.60) for occupational
      exposure to extreme temperatures; 1.70 (1.04-2.78) for low temperature; and 1.20
      (0.80-1.80) for high temperature. The findings suggest that occupational exposure
      to extreme, low, and high temperature may increase risk of testicular cancer,
      independent of other potential risk factors.

PMID- 7717765
TI  - Asbestos body formation in the human lung: distinctions, by type and size.
AB  - The fraction of fibers coated in a total of 3,800 asbestos fibers from 38
      patients with disease related to asbestos (100 fibers per patient) was
      determined, according to asbestos fiber type and size parameters. Among the 3,800
      fibers, 638 (16.8%) were coated and 3,162 were uncoated. All fibers were analyzed
      at 2,000 x magnification (lower limit of detection: 2 microns for length and 0.06
      microns for diameter). The diameter of the totally coated fibers (28.4% of total
      bodies; 181/638) was not measured. The percentage of coated fibers varied with
      the asbestos type; it was 27.1% (335/1235) for amosite fibers, 16.0% (228/1423)
      for crocidolite, 6.6% (60/908) for tremolite or actinolite, 6.5% (14/214) for
      anthophyllite, and 5% (1/20) for chrysotile fibers. Most coated fibers were
      longer than 10 microns and had an aspect ratio (length/diameter) of more than 20.
      Approximately 60% of coated fibers had an aspect ratio of more than 100. The
      longer the fiber, the greater the percentage of coated fibers, regardless of
      diameter. The increase in the percentage associated with length was more marked
      in fibers with a smaller diameter; the percentage of coated fibers was,
      therefore, greater in fibers 30 microns or less in diameter. However, in fibers
      longer than 30 microns, the relationship to percentage of coated fibers was not
      as clear, and the diameter was less important. Accordingly, the fibers with high
      aspect ratios, particularly long fibers, tended to show asbestos body formation.
      The percentage of long fibers was highest in amosite, and the percentage of
      fibers with an aspect ratio of more than 100 was highest in amosite and
      crocidolite.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717766
TI  - Use of hospital discharge data for surveillance of chemical-related respiratory
      disease.
AB  - Hospital discharge data can be useful in the identification of the more severe
      cases of both work- and nonwork-related chemical-related respiratory disease. The
      medical records of 329 patients hospitalized in Michigan in 1989 and 1990 for
      respiratory conditions resulting from chemical fumes and vapors (International
      Classification of Diseases diagnostic code 506) were reviewed to determine the
      location and etiology of the exposures. One-third of the discharges were work
      related. The most common exposures at work were to chlorine and sulfur dioxide
      and to industrial cleaning agents. Exposure to smoke from house fires and
      exposure to household cleaners were the most frequent causes of the nonwork
      related discharges. Follow-up inspections at the work facilities where the
      hospitalized patients with work-related disease had become ill revealed that 61
      of 261 (23.4%) fellow workers interviewed had new adult-onset asthma or were
      bothered at work by daily or weekly symptoms of shortness of breath, wheezing, or
      chest tightness. Nine of the 23 facilities inspected were cited for violating
      Occupational Safety and Health Administration standards.

PMID- 7717767
TI  - Lead, blood pressure, and cardiovascular disease in men.
AB  - Animal studies have demonstrated that relatively low doses of lead can produce
      modest elevations in blood pressure. During the past 10 y, many epidemiologic
      studies have examined the relationship between low-level lead exposure and blood
      pressure in humans. These studies were reviewed in a consensus conference, which
      concluded that the evidence supported the existence of a causal association;
      however, no formal meta-analysis has been conducted. Epidemiologic studies of
      blood lead and systolic blood pressure in males were analyzed in the present meta
      analysis. A highly significant and moderately consistent association was found,
      i.e., decrease of blood lead from 10 mg/dl to 5 mg/dl associated with a decrease
      of 1.25 mm Hg (95% CI = 0.87-1.63 mm Hg). The association was robust to deletion
      of the most significant study or the addition of eight additional studies showing
      no effect. Given the strong animal data, which also implicate a mechanism
      (disturbance of calcium messenger system regulation of blood pressure) present in
      humans, the association should be considered causal.

PMID- 7717768
TI  - Fungus allergens inside and outside the residences of atopic and control
      children.
AB  - Airborne fungi were collected during the peak fungus season, using the N6
      Andersen sampler inside and outside the homes of 46 asthmatic children, 20 atopic
      children, and 26 nonatopic control children in the Taipei area. The geometric
      mean fungus concentrations of the asthmatic, atopic, and control groups were
      found to be 565, 411, and 608 colony-forming units (CFU) per m3 in the living
      rooms; 659, 464, and 602 CFU m3 in the bedrooms; and 547, 449, and 668 CFU m3
      outdoors; respectively. Aspergillus, Cladosporium, and Penicillium were observed
      to be the most common microfungi, both indoors and outdoors. High correlations
      between indoor fungus levels (living rooms or bedrooms) and the corresponding
      outdoor levels were observed for these predominant genera. With regard to the
      Aspergillus species composition, A. flavus and A. niger were observed to be
      predominant and are, therefore, recommended to be included on a skin test panel.
      Moreover, among these three groups, there were statistically significant
      concentration differences for Cladosporium and Penicillium.

PMID- 7717770
TI  - Trihalomethane concentrations in swimmers' and bath attendants' blood and urine
      after swimming or working in indoor swimming pools.
AB  - The influence of working or swimming in indoor swimming pools on the
      concentrations of four trihalomethanes (haloforms) in blood and urine was
      investigated. Different groups (bath attendants, agonistic swimmers, normal
      swimmers, sampling person) were compared. The proportions of trihalomethanes in
      blood and urine correlated roughly with those in water and ambient air. Higher
      levels of physical activity were correlated with higher concentrations. Within
      one night after exposure in the pool the blood concentrations usually were
      reduced to the pre-exposure values. Secretion of trichloromethane in urine was
      found to be less than 10%.

PMID- 7717769
TI  - Effects on respiratory morbidity of occupational exposure to carbon black: a
      review.
AB  - Carbon black is a substance of world importance, both in terms of tonnage
      production and its special ability to strengthen rubber. Its carbonaceous nature
      and respirable size give rise to concern regarding its effect on respiratory
      morbidity for those involved in its manufacture and use. A number of studies have
      used chest radiographs, spirometry and respiratory symptoms as means of assessing
      the various populations, but almost all of the studies have either methodological
      shortcomings or fail to report the necessary detail. However, exposure-related
      effects are evident in those populations studied in terms of small opacities,
      reduction in forced expiratory volume in 1 s and forced mid-expiratory flow, and
      symptoms of chronic bronchitis.

PMID- 7717771
TI  - Lead, erythrocyte protoporphyrin, and hematological parameters in normal maternal
      and umbilical cord blood from subjects of the Riyadh region, Saudi Arabia.
AB  - A survey was undertaken among 124 pregnant women living in Riyadh City to
      investigate the passage of lead from the pregnant mother to the unborn child. The
      mean maternal blood lead level was 5.49 +/- 2.6 micrograms/dl and for the
      umbilical cord was 4.14 +/- 1.81 micrograms/dl. Lead levels were higher in
      maternal than in the umbilical cord blood. The results are in agreement with
      other studies. In this study, an excellent correlation between the maternal and
      cord blood lead levels (r = .83, p < .0001) confirms the transfer of lead from
      the mother to the fetus. A weak but significant relationship was found between
      maternal blood lead concentrations and birth weight of newborns (r = -.271, p <
      .05), and it is concluded that low levels of lead exposure to pregnant women may
      be considered hazardous.

PMID- 7717772
TI  - Immunologic analyses of peripheral leukocytes from workers at an ethical
      narcotics manufacturing facility.
AB  - Little information exists about possible adverse health effects associated with
      workplace exposure to opiate compounds. We have previously reported opiate
      specific IgG antibodies, positive epicutaneous tests, and pulmonary function
      decrements in workers exposed occupationally to opiates. In the present work, we
      extended these findings to investigate the effect of occupational opiate exposure
      on lymphocyte subpopulations and mitogen-induced lymphoblastogenesis. Thirty
      three opiate-exposed workers and 8 nonexposed control workers were evaluated for
      lymphocyte subpopulation absolute numbers and percentages, by evaluating cell
      surface antigen expression with flow cytometry. A complete blood count with
      differential, common clinical chemistry parameters, and serum immunoglobulin
      levels were also evaluated. Opiate-exposed workers showed significantly (p < .05)
      increased absolute numbers and percentages of HLA-DR+ cells (MHC class II
      histocompatibility antigen), significantly (p < .01) decreased percentages of T
      helper-inducer (CD4+) cells, and significantly (p < .05) decreased numbers of
      basophils, compared with nonexposed opiate workers from the same factory. A trend
      toward reduction in the T helper-inducer (CD4+)/T cytotoxic-suppressor (CD8+)
      lymphocyte ratio was also evident. There was also a significant decrease in
      lymphocyte activity stimulated by pokeweed mitogen (p < .05) in opiate-exposed
      workers. These data indicate that occupational opiate exposure may change the
      number and types of circulating peripheral blood leukocytes, or alternatively,
      alter the expression of receptors on the surface of these cells. In addition,
      occupational opiate exposure appears to decrease the sensitivity of B-cells to
      pokeweed mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717773
TI  - The metabolic response to laparoscopic cholecystectomy.

PMID- 7717774
TI  - Elective laparoscopic cholecystectomy nearly abolishes the postoperative hepatic
      catabolic stress response.
AB  - OBJECTIVE: Surgery results in a catabolic state of postoperative stress, where
      the efficiency of the liver to convert amino acids to urea is increased. This
      study measured the metabolic consequences of the less traumatic laparoscopic
      surgery in elective cholecystectomy compared with traditional open surgery
      technique. SUMMARY BACKGROUND DATA: The authors previously have shown that open
      cholecystectomy doubles the urea synthesis measured by the means of the
      functional hepatic nitrogen clearance. Glucagon and cortisol increased by 50% (p
      < 0.05) and 75% (p < 0.05), respectively, after open cholecystectomy. METHODS:
      Patients undergoing uncomplicated elective laparoscopic cholecystectomies were
      included. Preoperatively and on the first postoperative day, blood and urine
      samples were drawn every hour under basal conditions and during amino acid
      infusion. The urea synthesis rate was calculated from the urea excreted in urine
      and accumulated in total body water. Functional hepatic nitrogen clearance was
      quantified as the slope of the linear relation between blood amino-N
      concentration and the urea synthesis rate. The results were compared with an
      historic matched group of patients who underwent open cholecystectomies and were
      studied by the same protocol. RESULTS: The laparoscopic cholecystectomy increased
      the functional hepatic nitrogen clearance by only 25% (from 8.7 +/- 0.9 to 11.1
      +/- 1.5 mL/sec [mean +/- SEM; p < 0.05]), compared with a doubling after open
      cholecystectomy (from 9.4 +/- 0.9 to 17.6 +/- 3.3 mL/sec [p < 0.05]). The
      difference between the groups was significant (p < 0.05). Neither glucagon nor
      cortisol increased significantly after laparoscopic cholecystectomy. CONCLUSIONS:
      The laparoscopic technique results in a much smaller postoperative hepatic
      catabolic stress response and probably reduced tissue loss of amino-N. This may
      be important for the more rapid convalescence and reduced postoperative fatigue.

PMID- 7717776
TI  - Laparoscopic omental patch repair for perforated peptic ulcer.
AB  - OBJECTIVE: The authors' initial experience with laparoscopic omental patch repair
      for perforated peptic ulcer is documented. Its results are compared with those of
      other procedures and follow-up study is reviewed. SUMMARY BACKGROUND DATA: Since
      the advent of H2-antagonists, the usefulness of simple closure of a perforated
      peptic ulcer is increasing, and improvements in laparoscopic surgery have made
      possible minimally invasive surgery for perforated ulcer. METHODS: From December
      1992 to February 1994, laparoscopic omental patch repair followed by use of H2
      antagonists was performed successfully in 11 patients. Fifty-five patients
      underwent other surgical procedures for perforated peptic ulcers (conventional
      open omental patch: 4, selective vagotomy in combination with antrectomy: 24,
      distal gastrectomy: 27). RESULTS: The average operation time was 135 minutes.
      Administration of postoperative pain medication was reduced remarkably (0.9 times
      per patient), and all patients recovered rapidly. No serious postoperative
      complications were recorded. After a mean period of 11 months, the postoperative
      evaluation was satisfactory for all patients, and no ulcer recurrence was found.
      CONCLUSIONS: In perforated peptic ulcer disease, laparoscopic omental patch
      repair offers a number of advantages. Because no upper abdominal incision is
      made, there is decreased postoperative pain, and the patient rapidly recovers
      with fewer and less severe complications. Although the procedure requires a
      surgeon with particular expertise in endoscopic suturing technique, surgeons
      familiar with laparoscopic cholecystectomy can readily perform it after some
      practice. The authors' preliminary experience suggests that this is a minimally
      invasive procedure for perforated peptic ulcer that offers an attractive
      alternative to open surgery.

PMID- 7717777
TI  - The Whipple resection for cancer in U.S. Department of Veterans Affairs
      Hospitals.
AB  - OBJECTIVE: The authors compiled the results after Whipple resection for cancer
      from a large U.S. national hospital system. METHODS: Computerized hospital and
      death benefits records for patients treated with Whipple resection for cancer
      from 1987 to 1991 in U.S. Department of Veterans Affairs hospitals were analyzed,
      excluding lymphomas and neuroendocrine tumors. Institutional tumor registrar
      reports allowed TNM staging in 45% of these cancers. RESULTS: Whipple resections
      were performed in 252 patients with pancreatic cancer and 117 with other
      periampullary cancers. Complications occurred in 37%, and 30-day operative
      mortality was 8%. Postoperative sepsis was associated with a higher operative
      mortality rate. In patients with staged tumors, 5-year survivors were found only
      in those without lymph node involvement. CONCLUSIONS: Whipple resection can cure
      cancer in or near the head of the pancreas when lymph nodes are not invaded by
      tumor. Complications occur in nearly 40% of patients, whereas operative mortality
      rate is related to the average age of the patient population.

PMID- 7717775
TI  - The emerging multifaceted roles of nitric oxide.
AB  - Nitric oxide (NO) is a highly reactive free radical with a multitude of organ
      specific regulatory functions. Since 1985, NO has been the subject of numerous
      research efforts and as a result, has been found to play a major role in the
      cardiovascular, pulmonary, gastrointestinal, immune, and central nervous systems.
      In addition, deranged NO synthesis is the basis for a number of pathophysiologic
      states, such as atherosclerosis, pulmonary hypertension, pyloric stenosis, and
      the hypertension associated with renal failure. Traditional NO donors such as
      sodium nitroprusside and new pharmacologic NO adducts such as S-nitrosothiols may
      serve as exogenous sources of NO for the treatment of NO-deficient pathologic
      states. This review is an attempt to acquaint the surgical community with the
      fundamentals of NO biochemistry and physiology. Increased knowledge of its
      functions in normal homeostasis and pathologic states will enable physicians to
      better understand these disease processes and utilize new pharmacologic
      therapies.

PMID- 7717778
TI  - Trophic response of gut and pancreas after ileojejunal transposition.
AB  - OBJECTIVE: The authors determined whether ileojejunal transposition (IJT)
      stimulates the growth of the pancreas or the nontransposed segment of small
      intestine, and ascertained whether this trophic effect is altered by the location
      of transposed gut segment. SUMMARY BACKGROUND DATA: Transposition of the ileum to
      the proximal small intestine stimulates a marked mucosal growth of the transposed
      ileal segment; the cellular mechanisms responsible for this adaptive hyperplasia
      are not known. METHODS: The distal quarter of the small intestine (distal ileum)
      was transposed into the proximal (Type I), middle (Type II), or distal (Type III)
      portions of the remaining small intestine. On postoperative day 28, the pancreas
      and scraped mucosa from the segments of transposed ileum, proximal ileum, and
      duodenum were obtained, weighed, and examined for DNA and protein content.
      RESULTS: All types of IJT increased mucosal weight and DNA content of the
      transposed ileum. Types I and II IJT produced a significant proliferation of the
      pancreas and mucosa of the duodenum and proximal ileum. The magnitude of
      proliferative increases was greatest in Type I IJT. CONCLUSIONS: Ileojejunal
      transposition appears to be an excellent model to examine the mechanisms by which
      intestinal epithelial cells proliferate in response to luminal nutrients or
      humoral factors.

PMID- 7717780
TI  - Management and outcome of abdominal shotgun wounds. Trauma score and the role of
      exploratory laparotomy.
AB  - OBJECTIVE: The management and outcome of 138 abdominal shotgun wounds were
      examined over a 5-year period. SUMMARY BACKGROUND DATA: It has been proposed that
      exploratory laparotomy may be unnecessary and even overused in a subset of
      patients with abdominal shotgun wounds. METHODS: Data on shotgun wound patients
      from October 1987 through March 1992 from a statewide trauma registry were
      examined. Patients with abdominal shotgun wounds were identified and compared
      with patients with nonabdominal shotgun wounds. RESULTS: Of 516 shotgun wound
      patients, 138 (26.7%) had abdominal wounds and 88 (63.8%) had exploratory
      laparotomies. Abdominal shotgun wounds resulted in significantly longer number of
      intensive care unit days (4.3 vs. 2.5, p < 0.05), a greater number of blood units
      transfused (7.8 vs. 2.4, p < 0.05), and a higher mortality (15.9% vs. 4.8%, p <
      0.05) when compared with nonabdominal shotgun wounds. When stratified for trauma
      score, the mortality for abdominal shotgun wounds always was significantly
      greater than for nonabdominal shotgun wounds. All abdominal shotgun wound
      patients with trauma scores less than ten died. The negative laparotomy rate for
      abdominal shotgun wound patients with normal trauma scores was 9.4%. No patient
      with a negative laparotomy died. CONCLUSION: Abdominal shotgun wounds are a
      particularly lethal subset of shotgun wounds. Although some abdominal shotgun
      wound patients can be managed without laparotomy, the morbidity and mortality for
      these injuries are substantial, even in patients with normal trauma score.
      Clinical judgment is an excellent predictor of the need for laparotomy.

PMID- 7717779
TI  - Intravenous contrast medium aggravates the impairment of pancreatic
      microcirculation in necrotizing pancreatitis in the rat.
AB  - BACKGROUND: Previous reports demonstrated that radiographic contrast medium, as
      used in contrast-enhanced computed tomography, increases acinar necrosis and
      mortality in experimental pancreatitis. The authors studied the possibility that
      these changes may be related to an additional impairment of pancreatic
      microcirculation. METHODS: Fifty Wistar rats had acute pancreatitis induced by
      intraductal glycodeoxycholic acid (10 mmol/L for 10 min) and intravenous cerulein
      (5 micrograms/kg/hr for 6 hrs). After rehydration (16 mL/kg), pancreatic
      capillary perfusion was quantified by means of intravital microscopy at baseline
      before intravenous infusion of contrast medium (n = 25) or saline (n = 25), and
      30 and 60 minutes thereafter. In addition to total capillary flow, capillaries
      were categorized as high- or low-flow (> or < 1.6 nL/min). RESULTS: Pancreatic
      capillary flow did not change in either high- or low-flow capillaries after
      saline infusion. However, contrast medium infusion induced a significant decrease
      of total capillary flow (p < 0.001). Analysis according to the relative flow rate
      revealed that this was primarily because of a significant additional reduction of
      perfusion in low-flow capillaries (p < 0.0001). Furthermore, complete capillary
      stasis was observed in 15.9 +/- 3.4% after contrast medium as compared with 3.2
      +/- 1.2% after saline infusion (p < 0.006). CONCLUSION: Radiographic contrast
      medium aggravates the impairment of pancreatic microcirculation in experimental
      necrotizing pancreatitis.

PMID- 7717781
TI  - The natural history of appendicitis in adults. A prospective study.
AB  - OBJECTIVE: The authors relate prehospital delay and in-hospital delay to the
      incidence of perforation of appendicitis. SUMMARY BACKGROUND DATA: Quality
      assurance studies use perforation rate as an index of quality of care. This is
      based on the assumption commonly presented in retrospective reports that in
      hospital delay to surgery influences the incidence of perforation. Only one
      limited study prospectively found that prehospital delay increased the
      perforation rate. METHODS: During a 6-month period, 95 consecutive adults
      undergoing appendectomies at Foothills Hospital in Calgary, Alberta, were
      questioned as to onset and type of first symptom (i.e., epigastric discomfort,
      anorexia nervosa, vomiting, and abdominal pain). Time of emergency room (ER)
      arrival, surgery consultation, and operating room start were taken from the
      chart. Surgical and pathology reports were used to identify status of appendix
      (normal, inflamed, suppurative, gangrenous, perforated) and presence of abscess
      cavity. The status of appendix was related to prehospital and in-hospital delay
      to establish significance. RESULTS: There were 13 (14%) normal, 67 (70%)
      inflamed, and 15 (16%) perforated appendices. Patients with perforated appendices
      waited 2.5 times longer before reporting to the ER, compared with patients with
      inflamed appendices (57 hours vs. 22 hours, p < 0.007). Once in the hospital,
      patients with perforated appendices were identified and treated faster than those
      with inflamed appendices (7 vs. 9 hours, p < 0.039). Analysis by ER physician was
      3 hours whether the appendix was normal, inflamed, or perforated. Analysis by the
      surgeon was significantly shorter in patients with perforated appendices than
      patients with inflamed appendices (4 vs. 6 hours, p < 0.039). CONCLUSIONS: This
      prospective study identifies that delay in presentation accounts for the majority
      of perforated appendices. Clinical evaluation is effective for identifying
      patients with more advanced disease. Indiscriminate appendectomy as an attempt to
      decrease perforation is not supported by these data. Hospital perforation rates
      likely reflect patient factors, illness attitude, and access to medical care.

PMID- 7717782
TI  - Pretreatment with enteral cholestyramine prevents suppression of the cellular
      immune system after partial hepatectomy.
AB  - OBJECTIVE: The authors tested the hypothesis that the beneficial effects of the
      endotoxin-binding agent cholestyramine on the postoperative course in rats that
      had undergone a partial hepatectomy was the result of improvement of cellular
      immune functions. SUMMARY BACKGROUND DATA: Major liver resection is associated
      with severe postoperative complications and a high incidence of systemic
      infections. Gut-derived endotoxins previously were shown to be involved in the
      pathogenic processes after partial hepatectomy in rats. In addition, enteral
      cholestyramine improved postoperative survival, but how its beneficial effects
      are mediated is not clear. METHODS: Rats that were force-fed for 7 days with
      either cholestyramine (150 mg/day) or 0.9% saline (equal volume) were randomized
      to undergo a partial hepatectomy or a sham operation. After 24 hours, the rats
      were killed and splenic mononuclear cells were tested in vitro for mitogenic
      responses and cytokine production. RESULTS: Proliferative responses of splenic B
      and T lymphocytes and lipopolysaccharide-stimulated production of tumor necrosis
      factor and interleukin-1 by splenocytes were lower in rats after partial
      hepatectomy than in sham-operated animals. An increased concanavalin A-stimulated
      production of interleukin-2 also was found after partial hepatectomy compared
      with sham levels. Pretreatment with enteral cholestyramine preserved cellular
      proliferative responsiveness of both B and T cells, and restored cytokine
      production by splenocytes to sham levels. CONCLUSION: Prophylactic treatment with
      enteral cholestyramine preserved cellular immune functions after partial
      hepatectomy in the rat, which may explain its beneficial effects on the
      postoperative course. Furthermore, the authors' results are consistent with the
      hypothesis that endotoxemia is involved in the pathogenesis of the cellular
      immune derangements after partial hepatectomy.

PMID- 7717783
TI  - Hepatic resection for hepatocellular carcinoma. An audit of 343 patients.
AB  - OBJECTIVE: The authors summarize the results of patients who had hepatectomy for
      hepatocellular carcinoma over a 22-year period. SUMMARY BACKGROUND DATA: Recent
      reports showed improved perioperative results and long-term prognosis. METHODS:
      The perioperative outcome of 343 patients was studied according to three
      different time periods: before 1987 (n = 149); 1987 to 1991 (n = 128); and 1992
      to present (n = 66). Survival analysis was made by stratifying patients into two
      categories--either before or after 1987. The majority of patients had large
      tumors (78%), cirrhosis (73%), and a major hepatectomy (73%). RESULTS: Besides an
      increased resectability rate (23%), there was a marked reduction of the recent
      morbidity (32%; p < 0.001), operative (4.5%; NS) and hospital (6%; p < 0.02)
      mortality rates. The recent surgical approach was identified as a significant
      contributory factor to the lowered hospital mortality rate. Patients in the
      latter part of the study had significantly better survival, with a 1-, 3- and 5
      year survival rate of 68%, 45%, and 35%, respectively. Early detection and
      effective treatment of recurrences contributed to the improved prognosis.
      CONCLUSIONS: The recent management strategy and technological advances improved
      the results of surgical treatment for patients with hepatocellular carcinoma.

PMID- 7717786
TI  - Who decides who decides? When disagreement occurs between the physician and the
      patient's appointed proxy about the patient's decision-making capacity.

PMID- 7717784
TI  - Elemental diet and IV-TPN-induced bacterial translocation is associated with loss
      of intestinal mucosal barrier function against bacteria.
AB  - OBJECTIVE: The goal of the current study was to directly assess the role of loss
      of mucosal barrier function in nutritionally induced bacterial translocation.
      BACKGROUND: Parenteral and certain elemental enteral diets have been shown to
      promote bacterial translocation. The mechanisms underlying this observation,
      especially the question of whether nutritionally induced bacterial translocation
      is primarily related to loss of intestinal barrier function, versus an impaired
      immune system, remain to be fully elucidated. METHODS: Bacterial translocation
      was measured in vivo, ileal mucosal membranes were harvested, and their
      electrophysiologic properties and barrier function were measured ex vivo in the
      Ussing chamber system 7 days after receiving total parenteral nutrition solution
      parenterally (IV-TPN) or enterally (elemental diet). Chow-fed rats served as
      control subjects. RESULTS: The incidence of bacterial translocation was
      significantly increased both to the mesenteric lymph nodes in vivo and across the
      in vitro Ussing chamber-mounted ileal mucosal membranes of the elemental diet-fed
      and IV-TPN-fed rats. The magnitude of Escherichia coli and phenol red
      transmucosal passage in the Ussing chamber was significantly higher in the IV-TPN
      fed rats than in the elemental diet-fed or chow-fed animals. The potential
      differences across the ileal membrane were similar between the three groups at
      all time points. However, the specific resistances of the ileal membranes of the
      IV-TPN and elemental diet groups were significantly less than the chow-fed
      animals, indicating increased membrane permeability. CONCLUSIONS: Loss of
      intestinal barrier function plays a major role in nutritionally induced bacterial
      translocation, and the loss of mucosal barrier function to both E. coli and
      phenol red appeared greater in the IV-TPN than the elemental diet-fed rats.

PMID- 7717787
TI  - Gastroesophageal reflux disease and asthma. Diagnosis and management.
AB  - Gastroesophageal reflux is common among asthmatics. It not only may worsen during
      an episode of airways obstruction but also may serve as a trigger for such an
      attack. Both animal and clinical data suggest that gastroesophageal reflux serves
      as a trigger of bronchospasm, potentiates the bronchomotor response to additional
      triggers, or both. Patients with reflux-associated asthma may manifest symptoms
      of gastroesophageal reflux, either classic or atypical, but approximately 25% to
      30% have clinically silent reflux. Despite the use of inadequate doses of acid
      suppressive medicines, clinical trials have documented improvement in respiratory
      symptoms among asthmatics following the treatment of reflux. Recent trials
      suggest long-term improvement in respiratory symptoms following antireflux
      surgery. Selected patients with asthma should be evaluated for gastroesophageal
      reflux. If it is present, such patients may benefit from aggressive antireflux
      therapy.

PMID- 7717785
TI  - Alveolar hydatid disease. Review of the surgical experience in 42 cases of active
      disease among Alaskan Eskimos.
AB  - OBJECTIVE: The authors reviewed the pathophysiology and clinical management of
      endemic alveolar hydatid disease in Alaskan Eskimos, incorporating recent
      developments in diagnosis and treatment. SUMMARY BACKGROUND DATA: Alveolar
      hydatid disease is a highly lethal zoonotic infection caused by the larval stage
      of Echinococcus multilocularis. This cestode is restricted geographically to
      northern climates, where foxes and small rodents represent the natural hosts.
      Domestic dogs also may serve as definitive hosts, and thus, transmit the parasite
      to humans. Human infection is characterized by the development of a cancer-like
      hepatic mass, which may extend to adjacent structures or metastasize to distant
      sites. If the infection goes untreated, mortality reaches 80%. METHODS: The
      medical records of all patients with alveolar hydatid disease diagnosed or
      treated at the Alaska Native Medical Center between 1951 and 1993 were reviewed.
      Forty-two cases of active disease are presented. RESULTS: Nine patients underwent
      resection of hepatic lesions with intent to cure, and each had a favorable
      result. Average post-diagnosis survival of those patients was 22 years; six still
      are living and free of disease. Partial resections or drainage procedures were
      performed in ten patients. Chemotherapy was used to augment the surgical
      treatment of eight patients, and four received chemotherapy alone, resulting in
      improved outcomes compared with historic controls. Late complications included
      hepatic abscess, biliary obstruction, and portal venous hypertension.
      CONCLUSIONS: Whereas alveolar hydatid disease rarely is encountered in other
      areas of North America, the biologic potential for spread of the disease may be
      increasing because of illegal importation of infected foxes to the Eastern
      seaboard. Therefore, the surgical community should maintain an awareness of the
      diagnosis and management of this potentially devastating parasitic infection.

PMID- 7717788
TI  - Angiodysplasia and lower gastrointestinal tract bleeding in elderly patients.
AB  - Angiodysplasia of the colon is one of the most common causes of major lower
      intestinal tract bleeding in the elderly; it occurs predominantly in the cecum
      and on the right side of the colon and is thought to result from degenerative
      changes associated with aging. The clinical presentation is varied, ranging from
      hematochezia or melena to iron-deficiency anemia resulting from long-term blood
      loss. Accurate diagnosis may require a combination of diagnostic techniques, such
      as angiography, nuclear scanning, and colonoscopy. The management plan should be
      individualized for each patient depending on severity, rate of rebleeding, and
      issues of comorbidity. Although conservative medical management is a reasonable
      option for many patients, endoscopic treatment has generally replaced surgery as
      the first line of definitive treatment for angiodysplasias in most of these
      patients. The risk of rebleeding is a considerable problem, and surgical therapy
      yields better results in this aspect. The role of hormonal therapy is not clearly
      established.

PMID- 7717789
TI  - On-site catheterization laboratory and prognosis after acute myocardial
      infarction. Israeli Thrombolytic Survey Group.
AB  - BACKGROUND: Since the introduction of thrombolytic therapy for patients with
      acute myocardial infarction, the use of coronary angiography has substantially
      increased. We sought to determine whether the presence of on-site coronary
      angiographic facilities influenced the utilization of coronary procedures in
      patients with acute myocardial infarction hospitalized in Israel's coronary care
      units. METHODS: A prospective survey was conducted in January and February 1992
      in the 25 coronary care units operating in Israel, 15 of which had on-site
      catheterization facilities. Data on demographics, clinical features, thrombolytic
      therapy, and the type of coronary diagnostic or therapeutic procedures performed
      during the current in-hospital stay were recorded. Mortality, both in-hospital
      and 1 year after discharge, was assessed for all patients in the survey. RESULTS:
      One thousand fourteen consecutive patients with acute myocardial infarction were
      hospitalized during the survey, 307 (30%) of whom were admitted to 10 coronary
      care units without and 707 of whom were treated in hospitals with on-site
      coronary angiography facilities. Demographic and baseline characteristics were
      similar in both groups. Thrombolytic therapy was provided equally (46%) to
      patients admitted to hospital with and without catheterization laboratories.
      Patients admitted to hospitals with these laboratories underwent coronary
      angiography (26%) and percutaneous transluminal angioplasty and/or coronary
      artery bypass grafting (12%) in greater numbers than counterparts admitted to
      hospitals without such laboratories (10% and 5%, respectively). Hospital and
      cumulative 1-year mortality rates were 11% and 18%, respectively, in patients
      admitted to hospitals with on-site catheterization facilities vs 10% and 17%,
      respectively, in the patient group admitted to the other hospitals. Patients
      receiving thrombolytic therapy had similar hospital mortality rates unrelated to
      the availability of coronary catheterization laboratories. CONCLUSION: This
      national survey showed that the availability of invasive coronary facilities led
      to increased use of diagnostic and therapeutic coronary procedures among patients
      with acute myocardial infarction. There was no difference in hospital or 1-year
      mortality rates in patients admitted to hospitals with or without on-site
      coronary angiographic facilities.

PMID- 7717790
TI  - Changes in survival over time after a first episode of Pneumocystis carinii
      pneumonia for European patients with acquired immunodeficiency syndrome.
      Multicentre Study Group on AIDS in Europe.
AB  - BACKGROUND: Factors associated with improved survival over time for patients with
      the acquired immunodeficiency syndrome (AIDS) who have Pneumocystis carinii
      pneumonia at diagnosis are not clearly defined. METHODS: An inception cohort of
      2533 patients with AIDS, diagnosed from 1979 to 1989, from 52 centers in 17
      European countries was studied. Survival 3 months and 3 years after diagnosis was
      estimated by Kaplan-Meier life tables. Independent predictors of survival were
      analyzed by construction of Cox proportional hazards models. RESULTS: Patients in
      whom AIDS and P carinii pneumonia had been diagnosed before 1988 had a poorer 3
      month (ie, short-term) survival, whereas the survival 1 and 2 years after P
      carinii pneumonia was lower only for patients whose disease was diagnosed before
      1987 compared with those with more recent diagnoses. Other variables associated
      with poorer outcome were greater age, infection via blood transfusion, diagnosis
      made in south Europe, and coexisting illnesses. After controlling for these
      prognostic markers in multivariate analysis, improvement in survival over time
      was still evident. For patients who survived the P carinii pneumonia episode,
      both zidovudine and secondary prophylaxis for P carinii pneumonia initiated
      around the time of diagnosis were associated with improved survival, and, after
      controlling for these treatment variables, no statistically significant
      improvement in survival over time was observed. CONCLUSIONS: Survival after an
      episode of P carinii pneumonia has improved within recent years. Increased
      awareness of early symptoms of P carinii pneumonia and better treatment of the
      pneumonia may have led to improvement in short-term survival over time, whereas
      the introduction of zidovudine and increased use of secondary P carinii pneumonia
      prophylaxis may have resulted in the recent increase in survival 1 and 2 years
      after the diagnosis. However, 3-year survival remained unchanged over time,
      implying that the underlying human immunodeficiency virus infection and other
      complications are not effectively controlled.

PMID- 7717791
TI  - Trends in pharmacologic management of hypertension in the United States.
AB  - BACKGROUND: Two new classes of antihypertensive agents were introduced in the
      1980s, but their effectiveness in preventing heart disease and stroke has not
      been demonstrated. Lack of evidence of their efficacy might reasonably be
      expected to discourage their widespread use in management of hypertension.
      METHODS: Use of various classes of antihypertensive agents was estimated from
      published drug use information in an effort to estimate trends in
      antihypertensive drug use and evaluate the impact of these trends on costs of
      antihypertensive therapy in the United States. RESULTS: Proportionate use of the
      five major antihypertensive drug classes shifted markedly between 1982 and 1993.
      Diuretics accounted for 56% of all hypertensive drug mentions in 1982 but only
      27% in 1993, a relative decline of 52%. Use of beta-blockers and central agents
      also declined during this period. Proportionate use of calcium antagonists showed
      the greatest gains, increasing from 0.3% to 27%, while the use of angiotensin
      converting enzyme inhibitors increased from 0.8% to 24%. Given the higher costs
      of the newer agents, and assuming an estimated total cost of antihypertensive
      medications in 1992 of $7 billion, approximately $3.1 billion would have been
      saved had 1982 prescribing practices remained in effect in 1992. CONCLUSIONS: Use
      of calcium antagonists and angiotensin-converting enzyme inhibitors in
      hypertension has increased dramatically in the past 10 years. Without convincing
      evidence of the advantages of these agents, it is difficult to explain the
      continued decline in the use of less expensive agents, such as diuretics and beta
      blockers, which are the only antihypertensive agents proved to reduce stroke and
      coronary disease in hypertensive patients.

PMID- 7717792
TI  - Nondrug treatment trials in psychophysiologic insomnia.
AB  - BACKGROUND: Due to a variety of potential problems with long-term hypnotic use,
      patients and treating physicians often try to avoid drugs in the treatment of
      psychophysiologic insomnia and to use nondrug treatment strategies, but these
      treatments must bring relief within a limited amount of time to be acceptable to
      patients. METHOD: Thirty patients participated in the study. All had, for a
      minimum of 6 months, the complaint of less than 6 hours total sleep time per
      night in conjunction with either: (1) spending more than 30 minutes in bed before
      falling asleep, or (2) awakening during the night within 2 hours of sleep onset
      with difficulty returning to sleep. All subjects had the associated complaint of
      daytime impairment and none had used hypnotics for at least 3 months. Patients
      were randomly assigned to three parallel treatment groups: structured sleep
      hygiene, structured sleep hygiene with late afternoon moderate exercise, and
      structured sleep hygiene with early morning light therapy. Patients responded to
      questionnaires and filled out sleep logs. In addition, they underwent clinical
      evaluation, structured interviews, nocturnal monitoring, and actigraphy. The
      analyzed variables before and at the end of treatment were those derived from
      sleep logs and actigraphy. RESULTS: All subjects showed a trend toward
      improvement, independent of the treatment received, but only the "structured
      sleep hygiene with light treatment" showed statistically significant improvement
      at the end of the trial. CONCLUSIONS: Patients with chronic psychophysiologic
      insomnia may benefit from a nondrug treatment approach. Light therapy appears
      particularly promising.

PMID- 7717793
TI  - Prolonged use of methotrexate for sarcoidosis.
AB  - BACKGROUND: To determine the safety and efficacy of methotrexate as a steroid
      sparing agent in patients with symptomatic sarcoidosis, a nonrandomized
      interventional study of patients with chronic sarcoidosis treated with
      methotrexate for at least 2 years was performed. Efficacy was assessed for all
      patients after 2 years of treatment. Toxicity was assessed for all patients
      receiving therapy for the entire time (a total of 150 patient-years). METHODS:
      Patients were treated in a subspecialty ambulatory clinic at a university
      hospital. Patients with biopsy-confirmed sarcoidosis who had persistent symptoms
      and who were eager to avoid or reduce corticosteroid therapy were selected for
      study. A total of 50 patients completed at least 2 years of methotrexate therapy.
      Patients were treated with oral methotrexate once a week. Dosage was adjusted
      based on the patient's white blood cell count. Clinical response was measured in
      the affected organ, including the lung (measurement of vital capacity), skin
      (regression of skin lesions), and central nervous system (magnetic resonance
      imaging). Also noted was the initial and subsequent dosage of prednisone used as
      therapy for sarcoidosis. RESULTS: Improvement in vital capacity or other affected
      symptomatic organ was noted in 33 of 50 treated patients. Corticosteroids were
      discontinued in an additional six patients who remained stable with clinical or
      symptomatic improvement. The major toxic effects noted in 150 patient-years of
      therapy were hepatic (six patients), leukopenia requiring hospitalization (one
      patient), and cough (one patient). Forty-one liver biopsy procedures were
      performed in 33 patients. Of these, six demonstrated significant changes related
      to methotrexate that led to drug discontinuation. CONCLUSION: Methotrexate is a
      well-tolerated therapeutic agent with significant steroid sparing and efficacy
      for the treatment of chronic symptomatic sarcoidosis.

PMID- 7717794
TI  - Tuberculosis in health care workers at a hospital with an outbreak of multidrug
      resistant Mycobacterium tuberculosis.
AB  - OBJECTIVE: Investigate reports of tuberculosis in health care workers employed at
      a hospital with an outbreak of multidrug-resistant Mycobacterium tuberculosis.
      DESIGN: Case series of tuberculosis in health care workers, January 1, 1989,
      through May 31, 1992. Antimicrobial susceptibility testing and restriction
      fragment length polymorphism analysis of M tuberculosis isolates. Longitudinal
      analysis of cumulative tuberculin skin test surveillance data. Assessment of
      infection control. The patients consisted of 361 health care workers who had
      either serial tuberculin skin tests or tuberculosis. RESULTS: Six health care
      workers, the largest number linked to one multidrug-resistant tuberculosis
      outbreak, had disease due to M tuberculosis that matched the outbreak strain from
      hospitalized patients. The two who were seropositive for human immunodeficiency
      virus died, one of tuberculous meningitis and the other of multiple causes
      including tuberculosis. The estimated risk of a skin test conversion was
      positively associated with time and increased by a factor of 8.3 (1979 to 1992).
      In 1992 the annual risk for workers in the lowest exposure occupational group was
      2.4%. In comparison, nurses and housekeepers had relative risks of 8.0 (95%
      confidence interval, 3.2 to 20.3) and 9.4 (95% confidence interval, 2.7 to 32.3),
      respectively. Laboratory workers had a relative risk of 4.2 (95% confidence
      interval, 1.1 to 15.5). Tuberculosis admissions increased, but the hospital had
      inadequate ventilation to isolate tuberculosis patients effectively. There were
      lapses in infection control practices. CONCLUSIONS: Health care workers who were
      exposed during a hospital outbreak of multidrug-resistant tuberculosis had
      occupationally acquired active disease. The human immunodeficiency virus-infected
      health care workers with tuberculosis had severe disease and died. The risk of
      skin test conversion increased during the study period, and higher exposure
      occupations had elevated risk. Effective infection control is essential to
      prevent the transmission of tuberculosis to health care workers.

PMID- 7717795
TI  - Imported malaria. Clinical presentation and examination of symptomatic travelers.
AB  - BACKGROUND: The diagnosis of malaria in nonendemic countries presents a
      continuing challenge. Increasing physician awareness of the variability in its
      clinical presentation will improve clinical management and health outcomes.
      METHODS: Charts of patients in whom malaria was diagnosed at two hospital-based
      tropical disease centers between September 1, 1980, and December 31, 1991, were
      reviewed. RESULTS: Of a total of 482 cases, 182 were caused by Plasmodium
      falciparum and 246 by Plasmodium vivax. Fifty-two patients with P falciparum
      malaria were hospitalized; 13 were classified as having severe falciparum
      malaria. Nineteen patients with P vivax malaria required hospitalization. The
      only death was caused by P vivax. Chemoprophylaxis was used by, or prescribed
      for, 46% of patients; however, of these, only half were compliant in taking their
      medication. Eighty-seven percent of patients with falciparum malaria presented
      within 6 weeks of return from travel to an endemic area. One third of patients
      with P vivax malaria presented more than 6 months after travel. The average time
      between onset of symptoms and physician contact was 6.7 days. Diagnosis was often
      delayed in those who sought care outside the referral center. Almost all patients
      had a history of fever, but only half were febrile at presentation. Presenting
      symptoms and signs were non-specific. Fifty percent of patients were
      thrombocytopenic. Other laboratory abnormalities were mild. CONCLUSIONS: Since
      the presentation of malaria is vague and nonspecific, the diagnosis should be
      considered in any appropriately symptomatic patient with a history of travel to a
      malaria-endemic area, and appropriate testing should be done. Up-to-date
      information on chemoprophylaxis should be provided to all travelers to malaria
      endemic regions.

PMID- 7717796
TI  - Idiopathic anaphylaxis. An attempt to estimate the incidence in the United
      States.
AB  - BACKGROUND: Idiopathic anaphylaxis has been described and classified, and
      increasing numbers of cases are being seen in the United States and abroad.
      Treatment regimens have been shown to be effective in prophylactic management.
      There is no available information about the number of cases in the United States.
      METHODS: We attempted to determine the number of cases of idiopathic anaphylaxis
      in the United States by mailing a questionnaire to all graduates (for the last 31
      years) of the Northwestern University Allergy-Immunology Fellowship training
      program. RESULTS: Response to the questionnaire was 100%, and 633 cases were
      reported by this survey of 75 allergists. The current total number of identified
      cases of idiopathic anaphylaxis from all reports of cases in the United States is
      1020. CONCLUSIONS: By extrapolation of the cases of idiopathic anaphylaxis
      reported by the allergists surveyed to the approximately 4000 allergists in the
      United States, the estimated number of cases in the United States is between
      20,592 and 47,024. Idiopathic anaphylaxis is potentially fatal, represents a
      source of major medical health care costs, causes anxiety to patients and
      families, occurs in pediatric and adult populations, and is controlled by
      appropriate regimens. The estimated number of cases emphasizes the need for
      careful attention to idiopathic anaphylaxis by physicians.

PMID- 7717797
TI  - Pneumocystis carinii pneumonia during immunosuppressive therapy for
      antineutrophil cytoplasmic autoantibody-positive vasculitis.
AB  - We describe two human immunodeficiency virus-negative patients who developed
      Pneumocystis carinii pneumonia (PCP) during immunosuppressive therapy for
      antineutrophil cytoplasmic autoantibody-positive vasculitis and review the
      literature regarding the pathogenesis and frequency of PCP. The recent
      application of DNA amplification techniques suggests that PCP developing in
      immunocompromised individuals does not necessarily result from reactivation of a
      dormant focus, but may arise as de novo infection after exposure to an exogenous
      source of P carinii. In addition, several reports about clusters of PCP cases
      raise concern about the risk of a nosocomial transmission of P carinii.
      Therefore, PCP should be added to the list of bronchopulmonary complications in
      patients with antineutrophil cytoplasmic autoantibody-positive vasculitis who are
      receiving long-term steroid therapy.

PMID- 7717798
TI  - Heparin dosing protocol.

PMID- 7717799
TI  - Death of a young woman suffering from primary pulmonary hypertension during
      inhaled nitric oxide therapy.

PMID- 7717800
TI  - [Effect of different starch and dietary fiber of preparations levels on immediate
      and subsequent consumption in preschool children 24-48 months of age].
AB  - The aim of this study was to examine in preschool children the effects of
      different levels of starch and dietary fiber of a meal time on the immediate food
      and energy intake (in the same meal time) and in the following meal (subsequent
      intake). The study was performed in 50 children both genders, with ages ranging
      from 24 to 48 months, with normal nutritional status (weight/height index)
      according to the NCHS standards. The food intake was determined by differential
      weighing and energy intake was calculated from proximal analysis. In the lunch,
      several meals were offered differing in their starch and dietary fiber but with
      similar energy density (1 kcal/g). The results of the immediate consumption
      demonstrated that the two dietary treatments were significantly and the effect
      was a lower consumption of food and energy, while the starch an dietary lower
      consumption of food and energy, while the starch an dietary fiber levels
      increased. It was observed and interaction between both variables. The subsequent
      food and energy intake showed the same tendency that was observed in the
      immediate consumption but there was not an interaction between both variables.
      The lowest value of intake was showed by the children who consumed the meal with
      the highest level of starch and dietary fiber. When results of both meal times
      were combined, the same effects were demonstrated. The findings described have
      been not reported by others authors. A probable explanation for these results are
      the lower gastric emptying caused bu high levels of starch and dietary fiber and
      in the specific case of starch by its glycemic index.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7717801
TI  - Effect of addition of brewer's yeast to soy protein and casein on plasma
      cholesterol levels of rabbits.
AB  - The purpose of this study was to determine whether the addition of high levels of
      yeast to casein and soy diets could modify the well known effects of any of these
      proteins on plasma cholesterol. Rabbits, were fed either a diet containing
      soybean protein-brewer's yeast or casein-brewer's yeast (each protein source
      providing 50 percent of the dietary nitrogen content) and casein and soybean
      protein basal diets. Brewer's yeast was obtained from a local beer factory in its
      non-debittered form. The diets contained 20 percent protein, 9 percent coconut
      oil and 1 percent corn oil, with no added cholesterol. After a 22 day
      experimental period, rabbits fed casein developed hypercholesterolemia whereas
      those fed the soybean protein diet did not. The replacement of 50 percent of the
      soy nitrogen by brewer's yeast nitrogen, increased the total cholesterol plasma
      level, but significant differences were only observed between rabbits fed casein
      and casein-yeast and those fed soybean protein. No differences in high density
      lipoprotein cholesterol could be detected among the groups. However, the HDL
      cholesterol/total cholesterol ratio was significantly reduced in response to soy
      substitution by brewer's yeast. The (low density lipoprotein + very low density
      lipoprotein)--cholesterol was increased in all groups with the exception of the
      animals fed purely soy protein. These data suggest a hypercholesterolemic
      activity of the dietary non-debittered brewer's yeast. Nevertheless, according to
      the amino acid composition, the factor responsible for the reported effects of
      dietary yeast was not associated with a high lysine to arginine ratio which could
      be due to extracellular components.

PMID- 7717802
TI  - [Cassava evaluation as a non conventional resource for food industry].
AB  - Mean results of the chemical composition of cassava cultivated in the different
      regions of Mexico are presented and the most important ingredient is starch which
      permits that this natural resource is employed as a no-conventional ingredient in
      food industry, for dextrins, glucose and fructose syrups production. Cassava
      starch is used for baby foods, salsa and mayonnaise manufacture. Because of its
      physico-chemical properties, modified starches are employed in bakery for pies,
      refills and frozen foodstuffs production and have been considered as stabilizers,
      yielding a final product which is maintained fresh and of excellent texture.

PMID- 7717803
TI  - Functional properties of sunflower seed meal obtained by ethanol extraction.
AB  - The objective of this work was to determine the functional properties of
      sunflower seed meal var. Anhandy obtained through ethanol intermittent oil
      extraction in four concentrations (99 degrees GL, 96 degrees GL, 93 degrees GL
      and 90 degrees GL). Meal nitrogen solubility and dispersibility, and oil
      absorption capacities were evaluated. The highest protein solubility (70%) was
      obtained in 93 degrees GL extraction meal. 99 degrees GL and 90 degrees GL
      extracted meals showed the best water absorption performances (11.4 ml H2O/g
      protein), while 96 degrees GL meal was the best in oil absorption (7.3 ml free
      oil absorbed/g protein). The highest nitrogen dispersibility was found in 96
      degrees GL and 99 degrees GL meals (1.6% dispersed nitrogen or ca. 27% yield).
      Nitrogen solubility essays in salt solutions indicated that pH 11 was the best;
      however, the yield was even lower than in aqueous solutions. Meals obtained with
      more concentrated ethanol-water solutions were indicated for further processing
      to concentrates and isolates.

PMID- 7717804
TI  - Sunflower seed protein concentrates and isolates obtention from ethanol oil
      extraction meals--(technical note).
AB  - The objective of this work was to study and identify the necessary processing
      steps for obtaining good quality sunflower seed protein concentrate and isolate
      when the oil is extracted with ethanol. This work is part of a research project
      on using ethanol as renewable solvent for sunflower seed oil recovery and
      possible further processing of the meal. Both 99 degrees GL and 90 degrees GL
      ethanol were employed in the extractions to produce the concentrate. Isolates
      were obtained by treating the concentrate with NaOH and HCl solutions and final
      rinsing with acidified water. Both products were light in color and almost free
      from chlorogenic acid.

PMID- 7717805
TI  - [Cereal bars with peanut and puffed amaranthus: chemical composition and
      stability in accelerated storage].
AB  - Three different cereal bars, CM3A-CM3B and CM3C were prepared following the flow
      sheat of Escobar et al: different amount of oat, wheat germ, and puffed
      amaranthus were used: to stick them together, natural sweeteners and fats were
      added. Proximate analysis, were run on raw materials and snack bars. They were
      evaluated organoleptically to know their quality and acceptability. Bars were
      kept in accelerated storage at 37 degrees C during 15 days to know their
      stability. Every 5 days were measured the water activity (Aw), moisture, and
      peroxides development; also appearance of organoleptic randicity. Acceptability
      of bar CM3B was 91.67% with 0.0% of rejection; CM3A and CM3C got the same
      acceptability (66.67%) and 8.33% of rejection. In accelerate storage, Aw and
      moisture content decreased until reaching a value of 0.48 and 5.9 in the CM3B
      bar, respectively. Peroxide content of CM3B and CM3C increased gradually up to 12
      and 17 meq/kg respectively at 15 days. Rancyd aroma appearance was not the same
      in the bars, CM3A and CM3B had a decreasing at 15 days, while CM3C showed an
      increasing at the same time. In brief, CM3B showed the best sensory quality, the
      higher acceptability and the greater stability in accelerated storage.

PMID- 7717806
TI  - [Effect of ripening and drying on pro-vitamin A carotenoid content in pepper
      (Capsicum annuum var. Anaheim)].
AB  - The content of the principal carotenes with biological activity (alpha-, beta,
      gamma-carotene and beta-criptoxantine) in green pepper (Capsicum annuum var.
      Anaheim) was determined in order to investigate the vitamin A content during the
      traditional process of ripening and drying. The analytical technique used was
      high pressure liquid chromatography (HPLC) with a Novapack C18 column and
      acetonitrile/methanol/tetrahydrofuran (58V:35V:7V) as a mobile phase. The results
      showed differences in vitamin A activity of 7.2 +/- 0.8, 51.1 +/- 2.4 and 55.3 +/
      1.2 micrograms of RE/g dry matter for immature, mature and dry pepper fruit
      respectively (p < 0.05). Approximately 95% of total activity was due to beta
      carotene being synthesized faster than the other carotenes under study during the
      ripening process. Total vitamin A activity reached its highest value at 14 days
      after harvest (2738.8 +/- 128.6 micrograms RE/100 g of edible portion), with a
      decrease in activity with time.

PMID- 7717807
TI  - [Classification of commercial Venezuelan honey].
AB  - Commercial honeys were analysed to study their quality in the Venezuelan market
      and were grouped in progressive classes according to their organoleptical and
      physico-chemical characteristics. For that purpose, 500 honey samples were
      collected in 1985-1987 in different locations of Venezuela. By sensorial
      evaluation, 13.4% of the samples were recognized as honey frauds and 86.6% as
      genuine honey. The analytical results were compared with the standards
      established in the Venezuelan regulation for honey (COVENIN 2191-84), and 59.8%
      of the genuine honeys were found to be altered because they failed to fulfil the
      requirement for moisture content (39.8%), reducing sugars (11.2%), sucrose
      (17.4%), ash (31.7%), total acidity (25.5%), hydroximethylfurfural (43.2%) and
      diastase (34.0%). Honey frauds never fulfilled the requirements for
      hydroximethylfurfural and diastase. The high values found for acidity and ash
      content in genuine honeys with only one altered characteristic, reveal the need
      to review the established requirements in the national regulation for honey. It
      is suggested to use the nitrogen content of honey to detect honey frauds in
      Venezuela.

PMID- 7717808
TI  - [Chemical and nutritional characterization of amaranthus (Amaranthus cruentus)].
AB  - Two samples of Amaranthus cruentus harvested in 1987 (sample A) and 1990 (sample
      B) were studied. Whole and refined flours were obtained. The whole flours
      contained 14.6 and 12.6% protein and 6.6 and 7.3 ether extraction, respectively.
      Both samples contained significant levels of Ca, P, Mg and K. Amaranth oil
      contained 19% palmitic acid, 3.4% stearic acid, 3.4% stearic acid, 34% oleic acid
      and 33% linoleic acid. Docosaenoic acid (C22:1) was present at the level of 9%.
      The ratio of saturated to unsaturated fatty acids was approximately 1:3. The
      level of crude fiber was 3.7% in the whole flours and 2.4% in the refined ones.
      Biological protein quality of flours was measured in the rat by the net protein
      ratio (NPR) method. The NPR values of the four materials tested ranged from 3.04
      to 3.20 (NS), as compared with 4.08 for casein. These values are equivalent to 75
      78% of the standard protein. Blends of raw wheat flour and whole amaranth flour
      fed to rats produced a good complementary effect between proteins, as shown by
      PER test. Wheat flour gave a poor PER value of 0.54. However, this figure
      increased with every increment of amaranth flour reaching a value of 2.15 for the
      blend 25:75. The PER for the amaranth diet (0:100) was 1.94 (casein 2.77). As
      expected, the extrusion process applied to the wheat/amaranth and corn/amaranth
      mixtures improved the biological quality of the protein. The wheat flour diet
      (100:0) gave a PER value of 1.64. Mixture 90:10 produced a low non significant
      increase in the protein quality.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717809
TI  - Lactose vs. lactose free regimen in children with acute diarrhoea: a randomized
      controlled trial.
AB  - OBJECTIVE: To determine whether the routine use of a lactose free formula (AL
      110, Nestle Labs.) in hospitalized children aged one to 24 months reduces the
      duration of acute diarrhea (AD). METHODS: After being stratified according to age
      and nutritional state, 28 and 24 patients were randomly allocated to receive AL
      110 or lactose formula, respectively. The main outcome was the duration of
      diarrhoea after refeeding, both in hours and days. Secondary outcomes were
      evaluated by blind observers. Results were compared using t test, the Mann
      Whitney test and Chi square. RESULTS: No differences were found between the diets
      without and with lactose regarding duration of diarrhoea in hours (mean, 41.9 h
      vs 54.4 h; p = 0.247) or days (median, 0 d vs 0 d; p = 0.717), the percentage of
      failures (3.6% vs 8.3; p = 0.2), and the mean weight increment (0.78 kg vs. 0.82
      kg; p = 0.788). The study power to find a 50% (27h) reduction of AD duration was
      71%. CONCLUSION: Although the power of this trial was slightly below that
      previously fixed (80%), the results suggest that routine use of lactose free
      formula does not reduce the duration of AD in hospitalized children.

PMID- 7717810
TI  - Noninvasive long-term ventilatory support for individuals with spinal muscular
      atrophy and functional bulbar musculature.
AB  - Ten individuals with spinal muscular atrophy (SMA) and chronic ventilatory
      insufficiency were trained in the use of assisted coughing techniques and
      received intermittent positive pressure ventilation (IPPV) via oral and/or nasal
      interfaces for a mean of 5.3 (range = 1 to 17) years. During this time they had
      significantly fewer respiratory complications than before introduction of
      noninvasive respiratory muscle aids despite the fact that 6 of the 10 went on to
      require more than 20 hours per day of ventilator use with less than 2 hours of
      ventilator-free breathing time (VFBT). All except two noninvasive IPPV users had
      vital capacities (VCs) less than 13% of predicted normal. They could, however,
      communicate verbally and take nutrition by mouth. All of the patients remained in
      the community. Five patients were gainfully employed and four were in school. We
      conclude that noninvasive respiratory muscle aids including noninvasive IPPV and
      assisted coughing techniques are effective and practical alternatives to
      tracheostomy for SMA patients with ventilatory failure but functional bulbar
      musculature.

PMID- 7717811
TI  - Postural aberrations in low back pain.
AB  - The purpose of this study was to measure and describe postural aberrations in
      chronic and acute low back pain in search of predictors of low back pain. The
      sample included 59 subjects recruited to the following three groups: chronic,
      acute, or no low back pain. Diagnoses included disc disease, mechanical back
      pain, and osteoarthritis. Lumbar lordosis, thoracic kyphosis, head position,
      shoulder position, shoulder height, pelvic tilt, and leg length were measured
      using a photographic technique. In standing, chronic pain patients exhibited an
      increased lumbar lordosis compared with controls (p < .05). Acute patients had an
      increased thoracic kyphosis and a forward head position compared with controls (p
      < .05). In sitting, acute patients had an increased thoracic kyphosis compared
      with controls (p < .05). These postural parameters identified discrete postural
      profiles but had moderate value as predictors of low back pain. Therefore other
      unidentified factors are also important in the prediction of low back pain.

PMID- 7717813
TI  - Sports medicine in physical medicine and rehabilitation residency programs.
AB  - Because sports medicine is a rapidly expanding field within many specialties, it
      is important to gauge how active physiatrists have become in this arena. A
      nationwide survey of program directors and chief residents of physical medicine
      and rehabilitation residency programs was conducted to determine such prevalence.
      For the purposes of this study, sports medicine was defined as the routine care
      of athletes involved in organized sporting activities at any level of
      competition. Questionnaires were mailed to program directors and chief residents
      with response rates of 79.7% each. Overall, correlation of the answers between
      groups was high. The level of interest of residents was rated at 46%. Data was
      also obtained regarding research, clinical rotations, lectures, fellowships,
      association with academic departments of other specialties, and affiliations with
      professional sports medicine organizations. The actual level of educational
      opportunities available was much lower than might be expected given the high
      level of interest expressed. It is reasonable to conclude that more opportunities
      should exist for education in sports medicine.

PMID- 7717812
TI  - Electromyographic analysis of four techniques for isometric trunk muscle
      exercises.
AB  - Posture to avoid hyperextension of the lumbar spine during isometric trunk muscle
      exercises has been widely recommended. However, there are no common standards for
      cervical and pelvic alignment during exercises. To investigate the effects of
      four different techniques regarding cervical and pelvic alignment,
      electromyographic (EMG) and radiological studies were performed on 30 healthy
      subjects. The four different postures were: (1) maximally extended neck, (2)
      neutral neck, (3) maximally flexed neck, and (4) maximally flexed neck with
      pelvic stabilization through muscle contraction. During flexion exercises, the
      largest increase in EMG activity in the abdominal muscles was observed with the
      flexed neck with pelvic stabilization (p < .01). During extensor exercises, the
      largest increase in EMG activity in the erector spinae was also obtained in the
      same position (p < .01). An increase of EMG activity in antagonist muscles (eg,
      erector spinae on flexion, and rectus and oblique muscles on extension) was also
      greatest with the flexed neck and pelvic stabilization. From the radiographic
      study, degrees of lumbar lordosis were least with the flexed neck and pelvic
      stabilization (p < .01). This study showed that neck and pelvic alignment can
      influence the EMG activity of trunk flexors and extensors during isometric trunk
      exercises. For isometric trunk muscle exercises, a maximum flexed neck with
      pelvic stabilization through muscle contraction seems to be the most optimal
      posture for decreasing the lumbar lordosis and for activating trunk flexors and
      extensors most effectively.

PMID- 7717814
TI  - Relation between grip strength and radial bone mineral density in young athletes.
AB  - In this study, we evaluated the relationship between bone mineral density (BMD)
      and muscle strength in young athletes who had not yet experienced age-related
      bone loss. Radial BMD and grip strength were measured in 10 male college
      wrestlers, 16 female college basketball players, and 12 female college tennis
      players. Radial BMD was measured in the distal and middle radius by dual energy x
      ray absorptiometry (DEXA). Isometric grip strength was assessed with a hand-held
      dynamometer. The dominant forearm was examined in the amateur wrestlers and
      basketball players for grip strength and BMD. Both forearms were examined in the
      tennis players. A significant positive correlation was found between radial BMD
      and grip strength in the dominant forearm, and between radial BMD and body
      weight. Moreover, to eliminate a possible effect of body weight on radial BMD, we
      compared radial BMD with grip strength in both the dominant and nondominant arm
      of 12 college tennis players. Grip strength in the dominant forearm was
      significantly greater than in the nondominant forearm. The midradial BMD of the
      dominant forearm was also significantly higher than in the nondominant forearm.
      Based on these findings, we conclude that grip strength is one of the determinant
      factors of radial BMD in the dominant forearm of young college athletes.

PMID- 7717815
TI  - Shoulder complaints in patients with reflex sympathetic dystrophy of the upper
      extremity.
AB  - Five hundred forty-one patients with reflex sympathetic dystrophy (RSD) of the
      upper extremity were prospectively studied. One hundred fifteen patients
      complained of pain and/or limited range of motion in the shoulder. Shoulder
      complaints more often occurred in women (p = .01); age and etiology were not
      different from patients with RSD without shoulder complaints. Physical
      examination showed a tendinitis of one or both tendons of the biceps muscle in
      109 patients. Seventy one patients were treated with local injection of
      bupivacaine followed by methylprednisolone. This resulted in permanent relief of
      complaints in 34 patients, temporary or moderate relief in 31, no difference in
      3, increase of complaints in 1 patient, and in 2 patients results were not
      documented. We conclude that shoulder complaints in RSD occur in a minority of
      patients and more often in female patients. There are no predisposing factors.
      The pathophysiologic mechanism for developing shoulder complaints remains
      unknown. In most cases complaints can be attributed to a bicipital tendinitis for
      which local injection of bupivacaine followed by prednisolone are both diagnostic
      and therapeutic.

PMID- 7717816
TI  - Skin temperature response to a pressure load: studies in subjects before and
      during spinal anesthesia.
AB  - The Pressure-Temperature-Time method (PTT-method) is a method to investigate skin
      temperature changes in response to a pressure load. This method was used to
      investigate the effect of an acute nerve conduction block on the skin temperature
      increase of the trochanter major, after the pressure load was removed. The PTT
      method was used in a group of 30 subjects, undergoing minor surgical procedures,
      before and during an anesthetic nerve conduction block at L2-L3. In comparison
      with the results before spinal anesthesia, the skin temperature responses were
      significantly delayed (p < .01) and slower (p < .001) after the spinal blockade.
      We concluded, therefore, that the nervous system has an important effect on the
      recovery of skin temperature after a pressure load.

PMID- 7717817
TI  - Relation between needle electromyography and nerve conduction studies in patients
      with carpal tunnel syndrome.
AB  - Four hundred eighty cases of electrodiagnostically confirmed carpal tunnel
      syndrome were reviewed to determine if the findings on nerve conduction studies
      could predict the presence or absence of fibrillation potentials or motor unit
      changes on the needle examination of the abductor pollicis brevis (APB). The
      needle examination is more uncomfortable and the ability to predict the findings
      in this setting from standard nerve conduction studies (NCS) would make the test
      more acceptable to patients. All patients had median and ulnar nerves (both
      sensory and motor) tested, as well as the needle evaluation of the APB. Two
      hundred thirty-one patients had an abnormal needle evaluation as defined by
      presence of one of the following conditions: abnormal spontaneous activity,
      increased motor unit action potential (MUAP) amplitude, or increased MUAP
      polyphasia. One hundred five patients had fibrillation potentials. The mean
      median motor and sensory amplitudes and latencies, as well as age, did differ in
      the normal and abnormal needle examination groups, but the sensitivity for
      predicting an abnormality ranged from 57% to 68%. The ratio of the median to the
      ulnar amplitudes did not improve the sensitivity of predicting the abnormal
      needle findings. Motor and sensory evoked potential latencies were the most
      important predictors of an abnormal needle examination.

PMID- 7717818
TI  - Post-stroke autonomic nervous system function: palmar sympathetic skin responses
      thirty or more days after cerebrovascular accident.
AB  - We studied sympathetic nervous system (SNS) function after cerebrovascular
      accident (CVA) by measuring hypothenar sympathetic skin responses (SSR) to normal
      or hemiplegic arm electrical stimulation. We anticipated SNS function after CVA
      to be asymmetric and selected null hypotheses of bilaterally symmetric SSR
      latencies and amplitudes irrespective of side of stimulation and/or recording.
      Thirteen patients between ages 44 and 77 years (median 59) were tested between 1
      and 72 months (median 15) after CVA. Hypothenar recording and dorsal reference
      surface electrodes were used. Amplifier bandwidth was set from 0.5 to 100 Hz.
      Gain was adjusted to allow adequate recognition of the waveforms. Sweep speed was
      set to 500ms/div. Stimulus width was set to 0.2 ms and intensity was increased
      stepwise from 10mA initially until optimum responses were obtained. Nonparametric
      statistics were used to analyze the data. SSRs were present in all patients on
      both the normal and the hemiplegic sides irrespective of the side of stimulation.
      Median SSR latency recorded homolaterally to the stimulus site was found to be
      80ms shorter than median SSR latency recorded heterolaterally. Median SSR latency
      in left hemiplegics was found to be 16% longer than in right hemiplegics.
      Otherwise, neither side of hemiplegia, side of stimulation, side of recording nor
      any paired combination thereof were found to be significant. Our finding of
      bilaterally obtainable SSRs after CVA diverges from that of Uncini and colleagues
      but presumably only reflects the difference in poststroke chronology between the
      respective samples.

PMID- 7717819
TI  - Physiologic responses of cardiac patients to supine, recumbent, and upright cycle
      ergometry.
AB  - Physiological responses were compared in nine stable male cardiac patients (mean
      +/- standard error (SE): age, 68.3 +/- 8.1 years; height, 172.7 +/- 3.9cm;
      weight, 72.8 +/- 14.5kg) during stationary cycling in the supine, recumbent, and
      upright positions. A discontinuous exercise protocol was performed in which each
      stage included 3 minutes of exercise and 1 minute of recovery. Each subject's
      workload started at 150kgm.min-1 and increased by 150kgm.min-1 per stage until
      volitional fatigue. Testing sessions were randomized and performed 1 week apart.
      Subjects continued their normal medication regimen. All subjects were
      participants in a community-based cardiac rehabilitation program. Dependent
      variables were assessed at two different intensities; submaximal (300kgm.min +/-
      1) and maximal. A two-way repeated measures ANOVA found no significant
      differences in systolic blood pressure (SBP), diastolic blood pressure (DBP),
      minute ventilation (VE), respiratory exchange ratio (R), rate pressure product
      (RPP), and rating of perceived exertion (RPE) at submaximal (300kgm.min +/- 1)
      and maximal exercise efforts. Heart rate (HR) was significantly lower (p < or =
      .05) in the supine position compared with either the upright or recumbent
      positions during the submaximal workload. In addition, oxygen uptake (VO2) was
      significantly lower in the supine position at the submaximal workload (p < or =
      .05) compared with both upright and recumbent. No difference in HR or VO2 was
      observed at maximal exercise. Regressions of HR on VO2 showed similar slopes and
      intercepts for supine, recumbent, and upright ergometry.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7717820
TI  - Short-term exercise training effect after myocardial infarction on myocardial
      oxygen consumption indices and ischemic threshold.
AB  - This study was undertaken to determine whether adaptations to short-term exercise
      training after myocardial infarction, could affect the response of heart rate,
      blood pressure and double product at submaximal workload, and the behavior of
      electrocardiographic ST segment depression. We studied 60 patients (group A) who
      underwent a modest level exercise training for 3 months and 40 patients (group B)
      who did not participate in this program. All these subjects were involved in the
      trial 1 week after discharge from the hospital. Submaximal treadmill stress test
      was performed after the 3-month period. The stress test duration was longer (p <
      .01), heart rate (p < .001), systolic blood pressure (p < .01) and double product
      (p < .01) at submaximal workload were lower and the onset of ST depression of 1
      mm was delayed (p < .01) in group A. In conclusion, postinfarction short-term
      exercise training increases the exercise tolerance, decreases the heart rate,
      systolic blood pressure, and double product response to exercise and improves the
      ischemic threshold.

PMID- 7717821
TI  - Diaphragm and accessory respiratory muscle stimulation using intramuscular
      electrodes.
AB  - We tested the hypothesis that electrical stimulation of respiratory muscles can
      be obtained from intramuscular electrodes. In acute anesthetized dogs, suture
      type intramuscular electrodes were placed in each hemidiaphragm and needle
      electrodes were placed in various intercostal regions of the thorax. During a
      hyperventilation induced period of apnea a 2-second stimulation was applied to
      the diaphragm or to the thoracic electrodes, followed by a combined thoracic
      diaphragm stimulation period. Thoracic expansion and tidal volumes were measured
      as indices of inspiratory effort. We found that diaphragm stimulation produced
      tidal volumes between 104% and 180% of spontaneous breathing. Electrodes in the
      upper thorax produced chest expansion and when combined with diaphragm
      stimulation increased tidal volumes (p < .05). We conclude that intramuscular
      electrodes represent a feasible method for long-term electrogenic ventilation.
      Also, thoracic support for diaphragm pacing in quadriplegics could produce a more
      effective long-term system that is less prone to fatigue and failure.

PMID- 7717822
TI  - Urinary tract infection in persons with spinal cord injury.
AB  - Persons with spinal cord injury (SCI) have an increased risk of developing
      urinary tract infections. Certain structural and physiological factors, such as
      bladder over-distention, vesicoureteral reflux, high-pressure voiding, large post
      void residuals, stones in the urinary tract, and outlet obstruction increase the
      risk of infection. The method of bladder drainage also influences the risk of
      urinary tract infection, and most persons with SCI on indwelling or intermittent
      catheterization develop urinary tract infection. The association of behavioral
      and demographic factors with the risk of urinary tract infection are less well
      understood. The method of specimen collection must be considered when determining
      the significance of bacteria. A national consensus conference sponsored by the
      National Institute on Disability and Rehabilitation Research defined significant
      bacteriuria as: > or = 10(2) colony forming units (cfu) of uropathogens per
      milliliter of urine in catheter specimens from persons on intermittent
      catheterization; > or = 10(4)cfu/mL in clean-voided specimens from catheter-free
      males using condom catheters; and any detectable concentration of uropathogens in
      indwelling catheter or suprapubic aspirate specimens. Symptomatic urinary tract
      infection warrants therapy, but the diagnosis is complicated by the poor
      sensitivity and specificity of symptoms and signs. Pyuria is generally present in
      persons with symptomatic urinary tract infection, although it is a nonspecific
      test, and its absence generally indicates the absence of symptomatic urinary
      tract infection. Treatment of asymptomatic bacteriuria has not been shown to be
      beneficial and increases the risk of development of antimicrobial-resistant
      uropathogens. Antibiotic prophylaxis is generally not recommended because of its
      unproven benefit in several studies and its association with emergence of
      antimicrobial resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717823
TI  - Caloric requirements of a spastic immobile cerebral palsy patient: a case report.
AB  - This article documents the reduced caloric requirements for a spastic, immobile,
      cerebral palsy patient. We report an 11-year-old immobile, spastic, quadriparetic
      patient who remained obese despite receiving less than one half of the
      recommended basal caloric requirements for age. Basal metabolic rate was
      determined by indirect calorimetry using a Sensor Medics 2900 instrument.
      Standard reference sources indicate that an able-bodied 11-year-old child of
      comparable height requires 1,493 kcal/d for support of basal metabolic functions.
      Our patient was followed for 8 weeks on reduced calories and assessed for
      adequacy of diet by nitrogen balance studies and other appropriate parameters.
      Our data suggest that a subset of severely impaired children with cerebral palsy
      may require much less in total kilocalories per day for nutritional support than
      previous studies would indicate.

PMID- 7717824
TI  - Heterotopic ossification: treatment of established bone with radiation therapy.
AB  - Ectopic bone formation or heterotopic ossification (HO) is frequently seen on
      rehabilitation units after total hip arthroplasties, burns, and neurological
      injuries. Currently the major role for treatment is in prophylaxis and the major
      methods include anti-inflammatory medications, irradiation, and diphosphanate
      administration. These prophylactic measures are generally considered to be
      ineffective for the treatment of ectopic bone once it has already formed. We
      describe two cases of HO for which a radiation therapy protocol was used to treat
      established, ectopic bone after it had become problematic. Both patients were
      found to have increased range of motion and decreased complaints of pain after
      treatment, though no gross plain film x-ray changes were noted. We conclude that
      radiation therapy may be useful not only for prophylaxis of heterotopic
      ossification but for ectopic bone after it has been formed, especially when pain
      and progressively decreased range of motion are problematic.

PMID- 7717825
TI  - Ruptured intracranial mycotic aneurysm: a rare cause of intracranial hemorrhage.
AB  - Intracranial mycotic aneurysm is a rare complication in patients with infective
      endocarditis occurring in about 2% to 10% of cases. Although the risk of rupture
      is about 1.7%, it is usually a catastrophic event with a fatality rate of 80%.
      Neurological deficits secondary to cortical involvement are common, given the
      frequency of intralobar hemorrhage. We report two cases of intracerebral
      hemorrhage caused by ruptured intracranial mycotic aneurysms. Both had
      involvement of the right frontoparietal lobes with resultant left hemiparesis,
      left homonymous hemianopia, and impairments of cognition and perceptual function.
      Despite intensive rehabilitation, their functional outcomes were less than
      satisfactory as they needed assistance in self-care activities and mobility on
      discharge.

PMID- 7717826
TI  - Prosthetic fitting and ambulation in a paraplegic patient with an above-knee
      amputation.
AB  - The combination of paraplegia with an above-knee amputation is a complex injury
      that makes the rehabilitation process difficult. This article describes a case of
      T12 paraplegia and an above-knee amputation. After the rehabilitation course, the
      patient achieved full ambulatory independence with an ischial containment,
      contoured adducted trochanteric controlled alignment method (CATCAM) prosthesis
      and a knee ankle foot orthosis (KAFO). Difficulties in fitting a functional
      prosthesis to an insensate limb and the rehabilitation stages leading to
      functional ambulation are reviewed.

PMID- 7717828
TI  - The value of medical rehabilitation.

PMID- 7717827
TI  - Skin complications in SCI.

PMID- 7717830
TI  - Malnutrition in stroke patients on the rehabilitation service and at follow-up:
      prevalence and predictors.
AB  - This prospective study presents the prevalence and risk factors of malnutrition
      in 49 consecutive stroke patients on the rehabilitation (Rehab) service and at 2-
      to 4-month follow-up. Malnutrition was diagnosed using biochemical and
      anthropometric data. Stroke patients, on admission to Rehab, have a very high
      prevalence of malnutrition. Malnutrition, 49% on admission, declined to 34%, 22%,
      and 19% at 1 month, 2 months, and follow-up, respectively. Dysphagia, 47% on
      admission, was associated with malnutrition (p = .032) and significantly declined
      over time. Using logistic regression, predictors of malnutrition on admission
      involved acute service tube feedings (p = .002) and histories of diabetes (p =
      .027) and prior stroke (p = .013). Tube feedings, associated with malnutrition on
      admission (p = .043), were more prevalent in brain stem lesion patients. Patients
      tube fed > or = 1 month during rehabilitation or at home were not malnourished.
      Malnutrition was associated with advanced (> 70 years) age at 1 month (p = .002)
      and weight loss (p = .011) and lack of community care (p = .006) at follow-up.
      Early and ongoing detection and treatment of malnutrition are recommended during
      rehabilitation of stroke patients both on the service and at follow-up.

PMID- 7717829
TI  - Substance abuse as a mediating factor in outcome from traumatic brain injury.
AB  - A review of recent research addressed two questions: how common are problems of
      substance abuse in traumatic brain injury (TBI), and to what extent does alcohol
      and other drug use mediate outcome? Studies showed alcohol intoxication present
      in one third to one half of hospitalizations; data for other drug intoxication
      were not available. Nearly two thirds of rehabilitation patients may have a
      history of substance abuse that preceded their injuries. Intoxication was related
      to acute complications, longer hospital stays, and poorer discharge status;
      however, these relationships may have been caused by colinearity with history.
      History of substance abuse showed the same morbidity, and was further associated
      with higher mortality rates, poorer neuropsychological outcome, and greater
      likelihood of repeat injuries and late deterioration. The effect of history may
      be caused by subgroups with more severe substance abuse problems. Implications
      for rehabilitation are discussed, including the potential negative impact of
      untreated substance abuse on the ability to document efficacy of rehabilitation
      efforts.

PMID- 7717831
TI  - Clinical applicability and test-retest reliability of an external perturbation
      test of balance in stroke subjects.
AB  - We address the test-retest reliability and clinical applicability of an adapted
      external perturbation balance assessment, ie, the Postural Stress Test (PST).
      Repeated-measures were designed to assess the clinical features of a component of
      balance disorder in stroke. Twenty ambulatory stroke patients and 20 age-, gender
      , height-, and weight-matched healthy control subjects participated in this
      study. Stroke patients were tested (using the adapted PST) on 4 separate days;
      matched control subjects were tested on one occasion. With the subject standing,
      backward perturbation forces were applied at the level of the center of gravity.
      Postural reactions to the test were scored in real-time and from videotape, from
      two different viewing angles, ie, 45 degrees and 90 degrees to the saggital
      plane. Scores (out of a maximal of 81) were ascertained using a 10-point
      subjective-observational scale. None of the control subjects fell during testing;
      four of the hemiplegic subjects fell. Subjects were protected from potential
      injury by a custom-designed safety harness system. For the hemiplegic subjects,
      intraclass correlation coefficients (ICCs), calculated as the reliability of any
      one occasion, ranged from 0.71 to 0.77, whereas those calculated as the
      reliability of the mean of the first two occasions ranged from 0.83 to 0.93.
      Although scores on the fourth occasion were significantly greater than those on
      the third occasion, both being significantly greater than those on the first and
      second test occasions (p < .05), differences were less than 5 points on the 81
      point scale.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717832
TI  - Deep vein thrombosis: prevention in stroke patients during rehabilitation.
AB  - Deep vein thrombosis (DVT) and subsequent pulmonary embolism (PE) is a major
      source of mortality and morbidity in stroke patients. This study was designed to
      determine the effectiveness of different prophylactic treatments in the
      prevention of DVT after a stroke in patients undergoing rehabilitation. An
      additional objective was the identification of risk factors for DVT in stroke in
      patients during rehabilitation. Three hundred and sixty patients, over a 3-year
      period, were randomly assigned to one of four groups: adjusted dose heparin,
      intermittent pneumatic compression (IPC), functional electrical stimulation
      (FES), or control. There was no significant difference in the development of DVT
      by treatment group. Patients with DVT on admission (prevalent, n = 61) were
      compared with the study patients (n = 360). Time interval (from stroke to
      admission) and lactic dehydrogenase (LDH) concentration were significant risk
      factors, as well as predictors, for development of DVT (p < .000). These results
      suggest that the longer a patient remains without DVT prophylaxis after a stroke,
      the greater the risk of developing DVT and this supports early prophylaxis before
      rehabilitation.

PMID- 7717833
TI  - Rehabilitation teams decisions on discharge housing for stroke patients.
AB  - For older people who have had a stroke, appropriate housing can promote
      independence and well being. However, suboptimal team accommodation
      recommendations may result in placement of an individual where their needs are
      not met, and their skills are not maximized. Although clinical judgments
      regarding patient discharge are routinely made by rehabilitation teams, this area
      has received limited research attention. This study examines how rehabilitation
      teams determine the most appropriate housing to recommend to stroke patients
      after their discharge from hospitals. A Social Judgment Theory approach was used
      to document and analyze the accommodation recommendations and policies of 13
      rehabilitation teams (clinician n = 74). Teams were asked to consider 50
      hypothetical stroke patients, and determine the most appropriate discharge
      housing to recommend to these patients. Each stroke patient was described in
      terms of 8 attributes: mobility status, ability to manage their own affairs,
      patient's choice of housing, personal activity of daily living (ADL) skills,
      domestic and community ADL skills, general health status, social situation, and
      premorbid living arrangements. Clinicians were provided with a response scale on
      which to record their recommendations. The results showed considerable yet
      reliable differences among teams concerning recommendations made, and judgment
      policies adopted. Although the highly structured and hypothetical nature of this
      research limits the external validity of findings, the results suggest that teams
      may also face difficulties with housing recommendations in the more complex
      clinical environment. Further studies to assess actual clinical team decision
      making are needed. Such studies could lead to the development of a standardized
      research-based protocol to help teams formalize and optimize their housing
      recommendations.

PMID- 7717834
TI  - Outpatient planning for persons with physical disabilities: a randomized
      prospective trial of physiatrist alone versus a multidisciplinary team.
AB  - The purposes of this study were to assess the effect of adding a physiatrist to
      the usual community management of persons with complex disabilities, and to
      determine whether there were differences in decision making and patient outcome
      between evaluations by a physiatrist alone or with a multidisciplinary team in
      this population. Consecutively referred patients with functional complaints in
      two of the following areas, mobility, activities of daily living, emotions and
      cognition, work, or social support, were randomly assigned to a multidisciplinary
      outpatient team evaluation or physiatrist evaluation in an office setting. Forty
      persons, 21 team and 19 office, served as subjects. For the entire group,
      functional assessment scores before and after evaluation were as follows: Barthel
      index 71.79 versus 76.47 (p < .008) and Frenchay Activities index 9.97 versus
      11.32 (p < .05) Wilcoxon Signed Ranks test. Patients quality of life differences
      were significant (p < .03 or less by Wilcoxon). Most differences between team and
      physiatrist were not shown to be statistically significant in this small
      population. Physiatric evaluation, with or without a multidisciplinary team, can
      improve outpatient functional status and quality of life for persons living in
      the community with complex disabilities.

PMID- 7717835
TI  - Criteria for selection of a payment method for inpatient medical rehabilitation.
AB  - This article presents the results of a 3-stage Delphi survey designed to identify
      the policy criteria that should govern the evaluation of alternative payment
      methods and guide the selection of a payment method for inpatient medical
      rehabilitation. The Delphi survey (n = 85) included four groups of participants:
      consumers (n = 8), providers (n = 35), payers (n = 15), and health services
      researchers (n = 27). The Delphi survey uncovered 16 evaluation criteria. Delphi
      participants evaluated each criterion on a 10-point scale (1 = not important; 10
      = greatest importance). Respondents value maximize patient/family outcome,
      maximize access, and maximize efficiency as the three most important criteria.
      Respondents report that minimize financial risk is the least important criterion.
      The results from both stage 2 and stage 3 (response rate = 85%) indicate a high
      level of consensus across the four respondent groups.

PMID- 7717836
TI  - Functional outcomes after inpatient rehabilitation of patients with end-stage
      renal disease.
AB  - There is a paucity of information on functional benefits of inpatient
      rehabilitation of patients with end-stage renal disease (ESRD). This study
      examined admission and discharge Functional Independence Measure (FIM) scores of
      45 ESRD patients admitted over a 33-month span to determine if these patients
      made functional gains similar to 2,324 concurrently admitted general
      rehabilitation patients without ESRD. FIM scores were transformed and reported as
      scaled (0 to 100) motor and cognitive subscores by the Rasch method. FIM scores
      were compared using multiple linear regression to control for differences in
      rehabilitation diagnosis and other confounding factors between the ESRD and other
      patients. ESRD subgroups were compared using one-way analysis of variance. The
      mean discharge motor FIM score unadjusted for confounders was lower in ESRD than
      general rehabilitation patients (45.18 vs 50.63), and the difference after
      regression analysis (7.63 points lower in the ESRD group) was significant (p <
      .01). The mean motor FIM score gain after regression analysis for the two groups
      showed only a near significant (p = .06) difference, with the gain among ESRD
      patients being 3.15 points lower. Discharge settings were similar, with 89% of
      ESRD patients and 87% of patients without ESRD being discharged home. ESRD
      patients on hemodialysis had similar FIM scores to patients with renal
      transplantation. ESRD patients with stroke had significantly lower (p < .05)
      discharge motor and cognitive scores than ESRD patients with generalized weakness
      or amputation. In addition, stroke patients with ESRD showed significantly lower
      motor FIM score gains than stroke patients without ESRD (5.09 vs 11.08; p =
      .002).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717837
TI  - Functional reach in wheelchair users: the effects of trunk and lower extremity
      stabilization.
AB  - Our purpose was to compare the effects of using wheelchair trunk and lower
      extremity stabilization on sitting trunk mobility and functional reach of
      wheelchair users. Seven subjects with paraplegia who averaged 35.6 years of age
      and nine able-bodied control subjects with an average age of 26.0 years
      participated in this study. Each subject's functional reach in the transverse and
      sagittal planes was video-recorded in each of three conditions, randomized in
      order: (1) without a belt; (2) with a neoprene chest belt; and (3) with a webbing
      thigh belt. The area circumscribed by each subject's functional reach under each
      condition was processed using the Motion Analysis Expert Vision Flextrak program.
      Functional reach in each belting condition was compared within each subject and
      between able-bodied controls and subjects with high and low thoracic levels of
      paraplegia. This study showed that in the sagittal plane, subjects with both high
      and low thoracic levels of paraplegia were able to substantially increase the
      area of their functional reach when using a chest belt when compared with the
      thigh belt or no-belt condition. The mean area of their sagittal plane functional
      reach increased by over 50% by stabilizing the chest to the wheelchair using a
      neoprene belt. However, in the transverse plane, only those individuals with
      lower thoracic paraplegia (T8 to L1) gained substantial benefit from chest
      strapping, increasing the area of their functional reach by a mean of 24%. In
      contrast, able-bodied control subjects gained no benefit in functional reach from
      either belting condition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717838
TI  - Improvement in wheelchair propulsion in pediatric wheelchair users through
      resistance training: a pilot study.
AB  - Six children, three with cerebral palsy and three with myelomeningocele,
      participated in a progressive, 8-week, circuit muscular strength training
      program. The program was designed to improve wheelchair propulsion, an important
      functional outcome. Subjects performed three sets of six-repetition maximum (6
      RM) upper body strength exercises, three times a week. Exercises included
      shoulder flexion, extension, abduction, internal and external rotation, elbow
      flexion, extension, and shoulder flexion/elbow extension (bench press). Subjects
      exercised quickly with little rest between each set for approximately 30 minutes
      per session. All children used wheelchairs extensively and participated in a 50
      m, and a 12-minute wheelchair propulsion test before and after the 8-week
      program. The sign test was used to determine if statistically significant (P < or
      = .05) wheelchair propulsion or 6-RM changes occurred over the training period.
      Subjects improved significantly (P < or = .031) in all muscular strength (6-RM)
      measures and the 12-minute distance test. There was a trend toward improvement in
      the 50-meter test, although this change was not significant (P < or = .05). The
      results indicate that progressive resistance exercise training seems to improve
      muscular strength and wheelchair performance in selected disabled children.

PMID- 7717839
TI  - Physical determinants of independence in mature women.
AB  - The purpose of this study was to determine the relationship in mature women
      between muscle strength and whole body oxidative capacity and the ability to
      perform activities of daily living (ADL). Sixty-one women (mean age 69 years)
      without major disease or disability were recruited from either a community
      exercise center or a personal care facility. Physiological measurements consisted
      of peak oxygen consumption on a cycle ergometer (VO2peak) and one repetition
      maximum strength of nine muscle groups (1-RM). Ability to perform ADL was
      measured with a balance and gait test, "Bag Carrying Test", and ADL
      questionnaires. Significant correlations were found with VO2peak and calf muscle
      strength and ability to perform ADL, with weaker or no correlations for other
      muscle groups. For some relationships, it was possible to identify the minimum
      level of physiological functioning associated with successful performance of
      independence tasks. In summary, physiological capacities, particularly VO2peak
      and strength of the calf muscles, predicted ability to perform activities needed
      for functional independence in healthy mature women.

PMID- 7717840
TI  - High-voltage pulsed current: its influence on diameters of histamine-dilated
      arterioles in hamster cheek pouches.
AB  - Results from five independent studies from our laboratory indicate that cathodal
      high-voltage pulsed current (HVPC) significantly curbs posttraumatic edema
      formation in several animal models. Conversely, anodal HVPC did not curb edema
      formation. The mechanism by which HVPC reduces edema formation is unknown. We
      hypothesize that HVPC causes a decrease in local blood flow by active
      vasoconstriction of arterioles. Because we had previously observed positive
      effects with cathodal HVPC but not anodal HVPC, we further hypothesized that
      cathodal but not anodal HVPC would reduce diameters of histamine-dilated
      arterioles. Changes in diameters of resistance arterioles (5 to 30 microns
      internal diameter) were measured directly in cheek pouches of anesthetized
      hamsters, using in vivo video microscopy. Three minutes after superfusion with
      the inflammatory mediator (histamine) was begun, sensory-level HVPC at 120pps was
      applied concurrently for 30 minutes. Five animals received cathodal HVPC and five
      received anodal HVPC. Four other animals received 30-minute treatments of both
      cathodal and anodal HVPC in random order. Three control animals received
      histamine without HVPC for 30 minutes. Diameter changes of one arteriole from
      each cheek pouch was measured every 20 seconds throughout the treatment period.
      One-way analysis of variance (ANOVA) with repeated measures showed that diameters
      of histamine-dilated controls varied little over 30 minutes, and that adding
      cathodal HVPC did not significantly alter diameters of arterioles superfused with
      histamine. However, applying anodal HVPC to histamine-dilated arterioles
      significantly reduced arteriolar diameters. These results do not support the
      hypothesis that cathodal HVPC curbs edema formation by increasing arteriolar tone
      in the injured area.

PMID- 7717841
TI  - Pulmonary embolism presenting as syncope in paraplegia: a case report.
AB  - Syncope as an initial presentation of pulmonary embolism is unusual. A 16-year
      old girl, with T7 paraplegia after a traumatic spinal cord injury, developed
      syncope on the 33rd hospital day. The episode occurred approximately 3 hours
      after her first tilting table training and just after her attendant had assisted
      passive range-of-motion exercise. Subsequent studies showed pulmonary embolism at
      the left lower branch of the left pulmonary artery, and the branch to lower
      segment of the lingual lobe. Doctors should be alert to possible diagnosis of
      pulmonary embolism in such high-risk patients, especially when new onset symptoms
      or signs appear.

PMID- 7717842
TI  - "Great mimicry" in a patient with tetraparesis: a case report.
AB  - The patient is a 63-year-old Chinese man who presented with tetraparesis and
      urinary incontinence. The initial diagnosis was cord compression from cervical
      spondylosis. The patient relapsed 3 months after cervical laminectomy. The
      transverse myelitis picture, left optic atrophy and suggestive brainstem evoked
      potentials led to treatment of a presumptive demyelinating process. The presence
      of vitiligo, however, led to detection of high titers of antinuclear antibodies
      (ANA) and presence of anti-nonhistone antibodies. The patient was then diagnosed
      to have a lupus (SLE)-like disease, which has not fully evolved. He was
      prescribed pulsed cyclophosphamide and prednisolone with significant gains both
      neurologically and functionally up to 1 year of follow-up. This report highlights
      the befuddling impact the disease process have on the clinicians in terms of
      diagnosis, treatment, and prognosis. That it can occur in men in the seventh
      decade of life heightens the need for awareness in our approach to the
      myelopathic patient.

PMID- 7717844
TI  - Effect of dietary fish oil on serum lipids and lipoproteins of rats fed diets
      differing in cholesterol and fat.
AB  - The investigation was attempted to clarify the effects of fish oil on the
      concentration of lipids in serum and lipoproteins in rats fed diets differing in
      cholesterol and fat. Male Sprague-Dawley rats were maintained on low-fat/high-fat
      diets without and with 1.5% cholesterol (base diets) for 28 days. Half of each
      group was then switched to a fish oil diet for 20 days with 5.6% fish oil for
      exchange of coconut oil and beef tallow. Total cholesterol in rat serum was
      increased following feeding high amounts of dietary cholesterol. This increase
      was due to raised VLDL and LDL cholesterol. Rats fed the high-cholesterol/high
      fat diet had lower HDL cholesterol concentration than groups fed the other base
      diets. Dietary fish oil lowered serum and lipoprotein cholesterol, even in the
      presence of dietary cholesterol. In rats fed the high-fat/cholesterol-free diet
      triglyceride levels in total serum and VLDL were higher than in rats fed the
      other base diets. The hypertriglyceridemia in rats was diminished fed dietary
      cholesterol. Serum triglyceride concentration was markedly lowered by fish oil,
      whereas, this effect reached significance only using cholesterol-free diets. This
      was mainly associated with a reduction in VLDL triglycerides. Fish oil lowered
      HDL triglycerides only in rats fed the low-fat diet without cholesterol. Lipid
      components in the base diets did not influence serum and LDL phospholipids. Rats
      fed the high-fat/cholesterol-free diet had a higher VLDL phospholipid level than
      the other base groups. Irrespective of the base diet, phospholipid levels in
      serum and lipoproteins were markedly reduced by dietary fish oil. In conclusion,
      this study suggests that other dietary lipids should be considered when examining
      the hypolipemic effect of fish oil.

PMID- 7717843
TI  - Manipulation of microbial activity in the rumen.
AB  - Different methods of optimizing feed conversion into nutrients in the rumen are
      now available to scientists. But the rumen must be considered as an integrated
      system and this makes it difficult to rationalize manipulation. The observed
      result of any treatment is a combination of several interactive reactions. Any
      change to one component of the system has several uncontrolled effects on other
      components. The positive effects aimed for are sometimes associated with
      undesirable effects. Numerous chemical additives have been studied during the
      last two decades among which ionophore antibiotics represent the most important
      group. The interest of non-ionophore antibiotics, methane inhibitors, and
      compounds inhibiting proteases or deaminases, has also been considered during the
      last years. The observed effects of these chemical additives on animals, and
      their possible mode of action on rumen microbes and on animal metabolism, are
      discussed. However, the risks of the presence of residues in meat and milk are
      questioned by consumers. Microbial activity in the rumen can be altered by
      feeding animals with large amounts of certain food constituents (fats, starch) or
      minerals (buffer substances). The responses in the rumen to these dietary
      conditions are analyzed in terms of the digestive effects on plant cell wall
      degradation and microbial protein synthesis. Modification of the rumen microbial
      population is now considered as a possible approach to rumen manipulation by
      scientists. The effects on digestion of the elimination of ciliate protozoa
      (defaunation) are presented. The feasibility of these objectives, from a
      practical standpoint, is discussed. Finally, there is an overview of the effects
      of the addition of live yeasts (Saccharomyces cerevisciae), or fungi (Aspergillus
      orizae), used as probiotics. A possible mode of action of probiotics on the rumen
      ecosystem is suggested.

PMID- 7717845
TI  - Changes of the activities of urea cycle enzymes extracted from rat liver after
      surgical reduction of stomach capacity and after feeding a high-fat diet.
AB  - Fourty-two Wistar FL tribe rats were divided into control groups, fed a high-fat
      diet or subjected to surgical reduction of stomach capacity by 75%. After 60 days
      of experiment we observed decrease of animal body weight gain, as well as
      decrease of ornithine transcarbamylase and arginase activity. As indicated by the
      activity of these enzymes high-fat diet leads to an increase in urea cycle
      activity probably due to metabolic and hormonal imbalance. The utilisation of
      carbamoylphosphate for the pyrimidine biosynthesis pathway did not seem to change
      the ATC-ase activity.

PMID- 7717846
TI  - [Energy and nitrogen metabolism of pregnant and lactating sows and suckling
      piglets. 5. Energy and nitrogen metabolism of pregnant sows].
AB  - The energy and nitrogen metabolism of pregnant sows was measured with the method
      of indirect calorimetry in dependence on the number of gestation (1,2 and 4), on
      the energy supply (120, 100 and 80% of the requirement recommendation) and on the
      gestation stage. Values of maintenance requirement and of energy and nitrogen
      utilization for body deposition were calculated on the basis of results of energy
      and nitrogen metabolism. The energy maintenance requirement increased from 389 to
      435 and 473 kJ metabolizable energy per kg LW0.75.d with rising number of
      gestation. The heat production increased from 85th to 115th day of gestation by
      6%. The efficiency of the partial energy utilization for the energy deposition
      amounted to 66% on the average. The efficiency of the partial utilization of
      digestible nitrogen for the nitrogen deposition was calculated to 75%. The
      nitrogen maintenance requirement values amounted to 0.5 and 0.4 g digestible
      nitrogen per kg LW0.75.d in the 1st and 2nd half of gestation.

PMID- 7717847
TI  - [Effect of physical treatment of rapeseed expeller, wheat, corn and corn gluten
      feed on the degradability in the rumen and the enzymatic in vitro digestibility
      of nondegraded crude proteins].
AB  - The influence of physical treatment-expansion and flaking-on crude proteins
      degradability in the rumen was studied in maize, maize-gluten feed, rape
      extracted meal and in the expanded one at 120 degrees C and 150 degrees C, rape
      cake, wheat and flaked wheat by in sacco method. The enzymatic digestibility of
      crude protein in the rumen undegraded residues of the above mentioned feeds was
      determined by an enzymatically in vitro method. The treatment of feed decreased
      significantly the original solubility and theoretical degradability of crude
      proteins, and the amount of undegraded crude proteins was increased. Positive
      influence on the amount of enzymatically digested crude protein was determined in
      rape expanded at 120 degrees C and 150 degrees C (60, 61 and/or 68%). Flaking of
      wheat had a similar effect. Enzymatic digestibility at undegraded rests where
      increased by 8-10% after the heat treatment and it remained almost unchanged in
      expanded maize-gluten feed.

PMID- 7717848
TI  - Molecular dosimetry of DNA adducts in rainbow trout (Oncorhynchus mykiss) exposed
      to benzo(a)pyrene by different routes.
AB  - Farm raised rainbow trout (Oncorhynchus mykiss) were exposed by various routes to
      benzo(a)pyrene (BP) as a representative carcinogenic polycyclic aromatic
      hydrocarbon (PAH). Following exposure of fish to the chemical by intraperitoneal
      (i.p.) injection, 32P-postlabelling studies indicated that non-feral trout were
      relatively resistant to the formation of BP-DNA adducts in liver. No adducts were
      detected in fish exposed to single doses (20 mg/kg) of BP. Multiple exposures
      (e.g. 2 x 25 mg/kg) were necessary in order for adducts to be detected,
      indicating that induction of the metabolising enzymes required for the
      bioactivation of BP is necessary. These studies provided reference information on
      DNA adducts for comparison with data from subsequent experiments at
      environmentally realistic low level exposures. Two types of low level aquatic
      exposure were carried out. The first procedure exposed fish for 30 days to a
      nominally constant low level (1.2 and 0.4 micrograms/l) of a homogeneous
      dispersion of BP in water, to simulate low level aquatic environmental exposures.
      Following 32P-postlabelling analysis of the liver DNA of exposed fish, BP-DNA
      adducts were not detected. In the second procedure, fish were exposed to a
      constant low level of BP (ca. 0.5 micrograms/l) for 15 days then to a pulse (60
      micrograms/l) which was allowed to naturally decline (to ca. 2 micrograms/l)
      during a further 15 days. Following this exposure, significant levels of BP-DNA
      adducts were detected in livers of trout. The effect of dietary exposures was
      investigated by feeding trout a diet containing either 58 micrograms or 288
      micrograms BP per day for 6 days, equivalent to total doses of 43 mg/kg and 216
      mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717849
TI  - Metabolism of a glucuronide conjugate of 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone in rats.
AB  - Besides 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), [4
      (methylnitrosamino)-1-(3-pyridyl)butl-yl]-beta-O-d-glucosidu ronic acid (NNAL
      Glu) is another important metabolite of the tobacco-specific nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) which has been detected in the
      urine of tobacco users and non-smokers heavily exposed to sidestream cigarette
      smoke. In order to evaluate the toxicological significance of NNAL-Glu formation
      and excretion, the metabolism of [5-3H]-NNAL-Glu was studied in rats. Five male
      F344 rats were administered 3.7 mg/kg [5-3H]-NNAL-Glu by i.v. injection and the
      metabolites in urine analysed by HPLC. More than 90% of the radioactivity was
      excreted in urine within the first 24 h. Unchanged NNAL-Glu accounted for 81.2 +/
      3.1% of the total radioactivity; the remaining part of the dose appears to be
      deconjugated resulting in the urinary excretion of NNAL (3.6 +/- 1.7%) and its
      alpha-hydroxylation (11.5 +/- 2.2%) and N-oxidation (3.6 +/- 1.6%) products. The
      presence of alpha-hydroxylation products of NNAL-Glu in urine suggests that this
      NNK metabolite may be activated in vivo to carcinogenic intermediates.

PMID- 7717850
TI  - Dose and route dependency of metabolism and toxicity of chloroform in ethanol
      treated rats.
AB  - The effects of a single dose of ethanol on the metabolism and toxicity of
      chloroform administered to rats per os (p.o.), intraperitoneally (i.p.), or by
      inhalation (inh) at different doses were investigated. Rats that had been given
      either ethanol (2 g/kg) or vehicle (water) alone at 4 p.m. on the previous day
      were challenged with chloroform at 10 a.m. p.o. (0.01, 0.2, or 0.4 g/kg), i.p.
      (0, 0.1, 0.2, or 0.4 g/kg), or inh (for 6 h each at 0, 50, 100, or 500 ppm). The
      ethanol treatment, which had no influence on the intake of food and water,
      increased chloroform metabolism in vitro about 1.5-fold with no significant
      influence on liver glutathione content. The treatment had a dose-dependent effect
      on the metabolism and toxicity of chloroform, and the effect differed depending
      on the route of administration. Compared at the same dose level, the area under
      the curve (AUC) of blood chloroform concentration was invariably smaller
      following p.o. than i.p. administration. In accordance with this, chloroform
      administered p.o. caused more deleterious hepatic damage than the same amount of
      chloroform administered i.p. Although ethanol treatment had no significant
      influence on the AUC at any dose by any route of administration, the toxicity of
      p.o.-administered chloroform was significantly higher in ethanol-treated rats
      than in control rats at a dose as low as 0.1 g/kg, whereas no significant
      difference was observed in toxicity between both groups of rats at such a low
      dose administered i.p.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717851
TI  - Allyl alcohol cytotoxicity in isolated rat hepatocytes: mechanism of cell death
      does not involve an early rise in cytosolic free calcium.
AB  - We examined the effect of a toxic concentration of allyl alcohol (0.5 mM) on
      intracellular calcium concentrations in isolated rat hepatocytes. An increase in
      phosphorylase a activity was evident in the hepatocytes after 30 min of
      incubation with allyl alcohol, suggesting that the toxicant may produce an early
      rise in cytosolic free calcium. The increase in phosphorylase a activity was not
      reversed by the addition of dithiothreitol (DTT), a sulfhydryl compound that
      reverses the events that initiate cell killing by allyl alcohol. When
      intracellular calcium concentrations were measured directly, using fura-2 as the
      calcium indicator, there was no effect of allyl alcohol on cytosolic free calcium
      during the first 60 min of exposure, a critical period for development of
      irreversible damage. Incubation with allyl alcohol did not interfere with the
      measurement of intracellular calcium. The increases in cytosolic free calcium
      produced by phenylephrine or ATP were similar to those reported by others and not
      affected by the presence of allyl alcohol. The results from this study
      demonstrate that increased cytosolic free calcium is not essential for allyl
      alcohol-induced cytotoxicity to isolated rat hepatocytes.

PMID- 7717852
TI  - Comparison of hepatotoxicity caused by mono-, di- and tributyltin compounds in
      mice.
AB  - The in vivo induction of hepatotoxicity, as evaluated by the activity of
      ornithine carbamyl transferase in serum, was investigated in mice administered
      orally with the following three butyltin compounds: tributyltin chloride (TBTC),
      dibutyltin dichloride (DBTC) and monobutyltin trichloride (MBTC). The minimal
      concentrations of TBTC and DBTC that caused hepatotoxicity at 24 h after oral
      administration were 180 mumol and 60 mumol/kg, respectively, while MBTC did not
      induce liver injury even at 7000 mumol/kg. Additionally, when the administered
      doses were equivalent (180 mumol/kg), a time course (3-96 h) study revealed that
      the hepatotoxicity of TBTC and DBTC appeared at 24 and 12 h, respectively, but
      that MBTC showed no hepatotoxicity even at 96 h. The amounts of Sn excreted into
      urine for 4 days were 1.5 fold greater with TBTC than with DBTC treatment and
      were lowest in MBTC group. Similarly, the total liver Sn content was 2- to 5-fold
      greater in the TBTC group than in the DBTC group whereas the liver Sn content in
      the MBTC treatment showed the lowest value throughout the 3- to 96-h period.
      Thus, the non-hepatotoxicity of MBTC may be due either to low absorption through
      the digestive tract of mice or to the low levels of Sn in liver; however, the
      level of Sn in liver was not associated with the induction of hepatotoxicity by
      TBTC and DBTC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717853
TI  - Comparative toxicity of methyl isocyanate and its hydrolytic derivatives in rats.
      I. Pulmonary histopathology in the acute phase.
AB  - The present study describes the acute histopathological changes induced by methyl
      isocyanate (MIC) in the lungs of rats at 24 h after a single exposure to varied
      concentrations/doses of MIC by inhalation and subcutaneous (s.c.) routes and also
      delineates the effects due to the hydrolytic derivatives of MIC, viz.,
      methylamine (MA) and N,N'-dimethyl urea (DMU). MIC, either inhaled or
      administered s.c., resulted in a wide range and extent of histopathological
      changes in the lungs, proportional to the exposure concentration/dose. The
      salient, effects of inhaled MIC are acute necrotizing bronchitis of the entire
      respiratory tract accompanied by varying degrees of confluent congestion,
      hyperemia and interstitial and intra-alveolar edema, while MIC administered s.c.
      led to prominent vascular endothelial damage, congestion and severe interstitial
      pneumonitis with apparently normal bronchial epithelium; and intra-alveolar edema
      only with the high dose. The only noteworthy lesion produced by MA and DMU (to
      some extent) was interstitial pneumonitis, suggesting their possible involvement
      in the subsequent inflammatory response of MIC. Except, for the endothelial
      changes, the overall spectrum of the histopathological lesions is quite
      comparable to those observed in the lungs of Bhopal victims during the acute
      phase.

PMID- 7717854
TI  - Comparative toxicity of methyl isocyanate and its hydrolytic derivatives in rats.
      II. Pulmonary histopathology in the subacute and chronic phases.
AB  - This paper describes the long-term (subacute and chronic) histopathological
      effects in the lungs of rats subjected to a single exposure to methyl isocyanate
      (MIC) by both the inhalation and subcutaneous (s.c.) routes as well as the role
      of methylamine (MA) and N,N'-dimethyl-urea (DMU), the hydrolytic derivatives of
      MIC in eliciting the observed changes. At the subacute phase, the intraalveolar
      and interstitial edema were prominent only in the inhalation group as against the
      more pronounced inflammatory response in the s.c. route. With the progress of
      time the evolution of lesions appeared to be similar, culminating in the
      development of significant interstitial pneumonitis and fibrosis. MA, one of the
      hydrolytic derivatives of MIC, also caused interstitial pneumonitis progressing
      to fibrosis, albeit to a lesser extent than MIC, indicating its contribution to
      the long-term pulmonary damage. The diffuse interstitial pulmonary fibrosis
      observed at 10 weeks after a single exposure to MIC by either route is of greater
      significance in the context of the occurrence of pulmonary fibrosis in the late
      autopsies of Bhopal gas victims and also clinical sequelae in some of the
      survivors.

PMID- 7717855
TI  - Assessment of the labelling index of cohorts of the pancreatic islet cell
      population in phenobarbitone-treated male rats using a double immunohistochemical
      technique for 5-bromo-2'-deoxyuridine and pancreatic hormones.
AB  - A previous study demonstrated that administration of phenobarbitone to male AP
      Wistar rats for up to 7 days caused alterations in labelling indices (LIs) in
      several different tissues (including a reduction of the endocrine pancreas
      population LI) as determined by immunohistochemical visualisation of 5-bromo-2'
      deoxyuridine (BrdU) incorporation into S-phase nuclei. The primary objective of
      this study was to determine whether treatment with phenorbarbitone influenced the
      replicative states of specific cohorts of the islet (of Langerhans) cell
      population or generated a uniform depression of LI. Quantitation of the LIs of
      individual islet cell cohorts was achieved by utilisation of a dual
      immunohistochemical staining method for BrdU and islet hormones (insulin,
      glucagon and somatostatin) using a sequential peroxidase anti-peroxidase
      (PAP)/alkaline phosphatase anti-alkaline phosphatase (APAAP) method employing
      diaminobenzidine and New Fuchsin chromogens, respectively. We observed
      reductions, increases and no change in LIs of insulin-, glucagon- and
      somatostatin-positive cells, respectively. We conclude that the decreased LI of
      the insulin-positive cohort was not countered entirely by the LI increase in the
      glucagon-positive cohort due to the larger size of the former. Furthermore, the
      effects of phenobarbitone treatment are not manifested generally in the islet
      cell population but in the insulin- and glucagon-positive cohorts only. The
      causation of these effects is unknown but is likely to be due to enhanced
      carbohydrate and hormone metabolism. We believe that the visualisation and
      quantitation of replicating cells in specific hormone-positive cohorts of the
      islet cell population provide opportunities for understanding the influence of
      xenobiotics and disease processes on pancreatic function.

PMID- 7717856
TI  - Time course of effects of tetraethoxysilane (TEOS) on the kidney and blood
      silicon concentration in mice.
AB  - To clarify the time course of toxicological effects of tetraethoxysaline
      [Si(OC2H5)4, TEOS] on the kidney and the relationship between blood silicon
      levels (Si-B) and the effects, 250 mg/kg or 500 mg/kg TEOS was intraperitoneally
      administered to ten 5-week-old male ICR mice (SPF grade) in each group, and
      morphological and functional changes of the kidney were assessed at 12 h, 24 h, 3
      days and 2 weeks after administration of TEOS. Injury to tubular epithelial cells
      was observed in mice killed 12 and 24 h after administration, and its severity
      increased with increasing dosage. The mean values of blood urea nitrogen
      exhibited dose-related increase in mice sacrificed 24 h after the administration.
      The concentrations of Si-B increased in order of the administered doses of TEOS,
      and then decreased steadily. The results of Si-B were consistent with the concept
      that renal toxicity of TEOS is mediated by siliceous compounds. The kidney was
      recovering from injury 3 days after administration, and had developed
      tubulointerstitial nephritis, which could be regarded as repaired lesion of acute
      injury, by 2 weeks after administration.

PMID- 7717858
TI  - Formation and removal of DNA adducts in Fischer-344 rats exposed to 2,4
      diaminotoluene.
AB  - 32P-Postlabeling was used to examine DNA adduct formation and removal in Fischer
      344 rats exposed to the animal carcinogen 2,4-diaminotoluene (DAT). Adduct
      formation and persistence were compared between target (liver and mammary gland)
      and non-target organs (kidney and lung) to determine if possible differences
      could explain the observed organ specificity of DAT induced carcinogenesis. The
      effects of different exposure conditions on DNA adduct formation and removal were
      also examined by varying the concentration and frequency of compound
      administration. DAT produced three distinct DNA adducts. Among the organs
      examined, DNA binding was highest in the liver, with levels approximately 10
      times greater than that of the mammary gland and up to 50 times greater than of
      the two nontarget sites. Despite the large differences in the initial extent of
      adduct formation, the persistence of adducts among sites was not significantly
      different. In the liver, there were dose-dependent differences in DNA adduct
      formation, but adduct removal following different dosages did not vary
      significantly. The effects of multiple administration on DNA adduct formation and
      removal were examined by treating rats with 5 mg/kg DAT daily for 10 consecutive
      days. Adduct yields from multiple treatment were greater than from a single 50
      mg/kg exposure. The persistence of adducts following multiple treatment was also
      greater than after an equivalent single exposure. The results demonstrated organ
      specific and dose-dependent differences in initial extent of DNA adduct
      formation, but no differences in adduct persistence. However, the results did
      suggest that adduct formation and persistence may change with repeated
      administration of DAT.

PMID- 7717859
TI  - Studies on the muscle toxicant 2,3,5,6-tetramethyl p-phenylenediamine: effects on
      various biomarkers including urinary creatine and taurine.
AB  - The effect of the specific muscle toxicant, 2,3,5,6-tetramethyl p
      phenylenediamine (TMPD), on urinary creatine and taurine, markers of testicular
      and liver dysfunction, respectively, has been investigated in male Sprague-Dawley
      rats. Damage to the gastrocnemius and soleus muscles was accompanied by a rise in
      serum creatine kinase (predominantly the muscle-specific isoenzyme, CK-MM),
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Increases in
      serum alpha-hydroxybutyrate dehydrogenase (HBDH) and total lactate dehydrogenase
      (LDH) (mainly isoenzymes, LDH1 and LDH2), occurred but only minor damage to the
      heart and no rise in CK-MB, (heart muscle isoenzyme) was seen. Damage to stage
      XIV tubules in the testis was evident histologically after the highest dose. This
      was accompanied by an increase in LDH-C4 testis-specific isoenzyme and a decrease
      in serum testosterone. Apart from reduced serum albumin, no other serum
      parameters indicated liver damage and there was only slight liver steatosis in
      some animals at the highest dose. Urinary taurine was not significantly raised
      after any dose of TMPD, but there was a significant increase in urinary creatine
      after the highest dose. It can be concluded that in the presence of discrete
      muscle damage, the use of urinary taurine and urinary creatine as markers of
      liver and testicular dysfunction, respectively, is not confounded. However, a
      variety of different markers should be used in conjunction to fully delineate the
      tissue damage due to toxic chemicals.

PMID- 7717857
TI  - Embryotoxic effects of L-691,121, a class III antiarrhythmic agent, in rats.
AB  - L-691,121 is a class III antiarrhythmic agent which blocks potassium currents,
      leading to prolongation of cardiac potential and prevention of cardiac
      arrhythmia. In a developmental toxicity study in rats, there was a dose-dependent
      decrease in embryonic/fetal survival, and death of the entire litter was seen at
      an oral dose of 0.8 mg/kg per day. The critical period for embryolethality was
      determined as gestational days (GD) 10-13. In a study where females received 1
      mg/kg on a critical day (GD 10 or 12) and were killed at 24-h intervals, a high
      embryonic mortality was seen at 72 h (GD 10 treatment) or 48 h (GD 12 treatment)
      after dosing. The surviving embryos had morphological abnormalities such as
      enlarged cardiac tube and pericardium, generalized edema, and hematoma. In order
      to investigate a possible mechanism for the embryolethality, GD 11 embryos were
      dissected from females at 4 h after dosing of 1 mg/kg and incubated for 5 h in
      vitro. The embryonic heart rates were decreased for the first 2 h after
      incubation but tended to recover to control levels thereafter. When GD 11 embryos
      were incubated for 4 h with the drug, there were decreases in the heart rates
      during the entire observation period. In a washout study where the embryos were
      transferred to drug-free medium after 1-h exposure, decreased heart rates
      recovered to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717860
TI  - Non-reactivating effects of HI-6 on hippocampal neurotransmission.
AB  - Effects of the oxime HI-6, unrelated to reactivation of acetylcholinesterase
      (AChE), on field potentials in the dentate gyrus of the rat hippocampus following
      AChE inhibition, were investigated both in vitro and in vivo. In hippocampal
      slices, AChE inhibition decreased the perforant path evoked population spike
      amplitude (PSA). This effect could be prevented by pre-incubation of the slices
      with atropine (0.1-1 microM) or with the M1 muscarinic receptor antagonist
      pirenzepine (1 microM). A similar preventive effect was found after pre
      incubation with the GABAA antagonist picrotoxin (20 microM), suggesting that the
      effects of AChE inhibition in vitro may be due to an enhancement of GABAergic
      inhibitory activity via activation of M1-muscarinic receptors. The effects of
      AChE inhibition in vivo were variable; both increases and decreases of the PSA
      were found. Following AChE inhibition, HI-6 increased the PSA dose-dependently,
      both in the in vivo and in the in vitro hippocampus. At higher oxime doses the
      perforant path stimulation elicited multiple population spikes. The effects of
      the oxime were presumably not mediated by an antagonism of cholinergic receptors,
      since they could not be mimicked with cholinergic antagonists like atropine,
      mecamylamine or gallamine. Further testing of the nature of the HI-6 effect in
      hippocampal slices in vitro, using a paired antidromic-orthodromic stimulation
      protocol, showed that HI-6 may interfere with GABAergic inhibition.

PMID- 7717861
TI  - A laser Raman spectroscopic study on the interaction of alkylmercury with thiol
      and sulfur-containing compounds.
AB  - The interaction of the methylmercury cation with sulfur compounds in aqueous
      solution at physiological pH was studied by laser Raman spectroscopy. Metal
      binding is shown to occur preferentially at the sulfhydryl group of sulfur
      compounds. Raman frequencies of S-Hg stretching of the one-to-one methylmercury
      sulfhydryl or sulfur-containing complexes were observed at approximately 330 cm
      1. There was no frequency shift when ligands were exchanged. However, the
      relative intensity (I S-Hg/I C-Hg) was different. The relative intensities of
      MeHg-thioglycerol, MeHg-cysteine and MeHg-2-mercaptobenzothiazole were 0.18, 0.43
      and 0.62, respectively. Methyl-mercury shifted from combination states of lager
      relative intensity to ones of smaller relative intensity. These results may cast
      light on the distribution and excretion mechanisms of methylmercury in the human
      body.

PMID- 7717862
TI  - Suppression of interleukin-1 beta and tumour necrosis factor-alpha biosynthesis
      by cadmium in in vitro activated human peripheral blood mononuclear cells.
AB  - Cadmium is a highly toxic element responsible for acute and chronic toxicity in
      man. There is evidence that cadmium induces pathophysiological effects by
      modulating components of the immune system. Cytokines are being increasingly
      recognized as essential mediators of normal and pathologic immune responses.
      Cadmium at concentrations varying from 1.0 x 10(-4) to 3.3 x 10(-6) M inhibited
      the phytohemagglutinin induced production of interleukin-1 beta and tumour
      necrosis factor-alpha, in in vitro activated human peripheral blood mononuclear
      cells. The messenger RNA levels of interleukin-1 beta and tumour necrosis factor
      alpha were examined during a 24-h culture period, at different time points. The
      decreased messenger RNA levels at the time points of the maximum expression of
      interleukin-1 beta and tumour necrosis factor-alpha indicate that cadmium
      suppresses their production at the transcriptional level.

PMID- 7717863
TI  - A copper deficient diet prevents hepatic copper accumulation and dysfunction in
      Long-Evans Cinnamon (LEC) rats with an abnormal copper metabolism and hereditary
      hepatitis.
AB  - Long-Evans Cinnamon (LEC) rats that develop spontaneous hepatitis due to an
      inherently abnormal Cu metabolism have recently been established. This
      investigation concerns the effects of a Cu-deficient diet on the Cu metabolism
      linked to hepatic injury in LEC rats. The hepatic Cu concentration at 30 days
      after birth was 94 +/- 4 Cu micrograms/g liver in LEC rats, whereas that of
      Fischer rats at the same age was 7 +/- 1 Cu micrograms/g. From 30 days after
      birth, all rats were fed a semisynthetic diet with two different levels of Cu,
      0.5 or 30 micrograms/g food, for 35 days. In LEC rats fed a Cu-deficient diet
      (0.5 microgram/g), the hepatic Cu concentration was 39 +/- 7 micrograms/g. The Cu
      normal diet (30 micrograms/g) LEC group had a concentration of 357 +/- 15
      micrograms/g in the hepatic Cu. The group had significantly higher aspartate
      aminotransferase (ASAT), alanine aminotransferase (ALAT) and gamma-glutamyl
      transferase (GGT) levels than did the LEC rats given the Cu-deficient diet. These
      results suggest that the occurrence of acute hepatitis in LEC rats can be
      prevented by feeding the animals a Cu-deficient diet.

PMID- 7717864
TI  - Relationship between acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      and disturbance of intermediary metabolism in the Long-Evans rat.
AB  - The aim of this study was to examine the acute toxicity of 2,3,7,8
      tetrachlorodibenzo-p-dioxin, (TCDD) in a rat strain other than the Sprague-Dawley
      (S-D) rat, for which most of our data have been generated thus far. Doses for the
      biochemical study were selected based on an acute range-finding study, which
      indicated that Long-Evans (L-E) rats are somewhat less susceptible to TCDD
      toxicity than are S-D rats. Male L-E rats were dosed orally with 10, 20, 45, 67,
      100 and 150 micrograms/kg TCDD. Body weight and feed intake were dose-dependently
      decreased prior to killing of the animals. Eight days after dosing, animals were
      killed and tryptophan, total T4 (TT4) and total T3 (TT3) levels were determined
      in serum, whereas the activities of ethoxy-resorufin-O-deethylase (EROD),
      phosphoenolpyruvate carboxykinase (PEPCK), gamma-glutamyl transpeptidase (gamma
      GT) and tryptophan 2,3-dioxygenase (TdO) were measured in liver. EROD activity
      was fully induced at all doses studied, indicating that as in S-D rats, Ah
      receptor-mediated effects do not seem to play any major role in the acute
      toxicity of TCDD in this rat strain either. Hepatic PEPCK activity was dose
      dependently decreased in a similar dose range as in S-D rats, indicating
      inhibition of gluconeogenesis. Feed intake was dose-dependently decreased as a
      result of a dose-dependent elevation in serum tryptophan levels, which in turn
      were related to reduced liver TdO activity. Hepatic gamma-GT activity was also
      dose-dependently reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717865
TI  - Peri- and postnatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: effects on
      physiological development, reflexes, locomotor activity and learning behaviour in
      Wistar rats.
AB  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat
      offspring were studied after administration of a loading dose of 300 or 1000 ng
      TCDD/kg body wt on day 19 of pregnancy, followed by weekly maintenance doses of
      120 or 400 ng TCDD/kg body wt. The dose regimens led to a fluctuation of average
      TCDD concentrations in the liver of the offspring of 4.9-14.9 ng/g (TCDD1000/400
      group) or 1.4-6.3 ng/g (TCDD300/120 group) during the course of the experiment.
      In both TCDD-exposed groups the body weight of the offspring was significantly
      lower on postnatal day 7 (PND 7); in the high dose group from PND 7 to PND 31.
      Some landmarks of postnatal development were retarded in the exposed groups; in
      particular, the vaginal opening was delayed for several days in both TCDD-exposed
      groups. The TCDD-exposed animals revealed a reduced ability to remain on a
      rotating rod. During reflex testing, the rate of successfully responding animals
      was higher in the exposed groups. No statistically significant differences in the
      locomotor activity between controls and TCDD-exposed offspring were detectable
      under our experimental conditions. In a discrimination learning test no effects
      on the learning ability were found. However, TCDD-exposed offspring showed an
      increase in unanswered trials during critical phases of the task. They also
      exhibited increased locomotor activity in a novel environment; prior to an
      amphetamine challenge dose of 1 mg/kg body weight. Amphetamine-induced activity
      was decreased in a dose-dependent manner.

PMID- 7717866
TI  - The hr locus and the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in
      newborn mice.
AB  - In mice, the recessive mutation hairless (hr) controls the cutaneous response to
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but its influence on TCDD's systemic
      toxicity is unclear. To clarify this, we compared the effects of lactational TCDD
      exposure on standardized litters of newborn HRS/J mice homozygous for either hr
      or + that were fostered by haired dams exposed to 0, 6, 8 or 12 micrograms
      TCDD/kg body weight on postnatal day 0. At 12 micrograms/kg, TCDD was lethal to
      both haired and hairless pups. At the lower doses (6 and 8 micrograms/kg) the
      survival of hr/hr pups was significantly lower than +/+ pups. Affected pups
      succumbed following a 1 to 2-day period of cachexia and wasting. As has been
      reported for other mouse strains, TCDD exposure impacted on their neonatal
      development and lessened the time to eye opening for both haired and hairless
      pups. However, the hairless animals were affected at lower doses than were the
      haired. The results of this study document that the hr/hr genotype does influence
      the systemic toxicity of TCDD in mice.

PMID- 7717867
TI  - Immunohistochemical localisation of six glutathione S-transferases within the
      nasal cavity of the rat.
AB  - Many xenobiotics induce lesions within the nasal cavity of experimental animals
      which are site specific. This site selectivity may be due to regional deposition
      within the nasal cavity and/or the localisation of biotransformation enzymes. We
      have developed methodology which allows immunohistochemical localisation of
      xenobiotic biotransformation enzymes in transverse sections of the rat nasal
      cavity identical to those normally taken for pathological examination. We report
      the application of this methodology to six isoenzymes of the glutathione S
      transferases (GSTs). All six isoenzymes were predominantly located within
      olfactory epithelium covering the ethmoturbinates (levels III and IV) and
      extending forwards into the dorsal meatus (level II). Squamous and transitional
      epithelia showed little or no staining while respiratory epithelium was weakly
      stained. Within the respiratory epithelium only the ciliated columnar cells and,
      to a lesser extent, some of the seromucous glands contained GSTs. Within
      olfactory epithelium the sustentacular cells, basal cells and subepithelial
      glands all stained positive for GSTs. The different cell types of olfactory
      epithelium preferentially express different GST isoenzymes: 1-1 and 2-2 were
      predominantly located in the subepithelial glands; 3-3, 4-4 and 8-8 in
      sustentacular and basal cells; 7-7 in basal cells.

PMID- 7717868
TI  - Studies on the comparative toxicity of S-(1,2-dichlorovinyl)-L-cysteine, S-(1,2
      dichlorovinyl)-L-homocysteine and 1,1,2-trichloro-3,3,3-trifluoro-1-propene in
      the Fischer 344 rat.
AB  - The renal tubular toxicity of various halogenated xenobiotics has been attributed
      to their enzymatic bioactivation to reactive intermediates by S-conjugation. A
      combination of high resolution proton nuclear magnetic resonance (1H NMR)
      spectroscopy of urine, renal histopathology and more routinely used clinical
      chemistry methods has been used to explore the acute toxic and biochemical
      effects of S-(1,2-dichlorovinyl)-L-cysteine (DCVC), S-(1,2-dichlorovinyl)-L
      homocysteine (DCVHC) and 1,1,2-trichloro-3,3,3-trifluoro-1-propene (TCTFP) up to
      48 h following their administration to male Fischer 344 (F344) rats. In the
      absence of gross renal pathology, 1H NMR urinalysis revealed increased excretion
      of the tricarboxylic acid cycle intermediates citrate and succinate following
      DCVC administration. In contrast, both DCVHC and TCTFP produced functional
      defects in the S2 and S3 segments of the proximal tubule that were confirmed
      histologically. In these cases, 1H NMR urinalysis revealed increased excretion of
      glucose, L-lactate, acetate and 3-D-hydroxybutyrate (HB) as well as selective
      amino aciduria (alanine, valine, glutamate and glutamine). The significance of
      the proximal nephropathies induced by DCVHC and TCTFP is discussed in relation to
      biochemical observations on other xenobiotics that are toxic by similar
      mechanisms.

PMID- 7717869
TI  - A morphological analysis of the short-term effects of benzene on the development
      of the hematological cells in the bone marrow of mice and the effects of
      interleukin-1 alpha on the process.
AB  - Chronic exposure of humans to benzene (BZ), a widely used industrial chemical and
      a ubiquitous environmental pollutant, causes aplastic anemia and acute myeloid
      leukemia. The purpose of the studies reported here was to determine whether the
      observed depression of bone marrow (BM) cellularity in mice administered benzene
      was reflected in a suppression of development of all of the hematopoietic
      lineages and to confirm the ability of interleukin-1 alpha (IL-1 alpha) to
      prevent BZ-induced BM cell depression. We report that BZ, administered twice per
      day for 2 days to C57B1/6J mice at a dose of 600 mg/kg body weight, caused a
      significant depression of the total number of nucleated BM cells per femur when
      measured on day 3. The observed depression reflects a complex situation that
      represents the net effect of a decrease in the total number of cells of the
      lymphocytic and erythroid lineages, along with an increase in the number of
      intermediate and terminally differentiated cells of the granulocytic lineage. An
      experiment to monitor the effects of BZ over a 7-day period showed a progressive
      depressive effect on the lymphocytes and an initial depression of the erythroid
      cells at day 3 that remained constant until day 7. Conversely, the numbers of
      intermediate and terminally differentiated granulocytes progressively increased
      over the 7 days. The BM appeared to recover from the depressive effects of BZ
      immediately upon cessation of exposure, as the number of nucleated BM cells began
      to rise by day 5 and was equal to that of the control group by day 7. The results
      expand our earlier finding (Renz and Kalf 1991) that the overall depression of BM
      cellularity occurs because of an inability of the stromal fibroblast to produce
      colony-stimulating factors essential for stem and progenitor cell survival. This
      results from inhibition by the BZ metabolite, hydroquinone (HQ), of the
      processing of pre-IL-1 alpha to the mature cytokine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7717870
TI  - Characterization of the tobacco glycoprotein surface binding property of heart
      and skeletal muscle cells. I. Modulation of the heart cell membrane TGP
      interaction by anti-TGP IgG.
AB  - Monolayers of L6 rat skeletal myoblast cells formed surface binding isotherms
      with the purified tobacco leaf glycoprotein TGP1 and the enriched cigarette tar
      glycoprotein TGP2. Scatchard analysis showed that the binding in the range of the
      limited concentrations tested was to a single class molecule and the calculated
      affinity constant (Kd) for TGP1 and TGP2 showed similar values (9.78 x 10(-13) M
      and 3.09 x 10(-13) M, respectively). The bound TGPs were almost totally displaced
      by excess nonradiolabeled molecules. The calculated Bmax of the L6 myoblast
      monolayer was 2.93 fmol for TGP1 and 0.217 fmol for TGP2 per 32.2 mm2. Guinea pig
      heart sarcolemma binding isotherms were also formed with radiolabeled TGP1 and
      TGP2. The interaction of tobacco leaf TGP1 with the heart cell membranes was
      irreversible because only 15-20% of the bound TGP1 was displaced by 100-fold, non
      labeled molecules but the interaction of tar TGP2 with heart sarcolemma was
      reversible and probably saturable. The heart sarcolemma TGP2 affinity constant
      (Kd) was 5.88 x 10(-7) M and the Bmax, 2.45 x 10(-8) M per 12.5 micrograms
      sarcolemma. Pretreatment of heart sarcolemma with increasing concentrations of
      leaf TGP1 did not displace tar TGP2 binding but its absorption on the membrane
      resulted in increased TGP2 sarcolemma attachment by a complex and unexplained
      mechanism. Increasing concentrations of the sera of 10 of 15 guinea pigs (67%)
      that received mainstream emissions of tobacco smoke from a University of Kentucky
      cigarette smoking machine for 152 days, displaced cigarette tar TGP2 heart cell
      sarcolemma attachment and this inhibition was significantly different from that
      produced by the sera of sham smoked and of non-exposed animals (Mann-Whitney
      test, p = 0.0082). Staphylococcus protein A inhibited the displacement of TGP2
      produced by the sera of cigarette smoke exposed guinea pigs and this observation
      indicated that this action was mediated by IgG molecules. The specific
      immunoprecipitation of a radiolabeled surface epitope of the L6 myoblast
      monolayers pretreated with TGP1 or TGP2 by immune IgG against TGP2 and by the IgG
      of an antiserum against standard TGP showed that the tobacco glycoproteins
      attached to a unit polypeptide of the plasma membrane of the muscle cells of
      approximately 76 kDa. These data support the notion that TGP molecules in
      cigarette smoke are absorbed systemically on smoking and may have a direct toxic
      effect when they attach to the surface TGP binding proteins of heart and skeletal
      muscle cells.

PMID- 7717871
TI  - Lectin binding pattern of Schwann cells and macrophages in 2,5-hexanedione
      induced axonal degeneration in rats.
AB  - The lectin binding pattern of both Schwann cells and macrophages has been studied
      during axonal degeneration induced in the rat sciatic nerve by chronic
      administration of 2,5-hexanedione (0.8 ml/kg per day i.p. for 20 days). In
      particular, the present study aimed to establish a possible relationship between
      macrophage activation and expression of lectin binding sites. To identify and
      distinguish between Schwann cells and macrophages, electron microscopy was
      combined with the lectin staining method. On 2,5-hexanedione injury, a drastic
      disorganization of both axon and myelin sheath occurred and nerve fibers were
      replaced by a chain of ovoids. Besides the well-established concept that Schwann
      cells and macrophages cooperate in the removal of the myelin debris during axonal
      degeneration, evidence is presented that expression of binding sites to lectins
      is closely related to macrophage activation. Monocytes occasionally present in
      control nerves were labelled only by Con A and sialidase-peanut sequence; in 2,5
      hexanedione degeneration monocytes, prephagocytes (macrophages with minute
      bubbles) and phagocytes (macrophages with large bubbles) were labelled also by
      peanut, wheat germ and BSA I-B4; moreover, phagocytes were labelled by soybean as
      well, thus showing a clearly differentiation-dependent binding pattern. Since
      changes in lectin binding pattern may reflect changes in complex carbohydrate
      structures, the results show that the expression of certain glycoproteins may be
      closely related to activation of macrophages in response to toxic injuries.

PMID- 7717872
TI  - Hepatotoxicity and P-4502E1-dependent metabolic oxidation of N,N
      dimethylformamide in rats and mice.
AB  - A comparative biochemical and histological study on the hepatotoxicity of a
      single dose of N,N-dimethylformamide (DMF) and N-methylformamide (NMF) in control
      and acetone-treated SD male rats and CD-1 male mice was performed. In control and
      acetone-pretreated rats, neither DMF nor NMF caused hepatic damage or elevation
      of plasma transaminases. In contrast, in acetonized but not in control mice, DMF
      administration yielded some evidence of liver necrosis and elevation of ALAT
      (alanine-amino transferase) activity. After a DMF dose of 1000 mg/kg, ALAT
      activity was found 1215 +/- 832 mU/ml and 47 +/- 18 mU/ml in acetonized and
      control mice, respectively. NMF treatment was hepatotoxic in control mice and
      lethal in acetonized mice. In control mice, an NMF dose of 600 mg/kg increased
      ALAT activity from a basal value of 35 +/- 5 to 2210 +/- 1898 mU/ml. When the
      oxidative metabolism of DMF was investigated, microsomes from both rats and mice
      preinduced by acetone increased the demethylation rate of DMF 7 to 10-fold
      compared to that (about 0.25 nmol/min per mg protein) of the corresponding
      control microsomes. The enzymatic affinities for DMF oxidation, however, were
      different: in mice the Km (0.05 mM) was one order of magnitude lower than that
      (0.56 mM) found in rats. The experiments performed with purified rat and mouse P
      450 2E1 in a reconstituted system confirmed that the P-450 2E1 isoforms are very
      active catalysts towards DMF oxidation (the turnover was about 10 nmol/min per
      nmol P-450 for both enzymes) but with a strikingly different affinity. Whereas
      the Km for mouse P-450 2E1 was 0.08 +/- 0.03 mM, that for rat P-450 2E1 was 1.1
      +/- 0.2 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717874
TI  - Dichloromethane as an inhibitor of cytochrome c oxidase in different tissues of
      rats.
AB  - Based on the metabolism of dichloromethane (DCM) to carbon monoxide (CO), a
      process mediated by cytochrome P-4502E1 (CYP2E1), cytochrome c oxidase activity
      was determined in different tissues of rats after DCM exposure. It is likely that
      binding of CO to cytochrome c oxidase is significant at low carboxyhemoglobin
      levels, because intracellular effects of CO depend on CO partial pressures in the
      tissues. Two methods of exposure were used: (1) administration of DCM, 3.1, 6.2,
      and 12.4 mmol/kg p.o. in Oleum pedum tauri, 10% (v/v), producing a maximum of 10%
      COHb 6 h after gavage, and (2) accidental scenario, i.e. rats were exposed nose
      only to DCM, 250,000 ppm for 20 s, producing 3-4% COHb after 2 h. Cytochrome c
      oxidase activity was reduced 6 h after the high oral DCM dose in brain, lung, and
      skeletal muscle by 28-42% and 20 min after inhalative uptake of DCM in the brain,
      liver, kidney, and skeletal muscle by 42-51%. COHb formation due to DCM, 6.2
      mmol/kg p.o., was completely prevented after treatment of rats with the mechanism
      based inhibitor of CYP2E1, diethyl-dithiocarbamate (DDTC), using an oral dose of
      32 mumol/kg. The decrease in cytochrome c oxidase activity after exposure to DCM
      was not evident in rats treated with this dose of DDTC. Therefore, it seems that
      the effect of DCM is produced by the DCM metabolite CO.

PMID- 7717873
TI  - Prostaglandin-H synthase mediated metabolism and mutagenic activation of 2-amino
      3-methylimidazo [4,5-f] quinoline (IQ).
AB  - Prostaglandin-H synthase (PHS), a mammalian peroxidase of interest for the
      extrahepatic formation of reactive intermediates of carcinogens, catalyzes in
      vitro the metabolic activation of the mutagen and carcinogen 2-amino-3
      methylimidazo-[4,5-f]quinoline (IQ). Incubation of 14C-labeled IQ with ram
      seminal vesicle microsomes (RSVM), a rich source of PHS, resulted in protein
      binding and generated products mutagenic in S. typhimurium YG1024. The mutagenic
      activity produced in IQ/PHS incubations was stable and extractable with ethyl
      acetate. Upon fractionation of such extracts by HPLC and subsequent analysis, two
      metabolites were identified as 2,2'-azo-bis-3-methylimidazo[4,5-f]quinoline (azo
      IQ) and 3-methyl-2-nitro-imidazo[4,5-f]quinoline (nitro-IQ) confirmed by
      comparison of HPLC retention times, UV/VIS-, 1H-NMR-spectroscopy, and mass
      spectrometry of synthesized standards. Azo-IQ was obtained by chemical oxidation
      of IQ with meta-sodium periodate. It was the major metabolite in PHS incubations,
      but has not been detected in monooxygenase incubations. Azo-IQ, without metabolic
      activation, was much less mutagenic in S. typhimurium YG1024 (308 rev/nmol) than
      nitro-IQ and 3-methyl-2-nitroso-imidazo[4,5-f]quinoline (nitroso-IQ), two other
      S9-independent mutagens which have been synthesized by chemical oxidation of IQ
      with sodium nitrite. Nitro-IQ was formed only in trace amounts but due to its
      potent mutagenicity in S. typhimurium YG1024 (2 x 10(6) rev/nmol) it accounted
      for most of the mutagenic activity of the incubations. These data show that PHS
      mediated in vitro metabolism of IQ results in its metabolic activation; thus PHS
      may contribute to the genotoxicity of IQ in extrahepatic tissues.

PMID- 7717875
TI  - Effect of cytochrome P450 isozyme induction and glutathione depletion on the
      metabolism of CS2 to TTCA in rats.
AB  - Analysis of 2-thiothiazolidine-4-carboxylic acid (TTCA), a metabolite of carbon
      disulfide (CS2), is used in the biological monitoring exposure to CS2 at work. In
      order to clarify the metabolic reasons for individual variation in the urinary
      excretion of TTCA, the latter was studied in rats pretreated with model
      cytochrome P450 (CYP) enzyme inducers or glutathione (GSH) depletors. Ethanol,
      phenobarbital (PB) or 3-methylcholanthrene (MC) did not increase 24-h TTCA output
      following CS2 inhalation (50 or 500 ppm, 6h). After oral dosing (10 mg/rat), PB
      had an inhibiting effect on the excretion rate of TTCA. Tissue GSH depletors
      phorone, L-buthionine-(RS)-sulfoximine (BSO) and diethylmaleate (DEM) decreased
      TTCA excretion in rats given an oral dose (10 mg/rat) of CS2. The initial
      inhibition by phorone and DEM was reversed after 6 h and from 12 h onward the
      TTCA in urine exceeded the control level, an effect not seen with BSO. The
      proportion of CS2 excreted in urine as TTCA within 24 h was 1.7% in control rats
      and 1% after BSO treatment, 1.3% after PB, 1.7% after acetone, 1.8% after MC,
      2.0% after phorone and 2.5% after DEM treatment. The amount of TTCA in urine
      increased with the CS2 dose in a non-linear fashion: 1.6 mumol (50 ppm/6 h) vs.
      4.9 mumol (500 ppm/6 h), and 0.2 mumol (1 mg/kg) versus 3.6 mumol (100
      mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717877
TI  - Stimulation of myosin light-chain kinase by Cd2+ and Pb2+.
AB  - The effect of Cd2+ on myosin light chain kinase (MLCK) reported in the literature
      is controversial, apparently because the level of Ca2+ contaminating the reaction
      mixture could not be accurately controlled by the addition of a metal chelator
      when Cd2+ was also present. In the present study, we have reduced the
      contaminating Ca2+ to a trace level that did not interfere with the enzyme
      activity; thus the use of a metal chelator was not necessary. We showed that
      Cd2+, or Pb2+ had a biphasic effect on MLCK isolated from chicken gizzard:
      stimulation at low and inhibition at high concentrations. (The stimulatory effect
      of on the enzyme activity isolated from chicken gizzard: stimulation at low and
      inhibition at high concentrations). The stimulatory effect of Cd2+ or Pb2+ on
      MLCK activity was not seen in the absence of calmodulin, and was abolished by
      trifluoperazine, a calmodulin antagonist, indicating that the heavy metals exert
      their activation via calmodulin. The inhibition of the enzyme activity by Cd2+ or
      Pb2+ at higher concentrations was also seen with the calmodulin-independent
      catalytic fragment of MLCK, suggesting that the inhibition is probably through
      their binding to sulfhydryl groups that are essential for catalytic activity.
      Pb2+ was more effective than Cd2+ in stimulating the enzyme activity, but less
      potent in inhibition. The extent of stimulation by heavy metals most likely
      resulted from a combination of the biphasic effects. Dithiothreitol and N,N,N',N'
      tetrakis (2-pyridylmethyl) ethylenediamine selectively chelated Cd2+ and Pb2+
      over Ca2+, and reversed their stimulatory or inhibitory effect on MLCK.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7717876
TI  - Effects of inorganic mercury (Hg2+) on calcium channel currents and catecholamine
      release from bovine chromaffin cells.
AB  - The effects of inorganic mercury (Hg2+) on calcium channel currents and the
      potassium-evoked catecholamine release of bovine chromaffin cells in culture were
      examined. The effects of cadmium (Cd2+), known to block calcium channels and
      reduce catecholamine release of chromaffin cells, were studied for comparison.
      Calcium channel currents were recorded in the whole-cell configuration of the
      patch-clamp technique. Hg2+ is a potent calcium channel blocker in bovine
      chromaffin cells. The IC50 value is about 3 microM, the Hill slope 1.46. In a
      concentration of 100 microM, Hg2+ blocked the currents completely; 100 microM
      Cd2+ had the same effect. Potassium-evoked catecholamine release from chromaffin
      cells was measured at different time-points with high-performance-liquid
      chromatography (HPLC) under control conditions and in the presence of different
      Hg2+ concentrations. Low Hg2+ concentrations (0.1 and 1 microM) did not affect
      the amount of the catecholamines epinephrine (E) and norepinephrine (NE) which
      was released. Under identical conditions 1 microM Cd2+ also had no effect on
      release. With 10 microM Hg2+ there was a time-dependent increase in the potassium
      evoked catecholamine release (by 27% after 8 min). The E/NE ratio was not
      altered, suggesting that the release of both hormones was increased similarly. In
      contrast to this, the release was slightly reduced with 10 microM Cd2+. In the
      presence of 100 microM Hg2+, there was a reduction of the release during an early
      phase, followed by an increase. The reduction is most probably due to the fast
      and effective calcium channel block by Hg2+ in this high concentration.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7717878
TI  - Cytotoxicity of propyl gallate and related compounds in rat hepatocytes.
AB  - The cytotoxic effects of propyl gallate (PG), its related gallates and gallic
      acid have been studied in freshly isolated rat hepatocytes. Addition of PG (0.5
      2.0 mM) to hepatocyte suspension elicited concentration-dependent cell death
      accompanied by losses of intracellular ATP, adenine nucleotide pools, glutathione
      (GSH) and protein thiols. The rapid loss of intracellular ATP preceded the onset
      of cell death caused by PG. In the comparative toxic effects of PG and related
      gallates at concentration of 1 mM, octyl gallate (OG), dodecyl gallate (DG) and
      butyl gallate (BG) elicited an abrupt depletion of ATP, followed by an acute cell
      death. These gallates were more toxic than PG; the toxic effects of PG were
      similar to those of methyl gallate (MG) and ethyl gallate (EG). In mitochondria
      isolated from rat liver, PG caused a concentration-dependent increase in the rate
      of state 4 oxygen consumption, indicating an uncoupling effect. The rate of state
      3 oxygen consumption was inhibited by OG and DG. According to the respiratory
      control index, the order of impairment potency to mitochondria was OG > BG, DG >
      PG > EG, MG > gallic acid. These results indicate that PG and related gallates
      are toxic to hepatocytes and that the acute cytotoxicity may be due to
      mitochondrial dysfunction.

PMID- 7717879
TI  - The detection of subchronic testicular damage using urinary creatine: studies
      with 2-methoxyethanol.
AB  - We have previously shown that a number of testicular toxicants administered
      acutely to rats raise urinary creatine. The aim of this study was to determine if
      this creatinuria was maintained during subchronic testicular damage. Repeated
      exposure of rats to 2-methoxyethanol for 10 days administered in the drinking
      water caused significant testicular damage at the highest dose. The urinary
      creatine:creatine ratio was significantly increased in the animals receiving the
      highest dose (220 mg/kg per day) and also those receiving doses of 87 mg/kg per
      day. Increases in the ratio seen after the lowest dose (43 mg/kg per day) were
      significant in some cases, but showed more variability. Relative testicular
      weight was only significantly reduced after the highest dose. Increases in body
      weight over the time of exposure were only significantly lower after the highest
      dose of 2-methoxyethanol. The results indicate that urinary creatine may be a
      useful biomarker for chronic testicular damage.

PMID- 7717880
TI  - Difference in rates of the reaction of various mammalian oxyhemoglobins with
      phenylhydrazine.
AB  - Second order rate constants for the initial reaction of 12 mammalian
      oxyhemoglobins (Hb) with equimolar phenylhydrazine (PHZ), a compound inducing
      Heinz body hemolytic anemia, were determined by recording continuous changes in
      absorbance with time at 577 nm. The rate constants were varied in a range from 43
      m-1.s-1 with pig Hb to 255 m-1.s-1 with dog Hb. On the other hand, isosbestic
      points at 526 and 587 nm were common to all the reaction processes. The aerobic
      reaction of Hb with PHZ resulted in denaturation of hemoprotein, and final
      reaction products were determined to be beta-meso-phenylbiliverdin IX alpha and N
      phenylprotoporphyrin IX. These results suggest that the reactivity of PHZ to Hb
      is influenced by the globin molecule, and the oxidative cleavage of the porphyrin
      ring causes the denaturation of hemoprotein.

PMID- 7717882
TI  - Biometric analysis of tooth migration after approximal contact removal in the
      rat.
AB  - Nineteen 8-week-old female Sprague-Dawley rats were used to observe
      macroscopically the direction of tooth movements following removal of approximal
      contacts. In 10 rats, under anaesthesia, approximal contact between the second
      and third right maxillary molars (M2-M3) was removed by grinding. These animals
      and a control group of nine rats were housed with normal diet and water ad
      libitum for 7 weeks. After killing, the skulls of all animals were removed,
      dried, and fixed in a standardized position on a Horsley-Clarke type stereotaxic
      frame. Using a micromanipulator graduated to 1/100 mm and mobile in three
      orthogonal directions, distances between the teeth (M1 or M3) and some bone
      structures that served as landmarks were measured. These measurements showed the
      direction of tooth movements in the experimental approximal space. After
      statistical analysis of the data, the results showed that the approximal space
      between M2 and M3 was closed by both a distal drift of M1-M2 and a mesial
      migration of M3. It was concluded that, in the rat, a mesial drift exists that
      can be induced by the loss of approximal contact. This movement is distinct from
      the distal physiological dental migration classically described in histological
      studies.

PMID- 7717881
TI  - cDNA cloning, sequencing and in situ localization of a transcript specific to
      both sublingual demilune cells and parotid intercalated duct cells in mouse
      salivary glands.
AB  - A cDNA clone derived from mouse sublingual gland was isolated from lambda-phage
      cDNA library. Northern blot hybridization indicated that the transcript from
      which it was derived was approx. 700 nucleotides in length. This mRNA encoded a
      protein of about 20 kDa, as determined by hybrid selection and cell-free
      translation. Conceptual translation of the cDNA clones showed that p20 is 170
      amino acids in length. The putative protein is hydrophobic in nature, is neither
      a mucin-like protein nor does its amino acid sequence or composition resemble the
      other known mouse proteins. However, the amino acid sequence of p20 suggests that
      it may be from a gene or gene family homologous to rat common salivary protein 1.
      The p20 mRNA also appears to share a non-random degree of sequence homology with
      the cysteine-rich domains of bovine and porcine submandibular mucins. The p20
      mRNA is abundant in the mouse sublingual gland, and its expression is approx.
      nine times greater than in the parotid gland. In situ hybridizations localized
      the p20 mRNA exclusively in the demilune cells of the sublingual gland and in the
      intercalated duct cells of the parotid gland. It is detectable in the neonatal
      and adult submandibular gland at very low levels, but is absent from liver,
      heart, brain, thymus, spleen, lens and lacrimal glands.

PMID- 7717883
TI  - A method for measuring the structural properties of the rat mandible.
AB  - The rat mandible has been used to study fractures, ridge augmentation, bone
      defects, and the effects of cryosurgery, all of which affect the structural
      properties of the mandible. The only previously described mechanical test of the
      rat mandible used three-point bending with a piece of foam placed between the
      lingual surface of the mandible and the support. The accuracy and reproducibility
      of this test were not determined. Two different, three-point bending tests for
      characterizing the structural properties of the rat mandible have now been
      evaluated. Acrylic specimens representing three different-sized mandibles were
      tested in three-point bending with either potted ends or foam interposed between
      the specimen and the outer load points. Flexural stiffness and failure load were
      compared against data from a conventional three-point bending test. In addition,
      five paired halves of 90- and 210-day-old rat mandibles were tested either with
      interposed foam or with potted ends and the mean coefficients of variation of the
      stiffness and failure loads were determined. Failure loads of the acrylic
      specimens with the potted and foam methods were significantly higher (50 and 10%,
      respectively; p < 0.05) than with the conventional method. The stiffness of the
      acrylic specimens with the potted and foam methods was significantly different
      (75% higher and 21% lower, respectively; p < 0.05) than with the conventional
      test. In addition, there was no difference between the coefficient of variation
      in stiffness (26 + 11%) or failure load (10 + 4%) measured with the foam test and
      the comparable values (16 + 11%) and (18 + 13%) in the potted test.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7717884
TI  - Oral infection with Porphyromonas gingivalis and induced alveolar bone loss in
      immunocompetent and severe combined immunodeficient mice.
AB  - The suitability of a mouse model for host response in the induction of alveolar
      bone loss by Porphyromonas gingivalis was explored. The mouths of immunocompetent
      and severe combined immunodeficient (SCID) mice were infected with P. gingivalis
      ATCC 53977. P. gingivalis was not isolated from the mouths of these mice before
      infection, but was present at least 42 days after infection. P. gingivalis
      specific IgG was present in sera from the infected, immunocompetent mice at the
      end of these experiments (42 days). Specific IgG was not present in sham-infected
      or uninfected immunocompetent mice, nor in any immunodeficient mice. Specific IgM
      was not present in any sera at 42 days. Infected, immunocompetent mice of two
      strains showed significant bone loss in comparison to sham-infected or uninfected
      immunocompetent mice (p < 0.05). Infected SCID mice, which are genetically
      lacking both B and T lymphocytes, also showed significant bone loss compared with
      sham-infected or uninfected SCID mice (p < 0.05). However, the degree of bone
      loss was greater in immunocompetent than immunodeficient mice: the relative
      amount of bone in infected mice was 77% of that in sham-infected immunocompetent
      mice, and 86% of sham values in SCID mice (p = 0.025). Thus oral infection of
      mice is a feasible model for studying the effects of host response on P.
      gingivalis-induced alveolar bone loss. Because bone loss was induced both in
      immunocompetent and SCID mice but was greater in immunocompetent mice, it appears
      that neither B nor T cells are absolutely necessary for bone resorption in
      response to P. gingivalis infection but they may significantly modulate the
      degree of resorption.

PMID- 7717885
TI  - The effects of anti-nerve growth factor on retrograde labelling of superior
      cervical ganglion neurones projecting to the molar pulp in the rat.
AB  - The aims were to demonstrate sympathetic ganglion neurones projecting to the rat
      molar pulp and to determine whether deprivation of nerve growth factor (NGF) in
      neonatal rats eliminates this source of pulpal innervation. Newborn Sprague
      Dawley rats were given subcutaneous injections of rabbit anti-mouse-NGF serum for
      1 month. Control animals included litter mates treated with preimmune serum and
      untreated, age-matched rats. AT 4 months of age, Fluoro-gold (FG) was applied to
      the pulp chamber of the right first maxillary molar. One week later, the animals
      were perfusion fixed, and the superior cervical ganglia (SCG) were removed,
      embedded in paraffin, and serially sectioned at 10 microns. FG-labelled cells
      were detected by epifluorescence microscopy with a u.v. filter set. Control
      animals had 5-10 FG-labelled neurones widely distributed throughout the SCG
      ipsilateral to the injection site and no labelled cells in the contralateral SCG.
      NGF-deprived animals had either no FG-labelled cells or a single labelled cell in
      the ipsilateral SCG. These results indicate that, in rats, (1) the number of SCG
      neurones projecting to the molar pulp is rather low, (2) SCG neurones that
      innervate the dental pulp of the maxillary molar pulp are dispersed throughout
      the ganglion, (3) the projection from SCG to the molar is exclusively
      ipsilateral, and (4) neonatal NGF deprivation induces a permanent, almost total,
      loss of sympathetic neurones projecting to the dental pulp.

PMID- 7717886
TI  - Immunocytochemical localization of cathepsin L in the synovial lining cells of
      the rat temporomandibular joint.
AB  - Localization of cathepsin L in the synovial lining cells of the normal rat
      temporomandibular joint was investigated by the avidin-biotin-peroxidase complex
      method for semithin (1 microns) cryosections and the colloidal gold-labelled IgG
      method for ultrathin sections of LR gold resin. At the light-microscopic level,
      type A (macrophage-like) and B (fibroblast-like) cells formed the synovial lining
      layer. Extensive immunoreactivity for cathepsin L was observed in many granules
      and vacuoles of type A cells, while in the type B cells, immunoreactivity was
      found in very few granules. In the sublining layer, macrophages and a few
      fibroblasts were positive for cathepsin L. By electron microscopy, at the
      peripheral cytoplasm of the type A cells close to the lateral intercellular
      spaces and joint cavity, numerous coated vesicles and vacuoles (probably early
      endosomes) indicating endocytotic function were found. Gold particles indicating
      cathepsin L were localized in the vesicles (primary lysosomes) in the perinuclear
      cytoplasm and in the larger amorphous vacuoles (1 microns dia) as phagolysosomes.
      In type B cells, gold particles were limited to the vesicles only (primary
      lysosomes). The cathepsin L-positive primary lysosomes were numerous in a few
      fibroblasts in the sublining layer. These results indicate that type A cells
      contain a large amount of cathepsin L, and suggest that these cells endocytose
      surplus substances such as collagen and proteoglycan fragments in normal rat TMJ,
      effecting their digestion and degradation by the action of this proteolytic
      cathepsin.

PMID- 7717887
TI  - Colonization by mutans streptococci in the mouths of 3- and 4-year-old Chinese
      children with or without enamel hypoplasia.
AB  - This case-control study compared the prevalence and concentration of mutans
      streptococci (MS) in saliva between children with and without enamel hypoplasia
      (EHP). A total of 486 3- or 4-year-old Chinese children were initially screened
      for EHP, then distributed into two groups: 234 children diagnosed as having EHP
      were assigned to the case group; 252 who were free of EHP were included in the
      control group. The concentration of MS in saliva was assayed for each child.
      Nutritional status was deduced from body height and weight. Birth weight,
      prematurity, and nursing history were also determined. MS were found in 94.7% of
      the study population. The differences in MS concentrations were not associated
      with low birth weight, prematurity, length of breast feeding, or body height and
      weight. A statistically significant association existed between the presence of
      EHP and high counts of MS (p < 0.001). High MS counts were correlated with
      severity of enamel defects (p < 0.001). When the caries status of the children
      was controlled as the confounding factor in statistical analyses, the association
      between EHP and MS decreased but still remained significant (p = 0.025). This
      study shows that high MS counts are correlated with EHP, suggesting that
      irregularities in enamel surfaces could be a contributing factor that fosters the
      increased colonization of MS in the mouths of children.

PMID- 7717888
TI  - The effect of milk and casein proteins on the adherence of Streptococcus mutans
      to saliva-coated hydroxyapatite.
AB  - Experiments sought to determine the nature of the binding of milk proteins to
      hydroxyapatite (HA) and to saliva-coated hydroxyapatite (sHA), and to determine
      the effect of milk and casein on the adherence of Streptococcus mutans GS-5 to
      sHA. The binding of radiolabelled alpha-casein to HA was reduced when incubated
      simultaneously with parotid saliva, and enhanced in the presence of milk. The
      binding of beta- and kappa-casein to HA was unaffected by the presence of parotid
      saliva and enhanced by the presence of milk. The in vitro bacterial adherence of
      Strep. mutans GS-5 to sHA beads was reduced when beads were coated with milk
      instead of buffer, or when bacteria were added to sHA in the presence of milk
      instead of buffer. Casein proteins (alpha, beta, kappa) added to sHA
      simultaneously with bacteria inhibited the adherence of Strep. mutans GS-5 to
      sHA. kappa-Casein, when bound to sHA, inhibited streptococcal adherence to sHA;
      alpha- and beta-casein, when bound to sHA, had no effect on streptococcal
      adherence. Fractionation of kappa-casein by anion-exchange chromatography
      revealed the anti-adherence activity of kappa-casein was mediated primarily by a
      40,000 mol. wt. glycoprotein-containing fraction. These data show that milk,
      particularly kappa-casein fractions, can modulate the adherence of Strep. mutans
      GS-5 to SHA surfaces in vitro.

PMID- 7717889
TI  - Spatial distribution of endogenous retinoids in the murine embryonic mandible.
AB  - Retinoids play an important part in pattern formation during embryonic
      development. Exogenous retinoids alter the pattern of skeletal, neural and
      odontogenic tissues. Endogenous retinoids have been demonstrated previously in
      the murine embryonic mandible, reaching a concentration peak during the
      initiation of odontogenesis. It was now found that endogenous retinoids are
      present in a concentration gradient in the embryonic mouse mandible at the time
      of the initiation of the dental lamina. All-trans-retinoic acid was more
      concentrated in the incisor region and retinol in the molar region. These
      results, and the fact that exogenous retinoids produce supernumerary incisors and
      missing molars, suggest that all-trans-retinoic acid may instruct incisor
      morphology.

PMID- 7717890
TI  - A comparison of human masseter muscle thickness measured by ultrasonography and
      magnetic resonance imaging.
AB  - Non-invasive imaging techniques such as computerized tomography, magnetic
      resonance imaging (MRI), and ultrasonography enable measurements of the cross
      section and thickness of human jaw muscles in vivo, providing an indication of
      the maximal force a muscle can exert. In 15 adult Caucasian men the thickness of
      the masseter muscle was registered bilaterally on three different levels by
      ultrasonography. Scans were made on the contracted and relaxed muscle. A
      comparison was then made with measurements from serial MRI scans, using
      univariate analysis of variance for repeated measurements and Pearson's
      correlation coefficients. Variances of the repeated measurements were calculated
      for the different scanning levels and the different muscle conditions and tested
      for homogeneity. For both the ultrasound and MRI measurements there was no
      difference in thickness between the left and right muscle. The registration level
      with highest reproducibility was halfway between the origin and insertion.
      Measurements from the contracted muscle were more reproducible than those from
      the relaxed muscle. The relaxed muscle thickness measured by ultrasonography was
      smaller than that measured by MRI. The correlation between ultrasound and MRI was
      significant for the upper and middle level of scanning (p < 0.001). The highest
      correlation was found between MRI (relaxed) and ultrasound (contracted) at the
      middle level (R = 0.83, p < 10(-6)). The conclusion is that ultrasonography is an
      accurate and reproducible method for measuring the thickness of the masseter in
      vivo. It allows for large-scale longitudinal study of changes in jaw-muscle
      thickness during growth in relation to change in biomechanical properties of
      masticatory muscles.

PMID- 7717892
TI  - Influenza vaccination: reaching those at risk.

PMID- 7717893
TI  - A diabetes PA activity--Part 2.

PMID- 7717891
TI  - Induction of dentine in amputated pulp of dogs by recombinant human bone
      morphogenetic proteins-2 and -4 with collagen matrix.
AB  - Recombinant human bone morphogenetic protein (BMP)-2, BMP-4 and transforming
      growth factor (TGF)-beta 1 combined with collagen matrix as a carrier were
      examined for their effects on pulp regeneration and dentine formation. Seventy
      days after implantation of 2 micrograms of BMP-2, mineralized osteodentine-like
      tissue containing embedded osteodentinocytes was seen in the cavity.
      Unmineralized fibrous tissue and pulp-like loose connective tissue were also
      found in the same cavity. In teeth implanted with 660 ng of BMP-2 only
      unmineralized fibrous and pulp tissues were seen. In teeth with 220 ng of BMP-2
      or collagen alone, pulp tissue was seen. It is therefore likely that the cavity
      fills with pulp tissue and that spindle-shaped cells elaborate extracellular
      matrix that mineralizes to be osteodentine in a dose-dependent manner. Similar
      osteodentine was seen in teeth implanted with 4 micrograms of BMP-4 and collagen.
      No distinct tubular dentine was formed, unlike an earlier experiment in which BMP
      2 or -4 was implanted with enriched, inactivated dentine matrix. These findings
      suggest that both BMP-2 and -4 induce osteodentine formation if combined with
      collagen matrix; some other matrix component present in inactivated dentine
      matrix might be essential for further differentiation into odontoblasts. In teeth
      implanted with TGF-beta 1, the carrier collagen remained in the cavity and little
      pulp tissue proliferation was seen, suggesting a possible inhibitory effect of
      TGF-beta 1 in pulp regeneration. It is likely that the response to growth and
      differentiation factors is dependent on the state of differentiation of pulp
      cells.

PMID- 7717894
TI  - Hepatitis C: a current perspective.
AB  - This article covers several dilemmas posed by hepatitis C for the family
      physician. It is proposed that patients with known risk factors, such as
      injecting drug use or blood transfusion, be treated for an anti HCV. The problems
      of counselling the patient with an incidental positive anti HCV test are
      discussed; at present, the history of risk factors and liver test results are the
      most important aspects as there is no gold standard for hepatitis C diagnosis.
      Family and sexual transmission of HCV are rare; only mothers with extremely high
      levels of HCV viraemia are likely to transmit HCV to their offspring. Decisions
      about interferon treatment for hepatitis C require consideration of the natural
      history of this disease, the chances of a long-term response to treatment, and
      the adverse affects of interferon. Screening for hepatocellular carcinoma is
      proposed for patients who already have cirrhosis.

PMID- 7717896
TI  - Hepatomegaly: causes and consequences.
AB  - Many steps in the diagnostic workup of the patient with liver disease or surgical
      jaundice can be taken by the general practitioner with subsequent referral on to
      a gastroenterologist or surgeon to complete the diagnostic process. The principal
      objective in patients with parenchymal liver disease is to make an early
      diagnosis and initiate early treatment so that progression to cirrhosis and its
      complications can be avoided. Maintaining an awareness and knowledge of the
      various symptoms and signs of liver disease will aid in this objective.

PMID- 7717895
TI  - Management of the chronic hepatitis B carrier.
AB  - Chronic hepatitis B is an increasingly prevalent disease in Australia, both
      because of inadequacies of the current vaccination program, and because of
      changing population demographics. Regular follow-up of these patients is
      indicated, particularly as we now have effective anti viral therapy available.
      The unfavourable disease outcome in about 30% of hepatitis B carriers warrants
      increased recognition and observation of this group of patients.

PMID- 7717897
TI  - Jaundice: a clinical perspective.
AB  - The correct diagnosis in a jaundiced adult suggests itself clinically. A logical
      approach will avoid inappropriate tests, delays in diagnosis and unnecessary
      hospitalisation.

PMID- 7717898
TI  - Ultrasound and liver disease.
AB  - The widespread availability of ultrasound has revolutionised the investigation of
      hepatobiliary disease. Liver ultrasound should be the primary imaging modality in
      jaundice, suspected diffuse liver disease or focal liver disease and supplemented
      by other modalities where indicated. The advent of Duplex and Colour Doppler
      imaging has expanded the utility of ultrasound techniques in relation to the
      hepatic vasculature. This article presents an overview of the use of ultrasound
      in liver disease.

PMID- 7717899
TI  - Liver transplantation: a decade later.
AB  - Liver transplantation is now a major consideration in the management for end
      stage chronic liver disease. The author outlines the advances in the procedure
      over the past 10 years, surveys the diseases corrected or stabilised by it and
      looks ahead to the next 10 years.

PMID- 7717901
TI  - A guide to strategic planning.
AB  - Strategic planning is a new concept in general practice. Underneath all the
      jargon, however, it is simply a label for the planning and evaluation processes
      that most organisations have used in the past. The aim of this paper is to
      demystify strategic planning as it applies to newly formed Divisions of General
      Practice.

PMID- 7717900
TI  - The management of male subfertility by in vitro fertilisation techniques.
AB  - Although IVF was developed for the treatment of tubal infertility, it is clear
      that it has a significant application in treatment of couples where the problem
      is one of male subfertility. This is particularly relevant because, despite the
      developments in reproductive medicine, in most males there is no identifiable
      cause for the poor semen quality. Therefore, for these men there is no
      efficacious method of treatment. Varicocele ligation and the use of agents such
      as clomiphene citrate, mesterolone empirical antibiotic therapy, and anabolic
      steroids have not been show to be beneficial when subject to controlled trials.
      The concept of improving the chance of fertilisation by taking the oocytes to the
      sperm in vitro is therefore the first feasible therapeutic option available to
      these subfertile couples. However, these possibilities should not obviate the
      need for a thorough assessment of the subfertile male and continuing research
      into the basis of male infertility. During the past decade new methods of sperm
      preparation, modified methods of insemination, and the use of microinjection have
      been developed. IVF is now a realistic option for couples if the male is
      subfertile. It has been suggested by some critics of these techniques that the
      brunt of the discomfort and risk has to be borne by the women where the problem
      appears to be solely with the male partner. Nevertheless, as having children is a
      'couple' decision, prospective couples need to consider whether such procedures
      are acceptable to them.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7717902
TI  - Confidentiality in general medicine and police service medicine.
AB  - Confidentiality in medical practice is a complex matter. This is because of the
      uniqueness of each doctor-patient relationship. The availability of guidelines
      assists when a more formal direction needs to be established. Doctors should
      remember that the most specific advice will come from their medical protection
      society and they should seek this if they have any doubts. A patient's secrets
      are theirs and theirs alone. Generally, a doctor can divulge them only with his
      or her patient's permission.

PMID- 7717903
TI  - Changes to recommended immunisation procedures.
AB  - The fifth edition of the Australian Immunisation Procedures Handbook updates what
      has become an important reference and practical guide to immunisation practice in
      Australia. A number of significant changes have been incorporated into this
      edition. The purpose of this paper is to alert and remind general practitioners
      of these changes.

PMID- 7717904
TI  - Menopause: its management in general practice.
AB  - Menopause is managed in over 10% of general practice consultations with women
      aged between 45 and 54 years, yet there is little information about its
      symptomotology and its management by GPs. This paper investigates these issues in
      a secondary analysis of data from the Australian Morbidity and Treatment Survey
      1990-1991.

PMID- 7717905
TI  - Herpes simplex: treatment options.

PMID- 7717906
TI  - Signs and symptoms in drug addiction.

PMID- 7717907
TI  - Edwin Walter Knight. Media doctor and author.

PMID- 7717908
TI  - Critical assessment of ACE inhibitors. Part 1.
AB  - Critical assessment of ACE inhibitors is an independent review of an important
      group of drugs widely used in the management of hypertension and heart failure.
      The paper is presented in two parts: Part 1 contains an overview of their action
      and their use in the treatment of hypertension. Part 2 focuses on the use of ACE
      inhibitors in heart failure and in pregnant women and in children.

PMID- 7717909
TI  - Shoulder tip 'tips'.

PMID- 7717910
TI  - Patient education. Sprained ankle.

PMID- 7717911
TI  - Acute gout in the great toe.

PMID- 7717912
TI  - Acute chest pain.

PMID- 7717913
TI  - Chronic pain.

PMID- 7717914
TI  - Euthanasia and ethics.

PMID- 7717915
TI  - Topical anaesthesia for children's lacerations.

PMID- 7717916
TI  - Tuberculosis: a global emergency.

PMID- 7717917
TI  - A brave new world of cancer screening.

PMID- 7717918
TI  - Bedding and childhood asthma.

PMID- 7717919
TI  - Direct mutational analysis in a family with hereditary non-polyposis colorectal
      cancer.
AB  - BACKGROUND: It is now known that a proportion of cases of hereditary non
      polyposis colorectal cancer (HNPCC) is caused by mutations in the human homologue
      of the yeast DNA mismatch repair gene MSH2. A proline to leucine change due to a
      C to T transition in codon 622 of hMSH2 has been identified in a large HNPCC
      family of over 240 individuals. AIM: To develop an assay to detect the family
      specific mutation and apply the findings to genetic screening. METHODS: The C to
      T change in codon 622 creates a new Mae I site (CTAG) allowing a simple, non
      radioactive assay to be developed in order to detect this mutation. The assay was
      applied to affected members of the family and their first degree relatives
      (siblings and offspring) between the ages of 17 and 77 years, a total of 75
      subjects within two generations (IV and V). RESULTS: 13/13 (100%) subjects with
      cancer were mutation positive, 7/7 (100%) elderly subjects from generation IV and
      with no evidence of cancer were mutation negative, 23/57 (40%) subjects from
      generation V were mutation positive and 0/50 (100%) unrelated subjects were
      mutation negative. Following the demonstration of perfect segregation of the
      disease with the mutation, family members were invited to receive the results of
      the test. Sixty-three (84%) responded within six weeks of receiving the
      invitation. Genetic screening and counselling members of HNPCC families was
      perceived as beneficial overall, allowing non-carriers of the mutant gene (as
      well as their descendants) to be removed from a programme of colonoscopic
      surveillance.

PMID- 7717921
TI  - A pseudoepidemic of Mycobacterium chelonae: contamination of a bronchoscope and
      autocleaner.
AB  - BACKGROUND: At fibreoptic bronchoscopy the potential exists for contamination of
      bronchoscopes and microbiological specimens. Patients may also be cross infected
      with acid fast bacilli (AFB). During a five month period, 12 bronchial wash
      specimens of 65 patients undergoing bronchoscopy, one bronchoscope and an
      autocleaner, were contaminated with the AFB, Mycobacterium chelonae (MCH). AIM:
      To eradicate AFB contamination of bronchoscopy specimens by identifying sources
      of contamination and modifying disinfection procedures. METHODS: To identify the
      source of contamination, samples for AFB culture were taken from three
      bronchoscopes, the autocleaner and water taps. To eradicate MCH contamination,
      the bronchoscopes were soaked in 2% glutaraldehyde overnight and flushed with 70%
      alcohol. Disinfection procedures were altered by using sterile water and
      containers in cleaning. Autocleaner use was discontinued. RESULTS: The
      autocleaner, one bronchoscope and 12 bronchial wash specimens were contaminated
      with MCH. All contaminants had similar electrophoretic banding on probing of
      their DNA fragments, suggesting a common clone of origin. After the alterations
      in disinfection procedures and despite prolonged soaking in 2% glutaraldehyde,
      three further contaminated wash specimens were isolated from one bronchoscope.
      Only after ethylene oxide sterilisation of this bronchoscope was the
      contamination overcome. Since then no further MCH contamination has occurred. No
      patient required treatment and there has been no clinical evidence of
      mycobacterial disease. CONCLUSION: To avoid contamination of bronchoscopy
      specimens with MCH, use of autoclearners should be discouraged and sterile water
      and containers used in cleaning procedures. If MCH contamination occurs in this
      setting, the bronchoscope and dismantled valve mechanism should undergo ethylene
      oxide sterilisation.

PMID- 7717920
TI  - Sheepskins and bedding in childhood, and the risk of development of bronchial
      asthma.
AB  - BACKGROUND: Sheepskin bedding might increase house dust mite exposure and so
      explain some of the increasing prevalence of severity of childhood asthma.
      METHODS: Relationships between use of different types of bedding, and diagnoses
      of asthma, symptoms of wheezing, skin prick test evidence of house dust mite
      sensitivity, and airway responsiveness to methacholine, were examined
      retrospectively in a birth cohort of children followed longitudinally to age 15
      years. RESULTS: In the whole cohort, no associations were identified to suggest a
      causal relationship between use of any type of bedding and development of
      features of asthma. Although not an a priori hypothesis, we noted that among
      children with a family history of atopic disease, those who were house dust mite
      sensitive were more likely to have used an innerspring mattress (29.6% vs 10.2%
      who had not used an innerspring mattress, p = 0.005). CONCLUSION: In this
      subgroup, increased airway responsiveness and mite sensitivity were significantly
      associated with use of innerspring mattresses, although whether this is a causal
      or secondary association is not certain. Use of a sheepskin in the bed in early
      childhood was not an additional risk factor for the development of asthma.

PMID- 7717922
TI  - Trends in the incidence of end-stage renal failure due to hypertension and
      vascular disease in Australia, 1972-1991.
AB  - BACKGROUND: Despite the known protective effects upon renal function of lowering
      blood pressure in primary chronic renal disease, diabetes and malignant
      hypertension, the number of patients entering dialysis and transplantation
      programmes with renal failure due to hypertension or vascular disease remains
      high. AIMS: To analyse the trends in incidence of arteriopathic end-stage renal
      failure. METHODS: Calculation of mean annual age- and sex-specific rates (by
      decade) and truncated age-standardised rates for entry into Australian end-stage
      renal failure programmes in the period 1972-1991. Statistical analysis by chi
      squared test, assuming a Poisson distribution of cases. RESULTS: End-stage renal
      failure attributed primarily to hypertension or vascular disease fell to less
      than half its former level over the period of observation in persons aged 15-54
      years. This change has occurred only in the diagnostic category 'malignant
      hypertension'. Trends in persons aged 55 years and over are more difficult to
      analyse because of changing criteria for entry into renal failure programmes, but
      there has been no indication of any fall in incidence. CONCLUSIONS: The aetiology
      and pathology of arteriopathic renal failure is diverse, with different patterns
      in young and old adults. The formerly common pathology in young adults is largely
      preventable by modern antihypertensive therapy, while arteriopathic renal disease
      in older persons is not.

PMID- 7717923
TI  - Bone presentation of non-Hodgkin's lymphoma: experience at the Royal North Shore
      Hospital, Sydney; highlighting primary bone lymphoma.
AB  - BACKGROUND: Primary lymphoma of bone (PLB) is a rare form of extranodal lymphoma.
      Between 1975 and 1992 39 patients with lymphoma presenting in bone were seen at
      the Royal North Shore Hospital (RNSH), Sydney. Of these, 12 (31%) had truly
      localised disease (Stage IE). AIMS: Patients were studied retrospectively to
      determine the prognostic significance of bony involvement per se versus
      involvement of a single bony site, and to determine the impact of treatment
      modality on outcome. METHODS: The 39 patients were divided into three groups
      according to extent of disease; single osseous site (Stage IE), multifocal bone,
      and bone plus visceral and/or nodal disease. Kaplan-Meier survival curves were
      constructed, and five year actuarial survival stated. Cox regression analysis was
      used to determine hazard ratios. Overall survival was used as the end-point.
      RESULTS: A trend for better survival was noted with Stage IE disease. Multifocal
      and disseminated disease appeared to have a poorer outcome when assessed by
      hazard ratio, with a value of 3 (95% CI 0.87-10.4; p = 0.08), compared to
      unifocal disease. Radiotherapy alone was as effective as combined modality
      treatment although patient numbers were too small for statistical confirmation.
      CONCLUSIONS: The stage of lymphoma, rather than bony involvement per se, seems to
      have more prognostic importance. Radiotherapy alone offered equivalent results to
      combined modality treatment in this series.

PMID- 7717924
TI  - Epidemiology of hypothermia: fatalities and hospitalisations in New Zealand.
AB  - BACKGROUND: Hypothermia occurs within domestic and non-residential settings. Most
      epidemiological data originate from the northern hemisphere, with little data
      being generally available concerning cases from New Zealand and Australia. AIMS:
      The National Health Statistics Centre (New Zealand) records hospital discharges
      and deaths. This study isolated hypothermia cases, to quantify its incidence and
      identify risk groups. METHODS: The morbidity and mortality files for the years
      1979-86 (cases = 3,808,717) and 1977-86 (cases = 259,325; respectively) were
      searched by three investigators. RESULTS: Hypothermia hospitalisations were
      identified (6.9 per 100,000 per year). There were 176 deaths from hypothermia,
      representing 0.07% of the 259,325 deaths from all causes for the same period
      (0.537 per 100,000 people per year); of these fatalities, 72.2% were classified
      as domestic, and 27.8% as non-residential; of the domestic fatalities, 86.6% were
      65 + years and 35.5% of these were male. Within the non-residential category,
      75.5% were aged 13-65, of which 94.6% were male. The hospitalisation incidence
      was 12.7 times the fatality incidence, with the majority of hospitalisations
      being of domestic origin (88.4% of total), and occurring mostly within the lower
      and upper age extremes. Neonatal domestic hypothermia accounted for 72.6% of all
      domestic hospitalisations, and the elderly constituted 72.0% of the remaining
      cases. The proportion of New Zealand fatalities caused by hypothermia was 0.067%;
      lower than reported in the United Kingdom. CONCLUSIONS: The two main non-neonatal
      groups contributing to cases of hypothermia were males aged 13-65 years, and the
      elderly. In the aged, the proportion of hypothermia-related deaths was no
      different from that associated with other disorders, however, the case-fatality
      ratio was three times greater, highlighting the need for improving prevention and
      management strategies.

PMID- 7717925
TI  - Genetic haemochromatosis--preventable rust.

PMID- 7717926
TI  - After the meta-analyses: a commentary on treatment of dyslipidaemia in the
      primary prevention of coronary heart disease.

PMID- 7717927
TI  - Kaposi's sarcoma post renal transplantation.

PMID- 7717928
TI  - Fractures of the tibial plateau in the elderly as a cause of immobility.

PMID- 7717929
TI  - Transfusion management of a patient with IGA deficiency and anti-IGA during liver
      transplantation.

PMID- 7717930
TI  - Hypopituitarism in a diabetic: a reminder of the Houssay phenomenon.

PMID- 7717931
TI  - Once daily dosing of aminoglycosides.

PMID- 7717933
TI  - Air embolism--a neglected cause of stroke complicating cardiopulmonary bypass
      (CPB) surgery.

PMID- 7717932
TI  - Once daily dosing of aminoglycosides.

PMID- 7717934
TI  - Treatment of exogenous lipoid pneumonia by whole lung lavage.

PMID- 7717935
TI  - Microscopic pulmonary tumour embolism: an unusual presentation of malignancy.

PMID- 7717936
TI  - Thyrotropinomas in multiple endocrine neoplasia type 1 (MEN-1).

PMID- 7717937
TI  - The role of surgery in locally advanced breast cancer.

PMID- 7717938
TI  - Informed consent in Australia.
AB  - Recent decisions in Australian courts affirm three important principles relating
      to consent to therapy. First, patients must be appropriately and adequately
      informed. Second, the scope and detail of the information supplied should be
      based on the reasonable patient's need to know rather than on the actions of the
      reasonable doctor. Third, the doctor must take care to ensure that the
      information imparted is understood by the patient. This publication reviews the
      basis of informed consent and traditional beneficent-style consent. The occasions
      when beneficence is more appropriate are outlined.

PMID- 7717940
TI  - Frantz's tumour: papillary and cystic carcinoma of the pancreas.
AB  - Frantz's tumour (papillary and cystic tumour) of the pancreas is a rare neoplasm
      usually seen in young women. It is of low grade malignancy and deserves special
      note among pancreatic malignancies as it is frequently amenable to local
      resection and has a good long-term survival rate after excision. Three such cases
      have been treated at Westmead Hospital, one young male and two females. In two
      the disease was confined to the pancreas. In one, local invasion outside the
      pancreas and trans-coelomic spread to the ovaries was present at the time of
      diagnosis. Complete surgical removal of macroscopic disease was achieved in all
      three and all remain disease free between 2 and 4 years post-surgery. All have
      good exocrine and endocrine pancreatic function. These cases are discussed in
      detail. The need to be aware of this uncommon variant of pancreatic cancer is
      stressed. Investigation and treatment options are reviewed. The role of cytology
      studies in diagnosis and the potential for long-term surgical control of this
      tumour are highlighted on the basis of our limited experience and that presented
      in recent surgical literature.

PMID- 7717939
TI  - Locally advanced breast cancer: is surgery warranted following chemotherapy?
AB  - Various methods of management of locally advanced breast cancer have been
      proposed, including combinations of chemotherapy, surgery, radiotherapy,
      immunotherapy and hormone manipulation. This retrospective study evaluated the
      effectiveness of chemotherapy in the management of locally advanced breast cancer
      in pre- and perimenopausal women by examining the pathology of the mastectomy
      specimens. Sixteen women who on initial clinical examination had breast cancers
      measuring 5 cm or greater underwent chemotherapy prior to surgery. Four women
      were also treated with radiotherapy prior to surgery. All 16 women underwent
      mastectomy and axillary clearance. All specimens showed residual tumour in the
      mastectomy specimen or the regional lymph nodes. Chemotherapy is useful in
      reducing tumour burden to allow surgical resection, but does not produce
      centripetal shrinkage of tumour, nor sterilize the breast of cancer. In this
      small series, the addition of radiotherapy also failed to clear the patient of
      tumour. Wide surgical excision including the original tumour margins is thus
      required to achieve locoregional control. Until chemotherapy and radiotherapy
      regimens can be proved to sterilize the breast of tumour, we caution against the
      use of any surgery less than total mastectomy if optimal local control is to be
      achieved for locally advanced breast cancer in pre- and perimenopausal women.

PMID- 7717941
TI  - Management of transected pancreas in children.
AB  - The pancreas is the fourth most commonly injured intra-abdominal organ in
      children who sustain blunt abdominal trauma. Appropriate management of the
      injured pancreas has been controversial. With the advent of the computerized
      tomography scan, paediatric surgeons have tended to manage pancreatic injuries
      non-operatively. However, if pseudocysts develop, non-operative management may
      necessarily entail a long hospital course involving total parenteral nutrition,
      drainage procedures and attendant morbidity. The critical element in planning
      therapy is to determine the status of the pancreatic duct. We have recently
      encountered five children who suffered blunt pancreatic injury where the main
      pancreatic duct was determined to have been transected. These children underwent
      spleen preserving distal pancreatectomy with resultant shorter hospital stays and
      minimal long-term morbidity. We suggest that in children with pancreatic injury
      where the main pancreatic duct has been transected early operative management
      rather than non-operative therapy is the procedure of choice. Endoscopic
      retrograde cholangiopancreatography should be used to determine the status of the
      pancreatic duct. This modality can be both diagnostic and therapeutic in
      appropriate circumstances.

PMID- 7717942
TI  - The management of splenic rupture in infectious mononucleosis.
AB  - Non-operative management of splenic trauma is now well established; however, the
      role of conservative management in spontaneous splenic rupture is undetermined.
      The leading cause of spontaneous splenic rupture is infectious mononucleosis. We
      report on the management of four patients with spontaneous rupture, in
      association with infectious mononucleosis. Three patients eventually required
      splenectomy, and one was successfully managed non-operatively. The comparative
      risks of operative and non-operative management are discussed. We believe that
      when splenic rupture complicates infectious mononucleosis, early splenectomy is
      the most appropriate management.

PMID- 7717943
TI  - Reconstruction of total loss of upper lip with hair-bearing flaps.
AB  - Carcinoma of the lip is a relatively common problem in Papua New Guinea,
      accounting for some 12% of all malignant tumours in the oral cavity. The cancer
      is associated with chewing betelnut with slaked lime and smoking. Advanced
      squamous cell carcinoma of the upper lip is necessarily managed by primary
      surgery when radiotherapy facilities are not available. Adequate surgical
      treatment of these carcinomas usually requires full thickness excision of a
      portion or whole of the lip. The purpose of this paper is to demonstrate the role
      of hair-bearing scalp flap for reconstruction of total loss of the upper lip in
      male patients.

PMID- 7717944
TI  - Single stage excision of preauricular sinus.
AB  - A total of 44 patients with preauricular sinus underwent one-stage surgical
      treatment. There were 32 unilateral and 12 bilateral cases giving a total of 56
      sinuses. Of these 16 were infected at the time of presentation. Based on the
      observation that preauricular sinus represents the duct of a preauricular gland
      which is closely adherent to the fibrocartilage of the ear, the authors propose a
      method for the complete cure of this lesion by excising the whole gland and duct
      together. This technique was used in all cases including 16 patients with
      infected sinuses. There were three recurrences, two of which were due to
      incomplete excision of the gland. The third case was found to have a fistula
      leading to an atretic external auditory canal. All other patients have shown no
      evidence of recurrence on follow up of six months or longer. Our experience has
      shown that preauricular sinus can be effectively treated at any stage by a simple
      surgical technique based on a clear understanding of the underlying anatomy of
      the lesion.

PMID- 7717945
TI  - Injuries to the ulnar carpometacarpal region: are they being underdiagnosed?
AB  - Thirteen cases with radiographic evidence of injury to the ulnar side of the hand
      are reviewed. These injuries included intraarticular fractures and/or
      dislocations of the fourth and fifth carpometacarpal joints and associated bones
      collectively discussed here as the ulnar carpometacarpal region. In nine the
      extent of the injury was not appreciated on first presentation. Injuries to this
      region are often difficult to assess clinically and radiographically even in
      experienced hands. In our experience computerized tomography (CT) scans in the
      longitudinal and longitudinal oblique axis best display the ulnar carpometacarpal
      joint surfaces and their relationship to each other. We recommend CT of the ulnar
      carpometacarpal region where clinical evidence of an injury to this region is not
      in keeping with the plain radiographic findings, and when planning surgery on a
      complex injury in this region.

PMID- 7717947
TI  - Issues in biomedical statistics: comparing means under normal distribution
      theory.
AB  - The test used most commonly in biomedical research to compare means when
      measurements have been made on a continuous scale is Student's t-test, followed
      closely by various forms of analysis of variance. These tests require that
      defined populations have been randomly sampled, but there are other assumptions
      about populations and samples that must be satisfied. These include: (i)
      normality of the population distributions; (ii) equal variance in those normal
      populations; and (iii) statistical independence of the samples. This review
      offers advice to investigators on how to recognize breaches of the assumptions of
      normality and equality of variance, and how to deal with them by modifying the
      usual t-test or by transforming the experimental data. The sample-size also has
      an important bearing on statistical inferences: (i) if it is too small, the risk
      of Type II error is inflated; and (ii) inequality of sample size exaggerates the
      effects of inequality of variance. The assumption of independence is breached if
      repeated measurements are made serially rather than in random order, but
      adjustments to analysis of variance can be made to correct for the inflated risk
      of Type I error. The review also considers the problem of making multiple
      comparisons of means, and recommends solutions.

PMID- 7717946
TI  - Distal clavicular excision: a detailed functional assessment.
AB  - Distal clavicular excision is commonly performed for a number of clinical
      conditions. The results of the procedure are not well described. Using the
      Constant, American Shoulder and Elbow Surgeons (ASES), University of California
      at Los Angeles (UCLA) and Neer scoring systems, the medium term results of distal
      clavicular excision were assessed. Over an 8 year period, 39 patients underwent
      distal clavicular excision for conditions other than acromioclavicular
      instability (subluxation or dislocation). A single technique was employed. A
      retrospective study was performed of all 18 patients who could be contacted. In
      those cases patient satisfaction was universal. Pre-operative pain was severe in
      16 patients (89%) and moderate in two (11%). Following surgery, five (28%) were
      free from pain, 10 (55%) had only mild or occasional pain, and three (17%)
      reported moderate pain. The difference between pre-operative and postoperative
      levels of pain was highly significant (P < 0.001). However, continuing
      difficulties with work (59%), sleeping (55%) and activities of daily living (59%)
      were reported. Ten of 14 (71%) wishing to return to sporting activities were able
      to do so without restriction. Neither shoulder strength nor range of movement was
      fully restored following surgery, which relieved pain but did not restore
      normality. This series may facilitate subsequent assessment of arthroscopic
      distal clavicular excision.

PMID- 7717948
TI  - Report of a workshop to review urological training in Australasia.
AB  - A review of the current Australasian urological training programme was undertaken
      by members of the Urological Society of Australasia in a workshop format. The
      participants worked in small groups developing strategies to overcome problems
      which the whole group had identified previously. The strategies proposed by the
      groups were subsequently edited and definitive recommendations developed. This
      paper details the final recommendations of the workshop and the intended steps
      towards their implementation.

PMID- 7717949
TI  - Urological training in Australasia: perceptions of recent fellows and current
      trainees.
AB  - In this study we sought to determine the opinions of recent Fellows and current
      trainees on the state of urological training in Australasia. Self administered
      questionnaires were mailed to all urologists in Australia and New Zealand who had
      obtained their FRACS from 1988 to the present, as well as all current advanced
      urological trainees. Eight-seven per cent of Fellows and ninety-four per cent of
      trainees completed and returned the questionnaire. Most Fellows and trainees felt
      that their training adequately equipped them for subsequent independent practice.
      At the completion of training and FRACS examination the majority of respondents
      felt competent in dealing with most urological conditions. However, many did not
      feel confident with paediatric and specialized or complex adult urology,
      particularly oncology and reconstruction. Post-Fellowship training, however,
      appears valuable in overcoming these deficiencies. Several limitations were also
      noted as a consequence of the fact that training is based entirely in the public
      hospital system. This created particular difficulties with respect to outpatient
      or 'office' urology as well as exposure to some non-acute conditions such as
      urinary incontinence and infertility. The current research requirements of
      training do not appear to provide trainees with an adequate knowledge of
      scientific method, with many respondents not feeling equipped to critically
      appraise urological literature. High levels of competence are also not attained
      for other important professional skills, particularly communication with other
      medical practitioners. Despite its importance for learning, feedback on progress
      is not adequately provided and this was seen as a major problem with current
      urological training in Australasia. The majority of respondents felt that mentors
      required specific training to facilitate feedback to trainees.

PMID- 7717950
TI  - Management of perforation of the duodenum following endoscopic sphincterotomy: a
      proposal for selective therapy.

PMID- 7717951
TI  - Choledochoplasty for cholecystocholedochal fistula (Mirizzi syndrome type II): a
      case report and literature review.
AB  - The following is a case report of a cholecystocholedochal fistula (Mirizzi
      syndrome Type II) in a 61 year old woman. The use of a pedicled graft of gall
      bladder remnant in the treatment of this condition is presented. If the condition
      is recognized early, bile duct injury can be prevented and the need for more
      complex techniques of bile duct repair or bypass may be averted.

PMID- 7717952
TI  - Small bowel obstruction secondary to administration of activated charcoal.

PMID- 7717953
TI  - Acute sciatic neuropathy complicating living donor renal transplantation.

PMID- 7717954
TI  - Giant double parathyroid adenoma presenting as a hypercalcaemic crisis.
AB  - The largest documented case of a double parathyroid adenoma is reported. The
      patient presented in hypercalcaemic crisis with a large intrathoracic mass. After
      removal of a massive cystic parathyroid adenoma from the right superior
      mediastinum, a second very large parathyroid adenoma was found on the
      contralateral side adjacent to the left thyroid lobe. This case illustrates the
      importance of the cervical approach, as well as routine bilateral neck
      exploration, for all cases of primary hyperparathyroidism.

PMID- 7717955
TI  - Struvite renal calculi caused by Corynebacterium group D2.

PMID- 7717956
TI  - [Teat amputation in cattle--indications, surgical results and economy].
AB  - Based on the experience gained after the performance of 204 teat amputations with
      complete closure of the wound, medical as well as economic aspects were
      discussed. Various types of severe teat injuries leading to a teat amputation
      were listed. Surgery was successful in 94.6% of all animals subjected to the teat
      amputation. Approximately 50% of the animals had a reproductive life span after
      surgery of more than one year. The most common reasons for culling were
      inconvenience at milking and insufficient milk yield. The milk yield during a
      lactation period dropped by an average of 5.5%. Cost efficiency of the procedure
      was evaluated by partial budgeting. The result of this analysis suggested that in
      most cases, from the economic standpoint of view, there might be an indication
      for teat amputation.

PMID- 7717957
TI  - [Bovine progressive degenerative myeloencephalopathy ("Weaver syndrome") in brown
      Swiss x Braunvieh cattle: reproductive occurrences, results of embryo transfer].
AB  - In the time between 1989 and 1991 seven Brown Swiss heifers, which had clinical
      signs of the Weaver syndrome were kept at the Bavarian Institute of Animal
      Breeding in Grub. This was in order to investigate this hereditary trait further.
      The number of animals carrying this genetic defect was increased by means of
      embryo transfer. Both cycle observations and ovary controls by means of rectal
      palpation resulted largely in physiological data and findings. All seven animals
      responded to superovulation treatment which was induced by sequential doses of p
      FSH (32 mg) or of a single dose of 2,000 IU PMSG. The donors were flushed a total
      of 32 times without problem. On average 5.3 ova were recovered, 2.8 of which were
      viable and suitable for transfer. These are statistically only 50% of the normal
      value in a routine ET programme. Following the transfer of fresh and frozen
      embryos the pregnancy rate was 53%. There was only one abortion observed from 48
      pregnancies.

PMID- 7717958
TI  - [The peripartal disease complex of the mother sow in the industrial swine
      facility. 3. Slaughter findings of old sows with anamnesis of peripartal
      diseases].
AB  - In an industrial pig production unit ten sows were selected at random. All the
      sows had a puerperal disease in their anamnesis. The sows were slaughtered after
      weaning and subjected to pathological examination. The mammary glands, uteri and
      bladder of ten slaughtered sows were examined for gross pathological alterations.
      All the sows showed symptoms of chronic mastitis (abscess, granuloma, fibrosis or
      cysts). Four of the examined uteri showed pathological alterations. Nine out of
      the ten bladders examined revealed pathological findings.

PMID- 7717959
TI  - [The quantitative passage of immunoglobulins from the intestine into the blood
      vessels in newborn lambs].
AB  - A trial with 69 lambs examined the effect of the feeding regime on the transfer
      of colostral immunoglobulins from the intestinal lumen to the circulating blood.
      The lambs received 125 ml of bovine colostral milk per kg birth weight at each
      feeding in the first 24 hours after birth. There were four experimental groups.
      Feeding intervals were either 2 or 6 hours and the milk was administered with or
      without doubling the fluid volume by addition of tap water. Serum concentrations
      of IgG1, IgG2, IgM and IgA were measured during the experimental period and the
      transport efficiency index for each isotype was calculated. The transport
      efficiency index represents the relationship between the amount of immunoglobulin
      administered in colostral milk and the concentration measured in the blood.
      Feeding in 2 hour intervals produced maximum immunoglobulin concentrations at 30
      hours, while 6 hour feeding intervals achieved the same maximal levels at 24
      hours. The relative proportions of the four immunoglobulin isotypes measured in
      the blood were unaffected by the feeding interval. Doubling the fluid volume
      administered while holding the absolute amount of colostral milk constant,
      resulted in a disproportionate increase in blood IgG1 concentration as compared
      to the other isotypes. Concentrations for IgG2, IgM and IgA remained essentially
      the same as those achieved with undiluted colostral milk. The feeding regimes
      tested did not affect endogenous immunoglobulin synthesis, growth rate or the
      health of the lambs.

PMID- 7717960
TI  - [Spread of a Microsporum canis infection in an agricultural facility (case
      description)].
AB  - In a combined pig production and fattening unit the weaned piglets on the
      flatdecks and some young fattening pigs were suffering from a Microsporum canis
      infection. Besides the pigs the children of the farmer showed skin alterations.
      The infection was spread probably by the cats, which had access to the houses for
      sows and for sows with piglets. In cases of uncertain skin alterations, a
      mycologic etiology should be considered.

PMID- 7717961
TI  - [Effectiveness of Rhodovet for the prevention of coli enterotoxemia in a swine
      breeding facility].
AB  - The coli enterotoxemia caused by Coli serotype 0139 occurred in contrary to the
      generally observed course of this infection through several weeks and was
      exceedingly detrimental. Almost exclusively the shock and oedema form of coli
      enterotoxemia was seen. The application of usual schemes of prophylaxis and
      therapy did not effect durable reduction of animal losses. With the daily oral
      application of Rhodovet, a drug containing thiocyanate, in doses of 3.5 kg/t feed
      during 5 weeks the morbidity resp. mortality could be decisively reduced.

PMID- 7717962
TI  - [The effect of thioglycoside-containing feed on the growth, thyroid hormone and
      thiocyanate status of swine and poultry].
AB  - Feed containing rapeseed meal (RSM) with high glucosinolate content (10 mmol/kg
      feed) induced a strong increase of thyroid weight in pigs and poultry.
      Supplementary iodine reduced the antithyroid effect, but, it could not cancel it.
      Only at a low glucosinolate content (0.7 mmol/kg feed) a normal weight of thyroid
      was established. As the iodine supplementation increased the serum T4 value
      increased. The thiocyanate serum level increased irrespective of glucosinolate
      content of the feed. The urine level was significantly decreased due to lower
      dietary glucosinolate level. Obviously, the goitrogenic effect of the RSM does
      not correlate with the increased thiocyanate serum level.

PMID- 7717963
TI  - Acetylation of p-aminobenzoylglutamate, a folic acid catabolite, by recombinant
      human arylamine N-acetyltransferase and U937 cells.
AB  - N-acetyl-p-aminobenzoylglutamate is a major urinary metabolite of folic acid. It
      is formed by acetylation of p-aminobenzoylglutamate following cleavage of the C9
      N10 bond of folic acid. Using recombinant human type 1 (NAT1) and type 2 (NAT2)
      arylamine N-acetyltransferase, we have shown that p-aminobenzoylglutamate is a
      specific NAT1 substrate. At an acetyl-CoA concentration of 50 microM, the Km for
      p-aminobenzoylglutamate (pABG) acetylation by recombinant NAT1 was 130 +/- 13
      microM. For the human pro-monocytic cell-line U937, the apparent Km was slightly
      higher (333 +/- 17 microM). Inhibitor studies supported NAT1-dependent
      acetylation of pABG by U937 cell cytosols. These studies are the first to
      identify a potential endogenous substrate for human NAT1 and suggest that this
      enzyme may be important in the cellular clearance of pABG.

PMID- 7717964
TI  - Temperature-induced alteration of inositolphosphorylceramides in the putative
      glycosylated lipid precursors of Tetrahymena mimbres glycosylphosphatidylinositol
      anchored proteins.
AB  - Tetrahymena species contain relatively prominent glycosylphosphatidylinositol
      (GPI)-anchored proteins as well as their putative precursor phosphatidylinositol
      (PI) glycans. We have characterized the lipid components of the two principal T.
      mimbres PI glycans. Following their purification by preparative TLC, the PI
      glycans were hydrolysed in methanolic HCl or NaOH, and resulting lipids were
      analysed by chromatography and mass spectrometry. The two PI glycans contained
      nearly identical lipid moieties having long-chain bases with N-linked fatty
      acids. The predominant long-chain base, 3-O-methylsphinganine, was first assumed
      to be O-methylated as an artifact of hydrolysis, but subsequently, on the basis
      of control experiments, it was shown to be naturally occurring. PI glycans from
      cells grown at 28 degrees C contained primarily palmitic acid (79%) and some
      stearic acid (11%), whereas the principal PI glycan from 38 degrees C-grown T.
      mimbres contained 65% stearic acid. In 15 degrees C-grown cells stearic acid
      accounted for only 2% of ceramide-bound fatty acids and was almost totally
      replaced by palmitic acid (95%). The distributions of fatty acids bound to T.
      mimbres GPI-anchored proteins [Ko, Hung and Thompson (1995) Biochem. J. 307, 115
      121] were similar but not identical to those of the PI glycans described here.
      Temperature-induced specification of the lipid components of mature T. mimbres
      GPI-anchored proteins appears to be established both at the level of PI-glycan
      synthesis and the level of PI-glycan utilization for protein attachment.

PMID- 7717965
TI  - Temperature regulation of the Tetrahymena mimbres glycosylphosphatidylinositol
      anchored protein lipid composition.
AB  - By incubating Tetrahymena mimbres cells with [3H]myristic acid, [3H]ethanolamine,
      [3H]inositol, and [3H]mannose, proteins having apparent molecular masses of 23
      and 63 kDa were identified as the cells' principal glycosylphosphatidylinositol
      (GPI)-anchored proteins. These proteins accounted for as much as 2-5% of the
      whole cell proteins, with the higher levels being recovered from non-growing
      cells. The two proteins, gpi 23 and gpi 63, were purified to near homogeneity
      through Triton X-114/water partitioning followed by preparative SDS/PAGE. The
      lipid components of the GPI anchors were determined by chemical and enzymic
      hydrolysis. Both proteins were anchored by ceramides, with the principal long
      chain base being C18 sphinganine containing an O-methyl group at the 3 position.
      O-Methylation was shown not to be an artifact of hydrolysis. When T. mimbres was
      cultured at 15 degrees C, the ceramide fatty acid component of the GPI anchors
      was principally palmitic acid (75% in gpi 23 and 76% in gpi 63). GPI anchors from
      28 degrees C-grown cells contained mainly stearic acid (79% in gpi 23 and 70% in
      gpi 63). Temperature change had little effect on the long-chain-base composition.
      The direction of temperature-induced lipid change in the protein-bound anchors
      was the same as found in the inositolphosphorylceramide putative precursors of
      the protein anchors described in the accompanying paper [Hung, Ko and Thompson
      (1995) Biochem. J. 307, 107-113], but the detailed fatty acid compositions of the
      precursors and the protein-bound lipids were quite different. The precise
      metabolic regulation of anchor lipid chain length supports the concept that
      composition of the lipid anchor is important in the function and/or metabolism of
      the anchored protein.

PMID- 7717966
TI  - Deletions at the C-terminus of interferon gamma reduce RNA binding and activation
      of double-stranded-RNA cleavage by bovine seminal ribonuclease.
AB  - Recombinant interferon gamma (IFN-gamma) from three species activates the
      cleavage of double stranded (ds-) RNA by the dimeric RNAase isolated from bovine
      semen (BS-RNAase). Human and bovine IFN-gamma bind RNA tightly enough to inhibit
      cleavage by RNAase A [Schein, Haugg and Benner (1990) FEBS Lett. 270, 229-232].
      Murine IFN-gamma and a proteolytic fragment of human IFN-gamma, both of which
      lack part of the positively charged C-terminus, bind RNA weakly and do not
      inhibit RNAase A. Their ability to activate BS-RNAase is proportional to their
      activity in the anti-viral assay. Two monoclonal antibodies that neutralize the
      anti-viral activity of human IFN-gamma inhibit the activation of BS-RNAase by
      both full-length and proteolysed human IFN-gamma. Our results demonstrate that
      the C-terminus of IFN-gamma contributes to RNA binding and activation of BS
      RNAase, as well as to anti-viral activity.

PMID- 7717967
TI  - Wild-type and mutant D-xylose isomerase from Actinoplanes missouriensis: metal
      ion dissociation constants, kinetic parameters of deuterated and non-deuterated
      substrates and solvent-isotope effects.
AB  - The metal-ion dissociation constants (Mg2+, Mn2+) of wild-type and mutant D
      xylose isomerases from Actinoplanes missouriensis have been determined by
      titrating the metal-ion-free enzymes with Mg2+ and Mn2+ respectively.
      Substitution of amino acids co-ordinated to metal-ion 1 (E181D, D245N)
      dramatically affects the dissociation constants, pH-activity profiles and
      apparent substrate binding. Mutagenesis of groups ligated to metal-ion 2 is less
      drastic except for that of Asp-255: a decrease in metal-ion affinity, a change in
      metal-ion preference and an improved apparent substrate binding (at pH values
      above the optimum), especially in the presence of Mn2+, are observed for the
      D255N enzyme. Similar effects, except for a slightly increased metal-ion
      affinity, are obtained by mutagenesis of the adjacent Glu-186 to Gln and the
      unconserved Ala-25 to Lys. Moreover, the striking acidic-pH shifts observed for
      the D255N and E186Q enzymes support the crucial role of the water molecule, Wa
      690, Asp-255 and the adjacent Glu-186 in proton transfer from 2-OH to O-1 of the
      open and extended aldose substrate. Mutations of other important groups scarcely
      affect the metal-ion dissociation constants and pH-activity profiles, although
      pronounced effects on the kinetic parameters may be observed.

PMID- 7717968
TI  - Cloning, sequencing and expression of the pyrophosphate-dependent phosphofructo-1
      kinase from Naegleria fowleri.
AB  - The cDNA for the PPi-dependent phosphofructo-1-kinase has been cloned and
      sequenced from a cDNA library prepared from the free-living amoeba Naegleria
      fowleri. The coding sequence of the cDNA consists of 1311 bases which translates
      into 437 amino acids with a molecular mass of 48095 Da. Comparison of the
      sequence with those of the previously described sequences of PPi-dependent
      phosphofructokinases from Propionibacterium freudenreichii and potato tuber
      revealed amino acid identities of 23 and 28% respectively and high conservation
      in those regions assumed to be part of the active site. The reading frame was
      cloned into an expression vector, which was transformed into Escherichia coli.
      Extracts of the transformed cells contained PPi-dependent phosphofructokinase
      activity that could be purified to homogeneity. The activity was lost on
      incubation with the chaotropic agent, KSCN, and recovered by subsequent
      incubation with AMP. These properties are consistent with those described by
      Mertens, De Jonckheere and Van Schaftingen [Biochem. J. (1993) 292, 797-803] for
      the enzyme prepared from Naegleria and support the idea that the cloned cDNA
      coded for the complete native enzyme. No nucleotide-binding motif or evidence for
      a nucleotide-binding site characteristic of the ATP-dependent
      phosphofructokinases could be found within the primary structure.

PMID- 7717969
TI  - Evidence for a general role for non-catalytic thermostabilizing domains in
      xylanases from thermophilic bacteria.
AB  - A genomic library of Clostridium thermocellum DNA constructed in lambda ZAPII was
      screened for xylanase-expressing clones. Cross-hybridization experiments revealed
      a new xylanase gene isolated from the gene library, which was designated xyn Y.
      The encoded enzyme, xylanase Y (XYLY), displayed features characteristic of an
      endo-beta1,4-xylanase: the enzyme rapidly hydrolysed oat spelt, wheat and rye
      arabinoxylans and was active against methyl-umbelliferyl-beta-D-cellobioside, but
      did not hydrolyse any cellulosic substrates. The pH and temperature optima of the
      enzyme were 6.8 and 75 degrees C respectively, and the recombinant XYLY,
      expressed by Escherichia coli had a maximum Mr of 116000. The nucleotide sequence
      of xyn Y contained an open reading frame of 3228 bp encoding a protein of
      predicted Mr 120 105. The encoded enzyme contained a typical N-terminal 26
      residue signal peptide, followed by a 164 amino acid sequence, designated domain
      A, that was not essential for catalytic activity. Downstream of domain A was a
      351-residue xylanase Family F catalytic domain, followed by a 180-residue
      sequence that exhibited 28% sequence identity with a thermostable domain of
      Thermoanaerobacterium saccharolyticum xylanase A. The C-terminal portion of XYLY
      comprised the 23-residue duplicated docking sequence found in all other C.
      thermocellum plant cell wall hydrolases that are constituents of the bacterium's
      multienzyme complex, termed the cellulosome, followed by a 286-residue domain
      which exhibited 32% sequence identity with the N-terminal region of C.
      thermocellum xylanase Z. The enzyme did not contain linker sequences found in
      other C. thermocellum plant cell wall hydrolases. Analysis of truncated forms of
      XYLY and hybrid proteins, comprising segments of XYLY fused to the E. coli
      maltose binding domain, confirmed that XYLY contained a central catalytic domain
      and an adjacent thermostable domain. The C-terminal domain did not bind to
      cellulose or xylan. Western blot analysis using antiserum raised against XYLY
      showed that the xylanase was located in the cellulosome and did not appear to be
      extensively glycosylated. The non-catalytic domains of XYLY are discussed in
      relation to the general stability of thermophilic xylanases.

PMID- 7717970
TI  - Epidermal growth factor-stimulated parathyroid hormone-related protein expression
      involves increased gene transcription and mRNA stability.
AB  - Epidermal growth factor (EGF) produced rapid and striking effects on parathyroid
      hormone-related protein (PTHrP) gene expression in the immortalized human
      keratinocyte cell line, HaCaT. Steady-state levels of PTHrP mRNA and secreted
      PTHrP were increased 10-fold by maximally effective concentrations of EGF. EGF
      increased both PTHrP gene transcription and PTHrP mRNA stability. Nuclear run-on
      assays demonstrated a 4-fold increase in transcriptional rate in EGF-stimulated
      cells while transient transfection analysis indicated that the action of EGF on
      transcription involved both the GC-rich promoter, P2, and the downstream TATA
      promoter, P3, but apparently not the upstream TATA promoter, P1. In experiments
      where EGF treatment produced more stable PTHrP transcripts, the half-life of c
      fos mRNA was unaltered, suggesting a relatively specific effect of EGF. Moreover,
      only those species of PTHrP mRNA containing two of the alternative 3' exons
      (exons VII and VIII) were stable, those containing exon IX were not. Reverse
      transcription PCR demonstrated that EGF produced differential increases in the
      abundance of PTHrP mRNA species initiated by the three PTHrP promoters. The major
      effect was seen on the abundance of transcripts initiated by P1 and P2, with less
      marked regulation of P3-initiated transcripts. Thus EGF regulation of PTHrP gene
      expression in HaCaT cells is multifactorial and the combination of its actions at
      the 5' and 3' ends of the gene favours the accumulation of subpopulations of
      PTHrP mRNA containing exons I, VII and VIII.

PMID- 7717971
TI  - Activation of alpha-2-adrenoceptors results in an increase in F-actin formation
      in HIT-T15 pancreatic B-cells.
AB  - 1. Alpha-2-adrenoceptor agonists, such as noradrenaline, are potent inhibitors of
      insulin secretion, and it has been suggested that they control a late step in the
      pathway of exocytosis. We have investigated whether this could be related to a
      change in the extent of actin polymerization in the pancreatic B-cell, since
      actin microfilaments are implicated in regulating the access of secretory
      granules to the plasma membrane prior to exocytosis. 2. Cultured HIT-T15
      pancreatic B-cells responded to noradrenaline with an increase in F-actin
      content, as judged by a rise in the fluorescence output after probing of the
      cells with phalloidin (a toxin which binds specifically to F-actin) conjugated to
      rhodamine. The response to noradrenaline was rapid, dose-dependent and sustained
      and could be reproduced by the highly selective alpha-2-agonist UK14,304.
      Examination of HIT-T15 cells by fluorescence microscopy after treatment with
      rhodamine-phalloidin, revealed a significant localization of F-actin immediately
      adjacent to the plasma membrane. The pattern of F-actin distribution in the cells
      was not altered dramatically by noradrenaline, although the intensity of staining
      close to the plasma membrane appeared to be slightly reduced. 3. The increase in
      F-actin content induced by noradrenaline and UK14,304 was inhibited significantly
      by the alpha-2-antagonist idazoxan but not by the alpha-1-selective antagonist
      prazosin. Pretreatment of HIT-T15 cells with pertussis toxin did not lead to any
      direct alteration in F-actin content, although the toxin significantly modified
      the responses induced by noradrenaline and UK14,304. In each case, cells
      incubated for 24 h with pertussis toxin responded to the alpha-2-agonist with an
      enhanced fluorescence output, indicating that F-actin levels had increased still
      further. This did not correlate with any gross change in the distribution of F
      actin as judged by fluorescence microscopy. 4. The results demonstrate that alpha
      2-adrenoceptors are coupled to control of actin polymerization in HIT-T15 cells.
      They suggest that regulation of F-actin formation could be a component of the
      mechanism by which alpha-2-agonists mediate inhibition of insulin secretion.

PMID- 7717972
TI  - The apolipoprotein B3304-3317 peptide as an inhibitor of the lipoprotein
      (a):apolipoprotein B-containing lipoprotein interaction.
AB  - Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease. It is
      characterized by apolipoprotein (a) [apo(a)] disulphide linked to apolipoprotein
      B (apoB), by Cys4057 of apo(a) and possibly Cys3734 of apoB. We call this the
      covalent apo(a):apoB-Lp interaction, to distinguish it from the non-covalent
      Lp(a):apoB-Lp interaction, mediated by the proline-binding kringle-4-like
      domain(s) of Lp(a). The Lp(a):apoB-Lp interaction was inhibited by an apoB
      peptide spanning residues 3304-3317. This peptide was found by a computerized
      search for sites on apoB similar to the plasminogen's kringle-4-binding site of
      alpha 2-antiplasmin. It probably constitutes part of the Lp(a)-binding site on
      apoB because: (1) it corresponds to the alpha 2-antiplasmin minimum binding
      domain for plasminogen's kringle-4; (2) the competitive nature of inhibition [KI
      = (1.5 +/- 0.7) x 10(-4) M, n = 5] suggested that it and apoB-Lp bound to Lp(a)
      by the same mechanism at the same site; and (3) it specifically bound Lp(a) and
      not apoB-Lp, and the bound Lp(a) was dissociated by inhibitors of the Lp(a):apoB
      Lp interaction, 6-aminohexanoic acid and L-proline. Inhibition was independent of
      its proline residue, suggesting that proline in the context of a peptide is not a
      ligand for the kringle(s) which mediated the binding of Lp(a) to apoB-Lp.

PMID- 7717973
TI  - Solvent isotope effect on bile formation in the rat.
AB  - 2H2O affects many membrane transport processes by solvent and kinetic isotope
      effects. Since bile formation is a process of osmotic filtration where such
      effects could be important, we investigated the effects of 2H2O on bile formation
      in the in situ perfused rat liver. Dose finding experiments showed that at high
      concentrations, 2H2O increased vascular resistance and induced cholestasis; at
      60% 2H2O however, a clear dissociation between the vascular and biliary effects
      was observed. Therefore, further experiments were carried out at this
      concentration. The main finding was a reduction in bile salt-independent bile
      flow from 0.99 +/- 0.04 to 0.66 +/- 0.04 microliters.min-1.g-1 (P < 0.001). This
      was associated with a 40% reduction in biliary bicarbonate concentration (P <
      0.001). Choleretic response to neither taurocholate nor ursodeoxycholate was
      altered by 2H2O; in particular, there was a similar stimulation of bicarbonate
      secretion by ursodeoxycholate in the presence of 60% 2H2O. To further elucidate
      this phenomenon, the effect of 2H2O on three proteins potentially involved in
      biliary bicarbonate secretion was studied in vitro. 2H2O slightly inhibited
      cytosolic carboanhydrase and leukocyte Na+/H(+)-exchange, these effects reached
      statistical significance at 100% 2H2O only, however. In contrast, Cl-/HCO(3-)
      exchange in canalicular membrane vesicles was already inhibited by 50% (P <
      0.001) at 60% 2H2O. Finally, there was a slight reduction in biliary glutathione
      secretion while that of the disulphide was not affected. Our results are
      compatible with an inhibition of canalicular Cl-/HCO(3-)-exchange by 2H2O.
      Whether this is due to altered hydration of the exchanger and/or of the
      transported bicarbonate remains to be determined.

PMID- 7717975
TI  - A modular xylanase containing a novel non-catalytic xylan-specific binding
      domain.
AB  - Xylanase D (XYLD) from Cellulomonas fimi contains a C-terminal cellulose-binding
      domain (CBD) and an internal domain that exhibits 65% sequence identity with the
      C-terminal CBD. Full-length XYLD binds to both cellulose and xylan. Deletion of
      the C-terminal CBD from XYLD abolishes the capacity of the enzyme to bind to
      cellulose, although the truncated xylanase retains its xylan-binding properties.
      A derivative of XYLD lacking both the C-terminal CBD and the internal CBD
      homologue did not bind to either cellulose or xylan. A fusion protein consisting
      of the XYLD internal CBD homologue linked to the C-terminus of glutathione S
      transferase (GST) bound to xylan, but not to cellulose, while GST bound to
      neither of the polysaccharides. The Km and specific activity of full-length XYLD
      and truncated derivatives of the enzyme lacking the C-terminal CBD (XYLDcbd), and
      both the CBD and the internal CBD homologue (XYLDcd), were determined with
      soluble and insoluble xylan as the substrates. The data showed that the specific
      activities of the three enzymes were similar for both substrates, as were the Km
      values for soluble substrate. However, the Km values of XYLD and XYLDcbd for
      insoluble xylan were significantly lower than the Km of XYLDcd. Overall, these
      data indicate that the internal CBD homologue in XYLD constitutes a discrete
      xylan-binding domain which influences the affinity of the enzyme for insoluble
      xylan but does not directly affect the catalytic activity of the xylanase. The
      rationale for the evolution of this domain is discussed.

PMID- 7717974
TI  - Regulation of J6 gene expression by transcription factor GATA-4.
AB  - Retinoic acid-induced differentiation of mouse F9 embryonal carcinoma cells into
      primitive endoderm is accompanied by increased transcription of the gene for J6,
      a heat shock protein implicated in collagen biosynthesis. In this paper we
      present evidence that transcription factor GATA-4, a retinoic acid-inducible GATA
      binding protein, is involved in the regulation of J6 gene expression in F9 cells.
      Northern-blot analysis indicates that transcripts encoding GATA-4 and J6 increase
      in parallel during retinoic acid-induced differentiation of F9 cells. Gel-shift
      experiments and antibody binding studies demonstrate that: (1) GATA-4 is the
      major GATA-binding protein activity in differentiated F9 cells, and (2) GATA-4
      binds to consensus GATA motifs in the retinoic acid-responsive portion of the J6
      promoter. Co-transfection studies using NIH 3T3 cells show that GATA-4 is a
      potent trans-activator of the J6 promoter. These lines of evidence suggest that
      expression of J6 in F9 cells is regulated by GATA-4. We speculate that
      transcription factor GATA-4 may also control other genes involved in
      extracellular matrix formation in the yolk sac.

PMID- 7717976
TI  - Interaction of cadmium and oestradiol-17 beta on metallothionein and vitellogenin
      synthesis in rainbow trout (Oncorhynchus mykiss).
AB  - The induction of metallothionein and vitellogenin synthesis in rainbow trout
      liver was studied after injection of oestradiol-17 beta alone or in combination
      with cadmium or zinc. Intraperitoneal injection of oestradiol-17 beta increased
      the liver somatic index, with subsequent induction of vitellogenin synthesis.
      Oestradiol-17 beta did not induce metallothionein synthesis. Injection of cadmium
      induced the synthesis of metallothionein mRNA and metallothionein. Injection of
      oestradiol-17 beta in combination with cadmium resulted in inhibition of
      transcription and translation of both vitellogenin and metallothionein.
      Chromatography of liver cytosols revealed that cadmium, when co-injected with
      oestradiol-17 beta, did not bind to metallothionein but would initially bind to
      high-molecular-mass (HMr) cytosolic proteins. In fish injected with cadmium in
      combination with oestradiol-17 beta, cadmium was gradually redistributed from HMr
      proteins to metallothionein. This resulted in induction of metallothionein
      synthesis and in binding of most of the cadmium to metallothionein. Induction of
      vitellogenin mRNA was observed 15 days after injection, as cadmium was being
      redistributed to newly synthesized metallothionein. These findings indicate that
      cadmium inhibits the transcription of vitellogenin. The binding of cadmium to
      these non-metallothionein proteins represses the induction of metallothionein and
      results in increased toxicity of the metal. Preinduction of metallothionein by
      zinc injections resulted in decreased cadmium sensitivity of the fish and a
      decrease in the repression of vitellogenin mRNA. Furthermore, a role for
      metallothionein in the detoxification of cadmium is indicated by the induction of
      vitellogenin synthesis that occurs once metallothionein has begun sequestering
      cadmium.

PMID- 7717977
TI  - Structure of heparin fragments with high affinity for lipoprotein lipase and
      inhibition of lipoprotein lipase binding to alpha 2-macroglobulin-receptor/low
      density-lipoprotein-receptor-related protein by heparin fragments.
AB  - Heparin-derived deca- and octa-saccharides were subjected to affinity
      chromatography on lipoprotein lipase-Sepharose and the fractions eluted at high
      salt concentration were analysed by strong-anion-exchange chromatography. Two
      high-affinity decasaccharides were isolated and the structure determined by one-
      and two-dimensional 1H-n.m.r. spectroscopy. The affinities of 3H-labelled low
      molecular-mass heparin and size-fractionated deca-, octa-, and hexa-saccharides
      for lipoprotein lipase immobilized on microtitre plates were determined from
      saturation curves. From competition experiments the affinities of unlabelled
      heparins and pure deca- and hexa-saccharide fragments were determined. The
      binding was size- and charge-dependent, but structural dependency was also
      indicated. Thus substitution of a 2-O-sulphated L-iduronic acid with D-glucuronic
      acid was less important than the sulphation pattern of the D-glucosamine residue
      for affinity for lipoprotein lipase. Heparin inhibits binding of lipoprotein
      lipase to alpha 2-macroglobulin-receptor/low-density-lipoprotein receptor-related
      protein. The effects of size, charge and structure for this inhibition were
      studied. The ability of the heparin fragments to inhibit binding correlated with
      their affinity for lipoprotein lipase. This indicates that the inhibition of the
      binding of lipoprotein lipase to alpha 2-macroglobulin-receptor/low-density
      lipoprotein receptor-related protein by heparin is exclusively mediated by
      binding of heparin to lipoprotein lipase.

PMID- 7717978
TI  - The membrane immunoglobulin receptor utilizes a Shc/Grb2/hSOS complex for
      activation of the mitogen-activated protein kinase cascade in a B-cell line.
AB  - Ligation of membrane immunoglobulin M (mIgM) receptor in the Ramos B-cell line
      induced tyrosine phosphorylation of several intracellular substrates, including
      the adaptor protein. Shc. Phosphorylated Shc could be seen to associate with Grb2
      in a complex which included hSOS. Inasmuch as hSOS is involved in p21ras
      activation, we also demonstrated that mIgM ligation activated a Ras-dependent
      kinase cascade in which sequential activation of Raf-1 and MEK-1 culminates in
      the activation of p42 mitogen-activated protein (MAP) kinase (ERK-2). The tumour
      promoter and protein kinase C agonist, phorbol 12-myristate 13-acetate (PMA),
      also activated Raf-1, MEK-1, and MAP kinase in Ramos cells, but did not induce
      tyrosine phosphorylation of Shc or Shc/Grb2 association. Okadaic acid, another
      tumour promoter and serine/threonine phosphatase inhibitor, activated p42 MAP
      kinase without activating Raf-1 or MEK-1, suggesting the existence of a
      serine/threonine phosphatase which directly regulates MAP kinase activity.

PMID- 7717979
TI  - Proteins binding to the leader of the 6.0 kb mRNA of human insulin-like growth
      factor 2 influence translation.
AB  - The leader of the 6.0 kb human insulin-like growth factor 2 (IGF-2) mRNA, leader
      3, has been reported to partially repress translation. In the regulation of this
      phenomenon, RNA-binding proteins may play a role. Using UV-irradiation
      crosslinking, we found specific binding of four proteins (57, 43, 37 and 36 kDa)
      to this leader. Binding of these proteins to RNA proved to be highly sensitive to
      the potassium chloride concentration in the buffer solution, each protein having
      its own optimum. The 57 kDa protein was indistinguishable by size, binding
      properties and immunoprecipitation from the polypyrimidine tract binding protein
      (PTB), first described as a nuclear protein binding to the polypyrimidine tracts
      (PPTs) in introns. Cross-competition experiments showed that leader 3 has a much
      higher affinity for this 57 kDa protein than the PPT on which PTB was originally
      characterized. By competition with different fragments of leader 3, we were able
      to localize the binding of the 57 kDa protein to a 162 nt RNA fragment (AsnI
      PvuII) in the 3'-part of the leader. When placed before a chloramphenicol
      acetyltransferase (CAT) open reading frame, this RNA fragment stimulated
      translation in reticulocyte lysate 3-fold, while other fragments of leader 3
      repressed translation. The efficient translation directed by the 162 nt AsnI
      PvuII fragment fused to CAT could be repressed by adding free AsnI-PvuII RNA
      fragment, indicating that the high translation efficiency of the AsnI-PvuII-CAT
      synthetic mRNA was due to the binding of protein and not to the structure of the
      RNA itself.

PMID- 7717980
TI  - Comparison of metabolic fluxes of cis-5-enoyl-CoA and saturated acyl-CoA through
      the beta-oxidation pathway.
AB  - The metabolic fluxes of cis-5-enoyl-CoAs through the beta-oxidation cycle were
      studied in solubilized rat liver mitochondrial samples and compared with
      saturated acyl-CoAs of equal chain length. These studies were accomplished using
      either spectrophotometric assay of enzyme activities and/or the analysis of
      metabolites and precursors using a gas chromatographic method after conversion of
      CoA esters into their free acids. Cis-5-enoyl-CoAs were dehydrogenated by acyl
      CoA oxidase or acyl-CoA dehydrogenases at significantly lower rates (10-44%) than
      saturated acyl-CoAs. However, enoyl-CoA hydratase hydrated trans-2-cis-5-enoyl
      CoA at a faster rate (at least 1.5-fold) than trans-2-enoyl-CoA. The combined
      activities of 3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase for 3
      hydroxy-cis-5-enoyl-CoAs derived from cis-5-enoyl-CoAs were less than 40% of the
      activity for the corresponding 3-hydroxyacyl-CoAs prepared from saturated acyl
      CoAs. Rat liver mitochondrial beta-oxidation enzymes were capable of metabolizing
      cis-5-enoyl-CoA via one cycle of beta-oxidation to cis-3-enoyl-CoA with two less
      carbons. However, the overall rates of one cycle of beta-oxidation, as determined
      with stable-isotope-labelled tracer, was only 15-25%, for cis-5-enoyl-CoA, of
      that for saturated acyl-CoA. In the presence of NADPH, the metabolism of cis-5
      enoyl-CoAs was switched to the reduction pathway.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7717981
TI  - 3'-untranslated sequences mediate post-transcriptional regulation of 3-hydroxy-3
      methylglutaryl-CoA reductase mRNA by 25-hydroxycholesterol.
AB  - In an earlier study [Choi, Lundquist and Peffley (1993) Biochem. J. 296, 859
      866], we determined that 25-hydroxycholesterol regulates 3-hydroxy-3
      methylglutaryl-CoA (HMG-CoA) reductase mRNA through a post-transcriptional
      mechanism that requires protein synthesis. To investigate whether 3'-untranslated
      sequences play a role in 25-hydroxycholesterol-mediated post-transcriptional
      control, we ligated approx. 1400 bp of the 3'-untranslated region of HMG-CoA
      reductase cDNA to the coding region of human beta-globin DNA. beta-Globin-3'
      untranslated reductase fusion constructs were then transiently expressed in
      Chinese hamster ovary fibroblasts under conditions known to regulate reductase
      mRNA. There were no differences in beta-globin RNA levels in transfected cells
      incubated with or without lovastatin, a competitive inhibitor of reductase.
      However, in the presence of lovastatin and an oxysterol, 25-hydroxycholesterol,
      beta-globin RNA levels were decreased approx. 2-fold. Inhibition of protein
      synthesis with cycloheximide blocked the effects of 25-hydroxycholesterol on beta
      globin RNA. Moreover, replacing the 3'-untranslated sequences with 1367 bp of the
      simian virus 40 enhancer region eliminated the regulatory effect of 25
      hydroxycholesterol. Because the fusion construct has no sterol regulatory
      elements necessary for transcription, our results indicate that the change in
      beta-globin RNA occurred at a post-transcriptional level. In addition, we have
      shown that the 3'-untranslated region of HMG-CoA reductase cDNA imparted
      oxysterol-mediated post-transcriptional regulation to beta-globin RNA, an effect
      that required protein synthesis.

PMID- 7717982
TI  - Characterization of phospholipid methylation in rat brain myelin.
AB  - Highly purified rat brain myelin was solubilized in Triton X-100 and myelin
      phospholipid N-methyltransferase was characterized. The enzyme activities were
      separated by isoelectric focusing and ion-exchange chromatography. The
      phospholipid methyl-transferase has shown at least four peaks of activity with
      pIapp. values of 4.5, 5.2, 6.2 and 8.4. After affinity purification each of these
      activities revealed a close set of bands of approx. 65 kDa on SDS/PAGE. These
      data together with those from preparative SDS/PAGE separations suggested that rat
      brain myelin contains three acidic and at least one basic phospholipid
      methylating isoenzymes and that the major isoenzyme in each case is approx. 65
      kDa in size. While the predominant product of the reaction catalysed by all
      detected isoforms was monomethylated phosphatidylethanolamine, the least acidic
      isoform (pIapp. 6.2) also formed about 20% phosphatidylcholine, suggesting that
      these isoenzymes may play different roles in vivo.

PMID- 7717984
TI  - Permeation of small molecules into the cavity of ferritin as revealed by proton
      nuclear magnetic resonance relaxation.
AB  - The NMR relaxation technique was used to investigate the permeation of molecules
      into the cavity of ferritin. Spin-lattice relaxation times in the rotating frame
      of various probe molecules were measured for solutions of recombinant horse L
      apoferritin without iron and horse spleen apoferritin with very small amounts of
      ferric ions. The results show that molecules larger than the size of the ferritin
      channels can pass through the channels into the ferritin interior, and that the
      maximum size of molecules for the permeation is smaller than maltotriose.

PMID- 7717983
TI  - Quantification of a matrix metalloproteinase-generated aggrecan G1 fragment using
      monospecific anti-peptide serum.
AB  - Several members of the matrix metalloproteinase family have been reported to
      cleave aggrecan in the interglobular domain between Asn-341 and Phe-342. An
      antiserum was prepared against a peptide conjugate corresponding to the C
      terminal sequence of the matrix metalloproteinase-generated aggrecan G1 fragment
      (Phe335-Val-Asp-Ile-Pro-Glu-Asn341). A quantitative radioimmunoassay, with a
      limit of detection of about 80 pM, was developed using this antiserum. This
      antiserum requires the free carboxyl group of the C-terminal asparagine for
      optimal recognition. If the C-terminal asparagine is excised from the sequence,
      replaced with closely related amino acids, or extended across the matrix
      metalloproteinase cleavage site, there is a 40-10,000-fold loss in detection.
      Using peptides cleaved from the N-terminus, it was determined that the antiserum
      requires the entire Phe-Val-Asp-Ile-Pro-Glu-Asn sequence for optimal recognition.
      The radioimmunoassay detects matrix metalloproteinase-generated G1 fragments with
      similar sensitivity to the Phe-Val-Asp-Ile-Pro-Glu-Asn peptide, but it does not
      recognize intact aggrecan. Immunoreactive aggrecan G1 fragments of molecular mass
      50 kDa are generated by the matrix metalloproteinases stromelysin and gelatinase
      A. In contrast, under identical conditions, the closely related
      metalloproteinases, gelatinase B and collagenase, as well as cathepsin G,
      cathepsin B and human leucocyte elastase, did not generate a G1 fragment
      recognized by the antiserum. The anti-Phe-Val-Asp-Ile-Pro-Glu-Asn serum detects
      stromelysin-generated aggrecan G1 fragments from mouse, guinea pig, rabbit and
      human, indicating that the detection is not species-specific. This antiserum and
      radio-immunoassay should be useful for quantifying and characterizing matrix
      metalloproteinase-generated aggrecan G1 fragments in articular cartilage and
      synovial fluids from humans and various animal models of articular-cartilage
      destruction.

PMID- 7717985
TI  - Expression of wild-type and mutated rabbit osteopontin in Escherichia coli, and
      their effects on adhesion and migration of P388D1 cells.
AB  - Recombinant wild-type rabbit osteopontin (rOP) and the protein with an aspartate
      to-glutamate transposition induced by a point mutation in the rabbit OP cDNA
      within the Gly-Arg-Gly-Asp-Ser (GRGDS) sequence were expressed in Escherichia
      coli and purified to homogeneity. P388D1 cells bound rOP in a saturable manner.
      rOP induced adhesion and haptotaxis of P388D1 cells, whereas mutated rabbit OP
      (rOPmut) did not. Anti-rOP IgG F(ab')2 and synthetic GRGDS peptide inhibited rOP
      mediated adhesion and haptotaxis of P388D1 cells. Fibronectin (FN)-mediated
      adhesion of P388D1 cells was markedly inhibited in the presence of fluid-phase
      rOP. Adhesion of P388D1 cells to rOP was significantly inhibited by anti-[alpha
      subunits of VLA4 (alpha 4) and VLA5 (alpha 5)] monoclonal antibodies (mAbs), but
      not by anti-[alpha-subunit of vitronectin (VN) receptor (alpha V) or Mac-1 (alpha
      M)] mAb. Adhesion of P388D1 cells to FN and VN was significantly inhibited by
      anti-alpha V mAb but not anti-alpha 4, -alpha 5 or -alpha M mAb. Haptotaxis of
      P388D1 cells to rOP was significantly inhibited by anti-alpha V mAb, but not by
      anti-alpha 4, -alpha 5 and alpha M mAbs, whereas that to FN showed no inhibition
      with all three mAbs. Haptotaxis of P388D1 cells to VN was significantly inhibited
      by anti-alpha 5 and -alpha V mAbs but not by anti-alpha 4 and -alpha M mAbs.
      Similar features of inhibition of adhesion and haptotaxis of P388D1 cells to
      human OP were observed by mAbs. rOP had no chemotactic effect on P388D1 cells.
      Significant polymorphonuclear leucocyte migration was observed 3-12 h after
      intradermal injection of rOP into rabbits.

PMID- 7717986
TI  - Expression and characterization of maize ZBP14, a member of a new family of zinc
      binding proteins.
AB  - A maize gene (Mz2-12), with a deduced amino acid sequence similar to that of a
      protein kinase C (PKC) inhibitor from bovine brain, has been expressed in
      Escherichia coli and the protein (ZBP14) purified to homogeneity. The bovine
      protein was originally identified by Walsh's group and named PKC inhibitor-1
      (PKCI-1). The recombinant maize protein (ZBP14) shares characteristics of bovine
      PKCI-1: it has similar secondary structure, is dimeric, and has a similar
      affinity for zinc. However, the maize ZBP14 had very little activity as an
      inhibitor of mammalian brain PKC, thus precluding zinc sequestration as the
      mechanism of inhibition. The biological role for the maize protein in plant
      kinase regulation is therefore unclear. In the presence of both maize ZBP14 and
      14-3-3 protein (which inhibits PKC in the absence of diacylglycerol), the effects
      on PKC appeared to be synergistic.

PMID- 7717987
TI  - Interleukin 1-induced phosphorylation of MAD3, the major inhibitor of nuclear
      factor kappa B of HeLa cells. Interference in signalling by the proteinase
      inhibitors 3,4-dichloroisocoumarin and tosylphenylalanyl chloromethylketone.
AB  - The regulation of the inhibitor of nuclear factor kappa B (I kappa B) by
      interleukin 1 (IL1) was investigated in HeLa cells. Two forms of I kappa B were
      resolved by ion-exchange chromatography. The major form (75%) was identified as
      MAD3 by specific antisera. IL1 generated rapidly (6 min) an electrophoretically
      retarded form of MAD3 that was stable in acid and was converted into the
      unmodified form by phosphatase 2A. It thus corresponded to a phosphorylation of
      the protein on serine or threonine. IL1 also caused the disappearance of MAD3
      from the cells, which was complete 15 min after stimulation and coincided with a
      46% reduction of cellular I kappa B activity. Newly-synthesized MAD3 accumulated
      to pre-stimulation levels between 60 and 90 min after stimulation and this
      coincided with the down-regulation of the phosphorylating activity. The serine
      proteinase inhibitors 3,4-dichloroisocoumarin (DCI) and tosylphenylalanyl
      chloromethylketone (TPCK) prevented phosphorylation and disappearance of MAD3. At
      the same concentrations (10-100 microM), they also increased basal
      phosphorylation of the small heat shock protein (hsp27) and prevented the IL1-
      and phorbol 12-myristate 13-acetate-induced increases of its phosphorylation. The
      inhibitors were thus interfering with protein kinases when blocking degradation
      of MAD3. Recombinant MAD3 phosphorylated in vitro by protein kinase C was not
      electrophoretically retarded, suggesting that MAD3 was phosphorylated by another
      kinase in IL1-stimulated cells. Our results suggest that the IL1-induced
      phosphorylation of MAD3 on serine or threonine leads to its degradation. DCI and
      TPCK blocked phosphorylation mechanisms and it could not be concluded that serine
      proteinases were involved in the breakdown of MAD3.

PMID- 7717988
TI  - Importance of the glutamate residue of KDEL in increasing the cytotoxicity of
      Pseudomonas exotoxin derivatives and for increased binding to the KDEL receptor.
AB  - It was previously shown that amino acids 609-613 (REDLK) at the C-terminus of
      Pseudomonas exotoxin (PE) are necessary for cytotoxicity, presumably by directing
      the toxin to the endoplasmic reticulum (ER) [Chaudhary, Jinno, FitzGerald and
      Pastan (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 308-312]. Using the anti
      [interleukin 2 receptor (IL2R)] immunotoxin anti-Tac(Fv)-PE38 (AT-PE38REDLK), it
      was found that removing the terminal lysine did not alter the activity, but
      replacing REDL with KDEL, the most common ER retention sequence, increased
      activity. To determine which amino acid in KDEL was responsible for the increase
      in activity, we tested eight C-terminal mutants of AT-PE38REDLK. Using IL2R
      bearing MT-1 cells, we found that the glutamate residue of KDEL was required for
      high activity, as the cytotoxicity of AT-PE38 ending in KDEL, RDEL, KEEL or REEL
      was much greater than that of AT-PE38 ending in REDL, KEDL, RDDL or KDDL. Using
      freshly isolated lymphocytic leukaemia cells, AT-PE38 ending in KDEL, REEL or
      RDEL was more than 100-fold more cytotoxic than AT-PE38 ending in KEDL, REDL,
      RDDL or the native sequence REDLK. The RDEL sequence also improved the cytotoxic
      activity of an interleukin 4-PE38 toxin fusion protein. Improved cytotoxic
      activity correlated with improved binding of the C-termini to the KDEL receptor
      on rat Golgi membranes. These data indicate that the glutamate residue of KDEL
      improves the cytotoxicity of PE by increasing binding to a sorting receptor which
      transports the toxin from the transreticular Golgi apparatus to the ER, where it
      is translocated to the cytosol and inhibits protein synthesis.

PMID- 7717989
TI  - Oxidative stress and recovery from oxidative stress are associated with altered
      ubiquitin conjugating and proteolytic activities in bovine lens epithelial cells.
AB  - Roles for ubiquitin (an 8.5 kDa polypeptide) involve its conjugation to proteins
      as a signal to initiate degradation and as a stress protein. We investigated
      ubiquitin conjugation and ubiquitin-dependent proteolytic activities in cultured
      bovine lens epithelial cells (BLECs) upon oxidative challenge. A 44% decrease in
      intracellular glutathione confirmed oxidative stress upon incubation with 1 mM
      H2O2. After 30 min incubation, endogenous high-molecular-mass ubiquitin
      conjugates decreased 73%, and intracellular proteolysis decreased about 50%. In
      the supernatants of the oxidatively treated BLECs, the ability to form high
      molecular-mass ubiquitin conjugates with exogenous 125I-labelled ubiquitin
      decreased 28%, and ATP-dependent degradation of oxidized alpha-crystallin
      decreased 36%. When the H2O2-treated BLECs were allowed to recover for 60 min,
      intracellular proteolysis returned to the level of control cells. There was also
      a subsequent transient enhancement of intracellular proteolysis and a
      simultaneous recovery of endogenous high-molecular-mass ubiquitin conjugates. In
      parallel cell-free experiments, conjugating activity with exogenous 125I-labelled
      ubiquitin and ATP-dependent degradation of oxidized alpha-crystallin increased
      35% and 72% respectively compared with non-oxidatively treated BLECs. ATP
      independent proteolysis showed little response to exposure or removal of H2O2.
      These results indicate that (1) the rate of intracellular proteolysis in BLECs is
      associated with the level of endogenous high-molecular-mass ubiquitin conjugates
      and (2) oxidative stress may inactivate the ubiquitin conjugation activity with
      coordinate depression of proteolytic capability. Enhancement in ubiquitin
      conjugation and proteolytic activities during recovery from oxidative stress may
      be important in removal of damaged proteins and restoration of normal function of
      BLECs. The inactivation of ubiquitin-dependent proteolysis by oxidation may be
      involved in the accumulation of altered proteins and other adverse sequelae in
      the oxidatively challenged aging lens.

PMID- 7717992
TI  - Rat mammary-gland transferrin: nucleotide sequence, phylogenetic analysis and
      glycan structure.
AB  - The complete cDNA for rat mammary-gland transferrin (Tf) has been sequenced and
      also the native protein isolated from milk in order to analyse the structure of
      the main glycan variants present. A lactating-rat mammary-gland cDNA library in
      lambda gt10 was screened with a partial cDNA copy of rat liver Tf and
      subsequently rescreened with 5' fragments of the longest clones. This produced a
      2275 bp insert coding for an open reading frame of 695 amino acid residues. This
      includes a 19-amino acid signal sequence and the mature protein containing 676
      amino acids and one N-glycosylation site in the C-terminal domain at residue 490.
      Phylogenetic analysis was carried out using 14 translated Tf nucleotide
      sequences, and the derived evolutionary tree shows that at least three gene
      duplication events have occurred during Tf evolution, one of which generated the
      N- and C-terminal domains and occurred before separation of arthropods and
      chordates. The two halves of human melanotransferrin are more similar to each
      other than to any other sequence, which contrasts with the pattern shown by the
      remaining sequences. Native rat milk Tf is separated into four bands on native
      PAGE that differ only in their sialic acid content: one biantennary glycan is
      present containing either no sialic acid residues or up to three. The complete
      structures of the two major variants were determined by methylation, m.s. and 400
      MHz 1H-n.m.r. spectroscopy. They contain either one or two neuraminic acid
      residues (alpha 2-->6)-linked to galactose in conventional biantennary N-acetyl
      lactosamine-type glycans. Most contain fucose (alpha 1-->6)-linked to the
      terminal non-reducing N-acetylglucosamine.

PMID- 7717991
TI  - Effects of granulocyte-macrophage colony-stimulating factor and tumour necrosis
      factor-alpha on tyrosine phosphorylation and activation of mitogen-activated
      protein kinases in human neutrophils.
AB  - The present study was undertaken to determine the identities and characteristics
      of proteins with molecular masses between 40 and 44 kDa whose tyrosine
      phosphorylation increases in human neutrophils following stimulation of these
      cells with tumour necrosis factor alpha (TNF-alpha) and granulocyte-macrophage
      colony-stimulating factor (GM-CSF). Immunoblotting results demonstrate that
      addition of GM-CSF to human neutrophils increases the tyrosine phosphorylation of
      two proteins with molecular masses of 42 and 44 kDa. However, the addition of TNF
      alpha to neutrophils induces a time- and dose-dependent increase in tyrosine
      phosphorylation of a 40 kDa protein. Immunoprecipitation using specific mitogen
      activated protein kinase (MAPK) isoform antibodies and an antibody which
      recognizes phosphotyrosine-containing proteins demonstrated that the 42 and 44
      kDa proteins are isoforms of MAPKs. Utilizing an in situ gel kinase activity
      assay, GM-CSF increases the kinase activity of the 42 and 44 kDa proteins.
      Moreover, using immunoprecipitated p42 and p44 MAPK isoforms in this gel assay
      revealed activity associated with the p42 and p44 MAPK isoforms. Using the same
      in situ assay, TNF-alpha induces an increase in kinase activity of a 40-42 kDa
      protein. However, the 40 kDa protein whose phosphorylation on tyrosine residues
      increased in human neutrophils following stimulation with TNF-alpha is not a
      member of the known MAPK family, demonstrating the divergences in pathways
      utilized by GM-CSF and TNF-alpha. This 40 kDa protein may be related to the
      recently identified protein that becomes phosphorylated on tyrosine residues upon
      stimulation of the human epidermal carcinoma cell line KB by interleukin-1. In
      these cells the p40 protein is part of a protein kinase cascade which results in
      the phosphorylation of the small heat shock protein, hsp27.

PMID- 7717994
TI  - Oxidation of intracellular glutathione after exposure of human red blood cells to
      hypochlorous acid.
AB  - Exposure of human red blood cells to low doses of hypochlorous acid (HOCl)
      resulted in the loss of intracellular GSH. Oxidation occurred less than 2 min
      after the addition of HOCl, and required approx. 2.5 mol of HOCl per mol of GSH
      lost. Loss of GSH preceded oxidation of membrane thiols, the formation of
      chloramines and haemoglobin oxidation. The susceptibility of intracellular GSH to
      oxidation by HOCl was two-thirds that of GSH in cell lysates. These results
      indicate that HOCl can penetrate the red cell membrane, which provides little
      barrier protection for cytoplasmic components, and that GSH oxidation by HOCl may
      be a highly selective process. Virtually all of the GSH lost was converted into
      GSSG. If glucose was added to the medium, most of the GSH oxidized by low doses
      of HOCl was rapidly regenerated. At higher doses, recovery was less efficient.
      However, when HOCl was added as a slow infusion rather than in a single bolus,
      there was increased recovery at higher doses. This indicates that in
      metabolically active cells regeneration is rapid and GSH may protect cell
      components from damage by HOCl. HOCl-induced lysis was only slightly delayed by
      adding glucose to the medium, indicating that lytic injury is not ameliorated by
      GSH.

PMID- 7717990
TI  - The binding of natural and fluorescent lysophospholipids to wild-type and mutant
      rat liver fatty acid-binding protein and albumin.
AB  - Rat liver fatty acid-binding protein (FABP) is able to bind a wide range of non
      polar anionic ligands, including lysophospholipids. In order to understand the
      nature of lysophospholipid interactions with liver FABP, the binding of natural
      lysophospholipids and two fluorescent analogues, N-(5
      dimethylaminonaphthalenesulphonyl)-1-palmitoyl-sn-glycero-3- phosphoethanolamine
      (dansyl lysoPE) and 1-(O-[11-(5-dimethylaminonaphthalene-sulphonyl)amino]undecyl)
      sn-glycero -3- phosphocholine (dansyl-C11-lysoPAF), has been investigated. The
      results confirmed the ability of liver FABP to bind lysophospholipids with KD
      values in the range of 1-2 microM, and a 1:1 binding stoichiometry was indicated.
      Binding of fluorescent lysophospholipids was enhanced with the FABP mutant,
      R122Q, possibly due to increased flexibility of the binding cavity as a result of
      reduced hydrogen-bonding constraints. The fluorescent lysophospholipids also
      bound to albumin, with KD values in the range 0.1-1.0 microM, and could be
      displaced by oleic acid. The fluorescence characteristics of the dansyl
      lysophospholipid analogue dansyl-C11-lyso-PAF suggested that this probe binds to
      the same site(s) on albumin as the fluorescent fatty acid probe 11-(5
      dimethylaminonaphthalene-sulphonylamino)-undecanoic acid (DAUDA).

PMID- 7717993
TI  - Cyclophilin-40: evidence for a dimeric complex with hsp90.
AB  - The expression of human cyclophilin 40 (CyP-40) as a glutathione S-transferase
      fusion protein has provided a means to identify cellular components that are in
      association with this ubiquitous protein. When the fusion protein was coupled to
      a GSH affinity matrix, heat-shock protein 90 (hsp90) was found to be the
      predominant associated protein in all tissue extracts examined. The relatively
      high concentration of each of these proteins in various tissues indicates that
      the dimeric complex exists in concentrations that exceed those of the inactive
      steroid receptors of which each protein is a component. Association does not
      occur with heat-shock protein 70 and is not affected by cyclosporin A (CsA).
      Independent expression of two domains of CyP-40 permitted dissociation of N
      terminal isomerase and CsA binding activity from the hsp90 binding site, which is
      located at the FKBP-59-like C-terminal region. The biological association of CyP
      40 with hsp90 in many tissues may reflect a conjoint role in protein folding and
      trafficking.

PMID- 7717996
TI  - Mutations within a highly conserved sequence present in the X region of
      phosphoinositide-specific phospholipase C-delta 1.
AB  - Phosphoinositide-specific phospholipase C (PI-PLC) enzymes have considerable
      structural similarity within limited regions (X and Y) implicated in catalysis.
      The role of residues contained within a highly conserved sequence present in the
      X region was investigated by site-directed mutagenesis of PLC-delta 1 isoenzyme.
      Seven residues (Ser-308, Ser-309, Ser-310, His-311, Thr-313, Tyr-314, and Gln
      319) were individually replaced by alanine or glutamine (His-311). Replacement of
      two residues, His-311 and Tyr-314, resulted in a dramatic reduction of enzyme
      activity. The kcat of hydrolysis of phosphatidylinositol 4,5-bisphosphate by
      H311A and Y314A mutants was reduced 1000- and 10-fold respectively, with little
      effect on Km. Further analysis of H311A and Y314A mutants, using limited
      proteolysis and circular dichroism, had shown that no major structural
      alterations had occurred. Since site-directed mutagenesis demonstrated the
      importance of histidine residues, their role in enzyme function was also analysed
      by chemical modification with diethyl pyrocarbonate. This modification of
      histidine residues resulted in the reduction of enzyme activity and also
      indicated that more than one residue could be important.

PMID- 7717995
TI  - Regulation of fibroblast procollagen production. Transforming growth factor-beta
      1 induces prostaglandin E2 but not procollagen synthesis via a pertussis toxin
      sensitive G-protein.
AB  - Transforming growth factor-beta 1 (TGF beta 1) initiates a series of signalling
      events resulting in diverse cellular responses including stimulation of
      extracellular matrix protein production. In this study we have investigated the
      role of pertussis toxin-sensitive G-proteins in mediating the effects of TGF beta
      1 on fibroblast procollagen metabolism. TGF beta 1 stimulated human fetal lung
      fibroblast procollagen synthesis and production in a dose-dependent manner which
      was maximal at 0.5 ng/ml. TGF beta 1 also decreased the proportion of newly
      synthesized procollagen degraded intracellularly. Pertussis toxin, a G-protein
      inhibitor, further stimulated TGF beta 1-induced procollagen synthesis and
      production, but alone it had no effect on fibroblast procollagen metabolism.
      Addition of indomethacin also potentiated the TGF beta 1-induced increase in
      procollagen synthesis and production. The effects of pertussis toxin and
      indomethacin were not additive. Pertussis toxin and indomethacin did not affect
      the proportion of newly synthesized procollagen degraded intracellularly, either
      alone or in combination, by control cells. The TGF beta 1-induced decrease in
      intracellular procollagen degradation was maintained but not further affected by
      pertussis toxin or indomethacin. TGF beta 1 increased prostaglandin E2 (PGE2)
      compared with PGE2 production by control cells. Addition of pertussis toxin or
      indomethacin blocked the TGF beta 1-induced increase in PGE2 production. The TGF
      beta 1-induced increase in PGE2 preceded the increase in procollagen production.
      These results demonstrate that TGF beta 1-induced procollagen synthesis by lung
      fibroblasts is modulated by production of PGE2. Pertussis toxin and indomethacin
      block the production of PGE2 and enhance the effect of TGF beta 1 on procollagen
      synthesis. From these data we conclude that the effects of TGF beta 1 on PGE2
      production but not procollagen synthesis are mediated via a receptor linked to a
      pertussis toxin-sensitive G-protein.

PMID- 7717997
TI  - Expression, purification and characterization of 1-aminocyclopropane-1
      carboxylate oxidase from tomato in Escherichia coli.
AB  - 1-Aminocyclopropane-1-carboxylate (ACC) oxidase catalyses the final step in the
      biosynthesis of the plant hormone ethylene. The successful overexpression and
      characterization of active ACC oxidase from tomato has been achieved. PCR was
      used to insert the corrected cDNA coding for the tomato ACC oxidase into the pET
      11a expression vector. Cloning of the resultant construct in Escherichia coli
      BL21(DE3)pLysE gave transformants which expressed ACC oxidase at levels greater
      than 30% of soluble protein under optimized conditions. When induced by addition
      of isopropyl-beta-D-thiogalactopyranoside (IPTG) at 37 degrees C the ACC oxidase
      expressed was less soluble and less active than when induced at 27 degrees C. The
      enzyme was purified to near homogeneity by a three-step chromatographic
      procedure. The specific activity of the purified recombinant ACC oxidase was
      typically 1.3-1.9 mol of ethylene/mol of enzyme per min, higher than values
      reported for native enzyme. Like the native enzyme it displayed a requirement for
      ferrous iron and ascorbate, and CO2 was an activator. The ability to discriminate
      between racemic diastereomers of 1-amino-2-ethyl cyclopropane-1-carboxylic acid
      was demonstrated. The enzyme was found to have a loose specificity for ascorbate,
      showing apparent preference for D-ascorbate and 5,6-O-isopropylidene L-ascorbate
      rather than L-ascorbate. The addition of catalase, dithiothreitol and BSA to
      incubation mixtures all resulted in significant increases in activity. When
      treated with diethylpyrocarbonate (DEPC) under mildly acidic conditions, the
      enzyme rapidly lost activity. Comparison of the rate of inactivation with the
      increase in absorbance at 240 nm gave results consistent with the modification of
      two to three histidine residues at the active site, although the possibility of
      additional modification of other nucleophilic residues cannot be excluded.
      Inactivation was largely prevented by the addition of substrates and ferrous
      iron, implying that DEPC treatment results in the modification of active-site
      histidines, which act as ligands for ferrous iron. CO2 offered no protection
      against DEPC inactivation, either in the absence or presence of substrates and/or
      ferrous iron.

PMID- 7718001
TI  - Mechanisms of autoimmune disease induction. The role of the immune response to
      microbial pathogens.

PMID- 7718000
TI  - Contribution of the mitochondrial permeability transition to lethal injury after
      exposure of hepatocytes to t-butylhydroperoxide.
AB  - We have developed a novel method for monitoring the mitochondrial permeability
      transition in single intact hepatocytes during injury with t-butylhydroperoxide
      (t-BuOOH). Cultured hepatocytes were loaded with the fluorescence probes, calcein
      and tetramethylrhodamine methyl ester (TMRM). Depending on loading conditions,
      calcein labelled the cytosolic space exclusively and did not enter mitochondria
      or it stained both cytosol and mitochondria. TMRM labelled mitochondria as an
      indicator of mitochondrial polarization. Fluorescence of two probes was imaged
      simultaneously using laser-scanning confocal microscopy. During normal
      incubations, TMRM labelled mitochondria indefinitely (longer than 63 min), and
      calcein did not redistribute between cytosol and mitochondria. These findings
      indicate that the mitochondrial permeability transition pore ('megachannel')
      remained closed continuously. After addition of 100 microM t-BuOOH, mitochondria
      filled quickly with calcein, indicating the onset of mitochondrial permeability
      transition. This event was accompanied by mitochondrial depolarization, as shown
      by loss of TMRM. Subsequently, the concentration of ATP declined and cells lost
      viability. Trifluoperazine, a phospholipase inhibitor that inhibits the
      permeability transition in isolated mitochondria, prevented calcein
      redistribution into mitochondria, mitochondrial depolarization, ATP depletion and
      cell death. Carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial
      uncoupler, also rapidly depolarized mitochondria of intact hepatocytes but did
      not alone induce a permeability transition. Trifluoperazine did not prevent ATP
      depletion and cell death after the addition of CCCP. In conclusion, the
      permeability transition pore does not 'flicker' open during normal incubation of
      hepatocytes but remains continuously closed. Moreover, mitochondrial
      depolarization per se does not cause the permeability transition in intact cells.
      During oxidative stress, however, a permeability transition occurs quickly which
      leads to mitochondrial depolarization and cell death.

PMID- 7717998
TI  - Cloning, expression and chromosomal localization of the rat pancreatitis
      associated protein III gene.
AB  - PAP III belongs to the family of pancreatitis-associated proteins, recently
      characterized as pancreatic secretory proteins structurally related to C-type
      lectins, and whose expression is induced during the acute phase of pancreatitis.
      In this paper, we describe the cloning, characterization and chromosomal
      localization of the rat PAP III gene. The gene was isolated from a genomic
      library using a PCR-based method and characterized over 2.5 kb of gene sequence
      and 1.7 kb of 5'-flanking sequence. The 5' end of the coding sequence was
      determined by primer extension of the PAP III transcript. The PAP III coding
      sequence spanned over six exons. We found striking similarities between PAP III
      and PAP I and II genes, in genomic organization as well as in promoter sequences.
      Moreover, the rat PAP III gene was mapped to chromosome 4 using mouse-rat hybrid
      cells, a localization which coincides with that of the PAP I and II genes. The
      three genes could therefore derive from the same ancestral gene by duplication.
      Expression of the PAP III gene was compared with that of PAPs I and II.
      Expression levels were similar in pancreas, where PAP III mRNA concentration
      increased within 6 h following induction of pancreatitis, reached maximal levels
      (> 200 times control values) at 24-48 h, and decreased thereafter. In the
      intestinal tract, where PAP II is not expressed, the pattern of PAP III
      expression was comparable with that of PAP I; fasting induced a decrease in its
      mRNA concentration by more than 80%, which could be reversed within 6 h upon
      feeding. PAP III is therefore a new member of the PAP gene family, more closely
      related to the PAP I gene.

PMID- 7717999
TI  - Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open
      upon reperfusion.
AB  - 1. The yield of mitochondria isolated from perfused hearts subjected to 30 min
      ischaemia followed by 15 min reperfusion was significantly less than that for
      control hearts, and this was associated with a decrease in the rates of ADP
      stimulated respiration. 2. The presence of 0.2 microM cyclosporin A (CsA) in the
      perfusion medium during ischaemia and reperfusion caused mitochondrial recovery
      to return to control values, but did not reverse the inhibition of respiration.
      3. A technique has been devised to investigate whether the Ca(2+)-induced non
      specific pore of the mitochondrial inner membrane opens during ischaemia and/or
      reperfusion of the isolated rat heart. The protocol involved loading the heart
      with 2-deoxy[3H]glucose ([3H]DOG), which will only enter mitochondria when the
      pore opens. Subsequent isolation of mitochondria demonstrated that [3H]DOG did
      not enter mitochondria during global isothermic ischaemia, but did enter during
      the reperfusion period. 4. The amount of [3H]DOG that entered mitochondria
      increased with the time of ischaemia, and reached a maximal value after 30-40 min
      of ischaemia. 5. CsA at 0.2 microM did not prevent [3H]DOG becoming associated
      with the mitochondria, but rather increased it; this was despite CsA having a
      protective effect on heart function similar to that shown previously [Griffiths
      and Halestrap (1993) J. Mol. Cell. Cardiol. 25, 1461-1469]. 6. The non
      immunosuppressive CsA analogue [MeAla6]cyclosporin was shown to have a similar Ki
      to CsA on purified mitochondrial peptidyl-prolyl cis-trans-isomerase and
      mitochondrial pore opening, and also to have a similar protective effect against
      reperfusion injury. 7. Using isolated heart mitochondria, it was demonstrated
      that pore opening could become CsA-insensitive under conditions of adenine
      nucleotide depletion and high matrix [Ca2+] such as may occur during the initial
      phase of reperfusion. The apparent increase in mitochondrial [3H]DOG in the CsA
      perfused hearts is explained by the ability of the drug to stabilize pore closure
      and so decrease the loss of [3H]DOG from the mitochondria during their
      preparation.

PMID- 7718002
TI  - Complement components C1q, C1r/C1s, and C1INH in rheumatoid arthritis.
      Correlation of in situ hybridization and northern blot results with function and
      protein concentration in synovium and primary cell cultures.
AB  - OBJECTIVE: To analyze the synovial site and the cell types expressing C1q,
      C1r/C1s, and C1-esterase inhibitor (C1INH) and to characterize newly synthesized
      C1q in patients with rheumatoid arthritis (RA). METHODS: Tissue and primary cell
      cultures of synovium from RA patients were analyzed for C1q, C1r/C1s, and C1INH
      by Northern blotting, in situ hybridization, and pulse-chase experiments for C1q.
      RESULTS: The de novo synthesis of C1q, C1r/C1s, and C1INH in synovium and primary
      cell cultures was proven by Northern blot and by antigenic and functional
      analysis. In in situ hybridization experiments, the synovial lining cell layer
      was identified as the site of C1q, C1r, and C1INH expression. In contrast,
      immunohistologic analysis showed that C1q, C1s, and C1INH proteins were present
      in a thin film covering the synovial lining cells. In situ hybridization
      performed on primary cell cultures provided evidence that only macrophages were
      able to express C1q, whereas fibroblasts and stellate cells synthesized C1r.
      CONCLUSION: The synovium is important for the synthesis and secretion of C1q and
      C1r/C1s, as well as the control protein C1INH, which supports the idea of a
      locally occurring inflammatory process in RA patients.

PMID- 7718003
TI  - Use of immunohistologic and in situ hybridization techniques in the examination
      of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis.
AB  - OBJECTIVE: To investigate mechanisms involved in inflammation and new bone
      formation in the sacroiliac (SI) joints of patients with ankylosing spondylitis
      (AS). PATIENTS AND METHODS: Computed tomography-assisted biopsy of the SI joint
      was performed in 5 patients with AS with a mean disease duration of 4.5 years and
      radiographic stage 2-3 disease. Immunohistologic studies were performed with the
      alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger
      RNA (mRNA) was detected by in situ hybridization. RESULTS: Dense cellular
      infiltrates with varying amounts of CD3+ cells (mean +/- SD 53.3 +/- 24.1%), CD4+
      cells (29.7 +/- 17.6%), CD8+ cells (15.8 +/- 11.4%), CD14+ cells (23.6 +/-
      16.9%), CD45RO+ cells (48.4 +/- 23.6%), and CD45RA+ cells (4.5 +/- 2.9%) were
      found in the synovial portion of the SI joints of all 5 patients. In these
      infiltrates a high amount of tumor necrosis factor alpha (TNF alpha) mRNA and,
      near the site of new bone formation, a lower amount of transforming growth factor
      beta (TGF beta) mRNA, were detected, while no message for interleukin-1 was found
      in the 3 patients examined by this technique. CONCLUSION: The presence of T cells
      and macrophages was demonstrated in cellular infiltrates in the SI joints of 5
      patients with active AS. The finding of abundant TNF alpha message in these
      joints could have implications regarding potential immunotherapeutic approaches
      to this disease. TGF beta might be involved in new bone formation in AS.

PMID- 7718004
TI  - Impaired polyclonal T cell cytolytic activity. A possible risk factor for
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether impaired generation of polyclonal T cell
      cytolytic activity is over-represented in systemic lupus erythematosus (SLE)
      compared with other rheumatologic diseases and whether such impaired generation
      of cytolytic activity waxes and wanes with disease activity and/or changes in
      medications. METHODS: Peripheral blood mononuclear cells from 84 SLE patients, 55
      rheumatologic disease (RD) controls, and 44 normal subjects were stimulated with
      anti-CD3 monoclonal antibody, maintained in interleukin-2, and assayed for
      cytolytic activity against 51Cr-labeled Daudi target cells. RESULTS: Generation
      of cytolytic activity was significantly lower in SLE patients than in either RD
      or normal controls. Abnormal cytolytic responses in SLE could not be attributed
      to the patient's sex, race, age, disease activity, or antirheumatic medications
      (including corticosteroids and cytotoxics), although both SLE and RD patients
      taking azathioprine (AZA) manifested lower responses than did corresponding
      patients not taking AZA. Abnormal cytolytic activity reflected, in large measure,
      impaired cytolytic activity of CD8+ T cells. No significant difference in the
      generation of cytolytic activity between RD and normal controls was detected.
      CONCLUSION: Impaired generation of polyclonal T cell cytolytic activity may be a
      predisposing factor in the development of SLE.

PMID- 7718006
TI  - Increased proteoglycan synthesis in cartilage in experimental canine
      osteoarthritis does not reflect a permanent change in chondrocyte phenotype.
AB  - OBJECTIVE: To determine whether chondrocytes in early experimental osteoarthritic
      (OA) cartilage continue to show increased synthesis and turnover of proteoglycans
      (PGs) during explant culture. A comparison was also made between the
      responsiveness of experimental OA and control cartilage to interleukin-1 beta (IL
      1 beta) and tumor necrosis factor alpha (TNF alpha) after 1 day and 3 days in
      culture. METHODS: OA was induced in mature animals by sectioning of the anterior
      cruciate ligament followed by 3 months of normal exercise. PG synthesis in the
      articular cartilage was determined by measuring 35S-sulfate incorporation during
      explant culture over 1-3 days. Inhibition of PG synthesis was also determined
      with various concentrations of IL-1 beta and TNF alpha after 1 and 3 days in
      culture. PGs extracted from the articular cartilage over 1-3 days in culture were
      examined by agarose-polyacrylamide gel electrophoresis. RESULTS: Up to 24 hours
      after excision from the joint, PG synthesis was higher in experimental OA
      cartilage than in control cartilage. It was also less sensitive to inhibition by
      TNF alpha. These differences were no longer detected after 48-72 hours in
      culture. There were no changes in the relative proportions of aggrecan and
      decorin/biglycan extracted from and synthesized by control and experimental OA
      cartilage over the 3 days in culture. CONCLUSION: Previous results indicated that
      PG synthesis and turnover in articular cartilage was increased for many months
      after induction of experimental OA. Our present results show that the enhanced
      rate of PG synthesis and turnover were evident in freshly explanted tissue, but
      the differences were lost over 3 days in culture. A decreased responsiveness to
      TNF alpha was also lost. The hypermetabolic activity of experimental OA
      chondrocytes was thus reversible and not a permanent change in chondrocyte
      phenotype.

PMID- 7718007
TI  - Critical appraisal of continuing medical education in the rheumatic diseases for
      primary care physicians.
AB  - OBJECTIVE: To critically appraise evidence of the effectiveness of continuing
      medical education (CME) in rheumatic diseases for primary care physicians.
      METHODS: Three physicians independently applied preset criteria to evaluated CME
      interventions published between January 1966 and August 1993. RESULT: Eight of
      166 articles identified were critically appraised, 7 of which had positive
      results. Marked heterogeneity in educational interventions, evaluative methods,
      and outcomes was noted. CONCLUSION: Despite generally positive results, weak
      methodology precludes drawing firm conclusions about the effectiveness of CME in
      rheumatic diseases.

PMID- 7718005
TI  - Cross-linked elastin and collagen degradation products in the urine of patients
      with scleroderma.
AB  - OBJECTIVE: To measure the urinary excretion of specific cross-link amino acid
      markers for mature elastin (desmosine [DES] and isodesmosine [IDES]) and
      fibrillar collagen (hydroxylysylpyridinoline [HP] and lysylpyridinoline [LP]) in
      systemic sclerosis (SSc) patients and healthy controls. METHODS: Urine specimens
      from 20 patients with SSc and 22 controls were assessed for DES, IDES, HP, and LP
      using high performance liquid chromatography and ultraviolet absorption
      spectroscopy, in combination with an isotope dilution technique in which the
      urine specimen was spiked with isotopically labeled cross-link amino acids.
      RESULTS: Mean +/- SD levels of urinary DES and IDES were elevated in SSc patients
      by 2-3-fold, and urinary HP and LP by 3-4-fold, compared with controls (DES 21.0
      +/- 9.4 versus 7.5 +/- 1.4 micrograms/gm creatinine; HP 109.0 +/- 72.9 versus
      24.9 +/- 5.7 nmoles/mmole creatinine). Nineteen of the 20 SSc patients had
      urinary DES and HP values that were > 3 SD above the control mean. A significant
      elevation in the HP:LP ratio in SSc patients as compared with controls (mean +/-
      SD 6.9 +/- 1.5 versus 5.5 +/- 1.3) indicated a soft tissue origin for much of the
      increased HP. CONCLUSION: Patients with SSc have higher levels of urinary cross
      link amino acids specific for the degradation of mature collagen and elastin.
      These markers distinguish most SSc patients from healthy controls.

PMID- 7718008
TI  - Knee osteoarthritis in former runners, soccer players, weight lifters, and
      shooters.
AB  - OBJECTIVE: To determine the relationship between different physical loading
      conditions and findings of knee osteoarthritis (OA). METHODS: We selected 117
      male former top-level athletes (age range 45-68 years) who had participated in
      sports activities with distinctly different loading conditions: 28 had been long
      distance runners, 31 soccer players, 29 weight lifters, and 29 shooters.
      Histories of lifetime occupational and athletic knee loading, knee injuries, and
      knee symptoms were obtained, and subjects were examined clinically and
      radiographically for knee findings of OA. RESULTS: The prevalence of tibiofemoral
      or patellofemoral OA based on radiographic examination was 3% in shooters, 29% in
      soccer players, 31% in weight lifters, and 14% in runners (P = 0.016 between
      groups). Soccer players had the highest prevalence of tibiofemoral OA (26%), and
      weight lifters had the highest prevalence of patellofemoral OA (28%). Subjects
      with radiographically documented knee OA had more symptoms, clinical findings,
      and functional limitations than did subjects without knee OA. By stepwise
      logistic regression analysis, the risk for having knee OA was increased in
      subjects with previous knee injuries (odds ratio [OR] 4.73), high body mass index
      at the age of 20 (OR 1.76/unit of increasing body mass index), previous
      participation in heavy work (OR 1.08/work-year), kneeling or squatting work (OR
      1.10/work-year), and in subjects participating in soccer (OR 5.21). CONCLUSION:
      Soccer players and weight lifters are at increased risk of developing premature
      knee OA. The increased risk is explained in part by knee injuries in soccer
      players and by high body mass in weight lifters.

PMID- 7718010
TI  - The prevalence and incidence of systemic lupus erythematosus in Birmingham,
      England. Relationship to ethnicity and country of birth.
AB  - OBJECTIVE: To establish the point prevalence of systemic lupus erythematosus
      (SLE) on January 1, 1992, and the incidence of SLE during 1991, in Birmingham,
      England, a large city with a broad ethnic mix. METHODS: Six sources were used to
      ascertain patients with diagnosed SLE, including notification by attending and
      primary care physicians, the lupus patient support group, and hospital inpatient
      and laboratory data. RESULTS: There were 242 SLE patients (227 females, 15 males)
      identified: prevalence rate 27.7/100,000 (95% confidence interval 24.2
      31.2/100,000) in the population and 206.0/100,000 in Afro-Caribbean females. No
      significant differences in female ethnic prevalence rates by place of birth were
      observed. Thirty-three patients developed SLE in 1991: incidence rate
      3.8/100,000/year (95% confidence interval 2.5-5.1/100,000/year). CONCLUSION: This
      study illustrates dramatic differences in incidence and prevalence rates in the
      UK, depending on ethnic group and irrespective of place of birth.

PMID- 7718009
TI  - HLA-DR8 and acute anterior uveitis in ankylosing spondylitis.
AB  - OBJECTIVE: To identify possible factors in the development of acute anterior
      uveitis (AUU) in patients with ankylosing spondylitis (AS). METHODS: We
      investigated HLA antigens serologically, and HLA-DRB1*08 alleles by polymerase
      chain reaction-restriction fragment length polymorphism, in 42 Japanese AS
      patients with and without AAU. RESULTS: Thirty-six of the AS patients (85.7%) had
      HLA-B27. Thirteen (65%) of the 20 patients with AAU had HLA-DR8, whereas only 1
      (4.5%) of the 22 patients without AAU had DR8. The difference was statistically
      significant (Pcorr < 0.001). CONCLUSION: Our data suggest that HLA-B27 is
      strongly associated with AS in Japanese patients and that HLA-DR8 is important
      for the development of AAU in Japanese patients with AS.

PMID- 7718013
TI  - Gouty arthritis in the acquired immunodeficiency syndrome. An unusual but
      aggressive case.
AB  - Patients with the acquired immunodeficiency syndrome (AIDS) are
      characteristically hypouricemic. Therefore, the occurrence of gouty arthritis in
      association with AIDS would be expected to be a rare phenomenon. We describe a
      patient with AIDS in whom gouty arthritis developed. Features of both diseases in
      relation to their coexistence in this patient are discussed.

PMID- 7718011
TI  - Radiologic vignette.

PMID- 7718012
TI  - Summary of the Sixth International Conference on Lyme Borreliosis.

PMID- 7718015
TI  - Matrix metalloproteinase inhibitors in the treatment of arthritis: comment on the
      article by Vincenti et al.

PMID- 7718016
TI  - Cost and handling of parenteral methotrexate.

PMID- 7718014
TI  - Toxic epidermal necrolysis after sulfasalazine treatment of mild psoriatic
      arthritis: warning on the use of sulfasalazine for a new indication.

PMID- 7718018
TI  - The effects of fibrates on lipoprotein and hemostatic coronary risk factors.
AB  - The effects of fibrates on lipoprotein profiles and lipoprotein physiology, as
      well as on selected coagulation and fibrinolytic factors are reviewed. It is
      concluded that the action of fibrates on these systems is such as to render the
      fibrates beneficial in atherosclerosis prevention.

PMID- 7718019
TI  - Two founder mutations in the LDL receptor gene in Norwegian familial
      hypercholesterolemia subjects.
AB  - DNA from 20 unrelated familial hypercholesterolemia (FH) subjects were studied by
      analysis of single-strand conformation polymorphisms (SSCP) for mutations in exon
      3 of the low density lipoprotein (LDL) receptor gene. Four different SSCP
      patterns were observed. The underlying mutations were characterized by DNA
      sequencing. One pattern represented the wild-type sequence. Another pattern
      represented a C-->G mutation (FH-Svartor) that changes codon 78 into the amber
      stop codon. The two other patterns represented heterozygosity and homozygosity,
      respectively, for a G-->A splice donor mutation (FH-Elverum) in intron 3. Based
      upon two PCR-based assays, the frequencies of FH-Svartor and FH-Elverum among 267
      unrelated FH subjects, were 8% and 25%, respectively. FH Svartor was located on a
      chromosome with haplotype 3 in all five families where haplotype analysis were
      performed. FH Elverum was located on haplotype 2 in 16 out of 20 families. The
      two mutations must be considered founder mutations in the Norwegian population,
      and their existence will be clinically useful in diagnosing FH. The presence of
      two founder mutations together with previously published data on the prevalence
      of FH in Norway, indicate that FH may be a more common disease in Norway than
      previously thought.

PMID- 7718017
TI  - Parenteral methotrexate: effective shelf-life following initial puncture of
      preservative-protected vial.

PMID- 7718020
TI  - Effect of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitor, on hepatic cholesterol 7 alpha-hydroxylase, acyl-coenzyme A:
      cholesterol acyltransferase, and bile lipid secretion in the hamster with intact
      enterohepatic circulation.
AB  - The effects of administration of pravastatin, a 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, on hepatic cholesterol 7 alpha
      hydroxylase and acyl-coenzyme A: cholesterol acyltransferase (ACAT) activities
      and bile lipid secretion were investigated in Syrian golden hamsters. Continuous
      administration of pravastatin induced no significant changes in hepatic
      cholesterol content, ACAT and cholesterol 7 alpha-hydroxylase activities, or bile
      lipid and acid composition. Abrupt withdrawal of pravastatin induced increases in
      hepatic cholesterol content and ACAT activity and no change in hepatic
      cholesterol 7 alpha-hydroxylase activity, and increased cholesterol saturation in
      bile. Hepatic cholesterol 7 alpha-hydroxylase activity paralleled hepatic mRNA
      levels of this enzyme. These results suggest that a change in hepatic cholesterol
      metabolism induced by continuous administration of pravastatin maintains a
      constant net balance of hepatic cholesterol content. In addition, the drug has no
      deleterious influence on metabolism of bile lipids and acids and related enzymes,
      except for a transient increase in cholesterol saturation in bile induced by an
      inappropriate increase in hepatic cholesterol content and a lack of response of
      cholesterol 7 alpha-hydroxylase activity to changes in hepatic cholesterol
      content upon abrupt withdrawal of pravastatin.

PMID- 7718021
TI  - Plasma low density lipoprotein cholesterol concentration in cynomolgus monkeys;
      differing effects of age and body weight in animals consuming low and high
      cholesterol diets.
AB  - It has been reported in cross-sectional studies that plasma cholesterol
      concentration does not increase with age in nonhuman primates who consume a
      cholesterol-free diet over their lifetimes. However, dietary composition and body
      weight may confound any change in plasma cholesterol concentration during aging,
      as is the case in humans in industrialized societies. To determine if the
      relationship between age and plasma cholesterol concentration is affected by
      dietary cholesterol and body weight in nonhuman primates, we compared post
      pubertal male cynomolgus monkeys consuming low cholesterol (0.04 mg
      cholesterol/kcal; n = 10) and high cholesterol (0.39 mg cholesterol/kcal: n = 21)
      diets. A univariate repeated measures analysis of covariance of low density
      lipoprotein (LDL) cholesterol concentration was performed from a longitudinal
      data set (monkeys aged 5 to 20 years), containing an average of 34 observations
      per animal. The interaction of age and body weight on LDL cholesterol
      concentration differed among the two dietary groups. In monkeys consuming the low
      cholesterol diet, an increase in age was associated with a small increase in mean
      LDL cholesterol concentration. This effect of age increased with increasing body
      weight. Monkeys on the high cholesterol diet had higher mean LDL concentration,
      but showed no significant effect of aging on concentration. Instead, at all ages,
      LDL concentration was strongly affected (positively) by body weight in this
      group. A qualitatively similar (but quantitatively smaller) effect of body weight
      was observed only at older ages in the low dietary cholesterol group. We conclude
      that the associations of LDL concentration with age and body weight in cynomolgus
      monkeys are strongly influenced by dietary cholesterol.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7718022
TI  - Plasma phospholipid fatty acid composition and factor VII coagulant activity.
AB  - Plasma phospholipid fatty acid composition reflects, to a moderate degree, the
      fatty acid composition of the diet. To determine whether plasma phospholipid
      fatty acid composition might influence factor VII coagulant activity (factor
      VIIc), we examined 2207 middle-aged adults free of diabetes and cardiovascular
      disease. Factor VIIc was associated positively with the percentage of fatty acids
      that was saturated, and it was associated negatively with the linoleic acid
      percentage and the phospholipid polyunsaturated/saturated fatty acid ratio. For
      example, a 1.9% greater saturated fatty acid level was associated with
      approximately a 5% higher factor VIIc. These results suggest a role for dietary
      fat composition, or related dietary patterns, in determining levels of factor
      VIIc.

PMID- 7718024
TI  - Phenotypic expression and frequency of familial defective apolipoprotein B-100 in
      Belgian hypercholesterolemics.
AB  - DNA screening for apolipoprotein (apo) B mutations causing familial defective
      apolipoprotein B-100 (FDB) was performed in 87 hyperlipidemic Belgian individuals
      using heteroduplex analysis. Eighteen FDB heterozygotes from 5 unrelated families
      were identified. Three of the index cases reported an early family history of
      premature coronary heart disease (CHD). The frequency of the apo B3500 mutation
      was 8% in Belgians with type IIa hyperlipidemia, indicating that the prevalence
      of FDB may be as high as 1 in 250 in the general Belgian population. Plasma lipid
      levels of the patients identified in the present study are similar to those
      previously reported for FDB heterozygotes. We compared these data with results
      obtained in a genotype/phenotype correlation study of heterozygous familial hyper
      cholesterolemia (FH) in the Afrikaner population of South Africa. Plasma
      cholesterol levels in FDB heterozygotes were similar to those reported for FH
      heterozygotes with defective receptors (Asp206-->Glu, approximately 20% normal
      receptor activity), but significantly lower than in FH heterozygotes with a
      mutant protein which virtually lacks receptor activity (Val408-->Met, < 2% normal
      receptor activity). FDB appears to be a significant genetic cause of
      hypercholesterolemia in Belgium.

PMID- 7718025
TI  - Reduced smooth muscle cell regeneration in Yoshida (YOS) spontaneously
      hypercholesterolemic rats.
AB  - Hypercholesterolemia is a predisposing factor for atherosclerosis. We studied the
      response to damage of vascular smooth muscle cells (SMC) from
      normocholesterolemic Brown Norway (BN) and from spontaneously hyper
      cholesterolemic Yoshida (YOS) rats (16-24 month old). The regrowth rate of SMC
      from BN and YOS rats after freeze-induced damage was similar in the presence of
      fetal calf serum and of serum derived from normocholesterolemic rats, while it
      was reduced in the presence of serum from hypercholesterolemic rats. Freeze
      injury of the abdominal aorta was followed by reduced neointima formation in YOS
      rats, as compared to BN rats, confirming the impaired response of vascular cells
      from hypercholesterolemic rats to injury. This defect may be due either to lipids
      or to unknown factors present in the hyperlypidemic serum.

PMID- 7718026
TI  - Relations of life-style with lipids, blood pressure and insulin in adolescents
      and young adults. The Cardiovascular Risk in Young Finns Study.
AB  - The associations of life-style variables, namely type of dietary fat, alcohol
      use, smoking, obesity, physical activity and oral contraceptive use with serum
      lipids, insulin and blood pressure were studied in 1398 adolescents and young
      adults aged 15-24 years. Smokers were more often physically inactive and regular
      users of alcohol compared to non-smokers. In females, smoking and alcohol use
      were more prevalent among oral contraceptive users. Independent effects of life
      style variables on lipids, blood pressure and insulin were assessed with multiple
      linear regression models. In both sexes, body mass index was positively related
      to low density lipoprotein cholesterol (LDL-C), triglycerides (TG), systolic
      (SBP) and diastolic (DBP) blood pressure and insulin, and negatively with high
      density lipoprotein cholesterol (HDL-C). Leisure time physical activity was
      associated with lower levels of insulin among males. Smoking was related with
      0.07 mmol/l lower HDL-C levels and about 0.09 mmol/l higher TG levels in males.
      In both sexes, smoking was related with lower levels of SBP. In males, alcohol
      use was associated with 0.05 mmol/l higher level of HDL-C (P = 0.06). In females,
      alcohol use was associated with lower levels of LDL-C and TG. Oral contraceptive
      use was associated with approximately 0.15 mmol/l higher levels of TG and about
      4.0 mmHg higher SBP. Preferring butter over margarine as dietary fat was
      associated with 0.26 and 0.19 mmol/l higher levels of LDL-C in males and females,
      respectively. Accumulation of adverse life-habits contributed to the clustering
      of an atherogenic lipid profile and high blood pressure. In males, those with 4
      selected life-habits present, namely obesity, smoking, inactivity and the use of
      butter, had 5.5 times greater risk (95% confidence interval 1.4-20.7) of
      belonging to the group with high LDL-C, low HDL-C and high DBP compared to those
      with zero or one life-habits present. These data demonstrate that life-habits
      show clustering in adolescents and young adults. Individuals with many adverse
      life-style risk factors present are at increased risk of having an atherogenic
      lipid and blood pressure profile.

PMID- 7718023
TI  - Detection of a single base deletion in codon 424 of the low density lipoprotein
      receptor gene in a Danish family with familial hypercholesterolemia.
AB  - We performed a screening of exon 9 of the low density lipoprotein receptor (LDLR)
      gene in 14 Danish families with familial hypercholesterolemia (FH) using the
      denaturing gradient gel electrophoresis (DGGE) technique. In one of the probands
      from these families an abnormal band pattern in the gradient gel was detected.
      Subsequent DGGE analysis of the family of this index patient revealed that the
      DGGE pattern cosegregated with the disease in this family. Sequencing of the exon
      showed a deletion of a C in codon 424 of the LDLR gene resulting in a frame shift
      with the introduction of a stop codon 5 codons further downstream. The mutation
      is referred to as FH-Odense. The predicted truncated receptor protein consists of
      the 428 amino terminal amino acids. Consequently, the cytosolic and membrane
      spanning parts of the mature LDL receptor, which normally secure the receptor in
      the plasma membrane, are missing. The FH-Odense mutation results in severe
      premature coronary atherosclerosis as shown by the clinical expression in 5
      generations of the affected family.

PMID- 7718027
TI  - Increase in epsilon(gamma-glutamyl)lysine crosslinks in atherosclerotic aortas.
AB  - Portions of aortas from normal and atherosclerotic rabbits and from human autopsy
      subjects were washed and separated into layers which were subjected to exhaustive
      proteolytic digestion. The digests were assayed for epsilon(gamma-glutamyl)lysine
      crosslinks by a two-stage high performance liquid chromatography (HPLC)
      procedure. Crosslink concentrations in intima-media from rabbits where more than
      15% of the aorta lumen surface was lesioned are greater than in normal aortas or
      aortas with less than 15% of the surface lesioned. Higher crosslink
      concentrations occur in fibrolipid plaques from human aortas than in intima-media
      layers of equal thickness from non-lesioned areas of the same aortas. Much of the
      crosslink in fibrolipid plaques occurs in the proteins which float at d < 1.18
      g/ml. Non-lesioned areas of intima-media from aortas with fatty streaks or
      plaques have higher crosslink concentrations than intima-media from aortas with
      no lesions. In normal and lesioned intimas thinner than 0.2 mm, the concentration
      of the crosslink is lower than in the subjacent media. These findings indicate
      that increased epsilon(gamma-glutamyl)lysine crosslinking occurs in the
      atherosclerotic aorta and is associated principally with smooth muscle cells. It
      is suggested that the crosslinked products may be involved in retention of
      lipoproteins and the increase in collagen production.

PMID- 7718028
TI  - Protein glycation and fluorescent material in human atheroma.
AB  - Samples of normal human aorta, atherosclerotic lesions and atheroma (necrotic
      'gruel' from the interior of advanced lesions) were obtained at necropsy from
      subjects with no history of diabetes mellitus. Components of each were extracted
      by ethanol:diethylether (3:1) and, subsequently, by 10% sodium dodecyl sulphate
      (SDS). Both fractions, organic and aqueous (SDS), were assessed for their
      relative fluorescence (excitation: 350 nm/emission: 430 nm). The amount of early
      products of glycated protein was assessed by affinity chromatography in the SDS
      soluble fraction. Age-matched plasma samples, obtained from non-diabetic
      individuals, were also examined. Material from atherosclerotic lesions appeared
      to exhibit an inverse correlation between protein glycation and fluorescent
      material which was best reflected within the organic extract. This was not the
      case for normal aorta. A linear correlation between fluorescent material in the
      organic extract and SDS extract existed in the normal aorta alone. The only age
      dependent change was found in normal aorta in which there was an increase in SDS
      soluble fluorescence with increasing age. In plasma samples alone, protein
      glycation and protein fluorescence appeared to be linearly correlated. The
      observations are discussed in the context of the possible contribution of protein
      glycation to atherogenesis.

PMID- 7718029
TI  - High dose ascorbate supplementation fails to affect plasma homocyst(e)ine levels
      in patients with coronary heart disease.
AB  - Pharmacologic doses of folate, in the absence of clinical folate deficiency, can
      reduce plasma levels of the putatively atherothrombotic amino acid, homocysteine
      (H(e)). Data suggesting that H(e) may accumulate in experimental scurvy prompted
      us to explore the efficacy of high dose ascorbate supplementation as a H(e)
      lowering treatment, in the absence of clinical ascorbate deficiency. A
      randomized, placebo-controlled trial of 12 weeks of high dose (4.5 g/day)
      ascorbate supplementation was completed by 44 patients with established coronary
      heart disease. No significant change in mean fasting total plasma H(e) levels was
      demonstrable despite a marked increase in mean fasting plasma ascorbate levels
      amongst those patients randomized to active treatment. Ascorbate supplementation
      to prevent the development of fasting hyperhomocysteinemia may only be relevant
      at scorbutic levels of plasma ascorbate.

PMID- 7718031
TI  - Estimates of aneuploidy using multicolor fluorescence in situ hybridization on
      human sperm.
AB  - Single color fluorescence in situ hybridization (FISH) has been utilized on sperm
      to estimate nondisjunction rates for chromosomes 1, 12, 15, 16, X and Y. Using
      single-color FISH, one cannot distinguish nonhybridization from nullisomy nor
      disomy from diploidy. In order to provide an internal control, a multicolor FISH
      strategy was employed. Satellite probes specific for 13 human chromosomes were
      used on multiple semen samples from two normal donors. Two or three probes were
      hybridized simultaneously and scored by two independent observers. Over all
      experiments, 40,641 sperm were analyzed. The majority of autosomes had no
      significant difference in aneuploidy between chromosomes or between donors.
      However, a significant difference was observed for chromosome 18 between donors
      (chi 2(2) = 7.078, 0.025 < P < 0.05). Additionally, no significant difference was
      found between donors for sex chromosome aneuploidy. The frequency of sex
      chromosome aneuploidy was similar to that seen in paternally derived 47,XXY and
      47,XYY conceptuses. Furthermore, 0.15% of sperm were found to be diploid. Based
      on the results of this study, as much as 19% of all sperm may be chromosomally
      abnormal. This method proved to be useful for determining aneuploidy of human
      chromosomes in sperm and valuable in exploring whether individual differences of
      nondisjunction exist.

PMID- 7718030
TI  - Spermine-mediated casein kinase II-uptake by rat liver mitochondria.
AB  - Spermine, ubiquitous intracellular polyamine, is able to promote the
      transmembrane translocation of casein kinase CKII through the outer membrane of
      rat liver mitochondria and its binding to more internal mitochondrial structures.
      These findings suggest that spermine may play a critical role in regulating the
      subcellular distribution of casein kinase CKII.

PMID- 7718032
TI  - Perioperative recognition, management, and pathologic diagnosis of transfusion
      related acute lung injury.

PMID- 7718033
TI  - Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction:
      insights from studies of vascular biology.
AB  - Myocardial infarction is the most frequent cause of mortality in the United
      States as well as in most western countries. In this review, the processes
      leading to myocardial infarction are described based on the most recent studies
      of vascular biology; in addition, evolving strategies for prevention are
      outlined. The following was specifically discussed. (1) Five phases of the
      progression of coronary atherosclerosis (phases 1 to 5) and eight morphologically
      different lesions (types I, II, III, IV, Va, Vb, Vc, and VI) in the various
      phases are defined. (2) The present understanding of the pathogenesis of each of
      the phases of progression and of the various lesion types preceding myocardial
      infarction is described; particular emphasis is placed on the physical,
      structural, cellular, and chemical characteristics of the "vulnerable or unstable
      plaques" prone to disruption (types IV and Va lesions). (3) The fate of plaque
      disruption (type VI lesion) in the genesis of the various coronary syndromes and
      especially acute myocardial infarction is defined; particular emphasis is placed
      on the combination of plaque disruption and a high thrombogenic risk profile-
      local factors (ie, degree of plaque disruption, exposure of lipid-macrophage-rich
      plaque, etc) and systemic factors (ie, catecholamines, RAS, fibrinogen, etc)--in
      the genesis of myocardial infarction. (4) Strategies of regression or
      stabilization of "vulnerable or unstable plaques" for prevention of myocardial
      infarction are presented within the context of recent favorable experience with
      risk factor modification and lipid-modifying angiographic trials, beta-blockade
      and angiotensin-converting enzyme inhibition, antithrombotic strategies, and the
      possible role of estrogens. The recent past has been very fruitful in yielding a
      better understanding of the processes leading to myocardial infarction, and the
      near future appears very promising in terms of preventing the number 1 killer in
      the western world.

PMID- 7718034
TI  - Cardiovascular effects of cyclosporine A and OG 37-325 after chronic
      administration to conscious rats: role of endothelin.

PMID- 7718035
TI  - Delta opioid receptor selective ligands; DPLPE-deltorphin chimeric peptide
      analogues.
AB  - Further efforts to correlate the topography of the bioactive structures of DPDPE
      and the deltorphins, two delta-opioid receptor active peptide families, are
      reported. A number of DPLPE-deltorphin chimeric peptides have been synthesized in
      which the C-terminal dipeptide delta-address of the deltorphins (-Val-GlyNH2, 
      Nle-GlyNH2) have been linked to the highly delta-opioid selective cyclic peptides
      DPDPE or DPLPE. These studies demonstrate that a major structural feature
      determining high potency of hybrid analogues is the chirality of the amino acid
      residue in position 5. The radioligand binding assays have revealed a decrease in
      potency (compared to DPDPE) at delta-receptors when the C-terminal dipeptides
      were added to DPDPE. On the other hand, chimeric peptides of DPLPE with these
      same C-terminal dipeptides retained high delta-selectivity and affinity. Similar
      results were obtained using the mouse vas deferens (MVD) and guinea pig ileum
      (GPI) bioassays. The importance of the hydrophilicity of amino acids in positions
      2 and 5 for delta-selectivity is consistent with the previous finding for DPLPE
      and DPDPE. On the other hand, the replacement of phenylalanine-4 with p
      chlorophenylalanine-4 did not increase delta-selectivity as in DPDPE. These
      findings suggest that the delta-receptor interacts with hybridized enkephalins
      and deltorphins somewhat differently than with DPDPE.

PMID- 7718037
TI  - Apolipoprotein E in Creutzfeldt-Jakob disease.

PMID- 7718039
TI  - A new type of brachial plexus lesion to be added to the classical types.

PMID- 7718036
TI  - The molecular basis of the host specificity of the Rhizobium bacteria.
AB  - The interaction between soil bacteria belonging to the genera Rhizobium,
      Bradyrhizobium and Azorhizobium and leguminous plants results in the induction of
      a new plant organ, the root nodule. After invading these root nodules via
      infection threads the bacteria start to fix atmospheric nitrogen into ammonia
      which is beneficial for the host plant. This symbiotic interaction is highly host
      specific in that each rhizobial strain is able to associate with only a limited
      number of host plant species. The subject of this presentation is the molecular
      mechanism by which the bacterium determines its host-specific characteristics.
      This mechanism appears to be based on at least two stages of molecular signaling
      between the bacterium and the plant host. In the first stage, flavonoids secreted
      by the plant root induce, in a host specific way, the transcription of bacterial
      genes which are involved in nodulation, the so-called nod genes. This leads to
      the second step of the signaling system: the production and secretion of lipo
      oligosaccharide molecules by the Rhizobium bacteria. These signal molecules,
      which are acylated forms of small fragments of chitin, have various discernable
      effects on the roots of the host plants. One of these effects is the
      dedifferentiation of groups of cells located in the cortex which leads to the
      formation of nodule meristems. In their mitogenic activity the bacterial signals
      resemble several well-known plant hormones like auxins and cytokinins. However,
      there are two major differences: (i) the bacterial signals lead to the induction
      of a specific organ and (ii) they are host-specific in that only the signals
      produced by compatible bacteria are able to induce meristems. The nod genes
      determine this stage of host specificity by their essential role in the
      biosynthesis of the signal molecules. They appear to encode enzymes which are
      involved in the processes of fatty acid biosynthesis, fatty acid transfer, chitin
      synthesis and chitin modification. I will illustrate the statement that the nod
      gene products are ideal model enzymes for the study of these important processes
      because they are not needed in the free-living state of the bacteria.

PMID- 7718038
TI  - Medicine's core values. Profession needs to open itself up.

PMID- 7718041
TI  - [Stress echocardiography with dobutamine: the importance of adding atropine in
      inconclusive tests].
AB  - OBJECTIVES: To study the feasibility of adding atropine after dobutamine infusion
      in patients with known or suspected coronary artery disease not achieving 85% of
      predicted maximal heart rate. PATIENTS: We studied with dobutamine stress
      echocardiography 219 patients (174 men e 45 women; mean age +/- SD: 58 +/- 11
      years), 126 patients with a previous myocardial infarction and 93 with angor. One
      hundred and thirty three (61%) also performed coronariography. METHODS:
      Dobutamine stress echocardiography protocol consisted of a step-wise infusion of
      dobutamine from 5 micrograms/kg/min to a maximal dose of 40 micrograms/kg/min or
      until a new or a worsening wall motion abnormality, 85% of predicted maximal
      heart rate or any indication for interruption. In patients not achieving any of
      these end points, intravenous atropine was administered up to 1 mg. Patients were
      divided in two groups: Group A: infusion of dobutamine alone and Group B:
      dobutamine plus atropine. RESULTS: With this protocol the test was interrupted in
      41 patients (19%) because of adverse effects that were mild and short lived and
      resolved with discontinuation of the test. After dobutamine infusion 46% of the
      tests were nonconclusive, the majority were on beta blocker therapy. After
      atropine administration there was a significant reduction of the nonconclusive
      studies to 20% (p < 0.001). In patients with a normal rest echocardiogram the
      sensitivity and specificity of the test to diagnose significant coronary artery
      disease was respectively 89% e 100% after atropine. The capacity of the test to
      detect multivessel disease was also increased after atropine, allowing to reach a
      sensitivity of 85% and a specificity of 90%. CONCLUSIONS: Dobutamine stress
      echocardiogram supplemented with atropine is a safe and accurate method to
      diagnose significant coronary artery disease and to detect multivessel disease in
      patients with a previous myocardial infarction with rest wall motion
      abnormalities.

PMID- 7718040
TI  - Halofantrine in acute malaria.

PMID- 7718042
TI  - Assessing risk of suicide. Deal with self harm in prisons.

PMID- 7718043
TI  - Focus on Germany.

PMID- 7718044
TI  - General anaesthesia--who decides and why?

PMID- 7718045
TI  - Chaos theory and nursing revisited.

PMID- 7718046
TI  - Ambivalence toward pain: Schweitzer versus nine inch nails.

PMID- 7718047
TI  - St. Brendan's and the community: mental health services in Ireland.
AB  - 1. In Ireland, the regional administrators--including the chiefs of nursing and
      psychiatry--have as their responsibility all of the related outpatient clinics,
      day hospitals, day care centers and community residences, including all levels of
      acuity. Discharge planning becomes easier than in the United States. 2. In
      Ireland, Assessment Units are unlocked, nurses are in uniform, there is no
      equivalent of a Master's prepared clinical specialist or an advanced level Nurse
      Practitioner, and residences are integrated into neighborhoods. 3. The majority
      of chief psychiatric nurses and officers and nurse tutors in Ireland are men.
      Teaching is not a top priority of staff nurses, and nurse tutors are not involved
      regularly with students on the wards.

PMID- 7718049
TI  - Thiophosphorylated substrate analogs are potent active site-directed inhibitors
      of protein-tyrosine phosphatases.
AB  - Thiophosphotyrosyl protein and peptide substrate analogs were found to be potent
      and specific protein-tyrosine phosphatase inhibitors with IC50s in the range of
      0.2-30 microM. The analogs were based on highly reactive substrates and included
      thiophosphotyrosyl forms of reduced carboxamidomethylated and maleylated lysozyme
      and peptides based on tyrosine phosphorylation sites of lysozyme, alpha s2
      casein, and platelet-derived growth factor receptor. These analogs inhibited
      protein-tyrosine phosphatases from both the intracellular and transmembrane
      classes and from a variety of species ranging from a prokaryote (Yersinia
      enterolitica) to man. The extent of inhibition of phosphatase activity by a given
      analog varied with the phosphatase species. In contrast, protein kinases and
      protein-serine/threonine phosphatases were not significantly affected by these
      analogs. The mechanism of inhibition was investigated using rat brain protein
      tyrosine phosphatase-1 as a prototype. These studies indicated that the
      inhibition was rapid and reversible and was competitive in nature. The Ki for
      inhibition by various thiophosphotyrosyl analogs was generally proportional to
      the apparent Km for the corresponding phosphorylated substrates. Unphosphorylated
      substrate molecules were generally much weaker inhibitors than the corresponding
      thiophosphotyrosyl substrate analogs. Taken together these results point to an
      active site-directed mechanism for inhibition. These specific inhibitory probes
      could be used to study substrate binding mechanisms as well as physiological
      roles of various protein-tyrosine phosphatases.

PMID- 7718048
TI  - Identifying relevant studies for systematic reviews.
AB  - OBJECTIVE: To examine the sensitivity and precision of Medline searching for
      randomised clinical trials. DESIGN: Comparison of results of Medline searches to
      a "gold standard" of known randomised clinical trials in ophthalmology published
      in 1988; systematic review (meta-analysis) of results of similar, but separate,
      studies from many fields of medicine. POPULATIONS: Randomised clinical trials
      published in 1988 in journals indexed in Medline, and those not indexed in
      Medline and identified by hand search, comprised the gold standard. Gold
      standards for the other studies combined in the meta-analysis were based on:
      randomised clinical trials published in any journal, whether indexed in Medline
      or not; those published in any journal indexed in Medline; or those published in
      a selected group of journals indexed in Medline. MAIN OUTCOME MEASURE:
      Sensitivity (proportion of the total number of known randomised clinical trials
      identified by the search) and precision (proportion of publications retrieved by
      Medline that were actually randomised clinical trials) were calculated for each
      study and combined to obtain weighted means. Searches producing the "best"
      sensitivity were used for sensitivity and precision estimates when multiple
      searches were performed. RESULTS: The sensitivity of searching for ophthalmology
      randomised clinical trials published in 1988 was 82%, when the gold standard was
      for any journal, 87% for any journal indexed in Medline, and 88% for selected
      journals indexed in Medline. Weighted means for sensitivity across all studies
      were 51%, 77%, and 63%, respectively. The weighted mean for precision was 8%
      (median 32.5%). Most searchers seemed not to use freetext subject terms and
      truncation of those terms. CONCLUSION: Although the indexing terms available for
      searching Medline for randomised clinical trials have improved, sensitivity still
      remains unsatisfactory. A mechanism is needed to "'register" known trials,
      preferably by retrospective tagging of Medline entries, and incorporating trials
      published before 1966 and in journals not indexed by Medline into the system.

PMID- 7718050
TI  - Antisense-designed peptides: a comparative study focusing on possible complements
      to angiotensin II.
AB  - A comprehensive study of antisense peptides possibly complementary to angiotensin
      II (AII) is described. Antisense peptides of AII were designed using two
      different procedures outlined by Blalock and Root-Bernstein. Also, peptide
      complements designed to interact as homologs of AII were investigated. Three
      methods were used to detect binding between these peptides and AII. Several
      antisense-designed peptides were studied with unprotected termini to compare the
      effects of protected vs. unprotected termini. It was determined that the
      protected antisense-designed peptides derived from Root-Bernstein's methods
      interacted (high micro-molar range) directly with AII, while those protected
      antisense peptides derived from Blalock's method interacted only with the AII
      receptor. Two novel AII antagonists were discovered using this technology, a Root
      Bernstein derived unprotected complementary peptide (H2N-K-G-V-Y-M-H-A-L-CO2H)
      and a Blalock derived unprotected antisense peptide (H2N-E-G-V-Y-V-H-P-V-CO2H),
      which exhibited 5 microM and 70 nM affinity toward the AII receptor,
      respectively.

PMID- 7718052
TI  - PBL and the lessons of the past.

PMID- 7718051
TI  - Involving students in curriculum reform.

PMID- 7718053
TI  - Orientation for new faculty members.

PMID- 7718054
TI  - Managing the passive-aggressive resident.

PMID- 7718055
TI  - The difference a medical editor can make in a residency program.

PMID- 7718057
TI  - Comparing selection criteria of residency directors and physicians' employers.
AB  - In 1993, the Medical College of Pennsylvania (MCP), mindful of the rapidly
      changing environments of health care delivery, created three surveys to gather
      information from outside the school that would help the faculty plan how the
      curriculum and advising system could better prepare students and residents for
      the demands of twenty-first-century medicine. The first survey focused on the MCP
      seniors graduating that year and asked about their perceptions of their medical
      education and their specialty and residency choices. The second survey, directed
      to 40 medical residency program directors in family medicine, internal medicine,
      pediatrics, and surgery, sought to identify the characteristics of applicants
      that these directors valued when selecting entrants to their programs. The third
      survey, of 30 employers of physicians representing four practice environments
      (private practice, hospitals/other health systems, academic medical centers, and
      health maintenance organizations), sought information on hiring and recruitment
      practices and the skills, competencies, and attitudes these employers valued most
      when hiring recently graduated physicians. The responses showed several
      differences and/or misperceptions among the views held by the three groups
      surveyed and suggest that medical educators have not adapted as rapidly as have
      employers to changes in the health care environment. Academic health centers must
      broaden their missions and make changes in their own institutional cultures, both
      to maintain their own viability and to train physicians who have the balance
      between scientific and technical competency and essential personal
      characteristics (such as empathy) that the next century's practice will probably
      demand.

PMID- 7718056
TI  - A strategy for selecting the best content for basic science courses.

PMID- 7718058
TI  - Linking excellence in teaching to departments' budgets.
AB  - It is time for the research and clinical practice communities, which dominate
      medical schools, to realize that the enhanced support of teaching is essential
      not only for students and society but also because these communities' successes
      hinge on how well their investigators and clinicians were taught. The need to
      learn more about the evaluation of teaching should not be a barrier to the
      productive use of current knowledge about it, which is sufficient for schools to
      improve the standing and effectiveness of teaching. A greater focus on teaching
      is even more urgent now because the disbursement of medical school funding is
      changing, and fewer funds are being allowed for the use of education. Also, other
      pressures, such as greater demands on faculty time for research and patient care
      activities and the tendency for research and clinical care to evolve into
      autonomously governed activities, are distracting faculty from teaching. To
      establish a superior ethos for education, the author proposes a new approach to
      faculty compensation and advancement, in which half of the available resources
      would be distributed according to departmental merit, which would link
      compensation to the performance of the faculty group composing a department.
      Performance in both research and teaching in all venues of medical work would be
      weighed equally. The dean's office would be responsible for making departmental
      merit awards, using advice and information from faculty, students, and
      administrative staff, and all decisions would be reviewed with each department
      chair.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718060
TI  - The kaleidoscope of general internist careers: a challenge for internal medicine
      training.
AB  - As internal medicine residency programs struggle to produce general internists in
      greater numbers and assure that they are adequately prepared for practice, it is
      imperative that the graduate medical education system have a clear picture of
      what competencies will be expected of those entering general internist careers.
      Feedback from the practicing community and large managed care organizations in
      Minnesota has made it clear that general internists in that state are functioning
      in a variety of positions requiring a wide range of skills depending on the
      practice description, choice of practice setting, and the complement of other
      primary care providers. General internists functioning in nontraditional careers
      have special curricular needs. It is imperative that training programs constantly
      monitor the changing practice environment and stay current on the variety of new
      generalist career choices to adequately prepare their residents for generalist
      careers. The graduate medical education enterprise needs to be involved in
      determining the best teaching strategies for the broad range of ambulatory
      general medicine competencies and in determining how best to preserve the
      richness of the medical subspecialty experience critical to the training of
      excellent general internists.

PMID- 7718059
TI  - Content validation of key features on a national examination of clinical decision
      making skills.
AB  - Key features (KFs) represent the critical, or essential, steps in the
      identification and management of a clinical problem. KFs for 59 clinical problems
      were defined by members of a test committee for the Medical Council of Canada as
      part of their efforts to create a more valid written examination of clinical
      decision-making skills for the Canadian Qualifying Examination in Medicine. In
      order to evaluate the content validity of KFs that the test committee had defined
      for the examination, 99 physicians from outside the committee, who came from
      clerkship programs at all 16 of Canada's medical schools, participated in three
      studies conducted in 1991. The first study was retrospective and was designed to
      find the degree of agreement or disagreement that the outside physicians had with
      the KFs already defined for each problem by the committee members. The second
      study was prospective and was to compare the KFs generated de novo by the
      participants with those already defined by the committee members. The third study
      was to gather the outside physicians' opinions of the frequencies with which
      graduating students in Canada are exposed to the 59 problems used in the
      retrospective and prospective studies. Almost all the KFs defined by the test
      committee were corroborated by the outside physicians, 92% in the retrospective
      study and 94% in the prospective one.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718061
TI  - The organization of the digital library.
AB  - As digital information proliferates and the difficulties of managing it threaten
      to overwhelm traditional publication and information delivery processes, new
      visions of a digital library are forming. Exactly what a digital library is and
      how it is to be organized have not yet been determined, and bibliographic
      organization of digital information has not been sufficiently addressed.
      Bibliography is the systematic description or classification of writings or
      publications considered as material objects. In today's digital world, such
      material objects may no longer be relevant, but the need for systematic
      description remains. The important issue is not whether digital bibliography is
      needed but, instead, whether or not existing bibliographic techniques are
      appropriate for this new media. A second issue is the location of the
      responsibility for a new digital bibliography. Does it rest with medical
      informaticians, often the producers of this new digital information, or with
      librarians, traditionally the classifiers of information? Developments in both
      medical informatics and medical librarianship indicate a need for greater
      collaboration between these specialties in order to achieve their common purpose-
      the creation, classification, and dissemination of scholarly information.

PMID- 7718062
TI  - Preparing for health care reform and an LCME site visit: addressing the
      generalist-non-generalist imbalance.
AB  - PURPOSE: The purpose of the present study was to evaluate primary care outcomes
      for the Loma Linda University School of Medicine (LLUSM), using Association of
      American Medical Colleges (AAMC) data files. The two principal objectives were to
      estimate the percentages of LLUSM graduates who are practicing or will practice
      primary care medicine and to determine what information available on application
      to LLUSM is useful in predicting graduates' specialty choices (i.e., primary
      versus non-primary care). METHOD: In 1993-94 data were taken from several AAMC
      data files (available to all medical schools), including the Graduate Medical
      Education (GME) Tracking Census and the American Medical College Application
      Service (AMCAS) Applicant Master File. The second and fourth years after
      graduation were used as points of evaluation. Primary care (generalist) was
      defined as taking or having completed a residency in family practice, internal
      medicine, or pediatrics, and not having taken any fellowship training. RESULTS:
      Fourth year after graduation: 42.4% of the 1,064 LLUSM graduates (1983 to 1990)
      were training in or had completed residencies in family practice (19.8%),
      internal medicine (16.2%), or pediatrics (6.4%). Second year of GME: of the 1,365
      LLUSM graduates (1983 to 1992), 49.3% were in the primary care pipeline (19.8% in
      family practice, 21.9% in internal medicine, and 7.6% in pediatrics). Two
      variables available on admission to medical school were associated with being in
      the primary care pipeline (second-year GME generalist): being a woman and being a
      member of a non-underrepresented minority. One variable was associated with being
      in the non-primary care pipeline: having a rural county code. Undergraduate
      grades and Medical College Admission Test scores were not good predictors.
      CONCLUSION: The AAMC data files, available to all medical schools, are useful for
      estimating and evaluating primary care outcomes.

PMID- 7718063
TI  - Gender comparisons of young physicians' perceptions of their medical education,
      professional life, and practice: a follow-up study of Jefferson Medical College
      graduates.
AB  - PURPOSE: To obtain information from a group of young physicians and compare men
      and women on their evaluations of selected areas of the medical school
      curriculum, their perceptions of issues related to medical practice and
      professional life, and their specialty choices, professional activities, and
      research productivity. METHOD: In 1992, a questionnaire was mailed to 1,076
      physicians who had graduated from Jefferson Medical College between 1982 and
      1986. The responses of men and women were compared using multivariate and
      univariate analyses of variance, t-tests, chi-square, and median test. RESULTS:
      Completed questionnaires were returned by 667 graduates (530 men and 137 women).
      The curriculum areas of interpersonal skills, disease prevention, medical ethics,
      and economics of health care were rated by both men and women as being the most
      important in medical training. Conversely, research methodology and statistics
      received the lowest ratings. Women, in general, valued psychosocial aspects of
      medical care higher than did men. Among the areas of perceived problems related
      to practice, lack of leisure time received the highest ratings (as being the
      greatest problem) and interpersonal interactions received the lowest ratings (as
      being the least problem) from both men and women. The men were more concerned
      than the women about the areas of patient chart and documentation, malpractice
      litigation, physician oversupply, peer review, and interaction with patients.
      These differences remained when specialties and numbers of hours worked per week
      were held constant. Generally, the physicians reported satisfaction with their
      professional lives, but the men tended to be more satisfied than the women about
      their decisions to become physicians and in their perceptions of medicine as a
      rewarding career. The proportion of men employed full-time (99.4%) was
      significantly higher than that for women (84%). Women were more likely to
      practice general pediatrics, while men were more likely to practice surgery and
      surgical subspecialties. Full-time--employed women worked fewer hours per week
      (57) than men (63), and men reported more research productivity than women.
      CONCLUSION: The implications of the findings of numerous gender differences are
      discussed regarding the issues of physician workforce, types of care rendered by
      men and women, and possible changes in the national health care system.

PMID- 7718065
TI  - Demographic, educational, and psychosocial factors influencing the choices of
      primary care and academic medical careers.
AB  - PURPOSE: To identify demographic, psychosocial, and educational variables that
      differentiate physicians who have chosen careers in primary care from those who
      have chosen academic medicine. METHOD: Questionnaires were distributed in the
      spring of 1992 to 704 physicians (546 in primary care practices and 143 in
      academic medicine) who had graduated from the University of Kentucky College of
      Medicine, 1964-1991. Mann-Whitney U tests and analyses of variance were used for
      statistical comparisons. RESULTS: A total of 336 physicians responded: 246 in
      primary care and 90 in academic medicine. The primary care physicians tended to
      come from smaller cities than did the academic physicians (p < .0001). The
      primary care physicians also had made their career choices earlier than did the
      academic physicians (p < .0001). For the academic physicians, long-term
      participation in research, intellectual stimulation, content of specialty, and
      influence of a mentor or role model were significantly more important factors
      than they were for the primary care physicians, for whom length of training,
      direct patient contact, and threats of malpractice suits were significantly more
      important. CONCLUSION: The results corroborate the findings of previous studies
      that suggest that career-choice factors are influenced by admission procedures
      and curricular structures. The number of graduates choosing careers in either
      primary care or academic medicine may be increased by increasing their
      experiences in those fields. Medical schools may be able to use demographic,
      psychosocial, and curricular factors to fulfill their particular primary
      mandates, whether they be producing physicians in primary care or in academic
      medicine.

PMID- 7718066
TI  - Effect of anonymous test grading on passing rates as related to gender and race.
AB  - BACKGROUND: Concerns about potential bias in the grading of medical students at
      the Southern Illinois University School of Medicine led to a major institutional
      policy change whereby students' identities were masked during the test-grading
      process. The present study assessed the effect of this anonymous test grading
      policy by comparing the performance of men and women students and of white and
      African American students prior to and after adoption of the policy change.
      METHOD: A test-passing rate was determined for each of 476 freshmen students in
      the comparison groups from the eight classes of 1988 through 1995. Mean test
      passing rates for the four student cohorts prior to policy implementation (1988
      1991) were compared with mean passing rates after the policy was implemented
      (1992-1995). RESULTS: The pre-post change in the mean test-passing rate of men
      was not significantly different from the pre-post change of women, and a
      nonsignificant effect was also found when the pre-post change in the mean test
      passing rate of white students was compared with that of African American
      students. No significant pre-post change was found for white men, white women,
      African American men, or African American women. CONCLUSION: The results showed
      no effect of the anonymous test-grading policy, which suggests that there was no
      widespread gender or racial bias in the grading of freshman medical students
      before the change in institutional grading policy.

PMID- 7718064
TI  - Comparing checklists and databases with physicians' ratings as measures of
      students' history and physical-examination skills.
AB  - PURPOSE: To compare two methods of rating students' performances on history and
      physical examination: (1) by using checklists completed by standardized patients
      (SPs) and databases completed by students, and (2) by using ratings of students
      by three physicians for each SP-student encounter. METHOD: Four cases were chosen
      for the study, and 30 students were examined per case. The students were all in
      their fourth year at the Southern Illinois University School of Medicine in the
      spring of 1991. Two of the cases had both checklists and databases, and the
      remaining two had databases only. Each SP-student encounter was videotaped and
      was viewed independently by three physicians unfamiliar with the contents of the
      checklists and databases. The physicians' pooled ratings were then compared with
      the checklist and database scores. Uncorrected and corrected correlations were
      obtained, with the generalizability coefficient used as the index of reliability.
      RESULTS: Interrater generalizability of physicians' ratings was very good,
      ranging from .65 to .93 for overall ratings. Generalizability of physicians'
      ratings pooled across the four cases was .85. Checklist scores tended to
      correlate higher with physicians' ratings than did database scores: across the
      cases, correlation coefficients between physicians' ratings and checklist scores
      and database scores were .65 and .39, respectively. CONCLUSION: The checklist
      scores correlated strongly with the physicians' ratings of history and physical
      examination skills, providing some evidence of validity for their use. The
      checklist scores correlated much better with the physicians' ratings than did the
      database scores. Possible explanations for this finding are discussed.

PMID- 7718067
TI  - Effect of student and preceptor gender on clinical grades in an ambulatory care
      clerkship.
AB  - BACKGROUND: Although several studies have addressed the effect of student gender
      on clinical performance evaluation, none has looked at the effect of preceptor
      gender or the interaction of preceptor gender and student gender. We investigated
      the possibility of gender effects in an ambulatory care clerkship where the
      preceptor-student ratio is usually one to one. METHOD: Clinical grades given by
      preceptors to third-year students after a required one-month ambulatory care
      medicine clerkship were analyzed by student gender, preceptor gender, and
      preceptor-student gender pairs. The study was conducted from August 1990 to
      October 1992 at the Medical College of Wisconsin. A total of 121 preceptors (97
      men and 24 women) and 375 students (233 men and 142 women) participated. Analyses
      of variance were used to detect significant differences. RESULTS: On a scale of 0
      to 4, the female students received a higher mean clinical grade than the male
      students (3.1 versus 3.0, p < .04). Preceptor gender had no effect on clinical
      grades until student gender was considered. The highest mean grade of 3.3 was
      given by male preceptors to female students, and the lowest mean grade of 2.9 was
      given by female preceptors to male students (p < .01). CONCLUSION: The female
      students received higher clinical grades in the ambulatory care clerkship,
      especially when the preceptor was male. Perhaps gender interaction should be
      considered when assigning students to preceptors and evaluating grading
      practices.

PMID- 7718068
TI  - The effect of pass/fail grading and weekly quizzes on first-year students'
      performances and satisfaction.
AB  - BACKGROUND: In 1992-93 the University of Michigan Medical School revised its
      first-year curriculum. An evaluation system using honors, high-pass, pass, and
      fail grading and only two examinations (a midterm and a final) was replaced with
      a system using pass/fail grading and weekly quizzes in addition to the two
      examinations. The objective was to increase students' satisfaction while
      maintaining a high level of achievement. METHOD: Students' performance scores and
      survey data from the final year of the former system (1991-92, 222 students) and
      the first year of the new system (1992-93, 195 students) were used to investigate
      whether overall performance decreased and whether the students liked the new
      approach to grading. Statistical methods used were one-sample t-tests, Student's
      t-test, and Fisher's Z-test. RESULTS: Under the new system, the average scores
      for courses remained well above passing, and no evidence was found that the
      students achieved at lower levels than had their predecessors with the former,
      more traditional grading system. Also, higher cumulative pre-final scores (i.e.,
      scores on the weekly quizzes as well as the midterm) did not predict lower, "just
      passing" achievement on final examinations. The students' responses to the
      surveys included comments that pass/fail grading eased anxiety and reduced
      competition while encouraging the students' co-operation. CONCLUSION: Despite
      concerns that implementing pass/fail grading for all first-year courses would
      result in lower overall performance and decreased motivation among students,
      during the first year of implementation these fears proved to be unfounded as the
      students continued to perform well and reported greater satisfaction with the new
      system.

PMID- 7718069
TI  - The decline and rise of the medical school applicant pool.
AB  - The authors characterize the demographic changes that transpired with the decline
      and rise of the medical school applicant pool over the past decade, and describe
      the variations in academic antecedents, attrition, and graduation rates of
      students matriculated during that time. Data over the ten-year cycle, derived
      from the AAMC's Student and Applicant Information Management System (SAIMS), were
      examined in the context of published education and employment statistics. The
      contraction and expansion of the applicant pool were related to changes in the
      number and pattern of undergraduate majors and to changes in the employment
      conditions for college-educated youth. Furthermore, a significant part of the
      variations in size of the applicant pool is an artifact of changes in the number
      of repeat applications. Matriculants' pre-medical grades and MCAT scores dropped
      slightly during the period of applicant decline, and rebounded as admission
      committees were able to exercise greater selection when the pool expanded. The
      attrition of medical students rose and fell during this time, but the changes
      were small and of little discrete influence on graduation rates during the
      period. The downturn and rebound in applications over the past decade appear to
      be more related to cycles in the employment market for college graduates than to
      applicants' perceptions of unfavorable/favorable conditions in medical education
      and practice.

PMID- 7718072
TI  - The Harstad Injury Prevention Study: evaluation of hospital-based injury
      recording and community-based intervention for traffic injury prevention.
AB  - In a quasi-experimental study, hospital-treated traffic accident injuries were
      recorded prospectively for 7 1/2 years in the two Norwegian cities, Harstad and
      Trondheim. In Harstad the recorded data were used actively in analysis, planning,
      and implementation of a community-based injury prevention program. Trondheim was
      the nonequivalent control city. The intervention was divided into three periods,
      each of 30 months duration. Preventive efforts were implemented to some extent in
      period 1, increasingly in period 2 and period 3. Traffic safety was promoted in
      an extensive community program based on the Ottawa charter for health promotion.
      A 26.6% overall reduction of traffic injury rates was found in Harstad from
      period 1 to period 3 (p < 0.01), whereas a corresponding significant increase was
      found in the comparison city. Analysis of data from other sources were not
      conclusive in supporting the Trondheim data as showing the national trend.
      Alternative explanations for the injury rate reduction in Harstad were assessed
      by means of other available relevant data. The exact mechanisms that brought
      about the reduction of injury rates were hard to elucidate because so many
      intervention elements were implemented at the same time. It is concluded that at
      least some of the reduction was due to behavioural and structural changes brought
      about by health promotion. Important factors for the effect of and participation
      in the prevention program were local relevance and continuous feedback of
      accident injury data.

PMID- 7718071
TI  - Injury severity of restrained front seat occupants in car-to-car side impacts.
AB  - The influence of a number of factors, including age and particularly seating
      position, on the injury severity of restrained occupants was examined for 41
      front-seat occupants seated adjacent to the impact (near side) and 38 sitting
      opposite the impacted side (far side) in car-to-car side collisions (center of
      impact: front door and B-pillar). Above an energy equivalent speed of 40 km/h all
      near-side occupants and about half of the far-side occupants sustained severe
      injuries. A logistic regression analysis showed that within range of 30-60 km/h
      (delta v 20-60 km/h) the probability of severe injuries increased dramatically
      from approximately 20% to more than 90%; in these cases, far-side occupants had
      the same injury probability as near-side occupants only when the speed was 10
      km/h higher. The main cause of death for 27 occupants seated on both sides was
      polytrauma, this was accompanied in two-thirds of the cases by serious head
      injuries. The second most frequent cause of death was head injury.

PMID- 7718070
TI  - Measuring the contribution of randomness, exposure, weather, and daylight to the
      variation in road accident counts.
AB  - Road accident counts are influenced by random variation as well as by various
      systematic, causal factors. To study these issues, a four-country, segmented data
      base has been compiled, each segment consisting of monthly accident counts, along
      with candidate explanatory factors, in the various counties (provinces) of
      Denmark, Finland, Norway, or Sweden. Using a generalized Poisson regression
      model, we are able to decompose the variation in accident counts into parts
      attributable to randomness, exposure, weather, daylight, or changing reporting
      routines and speed limits. To this purpose, a set of specialized goodness-of-fit
      measures have been developed, taking explicit account of the inevitable amount of
      random variation that would be present in any set of accident counts, no matter
      how well known the accident generating Poisson process. Pure randomness is seen
      to "explain" a major part of the variation in smaller accident counts (e.g. fatal
      accidents per county per month), while exposure is the dominant systematic
      determinant. The relationship between exposure and injury accidents appears to be
      almost proportional, while it is less than proportional in the case of fatal
      accidents or death victims. Together, randomness and exposure account for 80% to
      90% of the observable variation in our data sets. A surprisingly large share of
      the variation in road casualty counts is thus explicable in terms of factors not
      ordinarily within the realm of traffic safety policy. In view of this
      observation, it may seem unlikely that very substantial reductions in the
      accident toll can be achieved without a decrease in the one most important
      systematic determinant: the traffic volume.

PMID- 7718073
TI  - Who carries passengers in the back of pickup trucks?
AB  - This study was designed to compare pickup truck drivers who carried passengers in
      the back with those who did not, with respect to driving behaviors,
      sociodemographic features, and issues related to use of the pickup truck. A
      computerized assisted telephone survey was conducted in Riverside County,
      California. One thousand ten motor vehicle drivers were interviewed with respect
      to demographics, restraint use, driving behaviors, and variables related to
      vehicle use. Thirty-six percent (364) of the households had a pickup truck
      driver. Pickup drivers were grouped into those who stated that they had carried
      occupants in the back (n = 119) and those who had not (n = 245). A higher
      proportion of 16- to 24-year-old and 35- to 44-year-old pickup truck drivers
      carried passengers in the back of pickup trucks. Those who carried occupants in
      the back were significantly more likely to be Hispanic, to be students, and to
      live in a household that included teenagers. They also had a larger mean
      household size. They were less likely to own the pickup and less likely to be the
      principal wage earners. They were more likely to report four high-risk driving
      behaviors. They also used the pickup truck for multiple purposes, i.e.
      recreation, work, school transportation, and daily transportation. In the
      multivariate analysis, the presence of teenagers in the household, three high
      risk driving behaviors, and three indicators of pickup truck use were
      independently related to carrying passengers in the back of a pickup. Those who
      allowed passengers in the back were significantly less likely to agree with
      statements suggesting restriction of travel in the back. Finally, only 9% of the
      respondents who carried passengers in the back of a pickup reported that the
      pickup truck was the only vehicle available in the household.

PMID- 7718074
TI  - Marijuana and other drug use among automobile and motorcycle drivers treated at a
      trauma center.
AB  - Serum from injured automobile and motorcycle drivers treated at a trauma center
      was tested for delta-9-tetrahydrocannabinol activity to determine precrash
      marijuana use. From June 1990 to March 1991, samples from approximately 20
      automobile drivers per month and all motorcycle drivers were available for
      testing. Also, toxicology screens were performed for ethyl alcohol, cocaine, and
      phencyclidine (PCP) among the driver groups. Six (2.7%) of the 225 automobile
      (AUT) drivers and 34 (32.0%) of the 106 motorcycle (MTC) drivers were THC+ (p <
      .001). Compared with a prior study, the THC+ rate decreased significantly from
      31.8% among AUT drivers (p < .001) but had not changed significantly from the
      38.6% rate among MTC drivers. Positive toxicology rates were higher among the 261
      MTC drivers compared to the 1,077 AUT drivers tested for ETOH, CO, and PCP, being
      47.1% vs 35.2% (p < .001), 5.0% vs 8.0% (p < .08), and 1.5% vs 3.1% (NS),
      respectively.

PMID- 7718075
TI  - Statistical analysis of motorcyclists' perceived accident risk.
AB  - Motorcycling is generally recognized as a relatively risky activity, but
      surprisingly little is known about motorcyclists' perception of this risk. This
      paper presents a survey of motorcyclists' perceived likelihood of being involved
      in an accident and a statistical analysis of the factors determining this
      likelihood. Our results show that motorcyclists have a reasonable grasp of the
      factors that increase the likelihood of accident involvement. These factors
      include exposure (miles ridden), regularly riding above the speed limit, and
      passing vehicles on the shoulder or passing between lanes of traffic. The
      findings suggest that motorcycle accidents are, for the most part, not the result
      of misjudgments about the overall risk of motorcycling.

PMID- 7718076
TI  - Schedule-induced hours-of-service and speed limit violations among tractor
      trailer drivers.
AB  - Driver fatigue is well recognized as an important causational factor in accidents
      involving long-distance truck drivers. Drivers may drive while fatigued for a
      variety of reasons. Important among these is the assignment of difficult or
      unreasonable delivery schedules. Using self-reported data, the frequency of
      violation-inducing schedules is estimated during their ongoing movement for a
      sample of 498 long-distance drivers. Assuming average legal speed limits of 55
      MPH, 26% of the drivers were found to have violation-inducing schedules. Solo
      drivers, drivers hauling refrigerated loads, regular route drivers, and those
      with longer current trip distances are the most likely to have such schedules.
      Also estimated were total weekly work hours. Assuming average attained travelling
      speeds of 50 MPH, the average driver drives 46 hours per week and works a total
      of 58 hours.

PMID- 7718077
TI  - Bicycle helmet use patterns in the United States. A description and analysis of
      national survey data.
AB  - While there have been considerable efforts to promote bicycle helmet use in the
      United States in recent years, little information has been available on actual
      helmet usage patterns. Based on the results of a recent national survey, this
      article provides information on current helmet usage patterns, the types of
      helmets in use, and the reasons why bicycle riders use or do not use helmets. It
      also presents a statistical analysis of the factors associated with helmet use.
      These factors are determined and quantified with a probit regression model, a
      type of qualitative response model that can be used to estimate the expected
      probabilities of helmet use for individual bicyclists and for various population
      subgroups. The regression analysis shows that helmet use is systematically
      related to riding patterns, rider characteristics, and household demographics.

PMID- 7718078
TI  - Effects of a video warning sign and social modeling on behavioral compliance.
AB  - Two experiments were conducted to evaluate the effectiveness of different kinds
      of video presentations as methods to induce behavioral compliance to safety
      directives. In Experiment 1, the effects of: (i) a video sign warning alone, (ii)
      a video sign warning plus a role model, and (iii) a video sign warning plus a
      role model with an added voice warning were examined with respect to compliance
      with directed safety behaviors. The results indicated that behavioral compliance
      was significantly higher when participants were exposed to the videos containing
      the role model compared to the video sign alone. The addition of a voice warning
      to the sign plus role model condition produced no further increase in compliance
      over the condition without voice. Experiment 2 examined whether a delay between
      the time of exposure to the video and the time the safety behaviors were
      necessary would produce a decrease in compliance. In addition, the influence of a
      video role model and a voice warning on perceived importance of protective
      equipment was examined. Experiment 2 showed that a delay of several days did not
      reduce the effectiveness of a video warning. This result suggests that the
      behavioral change induced by the video is robust over time. In addition, a
      significant relationship between perceived importance of using safety equipment
      and behavioral compliance was demonstrated. Implications of this research for
      safety training programs and warnings are discussed.

PMID- 7718079
TI  - Drinking and driving of pub patrons in Israel.
AB  - A chance sample of people exiting pubs in Israel were interviewed and their blood
      alcohol concentration (BAC) was measured with a portable breathalizer.
      Approximately 50% of the people intended to drive away themselves, while 50% were
      driven by others. People's decision whether or not to drive was unrelated to
      their BAC and to the number of drinks they reportedly had, and only marginally
      related to whether or not they felt drunk. Thirty percent of those who felt drunk
      still intended to drive. Although three-quarters of the respondents felt there is
      a driving and drinking problem in Israel, their knowledge about the effects of
      alcohol and the number of drinks they need to consume in order to get drunk
      reflected an alarming ignorance. The results demonstrate a dangerous trend in
      alcohol consumption that is not coupled with adequate specific knowledge about
      alcohol's effects.

PMID- 7718080
TI  - Traffic accident involvement rates by driver age and gender.
AB  - Passenger-vehicle travel data from the 1990 Nationwide Personal Transportation
      Survey were combined with crash data from the 1990 Fatal Accident Reporting
      System and the 1990 General Estimates System to produce crash involvement rates
      per vehicle-mile of travel. Elevated rates were observed for drivers aged 16-19
      and 75 and over. The oldest drivers had the highest fatal involvement rate, while
      the youngest drivers had the highest rate of involvement in all police-reported
      crashes. Men had a higher risk than women of experiencing a fatal crash, while
      women had higher rates of involvement in injury crashes and all police-reported
      crashes.

PMID- 7718081
TI  - An examination of the crash involvement rates of novice drivers aged 16 to 55.
AB  - There is general agreement in the literature that both age and driving experience
      correlate with aggregated accident risk for driver populations. The very young
      and beginning drivers have been classified as groups that are overrepresented in
      crashes, but unfortunately the former is often used as a surrogate for
      conclusions concerning the latter. The research that we undertook examined the
      interactions of various driving exposure and accident characteristics with both
      culpable and nonculpable crash involvements for 149,000 British Columbia novice
      drivers between the ages of 16 and 55. In assessing the results of our enquiry we
      were unable to substantiate that any of the supposed "risky" driving situations
      often proposed for graduated licencing system exposure restrictions (such as
      nighttime curfews, no highway driving, etc.) more adversely affected drivers in
      their first as compared to subsequent two years of driving, even though some
      (such as alcohol presence) were significantly correlated with accident fault
      assessment. The results did, however, suggest that licence restrictions or some
      other form of sanction applied following initial traffic law contraventions could
      address a substantial proportion of subsequent crash involvement likelihood. When
      considering only young novices (aged 16 to 18 years), the results were not
      greatly different, although for these drivers the carrying of passengers was
      found to be significantly more associated with first-year crashes than with those
      in subsequent years.

PMID- 7718082
TI  - Dendritic cells as initiators of tumor immune responses: a possible strategy for
      tumor immunotherapy?

PMID- 7718083
TI  - Tolerance induction in the adult: 'danger' at Le Bischenberg.

PMID- 7718084
TI  - Serum HLA class I antigens: markers and modulators of an immune response?

PMID- 7718085
TI  - Can live attenuated virus work as post-exposure treatment?
AB  - Simple mathematical models for the competition between different virus variants
      in the presence of a crossreactive immune response show that, contrary to
      expectation, selection can favour variants that induce low viral loads. Here,
      Sebastian Bonhoeffer and Martin Nowak suggest that such 'competitively superior',
      but 'less pathogenic', mutants may be a possibility for post-exposure treatment
      of persistent virus infections.

PMID- 7718086
TI  - Physiological enzymatic cleavage of leukocyte membrane molecules.
AB  - Certain membrane molecules are enzymatically cleaved from the cell surface and
      then released into the extracellular medium in the form of soluble fragments.
      This process, commonly initiated by cell stimulation, may regulate the surface
      expression of such molecules, and may also be responsible for the production of
      their soluble forms in vivo. Here, Vladimir Bazil provides an overview of the
      molecules that are cleaved from cells, focusing particularly on leukocyte
      receptors. In addition, he discusses the mechanisms and putative enzymes involved
      in this process, as well as the potential physiological significance of such
      events.

PMID- 7718087
TI  - The proportion of B-cell subsets expressing kappa and lambda light chains changes
      following antigenic selection.
AB  - Using a mixture of 'top-down' theory and 'bottom-up' extrapolation from
      experimental observation, Rodney Langman and Melvin Cohn discuss some of the
      conflicting points of view regarding the ratio of kappa (kappa)- to lambda
      (lambda)-expressing B cells. Despite the somewhat arcane nature of the subject,
      the authors make a strong general case for the use of computer simulations as a
      means of reconciling top-down generalizations with quantitative bottom-up
      extrapolations. With the appearance of two recent papers, the authors show how
      the top-down theory prevailed in a resolution of the controversy.

PMID- 7718088
TI  - Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal
      superantigens?
AB  - Psoriasis is a T-cell-mediated disease that can be triggered by infection with
      group A beta-haemolytic streptococci. It is proposed that psoriatic skin lesions
      are initiated by exotoxin-activated T cells, and persist because of specific T
      cells that react both with streptococcal M protein and a skin determinant,
      possibly a variant of keratin. As discussed here by Helgi Valdimarsson and
      colleagues, cytokines released by the superantigen (SAg)-stimulated T cells could
      induce or enhance the expression of the crossreactive autoantigen, leading to the
      rescue and activation of autoreactive T cells. In this way, the SAg-determined T
      cell receptor V beta phenotype would be maintained by T cells in psoriatic
      lesions.

PMID- 7718089
TI  - The basis of autoimmunity: Part II. Genetic predisposition.
AB  - In Part II of his review of the basis of autoimmunity, Argyrios N. Theofilopoulos
      summarizes current knowledge on the genetic factors that contribute to autoimmune
      disease predisposition. The findings indicate that multiple genes contribute to
      the induction of pathogenic autoimmunity, and that no single genetic abnormality
      is sufficient in itself to induce disease. The definition of these genetically
      complex diseases is about to be revolutionized by the development of genome
      scanning approaches, such as dense chromosomal maps based on polymorphic
      microsatellite DNA and other informative markers. These will allow the loci and
      genes that predispose to these diseases to be identified broadly.

PMID- 7718090
TI  - The regulation and function of p21ras during T-cell activation and growth.
AB  - The delivery of signals that control the growth of T cells is a key event for
      effective co-ordination of T-cell-dependent immune responses. It is now
      recognized that guanine nucleotide binding proteins play an important role in
      signal transduction by the T-cell receptor (TCR) and cytokine receptors. Here,
      Manolo Izquierdo Pastor, Karin Reif and Doreen Cantrell review the numerous
      recent advances in understanding how the p21ras guanine nucleotide binding
      protein couples the TCR to the T-cell signalling cascade.

PMID- 7718091
TI  - Psychological aspects of stress immunology.

PMID- 7718092
TI  - Immunotherapy for recurrent miscarriage. Consensus conference. Washington, D.C.,
      July 16-17, 1993.

PMID- 7718093
TI  - Immunotherapy for recurrent miscarriage.

PMID- 7718094
TI  - Immunotherapy with intravenous immunoglobulin for prevention of recurrent
      pregnancy loss: European experience.
AB  - PROBLEM: Due to its strong "immunomodulating" effect in several well established
      disorders, high-dose intravenous immunoglobulins (IVIG) has been proposed as an
      alternative for immunotherapy with allogeneic leucocytes in patients with
      unexplained recurrent spontaneous abortion. This paper is intended to provide an
      overview on the European experience in this field. METHOD: Five European pilot
      studies with a total of 172 patients as well as one controlled double-blind
      multicenter study including 64 patients were considered. In the latter, 5% human
      albumin was used as placebo. RESULTS: Success rates of the pilot studies varied
      from 68 to 87%. In the German controlled study, a significant specific effect of
      IVIG could not be verified. However, success rates for both IVIG and albumin were
      in the same range as for allogeneic leucocytes. CONCLUSION: At present, it is not
      sufficiently proven that IVIG is an appropriate tool for immunotherapy of
      recurrent spontaneous abortions. It is suggested that success rates of both IVIG
      and albumin are due to a placebo effect. However, we cannot exclude that albumin
      itself provides immunomodulating capacity.

PMID- 7718095
TI  - Immunotherapy with intravenous immunoglobulin for treatment of recurrent
      pregnancy loss: American experience.
AB  - PROBLEM: Recurrent spontaneous abortion (RSA) is the cause of childlessness in 2
      5% of reproducing couples. Immunological mechanisms have been proposed as an
      etiology in some cases of RSA. Various forms of immunotherapy have been attempted
      in individuals thought to have an immunologic mechanism associated with RSA.
      Intravenous immunoglobulin (IVIG) has been used in a pilot study to successfully
      treat women with RSA. METHOD: To evaluate the efficacy of IVIG in the prevention
      of RSA as prospective randomized, placebo-controlled clinical trial was
      undertaken. Women experiencing two or more consecutive RSAs receive either IVIG
      500 mg/kg/month or placebo (albumin). RESULTS: To date 92 women have been
      enrolled in the study and 58 pregnancies have been achieved. The outcome of the
      58 pregnancies include 20 deliveries, 9 ongoing pregnancies and 29 losses.
      Fourteen (49%) of the 29 pregnancy losses were blighted ova (empty gestational
      sacs) and 15 (51%) were intrauterine fetal deaths (IUFD's) occurring in the first
      trimester of pregnancy. Of 14 blighted ova, 8 were in women receiving IVIG and 6
      were receiving placebo. Fifteen IUFD's occurred: 3 (20%) in women receiving IVIG
      and 12 (80%) placebo. Of 11 pregnancy losses occurring in women receiving IVIG, 8
      (73%) were blighted ova and 3 (27%) were IUFD's. Eighteen losses occurred in
      women receiving placebo: 6 (33%) were blighted ova and 12 (67%) were IUFD's.
      CONCLUSIONS: These preliminary data suggest IVIG may be effective treatment for
      RSA. Analysis of data from the completed randomized placebo-controlled trial will
      test this suggestion.

PMID- 7718096
TI  - Intralipid as treatment for recurrent unexplained abortion?
AB  - PROBLEM: Safe, effective, and inexpensive alternatives to partner leukocyte
      immunotherapy are being sought. Psychotherapy may be effective but it is
      uncertain what constitutes effective treatment and the form of treatment tested
      in cohort controlled trials is expensive. IVIG also appears effective, but is
      expensive. METHOD: A published double blind randomized controlled trial in which
      Intralipid (Kabi Vitrum, Toronto, Ontario) was used as a control versus
      trophoblast membrane vesicles was reviewed. A prediction made from this data was
      then tested using the DBA/2-mated CBA/J mouse model of recurrent spontaneous
      abortion. RESULTS: It can be hypothesized from the human clinical trial data that
      Intralipid even in small doses could be an effective antiabortion treatment. The
      number of patients in the published study is too small for the required degree of
      precision. Intralipid was highly effective in preventing abortion in mice, and
      protection was prolonged. This may be explained by previous data in the
      literature showing that Intralipid affects the reticuloendothelial system of the
      recipient. CONCLUSIONS: The evidence suggests that Intralipid might be an
      effective treatment for human recurrent miscarriages, and injection into women
      who may become pregnant has been found ethically acceptable at one university
      center. Comparison of Intralipid to partner leukocyte immunotherapy or IVIG would
      be worthwhile. For adequate statistical power, this would require a large,
      multicenter, prognostically stratified randomized controlled trial and could be
      accomplished via the Recurrent Miscarriage Immunotherapy Trialists Group network.

PMID- 7718097
TI  - The effectiveness of allogeneic leukocyte immunization in unexplained primary
      recurrent spontaneous abortion. Recurrent Miscarriage Immunotherapy Trialists
      Group.
AB  - PROBLEM: Unexplained primary recurrent spontaneous abortion (RSA) can be viewed
      as a partner-specific problem for which immunization with allogeneic leukocytes
      is being offered as therapy. Published data from randomized controlled trials
      have produced conflicting results regarding treatment effectiveness. The aim of
      this study was to perform a subgroup analysis of the data from a recent worldwide
      collaborative meta-analysis using the raw data for patients with primary RSA
      entered into randomized controlled trials of immunotherapy. METHODS: Data from
      randomized controlled trials in eight centers were included in this analysis.
      Individual patients were included only if they had had three or more spontaneous
      abortions, no previous pregnancy beyond 20 weeks' gestation, no identifiable
      cause for the abortions, and no evidence of antipaternal antibodies. Meta
      analysis by centre and logistic regression analysis were performed to determine
      the overall effect of treatment in achieving live birth and to identify variables
      that affect the prognosis for a successful outcome. RESULTS: In the meta-analysis
      by center, immunotherapy significantly improved the live birth rate (common odds
      ratio = 1.94, 95% confidence interval (CI) = 1.20 to 3.12). In the analysis by
      patient, the likelihood of a successful outcome was also significantly better
      with treatment (relative risk = 1.46, 95% CI 1.19 to 1.69). The absolute
      treatment effect was 16.3% producing a number needed to treat of 6. The number of
      previous abortions had a significant negative correlation with live birth rate,
      such that for each additional pregnancy loss beyond three, the likelihood of live
      birth was reduced by 23%. CONCLUSION: Allogeneic leukocyte immunization is an
      effective treatment for unexplained primary RSA when pretreatment antipaternal
      antibodies are absent. Better diagnostic tests are required to identify patients
      who may derive maximal benefit from this therapeutic approach.

PMID- 7718098
TI  - Fostering collegial relationships among lactation consultants.

PMID- 7718099
TI  - Join the LACTNET!

PMID- 7718100
TI  - Breastfeeding practices in Chengdu, Sichuan, China.
AB  - Barriers to increased breastfeeding rates in Chengdu, Sichuan were investigated
      in 1992 and 1993. Responses of focus groups showed that ignorance about
      breastfeeding and belief that the mother's milk was inadequate, and lack of
      support from their families, places of employment, and the health system acted as
      barriers to the women's breastfeeding their infants up to the age of four to six
      months. Subsequently, 363 mothers of 4- to 12-month-old Chengdu infants were
      surveyed. Although most mothers in both studies said breastmilk was the best food
      for their infant up to age of four to six months, only about half of the mothers
      breastfed for longer than one month. Both studies showed that infants who roomed
      with their mothers after birth were more likely to have been put to their
      mother's breast earlier, fed colostrum, breastfed somewhat longer, and
      exclusively breastfed for a somewhat longer period, although their mothers'
      infant feeding knowledge did not differ. The researchers conclude that Chengdu
      health workers should teach parents and parents-to-be more about breastfeeding,
      and that rooming-in be expanded in Chengdu hospitals.

PMID- 7718101
TI  - A comparison of chilled cabbage leaves and chilled gelpaks in reducing breast
      engorgement.
AB  - This study compared the effectiveness of chilled green cabbage leaves and chilled
      gelpaks in reducing breast engorgement in postpartum mothers. Thirty-four
      lactating women with breast engorgement used chilled cabbage leaves on one breast
      and chilled gelpaks on the other for up to eight hours. Their pain levels were
      established pre-treatment and compared post-treatment for both conditions. There
      was no difference in the post-treatment ratings for the two treatments. Mothers
      reported a statistically significant drop in pain with both treatments; 68
      percent obtained relief within one to two hours. The majority of mothers
      preferred the cabbage leaves.

PMID- 7718102
TI  - Infant demand and milk supply. Part 1: Infant demand and milk production in
      lactating women.
AB  - This first part of a two-part commentary examines evidence for the notion that
      human milk production is at least in part controlled by the infant's appetite.
      The studies that we review, of milk production by breastfeeding and expressing
      mothers, strongly support this hypothesis. Therefore, in established lactation
      and with a demand feeding regime, a mother's milk production is likely to be a
      reflection of her infant's appetite, rather than her ability to produce milk,
      which may in fact be several-fold higher. However, previous studies of human milk
      production have not provided a clear insight into how the lactating breast
      matches milk production to infant demand.

PMID- 7718103
TI  - Infant demand and milk supply. Part 2: The short-term control of milk synthesis
      in lactating women.
AB  - In this second part of our two-part commentary, milk production and milk
      synthesis are defined and the methods that may be used in their measurement are
      briefly reviewed. In particular, the rationale for the development of breast
      volume measurement techniques is described. We review our studies which have
      employed breast volume measurement techniques and propose a model for the short
      term control of milk synthesis in lactating women. According to this model, the
      breast responds to the degree to which the infant empties the breast at each
      breastfeed. The frequency of milk removal may not directly affect the rate of
      milk synthesis except as a function of the mother's ability to store milk.

PMID- 7718104
TI  - Increasing your credibility with physicians: strategies for lactation
      consultants.

PMID- 7718105
TI  - Narcotic analgesics and breastfeeding.

PMID- 7718106
TI  - Use of donor milk in the treatment of metabolic disorders: glycolytic pathway
      defects.

PMID- 7718107
TI  - Time was ... 1910. Nursing attachment.

PMID- 7718108
TI  - Positive media coverage of breastfeeding.

PMID- 7718109
TI  - Digest and discussion of the statistical report of the 1994 IBLCE examination.
      International Board of Lactation Consultant Examiners.

PMID- 7718110
TI  - President's column: ILCA's new standards of practice for LCs.

PMID- 7718111
TI  - An investigation into the mechanisms by which human dermis does not significantly
      contribute to the rejection of allo-skin grafts.
AB  - The dermis is an important element in skin substitutes and in allo- or xeno-skin
      grafts. However, the reason(s) why dermis does not significantly induce the
      immune rejection reaction in vivo remain(s) hitherto unknown. To clarify the
      mechanisms underlying this phenomenon, we undertook the evaluation of: (i) the
      response of the peripheral blood mononuclear cells (PBM) to isolated allo-dermal
      cells or to pieces of or to whole allo-dermis, (ii) the migration and homing of
      the PBM inside allo-dermis or split thickness allo-skin, (iii) the distribution
      of the ICAM-1 protein within skin, and (iv) the features expressed by the PBM
      that migrate into allo-skin. The results herein presented show that (1) the
      isolated allo-dermal cells had the highest and the whole allo-dermis the lowest
      capacity to initiate the reactive proliferation of the PBM in vitro; (2) in an
      allo-skin/PBM co-culture model, most of the PBM slowly, yet preferentially,
      migrated to and homed inside the allo-epidermal compartment, instead of staying
      in the allo-dermis; (3) under the conditions employed, rather little ICAM-1 could
      be immunohistochemically detected within the epidermis, conversely, both the
      dermal cells and the dermal matrix were ICAM-1 positive; and (4) most of the PBM
      migrating into the allo-skin pieces expressed either the CD18 or the CD19 or the
      CD8 molecule, yet very few of them exhibited the LFA-1-antigen, and none of them
      were found to be CD4 positive.2+Therefore, we conclude that because

PMID- 7718112
TI  - Evaluation of early enteral feeding in children less than 3 years old with
      smaller burns (8-25 per cent TBSA).
AB  - Early enteral feeding and high protein nutrition have been advocated for burned
      patients. The safety and efficacy of early high protein nasogastric feeding (NG)
      have not been evaluated in very young children. The present study evaluated such
      feeding in children less than 3 years old with smaller burns (8-25 per cent of
      total body surface area). Children (n = 10) were able to tolerate high protein
      intake without detrimental effects. The incidences of gastrointestinal
      complications related to NG feeding were low. The children needed approximately 2
      weeks of supplemental NG feeding which provided two-thirds of total energy intake
      and three-fourths of protein intake. In spite of smaller burns, the mean measured
      resting metabolic expenditure (REE) was 1.3 x predicted REE. The mean energy
      intake of 92 per cent of recommended daily allowances (RDA) for energy or 1.7 x
      predicted REE was able to maintain body weight. The mean protein intake was 4.3
      g/kg/day with a non-protein calorie ratio of 114:1. During the first week
      postburn, plasma concentrations of prealbumin, albumin and transferrin were low.
      The high protein intake was able to raise these visceral proteins to normal
      ranges. These results indicate that early NG feeding is safe and efficacious for
      achieving increased energy intake and improved protein status in very young
      children.

PMID- 7718113
TI  - Childhood burns in Ghana: epidemiological characteristics and home-based
      treatment.
AB  - The objectives of this research were to study the epidemiological characteristics
      and home-based treatment of childhood burns in the Ashanti Region of Ghana.
      Children aged 0-5 years with a burn history were identified through a community
      based, multisite survey. A standard questionnaire was administered to mothers of
      630 of these children to elicit information on their sociodemographic
      characteristics and the circumstances of the burn event. Ninety-two per cent of
      the burns occurred in the home, particularly in the kitchen (51 per cent) and the
      house yard (36 per cent), with most of them happening in the late morning and
      around the evening meal. The main causes of the burns were scalds (45 per cent),
      contact with a hot object (34 per cent) and flame (20 per cent). 'Cool' water was
      applied to the burned area in 30 per cent of cases. Otherwise, treatment with a
      traditional preparation was the most popular first-aid choice. Since a
      considerable proportion of burns happened between meals when children 'play with
      fire' in the house yard, the provision of alternative play activities and
      community play areas may reduce the incidence of burns to these children.
      Secondly, we recommend that education on first-aid management of burns be
      intensified, with special emphasis on alternatives to the use of traditional
      preparations.

PMID- 7718114
TI  - A preliminary exploration of the relationship between tumour necrosis factor
      (TNF) and monocytic in vitro production of interleukin-1 (IL-1) and internal
      organ dysfunction in severely burned patients.
AB  - Biological assays were adopted in this study to examine the changes in serum
      tumour necrosis factor (TNF) activity and blood monocytic in vitro production of
      interleukin 1 (IL-1) in 24 severely burned patients. The myocardial and hepatic
      enzymes (which included aspartate aminotransferase (AST), creatine kinase (CPK),
      lactate dehydrogenase (LDH), alpha hydroxybutyric dehydrogenase (alpha-HBDH) and
      alanine amino-transferase (ALT) and some indices of biochemical metabolism
      (including lactic acid (LA), total protein (TP), albumin (Alb) and colloid
      osmotic pressure (COP)) were simultaneously measured. The results showed an
      evident increase in serum TNF activity and a decrease in in vitro production of
      IL-1 postburn; all the changes in TNF and IL-1 were correlated significantly with
      those of myocardial and hepatic enzymes in MOF patients. Furthermore, there were
      marked fever, hypoproteinaemia, tissue ischaemic and hypoxic symptoms such as
      hyperlacticaemia, and signs reflecting tissue hypercatabolic states. These all
      suggested that TNF and IL-1 might play important roles in the development of MOF.

PMID- 7718115
TI  - Analysis of bacteriuria in patients with burns.
AB  - A detailed analysis of bacteriuria in 148 aged patients with burns was made for a
      period of 2 years (1991-92), in order to determine the incidence of the urine
      infections they sustained, the sources and mechanisms of the infections and the
      impact on the course and outcome of the primary disease. Urine infection was
      found in 7.6 per cent (46 patients) of all patients treated for burns during the
      study period; 39.1 per cent were community acquired uroinfection (CAU) and 60.9
      per cent were hospital acquired (HAU). In addition there were eight patients with
      bacteriuria, secondary to a generalized bacterial infection (GBI), and 11 with
      candiduria associated with massive antibacterial therapy. Leading causes of CAU
      were the common uropathogens: E. coli, Citrobacter and Proteus sp.; those of HAU
      were multiresistant hospital strains, characteristic of the Burns Clinic: Pseud.
      aeruginosa, Klebsiella sp., Acinetobacter sp. and Serratia sp. This study
      confirmed the role of transurethral catheterizations as factors associated with
      the development or exacerbation of chronic uroinfections, which increased the
      chances of non-survival, especially in aged people with concomitant chronic
      urological, nephrological or other underlying diseases. The causes of death in 20
      patients with HAU, CAU, GBI and candiduria were analysed. The need for strict
      monitoring of burned patients at risk for uroinfection development and the need
      to take urgent preventive measures is emphasized.

PMID- 7718116
TI  - Perineal burns in males secondary to spouse abuse.
AB  - Male spouse abuse seems to be on the increase. Recognition of these injuries is
      often difficult as patients are reluctant to disclose the aetiology and press
      charges against the assailant. We identified a similar group of male patients who
      sustained burns to their external genitalia secondary to spouse abuse.

PMID- 7718117
TI  - Motor vehicle-related burns: a review of 107 cases.
AB  - Motor vehicles are a major cause of morbidity and mortality. Burn injuries
      sustained from motor vehicles form a small but important subgroup. The authors
      have reviewed the case notes of 107 patients with motor vehicle-related burns
      over a 13-year period. The age ranged from 18 months to 65 years and the male to
      female ratio was 4:1. The mechanisms of injury were variable, although four major
      categories could be identified. These accounted for 83 per cent of the cases. Car
      fires following road traffic accidents was the largest group accounting for 48.5
      per cent of cases. The remaining three groups were: motorcycle-related burns
      following road traffic accidents (6.5 per cent of cases), garage fire-related
      burns (15 per cent of cases) and car radiator-related burns (13 per cent of
      cases). Garage fire-related burns had the highest mortality of the four groups
      (25 per cent). This study demonstrated that garage fire burns are an important
      subgroup of motor vehicle-related burns.

PMID- 7718119
TI  - Evaluation of the effects of a new Water-Jel system on specific bacterial and
      yeast strains in laboratory conditions.
AB  - In three previous studies the Water-Jel (WJ) system was found to protect burn
      wounds from microbial contamination, to have excellent analgesic and cooling
      effects when used as a first-aid dressing and to be bactericidal to 15
      microorganisms including yeasts tested from the Ostrava Burn Unit. Now a new WJ
      system has been introduced without povidone iodine. An extensive bacteriological
      laboratory evaluation of the new WJ system showed quite clearly its excellent
      antimicrobial and antimycotic properties for 13 of the 15 strains of
      microorganisms tested, the only exceptions being Clostridium difficile and
      partially Streptococcus faecalis. In a preliminary study, the new WJ system was
      used for 24-48 h in 74 burned patients with superficial partial and deep partial
      skin thickness burns. In 89 per cent of them there were no signs of infection on
      their burn wound after 48 h. The new WJ system was well tolerated and no allergic
      reactions appeared.

PMID- 7718118
TI  - Burns mortality and hospitalization time--a prospective statistical study of 352
      patients in an Asian National Burn Centre.
AB  - A prospective study of 352 patients in an Asian National Burn Centre has been
      used to develop statistical predictive models for mortality and hospitalization
      time. The patients are largely of Asian origin. Total burn surface area (% TBSA)
      and presence of respiratory burns are significant independent predictors of
      mortality in the multiple logistic regression analysis with an accuracy of 98.3
      per cent. Age is not a significant predictor of mortality in our patients. Age, %
      TBSA, full thickness % TBSA and respiratory burns are significant independent
      predictors of length of stay in hospital with a R2 value of 0.57 in the multiple
      linear regression analysis. There were 16 deaths, many of whom had developed
      multiple complications, common causes of which were sepsis, bronchopneumonia,
      DIVC and multiorgan failure. The final causes of death were septicaemic shock in
      10 patients, extensive burns in four patients, ARDS in one patient and bleeding
      peptic ulcer in one patient. The development of these two mortality and morbidity
      predictive models is the first step in the evaluation of our results. These
      models have to be tested against a future set of patients. After confirmation
      they will aid in patient management, clinical audit, patient and family
      counselling. They will also serve as baseline standards for evaluation of new
      therapies, assist us in the allocation of resources and identifying the at-risk
      population for improvements in therapy.

PMID- 7718120
TI  - Burn injuries caused by fireworks: effect of prophylaxis.
AB  - During the New Year 1991-92, a total of 17 patients with burns caused by
      fireworks (an unprecedentedly high number) were admitted to the two Danish burns
      units. They were all males and all had carried the causative firework in their
      clothes; 88 per cent were minors, and 87 per cent of these had bought their
      fireworks themselves in ordinary shops. Fireworks described as 'whistles' were
      responsible in 88 per cent of the cases. Appeals to the authorities resulted in a
      change of the legislation in November 1992, allowing only whistles equipped with
      safety fuses. Altogether 25 tons of unauthorized fireworks were confiscated and
      destroyed before January 1993. Campaigns were conducted at all schools and in the
      media in November and December 1992 and 1993, giving information about the
      dangers of carrying fireworks close to the body. During the New Year 1992-93,
      only four children were admitted with firework burns; the number of patients was
      significantly lower than in the preceding New Year, as was also the extent of
      their burn injuries. Furthermore, the patients were all younger than the age
      group targeted by the school campaign. The following New Year 1993-94, only three
      children were admitted with minor burns caused by fireworks, confirming the
      effect of the prophylactic actions. We conclude that the prophylactic actions
      were effective enough to reduce the number and severity of burn injuries caused
      by fireworks.

PMID- 7718121
TI  - Hot water burns in Cape Town.
AB  - Scalds are common in South Africa and accounted for 21.6 per cent of the
      admissions to the Burns Unit of the University of Cape Town. Two hundred and
      forty adult patients (160 males, 80 females) with a mean age of 34.2 years were
      admitted for treatment of scalds between 1985 and June 1992. One hundred and
      thirteen sustained their scalds accidentally while 127 patients were assaulted
      with hot water. Epilepsy accounted for 11 per cent of the accidental burns. The
      head and neck was involved in 16.8 per cent of accidental burns and in 84.9 per
      cent of assaults. A quarter of the scalds to the trunk and limbs were caused by
      assault compared with 75 per cent caused by accidents. Beta haemolytic
      streptococcus was the second commonest organism isolated from the burn wound (57
      patients). In 19 per cent of these patients a weekly course of penicillin and
      erythromycin did not eradicate the streptococcus and clindamycin was required.
      Accidental scalds usually affect the lower body and limbs whereas assault with
      hot water commonly involves the head and neck. Streptococcus is a common organism
      in the Burns Unit and is becoming more difficult to eradicate.

PMID- 7718122
TI  - Tannic acid as a topical agent in burns: historical considerations and
      implications for new developments.
AB  - The usage of tannic acid (TA) as a topical agent in burns in the past and the
      present is described. Its introduction by Davidson in 1925 led to the widespread
      use of TA. The high infection risk during times of war and reports of liver
      damage after application of high doses of undefined TA mixtures brought discredit
      to the TA treatment. German and Chinese authors have been able to refute these
      claims and propagate a safe therapeutic regimen. Recent animal experimental and
      clinical investigations confirm the many advantages: pain reduction, rapid
      haemodynamic stabilization, delayed primary excision, early mobilization and good
      cosmetic results.

PMID- 7718123
TI  - Emergency management of major hydrofluoric acid exposures.
AB  - Exposures of as little as 2.5 per cent of the body surface to concentrated
      hydrofluoric acid (HF) may be fatal. Survival after major HF exposures is
      facilitated by aggressive emergency management which, we feel, includes wound
      irrigation, subeschar injection of calcium gluconate, monitored supplementation
      of serum calcium, and prompt wound excision carried out as an emergency
      procedure. The following case reports and literature review illustrate the
      important differences between exposures to concentrated HF of as little as 2 per
      cent of the body surface and smaller exposures to concentrated HF or exposure to
      dilute HF.

PMID- 7718124
TI  - Oro-maxillofacial skeletal deformities resulting from burn scar contractures of
      the face and neck.
AB  - The deforming forces of the scar contracture associated with burns of the head
      and neck region involve primarily the skin and secondarily the facial
      musculoskeletal structures. A case of severe face and neck burn accompanied by
      extreme facial skeletal deformity is reported. Best results are obtained in
      patients treated properly and promptly by a team including plastic and
      maxillofacial surgeons as well as orthodontists.

PMID- 7718126
TI  - Bilateral amputations following hydrotherapy tank burns in a paraplegic patient.
AB  - Hydrotherapy is an important part of wound care and physical therapy. The
      benefits of hydrotherapy are derived from water's cleansing ability, buoyancy,
      drag, inertia and temperature. If the temperature of the water is not adequately
      controlled, an immersion scald burn can occur. A paraplegic patient who was
      receiving hydrotherapy for treatment of his malleolar ulcers sustained immersion
      scald burns that ultimately necessitated below-the-knee amputations.

PMID- 7718125
TI  - Effect of EGF dosage forms on alkali burned corneal wound healing of mice.
AB  - The local treatment effects of EGF forms on alkali burned mice corneal wounds
      were identified. The corneal wounds were induced by 0.5 M NaOH solution on the
      corneal surfaces of the mice. The local epidermal growth factor solutions (100
      ng/ml) and gel form in 0.2 per cent w/w carbopol 940 (100 ng/ml) were dropped in
      5 microliters aliquots into the eye twice a day. The corneal wounds were measured
      for 15 days at 7-day intervals and examined histologically at the end of 15th day
      of the experimental period. The results indicated that topical epidermal growth
      factor treatment in solution improved the healing of alkali burned corneal wounds
      when compared with epidermal growth factor delivered in a polymer system.

PMID- 7718127
TI  - Metastatic endophthalmitis in a patient with major burns: a rare complication.
AB  - A patient with 75 per cent of the body surface area burned developed metastatic
      endophthalmitis with orbital cellulitis leading to panophthalmitis in the right
      eye. In an estimated 1700 patients with burns treated in the same hospital over a
      period of 9 years (1984 to 1993), this is the first patient developing metastatic
      endophthalmitis. A possible pathological basis for the sequence of events is
      discussed.

PMID- 7718128
TI  - Recent references.

PMID- 7718130
TI  - [Protection of common peony from scarab damages].
AB  - The key to the protection of common peony from insect pests in the field is to
      control the damage done by Holotrichia oblita. An experimental study has been
      carried out on the prevention of adult pests in the field as well as on the
      prevention of pest larvae before planting and throughout the growing period of
      common peony. As a result a technological program for this particular pest
      prevention and elimination is proposed.

PMID- 7718129
TI  - [Pharmacognostical identification and investigation of commercial product of
      traditional Chinese drug jiuyanduhuo].
AB  - Through investigation on original plants and commercial products of the
      traditional Chinese drug Jiuyanduhuo, the authors have ascertained its botanical
      origin and present medicinal usage, and found out that Aralia cordata is the main
      species of Jiuyanduhuo, and A. fargesii is another species that has come into use
      due to short supply of the main species, and A. henyri is used only in Sichuan
      and Hubei Provinces. Principal identification features of the original plants and
      crude drugs with 2 keys have been given, and TLC identification for 3 kinds of
      Jiuyanduhuo have also been carried out.

PMID- 7718131
TI  - [Tissue culture of Pinellia ternata (Thunb.) Breit].

PMID- 7718132
TI  - [Comparison between essential oils and amino acids in fresh and processed roots
      of Changium smyrnioides Wollf].
AB  - This paper deals with a comparative study between essential oil and amino acid
      constituents from the fresh root and processed product of Changium smyrnioides.
      Twenty-seven ingredients were identified from the essential oil, and the amino
      acids in roots pro- and postprocessed were found varying greatly in content.

PMID- 7718134
TI  - [Chemical constituents of roots, rhizomes and stems of Amomum villosum Lour].
AB  - Ethyl octacosate, docosyl hexylate, a new compound stigmast-4-ene-1,3-dione, beta
      sitosterol and daucosterol were isolated and identified from the roots and
      rhizomes of Amomum villosum cultivated in Xishuangbanna, Yunnan. Two compounds
      daucosterol and emodin monoglycoside were isolated and identified from the stems
      of A. villosum.

PMID- 7718133
TI  - [Experimental study on the processed drug of castor seeds in the therapy of
      pulmonary carcinoma].
AB  - In this study, castor seeds were processed by one of the traditional Chinese
      methods, LD50 was measured and tumor inhition tests in nude mice bearing human
      pulmonary carcinoma were conducted. The results showed that the processing method
      was able to lower the toxicity of castor seeds and maintain their antitumor
      effect, thus providing an experimental basis for oral administration of castor
      seeds in the therapy of pulmonary carcinoma.

PMID- 7718135
TI  - [Analysis of essential oil in Chinese herb Saruma henryi Oliv].

PMID- 7718136
TI  - [Determination of loganin in Cornus officinalis Sieb. et Zucc. by TLC scanner].
AB  - The content of loganin extracted from Cornus of ficinalis was determined directly
      on a CS-930 TLC scanner. The method is simple and sensitive, and can serve as an
      index for checking the quality of C. of ficinalis.

PMID- 7718137
TI  - [Experimental studies on the effects of danggui buxue decoction on IL-2
      production of blood-deficient mice].
AB  - Danggui Buxue Decoction has shown the effect of significantly promoting the
      splenic capacity of blood-deficient mice in interleukin-2(IL-2)production (P <
      0.001). Individual analysis of herbal formula has shown that IL-2 production can
      be promoted in splenic lymphocytes of blood-deficient mice given Angelica
      sinensis or Astragalus membranaceus (P < 0.001).

PMID- 7718138
TI  - [Effects of radix Astragali on hemopoiesis in irradiated mice].

PMID- 7718139
TI  - [Effects of ginsenoside B on isolated atrium of guinea pigs].
AB  - It was found that Ginsenoside B (GSB) could reduce the myocardial systolic power
      and frequency of the isolated atrium of guinea pigs in a concentration-dependent
      way, and obviously prolong the functional refractory period of the left atrium.
      GSB could competitively antagonize the positive inotropic action of Iso, and non
      competitively antagonize the positive inotropic action of CaCl2 on the isolated
      right atrium of guinea pigs.

PMID- 7718140
TI  - [Effects of the leaves of Acanthopanax senticosus (Rupr. et Maxim.) Harms. on
      myocardial infarct size in acute ischemic dogs].
AB  - Effects of saponin isolated from the leaves of Acanthopanax senticosus (ASS) on
      myocardial infarct size were studied in acute ischemic dogs. The results showed
      that ASS (in a dosage of 25.50 mg/kg, iv) could significantly reduce the sizes of
      acute myocardial infarcts and decline the serum CK and LDH activity at 6h after
      ligation of LAD. It could also decrease the serum FFA levels at 3h and 6h after
      LAD occlusion.

PMID- 7718141
TI  - [Bacteriostasis of rhizoma Coptidis combined with trimethoprim (TMPO)].
AB  - The agar-dilution method was adopted to study contrastively the bacteriostasis of
      Rhizoma Coptidis and TMP, and also of the two drugs in combination. The results
      indicate that the combination works in good cooperation against Escherichia coli,
      Bacillus pyocyaneus, Staphylococcus aureus, Shigella flexneri and S. dysenteriae.

PMID- 7718143
TI  - [Progress in current studies on materia medica: leeches].

PMID- 7718142
TI  - [Efficacy of Phyllanthus spp. in treating patients with chronic hepatitis B].
AB  - The efficacy of Phyllanthus amarus produced in india, P. niruri gathered from
      hainan province and P. urinaria from henan province was assessed in a total of 88
      cases of chronic hepatitis B with 11.42 and 35 each. It was shown that P.
      urinaria had the effect of seroconversion on HBeAg from positive to negative as
      well as on HBeAb from negative to positive, while the other two herbs had not. In
      addition none of these three herbs had similar effect on HBsAg.

PMID- 7718144
TI  - Neural substrates for conditioned taste aversion in the rat.
AB  - Conditioned taste aversions (CTAs) are well known to be robust and long-lasting
      instances of learning induced by a single CS (taste)-US (malaise) pairing. CTA
      can be taken as a general model to search for neural mechanisms of learning and
      memory. In spite of extensive research on CTAs using a variety of approaches
      during the last three decades, the neural mechanisms of taste aversion learning
      still remain unsolved. In this article we propose a model of neural substrates of
      CTAs on the basis of our recent studies incorporating previous findings by other
      workers. Our studies mainly included experiments using ibotenic acid injections
      into various parts of the rat brain as a lesion technique, and c-fos
      immunohistochemistry in naive and CTA trained rats. CTAs were established by
      pairing the ingestion of saccharin (CS) with an ip injection of LiCl (US).
      Behavioral studies have shown that the parabrachial nucleus (PBN), medial
      thalamus, and basolateral nucleus of the amygdala are essential for both
      acquisition and retention of CTAs. C-fos studies suggested that association
      between gustatory CS and visceral US takes place in the PBN. The gustatory cortex
      (GC) may modify the strength of this association depending on the nature of the
      CS, viz., novel or familiar. The amygdala is indispensable for the expressions of
      CTAs. Tastes with hedonic values are stored in the GC in a long-term manner.

PMID- 7718146
TI  - The impact of inter-pellet interval and polydipsia on hypoalgesia elicited by non
      contingent food delivery.
AB  - Exposure to non-contingent food delivery has been shown to elicit an increase in
      nociceptive thresholds in rats. The conditions which elicit analgesia are similar
      to those that elicit schedule-induced polydipsia. In both instances animals are
      food-deprived and receive food on an intermittent schedule. Interpellet interval
      has been found to be an important predictor of schedule-induced polydipsia.
      Experiment 1 therefore investigated the effect of varying the interval between
      pellet deliveries on tail flick latencies in rats. The relationship between
      nociceptive threshold and inter-pellet interval was found to be bitonic in nature
      given that animals submitted to fixed time schedules of 30 or 60 s, but not 15 or
      120 s, exhibited significant increases in tail flick latencies. Experiment 2
      examined the effect of providing animals with water during exposure to non
      contingent food delivery. Under these conditions animals exhibited polydipsic
      behaviour, the development of which attenuated the hypoalgesic response to non
      contingent food delivery.

PMID- 7718145
TI  - The selective CCK-B agonist, BC 264, impairs socially reinforced memory in the
      three-panel runway test in rats.
AB  - The role of CCK-B receptor activation in memory processes has been reassessed
      using the three-panel runway task, under conditions which avoid the effects of
      CCK on satiety and reduce emotional responses. For this purpose the food
      reinforcement usually used was replaced by a social reinforcement. The results
      show that learning and memory can be assessed using this procedure. Moreover,
      under these experimental conditions, drugs such as scopolamine, amphetamine or
      kinurenic acid injected into the nucleus accumbens produced behavioral deficits.
      BC 264, a highly selective CCK-B agonist, peripherally administered or infused
      into the anterolateral part of the nucleus accumbens also impaired memory. These
      effects were suppressed by L-365,260 supporting the involvement of CCK-B
      receptors and of the nucleus accumbens in memory processes.

PMID- 7718147
TI  - Water maze performance and hippocampal weight of prenatally stressed rats.
AB  - Prenatally stressed rats were tested for water maze performance with the water
      temperature kept at 18 degrees C (low stress) or cooled down to 12 degrees C
      (high stress). When the platform had been removed from the pool and the water was
      kept at 12 degrees C, prenatally stressed males--but not females--spent more time
      searching for the platform in the correct quadrant of the pool than their
      controls. Prenatal stress reduced hippocampal weight in both sexes.

PMID- 7718148
TI  - Local and global perception examined by reversible suppression of temporal cortex
      with cold.
AB  - We placed cryodes over both sides of the dorsal inferotemporal cortex (TEd) in
      three monkeys in order to suppress its functions during perception of compound
      visual images. We used three pairs of images in a concurrent visual
      discrimination: 1. Congruent pair, a large T made of small Ts and a large 7 made
      of small 7s with response to the large 7 rewarded. 2. Incongruent pair, a T made
      of small 7s and a 7 made of small Ts with response to the large 7 rewarded. 3.
      Random pair, a scattering of small Ts in one stimulus and small 7s in the other
      with response to the small 7 rewarded. If TEd processes the global but not the
      local elements of a visual figure, animals with TEd suppressed should see only
      the local figures and they would fail only on the incongruent stimulus.
      Alternatively, if TEd processed the local, but not the global elements, they
      should fail only on the scattered small figures where there was no global element
      as a cue. Finally, if TEd suppression impairs discrimination of forms, they
      should be impaired on all the figures because they were the same form, but
      different size. We found that during TEd suppression, the animals failed on the
      scattered small elements, but not on the global figures formed of the small
      elements.

PMID- 7718149
TI  - Retrieval of color and form during suppression of temporal cortex with cold.
AB  - Five cryodes were implanted on each side over the dorsal aspect of inferotemporal
      cortex (TEd) of three monkeys. They were trained on a form discrimination and
      three color discriminations. Suppression of TEd with cold disrupted retrieval of
      the color, but not the form discriminations. The animals could find the colors in
      a background of shifting values of gray, indicating that the suppression did not
      reduce their color perception to gray. They initially had great difficulty
      matching red to red and green to green, although that recovered with experience.
      The animals tended to respond to one or the other of the colors, indicating that
      they could perceive and discriminate them, but, either lost information about the
      correct stimulus, or something from past experience was interfering with
      performance. We suggested that cooling TEd suppresses new and recent learning of
      color discriminations, but it does not suppress some previous experience that
      intrudes upon performance of new tasks. TEd might contain episodic information
      about colors necessary for performance of the immediate task.

PMID- 7718150
TI  - Mediodorsal thalamic lesions impair acquisition of an eyeblink avoidance response
      in rabbits.
AB  - Rabbits received ibotenic acid lesions of the mediodorsal nucleus of the thalamus
      (MD) or sham lesions. These animals were compared on four sessions of
      instrumental avoidance conditioning, during which an eyeblink (EB) response
      during the presentation of a tone-conditioned stimulus prevented the occurrence
      of a paraorbital electric shock unconditioned stimulus. Lesions of MD retarded
      acquisition of the EB avoidance response, but did not affect asymptotic
      performance. Concomitant heart rate (HR) changes were little affected by MD
      lesions, although there was some evidence that such changes were slightly larger
      in MD-lesioned animals. These results suggest that MD participates in some
      general aspect of the learning process, perhaps by affecting other behavioral
      processes such as 'attention' or 'arousal'.

PMID- 7718151
TI  - Effects of ibotenic acid lesions of the nucleus accumbens on instrumental action.
AB  - In a series of studies, we assessed the effects of ibotenic acid lesions of the
      nucleus accumbens on instrumental performance in hungry rats. Although these
      lesions were found to generally impair lever press performance for both food
      pellets and a sucrose solution, they did not affect sensitivity to changes in the
      incentive value of the outcome induced either by a shift in food deprivation or a
      shift in the sucrose concentration. Further, these lesions did not affect
      sensitivity to a change in the instrumental contingency from response-contingent
      to non-contingent outcome delivery. In contrast, concurrent assessment of food
      magazine approach responses found that the lesion induced both a deficit in
      magazine entry and marked insensitivity to shifts in the incentive value of the
      outcome and to the changed situation that accompanied the change in instrumental
      contingency. These results are interpreted as suggesting (1) that nucleus
      accumbens lesions produce a general deficit in affective arousal; and (2) that
      the influence of affective mechanisms on instrumental performance may be
      structurally dissociated from the control of performance mediated by the action
      outcome relation.

PMID- 7718152
TI  - Diurnal differences in L-tryptophan sleep and temperature effects in the rat.
AB  - Sleep/waking and EEG power spectra were investigated for 6 h periods in rats
      following administration of the essential amino acid L-tryptophan (40 mg/kg), the
      selective serotonin uptake inhibitor zimeldine (20 mg/kg), and following a
      combination of L-tryptophan and zimeldine. In contrast to earlier studies, L
      tryptophan decreased waking and increased total slow wave sleep when administered
      late in the light phase (8 1/2 h after light onset). No sleep effects were seen
      after early light phase injections (2 h after lights on). In agreement with
      earlier studies, zimeldine initially increased wakefulness, followed by an
      increase in slow wave sleep-2. REM sleep was abolished after zimeldine treatment.
      Zimeldine increased EEG delta activity and decreased EEG activity above 7 Hz. L
      Tryptophan potentiated the zimeldine induced increase in waking only when given
      early in the light phase. In a separate experiment, body temperature was
      monitored after L-tryptophan injections in both early and late light phase. A
      thermogenic effect of L-tryptophan was seen in the early light phase, while the
      opposite was seen in the late light phase. The data indicate diurnal differences
      in sleep/waking and temperature effects of a physiological dose of L-tryptophan.

PMID- 7718153
TI  - A comparative study of self-administration of morphine into the amygdala and the
      ventral tegmental area in mice.
AB  - BALB/c mice were unilaterally implanted with a guide-cannula, the tip of which
      was positioned 1.5 mm above either the amygdala (AMY) or the ventral tegmental
      area (VTA). On each experimental day, a stainless-steel injection cannula was
      inserted into these structures in order to compare the self-administration of two
      doses of morphine (5 ng or 50 ng) in independent groups using a spatial
      discrimination task in a Y-maze. During the acquisition phase, both AMY and VTA
      injected mice showed a regular self-administration response at the two doses
      used. The latency to trigger the injection was short, particularly in the VTA
      group. Subcutaneous injection of naloxone (4 mg/kg) in trained mice reduced the
      number of self-administrations to a level near to chance in both groups, which
      suggests that the drug-seeking behavior observed is effectively dependent on an
      opiate receptor-mediated mechanism. However the rate of extinction was more rapid
      in AMY than in VTA injected mice. The 'perseveration' response exhibited by the
      VTA group during the withdrawal precipitated by naloxone may probably be due to
      the strong motivational and/or rewarding effect of morphine when injected in this
      brain structure during acquisition.

PMID- 7718154
TI  - Tetrodotoxin blockade of amygdala overlapping with poisoning impairs acquisition
      of conditioned taste aversion in rats.
AB  - The role of several forebrain structures in the association of the short-term
      gustatory memory (GSTM) of the conditioned stimulus (CS; 0.1% sodium saccharin)
      with the visceral unconditioned stimulus (US; 0.15 M LiCl, 2% b.wt.) in
      acquisition of conditioned taste aversion (CTA) was investigated. Experiment 1
      examined the effects of bilateral reversible inactivation of amygdala (Amy),
      hippocampus (Hipp), gustatory cortex (GC), bed nucleus of stria terminalis
      (BNST), lateral hypothalamic area (LHA), ventral thalamus (VT) or LHA+VT, induced
      by intracerebral injection of tetrodotoxin (TTX; 10 ng/microliters per site)
      applied before i.p. injection of LiCl to rats anesthetized by pentobarbital (50
      mg/kg) immediately after saccharin drinking. Amy blockade resulted in a complete
      disruption of learning, while the inactivation of the remaining areas examined
      produced mild or no impairments. The dose-related effects of TTX injection into
      Amy were investigated in Experiment 2. Doses of 3 and 1 ng TTX were as effective
      as the 10 ng dose used in Expt. 1. However, 0.3 ng or saline did not interfere
      with CTA acquisition. Analysis of the retrograde amnesic effect produced by
      transient amygdalectomy (Experiment 3), showed that TTX (10 ng) injected
      immediately or 1.5 h after LiCl application induced a marked learning disruption,
      whereas no amnesia was elicited at 6 and 24 h post-acquisition intervals. It is
      suggested that Amy plays an essential role in the associative phase of
      acquisition, but not in the consolidation of the permanent taste aversion engram.

PMID- 7718155
TI  - Anhedonia or anergia? Effects of haloperidol and nucleus accumbens dopamine
      depletion on instrumental response selection in a T-maze cost/benefit procedure.
AB  - Two experiments were conducted to study the role of dopamine in the performance
      of a novel cost/benefit procedure. Rats were trained on a T-maze task in which
      one arm contained a high reinforcement density (4 x 45 mg Bioserve pellets) and
      the other arm contained a low reinforcement density (2 x 45 mg pellets).
      Different groups of rats were trained either with unobstructed access to both
      arms from the start area, or under a condition in which a large vertical barrier
      (44 cm) was placed in the arm that contained the high density of food
      reinforcement. In the first experiment, rats trained under each procedure
      received injections of 0.1 mg/kg haloperidol and tartaric acid vehicle as a
      control procedure. Analysis of variance indicated that there was a significant
      effect of the barrier on maze arm choice, a significant effect of haloperidol,
      and a significant drug x barrier interaction. Haloperidol did not affect arm
      choice in rats tested without the barrier present, but this drug significantly
      reduced the number of selections of the arm with high reinforcement density when
      the barrier was present. In the second experiment, groups of rats were trained as
      described above, and then received intraaccumbens injections of 6-hydroxydopamine
      or ascorbate vehicle. Nucleus accumbens dopamine depletions produced by 6
      hydroxydopamine decreased the number of selections of the arm with high
      reinforcement density when the barrier was present, but had no effect on arm
      choice when the barrier was not present.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718156
TI  - Antibody-conjugated magnetoliposomes for targeting cancer cells and their
      application in hyperthermia.
AB  - Magnetoliposomes for hyperthermia treatment of cancer were prepared by coating
      phospholipid on to magnetite particles. The optimum phospholipid composition for
      dispersibility was a phosphatidylcholine/phosphatidylethanolamine ratio of 2:1.
      The average size of the magnetoliposomes, which were aggregates of 10 nm core
      magnetite particles, was about 80 nm. The magnetoliposomes were coated with
      hydrazide pullulan to stabilize the phospholipid capsules and provide an anchor
      for the immobilization of antibodies. By this method, 90-180 molecules of a
      monoclonal antibody were immobilized on to a magnetoliposome particle. When the
      antibody-conjugated magnetoliposomes were incubated with cancer cells, they were
      adsorbed on to the cell surface and incorporated by the cells about 12 times more
      effectively than the control after 4 h. The amount of incorporated magnetite was
      0.61-3.6 pg/cell, depending on the antigen-antibody system. The heating
      properties of the magnetoliposomes were also measured and found to vary with the
      size of the core magnetite.

PMID- 7718157
TI  - Preparation of affinity sorbents and isolation of individual chitinases from a
      crude supernatant produced by Streptomyces kurssanovii by a one-step affinity
      chromatographic system.
AB  - The preparation of two affinity-chromatography sorbents based on cross-linked
      chitin are described. Both sorbents retained selectively one of the four
      extracellular chitinases in the culture supernatant produced by Streptomyces
      kurssanovii. Chitinases with molecular masses of 42 kDa and 26 kDa were isolated
      in homogeneous form using one-step affinity-chromatography procedures involving
      either a fully N-acetylated or a partially N-acetylated cross-linked chitin-type
      sorbent. Two other chitinases were not selectively bound by the sorbents and,
      therefore, were not isolated in a homogeneous form. The affinity sorbents were
      shown to be stable over the period of separation and could be used repeatedly.

PMID- 7718158
TI  - Stabilizing effect of water/alcohol solvents towards autoxidation of
      glutaraldehyde-modified haemoglobin.
AB  - Glutaraldehyde-cross-linked haemoglobin is potentially very attractive as a
      useful oxygen carrier for biomedical and technological purposes. However, its
      oxygen-binding ability is restricted by the autoxidation of the iron which is
      faster than for native haemoglobin. We have studied the stabilization effect of
      ethanol, butan-1-ol, ethylene glycol and glycerol on the autoxidation of
      glutaraldehyde-cross-linked oxyhaemoglobin. We have shown that, in the presence
      of water/alcohol mixtures, cross-linked haemoglobin became more stable towards
      autoxidation than native oxyhaemoglobin in an aqueous environment. From a
      structural point of view, an e.p.r. study showed that alcohols and cross-linking
      had opposite effects on the haem environment. In contrast with the cross-linking,
      alcohols stabilize oxyhaemoglobin by decreasing the charge transfer from the iron
      to the oxygen, decreasing the O-O length and increasing the total distance (F8
      His)-N-F-O2.

PMID- 7718159
TI  - Immobilization of Aspergillus niger xylanase on magnetic latex beads.
AB  - Xylanase from Pectinex 3XL was purified 70-fold by precipitation with an enteric
      polymer, Eudragit S-100. The purified xylanase was immobilized on magnetic latex
      beads via carbodi-imide coupling. The immobilized preparation showed 80% of the
      total activity bound to the beads. The pH optimum remained unchanged at 6.0 and
      the Km increased from 0.25 g/100 ml (free enzyme) to 0.39 g/100 ml on
      immobilization. Immobilization resulted in significant thermal stability at 60
      degrees C. The time course of hydrolysis of xylan at 60 degrees C by free enzyme
      as well as immobilized enzyme was also studied.

PMID- 7718160
TI  - Characterization, subsite mapping and partial amino acid sequence of glucoamylase
      from the filamentous fungus Trichoderma reesei.
AB  - The pH optimum, temperature-dependence, thermal stability, substrate specificity
      and subsite affinities of the 66 kDa, pI 4.0 glucoamylase of the filamentous
      fungus Trichoderma reesei were determined. It had a pH optimum of 5.5 and a
      temperature optimum (5 min reaction time) of 70 degrees C with soluble starch as
      substrate. Thermal-inactivation studies revealed that the glucoamylase is
      relatively thermostable up to 60 degrees C. Metal ions and EDTA tested at 5 mM
      concentrations had no significant effect, and beta-cyclodextrin only slightly
      inhibitory effects, on the digestion of soluble starch. Estimated Km and kcat.
      values for soluble starch where 0.11 mg.ml-1 and 28.5 s-1 respectively.
      Hydrolysis of pullulan (Km 14 mg.ml-1 and kcat. = 6.6 s-1) indicated substantial
      activity towards 1,6-O-glucosidic bonds. From ratios of kinetic parameters of
      malto- and isomalto-oligosaccharides, it was apparent that the glucoamylase
      showed approx. 3-fold higher selectivity towards isomalto-oligosaccharides than
      most other reported fungal glucoamylases. Substrate binding affinities were
      calculated from kinetic data for the linear series of malto- and isomalto
      oligosaccharides. The results were in good agreement with other reported
      glucoamylases. The main difference was that subsite 1 showed a slightly negative
      free energy of binding with malto-oligosaccharides, whereas most other
      glucoamylases show a positive free energy at this subsite. A set of peptides
      obtained from purified glucoamylase by tryptic digestion where sequenced. They
      covered approx. 17% of the total amino acid sequence as estimated from molecular
      mass on SDS/PAGE. Some of the sequences were tentatively aligned to known
      glucoamylase sequences. They showed about 60% identity with the extensively
      studied Aspergillus glucoamylase.

PMID- 7718161
TI  - Neurosurgery in the elderly.

PMID- 7718162
TI  - Facial and acoustic nerve preservation during excision of extracanalicular
      acoustic neuromas using the suboccipital approach.
AB  - The results are presented from a consecutive operative series of 62 acoustic
      neuromas in 60 patients following the introduction of improved neurophysiological
      monitoring techniques. Twenty-two patients had usable preoperative hearing.
      Thirty tumours were less than 2.5 cm diameter and 32 greater in size. Operation
      was via a 3-4-cm diameter retromastoid craniectomy. The internal auditory meatus
      was opened by an ENT surgeon (RM) using a drill and the facial nerve identified
      by stimulation. The tumour was then centrally evacuated by a neurosurgeon (MT/HC)
      using an ultrasonic aspirator, and the thin exterior part of the tumour carefully
      dissected off the nerves in or around the capsule with constant stimulation and
      monitoring of facial EMG, BSAEP and electrocochleography. A new type of
      stimulation probe has been designed and coupled to a stimulator/integrator/tone
      burst generator (SB) so that continuous immediate direct feedback to the surgeon
      is possible. A variable amplitude discriminator rejects baseline EMG (> 50
      microV) and a gating circuit prevents stimulus artefact (during monopolar
      stimulation) from causing interference. By these means the VII nerve could be
      identified even when translucent and undefinable as a nerve bundle. Anatomical
      preservation was possible in 98% of VII nerves. Full facial function was present
      in 20 cases immediately postoperatively. Full delayed recovery occurred in 23
      cases giving an eventual total in House Grade I of 69%. Seven other cases
      recovered to House Grade II. There was therefore 81% satisfactory facial nerve
      function. This percentage is exactly the same for larger and for smaller tumours.
      Anatomical preservation of the VIII nerve was achieved in 24/62 (39%) of the
      whole series and 11/16 (69%) of those with a hearing loss of < 50 dB. Functional
      preservation of hearing described as usable by the patient (< 65 dB) was achieved
      in 7/22 cases (32%), 3/13 (23%) in tumours < 2.5 cm and 4/9 (44%) in those > 2.5
      cm diameter. Hearing preservation of < 50 dB in patients with preoperative
      hearing threshold < 50 dB and tumours of < 2.5 cm was 3/11 (27%). Monitoring by
      BSAEP and ECochG was technically unsatisfactory because the responses were
      affected by drilling and stimulation. Acoustic nerve preservation should be
      attempted in all cases with measurable hearing, regardless of tumour size.

PMID- 7718163
TI  - Growing skull fractures: classification and management.
AB  - Seven patients with growing skull fractures treated between 1983 and 1993 are
      described. These growing fractures constituted 1.6% of all the cases of skull
      fractures seen during the period (a total of 449 cases). Based on
      aetiopathogenesis, computed tomography (CT) appearances, operative findings and
      management strategies required, three main types of growing skull fractures were
      recognized. In type I (n = 3) a leptomeningeal cyst, in type II (n = 3) damaged
      and gliotic brain, and in type III (n = 2) a porencephalic cyst extended through
      the skull defect into the subgaleal space. A combination of type I and type III
      co-existed in one patient. Initial head injury and neurological deficit were
      judged to be mild to moderate in all the seven cases. Continued growth of skull
      fractures correlated closely to the increasing neurological deficit in five
      cases. In two patients natural arrest of fracture growth at 5 and 7 months after
      trauma was accompanied by arrest in progress of neurological deficit. Available
      surgical options are discussed and general guidelines for the management are
      given.

PMID- 7718164
TI  - Pleomorphic xanthoastrocytoma--report of four cases, with MRI scan appearances
      and literature review.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a rare glial tumour typically occurring in
      young patients in the first three decades, having a superficial cortical location
      and with a relatively good prognosis for long-term survival. Four cases are
      reviewed. The magnetic resonance imaging (MRI) appearances, which in PXA have
      been reported only once before, are described in three cases. The fourth case was
      studied by computed tomography and angiography. One patient developed seizures at
      age 2 days and was aged 2 1/2 years at presentation. This is the youngest patient
      with PXA yet reported. Three of the four patients had seizures, but in one case
      the tumour was not the cause of the seizures. Review of the literature has
      revealed 47 reported cases. Mean age at presentation was 14.3 years. Epilepsy
      occurred in 78%. Seventeen patients were alive without recurrence at a mean of
      7.9 years after diagnosis and 10 patients died at a mean of 7.4 years after
      diagnosis. Thirteen cases had recurrence at a mean of 6 years after surgery and
      in five instances the recurrence was in the form of a glioblastoma. Resections
      which were grossly total were less likely to develop recurrence than those which
      were subtotal. Complete gross resection of tumour offers the best therapeutic
      option in PXA.

PMID- 7718165
TI  - Clostridial brain abscesses.
AB  - Ten patients with clostridial abscesses of the brain are presented. Despite the
      presence of gas within the cerebral hemispheres and Clostridium welchii cultured
      from the pus obtained, the outcome of all patients managed with burrhole
      aspiration of the abscess was good. There were no deaths and eight of the ten
      patients had no residual deficit. Clostridial infections of the brain, unlike
      those of the soft tissues of the body, have a good outcome with conservative
      surgery and appropriate antibiotics.

PMID- 7718166
TI  - Haemostatic derangement in patients with intracranial tumours.
AB  - Forty-five patients with brain tumours were studied for evidence of any
      haemostatic abnormalities in the preoperative and intraoperative period. An
      abnormality was found in 44 of the patients in the preoperative period and in all
      the patients during the operation. One patient developed acute disseminated
      intravascular coagulation. A change in the haemostatic abnormality from the
      preoperative to the intraoperative period was demonstrated in 9 of the patients.
      The histological nature of the tumour did not influence the haemostatic
      derangement. A shortened euglobulin lysis time, prolonged thrombin time,
      increased fibrin degradation products and abnormal fibrinogen levels were the
      common isolated abnormalities. When considered together, chronic disseminated
      intravascular coagulation (DIC) with or without fibrinolysis and fibrinolysis
      with or without DIC were the commonest abnormalities. Although some degree of
      haemostatic derangement is found in a high proportion of patients with brain
      tumours, clinically relevant abnormalities are rare.

PMID- 7718167
TI  - Thecal repair in post-surgical pseudomeningocoele.
AB  - A postsurgical pseudomeningocoele (PSPM) forms when cerebrospinal fluid
      extravasates through a dura-arachnoidal tear and becomes encysted within the
      wound. Patients may become symptomatic with wound swelling, headache and
      radiculopathy. A uniform method of repairing PSPMs is described which includes
      separation of the dura from the arachnoid, dural repair under operating
      microscope control, and the use of overlapped local flaps to reinforce the dura
      and obliterate the PSPM sac. Four recent cases are presented which were
      successfully treated using this method.

PMID- 7718168
TI  - The combined method of transplantation of foetal substantia nigra and
      stereotactic thalamotomy for Parkinson's disease.
AB  - Five cases with late Parkinson's disease improved following treatment with a
      combination of foetal substantia nigra grafts and stereotactic thalamotomy. The
      average Webster's score decreased from 21 to 11 points. This modified method is
      simple, safe and effective.

PMID- 7718169
TI  - A phase I/II study of salvage radiosurgery in the treatment of recurrent brain
      metastases.
AB  - Radiosurgery has been advocated as a salvage treatment for relapsed patients with
      brain metastases. This report describes a phase I/II study of salvage
      radiosurgery for patients previously treated with whole brain irradiation. The
      study was opened in March 1989 and the last patient was treated in July 1992. All
      patients have been followed to recurrence at the radiosurgically treated site or
      to death. Twenty progressing metastases in 12 patients were treated using 14
      radiosurgical procedures. The radiation dose was always 25 Gy with the 90%
      isodose volume encompassing all enhancing tumour. Nineteen metastases were
      evaluable at +4 weeks. There were no instances of progressive disease; there were
      three complete responses, six partial responses, and 10 metastases remained
      unchanged. Median survival from the date of radiosurgery was 6 months. Nine of 12
      patients eventually failed at the radiosurgically treated site (two remain
      alive). Radiosurgery at the time of relapse provides temporary control of
      recurrent brain metastases with acceptable toxicity.

PMID- 7718170
TI  - An evaluation of the epileptogenic properties of a rifampicin/clindamycin
      impregnated shunt catheter.
AB  - A process has been developed by which ventriculoperitoneal hydrocephalus shunts,
      which are prone to bacterial colonisation, can be impregnated with antimicrobials
      in order to confer antibacterial activity. Concern that their use might be
      associated with an increased risk of postoperative seizures has been addressed
      here. Using two rat models, namely pentylenetetrazole (PTZ) and maximal
      electroconvulsive seizure (ECS) thresholds, the possible epileptogenic
      characteristics of the shunt catheters were determined. Animals implanted with
      impregnated catheters exhibited no significant difference in PTZ seizure
      threshold compared with controls. In contrast, the ECS threshold test showed an
      enhancement in seizure susceptibility in the non-impregnated catheter group, in
      accordance with that found in human subjects, but a significant reduction in the
      impregnated catheter group at 2 and 28 days, postoperatively. These data suggest
      that the use in human subjects of shunts impregnated with these antimicrobials
      will not increase the risk of postoperative seizures.

PMID- 7718171
TI  - Extended vascularized temporalis muscle-fascia flap.
AB  - The use of an extended vascularized temporalis muscle flap is described. The deep
      layer of the temporalis fascia is partially everted over the temporalis muscle
      preserving its vascularity. A composite flap comprising temporalis muscle and its
      fascia attached along its superior border, is rotated for reconstruction of
      postoperative defects in the middle cranial fossa floor and mastoidectomy
      cavities. The versatility of this flap is discussed.

PMID- 7718172
TI  - Prolymphocytic transformation of chronic lymphocytic leukaemia manifesting as a
      cerebellar lymphoma.
AB  - A 75-year-old woman presented with symptoms related to a space occupying lesion
      in the cerebellum which histology showed to be a malignant lymphoma of
      prolymphocytic type. A diagnosis of chronic lymphocytic leukaemia (CLL) had been
      made over 1 year before. This form of lymphoma complicating CLL has not been
      described previously in the nervous system.

PMID- 7718173
TI  - Cervical schwannoma presenting as a spinal subdural haematoma.
AB  - We report a case of cervical spinal subdural haematoma as the presenting
      manifestation of a small intradural schwannoma. In patients without a bleeding
      diathesis and an apparently spontaneous spinal subdural haematoma, the
      possibility of an underlying tumour should always be considered.

PMID- 7718174
TI  - Transoral plate and screw fixation of the craniovertebral region--a preliminary
      report.
AB  - A transoral plate and screw fixation of the clivus to the body of the cervical
      vertebra is described. The procedure was successfully performed in a patient with
      congenital basilar invagination after odontoidectomy.

PMID- 7718175
TI  - Tophaceous gout of the spine causing spinal cord compression.
AB  - Tophaceous gout of the spine rarely causes spinal cord compression. Only eight
      cases have been reported previously. We report a further case presenting with
      progressive quadriparesis caused by gouty tophi at C1, treated successfully by
      decompressive laminectomy and internal fixation. This case and the previously
      reported cases are reviewed.

PMID- 7718176
TI  - Incidentally discovered arteriovenous malformation of the anterior fossa dura.
AB  - Dural arteriovenous malformations (AVMs) are rare vascular abnormalities that
      most frequently involve the cavernous, transverse or sigmoid sinus. Anterior
      cranial fossa dural AVMs are uncommon. We report the clinical, radiological and
      surgical features of an incidentally discovered anterior fossa dural AVM. The
      literature regarding the anatomy and clinical presentation of this lesion is
      reviewed.

PMID- 7718177
TI  - Thoracic intraspinal lipoma.
AB  - Intraspinal lipomas are rare congenital tumours that most commonly occur at the
      conus. We describe a thoracic intraspinal lipoma presenting with a myelopathy and
      imaged by MRI. Surgical decompression and dural enlargement appears to be the
      treatment of choice in those patients who develop spinal cord dysfunction
      associated with an intraspinal lipoma.

PMID- 7718178
TI  - Posttraumatic myelopathy.

PMID- 7718179
TI  - Subependymomas of the lateral ventricles.

PMID- 7718180
TI  - Consequences of prolonged inhalation of ozone on F344/N rats: collaborative
      studies. Part X: Robust composite scores based on median polish analysis.
AB  - This report describes some of the statistical methods used to analyze data from
      the National Toxicology Program/Health Effects Institute Collaborative Ozone
      Project. The purpose of the collaborative study was to assess the health effects
      of chronic ozone inhalation. Data were obtained from a subset of 164 F344/N rats
      dedicated to use by the Health Effects Institute from a standard ozone inhalation
      study conducted by Battelle Pacific Northwest Laboratories for the National
      Toxicology Program. The study involved eight groups of investigators, each
      assessing different types of ozone-related health effects. These included studies
      of respiratory function and of structural, cellular, and biochemical changes in
      the lungs and airways. Designing and analyzing a study with several groups of
      investigators raises many statistical challenges. The highest design priority for
      this study was that each investigation be individually interpretable as an
      independent study. This meant that each investigator had to receive an adequate
      number of animals, balanced with respect to level of ozone exposure and other
      factors such as the gender of the rats and the time they were killed. Another
      feature of the collaborative study was the opportunity it provided to assess and
      quantify the effect of ozone exposure on a broad spectrum of endpoints, and to
      explore the relations between the different types of effect. Maximizing the
      potential to assess these correlations required that the individual animals
      studied by the different groups of investigators overlap as much as possible.
      This aspect of the statistical design required careful consideration of the
      compatibility between various investigations. Fortunately, the degree of
      compatibility was substantial. In many cases, for example, it was possible to
      assess respiratory function in the animals before they were killed, and then to
      divide the tissue among several different investigators. This report concentrates
      on the methods that were specially developed to analyze the data for multiple
      endpoints collected in the study. Nonstandard techniques were required to
      accommodate the complex pattern of missing data that was inherent in the study
      design because no animals were measured by all investigators.

PMID- 7718181
TI  - Consequences of prolonged inhalation of ozone on Fischer-344/N rats:
      collaborative studies. Part II: Mechanical properties, responses to bronchoactive
      stimuli, and eicosanoid release in isolated large and small airways.
AB  - Acute exposure to ozone has been shown to have deleterious effects on pulmonary
      function in normal humans and in all animal species studied to date. The goal of
      this study was to determine whether near-lifetime exposure to ozone alters the
      mechanical properties, the pharmacologic responses, or both, of airways isolated
      from F344/N rats, and to relate these properties to airway wall structure.
      Segments from approximately fourth-generation airways (representing large
      airways) and eighth-generation airways (representing small airways) were isolated
      from rats of both genders that had been exposed for six hours per day, five days
      per week to 0, 0.12, 0.5, or 1.0 parts per million (ppm)* ozone for 20 months.
      Using in vitro techniques, the airways were mounted on myographs and several
      parameters of airway function were evaluated. These included relationships
      between (1) passive tension and internal circumference of the airways, (2) active
      tension and internal circumference of the airways, and (3) responses of the
      airways to bronchoactive stimuli. The effects on these relationships of
      epithelial damage caused by lumenal abrasion of selected airway segments also
      were evaluated. Wall and smooth muscle areas were measured in these airways, and
      responses obtained from mechanical and pharmacologic studies were related to
      these morphological parameters. Eicosanoid levels were measured in media
      surrounding airway explants to determine whether near-lifetime exposure to ozone
      alters production of these important modulators of airway function. The relation
      between passive tension and internal circumference found in large and small
      airways was exponential in nature and unaffected by ozone exposure. The relation
      between active tension and internal circumference of isolated airways produced a
      curve characterized by active tension that increased with increasing
      circumference. This result reached a maximum and then decreased as the
      circumference increased further. The curve describing this relationship did not
      change after ozone exposure. The maximum effect was evident at the same point on
      each airway's passive tension and internal circumference relationship. Wall and
      smooth muscle areas measured in large airways were not affected by ozone
      exposure. The wall area increased, however, in small airways isolated from males
      after exposure to 0.5 ppm ozone. In addition, smooth muscle area increased in
      small airways isolated from rats exposed to 0.5 ppm ozone; this effect of ozone
      did not vary with gender. No differences in maximum active stress (active tension
      normalized to smooth muscle area) were detected in large airways after ozone
      exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7718182
TI  - Infant feeding policy and practice in the presence of HIV-1 infection.

PMID- 7718183
TI  - Retinoic acid inhibits both the basal activity and phorbol ester-mediated
      activation of the HIV long terminal repeat promoter.
AB  - OBJECTIVE: To establish whether the steroid hormone retinoic acid (RA) was able
      to modulate the activity of the HIV-1 promoter. DESIGN: The effect of RA and
      nuclear factor (NF)-kappa B on HIV-1 promoter activity was investigated using HIV
      1 long terminal repeat (LTR)-based reporter constructs. METHODS: The activity of
      wild type and mutant LTR sequences was compared in a variety of stably and
      transiently transfected human cell lines. RESULTS: It was shown that RA treatment
      inhibits both the basal activity of the HIV-1 LTR and its stimulation by phorbol
      ester treatment. This inhibition is observed in both HeLa cells (in the presence
      of exogenously supplied RA receptors) and the naturally RA-responsive U937
      monocyte cell line. RA can also inhibit the stimulation of the HIV-1 LTR by
      overexpression of NF-kappa B subunits, while linkage of the NF-kappa B sites in
      the HIV promoter to a heterologous promoter results in its inhibition by RA.
      CONCLUSIONS: The data presented clearly demonstrate a negative effect of RA on
      HIV-1 LTR activity that may contribute to its effect on viral replication.

PMID- 7718184
TI  - Long-term survival without clinical AIDS after CD4+ cell counts fall below 200 x
      10(6)/l.
AB  - OBJECTIVE: Quantify and study cofactors of long-term survival without AIDS in HIV
      1-infected individuals with CD4+ cell counts < 200 x 10(6)/l. DESIGN: Comparison
      of 579 participants who could be longitudinally evaluated for at least 3 years
      after the earliest date of first reaching a CD4+ cell count < 200 x 10(6)/l or an
      AIDS-defining illness (1987 Centers for Disease Control and Prevention
      definition). SETTING: Ongoing 9-year cohort study with data collected at 6-month
      intervals. PATIENTS: HIV-1-infected homosexual men. MEASUREMENTS AND MAIN
      RESULTS: Of the men, 20% did not develop an AIDS illness within 3 years following
      a confirmed CD4+ cell count < 200 x 10(6)/l; 29 and 28% were diagnosed with a
      first clinical AIDS illness from 1-3 and < 1 years, respectively, beyond their
      first CD4+ cell count < 200 x 10(6)/l; 23% were diagnosed with a clinical AIDS
      illness prior to their first CD4+ cell count < 200 x 10(6)/l. Slower decline of
      CD4+ cell count (P < 0.001) and presence of higher body-mass index during the
      period prior to the first CD4+ cell count < 200 x 10(6)/l (P < 0.001) predicted
      longer time to an AIDS illness once this threshold was reached. Most men had
      rapid loss of CD4+ cells, total T cells, and hemoglobin during the period after
      CD4+ cells declined below 200 x 10(6)/l. However, those remaining free of AIDS
      illnesses the longest arrested their decline in CD4+ cell counts and hemoglobin
      levels and increased total T cells during this period. Although antiretroviral
      therapy and Pneumocystis carinii prophylaxis extend AIDS-free survival, 45% of
      the group who were AIDS-free > or = 3 years after CD4+ cells fell below 200 x
      10(6)/l had not used these treatments. CONCLUSIONS: Significant numbers of
      individuals remain free of illnesses and AIDS symptoms > or = 3 years after CD4+
      cell counts drop below 200 x 10(6)/l. This occurs even in the absence of
      treatment. The associations seen here suggest that host and viral factors play
      important roles. Thus, further studies are needed to determine the biological
      basis of long-term survival without AIDS illnesses in HIV-1-immunosuppressed
      patients.

PMID- 7718185
TI  - Improved brain delivery and in vitro activity of zidovudine through the use of a
      redox chemical delivery system.
AB  - OBJECTIVE: Improved therapy for AIDS dementia and related encephalopathies may be
      achieved through enhanced delivery of effective antiretroviral agents to the
      central nervous system (CNS). DESIGN: A novel chemical delivery system (CDS) was
      used, which utilized redox trapping of drugs in the brain. This study was aimed
      at defining the pharmacokinetics of a zidovudine (ZDV)-CDS as well as
      establishing its in vitro antiviral efficacy against HIV in both lymphocytes and
      in a neural cell line. RESULTS: ZDV-CDS administered parenterally to rats
      produced significantly higher brain levels of ZDV [area under the curve (AUC),
      425 micrograms x min/g] than equimolar ZDV (AUC, 13.5 micrograms x min/g). Native
      ZDV uptake was minimal after 1 h when analyzed in CEM lymphocytes and in SKNMC
      neuroblastoma cell line. By contrast, marked uptake of ZDV-CDS was followed by
      biochemical conversion of ZDV-CDS to its main metabolites (ZDV-CDS quaternary
      salt, ZDV-Q+, and native ZDV). These improved uptake profiles were associated
      with greater in vitro virucidal effect. ZDV-CDS at 0.5 microM was 80% more
      effective than ZDV in suppressing p24 production in a lymphocyte culture infected
      with 6000 median tissue culture infective doses (TCID50) of the HIV N1T strain
      and 50% more effective at 0.05 microM. Furthermore, syncytia formation was
      completely suppressed at a ZDV-CDS dose of 0.5 microM (600 TCID50) but native ZDV
      at the same dose was ineffective. Finally, while ZDV (at 0.5 microM) is not
      active in reducing viral replication in an SKNMC neural cell line, the ZDV-CDS
      complex significantly suppressed p24 synthesis. CONCLUSION: The ZDV-CDS complex
      is capable of delivering higher ZDV doses to lymphocytes and neural cells, with
      improved antiretroviral activity.

PMID- 7718186
TI  - Response of HIV RNA to didanosine as a predictive marker of survival.
AB  - OBJECTIVE: To evaluate whether early changes in viraemia in response to
      didanosine (ddI) predict death and occurrence of new AIDS-defining events.
      METHODS: Forty-three patients were followed during ddI treatment with sequential
      determinations of serum viraemia, mutations associated with drug resistance, CD4
      counts and clinical evaluation. Patients were stratified into two groups of equal
      size, responders and nonresponders, using the median of individual changes in
      viraemia 1 month after initiation of ddI therapy. RESULTS: After 1 month of ddI,
      mean viraemia decreased by 0.35 log RNA copies/ml of serum (P < 0.001) in the
      population. A significant difference in survival (median, 14 and 35 months in
      nonresponders and responders, respectively; log rank, P = 0.004) and in the delay
      to the occurrence of new AIDS-defining events (median, 8 and 33 months in
      nonresponders and responders, respectively; log rank, P = 0.018) was observed.
      After stratification for presence of AIDS before starting ddI, viraemia response
      at 1 month remained predictive of both overall and AIDS-defining event-free
      survival (log rank, P = 0.0006 and P = 0.01). After a similar stratification for
      initial CD4, viraemia response still predicted overall survival (log rank, P =
      0.009), but its predictive value for AIDS-defining event-free survival did not
      reach statistical significance (P = 0.12). High initial levels of HIV RNA,
      presence of mutation 215 or previous duration of zidovudine therapy were not
      predictive of survival. CONCLUSIONS: In patients treated with ddI, changes in
      viraemia at 1 month predict survival independently of initial AIDS diagnosis and
      initial CD4 counts.

PMID- 7718187
TI  - HIV infection and drug use: influence on cognitive function.
AB  - OBJECTIVE: To examine the involvement of cognitive function in HIV-seropositive
      drug users (DU) in a pre-AIDS state. DESIGN: Fifty-six HIV-positive DU were
      prospectively evaluated. They belonged to groups II, III and IV (subgroups A, C2
      and E) of the 1987 Centers for Disease Control and Prevention classification,
      with anamnesis negative for neurological pathology. HIV-negative DU (n = 19) and
      non-DU (n = 27) were used as controls. Infection with HIV and use of toxic drugs
      were considered variables of influence on cognitive function. METHOD: Subjects
      underwent neuropsychological evaluation by tests designed to explore cortical and
      subcortical function. RESULTS: HIV-positive DU showed worse performance scores at
      the psychometric tests than HIV-negative non-DU, but there was no difference when
      compared with HIV-negative DU. Ex-DU showed better performance than active DU. No
      difference with regard to degree of disease evolution was observed among HIV
      positive individuals (i.e., groups II and III versus group IV). CONCLUSIONS:
      There was no evidence of cognitive deficits in HIV-positive individuals in non
      AIDS phases to indicate early involvement by HIV at the cerebral level.
      Progression of the disease, prior to the AIDS phase, did not determine a
      worsening of intellectual performance. Instead, cognitive function was affected
      by the chronic and current use of toxic substances. In HIV-positive DU, a decline
      in cognitive function was found to be attributable to the chronic use of toxic
      substances rather than HIV infection.

PMID- 7718188
TI  - Same-sex behavior, sexually transmitted diseases and HIV risks among young
      northern Thai men.
AB  - OBJECTIVES: To assess the risks for HIV infection and sexually transmitted
      diseases (STD) among young northern Thai men who have sex with men (MSM), and to
      examine the possible role of male same-sex behavior in the northern Thai HIV/AIDS
      epidemic. METHODS: Two cohorts of northern Thai military conscripts and one
      cohort of recently discharged conscripts, a total of 2047 men, were studied. Data
      were collected by interview on behavioral risk factors, and sera were examined
      for syphilis and HIV-1 antibodies. Univariate and multiple logistic regression
      analyses were used to determine risk factors associated with HIV and STD, and to
      assess the frequency and patterns of same-sex behaviors among these men. RESULTS:
      Of 2047 men, 134 (6.5%) reported one or more male lifetime sex partners. Of these
      MSM, 130 (97.0%) also had female partners, and four (3.0%) had exclusively male
      partners. Compared with men who reported only female sex partners, MSM had a
      higher number of lifetime sex partners, a higher mean number of female sex
      partners, more female and male commercial sex worker (CSW) partners, and were
      more likely to be married. MSM were significantly more likely than exclusively
      heterosexual men to report having had any STD [odds ratio (OR), 2.72], gonorrhea
      (OR, 2.05), syphilis (OR, 3.17), non-gonococcal urethritis (OR, 4.54) and penile
      discharges (OR, 6.24). They were at borderline increased risk for HIV infection
      [OR, 1.51; 95% confidence interval (CI), 0.95-2.41]. Men with more than one
      lifetime male sex partner compared with those with only one partner were
      significantly more likely to be HIV-infected (OR, 2.81; 95% CI, 1.09-7.19).
      CONCLUSIONS: Northern Thai MSM are a high-risk population for STD, including HIV.
      Reported same-sex behavior in this population appears to vary considerably with
      data collection techniques. HIV and STD prevention strategies aimed at changing
      unsafe sexual practices may need to be targeted to the general population of
      young Thai men.

PMID- 7718189
TI  - Increasing HIV-1 seroprevalence associated with genital ulcer disease, New York
      City, 1990-1992.
AB  - OBJECTIVE: To measure HIV seroprevalence trends associated with sexually
      transmitted diseases (STD) causing ulcerative lesions [genital ulcer disease
      (GUD)], such as syphilis, chancroid and genital herpes, in New York City between
      1990 and 1992. DESIGN: Unlinked HIV-1 serosurvey using remnant serum drawn
      originally for routine syphilis screening. SETTING AND PATIENTS: Consecutive
      sample of patients presenting to New York City Department of Health STD clinics
      for STD examination (n = 41,678). MAIN OUTCOME MEASURE: Serologic evidence of
      antibody to HIV-1. RESULTS: Although overall HIV seroprevalence and GUD incidence
      declined between 1990 and 1992, seroprevalence in patients with GUD increased
      from 10 to 16%. In contrast, seroprevalence in patients with non-ulcerative STD
      decreased. The most dramatic changes in seroprevalence associated with GUD
      occurred in patients using crack cocaine and injecting drugs. CONCLUSIONS:
      Despite declining HIV seroprevalence and GUD incidence, the association between
      GUD and HIV infection has strengthened over time in New York City STD clinics.
      Longitudinal incidence studies are needed to elucidate the biological, behavioral
      and temporal associations between GUD and HIV. Timely diagnosis and treatment of
      acute STD and more intensive risk reduction strategies at the clinics and
      associated testing sites, with a particular focus on GUD patients, are indicated.

PMID- 7718190
TI  - Imprisonment: a risk factor for HIV infection counteracting education and
      prevention programmes for intravenous drug users.
AB  - OBJECTIVES: To examine changes of risk behaviour and its determinants as well as
      risk factors for HIV infection in intravenous drug users (IVDU) with particular
      attention to imprisonment and its risk patterns. SETTING: In 1993 a multisite
      cross-sectional study was carried out by standardized questionnaires and
      blood/saliva samples in which 612 IVDU from Berlin were enrolled. RESULTS:
      Multifactorial analysis revealed that the most important risk factor for HIV
      infection was needle-sharing in prison. In total, 353 IVDU (58%) reported reduced
      risk behaviour; changes related more to injection behaviour than sexual practices
      (91 versus 68%). Important determinants for needle-sharing during the last 6
      months were intravenous drug use in prison, duration of drug-taking history, and
      knowledge of a negative HIV test. The most frequently reported reasons for
      current needle-sharing were having shared needles with only one regular partner
      (45%) and imprisonment (26%). CONCLUSION: Information campaigns and other
      prevention measures appear to have produced risk awareness in IVDU, and as a
      consequence, a reduction in risk behaviour. The situation in prisons (no sterile
      injecting equipment, no effective disinfectants), however, is counteractive to
      prevention measures implemented outside prisons. An important task for future
      strategies should be to enable IVDU to avoid HIV transmission while in prisons.

PMID- 7718191
TI  - HIV prevalence and risk factors in university students.
AB  - OBJECTIVE: To estimate HIV prevalence and risks in university students. DESIGN:
      Anonymous self-completion questionnaire and HIV survey with saliva samples.
      SETTING: University students at matriculation. PARTICIPANTS: All first and third
      year undergraduates and newly registering postgraduates at the University of
      Edinburgh, Scotland. MAIN OUTCOME MEASURES: HIV prevalence, sexual behaviour,
      condom use, drug use. RESULTS: The questionnaire responses were used to classify
      the 4665 respondents into four groups, ordered by risk of HIV positivity, and a
      sample of 2041 was selected for testing. All of the top two risk groups were
      tested (217 and 758 tests, respectively) as well as a random sample of the
      others. Five positive HIV-antibody tests were detected, all from the highest risk
      group. This gives an estimated rate of 1.2 per 1000 (95% confidence interval, 0.4
      2.9) for all respondents. Only one of the five HIV-positives had been tested for
      HIV. The factors associated with HIV positivity were residence in Africa,
      intravenous drug use and male homosexuality. Overall, 74% of respondents reported
      ever having had sexual intercourse and this rate was the same for men and women.
      Reported intravenous drug use was very low: 0.5% for men and 0.1% for women.
      Condom use was more common for partners of short acquaintance, but unrelated to
      the number of sexual partners in the last year. CONCLUSIONS: There was no
      evidence of the spread of HIV infection beyond known high-risk groups in this
      population. This may be a result of relatively low levels of HIV risk-taking
      behaviour in the majority of respondents.

PMID- 7718192
TI  - Reduced frequency of percutaneous injuries in surgeons: 1993 versus 1988.
AB  - OBJECTIVE: To compare the frequency of occupational injuries reported by surgeons
      in 1993 with similar data obtained in 1988. DESIGN AND SETTING: Two point
      prevalence studies of percutaneous injuries of surgeons practicing in tertiary
      and non-tertiary-care hospitals in the New York metropolitan area. PARTICIPANTS:
      A total of 202 surgeons and surgical residents surveyed in 1988 and 347 surveyed
      in 1993 (67 and 65% of the eligible groups, respectively), including 85 surgeons
      in 1993 (71% of the eligible group) who had participated in the 1988 survey.
      OUTCOME MEASURES: Yearly frequency of percutaneous injuries, and injury frequency
      per 1000 operative hours. RESULTS: There was a significant decrease in the
      frequency of reported percutaneous injuries over the 5-year period. For all
      surgeons, the mean number of yearly injuries decreased from 5.5 +/- 14.4 SD to
      2.1 +/- 6.0 SD (P < or = 0.001). Paired analysis of the subgroup of 85 surgeons
      who participated in both surveys showed a nearly identical decrease (P = 0.001).
      Significant decreases were observed in general surgeons, specialists and
      residents. CONCLUSIONS: During the 5 years studied, surgeons practicing in the
      greater New York metropolitan area reported a significant reduction in the
      frequency of occupationally associated percutaneous injuries. The reduced risk of
      percutaneous injuries should substantially lower the rate of acquired infections
      from blood-borne pathogens.

PMID- 7718193
TI  - T lymphocytes with gamma/delta T-cell receptors in patients with AIDS and
      Pneumocystis carinii pneumonia.

PMID- 7718194
TI  - Zidovudine to decrease mother-to-child transmission of HIV-1: is it good for
      developing countries?

PMID- 7718195
TI  - Kaposi's sarcoma involving bone in a patient with AIDS.

PMID- 7718196
TI  - Octreotide therapy in AIDS-related, refractory diarrhea: results of a multicentre
      Canadian-European study. Octreotide International Multicentre AIDS-Diarrhea
      Study.

PMID- 7718197
TI  - The European-Australian Collaborative Group Study 017 of zidovudine versus
      placebo.

PMID- 7718198
TI  - HIV risk behaviour among injecting drug users in Warsaw.

PMID- 7718199
TI  - Prostitution and HIV.

PMID- 7718200
TI  - Drug-resistant Mycobacterium tuberculosis strains in tuberculosis inpatients in
      Bangui, Central African Republic.

PMID- 7718201
TI  - Pathogenicity of the microsporidia.

PMID- 7718202
TI  - Diabetes mellitus following treatment of AIDS with didanosine.

PMID- 7718203
TI  - Atypical pneumonias in children.
AB  - The major agents responsible for atypical pneumonia in children include a wide
      variety of organisms, one Mycoplasma species, two Chlamydia species, a
      rickettsia, and one fastidious bacterium. Mycoplasma pneumoniae and C. pneumoniae
      together may be responsible for over 40% of these infections. Recognition of the
      role that these agents play in pneumonia is important since many of the
      diagnostic methods used to detect these organisms are not available in most
      hospital microbiology laboratories. If you don't look, you won't find.
      Epidemiologic factors can provide valuable clues, especially with the less
      frequently encountered infections, since it is almost impossible to make a
      clinical diagnosis on which to base treatment. A reliable history of avian
      exposure should suggest psittacosis, exposure to sheep or pregnant cats suggests
      Q fever, and children with underlying malignancy or immunodeficiency or those
      receiving systemic steroids may have legionnaires' disease. None of these
      organisms are susceptible to beta-lactam antibiotics. Sometimes the diagnosis is
      not considered until after the child has failed to respond to a penicillin or a
      cephalosporin and routine bacteriology is negative. In view of the role played by
      M. pneumoniae and C. pneumoniae, a macrolide may be the first-line antibiotic for
      atypical pneumonia in children.

PMID- 7718204
TI  - Influenza virus infection in children.

PMID- 7718205
TI  - Hepatitis E.

PMID- 7718206
TI  - Adjuvant therapy in meningitis.

PMID- 7718207
TI  - An update on pediatric immunization.

PMID- 7718208
TI  - Use of prophylactic antibiotics in children.

PMID- 7718209
TI  - Control of sexually transmitted diseases in adolescents: the clinician's role.
AB  - Sexually transmitted diseases common in the adolescent population are associated
      with significant acute morbidity, complications, and long-term sequelae.
      Clinicians have the opportunity to play a unique and important role in the
      control of STD rates among adolescents. Not only are clinicians in a position to
      routinely discuss healthy sexual development, decision making, and primary STD
      prevention, they are also in a position to effectively diagnose and manage STDs
      among both asymptomatic and symptomatic adolescents. Addressing issues related to
      sexuality and STDs in a consistent and repetitive manner during routine visits
      will likely increase physician proficiency in this important area of clinical
      care of adolescents, as well as increase adolescents' recognition of the
      clinician as a valuable resource.

PMID- 7718210
TI  - Antibiotic allergy in children.

PMID- 7718211
TI  - Intravenous catheter-related infections.
AB  - Vascular catheter-related infection is an important cause of mortality and
      morbidity in hospitalized patients. The mean incidence of catheter-related
      bloodstream infection in hospitalized pediatric patients is 2.4 episodes per
      1,000 days. Totally implantable central venous catheters may be associated with a
      lower risk of infection. Coagulase-negative staphylococci are the predominant
      cause and account for about one third of episodes of catheter-related bloodstream
      infection. The diagnosis of catheter-related bloodstream infection is often
      difficult because there are frequently no signs of inflammation around the
      catheter. Diagnosis depends on either a positive quantitative catheter culture
      yielding the same microorganism recovered from the bloodstream or differential
      quantitative blood cultures with significantly greater colony counts from blood
      drawn through the catheter than from blood drawn through a peripheral vein.
      Alternatively, probably catheter-related sepsis can be diagnosed when clinical
      sepsis is refractory to antimicrobial therapy but responds to catheter removal.
      Often these criteria are not met but catheter-related bloodstream infection is
      presumed because a common skin microorganism is isolated from the blood when
      clinical manifestations of bloodstream infection are present and there is no
      other apparent source of infection. Microorganisms causing catheter-related
      bloodstream infection gain access to the bloodstream predominantly from either
      the catheter insertion site or the catheter hub. Most catheter-related infections
      occurring shortly after catheter insertion probably gain access to the
      bloodstream by extraluminal migration along the catheter from the skin at the
      catheter insertion site. When catheters are in place for extended periods,
      especially greater than 30 days, the catheter hub probably plays a major role in
      microorganisms gaining access and then migrating endoluminally until reaching the
      bloodstream. Recently employed strategies for the prevention of catheter-related
      infections include topical antibiotics or antiseptics at the catheter insertion
      site, flush solutions containing vancomycin, and bonding antimicrobial agents to
      the catheter. Infection of peripheral and central venous catheters generally
      resolves after catheter removal. For tunneled silicone catheters, most episodes
      of catheter-related infection can be initially managed with antimicrobial therapy
      infused through the catheter without catheter removal. Staphylococcus aureus is
      generally more aggressive and associated with more complications than coagulase
      negative staphylococci. Microorganisms that usually require catheter removal
      include Candida and Bacillus species. Adjunctive treatments of catheter
      infections include the use of urokinase. Catheter-related infection remains an
      important complication of vascular access. Novel prevention and treatment
      strategies are currently being investigated. In the near future bonding of
      antibiotics or other agents to catheters may become routine.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7718212
TI  - Superantigens and their role in infectious disease.
AB  - Although the exact mechanisms by which superantigens may contribute to the
      pathogenesis of diseases are unknown, it seems increasingly likely that they have
      a role in the induction and pathogenesis of disease. The studies described here
      demonstrate that in several different diseases either bacterial or viral
      superantigens can be isolated from patients. There is also a preferential
      expansion of particular V beta T-cell subsets, which is a common feature of
      superantigen stimulation. From the work that has been done to date it can be
      hypothesized that superantigens may act in several ways. They may stimulate and
      activate T cells that are autoreactive and lead to the induction or exacerbation
      of autoimmune disease, as in RA. Alternatively, they may lead to the depletion of
      T-cell subsets based on V beta expression, thereby resulting in the severe
      reduction in lymphocytes in certain immunodeficiency diseases such as AIDS. But
      perhaps the most likely contribution of superantigens to disease pathogenesis is
      seen indirectly by their effect on the immune system-particularly the stimulation
      of large numbers of T lymphocytes expressing the same V beta domain. Thus it is
      likely that the direct effect of various T-cell-derived inflammatory mediators
      (i.e., interleukins and other cytokines) released by these activated T
      lymphocytes is the primary cause of disease pathology via response to
      superantigen stimulation. In addition to the diseases discussed here, there are a
      number of other diseases in which a potential role for superantigens is being
      studied. These include autoimmune diseases seen after group A streptococcal
      infections in which the streptococcal M protein has been postulated to act as a
      superantigen such as scarlet fever, rheumatic heart disease, and
      poststreptococcal glomerulonephritis. Other diseases being studied include
      psoriasis, lupus-like disease, and lymphoproliferative diseases (reviewed in
      Kotzin et al.). In the coming years the exact role of superantigens and the
      specific mechanisms by which they contribute to disease should be more clearly
      defined. Our understanding of these molecules could also lead to new therapies
      for the treatment of these diseases.

PMID- 7718213
TI  - Brain abscess and other intracranial suppurative complications.

PMID- 7718214
TI  - Botulism.

PMID- 7718215
TI  - Varicella-zoster virus: prospects for control.
AB  - There have been a number of new developments in the field of VZV concerning
      pathogenesis, diagnosis, prevention, and treatment. These include improved
      understanding of how latent infection develops and is maintained, the development
      and, we hope, licensure of live attenuated varicella vaccine for routine use in
      children and in adults who have not had varicella, an increased availability of
      antiviral therapy for healthy and immunocompromised patients, and the development
      of newer diagnostic techniques, including PCR to diagnose illnesses caused by VZV
      and LA for rapid, sensitive, and accurate determination of immune status to VZV.
      Even as vaccine use becomes more and more widespread, we will continue to need
      effective antiviral therapy for VZV for use in immunocompromised persons and in
      those in whom zoster develops. Eventually it may be possible to develop either a
      vaccine or an antiviral drug that prevents the development of latent VZV
      infection. Until that time, however, VZV will remain with us, and we will
      continue to need an effective antiviral armamentarium, including diagnostic
      techniques, passive immunization, antiviral therapy, and vaccine.

PMID- 7718216
TI  - Current considerations in the etiology and diagnosis of tympanosclerosis.
AB  - Current concepts of formation of tympanosclerosis in the middle ear are reviewed,
      as are various clinical considerations. Ultrastructural changes are discussed. A
      differential diagnosis includes disorders affecting middle ear sound conduction,
      with the most prevalent involving otosclerosis and cholesteatoma.

PMID- 7718218
TI  - Vascular permeability to sodium fluorescein in the rabbit cranial nerve root:
      possible correlation with normal cranial nerve enhancement on gadolinium-enhanced
      magnetic resonance imaging.
AB  - Vascular permeability in cranial nerve roots was examined after intravenous
      injection of sodium fluorescein in the adult rabbit. Fluorescence was observed in
      the distal nerves through the following portions: intracavernous portion of the
      oculomotor nerve, distal internal auditory canal segment of the facial nerve, and
      ganglionic portions of the trigeminal, glossopharyngeal and vagus nerves. In the
      acoustic nerve, the vestibular ganglion showed fluorescence. No fluorescence was
      observed in the olfactory or optic nerves. During in vivo gadolinium-enhanced
      magnetic resonance imaging (Gd-MRI) of two separate animals, trigeminal nerve
      enhancement was observed in the region showing fluorescence. Histologically,
      intense fluorescence was observed in ganglia and external nerve sheaths of the
      cranial nerves showing macroscopic fluorescence. A slight fluorescence was also
      seen in endoneurial connective tissue but not observed within the nerve fibers.
      The results of this study suggest that the physiological enhancement of human
      cranial nerves seen on Gd-MRI may correlate with vascular permeability.

PMID- 7718219
TI  - Neuroendocrine carcinoma of the ethmoid sinus.
AB  - The paranasal sinuses are a rare site for neuroendocrine carcinoma (NEC). In
      contrast to the other regions, NEC of the sinuses has been reported to be
      recurrent and locally destructive. We report a case of NEC of the ethmoid
      sinuses. The patient was a 16-year-old Indian boy and was treated with radiation
      therapy to 6500 rad. He has been disease free for the past 5 years. All the cases
      reported to date were also reviewed.

PMID- 7718217
TI  - Analysis of T-cell receptor expressing lymphocytes infiltrating squamous cell
      carcinomas of the upper aerodigestive tract.
AB  - T-lymphocytes expressing T-cell receptors (TCRs) of the gamma/delta type have
      been suggested to play an important role in mucosal defense against infection and
      neoplastic transformation. In this study, an immunohistochemical investigation
      was performed on the distribution of alpha/beta and gamma/delta TCRs among tumor
      infiltrating lymphocytes. Thirteen patients with squamous cell carcinomas of the
      upper aerodigestive tract were studied, using monoclonal antibodies and an avidin
      biotin-peroxidase technique. Most of the T-cells had an alpha/beta TCR. Only 1.6%
      of the T-cells within the cancer tissue and 1.2% of the T-cells in the parenchyma
      adjacent to the cancer tissue expressed gamma/delta TCRs. These results are
      consistent with the results of similar studies in bronchial and breast
      carcinomas. Biopsies from normal oral mucosa in nine healthy individuals showed
      that 1.3% of the T-cells within the epithelium and 1.0% of those in the lamina
      propria adjacent to the epithelium expressed gamma/delta TCRs. Quantitatively the
      results do not support the theory that gamma/delta T-cells play an important role
      in the immunological response against cancer tissue in the mucosa of the upper
      aerodigestive tract. The functional role of these cells in the mucosa and in
      response to carcinomas is, however, still uncertain.

PMID- 7718220
TI  - Modulation of cochlear responses in the guinea pig by low-frequency, phase
      shifted maskers following noise trauma.
AB  - Low-frequency acoustic biasing using an intensive phase-shifted, low-frequency
      masker was studied according to its ability to determine disorders of cochlear
      micromechanics following noise trauma in the guinea pig as animal model.
      Statistical analyses proved that this technique allowed electrophysiological
      differentiation of controls versus groups with different degrees of
      experimentally induced threshold shifts. To substantiate group differences an
      intensity of at least 70 dB SPL was required for the 52 Hz masker and the
      difference in relation to the test-tone intensity had to be +/- 10 or +/- 20 dB
      SPL. The noise-traumatized cochlea could be identified by means of a threshold
      shift for the 5 microV pseudothreshold, a low modulation span of the compound
      action potential amplitude (< 25-50 microV frequency dependent), and reduced
      positive summating potential amplitude with negative non-modulating values within
      the different measurement phases for 1 and 2 kHz stimulation.

PMID- 7718221
TI  - Surgical treatment of tympanosclerosis.
AB  - Tympanosclerosis as a cause of conductive hearing loss may require corrective
      surgery in carefully selected cases, although results of treatment have been
      controversial and must be viewed with caution. Currently available surgical
      techniques are reviewed and outcomes discussed.

PMID- 7718222
TI  - Continuous pressure measurements during sleep to localize obstructions in the
      upper airways in heavy snorers and patients with obstructive sleep apnea
      syndrome.
AB  - Twenty-one patients were examined, of whom 18 suffered from obstructive sleep
      apnea syndrome and 3 were heavy snorers. The diagnosis was established by a
      combination of medical history, clinical examination and standard nocturnal
      polysomnography. Five pressure transducers were used in the pharynx and one in
      the esophagus, in addition to monitors for oxygen saturation and oro-nasal
      airflow. A clinically significant obstruction was defined as occurring when the
      pressure difference between two transducers was higher than 50% of the more
      caudal of the two pressures. In the 20 patients having obstructions during sleep,
      7 had obstruction in only one segment of the airway, 9 in two segments and 4 in
      three segments. All but 2 patients had obstructions in the velopharyngeal region.
      Since the effect of uvulopalatopharyngoplasty (UPPP) is best during the first few
      months after surgery, 10 patients were re-examined after only 3 months in order
      to record optimal results sequentially. Of these, 6 still had obstructions
      involving the velopalatine segments and only 4 had none. This may explain why
      UPPP has a success rate of only 50-70% in most publications, depending on the
      definitions of success.

PMID- 7718223
TI  - Electromotile responses and frequency tuning of isolated outer hair cells of the
      guinea pig cochlea.
AB  - Isolated outer hair cells (OHC) of the guinea pig cochlea were exposed to
      external alternating electric fields parallel to the longitudinal axis of the
      cells. This resulted in oscillations of the cells' length that were measured
      photoelectrically using a ratiometric light amplifier. At 5 Hz and elongations up
      to 300 nm, amplitude of the cell length during oscillation was a linear function
      of the amplitude of the sinusoidal electric field. When increasing the stimulus
      frequency up to 32 kHz, OHC length changes followed the stimulus cycle-by-cycle.
      Oscillations at frequencies above 32 kHz escaped the experimental approach by
      their small amplitudes and could not be excluded. The frequency dependence of the
      motile response measured at 5-12,000 Hz had low-pass filter characteristics in
      cells of the second, third and fourth turns of the cochlea. However, frequency
      tuning of the motile response was absent in each OHC and systematic differences
      between different turns were not observed.

PMID- 7718224
TI  - The various shapes of the paries jugularis and the frequency of additional ducts
      in the fossa jugularis as further factors influencing the spread of pathological
      processes.
AB  - We investigated 100 skulls and found in 8 cases a dehiscence of the paries
      jugularis. In 7 cases this was on the left side and in 1 case on the right.
      Thickness of the paries jugularis was estimated by means of a diaphanoscopic
      technique. We classified data according to four degrees of diaphaneity: 0 (hardly
      translucent), 1 (translucent), 2 (brightly translucent) and 3 (nearly
      transparent). The frequencies of these degrees were: 0, 38 cases (19%); 1, 122
      cases (61%); 2, 35 cases (17.5%); and 3, 5 cases (2.5%). In investigating the
      frequency of additional ducts in the paries jugularis, we distinguished between
      three types of solum tympani: type I, no additional canals (18 cases); type II, 1
      10 additional canals (172 cases); and type III, more than 10 additional canals
      (10 cases).

PMID- 7718225
TI  - Determination of viability of cryopreserved cartilage grafts.
AB  - Although transplantation of preserved cartilage has assumed a role of great
      importance in reconstructive surgery, there are many divergent and contradictory
      opinions with regard to the outcome of cryopreserved cartilage. This study was
      formulated to assess the functional state of chondrocytes after cryopreservation.
      Freeze injury and survival were studied using the trypan blue dye exclusion test,
      functional assay for cell adhesion and transmission electron microscopy. The
      methods applied clearly proved that a greater part of the cartilage cells was
      irreversibly damaged by cryopreservation. Findings demonstrated that
      cryopreserved cartilage remained non-viable and was not able to originate new
      cartilage. Thus, such cartilage will be subject to resorption processes and not
      practical for reconstruction of parts of the skeleton subject to mechanical
      stress. The feasibility of cryopreservation techniques for providing vital
      cartilage substitutes needs further evaluation.

PMID- 7718226
TI  - Effects of human middle ear effusions on the mucociliary system of the
      tubotympanum in the guinea pig.
AB  - Effusion fluid resulting from otitis media contains a variety of inflammatory
      substances. This middle ear effusion (MEE) may be itself affect the mucosa of the
      tubotympanum and contribute to chronicity of the condition. The present study was
      designed to elucidate in vitro and in vivo effects of MEEs on the mucosa of the
      guinea pig tubotympanum. The results obtained demonstrated that the ciliary
      activity of the eustachian tube was reduced in the presence of human MEEs. This
      activity decreased to approximately 80% in the presence of serous MEE at 48 h and
      was 60% after exposure to mucoid MEE. Intratympanic inoculation of human MEEs
      resulted in accumulation of a serous effusion in the tympanic cavity. Histologic
      study of the tubotympanum in inoculated animals demonstrated mucociliary
      dysfunction as well as a general inflammatory process and increased vascular
      permeability. This damage was more prominent following inoculation with the
      mucoid MEEs. The ciliary depression and inflammation found in the tubotympanum
      suggest that the pathologic nature of MEEs may be, at least partially,
      responsible for the chronicity of otitis media.

PMID- 7718227
TI  - Olfactory disturbances caused by the anti-cancer drug tegafur.
AB  - Olfactory disturbances induced by the anti-cancer drug tegafur were studied in
      separate clinical and experimental investigations. Five patients with olfactory
      dysfunction after tegafur were studied and were found to have normal endoscopic
      findings of the olfactory cleft mucosa. The average period for drug
      administration was 22 months. Recovery from the olfactory disturbance was poor
      and biopsy of the olfactory mucosa revealed severely degenerated epithelium. In
      experimental studies in a guinea pig animal model, effects of oral tegafur on
      mitotic cells in the olfactory epithelium were examined using bromodeoxyuridine
      (BrdU) uptake as index. At the conclusion of 3 weeks' treatment, no pronounced
      morphological changes were seen, but the number of BrdU-incorporating cells
      decreased in proportion to the dose of tegafur used. Following long-term
      administration of tegafur 18 months, mitotic cells reacting to BrdU or
      proliferating cell nuclear antigen had virtually disappeared, indicating
      persistent inhibition of mitotic cell activity. Morphological changes present
      included decreased olfactory cell numbers, loss of cells in areas just above
      basal cells and degeneration of the mucous layer.

PMID- 7718228
TI  - Unusual presentation of a first branchial cleft.
AB  - An atypical case of a first branchial cleft presenting with a cutaneous fistula
      and an epidermoid cyst of the external auditory canal is reported. The relevant
      embryology of the branchial apparatus is summarized, and variations of first
      branchial anomalies are discussed. The relationship with a congenital
      cholesteatoma is discussed.

PMID- 7718229
TI  - Accessory nose associated with unilateral incomplete cleft lip.
AB  - We describe a 6-month-old Turkish girl who was found to have a mass near her nose
      at birth and incomplete cleft lip. No other clinical and radiological
      abnormalities were demonstrable elsewhere in her body. Histological examination
      of the excised mass showed an organoid structure that was consistent with an
      accessory nose.

PMID- 7718230
TI  - Infection of frog neurons with vaccinia virus permits in vivo expression of
      foreign proteins.
AB  - Vaccinia virus can be used to infect cells in the CNS of frogs, Xenopus laevis,
      and Rana pipiens, both in vivo and in vitro. In vivo infections were accomplished
      by injection of viral solution into the tectal ventricle of stage 40-48 tadpoles
      or by local injections into distinct neural regions. Infections with high titer
      of virus injected into the ventricle resulted in the majority of cells in the
      brain expressing foreign protein, while cells in the retina and optic nerve
      showed no expression. Infection with lower viral titers resulted in fewer
      infected cells that were distributed throughout the otherwise normal tissue.
      Intense expression of foreign protein in the brain was observed 36 hr after
      injection and remained high for at least 4 days. Infected animals developed
      normally and had the same number of cells in the optic tectum as control animals.
      Infection with a recombinant virus carrying the gene for Green Fluorescent
      Protein labels neurons, so that infected cells can be observed in vivo. Vaccinia
      virus provides a versatile means to alter proteins in distinct populations of
      neurons in amphibia.

PMID- 7718231
TI  - Vaccinia virus transfection of hippocampal slice neurons.
AB  - Here we describe a technique that uses a recombinant vaccinia virus to transfect
      neurons in rat hippocampal slices. This technique allows the use of molecular
      biological manipulations on neuronal tissue while maintaining intact synaptic
      function. This method should be useful in testing specific hypotheses regarding
      the role of synaptic proteins.

PMID- 7718232
TI  - From vesicle docking to endocytosis: intermediate reactions of exocytosis.

PMID- 7718233
TI  - Individual neurons dissociated from rat suprachiasmatic nucleus express
      independently phased circadian firing rhythms.
AB  - Within the mammalian hypothalamus, the suprachiasmatic nucleus (SCN) contains a
      circadian clock for timing of diverse neuronal, endocrine, and behavioral
      rhythms. By culturing cells from neonatal rat SCN on fixed microelectrode arrays,
      we have been able to record spontaneous action potentials from individual SCN
      neurons for days or weeks, revealing prominent circadian rhythms in firing rate.
      Despite abundant functional synapses, circadian rhythms expressed by neurons in
      the same culture are not synchronized. After reversible blockade of neuronal
      firing lasting 2.5 days, circadian firing rhythms re-emerge with unaltered
      phases. These data suggest that the SCN contains a large population of
      autonomous, single-cell circadian oscillators, and that synapses formed in vitro
      are neither necessary for operation of these oscillators nor sufficient for
      synchronizing them.

PMID- 7718234
TI  - Targeted neuronal cell ablation in the Drosophila embryo: pathfinding by follower
      growth cones in the absence of pioneers.
AB  - We developed a rapid method that uses diphtheria toxin, the flp recognition
      target sequences, and the GAL4-UAS activation system, to ablate specific neurons
      in the Drosophila embryo and to examine the consequences in large numbers of
      embryos at many time points. We used this method to show that, in the absence of
      the aCC axon, which pioneers the intersegmental nerve in the PNS, the three U
      follower axons are delayed and make frequent errors. However, the pathway
      ultimately forms in most segments. We also ablated the axons that pioneer the
      first longitudinal pathways within the CNS and observed similar results; the
      formation of longitudinal pathways is delayed and disorganized in 70% of
      segments, but these tracts ultimately form in 80% of segments. Thus, pioneers
      facilitate the development of PNS and CNS axon pathways; in their absence,
      followers are delayed and make numerous errors. However, pioneers are not
      absolutely required, as these embryos display a remarkable ability to correct for
      the loss of the pioneering neurons.

PMID- 7718235
TI  - Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss
      of hippocampal granule and striatal parvalbumin-containing neurons.
AB  - Homozygous Igf1-/- mice at 2 months of age had reduced brain weights, with
      reductions evenly affecting all major brain areas. The gross morphology of the
      CNS was normal, but the size of white matter structures in brain and spinal cord
      was strongly reduced, owing to decreased numbers of axons and oligodendrocytes.
      Myelinated axons were more strongly reduced in number than unmyelinated axons.
      The volume of the dentate gyrus granule cell layer was reduced in excess of the
      decrease in brain weight. Among populations of calcium-binding protein-containing
      neurons, there was a selective reduction in the number of striatal parvalbumin
      containing cells. Numbers of mesencephalic dopaminergic neurons, striatal and
      basal forebrain cholinergic neurons, and spinal cord motoneurons were unaffected.
      Cerebellar morphology was unaltered. Our findings suggest cell type- and region
      specific functions for IGF-I and emphasize prominent roles in axon growth and
      maturation in CNS myelination.

PMID- 7718236
TI  - Evidence for an important role of IGF-I and IGF-II for the early development of
      chick sympathetic neurons.
AB  - The ability of immature neurons from chick lumbosacral sympathetic ganglia to
      proliferate in vitro was used to identify factors that affect neurogenesis. Under
      serum-free culture conditions, insulin-like growth factor I (IGF-I), IGF-II, or
      insulin caused an increase in the proportion of cells that incorporated
      [3H]thymidine. In addition, IGFs also stimulated neurite outgrowth from these
      immature sympathetic neurons. IGF-I and IGF-II mRNA was found to be expressed in
      E7 sympathetic ganglia during the period of neurogenesis. IGF-I was detectable in
      fibroblasts, whereas IGF-II mRNA was expressed by neurons, glia, and fibroblasts.
      Elimination of endogenous IGFs by neutralizing antibodies resulted in a reduction
      of neuron proliferation and neuron number, whereas elevation of IGF levels by
      treatment with IGF-I increased sympathetic neuron proliferation in vivo. These
      findings suggest an important role of IGFs for the development of sympathetic
      neurons and imply a general role of IGFs in the control of neurogenesis and
      neurite outgrowth.

PMID- 7718237
TI  - Role for a synapse-specific carbohydrate in agrin-induced clustering of
      acetylcholine receptors.
AB  - Lectins such as VVA-B4, which bind N-acetylgalactosaminyl (GalNAc)-terminated
      saccharides, selectively stain the neuromuscular junction, thus defining a
      synapse-specific carbohydrate. In seeking roles for this carbohydrate, we asked
      whether VVA-B4 affected the distribution of acetylcholine receptors (AChRs) on
      cultured muscle cells. We found that incubation of myotubes with VVA-B4 induced
      formation of AChR clusters and potentiated the effect of a nerve-derived
      clustering factor, agrin. Additional experiments implicated GalNAc-terminated
      glycoconjugates as modulators of agrin-induced AChR clustering. Enzymatic removal
      of GalNAc residues or treatment with a multivalent protein-GalNAc conjugate
      blocked agrin-induced clustering, whereas enzymatic unmasking of additional
      GalNAc residues induced clustering in the absence of added agrin. Moreover,
      incubation with agrin led to redistribution of VVA-B4-binding material on
      myotubes. Together, these results suggest that agrin-induced clustering of AChRs
      involves a GalNAc-dependent step.

PMID- 7718238
TI  - Glutamate receptor antibodies activate a subset of receptors and reveal an
      agonist binding site.
AB  - Two rabbits immunized with a portion of glutamate receptor (GluR) subunit GluR3
      (amino acids 245-457) exhibited seizure-like behaviors, suggesting that
      antibodies to GluR3 may modulate neuronal excitability. Using whole-cell
      recording, rabbit GluR3 antisera were tested on cultured fetal mouse cortical
      neurons. In a subset of kainate-responsive neurons, miniperfusion of antisera and
      IgG evoked currents that were blocked by CNQX. Immunoreactivity to synthetic
      peptides prepared to subregions GluR3A (amino acids 245-274) and GluR3B (amino
      acids 372-395) was present in both rabbit sera. Peptide GluR3B, but not GluR3A,
      specifically blocked antisera- and IgG-evoked currents. Similar receptor
      activation and anti-GluR3 reactivity was present in sera from patients with
      active Rasmussen's encephalitis, an intractable pediatric epilepsy. Thus,
      antibodies to GluR3 define a region involved in agonist binding and specific
      receptor activation. These data suggest that antibodies to neuronal receptors can
      function as agonists and that autoantibodies to GluRs may be highly specific
      neurotoxicants in some neurological diseases.

PMID- 7718239
TI  - Measurements of exocytosis from single presynaptic nerve terminals reveal
      heterogeneous inhibition by Ca(2+)-channel blockers.
AB  - The effect of various Ca(2+)-channel blockers on exocytosis has been studied at
      the level of single presynaptic terminals in rat hippocampal cell cultures. The
      fluorescence change of the styryl dye FM 1-43 has been used as a measure of
      exocytosis during electrical stimulation. omega-Conotoxin GVIA (2-10 microM)
      completely inhibited exocytosis in approximately 45% of the boutons in the field
      of view, while in approximately 55% exocytosis was inhibited incompletely (by
      38%). This heterogeneity in response of presynaptic boutons was not seen with
      isradipine (5 microM) or omega-agatoxin IVA (80 nM), which inhibited exocytosis
      by 23% and 17%, respectively. However, it was observed with a combination of all
      three blockers. Pre- and postsynaptic events could be separated in single
      synapses by measuring FM1-43 release and NMDA-induced changes in the
      intracellular Ca2+ concentration independently.

PMID- 7718240
TI  - The cellular Na+ pump as a site of action for carbon monoxide and glutamate: a
      mechanism for long-term modulation of cellular activity.
AB  - Carbon monoxide (CO) induces a long-lasting alteration in cerebellar alpha 3-Na,K
      ATPase independent of [Na+] but linked to cGMP synthesis and localized to
      Purkinje neurons. The action of CO is absent in Purkinje neuron-deficient mice,
      mimicked by 8-Br-cGMP, and blocked by inhibition of PKG. Glutamate (Glu) and
      metabotropic agonists mimic the action of CO, an effect that requires PKC and is
      associated with CO synthesis. These data suggest that CO regulates Na,K-ATPase
      through cGMP and PKG, and that Glu regulates CO through mGluRs. This system is
      also modulated by NMDA agonists and nitric oxide, possibly via Glu release, as
      well as by free radicals. These findings offer a mechanism by which CO, Glu, and
      free radicals can exert specific effects on synaptic transmission (relevant to
      long-term changes in cell excitability), as well as more general actions on
      energy metabolism (relevant to the pathophysiology of excitotoxicity).

PMID- 7718241
TI  - Facilitation and depression at single central synapses.
AB  - Using whole-cell recording from CA1 hippocampal pyramidal neurons and minimal
      stimulation of Schaffer collaterals, we have studied what seem to be single
      synapses. Although the transmission at a putative single synapses is quite
      unreliable, the synapse can be made to release transmitter reliably in response
      to the second stimulus in a pair of stimuli that re presented in rapid succession
      (e.g., 50 ms separation). Statistical analysis of transsmision failures seen with
      such paired pulse stimulation reveals that the majority of stimulus-evoked
      synaptic currents (> 90%) are produced by a single synapse under the conditions
      of minimal stimulation, even if multiple synapses are actually present.
      Individual synapses appear to release either zero or one quantum; that is, a
      single synapse seems to have only one functional release sit at any time. After
      the release site has been used, approximately 20 ms is required to refill the
      site so that it can be used again.

PMID- 7718242
TI  - Odorant-specific adaptation pathways generate olfactory plasticity in C. elegans.
AB  - Following prolonged exposure to an odorant, C. elegans exhibits a diminished
      response to the odorant for several hours. This olfactory adaptation is odorant
      selective; animals can adapt independently to different odorants sensed by a
      single pair of olfactory neurons, the AWC neurons. The mechanism of olfactory
      adaptation is genetically complex, with different genes required for adaptation
      to different odorants. Animals mutant for the gene adp-1 fail to adapt to a
      subset of AWC-sensed odorants; adp-1 affects a calcium-dependent process required
      for adaptation. Mutations in another gene, osm-9, affect adaptation to a
      different but overlapping subset of AWC-sensed odorants. Mutations in adp-1 and
      osm-9 do not diminish the ability of unadapted animals to respond to odorants,
      indicating that odorant sensation and odorant adaptation are distinct processes.

PMID- 7718244
TI  - Mapping the binding-site crevice of the dopamine D2 receptor by the substituted
      cysteine accessibility method.
AB  - The binding site of the dopamine D2 receptor, like that of other homologous G
      protein-coupled receptors, is contained within a water-accessible crevice formed
      among its seven membrane-spanning segments. We have developed a method to map
      systematically all the residues forming the surface of this binding-site crevice,
      and we have applied this method to the third membrane-spanning segment (M3). We
      mutated, one at a time, 23 residues in and flanking M3 to cysteine and expressed
      the mutant receptors heterologously. Ten of these mutants reacted with charged,
      hydrophilic, lipophobic, sulfhydryl-specific reagents, added extracellularly, and
      were protected from reaction by a reversible dopamine antagonist. Thus, the side
      chains of these residues are exposed in the binding-site crevice, which like M3
      extends from the extracellular to the intracellular side of the membrane. The
      pattern of exposure is consistent with a short loop followed by six turns of an
      alpha helix.

PMID- 7718243
TI  - Neuronal adaptation to amphetamine and dopamine: molecular mechanisms of
      prodynorphin gene regulation in rat striatum.
AB  - Induction of prodynorphin gene expression by psychostimulant drugs may represent
      a compensatory adaptation to excessive dopamine stimulation and may contribute to
      the aversive aspects of withdrawal. We therefore investigated the molecular
      mechanisms by which dopamine psychostimulant drugs induce prodynorphin gene
      expression in vivo and in rat primary striatal cultures. We demonstrate that
      three recently described cAMP response elements (CREs), rather than a previously
      reported noncanonical AP-1 site, are critical for dopamine induction of the
      prodynorphin gene in striatal neurons. CRE-binding protein (CREB) binds to these
      CREs in striatal cell extracts and is phosphorylated on Ser-133 after dopamine
      stimulation in a D1 dopamine receptor-dependent manner. Surprisingly, following
      chronic administration of amphetamine, levels of phosphorylated CREB are
      increased above basal in rat striatum in vivo, whereas c-fos mRNA is suppressed
      below basal levels. D1 receptor-mediated CREB phosphorylation appears to mediate
      adaptations to psychostimulant drugs in the striatum.

PMID- 7718245
TI  - Structural determinants of allosteric regulation in alternatively spliced AMPA
      receptors.
AB  - The flip and flop splice variants of AMPA receptors show strikingly different
      sensitivity to allosteric regulation by cyclothiazide; heteromers assembled from
      GluR-A and GluR-B also exhibit splice variant-dependent differences in efficacy
      for activation by glutamate and kainate. The sensitivity for attenuation of
      desensitization by cyclothiazide for homomeric GluR-A was solely dependent upon
      exchange of Ser-750 (flip) and Asn-750 (flop), and was unaffected by mutagenesis
      of other divergent residues. In contrast, substantial alteration of the relative
      efficacy of glutamate versus kainate required mutation of multiple residues in
      the flip/flop region. Modulation by cyclothiazide was abolished by mutation of
      Ser-750 to Gin, the residue found at the homologous site in kainate-preferring
      subunits, whereas introduction of Ser at this site in GluR6 imparted sensitivity
      to cyclothiazide.

PMID- 7718246
TI  - Serotonin modulates the voltage dependence of delayed rectifier and Shaker
      potassium channels in Drosophila photoreceptors.
AB  - We describe the in situ modulation of potassium channels in a semi-intact
      preparation of the Drosophila retina. In whole-cell recordings of photoreceptors,
      rapidly inactivating Shaker channels are characterized by a conspicuously
      negative voltage operating range; together with a delayed rectifier, these
      channels are specifically modulated by the putative efferent neurotransmitter
      serotonin. Contrary to most potassium channel modulations, serotonin induced a
      reversible positive shift in the voltage operating range, of +30 mV for the
      Shaker channels and +10-14 mV for the delayed rectifier. The maximal current
      amplitudes were unaffected. Modulation was not affected by the subunit-specific
      Shaker mutations ShE62 and T(1;Y)W32 or a null mutation of the putative
      modulatory subunit eag. The modulation of both channels was mimicked by
      intracellularly applied GTP gamma S.

PMID- 7718247
TI  - A single site on the epsilon subunit is responsible for the change in ACh
      receptor channel conductance during skeletal muscle development.
AB  - Four critically positioned amino acids on each of the alpha, beta, delta, and
      gamma subunits of the Torpedo nicotinic acetylcholine receptor are determinants
      of channel conductance. Our results show that the gamma and epsilon subunits of
      Xenopus muscle receptors are identical at all four positions, despite the fact
      that alpha 2 beta delta epsilon receptors have a 50% greater conductance than
      alpha 2 beta delta gamma receptors. Instead, the functional difference is
      conferred by a single charged residue that lies extracellular to all four
      positions, corresponding to a location in the Torpedo receptor previously shown
      to have no influence on conductance. Substitution of a positively charged lysine
      residue in gamma by the neutral methionine in epsilon at this extra-cellular
      position is responsible for the increased conductance during maturation of the
      amphibian neuromuscular junction.

PMID- 7718248
TI  - A mutated acetylcholine receptor subunit causes neuronal degeneration in C.
      elegans.
AB  - Neurotoxicity through abnormal activation of membrane channels is a potential
      cause of neurodegenerative disease. Here we show that a gain-of-function
      mutation, deg.3(u662), leads to the degeneration of a small set of neurons in the
      nematode C. elegans. The deg.3 gene encodes a nicotinic acetylcholine receptor
      alpha subunit, which in the region of transmembrane domain II is most similar to
      the neuronal alpha 7 subunits from rat and chicken. The u662 mutation changes a
      residue in the second transmembrane domain, the domain thought to form the
      channel pore. A similar change in the equivalent amino acid in the chick protein
      produces channels that desensitize slowly. Channel hyperactivity may underlie the
      degenerations seen in the C. elegans deg.3(u662) mutants, since antagonists of
      nicotinic acetylcholine receptors suppress the deg-3(u662) mutant phenotypes.

PMID- 7718249
TI  - beta-amyloid fibrils induce tau phosphorylation and loss of microtubule binding.
AB  - A central issue in the pathogenesis of Alzheimer's disease (AD) is the
      relationship between amyloid deposition and neurofibrillary tangle formation. To
      determine whether amyloid fibril formation affects the phosphorylation state of
      tau, primary cultures of fetal rat hippocampal and human cortical neurons were
      treated with beta-amyloid (beta A) in a soluble, amorphous-aggregated, or
      fibrillar form. Fibrillar beta A, but not soluble or amorphous-aggregated beta A,
      markedly induces the phosphorylation of tau at Ser-202 and Ser-396/Ser-404,
      resulting in a shift in the tau M(r) in human cortical neurons.
      Hyperphosphorylated tau accumulates in the somatodendritic compartment of
      fibrillar beta A-treated neurons in a soluble form that is not associated with
      microtubules and is incapable of binding to microtubules in vitro.
      Dephosphorylation of beta A-induced tau restores its capacity to bind to
      microtubules. Thus, amyloid fibril formation alters the phosphorylation state of
      tau, resulting in the loss of microtubule binding capacity and somatodendritic
      accumulation, properties also exhibited by tau in the AD brain. Amyloid fibril
      formation may therefore be a cause of abnormal tau phosphorylation in AD.

PMID- 7718250
TI  - Determination of cause of death among breast cancer cases in the Swedish
      randomized mammography screening trials. A comparison between official statistics
      and validation by an endpoint committee.
AB  - Between 1976 and 1982, four randomized mammography screening trials started in
      five screening centres in Sweden, involving 282,777 women (156,911 invited and
      125,866 controls) with the aim to study if invitation to screening reduced the
      breast cancer mortality. An overview of the trials was performed to reduce the
      confidence intervals for the relative risk estimates. All 1,296 deaths occurring
      in women with breast cancer detected after randomization were evaluated by an
      independent endpoint committee (EPC), consisting of four physicians who reviewed
      collected medical information that was blinded regarding mammography screening.
      If there was disagreement between the EPC members at the initial individual
      evaluation the final classification was made at consensus meetings. In only 6.9%
      (n = 89) of the cases was there disagreement as to whether breast cancer was or
      was not the underlying cause of death. It was also found that 'breast cancer as
      underlying cause of death' and 'breast cancer as underlying or contributory cause
      of death' according to Statistics Sweden resulted in relative risk estimates very
      similar to those based on the classification by the EPC. The study thus supports
      the use of official health statistics in the evaluation of randomized breast
      screening trials in Sweden.

PMID- 7718251
TI  - Validity of breast cancer registration from one hospital into the Swedish
      National Cancer Registry 1971-1991.
AB  - To validate the Swedish Cancer Registry concerning breast tumours in female
      residents of Malmo 1971-1991, registry-entries were compared with clinical
      records. Correctness and completeness of entries was determined for invasive
      breast cancer (BC) and cancer in situ of the breast (CIS). As BC were registered
      3,646 tumours. Of these 3,403 (93.3%) were confirmed as BC. Completeness was good
      with 1.1% of diagnosed tumours missing. Correctness of registered cases of CIS
      was 93.3%, but completeness only 63.3%. Most missing cases were registered as BC.
      In bilateral cancer correctness was 78.0% and completeness 77.2%. All aspects of
      registration improved during the period. Most differences between diagnosed and
      registered cases were due to coding CIS of intraductal type as BC. This practice
      changed in 1980 resulting in improved precision. Using registry data for
      epidemiological research the question of their validity must be addressed.
      Special consideration should be paid to coding practice at the registry.

PMID- 7718252
TI  - In vivo efficacy of novel synthetic enediynes 1.
AB  - We have investigated the biodistribution, toxicity, and antitumor activity of a
      new type of synthetic compound containing an enediyne functional group capable of
      benzenoid diradical generation. The design of this cytotoxic molecule was based
      on the structures of naturally occurring enediyne antibiotics. Compared to the
      natural compounds, the synthetic enediyne displayed cytotoxicities approaching
      the natural analogs. Using a tritiated analog, biodistribution studies revealed
      relatively high uptake levels in kidney, lung, heart, and spleen with moderate
      levels in all other organs. Antitumor activity was apparent, with significant
      tumor regression observed in athymic nude mice with established M21 melanomas.
      Significant tumor antiproliferative effects were observed against L-1210 mouse
      leukemia, A549 lung carcinomas and PC3 prostate carcinomas in athymic nude mice,
      and against EMT-6 mouse mammary adenocarcinomas in Balb/cByJ mice. These results
      suggest that synthetic enediynes may be useful therapeutic compounds since their
      design reduces systemic toxicity compared to the natural products, without
      compromising antitumor activity. The relatively low sensitivity of many
      established cell lines to synthetic enediynes suggests a discrepancy between cell
      culture and in vivo tumor cytotoxicities. Adaptation of some cell lines for in
      vivo proliferation may affect their sensitivity to synthetic enediynes.

PMID- 7718253
TI  - Risk of second cancers among lung cancer patients.
AB  - The risk of a second cancer among lung cancer patients was investigated using
      Finnish Cancer Registry data from 1953 to 1989. Among the 36,528 patients with a
      primary cancer of the lung, 504 new cancers were diagnosed six months or more
      after the diagnosis of lung cancer, yielding a standardized incidence ratio
      significantly lower than expected (SIR = 0.81). A significant excess of cancers
      of the larynx (SIR = 2.10) and urinary bladder (SIR = 1.35) was observed Among
      lung cancer patients below 60 years of age, the risks of oesophageal cancer (SIR
      = 2.47) and kidney cancer (SIR = 2.48) were also significantly elevated. The risk
      of a second cancer among lung cancer patients increased with the length of follow
      up, and there was some indication of an excess risk of oesophageal cancer and
      leukaemia among lung cancer patients subject to radiotherapy.

PMID- 7718254
TI  - The relationship between proliferating cell nuclear antigen (PCNA), nuclear DNA
      content and mutant p53 during genesis of cervical carcinoma.
AB  - Proliferating cell nuclear antigen (PCNA), nuclear DNA content and mutant p53
      overexpression were studied by means of image cytometry and immunohistochemistry
      respectively in normal mucosa (n = 10), in mild (n = 16), moderate (n = 9) and
      severe (n = 17) atypical lesions, as well as in squamous cell carcinomas (n = 36)
      of the cervix uteri. The results show that increasing histopathological atypia in
      the cervical mucosa was correlated to an initial increase of PCNA followed by
      distinct aneuploidy and p53 overexpression. The data are suggested to contribute
      to a better understanding of the genesis of cervical carcinoma, and to indicate
      that the coexistence of both distinct aneuploidy and p53 immunoreactivity can be
      used to decide if a cell population is neoplastic, whereas the absence of p53
      overexpression does not necessarily exclude neoplasia. This diagnostic procedure
      can be suggested to improve early detection of intraepithelial squamous
      neoplasia.

PMID- 7718255
TI  - Serum cytokines in gestational trophoblastic diseases.
AB  - Interleukin 1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha) were assayed by 125I immunoradiometric assay in sera of 42
      cases of vesicular mole (VM), 24 cases of choriocarcinoma and 23 normal pregnant
      women at their first trimester (controls). According to pathologic diagnosis and
      serial serum hCG beta assays, the cases with VM and choriocarcinoma were
      subdivided into remission and progressive tumor groups. The progressive tumor
      groups--both VM and choriocarcinoma--showed marked elevations of serum IL-1 beta,
      IL-6 and TNF alpha. For choriocarcinoma in remission this elevation was
      considerably less pronounced. The VM cases in remission had only a slight
      increase of the mean serum IL-6 value and none of the cases had elevated IL-1
      beta or TNF values. These results may indicate that serum IL-1 beta and TNF-alpha
      assays are valuable biomarkers in the differential diagnosis of gestational
      trophoblastic disease (GTD). Moreover, normal values of these cytokines may rule
      out high-risk GTD, whereas markedly elevated values may indicate poor prognosis.

PMID- 7718256
TI  - Regeneration of parotid acinar cells after high radiation doses. A morphological
      study in rat.
AB  - The acute and late effects of fractionated irradiation on rat parotid gland
      acinar cells were studied by light and electron microscopy. At 10 days after the
      last irradiation session (6 Gy or 9 Gy daily during five consecutive days) no
      effects were seen. At 180 days, minor loss of acini was detectable after a total
      dose of 30 Gy. After 45 Gy a massive acinar loss was seen at that time; the
      number of acini had diminished and minor duct-like structures and scattered
      amounts of fibrous stroma dominated the slides. The remaining acini were
      disorganized and usually larger compared with the control side and to non
      irradiated animals. The acinar cells appeared larger than in the controls. The
      ducts were better preserved but the intercalated ducts often seemed to be larger
      than normal. We suggest that this phenomenon indicates a remaining capacity of
      the parotid gland to regenerate acinar cells even after high radiation doses.

PMID- 7718257
TI  - Histological changes after fractionated whole or partial irradiation of the
      rabbit urinary bladder.
AB  - Effects of x-irradiation on the urinary bladder of male New Zealand rabbits were
      studied by means of light microscopy 100 weeks after exposure. The absorbed dose
      was 33, 36 or 39 Gy given in 5 daily fractions administered to the whole, the
      cranial or the caudal part of the bladder. The changes in the epithelium and in
      the muscular tissue were dose-dependent while the changes in the submucosa and in
      the extramuscular layer were not. The transitional epithelium was generally
      either atrophic or hyperplastic. If dysplastic or neoplastic changes were seen,
      the involved areas were mostly surrounded by an apparently normally
      differentiated epithelium and the highly specialized superficial cells lining the
      bladder cavity were always present. The submucosal and muscular tissues showed
      fibrosis and changes in blood vessels and, sometimes also in lymph vessels.

PMID- 7718258
TI  - Radiation effects on S-phase duration, labelling index, potential doubling time
      and DNA distribution in head and neck cancer xenografts.
AB  - The effect of irradiation on S-phase duration (Ts), labelling index (LI),
      potential doubling time (Tpot), and cell cycle phase distributions was determined
      by DNA flow cytometry in xenografted human squamous cell carcinoma of the head
      and neck (SCCHN). Tumours were treated with a single dose of 3 Gy, and excised at
      intervals over a 90-h period. Six hours before each excision the tumours were
      labelled in vivo with bromodeoxyuridine (BrdUrd). Although the growth rate of
      irradiated tumours was comparable with that of untreated controls, analysis of
      BrdUrd uptake revealed a transient reduction of LI and a prolongation of Ts in
      irradiated tumours. Maximum mean Tpot was 931 days in irradiated tumours as
      compared to 13 days in untreated controls. The variations in Ts, LI and Tpot all
      occurred within the first hours after irradiation; during the remainder of the
      observation time, the values of the variables did not differ from those of
      untreated controls. In irradiated tumours the distribution of cells according to
      DNA content changed significantly on three occasions during the observation
      period: 1) Parallel to the initial lowering of LI and prolongation of Ts there
      was a transient increase in the proportion of cells in G0/G1 and a decrease in
      the proportion of cells in S and G2; 2) At 18 h, the most pronounced cell cycle
      phase redistribution occurred when the G0/G1 fraction decreased and the S and G2
      phase fractions increased; 3) At 66 h (i.e., approximately one cell cycle later),
      the pattern was the same as that after 18 h. The findings suggest that the
      transient prolongation of DNA replication seen in SCCHN cells immediately after a
      single radiation dose is a symptom of DNA damage inflicted during late G1 or
      early S-phase, and that this disturbance in DNA synthesis is associated with the
      subsequent accumulation of cells in G2 phase.

PMID- 7718259
TI  - Azidothymidine (AZT) as a potential modifier of radiation response in vitro.
AB  - The potential effect of AZT as a thymidine analogue on radiation response in
      vitro was investigated. Two human cell lines (WiDr and HeLa) were used. The
      effect of 10 microM AZT on exponentially growing cells was studied after
      different exposure times (24, 48 and 72 h). The surviving fraction (clonogenic
      assay) or metabolic activity (MTT assay) after irradiation of AZT-exposed cells,
      was compared to unexposed irradiated controls. Flow cytometry was used to assess
      the cell-cycle effect of pre-exposure of exponentially growing cells to AZT. AZT
      had a radioprotective effect for all experimental time points as far as WiDr was
      concerned. For HeLa the effect was significant at 24 h. Cell-cycle analysis
      showed a significant accumulation in S-phase at 72 h for WiDr. For HeLa there was
      a significant accumulation in S-phase at 48 h. We conclude that under the
      reported experimental conditions, AZT as a thymidine analogue seems to reduce the
      cytotoxic effect of irradiation.

PMID- 7718260
TI  - Effects of sucralfate on mucositis during and following radiotherapy of
      malignancies in the head and neck region. A double-blind placebo-controlled
      study.
AB  - Radiotherapy of head and neck malignancies is accompanied by oral discomforts,
      such as epithelitis, pain and functional impairment. This can lead to chronic
      sequalae with subjective distress such as loss of taste and xerostomia and
      pronounced decrease in quality of life. Thus, the need to reduce the mucosal
      damage following radiotherapy is obvious. Therefore, we investigated the possible
      ability of sucralfate, an aluminium hydroxide complex of sulphated sucrose used
      in the treatment of gastric ulcer, in preventing oral discomfort in patients
      treated with curative intent for malignancies in the head and neck region. The
      study was double-blind, placebo-controlled and randomized and included 50
      consecutive patients. The study demonstrated that the proportion of patients with
      severe mucosal reactions was significantly lower in the sucralfate group than in
      the placebo group.

PMID- 7718261
TI  - Influence of boost technique (external beam radiotherapy or brachytherapy) on the
      outcome of patients with carcinoma of the base of the tongue.
AB  - We reviewed 90 patients with squamous cell carcinoma of the base of the tongue.
      Fifty-three patients were treated with external beam radiotherapy alone (3 T1, 11
      T2, 21 T3, and 18 T4 tumors) and thirty-seven patients were treated with external
      beam radiotherapy plus brachytherapy boost (4 T1, 15 T2, 11 T3, and 7 T4 tumors).
      For patients with T1, T2 and T3 primaries, the actuarial 3-year local relapse
      free survival was 42% following external beam radiotherapy alone and 67%
      following external beam radiotherapy plus brachytherapy (p < 0.05). The actuarial
      3-year cause specific survival for these T-stages was 37% for patients treated
      with external beam radiotherapy alone and 53% for patients treated with external
      beam radiotherapy plus brachytherapy (p = 0.1). In the Cox multivariate analyses
      restricted patients with T1, T2 and T3 staged tumors, treatment modality was the
      only predictor for local control but no influence on specific survival was found.
      The trend towards significant differences in specific survival found in the
      univariate comparison of both treatment modalities was probably due to the
      significantly higher number of N-positive patients treated with external beam
      radiotherapy alone. When all stages were included in the Cox analysis, low
      hemoglobin level, invasion of deep muscle, number of palpable nodes, and history
      of weight loss significantly influenced the outcome. Soft tissue necrosis
      occurred more frequently in patients treated with external beam radiotherapy plus
      brachytherapy (33% vs. 10%, p = 0.52).

PMID- 7718262
TI  - Comparative study on reversal efficacy of SDZ PSC 833, cyclosporin A and
      verapamil on multidrug resistance in vitro and in vivo.
AB  - A non-immunosuppressive cyclosporin, SDZ PSC 833 (PSC833), shows a reversal
      effect on multidrug resistance (MDR) by functional modulation of MDR1 gene
      product, P-glycoprotein. The objective of the present study was to compare the
      reversal efficacy of three multidrug resistance modulators, PSC833, cyclosporin A
      (CsA) and verapamil (Vp). PSC833 has approximately 3-10-fold greater potency than
      CsA and Vp with respect to the restoring effect on reduced accumulation of
      doxorubicin (ADM) and vincristine (VCR) in ADM-resistant K562 myelogenous
      leukemia cells (K562/ADM) in vitro and also on the sensitivity of K562/ADM to ADM
      and VCR in in vitro growth inhibition. The in vivo efficacy of a combination of
      modifiers (PSC833 and CsA: 50 mg/kg, Vp 100 mg/kg administered p.o. 4 h before
      the administration of anticancer drugs) with anticancer drugs (ADM 2.5 mg/kg
      i.p., Q4D days 1, 5 and 9, VCR 0.05 mg/kg i.p., QD days 1-5) was tested in ADM
      resistant P388-bearing mice. PSC833 significantly enhanced the increase in life
      span by more than 80%, whereas CsA and Vp enhanced by less than 50%. This
      reversal potency, which exceeded that of CsA and Vp, was confirmed by therapeutic
      experiments using colon adenocarcinoma 26-bearing mice. These results
      demonstrated that PSC833 has significant potency to reverse MDR in vitro and in
      vivo, suggesting that PSC833 is a good candidate for reversing multidrug
      resistance in clinical situations.

PMID- 7718263
TI  - Ondansetron versus metoclopramide as antiemetic treatment during cisplatin-based
      chemotherapy. A prospective study with special regard to regard to electrolyte
      imbalance.
AB  - Cancer patients selected for cisplatin-based chemotherapy were randomly divided
      into two groups (42 patients in each) which received either metoclopramide or
      ondansetron as antiemetics. Metoclopramide was given i.v. with 5 doses of 2 mg/kg
      starting 30 min before the cisplatin infusion and continued with one dose every 3
      h. Ondansetron was given with a first injection of 8 mg i.v. 30 min before the
      cisplatin infusion; the patients were given 8 mg orally 5 and 10 h after the
      cisplatin infusion followed by 8 mg x 3 during the next two days. In the present
      study ondansetron was superior to metoclopramide concerning antiemetic efficacy
      and gave also less side-effects as diarrhea, dizziness, extrapyramidal symptoms
      and electrolyte imbalance (sodium, potassium, magnesium, phosphorous) during the
      first 24 h following the cisplatin infusion.

PMID- 7718264
TI  - Mechanisms of cyclophosphamide resistance in a human myeloid leukemia cell line.
AB  - The 4-hydroperoxycyclophosphamide (4HC)-resistant B5-180(3) subline of the cloned
      KBM-7/B5 cell line was developed as a model of induced cyclophosphamide
      resistance in human myeloid leukemia. Based on IC90 values, this subline was
      approximately 20-fold resistant to 4HC. Furthermore, it was significantly cross
      resistant to phosphorodiamidic mustard (PM), whose cytotoxicity is independent of
      aldehyde dehydrogenase (ADH). Using alkaline elution we found that the resistant
      line had decreased initial levels of DNA interstrand cross-links (ISCs) following
      4HC but not PM treatment. The resistant cells also appeared to remove ISCs from
      their DNA more rapidly than the parental cells. Our data therefore suggest that
      4HC resistance in the B5-180(3) subline is multifactorial; ADH is an important
      mediator of its resistance to ISC induction by 4HC, while a second process, which
      may involve an increased ability to tolerate drug-induced DNA damage, appears to
      be important for its resistance to both 4HC and PM. The B5-180(3) cells were also
      cross-resistant to gamma-radiation (approximately 1.7-fold at a surviving
      fraction of 0.1); if generally applicable, such effects could have important
      clinical implications, since pretransplant total body irradiation is a major
      component of the eradication of leukemic cells.

PMID- 7718265
TI  - Influence of 5-fluorouracil on serum lipids.
AB  - The effect of the cytotoxic drug 5-fluorouracil (5-FU) on plasma lipid levels was
      studied in patients and animals. Seven patients with metastatic carcinoma of the
      colon and three with advanced breast cancer were treated with 5-FU monotherapy by
      i.v. push at a dose of 500 mg/m2/d for 3-5 consecutive days. The animal group
      comprised 9 rabbits treated with 5-FU by i.v. push at 12-18 mg/kg/d for 2
      consecutive days. Measurements of serum lipid levels were performed before and 2
      and 4 weeks after 5-FU administration. No obvious change of diet, body weight and
      bowel habits occurred during the study period. A significant reduction of total
      plasma cholesterol was observed in both patients and animals. The triglyceride
      levels were also reduced in the rabbits. Maximal cholesterol-lowering effect was
      observed in patients and rabbits with higher baseline cholesterol levels. The
      results suggest that 5-FU might interfere with lipid metabolism.

PMID- 7718266
TI  - Cisplatin and ifosfamide in patients with advanced squamous cell carcinoma of the
      uterine cervix. A phase II trial.
AB  - Thirty patients with advanced squamous cell carcinoma of the cervix were included
      in a phase II study with cisplatin (DDP) and ifosfamide (IF)/mesna. They received
      a median of 4 courses of chemotherapy and were all evaluable for response and
      toxicity. Each cycle consisted of 2,500 mg/m2 IF i.v. days 1-5; mesna 500 mg/m2
      i.v. at hours 0 and 2, and 1,000 mg/m2 per os at hours 6 and 10, days 1-5; DDP 20
      mg/m2 i.v., days 1-5. Cycles were repeated every 4 weeks. One patient obtained CR
      and 14 PR giving an overall response rate of 50%. Mean duration of response was
      21 months. Anemia grade 3 developed in 7 patients, leukopenia grade 3 in 9
      patients and grade 4 in one patient; thrombopenia grade 3 in 2; creatinine
      clearance grade 3 in one; CNS grade 3 in one and cystitis grade 3 in one patient.
      Overall median survival time was about 25+ months (3-63+); after a follow-up of
      70 months, 11 patients (37%) are still alive with a median survival of 31+
      months. IF plus DDP seems to be a good combination for treatment of advanced
      cervical cancer, with acceptable tolerance and response rate.

PMID- 7718267
TI  - Moyamoya vasculopathy after cranial irradiation--a case report.

PMID- 7718268
TI  - Kaposi's sarcoma in the course of juvenile myelodysplastic syndrome.

PMID- 7718269
TI  - Cisplatin-induced hyponatremia and renal sodium wasting.

PMID- 7718270
TI  - Is CA 125 actually a tumor marker for ovarian cancer?

PMID- 7718271
TI  - Performance of new Scanditronix semiconductor detectors for in vivo dosimetry.

PMID- 7718272
TI  - Mitomycin C (MMC) and unconventional fractionation (V-CHART) in advanced head and
      neck cancer.

PMID- 7718273
TI  - [Study on the specific binding site of NF-k B-like factor at the 5' upstream
      region of human lymphotoxin gene].
AB  - Lymphotoxin(LT) is a glycoprotein secreted by activated T lymphocytes. The
      expression of LT gene is primarily controlled at the level of transcription. By
      using human LT DNA as a probe, we have carried out a RNA dot blotting test and
      found that the longer the Jurkat cells exposed to the PMA and PHA, the more was
      the endogenous LT mRNA. Results of gel retardation assay showed that nuclear
      extract from Jurkat cells treated with PMA and PHA formed different complexes.
      Changes in the complex patterns were observed in different time of PMA and PHA
      induction. A specific protein-binding site was mapped to a 22bp sequence at the
      5' upstream region of human LT gene by DNase I footprinting analysis. This region
      is similar to the sequence recognized by the proteins of NF-KB family. The
      results of fragment competition test and homology analysis indicated that the 22
      bp sequence contains a KB-like motif only, which located at base pairs -100 to 
      90(5' -GGGGGCTTCCC-3'). Thus the NF-KB-like factors were involved in the protein
      DNA interaction. Furthermore, there were more than one retarded bands appearing
      in the gel retardation assay. It suggested that there may be various kinds of NF
      KB-like factors involved in the regulation of LT gene transcription at the same
      site.

PMID- 7718274
TI  - [A genetic study of adult polycystic kidney disease].
AB  - The 3'HVR has been considered as the most useful probe in making the linkage
      analysis of adult polycystic kidney disease (APKD). We examined three APKD
      families using this probe. Their polymorphism information was then computed for
      linkage study using LINKAGE package and computer programme HOMOG for homogeneity
      test. One family was defined as non PKD 1, because the disease locus was failed
      to show linkage to the 3'HVR marker. Of the other two families, one can still not
      be identified as non PKD1, but had distinguishable meiotic recombinations,
      another was in favour of linkage to 3'HVR and therefore judged to be PKD1. The
      presence of genetic heterogeneity could significantly reduce the value of linked
      probe analysis as a tool for gene diagnosis of APKD.

PMID- 7718275
TI  - [Study of super-structure of eukaryotic chromosomes. I. The super-structure of
      metaphase chromosomes in pigs].
AB  - The super-structure of fine and close metaphase chromosomes was studied with the
      optical micro multistage amplifying system designed by author himself, which
      could show the fine structure about 15nm in diameter of chromosomes. The
      micrographs of chromosomal super-structure made of DNA-nuclear protein or non
      histone protein were shown respectively in the present paper. The chromotids were
      composed of long fibres about 20-30nm in diameter in a regular helical form
      directly. The characters and parameters of chromosomal super-structure were
      described, and a dynamical helical model of the chromosomal structure was
      suggested.

PMID- 7718276
TI  - [Study on evolutionary genetics of Drosophila auraria species complex--cladistic
      analysis and phenetic analysis].
AB  - In the present paper, seventeen geographic strains of D. auraria species complex
      and five geographic strains of other four species, which belong to the montium
      species subgroup were biochemically examined for the construction of phylogenetic
      tree based on phenetic and cladistic analysis. Eighteen isoenzymes were analyzed
      by isoelectric focusing polyacrylamide gel electrophoresis in the above twenty
      two geographic strains. The phenogram of the D. auraria species complex is
      supported by UPGMA program of phenetic analysis. It was found that: 1. D.
      auraria, D. triauraria and D. quadraria grouped as an type are more closely
      related to one another, and D. biauraria, D. subauraria are more closely related
      to each other, while the former three species are distantly related to the latter
      two species. 2. The genetic identity between two geographic strains of same
      species is higher than the genetic identity between different species, except the
      geographic strain T-KM of D. triauraria. 3. The geographic strain T-KM, one of
      the D. triauraria from the southeast isolated islands Kametoku [symbol: see text]
      of Japan is far more distantly related to the other geographic strains of it. We
      suggest that the new species or subspecies are diverged from D. triauraria will
      be due to the geographic speciation mechanisms. 4. The genetic differentiation
      among eight geographic strains of D. triauraria are much larger than those among
      three geographic strains of D. auraria, which may be related to their different
      inhabitation environment as well as their flying ability. On the other hand, a
      cladistic analysis of the D. auraria species complex are made in the present
      paper.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718277
TI  - [The upstream sequence of cholera toxin B subunit gene: effect on CTB
      expression].
AB  - In this work, we have studied the effect of cholera toxin A structure gene on the
      expression of the distal ctxB gene by the methods of deletion and frame-shift
      mutation. The results showed that: The expression level of Plasmid pUC19CTB,
      which was constructed by cloning the XbaI-EcoRI restriction fragment into pUC19
      and ctxA gene was out-frame with lacZ' gene, is about 30 micrograms/ml; If a
      frame shift mutation was introduced at XbaI site of pUC19CTB so that the cholera
      toxin A gene was inframe with lacZ' and could be translated, the expression level
      of ctxB was decreased to 12 micrograms/ml; When A further deletion from XbaI to
      ClaI of cholera toxin A gene (about 550bp) was made and ctxA was outframe with
      LacZ', ctxB expression was decreased two fold compared to pUC19CTB; If the ctxA
      was inframe with LacZ' so ctxA gene could be translated, the expression level of
      CTB is much lower than the plasmid outframe with lacZ'. These observations could
      not be explained by the current knowledge about genetical regulation of cholera
      toxin operon. The promoter we found located in the cholera toxin A subunit gene,
      which is responsible for the expression of cholera toxin B subunit, may answer
      the question why the 550bp non-coding sequence could enhance the expression of
      cholera toxin B subunit.

PMID- 7718278
TI  - [Role of EcoRI-BclI fragment at the promoter upstream region on the expression of
      alpha-amylase gene].
AB  - A series of plasmids derived from pNL201 with the promoter upstream region of
      alpha-amylase gene of B. licheniformis have been constructed. In the meantime, a
      series of plasmids derived from pAmy41 with full alpha-amylase gene have also
      been constructed and they have different promoter upstream region with the EcoRI
      BclI fragment deleted or partial destroyed. The alpha-amylase activity of the
      engineering strains carrying alone or double plasmids has been determined. The
      statistical results show that the EcoRI-BclI fragment possesses negative
      regulation in the expression of alpha-amylase gene in B. subtilis.

PMID- 7718279
TI  - CT and MRI of diffuse liver disease.
AB  - CT and MRI contribute important information to the clinical evaluation of diffuse
      liver disease. In some cases, these modalities can establish a diagnosis that was
      not ascertained histologically, which is often the case when sampling errors
      prevent a definitive tissue diagnosis. Characteristic alterations of liver
      attenuation on CT, signal changes on MRI, and morphological changes appreciated
      with both modalities can be used to diagnose fatty infiltration, some parenchymal
      deposition diseases, and cirrhosis. Furthermore, hepatocellular disease can be
      confirmed in the setting of indeterminate clinical and laboratory findings.
      Significant overlap in the imaging findings of this wide range of disorders
      continues to limit specificity; however, at a minimum, these techniques provide a
      rapid means to a noninvasive evaluation that often guides clinical decisions.
      Faster scanning techniques available with CT and MRI may provide additional
      information by assessing contrast dynamics. This review of CT and MRI in diffuse
      liver disease considers the diagnostic utility and clinical implications of these
      modalities. Pathological findings relevant to imaging considerations are
      discussed.

PMID- 7718280
TI  - Clinical perspective: the importance of imaging in diffuse liver disease and
      hepatic vascular disorders.
AB  - The diagnosis of hepatobiliary disorders is based on the patient's history and
      physical examination and is augmented by laboratory findings, imaging studies,
      and histology. Radiographic imaging is especially helpful for identifying
      structural lesions and vascular abnormalities. In cholestatic disease, imaging of
      the biliary tree is essential to identify extrahepatic biliary obstruction. In
      hepatocellular diseases, imaging studies narrow the differential diagnosis and
      guide further testing. In this clinical overview, the role of radiographic
      imaging in hepatobiliary disorders is reviewed.

PMID- 7718281
TI  - Sonographic diagnosis of hepatic vascular disorders.
AB  - Perhaps the most valuable application of duplex sonography in the abdomen is in
      the diagnosis of vascular disorders of the liver. Duplex sonography provides an
      accurate assessment of the portal and hepatic venous systems that is both
      noninvasive and convenient, because the examination can be conducted at the
      bedside. In this article, the normal features of portal and hepatic venous flow
      are considered as well as the sonographic manifestations of pathological
      conditions, including: (1) portal hypertension; (2) portosystemic collaterals;
      (3) portal vein thrombosis; and (4) hepatic vein thrombosis (Budd-Chiari
      syndrome).

PMID- 7718282
TI  - Hepatic vascular diseases: CT and MRI.
AB  - Continued development of CT and MRI techniques has allowed these modalities to
      detect most hepatic vascular diseases, often obviating more invasive tests. In
      this article, the techniques for hepatic vascular diagnosis are reviewed, with
      emphasis on spiral CT and two-dimensional MRI techniques, and then the major
      vascular diseases on which these two modalities have a significant diagnosing
      impact are considered.

PMID- 7718283
TI  - Sonography of transjugular intrahepatic portosystemic shunts.
AB  - Transjugular intrahepatic portosystemic shunting (TIPS) is an effective procedure
      for relieving portal hypertension. Sonography can usefully assist portal vein
      puncture. Color and duplex sonography after TIPS demonstrates changes in hepatic
      vascular hemodynamics, detects complications, and confirms shunt patency. A large
      proportion of shunts will develop progressive stenosis over 12 months. Stenosis
      occurs because of pseudointimal hyperplasia in the stent or in the hepatic vein.
      Patent shunts are characterized by velocities in excess of 70 cm/s and
      hepatofugal flow in the portal circulation distal to the shunt. Although the
      cause of the stenosis can rarely be seen, velocities of less than 50 cm/s
      indicate shunt stenosis. Loss of cardiac pulsatility is another useful sign of
      shunt stenosis. Regular sonographic monitoring reliably detects stenosis,
      allowing stent revision and preventing recurrence of bleeding.

PMID- 7718284
TI  - Sonographic diagnosis of diffuse liver disease.
AB  - Sonography provides valuable information about diffuse liver disease. This
      article reviews the normal features of hepatic parenchyma as well as the
      sonographic findings that characterize important pathological conditions.
      Included are hepatitis, opportunistic infection, diffuse metastasis, fatty liver,
      hepatic fibrosis, and cirrhosis.

PMID- 7718285
TI  - [Observation of cochlear microcirculation in experimental endolymphatic hydrops].
AB  - 30 guinea pigs were made as a model of endolymphatic hydrops by obliteration of
      endolymphatic sac and duct. Cochlear microcirculation of the lateral wall in the
      third turn was observed and recorded. The diameters and velocities of the vessels
      were analysed in IBAS image system. The stria vascular vessels and spiral
      ligament vessels were analysed respectively. The data showed: 1. 1, 2 and 3
      months after operation, the diameter of SLV averaely decreased 0.80 microns, 0.87
      microns, 1.21 microns (P < 0.05) respectively and velocity decreased 100.8
      microns/s, 141.0 microns/s, 136.0 microns/s (P < 0.05) respectively. 2. The
      diameter of SVV dilated 3 months after operation. With the elapse of time, SVV
      had a dilation tendency. These indicated that hydrops effect different changes in
      SLV and SVV. The overpressure of endolymphatic fluid may be the possible cause of
      changes in SVV and SLV.

PMID- 7718286
TI  - [The changes of Ca++ concentrations of endolymph and perilymph of the
      experimental endolymphatic hydrops].
AB  - The changes of Ca++ concentrations of endo- and perilymph were determined by
      using atomic absorption spectrophotometry in the guinea pig model which
      endolymphatic sac and duct were surgically obliterated one month ago. The results
      showed that the Ca++ concentrations of endolymph of hydropic ear was 0.181+0.129
      mmol/L (n = 9), and that of the control group was 0.020+0.014 mmol/L (n = 10).
      The paired t test (P < 0.01) showed significant difference. In perilymph, the
      concentrations of Ca++ of hydropic ear was 0.679+0.340 mmol/L (n = 10), and that
      of the control ears was 0.730+0.385 mmol/L (n = 10). The paired t-test (P > 0.05)
      showed no significant difference. The principle of the increase of Ca++
      concentrations in the endolymphatic hydrops was also discussed.

PMID- 7718287
TI  - [Investigation on vertigoes in childhood].
AB  - This paper analysed the pathogenesis and the vestibular test results of 87 cases
      of vertigo in the childhood below the age of 13 years old. 83 cases (95.4%) were
      vestibular peripheral lesions, and 4 cases were vestibular central lesions. 34.5%
      of them were benign paroxysmal vertigo and 14.9% were the Meniere's disease which
      all occurred at the age more than 9 years old. The appearances of ENG were
      semicircular canal hypofunction in 57 cases (65.5%). The function of ocular
      movement was abnormal in a few cases. The posturography results were compared
      with an age-matched control group. Posturographic recording showed length of
      locus and velocity increased in the thirteen patients of semicircular canal
      hypofunction.

PMID- 7718288
TI  - [Long-term result of endolymphatic sac drainage for Meniere's disease].
AB  - Ten cases of Meniere's disease were operated with endolymphatic mastoid shunt.
      All patients were followed up 3 to 5 years postoperatively. The results showed
      that all patients obtained satisfactory relief of Vertigo, and in most of the
      cases the symptom of the tinnitus was diminished or vanished, only one patient
      demonstrated hearing loss. The advantages of this surgery are: shorter
      hospitalization, fast recovery and a low potential for serious intracranial
      complications. The relation between the type of endolymphatic sac and the result
      of operation was discussed.

PMID- 7718289
TI  - [Posturography classification and clinical application].
AB  - W-I computerized posturography system, designed by authors of this article, was
      introduced. Using this system body sway was measured in 60 normal adults and 484
      patients with vertigo. 204 patients with confirmed clinical diagnoses were
      analyzed. Posturography (PSG) may be classified in 16 composite graphic types.
      Statistics suggested that PSG of 84.5% patients with unilateral peripheral
      vestibular dysfunction show that the left-right direction graphic type and of
      77.8% patients with front-back direction graphic type. The mechanism of the above
      mentioned types of posturography was discussed.

PMID- 7718290
TI  - [Low frequency rotational responses in bilateral caloric weakness patients].
AB  - Comparative analysis of low frequency (0.01-0.64Hz) sinusoidal harmonic
      acceleration (SHA) responses of 50 patients with bilateral caloric weakness
      (summed slowphase velocities SSVs < or = 20 degrees/s) revealed that SHA stimuli
      reflected not only the existence of bilateral caloric weakness but also the
      impairment degree. The phase values of the patients with SSVs < or = 10 degrees/s
      were greater than that of the patients with SSVs > 10 degrees/s and the normals,
      and the gain values of the patients with SSVs < or = 10 degrees/s were smaller
      than those with SSVs > 10 degrees/s and the normals. The patients with SSVs < or
      = 10 degrees/s showed more severe impairments than those with SSVs > 10
      degrees/s. However, even in the frequencies having higher impairment identifying
      rate, such as 0.01 and 0.02 Hz, about 30 percent of the patients with SSVs < or =
      10 degrees/s revealed rotational responses that were within normal limits. These
      findings indicated that even marked bilateral caloric reduction is in sufficient
      to diagnose vestibular loss.

PMID- 7718291
TI  - [Relationship between summating potentials and perilymphatic fistula].
AB  - Serial electrocochleogram (ECochG) recordings were obtained within 24 hours from
      40 guinea pigs with experimentally induced PLF, and the cochlears of 30 guinea
      pigs (60 ears) were histopathologically observed under light microscope. -SP
      occurred in 100% experimented ears within 1-3 hours after PLF, but distention of
      Ressner's membrane was found only in 30% ones. CAP thresholds and N1 latencies of
      10 animals were improved, accompanying disappearance of -SP in 6 of the 10
      animals in 24 hours after PLF. It is presumed that -SP is not a specifically
      electrophysiologic indicator of ELH, and that the generation of -SP may chiefly
      result from reversible damage of cochlear hair cells. The mechanical factor of
      basilar membrane displacement can hardly be considered as a main cause of SP
      abnormality. The mechanism of the ELH following PLF was also discussed.

PMID- 7718292
TI  - [Investigation on etiology of abnormal ratio of CD4/CD8 cells in allergic nasal
      mucosal epithelium].
AB  - The lymphocytes of nasal mucosal epithelium were separated and the phenotype
      number of CD3, CD4 and CD8 cells were identified with immunohistochemical
      staining under light microscope. The number was increased significantly in CD4
      cells and decreased in CD8 cells of rats' nasal epithelium after stimulation with
      histamine. Abnormal ratio of CD4 and CD3 cells in the allergic nasal epithelium
      tended to be normal after treatment with H2 antagonist. The results of our
      investigation demonstrated that histamine might cause the number of CD4 and CD8
      cells into disorder in allergic nasal mucosal epithelium and the H2 antagonist
      may be useful in the treatment of allergic rhinitis.

PMID- 7718293
TI  - [Nasal endoscopic middle meatal antrostomy].
AB  - Middle meatal antrostomy under nasal endoscope, a functional procedure which
      conforms to paranasal sinus physiology, has provided a new approach to
      reestablishing the ventilation and drainage of nasal cavity and paranasal sinus.
      A 3-15 month's follow-up of 75 patients with chronic sinusitis and polyps who had
      undergone endoscopic sinus surgery shows a higher patency rate of 86.7% and a
      lower closure rate of 13.3%. While for patients who received inferior meatal
      antrostomy the patency rate was 54.7% and the closure rate 45.3%. There was a
      significant difference (P < 0.01) between the two groups in patency rate and
      closure rate respectively. So the antrostomy of middle meatus appears to be
      better than that of inferior meatus. The clinical significance of middle meatal
      antrostomy on the basis of anatomy and physiology of paranasal sinus is
      emphasized in discussion.

PMID- 7718294
TI  - [Glutamyltranspeptidase (gamma-GT) activity in the serum and pharynx tissue of
      nasopharyngeal carcinoma patients].
AB  - The gamma-GT activity in the serum and pharynx tissue of both NPC patients (106)
      and pharyngitis patients (65) were detected with method of hydrolysis gamma
      glutamylnitrophenylamine. The 34 NPC patient's gamma-GT were assayed both before
      and after radiotherapy. The results indicated that the gamma-GT activities
      between the NPC patients and pharyngitis patients, and the activities before and
      after radiotherapy have significant differences. The investigation suggests that
      the determination of serum and pharynx tissue gamma-GT levels of NPC patients
      would help to diagnose and evaluate the curative effect for NPC.

PMID- 7718295
TI  - [Investigation of skull base in nasopharyngeal carcinoma].
AB  - 100 patients with destruction of skull base in nasopharyngeal carcinoma,
      confirmed by pathology and CT scanning before radiotherapy, were analysed. It
      showed that the primary characteristics of skull base destruction are headache
      and cranial nerve involvement. Although the destruction of skull base showed
      evident manifestation in TNM classification, it can be inferred that the erosion
      development probably took place within 1-6 months. Comparing the CT scanning with
      X-ray submento-vertical view, the result indicated that the erosions of the
      various positions of the skull base and the invasion of paranasal sinus,
      cavernous sinus and orbit were clearly displayed by CT scanning but only 23% was
      discovered by X-ray. There was significant difference between CT scanning and X
      ray, and CT scanning had more advantages. The relation between the erosion of the
      skull base and the invasion of parapharynx space and the metastatics of the
      cervical nodes were also discussed.

PMID- 7718296
TI  - [Determination of plasminogen activator of the head and neck tumor tissue].
AB  - Fibrin plate was used to determine plasminogen activator (PA) of the head and
      neck tumor tissue. The results revealed: 1. The specific activity of PA of
      primary malignant tumor and neck lymphatic metastatic nodes were higher than that
      of normal tissue near cancer and benign tumor tissue; 2. The specific activity of
      PA was enhanced as advance of tumors in clinical stage. This study implicated
      that PA released from cancer cells can catalyze and convert plasminogen to
      plasmin, which results in tissue degradation, invasion and metastasis of tumor.

PMID- 7718297
TI  - [Research of serum gamma-glutamyltranspeptidase in laryngeal cancer diagnosis and
      prognosis].
AB  - The results of serum gamma-GT activities of 36 laryngeal cancer patients, were
      compared with that of 40 patients of benign group and 61 normal persons of
      control group, the difference between the first group and the other two groups is
      statistically significant (P < 0.01), whereas the difference between the later
      two groups shows no significance (P > 0.05), so measuring the serum gamma-GT
      activity is a simple and useful method for laryngeal cancer diagnosis. By
      following up 9 laryngeal cancer patients, the results indicated that measuring
      serum gamma-GT activity at regular intervals after treatment is a simple and
      useful method for observing the therapeutic effect, and for monitoring tumor
      recurrence or metastases.

PMID- 7718298
TI  - [Voice rehabilitation with duck's bill silicone tube after laryngectomy].
AB  - The voice rehabilitation of 43 laryngectomized patients were performed with
      endoscopic tracheoesophageal fistulation for interposition of ducks bill silicone
      tube from 1986 to 1993. 12 cases were performed from 1986 to 1989. Voice
      rehabilitated in 7 cases (58.3%). 31 cases were performed from 1989 to 1993, of
      which 29 cases (93.3%) obtained voice successfully with criconphageal myotomy
      cricoid chondredomy and test of esophageal speech flowing during operation.

PMID- 7718299
TI  - [Study of vocal function following partial laryngectomy with computer analysis
      system].
AB  - Vocal function of 28 patients following partial laryngectomy was studied with HGF
      1 personal computer system. The system consists of spectrogram analysis of
      correlogram and sonogram. The result showed that different phonetic positions
      have different vocal functions. Vocal function of the patients who had new vocal
      cord and patients who received supraglottic hemilaryngectomy is nearly normal.
      Whereas vocal function of patients with supraglottic construction and speaking
      shunt is very poor. This system appears to be an objective and quantitative tool
      for vocal function study.

PMID- 7718301
TI  - Redtide in the Philippines.
AB  - 1. Redtide is a marine phenomenon that poses great risk to the health and
      economic livelihood of people in coastal areas. Paralytic shellfish poisoning
      develops when a person consumes molluscs containing toxic dinoflagellates and
      suffers neurological and/or gastrointestinal manifestations. 2. Four redtide
      incidents in the Philippines are presented. The manner in which the problems were
      managed are described. 3. The clinical features of redtide poisoning in the
      Philippines included gastro-intestinal and neurological features with deaths
      secondary to ventilatory failure. Mortality ranged from 0% to 12% in the
      different redtide episodes. 4. There are many lessons to be learned in handling
      this kind of natural disaster. For an effective toxicovigilance programme, there
      must be a central co-ordinating responsible organization, a clear definition of
      roles and functions and good inter-agency co-operation. Appropriate surveillance
      procedures, resources to intensify surveillance at times of risks, prompt warning
      system, and the ability to impose bans on consumption are also necessary. 5.
      Poisons centres can play an important role during times of redtide. This may
      include toxicovigilant activities, such as early warning and educational
      campaigns to consumers, and seminars in the recognition and management of
      paralytic shellfish poisoning. 6. The contribution of the epidemiologists in
      investigating and monitoring the extent of public health damage and patterns of
      poisoning in a coastal community is emphasized.

PMID- 7718300
TI  - Fluctuation of trace elements during methylmercury toxication and chelation
      therapy.
AB  - The aim of the present investigation was to check the fluctuation in essential
      elements, such as Na, K, Mg, Mn, Cu, Zn, Cr and Ni in the brain, spinal cord,
      liver and kidney of mice during methylmercury chloride (MMC) toxication and
      therapy with monothiols (N-acetyl-DL-homocysteine thiolactone and glutathione)
      and vitamins (vitamin B complex and E). Mercury deposition and its elimination
      during chelation therapy were also screened for comparative purposes. The animals
      were dosed for 7 days with MMC 1 mg/kg/d and some were then kept without
      treatment for a further. 7 days. Other MMC-treated animals were immediately given
      one of the above antidotes for 7 days. All the animals were sacrificed on the
      15th day. There was a decrease in all elements during MMC toxication with few
      exceptions, for example, copper was increased in the liver as was sodium in the
      kidney. Treatment with the thiols and vitamins restored the levels of these
      elements in certain tissues towards normal, but their concentrations remained
      abnormal in most instances. The fluctuations in the concentration of these
      elements were attributed to their association with various macromolecules.

PMID- 7718302
TI  - Lipid peroxidation and chemiluminescence during naproxen metabolism in rat liver
      microsomes.
AB  - 1. Rat liver microsomal suspension containing NADPH and MgCl2 was incubated at 37
      degrees C with naproxen, a non-steroidal anti-inflammatory drug. Thiobarbituric
      acid reactive substances (TBA-RS), high molecular weight protein aggregates and
      fluorescent substances were formed in the microsomal suspension. 2.
      Chemiluminescence was produced from the microsomal suspension. This
      chemiluminescence production was well correlated to the TBA-RS formation,
      indicating that the chemiluminescence production was closely associated with the
      lipid peroxidation. 3. The addition of SKF-525A to the microsomal suspension
      inhibited the production of TBA-RS, chemiluminescence and 6-demethylnaproxen (6
      DMN), the oxidative product of naproxen. Further, the antioxidant, alpha
      tocopherol and singlet oxygen quenchers like histidine, dimethylfuran and 1,4
      diazabicyclo[2,2,2]octane strikingly inhibited the productions of
      chemiluminescence and TBA-RS. 4. Neither naproxen nor 6-DMN caused lipid
      peroxidation in the absence of NADPH. Thus, lipid peroxidation and
      chemiluminescence during the oxidation of naproxen in liver microsomes was
      suggested to be provoked by reactive oxygen species and an origin of
      chemiluminescence was shown to be singlet oxygen.

PMID- 7718303
TI  - Altered urinary porphyrin excretion in a human population chronically exposed to
      arsenic in Mexico.
AB  - 1. A detailed study of the urinary excretion pattern of porphyrins in humans
      chronically exposed to As via drinking water was performed using high performance
      liquid chromatography (HPLC) 2. Thirty-six individuals (15 men and 21 women) were
      selected from a town which had 0.400 mg L-1 of As in drinking water. The control
      group consisted of thirty-one individuals (13 men and 18 women) whose As
      concentration in drinking water was 0.020 mg L-1. 3. The major abnormalities in
      the urinary porphyrin excretion pattern observed in arsenic-exposed individuals
      were: (a) significant reductions in coproporphyrin III excretion resulting in
      decreases in the COPRO III/COPRO I ratio, and (b) significant increases in
      uroporphyrin excretion. Both alterations were responsible for the decrease in the
      COPRO/URO ratio. 4. No porphyrinogenic response was found in individuals with
      urinary As concentrations below 1,000 micrograms of As g-1 of creatinine.
      However, as arsenic concentrations exceeded this value, the excretion of
      porphyrins (except coproporphyrin III) increased proportionally. 5. The
      prevalence of clinical signs of arsenicism showed a direct relationship to both
      As concentration in urine and time-weighted exposure to As. A direct relationship
      between time-weighted exposure and alterations in urinary porphyrin excretion
      ratios was also observed. 6. The alterations found are compatible with a lower
      uroporphyrinogen decarboxylase activity in arsenic-exposed individuals. However,
      the similarities in the urinary porphyrin excretion pattern between As-exposed
      individuals and Dubin-Johnson syndrome patients suggest that impairments in the
      excretion of coproporphyrin isomers may also contribute to the pattern observed.

PMID- 7718304
TI  - Elemental mercury vapour toxicity: treatment and levels in plasma and urine.
AB  - 1. We report two cases of acute mercury vapour intoxication in humans. The
      mercury vapour was released from smelting alloys (gold-mercury amalgam). The
      alloy was apparently contaminated with an unknown amount of mercury. 2. Within
      half an hour of the incident, the victims began having moderate headache, nausea,
      lumbar pain and shortness of breath at rest. The patients were treated with BAL
      (2,3 dimercaptopropanol), followed by DMSA (2,3 dimercaptosuccinic acid). 3.
      Serial measurements of mercury metal in plasma and in urine were made for ten
      days. 4. The results suggest that in spite of the treatment, relatively high
      concentrations of mercury remain in the plasma for a very long time, and this
      could be explained by the progressive release of mercury from red blood cells and
      tissues after oxidation. However, BAL and DMSA did not seem to be the most
      efficient antidotes. They reduce the plasma inorganic mercury uptake at
      concentrations of < 50 micrograms I-1.

PMID- 7718305
TI  - The development of three-dimensional in vitro human tissue models.

PMID- 7718306
TI  - Metabolism and genotoxicity of the halogenated alkyl compound tris(2,3
      dibromopropyl)phosphate.
AB  - 1. The genotoxicity of the flame retardant tris(2,3-dibromopropyl)phosphate (Tris
      BP) was studied in vivo. Results showed that Tris-BP was highly clastogenic, but
      it could only initiate a low number of preneoplastic foci in the rat liver in
      vivo. In Drosophila, Tris-BP could be classified as a cross-linking agent,
      because it was more clastogenic than mutagenic. The use of completely deuterated
      Tris-BP as a metabolic probe revealed that cytochrome P450 and most likely the
      formation of 2-bromoacrolein (2BA) from Tris-BP is important for the observed
      genotoxic effects. 2. In contrast to the high mutagenicity of Tris-BP and 2BA in
      Salmonella typhimurium, we were unable to detect an increase in mutation
      frequency of 2BA on the hprt locus of human TK6 cell line. In another system,
      using a shuttle vector modified with 2BA:DNA-adducts, also no increase in
      mutation frequency could be detected in human cells. This low mutagenicity of 2BA
      corresponds with its low mutagenicity in Drosophila and its low induction of
      preneoplastic foci in the rat liver. 3. Several DNA adducts of 2BA have been
      identified, including an unstable 3-(bromooxypropyl)thymidine adduct which has
      the potential to form cross-links and a cyclic 3,N4-(bromo)propeno-deoxycytidine
      adduct which can possibly be involved in the clastogenicity of Tris-BP. 4. Taken
      together, these data indicate that Tris-BP and 2BA may not effectively induce
      gene mutations in eukaryotic systems, but rather be potent clastogens. Risk
      assessment of these and related compounds should therefore be based on the
      knowledge of clastogens rather than mutagens.

PMID- 7718307
TI  - Biotransformation and toxicity of halogenated benzenes.
AB  - 1. Multiple potentially harmful metabolites can be distinguished in the metabolic
      activation of halogenated benzenes: epoxides, phenols, benzoquinones and
      benzoquinone-derived glutathione conjugates. 2. The role of these (re-) active
      metabolites in the toxic effects induced by halogenated benzenes such as
      hepatotoxicity, nephrotoxicity, porphyria and thyroid toxicity is discussed. 3.
      Evidence is presented suggesting that the formation of reactive benzoquinone
      metabolites rather than the traditional epoxides is linked to halogenated benzene
      induced hepatotoxicity. 4. A crucial role for the benzoquinone-derived
      glutathione adducts in halogenated benzene-induced nephrotoxicity is clearly
      established. 5. Although metabolic activation appears to be involved in
      porphyria, the nature of the ultimate porphyrinogenic metabolite has not been
      elucidated yet. 6. Disturbances in thyroid hormone (and retinoid) homeostasis can
      be (at least partially) explained by the formation of halogenated phenol
      metabolites. 7. In conclusion, for a relevant prediction of the ultimate fate of
      a compound in a living organism, one should know the chemical characteristics and
      reactivity of the parent compound and its metabolites, together with insight into
      the formation mechanism of each of the suspected metabolites, and an
      understanding of the interaction between a specific chemical (reactive) structure
      and its target molecule.

PMID- 7718308
TI  - Cellular and molecular aspects of organotin-induced thymus atrophy.
AB  - 1. Organotin compounds, di-n-butyltin dichloride (DBTC) in particular, have been
      shown to cause thymus atrophy in the rat. 2. DBTC-induced thymus atrophy results
      from a depletion of small CD4+CD8+ thymocytes which is caused by a diminished
      production of immature CD4-CD8+ and CD4+CD8+ thymoblasts. 3. DBTC inhibits the
      activation, but not the differentiation of immature CD4-CD8+ thymocytes in vitro
      and in vivo suggesting a selective antiproliferative activity of DBTC. 4. DBTC
      inhibits the adhesion molecule-mediated binding of thymocytes to thymic
      epithelial cells. 5. DBTC enhances the Ca2+ release elicited by cross-linking of
      the T cell receptor complex (TcR alpha beta-CD3) on thymocytes and moreover
      delays cap formation of the TcR alpha beta-CD3 receptor. 6. It is concluded that
      DBTC possibly interferes with the functioning of the cytoskeleton. The relation
      of the in vitro findings to the inhibition of immature CD4-CD8+ thymocyte
      activation and the induction of thymus atrophy is unknown as yet.

PMID- 7718309
TI  - Molecular dosimetry of DNA damage induced by polycyclic aromatic hydrocarbons;
      relevance for exposure monitoring and risk assessment.
AB  - Polycyclic aromatic hydrocarbons (PAH) form a large group of organic chemicals
      that are widely distributed in our environment as pollutants of air, water and
      soil. Several PAH are carcinogenic in rodents, while exposure to these compounds
      has been associated with various types of human cancer. Upon entering the body,
      PAH may be converted into reactive electrophilic species, which can give rise to
      the formation of DNA adducts. DNA adduct formation is considered to be the
      initial event in chemical carcinogenesis. In this paper, two methods are
      illustrated that are widely used to determine PAH-DNA adduct formation, namely
      32P-postlabelling, and immunochemical analysis with specific antibodies. The
      applications of the 32P-postlabelling assay comprise the following: A study of
      interspecies differences in PAH bioactivation in vitro, with microsomal
      preparations isolated from liver tissue of various rodent species and of human
      origin; the results indicate that there are considerable qualitative differences
      between the adduct patterns obtained, which is relevant with respect to
      extrapolation from animal to man. The analysis of DNA adduct formation in fish
      retrieved from marine environments polluted to various extents with PAH; results
      of these studies show a correlation between liver-DNA adduct levels in these fish
      and the degree of PAH contamination in the aquatic environment. Biomonitoring of
      PAH exposure through analysis of adducts in blood cells obtained from heavy and
      light smokers; the data show a fair correlation between PAH-DNA adduct levels in
      white blood cells and cotinine content in blood plasma, the latter being used as
      a marker for exposure to cigarette smoke.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718310
TI  - Effects of polychlorinated biphenyls (PCBs) and dioxins on growth and
      development.
AB  - Polychlorinated biphenyls (PCBs) and dioxins are potentially toxic compounds
      which occur widely in the environment. Their effects on the growth and
      development of infants at the levels currently found in highly industrialised
      western countries is not well known. This Dutch multicenter study, combining
      animal and human studies, tries to answer this question. Animal studies showed
      that PCB 169, given once during pregnancy at a dose of 1.8 g kg-1 bodyweight, has
      an effect on developmental parameters, dopamine regulation and fertility. Effects
      on thyroid hormones were also found in animals, probably due to both a
      competitive binding of PCB metabolites to the thyroxine binding protein and
      increased glucuronidation. Perhaps to compensate for this, an increased diodase
      activity in the brain was found. Human studies involved 400 mother-infant pairs,
      half of them being breast-fed, the other half were fed a formula devoid of PCBs
      and dioxins. PCB levels were measured in serum and dioxin and PCB levels in
      breastmilk. Levels were found to be as high as previously found in highly
      industrialised countries. Growth and development were carefully documented, but
      no data are as yet available. In pregnant women, a significant negative
      correlation was found between some dioxin and PCB congeners in milk and plasma
      thyroid hormones, while newborn infants showed higher thyroid stimulating hormone
      (TSH) at higher levels of dioxin exposure. In summary, data from this combined
      multicenter study involving animals and humans increases our insight into the
      potentially negative effects of PCBs and dioxins on growth and development.

PMID- 7718311
TI  - Epigenetic puzzle. Zonal heterogeneity of peroxisomal enzymes in rat liver:
      differential induction by three divergent hypolipidemic drugs.

PMID- 7718312
TI  - Should breast feeding mothers give up meat? Metabolism of the food-derived
      carcinogen 2-amino-1-methyl-6-phenyl-imidazo [4,5-b] pyridine by lactating
      Fischer 344 rats and their nursing pups.

PMID- 7718313
TI  - Networks controlling pneumocyte proliferation. Modulation of oncogene and tumor
      suppressor gene expression in a hamster model of chronic lung injury with varying
      degrees of pulmonary neuroendocrine cell hyperplasia.

PMID- 7718314
TI  - Copper-overload causes cancer? The LEC rat: a model for human hepatitis, liver
      cancer, and much more.

PMID- 7718315
TI  - "Megatherapy" for advanced neuroblastoma--rationale and role.

PMID- 7718316
TI  - A randomised study to compare the effect of the luteinising hormone releasing
      hormone (LHRH) analogue goserelin with or without tamoxifen in pre- and
      perimenopausal patients with advanced breast cancer.
AB  - The use of goserelin with or without tamoxifen was investigated in a randomised
      multicentre study involving 318 pre- and perimenopausal advanced breast cancer
      patients. With a median follow-up of 93 weeks, 31% of goserelin-treated patients
      had objective responses (UICC criteria) compared with 38% of goserelin plus
      tamoxifen-treated patients (P = 0.24). There was a modest benefit in favour of
      combination therapy in time to progression (P = 0.03) but not in survival (P =
      0.25). Median follow-up for survival was 117.5 weeks. Median times for disease
      progression and survival were 23 and 127 weeks in the goserelin alone group and
      28 and 140 weeks in the combination group, respectively. In 115 patients with
      skeletal metastases only, significant differences in favour of combination
      therapy were seen in response rate, time to progression and survival. Both
      treatments were well tolerated and no additional safety issues were associated
      with combination therapy.

PMID- 7718317
TI  - Adjuvant intravesical mitoxantrone after transurethral resection of primary
      superficial transitional cell carcinoma of the bladder. A prospective randomised
      study.
AB  - A prospective randomised controlled clinical trial began in 1989 on 126 patients
      with superficial transitional cell carcinoma of the bladder (pTa-pT1, grades 1-3)
      to compare the efficacy of adjuvant topical mitoxantrone after transurethral
      resection versus no further treatment. 62 patients received no further treatment,
      64 patients received weekly 20 mg mitoxantrone intravesically for 6 weeks after
      differentiated TUR of all visible tumours. The endpoint of the study was any
      progression of stage or grade or further recurrences. The median follow up was 29
      months--the minimum follow up was 24 months. The percentage of recurrences (25.8
      versus 23.4), the recurrence rate (1.2 versus 0.9), the overall disease free
      interval and the tumour progression rate showed no statistically significant
      differences (P > 0.05 Mantel-Cox test). Only the comparison of time to recurrence
      in tumours with recurrences showed a statistically significant difference, with a
      longer disease free interval for the TUR plus mitoxantrone group (P = 0.016
      Mantel-Cox test).

PMID- 7718318
TI  - A comparison of polychemotherapy and melphalan/prednisone for primary remission
      induction, and interferon-alpha for maintenance treatment, in multiple myeloma. A
      prospective trial of the German Myeloma Treatment Group.
AB  - 406 untreated multiple myeloma patients of stage I (n = 54), II (n = 148) and III
      (n = 204) were enrolled in the trial. 51/54 stage I and 60/148 stage II patients
      were asymptomatic and followed without treatment until disease progression
      (progression free survival: 60% after 4 years for stage I versus 50% after 1 year
      for stage II). Symptomatic patients of stage I (n = 3/54) and II (n = 88/148)
      presenting with tumour progression, received melphalan 15 mg/m2 intravenously
      (i.v.) and prednisone 60 mg/m2 oral days 1-4 (MP). Stage II disease remission
      rate was 59%, and 50% tumour related survival (TRS) was 59 months. Stage III
      patients were randomised to receive MP or VBAMDex
      (vincristine/BCNU/doxorubicin/melphalan/dexamethasone) treatment. 43% of MP
      treated patients responded compared with 64% of the VBAMDex group. 50% TRS was 36
      months in both groups without a detectable difference. 117 responders of stage II
      and III with stable disease were randomised to receive either IFN-alpha (5 x
      10(6) IU, subcutaneous (S.C.) 3 times per week) or no maintenance treatment. The
      relapse rate in both groups was 50% after 13 months. No survival benefit for IFN
      alpha treated patients was observed (50% TRS: 45 months).

PMID- 7718319
TI  - Psychological reactions in patients with malignant melanoma.
AB  - Psychological and psychosomatic reactions to malignant melanoma were studied,
      comparing patients with tumour thickness < or = 0.8 mm versus > 0.8 mm and
      recurrent versus non-recurrent patients. Gender differences were also studied.
      Consecutive melanoma patients, Stage I (n = 144), were interviewed at their first
      postsurgery follow-up visit to an oncology clinic and completed questionnaires 7
      and 13 months later. The questionnaire contained items regarding interest in
      nevi, sleeping problems, psychosomatic complaints, and the Hospital Anxiety and
      Depression Scale. Patients with a more unfavourable prognosis (tumour thickness >
      0.8 mm), subjected to regular medical procedures, did not differ from those with
      a more favourable prognosis (< or = 0.8 mm), except reporting more sleeping
      problems. Women had considerably higher levels of problems than men. Amongst
      patients with an unfavourable prognosis, those with recurrence within 2 years
      showed lower levels of anxiety at the first visit compared with those free from
      recurrence after 2 years.

PMID- 7718320
TI  - Quality of life in adult cancer patients treated with bone marrow transplantation
      -a review of the literature.
AB  - There is now an increasing interest in measuring quality of life (QOL) in cancer
      patients. Information on psychosocial issues and the patients' QOL give a more
      comprehensive evaluation of the treatment outcome than survival and relapse free
      intervals alone. Bone marrow transplantation (BMT) has become a standard,
      curative treatment in haematological diseases such as leukaemia and lymphomas.
      However, serious physical and psychological side effects are experienced by some
      patients. A review of the literature on QOL in adult BMT patients shows that the
      development in post-BMT research on psychosocial factors is slowly progressing.
      Most studies are retrospective with small sample sizes, and only five of 48
      studies fulfilled our preset quality criteria. Identification of factors that are
      predictive for poor post-BMT outcome might provide a basis for targeted support
      programmes. This underlines the necessity of undertaking prospective studies
      using reliable and well-validated methods for measuring QOL in this patient
      group.

PMID- 7718321
TI  - A randomised study to determine whether routine intravenous magnesium supplements
      are necessary in patients receiving cisplatin chemotherapy with continuous
      infusion 5-fluorouracil.
AB  - Cisplatin is an effective antineoplastic agent, but can cause renal tubular
      damage leading to urinary magnesium wasting and hypomagnesaemia. Cisplatin and 5
      fluorouracil, when used in combination, have synergistic antitumour activity in
      upper gastrointestinal malignancies, but it is unclear whether they have additive
      effects on renal magnesium loss. To determine the optimal regimen for magnesium
      supplementation in these patients, we have conducted a randomised trial of
      routine intravenous magnesium supplements compared with magnesium given on an 'as
      required' basis. 32 patients were randomised to receive magnesium intravenously
      in prehydration and posthydration fluids with cisplatin chemotherapy, or to
      receive magnesium only when the serum level was low. 5-fluorouracil was given as
      a continuous infusion. Serum magnesium was measured on admission for each cycle
      of chemotherapy and an interim measurement performed between each cycle. 28
      patients were evaluable. All patients randomised to receive magnesium on an 'as
      required' basis had at least one episode of hypomagnesaemia. On subsequent
      admissions for chemotherapy (cycles 2 and 3), the mean serum magnesium level was
      significantly lower in these patients compared with patients who received
      magnesium routinely (P < 0.05). After omission of magnesium from the first cycle
      of cisplatin, magnesium supplements were necessary in 50% of subsequent cycles,
      usually by the second or third cycle. Moreover, there were several instances of
      symptomatic hypomagnesaemia requiring further intravenous supplements in mid
      cycle. Patients treated with a combination of cisplatin and 5-fluorouracil should
      be given intravenous magnesium supplements with each cycle of cisplatin
      chemotherapy. Nevertheless, episodes of hypomagnesaemia still occur, and
      additional intravenous supplements may be required, highlighting the importance
      of measuring this electrolyte.

PMID- 7718322
TI  - Epidermal growth factor receptor (EGFr) expression in non-small cell lung
      carcinomas correlates with metastatic involvement of hilar and mediastinal lymph
      nodes in the squamous subtype.
AB  - Epidermal growth factor receptor (EGFr) levels were evaluated in paraffin
      embedded tumour specimens of non-small cell lung cancer (NSCLC) from 176 patients
      who underwent surgical resection. The EGFr expression was evaluated by
      immunocytochemical assay using a monoclonal antibody which recognises the
      external domain of the receptor. EGFr immunoreactivity was significantly higher
      in squamous than in non-squamous cell carcinomas (P = 0.0009). Hilar and/or
      mediastinal nodal involvement was found in 29 of 105 (27.4%) squamous cancers,
      and in this group of patients, the mean of EGFr positive cells was significantly
      higher than that of patients without nodal involvement (P = 0.01). No significant
      correlations were found between the expression of EGFr and other
      clinicopathological or biological parameters such as T-status, grading,
      proliferative activity. EGFR is suggested to represent a useful indicator of
      nodal metastasis in NSCLC.

PMID- 7718323
TI  - Somatostatin receptor imaging of small cell lung cancer (SCLC) by means of 111In
      DTPA octreotide scintigraphy.
AB  - Somatostatin receptors have been described on the membrane of neoplastic cells
      derived from the APUD system and their expression has also been demonstrated on
      small cell lung cancer (SCLC) in vitro and in vivo. 21 patients with SCLC were
      studied using 111In-octreotide (111In-OCT) scintigraphy. Scintigraphic
      examinations were performed following intravenous (i.v.) injection of 111 MBq
      111In-OCT with whole-body scintigraphy and planar scintigraphy of the thorax as
      well as the SPET technique. No short-term side effects were described following
      111In-OCT administration. We studied the 111In-OCT biodistribution in 3 patients
      with serial scintigraphies at 1, 5 and 24 h. We used the 5 h as standard scanning
      time for the following 18 patients. The scintigraphic results were compared with
      those of other conventional diagnostic procedures. 111In-OCT detected 86% (48/56)
      of the lesions already known at the time of scintigraphy. It was positive in all
      20 SCLC patients and negative in one lung adenocarcinoma. 111In-OCT showed high
      sensitivity for mediastinal metastases (94%) and good sensitivity for bone
      metastases (75%) and abdominal lymph node metastases (71%). 111In-OCT did not
      detect two liver metastases. 111In-OCT detected five unknown lesions which were
      confirmed by other diagnostic examinations. 111In-OCT was also effective in
      cancer patients with low levels of NSE. Our study shows that 111In-OCT
      scintigraphy is a reliable, non-invasive technique to detect primary SLCL and its
      locoregional or distant metastases. The clinical utility of receptor status
      characterisation obtained with 111In-OCT scintigraphy should be evaluated by
      means of an appropriate prospective study.

PMID- 7718324
TI  - The mortality rate of the province of birth as a risk indicator for lung and
      stomach cancer mortality among Genoa residents born in other Italian provinces.
AB  - This study analyses the relationship between migration and mortality for lung and
      stomach cancer, these diseases being those considered susceptible to changes in
      environmental conditions and individual habits that usually follow migration.
      Mortality rate of the province of birth was used as the index of risk related to
      migration. Data were analysed using the Poisson regression model for grouped
      data. Results indicate that migration determines modifications in the mortality
      rates of the migrant populations for the diseases under study. For lung cancer,
      the analysis showed a greater risk for migrants originating from areas with high
      rates and that migrants had a reduced risk in comparison with natives of Genoa.
      With regard to stomach cancer, the study revealed that migrants originating from
      high risk areas had higher relative risks than the Genoa natives, even if these
      were lower than expected when compared to the risks of the populations in the
      regions from which the migrants originated.

PMID- 7718325
TI  - Detection by polymerase chain reaction of BCR/ABL transcripts in
      myeloproliferative diseases at time of diagnosis and for monitoring chronic
      myelogenous leukaemia patients after bone marrow transplantation.
AB  - The Philadelphia chromosome t(9;22)(q34;q11) is a cytogenetic marker for chronic
      myelogenous leukaemia (CML), and is also present in some acute leukaemias. The
      translocation in CML gives rise to two BCR/ABL chimeric transcripts (b3a2 and
      b2a2) encoding a 210-kD tyrosine kinase protein. These leukaemia-specific
      transcripts can be detected easily by the reverse transcriptase polymerase chain
      reaction (PCR). PCR has improved the possibility of detecting minimal residual
      leukaemia cells in Ph-positive patients, especially after bone marrow
      transplantation (BMT). With PCR, we looked for BCR/ABL transcripts in 30 patients
      with CML and 4 with essential thrombocythaemia at time of diagnosis, finding a
      significant difference in the platelet counts of CML patients carrying b3a2 or
      b2a2 transcripts. The BCR/ABL transcript was monitored by PCR in 6 CML patients
      after BMT. The usefulness of PCR in clinical practice at time of diagnosis, and
      the biological and clinical significance of positive/negative PCR results, in
      patients with transplants, are discussed.

PMID- 7718326
TI  - Expression of deoxycytidine kinase and phosphorylation of 2-chlorodeoxyadenosine
      in human normal and tumour cells and tissues.
AB  - Deoxycytidine kinase (dCK) activates several clinically important drugs,
      including the recently developed antileukaemic compound 2-chlorodeoxyadenosine
      (CdA). The distribution of dCK in cells and tissues has previously been
      determined by activity measurements, which may be unreliable because of the
      presence of other enzymes with overlapping substrate specificities. Therefore we
      have measured dCK polypeptide levels in extracts of normal and malignant human
      peripheral blood mononuclear cells, gastrointestinal tissues and sarcomas, using
      a specific immunoblotting technique, as well as the phosphorylation of CdA in the
      same extracts. High levels of dCK were found in all major subpopulations of
      normal mononuclear leucocytes (120 +/- 19 ng dCK/mg protein) and in B-cell
      chronic lymphocytic leukaemia (81 +/- 30 ng/mg, n = 23). Hairy-cell leukaemia
      contained lower levels (28 +/- 23 ng/mg, n = 7), as did three samples of T-cell
      chronic lymphocytic leukaemia (18 +/- 14 ng/mg). Phytohaemagglutinin stimulation
      of normal lymphocytes did not lead to any substantial increase in either dCK
      activity or protein expression (less than 2.5-fold). The human CEM wt T
      lymphoblastoid cell line contained 56 +/- 1 ng/dCK/mg protein, while in the CEM
      ddC50 and AraC8D mutants that lack dCK activity, no dCK polypeptide could be
      detected. In colon adenocarcinomas, the dCK content was significantly higher (20
      +/- 9 ng/mg, n = 20) than in normal colon mucosa (8 +/- 3.5 ng/mg, n = 19, P <
      0.05). A similar pattern of dCK expression was found in gastric adenocarcinomas
      (21 +/- 13 ng/mg, n = 5) and normal stomach mucosa (6 +/- 5 ng/mg, n = 5, P <
      0.15). One leiomyosarcoma and one extra-skeletal osteosarcoma showed dCK levels
      comparable with those found in normal lymphocytes (84 +/- 6 and 109 +/- 4 ng/mg,
      respectively), while other sarcoma samples contained lower levels, comparable to
      the gastrointestinal adenocarcinomas (20 +/- 7 ng/mg, n = 12). Thus, dCK is
      expressed constitutively and predominantly in lymphoid cells, but it is also
      found in solid non-lymphoid tissues, with increased levels in malignant cells.
      The phosphorylation of CdA in crude extracts showed a close correlation to the
      dCK polypeptide level.

PMID- 7718327
TI  - Formation of cytosine arabinoside-5'-triphosphate in different cultured
      lymphoblastic leukaemic cells with reference to their drug sensitivity.
AB  - The accumulation of intracellular cytosine arabinoside-5'-triphosphate (Ara-CTP)
      is determined in five lymphoblastic cell lines: Molt 4, H9 and three newly
      established cell lines from paediatric patients, KFB-1, KFB-2, KFT-1. The cell
      lines KFB-1 and KFB-2 are B-lymphoblastic (B-ALL), the others are T-lymphoblastic
      leukaemic cells (T-ALL). The Ara-CTP levels were compared with the sensitivity of
      the cells to Ara-C. The cells were incubated at different concentrations (100 nM
      100 microM) of Ara-C for 4 h or incubated for variable times (30 min-11 h) at
      0.1, 1 and 10 microM Ara-C to form Ara-CTP. The Ara-CTP-concentrations were
      measured by high pressure liquid chromatography (HPLC). To determine the
      sensitivity of the cells to Ara-C, the MTT colorimetric-assay was used. The
      studies indicate that different B- and T-lymphoblastic leukaemia cell lines
      accumulate Ara-CTP to a markedly different extent. Ara-CTP plateau levels and
      sensitivity of the cells to Ara-C correlated well in four of the five cells lines
      studied.

PMID- 7718328
TI  - Primary sequence determination and molecular modelling of the variable region of
      an antiMUC1 mucin monoclonal antibody.
AB  - Polymerase chain reaction (PCR) products representative of the DNA sequence
      coding for the variable heavy (VH) and the variable light (VL) chains of an
      antiMUC1 mucin monoclonal antibody, C595, have been produced. These products were
      cloned, sequenced, and the primary amino acid sequences of the VH and VL regions
      deduced. The hypervariable complementarity determining regions (CDRs) and
      framework regions in the heavy and light chains were located, and homologies with
      canonical forms for the CDR loops L1, L2, L3, H1 and H2 were identified by
      database searching. The structure for the H3 loop was calculated directly.
      Computational molecular modelling was accomplished using the fully automated AbM
      package (Oxford Molecular, Oxford, U.K.). Energy minimisation was performed using
      the program InsightII (Biosym, San Diego, California, U.S.A.). The investigation
      provides a basis for the molecular analysis of the antigen binding site of the
      C595 antibody with the aim to identify key residues and interactions involved in
      the immune recognition of the C595 antibody defined epitope, which is expressed
      in the majority of breast and ovarian carcinomas.

PMID- 7718329
TI  - Clonal dominance between subpopulations of mixed small cell lung cancer
      xenografts implanted ectopically in nude mice.
AB  - Clonal evolution of neoplastic cells during solid tumour growth leads to the
      emergence of new tumour cell subpopulations with diverging phenotypic
      characteristics which may alter the behaviour of a malignant disease. Cellular
      interaction was studied in mixed xenografts in nude mice and during in vitro
      growth of two sets of small cell lung cancer (SCLC) subpopulations (54A, 54B and
      NYH, NYH2). The tumour cell lines differed in cellular DNA content enabling flow
      cytometric DNA analysis (FCM) to be used to monitor changes in the fractional
      composition of the mixed cell populations. The progeny clone 54B was found to
      dominate the parent 54A clone when grown as mixed subcutaneous xenografts in nude
      mice, whereas no dominance was exerted during in vitro growth. The in vivo
      dominance could not be explained by differences in growth kinetics between the
      two tumour cell lines, and the interaction was not dependent on 54B being in
      excess in mixed tumours. The dominance was dependent on close in vivo contact as
      no remote effect on the growth of 54A was found when the dominating 54B cells
      were growing in the opposite flank of tumour-bearing mice. Irradiation
      inactivated 54B cells were unable to exert the dominating effect, indicating that
      the interaction required viable and proliferating cells. Clonal dominance was not
      found in mixed NYH-NYH2 tumours indicating that the dominance mechanism(s) may
      not always be operational between subpopulations in heterogeneous tumours.
      Recognition of interaction between tumour cell populations may result in a better
      understanding of the behaviour of heterogeneous human malignancies.

PMID- 7718330
TI  - Resistance mechanisms determining the in vitro sensitivity to paclitaxel of
      tumour cells cultured from patients with ovarian cancer.
AB  - Paclitaxel, a drug which stabilises microtubules, demonstrates marked activity
      against ovarian cancer. We investigated the sensitivity to paclitaxel of tumour
      cells from disaggregated solid tumours or tumour-bearing ascites from 7 ovarian
      cancer patients, and 21 established tumour cell lines (ovarian, melanoma and
      lung). Response was quantitated by [3H]-thymidine incorporation in 96-well plates
      or by colony growth. Dose-response curves to paclitaxel were biphasic with a dose
      dependent phase providing an IC50 value (50% reduction in incorporation) and dose
      dependent "plateau" phase where the effect was independent of paclitaxel
      concentration. IC50 values ranged from 2.5 to 110 nM with evidence of multidrug
      resistance in the two most resistant cell lines. The "plateau" killing values
      varied from 0.1 log10 to > 3.4 log10 units reduction, and were found to be
      significantly correlated (r = 0.86; P < 0.0001) with logarithmic culture doubling
      times of the cell lines. Cellular glutathione levels were measured and found not
      to be significantly associated with response to paclitaxel. The results suggest
      that the ratio of paclitaxel exposure time to the culture doubling time is a
      major factor in paclitaxel cytotoxicity. The relationship between tumour cell
      cytokinetics and paclitaxel pharmacokinetics in vivo may therefore be crucial in
      determining clinical paclitaxel response.

PMID- 7718331
TI  - Growth regulation by all-trans-retinoic acid and retinoic acid receptor messenger
      ribonucleic acids expression in gastric cancer cells.
AB  - Retinoic acid has been recognised as a pivotal compound in cell differentiation,
      proliferation and malignant transformation. We investigated the effects of all
      trans-retinoic acid on cell growth and the expression of retinoid nuclear
      receptor mRNAs in gastric cancer cells in vitro. Cell growth was quantified by
      measuring total cellular DNA. The growth of two of the five gastric cancer cell
      lines tested (SC-M1 and TSGH9201) was inhibited by all-trans-retinoic acid at
      concentrations ranging from 1 x 10(-8) M to 1 x 10(-6) M. Growth inhibition was
      associated with G0/G1 phase arrest as determined by flow cytometric analysis.
      Northern blot analysis showed that all five cell lines expressed mRNA for
      retinoic acid receptors alpha and retinoic x receptor alpha and beta. Retinoic
      acid receptor beta mRNA was only expressed in TSGH9201 and TMK-1 gastric cancer
      cell lines. Two RAR gamma mRNA transcripts (3.2 and 3.0 kb) were detected in SC
      M1 and TSGH9201 cells. RA-resistant cells had markedly decreased levels of the
      3.2 kb RAR gamma transcript. All-trans-retinoic acid had a cytostatic effect on
      the growth of some gastric cancer cells, which may be associated with the
      expression of retinoic acid receptors.

PMID- 7718332
TI  - Effects of suramin on human lung cancer cell lines.
AB  - Suramin cytotoxicity was studied in a panel of human lung cancer cell lines by
      the MTT assay. The concentrations of suramin which induced 50% growth inhibition
      (IC50) ranged from 130 to 3715 microM for the cell lines growing in medium
      containing 10% fetal calf serum (FCS). In only one cell line was the IC50 at a
      concentration that can be reached in plasma of patients treated with suramin.
      Suramin was 18 and 3.3 times more cytotoxic on NCI-N417 cells growing in 2% FCS
      and in HITES serum-free medium, respectively, than growing in 10% FCS. No
      difference in suramin cytotoxicity was observed between small and non-small cell
      lung cancer cell lines. At the lower concentrations tested, suramin stimulated
      proliferation of the two small cell lung cancer cell lines, NCI-H187 and NCI
      N417. Of several growth factors tested, none induced stimulation of growth in NCI
      H187 and NCI-N417 cell lines, nor did they in any way alter the stimulatory
      effect of suramin. Cell counting, DNA flow cytometric analysis and Ki-67 staining
      confirmed a higher proliferative state in suramin-exposed NCI-H187 cells as
      compared with untreated cells. However, topoisomerase II-alpha gene expression
      remained unchanged, as assessed by northern blot analysis and immunostaining.
      Suramin had an inhibitory effect on topoisomerase II activity, as assessed by the
      kDNA decatenation assay, with an IC50 of approximately 40 microM. In conclusion,
      suramin has significant cytotoxic activity in a minority of human lung cancer
      cell lines, and it stimulates proliferation in some instances. The pleiotropic
      action of suramin observed should caution on the possibility of tumour
      acceleration in patients being treated with this drug.

PMID- 7718333
TI  - Multi-modality megatherapy with [131I]meta-iodobenzylguanidine, high dose
      melphalan and total body irradiation with bone marrow rescue: feasibility study
      of a new strategy for advanced neuroblastoma.
AB  - New therapeutic approaches are needed for advanced neuroblastoma as few patients
      are currently curable. We describe an innovative strategy combining [131I]meta
      iodobenzylguanidine ([131I]mIBG) therapy with high dose chemotherapy and total
      body irradiation. The aim of combining these treatments is to overcome the
      specific limitations of each when used alone to maximise killing of neuroblastoma
      cells. Five children received combined therapy with [131I]mIBG followed by high
      dose melphalan and fractionated total body irradiation. Autologous bone marrow
      transplantation was undertaken in 3 patients and allogeneic in 2 patients. One
      patient received additional localised radiotherapy to residual bulk disease. One
      patient is alive without relapse 32 months after treatment. 4 patients relapsed
      after remissions of 9, 10, 14 and 21 months. These results indicate that this
      combined modality approach is feasible and safe, but further evaluation is
      necessary to establish whether it has advantages over conventional megatherapy
      using melphalan alone.

PMID- 7718334
TI  - A new 123I-MIBG whole body scan scoring method--application to the prediction of
      the response of metastases to induction chemotherapy in stage IV neuroblastoma.
AB  - A new semi-quantitative scoring system is proposed, especially designed for the
      comparative interpretation of sequential whole-body meta-iodo-benzyl-guanidine
      (MIBG) scans in stage IV neuroblastoma children. This method was applied to
      assess whether MIBG scan at mid-course of induction chemotherapy could predict
      the final response. 27 newly diagnosed children were investigated by three
      sequential 123I-MIBG scans performed at the beginning, at mid-course (6 weeks)
      and at the end of neoadjuvant chemotherapy (12 weeks). Whole body scans were
      divided into nine regions in which the extension of bone metastases was
      separately quoted (score range: 0-3). The overall absolute scores were obtained
      by adding the scores of the nine regions. Relative scores were calculated by
      dividing the absolute score at each time by the corresponding pretreatment score.
      The score at mid-induction correctly predicted the overall response of metastases
      at the end of induction (P < 0.0001) in most cases. This method is easy to use,
      reproducible, subject to little inter-investigator variation, and thus well
      adapted to multicentric trials.

PMID- 7718335
TI  - A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in
      patients with neuroblastoma.
AB  - 9 patients with stage IV neuroblastoma were treated with 19 courses of
      human/mouse chimeric monoclonal antiganglioside GD2 antibody ch14.18 at dose
      levels of 30, 40 and 50 mg/m2/day for 5 days per course. The maximum tolerated
      dose (MTD) per injection was 50 mg/m2/day. 7 patients received more than one
      course of treatment, and none revealed any human anti-mouse antibody (HAMA)
      response. Clinical side-effects of patients treated with ch14.18 were abdominal
      and joint pains, pruritus and urticaria. One patient presented with a transient
      pupillatonia, while 2 others showed a unilateral atrophy of the optical nerve
      that was probably attributable to prior therapies. A complete remission was seen
      in 2 patients, partial remission in 2 patients, a minor response in 1 patient and
      stable disease in 1 patient. 3 patients showed tumour progression. Thus, our
      results indicate that treatment with chimeric MAb ch14.18 can elicit some
      complete and partial tumour responses in neuroblastoma patients.

PMID- 7718336
TI  - Fanconi anaemia research: current status and prospects.
AB  - Fanconi anaemia (FA) is an autosomal recessive disease featuring diverse clinical
      symptoms in addition to chromosomal instability and hypersensitivity to
      crosslinking agents. The much increased risk of FA patients developing leukaemia
      and squamous cell carcinomas makes FA an important model disease for cancer
      predisposition. Studies documenting the characteristics of FA cells and their
      response to environmental toxins have failed thus far to disclose the basic
      cellular process that is primarily disturbed in FA cells. Complementation
      analysis suggests that mutations in at least four different genes can cause FA
      (complementation groups FA-A to FA-D). The cDNA for FA-C has been cloned and
      found to encode a novel protein that localises to the cytoplasmic compartment of
      cells. Even though the protein's function is still unknown at present, research
      has now reached the point from where rapid progress to a detailed understanding
      of this syndrome may be foreseen.

PMID- 7718337
TI  - Quality assurance in breast cancer screening cytology: a review of the literature
      and a report on the U.K. national cytology scheme.
AB  - The National Breast Screening Programme in the United Kingdom has had an external
      quality assessment (EQA) scheme for breast screening histopathology since 1990.
      Recently, it was decided, by the Cytology sub-group of the National Co-ordinating
      Committee for Breast Screening Pathology, to institute two forms of cytology
      quality assurance. An EQA scheme is planned with circulation of slides to
      pathologists, but this involves extra time and effort from the participants at a
      time when general pathology workloads are high. Because of this, a computer
      routine has been written to analyse the data already present within the National
      Breast Screening Computer Systems, to enable the calculation of sensitivity and
      specificity of fine needle aspiration, correlating the cytology results with
      subsequent histology or follow-up mammography for lesions where no biopsy is
      performed. This routine uses standardised terminology and calculations and,
      therefore, inter-unit comparisons can be made. Where problems are identified
      within a unit, the Quality Assurance team can investigate the cause and institute
      appropriate measures to correct the problem. This article details the procedures
      involved in this audit and reviews the literature, recalculating the parameters
      in a standard manner for a number of publications. The results of the cytology
      quality assurance routine from seven screening units in one health region in the
      U.K. are presented and the measures taken to improve the level of service are
      discussed.

PMID- 7718338
TI  - Prognostic factor clustering in breast cancer: biology or chronology?

PMID- 7718339
TI  - Circumvention of doxorubicin-resistance in tumours by albumin-conjugated
      doxorubicin.

PMID- 7718341
TI  - Choice over change.

PMID- 7718340
TI  - Hereditary breast cancer in 19 females and 2 males: Kindred, P.G. 1940.

PMID- 7718342
TI  - Homelessness and political will--a professional perspective.

PMID- 7718343
TI  - Derbyshire thirteen working together.
AB  - A group of 13 practices from Derbyshire saw the QDAs as a chance to improve upon
      their total service quality. Working in groups, and with their FHSA, they
      succeeded in improving their service and empowering their practice teams.

PMID- 7718344
TI  - Behind the scenes at Baltimore.

PMID- 7718346
TI  - Flaming disaster?

PMID- 7718345
TI  - Electrical resistance measures for the diagnosis of occlusal caries.

PMID- 7718347
TI  - Memories of fluoridation.

PMID- 7718348
TI  - Water fluoridation and dental health.

PMID- 7718349
TI  - Dental erosion.

PMID- 7718350
TI  - Munchausen's syndrome.

PMID- 7718351
TI  - Munchausen's syndrome.

PMID- 7718352
TI  - Bleeding sockets and casualty departments.

PMID- 7718353
TI  - The invisible women in dentistry.

PMID- 7718354
TI  - West Midlands VTs trainee's prize.

PMID- 7718355
TI  - Coenzyme Q10 and periodontal treatment: is there any beneficial effect?
AB  - Many dentists have been surprised by recent media claims of periodontal benefits
      with a purportedly revolutionary dietary supplement. The research literature on
      coenzyme Q10's periodontal effects does not extend to the international English
      language dental literature, which perhaps explains the surprise. A review of the
      available literature does not give any ground for the claims made, and selected
      papers are discussed to show that there is actually some evidence that coenzyme
      Q10 has no place in periodontal treatment.

PMID- 7718356
TI  - Occupational stress and dentistry: theory and practice. Part I. Recognition.
AB  - Dental practice has been considered to be the most stressful of the health care
      professions. Increasingly dentists in general practice seem to experience more
      physical and mental ill health compared with other health professionals and this
      has been recognised to be a consequence of occupational stress. Occupational
      stress has been related to changes in clinical dental practice with many of the
      perceived causes being within the dentist's own control. Since dentists are faced
      daily with these potential occupational stressors one way of controlling stress
      is through its recognition. This paper highlights experiences common to all those
      in dental practice as a first step in reducing occupational stress.

PMID- 7718357
TI  - Occupational stress and dentistry: theory and practice. Part II. Assessment and
      control.
AB  - Since dentistry has been identified as being a stressful profession, dentists,
      with the help of the members of the dental team, must attempt to achieve a
      relatively stress-free working environment. In addition to recognising potential
      occupational stressors it is important for dentists to be able to assess their
      emotional responses to the practice of dentistry and to arrange their daily
      working lives in such a way as to reduce occupational stress. This paper examines
      the means by which dentists may assess occupational stress as well as person
      centred and/or situation-centred strategies of coping with and controlling
      occupational stress in general dental practice.

PMID- 7718358
TI  - Abnormal anterior siting of the incisive papilla with bilateral patent
      nasopalatine ducts.

PMID- 7718359
TI  - Periodontology: a clinical approach. 2. Periodontal diagnosis and prognosis.

PMID- 7718360
TI  - Clinical decision making--an art or a science? Part V: Patient preferences and
      their influence on decision making.
AB  - Part IV of this series introduced the idea that the value a patient places on an
      outcome has an important influence on the decision making process. This article
      considers this concept further. It argues that dentists should assess a patient's
      preferences and consider these before deciding on a treatment option. The article
      explains that by enumerating all the treatment options and possible outcomes, it
      is possible to assess the value placed on each result. Similarly an assessment is
      crucial if the dentist aims to achieve the optimum treatment result--one which is
      regarded as the most favourable outcome by the patient.

PMID- 7718361
TI  - Attachment of adult rat cardiomyocytes (ARC) on laminin and two laminin
      fragments.
AB  - Adult rat cardiomyocytes (ARC) were cultivated on five different substrates:
      gelatin, fibronectin, laminin-nidogen complex (laminin), the E8 laminin fragment,
      and the E1 laminin fragment. Comparative cell attachment assays have shown that
      ARC prefer adhesion to E8 laminin fragment and laminin. It were shown by video
      time-lapse (VTL) studies that, during the redifferentiation process of ARC in
      culture, the morphology of ARC grown on laminin, fibronectin, and gelatin is
      indistinguishable, whereas the size of ARC grown on the E8 fragment is larger,
      and when grown on the E1 fragment definitely smaller than ARC on the whole
      laminin protein. Immunostaining for vinculin combined with reflection contrast
      microscopy were used to visualize the focal contacts of ARC on these substrates.
      Quantitative measurements, done with the help of a test line system, show that
      the lengths of adhesion plaques/micron2 on gelatin, fibronectin, and laminin are
      about the same. On the E8 fragment more attachment sites/micron2 and on the E1
      fragment fewer attachment sites/micron2 were counted than on whole laminin
      protein. This suggests that substrates influence the number of focal contacts.
      Correlating these results with the observations made in the VTL recording system,
      one can suggest that the length of adhesion sites/micron2 increases in very flat
      and large cells.

PMID- 7718362
TI  - The 1.5-nm projection structure of HeLa cell prosome-MCP (proteasome) provided by
      two-dimensional crystals.
AB  - We grew two-dimensional crystals of HeLa cell prosomes, also called
      multicatalytic proteinases (MCP) and proteasomes, for a structure determination
      by electron microscopy. The molecules were arranged in side views in these
      crystals. The crystals have p21 plane group symmetry with one particle per unit
      cell. This symmetry confirms previously published evidence indicating that
      eukaryotic prosome-MCPs are dimers of two identical halves. Structure factors
      from six crystals each comprising more than 1000 unit cells were combined to
      generate a 1.5-nm projection map. We discovered that while the general
      cylindrical shape of HeLa prosome-MCPs resembles the shape of the archaebacterial
      Thermoplasma acidophilum proteasomes, the internal structure differs
      significantly. We propose that because of different subunit composition, the
      architecture of HeLa prosome-MCPs differs from the basic architecture of related
      particles previously reported.

PMID- 7718363
TI  - Visualization of actin filaments in keratocyte lamellipodia: negative staining
      compared with freeze-drying.
AB  - Depending on the method of preparation, the actin-rich lamellipodia of motile
      cells can show very different structural organizations. This situation has been a
      main contributor to differences in current ideas about the possible mechanisms of
      cell movement. We have here analyzed the structure of the lamellipodium in whole
      mount cytoskeletons using one of the most rapid of crawling cells, the fish
      keratocyte, employing two procedures considered least damaging to actin filament
      arrays: freeze-drying and negative staining. At the front of the lamellipodium,
      where filaments density is the highest, freeze-dried images conveyed the
      impression of a cross-linked network of very short, interconnected filaments--as
      previously observed by others--whereas the same regions appeared as a diagonal
      meshwork of long, more or less straight filaments after negative staining. In
      general, the linearity of actin filaments was not preserved after freeze-drying,
      except in situations where the filaments had partially dried down onto the
      substrate before freezing. In the mid and posterior regions of the lamellipodium
      the actin filaments appeared to be up to several micrometers long by negative
      staining, whereas their length was impossible to discern by freeze-drying, owing
      to filament kinking and aggregation and to the nature of the contrasting
      procedure, which reveals only the upper layers of filaments. We conclude that
      while freeze-drying preserves the overall three-dimensional structure of the
      lamellipodium it also introduces fine-structural distortions in actin that
      obscure actin filament order. Drying in negative stain appears to stabilise the
      actin network.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718365
TI  - Tramadol.

PMID- 7718364
TI  - Paramyosin polarity in the thick filament of molluscan smooth muscles.
AB  - Paramyosin is the main structural component of the thick filament of molluscan
      smooth muscles. These filaments consist of a large paracrystalline core of
      paramyosin with myosin arranged on its surface. The detailed molecular packing of
      paramyosin in the core and the array of myosin on the surface of the paramyosin
      core remain unknown. An unsolved problem is the polarity of the paramyosin
      molecules within these thick filaments (i.e., it is not known whether the
      paramyosin molecules assemble with their NH2-terminal ends pointing toward the
      center or toward the end of the thick filament). Here a method to distinguish
      between the NH2- and the COOH-terminal ends of the paramyosin molecule by
      electron microscopy is described and used to determine their polarity in
      synthetic paracrystalline arrays. This method consists of labeling the cysteine
      residues of paramyosin molecules with the avidin-biotin system developed by Sutoh
      et al. (1984). Accordingly, the sulfhydryl groups of paramyosin--isolated from
      the anterior byssus retractor muscle (ABRM) of Mytilus edulis--were modified with
      maleimide-biotin, and the biotinylated thiols were visualized in the electron
      microscope after glycerol spraying/rotary metal shadowing by attaching monomeric
      avidin to them. Avidin-biotin labeling of the native molecule and its
      carboxypeptidase fragments revealed that ABRM paramyosin contains one pair of
      cysteine at its NH2-terminal end and one pair at approximately 30 nm from its
      COOH-terminal end. Synthetic paracrystalline arrays of paramyosin with known
      axial arrangement were also labeled with the avidin-biotin system. The location
      of the bound avidin in these paracrystals indicated the polarity of paramyosin in
      these arrays. The polarity was also determined by comparison of the transverse
      band-like staining pattern of paracrystals of alpha-paramyosin (intact protein)
      and beta-paramyosin (a proteolytically cleaved alpha-paramyosin that has lost a
      small segment at its COOH-terminal end). Both methods revealed that paramyosin
      assembles with its NH2-terminal end pointing toward the center of the
      paracrystals. The implications of this result for the polarity of paramyosin in
      the native filament core, and for the arrangement of myosin on the surface of
      molluscan thick filaments, are discussed.

PMID- 7718366
TI  - Value of routine preoperative tests: a multicentre study in four general
      hospitals.
AB  - We have assessed the value of routine preoperative tests in asymptomatic patients
      and their influence on anaesthetic and surgical decisions. We studied 3131 ASA I
      and II patients from four general hospitals undergoing elective surgical
      procedures. A retrospective review of the medical records revealed that 853 (27%)
      patients had some abnormal test result, of which 465 (15%) were previously
      unknown and not suspected at the preanaesthetic visit; these comprised 8.6% chest
      radiographs, 5.6% electrocardiograms and biochemical tests, and 2.9%
      haematological tests. Perioperative management was altered in only 0.56-0.26% of
      patients, depending on the particular test. The present study confirms the need
      for selective and rational ordering of preoperative tests, the basis of which
      should be the clinical assessment during the preanaesthetic visit.

PMID- 7718367
TI  - Normal postoperative gastric emptying after orthopaedic surgery with spinal
      anaesthesia and i.m. ketorolac as the first postoperative analgesic.
AB  - We have assessed the effect of i.m. ketorolac or morphine on early postoperative
      gastric emptying of liquids in patients undergoing orthopaedic surgery with
      spinal anaesthesia. Liquid gastric emptying was measured by absorption of
      paracetamol with patients acting as their own controls. There was no delay after
      ketorolac 30 mg, but morphine 10 mg resulted in marked delay. There was no
      difference in postoperative visual analogue pain scores between treatments.

PMID- 7718368
TI  - Comparison of ropivacaine and bupivacaine in extradural analgesia for the relief
      of pain in labour.
AB  - Forty women having requested extradural analgesia for labour were allocated
      randomly to receive 0.5% ropivacaine or bupivacaine 10 ml as the main dose. When
      a top-up was requested, 0.25% ropivacaine or bupivacaine 10 ml was given (the
      same drug as the main dose). The study ended when a second top-up was requested
      or delivery of the baby occurred. Pain from two contractions was assessed before
      extradural block by visual analogue scoring and thereafter with every
      contraction. Sensory block and motor block were assessed at intervals. The only
      significant difference between the groups was a shorter onset of pain relief
      after the main dose of bupivacaine; there were no other significant differences
      in duration, onset of pain relief after top-up, quality of analgesia, spread of
      sensory block and motor block between the groups. Cardiovascular changes and
      neonatal outcome were similar in the two groups.

PMID- 7718369
TI  - Psychological adjunct to perioperative antiemesis.
AB  - In a prospective, randomized study, we have examined the effects of preoperative
      and preinduction positive suggestion on postoperative emetic sequelae. A total of
      226 patients were allocated randomly to receive either positive suggestions or no
      suggestions. Those patients in the positive suggestion group were told before
      operation and on induction of anaesthesia that postoperative emetic sequelae
      would be greatly reduced by the use of two antiemetic drugs. Control patients
      were simply asked to participate in a study of postoperative well being with no
      mention of nausea or vomiting. Nausea, vomiting or retching, and antiemetic
      administration were measured in the first 24 h after operation. Antiemetic
      administration in the positive suggestion group was 16.5% less than in the
      control group (P = 0.03) but there was no significant difference between the
      groups in nausea or vomiting-retching.

PMID- 7718370
TI  - Psychological characteristics and the effectiveness of patient-controlled
      analgesia.
AB  - We have evaluated the level of state and trait anxiety, neuroticism, extroversion
      and coping style as predictors of the effectiveness of patient-controlled
      analgesia (PCA) in 110 patients undergoing total abdominal hysterectomy. After
      operation patients were allocated to receive pain control with either PCA or i.m.
      injections (IMI). Pain was assessed using the short form McGill pain
      questionnaire at 6, 18 and 24 h after operation, and by recording the amount of
      analgesic consumed in the first 24 h after surgery. Both state anxiety and coping
      style were significant predictors of postoperative pain, irrespective of the
      method of analgesia used. Patients using PCA experienced significantly better
      pain control than those receiving IMI. However, it was those with high levels of
      state anxiety who experienced the greatest reduction in pain with PCA. In
      addition to achieving better pain control, patients who received PCA used
      significantly less analgesia and were discharged earlier than patients who
      received IMI.

PMID- 7718372
TI  - Tracheal tube cuff pressure during cardiac surgery using cardiopulmonary bypass.
AB  - To determine the effects of cardiopulmonary bypass (CPB) on tracheal cuff
      pressure, we have measured intracuff pressure (ICP) in 29 consecutive patients
      undergoing cardiac surgery with CPB. Premedication comprised hyoscine and, after
      induction of anaesthesia with diazepam and fentanyl, followed by vecuronium, the
      trachea was intubated using a Portex Profile tracheal tube. Anaesthesia was
      maintained with high-dose fentanyl and 100% oxygen. ICP was measured with a
      transducer and the ICP was adjusted to 20 mm Hg. CPB was used with mild to deep
      hypothermia and blood-gas tensions were regulated according to alpha-stat
      (temperature uncorrected) pH management. Before CPB, ICP was significantly
      reduced from the mean baseline value of 20 (SEM 0.2) to 16.7 (0.6) mm Hg (P <
      0.01). ICP changed significantly during CPB, decreasing to 8.0 (1.0) mm Hg before
      rewarming (P < 0.01 vs immediately before CPB) and increasing to 17.0 (0.6) mm Hg
      after the start of rewarming (P < 0.01 vs before rewarming). After CPB, ICP did
      not differ significantly from that immediately before CPB. We conclude that the
      decrease in ICP during the hypothermic phase of CPB may protect the tracheal
      mucosa against hypotensive ischaemic injury.

PMID- 7718371
TI  - Dobutamine-induced dissociation between changes in splanchnic blood flow and
      gastric intramucosal pH after cardiac surgery.
AB  - Gastric intramucosal acidosis, a sign of splanchnic tissue hypoxia, is common
      after cardiac surgery. We tested the hypothesis that an increase in splanchnic
      blood flow induced by dobutamine improves splanchnic tissue oxygenation after
      cardiac surgery. We measured changes in gastric intramucosal pH, splanchnic blood
      flow and oxygen transport in response to increased systemic flow induced by
      dobutamine (mean 4.4 (range 3.0-7.0) micrograms kg-1 min-1) after coronary artery
      bypass. We studied 22 stable postoperative patients who were allocated randomly
      to receive dobutamine (n = 11) or to serve as controls (n = 11). Dobutamine was
      given also to a separate group with a low cardiac index after operation (n = 6).
      The end-point was to increase cardiac index by at least 25% and to exceed 2 litre
      min-1 m-2. Dobutamine consistently increased mean splanchnic blood flow (control
      0.6 (SD 0.2) vs 0.7 (0.2) litre min-1 m-2 (P < 0.05); normal cardiac output and
      dobutamine 0.7 (0.2) vs 1.1 (0.4) litre min-1 m-2 (P < 0.01); low cardiac output
      and dobutamine 0.4 (0.1) vs 0.7 (0.1) litre min-1 m-2 (P < 0.05)) and oxygen
      delivery (control 102 (29) vs 111 (28) ml min-1 m-2 (ns); normal cardiac output
      and dobutamine 106 (27) vs 156 (47) ml min-1 m-2 (P < 0.01); low cardiac output
      and dobutamine 75 (21) vs 110 (26) ml min-1 m-2 (P < 0.05)) but had no effect on
      splanchnic oxygen consumption (control 44 (10) vs 49 (10) ml min-1 m-2 (ns);
      normal cardiac output and dobutamine 45 (12) vs 51 (17) ml min-1 m-2 (ns); low
      cardiac output and dobutamine 37 (9) vs 40 (9) ml min-1 m-2 (ns)).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7718373
TI  - Effect of cardiopulmonary bypass on hand and forearm blood flow.
AB  - We have assessed the relationship between the aorto-radial pressure difference at
      the conclusion of cardiopulmonary bypass and blood flow to the hand. Hand blood
      flow was estimated from the difference between forearm blood flow measured
      without and with exclusion of the hand circulation. On the same hand, the skin
      temperature on the palm and on the middle finger was recorded, with the amplitude
      of the finger pulse oximeter trace. The aorto-radial pressure difference, after
      cardiopulmonary bypass, correlated with hand blood flow (r = 0.59, P = 0.002).
      There was a significant (P < 0.0001) palm-finger temperature gradient before and
      after cardiopulmonary bypass. In conclusion, while the mean aorto-radial pressure
      difference after bypass results from increased hand blood flow, the finger is not
      a reliable site to assess the state of the systemic circulation, before or after
      cardiopulmonary bypass.

PMID- 7718374
TI  - Post-tetanic burst: a new monitoring method for intense neuromuscular block.
AB  - A new stimulation pattern for evaluation of intense neuromuscular block (post
      tetanic burst (PTB)) was compared with post-tetanic twitch (PTT) during
      spontaneous recovery from vecuronium-induced neuromuscular block. Thirty adult
      patients were allocated to two equal groups and we measured times from
      administration of vecuronium 0.1 mg kg-1 to return of PTB and PTT responses, and
      evoked responses to PTB and PTT stimuli. For PTB stimulation, a 50-Hz tetanus was
      applied at 50 mA for 5 s, and after a pause of 3 s, a 50-Hz burst stimulation was
      applied, consisting of three impulses at 50 mA. PTB stimuli were delivered every
      5 min. Similarly, PTT consisted of a tetanus, a 3-s pause and one single twitch
      stimulation repeated every 5 min. Time to return of the PTB response was
      significantly shorter than that of PTT (mean 23.7 (SD 7.9) compared with 30.7
      (7.0) min) (P = 0.0160), although evoked responses to PTB did not differ
      significantly from those of PTT throughout recovery from vecuronium-induced
      neuromuscular block. This study suggested that PTB was more sensitive in
      evaluating intense neuromuscular block than PTT.

PMID- 7718375
TI  - Cerebrovascular response to carbon dioxide during sodium nitroprusside- and
      isoflurane-induced hypotension.
AB  - We have examined the cerebrovascular response to carbon dioxide during
      normotension, sodium nitroprusside (SNP)-induced hypotension and high dose
      isoflurane-induced hypotension in 10 patients who received a standardized general
      anaesthetic. Carbon dioxide reactivity was determined by varying PaCO2 between
      3.0 and 8.0 kPa and recording simultaneously blood flow velocity from the middle
      cerebral artery (vmca). The paired vmca-PaCO2 data were analysed using linear
      regression to determine carbon dioxide reactivity. During hypotension, both high
      dose isoflurane and SNP reduced significantly mean absolute (from 17.4 (SEM 2.3)
      to 13.0 (1.7) and 8.8 (1.3) cm s-1 kPa-1, respectively; P < 0.05) and relative
      (from 32.5 (3.8) to 23.6 (2.0) and 15.5 (1.3)% kPa-1, respectively; P < 0.05)
      cerebrovascular reactivity to carbon dioxide. This reduction was greater during
      SNP-induced hypotension (P < 0.05). We conclude that cerebrovascular reactivity
      to carbon dioxide was attenuated during isoflurane and SNP-induced hypotension,
      and that it was better preserved during isoflurane-induced hypotension.

PMID- 7718376
TI  - Lack of bronchodilator effect after administration of subanaesthetic
      concentration of isoflurane in mild asthmatic subjects challenged with
      methacholine.
AB  - Volatile anaesthetics used in high concentrations are potent bronchodilators. The
      effect of lower subanaesthetic concentrations is less documented, particularly in
      humans with provoked bronchial obstruction. We have studied seven mild asthmatic
      subjects twice, 1 week apart, during an asymptomatic period. A provocative test
      with methacholine was performed to produce a decrease in forced expiratory volume
      in 1 s (FEV1) of at least 20%. The subjects then inhaled either 100% oxygen or
      0.75% isoflurane in oxygen for 8 min, via a face mask. During isoflurane
      inhalation, the subjects lost consciousness but recovered quickly. There was no
      significant improvement in FEV1 and maximum expiratory flow at 50% vital capacity
      (MEF50) recorded 3, 6, 9, 14 and 19 min after the end of isoflurane inhalation
      compared with time-control values. We conclude that lung function in mild
      asthmatic subjects challenged with methacholine was not improved after
      administration of a low subanaesthetic concentration of isoflurane. This may be
      important during recovery from general anaesthesia.

PMID- 7718378
TI  - Interactions between opioid drugs and propofol in laboratory models of seizures.
AB  - Propofol (i.v. and i.p.) exhibited anticonvulsant activity in three models of
      seizure in the mouse, induced by bicuculline, kainic acid and N-methyl-DL
      aspartic acid (NMDLA). Morphine, pethidine and fentanyl, which showed a biphasic
      dose-response relationship with respect to seizure modulation, abolished the
      anticonvulsant activity of propofol to exhibit their own intrinsic activity in
      proconvulsant doses. This occurred with very low doses of fentanyl and pethidine
      (15 micrograms kg-1 and 0.5 mg kg-1, respectively) in the NMDLA model. Thus it
      appears that propofol has anticonvulsant activity only when a convulsion is
      elicited directly; it does not prevent the actions of compounds that lower
      seizure threshold to convulsant stimuli. The anticonvulsant doses of morphine and
      fentanyl did not summate with the anticonvulsant activity of propofol. However,
      there was some evidence of summation of anticonvulsant activity between pethidine
      and propofol in the NMDLA model.

PMID- 7718377
TI  - Cutaneous heat loss in children during anaesthesia.
AB  - We have measured non-evaporative, cutaneous heat loss using heat flux transducers
      at eight skin sites in five children during anaesthesia and compared the data
      with basal metabolic heat production. The effect of disposable surgical covering
      and a radiant heater on heat flux was examined. The mean total heat flow rate
      before draping was 3-9 W higher than the basal metabolic rate after induction of
      anaesthesia with a simultaneous decrease in rectal temperature. Mean cutaneous
      heat loss was 62 (SD 9) W m-2 (9.5 (2.1) kJ kg-1 h-1) in children older than 1 yr
      and 84 W m-2 (17.2 kJ kg-1 h-1) in a 3-month-old infant. Disposable drapes
      diminished cutaneous heat loss by 29% and a radian heater by 77%. Heat conduction
      to the mattress was 21 (7) W m-2. These results showed that the decrease in core
      temperature after induction of anaesthesia was genuine cooling, that is heat loss
      exceeded heat production.

PMID- 7718379
TI  - Comparison of the effects of four i.v. anaesthetic agents on polymorphonuclear
      leucocyte function.
AB  - Initial resistance of bacterial infection is mediated primarily by
      polymorphonuclear leucocytes (PMN). Anaesthetic agents have been reported to
      impair various aspects of PMN function. It is possible that the use of these
      agents to sedate critically ill patients may further compromise an already
      depressed host defence mechanism. A flow cytometric technique with fresh whole
      blood from 10 healthy volunteers was used. Phagocytic and respiratory burst
      activity of PMN incubated for 1 h with either propofol, thiopentone, midazolam or
      ketamine at both clinical plasma concentrations and 100 times this concentration
      were determined. Thiopentone at the higher concentration reduced both respiratory
      burst activity (mean peak channel 50.7 compared with control value of 77.6 (P <
      0.0001)) and phagocytosis (mean peak channel 47.5 compared with 79.9 (P <
      0.0001)). Ketamine at 100 times the clinical plasma concentration also reduced
      respiratory burst and phagocytosis, but this failed to reach statistical
      significance (P = 0.10 and P = 0.053, respectively). No significant depression
      occurred in the other groups. The results suggest that these i.v. anaesthetic
      agents, at clinically relevant concentrations, have minimal effects on PMN
      phagocytosis and oxygen free radical production. At higher concentrations
      thiopentone and ketamine may affect phagocytic function and thiopentone may
      impair intracellular cytolysis.

PMID- 7718380
TI  - Animal toxins.

PMID- 7718381
TI  - Transient radicular irritation after spinal anaesthesia with hyperbaric 5%
      lignocaine.
AB  - We have studied prospectively 600 patients who had spinal anaesthesia for minor
      surgery, to evaluate the incidence of transient radicular irritation after the
      block. The anaesthetic agent (hyperbaric 5% lignocaine, hyperbaric 0.5%
      bupivacaine or plain 0.5% bupivacaine) was chosen according to the anticipated
      duration of surgery. We obtained information after operation from 537 patients
      (282 by telephone, 255 by letter). Ten percent of patients anaesthetized with
      hyperbaric 5% lignocaine (27 patients) had transient bilateral radiating pain in
      the lower extremities, buttocks, or both. Typically the pain started within 24 h
      after spinal anaesthesia, lasted less than 2 days and was described as mild.
      Lignocaine was the only variable that correlated with this pain. Two patients
      complained of symptoms after hyperbaric 0.5% bupivacaine but these were atypical
      compared with pain after lignocaine. None of the patients anaesthetized with
      plain bupivacaine had similar complaints. We conclude that the use of 5%
      hyperbaric lignocaine for spinal anaesthesia should be reconsidered.

PMID- 7718382
TI  - Comparison of the haemodynamic effects of mivacurium and atracurium during
      fentanyl anaesthesia.
AB  - We have measured the haemodynamic effects of mivacurium 0.15 and 0.2 mg kg-1, and
      atracurium 0.5 mg kg-1 administered over 10-15 s in patients undergoing coronary
      artery bypass surgery under fentanyl anaesthesia. There were no significant
      haemodynamic changes in the atracurium group, other than a transient decrease in
      pulmonary arterial wedge pressure. Changes in heart rate were small in all three
      groups. Mivacurium 0.15 mg kg-1 produced changes of only small magnitude (12%
      decrease in mean arterial pressure and 16% decrease in systemic vascular
      resistance index) however, mivacurium 0.2 mg kg-1 produced a 25% reduction in
      mean arterial pressure, a 14% increase in cardiac index and a 35% decrease in
      systemic vascular resistance index. Erythema developed in two, three and seven
      patients after atracurium, mivacurium 0.15 mg kg-1 and mivacurium 0.2 mg kg-1,
      respectively. One patient exhibited a 54% decrease in mean arterial pressure,
      generalized erythema and bronchospasm after mivacurium 0.2 mg kg-1. The
      haemodynamic changes with mivacurium suggested histamine release.

PMID- 7718383
TI  - Onset of neuromuscular block is the same if the ipsilateral or contralateral limb
      to the injection site is used for monitoring.
AB  - We studied 40 healthy adult patients undergoing elective surgery who were
      premedicated with flunitrazepam. Before induction of anaesthesia, one of the
      upper limbs was cannulated and an i.v. infusion of 0.9% saline commenced.
      Patients were given fentanyl and thiopentone for induction of anaesthesia and
      then 50% (20 patients) received atracurium 0.5 mg kg-1 and the other 50%
      vecuronium 0.1 mg kg-1. Neuromuscular block (maximum degree of depression of the
      elicited first twitch and the onset time of depression of twitch height to 50%,
      90% and 100% of control) and skin temperature (at the thenar eminence) were
      monitored in both the limb with the i.v. infusion and the non-cannulated upper
      limb. There was no difference in onset time and degree of neuromuscular block
      between the two upper limbs. Skin temperature was not significantly different
      between the two upper limbs. We conclude that each upper limb, irrespective of
      whether an i.v. infusion is in progress, may be used for monitoring onset of
      neuromuscular block.

PMID- 7718384
TI  - Clinical presentation of "silent" meningiomas after general anaesthesia.
AB  - We present two patients who became unrousable within 48h after general
      anaesthesia for non-neurosurgical operations; both were found to have frontal
      meningiomas. Analysis of these and previous reports suggest that several
      anaesthetic and perioperative factors probably combine to contribute to the
      accelerated presentation of these previously "silent" tumours, and we recommend
      that dexamethasone should be administered early in the course of unexplained
      neurological deterioration after operation.

PMID- 7718385
TI  - Serum nitrogen oxides during nitric oxide inhalation.
AB  - A patient with acute respiratory failure secondary to leptospirosis was treated
      with 40 and 90 volumes per million inhaled nitric oxide. His serum nitrogen oxide
      concentration (nitrates and nitrites combined) increased 13-fold. The mechanisms
      for the formation and elimination of nitrates are discussed.

PMID- 7718386
TI  - Intraoperative cardiac arrest after unrecognized dynamic hyperinflation.
AB  - We report a case of intraoperative dynamic hyperinflation ("gas trapping") which
      led to cardiac arrest, with electromechanical dissociation. The features of this
      poorly recognized phenomenon are described.

PMID- 7718387
TI  - Upper limb compartment syndromes: a complication of malignant hyperthermia in a
      patient with ill-defined myopathy.
AB  - We report a case of compartment syndrome complicating malignant hyperthermia (MH)
      in a 12-yr-old girl with a history of myopathy and multiple skeletal deformities;
      she underwent bilateral Achilles tendon surgery. Marked oedema of both forearms
      became evident in the immediate postoperative period and resolved after
      conservative treatment. Compartment syndrome is a rare complication of MH. Early
      recognition and therapy may prevent the onset of muscle ischaemia and distal
      neurovascular deficit. The need for urgent surgery and repeated anaesthesia in
      the early phase of recovery from an acute episode of MH may thus be reduced.

PMID- 7718388
TI  - Retrograde cannulation of the jugular vein: erroneous positioning of the catheter
      in the subarachnoid space.
AB  - This report describes one complication related to retrograde positioning of a
      catheter in the jugular vein in a patient in a coma resulting from subarachnoid
      haemorrhage. The catheter was found in the cervical subarachnoid space, as
      confirmed by radiography with contrast medium. Attention is focused on the fact
      that this technique, usually performed easily and safely, may occasionally
      present potentially severe complications.

PMID- 7718389
TI  - Airway management for tracheal tear.

PMID- 7718390
TI  - Rocuronium for caesarean section.

PMID- 7718391
TI  - Rocuronium for caesarean section.

PMID- 7718392
TI  - Rocuronium for caesarean section.

PMID- 7718393
TI  - Preoperative fasting for paediatric anaesthesia.

PMID- 7718394
TI  - Posterior column sensory impairment during ambulatory extradural analgesia in
      labour.

PMID- 7718395
TI  - Meningitis after combined spinal-extradural anaesthesia in obstetrics.

PMID- 7718396
TI  - Meningitis after combined spinal-extradural anaesthesia in obstetrics.

PMID- 7718397
TI  - Near-infrared spectroscopy in adults.

PMID- 7718398
TI  - Inhaled nitric oxide in acute respiratory failure.

PMID- 7718399
TI  - Postoperative extradural analgesia.

PMID- 7718400
TI  - Neuromuscular block and tourniquets.

PMID- 7718401
TI  - Spinal anaesthesia and aspirin.

PMID- 7718402
TI  - An emerging role for protein kinases: the response to nutritional and
      environmental stress.

PMID- 7718403
TI  - Ca(2+)-sensitive adenylyl cyclases.

PMID- 7718404
TI  - Peptides as probes for G protein signal transduction.
AB  - Triggered by agonist binding to cell surface receptors, the heterotrimeric G
      proteins dissociate into alpha and beta gamma subunits, each activating distinct
      second messenger pathways. Peptides from the primary sequences of receptors, G
      proteins, and effectors have been used to study the molecular interactions
      between these proteins. Receptor-derived peptides from the second, third and
      fourth intracellular loops and certain naturally occurring peptides antagonize G
      protein interactions and can directly activate G protein. These peptides bind to
      G protein sites that include the N and C terminal regions of the alpha subunit
      and a yet to be identified region of the beta subunit. Peptides have also been
      useful in characterizing G protein-effector interactions. The identification of
      the contact sites between proteins involved in G protein signal transduction
      should aid in the development of non-peptide mimetic therapeutics which could
      specifically modify G protein-mediated cellular responses.

PMID- 7718405
TI  - Molecular biology of the cyclic AMP-specific cyclic nucleotide
      phosphodiesterases: a diverse family of regulatory enzymes.

PMID- 7718407
TI  - Inhibitors of protein kinase C.

PMID- 7718406
TI  - Pharmacology and structure of high conductance calcium-activated potassium
      channels.

PMID- 7718408
TI  - Calcium uptake and gp80 messenger RNA destabilization follows cAMP receptor down
      regulation in Dictyostelium discoideum.
AB  - The mechanism by which high concentrations of cAMP selectively destabilize the
      gp80 mRNA in Dictyostelium discoideum was investigated. This treatment which
      leads to down-regulation of the cAMP receptor was also found to cause an increase
      in calcium uptake. Given this observation, we sought a role for calcium as a
      second messenger in the degradation of the gp80 mRNA. Changes in the mRNA levels
      were examined after treating cells with compounds known to alter their
      intracellular Ca2+ concentrations. This included the use of A23187, Ca2+, 8-(N,N
      diethylamino)octyl-3,4,5-trimethoxybenzoate HC1 (TMB-8), LiCl and 8-p
      chlorophenylthioadenosine 3',5'-cyclic monophosphate (ClPhS-Ado-3':5'-P). The sum
      of the data suggest that it is the cAMP-induced influx of Ca2+ across the plasma
      membrane, as apposed to a cAMP-mediated release of Ca2+ from intracellular
      stores, that initiates gp80 mRNA degradation. Treatment of cells with
      Concanavalin A (ConA) to induce cAMP receptor down-regulation, also causes a
      reduction in gp80 mRNA levels and an increase in calcium uptake.

PMID- 7718409
TI  - Insulin secretion and intracellular Ca2+ rises in monolayer cultures of neonatal
      rat beta-cells.
AB  - Glucose-induced insulin release, glucose-induced rises in intracellular free Ca2+
      concentration ([Ca2+]i), and voltage-dependent Ca2+ channel activity were
      assessed in monolayer cultures of beta-cells from 3-5-day-old rats. The glucose
      stimulated insulin secretory responses and [Ca2+]i rises were like those in adult
      rat beta-cells rather than fetal rat beta-cells. Voltage-dependent Ca2+ channel
      antagonists decreased glucose-induced insulin secretion, aborted the [Ca2+]i rise
      and, like deprivation of extracellular Ca2+, prevented the glucose-induced rise
      in [Ca2+]i when added before the glucose challenge. The presence of nifedipine
      sensitive, voltage-dependent Ca2+ channels was demonstrated directly by measuring
      Ca2+ currents using the whole-cell configuration of the patch-clamp technique and
      indirectly by measuring [Ca2+]i after membrane depolarization by 45 mM K+ or 200
      microM tolbutamide. Thus, in cultured beta-cells of 3-5-day-old rats the coupling
      of glucose stimulation to Ca2+ influx is essentially mature, in contrast to what
      has been reported for fetal or very early neonatal cells.

PMID- 7718410
TI  - Mechanisms of ATP-induced Ca2+ signaling in osteoclasts.
AB  - We investigate the mechanisms underlying the intracellular calcium pulse that
      occurs in response to extracellular adenosine triphosphate (ATP) in osteoclasts.
      We find that pre-loading of GDP-beta-S abolishes the response in Ca(2+)-free
      medium, demonstrating an internal release of Ca2+ via a pathway that involves a G
      protein. GDP-beta-S does not block in normal Ca(2+)-containing medium, suggesting
      that ATP also induces a Ca2+ influx across the cell membrane. We confirmed this
      using the Mn2+ quenching technique, which shows significant opening of Ca2+
      channels. We find a smaller response to adenosine diphosphate (ADP) and 2
      methylthio-ATP (2-MeSATP), but no response to beta, gamma-methylene-ATP (AMP
      PCP), adenosine monophosphate (AMP) or uridine triphosphate (UTP). Prior
      application of AMP and UTP, but not AMP-PCP, blocks the response to ATP. Our
      results indicate that the receptor is a P2 subtype that is not characteristic of
      any previously reported P2 receptor or combination of P2 receptors.

PMID- 7718411
TI  - Superoxide generation by guinea-pig peritoneal macrophages is inhibited by
      rolipram, staurosporine and mepacrine in an agonist-dependent manner.
AB  - Platelet-activated factor (PAF) (EC50 -7.9 +/- 0.6 M), formyl-methionyl-leucyl
      phenylalanine (fMPL) (EC50 -7.7 +/- 0.1M), phorbol 12-myristate 13 acetate (PMA)
      (EC50 -8.4 +/- 0.3 M), opsonized zymosan (OPZ) (0.01-1 mg/ml) were potent stimuli
      to superoxide generated by guinea-pig peritoneal macrophages. Superoxide
      generation by low (< or = -8M) concentrations but not high (> or = -7M)
      concentrations of PAF or fMLP were attenuated by rolipram (100 microM) in the
      presence of 1 microM prostaglandin E2 (PGE2). That stimulated by PMA or OPZ,
      however, was unaffected. At 1 microM, staurosporine was a potent inhibitor of
      superoxide generation stimulated by both fMLP and PAF but was without effect on
      that stimulated by OPZ. Superoxide generation stimulated by fMLP, PAF and OPZ was
      inhibited by 100 microM mepacrine. We conclude that superoxide generation
      stimulated by the chemoattractants fMLP and PAF involves a cyclic AMP regulated
      and cyclic AMP independent process. The cyclic AMP independent process is
      mediated by protein kinase C. Although protein kinase C seems a central element
      in the respiratory burst stimulated by fMLP, PAF and PMA that stimulated by OPZ
      bypasses this mechanism. Phospholipase A2 however, represents a common stage in
      the signal transduction pathway.

PMID- 7718412
TI  - Identification of type-2 phosphatidic acid phosphohydrolase (PAPH-2) in
      neutrophil plasma membranes.
AB  - Plasma membrane phosphatidic acid phosphohydrolase (PAPH) plays an important role
      in signal transduction by converting phosphatidic acid to diacylglycerol. PAPH-2,
      a Mg(2+)-independent, detergent-dependent enzyme involved in cellular signal
      transduction, is reportedly absent from the plasma membranes of neutrophilic
      leukocytes, a cell that responds to metabolic stimulation with abundant
      phospholipase D-dependent diacylglycerol generation. The present study was
      designed to resolve this discrepancy, focusing on the influence of cellular
      disruption techniques, detergent availability and cation sensitivity on the
      apparent distribution of PAPH in neutrophil subcellular fractions. The results
      clearly indicate the presence of two distinct types of PAPH within the
      particulate and cytosolic fractions of disrupted cells. Unlike the cytosolic
      enzyme, the particulate enzymes was not potentiated by magnesium and was strongly
      detergent-dependent. The soluble and particulate enzymes displayed dissimilar pH
      profiles. Separation of neutrophil particulate material into fractions rich in
      plasma membranes, specific granules and azurophilic granules by high speed
      discontinuous density gradient centrifugation revealed that the majority of the
      particulate activity was confined to plasma membranes. This activity was not
      inhibited by pretreatment with n-ethyl-maleimide in concentrations as high as 25
      mM. PAPH activity recovered in the cytosolic fraction of disrupted neutrophils
      was almost completely inhibited by 5.0 mM n-ethylmaleimide. We conclude that
      resting neutrophils possess n-ethylmaleimide-resistant PAPH (type 2) within their
      plasma membranes. This enzyme may markedly influence the kinetics of cell
      activation by metabolizing second messengers generated as a result of activation
      of plasma membrane phospholipase D.

PMID- 7718414
TI  - Activation of murine macrophages by hydrogen peroxide.
AB  - Hydrogen peroxide at concentrations from 0.1 to 20 microM enhances phagocytosis
      and oxidative burst of murine peritoneal macrophages. The activation of these
      macrophage functions is paralleled by prolonged hyperpolarization and a transient
      increase in cytoplasmic free calcium concentration. All the effects are dose- and
      time-dependent. The results obtained for H2O2 are compared with those for a
      natural activator, peptide N-formyl-methionyl-leucyl-phenylalanine. The data
      demonstrate the ability of small doses of hydrogen peroxide to stimulate
      macrophages through the intracellular mechanisms of ion transduction.

PMID- 7718413
TI  - The interaction of N-formyl peptide chemoattractant receptors with the membrane
      skeleton is energy-dependent.
AB  - Desensitization of N-formyl peptide chemoattractant receptors (FPR) in human
      neutrophils is thought to be achieved by lateral segregation of receptors and G
      proteins within the plane of the plasma membrane resulting in an interruption of
      the signalling cascade. Direct coupling of FPR to membrane skeletal actin appears
      to be the basis of this process; however, the molecular mechanism is unknown. In
      this study we investigated the effect of energy depletion on formation of FPR
      membrane skeleton complexes. In addition the effect of the protein kinase C
      inhibitor stauroporine and the phosphatase inhibitor okadaic acid on coupling of
      FPR to the membrane skeleton was studied. Human neutrophils were desensitized
      using the photoreactive agonist N-formyl-met-leu-phe-lys-N'-[125I]2(p
      azidosalicylamido)ethyl-1,3' - dithiopropionate (fMLFK-[125I]ASD) after ATP
      depletion with NaF or after incubation with the respective inhibitors. The
      interaction of FPR with the membrane skeleton was studied by sedimentation of the
      membrane skeleton-associated receptors in sucrose density gradients. Energy
      depletion of the cells markedly inhibited the formation of FPR-membrane skeleton
      complexes. This does not appear to be related to inhibition of protein
      phosphorylation due to ATP depletion because inhibition of protein kinases and
      phosphatases had no significant effect on coupling of FPR to the membrane
      skeleton. We conclude, therefore, that coupling of FPR to the membrane skeleton
      is an energy-dependent process which does not appear to require modification of
      the receptor protein by phosphorylation.

PMID- 7718415
TI  - Vasculitic syndromes.

PMID- 7718416
TI  - Systemic disorders with rheumatic manifestations.

PMID- 7718417
TI  - Immunodiagnostic and pathophysiologic aspects of antineutrophil cytoplasmic
      antibodies in vasculitis.
AB  - Antineutrophil cytoplasmic antibodies (ANCA) are a heterogeneous group of
      autoantibodies with a wide and diverse range of clinical associations. In
      vasculitis, the diagnostic utility of proteinase 3 (PR3)-ANCA and myeloperoxidase
      ANCA for Wegener's granulomatosis and microscopic polyangiitis, respectively, is
      now well established. Because of their significance as tools for diagnosis and
      prognosis, these autoantibodies have been analyzed extensively as markers for
      underlying immunopathogenic disturbances. In this review, we consider recent
      advances in the understanding of ANCA, focusing on their detection, diagnostic
      value, and role in the pathogenesis of vasculitis. In addition, promising new
      ways have been developed to elucidate the pathophysiologic and diagnostic
      relevance of the ANCA target antigens PR3 and myeloperoxidase. A great deal of
      attention and controversy has focused on the possible mechanisms underlying the
      ANCA-related immune response, such as antigenic cross-reactivity between human
      polymorphonuclear leukocyte proteins and extrinsic antigens by molecular mimicry,
      idiotype network regulation, and T cell reactivity to PR3 and myeloperoxidase.

PMID- 7718418
TI  - Distinguishing polyarteritis nodosa from microscopic polyangiitis and
      implications for treatment.
AB  - The vasculitides are a heterogeneous group of disorders for which classification
      is needed to facilitate diagnosis and treatment. Recent studies based on a more
      comprehensive clinical analysis of symptoms and virologic investigations favor
      the recognition, in the polyarteritis nodosa (PAN) group, of a distinct form of
      systemic vasculitis called microscopic polyangiitis (MPA). This distinction may
      be confusing, so the features of each condition need to be more precisely
      defined. Differentiation between PAN and MPA cannot be based on only histologic
      criteria. Clinical manifestations (especially lung and kidney involvement),
      biologic signs (antineutrophil cytoplasmic antibodies and hepatitis B and C
      infection), and angiographic data must be taken into consideration. Therapeutic
      strategy should differ dramatically, depending on whether primary or secondary
      MPA or PAN has been diagnosed, and treatment optimization is certainly the best
      reason for improving the classification of the systemic vasculitides.

PMID- 7718419
TI  - Molecular approaches toward pathologic mechanisms in giant cell arteritis and
      Takayasu's arteritis.
AB  - Molecular techniques have provided new tools to define genetic systems involved
      in disease susceptibility and to dissect molecular events driving inflammatory
      reactions. Inflammatory infiltrates in the wall of large and medium-sized
      arteries, sometimes associated with giant cell formation, are pathognomic for
      Takayasu's arteritis (TA) and giant cell (cranial) arteritis. Molecular
      techniques have been used successfully to define genetic host factors involved in
      disease susceptibility and to dissect the nature of inflammatory cells and
      mediators in the pathologic lesions. Careful analysis of incidence data for TA
      suggests that TA is a worldwide disease. Genetic comparison of western and
      eastern TA, however, raises the possibility of disease heterogeneity. Emerging
      data indicate that HLA-DRB1 genes represent important risk factors in giant cell
      arteritis. Whether disease association is related to the role of HLA-DR molecules
      in presenting a disease-inducing antigen remains to be seen. Analysis of the
      molecular diversity of tissue-infiltrating T cells indicates that a small
      proportion of CD4+ T cells proliferate in situ, potentially as a result of
      antigen recognition. Tissue cytokine profiles reveal functional selection of T
      cells and are compatible with the model that Th1 cells recognize antigen on the
      surface of activated macrophages. The presence of T cell-derived cytokines in
      temporal artery tissue of patients with polymyalgia rheumatica who are lacking
      microscopic inflammation indicates subclinical vasculitis.

PMID- 7718420
TI  - Evaluation and treatment of central nervous system vasculitis.
AB  - Angiitis of the central nervous system (CNS) remains a poorly understood and
      clinically challenging form of vascular inflammatory disease. Primary angiitis of
      the CNS (PACNS) has been viewed as a relentless and uniformly fatal disorder if
      untreated. In addition, recent trends have demonstrated an increasing reliance on
      angiographic diagnosis without tissue confirmation. It has been suggested that
      PACNS is clinically more heterogeneous than previously appreciated and may
      include relatively benign subsets. A reappraisal of diagnostic approaches has
      suggested caution in the diagnosis of CNS angiitis on purely angiographic
      grounds. Secondary vasculitis of the CNS is even more heterogeneous. Clinicians
      involved in the evaluation of patients with presumed CNS vasculitis need to be
      aware of the clinical spectrum of vascular inflammatory disease within the CNS as
      well as the strengths and limitations of currently available diagnostic
      modalities.

PMID- 7718421
TI  - Adhesion molecules, sex steroids, and the pathogenesis of vasculitis syndromes.
AB  - The pathogenesis of the vasculitis syndromes slowly continues to yield its
      secrets. Over the past year, evidence has continued to accumulate, indicating
      that the endothelium exhibits a wide range of regulatory functions, mediated in
      large part through adhesion molecules. Several studies showed increased
      expression of such molecules in vasculitis. New appreciation of the Shwartzman
      reaction, which could explain non-immune complex-mediated vascular inflammation,
      continues to mount and to point toward potential future therapies. Soluble
      adhesion molecules were studied as potential diagnostic tools and/or markers of
      disease activity. Anti-endothelial cell antibodies (AECA) remain controversial as
      potential mediators of vasculitis. The results of recent studies suggest that
      AECA may be seen more frequently in ANCA-negative vasculitis and that AECA
      possess unique antigenic specificities in Wegener's granulomatosis and systemic
      lupus erythematosus. Sex steroids were shown to affect the expression of
      endothelial adhesion molecules, in addition to possessing well documented
      immunoregulatory properties. These findings may point to a critical role for sex
      steroids in the pathogenesis of vasculitis syndromes with female predominance,
      particularly Takayasu's arteritis.

PMID- 7718422
TI  - Systemic disorders with rheumatic manifestations.

PMID- 7718423
TI  - Musculoskeletal syndromes associated with malignancies.
AB  - Literature on the association of malignancies with various rheumatic disorders
      published over the past year is summarized in this review. The possible roles of
      methotrexate treatment in predisposing to the development of lung cancer and
      Felty's syndrome in predisposing to non-Hodgkin's lymphoma in rheumatoid
      arthritis patients are discussed. The increased occurrence of monoclonal
      gammopathies and non-Hodgkin's lymphoma in patients with Sjogren's syndrome is
      reported. The possible increased frequency of malignancies among patients with
      systemic lupus erythematosus (SLE), scleroderma, and polymositis-dermatomyositis
      is revisited; of interest, the overlapping clinical features of non-Hodgkin's
      lymphoma and SLE are presented, as well as the increased occurrence of ovarian
      cancer in patients (especially older women) with dermatomyositis. The proceedings
      of the first International Workshop on Hypertrophic Osteoarthropathy, as well as
      the association of this syndrome with nasopharyngeal carcinoma in the childhood
      years, are presented. Finally, postchemotherapy and post-bacille Calmette-Guerin
      rheumatism are described.

PMID- 7718424
TI  - Rheumatic manifestations of disorders of the central and peripheral nervous
      system.
AB  - Many inflammatory rheumatic conditions may result, in part, from local release of
      sensory neuropeptides; substance P is currently the best studied of these.
      Various neurologic diseases that result in movement disorders continue to come to
      the attention of rheumatologists, primarily because of the pain and stiffness
      associated with them, and they are often misdiagnosed. Neuroarthropathies remain
      the most distinctive of the joint disorders that appear to result directly from
      neurologic injury, but little new information concerning these disorders has been
      generated in the past year.

PMID- 7718425
TI  - Cryoglobulinemia and other dysproteinemias, familial Mediterranean fever, and
      POEMS syndrome.
AB  - The introduction of newer technology in the past few years, especially the use of
      second-generation enzyme-linked immunosorbent assays, recombinant immunoblot
      assays, reverse transcriptase, and DNA amplification, have clearly defined the
      role of hepatitis C virus as the most important etiologic factor in the
      development of mixed cryoglobulinemia. This has led to a better understanding of
      the pathogenic mechanisms involved in disease expression, particularly
      vasculitis, and also has provided a rationale for the use of interferon alfa and
      other antiviral drugs in the therapy of these disorders. The clinical
      manifestations of the syndrome also have been well characterized, as well as some
      of the risk factors. There also has been an improvement in our understanding of
      the pathogenic mechanisms involved in multiple myeloma and related monoclonal
      gammopathies, as well as several attempts to improve early recognition of bone
      disease with magnetic resonance imaging. The susceptibility gene for familial
      Mediterranean fever has been better characterized, as have risk factors for
      colchicine toxicity. The role of cytokines has been better delineated for both
      monoclonal gammopathies and POEMS (polyneuropathy, organomegaly, endocrinopathy,
      M protein, and skin changes) syndrome.

PMID- 7718426
TI  - Immunodeficiency states and associated rheumatic manifestations.
AB  - For immunodeficiency states, the past year has been marked with the discovery of
      a series of events at the gene level and cell-to-cell interaction, particularly
      in common variable immunodeficiency, severe combined immunodeficiency, IgA
      deficiency, and immunodeficiency associated with IgM hyperimmunoglobulinemia.
      Clinical expression, especially in the musculoskeletal system, as well as
      infectious complications and therapy, also have been reported.

PMID- 7718427
TI  - Hematologic disorders including sickle-cell syndromes, hemophilia, and beta
      thalassemia.
AB  - A review of the literature on rheumatologic manifestations in hematologic disease
      supports the idea that magnetic resonance imaging is useful in the identification
      of tissue patterns suggestive of vasoocclusion and myonecrosis in sickle-cell
      anemia and in diagnosing significant synovial hypertrophy in hemophilia. With
      reference to treatment, the use of yttrium-90 silicate and P-32 colloid for
      radiosynovectomy in patients with hemophilic arthropathy and the latest results
      of total joint replacement surgery in sickle-cell anemia and hemophilia patients
      are discussed.

PMID- 7718428
TI  - Hyperlipidemia, amyloidosis, sarcoidosis, iron storage disease, and Wilson's
      disease.
AB  - The objective of this review is to summarize the most recent developments related
      to this miscellaneous group of diseases. Emphasis has been placed on information
      that will help the practicing physician, such as clinical observations, improved
      diagnostic techniques, particularly ones that are noninvasive or minor, and new
      therapeutic approaches. An interesting animal study that helps in the
      understanding of the increased frequency of coronary artery disease in patients
      with long-standing systemic lupus erythematosus is described.

PMID- 7718429
TI  - Evaluation of liquid chromatography coupled with high-field 1H NMR spectroscopy
      for drug metabolite detection and characterization: the identification of
      paracetamol metabolites in urine and bile.
AB  - The applicability of coupled reversed-phase high performance liquid
      chromatography (HPLC)-NMR spectroscopy for the detection and identification of
      paracetamol (N-(4-hydroxyphenyl)acetamide) and its sulfate, glucuronide and N
      acetylcysteinyl metabolites in the unprocessed biological fluids, human urine,
      rat urine and rat bile, is investigated. Analysis of these samples was performed
      by gradient HPLC elution and directly coupled 500 MHz 1H NMR spectroscopy
      detection using a combination of one- and two-dimensional NMR methods in stopped
      flow mode. The stopped-flow approach is demonstrated to be an efficient technique
      for identification of drug metabolites which have, for example, a UV-chromophore.
      Stopped-flow HPLC analysis with NMR detection is a viable technique and halting
      the chromatographic process several times during a run has a negligible effect on
      the separation and NMR characterization. The post-acquisition data processing
      method of 'quantified maximum entropy' is shown to provide a means of improving
      the quality of spectra for minor components, thus aiding NMR resonance
      assignments.

PMID- 7718430
TI  - Health and infarcted brain tissues studied at short diffusion times: the origins
      of apparent restriction and the reduction in apparent diffusion coefficient.
AB  - The significance of NMR water diffusion measurements performed at short diffusion
      times (< 10 ms) for brain tissue is examined. An apparent restriction to
      diffusion for both healthy and cytotoxically edematous tissue is shown: cytotoxic
      edema lengthens the diffusion time at which this phenomenon is visible. The
      dramatic reduction in apparent diffusion coefficient (ADC) observed in the core
      of cytotoxic edema is explained in terms of the enclosure of extracellular water
      in non-contiguous pockets in conjunction with the shift of water from the extra
      to the intracellular space. The model presented provides an explanation for the
      ADC reduction without recourse to changes in the cell membrane permeability to
      water, or unrealistic values for the extra- and intracellular diffusion
      coefficients.

PMID- 7718431
TI  - Absolute quantitative proton NMR spectroscopy based on the amplitude of the local
      water suppression pulse. Quantification of brain water and metabolites.
AB  - Quantification in localized proton NMR spectroscopy has been achieved by various
      methods in recent years. A new method for absolute quantification is described in
      this paper. The method simultaneously rules out problems with B1 field
      inhomogeneity and coil loading, utilizing a relation between the locally
      optimized amplitude of a chemical shift selective water suppression pulse and the
      acquired signal. Validity and feasibility of quantification using the method of
      the water suppression pulse is demonstrated. Brain water and cerebral metabolites
      have been quantified in a study of 12 healthy volunteers. Localized proton NMR
      spectra were obtained from a region of primarily white matter in the occipital
      lobe. The observable water content in the NMR spectra was 0.685 +/- 0.025. The
      absolute metabolite concentrations were: [total choline] = 1.25 +/- 0.21 nM,
      [total creatine] = 6.71 +/- 0.59 nM and [NAA] = 9.15 +/- 0.74 nM. It is concluded
      that the quantification method is easily applied in vivo, and that the absolute
      concentrations obtained are similar to results in other studies except those
      relying on assumptions of the concentration of an internal reference. The
      advantage of the quantification method reported here is that it is independent of
      the assumptions needed for other methods.

PMID- 7718432
TI  - Effects of high energy shock waves on tumor blood flow and metabolism: 31P/1H/2H
      nuclear magnetic resonance study.
AB  - The effects of high energy shock waves (HESW) on tumor cell metabolism and tumor
      blood flow were studied in the NU-1 kidney cancer xenograft by multinuclear
      1H/2H/31P magnetic resonance spectroscopy. Tumor xenografts were exposed to 800
      HESW using an experimental electromagnetic shock wave emitter based on the
      Siemens Lithostar Plus, which is used for clinical lithotripsy. Exposure of
      tumors to 800 HESW resulted in a temporary decrease of tumor blood flow (TBF)
      determined by the 2H NMR monitoring of the 2HO1H wash-out after intratumoral
      injection. By concomitant recording of 31P and 1H NMR spectra, tumor pH, high
      energy phosphates and lactate levels were followed. Tumor treatment with HESW
      transiently resulted in acidification, ATP decrease, P(i) increase and lactate
      increase. In contrast, HESW administration adjacent to the tumor did not
      significantly influence TBF, tumor pH, high-energy phosphates or lactate levels,
      showing that the observed alterations are caused by an interaction of HESW and
      tumor tissue. The most likely explanation for these observations is that HESW
      administration causes local vascular malfunctioning followed by a reduction in
      oxygen and nutrient supply to the tumor which leads to a decreased aerobic energy
      metabolism. The results of this study may be used to aid the design of HESW-based
      therapies.

PMID- 7718433
TI  - Dysfunctional activation of subcortical nuclei in palatal myoclonus detected by
      high-resolution MRI.
AB  - Magnetic resonance images that were sensitized to changes in cerebral blood
      oxygenation state demonstrated dysfunctional activation of the dentate nuclei,
      the left inferior olivary nucleus and the left red nucleus in a 56-year-old
      patient with palatal myoclonus. These findings represent the first demonstration
      of movement-related activation of cerebellar, brainstem and midbrain nuclei in a
      single subject and at a spatial resolution comparable to that of anatomic MR
      images.

PMID- 7718434
TI  - 19F NMR magnetization transfer between 5-FBAPTA and its complexes. An alternative
      means for measuring free Ca2+ concentration, and detection of complexes with
      protein in erythrocytes.
AB  - The 19F NMR Ca(2+)-indicator molecule 5,5'-difluoro-1,2-bis(o-
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (5-FBAPTA) was used in a procedure
      that enhances its range of applications to measuring free Ca2+ concentrations in
      buffer solutions and human erythrocytes. Even if the signal from the Ca-5-FBAPTA
      complex was not visible, the concentration of the complex could be calculated
      from saturation transfer spectra. This was demonstrated with well characterized
      buffer solutions in vitro and shown to also apply to concentrated haemolysates.
      The analysis required a precise estimate of the dissociation rate constant of the
      complex; this was found to be 295/s at 37 degrees C and the corresponding
      association rate constant was 4.1 x 10(8) L/mol/s. These values differ from those
      obtained previously in different buffer conditions and by two different NMR
      methods. A series of spectra were acquired from haemolysates containing 5-FBAPTA,
      in which saturating irradiation was applied at a frequency that was progressively
      off-set from the carrier frequency. Saturation transfer to the free 5-FBAPTA was
      seen from irradiation at frequencies different from that of Ca-5-FBAPTA, thus
      suggesting the presence of complexes with proteins.

PMID- 7718435
TI  - The breast implant controversy: psychosocial implications.

PMID- 7718436
TI  - Monica Morrow on the pros and cons of stereotactic breast biopsy.

PMID- 7718437
TI  - Physicians urged to find ways to determine patients' preferences about cancer
      treatment.

PMID- 7718438
TI  - Diagnostic and management issues in gallbladder carcinoma.
AB  - Carcinoma of the gallbladder is a rare malignancy, with an incidence rate in the
      United States of 2.2 to 4.4 per 100,000 persons. Its clinical presentation is
      nonspecific, and the majority of patients have advanced disease at presentation.
      The diagnosis is rarely made preoperatively. About 90% of gallbladder cancers are
      adenocarcinomas. Surgical treatment is curative for lesions localized to the
      mucosa and submucosa, but these represent only about 16% of all gallbladder
      carcinomas. The role of radical surgery with node dissection and liver resection
      is controversial. Chemotherapy and radiation therapy do not have a major role in
      the treatment of gallbladder carcinoma. The prognosis is very poor, with a 5-year
      survival rate of less than 5%.

PMID- 7718439
TI  - Amifostine shortens bone marrow recovery period in breast cancer patients.

PMID- 7718440
TI  - Percutaneous endoscopic stomas for enteral feeding and drainage.
AB  - The use of safe and cost-effective endoscopic techniques for the placement of
      tubes in the gastrointestinal tract has led to increased utilization of long-term
      enteral feeding in patients with impaired GI function, including many cancer
      patients. Of an estimated 148,000 US patients who received long-term enteral
      feeding outside hospitals in 1992, 43% were cancer patients. The technique of
      percutaneous endoscopic gastrostomy is used primarily for enteral feeding, but
      can also be used to place wide tubes for drainage of an obstructed GI tract.
      Aspiration problems can be eliminated by endoscopic placement of a feeding tube
      directly into the jejunum (percutaneous endoscopic jejunostomy). Patients with
      advanced cancer who are not surgical candidates may benefit from an external GI
      bypass placed endoscopically, which allows drainage through a gastrostomy and
      feeding through a jejunostomy distal to the obstruction.

PMID- 7718441
TI  - Clinical trials referral resource. Prostate cancer II.

PMID- 7718442
TI  - Current management of primary central nervous system lymphoma.
AB  - Primary CNS lymphoma is rising in incidence in both the AIDS and non-AIDS
      populations. It is a non-Hodgkin's lymphoma that usually presents as a brain
      tumor, but the leptomeninges, eyes, and spinal cord also are frequently affected.
      Systemic lymphoma is not present, and comprehensive systemic staging is
      unnecessary, but appropriate neurologic staging is imperative. Standard therapy
      has been whole brain radiotherapy, giving a median survival of 12 to 18 months in
      non-AIDS patients, but only 2 to 5 months in AIDS patients. In non-AIDS patients,
      the addition of chemotherapy to radiotherapy has improved the prognosis, with
      median survivals of 30 to 45 months. Current protocols focus on the development
      of combination chemotherapy programs and reducing the dose of cranial
      radiotherapy to minimize late neurologic sequelae. The addition of chemotherapy
      to brain irradiation prolongs survival in some patients with AIDS-related
      disease, but median survival is not significantly improved.

PMID- 7718443
TI  - Current management of meningiomas.
AB  - Although generally benign tumors, meningiomas can cause serious neurological
      injury and, at times, vexatious management difficulties. Currently, the accepted
      management of these tumors is attempted total surgical excision when technically
      possible and associated with an acceptable risk. However, even with innovations
      in instrumentation and refinements in surgical technique, the goal of total
      resection may not be achievable. For these patients, and for those with recurrent
      tumors, options for treatment include reoperation, radiation therapy, and
      chemotherapy. Recent developments in surgical technique and instrumentation,
      radiosurgery, and brachytherapy have increased the treatment options, while
      clinical trials with tamoxifen and mifepristone (RU486) are adding information on
      the effectiveness of these drugs as chemotherapeutic agents. While the search
      continues for a uniformly successful management plan, physicians must be aware of
      the available options and try to help the patient decide which treatment is
      appropriate, based on current medical knowledge.

PMID- 7718445
TI  - Tuberculosis.

PMID- 7718444
TI  - Yellow fever in 1992 and 1993.

PMID- 7718446
TI  - Dracunculiasis.

PMID- 7718447
TI  - Problem wounds: a nursing challenge (continuing education credit).

PMID- 7718448
TI  - Computer screening for early detection of melanoma--is there a future?
AB  - Computer image analysis in the study of pigmented lesions is critically examined
      and discussed in the light of the current published data. The potential for
      objective analysis by computers as a possible screening aid for the inexperienced
      clinician is discussed. The future for this technology is exciting if handled
      with care.

PMID- 7718449
TI  - Nail changes in epidermolysis bullosa: clinical and pathogenetic considerations.
AB  - Nail changes in epidermolysis bullosa (EB) are common, but although they are
      highly suggestive of the disease, they are not pathognomonic. They are the result
      of abnormalities of the nail matrix and nail bed, associated with the
      pathogenetic alterations of the dermo-epidermal junction which occur in EB. In
      addition, secondary trauma in the areas of epidermal-dermal separation, and
      chronic inflammation of the nail matrix, are probable contributory factors, even
      in non-scarring forms of EB. Recent developments in the molecular and cell
      biology of the cutaneous basement membrane zone have greatly advanced our
      understanding of the pathomechanisms underlying different subtypes of EB. Defects
      in genes coding for the structural proteins of the basement membrane zone have
      been defined in some EB subtypes, and abnormal expression of structural proteins
      in others. The data accumulated from study of these genetic disorders will
      contribute to knowledge of the role of the dermo-epidermal junction in the normal
      physiology and differentiation of the nails, and be of value in discerning the
      aetiopathogenesis of acquired nail diseases.

PMID- 7718450
TI  - p53 immunoreactivity is uncommon in primary cutaneous lymphoma.
AB  - p53 gene mutation appears to play an important role in the development of
      systemic lymphoma, and may be associated with tumour progression. Its role in
      cutaneous lymphoma is currently unknown. We examined p53 expression in 55
      biopsies of cutaneous lymphoma, including patch-, plaque- and tumour-stage
      mycosis fungoides (MF), T- and B-cell lymphoma and lymphomatoid papulosis.
      Strong, homogeneous p53 expression, thought to correlate most closely with p53
      gene mutation, was seen in only three cases; in a plaque and tumour from a
      patient with tumour-stage MF, in plaque-stage MF in a patient without tumours,
      and in one case of CD30+ large-cell anaplastic lymphoma. These data suggest that
      p53 gene mutation is not a critical step in the development of the majority of
      primary cutaneous lymphomas.

PMID- 7718451
TI  - Use of in situ detection of histone mRNA in the assessment of epidermal
      proliferation: comparison with the Ki67 antigen and BrdU incorporation.
AB  - The labelling index is commonly used as a measure of proliferation. However, the
      use of tritiated thymidine or BrdU labelling of S-phase cells is limited to
      prospective samples. We have employed an oligonucleotide cocktail complementary
      to the mRNA species encoding the replication-dependent histones H2B, H3 and H4
      for non-isotopic in situ hybridization (NISH), and have compared the resultant
      proliferation indices in normal skin with those obtained by bromodeoxyuridine
      (BrdU) incorporation and by Ki67 immunohistochemistry (IHC) using the monoclonal
      antibody MIB1. In addition, we compared the staining characteristics of histone
      NISH and Ki67 IHC in a further 25 samples from a variety of inflammatory
      dermatoses and neoplastic conditions, as well as from normal skin. In normal
      skin, S-phase (histone NISH and BrdU) and cycling (Ki67) cells were confined to
      the basal and low suprabasal layers. The labelling indices determined by histone
      NISH and BrdU incorporation were similar, whereas that of Ki67 IHC was four times
      greater. In biopsies from hyperproliferative dermatoses and dysplastic or
      malignant lesions, the number of histone NISH- and Ki67 IHC-positive cells was
      generally elevated; in accordance with the differential expression of these two
      markers during the cell cycle, MIB1 consistently gave higher results. The
      advantage of histone NISH over Ki67 IHC is that it is a marker of the same part
      of the cell cycle as BrdU incorporation. However, the combined use of both
      histone NISH and Ki67 IHC to measure two cell cycle parameters, namely S-phase
      and the number of cycling cells, allows more detailed retrospective study of
      epidermal proliferation than has been possible previously.

PMID- 7718452
TI  - Novel cycle changes in scalp hair are caused by etretinate therapy.
AB  - The scalp hair of 15 patients, who were treated with etretinate for at least 6
      months, was investigated, with the aims of confirming the previously described
      reduction in the duration of anagen and establishing the mechanism of etretinate
      alopecia. An increase in hair shedding rate and an increase in plucked telogen
      count, both of which continued for 6 months of treatment, were found, whereas
      there was no significant increase in the proportion of new, or regrowing, anagen
      hairs in a cut sample (NAH). The sustained decrease in the duration of anagen was
      confirmed, and it was further shown that this decrease was progressive. This
      would appear to be the main cause of the observed increased shedding associated
      with etretinate treatment. In relation to the mechanism of the alopecia, it was
      concluded that an arrest at the onset of anagen and a follicular anchorage defect
      in telogen were causes. The evidence for an arrest at the onset of anagen was a
      failure of NAH to rise on treatment, and a large increase in NAH on stopping
      treatment. The evidence for a follicular anchorage defect was a rise in shed rate
      very early in treatment, and an observed shed rate greater than expected, on the
      basis of plucked telogen results, later in treatment. These pathogenic mechanisms
      have never been described previously in drug-induced alopecia, or in the majority
      of hair disorders in general. However, it would seem highly unlikely that these
      mechanisms are exclusive to etretinate therapy.

PMID- 7718453
TI  - Regeneration pattern of blood vessels and nerves in cultured keratinocyte grafts
      assessed by confocal laser scanning microscopy.
AB  - The aim of this study was to investigate the pattern of both neovascularization
      and reinnervation, and the relationship between the two processes, in
      keratodermal grafts, using confocal laser scanning microscopy, at different time
      points during the healing process. Keratodermal grafts were prepared in pigs by
      combining autologous dermis with cultured autologous keratinocytes.
      Immunohistochemistry was carried out on thick cryostat sections (100-150
      microns), using antisera to the endothelial marker von Willebrand factor (vWf)
      and the pan-neuronal marker protein gene product 9.5 (PGP9.5). The results
      suggest that the neovascularization and reinnervation in the cultured
      keratodermal graft is almost complete at 6 weeks. Neovascularization precedes
      innervation, reaching the surface covered by the keratinocytes at 2 weeks,
      initially with a linear vascular pattern. From 3 weeks, there is a gradual
      arborization of the vessels to form a typical vascular plexus. The process of
      reinnervation is similar in pattern to that of neovascularization, although
      slower in developing a full network of fibres. In conclusion, the use of confocal
      microscopy allows the precise definition of complex patterns of
      neovascularization and nerve growth, which are not fully apparent when using
      conventional microscopy. Because angiogenesis occurs first, it probably plays a
      leading role in the survival of keratodermal grafts during wound healing. Indeed,
      new blood vessels form a pathway for the subsequent innervation process, and
      quickly reach the epidermal layer which, in turn, may play a key role in the
      tropism of both blood vessels and nerves.

PMID- 7718454
TI  - Decreased monocyte interleukin-1 beta production in atopic eczema.
AB  - It has been suggested that in atopic eczema (AE) a reduced lymphocyte response to
      T-cell mitogens in vitro is secondary to altered production of cytokines or
      inflammatory mediators. We investigated, in parallel, the mitogen-induced T-cell
      proliferation, monocyte interleukin-1 beta (IL-1 beta) production, and
      prostaglandin E2 (PGE2) production of monocytes and of peripheral blood
      mononuclear cells (PBMC) in AE patients and non-atopic controls. After
      stimulation with concanavalin A (Con A) PBMC of AE patients showed a
      significantly reduced proliferative response compared with the controls. The
      monocyte production of IL-1 beta after stimulation with lipopolysaccharide (LPS)
      was significantly decreased in AE. No differences between AE patients and
      controls were observed with regard to the PGE2 production of PBMC after
      stimulation with Con A or the monocyte release of PGE2 after LPS stimulation.
      Because IL-1 plays a central role in the activation of T-cell proliferation, the
      decreased monocyte IL-1 beta production may provide a plausible explanation for
      the reduced mitogen response of T cells in AE.

PMID- 7718455
TI  - Cutaneous barrier function after cold exposure in hairless mice: a model to
      demonstrate how cold interferes with barrier homeostasis among workers in the
      fish-processing industry.
AB  - Dry skin and eczema only seldomly occur in workers in the Danish fish-processing
      industry (FPI) during work, when their fingers and palms have a low skin surface
      temperature, low transepidermal water loss (TEWL), and a high capacitance.
      However, shortly after work, when the skin temperature has become normal, TEWL
      levels increase to above normal, and capacitance decreases to below normal,
      followed by the development of dry skin or chapping, which subsequently revert to
      normal over a period of hours. These observations suggest that workers in the FPI
      may have a defect in skin barrier function, which is, however, masked by a low
      skin temperature, resulting in misleadingly low TEWL levels during work. To test
      this hypothesis, we disrupted the permeability barrier in hairless mice with
      topical acetone, and exposed the treated skin to ice for 3.5 h. Although TEWL
      rates immediately after cold exposure were low, suggesting normal barrier
      recovery, TEWL increased to levels slightly above pre-cold exposure levels (i.e.
      levels just after the barrier was disrupted with acetone) when the skin
      temperature reverted to normal (> or = 15 min). The changes in TEWL were
      paralleled by equivalent changes in percutaneous penetration of the electron
      dense tracer lanthanum nitrate. This indicates that cold masks a defective
      barrier, and inhibits barrier repair. After a few hours at ambient temperatures,
      normal barrier recovery was observed. Electron microscopy revealed empty or
      partially empty lamellar bodies during the first 30 min post-cold exposure. After
      1 h the majority of nascent LBs displayed normal morphology. Moreover,
      histochemical studies showed a delayed reappearance of stratum corneum
      intercellular lipids following cold exposure. These results demonstrate that cold
      exposure prevents barrier recovery after acetone disruption, and provide an
      explanation for the occupational dermatosis observed in the fish-processing
      industry and related occupations.

PMID- 7718456
TI  - Normal sweat secretion rate in patients with alopecia areata.
AB  - We have examined sweat secretion rates in 22 patients with alopecia areata, and
      22 age- and sex-matched controls. Mean sweat rate on the forearm in patients with
      alopecia areata was 20 mg/cm2 per h (95% confidence limits 15-25 mg/cm2 per h),
      and in controls was 24.1 mg/cm2 per h (95% confidence limits 19.1-29.1 mg/cm2 per
      h). Sweat secretion was higher in males than females in both the disease and
      control groups (27.8 mg/cm2 per h [95% confidence limits 21.3-34.3 mg/cm2 per h],
      compared with 18.08 mg/cm2 per h [95% confidence limits 14.63-21.6 mg/cm2]; P >
      0.01). Our results confirm the previously reported sex difference in sweat
      secretion rate, and demonstrate that there is no statistically significant
      difference between patients with alopecia areata and controls. We discuss our
      results in the light of a previous report claiming that patients with alopecia
      areata have reduced rates of cholinergic-induced sweating.

PMID- 7718457
TI  - Cancer Research Campaign health education programme to promote the early
      detection of cutaneous malignant melanoma. I. Work-load and referral patterns.
AB  - From 1987 to 1989 a campaign to promote the early detection of cutaneous
      malignant melanoma was conducted in the areas of seven health authorities in
      England and Scotland (total population 3.6 million). Data were collected on
      17,155 patients attending pigmented lesion clinics (PLCs) in each study area
      during the campaign. After a dramatic rise in PLC referral rates in the first
      month of the campaign the average monthly referral rate among the target
      population in the study period settled to an average of 13 per 10(5), a twofold
      increase compared with the pre-campaign period. Over 85% of patients at all PLCs
      were seen within 4 weeks of referral from their general practitioners. The
      melanoma to non-melanoma detection ratio was (1:33). The organization of future
      early detection initiatives needs careful review and planning, in order to
      improve their effectiveness in all sections of the population, and to enable
      health services to cope with the increased work-load.

PMID- 7718458
TI  - Cancer Research Campaign health education programme to promote the early
      detection of cutaneous malignant melanoma. II. Characteristics and incidence of
      melanoma.
AB  - The effect on the detection and characteristics of melanoma, resulting from the
      Cancer Research Campaign's health education programme to promote the early
      detection of melanoma in the general population, was studied from 1987 to 1989.
      The seven study areas in England and Scotland yield a target population of 3.6
      million. Data were collected from local clinic-based registers, pathology
      laboratories, and the cancer registries. The average annual incidence rates of
      melanoma were seven and 12 per 10(5) in males and females, respectively, age
      standardized to England and Wales, 1988. These rates are similar to the national
      figures for Scotland, where there is a national melanoma register, but higher
      than those reported by the English and Welsh cancer registries. The incidence was
      significantly higher in females than males (P < 0.001), and increased with age.
      Fifty-three per cent and 65% of cases in males and females, respectively, were
      thin (Breslow thickness < or = 1.5 mm), similar to the national figures from
      Scotland. No significant decrease in the incidence of late-stage tumours was
      found in either sex as a result of the campaign. Because of difficulties with
      ascertainment of cases in England, the main evaluation will focus on future
      trends in mortality rates for melanoma.

PMID- 7718459
TI  - The effect of aspirin on haemostatic activity in the treatment of chronic venous
      leg ulceration.
AB  - An increased rate of venous ulcer healing with the use of oral enteric-coated
      aspirin (300 mg) daily has been reported. Whether the effect of aspirin in this
      condition is related to its action on the haemostatic mechanism is unclear, and
      therefore this study aimed to assess the effect of aspirin on some haemostatic
      parameters in patients with chronic venous leg ulcers. A double-blind,
      randomized, placebo-controlled, parallel-group study of haemostatic activity and
      the effect of aspirin was implemented over a 4-month period. Twenty patients with
      venous leg ulcers, and 20 age- and sex-matched controls were studied. Patients
      received enteric-coated aspirin (300 mg) or placebo (one tablet) daily for 4
      months, in addition to standardized local compressive bandaging (Setopress).
      Assessments made at recruitment, and at 2 and 4 months, included measurement of
      total ulcer surface area, haematological and biochemical screening, measurement
      of coagulation times, coagulation factor VIII:C (FVIII:C) and von Willebrand
      factor (vWF), and plasminogen activator inhibitor-1 (PAI-1) levels. Procoagulant
      activity was assessed by a computer-assisted technique, to determine the rate of
      thrombin production in vitro. Patients with venous ulcers had increased levels of
      fibrinogen (P < 0.01), FVIII:C (P < 0.05), vWF (P < 0.05) and PAI-1 antigen (P <
      0.01) compared with controls. Shortening of the coagulation rate, shown by a
      reduction of the time to generate 50% maximal thrombin activity in seconds (T50),
      was seen in patients, in comparison with control subjects (P < 0.05). T50 was
      longer in patients receiving aspirin than those receiving placebo, reflecting
      prolongation of coagulation rate in the aspirin-treated group.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7718460
TI  - Follow-up of skin manifestations in Yu-Cheng children.
AB  - We report an 11-year follow-up study on the dermatological manifestations of Yu
      Cheng children born to mothers who were poisoned by polychlorinated biphenyl
      (PCB)-contaminated cooking oil between 1977 and 1979. Eighty-eight children born
      to these mothers, and 86 matched controls, were examined by one dermatologist.
      Chloracne scars were found in one patient, and there were nail abnormalities in
      about one-third of the exposed patients. Transverse grooves, irregular
      depressions, and koilonychia/nail flattening were significantly more frequent
      than in the control group, based on Fischer's exact test. This study indicates
      that in Yu-Cheng children the nail changes are the most persistent abnormality
      after PCB intoxication, and their occurrence may indicate developmental
      retardation of the fetal nail matrix. Such a finding might also suggest that PCBs
      remaining in the mother could exert an effect on nail growth in children born
      several years after the intoxication event.

PMID- 7718461
TI  - Cryotherapy of common viral warts at intervals of 1, 2 and 3 weeks.
AB  - We studied the efficacy, and time to clearance, of more frequent cryotherapy of
      viral warts, by randomizing 225 patients to receive treatment at 1-, 2- or 3
      weekly intervals. The mean times to clearance of warts in each group were 5.5,
      9.5 and 15 weeks in the weekly, 2-weekly and 3-weekly groups, respectively (P <
      0.01). Cure rates after 3 months correlated with frequency of treatment (P <
      0.05). After 3 months, 43% (66% of non-defaulters) had cleared in the group
      treated weekly, 37% (47%) of the group treated every 2 weeks, and 26% (30%) of
      those treated every 3 weeks. The mean numbers of treatments needed to achieve
      clearance were similar in each group (5.5, 4.75 and 5 treatments). After 12
      treatments, cure rates were similar for all three groups: 43% for the weekly
      treated group (3 months), 48% for the 2-weekly group (6 months), and 44% for the
      3-weekly group (9 months). Percentage cure is related to the number of treatments
      received, and independent of the interval between treatments. A more rapid cure
      may, therefore, be achieved by more frequent treatment.

PMID- 7718462
TI  - Treatment of basal cell carcinoma by dermatologists in the United Kingdom.
      British Association of Dermatologists Audit Subcommittee and the British Society
      for Dermatological Surgery.
AB  - Details of presentation and treatment were obtained prospectively by
      questionnaire for 1366 patients with basal cell carcinoma, first attending under
      the care of 166 consultant dermatologists in the U.K., during a 2-week period.
      One thousand five hundred and ninety-seven tumours were reported in these
      patients (median age 71 years). Most were situated on the head and neck, and
      their median size was 9 mm. Excision was the most common treatment used in 58% of
      tumours, curettage and cautery was used in 24%, cryotherapy in 8%, and
      radiotherapy in 8%. On average, one in four tumours were referred to other
      specialists for treatment (range 0-70%). Very few patients (2%) were referred to
      a combined dermatology/radiotherapy/plastic surgery clinic, calling into question
      its value and availability. There was considerable variation in practices between
      dermatologists, demonstrating a clear need for individual, local audit of the
      management of this common dermatological problem. The data collected in this
      study form a suitable measure with which local performance may be compared.

PMID- 7718463
TI  - Successful treatment and prophylaxis of scalp seborrhoeic dermatitis and dandruff
      with 2% ketoconazole shampoo: results of a multicentre, double-blind, placebo
      controlled trial.
AB  - Pityrosporum ovale appears to play an important role in the pathogenesis of
      seborrhoeic dermatitis. Ketoconazole is an antimycotic agent with a high in vitro
      and in vivo efficacy against P. ovale. We performed a multicentre study to
      investigate the efficacy of ketoconazole 2% shampoo in the treatment and
      prophylaxis of seborrhoeic dermatitis and dandruff. Five hundred and seventy-five
      patients presenting with moderate to severe seborrhoeic dermatitis and dandruff
      of the scalp were treated with 2% ketoconazole shampoo twice weekly for 2-4
      weeks, producing an excellent response in 88%. Of those patients who responded,
      312 were included in a prophylactic phase, lasting 6 months. These patients were
      treated with the active preparation (shampoo containing 2% ketoconazole) once
      weekly, once every other week, alternating with placebo (shampoo without
      ketoconazole), or with placebo only once-weekly. Forty-eight (47%) patients in
      the placebo group experienced a relapse of seborrhoeic dermatitis, compared with
      23 (19%) patients in the active treatment group, and 31 (31%) patients in the
      active/placebo group. The medication was well tolerated in all three groups. We
      conclude that ketoconazole 2% shampoo is highly effective, not only in clearing
      scalp seborrhoeic dermatitis and dandruff, but also in preventing relapse of the
      disease when used prophylactically once weekly.

PMID- 7718464
TI  - Guidelines for the management of chronic venous leg ulceration. Report of a
      multidisciplinary workshop. British Association of Dermatologists and the
      Research Unit of the Royal College of Physicians.
AB  - This document is the product of a multidisciplinary workshop held in November
      1991 between the audit subcommittee of the British Association of Dermatologists
      and the Research Unit of the Royal College of Physicians. Participants included
      dermatologists, vascular surgeons, general practitioners, community nurses and
      physicians involved in care of the elderly. The text is based on papers submitted
      to, and presented and discussed at, the workshop, and on comments received in
      response to subsequent wide dissemination of the proceedings to speciality
      associations. Participants in the workshop, and contributors to the guidelines
      are: Dr B. R. Allen (Nottingham), Sister S. Bainsborough (Exeter), Professor K.
      Burnand (London), Professor D. Burrows (Belfast), Mr M. J. Callam (Bedford), Dr
      G. W. Cherry (Oxford), Dr R. P. R. Dawber (Oxford), Dr W. S. Douglas (Airdrie),
      Dr A. Y. Finlay (Cardiff), Dr D. Gawkrodger (Sheffield), Dr D. J. Gould (Truro),
      Dr A. Hopkins (Royal College of Physicians, London), Dr D. McGibbon (London), Dr
      A. M. Middleton (London), Dr L. Millard (Nottingham), Dr L. Rhodes (Liverpool),
      Professor T. J. Ryan (Oxford), Dr N. B. Simpson (Newcastle), Dr F. D. Skerrett
      (Fowey), Dr J. M. Sowden (Nottingham), Miss L. A. Stone (London), Dr R. Williams
      (Rhyl). Papers presented to the workshop (copies available from the Royal College
      of Physicians of London): 1. Callam M. J. Epidemiology, natural history and rate
      of recurrence of leg ulcers. 2. Ryan T. J. Pathology of venous leg ulcers. 3.
      Gould D. J. Assessment of severity; process and outcomes of care. 4. Millard L.
      The role of infection. 5. Cherry G. Treatment of known effectiveness. 6. Burnand
      K. Indications for surgical treatment.

PMID- 7718465
TI  - Comedonal Darier's disease.
AB  - Darier's disease is an inherited disorder with well-recognized patterns of
      presentation. Lesions commonly affect the trunk and flexures. The diagnosis is
      based on the typical clinical appearance and histology showing acantholytic
      dyskeratosis. We report two unusual cases with prominent nodular, comedonal
      lesions on the face and scalp.

PMID- 7718466
TI  - Disseminated cutaneous Pseudallescheria boydii.
AB  - As increasingly aggressive chemotherapeutic regimens are used to treat
      malignancy, more patients will become susceptible to various opportunistic
      pathogens. Specifically, several fungal organisms previously viewed as relatively
      non-pathogenic are more frequently causing serious disease in these patients.
      Identification of these organisms is of paramount importance, as some are
      relatively resistant to standard antifungal therapies. We report a patient with
      disseminated cutaneous Pseudallescheria boydii, diagnosed from histopathological
      examination and culture of a skin biopsy specimen. Identification of the organism
      was achieved shortly before the patient died. Clinicians must be aware of the
      numerous emerging opportunistic pathogens, which may require special culture
      techniques for diagnosis and varied or combined modes of therapy.

PMID- 7718467
TI  - Delayed hypersensitivity to one low-molecular-weight heparin with tolerance of
      other low-molecular-weight heparins.
AB  - We report a patient who developed infiltrated plaques at the sites of
      subcutaneous injection of a low-molecular-weight heparin. Skin tests and a
      lymphocyte transformation test revealed hypersensitivity to sandoparin and
      heparin sodium. The low-molecular-weight heparins nadroparin and dalteparin were
      subsequently tolerated without adverse effects. Possible risk factors for
      sensitization are discussed.

PMID- 7718468
TI  - Urticarial and anaphylactoid reactions following ethanol intake.
AB  - Ingestion of ethyl alcohol may be associated with a number of adverse reactions.
      Apart from toxicological effects, intolerance syndromes occur, which are caused
      by genetic or acquired defects in alcohol metabolism and are manifest clinically
      as flushing. In addition to these abnormalities, rare cases of generalized
      urticaria and anaphylactoid reactions after ingestion of ethyl alcohol have been
      reported, the pathogenesis of which is still a matter of debate. We describe
      three patients who presented with recurrent generalized urticaria, which
      developed within minutes of consumption of small amounts of ethyl alcohol. Common
      causes of chronic recurrent urticaria were excluded by case history, physical
      examination and laboratory investigations, and by comprehensive allergy testing.
      All patients produce positive prick tests with acetic acid, and developed
      urticaria after oral challenge with small amounts of highly purified ethyl
      alcohol. The symptoms are most probably caused by an intolerance to ethyl alcohol
      or its metabolites, whereas an allergy sensu strictu seems unlikely.

PMID- 7718469
TI  - Staphylococcal scalded skin syndrome in an adult. Influence of immune and renal
      factors.
AB  - We report a case of staphylococcal scalded skin syndrome in a 77-year-old man
      with an infected surgical wound. The patient was immunocompetent and had only
      mildly impaired renal function. The pathogenic and aetiological factors of the
      condition are discussed.

PMID- 7718470
TI  - Erosive pustular dermatosis of the scalp following surgery.
AB  - A 53-year-old woman presented with erosive pustular dermatosis of the scalp 6
      weeks after a bifrontal skin flap and right frontal craniotomy had been performed
      for removal of a suprasellar meningioma. Although some authors consider that
      acute local trauma is a precipitating factor for this condition, we believe that
      this is the first reported case following a neurosurgical procedure.

PMID- 7718471
TI  - Treatment with alpha interferon associated with the development of paraneoplastic
      pemphigus.
AB  - The use of interferon (INF) is usually considered safe, the major side-effect
      being a flu-like syndrome. However, with its ability to alter immune
      responsiveness, INF has been associated with the induction of autoimmune
      diseases. We report a patient with Waldenstrom's macroglobulinaemia who developed
      a generalized blistering eruption after treatment with systemic INF-alpha 2A
      (INF) for multiple skin cancers. The patient's skin showed histological features,
      immunofluorescence findings, and immunoprecipitation diagnostic of paraneoplastic
      pemphigus. Despite aggressive treatment the patient died. In our patient, the use
      of INF was temporally related to the development of paraneoplastic pemphigus.
      Although interferon has been shown to induce other autoimmune diseases, to our
      knowledge this is only the second report of a patient treated with an interferon
      who subsequently developed a fatal autoimmune blistering disorder. Paraneoplastic
      pemphigus is a recently described autoimmune bullous disorder with a poor
      prognosis. The mechanism by which INF triggered the paraneoplastic pemphigus is
      not known.

PMID- 7718472
TI  - Interferon-alpha in combination with corticosteroids improves systemic mast cell
      disease.

PMID- 7718473
TI  - Tamoxifen-induced hair colour change.

PMID- 7718474
TI  - Generalized herpes simplex infection complicating bullous pemphigoid.

PMID- 7718475
TI  - Collision tumour--an unusual skin lesion.

PMID- 7718476
TI  - Mid-dermal elastolysis and pseudoxanthoma elasticum-like papillary dermal
      elastolysis.

PMID- 7718477
TI  - The cellular source of creatine kinase in patients with toxic epidermal
      necrolysis.

PMID- 7718478
TI  - Cutaneous ciliated cyst on the sole of the foot.

PMID- 7718479
TI  - Porokeratotic eccrine ostial and dermal duct naevus.

PMID- 7718480
TI  - Congenital skin fistula with sternal cleft.

PMID- 7718481
TI  - Annual Scientific Meeting of the British Society for Haematology. Brighton,
      United Kingdom, 3-6 April 1995. Abstracts.

PMID- 7718482
TI  - Response of heat shock element within the human HSP70 promoter to mutated p53
      genes.
AB  - Recent studies have demonstrated that mutation of the p53 gene caused a gain of
      new functions such as transforming activation, binding to heat shock cognate
      protein 70 and/or transactivation of a variety of promoters. In the course of
      seeking the biochemical basis for the gain of these functions, we have noticed
      the correlation between transforming activity of different mutated p53 genes and
      their transactivational activity on the human heat shock protein 70 promoter.
      Analysis of 5' deletion constructs of the heat shock protein 70 promoter showed
      that some specific elements within the heat shock domain containing two heat
      shock elements (HSEs) could respond to mutant p53 species but not basic promoter
      elements such as the TATA box, CCAAT box, and GC box. Subsequently, we identified
      the HSE as a responsive element using reporter constructs of minimal promoter
      containing synthetic proximal HSE, distal HSE, or GC/CCAAT box. Further analysis
      using in vitro mutagenesis of HSE suggests that HSE with heat shock factor
      binding ability is required for transactivation of the heat shock protein 70
      promoter by mutated p53 genes.

PMID- 7718483
TI  - Reconstitution of mice with bone marrow cells expressing the SCL gene is
      insufficient to cause leukemia.
AB  - Rearrangement or translocation of the SCL gene is the most common genetic
      abnormality observed in human T-cell acute lymphocytic leukemia and results in
      the aberrant expression of SCL. To examine the oncogenic potential of this gene,
      an SCL-retrovirus was used to infect mouse bone marrow cells, which were then
      used to reconstitute C57/BL6 mice. Expression of SCL did not perturb the
      composition nor number of day 12 or day 13 colony forming unit-spleen. In total,
      141 mice reconstituted with SCL-infected bone marrow and 103 control-mice were
      monitored for up to 2 years with no difference in survival, hematocrit, white
      cell count, or differential white cell count. As expected, from day 200 onwards,
      mice died due to radiation-induced thymomas; SCL provirus was not detected in
      these tumors. Thus, despite SCL being strongly implicated in the development of
      human leukemia, its enforced expression in mice using a retrovirus and bone
      marrow reconstitution was insufficient to generate leukemia.

PMID- 7718484
TI  - Transformation-resistant mos revertant is unable to activate MAP kinase kinase in
      response to v-mos or v-raf.
AB  - To study the mechanism by which v-mos induces cell transformation, we generated a
      transformed rat cell line (DTM) containing two functional copies of mos, one
      encoding the p37v-mos of the m1 wild-type strain of Moloney murine sarcoma virus
      (Mo-MuSV) and the other the p85gag-mos fusion protein of the ts110 mutant of
      Moloney murine sarcoma virus. Subsequently, we isolated a revertant cell line (F
      1) following transfection of DTM with a mutant retroviral construct (pIC4Neo)
      carrying a selectable marker. Like DTM, the F-1 revertant contained two
      integrated copies of v-mos, expressed mos containing viral RNA, and contained
      rescuable transforming viruses. The revertant did not grow in soft agar, showed a
      greatly reduced ability to form tumors in nude mice, and exhibited organized
      tubulin and actin structures similar to those found in normal cells. Revertant
      cells were resistant to retransformation by v-mos and v-raf but could be
      retransformed by v-ras. MAP kinase (ERK-2) and MAP kinase kinase (MKK-1)
      activity, which are constitutively elevated in v-mos- and v-raf-transformed
      cells, exhibits levels in the F-1 revertant similar to those seen in
      nontransformed cells. F-1 and normal REF-1 cells express elevated levels of
      protein phosphatases in comparison to DTM cells. In vivo treatment with okadaic
      acid, a potent protein phosphatase inhibitor, leads to an increase in MKK-1 and
      MAP kinase activity in F-1 cells but not in REF-1. The results support the
      hypothesis that mos acts through the MAP kinase cascade (MKK-1 and ERK-2) to
      induce cell transformation and that blocking v-mos activation of that cascade
      (possibly because of increased levels of phosphatase) prevents transformation.

PMID- 7718485
TI  - Lymphoma models for B-cell activation and tolerance: anti-immunoglobulin M
      treatment induces growth arrest by preventing the formation of an active kinase
      complex which phosphorylates retinoblastoma gene product in G1.
AB  - The product of the retinoblastoma gene, RB-1, is the prototype of a class of
      tumor suppressor genes that is expressed in most mammalian cells. The RB protein
      is phosphorylated in a cell cycle-dependent manner and is modulated during
      cellular differentiation. We have shown previously that anti-immunoglobulin M
      (anti-mu) treatment of WEHI-231 and CH31 B-lymphoma cells caused cell cycle
      blockade and apoptosis. In such arrested cells, pRB was predominantly in the
      underphosphorylated (active) form, in contrast to hyperphosphorylated pRB in
      control log phase cells. Herein we examine the modulation of pRB phosphorylation
      by anti-mu and its effect on a cyclin:kinase complex that can act on pRB in
      murine B-lymphoma cells. In unsynchronized B-lymphoma cells, anti-mu cross
      linking of membrane immunoglobulin M leads to an accumulation of the
      hypophosphorylated form of pRB, a decrease in the abundance of one form of cyclin
      A, and inhibition of cyclin A and cdk2-associated kinase activity. Using
      centrifugal elutriation, we also show that anti-mu treatment prevents the
      phosphorylation of the retinoblastoma gene product only when added in early G1.
      In addition, there is a critical point after which membrane immunoglobulin M
      cross-linking is no longer effective at preventing this process. We suggest that
      anti-mu-mediated growth arrest is due to the direct or indirect inactivation of
      an active kinase complex capable of pRB phosphorylation.

PMID- 7718486
TI  - The effect of oncogenes on the growth and differentiation of oligodendrocyte type
      2 astrocyte progenitor cells.
AB  - Oncogenes represent altered versions of cellular genes instrumental for control
      of cell proliferation and differentiation. Several oncogenes have been implicated
      in glial cell transformation and immortalization in culture (myc, src, mos, ras,
      and SV40 large T antigen). The purpose of this study is to further our
      understanding of glial cell neoplasia by investigating the effect of oncogenes on
      the growth and differentiation of central nervous system glial progenitor cells
      from the oligodendrocyte type 2 astrocyte (O-2A) lineage. This progenitor cell
      differentiates into an oligodendrocyte or a type-2 astrocyte according to
      environmental cues. Drug-selectable retroviral vectors were used to introduce
      oncogenes either alone or in combination into primary cultures of rat O-2A cells.
      Established O-2A progenitor cell lines were only obtained after infection with c
      myc or SV40 large T antigen, suggesting that among the oncogenes tested only
      these were capable of immortalizing O-2A progenitor cells. The O-2A/c-myc and O
      2A/temperature-sensitive SV40 large T antigen cell lines retained the capacity to
      differentiate into oligodendrocytes and type-2 astrocytes, thereby providing an
      opportunity to study the effects of oncogene cooperation on the phenotype of O-2A
      lineage cells. Superinfection of these cells lines with retroviruses encoding ras
      or src led to abnormalities of differentiation whose nature and severity depended
      on the combination of cooperating oncogenes and/or the levels of expression
      obtained. This study demonstrates that oncogene-modified glial cell lines provide
      an amenable and unique model system to study differentiation in the central
      nervous system and the genetic changes involved in the development of glioma.

PMID- 7718487
TI  - Arginine-vasopressin induces differentiation of skeletal myogenic cells and up
      regulation of myogenin and Myf-5.
AB  - The neurohypophyseal nonapeptide arginine8-vasopressin (AVP) induces
      phosphoinositide turnover and calcium and pH changes in skeletal myogenic cells
      in culture. In order to investigate the effect of AVP on skeletal myogenesis, we
      examined the effect of this hormone on proliferating mononucleated L6 myoblast
      cultures. Addition of AVP to the medium resulted in the formation of much larger
      myotubes than those formed in its absence and in a significant increase (2.2
      fold) of the percentage of fusion within 3-4 days of treatment. The effect of AVP
      was dose dependent, in the 10 nM to 1 microM range, and was observed also in
      primary cultures of mouse satellite cells. The rate of growth of L6 cells was not
      affected by AVP treatment. The induction of morphological differentiation by AVP
      correlated with an increased expression of muscle-specific gene products, such as
      myosin, and an increased number of acetylcholine receptor sites. The accumulation
      of mRNA transcripts of the acetylcholine receptor subunits was also enhanced by
      AVP. The mechanism involved in the myogenic action of AVP was investigated. Using
      AVP-related peptides and antagonists, we found that a specific chemical structure
      is required and that V1 receptors probably mediate the effect on myogenesis.
      Expression of muscle-specific transcription factor genes Myf-5 and myogenin and
      their products are strongly upregulated by AVP. Our findings support the
      hypothesis that AVP may represent a novel physiological modulator of skeletal
      muscle differentiation through its action on muscle regulatory genes.

PMID- 7718488
TI  - Involvement of the tumor suppressor gene p53 in tumor necrosis factor-induced
      differentiation of the leukemic cell line K562.
AB  - The cDNA of the human wild-type p53 tumor suppressor gene was constitutively
      overexpressed in the leukemic cell line K562 (which lacks detectable amounts of
      p53 protein) in order to investigate the consequences for growth and
      differentiation. Several stable clones were established by transfection of the
      expression vector pc53SN3. Expression of p53 protein was characterized by
      biosynthetic labeling and immunoprecipitation with the monoclonal antibodies pAb
      1801 (reacting with wild-type and mutant human p53), pAb 240 (reacting with
      mutant human p53) and pAb 1620 (reacting with wild-type human p53). All clones
      which were 1801+, 240-, 1620- or 1801+, 240-, 1620+ were defined as "wild-type
      like p53-expressing" clones. Our results show that expression of p53 protein is
      compatible with continuous proliferation of K562 cells. The growth
      characteristics of wild-type-like p53-expressing clones did not differ from that
      of control clones. However, the former were more sensitive than p53-negative
      control clones to growth inhibition by tumor necrosis factor (TNF), a cytokine
      with a potential role in growth and differentiation of myeloid leukemic cells. In
      addition, a 2- to 4-fold increase of the amount of hemoglobin, a marker of
      erythroid differentiation, was observed when wild-type-like p53 protein
      expressing clones were incubated with TNF. This suggests that differentiation is
      the mechanism responsible for the increased TNF sensitivity of these clones. Our
      results support a role for p53 in mediating growth inhibitory and differentiation
      inducing signals by TNF.

PMID- 7718489
TI  - Ki-ras oncogene interferes with the expression of cyclic AMP-dependent promoters.
AB  - The expression of thyroglobulin and other thyroid-specific markers depends upon
      the activation of protein kinase A (PKA) by cyclic AMP. A rat thyroid cell line
      dedifferentiates when transformed with Ki-ras oncogene. The decrease in
      thyroglobulin gene expression parallels a reduction in the level of PKA nuclear
      catalytic subunit. We find that the activity of cAMP-responsive elements and
      thyroglobulin promoters is down-regulated in Ras-transformed cells. Transcription
      of a third cAMP-regulated gene, H-ferritin, is similarly reduced. cAMP-responsive
      element and H-ferritin expression were stimulated when intracellular cAMP levels
      were increased. Reactivation of the thyroglobulin promoter required depletion of
      PKC in addition to increased cAMP. We also find that v-Ras activation leads to a
      significant increase in membrane-bound PKC. These data support the idea that v
      Ras via PKC inhibits the transmission of cAMP-PKA signals to the nucleus. We
      suggest that the thyroglobulin promoter is more sensitive than other cAMP
      dependent promoters to reduced nuclear levels of PKA catalytic subunit.

PMID- 7718490
TI  - A transgenic mouse model for lung adenocarcinoma.
AB  - Lung cancer is a leading cause of tumor-related deaths in humans but its origin
      and development are poorly understood. To study the biology of these tumors,
      appropriate animal and cell culture models will be of eminent importance.
      Uteroglobin is a marker protein for the nonciliated epithelial Clara cells lining
      the respiratory and terminal bronchioli of the lung. We have used the promoter
      and 5'-flanking sequences of the rabbit uteroglobin gene to target expression of
      the SV40 T antigen to the lung of transgenic mice. All transgenic founders as
      well as the descendants from an established line, UT7.1, developed multifocal
      bronchioloalveolar adenocarcinomas originating from Clara cells. At least three
      different stages in tumor development with progressive loss of the differentiated
      phenotype can be distinguished by immunohistochemical data and in situ
      hybridization. Only in the initial stage did bronchiolar cells express both
      uteroglobin and SV40 T antigen, whereas at later stages, only SV40 T antigen was
      detected, and the most advanced tumors were negative for both proteins. Starting
      from the lungs of UT7.1 mice, a bronchiolar cell line was established that
      maintains the features of differentiated Clara cells. This system provides a
      useful model for further studying the development and progression of lung
      adenocarcinomas in vivo and in vitro.

PMID- 7718491
TI  - Neuropeptide Y immunoreactivity of a projection from the lateral thalamic nucleus
      to the optic tectum of the leopard frog.
AB  - Using rhodamine-labelled latex beads as a retrograde tracer, we have shown that a
      subset of the neurons projecting from the lateral thalamic nucleus to the optic
      tectum of the leopard frog are neuropeptide Y-like immunoreactive (NPY-IR). In
      juvenile frogs, approximately twice as many lateral thalamic nucleus cells from
      this area project to the ipsilateral tectum as project to the contralateral
      tectum. NPY-IR cells make up 25% of the projection to the ipsilateral tectum and
      13% of the projection to the contralateral tectum. The ipsilateral NPY-IR
      projection from the lateral nucleus was present in tadpoles and was similar in
      its characteristics to that found in the juvenile frog. However, the
      contralateral tectal projection was virtually nonexistent in these animals. The
      results of these experiments suggest that NPY from the lateral nucleus is
      released into the ipsilateral tectal neuropil in both the developing and adult
      frog.

PMID- 7718492
TI  - Spatial structure of chromatically opponent receptive fields in the human visual
      system.
AB  - This study investigates the receptive-field structure of mechanisms operating in
      human color vision, by recording visual evoked potentials (VEPs) to multiharmonic
      gratings modulated either in luminance or color (red-green). Varying the Fourier
      phase of the harmonics from 0 deg to 90 deg produced a family of stimulus
      profiles that varied from lines to edges. The stimuli were contrast reversed to
      elicit steady-state VEPS, and also randomly jittered (at a higher temporal
      frequency than the contrast reversal) to ensure that the evoked response resulted
      from the polarity reversal, rather than from local variation of luminance or
      color. Reliable VEPs were recorded from both luminance and chromatic stimuli at
      all phases, suggesting that the mechanisms sensitive to chromatic contrast and
      those sensitive to luminance contrast have both symmetric and asymmetric
      receptive fields. Contrast thresholds estimated by extrapolation of the contrast
      response curves were very similar to psychophysical thresholds for phase
      discrimination, suggesting that the VEP response is generated by mechanisms
      mediating phase discrimination. The results support the idea that human color
      mechanisms have receptive fields with a variety of spatial symmetries (including
      odd- and even-symmetric fields) and that these mechanisms may contribute to phase
      discrimination of chromatic stimuli in a similar way to what has been suggested
      for luminance vision.

PMID- 7718493
TI  - Synaptic circuitry of serotonin-synthesizing and serotonin-accumulating amacrine
      cells in the retina of the cane toad, Bufo marinus.
AB  - The synaptic connections of amacrine cells synthesizing or accumulating serotonin
      in the retina of the cane toad, Bufo marinus, were studied by using preembedding
      double-labeling electron-microscopic immunocytochemistry. The binding sites of an
      anti-serotonin antibody were revealed by the diaminobenzidine reaction, whilst a
      colloidal gold-conjugated secondary antibody was used to detect an antibody to
      phenylalanine hydroxylase. Since the latter antibody recognizes tryptophan 5
      hydroxylase, one of the synthesizing enzymes for serotonin, as well as tyrosine
      hydroxylase, the rate-limiting enzyme for catecholamine synthesis, the double
      labeling of the present study enabled us to identify three groups of labeled
      profiles at the ultrastructural level. The profiles of serotonin-synthesizing
      amacrine cells contained both diaminobenzidine reaction product and colloidal
      gold particles, whilst those of serotonin-accumulating and dopaminergic amacrine
      cells contained only diaminobenzidine reaction product or colloidal gold
      particles, respectively. The synapses of serotonin-synthesizing or serotonin
      accumulating amacrine cells were distributed all through the inner plexiform
      layer of the retina. The profiles of serotonin-synthesizing amacrine cells
      predominantly received synapses from, and made synapses onto, unlabeled amacrine
      cell dendrites. They also received synapses from, and made synapses onto, bipolar
      cell terminals. They also made synapses onto presumed ganglion cell dendrites.
      However, the profiles of serotonin-accumulating cells made synapses only with
      unlabeled amacrine cell processes. There were close contacts between the profiles
      of serotonin-synthesizing and serotonin-accumulating amacrine cells. No synaptic
      relationships were observed between dopaminergic and serotonin-synthesizing or
      serotonin-accumulating amacrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718494
TI  - Spatio-temporal receptive-field structure of phasic W cells in the cat retina.
AB  - The spatio-temporal receptive-field structure of 54 phasic W cells in cat retinas
      has been examined using the reverse-correlation method of Jones and Palmer
      (1987). Within this sample, 12 cells had on-center, 16 off-center, and 26 on-off
      receptive fields. Three of the on-center and seven of the on-off cells were
      directionally selective. Forty percent of the cells in this sample had local
      receptive fields consisting of two or more distinct subregions. However, no
      correlation was observed between the number of subregions in the local receptive
      field and other response properties such as center sign or direction selectivity.
      In all cases, individual subregions, including those in on-off cells, appear to
      be produced by a half-wave rectification of the input signal. For 76% of the
      cells, these local receptive fields were contained within large suppressive
      fields which could be seen to extend for at least 10 deg in all directions with
      no apparent spatial structure. The mechanism producing the suppressive field also
      appears to involve a rectification of the input signal, and has a relatively high
      spatial resolution. Furthermore, the suppressive field itself is only responsive
      to moving or flickering stimuli; large, stationary gratings have no effect on the
      output of the local receptive-field mechanism. Thus, the overall receptive-field
      organization of these cells is particularly well suited for detecting local
      motion. The remaining 24% of cells in the sample lacked suppressive fields, and
      consequently responded well to large moving stimuli, but these cells were
      otherwise similar in their receptive-field properties to cells with suppressive
      fields. The significance of these properties is discussed in the context of the
      projections of phasic W cells to the superior colliculus and accessory optic
      system.

PMID- 7718495
TI  - Are neurons in cat posteromedial lateral suprasylvian visual cortex orientation
      sensitive? Tests with bars and gratings.
AB  - There is controversy in the literature concerning whether or not neurons in the
      cat's posteromedial lateral suprasylvian (PMLS) visual cortex are orientation
      selective. Previous studies that have tested cells with simple bar stimuli have
      found that few, if any, PMLS cells are orientation selective. Conversely, studies
      that have used repetitive stimuli such as gratings have found that most or all
      PMLS cells are orientation selective. It is not known whether this difference in
      results is due to the stimuli used or the laboratories using them. The present
      experiments were designed to answer this question by testing individual PMLS
      neurons for orientation sensitivity with both bar and grating stimuli. Using
      quantitative response measures, we found that most PMLS neurons respond well
      enough to stationary flashed stimuli to use such stimuli to test for orientation
      sensitivity. On the basis of these tests, we found that about 85% of the cells
      with well-defined receptive fields are orientation sensitive to flashed gratings,
      and a similar percentage are orientation sensitive to flashed bars. About 80% of
      the cells were orientation sensitive to both types of stimuli. The preferred
      orientations typically were similar for the two tests, and they were orthogonal
      to the preferred direction of movement. The strength of the orientation
      sensitivity (measured as the ratio of discharge to the preferred and nonpreferred
      orientations) was similar to both types of stimuli. However, the width of the
      orientation tuning curves was systematically broader to bars than to gratings.
      Several hypotheses are considered as to why previous studies using bars failed to
      find evidence for orientation sensitivity. In addition, a mechanism for the
      difference in orientation tuning to bars and gratings is suggested.

PMID- 7718496
TI  - Contrast sensitivity in dyslexia.
AB  - Contrast sensitivity was determined for dyslexic and normal readers. When testing
      with temporally ramped (i.e. stimuli with gradual temporal onsets and offsets)
      gratings of 0.6, 4.0, and 12.0 cycles/deg, we found no difference in contrast
      sensitivity between dyslexic readers and controls. Using 12.0 cycles/deg gratings
      with transient (i.e. abrupt) onsets and offsets, we found that dyslexic
      individuals had, compared to controls, markedly inferior contrast sensitivity at
      the shortest stimulus durations (i.e. 17, 34, and 102 ms). This deficit may
      reflect more sluggish temporal summation. There was no difference in sensitivity
      to 0.6 cycles/deg gratings with transient onsets and offsets. Under these
      conditions, the two groups showed a consistent and equal increase in sensitivity
      relative to the ramped baseline condition at 0.6 cycles/deg at the longer
      stimulus durations. This demonstrates that dyslexic readers have no deficit in
      their ability to detect stimulus transients, a finding which appears to be
      inconsistent with a transient system deficit. That detection of the low-frequency
      stimuli was mediated by the transient system is further indicated by the fact
      that these stimuli were more susceptible to forward masking than were the high
      frequency stimuli. The effects of masking of both high and low spatial-frequency
      stimuli were about equal for dyslexic readers and controls. This is not in
      agreement with the transient system deficit theory, according to which one would
      expect there to be less masking of high spatial-frequency stimuli in the case of
      dyslexic readers.

PMID- 7718497
TI  - Dendritic integration in ganglion cells of the mudpuppy retina.
AB  - Computer simulations were carried out to evaluate the influence of varying the
      membrane resistance (Rm) on the dendritic integration capacity of three classes
      of ganglion cells in the mudpuppy (Necturus maculosus) retina. Three broadly
      different morphological classes of ganglion cells were selected for this study
      and represent the range of dendritic tree sizes found in the ganglion cell
      population of this species. Simulations were conducted on anatomical data
      obtained from cells stained with horseradish peroxidase; each cell was traced,
      using a computer as an entry device and later converted to a compartmental
      (electrical) representation of the cell. Computer-simulation analysis used a time
      variant conductance change which was similar in waveform to light-activated
      bipolar cell input. The simulated membrane resistance for each cell varied
      between 5000 and 100,000 omega cm2, and conductance changes were introduced into
      different regions of the soma-dendritic tree to evaluate dendritic integration
      efficiency. When higher values of Rm are used, even the largest cells become
      electronically compact and attenuation of voltage responses is minimized from
      distal to soma regions. Responses were less attenuated from proximal to distal
      regions of the cell because of the favorable impedance matching, and because less
      current is required to polarize small "sealed" dendritic terminations. Steady
      state responses integrate more effectively than transient responses, particularly
      when Rm is high, since transient responses were more attenuated by the membrane
      capacitance. The possibility that Rm is a dynamic property of retinal ganglion
      cells is discussed in view of the functional organization of dendritic
      integration efficiency as Rm fluctuates from low to high values.

PMID- 7718498
TI  - Receptive-field properties of displaced starburst amacrine cells change following
      axotomy-induced degeneration of ganglion cells.
AB  - Starburst amacrine cells in the rabbit retina were labeled following an
      intraocular injection of the fluorescent dye, 4,6,diamidino-2-phenylindole
      (DAPI). From each eye a strip of retina was removed, mounted on a platform
      beneath an epifluorescence microscope, and superfused with a physiological
      solution. The tip of a tungsten microelectrode (for extracellular recording) was
      visually positioned near the cell body of a DAPI-labeled starburst amacrine cell
      that was located in the ganglion cell layer. Light-evoked responses from the
      displaced starburst amacrine cells were studied in normal retinas and in retinas
      that had received a small electrolytic lesion near the optic disk 5-9 months
      beforehand. In normal retinas, a small spot of light centered over the receptive
      field of a displaced starburst amacrine cell in nearly all cases evoked a brief
      burst of spikes only at light onset. When stimulated with a large spot or an
      annulus of light, many cells gave a small burst of spikes at light offset. In
      lesioned retinas, the light responses of displaced starburst amacrine cells were
      recorded in areas of the retina where ganglion cells had degenerated. All cells
      responded with a large burst of spikes at the onset and offset of a small,
      centered spot of light. Large spots and annuli of light also evoked robust ON/OFF
      responses from these cells. The results from this study show that the receptive
      field properties of displaced starburst amacrine cells change following axotomy
      induced degeneration of ganglion cells. This finding indicates that changes in
      either synaptic transmission or the membrane properties of neurons occur in the
      retina following degeneration of ganglion cells.

PMID- 7718499
TI  - Preproenkephalin messenger RNA-containing amacrine cells in the chicken retina
      identified with in situ hybridization histochemistry.
AB  - Enkephalin peptides are present in the retina of several vertebrate species. In
      the avian retina, enkephalin immunoreactivity is primarily localized to a
      population of amacrine cells. In the present study, we determined the
      localization of cells expressing preproenkephalin (PPE) mRNA, which encodes the
      precursor of enkephalin peptides, in adult as well as in embryonic chicken
      retinas. The localization of PPE mRNA-expressing cells to the proximal inner
      nuclear layer (INL) in the adult chicken retina is similar to that of enkephalin
      immunoreactive cells observed in previous studies, indicating that amacrine cells
      expressing PPE mRNA synthesize Met5- and Leu5-enkephalin peptides and related
      extended forms. Specific hybridization signal is absent in retinas at embryonic
      day (E) 11, but it is detected in retinas at E 15 and at hatching. PPE mRNA
      expressing cells at these ages are located in the proximal INL, and they can be
      classified as amacrine cells on the basis of their soma size and laminar
      position. These findings confirm and extend previous observations on the presence
      of opioid peptides in amacrine cells of the chicken retina. The presence of PPE
      mRNA at embryonic ages, together with the evidence that enkephalins influence
      developmental processes, suggests that these peptides modulate retinal maturation
      in birds.

PMID- 7718500
TI  - Pharmacological inactivation of pretectal nuclei reveals different modulatory
      effects on retino-geniculate transmission by X and Y cells in the cat.
AB  - The modulatory influence of pretectal neurons on retino-geniculate transmission
      in the cat was studied by cross-correlation analysis of single-unit activity
      simultaneously recorded from the dorsal lateral geniculate nucleus (dLGN) and the
      pretectum (PT) and with reversible inactivation of the PT by GABA
      microiontophoresis during simultaneous visual stimulation of PT and dLGN neurons.
      Visually induced population activity in PT nuclei was achieved by a moving (or
      counterphasing) grating which was presented in the background of the light spot
      used to stimulate the dLGN neuron. As a control, the light spot was presented on
      a stationary grating to avoid stimulation of PT neurons but to yield the same
      illumination of the background. Extracellularly recorded dLGN relay cells of the
      X- and Y-type were found to be differentially affected by the PT-dLGN projection.
      During visual stimulation of PT cells, X cells were strongly inhibited and this
      effect was significantly reduced during PT inactivation. By contrast, the visual
      responses of most Y cells were affected neither by PT stimulation nor by PT
      inactivation. In addition, the temporal structure of spike patterns during the
      light response was examined with autocorrelograms and spike-interval
      distributions. X-on cells often exhibited a multimodal interval distribution and
      oscillatory type of activity. During stimulation of the PT interval distributions
      changed in a characteristic manner and oscillations disappeared. Both effects
      could be almost totally cancelled by PT inactivation. By contrast, the temporal
      structure of Y-cell responses was not affected. Our results demonstrate for the
      first time a pretectal modulation of retino-geniculate transmission in cat dLGN
      which is clearly different for X and Y cells. This influence seems to be mediated
      via (inhibitory) interneurons, since we found no indication for a direct coupling
      between PT and dLGN units. This projection might contribute to the well-known
      phenomenon of saccadic suppression.

PMID- 7718501
TI  - Neuronal activity in primate visual cortex assessed by immunostaining for the
      transcription factor Zif268.
AB  - It is now well established that environmental signals mediated via
      neurotransmitters and hormones can induce responses in cells which involve a
      cascade of receptors, G proteins, and second messengers. These in turn can induce
      transcription factors which regulate long-term changes in gene expression. It has
      been proposed that the stimulus-transcription coupling properties of these DNA
      binding proteins can be exploited to visualize activated neurons by way of
      immunostaining. We have used standard immunohistochemical techniques to detect
      the expression of one specific transcription factor, Zif268, in the visual cortex
      (area 17, V1) of vervet monkeys (Cercopithecus aethiops). Immunopositive neurons
      were present in large numbers throughout the visual cortex of the normal animal,
      being concentrated in layers 2/3 and 6 and at moderate levels in 4C beta and 5.
      To determine if Zif268 expression was affected by visual stimulation in the
      monkey, we restricted light input to one eye with the aim of revealing ocular
      dominance columns in striate cortex. We found that short-term monocular
      deprivation induced either by enucleation, intravitreal TTX injection, or eyelid
      suturing resulted in dramatic changes in Zif268 levels, revealing vertically
      oriented columns of reduced Zif268 staining interdigitated with columns of normal
      expression. Furthermore, these columns were discernible after just 2 h of
      monocular blockade. A comparison of the ocular-dominance pattern obtained with
      Zif268 immunostaining and cytochrome oxidase histochemistry in long-term
      monocularly deprived animals showed a coincident reduction of both markers along
      columns that were precisely aligned in adjacent sections, indicating that Zif268
      expression is restricted to cortical regions of high metabolic activity.
      Simultaneous immunostaining for Zif268 and the calcium-binding proteins calbindin
      and parvalbumin showed a negative correlation, suggesting that the Zif268 protein
      may be expressed selectively within excitatory neurons. A similar approach with
      immunostaining for neurofilament and microtubule-associated proteins (SMI-32 and
      MAP2) revealed pyramidal neurons which were regularly found to contain a Zif268
      positive nucleus. Furthermore, confocal images of lucifer yellow filled neurons
      possessing Zif268-positive nuclei all showed pyramidal morphology. Taken
      together, these results point to activity-dependent expression of Zif268 within a
      subset of excitatory neurons.

PMID- 7718502
TI  - Nerve growth factor preserves behavioral visual acuity in monocularly deprived
      kittens.
AB  - Recent electrophysiological and anatomical experiments in rats and cats have
      shown that treatment with the neurotrophic factor-nerve growth factor (NGF)
      prevents the effects of monocular deprivation (MD) at the level of visual cortex
      and lateral geniculate nucleus. We tested whether NGF treatment was effective in
      preventing MD effects on visual behavior of monocularly deprived kittens.
      Behavioral visual acuity was measured in kittens that had been monocularly
      deprived and treated intraventricularly with NGF for 2 weeks during the critical
      postnatal period. The detrimental effects of MD on behavioral visual acuity were
      found to be largely prevented by NGF treatment.

PMID- 7718503
TI  - The morphology and physiology of a "mini-ommatidium" in the median optic nerve of
      Limulus polyphemus.
AB  - Examination of the Limulus median optic nerve with low-magnification light
      microscopy allows clear visualization of an ultraviolet-sensitive mini-ommatidium
      enshrouded by pigment cells, glial cells, and guanophores. Serial 1-micron
      sections of median optic nerves containing mini-ommatidia revealed the presence
      of a single, heavily pigmented photoreceptor (retinular) cell and a single,
      unpigmented arhabdomeric cell. Computer-assisted serial reconstructions from 1
      micron sections confirmed the presence of two cells, each bearing a nucleus, and
      two axons leaving the mini-ommatidium. The retinular cell is morphologically
      similar to retinular cells from the median and lateral eyes. Its rhabdomere
      appears to be a continuous sheet of microvilli with much infolding. The structure
      of the arhabdomeric cell is nearly identical to those found in the median
      ocellus. As in other photoreceptors in Limulus, the retinular cell of the mini
      ommatidium is innervated by efferent fibers from the brain. Each mini-ommatidium
      generates a single train of nerve impulses in response to light, presumably from
      the arhabdomeric cell. Measurement of the spectral sensitivity of the mini
      ommatidium based upon a constant-response criterion indicated that the retinular
      cell is maximally sensitive to near ultraviolet light with lambda max = 380 nm.
      Comparison of intensity-response functions revealed that those of the mini
      ommatidium are significantly steeper than those of the ocellus almost certainly
      as the result of neural processing in the ocellus which is absent in the mini
      ommatidium.

PMID- 7718504
TI  - Contrast coding by cells in the cat's striate cortex: monocular vs. binocular
      detection.
AB  - Many psychophysical studies of various visual tasks show that performance is
      generally better for binocular than for monocular observation. To investigate the
      physiological basis of this binocular advantage, we have recorded, under
      monocular and binocular stimulation, contrast response functions for single cells
      in the striate cortex of anesthetized and paralyzed cats. We applied receiver
      operating characteristic analysis to our data to obtain monocular and binocular
      neurometric functions for each cell. A contrast threshold and a slope were
      extracted from each neurometric function and were compared for monocular and
      binocular stimulation. We found that contrast thresholds and slopes varied from
      cell to cell but, in general, binocular contrast thresholds were lower, and
      binocular slopes were steeper, than their monocular counterparts. The binocular
      advantage ratio, the ratio of monocular to binocular thresholds for individual
      cells, was, on average, slightly higher than the typical ratios reported in human
      psychophysics. No single rule appeared to account for the various degrees of
      binocular summation seen in individual cells. We also found that the proportion
      of cells likely to contribute to contrast detection increased with stimulus
      contrast. Less contrast was required under binocular than under monocular
      stimulation to obtain the same proportion of cells that contribute to contrast
      detection. Based on these results, we suggest that behavioral contrast detection
      is carried out by a small proportion of cells that are relatively sensitive to
      near-threshold contrasts. Contrast sensitivity functions (CSFs) for the cell
      population, estimated from this hypothesis, agree well with behavioral data in
      both the shape of the CSF and the ratio of binocular to monocular sensitivities.
      We conclude that binocular summation in behavioral contrast detection may be
      attributed to the binocular superiority in contrast sensitivity of a small
      proportion of cells which are responsible for threshold contrast detection.

PMID- 7718505
TI  - Asymmetric retinal growth in the adult teleost green sunfish (Lepomis cyanellus).
AB  - Previous studies on fish retina have suggested that a curved, non-fused embryonic
      fissure is associated with, and perhaps caused by, asymmetric growth along the
      retina's marginal germinal zone (where neurons and Muller glia are added
      appositionally throughout life). In this report retinal growth was measured
      directly in adult green sunfish (Lepomis cyanellus), which has a curved, non
      fused embryonic fissure. Growth was asymmetric in both small and large fish:
      ventral and nasal retina grew more than temporal and dorsal retina. This
      asymmetry was due to different net rates of cellular addition, rather than
      differential passive expansion. The absolute rates of retinal growth in the
      centroperipheral direction were roughly exponential functions of fish size-
      smaller fish grow faster than large fish--but the area of new retina added per
      unit time did not vary with fish size. Visual implications of asymmetric retinal
      growth are evaluated.

PMID- 7718506
TI  - Activation signals are delivered through two distinct epitopes of CD100, a unique
      150 kDa human lymphocyte surface structure previously defined by BB18 mAb.
AB  - We have previously reported the identification of a glycoprotein dimer, now
      termed CD100, at the lymphocyte cell surface using a mAb termed BB18. In the
      present study we isolated a second mAb, termed BD16, recognizing another epitope
      of this 150 kDa structure. We show that interaction with individual mAb triggers
      differential functional effects on peripheral blood lymphocytes (PBL) and
      purified T cells. In particular and of the utmost interest, BD16 mAb strongly
      inhibits CD3 induced PBL proliferation while it dramatically increases the CD2
      induced proliferation. In contrast, after T cell purification, BD16 mAb increases
      both CD2 and CD3 induced proliferation. It has to be noted that perturbation of
      the same 150 kDa surface molecule with BB18 mAb exerts no effect on CD2 and CD3
      induced proliferations, while inducing a strong lymphocyte proliferation in the
      presence of submitogenic concentrations of phorbol myristate acetate.

PMID- 7718507
TI  - Superantigen-reactive T cells that display an anergic phenotype in vitro appear
      functional in vivo.
AB  - Clonal deletion and/or inactivation establishes tolerance to self antigens.
      Endogenous and exogenous (bacterial) superantigens, like the staphylococcal
      enterotoxins, induce ligand-specific clonal anergy in vivo and thus are believed
      to mirror aspects of post-thymic tolerance mechanisms in mature peripheral T
      cells. Here we analyzed the level of anergy of ligand-responsive V beta 8+ T
      cells from staphylococcal enterotoxin B (SEB)-primed mice in vivo and in vitro.
      Upon in vitro restimulation with SEB, CD4+V beta 8+ and CD8+V beta 8+ T cells
      failed to produce IL-2. However, functional IL-2 receptors were triggered, since
      supplementation with IL-2 induced clonal growth in virtually all CD4+V beta 8+
      and CD8+V beta 8+ T cells as determined by limiting dilution analyses. Thus in
      vitro unresponsiveness of lymphocytes from SEB-primed mice reflects the inability
      of SEB-reactive V beta 8+ T cells to produce IL-2. Surprisingly, anergy as
      defined in vitro was at variance with that in vivo. Following further challenge
      with SEB, systemic and acute lymphokine production (including IL-2 and tumor
      necrosis factor) occurred with almost identical peak values and kinetics to
      primary in vivo responses, and D-galactosamine-sensitized mice succumbed to
      lethal shock. Polymerase chain reaction analyses revealed that CD4+V beta 8+
      expressed IL-2-specific mRNA in vivo upon restimulation with SEB. While
      lymphokine production and expression of the IL-2 receptor was similar to the
      response to in vivo primary stimulation, only CD8+V beta 8+ T cells expanded
      clonally upon reintroduction of SEB in vivo. Hence primed V beta 8+ T cells
      challenged with SEB display in vitro anergy yet in vivo responsiveness, at least
      in part. We conclude that the state of anergy is reversible, dependent upon the
      quality of activation signals provided in in vivo rather than in in vitro culture
      conditions.

PMID- 7718508
TI  - Sharing of the IL-2 receptor gamma chain with the functional IL-9 receptor
      complex.
AB  - The third subunit, the so-called common gamma (gamma c) chain, of the IL-2
      receptor is shared among the receptors for IL-2, IL-4, IL-7 and IL-15, and
      dysfunction of the gamma c chain is thought to cause X-linked severe combined
      immunodeficiency (XSCID) ascribed to impairment of early T cell development.
      However, cytokines linked to XSCID are as yet unidentified. A mAb specific for
      the gamma c chain, TUGm2, profoundly inhibited cell proliferation in response to
      IL-9. Another mAb, TUGm3, immunoprecipitated [125I]IL-9 cross-linked with either
      the IL-9 receptor or the gamma c chain. These results demonstrate that the gamma
      c chain is included in the functional receptor complex for IL-9, which was
      initially characterized as a T cell growth factor and is essential for IL-9
      dependent growth signal transduction.

PMID- 7718509
TI  - Modulation of specific T cell responses by concurrent infection with Leishmania
      major and LP-BM5 murine leukemia viruses.
AB  - C57BL/6 mice infected with a murine leukemia virus (MuLV) mixture designated LP
      BM5 develop an immunodeficiency syndrome termed MAIDS, characterized by a variety
      of T and B cell abnormalities, including elevated levels of IgE, suggesting that
      IL-4 expression is increased in these animals. It has been suggested that the
      immunodeficiency associated with MAIDS is caused by a conversion of immune
      responses normally characterized by Th1 development towards a Th2-dominated
      response. Mice of the same strain, infected with Leishmania major, mount a
      protective Th1 response with the induction of high levels of IFN-gamma and
      undetectable IL-4. We therefore infected mice with L. major at differing time
      points before and after virus infection and assessed the effects on T cell
      responsiveness, cytokine production and survival to L. major, as well as the
      effect on MAIDS-associated pathology. We have also immunized C57BL/6 mice with
      trinitrophenol-keyhole limpet haemocyanin (TNP-KLH), which leads to a
      predominantly Th2 response, and compared the effects of MAIDS on the response to
      TNP-KLH with the effect of MAIDS on L. major infection. Our results show that
      significant immunodeficiency with regard to infection by L. major is only
      apparent after 8 weeks of LP-BM5 MuLV infection, by which time T and B cell
      defects are well advanced. Further, we have found that the strongly polarized Th1
      response stimulated by L. major infection can modulate the effect of MAIDS on T
      cells, leading to the survival of antigen-specific T cells. Our results suggest
      that the impairment of immune responses to either TNP-KLH or L. major is due not
      to an alteration of the balance of Th1/Th2 subsets but to a general loss of
      reactivity in antigen-specific CD4+ cells. However, prior activation of Th1 but
      not Th2 cells can inhibit the development of lymphoproliferation and
      immunodeficiency caused by MAIDS.

PMID- 7718510
TI  - Molecular analysis of TCR junctional variability in individual infiltrated islets
      of non-obese diabetic mice: evidence for the constitution of largely autonomous T
      cell foci within the same pancreas.
AB  - Insulitis develops in non-obese diabetic (NOD) mice as a multicentric and
      asynchronous process. In an effort to understand how this T cell mediated process
      expands within each islet and propagates between the islets of the same pancreas,
      we have analyzed the junctional diversity of TCR V beta 6 and V beta 8.2
      transcripts cloned from infiltrated islets. The material examined was obtained
      from individual islets of 8 and 12 week old NOD mice or from pooled islets of 4
      week old individual mice. Compared with spleen transcripts, where every V beta 6
      or V beta 8.2 clone displays a different junction, islet transcripts are
      considerably less diverse. Each islet harbors from one to a maximum of six
      independent CDR3 sequences out of 10 or more analyzed colonies. On the other
      hand, there is an overall diversity of sequences when comparing the islets of the
      same pancreas or individual mice at 4 weeks. Altogether, these results support
      the idea that TCR repertoires are already divergent at the very early onset of
      insulitis and that each islet-centered infiltrate develops rather autonomously
      from the oligoclonal expansion of a limited set of precursors. Recirculation
      between islets is limited and does not seem to be the main mode of propagation of
      insulitis. Finally, a close analysis of J beta usage and N additions in beta
      chain transcripts from infiltrating cells reveals definite biases suggestive of
      an ongoing selective process imposed upon intra-pancreatic T lymphocytes.

PMID- 7718512
TI  - Defective IL-5-receptor-mediated signaling in B cells of X-linked immunodeficient
      mice.
AB  - Murine (m) IL-5 induces proliferation and differentiation of both Ly-1+ B cells
      and activated conventional B cells. X-linked immunodeficient (XID) mice do not
      respond to thymus-independent type II antigens, and have an abnormal response to
      a variety of activation signals through Ig receptors, CD40 and cytokine
      receptors. Furthermore, XID mice show a B cell specific defect, reflected in
      decreased numbers of IL-5R alpha+ B cells and reduced responsiveness of IL-5R
      alpha+ B cells to mIL-5. We generated IL-5R alpha transgenic (5R alpha-Tg) mice
      in which B cells expressed recombinant IL-5R alpha. We crossed male 5R alpha-Tg
      mice with female XID mice and used their offspring to determine the IL-5
      responsiveness of these B cells. All B cells of F1 male mice carrying the xid
      gene together with the transgene expressed the recombinant IL-5R alpha. However,
      those mice lacked Ly-1 B cells and their B cells acquired responsiveness to mIL
      5. Interestingly, XID-5R alpha-Tg B cells, but not XID B cells, acquired mIL-5
      proliferative and Ig-secretory responsiveness only in the presence of suboptimal
      doses of lipopolysaccharide. Stimulation of these B cells with mIL-5 plus phorbol
      myristate acetate induced proliferation, but not Ig secretion. These results
      indicate that the impaired mIL-5 responsiveness of B cells in XID mice is due to
      an abnormality of IL-5R-mediated signaling which may correlate with the xid gene
      mutation, alteration of a single amino acid of Bruton's tyrosine kinase.

PMID- 7718511
TI  - Immunization with the malaria heat shock like protein hsp70-1 enhances
      transmission to the mosquito.
AB  - Mosquitoes fed on mice infected with Plasmodium yoelii after an immunization with
      the i72 recombinant form of the heat shock protein hsp70-1 developed
      significantly more oocysts than mosquitoes fed on controls. This effect was due
      to a marked increase in the relative numbers of gametocytes during the early
      stages of infection. A comparison of blood-induced and sporozoite-initiated
      infection showed that these gametocytes were derived from merozoites released
      from the liver. The stimulus for increased gametocyte production is unknown but
      is likely to be linked with antibody-dependent cellular cytotoxicity and
      associated cytokine responses.

PMID- 7718513
TI  - Production of IgG autoantibodies to TCRs in mice infected with the retrovirus LP
      BM5.
AB  - Autoantibodies (AAbs) directed against particular segments of the variable region
      of TCR beta chains occur in normal humans and in certain autoimmune diseases, but
      the factors regulating the appearance of such antibodies are unknown. We report
      that AAbs binding a peptide determinant corresponding to the CDR1 of the V beta
      domain are elevated in C57BL/6 mice following infection with the LP-BM5 murine
      leukemia retrovirus mixture, a treatment used to induce murine AIDS. The
      elevation of the level of these AAbs is an early event following retroviral
      infection which corresponds in part to the general polyclonal activation of the B
      cells, but a selectivity for particular V beta sequences is apparent later. This
      suggests that the appearance of these antibodies may play a part in the
      subsequent development of immunodeficiency. Since the antibodies studied are of
      the IgG isotype, both T cells and B cells are involved in their elaboration.

PMID- 7718514
TI  - Impaired CD28-mediated co-stimulation in anergic T cells.
AB  - We have investigated a CD28 co-stimulation in anergic T cells in staphylococcal
      enterotoxin B-inoculated mice by stimulating the cells with a plate-coated anti
      TCR antibody in the presence or absence of an anti-CD28 antibody. CD28 co
      stimulation increased the levels of IL-2 and IL-4 mRNAs in naive CD4+V beta 8+ T
      cells. However, it did not increase the levels of IL-4 mRNA at all and only
      partially increased those of IL-2 mRNA in anergic T cells. It was demonstrated
      that CD28 co-stimulation was impaired so that it no longer stabilized cytokine
      mRNAs in anergic cells. The levels of IL-4 mRNA in response to TCR stimulation
      were higher in anergic T cells than those in naive T cells in spite of the
      defective CD28 co-stimulation in the former cells. Anergy induction and
      generation of a Th2-type immune response in vivo are discussed.

PMID- 7718515
TI  - In vivo induction of CD4+ T cell responses by antigens covalently linked to
      synthetic microspheres does not require adjuvant.
AB  - Macrophages, dendritic cells or B lymphocytes have been shown to play a major
      role in the presentation of soluble antigens to CD4+ T cells. In contrast, the
      capacity of these cells to present particulate antigens such as bacterial or
      parasitic antigens to T cells remains controversial. To investigate this
      question, well defined particulate antigens were prepared by covalent linkage of
      proteins or peptides to 1 micron in diameter synthetic microspheres. The T cell
      immunogenicity of such particulate antigens was analyzed in vitro and in vivo. In
      vitro, a soluble protein such as hen egg lysozyme (HEL) coupled to beads
      stimulated a strong proliferative T cell response of lymph node cells from HEL
      primed mice or of specific T cell hybridomas. HEL coupled to beads was presented
      to the specific T cell hybridomas by splenocytes or by peritoneal macrophages,
      but not by lymphoma B cells. Immunization of mice with several different protein
      antigens or with a synthetic peptide covalently linked to beads induced strong
      CD4+ T cell responses in the absence of adjuvant. The strong in vivo
      immunogenicity of proteins coupled to beads did not result from a non-specific
      adjuvant effect of beads since covalent linkage of the antigen to beads was
      strictly required to induce T cell responses in the absence of adjuvant. In vivo
      treatment by carrageenan showed that macrophages are required for the in vivo
      stimulation of T cell responses by these particulate antigens. Thus, these
      results demonstrated the role of phagocytic cells, especially macrophages, for in
      vivo presentation of particulate antigens. These particulate antigens represent
      an interesting approach for the development of new vaccines, and for the in vivo
      analysis of the role of various antigen presenting cells in T cell activation and
      differentiation.

PMID- 7718516
TI  - Cross-linking of the CAMPATH-1 antigen (CD52) triggers activation of normal human
      T lymphocytes.
AB  - The CAMPATH-1 (CD52) antigen is a 21-28 kDa glycopeptide which is highly
      expressed on lymphocytes and macrophages and is coupled to the membrane by a
      glycosylphosphatidylinositol (GPI) anchoring structure. The function of this
      molecule is unknown. However, it is an extremely good target for complement
      mediated attack and antibody-mediated cellular cytotoxicity. The humanized
      CAMPATH-1H antibody, which is directed against CD52, is very efficient at
      mediating lymphocyte depletion in vivo, and is currently being used in clinical
      trials for lymphoid malignancy and rheumatoid arthritis. It is therefore
      important to examine the functional effects of this antibody on different
      lymphocyte sub-populations. Because several other GPI-linked molecules expressed
      on the surface of T lymphocytes are capable of signal transduction resulting in
      cell proliferation, we have investigated whether the CAMPATH-1 antigen can also
      mediate these effects. In the presence of phorbol esters and cross-linking anti
      Ig antibodies, mAbs specific for CD52 induced proliferation and lymphokine
      production in highly purified resting CD4+ and CD8+ T lymphocytes. The rat IgG2c
      YTH 361.10 anti-CD52 antibody, however, was able to activate resting CD4+ and
      CD8+ T cells directly without cross-linking or phorbol myristate acetate in the
      absence of Fc-bearing cells. Anti-CD52 antibodies also augmented the anti-CD3
      mediated proliferative response of CD4+ and CD8+ T cells when the two antibodies
      were co-immobilized onto the same surface or cross-linked in solution by the same
      second antibody. Both CD4+ CD45RA and CD4+ CD45RO T cells were stimulated to
      proliferate by anti-CD52 antibodies in the presence of appropriate co-stimulatory
      factors. Anti-CD52 mAbs did not, however, synergize with anti-CD2 or CD28 mAb to
      induce CD4+ T cell proliferation. The activation of CD4+ T cells by anti-CD52
      antibodies was inhibited by cyclosporin A, suggesting a role for the calcineurin
      dependent signal transduction pathways. Although CD52 could transduce a signal in
      T cells, anti-CD52 antibodies did not inhibit antigen-specific or polyclonal T
      cell responses, suggesting this molecule does not play an essential co
      stimulatory role in normal T cell activation.

PMID- 7718517
TI  - Differential patterns of production of granulocyte macrophage colony stimulating
      factor, IL-2, IL-3 and IL-4 by cultured islets of Langerhans from non-obese
      diabetic and non-diabetic strains of mice.
AB  - A Terasaki plate microculture system was developed to examine cytokine secretion
      by cultured islets of Langerhans from non-obese diabetic (NOD) and non-diabetic
      strains of mice. NOD islets were also scored for the degree of infiltrating
      mononuclear cell release after overnight culture to see if this correlated with
      cytokine levels. Each of the cytokines studied, i.e. granulocyte-monocyte colony
      stimulating factor (GM-CSF), IL-2, IL-3 and IL-4, showed different patterns of
      production. For NOD islets, GM-CSF and IL-3 levels correlated with the degree of
      infiltrate release, although production was not confined to islets that released
      mononuclear cells in vitro. However, GM-CSF differed from IL-3 in that it was
      produced by islets from some non-diabetic strains of mice, whereas IL-3
      production was confined to NOD islets. Surprisingly little IL-2 could be detected
      in NOD islet supernatants and message for IL-2 was not detected by reverse
      transcription polymerase chain reaction. Finally, male NOD islets produced more
      IL-4 than females, possibly related to the lower incidence of diabetes in males,
      but unlike GM-CSF and IL-3, IL-4 production did not correlate with the degree of
      infiltrate released in culture. Overall the results show a complicated pattern of
      cytokine production that may be associated with destructive or protective
      responses. This was particularly illustrated by the fact that islet production of
      all cytokines temporarily ceased in male NOD mice between 6 and 10 weeks of age,
      a phenomenon not seen in females.

PMID- 7718518
TI  - Regulated activity of the IgH intron enhancer (E mu) in the T lymphocyte lineage.
AB  - The activity of the IgH (E mu) enhancer in the T lymphocyte lineage has been
      investigated using both transgenic mice and transfection studies. Thymocyte
      fractionation experiments indicate that a transgene consisting of the bacterial
      chloramphenicol acetyl transferase (CAT) gene, linked to E mu and the SV40 early
      promoter (E mu-CAT), is expressed only in thymocytes with a mature medullary
      phenotype and not in immature cells. Transfection of this same construct into two
      thymoma cell lines representing different stages of thymocyte development mimics
      the pattern of activity observed in vivo. Further transfection experiments
      suggest that this pattern of expression might be attributed to the differential
      activity of the E2E3 and octanucleotide motifs of E mu during development. In
      contrast, an Ig lambda transgene (linked to E mu and an Ig V lambda promoter) is
      expressed in the majority of thymocytes. We envisage that the different patterns
      of expression of the two transgenes reflect interactions between their respective
      promoters and the factors which are bound to E mu at different stages of
      thymocyte development. Although differing in their pattern of expression within
      the thymus, the two transgenes share the property of extinction in peripheral T
      lymphocytes. These results indicate that the expression of E mu-linked transgenes
      in the thymus cannot simply be explained by activation of the enhancer in a
      lymphoid progenitor cell prior to B/T lineage divergence. Rather, the enhancer
      (or components of it) must be independently activated (and inactivated) during T
      lymphocyte development. Furthermore, this activity is consistent with the
      developmental timing of Ig DH-JH rearrangements in these cells.

PMID- 7718520
TI  - The role of thymus in the aging of Th cell subpopulations and age-associated
      alteration of cytokine production by these cells.
AB  - Mouse CD4+ T cells were subdivided into two subpopulations, naive (CD44low
      CD45RBhigh) and memory (CD44high CD45RBlow) T cells, by flow cytometric analysis.
      Examination of spleen and peripheral blood of C57BL/6 mice of various ages
      revealed that there was a reciprocal age-associated change in these two
      subpopulations, i.e. naive T cells predominant in young mice decreased with age,
      while memory T cells increased. In order to investigate the role of the thymus in
      the age change of naive and memory T cells, we employed two experimental systems:
      radiation bone marrow chimeras constructed between young and old mice, and
      grafting of young or old thymus into nude mice. Data from these two experiments
      suggested that the young thymus has a greater ability to provide naive T cells
      than the old thymus, while the old thymus favors the maintenance of memory T
      cells rather than naive T cells. In reference to cytokine production by enriched
      naive and memory T cells, young naive T cells produced mainly IL-2 and young
      memory T cells mainly IL-4. On the other hand, in old mice, memory T cells
      produced twice as much IL-2 than naive T cells, although the level was
      significantly lower than that of young mice. In addition, old naive T cells
      produced twice as much IL-4 than old memory T cells. These results suggested a
      distinct age change in the profile of cytokine production and functional
      heterogeneity of two Th cell subpopulations.

PMID- 7718521
TI  - Academic responsibility for research.

PMID- 7718519
TI  - IL-1 receptor and TCR signals synergize to activate NF-kappa B-mediated gene
      transcription.
AB  - Previous studies have demonstrated that IL-1 receptor (IL-1R)- and TCR-initiated
      signals can interact synergistically to increase the rate of transcription of
      several lymphokine and lymphokine receptor genes during the competence phase of
      the activation program in T helper lymphocytes. In this report we describe how
      signals initiated through the type I IL-1R interact with signals from the antigen
      receptor to synergistically augment the transactivating properties of NF-kappa B.
      The synergistic antigen receptor initiated signals are mediated through protein
      kinase C because they can be mimicked by the phorbol ester, 12-O
      tetradecanoylphorbol-13-acetate, but not with calcium ionophores; and are
      staurosporine sensitive but cyclosporine resistant. Gel shift analyses
      demonstrate that NF-kappa B nuclear translocation is stimulated primarily by IL-1
      rather than by antigen receptor signals. Western blot and phosphorylation
      analyses demonstrate that the synergistic effect on NF-kappa B functional
      activity is independent of I kappa B alpha (MAD3)-NF-kappa B dissociation in the
      cytosol and is not associated with I kappa B nuclear translocation. The IL-1
      induced NF-kappa B DNA nuclear localization is transient and can be prolonged
      either by an antigen receptor-initiated signal or by inhibiting protein
      synthesis. These results suggest that IL-1 induces both NF-kappa B nuclear
      translocation and the synthesis of a protein(s) responsible for terminating NF
      kappa B-DNA interaction in the nucleus. Antigen receptor signals prolong NF-kappa
      B-DNA interaction, probably by functionally antagonizing the IL-1-induced
      synthesis of a protein(s) responsible for the transient NF-kappa B-DNA
      interaction and consequently synergistically enhance IL-1-induced NF-kappa B
      dependent gene transcription.

PMID- 7718522
TI  - Acceptance and perception of percutaneous endoscopic gastrostomy by patients with
      upper aerodigestive tract cancer.
AB  - Surgeons have identified a role for percutaneous endoscopic gastrostomy (PEG) in
      selected patients with upper aerodigestive tract cancer, but little is known
      about the patient's acceptance and perception of PEG. Nineteen patients with
      upper aerodigestive tract cancer had placement of a PEG and were asked about
      their perceptions via a series of descriptors and associated questions. The 13
      patients who had PEG placement under local anaesthesia and intravenous midazolam
      were questioned 12-16 h later and reported that the procedure was comfortable and
      not as bad as expected. These patients together with a further 6 patients who had
      placement under general anaesthesia were questioned about their acceptance of the
      PEG tube after 10 days. Comfort, ease of use and maintenance, and coverage by
      clothing confirms that PEG is an acceptable delivery system for enteral nutrition
      in patients with upper aerodigestive tract cancer.

PMID- 7718523
TI  - Temporomandibular joint arthrocentesis and lavage for the treatment of closed
      lock: a follow-up study.
AB  - OBJECTIVES: Temporomandibular joint (TMJ) arthrocentesis and lavage, first
      described in the North American literature in 1991, is a simplified method used
      for the treatment of severe, limited mouth opening. The purpose of this study is
      to evaluate the efficacy of this technique as a treatment for closed lock of the
      TMJ. DESIGN: Forty-six patients with persistent closed lock of the TMJ of acute
      onset were treated by TMJ arthrocentesis and lavage with manipulation in an out
      patient setting. Clinical data was collected in the form of visual analogue
      scales for pain and chewing ability, and measurements of maximum mandibular
      opening before and after treatment. RESULTS: On follow-up ranging from 6 to 30
      months, jaw opening and mandibular function had significantly improved (p <
      0.001), and pain had substantially decreased in all but one patient as a result
      of this procedure. CONCLUSION: TMJ arthrocentesis and lavage is recommended as a
      simple alternative to more invasive TMJ procedures as an effective technique for
      the treatment of acute persistent closed lock of the TMJ.

PMID- 7718524
TI  - Maxillary ameloblastoma: a retrospective study of 13 cases.
AB  - Ameloblastoma is uncommon in the maxilla, comprising about 15% of all reported
      ameloblastomas. Ameloblastomas are locally aggressive and, when involving the
      maxilla, potentially lethal. The long term outcome of 13 patients with
      ameloblastoma in the maxilla for whom surgery was the primary treatment between
      1951-1990 was studied. Patient records from both private and public practices in
      Melbourne, Australia were examined as were those cases reported to the Bone
      Tumour Registry at the University of Bristol, England. The study showed that
      control of disease was achieved in all patients where the tumour was limited to
      the confines of the maxilla (10 cases). The mean follow-up period in this group
      was 7 years (range 2-20 years). In the three cases that recurred all had
      preoperative radiological evidence of posterior maxillary sinus wall destruction
      and/or pterygoid plate erosion. Two patients died of extensive local recurrence
      and one has persistence of the disease. Histopathological examination confirmed
      the diagnosis of ameloblastoma in each case with a variety of histological
      patterns being noted. It is concluded that notwithstanding histological type, the
      extent of the tumour at presentation and the adequacy of the surgical approach
      and removal were the main factors in successfully managing the disease.

PMID- 7718525
TI  - Evolving role of modifications in neck dissection for oral squamous carcinoma.

PMID- 7718526
TI  - Third molar surgery: an audit of the indications for surgery, post-operative
      complaints and patient satisfaction.
AB  - A prospective investigation was undertaken of 522 patients undergoing third molar
      surgery. Data relating to indications for surgery and quality of care were
      collected on both pre- and post-operative proformas. This investigation showed
      that over half of the patients did not have clinically sound indications for
      surgery. The incidence of post-operative complications was approximately the same
      as other studies on third molar surgery. Patient satisfaction was at a high
      level, although this study revealed that a percentage of symptom-free patients
      undergoing third molar surgery sustained nerve damage some of which remains
      unreported. Clear and well defined indications for third molar surgery do exist
      and should be adhered to. Operating on patients without good reason involves
      unnecessary expenditure to purchasing authorities, cost to the patient in both
      time off work and post-operative complications and further, may result in
      potentially avoidable legal problems for practitioners. A reappraisal of the
      impacted third molar is indicated prior to committing the patient to surgery,
      such that the indications for surgery are compatible with current views on
      quality assurance, health service economics and medico-legal common sense.

PMID- 7718528
TI  - Morphometric analysis of orbital, buccal and subcutaneous fats: their potential
      in the treatment of enophthalmos.
AB  - Retro-orbital fat volume reduction has been reported in patients with
      enophthalmos but could be restored by a suitable fat autograft. Buccal and
      subcutaneous adipose tissues were identified as possible donor sites. Samples of
      these and of orbital fat were obtained from fresh cadavers, and the relative
      volumes of collagen and of endothelial cells and the numerical density of mast
      cells were compared since these might influence graft survival. The results
      demonstrated strong similarities between orbital and buccal fat which were
      significantly different from subcutaneous fat. It was concluded that the buccal
      fat pad would be a more suitable donor site than subcutaneous adipose tissue to
      replace orbital fat loss and that its use merits further investigation.

PMID- 7718527
TI  - Open-packing method for the severely comminuted fractured mandible due to missile
      injury.
AB  - A new approach is introduced to treat a severely comminuted fractured mandible
      due to missile injury, whereby denuded bony pieces are re-incorporated into the
      defect. These are then immobilized by open-packing with iodoform ribbon gauze.
      The pack is changed regularly every 10-14 days until the cavity is completely
      obliterated with healthy granulation tissue by which time the mandible shows good
      consolidation with re-alignment of all displaced bony fragments. The method is
      simple, safe, does not need an expert surgeon and avoids the need for a future
      bone graft. Iodoform packs were used in different sites of the facial skeleton
      and none of our patients showed signs of sensitivity to iodoform or to iodine
      toxicity.

PMID- 7718529
TI  - Central giant cell granuloma of jaws--review of 19 cases.
AB  - 19 cases of central giant cell granuloma (CGCG) were reviewed after screening the
      records of the past four years of the Dental out patient department of AIIMS
      Hospital, New Delhi. It was found that CGCG usually occurs in the 2nd and 3rd
      decades and is more common in females. The mandible is more frequently involved
      than the maxilla and lesions occur more commonly on the right than left side.

PMID- 7718530
TI  - Malignant ameloblastoma revisited.
AB  - A case of a malignant ameloblastoma in a 49-year old Sri Lankan woman with
      widespread pulmonary metastases is presented, the diagnosis confirmed by needle
      biopsy. The current histological classification of odontogenic carcinomas and the
      management of metastatic pulmonary deposits are discussed.

PMID- 7718532
TI  - Head and neck stabbing injuries.

PMID- 7718531
TI  - Cleft malformation of lip, alveolus, hard and soft palate, and nose (LAHSN)--a
      critical view of the terminology, the diagnosis and gradation as a basis for
      documentation and therapy.
AB  - The hope for the improvement of the treatment of patients with a cleft
      malformation of lip, alveolus, hard and soft palate, and nose (LAHSN) is to
      review and to compare new concepts and methods. But research in this way presumes
      an exact, reliable and reproduceable diagnosis and documentation. This article
      reviews previously published diagnosis and documentation systems, and also
      suggests a concise and simple system to record a cleft lip and palate diagnosis.
      The anatomical regions of the cleft are considered as well as their extent. A
      three way division to record the extent of the malformed regions is proposed. It
      is a extensively used diagnosis recording system.

PMID- 7718533
TI  - An update on the careers of dentists undertaking a medical qualification.

PMID- 7718534
TI  - Shaving the temporal hair.

PMID- 7718535
TI  - Orthognathic surgery: patient expectations; psychological profile and
      satisfaction with outcome.
AB  - 61 orthognathic surgery patients were studied (39% male, 61% female). It confirms
      that the group of patients we see in the West of Scotland are well adjusted
      psychologically and that the majority seek orthognathic surgery for aesthetic
      reasons. The degree of satisfaction is high (87%). Dissatisfaction is not related
      to sex, age or procedure. Patients who were dissatisfied tend to have higher
      neuroticism scores on the Eysenck Personality Inventory and those patients who
      had had unreal expectations of post surgical pain, numbness and swelling, were
      likely to express dissatisfaction with the outcome in the early stages. Several
      patients initially expressed some dissatisfaction with the outcome after 3 months
      then went on to increase their score and by 12 months became satisfied with the
      procedure. The authors outline the importance of adequate patient preparation
      prior to surgery and the use of printed literature is recommended.

PMID- 7718536
TI  - Nutrient bandwagons.

PMID- 7718537
TI  - The use of intragastric nutrition to study saliva secretion and the relationship
      between rumen osmotic pressure and water transport.
AB  - Four sheep sustained by intragastric nutrition were used to study saliva
      secretion and the relationship between osmotic pressure in the rumen and net
      water transport across the rumen wall. Different concentrations of buffer were
      infused into the rumen to change the rumen osmotic pressure. Salivary secretion
      was estimated from entrance of P into the rumen. Net water transport across the
      rumen wall was calculated as the difference between water inflow and water
      outflow from the rumen. A negative linear relationship between the rumen osmotic
      pressure (X, mOsm/kg) and the water absorption across the rumen wall (Y, ml/h)
      was found: Y = (394 SE 8.3)-(1.22 SE 0.03) X, r2 0.83, (P < 0.001), and a
      positive linear relationship was found between the rumen osmotic pressure (X,
      mOsm/kg) and the outflow rate of rumen fluid (Y, ml/h): Y = (34.0 SE 8.0) + (0.97
      SE 0.03) X, r2 0.56, (P < 0.001). The implication is that rumen osmotic pressure
      can be a key factor in the control of the net water transport across the rumen
      wall, the outflow of rumen fluid to omasum and the rumen liquid dilution rate. A
      method is suggested by which salivary secretion in sheep may be calculated from
      the water balance in the rumen.

PMID- 7718538
TI  - The influence of dietary advice on nutrient intake during pregnancy.
AB  - To assess the effect of an antenatal nutrition programme designed specifically
      for the local population, questionnaires on nutrition knowledge, attitudes to
      healthier eating and 4 d diet diaries were completed by women attending routine
      antenatal clinics. Women who received the nutrition education programme were
      allocated into an Intervention Education Group whilst those women who did not
      were allocated into a Routine Education Group. The results showed that knowledge
      about nutrition was significantly higher in the intervention group. However, no
      significant differences were detected between the two groups for attitude
      variables or nutrient intake. It is concluded, therefore, that the most-widely
      read form of nutrition advice for pregnant women may have some impact on
      nutrition knowledge but has little effect on nutrient intake during pregnancy.

PMID- 7718539
TI  - Adaptation to high-fat diets: effects on eating behaviour and plasma
      cholecystokinin.
AB  - Twelve male subjects took part in a study to investigate the effects of
      overfeeding a high-fat diet (19.17 MJ/d; 58% energy from fat) for 2 weeks on
      plasma cholecystokinin (CCK) levels, food intake, and subjective feelings of
      hunger and fullness. Before and after the diet, subjects completed a 2-week
      weighed dietary inventory, formal measurements of food intake from a pre-selected
      appetizing evening meal were carried out, and blood samples were taken after a
      standard breakfast for measurement of CCK. Hunger and fullness were rated on
      visual analogue scales before and after each of these meals and at evening meals
      during the diet period. Following the high-fat diet there was a small non
      significant increase in food intake from the pre-selected meal (6919 (SE 615) kJ
      v. 6405 (SE 540) kJ; P = 0.1) and a significant increase in the average daily
      food consumption measured from the diaries (10.25 (SE 0.49) MJ/d v. 9.59 (SE
      0.62) MJ/d; P = 0.05). Corresponding trends of increasing feelings of hunger and
      declining fullness also occurred over the study period. Plasma CCK responses to
      the standard breakfast were raised following the diet (1285 (SE 153) v. 897 (SE
      78) pM min; 3 h integrated CCK production post v. pre diet; P < 0.01) with the
      major differences observed at 90 and 120 min following the meal. These results
      suggest that the increase in food intake may be related to a down-regulation in
      putative CCK receptors responsible for food intake. Elevated CCK levels might
      suggest a corresponding down-regulation in CCK receptors responsible for feedback
      inhibition of CCK release.

PMID- 7718540
TI  - The voluntary feed intake of pigs given feeds based on wheat bran, dried citrus
      pulp and grass meal, in relation to measurements of feed bulk.
AB  - Two experiments were carried out to investigate the capacities of pigs for bulky
      feeds. In Expt 1 fifteen pigs were offered, from 12 to 25 kg live weight, ad lib.
      access to one of five feeds which were made by progressively diluting a high
      quality feed with wheat bran. Intake initially increased, and then declined, as
      the proportion of wheat bran was increased. The pigs became better able to
      accommodate to the more bulky feeds over time. In Expt 2 thirty-six pigs,
      initially of 12 kg live weight, were used. The feeds were the same high-quality
      basal feed as in Expt 1 and three others made almost entirely of either wheat
      bran, dried grass or dried citrus pulp, respectively. The equal-parts mixtures of
      each of these three bulky feeds with the basal feed were also made to give three
      series of feeds each comprising the basal, the mixture and the bulky feed. The
      three feeds in each series were given ad lib. to twelve pigs in a design of two
      replicated Latin squares with three time-periods. Within each series, and across
      periods, the intakes of the feeds that were limiting intake were directly
      proportional to live weight and so a scaled intake, expressed as g/kg live weight
      per d, was calculated. Across the six limiting feeds, scaled intakes in the final
      5 d of each period, when the pigs were in equilibrium with their feeds, were
      directly proportional to the reciprocal of the water-holding capacities (WHC) of
      the feeds, as measured by a centrifugation method. There were large effects of
      feed changes on intake, in the short term, with previous experience of a bulky
      feed leading to higher intakes of another bulky feed. The intake of the basal
      feed was not affected by the feed given previously. It was concluded that: (a)
      the time of adaptation to bulky feeds needs to be considered when attempting to
      measure, or predict, the rates of intake on different bulky feeds and, (b) the
      WHC of the feeds could be an appropriate measurement of 'bulk' responsible for
      limiting their intake, and could be used to predict the maximum feed intake
      capacity of pigs on different bulky feeds.

PMID- 7718541
TI  - Adaptation of energy metabolism to undernutrition in ewes. Contribution of portal
      drained viscera, liver and hindquarters.
AB  - Adaptation of energy metabolism to undernutrition and to the duration of
      undernutrition was studied in adult, non-pregnant, non-lactating ewes at the
      whole-animal, portal-drained viscera, liver and hindquarters levels. Arterio
      venous and indirect calorimetry techniques were used. Animals were successively
      fed at 1 times (3 weeks) and at 0.5 times (7 weeks) their metabolizable energy
      requirements for maintenance (MEm). Portal, hepatic and hindquarters blood flows
      in quietly standing ewes decreased by 22, 19 and 11% respectively within the
      first week of undernutrition and remained at that level thereafter. Standardizing
      hindquarters blood flow to that in a given posture (quietly standing) reduced
      blood flow by 9.8%. In the portal-drained viscera and liver, O2 extraction rates
      decreased, leading to 34 and 38% drops in O2 consumption with underfeeding
      respectively. In the hindquarters, O2 extraction rate increased, partly
      counterbalancing the drop in blood flow. Thus O2 consumption of hindquarters
      tended to decrease but the effect was not significant. All changes appeared to be
      completed from day 5 of underfeeding. Consequently, the portal-drained viscera,
      liver and carcass were responsible for 39, 32 and 5% respectively of the drop in
      whole-animal O2 consumption with underfeeding. At the end of the 0.5 x MEm
      period, in vivo metabolic rates averaged 1.65, 4.89 and 0.38 mmol O2 consumed/d
      per g fresh weight of adipose-tissue-free portal-drained viscera, liver and
      boneless hindquarters respectively. Undernutrition imposed a much greater
      nutritional challenge to splanchnic tissues than to hindquarters. The former
      reduced their energy expenditure whereas hindquarters metabolism adapted by
      counteracting the slight drop in nutrient supply.

PMID- 7718542
TI  - Metabolism of ornithine, alpha-ketoglutarate and arginine in isolated perfused
      rat liver.
AB  - Ornithine (Orn; alpha-ketoglutarate (alpha KG) salt) and arginine (Arg)
      supplementation of enteral diets has been advocated in the treatment of
      hypercatabolism of trauma patients, but both compounds are subject to extensive
      hepatic metabolism. To compare the metabolism of these two compounds and to
      evaluate the possible influence of the alpha KG moiety, livers were perfused with
      alpha KG, Orn, ornithine alpha-ketoglutarate (OKG) or Arg (n 6 in each group) for
      1 h. Arg uptake was nearly fourfold higher than Orn uptake (690 (SD 162) v. 178
      (SD 30) nmol/min per g liver), and Orn uptake was not modified by alpha KG. Orn
      was totally metabolized by the liver, whereas Arg led to Orn release (408 (SD
      159) nmol/min per g liver) and a threefold stimulation of urea production (Arg
      1.44 (SD 0.22) v. Orn 0.45 (SD 0.09) mumol/min per g liver). alpha KG alone only
      increased hepatic aspartate uptake but, when associated with Orn as OKG, it led
      to an increase in glutamate release and in proline content in the liver and to a
      decrease in proline uptake. From these findings we conclude that (1) Arg load is
      extensively metabolized by the liver, inducing urea production, (2) in enteral
      use, Orn supplementation appears preferable to Arg as it is less ureogenic (as
      also recently demonstrated in vivo in stressed rats receiving isomolar amounts of
      Arg and Orn), (3) the liver participates in the Orn-alpha KG metabolic
      interaction, mostly in proline metabolism, which occurs in the splanchnic area.

PMID- 7718543
TI  - Effects of dietary propionate on hepatic glucose production, whole-body glucose
      utilization, carbohydrate and lipid metabolism in normal rats.
AB  - Increased intake of dietary fibres is associated with several beneficial effects
      on carbohydrate and lipid metabolism. The colonic fermentation of dietary fibres
      produces short-chain fatty acids (SCFA; acetate, propionate and butyrate). Some
      authors have suggested that SCFA could be partly responsible for the effects of
      dietary fibres. The purpose of the present study was to test the effects of one
      of the SCFA, propionate. The effects of moderate amounts of dietary propionate on
      insulin sensitivity and hepatic glucose production were studied in male Sprague
      Dawley rats. Two groups of twenty-one adult rats were fed for 3 weeks on a diet
      containing 78 g propionate/kg (P) or 78 g/kg of a poorly fermentable cellulose
      (control group; C). Feed intake, body weight, fasting plasma glucose, insulin,
      free fatty acids, alanine, lactate, glycerol and beta-hydroxybutyrate levels were
      measured weekly in anaesthetized rats. At the end of the feeding period basal
      hepatic glucose production (BHGP) was measured with a primed continuous infusion
      of [3-3H]glucose and the in vivo insulin sensitivity in rats was quantified by
      the euglycaemic-hyperinsulinaemic clamp technique (0.6 and 2 U/kg per h). At that
      time fasting plasma glucose measured in anaesthetized rats was significantly
      lower in group P than in group C: 7.7 (SE 0.2) v. 8.5 (SE 0.2) mmol/l
      respectively (P < 0.002); plasma insulin levels were not significantly different.
      Neither the BHGP (mg/min per kg; C 14.8 (SE 1.3), P 15.1 (SE 1.3); n 7, not
      significant) nor the basal metabolic clearance (ml/min per kg; 8.9 (SE 0.8) v.
      9.9 (SE 1.1); not significant) were different between treatments. Hepatic glucose
      production and glucose utilization at the two insulin concentrations
      (approximately 500 and 1500 mU/l respectively, n 7) did not differ significantly
      between the two groups. These results show that dietary propionate chronically
      ingested by normal rats could decrease fasting glycaemia, but from our findings,
      no effect on hepatic glucose production and whole-body glucose utilization could
      be clearly demonstrated.

PMID- 7718544
TI  - Meal feeding and leucine utilization in pregnant rats.
AB  - During pregnancy a higher amino acid requirement may be expected, but the
      increase in food intake does not match the increased growth rate during
      pregnancy. It is hypothesized that amino acid utilization can be increased during
      both fasting and feeding in order to account for the increased requirement.
      Therefore mature female rats (20 weeks old) were investigated before and at day
      18 of pregnancy. Rats were fed on a high-protein (HP) diet (210 g casein/kg diet)
      for 3 weeks and fasted overnight. Rats were then subjected to an 8 h constant
      infusion of L-[1-14C]leucine with continuous measurement of expired 14CO2 (as a
      percentage of the infused dose). After 3 h infusion a 5 g HP or low-protein (LP;
      75 g casein/kg diet) meal was offered for 30 min. Pregnant rats had a
      significantly lower percentage leucine oxidation in the fasted state (12.5 (SE
      0.7) v. 15.9 (SE 1.1)%; P < 0.05), which suggests improved reutilization of
      leucine. Meal ingestion resulted in a fast increase in 14CO2 expiration. After
      the LP meal the level of 14CO2 expiration decreased again after the acute
      response (0-1.5 h), but this was not the case after the HP meal. After the HP
      meal (average 1.5-5 h), no difference was observed between pregnant and non
      pregnant status (36.8 (SE 1.6) v. 35.0 (SE 2.5)%). After the LP meal (average 1.5
      5 h), however, the percentage leucine oxidation tended to be lower in pregnant
      rats but this difference did not reach statistical significance (19.7 (SE 1.1) v.
      25.8 (SE 2.8)%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718545
TI  - The effect of heat on amino acids for growing pigs. 4. Nitrogen balance and
      urine, serum and plasma composition of growing pigs fed on raw or heat-treated
      field peas (Pisum sativum).
AB  - Experiments were conducted to determine the effect of heating field peas (Pisum
      sativum) on the N balance and urine, serum and plasma composition of growing
      pigs. In the first experiment, four diets containing raw field peas (cv. Wirrega)
      or field peas heated to 150 degrees (cv. Wirrega), 165 degrees (cv. Wirrega) or
      150 degrees (cv. Dundale) for 15 min respectively were formulated to contain 1.15
      g ileal digestible N/MJ digestible energy (DE) and 0.36 g ileal digestible
      lysine/MJ DE in a sugar-based diet. Digestibility estimates were based on those
      for the Dundale cultivar of field peas used in previous experiments. Total urine
      and faeces collection from eight pigs was conducted over two 7 d collection
      periods with a 7 d diet change-over period. Serial blood sampling from the
      external jugular vein was conducted on the final day of each collection period.
      There was no significant difference (P > 0.05) in the N balance or apparent
      biological value of the field-pea treatments. Pigs fed on diets containing peas
      heated to 150 degrees (cv. Wirrega) or 165 degrees (cv. Wirrega) had a
      significantly lower (P < 0.01) daily output of urea and uric acid in the urine,
      and depressed serum protein and serum urea concentrations. Plasma lysine
      concentration and daily urine lysine output were not significantly different (P >
      0.05) in pigs fed on heated peas. Protein excretion in the urine of pigs fed on
      diets containing peas heated to 165 degrees increased 3-7 times (depending on
      estimation technique) the level observed in pigs fed on diets containing raw
      peas. A second experiment was conducted to determine the apparent ileal
      digestibility of N and amino acids in cv. Wirrega field peas. This study revealed
      that N digestibility (0.44) and lysine digestibility (0.35) in peas heated to 165
      degrees were significantly lower than the cv. Dundale estimates (0.57 and 0.62
      respectively) used in diet formulations. The depressed serum and urine variables
      in pigs fed on heated peas were attributed to overestimation of digestibility.
      The results exemplify the fact that it is not possible to draw general
      conclusions as to the effects of heat on any particular protein concentrate.
      Variability in N balance experiments and problems associated with urine analysis
      are suggested as likely reasons for the current study not reflecting poor
      utilization of ileal digestible lysine from heat-treated field peas.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7718546
TI  - Effect of oat saponins on plasma and liver lipids in gerbils (Meriones
      unguiculatus) and rats.
AB  - The effects of oat saponins (a mixture of avenacosides A and B) on plasma and
      liver lipids in gerbils (Meriones unguiculatus) and rats were investigated.
      Cholesterol-containing diets high in total and saturated fat and with different
      avenacoside contents (zero (ethanol-extracted oats), normal (oats) and twice
      normal (ethanol-extracted oats plus added avenacosides)) were used. Compared with
      a cellulose control group the oat diets in both species gave a significantly
      higher cholesterol content in the HDL fraction and a significantly lower liver
      cholesterol content. No significant differences in total plasma cholesterol, HDL
      cholesterol and plasma triacylglycerols were found, however, between the groups
      fed on oats with different avenacoside content. The liver weight, total liver
      cholesterol and free liver cholesterol were also similar, whereas the liver lipid
      content was significantly lower in rats given the highest amount of avenacosides
      compared with zero or normal amounts. The tendency was the same in gerbils. Thus,
      the oat saponins had only minor effects on lipid metabolism in gerbils and rats.

PMID- 7718547
TI  - Both raw and retrograded starch decrease serum triacylglycerol concentration and
      fat accretion in the rat.
AB  - Male Wistar rats were meal-fed on diets containing various amounts of resistant
      starch in the form of raw starch (either amylomaize starch, potato starch or
      modified high-amylose starch) or retrograded starch (prepared from each of the
      starches) for 6 weeks. Two diets containing normal maize starch were fed as diets
      poor in resistant starch. Energy absorption (energy consumption minus faecal
      energy loss), growth, weight of the epididymal fat pads, serum total cholesterol
      and triacylglycerol concentrations and a number of intestinal and faecal
      variables were determined. The resistant starches affected all the variables
      determined except the serum total cholesterol concentration. Relationships were
      found between energy absorption and both growth and the weight of the fat pads,
      and between the weight of the fat pads and both the serum triacylglycerol
      concentration and the serum total cholesterol concentration. No clear differences
      between the effects of the two types of resistant starch (raw starch v.
      retrograded starch) were found except that raw potato starch hardly stimulated H2
      excretion and led to lower amounts of propionic and butyric acids in the caecal
      contents than the other starches. The results suggest that dietary resistant
      starch reduces energy absorption leading to less abdominal depot fat and lower
      serum triacylglycerol concentrations.

PMID- 7718548
TI  - Trace lipid from whey-mineral complex enhances calcium availability in young
      ovariectomized rats.
AB  - The effects of the trace lipids (L1 and L2) extracted from two kinds of whey
      mineral complex on bone metabolism were studied in young ovariectomized (OVX)
      rats. The concentrations of oestradiol in the L1 and L2 oils were 305 and 1313
      pg/ml respectively, while the concentrations of progesterone were 34.3 and 36.9
      ng/ml respectively. Trace amounts of 1 alpha,25-dihydroxycholecalciferol (1
      alpha,25-(OH)2D) were detected: 56 pg/ml in the L1 oil and 132 pg/ml in the L2
      oil. The OVX rats were orally given 0.4 ml each test oil twice weekly. Other
      animals were given with only a vehicle (control) or an oil mixture with similar
      levels of oestradiol and progesterone to those in L2 oil (PE oil) for comparison.
      The Ca absorption rate, bone density of the humerus and femoral Ca content in the
      rats given L2 were significantly higher than those in the control rats (P <
      0.05). Serum calcitonin and 1 alpha,25-(OH)2D from rats given L2 were both
      significantly higher than those from the control rats, while serum progesterone
      in the L2 group was slightly lower. It is suggested that the bone metabolism of
      rats given L2 reflected the compound effect of 1,25-(OH)2D and oestradiol in the
      L2 oil. In contrast, the relatively low level of these hormones might have been
      associated with the mediocre bone characteristics of the L1 group. It is
      suggested from these results that the trace level of hormones could be one of the
      reasons why whey-mineral complex showed good Ca availability.

PMID- 7718549
TI  - Effects of double-blind controlled calcium supplementation on calcium absorption
      in Chinese children measured with stable isotopes (42Ca and 44Ca).
AB  - A double-blind controlled Ca supplementation trial was conducted for 6 months in
      thirty-four 7-year-old Chinese children from Hongkong and Jiangmen, China. The
      children were randomly allocated to the study group (n 17) or control group (n
      17), and a CaCO3 tablet (300 mg Ca) or a placebo tablet was taken daily. True
      fractional Ca absorption (TFCA) was evaluated before and after the trial using
      stable isotopes: 8 mg 44Ca mixed in 100 g chocolate milk was given after an
      intravenous injection of 0.75 mg 42Ca. There was no significant difference in
      baseline TFCA between the study group (60.6 (SD 11.4)%) and the controls (58.2
      (SD 9.0)%; P = 0.55). Serum 25-hydroxycholecalciferol levels were comparable
      between the two groups (P = 0.71). After 6 months, TFCA of the study group (55.6
      (SD 12.7)%) was significantly lower than that of the controls (64.3 (SD 10.7)%; P
      = 0.015). By comparing the individual changes in TFCA after the trial between the
      two groups there was a non-significant reduction in TFCA (5.03 (SD 12.4)%; P =
      0.11, Wilcoxon signed-rank test) in the study group (60.6-55.6%), whereas a
      significant increase in TFCA (6.17 (SD 7.7)%; P = 0.004, Wilcoxon signed-rank
      test) was observed in the controls (58.2-64.3%). The differential in TFCA between
      the two groups after 6 months was significantly different (P = 0.001), and
      remained significant after adjustment for baseline dietary intakes, weight and
      height by multiple-regression analysis (P = 0.003). If the mechanism of TFCA from
      chocolate milk in response to the treatment effects is similar to that from the
      total diet, then our results suggest that children with adequate vitamin D status
      can adapt to a change in Ca intake by adjusting the efficiency of TFCA. In
      corollary, children on habitually-low Ca diets have a higher TFCA than the
      counterparts with higher Ca diets.

PMID- 7718551
TI  - Revisiting ground-state and transition-state effects, the split-site model, and
      the "fundamentalist position" of enzyme catalysis.
AB  - In 1978 Schowen laid out the "fundamentalist position" of enzyme catalysis:
      "...the entire and sole source of catalytic power is the stabilization of the
      transition state; reactant-state interactions are by nature inhibitory and only
      waste catalytic power." In 1992 Menger developed the "split-site model" in order
      to demonstrate contradictions of the fundamentalist position. One of Menger's
      examples is recounted in which the energy of the enzyme-substrate complex (delta
      GES) is lowered, yet the catalytic rate increases, incompatible with the claim
      that reactant- (i.e., ground-) state interactions are inhibitory. A rigorous
      definition of ground-state effect is proposed which resolves the apparent
      contradictions. A ground-state effect (delta delta GES) is defined as one in
      which the energy of the ground state has changed, but the energy of the catalyzed
      transition state is unchanged when one enzyme is compared to another. This is a
      result of the constraint that the free energy of binding of the enzyme to the
      uncatalyzed reaction transition state, delta Gb*, is constant. That ground-state
      interactions are inhibitory when a single enzyme-catalyzed reaction is considered
      has been proven by Schowen: this definition of ground-state effect achieves the
      result of making additional ground-state interactions inhibitory also. This
      definition is rather restrictive, however, and does not describe many of the
      possible changes in enzyme energy levels. A proposal is therefore put forth to
      simply explain the changes in terms of alterations in intrinsic and utilized
      binding energy.

PMID- 7718550
TI  - Energy intake and expenditure in elderly patients admitted to hospital with acute
      illness.
AB  - Studies on hospitalized elderly subjects have demonstrated that negative energy
      balance is common during hospitalization, but have concentrated primarily on long
      stay and psychogeriatric patients. There is little information on energy balance
      in elderly patients admitted with acute illness from the community, despite the
      importance of this patient group and the presence of a number of factors likely
      to predispose such patients to negative energy balance. In the present study
      energy balance was quantified in twenty patients (eight males, mean age 82 (SD 5)
      years; twelve females, mean age 84 (SD 6) years) admitted from the community with
      acute illness, and predicted basal metabolic rate (BMR) was compared with
      measured resting metabolic rate (RMR). Most patients were in negative energy
      balance during hospitalization, and median measured energy intake (EI): measured
      RMR ratio was 1.0 (range 0.7-1.8). The mean difference between measured EI and
      estimated total energy expenditure was -1.3 MJ/d (range -3.4 to +2.5 MJ/d).
      Estimated total energy expenditure exceeded measured EI in fifteen of the
      patients and there was a significant decline in mid-arm muscle circumference
      (paired t, P < 0.05) during hospitalization. We conclude that moderate negative
      energy balance is common in this patient group, and that these patients are at
      risk of undernutrition during their hospital stay.

PMID- 7718552
TI  - Structure of a third cooperativity state of hemoglobin: ultraviolet resonance
      Raman spectroscopy of cyanomethemoglobin ligation microstates.
AB  - Ultraviolet resonance Raman (UVRR) spectra have been obtained for cyanometHb (Hb
      = hemoglobin) hybrid tetramers representing several ligation microstates, using
      dimer interchange techniques and spectral subtraction. Relative to fully ligated
      tetramers, Hb(CN)4, the monoligated hybrids and deoxyHb all show fully developed
      T/R difference UVRR bands which are associated with T state quaternary contacts
      across the alpha 1 beta 2 interface, involving the Trp beta 37 and Tyr alpha 42
      residues. Triligated species show quite different signals, arising from the
      interior residues Trp alpha 14 and/or beta 15. From earlier studies, these Rdeoxy
      signals are attributed to E helix displacement toward the heme in deoxy subunits
      within R state tetramers, resulting in weakened Trp H-bonds. Asymmetric diligated
      hybrids, containing both ligands in the same dimer unit, show signals
      characteristic of the T quaternary contacts, but they are attenuated by 40%. An
      equilibrium mixture of T and R state molecules is ruled out by the absence of
      significantly strong Rdeoxy difference bands. Rather, the spectral attenuation is
      attributed to weakening of the T state contacts at the alpha 1 beta 2 interface.
      This interpretation is supported by previous observations that the mutational
      pattern of free energy perturbations for the asymmetric hybrid is T-like and not
      that of a T/R equilibrium or an R-like state. The asymmetric hybrid represents a
      third cooperativity state, T', having a T quaternary arrangement of the subunits
      but a deformed alpha 1 beta 2 interface, with weakened contacts.

PMID- 7718553
TI  - Transition-state selectivity for a single hydroxyl group during catalysis by
      cytidine deaminase.
AB  - Cytidine deaminase binds transition-state analog inhibitors approximately 10(7)
      times more tightly than corresponding 3,4-dihydro analogs containing a proton in
      place of the 4-hydroxyl group. X-ray crystal structures of complexes with the two
      matched inhibitors differ only near a "trapped" water molecule in the complex
      with the 3,4-dihydro analog, where contacts are substantially less favorable than
      those with the hydroxyl group of the transition-state analog. The hydrogen bond
      between the hydroxyl group and the Glu 104 carboxylate shortens in that complex,
      and may become a "low-barrier" hydrogen bond, since at the same time the bond
      between zinc and the Cys 132 thiolate ligand lengthens. These differences must
      therefore account for most of the differential binding affinity related to
      catalysis. Moreover, the trapped water molecule retains some of the binding
      energy stabilizing the hydroxyl group in the transition-state analog complex. To
      this extent, the ratio of binding affinities for the two compounds is smaller
      than the true contribution of the hydroxyl group, a conclusion with significant
      bearing on interpreting difference free energies derived from substituent effects
      arising from chemical modification and/or mutagenesis.

PMID- 7718554
TI  - Spectroscopic studies on the mechanism of the topa quinone generation in
      bacterial monoamine oxidase.
AB  - Electron paramagnetic resonance (EPR), circular dichroism (CD), and optical
      absorption spectroscopies have been used to investigate the copper-dependent
      autoxidation process generating the 6-hydroxydopa (topa) quinone cofactor in the
      recombinant phenethylamine oxidase from Arthrobacter globiformis. The cupric ion
      bound to the copper/topa quinone-less, inactive enzyme is first reduced to Cu(I),
      as inferred from the spectroscopic features observed under strictly anaerobic
      conditions. Cu(I) is also detectable chemically with a Cu(I)-specific chelating
      agent, bathocuproinedisulfonate. Introduction of a limited amount of oxygen then
      leads to the formation of a paramagnetic species (g = 2.004) that is stable for
      over several to 10 min but vanishes swiftly upon addition of sufficient oxygen.
      Strikingly, the hyperfine EPR structure of the organic radical is almost
      identical with that of the topa semiquinolamine observed in the copper/topa
      quinone-containing, active enzyme anaerobically reduced with substrate.
      Concomitant with the generation of topa quinone exhibiting characteristic optical
      absorption and CD bands under fully aerobic conditions, the bound copper finally
      shows EPR signals typical of nonblue type II Cu(II) and optical absorption around
      700 nm with negative CD above 700 nm. None of these spectral changes are evoked
      in the binding of Cu(II) to the Tyr382-->Phe mutant enzyme, indicating that the
      precursor Tyr382 to topa quinone participates in the initial reduction of bound
      copper and serves as the origin of the transiently formed semiquinone radical.
      The prosthetic cupric ion plays an essential role, by changing its redox state,
      in the oxidative modification of the tyrosyl phenol ring, leading to topa
      quinone.

PMID- 7718555
TI  - Mechanistic insights provided by deletion of a flexible loop at the active site
      of ribulose-1,5-bisphosphate carboxylase/oxygenase.
AB  - To evaluate the functions of flexible loop 6 at the active site of Rhodospirillum
      rubrum D-ribulose-1,5-bisphosphate carboxylase/oxygenase, the loop was truncated
      by cassette mutagenesis, whereby seven residues of the twelve-residue loop were
      excised and replaced by two glycyl residues. The purified loop-deletion mutant
      was totally devoid of carboxylase activity, but retained substantial catalytic
      competency in the enolization of ribulose bisphosphate (the initial step in the
      overall carboxylase pathway) and in normal processing of the six-carbon
      carboxylated intermediate (the terminal steps in the overall carboxylase
      pathway). Hence, catalytic impairment resides predominantly at the stage of
      carboxylation of the initial enediol(ate), a conclusion compatible with
      mechanistic deductions derived from crystallographic analyses. A critical role of
      loop 6 in the stabilization of the transition state for carboxylation is
      reinforced by the findings that the loop-deletion mutant displays preferentially
      compromised affinity for an analogue of the carboxylated intermediate relative to
      ribulose bisphosphate and that the mutant converts the substrate to a dicarbonyl
      compound as a consequence of beta-elimination of phosphate from the initial
      enediol(ate).

PMID- 7718556
TI  - [Lys(-2)-Arg(-1)]endothelin-1 solution structure by two-dimensional 1H-NMR:
      possible involvement of electrostatic interactions in native disulfide bridge
      formation and in biological activity decrease.
AB  - Addition of the Lys(-2)-Arg(-1) dipeptide, present in the precursor protein, to
      the N-terminus of endothelin-1 (ET-1), to form a 23-residue peptide (KR-ET-1) has
      been shown to greatly improve formation of native disulfide bridges and to
      dramatically decrease biological activity. Conformational analysis was carried
      out on this peptide. During protonation of the carboxyl groups, CD spectra showed
      a decrease in the helical contribution, and NMR spectra displayed strong chemical
      shift modifications, suggesting the importance of electrostatic interactions in
      the KR-ET-1 conformation. CD spectra and two-dimensional NMR experiments were
      performed to investigate the KR-ET-1 three-dimensional structure in water in the
      carboxylic acid and carboxylate states. Distance and angle constraints were used
      as input for distance geometry calculations. The KR-ET-1 carboxylic acid
      conformation was found to be very similar to ET-1, with a helix spanning residues
      9-15 and an unconstrained C-terminal part. In contrast, in the carboxylate state,
      large changes in Arg(-1) and Phe14 chemical shifts and long-range NOEs were
      consistent with a conformation characterized by a helix extension to Leu17 and a
      stabilized C-terminal section folded back toward the N-terminus. In addition,
      thanks to NOEs with Cys11 and Phe14, the Arg(-1) side chain appeared well
      defined. Simulated annealing and molecular dynamics calculations, supported an
      Arg(-1)-Glu10 salt bridge and an electrostatic network involving the charged
      groups of Trp21, Asp18, and Lys(-2). Moreover, stabilization of the KR-ET-1 C
      terminal part is probably reinforced by hydrophobic interactions involving the
      Val12, Tyr13, Phe14, Leu17, Ile19, Ile20, and Trp21 side chains. In vitro, native
      disulfide bond formation improvement observed for KR-ET-1 could be ascribed to
      electrostatic interactions and more specifically to the Arg(-1)-Glu10 salt
      bridge. In vivo, similar interactions could play an important role in the native
      folding of the ET-1 precursor protein. On the other hand, modification in the
      environment and a reduced mobility of the KR-ET-1 Trp21 key residue, when
      compared to ET-1, could explain, at least in part, the strong decrease in
      biological activity.

PMID- 7718557
TI  - cDNA sequence and chromosomal localization of human enterokinase, the proteolytic
      activator of trypsinogen.
AB  - Enterokinase is a serine protease of the duodenal brush border membrane that
      cleaves trypsinogen and produces active trypsin, thereby leading to the
      activation of many pancreatic digestive enzymes. Overlapping cDNA clones that
      encode the complete human enterokinase amino acid sequence were isolated from a
      human intestine cDNA library. Starting from the first ATG codon, the composite
      3696 nt cDNA sequence contains an open reading frame of 3057 nt that encodes a
      784 amino acid heavy chain followed by a 235 amino acid light chain; the two
      chains are linked by at least one disulfide bond. The heavy chain contains a
      potential N-terminal myristoylation site, a potential signal anchor sequence near
      the amino terminus, and six structural motifs that are found in otherwise
      unrelated proteins. These domains resemble motifs of the LDL receptor (two
      copies), complement component Clr (two copies), the metalloprotease meprin (one
      copy), and the macrophage scavenger receptor (one copy). The enterokinase light
      chain is homologous to the trypsin-like serine proteinases. These structural
      features are conserved among human, bovine, and porcine enterokinase. By Northern
      blotting, a 4.4 kb enterokinase mRNA was detected only in small intestine. The
      enterokinase gene was localized to human chromosome 21q21 by fluorescence in situ
      hybridization.

PMID- 7718558
TI  - An SRY mutation causing human sex reversal resolves a general mechanism of
      structure-specific DNA recognition: application to the four-way DNA junction.
AB  - SRY, a genetic "master switch" for male development in mammals, exhibits two
      biochemical activities: sequence-specific recognition of duplex DNA and sequence
      independent binding to the sharp angles of four-way DNA junctions. Here, we
      distinguish between these activities by analysis of a mutant SRY associated with
      human sex reversal (46, XY female with pure gonadal dysgenesis). The substitution
      (168T in human SRY) alters a nonpolar side chain in the minor-groove DNA
      recognition alpha-helix of the HMG box [Haqq, C.M., King, C.-Y., Ukiyama, E.,
      Haqq, T.N., Falsalfi, S., Donahoe, P.K., & Weiss, M.A. (1994) Science 266, 1494
      1500]. The native (but not mutant) side chain inserts between specific base pairs
      in duplex DNA, interrupting base stacking at a site of induced DNA bending.
      Isotope-aided 1H-NMR spectroscopy demonstrates that analogous side-chain
      insertion occurs on binding of SRY to a four-way junction, establishing a shared
      mechanism of sequence- and structure-specific DNA binding. Although the mutant
      DNA-binding domain exhibits > 50-fold reduction in sequence-specific DNA
      recognition, near wild-type affinity for four-way junctions is retained. Our
      results (i) identify a shared SRY-DNA contact at a site of either induced or
      intrinsic DNA bending, (ii) demonstrate that this contact is not required to bind
      an intrinsically bent DNA target, and (iii) rationalize patterns of sequence
      conservation or diversity among HMG boxes. Clinical association of the I68T
      mutation with human sex reversal supports the hypothesis that specific DNA
      recognition by SRY is required for male sex determination.

PMID- 7718559
TI  - Purification and properties of the alkylation repair DNA glycosylase encoded the
      MAG gene from Saccharomyces cerevisiae.
AB  - The MAG gene of Saccharomyces cerevisiae encodes an alkylation repair DNA
      glycosylase whose sequence is homologous to the AlkA DNA glycosylase from
      Escherichia coli. To investigate the biochemical properties of MAG in comparison
      to AlkA, MAG was expressed in E. coli and purified to electrophoretic
      homogeneity. N-Terminal sequencing of the purified protein identified the
      translational start site which corresponded to that predicted previously from the
      nucleotide sequence. Polyclonal antibodies raised against MAG inhibited the
      enzymatic activity of MAG, but not that of AlkA, and vice versa, implying that
      the structures of the active site regions of these enzymes are antigenic, but
      sufficiently different to have different epitopes. Kinetic analysis of base
      excision from DNA exposed to [3H]methyl-N-nitrosourea and [3H]dimethyl sulfate
      showed that MAG was as effective as AlkA in removing 3-methyladenine, 7
      methylguanine, and 7-methyladenine. However, the purified MAG enzyme did not
      catalyze the excision of O2-methylthymine, which is a major substrate for AlkA.
      Furthermore, 3-methylguanine was excised 20-40 times more slowly by MAG than by
      AlkA. The kinetics of 3-methylguanine excision by MAG were found to be similar to
      the low rate of 3-methylguanine excision catalyzed by 3-methyladenine DNA
      glycosylase I (Tag) of E. coli. Expression of MAG in alkA mutant cells did not
      effectively restore alkylation resistance of the mutant as did AlkA itself. It
      thus appears that MAG is a less versatile enzyme than AlkA in spite of the
      sequence relationship and may have a similar function in yeast as the
      nonhomologous Tag enzyme in E. coli.

PMID- 7718560
TI  - A single-stranded DNA binding protein that specifically recognizes cis-acting
      sequences in the replication origin and transcriptional promoter region of
      Tetrahymena rDNA.
AB  - Type I repeat sequences are evolutionarily conserved sequence elements found in
      the replication origin and transcriptional promoter region of the rRNA genes
      (rDNA) in Tetrahymena thermophila. An abundant single-stranded DNA binding
      protein, ssA-TIBF, specifically interacts with the A-rich strand of the Type I
      repeat sequence. Quantitative binding competition experiments performed with
      purified ssA-TIBF demonstrate that the binding site for ssA-TIBF includes
      sequences both within the conserved 33 nt element and in a 3' flanking region:
      addition of the 3' flanking sequence to the Type I repeat oligonucleotide
      increases the binding affinity of ssA-TIBF by nearly 100-fold (apparent Kd = 3.0
      x 10(-10) M). A mutation in the ssA-TIBF binding site previously shown to be the
      determinant of an rDNA replication defect in vivo results in a 25-fold decrease
      in ssA-TIBF binding affinity in vitro. ssA-TIBF also binds with high affinity to
      a copy of the Type I repeat sequence within the essential promoter region defined
      by in vitro transcription assays. The affinity of ssA-TIBF for the promoter
      repeat, which differs from other copies of the repeat at 8 out of 33 positions,
      is at least equal to its affinity for the Type I repeat sequences in the origin
      region. The biochemical properties of ssA-TIBF in vitro suggest that it could
      play a role in both replication and transcription of Tetrahymena rDNA in vivo.

PMID- 7718561
TI  - Influence of neighboring base pairs on the stability of single base bulges and
      base pairs in a DNA fragment.
AB  - Temperature-gradient gel electrophoresis (TGGE) was used to determine the
      relative thermal stabilities of 32 DNA fragments that differ by a single unpaired
      base (base bulge) and 17 DNAs differing by a base pair. Homologus 373 and 372 bp
      DNA fragments differing by a single base pair substitution or deletion were
      employed. Heteroduplexes containing a single base bulge were formed by melting
      and reannealing pairs of 372 and 373 bp DNAs. Product DNAs were separated on the
      basis of their thermal stability by parallel and perpendicular TGGE. The order of
      stability was determined for all single unpaired bases in four different nearest
      neighbor environments: (GXT).(AYC), (GXG).(CYC), (CXA).(TYG), and (TXT).(AYA)
      with X = A, T, G, or C, and Y = no base, or visa versa. DNA fragments containing
      a base bulge were destabilized by 2-3.6 degrees C (+/- 0.2 degrees C) with
      respect to homologous DNAs with complete Watson-Crick base pairing. Both the
      identity of the unpaired base and the sequence of the flanking base pairs
      influenced the degree of destabilization. The range of temperature shift
      correspond to estimated unfavorable free energies from 2.5 to 4.6 kcal/mol.
      Purine base bulges were generally not as destabilizing as pyrimidine base bulges.
      An unpaired base which was identical to one of its adjacent bases generally
      caused less destabilization than an unpaired base with an identity differing from
      its nearest neighbors. This implies that positional degeneracy of an unpaired
      base within a run of two or more identical bases is an important factor effecting
      stability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718562
TI  - Reaction mechanism of T4 endonuclease V determined by analysis using modified
      oligonucleotide duplexes.
AB  - The reaction mechanism of bacteriophage T4 endonuclease V was investigated using
      modified oligodeoxyribonucleotide duplexes containing a cis-syn thymine dimer.
      For the pyrimidine dimer glycosylase step, the formation of a covalent
      intermediate has been proposed. A fluorine atom was attached to the 2'-position
      of the 5'-component of the thymine dimer site, which could stabilize the covalent
      complex and prevent the ring opening of the sugar moiety. The strand cleavage of
      the 12 base pair substrate analog did not occur, although the glycosyl bond was
      cleaved by this enzyme. A covalent enzyme--substrate complex was separated by gel
      electrophoresis under denaturing conditions. It was shown that the enzyme
      molecules were completely converted to a stable complex in the reaction mixture.
      Two mechanisms have been proposed for the beta-elimination step. A 12-mer
      containing a phosphorothioate linkage between adjacent thymidines was prepared.
      The diastereomers were separated, and the absolute configurations were
      determined. After formation of the thymine dimer and 32P-labeling of the 5'
      terminus, these oligonucleotides were annealed to the complementary 12-mer, and
      the reaction rates of the pyrimidine dimer glycosylase step and the overall
      reaction for each duplex were measured under the substrate-saturation conditions.
      The rate constants indicated that the chemical reaction at the beta-elimination
      step was rate-limiting. Since no difference was observed in the rate constants
      for the Rp- and Sp-phosphorothioate substrates, it is concluded that the beta
      elimination reaction is catalyzed, not by the internucleotide phosphate, but by
      an amino acid residue of the enzyme.

PMID- 7718563
TI  - Visualization of nucleosomal substructure in native chromatin by atomic force
      microscopy.
AB  - Intact rDNA minichromosomes from Tetrahymena thermophila were isolated as native
      chromatin and imaged by atomic force microscopy (AFM). AFM measurements of
      condensed rDNA chromatin were consistent with a 30 nm fiber that frequently (87%
      of molecules observed) contained stretches of nucleosome cores arranged in a zig
      zag conformation. Examination of rDNA chromatin in a dispersed conformation by
      tapping mode AFM in low humidity resulted in high resolution images of partially
      dissociated nucleosome cores and associated linker DNA. A majority of these
      nucleosome cores contained six to eight smaller particles with dimensions
      consistent with those of individual histones. Many of the nucleosome cores showed
      a striking resemblance to the wedge (35%), axial (15%), and front (6%) views of
      the nucleosome histone octamer modeled by Arents et al. [Arents, G., Burlingame,
      R. W., Wang, B.-C., Love, W.E., & Moudrianakis, E. N. (1991) Proc. Natl. Acad.
      Sci. U.S.A. 88, 10148-10152]. This direct visualization of histone subunits and
      nucleosomal substructure in native chromatin illustrates the potential use of AFM
      to localize individual proteins in condensed cellular chromatin.

PMID- 7718564
TI  - Substrate and accessory protein requirements and thermodynamics of acetyl-CoA
      synthesis and cleavage in Methanosarcina barkeri.
AB  - Enzymological studies on the multienzyme acetyl-CoA decarbonylase synthase (ACDS)
      complex from Methanosarcina barkeri have been conducted in order to identify and
      characterize physiologically relevant substrates and reactions in acetyl-CoA
      synthesis and decomposition in methanogens. Whereas previous investigations
      employed carbon monoxide as substrate and reducing agent for acetyl-CoA
      synthesis, we discovered that bicarbonate (or CO2) acts as a highly efficient
      carbonyl group precursor substrate in the presence of either hydrogen or
      Ti3+.EDTA as reducing agent. In reactions with Ti3+.EDTA, synthesis of acetyl-CoA
      was strongly dependent on ferredoxin, and in reactions with H2, dependence on
      ferredoxin was absolute. Two major hydrogenases were resolved from the enzyme
      complex preparation by HPLC gel filtration. One of these hydrogenases was shown
      to be active in reconstitution of acetyl-CoA synthesis in CO2-containing
      reactions with H2 as reducing agent. The hydrogenase active in reconstitution was
      capable of reducing ferredoxin, but was unreactive toward the 8-hydroxy-5
      deazaflavin derivative coenzyme F420. In contrast, the hydrogenase that did not
      reconstitute acetyl-CoA synthesis was reactive with F420 but was unable to reduce
      ferredoxin. Further experiments were performed in which the value of the
      equilibrium constant (Keq) was determined for the reaction: H2 + CO2 + CH3-H4SPt
      + CoASH <--> acetyl-CoA + H4SPt + H2O, where CH3-H4SPt and H4SPt stand for N5
      methyl-tetrahydrosarcinapterin and tetrahydrosarcinapterin, respectively. Keq for
      this reaction was found to be 2.09 x 10(6) M-1ATMH2-1 at 37 degrees C.
      Calculations of thermodynamic values for additional, related reactions were made
      and are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718565
TI  - "Dehydrogenase" and "oxidase" reactions of medium-chain fatty acyl-CoA
      dehydrogenase utilizing chromogenic substrates: role of the 3',5'-adenosine
      diphosphate moiety of the coenzyme A thioester in catalysis.
AB  - We undertook a comparative investigation of the medium-chain fatty acyl-CoA
      dehydrogenase (MCAD)-catalyzed reaction utilizing indole-, furyl-, and 4
      (dimethylamino)phenyl-substituted propionyl- and acryloyl-CoAs as potential
      substrate/product pairs. All these propionyl-CoA derivatives undergo MCAD
      catalyzed conversion into their corresponding acryloyl-CoAs via both
      "dehydrogenase" (in the presence of "organic" electron acceptors) and "oxidase"
      (buffer-dissolved oxygen serving as the electron acceptor) pathways [Johnson, J.
      K., Wang, Z. X., & Srivastava, D. K. (1992) Biochemistry 31, 10564-10575]. The
      steady-state kinetic parameters for the enzyme utilizing these substrates reveal
      that the KmS (for the CoA substrates) and kcatS for the dehydrogenase reaction
      are at least an order of magnitude higher than those for the oxidase reaction. As
      with the CoA substrates, the enzyme catalyzes the conversion of indolepropionyl
      pantetheine phosphate (IPPP) into indoleacryloyl pantetheine phosphate (IAPP) via
      these two pathways. However, with IPPP as substrate, the Km (for IPPP) and kcat
      values of the dehydrogenase and oxidase reactions are the same. These, coupled
      with the spectral changes of the enzyme-product complexes as well as the binding
      affinities of the enzyme-substrate/product complexes, lead to the following
      conclusions: (1) The aromatic/heterocyclic group-containing substrates are
      converted into their corresponding products via both the dehydrogenase and the
      oxidase pathways. (2) The 3',5'-ADP moiety of the CoA thioester provides a
      significant fraction of the total binding energy in stabilizing the enzyme
      substrate/product complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718566
TI  - Gramicidin S synthetase 1 (phenylalanine racemase), a prototype of amino acid
      racemases containing the cofactor 4'-phosphopantetheine.
AB  - The biosynthesis of the decapeptide antibiotic gramicidin S in Bacillus brevis
      ATCC 9999 is catalyzed by a multienzyme system consisting of two multifunctional
      proteins, gramicidin S synthetase 1 and 2, encoded by the grsA and grsB genes,
      respectively. Gramicidin S synthetase 1 (phenylalanine racemase, EC 5.1.1.11,
      GS1) racemizes phenylalanine in the thioester-bound stage. The amount of 4'
      phosphopantetheine liberated from highly purified GS1 was determined
      microbiologically using Lacto-bacillus plantarum as the test organism. It matches
      exactly with the amount of L-[14C]phenylalanine covalently incorporated by GS1 as
      thioester. The reaction center of GS1 for L-phenylalanine thiolation and
      racemization was labeled with [3H]iodoacetic acid. After tryptic fragmentation of
      the 3H-carboxymethylated enzyme, the active site peptide for thioester binding
      and racemization of phenylalanine was isolated in pure form by multistep
      methodology and investigated by sequence, amino acid, and mass spectrometric
      analysis. A 4'-phosphopantetheine carrier was found to be attached to the active
      site serine of the consensus motif LGGDSI forming the thiolation site of
      phenylalanine. These specific properties establish GS1 as a prototype of amino
      acid racemases using 4'-phosphopantetheine as a cofactor and yield further
      evidence that multiple Pan carriers are involved in gramicidin S formation. Our
      results are strong evidence for the "multiple carrier model" as a new concept of
      nonribosomal peptide biosynthesis at protein templates as recently proposed
      [Stein, T., et al. (1994) FEBS Lett. 340, 39-44].

PMID- 7718567
TI  - Mechanistic studies on CDP-6-deoxy-L-threo-D-glycero-4-hexulose 3-dehydrase
      identification of His-220 as the active-site base by chemical modification and
      site-directed mutagenesis.
AB  - CDP-6-deoxy-L-threo-D-glycero-4-hexulose 3-dehydrase (E1) purified from Yersinia
      pseudotuberculosis is a pyridoxamine 5'-phosphate (PMP) dependent iron-sulfur
      containing enzyme which catalyzes the C-O bond cleavage at C-3 of its substrate
      leading to the formation of 3,6-dideoxyhexose. This enzyme is rapidly inactivated
      by diethyl pyrocarbonate (DEP) at pH 6.0 and 25 degrees C. The inactivation of E1
      by DEP, which is reversible upon treatment of hydroxylamine, appears to be
      attributable solely to the modification of histidine residues. The fact that
      coincubation of E1 with its substrate gave almost total protection against DEP
      inactivation and that only one less histidine residue was modified in the
      presence of substrate strongly suggested that inactivation is due to the
      modification of only one reactive histidine residue which resides in or near the
      active site of E1 and is critical for E1's activity. Sequence alignment between
      the translated ascC (E1) gene and several representative pyridoxal 5'-phosphate
      (PLP)/PMP dependent enzymes revealed that three of the four invariant residues,
      glycine, aspartate, and arginine found in all other aminotransferases, are
      conserved in the E1 sequence (G169, D191, and R403). However, the highly
      conserved lysine is replaced by a histidine residue (H220) in E1. In order to
      test whether H220 plays an essential role in E1 catalysis, H220N mutant was
      constructed and the encoding protein was found to exhibit nearly identical
      physical characteristics as the wild-type E1. Interestingly, the mutant protein
      had lost most of its catalytic activity, and one less histidine residue was
      modified upon treatment of H220N-mutated protein with DEP. Such a single-point
      mutation also impaired E1's capability of catalyzing the solvent hydrogen
      exchange at C-4' position of the PMP coenzyme. Our findings strongly suggested
      that H220 is most likely the active-site base which abstracts the C-4' proton
      from the PMP-substrate adduct and initiates the catalysis. Furthermore, E1's
      preservation of other invariant residues found in many PLP/PMP dependent enzymes
      allowed a speculation of their roles in E1 catalysis.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7718568
TI  - Enzymatic synthesis of octadecameric saccharides of multiply branched blood group
      I-type, carrying four distal alpha 1,3-galactose or beta 1,3-GlcNAc residues.
AB  - Radiolabeled oligosaccharide constructs were prepared to evaluate carbohydrate
      determinants involved in gamete adhesion in mice. The octasaccharide primer
      GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3(GlcNAc beta 1-3Gal beta 1-4GlcNAc beta
      1-6)Gal beta 1-4GlcNAc (1) was incubated with UDP-GlcNAc and beta 1,6-GlcNAc
      transferase of hog gastric microsomes, producing the tetraantennary
      decasaccharide GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-3[GlcNAc
      beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-6]Gal beta 1-4GlcNAc (2). The
      decasaccharide was then incubated with UDP-Gal and beta 1,4-galactosyltransferase
      from bovine milk, yielding the tetradecasaccharide Gal beta 1-4GlcNAc beta 1
      3(Gal beta 1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-3[Gal beta 1-4GlcNAc beta
      1-3(Gal beta 1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-6]Gal beta 1-4GlcNAc
      (3). Incubation of the tetradecasaccharide 3 with UDP-Gal and alpha 1,3
      galactosyltransferase from bovine thymus gave the octadecameric glycan Gal alpha
      1-3Gal beta 1-4GlcNAc beta 1-3(Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-6)Gal beta
      1-4GlcNAc beta 1-3[Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3(Gal alpha 1-3Gal beta
      1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-6]Gal beta 1-4GlcNAc (4).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7718569
TI  - Oligosaccharide constructs with defined structures that inhibit binding of mouse
      sperm to unfertilized eggs in vitro.
AB  - During fertilization in mice, free-swimming sperm bind to mZP3, an 83-kDa
      glycoprotein present in the egg extracellular coat, the zona pellucida
      [Wassarman, P. M. (1990) Development 108, 1-17]. Mouse sperm recognize and bind
      to a specific class of serine/threonine-linked (O-linked) oligosaccharides
      present on mZP3. After binding to mZP3, sperm undergo a form of cellular
      exocytosis, the acrosome reaction, thereby enabling them to penetrate the zona
      pellucida and fertilize the egg. Thus, gamete interactions in mice are
      carbohydrate-mediated. In this context, we tested 15 O-linked-related
      oligosaccharide constructs with defined structures for their ability to inhibit
      binding of mouse sperm to ovulated eggs and to induce sperm to undergo the
      acrosome reaction in vitro. Thirteen of the oligosaccharides were constructed and
      characterized in our laboratory [Seppo, A., Pentilla, L., Niemela, R., Maaheimo,
      H., Renkonen, O., & Keane, A. (1995) Biochemistry 34, 4655-4661]; two were
      obtained commercially. We found that, while none of the oligosaccharides induced
      sperm to undergo the acrosome reaction, a few of them inhibited binding of sperm
      to eggs at relatively low concentrations (ID50 < 5 microM). In certain cases,
      sperm formed head-to-head aggregates in the presence of the oligosaccharides. The
      results suggest that the ability of oligosaccharides to inhibit binding of sperm
      to eggs is dependent on several parameters, including the size and branching
      pattern of the oligosaccharide, as well as on the nature of the sugar residue at
      the nonreducing end of the oligosaccharide.

PMID- 7718570
TI  - Autocatalytic acylation of phospholipase-like myotoxins.
AB  - Several snake venoms contain a phospholipase A2 in which position 49 in the
      active site is occupied by a lysine or a serine instead of the aspartate residue
      normally found. Although these proteins do not bind Ca2+ and are devoid of
      catalytic activity, they are still highly specific myotoxins and have recently
      been shown to induce membrane leakage by a new type of cytolytic mechanism. Three
      of these toxins, myotoxin II from Bothrops asper, ammodytin L from Vipera
      ammodytes, and the K49 protein from Agkistrodon piscivorus piscivorus, were
      examined for their interaction with fatty acids and were found to bind long-chain
      fatty acids covalently by a rapid, spontaneous, autocatalytic process. The fatty
      acids could be released by treatment with 1 M NH2OH or NaOH, but not with 1 M
      NaCl or by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electron
      spin resonance studies using spin-labeled fatty acids showed that only the
      carboxyl headgroup of the fatty acid was linked to protein amino acid, the carbon
      chain had free mobility and did not bind tightly to the protein surface. Stearic
      acid methyl esters and short-chain fatty acids did not bind to the toxins.
      Acylated myotoxins bound to the surface of liposomes and isolated muscle
      membranes, with the fatty acid moiety inserted into the lipid bilayer and
      possibly acting as an anchor. The phospholipase-like myotoxins represent the
      first group of proteins able to undergo acylation by spontaneous reaction with
      free fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718571
TI  - Potent inhibition of viral fusion by the lipophosphoglycan of Leishmania
      donovani.
AB  - Lipophosphoglycan (LPG) is an amphiphile produced by Leishmania. Its chemical
      structure consists of a hydrophilic flexible polymer of repeating PO4-6Gal beta 1
      4Man alpha 1 units (on average 16 units) linked via a hexasaccharide core to a
      lyso-1-O-alkyl-P1 membrane anchor. In the study of viral fusion we report in this
      paper, we have introduced LPG into human erythrocyte ghost (HEG) membranes, with
      the purpose of understanding how the LPG-induced surface-structural changes may
      modulate the interactions between a viral envelope and the HEG membranes. We have
      found that LPG, when incorporated at very low concentrations into intact human
      erythrocyte membranes, strongly inhibits Sendai virus-induced hemolysis. When
      incorporated into HEGs, it reduces the binding of both Sendai and influenza
      viruses to HEGs; furthermore, it strongly inhibits the overall viral fusion to
      HEGs, being among the most potent known inhibitors. We have also shown that LPG
      stabilizes the bilayer structure of phosphatidylethanolamine against the
      formation of an inverted-hexagonal structure. We suggest that LPG may give rise
      to an effective "steric repulsion" between the viral and HEG membranes, thereby
      modulating some specific modes of interaction between viral-target membranes in
      the overall fusion process; LPG may also modulate the bending rigidity and the
      spontaneous curvature of the HEG membrane in the direction of making the
      destabilization and rearrangement of the underlying lipid bilayer more difficult.

PMID- 7718572
TI  - Evidence for a two-dimensional molecular lattice in subgel phase DPPC bilayers.
AB  - Using a combination of X-ray diffraction data from oriented films and
      multilamellar liposomes of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine
      (DPPC) in the subgel phase, we have established the presence of a 2D molecular
      lattice containing two lipid molecules. The proposed 2D lattice is consistent
      with all the X-ray diffraction data on the subgel phase of DPPC available in the
      literature. In this phase, the DPPC molecules are ordered in the plane of the
      bilayer and are also found to be positionally correlated across a single bilayer
      but not with those in adjacent bilayers. We also present the possible molecular
      arrangements for the proposed lattice.

PMID- 7718573
TI  - Activation by PKC of the Ca(2+)-sensitive guanylyl cyclase in bovine retinal rod
      outer segments measured with an optical assay.
AB  - cGMP and Ca2+ are intracellular messengers in vertebrate rod photoreceptors. cGMP
      is the excitatory messenger, while intracellular free Ca2+ has been implied to be
      (one of) the messenger(s) in the process of light adaptation in vertebrate rod
      photoreceptors. The enzyme guanylyl cyclase (GC, EC 4.6.1.2.) catalyzes the
      reaction GTP-->cGMP + PPi. Bovine retinal rod outer segments (ROS) contain a
      particulate GC which is inhibited by an increase in free Ca2+ in the
      submicromolar range, although the precise molecular mechanism underlying this
      inhibition is unclear. We have developed an optical enzyme-coupled assay to study
      regulation of the particulate GC endogenous to bovine ROS. The particulate GC
      exhibited a Ca(2+)-inhibited (IC50 83-144 nM) activity of 13-23 nmol of PPi/(min
      (mg of rhodopsin)). ATP increased the maximal velocity of GC by about 2-fold, and
      this increase was inhibited by the specific PKC inhibitors chelerythrine and the
      pseudosubstrate-based peptide inhibitor PKC R10-31N. When the factor that
      mediated the ATP-dependent increase in GC rate was removed by washing, the ATP
      dependent increase in GC rate could be reestablished by addition of purified,
      constitutively active PKC.

PMID- 7718574
TI  - Identification of sequences mediating guanylyl cyclase dimerization.
AB  - Deletion mutagenesis was used to identify sequences required for dimerization and
      enzymatic activity of the intracellular domain of the membrane guanylyl cyclase,
      GC-A. The intracellular domain of GC-A contains a protein kinase-like domain near
      its amino terminus, a guanylyl cyclase catalytic domain near its carboxyl
      terminus, and, between these domains, a region of unknown function predicted to
      form an amphipathic alpha-helix. Gel filtration analysis of deletion mutants of
      the GC-A intracellular domain suggested that a 43 amino acid sequence within the
      interdomain region was both necessary and sufficient for dimerization and was
      required for guanylyl cyclase catalytic activity. The ability of this sequence to
      mediate protein dimerization was confirmed in the yeast two-hybrid system, in
      which its fusion to the lexA DNA-binding domain and to the VP16 transcriptional
      activation domain led to their dimerization and consequent activation of a lexA
      HIS3 gene. Thus, we have identified sequences responsible for dimerization of the
      intracellular domain of a guanylyl cyclase and shown that they are required for
      enzyme activity. Modulation of their interaction may be important in guanylyl
      cyclase activation.

PMID- 7718575
TI  - Reconstructed 19 kDa catalytic domain of gelatinase A is an active proteinase.
AB  - Matrix metalloproteinases share high protein sequence homology and have defined
      domain structures. Gelatinases have a unique 19 kDa fibronectin-like insert in
      the catalytic domain. A synthetic gene was made to express the catalytic domain
      of human gelatinase A (GCD), in which two polypeptide fragments of the catalytic
      domain were joined with deletion of the insert. The synthetic gene was highly
      expressed in Escherichia coli, and the 19 kDa GCD was purified to homogeneity
      after in vitro refolding. The GCD showed activity at a pH range of 5.5-9 in
      cleavage of the thiopeptolide Ac-Pro-Leu-Gly-thioester-Leu-Leu-Gly-OEt with
      optimal activity at neutral pH (Km = 134 microM and kcat = 16 s-1 at pH 7.0). The
      activity required both zinc and calcium ions, but high concentration of zinc ion
      showed inhibition. Several stromelysin catalytic domain inhibitors inhibited the
      GCD with similar specificity. The GCD cleaved the fluorogenic peptides Mca-Pro
      Leu-Gly-Leu-Dpa-Ala-Arg-NH2 and Dnp-Pro-Leu-Gly-Leu-Trp-Ala-D-Arg-NH2 with
      catalytic efficiency close to full length human gelatinase A. The reconstructed
      GCD cleaves not only thiopeptolide and peptide substrates but also protein
      substrates such as gelatin. These results are consistent with the notion that
      gelatinases have the same structure for the catalytic domain as other matrix
      metalloproteinases like stromelysins and collagenases.

PMID- 7718576
TI  - Substitutions of isoleucine residues at the adenine binding site activate horse
      liver alcohol dehydrogenase.
AB  - The contributions of isoleucine residues 224 and 269 of horse liver alcohol
      dehydrogenase to binding of the adenine moiety of NAD and to catalysis were
      studied by replacing Ile-224 with glycine (I224G) and Ile-269 with serine
      (I269S). The kinetic mechanisms of wild-type and both mutated liver enzymes were
      ordered. Affinities for several adenosine derivatives were decreased 5-50-fold by
      both substitutions. The I269S mutation differentially destabilized binding of the
      complete coenzyme, as affinities for NAD+ and NADH were decreased about 60-fold
      with the I224G enzyme and 350-fold for the I269S enzyme. The I269S substitution
      increased the rate constants for the conformational change that occurs when NAD+
      binds. The maximum velocities for ethanol oxidation increased 7-fold with the
      I224G enzyme and 26-fold with the I269S enzyme due to the faster release of NADH.
      Hydride transfer limits the rate of oxidation of ethanol by the I269S enzyme.
      Inhibition constants for the substrate analogues, 2,2,2-trifluoroethanol and N
      methylformamide, and catalytic efficiencies (V/Km) for ethanol and acetaldehyde
      were not changed by the mutations, indicating that binding of the adenosine
      moiety of the coenzyme is not necessarily coupled to the subsequent reaction of
      substrates.

PMID- 7718577
TI  - pH, ionic strength, and temperature dependences of ionization equilibria for the
      carboxyl groups in turkey ovomucoid third domain.
AB  - Two-dimensional NMR spectroscopy has been used to monitor the pH dependences of
      proton chemical shifts for turkey ovomucoid third domain (OMTKY3). Sample pH was
      varied from 7.0 to 1.4 in order to determine the apparent pKa values of all six
      carboxyl groups in OMTKY3. At 35 degrees C and in the presence of 10 mM KCl, the
      pKa values for Asp 7, Glu 19, and Asp 27 (< 2.6, 3.2, and < 2.3, respectively)
      are more than 1 pH unit below those for model compounds. The pKa values for Glu
      10 (4.1) and Glu 43 (4.7) show more modest deviations from model compound data.
      The low pKa for the alpha-carboxyl group of Cys 56 (< 2.5) is attributable, at
      least in part, to acidification by the disulfide group. Fitting the data to a
      modified Hill equation [Markley, J. L. (1975) Acc. Chem. Res. 8, 70-80] reveals
      little evidence for interactions between the acidic groups; most Hill
      coefficients fall between 0.8 and 1.2, with outlying values usually obtained with
      data that describe incomplete transitions. Most of the very low pKa values show
      increases in the presence of 1.0 M KCl but, with the exception of that for
      glutamate 19, remain well below model compound values. pH-dependent changes in
      amide proton chemical shifts permitted identification of hydrogen bonds involving
      the side chains of Asp 7, Glu 19, and Asp 27, which may partially explain the low
      pKa values for these groups. These hydrogen bonds, two of which involve side
      chains that are well exposed to solvent, were previously identified in high
      resolution X-ray studies of turkey ovomucoid third domain [Fujinaga, M.,
      Sielecki, A. R., Read, R. J., Ardelt, W., Laskowski, M., Jr., & James, M. N. G.
      (1987) J. Mol. Biol. 195, 397-418]. Results of additional experiments performed
      at 15, 25, and 40 degrees C suggest that apparent ionization enthalpies for all
      carboxyl groups in OMTKY3 are about 0 +/- 2 kcal/mol. In the accompanying paper
      [Swint, L., & Robertson, A. D. (1995) Biochemistry 34, 4724-4732], the pH
      dependence of OMTKY3 stability is described and compared to expectations based on
      the pKa values described herein.

PMID- 7718578
TI  - Hydrogen bonds and the pH dependence of ovomucoid third domain stability.
AB  - Thermal denaturation of turkey ovomucoid third domain (OMTKY3) has been monitored
      with differential scanning calorimetry (DSC) and circular dichroism in H2O and
      D2O, pH 1.5 to 5 and ionic strength 0.01 to 0.71. Results from DSC experiments
      are in good agreement with spectroscopic studies [Swint, L., & Robertson, A.D.
      (1993) Protein Sci. 2, 2037-2049] and fit well to the two-state unfolding model.
      The average ratio of calorimetric to van't Hoff enthalpies is 0.99 +/- 0.03 (n =
      16), and the average value of delta Cp is 620 +/- 20 cal/(mol K) (n = 7). The
      free energy of unfolding (delta G(u)o) increases in the presence of salt at both
      pH 1.5 and 4.5. This stabilization is not due to ion binding and probably results
      from screened repulsive interactions between the cationic groups of OMTKY3. At
      very low ionic strength, the change in delta G(u)o from pH 1.5 to 4.5, delta
      delta GpHo, is 3.5 +/- 0.2 kcal/mol. Few interactions between ionizing groups are
      affected by the addition of 200 mM KCl; delta delta GpHo decreases by only 0.4 +/
      0.3 kcal/mol. Comparison of delta delta GpHo with values calculated from the
      pKas of all six carboxyl groups in OMTKY3 [Schaller, W.S., & Robertson, A.D.
      (1995) Biochemistry 34, 4714-4723] suggests that some pKas in the denatured state
      may be lower than those of model compounds. Moreover, calculated values of delta
      delta GpHo are very sensitive to modest changes in the cooperativity of proton
      binding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718579
TI  - Highly specific oxidative cross-linking of proteins mediated by a nickel-peptide
      complex.
AB  - The Ni(II) complex of the tripeptide NH2-Gly-Gly-His-COOH is shown to mediate
      efficient protein-protein cross-linking in the presence of oxidants such as oxone
      and monoperoxyphthalic acid. Only proteins that associate specifically in
      solution are cross-linked under these conditions. Preliminary probes of the
      mechanism of the reaction suggest that the active intermediate may be a high
      valent metal complex that attacks aromatic amino acids.

PMID- 7718580
TI  - Bioactivity of metallothionein-3 correlates with its novel beta domain sequence
      rather than metal binding properties.
AB  - Human and mouse metallothionein-3 (MT-3) molecules exhibit the same metal binding
      stoichiometry with Zn(II), Cd(II), or Cu(I) as MT-1 or MT-2 molecules, suggesting
      that MT-3 consists of two domains enfolding separate polymetallic clusters. The
      kinetic reactivities of Zn(II) complexes of MT-3 with the chelator
      ethylenediaminetetraacetic acid (EDTA) or the thiol reagent dithiobis(2
      nitrobenzoic acid) (DTNB) resembles the reactivity of ZnMT-1. Furthermore, the
      candidate alpha and beta domain peptides of human MT-3 are very similar to MT-1
      domain peptides in the reactivity of Zn(II) complexes. Zn(II) complexes of human
      and mouse MT-3 inhibit the survival of rat cortical neurons cultured in the
      presence of an Alzheimer's disease brain extract. Inhibitory activity is unique
      to the MT-3 isoform and is a property of the N-terminal beta domain. The
      inhibitory activity of the 32-residue MT-3 beta domain is abolished by a double
      mutation within the beta domain resulting in the conversion of the C-P-C-P
      sequence to either C-S-C-A or C-T-C-T. Thus, the bioactivity arises from a novel
      structure of the N-terminal beta domain of MT-3 and not any unusual metal-binding
      properties.

PMID- 7718581
TI  - Expression of blood group Lewis b determinant from Lewis a: association of this
      novel alpha (1,2)-L-fucosylating activity with the Lewis type alpha (1,3/4)-L
      fucosyltransferase.
AB  - Blood group H type 1 [Fuc alpha (1,2)Gal beta (1,3)GlcNAc beta-->] is known as
      the precursor structure of the blood group determinant, Lewis b [Fuc alpha
      (1,2)Gal beta (1,3)(Fuc alpha (1,4))GlcNAc beta-->]. Recently, a new biosynthetic
      route for Lewis b from Lewis a [Gal beta (1,3)(Fuc alpha (1,4))GlcNAc-->] was
      identified in human gastric carcinoma cells, colon carcinoma Colo 205, and
      ovarian tumor. The present study demonstrates the association of this new type of
      alpha (1,2)-L-fucosyltransferase (FT) activity with the Lewis-type alpha (1,3/4)
      L-FT as follows: (i) the alpha (1,4)- and novel alpha (1,2)-FT activities of Colo
      205 were much less inhibited than the alpha (1,3)-FT activity by N-ethylmaleimide
      [Ki(microM) = 714.0, 119.0, and 6.5 respectively]. (ii) The alpha (1,4)- and
      novel alpha (1,2)-FT activities emerged from a Sephacryl S-200 column in
      identical positions. (iii) A specific inhibitor (copolymer from 3-sulfo
      Galbeta(1,3)GlcNAcbeta-O-allyl and acrylamide) of alpha(1,4)-FT activity
      inhibited both alpha(1,4)- and alpha(1,2)-FT activities in Sephacryl S-200 column
      effluent to almost the same extent (approximately 80%); (iv) separation of the
      Lewis-type alpha(1,3/4)-FT from the plasma-type alpha(1,3)-FT by specific elution
      of the affinity column (bovine IgG glycopep-Sepharose) with lactose and further
      purification on a Sephacryl S-100 HR column showed that (a) the alpha(1,3)-FT
      activity was the inherent capacity of the Lewis-type FT (Colo 205 fraction L)
      since approximately 90% of both the alpha(1,4)- and alpha(1,3)-FT activities is
      inhibited by the copolymer, (b) the unique ability of catalyzing the alpha(1,2)-L
      fucosylation of Gal in Lewis a structure and also the alpha(1,3)-L-fucosylation
      of Glc in lactose-based structure belonged to the Lewis type enzyme (Colo 205
      fraction L), (c) a measurement of the [14C]fucosyl products arising from the two
      acceptors Galbeta(1,3)(4,6-di-O-Me)GlcNAcbeta-O-Bn and 3-sulfo
      Galbeta(1,3)GlcNAcbeta-O-A1 (specific for alpha(1,2) and alpha(1,4),
      respectively) taken in the same incubation mixture showed mutual inhibition by
      the acceptors ([Km for the alpha(1,4)-specific acceptor, 3-sulfo
      Galbeta(1,3)GlcNAcbeta-O-A], increased from 32 to 50 microM in the presence of
      7.5 mM Galbeta(1,3)(4,6-di-O-Me)GlcNAcbeta-O-Bn, whereas Ki for the mutual
      inhibition of alpha(1,2)-FT activity by the former was 102 microM], and (d) the
      Lewis-type FT, in contrast to the plasma type FT, was highly effective in
      fucosylating complex glycopeptides. (iv) A cloned FT (FT III:Lewis type) and the
      Colo 205 Lewis-type FT (fraction L) showed similar activities toward various
      acceptors; the enzymatic product resulting from the action of cloned FT on
      Galbeta(1,3)(Fucalpha(1,4))GlcNAc-beta-O-Bn was identified by FAB mass
      spectrometry as the difucosyl compound. (v) An examination of six human cell
      lines indicated that the novel alpha(1,2)-FT activity associates with the
      alpha(1,4)-FT activity.

PMID- 7718582
TI  - Characterization of human and rat intestinal trefoil factor produced in yeast.
AB  - Intestinal trefoil factor (ITF) from human (hITF) and rat (rITF) have been
      produced in Saccharomyces cerevisiae. The DNA encoding the two peptides were
      cloned by polymerase chain reactions (PCR) from a human normal colon library and
      a rat small intestinal epithelial cell library. Recombinant plasmids were
      constructed to encode a fusion protein consisting of a hybrid leader sequence and
      the rat and human ITF sequences, respectively. The leader sequence used serves to
      direct the fusion protein into the secretory (and processing) pathway of the
      cell. The secreted recombinant hITF was found in a monomer and a dimer form,
      whereas the rITF was only secreted as a dimer. The secreted peptides were
      purified by a combination of ionic exchange chromatography and preparative HPLC.
      From 8 L of yeast fermentation broth, 256 mg of hITF (monomer) and 133 mg of hITF
      (dimer) were isolated, and from 8.7 L of fermentation broth, 236 mg of rITF
      (dimer) was isolated. The structure of hITF (monomer), hITF (dimer), and rITF
      (dimer) was determined by amino acid analyses, peptide mapping, sequence
      analyses, and electrospray mass spectrometry analyses. In hITF (monomer) six of
      the seven cysteines are disulfide-linked to form 3 disulfide bridges. Mass
      analysis indicated that the last cysteine residue (Cys-57) did not exist as free
      (-SH) cysteine, but have reacted with cysteine to form an S-S linked cystine.
      Sequence and mass spectrometry analyses as well as peptide mapping showed that
      the dimer form of both hITF and rITF is mediated by a disulfide bridge between
      Cys-57 residues of two monomers.

PMID- 7718583
TI  - Reduction of phenoxyl radicals by thioredoxin results in selective oxidation of
      its SH-groups to disulfides. An antioxidant function of thioredoxin.
AB  - Thioredoxin is an important cellular redox buffer. In this report, we describe
      the reaction of thioredoxin with phenoxyl radicals. The vicinal sulfhydryls of
      the bis(cysteinyl) active site sequence reduced phenoxyl radicals released in
      horseradish peroxidase-catalyzed oxidation of phenol. Redox cycling of phenol was
      accompanied by selective oxidation of thioredoxin sulfhydryls to disulfides.
      HPLC/UV-vis measurements showed that the SH:phenol oxidation ratio was 15:1 under
      the conditions used. At the end of the reaction, oxidized thioredoxin was
      quantitatively recovered in the reduced form with dithiothreitol. Oxidation of
      sulfhydryls to sulfoxy derivatives, oxidation of other amino acid residues, and
      formation of covalent adducts with phenolic metabolites (quinones) were not
      detected by LC-MS. While the thiyl radical of glutathione was readily detected
      with the spin trap 5,5-dimethyl-1-pyrroline N-oxide, no ESR-detectable DMPO-thiyl
      adducts formed during the oxidation of thioredoxin. Similarly, oxidation of
      vicinal sulfhydryls of dihydrolipoic acid did not produce DMPO-thiyl spin
      adducts, indicating that fast intramolecular cyclization to disulfide occurred
      with thioredoxin. Measurements of the superoxide dismutase-sensitive
      chemiluminescence response of lucigenin demonstrated that thioredoxin oxidation
      was accompanied by release of superoxide, most likely via disulfide radical anion
      mediated one-electron reduction of oxygen. We propose that formation of
      disulfides is characteristic of the phenoxyl radical-catalyzed oxidation of
      vicinal sulfhydryls in both small thiols and disulfide-forming oxidoreductases.
      Reversibility of the phenoxyl radical-catalyzed modification of thioredoxin may
      be responsible for its function as an efficient cytosolic antioxidant.

PMID- 7718584
TI  - Oxygen equilibrium properties of nickel(II)-iron(II) hybrid hemoglobins cross
      linked between 82 beta 1 and 82 beta 2 lysyl residues by bis(3,5
      dibromosalicyl)fumarate: determination of the first two-step microscopic Adair
      constants for human hemoglobin.
AB  - We have previously reported that cross-linked asymmetric Ni(II)-Fe(II) hybrid
      hemoglobin, XL[alpha (Fe) beta (Fe)][alpha (Ni) beta (Ni)], in which the alpha 1
      beta 1 dimer containing ferrous protoporphyrin IX and the adjacent alpha 2 beta 2
      dimer containing nickel(II) protoporphyrin IX were cross-linked between Lys-82
      beta 1 and Lys-82 beta 2 by reaction with bis(3,5-dibromosalicyl)fumarate,
      represents an adequate model for determination of the alpha 1 beta 1 oxygenation
      properties of native hemoglobin [Shibayama, N., Imai, K., Morimoto, H., & Saigo,
      S. (1993) Biochemistry 32, 8792-8798]. To extend the approach using cross-linked
      Ni(II)-Fe(II) hybrids to all possible pathways for initial-half oxygenation of
      hemoglobin, we have prepared three other types of cross-linked Ni(II)-Fe(II)
      hybrids, carrying nickel(II) protoporphyrin IX in two subunits and ferrous
      protoporphyrin IX in the other two subunits, and have determined the two-step
      oxygen equilibrium curves of the ferrous subunits within these cross-linked
      hybrids. For the first step of oxygenation, the alpha subunit shows about 3-fold
      higher affinity than the beta subunit at all pH values examined, indicative of a
      significant functional heterogeneity of the subunits in deoxyhemoglobin. For the
      second step of oxygenation, the cooperativity represented by the Hill coefficient
      (nmax) increases in the order of beta 1 beta 2 (nmax = 1.36), alpha 1 beta 1
      (nmax = 1.41), alpha 1 beta 2 (nmax = 1.64), and alpha 1 alpha 2 (nmax = 1.72) at
      pH 7.4 in the presence of 0.1 M Cl- at 25 degrees C.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7718585
TI  - Structural organization of the Ni and (4Fe-4S) centers in the active form of
      Desulfovibrio gigas hydrogenase. Analysis of the magnetic interactions by
      electron paramagnetic resonance spectroscopy.
AB  - The Desulfovibrio gigas hydrogenase is a typical (NiFe) hydrogenase containing a
      Ni center and three FeS centers, one [3Fe-4S] and two [4Fe-4S] clusters. When the
      enzyme is activated under hydrogen gas, the Ni center becomes paramagnetic,
      giving a characteristic electron paramagnetic resonance (EPR) signal with g
      values at 2.19, 2.14 and 2.01, the Ni-C signal. Two redox states of the enzyme
      can be prepared, in which the [4Fe-4S] clusters are either diamagnetic or
      paramagnetic. In this latter state, the magnetic coupling between metal centers
      induces both the appearance at low temperature of a complex EPR spectrum, the
      split Ni-C signal, and a significant enhancement of the relaxation rates of the
      Ni center. Good simulations of the split Ni-C signal recorded at three different
      microwave frequencies (X-band, Q-band, and S-band) are obtained by using a model
      based on a point dipole approximation of the dipolar and exchange interactions
      between paramagnets. The spectral analysis demonstrates that only one [4Fe-4S]1+
      cluster is significantly coupled to the Ni site and provides a detailed
      description of the relative arrangement of the two centers. In addition, the
      magnetic characteristics of this [4Fe-4S]1+ cluster can be deduced from the
      simulations. Moreover, the spin-spin and spin-lattice relaxation times of the
      interacting centers were measured in the two redox states of the enzyme, either
      by power saturation and pulsed EPR experiments at low temperature or from the
      broadening of the EPR lines at higher temperature. The relaxation behavior of the
      Ni center is well explained by using in the theoretical analysis, the set of
      structural and magnetic parameters deduced from the spectral simulations. Our
      structural conclusions on the active D. gigas hydrogenase are compared to the
      preliminary data of a low-resolution crystal structure of the oxidized enzyme
      [Volbeda, A., Piras, C., Charon, M. H., Hatchikian, E. C., Frey, M., & Fontecilla
      Camps, J. C. (1993) News Lett. Protein Crystallogr. 28, 30-33].

PMID- 7718586
TI  - Crystal structure of cathepsin B inhibited with CA030 at 2.0-A resolution: A
      basis for the design of specific epoxysuccinyl inhibitors.
AB  - Crystals of cysteine protease human cathepsin B inhibited with CA030 (ethyl ester
      of epoxysuccinyl-Ile-Pro-OH) [Murata, M., et al. (1991) FEBS Lett. 280, 307-310;
      Towatari, T., et al. (1991) FEBS Lett. 280, 311-315] were isomorphous to a
      previous published structure of cathepsin B [Musil, D., et al. (1991) EMBO J. 10,
      2321-2330]. The crystal structure of the complex was refined at 2.0-A resolution
      to an R-value of 0.194. CA030 is well-defined in the electron density. The Ile
      Pro-OH part of CA030 mimics a substrate P1' and P2' residues. The structure thus
      reveals for the first time a substratelike interaction in the S1' and S2' sites
      of a papain-like cysteine protease. The CA030 ethyl ester group occupies the S2
      site. The structure confirms the role of residues His 110 and His 111 as the
      receptors of a peptidic substrate C-terminal carboxylic group. The structure
      suggests that an epoxysuccinyl fragment can be used to extend binding into primed
      and nonprimed substrate binding sites of a papain-like cysteine protease.

PMID- 7718587
TI  - Charge recombination reactions in photosystem II. I. Yields, recombination
      pathways, and kinetics of the primary pair.
AB  - Recombination reactions of the primary radical pair in photosystem II (PS II)
      have been studied in the nanosecond to millisecond time scales by flash
      absorption spectroscopy. Samples in which the first quinone acceptor (QA) was in
      the semiquinone form (QA-) or in the doubly reduced state (presumably QAH2) were
      used. The redox state of QA and the long-lived triplet state of the primary
      electron donor chlorophyll (3P680) were monitored by EPR. The following results
      were obtained at cryogenic temperatures (around 20 K). (1) the primary radical
      pair, P680+Pheo-, is formed with a high yield irrespective of the redox state of
      QA. (2) The decay of the primary pair is faster with QA- than with QAH2 and could
      be described biexponentially with t1/2 approximately 20 ns (approximately
      65%)/150 ns (approximately 35%) and t1/2 approximately 60 ns (approximately
      35%)/250 ns (approximately 65%), respectively. The different kinetics may be due
      to electrostatic and/or magnetic effects of QA- on charge recombination or due to
      conformational changes caused by the double reduction treatment. (3) The yield of
      the triplet state 3P680 was high both with QA- and QAH2. (4) The triplet decay
      was much faster with QA- [t1/2 approximately 2 microseconds (approximately
      50%)/20 microseconds (approximately 50%)] than with QAH2 [t1/2 approximately 1 ms
      (approximately 65%)/3 ms (approximately 35%)]. The short lifetime of the triplet
      with QA- explains why it was not detected earlier. The mechanism of triplet
      quenching in the presence of QA- is not understood; however it may represent a
      protective process in PS II. (5) Almost identical data were obtained for PS II
      enriched membranes from spinach and PS II core preparations from Synechococcus.
      Room temperature optical studies were performed on the Synechococcus preparation.
      In samples containing sodium dithionite to form QA- in the dark, EPR controls
      showed that multiple excitation flashes given at room temperature led to a
      decrease of the QA-Fe2+ signal, indicating double reduction of QA. During the
      first few flashes, QA- was still present in the large majority of the centers. In
      this case, the yield of the primary pair at room temperature was around 50%, and
      its decay could be described monoexponentially with t1/2 approximately 8 ns (a
      slightly better fit was obtained with two exponentials: t1/2 approximately 4 ns
      (approximately 80%)/25 ns (approximately 20%).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7718588
TI  - Charge recombination reactions in photosystem II. 2. Transient absorbance
      difference spectra and their temperature dependence.
AB  - Absorbance difference spectra of the transient states in photosystem II (PS II)
      have been examined in the Qv absorption region between 660 and 700 nm. The
      P680+Pheo-/P680Pheo, 3P680/P680, and P680+QA-/P680QA spectra were measured in O2
      evolving PS II core complexes from Synechococcus and PS II-enriched membrane
      fragments from spinach. The low-temperature absorbance difference spectra vary
      only slightly between both PS II preparations. The 3P680/P680 spectrum is
      characterized by a bleaching at 685 nm at 25 K and indicates weak exciton
      coupling with neighboring pigment(s). We conclude that P680 absorbs at 685 nm in
      more intact PS II preparations at cryogenic temperature. The difference spectra
      of the radical pairs are strongly temperature dependent. At low temperature the
      P680+QA-/P680QA- spectrum exhibits the strongest bleaching at 675 nm whereas the
      P680+Phe-/P680Pheo spectra show two distinct bleaching bands at 674 and 684 nm.
      It is suggested that an electrochronic red shift resulting in a bleaching at 675
      nm and an absorbance increase at about 682 nm dominates the spectral features of
      the charge-separated states. On the basis of the present results and those in the
      literature, we conclude that the interactions between the pigments and especially
      the organization of the primary donor must be quite different in PS II compared
      to bacterial reaction centers, although the basic structural arrangement of the
      pigments might be similar. Spectral data obtained with samples in the presence of
      singly and doubly reduced QA indicate that the primary photochemistry in PS II is
      not strongly influenced by the redox state of QA at low temperature and confirm
      the results of the accompanying paper [Van Mieghem, F. J. E., Brettel, K.,
      Hillmann, B., Kamlowski, A., Rutherford, A. W., & Schlodder, E. (1995)
      Biochemistry 34, 4798-4813]. The spectra of the primary radical pair and the
      reaction center triplet obtained with more intact PS II preparations differ
      widely from those of D1/D2/cyt b-559 complexes. In the latter sample, where 3P680
      formation results in a bleaching at 680 nm, the P680+Pheo-/P680Pheo spectrum
      shows only one broad bleaching band at about 680 nm, and the main bleaching due
      to photoaccumulation of Pheo- at 77 K appears at 682 nm instead of 685 nm in PS
      II core complexes. This indicates that the removal of the core antenna which is
      accompanied by the loss of QA causes also structural changes of the reaction
      center.

PMID- 7718589
TI  - Effects of substitution of tyrosine 57 with asparagine and phenylalanine on the
      properties of bacteriorhodopsin.
AB  - Tyrosine 57 is one of the residues present in the retinal binding pocket and is
      conserved in all the halophilic retinal proteins. We have studied mutants of
      bacteriorhodopsin, expressed in Halobacterium salinarium, in which tyrosine 57 is
      replaced by an asparagine (Y57N) or phenylalanine (Y57F). In Y57N the photocycle
      proceeds only up to the L intermediate; no M is formed at neutral pH. The
      lifetime of L intermediate is extremely long, ca. 500 ms. Proton release is
      severely affected in both the mutants which suggests that Y57 is associated with
      the proton release pathway. By comparing the pH-induced absorption changes in the
      UV in Y57N and Y57F with those in the wild-type (WT), we determined that the pKa
      of Y57 is 10.2. In Y57F, which shows M formation, the rate constant of the L-->M
      transition is pH dependent (pKa 8.7) suggesting that Y57 is probably not the
      residue that normally controls the transition into the alkaline photocycle. Y57
      is either part of the counterion complex or in close proximity to D85 since its
      mutation influences the pKa of Asp85. In Y57F the pKa of D85 is approximately 4.9
      (compared to approximately 2.9 in the WT). The Y57N mutant shows two pKa's in the
      purple to blue transition, approximately 3.8 and < 1. In the presence of
      hydroxylamine, at neutral pH, Y57N is stable in the dark but bleaches very
      rapidly upon illumination compared to the WT. Since the lifetime of L
      intermediate is long in Y57N, we suggest that the Schiff base becomes accessible
      to hydroxylamine in this state.

PMID- 7718590
TI  - Cytochrome P-450 transfer from adrenocortical submitochondrial particles to
      liposome membranes.
AB  - The transfer of cytochrome P-450 from bovine adrenocortical submitochondrial
      particles (smp) to unilamellar liposome membranes was investigated using a table
      top ultracentrifuge. Submitochondrial particles were incubated with liposome
      membranes at 25 degrees C and precipitated by ultracentrifugation at 200000g for
      a few minutes at 25 degrees C. All liposome vesicles were recovered in the
      supernatant. Almost no proteins were detected in the supernatant when only smp
      were incubated and centrifuged. SDS-PAGE revealed one main protein band for the
      supernatant when smp were incubated with liposome vesicles at 25 degrees C. This
      band was reactive to anti-P-450scc IgG. Inaccuracy in time for kinetic studies of
      the transfer was less than 0.5 min. Transfer of P-450scc from smp to liposome
      membranes was further demonstrated by the decrease in side-chain cleavage
      activity of smp for endogenous cholesterol after incubation. Cytochromes P-450
      accounted for about 70% of the transferred proteins in the liposome membranes,
      the amount of which increased exponentially with the incubation time. The inverse
      value of the relaxation time of the transfer increased linearly with the smp
      concentration and decreased hyperbolically with the liposome concentration. These
      results coincide with a mechanism by which cytochrome P-450 dissociates from smp
      membranes, diffuses, and binds to the liposome membranes. In the transfer of
      cytochrome P-450, the dissociation from smp membranes was deduced to be the rate
      limiting step.

PMID- 7718591
TI  - Preferential distribution of the fluorescent phospholipid probes NBD
      phosphatidylcholine and rhodamine-phosphatidylethanolamine in the exofacial
      leaflet of acetylcholine receptor-rich membranes from Torpedo marmorata.
AB  - The distribution of the two fluorescent phospholipid analogs across acetylcholine
      receptor (AChR)-rich membranes from Torpedo marmorata has been studied by a
      combination of nonradiative fluorescence resonance energy transfer using
      fluorescent lipid probes and quenching of their fluorescence with Co2+ and 2,4,6
      trinitrobenzenesulfonic acid. The fluorescent lipid analogs were supplied to the
      AChR-rich membrane or liposome suspension by simply injecting ethanol solutions
      of the probes into the medium. The efficiency of the fluorescence energy transfer
      between NBD-labeled phosphatidylcholine and rhodamine-labeled ethanolamine
      glycerophospholipids was measured in model membranes prepared in such a way that
      the probes could be targeted at the same or opposite halves of the bilayer, and
      the results were compared with those obtained for native AChR-rich membranes. It
      is shown that NBD-PC and Rho-PE can be efficiently (95%) incorporated into AChR
      rich membranes and liposomes. On the basis of the comparison with model
      liposomes, the energy transfer experiments suggest a preferential exofacial
      location of the parental phospholipids in the native AChR-rich membrane.
      Fluorescence quenching with Co2+ and TNBS showed these two phospholipid analogs
      to be located predominantly in the outer leaflet of the bilayer in AChR-rich
      membranes. From the Co2+ quenching of the lipid analogs, it was also possible to
      calculate the surface potential of the outer leaflet of the membrane as being on
      the order of -15 mV.

PMID- 7718592
TI  - Interaction of the isolated transmembrane domain of diphtheria toxin with
      membranes.
AB  - Insertion of diphtheria toxin's T (transmembrane) domain into the endosomal
      membrane under acidic conditions is known to promote translocation of its
      catalytic domain across the membrane and into the cytosol. The T domain, a
      cysteine-free bundle of alpha-helices, was expressed as a discrete protein in
      Escherichia coli and purified. The isolated domain was stable and largely
      monomeric at pH 8.0. Like the holotoxin it bound the hydrophobic fluorophore, 2-p
      toluidinylnaphthalene 6-sulfonate, upon acidification, but the transition pH was
      higher than with the holotoxin (pH 5.6 vs 5.1) and broader, reflecting the
      absence of interdomain interactions. The domain also permeabilized large
      unilamellar vesicles under acidic conditions, as demonstrated by release of
      entrapped solutes. Mutant forms of T domain, each with a single residue replaced
      by cysteine, were derivatized with a thiol-reactive nitroxide-containing spin
      label and analyzed by electron paramagnetic resonance (EPR). EPR spectra and
      solvent accessibilities of the labels at pH 8.0 were consistent with the
      environments predicted from the toxin's crystallographic structure. Acidification
      in the presence of large unilamellar vesicles caused a nitroxide label at
      position 332 on helix TH8 to move from a buried site in the water soluble state
      to a lipid-exposed surface site at a depth of approximately 15 A within the
      bilayer. This is consistent with the concept that the TH8-TH9 helix pair inserts
      into the bilayer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718593
TI  - Conformational transitions of the sarcoplasmic reticulum Ca-ATPase studied by
      time-resolved EPR and quenched-flow kinetics.
AB  - We have used time-resolved electron paramagnetic resonance (EPR) and quenched
      flow kinetics in order to investigate the dynamics of Ca-ATPase conformational
      changes involved in Ca2+ pumping in sarcoplasmic reticulum (SR) membranes at 2
      degrees C. The Ca-ATPase was selectively labeled with an iodoacetamide spin label
      (IASL), which yields EPR spectra sensitive to enzyme conformational changes
      during ATP induced enzymatic cycling. The addition of ATP, AMPPCP, CrATP, or ADP
      decreased the rotational mobility of a fraction of the probes, indicating a
      distinct protein conformational state corresponding to this probe population,
      while Pi under conditions producing "backdoor" phosphorylation produced no
      spectral change. Transient changes in the amplitude of the restricted component
      associated with the pre-steady state of Ca2+ pumping were detected with 10 ms
      time resolution after an [ATP] jump produced by laser flash photolysis of caged
      ATP in the EPR sample. The laser energy was adjusted to generate 100 microM ATP
      from 1 mM caged ATP. At 0.1 M KCl, the EPR transient consisted of a brief initial
      lag phase, a monoexponential phase with a rate of 20 s-1, and a decay back to the
      initial intensity after the ATP had been consumed. Raising [KCl] from 0.1 to 0.4
      M slowed the rate of the exponential phase from 20 to 6 s-1. Lowering the pH from
      7 to 6, which increased the rate of caged ATP photolysis, eliminated the lag but
      did not change the apparent rate of the EPR signal rise. Parallel acid quenched
      flow experiments conducted at 0.1 M KCl and 100 microM ATP produced fast (50-58 s
      1) and slow (20 s-1) phases of phosphoenzyme formation. Increasing [KCl] from 0.1
      to 0.4 M decreased the rate of the slow phase of phosphorylation from 20 to 5 s
      1, without affecting the fast phase. The close correlation between the slow phase
      of phosphorylation and the exponential phase of the EPR signal suggests that the
      spin probe monitors a conformational event associated with phosphoenzyme
      formation in a population of catalytic sites with delayed kinetics. We propose
      that this constraint is imposed by conformational coupling between the catalytic
      subunits in a Ca-ATPase oligomer and that, consequently, the EPR signal reflects
      changes in quaternary protein structure as well as changes in secondary and
      tertiary structure associated with ATP-dependent phosphorylation.

PMID- 7718594
TI  - Sedimentation studies on the kinesin motor domain constructs K401, K366, and
      K341.
AB  - Bacterial expressed kinesin motor domains hydrolyze ATP and promote microtubule
      dependent motility. It has routinely been assumed that motor domain preparations
      are monomeric on the basis of the presumption that dimerization is mediated by
      the stalk region. However, experimental verification of the oligomeric state of
      the kinesin construct is required to interpret the results from single-molecule
      motility assays as well as presteady-state kinetic experiments. We have measured
      directly the state of assembly of three conventional kinesin motor domain
      constructs-K401, K366, and K341, comprising the N-terminal 401, 366, and 341
      amino acids, respectively, of the Drosophila kinesin heavy chain-by sedimentation
      velocity and sedimentation equilibrium methods in an analytical ultracentrifuge.
      K401 (MW of ADP complex, 45,532) is a predominantly a dimer with a sedimentation
      coefficient, s020,w, of 5.06 S, but it is able to self-associate by means of a 1
      2-4 mechanism into higher oligomers. Molecular weight measurements establish the
      dissociation constant for dimerization at 37 +/- 17 nM in the presence of ATP.
      The dissociation constant in the presence of ADP is 35 +/- 26 nM and in the
      presence of AMPPNP is 42 +/- 28 nM. The construct K366 (MW of ADP complex,
      41,404) is a monomer (measured MW, 41,768 +/- 1219) at concentrations below 4
      microM K366, with a sedimentation coefficient, s020,w, of 3.25 S. At higher
      concentrations, there is evidence for a weak association of K366 to a 1-2-4-8
      model with a slight preference for octamer formation. The smallest construct,
      K341 (MW of ADP complex, 38,274), is a monomer (measured MW, 38,191 +/- 734) up
      to at least 10 microM total K341 concentration with a sedimentation coefficient,
      s020,w, of 2.9 S. Thus, the dimerization domain either is between amino acid
      residues 367 and 401 or is strongly affected by the removal of this region.
      Higher oligomers of K401 form by a mechanism involving dimers of dimers, and
      suggest that native kinesin may also undergo self-association. These results have
      important implications for the interpretation of ATP-dependent motility assays.

PMID- 7718595
TI  - 1-beta-D-arabinofuranosylcytosine activates tyrosine phosphorylation of p34cdc2
      and its association with the Src-like p56/p53lyn kinase in human myeloid leukemia
      cells.

PMID- 7718596
TI  - Cation-sensitive pore formation in rehydrated erythrocytes.
AB  - Rehydration of red blood cells (RBC) in isotonic media after dehydration in
      hypertonic electrolyte or nonelectrolyte saline leads to their posthypertonic
      hemolysis (PH). Ca2+ ions at a concentration of more than 5 mM stimulated
      hemolysis of RBC treated by hypertonic sucrose but not NaCl if rehydration was
      carried out in the presence of cations. Zn2+ produced a more complex response of
      stimulation followed by inhibition as a concentration is increased. Mg2+, Ca2+,
      Zn2+, EDTA and sucrose exhibited only inhibition when added to isotonic NaCl
      media immediately after onset of rehydration or later on. At low ionic strength
      inhibition produced by divalent cations was markedly reduced and sucrose was
      ineffective. An equimolar concentration of EDTA abolished the inhibition of PH by
      Zn2+ ions if they were introduced into the isotonic media after the cells, but
      activated hemolysis when rehydration was carried out in the presence of ions. The
      same divalent cations prevented shape transformation and hemolysis induced by
      melittin if they interacted with the plasma membrane prior to the addition of
      melittin. Subsequent chelation of cations by EDTA triggers the full sequence of
      events characteristic to the action of melittin alone and resulted in cell
      spherulation followed by hemolysis. Inhibition of melittin-induced hemolysis
      produced by all cations was reversible because EDTA abolished the action of
      divalent cations and even stimulated hemolysis in isotonic sucrose. Similarities
      in the mode of action of divalent cations and EDTA on posthypertonic hemolysis
      which is attributed to endogenous stimuli and melittin-induced hemolysis as far
      as the exogenous agent is concerned imply that in both cases common intrinsic
      mechanisms are involved in the process of cation-sensitive pore formation in
      erythrocyte membranes, while differences indicate that more complex pores are
      formed during posthypertonic injury.

PMID- 7718598
TI  - Generation, modulation and maintenance of the plasma membrane asymmetric
      phospholipid composition in yeast cells during growth: their relation to surface
      potential and membrane protein activity.
AB  - During growth a cyclic exposure of anionic phospholipids to the external surface
      of the plasma membrane was found. The surface charge density (sigma) increased
      gradually reaching a maximum in the first 5 h of growth and returned gradually to
      their initial value at the end of the logarithmic phase of growth (10-12 h).
      Phosphatidylinositol, that determines to a large extent the magnitude of the
      sigma, increased 83% in the yeast cells during the first 4 h of growth and
      returned gradually to their initial level at 10-12 h. During the stationary phase
      (12-24 h), both sigma and the anionic/zwitterionic phospholipid ratio, remained
      without any significant variation. The high-affinity H-linked glutamate transport
      system that behaves as a sensor of the changes in the membrane surface potential
      (phi) increased its activity in the first 5 h and then decreased it, following
      with great accuracy the sigma variations and remained without changes during the
      stationary phase of growth. The phosphatidylserine (PS) relative concentration in
      the cells (9.0%) did not significantly change during the whole growth curve, but
      their asymmetric distribution varied, contributing to the changes in sigma. PS
      facing the outer membrane surface increased 2.45-times during the first 5 h of
      growth and then returned to their original value at the end of the log phase (12
      h). Phosphatidylcholine (PC) remained constant during the whole growth curve
      (50%), while phosphatidylethanolamine (PE) decreased 3-fold in the first 4 h and
      then increased to its original value at 10 h. Interestingly, PE at the outer
      membrane surface remained constant (3% of the total phospholipids) during the
      whole growth curve. During growth yeast cells change their phospholipid
      composition originating altered patterns of the plasma membrane phospholipid
      composition and IN-OUT distribution. This dynamic asymmetry is involved in the
      regulation of the surface potential and membrane protein activity.

PMID- 7718597
TI  - Neutral polymers elicit, and antibodies to spectrin, band 4.1 protein and
      cytoplasmic domain of band 3 protein inhibit the concanavalin A-mediated
      agglutination of human erythrocytes.
AB  - Concanavalin A (Con A) is known to agglutinate human erythrocytes if the cells
      are pre-treated with a proteinase or neuraminidase. We report that untreated
      cells can also be made to agglutinate with the lectin if the lectin-bound cells
      are treated with anti-Con A antibodies, or if a neutral polymer such as serum
      albumin, polyvinylpyrrolidone or Ficoll is added. Thus, Con A falls in the
      category of 'incomplete' lectins. The polymer induces Con A-agglutinability
      without altering the receptor number, or deformability of the cells. If the
      polymer is sequestered within erythrocyte ghosts, Con A is unable to agglutinate
      them; but the presence of the polymer only on the outer surface (as in intact
      cells) or on both the surfaces permits agglutinability. Thus, the site of the
      polymer effect resides on the outer surface of the membrane. The polymer,
      however, is unable to induce agglutinability in erythrocyte vesicles, whose
      membrane lacks skeletal proteins. The result suggests a positive role for the
      membrane skeleton in the process of agglutination brought about by the polymer,
      as is true also for the agglutination of proteinase-treated cells. In order to
      obtain detailed information on the proteins participating in agglutination,
      monospecific antibodies to spectrins, band 4.1 protein, ankyrin and the
      cytoplasmic domain of band 3 protein were internalized in erythrocytes. It is
      found that anti-spectrin and anti-band 3 cytoplasmic domain, but not their Fab's,
      inhibit the Con A-mediated agglutinability partially, and anti-4.1 antibodies, as
      well as the Fab's, inhibit the agglutinability substantially. Anti-ankyrin,
      however, was without any effect. The results confirm a positive role for the
      membrane skeleton in the Con A-mediated agglutination of normal erythrocytes in
      the presence of a neutral polymer, or in proteinase treated cells. We also
      provide evidence for requirement of Mg-ATP in the agglutination process.

PMID- 7718599
TI  - The possible self-down-regulation of calpain triggered by cell membranes.
AB  - In order to confirm whether the binding sites for mu-calpain on the inner surface
      of erythrocyte membranes are substrate proteins themselves, we examined the
      binding properties of mu-calpain to mu-calpain-pretreated inside-out membranes.
      When native mu-calpain was incubated with mu-calpain-pretreated membranes,
      however, newly added calpain was degraded rapidly in a time- and Ca(2+)-dependent
      manner. Although the degradation of mu-calpain was not inhibited by various
      proteinase inhibitors, it was strongly inhibited by digestible substrates for
      calpain that possess the ability to inhibit the binding of mu-calpain to
      erythrocyte membranes. On the other hand, when mu-calpain inactivated by N
      ethylmaleimide was incubated with mu-calpain-pretreated membranes, no degradation
      was observed. These results indicate that the degradation of mu-calpain occurs on
      the surface of mu-calpain-modified membranes and that it depends on the
      autoproteolytic activity of mu-calpain itself. It seems likely that the
      autoproteolytic activity of mu-calpain is accelerated markedly by some
      component(s) exposed on the surface of membranes during the pretreatment with mu
      calpain. The possibility is thus proposed that cell membranes possess the ability
      to down-regulate calpain to protect cell membranes from overdegradation by
      excessively bound calpain. The active factor(s) in the membranes that can
      accelerate the autoproteolytic degradation of mu-calpain could be almost
      completely removed from mu-calpain-modified membranes by treatment with Triton X
      100.

PMID- 7718600
TI  - Design of immunoliposomes directed against human ovarian carcinoma.
AB  - Factors (protein/lipid ratio, pH of incubation medium, incubation time, anchor
      molecule density in the bilayer) affecting the covalent binding of anti-ovarian
      carcinoma Fab' to liposomes containing the anchor molecule MPB-PE (N-(4-(p
      maleimidophenyl)butyryl)phosphatidylethanolamine) were explored. Standard
      experimental conditions were chosen and information on the relevant
      physicochemical parameters of the liposome dispersions was collected (mean
      particle diameter, size distribution, charge). The reproducibility of standard
      immunoliposomes prepared in subsequent batches in terms of Fab' binding, particle
      size and charge was established. In addition, preservation of immunoreactivity,
      no marker loss, and no aggregation/fusion was found for the standard
      immunoliposomes over a period of at least 3 weeks at 4 degrees C. In vitro up to
      35,000 immunoliposomes were estimated to bind per human ovarian carcinoma cell.
      Internalization of the immunoliposomes could not be demonstrated. Electron
      micrographs showed binding of specific immunoliposomes to human ovarian carcinoma
      cells growing intraperitoneally in athymic nude mice.

PMID- 7718601
TI  - Recognition and clearance of liposomes containing phosphatidylserine are mediated
      by serum opsonin.
AB  - Liver uptake of liposomes containing phosphatidylserine was studied in a single
      pass liver perfusion system and found to be serum dependent. The effectiveness of
      serum in mediating liposome uptake by the liver depends on liposomes size. Large
      liposomes appeared to be opsonized more efficiently and, therefore, taken up more
      by the liver than the smaller ones. The effects of liposomes size on liver uptake
      did not occur in the absence of serum. Treatment of serum at 56 degrees C for 30
      min abolished the serum activity, suggesting the involvement of complement
      components. Inhibition of the hemolytic activity of complement through the
      alternative pathway by PS-containing liposomes suggests that components in this
      pathway are responsible for liposome opsonization. Liposomes containing
      phosphatidic acid, phosphatidylglycerol, and dicetyl phosphate compete in
      different degrees for serum components which mediate the liver uptake of PS
      containing liposomes. These results suggest that the opsonization of liposomes by
      serum opsonins are the determining factors for the recognition and clearance of
      liposomes by the RES. Complement components are most likely involved in this
      process. The results presented here are relevant to the use of liposomes as drug
      delivery vehicle in vivo and to the PS-mediated clearance of red blood cells from
      the blood circulation.

PMID- 7718603
TI  - Effects of magnesium plus vanadate on partial reactions of the Ca(2+)-ATPase from
      human red cell membranes.
AB  - Under conditions in which pretreatment with Mg2+ plus vanadate activate the
      Ca(2+)-ATPase, the initial rate of phosphorylation of the enzyme increased from
      141 to 259 pmol/mg protein per s while the steady-state level of phosphoenzyme
      lowered from 1.9 to 1.1 pmol/mg protein. The drop in phosphoenzyme level was
      caused by incubation and washing during treatment rather than by vanadate. The
      data allowed to estimate a turnover number for the enzyme that raised by 170%
      after pretreatment. The results show that the activation of the Ca(2+)-ATPase by
      Mg2+ plus vanadate is due to changes in the kinetic properties of the enzyme.

PMID- 7718602
TI  - Colocalization of Rh polypeptides and the aminophospholipid transporter in
      dilauroylphosphatidylcholine-induced erythrocyte vesicles.
AB  - Cytoskeleton-free vesicles released from human red blood cells (RBC) transport
      exogenously supplied aminophospholipid analogues from the vesicle's outer to
      inner leaflet at rates comparable to those of normal RBC (Beleznay et al. (1993)
      Biochemistry 32, 3146-3152). Because polypeptides associated with the Rh blood
      group system have been implicated in the transbilayer movement of
      phosphatidylserine (PS), we investigated the relationship and co-localization of
      the aminophospholipid translocase and Rh in dilauroylphosphatidylcholine-induced
      RBC vesicles. The transbilayer movement of fluorescent (NBD-PS) and
      photoactivatable (125I-N3-PS) PS in RBC vesicles was ATP-and temperature
      dependent. Inhibition of PS transport by sulfhydryl reagents could be
      accomplished by direct vesicle treatment or by treating RBC before vesiculation.
      In the case of diamide- and pyridyldithioethylamine-mediated inhibition, NBD-PS
      transport could be restored by reduction with dithiothreitol, indicating that the
      movement of the PS transporter into the emerging vesicle was independent of the
      oxidative status of membrane sulfhydryls. The presence of Rh polypeptides in the
      vesicles was verified by direct immunoprecipitation of isotopically-labeled Rh
      and semi-quantified by antibody adsorption assays. Similar to the movement of the
      PS transporter, localization of Rh polypeptides in the vesicle membrane was
      independent of the red cell's oxidative status. These results show that the PS
      translocase and Rh-related proteins colocalize in RBC vesicles suggesting that
      these proteins may be members of a multicomponent complex that plays a role in
      lipid movement and the generation of membrane lipid asymmetry.

PMID- 7718604
TI  - Na/K competitive transport selectivity of (221)C10-cryptand: effects of pH and
      carrier concentration.
AB  - The kinetics of the competitive transport of Na+ and K+ ions across the membrane
      of large unilamellar vesicles (LUV) were determined when transport was induced by
      (221)C10-cryptand, an ionizable mobile carrier. The experiments were performed at
      various pH values (7.7 and 8.7) and carrier concentrations (0.1, 0.5 and 1.0
      microM) in order to quantify the effects of these parameters on the Na/K
      competitive transport selectivity of this mobile carrier. At any given pH and
      carrier concentration, the apparent affinity of (221)C10 for Na+ was higher and
      less dependent on the concentration of the other competing ion than that for K+.
      The Na/K competitive transport selectivity (SC(Na/K)) of (221)C10 increased
      linearly with the Na+ concentrations, decreased hyperbolically with increasing
      those of K+ and was independent of the pH and of the carrier concentration. In
      equimolecular ionic mixtures, this competitive selectivity amounted to about 1.5
      and when the pH rose, the carrier selectivity for Na+ over K+ ions was enhanced
      by cation competition compared to transport of cations as unique substrates.
      Equations were established to describe the variations of the competitive
      transport selectivity (SC) of cryptands, and for comparison of their
      noncompetitive selectivity (SNC), with the ionic concentrations, the Michaelis
      parameters of the cations and the pH. The reaction order in Na+ (n(Na)) increased
      significantly with decreasing the pH and the K+ concentration. The results are
      discussed in terms of the structural, physico-chemical and electrical
      characteristics of carriers and complexes.

PMID- 7718605
TI  - Differential signal transduction pathways regulating interleukin-2 synthesis and
      interleukin-2 receptor expression in stimulated human lymphocytes.
AB  - In human peripheral blood lymphocytes stimulated via the T-cell antigen
      receptor/CD3 complex IL-2 synthesis and cellular proliferation were effectively
      inhibited by a concentration of ouabain as low as 50 nM, whilst the expression of
      high affinity IL-2 receptors was not influenced. Binding of the monoclonal
      antibody, BMA 031 to the T-cell antigen receptor/CD3 complex resulted in a
      bimodal activation of protein kinase C. The activation of protein kinase C-alpha
      in the early phase of T-lymphocyte activation was not affected by 50 nM ouabain,
      in contrast sustained activation of protein kinase C-beta, between 90-240 min of
      stimulation was completely abolished by the cardiac glycoside. When protein
      kinase C was directly activated by PMA + ionomycin, 50 nM ouabain was ineffective
      in inhibiting protein kinase C activation, as well as subsequent IL-2 synthesis,
      suggesting that the glycoside interfered with signal transducing mechanism(s)
      upstream of the activation of protein kinase C. Ouabain had no influence on the
      elevation of intracellular calcium concentration in BMA 031 stimulated
      lymphocytes, ruling out the possibility that it interfered with the T-cell
      antigen receptor dependent phosphatidylinositol response. In contrast,
      lysophosphatide acyltransferase catalysed elevated incorporation of
      polyunsaturated fatty acids was effectively inhibited by low concentrations of
      ouabain in BMA 031-stimulated T-lymphocytes, whereas stimulation with PMA +
      ionomycin had no influence on the plasma membrane phospholipid fatty acid
      metabolism. These results suggest, that differential signal transduction pathways
      are involved in the activation of protein kinases C-alpha and -beta. They
      implicate that elevated incorporation of polyunsaturated fatty acids into plasma
      membrane phospholipids might contribute to sustained activation of protein kinase
      C-beta, and establish a link between activation of protein kinase C-beta and
      induction of IL-2 synthesis in human lymphocytes.

PMID- 7718606
TI  - The effect of dimethylsulfoxide on the substrate site of Na+/K(+)-ATPase studied
      through phosphorylation by inorganic phosphate and ouabain binding.
AB  - To obtain further information on the role of H2O at the substrate site of
      Na+/K(+)-ATPase, we have studied the enzymes reaction with P(i) and ouabain in
      40% (v/v) Me2SO (dimethylsulfoxide). When the enzyme (E) was incubated with
      ouabain (O) for 5 min in a 40% (v/v) Me2SO-medium with 5 mM MgCl2 and 0.5 mM KCl
      (but no phosphate), ouabain was bound (as EO). Subsequent incubation with P(i)
      showed that E, but not EO, was rapidly phosphorylated (to EP). Long-time
      phosphorylation revealed that EO is also phosphorylated by P(i) albeit very
      slowly (t1/2 about 60 min) and that binding of ouabain to EP also is very slow.
      The EOP complex is stable, i.e., the t1/2 for the loss of P(i) is >> 60 min in
      contrast to about 1 min in water. These results in 40% Me2SO are distinctly
      different from what would be obtained in a watery milieu: ouabain would bind
      slowly and inefficiently in the absence of P(i), and ouabain would catalyse
      phosphorylation from P(i) rather than retard it. Equilibrium binding of
      [3H]ouabain to E and EP in water or 40% Me2SO confirmed these observations: Kdiss
      in water is 11 microM and 12 nM for EO and EOP, respectively, whereas in Me2SO
      they are 112 nM and 48 nM. It is suggested that the primary effect of the lowered
      water activity in 40% Me2SO is a rearrangement of the substrate site so that it
      also in the absence of P(i) attains a transition state configuration
      corresponding to the phosphorylated conformation. This would be sensed by the
      ouabain binding site and lead to high affinity ouabain binding in the absence of
      P(i).

PMID- 7718607
TI  - Effect of the kinetics of temperature variation on Saccharomyces cerevisiae
      viability and permeability.
AB  - The variation rate of the temperature increase was found to have a great effect
      on the viability of Saccharomyces cerevisiae subjected to heat perturbations
      between 25 degrees C and 50 degrees C. A low intensity of the increase rate of
      temperature could maintain an important viability of the cells (about 34% of the
      initial population) with regard to the corresponding viability (about 1%)
      observed after a sudden step change for the same final temperature level of 50
      degrees C. A cell volume reduction more important (22% of the initial volume) has
      been observed in cells submitted to a heat shock than for the cells which have
      been submitted to a slow kinetic of temperature increase (9%). Such an
      observation allowed to propose a relation between the membrane permeability and
      the kinetics of temperature variation.

PMID- 7718608
TI  - Steady-state nonmonotonic concentration profiles in the unstirred layers of
      bilayer lipid membranes.
AB  - Catalytic reactions in the unstirred layers near bilayer lipid membranes can
      induce nonmonotonic concentration profiles near the membrane surface. In the case
      of transmembrane diffusion of a substrate immediately followed by its conversion
      due to the presence of an aqueous soluble enzyme the size of the unstirred layer
      defined in terms of the concentration gradient at the membrane surface does not
      correspond to the width of the aqueous layer adjacent to the membrane where the
      concentration differs from the bulk phase concentration. Deducing of flux values
      or convection parameters from the concentration gradient at zero distance from
      the membrane gives misleading results. An empirical equation for the estimation
      of the size of the concentration boundary layer is proposed. It was derived from
      pH profiles registered with the help of a microelectrode near a planar bilayer
      lipid membrane surrounded by a buffer solution containing at one side of the
      membrane acetaldehyde and sodium acetate and at the other side alcohol
      dehydrogenase. Since this parameter equals to the thickness of the unstirred
      layer in the case of exponential concentration profiles it may be applied to
      estimate both mass transfer restrictions and kinetic of diffusion limited
      reactions occurring in the immediate membrane vicinity regardless the complexity
      of the system under investigation.

PMID- 7718609
TI  - Rotational dynamics of luteinizing hormone receptors and MHC class I antigens on
      murine Leydig cells.
AB  - We have examined the molecular motions of luteinizing hormone (LH) receptor and
      the Major Histocompatibility Complex Class I antigen on murine Leydig cells.
      Using time-resolved phosphorescence anisotropy methods, erythrosin (ErITC)
      derivatized ovine luteinizing hormone (oLH) bound to the LH receptor appears
      rotationally mobile with rotational correlation times of 19.6 +/- 1.3
      microseconds, 13.3 +/- 2.4 microseconds, 9.5 +/- 0.7 microseconds and 4.7 +/- 0.5
      microseconds at 4 degrees C, 15 degrees C, 25 degrees C and 37 degrees C,
      respectively. Rotational correlation times for human chorionic gonadotropin (hCG)
      occupied LH receptors were similar to those of the ErITC-oLH occupied receptor at
      each temperature. In addition, both oLH- and hCG-occupied LH receptors were
      laterally mobile in fluorescence photobleaching recovery experiments with
      diffusion coefficients at 29 degrees C of (5.8 +/- 0.9) x 10(-10) cm2 s-1 and
      (2.9 +/- 0.4) x 10(-10) cm2 s-1, respectively. We also measured the rotational
      correlation time of Class I antigen on murine Leydig cells using ErITC
      derivatized 34-12-2S, an anti-Class I monoclonal antibody. Because there was no
      decay of the anisotropy function at 4 degrees C, 15 degrees C, 25 degrees C or 37
      degrees C in the absence of oLH or following preincubation of Leydig cells with 1
      nM oLH, it appears that Class I is rotationally immobile on the 1 ms timescale of
      our experiments. This result is consistent with the presence of Class I antigen
      in large molecular weight structures and may be the result of Class I self
      aggregation. Further, treatment of cells with anti-Class I antibody had no effect
      on either basal or oLH-stimulated testosterone secretion. Thus, it appears that
      this anti-Class I antibody is not LH-mimetic on murine Leydig cells.

PMID- 7718610
TI  - Lysosomal sulfate transport: inhibitor studies.
AB  - Sulfate derived from the degradation of macromolecules is released from lysosomes
      via a carrier mediated process. In order to further characterize this process,
      recognized inhibitors of the erythrocyte band 3 anion transporter were examined
      for their effects on the lysosomal system. Studies with band 3 transport site
      inhibitors such as DIDS, SITS and phenylglyoxal indicated that, similar to the
      case for the band 3 protein, the lysosomal transporter has critical lysine and
      arginine residues. Band 3 translocation pathway or channel blocking inhibitors
      had mixed effects on the lysosomal system. 1,2-Cyclohexanedione, which covalently
      modifies a band 3 arginine residue distinct from that modified by phenylglyoxal,
      inhibited lysosomal sulfate transport. In contrast, the potent band 3 inhibitor
      dipyridamole had no effect on lysosomal sulfate transport indicating that there
      are some structural differences between the erythrocyte and lysosomal anion
      transporters. The band 3 translocation inhibitors niflumic acid and
      dinitrofluorobenzene were both effective inhibitors of the lysosomal system.
      Cupric ion inhibited sulfate transport while Ca2+, Co2+, Mg2+, Mn2+, and Zn2+ had
      no inhibitory effects. Exposure of intact lysosomes to trypsin largely ablated
      transport of sulfate. This information should be useful in efforts to further
      elucidate the structure and function of the lysosomal sulfate transporter.

PMID- 7718611
TI  - IGF-II receptors in luminal and basolateral membranes isolated from pars
      convoluta and pars recta of rabbit proximal tubule.
AB  - The binding of 125I-labeled insulin-like growth factor-II (125I-IGF-II) to
      luminal and basolateral membrane vesicles isolated from pars convoluta and the
      straight part (pars recta) of rabbit proximal tubule was investigated. Analyses
      of the binding data by use of the general stoichiometric binding equation
      revealed, that in all preparations IGF-II was bound to one high-affinity binding
      site and other sites with lower affinities. The specificity of the high-affinity
      125I-IGF-II binding to the membrane vesicles assessed by displacement by
      unlabeled IGF-II, IGF-I and insulin showed that IGF-I displaced 125I-IGF-II in
      the range 22.5-47.9 nM (IC50) whereas insulin did not effect 125I-IGF-II binding
      at all. beta-Galactosidase inhibited the 125I-IGF-II binding with half-maximal
      inhibition of 20-30 nM beta-galactosidase. D-Mannose 6-phosphate increased the
      binding of 125I-IGF-II and reversed the inhibitory effect of beta-galactosidase.
      Analyses of 125I-IGF-II binding curves in the presence of beta-galactosidase or D
      mannose 6-phosphate demonstrated that none of these compounds changed the binding
      affinity of 125I-IGF-II for the membrane vesicles. The IGF-II/M6P receptor
      content in the luminal membranes was in the range 0.21-0.34 pmol IGF-II/M6P
      receptor per mg protein and very low compared to 2.27-2.86 pmol IGF-II/M6P
      receptor per mg protein in basolateral membranes.

PMID- 7718612
TI  - Transport of glycine and lysine on the chloride-dependent beta-alanine (B0,+)
      carrier in rabbit small intestine.
AB  - Transport of glycine, lysine and beta-alanine in rabbit, guinea pig and rat small
      intestine has been examined by measurements of the unidirectional influx across
      the brush border membrane of the intact epithelium. In rabbit distal ileum the
      chloride-dependent fraction of glycine transport, and all sodium- and chloride
      dependent lysine transport is carried on the beta-alanine carrier. Lysine
      eliminates all saturable, sodium-independent transport of glycine. The saturable,
      sodium-dependent, and lysine resistant influx of glycine is characterized by a
      K1/2Gly of 60 mM. Glycine transport in the mid intestine of the guinea pig is
      chloride-independent and in the rat only a minute fraction may be chloride
      dependent. These species do not possess an equivalent of the rabbit beta-alanine
      carrier. In conclusion, glycine transport in rabbit distal ileum is by the sodium
      dependent carrier of neutral amino acids, by the sodium-independent lysine
      carrier, and by the sodium- and chloride-dependent beta-alanine carrier which
      closely resembles the B0,+ carrier described in mouse blastocysts. All sodium
      dependent lysine transport in rabbit distal ileum is by the chloride- and sodium
      dependent beta-alanine carrier. It is proposed that the beta-alanine carrier in
      rabbit distal ileum be renamed the B0,+ carrier.

PMID- 7718613
TI  - Inhibition of lysosomal acid sphingomyelinase by agents which reverse multidrug
      resistance.
AB  - An increasing body of evidence appears to implicate the lipid bilayer of
      multidrug resistant (MDR) cells with P-glycoprotein activity. Several cationic
      amphiphilic drugs (CADs) have been extensively described as modulators of MDR.
      These same agents are also known to (1) inhibit lysosomal acid sphingomyelinase
      (ASmase), a phospholipid degrading enzyme, and/or (2) induce phospholipidosis in
      animal tissues or cultured cell lines. In this report, we randomly selected 17
      CADs and evaluated their potency in modulating MDR in the murine MDR P388/ADR
      leukemia cell line. We compared these results with their ability to inhibit
      ASmase and observed a significant dose-dependent linear relationship (95% central
      confidence interval), between ASmase inhibition and MDR reversal. This approach
      permitted us to identify three new modestly potent chemosensitizers:
      trimipramine, desipramine, and mianserine. Modulation of MDR was not cell line
      specific, since CADs at 10 microM increased doxorubicin (DOX) and vinblastine
      (VBL) (but not methotrexate, MTX) cytotoxicity in both P388/ADR and the human MDR
      cell lines MES-SA/Dx5 and K562/R7, but not in the parental drug-sensitive cells.
      Although all chemosensitizing CADs at 10 microM significantly increased Rhodamine
      123 (Rho-123) accumulation in the human leukemia MDR cell line K562/R7 and most
      presented significant displacement of the photoaffinity labelling probe
      iodoarylazidoprazosin, no correlation between these observations and the ability
      of CADs to sensitize MDR cells to DOX and VBL was found. In conclusion, our study
      strongly suggests that the chemosensitizing potency of agents such as CADs may be
      due to a dual mechanism of action: direct antagonism of P-gp activity and
      indirect modulation of P-gp activity through the disruption of cellular lipid
      metabolism.

PMID- 7718614
TI  - Evidence for the key role of the adipocyte cGMP-inhibited cAMP phosphodiesterase
      in the antilipolytic action of insulin.
AB  - Enhancement of cAMP degradation by increased cGMP-inhibited cAMP
      phosphodiesterase (cGI-PDE) activity is thought to be an important component of
      the mechanism whereby insulin counteracts catecholamine-induced lipolysis in
      adipocytes. In this study the selective cGI-PDE inhibitor OPC3911 was used to
      evaluate this role of cGI-PDE activation in intact rat adipocytes with special
      reference to changes in cAMP levels measured as cAMP-dependent protein kinase
      (cAMP-PK) activity ratios. OPC3911 completely blocked (IC50 = 0.3 microM) the
      maximal inhibitory effect of insulin on noradrenaline-induced lipolysis and the
      net dephosphorylation of hormone-sensitive lipase and other intracellular target
      proteins for insulin action, whereas insulin-induced lipogenesis was not changed.
      The effect of OPC3911 on cAMP-PK activity ratios at different levels of lipolysis
      achieved by noradrenaline stimulation revealed that the reduction of cAMP-PK
      caused by 1 nM insulin was completely blocked by 3 microM OPC3911. The effect of
      OPC3911 was not due to an excessive increase in cellular cAMP resulting in
      'supramaximal' lipolysis unresponsive to insulin. These data demonstrate that
      reduction in cAMP levels by the activation of cGI-PDE may be sufficient to
      account for the antilipolytic action of insulin.

PMID- 7718615
TI  - Purification and partial amino acid sequencing of a fructosyllysine-specific
      binding protein from cell membranes of the monocyte-like cell line U937.
AB  - The ability of short-term in vitro glycated albumin to react with monocytes or
      the monocyte-like cells U937 is due to the Amadori adduct fructosyllysine. Two
      binding proteins of about 100 and 200 kDa have been previously described to
      interact specifically with the monocyte-like cell line U937. Detergent extracts
      from U937 cell membranes were used to purify the 100kDa protein by ion exchange
      chromatography, fructosyllysine-Sepharose affinity chromatography and SDS-PAGE.
      Six amino acids from the N-terminal end and two peptide sequences of 14 and 15
      amino acids were identical with the N-terminus and the positions 349 to 362 and
      610 to 624 of the major nuclear protein nucleolin. However, ligand blotting
      experiments with nuclear extracts from U937 and RIN cells showed no binding of
      glycated albumin with nucleolin. The reported amino acid sequences of the 100kDa
      fructosyllysine specific binding protein do not show any homologies with AGE
      receptors. This receptor protein as a nucleolin-like polypeptide belongs to the
      superfamily of RNA-binding proteins.

PMID- 7718616
TI  - Isolation and expression of an Arabidopsis 14-3-3-like protein gene.
AB  - We have isolated an Arabidopsis gene, AFT1, which encodes a 14-3-3-like protein
      (AFT1). The wide distribution of the 14-3-3 protein family in eukaryotes and the
      high steady-state mRNA levels of the AFT1 gene in most tissues throughout
      Arabidopsis growth and development suggest that AFT1 plays an important role(s)
      in Arabidopsis. DNA blot analysis indicates that AFT1 is a single copy gene,
      therefore AFT1 should be a good target for studies involving antisense or sense
      RNA technologies as a means to determine AFT1's function in vivo.

PMID- 7718617
TI  - Cytosolic biosynthesis of GTP and ATP in normal rat pancreatic islets.
AB  - GTP and ATP are necessary for glucose-induced insulin secretion; however, the
      biosynthetic pathways of purine nucleotides have not been studied in pancreatic
      islets. The present work examines the cytosolic pathways of purine nucleotide
      synthesis using intact rat islets cultured overnight in RPMI 1640 medium
      containing either [14C]glycine (to label the de novo pathway) or [3H]hypoxanthine
      (to mark the salvage pathway), with or without mycophenolic acid or L-alanosine
      (selective inhibitors of cytosolic GTP and ATP synthesis, respectively). Addition
      of mycophenolic acid decreased total GTP content (mass) by 73-81%; although the
      incorporation of labeled hypoxanthine into GTP also fell by 87%, the
      incorporation of glycine did not change. Similarly, L-alanosine decreased ATP
      mass by 26-33% in the presence of either label; whereas the incorporation of
      hypoxanthine into ATP fell 59%, the incorporation of glycine was again not
      significantly decreased. Thus, both the de novo and salvage purine nucleotide
      biosynthetic pathways are present in rat islets; however, the salvage pathway
      appears to be quantitatively the more important source of nucleotides. This
      conclusion was supported by additional studies of the effects on nucleotide
      content and insulin secretion of various site-specific inhibitors of purine
      synthesis. These findings have potential relevance to the processes of
      mitogenesis, cell proliferation and differentiation of islet cells, as well as
      for the control of insulin secretion.

PMID- 7718618
TI  - Okadaic acid increased annexin I and induced differentiation of human
      promyelocytic leukemia cells.
AB  - The differentiation of a cell line of human promyelocytic leukemia, HL-60 cells,
      triggered by 12-O-tetradecanoyl 13-phorbol acetate (TPA), depends on the
      phosphorylation of some proteins, such as 17, 27, and 34 kDa proteins, by protein
      kinase C. For elucidation of the mechanism of ligand-induced differentiation of
      HL-60 cells, the effects of okadaic acid (OA), a phosphatase inhibitor, on cell
      differentiation and protein phosphorylation were studied. After treatment with
      OA, HL-60 cells differentiated into macrophage-like cells; within 16 h, 70% or
      more of the treated cells adhered to plastic dishes. The adherent cells did not
      undergo mitosis but began activities such as phagocytosis. OA increased the
      phosphorylation of 17, 23, 27, and 34 kDa proteins, as did TPA. The amount of
      annexin I (39 kDa protein) in HL-60 cells caused to differentiate with OA was 7.5
      fold that without such treatment. Kinetic analysis showed that increased
      transcription of annexin I mRNA caused the increase in annexin I in the
      differentiated cells. Thus, OA and TPA increased cellular levels of annexin I and
      caused the differentiation of HL-60 cells into macrophage-like cells.

PMID- 7718619
TI  - Towards an understanding of the signal transduction pathways for interleukin 1.

PMID- 7718620
TI  - Cytokinins affect spore formation but not cell division in the yeast
      Saccharomyces cerevisiae.
AB  - Cytokinins are N6-substituted adenine derivatives that function as essential
      growth hormones in higher plants. In experimental systems, cytokinins can
      influence cell growth and differentiation among both plant and non-plant tissues.
      The single-celled yeast, Saccharomyces cerevisiae, has served as an effective and
      useful model system for the study of a wide range of cellular phenomena generally
      associated with higher eukaryotes, including mammals. In an attempt to assess the
      efficacy of its use to dissect the molecular basis for plant hormone action, the
      effects of cytokinins on S. cerevisiae with respect to cell division rates and
      sporulation efficiencies were monitored. While none of the cytokinins tested
      influenced mitotic generation times, micromolar concentrations of kinetin
      enhanced the formation of yeast haploid ascospores and even lower concentrations
      of isopentenyladenine inhibited ascus formation.

PMID- 7718621
TI  - Effect of cyclic AMP on urokinase-type plasminogen activator receptor and
      fibrinolytic factors in a human osteoblast-like cell line.
AB  - We investigated the effect of cyclic AMP (cAMP) on the pericellular fibrinolytic
      system in NY cells. Dibutyryl cAMP (dbcAMP) or forskolin increased the level of
      urokinase-type plasminogen activator (u-PA) mRNA and enhanced the secretion of u
      PA antigen into the conditioned medium. These agents also increased u-PA antigen
      on the cell surface. PA inhibitor-1 (PAI-1) antigen was inhibited by dbcAMP or
      forskolin. Butyrate had no effect on the production and secretion of u-PA and PAI
      1. A binding assay of 125I-DFP-u-PA to NY cells revealed a single class of
      binding sites with a Kd of 3.85 nM and Bmax of 0.89.10(5) binding sites/cell. The
      Bmax was increased by dbcAMP (1 mM or 10 mM), forskolin (2 microM or 20 microM)
      of 1.0-, 1.4-, 1.2- and 1.8-fold, respectively. However, the Kd value was not
      changed. Furthermore, the level of mRNA for the u-PA receptor (u-PAR) was
      increased by these agents 1.2-, 1.7-, 1.8- and 2.5-fold, respectively. However,
      butyrate did not alter either the Bmax or the u-PAR mRNA level. These results
      indicated that the pericellular fibrinolytic activity induced by u-PA/u-PAR is
      modulated by cAMP in osteoblast-like cells.

PMID- 7718622
TI  - Expression of fructosyllysine receptors on human monocytes and monocyte-like cell
      lines.
AB  - Short-term exposure of human serum albumin to glucose in vitro results in the
      formation of fructosyllysine residues. Using short-term glucose-modified albumin
      the interactions with human monocytes and with the human monocyte-like cells
      U937, MonoMac 6, HL60, and THP1 were studied. Short-term glycated albumin was
      specifically bound by monocytes, U937 and MonoMac 6 cells, but not by HL60 and
      THP1 cells. This specific binding of short-term glycated albumin was inhibited by
      fructosyllysine, but not by hexitollysine. Short-term glycated albumin did not
      compete for binding of albumin, modified by advanced glycation end products.
      Scatchard analysis of the binding data indicated that there are 10,000 binding
      sites per cell in monocytes or U937 cells and 2000 sites per cell on MonoMac 6
      cells with affinity constants of 9 x 10(6) M-1. Specific binding of short-term
      glycated albumin to human monocytes was observed in 29% of the 101 human subjects
      investigated. Ligand-receptor cross-linking and ligand blotting experiments
      revealed two binding proteins of 100 to 110 and 190 kDa in SDS-PAGE after
      membrane protein solubilization of U937 and MonoMac 6 cells. The binding of short
      term glycated albumin to MonoMac 6 cells induced the production of the cytokines
      IL-1 and TNF.

PMID- 7718623
TI  - Constitutive overexpression of c-fos protein in rat liver epithelial cells
      decreases TGF-beta synthesis and increases TGF-beta 1 receptors.
AB  - We have previously shown that rat liver epithelial cells were more sensitive to
      TGF-beta 1 when they were transfected with c-fos cDNA. We analyzed the production
      of TGF-beta and TGF-beta 1 binding proteins in transfected and parental cells.
      TGF-beta-like activity released in the medium was reduced in c-fos expressing
      cells. TGF-beta 1 binding sites were more numerous in transfected cells (x3).
      Cross-linking studies confirmed that c-fos transfected cells showed increased
      binding of 125I-TGF-beta 1 to membrane binding sites corresponding to type I, II
      and III receptors. Transfected cells internalized and degraded 125I-TGF-beta 1
      more rapidly than parental cells. TGF-beta 1 incubation rapidly down-regulated
      the receptors. In parental cells, the down-regulation was total, while in
      transfected cells, a few binding proteins could still be detected. The c-fos cell
      line is an interesting tool in analysing the mechanism of action of TGF-beta.

PMID- 7718624
TI  - Catalytic subunits of the porcine and rat 5'-AMP-activated protein kinase are
      members of the SNF1 protein kinase family.
AB  - The 5'-AMP-activated protein kinase (AMPK) regulates the fatty acid and sterol
      synthesizing pathways via phosphorylation of acetyl-CoA carboxylase and HMG-CoA
      reductase, respectively. Highly purified kinase from porcine liver contains three
      apparent subunits of molecular mass 63 kDa, 40 kDa and 38 kDa. Peptide sequencing
      of the 63 kDa protein (AMPK63cat) revealed that this polypeptide is the catalytic
      subunit of the kinase. Porcine peptide sequences were used to clone by RT-PCR
      partial length cDNAs for the catalytic domains of the porcine AMPK63cat, and its
      rat homolog, which were virtually identical in deduced amino acid sequence.
      Screening of a rat liver cDNA library with these partial length cDNAs and with
      degenerate oligonucleotides yielded several unique clones, some of which had a
      142 bp deletion in the catalytic domain of the kinase. A consensus full-length
      sequence with a 1.7 kb open reading frame has been constructed from overlapping
      library and PCR-derived clones. A large mRNA for rat AMPK63cat (8.5 kb) is
      expressed in nearly all rat tissues, with highest levels detectable in heart and
      skeletal muscle. Using PCR, the presence of two mRNA species with or without the
      142 bp deletion in the catalytic domain was noted in all rat tissues examined.
      Comparison of the deduced protein sequence of AMPK63cat reveals highly conserved
      homologies in both the catalytic and non-catalytic domains to several members of
      the SNF1 kinase family, including kinases from Arabidopsis, barley, rye, and S.
      cerevesiae, as well as to other mammalian kinases and to a C. elegans kinase. The
      high evolutionary conservation of both kinase structure and function (metabolite
      sensing) coupled with their pattern of tissue/organism expression suggest that
      the mammalian members of this kinase family likely play wider roles than the
      regulation of cellular lipid metabolism.

PMID- 7718625
TI  - Modulation of the receptor binding affinity of amphiregulin by modification of
      its carboxyl terminal tail.
AB  - Amphiregulin (AR), a heparin-binding, epidermal growth factor (EGF) receptor
      ligand has homology with EGF but exhibits a lower affinity for the EGF receptor
      than EGF. As the mature form of AR is truncated at the C terminus and lacks a
      conserved leucine residue known to be essential for high affinity binding of EGF
      to the EGF receptor, wild-type AR (AR1-84), a C-terminally extended AR construct
      incorporating six residues from the predicted coding sequence of AR (AR1-90) and
      a similarly extended construct with a Met86 to Leu substitution (AR1-90(leu86))
      were expressed as recombinant proteins in yeast, purified by heparin affinity and
      C18 reverse phase chromatography and their relative biological activities
      determined. The growth factors were tested in mitogenesis and EGF receptor
      autophosphorylation assays and their relative order of potencies was found to be
      leu86 > met86 > wt. The AR1-90(leu86) construct was found to be 50- to 100-fold
      more active than wild type AR1-84 consistent with previously reported studies of
      the role of the equivalent C-terminal leucine in EGF or TGF alpha. Significantly,
      the C-terminally extended form of AR, AR1-90, which utilized six residues from
      the predicted coding sequence, was 10-times more active than wild type AR1-84.
      This difference in activity of the C-terminally extended form of AR may be of
      biological significance since differential proteolytic processing of the AR
      precursor in vivo could result in production of multiple forms of the growth
      factor with differing affinities for the EGF receptor and hence differing
      biological potencies.

PMID- 7718626
TI  - Reduction in platelet-derived growth factor receptor mRNA in v-src-transformed
      fibroblasts.
AB  - The status of the platelet-derived growth factor (PDGF) receptor in normal rat
      kidney (NRK) fibroblasts and in NRK fibroblasts transformed by the v-src oncogene
      or the polyoma middle T (pmt) antigen has been compared. v-src-NRK cells have 7
      fold fewer surface binding sites for PDGF than NRK cells, but the affinity of the
      residual receptors for PDGF is reduced only 2-fold. Levels of the PDGF receptor
      measured by Western blotting or in an autophosphorylation assay in vitro are 8-
      and 4-fold lower respectively in v-src-NRK cells than in NRK cells. No PDGF
      induced phosphorylation of the PDGF receptor is apparent after 32P-labelling of
      intact v-src-NRK cells, implying that the reduction in PDGF receptor levels is
      not a consequence of production of autocrine PDGF. A 10-fold reduction in the
      amount of mRNA for the PDGF receptor is also observed in v-src-NRK cells. No
      decrease in PDGF receptor protein or mRNA levels is observed in pmt-NRK cells. We
      conclude that levels of the PDGF receptor in v-src-transformed NRK fibroblasts
      are modulated by reduction in the level of PDGF receptor mRNA.

PMID- 7718627
TI  - Differential regulation of primary response gene expression in skeletal muscle
      cells through multiple signal transduction pathways.
AB  - One of the earliest cellular responses to growth factors is the rapid induction
      of primary response genes. One group of such genes was originally isolated as
      tetradecanoyl phorbol acetate (TPA) inducible sequences (TIS genes) from mouse
      3T3 cells. Proteins encoded by the TIS genes include two transcription factors:
      TIS8 (also known as egr1/NGFIA/zif268) and TIS1 (also known as NGFIB/nur77/N10).
      We have examined the inducibility of these two genes in a skeletal muscle cell
      line in response to agents that have been reported to block muscle
      differentiation. We report here that basic fibroblast growth factor (bFGF)
      induced the expression of both TIS1 and TIS8 in mouse C2C12cells. Both genes were
      also inducible by TPA while forskolin which activates the cAMP-dependent pathway
      induced TIS1 but not TIS8. Down-regulation of protein kinase C (PKC) activity by
      TPA pretreatment repressed the bFGF induction of TIS1 but had little effect on
      the bFGF-stimulated expression of TIS8. Moreover, while both TPA and bFGF
      stimulated the hyperphosphorylation of c-RAF and the activity of MAP kinase, TPA
      pretreatment failed to block RAF phosphorylation or the stimulation of MAP kinase
      activity by bFGF. Induction of the two TIS genes in skeletal myoblasts therefore
      appeared to be dependent to different extents on the activation of protein kinase
      A (PKA), PKC and MAP kinase.

PMID- 7718628
TI  - Advances in biopharmaceutical analysis in the People's Republic of China: 1991
      1993.
AB  - The methodological studies on biopharmaceutical analysis of drugs and their
      metabolites by liquid and gas chromatography with various detectors have been
      reviewed. Research articles were selected from well known journals published in
      the People's Republic of China between January 1991 and March 1993. The
      applications of these methods in bioavailability, pharmacokinetics, therapeutic
      drug monitoring and metabolic studies have also been discussed.

PMID- 7718629
TI  - Analysis of basic antimalarial drugs by CZE; Part 2. Validation and application
      to bioanalysis.
AB  - This report describes some of the quantitative aspects of the CZE separation of
      proguanil, chloroquine and their respective metabolites, the separations of
      which, by CE and MEKC, were reported in Part 1. Results obtained on the precision
      of migration time and peak areas using the alternative injection methods of
      vacuum and electrokinetic are described and discussed. The increase in
      concentration sensitivity using electrokinetic injection with an organic
      injection solvent reported in Part 1 is confirmed and the resultant limits of
      detection in urine reported. An assay method for these compounds in urine is
      described which incorporates a pretreatment stage of solid phase extraction and
      the main analytical parameters used in the validation of such an assay are
      reported. The limitation of the sample pretreatment used when applied to matrices
      of plasma and saliva are reported and discussed in the context of the
      electrokinetic injection method used.

PMID- 7718630
TI  - Analysis of unconjugated morphine, codeine, normorphine and morphine as
      glucuronides in small volumes of plasma from children.
AB  - A sensitive method for the analysis of unconjugated morphine, codeine,
      normorphine and total morphine after hydrolysis of glucuronide conjugates is
      described. The method was applicable to 50-microliters volumes of plasma. The
      analytes were converted to heptafluorobutyryl (HFB) derivatives before analysis
      by gas chromatography-negative ion chemical ionization mass spectrometry.
      Morphine and codeine were quantified against their [2H3]-isotopomers. Linearity,
      precision and accuracy were quite acceptable (in the 10(-10)-10(-9) g range), and
      the absolute limits of detection were < 1 pg.

PMID- 7718631
TI  - Validation of a capillary electrophoresis method for the determination of
      potassium counter-ion levels in an acidic drug salt.
AB  - This paper describes the first report of the validation of a capillary
      electrophoresis method for the quantitative determination of potassium levels in
      the potassium salt of an acidic drug. Validation criteria include precision,
      linearity, robustness and repeatability. The use of an internal standard enabled
      precision values of < 1% RSD to be obtained for peak area ratios. Careful control
      of capillary conditioning and temperature enabled migration time precisions of <
      0.5% RSD. Results obtained by this method were in agreement with those generated
      by ion exchange chromatography and the theoretical potassium content of samples
      tested. Features of the method, compared to alternative analytical techniques,
      include simplicity, speed and accuracy. The method is now in routine use within
      our laboratories.

PMID- 7718632
TI  - Utilizing nuclear magnetic resonance (NMR) spectroscopy for assessing nadolol
      racemate composition.
AB  - NMR methods were developed for the determination of the racemate composition in
      nadolol raw materials. With high-field instruments (400 MHz or greater) the
      racemate ratio may be determined by the relative heights of the t-butyl peaks,
      which are well enough resolved for this determination. For lower field
      spectrometers, the t-butyl peaks are not resolved. An NMR method has been
      developed which involves preparation of the tribenzoate derivative of the drug.
      Seven lots of nadolol raw material, as well as several standards, were analysed
      for their racemate content. Three lots of raw material did not meet the USP
      limits of 40-60% for racemate A. Of these, two were granular in appearance and
      were found to vary markedly in racemate composition in successive analyses. The
      results for all the materials of uniform content agree very well with those from
      the HPLC method, as well as for the USP IR method using the absorbance at the
      corrected wavelength.

PMID- 7718633
TI  - Determination of the enantiomer of a cholesterol-lowering drug by cyclodextrin
      modified micellar electrokinetic chromatography.
AB  - The development, optimization and application of a chiral CE (capillary
      electrophoresis) method for the determination of the enantiomer content of a new
      cholesterol-lowering drug (BMS-180431-09) is discussed. The chiral CE technique,
      cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC), was
      employed with hydroxypropyl beta-cyclodextrin as the chiral selector in the run
      buffer. The detection limit of the unwanted enantiomer was about 0.06% w/w. The
      effect of various parameters on the separation, validation data and examples of
      the application of the chiral CE method are included.

PMID- 7718634
TI  - Spectrophotometric determination of flunarizine dihydrochloride through the
      formation of charge-transfer complex with iodine.
AB  - A spectrophotometric method is described for the assay of flunarizine
      dihydrochloride. The method is based on the molecular interaction between the
      drug and iodine, to form a charge-transfer complex in which the drug acts as n
      donor and iodine as sigma-acceptor. The iodine was found to form charge-transfer
      complex in a 1:1 stoichiometry with absorption bands at 295 and 355 nm. The
      concentrations were linear over 8-13 micrograms ml-1 at both 295 and 355 nm,
      respectively. A complete, detailed investigation of the formed complex was made
      with respect to its composition, associated constant and free energy change. The
      method has been applied successfully to the analysis of commercially available
      flunarizine dihydrochloride capsules without interference from the capsules
      excipient. To validate the proposed method, its accuracy and precision, the
      results were statistically compared with a newly developed reversed-phase HPLC
      procedure using Student-t and F-ratio tests.

PMID- 7718636
TI  - HDL subfractions as altered in cancer patients.
AB  - Previous studies from the authors' laboratories have shown that cancer patients
      are characterized by lower levels of high-density lipoprotein cholesterol (HDL-C)
      compared with those of normal subjects. HDLs are a complex class of lipoproteins
      which can be divided mainly into two categories, HDL2 and HDL3, that have not
      only different lipid and protein composition but also different functions.
      Therefore, for a better understanding of the metabolism of HDL during tumour
      growth, the different subfractions of HDL (HDL2 and HDL3) were analysed in the
      serum of neoplastic patients using a rapid and simple high-performance liquid
      chromatography (HPLC) method for the analysis. The results obtained showed that
      serum from neoplastic patients exhibits a peculiar pattern in the distribution of
      HDL subfractions, consisting of a sharp decrease in HDL3 and a consequent
      increase of the normal HDL2/HDL3 ratio. It is suggested that evaluation of the
      HDL subfractions may be of clinical relevance for cancer status and that due to
      its simplicity, short analytical time and small sample volume required, the HPLC
      technique used in this study can be easily applied to routine analysis in cancer
      patients.

PMID- 7718635
TI  - A supercritical fluid chromatographic method using packed columns for
      phenylbutazone and oxyphenbutazone in serum, and for phenylbutazone in a dosage
      form.
AB  - The separation of phenylbutazone (PB) and its major metabolite oxyphenbutazone
      (OPB) using supercritical fluid chromatography (SFC) has been investigated. The
      separations were studied on octadecylsilane, silica and cyano packed columns with
      5% methanol in carbon dioxide as mobile phase and detection at 240 nm. The
      octadecylsilane column showed the most favourable chromatographic parameters for
      the analysis of the analytes. Recoveries of PB and OPB from spiked human serum
      were in the 82-83% range using solid phase extraction on an ODS cartridge. Limits
      of detection of the SFC assay were 0.1 microgram ml-1 for PB and 1.0 microgram ml
      1 for OPB. Accuracy and precision of the method were in the 0.24-4.94% range for
      PB and OPB. The SFC method was directly comparable to an HPLC assay of the same
      analytes. The SFC method was also applied to a commercial 100 mg dosage form of
      PB with good recovery of PB.

PMID- 7718637
TI  - Quantitative determination of CaCO3 and glycine in antacid tablets by Laser Raman
      Spectroscopy.

PMID- 7718638
TI  - Gas-liquid chromatographic quantitation of polyethylene glycol 400 in
      pharmaceutical preparations.

PMID- 7718639
TI  - Chiral LC of a cholesterol-lowering drug using serum albumin mobile phases.

PMID- 7718640
TI  - Biotherapy of chronic myelogenous leukemia.
AB  - The aim of this review is to summarize the current knowledge on the clinical
      results of biotherapy of chronic myelogenous leukemia (CML) and potential
      mechanisms of the antitumor action of interferon alpha. IFN alpha treatment
      induces hematologic and cytogenetic remissions in patients with chronic phase
      CML. In addition, the duration of the chronic phase is prolonged by IFN alpha
      resulting in a significant survival benefit. In two randomized clinical trials
      this survival benefit was demonstrated in all chronic phase CML patients
      independent of their risk scores. Moreover, IFN treatment also delays the onset
      of clinical relapse after allogeneic bone marrow transplantation. The critical
      mechanisms of IFN action have not yet been identified. Both direct and indirect
      antiproliferative mechanisms have been described. In particular, differential
      regulation of growth promoting and growth inhibiting cytokines represents an
      attractive hypothetical mechanism of IFN action. Nevertheless, no leukemia
      specific IFN activities explaining cytogenetic remissions and/or delay of disease
      progression have been identified. Further research on that field are required to
      further improve biological CML therapies.

PMID- 7718641
TI  - P53 tumor suppressor gene in chronic myelogenous leukemia: a sequential study.
AB  - Loss of the p53 gene alleles was investigated in 26 patients with Ph+, BCR/ABL+
      chronic myeloid leukemia (CML) by means of the polymerase chain reaction and
      restriction fragment length polymorphism (PCR-RFLP) analysis using the
      restriction enzyme AccII. In all cases, peripheral blood and/or bone marrow
      samples were obtained at different times during the chronic phase of the disease
      and at blast crisis, and in some of them also at the accelerated phase. Of the 12
      cases considered informative, 11 evolved into myeloid type blast crisis and one
      into a lymphoid blast crisis, whereas only two showed an i(17q) chromosome at
      cytogenetic study. In four of the 12 informative cases, a loss of one p53 gene
      allele was observed, in all cases coincident with the development of the
      accelerated phase or blast crisis. One patient with a deleted p53 gene allele, in
      whom it was possible to analyze the gene structure in the three CML evolutive
      phases (chronic and accelerated phases and blast crisis), showed loss of the p53
      gene allele in both the accelerated and the blastic phase, but not during the
      chronic phase. On the other hand, one of the two cases with an i(17q) chromosome
      exhibited one allelic deletion of the p53 gene. Thus, the relatively frequent
      monoallelic deletion of the p53 gene coincident with the appearance of the blast
      crisis registered in the present study would support a possible role of the p53
      gene alterations in the evolution of CML to its final stages.

PMID- 7718642
TI  - Pulmonary fungal infections in patients with hematological malignancies-
      diagnostic approaches.
AB  - In a retrospective study of 56 patients with hematological malignancies and
      fungal pneumonia we have analyzed the value of different diagnostic procedures.
      In all patients (Candida n = 29, Aspergillus n = 23, mixed fungal infection n =
      4) bronchoscopy and/or high-resolution computed tomography of the lungs was
      performed. Cultural detection of fungi in bronchoalveolar lavage was successful
      in 23/32 Candida and 11/23 Aspergillus pneumonias. Other relevant pathogens were
      identified by bronchoscopy in 21 cases. Thorax CT scans showed diagnostic
      evidence of fungal pneumonia in 10/13 Candida and in 16/18 Aspergillus
      infections. Blood cultures were positive in 9/33 Candida pneumonias and in none
      of aspergillosis cases. Serological testing and surveillance cultures had only
      limited value for the early diagnosis of pulmonary mycosis. Our data suggest that
      bronchoscopy and high resolution CT scans are mutually complementary diagnostic
      tools with high sensitivity in patients with hematological malignancies and new
      pulmonary infiltrates. These procedures facilitate the early and reliable
      recognition of invasive fungal disease which may have a bearing on the
      initiation, length, and differential therapy of antimycotic drugs.

PMID- 7718643
TI  - Presenting signs and symptoms in multiple myeloma: high percentages of stage III
      among patients without apparent myeloma-associated symptoms.
AB  - We studied the medical histories of 127 patients diagnosed with multiple myeloma
      included in a population-based registry of 945 patients with a para-protein or
      multiple myeloma in the region of the Comprehensive Cancer Center West (CCCW). We
      defined patients "not immediately diagnosed" or "delayed diagnosis" as those
      patients in whom myeloma was not included in the initial differential diagnosis.
      We found that 37% belonged to this category. These patients more often had
      symptoms not associated with multiple myeloma. Since a surprising 51% of patients
      with delayed diagnosis turned out to have stage-III myeloma, the physician should
      be alert to the presence of this disease, despite the fact that co-morbidity may
      mask its presence.

PMID- 7718644
TI  - Lactate dehydrogenase-release assay: a reliable, nonradioactive technique for
      analysis of cytotoxic lymphocyte-mediated lytic activity against blasts from
      acute myelocytic leukemia.
AB  - Treatment of patients in remission of acute myelocytic leukemia using
      immunotherapy with interleukin 2 is a new approach to prolonging remission
      duration in this disease. As an important mechanism for the pathophysiology of
      eradication of residual myelocytic blast populations, activation of cytotoxic
      effector lymphocytes has frequently been discussed. However, the associated
      immunological research has been complicated to some extent, because in
      conventional chromium 51-release assays, blast cells frequently fail to
      incorporate sufficient amounts of 51Cr and/or spontaneously release high amounts
      of 51Cr. Recently, we established a culture system which promotes the outgrowth
      of cytotoxic T lymphocytes in bone marrow-derived mononuclear cells cultured in
      IL-2. To study cytotoxicity and the responsible mechanisms of the obtained T-cell
      lines and clones, we modified a previously described cytotoxicity assay, based on
      the release of lactate dehydrogenase (LDH-release assay) for use in cryopreserved
      blasts obtained from the bone marrow of patients with acute myelocytic leukemia.
      Using this assay, we were able to detect cytotoxicity of IL-2-activated
      peripheral blood lymphocytes from three healthy controls against a number of
      blast samples obtained from the bone marrow of patients with AML (up to more than
      40% lysis at an effector target cell ratio of 20:1). However, a minority of AML
      blasts seem to be resistant to lysis by IL-2-activated lymphocytes. In bone
      marrow-derived T-cell lines from patients with AML we detected lytic activity
      against autologous blasts in three of seven cases tested by LDH release, ranging
      from 29 to 63% at an effector target ratio of 10:1. Additionally, T-cell clones
      with different phenotypes were established which were able to mediate
      cytotoxicity against autologous blast cells. Thus, cytotoxicity against freshly
      isolated blasts from patients with acute myelocytic leukemia can be analyzed
      reliably, reproducibly, and without the use of isotopes by the LDH-release assay.

PMID- 7718645
TI  - Erroneously low APC ratio in patients with lupus anticoagulant.

PMID- 7718646
TI  - Improving our self-episteme.

PMID- 7718647
TI  - How viable is Victoria's funding policy?

PMID- 7718648
TI  - Public health and national health policy.

PMID- 7718649
TI  - Illnesses that Australians most feared in 1986 and 1993.
AB  - This study identified illnesses Australians most feared getting, and determined
      whether there had been any changes between 1986 and 1993. An open-ended question
      about illnesses was embedded in an omnibus face-to-face survey of representative
      samples of Australians (1986, n = 1213; 1993, n = 1268). Cancer was by far the
      most feared illness, with over 60 per cent of first mentions and around 80 per
      cent of first or second mentions. Acquired immunodeficiency syndrome (AIDS) and
      heart disease were the only other illnesses mentioned by more than 10 per cent of
      the sample as the first or second most feared illness. There were no differences
      across time in first mentions of these illnesses, but cancer had more mentions
      overall in 1993. Concern about cancer may have increased over the seven years.
      Mentions of dementia and blindness also increased across the two surveys.

PMID- 7718650
TI  - Purchaser/provider separation and managed competition: reform options for
      Australia's health system.
AB  - A purchaser/provider separation and managed competition have been recommended as
      options for reform of Australia's health system. This paper presents the
      theoretical basis and supposed advantages of each model. The introduction of the
      purchaser/provider separation in the United Kingdom and New Zealand is described,
      as are the proposals for implementation of managed competition in the United
      States and the Netherlands. The potential for either model to deliver its
      promised benefits is critically evaluated in the light of existing evidence. As
      yet neither model can command unqualified support but both are worthy of further
      consideration.

PMID- 7718651
TI  - Hospital inpatient costs resulting from road crashes in Western Australia.
AB  - The purpose of this study was to estimate the inpatient costs of road crashes in
      Western Australia, and to investigate factors relating to casualties and their
      injuries that affect the hospital costs resulting from road crashes. All road
      crash casualties who were injured severely enough to be hospitalised in Western
      Australia in 1988 were included. A casemix classification system was used to
      classify patients into diagnostic related groups. Hospital costs were assigned to
      individual patients on the basis of their diagnostic related group and length of
      hospital stay. The annual cost of hospital treatment for road crash casualties
      was estimated as $13.9 million, and 33 per cent of this was incurred by those
      with lower extremity injuries and 27 per cent by those with head injuries.
      Hospital costs per casualty ranged from an average of $1388 for those sustaining
      minor (Abbreviated Injury Scale severity score of 1 or 2) spinal injuries to
      $16,580 and $33,424, respectively, for those sustaining severe (Abbreviated
      Injury Scale severity score of 4 or 5) head and spinal injuries. A multivariate
      analysis of variance revealed the following factors as having a significant
      independent effect on the hospital inpatient costs of road crash casualties: type
      of hospital (teaching or nonteaching), body region of injury, injury severity
      level and road user group. There were also significant interaction effects
      between different factors. Since hospital inpatient costs vary considerably
      across factors, using average cost data in the specific economic evaluation of
      road safety interventions for groups of road users is inappropriate.

PMID- 7718652
TI  - Will early detection of breast cancer reduce the costs of treatment?
AB  - A substantial investment in resources is required to provide a population-based
      mammography screening program. At the same time, screening may also reduce the
      costs of treating breast cancer. Empirical evidence to support such cost savings,
      however, is limited. This paper presents a simulation of the impact on treatment
      costs of a population-based mammography screening program in New South Wales. A
      1991 cohort of women aged 45 to 69 years is followed for the period 1991 to 2023.
      With two-yearly screening, the present value of the total health service costs
      for this cohort would be approximately $112 million. Primary treatment, at $60
      million, would cost $5 million more with screening than without. Treatment for
      advanced stages of the disease would cost $22 million less. Overall, this
      analysis suggests that savings in treatment costs are relatively small in
      relation to the overall resource requirements of organised screening.

PMID- 7718653
TI  - An economic analysis of alternatives for childhood immunisation against
      Haemophilus influenzae type b disease.
AB  - Cost-effectiveness and cost-utility analyses of immunisation strategies against
      invasive Haemophilus influenzae type b (Hib) disease in Australia were based on a
      hypothetical birth cohort of 250,000 non-Aboriginal Australian children. The
      model predicted that, without immunisation, 625 cases of invasive Hib disease
      would occur in under-five-year-olds, with direct costs of $10.2 million.
      Universal public sector vaccination beginning before six months of age (6MVAC)
      prevented 80 per cent of cases; vaccination at 12 months (12MVAC) 62 per cent and
      at 18 months (18MVAC) 46 per cent. At a vaccine cost of $15 per dose, 18MVAC gave
      the lowest cost per quality-adjusted life year (QALY) over a wide range of model
      assumptions, with 6MVAC the 'best' alternative. The best estimate ($ per QALY)
      for 6MVAC was $6930 (three doses), for 12MVAC $9136 (two doses) and for 18MVAC
      $1231 (one dose). The cost per QALY of single dose catch-up immunisation of older
      children was estimated at $8630 at two years, $27,000 at three years and $117,000
      at four years if done at a scheduled visit; these values were increased if an
      additional medical visit was included. The threshold cost per vaccine dose at
      which an immunisation program became cost-saving was estimated for 6MVAC, 12MVAC
      and 18MVAC as $11, $10 and $14. Even under a worst-case scenario, an immunisation
      program at 6, 12 or 18 months became cost-saving if indirect costs of death were
      included. Comparison with previous analyses revealed the importance of the
      incidence and age distribution of disability and assumptions about vaccine
      administration costs in determining model outcomes.

PMID- 7718654
TI  - Who has Pap smears in New South Wales? Patterns of screening across
      sociodemographic groups.
AB  - The aim of this study was to determine whether Pap smear screening at adequate
      intervals is associated with area of residence, frequency of consultations with a
      general practitioner, socioeconomic status and non-English-speaking background. A
      representative 10 per cent sample of women from New South Wales and the
      Australian Capital Territory, aged 25 to 69 years and registered with the Health
      Insurance Commission (Medicare) (N = 155,281) was used to obtain age, postcode,
      frequency of Pap smears and frequency of consultations with general practitioners
      in the three-year period from February 1985 to January 1988. Census data for each
      postcode area were used as an indicator of other socio-demographic
      characteristics. Age-specific screening rates did not vary between Sydney,
      Newcastle/Wollongong, Canberra, and nonmetropolitan areas. In all age groups,
      having had a smear was most strongly associated with the frequency with which a
      woman consulted a general practitioner. Women who visited a general practitioner
      at least four times a year on average were about twice as likely to have had a
      recent Pap smear as those who averaged less than one visit per year. Screening
      rates were lowest among women living in areas with the most non-English-speakers
      and the lowest socio-economic status. Sociodemographic factors and health service
      usage patterns influence the proportion of women who are currently being
      screened. Evaluation of interventions to improve Pap smear screening rates should
      consider whether the percentage of women screened increases overall, and also
      whether the imbalances in screening rates between different groups are
      diminishing.

PMID- 7718655
TI  - Weight-loss strategies and beliefs in high and low socioeconomic areas of
      Melbourne.
AB  - Overweight is a serious health risk and is prevalent in Australia. This study
      explored sex, socio-economic status and age differences in body mass index, the
      perceived effectiveness of weight-loss strategies and the frequency of their use,
      and awareness of the risks of obesity in a random sample of adult men (n = 457)
      and women (n = 537) from higher and lower socioeconomic areas. According to self
      reports, 37 per cent of the sample were overweight or obese. More men than women,
      and more older than younger respondents, were overweight. There were no sex
      differences in the frequency of obesity. There were significantly more obese
      individuals in the lower than in the higher socioeconomic area. Women more
      frequently put themselves in a higher weight category while men more frequently
      put themselves in a lower weight category. Fifty-eight per cent of respondents
      reported the desire to lose weight and 24 per cent of the sample were trying to
      lose weight on the survey day; 46.9 per cent had attempted to lose weight in the
      previous 12 months, and these were more likely to be female, younger and obese or
      overweight. Only minor differences according to sex or socioeconomic status were
      found in beliefs about the effectiveness of different weight-loss strategies.
      However, older respondents were less likely to have exercised recently as a means
      of weight reduction. There was good recognition of diseases made worse by being
      overweight, although the health risk of male fat distribution patterns was not
      widely known.

PMID- 7718656
TI  - Skin cancer prevention: a link between primary prevention and early detection?
AB  - The aim of this paper was to determine if there is any link between primary
      prevention and early detection for skin cancer. Results from a study of a large
      random sample of Gold Coast residents (N = 995) identified an association (P <
      0.01) between individual primary prevention and early detection activities.
      People were also more likely to use both prevention methods if they had personal
      experience with skin cancer (P = 0.01) or if they were male (P = 0.05). Future
      primary prevention and early detection skin cancer programs might be most
      effective if they are combined.

PMID- 7718657
TI  - Enhancing the early detection of melanoma within current guidelines.
AB  - Queensland has the highest reported incidence of malignant melanoma in the world,
      and early detection offers the possibility of reducing the burden of this cancer
      in the short term. We report on a survey of 995 residents of the Gold Coast,
      Queensland, regarding behavioural aspects of the early detection of skin cancer.
      Survey results suggest that although many people report some form of skin
      examination behaviour, by either checking their own skin, having another
      nonmedical person check their skin, or by going to their general practitioner for
      a skin check, much of this activity may be inadequate. They indicate that current
      early detection could be enhanced by encouraging individuals and general
      practitioners to extend the coverage of the examinations they already conduct.

PMID- 7718658
TI  - True believers? Characteristics of general practitioners in Victorian community
      health centres.
AB  - General practitioners have been part of multidisciplinary services in Victoria
      Community Health Centres (CHCs) for 20 years. This model institutionalizes a high
      degree of integration between general practitioners and other primary care and
      community service personnel. Of 51 eligible full-time general practitioners in
      Victorian CHCs, 46 were interviewed, using a structured questionnaire. General
      practitioners in CHCs were younger, less experienced and more likely to be female
      than other general practitioners. Nearly three-quarters were salaried. The
      philosophy of practice and the conditions of employment were the commonest
      reasons for entering CHC practice. Teamwork and the conditions of employment were
      felt to be the biggest advantages of CHC practice, while difficulties with
      management and the perceived loss of professional ownership and control were the
      commonest disadvantages. None reported interference from the CHC management in
      their clinical practice. Nearly a quarter of full-time CHC general practitioners
      do not undertake any formal community health promotion activities. Forty-five per
      cent of respondents intended to leave their CHC within the next five years.
      Universal health insurance has diminished the impact of CHC general practice. The
      philosophy of CHCs and the salaried nature of the employment continues to attract
      general practitioners. High staff turnover is a feature of CHC general practice,
      in part related to young doctors making an initial, but not long-term commitment
      to CHC practice. However, the loss of professional control and management
      difficulties should be addressed, as these may contribute to the high turnover.

PMID- 7718659
TI  - Assessment of self-report in HIV surveillance: a pilot study.
AB  - The basis of HIV exposure category classification was investigated among selected
      cases of newly diagnosed HIV infection. Questionnaires seeking specific
      information on patient-reported exposure to HIV were forwarded to doctors who had
      requested the HIV antibody test for patients who met the study sample criteria.
      The cases of interest were those newly diagnosed between 1 January and 31 October
      1991 and notified to state and territory health authorities as having been
      attributed to exposures to HIV other than male homosexual contact or receipt of
      blood, blood products or tissue. A total of 158 questionnaires was forwarded and
      59 per cent were returned. Among the returned questionnaires included in the
      study sample, exposure to HIV on the original notification to the health
      authority was given as injecting drug use (8 per cent, 3 of 37), heterosexual
      contact (46 per cent, 17 of 37), or unavailable (46 per cent, 17 of 37). A clear
      basis for HIV exposure category classification was provided on the questionnaires
      for 70 per cent (7 of 10) of cases among women, whereas among men whose infection
      was attributed to heterosexual contact, a basis for exposure category
      classification was specified for only 43 per cent (10 of 23) of cases. Although
      the study was limited by the low response rate, use of the questionnaire provided
      a relatively simple means for assessing self-reported HIV exposure history.

PMID- 7718660
TI  - The impact of caring upon the health of older women.
AB  - Much community care relies upon the provision of unpaid care by family members.
      The short- and longer-term effects of providing care upon older women were
      researched in an interview survey of 286 women aged over 50 in urban and rural
      areas of Queensland. The findings were validated by reports from the women's
      general practitioners. The results suggest that providing care has both short-
      and long-term negative effects upon the physical health and emotional wellbeing
      of older women. The major predictor of a range of self-reported health problems
      was the level of self-reported stress. Implications are drawn for both community
      care policy, which needs to focus upon the impact on the carer of continuing to
      provide care at home, and for health research relating to older women, which has
      ignored the demands of caring among older people.

PMID- 7718661
TI  - Cardiovascular risk factors in South Australians with diabetes.
AB  - This study ascertained the prevalence of diabetes and compared the prevalence of
      cardiovascular risk factors among people with and without diabetes. Data were
      collected as part of the South Australian Health Omnibus Survey which involved a
      representative population sample of 6398 adults in metropolitan and country South
      Australia who were interviewed in their own homes. The self-reported prevalence
      of diabetes was found to be 3 per cent overall. This varied from approximately 1
      per cent in the 15- to 39-year age group to 10.5 per cent in people aged over 80
      years. Those with diabetes had a higher prevalence of cardiovascular risk factors
      than those without diabetes. There is a need for improved vigilance with people
      who have diabetes and interventions to modify the risk factors associated with
      cardiovascular disease.

PMID- 7718662
TI  - Prostate cancer screening and men's health.

PMID- 7718663
TI  - Prevention issues at the Tenth International Conference on AIDS.

PMID- 7718664
TI  - General practitioners' estimates of the ideal benign-to-malignant ratio for
      excised pigmented lesions.

PMID- 7718665
TI  - [Lectins in the study of the carbohydrate part of glycoproteins and other native
      glycoconjugates].
AB  - The applications of lectins (mostly lectin sorbents) combined with other
      carbohydrate-binding proteins to the study of glycoproteins and their
      oligosaccharides or glycopeptides are reviewed. Data on the
      oligosaccharide/glycopeptide specificity of lectins and their interaction
      (sensitivity) with (to) relatively rarely used sugars and their derivatives are
      presented.

PMID- 7718666
TI  - [Allergens from Dermatophagoides dust mites: origin, antigenic and structural
      characteristics, and therapeutic agents].
AB  - Micromites (genus Dermatophagoides) are the major source of allergens in house
      dust. Four homologous classes of major allergens have been isolated from extracts
      of D. pteronyssinus and D. farinae mites. According to current theories, all
      major mite allergens are proteins of gastrointestinal origin. Group I mite
      allergens, Der pI and Der fI, are thermolabile glycoproteins with M(r) of 25 kDa.
      A comparison of primary structure of these proteins reveals a 30% homology with
      cathepsins B and H, papain and actinidine. Analysis of enzymatic activities
      reveals that group I allergens are proteolytic enzymes related to the class of
      cysteine proteinases. With regard to antigenic composition, Der pI and Der fI
      have three common and two species-specific epitopes. The amino acid sequence of
      the major allergenic determinant for Der pI has been established. Group II mite
      allergens, Der pII and Der fII, are single-chain thermostable proteins with M(r)
      of 10-14 kDa and are said to bear many common features with the lysozyme. Group
      III mite allergens are analogous to trypsin. A 50% homology of amino acid
      sequences of Der pIII and Der fIII to those of vertebrate and invertebrate serine
      proteinases has been found. To the fourth group of major mite allergens one may
      relate mite amylase (M(r) = 56-60 kDa). A high degree of homology has been
      established between group IV allergens and mammalian alpha-amylase. Mite
      allergens of all groups induce the production of specific IgE antibodies in human
      organism. The use of purified allergens increases the efficiency of diagnosis and
      treatment of mite-induced allergoses. Modified forms of mite allergens
      (allergoids, allergens adsorbed on carriers, liposome preparations, etc.) are
      helpful tools in specific immunotherapy.

PMID- 7718667
TI  - [Mechanisms of allogenic recognition in transplantation systems].
AB  - Transplantation of organs, tissues or cells triggers in the organism an immune
      response to foreign (allogenic) proteins of the donor's Major Histocompatibility
      Complex, eventually resulting in graft rejection. The crucial role in the
      allogenic immune response belongs to T-lymphocytes. The structure of allogenic
      targets recognized by alloreactive T-lymphocytes is still open to question. The
      current state of knowledge concerning allorecognition is reviewed with special
      reference to the type (direct or indirect) of T-cell recognition of alloantigens
      and their roles in graft rejection. Special attention is given to the
      contribution of peptides to allogenic targets formation and the role of tolerance
      in transplantation systems.

PMID- 7718668
TI  - [Purification and characteristics of AMP-deaminase from trout white muscle].
AB  - AMP-deaminase was purified from trout white muscle and some of its properties
      were investigated. The enzyme preparation was electrophoretically homogeneous;
      the molecular mass of the polypeptides was equal to 71600 +/- 550 Da, the
      specific activity was 200-500 U./mg of protein. Activation of the enzyme caused
      by acidification of the medium in the physiological range of pH was the result of
      reduction of Km for the substrate. ADP and ATP activated the enzyme, while GTP
      inhibited it. The enzyme was also inhibited by IMP (this phenomenon had never
      been described before). A change in pH within the physiological range of pH (6.6
      7.3) had no influence on ATP, GTP or IMP effects on AMP-deaminase. The enzyme
      activation by ADP was sensitive to pH. The possibilities of fish muscle AMP
      deaminase regulation under conditions of intensified metabolism is discussed.

PMID- 7718669
TI  - [Interaction between glycogen phosphorylase b and creatinine kinase from rabbit
      skeletal muscle].
AB  - Phosphorylase b association with creatine kinase has been studied by frontal
      elution affinity chromatography, using CNBr-Sepharose 4B immobilized creatine
      kinase as the affinity matrix. The quantitative parameters of this interaction
      were estimated from the volumes of phosphorylase b elution at various
      concentrations of the enzyme. The dissociation constants for phosphorylase b
      complexes with immobilized creatine kinase and of the phosphorylase b complex
      with free creatine kinase were found to be equal to 0.49 and 0.191 microM,
      respectively. In the presence of AMP the interaction between the proteins became
      weaker. With a rise in AMP concentration from 0.02 to 0.15 mM the value of the
      dissociation constants increased from 1.59 up to 9.66 microM. One molecule of AMP
      was shown to bind on the phosphorylase b-immobilized creatine kinase complex.

PMID- 7718670
TI  - [Directed cleavage of the 16S rRNA molecule at a single internucleotide bond].
AB  - Cleavage of 16S ribosomal RNA (rRNA) from E. coli "hammerhead" type ribozymes as
      well as by RNAase iI in the presence of "hymeric" (2'-deoxy-F-thymidine
      containing) oligonucleotides has been studied. The conditions for the cleavage of
      a desired single internucleotide bond have been found for a large molecule with a
      very complicated secondary and three-dimensional structure.

PMID- 7718671
TI  - [Stability of a dinitrosyl iron complex with cysteine as a candidate for the role
      of blood vessel endothelial relaxation factor].
AB  - EPR evidence is presented that stability of the dinitrosyl iron complex (DNIC)
      with cysteine [(cys)2Fe(NO+)2] which determines its capability to produce NO
      depends on the redox state of the complex. The complex is maximally stable in the
      oxidized state characterized by the d6 electron configuration of iron. The
      reducing effect of dithionite, cysteine or GSH on this particular form of DNIC
      results in its transformation into unstable paramagnetic, NO-releasing forms. The
      effect of thiols is concentration-dependent. At low cysteine concentrations (1-5
      mM and 20 microM of DNIC), thiols destabilize DNIC, acting as reducing agents.
      However, higher thiol concentrations (10 mM) added to DNIC stabilize the reduced
      forms of the complex, acting as ligands. The data obtained suggest that those
      authors who studied the vasodilatory activity of DNIC on isolated blood vessels,
      dealt with a stable oxidized form of DNIC. This form may arise due to oxidation
      of the unstable paramagnetic form of DNIC (DNIC 1:20) resulting from dilution of
      its aqueous solutions.

PMID- 7718672
TI  - [Interaction of Escherichia coli cytochrome bd with hydrogen peroxide].
AB  - The absorption spectrum of the cytochrome bd complex from Escherichia coli in the
      "as isolated" state is characterized by an intense band at approximately 648 nm
      belonging to reduced heme d oxycomplex (d2+-O2). This band is often accompanied
      by a small shoulder around 680 nm. Treatment of the oxycomplex with hydrogen
      peroxide results in the loss of the 648 nm band and increased absorbance at 680
      nm. The peak at 680 nm also appears in the difference absorption spectrum after
      addition of hydrogen peroxide to the oxidized form of the enzyme and can be
      attributed to formation of a peroxy or an oxoferryl complex of heme d. The
      increase in extinction at 680 nm is accompanied by a small red shift of the Soret
      band; the corresponding difference spectrum with lambda min = 405-410 nm and
      lambda max = 430-440 nm is of a magnitude similar to the changes in the visible
      region (delta A440-410 approximately equals 10 mM-1.cm-1). This circumstance
      favours H2O2 interaction with heme d rather than b595. The lineshape of the H2O2
      induced spectral changes does not vary throughout the hydrogen peroxide
      concentration range studied (5 microM-5 mM). The H2O2 concentration dependence on
      the 680 nm peak magnitude follows a saturation curve with apparent Kd of 30-40
      microM. The product of cytochrome bd interaction with H2O2 reacts with cyanide
      approximately tenfold slower than the free oxidized enzyme. Addition of excess
      catalase to the hydrogen peroxide-treated cytochrome bd complex fully reverses
      the H2O2-induced spectral changes. However, the rate of disappearance of these
      changes (keff approximately equals 10(-3) s-1) is ca. 10-fold slower than
      expected for the dissociation rate constant, koff, for the peroxy adduct,
      assuming reversible H2O2 binding with Kd approximately equal to 30-40 microM and
      kon > 500 M-1.s-1. This may point to H2O2 interaction with cytochrome bd, being
      essentially irreversible. The initial addition of H2O2 to heme d is likely to be
      followed by cleavage of the O--O bond, giving rise to the oxoferryl state (Fe4+ =
      O) of heme d which disappears upon removal of H2O2 by catalase due to reduction
      by endogenous electron sources.

PMID- 7718673
TI  - Effects of LiCl on triiodothyronine (T3) binding to nuclei from rat cerebral
      hemispheres.
AB  - The therapeutic effects of lithium in mania and depression are thought to be
      mediated by its effects on plasma thyroid hormone (T4, T3) levels. Inasmuch as T3
      affects transcription by binding with its nuclear receptors, in this study we
      examined whether Li+ alters T3 nuclear binding. Although plasma T3 and T4 levels
      were not affected, 125I-T3 uptake was decreased, and both in vivo and in vitro
      studies showed a significant increase in nuclear T3 binding in brain and liver
      tissue. This increase was shown to reflect an increase in maximal binding
      density. On the basis of these findings, it is proposed that Li+ exerts its
      action by inducing "cellular hypothyroidism." Integrating existing information on
      thyroid hormones and affective diseases and the effects of hypothyroidism on
      neurotransmitters thought to be altered in mania and depression, this hypothesis
      is supported and contributes to understanding of the effects of LiCl and thyroid
      hormones in affective diseases.

PMID- 7718674
TI  - Behavioral and endocrine responses to clomipramine in panic disorder patients
      with or without alcoholism.
AB  - Central nervous system serotonin functions may differ between certain subgroups
      of alcoholics, patients with panic disorder, and healthy volunteers. To
      investigate these possibilities we administered the serotonin uptake inhibitor,
      clomipramine (12.5 mg, i.v.), to patients with alcohol dependence, patients with
      panic disorder with or without alcohol dependence, and healthy volunteers.
      Alcoholics did not differ from healthy volunteers in their neuroendocrine or
      behavioral responses. In contrast, patients with panic disorder exhibited marked
      dysphoric reactions and/or panic attacks following low-dose i.v. clomipramine,
      whereas their neuroendocrine responses were similar to the other two groups.
      Patients with panic disorder may have super-sensitive postsynaptic serotonin
      receptors in areas of their central nervous system, which are important for mood
      regulation.

PMID- 7718675
TI  - Lithium and pseudohallucinations: a rare side effect.

PMID- 7718676
TI  - Alterations in hippocampal mossy fiber pathway in schizophrenia and Alzheimer's
      disease.

PMID- 7718677
TI  - A subtracted probe derived from lymphocytes of twins discordant for schizophrenia
      hybridizes to selective areas of rat brain.

PMID- 7718678
TI  - Do anticonvulsants hinder clozapine treatment?

PMID- 7718679
TI  - Schizophrenia and APP gene mutations.

PMID- 7718680
TI  - Autonomous psychosis following psychotogenic substance abuse.

PMID- 7718681
TI  - Heterozygous for ALDH2 in alcohol dependence: relationship between the ALDH2
      genotype and personality disorder in alcohol-dependent patients with the Flushing
      syndrome.

PMID- 7718682
TI  - Sleep microarchitecture in depression: commentary.

PMID- 7718683
TI  - Microarchitectural findings in sleep EEG in depression: diagnostic implications.
AB  - A 10-year review of sleep electroencephalogram (EEG)-frequency analysis in
      depression reveals several consistent microarchitectural abnormalities. Decreased
      delta amplitude or incidence, particularly in the first 100 min of sleep, has
      been reported. Elevated fast-frequency EEG has been shown in both remitted and
      symptomatic depressed patients, especially in the right hemisphere. Further,
      interhemispheric coherence is reduced in both depressed groups. These
      microarchitectural features may not be present in narcolepsy, obsessive
      compulsive disorders, or schizophrenia, despite similarities in sleep-stage
      characteristics. Collectively, these findings suggest that computer analysis of
      the sleep EEG may differentiate depressed patients from normal controls and from
      other clinical populations.

PMID- 7718684
TI  - Effect of pharmacologic treatments on the sleep of depressed patients.
AB  - Antidepressant drugs produce striking effects on sleep architecture that are best
      understood in terms of their interactions with the monoamine pathways controlling
      sleep and wakefulness. Many different antidepressant drugs, including tricyclic
      antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and selective 5
      hydroxytryptamine (5-HT; serotonin) reuptake inhibitors (SSRIs), decrease rapid
      eye movement (REM) sleep. The reduction in REM sleep produced by antidepressants
      may be an important part of their mechanism of action; however, the ability of
      new antidepressant compounds, such as nefazodone and moclobemide, to increase REM
      sleep throws doubt on this suggestion. The effects of antidepressants on slow
      wave sleep (SWS) are quite diverse; in general, antidepressants having
      significant 5-HT2A/2C receptor antagonist properties increase SWS, whereas other
      drugs, such as SSRIs or MAOIs, either lower SWS or produce no change. Sleep
      continuity is improved acutely following administration of antidepressants with
      sedating properties such as certain TCAs, trazodone, and mianserin. Some
      nonsedating drugs (ritanserin and nefazodone) also improve sleep continuity
      measures, possibly through 5-HT2A/2C receptor blockade.

PMID- 7718685
TI  - Sleep, its subjective perception, and daytime performance in insomniacs with a
      pattern of alpha sleep.
AB  - Intrusion of alpha activity, an electroencephalographic (EEG) pattern typical for
      wakefulness, into sleep stages has repeatedly been described and investigated in
      various populations. Some studies suggested that it is a less deep and
      restorative sleep, but others did not support this interpretation. The present
      study was carried out to collect ample data on neurophysiology and subjective
      experience of sleep and on daytime cognitive performance to clarify this point. A
      sample of 128 primary insomniacs was investigated with polysomnography (PSG) that
      was submitted to a computerized, automatic analysis of alpha activity during
      sleep. It yielded two groups of 64 Ss each with a normal, that is, nonalpha sleep
      EEG and with alpha-sleep, respectively. Contrasting the two groups for PSG showed
      that alpha sleep Ss had significantly more stage 4 and a (nonsignificant)
      tendency for more awakenings. Subjectively, they largely underestimated
      intermittent wake time and consequently overestimated sleep duration by 50 min.
      The performance test battery showed a difference in one test only, that is, a
      better short-term memory function by alpha sleep Ss. In conclusion, there was no
      result supporting the assumption that alpha sleep is less restorative, but a
      significant lack of perception of intermittent awakenings during night sleep by
      alpha sleep Ss was found. The authors propose an explanation and point to the
      implications this misperception might have for the clinician.

PMID- 7718686
TI  - Factors influencing the failure of dental glass ionomer luting cement due to
      contraction.
AB  - Glass ionomer cement used to fix a post within the root of a tooth undergoes
      cohesive failure on setting. This study aimed to determine the importance of
      humidity, substrate material and post design on cement failure. Nine groups of
      five specimens were prepared: groups 1-3 addressed the influence of post design
      and sectioning process on cement failure, while groups 4-9 examined the
      interaction between the cement, substrates and humidity. Replicas were prepared
      of all specimens and viewed using scanning electron microscopy. It was concluded
      that humidity and substrate influenced the failure of glass ionomer cement
      whereas post design did not.

PMID- 7718687
TI  - Derivatization of a new poly(ether urethane amide) containing chemically active
      sites.
AB  - A novel poly(ether urethane amide) was synthesized by chain-extending the
      prepolymer with fumaric acid, resulting in a polymer exhibiting superior
      mechanical properties and containing chemically active derivatization sites,
      stemming from the fumaramide double bond. The derivatization of the active sites
      was performed via a Michael-like addition of amine-terminated poly(ethylene
      oxide) chains, which when performed in bulk, greatly affected the mechanical
      properties of the polymer, except in the case in which a relatively high
      molecular weight was grafted. Surface grafting of the polymer led to a
      significantly lower effect on its mechanical properties, which was minimal when a
      high molecular weight molecule was used.

PMID- 7718688
TI  - Late degradation tissue response to poly(L-lactide) bone plates and screws.
AB  - Patients with fractures of the zygomatic bone were treated with high molecular
      weight poly(L-lactic) acid (PLLA) bone plates and screws. Three years after
      implantation four patients returned to our department with a swelling at the site
      of implantation. At the recall of the remaining patients we found an identical
      type of swelling after the same implantation period. To investigate the nature of
      the tissue reaction, eight patients were reoperated for the removal of the
      swelling. The implantation period of the PLLA material varied from 3.3 to 5.7
      years. Microscopic evaluation and molecular weight measurements were performed.
      The excised material showed remnants of degraded PLLA material surrounded by a
      dense fibrous capsule. Ultrastructural investigation showed crystal-like PLLA
      material internalized by various cells. The results of this investigation suggest
      that the PLLA material slowly degrades into particles with a high crystallinity.
      The intra- and extracellular degradation rate of these particles is very low.
      After 5.7 years of implantation, these particles were still not fully resorbed.

PMID- 7718689
TI  - Characterization of lacrymal component accumulation on worn soft contact lens
      surfaces by atomic force microscopy.
AB  - The purpose of this study was to investigate lacrymal component accumulation on a
      soft contact lens (SCL) surface after various periods of continuous wear, using
      the recently developed atomic force microscopy (AFM). AFM allowed high resolution
      images of unworn and worn SCL, and presented two main advantages. 1. The SCL are
      analysed under nearly physiological conditions without being dried or destroyed.
      So the same SCL was analysed at various times during a long wearing period. To
      identify the deposited tear proteins, a qualitative analysis of solubilized
      deposit by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE)
      on 4-15% gradient minigels was performed as well. We present typical images which
      emphasize the importance of the coating by lacrymal components. AFM analysis of
      worn SCL showed the deposition on the surface of a uniform lacrymal component
      coating (named deposit type I) with a progressive accumulation of numerous
      discrete granules (named deposit type II). SDS-PAGE of extracted deposits
      revealed the main tear proteins as: IgA, lactoferrin, tear lipocalin and lysozyme
      and the unknown protein of molecular weight 30,000. There is no clear difference
      in the protein patterns of the two types of deposits. Furthermore, a particular
      mode of use of AFM is described to illustrate the potential of this technique as
      a local tool for measuring protein coating thickness. Thus, for analysis of
      protein deposits on SCL surfaces, SDS-PAGE on minigels and AFM were easy and
      rapid to perform. When associated, these two techniques could find use in a wide
      range of worn SCL evaluation and most generally in biocompatibility evaluation
      studies.

PMID- 7718690
TI  - Long-term histological evaluation of hydroxyapatite ceramics in humans.
AB  - We have investigated the interface between bone and hydroxyapatite (HA)
      chronically implanted in man. By light microscopy, HA appeared to bind directly
      to bone without intervening fibrous tissue. By transmission electron microscopy,
      two patterns were noted: (1) HA either bound directly to bone; or (2) electron
      dense material intervened between HA and bone. The orientation of bone collagen
      fibres likewise showed two patterns: (1) collagen fibres were oriented parallel
      to the HA; or (2) the fibres were aligned perpendicularly. We have observed
      similar binding properties of HA to the jaw bone of humans in vivo and in vitro.

PMID- 7718691
TI  - Intrinsic factors of apatite influencing its amorphization during plasma-spray
      coating.
AB  - Hydroxyapatite coatings were prepared from differently treated starting powders
      to investigate the intrinsic factors of apatite influencing its amorphization
      during plasma-spray coating. The joint analyses of X-ray diffraction and infrared
      spectra show that the vacancies located on missing hydroxyl sites retard the
      amorphous/crystalline conversion and enforce retention of the amorphous
      component; the absorbed water molecules that pre-exist in the starting powder can
      be incorporated into the vacancies in the hydroxyapatite lattice during plasma
      spray coating and compensate for the missing hydroxyls so as to promote the
      transformation of amorphous into crystalline apatite in the coating process. The
      more vacancies there are in the apatite structure due to missing hydroxyl sites,
      the more amorphous the component in the resultant coatings. Moreover, the
      amorphous phase formed in this way is stable in room conditions.

PMID- 7718692
TI  - Space-cutting model of hydroxyapatite.
AB  - The possibility of substitution of trace elements such as Mg2+, Sr2+ and Ba2+
      into the columnar Ca2+ positions of hydroxyapatite was examined by computer
      graphics with a personal computer and a space-cutting method. Data on the
      structural coordinates of the hydroxyapatite were put into a protein graphics
      program in Angstrom units. The connection of each element, with front and rear,
      was displayed by the shade-line erasing method, and the solidity of the image was
      expressed by the degree of lightness from the light source. The space-cutting
      model was obtained by selecting the cutting plane with three atoms in the
      crystal. Rotating the graphics freely around the X, Y and Z axes gives a view
      from any direction. The computer graphics suggested visually how the lattice
      dimensions expand with Sr2+ and Ba2+ substitution and contract with Mg2+
      substitution.

PMID- 7718693
TI  - Neutrophil-mediated degradation of segmented polyurethanes.
AB  - The biostability of polyurethanes was evaluated using a human neutrophil cell
      culture. The polymers were synthesized with 14C radiolabelled components
      incorporated into the polyurethane chain and the amount of radiolabel released
      during exposure to cells and medium was used as a marker for material
      degradation. The effect of diisocyanate, soft segment and chain extender
      chemistry on the susceptibility of polymer degradation was examined. All polymers
      showed a release of material into the tissue culture medium which was unrelated
      to the cells. A significant cell-dependent release of radiolabel-containing
      material was found from one of the polymers (a polyester urea-urethane,
      TDI/PCL/ED) which increased linearly up to 96 h. The polyether-containing
      polyurethanes showed no significant cell-mediated degradation under similar
      conditions as measured by radiolabel release. Scanning electron microscopy (SEM)
      showed that the cells adhered to the different polyurethanes. However, no effect
      of neutrophils on polymer structure could be detected by this technique. The
      cellular response to each polymer was evaluated by measuring release of elastase
      like activity (ELA) into the tissue culture media. After 24h TDI/PCL/ED showed
      the highest levels of ELA in the tissue culture medium. When TDI/PCL/ED was
      incubated with commercial elastase in vitro, a significant release of radiolabel
      was found which was comparable to the amount of radiolabelled material released
      from this polymer in contact with the neutrophils in culture. No significant
      amount of radiolabel was released from the corresponding polyether material
      (TDI/PTMO/ED) under similar conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718694
TI  - Characterization of human neutrophils adherent to organic polymers.
AB  - The adherence of human neutrophils to surfaces from organic polymers (Pellethane,
      two types of polyvinyl chloride (PVC), polypropylene and polyethylene) is
      associated to a different extent with O2- formation. No comparable differences
      were observed for the liberation of the granular enzyme elastase. Only cells
      attached to Pellethane responded strongly after a second stimulation by opsonized
      zymosan, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and aggregated IgG. The
      expression of related antigens on adherent cells was measured by a cell-ELISA
      (enzyme-linked immunosorbent assay). Cells adherent to five various untreated
      organic polymers show no differences of their Fc gamma- and C3bi-receptors. A
      considerable increase of all investigated cellular antigens was observed for
      neutrophils adherent to films precoated with autologous plasma. The adherence
      rates and the viability for cells adherent to different materials were similar
      and may not account for the observed differences in O2- production during the
      primary adherence reaction and a further secondary stimulation.

PMID- 7718695
TI  - Reactivity and the fate of some composite bioimplants based on collagen in
      connective tissue.
AB  - Three composite materials based on collagen gel prepared with ISC40 and
      supplemented with the tripeptide glycine-histidine-lysine (GHK) mixed with
      bioglass (BAS O), pure hydroxyapatite (grain: 0.5-1.0 microns and 13-23 microns)
      and shredded beef bone were tested in the laboratory rat and guinea-pig. In the
      course of 49 d, no signs of infectious inflammation or incompatibility were
      observed around subcutaneously installed bioimplants. Particles of glass and
      hydroxyapatite became subject to phagocytosis. Bone fragments were completely
      resorbed, and no signs of osteogenic activity were detected in the neighbourhood.

PMID- 7718696
TI  - Fracture toughness and flexural strength of dental ceramics for titanium.
AB  - Three brands of dental ceramics for veneering to titanium: TitanBond (O'Hara), Ti
      Ceram (Ducera) and Titankeramik (Vita) were tested to compare their fracture
      properties in wet and in dry conditions. Eight polished and precracked specimens
      of each material were stored in water at 37 degrees C for 28 d and then preloaded
      in a four-point bending jig with a constant load of 50 N for 24 h under water.
      Five of the specimens were fractured by a four-point bending test also under
      water at 37 degrees C. Crack depths were measured in three different positions in
      each of the remaining three specimens. Fracture load and crack depths were used
      to calculate the fracture toughness. Another ten polished specimens were used to
      measure the flexural strength with a four-point bending test after storage in
      water at 37 degrees C for 28 d. Equal procedures and numbers of specimens were
      used to measure fracture toughness and flexural strength without preloading and
      storage in water.

PMID- 7718697
TI  - Sexual selection, honest advertisement and the handicap principle: reviewing the
      evidence.

PMID- 7718698
TI  - Variability of neoplastic parameters in colon tumours, and its significance in
      diagnostic practice.
AB  - We have reviewed the value of individual variability in the reaction of tissues
      to treatment with carcinogens, and the manifestation of this variability in
      different morphological (histological, morphometric, and ultrastructural),
      histochemical and immunohistochemical parameters generated in tumorous tissues.
      Moreover, we also reviewed data in the literature on individual variability in
      the manifestation of some biochemical and immunochemical markers which are
      accumulated in the serum of tumour-bearing patients and which are characteristic
      for the different phases of tumourigenesis. The high variability of different
      tumorous parameters suggests that none can be utilized alone as a conclusive
      marker of neoplasia and that only their combined use can give objective
      information. We also reviewed the impact of this variability in the evaluation of
      various pathological methods to detect different stages of neoplastic
      transformation in the colon. It has been concluded that none of the present
      approaches can be absolutely conclusive and without false results, and that
      objective information regarding early cancerous changes may be obtained only by
      use of combined analyses utilizing several laboratory methods. The diagnostic
      procedures should be based on the complex utilization of all appropriate methods
      using the quantitative interpretation of the obtained data. Multivariate analysis
      of many parameters should be very effective for the prediction of therapeutic
      results.

PMID- 7718699
TI  - [Early postnatal child development and its significance for inpatient care].

PMID- 7718700
TI  - [What is the connection between holistic thought in nursing and science].

PMID- 7718701
TI  - [Integration of nursing science into practice].

PMID- 7718702
TI  - [Anna Gogl, a new co-editor introduces herself].

PMID- 7718703
TI  - [Supervision for nursing personnel: more than mental health? The importance of
      supervision for the professionalization of nursing].

PMID- 7718704
TI  - [The struggle for differences--the field of medicine and the changing nursing
      profession].

PMID- 7718705
TI  - [Professional nursing practice--selected results of a study based on an action
      oriented understanding of professionalization].

PMID- 7718706
TI  - [Feeding of severely demented patients in institutions: interviews with
      caregivers in Israel].

PMID- 7718707
TI  - [It is important to me, not just to be fixed on the diseases. Nurses talk about
      their profession].

PMID- 7718708
TI  - [Chains of action--chains of power: new challenges for nursing management. 1].

PMID- 7718709
TI  - [Bronchoalveolar lavage: limiting factors in its standardization].

PMID- 7718710
TI  - [Multicenter comparative study of synthetic salmon calcitonin administered
      nasally in the treatment of established postmenopausal osteoporosis].
AB  - We study the effectivity and tolerance of synthetic salmon calcitonin nasally
      administered (Miacalcic) in the treatment of established postmenopausic
      osteoporosis. During one year, two randomized groups of postmenopausic women
      diagnosed of osteoporosis were treated in an outpatient service either with 1 gr
      of calcium element per day during the whole study or with 100 daily I.U. of
      salmon synthetic calcitonin nasally administered in patterns of 14 days and the
      same period of rest, plus a supplement of 500 mgr of calcium element per day.
      Globally, 43 patients were assessed at the end of the study in the calcitonin
      plus calcium group and 45 in the group receiving only calcium. The main
      evaluation parameters were pain and presence of new fractures. At the beginning
      and at the end of the study, complementary tests of blood biochemistry were
      conducted, including alkalin phosphatase, calcium, phosphorus and uric acid, as
      well as calcium, hydroxiprolin and creatinini in the urine. The results showed a
      significant improvement of pain (p < 0.001) in the group treated with calcitonin,
      supported by a lower consumption of analgesics. The rate of vertebral fractures
      determined according to the Meunier's index, was also significantly lower (p <
      0.001) in the group treated with calcitonin at the end of the study period. These
      results suggest that, compared to only calcium, nasally administered calcitonin
      precludes the formation of new vertebral fractures during one year of treatment
      and it is effective in terms of pain reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718711
TI  - [Miliary tuberculosis. Autopsy study of 29 cases].
AB  - A retrospective anatomoclinic study of 29 cases of miliary tuberculosis, selected
      from 2.808 necropsies carried out at Hospital Central de Asturias between 1971
      and 1994, is described. Fifty eight per cent of the patients were older than 50
      years. Predisposing factors were identified in 80%: diabetes, alcoholism, chronic
      hepatopaty, silicosis, chronic renal failure, immunessupresive treatment and
      malignant neoplasms. A premorten correct clinical diagnosis were done in 8 cases
      (27.5%) and were suspected in 4 (13.7%). Typical miliary radiologic pattern was
      established in 17%. The more frequently affected organs were lungs (100%), liver
      (82%), spleen (75%), lymphatic nodes (55%) and bone marrow (41%). Early diagnosis
      and treatment is nowadays more difficult because of increasing of cryptic
      tuberculosis, involvement of resistant organs (pancreas), new predisposing
      factors (chronic renal failure), new risk groups (AIDS) and lack of demonstrative
      clinical and radiologic findings, so is necessary to maintain suspect of this
      disease always in mind.

PMID- 7718712
TI  - [With respect to Tinel and Phalen's signs].
AB  - The increment sensibility of the median nerve's compressed fibres in the carpal
      tunnel constitute the basis of the most known clinical tests, Phalen's test an
      Tinel's sign, used for diagnosis of the Carpal Tunnel syndrome. The frequence of
      these signs found in the literature is very variable, by this reason we realized
      this work, for determining the correlation between these tests and the clinical
      features and the electro-diagnosis. In our series (288 hands) the Tinel's sign
      demonstrate significative correlation with the motor and sensory conduction
      velocity (p < 0.05), showing significative increase of its frequence when distal
      motor and sensory latency were upper 4.5 ms. Phalen's test non correlated with
      any electrical parameters. Nevertheless, 97% of cases with positive Phalen's test
      were typical clinic forms of Carpal Tunnel syndrome, white 85% of cases with
      positive Tinel's sign concerned to typical group.

PMID- 7718713
TI  - [Severe gastrointestinal complication of Behcet's disease].
AB  - We describe a case of Behcet's syndrome with ileoceal affection of the
      gastrointestinal track, torpid course evolving to an intermittent febrile
      syndrome and associated to clinical signs of acute abdomen and latter septic
      complication due to a fecaloid fistula after surgery. We discuss the similarities
      with the inflammatory intestinal disease and the problem of the diagnosis and
      treatment of this particular implication of Behcet's syndrome.

PMID- 7718714
TI  - [Resolution with steroid therapy of an idiopathic esophageal fistula in a patient
      with AIDS].
AB  - We present a case of AIDS with idiopathic esophagic fistula which had a positive
      response to steroid therapy. We discuss the diagnostic potential and the
      therapeutic attitude in these cases.

PMID- 7718715
TI  - [Cytologic and biochemical component in 203 bronchoalveolar lavages. Reference
      values].
AB  - The bronchoalveolar lavage (BAL) is considered a basic technique as a diagnostic
      aid in Pneumology. However, one of the main problems faced by the clinician is
      the lack of standardization of the technique. This has been resolved through the
      drafting of international standards. The other problem is the lack of what might
      be called a "reference" BAL. In order to establish a reference BAL, we analyzed
      203 BAL divided in two groups: a control group and a pathologic group, make up by
      extrinsic asthma, intrinsic asthma, pulmonary infections, diffuse interstitial
      pneumopathies, bronchopulmonary tumors and chronic bronchitis. We have studied
      both the cytologic and the biochemical component of the BAL. Among the
      biochemical markers, we have considered; carcinoembrionary antigen (CEA),
      tissular polypeptidic antigen (TPA), neuronal specific enolase (NSE), ferritin
      (FER), calcitonin (CT), ACTH, histamin (HIS) and prostaglandin (PGE2). In order
      to establish the reference values, we have used the modified Baye's theorema. The
      BAL that we obtained was the following: volume 20 ml, cells 35 x 10(5) cells/ml,
      macrophages 77%, lymphocytes 22%, neutrophils 4%, eosinophils 2%, CEA 14 ng/mg,
      TPA 84 U/g PT, NSE 5 ng/mg PT, FER 42 ng/mg PT, CT 15 pg/mg PT, ACTH 51 pg/mg PT,
      HIS 1.22 ng/mg PT, PGE2 35 pg/mg PT.

PMID- 7718716
TI  - [Lupus vulgaris. Treatment with 3 drugs].
AB  - We report two cases of lupus vulgaris one of them on scar of scrofuloderma. We
      review the treatment of the skin tuberculosis (TBC) and we observed the favorable
      development to the total regression, using rifampin-isoniazid-pyrizinamide in the
      first two months and rifampin-isoniazid the four months left to complete six
      months of global therapy. We discard the monotherapy as treatment for this
      disease.

PMID- 7718717
TI  - [Acute rhabdomyolysis and tetraparesis secondary to hypokalemia due to ingested
      licorice].
AB  - The glycirrinic acid, a common component of the natural licorice, has a potent
      mineralacorticoid effect (primary pseudohyperaldosteronism) which may cause
      severe hypokalemia and acute rhabdomyolysis. We present the case of a 36-years
      old patient who, as the result of the intake of five daily licorice sticks (25
      gr/day) for one month, developed analytical and clinical signs of acute
      rhabdomyolysis associated to the typical disorders of mineralcorticoid excess,
      that is, severe hypokalemia, arterial hypertension and metabolic alkalosis. The
      relevance of this clinical case lies on the low frequency of this finding and on
      the need that physicians working at emergency care centers must be aware of the
      onset of acute tetraparesis related to hypokalemia secondary to licorice ingesta.
      The early detection of this pathology is essential, since it will result in the
      beginning of an specific treatment, avoiding thus, as far as possible, the severe
      complications that might appear.

PMID- 7718718
TI  - [Mesenteric panniculitis: a case of acute and fatal presentation].
AB  - Mesenteric panniculitis is a rare process in which there is an inflammation of
      the mesenteric adipose tissue due to unknown causes and mechanisms. It evolves
      with abdominal pain and/or mass, among other symptoms, generally with a chronic
      and bening course. The concomitant tests are generally non-specific, the
      diagnosis being anatompathological. We present the case of an old woman who died
      hours after starting an episode of abdominal pain. The autopsy showed the
      presence of mesenteric panniculitis. The sudden onset of the clinical signs,
      without other justifying cause than the panniculitis itself, suggests that this
      must be considered in the differential diagnosis of acute abdominal pain. In
      addition, the absence of other morphological findings which could suggest a fatal
      cause make us to consider the relationship between this and the panniculitis.

PMID- 7718719
TI  - [Denomination and general concept of dementia].
AB  - We believe that dementia will be, at the beginning of the next century, the
      fourth cause of mortality. It is a frequent error to consider dementia just as
      problem related to aging. The definition and diagnosis of the entity is clinical
      and not anatomopathological, requiring a detailed analysis of the cognoscitive
      functions, the relationship with the occupational, social and familiar
      environment of the patient and the search of potential etiological factors. In
      this paper, we commnet the general concept of dementia in order to clarify the
      implication of the term dementia and to reduce the frequent inaccuracy in its use
      and diagnosis.

PMID- 7718720
TI  - [Pulmonary adenocarcinoma associated with bullous disease].

PMID- 7718721
TI  - [Interferon-alpha and hyperthyroidism].

PMID- 7718722
TI  - [Subphrenic abscess related to hidden perforated duodenal ulcer].

PMID- 7718723
TI  - [Malignant fibrous histiocytoma or pseudotumor of fusiform cell?].

PMID- 7718724
TI  - [Malignant fibrous histiocytoma or pseudotumor of fusiform cell?].

PMID- 7718725
TI  - [Cutaneous myiasis due to Dermatobia Hominis].

PMID- 7718726
TI  - [Malignant fibrous histiocytoma of bone].

PMID- 7718727
TI  - [Endocarditis by Eikenella corrodens in intravenous drug addicts].

PMID- 7718728
TI  - [Facial paralysis as first manifestation of tetanus].

PMID- 7718729
TI  - [Lectures at the annual meeting of the German Association for Biomedical
      Technology. Rostock, 22-24 September 1994].

PMID- 7718730
TI  - Subsite-specific risk factors for colorectal cancer: a hospital-based case
      control study in Japan.
AB  - To investigate the subsite-specific risk factors for colorectal cancer, we
      conducted a case-control study, using a common questionnaire which inquired about
      general lifestyles over the past five years (1988-92), at the Aichi Cancer Center
      Hospital, Nagoya, Japan. This study compared 432 patients with
      histopathologically diagnosed colorectal cancer (94 proximal colon [cecum,
      ascending colon, transverse colon]; 137 distal colon [descending colon, sigmoid
      colon]; 201 rectum [rectosigmoid, rectum]); and 31,782 first-visit outpatient
      controls who were free from cancer. In both genders, habitual smoking selectively
      increased the risk for rectum cancer. Soft or loose feces increased the risk for
      all subsites of colorectal cancer, particularly in female rectum cancer (odds
      ratio [OR] = 4.5). Among female dietary habits, Japanese-style foods decreased
      the risk for distal colon cancer, but increased the risk for proximal colon
      cancer. These results suggested that the risk factors for colorectal cancer
      differ by subsite among such a low-risk population as the Japanese. It is
      suggested also that 'irritable bowel' (soft or loose feces) might be associated
      with distal subsites of colorectal cancer, independently or combined with
      habitual smoking.

PMID- 7718731
TI  - Parental ages at birth in relation to a daughter's risk of breast cancer among
      female participants in the Framingham Study (United States).
AB  - Data from the Framingham Heart Study, collected in Framingham, MA (United States)
      during 1948-86, were used to evaluate the relation of parental age at birth to
      the risk of breast cancer among daughters. After 38 years of follow-up, 149
      breast cancer cases occurred among 2,662 women. All but two cases were confirmed
      by histologic report. The rate of breast cancer increased among daughters with
      increasing maternal age at birth up to the mid-30s, where the rate levelled off.
      A similar pattern was observed with paternal age. After adjustment for other
      confounding factors and paternal age, the rate ratios for breast cancer in
      daughters whose mothers were aged 26 to 31 years and 32 or more years at their
      birth, relative to women whose mothers were aged 25 years or younger, were 1.5
      (95 percent confidence interval [CI] = 1.0-2.4) and 1.3 (CI = 0.8-2.2),
      respectively. However, there was no longer an association between paternal age at
      birth and risk of breast cancer after controlling for maternal age and other risk
      factors.

PMID- 7718732
TI  - The relation of body size to plasma levels of estrogens and androgens in
      premenopausal women (Maryland, United States).
AB  - We analyzed data from a cross-sectional study of 107 premenopausal women to
      evaluate the relations of height, weight, and body mass index (BMI) with plasma
      hormone levels. Participants were 20- to 40-year old women residing in Maryland
      (United States), whose reported menstrual cycle lengths were not more than 35
      days and whose measured weights for height were 85 to 130 percent of 'desirable'
      based on 1983 Metropolitan Life Insurance tables. Fasting blood specimens were
      collected on each of days 5-7, 12-15, and 21-23 of every participant's menstrual
      cycle and pooled to create follicular, midcycle, and luteal phase samples,
      respectively, for analysis. Adjusted for age, taller women had significantly
      higher follicular-phase plasma-estradiol levels (percent difference/cm = 1.5, 95
      percent confidence interval [CI] = 0.3-2.7, and heavier women had significantly
      lower plasma sex-hormone binding globulin (SHBG) levels averaged across the
      menstrual cycle phases (percent difference/kg = -1.2; CI = -1.9-(-0.6). Body
      weight within the range studied, however, was not related significantly to the
      concentration of SHBG-bound estradiol during any phase of the menstrual cycle.
      The results of this cross-sectional study suggest a possible mechanism by which
      height may influence breast cancer risk.

PMID- 7718733
TI  - The association of body size and large bowel cancer risk in Wisconsin (United
      States) women.
AB  - Body size is associated with the risk of many diseases, including diabetes, heart
      disease, and some cancers. To evaluate the association of body size with large
      bowel cancer, height and weight measurements were ascertained by telephone
      interview from 779 Wisconsin (United States) women with newly reported diagnoses
      of carcinoma of the colon and rectum. Controls (n = 2,315) interviewed for this
      case-control study were selected randomly from Wisconsin driver's license files
      and Health Care Financing Administration files. The effects of weight and height
      were examined using multiple logistic regression to control for potential
      confounding variables. In this study, weight adjusted for height increased the
      risk of colon cancer (odds ratio [OR] for 72.57-148.33 kg cf 36.29-58.05 kg =
      1.4, 95 percent confidence interval [CI] = 1.0-1.9) but did not increase the risk
      of rectal cancer. Height did not influence risk for cancer of either the colon or
      the rectum. Left-colon subsite analysis showed especially strong associations
      with current weight and with percent change in weight since age 18. These data
      suggest that a dose-response relationship exists between body size and risk of
      colon cancer in women; body size did not appear to influence risk of rectal
      cancer.

PMID- 7718734
TI  - Parity and risk of thyroid cancer: a nested case-control study of a nationwide
      Swedish cohort.
AB  - The association between parity and risk of thyroid cancer was examined in a case
      control study nested within a cohort of Swedish women born 1925-60. A total of
      1,409 cases of thyroid cancer were compared with 7,019 age-matched controls. Odds
      ratios (OR) and 95 percent confidence intervals (CI) were calculated as estimates
      of relative risk. A weak association was found between parity and risk of thyroid
      cancer (OR for ever-parous women cf nulliparous was 1.1, CI = 1.0-1.3). For the
      subset of papillary cancers, there was a significantly increased risk (OR for
      ever-parous cf nulliparous = 1.3, CI = 1.0-1.6), and among women diagnosed at the
      age of 50 or older, there was a positive linear trend with increasing number of
      livebirths. Women during the first year after a livebirth had an increased risk
      of thyroid cancer compared with women who delivered 10 or more years before; this
      association was most prominent among uniparous women (OR = 2.5, CI = 1.1-5.9). An
      increased risk was also apparent for age over 20 years at livebirth (among
      uniparous women) and age over 25 years at last livebirth (among multiparous
      women). A negligible effect of parity on thyroid cancer risk was seen, but each
      livebirth may have a short-term and age-dependent promoting effect.

PMID- 7718736
TI  - Case-control study of squamous cell cancer of the oral cavity in Denmark.
AB  - A population-based case-control study was designed to examine if the risk of
      developing intra-oral squamous-cell carcinoma in Denmark was associated with
      occupation, marital status, residence, dental status, and exposure to coffee,
      tea, tobacco, and alcohol. Cases consisted of 161 consecutively-admitted incident
      patients with histologically verified, primary, intra-oral squamous-cell
      carcinoma treated at the Aarhus University Hospital from January 1986 to November
      1990. For each case, three controls of the same gender and age were selected
      randomly from among nonhospitalized residents in the hospital's catchment area
      (some 1.4 m inhabitants). Four hundred of the selected 483 controls participated
      in the study. Risk was associated significantly with marital status, residence,
      dental status, alcohol consumption, and exposure to tobacco. When correcting for
      tobacco and alcohol consumption, only marital status and dental status remained
      significant. The association between risk and marital status was particularly
      prominent among divorced compared with married persons (odds ratio [OR] = 2.3, 95
      percent confidence interval [CI] = 1.1-4.6). Persons with less than five teeth
      had an OR of 2.4 (CI 1.3-4.1) compared with persons with 15 or more teeth.
      Tobacco and alcohol exposure were the strongest individual risk-indicators in
      both lifetime and current consumption estimates, and their composite effect was
      particularly strong. Compared with nonusers, OR for tobacco (> 20 g/d) adjusted
      for alcohol = 5.8 (CI = 3.1-10.9); OR for alcohol (> 5 drinks/d) adjusted for
      tobacco = 8.4 (CI = 4.0-17.6). The OR for heavy users of tobacco and alcohol (>
      20 g tobacco/d and > 5 drinks/d) was 80.7 (CI = 21.8-298.8). These results
      confirm that tobacco and alcohol contribute significantly to the risk of
      developing oral cancer. There were no significant differences between the risk
      estimates for the two genders or young and old persons. Two simulation studies
      indicate that the observed risk associated with tobacco and alcohol consumption
      cannot be explained reasonably by a high consumption among the 83 nonrespondents.

PMID- 7718735
TI  - Diet, alcohol, and smoking and the occurrence of hyperplastic polyps of the colon
      and rectum (United States).
AB  - Hyperplastic polyps of the colon reveal a geographic distribution similar to that
      of colorectal cancer and adenomatous polyps. However, unlike adenomas--known
      precursors of colorectal cancer--little is known about the etiology or clinical
      significance of the hyperplastic polyp. In this prospective study, we set out to
      determine the main dietary and other lifestyle factors in the United States that
      might be associated with this lesion. Hyperplastic polyps of the distal colon and
      rectum were diagnosed in 219 of 12,922 men of the Health Professionals Follow-up
      Study having had an endoscopic procedure between 1986 and 1992, and 175 of 15,339
      women of the Nurses' Health Study who had undergone an endoscopy for a variety of
      reasons between 1980 and 1990. After adjusting for age, family history of colon
      cancer, history of previous endoscopy, and total energy intake using multiple
      logistic regression, those consuming 30 g or more of alcohol per day were at
      increased risk relative to nondrinkers among men (relative risk [RR] = 1.69; 95
      percent confidence interval [CI] = 1.01-2.80) and women (RR = 1.79, CI = 1.02
      3.15). Current smoking also was found to be associated strongly positively with
      hyperplastic polyps in men (RR = 2.45, CI = 1.59-3.75) and women (RR = 1.96, CI =
      1.16-2.86). High intake of folate was associated inversely with risk in both men
      (RR = 0.74, CI = 0.49-1.11, between high and low intakes of folate) and women (RR
      = 0.45, CI = 0.28-0.74, between high and low intakes of folate). Among
      macronutrients, a suggestive increase in risk existed with intake of animal fat,
      although this was attenuated in the full multivariate model (RR[men] = 1.48, CI =
      0.94-2.41, and RR[women] = 1.22, CI = 0.77-1.94) between high and low quantities
      of animal fat intake. These prospective data provide evidence of associations
      between low folate intake, alcohol consumption, and current cigarette smoking,
      and risk of hyperplastic polyps of the distal colon and rectum. These same
      factors also have been found to be related to adenoma and cancer of the colon.
      The hyperplastic polyp is an indicator of populations at high risk for colorectal
      carcinoma, and it also may serve as a marker for factors that influence
      neoplastic evolution.

PMID- 7718737
TI  - Cancer mortality in Italian migrants and their offspring in Canada.
AB  - Studies on the offspring of migrants provide important information on the
      contribution of environmental and genetic factors in the etiology of various
      cancers. The aim of the present study is to analyze the cancer risk in Italian
      migrants (Canadian residents born in Italy) and their offspring compared with the
      host population. Odds ratios (OR) and 95 percent confidence intervals (CI) by
      site and birthplace categories (migrants, pure and mixed Italian-parentage
      Canadians) were calculated by means of a case-control study using the 'other
      cancer deaths' as controls and taking the host population as the reference
      category. The study shows that Italian migrants retain a significantly low risk
      for a series of cancers: colon (OR = 0.9 in males and 0.7 in females); lung (OR =
      0.8 in males and 0.5 in females); and breast (OR = 0.9). For all of these sites,
      risks in the offspring of Italian migrants were not different from those of the
      host population, with some differences between the genders with respect to cancer
      of the colon. Stomach cancer presents a significantly high rate in migrants (OR =
      1.9 in males and 2.4 in females), consistent with the population of Italy; in
      their offspring, risks are similar to those in the host population. The risk of
      cancer in the offspring of migrants is, for many sites, intermediate between the
      host population and the Canadian residents born in Italy. This finding possibly
      is related to the larger integration of the offspring than their parents in the
      cultural and social environment of the host population.

PMID- 7718739
TI  - Power lines, viruses, and childhood leukemia.

PMID- 7718738
TI  - Abortion and breast cancer risk in seven countries.
AB  - Epidemiologic studies have been inconsistent in suggesting an association between
      abortion and breast cancer risk. Whether the protection provided by a full-term
      pregnancy also results from a short-term pregnancy or whether a prematurely
      terminated pregnancy could increase the risk of breast cancer is unclear. Data
      from a large, international collaborative study were used to evaluate the
      association between abortions, whether spontaneous or induced, and breast cancer
      risk. The data from seven countries included 3,958 breast cancer cases and 11,538
      hospital controls with information on abortion history obtained through
      interviews. Compared with nulliparous women with no abortion (baseline), the odds
      ratios (OR) and 95 percent confidence intervals (CI) were: for nulliparous women
      with a history of prior abortion, 0.86 (CI = 0.68-1.08); for parous women with no
      history of abortion, 0.63 (CI = 0.57-0.69); for parous women with abortion before
      first birth, 0.82 (CI = 0.69-0.97); and, for parous women with abortion only
      after first birth, 0.70 (CI = 0.63-0.79). When restricting analysis to parous
      women, those with a history of abortion exhibited an elevated OR suggesting a 29
      percent risk increase if the incomplete pregnancy occurred before first birth (CI
      = 1.16-1.36) and an 11 percent risk increase for abortion only after first birth
      (CI = 1.02-1.20) compared with women without such history. The associations
      observed were stronger among the youngest women. These results do not support a
      large overall association between abortion and breast cancer risk.

PMID- 7718740
TI  - Cancer risk following polymyositis and dermatomyositis: a nationwide cohort study
      in Denmark.
AB  - Polymyositis and dermatomyositis (PM/DM) have been associated with cancer,
      although the long-term risks are poorly understood. To evaluate the risk of
      cancer by time periods subsequent to PM/DM diagnosis, a cohort of 539 patients
      hospitalized with PM/DM in Denmark between 1977 and 1989 was identified from the
      Danish Central Hospital Discharge Register. Cancer incidence among cohort members
      was ascertained by linkage to the Danish Cancer Registry using a unique personal
      identification number. The overall cancer risk was elevated significantly among
      patients with DM (standardized incidence ratio [SIR] = 3.8, 95 percent confidence
      interval [CI] = 2.6-5.4) and to a lesser extent PM (SIR = 1.7, CI = 1.1-2.4).
      Significant excesses were observed for cancers of lung, ovary, and lymphatic and
      hematopoietic system. However, the excess cancer incidence declined steadily with
      increasing years since initial diagnosis of PM/DM. The cancer risk was increased
      about sixfold (SIR = 5.9, CI = 3.8-8.7) during the first year, but was lower
      during the second year (SIR = 2.5, CI = 1.1-4.8), with no significant excesses in
      subsequent years of follow-up. These findings confirm that PM/DM may occur as a
      paraneoplastic syndrome that calls for steps aimed at early cancer detection and
      treatment. Among long-term survivors of PM/DM, however, there is little evidence
      to warrant extensive preventive and screening measures beyond those recommended
      for the general population.

PMID- 7718741
TI  - One-bead-one-structure combinatorial libraries.
AB  - Combinatorial libraries employing the one-bead-one-compound technique are
      reviewed. Two distinguishing features characterize this technique. First, each
      compound is identified with a unique solid support, enabling facile segregation
      of active compounds. Second, the identity of a compound on a positively reacting
      bead is elucidated only after its biological relevance is established. Direct
      methods of structure identification (Edman degradation and mass spectroscopy) as
      well as indirect "coding" methods facilitating the synthesis and screening of
      nonpeptide libraries are discussed. Nonpeptide and "scaffold" libraries, together
      with a new approach for the discovery of a peptide binding motif using a "library
      of libraries," are also discussed. In addition, the ability to use combinatorial
      libraries to optimize initially discovered leads is illustrated with examples
      using peptide libraries.

PMID- 7718742
TI  - The use of light-directed combinatorial peptide synthesis in epitope mapping.
AB  - The application of light-directed combinatorial peptide synthesis to epitope
      mapping is described. Photolithography and solid phase peptide synthesis were
      combined in an automated fashion to assemble arrays containing 1024 peptide
      sequences on a glass support in ten steps with the precise location of each
      peptide known. The simultaneous synthesis of two slides containing three arrays
      of peptides each allowed for the independent screening of both a monoclonal
      antibody (mAb) and its Fab fragment at two different concentrations. A binary
      synthesis strategy was used to assemble the arrays, resulting in all deletions
      and truncations possible within the FLRRQFKVVT sequence being present and
      available for screening. The relative binding interactions of each peptide was
      determined by incubating the arrays with either mAb D32.39 and goat antimouse
      immunoglobulin G-FITC or mAb D32.39 Fab-FITC conjugate, followed by scanning the
      surface for fluorescence with an epifluorescence microscope. The fragment RQFKVVT
      was found to bind tightly to both the mAb and Fab fragment while tethered to the
      surface, and was measured to have 0.49 nM affinity in solution. The frame-shifted
      RRQFKVV sequence was found to have lower affinity both in solution (1.3 mM) and
      on the surface. The fragment RQFKVV was determined to be responsible for antibody
      recognition and was found to bind tightly when tethered to the surface, yet
      exhibited no binding in solution as the free acid, suggesting the requirement of
      an amidated C-terminus or an additional flanking residue. A deletion analysis
      revealed that the novel RQFKVT sequence exhibited higher affinity than the RQFKVV
      sequence while tethered to the surface.

PMID- 7718743
TI  - Novel biopolymers for drug discovery.
AB  - The solid phase synthesis and generation of libraries of "unnatural biopolymers"
      is described. These polymers are characterized by novel backbones and building
      blocks, the properties of which may modify their pharmacological and folding
      properties.

PMID- 7718744
TI  - A review of the utility of soluble peptide combinatorial libraries.
AB  - This paper reviews the preparation and use of soluble synthetic combinatorial
      libraries (SCLs) made up of millions of peptide and nonpeptide sequences for the
      identification of highly active individual compounds. First presented in 1991,
      SCLs have been prepared in a number of different lengths and formats, and are
      composed entirely of L-, D-, and unnatural amino acids. Also, existing peptide
      libraries have been chemically transformed to yield large diversities of
      nonpeptidic compounds. This review encompasses the published work from this
      laboratory using SCLs for the identification of antigenic sequences recognized by
      monoclonal antibodies, novel peptide agonists and antagonists to opioid
      receptors, new trypsin inhibitors, novel antibacterials, and compounds that
      inhibit melittin's hemolytic activity. SCLs offer a fundamental, practical
      advance in the study of interactions between peptide and nonpeptide sequences and
      their biochemical or pharmacological targets.

PMID- 7718745
TI  - Con: shed mediastinal blood should not be reinfused after cardiac surgery.

PMID- 7718746
TI  - An unusual cardiac mass shown by intraoperative transesophageal echocardiography.

PMID- 7718747
TI  - Effects of perioperative hemodynamic variations on mitral regurgitation.

PMID- 7718748
TI  - Left internal versus right internal jugular vein access to central venous
      circulation using the Seldinger technique.

PMID- 7718749
TI  - Double-lumen tubes--the final word?

PMID- 7718750
TI  - Propofol-fentanyl versus isoflurane-fentanyl anesthesia for coronary artery
      bypass grafting: effect on myocardial contractility and peripheral hemodynamics.
AB  - To avoid intraoperative awareness and postoperative respiratory depression from
      high-dose opioid anesthesia, propofol (P), or isoflurane (I) has been combined
      with moderate-dose opioid with varying results. However, the effects of both P
      and I on myocardial contractility and left ventricular afterload have not been
      completely quantified. The end-systolic pressure-diameter relationship (ESPDR) of
      the left ventricle (LV) is a reliable method to quantitatively assess LV
      contractility because it is relatively independent of changes in preload and
      incorporates afterload changes. The purpose of this study was to quantify the
      cardiodynamic effects of propofol-fentanyl (PF) anesthesia in comparison with
      isoflurane-fentanyl (IF) anesthesia in patients undergoing coronary artery bypass
      grafting (CABG). Thirty patients with normal or moderately impaired LV function
      (ejection fraction > or = 40% with LV end-diastolic pressure < or = 18 mmHg, no
      preoperative akinesia or dyskinesia) undergoing elective CABG were studied. After
      premedication with flunitrazepam, 2 mg orally, all patients were induced with
      thiopental, 1 mg/kg, fentanyl, 20 micrograms/kg, and vecuronium, 0.1 mg/kg, and
      were ventilated with oxygen/air (F(1)O2 0.6). Anesthesia was maintained
      throughout the procedure with a zero-order intravenous (IV) continuous infusion
      of P, 3 mg/kg/h (PF group), or with isoflurane inhalation of 0.6% (IF group),
      supplemented by intermittent boluses (5 micrograms/kg) of fentanyl (up to a total
      maintenance dose of 30 micrograms/kg). After intubation, a cross-section of the
      LV was visualized by two-dimensional transesophageal echocardiography and an m
      mode echocardiogram was obtained at the maximum anterior-posterior diameter. The
      radial artery pressure tracing and the ECG were simultaneously recorded with the
      M mode.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718751
TI  - Effects of phenylephrine or volume loading on right ventricular function in
      patients undergoing myocardial revascularization.
AB  - The acute effects of phenylephrine (PHE) administration or intravascular volume
      loading on right ventricular (RV) function were examined in 34 patients
      undergoing elective coronary artery surgery. After anesthetic induction with
      sufentanil and midazolam, 20 patients received PHE to treat hypotension and
      increase systemic arterial pressure 20% above baseline values. PHE effectively
      restored arterial pressure without changing stroke index (SI), although RV
      ejection fraction (RVEF) declined (41.3% to 37.6%) with concomitant increases in
      RV end-diastolic volume index (RVEDVI) (86.3 to 97.5 mL/m2) and RV end-systolic
      volume index (51.8 to 63.4 mL/m2). In the first 6 to 8 hours after surgery, 18
      patients received intravascular volume expansion with 5% albumin when the
      clinical perfusion state was inadequate and accompanied by pulmonary artery
      occlusion pressure (PAOP) less than 15 mmHg and a hemoglobin level greater than 8
      g/dL. Volume loading with 500 mL of albumin increased SI(27.0 to 31.8mL/m2), PAOP
      (12.2 to 15.4 mmHg) and RVEDVI (69.0 to 86.5 mL/m2), although RVEF declined
      (39.3% to 37.6%). Baseline values of RVEF and SI (but not PAOP or right atrial
      pressure [RAP]) were lower in 9 of 18 patients who exhibited declines in RVEF
      after volume loading, and RAP was a poor indicator of RVEDVI (r = 0.17). RVEDVI
      (but not RAP or PAOP) had significant correlation with SI during volume loading.
      There was no relationship between the presence of hemodynamically significant
      right coronary artery stenoses requiring revascularization or other perioperative
      factors with the response to PHE before revascularization or to volume loading
      after revascularization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718752
TI  - Comparison of propofol with isoflurane for maintenance of anesthesia in patients
      with chronic obstructive pulmonary disease: use of pulmonary mechanics, peak flow
      rates, and blood gases.
AB  - Patients with chronic obstructive pulmonary disease (COPD) are usually
      anesthetized with an inhalation agent. After Institutional Review Board approval,
      informed consent was obtained from 60 patients with moderate to severe COPD
      according to a preoperative severity scoring system, which took into account
      history and objective findings. By using objective criteria, such patients were
      randomly assigned to receive propofol (group I) or isoflurane (group II) as
      primary maintenance agents. Preoperative and postoperative arterial blood gases,
      peak expiratory flow rates (PEFR), and chest X-rays were compared. Total dynamic
      compliance (CDYN) and V1 (% volume exhaled in first second) were measured using
      Pitot tube sidestream spirometry. A 1,000-mL super-syringe was used to measure
      total static compliance (CST). Measurements were recorded postintubation,
      midanesthesia, and pre-extubation. All patients received fentanyl, lidocaine, and
      propofol, 1.5 to 2.0 mg/kg, for induction. Succinylcholine, 1-1.5 mg/kg, was
      administered to facilitate intubation. Maintenance was with N2O-O2, vecuronium,
      and either propofol (n = 30) or isoflurane (n = 30). Both groups showed decreases
      in postoperative PaO2, SaO2, and PEFR (p < 0.05), but there were no differences
      between groups (p > 0.05). There were no significant chest X-ray differences.
      There were no differences between groups with respect to intraoperative pulmonary
      mechanics (p > 0.05). The only difference between groups was an increase in
      postoperative PaCO2 in group I and a decrease in group II (p < 0.05). Use of
      Pitot tube sidestream spirometry is a practical and noninvasive technique for
      monitoring pulmonary mechanics during anesthesia.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7718753
TI  - Pathologic fibrin formation and cold-induced clotting of membrane oxygenators
      during cardiopulmonary bypass.
AB  - In 1,800 patients undergoing cardiac surgery over a 2-year period, 11 incidents
      of abnormal inlet pressure elevations occurred before the membrane oxygenators.
      In 3 patients, the oxygenators had to be changed during cardiopulmonary bypass.
      This complication was found to be caused by fibrin formation possibly secondary
      to precipitation of fibrinogen with other coagulation factors in the heat
      exchangers of the oxygenators during the cooling phase. Large amounts of fibrin
      were demonstrated in the heat exchanger of the oxygenators. After careful washing
      of the apparatus, plasmin was added and fibrin was detected by measuring D-dimer
      levels. In heat exchangers from uneventful operations, only trace amounts of
      fibrin were found. Because there were no cold agglutinins demonstrated in the
      patients before surgery, cryoprecipitation studies were performed soon after
      surgery. When the patients' plasma samples were studied at different
      temperatures, from 37 degrees C down to 3 degrees C, cryoprecipitates or a gel
      (in 1 patient only) were formed. This indicated that there might be something
      abnormal with regard to fibrinogen-fibrin formation. The study patients were
      therefore investigated after the acute phase of the operation had ended for
      various coagulation factors, as well as for fibrin gel network characteristics.
      The results were compared with those of a control group (n = 10) with uneventful
      operations. There were no differences between the groups with regard to levels of
      coagulation factors VII and VIII and von Willebrand factor, although they were
      increased in both groups. The mean levels of coagulation inhibitors, antithrombin
      and Protein S, were slightly lower in the study patients. All of these patients
      had a highly pathologic, ie, tight fibrin gel network, except for the patient in
      whose sample a gel formed, despite being treated with aspirin or oral
      anticoagulants. The network was also tighter in some of the controls (v middle
      aged reference individuals), although it was significantly tighter in the
      patients. It is concluded that some individuals who have an increased tendency to
      form tighter fibrin gel networks might be at increased risk for a severe
      complication during cardiac surgery performed under hypothermia.

PMID- 7718754
TI  - Cardiorespiratory response of intravenous angiotensin-converting enzyme inhibitor
      enalaprilat in hypertensive cardiac surgery patients.
AB  - Twenty-four patients undergoing elective coronary artery bypass surgery were
      studied. Either the angiotensin-converting enzyme (ACE) inhibitor enalaprilat,
      0.06 mg/kg, (n = 12), or saline solution (= control group; n = 12), was randomly
      and blindly administered intravenously when the mean arterial blood pressure
      (MAP) increased to 90 mmHg after induction of anesthesia. Cardiorespiratory
      parameters were studied before injection, during the subsequent 30 minutes,
      precardiopulmonary bypass (CPB), post-CPB, and at the end of surgery. MAP was
      significantly reduced 5 minutes after administration of enalaprilat. The peak
      reduction of blood pressure was observed after 30 minutes (from 98 +/- 4 to 68 +/
      8 mmHg). Even immediately before CPB (112 +/- 12 minutes after injection of
      enalaprilat), MAP and systemic vascular resistance were significantly lower than
      baseline values. Heart rate remained almost unchanged in both groups. Cardiac
      index increased slightly in the enalaprilat patients (maximum: +0.75 L/min/m2 20
      minutes after injection). Filling pressures (central venous pressure, pulmonary
      capillary wedge pressure) were also significantly reduced by enalaprilat. There
      were no differences from the control patients with regard to changes in right
      ventricular hemodynamics (right ventricular ejection fraction, right ventricular
      end-diastolic volume, right ventricular end-systolic volume), pulmonary gas
      exchange (PaO2), or intrapulmonary right-to-left shunting (Qs/Qt). VO2 increased
      only in the enalaprilat patients (from 179 +/- 28 to 230 +/- 30 mL/min) (p <
      0.05). Cardiorespiratory parameters did not differ between the two groups post
      CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718755
TI  - Left-sided stellate ganglion ablation or "rate-controlled" vagal nerve
      stimulation decreases regional myocardial metabolic impairment during acute
      ischemia in dogs.
AB  - This study was designed to see whether during ischemia a metabolic advantage
      results with left-sided ablation of the stellate ganglion (SGA), an available
      clinical technique. Its effects on hemodynamics and regional metabolism during
      myocardial ischemia were compared with those of electrical stimulation of the
      left vagus nerve (VS), a nonclinical technique, and those of a control condition
      (ischemia without intervention). The left anterior descending coronary artery
      (LADa) of 30 dogs was constricted to reduce blood flow by 50% and then 75% from
      that before constriction and after autonomic intervention (baseline).
      Electrocardiogram, left-ventricular (LV) first-time derivative (dP/dt), and
      systemic, LADa, and LV end-diastolic pressures were continuously recorded. Before
      and during each constriction, cardiac output and regional myocardial blood flow
      (by microspheres), blood gas tensions, pH, hemoglobin O2 saturation, lactate,
      glucose, sodium, and potassium concentrations were measured. During ischemia, SGA
      and VS each decreased heart rate, myocardial contractility (dP/dt), and filling
      pressures, the decrease in each variable being greater with VS. Also during
      ischemia, myocardial O2 delivery and consumption decreased to the same extent in
      the ischemic zone with VS, but the O2 delivery/consumption ratio was higher only
      with SGA. In addition, ischemic lactate production was lower with SGA and VS than
      with no autonomic intervention. It is concluded that left-sided SGA or VS to a
      heart rate of 80 to 90 beats per minute similarly mitigated metabolic impairment
      during myocardial ischemia. Although the study was only designed to compare
      modification of ischemia by two different techniques, the results suggest that
      ischemic zone O2 delivery/consumption ratio and hemodynamic stability were better
      with SGA.

PMID- 7718756
TI  - High-frequency ventilation with a conventional anesthetic ventilator during
      cardiac surgery.

PMID- 7718757
TI  - Abdominal aortic aneurysmectomy in a patient with bilateral renal
      autotransplants.

PMID- 7718758
TI  - Mitral valve prosthesis reoperation via right anterolateral thoracotomy
      complicated by postoperative blindness.

PMID- 7718759
TI  - Use of sufentanil and atracurium anesthesia in a patient with acute porphyria
      undergoing coronary artery bypass surgery.

PMID- 7718760
TI  - Acute platelet-rich plasmapheresis for cardiac surgery.

PMID- 7718761
TI  - Case 1-1995. Anesthetic management for resection of a giant pulmonary
      arteriovenous malformation.

PMID- 7718762
TI  - Evaluation of hepatic venous flow using transesophageal echocardiography in
      coronary artery bypass surgery: an index of right ventricular function.
AB  - Hepatic venous flows (HVFs) were evaluated to assess right-heart function by
      transesophageal Doppler echocardiography in 45 patients undergoing coronary
      artery bypass graft (CABG) surgery. Peak velocity and time velocity integral of A
      wave (reverse flow in end diastole), S-wave (forward flow in systole), V-wave
      (reverse flow in late systole), and D-wave (forward flow in diastole) of biphasic
      HVF were examined. Peak systolic-diastolic ratio (S/D) of biphasic HVF and
      reverse flow ratio (% reversal flow/forward flow [RF/FF]) of both biphasic and
      monophasic HVF also were examined. Tricuspid regurgitation (TR) was assessed by
      color Doppler image. All data were obtained after performing the following:
      induction of anesthesia (stage 1); pericardiectomy (stage 2); cardiopulmonary
      bypass (CPB) (stage 3); and closure of sternum (stage 4). HVFs at stage 1 were
      obtained in all 45 patients, and the peak S/D in patients with a history of
      inferior wall myocardial infarction (MI) was significantly less than that in
      patients without a history of MI (p < 0.05). HVFs of 35 patients were recorded
      successfully at all stages. In 5 of these 35 patients, HVF patterns became
      monophasic after CPB, and only one of those patients had severe TR. In the rest
      of the 30 patients with biphasic patterns throughout the operation, peak A and D
      velocities increased (p < 0.01), whereas peak S and V velocities decreased (p <
      0.01) after CPB compared with those before CPB. Consequently, peak S/D was
      reduced (p < 0.01), and %RF/FF increased (p < 0.05). These post-CPB changes were
      associated with increased (p < 0.01) pulmonary artery diastolic and right atrial
      pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718763
TI  - Pro: shed mediastinal blood retransfusion should be used routinely in cardiac
      surgery.

PMID- 7718764
TI  - Biology of blood progenitor cells used in transplantation.
AB  - Blood progenitor cells (BPC) are increasingly used in a variety of clinical
      settings. These include autologous and allogeneic transplantation after
      myeloablative therapy, and gene therapy. The optimal blood products for each of
      these applications have not been defined. The use of different cytotoxic drugs
      and cytokines, alone and in combination, results in the mobilisation of different
      total numbers and relative proportions of primitive and committed BPC. Some
      cytotoxics and cytokines not only are poor at mobilising BPC, but also are
      myelotoxic. Here we review the biology of BPC mobilisation and its implications
      for their clinical use.

PMID- 7718765
TI  - Prevalence of the myelodysplastic syndromes in Japan.
AB  - To determine the prevalence of the myelodysplastic syndromes (MDS) in Japan, we
      conducted a nationwide survey in 1991. The survey included the sex, birth date
      and type of MDS of the patients from all (n = 2315) hospitals with 200 beds or
      more and 188 hospitals randomly selected from 7526 hospitals (1/40) with 199 beds
      or less. The point prevalence of MDS was estimated to be almost 3000 as of
      September 1, 1991, and it was 3.4 per 100,000 men of 15 years old or older and
      2.1 per 100,000 women of 15 years old or older. Refractory anemia (RA) was most
      common (51%) followed by RA with excess of blasts (RAEB; 18%) and RAEB in
      transformation (RAEB-t; 14%). RAEB, RAEB-t and chronic myelomonocytic leukemia
      (CMML) showed a high male/female ratio (3.0 or higher) although the sex ratio of
      other types was almost 1.0.

PMID- 7718766
TI  - Effect of orotic acid on TGF-beta 1-induced growth inhibition of L1210 leukemic
      cells.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) exerted growth-inhibitory effect
      on L1210 leukemic cell line, manifested by the decrease in viable and increase in
      dead cells. The cell death evoked by TGF-beta 1 was both necrotic and apoptotic,
      quantified by the trypan blue exclusion method and apoptotic index, respectively.
      The induction of programmed cell death by TGF-beta 1 was confirmed by gel
      electrophoresis of DNA, where the characteristic 'DNA ladder' resulting from the
      internucleosomal DNA cleavage was visualized. The enhancement of cell mortality
      by TGF-beta 1 was associated with the inhibition of ornithine decarboxylase (ODC)
      expression (measured by the reverse transcriptase-polymerase chain reaction
      method) and impaired activity of this key enzyme in polyamine synthesis. Orotic
      acid (OA)--a known tumor promoter--stimulated proliferation of L1210 leukemic
      cells and diminished the necrotic effect of TGF-beta 1, but it did not change the
      extent of apoptosis evoked by TGF-beta 1. OA increased the expression of ODC and
      diminished depressional influence of TGF-beta 1 on transcription and activity of
      ODC in leukemic cells. IN CONCLUSION: OA is a bioactive compound stimulating the
      growth of leukemic cells and diminishing the growth-inhibitory effect of TGF-beta
      1. ODC gene is probably one of the targets for both OA and TGF-beta 1 influences
      in L1210 leukemic cells.

PMID- 7718767
TI  - Monoclonal integration of HTLV-1 in pleural effusion cells in a seropositive
      patient with tuberculous pleuritis.
AB  - The pleural effusion of a 79-year-old man who was a carrier of human T-cell
      leukemia virus type 1 (HTLV-1) showed monoclonal growth of HTLV-1 infected T
      cells. While the integration pattern of HTLV-1 was polyclonal in the peripheral
      blood mononuclear cells, it was monoclonal in the infiltrated cells of the
      pleural effusion. Morphologically atypical lymphoid cells were also found in the
      peripheral blood and in the pleural effusion. The pleural effusion disappeared
      after treatment with antituberculous drugs. The nature of the monoclonal
      proliferation of HTLV-1 infected T-lymphocytes is discussed.

PMID- 7718768
TI  - Acute promyelocytic leukemia developed in a patient with congenital antithrombin
      III deficiency.
AB  - A case of acute promyelocytic leukemia (APL) developed in a patient with
      congenital antithrombin III (AT-III) deficiency is reported. Despite the presence
      of disseminated intravascular coagulation (DIC), plasma AT-III activity was not
      decreased at the diagnosis of APL compared to the patient's baseline level
      (approximately 50% of normal). He was successfully treated with all-trans
      retinoic acid (ATRA) to achieve complete remission without the use of heparin.
      Although he developed phlebitis at the site of insertion of the intravenous
      catheter during remission-induction, no major thrombotic episode was noted.
      Coagulation parameters including fibrin and fibrinogen degradation products (FDP
      E), thrombin-antithrombin complex (TAT), FDP-D dimer (D-D dimer), and plasmin
      alpha 2 plasmin inhibitor complex (PIC) improved rapidly after initiation of
      ATRA. This case is a clear demonstration of the characteristics of DIC developing
      in APL, i.e. no or minimal decrease in the level of AT-III activity and a
      predominant increase in the fibrinolytic system, rather than hypercoagulability.

PMID- 7718769
TI  - Allogeneic peripheral blood stem cell transplantation for treatment of induction
      failure in a patient with Philadelphia chromosome-positive acute lymphoblastic
      leukemia.
AB  - We report a successful case of allogeneic peripheral blood stem cell
      transplantation (PBSCT) for the treatment of primary induction failure in acute
      lymphoblastic leukemia (ALL). The patient was a 46-year-old male with Ph-positive
      ALL and failed to achieve complete remission (CR). His HLA genotypically
      identical brother refused to donate bone marrow. Instead, PBSCs were collected by
      apheresis from the brother after administration of G-CSF at a dose of 10
      micrograms/kg. For allogeneic PBSCT, the patient was conditioned with marrow
      ablative chemotherapy and received the PBSC harvest containing 7.8 x 10(4)/kg of
      CFU-GM, 1.8 x 10(6)/kg of CD34-positive cells and 2.7 x 10(8)/kg of T
      lymphocytes. After transplant, the neutrophil count exceeded 0.5 x 10(9)/l on day
      16 and the platelet count exceeded 20 x 10(9)/l on day 22. CR was confirmed with
      tri-lineage engraftment in bone marrow samples on days 28 and 49; disappearance
      of the Ph-chromosome was documented. Sustained engraftment was also confirmed
      cytogenetically using a variable number of tandem repeat (VNTR) markers. Acute
      graft-vs.-host disease did not develop with conventional prophylaxis of
      methotrexate and cyclosporine. However, on day 85 the patient developed leukemia
      relapse and died on day 97. This clinical trial suggests that allogeneic PBSCT
      may be an alternative to allogeneic bone marrow transplantation in some limited
      situations.

PMID- 7718770
TI  - [HIV: a risk for interventional radiologists?].

PMID- 7718771
TI  - [Rontgen's discovery].

PMID- 7718772
TI  - [Echo contrast agents for the color Doppler sonographic diagnosis of deep femoral
      venous thrombosis].
AB  - PURPOSE: Evaluation of an echo contrast medium (Echovist) for color-coded duplex
      sonography of deep venous thrombosis of the thigh. MATERIAL AND METHODS: In 19
      patients with deep vein thrombosis of the thigh, diagnosed by contrast
      phlebography, 22 color-coded duplex sonography studies were performed for flow
      analysis at the top of the thrombus. During the studies 8.5 ml echo contrast
      medium were injected in an ipsilateral vein at the back of the foot. The flow
      signals of the non-enhanced color coded duplex sonography were compared with
      those of the echo enhanced study for differentiation between floating thrombi
      from those adherent to the vein wall. RESULTS: The echo-enhanced color-coded
      duplex sonography showed a significant increase in detection of perfusion at the
      top of the thrombus in comparison with non-enhanced color-coded duplex sonography
      (p < 0.01). 9 thrombi were regarded as wall adherent after the native study, 7 of
      these could be identified as floating thrombi by echo-enhanced color-coded duplex
      sonography. CONCLUSION: Echo-enhanced color-coded duplex sonography yields a
      significant increase of diagnostic information in certain findings of the non
      enhanced color-coded duplex sonography differentiating between floating thrombi
      and wall adherent thrombi in the deep venous system of the thigh.

PMID- 7718773
TI  - [CT compared with SPECT in chronic recurrent pulmonary embolism: hyperdensities
      as signs of pulmonary artery hyperperfusion?].
AB  - Purpose of this study was to assess the aetiology of inhomogeneous lung
      parenchymal attenuation in patients with chronic pulmonary thromboembolism,
      presenting as sharply demarcated areas of increased and decreased density on
      computed tomography. MATERIAL AND METHODS: In 52 patients with chronic pulmonary
      thromboembolism, computed tomography (CT) was compared with perfusion
      scintigraphy (including SPECT) and agreement was assessed: "good" (all hyperdense
      CT segments are perfused on scan), "moderate" or "poor" (one or two resp. three
      or more hyperdense CT segments are not perfused). RESULTS: 44 of the 52 patients
      showed an inhomogeneous pulmonary attenuation on CT. Correlation of hyperdense
      areas with perfused lung parenchyma was graded as "good" in 26 cases, "moderate"
      in 14 and "poor" in 4 cases. In 40 of these 44 patients, scintigraphy revealed
      additional perfusion defects in homogeneously lucent areas on CT. In 6 of 8
      patients with entirely homogeneous lung density on CT, SPECT revealed perfusion
      defects. CONCLUSION: In patients with chronic pulmonary thromboembolism,
      increased lung density on CT is caused by hyperperfused lung parenchyma distally
      to patent pulmonary arteries. SPECT proves to be more sensitive in diagnosing
      perfusion inhomogeneities.

PMID- 7718774
TI  - [The initial results of spiral CT angiography in demonstrating stenoses of the a.
      carotis].
AB  - PURPOSE: To determine the value of spiral CT angiography in Maximum Intensity
      Projection (MIP)-technique for evaluation of carotid artery stenosis. METHODS: A
      comparison of the MIP technique with intraarterial DSA was done in 24 patients
      with 40 stenoses. Quantification of stenosis was determined according to the
      NASCET study: mild (0-29%), moderate (30-69%), severe (70-99%) and occlusion
      (100%). RESULTS: Totally the correlation of spiral CT angiography with DSA was
      80% (r = 0.93; p = 0.0001). In the moderate stenosis group (r = 1; p = 0.1573),
      severe stenosis group (r = 0.89; p = 0.002) and the occlusion group (r = 1; p =
      0.0009) there was a good correlation with DSA. In the mild stenosis group (r =
      0.55; p = 0.0704) correlation of spiral CT angiography with DSA was poor. Spiral
      CT angiography allows an excellent delineation of calcifications. Tandem lesions
      and collateral flow cannot be shown with spiral CT angiography. CONCLUSION:
      Intraarterial DSA remains the gold standard for evaluation of carotid artery
      stenosis, because DSA is the modality which shows the whole length of the carotid
      artery and yields information on tandem lesions and collateral flow.

PMID- 7718775
TI  - [The facial nerve in the petrous bone in thin-layer paratransverse and sagittal
      magnetic-resonance-tomographic T1-spin-echo and FLASH images].
AB  - PURPOSE: It is difficult to effect visualization and delineation of the facial
      nerve and its neighbouring structures in the temporal bone with conventional MRI
      examination protocols. We tested temporal bone MRI with 2 mm slices and compared
      T1-weighted FLASH (TR = 400 ms, TE = 10 ms, 90 degrees flip angle) and spin-echo
      (TR = 540 ms, TE = 15 ms) sequences. PATIENT AND METHODS: 5 volunteers and 14
      patients were examined with the head coil of a 1.0T whole body MRI scanner
      (Impact, Siemens, Erlangen) with para-transversal images orientated parallel to
      the inferior outline of the clivus and sagittal images orientated along the
      brainstem. RESULTS: The facial nerve and its neighbouring structures could be
      reliably visualized and differentiated along its entire course. The FLASH
      sequence was superior to the spin-echo sequence. 8 of 11 patients with peripheral
      facial nerve palsy showed contrast enhancement. In two patients, local swelling
      of the affected facial nerve was evident. CONCLUSION: The MRI technique tested
      here seems promising for temporal bone examinations.

PMID- 7718776
TI  - [A comparison of NMR tomography and arthrography in functional disorders of the
      temporomandibular joint].
AB  - PATIENTS AND METHODS: 31 patients with clinically diagnosed dysfunction of the
      temporomandibular joint (TMJ) were examined by magnetic resonance imaging (MRI;
      1.5 Tesla, TR/TE 600/30) in closed and open mouth position and functional
      arthrography with digital image recording. RESULTS: Both methods agreed in the
      evaluation of the disc position. In 23 joints with displaced disc reposition was
      found in 11 cases and in 14 cases using MRI or arthrography, respectively. MRI
      proved to be superior in the diagnosis of sideways disc rotations. Joint
      hypermobility, eccentric disc displacement (n = 4) and perforation (n = 3) were
      shown by functional arthrography. Due to the good demonstration of osseous,
      muscular and discoligamentous structures, MRI as a noninvasive imaging modality
      is the method of choice for TMJ evaluation. Arthrography can be advantageous in
      complex functional disturbances or if MRI and clinical findings are inconclusive.
      The clinical diagnosis of disc displacement was found to be accurate in only 68%
      of the cases.

PMID- 7718778
TI  - [NMR tomographic measurement of femoral ante-torsion and tibial torsion].
AB  - PURPOSE: A new MRI method for the measurement of femoral torsion and tibial
      torsion is presented. METHODS: Axial images were generated using a standard
      gradient echo sequence (FLASH 2D). Otherwise measurement of femoral and tibial
      torsion was performed according to an established CT method. RESULTS: The torsion
      angles measured using MRI were in accordance with the angles measured using the
      CT method. The MRI method was not more time-consuming than the CT method.
      CONCLUSION: In respect of radiation exposure, MRI determination of femoral and
      tibial torsion should be considered particularly in children and patients who
      have to undergo repeated torsion measurements.

PMID- 7718777
TI  - [The measurement of the femoral torsion angle in children by NMR tomography
      compared to CT and ultrasound].
AB  - PURPOSE: Anteversion of the femoral neck was measured by MRI in 19 children (37
      hips) preoperatively before femoral rotation osteotomies. MATERIAL AND METHODS:
      The results of this new technique were compared with values for anteversion
      obtained by CT and ultrasound. The measurements were performed independently by
      two observers to determine the correlation between the three different methods
      and to assess their reliability. RESULTS: It was possible to show a high
      correlation coefficient (Pearson) between MRI and CT (r = 0.77) as well as MRI
      and sonography (r = 0.81). The mean angles obtained by CT (34 degrees, range +5
      to +82 degrees) and ultrasound (25.6 degrees, range +10 to +40 degrees) appeared
      larger than the MRI values (mean angle 23.2 degrees, range 0 to +65 degrees),
      which can be explained by the different measurement techniques. Mean inter- and
      intra-variability was low for MRI (r = 0.97 and r = 0.97) and CT (r = 0.99 and r
      = 0.96) but slightly higher for sonography (r = 0.88 and r = 0.88). MRI is a new
      reliable and precise method to evaluate femoral anteversion that does not require
      ionising radiation. CONCLUSION: MRI is recommended for preoperative planning of
      paediatric femoral rotation osteotomy patients.

PMID- 7718779
TI  - [The percutaneous CT-guided treatment of osteoid osteomas: a combined procedure
      with a biopsy drill and subsequent ethanol injection].
AB  - PURPOSE: The purpose of this study was the clinical evaluation of a percutaneous
      treatment modality in patients with an osteoidosteoma. PATIENTS AND METHODS: 6
      patients with an osteoidosteoma of the upper (n = 1) and lower (n = 5) extremity
      which were confirmed on plain film radiographs and computed tomography underwent
      CT controlled drill biopsy of the nidus with subsequent injection of 96% ethanol
      into the biopsy channel to sclerose probably remaining remnants of the nidus. The
      procedure was started under local anaesthesia, but drilling of the nidus was
      carried out under a short general anaesthesia using ketamine. RESULTS: The
      intervention was successful in all patients. No postinterventional infection
      occurred and no recurrence was observed in any of the patients in a follow-up
      time between 0.5 and 2 years. CONCLUSION: Although only 6 patients were treated
      until now, we conclude that this combined procedure using a bone biopsy system
      and the subsequent injection of alcohol is a safe and successful procedure for
      percutaneous treatment of osteoidosteoma.

PMID- 7718780
TI  - [Percutaneous treatment possibilities in thrombotic occlusion of Brescia-Cimino
      dialysis shunts].
AB  - PURPOSE: Acute thrombotic occlusion of Brescia-Cimino forearm fistulae is a
      severe complication. Aspects of percutaneous therapy include balloon dilatation,
      thrombolysis and mechanical thrombectomy. We report on 21 cases with obstructed
      shunts. Clinical evaluation and palpation helped to select each shunt for an
      individual therapeutic approach. PATIENTS AND METHODS: One patient presented with
      a proximal arterial occlusion, three patients with a small occluding thrombus, 4
      patients with a severe stenosis but only a small amount of thrombus and 13
      patients with an extended amount of clot material. RESULTS: 7 patients underwent
      balloon dilatation alone, three patients thrombolysis with rtPA and 11 patients
      hydrodynamic thrombectomy. Arterialized shunt flow was reestablished in 20 of 21
      cases. The shunt was reused for dialysis in 17 cases. Reobstruction within two
      weeks after intervention occurred in two cases. CONCLUSIONS: With regard to the
      individual clot size, different percutaneous methods are available for successful
      shunt recanalisation.

PMID- 7718781
TI  - [The identification of unknown corpses by x-ray comparison].
AB  - Between 1987 and 1993, 30 unknown bodies were identified by means of pre- and
      postmortem radiographs at the Forensic Institute in Mainz. Our experience
      indicates that radiological identification comprises a useful, rapid and cheap
      method, at least as valuable as dactyloscopy or odontological comparisons. The
      ages of available radiographs were up to 25 years; the most suitable regions are
      the skull (11), pelvis and lumbar spine (6), lower femur and knee (5) and distal
      leg with the ankle joint (5). In respect of the problem of objectifying the
      probability of identity, possibilities for solutions are shown.

PMID- 7718782
TI  - Transvenous liver biopsy with the radial jaw forceps in patients with non
      correctable coagulopathy.

PMID- 7718783
TI  - [Rotational angiography of the renal arteries].

PMID- 7718784
TI  - [A positioning frame for the cinematic NMR tomography of the cervical spine].

PMID- 7718785
TI  - [The cholegraphic effect of iopentol].

PMID- 7718786
TI  - [Infrarenal aortic occlusion on the spiral CT].

PMID- 7718787
TI  - [Aortocaval fistula--a rare complication of an aortic aneurysm].

PMID- 7718788
TI  - MR findings in mullerian duct cysts.

PMID- 7718789
TI  - [The occlusion of a large aneurysm of the a. iliaca communis with a coated metal
      stent].

PMID- 7718790
TI  - [Microcirculation in pial vessels of the ischemized rat brain during opioid
      lymphostimulation].

PMID- 7718791
TI  - [Quantitative change in the hepatocyte dehydrogenase activity in system
      endotoxemia].

PMID- 7718792
TI  - [Comparative histophotometric characteristics of the structural-metabolic
      heterogeneity of hepatocytes in peritonitis and gangrene of the extremities].

PMID- 7718793
TI  - [Effects of neurotropin in pain syndromes].

PMID- 7718794
TI  - [Participation of central H-cholinoreceptors in preventing respiration damping
      upon activation of the GABA-ergic system of the brain].

PMID- 7718795
TI  - [Involvement of GABA- and H-cholinergic receptor systems in forming terminal
      respiration].

PMID- 7718796
TI  - [The effect of adaptation to moderate physical loads on the increase in
      resistance of the isolated heart to ischemia and successive reperfusion].

PMID- 7718797
TI  - [The role of glycolysis in maintaining the energy-synthesizing function of rat
      hepatocytes adapted and not adapted to hypoxia at various oxygen concentrations].

PMID- 7718798
TI  - [A non-actomyosin component of thermally-induced contraction of the vascular wall
      in hypertension].

PMID- 7718799
TI  - [The lipophilic antioxidant U-18 and superoxide dismutase prevent destruction of
      cultured hippocampal neurons during hypoxia and in the post-hypoxic period].

PMID- 7718800
TI  - [Effect of carnosine on lipoxygenase activity in rabbit reticulocytes].

PMID- 7718801
TI  - [Decrease in the level of lipid peroxidation and acute bromobenzene activity upon
      administering a polymeric form of zinc metallothionein to mice].

PMID- 7718802
TI  - [Level of substances reacting with 2-thiobarbituric acid in murine blood plasma
      in acute ethanol poisoning during protection with zinc metallothionein].

PMID- 7718803
TI  - [Gastroprotective effect of zinc sulfate in ethanol ulcer formation in rats].

PMID- 7718804
TI  - [A water-soluble form of estradiol with estrogenic and cardiotropic activity].

PMID- 7718805
TI  - [Early protection of animals, immunized by a recombinant plague vaccine, from
      experimental plague].

PMID- 7718806
TI  - [Comparative characteristics of specific binding of estradiol-17beta with
      proteins-receptors in CBA and C57Bl/6 murine line uterine cytosol during
      sarcomagenesis induced by 1,2-dimethylhydrazine].

PMID- 7718807
TI  - [Immunoglobulins from a tumor-bearing body as possible regulators of the growth
      rate of relapses and metastases of Ehrlich carcinoma].

PMID- 7718808
TI  - [Activity of the fin-system of artificially formed cointegrated plasmids
      pAP42/pRSF2124 and pAP42/pUB781].

PMID- 7718810
TI  - [Differential repair activity of human chromosomes].

PMID- 7718809
TI  - [The role of reversible phosphorylation in genetically determined polymorphism by
      brain tryptophan hydroxylase activity].

PMID- 7718811
TI  - [Use of osteogenic cells--bone marrow precursors--for reparative osteogenesis in
      the lower jaw of experimental animals].

PMID- 7718812
TI  - [Individual variation of immune response to thyroid hormones in BALB/c mice].

PMID- 7718813
TI  - [Recombinant strains of Escherichia coli providing a high level of expression of
      human interleukin-3 and interleukin-4].

PMID- 7718814
TI  - [Comparative morphometric and informative analysis of changes in various sections
      of the pancreas after binding it].

PMID- 7718815
TI  - [Evaluation of the synchronicity of electrical activity of various sections of
      the gastrointestinal tract by peripheral electrography].

PMID- 7718816
TI  - [The effect of dimethyl sulfate on the structure and cytoarchitectonics of rat
      thymus].

PMID- 7718817
TI  - Assessing the use of computers in industrial occupational health departments.
AB  - Computers are widely used in business and industry and the benefits of
      computerizing occupational health (OH) departments have been advocated by several
      authors. The requirements for successful computerization of an OH department are
      reviewed. Having identified the theoretical benefits, the real picture in
      industry is assessed by surveying 52 firms with over 1000 employees in a large
      urban area. Only 15 (29%) of the companies reported having any OH service, of
      which six used computers in the OH department, reflecting the business priorities
      of most of the companies. The types of software systems used and their main use
      are examined, along with perceived benefits or disadvantages. With the decreasing
      costs of computers and increasingly 'user-friendly' software, there is a real
      cost benefit to be gained from using computers in OH departments, although the
      concept may have to be 'sold' to management.

PMID- 7718818
TI  - A comparison of some of the characteristics of patients with occupational and non
      occupational asthma.
AB  - Occupational asthma is the most frequently diagnosed occupational lung disease
      reported to the SWORD (Surveillance of Work-related and Occupational Respiratory
      Disease) scheme. However, diagnosing occupational asthma is not straightforward,
      and establishing a link with work may be difficult. This study was undertaken to
      determine the differences between patients with occupational asthma and those
      with non-occupational asthma which might help in their diagnosis. Information was
      collected using a self-completed questionnaire. Questionnaires were distributed
      to 30 subjects aged 18-65 years at each of two clinics--one for patients with
      occupational asthma and one for those with cryptogenic and environmental asthma.
      Replies were received from 26 patients with occupational asthma (87%) and 29
      patients with non-occupational asthma (97%). The age of onset was significantly
      higher for those with occupational asthma (42.6 vs 20.7 years). Significantly
      more subjects with occupational asthma reported improvement on holiday, whereas
      no significant difference was found in the numbers reporting worsening of
      symptoms on work days. Those with occupational asthma were less likely to report
      seasonal variation in symptoms, exacerbation by allergies, pets and stress, or a
      family history of asthma. Subjects with occupational asthma were more likely to
      become unemployed (50% vs 3%). Recognition of some of these features in a
      patient's history may help in the difficult task of differentiating occupational
      from non-occupational asthma, potentially avoiding the need for exhaustive
      investigations in some patients. The high prevalence of holiday improvement among
      subjects with non-occupational asthma suggested that domestic or environmental
      allergies arising outside the workplace may have been making an important
      contribution to ongoing symptoms in these subjects.

PMID- 7718819
TI  - What is this life...?

PMID- 7718820
TI  - Effective occupational health--difficulties of delivery.

PMID- 7718821
TI  - Urinary 1-hydroxypyrene: a biomarker for polycyclic aromatic hydrocarbon exposure
      in coal liquefaction workers.
AB  - This study was undertaken to assess the suitability of urinary 1-hydroxypyrene (1
      OHPyr) as a biological marker of polycyclic aromatic hydrocarbon (PAH) exposure
      in coal liquefaction workers. This is believed to be the first evaluation of the
      method in coal liquefaction workers. Ten workers were selected from a group of 30
      workers considered likely to be at risk of contamination from PAHs by virtue of
      their jobs. Spot urine samples were collected at the start of a work period and
      at the end of each work shift, with analysis of 1-OHPyr being undertaken by high
      performance liquid chromatography linked to a fluorescence detector. Exposure was
      assessed by the completion of questionnaires. Excretion of 1-OHPyr increased
      significantly over the working period, and there was a significant increase in 1
      OHPyr where start-shift and end-shift samples were taken over one shift. A
      significant decrease in 1-OHPyr was found during breaks away from work.

PMID- 7718823
TI  - Audit of pre-employment assessments by occupational health departments in the
      National Health Service.
AB  - Pre-employment health assessment of applicants to the National Health Service
      (NHS) is one of the functions of occupational health departments in the NHS. This
      paper describes the results of a process and outcome audit of this activity,
      concentrating on the current practice of occupational health departments. The
      audit was carried out by 40 NHS occupational health units who provided
      information on a standard questionnaire on all pre-employment assessments
      undertaken over a three-month period. This produced 9139 questionnaire returns.
      The analysis showed that the most common method of assessment was the use of a
      self-administered questionnaire alone (49.4%). A self-administered questionnaire
      followed by a nurse interview as standard practice was the next most common
      method (34.1%), but referral to a physician was uncommon. The outcome of the
      assessments for 98% of all applicants was 'fit for work'. A total of 120
      individuals (1.3%) were assessed as 'fit to work, but with some restriction' and
      65 individuals (0.7%) were considered 'unfit'. The most common reasons for
      rejection were abnormal body mass index (40%), skin conditions (21.5%) and
      psychiatric conditions (10.8%). The most common reasons for restriction were
      musculoskeletal conditions (27.5%), skin conditions (15%) and abnormal body mass
      index and psychiatric conditions (both 10.8%). The audit identified wide
      variation between occupational health departments in the NHS in the practice of
      restriction and rejection. A decision on the value of pre-employment assessment
      in the NHS mus take into consideration the ability of the process to achieve its
      aim, the time and manpower involved in the process, and the probability of low
      restriction and rejection rates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718822
TI  - Polypropylene production and colorectal cancer: a review of the epidemiological
      evidence.
AB  - Polypropylene has been produced for over 35 years and has a wide variety of
      applications including industrial uses, food packaging and many domestic uses. As
      a high-molecular-weight polymer, polypropylene is considered chemically inert
      with little or no physiological or toxicological effects. Nevertheless, early
      epidemiological studies of polypropylene production workers and carpet
      manufacturing employees who use polypropylene reported a significant excess of
      colorectal cancer. In one study, five of the seven cases were diagnosed within a
      five-month period, and in the other study, five cases were diagnosed within an 18
      month period. Recent updates of these two study populations have found no
      continuation of the excess of colorectal cancer, thereby indicating that the
      earlier observations on these two groups reflected the chance nature of a time
      space cluster. Moreover, investigations of polypropylene production workers in
      the United States, Germany, Australia and the United Kingdom found no association
      with colorectal cancer. When the results of all studies of polypropylene
      production workers are pooled, the summary risk ratio for colorectal cancer is
      1.37 (95% confidence interval 0.83-2.11). Taken together, the epidemiological
      evidence and the absence of toxicological data do not support a causal
      association between polypropylene and colorectal cancer.

PMID- 7718825
TI  - Salmon farming: occupational health in a new rural industry.
AB  - The medical hazards of salmon farming can be grouped into those related to marine
      safety, fish husbandry, fish-farm diving and disease treatments. The hostile
      water environment requires thermal protection and personal buoyancy aids as
      workers frequently fall in the water from boats or cages. Feedstuffs may generate
      respirable dust and attract rats, creating a risk of leptospirosis. Musculo
      skeletal injuries are common from lifting nets. Fish-farm diving has particular
      risks which can be minimized. Organophosphorous pesticides are used to treat sea
      lice and employees require health surveillance. Fish immunization is required to
      reduce the incidence of Aeromonas salmonitica. Needlestick injuries when using
      oil-based vaccines are a serious hazard to employees. The occupational health
      problems of salmon farming are predictable and preventable with primary safety
      measures. This new industry is safer than land-based agriculture on current
      evidence.

PMID- 7718824
TI  - Occupational injuries in Alberta: responding to recent trends.
AB  - General patterns of injury in the Alberta workplace are reflected in figures from
      the Workers' Compensation Board, which reliably enumerates acute injuries but not
      necessarily chronic musculoskeletal conditions. Roughly one-quarter of these
      injuries are to the back and neck. The absolute number of injuries is of interest
      in terms of the overall problem of injury in the workplace, but the rate of
      injury is used to set priorities for intervention among industries. The injury
      rate identifies industries at greatest risk given the size and activity of their
      workforce. Using rates, industries can be classified as high or low risk. Over
      time, claim rates for the major industrial sectors have been fairly stable. Rates
      from 1987 and 1988 were used in setting provincial government initiatives to
      control injury frequency and severity and are examined in this report.
      Construction is clearly a high-risk industry. It involves many trades and
      operations that have an inherently high risk. The situation is different for the
      manufacturing sector. This also has a very high injury experience. However,
      unlike construction, the risk is concentrated in one sub-industry-meat and
      poultry packing. As a single sector, oil and gas has a low risk. When the
      industry is broken down into its component functions, however, the oil and gas
      exploration, drilling and servicing components are clearly out of line with the
      rest of the sector. Risk is highly concentrated in these sub-industries. Data
      from Alberta confirm that smaller employers generally have a higher injury risk
      than larger employers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718826
TI  - Human parvovirus B19 infection in healthcare workers.
AB  - This paper reports the occurrence of human parvovirus B19 infection in seven
      healthcare workers in an acute hospital. The clinical presentation mimicked that
      of rubella and the diagnosis was made by the detection of human parvovirus B19
      IgM antibody in blood samples taken from the affected members of staff. The paper
      discusses the importance of accurate diagnosis of B19 infection because this
      virus has been implicated in causing or exacerbating a variety of medical
      conditions. B19 infection may be serious for people with chronic haemolytic
      anaemias, those who are immunocompromised or those who are pregnant. B19
      infection in pregnancy may be a cause of hydrops fetalis, particularly if the
      infection occurs during the second trimester. This is in contrast to the risk of
      intra-uterine rubella infection which is maximal in the first few weeks of
      pregnancy and which affects fetal development. The paper highlights the need for
      guidelines for occupational health practitioners on the management of parvovirus
      B19 infection and the need to make healthcare workers aware of the importance of
      this infection.

PMID- 7718827
TI  - What do doctors mean by tenosynovitis and repetitive strain injury?
AB  - Confusion exists in both the scientific and the lay press on the meaning of the
      terms tenosynovitis and repetitive strain injury. The courts are increasingly
      being asked to make judgements on individual cases but this gives little in the
      way of guidance to doctors producing reports for the Department of Social
      Security or solicitors. The aim of this study was to document what such doctors
      mean by these terms, what diagnostic criteria they use, and to make any necessary
      recommendations. The diagnostic criteria for DSS industrial conditions A8
      (tenosynovitis) and A4 (professional cramp) varied greatly and what the experts
      understood by the term 'repetitive strain injury (RSI)' was so variable that the
      term is meaningless. Half of the doctors who responded felt that there was no
      genuine organic condition corresponding to their assessment of what the term
      means. As half of the doctors providing reports believe that 'repetitive strain
      injury' is not a genuine disease entity and the other half do, court cases will
      continue. The dilemma appears to be that completely different meanings are
      ascribed to the same term. Therefore, the term 'repetitive strain injury' should
      no longer be used.

PMID- 7718828
TI  - Tuberculosis trends in eastern Europe and the former USSR.
AB  - The aim of this paper is to assess trends in tuberculosis morbidity and mortality
      in the countries of Eastern Europe and the former USSR. Data on morbidity and
      mortality were obtained from reports of the Ministries of Health, a 1992 WHO
      questionnaire, national tuberculosis associations, and other sources. The quality
      of surveillance of tuberculosis cases differs widely between countries. Ranging
      from 19 to 80 per 100,000 population in 1990-1992, tuberculosis notification
      rates of most Eastern European and former USSR countries are higher than those of
      Western European countries. The lowest tuberculosis notification rate is reported
      in the Czech Republic, while the highest are reported in Romania and Kazakhstan.
      While in Albania, Croatia and Slovenia notification rates have continued to
      decline, in the remaining countries of Eastern Europe the declining trend has
      recently stopped. Nevertheless, countries such as the Czech Republic, Hungary,
      Poland and the Slovak Republic have experienced a distinct rate decrease when the
      3-year average rate around 1985 is compared to that around 1990, despite the very
      recent levelling-off or increase. In Romania, the previous decline in
      notification rate ended in 1985 and in the period 1986-1992 an average 5.4%
      annual increase was observed. In this country, two-thirds of all cases still
      occur among young adults. Among the Baltic countries of the former USSR, the
      declining trend continues in Estonia, whereas in Latvia and Lithuania
      notification rates decreased less markedly from 1985 to 1990 than in the first
      half of the 1980s. Among the other European countries of the former USSR, Russia
      and Ukraine had a slow decline in the first half of the 1980s and a more
      pronounced one from 1985 to 1990. During the latter period of time, in Belarus
      and Moldova the decrease has been steeper. In the Caucasian countries of the
      former USSR, where underreporting and low case-finding are recognized, case rates
      have stabilized in Armenia, while in Azerbaijan and Georgia there was a decrease
      from 1985 to 1990. Among the Asian countries of the former USSR, Kazakhastan and
      Tajikistan reported a lower decline in case rates from 1985 to 1990 than from
      1980 to 1985. Kyrgyzstan, Turkmenistan, and Uzbekistan reported increases in
      notification rates from 1985 to 1990: in Turkmenistan an average 5.5% annual
      increase in rate was observed between 1987 and 1991. Tuberculosis mortality is
      steadily increasing in Romania, Armenia, Kyrgyzstan, Latvia, Lithuania, Moldova,
      and Turkmenistan, while no decline is seen in most of the other countries of
      Eastern Europe and the former USSR.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7718829
TI  - Tuberculosis case-finding in Nicaragua: evaluation of routine activities in the
      control programme.
AB  - SETTING: The new International Union against Tuberculosis and Lung Disease
      (IUATLD) tuberculosis strategy developed in the 1980s in Tanzania, Malawi and
      Mozambique, was simultaneously implemented in Nicaragua. OBJECTIVE: Present
      results of case-finding, identify trends in incidence and limitations in case
      finding and reporting. DESIGN: Data are based upon the traditional reporting
      system until 1987, replaced as the programme was reorganized. Data were also
      collected directly from the Central Laboratory, Programme and Laboratory
      registers during supervision of health centres. RESULTS: Quality control of
      sputum smears shows 1.8% discordance between peripheral and central laboratories.
      Notification rate of smear-positive tuberculosis declined 1.7% yearly 1983-1991
      and 2.6% for all cases. Half of the patients are new smear-positive pulmonary
      cases, 40% smear-negative pulmonary cases. Relapses represent 11-13% of all smear
      positive patients, children 7-30% of all cases. One-third of extrapulmonary
      tuberculosis cases are pleural effusions, another third lymphadenitis. 41% of
      adult patients entered as smear-negative in the programme had no smear reported
      in the laboratory. CONCLUSIONS: Quality control of sputum smears was established
      and the reporting system improved in spite of adverse conditions. Notification
      rate declined gradually. Smears should be done in all patients classified as
      smear-negative pulmonary tuberculosis.

PMID- 7718830
TI  - Trend in tuberculous meningitis in Barcelona in children aged 0-4 years:
      correlation with the annual risk of tuberculous infection.
AB  - SETTING: All the paediatric hospitals in the province of Barcelona. OBJECTIVE: To
      examine the trend in the incidence of tuberculous meningitis (TM) in children
      aged 0-4 years and its correlation with the annual risk of tuberculous infection.
      DESIGN: Survey conducted between 1975 and 1991. RESULTS: 157 cases of TM in
      children aged 0-4 years were diagnosed between 1975 and 1991. A constant decrease
      during the prospective period is observed from 21 cases of TM in 1977 to only 2
      cases in 1991 with an annual decrease of 5.5%, which is smaller than the 8%
      annual decrease of the annual risk of tuberculous infection. A close correlation
      between the observed incidence of TM and the average annual risk of infection to
      which children in the same area were exposed r = 0.9156 (P < 0.0001) is verified.
      Moreover, this correlation gets even closer when considering the annual risk of
      infection as a percentage of the TM incidence, since a stable correlation of
      about 1% (0.89-1.39%) is demonstrated. Nevertheless, the incidence and the number
      of observed cases of TM is twice that expected if one refers to the Table that
      calculates meningitis cases by means of the annual risk of infection. We observed
      one case of TM among 218-384 infected children, i.e. a risk of developing TM of
      0.19-0.26%, higher than that found in the countries with the most favourable
      tuberculosis situations. The sharp decrease of TM coincides with the suppression
      of BCG-vaccination in Barcelona, which suggests that it has not substantially
      changed the decrease of the risk of developing TM in children under 5 years of
      age. The decrease in the annual risk of infection, and consequently TM, is
      essentially due to the improvement of treatment in adults. CONCLUSION: It is
      confirmed that the incidence of TM in children under 5 years represents 1% of the
      annual risk of infection. The TM incidence thus permits the determination of the
      annual risk of infection when the conditions to calculate it directly do not
      exist.

PMID- 7718831
TI  - Tuberculous pericarditis in Tanzanian patients with and without HIV infection.
AB  - SETTING: Large academic medical center in Tanzania. OBJECTIVES: To determine the
      etiologies and outcomes of large pericardial effusions in HIV-infected and
      uninfected patients. DESIGN: Prospective cohort study of patients admitted with
      new large pericardial effusions, confirmed echocardiographically. Patients had
      pericardial biopsies and drainage with extensive analysis of tissue and fluid
      specimens, and were followed with clinical and echocardiographic examinations.
      RESULTS: Of 28 patients with large pericardial effusions, 19 were infected with
      HIV-1. 22 had invasive diagnostic procedures: 14 of 14 HIV-infected patients, but
      only 4 of 8 non-HIV-infected patients, had tuberculous pericarditis (P = 0.01).
      All but 1 of the HIV-infected patients had strongly positive tuberculin skin
      tests, and short-term outcomes were similar in the 2 groups. CONCLUSION: TB is
      the predominant cause of large pericardial effusion in HIV-infected patients in
      this setting; non-HIV-infected patients are more likely to have other etiologies.
      These patients were at an early stage of HIV infection and responded well to
      treatment. In settings where microbiological studies are not routinely available,
      HIV-infected patients with large pericardial effusions may be treated empirically
      for tuberculosis and monitored for improvement. If improvement does not follow
      within 2-4 weeks further studies are indicated. HIV-negative patients should
      undergo diagnostic evaluation initially.

PMID- 7718832
TI  - Insertion sequence typing of Mycobacterium tuberculosis: characterization of a
      widespread subtype with a single copy of IS6110.
AB  - DNA fingerprinting with the insertion sequence IS6110 (also known as IS986) has
      become established as a major tool for investigating the spread of tuberculosis.
      Most strains of Mycobacterium tuberculosis have multiple copies of IS6110, but a
      small minority carry a single copy only. We have examined selected strains from
      Malaysia, Tanzania and Oman, in comparison with M. bovis isolates and BCG strains
      carrying one or two copies of IS6110. The insertion sequence appears to be
      present in the same position in all these strains, which suggests that in these
      organisms the element is defective in transposition and that the loss of
      transposability may have occurred at an early stage in the evolution of the M.
      tuberculosis complex.

PMID- 7718833
TI  - Procoagulant activity of PPD-stimulated human lymphocytes after cryopreservation.
AB  - OBJECTIVE: Human mononuclear cells from a previously sensitized donor generate
      procoagulant activity (PCA) following stimulation with purified protein
      derivative (PPD). Lymphocytes of tuberculous pleural effusions are also highly
      responsive to PPD stimulation. We examined the influence of cryopreservation on
      lymphocytes following stimulation with PPD. DESIGN: Peripheral blood lymphocytes
      of 5 healthy PPD skin test positive subjects were incubated with either PPD,
      thromboplastin, or concanavalin A (Con A) at concentrations of 0, 1, and 10
      micrograms/ml. PCA was determined by measuring the recalcification time. Tests
      were repeated following cryopreservation for 4 weeks. RESULTS: Incubation of
      fresh lymphocytes led to a dose dependent shortening of recalcification time: PPD
      (0-1-10 micrograms/ml: 100-84-65%), thromboplastin (0-1-10 micrograms/ml: 100-85
      62%), and Con A (0-1-10 micrograms/ml: 100-85-42%). These results were highly
      reproducible when tests were repeated 6 weeks later. Cryopreservation did not
      significantly affect the expression of PCA following incubation with PPD and with
      thromboplastin. In contrast, cryopreservation significantly diminished the degree
      of Con A generated PCA. CONCLUSION: Cryopreservation and storage of human
      lymphocytes is possible without alteration of PCA expression following their
      incubation with PPD or thromboplastin.

PMID- 7718834
TI  - Cognitive and affective reactions of black urban South Africans towards
      tuberculosis.
AB  - SETTING: The core concepts of tuberculosis (TB) control programmes are case
      finding (voluntary presentation) and case-holding (compliance for both patient
      and system). Voluntary presentation and compliance are complex behaviours that
      depend upon symptom recognition and evaluation, cultural and social influences
      and enabling factors such as time, money, skills and appropriate/accessible
      health services. It was hypothesised that cognitive and affective reactions
      towards TB were based on perceived prevalence, perceived seriousness and
      perceived social stigma. OBJECTIVES: To ascertain the underlying dimensions that
      are used when people react cognitively and emotionally to TB, and to determine
      possible restricting social influence factors on voluntary presentation and case
      holding. DESIGN: A questionnaire was designed to obtain information on background
      details, perceptions of TB (transmission, prevention, diagnosis and treatment),
      and a 19-item cognitive/affective scale. 19 trained interviewers administered the
      questionnaire. Interviews were conducted with 487 black adults (67 TB patients on
      ambulatory therapy and 420 non-TB community members), from two urban townships in
      the Transvaal, South Africa. RESULTS: The majority of respondents were aware of
      the infectious nature of TB, that it could be cured and the length of treatment.
      The most problematic issues were isolation for TB sufferers and the harm TB
      sufferers do to others. Cognitive/affective reactions were similar for TB
      patients and community members. 10 items out of the 19-item cognitive/affective
      scale had communality estimates > or = 0.30. 3 factors were extracted. The first
      factor seemed to combine personal threat (high personal and family risk) with
      social rejection by the immediate family and community for TB sufferers. Factor 2
      had strong overtones of social stigma, with its emphasis on dirt, poverty and
      poor nutrition. Factor 3 rejected alcohol and tobacco consumption as causal
      agents of TB. CONCLUSIONS: The predominant cognitive/affective reactions towards
      TB were personal threat, social rejection and social stigma, providing partial
      support for the hypothesis. The powerful force of social rejection and social
      stigma cannot be underestimated. These inhibiting factors require urgent
      attention to improve voluntary presentation and compliance behaviour.

PMID- 7718835
TI  - Cerebral tuberculosis in the immunocompetent host: 8 cases observed in
      Switzerland.
AB  - 8 cases of cerebral tuberculosis were observed between January 1985 and June 1993
      at the University Hospitals of Lausanne and Geneva, Switzerland. 5 patients were
      foreigners and 3 were Swiss, 2 of them alcoholics. All patients were HIV
      seronegative. Mycobacterium tuberculosis was isolated in 7 patients and M. bovis
      in one patient. All patients had radiological or bacteriological signs of
      pulmonary tuberculosis, and 3 had miliary tuberculosis. 3 patients died, 5 were
      cured. The main prognostic factors were age and the degree of neurological
      impairment at the beginning of treatment. The epidemiological, clinical,
      diagnostic and therapeutic aspects of this rare and severe form of extrapulmonary
      tuberculosis are reviewed.

PMID- 7718836
TI  - Small and sure wins the race.

PMID- 7718837
TI  - Tuberculous meningitis in France in 1990.

PMID- 7718838
TI  - Tuberculosis programmes: fragmentation or integration?

PMID- 7718839
TI  - Impact of the HIV epidemic on trends in tuberculosis in Abidjan, Cote d'Ivoire.
AB  - SETTING: West African capital city with excellent, population-based notification
      of tuberculosis cases during a decade with a rapidly emerging HIV epidemic.
      OBJECTIVE: To evaluate the impact of the HIV epidemic on tuberculosis in Abidjan,
      Cote d'Ivoire. DESIGN: Review of data on all cases of tuberculosis registered in
      the city in alternate years from 1981 to 1991 and calculation of population-based
      rates using census data. Also, systematic study of HIV seroprevalence among
      tuberculosis patients in 1989 and 1991. RESULTS: In 1981, several years before
      any health consequences of HIV were discernible in Abidjan, the incidence of
      tuberculosis was 155 per 100,000. By 1991, the rate of tuberculosis among HIV
      seronegative persons had decreased by 38% to 96 per 100,000; however, 43.6% of
      tuberculosis patients were HIV-infected, and the incidence of tuberculosis among
      HIV-infected persons was 1104 per 100,000 (relative risk 11.5, 95% CI 10.8-12.3),
      yielding an overall observed incidence of tuberculosis of 159 per 100,000
      population. The population attributable risk of tuberculosis due to HIV infection
      increased from 36% to 40% between 1989 and 1991. CONCLUSIONS: The HIV epidemic
      has reversed the expected steep decline in tuberculosis in Abidjan over the past
      decade, and the impact of HIV infection on the incidence of tuberculosis may be
      accelerating.

PMID- 7718840
TI  - Trend of HIV infection in patients with pulmonary tuberculosis in south India.
AB  - SETTING: Tuberculosis is life threatening, transmissible and pandemic especially
      among millions of HIV infected persons. In developing countries like India where
      HIV infection is becoming prevalent and where tuberculosis infection has long
      been endemic, its incidence is increasing. OBJECTIVE: The aim of the study was to
      find out the trend of HIV infection in patients with pulmonary tuberculosis in
      south India. DESIGN: HIV seropositivity was assessed in 1430 radiologically
      and/or bacteriologically confirmed pulmonary tuberculosis patients attending
      major tuberculosis institutions in Madras by the AIDS Cell, Institute of
      Microbiology, Madras Medical College, Madras from January 1991 to May 1993.
      RESULTS: HIV seropositivity was found to rise significantly from 0.77% in 1991 to
      3.4% in 1993 (P < 0.05). 22 (91.67%) of a total of 24 HIV seropositive pulmonary
      tuberculosis patients had pulmonary cavities and 21 patients (87.5%) had
      bacteriological confirmation of tuberculosis. CONCLUSION: The findings of this
      prospective study suggest that pulmonary tuberculosis patients with HIV infection
      are an in early phase of immunosuppression. This study reveals the rising trend
      of HIV infection; all persons with tuberculosis should therefore be questioned
      about the risk factors for HIV infection and urged to have an HIV test.

PMID- 7718841
TI  - Prevalence of tuberculosis in a rural area by an alternative survey method
      without prior radiographic screening of the population.
AB  - SETTING: Mass miniature radiography (MMR) is the usual tool for population
      screening in tuberculosis case prevalence surveys. However, this facility is not
      available at most centres in India. OBJECTIVE: The feasibility of conducting a
      survey without MMR screening was therefore investigated. DESIGN: The study was
      carried out in Bangalore rural district during 1984-1986. The area was the same
      as for six earlier prevalence surveys conducted since 1961. The population aged
      up to 44 years was tuberculin tested. Persons with test induration size of > or =
      10 mm were eligible for sputum examination, besides all those aged over 45 years
      who were eligible without discrimination. RESULTS: Reduction of workload was not
      adequately achieved through screening, as 78.4% of the registered population
      (29,400) was still eligible for sputum examination. The changed screening
      procedure in this survey also made comparison with earlier data difficult. In
      spite of more liberal and comprehensive screening, the observed prevalence rate
      of cases (438/100,000 population aged 10+ years) was similar to earlier surveys.
      The prevalence rate of smear-positive cases, however, was much lower (68/100,000
      population aged 10+ years). CONCLUSION: In conclusion, the candidate screening
      procedure was not suitable. The findings nevertheless conformed to the overall
      declining trend for the area, as reported earlier.

PMID- 7718842
TI  - Short-course chemotherapy for tuberculous pleural effusion and culture-negative
      pulmonary tuberculosis.
AB  - SETTING: Chest Clinics at Blackburn and Newham, UK. OBJECTIVE: To test the
      efficacy of a short-course regimen of 6 months rifampicin and isoniazid
      supplemented by 2 months initial pyrazinamide (2HRZ-4HR), in the treatment of
      smear and culture-negative pulmonary tuberculosis and tuberculous pleural
      effusion in routine clinical practice. DESIGN: The results of 152 patients with
      these forms of tuberculosis treated between 1981 and 1991 were analysed
      retrospectively. RESULTS: 127 patients, 65 with pleural effusion and 62 with
      culture-negative pulmonary tuberculosis, completed treatment as planned. 100 were
      followed up for a mean duration 20.5 months (range 4-72) for culture-negative
      disease and 14.6 months (range 3-46) for pleural effusion. There were no
      relapses, giving a relapse rate of 0% (95% confidence interval 0-3.62%).
      CONCLUSION: Unsupervised self-administered treatment with 2HRZ/4HR is a highly
      effective regimen for culture-negative pulmonary tuberculosis and tuberculous
      pleural effusion in service conditions.

PMID- 7718844
TI  - Abdominal tuberculosis in Taiwan: a report from Veterans' General Hospital,
      Taipei.
AB  - SETTING: From 1986 to 1992, 27 cases of abdominal tuberculosis were diagnosed in
      Veterans General Hospital-Taipei, Taiwan, including 21 cases of intestinal
      tuberculosis and 6 cases of peritoneal tuberculosis. OBJECTIVE: To ascertain the
      clinical characteristics of abdominal tuberculosis in Chinese patients and the
      possibility of early clinical diagnosis of abdominal tuberculosis. DESIGN:
      Clinical features, diagnosis and treatment modality of these 27 cases were
      reviewed. RESULTS: 22 of the patients (81.5%) had chest X-ray evidence of
      pulmonary tuberculosis. Only 2 had normal chest X-ray findings. Sputum
      mycobacterium culture was positive in 14 of 27 patients (51.9%). 20 patients
      received exploratory laparotomy for the diagnosis and all of the preoperative
      diagnoses were wrong. The diagnosis was still incorrect or uncertain in 9 cases
      after laparotomy if no pathological examination was done. Ileocecal area was the
      most common site of intestinal tuberculosis in our series and 3 of 11 ulcerative
      types of intestinal tuberculosis died later. CONCLUSION: Due to protean
      manifestations, the diagnosis of abdominal tuberculosis was frequently
      misdiagnosed, and particularly as carcinomatosis. The diagnosis should be
      considered when patients with pulmonary tuberculosis suffer from abdominal
      discomfort. Exploratory laparotomy is needed in cases suspected of abdominal
      carcinomatosis without definite diagnosis.

PMID- 7718843
TI  - The influence of BCG immunization on tuberculin reactivity in healthy Chilean
      women in the third trimester of pregnancy.
AB  - SETTING: Tuberculin testing is an accepted method for screening pregnant women
      for tuberculosis. The interpretation of tuberculin reactivity in bacillus
      Calmette-Guerin (BCG)-immunized pregnant women is still in debate. OBJECTIVE:
      Four related issues were addressed: (1) The effect of pregnancy on tuberculin
      reactivity; (2) the effect of age differential on tuberculin reactivity; (3) the
      effect of repeated immunization with BCG; and (4) the risk of developing
      tuberculosis during pregnancy or a 3-year post-partum period. DESIGN: We
      performed tuberculin testing in 840 healthy Chilean women in the 32nd to 34th
      week of pregnancy; 807 had been immunized with 1 or more doses of BCG. There were
      3 age groups: 177 were < or = 19 years old, 534 were 20-29 years old, and 129
      were > or = 30 years old. All women in the study were followed at least 3 years
      post-partum. RESULTS: Women < or = 19 years old and non-pregnant women of similar
      age studied in the same geographical area had a similar distribution of the size
      of tuberculin reactions. Over 50% of all BCG-immunized women in each group had
      tuberculin reactions > or = 10 mm. A differential effect of different doses of
      BCG was significant only in 20- to 29-year-old women. None of the women in this
      study developed tuberculosis during pregnancy or a 3-year post-partum observation
      period. CONCLUSIONS: Healthy, BCG-immunized pregnant women may have positive
      tuberculin reactions without having an increased risk for tuberculosis. The
      incidence of tuberculosis and the BCG immunization status need to be considered
      in the development of policy recommendations for diagnosis and treatment of
      Mycobacterium tuberculosis infection in pregnant women.

PMID- 7718845
TI  - Silicotuberculosis: long-term outcome after short-course chemotherapy.
AB  - SETTING: A medical facility for approximately 90,000 gold miners employed on 24
      South African gold mines. OBJECTIVE: To establish the long-term risk attributable
      to silicosis of relapse from pulmonary tuberculosis treated with short-course
      chemotherapy. DESIGN: A consecutive sample of gold miners with pulmonary
      tuberculosis allocated to receive rifampicin, isoniazid, pyrazinamide and
      streptomycin given on weekdays for 5 months. Radiographs were assessed at the
      time of diagnosis for the presence of silicosis. All of the men were followed for
      at least 5 years after completing their treatment, or until they left mine
      service or suffered a relapse of tuberculosis. RESULTS: The sample included 549
      men of whom 167 had silicosis. The incidence density for relapse in silicosis was
      1.55 (95% CI 0.97, 2.48) times that for the men without silicosis. There was no
      difference in the pattern of relapse over time between the two groups: the mean
      period to relapse in the men with silicosis was 2.6 years (SD 1.89 years) and for
      the men without silicosis was 3.1 years (SD 2.23 years) (P = 0.6). CONCLUSION:
      Silicosis causes a small increase in the risk of relapse of tuberculosis.
      Relapses in both groups were not confined to the first 2 years after completion
      of treatment.

PMID- 7718846
TI  - Acute respiratory infections in children: a community-based study comparing a
      primary health center and a pediatric unit, Republic of Guinea.
AB  - OBJECTIVE: A community-based study was carried out in the Republic of Guinea in
      order to evaluate the frequency of occurrence, severity of illness, risk factors
      and the results of planned treatment of acute respiratory infections (ARI) in
      children under the age of 15 years. DESIGN: The study was performed over a 1-year
      period in 2 distinct areas, 1 rural and 1 urban. A total of 2622 ARI were
      identified among children under 15 years of age. In the rural area, data were
      collected by primary health-care workers and by 2 physicians who were trained to
      supervise the study. RESULTS: Among the rural population, 1422 ARI were
      identified. In the city center, Conakry, 1200 ARI were identified in one
      children's hospital. The child population under 5 years of age was significantly
      greater in the rural area (95.2%) than in the city center (83.2%) (P < 0.0001).
      Malnutrition affected 10.6% of all the children. There were discrepancies in
      symptoms and signs affecting the 2 groups but the severity scores, including
      children under 5 years of age, were not significantly different: including
      children under 5 years of age, were not significantly different: 10-11% of the
      children were considered to have severe disease and 6.2% required urgent referral
      to hospital. Upper and lower respiratory infections (URI and LRI) were equally
      represented (49.9% and 50.1% respectively). Distribution of each type of ARI was
      significantly different in the 2 groups: there were significantly more URI in the
      city center, especially tonsillitis. Bronchitis and bronchopneumonia occurred
      significantly more often in the rural area. Pneumonia and bronchopneumonia
      represented 9.8% of all ARI. Use of antibiotic therapy was known in 2557
      patients: 1268 URI and 1289 LRI. In children with URI, 69.7% did not receive
      antibiotic therapy, 29.9% received 1 antibiotic and 0.03% received 2 antibiotics
      successively. Children from the city center received significantly more
      antibiotics than in the rural health center. In children with LRI, 17.8% did not
      receive antibiotic therapy, 81.7% received 1 antibiotic and 0.05% received 2
      antibiotics successively. There was no significant difference between the 2
      centers in antibiotic prescription. Clinical outcome showed that 93% of children
      were considered to be cured at day 7 and 99.4% at day 14. 14 children with severe
      pneumonia died. The infection cost (antibiotics plus other drugs prescribed as
      supportive care) was 0.45 US$ per child in the rural area and 9.7 US$ in the
      children's hospital. CONCLUSION: This supervised study constitutes the first
      large longitudinal study concerning respiratory infections in West Africa. It
      demonstrates that simple guidelines are valid in order to prevent mortality and
      complications. Care appropriate to population requirements in term of infectious
      diseases can be delivered with low cost and low technology.

PMID- 7718847
TI  - Genetic differences between BCG substrains.
AB  - SETTING: University-affiliated Mycobacteriology Reference Laboratory. OBJECTIVE:
      To determine the genetic differences of 25 BCG isolates representing 16
      referenced substrains. DESIGN: Non-randomized, observational study based on the
      visual comparison of the large restriction fragment (LRF) patterns created by
      digesting each BCG isolate's DNA with an infrequent cutting restriction
      endonuclease (DraI, AsnI, XbaI or SpeI) and separating the resultant DNA
      fragments with pulsed field gel electrophoresis. RESULTS: The 25 BCG isolates
      gave 13 different DraI LRF patterns, 11 different XbaI LRF patterns, 11 different
      AsnI LRF patterns, and 15 different SpeI LRF patterns. Examples of the same BCG
      substrains from different sources produced the same LRF patterns for only 2 of 6
      substrains studied. These findings suggest a significant degree of genetic
      diversity in this group of isolates despite a common origin. Four clinical BCG
      isolates gave LRF patterns identical to BCG Tice, BCG Connaught or BCG Glaxo. The
      BCG LRF patterns more closely resembled patterns of Mycobacterium bovis than M.
      tuberculosis. CONCLUSIONS: LRF patterns can accurately identify specific BCG
      substrains and will be useful in epidemiologic studies, monitoring vaccine
      production and studies of BCG vaccine efficacy.

PMID- 7718848
TI  - Therapeutic effect of KRM-1648 with various antimicrobials against Mycobacterium
      avium complex infection in mice.
AB  - A new benzoxazinorifamycin, KRM-1648 (KRM), was studied for its therapeutic
      efficacy in combination with other antimicrobials against Mycobacterium avium
      complex infections in mice. When M. intracellulare-infected (intravenously) mice
      were given KRM, clarithromycin (CAM), sparfloxacin (SPFX), or ethambutol (EB)
      each alone or in combination, by gavage, once daily 6 times per week
      (streptomycin [SM] was given subcutaneously twice per week) from day 1, KRM + CAM
      exhibited combined efficacy in terms of reducing the incidence of gross lung
      lesions and the bacterial loads in the lungs and spleens. The addition of either
      EB or EB + SPFX to KRM + CAM increased the efficacy. Moreover, the multi-drug
      regimen of KRM + CAM + EB + SPFX or ofloxacin [OFLX]) was more efficacious than
      rifampicin (RMP) + CAM + EB + SPFX (or OFLX). In M. avium infection, KRM +
      clofazimine was the most efficacious among two-drug combinations tested followed
      by KRM + SM. KRM + CAM was considerably less effective against M. avium than
      against M. intracellulare infection. KRM + EB and KRM+OFLX failed to show such a
      combined effect.

PMID- 7718849
TI  - Dysregulation of homeostasis of blood T-lymphocyte subpopulations persists in
      chronic multibacillary pulmonary tuberculosis patients refractory to treatment.
AB  - DESIGN: The dysregulation of homeostasis of blood-T lymphocyte subpopulations was
      studied in 21 cases of chronic, multibacillary pulmonary tuberculosis refractory
      to treatment. The clinico-bacteriological and immunological parameters studied in
      these cases (Gr A) were compared with those of a group of 10 newly-diagnosed drug
      sensitive cases of pulmonary tuberculosis (Gr B) at the beginning of the study
      and after 3 months of chemotherapy for tuberculosis. The chronic cases were
      treated with drugs selected from a reserve line. 10 normal healthy individuals
      were included in this study as a control group. RESULTS: At the beginning of the
      study the mean CD4/CD8 lymphocyte ratios in the refractory cases (0.69) and the
      newly diagnosed cases (0.81) were significantly lower than those of the normal
      control subjects (1.84). After 3 months of chemotherapy all but 3 of the newly
      diagnosed cases showed clinical improvement, and all became sputum-negative.
      Their CD4/CD8 ratio recorded a rise to near normal (1.54). On the contrary,
      following 3 months of reserve-line regimen, only 7 of the 21 group A cases showed
      sputum conversion. In all of the refractory cases, irrespective of sputum
      conversion, the CD4/CD8 ratio remained low (1.05). CONCLUSION: This probably
      indicates that due to a long-standing bacillary load in drug resistant pulmonary
      tuberculosis patients the dysregulation of homeostasis of blood-T lymphocytes
      becomes persistent. This in turn delays their clinical and immunological
      recovery, even when therapy is adequate.

PMID- 7718850
TI  - Feasibility study of a district tuberculosis control programme with an 8-month
      short-course chemotherapy regimen utilizing the integrated health service network
      under field conditions in Nepal.
AB  - SETTING: Tuberculosis in Nepal has not been controlled; there is an annual risk
      of infection of more than 2%, a cure rate of 30-40% and a casefinding rate of
      40%. The necessity of a pilot programme with short-course chemotherapy that could
      be applied across the nation was discussed, and an operational research project
      utilizing the existing basic health service network was launched. OBJECTIVE: The
      main objective was to assess the feasibility of integrating a tuberculosis
      programme into the basic health services under various field conditions, and of
      introducing an 8-month short-course chemotherapy regimen instead of the 12-month
      standard regimen. DESIGN: A tuberculosis control programme package based on the
      current international strategy was introduced in Dhading and Chitawan districts
      (population 650,000) in 1990. The reported results were confirmed by central
      supervision and a follow-up study. RESULTS: 454 new smear-positive cases were
      found in the first year. 69% were cured and 9% completed their treatment. However
      an 85% completion rate could be expected from the results of the follow-up study.
      CONCLUSION: An integrated tuberculosis control programme with short-course
      chemotherapy is feasible. An adequate supply of drugs and supervision are vital
      components. The results showed the possibility of achieving the international
      target of an 85% cure rate and 70% detection, even within the constraints of the
      field conditions in Nepal.

PMID- 7718851
TI  - The use of sputum induction for establishing a diagnosis in patients with
      suspected pulmonary tuberculosis in Malawi.
AB  - SETTING: There has been a marked increase in notified cases of smear-negative
      pulmonary tuberculosis in Malawi since 1986. One reason for this may be related
      to the difficulties of getting adequate samples of expectorated sputum from
      patients. Sputum induction with nebulized hypertonic saline may be a simple way
      of obtaining a better specimen. OBJECTIVE: To examine the value of sputum
      induction for detecting cases of smear-positive tuberculosis. DESIGN: Sputum
      induction was performed on 82 adults presenting to the Queen Elizabeth Central
      Hospital, Blantyre, Malawi with clinically suspected pulmonary tuberculosis who
      were expectorated sputum smear-negative or unproductive of sputum. The induced
      sputum smear was examined for acid-fast bacilli and cultured for mycobacteria.
      RESULTS: Sputum was successfully induced from 73 of the 82 patients (26
      previously smear-negative and 47 previously unproductive). The induced sputum was
      smear-positive in 18 patients (5 previously smear-negative and 13 unproductive).
      Cultures were positive for Mycobacterium tuberculosis in the 18 smear-positive
      patients and a further 12 that had been smear-negative. 94 cases of smear
      positive pulmonary tuberculosis were notified during the study period. 18 (19%)
      were as a result of sputum induction. CONCLUSION: Sputum induction is a useful
      technique for improving the case detection rate of smear-positive tuberculosis in
      Malawi.

PMID- 7718852
TI  - Acute eosinophilic pneumonia in a patient infected with the human
      immunodeficiency virus.
AB  - A 24-year-old man infected with the human immunodeficiency virus (HIV) developed
      cough and progressive dyspnea over a period of 4 weeks. Absolute blood eosinophil
      count was 3360/mm3. Chest X-ray revealed alveolointerstitial infiltrates in both
      lower lobes. Eosinophilia was also found in bronchoalveolar lavage fluid. The
      clinical picture improved dramatically with steroids. Other causes of acute
      eosinophilic pneumonia were excluded.

PMID- 7718853
TI  - Tuberculosis presenting as a solitary splenic tumour.
AB  - A 48-year-old male had suffered from body weight loss and general malaise for 2
      months. Abdominal computed tomography showed a dilated intrahepatic duct with
      stones and a hypodense nodular mass in the spleen. A splenectomy and distal
      pancreatectomy were performed under the preoperative impression of a malignancy.
      Histological examination of the specimens revealed tuberculosis.

PMID- 7718854
TI  - Transthoracic (percutaneous) fine needle aspiration cytology diagnosis of
      pulmonary tuberculosis.
AB  - OBJECTIVE: The present study was carried out to assess the utility of
      transthoracic (percutaneous) fine needle aspiration (FNA) cytology in the
      diagnosis of pulmonary tuberculosis. DESIGN: During a period of 6 years (1985
      90), 202 ultrasound and computerized tomography (CT)-guided transthoracic FNA of
      pulmonary lesions were performed. Review of smears available in 190 cases
      revealed 38 (20%) cases of pulmonary tuberculosis. Age of the patients ranged
      from 11 months-75 years with a median of 40 years. The common clinical diagnoses
      were malignancy (14 cases), tuberculosis (8 cases) and pneumonitis (7 cases). The
      sites of FNA were lungs in 36 cases and pleural based lesions in 2 cases.
      RESULTS: Epithelioid granuloma without necrosis (type 1 reaction) were observed
      in 4 (10.5%) cases. Epithelioid granuloma with necrosis (type 2 reaction) and
      necrosis without epithelioid granuloma (type 3 reaction) were seen in 17 (44.7%)
      cases each. The overall rate of AFB positivity was 45.8%. The rate of acid-fast
      bacilli (AFB) positivity in type 1, 2 and 3 reactions were 0%, 38.5% and 60.0%
      respectively. CONCLUSION: This study shows that transthoracic (percutaneous) FNA
      is a useful means for diagnosis of pulmonary tuberculosis, especially when the
      clinical and/or radiological features are non-specific or point towards
      malignancy rather than tuberculosis.

PMID- 7718855
TI  - Do beta-lactam-beta-lactamase inhibitor combinations have a place in the
      treatment of multidrug-resistant pulmonary tuberculosis?

PMID- 7718856
TI  - Mycobacterium africanum osteoarthritis masked by Pseudomonas aeruginosa.

PMID- 7718857
TI  - High density cultivation of a recombinant CD-1 cell line producing prourokinase
      using a Biosilon microcarrier culture system.
AB  - CD-1, a genetically-engineered CHO cell line, was cultivated with a Biosilon
      microcarrier culture system. We successfully cultivated CD-1 cells to a very high
      density (over 1 x 10(7) cells/ml). Prourokinase was stably secreted at about 180
      IU/10(6) cells/24 h. Experiments showed that CD-1 cells growing on Biosilon
      microcarriers were able to spontaneously release from the microcarriers, then
      reattach and proliferate on fresh microcarriers. This makes it very easy to scale
      up production. The microcarriers could be reused several times without affecting
      adhesion, proliferation and prourokinase secretion. With CM-PECC membrane radial
      flow chromatography and MPG chromatography, the prourokinase in conditioned
      medium could be purified to a specific activity of 1 x 10(5) IU/mg of protein.
      The purification factor was about 600 fold, and approximately 90% of the
      biological activity was recovered.

PMID- 7718858
TI  - Identification of pathogenic leptospires by recombinant DNA probes.
AB  - Early diagnosis of leptospirosis of pulmonary diffuse hemorrhage type (PDH) is of
      crucial importance in saving patients. To develop a sensitive and specific method
      for diagnosis, a genomic library of the main pathogen of PDH, L. interrogans
      serovar lai strain 017, was constructed with the plasmid vector pUC9. Recombinant
      plasmids which have homologous fragments of pathogenic leptospires were screened
      from the bank. A recombinant plasmid, designated pCX7, could detect 1.7 kb
      fragment of strain 017, 9.0 kb of strain 601 and 30.0 kb of strain Hebdomadis,
      respectively, without cross hybridization with nonpathogenic leptospires such as
      L. biflexa strain Patoc I and Leptonema illini. The recombinant plasmid pCX7
      could detect pathogenic leptospires which are the main pathogens endemic to
      Sichuan Province.

PMID- 7718859
TI  - The autocrine regulatory effect of vasoactive intestinal peptide on the growth of
      human pancreatic carcinoma cells.
AB  - In the present study, the effects of VIP on the growth of two human pancreatic
      carcinoma cell lines PU-PAN-1 and PANC-1 were determined using tritiated
      thymidine incorporation. VIP receptors, intracellular cAMP and polyamines were
      investigated. The results indicated that VIP at a concentration of 10(-8) mol/L
      to 10(-7) mol/L can significantly stimulate the growth of PU-PAN-1 cells but not
      PANC-1 cells. This effect is dose-dependent and abolished by VIP receptor
      antagonist, [4-C1-Phe6, Leu17] VIP, suggesting VIP receptors in PU-PAN-1 cells
      may mediate this effect. VIP can markedly elevate the levels of intracellular
      cAMP and polyamines in PU-PAN-1 cells, indicating that the growth-promoting
      effect stimulated by VIP may be via a rapid increase in the biosyntheses of cAMP
      and polyamines. In addition, the VIP-antibody inhibited the growth of PU-PAN-1
      cells in serum-free culture medium. The results above suggested that VIP has an
      autocrine regulatory effect on this pancreatic carcinoma cell line (PU-PAN-1).

PMID- 7718860
TI  - Integration of traditional and modern methods in the identification of AFB
      cultures isolated from clinical specimens of patients with skin diseases.
AB  - This article reports the identification of 57 AFB cultures isolated from clinical
      specimens by using traditional methods (TM, including biochemical and cultural
      methods) and modern ELISA with monoclonal antibody (McAb-ELISA) and nested primer
      gene amplification assay (NPGAA). The representive AFB culture M. A1, A7, A19,
      A21 and A22) isolated from human lepromas were identified as new species by TM
      and it was shown that they were not identical to M. leprae by McAb-ELISA and
      NPGAA. Among another set of samples (M. S17, S1, S2, S2R, S7, S29), M. S17 was
      identical to M. scrofulaceum as assessed by TM only, while the others were found
      to be similar to M. tuberculosis and different from M. leprae using TM and McAb
      ELISA, and identical to M. tuberculosis with NPGAA. The authors conclude that TM
      and MM are very useful for identifying mycobacteria, while MM was much more
      sensitive and specific than TM. The selection and use of these methods depends on
      practical need.

PMID- 7718861
TI  - Changes of monoamines, purines and amino acids in rat striatum as measured by
      intercerebral microdialysis during ischemia/reperfusion.
AB  - The aim of this study was to determine the time course of changes in
      extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and
      their metabolites in the striatum of rats during ischemia and reperfusion, using
      intracerebral microdialysis as the sampling technique. In rats subjected to 20
      min forebrain ischemia by four-vessel occlusion, the concentrations of adenosine
      (Ade), inosine (Ino) and hypoxanthine (Hyp) were found to rise markedly. These
      changes were accompanied by dramatically elevated levels of aspartate (Asp),
      glutamate (Glu), taurine (Tau), gamma-aminobutyric acid (GABA), dopamine (DA) and
      norepinephrine (NE), all of which gradually returned to baseline following
      reperfusion. Concomitantly, the levels of metabolite 3,4-dihydroxyphenylacetic
      acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA) and
      xanthine (Xan) decreased during ischemia and gradually recovered 60-90 min after
      reperfusion. It was concluded that during global brain ischemia, the ECF is
      flooded with both potentially harmful (e.g. Asp, Glu, DA) and protective (e.g.
      Tau, GABA, Ade) agents.

PMID- 7718862
TI  - Study on the mechanism and effects of Gly-Tyr-NH2 and Gly-Tyr-Lys on rat luteal
      cells in vitro.
AB  - The action of Gly-Tyr-NH2, (GY-NH2) and Gly-Tyr-LYS(GYK) on 125I-LH binding, cAMP
      accumulation and progesterone production was investigated. Incubation of rat
      luteal cells for 2.5 h with GY-NH2 and GYK at dosage of 0.2 mmol/L caused a
      significant inhibition of basal and gonadotropin-stimulated steroidogenesis. GY
      NH2 and GYK were also found to reduce cAMP formation in response to hCG. The
      activity of adenylate cyclase of luteal cells was inhibited by 0.2 mmol/LGY-NH2
      and GYK. GY-NH2 and GYK at a concentration of 0.2 mmol/L were not found to have
      an inhibitory effect on 8Br-cAMP-stimulated progesterone production. GY-NH2 and
      GYK did not affect 125I-LH binding to LH receptors on the luteal cell surface.
      These results suggest that GY-NH2 and GYK inhibit steroidogenesis at the step of
      gonadotropin-stimulated cAMP formation in luteal cells. Adenylate cyclase in
      luteal cells was also inhibited.

PMID- 7718863
TI  - Oral transmucosal back permeation of alfentanil in dogs--a novel method to
      determine blood alfentanil concentration.
AB  - This study explores a novel noninvasive method for monitoring blood alfentanil
      concentrations using a dog model. Alfentanil which "back" permeated across the
      oral mucosa from the systemic circulation was collected from the oral mucosal
      surface and quantitated. The levels of the "back" permeated alfentanil were found
      to closely reflect real time serum alfentanil concentrations. With further work,
      this finding may lead to a novel noninvasive method for monitoring real time
      serum alfentanil concentrations in its clinical applications.

PMID- 7718864
TI  - A simplified in vivo dosimetry for total body irradiation prior to bone marrow
      transplantation.
AB  - For TBI (total body irradiation) prior to BMT (bone marrow transplantation) and
      in order to guarantee exact treatment, it is necessary to perfect in vivo
      dosimetry to detect any deviation of the treatment and to verify the dose
      distribution. A simplified and convenient transmission type in vivo dosimetry and
      problems are introduced and discussed.

PMID- 7718865
TI  - Effects of beta-endorphin on phytohemagglutinin-induced lymphocyte proliferation
      and mouse plaque-forming cell response via an opioid receptor mechanism.
AB  - The effects of opioid peptides on immune responses were investigated. It was
      found that beta-endorphin (beta-END) can depress proliferative responses to PHA
      in rat splenocytes but enhance those in mice, and it could also inhibit the
      plaque-forming cell (PFC) response to sheep red blood cells when mouse
      splenocytes immunized in vivo were cultured in vitro with the peptide. The
      peptide antagonist naloxone was able to reverse beta-END suppression of the PFC
      response. The data indicate that beta-END suppresses antibody production or
      secretion via a specific opioid-receptor-mediated mechanism.

PMID- 7718866
TI  - Evaluation of the antitumor activity of human IL-4 by in vitro and in vivo
      assays.
AB  - The characteristics of rhuIL-4 induced cytotoxicity was detected in vitro by
      using 51Cr release assay and the anti-tumor activity of rhuIL-4 induced killer
      cell was evaluated in vivo by using a human tumor model in nude mice. huIL-4 can
      induce LAK activity from peripheral blood lymphocytes (PBMC) stimulated with
      phytohemagglutinin (PHA). Compared with the LAK activity induced by rhuIL-2, the
      cytotoxicity of the killer cells induced by rhuIL-4 to K562 and Raji cells was
      lower, but that to TBL-E, a human lymphoid leukemia cell line established in our
      laboratory, and PHA-activated blast cells (PHA-blasts) was of similar magnitude.
      In the cytotoxicity assay using PHA-blasts, the addition of PHA increased the IL
      4-induced killer cell cytotoxicity by 131%, but had no effect on IL-2-induced
      killer cell cytotoxicity. This implies that IL-4 mainly induces CTL-like
      activity, while IL-2 mainly induces NK-like activity. An experimental human tumor
      model in nude mice was established by injection of TBL-E human leukemia cells.
      The anti-tumor activity of rhuIL-4 was evaluated by injection of human LAK cells
      induced from PHA-blasts by rhuIL-2+rhuIL-4 and human cytokines into tumor-bearing
      nude mice. The results showed that human LAK cells effectively inhibit the
      tumorigenicity of TBL-E cells in nude mice with an inhibition rate of 61%. The
      antitumor effect of rhuIL-2 was better than that of rIL-4, and the antitumor
      effect of rhuIL-2+rhuIL-4 was similar to that of rhuIL-2, though the former
      delayed the occurrence of tumors. Our data imply the potential application of
      human IL-4 in clinic, and provide an animal model to evaluate the anti-tumor
      activity of human cytokine(s) with species specificity.

PMID- 7718867
TI  - Patella and patellofemoral resurfacing (37 cases report).
AB  - Chondromalacia and patellofemoral osteoarthritis are common diseases that cause
      pain and disablement of the knee. Conservative therapy is not always effective.
      Since 1983 we have used isolated polyethylene patellar prosthesis for patella
      resurfacing of 19 patients with patellofemoral osteoarthritis. After an average
      of 44.9 months follow-up, we found the treatment was not as satisfactory as
      earlier trials. The main reason is the wide erosion of femoral condyle caused by
      the polyethylene patella. To overcome this shortness, we designed a new type of
      patellofemoral prosthesis which is named Y-L-Q. From January, 1991 to November,
      1993, we used this prosthesis to treat 16 knees of 13 patients with
      patellofemoral osteoarthritis. Most of those patients improved both
      symptomatically and functionally. The good to excellent results rate was 87.5%
      (14/16 knees) at the time of an average 16 months follow-up. The early results of
      our experience with patellofemoral resurfacing are encouraging, and extended
      follow-ups are in progress.

PMID- 7718868
TI  - Operations on aneurysms of the anterior communicating artery not visualized by
      cerebral angiography--report of four cases.
AB  - Four cases of anterior communicating aneurysms are reported with clinical
      presentations of recurrent intracranial hemorrhage undisclosed in their cerebral
      angiography. Operative exploration revealed anterior communicating aneurysms in
      these patients. It is thought possible that these patients harbored aneurysms
      which failed to exhibit on angiograms due to temporary thrombosis or development
      of abnormal cerebral vessels. CT scanning was important for diagnosis of these
      patients.

PMID- 7718869
TI  - A clinical analysis of 38 patients with primary tracheo bronchial tumors.
AB  - During a 17-year period, 38 patients with primary tracheobronchial tumors
      received surgical treatment in PUMC Hospital. Among the 38, 12 had low-malignancy
      tracheal tumors, 11 had benign tracheal tumors, 14 had low malignancy bronchial
      tumors and 1 had a benign bronchial tumor. Fifteen operations were performed on
      12 patients with low-malignancy tracheal tumors, including local resection of the
      tumor and tracheal wall in 4 and curettage of the tumor plus electrical
      cauterization in 10. Postoperative radiotherapy was used as an adjuvant treatment
      in 8 patients with adenocystic carcinoma. Eight patients have survived for more
      than 5 years and 3 patients have survived for longer than 10 years
      postoperatively. All 11 patients with benign tumors received curettage of the
      tumor and were followed up for an average of 6.5 years. Among them, 9 are still
      alive. Of the 14 patients with low malignancy bronchial tumors, 5 underwent
      curettage of the tumor plus electrical cauterization through incision of the main
      bronchus or intermedial bronchus, and 7 underwent lobectomy or pneumonectomy. The
      authors conclude that the correct diagnosis rate can be increased by enhancing
      recognition of this disease and applying tracheal tomography and bronchoscopy.

PMID- 7718870
TI  - Childhood monosomy 7: epidemiology, biology, and mechanistic implications.

PMID- 7718871
TI  - Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue.
AB  - Characteristic chromosomal aberrations have been associated with subtypes of non
      Hodgkin's lymphoma with distinct clinicopathologic features. Low-grade B-cell
      lymphomas of mucosa-associated lymphoid tissue (MALT) form such a group and might
      be expected to be characterized by a specific cytogenetic abnormality. Metaphase
      analyses of MALT lymphoma are rare due to problems with fresh tissue collection
      and poor in vitro proliferation. However, the small number of published series
      suggests that chromosome trisomies, particularly trisomy 3, might be
      characteristic of these tumors. The application of interphase cytogenetic
      techniques to routinely processed material allows the examination of a large
      series of archival cases and is particularly useful for the demonstration of
      chromosome trisomies. We have used this technique to analyze 70 cases of low
      grade MALT lymphoma from various sites and found trisomy 3 in 60%. This finding
      compares with 16% in low-grade nodal B-cell lymphoma and 27% in primary splenic
      lymphoma of marginal zone type (splenic lymphoma with villous lymphocytes). These
      results provide further evidence that low-grade MALT lymphomas from all sites
      form a single pathologic entity distinct from nodal B-cell lymphomas. Although
      MALT lymphoma and primary splenic lymphoma may arise from marginal zone B cells,
      they are genetically distinct.

PMID- 7718872
TI  - Characterization of CD33 as a new member of the sialoadhesin family of cellular
      interaction molecules.
AB  - CD33 is a member of the Ig superfamily that is restricted to cells of the
      myelomonocytic lineage but whose functions and binding properties are unknown. It
      shares sequence similarity with sialoadhesin, CD22, and the myelin-associated
      glycoprotein, which constitute the Sialoadhesin family of sialic acid-dependent
      cell adhesion molecules. In the present study, we show that CD33 is a fourth
      member of this family. As a model for sialic acid-dependent binding, human
      erythrocytes were derivatized with N-acetylneuraminic acid (NeuAc) in different
      linkages. A recombinant soluble form of CD33, Fc-CD33, bound red blood cells with
      a specificity similar to that of sialoadhesin, preferring NeuAc alpha 2,3Gal in N
      and O-glycans over NeuAc alpha 2,6Gal in N-glycans. Fc-CD33 also bound
      selectively to the myeloid cell lines HL-60 and U937. However, CD33 was unable to
      mediate cell binding after transient expression in COS cells, despite high levels
      of surface expression. Pretreatment of the CD33-transfected cells with sialidase
      rendered them capable of mediating sialic acid-dependent binding. These results
      show that CD33 can function as a sialic acid-dependent cell adhesion molecule and
      that binding can be modulated by endogenous sialoglycoconjugates when CD33 is
      expressed in a plasma membrane.

PMID- 7718873
TI  - Homozygous deletions of the p16 tumor-suppressor gene are associated with
      lymphoid transformation of chronic myeloid leukemia.
AB  - The p16 gene, also referred to as MTS1, INK4, CDK4I, or CDKN2, at chromosome 9p21
      has recently been described as a tumor suppressor that may be involved in a wide
      range of tumors. We have used a semiquantitative multiplex polymerase chain
      reaction assay to search for deletions of the p16 gene in 34 patients with
      chronic myeloid leukemia in blast crisis (CML BC), 19 patients with acute
      lymphoblastic leukemia (ALL), and 25 patients with acute myeloid leukemia (AML).
      Homozygous deletions of p16 exons were found in 5 of 10 (50%) patients with CML
      in lymphoid BC and in 5 (26%) ALL patients, but in only 1 (2%) case with AML. No
      deletions were found in CML BC of nonlymphoid phenotype. Comparison of chronic
      phase DNA or remission DNA with acute leukemia DNA in 5 individuals showed that
      the p16 deletions were acquired and not inherited, directly implicating these
      lesions in the pathogenesis of the disease. We conclude that functional
      elimination of the p16 gene, or a closely mapping gene, is involved in a
      significant number of patients with CML in lymphoid transformation.

PMID- 7718874
TI  - Cloning of several species of MLL/MEN chimeric cDNAs in myeloid leukemia with
      t(11;19)(q23;p13.1) translocation.
AB  - The t(11;19)(q23;p13.1) translocation is thought to play an important role in
      pathogenesis of myeloid leukemias in older patients. The MLL gene involved in
      other 11q23 abnormalities was also rearranged by this translocation. Screening of
      cDNA libraries of the t(11;19)(q23;p13.1)-carrying leukemic cells resulted in the
      isolation of several species of fusion cDNAs between the MLL gene and an unknown
      gene on 19p13.1, named MEN (myeloid eleven-nineteen translocation), which is
      ubiquitously expressed. Although the MLL gene was alternatively spliced, the
      fusion protein should contain an N-terminal half of the MLL, including AT hook
      motifs, that is fused to the MEN protein with a lysine-rich sequence, suggesting
      that the MLL/MEN fusion protein could be a chimeric transcription factor. The
      MLL/MEN fusion transcripts of 8.0 kb were detected in leukemic cells of two cases
      with the translocation. The MLL/MEN fusion was consistent in all three cases of
      the t(11;19)(q23;p13.1)-carrying leukemia examined by RNA-based polymerase chain
      reaction. These findings strongly suggest that the t(11;19)(q23;p13.1) results in
      the fusion formation encoding a new class of potential chimeric transcription
      factor that contributes to leukemogenesis of myeloid lineage.

PMID- 7718875
TI  - A five-drug remission induction regimen with intensive consolidation for adults
      with acute lymphoblastic leukemia: cancer and leukemia group B study 8811.
AB  - The goal of this phase II multicenter clinical trial was to evaluate a new
      intensive chemotherapy program for adults with untreated acute lymphoblastic
      leukemia (ALL) and to examine prospectively the impact of clinical and biologic
      characteristics on the outcome. One hundred ninety-seven eligible and evaluable
      patients (16 to 80 years of age; median, 32 years of age) received
      cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase; 167
      patients (85%) achieved a complete remission (CR), 13 (7%) had refractory
      disease, and 17 (9%) died during induction. A higher CR rate was observed in
      younger patients (94% for those < 30 years old, 85% for those 30 to 59 years old,
      and 39% for those > or = 60 years old, P < .001) and in those who had a
      mediastinal mass (100%) or blasts with a T-cell immunophenotype. Eighty percent
      of B-lineage and 97% of T-cell ALL patients achieved a CR (P = .01). The
      coexpression of myeloid antigens did not affect the response rate or duration.
      Seventy percent of those with cytogenetic or molecular evidence of the
      Philadelphia (Ph) chromosome and 84% of those without such evidence achieved a CR
      (P = .11). Patients in remission received multiagent consolidation treatment,
      central nervous system prophylaxis, late intensification, and maintenance
      chemotherapy for a total of 24 months. After a median follow-up time of 43
      months, the median survival for all 197 patients is 36 months; the median
      remission duration for the 167 CR patients is 29 months. Favorable pretreatment
      characteristics relative to remission duration or survival are younger age, the
      presence of a mediastinal mass or lymphadenopathy, a white blood cell count (WBC)
      less than 30,000/microL, L1 morphology, T or TMy immunophenotype, and the absence
      of the Ph chromosome. The estimates of the proportion surviving at 3 years are
      69% for patients less than 30 years old, 39% for those 30 to 59 years old, 89%
      for those who had a mediastinal mass, 59% with WBC less than 30,000/microL, 63%
      with L1 morphology, 69% for T or TMy antigen expression, and 62% for those who
      lack the Ph chromosome. Fifteen patients (8%) had no unfavorable prognostic
      factors and have an estimated probability of survival at 5 years of 100% (95%
      confidence interval, 77% to 100%). This intensive chemotherapy regimen produces a
      high remission rate and a high proportion of durable remissions in adults with
      ALL.

PMID- 7718876
TI  - Constitutive in vivo cytokine and hematopoietic growth factor gene expression in
      the bone marrow and peripheral blood of healthy individuals.
AB  - We investigated hematopoietic growth factor (HGF) and cytokine gene expression in
      the bone marrow (BM) and peripheral blood (PB) of healthy individuals as a
      starting point for delineating the physiologic role of cytokines in steady state
      hematopoiesis. BM biopsy specimens and PB samples from 7 healthy individuals were
      analyzed by polymerase chain reaction amplification of reverse-transcribed RNA
      using gene-specific primer sets. Consistent gene expression in the BM of all 7
      individuals was detected for macrophage colony-stimulating factor (CSF), stem
      cell factor, interleukin-6 (IL-6), IL-7, erythroid-potentiating factor, erythroid
      differentiating factor, and insulinlike growth factor 1, all cytokines with
      reported direct stimulatory effects on in vitro hematopoiesis. Of these,
      erythroid-potentiating factor and erythroid-differentiating factor appeared to be
      the only stimulating factors that were also expressed in the PB. Among the
      cytokines with inhibitory effects on in vitro hematopoiesis IL-4, tumor necrosis
      factor-alpha (TNF-alpha), TNF-beta, transforming growth factor-beta, and
      macrophage inflammatory protein-1 alpha were expressed in the BM of the 7
      individuals. Except for TNF-alpha, the latter cytokines were also expressed in
      the PB. Consistent expression in the BM and PB of all tested individuals was also
      observed for IL-1 beta, IL-1 receptor antagonist, and IL-1 beta converting
      enzyme, which are all members of the IL-1 family with a possible indirect effect
      on hematopoiesis. Remarkably, no expression of granulocyte CSF, granulocyte
      macrophage CSF, and IL-3 was found in the BM or PB of all investigated
      individuals (n = 15). This was also the case for IL-1 alpha, IL-2, IL-5, IL-9, IL
      12, IL-13, leukemia-inhibiting factor, interferon-gamma, and inhibin. Weak IL-8
      and IL-10 expression was found in the BM and/or PB of a minority of investigated
      individuals. These findings provide insight into which cytokines or HGFs
      potentially are involved in the autocrine or paracrine regulation of in vivo
      steady state hematopoiesis. The absence of expression of granulocyte CSF,
      granulocyte-macrophage CSF, and IL-3 in the BM of healthy individuals implicates
      that it is highly unlikely that these HGFs are involved in the autocrine or
      paracrine regulation of constitutive hematopoiesis.

PMID- 7718877
TI  - Localization of the inducible enhancer in the mouse interleukin-5 gene that is
      responsive to T-cell receptor stimulation.
AB  - Transcriptional regulation of the interleukin-5 (IL-5) gene in T lymphocytes
      appears to be of central importance in the control of the eosinophilia
      characteristic of allergic responses and certain parasite infections. Previous
      studies of IL-5 gene regulation have been hampered by the lack of a transfection
      assay, which detects the antigen-responsive enhancer in the IL-5 promoter. Here
      we show that stable transfection of the Th2 clone D10.G4.1 and the T lymphoma
      EL4.23 with chloramphenicol acetyltransferase reporter gene constructs carrying
      the region to -3859 gives inducible expression with the known regulatory
      characteristics of the endogenous IL-5 gene. To facilitate detailed analysis of
      the promoter region, 3.9 kb of DNA sequence immediately up stream of the start of
      transcription was determined and the minimum upstream region required for
      inducible expression was further localized, by stable transfection studies in
      EL4.23 cells, to the region up to -1016. A CTF/NF1 site in the upstream enhancer
      at -940 to -928 was shown to be required for regulated inducible expression.
      Mutation of this sequence motif abolished inducibility and also prevented binding
      of the sequence to a nuclear protein(s). A TCATTT-containing element in the
      proximal promoter region was also demonstrated to be essential for inducible
      expression of the IL-5 gene, similar to the role of this conserved element in the
      transcriptional regulation of the granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and IL-4 genes.

PMID- 7718878
TI  - The Apple 1 and Apple 4 domains of factor XI act synergistically to promote the
      surface-mediated activation of factor XI by factor XIIa.
AB  - Binding sites for high molecular weight kininogen (HK) and for factor XIIa are
      present in the Apple 1 (A1) and the A4 domains of factor XI, respectively. To
      define the roles of these two sites in surface-mediated factor-XI activation we
      prepared conformationally constrained synthetic peptides and recombinant A1
      domain (rA1) and determined their effects on the activation of factor XI by
      factor XIIa in the presence of HK and either kaolin or dextran sulfate. Surface
      mediated factor-XI activation by factor XIIa was inhibited by a conformationally
      constrained A4 peptide (Ala317-Gly350), by an A1 peptide (Phe56-Ser86), and by
      rA1 (Glu1-Ser90). When used in combination at equimolar concentrations, rA1 and
      A4 peptide were 10-fold more effective than either one alone in inhibiting
      surface-mediated activation of factor XI by factor XIIa. The A4 peptide was a
      competitive inhibitor of factor XIIa amidolytic activity and a noncompetitive
      inhibitor of factor-XI activation by factor XIIa, whereas rA1 and the A1 peptide
      did not inhibit factor XIIa. The rA1 domain inhibited factor XI binding to HK,
      whereas the A4 peptide did not. We conclude that specific sequences exposed on
      the surfaces of the A1 (Val59-Lys83) and A4 (Ala317-Gly350) domains of factor XI
      act synergistically to promote surface-mediated factor-XI activation by factor
      XIIa in the presence of HK by binding factor XI to surface-bound HK (A1 domain)
      and by binding factor XIIa near the cleavage site (Arg369-Ile370) of factor XI
      (A4 domain).

PMID- 7718879
TI  - Expression of HOXC4 homeoprotein in the nucleus of activated human lymphocytes.
AB  - We have analyzed the expression of homeoproteins of the HOX family in resting and
      activated lymphoid cells and in neoplastic lymphoid cell lines by the use of
      monoclonal antibodies (MoAbs) already shown to react with the homeoproteins
      HOXA10, HOXC6, and HOXD4, respectively. Anti-HOXA10 and C6 MoAbs DIDi not show
      any reactivity with the lymphoid cells tested, whereas anti-HOXD4 MoAb stained
      few resting peripheral blood lymphocytes (PBLs) and most phytohemagglutinin (PHA)
      stimulated PBLs as early as 6 hours after stimulation. The pattern of staining of
      PHA-activated PBLs is reminiscent of the stages of nucleolar fragmentation in
      different phases of the cell cycle. The MoAb reacted also with activated or
      Epstein-Barr virus-transformed B cells, with clonal or polyclonal T and natural
      killer (NK) cells, with leukemic T-cell lines, and with a Burkitt's lymphoma cell
      line. RNAse protection experiments, per formed with probes specific for HOXD4 or
      for the highly homologous HOXA4, HOXB4, and HOXC4, belonging to the same paralogy
      group, indicated that only HOXC4 mRNA is present in resting or activated PBLs.
      Northern blot analysis on polyA+ RNA from activated PBLs or Raji cells showed the
      presence of two different HOXC4 transcripts of 2.8 and 1.9 kb. Gel retardation
      and Southwestern blot assays showed the presence of a 32-kD homeoprotein with DNA
      binding properties typical of a HOX4 homeoprotein in nucleolar extracts of PHA
      activated, but not of resting, lymphocytes. Taken together, these data indicate
      that the HOXC4 homeoprotein is expressed in activated and/or proliferating
      lymphocytes of the T-, B-, or NK-cell lineage, whereas it is weakly expressed in
      a minority of resting cells. The early expression and the nucleolar localization
      suggest an involvement of HOXC4 in the regulation of genes controlling lymphocyte
      activation and/or proliferation.

PMID- 7718880
TI  - Blood transfusions and immunophenotypic alterations of lymphocyte subsets in
      sickle cell anemia. The Transfusion Safety Study Group.
AB  - Transfusions purportedly induce dysfunction of cell-mediated immunity in sickle
      cell anemia (SCA). We studied hematologic and lymphocytic indices in 173 human
      immunodeficiency virus (HIV)-negative subjects with SCA and 131 black controls.
      Children aged 1 to 7 years with SCA had leukocyte counts and percentages of
      granulocytes, monocytes, natural killer cells, and T-cell markers (CD2+CD11b+,
      CD4+CD26+, CD4+CD29+) that were significantly higher than those for control
      children. Percent total lymphocytes was decreased for this age group, but the
      total number of lymphocytes and T and B cell counts were similar to controls.
      Platelets were not increased. Adolescents (aged 8 to 17 years) and adults (aged >
      or = 18 years) with SCA had increased total leukocytes and monocytes and
      lymphocytes counts that remained level instead of decreasing, as did comparably
      aged controls. Lymphocyte subsets typically increased in count, but their
      percentage remained similar to children. The exception was CD56+ cell counts,
      which were increased in adolescents and adults. No lymphocytic subset change
      suggested impaired cellular immunity, and none could be related to transfusion.
      Prophylactically transfused patients had higher granulocyte counts, but these may
      arise from the complications of SCA itself.

PMID- 7718881
TI  - Engrafted maternal T cells in a severe combined immunodeficiency patient express
      T-cell receptor variable beta segments characterized by a restricted V-D-J
      junctional diversity.
AB  - To better understand the peculiar functional behavior of engrafted maternal T
      cells in a severe combined immunodeficiency (SCID) patient, we characterized, at
      the molecular level, the T-cell repertoire of a SCID child with a high number of
      engrafted, mature, activated lymphocytes. We found that, although these
      transplacentally acquired T cells express a random set of T-cell receptor
      variable beta (TCRBV) segments, the TCRBV transcripts are characterized by an
      extremely restricted V-D-J junctional diversity. Only a few cDNA clones were
      dominant among the TCRBV4+, TCRBV6+, and TCRBV20+ populations in engrafted cells,
      whereas the same TCRBV chains expressed by the mother's lymphocytes had the
      expected junctional hetero-geneity. Highly diverse and polyclonal junctions were
      also expressed by maternal cells activated in mixed lymphocyte reaction by
      Epstein-Barr virus (EBV)-transformed B lymphocytes from the patient, indicating
      that the strong clonal selection that characterizes the engrafted cells
      repertoire is probably not due to allorecognition. Furthermore, we report that
      the repertoire of the transplacentally acquired lymphocytes is dynamic over time
      and is characterized by waves of expression and contraction of selected clones,
      expressing different TCRBV segments. These results help to explain some of the
      abnormal functional behaviors of engrafted maternal cells and raise new questions
      regarding the mechanisms responsible for the restricted clonal diversity.

PMID- 7718882
TI  - Effects of the Th1 and Th2 stimulatory cytokines interleukin-12 and interleukin-4
      on human immunodeficiency virus replication.
AB  - The cytokines interleukin-12 (IL-12) and IL-4 play important roles in the
      development of Th1-like (type-1) and Th2-like (type-2) T-cell responses,
      respectively, and there is evidence that type-1/type-2 T helper imbalances are
      important in the pathogenesis of human immunodeficiency virus (HIV) disease. With
      this background, we examined the effects of these cytokines on HIV replication.
      Neither stimulated HIV replication in fresh peripheral blood mononuclear cells
      (PBMC). However, in prestimulated PBMC, IL-12, and to a greater extent, IL-4 as
      well as IL-2, induced production of HIV p24 antigen over 7 days of culture (no
      cytokine 3,900 x/divided by 1.31 [GM x/divided by SEM] pg/mL; IL-12, 34,300
      x/divided by 1.39 pg/mL; IL-4, 283,000 x/divided by 1.14 pg/mL; and IL-2, 328,000
      x/divided by 1.31 pg/mL). Neither IL-12- nor IL-4-induced HIV replication was
      attributable to induction of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, or
      TNF-beta. Both IL-12- and IL-4-induced HIV replication was associated with
      selective loss of the CD4+ subset in stimulated cultures. IL-4 stimulated HIV
      replication in monocyte/macrophages, while IL-12 had little or no effect in these
      cells. Finally, HIV replication stimulated by IL-12 or IL-4 was inhibited by
      dideoxynucleosides. Thus, IL-12 and IL-4 enhance HIV replication and HIV-induced
      cell death in prestimulated PBMC. Through killing of the CD4+ T cells stimulated
      by these cytokines, this may result in inappropriate type-1/type-2 responses in
      HIV-infected patients and contribute to their Th1 immunodeficiency.

PMID- 7718883
TI  - Differential effects of ifosfamide on the capacity of cytotoxic T lymphocytes and
      natural killer cells to lyse their target cells correlate with intracellular
      glutathione levels.
AB  - We established an in vitro model to study the influence of ifosfamide treatment
      on intracellular glutathione (GSH) levels in activated human effector cells with
      specific phenotypes and immunologic functions. Besides its role as the major
      intracellular reductant, GSH has been shown to affect the initiation and
      progression of lymphocyte activation after stimulation with lectins. An
      incubation of activated human peripheral blood lymphocytes (PBL) with 4
      hydroxyifosfamide, the activated form of ifosfamide (4-OH-IF), resulted in a
      depletion of the intracellular GSH levels and a significant inhibition of the
      proliferative capacity in a dose-dependent manner. The cytotoxic activity of
      separated CD3- natural killer (NK) cells and CD3+ allospecific, cytotoxic T
      lymphocytes (CTL), either untreated or treated with 4-OH-IF at different
      concentrations, was compared in a standard 51chromium release assay (CML). There
      were three major findings. (1) The capacity of CD3+ major histocompatibility
      complex (MHC)-restricted CTL to lyse their specific allogeneic target cells was
      substantially reduced by preincubation of the effector cells with 4-OH-IF. This
      inhibition of the lytic activity in CD3+ CTL correlated with a substantial
      depletion of the intracellular GSH levels in this population. Rapid
      reconstitution of depleted GSH levels and restoration of cytotoxic activity of
      CTL was achieved by incubation of the effector cells with thiols, eg, glutathione
      ester (GSH-ester) or 2-mercaptoethanesulfonate (mesna). (2) In contrast, the
      lytic activity in CD3- NK cells was not substantially affected (up to 100 mumol/L
      4-OH-IF). This result correlates with the capacity of NK cells to maintain their
      intracellular GSH levels after an ifosfamide treatment. (3) In comparison with
      CD3+ CTL, CD3- NK cells are more resistant to an ifosfamide treatment because
      they have higher initial GSH levels and a more than fourfold higher relative rate
      of GSH synthesis.

PMID- 7718884
TI  - Detection of myc translocations in lymphoma cells by fluorescence in situ
      hybridization with yeast artificial chromosomes.
AB  - Translocations involving chromosome 8 at band q24 and one of the Ig loci on
      chromosomes 14q32, 22q11, and 2p11 are the hallmark of Burkitt's lymphoma (BL).
      It has been previously observed that the exact localization of the breakpoints at
      chromosome 8q24 can vary significantly from patient to patient, scattering over a
      distance of more than 300 kb upstream of c-myc and about 300 kb downstream of c
      myc. To generate probes for fluorescence in situ hybridization (FISH) that detect
      most c-myc translocations, we screened a yeast artificial chromosome (YAC)
      library from normal human lymphocytes by colony hybridization, using three
      markers surrounding the c-myc gene as probes. We obtained 10 YAC clones ranging
      in size between 500 and 200 kb. Two nonchimeric clones were used for FISH on
      several BL cell lines and patient samples with different breakpoints at 8q24. Our
      results show that the YAC clones detected translocations scattered along
      approximately 200 kb in both metaphase chromosomes and interphase nuclei. The
      sensitivity, rapidity, and feasibility in nondividing cells render FISH an
      important diagnostic tool. Furthermore, the use of large DNA fragments such as
      YACs greatly simplifies the detection of translocations with widely scattered
      breakpoints such as these seen in BL.

PMID- 7718885
TI  - Antitumor activity of anti-CD30 immunotoxin (Ber-H2/saporin) in vitro and in
      severe combined immunodeficiency disease mice xenografted with human CD30+
      anaplastic large-cell lymphoma.
AB  - To develop a novel adjunctive therapy for CD30 (Ki-1)+ anaplastic large-cell
      lymphoma (ALCL), we investigated in preclinical studies the antitumor activity of
      an immunotoxin (IT) constructed by coupling the plant ribosome-inactivating
      protein saporin (SO6) to the monoclonal antibody (MoAb) Ber-H2 that is directed
      against the CD30 molecule, a new member of the tumor necrosis factor receptor
      (TNFR) super-family. The activity of Ber-H2/SO6 IT was tested both in vitro
      against the CD30+ ALCL-derived cell line JB6 and in vivo using our severe
      combined immunodeficiency disease (SCID) mouse model of human xenografted CD30+
      ALCL. In vitro, the Ber-H2/SO6 IT was selectively and highly toxic to the JB6
      cell line [50% inhibiting concentration (IC50), 3.23 x 10(-12) mol/L as SO6]. In
      vivo, a 3-day treatment with nontoxic doses of Ber-H2/SO6 (50% of LD50) induced
      lasting complete remissions (CR) in 80% of mice when started 24 hours after tumor
      transplantation. In contrast, injection of the IT at later stages of tumor growth
      (mice bearing subcutaneous tumors of 40- to 60-mm3 volume), induced CR in only 6
      of 21 (approximately 30%) mice and significantly delayed tumor growth rate (P <
      .01). This finding suggests that maximum effect of the anti-CD30 IT is observed
      when tumor cell burden is small. Persistent tumors from IT-treated mice consisted
      of CD30+ cells, thus excluding the possibility that selection of CD30-negative
      mutant clones during IT therapy was responsible for resistance to treatment. We
      conclude that Ber-H2/SO6 IT is an effective agent against CD30+ ALCL growing in
      SCID mice, suggesting its possible role as adjuvant therapy in patients with
      CD30+ ALCL refractory to standard treatments.

PMID- 7718886
TI  - Multi-unit ribozyme-mediated cleavage of bcr-abl mRNA in myeloid leukemias.
AB  - Chronic myelogenous leukemia is characterized by the Philadelphia chromosome,
      which at the molecular level results from the fusion of the bcr gene on
      chromosome 22 and the abl gene on chromosome 9. The bcr-abl fusion gene encodes a
      novel tyrosine kinase with transforming activity. In this study, we have
      synthesized a multi-unti ribozyme that targets bcr-abl mRNA. In vitro ribozyme
      cleavage reactions show increased cleavage efficiency of this multi-unit ribozyme
      compared with single or double ribozymes. The multiunit ribozyme was then
      transfected into murine myeloblasts transformed with the bcr-abl gene (32D
      cells). Ribozyme transfection was accomplished either by liposomes or using
      follic acid-polylysine as a carrier. Multi-unit ribozyme transfection reduced the
      level of bcr-abl mRNA 3 logs when transfected via folate receptor-mediated uptake
      into transformed 32D cells. These results suggest that a multi-unit ribozyme
      could be an effective therapeutic agent for the treatment of Philadelphia
      chromosome-positive chronic myelogenous leukemia.

PMID- 7718887
TI  - BCR-ABL, ABL-BCR, BCR, and ABL genes are all expressed in individual granulocyte
      macrophage colony-forming unit colonies derived from blood of patients with
      chronic myeloid leukemia.
AB  - It has been suggested that the BCR-ABL gene of chronic myeloid leukemia (CML) is
      not uniformly expressed in Philadelphia (Ph)-positive cells, and that BCR-ABL
      gene expression precludes transcription of the normal BCR or ABL genes.
      Therefore, we have analyzed granulocyte-macrophage colony-forming unit (CFU-GM)
      colonies derived from peripheral blood of 11 CML patients by cytogenetic and by
      reverse transcriptase-polymerase chain reaction (PCR) amplification of BCR-ABL,
      ABL-BCR, BCR, and ABL. All CFU-GM colonies with analyzable metaphases were found
      to contain a Ph chromosome. In 2 patients, the initial PCR screening failed to
      detect BCR-ABL transcripts in 2 of 11 and 1 of 7 Ph-positive colonies. However,
      when amplification for BCR-ABL was repeated in quintuplicate, all but 1 colony
      from a single patient showed one or more positive results. Amplifications of the
      four genes in each colony showed that BCR-ABL, ABL-BCR, and the normal BCR and
      ABL were simultaneously expressed in the majority of CFU-GM colonies. Replicate
      PCR tests for BCR and for ABL in colonies initially scored as negative also
      uncovered previously undetected positive amplifications. We conclude that BCR-ABL
      expression does not suppress transcription from the normal BCR and ABL genes, and
      that Ph-positive, BCR-ABL-negative colonies derived from peripheral blood CFU-GM
      are rare or nonexistent.

PMID- 7718888
TI  - Analysis of VH genes used by neoplastic B cells in endemic Burkitt's lymphoma
      shows somatic hypermutation and intraclonal heterogeneity.
AB  - Tumor cell lines from six typical cases of endemic Epstein-Barr virus (EBV)
      genome-positive Burkitt's lymphoma (BL) have been investigated for usage and
      mutational pattern of Ig VH genes. The neoplastic cells all had a t(8;14)
      (q24;q32) translocation involving the c-myc protooncogene. The VH genes were
      derived from VH1, VH3 and VH4, and both the IgM-positive (four cases) and IgG
      positive (two cases) were extensively mutated from germline sequence. In two
      cases, early and late passage tumor cells were available, and the VH nucleotide
      sequences were identical, indicating that mutations had not accumulated in vitro.
      In a further case, there was evidence of sequence heterogeneity, which appeared
      to have been generated in vivo, indicating that the tumor cell VH gene was able
      to undergo posttranslocation somatic hypermutation. Analysis of the relatively
      nonpolymorphic VH4 genes for the pattern of replacement or silent mutations did
      not show a role for antigen selection in the expressed sequences.

PMID- 7718889
TI  - Interleukin-12 expression in human lymphomas and nonneoplastic lymphoid
      disorders.
AB  - Interleukin-12 (IL-12), a cytokine with in vitro and in vivo immunomodulatory
      effects, is produced by lymphocytes and stimulated monocytes. Little is known
      about the production and possible role of IL-12 in human lymphoproliferative
      disorders. We examined IL-12 expression by immunohistochemistry using antibodies
      recognizing the p40, p35 subunits, and the p70 heterodimeric IL-12 protein, and
      by Northern blot in lymph nodes from patients with Hodgkin's disease (HD), non
      Hodgkin's lymphomas (NHL), and nonneoplastic lymphoid lesions. In the majority of
      the HD cases (28 of 34), IL-12 immunoreaction was found in small lymphoid cells
      cultured around Hodgkin and Reed-Sternberg (H&RS) cells. No IL-12 signal was seen
      in H&RS cells. Transcripts for IL-12 were found by Northern and dot blot analysis
      in 13 of 19 (IL-12 p40) and 11 of 19 (IL-12 p35) cases. The HD cases were further
      examined for the presence of Epstein-Barr virus (EBV) latent membrane protein
      (LMP-1). All cases with EBV-LMP-1 positivity (22 of 34 cases) also expressed IL
      12. No IL-12 immunoreaction was found in neoplastic cells of 33 cases of various
      NHLs, which were all LMP-1 negative and showed no EBV-genome sequence, as
      assessed by polymerase chain reaction (PCR). In 24 nonneoplastic lymphoid
      lesions, few dispersed IL-12 positive cells were seen in the parafollicular area
      and in the sinus of the lymph node. The marked presence of IL-12 in the majority
      of HD cases indicates that IL-12 might play a role in the pathobiology of HD,
      suggesting that this cytokine is involved in EBV-positive HD.

PMID- 7718890
TI  - TP53 mutations emerge at early phase of myelodysplastic syndrome and are
      associated with complex chromosomal abnormalities.
AB  - We examined TP53 mutation in 57 patients with myelodysplastic syndrome (MDS) at
      either the MDS phase or at the terminal leukemic phase using polymerase chain
      reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis.
      TP53 mutations within exons 5 through 8 were found in seven patients. All these
      mutations were detected at the presentation of MDS whether these patients showed
      leukemic transformation or not. TP53 mutations were frequently found in patients
      with loss of the short arm of chromosome 17 (17p-) (three of seven patients with
      17p-, 43%) and complex karyotypic abnormalities (five of 14, 38%). Among the
      seven patients with the TP53 mutation, four patients progressed to acute leukemia
      within 7 months from the diagnosis of MDS, and the remaining three died within 7
      months without leukemic transformation. These findings suggest that mutations of
      the TP53 can be implicated in leukemic transformation and a poor prognosis in
      MDS.

PMID- 7718891
TI  - Intracellular pattern of cytosolic Ca2+ changes during adhesion and multiple
      phagocytosis in human neutrophils. Dynamics of intracellular Ca2+ stores.
AB  - The subcellular pattern of cytosolic free Ca2+ ([Ca2+]i) changes in human
      polymorphonuclear neutrophils (PMNs) was studied using imaging of fura-2
      fluorescence (time resolution 12.5 ratios/s) to determine whether PMNs could
      obtain directional information from the [Ca2+]i signal. [Ca2+]i changes were
      observed during initial adherence, the subsequent chemotactic movement, and the
      phagocytosis of opsonized yeast particles. Initial adherence was followed by a
      rapid increase in [Ca2+]i (from 90 +/- 10 to 290 +/- 40 nmol/L in 6.5 +/- 2.5
      seconds; +/- SEM, n = 10), apparently homogeneously distributed over the entire
      cytoplasm, which preceded the spreading of the PMNs. [Ca2+]i increases after the
      contact of the PMNs with yeast particles were of lower mean amplitude; [Ca2+]i
      increased simultaneously throughout the cytosol. In the absence of extracellular
      Ca2+, multiple phagocytotic events could proceed normally without a mandatory
      [Ca2+]i transient. In PMNs polarized on phagocytosis, gradients in [Ca2+]i could
      be observed. [Ca2+]i was more elevated in the periphagosomal area than in the
      remaining parts. Taken together, these data show that [Ca2+]i waves do not
      provide the neutrophil with directional information during chemotaxis and
      phagocytosis. Sustained small inhomogeneity of [Ca2+]i levels are consistent with
      a proposed redistribution of releasable Ca2+ stores on phagocytosis.

PMID- 7718892
TI  - Identification of signaling motifs within human Fc gamma RIIa and Fc gamma RIIb
      isoforms.
AB  - To assess the functional capacity of the heterogeneous Fc gamma RII (CD32) family
      and to identify critical regions for functioning, we generated a panel of B-cell
      transfectants. The Fc gamma R-negative B-cell line IIA1.6 was transfected with
      wild-type or mutant human Fc gamma RIIa and IIb molecules. Solely Fc gamma RIIa
      expressing IIA1.6 cells were capable of phagocytosing opsonized Staphylococcus
      aureus bacteria, and cross-linking of Fc gamma RIIa triggered a rapid induction
      of tyrosine phosphorylation after 20 seconds. Analysis of Fc gamma RIIa mutants
      identified the immunoreceptor tyrosine-based activation motif (ITAM; previously
      described as ARH-1 motif) within the IIa cytoplasmic tail to be critical for B
      cell activation. In contrast, Fc gamma RIIb isoforms triggered tyrosine
      phosphorylation on cross-linking with much slower kinetics (> 3 minutes) than Fc
      gamma RIIa. Furthermore, solely Fc gamma RIIb molecules proved capable of
      downregulating [Ca2+]i and interleukin-2 production on co-cross-linking with sIgG
      in IIA1.6. The Fc gamma RIIb-mediated functions were absent in Fc gamma RIIb
      mutants in which the tyrosine or leucine within the YSLL motif in a conserved 13
      aa region (now known as immunoreceptor tyrosine-based inhibitor motif [ITIM])
      were changed into phenylalanines. In conclusion, these data show the presence of
      functionally critical motifs within Fc gamma RII cytoplasmic tails. Fc gamma RIIa
      contains an ITAM involved in B-cell activatory functions, whereas the
      downregulatory activity of Fc gamma RIIb isoforms is linked to an ITIM.

PMID- 7718893
TI  - Role of gelsolin in the formation and organization of triton-soluble F-actin
      during myeloid differentiation of HL-60 cells.
AB  - Structurally and functionally distinct F-actin pools coexist with globular (G)
      actin in a variety of eukaryotic cells, including polymorphonuclear leukocytes
      (PMNs). In PMNs, a Triton-soluble F-actin pool (TSF) exists as short cytoplasmic
      filaments capped with gelsolin, while Triton-insoluble F-actin (TIF) is a three
      dimensional meshwork of F-actin associated with actin-binding protein 280 (ABP
      280), alpha-actinin, and tropomyosin. The unique association of gelsolin with the
      TSF suggests a role for gelsolin in creation or regulation of TSF. To evaluate
      gelsolin's role in TSF formation, the quantities of actin and gelsolin were
      determined by quantitative sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and immunoblots in uninduced HL-60 cells (U-HL-60) and
      in HL-60 cells induced to myeloid differentiation with 1.25% dimethyl sulfoxide
      for 4 to 5 days (I-HL-60). U-HL-60 cells contain 17.76 +/- 6.01 pmol actin per
      10(6) cells (TIF, 5.3 +/- 1.5; TSF, 2.17 +/- 0.37; G, 10.3 +/- 5.7; n = 5) and
      0.073 pmol gelsolin per 10(6) cells (TIF, 0; TSF, 0.002 +/- 0.005; G, 0.07 +/-
      0.01; n = 3), representing molar actin to gelsolin (A:G) ratios of 1,085:1 for
      TSF and 147:1 for G. After myeloid differentiation, the actin content increases
      1.80-fold (31.94 +/- 6.14 pmol/10(6) cells) equally in each actin pool (TIF, 9.36
      +/- 2.35; TSF, 3.29 +/- 0.62; G, 19.29 +/- 4.83). Gelsolin increases 2.4-fold
      overall (0.178 +/- 0.02 pmol/10(6) cells) but 19-fold in TSF (0.038 +/- 0.009)
      and only 1.9-fold in G pool (0.139 +/- 0.006), resulting in A:G ratios of 87:1 in
      TSF and 139:1 in G. The findings of an increase in TSF gelsolin with decreased
      A:G ratios (1,085:1 v 87:1) with myeloid differentiation suggest shortening of
      TSF filaments, while the A:G ratios of unbound gelsolin are unchanged (147:1 v
      139:1). Measurement of EGTA-resistant gelsolin/actin complexes in HL-60 cells
      shows that 95% to 100% of complexes exist in the TSF-actin pool only. These
      findings are consistent with a role for gelsolin in formation and organization of
      Triton-soluble F-actin. Furthermore, the apparent shortening of TSF-actin
      filaments with myeloid cellular differentiation and maturation may represent one
      mechanism of conversion of the nonmotile myeloblast to the motile PMN.

PMID- 7718894
TI  - Glycophorin SAT of the human erythrocyte membrane is specified by a hybrid gene
      reciprocal to glycophorin Dantu gene.
AB  - Previous studies of two unrelated Japanese families showed that two isoforms of
      glycophorin were associated with the expression of SAT antigen on the erythrocyte
      membrane. Here we report the molecular basis for one form of this MNSs-related
      surface marker that displayed an altered immunoblotting pattern. Evidence is
      presented that glycophorin SAT (GPSAT) is encoded by a hybrid gene resulting from
      unequal homologous recombination between GPA and GPB genes. Analysis of SAT
      genomic DNAs by Southern blots showed gross alterations in the glycophorin gene
      cluster. Those restriction fragments characteristic of the GPA 3' and GPB 5' ends
      were absent from the SAT homozygote and showed reduced intensity in SAT
      heterozygotes. Reticulocyte RNA polymerase chain reaction showed the presence in
      the SAT homozygote of GPSAT and GPE transcripts but no GPA and GPB transcripts.
      Direct sequencing of the amplified SAT cDNA showed that its sequence from exon I
      to exon IV was identical with the N allele of GPA, whereas its 3' portion,
      including exon V and exon VI, was derived from the GPB gene. The GPSAT protein in
      its mature form should contain 104 amino acid residues and bear a novel sequence,
      Ser-Glu-Pro-Ala-Pro-Val, encoded by the junction of GPA exon IV and GPB exon V.
      This sequence interfaces the extracellular and transmembrane domains and could be
      the epitope site of the SAT antigen. The formation of such a hybrid junction not
      only explains why SAT homozygous erythrocytes lack S, s, and U antigens but also
      shows a reciprocal arrangement with respect to the B-A hybrid GPDantu gene.

PMID- 7718895
TI  - Comparative evaluation of diepoxybutane sensitivity and cell cycle blockage in
      the diagnosis of Fanconi anemia.
AB  - Fanconi anemia (FA) is a clinically and genetically heterogenous disease that is
      usually diagnosed on the basis of chromosomal instability reflecting the
      hypersensitivity towards the DNA cross-linking agents diepoxybutane (DEB) and/or
      mitomycin C. A less well-known cellular feature that characterizes FA patients is
      an intrinsic cell cycle disturbance consisting of prolonged progression through,
      and arrest within, the G2 phase compartment of the cell cycle. In a collaborative
      blind study, we have evaluated 72-hour lymphocyte cultures from 66 patients with
      clinical suspicion of FA both for DEB sensitivity and cell cycle disturbance. A
      concordant result was obtained in 63 of 66 cases. Each of the 3 discordant, but
      only 1 of the concordant cases presented with overt leukemia. Seventeen cases
      were identified as classical FA because of their increased DEB sensitivity and G2
      phase blockage. Five cases showed a cell cycle disturbance but only borderline
      DEB sensitivity. These cases might represent atypical or nonclassical forms of
      FA. They would have been missed by cell cycle studies without concomitant DEB
      testing. Used in conjunction, cytogenetic and flow cytometric testing provide for
      the currently optimal diagnosis of FA in nonleukemic patients.

PMID- 7718896
TI  - Functional asplenia in hemoglobin SC disease.
AB  - The incidence of functional asplenia in sickle-hemoglobin C (SC) disease has not
      been defined, and the use of prophylactic penicillin to prevent life-threatening
      septicemia in this disorder is controversial. The percentage of red blood cells
      with pits (pit count) is a reliable assay of splenic function in other disorders
      but has not been validated in hemoglobin SC disease. To address these issues, we
      conducted a prospective, multicenter study of splenic function in persons with
      hemoglobin SC disease. Baseline clinical data were recorded, and red blood cell
      pit counts were performed on 201 subjects, aged 6 months to 90 years, with
      hemoglobin SC; 43 subjects underwent radionuclide liver-spleen scanning. Pit
      counts greater than 20% were associated with functional asplenia as assessed by
      liver-spleen scan, whereas pit counts less than 20% were found in subjects with
      preserved splenic function. Pit counts greater than 20% were present in 0 of 59
      subjects (0%) less than 4 years of age, in 19 of 86 subjects (22%) 4 to 12 years
      of age, and in 25 of 56 subjects (45%) greater than 12 years of age. Other
      subjects with hemoglobin SC, who had previously undergone surgical splenectomy,
      had higher pit counts (59.7% +/- 9.5%) than splenectomized subjects without
      hemoglobinopathy (38.5% +/- 8.8%) or with sickle cell anemia (20.5% +/- 1.9%; P <
      .001). Two subjects with hemoglobin SC disease (not splenectomized), ages 14 and
      15 years, with pit counts of 40.3% and 41.7% died from pneumococcal septicemia.
      These data indicate that functional asplenia occurs in many patients with
      hemoglobin SC disease, but its development is usually delayed until after 4 years
      of age. The pit count is a reliable measure of splenic function in hemoglobin SC
      disease, but values indicative of functional asplenia (> 20% in our laboratory)
      are higher than in other disorders. The routine administration of prophylactic
      penicillin to infants and young children with hemoglobin SC disease may not be
      necessary.

PMID- 7718897
TI  - Effects of hemoglobin concentration on deformability of individual sickle cells
      after deoxygenation.
AB  - To assess the role of intracellular hemoglobin concentration in the deformability
      of sickle (HbSS) cells after deoxygenation, rheologic coefficients (static
      rigidity E and dynamic rigidity eta) of density-fractionated individual sickle
      erythrocytes (SS cells) were determined as a function of oxygen tension (pO2)
      using the micropipette technique in a newly developed experimental chamber. With
      stepwise deoxygenation, E and eta values showed no significant increase before
      morphologic sickling but rose sharply after sickling. In denser cells, continued
      deoxygenation led to steep rises of E and eta toward infinity, as the cell
      behaved as a solid. The pO2 levels at which rheologic and morphologic changes
      occurred for individual SS cells during deoxygenation varied directly with the
      cell density. The extent of recovery in E and eta during reoxygenation varied
      inversely with the cell density. These results provide direct evidence that the
      intracellular sickle hemoglobin (HbS) concentration of SS cells plays an
      important role in their rheologic heterogeneity in deoxygenation and
      reoxygenation. The elevations of eta during pO2 alteration were greater than
      those of E, especially for the denser cells, suggesting the importance of the
      elevated dynamic rigidity in initiating microcirculatory disturbances in sickle
      cell disease.

PMID- 7718898
TI  - Four new mutations in the NADH-cytochrome b5 reductase gene from patients with
      recessive congenital methemoglobinemia type II.
AB  - Recessive congenital methemoglobinemia (RCM) due to NADH-cytochrome b5 reductase
      (cytb5r) deficiency leads to two different types of diseases. In the type I form,
      cyanosis is the only symptom, and the soluble enzyme is defective in red blood
      cells. In the type II form, cyanosis is associated with severe mental retardation
      and neurologic impairment; the enzymatic defect is systemic, involving both
      soluble and membrane-bound isoforms. We characterized mutations responsible for
      cytb5r deficiency in three unrelated patients with severe RCM type II. The first
      patient presented a homozygous exon 5 skipping. The only mutation detected was a
      homozygous G to C transversion at position +8, downstream from the 5' splice site
      of exon 5. We suggest that this unusual mutation might be responsible for the
      abnormal splicing of the primary transcripts, resulting in frameshift with
      premature STOP codon. The second mutation found corresponds to a homozygous C to
      T transition changing the Arg-218 codon to a premature STOP codon in exon 8. The
      third case was a compound heterozygote, carrying two different mutant alleles in
      the cyb5r gene. One allele presented a missense mutation with replacement of Cys
      203 (TGC) by Arg (CGC) in exon 7. The second allele carried a 3-bp deletion (TGA)
      of nucleotides 815 to 817, modifying two contiguous codons in exon 9 of the cDNA
      with loss of Met-272. These results confirm the genetic polymorphism of cytb5r
      gene mutations identified in RCM type II, as observed for the mutations described
      in the RCM type I, and shed light on the molecular bases of the two different
      diseases associated with cytb5r deficiency.

PMID- 7718899
TI  - Allogeneic bone marrow transplantation for chronic myeloid leukemia in first
      chronic phase: a randomized trial of busulfan-cytoxan versus cytoxan-total body
      irradiation as preparative regimen: a report from the French Society of Bone
      Marrow Graft (SFGM).
AB  - From March 1988 to March 1991, 19 French bone marrow transplant (BMT) centers
      participated in a prospective randomized trial comparing two conditioning
      regimens for patients with chronic myeloid leukemia transplanted in first chronic
      phase with an HLA identical sibling donor. A total of 120 consecutive patients
      were randomized to receive either 120 mg/kg of cyclophosphamide followed by total
      body irradiation (CY-TBI; n = 55) or 16 mg/kg of busulfan followed by 120 mg/kg
      of CY (BU-CY; n = 65). Two different TBI regimens were used. Thirteen patients
      received a 10-Gy single-dose TBI (SDTBI), and 42 received a fractionated TBI
      (FTBI). Median time between diagnosis and BMT was 315 days. Overall 5-year
      actuarial survival was 62.9% (65.8% +/- 12.5% for CY-TBI and 60.6 +/- 11.7% for
      BU-CY; P = .5), and overall disease-free survival was 55% (51% +/- 14% for CY-TBI
      and 59.1% +/- 11.8% for BU-CY; P = .75). All patients conditioned with CY-TBI
      experienced sustained engraftment; in contrast, 4 of 65 patients conditioned with
      BU-CY rejected the graft (P = .18). There was no significant statistical
      difference between the two groups regarding transplant-related mortality (29% for
      CY-TBI and 38% for BU-CY; P = .44). So far, with a median follow up of 42 months,
      11 patients have relapsed; 9 relapses occurred after CY-TBI, mostly after FTBI (8
      of 9) and 2 after BU-CY (P = .02). The actuarial risk of relapse was 4.4% +/-
      6.7% after BU-CY, 11.1% +/- 20.8% after SDTBI, and 31.3% +/- 18.1% after FTBI (P
      = .039). In addition, independently of the conditioning regimen, the increase of
      posttransplant immunosuppression in 16 patients with an anti-interleukin-2
      receptor monoclonal antibody (MoAb) in addition to a short course of methotrexate
      and cyclosporine was shown to increase the actuarial risk of relapse (57% +/- 30%
      with MoAb v 9% +/- 7.3% without MoAb; P = .001). We conclude that BU is an
      acceptable alternative to TBI for patients with chronic myeloid leukemia in first
      chronic phase receiving BMT from HLA identical sibling donors. Both BU-CY and CY
      TBI regimens gave similar transplant-related mortality, and the antileukemic
      efficiency of BU-CY regimen was either similar or even higher than that of CY
      TBI.

PMID- 7718900
TI  - Interleukin-8 induces rapid mobilization of hematopoietic stem cells with
      radioprotective capacity and long-term myelolymphoid repopulating ability.
AB  - Interleukin-8 (IL-8) belongs to a family of chemoattractant cytokines involved in
      chemotaxis and activation of neutrophils. As in vivo administration of IL-8
      induces granulocytosis and the release of immature white blood cells into the
      circulation, we assessed a possible mobilizing effect of IL-8 on myeloid
      progenitor cells. IL-8 was administered at intraperitoneal doses ranging from 0.1
      to 100 micrograms per mouse to female Balb/C mice (aged 8 to 12 weeks; weight, 20
      to 25 g). Animals were killed at time intervals ranging from 1 to 240 minutes
      after IL-8 administration, and blood, bone marrow, and spleen cells were
      harvested. Injection of 30 micrograms IL-8 resulted in an increment from 25 +/- 9
      to 418 +/- 299 granulocyte-macrophage colony-forming units (CFU-GM) per
      milliliter blood at 15 minutes after a single intraperitoneal injection. Sixty
      minutes after the injection of IL-8, the numbers of circulating CFU-GM per
      milliliter blood had almost returned to pretreatment values (82 +/- 39 CFU-GM per
      milliliter). A dose of 100 micrograms IL-8 per animal did not result in a further
      increment in the number of circulating CFU-GM. Transplantation of 5 x 10(5) blood
      derived mononuclear cells (MNC) obtained at 30 minutes after IL-8 injection (30
      micrograms) resulted in 69% survival of lethally irradiated (8.5 Gy) recipients
      at 60 days versus 22% for animals transplanted with an equal number of nonprimed
      blood-derived MNC. Transplantation of 1.5 x 10(6) MNC obtained from IL-8-treated
      donors resulted in 100% survival. Six months after transplantation, female
      recipients of MNC derived from IL-8-treated male donors were killed, and
      chimerism was determined in bone marrow, spleen, and thymus using a Y chromosome
      specific probe and fluorescent in situ hybridization (FISH). The majority of bone
      marrow, spleen, and thymus cells (83% +/- 25%, 89% +/- 5%, and 64 +/- 28%,
      respectively) consisted of Y chromosome-positive cells, showing that the IL-8
      mobilized cells had myelolymphoid repopulating ability. We conclude that IL-8 is
      a cytokine that induces rapid mobilization of progenitor cells and pluripotent
      stem cells that are able to rescue lethally irradiated mice and that are able to
      completely and permanently repopulate host hematopoietic tissues.

PMID- 7718901
TI  - Soluble intercellular adhesion molecule-1 correlates with markers of disease
      activity in B-cell chronic lymphocytic leukemia.

PMID- 7718902
TI  - An international histiocytic language.

PMID- 7718903
TI  - Evaluation of CD38 as target for immunotherapy in multiple myeloma.

PMID- 7718904
TI  - alpha-Interferon and hypereosinophilic syndrome with trisomy 8: karyotypic
      remission.

PMID- 7718905
TI  - [Maternal partial attachment for one of a pair of twins and the influence of
      childcaring environments].
AB  - The birth of twins is associated with an increased risk of child abuse and
      neglect. It is reported that one twin rather than both twins tend to be abused in
      most of the abused twin children and most of abusers are the mothers in Japan.
      This means that maternal attachment feeling to one twin differs from the other
      one. In this study, we have conducted a mailed questionnaires survey for 123
      mothers of twins in order to clarify the relationship between the maternal
      attachment feeling to their twin children and various environmental-family
      factors. The following results were obtained. 1) Of 123 mothers, 8 (6.5%)
      reported that they didn't equally attach themselves to both of twins. 7 of these
      8 pair of twins were less than 3 years of age. 2) Mothers who didn't equally
      attach themselves to both of twins showed significant poor sleeping condition and
      severe fatigue (physical and mental), compared with mothers who equally attached
      themselves to twins. There was a significant tendency that mothers didn't equally
      attach themselves to twins when one twin was handicapped. Especially, the average
      sleeping time for mothers who didn't equally attach themselves to twins was 5.43
      hours a day, while for mothers who equally attached themselves to twins, 6.39
      hours. Concerning the frequency of sleeping breaks during the night, 57.1% of
      mothers who didn't equally attach themselves to both of twins reported 3 and more
      times, while 23.1% of mothers who equally attached themselves to twins reported 3
      and more times.

PMID- 7718906
TI  - [Antenatal complications in triplet pregnancies and birth weights of triplets
      compared with those of twins].
AB  - A mailed questionnaire survey was conducted on 96 mothers of triplets to study
      antenatal complications in triplet pregnancies and birth weights of triplets, and
      compared to 122 controls recruited from mothers of twins. The following results
      were obtained. 1) Antenatal complications occurred in approximately 80% of both
      triplet and twin pregnancies. In the triplet pregnancies the incidence of toxemia
      of pregnancy and anemia was 25.0% and 47.9%, respectively. There was no
      significant difference in the incidence of antenatal complications, toxemia of
      pregnancy and anemia between triplet and twin pregnancies. On the other hand, the
      incidence of preterm labor and threatened miscarriage was higher in triplets
      (70.8% and 34.4% respectively) than in twin pregnancies (45.9% and 12.3%
      respectively). 2) The mean birth weight was 1831.7 g for each individual triplet
      and 5495.0 g for each triplet set. In triplets, 94.7% were low in birth weight (<
      2500 g). 3) The antenatal complications of preterm labor and threatened
      miscarriage in triplet pregnancies have increased since 1990 in Japan. The
      frequency of toxemia of pregnancy and anemia did not particularly change
      significantly during the surveyed years. However, mean birth weight for each
      individual triplet showed a tendency to decrease from year to year (1978-1989,
      1934.5 g; 1990-1991, 1900.3 g; 1992-1993, 1741.1 g).

PMID- 7718907
TI  - [Analysis of factors related to the recent decline in birth rate in Japan].
AB  - This study was undertaken in an attempt to determine whether regional differences
      exist for those factors which have affected the decline in the total fertility
      rate in Japan between 1970 and 1990. Age Stratified analysis of vital statistics
      of the 20 to 39-year-old female population for the 46 prefectures was performed,
      and evaluated in relation to urbanization. The parameters examined were birth
      rate, percentage of married women, rates of birth by married women, and
      percentage of the work force in the service industry. The results were as
      follows. 1. Characteristic changes were noted in birth rates for females between
      25 and 29 years of age. The reasons are that average marriage age for females
      shifted from 20-24 to 25-29, causing the birth rates for females between the ages
      of 25 to 29 years to decline, while not uniformly, but with some regional
      differences among the 46 prefectures. 2. Urbanization has had a significant
      effect on the declining birth rate for females grouped by age. The advance of the
      urbanization process in each prefecture is directly related to the decline in the
      birth rates for females between 20 to 24 years and 25 to 29 years. The extent of
      urbanization in each prefecture is inversely related to the rate of birth by
      married women and the percentage of married women between age 20 to 24 and 25 to
      29 in that prefecture. The trend toward delaying marriage and childbirth in the
      urbanized prefectures appeared to be a major factor leading to the decline in the
      total fertility rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718908
TI  - [Annual trends in incidence of congenital anomalies in Tokyo metropolitan
      hospitals].
AB  - Annual incidence rates of selected congenital anomalies were calculated between
      January 1979 and December 1992 among all births in Tokyo metropolitan hospitals.
      Congenital anomalies were observed in 1989 infants, or about 1.5% of the 132,091
      births. The characteristics of the study population were identical to that for
      the total births in Tokyo. Incidence rates showed practically no secular changes,
      indicating stationary trends during the 14 years monitored.

PMID- 7718909
TI  - [A critical situation of the prevalence of echinococcosis (alveolar hydatid
      disease)--necessity of immediate action for the prevention].

PMID- 7718910
TI  - [Health locus of control and acquisition of health-related information].
AB  - Relationships between acquisition of health-related information and Health Locus
      of Control (HLC) were investigated in 204 women aged 29-45 years, using Horige's
      Japanese version of Health Locus of Control (JHLC) Scales. The acquisition
      behavior of health-related information was obtained from the question "How often
      do you get health-related information by newspaper, television or magazine?" The
      results were as follows: 1) Women who perceived the information related directly
      to their personal health, acquired health-related information more often than
      those who did not perceive personal application of the information. 2) The
      technical school or junior college graduate group had the most health-related
      information acquisition scores. 3) The university graduate group had fewer Chance
      HLC beliefs and Supernatural HLC beliefs. 4) Family HLC mean scores were
      significantly higher in the "high family value" group than in the "high health
      value" group. 5) Internal HLC mean scores were significantly higher in those self
      rated as "very healthy" than in those self-rated as "healthy" group. 6) Women
      acquiring health-related information the most had Internal HLC mean scores
      significantly higher than the others. Health-related information acquisition
      scores correlated significantly with Internal HLC mean scores and Family HLC mean
      scores.

PMID- 7718911
TI  - [The relationship between serum dehydroepiandrosterone sulfate levels and factors
      associated with cardiovascular diseases: a cross-sectional study in Japan].
AB  - To explore the relationship between serum DHEAS levels and blood pressure,
      obesity, smoking habits and drinking habits associated with onset of
      cardiovascular disease, we examined serum DHEAS levels in 90 males and 183
      females, aged 35 to 62 years, who participated in a mass health examination
      conducted in a town of Aichi prefecture in 1992. The results were as follows. 1.
      Serum DHEAS levels were significantly higher in males than in females and
      decreased with age both sexes. 2. Age-adjusted serum DHEAS levels for both sexes
      decreased with blood pressure and BMI. 3. There were no apparent significance
      between age-adjusted serum DHEAS levels and smoking habits, whereas age-adjusted
      serum DHEAS levels were higher in groups of intake of ethanol volume 1-29 g/day
      than in the groups of intake of more than and less than ethanol volume 1-29
      g/day. 4. Age-adjusted serum DHEAS levels were significantly decreased with the
      rise of sum of factors chosen as risk factor of cardiovascular disease disease in
      this study. It was suggested that serum DHEAS levels might be useful as an index
      of accumulation of risk factors of cardiovascular disease. Further studies should
      be performed to establish the possibilities as an index of genesis and prevention
      of cardiovascular disease.

PMID- 7718912
TI  - [Body density assessment utilizing skinfold thickness and age in Japanese women].
AB  - A study was conducted to investigate the validity of skinfold-based prediction
      equations for body density (g/ml) by Nagamine and Suzuki (1964), and to formulate
      more convenient and more useful equations for predicting body density from
      skinfold and age in women. Subjects of the study were 512 healthy women aged 18
      66 years in or near Nagasaki City. The dependent variable in the multiple
      regression equation, body density, was determined by hydrostatic weighing.
      Independent variables included eight skinfolds, the sum of two skinfolds
      (triceps, subscapular), the sum of three skinfolds (triceps, subscapular, and
      abdominal), age, and body surface area. Skinfolds were measured with an Eiken
      model skinfold caliper. Age (mean 30.1, range 18-66 yrs.), weight (mean 52.6,
      range 38.0-83.3 kg), height (mean 157.0, range 142.0-172.0 cm), and body density,
      (mean 1.04125, range 0.98806-1.08650 g/ml) were also recorded. Percent body fat
      was calculated using the formula by Brozek et al. and ranged from 6.4% to 48.3%.
      Multiple correlation coefficients (MR) and standard error (SE) of 10 regression
      equations (A-J) for predicting body density in women were compared. The best
      fitting and the most convenient prediction equation for body density was equation
      E. The regression equation developed for predicting body density was: body
      density = 1.07931-0.00059 x sum of three skinfolds(mm)-0.00015 x age (MR = 0.77
      and SE = 0.0089). The equation was cross-validated on a different sample of 46
      women. The correlation coefficient between predicted and hydrostatically
      determined body density was 0.813 (p < 0.001). Equation-E (Tahara's equation)
      appears to be useful in body density analysis particularly when the subjects are
      Japanese women, aged 18-50 yrs, with percent body fat 17 to 34%.

PMID- 7718913
TI  - [Relationship of dietary intake of sodium, potassium, calcium and magnesium to
      blood pressure].
AB  - Dietary intake of sodium (Na), potassium (K), calcium (Ca) and magnesium (Mg)
      from measured food intake, and urinary Na and K excretions estimated by analyzing
      the second voided morning urine were analyzed for correlations to each other and
      to blood pressure in 57 males and 90 females (average age of 53 years).
      Significant positive correlations were found between systolic blood pressure and
      urinary Na/K ratio, dietary Ca/Mg ratio and body mass index after adjustment for
      age. Diastolic blood pressure was also positively correlated to these variables.
      By multiple regression analysis, the coefficients for age and urinary Na/K and
      dietary Ca/Mg ratios were all statistically significantly associated with
      systolic and diastolic blood pressure. Dietary Ca/Mg ratio was negatively
      correlated with rice, beans and fish intake, and urinary K excretion positively
      correlated with fish and green vegetable intakes by the same analysis. These data
      suggest that the dietary Ca/Mg ratio--but not magnesium singly--as well as aging
      and urinary Na/K ratio were among important factors related to blood pressure.

PMID- 7718914
TI  - Order-disorder in T, T', and T* phase: superconductors and related materials.
AB  - After reviewing microstructural studies on superconducting materials showing T,
      T', and T* structural types, results are presented on the microstructure of some
      n-type superconductors and related materials prepared with accurate control of
      the oxygen stoichiometry. Electron microscopy is used to describe the ordering of
      interstitial oxygen defects in T-type La2NiO4 + delta leading to the formation of
      the n = 2 term of a homologous series with the general formula La8nNi4nO16n + 1.
      Structural transitions and superstructure formation in the Pr2-x-yCexSryCuO4
      delta system are reported, where T, T', and T* phases are isolated as a function
      of both Ce and Sr content.

PMID- 7718915
TI  - Transmission EELS of oxide superconductors with a cold field emission TEM.
AB  - Electron energy loss spectrometry (EELS) with a cold field emission gun (cFEG)
      transmission electron microscope (TEM) is implemented to analyze the evolution of
      the electronic structure and dielectric function of oxide superconductors. The O
      K core loss spectra of p-type doped oxide superconductors are analyzed in terms
      of holes formation on oxygen sites, while low loss spectra are analyzed for free
      carrier plasmas, other spectral excitations, and their crystallographic
      confinement. It is illustrated that the transmission EELS with a cFEG TEM very
      much complement soft X-ray absorption spectroscopy and optical spectroscopy, with
      the added advantages of high spatial resolution (approximately 1-100 nm), and is
      compatible with other analytical, diffraction, and imaging techniques, which are
      readily available in a cFEG TEM.

PMID- 7718916
TI  - Crystal structure, chemical composition, and extended defects of the high-Tc
      (Bi,Pb)2Sr2Ca(n)-1CunO4 + 2n + delta compounds.
AB  - This paper summarizes results obtained by high-resolution transmission electron
      microscopy on the crystal structure and microstructure of the (Bi,Pb)2Sr2Ca(n)
      1CunO4 + 2n + delta high-Tc superconducting oxides. The experimental basis for
      the work presented here are high-resolution structure images obtained at ultra
      thin (3 nm) areas of carefully prepared transmission electron microscope (TEM)
      samples. The analysis was carried out on a 400 kV TEM equipped with a pole piece
      yielding 0.17 nm point-to-point resolution. From the images obtained the
      projected crystal potential of the cations can be extracted directly, as
      confirmed by detailed image simulation. Structural analysis of the oxygen
      sublattice remains an unsolved problem by high-resolution TEM (HRTEM), mainly
      because of the small scattering factors, and thus the contribution of the oxygen
      sublattice to the image contrast is small. The (BiPb)2Sr2Ca(n)-1CunO4 + 2n +
      delta phases are modulated structures that can be understood as an average
      structure plus a superimposed displacement field. The crystal structure consists
      of BiO double layers and perovskite-type cuboids (containing Sr, Ca, Cu, and O),
      which are sandwiched between the BiO double layers. The displacement field can be
      directly analyzed by HRTEM, and the largest displacement amplitudes of 70 pm were
      determined for the Bi atoms in the n = 1 compound. The chemical composition of
      the n = 2 and n = 3 compounds was determined by EDX in the TEM for the cation
      sublattice. A significant (Ca + Sr) deficiency (approximately 10%) with respect
      to Cu was found. The (Sr + Ca)/Cu mole fraction ratio was 1.31 for the Bi-2212
      phase and 1.14 for the Bi(Pb)-2223 phase. The oxygen content cannot be determined
      by EDX in the TEM with the accuracy necessary for a correlation with electrical
      and superconducting properties. The defect structure present in these materials,
      that is, intergrown lamellae with different crystal structures and equal or
      different chemical compositions, stacking faults, and grain boundaries, is
      summarized. The importance of grain boundaries for understanding and improving
      superconducting properties is emphasized.

PMID- 7718917
TI  - Freeze-fracture study of Bodo sp. (Kinetoplastida: Bodonidae).
AB  - Freeze-fracture technique was used to analyse the structure of conventionally
      fixed and quickly frozen Bodo sp., a free-living kinetoplastid. In the former
      method, chemically fixed and cryopreserved cells presented a corrugated membrane
      pattern in the flagella and cell body surfaces. In the latter, however, replicas
      from quickly frozen unfixed flagellates showed membranes with a smoother aspect,
      allowing the observation of intramembranous particles (IMPs) on the fracture
      faces, hardly detectable in previously fixed samples. The IMPs were randomly
      distributed throughout the cell surface, except in the sparsely seen short IMP
      rows.

PMID- 7718918
TI  - Interaction of colloidal gold-labelled glucosylated albumin with endothelial cell
      monolayers: comparison between cryofixation and glutaraldehyde fixation.
AB  - Bovine aortic endothelial cells (BAEC) were exposed to glucosylated albumin-gold
      complexes (GgA), and the distribution of the tracers was compared after
      cryofixation and after glutaraldehyde fixation. Morphometric analysis revealed
      differences in the GgA distribution depending upon the method of fixation used.
      In BAEC monolayers cryofixed after 3 min of incubation with GgA, tracer was
      observed in predominately apically located vesicular elements. After 16 min of
      incubation, all vesicular elements were labelled, and multivesicular bodies were
      the prominent labelled structure. In contrast, chemically fixed monolayers
      exhibited a heterogeneous distribution of GgA within vesicular profiles after 3
      min and 16 min of GgA incubation. The differences in tracer distribution
      depending upon the fixation method must be resolved before the mechanism of
      vesicle-mediated endothelial cell transport function is defined and universally
      accepted.

PMID- 7718919
TI  - Microstructures in high-Tc Bi(Pb)-family 2212 superconductors as revealed by
      scanning and transmission electron microscopy.
AB  - Microstructures of Bi(Pb)-family 2212 superconductors, which were prepared by a
      sol-gel method with three different compositions, were examined mainly by
      scanning and transmission electron microscopy. The magnetization of the specimens
      strongly depends on the ratio between Bi and Pb content, while Tc is almost
      constant. In specimen 1, prepared with the nominal composition of Bi/Pb = 9/1,
      small grains of 2212 phase are formed with a minor fraction of some impurity
      phases. In specimen 2, with Bi/Pb = 17/3, which is optimum from the viewpoint of
      magnetization, large grains of the 2212 phase are formed during heating at 800
      degrees C, also with the impurity phases. In specimen 3, with Bi/Pb = 8/2, the
      2212 grains are divided by layers of (Bi0.86, Pb0.14) (Ca0.7, Sr0.3)Ox. Moreover,
      plate-like 2212 crystals are severely bent so that small cracks appear often with
      an inclusion of amorphous substance being rich in Ca and Pb. These layers and
      cracks must degrade the magnetization. A modulated structure of Bi-type is formed
      in the 2212 grains of specimens 1 and 2, while not only Bi-type but also Pb-type
      are formed in specimen 3. The wavelength of Bi-type is different for each
      specimen.

PMID- 7718920
TI  - A method for preparation of immobilized cells and tissues for light and electron
      microscopy studies.

PMID- 7718921
TI  - Preventing jailhouse suicides.
AB  - Psychiatric consultants to city and county jails are confronted with the
      challenge of preventing jailhouse suicides, a problem of national scope. Suicide
      prevention programs in jails must emphasize screening and identification,
      psychological support, observation, disarmament, clarity and consistency, and
      diagnosis, treatment, and/or hospitalization. Exactly how these principles are
      formulated and implemented will depend on the unique circumstances of each jail.
      Finally information is presented as evidence that a program that embodies these
      principles can effectively reduce the number of suicides in a jail where the
      average daily census has increased from fewer than 400 to greater than 900 in the
      past six years.

PMID- 7718922
TI  - The Munchausen syndrome in civil forensic psychiatry.
AB  - The diagnosis of Munchausen syndrome requires that a patient intentionally
      produce or feign physical symptoms with a psychological need to assume the sick
      role. To differentiate the disorder from malingering one must document the
      absence of an external incentive for the patient's behavior. Although malingering
      is a major topic of interest in forensic psychiatry, there has been no literature
      that looks at the Munchausen syndrome presenting in the civil forensic setting.
      This paper reports on two cases of the Munchausen syndrome that occurred in the
      areas of medical malpractice and workers' compensation. The cases highlight how
      the psychiatrist should approach these cases in the civil forensic setting. The
      malpractice case also illustrates how the disorder is viewed by an appellate
      court.

PMID- 7718923
TI  - Munchausen syndrome by proxy in false allegations of child sexual abuse: legal
      implications.
AB  - A review of the literature regarding Munchausen syndrome by proxy in relation to
      allegations of child sexual abuse is presented. Problems in the diagnosis of
      Munchausen syndrome by proxy in these cases can be the result of a failure to
      consider that the allegations may be false, legal issues surrounding the child's
      testimony, and other biases in professional and legal attitudes towards
      allegations of sexual abuse. A proposal for a more stringent standard of care is
      made. Treatment of Munchausen syndrome by proxy is best effected by case
      management, with the person who made the diagnosis managing the case throughout
      the treatment. This person should act as liaison to relay information between all
      the parties involved.

PMID- 7718924
TI  - Transsexualism and the law.
AB  - Transsexuals pose dilemmas for the law in (a) defining a male or a female; (b)
      deciding what partners are legally acceptable for marriage; (c) assessing the
      best interests of children after divorce; (d) interpreting employment
      discrimination based on gender or handicap; (e) permitting public cross dressing;
      (f) reviewing third-party reimbursement for medical procedures that may be deemed
      cosmetic or experimental; (g) determining eligibility for sports competition; (h)
      meeting military needs; and (i) determining socially and medically acceptable
      treatment in prison. Leading law cases are reviewed in each area, with commentary
      on relevant research findings.

PMID- 7718925
TI  - Involuntary medication of patients who are incompetent to stand trial: a review
      of empirical studies.
AB  - Involuntary administration of antipsychotic medication to pretrial criminal
      defendants raises important and controversial questions. These questions arise
      especially with defendants who have been adjudicated as incompetent to stand
      trial and who require medication to be restored to trial-competency and return to
      face their pending criminal charges. This subject has been fiercely debated for
      decades, but it has received little empirical investigation. We review here the
      known empirical studies that have looked at the use of involuntary medication for
      this population of individuals. The following nine conceptual areas are explored:
      subject selection, definition of 'refusal' and related terms, frequency of
      refusal, characteristics of refusers, reasons for treatment, reasons for refusal,
      type and outcome of the review of the refusal, outcome of treatment in the
      hospital, and outcome of the criminal charges. Relevant findings are reviewed.
      Methodological limitations call for more research in this area.

PMID- 7718926
TI  - Clinical vampirism: blending myth and reality.
AB  - Vampires arouse strong popular interest and attract large print and film
      audiences. Their influence is also notable in clinical vampirism, a rare
      condition described in the forensic literature covering some of humanity's most
      shocking behaviors. Definitions of vampirism involve aspects of necrophilia,
      sadism, cannibalism, and a fascination with blood. Its relationships with
      established diagnostic categories, particularly schizophrenia and psychopathy,
      are also examined and illustrated by the presentation of a "modern" vampire. As
      myth and reality are disentangled, clinical vampirism reveals the complex mother
      child dyad's blood ties running amok.

PMID- 7718928
TI  - Community placement for insanity acquittees: a preliminary study of residential
      programs and person-situation fit.
AB  - The present study, one of the first of its kind, describes the characteristics of
      community living placements for insanity acquittees conditionally released
      following hospitalization, along with the "fit" between living placement and
      individual characteristics. Although the small number of insanity acquittees (n =
      13) and community placements (n = 9) precluded meaningful statistical analyses of
      results, the study provides a model for studying the characteristics of
      placements as well as personal characteristics of acquittees, and the interaction
      between the two. It also suggests the possible importance of this interaction,
      operationalized as "fit" between characteristics and placement. Consistent with
      research findings for other criminal defendants and for nonforensic psychiatric
      patients released from hospitalization, a better fit between acquittee and
      community placement may be associated with increased likelihood of success on
      conditional release.

PMID- 7718927
TI  - Staff gender and risk of assault on doctors and nurses.
AB  - Clinical staff on acute psychiatric inpatient units often are asked to provide
      care for potentially violent patients. Documentation of which staff are at
      greatest risk of being assaulted is a necessary step in developing interventions
      to reduce that risk. The present study evaluated the relationship between staff
      gender and the risk of becoming a victim of assault while taking into account the
      professional discipline of the staff victims. The sample included all medical
      staff (n = 120) and nursing staff (n = 83) who worked on a short-term psychiatric
      unit between August 1988 and May 1991. Seventy-two percent of the medical and
      nursing staff were female and 28 percent were male. Five hundred ten assaults
      were directed toward medical and nursing staff during the study period. Staff
      gender was not significantly associated with the risk of being a victim of
      violence for the staff as a whole, the doctors, or the nurses. Staff discipline,
      however, was strongly associated with risk of assault. Nurses as a group were
      significantly more likely to be assaulted than were doctors. The findings suggest
      that violent behavior is a significant occupational hazard on acute inpatient
      units, and that the role relationship with the patient is more important than the
      gender of the clinician as a predictor of who is most likely to be assaulted. The
      authors discuss the implications of the findings for administrative decisions
      regarding staffing.

PMID- 7718929
TI  - Guide to identifying and correcting decision making errors in mental disability
      practice.
AB  - Presented is a practical and theoretical guide to help practitioners identify and
      alleviate decision making errors. Common decision making and judgment errors are
      inventoried and presented as deviations from the scientific method. Also
      presented is evidence of judgmental inaccuracies in critical areas. A modus
      operandi called the "lab report" method is offered as a way to avoid making some
      of these errors. The lab report method is a way of conducting forensic
      evaluations in a more rational and scientific way, in much the same way as a good
      researcher would conduct a study. Using this method the clinician, like the
      researcher, uses clearly articulated alternative hypotheses with specifically
      operationalized measures. Data are collected in a systematic way to test each
      hypothesis, and consistent feedback is sought. Throughout the paper the
      scientific method is reviewed; evidence of problems applying it in clinical
      practice are presented, as are ways of overcoming these problems.

PMID- 7718930
TI  - The patient self-determination act and psychiatric care.
AB  - The Patient Self-Determination Act (PSDA) has been in effect since December 1,
      1991. The primary purpose of the PSDA is to promote patient awareness of advance
      directives. Many psychiatrists are unaware of the PSDA and its requirements or
      believe that the PSDA does not apply to psychiatric facilities and patients. In
      this article the requirements of the PSDA are reviewed. Potential applications of
      advance directives in psychiatric care are discussed and problem areas are
      identified. It is suggested that psychiatrists take an active role in the
      implementation of the PSDA.

PMID- 7718931
TI  - An analogue study of the factors influencing competency decisions.
AB  - Forensic psychiatrists who were members of the American Academy of Psychiatry and
      the Law analyzed case histories to make a competency or incompetency decision.
      The case histories were created to alter background information, diagnostic
      information, information about the defendants' understanding of the adversarial
      process, courtroom behavior, and the nature of the crime. The information that
      had the most influence on the decisions of the forensic psychiatrists included
      the cognitive status of the defendant, psychotic features, courtroom behavior,
      and understanding of the adversarial process. Relationship with the lawyer,
      alcohol/drug use history, psychiatric history, and criminal history had less
      influence. The forensic psychiatrists tended to "error" toward a decision for
      competency unless compelling evidence was presented to the contrary.

PMID- 7718932
TI  - Medication refusal--clinical picture and outcome after use of administrative
      review.
AB  - To determine the effectiveness of the Administrative Review as a tool in
      discerning which patients who refuse medication should be medicated
      involuntarily; define characteristics of voluntarily and involuntarily committed
      patients who refuse medication; and compare posttreatment status of patients who
      successfully refused medication with those who were administered medication
      involuntarily.

PMID- 7718933
TI  - Factors associated with dangerous behavior in forensic inpatients: results from a
      pilot study.
AB  - This study was designed to identify risk factors associated with violence within
      a forensic inpatient hospital setting. The primary purpose was to develop a
      screening tool to aid in the rapid identification of patients requiring high
      versus low security ward placement. Subjects included 232 consecutive admissions
      during a five-month period to a 300-bed forensic division within a public-sector
      psychiatric hospital. Demographic, historical, and current clinical variables
      were collected, and dangerous behaviors were documented by nursing staff on a
      daily basis. The associations between dangerous outcomes and various risk factors
      were examined using chi-square or t tests, as appropriate. Stepwise logistic
      regression analysis was performed to assess the contribution of each risk factor
      significantly associated with violent behavior. A strong association was found
      between 10 risk factors and the incidence of violence in our forensic population.
      These factors included current clinical factors (grossly inappropriate behavior
      observed on the ward, an assessment of current escape risk); historical factors
      (psychiatric hospitalization history, criminal history variables, and a self
      report of prior violence); and one demographic variable (length of stay). Of the
      10 risk factors then included in the stepwise regression analysis, four
      contributed significantly to the final predictive model. Grossly inappropriate
      behavior, patient self-report of prior violence, history of psychiatric
      hospitalization, and a history of 10 or more prior psychiatric hospitalizations
      were most predictive of a violent outcome. Although situational and environmental
      variables also must be incorporated into final assessments and decisions, the
      identified significant variables can provide an additional tool in the rapid
      assessment of violence potential.

PMID- 7718934
TI  - Psychiatric stigma in correctional facilities.
AB  - While legislatively sanctioned discrimination against the mentally ill in general
      society has largely disappeared, it persists in correctional systems where
      inmates are denied earn-time reductions in sentences, parole opportunities,
      placement in less restrictive facilities, and opportunities to participate in
      sentence-reducing programs because of their status as psychiatric patients or
      their need for psychotropic medications. The authors discuss the prevalence of
      such problems from detailed examinations of several correctional systems and from
      the results of a national survey of correctional medical directors.

PMID- 7718935
TI  - Single-photon emission computed tomography of the brain in acute mania and
      schizophrenia.
AB  - Single-photon emission computed tomography (SPECT) imaging with n
      isopropyliodoamphetamine (IMP) was performed on 11 patients with bipolar mania,
      21 acute schizophrenics, and 15 healthy control subjects. Subjects were evaluated
      with neuropsychological tests and psychiatric rating scales. SPECT brain studies
      were blindly evaluated to assess the degree of radiopharmaceutical uptake in
      three neuroanatomical regions of interest in each hemisphere. All the control
      subjects, 1 manic patient, and 1 schizophrenic patient had normal brain SPECT
      uptake patterns. The scans of all others were read as abnormal. Hypofrontality
      was noted in some schizophrenics and maniacs. A significant increase in tracer
      uptake in temporal lobes was observed in both patient groups, more prominently in
      the manic patients. Increased and decreased basal ganglia uptake was also
      observed in patients. Both manic and schizophrenic patients showed cortical
      tracer heterogeneity of varying degree. The patterns of cerebral SPECT uptake
      seen in these acute psychoses were not specific for a diagnosis, but may be
      associated with dimensions of psychopathology. Because the patterns are different
      from those seen in cerebrovascular disease and the dementias, they may prove to
      be helpful in differential diagnosis.

PMID- 7718936
TI  - Evaluation of the ventricular system in adults by transcranial duplex sonography.
AB  - Transcranial duplex color-flow sonography provides visualization of intracranial
      structures, and measures angle-corrected blood flow velocity in the basal
      cerebral arteries of adults. In 44 patients with central nervous system disease,
      the oblique diameters of the third and the middle part of the lateral ventricle
      were measured by transcranial duplex color-flow sonography using a system with a
      2.5-MHz transducer, and compared to computed tomography measurements. The
      correlation coefficients for the third and lateral ventricle measurements were r
      = 0.83 (p < 0.0001, N = 38) and 0.73 (p < 0.0001, N = 78), respectively. A second
      investigation was performed by transcranial duplex to evaluate intraobserver and
      interobserver reproducibility. The correlation coefficient representing
      interobserver reproducibility in 27 patients was r = 0.87 (p < 0.0001, N = 47)
      for the lateral ventricle and r = 0.9 (p < 0.0001, N = 49) for the third
      ventricle. The intraobserver reproducibility correlation coefficient was r = 0.93
      (p < 0.0001, N = 22) for the lateral ventricle in 12 patients. In 49 healthy
      volunteers the oblique diameters of the lateral and third ventricles were age
      dependent, measuring 16.7 +/- 2.3 mm and 4.8 +/- 1.9 mm, respectively, in those
      younger than 59 years, compared to 19.0 +/- 2.9 mm and 7.6 +/- 2.1 mm in those 60
      years or older. Therefore, transcranial duplex color-flow sonography measures
      noninvasively the third and the lateral ventricle in adults.

PMID- 7718937
TI  - Ophthalmoplegia and facial numbness following treated squamous carcinoma of the
      forehead.
AB  - A 62-year-old man presented with progressive diplopia, left ptosis, proptosis,
      complete ophthalmoplegia, facial numbness, and headache of 2 1/2 months'
      duration. The symptoms started 1 month after surgical resection of a squamous
      cell carcinoma in the left side of the forehead. Imaging studies helped localize
      the lesion, correlating with clinical features. The differential diagnosis is
      discussed. The final diagnosis was confirmed by autopsy.

PMID- 7718938
TI  - Peak velocity overestimation and linear-array spectral Doppler.
AB  - Ultrasound instruments are used to evaluate blood flow velocities in the human
      body. Most clinical instruments perform velocity calculations based on the
      Doppler principle and measure the frequency shift of a reflected ultrasound beam.
      Doppler-only instruments use single-frequency, single-crystal transducers. Linear
      and annular-array multiple-crystal transducers are used for duplex scanning
      (simultaneous B-mode image and Doppler). Clinical interpretation relies primarily
      on determination of peak velocities or frequency shifts as identified by the
      Doppler spectrum. Understanding of the validity of these measurements is
      important for instruments in clinical use. The present study examined the
      accuracy with which several ultrasound instruments could estimate velocities
      based on the identification of the peak of the Doppler spectrum, across a range
      of different angles of insonation, on a Doppler string phantom. The string was
      running in a water tank at constant speeds of 50, 100, and 150 cm/sec and also in
      a sine wave pattern at 100- or 150-cm/sec amplitude. Angles of insonation were
      30, 45, 60, and 70 degrees. The single-frequency, single-crystal transducers (PC
      Dop 842, 2-MHz pulsed-wave, 4-MHz continuous-wave) provided acceptably accurate
      velocity estimates at all tested velocities independent of the angle of
      insonation. All duplex Doppler instruments with linear-array transducers (Philips
      P700, 5.0-MHz; Hewlett-Packard Sonos 1000, 7.5-MHz; ATL Ultramark 9 HDI, 7.5-MHz)
      exhibited a consistent overestimation of the true flow velocity due to increasing
      intrinsic spectral broadening with increasing angle of insonation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7718939
TI  - Magnetic resonance evidence of perineural metastasis.
AB  - Contiguous spread along perineural and endoneural spaces, that is, perineural
      tumor extension, in cutaneous squamous cell carcinoma is fairly common.
      Infrequently, these tumors spread and involve intracranial structures. One
      consequence of this complication is meningeal carcinomatosis which is
      underrecognized. Herein described is a patient with recurrent cutaneous squamous
      cell carcinoma with perineural invasion along the maxillary nerve that was
      subsequently shown by magnetic resonance imaging to the trigeminal root. The
      patient initially presented with a cavernous sinus syndrome but despite
      aggressive treatment, extensive meningeal carcinomatosis and cauda equina
      dysfunction developed. Awareness of perineural invasion and proper evaluation are
      crucial. Perineural spread intracranially worsens the prognosis and limits
      treatment options to palliation.

PMID- 7718940
TI  - Progressive multifocal leukoencephalopathy presenting as multiple enhancing
      lesions on MRI: case report and literature review.
AB  - This report describes an immunocompetent patient with memory loss and motor
      abnormalities whose magnetic resonance images demonstrated multiple enhancing
      white matter lesions, including one that was cystic, suggestive of metastatic
      tumors or abscesses. Neuropathological evaluation at biopsy and subsequent
      autopsy revealed progressive multifocal leukoencephalopathy. Magnetic resonance
      evidence of enhancement and cystic changes are rare findings in progressive
      multifocal leukoencephalopathy, but should be considered in the differential
      diagnosis, especially in patients without evidence for primary malignancy or
      infection.

PMID- 7718941
TI  - Epidural mass related to calvarial aneurysmal bone cyst: computed tomographic and
      magnetic resonance demonstration.
AB  - The computed tomographic and magnetic resonance appearance of a calvarial
      aneurysmal bone cyst is described. Both forms of imaging demonstrate an epidural
      mass in the right occiput. The fluid-fluid levels in the mass on the T2-weighted
      images are characteristic of, though not specific for, aneurysmal bone cyst.

PMID- 7718942
TI  - Lumbosacral spinal intradural extramedullary paciniomyolipoma: magnetic resonance
      imaging, computed tomography, and pathology findings.
AB  - This report describes a paciniomyolipoma as an intradural tumor of the lumbar
      spinal cord composed of adipose tissue, striated skeletal muscle, and pacinian
      corpuscles. Simple lipomas, myolipomas, and other variant lipomas of the spinal
      cord have been described in the literature; to the authors' knowledge, however,
      this is the first report of this unusual and unique lipoma.

PMID- 7718943
TI  - Brain metastases from primary lung malignant fibrous histiocytoma: a case report.
AB  - Primary malignant fibrous histiocytomas are rare. The authors report on a 56-year
      old man who presented with neurological symptoms due to cerebral metastasis of a
      primary malignant fibrous histiocytoma of the lung.

PMID- 7718944
TI  - Doppler monitoring of middle cerebral artery emboli from carotid stenoses.
AB  - The aim of this study was to prove the existence of clinically silent
      embolization arising from carotid stenoses. Simultaneous bilateral transcranial
      Doppler sonography of the middle cerebral artery was carried out during 10
      minutes in 30 patients having ultrasonically demonstrated unilateral (n = 12) or
      bilateral internal carotid stenoses (n = 18). Twenty-four of the stenoses were
      clinically considered to be symptomatic and 24 were asymptomatic. Emboli signals
      were detected in 5 of the 30 patients. All occurred unilaterally on the side of a
      high-grade carotid stenosis. Four of the 5 lesions were symptomatic, and 1 was
      asymptomatic.

PMID- 7718945
TI  - Noninvasive assessment of intracranial perfusion in acute cerebral ischemia.
AB  - Single-photon emission computed tomography (SPECT) and transcranial Doppler
      sonography (TCD) may help to determine a target group of patients with maximum
      therapeutic response for tissue rescue after acute stroke. As previously
      described, the cerebral perfusion index represents a combination of these
      techniques, and is calculated by multiplying assigned values for TCD and SPECT
      perfusion patterns. The three grades of cerebral perfusion index (1-5, 6-12, 15
      20) may predict short-term outcome if the index is based on SPECT and TCD
      performed within the first 6 hours after stroke. A total of 30 consecutive
      patients were studied (18 with middle cerebral artery stroke and 12 with
      transient ischemic attack or minor stroke). Neurological deficit was scored using
      the Canadian Neurological Scale. SPECT and TCD were performed 4 +/- 2 hours after
      the onset. Forty-five minutes were required to perform both tests, evaluate the
      results, and calculate the cerebral perfusion index. The mean score (+/- standard
      deviation) of the neurological deficit on admission was 84 +/- 20 in patients
      with transient ischemic attack/minor stroke and 54 +/- 33 in patients with stroke
      (p < 0.009). The volume of ischemic lesion was measured on computed tomography
      scans performed more than 3 days after the ictus. Patients with transient
      ischemic attack/minor stroke had lesion volumes of 8 +/- 7 cm3 compared to 72 +/-
      26 cm3 for those with stroke (p < 0.0001). The mean cerebral perfusion index in
      the transient ischemic attack group was 18 +/- 4, while in the stroke group it
      was 4 +/- 1 (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7718946
TI  - Gray-to-white matter ratios of HMPAO in the human brain.
AB  - The gray-to-white matter ratio of technetium 99m-hexamethylpropyleneamine oxime
      (99mTc-HMPAO) in 14 anesthetized patients undergoing partial brain resection for
      treatment of complex partial seizures. The gray-to-white matter ratio of 99mTc
      HMPAO was 1.8:1 (standard deviation 0.6) in the temporal lobe. Many of the
      biopsied specimens demonstrated histopathological abnormalities.

PMID- 7718947
TI  - Transcranial color-coded real-time sonography of intracranial veins. Normal
      values of blood flow velocities and findings in superior sagittal sinus
      thrombosis.
AB  - Sonographic findings in patients with superior sagittal sinus thrombosis were
      compared to those in healthy adults. Two patients with angiographically verified
      superior sagittal sinus thrombosis were examined by transcranial color-coded real
      time sonography (TCCS) after intravenous application of a pulmonary stable
      ultrasound contrast agent. For comparison, 10 patients without venous pathology
      had contrast-enhanced TCCS; in addition, 30 healthy adults had plain TCCS to
      determine the identification rate for deep and superficial venous segments and to
      define normal values of venous blood flow velocities. The straight sinus was
      identified in 22 of 30 healthy subjects by plain TCCS, and in 9 of 10 patients by
      contrast-enhanced TCCS. The mean peak and angle-corrected blood flow velocity was
      19.1 +/- 7.1 cm/sec. The superior and inferior sagittal sinuses were identified
      by contrast-enhanced TCCS in 2 and 1 subjects, respectively; they were never seen
      on plain TCCS. In the 2 patients with sagittal sinus thrombosis a distinct
      increase of blood flow velocity was recorded from the straight sinus (83 and 92
      cm/sec), most likely reflecting collateral circulation. These preliminary data
      indicate that TCCS and particularly contrast-enhanced TCCS permit identification
      and blood flow measurements within the deep and occasionally, the superficial
      venous system. TCCS may contribute to an assessment of hemodynamic repercussions
      of venous thrombosis and may indicate the risk of venous infarction and
      hemorrhage.

PMID- 7718948
TI  - Hippocampal volume measurements using magnetic resonance imaging in normal young
      adults.
AB  - Volumetric analysis of brain magnetic resonance images (MRIs) measures structural
      changes associated with neurological and neuropsychiatric disorders. Several
      studies investigated the hippocampus specifically, reporting degrees of atrophy
      in such disorders. However, the range of normal hippocampal volumes must be known
      to assess atrophy. In tracings of T1 oblique slice and three-dimensional MRIs in
      24 normal subjects reported here, the average volume of right and left
      hippocampus was 2.90 cm3 and 2.78 cm3, respectively. On paired analysis, this
      difference was significant. The literature indicated these volumes are in the
      middle of a wide range of hippocampal volumes (1.73-5.68 cm3) in both MRI-based
      and histology-based studies. This wide variation can be explained by differing
      hippocampal boundary definitions; technical factors of image processing,
      segmentation, and display; sample heterogeneity; and interoperator differences.

PMID- 7718949
TI  - [Adjuvant treatments of breast cancer].

PMID- 7718950
TI  - [Hormonal therapy of breast cancer].

PMID- 7718951
TI  - [New hormonal therapies].

PMID- 7718952
TI  - Circadian variations and prednisolone-induced alterations of circulating
      lymphocyte subsets in man.
AB  - We determined the circadian variations and prednisolone (PSL)-induced alterations
      of circulating lymphocyte subsets in 10 healthy adults by two-color flow
      cytometry using monoclonal antibodies to various lymphocyte subsets in order to
      collect fundamental data for monitoring of the subsets in clinical practice. This
      study first examined the changes of CD5+ B cells, gamma delta+ or gamma delta-T
      cells, activated (HLA-DR+) CD4+ or CD8+ cells, CD11b+ or CD11b-CD8+ cells, and
      natural killer (NK) cell subsets (CD16+CD57-, CD16+CD57+, CD16-CD57+), in
      addition to other subsets described before. Compared with the base line values
      obtained at 9:00 (AM) on day 1, lymphocytes, total B cells, CD5+ B cells, total T
      cells, gamma delta-T cells, CD4+ cells, activated CD4+ cells, CD45RA-CD4+ cells,
      and activated CD8+ cells were significantly increased at 20:00 (PM). However, the
      numbers of CD45RA+CD4+ cells, CD11b+ or CD11b-CD8+ cells and three NK cells
      subsets did not show significant circadian variations. After oral PSL (30 mg),
      which was given at 7:00 (AM) on day 2, lymphocytes and almost all lymphocyte
      subsets, except for CD16+CD57- cells, were significantly decreased; these changes
      recovered between 13 and 26 hours after PSL administration. The circadian
      variations and PSL-induced alterations of lymphocyte subsets were relatively
      comparable, but PSL administration cause a decrease in a wider range of
      lymphocyte subsets including relatively corticosteroid-resistant subsets such as
      CD45RA+CD4+ cells, CD8+ cell and NK cell subsets.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7718953
TI  - Impaired interleukin-2 production in active ulcerative colitis is reversed by
      calcium ionophore plus phorbol myristate acetate and related to altered
      intracellular Ca2+ responses.
AB  - Phytohemagglutin in (PHA)-induced IL-2 production in vitro by peripheral blood
      mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) from
      patients with active UC (n = 24, n = 8, respectively) was significantly less than
      that in controls (n = 13, n = 8, respectively) and inactive patients (n = 11). In
      contrast, PBMC from inactive disease showed no significant difference when
      compared with the controls. Depressed IL-2 production in active UC was not
      reversed by the addition of anti-CD3 monoclonal antibody plus phorbol myristate
      acetate (PMA), but was largely reversed by adding calcium ionophore plus PMA.
      Using a fluorescent Ca2+ probe fura-2, we found that after PHA stimulation LPMC
      from patients with active UC showed a lower magnitude of rise in intracellular
      free calcium concentration ([Ca2+]i) than control cells. These results suggest
      that impaired PHA-induced IL-2 production in active UC may be related to some
      alterations of the early signaling events that cause elevation of the [Ca2+]i.

PMID- 7718954
TI  - The effects of chronic endoscopic variceal sclerotherapy on systemic and
      splanchnic hemodynamics in patients with cirrhosis.
AB  - The aim of this study was to determine whether endoscopic variceal sclerotherapy
      affects systemic or splanchnic hemodynamics. We measured hemodynamic parameters
      before and after the first course of sclerotherapy in 35 patients with cirrhosis.
      Following sclerotherapy, there was a significant decrease in cardiac index and a
      significant increase in systemic vascular resistance. Changes in hepatic venous
      pressure gradient varied from patient to patient with no statistically
      significant change in the group overall. However, all 20 patients with a decline
      in the hepatic venous pressure gradient had a concomitant decrease in cardiac
      index and/or a large extravariceal shunt. The multivariate analysis disclosed
      that the decrease in cardiac index was a statistically significant contributor
      for the decline in hepatic venous pressure gradient. We conclude that the
      obliteration of esophageal varices by sclerotherapy significantly reverses the
      hyperdynamic circulatory state in patients with cirrhosis. Spontaneous changes in
      systemic hemodynamics and the interaction with hepatic hemodynamics must be taken
      into account when evaluating hepatic hemodynamics in patients undergoing variceal
      sclerotherapy.

PMID- 7718955
TI  - A congenital variant of thrombotic thrombocytopenic purpura in two siblings.
AB  - We describe two siblings affected by chronic relapsing thrombotic
      thrombocytopenic purpura from infancy. The elder brother, a 12-year-old boy had
      50 such episodes characterized by acute onset of fever, headache, drowsiness,
      vomiting, dark urine, thrombocytopenia and anemia. The younger sister, a 6-year
      old girl, had 8 episodes with the same clinical manifestations. Petechiae and
      ecchymoses on the extremities were present throughout their lives. Furthermore,
      anemia with evidence of red blood cell fragmentation and thrombocytopenia were
      present chronically. Periodical transfusion of frozen fresh plasma prevented
      recurrent episodes. These cases suggest that there is a congenital variant of
      thrombotic thrombocytopenic purpura.

PMID- 7718956
TI  - Takayasu's disease associated with ulcerative colitis.
AB  - A 14-year-old female with ulcerative colitis developed right anterior cervical
      pain and high fever. Cervical contrast-enhanced computed tomography (CE-CT)
      showed a wall thickness of the right common carotid artery which suggested
      aortitis. Her pulmonary angiography demonstrated a narrowing of the pulmonary
      arteries and she was diagnosed as having Takayasu's disease associated with
      ulcerative colitis. HLA analysis showed Bw52 and DR2 haplotype, which is
      frequently found in patients with Takayasu's disease associated with ulcerative
      colitis.

PMID- 7718957
TI  - Amyloidosis secondary to rheumatoid arthritis associated with plexiform change in
      bilateral temporal lobes.
AB  - A 70-year-old woman with rheumatoid arthritis (RA) and secondary amyloidosis
      presented repeated consciousness loss. The pathological findings at autopsy
      revealed multi-organic deposits of amyloid A-protein and so-called 'plexiform
      change' of blood vessels in bilateral temporal lobes. The arterial plexiform
      change, which is found in the lung specimen of primary pulmonary hypertension,
      might be a new pathological cerebrovascular change associated with RA.

PMID- 7718958
TI  - Pulmonary hypertension and antiphospholipid antibody in a patient with Sjogren's
      syndrome.
AB  - A 57-year-old female patient with Sjogren's syndrome was complicated with
      pulmonary hypertension (PH) and antiphospholipid antibody (aPL). She had a
      history of fetal losses, deep vein thrombosis and chronic thyroiditis. On
      admission, severe pulmonary hypertension, thrombocytopenia, lupus anticoagulant
      and a decreased level of protein C were found. Pulmonary artery perfusion
      scintigram revealed multiple defects. She died suddenly despite an intensive
      therapy. Intimal proliferation with angiomatoid lesions in small pulmonary
      arteries was observed by autopsy. Since a close relationship between PH and aPL
      in connective tissue disease is found, it is important to carefully analyze the
      antiphospholipid antibodies in patients with PH.

PMID- 7718959
TI  - Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and Gerhardt
      syndrome associated with Shy-Drager syndrome.
AB  - This is the first report on a case of syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH) associated with Gerhardt syndrome (paralysis of
      bilateral vocal cords). A 67-year-old Japanese man suffering from progressive
      autonomic failure was diagnosed as having Shy-Drager syndrome (SDS) with
      hyponatremia due to SIADH and severe sleep apnea caused by a bilateral recurrent
      nerve palsy. Water load test showed alteration in diuresis which was corrected by
      phenytoin. Arginine vasopressin secretion was not suppressed by plasma osmolality
      below 280 mOsm/kgH2O. Impairment of the afferent pathways of baroreceptors, or
      impairment of the osmoreceptors could be speculated as the etiological factor of
      the SIADH observed in this case.

PMID- 7718960
TI  - Popliteal venous aneurysm with pulmonary embolism.
AB  - A 29-year-old female was admitted to the hospital because of increasing
      exertional dyspnea, chest oppressive feeling and palpitation. Lung perfusion
      scan, pulmonary angiography, and venography of the lower extremities revealed
      multiple pulmonary embolism and a right popliteal venous aneurysm as the probable
      source of emboli. B-mode/Doppler echography and magnetic resonance imaging were
      useful for the preoperative evaluation. Following anticoagulant therapy and
      thrombolytic therapy using intravenous heparin and urokinase, respectively, the
      popliteal venous aneurysm was surgically excised; the walls contained organized
      thrombus. She delivered a baby without any complication 2 years after the
      surgery.

PMID- 7718961
TI  - Peripheral neuroectodermal tumor presenting pleural effusion.
AB  - Pleural effusion is a common finding of peripheral neuroectodermal tumor (PNET)
      of the chest wall (Askin's tumor), but little is known about the characteristics.
      A case of Askin's tumor with pleural effusion is reported. Repeated cytologies
      were negative for malignancy, but levels of lactic dehydrogenase (LDH) and neuron
      specific enolase (NSE) in the pleural effusion were increased. Surgical biopsy
      was performed and immunohistochemical study of the tumor revealed the diagnosis.

PMID- 7718962
TI  - Characterization of immunoglobulin heavy chain gene rearrangements in chronic
      myeloid leukemia with recurrent B-lymphoid blast crisis following bone marrow
      transplantation.
AB  - We sequentially analyzed the immunoglobulin heavy chain (IgH) variable region
      gene of leukemia cells obtained from a chronic myeloid leukemia (CML) patient who
      had three episodes of B-lymphoid crisis after bone marrow transplantation.
      Southern blots using the JH probe showed a single rearranged band which differed
      at each crisis, although the rearranged bands of the BCR gene were the same at
      each crisis. The IgH variable region sequences of the leukemia cells at each
      crisis were different. These observations suggested that multiple clones were
      generated from the progenitor cells of the blast crisis, which were transformed
      at a very early stage of B-lymphocyte ontogeny.

PMID- 7718963
TI  - Adrenogenital syndrome caused by an androgen-producing adrenocortical tumor.
AB  - We describe here a typical case of virilizing adrenocortical tumor. A 23-year-old
      Japanese woman had her male-like musculature, hirsutism, the absence of breast
      development and marked clitoromegaly. Adrenal androgens were remarkably elevated,
      with plasma dehydroepiandrosterone sulfate 2,752 micrograms/dl, plasma
      testosterone 250 ng/dl and urinary 17-ketosteroids 203.4 mg/day. A well
      encapsulated tumor approximately 7 cm in diameter was detected in the left
      adrenal gland by computed tomography, magnetic resonance imaging and
      arteriography. The tumor was surgically resected and histologically diagnosed as
      a benign adrenocortical adenoma. The elevated adrenal androgens returned to
      normal postoperatively with amelioration of her masculinized clinical features.

PMID- 7718964
TI  - Rare case with metastatic involvement of hypothalamo-pituitary and pineal body
      presenting as hypopituitarism and diabetes insipidus.
AB  - An unusual case with metastatic spread of a small oat cell lung carcinoma to the
      hypothalamo-pituitary region and pineal body presenting as pituitary
      insufficiency is reported. Computed tomographic scan revealed an isodense mass in
      the hypothalamo-pituitary region and pineal body that was strongly enhanced by
      contrast medium. Magnetic resonance imaging demonstrated a downward displacement
      of the posterior lobe of the pituitary by the hypothalamo-pituitary mass. Dynamic
      assessment of hypothalamo-pituitary function showed hypopituitarism and diabetes
      insipidus; partial recovery was observed with the improvement in the carcinoma by
      chemotherapy. The brain was subsequently irradiated. The patient survived 10
      months.

PMID- 7718965
TI  - Guillain-Barre syndrome following fulminant viral hepatitis A.
AB  - Guillain-Barre syndrome (GBS) developed soon after the onset of acute viral
      hepatitis A (HA) in a 62-year-old man. GBS associated with HA is extremely rare,
      even though HA is common. In a review of case reports the clinical features of
      GBS following HA could be summarized as follows: 1) Most of the patients are men.
      2) GBS develops within 14 days after the onset of HA. 3) Facial nerve palsy is
      frequently present. 4) Proprioception is likely impaired in addition to
      superficial sensation. 5) The outcome of neuropathic symptoms is uniformly good,
      regardless of the degree of liver dysfunction as evaluated on the basis of
      alanine aminotransferase levels. These findings indicate that GBS following HA
      essentially does not differ from typical GBS.

PMID- 7718966
TI  - Erythropoietic protoporphyria with severe cholestasis.
AB  - A 74-year-old woman with erythropoietic protoporphyria (EPP) with hepatic
      dysfunction is reported. She had been photosensitive for two years prior to
      admission. Physical examination revealed hepatosplenomegaly and erosions on her
      face. Moderate increases in serum bilirubin and biliary tract enzymes were noted.
      Histology of the biopsied liver revealed moderate fibrosis and dilatation of bile
      canaliculi containing orange pigment. Marked increases in protoporphyrin in
      erythrocytes and feces were noted. The patient died of hepatic failure a year and
      a half after admission with maximum serum bilirubin of 34 mg/dl. This patient
      seems to be the oldest among reported EPP cases with liver dysfunction.

PMID- 7718967
TI  - The first case of polymyositis associated with interferon therapy.
AB  - A 54-year-old man with renal cell carcinoma was treated with interferon (IFN)
      gamma for 3 weeks soon after nephrectomy. Three months later he received IFN
      alpha therapy for 8 weeks due to chronic active hepatitis C. He subsequently
      contracted polymyositis (PM): proximal muscle weakness, an elevation of muscle
      enzymes, myogenic patterns on the electromyograph and histologically specific
      findings in biopsied muscle specimens. After discontinuation of IFN his muscular
      weakness gradually recovered.

PMID- 7718968
TI  - Cutaneous vasculitis in a patient with dermatomyositis without muscle
      involvement.
AB  - A 74-year-old female patient with cutaneous ulcerations and typical
      dermatomyositis (DM) skin rash had no muscle disease for a 1-year and 5 months
      period. Histological examination of the skin ulceration indicated vascular
      occlusion without cellular infiltration. Cutaneous ulceration is a very rare
      manifestation of adult-onset DM patients without inflammatory myopathy.

PMID- 7718969
TI  - Insulinoma with normal plasma insulin concentrations and insulin/glucose ratios
      during hypoglycemic episodes.
AB  - A patient with insulinoma had frequent hypoglycemic episodes with normal plasma
      insulin levels and insulin/glucose ratios. When immunoreactive insulin (IRI)
      concentrations in this patient were compared among plasma samples with the same C
      peptide immunoreactivity (CPR) levels, the concentrations were significantly
      lower than in control patients with insulinoma and equal to or lower than those
      of normal subjects. In hepatic venous samples, CPR levels were significantly
      higher and the IRI/CPR molar ratios were lower than those in a control subject.
      These results may indicate that normoinsulinemia in this patient could be
      explained by increased hepatic extraction of insulin.

PMID- 7718970
TI  - Massive pericardial effusion in a patient with Hashimoto's thyroiditis:
      histological examination of underlying cardiomyopathy.
AB  - An unusual case of a hypothyroid patient with huge pericardial effusion due to
      Hashimoto's thyroiditis is reported. Cardiac tamponade occurred during admission.
      Eight hundred milliliters of pericardial effusion was withdrawn by
      pericardiocentesis. Even after successful replacement of thyroid hormone, she had
      recurrent effusion two years later. Refractory pericardial effusion is a rare
      complication in treated hypothyroid patients. Underlying cardiomyopathy was
      presented with hemodynamic and histological examinations.

PMID- 7718971
TI  - Recurrent Cushing's disease associated with nephrotic syndrome.
AB  - A case of recurrent Cushing's disease with nephrotic syndrome due to
      membranoproliferative glomerulonephritis (MPGN) is presented. Functional
      pituitary adenoma recurred 6 years after transsphenoidal pituitary adenomectomy.
      Due to infiltration into the surrounding tissues, transcranial surgery was
      performed. However, this failed to induce a remission and thus gamma knife
      therapy was applied. Histopathological evaluation revealed that the glomerular
      lesions had progressed to a rather advanced stage of MPGN. Although this
      association could be coincidental, the recurrence of pituitary macroadenoma might
      be induced by the cessation of steroid treatment for the nephrotic syndrome.

PMID- 7718972
TI  - Chronic lymphocytic leukemia associated with nephrotic syndrome and
      dermatomyositis.
AB  - Several types of autoimmune complications of chronic lymphocytic leukemia (CLL)
      have been previously reported. However, the tendency to develop autoantibodies is
      usually restricted to the hematopoietic system. We report a 68-year-old man who
      had developed dermatomyositis after ten years of chemotherapy for CLL. He also
      had secondary nephrotic syndrome at the onset of CLL. Subsequently, the patient
      died of perforation of the small intestine. The association of both nephrotic
      syndrome and dermatomyositis with CLL is very rare. We discuss the possibility of
      a casual relation.

PMID- 7718973
TI  - Boucher-Neuhauser syndrome associated with hypocalciuric hypercalcemia.
AB  - A 52-year-old woman was diagnosed as having cerebellar ataxia, hypogonadotropic
      hypogonadism and retinochoroidal degeneration, the so-called, "Boucher-Neuhauser"
      syndrome proposed by Limber et al (Am J Med Genet 33:409, 1989). In addition,
      laboratory findings showed the elevation of serum calcium (Ca) levels, low
      urinary Ca excretion, and exaggerated reabsorption of filtrated Ca (FECa:0.14%),
      suggesting complication of hypocalciuric hypercalcemia. This is a very rare case
      of Boucher-Neuhauser syndrome associated with hypocalciuric hypercalcemia.

PMID- 7718974
TI  - Thrombotic thrombocytopenic purpura and myoglobinuric acute renal failure
      following radiation therapy in a patient with polymyositis and cervical cancer.
AB  - A 73-year-old woman was admitted to receive radiation treatment for uterine
      cervical cancer, however a complex series of events ensued, leading to death. She
      developed an acute exacerbation of polymyositis complicated by thrombotic
      thrombocytopenic purpura, rhabdomyolysis and acute renal failure. Radiation
      therapy may have produced an immune disturbance leading to the acute exacerbation
      of polymyositis. Auto-immune-mediated endothelial damage might have triggered a
      series of events leading to thrombotic thrombocytopenic purpura. Rhabdomyolysis
      seemed to be the main cause of acute renal failure.

PMID- 7718975
TI  - Refractory anemia with an excess of blasts developed into overt leukemia with
      leukothrombocytosis.
AB  - A 72-year-old man with refractory anemia with an excess of blasts developed overt
      leukemia with leukothrombocytosis. Hematological and physical findings closely
      resembled those of an accelerated or blastic phase of chronic myelocytic
      leukemia. The cytogenetic anomaly of i(17q) was observed during the course. The
      present case is suggestive of the diversities of myelodysplastic syndromes (MDS),
      including relationships between MDS and myeloproliferative disorders (MPD) and
      acute leukemia.

PMID- 7718976
TI  - Plasmodium vivax malaria infection diagnosed by indirect fluorescent antibody
      test.
AB  - We present the diagnostically challenging case of a 51-year-old Japanese male who
      visited Papua New Guinea for one month. Approximately a month after returning to
      Japan, he experienced a high fever. Malaria was suspected and he was admitted to
      Tsukuba University Hospital. Although the blood smear did not reveal the malarial
      parasite, a diagnosis of malaria was made using an indirect fluorescent antibody
      test (IFAT). The patient was treated and discharged but symptoms returned three
      months later. This time, the blood smear was positive for malarial parasites.
      IFAT was useful in this case for the early diagnosis of Plasmodium vivax and for
      ruling out infection by Plasmodium falciparum.

PMID- 7718977
TI  - B-cell lymphoma terminating in acute monoblastic leukemia.
AB  - A case of CD11b-, CD14- and CD36-positive B-cell lymphoma terminating in acute
      monoblastic leukemia is presented. The patient was initially suspected as having
      angiotrophic lymphoma due to proliferation of lymphoma cells within the sinusoid
      of the liver and clinical signs. Following chemotherapy, the lymphoma cells were
      converted into CD11b- and CD36-positive monoblasts. Lineage switching of B-cell
      lymphoma to acute monoblastic leukemia may have occurred in this case.

PMID- 7718979
TI  - Septic pulmonary emboli secondary to pyogenic liver abscess in a diabetic
      patient.
AB  - A 70-year-old woman with poorly controlled diabetes mellitus was admitted because
      of persistent remittent fever. Soon a liver abscess was detected as the cause of
      the fever by ultrasonography, and antibiotic therapy was started. However,
      suddenly serious dyspnea with chest and back pain developed. The morbid condition
      was definitely diagnosed as septic pulmonary emboli (SPE) with pulmonary
      perfusion scan. It should be recognized that liver abscess can be a latent focus
      of systemic metastatic complications such as SPE, and not only early detection
      but also prompt appropriate drainage of liver abscesses is essential.

PMID- 7718980
TI  - Nephrotic syndrome associated with fibrillary deposits in the glomeruli.
AB  - A 48-year-old woman with nephrotic syndrome underwent renal biopsy. Light
      microscopy showed nodular sclerosis and thickening of the glomerular capillary
      wall. Immunoglobulins (Ig) G, especially IgG2, IgM, IgA, C3, C1q were detected
      along the glomerular capillary walls by immunofluorescent microscopy. Electron
      microscopy revealed that fibrillar materials of about 25 nm were accumulated in
      the subepithelial area of the glomerular basement membrane. These materials were
      negative for Congo-red staining. Neither cryoglobulinemia nor paraproteinemia
      including light chains was found. This case was diagnosed as membranous
      nephropathy by clinical findings and pathological examinations, and seemed to be
      a case of fibrillary glomerulonephritis.

PMID- 7718978
TI  - Rectus hematoma secondary to vomiting: a complication of conditioning regimen for
      bone marrow transplantation.
AB  - A 41-year-old woman with chronic myelogenic leukemia was scheduled to undergo
      transplantation of bone marrow. The patient complained of nausea and vomiting
      following the initiation of chemotherapy. One day prior to the planned
      termination of chemotherapy, the patient developed left-sided abdominal pain.
      Physical examination and imaging examination indicated the possibility of acute
      abdomen associated with bleeding or herniation. For therapeutic and diagnostic
      purposes, an emergency operation was performed. A 6 x 5 cm hematoma was detected
      within the left rectus abdominis muscle. It is suggested that the
      gastrointestinal symptoms should be carefully controlled in patients undergoing
      bone marrow transplantation.

PMID- 7718981
TI  - Postcholecystectomy syndrome mimicking angina pectoris detected by the morphine
      provocation test.
AB  - A 66-year old woman had had intermittent anterior chest pain and upper abdominal
      pain for 15 years. Angina pectoris was diagnosed at the age of 51 years, as she
      had typical anginal pain that was relieved by nitroglycerine, although coronary
      arteriography was normal and the ergonovine provocative test was negative. She
      had undergone cholecystectomy at the age of 38 years. Her bile duct pressure
      increased markedly after morphine injection and severe pain with the
      aforementioned distribution was produced. Postcholecystectomy syndrome due to
      sphincter of Oddi spasm was diagnosed and her pain was relieved by endoscopic
      sphincterotomy.

PMID- 7718982
TI  - Detection of Cryptococcus neoformans in bronchial lavage cytology: report of four
      cases.
AB  - Four cases of pulmonary cryptococcosis were diagnosed by cytological detection of
      Cryptococcus neoformans in bronchial lavage. Three patients had underlying
      diseases, but not HIV infection. The chest X-rays showed 2 patients with nodular
      lesions and 2 with cavitary lesions. The cryptococcal antigen in the serum was
      positive in all four patients. In the cytology of bronchial lavage, Cryptococcus
      neoformans was detected after period-acid-Schiff (PAS) staining and was cultured
      in Sabouraud-dextrose agar. The cytology of bronchial lavage is useful for the
      rapid diagnosis of pulmonary cryptococcosis.

PMID- 7718983
TI  - Graves' hyperthyroidism following transient thyrotoxicosis during interferon
      therapy for chronic hepatitis type C.
AB  - We report a case of Graves' hyperthyroidism induced by long-term interferon (IFN)
      therapy. A 52-year-old woman suffered from chronic active hepatitis type C and
      was treated with a total of 456 x 10(6) units of IFN-alpha for 23 weeks. During
      the 12th week of treatment she showed transient thyrotoxicosis. One week after
      the termination of IFN therapy, TSH-receptor antibodies became positive and
      subsequently she showed Graves' hyperthyroidism. This case showed sequential
      manifestation from transient thyrotoxicosis to the appearance of TSH-receptor
      autoantibodies, and then the occurrence of Graves' hyperthyroidism during IFN
      therapy. The course of this case may be useful in the understanding of the
      pathogenesis of autoimmune hyperthyroidism.

PMID- 7718984
TI  - CRST syndrome (calcinosis cutis, Raynaud's phenomenon, sclerodactyly, and
      telangiectasia) associated with autoimmune hepatitis.
AB  - A case of Raynaud's phenomenon, was complicated with autoimmune hepatitis (AIH)
      during the clinical course, and subsequently with gangrene of the fingertips
      caused by CRST syndrome (calcinosis cutis, Raynaud's phenomenon, sclerodactyly
      and telangiectasia). The presence of anticentromere antibodies is rare in AIH; to
      date, there has been only one report of a combination of AIH and CRST syndrome.
      This combination of the two diseases has been identified only in Japan.

PMID- 7718985
TI  - Squamous cell carcinoma of the pancreas with massive invasion of the
      retroperitoneum.
AB  - A 79-year-old woman with a rare form of pancreatic carcinoma with massive
      invasion of the retroperitoneum presented with upper abdominal pain and vomiting.
      Although examination (computed tomography, barium enema, upper gastrointestinal
      series) suggested peritonitis carcinomatosa due to pancreatic cancer, a primary
      lesion of the pancreas was not confirmed by endoscopic retrograde
      pancreatography. Autopsy ultimately revealed a small tumor (5 x 8 mm) of the
      uncinate process of the pancreas near the duodenum with peritonitis
      carcinomatosa. Microscopically, the tumor and its metastasis consisted of poorly
      differentiated squamous cell carcinoma without adenocarcinomatous change, a rare
      form of pancreatic tumor.

PMID- 7718986
TI  - IL-5 predominant in bronchoalveolar lavage fluid and peripheral blood in a
      patient with acute eosinophilic pneumonia.
AB  - We describe an acute eosinophilic pneumonia (AEP) patient with bronchoalveolar
      lavage fluid (BALF). Eosinophil cell number (47%), content of interleukin (IL)-5
      (8.22 x 10(2) pg/ml) and eosinophil cationic protein (9.25 micrograms/ml) were
      high in BALF. No eosinophilia was seen in peripheral blood on admission; however,
      content of IL-5 was 9.47 x 10(2) pg/ml. After methylprednisolone pulse therapy,
      he improved rapidly with a reduction in eosinophil cell number (7%) and the
      content of IL-5 (< 100 pg/ml) in BALF. However, a high content of IL-5 (6.9 x
      10(2) pg/ml) and transient eosinophilia (17.5%) were seen in peripheral blood. It
      is important to distinguish between AEP and infectious pneumonia, because of the
      differing treatments. If the diagnosis of AEP is doubtful, BALF should be
      performed early.

PMID- 7718987
TI  - Liver damage after danazol and glucocorticoids for chronic idiopathic
      thrombocytopenic purpura (ITP)

PMID- 7718988
TI  - 'The nurse acting as surgeon's assistant'.

PMID- 7718990
TI  - NATN library: how to utilise this resource.

PMID- 7718989
TI  - Peri-operative deaths of children.
AB  - A recent report of the National Confidential Enquiry into Peri-operative Deaths
      in children under the age of ten, looked to the problems of surgery and
      anaesthesia. The enquiry revealed that there must be changes in surgical practice
      since children need special skills and facilities, and to ensure that surgeons
      and anaesthetists do not undertake occasional paediatric experience. They advise
      that no trainee should undertake any anaesthetic or surgical operation on a child
      of any age without the express permission of his or her consultant. Some
      disagree, saying that the overall standard of surgical and anaesthetic care of
      children is excellent, nevertheless, they do feel there is some room for
      improvement. The main deficiencies were failure to supervise junior staff,
      consultants not seeing patients before operations and general surgeons performing
      operations that should have been done by specialists. Surgeons used to be able to
      bury their mistakes. This is no longer the case because of the increasing number
      of reports which closely examine surgical deaths.

PMID- 7718992
TI  - A personal perspective of quality and audit within the NHS.

PMID- 7718991
TI  - Designing a common core curriculum for operating department nursing.
AB  - This paper has been written to outline the experiences of the European Operating
      Room Nurses Association in designing a Common Core Curriculum for European
      Operating Room Nursing. The process of curriculum planning is never one to be
      undertaken without an understanding of the complexity of producing what often
      appears as nothing more than a simple document once the task is completed. In
      most situations the planning of a curriculum is undertaken by a small team of
      people who prepare a structure and content which they themselves are actually
      going to implement, therefore the curriculum responds to the needs of the
      particular location for which it is intended. When a National Curriculum is
      developed it is usually done so by a group of people who work within the
      framework and guidelines of a national body, but they include local
      representatives from different areas to ensure that the finished product is one
      which can usefully be applied to all areas of the country. The designing of a
      curriculum for Europe brings a whole new dimension to curriculum planning.

PMID- 7718993
TI  - African diary.

PMID- 7718995
TI  - Anaesthesia and recovery.

PMID- 7718994
TI  - Man behind the instrument (12). Auacestus, Joll Cecil (1885-1945).

PMID- 7718996
TI  - Toward 2001. The recovery room revisited.
AB  - Recovery room nursing is more accurately described by the term "post-anaesthesia
      nursing." Issue of patient safety, standards of care and staff training in the
      recovery room have been highlighted by the Association of Anaesthetists in two
      reports. Current training and education provision for post-anaesthesia nurses is
      provided by combined operating department nursing and anaesthetic nursing
      curricula (ENBI182:83). There are few courses designed for nurses who specialize
      in the care of the post-anaesthesia patient.

PMID- 7718997
TI  - Clinical risk management. Building provider awareness in the administration of
      anaesthesia.
AB  - The area of anaesthesia has long been the focus of risk management concerns. This
      article will address a case study based on some of the high risk issues. Although
      the environment in which anaesthesia is administered is usually a carefully
      controlled area, the anaesthetic agents and the patient's response to them can be
      unpredictable. Injuries sustained as a result of anaesthetic administration and
      anaesthesia can be serious with life-long and costly disabilities and even death.
      Tables 1 and 2 highlight the Risk Management areas to address in anaesthesia and
      Tables 3 and 4 the risk issues which have occurred from over 20 years experience
      in the USA. (MMI Companies Inc. 1993). Many of these issues will be discussed in
      the case study scenario. Further reading around the risk issues will also be
      suggested.

PMID- 7718999
TI  - Encyclopedia of the mouse genome IV.

PMID- 7718998
TI  - Mouse chromosome 1.

PMID- 7719001
TI  - Mouse chromosome 8.

PMID- 7719000
TI  - Mouse chromosome 7.

PMID- 7719002
TI  - Mouse chromosome 9.

PMID- 7719003
TI  - Mouse chromosome 10.

PMID- 7719004
TI  - Mouse chromosome 11.

PMID- 7719005
TI  - Mouse chromosome 12.

PMID- 7719006
TI  - Mouse chromosome 13.

PMID- 7719007
TI  - Mouse chromosome 14.

PMID- 7719008
TI  - Mouse chromosome 15.

PMID- 7719009
TI  - Mouse chromosome 2.

PMID- 7719010
TI  - Mouse chromosome 16.

PMID- 7719011
TI  - Mouse chromosome 17.

PMID- 7719012
TI  - Mouse chromosome 18.

PMID- 7719013
TI  - Mouse chromosome 19.

PMID- 7719014
TI  - Mouse X chromosome.

PMID- 7719015
TI  - Master locus list.

PMID- 7719016
TI  - Mouse chromosome 3.

PMID- 7719017
TI  - Mouse chromosome 5.

PMID- 7719018
TI  - Mouse chromosome 6.

PMID- 7719019
TI  - A high-resolution linkage map of the lethal spotting locus: a mouse model for
      Hirschsprung disease.
AB  - Mice homozygous for the lethal spotting (ls) mutation exhibit aganglionic
      megacolon and a white spotted coat owing to a lack of neural crest-derived
      enteric ganglia and melanocytes. The ls mutation disrupts the migration,
      differentiation, or survival of these neural crest lineages during mammalian
      development. A human congenital disorder, Hirschsprung disease (HSCR), is also
      characterized by aganglionic megacolon of the distal bowel and can be accompanied
      by hypopigmentation of the skin. HSCR has been attributed to multiple loci acting
      independently or in combination. The ls mouse serves as one animal model for
      HSCR, and the ls gene may represent one of the loci responsible for some cases of
      HSCR in humans. This study uses 753 N2 progeny from a combination of three
      intersubspecific backcrosses to define the molecular genetic linkage map of the
      ls region and to provide resources necessary for positional cloning. Similar to
      some cases of HSCR, the ls mutation acts semidominantly, its phenotypic effects
      dependent upon the presence of modifier genes segregating in the crosses. We have
      now localized the ls mutation to a 0.8-cM region between the D2Mit113 and
      D2Mit73/D2Mit174 loci. Three genes, endothelin-3 (Edn3), guanine nucleotide
      binding protein alpha-stimulating polypeptide 1 (Gnas), and phosphoenolpyruvate
      carboxykinase (Pck1) were assessed as candidates for the ls mutation. Only Edn3
      and Gnas did not recombine with the ls mutation. Mutational analysis of the Edn3
      and Gnas genes will determine whether either gene is responsible for the neural
      crest deficiencies observed in ls/ls mice.

PMID- 7719020
TI  - Variation of short tandem repeats within and between species belonging to the
      Canidae family.
AB  - Frequency distribution and allele size in 20 canine microsatellite loci were
      analyzed in 33 flat-coated retrievers, 32 dachshunds, 10 red foxes, and 10 Arctic
      foxes. Overall, the major difference between the two dog breeds was the relative
      allele frequencies rather than the size ranges of alleles at the individual
      locus. The average heterozygosity within the two dog breeds was not significantly
      different. Since the average heterozygosity at several polymorphic loci is a
      relative measure of heterogeneity within the population, analysis of
      heterozygosity within microsatellite loci is suggested as a measure for the
      diversity of populations. Eighty percent (16 of 20) of the canine microsatellite
      primer pairs amplified corresponding loci in the two fox species. This reflects a
      very high sequence conservation within the Canidae family relative to findings
      in, for instance, the Muridae family. This indicates that it will be possible to
      utilize the well-characterized fox karyotype instead of the dog karyotype as a
      step towards physical mapping of the dog genome. Analysis of exclusion power and
      probabilities of genetic identity between unrelated animals by use of the seven
      most informative loci demonstrated that it will be possible to assemble a panel
      of microsatellite loci that is effective for parentage analysis in all breeds.

PMID- 7719021
TI  - Molecular markers near two mouse chromosome 13 genes, muted and pearl, which
      cause platelet storage pool deficiency (SPD).
AB  - The recessive muted (mu) and pearl (pe) mutations on Chromosome (Chr) 13 cause
      pigment dilution and platelet storage pool deficiency (SPD) in mice. In addition,
      mu causes inner ear abnormalities and pe has symptoms associated with night
      blindness. Using an interspecific backcross involving the wild-derived Mus
      musculus musculus (PWK) stock, we have mapped 33 microsatellite markers and four
      cDNAs relative to mu, pe, and another recessive mutation, satin (sa). Analyzing a
      total of 528 backcross offspring, we found tight linkage between the pigment loci
      and several microsatellite markers (D13Mit87, D13Mit88, D13Mit137 with mu; and
      D13Mit104, D13Mit160, D13Mit161, and D13Mit169 with pe). These markers should aid
      the eventual molecular identification of these specific SPD genes.

PMID- 7719024
TI  - Construction of a porcine YAC library and mapping of the cardiac muscle ryanodine
      receptor gene to chromosome 14q22-q23.
AB  - Large-scale physical mapping of the porcine genome has been limited because up to
      now no suitable genomic libraries for this purpose have been available.
      Therefore, we have constructed a yeast artificial chromosome (YAC) library from
      porcine lymphocytes. The library was cloned in the amplifiable vector pCGS966. A
      total of 10080 YAC clones was obtained and has been ordered into 105 96-well
      microtiter plates. An average insert size of 300 kb was calculated from the
      analysis of 78 randomly selected clones, giving a one-fold coverage of the
      porcine genome. To analyze the complexity, we have screened the library for five
      different genes and isolated four different clones containing parts of three of
      these genes. One YAC clone harboring parts of the porcine cardiac muscle
      ryanodine receptor (RYR2) gene allowed us to assign this locus to Chromosome
      (Chr) 14q22-q23. The data were confirmed by PCR analysis of a rodent-porcine
      hybrid cell panel.

PMID- 7719022
TI  - Genetic map of rat chromosome 5 including the fatty (fa) locus.
AB  - Thirteen loci, including the obesity gene fatty (fa), were incorporated into a
      linkage map of rat Chromosome (Chr) 5. These loci were mapped in obese (fa/fa)
      progeny of a cross between BN x 13M-fal+F1 animals. Obese rats were scored for BN
      and 13M alleles at four loci (Ifna, D1S85h, C8b, and Lck1) by restriction
      fragment length polymorphisms and at eight additional loci (Glut1, Sv4j2, R251,
      R735, R980, R252, R371, and R1138) by simple sequence length polymorphisms
      (SSLP). The resulting map spans 67.3 cM of Chr5, presenting nine previously
      unmapped loci and one locus (Lck1) previously assigned to Chr 5 by use of somatic
      cell hybrid lines. Seven of the eight SSLP loci are newly identified; the SSLP
      linkage group alone spans 56.8 cM. The order of the loci is Sv4j2-R251-R735-R980
      R1138-Ifna-fa-+ ++D1S85h-C8b-(Glut1-R252-R371)-Lck1. One locus, D1S85h, was found
      to lie only 0.4 cM from fa, close enough to serve as a reliable marker for the
      prediction of phenotype from genotype, and will be useful also for studies on the
      development of obesity in the fatty rat.

PMID- 7719023
TI  - Genetic map of the region surrounding the retrovirus restriction locus, Fv1, on
      mouse chromosome 4.
AB  - The Friend virus susceptibility-1 (Fv1) gene maps to mouse Chromosome (Chr) 4
      close to a cluster of four endogenous murine leukemia viruses (MLVs). To
      investigate the feasibility of cloning Fv1 by a positional approach, we have
      performed an extensive genetic analysis of this region of Chr 4. We have typed
      368 backcross mice for the four proviruses, Nppa, Lck, and D4Smh6b. Recombinant
      animals were screened in a hierarchical fashion with a variety of other markers,
      including Fv1 and the isozyme marker Gpd1. A detailed genetic map of the region
      surrounding Fv1 was derived. Three markers, Xmv9, Nppa, and Iap3rc11, were
      identified that showed no recombination with Fv1. By combining backcross and
      recombinant inbred strain data, we estimated that Xmv9 and Nppa must lie within
      0.6 cM of one another and Fv1.

PMID- 7719025
TI  - Mapping of human and murine genes for latent TGF-beta binding protein-2 (LTBP2).
AB  - A novel gene, isolated because of structural similarities to fibrillin, was
      called LTBP2 when its 4.6-kb transcript was found to encode a protein sequence
      related to the latent TGF-beta binding protein (LTBP1), which is encoded on human
      chromosome (Chr) 2, region p12-q22. We have assigned the human and murine LTBP2
      loci to regions of conserved synteny on human Chr 11 and mouse Chr 19. By PCR
      analysis of somatic cell hybrid DNA and fluorescence in situ hybridization, LTBP2
      was mapped to human Chr band 11q12 and Ltbp2 to mouse Chr band 19B. Differences
      between inbred strains were discovered by single-strand conformation analysis of
      PCR products from the 3' untranslated region. Analysis of BXD and AKXL
      recombinant inbred strains have placed Ltbp2 between D19Rp19 and Ly10 on proximal
      mouse Chr 19.

PMID- 7719026
TI  - Human chromosome 10 loci map to three different sheep chromosomes.
AB  - The interleukin 2 receptor (IL2RA), a human Chromosome (Chr) 10p locus, was
      mapped to sheep Chr 13q12-q15 by in situ hybridization. Two loci from human Chr
      10q, cytochrome P450 subfamily XVII (CYP17) and the tachykinin 2 receptor
      (TAC2R), were assigned to sheep Chrs 22q21-q23 and 25q14-q23 respectively. The
      assignment of IL2RA allows the provisional assignment of the previously
      unassigned sheep syntenic group U15 to sheep Chr 13. Sheep linkage group 5 is
      predicted to be located on sheep Chr 25 on the basis of the TAC2R assignment.

PMID- 7719027
TI  - SINE elements of carnivores.

PMID- 7719029
TI  - Localization of the corticotropin-releasing hormone receptor gene on mouse
      chromosome 11.

PMID- 7719028
TI  - Mapping of acidic epididymal glycoprotein (Aeg) genes to mouse chromosome 17.

PMID- 7719030
TI  - Assignment of the BM203 DNA segment to U16 bovine synteny group by PCR.

PMID- 7719031
TI  - Comparison of primary structure of a neuron-specific protein, X11, between human
      and mouse.

PMID- 7719032
TI  - Chromosomal localization of the large subunit of mouse replication factor C in
      the mouse and human.

PMID- 7719033
TI  - New localization of NCAM, proximal to DRD2 at chromosome 11q23.

PMID- 7719034
TI  - Assignment of a rat liver Na+/bile acid cotransporter gene to chromosome 6q24.

PMID- 7719035
TI  - Assignment of the porcine acrosin gene, ACR, to chromosome 5p15 by fluorescence
      in situ hybridization (FISH).

PMID- 7719036
TI  - The deafness locus (dn) maps to mouse chromosome 19.
AB  - The deafness mouse has profound sensorineural hearing loss with degeneration of
      hair cells soon after birth. The mode of inheritance is recessive, and there are
      no associated phenotypic anomalies. Thus, this mouse provides a model for
      recessive, non-syndromic, prelingual deafness. We have mapped the gene causing
      deafness in the mouse to Chromosome (Chr) 19 by analysis of 230 intersubspecific
      backcross progeny. No recombinants were found with the microsatellite marker
      D19Mit14. The loci for two guanine nucleotide-binding proteins are tightly linked
      to this marker, and they are being investigated as possible candidate genes. The
      identification of the defective gene in the mouse will help to explain the
      mechanism that causes hair cell degeneration and is likely to identify a
      homologous gene for deafness in humans.

PMID- 7719037
TI  - IgA anaphylactic transfusion reactions.
AB  - IgA anaphylactic transfusion reactions are rare events, estimated to occur in 1
      in 20,000 to 47,000 transfusions. The signs and symptoms of these reactions do
      not differentiate them from other causes of anaphylaxis. The diagnosis of an
      anaphylactic transfusion reaction is established by showing an IgA-antibody in
      the patient's serum. Most laboratories that test for IgA antibodies rely on the
      PHA method, which uses red blood cells that are coated with serologically defined
      IgA multiple myeloma proteins. We tested sera referred from Red Cross regional
      blood centers and hospitals from patients with suspected IgA anaphylactic
      reactions and found an IgA antibody in 76.3% of IgA-deficient patients. However,
      only 17.5% of all samples referred contained an IgA antibody, indicating that
      most persons with suspected IgA anaphylactic reactions had experienced acute
      generalized reactions that were from causes other than anti-IgA transfusion.
      Using PHIA to measure serum concentrations of IgA and PHA to detect IgA
      antibodies, we found the frequency of IgA deficiency (< 0.05 mg/dL) and class
      specific anti-IgA in random blood donors to be approximately 1 in 1,200. Titers
      of anti-IgA did not distinguish these seemingly healthy blood donors from
      patients with a history of an anaphylactic transfusion reaction. Because the
      frequency of 1 in 1,200 greatly exceeds the observed frequency of anaphylactic
      reactions in transfused persons, we conclude that using PHA for anti-IgA does not
      reliably predict risk for an anaphylactic transfusion reaction. Additional
      research is needed to define a more specific marker to identify those persons who
      are truly at risk for these serious, but rare, complications of blood
      transfusion.

PMID- 7719038
TI  - Paid-versus-volunteer blood donation in the United States: a historical review.
AB  - Several points are clear from this historical review. Over 50 years ago the first
      indications that hepatitis could be transmitted from the serum or plasma of one
      human to another became evident. This was confirmed in human transfer experiments
      although the agent causing hepatitis was not known and there was no specific test
      for what eventually was presumed to be a virus. It soon became clear that
      hepatitis was a complication of blood and plasma transfusion. Over the course of
      10 to 20 years (the 1950s and 1960s) the connection was made between
      posttransfusion hepatitis and certain high-risk donors and behaviors. Despite the
      availability of scientific data to support the idea that not all commercial or
      paid blood donors were associated with higher rates of post-transfusion
      hepatitis, public opinion and emotions seemed to be a major driving force behind
      increased government regulation of blood banking. Because there were commercial
      blood banks that continued to recruit, collect, and pay blood donors from low
      income, skid row areas, despite the mounting evidence that such donors clearly
      harbored higher rates of hepatitis, all commercial blood banks were reduced to
      that common denominator. Clearly economic factors were also being thrown into the
      equation. Political and philosophical differences between the major professional
      organizations involved in blood procurement and recruitment were important
      factors favoring more government control. The public pressured politicians and
      government agencies for more regulation and many scientific and medical
      professionals requested greater regulation. By the early 1970s the die was cast
      for increased regulation by the federal government.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7719039
TI  - Transfusion medicine issues in the practice of anesthesiology.

PMID- 7719040
TI  - The role of leukodepletion in the control of transfusion-transmitted disease.

PMID- 7719041
TI  - [Monitoring sewage plants by the public health office].
AB  - According to the Federal law concerning the prevention and control of epidemics
      (Bundes-Seuchengesetz) and according to the third enforcement law about the
      standardisation of the public health system (Dritte Durchfuhrungsverordnung zum
      Gesetz uber die Vereinheitlichung des Gesundheitswesens) it is incumbent upon the
      local Public Health Authorities to supervise the sewage treatment plants within
      their respective administrative district. In practice, that task is hardly ever
      realised since it is often not clear exactly which hygienic aspects should be
      checked and what the benefit of such supervision could be. The following paper is
      an attempt to make suggestions how to carry out such supervising activities in
      practice. Furthermore, the paper shows the results of the 1993 supervising
      activities in the sewage treatment plants in the Limburg-Weilburg area. This is
      illustrated on the basis of the checklist which has been developed at the public
      health office of Limburg.

PMID- 7719042
TI  - [Some comments on public health service and city health planning].
AB  - This paper gives a short presentation on some of the difficulties a public health
      officer has to face concerning questions of town-planning. The focus is on giving
      an expert opinion on development plans. It may be said that the public health
      service and "health" often play minor roles in town planning. The article
      presents some suggestions for a change of this situation.

PMID- 7719043
TI  - [Utilization of social departments before and after effectiveness of the 'need
      for disability care' health service reform in Mannheim].
AB  - Constituting a part of the new health reform in Germany
      ("Bundesgesundheitsreformgesetz"), a new arrangement to support home care for the
      very frail and severely disabled took effect in 1991. Since then the costs of
      basic nursing care and home-making services are partly covered by health
      insurance. To examine the impact of the new arrangement on the use of the
      community nursing services (the so-called "Sozialstationen") we compared two
      cross-sections of elderly patients under care in the city of Mannheim. The cross
      sections encompassed all over 65-year old patients visited during January 1990
      (first cross-section) and during May 1993 (second cross-section) by the
      "Sozialstationen" in Mannheim. The characteristics of the patients (degree of
      disability in everyday life, level of cognitive functioning etc.), together with
      the forms of care provided, were recorded by the nurses. The results show that
      the number of patients cared for by the "Sozialstationen" was smaller in May 1993
      (n = 1649) than in January 1990 (n = 1842); especially the number of the severely
      disabled and demented patients was reduced. Although these findings can be viewed
      only as preliminary, one can conclude that--contrary to all expectations--there
      was no run on the "Sozialstationen" in the course of the implementation of the
      new social code.

PMID- 7719044
TI  - [Patient satisfaction as a criterion of quality assurance in inpatient
      psychosomatic rehabilitation].
AB  - The investigation of patient satisfaction with treatment by means of simple
      standardised self-rating instruments is a focal point of monitoring and
      improvement of treatment quality in the programme of quality assurance of
      rehabilitation within the statutory social insurance system. In the field of
      psychosomatic rehabilitation this criterion contains a number of problems due to
      the individual traits of patients, the treatment institutions, and the
      rehabilitation process. A structural discrepancy between the patients' attitudes
      and the requirements of the rehabilitation measure causes a systematic potential
      of dissatisfaction of the patients throughout the whole rehabilitation procedure.
      The specific quality of psychosomatic rehabilitation requires differentiation in
      the assessment and interpretation of patient satisfaction as a criterion of
      quality assurance as well as in the deduction of subsequent measures for
      improvement. Doubts are also raised as to the usefulness of a simple and global
      reference to patient satisfaction as a criterion of quality assurance even beyond
      the field of psychosomatic rehabilitation.

PMID- 7719045
TI  - [Regional distribution of leukemia incidence in children in West Germany 1975
      1990].
AB  - The actual debate on temporal or regional clustering of childhood leukaemias
      includes an intensive discussion, whether or not the observed patterns of
      frequency distribution are governed merely or mainly by random processes. With
      the "Information System on Cancer Mortality and District Characteristics (IKK)"
      the Cumulative Mortality Rates of childhood leukaemias (up to age 15) are
      determined for the single district authority units (Kreis) in the Federal
      Republic of Germany (old Laender) between 1975 and 1990. The frequency
      distributions of the mortality rates as well as the dependencies on population
      density are analysed. No statistical significance for a deviation from the
      corresponding mere random distributions could be revealed.

PMID- 7719046
TI  - [Frequency analysis for achieving health goals--I: Standardization].
AB  - The formal mathematical steps of direct and indirect standardisation are deduced
      and it is pointed out that standardisation is an analytical concept for
      processing data within the framework of structurised populations to enable
      correct interpretation of these data in a manner modified according to specific
      problems. In particular, this concept is not confined to transforming age
      structured mortality data of a population to the age distribution of the members
      of a larger population by means of a rule of three. Standardisation is in fact a
      model of the macrolevel (population). It makes no demands on the modalities of
      structuring. The structure selected as standard is arbitrarily set. With time
      series, standardisation usually modifies only the levels of the figures and not
      the frequencies. The results of standardisation are in every case valid only if
      the standard is also stated. A rule of thumb is: In retrospective analysis it is
      meaningful to standardise on the structure at the beginning or end of the time
      series; in extrapolations standardisation should be performed on the last
      structure that had been determined, whereas for comparisons a median structure
      should be standardised. The standardisation approach can be used in case of
      weighted arithmetic, geometric or harmonic means. Before effecting
      standardisation, the type of connection between the employed data should be
      examined. The examples of concepts of direct standardisation refer to
      cardiovascular and accident mortality in West Berlin from 1963 to 1991, whereas
      those of indirect standardisation are based on the accident mortality in West
      Berlin in 1987 structured according to city districts.

PMID- 7719047
TI  - [Worries about the job, unemployment and health status--initial results of a
      study in Saxony].
AB  - 1628 patients of general practitioners in Saxonia were asked and clinically
      examined in 1993 to find out the context between unemployment and health
      conditions. Surprisingly, the working people who "only" worry about losing their
      jobs were more concerned than the unemployed ones. However, more than 50% of the
      women and 41% of the men were troubled by this problem. The worried people
      reported about 23% a bad health condition but only 20.5% of the unemployed and
      14% of the working people who had no fear of losing their place of work. In
      addition, those who were worried suffered from high social strain and more
      chronic diseases. In East Germany, this population is more disposed to health
      risks than any other one today, especially the unemployed. The family doctors
      will often be the first and only persons who will be able to recognise these
      connections.

PMID- 7719048
TI  - [Secondary prevention of sexually transmissible diseases in public health service
      -analysis of initial experiences in a Bremen counselling office of the chief
      public health office].
AB  - Medical activities of the Public Health STD programme in Bremen were analysed
      during a period of one year. This experimental project comprises various
      activities on primary prevention, counselling services, including streetwork, on
      social and health issues related to sexual health and confidential, anonymous
      diagnosis and treatment of STD. 621 examination in 248 patients were evaluated.
      The need for STD screening and treatment has not yet been assessed in Bremen.
      Nevertheless, a considerable number of individuals considered themselves in need
      for STD screening or treatment in a public health setting. In comparison with
      1975-1985, when bimonthly mandatory screening on female prostitutes was common in
      Bremen, the number of examinations declined by a factor of ten, whereas the
      actual number of treated persons remained stable. Of all examinations, 511
      (82.3%) were carried out on females, 110 (17.7%) on males, 351 (56.5%) on German
      citizens and 270 (43.5%) on clients with foreign citizenship. 461 (74.2%) of all
      examinations involved female prostitutes. Sexually transmitted diseases were
      shown to be present in 39.3% (244/621) of the examinations. In addition,
      "vaginitis" was found in 47.7% of gynaecological checks. The STD prevalence was
      extraordinary high in female drug-addicted (75%) and foreign prostitutes (40.6%).
      Only in foreign prostitutes a significant association between incidence of STD
      and age was found. Costs in relation to the detection of one STD were found to be
      rather low compared to the benefit to the individuals and the society. Therefore,
      the STD/HIV prevention programme should be maintained.

PMID- 7719049
TI  - [Nitrous oxide exposure of operating room personnel in intubation anesthesia].
AB  - INTRODUCTION: Epidemiological studies have shown that trace concentrations of
      inhalation anaesthetics polluting the air of operation theatre could have adverse
      effects on the personnel's health. Nitrous oxide (N2O) oxidizes vitamin B12 and
      thus decreases DNA production by inactivation of methionine synthase. Therefore,
      US and most European health authorities recommend threshold values to protect
      against potential health risks. These values range from 25 ppm to 100 ppm,
      expressed as time-weighted averages (TWA). There is a lack of data concerning
      measurements of trace concentrations under defined conditions. The aim of this
      study was to quantify levels of N2O in an operating theatre (OT) under modern
      working environment conditions. METHODS: Trace concentrations of N2O were
      determined in the OT at three personnel-related and three potential leakage
      related points and TWA's were calculated. Trace concentrations of N2O were
      measured directly by means of a highly sensitive photoacoustic infrared
      spectrometry analyser. The lower detection limit was 0.03 ppm. RESULTS: Values
      were below 100 ppm TWA at personnel-related locations. NIOSH 25 ppm threshold
      limit value was exceeded several times. Significant differences between location
      surgeon and anaesthetist and auxiliary nurse were detected (p < 0.05, Wilcoxon
      test). CONCLUSION: Exposure to N2O in a climatised OT is determined by several
      factors: 1. Efficacy of the air-conditioning with 20 changes per hour without
      recirculation, 2. OT size, 3. low leakage anaesthesia machine, and 4. avoidance
      of intermittent nitrous oxide supply during induction. Due to these factors, most
      measured values are below threshold values. In case of other concepts of room
      design such as ventilation and size, measured values may be higher.

PMID- 7719051
TI  - AHNA certificate program in holistic nursing courses. AHNA certificate program in
      healing touch courses.

PMID- 7719050
TI  - [Microbial contamination of immersed massage devices].
AB  - Investigations in the District of Schaumburg. On the occasion of the inspection
      of a hospital we became aware of the problem of contamination of underwater
      massage tubs with microorganisms. Hence, investigations according to the German
      DIN standard 19,643 were performed on 41 tubs. Very often we found a high count
      of microorganisms. If Pseudomonas aeruginosa was detected, the use of the
      respective tub was prohibited because of the risk of infection (about 70% of all
      tubs). The reasons are the design of the pumps and different procedures of
      cleaning and disinfection. During the investigations the suppliers of the
      apparatus were queried. In some cases, technical improvements have already been
      effected. Reliable standard disinfection procedures must be developed.

PMID- 7719052
TI  - China trip teaches art of leadership.

PMID- 7719053
TI  - Nursing in the year 2010.

PMID- 7719054
TI  - The responsive touch of ancient healing energy: a promising alternative in
      rehabilitative therapy.

PMID- 7719055
TI  - Socially responsible investing.

PMID- 7719056
TI  - Adaptation to group home living for adults with mental retardation as a function
      of previous residential placement.
AB  - Changes in adaptive functioning subsequent to a group home placement was assessed
      for deinstitutionalized and previously non-institutionalized adults with mental
      retardation. Results indicated that both groups experienced a significant
      increase in overall adaptive functioning subsequent to group home placement. The
      results also indicated that neither group experienced a significantly greater
      increase in adaptive behaviour compared to the other. Additionally, it was found
      that the deinstitutionalized group functioned at a higher adaptive level overall
      than did the previously non-institutionalized group. These results are consistent
      with previous research regarding the benefits of a group home placement on
      deinstitutionalized individuals. This research extends previous research by
      demonstrating that group home placements also have a significant impact on the
      adaptive behaviour of previously non-institutionalized individuals.

PMID- 7719057
TI  - Medical aspects of ageing in a population with intellectual disability: I. Visual
      impairment.
AB  - Visual function of an institutionalized population with intellectual disability,
      consisting of 70 subjects with a mean age of 70.1 (range 60-92) years at initial
      evaluation, was assessed during a 10-year prospective longitudinal study. One
      subject had Down's syndrome and could not be assessed as a result of dementia.
      Lower visual acuity values were relatively overrepresented as compared to
      reported data from ageing populations without intellectual disability. In
      addition, the prevalence of moderate to severe visual impairment was distinctly
      higher (27.9% in the group studied vs. 0.66% at age 60-69 years to 13% over age
      80 in a population without intellectual disability). During follow-up, visual
      function improved in three out of 61 subjects (4.9%) after cataract surgery, and
      deteriorated in eight out of 61 subjects (13.1%), even with optimal correction,
      as a result of cataract and macular degeneration. Causes of excess impairment
      were congenital or childhood conditions, too-late diagnosis of glaucoma and
      suboptimal correction of refractive errors in non-cooperative individuals. The
      present author concludes that it should be possible to reduce excess impairment
      by an active diagnostic and therapeutic attitude to subjects from a young age
      onwards.

PMID- 7719058
TI  - Medical aspects of ageing in a population with intellectual disability: II.
      Hearing impairment.
AB  - Hearing function of an institutionalized population with intellectual disability,
      consisting of 70 subjects with a mean age of 70.1 (range 60-92) years at initial
      evaluation, was assessed during a 10-year longitudinal study. One subject had
      Down's syndrome and could not be assessed as a result of dementia. The total
      prevalence of mild to severe hearing loss (33.3% in the 60-70 age group and 70.4%
      in those over age 70) was comparable to reported data from an ageing population
      without intellectual disability in the United Kingdom (37%, respectively 60%).
      However, the proportion of moderate to severe losses might be higher (16.7% vs.
      7% in the 60-70 age group and 33.3% vs. 18% in the older age group). Excess
      impairment was caused by severe congenital and childhood hearing impairment on
      one hand, and by conductive losses, probably caused by unrecognized chronic
      middle ear infections, superposed upon presbyacusis, on the other. Impacted ear
      wax was also a major problem. The incidence of new cases with hearing loss during
      follow-up was 50%. After individual habituation training hearing aids were used
      without difficulties by 20 out of 24 subjects. The importance of active screening
      and treatment of middle ear infections and hearing impairment from a young age
      onwards, and regular cleaning of the external ear canals is stressed.

PMID- 7719059
TI  - Staffing and staff performance in services for people with severe or profound
      learning disability and serious challenging behaviour.
AB  - Eighteen people with severe or profound learning disability and very serious
      challenging behaviour were tracked for four and a half years. Thirteen subjects
      moved to staffed houses in the community. A multiple time-series design and
      direct observation were used to evaluate whether there was any change in staffing
      and staff contact. The houses had higher staff ratios and proportionately even
      higher levels of assistance and other contact with clients, who showed
      significant improvement in engagement in meaningful activity without overall
      increase in major problem behaviour.

PMID- 7719060
TI  - Sexual knowledge interview schedule: reliability.
AB  - The Sexual Knowledge Interview Schedule (SKIS) is a 46-item interview schedule
      with an abuse scale and knowledge scale. The knowledge scale includes feelings,
      body parts identification, body parts function and general sexual knowledge. The
      reliability of the SKIS is reported. Internal consistency for scales/subscales
      ranges from 0.78 to 0.96. Inter-rater reliability was 95.3% agreement and test
      retest reliability was 70.1%.

PMID- 7719061
TI  - Symptoms of major depression in mentally retarded adults.
AB  - A total of 32 mentally retarded adults currently suffering from major depression
      were examined for the prevalence of typical and atypical depressive symptoms. In
      contrast to persons with severe mental handicap, all those with mild handicap
      could be assessed using almost all DSM-III-R diagnostic criteria. A depressive
      syndrome with increased irritableness and psychomotor agitation was found in more
      cases of severe than mild handicap. Both groups revealed atypical symptoms; these
      were more frequent amongst the severely handicapped. The atypical symptoms were
      mostly emerged or increased behaviour problems, and rarely a loss of adaptive
      behaviour. The onset of new behaviour problems appeared equally in both groups,
      whereas an increase in existing behaviour problems seems typical for severe
      handicapped subjects. The diagnosis of major depression in mentally retarded
      adults should consider these features.

PMID- 7719062
TI  - Methodological aspects of life events research in people with learning
      disabilities: a review and initial findings.
AB  - A review of the life events studies relevant to people with learning disabilities
      is discussed. Issues surrounding the collection of information by using a
      structured interview method as set out in the Life Events and Difficulties
      Schedule Manual and the adjustment of threat rating to accommodate the
      perspective of people with learning disabilities are presented as a result of
      conducting a pilot study. The importance of using a probing interview style in
      contrast to a checklist method and eliciting the parents/carers' perception of
      events is emphasized.

PMID- 7719063
TI  - Theories of ability and the pursuit of challenge among adolescents with mild
      mental retardation.
AB  - Dweck (1991) distinguishes two different ways children can view their abilities.
      Children who have an 'incremental theory' of their ability believe that it is a
      changeable, increasable and controllable quantity. Those who have an 'entity
      theory' believe their ability represents a fixed, unchangeable trait. Children
      with an 'incremental theory' tend to display adaptive achievement behaviours such
      as pursuing challenging activities, whereas children with an 'entity theory' tend
      to avoid challenges. The present study examined the usefulness of this
      distinction in understanding the behaviour and affect of children with mental
      retardation in an achievement situation. Results from an attributional
      questionnaire showed that children with mental retardation were significantly
      less likely to possess an incremental theory of their abilities than children
      without retardation. However, experimental results showed that when the context
      highlighted an incremental theory of ability, children with mental retardation
      showed the same positive motivational response as children without retardation
      (i.e. they chose high levels of challenge and reported greater interest
      enjoyment). One unexpected finding emerged: children with mental retardation
      showed a tendency to choose lower challenge levels after receiving verbally
      administered success feedback relative to neutral feedback.

PMID- 7719064
TI  - Providing intensive community support to people with learning disabilities and
      challenging behaviour: a preliminary analysis of outcomes and costs.
AB  - The impact of a specialist community service on the lives of three people with
      challenging behaviour was assessed using single-case studies. The outcome
      measures employed recorded changes in adaptive behaviours, challenging behaviours
      and staff satisfaction with the interventions used. Improvements on the
      behavioural measures were observed for each client, and positive feedback was
      received from each of the staff groups concerned. The costs of providing these
      interventions in community settings were calculated and compared to the costs of
      alternative service options.

PMID- 7719065
TI  - Long-term survival in the Wolf-Hirschhorn (4p-) syndrome.
AB  - The clinical features of Wolf-Hirschhorn syndrome are described in a 29-year-old
      woman who shows severe retardation of growth and development. It is important for
      health care professionals involved with families in which this condition is
      present to realize that long-term survival may occur.

PMID- 7719066
TI  - [Recent vitrectomy indications].

PMID- 7719067
TI  - [Morphology of the Meibomian lipid film. Results of Brewster angle microscopy].
AB  - Meibomian lipid layers were studied in the anterior mirror area by reflecting
      microscopy and interference microscopy. Using these techniques, it was not
      possible to correlate the biophysical and morphological data. Brewster angle
      microscopy provides direct observation of the spread Meibomian lipid layer with
      simultaneous registration of the surface pressure. It is based on the fact that
      He-Ne laser light, which is incident at a water surface under the Brewster angle,
      does not reflect visible light. After spreading of a lipid film, the angle of the
      incident light beam varies, causing reflection of light. The Meibomian lipid
      layer was studied in a Langmuir-type trough. At 5.0 mN/m the lipid layers are
      homogeneous and mobile, consisting of areas of higher and lower reflectivity. In
      patients with meibomitis the films are inhomogeneous and immobile. The thickness
      of the areas of lower reflectivity is 2 nm, the high reflectivity lipids are 8-10
      nm thick. According to these results, Meibomian gland secretion can form
      monolayers under in vitro conditions.

PMID- 7719068
TI  - [Isotretinoin administration in treatment of acne vulgaris. A prospective study
      of the kind and extent of ocular complications].
AB  - Isotretinoin (13-cis-retinoic acid) is commonly used for the treatment of acne
      vulgaris. In the skin this substance causes an atrophy of sebaceous gland acini
      and a decrease in sebum production. Systemic treatment also alters meibomian
      gland function and structure. These alterations seem to be responsible for ocular
      complications (dryness of the eye, blepharitis, conjunctivitis) during therapy
      with isotretinoin. We inspected 30 patients before, during and after therapy with
      isotretinoin with regard to ocular side effects. Examination included careful
      slit-lamp inspection, measurement of break-up time (BUT) and the Schirmer test.
      Conjunctival smears were taken from every patient. The most frequently observed
      side-effects were decreased tear break up time and alterations of the lid margin.
      In addition, an enormous increase of Staphylococcus aureus in conjunctival flora
      was noticed. However, all ocular complications of systemic treatment with
      isotretinoin were reversible after cessation of therapy.

PMID- 7719069
TI  - [Age-dependent distribution of Langerhans cells within human conjunctival
      epithelium].
AB  - Non-pathological conjunctival specimens (240) were used for evaluation of
      Langerhans cell (LC) numbers per square millimeter. Of the 240, 60 were taken
      from each of four age groups (1-20 years, 21-40 years, 41-60 years, 61 years and
      older). In each group, 20 came from the bulbar conjunctiva (lateral superior), 20
      from the fornix region (central superior), and 20 from the palpebral conjunctiva
      (central inferior). Quantitative analysis was carried out with the Langerhans
      specific anti-CD1a antibody using APAAP method. Additionally, 40 conjunctival
      specimens were stained with the Tu 36 (all HLA/DR Ag) and the Tu 39 (all HLA/DR, 
      /DP Ag). A basic decline in the density of LC cells corresponding to advancing
      age of the tissue donors was found in all three regions studied (< or = 20 years:
      4.4 LC/mm2; > 60 years: 1.2 LC/mm2). The largest number of LC (4.7 LC/mm2) was
      found in the palpebral conjunctiva (central inferior); 3.1 LC/mm2 were found in
      the fornix (central superior) and 1.0 LC/mm2 in the bulbar conjunctiva (lateral
      superior). As an antigen-presenting cell, the LC plays an important role in
      immune reactions in the area of the superficial ocular epithelium. The data
      gained here can serve as a basis for studies of pathological tissue since, as is
      known from dermatological research, firm relationships exist between specific
      inflammatory or tumorous diseases and LC density in the affected organs.
      Moreover, a direct connection is to be assumed between the success of
      transplantation and LC density in allogenic conjunctival grafts.

PMID- 7719070
TI  - [Correlation between laser tyndallometry and protein concentration in the
      anterior eye chamber].
AB  - The laser flare cell meter (LFCM) is introduced as an instrument that quantifies
      noninvasive anterior chamber protein. The relationship between laser flare
      measurement and actual protein concentration in vivo and in vitro was assessed.
      The intensity of light scattering by helium neon laser beam is measured by LFCM
      and depends on protein concentration and molecular size. Total protein, albumin
      and transferrin were measured using nephelometry and the Coomassie method. We
      tested 63 patients undergoing routine cataract surgery. Laser flare measurements
      were made before surgery. The mean in vivo flare was 8.25 photons/ms, standard
      deviation 9.57 photons/ms. Before surgery paracentesis was performed in 61
      patients. In vitro aqueous flare was 10.55 +/- 7.68) photons/ms. Biochemical
      analysis showed a mean anterior chamber protein concentration in 51 patients of
      33.65 (+/- 27.36) mg/dl, a mean albumin concentration in 38 patients of 15.78 (+/
      11.03) mg/dl, and a mean transferrin concentration in 33 patients of 2.01 (+/-
      0.88) mg/dl. Up to a "cell" count of 40/0.075 mm3 there is a statistically
      significant correlation. Laser flare values compared with biochemical analysis
      showed for total protein a correlation coefficient of r = 0.695 in vivo and r =
      0.753 in vitro. A "cell" count higher than 40/0.075 mm3 produces marked
      overestimation of protein concentration by laser flare values. There is a
      statistical significant linear correlation between photon count by LFCM and total
      aqueous protein concentration by biochemical analysis in vivo and in vitro in
      normal cataractous eyes.

PMID- 7719071
TI  - [Significance of subjective sensitivity in evaluation of keratoconjunctivitis
      sicca].
AB  - In patients with keratoconjunctivitis sicca (KCS) frequently a mismatch between
      the symptoms and clinical signs of impaired tear film is found. Thus, we
      conducted a study to determine whether tests can be found that provide
      information on increased sensitivity in KCS patients. Thirty patients with and
      without KCS were investigated by the following methods: a specific anamnestic
      questionnaire, esthesiometry and provocation of ocular pain by instillation of a
      local anesthetic eye drop. Esthesiometry only showed a shift towards higher
      sensitivity, but the other tests indicated significantly increased ocular
      sensitivity in KCS patients. These very simple methods permit better
      understanding of the specific situation in the individual patient.

PMID- 7719072
TI  - [Monotherapy vs combination therapy with topical prednisolone and indomethacin].
AB  - The anti-inflammatory effects of topical steroids and nonsteroidal anti
      inflammatory drugs (NSAID) are claimed to be additive, according to
      fluorophotometric measurements. This finding was reevaluated using laser flare
      cell photometry. PATIENTS AND METHODS: Thirty patients (61-79 years of age)
      without pre-existing deficiencies of the blood-aqueous barrier were investigated
      preoperatively as well as on day 1 and 3 after ECCE with IOL implantation. The
      laser flare-cell photometer (model FC-1000; Kowa Company) which was used for
      examination enables sensitive and exact in vivo determination of aqueous flare.
      The patients were randomly assigned to one of the following three treatment
      groups: group A, monotherapy with prednisolone 1% eyedrops (Inflanefran forte);
      group B, monotherapy with indomethacin 1% eyedrops (Chibro Amuno); group C,
      combination therapy with prednisolone 1% + indomethacin 1% eyedrops. One drop of
      either drug was administered five times per day to each patient, beginning
      immediately after completion of surgery. In addition, all patients received
      antibiotic therapy with gentamicin. Parabulbar or oral steroids were not
      administered. RESULTS: Under monotherapy with prednisolone, the flare (photon
      counts/ms) on days 1 and 3 postoperatively averaged 30.9 and 27.8, respectively.
      Under indomethacin monotherapy, the flare values were similar (no significant
      differences). Under combination therapy with prednisolone+indomethacin, however,
      the flare values were significantly lower both on day 1 (24.2) and on day 3
      (20.6). CONCLUSIONS: Combination therapy with topical prednisolone+indomethacin
      thus seems superior to monotherapy with either of these agents. This confirms the
      previous fluorophotometric finding that the anti-inflammatory effects of topical
      steroids and NSAID are additive, a phenomenon attributable to different
      pharmacological sites of action.

PMID- 7719073
TI  - [Eye injuries caused by opening or explosion of beverage bottles].
AB  - Exploding beverage bottles can cause serious ocular injuries. The mechanisms of
      injury and the consequences were studied retrospectively in 21 patients admitted
      to the hospital between 1982 and 1992. Most of the patients (76%) were injured by
      propulsion of the bottle cap. Bottle explosions following dropping on the floor
      were the most frequent cause of perforating ocular injuries by glass fragments
      from a beverage bottle. Among our patients, 12 (57%) had severe globe contusions
      and 9 (43%) had lamellar or penetrating globe injuries. In 83% of the contusions,
      100% of the lamellar injuries and 62% of the penetrating eye injuries almost
      complete visual rehabilitation (vision 0.5-1.0) was achieved. Vision was saved in
      all the injured eyes. About 2% of all eye injuries admitted to hospital are
      caused by bottle explosions. The consumer can reduce the danger of bottle
      explosions by storing bottles in a cool place and taking care not to shake then
      before use. Manufacturing industry is called upon to develop and to use stopper
      systems connected to the bottles to prevent propulsion of bottle caps.

PMID- 7719074
TI  - [Ocular findings in Desferal therapy].
AB  - Desferrioxamine (DFO) is the most important drug in the treatment of thalassemia
      major and other hematological diseases requiring regular transfusion. It
      eliminates excessive ferritin by building up chelate complexes. Different
      mechanisms of possible DFO toxicity are induction of oxidation, damage of the
      blood-retina barrier, or reduction in other metalloions (Cu2+, Zn2+). The
      objective of the present study was to evaluate the ocular side effects of DFO
      treatment. We prospectively examined 17 patients aged 5 to 25 years, all of them
      treated with DFO. Visual acuity, pupillary reaction, anterior segment, lens and
      fundus were checked. If possible, visual fields, color vision, dark adaptation,
      stereoscopic vision, and contrast sensitivity were investigated. Lens opacities
      were found in 41% (7/17), changes in the retinal pigment epithelium in 35%
      (6/17), tortuosity of retinal vessels in 24% (4/17), dilation and sheathing of
      the retinal vessels in 18% (3/17), defects in color vision in 29% (5/17), and
      abnormal dark adaptation in 18% (3/17) of the patients. The oculotoxicity of DFO
      is dose-dependent. Major side effects like depression of the visual acuity are
      partially reversible after discontinuing the therapy. Regular ophthalmological
      check-ups are therefore necessary.

PMID- 7719075
TI  - [Monoca silicone intubation of the lacrimal ducts after retrograde dilatation].
AB  - The causes of stenosis in the area of the nasolacrimal duct in adults are
      extremely variable. In general, the symptoms may vary, but most cases exhibit a
      common factor of circumstances in the prestenotic area which favor recurring
      inflammation. The treatment of these disorders is limited to either a
      conservative therapeutic approach to control inflammation, or surgically invasive
      measures. By using balloon catheters, which are usually applied in PTCA
      (percutaneous transluminal coronary angioplasty), dilatation of the relative
      postsaccal stenosis is obtained with the assistance of radiography. An exact
      diagnosis by means of various testing methods, including digital
      dacryocystography for the detailed localization and documentation of any
      pathological changes, is decisive for success. Only in cases of incomplete,
      postsaccal stenosis is retrograde balloon dilation of the distal nasolacrimal
      duct incated. The guide wire, designed for the PTCA balloon catheter set, is
      introduced via the canaliculus to the nasal cavity antegradely and caught with a
      thin hook and pulled from the naris. This is done under visual control using an
      image converter. The balloon catheter is retrogradely threaded over the guide
      wire. The balloon is then placed at the site of the pathological stenosis under X
      ray control and dilated with high pressure. To assure permeability of the system,
      a monocanalicular silicone intubation has to be made immediately following this
      procedure. This procedure has been performed successfully on six patients; Follow
      up time ranged from 6 to 22 months. The initial results are encouraging and
      sustain hope that this minimally invasive, interdisciplinary technique represents
      a new alternative in the treatment of incomplete, postsaccal lacrimal stenosis.

PMID- 7719076
TI  - [Inflammatory cellular infiltration in scleritis].
AB  - BACKGROUND: Scleritis can be a destructive disease frequently associated with
      autoimmune disorders. It is believed that primary vasculitis plays an important
      role in its pathogenesis, but little is known about the cellular effector
      mechanisms. The purpose of this study was to analyze the inflammatory cellular
      infiltrate in scleritis. PATIENTS AND METHODS: Two enucleated eyes were studied.
      In one patient, enucleation was done after perforation occurred in anterior
      necrotizing scleritis and, in the other, after the misdiagnosis of posterior
      scleritis as an intraocular tumor. Morphological criteria and immunohistochemical
      methods were used to characterize the inflammatory cellular infiltrate. RESULTS:
      The cells infiltrating the scleral fibers in the enucleated eyes consisted
      predominantly of T cells in both cases; many of the T cells were CD4-positive.
      Clusters of B cells were found in perivascular areas. In circumscribed areas
      neutrophils, macrophages, and plasma cells were part of the scleral infiltrate.
      Signs of a granulomatous process with activated macrophages (epitheloid and giant
      cells) were present in necrotizing scleritis. Expression of major
      histocompatibility class II molecules (MHC II) was found on lymphocytes and
      rarely on macrophages. Signs of primary vasculitis were not found in any of the
      specimens. CONCLUSION: The cellular infiltrate in scleritis shows, at least at
      certain stages, features compatible with a T-cell mediated (autoimmune) disorder,
      which has major therapeutic implications.

PMID- 7719077
TI  - [New knowledge of echographic imaging of the optic nerve. Experimental and
      clinical studies].
AB  - The optic nerve can be displayed in vivo by A- and B-scan techniques. To achieve
      correlations between the anatomical structure of the optic nerve and the
      echograms and to answer the question if by the usual examination techniques the
      diameter of the nerve can be measured, experimental studies on bovine optic
      nerves were carried out: examination of the bovine optic nerve in vitro with the
      A-scan technique; measurement of the sound velocity in bovine optic nerves.
      Additionally, we compared the two most common A-scan techniques for the display
      of the optic nerve in vivo in 47 normal persons and in 35 patients with changes
      of the optic nerve. The experimental studies showed that the orbital fat and
      outer sheaths of the optic nerve cause refraction of the sound beam. The sound
      velocity of ultrasound in bovine optic nerves was measured to 1567 +/- 25 m/s.
      The two most common examination techniques in vivo showed no differences in
      normal persons, but significant differences in patients with increased
      subarachnoidal fluid.

PMID- 7719078
TI  - [A new syllable text for evaluating near vision].
AB  - When visual acuity for distance is tested correct recognition of (as an example)
      6 of 10 Landolt-rings is required. On the other hand, it is very difficult to
      define visual acuity exactly with reading cards, the result will also depend on
      the patient's reading ability. The new near vision test consists of 10 syllables
      with two letters being calibrated according to DIN 58,220 (part 2 A1-correlation
      of optotypes) by Rassow et al. [11]. The patient is required to recognize 6
      syllables out of 10 correctly. To test crowding phenomena the syllables are
      connected by a letterlike symbol. In 18 patients suffering from squint amblyopia
      and in 18 patients suffering from anisometropic amblyopia visual acuity with
      Oculus reading cards and with the new near vision test was identical. The
      crowding syllables test yielded a visual acuity comparable to that determined
      with the C test according to Haase/Hohmann [6]. The new near vision test makes it
      possible to examine visual acuity for reading with syllables as exactly as for
      single optotypes using Landolt-rings. In both cases, 6 of 10 answers have to be
      correct. Additionally, reading time for one syllable can be restricted to one
      second when patients with nystagmus are being tested.

PMID- 7719079
TI  - [Diagnosis and and differentiation of dry eye disorders].
AB  - Artificial tears often fail in dry eye patients. Our goal was to establish a
      diagnostic approach that involves alternatives that are more effective for the
      treatment. We examined 110 patients with dry eyes not stabilized by artificial
      tears: medical history, visual acuity, slit lamp examination, rose bengal stains
      and fluorescein stains, Schirmer test, break-up time (BUT), dye tests, impression
      cytology, and lid transillumination. This allowed disturbances of the three
      layers of the tear film (lipid, aqueous, mucin) to be differentiated. Cellular
      damage of the ocular surface was evaluated and scored by slit lamp examination,
      rose bengal staining, and impression cytology. Only 8% of the patients with
      "sicca syndrome" had exclusive aqueous deficiencies amenable to artificial tears.
      In contrast, lipid deficiencies (chronic blepharitis) were determined most
      frequently (78%). Twenty-six percent had disturbances in two or more layers of
      the tear film. The diagnostic strategy of differentiating disturbances of the
      layers of the tear film offers a more specific approach to the treatment of dry
      eyes.

PMID- 7719080
TI  - [A new miniaturized flicker test for detection of florid retrobulbar neuritis].
AB  - A new transportable miniaturized flicker test equipped with green LEDs is
      contrasted with the conventional Tubingen flicker test, based on brightness
      perception of intermittent white light. The results are compared with those of
      former studies. In this study we examined 45 eyes suffering from florid optic
      neuritis. Another group of 114 eyes were either normal (except minimal ametropia)
      or suffered from a non-inflammatory or non-refractive impairment of central
      visual function. In all groups only one eye of each subject was examined. Using
      the criteria of Trauzettel-Klosinski, the new miniaturized "green" flicker test
      for the detection of a florid optic neuritis showed a specificity of only 50.9%
      (83.3%) and a sensitivity of 91.1% (64.4%). (The corresponding results of the
      conventional Tubingen flicker test are shown in parentheses.) Alternatively,
      analyzing the data with the help of a logistic regression, the "green" flicker
      test turned out to have a specificity of 92.9% (93.8%) and a sensitivity of 60.5%
      (44.2%). For further examinations using the flicker test it is useful to consider
      the duration and reproducibility of each brightness match by repeating the test
      several times.

PMID- 7719081
TI  - [Effect of traumatic iris defects on spatial perception].
AB  - Perforating injury to the eye often results in iris defects in addition to loss
      of the lens. To determine whether iris defects can impair stereopsis, we tested
      the stereoscopic vision of 23 patients treated at the University Eye Clinic in
      Kiel for perforating eye injuries involving the iris and, in most cases, the
      lens. The patients were divided into three groups according to the severity of
      the iris defect and the status of the intraocular lens. Individuals with
      strabismus or visual acuity < 0.5 (20/40) were excluded. Stereopsis was measured
      using conventional stereopsis tests (Titmus contour stereopsis, Lang global
      stereopsis) and by means of the Pulfrich pendulum phenomenon. Patients with
      traumatic aphakia without an iris defect (n = 33) served as controls. Optical
      rehabilitation was achieved in the controls lenses (n = 16) or intraocular lens
      implant (n = 17). In group I (intact lens, iris defect < 135 degrees), two of
      five patients had attained global stereopsis. In group II (implanted or contact
      lens, iris defect < 135 degrees), only one of the nine patients exhibited global
      stereopsis. In group III (no lens, iris defect > 135 degrees), none of the nine
      patients achieved global stereopsis. In the control group, by contrast, more than
      half of the patients with an implant (10 of 17) and 3 of 16 patients with a
      contact lens attained global stereopsis. The results indicate that severe iris
      defects are especially likely to impair stereoscopic vision, more so than
      traumatic loss of lens alone without an accompanying iris defect.

PMID- 7719082
TI  - [Motility disorders in brachytherapy of choroid melanomas with Ru106
      applicators].
AB  - Accurate visualization of the tumor base by diaphanoscopy is essential for
      optimal placement of a ruthenium plaque. Depending on the localization of the
      tumor, dissection of one or more of the rectus muscles is necessary during
      placement of the plaque or during the course of protracted irradiation. Orthoptic
      investigations were performed to evaluate the cause of motility disorders and to
      follow up the functional outcome. In 13 patients (out of 30) who underwent
      ruthenium-106 therapy for uveal melanomas, one or more muscles had to be
      dissected during placement of the plaque and were reinserted in the same
      operation or after removal of the applicator. In 4 cases rectus muscles had to be
      shifted and were replaced after the irradiation. There were 5 patients who
      developed motility disorders with double vision. All of them were orthophoric
      within 6 months without surgery.

PMID- 7719083
TI  - [Systemic perfusion times in non-arteritic anterior ischemic optic neuropathy].
AB  - The pathogenesis of non-arteritic anterior ischemic optic neuropathy (AION) is
      not well understood. Local factors like elevated IOP or a low C/D ratio may play
      a role, as may systemic arteriosclerosis or reduced perfusion pressure. Reduced
      cardiac output may also contribute to the pathogenesis of the disease. We
      therefore investigated 17 healthy young persons, 9 patients with non-arteritic
      AION, and 10 age-matched controls using fluorescence perfusion scintigraphy, a
      technique that allows subclavia carotid time to be determined. Subclavia carotid
      time measures the circulation time of the heart and lung and is proportional to
      cardiac output. The mean subclavia carotid time of healthy young persons was 9.1
      +/- 1.6 s, 9.9 +/- 1.9 for AION patients, and 9.9 +/- 1.2 s for age-matched
      controls. The differences were statistically not significant. The correlation of
      perfusion times with blood pressure values showed, however, that systemic
      hypertension is accompanied by a relatively slow systemic perfusion time. In
      conclusion, it was not possible to demonstrate an absolutely reduced cardiac
      output in patients with non-arteritic AION during the day. Nevertheless, a drop
      in systemic blood pressure during the night may be responsible for a reduction in
      the blood supply to the optic nerve.

PMID- 7719084
TI  - [Correlation between clinical and molecular genetic findings in Leber's optic
      atrophy].
AB  - Leber's hereditary optic neuropathy (LHON) is associated with point mutations of
      mitochondrial DNA (mtDNA) that appear to be pathogenetic for this disease. These
      mutations affect nucleotide positions 3460, 4160, 11,778, 14,484, and possibly
      15,257. The pathogenetic significance of other mtDNA point mutations (secondary
      mutations) is less clear. We reviewed the clinical and molecular genetic
      characteristics of 29 visually symptomatic patients from 26 families. In
      addition, we studied 54 relatives of the maternal line of these patients. Sixteen
      of them underwent clinical and molecular genetic examination; 38 underwent only
      molecular genetic examination. The 29 affected individuals showed a male
      predominance of 93.1% (27/29) and ages of onset of visual loss ranging from 15 to
      55 years. The time interval between affected eyes was never longer than 1 year.
      Tobacco and/or alcohol abuse was common. Peripapillary microangiopathy was found
      in 20.7% (6/29) of our patients. The number of patients with peripapillary
      microangiopathy seems to be small, but we could not examine all patients early
      after onset of the disease: the time of first examination is critical for the
      diagnosis of peripapillary microangiopathy. From the 16 relatives who underwent
      clinical examination, 62.5% (10/16) also had peripapillary microangiopathy.
      Eighteen patients were analyzed by brain computed tomography or magnetic
      resonance imaging. Four definitely pathological results seem remarkably high in
      comparison with the results of other authors. Our LHON patients and their
      relatives invariably had an identical pattern of point mutations, both primary as
      well as secondary. Of the LHON patients, 79.3% had the primary mutation at
      position 11,778, 20.7% at position 3460. Different numbers and combinations of
      secondary mutations were observed in a large portion of both groups. Three
      patients with the 11,778 mutation noticed remarkable visual recovery. There was
      no clear correlation between the type and number of point mutations in the
      individual and the severity of the disease.

PMID- 7719085
TI  - [Driving with light during the day?].
AB  - In various Scandinavian countries the use of headlights during daytime (daytime
      running light DRL) is obligatory since many years. In Canada all new cars have to
      be equipped with a daytime running light since 1990. Whether or not in Germany or
      in the southern neighbouring countries a daytime running light should be used is
      matter of controversial discussion during the least years. Daytime running light
      increases the visibility of oncoming cars tremendously. Not only the drivers, but
      also pedestrians and cyclists profit from this gain of visibility. Especially
      drivers with poor vision, who will become more and more frequent during the
      coming years due to the increase of percentage of older drivers, have a specific
      profit from daytime running light. Potentially negative side-effects of daytime
      running light are: reduction of visibility of the brake-lights, glare, loss of
      visibility for pedestrians and cyclists, damage to the retina, increase of fuel
      consumption. All these arguments are either not crucial or cannot be documented
      by statistical data. On the other hand the data which are available up to now
      concerning frequency of accidents in those countries and areas in which daytime
      running light was used or is used, show a trend, sometimes even a statistical
      significant reduction of daytime accidents. This reduction is especially
      pronounced for accidents with pedestrians and cyclists. Overall, there are more
      and better arguments for using daytime running light, also in Germany. A
      technical alternative would be an automatic switching of the headlights if
      horizontal illuminance drops below a specific limit, e.g. 2000-3000 lx. Such an
      automatic procedure would increase the percentage of cars using headlights in
      critical situations during daytime.

PMID- 7719086
TI  - [Clinical and experimental studies on analgesic effects of ipsilateral and
      contralateral stimulations with electro-acupuncture].
AB  - Through the treatment of 65 cases of painful diseases with electroacupuncture, in
      comparing with the analgesic effect of contralateral stimulation (CS) and
      ipsilateral stimulation (IS), it was verified that IS and CS had the similar
      effect on pain-relieving, while CS was better in improving motor impairment. By
      testing the rat's pain threshold and recording the neuronal activity in the D
      PAG, it was found that neither IS nor CS could increase the pain threshold in the
      unilateral D-PAG lesioned rats, and the excited neuronal discharge was recorded
      in the unilateral D-PAG by stimulating rat's Zusanli (ST 36) at each side. It
      indicates that IS and CS might share the same high level afferent pathway in
      acupuncture analgesia in CNS.

PMID- 7719087
TI  - [Conservative therapy of combining laparoscopy and Chinese medicine for ectopic
      pregnancy].
AB  - 44 cases of ectopic pregnancy have been treated conservatively by combining
      laparoscopy with TCM and all were successful. After confirmatory diagnosis was
      made under laparoscope low dose (5-15mg) of Methotrexate (MTX) was injected into
      tubal swelling, as well as taking modified Huo-Luo-Xiao-Ling Dan orally and using
      Ding-Tong paste and Zi-Gong pill externally, it not only improved the function of
      herbal medicine that was not potent enough to kill active embryo, but also gave
      full play of TCM which could remove stasis and masses by promoting blood
      circulation to assist in killing the embryo. The successful rate (100%) of
      combined therapy was significantly higher than that (78.2%) of control group
      (using TCM only, P < 0.01). Comparing with the two groups in successful cases,
      the mean serum hCG concentrations per day of combined therapy lowered faster than
      that of control group (P < 0.005), the mean time of abdominal pain disappearance
      and hospitalized period of combined group were shorter (P < 0.01). In a word,
      this combined therapy is a simple and safe method which could preserve
      reproductive function to the maximum.

PMID- 7719088
TI  - [Clinical study on repeated infantile respiratory tract infection treated by
      kanggan zhibao oral liquor].
AB  - The clinical observation of repeated infantile respiratory tract infection
      treated by Kanggan Zhibao (KGZB) oral liquor and controlled with levomisole was
      studied. The results showed that the total effective rate of KGZB was 93.2%,
      which was significantly more effective than that of the control group (P < 0.05).
      In relieving symptoms and signs, KGZB was also superior to the control group (P <
      0.05). Both the KGZB and the levomisole could enhance and modulate the immunity
      function of T-lymphocyte and they could increase RBC-C3b receptor rosette
      formation rate, so that it had no significant difference in comparing with the
      healthy group (P > 0.05). It suggested that the therapeutic mechanism was related
      to this.

PMID- 7719090
TI  - [Relationship between local effect of cortisol used by chronic bronchitis
      patients and syndrome differentiation in TCM].
AB  - Serum cortisol levels and bronchoalveolar lavage fluid (BALF) from 105 patients
      with chronic obstructive pulmonary disease (COPD) and 36 normal subjects were
      examined and the relationship between cortisol inhibiting the TXB2 secreted by
      alveolar macrophage (AM) and the theory of Syndrome Differentiation in TCM was
      explored. Results showed: (1) No significant differences were found between
      chronic bronchitis and normal subjects on cortisol levels in serum, but in BALF,
      cortisol levels was significantly lower in Lung Qi Deficiency when compared with
      that in normal subjects. (2) the levels of cortisol inhibiting the TXB2 secreted
      by AM which were significantly lower in chronic bronchitis when compared with
      that in control. In short, the amount and function of cortisol in BALF were
      significantly different in various syndromes in TCM of chronic bronchitis.

PMID- 7719089
TI  - [Effect of xiaoyu pian on new platelet aggregation defect].
AB  - The Xiaoyu pian (XYP, mainly consisted of prunus persica, Carthamus tinctorius,
      Glycyrrhiza uralensis, etc) was used to treat patients with new platelet
      aggregation defect. Patients were divided into 2 groups, the TCM group (72 cases)
      treated with XYP and the control group (65 cases) treated with vitamin C and P
      and/or adrenosem for at least 3 months. The results showed that marked effective
      rate was 87.5% in TCM group and 35.4% in control group (chi 2 = 39.7, P < 0.01);
      the recovery rate of platelet was 91.8% in the former and 10.3% in the latter
      (chi 2 = 71.4, P < 0.01); the recurrence rate of follow-up (6 months after
      treatment) was 30.8% in the former and 82.1% in the latter (chi 2 = 19.2, P <
      0.01). The difference between two groups was very significant. The results
      suggested that XYP could regulate the hemostatic action and the platelet
      aggregation function. It is worthwhile to use XYP as an hemostatic clinically.

PMID- 7719091
TI  - [Intraperitoneal perfusion of compound injection of salvia miltiorrhiza with
      dachengqi decoction in treating adhesive intestinal obstruction].
AB  - 47 cases of adhesive intestinal obstruction after decompression operation were
      treated with intraperitoneal perfusion of compound injection of Salvia
      Miltiorrhizam intraperitoneally before closing the abdominal cavity and Dachengqi
      decoction oral given post-operatively. Follow up study for 2-9 years showed the
      effective rate was 100% except one case died of other unrelevant disease. Another
      38 cases of the same disease and same operation procedure were selected as the
      control group, which were given antibiotics intraperitoneally before closing the
      abdominal cavity. The effective rate was 73.38%. The result in the therapeutic
      group was significantly better than that in the control group (P < 0.01).

PMID- 7719092
TI  - [Intervention of lidocaine and Astragalus membranaceus on ventricular late
      potentials].
AB  - 16 and 22 patients with positive ventricular late potentials (LP) recorded on
      signal-averaged electrocardiograms (SAECG) were treated with lidocaine 100 mg iv.
      or Astragalus membranaceus 24 g iv. drip for 2 weeks respectively. As a result,
      the SAECGs of 2 (12.5%) and 3 (13.6%) of them normalized respectively. Compared
      with baseline, there were no significant changes in average HFQRSD, LAS and RMS
      40 after treatment of lidocaine. HFQRSD and LAS were shortened significantly
      115.9 +/- 29.9 vs 125.1 +/- 29.4 ms (P < 0.001); and 44.8 +/- 15.4 vs 52.8 +/-
      15.4 ms (P < 0.001), and RMS 40 was enlarged 20.0 +/- 18.6 vs 12.8 +/- 19.0
      microV (P < 0.05) only after treatment of Astragalus membranaceus. It is
      suggested that the duration of LP was shortened.

PMID- 7719093
TI  - [Immunological observation on chyluric patients with heat-clearing and hemostatic
      drugs].
AB  - In order to investigate the pathogenesis and therapeutic mechanism of chyluria,
      an experiment with a basic Heat-clearing and hemostatic prescription was
      conducted in treating 30 patients of chyluria. The result, 26 cases were cured
      completely. The cell-mediated and humoral immunity observation showed that OKT3
      and OKT4 levels were commonly low in chyluric cases, and OKT8 as higher than
      normal value, the OKT4/OKT8 ratio was inverted before treatment. While OKT3 and
      OKT4 increased commonly, and OKT8 decreased with the OKT4/OKT8 ratio adjusted
      after treatment. Meanwhile, humoral immunity level was also commonly low before
      treatment, it increased after treatment.

PMID- 7719094
TI  - [Effect of jiutuo II injection on shock model of superior mesenteric artery
      occlusion in rabbit].
AB  - Tang's SMAO method was adopted to produce shock model to observe the efficacy of
      the Jiutuo II(JTII) intravenously given. It was found that JTII could normalize
      the BP rapidly, which were superior to that of Dopamine and NS groups (P < 0.05,
      P < 0.01). At the same time, it could decrease mortality rate, comparing with
      Dopamine and NS the difference was significant (P < 0.05, P < 0.01); and it could
      also inhibit the formation of lipid peroxides (LPO). The contents of LPO in
      heart, liver, kidney of shock rabbit were obviously lower than that of Dopamine
      and NS groups (P < 0.05, P < 0.01). The electron microscopy indicated that the
      drug could relieve the injury of mitochondria and lysosome in the tissues of
      heart, liver and kidney and protect the cellular ultrastructure of cardinal
      viscera. This study suggests that the JTII had good efficacy in treating the
      shock rabbit caused by SMAO method.

PMID- 7719095
TI  - [Effect of tetramethylpyrazine in inhibiting respiratory burst of
      polymorphonuclears and scavenging oxygen free radicals].
AB  - Chemiluminescence method was used to measure (1) Active oxygen production induced
      by respiratory burst of polymorphonuclears (PMN) from human blood stimulated with
      phorbol myristate acetate (PMA); (2) Superoxide (O2-.) induced by xanthine
      xanthine oxidase system; (3) Hydroxyl radicals (.OH) produced by Vit C-Cu(2+)
      zymosan; and (4) The release of hydrogen peroxide (H2O2). Effects of
      tetramethylpyrazine on these active oxygen species were observed. The results
      showed respiratory burst of PMN was inhibited by tetramethylpyrazine, superoxide
      and hydrogen peroxide were scavenged by tetramethylpyrazine and their median
      inhibition concentration (IC50, mumol.L-1) were 5.6 and 7.1 respectively.

PMID- 7719096
TI  - [Experimental study on effect of Brucea javanica oil emulsion on rabbit
      intracranial pressure].
AB  - Using the method of intubation into lateral cerebral ventricle, the effect of
      Brucea javanica oil emulsion (BJOE) venous emulsion and oral emulsion on rabbits
      with normal and intracranial hypertension respectively were observed, to study
      whether BJOE could reduce intracranial pressure or not. The results shown that
      venous emulsion of BJOE had strong action against the elevation of intracranial
      pressure produced by SNP (P < 0.01) while oral emulsion had mild action against
      it, which was similar to the clinical observation exhibiting improvement of
      clinical manifestations after application of BJOE on intracranial hypertension
      caused by brain metastasis from lung cancer.

PMID- 7719097
TI  - [Studies on hypoglycemic effect of xuetangping].
AB  - Effects of xuetangping (XTP) on serum sugar liver glycongen in diabetic rats
      induced by alloxan were studied. The result showed that XTP (1.5 g/kg qd 14 d)
      lowered serum sugar near normal level in diabetic rats. While at 14d, XTP also
      increased the content of liver glycogen in diabetic rats and reduced the
      mortality of it XTP (0.75 g/kg ig qd 7d) prevented the alloxan induced elevation
      of serum sugar level in rats.

PMID- 7719098
TI  - [Evaluation of traditional Chinese medicine influence to the quality of life of
      patients with malignant tumors].

PMID- 7719099
TI  - [Recent progress in the study on Chinese traditional lipid regulating drugs].

PMID- 7719101
TI  - [Effect of electroacupuncture on gastric acid secretion and gut hormones].
AB  - 21 patients with mild type of chronic superficial gastritis were selected in this
      study. The effect of electroacupuncture in Zhongwan (RM12), Neiguan (P6) and
      Sanyinjiao (Sp6) on gastric acid secretion, serum gastrin, plasma somatostatin,
      plasma motilin concentration and erythrocyte acetylcholinesterase (AchE) activity
      were observed. The results were as follows: There were significant decreases in
      gastric acid output, serum gastrin concentration and AchE activity (P < 0.05),
      but no significant changes in plasma somatostatin and motilin concentration (P >
      0.05) after simultaneous electroacupuncture in Zhongwan, Neiguan and Sanyinjiao.

PMID- 7719100
TI  - [Progress in pharmacology and clinical application of Ligusticum wallichii].

PMID- 7719102
TI  - [Effect of sheng mai san on lipid peroxidation in acute myocardial infarction
      patients].
AB  - The effect of Sheng Mai San (SMS) on the coronary heart disease (CHD) patients
      (30 angina pectoris and 68 acute myocardial infarction, AMI) and its peroxidation
      damage was studied. It was shown that the activities of superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-Px) in blood were decreased and the content
      of malondialdehyde (MDA) in plasma was increased in CHD patients in comparison
      with the healthy controls (P < 0.001). When SMS was orally administered in 38 AMI
      patients, both SOD and GSH-Px activities were increased and the level of MDA
      decreased (P < 0.05), and these changes were even more significant when SMS was
      further ingested for another two weeks (P < 0.001). At the same time, it was
      found that the changes of SOD, GSH-Px and MDA in the control group (30 AMI
      patients not taking SMS) were not significantly different (P > 0.05). It could be
      assumed that the pathogenesis of CHD is associated with free radical (FR)
      triggering a chain reaction of the lipid peroxidation, and that SMS is acting as
      an effective free radical scavenger, which would ameliorate the lipid
      peroxidation damage. Thus, SMS could be administered in the prevention and the
      treatment of CHD.

PMID- 7719103
TI  - [Clinical study on Helicobacter pylori infected chronic gastritis treated with
      supplementing qi and promoting blood circulation drugs].
AB  - The syndrome of Qi Deficiency and Blood Stasis of chronic gastritis infected by
      Helicobacter Pylori (HP) was treated with the principle of supplementing Qi and
      promoting blood circulation. The clinical symptoms, inhibiting and killing of HP
      and pathohistological study have been observed. It was proved that the treatment
      could improve the clinical symptoms, reduce the infiltration of inflammatory
      cells and ameliorate the hyperemia and edema of gastric mucosa. Its inhibition
      and killing of HP was similar to the gentamycin sulfate (P > 0.05). Toxic and
      side effects have not been observed by taking this remedy.

PMID- 7719104
TI  - [Effect of berberine on transit time of human small intestine].
AB  - Sorbitol was used as a test sugar for the determination of small intestinal
      transit time (SITT) by means of breath hydrogen test (BHT). After oral
      administration of 15g sorbitol, breath hydrogen increased markedly (delta H2 > 5
      mumol/L) in 26 of 30 subjects. Following ingestion of a mixture of meglucamine
      diatrizoate and sorbitol by 18 subjects, SITT measured by BHT correlated closely
      with the simultaneously determined time for the meglucamine diatrizoate in
      reaching ileo-cecum. The BHT was used to investigate the effect of berberine on
      SITT in human. SITT in 20 healthy subjects was 71.10 +/- 22.04 min, SITT was
      significantly delayed to 98.25 +/- 29.03 min after oral administration of the
      1.2g of berberine (P < 0.01). This result suggested that the antidiarrheal
      property of berberine might be mediated, at least in part, by its ability to
      delay the small intestinal transit.

PMID- 7719105
TI  - [Epidemiological study of blood stasis and plasma tissue plasminogen activator
      and its inhibitor activity in healthy aged].
AB  - According to the blood stasis survey of 77 healthy subjects in presenile
      geriatric period, in comparison with 35 healthy young people, it was found the
      51.79% of healthy subjects had blood stasis. The detectable rate were
      significantly different among various age groups (P < 0.005), and the rate
      increase was age-dependent. Chromogenic peptide substrate analytical method was
      used to detect plasma tissue plasminogen activator (t-PA), tissue plasminogen
      activator inhibitor (PAI) activity and ratio of P/t. The result revealed that the
      activity of plasma t-PA in presenile geriatric period subjects was significantly
      higher than that of young people (P < 0.01), but the activity of PAI had no
      difference in various age groups, and the ratio of P/t was markedly decreased. It
      showed that this was the physiological compensatory reaction of aging organism
      against hypercoagulability, and it was an effective way to maintain the
      physiological balance of the aged.

PMID- 7719106
TI  - [Study on advanced non-small cell lung cancer patients with Qi deficiency and
      blood stasis syndrome].
AB  - 108 cases of advanced non-small cell lung cancer (NSCLC) with Qi deficiency and
      blood stasis syndrome (QDBS) had been studied in this paper. It has been found
      that: (1) QDBS existed commonly in 60.2% of NSCLC patients. (2) QDBS patients had
      lowered immune function and blood hypercoagulating function, as compared with
      healthy persons. (3) The abnormal change of immunological indexes such as TC
      subgroup. TXB2, 6-keto-PGF1 alpha, fibrinogen and plasmin activity as well as
      hemorheological indices are important pathophysiological manifestation of QDBS.
      Thus, the principle of supplementing Qi and activating blood circulation combined
      with reducing phlegm and resolving masses should be emphasized in future
      research.

PMID- 7719107
TI  - [Treatment of 36 corticosteroid-dependent type of aspirin asthma patients with
      Glucosidorum Tripterygii totorum].
AB  - This paper reports that substitution of Glucosidorum Tripterygii Totorum (GTT)
      for cortical hormone used to treat corticosteroid-dependent type of aspirin
      asthma, 60 mg, 3 times a day. The result showed that total effective rate was
      100% including 31 cases of marked effective (86.11%) and 5 cases of effective
      (13.89%). Corticosteroid in the blood was significantly elevated to normal level
      after treatment (P < 0.001), Cushing's syndrome was cleared up gradually. The
      blood glucose in 9 cases complicated with diabetes mellitus was recovered and
      glucosuria test was negative. The value of peak expiratory flow (PEF) was
      increased to some extent (P of male < 0.01, of female < 0.05), especially on
      those not complicated with emphysema. There was no side-effect during the
      treatment and could avoid the side-effect of cortical hormone. This therapy was
      valuable.

PMID- 7719108
TI  - [Study of treatment on acquired infantile mental retardation with traditional
      Chinese and Western medicine].
AB  - 80 cases with acquired infantile mental retardation caused by perinatal brain
      injury was treated with large doses of hyoscyamus, self made Retarded Recovery
      Pill and acupuncture. At the same time, 50 cases were taken as control group
      treated with Nao An Tai, Nao Fu Kang, etc. After 3 month treatment, the
      Intelligence Quotient (IQ) increased by 15 points in 29 cases of treatment group,
      while 3 cases in control group, chi 2 = 15.2, P < 0.01. After treatment for 6
      month the IQ increased in 41 and 5 cases respectively, t = 5.53, P < 0.01. In
      58.75% of the faculty of speech and motion greatly improved. It revealed that to
      treat the acquired infantile mental retardation, the combined therapy of
      traditional Chinese and Western medicine is effective.

PMID- 7719109
TI  - [Effect of kidney tonifying herbs on morphological changes of adrenal cortex in
      androgen-sterilized rats].
AB  - Young rats of 9-day old with testosterone propionate subcutaneously injected were
      used as an androgen sterilized rats (ASR) model. On 80th day, herbal extract of
      tonifying the Kidney was fed for 14 days, all animals were sacrificed by cardiac
      perfusion method on 100 days of ages. Morphological studies with light and
      electron microscope, immunohistochemical studies with argyrophilic nucleolar
      organiser region (AgNOR) and proliferating cell nucleolar antigen (PCNA) were
      used for observations on the morphological change of adrenal cortex. In control
      group (treated with testosterone propionate only) the reticular zone of the
      adrenal cortex extented widely in which cellular fatty drops, AgNOR and PCNA
      increased apparently. In animal treated with herbs, the width of the reticular
      zone, the numbers of AgNOR and PCNA reduced significantly to normal levels (P <
      0.01, P < 0.01, P < 0.01) and numbers of fatty drops also decreased. It suggests
      that during inducing ovulation in ASR tonifying Kidney herbs simultaneously
      regulated the adrenal function besides the chief function on pituitary-ovary
      regulation.

PMID- 7719110
TI  - [Effects of acupuncture on blood pressure, SOD,LPO and five kinds of trace
      elements to stenosis of renal artery caused hypertension in rats].
AB  - Changes of blood pressure, superoxide dismutase (SOD), lipid peroxidation (LPO)
      and concentration of five kinds of trace elements including Cu, Zn, Fe, Ca, Mg
      were observed before or after acupuncture treatment in the stenosis of renal
      artery caused hypertension in rats [correction of mice]. It was demonstrated that
      acupuncture in the points of Zusanli, Neiguan, Sanyinjiao and Yongquan in mice
      could reduce the blood pressure significantly and influence the concentrations of
      SOD, LPO and five kinds of trace elements in the stenosis of renal artery caused
      hypertension in mice. The possible mechanisms of acupuncture in reducing the
      blood pressure and influencing the changes of SOD, LPO and five kinds of trace
      elements were also discussed.

PMID- 7719111
TI  - [Effect on academic thought of integrated traditional Chinese medicine and
      Western medicine].

PMID- 7719112
TI  - [Progress of traditional Chinese medicine treatment on infantile pneumonia].

PMID- 7719113
TI  - [Ultrasonic diagnosis '94. Three-country meeting, Basel, 26-29 October 1994.
      Abstracts].

PMID- 7719114
TI  - Overview of toxicological data on rifabutin.
AB  - Rifabutin is a wide spectrum antibiotic particularly active on atypical and
      rifampicin-resistant mycobacteria. Rifabutin is more potent than rifampicin on
      Mycobacterium tuberculosis in vitro. Its mode of action is characterized by a
      high intracellular penetration in treated individuals. Clinical trials have
      proven the therapeutic value of rifabutin especially in AIDS patients with
      concomitant MAC. The preclinical safety evaluation of this compound included
      single and repeated dose toxicity studies of up to one year in rodents and non
      rodents, reproduction and carcinogenicity studies and mutagenicity tests. During
      toxicological studies the most significant finding after repeated administration
      of rifabutin was the presence of multinucleated hepatocytes (MNH) in rats. This
      is a species specific finding which did not affect the life span of the
      hepatocytes. As shown in carcinogenicity studies, there was no tendency to
      further proliferative changes. Another specific histological feature among the
      species studied was the presence of a lipofuscin-like brown pigment, which was
      seen in many organs. This is a common finding with amphipilic compounds, such as
      rifabutin, which bind lipids and proteins, forming membrane-bound complexes. Even
      in carcinogenicity studies this change did not constitute a stimulus to cell
      proliferation and did not cause any secondary changes. In rodents, there was a
      mild hemolytic anemia at doses higher than 10 mg/kg/day. At doses ranging from
      160-200 mg/kg/day rifabutin inhibited the functions of the male gonads in rats.
      This effect was reflected in a reduction of implantations observed in the
      fertility studies. Doses of 40 mg/kg/day did not induce any embryotoxic effects
      or changes in reproductive performance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719115
TI  - Lewis rats of the inbred strain LEW/Han: life expectancy, spectrum and incidence
      of spontaneous neoplasms.
AB  - Although Lewis rats are frequently used in biomedical research, little is known
      about their life-data and spontaneous pathology. Therefore, it was the aim of
      this study to determine the life expectancy, spectrum and incidence of
      spontaneous neoplasms of the inbred rat strain LEW/Han. A total of 629 LEW/Han
      rats (305 females and 324 males) from a specified pathogen-free breeding colony
      were kept from weaning up to their natural death under defined environmental
      conditions. A complete histological examination was performed on all organs and
      macroscopically altered tissues of all animals which died during the first three
      years of the study. These were 296 female (98%) and 213 male (66%) rats. The mean
      lifespan of the females (27.7 +/- 5.1 months) was significantly shorter than that
      of the males (32.5 +/- 6.6 months). In both sexes, the lifespan was mainly
      determined by the occurrence of neoplasms. Of the large spectrum of 52
      histologically different tumour types, the highest incidences were observed for
      adenomas of the pituitary gland and adenomas/adenocarcinomas of the adrenal
      cortex in both sexes, mammary gland tumours and endometrial carcinomas in
      females, and C-cell adenomas/adenocarcinomas of the thyroid gland and tumours of
      the haemopoietic system in males. Of these, the high incidences of tumours of the
      haemopoietic system in males (27.7%) and of endometrial carcinomas in females
      (45.2%) should be considered as characteristic features of the strain.

PMID- 7719116
TI  - Determination of epidermal proliferative activity in experimental mouse tail test
      by AgNOR analysis.
AB  - Nucleolar organizer regions are segments of DNA coding ribosomal genes, which can
      be histologically detected by silver technique as so-called AgNORs. The
      estimation of AgNOR number and AgNOR size are currently under investigation as
      markers of cellular proliferation activity. We therefore examined the epidermal
      AgNOR expression after topical application of different antiproliferative
      compounds using the mouse tail test. The epidermis of 0.025% fluocinolone
      acetonide-treated mouse tails had the lowest AgNOR expression. Pretreatment with
      0.2% Anthralin, 1% propyl gallate and 2% 3,4-hexaalkylbenzoylacrylic acid, an
      experimental phospholipase-A2 inhibitor, also revealed significant inhibition
      effects of epidermal AgNOR expression. Native and petrolatum-treated epidermis as
      control showed the highest AgNOR expression. The AgNOR results in basal cells
      proved to be more informative than these in the stratum spinosum, the best
      parameter was the AgNOR number. The obtained results were closely related to the
      values of the corresponding studies of PCNA expression. The AgNOR method seems to
      be useful for estimation of antiproliferative efficiency of pharmacological
      substances. This technique is simple in handling and can be applied using
      paraffin-embedded tissue sections.

PMID- 7719117
TI  - Histological and ultrastructural changes in the rat brain following systemic
      administration of picolinic acid.
AB  - Picolinic acid was administered intraperitoneally in a dose of 30, 60, or 100
      mmol, once every 24 h for 8 days. Histologically, under normal conditions as well
      as when picolinic acid was administered in a dose of 30 mmol the brain formations
      exhibited characteristic features. When picolinic acid was administered in a dose
      of 60 mmol or 100 mmol, the alterations were profound and developed selectively
      in hippocampus, being much less intense in the substantia nigra and striatum. In
      such cases, injuries of neuronal cell bodies were accompanied by symptoms of
      spongiosis. Within the hippocampus, the neuronal cell body injury was selectively
      restricted to the hilar and CA3 regions of stratum pyramidale. Tissue spongiosis
      was more intense at the granular layer, particularly within the hilus and in the
      mossy fiber area at CA3. Histochemically, a variable intensity of the reaction of
      succinic and alpha-glycerophosphate dehydrogenases was demonstrated. A decrease
      in their activities was observed in areas where the neuronal cell body injuries
      and spongiosis took place. No changes in the Ca-ATP-ase activity in brain
      formation after picolinic acid treatment were observed. Ultrastructurally, the
      changes within substantia nigra were manifested by neuronal cell bodies of the
      dark type and dendritic degenerations. Also less damaged neuronal cell bodies
      were seen. They were swollen, depleted of polyribosomes with dilated elements of
      RER and altered mitochondria. Some of the dendritic profiles were swollen with
      lucent cytoplasm. Most of the boutons in synaptic contact zones were unchanged.
      Most presynaptic terminals which were in junction with dark dendrites were
      swollen with or without crystal-like aggregates of synaptic vesicles.

PMID- 7719118
TI  - Investigations on the acute effects of neuropeptides on the pituitary
      adrenocortical function in normal and cold-stressed rats. I. Bombesin and
      neuromedin B.
AB  - The effects of a subcutaneous bolus injection of 2 micrograms bombesin (BM) or
      neuromedin B (NMB) on the function of the hypothalamo-pituitary-adrenocortical
      (HPA) axis were investigated in both normal and cold-stressed rats. The blood
      concentrations of ACTH, corticosterone (B) and aldosterone (ALDO) were measured
      by specific radioimmunoassays 1, 2 or 4 h after the neuropeptide administration.
      Cold stress strikingly enhanced plasma levels of ACTH, B and ALDO, and these
      rises lasted unchanged until 4 h. BM and NMB significantly elevated plasma
      concentrations of ACTH and B in both normal and stressed animals. In both groups
      of rats the level of circulating ALDO was not apparently affected by
      neuropeptides. In light of these findings the following conclusions can be drawn:
      (i) BM and NMB acutely activate the HPA axis, probably by acting via the same
      receptor; (ii) the mechanism underlying this effect of BM and NMB is independent
      of that involved in the cold stress-induced activation of the HPA axis; and (iii)
      the well-known acute ALDO secretagogue effect of ACTH is probably counteracted by
      a direct inhibitory action of BM and NMB on adrenal zona glomerulosa.

PMID- 7719119
TI  - Role of neutrophils and platelets in the pathogenesis of focal hepatocellular
      necrosis in endotoxaemia.
AB  - To clarify whether neutrophils and platelets are implicated in the pathogenesis
      of focal hepatocellular necrosis in endotoxaemia, we examined the relationship
      between the changes in neutrophils and platelets in peripheral blood and the
      degree of focal hepatocellular necrosis and serum transaminase activity in rats
      after endotoxin injection. The number of neutrophils in the peripheral blood
      decreased rapidly during the first hour after endotoxin injection and then
      increased. This initial decrease might be caused by the adhesion of neutrophils
      to pulmonary capillary walls, and the subsequent increase might be caused by
      granulocyte colony-stimulating factor mediated by endotoxin. However, there was
      no relationship between the degree of focal hepatocellular necrosis and the
      number of neutrophils sticking to the walls of hepatic sinusoids or the changes
      in the neutrophil count in the peripheral blood. The number of platelets in the
      peripheral blood decreased rapidly after endotoxin injection. There was a
      statistically significant relationship between the number of platelets in the
      peripheral blood and the level of serum transaminase activity: the fewer the
      platelets, the more severe was focal hepatocellular necrosis. The present study
      suggests that rapid and extensive consumption of platelets, rather than
      neutrophils sticking to the sinusoidal walls, is involved in the pathogenesis of
      focal hepatocellular necrosis in endotoxaemia.

PMID- 7719120
TI  - Investigations on the acute effects of neuropeptides on the pituitary
      adrenocortical function in normal and cold-stressed rats. II. Neurotensin and
      neuromedin N.
AB  - The effects of a subcutaneous bolus injection of 2 micrograms neurotensin (NT) or
      neuromedin N (NMN) on the function of the hypothalamo-pituitary-adrenocortical
      axis were investigated in both normal and cold-stressed rats. The blood
      concentrations of ACTH, corticosterone (B) and aldosterone (ALDO) were measured
      by specific radioimmunoassays 1, 2 or 4 h after the neuropeptide administration.
      Cold stress enhanced plasma levels of ACTH, B and ALDO, and these rises lasted
      unchanged until 4 h. NT did not affect either basal or stress-stimulated plasma
      levels of ACTH and B, while it lowered the plasma ALDO concentration at 4 h in
      normal rats and increased it at 1 h in stressed animals. NMN did not change the
      basal plasma level of ACTH, but it did markedly raise blood levels of both B and
      ALDO; on the other hand, in cold-stressed rats NMN strongly depressed ACTH
      response and decreased B plasma concentration at 2 h, without evoking apparent
      changes in ALDO response. In light of these findings the following conclusions
      and hypotheses can be drawn and suggested: (i) NT and NMN, when administered at a
      relatively high dose, do not affect ACTH release in rats under basal conditions;
      (ii) NMN, but not NT, is able to prevent cold stress-induced stimulation of ACTH
      secretion, probably by inhibiting hypothalamic thermoregulatory centers; and
      (iii) NT and NMN exert direct adrenocortical antisecretagogue and secretagogue
      effects, respectively, which could explain the evident lack of correlation
      between the levels of circulating ACTH and the plasma concentrations of the main
      adrenal steroid hormones in both normal and stressed rats after neuropeptide
      administration.

PMID- 7719121
TI  - No effect of RU 486 (mifepristone) on hepatocellular tumorigenesis in
      orchiectomized male mice induced by 3'-methyl-4-dimethylaminoazobenzene.
AB  - Effects of RU 486 (mifepristone) on hepatocellular tumorigenesis in
      orchiectomized male mice induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me
      DAB) were investigated. Male mice that had been treated with 3'-Me-DAB neonatally
      were orchiectomized at one month of age, and injected daily with vehicle only or
      RU 486 at 0.2 or 0.4 mg/day thereafter. In the liver of orchiectomized males
      injected with vehicle only, adenomatous nodules developed at incidences of 16.2
      and 38.5% at 9 and 12 months of age, respectively, but no carcinomas developed at
      these ages. Injections of RU 486 at 0.2 or 0.4 mg/day neither affect incidences
      of adenomatous nodules in the liver, their numbers per mouse, and their areas,
      nor promote the development of carcinomas. The present results suggest that the
      long term administration of RU 486 has no effects on hepatocellular
      tumorigenesis.

PMID- 7719122
TI  - Subchronic application of humic acids and associated compounds provokes
      histological changes of goitre in the rat.
AB  - 1. Different preparations of humic acids, a pyrogallol oxydation product (PYROP)
      and resorcinol were administered to male and female rats with the drinking water
      for 8 to 14 weeks. 2. By histometrical evaluation of the thyroid glands, an
      increase of the mean epithelial cell height of follicular epithelial cells was
      established in the 0.1% humic acid groups, 0.1% PYROP group and the 0.004%
      resorcinol groups. Females seemed to be more sensitive than males. Additionally,
      in some experiments, a decrease of the mean follicular diameter was found, which
      was the result of newly formed little follicles. The changes must be considered
      as a precursor of goitre. 3. In one of the experiments, in which circulating
      thyroid hormones were investigated, the serum thyroxine level in the male 0.1%
      humic acid group and the free thyroxine index in the female 0.1% humic group were
      diminished as compared to the control groups.

PMID- 7719123
TI  - The effect of different prostaglandins on rat gastric mucosa. Scanning
      electronmicroscopic investigations.
AB  - According to the present investigations prostaglandins showed a specific
      morphologic effect on (rat) gastric mucosa. Namely: During their effect the
      foveolae of the mucosa have opened; - which is a convincing sign of mucus
      production. This phenomenon (i.e. the foveola-opening), showed a direct
      correlation with the cytoprotective (anti-ulcerogenic) effect of the investigated
      prostaglandins in the order of PG-I2 > PG-E1 > PG-F2 alpha > 6-keto-PG-F1 alpha.

PMID- 7719124
TI  - Protective influence of zinc against the deleterious effects of ethanol in
      postimplantation rat embryos in vivo.
AB  - Zinc is a cofactor for alcohol dehydrogenase, the ethanol metabolizing enzyme.
      Ethanol-induced zinc deficiency could decrease ethanol metabolism, resulting in
      an increase in circulating and tissue ethanol levels. This may cause retardation
      in embryonic growth and development. The influence of zinc supplementation on
      ethanol-induced embryopathy was studied by the simultaneous administration of
      ethanol and zinc to pregnant SD rats from gestational day 6 through 12. Ethanol
      was given in the form of a liquid diet and zinc was administered
      intraperitoneally. The ethanol group received the liquid ethanol diet, the
      ethanol+zinc group received the ethanol diet and zinc and the pair-fed control
      group was given an isocaloric control diet. Embryos were explanted from all
      groups on day 12 of gestation. Embryos of animals treated with ethanol alone
      exhibited a significantly higher rate of resorption and retarded embryonic growth
      and development compared to the pair-fed control group. The embryonic protein
      content, crown-rump length, the number of somites and embryonic morphological
      score were significantly reduced in the ethanol-treated group. In addition, serum
      zinc concentration also was lower. Compared to embryos from ethanol-treated
      animals, embryos from ethanol+zinc treated animals showed a significantly higher
      number of somites; cardiac development was more advanced and embryonic protein
      content was higher. These observations suggest that zinc supplementation of
      ethanol-treated pregnant rats may have some protective influence against the
      embryopathic effects of ethanol.

PMID- 7719125
TI  - Inhibitory effect of the human recombinant tumor necrosis factor on the growth of
      the Morris hepatoma in rats.
AB  - The effect of the human recombinant tumor necrosis factor alpha (h rec TNF-alpha)
      on the transplantable Morris hepatoma 5123 was studied in Buffalo rats. The
      cytokine was repeatedly administered intratumorly (i.t.) in a dose of 1.5 x 10(4)
      U once a day in a cycle of four and eight days. The control groups consisted of
      animals given saline i.t. The experiments revealed an inhibitory effect of the h
      rec TNF-alpha upon the growth of neoplastic tumors. The biometric parameters of
      the tumors indicated that the inhibition of the Morris hepatoma was most
      effective after eight repeated doses of TNF. After injections of TNF-alpha, the
      tumors presented extensive hemorrhagic necrosis, the regressive alterations being
      found mainly in the central and intermediate tumor zones. In the early phase of
      the tumor growth, neoplastic tissue necrosis prevailed, as well as hemorrhages
      within the necrotic masses, necrosis of the blood vessel walls and thrombi in
      their lumina. In the later period, numerous fibres of the fibrous tissue, richly
      vascularized, occurred in the peripheral and intermediate zones. Clusters of
      eosinophilic granulocytes and macrophages with apoptotic bodies in the cytoplasm
      were seen on the border of the necrotic foci.

PMID- 7719126
TI  - Sequence seeking and counter streams: a computational model for bidirectional
      information flow in the visual cortex.
AB  - A computational model is proposed for some general aspects of information flow in
      the visual cortex. The basic process, called "sequence seeking," is a search for
      a sequence of mappings, or transformations, linking source and target patterns.
      The process has two main characteristics: it is bidirectional, bottom-up as well
      as top-down, and it explores in parallel a large number of alternative sequences.
      This operation is performed in a "counter streams" structure, in which multiple
      sequences are explored along two complementary pathways, an ascending and a
      descending one, seeking to meet. A biological embodiment of this model in
      cortical circuitry is proposed. The model serves to account for known aspects of
      cortical interconnections and to derive new predictions.

PMID- 7719127
TI  - Glutamate-like immunoreactivity and fate of Cajal-Retzius cells in the murine
      cortex as identified with calretinin antibody.
AB  - Cortical layers VI to II develop between two layers of older neurons, the
      marginal and subplate zones, which are believed to have unique roles in cortical
      development. While subplate cells have been found essential for the establishment
      of thalamocortical relationships, the function of the marginal zone and in
      particular of the neurons of Cajal-Retzius has not been elucidated. Here we show
      that an antibody against the calcium-binding protein calretinin labels the
      population of Cajal-Retzius cells throughout their life in the murine cerebral
      cortex. In prenatal and early postnatal stages, Cajal-Retzius cells were found
      evenly distributed throughout the murine cerebral cortex. Cajal-Retzius-like
      neurons were also found in the developing hippocampus and dentate gyrus, which
      indicates that they may have a general function in cortical development. From P8
      onward Cajal-Retzius cells disappeared from the neocortex and hippocampus, at the
      same time as degenerating immunoreactive neurons were observed. Calretinin
      positive Cajal-Retzius cells were glutamate immunoreactive and their presumed
      axon terminals formed asymmetric synapses. These observations indicate that Cajal
      Retzius cells may provide a tonic excitatory input, essential for the maturation
      of cortical neurons. Furthermore, since neuronal migration has been shown to be
      dependent on glutamate receptors, we propose that Cajal-Retzius cells releasing
      glutamate may direct migrating neuroblasts toward the marginal lamina, therefore
      creating the "inside-out" sequence of cortical development.

PMID- 7719128
TI  - Developmental remodeling of primate visual cortical pathways.
AB  - The pre- and postnatal developmental changes of the cortical afferents to area 17
      were studied in the macaque monkey. Paired injections of the retrograde tracers
      fast blue and diamidino yellow were made in area 17. Quantitative techniques were
      used to examine the spatial patterns of labeling in three distinct locations of
      the extrastriate cortex that correspond to known visual areas. In the adult, each
      cortical region has a characteristic laminar distribution. In the fetus the
      proportion of supragranular layer neurons in all cortical regions was much higher
      than in the adult. The present study shows that despite the very high levels of
      labeled supragranular layer neurons, there is some early areal specialization so
      that the adult configuration does not emerge from a uniform distribution. The
      developmental decline in the proportion of labeled supragranular neurons is
      complete by 1 month after birth. Each injection of tracer gave rise in each
      cortical area to dense labeling in a restricted region (projection zone). Areal
      measurements of projection zones in the supra- and infragranular layers showed
      that the developmental decrease in the proportion of labeled supragranular layer
      neurons is accompanied by a relative change of the dimensions of supra- and
      infragranular projection zones: the supragranular projection zone in the fetus is
      larger than the infragranular projection zone and vice versa in the adult. In the
      fetus, the two projection zones corresponding to each of the two tracers overlap
      in the supragranular layers whereas they are largely separated in the
      infragranular layers. During development there is a progressive decrease in the
      overlap of the supragranular projection zones and an increase in the overlap in
      the infragranular layers. Again, the adult configuration is achieved 1 month
      after birth. This developmental inversion of the areal dimensions of the
      projection zones in supra- and infragranular layers is accompanied by a drastic
      decrease in the proportion of double-labeled neurons located in supragranular
      layers. These results clearly show that early in development, axonal projections
      to area V1 are modified in very different ways according to whether they
      originate from supra- or infragranular layers. This developmental process lasts
      for about 80 d. These findings show that in the primate there is a prolonged
      remodeling of axonal projections that is a highly characteristic feature of this
      species.

PMID- 7719129
TI  - Anatomical evidence for MT and additional cortical visual areas in humans.
AB  - We stained human visual cortex for myelin, cytochrome oxidase, and the monoclonal
      antibody CAT-301 in an attempt to demonstrate and map MT (V5) and other visual
      cortical areas in humans. Both flattened and unflattened cortical tissue was
      examined. A likely candidate for area MT (V5), which we refer to as MT, was
      demonstrated using all three stains. Myelin and CAT-301 labels for MT were
      demonstrated to be coincident by comparing results from the two stains in
      adjacent sections. In all three stains, MT was an oval area approximately 1.2 x
      2.0 cm, located 5-6 cm anterior and dorsal to the foveal V1-V2 border. The
      position and size of MT as defined by the present anatomy are consistent with MT
      (V5) as defined by functional measures in humans. In addition, flattened cortical
      tissue stained for cytochrome oxidase revealed a distinctive staining topography
      in several cortical areas, including areas V1, V2, MT, PX, and VX. Similar
      studies in flattened cortex of macaque and green monkeys demonstrated distinctive
      dark cytochrome oxidase staining in MT, PX, MTc, and V3.

PMID- 7719130
TI  - The ontogeny of human gyrification.
AB  - During development the human cortex changes from a smooth lissencephalic
      structure to one that is highly convoluted. Increases in the degree of cortical
      folding are associated with brain size only for the first part of brain growth;
      during the second half, differences in cortical folding match those of brain
      size, resulting in no change in the degree of folding. When the degree of
      cortical folding is studied as a function of age, a brief postnatal overshoot, an
      effect of brain size, is observed. The analysis suggests that the mechanical
      hypothesis of cortical buckling can best explain the degree of cortical folding,
      but that other hypotheses, like gyrogenesis, are required to explain the
      placement and orientation of sulci. The adult asymptote in degree of cortical
      folding is associated with the onset and disappearance of single subplate lamina,
      suggesting that subplate:cortical plate associations should be examined as causal
      for gyrification. Areas whose sulci differ in length between the two hemispheres
      have similar degrees of convolutedness, supporting interpretations that the sizes
      of gyri are asymmetric in the two hemispheres. The ontogenetic data support the
      thesis that human cortical proportions evolved when the brain enlarged in size
      and that the process was not one of neoteny.

PMID- 7719131
TI  - Basic fibroblast growth factor increases the number of excitatory neurons
      containing glutamate in the cerebral cortex.
AB  - Stem cells isolated from the ventricular zone of embryonic day 12.5 rat
      telencephalon progressively proliferate and differentiate in vitro into three
      major classes of amino acid-containing neurons, glutamate, aspartate, and GABA.
      We quantitatively examined the effect of basic fibroblast growth factor (bFGF)
      and nerve growth factor (NGF) on amino acid-containing neurons. bFGF caused a
      threefold increase in glutamate-containing neurons, while the number of GABA- and
      aspartate-containing neurons was not significantly changed. In contrast, NGF did
      not alter the number of amino acid-containing neurons. The ratio of glutamate- to
      GABA-containing neurons in untreated or NGF-treated cultures was 0.6:1. In the
      bFGF-treated cultures, this ratio was 1.4:1, which closely approximates the ratio
      in the cerebral cortex in vivo. Treatment with antisense oligonucleotides
      targeted to bFGF mRNA provoked a 50% decrease in the number of glutamate
      containing neurons but had no significant effect on the GABA-containing neurons.
      Thus, diffusible factors such as bFGF may play an important role in determining
      the relative proportion of excitatory versus inhibitory neurons in the cerebral
      cortex by selectively regulating the proliferation of stem cells committed to
      different neurotransmitter phenotypes.

PMID- 7719132
TI  - Visual memory, visual imagery, and visual recognition of large field patterns by
      the human brain: functional anatomy by positron emission tomography.
AB  - We measured the regional cerebral blood flow (rCBF) in 11 healthy volunteers with
      PET (positron emission tomography). The main purpose was to map the areas of the
      human brain that changed rCBF during (1) the storage, (2) retrieval from long
      term memory, and (3) recognition of complex visual geometrical patterns. A
      control measurement was done with subjects at rest. Perception and learning of
      the patterns increased rCBF in V1 and 17 cortical fields located in the cuneus,
      the lingual, fusiform, inferior temporal, occipital, and angular gyri, the
      precuneus, and the posterior part of superior parietal lobules. In addition, rCBF
      increased in the anterior hippocampus, anterior cingulate gyrus, and in several
      fields in the prefrontal cortex. Recognition of the patterns increased rCBF in 18
      identically located fields overlapping those activated in learning. In addition,
      recognition provoked differentially localized increases in the pulvinar,
      posterior hippocampus, and prefrontal cortex. Learning and recognition of the
      patterns thus activated identical visual regions, but different extravisual
      regions. A surprising finding was that the hippocampus was also active in
      recognition. Recall of the patterns from long-term memory was associated with
      rCBF increases in yet different fields in the prefrontal cortex, and the anterior
      cingulate cortex. In addition, the posterior inferior temporal lobe, the
      precuneus, the angular gyrus, and the posterior superior parietal lobule were
      activated, but not any spot within the occipital cortex. Activation of V1 or
      immediate visual association areas is not a prerequisite for visual imagery for
      the patterns. The only four fields activated in storage recall and recognition
      were those in the posterior inferior temporal lobe, the precuneus, the angular
      gyrus, and the posterior superior parietal lobule. These might be the storage
      sites for such visual patterns. If this is true, storage, retrieval, and
      recognition of complex visual patterns are mediated by higher-level visual areas.
      Thus, visual learning and recognition of the same patterns make use of identical
      visual areas, whereas retrieval of this material from the storage sites activates
      only a subset of the visual areas. The extravisual networks mediating storage,
      retrieval, and recognition differ, indicating that the ways by which the brain
      accesses the storage sites are different.

PMID- 7719133
TI  - Neuromuscular disorders: gene location.

PMID- 7719134
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 7719135
TI  - Exclusion of the candidate locus FSP1 in six families with late-onset autosomal
      dominant spastic paraplegia.
AB  - Hereditary spastic paraplegias are neurological hereditary conditions of unknown
      aetiology. In pure spastic paraplegia, most of the pedigrees display an autosomal
      dominant mode of inheritance. A gene for pure autosomal dominant spastic
      paraplegia (ADSP), termed FSP1, was mapped to chromosome 14q in a large pedigree
      with early-onset disease. This locus was tested by linkage analysis in six large
      French kindreds of ADSP with late-onset disease, using four microsatellites
      spanning a 9 cM interval including FSP1. FSP1 could be excluded in five of the
      six families, while no evidence for linkage was found in the remaining family.
      These results suggest that FSP1 is not involved in late onset ADSP, at least in
      the six families studied.

PMID- 7719136
TI  - Exclusion of the gene locus for spinal muscular atrophy on chromosome 5q in a
      family with infantile olivopontocerebellar atrophy (OPCA) and anterior horn cell
      degeneration.
AB  - Two sisters with infantile OPCA plus spinal muscular atrophy (SMA) are reported.
      Both showed severe hypotonia and psychomotor delay from birth, and in addition,
      nystagmoid eye movements and vision impairment were evident. Cerebellar
      hypoplasia with cystic dilatation was seen by neuro-imaging methods.
      Pathoanatomically, a marked cerebellar hypoplasia and neuronal loss in the basal
      ganglia, brainstem and anterior horns were found in the deceased girl. Linkage
      studies with polymorphic markers of the region 5q11.2-q13.3 flanking the gene
      locus for infantile SMA showed identical parental haplotypes in the patients and
      their older healthy sister. It can be concluded that the gene locus for infantile
      SMA on chromosome 5q is not responsible for infantile OPCA plus anterior horn
      cell degeneration in the described family which might apply to this disorder in
      general.

PMID- 7719137
TI  - Olivopontocerebellar hypoplasia with anterior horn cell involvement (SMA) does
      not localize to chromosome 5q.

PMID- 7719138
TI  - Chaos in the classification of SMA: a possible resolution.

PMID- 7719139
TI  - Rimmed basophilic vacuoles and filamentous inclusions in neuromuscular disorders.
AB  - To study the incidence of rimmed basophilic vacuoles (RBV) and 15-21 nm
      filamentous inclusions in neuromuscular disorders, other than inclusion body
      myositis (IBM) and to determine the diagnostic value of RBV quantitation in the
      differential diagnosis of IBM, we reviewed 1600 muscle biopsies for RBV and 750
      biopsies for filamentous inclusions. The number of RBV-positive fibers per 10 mm2
      -the RBV-fiber density--was determined. The incidence of RBV in non-IBM biopsies
      was 8.8 per 1000. Major diagnostic categories were neurogenic disorders (n = 7)
      and limb girdle muscular dystrophies (LGMD) (n = 3). In IBM (n = 7) the RBV-fiber
      density ranged from 10.4 to 63.1 and was significantly higher than in neurogenic
      disorders (0.9-4.4) and LGMD (1.1-2.7). The highest value was found in rigid
      spine syndrome (205.8). Filamentous inclusions were seen in 2.7 per 1000 non-IBM
      biopsies, including familial oculopharyngeal muscular dystrophy with distal
      myopathy (OPMD-DM), rigid spine syndrome, acid maltase deficiency and amyloid
      neuropathy. RBV and filamentous inclusions coexisted in rigid spine syndrome and
      in familial OPMD-DM. RBV, as well as filamentous inclusions, has a very low
      incidence in non-IBM neuromuscular disorders; the RBV-fiber density may help to
      discriminate neurogenic disorders and LGMD from IBM.

PMID- 7719140
TI  - Diabetic muscle infarction: a new perspective on pathogenesis and management.
AB  - Two patients with insulin dependent diabetes mellitus developed recurrent
      episodes of focal muscle pain and swelling. Clinical evaluation, magnetic
      resonance imaging (MRI) and muscle biopsy confirmed the diagnosis of recurrent
      hemorrhagic muscle infarctions. Our studies suggest that muscle infarction
      occurred because of hypercoagulability and associated vascular endothelial
      damage. Based on these findings we recommend long-term anticoagulation to prevent
      recurrent infarction.

PMID- 7719141
TI  - Experimental thyrotoxic myopathy: radioautography of protein synthesis in
      skeletal muscle and motor neurons of spinal cord.
AB  - The total protein synthesis was studied in skeletal muscle and spinal motor
      neurons in experimental thyrotoxic myopathy (TM) mice by using radioautography
      with 3H-methionine. A significant increase of mean specific radioactivity was
      found in motor neurons of mice with TM. No statistical differences were
      established in the level of 3H-methionine inclusions into muscle fibre proteins
      of experimental and control animals. Thus, the total protein synthesis in motor
      neurons is significantly increased with TM, while there is no change in the
      skeletal muscle. Our data suggest that muscular weakness in TM is not the
      consequence of protein metabolism disorders in skeletal muscle fibres.

PMID- 7719142
TI  - Malignant hyperthermia in a patient with Becker muscular dystrophy: dystrophin
      analysis and caffeine contracture study.
AB  - We present a 17-year-old boy with Becker muscular dystrophy (BMD) who developed
      hyperthermia and heart failure after general anesthesia. He presented clinical
      features of malignant hyperthermia (MH), and had masseter spasm and elevated body
      temperature (38.7 degrees C) with very high serum CK activity (107,000 IUl-1).
      Dystrophin tests confirmed a clinical diagnosis of BMD in the patient, i.e. faint
      and patchy immunostaining pattern of skeletal muscle, truncated dystrophin
      protein and a deletion of exons 3 and 4 of the dystrophin gene. To inquire into
      the mechanism of MH associated in the patient, we tested caffeine contracture
      reaction by the skinned fiber method. We found an increased sensitivity to
      caffeine only in type 1 muscle fibers. The rate of Ca(2+)-induced Ca2+ release
      (CICR) was normal, suggesting that the mechanism of "MH" observed in our patient
      with BMD is not the same as that of classical MH. A possible mechanism might be
      related to derangements of the sarcoplasmic reticulum membrane in BMD, which
      sensitize the membrane to caffeine or other agents.

PMID- 7719143
TI  - Recurrent congenital arthrogryposis leading to a diagnosis of myasthenia gravis
      in an initially asymptomatic mother.
AB  - We report a sibship in which the syndrome of congenital arthrogryposis occurred
      in two male and two female neonates, three of whom died. The mother was
      asymptomatic at the time of the first pregnancy and the subsequent development of
      muscle weakness was later confirmed to be due to myasthenia gravis. The
      literature on this association is briefly reviewed and the extremely high risk of
      recurrence of this complication in subsequent pregnancies is addressed.

PMID- 7719144
TI  - Congenital symmetrical weakness of the upper limbs resembling brachial plexus
      palsy: a possible sequel of drug toxicity in first trimester of pregnancy?
AB  - We report a 14-month-old girl with a symmetrical paralysis from birth, limited to
      the upper limbs and resembling a severe, complete bilateral brachial plexus
      palsy. The presence of dimples over the wrists, shoulders and scapulae and
      abnormal palmar dermatoglyphics suggested an early prenatal onset. Previous
      reports and the course of the disease in our case suggest this sporadic condition
      is not progressive. Although no definitive causative factor has been identified
      in previously reported cases, the affection in our case is possibly related to
      Debendox (Bendectin) and nitrofurantoin taken in early pregnancy for nausea and
      renal tract infection, respectively.

PMID- 7719145
TI  - Absence of mutations in the Mn superoxide dismutase or catalase genes in familial
      amyotrophic lateral sclerosis.
AB  - Familial amyotrophic lateral sclerosis (FALS) is an autosomal dominant, adult
      onset, neurological disorder caused by the degeneration of motor neurons of the
      cortex, brainstem and spinal cord. Recently, the defective gene in some FALS
      families was identified as the Cu/Zn superoxide dismutase (SOD1) gene. However,
      SOD1 mutations are present in approximately 20% of patients with FALS. We have
      tested the genes of two more free radical detoxifying enzymes, Mn superoxide
      dismutase (SOD2) and catalase by single strand conformation analysis (SSCA) for
      mutations in the remaining FALS cases. No mutations were found in the catalase
      enzyme in 73 unrelated FALS cases; mutations were not detected in the 66% of the
      SOD2 gene analyzed. FALS does not appear to be caused by mutations in the SOD2
      nor the catalase genes.

PMID- 7719146
TI  - Diagnostic criteria for the limb-girdle muscular dystrophies: report of the ENMC
      Consortium on Limb-Girdle Dystrophies.

PMID- 7719147
TI  - 11th meeting of the Peripheral Nerve Study Group (PNSG). "Klostergut Jakobsberg",
      Boppard, Germany 29 July-1 August 1993.

PMID- 7719148
TI  - Role of endothelial cells in transplantation.
AB  - Endothelial cell activation with accompanying vascular inflammatory changes is
      considered central to the experimental manifestations of both hyperacute and
      delayed xenograft rejection responses. Natural xenoreactive antibodies directed
      at alpha-galactosyl residues of xenogeneic glycoproteins and glycolipids, with
      associated complement activation via the classical pathway, are considered major
      immediate mediators of graft endothelial cell injury in the clinically relevant
      discordant swine to primate combinations. In delayed xenograft rejection
      processes, where recipients are treated prophylactically to ameliorate these
      initial events, activation of infiltrating mononuclear phagocytes and natural
      killer cells are associated with ongoing endothelial cell activation processes,
      procoagulant generation and vascular thrombosis. Allograft hyperacute rejection
      is observed when vascularised organs are transplanted to sensitized individuals
      with high levels of cytotoxic antibodies. Less dramatic forms of humoral
      allograft rejection (termed accelerated or vascular rejection) and the more
      common cell-mediated endothelialitis are associated with significant graft
      damage. Endothelial cell activation is also linked with graft preservation
      injury, forms of chronic rejection and delayed graft loss. Experimental work is
      currently being directed at the control of hyperacute rejection, the close
      understanding of endothelial cell thromboregulation in both transplanted xeno-
      and allografts and the development of novel therapeutic agents including gene
      therapy and the possible use of organs from transgenic animals.

PMID- 7719149
TI  - Knockout mice: how to make them and why. The immunological approach.
AB  - Transgenic technology has developed at breakneck speed in the past years. The
      establishment of embryonic stem cells and the finding that they can serve as
      bridge between genetic manipulations in vitro and biological analysis in vivo
      enabled the systematic creation of mouse strains with defined genetic
      alterations. This review lists the strategies which can be used to alter the
      genetic makeup of mice and summarizes some of the results which have been
      obtained in genetically altered mice of immunological interest.

PMID- 7719150
TI  - Adhesion of lymphocytes to endothelial cells in experimental allergic
      encephalomyelitis before and after treatment with endotoxin lipopolysaccharide.
AB  - We investigated the in vitro adhesion of 51Cr-labeled lymphocytes to cultured
      brain endothelial cells and the in vivo expression of intercellular adhesion
      molecule-1 (ICAM-1) on cerebral endothelial cells in a rat model of experimental
      allergic encephalomyelitis (EAE) before and after treatment with
      lipopolysaccharide (LPS). Adhesion of lymphocytes to cerebral endothelial cells
      was significantly increased in EAE compared with controls (p < 0.01), and was
      significantly correlated with the percentage of major histocompatibility complex
      class II antigen-positive cells in lymph node cells (p < 0.001). LPS enhanced
      ICAM-1 expression on endothelial cells and lymphocyte adhesion to those cells,
      and caused a significant increase in the in vivo expression of ICAM-1 compared
      with controls (p < 0.001). Lymphocyte adhesion to endothelial cells was
      significantly blocked by monoclonal antibodies against ICAM-1, lymphocyte
      function-associated antigen-1, or very late activation antigen-4. Our findings
      suggest that lymphocyte adhesion to brain endothelial cells may contribute to
      lymphocyte migration across the blood-brain barrier in EAE and that LPS may cause
      progression of EAE lesions.

PMID- 7719151
TI  - Adhesion molecules in the nickel allergic reaction.
AB  - Nickel is the major cause of allergic contact dermatitis, and to increase our
      understanding of this immune reaction we studied changes in the expression of
      adhesion molecules on mononuclear cells during nickel stimulation in vivo and in
      vitro. Nickel-induced lymphocyte cultures were used in vitro, the cells being
      examined with monoclonal antibodies (Mabs) and by flow cytometry. Mononuclear
      cells from skin biopsies of in vivo cutaneous nickel reactions were studied with
      Mabs and immunohistochemistry. The expression of adhesion molecules in vitro was
      differential: the number of cells carrying CD11c, CD29, CDw49b, CDw49d, CDw49e,
      CDw49f, CD54, CD56 and ELAM-1 being significantly overrepresented among the
      nickel-induced lymphoblasts whereas the number of blasts carrying CD44 was
      underrepresented and those of CD11a, CD18, CD58 and LAM-1 remained unchanged.
      CD4+ cells gained adhesion molecules during nickel-induced blast transformation
      whereas CD8+ cells lost most of their adhesion molecules. The in vivo results
      were in agreement with the in vitro ones except that CDw49b, CDw49f, CD56 and
      ELAM-1 could not be detected in a 96-hour nickel reaction in vivo. In conclusion,
      the nickel allergic reaction favors the expression of certain adhesion molecules,
      and this expression is induced on CD4+ cells while CD8+ cells tend to lose such
      molecules. The changes were more sensitively detected with the in vitro method.

PMID- 7719152
TI  - Interleukin-8 induces HLA-DR expression on cultured human keratinocytes via
      specific receptors.
AB  - Recent studies suggest that interleukin (IL)-8 exerts a direct influence on
      several functions such as the chemotaxis or proliferation of human keratinocytes
      (HK). Since the effects of IL-8 in skin are mediated through specific receptors,
      we have studied the characteristics of the keratinocyte IL-8 receptor. We could
      identify specific binding sites for IL-8 in cultured HKs by flow cytometry.
      Pretreatment of the cells with tumor necrosis factor (TNF)-alpha or IL-1 alpha
      resulted in a significant increase in IL-8 binding. IL-8 selectively induced
      expression of HLA-DR antigen, but had no effect on the expression of other cell
      surface antigens (CD11a, CD18, CD36 and CD54).

PMID- 7719153
TI  - Effect of Pseudomonas aeruginosa on interleukin-8 release from human phagocytes.
AB  - Pseudomonas aeruginosa infections are commonly observed in sepsis, burns, as well
      as cystic fibrosis (CF). Among the professional phagocytes neutrophils and
      monocytes are recruited by various chemotactic factors from the cellular
      environment. Although they provide the first line of host defense excessive
      neutrophil accumulation seems to be a major cause of pathogenesis during P.
      aeruginosa infection. Interleukin-8 (IL-8) represents one important
      chemoattractant for professional phagocytes. To evaluate IL-8 releasability by
      phagocytes in the context of P. aeruginosa infection and especially of CF, we
      stimulated human polymorphonuclear neutrophilic granulocytes (PMN) and peripheral
      blood mononuclear cells (PBMC) as a source for monocytes with clinical P.
      aeruginosa isolates, with mucoid P. aeruginosa strain (CF3M) and its nonmucoid
      revertant (CF3), and with purified P. aeruginosa mucoid exopolysaccharide
      (alginate). A significant increase in IL-8 release as compared to unstimulated
      cells was observed after an incubation time of 90 min for PMN and after 60 min
      for PBMC which increased (PMN: up to 60-fold; PBMC: up to 40-fold) over time (up
      to 4 h). In contrast of PBMC, when PMN were studied, intracellular IL-8 exceeded
      the IL-8 release in unstimulated as well as in stimulated cells by up to 10-fold.
      All clinical P. aeruginosa isolates, independent of the clinical source, induced
      IL-8 release from human PBMC and PMN in a dose- and time-dependent
      manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719154
TI  - Anti-CD4 activity in circulating immune complexes in HIV-infected patients.
AB  - Levels of circulating immune complexes (CIC) measured by precipitation with 1.04
      M ammonium sulfate ranged from 22 to 2,040 micrograms/ml in a group of 141 HIV
      infected patients. CIC were elevated (> 200 micrograms/ml) in 72.2% of infected
      individuals. When analyzed for their HIV antigen composition, those CIC
      containing HIV antigens were found more frequently in patients clinically
      affected (68.6%) than in asymptomatic individuals (31.4%; p < 0.001). Anti-CD4
      activity of 89 isolated CIC was detected in 43.8% of these patients, but only in
      7.6% of the cases these CIC could bind to native CD4+ molecules. CIC with anti
      CD4 activity could inhibit PHA stimulation of normal peripheral blood
      lymphocytes. Anti-CD4 activity in CIC was independent of the clinical and
      immunological status of HIV-infected patients.

PMID- 7719155
TI  - Rat antibodies bearing idiotypes of mouse antibodies against bromelain-treated
      mouse RBC.
AB  - Part of mouse antibodies reactive with bromelain-treated mouse RBC (BrMRBC) use
      VH12 and VK4 genes, and VH12/VK4-type antibodies are detectable specifically with
      rabbit anti-idiotype (Id) antibodies (here referred to as RAIb). This study
      showed that normal rat sera contained RAIb+ IgM at concentrations of 1-6
      micrograms/ml. Rat spleens had many anti-BrMRBC B cells, most of which secreted
      RAIb+ IgM. Hybridomas of spleen cells from LPS-injected rats were screened with
      RAIb-binding and BrMRBC-hemolytic activity. We found 48 BrMRBC-hemolytic wells,
      which included all of 39 RAIb(+)-wells. From anti-BrMRBC wells, 7 RAIb+
      monoclonal antibodies (mAb) were isolated. All the RAIb+ mAb could react with
      phospholipid antigens. Rat RAIb+ antibodies, as well as mouse RAIb+ antibodies,
      can be regarded as antiphospholipid antibodies reactive with BrMRBC. The
      interspecies expression of RAIb-Id on mouse and rat anti-BrMRBC antibodies
      indicates that some (antigenic) selective forces may act strongly to conserve the
      Id (V genes).

PMID- 7719156
TI  - Effect of methotrexate on asthmatic reaction in sensitized guinea pigs.
AB  - To understand the mechanism of antiasthmatic property of the antimetabolite
      agent, methotrexate (MTX), we examined its effect on time-related changes in
      specific airway resistance, bronchial responsiveness, and accumulation of
      lymphocytes and eosinophils in lung tissue and the bronchial lumen, before and
      after antigen challenge in ovalbumin (OA)-sensitized guinea pigs. Intraperitoneal
      administration of MTX significantly inhibited the antigen-induced late asthmatic
      responses (LAR) in actively sensitized animals in dose-dependent manner.
      Examination of bronchoalveolar lavage fluid (BALF) revealed that 0.25, 0.5 and
      1.0 mg/kg body weight of MTX significantly inhibited the recruitment of
      eosinophils, lymphocytes (6 and 24 h after antigen challenge) and neutrophils
      (0.5, 6 and 24 h after antigen challenge) in the airways in a dose-dependent
      manner. Histological examination of lung tissue revealed that MTX significantly
      inhibited eosinophil infiltration into the airway (6 and 24 h after antigen
      challenge). Furthermore, MTX significantly inhibited the infiltrations of PKH-2
      labeled peripheral blood mononuclear cells (mostly lymphocytes) into the airways
      (24 h after antigen challenge). MTX also inhibited airway hyperresponsiveness to
      methacholine following OA challenge in a dose-dependent manner. We conclude that
      the antiasthmatic effect of methotrexate is mainly due to inhibition lymphocytes
      and eosinophil infiltration into the airway.

PMID- 7719157
TI  - Chronic sinusitis: characterization of cellular influx and inflammatory mediators
      in sinus lavage fluid.
AB  - Chronic sinusitis is a recurrent disorder commonly found in atopic individuals,
      yet few studies have explored the role of inflammatory mediators in sinusitis.
      Sinus lavage fluid from ten patients with chronic sinusitis obtained during
      endoscopic surgery was analyzed for total cell counts and then assayed for
      histamine, immunoreactive leukotriene C4/D4/E4 (LTC4/D4/E4), and prostaglandin D2
      (PGD2). All ten patients had been unresponsive to medical treatment, including
      oral corticosteroids in most cases. High concentrations of histamine, LTC4/D4/E4
      and PGD2 were found in sinus fluid and were comparable to levels seen in nasal
      secretions of allergic rhinitis patients following allergen challenge. In the
      sinus fluid, inflammatory cells were predominantly neutrophils with only low
      percentages of mast cells, basophils or eosinophils. On the basis of the
      histamine and PGD2 concentrations in sinus fluid, we conclude that mast
      cell/basophil activation does occur in chronic sinusitis and may contribute to
      the persistent inflammation present in sinusitis.

PMID- 7719158
TI  - Increased IgE antiovalbumin level in mice exposed to formaldehyde.
AB  - The effect of formaldehyde exposure on the sensitization of mice to ovalbumin was
      investigated. Significantly increased IgE antiovalbumin titers were found in mice
      sensitized intranasally to ovalbumin and exposed for 10 days to 2 mg/m3 of
      formaldehyde. In contrast, mice not exposed to formaldehyde or exposed once a
      week produced low levels of this antibody. The exposure of mice, sensitized
      intraperitoneally with ovalbumin, to formaldehyde did not increase sensitization.
      It was concluded that formaldehyde facilitates sensitization of mice to ovalbumin
      by changes that occur in the respiratory tract.

PMID- 7719159
TI  - Chronic granulomatous disease assessed by single-cell granulocyte oxidative burst
      activity.
AB  - Here we report on a case of chronic granulomatous disease (CGD) in a 3-year-old
      boy who suffered from severe repeated bacterial infections including multiple
      liver abscesses. The case is of interest because (1) the disease is very rare (it
      is the first case of CGD diagnosed at the Clinic for Pediatric Medicine,
      University of Innsbruck), (2) the diagnosis, based on clinical parameters and the
      nitrobluetetrazolium test was completed and validated by single-cell measurements
      of respiratory-burst activity of the patient's granulocytes in a fluorescence
      activated cell sorter (FACS), and (3) the applied FACS method, adapted in our
      laboratory, presents one of the most sensitive and reliable methods to evaluate
      this aspect of disturbed granulocyte function.

PMID- 7719160
TI  - Possible presence of RANTES in tears of patients with allergic conjunctivitis.

PMID- 7719161
TI  - [Proceeding of the annual meeting of the Austrian Association of Gynecology &
      Obstetrics. Bregenz, June 1994].

PMID- 7719162
TI  - [Use of pediatric laparoscopy for nonpalpable testis].
AB  - Children with nonpalpable testes create a clinical dilemma because it is
      difficult to determine the location or absence of the testis by clinical
      examination. Twenty-two children with unilateral nonpalpable tests underwent
      successful laparoscopic management under general anesthesia. In 11 (50%) of the
      patients, the vas deferens and the spermatic vessels exited the internal inguinal
      ring via the normal anatomy. Either hypoplastic testes or inguinal vanishing
      testes were found during inguinal exploration in 8 children with normal anatomy
      but smaller spermatic vessels exiting the internal inguinal ring. Four patients
      (18%) with blind end of vas and vessels terminating proximal to the internal
      inguinal ring were considered to be cases of intra-abdominal vanishing testis and
      no further surgery was necessary. Laparoscopy revealed 7 intra-abdominal testes
      (32%) which were managed by laparoscopic orchiectomy, simple orchiopexy, trans
      abdominal orchiopexy or laparoscopic staged orchiopexy depending on the patient's
      age and the gonadal intra-abdominal location.

PMID- 7719163
TI  - [Complications and management of percutaneous central venous access catheter].
AB  - The recently developed method of percutaneous subclavian implantation of an
      indwelling central venous catheter provides convenient access for patients
      requiring long-term intravenous therapy. To evaluate, clinical complications and
      its management, we reviewed 145 implanted central venous systems in 135 patients
      during a 7 month period. The implantation failed in two patients due to difficult
      subclavian punctures. The major complications were pinch-off sign observed in 5
      patients, inflammation in 6 patients (4.2%), and subclavian vein thrombosis in 7
      patients, and other miscellaneous complications in 7 patients. It was revealed
      the pressure between the clavicle and first rib attributed to "pinch-off sign",
      which could be avoided by a lateral subclavian vein approach. Meticulous
      disinfection before use of the system is advised since most infections was
      derived from the injection site. We also suggest the the catheter should be
      placed at the lower part of the superior vena cava because the development of
      thrombosis is highly poelated. Seven patients required removal of the system,
      however, all patients with complications had good Port A function adequate
      management or revision operation. Percutaneous subclavian implantation of
      indwelling central venous catheter is safe and reliable.

PMID- 7719164
TI  - [Clinical application of the ice water test in evaluation of neurogenic bladder
      dysfunction].
AB  - Ice water test (IWT) and cystometrography (CMG) were performed on 51 in patients
      with spinal cord injuries (SCI) to evaluate the sensitivity and specificity of
      the IWT in detecting detrusor reflex. A three-step grading system as established
      by Balmaseda et al was applied to determine the presence of detrusor activity on
      IWT. The test was considered 3+ when the catheter was expelled from the bladder
      within one minute following instillation of 90 mL of ice water; a 2+ test
      indicated voiding around the catheter after instillation of 90 mL of ice water;
      and a 1+ IWT was defined as voiding around the catheter or expelling the catheter
      after instilling another 210 mL of ice water into the bladder. The results showed
      that the sensitivity of IWT in detecting the presence of detrusor reflex in
      patients with neurogenic bladder dysfunction was 96% and the specificity was 79%.
      Among the four patients having false positive IWT, three of them were diagnosed
      with poor-compliance bladders. One patient with false negative IWT was found to
      have severe detrusor-sphincter dyssynergy. There was a significant difference in
      the strength of detrusor activity among the patients with 3+ IWT, with 2+ IWT,
      and with 1+ IWT. IWT is a useful technique to predict the existence of detrusor
      reflex in SCI patients. Its use as a supplement method to cystometrogram could be
      helpful in the bedside evaluation of patients with neurogenic bladder
      dysfunction.

PMID- 7719165
TI  - [Gastric cancer in Taiwan].
AB  - The study of gastric cancer is important in clinical medicine as well as in
      public health. Environmental factors play an important role in gastric
      carcinogenesis and thus primary prevention is feasible after improvement of these
      factors. The 5-year survival rate of resected early gastric cancer is over 90%
      and this provides an excellent paradigm for secondary prevention. Though its
      mortality rate has declined since 1970, gastric cancer remains common and carries
      a high mortality in Taiwan where about 2,000 patients die of gastric cancer
      annually. The age-adjusted mortality is 16.54 and 8.16/100,000 for male and
      female, ranking the third and fourth cancer death respectively. Epidemiologic
      data disclose a positive association between gastric cancer and some dietary
      factors in Taiwan. However, the role of Helicobacter pylori infection and
      hereditary susceptibility should be elucidated in the future. Endoscopy with
      biopsy is an excellent method of the diagnosis of gastric cancer. However, its
      invasiveness makes it impractical as a screening tool and thus the proportion of
      early gastric cancer to gastric cancer remains as low as 30% in most reports. The
      value of lymph node dissection remains controversial although surgery is one of
      the most effective methods of eradicating gastric cancer. Overall, the 5 year
      survival rate is 24.5% to 54%. Laser therapy is usually reserved for patients
      with high operative risk and specific types of gastric cancer. To improve the
      survival results, development of a simple and economic screening program based on
      the epidemiologic results and utilization of noninvasive examinations such as
      serologic markers to diagnose and treat gastric cancer at its earliest stage
      deserves further study.

PMID- 7719166
TI  - [Moyamoya disease in Taiwan].
AB  - From January 1978 to December 1993, 73 patients with moyamoya disease were
      collected from seven neurological centers in Taiwan. The annual incidence of this
      disease in Taiwan is 0.024 per 100,000 population. There were 33 males and 40
      females. The ages ranged from 2 to 62 years with a peak incidence in the 31 to 40
      year age group (18 cases). Cerebral infarction occurred in 16 out of 19 juvenile
      patients (84.2%); by contrast, only 19 out of 54 adult patients (35.2%) presented
      with infarction. Hemorrhagic strokes were more frequent in adult patients.
      Computed tomographic scans following stroke showed cerebral infarction in 35
      cases, ventricular hemorrhage in 21 cases, intracerebral hemorrhage in 11 cases
      and pure subarachnoidal hemorrhage in 6 cases. The most frequent initial symptom
      was motor disturbance (58.9%), followed by headaches (49.3%), and impaired
      consciousness (34.2%). Compared with reports from Japan, this survey showed a
      lower incidence of moyamoya disease in Taiwan.

PMID- 7719167
TI  - Epilepsy and driving.

PMID- 7719168
TI  - Monitoring and supplemental oxygen during endoscopy.

PMID- 7719169
TI  - Professional negligence: a duty of candid disclosure?

PMID- 7719170
TI  - Hospital doctor's role in the Health of the Nation.

PMID- 7719171
TI  - Ethnic monitoring and equity.

PMID- 7719172
TI  - Sweden considers criminalising prostitution.

PMID- 7719173
TI  - Italy's patients with AIDS revolt.

PMID- 7719174
TI  - Commission seeks new law on damages.

PMID- 7719175
TI  - Reprimand for Dutch doctor who assisted suicide.

PMID- 7719176
TI  - Australian doctors go public over euthanasia.

PMID- 7719177
TI  - Doctors must honour living wills,.

PMID- 7719178
TI  - Efficacy of tricyclic drugs in treating child and adolescent depression: a meta
      analysis.
AB  - OBJECTIVE: To examine whether tricyclic antidepressants are superior to placebo
      in the treatment of child and adolescent depression. DESIGN: Meta-analysis of 12
      randomised controlled trials comparing the efficacy of tricyclic antidepressants
      with placebo in depressed subjects aged 6-18 years. MAIN OUTCOME MEASURES: Most
      studies employed several depression rating scales. For each study the "best
      available" measure was chosen by using objective criteria, and individual and
      pooled effect sizes were calculated as the number of standard deviations by which
      the change scores for the treatment groups exceeded those for the control groups.
      Where authors had reported numbers "responding" to treatment we calculated
      individual and pooled ratios for the odds of improvement in treated compared with
      control subjects. RESULTS: From the six studies presenting data which enabled an
      estimation of effect size the pooled effect size was 0.35 standard deviations
      (95% confidence interval of -0.16 to 0.86) indicating no significant benefit of
      treatment. From the five studies presenting data on the number of "responders" in
      each group, the ratio of the odds of a response in the treated compared with the
      control subjects was calculated and the pooled odds ratio was 1.08 (95%
      confidence interval of 0.53 to 2.17); again indicating no significant benefit of
      treatment. The pooled sample had more than an 80% chance of detecting a treatment
      effect of 0.5 standard deviations or greater. There was an inverse relation
      between study quality and estimated treatment effect. CONCLUSIONS: Tricyclic
      antidepressants appear to be no more effective than placebo in the treatment of
      depression in children and adolescents.

PMID- 7719179
TI  - Do changes in cardiovascular risk factors explain changes in mortality from
      stroke in Finland?
AB  - OBJECTIVES: To estimate the extent to which the changes in the main
      cardiovascular risk factors (blood pressure, smoking, and serum cholesterol
      concentration) can explain the observed changes in mortality from stroke in
      Finland during the past 20 years. DESIGN: Predicted changes in mortality from
      cerebrovascular disease mortality were calculated by a proportional hazards model
      from data obtained in cross sectional population surveys in 1972, 1977, 1982,
      1987, and 1992. Predicted changes were compared with the observed changes in
      mortality statistics. SETTING: North Karelia and Kuopio provinces, Finland.
      SUBJECTS: 16,741 men and 16,389 women aged 30-59 randomly selected from the
      national population register, of whom 14,054 men and 14,546 women participated.
      MAIN OUTCOME MEASURES: Levels of risk factors and predicted and observed changes
      in mortality from cerebrovascular disease. RESULTS: The observed changes in
      diastolic blood pressure, total serum cholesterol concentration, and smoking in
      the population from 1972 to 1992 predicted a 44% fall in mortality from stroke in
      men and changes in diastolic blood pressure and smoking predicted a 34% fall in
      women. The observed fall in mortality from stroke was 66% in men and 60% in
      women. CONCLUSIONS: Two thirds of the fall in mortality from stroke in men and
      half in women can be explained by changes in the three main cardiovascular risk
      factors.

PMID- 7719180
TI  - Differences in mortality after fracture of hip: the east Anglian audit.
AB  - OBJECTIVE: To investigate differences between hospitals in clinical management of
      patients admitted with fractured hip and to relate these to mortality at 90 days.
      DESIGN: A prospective audit of process and outcome of care based on interviews
      with patients, abstraction from records with standard proforma, and follow up at
      three months. Data were analysed with chi 2 test and forward stepwise regression
      modelling of mortality. SETTING: All eight hospitals in East Anglia with trauma
      orthopaedic departments. PATIENTS: 580 consecutive patients admitted for fracture
      of neck of femur. MAIN OUTCOME MEASURE: Mortality at 90 days. RESULTS: Patients
      admitted to each hospital were similar with respect to age, sex, pre-existing
      illnesses, and activities of daily living before fracture. In all, 560 (97%) were
      treated surgically, by a range of grades of surgeon. Two hundred and sixty one
      patients (45%; range between hospitals 10-91%) received pharmaceutical
      thromboembolic prophylaxis, 502 (93%; 81-99%) perioperative antibiotic
      prophylaxis. The incidence of fatal pulmonary emboli differed between patients
      who received and those who did not receive prophylaxis against deep vein
      thrombosis (P = 0.001). Mortality at 90 days was 18%, differing significantly
      between hospitals (5-24%). One hospital had significantly better survival than
      the others (odds ratio 0.14; 95% confidence interval 0.04-0.48; P = 0.0016).
      CONCLUSIONS: No single factor or aspect of practice accounted for this protective
      effect. Lower mortality may be associated with the cumulative effects of several
      aspects of the organisation of treatment and the management of fracture of the
      hip, including thromboembolic pharmaceutical prophylaxis, antibiotic prophylaxis,
      and early mobilisation.

PMID- 7719181
TI  - Safety and efficacy of combined meningococcal and typhoid vaccine.

PMID- 7719182
TI  - Abnormality rates on barium meal examination in different racial groups.

PMID- 7719183
TI  - Management of dyspepsia among Asians by general practitioners in east London.

PMID- 7719184
TI  - Self screening for risk of melanoma: validity of self mole counting by patients
      in a single general practice.
AB  - OBJECTIVE: To validate self screening by patients of high mole counts, assess the
      within family association of sun protection behaviour and mole counts, and
      estimate prevalence of risk factors for melanoma. SETTING AND SUBJECTS:
      Systematic sample of families from a single affluent general practice population
      in Wessex. DESIGN: Subjects completed a questionnaire about risk factors for
      melanoma and counted their moles. Subsequently a mole count was done by a general
      practitioner trained at dermatology clinics. MAIN OUTCOME MEASURES: Validation of
      self counts by observer's count. Within family association of sun protection
      behaviour and mole counts; self reported risk factors. RESULTS: 199/237 subjects
      (84%) returned the questionnaire; 212/237 (89%) were examined. High counts by
      patients on the front of the trunk (> 7 moles of > or = 2 mm) were reasonably
      sensitive (79%), predictive (75%), and specific (97%) of the observer's mole
      counts (kappa = 0.74), unlike arm or total body counts. Sun protection behaviour
      correlated between individuals and other family members (Spearman's coefficient r
      = 0.50, P < 0.01). In the past three months 15/114 adults (13.2%, 95% confidence
      interval 7.0% to 19.4%) reported any change in a mole and 6/114 (5.3%, 2.0% to
      11.1%) "major" changes; 6/109 adults (5.5%, 2.1% to 11.6%) had both high mole
      counts and freckling. CONCLUSIONS: Asking patients to count trunk moles could be
      a feasible way of identifying patients at high risk of melanoma. Concentrating on
      reported major changes in moles should avoid considerable workload in general
      practice. The generalisability of these findings and the adverse effects, net
      benefit in earlier diagnosis and prevention, and workload implications of such
      self screening need further research.

PMID- 7719185
TI  - Screening for melanoma risk is misguided.

PMID- 7719186
TI  - Orthopaedic and trauma surgery.

PMID- 7719187
TI  - Reporting research in medical journals and newspapers.
AB  - Newspapers are important sources of information about medical advances for many
      lay people and can influence those working in the health service. Medical
      journalists on newspapers routinely use general medical journals to obtain
      information on research. The Lancet and BMJ are both examined carefully by
      broadsheet journalists in Britain each week. These papers published an average of
      1.25 stories from these journals every Friday. The stories focused on serious
      diseases, topical health problems, and new treatments rather than social
      problems. The newspaper stories were based on the full research article and not
      the journals' press releases, although the press releases were valued as early
      information. Journalists relied heavily on the peer review processes of the
      journals in ensuring accuracy.

PMID- 7719188
TI  - What constitutes good prescribing?
AB  - Drugs are the mainstay of medical treatment, yet there are few reports on what
      constitutes "good prescribing." What is more the existing guidance tends to imply
      that right answers exist, rather than recognising the complex trade offs that
      have to be made between conflicting aims. This paper proposes four aims that a
      prescriber should try to achieve, both on first prescribing a drug and on
      subsequently monitoring it. They are: to maximise effectiveness, minimise risks,
      minimise costs, and respect the patient's choices. This model of good prescribing
      brings together the traditional balancing of risks and benefits with the need to
      reduce costs and the right of the patient to make choices in treatment. The four
      aims are shown as a diagram plotting their commonest conflicts, which may be used
      as an aid to discussion and decision making.

PMID- 7719189
TI  - Alternative models of organisation are needed.
AB  - Anyone considering a fundamental rethink of the role of consultants risks
      exposing tensions in the medical profession that have characterised the
      development of medical practice since the 18th century. That tense story was one
      of beds and money, power and domination. Rethinking the role of consultants must
      now take into account the relationship between consultants and their specialist
      colleagues and general practitioners; examine the distribution of work between
      consultants and junior doctors; and relate the contribution of the consultant as
      specialist to that of other health professionals. After half a century of a
      national health service characterised by equity of access to care, we urgently
      need to debate the roles of those who work in it and in doing so to focus
      primarily on the needs of patients.

PMID- 7719190
TI  - ABC of rheumatology. Low back pain.

PMID- 7719191
TI  - A fundamental problem of consent. Dentist is aggrieved at outcome.

PMID- 7719192
TI  - A fundamental problem of consent. Nothing is inherently remiss in present methods
      of obtaining consent.

PMID- 7719193
TI  - A fundamental problem of consent. Patients' should be able to say no.

PMID- 7719195
TI  - A fundamental problem of consent. GMC may not be entitled to conclude that
      assault occurred.

PMID- 7719194
TI  - A fundamental problem of consent. Consent forms are unhelpful.

PMID- 7719196
TI  - A fundamental problem of consent. GMC prefers "prudent patient" test.

PMID- 7719197
TI  - A fundamental problem of consent. Fact sheets may be useful.

PMID- 7719198
TI  - A fundamental problem of consent. Patients' views have been surveyed.

PMID- 7719199
TI  - A fundamental problem of consent. Rectogenital region is associated with strong
      cultural and sexual aesthetic beliefs.

PMID- 7719200
TI  - American Medical Association condemns acts of terrorism against health care
      workers.

PMID- 7719201
TI  - Electoral reform of GMSC.

PMID- 7719202
TI  - Junior doctors' hours. Position of the "English clause" is uncertain.

PMID- 7719203
TI  - National survey of hospital patients. Has a management dominated agenda.

PMID- 7719204
TI  - Non-immunisation of children. Statistics on vaccination coverage may be a poor
      measure of practice performance.

PMID- 7719205
TI  - Non-immunisation of children. The Society of Homoeopaths has no official policy
      on vaccination.

PMID- 7719206
TI  - Drug resistant tuberculosis.

PMID- 7719207
TI  - Measles and rubella immunisation.

PMID- 7719208
TI  - Non-immunisation of children. Book dispelling immunisation myths is available.

PMID- 7719209
TI  - Chickenpox in the tropics.

PMID- 7719210
TI  - Differences in progression of HIV infection between men and women.

PMID- 7719211
TI  - Heart muscle disease related to HIV infection.

PMID- 7719212
TI  - Antibiotics carried in general practitioners' emergency bags.

PMID- 7719213
TI  - Supplementation with folic acid.

PMID- 7719214
TI  - Units of measurement of central venous pressure.

PMID- 7719215
TI  - Clinical Negligence Scheme for Trusts. Department of Health's view.

PMID- 7719216
TI  - Hepatitis C in asymptomatic blood donors.

PMID- 7719217
TI  - Ocular injuries due to alkaline substances.

PMID- 7719218
TI  - Chemoprevention of second primary tumours in head and neck cancer in Europe:
      EUROSCAN.

PMID- 7719219
TI  - A population-based study of prognostic factors in oral and oropharyngeal cancer.
AB  - Cases of oral cavity and oropharynx cancer diagnosed among the residents of
      Torino, Italy, between 1982 and 1984 (n = 143) were followed up to June 1990.
      During this period, 97 subjects (67.8%) died, 69 from oral or oropharyngeal
      cancer. 10 more cases died from causes possibly related to oral cancer. The
      overall relative 5-year survival rate was 37.2%. Men experienced a worse survival
      than women. No difference was shown according to age, education or occupation.
      Patients with smooth lesions had a poorer prognosis than those with fissured or
      granular lesions; no association between survival and colour, elevation,
      induration or bleeding from the lesion was found. Extension of the tumour and
      nodal involvement were strong and independent predictors of survival, but no
      difference was found between T1 and T2 lesions. Patients who reported a 2-3-month
      interval between onset of symptoms and diagnosis experienced a better survival
      than those with shorter or longer interval. Oropharynx cases had a better
      prognosis than cancers of the oral cavity.

PMID- 7719220
TI  - Radical surgical treatment in craniofacial osteosarcoma gives excellent survival.
      A retrospective cohort study of 14 patients.
AB  - 14 patients with an osteosarcoma of the craniofacial bones were evaluated
      retrospectively. 10 patients were males and 4 were females, ages varied from 10
      to 74 years with a mean of 37 years. Ten tumours were located in the maxilla and
      four in the mandible. All patients underwent surgical resection of the tumour.
      One patient was irradiated postoperatively with 67.5 Gy and another patient
      received adjuvant chemotherapy with melphelan. Follow-up ranged from 6 months to
      10 years with a mean of 4 years 2 months. Of 14 patients, 5 have died of local
      disease of whom 1 also had distant metastasis. Disease-free survival was 82.5%
      after 2 years and 68.8% after 5 years. Overall survival was 79.1% after 5 years.
      Univariate statistical analysis was carried out, revealing age < 35 years (P =
      0.033) and radical surgery (P = 0.007) as statistically significant factors in
      disease-free survival. It is concluded that radical surgery in young patients
      with a craniofacial osteosarcoma gives long-term disease-free survival.

PMID- 7719221
TI  - Second cancers following oral and pharyngeal cancer: patients' characteristics
      and survival patterns.
AB  - A survey was made of second primary cancers among patients who were enrolled in a
      large case-control investigation of oral and pharyngeal cancer, hereafter called
      oral cancer, during 1984-1985 in four areas of the United States. Among the
      original 1090 patients with oral cancer (nearly all squamous cell carcinomas),
      107 developed a second cancer (one-half of them squamous cell) by the end of
      follow-up in June 1989 (average follow-up 2.6 years), with 69% occurring in the
      oral cavity, pharynx, oesophagus, larynx or lung. Rates of second tumours varied
      by age and socioeconomic status, but not sex or race, and were higher among those
      whose initial cancer was localised, even after adjusting for their longer
      survival. Long-term survival was lower among those with second cancers.
      Conditional on surviving for 2 years, the survival at 5 years was under 50% and
      nearly 70%, respectively, for those with versus those without a second cancer in
      the first 2 years. These findings confirm the exceptionally high rate of second
      cancers (especially of the aerodigestive tract) following oral cancer, describe
      the clinical and pathological features of patients with multiple cancers and
      indicate the importance of preventive measures.

PMID- 7719222
TI  - A return to "normal eating" after curative treatment for oral cancer. What are
      the long-term prospects?
AB  - The ability to eat determines not only a patient's nutritional status, but also
      influences quality of life. A retrospective investigation of the incidence of
      side-effects affecting eating and their effect upon quality of life more than 1
      year after treatment, was undertaken to evaluate long-term patient
      rehabilitation. 25 patients with oropharyngeal carcinoma were interviewed.
      Nutritional intake and effect on diet were assessed by analysis of patient diet
      diaries. Nutritional status was measured from weights recorded at time of
      treatment and anthropometric measurements at time of study. All patients
      completed a quality-of-life questionnaire and the importance of side-effects was
      measured by a ranking exercise. Seventy-two per cent of patients required
      modifications of dietary consistency. Energy and protein intakes decreased with
      increasing degrees of dietary modification. Side-effects affecting eating
      persisted in 23 out of 25 patients, with 80% still having a dry mouth at a mean
      of 3.5 years post-treatment. Forty per cent had not regained weight lost during
      treatment. The top ranked side-effects perceived to be of greatest importance to
      quality of life all related to the ability to eat. A return to "normal eating" is
      not possible in all patients.

PMID- 7719223
TI  - Scanning electron microscopy of different types of oral leukoplakia: comparison
      with normal and malignant oral mucosa.
AB  - The present study analysed surface architecture of normal, premalignant and
      malignant oral mucosa using scanning electron microscopy to evaluate its role in
      early diagnosis of potentially malignant oral lesions. The surface ultrastructure
      of the buccal mucosa in tobacco chewers showed variations from that of non
      chewers. Homogenous leukoplakia demonstrated well-defined intercellular junctions
      and the microrugal surface pattern as seen in normal mucosa. In verrucous
      leukoplakia, the surface layer consisted of characteristically-shrunken
      desquamated hyperkeratotic cells. Erosive leukoplakia had a discontinuous
      superficial layer along with complete loss of intercellular ridges. Speckled
      leukoplakia also showed marked abnormalities such as thickened irregular
      protrusions and evidence of a villus-like pattern. These villus-like structures
      were comparatively prominent in leukoplakia showing dysplasia. Oral carcinoma
      showed marked altered surface ultrastructure and had a pattern similar to
      dysplastic lesions. The irregular swollen elongated protrusions with villous-like
      structures that were observed in carcinoma and dysplastic lesions can, therefore,
      be considered as surface markers for potentially malignant leukoplakia.

PMID- 7719224
TI  - Determinants of compliance with an early detection programme for cancer of the
      head and neck in north-eastern Italy.
AB  - An early detection programme for cancer of the head and neck (H&N) has been
      conducted from January 1991 to January 1993 in Pordenone province, north-eastern
      Italy, an area with very high mortality rates for cancers in those sites. 627
      high-risk individuals (491 males, median age 57 years and 136 females, median age
      47 years) (i.e. smokers and/or drinkers of more than a half litre of wine or
      equivalent per day) were referred to a research nurse by 21 general
      practitioners. An educational message on the health hazards of tobacco and
      alcohol abuse was delivered together with an invitation to undergo a free ear,
      nose and throat (ENT) examination at a nearby hospital. 212 individuals (34%)
      underwent the ENT visit. The influence of various individuals' characteristics on
      the lack of compliance was assessed. Female sex and absence of ENT symptoms were
      associated with a more than two-fold higher lack of compliance. Current smokers
      were more than three-fold less likely to accept the invitation to undergo the
      examination. Conversely, alcohol intake and, within smokers, the amount smoked
      seemed unimportant. This study shows that the correct identification of high-risk
      individuals is expensive and the compliance with a H&N cancer early detection
      programme relatively low, especially among smokers.

PMID- 7719225
TI  - p53 and PCNA expression in carcinogenesis of the oropharyngeal mucosa.
AB  - Hyperplastic lesions of the oral mucosa such as leukoplakia and oral lichen
      planus can eventually develop into squamous cell carcinomas (SCC) and provide an
      excellent model for multistage carcinogenesis. The development of carcinomas is
      assumed to be the result of interaction of genetic factors, locally applied
      carcinogens and immunological unresponsiveness. The purpose of this study was,
      therefore, to determine the role of alterations of the tumour suppressor gene
      p53, and the proliferation status of the lesions determined by PCNA expression.
      We investigated p53 and PCNA expression in 265 tissue sections of normal mucosa,
      premalignant, malignant and metastatic lesions of the oral mucosa by
      immunohistology. Quantitative analysis showed a gradual increase in PCNA
      expression from normal mucosa to moderately differentiated SCC. p53 expression
      was detectable in benign premalignant lesions. The increase in the number of p53
      positive biopsies was correlated with the dysplasia and loss of differentiation
      in the premalignant and malignant lesions.

PMID- 7719227
TI  - Bispecific monoclonal antibody therapy of B-cell malignancy.
AB  - Bispecific monoclonal antibodies (bsAbs) that recognize CD3 with one arm and a
      tumor associated antigen with the other arm can retarget T-cells toward tumor
      cells in an MHC independent manner, thereby combining the specificity of
      monoclonal antibodies with the power of the cellular immune system. B-cell
      malignancies are particularly attractive as targets for anti-CD3-based bsAb
      therapy because of their sensitivity to other forms of antibody therapy, and the
      extent to which B-cells and T-cells communicate at the molecular level. BsAbs
      that recognize CD3 and a number of antigens on malignant B-cells have been shown
      in vitro to be capable of retargeting T-cells. In animal models of B-cell
      malignancy, bsAb can eliminate tumor loads that are resistant to unmodified
      monoclonal antibody therapy. Ongoing early clinical trials in advanced B-cell
      lymphoma indicate CD3-based bsAbs have significant biologic effects, and suggest
      they have anti-tumor activity as well. A number of significant questions relating
      to bsAb therapy of B-cell malignancies remain. It is unclear what role both
      endogenously produced and exogenously administered cytokines are likely to play.
      Further exploration of whether bsAb can induce T-cells to target to tumor will
      also be required before the true promise of this novel form of immunotherapy can
      be determined.

PMID- 7719226
TI  - Growth-factor stimulation reveals two mechanisms of retinoblastoma gene
      inactivation in human myelogenous leukemia cells.
AB  - Mutation or deletion of the retinoblastoma tumor suppressor gene (Rb) or abnormal
      Rb protein expression is found in many types of human solid tumors. Low or absent
      levels of Rb protein are usually found in the leukemic cells of patients with
      acute myelogenous leukemia (AML) who have an extremely poor prognosis. The
      absence of Rb protein in these AML cells could result from defects in the Rb gene
      or from abnormal cell cycle regulation that affects Rb expression. To test these
      possibilities and to examine whether a low level of Rb protein in AML cells could
      be up-regulated, we studied the effect that growth factors interleukin 3 (IL3)
      and granulocyte-macrophage colony stimulating factor (GM-CSF) had on the levels
      of Rb protein and Rb phosphorylation in AML cells from patients with low Rb or no
      Rb protein expression. We observed three responses to growth factor-stimulation
      in leukemic cells taken from patients with AML: (1) some AML cell samples entered
      a proliferative phase, and Rb protein levels increased with the appearance of
      normally phosphorylated forms of Rb protein and positive nuclear staining for Rb
      protein; (2) some AML cell samples became more proliferative, but the levels of
      Rb protein remained low or absent; and (3) some AML cell samples showed no
      response. These results indicate that at least two different mechanisms may be
      responsible for the lack of Rb protein in the leukemic cells of some patients
      with AML.

PMID- 7719228
TI  - Dysregulation of HOX11 by chromosome translocations in T-cell acute lymphoblastic
      leukemia: a paradigm for homeobox gene involvement in human cancer.
AB  - The translocation t(10;14)(q24;q11) is observed in the course of routine cancer
      cytogenetic studies in 5-10% of patients with T-cell acute lymphoblastic leukemia
      (ALL). Recent molecular dissections of t(10;14) translocations support the
      hypothesis that these relatively gross chromosomal mutations represent key
      genetic steps in neoplastic transformation. The genes consistently involved are
      the T-cell receptor (TCR) delta-chain gene in 14q11 and a human homeobox
      containing gene in 10q24, HOX11, initially identified through cloning of t(10;14)
      translocations. Like other homeoproteins, HOX11 binds DNA with sequence
      specificity and is likely to be a transcription factor, controlling the
      expression of developmentally important genes. The t(10;14) translocations arise
      as a result of aberrant physiological recombinational events that occur at early
      stages of T-cell development, probably during failed attempts at TCR gene
      rearrangement. The net result of the aberrant genetic recombinations is
      inappropriate expression of HOX11 in individual T-cells that acquire the
      mutation. Tlx-1, the murine homolog of HOX11, is expressed embryologically in the
      developing spleen and in structures derived from cranial neural crest cells and
      migratory paraxial mesoderm. Mice homozygously deleted for Tlx-1 are asplenic.
      Thus, HOX11 may be one of the first examples in mammals of a "master gene" acting
      as a regulatory switch controlling a downstream program of organ-specific cell
      growth and proliferation. Preliminary tumorigenicity assays suggest that HOX11
      expression in hematopoietic cells most likely plays an immortalization role in
      neoplastic transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719229
TI  - Epstein-Barr virus-associated non-Hodgkin's lymphoma in HIV-infected patients.
AB  - Epstein-Barr virus (EBV) has been implicated in the pathogenesis of many
      lymphoproliferations arising in diverse settings, including HIV-infection. The
      precise roles of EBV may differ between these settings. For example, both the
      frequencies of EBV-association and the specific c-MYC translocations differ
      between sporadic and African Burkitt's lymphoma. Similarly, the frequencies of
      EBV-association in HIV-infected patients differs between anatomical sites, types
      of NHL, and geographic locations. HIV-related NHL have genetic alterations
      similar to NHL arising in the general population, and have less in common with
      the lymphoproliferations which arise in the setting of transplantation. However,
      the patterns of latent EBV transcription in systemic HIV-related NHL is unique
      among NHL, suggesting that EBV may contribute differently to their pathogenesis.

PMID- 7719230
TI  - Biological features of leukaemic cells associated with autonomous growth and
      reduced survival in acute myeloblastic leukaemia.
AB  - The blast cells from up to 70% of patients with acute myeloblastic leukaemia
      exhibit a variable degree of autonomous growth in vitro, which is related to the
      production of autocrine growth factors. It has recently been established that
      patients with autonomous blast cell growth have both a lower remission rate and a
      higher relapse rate, compared to otherwise comparable patients whose blasts
      exhibit non-autonomous in vitro growth. In a group of 50 patients the actuarial
      disease-free survival for the autonomous growth group was 11% at 5 years compared
      to greater than 50% for the non-autonomous growth group. This data suggests that
      AML blasts with autocrine growth characteristics may be resistant to cytotoxic
      drug therapy. Here we present further data demonstrating that AML blasts with
      autonomous growth are relatively resistant to the induction of programmed cell
      death (apoptosis) and that this is related to the autocrine production of GM-CSF.
      Also AML blasts with autonomous growths have aberrant expression of genes
      associated with resistance to apoptosis induced by cytotoxic drugs. These include
      high expression of the bcl-2 oncoprotein and abnormalities of expression of the
      p53 tumour suppressor gene. Furthermore bcl-2 expression was found to be
      unregulated by both exogenous and autocrine GM-CSF suggesting that the documented
      negative prognostic effect of autonomous growth on treatment outcome in AML, is
      in part due to the regulatory effect of autocrine GM-CSF on bcl-2 expression,
      thus protecting cells from apoptosis induced by cytotoxic drug therapy.

PMID- 7719231
TI  - Does the type of BCR/ABL junction predict the survival of patients with Ph1
      positive chronic myeloid leukemia?
AB  - The prognostic value of the site of DNA rearrangement within the M-BCR on
      chromosome 22 or of the type of transcript has been debated in the last years.
      The majority of the studies do not support the hypothesis of a predictive value
      of such molecular parameters. Results coming from a multicentric, prospective
      trial, based on alpha-IFN therapy, seem to indicate a better karyotypic response
      in 3' rearranged patients. The possibility of evoking a cytotoxic immune response
      directed towards peptides originating from each of the different BCR/ABL
      junctions constitute an important challenge for the future.

PMID- 7719232
TI  - Stimulation tests for the bone marrow neutrophil pool in malignancies.
AB  - It has been known for decades that blood neutrophilia occurs after the
      administration of etiocholanolone, adrenocortical steroids, and endotoxins.
      Neutrophil leukocytosis in general may be due to several mechanisms such as
      increased stimulation of the myelopoiesis, increased release from the marrow, a
      shift from the marginated to the circulating pool (demargination), prolongation
      in the peripheral half-life, and decreased migration of neutrophils from the
      blood to the tissue. However, the principal cause of the neutrocytosis for each
      of the above mentioned agents is increased release of neutrophils from the bone
      marrow reserves. Since a sufficient reserve capacity is a prerequisite for
      optimal defenses against infections, the marrow response has been used to
      estimate the dose of chemotherapy expected to be tolerated without life
      threatening neutropenia. However, none of the above "test substances" have gained
      widespread use due to adverse reactions or undesirable effects on neutrophil
      function. Recent progress in biotechnology has developed recombinant human (rh)
      hematopoietic growth factors ready for clinical use. Marrow myelopoiesis is
      stimulated by granulocyte colony-stimulating factor (rhG-CSF) and granulocyte
      macrophage CSF (rhGM-CSF). The immediate effect, however, is mobilization of
      mature neutrophil granulocytes to the blood. Bone marrow cellularity seems to
      influence the neutrophil number mobilized during 24 hours by one subcutaneous
      injection of either rhG-CSF or rhGM-CSF. A recent pilot study has suggested such
      a "24 hour stimulation test" to predict severe neutropenia following cyclic
      chemotherapy. This concept is illustrated by two case reports. The "stimulation
      test" suggests that we may devise strategies to define patient subsets which may
      benefit from prophylactic growth factor administration during cyclic
      chemotherapy.

PMID- 7719233
TI  - Epidemiological and etiological aspects of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are increasingly recognized as a cause of bone
      marrow failure, and are at least as frequent as acute myeloid leukemias. While
      the overall incidence is about 2-4/100,000/year, incidence figures rise steeply
      with age. Incidence rates of 20-30/100,000/year in persons over 70 demonstrate
      that MDS are among the most common hematological neoplasias in this age group.
      However, due to difficulties of diagnosis and classification, patient
      registration in population-based registers is far from complete. As a
      prerequisite for truly representative statistics, future revisions of disease
      classification systems must incorporate MDS as a separate group of disorders. The
      difficulties in conducting epidemiological studies also impede the identification
      of risk factors for the development of MDS. Current knowledge of occupational
      risk factors is also reviewed here. More rapid progress in our understanding of
      MDS may come from recent advances in methodology that have begun to shed some
      light on the cytogenetic and molecular aspects of leukemogenesis in general, and
      MDS in particular. Non-random chromosomal changes can be found in about 50% of
      cases at diagnosis, but they are probably late events in the evolution of MDS,
      reflecting the progressive genomic instability of the premalignant clone. Proto
      oncogene mutations have also been suggested to be relevant to the pathogenesis of
      MDS, but longitudinal studies of point mutations of the N-ras proto-oncogene
      revealed that such events, although often associated with rapid deterioration and
      transformation to AML, also appear to be late events during the course of
      disease. Therefore, it remains a major challenge to identify those lesions that
      initiate the multistep development of preleukemia. As the incidence of MDS
      correlates strongly with age, it is reasonable to presume that age-dependent
      changes of the hematopoietic system may play a role in the initiation of MDS.
      Aging is probably associated with a compromised marrow reserve through reduction
      in the size of the stem cell pool. Through increased proliferative activity, the
      remaining stem cells may be particularly vulnerable to mutagenic insults.
      Immunological attack on stem cells, mitochondrial DNA mutations, and the
      regulatory influence of the hematopoietic microenvironment must also be
      considered as possibly contributing to the early stages of MDS.

PMID- 7719234
TI  - De-novo acute myeloid leukemia with trilineage myelodysplasia (AML/TMDS) and
      myelodysplastic remission marrow (AML/MRM).
AB  - Trilineage myelodysplasia (TMDS) in de novo acute myeloid leukemia (AML) at
      initial diagnosis and during remission has not been well recognized yet. In this
      review we describe the characteristics of de novo AML with TMDS (AML/TMDS) and
      with myelodysplastic remission marrow (AML/MRM) in view of the in vivo and in
      vitro disease progression. AML/TMDS was found in ten (10.4%) of 96 patients with
      de novo AML at initial diagnosis and AML/MRM were also observed in three (5.0%)
      out of 60 cases in remission after chemotherapy in our hospital between 1984 and
      1992. Abnormal karyotypes were seen in six of nine AML/TMDS patients and all of
      the three AML/MRM. Karyotypic changes occurred in two of AML/TMDS and two of
      AML/MRM during their clinical course. Using the long term bone marrow culture
      (LTBMC) system that allowed abnormal clones to survive preferentially to the
      clone of normal karyotype, latent clones were detected in three patients with
      AML/TMDS and three of AML/MRM as in the cases of myelodysplastic syndrome (MDS)
      and AML transformed from MDS (MDS/AML) but not in the typical AML without
      myelodysplastic changes. Four of these cases exhibited the same karyotypes as
      seen during the clinical course. Primary abnormal karyotypes prior to clonal
      evolution were also observed in two of the AML/MRM. Taken together, both AML/TMDS
      and AML/MRM are similar to MDS/AML with respect to their myelodysplastic
      background and potential for disease progression and may have progressed to AML
      from the preceding disease status more rapidly than MDS/AML.

PMID- 7719235
TI  - Interleukin-2 bolus infusion as late consolidation therapy in 2nd remission of
      acute myeloblastic leukemia.
AB  - The activation of autologous cytotoxic cells by interleukin-2 (IL-2) may be a
      promising tool for elimination of minimal residual blast populations in patients
      with acute myelocytic leukemia (AML) to prolong disease-free survival. Here, we
      report the results of a phase II study using IL-2 for consolidation therapy in
      patients with second remission of de novo AML. All patients in 1st relapse of AML
      received a uniform induction therapy consisting of intermediate high-dose AraC
      (iHDAraC) 2 x 600 mg/m2 d1-4 and VP-16 100 mg/m2 d1-7. Patients achieving 2nd
      remission were treated with 4 cycles recombinant IL-2 (rIL-2) 9 x 10(6) IU/m2
      administered on d1-5 and 8-12/cycle as 1h infusion every six weeks. In 37/66
      (56%) evaluable patients, complete remission (CR) was achieved. So far, 21/37
      patients (4 after additional autologous bone marrow transplantation (ABMT)
      received rIL-2 consolidation. Three patients are too early for evaluation, 4
      received allogeneic BMT, 6 relapsed before IL-2 was scheduled and 4 refused
      treatment with rIL-2. The median disease-free survival (DFS) was 11 (4-49+)
      months. Up to now, in 5/21 (24%) patients the duration of 2nd remission exceeded
      that of 1st remission 7/21 (33%) are in ongoing 2nd remission (7+ to 49+ months).
      The side effects of rIL-2 were generally moderate and manageable. Only in two
      patients, previously treated with ABMT, severe side effects occurred; septicaemia
      and pneumonia in one patient and desquamative erythrodermia in the second one. In
      accordance with other studies rebound lymphocytosis with a marked increase of
      CD56(+)-cells and release of secondary cytokines such as TNF-alpha, IFN-gamma and
      IL-6 was observed. The schedule is feasible and the data suggest a possible
      benefit for DFS, which, however has to be confirmed by randomized trials.

PMID- 7719236
TI  - Molecular analysis of CD2 gene expression in acute myeloblastic leukemia
      expressing T-lineage associated surface antigens.
AB  - CD2 is a surface marker of T cells and NK cells, and is not normally expressed on
      human myeloid cells, but is found on a significant minority of cases of acute
      myeloid leukemia (AML). Molecular studies were performed on bone marrow
      myeloblasts from two patients with CD2 surface positive AML. No abnormality of
      the CD2 gene was detected on Southern blot analysis. On Northern blots, CD2 mRNA
      of normal size was present. The CD2 gene contained a site which was unmethylated,
      consistent with active transcription, in a CD2 positive AML case, and in a CD2
      positive T cell line, but methylated in CD2 negative AML cells. The evidence does
      not support the hypothesis that inappropriate surface expression of lineage
      markers is due to leukemia-related genetic changes, such as amplification or
      rearrangement, of the CD2 gene itself. Rather, the results are consistent with
      the hypothesis that mixed lineage leukaemia arises from rare normal bone marrow
      progenitors with multilineage phenotypes.

PMID- 7719237
TI  - Acute promyelocytic leukaemia cells resistant to retinoic acid show further
      perturbation of the RAR alpha signal transduction system.
AB  - Acute promyelocytic leukaemia (APL) cell lines resistant to all-trans retinoic
      acid (ATRA) have been previously derived from the NB4 cell line, and
      characterized as having lost the expression of the intact pml/RAR alpha fusion
      protein. To confirm the association between ATRA-resistance and alteration in the
      fusion protein at the clonal level, 16 clones were generated from ATRA-resistant
      APL cell lines. All clones show immunological (HLA class I and II, CD11b and c,
      CD13 and 33), molecular and growth features similar to the parental cell lines.
      To investigate whether the irradiation protocol used to generate the previously
      reported retinoic acid-resistant NB4.306 cell line induced additional alterations
      that could render these cells able to escape the anti-proliferative effect of
      retinoic acid (ATRA), an additional ATRA-resistant APL cell line, [NB4.007/6],
      was generated, under the selective pressure of ATRA, from the NB4 cell line
      without previous radiation. This cell line shows resistance to the anti
      proliferative and differentiating action of ATRA. The NB4.007/6 cell line
      contains the t(15;17) chromosome translocation, shows the usual pml/RAR alpha
      hybrid DNA but expresses no detectable amount of the usual pml/RAR alpha protein
      in Western blot analysis, similarly to the NB4.306 cell line. Finally, the
      relative resistance to ATRA of NB4.306 and NB4.007/6 was evaluated by comparing
      the phenotypic (CD11b) changes induced by ATRA in these two lines with those
      induced in the parental, ATRA-sensitive, NB4 cell line. It is estimated that
      NB4.306 and NB4.007/6 are about 300 and 70 times less sensitive to ATRA than the
      original NB4 cell line.

PMID- 7719238
TI  - Immunophenotypic and DNA genotypic analysis of T-cell and NK-cell subpopulations
      in patients with B-cell chronic lymphocytic leukaemia (B-CLL).
AB  - Absolute numbers and distributions of peripheral blood T-cells and NK cells were
      immunophenotypically determined in 21 patients with B-CLL and compared with those
      obtained from a series of 13 elderly normal controls with an age range of 60-87
      years. For absolute CD3+, CD4+ and CD8+ T-cell, and CD16+ NK subpopulation
      numbers, there were no consistent differences between the normal and B-CLL groups
      although some individual patient variation was seen. Immunophenotypic analyses
      did however reveal that CD3+ T-cells in almost half (10/21) of the B-CLL patients
      were Ia+ (defined as > 20% positive cells), compared to 0/13 of the elderly
      control group (p < 0.001), and that the proportions of CD4+ and CD8+ cells
      expressing membrane CD45RO were significantly increased compared to the control
      group. Subdivision of the B-CLL cases into those with low (< 20%) and high (>
      20%) proportions of CD3+ T-cells co-expressing Ia further showed that CD45RO
      expression by CD4+ fractions was particularly prominent in the Ia+ subgroup, and
      that the relative increase of CD4+CD45RO+ cells was primarily a consequence of
      decreased absolute numbers of CD4+CD45RA+ lymphocytes. This study also examined
      extracted DNA from enriched CD3+ T-cell fractions (obtained by immunomagnetic
      bead selection in 9 of the B-CLL cases) by PCR analysis with two primers for the
      T-cell gamma gene locus. With the V gamma C (consensus) primer, 8/9 cases were
      polyclonal and the remaining case was oligoclonal. For comparison, 7/9 CD3+
      fractions were oligoclonal with the V gamma 9 primer with the other two cases
      being polyclonal. No monoclonal CD3+ components were found. It is suggested that
      the observed increased Ia expression by CD3+ cells and the predominance of CD4+
      cells expressing membrane CD45RO in patients with B-CLL may be of potential
      relevance to understanding the pathogenesis and patterns of disease progression.

PMID- 7719239
TI  - Usefulness of immunocytochemistry for phenotypical analysis of acute leukemia;
      improved fixation procedure and comparative study with flow cytometry.
AB  - We investigated the phenotypes of blast cells of 53 patients with acute leukemia
      by a modified streptavidin-biotin alkaline phosphatase (SAB-AP) labeling
      technique, using a panel of monoclonal antibodies [MoAb; anti-CD11b, CD13, CD14,
      CD33, CD34, CD41, CD3, CD7, CD10, CD19, anti-HLA-DR, and anti-myeloperoxidase
      (MPO)]. The selection of an optimal fixative solution for each antigen from five
      options of various combinations of formalin, acetone, methanol, and/or ethanol,
      successfully conserved cell morphology and improved specific reaction compared
      with the conventional methods which used a single fixative for multiple antigens.
      We compared the SAB-AP results with those obtained by flow cytometry (FCM) for
      surface markers in each case. High concordance rates for both positive and
      negative results were observed for each marker. However, positive reaction for
      some markers (anti-CD13, CD14, CD33, and CD34) were often noted only in the
      cytoplasm by the SAB-AP method, indicating that combination of these two methods
      is essential for the precise immunophenotyping of poorly differentiated leukemia
      cells.

PMID- 7719240
TI  - Recombinant interferon alpha 2a, thymopentin and low doses of cytosine
      arabinoside for the treatment of myelodysplastic syndromes: a pilot study.
AB  - Eighteen patients (pts) with myelodysplastic syndrome (MDS) were treated with
      thymopentin (TP) (50 mg subcutaneously for 5 days) and recombinant interferon
      alpha 2a (rIFN alpha 2a) (3 MU/m2 subcutaneously on the sixth day); the courses
      were delivered every week. Moreover those pts with > or = 10% blasts in the bone
      marrow were additionally treated with low dose cytosine arabinoside (LDARAc) (20
      mg standard dose, subcutaneously, twice a day for seven days every four weeks).
      Sixteen pts were finally assessable for response. Seven pts (44%) were classified
      as good responders, 5 (31%) had a PR; the overall response rate (GR+PR) was 75%.
      Two pts (12.5%) showed stable disease and the 2 remaining (12.5%) had progressive
      disease. Six pts with an initial moderate anemia never required supportive care
      before and during the therapy; in contrast to 10 pts who were transfusion
      dependent. After six months of therapy 2 pts decreased their transfusional needs
      by 50% (1 of them did not receive any transfusion over the following six months
      of therapy); 2 pts needed no packed red cell infusions and 1 pt decreased his
      transfusional support by 75%. Five pts kept an unchanged supportive care load.
      The overall median survival was 12.5 months. Therapy was generally well tolerated
      with acceptable compliance; the most frequently recorded side effects were
      neutropenia and thrombocytopenia grade 2-3 among the group receiving LDARAc.
      However no life-threatening infectious episodes or bleeding were observed. TP,
      rIFN alpha 2a and LDARAc can be safely administered on an outpatient basis to MDS
      pts and appears to have significant activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719241
TI  - HIV-associated lymphoma of the gastrointestinal tract: the University of Toronto
      AIDS-Lymphoma Study Group experience.
AB  - We present a retrospective analysis of 31 (30 male) patients with HIV-associated
      gastrointestinal lymphoma which was undertaken to determine the natural history
      and response to therapy. Only seven patients had stage I or II lymphoma and 22
      had stage IV. Pathology included diffuse large cell (13), immunoblastic (10), and
      small cell non-cleaved (7). The median age at presentation was 39 years (range 24
      59), and the median CD4 count before treatment was 100/microL (range 4-1150).
      Eighty-seven percent of patients received systemic chemotherapy and significant
      response was seen in 84% (CR 38%; PR 46%). Hematologic toxicity was high (febrile
      neutropenia in 44% and dose reductions were required in 81%) and perforation
      occurred in five patients. Median survival for all patients was 6 months and
      death was secondary to lymphoma in 61%, treatment toxicity in 10%, other AIDS
      related illnesses in 25% and other causes in 4%. Survival was shorter for
      patients with bone marrow involvement and for those with poor performance status.
      HIV-associated GI lymphoma has a poor prognosis despite good initial response to
      chemotherapy and is associated with a higher perforation rate than in HIV
      negative patients.

PMID- 7719242
TI  - Sequential phenotyping of myeloma patients on chemotherapy: persistence of
      activated T-cells and natural killer cells.
AB  - To better detail the status of functional T cell subsets and natural killer cells
      in multiple myeloma, we undertook a detailed immunophenotypic study of
      circulating mononuclear cells in myeloma. We studied myeloma patients entered on
      a large prospective, randomized ECOG chemotherapy trial EST 9486 for patients
      with newly diagnosed multiple myeloma. All patients were studied prior to entry
      and then two months after initiation of therapy (e.g. post two cycles of
      Vincristine, BCNU, melphalan, cyclophosphamide and prednisone (VBMCP)). The
      chemotherapy protocol was a three-arm protocol utilizing either VBMCP, VBMCP
      alternating with interferon, or VBMCP with intermittent high dose
      cyclophosphamide. The major findings in this analysis include significant
      reductions in the white blood cell count, total lymphocytes, T cell (CD3+), T
      helper (CD4+), and T suppressor (CD8+) cells, after 2 cycles of VBMCP. However,
      there was a relative sparing of Natural killer (CD16+) and activated T cell
      (CD2+, HLADR+) reduction in these same patients. In summary, only two cycles of
      combination chemotherapy resulted in significant reductions in white blood cell
      and lymphocyte counts in multiple myeloma patients. All cell types appear to have
      been reduced by chemotherapy except for activated T cells and natural killer
      cells. The impact of selective modulation of functional T cells subsets during
      therapy for patients with multiple myeloma is an important parameter which needs
      to be addressed in the overall approach to these patients.

PMID- 7719243
TI  - Clinical significance of serial measurement of the serum levels of soluble
      interleukin-2 receptor and soluble CD8 in malignant lymphoma.
AB  - We serially measured the serum levels of soluble interleukin-2 receptor (sIL-2R)
      and soluble CD8 (sCD8) in 36 patients with malignant lymphoma (33 non-Hodgkin's
      lymphoma cases and three Hodgkin's disease cases). The level of serum sIL-2R was
      significantly elevated in patients with active disease (18) compared to those in
      remission (18), and correlated with the clinical stage of the lymphoma. The
      temporal profile of the sIL-2R level reliably represented the disease status,
      which was judged clinically, during the course of the disease. In three patients,
      the tumor bulk paralleled the sIL-2R level. On the other hand, a less significant
      correlation was found between the serum sCD8 level and disease activity. The
      serial measurement of sCD8 appeared to be less useful for monitoring the disease
      activity, although there was a significant correlation between the sCD8 and sIL
      2R levels. This study indicates that serial measurement of the serum sIL-2R level
      may be useful for monitoring the tumor burden in response to treatment and for
      early detection of disease progression in malignant lymphoma.

PMID- 7719244
TI  - Chronic lymphoid leukemias: recent advances in biology and therapy.
AB  - There exists a wide variety of lymphoid leukemias derived from B and T
      lymphocytes. These diseases have distinct immunologic and biologic features as
      well as varied responses to therapeutics. The most common lymphoid leukemia is
      chronic lymphocytic leukemia (CLL) which is a clonal proliferation of a subset of
      B cells expressing the CD5 antigen. Prolymphocytic leukemia is usually derived
      from B cells and shares some features with CLL but is clearly a distinct entity.
      Hairy-cell leukemia is a B cell malignancy that is uniquely responsive to a
      variety of biologic and chemotherapeutic agents. Waldenstrom's macroglobulinemia
      is a B cell malignancy that secretes immunoglobulin M (IgM) and may present with
      the hyperviscosity syndrome. Other B cell malignancies that less commonly present
      as leukemias include non-Hodgkin's lymphomas such as follicular lymphoma or
      mantle zone lymphoma. Multiple myeloma may rarely present or evolve into a plasma
      cell leukemia, typically in far advanced disease. T cell malignancies that may
      present as chronic lymphoid leukemias, and in the past have often been referred
      to as T cell chronic lymphocytic leukemia, are large granular lymphocytic
      leukemia, adult T cell leukemia/lymphoma, Sezary cell leukemia and rare cases of
      non-Hodgkin's lymphoma that are T cell derived and may present or evolve into a
      leukemic phase. There is also a rare T cell counterpart of prolymphocytic
      leukemia. Distinguishing these diseases is critical for optimal care of these
      patients.

PMID- 7719245
TI  - Acute promyelocytic leukemia: from clinic to molecular biology.
AB  - Acute promyelocytic leukemia (APL) is a good model for studying the human
      malignancies in that up to 90% of APL patients can achieve complete remission
      (CR) with a differentiation inducer, all-trans retinoic acid (ATRA). APL is also
      associated with a specific chromosomal translocation t(15;17) which fuses the
      retinoic acid receptor alpha (RAR alpha) gene with a chromosome 15q locus, PML.
      Recently the RAR alpha and the PML gene structural alterations in t(15;17) have
      been characterized. The heterogeneity of the PML rearrangements juxtaposes
      different PML gene portions to the same set of RAR alpha exons, producing two
      major PML-RAR alpha fusion mRNA isoforms. A retrotranscriptase/polymerase chain
      reaction (RT-PCR) analysis of the fusion transcripts has been developed which
      allows the detection of minimal residual disease during the clinical remission of
      APL. Molecular study showed PML-RAR alpha can form heterodimers with wild-type
      PML and RXR. Recently, PML has been shown to be one of the components of a
      nuclear body, POD. In APL, the normal organization of POD is disrupted by PML-RAR
      alpha, whereas ATRA treatment in vivo and in vitro can induce a reorganization of
      this organelle. Cytogenetic and molecular study allowed a variant translocation
      t(11;17) being recently discovered in a small subset of APL. This time RAR alpha
      is fused to a new gene, PLZF, on chromosome 11q23. It has been shown that the
      PLZF-RAR alpha, like PML-RAR alpha, has a "dominant negative" effect on the wild
      type RAR-RXR. Clinical data obtained from a group of t(11;17) APL patients showed
      that these respond poorly to ATRA and could be grouped in a special clinical
      syndrome within APL. The comparison of the biological activities mediated by PML
      RAR alpha and PLZF-RAR alpha may give new insights into the pathogenesis as well
      as the mechanisms of ATRA-induced differentiation in APL.

PMID- 7719246
TI  - Pathogenesis of the anemia of chronic disease: a cytokine-mediated anemia.
AB  - The anemia found in patients with chronic infectious, inflammatory and neoplastic
      disorders, known as the anemia of chronic disease (ACD), is one of the most
      common syndromes in medicine. A characteristic finding of the disorders
      associated with ACD is increased production of the cytokines which mediate the
      immune or inflammatory response, such as tumor necrosis factor, interleukin 1 and
      the interferons. All the processes involved in the development of ACD can be
      attributed to these cytokines, including shortened red cell survival, blunted
      erythropoietin response to anemia, impaired erythroid colony formation in
      response to erythropoietin and abnormal mobilization of reticuloendothelial iron
      stores. Improved understanding of the role played by cytokines in the
      pathogenesis of ACD may lead to the development of more specific therapy for this
      syndrome.

PMID- 7719247
TI  - Dynamic regulation of integrins.
AB  - Dynamic regulation of receptor function is a distinguishing feature of the
      integrin family of adhesion molecules and makes a significant contribution to
      alterations in cellular adhesive properties. The best characterized example is
      that of the platelet receptor alpha IIb beta 3 (glycoprotein IIb-IIIa), which
      does not bind soluble fibrinogen on resting platelets. Following platelet
      activation, the alpha IIb beta 3 binds soluble fibrinogen with moderately high
      affinity and platelet aggregation ensues. Similar regulation of receptor function
      has also been directly demonstrated for alpha 5 beta 1 and alpha M beta 2, and it
      is likely that it is a general property of all members of the family. The altered
      ligand binding affinity is due to a change in the conformation of the external
      domain of the receptor, in response to intracellular signals that are transmitted
      the length of the molecule. The cytoplasmic tails of the integrins are active
      participants in this regulation, and they also mediate interactions with the
      cytoskeleton. A number of anti-integrin monoclonal antibodies have been described
      which induce high affinity ligand binding, and certain of these preferentially
      bind to the high affinity conformation of the receptor. The alteration in
      conformation allows better access for macromolecular ligands to the ligand
      binding pocket, which has been mapped (in alpha IIb beta 3) to the amino terminal
      globular head of the receptor. The precise mechanism by which the activating
      signal is transferred from within the cell to the distal external domain remains
      the subject of active research.

PMID- 7719248
TI  - A newly established megakaryoblastic/erythroid cell line that differentiates to
      red cells in the presence of erythropoietin and produces platelet-like particles.
AB  - In August, 1992, we established a leukemic cell line (NS-Meg) from a patient in
      megakaryoblastic transformation of Philadelphia chromosome-positive chronic
      myeloid leukemia. The NS-Meg cells were positive for alpha-naphthyl acetate
      esterase and periodic acid-Schiff (PAS) staining and for surface CD4, CD7, CD13,
      CD34, CD41a, and glycophorin A antigens. Ultrastructurally, the cells had alpha
      granules, demarcation membranes, and platelet peroxidase activity. The NS-Meg
      cells spontaneously produced platelet-like particles which contained alpha
      granules, mitochondria and dense bodies, strongly suggesting platelet production.
      Erythropoietin (Epo), granulocyte/macrophage colony stimulating factor(GM-CSF),
      and interleukin 3 (IL-3) promoted the growth of NS-Meg cells. Phorbol-12
      myristate-13-acetate increased the expression of both CD41a and CD61 antigens.
      Ten-day exposure to Epo induced mature erythroblasts and red cells. These
      benzidine-positive cells were positive for hemoglobin F staining. Untreated NS
      Meg cells expressed mRNA for the Epo receptor (EpoR), for GATA-1, and for alpha
      1, alpha 2 and gamma globin genes. These results indicate that NS-Meg cells
      undergo terminal differentiation of both megakaryocytic and erythroid lineages.
      This cell line should be a very useful tool for the investigation of both
      megakaryocytic and erythroid maturation.

PMID- 7719249
TI  - Lack of a correlation between p53 protein expression and radiation response in
      human tumor primary cultures.
AB  - We investigated the possible relationship between immunohistochemically detected
      p53 expression and in vitro response to gamma-irradiation in 24 primary cultures
      of human ovarian cancers and cutaneous melanomas. The frequency of p53-positive
      tumors was around 60% within each tumor histotype. The range of the surviving
      fraction at 2 Gy (SF2) was similar in p53-positive (0.10-0.76) and p53-negative
      (0.23-0.65) tumors, with median values of 0.36 and 0.33, respectively. No
      differences were observed in the accumulation of DNA-double strand breaks,
      assessed by neutral filter elution after exposure to 50 Gy, between p53-positive
      and p53-negative tumors. As regards DNA lesion repair, after 2 h of recovery the
      percentage of rejoined DNA-double strand breaks ranged from 19% to 99% in the
      different cultures, but again the distribution of values was similar for p53
      positive and p53-negative tumors. Specifically, the median percentage of repaired
      DNA-double strand breaks was 70% and 74% in the two groups. On the whole, our
      data do not support the hypothesis that p53 overexpression is a major determinant
      of in vitro radiation response.

PMID- 7719251
TI  - [Expression in bacteria and some properties of p65, a homolog of cellular heat
      shock proteins HSP70 coded in the RNA of the beet yellows virus genome].

PMID- 7719250
TI  - [Phosphorylation of the rsCD4 receptor in the presence of human blood cells and
      plasma].

PMID- 7719252
TI  - [Mechanisms of integral behavior of the simplest unicellular organisms].

PMID- 7719254
TI  - [The immune system in atopic asthma].

PMID- 7719253
TI  - [Specifics of the water-salt balance in rats breathing various mixtures under
      increased pressure].

PMID- 7719255
TI  - [Test for efficacy of cetirizine and loratadine as a treatment for seasonal
      allergic rhinitis in a 6 week cross-over comparative study].
AB  - Cetirizine and loratadine-two new antihistaminic drugs were evaluated in 56
      patients with seasonal rhinitis in cross-over open study. I our study, no
      difference between loratadine and cetirizine has been seen. Both evaluated drugs
      significantly inhibited the symptoms of allergic rhinitis and conjunctivitis.
      Adverse reaction and inhibition of histamine and codeine skin tests were similar.

PMID- 7719256
TI  - [Correlation between symptoms and results of rhinomanometric measurements of
      nasal patency in patients with seasonal allergic rhinitis].
AB  - The aim of presented study were to assess the usefulness of rhinomanometry in
      monitoring course of disease and effectivity of treatment in seasonal allergic
      rhinitis (SAR) through answering the question whether and eventually which
      relationship exists between patient's general feeling and results of
      rhinomanometric measurements of nasal patency (NP). The study involved 114
      subjects with SAR divided into 3 groups dependent on phase of disease and
      severity of complaints and 30 healthy volunteers. For results see table I. Nasal
      flow and resistance measured at differential pressure 75 Pa in groups I, III and
      IV did not differ significantly. In group II nasal flow values were lower (alpha
      < 0.001) and resistance values higher (alpha < 0.001) as compared with remaining
      groups. Thus, the beginning of symptoms is related to lowering of NP as compared
      with symptom-free phase of SAR. In the symptom-free period NP do not differ from
      healthy population. The results of rhinomanometric measurements of NP are useful
      in monitoring of course of SAR in assessment of effectivity of treatment.

PMID- 7719258
TI  - [Granulocyte chemiluminescence during early and late asthmatic reaction].
AB  - Allergic asthmatic patients were challenged with specific allergen resulting in
      early and dual asthmatic reaction. FMLP induced granulocyte chemiluminescence was
      measured before and in 10 min, 60 min, 4 hours and 24 hours after allergen
      challenge. We have observed significant decrease of granulocyte chemiluminescence
      in both groups. In patient with early asthmatic reaction decrease of luminescence
      was observed during first hour only. In patients with dual asthmatic reaction
      decrease of luminescence was observed during 24 hours after allergen challenge.

PMID- 7719257
TI  - [Allergy to nuts and allergy to birch].
AB  - Among 527 children and young in age from 2 months to 19 years of life it has been
      separated the group 70 with increased specific IgE levels to hazelnuts or/and to
      peanuts. In them it has been determined specific IgE to pollen birch and it has
      been make correlation the results with the symptoms. Specific IgE has been
      determined immunoenzymatic Visagnost Tosse Diagnostika method. The control group
      stand 34 children in the same age with the infections symptoms. In the infants
      group--13 (59.1%) had sIgE to birch, in children 2-3 age group--15 (75%), in 406
      age--8 (72.7%), in the school age--7 (87.5%) and in young > 16 age--8 (88.9%). In
      the control group found absence sIgE to each of examination allergens. In 5
      infants in the time of the pollen birch (April 1993) it has been manifestation
      dyspnoea. In group 2-3 age--in 10 (45.5%) found pollinosis symptoms, 12 (60%) had
      asthmatic dyspnoea, 7 (35%) atopic dermatitis, 2 (10%) allergic
      rhinoconjunctivitis and 5 (25%) abdominal pain with concomitant dyspnoea. It has
      been characteristic, that never found one of clinical allergic symptoms. In group
      5-6 age and 7-15 age it has been dominated atopic dermatitis (63.3% and 87.5%),
      pollen asthma (45.4% and 62.5%) and pollinosis (45.4% and 25%). While in young 16
      age--8 (88.8%) had pollinosis, 5 (55.5%) had atopic dermatitis and pollinosis.
      THE CONCLUSION: 1. In children which had specific IgE to nuts increased together
      with age specific IgE to birch. 2. The gravely pollinosis symptoms appear in
      small children in 1-2 age of life, already.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719259
TI  - [Behavior of some parameters of the autonomic nervous system in patients with
      bronchial asthma].
AB  - It is well known that beta receptors play a crucial role in maintaining tonus of
      smooth muscles of the airways. In this study the authors have indirectly assessed
      the beta receptor performance by measuring serum cAMP levels before and after
      intravenous administration of Salbutamol. Parallelly the activity of the
      parasympathetic system was analysed. The observed increases of serum cAMP
      dependent on different duration of the disease. The age of the patients did not
      affect the observations. These results may imply that disturbances of beta-2
      receptors function are acquired in patients with bronchial asthma.

PMID- 7719260
TI  - [The effect of inhaling pirenzepine--selective M1 receptor antagonist and
      ipratropium bromide on lung ventilation in patients with bronchial asthma].
AB  - The study was carried out on 19 patients with moderate and severe bronchial
      asthma. During three days after the initial spirometric evaluation the patients
      received--on the first day 0.5 mg of pirenzepine in nebulization (P), on the
      second day 0.25 mg of ipratropium bromide (IB), on the third day both substances
      together. Ventilatory parameters were monitored on the 5th, 20th, 40th and 60th
      minute following nebulization. The observed parameters did not differ
      significantly between both groups. Pirenzepine given after ipratropium bromide
      increased FEV1 from 1.89 L to 2.37 L (p < 0.01). The observed results imply that
      pirenzepine given with ipratropium bromide induce a significant bronchodilating
      effect and could be added to therapy of bronchial asthma.

PMID- 7719261
TI  - [Evaluation of the bronchodilatory activity of berodual and its components:
      fenoterol and ipratropium bromide in children with bronchial asthma].
AB  - The bronchodilatory activity of Berodual in comparison to Fenoterol and
      Ipratropium Bromide was investigated in a group of 59 children aged 8-15 years,
      suffering from mild bronchial asthma in a symptoms-free period. The relaxing
      activity was monitored dynamically by means of the analysis of flow-volume curve
      measurements. We have found that the bronchodilatory activity of Berodual was
      faster, stronger and longer in comparison to Fenoterol and Ipratropium Bromide.

PMID- 7719262
TI  - [Effect of bronchoalveolar lavage (BAL) on gasometric and spirometric parameters
      in patients with sarcoidosis].
AB  - The effect of BAL and fiberoptic bronchoscopy on gasometric and spirometric
      parameters was studied in 22 patients with sarcoidosis and 15 volunteers. In 12
      patients with sarcoidosis during the repeated BAL procedure the effect of oxygen
      supplementation (by nasal prongs 3 L/min) was analysed. Significant decrease of
      oxygen pressure (PaO2) and vital capacity was seen in patients undergoing BAL and
      fiberoptic bronchoscopy. The administration of oxygen during the BAL procedure
      prevented the fall in oxygen pressured.

PMID- 7719263
TI  - [The influence of vitamin A on production of oxygen free radicals and activity of
      granulocyte catalase in patients with chronic bronchitis].
AB  - The effect of vitamin A on granulocyte chemiluminescence (CT) and catalase
      activity was studied in 16 patients with COPD. The results obtained show a
      significant decrease of CL and a significant increase of granulocyte CT activity
      after incubation with vitamin A, particularly in nonsmoking subjects. This study
      showed a significant decrease of CT activity after incubation of granulocyte with
      hydralazine both in cigarette smokers or nonsmokers.

PMID- 7719264
TI  - [Pulmonary arteriovenous fistulas].
AB  - Pulmonary arteriovenous fistulas are rare congenital malformations associated in
      40% of cases with Osler-Weber-Rendu disease. PAF acquired in connection with the
      chest trauma, surgery and some inflammatory or neoplastic lung diseases were also
      described. In the Institute of Tuberculosis and Chest Diseases we have observed
      11 cases of congenital PAF in 4000 resected lungs during the last years. In this
      report we described one more case with PAF. A 40 years old man was admitted to
      the Institute of Tuberculosis and Chest Diseases with hemoptysis. History and
      physical examination was unremarkable. Chest roentgenogram revealed a right upper
      lobe infiltrate. Tuberculosis or cancer was suspected and during the diagnostic
      procedures antituberculous drugs were given. After 3 weeks of treatment
      hemoptysis increased and chest roentgenogram revealed progression of the
      infiltrate in the right upper lobe and new lesions in the middle lobe. According
      to the character of X-ray progression which night be characteristic of active
      bleeding, a possibility of arteriovenous fistulas could not be excluded. As life
      threatening haemorrhage persisted right upper lobectomy without angiography was
      done. In the resected lobe arteriovenous fistulas were found. Angiography after
      operation was proposed but was refused by the patient. He is now well and
      symptoms free 5 months.

PMID- 7719265
TI  - [Nasal airflow and its objective evaluation].

PMID- 7719266
TI  - [The role of eosinophilic proteins in bronchial asthma and other respiratory
      diseases].

PMID- 7719267
TI  - [Low molecular weight compound asthma].

PMID- 7719268
TI  - [Principles of mechanical ventilation in status asthmaticus].

PMID- 7719269
TI  - [Intravascular oxygenation--future treatment of respiratory failure].

PMID- 7719270
TI  - [The role of oxidants in the pathology of respiratory diseases].

PMID- 7719271
TI  - [5th anniversary meeting of the Polish Society of Allergology. Warsaw, 13-16
      October 1994. Abstracts].

PMID- 7719274
TI  - A rapid method to estimate the incidence rate and prevalence of insulin-dependent
      diabetes mellitus in children 0-19 years of age.
AB  - OBJECTIVE: To trace new cases of insulin-dependent diabetes mellitus (IDDM) on an
      ongoing basis and to estimate the incidence rate and prevalence of IDDM in
      children 0-19 years of age. RESEARCH DESIGN AND METHODS: The estimation of the
      prevalence and incidence rate of IDDM was based on, respectively, the prevalence
      and the rate of new users of insulin. The data were obtained from pharmacy,
      patient-based, drug dispensing histories in a well-defined population
      encompassing 257,113 individuals in the Netherlands. RESULTS: The IDDM incidence
      rate was estimated at 11.5 (CI95 6.6-17.8) per 100,000 person years in 1989-1990
      in children 0-19 years of age. The prevalence was estimated at 11.0 (CI95 8.6
      13.4) per 10,000 children 0-19 years of age. DISCUSSION: The incidence rate is
      comparable to that found in a large, national survey among all paediatricians and
      internists in the Netherlands. The method offers ongoing monitoring of the
      incidence and prevalence of IDDM in children, 0-19 years of age, against low
      costs. The method is suitable for rapid and cost-efficient recruitment of cohorts
      of incident IDDM patients, which fosters research to identify and quantify the
      attribution of different types of aetiologic and prognostic factors of IDDM.

PMID- 7719273
TI  - Selective digestive decontamination in multiple trauma patients: cost and
      efficacy.
AB  - A double-blind randomized placebo-controlled study was carried out to evaluate
      the efficacy and the cost of selective digestive decontamination (SDD) to prevent
      nosocomial pneumonia in multiple-trauma patients. Nosocomial infections,
      particularly pneumonia, were more frequent in the placebo group. The most common
      infectious agent was Staphylococcus: Staphylococcus aureus in the placebo group
      and Staphylococcus epidermidis in the SDD group. Methicillin-resistant
      Staphylococcus epidermidis was detected more often in the SDD group. No
      methicillin-resistant Staphylococcus aureus was observed in this study. Fewer
      patients in the SDD group required antibiotherapy. SDD resulted in a saving of
      about 41% in drug expenditure.

PMID- 7719272
TI  - Liposomes as delivery systems in the prevention and treatment of infectious
      diseases.
AB  - Research on the potential application of liposomes in the prevention and
      treatment of infectious diseases has focussed on improvement of the therapeutic
      index of antimicrobial drugs and immunomodulators and on stimulation of the
      immune response to otherwise weak antigens in vaccines composed of purified micro
      organism subunits. In this review current approaches in this field are outlined.
      The improved therapeutic index of antimicrobial drugs after encapsulation in
      liposomes is a result of enhanced drug delivery to infected tissue or infected
      cells and/or a reduction of drug toxicity of potentially toxic antibiotics.
      Liposomal encapsulation of immunomodulators that activate macrophages aims at
      reducing the toxicity of these agents and targeting them to the cells of the
      mononuclear phagocyte system in order to increase the nonspecific resistance of
      the host against infections. Studies on the immunogenicity of liposomal antigens
      have demonstrated that liposomes can potentiate the humoral and cell mediated
      immunity to a variety of antigens.

PMID- 7719275
TI  - Information on drug use in the elderly: a comparison of pharmacy, general
      practitioner and patient data.
AB  - Management of pharmacotherapy by the pharmacist and the general practitioner can
      be a difficult task in elderly patients in whom there is a high concomitant, long
      term drug use. Adequate information on drug use is essential in managing
      pharmacotherapy as well as in an accurate assessment of drug exposure in
      pharmacoepidemiologic studies. In this study data from computerized pharmacy
      records, general-practitioner registries and home interviews with 100 elderly
      patients were compared. Pharmacy records contained 80% of all the prescriptions
      found at the home interviews, while in general-practitioner data 40% could be
      traced. Use of drugs dispensed long ago reduced the validity of pharmacy and
      general-practitioner data. Data on analgesics (70% was found) and respiratory
      drugs (68%) were less traceable compared to cardiovascular (83%) and psychotropic
      drugs (81%). Automated pharmacy records are an important source of longitudinal
      data on drug use and will improve the assessment of drug exposure in
      pharmacoepidemiologic studies and optimize pharmaceutical care.

PMID- 7719277
TI  - Some binding properties of the envelope of Porphyromonas gingivalis to
      hemoglobin.
AB  - Porphyromonas gingivalis was found to bind to hemoproteins (hemoglobin,
      myoglobin, catalase, cytochrome c) and the binding properties of the envelope of
      P. gingivalis to hemoglobin were investigated. Maximum amount of hemoglobin bound
      to 1 mg of the envelope was 58 micrograms. No significant binding was observed at
      4 degrees C and the binding was inhibited strongly by tosyl-L-lysine chloromethyl
      ketone, Leupeptin, EDTA and partially by meta-periodate. Heating of the envelope
      at 70 degrees C for 15 min resulted in complete loss of the binding activity. The
      binding activity of the envelope was not influenced by the treatment with the
      endogenous proteases. The envelope saturated with hemoglobin could no longer bind
      to other hemoproteins tested, indicating that binding site for these hemoproteins
      are common.

PMID- 7719276
TI  - Serum antibody response to surface-associated material from periodontopathogenic
      bacteria.
AB  - Saline extracts of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis
      and Eikenella corrodens contain surface-associated components of these bacteria.
      It has been shown that these extracts are potent stimulators of bone resorption
      in vitro. The possibility that the components of these surface-associated
      materials (SAM) could contribute to the serum immune response in patients with
      juvenile or adult onset forms of rapidly progressive periodontitis were
      investigated by direct binding ELISA. Very high titres of serum IgG antibodies to
      SAM from A. actinomycetemcomitans were detected in patients with localized
      juvenile periodontitis (LJP). Patients with adult onset rapidly progressive
      periodontitis (RPP) had significantly raised antibody levels to SAM from P.
      gingivalis. Both groups of patients had significantly raised levels of antibodies
      to SAM from E. corrodens compared with control sera. Thus, not only does
      solubilized SAM have the capacity to induce bone resorption, but it also
      contributes to the antigenic load on the immune system in LJP and RPP.

PMID- 7719278
TI  - An increased number of circulating gamma/delta TCR + T cells in patients with
      chronic viral hepatitis.
AB  - There is evidence that gamma/delta TCR+T cells are specialized in recognizing
      different antigens, but their immunologic role as a second TCR is still unclear.
      The aim of this study was to investigate the percentage of absolute numbers of
      circulating gamma/delta TCR + T cells in patients with chronic viral hepatitis
      (CVH) and to compare with HBsAg+, HCV healthy carriers and healthy subjects.
      Forty nine patients with CVH-24 with chronic active (CAH) and 25 with chronic
      persistent hepatitis (CPH)-, 21 HBsAg+, 20 HCV asymptomatic carriers and 20
      healthy subjects were enrolled in the study. Lymphocyte subsets were determined
      after incubation with monoclonal antibodies to T total (CD5) and T gamma/delta
      cells (TCR-gamma/delta-1) using immunofluorescence microscopy. An increased
      number of circulating gamma/delta TCR + T cells was found in patients with CVH in
      comparison with asymptomatic carriers and normal controls: this increase was more
      profound in patients with CAH, compared to CPH patients. These results indicate a
      correlation between circulating gamma/delta TCR + T cells in CVH patients and
      activity and chronicity of the disease.

PMID- 7719279
TI  - Lipopolysaccharide core region of Hafnia alvei: serological characterization.
AB  - Covalent glycoconjugates containing, as a ligand lipopolysaccharide core,
      oligosaccharides of Hafnia alvei standard strain ATCC 13337 and R mutant 1 M were
      used to produce anti-H. alvei core antibodies. The sera obtained were tested in
      rocket immunoelectrophoresis, immunoblotting and ELISA using H. alvei
      lipopolysaccharides of various strains. The experiments were carried out to study
      the antigenic relationships between lipopolysaccharide core regions in the H.
      alvei genus.

PMID- 7719280
TI  - Serological variety of flagellar antigen H1 in natural Escherichia coli
      population.
AB  - Variation of the Escherichia coli flagellar antigen H1 was studied among 120
      human isolates belonging to more than 25 O:K serovars. Factor-specific antisera
      were prepared and shown to be useful in the identification of serological
      subtypes of H1. The three subtypes found were defined as H1abc, H1acd and H1abe.
      The H1abc corresponded to the standard flagellar antigen H1 present in 84% of all
      strains. It was found in all O groups except O15, O17 and O83. Eight O15 and two
      O17 strains studied were of subtype H1abe, while the one O83 strain studied was
      H1acd. Both subtypes H1abc and H1acd were found among strains within O6:K5,
      O6:K13 or O-non-typeable:K5 serovars.

PMID- 7719281
TI  - A study of pathogenic factors of Streptococcus pneumoniae strains causing
      meningitis.
AB  - Pneumococcal meningitis in St. Petersburg in the period 1985-1991 occurred in 1.7
      2.3 children per 100,000 annually. The most common serotypes among pneumococcal
      strains isolated from patients with meningitis were 19, 1, 6, 15, and 2, whereas,
      among the capsulated strains isolated from carriers, type 3 predominated. Only
      one third of strains from cases of meningitis were highly virulent for mice
      (types 1, 2, 3). Hyaluronidase was produced by all the 39 studied strains, 22
      (84.6 +/- 7.1%) out of 26 strains from patients with otitis media, and only by 15
      (11.5 +/- 2.8%) out of 130 strains isolated from carriers. Non-capsulated strains
      lacked this enzyme. Results of intranasal inoculation of pneumococcal strains
      with different hyaluronidase activity and addition of exogenous hyaluronidase to
      strains which did not produce the enzyme confirm the hypothesis that this enzyme
      plays an important role in bacterial dissemination and breaching of the blood
      brain barrier by pneumococci. It was concluded that high hyaluronidase activity,
      presence of capsule, and pneumolysin or serotype (1, 2, and 19) despite
      hyaluronidase titer, are the most important factors contributing to the
      development of pneumococcal meningitis. The role of the mouse toxic factor is
      unclear.

PMID- 7719282
TI  - Modulation of human polymorphonuclear leukocyte chemotaxis and superoxide anion
      production by Pseudomonas aeruginosa exoproducts, IL-1 beta and piroxicam.
AB  - Whereas addition of 200 ng ml-1 exotoxin A (exoA) did not modify PMNL chemotaxis,
      20 U ml-1 human recombinant interleukin-1 beta (hrIL-1 beta) primed
      polymorphonuclear leukocytes (PMNL) for migration towards Pseudomonas aeruginosa
      peptide chemotactins (PAPCs). Piroxicam (100 micrograms ml-1), a non-steroidal
      anti-inflammatory agent (NSAIA), inhibited PMNL chemotaxis and abolished the
      priming effect of hrIL-1 beta. Both PAPCs and exoA induced PMNL superoxide anion
      production, but neither hrIL-1 beta nor piroxicam modified significantly PMNL
      superoxide anion production induced by PAPCs. The fact that hrIL-1 beta can prime
      PMNL for chemotaxis towards PAPCs and that piroxicam can abolish activation by
      primed PMNL are findings relevant to the pharmacological control of lung tissue
      damage during P. aeruginosa pneumonia.

PMID- 7719283
TI  - Inhibition of saliva-induced oral streptococcal aggregation by blood group
      glycoproteins.
AB  - The inhibition of saliva-induced oral streptococcal aggregation with anti-sera
      (anti-A, anti-B, anti-AB and anti-B treated with galactose), normal human serum
      (NHS), blood group-specific lectins (UEA-I, HBA, GPA, BSI-B4, GS-I), non-specific
      blood group lectins (MPA, SBA) and carbohydrates (galactose, N
      acetylgalactosamine, L-fucose) was studied. Streptococcal species and strains
      included S. mutans 318, S. mutans 10449, S. mutans NG-8, S. salivarius and S.
      cricetus HS-6. The saliva was obtained from three subjects with secretor status
      (2 blood group B persons, 1 blood group A person). The data obtained from
      experiments performed with S. mutans 10449 and S. mutans NG-8 suggest the
      involvement of the H-antigenic determinant in the aggregation mechanism of the
      first strain and of the group B determinant for the second strain. The
      aggregation of S. salivarius only by B saliva might be related to a galactose
      specific lectin on this strain and to some properties of its cell surface
      (hydrophobicity and the fibrillar surface layer). S. cricetus HS-6 aggregation
      was inhibited in different degrees by all the inhibitors used. The results
      demonstrate that interactions between oral streptococci and salivary components
      depend on the strain and species and on the individual saliva samples.

PMID- 7719284
TI  - Functional impairment of rat Kupffer cells induced by aflatoxin B1 and its
      metabolites.
AB  - Contamination of food with mycotoxins is a major health problem. Impairment of
      several immune functions has been repeatedly reported in animals fed with
      contaminated fodder. Since the liver is a major target of toxicity by aflatoxins,
      the effects of aflatoxins B1, and its hepatic metabolites Q1 and M1 on Kupffer
      cell function was investigated in vitro. Aflatoxin B1 induced significant (P <
      0.05) inhibition of phagocytosis, intracellular killing of Candida albicans, and
      intrinsic anti-Herpes virus activity at concentrations as low as 0.01 pg ml-1.
      Aflatoxin Q1 and M1 had similar effects on phagocytosis and microbicidal
      activity, but were two- to ten-fold less potent than aflatoxin B1.

PMID- 7719285
TI  - Lysis of uninfected HIV-1 gp120-coated peripheral blood-derived T lymphocytes by
      monocyte-mediated antibody-dependent cellular cytotoxicity.
AB  - Previous reports from our laboratory have demonstrated that peripheral blood
      monocytes (PBM) from HIV-1 infected individuals are de novo activated and are
      cytotoxic in vitro. Significant monocyte-antibody-dependent cellular cytotoxicity
      (ADCC) was obtained against HIV-1 inactivated CD4+ CEM target cells coated with
      HIV-1 in the presence of autologous seropositive serum. Based on these findings,
      we hypothesized that in HIV-seropositive individuals the monocytes may play an
      important role in vivo in the autodestruction of non-infected CD4+ T lymphocytes.
      The present study was designed to test this hypothesis. Monocytes from normal
      donors activated with M-CSF lysed CD4+ T cells (CEM) coated with gp120 sensitized
      by plasma from asymptomatic HIV-1+ individuals in a 8 h 51Cr release assay. ADCC
      cytotoxic activity varied from one individual to another and was a function of
      the dilution of the individual seropositive plasma used. We then used circulating
      CD3+ T lymphocytes as targets for ADCC following treatment with actinomycin D to
      facilitate the release of radioactive 51Cr. Like CEM, ADCC was obtained with CD3+
      T cells coated with gp120 in the presence of HIV seropositive plasma and
      monocytes. Lysis was specific as T cells that were not coated with gp120 were not
      destroyed. These findings demonstrate that activated peripheral blood derived
      monocytes can destroy non-infected gp120-coated circulating T lymphocytes by an
      ADCC-mediated mechanism. Thus, these findings suggest that ADCC may be one
      mechanism operating in vivo for the destruction of non-infected CD4+ T
      lymphocytes.

PMID- 7719286
TI  - Shigella flexneri-HeLa cell interactions: a putative role for host cell protein
      kinases.
AB  - Epithelial cell invasion has been shown to be a prerequisite for Shigella
      flexneri virulence. Recently, we have documented the induction of transcription
      factor DNA binding activities as a result of S. flexneri challenge of HeLa cells.
      In this report, we show that HeLa cells challenged with S. flexneri display
      differences in phosphotyrosine-containing proteins. These changes are detected as
      early as 5 min post-challenge. Challenge with a noninvasive ipaB mutant strain
      resulted in the induction of a similar, but less intense, profile of
      phosphotyrosine-containing host cell proteins. Phosphotyrosine-containing
      proteins could be detected in S. flexneri, but were unique from those detected
      following HeLa cell challenge. S. flexneri invasion of HeLa cell monolayers was
      reduced by treatment with protein kinase inhibitors. These data suggest a role
      for protein kinases in the initial response of host cells to S. flexneri.

PMID- 7719287
TI  - Binding to fibronectin (FN)--a prerequisite step? Investigations on the role of
      FN in intravesical BCG immunotherapy.

PMID- 7719288
TI  - Renal high-dose extracorporeal shock wave treatment (ESWT) raises blood pressure
      in borderline hypertensive rats.

PMID- 7719289
TI  - Role of contralateral kidney in the maintenance of two-kidney, one-clip
      renovascular hypertension.

PMID- 7719290
TI  - Kidney preservation in situ and conservative treatment of renal cell carcinoma:
      application of HTK solution (CUSTODIOL).

PMID- 7719291
TI  - p53 mutant gene expression in paraffin embedded and fresh frozen tissue of
      different urogenital tumors.

PMID- 7719292
TI  - Sodium absorption in the sigma-rectum pouch, augmented rectal bladder and
      ureterosigmoidostomy.

PMID- 7719293
TI  - Urinary diversion and changes in bone architecture: long-term results in an
      animal model.

PMID- 7719294
TI  - Radiology and urodynamics of spontaneous reflux, surgically-induced reflux and
      non-refluxing renal units in pigs.

PMID- 7719295
TI  - Further optimization of stimulation parameters in sacral electrostimulation for
      bladder emptying: first experiences with a new implantable bladder stimulator.

PMID- 7719296
TI  - Reduction of detrusor-sphincter dyssynergia during ventral sacral root
      stimulation: anatomical and electrophysiological experiments.

PMID- 7719297
TI  - Electrical neurostimulation in the male Wistar rat: proximal stimulation of the
      nervi pelvicus sive pudendus.

PMID- 7719298
TI  - The influence of S3-sacral nerve blockade on the sensation of bladder mucosa.

PMID- 7719299
TI  - Mechanical and electrophysiological effects of cromakalim on the human urinary
      bladder.

PMID- 7719300
TI  - Computerized nuclear morphometry: prognostic value for carcinoma of the prostate
      and renal cell carcinoma.

PMID- 7719301
TI  - Free versus pedicled fascial flaps--a chronic animal study.

PMID- 7719302
TI  - Radiotelemetric manometry of the urinary bladder.

PMID- 7719303
TI  - Evaluation of the smooth muscle EMG with MYDAS, a numerical signal analysis
      program package.

PMID- 7719304
TI  - Muscular cavernous single cell analysis (MCSCA) in patients with venoocclusive
      dysfunction (VOD).

PMID- 7719305
TI  - The ejaculation into the posterior urethra.

PMID- 7719306
TI  - Impacts of the shock wave pattern of electrohydraulic lithotripsy in the ureter.

PMID- 7719307
TI  - Comparison of different lithotripters according to "disintegrative efficacy" (DE)
      and "disintegrative range" (DR) using an in vitro stone model.

PMID- 7719308
TI  - Preoperative determination of urinary stones with methyldiphosphonates.

PMID- 7719309
TI  - Formation of spherulites of calcium phosphate and crystallization of calcium
      oxalate in gel in a new experimental model of urinary stone formation.

PMID- 7719310
TI  - Microbial degradation of dietary oxalate in the human gut and urinary oxalate
      concentrations in patients with calcium oxalate urolithiasis and control persons.

PMID- 7719311
TI  - New drugs for renal colic therapy--in-vitro and animal experiments.

PMID- 7719312
TI  - The Holmium-YAG-laser as a new cutting instrument in the ureter.

PMID- 7719313
TI  - Epithelial interaction in carcinogenesis complicating ureterosigmoidostomy.

PMID- 7719314
TI  - Separation of urologic tumor cells from red blood cells by the use of a cell
      saver and membrane filters.

PMID- 7719315
TI  - Surface specification of endoscope shafts.

PMID- 7719316
TI  - Fibrin-glue vasovasostomy as an alternative to the conventional two-layer suture
      technique?

PMID- 7719317
TI  - Feasibility of engaging gene therapeutic principles in intensifying classical
      chemotherapy.

PMID- 7719318
TI  - Establishment and characterization of human renal cancer cell lines and
      autologous normal kidney short term cultures.

PMID- 7719319
TI  - Beta-1 integrins in renal cell carcinoma--an immunohistochemical study.

PMID- 7719320
TI  - Intercellular adhesion molecule 1 (ICAM-1) and insulinlike growth factor 1 (IGF
      1) in patients with renal cell carcinoma.

PMID- 7719321
TI  - HLA class I expression in primary and metastatic renal cell carcinoma.

PMID- 7719322
TI  - Tumor heterogeneity as prognostic factor in patients with low-stage (T1-3N0M0)
      renal-cell carcinoma.

PMID- 7719323
TI  - Monoclonal antibody 138H11 in immunoscintigraphy of human kidney tumors--in vitro
      results.

PMID- 7719324
TI  - Isolation of isotype variants from hybridomas producing monoclonal antibodies to
      urothelial cancer associated antigens.

PMID- 7719325
TI  - Gene expression in superficial bladder cancer in a tumor-model-system (RBT).

PMID- 7719326
TI  - Motility- and adhesion factors in bladder carcinoma.

PMID- 7719327
TI  - Photodynamic diagnosis following topical application of delta-aminolevulinic acid
      in a rat bladder tumor model.

PMID- 7719328
TI  - Laser-induced fluorescence measurement of the photosensitizer phthalocyanine in
      two tumor models in vivo.

PMID- 7719329
TI  - Craniofacial syndromes: no such thing as a single gene disease.

PMID- 7719330
TI  - Resolving DNA mutations.

PMID- 7719331
TI  - Telomerase: immortality enzyme or oncogene?

PMID- 7719332
TI  - Can we avoid AVED?

PMID- 7719333
TI  - FGFR2 mutations in Pfeiffer syndrome.

PMID- 7719334
TI  - Loss of imprinting in choriocarcinoma.

PMID- 7719335
TI  - An imprinted gene(s) for diabetes?

PMID- 7719336
TI  - SMA genes: deleted and duplicated.

PMID- 7719337
TI  - Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the
      peroxisome biogenesis disorders.
AB  - The peroxisome biogenesis disorders (PBDs) are lethal recessive diseases caused
      by defects in peroxisome assembly. We have isolated PXR1, a human homologue of
      the yeast P. pastoris PAS8 (peroxisome assembly) gene. PXR1, like PAS8, encodes a
      receptor for proteins with the type-1 peroxisomal targeting signal (PTS1).
      Mutations in PXR1 define complementation group 2 of PBDs and expression of PXR1
      rescues the PTS1 import defect of fibroblasts from these patients. Based on the
      observation that PXR1 exists both in the cytosol and in association with
      peroxisomes, we propose that PXR1 protein recognizes PTS1-containing proteins in
      the cytosol and directs them to the peroxisome.

PMID- 7719338
TI  - Gene therapy in a xenograft model of cystic fibrosis lung corrects chloride
      transport more effectively than the sodium defect.
AB  - We have developed a model of gene therapy for cystic fibrosis (CF) lung disease,
      based on growth of human CF bronchial xenografts in nu/nu mice. We now report an
      evaluation of the primary abnormalities in CF lung epithelia--defective Cl
      secretion and Na hyperabsorption--in xenografts following adenovirus-mediated
      gene transfer. In vivo infection of CF xenografts with a cystic fibrosis
      transmembrane regulator (CFTR) recombinant adenovirus, at a multiplicity of
      infection equal to 100, was sufficient to reconstitute near normal levels of cAMP
      stimulated Cl transport, despite transducing only 5% of cells in the
      pseudostratified epithelium. Correction in sodium hyperabsorption was partial and
      variable. These experiments define aspects of adenovirus-mediated gene therapy
      relevant to CF protocols based on intrapulmonary genetic reconstitution.

PMID- 7719339
TI  - The detection of subtelomeric chromosomal rearrangements in idiopathic mental
      retardation.
AB  - A major challenge for human genetics is to identify new causes of mental
      retardation, which, although present in about 3% of individuals, is unexplained
      in more than half of all cases. We have developed a strategy to screen for the
      abnormal inheritance of subtelomeric DNA polymorphisms in individuals with mental
      retardation and have detected three abnormalities in 99 patients with normal
      routine karyotypes. Pulsed-field gel electrophoresis and reverse chromosome
      painting showed that one case arose from an interstitial or terminal deletion and
      two from the de novo inheritance of derivative translocation chromosomes. At
      least 6% of unexplained mental retardation is accounted for by these relatively
      small chromosomal abnormalities, which will be an important resource in the
      characterization of the genetic basis of neurodevelopment.

PMID- 7719340
TI  - Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha
      tocopherol transfer protein.
AB  - Ataxia with isolated vitamin E deficiency (AVED) is an autosomal recessive
      neurodegenerative disease which maps to chromosome 8q13. AVED patients have an
      impaired ability to incorporate alpha-tocopherol into lipoproteins secreted by
      the liver, a function putatively attributable to the alpha-tocopherol transfer
      protein (alpha-TTP). Here we report the identification of three frame-shift
      mutations in the alpha TTP gene. A 744delA mutation accounts for 68% of the
      mutant alleles in the 17 families analysed and appears to have spread in North
      Africa and Italy. This mutation correlates with a severe phenotype but alters
      only the C-terminal tenth of the protein. Two other mutations were found in
      single families. The finding of alpha TTP gene mutations in AVED patients
      substantiates the therapeutic role of vitamin E as a protective agent against
      neurological damage in this disease.

PMID- 7719341
TI  - An autosomal locus predisposing to deletions of mitochondrial DNA.
AB  - The molecular mechanisms by which the nuclear genome regulates the biosynthesis
      of mitochondrial DNA (mtDNA) are only beginning to be unravelled. A naturally
      occurring in vivo model for a defect in this cross-talk of two physically
      separate genomes is a human disease, an autosomal dominant progressive external
      ophthalmoplegia, in which multiple deletions of mtDNA accumulate in the patients'
      tissues. The assignment of this disease locus to 10q 23.3-24.3 is the first
      direct evidence for involvement of both nuclear and mitochondrial genomes in a
      single disorder.

PMID- 7719342
TI  - Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their
      recent descent from a small founder population.
AB  - We have examined data on six closely linked microsatellite loci on chromosome
      9q34 from 59 Ashkenazi Jewish families with idiopathic torsion dystonia (ITD).
      Our data show that the vast majority (> 90%) of early-onset ITD cases in the
      Ashkenazi population are due to a single founder mutation, which we estimate
      first appeared approximately 350 years ago. We also show that carriers
      preferentially originate from the northern part of the historic Jewish Pale of
      settlement (Lithuania and Byelorussia). The recent origin of this dominant
      mutation and its current high frequency (between 1/6,000 and 1/2,000) suggest
      that the Ashkenazi population descends from a limited group of founders, and
      emphasize the importance of genetic drift in determining disease allele
      frequencies in this population.

PMID- 7719343
TI  - Male pseudohermaphroditism due to a homozygous missense mutation of the
      luteinizing hormone receptor gene.
AB  - Leydig cell hypoplasia is a rare autosomal recessive condition that interferes
      with normal development of male external genitalia in 46,XY individuals. We have
      studied two Leydig cell hypoplasia patients (siblings born to consanguineous
      parents), and found them to be homozygous for a missense mutation (Ala593Pro) in
      the sixth transmembrane domain of the luteinizing hormone (LH) receptor gene. In
      vitro expression studies showed that this mutated receptor binds human
      choriogonadotropin with a normal KD, but the ligand binding does not result in
      increased production of cAMP. We conclude that a homozygous LH receptor gene
      mutation underlies the syndrome of autosomal recessive congenital Leydig cell
      hypoplasia in this family. These results have implications for the understanding
      of the development of the male genitalia.

PMID- 7719344
TI  - Apert syndrome results from localized mutations of FGFR2 and is allelic with
      Crouzon syndrome.
AB  - Apert syndrome is a distinctive human malformation comprising craniosynostosis
      and severe syndactyly of the hands and feet. We have identified specific missense
      substitutions involving adjacent amino acids (Ser252Trp and Pro253Arg) in the
      linker between the second and third extracellular immunoglobulin (Ig) domains of
      fibroblast growth factor receptor 2 (FGFR2) in all 40 unrelated cases of Apert
      syndrome studied. Crouzon syndrome, characterized by craniosynostosis but normal
      limbs, was previously shown to result from allelic mutations of the third Ig
      domain of FGFR2. The contrasting effects of these mutations provide a genetic
      resource for dissecting the complex effects of signal transduction through FGFRs
      in cranial and limb morphogenesis.

PMID- 7719345
TI  - Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome
      phenotypes.
AB  - Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have been
      identified in Crouzon syndrome, an autosomal dominant condition causing premature
      fusion of the cranial sutures (craniosynostosis). A mutation in FGFR1 has been
      established in several families with Pfeiffer syndrome, where craniosynostosis is
      associated with specific digital abnormalities. We now report point mutations in
      FGFR2 in seven sporadic Pfeiffer syndrome patients. Six of the seven Pfeiffer
      syndrome patients share two missense mutations, which have also been reported in
      Crouzon syndrome. The Crouzon and Pfeiffer phenotypes usually breed true within
      families and the finding of identical mutations in unrelated individuals giving
      different phenotypes is a highly unexpected observation.

PMID- 7719346
TI  - Detection of mutations by cleavage of DNA heteroduplexes with bacteriophage
      resolvases.
AB  - We have explored the application of the bacteriophage resolvases T4 endonuclease
      VII and T7 endonuclease I for detecting mutations in genomic DNA. Heteroduplex
      DNA fragments prepared by amplification from DNA containing known mutations were
      cleaved by one or both enzymes at nucleotide mismatches created by 3 of 3 short
      deletions and 13 of 14 point mutations in fragments as large as 940 basepairs.
      Heteroduplexes representing all four classes of possible single nucleotide
      mismatches were cleaved, and the sizes of the cleavage products generated
      correlated with the location of the mutation. We conclude that bacteriophage
      resolvases may be useful reagents for the rapid screening of DNA for mutations.

PMID- 7719347
TI  - The human dystrophin gene requires 16 hours to be transcribed and is
      cotranscriptionally spliced.
AB  - The largest known gene is the human dystrophin gene, which has 79 exons spanning
      at least 2,300 kilobases (kb). Transcript accumulation was monitored from four
      regions of the gene following induction of expression in muscle cell cultures.
      Quantitative reverse transcription-polymerase chain reaction (RT-PCR) results
      indicate that approximately 12 h are required for transcription of 1,770 kb (at
      an average elongation rate of 2.4 kb min-1), extrapolating to a transcription
      time of 16 h for the complete gene. Accumulation profiles for spliced and total
      transcript demonstrated that transcripts are spliced at the 5' end before
      transcription is complete providing strong evidence for cotranscriptional
      splicing. The rate of transcript accumulation was reduced at the 3' end of the
      gene relative to the 5' end, perhaps due to premature termination of
      transcription complexes.

PMID- 7719348
TI  - Stability of an expanded trinucleotide repeat in the androgen receptor gene in
      transgenic mice.
AB  - The expansion of trinucleotide repeat sequences underlies a number of hereditary
      neurological disorders. To study the stability of a trinucleotide repeat and to
      develop an animal model of one of these disorders, spinal and bulbar muscular
      atrophy (SBMA), we have generated transgenic mice carrying either the normal or
      expanded repeat human androgen receptor (AR) gene. Unlike the disease allele in
      humans, the AR cDNA containing the expanded repeat in transgenic mice showed no
      change in repeat length with transmission. Expression of the SBMA AR was found in
      transgenic mice, but at a lower level than normal endogenous expression. The lack
      of a physiological pattern of expression may explain why no phenotypic effects of
      the transgene were observed.

PMID- 7719349
TI  - Rescue of neurophysiological phenotype seen in PrP null mice by transgene
      encoding human prion protein.
AB  - The prion protein (PrP) is central to the aetiology of the prion diseases,
      transmissible neurodegenerative conditions of humans and animals. PrP null mice
      show abnormalities of synaptic neurophysiology, in particular weakened GABAA
      receptor-mediated fast inhibition and impaired long-term potentiation in the
      hippocampus. Here we demonstrate that this PrP null phenotype is rescued in mice
      with a high copy number of a transgene encoding human PrP but not in low copy
      number mice, confirming the specificity of the phenotype for loss of function of
      PrP. The ability of human PrP to compensate for loss of murine PrP will allow
      direct study of the functional consequences of the 18 human PrP mutations, which
      cause the inherited prion diseases; this phenotype can now form the basis of the
      first functional assay for PrP.

PMID- 7719351
TI  - Questions of intelligence.

PMID- 7719352
TI  - Jewish diseases and origins.

PMID- 7719350
TI  - Mouse model of X-linked chronic granulomatous disease, an inherited defect in
      phagocyte superoxide production.
AB  - Chronic granulomatous disease (CGD) is a recessive disorder characterized by a
      defective phagocyte respiratory burst oxidase, life-threatening pyogenic
      infections and inflammatory granulomas. Gene targeting was used to generate mice
      with a null allele of the gene involved in X-linked CGD, which encodes the 91 kD
      subunit of the oxidase cytochrome b. Affected hemizygous male mice lacked
      phagocyte superoxide production, manifested an increased susceptibility to
      infection with Staphylococcus aureus and Aspergillus fumigatus and had an altered
      inflammatory response in thioglycollate peritonitis. This animal model should aid
      in developing new treatments for CGD and in evaluating the role of phagocyte
      derived oxidants in inflammation.

PMID- 7719353
TI  - [Lymphoma with bladder involvement and renal transplantation].
AB  - Based on the case of a renal transplant recipient who developed a monoclonal B
      cell lymphoma with plasma cell differentiation, arising in the bladder, the
      authors discuss the responsibility of intensive immunosuppressant protocols in
      the development of post-transplantation lymphoproliferative syndromes. The
      Epstein-Barr virus favours the development of these lymphomas. The bladder is a
      rare site. Diagnosis was based on endoscopic resection with immunohistochemical
      analysis. The prognosis depends on the stage at the time of diagnosis. At an
      early stage, resection of the tumour combined with reduction of immunosuppressant
      therapy may be sufficient, but more aggressive treatment is required for more
      advanced stages. Anti-B lymphocyte monoclonal antibodies (CD21, CD24) give good
      results, especially in polyclonal forms and Epstein-Barr virus primo-infections.
      Anti-CD38 monoclonal antibodies are currently being investigated and appear to be
      very promising. Conventional radiotherapy and chemotherapy are disappointing.

PMID- 7719354
TI  - [Post-traumatic hematoma of the adrenal gland. Apropos of a case and review of
      the literature].
AB  - The authors report a case of delayed diagnosis of traumatic haematoma of the
      right adrenal gland. Chronic unilateral haematomas are rare and their
      preoperative diagnosis is often difficult because of the long interval since
      trauma, which may be completely forgotten. This raises the problem of an adrenal
      mass whose origin is often only detected on histology of the operative specimen.

PMID- 7719355
TI  - [Interstitial cystitis].

PMID- 7719356
TI  - [Interstitial cystitis].
AB  - Interstitial cystitis, first described one hundred years ago, is difficult to
      classify in urological pathology. It essentially affects middle-aged women. Two
      main theories are currently proposed to explain its pathogenesis: the permeable
      epithelium theory and the mast cell theory. However, other factors are also
      involved: vascular, neurological, infectious and immune. This disease has a
      chronic course with no transformation of the nonulcerative form into the
      ulcerative form. There are no specific histological criteria, even the presence
      of mast cells in the bladder wall. However, histology is able to exclude other
      bladder disease, principally carcinoma in situ. The diagnosis is therefore based
      on clinical examination and endoscopy, after excluding other diseases. The
      essential complementary investigations are cystoscopy and cystomanometry which
      must be performed according to rigorous protocols. Conservative treatment is
      based on vesical hydrodistension, bladder retraining, bladder instillations
      (DMSO) and systemic treatments (sodium pentosanpolysulfate). Surgery is required
      in 1 to 5% of cases due to failure of medical treatment and the severity of the
      symptoms. Electrical or laser coagulation of the ulcers is effective. Partial
      cystectomy with cystoplasty is reserved for forms sparing the trigone, while
      cystourethrectomy and urinary diversion may be indicated in other more advanced
      and refractory cases.

PMID- 7719357
TI  - [Cancer of the prostate. 2. Physiology and cellular development].
AB  - Prostatic cancer is the second most frequent cancer in men in industrialised
      countries. The histological analysis of its initial development demonstrates the
      existence of precancerous lesions, PIN. The initial presence of several different
      cell populations accounts for the development of contingents of hormone-sensitive
      and hormone-resistant cells. The presence of numerous neuroendocrine cells
      appears to be a factor of poor prognosis. Hormones are intimately involved in the
      development of prostatic cancer and are an integral part of its treatment.
      Progress in molecular biology has furthered out knowledge of this disease. In
      particular, growth factors such as EGF and FGF are particularly involved and are
      starting to have a clinical application. The oncogene and anti-oncogene system is
      currently being explored (particularly p53 abd BCL 2). They are the basis for
      carcinogenesis and analysis of these factors will allow a better approach to the
      mechanisms of tumour induction and development.

PMID- 7719358
TI  - [Changes in urethral pressure after intravenous injection of moxisylyte
      hydrochloride in urethral instability in women. Preliminary results].
AB  - OBJECTIVE: To study the action of an alpha blocker, Moxisylyte hydrochloride,
      during an intravenous test on the course of urethral pressure in women with
      urethral instability associated with urethral hypertonia. METHODS: The population
      consisted of 20 women with a mean age of 38 years, presenting with a clinical
      disorder of micturition (urinary incontinence: 15 cases, urgency: 17 cases,
      frequency, 17 cases) present for an average of 4 years and associated with
      resting urethral pressure variations ranging from 22 to 88 cm H2O (mean: 44.8 cm
      H2O) and static urethral pressures ranging 72 to 150 cm H2O (mean: 102.5 cm H2O).
      An urodynamic assessment was performed before and after intravenous injection of
      Moxisylyte hydrochloride at the dose of 0.5 mg/kg. RESULTS: Moxisylyte
      hydrochloride induced a significant reduction of urethral pressure variations,
      ranging from 8 to 42 cm H2O (mean: 21.9 cm H2O) and static urethral pressures,
      ranging from 47 to 102 cm H2O (mean: 68.8 cm H2O). Treatment was well tolerated
      in every case. CONCLUSION: These preliminary results need to be completed by a
      randomized placebo-controlled study to confirm a statistically significant effect
      of Moxisylyte hydrochloride on urethral pressure stability in women presenting
      with urethral instability.

PMID- 7719359
TI  - [Analysis of the failure of endoscopic treatment of vesico-renal reflux in
      children using injections of teflon and collagen and the preliminary results of
      injections of Macroplastic].
AB  - This study of 785 cases of vesicorenal reflux in 494 children treated
      endoscopically over a 7-year period was designed to evaluate the results obtained
      with three products used successively: Teflon, collagen and Macroplastic.
      Following Teflon injection, despite a 90% short-term success rate, recurrent
      reflux was subsequently observed in 16.71% of the ureters reviewed. The failure
      rate was 52.63% after collagen injection and 11.77% after Macroplastic. After one
      or two injections, complete resolution of reflux was obtained in 48% of children
      treated with collagen, versus 85.72% with Teflon and 93.33% with Macroplastic. In
      one half of cases, failure was related to the quality of the product and its
      modifications after injection. The marked resorption of collagen accounts for the
      poor results despite the large doses injected. Apart from one case of partial
      resorption of Teflon paste, the failures with this product were due to
      lateralisation or secondary elimination of the product from the injection site
      due to its fluidity. Macroplastic, due to its higher viscosity and absence of
      retraction, currently provides the best results with doses of less than 0.20 ml
      in children.

PMID- 7719360
TI  - [A simple alternative method in the treatment of idiopathic hydrocele in adults:
      vaginal "fenestration"].
AB  - The author describes a new, simple technique for the treatment of idiopathic
      hydrocele according to a "fenestration" procedure designed to correct the
      imbalance of intravaginal hydrostatic exchanges. The operation consists of
      initially hemming separately the deep fibrous layer and the parietal leaflet of
      the tunica vaginalis to form the margins of the "window", which is then applied
      by its fibrous layer to the dartos, continuous with the subcutaneous connective
      tissue, a site of rich lymphatic drainage. In a series of 108 patients treated by
      this technique since September 1982, with a follow-up of 6 years, the anatomical
      and functional results were excellent in 98 cases (90.7%), moderate in 6 cases
      (5.5%) and poor in 4 cases (3.7%). Compared to classical techniques, the
      fenestrated opening of the tunica vaginalis with preservation of the tunica
      vaginalis and limited opening of the serosa, preserves the testicular support and
      the protective role of the serosa on the testis. Lastly, suture of the margins of
      the window to the dartos, by facilitating deep lymphatic drainage towards the
      superficial connective tissue, reconstitutes a physiological equilibrium in the
      constant exchanges of intravaginal serous fluids. Experience has demonstrated the
      anatomical and functional efficacy and reliability of this extremely simple
      procedure, which is essentially indicated in adult patients with idiopathic
      hydrocele and a healthy tunica vaginalis.

PMID- 7719362
TI  - [Trans-urethral bladder lithotripsy using the Lithoclast in children. Apropos of
      7 cases].
AB  - We report our experience with a new simple machine for endoscopic disintegration,
      the "Swiss Lithoclast". The principle of this lithotriptor is based on pneumatic
      shock waves induced by the central compressed air system of a hospital. This
      device was used to treat 7 children with bladder stone (5 boys, 2 girls); their
      age was between 7 and 9 years (average 8.2 years). Endoscopic fragmentation was
      successful in all patients and all were stone free before leaving the hospital.
      We have found the Swiss Lithoclast to be a safe, effective and inexpensive means
      of performing intra-corporeal lithotripsy for bladder stone in children.

PMID- 7719361
TI  - [Lumbar endoscopy: analysis and evaluation of 10 primary operations].
AB  - The authors report their experience of the first 10 patients operated by upper
      urinary tract lumboscopic surgery. Lumboscopy is performed in the lateral supine
      position and a simple technique for creation of retropneumoritoneum is described.
      In 4 patients, the planned nephrectomy could be performed because of poor
      anatomical conditions (peripyelitis and/or perinephritis). Lumboscopy allowed
      complete renal exploration, two nephrectomies, two resections of the roofs of
      compressive parapelvic cysts and one lumbar ureterolithotomy. The ease and
      rapidity of lumboscopic dissection makes it a valuable alternative to
      laparoscopy.

PMID- 7719363
TI  - [Primary percutaneous approach in staghorn kidney calculus].
AB  - 36 staghorn calculi were treated percutaneously under ultrasound guidance between
      1983 and 1992. Each stone had a renal pelvic element and at least two caliceal
      branches. The area of each stone was measured on the plain abdominal x-ray (mean:
      1,020 mm2) and the total length of the various caliceal branches was measured
      from the pelvic element (mean: 50.2 mm). These 36 procedures represented 8.2% of
      the 438 percutaneous nephrolithotomies performed over the same period. The stone
      was able to be entirely removed by nephrolithotomy in 12 patients. Of the 24
      residual stones after percutaneous nephrolithotomy, 16 were treated by
      extracorporeal shock-wave lithotripsy, which eliminated all stones in 12 of these
      patients. Eight of the remaining 12 patients were lost to follow-up and treatment
      was not completed, and 4 present a residual stone (11% of failures). These
      results are compared with those of other series and are comparable to those of
      surgery which gives a similar residual stone rate of 16% in the AFU 1982 report
      [6]. The primary percutaneous approach to staghorn calculi therefore represents
      an effective therapeutic modality, whose use and results must be weighed up with
      those of surgery.

PMID- 7719364
TI  - [Initial clinical experiences with the Storz Modulith SL 20 lithotripter: the
      results 3 months after a single session].
AB  - The objective of this study was to evaluate the performances of the Storz
      Modulith SL20 lithotriptor. Fifty patients with a total of 52 renal (31) or
      ureteric (21) stones were treated, in a single session, between June and October
      1993. The mean stone diameter was 7.9 mm. All patients were reviewed after 3
      months. The complete success rate, with radiological cure, was 65% at 3 months.
      The partial success rate, defined as fragmentation of the stone with persistence
      of residual fragments less than 3 mm in diameter, not requiring further
      treatment, was 12% at 3 months. The failure rate at 3 months was 23%. The
      commonest complication was renal colic in 12 patients (24%). Two patients
      developed an extrarenal haematoma. The Modulith SL20 possesses a good detection
      system: firing is well tolerated under minimal analgesia. Our success rates are
      slightly lower than those obtained by other teams using the same apparatus.

PMID- 7719365
TI  - [A para-pelvic cyst compressing the pyelo-caliceal region in an asymptomatic 19
      year-old man].
AB  - Parapelvic cysts in children, adolescents and young adults are rare. We report
      the case of an asymptomatic nineteen year old male with a large parapelvic cyst
      causing obstruction and distortion of the pelvocalyceal system.

PMID- 7719367
TI  - [Kidney transplantectomy: a multicenter study of the Committee of Transplantation
      of the French Urology Association].
AB  - OBJECTIVES: Multicentre study of the Transplantation Committee of the Association
      Francaise d'Urologie (French Urology Association) concerning the attitudes of
      various French transplantation centres in relation to renal transplantectomy.
      METHODS: Nine centres participated in this study: Bordeaux, Brest, Grenoble,
      Marseille, Nantes, Paris-Necker, Paris-La Pitie, Strasbourg and Toulouse. The
      survey was performed by means of 2 types of forms: study of transplantectomies
      performed between 1982 and 1992, specific study of transplantectomies performed
      in 1992. RESULTS: From 1982 to 1992, 731 transplantectomies were performed in
      these centres, i.e. 15% of all renal transplantations. Rejection represented 80%
      of the indications and vascular complications represented 15%. The technique used
      before the 6th week was complete removal of the transplant. After this period,
      the transplant was removed via a subcapsular approach. The postoperative
      mortality was 0.7% and the morbidity was 26%. In 1992, 91 transplantectomies were
      performed in these different centres. Forty-two per cent of the transplants
      presented with local signs and 38% with general signs. A subcapsular
      transplantectomy was performed in 84% of cases, for rejection in every case. The
      morbidity was 16%. Complete removal of the transplant was performed in 16% of
      cases, essentially for infectious complications. The morbidity was 7%.
      CONCLUSION: The renal transplantectomy technique must be adapted to the interval
      after transplantation: before the 6th week, the transplant must be completely
      removed; after this period, subcapsular transplantectomy must be performed. This
      operation therefore no longer carries the mortality and morbidity attributed to
      it.

PMID- 7719366
TI  - [Extracorporeal shockwave lithotripsy and hemophilia: apropos of a case].
AB  - We report pelvis calculi fragmentation through the use of extracorporeal shock
      wave lithotripsy in a patient with mild hemophilia B. The EDAP LT 01 lithotriptor
      was used without incident. We review other reported cases in the literature.

PMID- 7719368
TI  - [The treatment of genito-urinary prolapse with promonto-fixation using a
      prosthetic material combined with complete hysterectomy: complications and
      results apropos of a series of 55 cases].
AB  - From May 1986 to May 1992, 55 patients with genitourinary prolapse were treated
      by total hysterectomy, sacral fixation using a prosthetic band and
      colposuspension. The mean age was 55.5 years (range: 38-78 years). Ten patients
      (18.8%) developed early postoperative complications: 2 wall haematomas, one
      surgical revision for haemorrhage, one case of haematemesis secondary to a
      duodenal ulcer, one intestinal obstruction due to dehiscence of the
      peritonealisation, two cases of acute urinary retention, one case of complete
      urinary incontinence, one septic shock and one wall abscess. Three patients
      (5.4%) developed late postoperative complications: intestinal obstruction
      secondary to a mesenteric band, one incisional hernia, and one case of pelvic
      pain. The mean length of hospital stay was 8.9 days (range: 7-25 days) and the
      mean follow-up was 36 months (range: 6-72 months). The anatomical result was
      excellent (complete correction of the prolapse and absence of recurrence) in
      96.4% of cases. In terms of the functional results, 3 patients (5.4%) remained
      dysuric and 5 (9.1%) have persistent stress incontinence, either moderate (3
      cases) or disabling (2 cases). Marked sphincter insufficiency was demonstrated on
      the urethral pressure profile in these last two cases. The combination of total
      hysterectomy with vaginal opening and sacral fixation using a prosthetic band
      prevents the risk of subsequent disease of the remaining cervix and does not
      appear to increase the risk of infection or the postoperative morbidity. Without
      advocating systematic hysterectomy in the sacral fixation technique, we
      nevertheless believe that it is preferable to perform total hysterectomy rather
      than supraisthemic hysterectomy when this procedure is indicated.

PMID- 7719369
TI  - [T1 G3 bladder tumors: the respective role of BCG and cystectomy].
AB  - Forty eight patients with T1 G3 bladder cancer were treated between 1975 and
      1991. An associated carcinoma in situ in one third of cases. Twenty six patients
      received intravesical BCG instillations (an average of 2.5 courses of 6
      instillations) with no local recurrence or metastases in 50% of cases (mean
      follow-up: 54 months). Thirteen patients developed recurrence after a mean
      disease-free interval of 8 months (range: 3 to 18 months: 7 with disease
      progression, 5 at an identical stage and 1 Ta. Six cystectomies were performed in
      this group over the following two years: 3 patients were cured with a mean follow
      up of 33 months, 2 died from their cancer, 1 patient is alive with an urethral
      redux. In view of age and/or clinical context, 7 patients were treated by
      repeated resections and other local treatments: 3 relapsed without progression, 2
      died from their cancer and 2 have been lost to follow-up. Twenty one cystectomies
      were performed as first-line treatment: 20 patients are recurrence-free with a
      mean follow-up of 47 months and one patient died from cancer within 6 months. T1
      G3 bladder cancer should be considered to be a lesion with a poor prognosis,
      requiring active treatment. First-line BCG therapy is effective in 50% of cases,
      but cystectomy is required in the absence of response to BCG.

PMID- 7719370
TI  - [A continent urostomy. An ileal pouch and the Benchekroun valve].
AB  - The authors reported their experience using detubularized ileal pouch and
      Benchekroun hydraulic valve. They obtain continence in all patients, and
      antireflux in only 12 of them. 30 patients were operated according to this
      technique from January 1986 to December 1992. The main indication was represented
      by vesical tumors, treated by cystoprostatectomy. 90% of the patients operated
      this way are continent, when 10% were reoperated to achieve continence. They
      point out in the follow-up the steady state of renal function, and
      radiologically, the improvement or at least the stabilization of pyelo-ureteral
      dilatation, and the absence of ureteral reflux, especially when antireflux system
      was performed using Benchekroun hydraulic valve.

PMID- 7719371
TI  - [Perinephritic cellulitis. Apropos of 75 cases].
AB  - In spite of the contribution of the new techniques of radiology and the use of
      new antibiotics, the diagnosis of perinephric abscess remains difficult and late
      and is at the origin of high morbidity and mortality. 75 cases of perinephric
      abscess collected during 15 years are reviewed. We studied the etiopathogenic,
      diagnostic, bacteriologic and therapeutic characteristics of this affection.
      Urinary signs are found in 26.7% of patients, diabetes in 17% and extra urinary
      origin is found in 11% of patients. Diagnostic delay is over one month in 75% of
      patients. Ultrasonography is carried out in 55 patients showing evocative images
      of perinephric abscess in 96% of cases. Computed tomography seems more performant
      than ultrasonography. Gram negative bacillus and staphylococcus are the germs
      which are the most frequently found. Surgical drainage associated to
      antibiotherapy is realized in all patients with collected perinephric abscess (73
      cases). Evolution is often favourable in spite of the expanse of the abscedation.
      Literature data about pathogenesis, bacteriology, diagnosis and treatment of this
      affection are discussed.

PMID- 7719372
TI  - [Tumors of the Bellini collecting tubules. Apropos of a case].
AB  - Based on a personal case and a review of the literature, the authors describe the
      particular features of renal tumours arising from the papillary ducts of Bellini.
      The most remarkable feature of this rare lesion, which has a very poor prognosis,
      is that it arises in the medullary zone of the kidney. The histological diagnosis
      is often difficult to confirm and immunohistochemical techniques are essential.
      The possible role of adjuvant chemotherapy following nephrectomy and the type of
      regimens used are discussed.

PMID- 7719373
TI  - [Pseudo-tumoral cystitis due to Toxoplasma in an patient with AIDS].
AB  - The authors report a case of cystitis due to Toxoplasma Gondii infection in a
      patient suffering from AIDS. Initial symptoms consisted of dysuria, extreme
      frequency and urgent micturition responsible for pseudo urinary incontinence.
      Urine culture was sterile. Pelvic computed tomography and pelvic MRI demonstrated
      thickening of the bladder wall and seminal vesicles. Cystoscopy confirmed the
      presence of an intravesical proliferation with a pseudoneoplastic appearance. The
      diagnosis of Toxoplasma cystitis was confirmed by the discovery of Toxoplasma
      cysts on histological examination of bladder biopsies. Toxoplasma cystitis is a
      rare cause of pseudoneoplastic bullous cystitis in HIV-seropositive patients.

PMID- 7719374
TI  - [Pure primary carcinoid tumor of the testis. Apropos of a case].
AB  - The authors report a case of pure primary carcinoid tumour of the testis. This is
      a rare tumour which can only be diagnosed by histological examination of the
      resection specimen. They may be primary or metastatic, with radically different
      prognoses. The diagnosis of such lesions requires the search for the primary
      carcinoid tumour.

PMID- 7719375
TI  - The war on cancer: new battle plan needed.

PMID- 7719376
TI  - Irreversible, severe congestive cardiomyopathy occurring in association with
      interferon alpha therapy.
AB  - Interferon alpha is a biologic agent with demonstrated anti-tumor activity in a
      variety of hematologic and solid malignancies. Many patients treated with
      interferon experience acute toxicity manifested as a flu-like syndrome of fever,
      chills, myalgias, and malaise. However, fatigue, anorexia, bone marrow
      suppression, nausea, vomiting, dizziness, and confusion may also occur.
      Cardiotoxicity is a rare complication of interferon therapy that most frequently
      presents as transient episodes of hypotension and tachycardia, with few
      significant life-threatening cardiovascular effects reported. A small number of
      cases of suspected interferon-induced cardiomyopathy, all of which improved after
      discontinuing interferon, have recently been documented. We report a patient with
      multiple myeloma who developed severe congestive cardiomyopathy while receiving
      interferon alpha that did not reverse subsequent to discontinuation of interferon
      therapy. Although the patient had previously received doxorubicin, the presence
      on endomyocardial biopsy of a prominent intracellular lipid accumulation within
      myocytes and only grade 2 anthracycline cardiotoxicity suggested that other or
      additional factor(s) contributed to the severity of this patient's
      cardiomyopathy. Etiologies of cardiac dysfunction other than interferon and
      doxorubicin were excluded. While a direct cause-effect relationship between
      interferon alpha and irreversible congestive cardiomyopathy cannot be firmly
      established in this case report, patients who either concurrently or sequentially
      receive interferon and anthracyclines should be carefully monitored for evidence
      of cardiac toxicity.

PMID- 7719377
TI  - Treatment of advanced colorectal carcinoma with 5-fluorouracil, leucovorin and
      Roferon-A: a Southwest Oncology Study Group Study.
AB  - Based upon prior data suggesting that alpha-interferon possesses chemomodulatory
      activity, a pilot study was conducted in which patients with advanced colorectal
      carcinoma were treated with 5-fluorouracil (5-FU), leucovorin (LV) and Roferon-A.
      Treatment consisted of LV 20 mg/m2 i.v. push followed by 5-FU, 425 mg/m2 i.v.
      push daily for 5 days every 4 weeks for 2 cycles, then every 5 weeks; Roferon-A 9
      million units subcutaneously was given three times weekly every week. Forty-six
      eligible patients with bidimensionally measurable disease who had received no
      prior chemotherapy for advanced disease were treated with this regimen. The most
      frequent toxicity was leukopenia with 80% of patients experiencing some degree of
      leukopenia and the most severe toxicity was granulocytopenia with 46% of patients
      experiencing granulocyte counts < 1,000/mm3. Among the 46 eligible patients, the
      objective response rate was 13% (95% confidence interval, 5-26%). Thirty-five of
      the 46 patients have died with a median survival of 17 months. This regimen has
      significant toxicity and insufficient activity against advanced colorectal
      carcinoma to warrant further trials.

PMID- 7719378
TI  - In vivo time and dose dependency of interleukin-6 secretion in response to low
      dose subcutaneous recombinant interleukin-2.
AB  - Serum concentrations of Interleukin-6 (IL-6) were determined in renal cell
      carcinoma patients treated with low-dose subcutaneous human recombinant
      interleukin-2 (rIL-2). In all patients, administration of rIL-2 resulted in a
      significant increase in IL-6 serum levels to peak values within 4 to 6 hours as
      measured by enzyme-linked immunosorbent assays (ELISA). Repetitive administration
      of rIL-2 induced significantly lower IL-6 serum peaks when compared to the
      initial administration of rIL-2. Cumulative IL-6 release, as expressed by the
      area under the concentration curve (AUC), appeared to be independent of rIL-2
      dose distribution (10 million IU rIL-2/m2 versus 20 million IU rIL-2/m2), and IL
      6 serum peaks showed no direct dose dependency. Prior rIL-2 immunotherapy had no
      measurable effect on rIL-2 induced IL-6 release, while steroids resulted in a
      significant suppression of secondary IL-6 did not correlate with response to rIL
      2 therapy or survival of rIL-2 treated renal cell carcinoma patients.

PMID- 7719379
TI  - Immunotherapy with low-dose interleukin-2 and anti-transforming growth factor
      beta antibody in a murine tumor model.
AB  - The purpose of the present study was to evaluate the therapeutic efficacy of low
      dose interleukin-2 (IL-2) alone or together with antibody against transforming
      growth factor-beta (TGF-beta) in a Herpes simplex virus Type 2-transformed (H238)
      fibrosarcoma model. BALB/c mice were inoculated subcutaneously (s.c.) with 5 x
      10(5) H238 tumor cells in one or both hind thighs and treated with IL-2, anti-TGF
      beta, or a combination of both agents. Nontreated tumor-bearing and normal
      animals served as controls. In the appropriate treatment groups, each mouse was
      given a total of 10(5) international units (i.u.) of IL-2 s.c. at one tumor
      implantation site and/or 1 microgram of anti-TGF-beta intraperitoneally (i.p.)
      over a period of 5 days beginning on the day of tumor cell implantation. No
      toxicity was noted during treatment. The slowest tumor growth was observed in
      mice with single tumors when treated with IL-2 or anti-TGF-beta alone, whereas
      combination treatment resulted in growth similar to that of untreated controls.
      However, in animals with two tumors, the tumor injected with IL-2 grew more
      rapidly than the untreated one. Spleen cell responsiveness to mitogenic
      stimulation was generally depressed in tumor-bearing mice compared to normal
      controls, but some differences were noted with treatment. In contrast, tumor
      presence induced striking splenomegaly and enhanced the chemiluminescent
      oxidative burst of phagocytic cells in the spleen. In the groups with a single
      tumor, plasma TGF-beta levels were similar to those of nontumor-bearing controls,
      however the concentrations were decreased in the animals with two tumors. These
      results show that IL-2 or anti-TGF-beta can slow progression of H238 tumors under
      certain conditions. However, combination of the two modalities proved to be of no
      benefit.

PMID- 7719380
TI  - Induction of serum tumor necrosis factor-alpha and interleukin-6 activity by
      liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) in
      normal cats.
AB  - Tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) are products of
      activated monocytes/macrophages with anti-tumor activity. Liposome-encapsulated
      muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) is a potent
      monocyte/macrophage activator. Sera from cats after intravenous L-MTP-PE
      administration showed TNF alpha activity using a WEHI-164 cell cytotoxicity assay
      and IL-6 activity using an IL-6 dependent mouse 7TD1 hybridoma cell proliferation
      assay. Serum TNF alpha activity peaked at 2 hours after L-MTP-PE administration.
      Significant differences from lipid-equivalent controls were observed at 2 and 3
      hours (P < 0.05). Neutralization of serum TNF alpha activity was accomplished
      with serial dilutions of rhTNF alpha monoclonal antibody. Serum IL-6 activity
      peaked at 3 hours after L-MTP-PE administration. Significant differences from
      lipid-equivalent controls were observed at 2, 3, and 4 hours (P < 0.05).
      Neutralization of serum IL-6 activity was not achieved with goat anti-rhIL-6
      polyclonal antibody. Intravenous L-MTP-PE, but not lipid-equivalent, induces
      serum TNF alpha and IL-6 activity in normal cats.

PMID- 7719382
TI  - Enhancement of anti-cancer activity of cisdiaminedichloroplatinum by the protein
      bound polysaccharide of Coriolus versicolor QUEL (PS-K) in vitro.
AB  - The protein-bound polysaccharide of Coriolus versicolor QUEL (PS_K) expresses
      superoxide dismutase (SOD) mimicking activity. Examination was made of the
      effects of PS-K on cancer cell lines following administration of the anti-cancer
      drug cisdiaminedichloroplatinum (cisplatin). Cell proliferation of each cell line
      was inhibited markedly by cisplatin from 0.5 to 5 micrograms/0.5 ml per well.
      Fifty percent of the inhibitory concentration (IC50) was 0.33 micrograms/0.5 ml
      per well in NRK-49F and human ovarian cancer cells, and 1.5 micrograms/0.5 ml per
      well in H4-II-E. PS-K 50 micrograms/0.5 ml per well prevented cytotoxicity due to
      cisplatin toward NRK-49F, but enhanced the cytotoxicity on H4-II-E and human
      ovarian cancer cells. Increase in lipid peroxide and decrease in SOD activity
      were observed following an IC50 dose of cisplatin. With PS-K 50 micrograms/0.5 ml
      per well, all the above were augmented in H4-II-E and ovarian cancer cells, but
      diminished in NRK-49F cell line. PS-K may have effect on cancer patients through
      its combining with cisplatin.

PMID- 7719381
TI  - A heavy-chain grafted antibody that recognizes the tumor-associated TAG72
      antigen.
AB  - Murine anti-TAG72 antibodies react with more than 85% of human colorectal,
      gastric and ovarian carcinomas. However, the therapeutic utility of murine
      antibodies in human is severely restricted by their immunogenicity. The
      construction of humanized antibodies can potentially circumvent this problem. The
      latter antibodies can be generated by grafting CDRs from a murine antibody onto
      human immunoglobulin FRs followed by combining the resultant product with human
      immunoglobulin constant regions. In this study, we constructed a heavy-chain
      humanized anti-TAG72 antibody that we designated hmM4. This was achieved by the
      transplantation of CDRs from the murine VH of the ccM4 antibody into FRs of the
      human myeloma protein NEWM. The humanized antibody hmM4 retained its binding
      reactivity for the TAG72 antigen as measured by ELISA and Western blotting
      analysis respectively. However, it showed considerably less immunoreactivity for
      the TAG72 antigen than the original chimeric antibody ccM4. These results
      indicate that the murine anti-TAG72 specificity can be grafted to human
      immunoglobulin, and that the choice of the human immunoglobulin framework for the
      grafted antibody may be critical in maintenance of the immunoreactivity.

PMID- 7719383
TI  - Antitumor effect of exogenous/endogenous TNF (EET) therapy with cyclophosphamide
      on C6 glioma in rat.
AB  - We earlier reported that endogenous TNF could be induced in mice as well as in
      patients by successive administration of exogenous TNF as a primer and OK-432 as
      a trigger, and we termed this exogenous/endogenous TNF (EET) therapy. We studied
      the effect of EET therapy with cyclophosphamide (CY) on tumor-transplanted rats.
      In order to induce endogenous TNF, 5 x 10(5) U/kg of recombinant human TNF-S(AM2)
      (rTNF; 5.6x10(6) U/mg protein) was injected intravenously (iv) as a primer
      followed by injection of 25 KE/kg of OK-432 as a trigger. TNF activity induced in
      serum was about 500 U/ml. Only 1 U/g of TNF was detected in the brain. To
      evaluate the antitumor effect, C6 glioma cells (1.6 x 10(4) cell/5 microliters)
      was transplanted into the brain. On day 7 of the transplantation, the rats were
      administered iv with CY (75 mg/kg), treated with EET therapy 7 days thereafter,
      and survival days were checked. No clear difference in survival days was observed
      between the rats treated with the EET and the control group. Three rats out of 6
      treated with CY survived for more than 40 days, and all the rats treated with the
      combination of CY and EET continued to survive. The histological examination on
      day 44 revealed necrotic changes at the tumor lesions in all of the surviving
      rats, and the animals were evaluated as completely cured. These results suggest
      that applied treatment based on the EET therapy will be also effective against
      malignant brain tumors.

PMID- 7719385
TI  - Food intake and energy expenditure in obese female bingers and non-bingers.
AB  - Since compulsive eating occurs in approximately 30% of obese females and is
      associated with earlier relapse following weight loss, we compared daily energy
      intake, dietary composition and energy expenditure among obese binge eaters and
      obese non-bingers. Nine obese bingers (33 +/- 4 yrs, 95 +/- 6 kg, 39 +/- 1% fat)
      and nine obese non-bingers (47 +/- 3 yrs, 93 +/- 5 kg, 40 +/- 1% fat) were
      admitted for 12 days to a metabolic unit. Binge eaters were defined as scoring >
      25 on the binge eating scale (BES). During the initial 8 days, subjects ate ad
      libitum from two computerized vending machines offering a variety of foods and
      beverages. A weight maintenance diet was then provided for the next 4 days.
      Twenty-four hour energy expenditure (24EE) and respiratory quotient (24Q) were
      measured on the last day of both feeding periods in a respiratory chamber. Obese
      bingers showed a wider range of energy intake compared to non-bingers, but the
      mean daily energy intake was similar between the two groups (2587 +/- 454 vs 2386
      +/- 201 kcal/d) during 8 days of ad libitum intake. 24EE was not different
      between bingers and non-bingers after 8 days of ad libitum intake (2298 +/- 147
      vs 2109 +/- 97 kcal/d, P = 0.3) or 4 days of weight maintenance diet, even more
      so after adjustment for differences in fat-free mass, fat mass and age. Resting
      metabolic rate, sleeping metabolic rate, and macronutrient intake and oxidation
      were also similar between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719384
TI  - Racial difference in body core temperature between Pima Indian and Caucasian men.
AB  - A low body temperature is associated with a low metabolic rate for a given body
      size and body composition. These two traits might have been assets in the history
      of a population subjected to cycles of feast and famine, but became part of an
      obesity-prone syndrome in our westernized society characterized by plenty of food
      and a sedentary lifestyle. We tested whether Pima Indians have lower body
      temperatures than Caucasians, a trait which might partly explain the high
      prevalence of obesity in this population. Twenty-five Pima Indian (28 +/- 6 yrs,
      87.8 +/- 22.8 kg, 29 +/- 9% body fat) and 25 Caucasian (30 +/- 5 yrs, 80.7 +/-
      18.4 kg, 22 +/- 11% body fat) men had body core temperatures measured by
      telemetry for 24 h while in a respiratory chamber. Mean daily body core
      temperature was 36.93 +/- 0.12 and 36.90 +/- 0.22 degrees C in Pima Indians and
      Caucasians, respectively. Since body core temperature during sleep (SLBCT)
      correlated with percentage body fat, a subset of 10 Pima Indians and 10
      Caucasians were pair-matched for body weight and percentage body fat. In this
      group, SLBCT was lower in Pima Indians than in Caucasians (36.45 +/- 0.10 vs
      36.65 +/- 0.27 degrees C; P < 0.01) and, ethnic group accounted for 20% of the
      variance in SLBCT (P < 0.01). Surprisingly, the lower SLBCT was not associated
      with a low metabolic rate and therefore does not seem to play a role in the
      etiology of obesity in Pima Indians.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719386
TI  - Cerebrospinal fluid and plasma concentrations of SRIH, beta-endorphin, CRH, NPY
      and GHRH in obese and normal weight subjects.
AB  - Numerous hypothalamic peptides are involved in the control of eating behaviour.
      We assessed plasma and cerebrospinal fluid (CSF) levels of SRIH, beta-endorphin
      (beta-EP), CRH, NPY and GHRH in a group of massively obese patients and in normal
      weight subjects. In the obese patients, CSF SRIH and beta-EP levels were
      significantly reduced and increased, respectively, compared with controls (20.6
      +/- 2.62, mean +/- s.e.m., vs 34.5 +/- 2.14 pg/ml, P < 0.05, for SRIH and 111.2
      +/- 5.00 vs 80.4 +/- 5.32 pg/ml, P < 0.001, for beta-EP). Considering the data of
      obese and control subjects altogether, SRIH and beta-EP concentrations correlated
      negatively and positively, respectively, with BMI values (r = -0.641, P < 0.005
      and r = 0.518, P < 0.05). No significant differences were observed in CSF levels
      of CRH, NPY and GHRH between obese and normal weight subjects, though GHRH levels
      were close to the assay sensitivity. CSF concentrations of CRH were positively
      correlated with those of SRIH in obese patients (r = 0.60, P < 0.05) and with
      those of NPY both in obese (r = 0.69, P < 0.02) and in control subjects (r =
      0.83, P < 0.005). Plasma levels of SRIH, beta-EP, NPY and GHRH did not differ
      significantly in the two groups of subjects; plasma CRH was undetectable. Our
      results argue against the hypothesis of an enhanced SRIH tone as the cause of
      impaired GH secretion in obese patients, a primary defect in GHRH or GH release
      seems more likely. Moreover, they emphasise the importance of an increased tone
      of endogenous opioids in the pathophysiology of human obesity.

PMID- 7719387
TI  - Weight variability in a population-based sample of older women: reliability and
      intercorrelation of measures.
AB  - Six measures of weight variability were examined in a cohort of 29,015
      postmenopausal women. Recalled weight at ages 18, 30, 40 and 50 years, current
      weight at baseline and at each of three biennial follow ups (approximate ages 62,
      64, 66, 68 years), and recalled episodes of intentional and unintentional weight
      loss were used to construct (1) the coefficient of variation (CV) in body weight,
      (2) weight change categories (cycling, weight gain, weight loss and stable
      weight), (3) the root mean square error of variation (RMSE) around the slope of
      weight versus age, (4) the number of intentional weight loss episodes of 5 or
      more pounds, (5) the number of unintentional weight loss episodes of 20 or more
      pounds and (6) a categorical measure of intentional and unintentional weight loss
      episodes of > = 20 lb. The nine-month test-retest reliability correlations for
      the measures of lifetime history of intentional and unintentional weight loss
      were 0.80 and 0.62, respectively. Correlations between the different weight
      variability measures were positive but weak, suggesting that they reflect
      different aspects of weight variability. The RMSE discriminated categorically
      defined cyclers from weight gainers, but the CV did not. The weight change
      categories were more sensitive to age-related weight changes than the CV or RMSE.
      Studies examining the relationship between weight variability and health outcomes
      need to include measures that distinguish intentionality, short-term versus long
      term variability, and the magnitude, direction, and frequency of weight change.

PMID- 7719388
TI  - Evaluation of weight reduction in a community intervention for cardiovascular
      disease risk: changes in body mass index in the Minnesota Heart Health Program.
AB  - This paper describes the effectiveness of the Minnesota Heart Health Program
      (MHHP) in modifying mean body mass index (BMI) in whole communities. The MHHP is
      a 13-year research and demonstration project designed to reduce cardiovascular
      risk. One member of each of three pairs of matched communities received 7 years
      of community intervention activities that included risk factor screening, mass
      media education, adult education classes, worksite interventions, home
      correspondence programs, school-based programs, restaurant programs, and point-of
      purchase education in supermarkets. Weight gain prevention was emphasized for all
      adults and weight loss was encouraged among those who were obese or who had
      elevated risk factors known to be responsive to weight loss (e.g., high blood
      pressure). A strong upward secular trend in weight was noted in all MHHP
      communities over time. Intervention effects were evaluated conservatively with
      community as the unit of analysis. This analysis showed no overall effect of the
      MHHP intervention program on mean BMI. However, a positive intervention effect
      was noted early in the intervention among those with elevated cholesterol or a
      history of obesity-related disease. Possible reasons for this relatively weak
      community effect are discussed, including secular forces overwhelming
      intervention effects, an intervention effort not sufficiently focused on obesity,
      ceiling effects for weight concern in a population that was highly aware of the
      issue at baseline, and inherent limitations in educational approaches for this
      recalcitrant public health problem.

PMID- 7719389
TI  - Influences of genes and shared family environment on adult body mass index
      assessed in an adoption study by a comprehensive path model.
AB  - The aim of this work was to explore the influences of the shared familial
      environment and the nonshared individual environment on body mass index in light
      of convincing evidence for genetic influence. A cross-sectional adoption design
      was used, including information on adult adoptees and their biological fathers
      and mothers, biological full siblings and paternal and maternal half siblings,
      and adoptive fathers and mothers. Body mass index (weight/height2) was derived
      from reported height and weight. A model of familial resemblance based on path
      analysis is used to test for effects of genetic influence and for effects of the
      environment shared among family members: transmission from the adoptive father
      and adoptive mother to the adoptee, from biological father and biological mother
      to biological children they reared, from the biological father to maternal half
      siblings, from the biological mother to paternal half-siblings, and among
      biological siblings who may have lived together. The model also incorporates
      effects of assortative mating of the biological parents and of the adoptive
      parents, of shared preadoptive environmental influences between the biological
      mother and the adoptee, and of selective placement of the adoptee. The estimated
      heritability was 0.34 (standard error 0.03). No parameter indicating effects of
      shared familial environment either before or after adoption, assortative mating,
      or selective placement was significant. There was strong evidence for genetic
      effects, and no evidence for any effects related to the shared family environment
      -all familial resemblance in adults can be attributed to genetic influences.
      However, more than half of the interindividual differences in body mass index is
      due to nonshared individual environmental influences.

PMID- 7719390
TI  - 34-day total fast in an adult man.
AB  - The aim of this work was to investigate the changes of cardiac performance by
      both electrocardiography (ECG) and echocardiography (ECHOc), in addition to
      anthropometric and hormonal variables before, during and after prolonged total
      fasting (TF) and re-feeding in an overweight adult man. Physical examination,
      laboratory and hormonal measurements, ultrasonographic study of body fat
      distribution, ECG and ECHOc study were performed before during and after 34 days
      of TF and after 17 days of isocaloric re-feeding. The subject was a 52-year old
      Caucasian who was overweight with increased abdominal fat content (BMI: 28.6; W/H
      ratio: 0.95) and increased levels of arterial systolic and diastolic blood
      pressure (SBP, DBP). HPLC measurements of urinary catecholamine levels (HPLC),
      ECHOc study of cardiac performance, ultrasonographic study of body fat
      distribution were performed. The subject starved for 34 days losing 22kg, but
      after that time he was compelled to re-feed because of nausea and severe
      vomiting. A marked ketosis (ketonuria > 1200mg/day) was already present after 6
      days of TF. After 17 days of TF norepinephrine (NE) and epinephrine (EPI) urinary
      levels showed a two-fold and nine-fold increase respectively, but they became
      undetectable at the end of TF. After 17 days of re-feeding catecholamine urinary
      levels were similar to those measured after 17 days of TF. After both TF and 17
      day isocaloric re-feeding we found a decrease of visceral fat content and W/H
      ratio reached the normal values for age-matched subjects (W/H ratio after TF:
      0.80, after re-feeding: 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719391
TI  - The reproducibility of reported height and body weight in repeated questionnaire
      surveys.
AB  - Reproducibility of reported height and weight were studied via repeated
      questionnaire surveys distributed to subjects within a year. Effects of the
      factors which might influence the reproducibility of these values were
      investigated. Although only about half of the subjects reported the same height
      and 30% the same weight on the second questionnaire, no change was found in
      average height and weight after a one year interval for both male and female
      subjects. The reproducibility decreased with age for both height and weight.
      Smokers tended to have lower reproducibility for height than non-smokers. The
      shorter subjects had lower height reproducibility than their taller counterparts,
      while heavier subjects had lower weight reproducibility than light subjects. It
      was observed that the lower the weight reproducibility, the lower the height
      reproducibility and vice versa. Reported height or weight figures ending in zero
      or five were more frequent than the expected 10% with low reproducibility.

PMID- 7719392
TI  - Dehydroepiandrosterone sulphate, body fat distribution and insulin in obese men.
AB  - Sex steroid hormones may be involved in determining body fat distribution in men.
      Recent evidence suggests that insulin may be an important regulator of sex
      hormones metabolism in men. Few data, however, are available on the relationship
      of dehydroepiandrosterone sulphate (DHEA-SO4), a major secretory product of the
      adrenal gland, to regional distribution of body fat or to insulin levels in men.
      We therefore examined the association of DHEA-SO4, total testosterone and free
      testosterone to waist-to-hip ratio (WHR) and to subscapular-to-triceps ratio
      (STR) in 34 obese, otherwise healthy men. In addition, we examined the relation
      between these sex steroid hormones and insulin response to an oral glucose
      tolerance test. DHEA-SO4 was significantly positively related to STR and
      significantly negatively related to insulin area. These associations remained
      significant after adjustment for age and obesity. Using multiple linear
      regression, DHEA-SO4 was independently related to both STR and insulin area.
      Without claiming any causality in the observed associations, we conclude that, in
      obese men, high DHEA-SO4 levels are related to centralized adiposity, while low
      DHEA-SO4 levels are related to hyperinsulinemia.

PMID- 7719394
TI  - Improvement of left ventricular morphology and function in obese subjects
      following a diet and exercise program.
AB  - The aim of this work was to compare left ventricular performance during weight
      reduction induced by either physical training and diet or diet alone. Forty-three
      moderately obese subjects received a hypocaloric diet of 800 kcal/d for 4 weeks;
      22 of them were also subjected to an exercise program. By means of
      echocardiography, left ventricular dimensions and systolic time intervals were
      determined. Heart rate and blood pressure were measured at rest and during
      exercise. The addition of physical training resulted in a more favourable change
      in weight loss (-8.3 vs -6.3 kg), heart rate (-14 vs -7 bpm), systolic (-17 vs -8
      mm Hg), and diastolic (-11 vs -6 mm Hg) blood pressure. Left ventricular mass
      (LVM) was diminished more pronounced by combined therapy (-10.0%) as compared to
      diet alone (-4.7%). Changes in LVM were correlated with weight loss but not with
      alterations in heart rate and blood pressure. Fractional shortening and mean
      circumferential fiber shortening velocity did not improve significantly whereas
      the ratio of preejection period/left ventricular ejection time (PEPi/LVETi) was
      shortened in the diet and diet plus exercise group by -10.7 and -17.9%,
      respectively. It was concluded that exercise training in combination with a
      hypocaloric diet reduces left ventricular dimensions, LVM and PEPi/LVETi more
      distinctly than diet alone.

PMID- 7719393
TI  - Physical activity and body fatness in pre-school children.
AB  - The aim of this work was to investigate the relationship between levels of
      physical activity and body fatness in a group of pre-school children. A cross
      sectional study was carried out, physical activity being assessed as the ratio of
      total energy expenditure/basal metabolic rate (TEE/BMR) and TEE minus BMR. TEE
      was measured by the doubly labelled water technique, BMR was predicted from body
      weight. Body fat content was assessed from measurements of total body water via
      stable isotope dilution. The subjects were 93 children, aged between 1.5 and 4.5
      years, in South East England. Measurements of TEE were successful in 77 children.
      The correlation coefficient between the physical activity level (PAL) values and
      percentage body fat (sexes combined) was -0.52 (t = 5.3; P < 0.001). This figure
      indicates that a high level of body fat is associated with a low PAL value and
      that lower levels of body fat are associated with high PAL values. The
      correlation coefficient between TEE-BMR and percentage body fat was -0.51 (t =
      5.1; P < 0.001). It was concluded that low levels of physical activity in pre
      school children are associated with raised levels of body fat.

PMID- 7719395
TI  - Effect of modest weight loss on changes in cardiovascular risk factors: are there
      differences between men and women or between weight loss and maintenance?
AB  - The aim of this work was to determine whether the effects of weight loss on
      coronary heart disease (CHD) risk factors are comparable in men and women and
      whether the long term impact of modest weight loss is as great as the initial
      response. Changes in CHD risk factors were examined at 6 month intervals in 159
      moderately overweight subjects who were participating in an 18 month behavioral
      weight loss program. Men experienced greater decreases in blood pressure,
      triglycerides, and waist-to-hip ratio (WHR) and greater increases in HDL
      cholesterol with weight loss than women. Most of these gender differences were
      removed by adjusting for baseline values and changes in BMI. After these
      adjustments, improvements in WHR at 18 months were shown to be greater in women
      than in men. Participants (n = 39) who lost 4.5 kg or more from baseline to 6
      months (mean weight loss of 11.8 kg or 13% of initial body weight) and maintained
      this weight loss within +/- 2.3 kg had significant long term improvements
      (through 18 months) in triglycerides, HDL and LDL-cholesterol, WHR, systolic and
      diastolic blood pressure, and fasting and 2 h insulin. Changes in HDL
      cholesterol, the HDL:Total cholesterol ratio, and WHR actually increased between
      6 and 18 months and improvements in all other parameters were maintained over
      time. Men have greater improvements in CHD risk factors with weight loss than
      women, but this gender difference appears to derive from differences in CHD risk
      factors at baseline and differences in weight loss.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7719396
TI  - Commentary on Holman, Goldstein and Enas.

PMID- 7719398
TI  - Quality improvement in health care: the year behind, the year ahead.
AB  - In this special annual feature, Editorial Advisory Board members of The Joint
      Commission Journal comment on significant developments, issues, and trends in
      health care quality and quality improvement. With health reform in suspended
      animation, the field of health care quality marches on. Yet the critical
      questions and challenges loom larger than ever.

PMID- 7719397
TI  - Using patient focus groups for new patient services.
AB  - BACKGROUND: This article is intended to illustrate the usefulness of patient
      input in the strategic planning process and to demonstrate in particular the use
      of focus groups in concept development, concept testing, and program evaluation.
      INTERACTIVE PLANNING: Three areas of patient services were designed partly on the
      basis of patient input. "Service Teams with Appropriate Resources" (STARs) were
      conceived as basic organizational units to deliver interdisciplinary care to meet
      the needs of specific groups of patients. A patient services "menu" was
      envisioned to allow the patient or caregiver to decide which service would most
      appropriately and efficiently meet patient needs. The "Service Expectation
      Program" was formulated to ease entry into the hospital by providing information
      on what patients should expect from the hospital experience. CONCEPT TESTING:
      Focus groups were used again to test and refine the concepts developed during the
      interactive planning stage. General themes included the need for improved
      communication, the desire to be treated with respect and dignity (personhood),
      the need for coordination across the continuum of care, and the desire for more
      personal choice and control. ONGOING EVALUATION: Sources of patient feedback used
      in the ongoing evaluation process included a patient satisfaction survey and a
      telephone survey. Additional focus groups and telephone surveys are planned.
      MANAGEMENT ISSUES: The focus group discussions with patients introduced useful
      data into the quality improvement and interactive planning process. Findings were
      disseminated to all levels of hospital management and program staff through
      newsletters, reports, and in-service training sessions. Data were useful in
      interactive planning, program concept testing, and the development and
      implementation of new services.

PMID- 7719399
TI  - Nurses leading the charge to take national AHCPR guidelines into local settings.

PMID- 7719400
TI  - The paradox of guideline implementation: how AHCPR's depression guideline was
      adapted at Kaiser Permanente Northwest Region.
AB  - BACKGROUND: To ensure implementation, the Agency for Health Care Policy and
      Research's (AHCPR) Guideline for the Treatment of Depression in Primary Care was
      recently translated into a local document by a large health maintenance
      organization (HMO). The guideline revision process was studied on the basis of
      interviews with members of the guideline revision committee and others,
      observation of meetings, and documents and correspondence. WHY THE GUIDELINE WAS
      CHANGED: The HMO changed the AHCPR guideline for reasons of convenience,
      credibility, audience, purpose, and context. For example, in their roles as
      representative consumers, committee members perceived that the AHCPR guideline,
      although addressed to primary care clinicians, was actually written from a
      psychiatric perspective and based on a psychiatric literature not relevant to
      primary care. COMPARISON OF THE GUIDELINES: Although the guidelines differ
      dramatically in length and format, coverage, emphasis, and organizing principle,
      substantive conflict between the two guidelines' recommendations is minimal. For
      example, the emphasis on medication is greater in the adaptation, which adds
      considerable original material of a practical nature on drugs and drug use. In
      addition, the original guideline has a "research literature orientation." In
      contrast, the adaptation is described as "clinical decision oriented",
      identifying the key actions and decisions that a practicing clinician must make
      to treat depression. DISCUSSION AND IMPLICATION: Translation of science-oriented
      national guidelines into user-oriented documents tailored to local audiences and
      settings can add great value to the guideline development process without
      sacrificing science-derived integrity-and is probably essential to successful
      implementation.

PMID- 7719402
TI  - A case of primary Hodgkin's disease of the stomach.
AB  - A case of primary Hodgkin's disease, a lymphocyte-predominant entity, occurring
      in the stomach is described. The patient was a 37-year-old man who complained of
      general fatigue. Endoscopic biopsy revealed gastric malignant lymphoma. Subtotal
      gastrectomy and postoperative chemotherapy following a modified CHOP regimen were
      performed. The patient has been free of recurrence during a follow-up period of
      15 months. The preoperative diagnosis of gastric Hodgkin's disease is difficult.
      Thus far, of 100 cases of gastric Hodgkin's disease reported in Japan, only 3
      were diagnosed correctly preoperatively. We also misdiagnosed our case, as B cell
      type malignant lymphoma, preoperatively. The final diagnosis of Hodgkin's disease
      of the stomach was made on the basis of histopathological and immunohistochemical
      examinations. Hodgkin's disease of the stomach is rare, and there are
      histologically similar diseases; Ki-1 lymphoma, adult T cell lymphoma, malignant
      histiocytosis, and infectious monocytosis. Careful diagnosis is essential thus
      for Hodgkin's disease of the stomach.

PMID- 7719401
TI  - Involvement of capsaicin-sensitive neurons in gastrin release provoked by
      intragastric administration of bile salts in the rat.
AB  - To clarify the mechanism of gastrin release provoked by the reflux of bile juice
      into the stomach, we studied the effects of tetrodotoxin (0.08 mg/kg), atropine
      sulfate (0.5 mg/kg), truncal vagotomy, and chemical denervation of afferent
      sensory neurons with capsaicin (100 mg/kg) on gastrin release induced by bile
      salts in the rat (n = 6 per group). Sodium taurocholate and deoxycholate (> 2.5
      mM) significantly increased the serum levels of gastrin. However, sodium
      tauroursodeoxycholate had no effect. The levels of serum gastrin before and 1 h
      after administration of 2.5 mM sodium taurocholate were 94.6 +/- 10.7 and 211.0
      +/- 21.1 pg/ml, respectively. Tetrodotoxin and atropine sulfate completely
      inhibited this sodium taurocholate induced-gastrin increase, while truncal
      vagotomy was without effect. Capsaicin markedly reduced the increasing effects of
      sodium taurocholate. These findings suggested that the neuronal pathways involved
      in gastrin release are probably an intragastric local circuit originating from
      capsaicin-sensitive afferent sensory neurons and terminating in muscarinic
      receptors in the postsynaptic efferent cholinergic neuron system.

PMID- 7719403
TI  - Case report of a patient with multiple lesions of the stomach, including multiple
      cancers and an adenomatous polyp.
AB  - This paper describes an unusual case of an 80-year-old man followed up for
      multifocal gastric cancers. There were three separate polypoid carcinomas and one
      adenomatous polyp with no sign of malignancy. We measured the DNA content of the
      gastric cancer and adenomatous cells obtained from endoscopically biopsied
      specimens. The adenomatous polyp and one of the cancerous lesions showed DNA
      diploidy. The other two cancerous lesions showed DNA aneuploidy, with different
      DNA index (DI) values (1.12 and 1.64, respectively). It is considered that the
      three cancers arose from different stem lines. However, an operation was not
      performed because the patient refused gastrectomy, and therefore only
      conservative follow up has been continued. Presentation of this case is followed
      by a detailed discussion focusing on the possible development of carcinoma in
      gastric adenomatous polyps in view of the data from the literature.

PMID- 7719404
TI  - Small ileal neurofibroma causing intussusception in a non-neurofibromatosis
      patient.
AB  - Neurofibromas in the small intestine are usually accompanied by von
      Recklinghausen's disease (neurofibromatosis), and usually originate in the
      intramuscular plexus of Auerbach. We present here a solitary neurofibroma, which
      caused an ileocolic intussusception, originating in the submucosal plexus of
      Meissner in a non-neurofibromatosis patient. To our knowledge, there is no
      previous report of a neurofibroma originating in the plexus of Meissner. This
      condition was clearly confirmed by macroscopic and microscopic evaluation.

PMID- 7719405
TI  - Evolution of Mirizzi syndrome with biliobiliary fistula.
AB  - The mechanisms of fistula formation were analyzed in eight patients with Mirizzi
      syndrome with biliobiliary fistula. The fistula was type 1 in three patients and
      type 2 in five, according to the Corlette-Bismuth classification. The apparent
      mechanisms of fistula formation include inflammation of the gallbladder, its
      subsequent fusion to the bile duct, and increase in the internal pressure due to
      either contraction of the gallbladder or multiple stones. However, no
      predisposing conditions other than a longstanding history of cholelithiasis have
      been suggested. Differences in the type of fistula are considered to be due to
      the mode of fusion of the gallbladder to the bile duct, and the size of the
      perforation, which is apparently determined by the area in contact with the
      stone.

PMID- 7719406
TI  - Peptic ulcer and gastric acidity: a new look at an old aphorism, "the higher the
      ulcer, the lower the acidity".

PMID- 7719407
TI  - Omeprazole in the management of sclerotherapy-induced esophageal ulcers resistant
      to H2 blocker treatment.

PMID- 7719408
TI  - Simple and sensitive detection of K-ras gene mutations in human pancreatic
      cancers by nonradioisotopic single-strand conformation polymorphism analysis.

PMID- 7719409
TI  - Significance of rapid urease test for identification of Helicobacter pylori in
      comparison with histological and culture studies.
AB  - Helicobacter pylori in the stomach is an etiological factor of gastritis and
      peptic ulcer. It is now considered that gastric cancer can be, at least in some
      cases, a late complication of H. pylori infection. In 123 consecutive endoscopic
      antral biopsies obtained from patients with the Okamoto Hospital, the specimens
      were subjected to the rapid urease test (RUT), histology (H&E stain), and
      culture, for the identification of H. pylori. The results of these methods were
      compared semi-quantitatively in order to evaluate these detection methods for
      identifying H. pylori. The results of these methods were found to agree well,
      with the Spearman's rank correlation coefficient between RUT and culture being
      0.90 (P < 0.01) and that between histology and culture being 0.80 (P < 0.01). RUT
      is considered to be a very simple, sensitive, and highly specific test which
      enables the endoscopist to diagnose H. pylori infection.

PMID- 7719410
TI  - Elevation of ratio of urinary N-acetylneuraminlactose to free sialic acid in some
      advanced cancer patients.
AB  - We estimated the levels of free sialic acid and sialylated oligosaccharides
      excreted in the urine of normal donors (n = 10) and patients with gastric cancer
      (n = 6) and colorectal cancer (n = 4). The total sialic acid level in cancer
      patients was similar to that in normal donors. However, the ratios of
      glycosidically bound sialic acids to free sialic acid were higher in some
      advanced cancer patients than in the normal donors. A major component of
      sialylated oligosaccharides was N-acetylneuraminyl alpha (2-->3) lactose. The
      elevation of the urinary ratio of this sialylated oligosaccharide to free sialic
      acid observed in some advanced cancer patients in this study may reflect the
      elevation of sialyltransferase activity in tumor tissues.

PMID- 7719411
TI  - Detection of immunoreactive antigen, with a monoclonal antibody to measles virus,
      in tissue from a patient with Crohn's disease.
AB  - Using immunofluorescence (IF), we investigated reactive antigens present in
      Crohn's disease patients with monoclonal antibodies derived from cells infected
      with measles virus, but not with the subacute sclerosing panencephalitis virus.
      During immunoblotting, one monoclonal antibody (mAb 86) reacted with a
      polypeptide with a molecular weight of 36,000 dalton (M; matrix protein) in
      measles virus-infected cells. This monoclonal antibody displayed a positive
      reaction only with tissues from patients with Crohn's disease by the IF test. It
      did not react with samples from patients with other chronic inflammatory bowel
      diseases, such as ulcerative colitis. Other monoclonal antibodies to the measles
      virus protein, and monoclonal antibodies to Herpes simplex virus type 1 did not
      react with the same tissue samples. The role of measles virus infection and/or a
      viral antigen (possibly the M protein) as a causative agent in Crohn's disease
      poses a challenging avenue for further research.

PMID- 7719412
TI  - Effect of leukotriene C4D4 antagonist on colonic damage induced by intracolonic
      administration of trinitrobenzene sulfonic acid in rats.
AB  - We examined the effects of eicosanoid antagonists on colonic damage induced by
      trinitrobenzene sulfonic acid (TNB) in a rat inflammatory bowel model. TNB (30
      mg) dissolved in 0.25 ml of 50% ethanol, was given intrarectally. The appropriate
      doses of ONO-1078 (a leukotriene C4D4 antagonist), ONO-4057 (a leukotriene B4
      antagonist), and OKY-046 (a thromboxane A2 synthetase inhibitor) were given to
      obtain the same blood level, either 4 h before (pre-treatment model) or 24 h
      after (the post-treatment model) the administration of TNB (n = 8 in all groups).
      Drugs were given once daily for 6 days through a gastric feeding tube. Autopsy
      was performed on the 7th day. Colonic damage was assessed in terms of colonic
      damage scores, and myeloperoxidase (MPO) activity and eicosanoid concentrations
      in colonic tissues were measured. Compared with the group given TNB alone, the
      colonic damage score was reduced to 10% in the pre-treatment model with ONO-1078,
      but the score was not reduced in other groups, MPO activity was not changed in
      any group. The concentration of leukotriene C4 was reduced with ONO-1078
      treatment, in both pre- and post-treatment models. These results demonstrated
      that a leukotriene C4D4 antagonist reduced colonic inflammation; however, its
      anti-inflammatory effect was limited in this colitis model.

PMID- 7719413
TI  - Expression rate of cytokine mRNA in the liver of chronic hepatitis C: comparison
      with chronic hepatitis B.
AB  - This study was carried out to test the hypothesis that, in chronic hepatitis
      (CH), inflammatory processes, including viral replication, host immune response,
      and hepatocyte destruction, are regulated by a cytokine network in the liver.
      Expression of the mRNA of the cytokines IL1-beta, IL2, IL4, IL5, IL6, TNF-alpha,
      and IFN-gamma, the lymphocyte markers CD4 and CD8, and the HLA class I molecule,
      beta 2-microglobulin (B2MG) in the liver tissue of 20 CH(C) cases and 9 CH(B)
      patients was investigated by the reverse transcription polymerase chain reaction
      (RT-PCR) method. TNF-alpha, CD4, and B2MG mRNA were detected in 100% of cases of
      in both CH(B) and CH(C). The expression rates of IL1-beta, IL2, IL4, IFN-gamma,
      and CD8 mRNA were 80%, 40%, 25%, 40%, and 80% in CH(C) and 88.9%, 44.5%, 30%,
      55.6%, and 100% in CH(B). IL6 mRNA was detected only in CH(B), in 22.2% of cases,
      IL5 mRNA was not detected in either CH(B) or CH(C). IL2, IL4, and IFN-gamma mRNA
      were expressed significantly more frequently in patients who had high serum ALT
      and a high histological activity index (HAI) score. There was no difference in
      cytokine expression between CH(B) and CH(C), except in IL6, suggesting the
      existence of a common immunopathogenesis for CH(B) and CH(C). In chronic viral
      hepatitis, IL1-beta and TNF-alpha appear to play a major role in immune responses
      and IL2, IL4, and IFN-gamma seem to be associated with increased cytotoxic T cell
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719414
TI  - Expression of hepatocyte growth factor and transforming growth factor beta 1 mRNA
      in P. acnes and lipopolysaccharide-treated rats.
AB  - Hepatocyte growth factor (HGF), a potent hepatocyte mitogen in vitro, triggers
      hepatocyte regeneration after partial hepatectomy and acute liver cell necrosis
      induced by chemicals. In contrast, transforming growth factor beta 1 inhibits
      hepatocyte proliferation in vitro and suppresses liver regeneration in vivo. We
      assessed the expression of HGF and TGF beta 1 mRNA in an endotoxin-related
      hepatic cell necrosis model. Intravenous injection of Gram-negative
      lipopolysaccharide (LPS) into rats previously given heat-killed Propionibacterium
      acnes induced endotoxin-related hepatic cell necrosis. In this model, serum ALT
      began to rise to more than 100IU as early as 3 h after LPS injection, reaching
      300IU 12h after injection. HGF mRNA levels in the liver did not increase
      significantly until 5h after LPS injection; at 12h, they had increased about
      threefold compared with controls. TGF beta 1 mRNA expression increased threefold
      after P. acnes treatment alone and increased further after LPS injection. In the
      spleen, HGF mRNA levels increased within 3h, but in the lung no increase in HGF
      mRNA was observed. Early elevation of liver TGF beta 1 mRNA levels and delayed
      elevation of HGF mRNA levels, with low expression of HGF in the lung, may play a
      role in the pathogenesis of endotoxin-related hepatic necrosis.

PMID- 7719415
TI  - Evaluation of portal circulation through the superior mesenteric vein with an
      enteric capsule of [123I]iodoamphetamine.
AB  - We report a method by which the contribution of the superior mesenteric vein to
      the portal blood flow can be evaluated noninvasively. An enteric-coated capsule
      containing [123I]iodoamphetamine is given by mouth 3h before the examination. The
      data obtained are treated by computer to calculate the portal shunt index (SI)
      through the superior mesenteric vein. The SI was higher for more severe liver
      disorders, Increasing in the order of chronic persistent hepatitis, chronic
      aggressive hepatitis, and cirrhosis. The SI was higher in cirrhotic patients than
      in chronic hepatitis patients or healthy volunteers (both, P < 0.0001). The SI
      was higher in cirrhotic patients with esophageal varices than in such patients
      without varices (P < 0.05). The SI was higher in cirrhotic patients with ascites
      than in such patients without ascites (P < 0.001). The SI was higher in cirrhotic
      patients with encephalopathy than in those without encephalopathy (P < 0.01).
      Correlation was significant between the SI and classical indicators of functional
      reserve. This method is clinically useful.

PMID- 7719416
TI  - Increased bile acid concentration in liver tissue with cholesterol gallstone
      disease.
AB  - Patients with cholesterol gallstone disease have a reduced pool of bile acids.
      Overly sensitive feedback inhibition of bile acid synthesis has been postulated
      to explain this size reduction. To test this hypothesis, hepatic bile acid
      concentration and the activity of cholesterol 7 alpha-hydroxylase, the rate
      limiting enzyme for bile acid biosynthesis, were determined in ten patients with
      cholesterol gallstones and ten patients without gallstones. The bile acids
      present in liver tissue are the sum of those returning to liver and those newly
      synthesized in liver. If an overly sensitive feedback inhibition truly existed in
      our gallstone patients, a decreased concentration of hepatic bile acids would
      have been expected. However, patients with cholesterol gallstones had
      significantly higher total (143.3 +/- 25.5 vs 64.5 +/- 10.8 nmol/g liver, P <
      0.01), chenodeoxycholic (64.1 +/- 9.9 vs 29.8 +/- 5.4, P < 0.01), deoxycholic
      (22.8 +/- 10.9 vs 2.0 +/- 0.7, P < 0.05), and ursodeoxycholic acid (6.2 +/- 1.4
      vs 1.5 +/- 0.6, P < 0.01) concentrations than patients without gallstones. The
      activity of cholesterol 7 alpha-hydroxylase did not differ significantly between
      the two groups. Impaired hepatic transport or secretion of bile acids is strongly
      suspected in cholesterol gallstone patients. The findings of the present study
      showed no evidence of overly sensitive feedback inhibition of bile acid synthesis
      in cholesterol gallstone patients. Bile acid pool size may be affected by the
      inappropriate increase of hepatic bile acids rather than by overly sensitive
      feedback inhibition.

PMID- 7719417
TI  - Interferon and cyclosporin A in the treatment of fulminant viral hepatitis.
AB  - The prognosis of fulminant hepatitis due to non-A, non-B virus infection and
      acute reactivation of hepatitis B virus in HB carriers is generally poor, and the
      treatment of choice in Western countries is recognized as liver transplantation.
      In countries such as Japan where liver transplantation is not readily available,
      however, these intractable types of fulminant hepatitis have to be treated
      medically. Based on the assumption that persistent replication of causal viruses
      and enhanced host immune responses, especially cellular immunity, to eradicate
      the viruses are the key mechanism in progressive liver cell destruction and the
      poor prognosis, we attempted a combination treatment with interferon and
      cyclosporin A for these types of fulminant viral hepatitis. Subjects in the
      present study consisted of 1 patient with acute severe hepatitis without coma and
      13 patients with coma (13 with fulminant hepatic failure) due to non-A, non-B
      virus and acute reactivation of hepatitis B virus. The patients were given
      interferon-beta, 300 x 10(4) U daily, and cyclosporin A, at an initial dose of 3
      mg/kg, with tapering. Fourteen patients with coma received artificial liver
      support that we devised. The patient with acute severe hepatitis survived,
      showing histologically remarkable liver regeneration. Eight of the 14 patients
      with hepatic coma, all of whom were indications for liver transplantation
      according to the criteria of the King's College group, survived. Decreased
      transaminase level, increased liver volume, and histological liver regeneration
      were observed in all the survivors. The combination of interferon and cyclosporin
      A is worth attempting in fulminant hepatitis caused by non-A, non-B virus and
      acute reactivation of hepatitis B virus in HB carriers.

PMID- 7719418
TI  - Role of renal gamma-glutamyltransferase activity in hepatic utilization of
      exogenous glutathione.
AB  - The importance of renal gamma-glutamyltransferase activity in the hepatic
      utilization of exogenous glutathione (GSH) was evaluated by injecting GSH (1.67
      mmol/kg body wt) i.v. into bilaterally nephrectomized and sham-operated Sprague
      Dawley rats in which endogenous hepatic GSH had been decreased (0.20 +/- 0.01
      mumol/g liver vs 5.87 +/- 0.26 mumol/g liver in normal controls, mean +/- SD) by
      diethylmaleate (0.5 ml/kg body wt, i.p.). Hepatic GSH concentration 60 min after
      GSH administration was lower in the nephrectomized than in the sham-operated rats
      (0.87 +/- 0.25 mumol/g liver vs 3.08 +/- 0.81 mumol/g liver, P < 0.001), while
      plasma GSH concentration was higher in the former (4.61 +/- 1.07 mM vs 0.11 +/-
      0.06 mM, P < 0.001). In rats with intact kidneys which had been given a gamma
      glutamyltransferase inhibitor (acivicin, 25 mumol/kg body wt i.v.) prior to GSH
      administration, the hepatic GSH concentrations (1.11 +/- 0.49 mumol/g liver) were
      comparable to those obtained in the nephrectomized rats. When N-acetylcysteine
      (1.67 mmol/kg body wt, i.v.) was administered instead of GSH, the hepatic GSH
      concentrations were similar in nephrectomized and sham-operated rats (1.54 +/-
      0.23 mumol/g liver vs 2.22 +/- 0.58 mumol/g liver, NS). The gamma
      glutamyltransferase activity was much higher in the kidney than in the liver
      (4460 +/- 830 IU/kg body wt vs 14 +/- 7 IU/kg body wt). These results indicate
      that the kidney plays an essential role in the hepatic utilization of exogenous
      GSH through its high gamma-glutamyltransferase activity.

PMID- 7719419
TI  - Steatorrhea in Japanese patients with chronic pancreatitis.
AB  - Fecal fat excretion, fecal mass, fecal fat concentration, and the coefficient of
      fat absorption were evaluated in 31 normal Japanese subjects with a mean fat
      consumption of 61.8 g and compared with the values in 43 Japanese patients with
      chronic pancreatitis (CP) with a fat consumption of 40.2 g. Fecal fatty acids
      were analyzed by the gas chromatographic method. Fecal fat excretion by normal
      individuals was 1.7 +/- 1.0 (Mean +/- SD) g/day (range, 0.4-4.9 g/day).
      Steatorrhea was therefore defined as fecal fat excretion that exceeded 5.0 g/day.
      The patients with CP were divided into three groups: non-steatorrhea (fecal fat <
      5.0 g/day), chemical steatorrhea (fecal fat > or = 5 g/day and no appearance of
      fatty stool), and manifest steatorrhea (evaluated from the appearance of fatty
      stool). In addition, we investigated the correlation between fecal fat excretion
      and pancreatic exocrine function, obtained by the pancreozymin-secretin (or
      secretin) test in 24 controls and 30 CP patients. Fecal fat excretion by CP
      patients was 9.1 +/- 8.8 g/day, which was significantly higher (P < 0.01) than
      that of controls. There were 28 (65%) CP patients with steatorrhea. Of these, 15
      (35%) showed chemical steatorrhea and 13 (30%) manifest steatorrhea. In CP
      patients, the fecal mass (250.5 +/- 133.6 g vs control, 125.6 +/- 52.5 g), fecal
      fat concentration (3.40 +/- 2.16 g% vs control, 1.48 +/- 0.89 g%), and
      coefficient of fat absorption (77.3 +/- 20.2% vs control, 97.2 +/- 1.7%) all
      showed significant differences from the controls.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7719420
TI  - An experimental study of gastric mucosal blood flow in endotoxemia of the rat,
      with special reference to the vagus nerve and EDRF.
AB  - Gastric mucosal lesions are an important complication in endotoxemia. In order to
      define the role played by the vagus nerve and endothelial-derived relaxing factor
      (EDRF) in gastric mucosal blood flow, an investigation was carried out on four
      groups of rats: a control group; a group given lipopolysaccharide (LPS, 5 mg/kg);
      a group given gossypol-acetic acid (gossypol), which has an injurious effect on
      the vascular endothelial cell; and a group given L-NG-monomethyl arginine
      (LNMMA). Following the administration of acetylcholine and papaverine
      hydrochloride (via the splenic artery) and vagus nerve stimulation in all four
      groups of rats, the effects of vagus nerve stimulation and EDRF on the gastric
      mucosal blood flow were determined with a laser Doppler rheometer. In the LPS
      group, the gastric mucosal blood flow was decreased after acetylcholine
      administration and vagus nerve stimulation. This was also the case in the
      gossypol group. These findings suggest that inhibition of EDRF release may be
      responsible for the reduced gastric mucosal blood flow observed in endotoxemia.

PMID- 7719421
TI  - Analysis of zinc and other elements in rat pancreas, with studies in acute
      pancreatitis.
AB  - Determination of the concentration of certain elements makes it possible to
      investigate the physiology of the pancreas. We used X-ray fluorescence to
      determine the concentrations of zinc and other elements in the pancreas of normal
      (control) rats and those with cerulein-induced pancreatitis. Ten elements (Zn,
      Ni, Fe, P, Ca, Cl, S, K, Ti, and Mn) were detected in controls. In the early
      stage of acute pancreatitis, the pancreatic concentrations of Zn, Ni, Fe, and P
      were significantly decreased (P < 0.05) and those of Ca and Cl were significantly
      increased (P < 0.05), compared with control levels. However, levels of S, K, and
      Ti did not differ significantly from the control values. Mn was detected in only
      some samples. The serum levels of Zn and Fe were significantly elevated (P <
      0.05) in acute pancreatitis. These observations indicate that Zn and these other
      nine elements could play an important role in acute pancreatitis.

PMID- 7719423
TI  - Measurement of apolipoprotein A1 in cholesterol gallstones and gallbladder bile
      of patients with gallstones.
AB  - Biliary apolipoprotein A1 in bile inhibits the nucleation of cholesterol crystals
      from bile super-saturated with cholesterol. In the present study, using an enzyme
      linked immunosorbent assay of apolipoprotein A1, we determined the content of
      apolipoprotein A1 in cholesterol gallstones and samples of gallbladder bile
      collected simultaneously from 23 patients during cholecystectomy. Protein content
      in cholesterol gallstones ranged from 50 to 5700 micrograms/g, with median,
      quartile, and three quartile values being 250, 111, and 740; apolipoprotein A1
      content ranged from 9 to 9000 ng/g (200, 41, 647). The gallbladder bile samples
      contained protein at concentrations of 0.4-9.0 mg/ml (2.0, 1.1, 3.2), while
      apolipoprotein A1 was present at concentrations of 2.0-136.0 micrograms/ml (30.0,
      10.0, 90.0). A notable finding was that the A1/total protein (TP) values for
      gallbladder bile, which ranged from 0.13% to 6.80% (1.62, 0.89, 3.34), were
      several times higher than those determined for gallstone samples, which ranged
      from 0.01% to 1.2%, 2% (0.06, 0.02, 0.25). The results of sodium dodecylsulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that the protein
      profile in cholesterol gallstones was similar to that in gallbladder bile. It was
      concluded that: (1) the protein contained in gallstones may originate from bile,
      (2) the content of apolipoprotein A1 in cholesterol gallstones is only a trace
      amount, compared with that in gallbladder bile, and (3) biliary apolipoprotein A1
      may be retained in a soluble phase in gallbladder bile, with minimal
      precipitation onto the surfaces of gallstones.

PMID- 7719422
TI  - Pancreatic secretory trypsin inhibitor in human Brunner's glands.
AB  - Brunner's glands (duodenal glands) in humans are located mainly in the two
      proximal thirds of the duodenum. They are known to produce and secrete mucin. In
      recent years, human Brunner's glands have also been shown to express
      immunoreactivity toward epidermal growth factor-urogastrone (EGF-uro) and
      lysozyme. These proteins are considered to have a protective function within the
      gastrointestinal canal. Human pancreatic secretory trypsin inhibitor (PSTI) was
      recently identified in Brunner's glands. This present study was done by an
      immunohistochemical method, using monospecific polyclonal antibodies against
      human PSTI and human lysozyme, respectively. McManus/Alcian blue mucin staining
      was used to clarify the distribution of mucin. We found immunoreactive PSTI
      (irPSTI) in seven out of ten specimens. Lysozyme and mucin were present in all
      ten. While virtually all cells were stained for lysozyme and mucin, irPSTI was
      restricted to separate lobules and to cells in the ducts.

PMID- 7719424
TI  - [Radioactive aerosols formed by fires in regions polluted by products of the
      Chernobyl accident].
AB  - Fires during summer period of 1992 within 30-km zone near Chernobyl NPP lead to
      short-term increase of both 137Cs concentration in the air and ratios 137Cs/90Sr
      and 137Cs/238Pu as compared to quite conditions. The concentration of 137Cs
      resulted from the fires of various types was estimated. It was found that this
      value could exceed the maximum permissible concentration (MPC) for population if
      the soil contamination density was greater than 0.5 Ci/km2 and MPC for
      professionals at contamination density 7 Ci/km2. Fires lead to increase in
      inhaled radiation dose, whereas exposure dose rate remains unchanged.

PMID- 7719425
TI  - [Effects of hypomagnetic fields on motility of the cilia of ependymal cells in
      vivo].
AB  - The effect of reduced vertical component of geomagnetic field on motor activity
      of ciliate apparatus of ependymal cells in newborn rats in vivo has been studied.
      In has been shown that hypomagnetic field causes the inhibitory effect on the
      activity of ciliate apparatus up to absolute stoppage.

PMID- 7719426
TI  - [Effects of prolonged low-intensity radiofrequency radiation in cm-range on the
      development of subcutaneously grafted Ehrlich's adenocarcinoma].
AB  - White mongrel male mice with subcutaneously grafted Ehrlich adenocarcinoma were
      exposed at week intervals to three three-day sessions of low-intensity (5
      microWt/cm2) super short wave-therapy from two generators of oscillating
      frequency in the range of 2-18 GHz. As a result of treatment, the increase in
      tumour size was diminished, and the probability of its reverse development was
      increased, with animal lethality being decreased. During a month the recovery was
      increased from 0 to 50% in the first experiment and from 38.3% to 60% in the
      second. In the third experiment, the recurrence during a 72-day observation
      period was showed in none of the recovered mice.

PMID- 7719427
TI  - [Motor activity of rabbits in conditions of chronic low-intensity pulse microwave
      irradiation].
AB  - Motor activity of rabbits under daily thirty-minute irradiation (1.5 GHz, pulse
      duration 16 ms, pulse recurrence frequency 0.12 Hz, pulse intensity 0.3 mw/cm2)
      for one month was studied. From 14th day the reliable disadaptation changes such
      as an anxiety and alarm reaction were found. The importance of prolonged
      irradiation is noted.

PMID- 7719428
TI  - [Body's reaction to weakened geomagnetic field (the effect of magnetic
      deprivation)].
AB  - The data on the influence of weakened geomagnetic field on the embryonal
      development as well as nervous, endocrine and immune systems are presented. The
      possibility of biological effects modification under combined action of weakened
      geomagnetic field, ionizing radiation and electromagnetic fields in microwave
      range is discussed.

PMID- 7719429
TI  - [Changes in the secondary structure of DNA under the influence of external low
      intensity electromagnetic field].

PMID- 7719430
TI  - [Effects of low-intensity electromagnetic irradiation and endogenous peptides on
      isolated neurons of Helix lucorum].
AB  - In experiments with isolated neurones of molluscan Helix lucorum the effects of
      low intensity electromagnetic fields (EMF) and endogenous peptides on the
      transmembrane current dynamics was studied. A certain relationship between
      peptides and EMF effects was shown. Some features of primary mechanisms of EMF
      biological action were clarified.

PMID- 7719431
TI  - [Cellular effects of microwaves of thermal intensity].
AB  - The thermal and specific effects of cm range microwaves on cell systems was
      investigated. It was shown that cell damage (killing and permeability
      disturbance) in Escherichia coli B/r, Escherichia coli Bs-1, Saccharomyces
      cerevisiae and ACE were induced by microwave heating more effectively than by
      equivalent thermal heat.

PMID- 7719432
TI  - [Response of neurons of the sensomotor region of the cerebral cortex to low
      intensity pulsed ultra-high frequency irradiation].
AB  - A peculiarity of the work is an analysis of bioelectrical activity of single
      neurones under irradiation with low-level pulsed microwaves (6 GHz, 50 Hz, 0.2
      mW/cm2). A specially designed micromanipulator made of organic glass was used.
      The results are presented in comparison with appropriate reactions of neurones to
      other physical factors considered like microwaves as weak stimuli for central
      nervous system.

PMID- 7719433
TI  - [Total bioelectric activity of various structures of the brain in low-intensity
      microwave irradiation].
AB  - In experiments with thirty rabbits the influence of thirty-minute microwave
      irradiation (1.5 GHz, pulse intensity 0.3 mW/cm2; pulsed modes: 0.12 Hz, 16 ms or
      1000 Hz, 0.4 ms; pack-pulsed mode: pulse frequency 1000 Hz, pack frequency 0.12
      Hz) on the total bioelectrical activity of brain structures was studied. The
      reliable effect was detected only in hippocamp. The total bioelectrical activity
      of cortex, caudate nucleus, hypothalamus, amygdala and septum was not changed
      reliably in animal group studied. The reaction of hippocamp was displayed as
      amplification of theta-range in spectrum within of normal functioning.

PMID- 7719434
TI  - [Evaluation of changes in electrophysiological and hormonal parameters in rabbits
      resulting from short-term low-intensity ultra-high-frequency irradiation].
AB  - The paper is devoted to study of the influence of short-term low-level microwave
      irradiation (6GHz, modulation 2 Hz, average intensity 0.015 mW/cm2, exposure time
      50 min) on some electrophysiological and hormonal parameters in rabbits. No
      reliable changes in cardiac and respiratory rhythms, electromyogram intensity as
      well as cortisol, testosterone, insulin and thyroxine level in rabbits' blood
      were found.

PMID- 7719435
TI  - [A comparison of conditioned avoidance reflex in rabbits formed under the
      influence of permanent magnetic fields, ultra-high-frequency irradiation, light
      and sound].
AB  - Low-level microwaves (6GHz, 50 Hz, 0.2 mW/cm2) as well as magnetic field (1000
      Oe) can become conditioned stimuli for rabbits. The similar reflexes formed under
      influence of magnetic field, microwaves, light and sound comparable by biological
      importance as weak stimuli were compared. Similarity and distinctions in
      formation of stimulus-response connections under influence of penetration and
      adequate stimuli are discussed.

PMID- 7719437
TI  - [Characteristics of etiology of immediate hypersensitivity in conditions of
      exposure to infrasound].
AB  - The development of immediate hypersensitivity is process strictly specific for
      given allergen. The reaction with fatal outcome in guinea pigs is reproduced by
      80-100%. However, the work has been published recently in which an opportunity to
      influence the effect of antigen by non-ionizing physical factors was considered.
      In experiments with 230 guinea pigs the model anaphylactic shock was used.
      Animals were subjected to infrasound of 10 Hz frequency and 155-160 dB intensity
      for ten minutes just before antigen introduction. About 50-60% of animals were
      wrecked under combined sensitizer and infrasound influence. At the same time in
      control experiments 80-100% of animals were wrecked three minutes after
      introduction of permitted dose of sensitizer. The experiments under changed
      conditions as well as series with passive sensitization have shown that the
      infrasound effect is due to deviations (rejections) in specific part of
      anaphylactic shock.

PMID- 7719436
TI  - [Protective action of mexamine and indralin in intensive electromagnetic
      irradiation of rats].
AB  - Protective properties of radioprotectors from indolyl alkylamine group (mexamine
      and indralin) in rats exposed to powerful electromagnetic irradiation (2.4 GHz,
      specific absorption rate 90-100 W/kg) was studied. The survival index of tested
      animals reached the maximum in condition of prophylactic administration of drugs
      in intervals 20-60 minutes before irradiation. Protective effect of mexamine and
      indralin connected with hypothermia and desensitization conditioned by the drugs
      use.

PMID- 7719438
TI  - [Immune status of adult population of the Bryansk region living in territory
      polluted by radionuclides].
AB  - Clinical and immunological investigation with immune status evaluation of three
      groups of adult population of Bryansk Region was performed. The first group
      included 165 persons living in Vyshkov (settlement of town type in Bryansk
      Region) contaminated with radionuclides as a result of Chernobyl accident. The
      second group included 68 persons living in Vyshkov, immunological monitoring of
      those was performed. The third group consisted of 114 persons living on the
      "clean" area of Pochep (Bryansk Region). On both areas (contaminated Vyshkov and
      "clean" Pochep) the large percent of persons (three quarters of all investigated
      ones) had clinical manifestations of immune deficiency. The immune status of
      Vyshkov inhabitants was characterized by T-helper/inductor activation. That was
      expressed in significant increase of CD4+, CD4+/CD8+ in comparison of control
      group of primary donors and to "clean" Pochep inhabitants and in stable decrease
      of average values of serum IgG in comparison to control group, IgG and IgM in
      comparison to Pochep group. Maximum high values of T-helpers under lowest T
      suppressor/killer values were observed at clinical symptoms which may be
      stipulated by radiation factor (loss of hair and teeth, surplus weight,
      predisposition to bleedings) and in persons working in cattle-breeding.

PMID- 7719439
TI  - [Estimation of soil fraction of Pu in the formation of irradiation dose of
      inhabitants of the Bryansk region].
AB  - The estimation of plutonium in soils of the contaminated after Chernobyl accident
      areas of Bryansk Region (Russia) are presented. On the basis of data about Pu
      concentrations in soils and by means of migration models in "soil-man" system the
      doses received were assessed. Pu-239, 240 and Pu-238 were determined in samples
      of autopsy material (lung, liver, bones and tracheobronchial lymph nodes) of
      residents from Chernobyl-fallout contaminated regions. Effective doses have been
      obtained by means of data about Pu-concentration in autopsy samples.

PMID- 7719440
TI  - A new theory of enterorecirculation of amino acids and its use for depleting
      unwanted amino acids using oral enzyme-artificial cells, as in removing
      phenylalanine in phenylketonuria.
AB  - Oral binders remove intestinal bile acid and prevent its reabsorption and
      recycling thereby lowering systemic cholesterol levels. The results in this paper
      demonstrate the presence of another extensive enterorecirculation for amino
      acids. Pancreatic and other glandular secretions into the intestine contain large
      amounts of proteins, enzymes and polypeptides. Tryptic digestion converts these
      into amino acids which are then reabsorbed back into the body as they pass down
      the intestine. This paper shows that this forms a large enterorecirculation of
      amino acids between the body and intestine. The dietary protein source of amino
      acids is negligible when compared to the endogenous source, since this paper
      shows that protein-free diet did not alter the intestinal amino acid
      concentration. This raises the possibility of using this for the selective
      depletion of specific body amino acids. In this paper we use a phenylketonuria
      (PKU) model in rats to test the use of this hypothesis. In PKU rats, artificial
      cells microencapsulated phenylalanine ammonia lyase (PAL) given orally is more
      effective than a phenylalanine-free diet. The enzyme artificial cells are more
      efficient in lowering PHE in the intestine, plasma and cerebrospinal fluid.
      Compared to PKU on PHE-free diet, this has resulted in better weight gain and
      general physical condition. Preliminary studies also show that artificial cells
      microencapsulated asparaginase, glutaminase and tyrosinase given orally can
      deplete the corresponding amino acid from the intestine.

PMID- 7719442
TI  - Mathematical modelling of immobilized animal cell growth.
AB  - A two-dimensional mathematical model for animal cell growth was employed to study
      the suspension, as well as stationary, culture of micro-encapsulated and gel
      immobilized animal cells. For stationary microcapsules with low-viscosity
      intracapsular liquid, it was found that capsule radius, capsule loading and
      medium-change time have the most significant effects on the intracapsular cell
      density. The model was also adapted to simulate other scenarios of cell growth
      such as in gel beads and suspended microcapsules. The simulated time course of
      oxygen concentration and specific growth rate revealed a complicated interaction
      between material transport and cell growth kinetics. With the mass transfer
      coefficient for oxygen transfer (KLa') into the medium equal to 4.0 hr-1, for
      instance, it was found that the specific growth rate of the microencapsulated
      cells was controlled by the supply of glucose and oxygen. When the value of KLa'
      was reduced to 0.6 hr-1, however, oxygen supply appeared to be the sole factor
      affecting the specific growth rate. In the case of suspended gel beads, a
      simulation revealed a higher cell density towards the gel bead surface. The
      transport of nutrients and oxygen to the central region of the gel bead was
      apparently blocked by the surrounding cells.

PMID- 7719441
TI  - In vitro evaluation of heparin adsorption during haemoperfusion with Dowex 1 x 2
      anion exchange resin.
AB  - Haemoperfusion treatments have found clinical applications in various
      pathologies, even though problems due to the insufficient biocompatibility of
      sorbents have often limited its employment. Among these problems, there is that
      of heparin adsorption which can determine coagulation disorders or the necessity
      of a dosage correction during the extra corporeal circulation. The aim of the
      study was to test the influence of different methods of coating on heparin
      adsorption from an anion exchange resin coated with poly-hydroxyethyl
      methacrylate. Eight haemoperfusion cartridges were prepared using 8 g of resin
      for each (4 cartridges contained resin coated by spray-coating technique and 4
      coated by phase-separation one). Haemoperfusion was performed by using 600 IU of
      heparin (25,000 IU) corresponding to 0.12 ml in 500 ml of swine blood and a
      closed circuit. Blood flow rate was maintained at 15 ml/min and the circuit
      pressure was 70 torr during haemoperfusion. Blood samples were withdrawn at timed
      intervals before and after the column in order to evaluate blood heparin levels.
      The results demonstrated the superiority of the phase-separation technique that
      does not permit any interactions between adsorbent substance and drug. As a
      result of this, the adjustment of the dosage may not be necessary during further
      in vivo experiments.

PMID- 7719443
TI  - Haemolytic properties of pluronic surfactants and effects of purification.
AB  - The effects of incubating blood from mice, rats, rabbits or hamsters with either
      a commercial grade or a silica-purified fraction of Pluronic F-68 or Pluronic F
      38 have been studied. Incubation of blood with up to 4.0% (w/v) of commercial or
      purified Pluronic F-68 produced no detectable haemolysis (< 0.1%). Haemolysis did
      occur with concentrations of commercial Pluronic F-68 above 4.0% (w/v). This was
      maximal with rat blood incubated with 10.0% (w/v) Pluronic F-68, where the mean
      haemolysis was 4.7 +/- 1.5%; the mean haemolysis in rat blood was reduced to 0.5
      +/- 0.3% (P < 0.05) following incubation with the purified Pluronic F-68
      fraction. Neither commercial grade or purified Pluronic F-38 produced any
      significant haemolysis when incubated with rat or hamster blood. Incubation of
      rabbit blood with 10.0% (w/v) commercial Pluronic F-38 produced only 0.5%
      haemolysis.

PMID- 7719444
TI  - Diffuse optics determination of hemoglobin derivatives in red blood cells and
      liposome encapsulated hemoglobin.
AB  - High resolution optical absorption spectra of hemoglobin derivatives in red blood
      cells and phosphatidylcholine liposomes were calculated from diffuse reflection
      and transmission spectra by means of the one-dimensional diffusion approximation.
      The numerical technique of singular value decomposition was used to calculate the
      composition of red cell and liposome mixtures.

PMID- 7719445
TI  - Resuscitation with Diaspirin Crosslinked Hemoglobin in a pig model of hemorrhagic
      shock.
AB  - The efficacy of Diaspirin Crosslinked Hemoglobin (DCLHb) as a resuscitative fluid
      in hemorrhagic shock was compared to another colloid solution (human serum
      albumin, HSA) and a crystalloid solution (Lactated Ringer's, LR). Hemorrhage (35
      mL/kg) was followed by isovolemic exchange then volume replacement. This modeled
      the clinical situation where resuscitative fluids are administered prior to
      stopping the hemorrhage, the hemorrhage is stopped, then blood volume is
      restored. Four combinations of resuscitative fluids were evaluated during
      isovolemic exchange: volume replacement: DCLHb:LR, HSA:LR, HSA:HSA and LR:LR. All
      doses were 10 mL/kg:35 mL/kg except LR:LR which was 10 mL/kg:125 mL/kg. Volume
      replacement was followed by a stabilization period and reinfusion of shed blood
      (35 mL/kg). MAP increased most rapidly using DCLHb (from 48 to 102 mmHg after 10
      min of isovolemic exchange) and was maintained for at least 2 hours. Arterial
      oxygen content and acid-base status were significantly improved after
      resuscitation with DCLHb:LR vs. other resuscitative therapies. In conclusion,
      DCLHb:LR was an effective resuscitative therapy in treatment of hemorrhagic
      shock.

PMID- 7719446
TI  - Characterization of Gallus domesticus alpha-N-acetyl-galactosaminidase blood
      group A2 activity.
AB  - Soluble A antigens and an enzyme-linked immunosorbent assay (ELISA) using type A2
      erythrocyte membranes were used to study the activity of an alpha-N-acetyl
      galactosaminidase from Gallus domesticus (domestic chicken). The enzyme readily
      hydrolyzed the terminal N-acetyl-alpha-D-galactosamine of the A antigen under a
      variety of conditions, converting it to H antigen. Conversion of the A antigen to
      H antigen produces blood type O, which is universally transfusable. These
      preliminary studies are important in determining optimal conditions for enzymatic
      conversion of blood type A to O if efficient large scale production of
      enzymatically converted, universally transfusable red blood cells is to be
      achieved.

PMID- 7719447
TI  - In vitro drug release of antibiotic-loaded porous hydroxyapatite cement.
AB  - A model was proposed for describing the observed in vitro release behavior of
      drugs from porous HAPs. The model consists of three successive stages; during the
      first stage, the dissolution medium penetrating into the porous HAP, the amount
      of the drug released is proportional to the square root of release time. During
      the second stage, after the pores in the HAP are filled out by the dissolution
      medium, the drug release being proceeded by dissolution into the dissolution
      medium outside of the HAP, the amount of the drug released is proportional to
      release time. During the third stage, after the drug concentration is decreased
      and below the solubility limit of the drug in the dissolution medium, the drug
      diffusing to the stirred dissolution medium outside of the HAP, the release rate
      is markedly slowed and the release amount approaches a plateau value.

PMID- 7719448
TI  - Diaspirin crosslinked hemoglobin (DCLHb) does not affect the anesthetic potency
      of isoflurane in rats.
AB  - Hemoglobin solutions are being developed as oxygen carrying fluids for multiple
      clinical indications. Despite an early report of accentuation of ether
      anesthesia, the effect of hemoglobin on anesthetic potency has not been assessed.
      We assessed the effect of alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) on
      the anesthetic requirement of isoflurane necessary to keep rats unresponsive to
      noxious stimuli (1.0 MAC [minimum alveolar concentration]). During isoflurane
      administration, each rat received one of the following fluid regimens: 44Hct/N
      normal hematocrit and volume; 44Hct/H-8.0 ml of donor blood given as a
      hypervolemic bolus; 30Hct/H-5.0 ml of DCLHb given as an exchange transfusion and
      8.0 ml as a hypervolemic bolus; or 16Hct/H-15.0 ml of DCLHb given as an exchange
      transfusion and 8.0 ml as a hypervolemic bolus. MAC was determined using a
      standard tail clamp technique. The isoflurane requirement to achieve 1.0 MAC was
      not different between the four groups. These results are consistent with a
      hypothesis that DCLHb does not change the anesthetic state.

PMID- 7719449
TI  - 18th International Symposium on Column Liquid Chromatography. Part II.
      Minneapolis, Minnesota, 8-13 May 1994.

PMID- 7719450
TI  - Use of high-performance liquid chromatography-diode array detection in forensic
      toxicology.
AB  - A comprehensive approach to the analysis for many drugs in postmortem blood and
      biological fluids using high-performance liquid chromatography and diode array
      detection has been developed. To reduce the likelihood of co-eluting interference
      components of postmortem blood or other drugs, selective back-extraction was also
      used to screen and quantitate drugs in blood and biofluids. An isocratic mobile
      phase (acetonitrile, phosphoric acid and triethylamine buffer, pH 3.4) was
      developed and found stable, reliable and convenient for general drug screening
      and quantitation. A library of drug spectra in the ultraviolet wavelength range
      (210-367 nm) was established for 272 drugs on two reversed-phase columns:
      Supelcosil (biphenyl) and LiChrospher RP-8. The application of several methods to
      whole blood, the analysis of complex cases and the use of multicomponent analysis
      for qualitative and quantitative analysis is discussed.

PMID- 7719451
TI  - Liquid chromatographic determination of the macrolide antibiotics roxithromycin
      and clarithromycin in plasma by automated solid-phase extraction and
      electrochemical detection.
AB  - A liquid chromatographic method for the determination of the macrolide
      antibiotics, roxithromycin and clarithromycin, in plasma is described. The method
      is fully automated, employing on-line solid-phase extraction for sample clean-up,
      using the Prospekt unit. Plasma samples, mixed with internal standard, were
      injected onto exchangeable CN cartridges. After washing, the compounds were
      eluted and transferred to a C18 analytical column for separation and
      electrochemical detection. Clarithromycin was used as internal standard when
      assaying roxithromycin and vice versa. The recovery of the solid-phase extraction
      method was 90% and higher, and the relative standard deviation was about 3%. The
      limit of quantitation was 0.5 mumol/l when 25 microliters of plasma was injected.
      Comparison with a liquid-liquid extraction method for sample clean-up showed good
      agreement.

PMID- 7719452
TI  - Analysis of mycolic acids by high-performance liquid chromatography and
      fluorimetric detection. Implications for the identification of mycobacteria in
      clinical samples.
AB  - Mycolic acids from Mycobacterium phlei and M. bovis cell wall skeletons (CWSs)
      were analyzed by HPLC. After saponifying lyophilized CWSs in methanolic KOH, the
      mycolic acids were quantitatively extracted into chloroform. Aliquots of the CWS
      mycolic acid extracts were then derivatized prior to HPLC analysis with a UV
      reagent, p-bromophenacylbromide (PBPB), and three fluorescent reagents, 4
      bromomethyl-6,7-dimethoxycoumarin, 4-bromomethyl-7-acetoxycoumarin and 3
      bromomethyl-7-methoxy-1,4-benzoxazin-2-one. A synthetic alpha-branched carboxylic
      acid was derivatized with the same reagents and used as an internal standard
      along with the mycolic acids. The derivatized samples were analyzed by reversed
      phase HPLC on a Waters Novapak C18, 4 microns particle size, 150 mm x 3.9 mm
      stainless-steel column. Two solvent systems were used: (1) methanol and methylene
      chloride with the column at 30 degrees C, and (2) methanol and isopropanol with
      the column at 50 degrees C. Detection sensitivity with the fluorescent reagents
      was 16-50 times greater than the sensitivity observed with PBPB-derivatized
      samples. Unique mycolic acid elution profiles for the two mycobacterial species
      could be achieved with each of the solvent systems and derivatization reagents
      tested. Thus, the HPLC analysis of pre-column derivatized mycolic acids was
      useful as a means of rapidly identifying mycobacterial species. Replacement of
      methylene chloride with isopropanol and PBPB with a fluorescent derivatizing
      reagent could increase the safety and sensitivity of the assay, and make it more
      useful for the clinical identification of mycobacterial infections.

PMID- 7719453
TI  - Simultaneous determination of granisetron and its 7-hydroxy metabolite in human
      plasma by reversed-phase high-performance liquid chromatography utilizing
      fluorescence and electrochemical detection.
AB  - A highly sensitive and selective high-performance liquid chromatographic method
      was developed for the determination of granisetron and its active metabolite, 7
      hydroxygranisetron (7OH-G) in human plasma. Granisetron is a selective 5
      hydroxytryptamine receptor antagonist used in the treatment of cytotoxic drug
      induced emesis. The method involves isolation of granisetron, 7OH-G and the
      internal standards from plasma by solid-phase extraction prior to reversed-phase
      ion-pair chromatographic separation on an octyl silica column with subsequent
      quantification of analytes simultaneously either with electrochemical (7OH-G) or
      fluorescence (granisetron) detectors which are placed in series. The recovery of
      granisetron and 7OH-G from human plasma was quantitative. Using 1 ml of plasma,
      the limits of quantification for granisetron and 7OH-G were 0.1 and 0.25 ng/ml,
      respectively. Linear responses in analyte/internal standard peak-area ratios were
      observed for analyte concentrations ranging from 0.1 to 50 ng/ml plasma.
      Precision and accuracy were within 13% across the calibration range for both
      granisetron and 7OH-G. The method was sufficiently sensitive, accurate and
      precise to support pharmacokinetic studies for granisetron and 7OH-G, in both
      normal and patient populations.

PMID- 7719454
TI  - Extending the scope of chiral separation of basic compounds by cyclodextrin
      mediated capillary zone electrophoresis.
AB  - In a previous paper on cyclodextrin-mediated capillary zone electrophoresis, it
      was shown that the use of short-chain tetraalkylammonium cations leads to a
      reversal in the direction of the electroosmotic flow without an adverse effect on
      enantioselectivity. As a result, enantiomeric resolution of basic (cationic)
      compounds can be improved as the electroosmotic flow counteracts the migration of
      solute enantiomers. It is demonstrated in this report that the scope of chiral
      separation of basic compounds can be further extended by a combination of
      reversing the electroosmotic flow and enhancing enantioselectivity through the
      chemical modifications of beta-cyclodextrin. Therefore, beta-cyclodextrin and its
      derivatives were evaluated as chiral recognition agents for the chiral
      separations of 22 basic compounds with rather complex molecular structures. The
      differences in enantioselectivity displayed by beta-cyclodextrin and derivatives
      are discussed in order to achieve a better understanding of the chiral
      interactions involved in the discrimination of solute enantiomers.

PMID- 7719455
TI  - Mass spectrometric detectors for samples separated by planar electrophoresis.
AB  - Mass spectrometric detection for samples separated by planar chromatography (high
      performance thin-layer chromatography and planar electrophoresis) has evolved
      over the past 10 years from concept to feasibility and to commercial
      availability. This review concentrates on the interface between planar
      electrophoresis and mass spectrometry. Although hardware aspects of the interface
      have been developed and refined over the past few years, and there are impressive
      demonstrations of feasibility, we are only beginning to exploit new methods in
      sample storage, preparation and reaction in conjunction with planar
      chromatographic separation, and new uses of complex multi-dimensional imaging
      data.

PMID- 7719456
TI  - Selectivity control in micellar electrokinetic chromatography of small peptides
      using mixed fluorocarbon-hydrocarbon anionic surfactants.
AB  - Electrophoretic mobilities and capacity factors for a group of Trp-containing
      small peptides were determined by micellar electrokinetic chromatography (MEKC)
      using mixtures of a fluorocarbon anionic surfactant, lithium perfluorooctane
      sulfonate, and a hydrocarbon anionic surfactant, lithium dodecyl sulfate. Upon
      mixing these two surfactants, which have different microenvironments and
      interactive characteristics, greater control over migration of solutes is
      achieved. The changes in the composition of mixed micelles such as the mole
      fraction of the surfactants result in different solute-micelle binding as well as
      migration times of the micelles (tmc). Consequently, capacity factor, selectivity
      and elution window (tmc/t0) change with the composition of the mixed micellar
      system. Another characteristic of the mixtures of fluorocarbon-hydrocarbon
      surfactants is the possibility of forming two different types of micelles which
      offers an additional partitioning process for each solute in the MEKC system.
      Such a unique phenomenon offers a higher degree of selectivity control. This
      mixed MEKC system is quite effective for the separation of small peptides. It
      provides an alternative to the free-solution capillary zone electrophoresis
      system for the separation of charged solutes with nearly identical
      electrophoretic mobility.

PMID- 7719457
TI  - Linear solvation energy relationships in micellar liquid chromatography and
      micellar electrokinetic capillary chromatography.
AB  - Linear solvation energy relationships (LSERs) were used to evaluate and
      characterize chemical interactions that influence retention behavior in micellar
      liquid chromatography (MLC) and micellar electrokinetic capillary chromatography
      (MEKC). High correlations were found between solutes' capacity factors in MLC and
      in MEKC, as well as binding constants to micelles and their solvatochromic
      parameters using two anionic surfactants, sodium dodecyl sulfate (SDS) and sodium
      cholate (SC), and one cationic surfactant, tetradecyltrimethylammonium bromide
      (C14TAB). Surprisingly, in the C14TAB MLC system capacity factor (k') vs.
      solvatochromic parameters gives better correlation than log k' vs. solvatochromic
      parameters, which is an opposite behavior to that observed in the SDS MLC system.
      The capacity factors in the C14TAB MLC system were characterized using LSERs with
      and without organic modifiers. It was found that the addition of a small amount
      of short-chain alcohols (e.g., 7% 2-propanol or 5% butanol) does not
      significantly change the high correlations between k' vs. solvatochromic
      parameters. The changes in the coefficients with the volume fraction of organic
      solvents were explained by comparing the differences in chemical natures between
      mobile phase and stationary phase. Stationary phase shows a significant effect on
      the chemical interactions in MLC through LSER study using a diphenyl column and a
      C8 column. LSERs were also used to characterize retention behavior in MEKC. High
      correlations between the logarithm of solutes' capacity factors and their
      solvatochromic parameters were observed for a group of 25 uncharged substituted
      aromatic compounds and polycyclic aromatic hydrocarbons with SDS and SC micelles.
      It was found that solutes' size and basicity are the two dominant factors that
      influence the migration behavior in MEKC.

PMID- 7719458
TI  - Micellar liquid chromatographic separation of sulfonamides in physiological
      samples using direct on-column injection.
AB  - A mixture of twelve sulfonamides was separated by micellar liquid chromatography
      (MLC) using sodium dodecyl sulfate (SDS) micelles and a hydrophilic endcapped C18
      column. Retention behavior and selectivity pattern of sulfonamides in MLC were
      examined with the change of SDS concentration and volume fraction of an organic
      modifier (1-propanol). The suitable condition was found to be 0.070 M SDS and
      6.0% 1-propanol for the separation of these twelve sulfonamides. Under this
      condition, the isocratic separation of the sulfonamides was achieved within 15
      min with a relatively high column efficiency for MLC (ca. 7000 plates/25 cm
      column). Retention times of these twelve sulfonamides were found to be very
      repeatable, which is due to the highly reproducible retention behavior in MLC.
      The same twelve sulfonamides were successfully separated in the spiked
      physiological fluids (human urine and cow milk) through direct on-column
      injection by MLC.

PMID- 7719459
TI  - Liquid chromatographic determination of the mycotoxin fumonisin B2 in
      physiological samples.
AB  - The fungus Fusarium moniliforme produces a group of mycotoxins, the fumonisins,
      of which the most abundant are fumonisins B1 (FB1) and B2 (FB2). Previously
      developed analytical methods for the determination of FB1 in physiological
      samples have been modified for the determination of FB2 by the use of less polar
      extraction solvents. Plasma and urine extracts were purified on strong anion
      exchange solid-phase extraction cartridges and fecal extracts on reversed-phase
      (C18) cartridges. FB2 in purified extracts was determined by reversed-phase HPLC
      with fluorescence detection using performed o-phthaldialdehyde derivatives. These
      methods were reproducible (R.S.D. of less than 6%) with recoveries greater than
      85%. In a short preliminary study, they have been applied to the determination of
      the fate of FB2 dosed to rats by gavage. Of the dose given to the animals, over
      90% was recovered unmetabolised in the feces within 48 h.

PMID- 7719460
TI  - Determination of L-735 524, an human immunodeficiency virus protease inhibitor,
      in human plasma and urine via high-performance liquid chromatography with column
      switching.
AB  - A method for the determination of an HIV protease inhibitor, L-735 524, in human
      plasma and urine is described. Isolation of the analyte and the internal standard
      from the matrices was achieved via multiple liquid-liquid extractions with methyl
      tert.-butyl ether. The analyte lacks significant UV absorption at wavelengths
      greater than 220 nm, hence a column switching system using a cyano and C18 column
      was used to further purify the extracts prior to UV detection at 210 nm. The
      assay has been found to be linear and has been validated over the concentration
      range of 5 to 500 ng/ml, when 1-ml aliquots of plasma or urine were extracted.
      The assay has been utilized to support human pharmacokinetic studies.

PMID- 7719461
TI  - Alkylsulphonic acid ion pairing with radial compression columns for determining
      plasma or cerebrospinal fluid 1-beta-D-arabinofuranosylcytosine in pediatric
      pharmacokinetic analysis.
AB  - In order to accurately and precisely measure plasma and cerebrospinal fluid (CSF)
      1-beta-D-arabinofuranosylcytosine (Ara-C) in pediatric samples with adequate
      sensitivity and without interference, we have developed a reversed-phase ion
      pairing technique utilizing the free amino group of the pyrimidine ring of Ara-C.
      Optimum resolution and separation was achieved utilizing a 4 microns C18 radial
      compression column. Ara-C and the internal standard 8-bromo-cyclic-AMP eluted at
      6.5 and 4.6 min, respectively, with complete resolution. The minimum detectable
      amount is 2.5 pmol in a 50-microliters volume. The assay was linear in both
      plasma and CSF. Intra- and inter-day assay precision were less than 4% and 9%,
      respectively, for plasma with similar results obtained for CSF. Neither
      endogenous compounds nor commonly co-administered drugs interfere. Validity for
      our method was supported by the successful assay of over 400 pediatric plasma and
      50 CSF samples for pharmacokinetic analysis. The method offers accuracy,
      precision, sensitivity and efficiency for plasma or CSF Ara-C determination.

PMID- 7719462
TI  - Rapid liquid chromatographic-mass spectrometric assay for oxymetazoline in whole
      rat blood.
AB  - A rapid HPLC-electrospray mass spectrometric assay for the quantitation of
      oxymetazoline in whole rat blood has been developed. Sample preparation was a
      single liquid-liquid extraction after addition of a deuterated internal standard
      (IS) and pH adjustment. An aliquot of reconstituted extract was injected onto a
      narrow-bore octadecyl reversed-phase column at a flow-rate of 400
      microliters/min. Using a 20:1 post-column split, 5% of the eluent was introduced
      into the mass spectrometer interface. Elution of the analyte and IS occurred in
      less than 2 min. This rapid separation was made possible because of the sample
      cleanup and the selectivity of the mass spectrometric detection. The [M+H]+ ions
      for oxymetazoline (m/z 261) and [2H9]oxymetazoline (m/z 270) were detected using
      selected ion monitoring. The linear range of the assay was 0.67-167 ng/g of blood
      and the limit of quantitation with a 0.30-g sample was 1.0 ng/g. The assay
      permitted the analysis of nine samples per hour with the requisite sensitivity
      and selectivity and was used to determine the blood pharmacokinetics of
      oxymetazoline in rats dosed via intravenous and intranasal routes.

PMID- 7719463
TI  - Unified enantioselective capillary chromatography on a Chirasil-DEX stationary
      phase. Advantages of column miniaturization.
AB  - Immobilized Chirasil-DEX (mono-6-O-octamethylenepermethyl-beta-cyclodextrin
      chemically linked to dimethylpolysiloxane) can be employed as a versatile chiral
      stationary phase in chromatography. The chiral polymer has a long lifetime and is
      configurationally and thermally stable. The concept of unified enantioselective
      chromatography has been demonstrated for the enantiomer separation of
      hexobarbital by gas chromatography, supercritical fluid chromatography, liquid
      chromatography and capillary electrochromatography on a single open-tubular
      column (1 m x 50 microns I.D.) coated with Chirasil-DEX. The advantages of
      miniaturization in contemporary chromatographic enantiomer separation are
      demonstrated. Chirasil-DEX coated on porous silica is also useful for enantiomer
      separation in high-performance liquid chromatography.

PMID- 7719464
TI  - Stereoselective pharmacokinetics of dihydropyridine calcium antagonists.
AB  - Many dihydropyridine calcium antagonists are widely used for the treatment of
      angina and hypertension, and many more are under development. Most of these drugs
      have one or more chiral centre, and the pharmacological activity between the
      enantiomers for these drugs is known to be markedly different. First, the
      stereospecific assay methods for these drugs in plasma or serum are reviewed with
      emphasis on chiral stationary phase high-performance liquid chromatography for
      their determination. Next, the stereoselective pharmacokinetics of these drugs
      (nilvadipine, nitrendipine, felodipine, nimodipine, manidipine, benidipine and
      nisoldipine) in animals, healthy subjects and patients with hepatic disease is
      reviewed. Enantiomer-enantiomer interaction, enantiomeric inversion and the
      stereochemical aspects of pharmacokinetic drug interactions in these drugs are
      also described.

PMID- 7719465
TI  - Diastereomeric beta-lactam antibiotics. Analytical methods, isomerization and
      stereoselective pharmacokinetics.
AB  - Stereospecific HPLC methods for the determination of various diastereomeric beta
      lactam antibiotics are reviewed. Stereoselectivity in the absorption,
      distribution and excretion of several diastereomeric beta-lactams is summarized.
      The isomerization of beta-lactam isomers and its influence on the
      pharmacokinetics and pharmacodynamics are discussed.

PMID- 7719466
TI  - Direct determination of E2020 enantiomers in plasma by liquid chromatography-mass
      spectrometry and column-switching techniques.
AB  - High-performance liquid chromatography with column switching and mass
      spectrometry (MS) was applied to the on-line determination and resolution of the
      enantiomers of E2020 (acetylcholinesterase inhibitor) in plasma. This system
      employs two avidin columns and fast atom bombardment (FAB)-MS. A plasma sample
      was injected directly into an avidin trapping column (10 mm x 4.0 mm I.D.). The
      plasma protein was washed out from the trapping column immediately while E2020
      was retained. After the column-switching procedure, E2020 was separated
      enantioselectivity in an avidin analytical column. The separated E2020
      enantiomers were specifically detected by FAB-MS without interference from
      metabolites of E2020 and plasma constituents. The limit of quantification for
      each enantiomer of E2020 in plasma was 1.0 ng/ml and the intra- and inter-assay
      relative standard deviations for the method were less than 5.2%. The assay was
      validated for enantioselective pharmacokinetic studies in the dog.

PMID- 7719467
TI  - Investigation of the stereoselective metabolism of the chiral H1-antihistaminic
      drug terfenadine by high-performance liquid chromatography.
AB  - The enantiomers of the racemic H1-antihistaminic drug terfenadine (1) have been
      resolved by fractional crystallization of the diastereomeric salts with optically
      active 2-chlorotartranilic acid. The enantiomeric excess of both terfenadine
      enantiomers was determined using an achiral and a chiral HPLC system after
      formation of diastereomers with S-(+)-naphthylethylisocyanate. To investigate the
      metabolism of terfenadine after oral administration, an achiral HPLC system,
      equipped with a conventional reversed-phase column, was used to quantify the main
      metabolite MDL 16.455 (2) in human serum and urine. The determination of the
      enantiomeric composition of 2 was achieved using an Ultron ES-OVM column as
      chiral stationary phase. Metabolite 2, extracted from human blood plasma, was
      found to be enriched in the R-enantiomer, but was excreted in urine as racemate.
      The results of a study including six volunteers are presented.

PMID- 7719468
TI  - Ability of non-cyclic oligosaccharides to form molecular complexes and its use
      for chiral separation by capillary zone electrophoresis.
AB  - The binding constants (K) for complexation of the phenyl acetates with linear
      alpha-1,4-linked dextrins have been determined from the kinetics of the
      hydrolyses of the esters. The K value tends to increase with increasing the
      number of the glucopyranose units, suggesting hydrophobic interaction as a
      binding force. The weak ability of the linear dextrins to form the molecular
      complexes makes it possible to separate the enantiomers of binaphthyl derivatives
      such as 1,1'-binaphthyl-2,2'-dicarboxylic acid, 1,1'-binaphthyl-2,2'-diyl
      hydrogenphosphate and 2,2'-dihydroxy-1,1'-binaphthyl-3,3'-dicarboxylic acid in
      their anionic forms. Hydrogen bonding as well as hydrophobic interaction is
      suggested as an essential force for enantioselective complexation between
      saccharide and anionic binaphthyl.

PMID- 7719469
TI  - Stereochemical determinants of the nature and consequences of drug metabolism.
AB  - Enantiomeric discrimination in drug disposition depends on the mechanism of the
      process under consideration. Absorption, distribution and excretion are generally
      passive processes which do not differentiate between enantiomers, but enzymic
      metabolism and protein binding, to plasma or tissue proteins, can show a high
      degree of stereoselectivity. In terms of metabolism, chiral discrimination occurs
      at both substrate and product levels, giving rise to five distinct stereochemical
      courses for drug metabolism, namely (i) prochiral-->chiral, (ii) chiral-->chiral,
      (iii) chiral-->diastereoisomer, (iv) chiral-->non-chiral and (v) chiral
      inversion. As a result, the metabolic and pharmacokinetic profiles of enantiomers
      after administration of racemic drugs can be very variable, so that the exposure
      to the two enantiomers may be very different. There now an enormous number of
      examples of each of these possibilities. The net result of the interaction of the
      stereoselectivities of these various processes can obscure the fact that one (or
      more) shows a marked stereoselectivity. This is particularly the case for
      metabolism: while the ratios of the total plasma clearance of the enantiomers of
      a wide range of drugs never exceed 2, individual metabolic pathways often show
      much greater stereoselectivity. This is particularly evident for those high
      affinity, low-capacity enzyme systems which exhibit genetic polymorphism, namely
      the human cytochromes P450 2C18 and 2D6. This review provides an introduction to
      the stereoselectivity of drug metabolism.

PMID- 7719470
TI  - Optimization of the separation of enantiomers of basic drugs. Retention
      mechanisms and dynamic modification of the chiral bonding properties on an alpha
      1-acid glycoprotein column.
AB  - The chromatographic properties of 29 basic drugs were studied by varying the pH
      and the concentration of inorganic ions in the mobile phase. It was observed that
      the chromatographic performance of most hydrophobic basic drug compounds could be
      strongly enhanced by decreasing the pH in the mobile phase from 7 to 4-6. The
      enantioselectivity increased and a much faster resolution was obtained. The
      results indicate that ion exchange and ion-pair distribution may be involved in
      the retention process of cationic drug enantiomers. Increasing the concentration
      of acetate and phosphate increases the retention of the enantiomers of the drug
      compounds. The relative contribution of the two retention processes can be
      affected by the pH and the nature and the concentration of the ions in the mobile
      phase. Decreasing the pH reduces the influence of the ion-exchange process since
      the negative charge of the protein is decreased. The enantioselectivity is also
      greatly affected by increasing salt concentration.

PMID- 7719471
TI  - Enantioselectivity of bovine serum albumin-bonded columns produced with isolated
      protein fragments.
AB  - The enantioselectivity of bovine serum albumin (BSA)-bonded columns produced with
      isolated protein fragments was investigated. The BSA fragment BSA-FG75 was
      isolated by size-exclusion chromatography followed by peptic digestion of BSA.
      The isolated BSA-FG75 was a mixture of three peptides, and was mainly an N
      terminal half peptide(s) with an average molecular mass of about 35,000. The BSA
      and BSA-FG75 proteins were bound to aminopropylsilica gels activated by N,N'
      disuccinimidyl carbonate. The amounts of the proteins bound were about 2 and 5.5
      mumol/g for the BSA and BSA-FG75, respectively. Chiral recognition of 2
      arylpropionic acid derivatives, benzodiazepines, warfarin and benzoin was
      obtained with the BSA-FG75-bonded columns, but no chiral recognition of
      tryptophan or kynurenine was obtained. The intact BSA column gave a higher
      enantioselectivity than the BSA-FG75 column for most of the compounds tested,
      whereas the BSA-FG75 column gave a higher enantioselectivity than the intact BSA
      column for lorazepam and benzoin, and had a higher capacity for benzoin. These
      results are due to a higher density of chiral recognition site(s) on the BSA-FG75
      column. Also, the BSA-FG75 column was as stable as the intact BSA column for a
      continuous flow of eluent.

PMID- 7719472
TI  - Study of the enantioselective binding between BOF-4272 and serum albumins by
      means of high-performance frontal analysis.
AB  - High-performance frontal analysis (HPFA) was incorporated in an on-line HPLC
      system for the study of the enantioselective binding of BOF-4272, a new xanthine
      oxidase inhibitor, with human, bovine and rat serum albumins. This HPLC system
      consists of a HPFA column (diol-silica column), an extraction column (C4 column)
      and a chiral separation column (beta-cyclodextrin immobilized silica column),
      which were connected in series via two column switching valves. After the direct
      injection of a solution of 0.5-400 microM racemic BOF-4272 and 550 microM serum
      albumin onto the HPFA column, BOF-4272 was eluted, under a mild mobile phase
      condition (phosphate buffer, pH 7.4, ionic strength 0.17), as a zonal peak
      containing a plateau region. The drug concentration in the plateau region is the
      same as that for the unbound drug concentration in the sample solution. A given
      volume of this plateau region was transferred into the extraction column, and
      subsequently the extracted BOF-4272 was transferred into the chiral separation
      column to determine the unbound concentration of each enantiomer. The binding
      between BOF-4272 and the serum albumins was enantioselective and species
      dependent. The unbound concentration of the (+)-isomer in rat serum albumin
      solution was 1.04-1.14 times larger than that of the antipode, while the unbound
      concentration of the (-)-isomer in bovine serum albumin solution was 1.04-1.16
      times larger than that of the antipode. The enantioselectivity of the binding
      between BOF-4272 and human serum albumin was concentration dependent.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7719473
TI  - Manufacture of recombinant proteins with safe and validated chromatographic
      sorbents.
AB  - Purification of recombinant proteins to achieve homogeneity, purity, consistency
      and potency as required for therapeutic proteins and in vivo diagnostics is
      performed under stringent and validated conditions. As liquid chromatography is
      one of the major technologies used for this purpose, it has to be carried out
      according to special regulatory guidelines. One of the reported aspects is the
      long-term consistency of a chromatographic process and validation of its
      operation; other aspects described are more sorbent oriented. In-place cleaning
      and sterilization are also very important aspects, the efficiency of which is
      dependent on the chosen working conditions and the chemical nature of the
      sorbents. Drastic cleaning may deteriorate the chromatographic matrices,
      releasing chemicals that may contaminate the biologicals of interest, which
      modifying the behaviour of the chromatographic columns. Moreover, leachable
      compounds, when present, could have adverse effects in case of high toxicity.
      Determination of leaching levels and toxicity tests are part of the validation
      steps to turn chromatographic separations into consistent, effective and safe
      production processes for biologicals.

PMID- 7719474
TI  - Purification of factor VIII and von Willebrand factor from human plasma by anion
      exchange chromatography.
AB  - Factor VIII (anti-hemophilia A factor) is isolated from human plasma.
      Purification is carried out by a combination of precipitation and chromatographic
      procedures. After precipitation, the first step in virus inactivation is achieved
      through the effect of a non-ionic detergent such as Tween 80, and a solvent, e.g.
      tri-n-butylphosphate (TnBP). By subsequent anion-exchange chromatography, a
      highly enriched product is isolated, consisting of a complex formed by factor
      VIII and von Willebrand factor (FVIII-vWF). This treatment also removes the virus
      inactivating reagents to quantities in the low ppm range. The second step in
      virus inactivation is aimed specifically at the non-enveloped viruses and
      consists of pasteurization at temperatures higher than 60 degrees C for 10 h.
      Through the addition of stabilizers, between 80% and 90% of the initial activity
      of FVIII is preserved during the modified pasteurisation. Along with the possibly
      denatured proteins the stabilizers, such as sugars, amino acids and bivalent
      cations, are subsequently removed by ion-exchange chromatography. The two-fold
      virus inactivation, by solvent/detergent treatment and subsequent pasteurisation,
      allows the destruction of both lipid-enveloped and non-enveloped viruses. During
      the procedure FVIII is stabilized through the high content of vWF. The complex
      consisting of FVIII and vWF can be dissociated by adding calcium ions.
      Subsequently both glycoproteins from this complex are separated from one another
      by further anion-exchange chromatography.

PMID- 7719475
TI  - Affinity purification of a mannose-binding protein, a sensitive tool in the
      diagnostics of IgM, via site-directed phosphorylated mannan bound to alumina.
AB  - Ca2+ -dependent mannose-binding proteins (MBPs) belong to the family of animal
      lectins. They perform in vivo as defence molecules that act as opsonins by
      enhancing the clearance of mannose rich pathogens and have been used in vitro for
      the purification of IgM. MBPs have been previously isolated by methods based on
      binding the protein moiety of various mannan species to different matrices.
      However, the mannan-protein complexes did not have a constant protein content and
      the yield of the isolated MBPs was variable. In the present study we describe a
      new approach for the affinity purification of MBPs based on the main
      polysaccharide moiety of the complex. After removal of residual phosphate groups
      naturally occurring at the C-3 position of the sugar, which interfere with MBP
      recognition, the mannan was phosphorylated enzymatically at C-6, at which
      position the OH group is not required for lectin binding. The enzymatically
      phosphorylated mannan bound to an alumina column was used successfully for MBP
      separation from rabbit serum. The mannose-binding protein obtained was used in
      our study for diagnostic purposes in the identification and determination of very
      low concentrations of IgM.

PMID- 7719476
TI  - Recombinant soluble Fc gamma receptors: production, purification and biological
      activities.
AB  - Soluble forms of low affinity receptors for the Fc portion of IgG circulate in
      body fluids and regulate immune functions. We describe the transfection,
      production and purification techniques which allow the preparation, at a
      laboratory scale, of milligram amounts of glycosylated recombinant mouse and
      human soluble Fc gamma receptors. These recombinant products bind IgG and are
      biologically active on immune responses, like their normal counterparts.

PMID- 7719477
TI  - Rapid high-performance liquid chromatographic quantification of recombinant human
      antithrombin III during production and purification.
AB  - For monitoring of recombinant human antithrombin III during cell culture
      processes and subsequent purification steps a rapid method for quantitative
      determination was developed. The need for the introduction of this rapid method
      came from the limited availability of a quantitative enzyme-linked immunosorbent
      assay (ELISA) and the very time-consuming ELISA procedure. The developed method
      is based on reversed-phase high-performance liquid chromatography using a C4
      column. The separation by gradient elution using water and acetonitrile takes
      less than 20 min even when complex samples, such as serum containing cell culture
      samples, have to be analyzed. Automation and a high sample throughput are
      possible with this reliable method. If necessary, insulin, transferrin and
      albumin can also be quantified with minor changes of the elution profile.

PMID- 7719478
TI  - Application of high-performance membrane chromatography for separation of
      annexins from the plasma membranes of liver and isolation of monospecific
      polyclonal antibodies.
AB  - The separation of annexins, calcium-binding plasma membrane-associated proteins
      from rat liver and Morris hepatoma 7777 by high-performance membrane
      chromatography (HPMC) is described. The annexins with low molecular masses, CBP
      33 and CBP 35, and the annexin with a high molecular mass, CBP 65/67, can be
      separated within 10 min from one another by anion-exchange HPMC under non
      denaturing conditions. The separation devices used consist of compact, porous
      disks (QuickDisk) on the one hand and of bundled membranes made of cellulose
      fibers (MemSep) on the other. Both have been found to be equally well suited for
      this separation. The annexins obtained in this way are subsequently bound to
      epoxy-activated porons disks and used for the separation of monospecific
      polyclonal antibodies against the annexin CBP 65/67.

PMID- 7719479
TI  - Resolution of isoforms of natural and recombinant fibrolase, the fibrinolytic
      enzyme from Agkistrodon contortrix contortrix snake venom, and comparison of
      their EDTA sensitivities.
AB  - Fibrolase, the fibrinolytic enzyme from Agkistrodon contortrix contortrix snake
      venom, is a zinc metalloproteinase with a molecular mass of 23 kDa. We report a
      method to isolate two isoforms of natural fibrolase (fib1 and fib2) and three
      isoforms of recombinant fibrolase (r-fib1, r-fib2 and r-fib3) using CM 300 cation
      exchange high-performance liquid chromatography. Utilizing mass spectrometry we
      characterized differences in molecular masses of the isoforms of r-fibrolase.
      These findings suggest that the isoforms differ by minor sequence variations at
      their amino-termini. Since the stability of fibrolase is exquisitely sensitive to
      the removal of zinc, we examined the EDTA sensitivity of the isoforms of
      fibrolase and r-fibrolase to determine if their different chromatographic
      behavior is related to differences in their zinc affinities. All of the isoforms
      examined appear to have similar zinc binding affinities. Thus, the IC50
      (concentration of EDTA to produce 50% inhibition of enzymatic activity) for fib1
      is 160 microM. For the closely related r-fib1, the IC50 is 180 microM. Similarly,
      r-fib3 has an IC50 of 140 microM.

PMID- 7719480
TI  - Primary structure control of recombinant proteins using high-performance liquid
      chromatography, mass spectrometry and microsequencing.
AB  - The conformity of two recombinant proteins (a von Willbrand factor fragment and
      human serum albumin, consisting of respectively 289 and 585 amino acids) has been
      examined by HPLC combined with mass spectrometry and microsequencing, on both
      intact material and fragment peptides obtained by proteolytic cleavage. These
      studies confirmed that the primary structure of the recombinant proteins
      corresponds to that predicted from their gene, particularly the integrity of
      their N and C termini, and, in the case of albumin, the agreement between the
      observed disulfide bond pattern and the published model. Furthermore, the
      structure of an albumin-related compound could be elucidated. Application of LC
      MS for batch-to-batch quality control is also under discussion.

PMID- 7719481
TI  - Deamidation of asparagine and glutamine residues in proteins and peptides:
      structural determinants and analytical methodology.
AB  - Non-enzymatic deamidation of asparagine and glutamine residues in proteins and
      peptides are reviewed by first outlining the well-described reaction mechanism
      involving cyclic imide intermediates, followed by a discussion of structural
      features which influence the reaction rate. The second and major part describes
      analytical techniques that allow studying deamidation in proteins using
      recombinant human growth hormone and recombinant hirudin as examples. Finally,
      the significance of non-enzymatic deamidation with respect to the production of
      pharmaceutical proteins is discussed.

PMID- 7719482
TI  - Analysis of the primary structure and post-translational modifications of the
      Schistosoma mansoni antigen Smp28 by electrospray mass spectrometry.
AB  - The Schistosoma mansoni glutathione-S-transferase with an apparent molecular mass
      of 28 kDa, Smp28, has a blocked N-terminus which has been elucidated with the aid
      of the cDNA sequence combined with mass spectrometry and amino acid composition
      analysis of the N-terminal tryptic peptide. The blocked N-terminal tryptic
      peptide (m/z 695.8) contained an equimolar ratio of E, G, H, A, I and K3 upon
      amino acid composition analysis in agreement with its expected sequence AGEHIK,
      and showed a delta m = +41.7 Da compared to the predicted mass, which is
      consistent with the N-terminal alanine being acetylated (delta m = +42.0 Da). The
      mass of the complete molecule (23,744.5 +/- 3.3 Da) determined by electrospray
      mass spectrometry showed a further mass increase of 14 Da with respect to Smp28
      containing an N-acetylated alanine. This result is consistent with one of the
      seven methionines being present as a methionine sulfoxide in ca. 90% of the Smp28
      molecules in this preparation. Tryptic mapping of Smp28 showed five of the seven
      methionines to be partially oxidized by mass spectrometry. This is indicative of
      the ease with which this modification occurs. Two minor components were detected
      along with the intact molecule, corresponding to modified forms of the molecule,
      originating from reaction of the only cysteine residue either with itself forming
      a covalent dimer or with glutathione. On-line liquid chromatography-mass
      spectrometry has been compared with the off-line complete tryptic map of Smp28
      confirming 97% of the primary structure in less than 2 h.

PMID- 7719483
TI  - Sodium dodecyl sulfate polyacrylamide gel- and replaceable polymer-filled
      capillary electrophoresis for molecular mass determination of proteins of
      pharmaceutical interest.
AB  - Performance of commercially available replaceable SDS polymer-filled capillary
      electrophoresis (rPGCE) systems were evaluated for the determination of the
      molecular mass of proteins of pharmaceutical interest. The mass values obtained
      by these systems were compared with those obtained by SDS-PAGE and high
      performance size exclusion chromatographic (HPSEC). The molecular masses of
      proteins determined by rPGCE were not significantly different and agreed closely
      with those obtained by SDS-PAGE and with the theoretical values of the proteins.
      HPSEC gave the least reliable data. Performance of the SDS crosslinked
      polyacrylamide gel-filled capillary electrophoresis system was superior to that
      of the commercially available rPGCE systems. Nevertheless, the rPGCE systems
      present significant advantages over the conventional SDS-PAGE and HPSEC methods
      for rapid analysis and improved precision for the determination of the molecular
      masses of proteins of pharmaceutical interest.

PMID- 7719484
TI  - Interaction of cyclosporin A and two cyclosporin analogs with cyclophilin:
      relationship between structure and binding.
AB  - The immunosuppressant drug cyclosporin A exists as various conformers in water.
      Up to 1 h is needed to reach maximum complex formation after mixing the drug with
      its receptor, cyclophilin, or an antibody, indicating that only a fraction of the
      conformers in aqueous solution adopts a conformation suitable for binding. In the
      present study we compare the binding behavior of cyclosporin to that of two
      analogs, using a biosensor instrument (BIAcore, Pharmacia). The amount of complex
      formation was measured as a function of time after adding the peptides to
      cyclophilin. The equilibrium affinity constants of cyclophilin for these analogs
      have been measured. The slow binding of cyclosporin to cyclophilin compared to
      the instant binding of the cyclosporin analogs supports the hypothesis that
      cyclophilin recognizes a well defined conformation of cyclosporin that exists in
      water prior to binding.

PMID- 7719485
TI  - Immunoaffinity measurement of recombinant granulocyte colony stimulating factor
      in patients with chemotherapy-induced neutropenia.
AB  - A high-performance immunoaffinity chromatographic technique has been developed
      for the measurement of recombinant human granulocyte colony stimulating factor in
      human patients receiving this agent, following neutropenia, arising from cancer
      chemotherapy. The technique employs a short, biocompatible polymer column packed
      with minute, antibody-coated glass beads. This system was applied to the analysis
      of recombinant human granulocyte colony stimulating factor in three different
      human body fluids. A reasonable degree of correlation was achieved when comparing
      the immunoaffinity technique to a conventional immunoassay, although the
      immunoaffinity technique displayed greater specificity.

PMID- 7719486
TI  - Delivery of interleukin 2 for immunotherapy.
AB  - The local production of interleukin 2 (IL-2) by T lymphocytes acts to enhance the
      immune response by inducing growth and differentiation of a variety of immune
      cells. In clinical situations that require immunostimulation, such as vaccination
      and enhancement of tumor immunity, IL-2 therapy has been considered; however, the
      extraordinary toxicity of the drug inoculated systemically has greatly limited
      its application. Since the most serious toxic consequences of the drug are
      related to its systemic delivery, alternative strategies have been developed.
      Local delivery of the cytokine has been successfully used in some circumstances,
      and this form of delivery does not result in the life-threatening complications
      that limit systemic use. Liposome encapsulated IL-2 represents a mechanism to
      accentuate local delivery by causing a depot effect. Finally, the use of IL-2 has
      been predicated on the conception of the cytokine as an absolute monomer.
      Nevertheless, IL-2 spontaneously forms noncovalent and covalent self
      associations. Because covalent dimers have been shown to initiate differential
      signalling in target cells, it is necessary to account for this property in
      devising and evaluating therapeutic protocols; moreover, it seems possible to use
      this property for modifying and regulating the therapeutic response.

PMID- 7719487
TI  - Application of capillary high-performance liquid chromatography to biotechnology,
      with reference to the analysis of recombinant DNA-derived human growth hormone.
AB  - Using capillary HPLC, femtomole amounts of recombinant DNA-derived human growth
      hormone (rhGH) have been successfully detected from solutions at nanomolar
      concentrations. The separation used capillaries of 15 cm x 320 microns I.D. and
      detection was with a UV absorbance detector containing a capillary Z-shaped flow
      cell. A sample of rhGH that was recovered from rat serum was analyzed by
      capillary reversed-phase HPLC, using both acidic- and neutral-pH mobile phases,
      as well as by capillary ion-exchange chromatography. When compared to HPLC
      separations performed at flow-rates of 1 ml/min, the sensitivity of the detection
      was increased 200 times, without any loss in resolution. Sub-microgram amounts of
      rhGH were also analyzed by tryptic mapping using capillary HPLC and peptides were
      identified by capillary LC-MS.

PMID- 7719488
TI  - Quantitative analysis of phosphorothioate oligonucleotides in biological fluids
      using direct injection fast anion-exchange chromatography and capillary gel
      electrophoresis.
AB  - The analysis of antisense phosphorothioate DNA (SODN) in human plasma via direct
      injection using anion-exchange high-performance liquid chromatography (AE-HPLC)
      is presented. The method relies on the ability to selectively extract
      phosphorothioate DNA from undigested serum, plasma and urine on anion-exchange
      resins. The automated HPLC method can analyze a sample every 5 min with a limit
      of detection of 50 ng/ml (ppb). The DNA was collected, desalted and analyzed by
      capillary gel electrophoresis. Due to the high resolving power of this technique,
      a qualitative assessment of enzymatic degradation of the antisense
      oligonucleotide can be made.

PMID- 7719489
TI  - Rapid purification of immunoglobulin G using aza-arenophilic chromatography:
      novel mode of protein-solid phase interactions.
AB  - A derivative of aza-arenophilic gel having a dichlorosubstituent and an hydroxy
      ion as a capping nucleophile has been prepared. The properties of this gel in
      relation to IgG purification have been investigated in details. In the presence
      of high salt (1.5 M), albumin and some other serum proteins did not bind to the
      gel. IgG and some other minor proteins, however, were bound to the gel. The bound
      proteins can be eluted with an acidic buffer. SDS-PAGE showed that the fraction
      eluted with 0.1 M sodium acetate pH 4.2 consisted mainly of IgGs.

PMID- 7719490
TI  - Recombinant human insulin. VI. Determination of recombinant human proinsulin by
      capillary zone electrophoresis: optimization of efficiency and selectivity.
AB  - The optimization of the separation of recombinant human insulin (rhI) and
      recombinant human proinsulin (rhP) by free-solution capillary zone
      electrophoresis in uncoated fused-silica capillaries with ionic and zwitterionic
      buffers was carried out. The relationship between the selectivity and pH of the
      buffer was established. The effects of pH and ionic strength of the buffer on
      protein adsorption on the capillary walls and Taylor diffusion was investigated.
      The separation of rhI and rhP with an efficiency of 200,000 theoretical plates
      was achieved using 20 mM Na2HPO4-NaOH buffer (pH 11.2). The proposed method
      allows the simultaneously determination of rhP and some rhI degradation products
      (which are also included in pharmacopoeias) in pharmacopoeially limited amounts
      in rhI.

PMID- 7719492
TI  - Nurse entrepreneurs.

PMID- 7719491
TI  - Recombinant human insulin. V. Optimization of the reversed-phase high-performance
      liquid chromatographic separation.
AB  - The applicability of reversed-phase high-performance liquid chromatography (HPLC)
      to the analysis of the products of recombinant insulin was studied. The influence
      of several mobile phases in reversed-phase and ion-pair HPLC on selectivity,
      resolution and sensitivity was investigated. Optimum conditions for the
      separation of insulin-related proteins on commercial and laboratory-made supports
      were established by means of three-dimensional optimizations of selectivity and
      resolution as a function of pH and ionic strength (mu). A mechanism for the
      separation of proteins with a mobile phase containing a high salt concentration
      and a pH near the isoelectric point of proteins is proposed. The questions of
      scaling up are considered. The proposed techniques allow the analysis of the main
      impurities and ensures a high quality of active insulin production.

PMID- 7719493
TI  - The battle against ignorance.

PMID- 7719494
TI  - Management perspectives. A nursing supervisor finding a way to handle chronic
      complainers.

PMID- 7719495
TI  - Tapping into community resources to confront the AIDS challenge.

PMID- 7719496
TI  - Inova's HIV clinical training/mentor program.

PMID- 7719497
TI  - Evaluating the severity of mitral stenosis.

PMID- 7719498
TI  - Nomogram for Doppler echocardiographic assessment of mitral stenosis in atrial
      fibrillation.
AB  - Non-invasive assessment of the stenotic mitral valve area is often difficult when
      the mitral stenosis is associated with atrial fibrillation. In this study, 16
      patients with mitral stenosis and atrial fibrillation were evaluated by
      transthoracic Doppler echocardiography. The mitral valve area calculated by the
      pressure half-time method was 1.65 +/- 0.73 cm2. The enddiastolic mitral gradient
      was obtained from the enddiastolic forward mitral flow velocity by application of
      the simplified Bernoulli equation. For each patient there was a linear
      relationship between the enddiastolic mitral gradient and the corresponding RR
      interval. The slope and intercept of this relationship were significantly
      correlated with the mitral valve area. From the regression equations describing
      these correlations we established a nomogram ascertaining mitral valve area from
      enddiastolic mitral gradient and corresponding heart rate. This nomogram was
      helpful in the non-invasive assessment of stenotic mitral valve area in the
      presence of atrial fibrillation.

PMID- 7719499
TI  - Increase in peak oxygen uptake by restoration of atrial contraction in patients
      after percutaneous transvenous mitral commissurotomy.
AB  - The aim of the present study was to determine the effect of sinus conversion
      after mitral commissurotomy on the exercise performance of patients with mitral
      stenosis (MS) and atrial fibrillation (Af). Electric cardioversion was attempted
      10 days after successful balloon mitral commissurotomy in 32 patients with MS and
      Af. Both symptom-limited exercise tests with respiratory gas analysis and
      constant workload exercise tests with echo-Doppler examinations were performed
      before, five days and three months after mitral commissurotomy, and five days
      after successful sinus conversion. The balloon commissurotomy attenuated the
      increase in transmitral pressure gradient during exercise. However, no
      significant increase either in peak oxygen uptake (PVO2) or stroke volume were
      observed even three months after commissurotomy in patients with persistent Af.
      Sinus conversion was successful in 17 patients and PVO2 increased from 21.4 +/-
      4.1 to 23.4 +/- 4.0 ml/min/kg (p < 0.01). The extent of the increase in PVO2 was
      related to the atrial contribution in transmitral flow (R2 = 0.39, y = 0.81x +
      1.2). Sinus rhythm was maintained for three months in 14 of 17 patients.
      Increased PVO2 was also preserved in these patients. These results suggest that
      the sinus conversion after mitral commissurotomy has an effect on the exercise
      performance of patients with MS and Af.

PMID- 7719500
TI  - Posterior mitral annuloplasty.

PMID- 7719501
TI  - Mitral annulus size in isolated mitral stenosis.
AB  - M-mode and two-dimensional echocardiographic images were obtained using the
      planimeter method in the short axis view and calculated by Doppler-derived
      pressure half-time in 24 patients with mitral stenosis before and after surgical
      commissurotomy and posterior annuloplasty. The diameter of the mitral valve
      annulus was measured in the standard long axis view and in the apical four
      chamber view using two-dimensional echocardiography. Preoperatively, the mitral
      annulus was dilated in all patients as a consequence of left atrial dilation.
      This could be one of the factors causing residual regurgitation after surgical
      mitral commissurotomy. However, more data are needed to demonstrate that
      annuloplasty can prevent the development of mitral regurgitation after surgery.

PMID- 7719502
TI  - Posterior annuloplasty in the surgical treatment of mitral insufficiency.
AB  - One hundred and twenty-nine patients underwent posterior mitral annuloplasty with
      a Gore-Tex tube for mitral regurgitation between January 1982 and June 1991. The
      hospital mortality was 1.5% (CL = 0.5%-2.5%). The overall survival of hospital
      survivors was 96.5% +/- 2.7% at five and 86.2% +/- 7.6% at nine years, freedom
      from cardiac death was 99.1% +/- 0.9% and 95.2% +/- 3.9%, respectively. The
      actuarial freedom from embolism was 96.1% +/- 2.3% at five and 88.5% +/- 5.5% at
      nine years. The freedom from endocarditis (one patient) was 100% and 92.6 +/-
      7.1%, respectively. Reoperation was necessary in six cases between one and 72
      months after the operation (mean 38.5 +/- 30.5 months). The etiology of the
      valvular insufficiency was rheumatic in all reoperated cases. The freedom from
      reoperation was 94.1% +/- 3.2% at five and 87.2% +/- 5.6% at nine years. There
      was no mortality at reoperation. Of the 117 patients alive at the end of follow
      up and not requiring reintervention, 113 (96.6%) showed good functional
      improvement and were in NYHA functional class I or II. We conclude that both the
      immediate and long-term results of reconstructive surgery using the technique of
      inserting a half-ring on the posterior mitral annulus compare favorably with
      those obtained using other annuloplasty methods.

PMID- 7719503
TI  - Annular remodelling with pericardial reinforcement: surgical technique and early
      results.
AB  - Of 127 consecutive patients who underwent surgical repair of degenerative mitral
      valve incompetence between 1986 and 1992, 55 received posterior annuloplasty
      reinforced by an autologous pericardial tube. All patients had echocardiographic
      assessment before surgery and at discharge from hospital. There was one hospital
      death (0.78%) and one patient (0.79%) required early reoperation because of
      suture dehiscence. Postoperative fluoroscopy and echocardiography ascertained
      excellent relieve of the mitral regurgitation without any distortion of the
      annulus. It is concluded that early results with autologous pericardial
      annuloplasty are very promising, and a prospective follow up study is underway to
      assess mid to long term results.

PMID- 7719504
TI  - Importance of the left ventricular subvalvular apparatus for cardiac performance.
AB  - The importance of the subvalvular mitral apparatus for left ventricular
      performance was studied in eight anesthetized dogs. During extracorporeal
      circulation St. Jude Medical mitral valve prostheses were implanted preserving
      the chordae tendineae. Flexible wires were slung around the chordae tendineae and
      brought to the outside through the left ventricular wall to cut the chordae
      tendineae by electrocautery in the closed beating heart. The left ventricular
      diameters were measured by sonomicrometry, left ventricular stroke volume and
      enddiastolic volume by dye dilution, and left ventricular pressure by catheter
      tip manometer. Data were collected at different preloads achieved by volume
      loading with blood before and after the chordae tendineae were cut. The results
      showed that after the chordae tendineae had been cut left ventricular systolic
      pressure, heart rate, diastolic and systolic diameters of the left ventricle
      along the minor axis were not different from the pre-cut values at any left
      ventricular enddiastolic pressure. However, significant differences were observed
      for maximum dp/dt (-15%), major axis diastolic diameter (+10%) and systolic
      shortening (-40%), enddiastolic volume (+18%) at any left ventricular
      enddiastolic pressure, and stroke volume (-24%) at any enddiastolic volume level.
      The data demonstrate that the subvalvular apparatus not only maintains
      physiologic valve function, but contributes significantly to left ventricular
      performance. The impairment of left ventricular function following removal of the
      subvalvular apparatus might be aggravated in pre-injured hearts in mitral valve
      disease. Consequently, the subvalvular apparatus should be preserved in mitral
      valve replacement whenever possible.

PMID- 7719505
TI  - Reoperation in patients with a bioprosthesis in the mitral position: indications
      and early results.
AB  - Our experience with 221 patients undergoing a first reoperation for bioprosthesis
      failure in the mitral position is reviewed. Most, (196, 89%) were reoperated
      because of structural valve deterioration, 16 (7%) had periprosthetic leak and
      nine (4%) had prosthetic endocarditis. Operative mortality (23 patients overall,
      10.4%) was significantly higher in those patients who were in NYHA functional
      class IV or had impaired left ventricular function, in those reoperated because
      of prosthetic endocarditis and those undergoing emergency reoperation. Those
      patients who had structural valve deterioration, good left ventricular function
      and who were reoperated electively had the lowest operative risk. With increasing
      experience and the use of standardized surgical techniques, the results of
      reoperation for bioprosthetic failure have improved considerably in recent years.
      A further reduction in operative risk can be expected with better patient
      selection, obtained through more careful non-invasive assessment of valve
      performance to detect the initial signs of bioprosthetic failure.

PMID- 7719506
TI  - High speed cine-radiographic study of aortic valve leaflet motion.
AB  - The leaflets of the aortic valve move extremely rapidly during opening and
      closing. To analyse this movement, radiopaque markers were placed on the aortic
      valves of four dogs during cardiopulmonary bypass. One to five months later the
      dogs were studied using x-ray, and the marker motion was recorded on cine-film at
      500 frames/second. Simultaneous aortic pressure varied from 70/30 to 188/152 mmHg
      and heart rate from 33 to 150 bpm. Analysis of 19 systolic periods and 2500 cine
      frames indicated that leaflet motion occurred in four phases: 1--rapid movement
      during initial opening, 2--a little movement near maximal excursion, 3--a slow
      movement during early closing and 4--a rapid movement to complete closure. Phases
      1 and 4 averaged 17.6 and 16.5 msec respectively, and were independent of heart
      rate, whereas the length of phases 2 and 3 varied with heart rate. The leaflets
      moved 82% of their maximum excursion during rapid opening and 53% during rapid
      closure. Leaflet curvature reversed in both the radial and the circumferential
      directions during opening. The leaflet profile in the radial direction changed as
      follows: during rapid opening, the belly of the leaflet moved outward, first
      causing the leaflet to straighten and then to conform to the profile of blood
      flow. During closure the belly of the leaflet moved centrally, causing the
      leaflet to curve toward the ventricle. The leaflet profile in the circumferential
      direction indicated that during opening the midpoint of the leaflet leads the
      motion towards the aortic wall.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719507
TI  - Transesophageal echocardiographic localization of an aortic valve papillary
      fibroelastoma during routine coronary artery bypass surgery.
AB  - Papillary fibroelastomas are rare, primary cardiac tumors most often diagnosed
      incidentally at autopsy. These tumors have been associated with embolism,
      neurologic injury, coronary ischemia and sudden death. We report a case of
      clinical detection of an asymptomatic aortic valve papillary fibroelastoma by
      transesophageal echocardiography. The mass was an incidental finding during
      routine coronary artery bypass surgery. This finding dictated a change in the
      operative approach to include resection of the aortic valve mass in addition to
      coronary revascularization.

PMID- 7719509
TI  - Lessons from the past: twenty-five years experience with the Cross-Jones caged
      disc prosthesis.
AB  - One hundred and twenty-one patients who received 145 Cross-Jones prostheses
      between 1967 and 1973 were followed for over 20 years. Thirty-six patients had
      undergone single aortic valve replacement, receiving an uncovered prosthesis
      (Group A), while 83 of the 85 patients in Group B undergoing isolated mitral or
      combined mitral and aortic and/or tricuspid replacements received a cloth-covered
      prosthesis in the mitral and/or tricuspid position. There were no mechanical
      failures in Group A, and three patients are alive 24 years after their
      operations. The seat was smooth in all prostheses inspected at autopsy and the
      disc was not worn even 15-18 years after surgery. The overall incidence of
      thromboembolism in this group was 3.56%/pty, of which 2.13%/pty were fatal. All
      operative offvivors with cloth-covered valves developed mechanical dysfunction
      leading to death or requiring reoperation within ten years. The cloth cover was
      invariably disrupted and the disc hitting this rough surface had become worn,
      with significant diminution in their diameters in all valves recovered during
      reoperation or at autopsy. In seven patients, the disc escaped from a mitral
      prosthesis causing immediate death, while one patient survived a tricuspid disc
      escape for over one month and was then successfully reoperated. The overall
      incidence of thromboembolism in Group B was 23.4%/pty, of which 11.7%/pty were
      fatal.

PMID- 7719508
TI  - Doppler sonographic evaluation of the Duromedics-Edwards bileaflet valve at five
      year follow up.
AB  - In order to define normal flow characteristics at mid-term follow up, prospective
      Doppler echocardiographic studies were performed in 145 patients (mean age 49.3
      years) with Duromedics-Edwards bileaflet valve prostheses (76 aortic, 55 mitral
      and 14 double aortic and mitral) at a mean interval of 5.2 years following
      operation. All patients had clinically normal prosthetic valve function and no
      clinical or radiographic signs of heart failure. None of the patients had
      severely impaired left ventricular function as assessed by cross sectional 2D
      echocardiography. Mean peak velocity across prostheses in the aortic position was
      2.8 +/- 0.5 m/sec, corresponding to a calculated instantaneous peak pressure
      gradient of 31.4 +/- 10.2 mmHg. Gradients varied inversely to valve size,
      although differences were significant only when comparing the 19mm and 21mm
      versus the 27mm valve (p < 0.05). In the mitral position the mean of peak
      velocity was 1.8 +/- 0.3 m/sec and pressure half time was 102 +/- 14 msec,
      representing a calculated mean orifice size of 2.2 +/- 0.5 cm2, with no
      significant difference between valves of different sizes. Paravalvular
      regurgitation was more common in the aortic than in mitral position (39% vs. 4%,
      p < 0.05), although in all cases it was mild (range less than one centimeter from
      prosthesis ring) and clinically insignificant. We conclude that normally
      functioning DE valve prostheses have a predictable range of Doppler
      echocardiographic parameters, although the individual variability of pressure
      gradients and effective valve area (in mitral valves) has to be emphasized.
      Nevertheless, the Duromedics Edwards valve shows good hemodynamic properties at
      mid-term follow up.

PMID- 7719510
TI  - Cryopreserved homografts in aortic and mitral prosthetic endocarditis: expanding
      the use of biological tissues in complex cardiac infections.
AB  - The case of a 27-year-old male heroin addict suffering from mitral and aortic
      prosthetic valve endocarditis is presented. Double valve re-replacement was
      performed using cryopreserved aortic homografts. Aortic root replacement with
      coronary re-implantation and intra-atrial valve implantation for mitral valve
      replacement were the techniques used. Despite the fatal outcome of this case, it
      clearly illustrates the possibilities of expanding the indications for combined
      complex replacement of heart valves by using fully biological tissue of human
      origin.

PMID- 7719511
TI  - Bioprosthetic cardiac valve degeneration: role of inflammatory and immune
      reactions.
AB  - Inflammatory and immune reactions are thought to mediate both calcification and
      biodegradation of bioprosthetic cardiac valve implants. To investigate the
      mechanisms of implant degeneration, we evaluated the role of inflammatory and
      immune reactions and the effects of tissue preservative treatment in three series
      of experiments. In the first experiment, three kinds of implants, i.e.
      glutaraldehyde-treated autograft Sprague-Dawley (SD) rat skin, xenograft Swiss
      Webster (SW) mouse skin, and saline-treated autograft (control) were
      subcutaneously implanted in ten weanling SD rats, and retrieved after 70 days.
      There was no significant difference in the level of calcification in the
      autograft (113.13 +/- 27.09 micrograms/mg dry weight) and xenograft (78.27 +/-
      31.53 micrograms/mg dry weight) (p > 0.05), but both differed significantly from
      the control specimens (1.55 +/- 0.87 micrograms/mg dry weight). In the second
      experiment, the immunological response to glutaraldehyde-treated bovine
      pericardium (glut tBP) and glycerol treated bovine pericardium (glyc tBP)
      implants were tested in vivo and in vitro. A Gore-Tex implant was used as a
      control. Sections of these materials were implanted to the abdominal muscle wall
      of Lewis rats, with each group composed of twelve animals. Lymphocytes and sera
      from the animals were isolated, and histological examination was performed at two
      or four weeks post-implantation. Collagen type 1 (calf skin) was used as antigen.
      Tritiated thymidine incorporation was used to measure lymphocyte response to
      antigen collagen type 1 (calf skin), and an Enzyme Linked Immunosorbent Assay
      (ELISA) was used to test antibodies. The results showed that lymphocytes from
      both the glut tBP and the glyc tBP groups responded to collagen type 1. The ELISA
      results showed that the glyc tBP group produced more antibodies than did the glut
      tBP group, with the difference being significant at a level of p < 0.02.
      Histology revealed that the glyc tBP had greater inflammatory changes and
      collagen degeneration than did the glut tBP. In the third experiment, sections of
      glut tBP and glyc tBP were implanted subcutaneously in two groups of ten weanling
      SD rats, and retrieved after 70 days. The results showed that glut tBP caused
      more calcification (197.04 +/- 83.56 micrograms/mg dry weight) than did the glyc
      tBP (6.74 +/- 0.55 microgram/mg dry weight), with the difference being
      significant at a level of p < 0.05. From these investigations it is concluded
      that tissue treatment prior to implantation was very important in determining the
      tendency of tissue to calcify, and that there was no obvious relationship between
      bioprosthetic calcification and immunogenicity.

PMID- 7719512
TI  - Effects of different antibiotics on the endothelium of the porcine aortic valve.
AB  - Homograft heart valves are usually sterilized by exposure to multiple-antibiotic
      solutions at 4 degrees C for 24 hours. Several combinations of antibiotics have
      been proposed and discussed in the literature, but their toxicity to cusp
      endothelium has not been investigated yet. We studied the endothelial cell
      viability of porcine aortic valves by measuring their in vitro prostacyclin
      (PGI2) production after being exposed to different antibiotics solutions. Porcine
      aortic valves were immersed for 24 hours at 4 degrees C in RPMI medium to which
      antibiotics (Gentamycin 80 micrograms/ml, Azlocillin 500 micrograms/ml,
      Cloxacillin 25 micrograms/ml, Metronidazole 100 micrograms/ml, Amphotericin B 50
      micrograms/ml, GACMA) were added separately or in combination. The basal and
      bradykinin (10 microM) stimulated PGI2 release of these valves in the medium were
      measured during consecutive incubation lasting 15 minutes at 37 degrees C, using
      a radioimmunoassay for 6-oxo-PGF1 alpha. Valves treated with the combination of
      all five antibiotics produced significantly less PGI2 in basal and stimulated
      conditions (1.64 +/- 0.63--7.25 +/- 1.73 ng/ml x cm2, p < 0.05) than the controls
      (4.66 +/- 0.66--30.55 +/- 3.84 ng/ml x cm2, p < 0.001). Although all antibiotics,
      when studied separately at the above mentioned concentrations, tended to reduce
      the biosynthesis of PGI2, amphotericin B was responsible for the most pronounced
      decrease in its production. The toxic effect of amphotericin B was dose
      dependent; at a low concentration (5 micrograms/ml), which is usually enough for
      antifungal action, toxicity was undetectable. At 50 micrograms/ml PGI2 production
      was half of that found at 5 micrograms/ml, although concentrations as high as 100
      micrograms/ml have been used clinically to disinfect homografts. Scanning
      electron microscopy (SEM) also confirmed the extensive loss of endothelium after
      exposure to high concentrations of amphotericin B. Our study suggests that the
      other four antibiotics used in the concentrations described above do not damage
      endothelial function; amphotericin B is also harmless if used at a concentration
      of 5 micrograms/ml.

PMID- 7719513
TI  - Which patients will require two or more reoperations for structural valve
      deterioration of porcine bioprostheses?

PMID- 7719514
TI  - Ischemic mitral regurgitation.

PMID- 7719515
TI  - Medical and nursing problems of children with neurodegenerative disease.
AB  - Little is written on the management of problems encountered by children with
      neurodegenerative disease. Whilst the conditions are individually rare, as a
      group of diseases they pose a considerable burden on the child, the family and
      the community. This study describes the 127 children with neurodegenerative
      disease who were admitted to Helen House, a hospice for children, from the time
      of opening in November 1982 until the end of 1993. The great majority of the
      conditions were genetic in origin and nearly one-third of the families had had
      two or more children with the same disease. Seventy-four (58%) of the children
      have died, with nearly half dying at home. The course of the disease was in many
      cases chronic and these children presented with multiple medical and nursing
      problems. Examination of the problems recorded in 1993 revealed that nearly all
      the children had no speech, or speech was impaired. Most were either totally
      immobile or had considerably reduced mobility. Seventy per cent of the children
      had feeding problems and one-quarter were fed through a nasogastric tube or
      gastrostomy. Thirty-five per cent of the children suffered pain on occasions,
      with muscle spasm being the main identifiable source of pain. Practical
      suggestions are made for the management of these children.

PMID- 7719516
TI  - Regional Study of Care for the Dying: methods and sample characteristics.
AB  - The Regional Study of Care for the Dying (RSCD) was established in 1990 with the
      dual aims of providing district health authorities with an audit of local
      services for the dying, and of addressing questions about experiences of people
      dying from cancer, effectiveness of hospice care, and needs of and appropriate
      service provision for people dying from causes other than cancer. The survey
      methods are described in this paper, together with the characteristics and
      representativeness of the sample. An interview survey was conducted of family or
      others who knew about the last year of life of a random sample of people who died
      in 1990. It was based upon methods used in nationally representative surveys by
      Cartwright in 1969, and Cartwright and Seale in 1987. The setting was 20 district
      health authorities, who paid for local data collection. Approximately 270 deaths
      were randomly sampled in each district: 5375 deaths were sampled in total. As
      cancer patients are the focus of most services for the dying, cancer deaths were
      sampled disproportionately (54%). Interviews were obtained for 69% (3696) of the
      sample. The response rate varied significantly by cause of death, age and social
      class of decreased, and the degree of deprivation of the district. There were
      small, but statistically significant, differences in cause of death and age
      between those deaths for whom interviews were obtained and national figures for
      deaths occurring in 1990. The discussion addresses key issues in the study,
      including responses from ethical committees, response rate and quality of
      data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719517
TI  - Terminal illness: views of patients and their lay carers.
AB  - This paper examines the responses of 28 terminally ill patients and their lay
      carers to identical questions about the patients' experiences in the month prior
      to their admission to an inpatient hospice. No statistically significant
      differences were found between the reports of patients or carers regarding the
      patients' activities of daily living, their physical symptoms, or the evaluations
      of the care they received. Discrepancies between accounts were most likely to
      concern the presence or absence of psychological symptoms, the degree of distress
      caused to patients by their symptoms, and the main symptoms experienced by the
      patient on their admission to the hospice. It is suggested that the accounts of
      patients' experiences given by their carers can be used as a valid source of
      information.

PMID- 7719518
TI  - Lymphangiosarcomata--experience in a lymphoedema clinic.
AB  - Two cases of patients attending a lymphoedema clinic and developing
      lymphangiosarcomata are described. The epidemiology, natural history and
      management of this uncommon malignancy are discussed and the pertinent features
      that should be sought by professionals involved in routine follow-up of patients
      prone to lymphoedema outlined.

PMID- 7719519
TI  - In defeat of the odds.

PMID- 7719520
TI  - Angina-linked syncope and lack of calcium antagonist therapy predict cardiac
      arrest before definitive diagnosis of vasospastic angina.
AB  - BACKGROUND: Several prognostic factors have been identified in patients with
      vasospastic angina; however, factors that would predict potentially fatal cardiac
      arrest during the period between the onset of angina and its definitive diagnosis
      remain unknown. We investigated the predictive value of the clinical findings
      that are available when a patient is hospitalized after a cardiac arrest but
      before a definitive diagnosis of vasospastic angina is made. METHODS: We compared
      the clinical findings in 11 patients who experienced cardiac arrest before
      vasospastic angina was definitively diagnosed (group I) with 81 patients with
      vasospastic angina without cardiac arrest (group II). The definitive diagnosis of
      vasospastic angina was made on the basis of results of coronary spasm provocation
      test or ECGs during spontaneous attacks, or both. RESULTS: The incidence of
      angina-linked syncope was significantly higher in group I than in group II (six
      out of 11 versus nine out of 81, P < 0.005). Significantly fewer group I patients
      were receiving calcium antagonists than group II patients (three out of 11 versus
      63 out of 81, P < 0.005). Serious arrhythmias were significantly more common in
      group 1 than in group II (seven out of 11 versus 12 out of 81, P < 0.005).
      Logistic regression analysis of the eight clinical variables available when first
      seen in the hospital indicated that angina-linked syncope and the lack of calcium
      antagonist therapy were independently related to risk of cardiac arrest.
      CONCLUSIONS: From the clinical findings available, a history of angina-linked
      syncope and lack of calcium antagonist therapy were found to be independent
      predictors of cardiac arrest before a definitive diagnosis had been made.
      Patients who have suspected vasospastic angina may benefit from early treatment
      with calcium antagonists if they have a history of angina-linked syncope.

PMID- 7719521
TI  - Abnormal platelet reactivity in men with premature coronary heart disease.
AB  - BACKGROUND: Continuous platelet aggregation does not occur in patients with
      stable coronary heart disease (CHD). However, there may be a latent potential for
      increased aggregation given appropriate stimuli, since increased in-vitro
      platelet aggregation appears to be predictive of cardiac events. This study
      evaluates the relationship between in-vitro platelet aggregation and coronary
      artery disease (CAD) as defined by angiography. METHODS: In-vitro platelet
      aggregation was assessed in a case-control study of 53 men with CHD younger than
      50 years, and in 48 control subjects without CHD who were matched for age, sex,
      and socioeconomic status. All major risk factors were evaluated. Semi
      quantitative composite scores of the extent of arterial wall involvement and
      composite scores for the severity of discrete lesions were documented from
      standard coronary angiography. Measures of platelet aggregation in response to
      adrenaline, adenosine diphoshate (ADP), and collagen included: (1) the maximum
      slope of the aggregation curve (rate); (2) lag time to 50% maximum aggregation
      (LT50%); and (3) the threshold concentration of each agonist to cause maximal
      aggregation. RESULTS: The CHD patients had larger platelets than patients in the
      control group (mean platelet volume 9.40 +/- 0.73 versus 8.88 +/- 0.87; P <
      0.01). The aggregation rate was significantly faster with adrenaline in the group
      with CHD than patients in the control group (rate of aggregation 13.9 +/- 8.8
      versus 8.6 +/- 4.0 cm/s respectively, mean +/- SD; LT50% for adrenaline 130 +/-
      70 versus 230 +/- 10 s respectively, mean +/- SD). Fewer CHD patients had no
      aggregation response to adrenaline than in the control group (8 versus 31%, P <
      0.05). Adrenaline-induced platelet aggregation, as measured by LT50% for
      adrenaline, weakly but significantly correlated with the number and severity of
      discrete obstructive coronary lesions (r = -0.28, P < 0.05). This association
      remained significant after multivariate regression analysis. No association was
      found between any measure of platelet reactivity and the extent of disease as
      measured by a semi-quantitative composite score; this measured the extent of
      disease of the coronary artery walls visible by angiography. CONCLUSIONS: These
      findings indicate that platelets from men with premature CHD are larger and
      aggregate more rapidly in response to platelet agonists, particularly adrenaline.
      An increased rate of aggregability with adrenaline predicted the severity of CAD
      lesion but not the extent of the disease, and this suggests that platelets play a
      role in the formation of localized obstructive lesions in coronary arteries, and
      therefore acute coronary events.

PMID- 7719522
TI  - Alterations in left ventricular shape in patients with angina and single-vessel
      coronary disease.
AB  - BACKGROUND: Left ventricular shape alterations, apparently independent of acute
      ischaemia or previous myocardial infarction, have been described in patients with
      stable angina. Our previous observations had been made in a group of patients
      with multivessel coronary disease; it was therefore not possible to establish a
      clear-cut anatomical relationship between the location of ischaemia and the
      changes in left ventricular contour. The aim of this work was to extend the
      previous observations by analysing left ventricular shape in patients with angina
      and single-vessel coronary disease, in whom the potentially ischaemic region can
      be easily localized. METHODS: Fifty-eight patients with stable or unstable angina
      were retrospectively selected if they had single-vessel disease, normal regional
      and global function and no previous myocardial infarction: 37 had a critical
      stenosis (more than 75% diameter reduction) of the left anterior descending
      artery and 21 had a critical stenosis of the right coronary artery. Patients with
      left ventricular hypertrophy or any other obvious cause of myocardial dysfunction
      were excluded. All patients underwent haemodynamic study. Left ventricular global
      shape was evaluated by calculating eccentricity and circular indices; regional
      curvature was measured at 90 points along the angiographic contours (right
      anterior oblique projection) by applying a windowed Fourier analysis. Results
      were compared with those obtained in 16 normal subjects. RESULTS: Patients had
      significant diastolic alterations in left ventricular shape, which assumed a more
      rounded aspect than normal. Regional curvature was significantly altered at
      several points pertaining to the anterior, apical and inferior segments. The
      pattern of changes in regional curvature was about the same in the left anterior
      descending and right coronary artery groups, with the involvement of regions
      supplied by angiographically normal arteries, although the extent of alteration
      was greater in patients with stable, chronic angina (more than 6 months) and in
      patients with stenosis of the left anterior descending artery. CONCLUSIONS:
      Patients with angina, no previous myocardial infarction and normal systolic
      function had left ventricular shape abnormalities either in the potentially
      ischaemic or in the remote zones. The mechanism leading to these changes is still
      speculative.

PMID- 7719523
TI  - Adrenoreceptors, endothelial function, and lipid profile: effects of atenolol,
      doxazosin, and carvedilol.
AB  - BACKGROUND: The use of effective blood-pressure-lowering drugs has not achieved
      the expected reduction in the incidence of ischaemic heart disease in
      hypertensive patients. This study examined the cardiovascular effects of
      adrenergic blockade (alpha or beta, or both) and its effect on the fibrinolytic
      response of the endothelium to anoxia and lipoprotein metabolism in 78
      hypertensive patients with ischaemic heart disease. METHODS: All patients had
      stable angina on positive exercise testing and silent ischaemia on 24 h Holter
      monitoring at baseline and 6 months after effective blood-pressure-lowering
      treatment with the selective beta-blocker atenolol, the alpha 1-inhibitor
      doxazosin, or the dual-action drug carvedilol. RESULTS: Atenolol increased the
      effort time (P < 0.05), total ischaemia (P < 0.05), and the number of ischaemic
      episodes (P < 0.05). It reduced the lipoprotein ratio (P < 0.05) but did not
      modify the fibrinolytic activity of the endothelium. Doxazosin increased the
      fibrinolytic index (ratio of plasminogen activator to its main inhibitor) before
      (P < 0.05) and after anoxia (P < 0.0001) and the lipoprotein ratio (P < 0.001),
      without an anti-ischaemic effect. Carvedilol increased the effort time (P <
      0.05), reducing total ischaemia (P < 0.05), the number of ischaemic episodes (P <
      0.01), and increasing the post-anoxia fibrinolytic index (P < 0.05) without
      modifying the lipid profile. CONCLUSIONS: At antihypertensive equipotent doses,
      the inhibition of alpha 1-receptors improves the endothelial fibrinolytic
      activity and the lipid profile. beta-Blockade has an anti-ischaemic action, but
      reduces the lipoprotein ratio (ApoA/ApoB) and does not improve endothelial
      fibrinolytic activity.

PMID- 7719524
TI  - Thrombolytic and antithrombotic efficacy of the platelet GPIIb-IIIa antagonist
      DMP728.
AB  - OBJECTIVE: This study was undertaken to determine the antithrombotic and
      thrombolytic efficacy of DMP728 alone and in conjunction with thrombolytic
      agents. BACKGROUND: Coronary artery reocclusion continues to be a significant
      clinical problem after thrombolytic therapy or balloon angioplasty, with
      incidence rates of 5-20% regardless of thrombolytic intervention. To date, no
      adjunctive therapy has been shown to eliminate the incidence of rethrombosis
      after thrombolysis. DMP728, a novel small-molecular-weight platelet GPIIb-IIIa
      receptor antagonist, has been shown to prevent rethrombosis after thrombolysis in
      various arterial thrombosis models in dogs. It might therefore have potential
      utility in optimizing the clinical outcome of currently available thrombolytic
      agents. The present investigation was designed to examine the thrombolytic
      potential of DMP728 alone and in conjunction with different thrombolytic agents.
      METHODS: The deaggregatory effect of DMP728 in reversing human platelet
      aggregation after initiation of platelet aggregation by 10 mumol/l adenosine 5'
      diphosphate was determined using light-transmittance aggregometry. The in-vitro
      efficacy of DMP728, alone and in combination with thrombolytic drugs, in
      dispersing a preformed platelet-rich clot was determined using a clot-dispersion
      assay. In addition, the in-vivo thrombolytic effects of DMP728, alone and in
      conjunction with streptokinase, were examined in an electrolytically induced
      femoral artery thrombosis model in dogs. RESULTS: DMP728 had concentration
      dependent deaggregatory and thrombolytic effects in reversing aggregates and in
      dispersing a preformed platelet-rich thrombus in vitro. Furthermore, it exhibited
      significant potentiation (P < 0.01) when combined with different thrombolytic
      drugs such as streptokinase, tissue-type plasminogen activator (t-PA) and
      urokinase in lysing platelet-rich thrombus. DMP728 had significant in-vivo
      thrombolytic effects along with synergy in fully restoring arterial flow upon its
      concomitant use with subeffective to ineffective doses of streptokinase in an
      electrolytically induced femoral artery thrombosis model in dogs. It also reduced
      the time to reperfusion and prevented the incidence of rethrombosis after
      streptokinase. CONCLUSIONS: These findings suggest the potential utility and
      benefits of DMP728, not only in preventing arterial thrombosis but also in
      optimizing the efficacy of thrombolytic drugs.

PMID- 7719525
TI  - Accelerated intravenous dosing of recombinant tissue-type plasminogen activator
      causes rapid but unstable reperfusion in a canine model of acute myocardial
      infarction.
AB  - BACKGROUND: Accelerated intravenous dosing is currently the preferred regimen for
      administering recombinant tissue-type plasminogen activator (rt-PA) in acute
      myocardial infarction (AMI). This regimen is recommended on the basis of clinical
      angiographic studies that reported superior 60 and 90 min patency rates. However,
      continuous infarct-vessel flow characteristics after reperfusion following this
      regimen are poorly described. The aim of our study was an improved definition of
      the characteristics of infarct-vessel flow induced by intravenous accelerated rt
      PA using an animal model of acute coronary artery thrombosis. METHODS: We studied
      the characteristics of reperfusion induced by an accelerated intravenous rt-PA
      dosing regimen in a canine coronary artery thrombosis model that simulates AMI.
      We created a critical stenosis in the left anterior descending coronary artery
      (LAD) of 24 open-chest dogs. Thrombosis was caused immediately proximal to the
      stenosis by injection of a blood and thrombin mixture into a segment of the LAD
      which had intimal damage. Hemodynamics and distal LAD blood flow velocity were
      recorded continuously. Six animals did not complete the protocol. Animals in the
      treatment group (n = 10) received an intravenous accelerated rt-PA regimen (1.25
      mg/kg total dose) and were observed for 150 min. Eight animals served as
      controls. RESULTS: None of the control animal arteries reperfused. In the
      treatment group, reperfusion occurred 31.5 +/- 7.3 min after starting rt-PA
      dosing in two general patterns. In one pattern, reperfusion onset was gradual and
      linear; in the other pattern, reperfusion was sudden. LAD flow was cyclical in
      all animals, with marked variations in magnitude compared with baseline (0-173%
      of baseline). Reocclusion was common and occurred 30.3 +/- 6.3 min after the
      initial reperfusion. There were 1.9 +/- 0.4 reocclusions per animal, and two
      distinct patterns were noted. In one, flow ceased abruptly and, in the second,
      flow declined gradually in a linear fashion before stopping. Infarct-vessel flow
      was evident for 103.1 +/- 14.1 min of the 150 min observation period.
      CONCLUSIONS: Reperfusion occurs rapidly after an accelerated dosing regimen of rt
      PA. However, the infarct-vessel flow resulting from this therapy is unstable and
      is associated with early reocclusion and marked variation in flow magnitude.
      Analysis of continuous infarct-vessel flow velocity patterns suggests at least
      two different mechanisms for the onset of reperfusion and reocclusion after this
      therapy. Recognizing several mechanisms of arterial opening and closing may have
      important implications for methods of stabilizing infarct vessels after
      reperfusion by accelerated dosing of rt-PA.

PMID- 7719526
TI  - The natural history of postischemic T-wave inversion: a predictor of poor short
      term prognosis?
AB  - BACKGROUND: This study followed up the natural history of T-wave inversion and
      assessed the short-term prognosis associated with the condition. METHODS: Forty
      patients with acute ischemic syndrome, without infarction, and with postischemic
      T-wave inversion (group 1) were followed during the persistence (inverted T-wave
      period) and after the resolution of T-wave inversion (positive T-wave period).
      Another 40 patients with acute ischemic syndrome, without infarction and with
      normal T waves (group 2), were also followed. RESULTS: Postischemic inverted T
      waves showed resolution within 3-21 days of presentation in 31 patients from
      group 1 on medical treatment alone. Further ischemic events (acute myocardial
      infarction, acute ischemic syndrome, angina pectoris, silent ischemia), inducible
      ischemia (during treadmill test), wall-motion abnormalities (demonstrated by
      echocardiography), all developing in the primarily ischemic myocardial area, were
      more frequent (P < 0.02) in group 1 patients during the inverted T-wave period
      compared with those experienced in the positive T-wave period of group 1
      patients, and compared with group 2 patients. CONCLUSION: In most patients on
      medical treatment, postischemic inverted T-waves tended to resolve within 3
      weeks. The presence of postischemic inverted T waves appears to be an independent
      marker of further ischemic events.

PMID- 7719528
TI  - Bibliography of the current world literature.

PMID- 7719527
TI  - Weak allergenicity of recombinant hirudin CGP 39393 (REVASC) in immunocompetent
      volunteers. The European Hirudin in Thrombosis Group (HIT Group).
AB  - BACKGROUND: As a result of their polypeptidic nature, hirudins could
      theoretically elicit an immunologic response in humans. METHODS: The present open
      survey evaluates the allergenic potential of recombinant hirudin CGP 39393
      (REVASC) after repeated intravenous or subcutaneous exposures in immunocompetent
      volunteers with no known previous exposure to hirudins. Clinical signs and
      symptoms of allergic manifestations and surrogate markers of allergy (i.e.
      response to skin tests) were collected before and after each administration of
      CGP 39393. Hirudin-specific immunoglobulin (Ig)G or IgE antibodies were measured.
      RESULTS: Two hundred and sixty-three healthy volunteers were eligible, of whom
      12.2% had a history of allergy and 18.3% had a high level of total IgE. No signs
      or symptoms of allergy directly attributable to CGP 39393 were reported, either
      during or immediately after a first challenge. Irritative skin reactions, to
      either the prick or the intradermal skin test, were observed in eight volunteers
      28-56 days after the challenge. Three out of 200 volunteers exposed to a second
      course of CGP 39393 showed signs and symptoms of an allergic reaction. In all but
      one subject with a pruritic erythema it was possible to rule out a causative role
      for CGP 39393 (0.50%, 95% confidence limits [CL] 0.01-2.75). Three other
      volunteers displayed a suspect or a positive immediate-type skin reaction to the
      follow-up intradermal skin test without any signs or symptoms of allergy. Another
      asymptomatic volunteer (0.80%, 95% CL: 0.02-4.41) developed a low [i.e. 1+ on the
      radio-allergosorbent test (RAST) scale] but measurable titre of hirudin-specific
      IgE antibodies after the second exposure to CGP 39393. A third exposure in five
      volunteers was clinically uneventful. A positive reaction to the prick test and
      to the intradermal skin test was observed in one individual. CONCLUSIONS:
      Recombinant hirudin CGP 39393 appears to be a weak allergen. Repeated exposures
      are safe in fully immunocompetent subjects, including those with a history of
      previous allergies and high levels of total IgE. Type I allergic reactions are
      rare (i.e. less than 1%) after a second exposure and are limited to the skin.
      Routine skin tests are not needed to identify patients at risk of developing type
      I allergic reactions. Hirudin-specific IgE antibodies are rarely seen and then at
      very low titres.

PMID- 7719529
TI  - FDA panel gives cautious signal to summit.

PMID- 7719530
TI  - Comparison of astigmatic axis in the seated and supine positions.
AB  - BACKGROUND: Refractive error is assessed in the seated position while
      keratorefractive procedures are performed in the supine position. Since position
      induced ocular torsion could yield suboptimal results from improper axis
      alignment, this study was undertaken to ascertain whether ocular cyclotorsion
      occurs when a subject moves from a seated to supine position. METHODS: Fifty eyes
      of 29 subjects with refractive cylinder greater than 0.50 diopters were enrolled.
      Refraction was done with a phoropter and the correction was placed in a trial
      frame using plus cylinder. Astigmatic axis was determined in the seated and
      supine positions for 32 eyes by utilizing the "rocking the cylinder" technique
      and for 32 eyes using the Jackson cross cylinder. Both techniques were used for
      14 eyes. RESULTS: No statistically-significant difference for cylinder axis
      measured in the seated versus supine position was observed using the rocking the
      cylinder (4.3 degrees standard deviation [SD], 3.5 degrees, range 0 degrees to 13
      degrees, p = NS) or the Jackson cross cylinder methods (2.3 degrees, SD, 1.9
      degrees, range 0 degrees to 7 degrees, p = NS). Approximately 25% of eyes had a
      change in axis of 7 degrees to 16 degrees. CONCLUSIONS: These data suggest that
      the cylinder axis does not change significantly or predictably when most subjects
      move from the seated to supine position. The Jackson cross cylinder method seems
      more accurate and reproducible than the rocking the cylinder technique in
      determination of astigmatic axis under these circumstances.

PMID- 7719531
TI  - Effect of peripheral deepening of radial keratotomy incisions.
AB  - BACKGROUND: Single and double deepening of the peripheral part of radial
      keratotomy incisions are used to increase the refractive effect. METHODS: Single
      peripheral deepening was performed in 52 eyes of 36 patients and double
      peripheral deepening in 19 eyes of 14 patients who received radial keratotomy.
      RESULTS: In the single peripheral deepening group, the mean change in refractive
      power was 4.01 diopters (D); 53.8% of eyes were within +/- 1.00 D of emmetropia;
      residual myopia was greater than -1.00 D in 46.2% of eyes; 65.4% of eyes achieved
      an uncorrected visual acuity greater than or equal to 20/40. In the double
      peripheral deepening group, the mean change in refractive power was 5.07 D; 52.6%
      of eyes wee within +/- 1.00 D of emmetropia; residual myopia was greater than 
      1.00 D in 47.4% of eyes; 89.4% of eyes achieved an uncorrected visual acuity
      greater than 20/40. The difference in mean dioptric change between the standard
      radial keratotomy groups and the single and double peripheral deepening groups
      was 0.53 D and 0.47 D, respectively. CONCLUSIONS: Considering the limited
      additional dioptric change compared with the standard radial keratotomy surgical
      technique and the increased rate of complications, we think that peripheral
      deepening in radial keratotomy should be avoided.

PMID- 7719532
TI  - Visual function one year after excimer laser photorefractive keratectomy.
AB  - BACKGROUND: The purpose of this study is to investigate retrospectively the
      visual function of eyes 1 year after photorefractive keratectomy. METHODS: Visual
      function was assessed in 34 eyes of 22 patients who had undergone excimer laser
      surgery (Summit Excimed UV200). The mean time after surgery was 12.3 months.
      Twenty eyes of 20 age-matched normal subjects served as controls. The following
      tests were used: high and low contrast logMAR visual acuity, Pelli-Robson
      contrast sensitivity, and straylightmeter scores at 3.5 degrees and 10 degrees.
      RESULTS: There was a significant difference between scores obtained for the
      photorefractive keratectomy population and the control (p < .001, ANOVA). Fifty
      six percent (18/32) of the excimer treated eyes fell outside the 95% confidence
      limits of the normal data in at least one test of visual function; 22% (7/32)
      fell outside in at least 3 out of 5 tests. CONCLUSIONS: Some eyes showed reduced
      visual function 1 year after excimer surgery compared to age-matched normal
      controls. These deficits can only be detected fully when psychophysical tests in
      addition to visual acuity are employed.

PMID- 7719533
TI  - Effects of laser photocoagulation on corneal neovascularization in rabbits.
AB  - BACKGROUND: Corneal neovascularization is a common clinical entity. Although
      visual acuity is usually impaired and corneal function compromised, there has
      been only limited success in the clinical management of this condition. We
      evaluated the efficacy of laser photocoagulation of neovascularization in the
      rabbit cornea. METHODS: New vessel formation was provoked by the placement of
      sutures in the corneas. Rose bengal was injected intravenously and new vessels in
      the upper part of the corneas were treated with an argon laser. The lower halves
      were used as controls. Eighteen rabbits were divided into 2 groups. In group A
      neovascularization was treated 28 days after suture removal, when corneal
      inflammation had regressed. In group B treatment was performed 3 days after
      suture removal, when the cornea still exhibited marked inflammation.
      Postoperatively, the corneas were studied by slit-lamp microscopy, fluorescein
      angiography, and light, as well as electron microscopy. RESULTS: In group A,
      treatment led to the immediate occlusion of the vessels and to their gradual
      disappearance during the course of 3 months. In group B, no occlusion was seen
      during the 3-month follow-up period. The main histologic findings in the occluded
      vessels were endothelial cell disruption and degeneration, and the formation of
      clots. CONCLUSION: Our results suggest that argon laser photocoagulation using
      rose bengal is an effective method of occluding corneal new vessels, providing
      there is no corneal inflammation at the time of treatment.

PMID- 7719534
TI  - Treatment of corneal abrasions with soft contact lenses and topical diclofenac.
AB  - BACKGROUND: Treatment of corneal abrasions often involves antibiotic ointment and
      pressure patching. The corneal abrasions following excimer laser photorefractive
      keratectomy have been managed with disposable soft contact lenses and diclofenac
      (Voltaren) eye drops. METHODS: We report 13 patients with corneal abrasions from
      trauma or recurrent corneal erosions treated with application of a disposable
      soft contact lens and instillation of diclofenac and antibiotic eye drops.
      RESULTS: All 13 patients reported significant pain relief and all abrasions
      healed within 3 days (most within 24 hours). Two of the recurrent erosion
      patients suffered subsequent spontaneous abrasions and one of the traumatic
      abrasion patients developed a possible infectious keratitis which cleared without
      visual loss. CONCLUSIONS: In this small series, the combination of a disposable
      soft contact lens and the instillation of diclofenac drops provided significant
      pain relief while the abrasion healed and allowed the patients to function with
      binocular vision. This treatment regimen offers an alternative to pressure
      patching in the treatment of corneal abrasions.

PMID- 7719535
TI  - Simple method of transscleral fixation of a posterior chamber intraocular lens in
      the absence of the lens capsule.
AB  - BACKGROUND: There are several advantages to implanting a posterior chamber
      intraocular lens (IOL) in the ciliary sulcus when the lens capsule is absent. I
      have developed a simple method of fixating an IOL into the ciliary sulcus which
      does not require different needles, multiple needle passes, scleral dissection,
      or awkward surgical maneuvers. METHODS: Thirty eyes were enrolled in this study.
      All eyes were either aphakic, requiring a secondary lens implantation, or
      required IOL exchange. The patients were followed for 30 months. Using a single
      10-0 double-armed, polypropylene suture, a through-and-through infraciliary
      scleral pass secured each haptic without tying. The lens was then positioned into
      the ciliary sulcus and the knots tied outside the eye under direct visualization.
      RESULTS: This procedure has been used in 30 eyes without erosion of sutures,
      dislocation or tilting of the IOL, or induced astigmatism. Twenty-one eyes (70%)
      had spectacle-corrected visual acuity of 20/40 or better. CONCLUSION: The results
      of this study demonstrate that posterior chamber transscleral fixated IOLs give
      improved postoperative visual results.

PMID- 7719537
TI  - Mastel Byron Radial Keratotomy Guide.

PMID- 7719536
TI  - Presumed epithelial cyst in the anterior chamber following refractive keratotomy.
AB  - BACKGROUND: A free floating cyst in the anterior chamber was observed 10 days
      after a 35-year-old woman underwent an eight-incision radial keratotomy and two
      incision transverse keratotomy of the left eye. METHODS: A single self-sealing
      microperforation had occurred on the inferotemporal incision during the initial
      surgery, which used a two direction incision technique. RESULTS: A free floating
      cystic structure was first noted by the surgeon 10 days after surgery, when the
      patient returned for repeated surgery for residual myopia. After 18 months, there
      was little change in the size or appearance of the cyst. The patient, who was
      informed of the complication, remained asymptomatic with uncorrected visual
      acuity of 20/25 + 2 bilaterally. Because of the lack of growth of the cyst,
      continued observation was chosen instead of surgical removal. The cause of the
      cyst is unknown. CONCLUSION: A free floating cyst in the anterior chamber may
      occur after refractive keratotomy.

PMID- 7719538
TI  - Keratoconus in a donor cornea.

PMID- 7719539
TI  - Corticosteroid treatment of regression after photorefractive keratectomy for
      myopia.

PMID- 7719540
TI  - Deep lamellar keratotomy after overcorrected excimer laser myopic keratomileusis.

PMID- 7719541
TI  - Clinical and physiologic comparison of laparoscopic and open Nissen
      fundoplication.
AB  - BACKGROUND: Although recent reports have documented the safety and efficacy of
      laparoscopic fundoplication, none have compared outcomes to that of open Nissen
      fundoplication. STUDY DESIGN: Eighty-one patients had either open (n = 47) or
      laparoscopic (n = 34) Nissen fundoplication. Relief of symptoms was measured by a
      standardized questionnaire and scored by a modified Visick-Index. Physiologic
      outcome was assessed by postoperative pH monitoring and manometry in a subset of
      both groups. RESULTS: Primary symptoms were heartburn in 55 percent of the
      patients, regurgitation in 9 percent, dysphagia in 11 percent, and atypical in 25
      percent of patients. Twenty-seven (84 percent) of 32 patients in the laparoscopic
      group and 31 (84 percent) of 37 patients in the open group were cured or
      improved. Operative time was significantly longer in the laparoscopic group (218
      compared to 168 minutes). The period of hospitalization was shorter for the
      laparoscopic group (4.7 compared to 9.2 days, p < 0.0001). Postoperative
      pressures in the lower esophageal sphincter (LES) were significantly higher in
      the laparoscopic group (20.9 compared to 12.1, p = 0.006). Augmentation of
      sphincter length was similar for both groups. More patients in the laparoscopic
      group failed to relax their LES completely after fundoplication (32 compared to
      71 percent, p = 0.1). CONCLUSIONS: Symptomatic outcome after laparoscopic
      fundoplication is similar to that of open surgery. Physiologic studies reveal a
      greater augmentation of LES pressure and a low prevalence of sphincter relaxation
      after laparoscopic fundoplication.

PMID- 7719543
TI  - Elective lymph node dissection in patients with primary melanoma of the trunk and
      limbs treated at the Sydney Melanoma unit from 1960 to 1991.
AB  - BACKGROUND: The value of elective lymph node dissection (ELND) in melanoma
      remains controversial. Published prospective and retrospective studies can be
      criticized, and results from two ongoing randomized trials are not yet available.
      A previous retrospective review from the Sydney Melanoma Unit (SMU) showed
      apparent survival benefit from ELND, especially in tumors of intermediate
      thickness. STUDY DESIGN: We undertook a retrospective analysis of all patients
      treated at the SMU since 1960 for melanoma of the trunk or limbs measuring 1.5 mm
      or more in thickness, without clinical lymph node metastases, whose definitive
      wide excision (WE) with or without ELND was performed at the SMU within 60 days
      of initial diagnosis. RESULTS: There were 1,278 patients who fulfilled these
      criteria. Of these, 845 (66 percent) were treated with ELND and the remaining 34
      percent were treated with WE alone. The median follow-up period was 58 months.
      Patients with thicker tumors and younger age more commonly underwent ELND. Among
      patients with thinner tumors, males underwent ELND more commonly than females. A
      multivariate proportional hazard model of melanoma-specific survival stratified
      by tumor thickness was chosen to allow for the imbalances between the two groups.
      With or without allowance for covariates, no benefit from ELND was found in the
      whole group or any subset. In contrast to previous studies from the SMU, we
      deliberately excluded from the present study patients referred only after WE with
      or without ELND elsewhere, because these might have been a selectively biased
      poor prognostic group. CONCLUSIONS: This study does not indicate a benefit from
      ELND for melanomas of the trunk or limbs measuring over 1.5 mm in thickness.

PMID- 7719544
TI  - Small bowel necrosis associated with postoperative jejunal tube feeding.
AB  - BACKGROUND: Postoperative enteral nutrition using jejunal tube feeding is widely
      practiced and usually well tolerated. Functional intestinal complaints occur
      frequently but generally respond to alteration of the infusion rate or tube
      feeding formula. Occasionally, however, nonspecific signs of intestinal
      disturbance progress to a syndrome of abdominal distention, hypotension, and
      hypovolemic shock resulting in extensive small bowel necrosis. STUDY DESIGN:
      During a six-year period, four patients have been identified retrospectively who
      had this complication among 1,359 patients receiving jejunal tube feeding. Their
      clinical course was evaluated critically and compared with 11 cases described in
      the literature. RESULTS: Small bowel necrosis is a rare but highly morbid
      complication associated with postoperative jejunal tube feeding. Of 14 patients
      who had small bowel necrosis develop, 12 succumbed to this complication. The
      causative mechanism remains unclear, but is most likely the result of several
      factors. CONCLUSIONS: Tube feeding should be discontinued immediately and total
      parenteral nutrition should be considered in patients who have abdominal pain,
      abdominal distention, increased nasogastric drainage, and signs of intestinal
      ileus.

PMID- 7719542
TI  - Prospective analysis of outcome after cardiopulmonary resuscitation in critically
      ill surgical patients.
AB  - BACKGROUND: This study was done to examine the outcome of cardiopulmonary
      resuscitation (CPR) in the surgical intensive care unit (SICU) and to identify
      factors preceding cardiopulmonary arrest that could predict survival. STUDY
      DESIGN: We prospectively collected demographic, laboratory, diagnostic, and
      complications data in our SICU database on 5,237 consecutive patients and
      reviewed the charts of all patients receiving CPR. RESULTS: Cardiopulmonary
      resuscitation was performed upon 1.1 percent (55 of 5,237 patients) of patients
      in the SICU. Twenty-nine percent (16 of 55 patients) survived greater than 24
      hours but died in the hospital, and 13 percent (seven of 55 patients) survived to
      discharge. No patient with a worsening Glasgow Coma Scale (GCS) score, acute
      physiology score (APS), or any acute organ failure who had cardiopulmonary arrest
      survived. Survival after CPR for patients with a stable or improving APS was 32
      percent (p < 0.01). CONCLUSIONS: Patients in the SICU who survived CPR had a
      stable or improving clinical course as determined by APS and GCS score, and had
      not had acute organ failure. Patients who were critically ill with a declining
      clinical course did not survive after CPR.

PMID- 7719545
TI  - Early regional expression and secretion of peptide YY and enteroglucagon after
      massive resection of small bowel.
AB  - BACKGROUND: Previous studies suggest that peptide YY (PYY) and enteroglucagon
      have an important role in intestinal adaptation after massive small bowel
      resection. This study was done to define the mechanisms, timing, and anatomic
      distribution of the PYY and enteroglucagon response. STUDY DESIGN: Lewis rats
      underwent resection of 70 percent of the small bowel (leaving equal segments of
      jejunum and ileum), transection, or laparotomy alone. Jejunum, ileum, and colon
      were compared in resected, transected, and control bowel six hours, 24 hours, one
      week, and two weeks postoperatively. RESULTS: Analysis of DNA, RNA, and protein
      per cm of bowel demonstrated hyperplastic changes. Radioimmunoassay revealed
      plasma PYY and enteroglucagon to be significantly elevated 24 hours after
      resection and they remained so through week two. In contrast, tissue PYY and
      enteroglucagon content decreased significantly in all tissues (p < 0.05) after
      resection. Reverse transcriptase polymerase chain reaction and Southern blot
      analysis demonstrated an immediate and sustained increase in PYY messenger RNA
      (mRNA) in both the ileum (fourfold) and in the colon (2.5-fold) at six hours (p <
      0.05). A gradual increase in PYY mRNA was also demonstrated in the jejunum with
      significance at two weeks (p < 0.05). Proglucagon mRNA was significantly higher
      in the jejunum, compared with the ileum and colon, at 24 hours, one week, and two
      weeks postresection. CONCLUSIONS: Alterations in PYY and enteroglucagon synthesis
      occur early in the ileum and colon after massive small bowel resection. The
      residual jejunum, however, is primarily responsible for the adaptive
      hyperenteroglucagonemia. These findings suggest that although PYY and
      enteroglucagon are colocalized to the same cell type, there is a gene-specific
      response for these two peptides after resection.

PMID- 7719546
TI  - The incidence, management, and outcome of patients with gastrointestinal
      carcinoids and second primary malignancies.
AB  - BACKGROUND: A higher than expected incidence of second primary malignancies in
      patients with gastrointestinal carcinoids has been reported. How patients with
      such concurrent neoplasms should be managed and whether or not the discovery of
      an incidental carcinoid at the time of operation for another malignancy affects
      patient management or outcome, has never been previously addressed. STUDY DESIGN:
      We retrospectively reviewed our 20-year experience with gastrointestinal
      carcinoid tumors with the purpose of determining the appropriate management and
      eventual outcome of patients with these multiple malignancies. RESULTS: Sixty
      nine patients with carcinoids of the gastrointestinal tract were discovered, of
      whom 29 (42 percent) had second synchronous tumors and three (4 percent) had
      metachronous tumors. The gastrointestinal tract accounted for 42.9 percent of the
      tumors, and carcinoma of the colon and rectum was found in seven (21.9 percent)
      of 32 patients. None of the 29 patients with a second synchronous tumor presented
      with symptoms referable to their carcinoid, each of which was incidentally
      discovered: nine at autopsy and 20 at laparotomy for the treatment of other
      tumors. All of the 20 surgical patients had the gastrointestinal carcinoids
      resected for cure, although three had histopathologic criteria for invasion. None
      of the 29 patients died as a result of, had recurrence of, or had their
      postoperative therapy altered by the carcinoid diagnosis. CONCLUSIONS:
      Gastrointestinal carcinoid is associated with a high incidence of second primary
      malignancy, 46 percent in this study. The most common site for the second primary
      malignancy in these patients is the gastrointestinal tract, suggesting a site
      specific predisposition to malignant degeneration. Most gastrointestinal
      carcinoids are incidentally discovered at laparotomy or autopsy. The discovery of
      an asymptomatic gastrointestinal carcinoid during the operative treatment of
      another malignancy will usually only require resection without additional
      treatment and will have little affect on the prognosis of the individual.

PMID- 7719547
TI  - Incidence, complications, treatment, and outcome of ulcers of the upper
      gastrointestinal tract after renal transplantation during the cyclosporine era.
AB  - BACKGROUND: Ulcers of the upper gastrointestinal tract after renal
      transplantation have been reported as a frequent and often lethal complication.
      Considering the continuous expansion of renal recipient criteria, we reviewed our
      experience with post-transplant ulcers after 1,034 renal transplants performed
      during the cyclosporine era. STUDY DESIGN: Our retrospective study analyzed only
      endoscopy-proven ulcers of the esophagus, stomach, and duodenum in 439 (42
      percent) living related adult recipients and 595 (58 percent) cadaver or living
      unrelated adult recipients. For ulcer prophylaxis, only oral antacids were
      routinely given post-transplant. RESULTS: There were 41 ulcers in 33 patients
      (esophageal: n = 5, 12 percent; gastric: n = 17, 42 percent; duodenal: n = 19, 46
      percent). Significant complications (n = 16) included 15 bleeding episodes and
      one perforation. The pathogenesis was viral in seven cases (gastric: n = 6, 15
      percent; duodenal: n = 1, 2 percent). The ulcers occurred significantly earlier
      post-transplant in cadaver or living unrelated compared with living related
      recipients (median, 53 compared with 508 days, p = 0.02). Nonoperative treatment
      was successful for 96 percent of all ulcers. We found no ulcer-related mortality
      or graft loss. For living related recipients, the actuarial graft survival rate
      at three years was 69 percent for patients with ulcers compared with 86 percent
      for those without ulcers (p = 0.02); for cadaver or living unrelated recipients,
      it was 48 percent for patients with ulcers compared with 77 percent for those
      without ulcers (p = 0.9). For living related recipients, the actuarial patient
      survival rate at three years was 92 percent for patients with ulcers compared
      with 93 percent for those without ulcers (p = 0.8); for cadaver or living
      unrelated recipients, it was 59 percent for patients with ulcers compared with 88
      percent for those without ulcers (p = 0.002). CONCLUSIONS: With more specific
      immunosuppression and more effective antiviral therapy, the incidence of post
      transplant ulcers is low. Considering the excellent results of nonoperative ulcer
      therapy and a zero percent ulcer-related mortality rate, renal transplantation is
      safe for patients with specific (e.g., ulcer history) as well as nonspecific
      (e.g., chronic obstructive pulmonary disease) ulcer risk factors.

PMID- 7719548
TI  - Recurrent pelvic support defects after sacrospinous ligament fixation for vaginal
      vault prolapse.
AB  - BACKGROUND: Multiple studies have shown sacrospinous ligament fixation to be
      highly effective therapy for vaginal vault prolapse. Several authors have
      suggested that the marked vaginal retroversion subsequent to sacrospinous
      ligament fixation may predispose to recurrent pelvic support defects in the
      anterior fascial segment, resulting in cystocele or urethrocele, or both. STUDY
      DESIGN: Thirty-six patients, 46 to 86 years of age, were examined at six weeks
      postoperatively and at long-term follow-up evaluation 15 to 79 months (median of
      42 months) after sacrospinous ligament fixation and repair of associated pelvic
      support defects. The examinations, by an unbiased examiner, were done to identify
      and grade recurrent pelvic support defects. RESULTS: At the six week
      postoperative visit, one patient had a small enterocele, and none of the patients
      demonstrated vaginal vault prolapse. At the long-term follow-up visit, 33 (92
      percent) of the patients had cystoceles, six (17 percent) had rectoceles, two (6
      percent) had enteroceles, and three (8 percent) demonstrated recurrent vaginal
      vault prolapse. Most cystoceles were small and asymptomatic. CONCLUSIONS: A high
      rate of success in the treatment of prolapse of the upper vagina by sacrospinous
      ligament fixation was observed. Pelvic support defects at long-term follow-up
      evaluation occurred more commonly in the anterior fascial segment. Retroversion
      and fixation of the upper vagina predisposes the anterior fascial segment to
      excess pressure and a higher incidence of cystocele than could be attributed to
      the effects of aging and menopause.

PMID- 7719549
TI  - A combined hospital experience with fundoplication and gastric emptying procedure
      for gastroesophageal reflux in children.
AB  - BACKGROUND: Operative treatment of symptomatic gastroesophageal reflux (GER),
      often together with neurologic feeding disorders, is very common in infancy and
      childhood. Delayed gastric emptying (DGE) has been observed frequently in
      association with GER in children. STUDY DESIGN: A retrospective review was
      performed on 1,200 consecutive patients 18 years of age and younger operated upon
      for symptomatic GER or neurologic feeding disorders, or both, at two pediatric
      surgery centers in widely separated geographic areas in the United States of
      America, to compare the results after fundoplication with or without a gastric
      emptying procedure (GEP). RESULTS: Operations included gastroesophageal
      fundoplication (GEF) alone (871 patients), GEF plus GEP (286 patients),
      reoperative GEF plus GEP (30 patients), and GEP alone (13 patients). Thus, 27
      percent of the total and 40 percent of the last 494 children with reflux had a
      GEP. Delayed gastric emptying with retention of more than 60 percent of an
      isotope meal appropriate for age at 90 minutes was present in 241 of the 451
      children with reflux studied. Major neurologic disorders were present in 219 (25
      percent) of 871 children who underwent GEF alone and in 247 (75 percent) of 329
      children who had a GEP. All patients operated upon from both hospitals were
      relieved of recurrent emesis, and those with failure to thrive showed significant
      weight gain; pulmonary symptoms were relieved in 94 percent. Recurrent GER
      developed in 47 (5.2 percent) of 901 children who had GEF alone, but in only four
      (1.2 percent) of 329 patients who had a GEP. CONCLUSIONS: The excellent clinical
      results with low morbidity in this largest reported clinical experience with GEP
      in childhood suggest that a GEP should be combined with GEF for symptomatic
      children who have both GER and DGE. Minimal investigative studies are necessary
      for most neurologically impaired children who require a feeding gastrostomy.

PMID- 7719550
TI  - Peripheral ports are a new option for central venous access.
AB  - BACKGROUND: Peripheral ports represent a new option for central venous access
      that have a low complication rate while providing long duration. This study
      provides five years of evaluation of this device. STUDY DESIGN: All patients had
      follow-up evaluation concurrently, with detailed information collected for the
      first 70 patients. Data were maintained by a nurse specialist team with periodic
      questionnaires sent to treating physicians for follow-up information. Port
      duration, complications, ease of placement, patient and staff acceptance, and
      comparative costs were evaluated. Methods of placement evolved during the past
      five years and culminated in the described approach. RESULTS: One hundred forty
      ports were evaluated. The mean duration was 343 days, with 45 ports in place
      longer than one year. The median port duration in patients without acquired
      immunodeficiency syndrome was 950 days. The overall complication rate was
      1.76/1,000 days. The infection rate was very low at 0.32/1,000 days, and the rate
      of phlebitis was 0.16/1,000 days. Only 9 percent of the ports were removed for
      complications, which included infection and thrombosis. Because of the ease of
      insertion, 80 percent of the ports are placed outside the hospital, allowing for
      cost savings when compared with central ports. CONCLUSIONS: Peripheral ports as a
      means of central venous access have been highly successful in our experience.
      These devices have been very well accepted by the patients and nursing staff.

PMID- 7719553
TI  - The anterior operative approach to the cervical vertebral artery.
AB  - BACKGROUND: Vertebral arterial trauma continues to be a perplexing diagnostic and
      therapeutic challenge. Operative management is often required despite improved
      radiologic interventions for these injuries. Accounts of the operative approaches
      to anterior cervical vertebral artery injuries have been limited. STUDY DESIGN:
      We reviewed our experience with anterior cervical vertebral arterial trauma in 53
      consecutive patients requiring operative management during a 14-year period. In
      seven patients, the vertebral arterial injury was identified at urgent surgical
      intervention either for an expanded cervical hematoma or active bleeding. The
      remaining injuries were identified by arteriographic investigation of penetrating
      cervical trauma. The injuries were equally distributed between the three anatomic
      zones of the anterior cervical vertebral artery. The general features of the
      operative approaches that were used to manage these injuries were the emphasis of
      the study. RESULTS: The anterior approaches to patients with vertical arterial
      trauma were effective in controlling injuries in all cases. Proximal and distal
      ligation of the artery adjacent to the injury site was accomplished in 95 percent
      of the patients. Associated major cervical injuries in 43 percent of the patients
      (carotid artery, eight patients; pharyngoesophageal, six patients; and
      neurologic, nine patients) contributed to the postoperative morbidity rate and
      the overall mortality rate of 10 percent. CONCLUSIONS: The surgeon approaching
      vertebral arterial trauma should have a clear appreciation of the deep anterior
      cervical anatomy to expedite the operative management and avoid unnecessary
      complications related to a misdirected surgical dissection. The descriptions of
      the operative techniques used in this clinical experience can aid the surgeon in
      managing patients with vertebral vascular trauma.

PMID- 7719551
TI  - Delayed postoperative emptying after esophageal resection is dependent on the
      size of the gastric substitute.
AB  - BACKGROUND: Delayed emptying of the gastric substitute is a common problem after
      resection and reconstruction of the esophagus. The occurrence of postoperative
      delayed gastric emptying in patients undergoing resection and reconstruction of
      the esophagus was studied with regard to the type and size of gastric substitute
      and the execution of a pyloroplasty. STUDY DESIGN: From 1983 to 1994, one hundred
      fifty-five patients underwent resection of the esophagus, with a hospital
      mortality rate of 7 percent. The inability to resume a diet of solid food within
      one week after a normal esophagography was defined as delayed gastric emptying.
      One hundred forty patients were studied; group 1, substitution with whole stomach
      with (1a, n = 9) and without (1b, n = 31) pyloroplasty; group 2, substitution
      with distal two-thirds stomach with (2a, n = 20) or without (2b, n = 45)
      pyloroplasty; and group 3, tubulized stomach without pyloroplasty (n = 35).
      RESULTS: Delayed gastric emptying was seen in 38 percent (15 of 40) of patients
      in group 1 (1a, 44 percent; 1b, 37 percent), in 14 percent (nine of 65) of
      patients in group 2 (1a, 10 percent; 2b, 15 percent), and in 3 percent (one of
      35) of patients in group 3. The differences between patients in group 1 and group
      2, and between patients in group 1 and group 3 were significantly different (p <
      0.05). CONCLUSIONS: The type of gastric remnant used for reconstruction is an
      important determinant of postoperative gastric emptying. Pyloroplasty does not
      prevent delayed gastric emptying after esophageal substitution.

PMID- 7719552
TI  - An institutional review of sarcomas of the large and small intestine.
AB  - BACKGROUND: This study was done to review the institutional experience with the
      treatment of sarcoma of the small or large intestine. STUDY DESIGN: Thirty-nine
      patients admitted between the years 1959 and 1987, with a diagnosis of sarcoma of
      the small or large bowel form the basis of this review. RESULTS: At referral, 74
      percent of the patients presented with peritoneal sarcomatosis. Only six patients
      underwent complete resection. The overall five-year survival rate was 20 percent.
      Patients with low grade tumors had median and five-year survival rates of 33.3
      months and 44 percent, respectively, while patients with high grade tumors had
      median and five-year survival rates of 22.4 months and zero percent,
      respectively, p = 0.01. Patients undergoing complete resection had a median
      survival period of 33.3 months, while patients receiving less than complete
      resection had a median survival period of 15.4 months, p = 0.003. Factors found
      to be significant by multifactorial analysis included tumor size, grade, stage at
      presentation, and invasion of adjacent organs. CONCLUSIONS: Sarcoma of the small
      and large bowel is an uncommon entity. Survival rates are relatively poor.
      Aggressive surgical intervention is the mainstay of therapy.

PMID- 7719554
TI  - What the future may hold for general surgery. A position paper of the American
      Board of Surgery.
AB  - Developments in the specialty of general surgery have never been more important,
      nor have the opportunities for general surgeons been more exciting, than at the
      present. Technologic advances and the expansion of basic knowledge of surgical
      diseases have contributed to this renaissance of the field. It is of utmost
      importance that general surgeons seize the opportunity to participate in the
      education of medical students at all levels in the undergraduate years, seek to
      improve the surgical clerkships, and strive for the optimal learning environment
      for surgical residents. Through these means, the best and the brightest students
      will be attracted to general surgery as a career and will be retained in the
      practice of general surgery upon completion of residency training. Education of
      the student preparing for a nonsurgical career in the fundamental concepts
      underlying surgical therapy must be kept at the forefront of an undergraduate
      surgical curriculum. Integration and coordination of graduate surgical education
      in all of the general surgery-based specialties is an important obligation for
      the future, as knowledge expands in each specialty and the need for more
      specialty-specific education becomes apparent.

PMID- 7719555
TI  - Therapy for gastroesophageal reflux disease: the new kid on the block.

PMID- 7719556
TI  - Cardiopulmonary resuscitation in the intensive care unit.

PMID- 7719557
TI  - How patient referral bias can confuse interpretation of clinical results:
      elective lymph node dissections at the Sydney Melanoma Unit.

PMID- 7719558
TI  - Blood rich gastric tube for intrathoracic esophageal operation.

PMID- 7719559
TI  - Retroperitoneal approach to first lumbar vertebral body.

PMID- 7719560
TI  - Portal vein reconstruction at the hepatic hilus using a left renal vein graft.

PMID- 7719561
TI  - Fibroblast growth factors in operative wound healing.

PMID- 7719562
TI  - Rationale for extended lymphadenectomy in gastrectomy for carcinoma.

PMID- 7719563
TI  - Safety, accuracy, and diagnostic yield of needle localization biopsy of the
      breast performed using local anesthesia.

PMID- 7719565
TI  - [New pathways for nursing. Declaration by leading ministerial nursing personnel
      and the cooperative WHO centers].

PMID- 7719564
TI  - Computer-based screening of patients with HIV/AIDS for clinical-trial
      eligibility.
AB  - OBJECTIVE: To assess the potential effect of a computer-based system on accrual
      to clinical trials, we have developed methodology to identify retrospectively and
      prospectively patients who are eligible or potentially eligible for protocols.
      DESIGN: Retrospective chart abstraction with computer screening of data for
      potential protocol eligibility. SETTING: A county-operated clinic serving human
      immunodeficiency virus (HIV) positive patients with or without acquired immune
      deficiency syndrome (AIDS). PATIENTS: A randomly selected group of 60 patients
      who were HIV-infected, 30 of whom had an AIDS-defining diagnosis. DESIGN: Using a
      computer-based eligibility screening system, for each clinic visit and
      hospitalization, patients were categorized as eligible, potentially eligible, or
      ineligible for each of the 17 protocols active during the 7-month study period.
      Reasons for ineligibility were categorized. RESULTS: None of the patients was
      enrolled on a clinical trial during the 7-month period. Thirteen patients were
      identified as eligible for protocol; three patients were eligible for two
      different protocols; and one patient was eligible for the same protocol during
      two different time intervals. Fifty-four patients were identified as potentially
      eligible for a total of 165 accrual opportunities, but important information,
      such as the result of a required laboratory test, was missing, so that
      eligibility could not be determined unequivocally. Ineligibility for protocol was
      determined in 414 (35%) potential opportunities based only on conditions that
      were amenable to modification, such as the use of concurrent medications; 194
      (17%) failed only laboratory tests or subjective determinations not routinely
      performed; and 346 (29%) failed only routine laboratory tests. CONCLUSIONS: There
      are substantial numbers of eligible and potentially eligible patients who are not
      enrolled or evaluated for enrollment in prospective clinical trials. Computer
      based eligibility screening when coupled with a computer-based medical record
      offers the potential to identify patients eligible or potentially eligible for
      clinical trial, to assist in the selection of protocol eligibility criteria, and
      to make accrual estimates.

PMID- 7719566
TI  - [Computer-assisted personnel- and service planning. 1. Results of a study of
      computer use in Hessian hospitals].

PMID- 7719567
TI  - [Buying a computer, but carefully. Tips on selection of techniques and
      counseling].

PMID- 7719568
TI  - [Protection of data in the hospital. The necessity to protect medical data].

PMID- 7719569
TI  - [A new challenge for nurses. Interview with Marita Bauer on the realization of
      nursing insurance legislation].

PMID- 7719570
TI  - [Elizabeth of Thuringia--the duchess in a rag dress].

PMID- 7719571
TI  - [Spots on the pants. Right to damages during a visit to a patient].

PMID- 7719572
TI  - [From a cheap mass product to a comfortable patient gown].

PMID- 7719573
TI  - [Nursing standards. Examples for the creation of median standards, III].

PMID- 7719574
TI  - [Functional brain disorders in old age. The use of nootropic therapeutic
      substances].

PMID- 7719575
TI  - [Many paths lead to the target. Care of the demented--experiences from a stage in
      Hamburg].

PMID- 7719577
TI  - Linking audit and education.

PMID- 7719576
TI  - Update on Raynaud's phenomenon.

PMID- 7719578
TI  - Induction of labour--not how but why?
AB  - Induction of labour is one of the most frequently employed interventions in
      obstetric practice. Despite this, controversy exists over its role in many
      clinical situations.

PMID- 7719579
TI  - Postherpetic neuralgia: current concepts and management.
AB  - Postherpetic neuralgia (PHN) is the most feared complication of herpes zoster and
      remains one of the most common and intractable chronic pain disorders. Recent
      evidence has shed some light on the possible mechanisms of pain, and on the
      prophylactic and treatment approaches to PHN. This article reviews the current
      concepts and management of PHN.

PMID- 7719580
TI  - The clinical use of antithrombin concentrate in septicaemia.
AB  - To date no single agent has emerged as the treatment of choice for the management
      of septic shock and it is becoming increasingly clear that in future it will
      prove necessary to combine treatments to provide the optimum therapy. One group
      of agents that should theoretically prove beneficial in sepsis are the protease
      inhibitors, antithrombin being the one most widely investigated to date. This
      article discusses the evidence supporting its use in the treatment of
      septicaemia.

PMID- 7719581
TI  - Pathophysiological basis of burn management.
AB  - Despite increased public awareness of the dangers of fire, burns remain a part of
      everyday life. Most accident departments will see one or more burn victims each
      day and, although not common, major burns still occur. In this and a second
      article we review the pathophysiology of thermal injury and describe the early
      treatment of a major burn victim.

PMID- 7719582
TI  - The role of neurosurgery in the management of posterior fossa stroke.
AB  - With appropriate treatment, most patients with a posterior fossa stroke make a
      good recovery. The majority of patients do not require surgery. A strategy based
      upon clear guidelines for early surgical treatment can reduce potentially
      avoidable mortality and morbidity without exposing other patients to the risk of
      operative complications from unnecessary intervention.

PMID- 7719583
TI  - When the patient becomes the plaintiff.
AB  - Fortunately for most hospital doctors, being sued is still a relatively unique
      experience; as a result most find the process bewildering. This article attempts
      to explain some of the terms and procedures used when a patient seeks recourse to
      lawyers and possibly to the courts.

PMID- 7719584
TI  - A case of latex anaphylaxis.

PMID- 7719585
TI  - 'Lunchbox is where the heart is'!

PMID- 7719586
TI  - Ventilatory difficulty in a patient with a goitre.

PMID- 7719587
TI  - [Dilatation of the cervical canal with Dilapan before induced abortion in the
      first trimester of pregnancy in primigravidas].
AB  - During the period between Oct. 1, 1993 and June 30, 1994 the authors inserted by
      the intracervical route in 32 primogravidae with unwanted pregnancies before
      abortion with pregnancies shorter than 8 weeks a hydrophil dilator Dilapan. After
      12 hours the rod was removed under general anaesthesia and the pregnancy
      terminated by vacuum aspiration. In three instances after Dilapan insertion
      slight haemorrhage occurred which, however, did not call for removal of the rod.
      Apart from slight tenderness in the hypogastrium, similar as during menses, no
      side-effects were observed. In two instances during Dilapan extraction the rod
      was disrupted and the residue had to be removed by means of Kocher's forceps. In
      all patients the dilation of the cervical canal was sufficient for a 6 mm suction
      curette and further dilation of the cervix by means of metal dilators was not
      necessary. On examination after menstruation the patients did not report more
      massive bleeding nor febrile complications or residues. Based on the described
      results, the authors are of the opinion that gradual dilation of the cervix
      before abortion in the first trimester should be part of the procedure and all
      women who must face this situation should be given this opportunity.

PMID- 7719588
TI  - [Cytodiagnosis and premature birth in light of the Bethesda system].
AB  - 1. Evaluation of cytological cervico-vaginal smears by the Bethesda system
      enlisted cytodiagnostics among important laboratory methods which can be used
      also in risk pregnancies. 2. Vaginal cytology makes it possible to test at the
      same time the hormonal situation during pregnancy, which reflects the placental
      function, and to evaluate also the vaginal biocenosis. 3. The authors provided
      evidence that the large number of superficial cells on the cytological smear
      (more than 10%) is associated with low oestriol and pregnandiol levels which are
      warning signs of the approaching termination of pregnancy. 4. By the action of
      microorganisms on the vaginal epithelium typical morphological changes develop in
      the cell nucleus and in the cytoplasm. By polychromatic staining also the causal
      agents of inflammations and infections threatening the mother and foetus are
      apparent. 5. The authors assume that cytological examination and evaluation
      according to the Bethesda system should be included in the complex of antenatal
      examinations also in women without clinical symptoms of premature delivery or
      without signs of vaginal infection.

PMID- 7719589
TI  - [Factors affecting the results of in vitro fertilization--III. The effect of the
      height and properties of the endometrium in the ultrasound image on the
      probability of implantation].
AB  - Ultrasound examination of endometrium thickness and texture (triple-line,
      homogenous, hyperechogenic) did not help us to predict the implantation after
      embryo transfer. However, in patients stimulated with GnRH analogues and hMG the
      endometrium was significantly higher than in patients stimulated with clomiphene
      citrate and hMG. Triple-line endometrium was more common in women stimulated with
      GnRH analogues and hMG than in those stimulated with clomiphene citrate and hMG.

PMID- 7719590
TI  - [Sexuality in women after treatment of malignant genital tumors].
AB  - Using a structured interview and four questionnaires (Heterosexual development of
      woman, Sexual activity of woman, Sexual function of woman and questionnaire N5
      which is used to evaluate the prevalence and intensity of neurotic symptoms, the
      authors examined 163 women after treatment of a malignant tumour of the
      genitalia. The examination was made during balneological therapy in a spa. Their
      age varied between 20 and 63 years. The feeling of female inferiority was
      recorded roughly in every eighth proband. Deterioration of sexual function of
      varying extent affected every second patient. Changes in emotional relations
      between couples (partners) were more favourable than in sexual life. As regards
      emotional and sexual relations improvement was recorded in every fifth and 11th
      woman resp., as compared with the state before the illness. Husbands or partners
      of the patients had great understanding and were very tolerant. In the authors'
      opinion it is a pleasant surprise that one quarter of the patients perceived the
      associated stress only as medium or even small stress. A general change
      (deterioration) of sexual intercourse correlated directly with subjectively
      perceived stress. The investigation revealed also that women treated on account
      of malignant tumours of the genitals on the territory of former Czechoslovakia
      have practically no contacts with specialists in sexual rehabilitation.

PMID- 7719591
TI  - [Prolonged embryo culture in the in vitro fertilization and embryo transfer
      program].

PMID- 7719592
TI  - [Artificial intrauterine insemination with cryogenic donor sperm --initial
      experience with treatment of infertility in a non-government health facility].

PMID- 7719593
TI  - [Validity of CT examination before comprehensive therapy of carcinoma of the
      uterine cervix].

PMID- 7719594
TI  - [On the concept of gynecology and obstetrics as a profession].

PMID- 7719595
TI  - [Maternal mortality in the Czech Republic in 1993].

PMID- 7719596
TI  - [Thromboembolism and disseminated intravascular coagulopathy in maternal
      mortality in the Czech Republic].

PMID- 7719597
TI  - [Present status and perspectives in hormonal substitution therapy in
      postmenopause].

PMID- 7719598
TI  - [Errors and omissions. Case report no. 5].

PMID- 7719599
TI  - [Removal of the uterus and adnexa and use of low-molecular weight heparin].
AB  - Histological changes of ligated vasa ovarica, uterina, plica lata, mesosalpinx,
      mesovarium etc. were studied in 30 women. Thrombus formation, damage of the
      vessel wall, endothelial cell and tissue bleeding was observed after 30 min. We
      resected the ligated stumps during the operation, before operation an injection
      of LMWH was given. No complete, typical occlusive thrombi developed near the
      ligature. In 3 cases we found evidence of parietal thrombus formation made up of
      platelets in the art. uterina (10.0%) and in 4 cases in veins, and in a few cases
      fibrin was present (13.3%). These changes were found in the same number in the
      vasa ovarica. LMWH reduced the vascular, endothelial damage and the incidence of
      tissue bleeding. Clinical gynecological experience suggests their safety and
      effectiveness in thromboprophylaxis. The rapid and direct obliteration of the
      vascular lumen is due to proliferation of tissue fibroblasts and muscle cells, no
      bleeding occurred after demarcation of the distal stumps and. LMWH significantly
      reduces intravasal changes by important intraoperative reactions against
      thromboplastin generation and haemostasis and can completely replace standard
      heparin in gynecological prophylaxis.

PMID- 7719600
TI  - Irreversible muscle contracture after functioning free muscle transplantation
      using the ipsilateral facial nerve for reinnervation.
AB  - Four patients who underwent functioning free muscle transplantation (FFMT) for
      facial reconstruction developed a progressive disfiguring muscle contracture.
      This complication has not been previously reported. Three of the patients had
      longstanding facial paralysis and were reanimated by FFMT. The fourth patient had
      left hemifacial atrophy but without facial paralysis. She also underwent FFMT for
      augmentation. All four FFMTs were innervated by the ipsilateral facial nerve.
      Initially, they all had a normal facial appearance at rest during the first few
      months after FFMT. However, they all developed a progressive severe muscle
      contracture from 6 to 12 months after FFMT. Continuous spontaneous electrical
      impulse activity, which stimulated the transferred muscle day and night, may be
      responsible for the progressive muscle contracture. From the patients' reported
      sensations and from clinical evaluation, which included a local xylocaine
      injection test, over-reinnervation with a synkinesis effect of the transferred
      muscle is hypothetically the main cause, not over-tension of the muscle itself.
      This complication may possibly be avoided by limiting or decreasing the number of
      fascicles from the ipsilateral facial nerve or better by using a cross-facial
      nerve graft instead of the ipsilateral facial nerve as the innervating motor
      nerve. The outcome with a cross-facial nerve is likely to be more predictable and
      reliable.

PMID- 7719601
TI  - Free intrathoracic jejunal transfer for thoracic oesophageal reconstruction: a
      case report.
AB  - We report the case of a 67-year-old man who had resection of a thoracic
      oesophageal cancer and intrathoracic reconstruction of the oesophagus with a free
      jejunal transfer. The jejunal vessels were anastomosed to an internal thoracic
      artery and vein. The technical and functional results were good.

PMID- 7719603
TI  - The distally based peroneal island flap.
AB  - A distally based island septocutaneous flap supplied by distal perforators of the
      peroneal vessels is described for repair of soft tissue defects of the lower
      third of the leg. The flap can be rotated up to 180 degrees on the axis of the
      pedicle vessels. A series of 10 patients is presented. 7 had uneventful
      reconstructions, 2 had partial necrosis of the tip of the flap but reconstruction
      was satisfactory, and one had necrosis of the distal third of the flap resulting
      in a recurrent leg ulcer.

PMID- 7719602
TI  - Near infra-red spectroscopy: a non-invasive monitor of perfusion and oxygenation
      within the microcirculation of limbs and flaps.
AB  - Reliable early detection of adverse circulatory changes within a flap following
      free tissue transfer and early re-exploration are vital to minimise flap failure.
      Most surgeons rely on clinical assessment to monitor these changes but techniques
      such as plethysmography and laser Doppler have their advocates. These methods are
      limited however to measuring changes close to the surface. Near infra-red
      spectroscopy (NIRS) is a relatively new, non-invasive technique which allows
      continuous monitoring of concentration changes in oxy-, deoxy- and total
      haemoglobin (HbO2, Hb and HbT), as well as oxidised cytochrome aa3, through
      tissue up to 10 cm in depth. Information is provided on tissue oxygen supply,
      cellular oxygen utilisation, blood volume and perfusion status. A study has been
      performed in 10 rabbit hind limbs to assess the ability of NIRS to detect and
      distinguish between venous, arterial and total vascular occlusion. Clear patterns
      of change have been identified which allow rapid detection of vascular occlusion
      with accurate prediction of site. Arterial occlusions were characterised by an
      increase in Hb with a corresponding decrease in HbO2 and HbT. Venous occlusions
      resulted in an increase in HbT with relatively minor fluctuations in Hb and HbO2.
      Simultaneous occlusion of both artery and vein produced similar changes to those
      of arterial occlusion except that HbT decreased only minimally. These findings
      suggest that NIRS has a potentially useful role in the monitoring of free flaps,
      with the great advantage that perfusion can be measured to a considerable depth
      and information provided on the oxygenation profiles both accurately and non
      invasively.

PMID- 7719604
TI  - The radial forearm-lateral arm mega free flap.

PMID- 7719605
TI  - Ear reduction.
AB  - Four cases of ear reduction for congenital macrotia and ear asymmetry are
      presented. To minimize the visible scarring the technique of helical advancement
      was used. The indications for this uncommon procedure are discussed with a review
      of the literature. This simple technique has been effective in achieving the
      desired reduction, leaving the scar hidden in the eaves of the helix, and we
      endorse its wider use.

PMID- 7719606
TI  - The thin tube pedicle: a valuable technique in auricular reconstruction after
      trauma.
AB  - We describe a three staged method of reconstruction for partial helical rim
      defects using a thin post auricular tube pedicle. The technique is illustrated by
      three case reports.

PMID- 7719607
TI  - Epithelioid sarcoma masquerading as Dupuytren's disease.
AB  - Epithelioid sarcoma is a rare and deceptive lesion, often confused both
      clinically and on histopathological examination with other malignant processes.
      The surgical course of two patients with initial diagnoses of Dupuytren's disease
      is described. Early biopsy of all unusual fibrotic lesions on the palm is
      recommended. An aggressive surgical approach to confirmed malignancy is
      mandatory.

PMID- 7719608
TI  - Keloid formation after surgery for release of polysyndactyly of the feet in a
      child.
AB  - Keloid formation on the hands and the feet is very rare but should always be
      anticipated as a possible complication after surgery. Failure to recognise the
      potential for keloid may result in a severe deformity that is functionally and
      cosmetically undesirable. We report severe keloid formation after simple release
      of polysyndactyly of the feet of a 2-year-old child.

PMID- 7719609
TI  - Association between keloids and Dupuytren's disease: case report.

PMID- 7719610
TI  - Mammography and breast implants.
AB  - Mammography in the presence of breast implants is complicated by the opacity of
      the implants, the displacement of breast tissue by the implant, and the presence
      of secondary changes such as calcification within a fibrous capsule. A special
      technique of mammography, known as the displacement technique, has been developed
      by Eklund in the USA, where it is widely used. The displacement technique of X
      ray mammography has been shown to provide superior results to the standard
      compression method. We conducted a telephone survey of 23 mammography units in
      order to assess mammographic practice in the United Kingdom for the patient with
      breast implants. We found a wide variation in practice. There was a general lack
      of awareness of the displacement technique and of its advantages. Only 4
      mammography units in our sample (17.4%) used the displacement technique.

PMID- 7719611
TI  - Triple nostrils associated with cleft lip and palate.

PMID- 7719612
TI  - Historical snippet.

PMID- 7719613
TI  - The seven flap-plasty.

PMID- 7719614
TI  - Musculomucosal nasolabial island flaps for floor of mouth reconstruction.
AB  - A modification of the musculomucosal nasolabial island flap based on the facial
      artery for reconstruction of anterior floor of mouth defects is presented.
      Surgical technique and advantages in comparison to conventional nasolabial flaps
      are described. A series of 14 flaps in 8 patients is presented.

PMID- 7719615
TI  - Nicotinic acetylcholine receptor: structure, function and main immunogenic
      region.

PMID- 7719616
TI  - Aetiological factors in development of myasthenia gravis.

PMID- 7719617
TI  - Idiotypes in myasthenia gravis.

PMID- 7719618
TI  - Molecular and structural characterization of anti-acetylcholine receptor
      antibodies in experimental autoimmune myasthenia gravis.

PMID- 7719619
TI  - Examination of characteristics that may distinguish disease-causing from benign
      AChR-reactive antibodies in experimental autoimmune myasthenia gravis.
AB  - In summary, the strategies of the experimentation described above were designed
      to address the confusion resulting from observations concerning the lack of
      correlation between antibody titers and disease severity in MG patients. Lessons
      learned from these studies of EAMG suggest that if the proportion of the total
      expressed/produced anti-AChR antibody repertoire with disease-causing potential
      differs from patient-to-patient with MG, then assessment of the total antibody
      titer becomes meaningless unless a particular patient produces disease-causing
      reactivities that make up a major portion of the total titer. Not only may
      disease severity depend on the titer of a small subset of disease-causing
      antibody(s) reactive with a particular conformation-dependent AChR region, but
      may also depend on the relative contribution of additional subsets of antibody
      with functionally irrelevant or potentially protective activity. The key to
      exploiting the existence of antibody subsets with differing disease-causing
      potential will be to create probes that would allow the easy monitoring of the
      relevant reactivities. For instance, carefully selected anti-idiotypic antibodies
      (such as the 11E10 monoclonal antibody described above) may be of great value
      when specifically capable of recognizing idiotypes that are selectively
      associated with disease-causing anti-AChR antibodies and under-represented on
      antibodies lacking disease-causing capability. If, in addition, characteristics
      of helper T cells are identified that allow more accurate prediction of D+ Id
      production, exciting opportunities would become available to more directly
      evaluate disease mechanisms and to develop more highly efficacious
      immunotherapeutic strategies.

PMID- 7719620
TI  - Single-scan in vivo lactate editing with complete lipid and water suppression by
      selective multiple-quantum-coherence transfer (Sel-MQC) with application to
      tumors.
AB  - A novel single-scan selective homonuclear multiple-quantum coherence-transfer
      technique, Sel-MQC, is presented that achieves lactate editing with complete
      lipid and water suppression. The method is suitable for studying tissues with
      high fat content and those subject to substantial motion. Frequency-selective
      excitation is employed to selectively prepare lactate into its multiple-quantum
      states; lipid and water are left in the single-quantum modes and eliminated by
      the multiple-quantum selection gradients. The efficiency of lipid suppression is
      monitored by a 2D Sel-MQC experiment which separates lipid and lactate along the
      multiple-quantum-evolution dimension. The spatial distribution of lactate can be
      imaged by the spectroscopic imaging version of Sel-MQC. Sel-MQC sequences were
      demonstrated both in phantoms and in vivo, using subcutaneously implanted murine
      EMT6 tumors.

PMID- 7719621
TI  - 31P NMR kinetics study of cardiac metabolism under mild hypoxia.
AB  - The effects of mild hypoxia on the metabolic and mechanical functions of
      isovolumic perfused rat hearts have been studied. 31P NMR has been used to follow
      the metabolite concentrations as well as the intracellular pH. Additionally, the
      energy transfer through the creatine kinase reaction was estimated by the
      magnetization-transfer technique. The needs of myofibrillar energy and of
      mitochondrial ATP production have been assessed through mechanical activity and
      oxygen-consumption rate. It has been observed that mild hypoxia simultaneously
      impairs contractile and metabolic functions. The aerobic ATP production is
      maintained under these conditions while anaerobic energy metabolism seems
      accelerated. The accumulation of some metabolites (ADP and P(i)) and the decrease
      of creatine kinase forward flux (Vfor) tend, however, to prove that ATP
      availability for myofibrils is lowered. The large aerobic energy production
      observed must therefore be explained by an energy wastage in the mitochondria. In
      spite of normal ATP concentration, a contractile dysfunction is observed and can
      be explained by the P(i) accumulation, which is known to impair the use of the
      myofibrillar ATP. Another hypothesis supported by the magnetization-transfer
      experiments is the poor ATP availability resulting from the ATP wastage in the
      mitochondria and from the inefficient energy transport by the PCr-Cr shuttle.

PMID- 7719622
TI  - An analysis of the effects of eddy currents on L-band EPR spectra.
AB  - Recently, impressive results have been obtained with EPR studies of living
      animals and perfused organs using low-frequency EPR. In many instances in such
      studies, however, there are apparent distortions of the spectra. The shapes of
      these spectra and theoretical considerations indicate that these effects are due
      to eddy currents in the moderately conductive biological materials. Therefore the
      effects of eddy currents produced in biological samples under typical conditions
      being employed for in vivo EPR studies have been systematically studied in order
      to determine the extent of these effects and to develop methods for compensating
      for these effects. The presence of eddy currents was found to decrease the Q
      factor and distort the shapes of the EPR spectra. The distortion of the spectra
      led to linewidth broadening, changes in peak heights, and shifts of the apparent
      center of the lines. These effects could be corrected instrumentally, but this
      was effective only when signals have a high S/N. The use of appropriate computer
      simulations, based on linear combinations of the expected absorption and
      dispersion signals, can effectively correct for the effects of eddy currents and
      provide accurate data on the parameters of EPR spectra that are needed for most
      or all of the analyses used in biological studies of animals and tissues at low
      frequencies.

PMID- 7719623
TI  - Proton relaxation and spin label studies of papaverine localization in ionic
      micelles.
AB  - The localization of papaverine (PAV) in micelles of zwitter-ionic N-hexadecyl-N,
      N-dimethyl-3-ammonio-1-propanesulfonate (HPS), cationic cetyltrimethylammonium
      chloride (CTAC), and anionic sodium dodecyl sulfate (SDS) in D2O was studied by
      1H NMR and ESR in the presence and absence of 5-doxyl- or 12-doxyl-stearic acid.
      PAV, surfactants, and spin probes are characterized by restricted anisotropic
      motion in micelles. The rotational correlation time of doxyl fragment was in the
      range of 0.2 to 0.5 nanoseconds. Binding of PAV to micelles decreases the
      mobility of both probes, suggesting the localization of PAV inside the
      hydrophobic part of micelles near the micelle-water interface. According to the
      NOE data, the methoxy groups of PAV are located in the vicinity of the nitrogen
      atom in CTAC and HPS micelles, the methoxy groups of the PAV heterocycle being
      immersed slightly deeper inside the micelle. The T1 relaxation enhancements by
      two different spin probes show that the H5 and methoxy substituents of the PAV
      heterocycle are in close proximity to the alpha-CH2 of acyl chains in all types
      of micelles, whereas H3 and H12 are the most distant from the alpha-CH2. No
      significant differences were found for the protonated and neutral PAV in SDS
      micelles at pD 4.9 and 11.2. These data show that the geometry of the PAV-micelle
      complex is practically independent of the PAV charge and surfactant head-group.

PMID- 7719624
TI  - A new localization method using an adiabatic pulse, BIR-4.
AB  - A new method is described for accomplishing localized spectroscopy with an
      adiabatic pulse, BIR-4. The method has advantages similar to previously described
      combinations of outer-volume suppression (OVS) and ISIS, with the additional
      advantages that localization is achieved with only three radiofrequency pulses
      and the localization remains accurate even in the presence of intense signals
      with short relaxation times. This new localization pulse sequence is referred to
      as integrated OVS-ISIS. Computer simulations, experimental images of the
      localized volumes, and in vivo 1H spectroscopy measurements demonstrate the high
      degree of localization achievable with integrated OVS-ISIS.

PMID- 7719625
TI  - 13C-coupled relaxation studies of a leucine zipper peptide using polarization
      transfer pulse sequences.
AB  - Three new pulse sequences are described for perturbing magnetization modes in 13C
      coupled relaxation experiments via polarization-transfer techniques. Relative to
      non-polarization-transfer pulse sequences, these new pulse sequences result in
      carbon NMR spectra with significantly improved signal-to-noise ratios, a
      condition required for coupled relaxation studies of larger biomolecules. These
      pulse sequences are used to study molecular tumbling of a 13C-labeled leucine
      zipper peptide, GCN4-p1, in aqueous solution. Experimental data obtained for the
      AX2 spin system associated with the 13CH2 moiety of the peptide are fitted to the
      Favro diffusion model via nonlinear least-squares minimization. The least-squares
      fits provide values for rotational diffusion coefficients. Diffusion coefficients
      from relaxation studies performed at different temperatures yield enthalpies for
      the diffusional motion. Deficiencies in the fits of the relaxation data suggest
      the need for expanded relaxation models that account for proximate protons in the
      vicinity of the 13CH2 moiety.

PMID- 7719626
TI  - One-shot measurement of spin-lattice relaxation times in the off-resonance
      rotating frame using MR imaging, with application to breast.

PMID- 7719627
TI  - Three methods of calibration in quantitative proton MR spectroscopy.

PMID- 7719628
TI  - Reduction of truncation artifacts in chemical-shift imaging by extended sampling
      using variable repetition time.

PMID- 7719629
TI  - Identification of hydrogen-bonded lysine and arginine residues in a protein by
      means of chi 4-torsional-angle determination.

PMID- 7719630
TI  - Short selective pulses for biochemical applications.

PMID- 7719632
TI  - Molecular cloning and expression of hardening-induced genes in Chlorella vulgaris
      C-27: the most abundant clone encodes a late embryogenesis abundant protein.
AB  - To investigate the effects of hardening on gene expression in Chlorella vulgaris
      Beijerink IAM C-27 (formerly Chlorella ellipsoidea Gerneck IAM C-27), a frost
      hardy strain, 17 cDNA clones corresponding to hardening-induced Chlorella (hiC)
      genes were isolated by differential screening of a cDNA library from 6-h hardened
      cells. Northern blot analysis of transcripts of hiC genes showed that these genes
      are specifically induced by hardening and that their patterns of induction vary.
      Southern blots of genomic DNAs from two strains (Chlorella ellipsoidea Gerneck
      IAM C-102, chilling-sensitive; and C. vulgaris C-27, frost-hardy) of Chlorella
      indicated that ten hiC clones out of 17 hybridized only with DNA of strain C-27
      and the other seven clones hybridized with DNA of both strains. However, of these
      seven clones, transcripts corresponding to six clones did not accumulate in
      strain C-102 at low temperatures. The sequence of a deduced protein encoded by
      the most abundant clone, hiC6, exhibited homology to sequences of Group III LEA
      (late embryogenesis abundant) proteins and had an amino-terminal amino acid
      sequence that was similar to the sequences of chloroplast transit peptides.

PMID- 7719631
TI  - Molecular cloning and characterization of S-adenosyl-L-methionine:scoulerine-9-O
      methyltransferase from cultured cells of Coptis japonica.
AB  - S-Adenosyl-L-methionine:scoulerine-9-O-methyltransferase (SMT) catalyzes the
      transfer of the S-methyl group of S-adenosyl-L-methionine to the 9-hydroxyl group
      of scoulerine during the biosynthesis of berberine. We have isolated functionally
      active cDNA clones (pCJSMTs) from a cDNA library prepared from cultured cells of
      Coptis japonica. The longest cDNA insert (pCJSMT1) had an open reading frame that
      encoded 351 amino acids, but the calculated molecular mass (38,364 Da) of the
      deduced product was slightly lower than the experimentally determined molecular
      mass of purified SMT. Rapid amplification of the 5' end of the cDNA indicated
      that the full-length cDNA of SMT consisted of 1,458 nucleotides that encoded 381
      amino acids. When the full-length cDNA was expressed in E. coli, the molecular
      mass of the expressed SMT was greater than that of native SMT in Coptis cells.
      This result suggests that SMT might be produced in a pre-mature form and
      processed post-translationally. SMT was also found to exhibit sequence homology
      to other O-methyltransferases from plants and N-terminal region of the SMT
      polypeptide appeared to be necessary for enzymatic activity.

PMID- 7719633
TI  - Molecular ecology of infectious diseases.

PMID- 7719634
TI  - The epidemiology of HIV in India.
AB  - India is the first country outside Africa where an HIV-2 epidemic is running in
      parallel to an HIV-1 epidemic, resulting in a significant proportion of double
      infections. HIV is spreading rapidly, mainly by heterosexual contact, but also
      among intravenous drug users. Genetic analyses of the HIV variants circulating in
      India point towards HIV-1 and HIV-2 having been introduced into the country
      recently.

PMID- 7719635
TI  - Recombinant cytokines for controlling mycobacterial infections.
AB  - Knowing how mycobacteria exploit host cytokines to survive and which cytokines
      have important roles in host defense against mycobacteria should allow the use of
      these molecules in the treatment of mycobacterial infections. Both interleukin 2
      and interferon gamma have been used to treat patients with leprosy, and
      granulocyte-macrophage colony-stimulating factor is presently being administered
      to AIDS patients infected with Mycobacterium avium.

PMID- 7719636
TI  - Determinants of cell entry and intracellular survival of Mycobacterium
      tuberculosis.
AB  - The ability of Mycobacterium tuberculosis to sustain a chronic infection and
      cause disease in a subset of those infected depends on its products--virulence
      factors--that enable the organism to enter and survive indefinitely inside
      mononuclear phagocytic cells by subverting cellular antimicrobial mechanisms.
      Characterizing these factors is essential to understanding the pathogenesis of M.
      tuberculosis.

PMID- 7719637
TI  - Polyoma virus middle T antigen: meddler or mimic?
AB  - Polyoma virus middle T antigen duplicates the actions of growth-factor receptors
      in binding the signalling molecules phosphatidylinositol 3'-OH kinase and Shc.
      These properties indicate that middle T is mitogenic and may be required to
      overcome inhibition of DNA replication during the lytic life cycle of the virus.

PMID- 7719638
TI  - Morbilliviruses in marine mammals.
AB  - Two of the three recently discovered aquatic morbilliviruses have been
      responsible for mass mortalities among marine mammals; both affect more than one
      host species, but susceptibility to infection varies considerably between
      species. Apparent differences between the dynamics of aquatic morbilliviruses and
      their terrestrial counterparts may be a consequence of high levels of
      interspecific transmission.

PMID- 7719639
TI  - Having a blast: exploring the pathogenicity of Magnaporthe grisea.
AB  - The rice blast fungus Magnaporthe grisea has an exquisite level of pathogenic
      specialization, allowing it to infect and colonize rice, subvert the metabolism
      of the host and spread to new hosts. Through a combination of cytology and
      molecular-genetic analysis, a picture is gradually emerging of the many
      interlinked processes that are required for successful infection of the plant.

PMID- 7719641
TI  - Unlike its human counterpart, band 3 anion exchange protein from goat erythrocyte
      membrane shows a lack of reactivity against various -SH oxidants and protease
      treatments.
AB  - Studies involving a number of -SH oxidants and proteases were made to analyse the
      organization of band 3 in goat erythrocyte membrane. -SH oxidizing agents such as
      diamide, Cu2+.o-phenanthroline and phenylene dimaleimide, known to cause cross
      linking of human erythrocyte band 3, failed to show any cross-linking in the case
      of goat band 3 protein. When resolved to their individual components using -SH
      reducing agent beta-mercaptoethanol, high molecular weight protein adducts formed
      as a result of diamide treatment did not show any band 3 on two-dimensional
      electrophoresis. Also no proteolysis of band 3 was detected when intact goat
      erythrocytes were exposed to pronase, though marked proteolysis was noticed in
      the case of human band 3 proteins under similar conditions. These studies
      involving -SH oxidant and protease treatments suggest a different organization
      for goat erythrocyte band 3 protein as compared to that of human in erythrocyte
      membrane.

PMID- 7719640
TI  - Comparative studies on NADP(+)-linked malic enzyme in the central nervous system
      of ectothermic and endothermic animals.
AB  - The maximum activity and intracellular distribution of NADP(+)-linked malic
      enzyme in brain of Mammalia, Aves, Reptilia, Amphibia and Pisces are reported.
      Malic enzyme activity was present in all animals brains investigated. Most of the
      enzyme activity was located in the mitochondrial fraction. In brain of
      endothermic animals the activity of malic enzyme was several-fold higher than in
      ectothermic animals. Other NADPH-producing enzymes (i.e. NADP(+)-linked
      isocitrate dehydrogenase and hexosemonophosphate shunt dehydrogenase) activities
      were essentially similar in all animals brains tested. However, the total
      potential capability of NADPH production was lower in ectothermic animals (due
      mainly to lower malic enzyme activity). It is suggested that the presence of
      NADP(+)-linked malic enzyme in the brain may be related mainly to mitochondrial
      metabolism, especially to maintain the mitochondrial pool of NADP+ in reduced
      form.

PMID- 7719642
TI  - Ouabain-insensitive, Na(+)-stimulated ATPase activity in rabbit cardiac
      sarcolemma.
AB  - The rabbit cardiac sarcolemma shows an ouabain, Na,K-stimulated ATPase activity
      and an ouabain-insensitive, Na-stimulated ATPase activity. The Na-ATPase has the
      following characteristics: (i) It is also stimulated by other monovalent cations.
      (ii) It is inhibited by 2 mM Furosemide and by 2 mM ethacrynic acid. (iii) It
      reaches maximal values (Vmax) at around 20 mM Na+. (iv) The apparent Km is around
      5 mM. Except for the monovalent cation stimulation, the main characteristics of
      this ATPase are very similar to those of the ouabain-insensitive, Na-stimulated
      ATPase of mammalian kidneys.

PMID- 7719643
TI  - Markers of T-cell differentiation and maturation in C57BL/6 and BALB/c mice and
      in the calf: a comparative study.
AB  - No significant differences were found between C57BL/6 and BALB/c mice in the
      levels of Thy 1.2 antigen (a T-cell marker) or the activities of the T-cell
      maturation-related enzymes adenosine deaminase (ADA, EC 3.5.4.4), serine-esterase
      (SE, EC 3.4.21), N-acetyl-beta-D-glucosaminidase (NABG, EC 3.2.1.30) and beta
      glucuronidase (BG, EC 3.1.1.1), in either unfractionated lymphoid cells or T
      lymphocyte-enriched fractions. ADA, SE, NABG and BG activities were much higher
      (P < 0.01) in the calf than in the corresponding populations in mice. However,
      the distributions of these activities among thymocyte subpopulations were very
      similar in mice and the calf. These results provide indirect evidence to suggest
      that the course of T-cell maturation is similar in mice and the calf.

PMID- 7719644
TI  - A comparative catabolism study of isoleucine by insect and mammalian tissues.
AB  - The metabolism of [U-14C]isoleucine was examined in different tissues of five
      species of lepidopteran and four species of non-lepidopteran insects. Slices of
      fat body, epidermis, Malpighian tubule, gut, and muscle were incubated in a
      culture medium containing [U-14C]isoleucine; the medium was analyzed by ion
      exclusion LC to quantify labeled metabolites. Tissues of lepidopteran insects
      secrete high levels of metabolites including 2-keto-4-methylvalerate, 2
      methylbutyrate, propionate, and acetate. Tissues of non-lepidopteran insects
      secrete low amounts of these acids. Analysis of isoleucine transaminase activity
      in selected tissues of non-lepidopteran insects indicated that those tested
      contain significant activity. These results demonstrate that tissues of
      lepidopteran insects have a unique ability to secrete short chain acids, derived
      from isoleucine, into the medium. The secretion of propionate correlates with the
      ability to synthesize ethyl-branched juvenile hormones and indicates the presence
      of an efficient transport system for short chain acids. We also monitored the
      secretion of acidic metabolites of isoleucine by different tissues of the rat.
      Muscle was most active in secreting keto acid whereas heart secreted high levels
      of 2-methylbutyrate. Negligible quantities of metabolites of isoleucine were
      secreted by the liver.

PMID- 7719645
TI  - Purification and characterization of HSP70 proteins from Torpedo electric organ.

PMID- 7719646
TI  - Partial purification and kinetic properties of human placental cytosolic
      aspartate transaminase.
AB  - Human placental cytoplasmic aspartate transaminase was purified 404-fold by heat
      treatment, ammonium sulfate fractionation, dialysis and DEAE-Sephadex
      chromatography. The pH optimum of the enzyme was 6.8 in either phosphate or
      cacodylate buffer. The Km values of alpha-ketoglutarate and L-aspartate were 2.06
      and 22.5 mM, respectively. A 78% inhibition of the enzyme was noted at 4 mM
      concentration of maleate which inhibited the enzyme upon competing with alpha
      ketoglutarate with a Ki value of 1.72 mM. The kinetic properties of this enzyme
      are compared with those of the enzyme from various mammalian and other sources.
      The data are discussed in terms of the probable effectiveness of this enzyme in
      catabolizing L-aspartate in placenta especially after the consumption of a high
      protein diet by the pregnant mother.

PMID- 7719647
TI  - Release of sialyltransferases from rat liver Golgi membranes by a cathepsin D
      like proteinase: comparison of the release of Gal beta 1-4GlcNAc alpha 2-6
      sialyltransferase, Gal beta 1-3(4)GlcNAc alpha 2-3 sialyltransferase and
      lactosylceramide alpha 2-3 sialyltransferase (SAT-1).
AB  - The activities of Gal beta 1-3(4)GlcNAc alpha 2-3 sialyltransferase and SAT-1
      were measured in rat liver Golgi in inflammation; both enzymes decreased by about
      50%. This compares with increases of about 3-fold for the Gal beta 1-4GlcNAc
      alpha 2-6 sialyltransferase. All three sialyltransferases were released from
      disrupted Golgi membranes by incubation at reduced pH which activates an
      endogenous cathepsin D which is believed to be the lysosomal enzyme. Pepstatin A
      was found to block the release of all three sialyltransferases providing support
      for the role of cathepsin D as the proteinase that clips the catalytic portions
      of the enzymes from their membrane anchor and stem regions.

PMID- 7719648
TI  - In vitro and in vivo thermal activation of steroid-receptor complexes from rats
      and ground squirrels (Spermophilus citellus).
AB  - Using 3H-labelled triamcinolone acetonide (3HTA, synthetic steroid hormone), it
      was shown that the in vitro time course kinetics of thermal activation of 3HTA
      receptor complexes exhibited the same temperature dependence in liver cytosols
      prepared from hibernating ground squirrels (Spermophilus citellus) as in cytosols
      from the rat. When 3HTA was injected in vivo to animals hibernating with a body
      temperature of 3 degrees C, the activation and nuclear uptake of the in vivo
      formed steroid-receptor complexes proceeded at a slow rate, comparable to the one
      predicted by in vitro studies. In the hibernator, the results are not indicative
      of adaptive modifications at the level of thermal activation, but prove that
      steroid action does proceed at a temperature incompatible with hypothermic
      survival in the nonhibernator.

PMID- 7719649
TI  - [Epidemiologic research in occupational medicine and industrial ecology].
AB  - Complicated nature of present environmental pollution necessitates thorough
      epidemiologic studies to reveal causal and dose-effect relationships between
      ecology and health state of population. Besides that we should consider influence
      of such items as lifestyle (nutrition, psychologic state, bad habits) on public
      health. The article shows role of occupational hazards for health state,
      influence of parents' occupations on health and vitality of the children. The
      authors revealed effects of occupational factors (occupation) on relative risk of
      mortality with some diseases and on total life expectancy.

PMID- 7719650
TI  - [Physiologic and hygienic aspects of work conditions for humans at open
      territories of the Far North].
AB  - The studies proved that males and females, who work outdoors in Far North,
      demonstrate strain of thermoregulation and such associated systems as primarily
      cardiovascular and respiratory ones. Lower tolerance of the workers to physical
      strain shows more intensive impact of work in such regions on physiologic
      functioning. The studies determined peculiarities of pulmonary circulation in the
      inhabitants of Far North. Those peculiarities are caused by cooling and low
      absolute humidity. Functional strain in the examinees appeared to depend on
      weather conditions of Far North.

PMID- 7719651
TI  - [Development of peripheral neurovascular disorders in miners exposed to cool
      microclimate].
AB  - Complete clinical and physiologic examination of 415 tunnelers exposed to
      intensive vibration in cooling microclimate proved that extreme functioning of
      thermoregulation results in shorter development, quicker progression of vibration
      disease and abortive types of the disease. The data obtained were helpful to base
      treatments and prophylaxis including special clothes, appropriate therapy.

PMID- 7719652
TI  - [Characteristics of the serum lipids in workers of lead industry].
AB  - The study covered peculiarities of lipid metabolism in workers engaged into lead
      production. Most the examinees showed reliable increase of total blood
      cholesterol, low and extremely low density lipoproteins cholesterol,
      triglycerides and atherogenic coefficient, combined with decreased high density
      lipoproteins cholesterol. Occupational factor was proved dominant in
      atherosclerosis formation in lead production workers. Those workers demonstrated
      also significant comedown of Apo A-1 amount, reliable increase of Apo B level and
      Apo B/Apo A-1 ratio.

PMID- 7719653
TI  - [Health status of the Russian population and current problems in occupational
      medicine and industrial ecology].
AB  - Major goal of occupational medicine--better health of employees--could be reached
      through integrated theoretical and practical approaches to the issues assigned to
      different scientific spheres. The article suggests some principles of new
      direction in prophylactic medicine. Those principles form a theoretical basis for
      occupational medicine and industrial ecology: being also a powerful instrument
      for evaluation and management of occupational and ecologic risk. The authors
      define group and individual risk, base a concept of residual risk and necessitate
      further improvement of protecting measures to restrict individual risk for every
      employee.

PMID- 7719654
TI  - [Optimization of the indoor air conditioning in the places of excessive radon
      release].
AB  - The experimental modelling covered ventilation and air purification as well as
      air pollution with radon and such derivatives as polonium-218b, lead-214 and
      bismuth-214. The modelling was designed for industrial conditions with higher
      radon release in technologic conversion at enterprises processing uranium. The
      investigators obtained some information to optimize air processing and to lower
      the workers exposure to radon and its derivatives.

PMID- 7719655
TI  - [Correlation between biologic aggression and some physical and chemical
      properties of industrial dust caused by use of friction tools].

PMID- 7719656
TI  - [Occupational morbidity in Russian Federation in 1993].

PMID- 7719657
TI  - [Physiologic and hygienic characteristics of work conditions of miners in the Far
      North].
AB  - Workers engaged into subsurface extraction of sand containing gold were proved to
      work in difficult conditions characterized by stable negative temperatures, high
      concentrations of dust, elevated levels of noise and vibration. The drill
      operators demonstrated extremely unfavorable changes of physiologic processes
      within a shift. Those changes were compromised cardiovascular regulation, early
      occurrence and intensive progress of fatigue. The authors provide recommendations
      to normalize the work conditions and to create rational scheme of work and rest
      for the occupations.

PMID- 7719658
TI  - Selected aspects of the population health status in ecological hazard areas in
      comparison with ecologically "clean" area. II. Assessment of spatial distribution
      of mortality.
AB  - On the basis of age adjusted rates of mortality from all diseases and from
      diseases of the circulatory system in female and male populations living in
      ecological hazard areas and in ecologically "clean" area, the distributions of
      the rate values were assessed. In the regions under consideration, urban and
      rural regions were distinguished. The goodness of fit of the empirical
      distribution to the normal one was assessed using the following statistical
      parameters: arithmetic mean, mode, median, standard deviation, coefficient of
      variation, coefficient of asymmetry, difference between the third and the first
      quartiles, as well as the Chi2 and lambda-Kolmogorow-Smirnow tests, maximum
      difference between cumulative distribution functions and standard deviation of
      differences between empirical and theoretical frequencies. A differentiation in
      the mean values of age adjusted rates of mortality from both groups of diseases
      in ecological hazard areas and in "clean" area was indicated particularly in
      urban female and male populations.

PMID- 7719659
TI  - Some aspects of health problems due to local vibration.
AB  - The development of knowledge of vibration disease during the last century is
      given. Pathogenetic mechanisms, diagnostic methods, clinical classification,
      clinical picture and its stadia and diagnostic difficulties are presented here.
      Measures for its medical treatment and prevention are also described.

PMID- 7719660
TI  - Stress and strain during work among women performing different work tasks.
AB  - This study measured the association between the severity of work in occupations
      performed most frequently by women, workload (as relative aerobic strain and
      heart rate during work) and the reaction to work measured on the basis of changes
      after work in the subjective fatigue rating and working ability. The results
      indicate that there is no rational selection to individual work posts from the
      point of view severity of work and the level of physical working capacity.
      Nevertheless, it has been found that the heart rate during work was dependent on
      the severity of work and not the level of physical working capacity. A decrease
      of working ability after work was more frequent than an increased level of
      fatigue, but the work performed, the level of physical working capacity and the
      relative aerobic strain did not produce any significant differences in these
      parameters. Thus, the data presented above does not confirm the suggestion that
      people with a higher level of physical working capacity can engage a higher
      percentage of VO2max during working time. On the other hand, changes in the
      reaction to work, especially working ability changes, were significantly
      statistically dependent on the heart rate during work. Working ability was
      unquestionably worse when the heart rate during work exceeded 100 beats/min, 50%
      maximal heart rate or 30% heart rate reserve.

PMID- 7719661
TI  - Urinary excretion of copper bound to low molecular weight proteins in the
      population exposed to cadmium in community and occupational environments.
AB  - People living in Cd-polluted areas excrete increased amounts of copper with
      urine. A substantial quantity of this is eliminated with metallothionein the
      concentration of which in urine increases in people exposed to cadmium.
      Therefore, the measurement of metallothionein in urine is applied as a marker of
      renal function in people exposed to cadmium in addition to other low molecular
      weight proteins, beta 2-microglobulins (beta 2MG) and retinol binding proteins
      (RBP). In this study copper bound to metallothionein-like proteins of low
      molecular weight (CuBP)--a newly proposed marker of cadmium nephrotoxicity, as
      well as beta 2MG and RBP, were evaluated in those exposed to cadmium in the
      community and in occupational environments. The results obtained indicated that
      people exposed to cadmium in both polluted environments excreted greater amount
      of CuBP in urine than people not exposed to cadmium. In groups excreting cadmium
      in urine in amounts ranging from 1 to 10 micrograms/l the urinary level of CuBP
      was closely associated with the levels of beta 2MG and RBP. A considerable
      increase in the excretion of urinary CuBP began when Cd concentration in urine
      exceeded 4 micrograms/l. The amount of CuBP excreted was higher in people with
      renal disfunction than in those with a normal renal function. It is suggested
      that urinary excretion of CuBP may be considered as a specific marker of renal
      function in people exposed to cadmium.

PMID- 7719662
TI  - Biological markers of oxidative stress induced by ethanol and iron overload in
      rat.
AB  - Studies on rats treated for 15 months with ethanol (10%, w/v, solution in
      drinking water) revealed that the stimulation of hepatic cytochrome P-450
      monooxygenases activity was accompanied by enhanced microsomal malondialdehyde
      formation, a lipid peroxidation index and a decreased level of the antioxidant,
      alpha-tocopherol. The other components of the prooxidant/antioxidant system,
      diene conjugates and catalase, glutathione peroxidase and superoxide dismutase
      activities were unaffected. Oxidative stress in blood was shown by a significant
      decrease in the alpha-tocopherol level whereas lipid peroxidation and antioxidant
      enzyme activity remained unchanged. The prooxidative effect of ethanol was
      catalytically promoted by an iron overload (Fe-saccharate, 100 mg Fe3+/kg body
      wt. intraperitoneally, 2, 5 and 7 day before test) to simulate the effect of
      alcoholic hemochromatosis. Thus, the level of malondialdehyde and alpha
      tocopherol in the serum may be recommended as biological markers of ethanol
      provoked oxidative stress, which is especially useful in the evaluation of the
      combined effect of ethanol and other chemicals that affect the redistribution of
      active iron complexes.

PMID- 7719663
TI  - Assessment of the effect of n-butanol given to female rats in drinking water on
      fertility and prenatal development of their offspring.
AB  - Female rats were given aqueous solutions of n-butanol containing 0.24, 0.8 and 4%
      n-butanol (0.3; 1.0 and 5.0 g/kg/day) for 8 weeks before and during gestation.
      The control animals received tap water. The experiment was performed in two
      stages. The first comprised of the assessment of the oestrous cycle before
      exposure and then during 4-5 and 7-8 weeks of exposure, and the second stage of
      the fertility of female rats and their foetal development. The duration of the
      cycle and its individual stages in the control and the exposed females were
      similar. It was found that n-butanol alcohol is a foetotoxic agent and produces
      developmental anomalies in a foetus's skeleton and central nervous system.

PMID- 7719664
TI  - Study of the mechanism of todralazine antimutagenic activity: the effect upon
      mutagenicity of daunorubicine.
AB  - Todralazine markedly reduced the mutagenic activity of the standard direct-acting
      mutagen--daunorobicine (DRC)--in the Ames test. Spectrophotometric measurements
      proved that todralazine did not interact with DRC in water solution. Todralazine
      neither interacted with calf thymus DNS in vitro, nor changed the interaction of
      DRC with DNA. Therefore we concluded that the decrease of DRC mutagenicity
      observed in the Ames test should be explained rather in terms of a
      bioantimutagenic than a desmutagenic activity of todralazine.

PMID- 7719666
TI  - Occupational medicine in Polish journals of 1993; part 3.

PMID- 7719665
TI  - Occupational exposure to coal tar pitch volatiles, benzo/a/pyrene and dust in
      tyre production.
AB  - Occupational exposure to coal tar pitch volatiles (CTPVs), benzo/a/pyrene (BaP)
      and dust was evaluated by means of individual measurements carried out in 80
      workers and by stationary measurements on 16 work-posts in two divisions of the
      tyre producing plant. Dust and coal tar pitch volatiles concentrations in the air
      were determinated by the gravimetric method, measured, in the case of CPTVs,
      benzene-soluble fraction (BSF) with ultrasonic extraction. Benzo/a/pyrene
      analysis was performed using high performance liquid chromato-graphy (HPLC) with
      a spectrofluorimetric detector. It was found that nearly all personal sampling
      results for BaP were within the range < 4 divided by 142 ng/m3, except for the
      exposure of workers employed at weighing the raw materials (3,470-6,060 ng/m3) in
      the Semiproducts Division. Attention should be paid to the recorded CTPVs
      concentrations (benzene solubles). About 56% of the Vulcanizing Division workers
      and about 90% of the Semiproducts Division workers were exposed to these
      substances at concentrations of over 0.2 mg/m3 (hygienic standard for benzene
      solubles in USA). Exposure to dust (of high respirable fraction percentage > 90%)
      which exceeded the admissible value (4 mg/m3) was found mainly only in the
      workers of the Semiproducts Division at some work-posts.

PMID- 7719667
TI  - Occupational medicine in the East European journals of 1993; part 3.

PMID- 7719668
TI  - Clinical indicators as a stimulus to QA in hospitals an early report.
AB  - To increase medical staff involvement in hospital quality assurance activities
      and to increase the clinical component of a hospital accreditation process, the
      Australian Council on Health Standards (ACHS) through its Care Evaluation Program
      (CEP) has combined with the Medical Colleges, which are the professional
      associations for surgeons, internists, etc. Objective measures of care (clinical
      indicators) have been developed, and the first set (Hospital Wide Medical
      Indicators--HWMIs) was introduced into the Accreditation process from January
      1993. Both quantitative and qualitative information is being received back by the
      Care Evaluation Program. The latter information reveals that the indicators have
      stimulated an increase in QA in hospitals.

PMID- 7719669
TI  - How case management can improve the quality of patient care.
AB  - In January 1993, The New York Hospital Medical Center of Queens, a 487 bed acute
      care teaching hospital, created a Case Management Department to provide quality
      health care for patients that was cost efficient and at the same time reduce
      length of stay. Registered nurses with extensive medical and surgical expertise
      who were quality assurance/utilization coordinators and discharge planning nurses
      were cross-educated to become patient case managers. The case manager coordinates
      patients care services to improve the quality of the total patient experience.
      Reviews are conducted daily. The case managers indicate quality issues on their
      computer worksheets. Quality concerns are addressed and referrals made to the QA
      Department. Case Management Team rounds are conducted on the patient unit to
      discuss quality issues and barriers to discharge. Many delays were noted in
      patient care services i.e. Physical Therapy (P.T.) and Radiology. Readmissions
      within 48 hours of discharge were noted and reviewed as an indicator to monitor
      outcome and quality concerns. Continuous Quality Improvement (CQI) projects were
      initiated to reduce patient care delays. Multidisciplinary teams were formed to
      expedite solutions. The number of P.T. and Radiology delays were dramatically
      reduced through the CQI process. The case manager's role is vital to the delivery
      of quality patient care and containment of ever spiraling health care costs.

PMID- 7719670
TI  - How many days of hospitalization for an appendectomy?
AB  - The length of stay (LOS) of a surgical procedure is influenced both by the real
      need for medical and nursing care of the patient and also by the practice style
      of each unit, which can include unjustified stays. The aim of this work was to
      estimate the appropriate LOS for appendectomy and its differences with the LOS
      observed in practice. Two hundred and forty-nine medical records (249 admission
      days and 1447 successive stays) for patients over 6 years old who had had an
      appendectomy in 1992 were classified by Diagnosis Related Groups (DRG) and
      reviewed using the Appropriateness Evaluation Protocol. 1.6% of admission days
      and 31.7% of successive stays were assessed inappropriate. The appropriate LOS
      for appendectomy was 4.7 days as opposed to 6.8 days of observed LOS. For the DRG
      167 (76.3% of the sample) appropriate LOS was 3.4 days (observed LOS 4.9 days).
      These results suggest the existence of an important proportion of avoidable
      hospital stays and provides a simple and low cost methodology for assessing the
      suitability of local hospitalization practices.

PMID- 7719671
TI  - Keeping the customer satisfied: issues in the interpretation and use of patient
      satisfaction surveys.
AB  - Patient satisfaction and customer focus are increasingly important objectives set
      for health services. The patient satisfaction survey is becoming the main method
      of assessing this aspect of health care. In competitive environments, those
      institutions that show that they respond to consumers' needs are in a better
      position to attract funding. The use of patient satisfaction surveys in quality
      assurance-type activities is also increasing. In these contexts, however, the way
      in which patient satisfaction surveys should be interpreted and used to maximise
      the satisfaction of patients has received little critical attention. Problems in
      interpreting the results of satisfaction surveys arise from the weak conceptual
      foundation of patient satisfaction, which has been well documented in the
      literature. The objective of this paper is to show that using current
      formulations of patient satisfaction surveys in quality assurance-type activities
      and competitive environments may not lead to the maximisation of patients'
      satisfaction with health services. If the satisfaction of patients is to be
      maximised then it is necessary to extend the current conceptual basis of patient
      satisfaction to recognise explicitly the decision-making contexts in which the
      results will be used. This paper identifies the manner by which this extension
      should occur by considering some of the problems and pitfalls of interpreting and
      using the results of surveys to maximise patients' satisfaction.

PMID- 7719672
TI  - Patient satisfaction with nursing care, evaluation before and after cutback in
      expenditure and intervention at a surgical clinic.
AB  - After a major cutback in the budget and staffing of a surgical clinic in southern
      Sweden there was intervention to improve the quality of nursing care and to
      evaluate the outcome. The intervention consisted of the implementation of: (1)
      nursing care organized in such a way that it would secure continuity of the nurse
      patient relationship, (2) individually planned care by means of diagnostic
      reasoning, and (3) quality assurance for aspects believed to be connected with
      quality of care. Patient satisfaction before and after the intervention was
      assessed by means of a patient questionnaire survey (May 1991; n = 105 and May
      1992; n = 137). Patient satisfaction improved significantly in variables related
      to nursing care viz. overall satisfaction and satisfaction with information and
      decision making; satisfaction with contact and staff-patient relationship; ward
      facilities and physical treatment or examinations; and satisfaction with physical
      nursing care. The results were interpreted to mean that the intervention may have
      counteracted any negative impact the reduced budget might have had such as the
      higher patient turn-over and the shorter in-patient periods, and thus seemed to
      have improved the quality of the nursing care in terms of patient satisfaction.

PMID- 7719673
TI  - Doctor-shopping in Hong Kong: implications for quality of care.
AB  - Doctor-shopping is defined as the changing of doctors without professional
      referral in the same illness episode. Two surveys on samples of patients
      attending Government Out-Patient Departments (GOPDs) in Hong Kong in 1989 (n =
      869) and 1990 (n = 901) estimated the prevalence of shopping at nearly 40%, the
      main reason being a persistence of symptoms. Doctor-shoppers were likely to be
      younger with higher expectations of health care and who expressed dissatisfaction
      about aspects of the present service. In Hong Kong, patients perceive western
      medicine to be more effective and have high expectations of the effects of
      western drugs, in particular, in their administration by injection. Patients
      should be warned about iatrogenic health risks incurred from doctor-shopping;
      health education programmes are needed to modify unrealistic views about quality
      care. Health care providers in a mixed care system should promote greater
      continuity of care between doctors and both the public and private sectors, and
      identify and resolve problems which may be responsible for discontinuity of care.

PMID- 7719674
TI  - Development of patient satisfaction surveys in the Czech Republic: a new approach
      to an old theme.
AB  - Although patient satisfaction surveys have become well established features of
      Western healthcare systems, free expression was suppressed for much of the past
      50 years in the Czech Republic. As part of a quality assurance program
      established at the University Hospital Kralovske Vinohrady in Prague, and under
      the direction of a sociologist, a patient satisfaction pilot study was instituted
      as a precursor to a broader and ongoing survey. A cohort of 150 patients who were
      discharged following hospitalization on one of three medical or surgical services
      were given the opportunity to respond to a 36 item questionnaire devised as a
      result of study of similar instruments, 101 completed the questionnaire. Patients
      who responded were comparable to those hospitalized on these services, and other
      factors, demographic and otherwise, were likewise comparable. Once the concerns
      regarding the opportunity for free expression were addressed, it was found that
      interpersonal interactions with physicians, nurses, and other healthcare
      personnel provided the greatest satisfaction for patients and greatly exceeded
      amenities such as the quality of the hospital room and food. As a result of this
      pilot study, a subsequent survey of more than 500 patients has begun. It is
      believed that such surveys will provide useful data for quality assurance as well
      as involving patients in an assessment of the care provided.

PMID- 7719675
TI  - Calculation and administration of drug dosage by Swedish nurses, student nurses
      and physicians.
AB  - A diagnostic test was used to assess the mathematical knowledge and skills in 545
      experienced nurses and 197 student nurses. The main purpose of this study was to
      investigate if student nurses and registered nurses have adequate knowledge and
      skills in drug dosage calculation. Nine out of fourteen test items were solved
      accurately and no differences were found in the average performance between the
      two groups. To evaluate physicians' knowledge about statutory regulations on drug
      prescription and legal responsibility, 36 physicians from different health care
      areas answered a questionnaire. The answers revealed that the majority was not
      familiar with these regulations. The results are discussed in relation to nurse
      education and the physicians' legal responsibility in connection with drug
      administration and prescription.

PMID- 7719676
TI  - Low-dose computed tomographic imaging in orbital trauma.
AB  - We review the findings in 75 computed tomographic (CT) examinations of 66
      patients with orbital trauma who were imaged using a low-radiation-dose CT
      technique. Imaging was performed using a dynamic scan mode and exposure factors
      of 120 kVp and 80 mAs resulting in a skin dose of 11 mGy with an effective dose
      equivalent of 0.22 mSv. Image quality was diagnostic in all cases and excellent
      in 73 examinations. Soft-tissue abnormalities within the orbit including muscle
      adhesions were well demonstrated both on primary axial and reconstructed
      multiplanar images. The benefits of multiplanar reconstructions are stressed and
      the contribution of soft-tissue injuries to symptomatic diplopia is examined.

PMID- 7719677
TI  - Assessment of the biliary tract by antegrade cholecystography after percutaneous
      cholecystostomy in patients with acute cholecystitis.
AB  - The diagnostic value of formal antegrade cholecystography in a consecutive series
      of 44 patients with scintigraphically confirmed acute cholecystitis, treated by
      percutaneous transperitoneal cholecystostomy, has been evaluated. A total of six
      patients did not have antegrade cholecystography (catheter migration in five
      patients and gangrenous gallbladder perforation in one). Antegrade
      cholecystography was performed in the remaining 38: 10 patients with persisting
      cystic duct obstruction and 28 patients with patent cystic ducts. In the
      persisting cystic duct obstruction group, antegrade cholecystography confirmed
      the cause of gallbladder outflow obstruction as impacted calculi in either the
      gallbladder neck or cystic duct in all patients. In the patent cystic duct group,
      antegrade cholecystography demonstrated the common ducts well in all but two
      patients, and common duct calculi in eight of nine patients. Three patients had
      common duct calculi in non-dilated ducts. Antegrade cholecystography is an easy
      and safe method of clarifying gallbladder pathology in all patients, and can be
      used to evaluate the common duct for associated common duct calculi in most
      patients.

PMID- 7719678
TI  - Sedation and patient monitoring in vascular and interventional radiology.
AB  - A postal survey of British and Irish interventional radiologists was carried out
      in 1991 in order to assess current practice with respect to sedation and
      monitoring of patients during angiography and interventional procedures. The
      response rate was 65%. 49% of patients are fasted prior to angiography and 68%
      prior to interventional procedures. Radiologists participate in obtaining consent
      in 60% of cases. Patients are often (50%) sedated for angiography and usually (62
      94% depending on the procedure) sedated for interventional procedures. Nurses are
      present for most procedures, but are given the task of monitoring the patient's
      vital signs in only 49% of cases. Anaesthetists are present for less than 10% of
      interventional procedures. Pulse oximetry is used routinely in 20% of
      departments, and automatic blood pressure monitors in 16%. 28% of radiologists
      never administer oxygen to patients under sedation, whereas 4% always do. 43% of
      departments have a staffed recovery area. Most vascular/interventional suites are
      stocked with emergency drugs and 80% with a defibrillator. 28% of departments
      report at least one death during or shortly after a procedure during the last 10
      years. 18% of interventional radiologists have taken a refresher course in
      cardiopulmonary resuscitation in the past year. These findings indicate a wide
      variation in practice and a need to standardize practice at a uniform high level.

PMID- 7719679
TI  - Perfusion lung scintigraphy in primary pulmonary hypertension.
AB  - 15 cases of primary pulmonary hypertension were classified into two groups by
      patterns of perfusion lung scintigraphy. Perfusion scintigrams showed multiple,
      small, ill-defined defects (mottled + ve) pattern in eight cases, and the
      remaining seven cases had a normal (mottled - ve) pattern. The mean pulmonary
      arterial pressure in patients with a mottled pattern (54 +/- 10 mmHg) was higher
      than in those with a normal pattern (42 +/- 9 mmHg, p < 0.05). There were no
      significant differences between the two groups in right ventricular ejection
      fraction, partial pressures of oxygen in the arterial blood or alveolo-arterial
      oxygen difference. All the patients with a mottled pattern died within 2 years
      following the lung scintigraphy. There was a significant difference in the
      survival curves between the two groups. Although our statistical analysis must be
      evaluated with caution because of small numbers of patients it is suggested that
      perfusion lung scintigraphy is useful in assessing the prognosis in primary
      pulmonary hypertension.

PMID- 7719680
TI  - Evaluation of "Gastromiro" for bowel opacification during computed tomography:
      comparison with diatrizoate and barium sulphate.
AB  - A new oral formulation of iopamidol, "Gastromiro", was evaluated as a bowel
      contrast agent during abdominal computed tomography (CT). Comparison was made
      with the well established agents sodium/meglumine diatrizoate ("Urografin 370")
      and dilute barium sulphate ("E-Z CAT") in a randomized, blind study of 150
      consecutive patients undergoing abdominal and/or pelvic CT. Parameters assessed
      included quality of bowel opacification, artefact generation, contrast-medium
      palatibility, side effects and cost. No significant difference was found between
      the three contrast media in stomach- or small-bowel opacification. E-Z CAT was
      superior at opacifying the caecum/ascending colon. No compelling reason to choose
      a particular agent was found in the other assessed parameters, but cost is a
      significant factor.

PMID- 7719681
TI  - The influence of film processing temperature and time on mammographic image
      quality.
AB  - High image quality and low radiation levels are essential in mammography. This
      study investigates the effect of changes in processor temperatures and developing
      times on sensitometric findings. These findings were matched with the changes in
      the image quality during similar changes in the developing parameters.
      Temperatures ranging between 35 degrees C and 40 degrees C and developing times
      from 20 s and 50 s were investigated. Higher developing temperatures and
      increased developing times resulted in an increase in film speed and film
      contrast. A definite pattern of change could be demonstrated in film speed and
      film contrast during sensitometry. The same pattern of change could, however, not
      be demonstrated in the quality of phantom images under similar circumstances. The
      base plus fog level was not adversely affected. Sensitometric findings of film
      speed can be effectively used as an indicator of radiation exposure to the
      patient, but cannot be used to establish the developing parameters that will give
      the best image quality. Both these methods should be used to determine which
      processing variables should be used to obtain a combination of the best image
      with radiation as low as possible. Recommendations for optimum processing
      parameters are made for the films and processing chemistry investigated.

PMID- 7719682
TI  - Variations in individual radiation dose in a breast screening programme and
      consequences for the balance between associated risk and benefit.
AB  - In a breast screening programme there is a small but inevitable risk of inducing
      some breast cancers that may appear many years later. This risk has to be
      compared with the benefits of detecting existing cancers at an early stage. In
      the current UK screening programme, for women aged 50-64 years and with a 3-year
      screening interval, the numbers detected greatly exceed the numbers predicted to
      be induced. For the individual, only those with very large and thick breasts who
      also have many views taken during the screening process appear to be at any
      appreciable risk, and the number for whom the risk of induction exceeds the
      probability of cancer detection is of the order of less than 1 per million, a
      risk level normally considered negligible. Results are also presented for younger
      age groups, and for a range of dose levels. Down to age 35 years, induction
      exceeds detection in less than about 1% of those screened, if a 3-yearly interval
      is maintained. The effect of shorter screening intervals is briefly considered.
      All results are based on repeat screening rounds (incidence rounds) using a
      single view and not on the initial (prevalence) round, and use UK data for breast
      cancer incidence. The calculation requires a number of assumptions and is
      intended as a preliminary one, pending more data on doses and numbers of women
      requiring specific numbers of films in screening programmes, but sufficient to
      promote discussion of the appropriate age range for breast screening.

PMID- 7719683
TI  - Simultaneous supra- and infradiaphragmatic irradiation in Hodgkin's disease.
AB  - From 1982 to 1989, 68 patients with Stages IA to IIIB Hodgkin's disease were
      treated by simultaneous supra- and infradiaphragmatic irradiation (SSI-RT). 46
      patients received exclusive radiotherapy for Stages IA and IIA (extended mantle
      field irradiation (EMF) 31, and total lymphatic irradiation (TLI) 15). Combined
      modality treatment including pre-irradiation chemotherapy, was given to 22
      patients (CH-EMF 12 and CH-TLI 10). The median follow-up was 64 months. 5-year
      overall survival was 94% in combined Stages IA and IIA, and 100% in Stage IIIA. 5
      year freedom from relapse was 87% in combined Stages IA and IIA, and 80% in Stage
      IIIA. Toxicity was evaluated in 64 patients. Acute and long term toxicity was
      similar to previously reported data on sequential supra- and infradiaphragmatic
      irradiation. In SSI-RT prior chemotherapy affected pre-irradiation blood counts
      and was associated with delayed post-irradiation haematological recovery. The
      relative mean white blood cell (WBC) decrease ranged from 47% (EMF) to 61% (TLI).
      The mean platelet decrease ranged from 43% (EMF) to 80% (CH-TLI). Both prior
      chemotherapy and total lymphoid irradiation increased haematotoxicity. The mean
      duration of breaks ranged from 3.9 days in EMF to 14.9 days in CH-TLI. The mean
      treatment time, ranging from 43 days in EMF to 54 days in TLI, was significantly
      shorter than in sequential schedules (up to 112 days). Our results indicate that
      SSI-RT is an effective and safe treatment. Its use seems to be limited mainly by
      prior chemotherapy. As compared to sequential schedules, the risk of match line
      overlap is avoided, overall treatment time is decreased, and treatment costs are
      minimized.

PMID- 7719684
TI  - Technical note: computed tomographic dacryocystography.
AB  - The technique of computed tomographic dacryocystography is described. It was
      developed in response to the pre-operative imaging requirements for transnasal
      endoscopic dacryocystorhinostomy, a new minimally invasive operation performed as
      a primary procedure to relieve epiphora. However, it is also helpful in the
      assessment of patients after failed conventional external dacryocystorhinostomy
      when the information provided will help to determine the subsequent surgical
      approach. In addition the technique will assist surgical planning in cases of
      epiphora associated with sinus surgery, facial trauma and maxillofacial tumours
      by determining the site and extent of pathology.

PMID- 7719685
TI  - Technical note: an X-ray fluorescence system for the determination of gold in
      vivo following chrysotherapy.
AB  - This paper describes a low cost mobile measurement system for the determination
      of gold in vivo base around a 153Gd radiation source and a hyper pure germanium
      detector. Early clinical results are also presented to demonstrate the efficacy
      of the system.

PMID- 7719686
TI  - Case report: fat necrosis of the breast appearing as oil cysts with fat-fluid
      levels.

PMID- 7719687
TI  - Case report: bilateral carpal and tarsal synostoses.
AB  - Carpal and tarsal synostoses are uncommon. We report a rare combination of
      bilateral carpal and tarsal synostoses, including fusion across the carpal and
      tarsal rows, and review the literature.

PMID- 7719688
TI  - Case report: colonic obstruction following small bowel barium study.
AB  - A case is described in which inspissated barium was retained in the colon for 16
      months before causing large bowel obstruction. To our knowledge this is the first
      case described in which the time interval between barium ingestion and the onset
      of symptoms was more than a few weeks. Scybalum formation is due to resorption of
      water from the barium sulphate, which although less common with modern
      preparations, still appears to be possible in certain high-risk patients.
      Prolonged retention of barium should be avoided by increased awareness of the
      problem, encouraging patients to eat and drink normally after the examination,
      encouraging mobility and administration of lactulose in high risk patients.

PMID- 7719689
TI  - Case report: radiation-induced vasculopathy implicated by depressed blood flow
      and metabolism in a pineal glioma.
AB  - A case of radiation-induced vasculopathy of a pineal glioma was presented with
      haemodynamic and metabolic changes before and after radiotherapy. After radiation
      of 60 Gy with conventional fractionation (1.8-2.0 Gy daily, 5 days per week),
      regional blood flow, oxygen extraction fraction, metabolic rate of oxygen,
      kinetic metabolic rate of glucose and the rate constants (K2, K3) were markedly
      depressed (20% or greater) compared with the pre-irradiated study. 7 months after
      radiotherapy, the patient developed transient transient episodes of both right
      and left upper limb convulsion, terminating in generalized convulsion. When she
      developed status epilepticus, computed tomography showed extensive low density
      areas in the territory supplied by the right middle cerebral and the right
      posterior cerebral arteries. Cerebral angiography revealed diffuse stenosis at
      both carotid bifurcations and at the origins of the right posterior communicating
      and posterior cerebral arteries. Haemodynamic and metabolic depression therefore
      implicated radiation-induced vasculopathy in the present case.

PMID- 7719690
TI  - Case report: imaging of a bilobed gallbladder.
AB  - Imaging of the gallbladder demonstrates a wide range of anatomical variants,
      including anomalies in location, number and shape. Duplication anomalies are
      quite rare and are characterized by a large variety of configurations depending
      on the size and degree of fusion of the two lobes, and on the number and
      disposition of the cystic ducts. We present a case of a deeply cleft, bilobed
      gallbladder imaged by computed tomography (CT), ultrasonography (US) and oral
      cholecystography (OCG). The anomaly consisted of complete duplication of the body
      and fundus into two distinct and separated lobes both of which entered a single
      infundibulum. Awareness of congenital gallbladder variants may help in
      recognizing and correctly classifying gallbladder abnormalities, thus preventing
      misdiagnoses.

PMID- 7719691
TI  - Case report: unexplained symptomatic metaphyseal sclerosis in children: three
      cases.

PMID- 7719692
TI  - Case of the month: pseudo-tumour of the postero-superior mediastinum.

PMID- 7719693
TI  - Short communication: quantitative macroradiography with biochemical correlation
      of children with renal osteodystrophy.

PMID- 7719694
TI  - Percutaneous pigtail catheter straighteners--a warning.

PMID- 7719695
TI  - Possible hazard associated with the use of the "FemoStop" groin compression
      device.

PMID- 7719696
TI  - [Fosinopril--2 years in practice. Experience with 30,000 patients].

PMID- 7719697
TI  - A linkage study with D5 dopamine and alpha 2C-adrenergic receptor genes in six
      multiplex bipolar pedigrees.
AB  - Six kindreds containing multiple cases of manic-depressive illness were genotyped
      with highly polymorphic microsatellite polymorphisms for the D5 dopamine and
      alpha 2C-adrenergic receptor genes. Evidence of linkage was not found assuming
      either autosomal dominant or recessive transmission. The non-parametric sib pair
      test did not yield evidence of linkage.

PMID- 7719698
TI  - The familial aggregation of panic disorder by source of proband ascertainment.
AB  - Estimates of familial aggregation of psychiatric disorder obtained from relatives
      of probands ascertained in treatment settings may differ from estimates obtained
      from relatives of probands ascertained from the general population. In this paper
      we investigate this hypothesis for panic disorder, by comparing the degree of
      familial aggregation of panic disorder in relatives of probands with panic
      disorder ascertained from either a specialty anxiety clinic, a specialty
      depression clinic or a population survey, respectively. Results for panic
      disorder do not suggest that familial rates are associated with source of proband
      ascertainment. Results show that the rates of panic disorder in relatives were
      similar by proband source. This suggests that familial rates of panic disorder
      are not associated with proband ascertainment and that selecting probands from
      treatment clinics rather than from the general population does not necessarily
      lead to greater estimates of familial aggregation of panic disorder. Further
      research is needed to determine if this finding can be generalized to other
      psychiatric disorders.

PMID- 7719699
TI  - Estimating the morbidity risk for diseases having a variable age at onset.
AB  - The morbidity risk assesses the risk of manifesting illnesses having a variable
      age at onset. We reviewed the conceptual derivation and critical assumptions of
      various methods for estimating morbidity risk by classifying them into two
      approaches. One approach uses an age at onset distribution as a weighting system.
      A second approach uses methods from survival analysis. Because survival methods
      estimate the morbidity risk and age at onset distribution simultaneously, they
      are preferable to weighting methods. Among weighting methods, Stromgren's
      estimator or Risch's maximum likelihood estimate are the methods of choice; the
      Kaplan-Meier estimator is the preferred survival analysis approach.

PMID- 7719700
TI  - Linkage analysis in two schizophrenic families originating from a restricted
      subpopulation of Finland.
AB  - We report here linkage data on two families with multiple cases of schizophrenia
      originating from the genetically isolated population of Finland. We analyzed
      chromosomal DNA regions containing relevant candidate genes for schizophrenia and
      chromosomal regions which have been among the most widely studied in
      schizophrenia research due to associations between chromosomal anomalies and
      schizophrenia observed in certain families or populations. These include the
      chromosomal regions 5q11-q13, 11q and 15q21 as well as gene loci coding for
      components of dopamine, serotonin and amino acid transmitter pathways. No
      evidence for linkage to any of the chromosomal regions or candidate genes could
      be obtained, our data in fact suggested exclusion of all these regions as the
      site for major predisposing loci for schizophrenia in our families. On the 11p
      region the lod scores obtained deviated in the two families, but the difference
      remained statistically insignificant. The data emphasize the importance of
      analyzing families even with restricted genetic background separately since locus
      heterogeneity is likely to be detected not only between ethnic groups but also
      between diagnostic classes of the schizophrenia spectrum of diseases.

PMID- 7719701
TI  - Direct sequencing of the reserpine-sensitive vesicular monamine transporter
      complementary DNA in unipolar depression and manic depressive illness.
AB  - The reserpine model and the reduced monoamine hypothesis of the depressive
      symptom spectrum suggest that the reserpine-sensitive brain vesicular monoamine
      transporter (VMT) is a candidate for susceptibility to affective disorder. VMT
      nonselectively accumulates cytoplasmic biogenic monoamine neurotransmitters into
      the storage vesicles of presynaptic neurons and blood platelets. Complementary
      DNA (cDNA) synthesized from platelet VMT mRNA was analyzed in 17 patients meeting
      DSM-III-R diagnostic criteria for major depressive or bipolar disorder and in
      four healthy controls, using polymerase chain reaction (PCR) amplification and
      direct sequencing. PCR sequencing of the protein coding region failed to reveal
      changes in the deduced amino acid sequence of the platelet/brain VMT
      (approximately 36,000 base pairs sequence screened). The results indicate that
      alterations in the primary structure of the VMT are not generally involved in the
      pathogenesis of unipolar depression and manic depressive illness.

PMID- 7719702
TI  - Schizophrenia and glutamate receptor genes.
AB  - Nine multiplex schizophrenia families were genotyped with polymorphisms for the
      GLUR5 and NMDAR1 glutamate receptor subunit genes. Using the lod score technique,
      evidence of linkage was not found assuming either dominant or recessive
      transmission. Similarly, the non-parametric sib pair test did not yield
      significant evidence of linkage.

PMID- 7719703
TI  - Association and haplotype analysis at the tyrosine hydroxylase locus in a
      combined German-British sample of manic depressive patients and controls.
AB  - Tyrosine hydroxylase (TH) is the key enzyme in the synthesis of catecholamines
      and may therefore be of aetiological relevance in the development of psychiatric
      illness. Hipolar affective disorder association studies, with restriction
      fragment length polymorphisms located in flanking regions of the TH gene, have
      shown conflicting results. Alleles of a tetranucleotide repeat polymorphism (TH4)
      located in intron 1 of the gene were tested for association with bipolar
      affective disorder in a combined German and British sample of 183 bipolar
      patients and 209 healthy control probands. No differences in TH4 allele
      frequencies were found in the two groups. A subset of patients and controls was
      typed with the flanking markers Ty7/BglII and pJ4.7/TaqI and frequencies of two
      locus haplotypes were estimated. Linkage disequilibrium was found between TH4-Ty7
      and TH4-pJ4.7. Haplotype frequencies did not differ between patients and
      controls.

PMID- 7719704
TI  - Linkage analysis between manic depressive illness and the dopamine beta
      hydroxylase gene.
AB  - The dopamine beta-hydroxylase (DBH) gene is a candidate gene in manic depressive
      illness. DBH is required for conversion of dopamine to norepinephrine, the third
      step in catecholamine biosynthesis. A few earlier linkage studies have found low
      to moderately positive lod scores in manic depressive families for ABO which is
      closely linked to DBH. Based on several studies an association between manic
      depressive illness and ABO blood type has been suggested. Mutations at the DBH
      locus might thus be involved in the etiology of manic depressive illness in some
      families. The DBH gene is reported here as unlikely to be a major gene causing
      manic depressive illness in a large family. Linkage was excluded assuming a
      dominant mode of transmission. Several methods were used to minimize
      misclassification.

PMID- 7719705
TI  - Analysis of GABAA receptor subunit genes in multiplex pedigrees with manic
      depression.
AB  - The gamma-aminobutyric acid (GABA) neurotransmitter system has been implicated in
      the pathogenesis of manic depression. Tests of this hypothesis can now be carried
      out due to the recent characterization of simple sequence repeat polymorphisms
      for the GABAA receptor alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, beta 1, beta
      3 and gamma 2 subunit genes. Using both parametric and non-parametric methods, we
      tested for linkage between manic depression and these polymorphisms in six multi
      generational pedigrees. No evidence of linkage was found.

PMID- 7719706
TI  - Molecular characterization and chromosome localization of a human angiotensin II
      AT2 receptor gene highly expressed in fetal tissues.
AB  - The gene encoding the human angiotensin II (AT2) receptor exists as a single copy
      and contains no intron in its coding region. Its nucleotide sequence is identical
      to that of cDNA clones isolated from human myometrial library. In addition,
      binding properties of the corresponding receptor expressed in COS cells are
      identical to those of endogenous AT2 receptors from human myometrium. The human
      AT2 receptor gene translates into a polypeptide of 363 amino-acid residues that
      belongs to the seven transmembrane domains receptor superfamily. This polypeptide
      shows 92% amino-acid sequence homology and the same pharmacological profile as
      AT2 receptors recently isolated from rat and mouse. The AT2 receptor gene maps to
      the X chromosome in man (region Xq24-q25) as well as in mouse (region XA2-A4).
      These findings open new perspectives regarding a potential involvement of AT2
      receptors in X-linked congenital diseases. Expression of AT2 receptor mRNA is
      found in human myometrium, fallopian tubes and adrenals, and at extremely high
      levels in fetal kidney and intestine. These results indicate that AT2 receptor
      gene expression is regulated during human embryonic development, and support the
      hypothesis that AT2 receptors may play a role in organogenesis.

PMID- 7719707
TI  - Expression of rat NK-2 (neurokinin A) receptor in E. coli.
AB  - With the goal of obtaining sufficient functional protein for structural analysis,
      rat neurokinin-2 receptor was produced in Escherichia coli by linking it to the
      periplasmic maltose-binding protein. As a first step, we present a biochemical
      and pharmacological investigation of the recombinant receptor. Western-blots
      showed that the fusion protein was associated with the membranes. The agonist
      [4,5-3H-Leu9]neurokinin A and the NK-2 antagonist [3H]SR48,968 bound to the
      receptor in a highly specific manner. Saturation binding of the [3H]agonist
      demonstrated a single class of receptors (KD = 10.5 nM, Bmax = 2.5 pmol/mg
      protein). The [3H]antagonist bound with higher affinity to a larger receptor
      population (KD = 0.2 nM, Bmax = 7.2 pmol/mg protein). Competition of [3H]agonist
      binding with other agonists demonstrated a potency order of: neurokinin A >
      [Nle10]NKA(4-10) = [beta-Ala8]NKA(4-10) >> substance P >>> senktide Against the
      [3H]antagonist, agonists were only partially inhibitory. Selective NK-2
      antagonists inhibited binding of both [3H]ligands with an identical order of
      potency: SR48,968 >> R396 > MEN10,376, which is consistent with NK-2 receptor
      pharmacology in rat tissue.

PMID- 7719708
TI  - Distinctive functional properties of the neuronal BII (class E) calcium channel.
AB  - Functional diversity of voltage-dependent calcium channels (VDCC) is primarily
      due to the existence of six distinct genes of the channel-forming subunit alpha
      1, which can be further classified into the L-type and neuronal non-L-type
      subfamilies. We have examined functional properties of the calcium channel BII
      expressed from the cloned cDNA, in Xenopus oocytes, and compared the results with
      the other members of the non-L-type subfamily, the BI and BIII channels. The BII
      channel is a high voltage-activated calcium channel pharmacologically features by
      its unique sensitivity to the inorganic blocker Ni2. The decaying component of
      the BII current shows high sensitivity to Ni2+ similar to that of the low voltage
      activated channels and the R-type channel in cerebellar granule cells, whereas
      the sustained component is relatively resistant to Ni2+ as are the other high
      voltage-activated calcium channels. Dihydropyridines, omega-CgTx-GVIA, and omega
      Aga-IVA, which have been used to discriminate L-, N-, and P-types, do not affect
      the BII current. The mode of modulation of the BII channel by auxiliary subunits
      is strikingly different from that observed in the L-type channels. Both
      activation and inactivation rates of the BII current are decelerated by
      coexpression of the beta subunit, and this effect is cancelled by further
      coexpression of the alpha 2 subunit. In situ tissue distribution studies indicate
      a higher level of BII mRNA expression in the hippocamus compared to other brain
      regions, revealing important difference in the relative abundance of BI, BII, and
      BIII channels in brain tissues. Overall, the results suggest that the BII channel
      forms a novel functional category of VDCC that is different from T-, L-, N-, and
      P-type.

PMID- 7719709
TI  - Molecular characterization of the human EAA5 (GluR7) receptor: a high-affinity
      kainate receptor with novel potential RNA editing sites.
AB  - Several cDNA clones encoding EAA5 receptor polypeptides were isolated from a
      human fetal brain library. The EAA5 cDNAs demonstrated an 88.7-90.1% nucleotide
      identity with rat GluR7 cDNAs. The nucleotide sequence of EAA5 would encode a 919
      amino acid protein, that has a 97.7-98.9% identity with the rat GluR7 receptor.
      Two variation of the EAA5 cDNA were identified which result in amino acid
      substitutions in the predicted extracellular amino-terminal region; Ser310-->Ala
      and Arg352-->Gln. These variations can be attributed to RNA editing involving T-
      >G and G-->A substitutions. Both the location (with respect to glutamate
      receptors), and the nucleotides involved, in this putative RNA editing are novel
      and may therefore involve novel mechanisms. Ligand binding studies with membranes
      of transfected COS-1 cells expressing EAA5 polypeptides demonstrate a rank order
      of ligand affinity similar to that observed with the rat GluR7 receptor, and a
      dissociation constant for kainate (2.72 +/- 0.12 nM (n = 3)) that is
      approximately 20- to 30-fold higher than that observed for the rat GluR7
      receptor. All of the ligands tested had a higher affinity for the human EAA5
      receptor as compared to the rat GluR7 receptor. This report provides another
      example of pharmacological differences for similar receptors across species.

PMID- 7719710
TI  - Development of spontaneous seizures over extended electrical kindling. II.
      Persistence of dentate inhibitory suppression.
AB  - The effect of an extended program of perforant path or amygdala kindling on
      paired-pulse suppression in the dentate gyrus was studied in male hooded rats.
      Repeated kindling stimulations were delivered twice or three times daily until
      either 300 stimuli had been delivered or generalized convulsions had been
      observed to occur spontaneously. Paired-pulse suppression was monitored prior to
      and over the course of kindling using a standard variable interval paradigm. We
      also used a variable intensity paradigm in which the intensity of the
      conditioning pulse was varied while the test pulse intensity was fixed at 600
      microA and the interpulse interval was fixed at 30 ms. Both procedures revealed
      progressive increases in paired-pulse suppression which persisted over the course
      of kindling. This increased inhibition also persisted in animals which developed
      spontaneous seizures. The variable intensity paired-pulse procedure also allowed
      us to monitor facilitation effects which were relatively uncontaminated by
      recurrent inhibition (when the conditioning pulse intensity was low). Kindling
      was found to increase paired-pulse facilitation. With the standard variable
      interval paradigm, these increases in facilitation masked the increases in
      suppression.

PMID- 7719711
TI  - Septohippocampal neurons in the rat septal complex have substantial glial
      coverage and receive direct contacts from noradrenaline terminals.
AB  - The ultrastructure of septohippocampal neurons in the septal complex and their
      relations with catecholamine, principally noradrenaline, terminals were examined
      in single thin sections. Projection neurons were identified by retrograde
      transport of wheat-germ agglutinated apo-horseradish peroxidase conjugated to
      colloidal gold particles (WAHG) following an injection into the hippocampal
      formation of anesthetized adult rats. After a 1 day survival, sections through
      the septal complex were labeled with antibodies to tyrosine hydroxylase (TH) or
      dopamine-beta-hydroxylase (DBH). By light microscopy, numerous processes with TH-
      and DBH-immunoreactivity were near neurons containing retrogradely transported
      WAHG. By electron microscopy, most WAHG was associated with lysosomes,
      multivesicular and 'sequestration' bodies in the cytoplasm of perikarya and large
      dendrites. WAHG-labeled perikarya (n = 114) had a large amount of astrocytic
      coverage (> 60% of surface) and a low amount of terminal coverage (< 25%). WAHG
      labeled perikarya and dendrites were either directly contacted by TH- or DBH
      labeled terminals or abutted glial processes apposed to TH- or DBH-labeled
      terminals. Immunoreactivity for TH and DBH was found primarily in axons and axon
      terminals. The morphology and synaptic associations of TH-labeled terminals was
      similar to that reported previously. DBH-labeled terminals (n = 314; 0.5 +/- 0.2
      microns in diameter) contained numerous small clear vesicles and from 0-4 large,
      dense-core vesicles. DBH-containing terminals: (1) contacted perikarya and
      dendrites (58%), 10% of which contained WAHG; (2) were closely apposed to other
      terminals (7%); or (3) were separated by glial processes (35%). DBH-labeled
      terminals formed chiefly symmetric synapses on perikarya. However, most DBH
      containing terminals formed both asymmetric and symmetric synapses on the shafts
      of small dendrites, suggesting both excitatory and inhibitory functions for
      noradrenaline terminals on septal neurons. The results demonstrate that
      septohippocampal neurons (1) are mostly engulfed by astrocytes and have very
      little terminal coverage; (2) are both directly contacted (synapses) and
      indirectly contacted (appositions to apposing astrocytes or axon terminals) by
      catecholamine, particularly noradrenaline, terminals.

PMID- 7719712
TI  - Aggregation of amyloid precursor proteins by aluminum in vitro.
AB  - The effect of various metal ions on aggregation of human recombinant amyloid
      precursor protein (APP) in vitro was investigated based on characterizations of
      altered migration on SDS-PAGE or immunoblots. Most biological metal ions tested
      had no significant effect on aggregation of APP. In contrast, AlCl3 in particular
      promoted aggregation of APP or APP-CT105 in a dose dependent manner. This effect
      of AlCl3 on APP mobility shift was prevented or reversed by the metal chelator,
      EDTA. Amorphous aggregates were observed in AlCl3 treated APP when examined by
      EM. These results suggest that aluminum may play a role in the pathogenesis of AD
      by directly promoting aggregation of APP.

PMID- 7719713
TI  - Purification, pharmacological characterization and photoaffinity labeling of
      sigma receptors from rat and bovine brain.
AB  - The sigma receptor/binding site, found in the brain and periphery, binds
      haloperidol, (+)-benzomorphans, N-propyl-3-(3-hydroxyphenyl)-piperidine (3-PPP)
      and certain atypical neuroleptics with high affinity. We have succeeded in ca.
      6,000-fold purification of protein(s) from rat and bovine cerebellum which
      display pharmacology characteristic of the sigma receptor. This purification was
      achieved by affinity chromatography using a Sepharose gel linked to a new high
      affinity ligand, (S)-3-(3-methoxyphenyl)-3'-oxo-3'-phenyl-N-propylpiperidine, an
      analog of (S)-3-PPP. Elution of the affinity column with haloperidol afforded
      material which, after reconstitution into bimolecular lipid vesicles, was
      pharmacologically characterized by specific radioligand binding assays using
      [3H]haloperidol combined with competitive displacement using appropriate
      selective ligands. Comparison of the relative rank orders of potency of the
      ligands in these selective sigma receptor assays corresponded well with values
      obtained with tissue homogenates. The observed enantioselectivity for the binding
      of SKF-10,047 and cyclazocine suggests that the material purified corresponds to
      the sigma 1 receptor subtype. SDS-PAGE indicated that the purified material
      consisted of two bands of approximate molecular masses 65 and 63 kilodaltons.
      Photoaffinity labeling of the affinity-purified receptor with [3H]azido-DTG led
      to incorporation of the label into material of molecular mass 50-70 kDa, by
      slicing of SDS gels, while similar photolabeling of crude cerebellar homogenates
      led to exclusive labeling of a 29 kDa polypeptide, as found previously using
      other tissues. Molecular sizing under non-denaturing conditions indicated the
      photolabeled species is a labile large receptor complex of mass ca. 300-500 kDa
      which gradually breaks down upon standing at -80 degrees C into the lower mass
      (50-70 kDa) material. The sigma receptor ligand binding subunit, which appears to
      be of the sigma 1 subtype, appears to be contained within the 29 kDa polypeptide,
      which may be a subunit of the 63-65 kDa protein, which in turn appears to be a
      component of a much larger receptor complex. It further appears that the 29 kDa
      polypeptide is readily dissociable from a larger photolabeled sigma receptor
      complex in tissue homogenates, but does not dissociate from the photolabeled
      affinity-purified CHAPS-solubilized sigma receptor.

PMID- 7719714
TI  - Activity-dependent depression of monosynaptic fast IPSCs in hippocampus:
      contributions from reductions in chloride driving force and conductance.
AB  - Whole-cell recordings techniques were used to record pharmacologically isolated
      fast inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal neurons from rat
      hippocampal slices. Repetitive extracellular stimulation up to 10 Hz
      progressively reduced steady-state fast IPSC amplitude. At low stimulation
      frequencies (up to 1 Hz), this attenuation was characterized by a positive shift
      of IPSC reversal potential with no change in IPSC conductance. Above 1 Hz
      stimulation, fast IPSC depression was associated with changes in both reversal
      potential and IPSC conductance. Use-dependent depression at low frequencies was
      prevented when cells were chloride-loaded using cesium chloride based
      intracellular solutions. These findings suggest that activity-dependent
      depression of fast IPSCs at low stimulus frequencies results entirely from a
      reduction in chloride driving force, stemming from intracellular chloride
      accumulation. Activity-dependent changes in fast IPSC conductance occur only at
      stimulation rates above 1 Hz.

PMID- 7719715
TI  - Thalamic reticular input to the rat visual thalamus: a single fiber study using
      biocytin as an anterograde tracer.
AB  - This study describes the axonal projections of single thalamic reticular (TR)
      neurons within the visual thalamus in rats. Experiments were performed under
      urethane anesthesia and reticular cells were labeled by extracellular or
      juxtacellular microiontophoretic applications of biocytin. The axonal
      arborizations of 19 TR cells projecting to the dorsal lateral geniculate nucleus
      (DLG) or to the lateral dorsal/lateral posterior complex (LD/LP) were
      reconstructed from serial horizontal sections. It was found that single TR cells
      projected within the limits of a single thalamic nucleus, either the DLG or the
      LD/LP complex, where their terminal fields formed rostrocaudally oriented rods
      (length: approximately 800 microns; diameter: approximately 100 microns) densely
      packed with grape-like boutons and varicosities. In addition, none of the labeled
      TR cells possessed recurrent axonal collaterals that ramified within the
      reticular complex itself. The functional implications of these morphological data
      for the synchronization of thalamic oscillations are discussed.

PMID- 7719716
TI  - Temperature dependence of EEG frequencies during natural hypothermia.
AB  - We have investigated the effects of changes in brain temperature on the
      electroencephalogram (EEG) during entrance into daily torpor, a natural
      hypothermic state, in the Djungarian hamster. A systematic shift of single EEG
      frequencies was found as cortical temperature decreased. The relation between EEG
      frequency and cortical temperature was very similar to the temperature dependence
      of the Na(+)-K(+)-pump, suggesting that the pump is the rate-limiting step in
      determining EEG frequency.

PMID- 7719717
TI  - Proliferative zones of postnatal rat brain express epidermal growth factor
      receptor mRNA.
AB  - Two ligands for the epidermal growth factor receptor (EGF-R), EGF and
      transforming growth factor-alpha (TGF alpha), have recently been shown to
      influence the proliferation, differentiation or survival of diverse populations
      of fetal and neonatal neuronal and glial cells in culture. These findings suggest
      that EGF, TGF alpha, or another EGF-R ligand play a role in the regulation of
      similar cellular developmental events in vivo. In the present study, in situ
      hybridization with an 35S-labeled cRNA probe was used to determine if mRNA for
      EGF-R is expressed in two principal germinal zones of the postnatal rat brain,
      the forebrain ventricular/subventricular zone and the cerebellar external granule
      layer. Cells labeled with the EGF-R cRNA were distributed throughout the
      subventricular zone, particularly in the dorsolateral aspect, from birth to
      adulthood, although the numbers of labeled cells as well as the density of
      hybridization diminished during development. In the developing cerebellum,
      virtually all cells in the external granule layer were densely labeled with the
      EGF-R cRNA, as were numerous perikarya throughout the molecular layer. EGF-R mRNA
      was also transiently expressed at lower levels by neurons of the internal granule
      layer and deep cerebellar nuclei. By adulthood, cerebellar expression of EGF-R
      mRNA was not detected. These results demonstrate prominent expression of EGF-R
      mRNA within germinal zones of the developing brain and indicate a role for EGF,
      TGF alpha, or another member of the EGF-related family in regulating the
      activities of neuronal and glial progenitor cells in vivo.

PMID- 7719718
TI  - Further studies on the effects of chronic clozapine on regional extracellular
      dopamine levels in the brain of conscious rats.
AB  - The effect of chronic oral treatment with clozapine (20 mg/kg daily for 21 days)
      on the extracellular concentrations of dopamine, dihydroxyphenylacetic acid and
      homovanillic acid in the dorsolateral anterior striatum, nucleus accumbens and
      frontal cortex was studied by microdialysis in conscious rats. Basal levels of
      dopamine and its metabolites in the three brain regions of rats treated
      chronically with clozapine were not significantly different from those of vehicle
      treated rats. A subcutaneous challenge dose of clozapine (20 mg/kg) significantly
      increased the extracellular concentrations of dopamine and its metabolites in the
      three brain regions, with no differences between chronic vehicle- and clozapine
      treated rats.

PMID- 7719719
TI  - The response pattern of noradrenaline release to repeated stress in the
      hypothalamic paraventricular nucleus differs according to the form of stress in
      rats.
AB  - The effect of two repeated forms of stress, manual restraint and tail-pinch, on
      noradrenaline (NA) release in the hypothalamic paraventricular nucleus of the rat
      was examined by intracerebral microdialysis. Manual restraint significantly
      increased NA release, but the stimulatory effect gradually declined when the
      stress was repeated at intervals of 120 min. High K+ induced a great increase in
      NA release even when manual restraint produced no significant effect on NA
      release. In contrast, tail-pinch significantly increased NA release to a greater
      extent than manual restraint, and the increase in NA release did not change when
      the stress was repeated three times at intervals of 120 min. These results
      suggest that desensitization of NA neurons ending in the hypothalamic
      paraventricular nucleus occurs in response to painless stress, such as manual
      restraint, whereas no attenuation of NA release is caused by repeated stress
      accompanied by pain, such as tail-pinch.

PMID- 7719720
TI  - Potentiating effects of methamphetamine on the hyperactivity of microencephalic
      rats treated prenatally with methylazoxymethanol: possible implication of
      hyperdopaminergia.
AB  - Microencephalic rats induced by methylazoxymethanol (MAM) were observed to have
      notable hyperactivity compared to control rats, as measured by several behavioral
      parameters in an automated field apparatus. Acute injection of the stimulant
      drug, methamphetamine (MAP), produced an increase in the incidence of locomotion
      and rearing in control rats, and this stimulatory effect of MAP on motor activity
      was markedly potentiated in MAM rats. Chronic MAP treatment did not change D1 or
      D2 dopamine receptor densities in either control or MAM rats. From these results,
      it was suggested that augmented dopaminergic functions may contribute to the
      hyperactivity seen in MAM rats.

PMID- 7719721
TI  - Progressive hippocampal loss of immunoreactive GLUT3, the neuron-specific glucose
      transporter, after global forebrain ischemia in the rat.
AB  - Brain damage after global forebrain ischemia is worsened by prior hyperglycemia
      and ameliorated by antecedent hypoglycemia. To assess whether GLUT3, the neuron
      specific glucose transporter and its mRNA, are affected by cerebral ischemia, we
      investigated the hippocampal pattern of GLUT3 immunoreactivity and GLUT3 gene
      expression 1, 4 and 7 days after global forebrain ischemia in a rat 2-vessel
      occlusion model. We used a newly generated, specific, C-terminally directed
      polyclonal antiserum against GLUT3 to stain coronal frozen sections. Thionin
      staining and the microglial marker, OX42, indicated the extent of ischemic damage
      in hippocampus and correlated with GLUT3 loss. One day after ischemia, no
      significant change in hippocampal GLUT3 immunoreactivity was observed; by 4 days
      however, there was consistent and pronounced loss; and at 7 days the loss of
      GLUT3 staining was maximal. The greatest loss of GLUT3 staining was in the CA1
      region, especially the strata oriens and radiatum of Ammon's horn. By contrast,
      GLUT3 staining was undiminished in the stratum lacunosum moleculare, in the mossy
      fibers of the lateral aspect of CA3 and in all but the inner-most portion of the
      molecular layer of the dentate gyrus, immediately adjacent to the granule cells.
      GLUT3 mRNA levels were not significantly altered at 24 hours and significantly
      declined at 4 and 7 days after ischemia in the CA1 pyramidal layer. These data
      are consistent with the pattern of neuronal loss and microglial activation in
      hippocampus. Loss of GLUT3 may affect the availability of glucose, and possibly
      the viability of ischemically damaged neurons.

PMID- 7719722
TI  - Acetylcholine and central respiratory control: perturbations of acetylcholine
      synthesis in the isolated brainstem of the neonatal rat.
AB  - The brainstem neurochemical processes which support spontaneous ventilation are
      not known. Cholinergic transmission may play an important role. If this is true,
      perturbations in acetylcholine (ACh) turnover should alter ventilatory output in
      a predictable manner. Using the isolated superfused brainstem-spinal axis from
      the neonatal rat, the effects of modifiers of ACh synthesis on spontaneous C-4
      (phrenic) output were determined. 3-Bromopyruvate and hydroxycitrate, inhibitors
      of acetyl-CoA (substrate for ACh synthesis) formation, caused depression of the C
      4 output in a dose-dependent manner when added to the superfusate.
      Triethylcholine, a false-transmitter generating choline analog, caused a similar
      depression. Citrate, a cytosolic precursor to acetyl-CoA formation, caused
      stimulation of C-4 (phrenic) output. The stimulatory effects of citrate were
      blocked by the muscarinic cholinergic blocker, atropine. These findings are
      consistent with the view that the ACh synthetic pathway provides a continuous and
      important input to the normal brainstem elements that support ventilation.

PMID- 7719723
TI  - Hyperthermia nullifies the ameliorating effect of dizocilpine maleate (MK-801) in
      focal cerebral ischemia.
AB  - The present study was inspired by two previous findings from the laboratory. The
      first was that dizocilpine maleate (MK-801) fails to reduce infarct size when the
      middle cerebral artery (MCA) is permanently occluded by an intraluminal filament
      technique in rats. In seeking the reasons for this we measured temperature and
      found that the body temperature of occluded animals increases to 39.0-39.5
      degrees C during the first 2-3 h. In order to explore whether the rise in
      temperature was responsible for the lack of effect of MK-801, two groups of
      animals were studied, both containing animals which were subjected to 2 h of
      transient MCA occlusion and given MK-801 15 min before, as well as 6 and 24 h
      after ischemia. In one group, temperature was allowed to rise spontaneously
      during ischemia (39.0-39.5 degrees C). In the other, body temperature was
      maintained close to normal during ischemia, and for the first 6 h
      postischemically, by cooling of the ambient air. Infarct volume was assessed by
      triphenyltetrazolium chloride staining after 48 h of recovery. The results showed
      that MK-801 failed to reduce infarct size in animals whose body temperature rose
      during ischemia. In contrast, the drug markedly reduced infarct volume in
      temperature-controlled animals; in fact, 5/8 animals had no infarcts but
      selective neuronal damage only. The results suggest that amelioration of focal
      ischemic damage cannot be expected if body and brain temperature is allowed to
      rise above normal.

PMID- 7719724
TI  - Alteration of cortical and hippocampal cholinergic activities following lesion of
      the mammillary bodies in mice.
AB  - The effects of ibotenic acid lesions of the mammillary bodies (MM) on the sodium
      dependent high affinity choline uptake (SDHACU) velocity into both the
      hippocampus and the frontal cortex were investigated in this study in either a
      quiet or an active (exploration of a T-maze) condition. Results showed that MM
      lesion globally produced a significant decrease of both hippocampal and cortical
      SDHACU. However, the magnitude of this decrease was not significantly different
      in the active as compared to the quiet condition. These findings suggest that MM
      lesion alters the tonically but not phasically active transynaptic control of
      cortical and hippocampal cholinergic activities.

PMID- 7719725
TI  - c-fos expression in the paraventricular nucleus of the hypothalamus following
      intracerebroventricular infusions of neuropeptide Y.
AB  - Intracerebroventricular (i.c.v.) infusions of neuropeptide Y (NPY) (2500 pmol)
      induced c-fos protein in the paraventricular nucleus (PVN) of intact male rats 60
      min later. The greatest expression was observed in the dorsal (parvicellular)
      region of the PVN; there were intermediate levels in the lateral (magnocellular)
      and lowest ones in the medial (parvicellular) regions. Allowing rats to eat
      during the post-infusion interval did not modify this pattern of c-fos
      expression. Depriving rats of food for either 24 or 48 h did not induce
      recognisable expression of c-fos in the PVN, and allowing 24 h-deprived rats to
      eat also had no effect on PVN c-fos. Plasma insulin was increased by i.c.v. NPY,
      and raised still further in rats that were allowed to eat following NPY
      infusions. However, plasma glucose was not altered by either treatment. Food
      deprived rats had low levels of insulin, but unaltered blood glucose, compared to
      controls. These results show that NPY can induce c-fos expression in both
      parvicellular and magnocellular areas of the PVN. The pattern of expression
      within the PVN seems to differ from that induced by other peptides, such as
      angiotensin II, vasopressin and corticotropin-releasing factor, suggesting that
      distinct populations of neurons are activated by different peptides within the
      complex structure of the PVN. Food deprivation does not induce c-fos expression
      within the PVN, though other studies have shown that NPY levels and release are
      both increased, so there is no simple relation between current energy state,
      blood levels of either glucose or insulin and c-fos expression within the PVN.

PMID- 7719726
TI  - Effects of peripheral versus central administration of the endogenous
      glucocorticoid, corticosterone, and the glucocorticoid receptor agonist, RU
      28362, on LH release in male rats.
AB  - The current studies evaluated the effects of the synthetic glucocorticoid
      receptor (GR) agonist, RU 28362, and the endogenous, non-selective receptor
      ligand, corticosterone (Cort), on pituitary luteinizing hormone (LH) secretion in
      male rats. Steroids were injected subcutaneously (s.c.) in animals previously
      implanted with intracardiac venous catheters, or administered
      intracerebroventricularly (i.c.v.) to other groups of animals. A dose
      proportionate decrease in plasma LH was observed following either s.c. or i.c.v.
      administration of RU 28362; pretreatment with the GR antagonist, RU 38486,
      blunted the inhibitory impact of RU 28362 on circulating LH. In other
      experiments, s.c. injection of Cort elicited divergent, dose-dependent patterns
      of LH release. While the lowest peripheral dose (0.25 mg Cort/kg) promoted a
      transient elevation in plasma LH, higher doses exerted a progressively greater
      inhibitory effect on hormone release. The suppressive effects of the highest s.c.
      dose (2.5 mg Cort/kg) were reversed by pretreatment with the RU 38486, but not by
      the mineralocorticoid receptor antagonist, RU 26752. Plasma LH levels were
      transiently elevated following i.c.v. administration of graded doses of Cort. The
      lowest dose (0.1 microgram Cort/rat) only facilitated LH release, but higher
      doses (1.0 and 10.0 micrograms/animal) elicited a biphasic LH response, which was
      characterized by an initial elevation, then subsequent reduction in plasma LH
      below preinjection baseline levels. Prior administration of the mineralocorticoid
      receptor antagonist, RU 26752, attenuated the stimulatory impact of i.c.v. Cort
      on LH release, while both RU 26752 and RU 38486 reversed the secondary decline in
      plasma LH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719727
TI  - Differential involvement of the right and left amygdalae in expression of memory
      for aversively motivated training.
AB  - The present study investigated possible lateralization of amygdala involvement in
      memory for aversively motivated training. Rats with bilateral cannulae aimed at
      the amygdalae were trained in a one-trial inhibitory avoidance task. Twenty-four
      h or 10 days later, animals received bilateral pre-test microinjections of either
      vehicle, 2% lidocaine, or unilateral infusions of each simultaneously. Five min
      after the infusions, retention was tested. Retention latencies of rats given
      bilateral lidocaine or unilateral lidocaine into only the right amygdala were
      significantly lower than controls. These results suggest that the right and left
      amygdalae may make differential contributions to the expression of memory, and
      that the contribution of the right amygdala may be more important to the
      expression of memory for aversively motivated training.

PMID- 7719728
TI  - Enhancement of odorant-induced mucosal activity patterns in rats trained on an
      odorant identification task.
AB  - Previous studies have demonstrated that there are intrinsic spatial patterns of
      odorant sensitivity across the rat olfactory mucosa. The question of how these
      patterns are determined and whether they are modifiable with experience remains
      open. Therefore, the present study examined whether the odorant-induced spatial
      activity patterns which are characteristic of different odorants would be altered
      by experience. Odorant exposure was achieved as a consequence of training and
      testing on a five odorant identification task in which rats were trained to
      differentially report (i.e. identify) the odorants propanol, ehtylacetoacetate,
      carvone, citral, and propyl acetate. At the completion of testing, each animal
      was sacrificed and their mucosal activity patterns recorded using optical
      techniques and a voltage-sensitive dye. Using the dye, di-4-ANEPPS, we monitored
      the fluorescence changes at 100 contiguous sites with a 10 x 10 photodiode array
      on the olfactory mucosa of each rat's septum and medial surface of the turbinates
      in response to the same five odorants. The recorded spatial activity patterns of
      trained animals were compared to those of age-matched controls. For the trained
      animals, both mucosal surfaces showed a significant increase in the average
      response magnitude. Furthermore, for the septal mucosa only, there was a
      significant increase in the distinctiveness of an odorant's characteristic 'hot
      spot'.

PMID- 7719729
TI  - Axons and synapses mediating electrically evoked startle: collision tests and
      latency analysis.
AB  - Davis et al. proposed that the primary acoustic startle reflex is mediated by
      synapses in the ventral cochlear nucleus (VCN), lateral lemniscus (LL) and caudal
      pontine reticular formation (PnC). The collision test was used here to estimate
      the locations of synapses mediating startle-like responses in these sites, and
      the conduction times between and across these synapses. Conditioning (C) and test
      (T) pulses were delivered to pairs of sites in chloral hydrate anaesthetized
      rats, and current thresholds for, and latencies of, hindlimb EMG responses were
      determined. When sites are axonally connected, thresholds increase at the same
      positive and negative C-T intervals ('symmetric collision'), but when sites are
      connected by strong synapses, thresholds increase at asymmetric C-T intervals.
      (i) Asymmetric collisions between VCN and contralateral PnC centered on a C-T
      interval of + 0.5 ms suggest a monosynaptic connection in ventrolateral pons
      (VLP), near LL. (ii) Asymmetric collisions between VCN and contralateral medulla
      centered on a C-T interval of + 0.85 to + 1.0 ms suggest a disynaptic connection.
      (iii) Asymmetric collisions between VLP and ipsilateral medulla centered on a C-T
      interval of 0.2-0.4 ms suggest a monosynaptic connection in PnC, as shown
      previously in freely behaving animals [32]. (4) Symmetric collisions between VLP
      and rostral PnC, and between caudal PnC and medulla suggest fast axonal
      connections. Latency differences between electrode pairs were generally similar
      to collision-derived conduction times. From these, conduction times and
      transmission times were estimated for each axon bundle and synapse in the
      circuit.

PMID- 7719730
TI  - Bone structure and breaking strength in laying hens housed in different husbandry
      systems.
AB  - 1. Bone structure and breaking strength were measured in hens that had been
      housed throughout a laying year in battery cages or in Perchery, Naturel or
      Litter and Wire husbandry systems. 2. Battery caged hens had the poorest bones,
      as assessed by measurements of cancellous bone volume, radiographic density,
      cortical thickness and three-point breaking strength. 3. Humeri from birds in the
      Litter and Wire system were less dense radiographically and weaker than those
      from Perchery or Naturel birds but leg bone characteristics were similar with
      these three systems. 4. There were no differences in bone characteristics between
      birds in Perchery and Naturel systems. 5. There were strong correlations between
      radiographic densities and strengths of contralateral humeri and tibiae over all
      husbandry systems. Humerus structural and strength characteristics may be the
      best criteria of osteoporosis in hens. 6. It is concluded that the extent of
      movement allowed by different husbandry systems affects structural bone loss and
      bone strength in laying hens. 7. It is further concluded that the breaking
      strength of a hen's bone is closely related to morphometric measures and
      radiographic density of its structural components.

PMID- 7719731
TI  - Potential role of serum troponin T in cardiomyocyte injury in the broiler ascites
      syndrome.
AB  - 1. Cardiac troponin T is a recently developed serological marker used as a
      sensitive diagnostic tool for early myocardial damage in 'at risk' human
      patients. 2. Serum troponin T values were measured in young 30-d-old broilers
      with ascites and in healthy age-matched flockmates. 3. The data showed a
      significant increase (P < 0.001) in troponin T values in ascitic broilers
      compared with control birds. A similar increase in the arterial pressure index in
      ascitic birds indicated a good positive correlation at this age. 4. The results
      suggest that this new assay cross-reacts with chicken cardiac troponin T antigen
      and that it may be an important indicator of myocardial cell damage for use in
      future genetic selection programmes in the combat against ascites.

PMID- 7719732
TI  - Simultaneous estimation of variances and covariances using REML and Henderson 3
      in a selected population of White Leghorns.
AB  - 1. Genetic and residual variances and covariances were estimated on performance
      data from 5943 lyaing hens from a 7 generation selection experiment for the
      traits: egg number up to day 270 (EN270), egg weight (EW), body weight at day 215
      (BW), egg mass 100 g of food (EMFC), and residual food consumption (RFC) by a
      Henderson 3 and REML procedure. 2. Simultaneous REML estimates of all 30
      components were obtained by a software package is based on numerical optimisation
      of the log likelihood using a multivariate animal model. Henderson 3 estimates
      were computed on the basis of a hierarchical sire-dam model. Estimates were
      generated beginning with a data set comprising only the first generation, and
      then successively adding one generation after the other. 3. REML estimates for
      heritabilities h2 on the basis of all performance records were 0.40, 0.75, 0.62,
      0.21 and 0.22 for traits EN270, EW, BW, EMFC, and RFC, respectively. The
      corresponding Henderson 3 estimates were: 0.30, 0.57, 0.43, 0.21, and 0.20. 4.
      The results indicate that some REML h2 estimates are substantially different from
      those obtained by Henderson 3 once the data set included three generations as
      opposed to those based on Henderson 3.

PMID- 7719733
TI  - Weight of internal organs and carcase yield of early food restricted broilers
      broilers.
AB  - 1. Effects of food restriction on growth rate and relative growth rates of supply
      organs (liver, heart, lungs and kidneys, digestive tract) and demand organs
      (breast, back, thighs, abdominal fat) of broiler chickens were studied. 2. Birds
      were restricted in intake to 50% (group FI 50) or 75% (group FI 75) of ad libitum
      from 5 to 11 d of age; all birds were fed ad libitum from 12 to 39 d of age. 3.
      Relative growth rates from 12 to 39 d of age of group FI 50 were higher (P <
      0.05) than group FI 75 and control group. 4. No significant differences in food
      conversion ratio, carcase fat and abdominal fat between groups were observed. 5.
      At 12 d of age, relative weight of the empty digestive tract of group FI 50 was
      higher (P < 0.05) than that of the control group and group FI 75. 6. The
      increased weight of the empty digestive tract may have contributed to the ability
      of the chickens to achieve compensatory growth after the restriction period.

PMID- 7719734
TI  - Comparative responses of genetically lean and fat chickens to lysine, arginine
      and non-essential amino acid supply. I. Growth and body composition.
AB  - 1. Three experiments were performed to study the effects of amino acid imbalance
      on the growth of genetically lean (LL) or fat (FL) male chickens from 28 to 42 d
      of age. In experiment 1, five concentrations of digestible lysine were compared
      (4.75, 6.75, 7.75, 8.75 and 9.75 g/kg). In experiment 2, four concentrations of
      digestible arginine were compared (6.53, 7.69, 8.84 and 10.0 g/kg). In experiment
      3, three diets were compared: a high-protein diet (189 g CP/kg), a low-protein
      diet containing added essential amino acids (EAA) (144 g CP/kg) and this low
      protein diet supplemented with 40 g/kg of non-essential amino acids (NEAA)
      (glutamic acid+aspartic acid). 2. LL birds exhibited a lower growth rate than the
      FL when the diet was deficient in either lysine or arginine. Plotting weight gain
      against lysine or arginine intake suggested that most of this effect was caused
      by variations in food intake. 3. When protein gains (body or total proteins) were
      plotted against lysine or arginine intake, LL chickens appeared more efficient
      than FL chickens. 4. Similar growth rates, although slightly lower in FL, were
      obtained with low- and high-protein diets. However, NEAA supplementation of the
      low-protein diet reduced adiposity of LL and did not modify that of FL.
      Increasing crude protein content (all amino acids) was more effective than NEAA
      supplementation in decreasing the adiposity of both lines.

PMID- 7719735
TI  - Comparative responses of genetically lean and fat chickens to lysine, arginine
      and non-essential amino acid supply. II. Plasma amino acid responses.
AB  - 1. Three experiments performed to study the effects of amino acid imbalances on
      the growth of genetically lean (LL) and fat (FL) male chickens from 28 to 42 d of
      age were described by Leclercq et al. (1994). The plasma amino acid
      concentrations of birds on selected treatments from that paper are reported here.
      In experiment 1, three dietary concentrations of digestible lysine were compared
      (4.75, 6.75 and 7.75 g/kg). In experiment 2, two dietary concentrations of
      digestible arginine were compared (6.53 and 10.00 g/kg). In experiment 3, three
      diets were compared: a high-protein diet (189 g CP/kg), a low-protein diet
      containing added essential amino acids (144 g CP/kg), and this low-protein diet
      supplemented with 40 g/kg of non-essential amino acids (NEAA; glutamic and
      aspartic acids). 2. The present results are compared with two earlier reports on
      the same genotypes. The LL consistently had lower plasma concentrations of
      methionine, cystine, phenylalanine, isoleucine and valine, and higher
      concentrations of histidine, than the FL chickens. In 4 of 5 experiments, LL
      leucine concentrations were lower, and glutamic acid, tyrosine, glutamine and
      alanine were higher, than in the FL. The other amino acids measured; arginine,
      lysine, aspartic acid, glycine and serine, exhibited variable responses among the
      experiments. 3. When the limiting essential amino acids, lysine and arginine,
      were added to a deficient diet, the plasma concentration of the supplemented
      amino acid increased while the others remained constant or decreased. 4. When
      glutamic and aspartic acids were added to the low protein diet, plasma amino acid
      responses were similar to those of adding a limiting amino acid to a deficient
      diet, except that alanine exhibited a dramatic increase. 5. Although there were
      genotype by diet interactions for several amino acids, the interactions were
      caused by differences in the degree of the responses, not in their direction. 6.
      These results suggest that the FL and LL genotypes do not utilise various amino
      acids with the same efficiency and, as a consequence, the ideal profile of
      dietary amino acids should not be the same for both lines. The results support
      the hypothesis that selection for fatness and leanness changed the amino acid
      requirements independently of the effects of food intake.

PMID- 7719737
TI  - Effect of dietary phytate on growth and selenium status of chicks fed selenite or
      selenomethionine.
AB  - 1. An experiment was conducted to study the effect of dietary phytate on the
      selenium status of chicks fed on a semi-purified diet with or without supplements
      of sodium selenite or selenomethionine (200 micrograms Selenium/kg). 2.
      Assessment included measurement of growth and activity of glutathione peroxidase
      (GSHPx) (EC.1.11.1.9), an enzyme that limits damage by free radical species
      arising from oxygen metabolism by catalysing the reduction of hydrogen peroxide
      and lipid hydroperoxides. In addition, information was obtained on forms of
      selenium in blood, liver, kidney, heart and muscle, distinguishing between
      selenide-Se, reducible-Se and non-reducible-Se. 3. Phytate caused significant
      reductions in growth, food consumption and food conversion efficiency.
      Supplementary selenium was without effect on growth but significantly increased
      GSHPx activity in all tissues. Phytate also increased GSHPx activity in blood and
      heart, and in muscle in the absence of supplementary selenium, but decreased the
      activity in kidney. 4. Concentrations of all forms of tissue selenium were
      significantly increased by supplementary selenium. In general, there was greater
      deposition from selenomethionine than from selenite and most was in non-reducible
      form. 5. Phytate increased selenium in all tissues except muscle; it is not clear
      if this resulted from increased absorption or increased retention. It increased
      reducible-Se in blood, liver and heart and non-reducible-Se in blood and kidney.
      Tissue concentrations of selenide-Se were highly variable: presence or absence of
      phytate contributed to some significant interactions. 6. The results suggest that
      there is a positive relationship between phytate and selenium status in chicks,
      in contrast to its negative effect on growth.

PMID- 7719736
TI  - A formal method of determining the dietary amino acid requirements of laying-type
      pullets during their growing period.
AB  - 1. The amino acid requirements of laying type pullets during the growing period
      can be estimated by measuring the growth of different components of the body and
      making use of nutritional constants that define the amount of each amino acid
      that is required for the production of the tissues being formed. 2. In this
      experiment, carcase analyses of each of three breeds of pullets were conducted at
      weekly intervals throughout the growth of the pullets, to 18 weeks of age.
      Measurements were made of body weight, gut-fill and feather weight, and chemical
      analyses consisted of water, protein, lipid and ash measurements of both the body
      and the feathers. Each age group comprised 10 birds of each breed. 3. Gompertz
      functions accurately estimated the growth of both body protein and feather
      protein, to 18 weeks of age, from which the rate of growth of these two
      components of the body could be estimated. The mature weight of pullets was
      overestimated by the Gompertz growth curve, which may indicate that a pullet
      ceases to increase in body protein content once sexual maturity has been reached.
      4. Using allometric relationships between the chemical components of the body and
      of feathers, all the components of growth could be estimated from the growth of
      body protein and feather protein. These components were then added together to
      determine the growth rate of the body as a whole. 5. The daily amino acid
      requirements for 4 functions were calculated, namely, those for the maintenance
      of body protein and feather protein, and for the gain in body protein and feather
      protein. These requirements were then summed to determine the requirement of
      pullets on each day of the growing period. 6. Using the 'effective energy'
      system, the amount of energy required by these pullets was calculated for each
      day of the growing period, from which the desired daily food intake of the
      pullets could be predicted. By dividing the amino acid requirement by this daily
      food intake it was possible to determine the concentration of amino acids that
      would be needed in the diet in order to meet the requirements of a pullet. 7. The
      results indicate that the ratio between the requirement for lysine and for
      methionine and cysteine changes dramatically during the growing period, negating
      the concept of a fixed ratio between all the amino acids during growth.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7719738
TI  - Effects of faba bean tannins on the growth and histological structure of the
      intestinal tract and liver of chicks and rats.
AB  - 1. Diets containing a freeze-dried tannin extract from faba beans (Vicia faba L.)
      at concentrations of 0, 8 and 16 g/kg were fed to growing chicks and rats. 2.
      Chicks fed on the tannin-containing diets exhibited a high mortality and
      significant decreases in body-weight as well as lower food intakes and higher
      food intake:weight gain ratios (P < 0.01). In rats there was no mortality but the
      growth and food intake were adversely affected (P < 0.05). 3. Histological
      changes occurred in the ileal mucosa of chicks. Atrophy and shortening of villi
      with distortion of their architecture were observed. Similar histological
      disorders but less pronounced were also found in rats. 4. Histopathology of the
      liver of both chicks and rats showed an hydropic degeneration of hepatocytes,
      clearly more severe in the former than in the latter.

PMID- 7719739
TI  - Relationship of plasma calcium and phosphorus to the shell quality of laying hens
      receiving saline drinking water.
AB  - 1. From 36 to 43 weeks of age 210 White Leghorn laying hens were used to study
      the relationship of plasma calcium and phosphorus concentrations to egg-shell
      quality when saline drinking water was given. 2. Seven experimental treatments in
      which different amounts of sodium chloride were supplied by the food and/or the
      drinking water were compared. 3. Increasing salt intake through the drinking
      water or the food reduced shell thickness and shell calcium, and increased the
      numbers of damaged eggs. Sodium chloride given in the drinking water was more
      effective in reducing shell quality and increasing plasma calcium and phosphorus
      than sodium chloride given in the food.

PMID- 7719740
TI  - Effects of ascorbic acid and 1,25-dihydroxycholecalciferol on alkaline
      phosphatase and tibial dyschondroplasia in broiler chickens.
AB  - 1. The effects of graded amounts of dietary ascorbic acid with or without 10
      micrograms/kg dietary 1,25-dihydroxycholecalciferol on performance, blood and
      bone variables were measured in broiler chicks. 2. 1,25-Dihydroxycholecalciferol
      prevented the tibial dyschondroplasia and rickets caused by feeding a low calcium
      diet. Gain:food was decreased, but body weight was not affected by feeding 10
      micrograms/kg 1,25-dihydroxycholecalciferol. Phytate phosphorus retention was
      increased by dietary 1,25-dihydroxycholecalciferol. 3. Dietary ascorbic acid did
      not influence the incidence of tibial dyschondroplasia, but did reduce the
      incidence of rickets at a dietary concentration of 250 mg/kg. Gain:food was
      increased when 250 or 500 mg ascorbic acid/kg diet were added along with 10
      micrograms/kg 1,25-dihydroxycholecalciferol in one of two experiments. 4.
      Alkaline phosphatase activity and plasma 1,25-dihydroxycholecalciferol were not
      affected by the dietary treatments. Plasma 25-hydroxycholecalciferol
      concentration was decreased by dietary 1,25-dihydroxycholecalciferol. 5. Ascorbic
      acid had no synergistic effects with 1,25-dihydroxycholecalciferol on the blood
      and bone variables investigated in broiler chickens at the dietary concentrations
      of 1,25-dihydroxycholecalciferol used in this work.

PMID- 7719741
TI  - Development and validation of a homologous radioimmunoassay using a biologically
      active recombinant turkey prolactin.
AB  - 1. A new homologous radioimmunoassay has been developed for the measurement of
      turkey prolactin. 2. A 25000 kDa purified recombinant derived turkey prolactin
      (rtPRL), the biological activity of which was tested using a crop sac assay, was
      used as immunogen for the production of rabbit antiserum. In this biological
      test, the rtPRL was as active as the ovinePRL. 3. The radioligand (rtPRL) was
      labelled with 125I and the assay allowed the detection of standard doses of rtPRL
      ranging from 400 pg/tube to 50 ng/tube. 4. No cross reaction with chicken
      luteinising hormone and recombinant chicken growth hormone was detected. 5. The
      within and between assay coefficients of variability were 5.0 +/- 2.7% and 16.3%,
      respectively. The overall mean recovery ratio was 1.01. 6. The dose-response
      curves obtained with serial dilution of plasma and pituitary from turkey hens at
      different physiological stages and from male turkeys were parallel to those
      obtained with standard rtPRL. 7. The measured concentration of prolactin was 5
      times higher in plasma from incubating than laying turkey hens, and the
      pituitaries from incubating hens contained 2 and 4 times more prolactin than
      those of laying and out of lay hens or males, respectively. 8. To further assess
      the validity of the assay, we measured changes in plasma concentration of
      prolactin in turkeys following stimulation with chicken vasointestinal peptide
      (cVIP). A single injection of 1 or 10 micrograms/kg body weight of cVIP to laying
      hens produced a large and rapid increase in plasma prolactin. 9. This new
      radioimmunoassay appears to be high for the measurement of turkey prolactin.

PMID- 7719742
TI  - Effects of dietary corticosterone and trilostane on growth and skeletal muscle
      protein turnover in broiler cockerels.
AB  - 1. The effects of dietary corticosterone and trilostane, an inhibitor of
      glucocorticoid synthesis, on: growth, rates of synthesis and breakdown of
      skeletal muscle protein, and content of abdominal fat were studied in broiler
      chickens. 2. Dietary corticosterone (5, 10 or 20 mg/kg) depressed body weight
      gain and increased abdominal fat content in a dose-dependent manner while dietary
      trilostane (1.4 or 7.0 mg/kg) had no effect. 3. The rate of protein breakdown in
      skeletal muscle estimated from N tau-methylhistidine excretion was increased in a
      dose-dependent manner by dietary corticosterone but it was decreased by
      trilostane. 4. The rate of skeletal muscle protein synthesis was not affected by
      corticosterone although it was decreased by trilostane. 5. Plasma corticosterone
      concentration was increased in a dose-dependent manner by dietary corticosterone
      and decreased by treatment with 7 mg trilostane/kg diet. 6. The results indicate
      that higher concentrations of plasma corticosterone increase protein breakdown in
      skeletal muscle but do not affect muscle protein synthesis while both the rates
      of synthesis and breakdown are decreased when plasma corticosterone concentration
      is reduced.

PMID- 7719743
TI  - Haematology and blood composition at two ambient temperatures in genetically fat
      and lean adult broiler breeder females fed ad libitum or restricted throughout
      life.
AB  - 1. Genetically fat and lean adult broiler breeder females were fed ad libitum or
      restricted throughout life. At one year of age, comparisons of blood viscosity
      and haematology and changes in blood chemistry after exposure to thermal stress
      were conducted. 2. Whole blood viscosity was more than twice as high, and plasma
      triglyceride and haemoglobin concentrations were over 30% higher in fat line than
      in lean line females fed ad libitum or in restricted birds of both genotypes. 3.
      Mean cell haemoglobin concentration was higher and mean cell volume lower in fat
      compared with lean line females. 4. Food restriction was associated with lower
      plasma triglyceride concentrations, lower numbers of heterophils and monocytes
      and a lower heterophil-lymphocyte ratio. 5. Fat line birds had a higher blood
      pCO2 and lower pH than lean line birds. 6. Thermal stress was associated in ad
      libitum-fed birds with a rise in blood pH and a decrease in pCO2, and in
      restricted birds with a decline in blood pH and an increase in pCO2. 7. Blood
      creatine kinase activity increased in all groups under thermal stress.

PMID- 7719744
TI  - Use of rice husk litter at different depths for broiler chicks during summer.
AB  - 1. Four groups of 36 one-day-old broiler chicks were reared for 8 weeks during
      summer on rice husk litter spread to depths of 20, 30, 40 or 50 mm. 2. The depth
      of the litter did not significantly affect live weight gain, food consumption,
      food conversion ratio, liveability or production number. 3. It was concluded that
      rice husks can be used as litter at depths of between 20 and 50 mm during summer
      to raise broilers without affecting performance.

PMID- 7719745
TI  - Keep in the best of health: a mother's guide to a healthy pregnancy.

PMID- 7719746
TI  - Supporting women in labour: the doula's role.
AB  - A doula is a woman without medical experience who guides and assists a new mother
      in childbirth and babycare tasks. The doula's role is to hold the woman, breathe
      with her, smile at her and provide encouragement and reassurance. Doula support
      for the labouring woman may reduce catecholamine levels, thus shortening the
      duration of labour. Doula support can increase self-esteem in the labouring woman
      and facilitate her transition to motherhood. Rates of oxytocin augmentation,
      epidural anaesthesia and caesarean section can be reduced by doula support.
      Fathers may find it hard to provide doula-type support during labor because of
      their own emotional involvement in the birth. The introduction of doulas into
      labour wards could lead to reduced costs for maternity services.

PMID- 7719747
TI  - Changing mothers' smoking behaviour.

PMID- 7719748
TI  - Weaning: COMA report recommendations.

PMID- 7719749
TI  - Types and causes of miscarriage.

PMID- 7719750
TI  - Lavender oil and perineal repair.
AB  - The study examined the practice of adding six drops of pure lavender oil to bath
      water daily for 10 days following childbirth to reduce perineal discomfort.
      Mothers using the oil found it pleasant to use, and there were no side effects.
      The pattern of discomfort scores shows no statistical differences between groups.
      Those using lavender oil showed lower mean discomfort scores, particularly
      between days 3 and 5. Further studies might explore the effect of varying the
      amount of oil used or changing the mode of application.

PMID- 7719751
TI  - Complementary therapy and the mother's wishes.
AB  - Midwives cannot ignore the growing interest from clients who wish to use
      complementary therapies. However, midwives have a duty to ensure that their
      clients are aware of the advantages and the dangers of particular therapies. Co
      operation with complementary therapists is to be encouraged, but the midwife must
      never delegate responsibility for her client. Managers should arrange for
      midwives to receive training in particularly complementary therapies, so that
      midwives may widen the scope of their professional practice. Midwives whose
      clients request complementary therapies may find themselves asked to provide
      hypnotism, aromatherapy or another therapy that may conflict with the accepted
      standards of midwifery practice. A mother might also wish to use homeopathic
      remedies for an underlying condition.

PMID- 7719752
TI  - Home birth in question.

PMID- 7719753
TI  - Foreign bodies.

PMID- 7719754
TI  - Strategies to promote preterm breastfeeding.
AB  - A breastfeeding support programme based on the principles of normal lactation has
      been adapted to meet the needs of women and their premature or sick infants. The
      four specific areas are: the initiation and maintenance of lactation in-hospital
      breastfeeding growth and development transfer management. This approach has
      indicated substantial physiological and psychological benefits for mothers, and
      clear possibilities of maximising preterm infant growth.

PMID- 7719755
TI  - The JIM interview. Samuel O. Thier, MD.
AB  - Although the public has grown increasingly accustomed to consolidation in the
      health care industry, the announcement on December 8, 1993, that the
      Massachusetts General Hospital (MGH) and the Brigham and Women's Hospital would
      merge merited front page coverage across the nation. These hospitals, long
      considered the crown jewels of the Harvard Medical School, have a history rich in
      tradition and a reputation for fierce independence. The merged entity,
      subsequently named Partners Healthcare System, Inc., has a payroll of 17,500
      employees, making it the largest employer in Boston and the third largest in
      Massachusetts. Shortly after the merger, Boston newspapers reported that the
      announced plan had circumvented plans for Harvard to merge all five of its major
      teaching hospitals. The MGH-Brigham merger included no provisions for the other
      three Harvard-affiliated hospitals, the Massachusetts Deaconess, the Beth Israel,
      or the Dana Farber Cancer Institute. Speculation that the move was accomplished
      with little input from Harvard Medical School Dean Daniel Tosteson further
      accentuated the delicate politics of the merger. To run this powerhouse of health
      care, teaching, and research, the directors of Partners turned to Dr. Samuel O.
      Thier. Thier, who had honed his leadership skills as Medicine Chairman at Yale
      and President of the Institute of Medicine (IOM), has lifelong ties to the MGH.
      Indeed during his recent tenure as President of Brandeis University, he still
      made rounds at the hospital. Largely credited with revitalizing the IOM and
      restoring financial health to Brandeis, Thier must now lead an entity playing in
      a quickly changing and unpredictable marketplace.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7719756
TI  - Coronary artery bypass surgery: risks and benefits, realistic and unrealistic
      expectations.

PMID- 7719757
TI  - Cytokines in rheumatoid arthritis.

PMID- 7719758
TI  - The formation and biologic significance of phagocyte-derived oxidants.

PMID- 7719759
TI  - A novel approach to the development of anti-inflammatory agents: adenosine
      release at inflamed sites.

PMID- 7719760
TI  - Interferon gamma modulates the expression of neutrophil-derived chemokines.
AB  - Specific cell recruitment to a site of acute inflammation is a crucial event
      characterized by the elicitation of mainly polymorphonuclear neutrophils (PMNs).
      Recently, it has been reported that PMNs can express and secrete chemotactic
      cytokines or chemokines, including IL-8, MIP-1 alpha, and MIP-1 beta. Moreover,
      PMN-derived chemokines are regulated by various soluble mediators, such as
      dexamethasone, prostaglandin E, classic chemoattractant factors (e.g., fMLP, C5a,
      leukotriene B4), IL-4, and IL-10. In this article we demonstrate that PMNs
      treated with IFN-gamma, a Th1-derived cytokine, can inhibit early mRNA expression
      for MIP-1 alpha, MIP-1 beta, and IL-8 (up to 8 hours post IFN-gamma addition),
      while augmenting their production at 24 hours post IFN-gamma addition.
      Furthermore, our studies demonstrate that one of the mechanisms for the activity
      of IFN-gamma in this system is via the autocrine activity of TNF-alpha. These
      data imply that PMN-derived chemokines are regulated by not only proinflammatory
      cytokines, including IL-1 beta and TNF-alpha, but also Th1- and Th2-derived
      cytokines, including IL-4, IL-10, and IFN-gamma. The role of these cytokine
      networks in regulating PMN-derived chemokines may play an important role in
      leukocyte elicitation during the initiation and maintenance of an inflammatory
      response.

PMID- 7719761
TI  - The effects of corticosteroids on lymphocyte recirculation in humans: analysis of
      the mechanism of impaired lymphocyte migration to lymph node following
      methylprednisolone administration.
AB  - BACKGROUND: Steroid therapy profoundly inhibits lymphocyte migration into lymph
      nodes (LN), thereby disrupting lymphocyte recirculation. This study was
      undertaken in human subjects to examine two nonmutually exclusive hypotheses
      proposed to explain this steroid effect: (1) steroids decrease the capacity of LN
      high endothelial venules (HEV) to support lymphocyte adherence; and/or (2)
      steroids alter the expression of lymphocyte adhesion molecules specific for entry
      into LNs. METHODS: Human LNs were obtained from cadaveric organ donors before and
      after methylprednisolone infusion and examined for their capacity to support
      lymphocyte adherence using an in vitro lymphocyte-HEV adherence assay.
      Additionally, six healthy volunteers underwent infusions of saline (placebo) and
      methylprednisolone (3 mg/kg in saline), and peripheral blood lymphocytes were
      isolated before, immediately after, and at 1, 2, 4, 8, 24, and 48 hours following
      infusions. At each timepoint, flow cytometric analysis of lymphocyte L-selectin,
      CD44, and LFA-1 expression was assessed. Short-term tissue culture studies were
      also performed to examine the direct effects of steroids on the expression of
      these lymphocyte proteins. RESULTS: LNs obtained from organ donors before and
      after steroid infusion displayed no differences in the capacity of HEV to support
      lymphocyte adherence. In controlled steroid infusion studies, lymphopenia was
      observed within 1 hour and persisted for 8 hours. Cells isolated during the
      period of lymphopenia did not adhere to LN HEV, and there was a marked decrease
      in both the percentage and mean fluorescence intensity level of L-selectin+
      lymphocytes; minor changes were observed in the percentage of CD44+ and LFA-1+
      cells, while the mean fluorescence intensity level decreased for CD44+ cells and
      increased for LFA-1+ cells. All such changes in adhesion protein levels among
      circulating cells reversed with the resolution of lymphopenia. However, in tissue
      culture experiments, steroids did not alter the expression of lymphocyte adhesion
      proteins. CONCLUSIONS: The decreased migration of lymphocytes to LN following
      steroid administration is not due to changes in the capacity of HEV to bind
      lymphocytes, but results from decreases in the level of L-selectin expressed
      among circulating cells. Culture studies suggest that steroids do not directly
      alter lymphocyte adhesion protein expression. The possibility that these agents
      act indirectly by stimulating the release and/or promoting the activity of
      relevant biologic mediators affecting lymphocyte adhesion protein expression
      needs further exploration.

PMID- 7719762
TI  - Bilateral osteochondritis dissecans in a female pitcher. A case report and review
      of the literature.

PMID- 7719763
TI  - Psychomotor education in orthopaedics: a reconsideration.

PMID- 7719764
TI  - A randomized clinical trial comparing cemented to cementless total hip
      replacement in 250 osteoarthritic patients: the impact on health related quality
      of life and cost effectiveness.

PMID- 7719765
TI  - The prevalence and natural history of early osteonecrosis (ON) of the femoral
      head.
AB  - We performed limited MRI exams of the hips of renal transplant patients to
      determine the prevalence of osteonecrosis (ON) and the natural history of early
      lesions. Of 132 subjects, ten patients and 15 hips were considered positive for
      ON (prevalence = 7.6%, bilaterality = 50%). Eleven of the MRI-positive hips were
      Ficat Stage 0 (asymptomatic, pre-radiographic) and were followed with serial
      radiographs and MRI exams. With an average follow-up of 22 months, only one of
      these early lesions progressed beyond Ficat 0. The other ten hips neither
      developed progressive MRI changes nor progressed to radiographic stages. Although
      our follow-up of 22 months is short, the results suggest that early ON may have a
      benign course in many cases. This supports the recent work of Kopecky et al., who
      found that many early lesions in renal transplant patients seemingly stabilize or
      disappear. While the prevalence was lower than in some previous reports, a
      significant number of patients did demonstrate previously unsuspected disease.
      Given the recent reports of poor results and high complication rates using
      "prophylactic" surgery such as core decompression for early ON, we recommend
      further study into the natural history of these lesions to assess the need for
      such procedures. In addition, we describe the use of a simple, quick and cost
      effective method to screen high risk patients for early ON.

PMID- 7719766
TI  - Bilateral humeral head osteonecrosis following spinal cord injury: a case report
      illustrating the importance of adhering to the recommendations of the Second
      National Acute Spinal Cord Injury Study.
AB  - Five years prior to the 1990 publication of the Second National Acute Spinal Cord
      Injury Study (SNASCIS), a 24-year-old man sustained traumatic paraplegia, and was
      treated with 797 mg of dexamethasone over the ensuing 26 days. Within three years
      he developed symptomatic bilateral humeral head osteonecrosis. Although his total
      steroid dose was less than one-third of the comparable dose recommended by the
      SNASCIS, the duration of administration of the steroid was much longer. This case
      illustrates the importance of adhering to the guidelines established by the
      SNASCIS, especially regarding the 24-hour administration period.

PMID- 7719767
TI  - The effects of space flight on the composition of the intervertebral disc.
AB  - The lumbar annuli of rats flown on a COSMOS space flight were compared with those
      of three control groups and a ground antigravity tail suspension model. The wet
      and dry weights of the space flight annuli were significantly smaller than the
      three control groups. In addition, the collagen-to-proteoglycan ratio was
      significantly greater in the flight group due to a proportional increase in
      collagen and a decrease in proteoglycan. Finally, it appears microgravity may
      have altered the nature of the proteoglycan population as more proteoglycans
      leached from the annuli of flight animals than control animals when immersed in
      water.

PMID- 7719768
TI  - The effects of immobilization on the maturation of the anterior cruciate ligament
      of the rabbit knee.
AB  - Immobilization-induced alterations occurred in young anterior cruciate ligament
      (ACL) samples, including the loss of the rounded appearance of the cells. The
      mature ACL was minimally altered by immobilization at the light microscopy level.
      In the immobilized young ACL the fibroblasts became elongated and there was loss
      of the normal pericellular matrix. The immobilized mature ACL differed from
      controls primarily in the intracellular composition, as there was significantly
      more rough endoplasmic reticulum (RER) present. Collagen concentrations were
      reduced only in young immobilized ACL, while no differences were observed in the
      mature ACL. The collagen synthesis rate in the mature ACL increased with
      immobilization, although no significant change was observed in the young ACL. The
      increase in the rate of synthesis of the stress deprived ACL in the mature
      animals reflected an increase in collagen turnover rather than an increase in
      accumulation of collagen.

PMID- 7719769
TI  - The use of thermography in sympathetically maintained pain.
AB  - This paper reviews the symptomatology, pathophysiology, and treatment of reflex
      sympathetic dystrophy and sympathetically maintained pain. It is the author's
      experience that there exists a group of patients who present with chronic,
      unexplained pain following trauma, but lack the physical findings and positive
      investigative tests to confirm the diagnosis of reflex sympathetic dystrophy. For
      these patients, thermography serves as a useful and sensitive test to diagnosis
      sympathetically maintained pain. This paper presents six case reports in which
      thermography was used to diagnosis sympathetic dysfunction as the cause of
      chronic pain.

PMID- 7719770
TI  - Stabilization procedures of the hindfoot.

PMID- 7719771
TI  - A hamartomatous joint mimicking dysplasia epiphysealis hemimelica of the talus.

PMID- 7719772
TI  - An environmental hazard to the diabetic foot. A case report.

PMID- 7719773
TI  - If the shoe fits,....

PMID- 7719774
TI  - Adrian E. Flatt--surgeon and scholar.

PMID- 7719776
TI  - Post-burn heterotopic ossification at the elbow.

PMID- 7719775
TI  - Application of multiplanar ligamentotaxis to external fixation of distal radius
      fractures.

PMID- 7719777
TI  - Chronic perilunate fracture dislocations and primary proximal row caprectomy.

PMID- 7719778
TI  - The "don't operate on me" sign.

PMID- 7719779
TI  - Anterior labrum reconstruction with mini-capsular shift procedure.
AB  - An anterior labrum reconstruction and mini-capsular shift (ARMS) procedure was
      performed in 64 patients (69 shoulders) with traumatic anterior or anterior
      inferior glenohumeral instability between 1984 and 1990. Sixty-three of the sixty
      nine stabilizations were performed for recurrent dislocation and six were
      performed for recurrent subluxation. Eighty-eight percent of the patients (61
      shoulders) were available for clinical follow-up at an average of 36 months
      (range 28-78). There were 44 males and 12 females with an average age of 28 years
      (range 15-46). Excellent range of motion was recorded at follow-up for the
      operated shoulder with an average of 180 degrees of forward elevation, 72 degrees
      of external rotation with the arm at the side, 92 degrees of external rotation
      with the arm in the 90 degree abducted position and 90 degrees of internal
      rotation with the arm in the 90 degree abducted position. The range of motion of
      the normal shoulder was 180 degrees, 76 degrees, 101 degrees and 94 degrees
      respectively. Utilizing the rating scale from the American Shoulder and Elbow
      Society, pain improved from 3.1 to 4.4, stability improved from 1.1 to 4.5, and
      function improved from 2.5 to 3.8 on the average. Subjective rating revealed 95%
      of the patients to be satisfied with the operative procedure. According to the
      criteria of Rowe et al, 90% of the results were good or excellent. Five patients
      (8%) suffered a recurrent dislocation at an average of 32 months after the
      surgery. Four resulted from significant trauma (6%). One patient (2%) complained
      of a single episode of subluxation during early recovery. Two patients required
      shoulder manipulations to improve motion. No other complications occurred. The
      patients reviewed in this study were actively involved in sports. The majority of
      pre- and postoperative Tegner ratings exceeded 7.0.

PMID- 7719780
TI  - MRI of tendon injuries.

PMID- 7719781
TI  - Sports fractures.
AB  - Fractures occur in athletes and dramatically influence performance during
      competitive and recreational activities. Fractures occur in athletes as the
      result of repetitive stress, acute sports-related trauma and trauma outside of
      athletics. The literature provides general guidelines for treatment as well as a
      variety of statistics on the epidemiology of fractures by sport and level of
      participation. Athletes are healthy and motivated patients, and have high
      expectations regarding their level of function. These qualities make them good
      surgical candidates. Although closed treatment methods are appropriate for most
      sports fractures, an aggressive approach to more complicated fractures employing
      current techniques may optimize their subsequent performance.

PMID- 7719782
TI  - Popliteus function in ACL-deficient patients.
AB  - Anterior cruciate ligament (ACL) injuries commonly result in anterolateral
      instability, resulting in a "pivot shift" phenomenon. Given that popliteus muscle
      stimulation results in a pivot shift, others have postulated that the popliteus
      muscle has a role in the pivot shift phenomenon. We hypothesized that patients
      with instability from ACL injuries may have excessive popliteus muscle activity.
      Therefore, we studied the EMG activity (using fine wire electrodes) of the
      popliteus muscle in sixteen normal subjects and ten ACL-deficient subjects. We
      recorded the EMG in six activities (level walking and jogging, ascending walking
      and jogging, and descending walking and jogging). Person's Product Moment
      Correlations were above 0.7, except in the case of ascending the treadmill (r =
      0.427) and ascending jogging (r = 0.645), suggesting that the timing of the
      signals was similar for injured and uninjured limbs. Variance ratios for the
      injured and uninjured limbs were statistically similar, suggesting similar
      variability of patterns. Thus, we observed only minor popliteus EMG signal
      differences in this group of patients. We conclude that the popliteus muscle does
      not contribute to instability in the studied activities.

PMID- 7719783
TI  - Management of chronic posterolateral instability of the knee: operative technique
      for the posterolateral corner sling procedure.

PMID- 7719784
TI  - Standards for medical identifiers, codes, and messages needed to create an
      efficient computer-stored medical record. American Medical Informatics
      Association.
AB  - A major obstacle to establishing a computer-stored medical record is the lack of
      "standards" that would permit government, care providers, insurance companies,
      and medical computer system developers to share patient data easily. In this
      position paper, the Board of Directors of the American Medical Informatics
      Association recommends specific approaches to standardization in the areas of
      patient, provider, and site of care identifiers; computerized health care message
      exchange; medical record content and structure, and medical codes and
      terminologies. The key concept developed in this position paper is that
      developers and users of computer-stored medical records must embrace existing and
      tested approaches, despite their imperfections, to progress quickly. This
      approach to standardization is being coordinated with the American National
      Standards Institute's Health Informatics Standards Planning Panel. The
      development of standards is a long-term process involving continued refinement.
      The proposed standards are an important step toward the goal of better and more
      efficient health care.

PMID- 7719785
TI  - Designing medical informatics research and library--resource projects to increase
      what is learned.
AB  - Careful study of medical informatics research and library-resource projects is
      necessary to increase the productivity of the research and development
      enterprise. Medical informatics research projects can present unique problems
      with respect to evaluation. It is not always possible to adapt directly the
      evaluation methods that are commonly employed in the natural and social sciences.
      Problems in evaluating medical informatics projects may be overcome by
      formulating system development work in terms of a testable hypothesis;
      subdividing complex projects into modules, each of which can be developed, tested
      and evaluated rigorously; and utilizing qualitative studies in situations where
      more definitive quantitative studies are impractical.

PMID- 7719786
TI  - Knowledge-based approaches to the maintenance of a large controlled medical
      terminology.
AB  - OBJECTIVE: Develop a knowledge-based representation for a controlled terminology
      of clinical information to facilitate creation, maintenance, and use of the
      terminology. DESIGN: The Medical Entities Dictionary (MED) is a semantic network,
      based on the Unified Medical Language System (UMLS), with a directed acyclic
      graph to represent multiple hierarchies. Terms from four hospital systems
      (laboratory, electrocardiography, medical records coding, and pharmacy) were
      added as nodes in the network. Additional knowledge about terms, added as
      semantic links, was used to assist in integration, harmonization, and automated
      classification of disparate terminologies. RESULTS: The MED contains 32,767 terms
      and is in active clinical use. Automated classification was successfully applied
      to terms for laboratory specimens, laboratory tests, and medications. One benefit
      of the approach has been the automated inclusion of medications into multiple
      pharmacologic and allergenic classes that were not present in the pharmacy
      system. Another benefit has been the reduction of maintenance efforts by 90%.
      CONCLUSION: The MED is a hybrid of terminology and knowledge. It provides domain
      coverage, synonymy, consistency of views, explicit relationships, and multiple
      classification while preventing redundancy, ambiguity (homonymy) and
      misclassification.

PMID- 7719787
TI  - A performance and failure analysis of SAPHIRE with a MEDLINE test collection.
AB  - OBJECTIVE: Assess the performance of the SAPHIRE automated information retrieval
      system. DESIGN: Comparative study of automated and human searching of a MEDLINE
      test collection. MEASUREMENTS: Recall and precision of SAPHIRE were compared with
      those attributes of novice physicians, expert physicians, and librarians for a
      test collection of 75 queries and 2,334 citations. Failure analysis assessed the
      efficacy of the Metathesaurus as a concept vocabulary; the reasons for retrieval
      of nonrelevant articles and nonretrieval of relevant articles; and the effect of
      changing the weighting formula for relevance ranking of retrieved articles.
      RESULTS: Recall and precision of SAPHIRE were comparable to those of both
      physician groups, but less than those of librarians. CONCLUSION: The current
      version of the Metathesaurus, as utilized by SAPHIRE, was unable to represent the
      conceptual content of one-fourth of physician-generated MEDLINE queries. The most
      likely cause for retrieval of nonrelevant articles was the presence of some or
      all of the search terms in the article, with frequencies high enough to lead to
      retrieval. The most likely cause for nonretrieval of relevant articles was the
      absence of the actual terms from the query, with synonyms or hierarchically
      related terms present instead. There were significant variations in performance
      when SAPHIRE's concept-weighing formulas were modified.

PMID- 7719788
TI  - Terms used by nurses to describe patient problems: can SNOMED III represent
      nursing concepts in the patient record?
AB  - OBJECTIVE: To analyze the terms used by nurses in a variety of data sources and
      to test the feasibility of using SNOMED III to represent nursing terms. DESIGN:
      Prospective research design with manual matching of terms to the SNOMED III
      vocabulary. MEASUREMENTS: The terms used by nurses to describe patient problems
      during 485 episodes of care for 201 patients hospitalized for Pneumocystis
      carinii pneumonia were identified. Problems from four data sources (nurse
      interview, intershift report, nursing care plan, and nurse progress
      note/flowsheet) were classified based on the substantive area of the problem and
      on the terminology used to describe the problem. A test subset of the 25 most
      frequently used terms from the two written data sources (nursing care plan and
      nurse progress note/flowsheet) were manually matched to SNOMED III terms to test
      the feasibility of using that existing vocabulary to represent nursing terms.
      RESULTS: Nurses most frequently described patient problems as signs/symptoms in
      the verbal nurse interview and intershift report. In the written data sources,
      problems were recorded as North American Nursing Diagnosis Association (NANDA)
      terms and signs/symptoms with similar frequencies. Of the nursing terms in the
      test subset, 69% were represented using one or more SNOMED III terms.

PMID- 7719789
TI  - JAMIA--why?

PMID- 7719790
TI  - Dehumanization of patient care--are computers the problem or the solution?

PMID- 7719791
TI  - Development of medical informatics standards.

PMID- 7719793
TI  - Computer-based physician order entry: the state of the art.
AB  - Direct computer-based physician order entry has been the subject of debate for
      over 20 years. Many sites have implemented systems successfully. Others have
      failed outright or flirted with disaster, incurring substantial delays, cost
      overruns, and threatened work actions. The rationale for physician order entry
      includes process improvement, support of cost-conscious decision making, clinical
      decision support, and optimization of physicians' time. Barriers to physician
      order entry result from the changes required in practice patterns, roles within
      the care team, teaching patterns, and institutional policies. Key ingredients for
      successful implementation include: the system must be fast and easy to use, the
      user interface must behave consistently in all situations, the institution must
      have broad and committed involvement and direction by clinicians prior to
      implementation, the top leadership of the organization must be committed to the
      project, and a group of problem solvers and users must meet regularly to work out
      procedural issues. This article reviews the peer-reviewed scientific literature
      to present the current state of the art of computer-based physician order entry.

PMID- 7719794
TI  - Medicare charges and the operational-year coding concept.
AB  - The introduction by the Health Care Financing Administration, in 1993, of
      separate conversion factors for "medical" and "surgical" services to be used in
      calculating Medicare charges would ordinarily necessitate the use of year
      specific software source code. By designing the system to utilize macro
      substitution of the year in the names of Current Procedural Terminology for
      Physicians Code databases, database fields, and system variables, it is possible
      to calculate Medicare charges without annually rewriting source code. Once such a
      system is in place, simply by changing the operational year, the correct data and
      means of computation are automatically available.

PMID- 7719795
TI  - Evaluation of a new method for cardiovascular reasoning.
AB  - OBJECTIVE: Evaluate the accuracy of the detailed diagnostic reasoning of the
      Heart Failure Program incorporating a new mechanism to handle temporal
      relationships and severity constraints. DESIGN: Tools were developed to summarize
      diagnoses and automatically generate evaluation forms. Five expert cardiologists
      were asked to review the reasoning of the program, with two analyzing each case.
      Cases were gathered retrospectively for diversity and difficulty and 26 randomly
      selected cases were evaluated. The underlying issues were identified and
      classified. RESULTS: Both reviewers rated the first diagnosis correct in 25% of
      the cases and at least one rated it wrong in 10%. Analyzing the detailed
      reasoning, 137 issues were raised, about 5.3 per case. Of these, 53% were
      possible concerns raised by one reviewer. Of the 5.3 issues per case, 2.5 were
      attributable to controversies, misunderstandings, or mistakes; 1 was due to the
      overly simplistic representation of the summaries; and 1.8 were issues related to
      the program. CONCLUSION: Overall, the program is capable of providing high
      quality detailed diagnostic hypotheses for complex cardiovascular cases. The
      results highlight several issues: 1) the difficulty of effectively summarizing
      hypotheses, 2) the nature of a physician's causal explanation, and 3) some
      problems in evaluating detailed diagnostic reasoning. The mistakes the program
      made imply that some additional refinement is needed but that the reasoning
      mechanisms developed can support the appropriate reasoning. The appropriate next
      step is a prospective evaluation addressing the program's usefulness.

PMID- 7719792
TI  - Medical diagnostic decision support systems--past, present, and future: a
      threaded bibliography and brief commentary.
AB  - Articles about medical diagnostic decision support (MDDS) systems often begin
      with a disclaimer such as, "despite many years of research and millions of
      dollars of expenditures on medical diagnostic systems, none is in widespread use
      at the present time." While this statement remains true in the sense that no
      single diagnostic system is in widespread use, it is misleading with regard to
      the state of the art of these systems. Diagnostic systems, many simple and some
      complex, are now ubiquitous, and research on MDDS systems is growing. The nature
      of MDDS systems has diversified over time. The prospects for adoption of large
      scale diagnostic systems are better now than ever before, due to enthusiasm for
      implementation of the electronic medical record in academic, commercial, and
      primary care settings. Diagnostic decision support systems have become an
      established component of medical technology. This paper provides a review and a
      threaded bibliography for some of the important work on MDDS systems over the
      years from 1954 to 1993.

PMID- 7719796
TI  - Natural language processing and the representation of clinical data.
AB  - OBJECTIVE: Develop a representation of clinical observations and actions and a
      method of processing free-text patient documents to facilitate applications such
      as quality assurance. DESIGN: The Linguistic String Project (LSP) system of New
      York University utilizes syntactic analysis, augmented by a sublanguage grammar
      and an information structure that are specific to the clinical narrative, to map
      free-text documents into a database for querying. MEASUREMENTS: Information
      precision (I-P) and information recall (I-R) were measured for queries for the
      presence of 13 asthma-health-care quality assurance criteria in a database
      generated from 59 discharge letters. RESULTS: I-P, using counts of major errors
      only, was 95.7% for the 28-letter training set and 98.6% for the 31-letter test
      set. I-R, using counts of major omissions only, was 93.9% for the training set
      and 92.5% for the test set.

PMID- 7719797
TI  - A general natural-language text processor for clinical radiology.
AB  - OBJECTIVE: Development of a general natural-language processor that identifies
      clinical information in narrative reports and maps that information into a
      structured representation containing clinical terms. DESIGN: The natural-language
      processor provides three phases of processing, all of which are driven by
      different knowledge sources. The first phase performs the parsing. It identifies
      the structure of the text through use of a grammar that defines semantic patterns
      and a target form. The second phase, regularization, standardizes the terms in
      the initial target structure via a compositional mapping of multi-word phrases.
      The third phase, encoding, maps the terms to a controlled vocabulary. Radiology
      is the test domain for the processor and the target structure is a formal model
      for representing clinical information in that domain. MEASUREMENTS: The
      impression sections of 230 radiology reports were encoded by the processor.
      Results of an automated query of the resultant database for the occurrences of
      four diseases were compared with the analysis of a panel of three physicians to
      determine recall and precision. RESULTS: Without training specific to the four
      diseases, recall and precision of the system (combined effect of the processor
      and query generator) were 70% and 87%. Training of the query component increased
      recall to 85% without changing precision.

PMID- 7719798
TI  - Toward data standards for clinical nursing information.
AB  - OBJECTIVE: Develop standard terms and codes for recording nursing care
      information in patient records to permit relevant data to be abstracted into a
      shared database for effectiveness research. DESIGN: A collaborative effort by the
      University of Virginia, Thomas Jefferson University Hospital, and the University
      Hospital Consortium to develop a set of terms to represent specific examples of
      nursing diagnoses/patient care problems, nursing interventions/patient care
      activities, and patient outcomes. Terms found in standards of care are being
      compiled, classified, and coded. RESULTS: Standard terminology and codes have
      been developed for 209 nursing diagnoses/patient care problems, 122 expected
      patient outcomes, and 545 interventions/patient care activities. The terms come
      from five nursing units in one hospital and from two units in a second hospital.
      Preliminary findings suggest that in the specialty areas for which terms have
      been developed, the terms are adequate to capture these types of nursing data in
      the patient record.

PMID- 7719800
TI  - Lessons from the origins of informatics.

PMID- 7719799
TI  - Client-server, distributed database strategies in a health-care record system for
      a homeless population.
AB  - OBJECTIVE: To design and develop a computer-based health-care record system to
      address the needs of the patients and providers of a homeless population. DESIGN:
      A computer-based health-care record system being developed for Boston's
      Healthcare for the Homeless Program (BHCHP) uses client-server technology and
      distributed database strategies to provide a common medical record for this
      transient population. The differing information requirements of physicians,
      nurses, and social workers are specifically addressed in the graphic application
      interface to facilitate an integrated approach to health care. This computer
      based record system is designed for remote and portable use to integrate smoothly
      into the daily practice of providers of care to the homeless. The system uses
      remote networking technology and regular phone lines to support multiple
      concurrent users at remote sites of care. RESULTS: A stand-alone, pilot system is
      in operation at the BHCHP medical respite unit. Information on 129 patient
      encounters from 37 unique sites has been entered. A full client-server system has
      been designed. Benchmarks show that while the relative performance of a
      communication link based upon a phone line is 0.07 to 0.15 that of a local area
      network, optimization permits adequate response. CONCLUSION: Medical records
      access in a transient population poses special problems. Use of client-server and
      distributed database strategies can provide a technical foundation that provides
      a secure, reliable, and accessible computer-based medical record in this
      environment.

PMID- 7719801
TI  - On the relevance of discipline to informatics.

PMID- 7719802
TI  - Presentation of the Morris F. Collen, M.D. Medal to Dr. Morris F. Collen.

PMID- 7719803
TI  - The origins of informatics.
AB  - This article summarizes the origins of informatics, which is based on the
      science, engineering, and technology of computer hardware, software, and
      communications. In just four decades, from the 1950s to the 1990s, computer
      technology has progressed from slow, first-generation vacuum tubes, through the
      invention of the transistor and its incorporation into microprocessor chips, and
      ultimately, to fast, fourth-generation very-large-scale-integrated silicon chips.
      Programming has undergone a parallel transformation, from cumbersome, first
      generation, machine languages to efficient, fourth-generation application
      oriented languages. Communication has evolved from simple copper wires to complex
      fiberoptic cables in computer-linked networks. The digital computer has profound
      implications for the development and practice of clinical medicine.

PMID- 7719804
TI  - Toward a medical-concept representation language. The Canon Group.
AB  - The Canon Group is an informal organization of medical informatics researchers
      who are working on the problem of developing a "deeper" representation formalism
      for use in exchanging data and developing applications. Individuals in the group
      represent experts in such areas as knowledge representation and computational
      linguistics, as well as in a variety of medical subdisciplines. All share the
      view that current mechanisms for the characterization of medical phenomena are
      either inadequate (limited or rigid) or idiosyncratic (useful for a specific
      application but incapable of being generalized or extended). The Group proposes
      to focus on the design of a general schema for medical-language representation
      including the specification of the resources and associated procedures required
      to map language (including standard terminologies) into representations that make
      all implicit relations "visible," reveal "hidden attributes," and generally
      resolve ambiguous or vague references. The Group is proceeding by examining large
      numbers of texts (records) in medical sub-domains to identify candidate
      "concepts" and by attempting to develop general rules and representations for
      elements such as attributes and values so that all concepts may be expressed
      uniformly.

PMID- 7719805
TI  - A logical foundation for representation of clinical data.
AB  - OBJECTIVE: A general framework for representation of clinical data that provides
      a declarative semantics of terms and that allows developers to define explicitly
      the relationships among both terms and combinations of terms. DESIGN: Use of
      conceptual graphs as a standard representation of logic and of an existing
      standardized vocabulary, the Systematized Nomenclature of Medicine (SNOMED
      International), for lexical elements. Concepts such as time, anatomy, and
      uncertainty must be modeled explicitly in a way that allows relation of these
      foundational concepts to surface-level clinical descriptions in a uniform manner.
      RESULTS: The proposed framework was used to model a simple radiology report,
      which included temporal references. CONCLUSION: Formal logic provides a framework
      for formalizing the representation of medical concepts. Actual implementations
      will be required to evaluate the practicality of this approach.

PMID- 7719806
TI  - A schema for representing medical language applied to clinical radiology.
AB  - OBJECTIVE: Develop a representational schema for clinical concepts and apply it
      to the task of encoding radiology reports of the chest. DESIGN: The schema was
      developed following a manual analysis of sample reports from the domain. The
      schema has two main components: the Medical Entities Dictionary (MED), which
      specifies the formal representation of the concepts in the domain and of their
      structures, and the natural-language processor, which specifies the linguistic
      expressions of the concepts. The schema was evaluated by applying it to a test
      set of 7,500 reports. Two-hundred reports from the test set were manually
      analyzed by a medical expert to determine the accuracy and success rate of the
      system. RESULTS: 82% of the 7,500 reports that contained relevant clinical
      information were successfully structured automatically. For the smaller set of
      200 reports, 80% were structured successfully with an accuracy rate of 97%.
      CONCLUSIONS: The schema is a formal representation for clinical concepts in
      radiology reports, and provides domain coverage that is particularly well-suited
      for natural-language processing of radiology for use in a decision support
      system.

PMID- 7719807
TI  - Experiments in concept modeling for radiographic image reports.
AB  - OBJECTIVE: Development of methods for building concept models to support
      structured data entry and image retrieval in chest radiography. DESIGN: An
      organizing model for chest-radiographic reporting was built by analyzing manually
      a set of natural-language chest-radiograph reports. During model building,
      clinician-informaticians judged alternative conceptual structures according to
      four criteria: content of clinically relevant detail, provision for semantic
      constraints, provision for canonical forms, and simplicity. The organizing model
      was applied in representing three sample reports in their entirety. To explore
      the potential for automatic model discovery, the representation of one sample
      report was compared with the noun phrases derived from the same report by the
      CLARIT natural-language processing system. RESULTS: The organizing model for
      chest-radiographic reporting consists of 62 concept types and 17 relations,
      arranged in an inheritance network. The broadest types in the model include
      finding, anatomic locus, procedure, attribute, and status. Diagnoses are modeled
      as a subtype of finding. Representing three sample reports in their entirety
      added 79 narrower concept types. Some CLARIT noun phrases suggested valid
      associations among subtypes of finding, status, and anatomic locus. CONCLUSIONS:
      A manual modeling process utilizing explicitly stated criteria for making
      modeling decisions produced an organizing model that showed consistency in early
      testing. A combination of top-down and bottom-up modeling was required. Natural
      language processing may inform model building, but algorithms that would replace
      manual modeling were not discovered. Further progress in modeling will require
      methods for objective model evaluation and tools for formalizing the model
      building process.

PMID- 7719808
TI  - Strategic planning activities of the American Medical Informatics Association.
AB  - The American Medical Informatics Association (AMIA) has begun the process of long
      range strategic plan development. The AMIA Board of Directors established an Ad
      Hoc Strategic Planning Task Force, with the goal of initiating such planning in
      November 1992. In January 1993, the Task Force convened a group of AMIA members
      in order to develop an initial set of goals and objectives. The group consisted
      of past and present AMIA Board members, AMIA Committee chairpersons,
      representative AMIA Working Group chairpersons, the AMIA Executive Director and
      members of the AMIA office staff, and a number of AMIA members-at-large. The
      group created a draft strategic plan, which was refined by the Task Force after
      circulation among two focus groups and through a mailing to the AMIA membership.
      This report of the AMIA strategic planning process is intended to create a
      historical record and to stimulate further discussion of a working plan that will
      evolve over time. AMIA will continue the strategic planning process through its
      Ad Hoc Strategic Planning Committee as it begins to implement aspects of the
      strategic plan over the next several years.

PMID- 7719809
TI  - An evaluation of factors influencing Bayesian learning systems.
AB  - OBJECTIVES: To examine the influences of situational and model factors on the
      accuracy of Bayesian learning systems. DESIGN: This study examines the impacts of
      variations in two situational factors, training sample size and number of
      attributes, and in two model factors, choice of Bayesian model and criteria for
      excluding model attributes, on the overall accuracy of Bayesian learning systems.
      MEASUREMENTS: The test data were derived from myocardial infarction patients who
      were admitted to eight hospitals in New Orleans during 1985. The test sample
      consisted of 339 cases; the training samples included 100, 400, and 800 cases.
      APACHE II variables were used for the model attributes and patient discharge
      status as the outcome predicted. Attribute sets were selected in sizes of 4, 8,
      and 12. The authors varied the Bayesian models (proper and simple) and the
      attribute exclusion criteria (optimism and pessimism). RESULTS: The simple Bayes
      model, which assumes conditional independence, consistently equalled or
      outperformed the proper (maximally dependent) Bayes model, which assumes
      conditional dependence, across all training sample and attribute set sizes. Not
      excluding model attributes was found to be preferable to using sample theory as
      an attribute exclusion criterion in both the simple and the proper models.
      CONCLUSION: In the domain tested, the simple Bayes model with optimistic
      exclusion is more robust than previously assumed and increasing the number of
      attributes in a model had a greater relative impact on model accuracy than did
      increasing the number of training sample cases. Assessment of applicability of
      these findings to other domains will require further study. In addition, other
      models that are between these two extremes must be investigated. These include
      models that approximate proper Bayes' conditional dependence computations while
      requiring fewer training sample cases, attribute exclusion criteria between
      optimism and pessimism that improve accuracy, and ordering techniques for
      introducing attributes into Bayes models that optimize the information value
      associated with the attributes in test-sample cases.

PMID- 7719811
TI  - Controlled medical vocabulary construction: methods from the Canon Group.

PMID- 7719810
TI  - Performances of 27 MEDLINE systems tested by searches with clinical questions.
AB  - OBJECTIVE: To compare the performances of online and compact-disc (CD-ROM)
      versions of the National Library of Medicine's (NLM) MEDLINE database. DESIGN:
      Analytic survey. INTERVENTION: Clinical questions were drawn from 18 searches
      originally conducted spontaneously by clinicians from wards and clinics who had
      used Grateful Med Version 4.0. Clinicians' search strategies were translated to
      meet the specific requirements of 13 online and 14 CD-ROM MEDLINE systems. A
      senior librarian and vendors' representatives constructed independent searches
      from the clinicians' questions. The librarian and clinician searches were run
      through each system, in command mode for the librarian and menu mode for
      clinicians, when available. Vendor searches were run through the vendors' own
      systems only. MAIN MEASUREMENTS: Numbers of relevant and irrelevant citations
      retrieved, cost (for online systems only), and time. RESULTS: Systems varied
      substantially for all searches, and for librarian and clinician searches
      separately, with respect to the numbers of relevant and irrelevant citations
      retrieved (p < 0.001 for both) and the cost per relevant citation (p = 0.012),
      but not with respect to the time per search. Based on combined rankings for the
      highest number of relevant and the lowest number of irrelevant citations
      retrieved, the SilverPlatter CD-ROM MEDLINE clinical journal subset performed
      best for librarian searches, while the PaperChase online system worked best for
      clinician searches. For cost per relevant citation retrieved, Dialog's Knowledge
      Index performed best for both librarian and clinician searches. CONCLUSIONS:
      There were substantial differences in the performances of competing MEDLINE
      systems, and performance was affected by search strategy, which was conceived by
      a librarian or by clinicians.

PMID- 7719812
TI  - The position of the Canon Group: a reality check.

PMID- 7719813
TI  - CDC WONDER: a cooperative processing architecture for public health.
AB  - CDC WONDER is an information management architecture designed for public health.
      It provides access to information and communications without the user's needing
      to know the location of data or communication pathways and mechanisms. CDC WONDER
      users have access to extractions from some 40 databases; electronic mail (e
      mail); and surveillance data processing. System components include the Remote
      Client, the Communications Server, the Queue Managers, and Data Servers and
      Process Servers. The Remote Client software resides in the user's machine; other
      components are at the Centers for Disease Control and Prevention (CDC). The
      Remote Client, the Communications Server, and the Applications Server provide
      access to the information and functions in the Data Servers and Process Servers.
      The system architecture is based on cooperative processing, and components are
      coupled via pure message passing, using several protocols. This architecture
      allows flexibility in the choice of hardware and software. One system limitation
      is that final results from some subsystems are obtained slowly. Although designed
      for public health, CDC WONDER could be useful for other disciplines that need
      flexible, integrated information exchange.

PMID- 7719814
TI  - Security versus access: trade-offs are only part of the story.

PMID- 7719815
TI  - Against simple universal health-care identifiers.

PMID- 7719816
TI  - Integrated computerized records provide improved quality of care with little loss
      of privacy.

PMID- 7719817
TI  - Privacy and medical record information.

PMID- 7719818
TI  - Use of administrative records to describe longitudinal patterns of health
      services use among veterans.
AB  - Administrative records of the Department of Veterans Affairs (DVA) and the
      National Death Index were linked to create a four-year longitudinal database that
      describes the clinical status, hospital and nursing home use, and mortality for a
      nationwide cohort of persons admitted to DVA nursing homes (n = 23,039). Using
      Social Security Numbers as identifiers, the records of only 6% of these persons
      had logically inconsistent or implausible patterns. Nineteen percent of the
      remaining records had correctable logical errors. Information on the creation,
      consistency, and potential uses of this database may prove useful to health
      services researchers interested in describing longitudinal patterns of health
      care use across multiple settings within and outside the DVA.

PMID- 7719819
TI  - Information retrieved from a database and the augmentation of personal knowledge.
AB  - OBJECTIVE: To assess the degree to which information retrieved from a biomedical
      database can augment personal knowledge in addressing novel problems, and how the
      ability to retrieve information evolves over time. DESIGN: This longitudinal
      study comprised three assessments of two cohorts of medical students. The first
      assessment occurred just before student course experience in bacteriology, the
      second occurred just after the course, and the third occurred five months later.
      At each assessment, the students were initially given a set of bacteriology
      problems to solve using their personal knowledge only. Each student was then
      reassigned a sample of problems he or she had answered incorrectly, to work again
      with assistance from a database containing information about bacteria and
      bacteriologic concepts. The initial pass through the problems generated a
      "personal knowledge" score; the second pass generated a "database-assisted" score
      for each student at each assessment. RESULTS: Over two cohorts, students'
      personal knowledge scores were very low (approximately 12%) at the first
      assessment. They rose substantially at the second assessment (approximately 48%)
      but decreased six months later (approximately 25%). By contrast, database
      assisted scores rose linearly: from approximately 44% at the first assessment to
      approximately 57% at the second assessment, to approximately 75% at the third
      assessment. CONCLUSION: The persistent increase in database-assisted scores, even
      when personal knowledge had attenuated, was the most remarkable finding of this
      study. While some of the increase may be attributed to artifacts of the design,
      the pattern seems to result from the retained ability to recognize problem
      relevant information in a database even when it cannot be recalled.

PMID- 7719820
TI  - Computerized decision support for concurrent utilization review using the HELP
      system.
AB  - OBJECTIVE: Development and evaluation of computerized concurrent utilization
      review (UR) support taking advantage of a clinically rich computerized patient
      database. DESIGN: The Automated Support System for Utilization Review (ASSURE)
      applies the Appropriateness Evaluation Protocol (AEP) Day of Care criteria to
      computerized patient data in the HELP hospital information system. This paper
      reports the development, verification, and validation of ASSURE. MEASUREMENTS:
      Implementation correctness was verified by measuring agreement with a nurse
      reviewer, using separate sample sets for all 20 criteria for a total of 560
      current inpatients. Usefulness in detecting inappropriate days of care was
      validated by two nurse reviewers who were crossed with manual and computer
      assisted review methods in a blocked design for 168 current inpatients. Agreement
      with reviewers, sensitivity, specificity, positive predictive value, and negative
      predictive value were measured. RESULTS: Agreement was very good for satisfaction
      of criteria, and good for appropriateness of day of care. A patient day
      identified by ASSURE as potentially inappropriate would be twice as likely to be
      judged inappropriate by a reviewer as a randomly selected patient day. Review of
      the 10% of patient days identified as potentially inappropriate by ASSURE would
      identify approximately 21% of the inappropriate days of care. CONCLUSION: ASSURE
      is a clinically useful tool for screening adult acute care patients for
      inappropriate days of care, and promises to make a major contribution to reducing
      health care costs. The prognosis for successful routine clinical use is good.

PMID- 7719821
TI  - A plea for controlled trials in medical informatics.

PMID- 7719822
TI  - Acetabulum pedis. Part I: Talocalcaneonavicular joint socket in normal foot.
AB  - The socket of the talocalcaneonavicular ball and socket joint in the foot is
      termed acetabulum pedis (AP). Observations of 72 feet from necropsies of
      stillborns or deceased newborns are the basis of our architectural description of
      AP. It has five walls: the roof or superior wall, the floor or inferior wall, the
      bottom or anterior wall, the medial wall, and the lateral wall. Variations in the
      tridimensional situation of the anterior and middle articular facets of the
      calcaneus modify the acetabular floor area. The same is true of the variations in
      position of the ligaments in both the acetabular floor and the medial wall. These
      modifications of the acetabular floor and medial wall areas can change the shape
      of the foot.

PMID- 7719823
TI  - Physiologic bowing in children: an analysis of the pendulum mechanism.
AB  - Prompted by common observations, we investigated why physiologic bowing occurs in
      infants and what purpose is served by its characteristic varus to valgus to
      neutral movement of the mechanical axis of the knee which we term "pendulum-like
      swing" in the frontal plane. Anthropomorphic data were readily available on age
      related increase in weight, femoral and tibial lengths, and changes in lower
      extremity to allow construction of an "average" leg representing "normal" limb
      alignment of a growing infant male aged 1-8 years. This enabled us to calculate
      the bending moments on five anatomic levels of the limb about the knee; more
      important, during some growth periods the bending moments are minimal and may be
      used to diagnose pathologies of the lower limb. This form of analysis may prove
      useful in pathologies in which mechanisms serve to "mask" problems diagnosed on
      the basis of knee angle alone. When the child begins to stand, the pendulum
      mechanism is needed to equalize physeal growth about the knee.

PMID- 7719824
TI  - Hunter's syndrome as a cause of childhood carpal tunnel syndrome: a report of
      three cases.
AB  - Carpal tunnel syndrome is common in adults but rare in children. It is known to
      occur in association with the mucopolysaccharidoses and other systemic conditions
      in childhood. We describe three children with a mild variant of
      mucopolysaccharidosis II (Hunter's syndrome) in whom disabling median nerve
      compression was treated by standard decompression.

PMID- 7719825
TI  - Acetabulum pedis. Part II: Talocalcaneonavicular joint socket in clubfoot.
AB  - Many pathoanatomic studies of clubfeet have been made. Bone changes and ligament
      and tendon alterations are among the different deformities reported in the
      literature. The socket of the talocalcaneonavicular joint is termed the
      acetabulum pedis (AP), and alterations of the joint have been reported previously
      as malformations associated with clubfoot. We report pathoanatomic observations
      of AP in three human clubfoot specimens. Anomalies in AP were observed and
      compared with those in normal feet. In such cases, AP volume is restricted.
      Surface area is reduced on the acetabular floor and medial wall. Changes occur in
      the osseous components as well as in the ligaments of the AP.

PMID- 7719826
TI  - Femoral head avascular necrosis associated with metaphyseal aneurysmal bone cyst.
AB  - A 12-year-old girl had an aneurysmal bone cyst in the proximal femoral metaphysis
      simultaneously with an avascular necrosis of the femoral head, as seen on
      radiological examination. No extension of the lesion across the growth plate into
      the femoral epiphysis was observed. The expansive behavior of this lesion (ABC)
      could have compromised the posterosuperior vascular supply of the femoral
      epiphysis, since no radiographic signs of fractures could be found. Vascular
      anomalies within the lesion that increase venous pressure could be another factor
      responsible for the decrease in the blood supply of the femoral epiphysis and
      could cause necrosis, hence compromising the morphology of the hip joint at
      maturity.

PMID- 7719827
TI  - A false aneurysm complicating a subcutaneous Achilles tendon lengthening.
AB  - Subcutaneous lengthening of the Achilles tendon is a routinely used technique in
      our department. We report a case with a severe complication after this minor
      procedure in a 13-year-old patient with cerebral palsy. Six weeks after the
      operation the patient had a false aneurysm caused by a lesion of the posterior
      tibial artery at the time of surgery. After ligating the artery and draining the
      false aneurysm, recovery was uneventful. Although subcutaneous lengthening is an
      easy and reliable operation, one has to keep in mind its possible complications.

PMID- 7719828
TI  - Growth arrest of the distal radial epiphysis in a javelin thrower: reversed
      Madelung?

PMID- 7719829
TI  - Bilateral compression of the median nerve by supracondylar spurs.

PMID- 7719830
TI  - Update on pathologic anatomy of clubfoot.
AB  - Serial histological sections in three planes (frontal, sagittal, and transverse)
      in four cases of clubfoot in fetuses aborted at 16-20 weeks were studied and
      compared to identical sections obtained in three normal feet. The talus was
      deformed, with its neck medially angulated and its head dome shaped. The body of
      the calcaneus was medially bowed and was tilted and rotated medially underneath
      the talus, and both the talus and the calcaneum were in plantar flexion. The
      tilting of the talus and the medial tilting and rotation of the calcaneus
      accounted for the varus deformity of the hindfoot. The varus and adduction
      deformity of the heel and midfoot caused the supination seen in clubfoot. The
      skeletal components of the forefoot were adducted as a result of the medial
      displacement of the navicular and cuboid. Ligamentous and tendon abnormalities
      were also observed with increased fibrosis of muscle tissue, which may be an
      important factor in causation of clubfoot.

PMID- 7719831
TI  - Calcaneocuboid joint deformity in talipes equinovarus: an overview and update.
AB  - The calcaneocuboid joint is significantly malaligned in some clubfeet.
      Calcaneocuboid deformity appears to be a combination of medial angulation of the
      calcaneocuboid joint with medial subluxation of the cuboid on the calcaneus. In
      moderate and severe cases, incomplete treatment of this deformity may result in
      rotary valgus of the hindfoot. One hundred consecutive cases of clubfeet
      requiring operative intervention, all treated at the Medical College of Wisconsin
      at Milwaukee between 1984 and 1988 were reviewed for incidence and treatment of
      calcaneocuboid abnormalities. A radiographic system of evaluation was devised,
      encompassing a normal grade of 0 and three grades of deformity based on the
      extent to which the midpoint of the cuboid had deviated from the longitudinal
      axis of the calcaneus or beyond the tangent defined by the edge of the calcaneus.
      The author's preferred surgical technique is described. Grade 1 deformity does
      not require operation; grade 2 deformity required extensive soft tissue release,
      and grade 3 deformity required a bone procedure in addition to extensive soft
      tissue release. The results demonstrated that partial release of the
      calcaneocuboid cuboid joint is never indicated because it may produce valgus of
      the hindfoot. Based on this sample, approximately 25% of all patients requiring
      operation will require calcaneocuboid release. Operation should be performed
      without placing undue pressure on the joints, which may produce late fusion;
      plantar release may be indicated as a means of reducing pressure on the joint
      surfaces. Operation before ossification of the cuboid should be avoided.

PMID- 7719832
TI  - Assessment of calcaneocuboid joint deformity by magnetic resonance imaging in
      talipes equinovarus.

PMID- 7719833
TI  - Three-dimensional analysis of clubfoot deformity by computed tomography.
AB  - The bony pathoanatomy of clubfoot has been assessed by a three dimensional
      reconstruction of transverse CT images obtained from 27 feet in children aged 3
      10 years. Principal axes of the bones were determined to quantitate interosseous
      deformity, while visual inspection of the reconstructed images demonstrated
      intraosseous deformity. "Medial spin" and midfoot adduction were analyzed on the
      AP view of the foot ("top" view), while hindfoot pronosupination was analyzed on
      the AP view of the ankle (posterior view). This technique allows visualization of
      deformities which normally cannot be analyzed on plain radiographs, and also
      shows that a variety of interosseous relationships make up the clinical entity
      known as clubfoot. Abnormal talar pronation ("intorsion") was an unexpected
      finding of this three dimensional analysis.

PMID- 7719834
TI  - Evaluation of residual clubfoot deformities using gait analysis.
AB  - Gait analysis was used to evaluate 15 patients who had previously undergone
      clubfoot surgery. Because six patients had had bilateral surgery, 21 feet had
      undergone previous clubfoot surgery. Three of the operated feet had no residual
      deformity. In the remaining 18 feet, the reason for referral was intoeing in 13,
      calcaneovalgus in three, hindfoot varus in one, and supination/adduction in one.
      Clinical assessment and information from the gait analysis were used to establish
      a treatment plan. Satisfactory treatment outcome was achieved in 13 patients, one
      result was unsatisfactory, and one result was undetermined.

PMID- 7719835
TI  - Intraoperative ultrasound for evaluation of reduction in congenital talipes
      equinovarus.
AB  - A technique of intraoperative ultrasound for evaluation of reduction in
      congenital talipes equinovarus (CTEV) is reported. Ultrasound (US) scanning
      enables the surgeon to perform controlled reduction of both calcaneocuboid and
      talonavicular joint during the operation because visualization of the relation in
      the medial and lateral column of the foot is as precise as that obtained with
      radiographs. The relation between talus and calcaneus in the horizontal plane
      cannot be visualized. Examination is quick and simple but is more easily
      performed if the shape of the foot is near-normal; i.e., the foot has been well
      prepared for operation by nonoperative treatment.

PMID- 7719836
TI  - Staged lengthening in the prevention of dwarfism in achondroplastic children: a
      preliminary report.
AB  - We present our experience, since 1983, in lower-limb lengthening for the
      treatment of achondroplasic dwarfism. We stress the importance of our method,
      staged lengthening, which includes two separate operations on the tibia, at the
      ages of 5 and 10, and two on the femurs, at the ages of 6 and 12. This method
      allows an overall increase in height varying from 30 to 35 cm and has the
      advantage of minimizing complications, since children tolerate the lengthening
      related problems far better. In 9 years 28 children have undergone limb
      lengthening, and six of these patients have now completed the first three stages,
      obtaining a total increase in length from 18 to 23 cm. We discuss the staged
      lengthening program, pointing out advantages and disadvantages of the method.

PMID- 7719837
TI  - Ultrasound: a helpful guide in the treatment of congenital talipes equinovarus.
AB  - Ultrasound may be used to distinguish the unossified cartilage and the
      ossification centres of the tarsal bones. The use of ultrasound to image the
      normal foot and the foot with congenital talipes equinovarus (CTEV) deformity has
      been assessed. We describe two standard ultrasound planes that enable the normal
      foot to be distinguished from the foot with a CTEV deformity even before it
      becomes clinically apparent. The technique does not take much time, is easily
      tolerated by the child, and may be repeated frequently to assess the response to
      treatment. It can be learned easily.

PMID- 7719838
TI  - Foot deformity and the length of the triceps surae in Danish children between 3
      and 17 years old.
AB  - We report the results of examination in 1991 of 759 children and adolescents
      between 3 and 17 years old, comprising 98% of pupils in different age groups from
      seven schools and ten kindergartens in Funen (Denmark). The triceps surae was
      considered to be short if the foot held with the talus in neutral position
      relative to the calcaneus could only be dorsiflexed to a right angle. The
      proportion of children with shortening of one or both triceps surae rose from 24%
      to 62% between the ages of 3 and 17 years with no difference between the sexes.
      In 13% of adolescents, one or both feet failed to reach a right angle by > or = 5
      degrees. Footprints made in 1,520 feet showed that the proportion of feet with a
      high arch increased from 2% to 7%; there was a smaller number of such feet with a
      short triceps surae than in feet with a normal arch. The proportion of feet with
      a flat arch declined from 42% to 6% in spite of a strong relationship with a
      short triceps surae. In the oldest age group, all the flat feet had a short
      triceps surae, which is probably one of the reasons for the persistence of the
      deformity.

PMID- 7719839
TI  - Remodeling of the calcaneus apophysis in the growing child.
AB  - Radiography and computer-aided analysis of tomography of the os calcis in 35
      children with Sever's disease and of 52 control children were concurrently
      evaluated with histologic appearance of six calcanei of victims of road
      accidents, which were radiographically compatible with the same syndrome.
      Histology showed abrupt interruption in continuity of the apophysis of
      perpendicular fibrous plates with evidence of an ongoing reparative process.
      Computer-aided analysis of orientation of the "fragmentation" lines and
      histologic data both support the hypothesis of a stress remodeling process owing
      to excessive bending forces acting on the calcaneal apophysis.

PMID- 7719840
TI  - The ground reaction force in the gait of intoeing children.
AB  - One hundred twenty-four intoeing and 80 age-matched normal children were studied
      using the Kistler force plate. Intoeing gait was usually caused by increased
      femoral anteversion (IFA), internal tibial torsion (ITT), or metatarsus adductus
      (MAD). Thirty-five children showing spontaneous correction and a return to normal
      gait (COR) were singled out. Our results confirmed that there were variations of
      the ground reaction force (GRF) in three directions in the different groups,
      particularly in the vertical and medial-lateral components. Alterations of
      magnitude of GRF or duration of stance phase was found to be significant compared
      with normal subjects. On this basis, we suggest that dynamic forces are related
      to the remodeling of the epiphyseal plate or respond to actions of the plantar
      flexors, although we could not discern a specific correlation between them.

PMID- 7719841
TI  - Selection of fusion levels in idiopathic adolescent scoliosis treated by
      Harrington-DDT instrumentation: a short-term radiologic study.
AB  - Clinical records and radiographs of 106 patients treated by Harrington-dorsal
      transverse traction (DDT) instrumentation for idiopathic adolescent thoracolumbar
      scoliosis were reviewed. Our strategy was to fuse from one vertebra above the
      measured curve to two vertebrae below the curve, but to avoid fusions below the
      third lumbar vertebra. With this strategy, the lower level of fusion rarely
      coincided with the stable vertebra. In King type 2 and type 3 scolioses, the best
      results were obtained when the lower fusion level coincided with the stable
      vertebra. In King type 4 and in most King type 5 scolioses, the lower level of
      fusion was two or three vertebrae short of the stable vertebra; nevertheless, we
      obtained good corrections. We conclude that in King type 4 and type 5 scolioses
      extensive lumbar fusion can be avoided.

PMID- 7719842
TI  - Altered skeletal growth in Perthes' disease: an anthropometric study of children
      from rural India.
AB  - In contrast to the features of Perthes' disease (PD) in England, children with PD
      in South west India are older and from rural areas. To test whether rural Indian
      children with PD demonstrate abnormalities in skeletal growth similar to those
      noted in English children, we studied 52 affected children and 100 normal
      controls. Each child had a detailed anthropometric evaluation; various body
      segments were measured. The study demonstrated that rural Indian children with PD
      showed impaired skeletal growth, with the feet most severely affected. The
      pattern of growth alteration was almost identical to that of English children
      with PD. The results suggest that despite difference in age of onset and rural
      urban differences in Indian and English children with PD, a common etiologic
      factor responsible for skeletal retardation is active in both groups.

PMID- 7719843
TI  - Imaging strategies in the first 12 months after reduction of developmental
      dislocation of the hip.
AB  - We have reviewed the records of 32 infants whose developmental dislocation of the
      hip (DDH) was treated by reduction and immobilization in a plaster cast. We
      examined 50 CT scans from 22 patients. The postreduction radiological studies led
      to a change of cast in 10 patients and, in five of them, the subluxation shown on
      CT scan was not seen in an earlier radiograph. Where reduction has been
      undertaken at the time of arthrography or in an older child, a plain radiograph
      may be adequate to confirm the position in the cast. In an infant, CT scans give
      superior information, have acceptable risks, and should be used in association
      with radiation protection measures.

PMID- 7719844
TI  - A familiar ring.

PMID- 7719845
TI  - What is the molten globule?

PMID- 7719846
TI  - Oligomer evolution in action?

PMID- 7719847
TI  - Electron cryomicroscopy and angular reconstitution used to visualize the skeletal
      muscle calcium release channel.
AB  - We exploit the random orientations of ice-embedded molecules imaged in an
      electron cryomicroscope to determine the three-dimensional structure of the
      Ca(2+)-release channel from the sarcoplasmic reticulum (SR) in its closed state,
      without tilting the specimen holder. Our new reconstruction approach includes an
      exhaustive search of all different characteristic projection images in the
      micrographs and the assignment of Euler angle orientations to these views. The 30
      A map implied reveals a structure in which the transmembrane region exhibits no
      apparent opening on the SR lumen side. The extended cytoplasmic region has a
      hollow appearance and consists, in each monomer, of a clamp-shaped and a handle
      shaped domain.

PMID- 7719848
TI  - A ribosomal protein module in EF-G and DNA gyrase.
AB  - A novel common fold observed in the structures of elongation factor G, DNA gyrase
      B, and ribosomal protein S5 displays a rare topological feature suggesting the
      high probability of an evolutionary relationship.

PMID- 7719849
TI  - Picture story. Heads you bind, tails you bind.SH3 domains.

PMID- 7719850
TI  - Defining protein interactions with yeast actin in vivo.
AB  - Using the two-hybrid protein interaction reporter system, actin, profilin, Srv2p
      and two SH3-containing proteins are found to bind yeast actin in vivo. When
      tested for ability to interact with 35 actin mutations distributed over the
      monomer surface, distinct subsets of mutations characteristic for each putative
      ligand are found to disrupt binding. In particular, the pattern of differential
      interactions for the actin-actin interaction is consistent with published
      structures for the actin filament. Despite functional similarities, the patterns
      of differential interaction for Srv2p and profilin are different. In contrast,
      the patterns for profilin and the SH3 domain proteins suggest a shared binding
      site and commonality in mechanism.

PMID- 7719851
TI  - How do the GTPases really work?

PMID- 7719852
TI  - Substrate-assisted catalysis as a mechanism for GTP hydrolysis of p21ras and
      other GTP-binding proteins.
AB  - Despite many advances in understanding the structure and function of GTP-binding
      proteins the mechanism by which these molecules switch from the GTP-bound on
      state to the GDP-bound off-state is still poorly understood. Theoretical studies
      suggest that the activation of the nucleophilic water which hydrolyzes GTP needs
      a general base. Such a base could not be located in any of the many GTP-binding
      proteins. Here we present a unique type of linear free energy relationships that
      not only supports a mechanism for p21ras in which the substrate GTP itself acts
      as the catalytic base driving the GTPase reaction but can also help to explain
      why certain mutants of p21ras are oncogenic and others are not.

PMID- 7719853
TI  - Ionic interactions and the global conformations of the hammerhead ribozyme.
AB  - Here we investigate the global conformation of the hammerhead ribozyme.
      Electrophoretic studies demonstrate that the structure is folded in response to
      the concentration and type of ions present. Folding based on colinear alignment
      of arms II and III is suggested, with a variable angle subtended by the remaining
      helix I. In the probable active conformation, a small angle is subtended between
      helices I and II. Using uranyl photocleavage, an ion binding site has been
      detected in the long single-stranded region. The folded conformation could
      generate a preactivation of the scissile bond to permit in-line attack of the 2'
      hydroxyl group, with a bound metal ion playing an integral role in the chemistry.

PMID- 7719854
TI  - Structure of an RNA double helix including uracil-uracil base pairs in an
      internal loop.
AB  - The crystal structure of the RNA dodecamer 5'-GGACUUUGGUCC-3' has been determined
      from X-ray diffraction data to 2.6 A resolution. This oligomer forms an
      asymmetric double helix in the crystal. Four consecutive non-Watson-Crick base
      pairs are formed in the middle of the duplex including the first intrahelical U-U
      (or T-T) pairs observed in an oligonucleotide crystal structure. Two different
      conformations of U-U pairs are observed in the context of the surrounding
      sequence. One of these pairs is highly twisted, allowing a bound water to bridge
      across strands in the major groove. The crystal packing illustrates a new form of
      RNA helix-helix interaction.

PMID- 7719855
TI  - The lipoamide arm in the glycine decarboxylase complex is not freely swinging.
AB  - Glycine decarboxylase consists of four protein components. Its structural and
      mechanistic heart is provided by the lipoic acid-containing H-protein which
      undergoes a cycle of reductive methylamination, methylamine transfer and electron
      transfer. Lipoic acid attached to a specific lysine side chain is assumed to act
      as a 'swinging arm' conveying the reactive dithiolane ring from one catalytic
      centre to another. The X-ray crystal structures of two forms of the H-protein
      have been determined. The lipoate cofactor is located in the loop of a hairpin
      configuration but following methylamine transfer it is pivoted to bind into a
      cleft at the surface of the H-protein. The lipoamide-methylamine arm is,
      therefore, not free to move in aqueous solvent.

PMID- 7719857
TI  - Minor groove DNA-recognition by alpha-helices.

PMID- 7719856
TI  - The allosteric ligand site in the Vmax-type cooperative enzyme phosphoglycerate
      dehydrogenase.
AB  - The crystal structure of the phosphoglycerate dehydrogenase from Escherichia coli
      is unique among dehydrogenases. It consists of three clearly separate domains
      connected by flexible hinges. The tetramer has approximate 222 symmetry with the
      principal contacts between the subunits forming between either the nucleotide
      binding domains or the regulatory domains. Two slightly different subunit
      conformations are present which vary only in the orientations of the domains.
      There is a hinge-like arrangement near the active site cleft and the serine
      effector site is provided by the regulatory domain of each of two subunits.
      Interdomain flexibility may play a key role in both catalysis and allosteric
      inhibition.

PMID- 7719858
TI  - Neutron diffraction analysis of the solvent accessible volume in cubic insulin
      crystals.
AB  - The average contact distance between protein and solvent surface atoms in cubic
      insulin crystals has been determined from two sets of 15 A resolution neutron
      diffraction data. A contact distance between the water hydrogen sites and the
      protein surface that is significantly shorter than the average protein-water
      oxygen contact distance implies that many water molecules are oriented with
      hydrogen atoms pointed towards the protein surface. The shape of the
      protein/solvent interface is consistent with the protein envelope obtained from
      atomic co-ordinates.

PMID- 7719859
TI  - True knot of the umbilical cord: a difficult prenatal ultrasonographic diagnosis.
AB  - We examined retrospectively the use of ultrasonography in 18 cases in which a
      true knot of the umbilical cord was found at delivery. All women had a normal
      second-trimester scan in which no cord abnormality was detected. Thirteen (72%)
      also had third-trimester color Doppler ultrasonography, at which time the cord
      anomaly was again missed. In one of these cases the diagnosis could have been
      made with color flow imaging, but the abnormal pattern was mistaken instead for
      multiple loops of cord. On the other hand, the diagnosis of true knot was
      considered prenatally in two cases, but not confirmed at delivery, when only a
      prominent false knot was found in one and a normal cord in the other. We conclude
      that true knots of the umbilical cord do not have a characteristic appearance in
      utero and therefore are easily missed at routine prenatal ultrasonography.

PMID- 7719860
TI  - Accuracy of ultrasonic detection of the uterus in normal newborn infants:
      implications for infants with ambiguous genitalia.
AB  - Every year approximately one in 5000 babies is born with ambiguous genitalia, a
      condition that requires immediate sex assignment if possible. We investigated
      whether transabdominal ultrasonography with the use of a linear array high
      resolution 7.5-MHz transducer would enhance the accuracy of detecting the uterus
      in the newborn. One hundred mothers who delivered normal, term infants (> 36
      weeks and > 2500 g) gave their informed consent for the investigation. Each
      infant was placed in an unmarked bassinet, external genitalia were covered, and
      ultrasound examinations were performed by the same examiner (R.S.) who was
      blinded to the sex of the infant. The neonatal uterus was identified in 47 of 50
      female infants (94% sensitivity) and the absence of a uterus was correctly
      predicted in 49 of 50 male infants (specificity 98%). The average length of the
      neonatal uteri 1 day after birth was 3.2 +/- 0.5 cm and the total volume was 3.5
      +/- 0.9 cm3. An endometrial strip could be identified in 98% of neonatal uteri.
      We conclude that the use of the high-resolution 7.5-MHz transducer available in
      commercial ultrasound equipment is an accurate method for the detection of the
      neonatal uterus. Infants born with ambiguous genitalia who have a uterus will
      almost always be assigned the female sex. Infants with ambiguous genitalia but
      without a uterus will have male pseudohermaphroditism.

PMID- 7719862
TI  - Interobserver variability of sonographically determined second-trimester nuchal
      skinfold thickness measurements.
AB  - Twenty physicians experienced in fetal sonographic evaluation obtained fetal
      nuchal skinfold thickness measurements in each of five pregnant women between 16
      and 18 weeks' gestation. A random effects analysis of variance model was used to
      explore the sources of variation in the set of measurements, to determine the
      interobserver variability of sonographically measured second-trimester nuchal
      skinfold thickness. It was possible to obtain 96 measurements. Four measurements
      (all in the same patient) were deemed unobtainable due to fetal position. All
      recorded measurements were between 1.7 and 4.5 mm. The means (and ranges) for the
      five patients were 2.7 (1.7-3.6), 2.9 (2.0-4.5), 2.7 (2.0-4.0), 3.3 (2.2-4.0),
      and 2.7 (1.8-4.0) mm. The standard deviation for interobserver variability,
      caused by the combined effect of physician and machine imprecision, was 0.56 mm
      and the overall coefficient of variation was 19.8%. Interpatient differences were
      statistically significant (p = 0.004). Interphysician differences were not (p =
      0.11). We conclude that experienced physician sonographers using high-resolution
      ultrasound equipment are able to obtain second-trimester nuchal skinfold
      thickness measurements within 1.1 mm of the estimated true value with 95%
      probability.

PMID- 7719861
TI  - Are babies of normal birth weight who fail to reach their growth potential as
      diagnosed by ultrasound at increased risk?
AB  - The objectives of this study were to identify, by means of two third-trimester
      scans, fetuses with ultrasound evidence of inadequate growth but who were born
      with birth weights above the 10th centile for gestational age; and to determine
      if these infants constitute a high-risk group by comparing the incidence of
      obstetric intervention, of intrapartum complications and of neonatal morbidity
      between this group and the group of infants who showed no ultrasound evidence of
      intrauterine growth restraint. A total of 285 women with singleton pregnancies
      who were referred for a third-trimester ultrasound examination were included in
      this prospective study. Fetal weight was estimated by ultrasound twice in the
      third trimester and at each examination was assigned a centile score. A fall of >
      20 centiles was taken as evidence of inadequate growth. The outcomes measured
      were the incidence of abnormal umbilical artery Doppler, induction of labor,
      meconiumstaining of the liquor, intrapartum fetal blood sampling, operative
      vaginal delivery, Cesarean section, Apgar score of < 7 at 5 min and admission to
      the neonatal intensive care unit. Seventy-five patients showed a drop of > 20
      centiles between the first and second scans. The incidence of admission to the
      neonatal intensive care unit was greater in those infants who had ultrasound
      evidence of growth restraint. We conclude that infants of normal birth weight
      with inadequate growth diagnosed on ultrasound are not at increased risk, they
      have an increased incidence of admission to the neonatal intensive care unit, and
      they are more commonly found in mothers with diabetes mellitus.

PMID- 7719863
TI  - Predicting head circumference at birth: a study in a Dutch population using the
      Rossavik growth model.
AB  - The use of the Rossavik growth model for predicting neonatal head circumference
      from data obtained from two ultrasound scans before 28 weeks' menstrual age was
      investigated in 50 pregnant women with singleton pregnancy in a Dutch population.
      The head circumference predicted at 38, 39, 39.5 and 40 weeks' gestation and at
      birth was compared to the head circumference observed at birth. The accuracy was
      expressed in percentage difference and the growth potential realization index
      (GPRIHC) was used as an indicator of growth outcome. The predictions at 39.5
      weeks and 40 weeks were accurate without systematic error. Prediction at 38 weeks
      showed a statistical underprediction (mean +/- SD = -2.3 +/- 2.0%, p < 0.05) and
      at birth a systematic overprediction (mean +/- SD = +1.4 +/- 2.1%, p < 0.05).
      Based on the regression analyses of percentage differences against birth ages,
      the growth of the head circumference appeared to stop at about 39.5 weeks. The
      results of the present study were compared to studies of populations in the
      United States. The growth of the head circumference before 28 weeks was similar
      in all samples studied, but growth cessation was at 38 weeks in the fetuses in
      the USA and at 39.5 weeks in these Dutch fetuses. The mean values of GPRIHC were
      not different from 100% in all samples studied and the ranges were similar (mean,
      100.3%; range, 97-103% in the present study).

PMID- 7719864
TI  - Endovaginal Doppler ultrasound in ovarian torsion: a case series.
AB  - Four women with acute pelvic pain clinically suspected to be secondary to ovarian
      torsion were examined with gray-scale and Doppler ultrasound. All affected
      ovaries were enlarged (volumes 3.2-34 times the volumes of the ovaries on the
      unaffected sides). Three ovaries showed no internal flow, and one showed internal
      arterial flow. Ovary-conserving treatment was attempted in all four cases but the
      three ovaries which showed no evidence of internal flow eventually required
      removal. The fourth case, in which arterial flow was present on Doppler
      examination, was treated only with laparoscopic untwisting of the pedicle and did
      not require oophorectomy. The results of our study suggest that Doppler findings
      may distinguish ovaries which are beyond salvage and require removal from those
      which may be saved by prompt laparoscopic untwisting of the adnexa, but further
      studies with larger numbers of patients will be necessary.

PMID- 7719865
TI  - Localization of small ovarian Sertoli-Leydig cell tumors by transvaginal
      sonography with color Doppler.
AB  - Color Doppler ultrasound is a non-invasive diagnostic modality that has been
      gaining popularity in the evaluation of gynecological tumors. It demonstrates
      blood flow in a visually familiar way, and facilitates detection of
      neovascularity in pelvic tumors. In this article we describe, for the first time,
      a case in which a small androgen-producing ovarian tumor was localized by color
      Doppler ultrasound after other non-invasive imaging techniques failed.

PMID- 7719866
TI  - Trisomy 22: prenatal diagnosis--a case report.
AB  - Multiple abnormalities of a fetus were detected on a routine antenatal anomaly
      scan at 19 weeks' gestation. Amniocentesis and karyotype analysis showed trisomy
      22. The ultrasound and postmortem features are presented.

PMID- 7719867
TI  - Spontaneous remission of double pulsatile umbilical venous flow in twin-twin
      transfusion syndrome: a case report.
AB  - Double umbilical pulsatile venous flow is a rare event generally associated with
      fetal right heart failure. We observed, at 21 weeks' gestation, this venous flow
      pattern in a case of twin-twin transfusion syndrome occurring in the recipient
      twin affected by severe hydrops. In spite of a spontaneous remission of fetal
      hydrops at 30 weeks, the fetus died suddenly in utero, 2 weeks later. We
      hypothesized that this unexpected event was related to reversed acute twin-twin
      transfusion, and concluded that fetal hydrops remission in twin-twin transfusion
      syndrome must not be considered as a reassuring prognostic index but as an
      indication of the need for continuing biophysical monitoring.

PMID- 7719868
TI  - Reverse end-diastolic umbilical artery blood flow at 11 weeks' gestation.
AB  - This report describes a case of reverse end-diastolic blood flow in the umbilical
      artery of one of the fetuses of a twin pregnancy at 11 weeks' gestation.
      Cytogenetic studies after amniocentesis performed at 12 weeks revealed a 45.X
      karyotype of this twin whose death was registered 1 week later. Spontaneous
      delivery of the co-twin occurred at 37 weeks; the newborn was healthy and normal.
      This is the earliest record of reverse diastolic flow in the umbilical artery.
      Even in the first trimester of pregnancy this is an ominous sign and fatal demise
      is expected.

PMID- 7719869
TI  - The mentor.

PMID- 7719870
TI  - The single artery umbilical cord: it is worth screening for antenatally?

PMID- 7719871
TI  - Cephalocele detection in utero: sonographic and clinical features.
AB  - Sonographic and clinical features of 26 fetal cephaloceles were reviewed
      retrospectively. The most frequent reason for referral was elevated maternal
      serum alpha-fetoprotein levels. The smallest lesion identified was 0.4 x 0.5 cm
      (frontal, at 20 weeks); the largest was 9.0 x 10.0 cm (frontal, at 27 weeks).
      Twenty-four of 26 cephaloceles were detected on prenatal ultrasound examination;
      in 13 of these, more than 50% of the intracranial contents were exteriorized.
      Fifteen of 24 cephaloceles detected prenatally had a sulcal pattern (identified
      between 16 and 36 weeks' gestation); five were solid without a sulcal pattern
      (identified between 13 and 21 weeks' gestation), three were cystic, and one
      underwent a change in appearance from solid at 21 weeks to cystic at 26 weeks.
      Other cranial features were evaluated and included visible skull defect, seen in
      23/24 (96%), ventriculomegaly, in 6/26 (23%); microcephaly, in 12/24 (50%);
      beaked tectal plate, in 6/16 (38%); and flattened basiocciput, in 9/24 (38%). Of
      the 26 cases, 14 had normal amniotic fluid volume, five had oligohydramnios and
      seven had polyhydramnios. Fetuses with oligohydramnios had the highest incidence
      of concurrent fetal abnormalities; four of five fetuses (80%) with
      oligohydramnios had additional structural abnormalities. In the overall
      population, a very high incidence of other abnormalities was found; 17/26 (65%)
      cases showed additional abnormalities, some of which were not detected by
      ultrasound. Five fetuses had Meckel-Gruber syndrome and three had amniotic band
      syndrome. Only one of the 18 karyotypes obtained was abnormal (trisomy 18).
      Survival was very poor; only two of the eight who survived until birth are
      currently living.

PMID- 7719872
TI  - Fetal echocardiography during indomethacin treatment.
AB  - Fetal echocardiograms were evaluated in 315 studies performed in 107 fetuses
      exposed to indomethacin. In the majority of cases, the results of the fetal
      echocardiography study were within normal limits (74%). The most common abnormal
      phenomena were tricuspid valve regurgitation (10%), ductal constriction (6%),
      tricuspid valve regurgitation and ductal constriction (5%), an increased ductal
      velocity (2%), and other (3%). The difference between the prevalence of ductal
      constriction in the whole series of studies (11%) compared to the prevalence of
      ductal constriction per fetus (25%) (p < 0.001) suggests that this phenomenon was
      only temporary and disappeared when medication was discontinued. The mean
      gestational age for detection of tricuspid valve regurgitation was 27.7 +/- 2.8
      weeks and for ductal constriction, 30.9 +/- 2.1 weeks (t-test, p < 0.01). Trivial
      tricuspid valve regurgitation was detected at a mean of 26.7 +/- 2.2 weeks and
      significant tricuspid valve regurgitation at 29.6 +/- 2.3 weeks (t-test, p <
      0.01). We conclude that indomethacin treatment is relatively safe for the fetal
      heart. The most common side-effects are tricuspid valve regurgitation and ductal
      constriction. Tricuspid valve regurgitation may be detected before ductal
      constriction, but by itself it is not a contraindication for the continued use of
      indomethacin.

PMID- 7719873
TI  - Survival after fetal aortic balloon valvoplasty.
AB  - The pre- and postnatal course of a child surviving after successful intrauterine
      balloon aortic valvoplasty for critical aortic stenosis is described. She is now
      well at 4 years of age. A clearer understanding of the hemodynamics in such cases
      and improved catheter technology are necessary before this is advocated as a
      generally applicable technique. However, the outcome in this case is promising
      for the future of fetal interventional procedures.

PMID- 7719874
TI  - Natural history of echogenic foci within ventricles of the fetal heart.
AB  - Echogenic foci within the fetal heart have been reported in association with
      cardiac tumors and chromosomal abnormalities. They have been observed also as a
      normal variant of cardiac development. The goal of this study was to analyze the
      frequency, distribution and natural history of echogenic foci within the fetal
      heart. A total of 1139 patients referred for targeted ultrasound were studied.
      Patients with positive findings (presence of the echogenic foci) were referred
      for serial fetal echocardiographic examinations at 26-28 weeks and 34-36 weeks of
      pregnancy. Neonatal follow-up examinations were performed within the first 3
      months of life in 27 cases. Ventricular echogenic foci were seen in 3.6% of
      fetuses. The locations of the echogenic foci were as follows: left ventricle,
      92.8%; right ventricle, 4.8%; both ventricles, 2.4%. All fetuses had a normal
      karyotype. Echogenic foci remained present in all infants who underwent
      echocardiographic examination within the first 3 months of life. Echogenic
      intracardiac foci probably represent a normal variant of the development of
      papillary muscles and chordae tendinae.

PMID- 7719875
TI  - Increasing curvature of the normal fetal ductus arteriosus with advancing
      gestational age.
AB  - In order to determine whether the configuration of the normal fetal ductus
      arteriosus changes with increasing gestational age, we prospectively collected
      oblique transverse sonographic images of the fetal thorax through the ductus
      arteriosus. Scans from 240 consecutive normal fetuses with gestational age 20
      weeks or more were included in the study. The images were reviewed independently
      by two sonologists and the ductus arteriosus was graded as: (1) straight; (2)
      mildly curved (C-shaped, bending < 90 degrees from a straight line); or (3)
      markedly curved (C-shaped, bending > 90 degrees, or S-shaped). In cases where the
      two sonologists' gradings did not concur, the images were re-reviewed jointly by
      both sonologists and a grading was assigned by consensus. Forty-two cases were
      rejected, due to inadequate images. The ductus arteriosus was graded in 42
      fetuses aged 20-25.9 weeks, 48 at 26-31.9 weeks, 74 at 32-37.9 weeks, and 34 at
      38 weeks or more for a total of 198 cases. There was a significant trend to
      greater curvature with increasing gestational age (p < 0.0001). The frequency of
      a straight ductus arteriosus decreased steadily from 55% of fetuses aged 20-25.9
      weeks to 3% of fetuses at 38 weeks or older, while the frequency of marked
      curvature increased from 2% in the youngest age group to 56% in the oldest. The
      proportion with mild curvature showed little variation throughout gestation. In
      summary, the configuration of the ductus arteriosus is variable but tends to
      become more curved as pregnancy proceeds. Marked curvature or tortuosity of the
      ductus arteriosus should not be misinterpreted as a great vessel anomaly.

PMID- 7719876
TI  - Asthma, hypereosinophilia and peripheral neuropathy in a migrant farm worker.

PMID- 7719877
TI  - Allergy diagnosis revisited.

PMID- 7719878
TI  - Clinical efficiency of in vitro and in vivo tests for allergic diseases.
AB  - BACKGROUND: Specific serum IgE determination is widely used in the diagnosis of
      IgE-mediated allergic diseases but the relative merits of in vitro measurement of
      IgE antibody in comparison to in vivo skin tests are still debated. OBJECTIVE:
      The aim of this study was to investigate the clinical efficiency of a "second
      generation" technique for in vitro analysis of IgE antibody (Pharmacia CAP
      System). METHODS: Eighty-six patients with suspected inhalant and/or food
      allergies and 20 asymptomatic subjects for a total of 655 tests were evaluated.
      Sera with divergent results between in vitro and in vivo techniques were further
      analyzed by using ImmunoCAP inhibition and immunoblotting. For the calculation of
      sensitivity and specificity of both in vitro and in vivo tests we considered as
      true value (reference value) either the concordant results or, in case of
      discordance, the datum confirmed by ImmunoCAP inhibition or immunoblot (ie, vitro
      positive, vivo negative, ImmunoCAP inhibition positive; true result: positive).
      RESULTS: The obtained results demonstrate that the in vitro results correlate
      well in terms of specificity and sensitivity to this new reference standard. In
      particular a higher specificity for Pharmacia CAP System in comparison to in vivo
      skin prick test for grass pollens and a better sensitivity for mites and cat
      allergens were found. CONCLUSIONS: Our results suggest that the in vitro "second
      generation" testing provides reliable results in all clinical situations.

PMID- 7719879
TI  - Allergic rhinitis and recurrent epistaxis in children.
AB  - BACKGROUND: Many allergists, but few otolaryngologists, consider allergic
      rhinitis to be a common cause of nosebleeds in childhood. OBJECTIVE: To determine
      whether the two conditions are related, and whether epistaxis could be due solely
      to the local effects of nasal symptoms. METHODS: We studied 557 children who were
      referred consecutively to an allergy clinic of a children's hospital.
      Standardized questions were put to their accompanying parents, and skin prick
      tests were performed on the children, using common local inhalant allergens.
      RESULTS: On univariate analysis children who had both nasal symptoms and a
      positive skin test were found to have recurrent nosebleeds more frequently
      (20.2%) than had those with nasal symptoms on their own (9.9%), a positive skin
      test alone (3.4%), or neither (2.1%). Similarly, on logistic regression the odds
      ratio (OR) of nosebleeds was 3.3, 1.3, 1.65, and 1, respectively. Nosebleeds were
      more common in those who owned a dog or a cat and had a positive skin test to
      that species than in the remainder of the children (27.8% vs 10.8%). CONCLUSIONS:
      Allergic rhinitis is commonly associated with recurrent epistaxis. In many
      children it appears that nosebleeds are due to nasal symptoms plus some
      abnormality that is found in the atopic state: a disorder of hemostasis is
      suspected as the contributing factor.

PMID- 7719880
TI  - Comparison of Bricanyl Turbuhaler and Ventolin Rotahaler in children with asthma.
AB  - BACKGROUND: Pulmonary administration of beta 2-agonists by means of pressurized
      metered dose inhaler is widely used in the treatment of asthma. Young children
      have difficulties in using these inhalers unless a spacer device is used. To
      overcome this problem inspiratory flow driven dry powder inhalers have been
      developed. OBJECTIVE: The aim of this study was to compare the efficacy and
      safety of the two powder inhalers Bricanyl Turbuhaler (terbutaline sulphate 0.5
      mg t.i.d.) and Ventolin Rotahaler (salbutamol 0.4 mg t.i.d.) in 20 children 2 to
      6 years old with mild to moderate asthma. METHODS: The study had an open
      randomized crossover design with 1 week run-in without treatment and the two
      treatment periods of 2 weeks each. Efficacy was measured with peak expiratory
      flow determination, asthma symptom scores, and need for rescue medication.
      Adverse events were recorded. RESULTS: Peak expiratory flow increased
      significantly (P < .001) after both treatments. There were no statistically
      significant differences in peak expiratory flow, asthma symptom scores, need for
      extra inhalations, or adverse events between the devices. Most children (parents)
      preferred the Turbuhaler. CONCLUSION: Both Bricanyl Turbuhaler and Ventolin
      Rotahaler seem to be effective and well tolerated in the treatment of asthma in
      preschool children. Of special interest is that even the youngest children in the
      study group were able to use these powder inhalers.

PMID- 7719882
TI  - The Annals of Allergy, Asthma & Immunology.

PMID- 7719881
TI  - Mosquito bite anaphylaxis: immunotherapy with whole body extracts.
AB  - BACKGROUND: Adverse reactions to mosquito bites have been recognized for some
      time. These usually consist of large local swellings and redness, generalized
      urticaria, angioedema and less easily definable responses such as nausea,
      dizziness, headaches, and lethargy. METHODS: We report two patients who
      experienced systemic anaphylaxis from mosquito bites. Both were skin tested and
      given immunotherapy using whole body mosquito extracts. RESULTS: Skin testing
      using whole body mosquito extracts was positive to Aedes aegypti at 1/1,000
      weight/volume (wt/vol) in one patient and to Aedes aegypti at 1/100,000 wt/vol,
      and Culex pipiens at 1/10,000 wt/vol in the other. Skin testing of ten volunteers
      without a history of adverse reactions to mosquito bites was negative.
      Immunotherapy using these extracts resulted in resolution of adverse reactions to
      mosquito bites in one patient and a decrease in reactions in the other.
      CONCLUSIONS: Immunotherapy with whole body mosquito extracts is a viable
      treatment option that can play a role in patients with mosquito bite-induced
      anaphylaxis. It may also result in severe side effects and one must determine the
      benefit versus risks for each individual patient.

PMID- 7719883
TI  - Hypersensitivity pneumonitis from residential composting: residential composter's
      lung.
AB  - Hypersensitivity pneumonitis results when a susceptible individual is exposed to
      sufficient airborne material capable of inducing a systemic and pulmonary immune
      response. We describe a man who had all the classic manifestations of
      hypersensitivity pneumonitis but in whom the circumstances of sensitization,
      residential yard work with composted yard clippings, has not previously been
      reported. We call this new entity residential composter's lung.

PMID- 7719884
TI  - Allergic gastroenteropathy in children.
AB  - OBJECTIVE: To review the pathogenesis, symptoms, and treatment of
      gastrointestinal disorders linked to immunopathologic reactions associated with
      the ingestion of food antigens in infancy and childhood. DATA SOURCES: A
      computerized MEDLINE search was performed for the following topics: allergic
      colitis, allergic proctitis, eosinophilic gastroenteritis, eosinophilic colitis,
      cow milk intolerance, protein losing enteropathy, and malabsorption. This search
      was restricted to the English language and human subjects. Articles published
      between 1960 and 1993 were included as references. The textbooks which were used
      as references include: (1) Walker WA, et al, eds. Pediatric gastrointestinal
      disease; pathophysiology, diagnosis, management, Philadelphia: BC Decker, 1991;
      (2) Wyllie R, et al, eds. Pediatric gastrointestinal disease; pathophysiology,
      diagnosis, management, Philadelphia: WB Saunders, 1993; (3) Targan SR, et al,
      eds. Immunology & immunopathology of liver and gastrointestinal tract. Igaku
      Shoin, 1991; (4) Goldman H, et al, eds. Pathology of the gastrointestinal tract.
      Philadelphia: WB Saunders, 1992. CONCLUSION: The symptoms of allergic
      gastroenteropathy may be those of classic allergic reactions or present as
      symptom complexes that may include diarrhea, malabsorption, and protein-losing
      enteropathy. The immunopathogenesis of allergic gastroenteropathy is complex and
      is still not clearly understood. As our understanding of the gastrointestinal
      mucosal system evolves, we should be able to manage and care for the infants and
      children who suffer from this group of disorders better.

PMID- 7719885
TI  - Maternal-fetal transfer of immunoglobulins.
AB  - OBJECTIVE: The goal of this review is to summarize the current knowledge about
      the transfer of immunoglobulins from the mother to the fetus. Data obtained
      experimentally and clinically will be discussed, and intervention trials and
      options will be examined. DATA SOURCE: References are limited to the English
      language and to human data. Sources include computerized databases and
      bibliographies of recent articles and books. RESULTS: Electronmicroscopic studies
      have unveiled the passage route of IgG through the placenta. The placental in
      vitro perfusion system has become a valuable experimental model, with a crucial
      role in the preclinical evaluation of trials to manipulate the maternal-fetal
      passage of immunoglobulins. CONCLUSIONS: Immunoglobulins are transferred through
      the placenta in an active, selective and affinity-restricted process, which is Fc
      gamma receptor mediated and intracellular. Much work is still required to improve
      our ability to control the rate and the efficiency of this process, but the
      results of pioneering attempts have been encouraging.

PMID- 7719886
TI  - Bilateral red eyes in a patient infected with human immunodeficiency virus.

PMID- 7719887
TI  - Familial cold urticaria: a father and daughter with typical clinical and
      laboratory features.
AB  - BACKGROUND: Familial cold urticaria is a rare, autosomally dominant disease of
      interest to physicians treating urticarial-type diseases. OBJECTIVE: To describe
      two patients, a father and daughter with the characteristics of this disease and
      review the features that differentiate it from other cold-induced syndromes.
      METHODS: Both patients underwent a cold room challenge, a lesional skin biopsy,
      and an ice-cube test, P-K test and extensive laboratory studies pre- and post
      cold-room challenge. RESULTS: A careful history revealed winter outbreaks of
      erythematous, nonpruritic lesions occurring hours after cold air exposure since
      early childhood. Systemic symptoms included burning, chills, and arthralgias
      rather than the anaphylactic symptoms associated with acquired urticarias. Cold
      room challenge induced "non-urticarial" lesions after a delay of one-half to two
      hours. Lesional biopsy demonstrated polymorphonuclear infiltration with increased
      eosinophils. Ice-cube tests and P-K tests were negative, and laboratory studies
      were remarkable only for a rise in leukocytes and erythrocytic sedimentation rate
      after positive challenge. Abnormal serum proteins were not found. CONCLUSION:
      Familial cold urticaria is an inherited disease with distinct characteristics
      that distinguish it from acquired cold urticarias and other cold-induced
      syndromes. Most importantly, lesions occur with a delay after exposure to cold
      air and are not urticarial. Anaphylactic symptoms do not occur and abnormal serum
      proteins are not found.

PMID- 7719888
TI  - Specific IgE to Japanese cypress (Chamaecyparis obtusa) in patients with nasal
      allergy.
AB  - BACKGROUND: Japanese cedar (Cryptomeria japonica) is the most important pollen
      causing pollinois during spring. During recent years some patients' nasal
      symptoms have been getting worse after the Japanese cedar pollen season. Japanese
      cypress (Chamaecyparis obtusa) pollen is also observed in this period. The
      purpose of the study was to investigate the effect of Japanese cypress pollen and
      cross-allergenicity between Japanese cypress and Japanese cedar in patients with
      allergic rhinitis. METHODS: A total of 267 patients were enrolled in the study.
      IgE antibodies to both tree pollens were measured by the CAP RAST method. The
      results of the CAP RAST test were compared with those of skin tests. In order to
      compare cross-allergenicity between these two pollens, CAP RAST inhibition assay
      was carried out. RESULTS: The positive frequencies of Japanese cypress and
      Japanese cedar in 267 patients were 50.1% and 74.7%, respectively. A significant
      correlation (r = .765) was observed between the two tree pollens. There was good
      concordance (75%) between RAST and skin tests to Japanese cypress. The results of
      RAST inhibition assay indicated cross-allergenicity between these two pollens and
      species-specific allergens. CONCLUSION: Measurement of IgE antibody to Japanese
      cypress is useful for the diagnosis of pollinois during the spring.

PMID- 7719889
TI  - Clinical management strategies to maintain drug compliance in asthmatic children.
AB  - OBJECTIVE: Noncompliance with asthma medication is a common cause of treatment
      failure and may lead to unnecessary hospitalization and emergency care. This
      publication reviews factors associated with compliance with treatment regimens in
      general as well as with recommended asthma medications. General strategies
      (educational, organization, and behavioral) are reviewed with emphasis in
      behavioral strategies. These include reminders, tailoring, and contracting. STUDY
      SELECTION: A case report follows regarding a 9-year-old boy with severe asthma
      who was treated in a short-term inpatient asthma rehabilitation center and
      followed for 3 years as an outpatient. Specific clinical management strategies
      and techniques to maintain theophylline compliance are presented. CONCLUSION: A
      systematic approach emphasizing the use of behavioral strategies and drug
      monitoring can be helpful in promoting compliance with a therapeutic regimen.
      This may lead to a reduction in pulmonary morbidity and medical costs.

PMID- 7719890
TI  - Recurrent anaphylaxis due to unrecognized latex hypersensitivity in two
      healthcare professionals.
AB  - BACKGROUND: Anaphylaxis is a potentially fatal immediate-type reaction and
      intense effort may be required to identify the allergen responsible. In some
      cases, a "hidden" allergen may be responsible that is not apparent in spite of
      careful clinical assessment. OBJECTIVES: This report describes the assessment of
      two cases of anaphylaxis in which a search for an allergen was initially not
      conclusive and the diagnosis of idiopathic anaphylaxis was considered. METHODS:
      Two patients were evaluated by various physicians for anaphylaxis with no clear
      indication of a responsible allergen. Persistence in evaluation led to the
      identification of the allergen responsible. RESULTS: In two health care workers
      latex was identified as the "hidden" cause of anaphylaxis. This allergen had not
      been considered in either case in initial evaluations. Neither patient has had a
      recurrence of anaphylaxis since latex was identified as the cause of anaphylaxis.
      CONCLUSIONS: Although latex is widely recognized as a cause of anaphylaxis, it
      can still be unrecognized in some cases of recurrent anaphylaxis. Latex must be
      considered as a "hidden" cause of anaphylaxis, particularly in health care
      workers.

PMID- 7719891
TI  - House dust mite allergen content in two areas with large differences in relative
      humidity.
AB  - BACKGROUND: Striking differences in mite counts and mite-allergen levels have
      been documented between dwellings located at sea level and high altitude. Apart
      from relative humidity (RH), several other factors, ie, temperature, UV exposure,
      and altitude per se could account for this difference. OBJECTIVE: To evaluate
      whether RH by itself could influence mite infestation by comparing mite-allergens
      levels in two towns differing only with respect to RH. METHODS: We compared group
      I allergen content in two Moroccan towns: Casablanca, located on the seashore and
      Marrakech located at 1404 feet. Mean (+/- SD) RH in years 1990 and 1991 was 81.2
      +/- 2.9% in Casablanca and 56.0 +/- 7.6% in Marrakech. Mean annual temperatures
      were 17.7 +/- 4.0 degrees C and 20.2 +/- 6.4 degrees C in Casablanca and
      Marrakech, respectively. In each town, 20 asymptomatic subjects agreed to
      participate in the study. Their mattresses were vacuum-cleaned for a standardized
      duration (2 min/m2). Mite allergen-content was evaluated using monoclonal
      antibodies and ELISA and results expressed as micrograms of group I (Der pI+Der f
      I) allergens per gram of dust (micrograms/g dust). RESULTS: Mean (+/- SD) group I
      allergen level was 8.3 +/- 8.8 micrograms/g in Casablanca and 0.6 +/- 0.6
      micrograms/g dust in Marrakech, a difference that is highly significant (P =
      .001). In both areas, mean Der f I allergen level was low (0.7 +/- 0.5 and < 0.1
      micrograms/g dust, in Casablanca and Marrakech, respectively). CONCLUSION: This
      study shows that house dust mite allergen content in households depends on RH
      rather than on temperature.

PMID- 7719892
TI  - Cross-reactivity of alternate plant sources of latex in subjects with systemic
      IgE-mediated sensitivity to Hevea brasiliensis latex.
AB  - BACKGROUND: Previous studies have suggested that there is cross-reactivity in
      subjects sensitive to natural rubber proteins with other plant proteins such as
      banana, chestnut, and avocado. There are numerous other plants known to produce
      rubber including Parthenium argentatum and Ficus elastica. It is not known
      whether patients with IgE-mediated systemic reactions caused by the common source
      of natural rubber Hevea brasiliensis are also sensitive to the rubber-containing
      material from these other plant sources of latex. It is also not certain how much
      the allergenicity of latex made from Hevea brasiliensis can be reduced by
      extracting proteins from the sap since some proteins are tightly associated with
      the cis-1,4-polyisoprene. OBJECTIVE: In this study we investigated whether there
      would be cross-reactivity to other natural sources of latex in these patients.
      METHODS: Seven patients with histories of systemic type I hypersensitivity to
      latex products had strongly positive skin tests to Hevea brasiliensis latex from
      two different sources. These subjects were tested by the prick method for
      sensitivity to three other natural sources of latex. These included latex
      containing material from Parthenium-argentatum and Ficus elastica as well as
      washed and centrifuged rubber particles from Hevea brasiliensis sap. RESULTS: All
      subjects had negative skin tests to all dilutions of the rubber samples from
      these other natural sources of latex. CONCLUSION: These results suggest several
      potential sources of natural hypoallergenic latex that might be tolerated by
      latex-sensitive individuals.

PMID- 7719893
TI  - US asthma mortality: 1941 to 1989.
AB  - BACKGROUND: Asthma mortality in the United States has nearly doubled in the past
      10 years. An examination of long-term trends in United States asthma mortality
      places the current mortality rates in a historical perspective, identifies high
      risk groups for interventions, and may provide clues to the etiology of asthma
      mortality. METHODS: Asthma deaths for the population aged 5 to 34 years were
      abstracted from United States vital statistics reports for the period 1941
      through 1989. Race-specific and sex-specific mortality rates were age-adjusted to
      the 1989 estimate of the US population. RESULTS: Among the population aged 5 to
      34 years, three distinct periods of asthma mortality were observed: 1941 to 1964,
      1965 to 1977, and 1978 to 1989. From 1941 through 1964, nonwhites exhibited a
      gradual increase in asthma mortality rates; in contrast, whites showed no change
      in mortality rates. From 1965 through 1977, a marked decline in mortality rates
      was observed among both nonwhites and whites. From 1978 through 1989, asthma
      mortality increased with a near doubling in the mortality rates in both nonwhites
      and whites. Overall, nonwhites had mortality rates 4 times those of whites, with
      nonwhite males aged 15 to 34 at the greatest risk of death due to asthma. Age and
      sex differences in asthma mortality are also apparent. The population aged 15 to
      34 years generally had mortality rates greater than the population aged less than
      15 years. For the population aged 5 to 14 years, regardless of calendar year,
      females had lower mortality rates than males. Among the population aged 15 to 34
      years, females experienced twice the mortality rates of males prior to 1965;
      however, by the 1980s this relationship no longer existed. CONCLUSIONS: The
      asthma mortality rate for nonwhites was 4-fold higher than for whites, although
      the reported prevalence of asthma is less than 2-fold greater. The population
      aged 15 to 34 years had higher mortality rates than the population aged 5 to 14
      years despite exhibiting a lower prevalence of asthma. There are also gender
      differences in asthma mortality. These differences may be attributable to
      differences in asthma severity, or differences in disease management or reflect
      actual differences in mortality. These findings suggest that the search for clues
      to understand the increase in asthma mortality from 1978 to 1989 should include
      an attempt to understand why asthma mortality declined in the preceding decade
      from 1967 to 1977 as these may not be completely unrelated trends.

PMID- 7719894
TI  - Dose potency relationship of terbutaline inhaled via Turbuhaler or via a
      pressurized metered dose inhaler.
AB  - OBJECTIVE: The relative dose potency of cumulative doses of terbutaline sulfate
      inhaled via Turbuhaler and via a pressurized metered dose inhaler was estimated
      with respect to lung efficacy and systemic effect. METHODS: The study was an
      open, crossover, randomized, multicenter study including 31 adult patients with
      asthma [forced expiratory volume in one second (FEV1), 65% of predicted]. The
      patients inhaled terbutaline doses of 0.125, 0.125, 0.25, 0.5, 1.0, and 2.0 mg (a
      total of 4 mg) at 30-minute intervals. Lung function [FEV1, forced vital capacity
      (FVC), forced expiratory flow at 75% of FVC (FEF75%), and peak expiratory flow
      (PEF)], and systemic effect variables (serum potassium, tremor, pulse, blood
      pressure) were monitored prior to the first inhalation and 15 to 25 minutes after
      each inhaled dose. RESULTS: The mean relative dose potency of terbutaline inhaled
      via Turbuhaler compared with pressurized metered dose inhaler was 1.5 (95%
      confidence interval: 1.2 to 1.8) with respect to FEV1 and serum potassium,
      respectively. The corresponding relative dose potencies for PEF, FVC, and FEF75%
      were 1.0, 1.2, and 1.6, respectively, with no statistically significant
      difference between the two devices. No differences between the devices were
      evident with regard to blood pressure and pulse. CONCLUSION: The results suggest
      that Turbuhaler is more efficient in the delivery of inhaled terbutaline to the
      lungs compared with the conventional pressurized metered dose inhaler.

PMID- 7719895
TI  - Differences in lymphocyte proliferative responses to food antigens and specific
      IgE antibodies to foods with age among food-sensitive patients with atopic
      dermatitis.
AB  - BACKGROUND: Clinical symptoms of patients with food-sensitive atopic dermatitis
      often improve with increasing age. OBJECTIVE: To investigate this tendency and
      the underlying mechanism. METHODS: We selected and divided 194 food-sensitive
      atopic dermatitis patients into three age groups. The proliferative responses of
      peripheral blood mononuclear cells (PBMCs) to food antigens and specific IgE
      antibodies to foods then were evaluated with respect to age. We also followed up
      55 food-sensitive patients with atopic dermatitis and examined their improvement
      ratio after 1 year. Further, we investigated changes in lymphocyte proliferative
      responses to food antigens and specific IgE antibodies to foods in food-sensitive
      patients with atopic dermatitis during elimination diets. RESULTS: Proliferative
      responses of PBMCs to ovalbumin of patients in the over 6-years-old group were
      significantly (P < .05) lower than those of the less than 1-year-old group.
      Proliferative responses of PBMCs to bovine serum albumin of patients in the over
      6-years-old group were significantly (P < .05) lower than those in the 1 to 5
      year-old group and in the less than 1-year-old group. RAST values for hen egg in
      the over 6-years-old group were significantly (P < .05) lower than those for the
      less than 1-year-old group. Improvement was shown by 13 of the 33 hen egg
      sensitive patients with atopic dermatitis, an improvement ratio of 39%, and by 9
      of the 22 cow milk-sensitive patients with atopic dermatitis, an improvement
      ratio of 41%. Proliferative responses of PBMCs to food antigens in food-sensitive
      patients with atopic dermatitis decreased rapidly after patients were placed on
      elimination diets. CONCLUSION: The PBMC proliferative responses to food antigens
      and RAST values were higher for young children and lower for older ones who
      suffered from food-sensitive atopic dermatitis. Oral tolerance, in addition to
      the development of digestive and absorptive functions, may be responsible for
      these immunologic changes.

PMID- 7719896
TI  - Spectrum of presentation of paradoxical vocal cord motion in ambulatory patients.
AB  - BACKGROUND: Paradoxical vocal cord motion (PVCM) frequently masquerades as
      asthma. Atypical presentations of asthma or situations in which asthma does not
      respond to traditional therapies mandate the consideration of PVCM in the
      differential diagnosis. OBJECTIVE: Evaluate the demographics and spectrum of
      presentation of PVCM in an ambulatory outpatient population. METHODS:
      Retrospective survey of medical records of 164 consecutive patients (86 males, 78
      females) who underwent fiberoptic rhinolaryngoscopy over a 3-year period.
      RESULTS: Twenty patients (16 females, 4 males) with PVCM diagnosed by direct
      visualization were identified. Mean age at diagnosis was 33 years (range, 14-58
      years). Asthma was the most common presenting diagnosis (15/20, 75%), while the
      remaining 25% had other unusual presentations including two patients (10%) with
      PVCM masquerading as anaphylaxis. When PVCM masqueraded as asthma, 44% of those
      patients were inappropriately treated with oral steroids. Nine patients (45%) had
      a readily identifiable psychologic trigger of their PVCM. CONCLUSIONS: Our data
      confirm previous observations indicating that PVCM is most common in young
      females and is often associated with psychologic problems. PVCM frequently
      masquerades as asthma, resulting in overtreatment with corticosteroids. PVCM may
      also masquerade as stridor, resulting in mimicry of anaphylaxis in the
      appropriate clinical setting. Thus, PVCM should be considered in any patient
      presenting with atypical upper and lower respiratory tract symptoms.

PMID- 7719897
TI  - Dose-ranging comparative evaluation of cetirizine in patients with seasonal
      allergic rhinitis.
AB  - BACKGROUND: Cetirizine, an H1-receptor antagonist, has been studied for the
      relief of seasonal and perennial allergic rhinitis, one of the most common
      allergic disorders in the United States. Unlike newer antihistamines that can
      have interactions with other medications, including some macrolide antibiotics
      and some antifungal agents, cetirizine has not been associated with adverse
      events consequent to interaction with drugs that depend on hepatic enzymes for
      their metabolism. OBJECTIVE: The efficacy of cetirizine was compared with that of
      previous pharmacologic therapy in patients with allergic rhinitis. Patients were
      allowed to dose-titrate to achieve the optimal therapeutic response. METHOD: This
      was a dose-ranging, open-label, multicenter, 2-week clinical trial of 296
      patients with allergic rhinitis. All patients were initially treated with 5 mg of
      cetirizine and allowed to dose-titrate up to 20 mg/d, depending on symptom
      severity. RESULTS: Symptom severity scores decreased sharply within the first 24
      hours of cetirizine therapy and continued to improve. Symptoms showing the
      greatest immediate improvement were rhinorrhea, itching nose, sneezing, itching
      eyes, and watery eyes, with nasal congestion and postnasal drip improving more
      slowly. By study completion, 13.4% of patients remained on the initial cetirizine
      dose of 5 mg/d, 31.1% increased dosage to 10 mg/d, and 41.6% increased their dose
      to 15 or 20 mg/d. According to physician global evaluations, 82% of patients
      showed improvement on cetirizine, while 75% of patients indicated that cetirizine
      was better than or equal to previous single-agent therapy, including those who
      had previously used terfenadine (75%), astemizole (80%), or other antihistamines
      (73%), and by 58% on previous therapy with antihistamine-decongestant combination
      drugs. Side effects were minimal and no different from those observed in other
      studies of cetirizine. CONCLUSION: Dose titration of cetirizine may allow for
      greater efficacy and quality of life, especially for patients with refractory
      symptoms of allergic rhinitis in whom therapy with single-dose antihistamines has
      failed.

PMID- 7719898
TI  - Allergy to additive to infant cereal.

PMID- 7719900
TI  - Intestinal immune response of volunteers ingesting a strain of enteroadherent
      (HEp-2 cell-adherent) Escherichia coli.
AB  - Enteroadherent Escherichia coli (EAEC) strains identified by adherence to HEp-2
      tissue culture cells have been incriminated epidemiologically as important
      etiologic agents of diarrheal disease in both adult travelers and children in
      developing countries. One strain, JM 221, with no recognized E. coli virulence
      characteristics other than adherence to HEp-2 cells, caused diarrhea in 5 of 16
      volunteers ingesting it. We studied the secretory immunoglobulin A (sIgA)
      responses to EAEC JM 221 of five volunteers with diarrhea and five volunteers who
      remained healthy after challenge. sIgA was extracted from stools obtained
      prechallenge and 7 days postchallenge. Total sIgA was standardized for all
      specimens. Specific sIgA titers were determined by dot blotting with the
      following JM 221 antigens: water-extractable surface antigens, whole cells,
      lipopolysaccharides, and outer membrane proteins. All five subjects who became
      ill had fourfold or greater rises in titers against each of the four antigens.
      The five subjects who remained healthy following challenge did not exhibit
      significant rises in titers to any JM 221 antigens, but their mean titers were
      significantly higher than the mean prechallenge titers of the volunteers with
      diarrhea, suggesting that high intestinal sIgA titers may be protective. The
      significant increases in intestinal antibody against JM 221 in the subjects who
      became ill is further evidence of the enteropathogenicity of EAEC strains.

PMID- 7719901
TI  - Comparison of CD4 cell count by a simple enzyme-linked immunosorbent assay using
      the TRAx CD4 test kit and by flow cytometry and hematology.
AB  - Measurement of CD4 T-lymphocyte levels is clinically useful in monitoring immune
      status in a number of conditions, including human immunodeficiency virus (HIV)
      infection, in which the absolute CD4 count is used to guide therapy. The absolute
      CD4 count is obtained by multiplying the results of the leukocyte count and the
      differential with a hematology cell counter and the percentage of CD4+ T
      lymphocytes determined by flow cytometry. These techniques require expensive,
      complex instrumentation, and interlaboratory results are difficult to standardize
      and reproduce. The rapid growth of HIV infection worldwide has increased the need
      for more-reproducible and cost-effective methods for CD4 T-cell monitoring. The
      TRAx CD4 test kit is based on a novel adaptation of conventional enzyme-linked
      immunosorbent assay (ELISA) and permits the simple quantitation of total CD4
      protein from whole-blood lysates. In this study, the relationship between total
      CD4 protein measured in units per milliliter (TRAx) and in cells per microliter
      (flow cytometry and hematology) was defined in a multisite clinical study using
      linear regression analysis. Data from 230 HIV-seronegative and 321 HIV
      seropositive specimens were used to calibrate the TRAx assay recombinant CD4
      standards and controls in equivalent CD4 T lymphocytes per microliter (cells per
      microliter). The calibration of the TRAx CD4 assay in cells per microliter was
      validated with a second group of specimens from 17 healthy volunteers and 20 HIV
      seropositive patients which were collected and tested under strictly controlled
      conditions intended to minimize the effects of specimen aging on the results of
      the reference method. These data were also used to estimate the variability of
      absolute CD4 count by cytometric methods as well as the precision of the TRAx CD4
      result after it was calibrated in cells per microliter. Overall, correlations
      between the two methods ranged from 0.87 to 0.95. Additional studies demonstrated
      that the contribution of CD4 protein from monocytes and any soluble CD4 in sera
      are negligible in the TRAx assay and do not significantly affect results. This
      new method represents a promising alternative to absolute CD4 T-cell enumeration
      by flow cytometry and hematology.

PMID- 7719899
TI  - Laboratory evaluation of the inflammatory myopathies.
AB  - The laboratory plays an important role in the diagnosis, evaluation, and
      classification of the heterogeneous group of diseases known as the IIM, which are
      characterized by chronic muscle inflammation. Serial measurements of the levels
      of muscle-derived enzymes in serum are the traditional laboratory studies used to
      follow the clinical course of patients with IIM, although other laboratory tests
      can also be useful in assessing myositis disease activity. Several markers of
      immune system activation, including cytokines and lymphocyte markers, show
      promise as possibly more sensitive measures of myositis disease activity.
      Discovery of a unique group of MSAs over the past decade has provided an
      immunologic basis for defining relatively homogeneous subsets of patients who
      share similar clinical features, disease courses, and responses to therapy.
      Future investigations of novel immunologic activation markers, as well as the
      cloning and expression of target autoantigens of the MSAs, should allow better
      diagnostic assays, enhanced prognosis, and a better understanding of the
      pathogenesis of these disorders.

PMID- 7719902
TI  - Determination of normal human fetal immunoglobulin M levels.
AB  - Immunoglobulin M (IgM) levels were measured in 198 cord blood samples from 192
      apparently normal pregnancies from 24 weeks of gestation to term. Simple linear
      regression analysis yielded a standard curve for IgM development during pregnancy
      showing a 0.5 mg/dl increase in IgM per week of gestation. This curve allows the
      comparison of fetal IgM levels from pregnancies considered to be at risk for
      intrauterine infection.

PMID- 7719903
TI  - Elevated levels of circulating tumor necrosis factor alpha in human
      immunodeficiency virus type 1-infected Africans living in Sweden.
AB  - Elevated levels of tumor necrosis factor alpha in serum were found in human
      immunodeficiency virus type 1 (HIV-1)-infected Africans to a higher extent than
      in matched HIV-1-infected Caucasians, both groups living in Sweden. The results
      suggest that factors not related to the environment contribute to enhanced
      synthesis of tumor necrosis factor alpha in HIV-1-infected patients.

PMID- 7719905
TI  - Investigation of cross-reactions against Trichinella spiralis antigens by enzyme
      linked immunosorbent assay and enzyme-linked immunoelectrotransfer blot assay in
      patients with various diseases.
AB  - Data regarding cross-reactions against Trichinella spiralis in humans are scarce
      and controversial. For this reason, we tested serum samples from patients with
      typhoid fever, brucellosis, toxoplasmosis, amoebiasis, cysticercosis,
      trichocephaliasis, ascariasis, and onchocerciasis against an antigenic extract of
      T. spiralis infective larvae in an enzyme-linked immunosorbent assay (ELISA) and
      an enzyme-linked immunoelectrotransfer blot (EITB) assay. All except one serum
      sample from the group of patients with onchocerciasis were negative in the ELISA;
      in the EITB assay, only faint bands were observed with the samples from patients
      with onchocerciasis and ascariasis and negative results were obtained with the
      samples from patients with other diseases. In conclusion, cross-reactions were
      found only in the groups of patients with other nematode infections and were of
      very low magnitude, most of them virtually negative.

PMID- 7719904
TI  - Time to peak serum antibody response to influenza vaccine.
AB  - The time to the appearance of a peak serum antibody response to influenza virus
      vaccine is not clearly defined. We compared the most commonly used time intervals
      described in the literature--4 and 6 weeks after vaccination. We studied 118
      elderly patients from three different geographic sites. The 1992 to 1993
      trivalent inactivated influenza virus vaccine containing influenza virus
      A/Beijing/353/89 (H3N2), influenza virus A/Texas/36/91 (H1N1), and influenza
      virus B/Panama/45/90 was used. No statistically significant differences were
      found at the 4- and 6-week intervals after vaccination.

PMID- 7719906
TI  - Serum antibody response to proteins of Moraxella (Branhamella) catarrhalis in
      patients with lower respiratory tract infection.
AB  - We searched for antibodies against Moraxella (Branhamella) catarrhalis proteins
      in the sera of patients with lower respiratory tract infection. Sera from 48
      patients with M. catarrhalis and 39 patients without M. catarrhalis in their
      lower respiratory tract specimens were studied by a gel electrophoresis
      immunoperoxidase technique; sera from 23 healthy adult blood donors were also
      included. Immunoglobulin G (IgG) antibodies against a 28-kDa protein were found
      significantly more frequently in patients with M. catarrhalis in lower
      respiratory tract specimens (71%) than in patients without M. catarrhalis in
      lower respiratory tract specimens (28%) or healthy adult blood donors (22%).
      Seroconversion, from the acute to the convalescent stages, occurred in at least
      eight patients with M. catarrhalis and in one patient without detectable M.
      catarrhalis. IgG antibodies against other M. catarrhalis proteins were found in
      most sera, including those obtained from blood donors. By adsorption experiments
      the 28-kDa protein was demonstrated to be surface exposed. IgM antibodies against
      an 85-kDa protein were found in serum from one patient from whom M. catarrhalis
      and Streptococcus pneumoniae were isolated from the lower respiratory tract,
      while IgA antibodies against M. catarrhalis proteins could not be detected in any
      serum specimen.

PMID- 7719907
TI  - Quantitative reverse transcription-PCR analysis of Legionella pneumophila-induced
      cytokine mRNA in different macrophage populations by high-performance liquid
      chromatography.
AB  - Cytokine production in macrophages infected by bacteria is critical for the
      course of infection. However, it is not known how infection of macrophages with
      opportunistic bacteria leads to cytokine production in different populations of
      cells. Since it is possible that cytokine genes may be differentially regulated
      by attachment rather than by active infection, the levels of various cytokine
      mRNAs were measured in alveolar macrophages (AMs), peritoneal resident
      macrophages (RMs), and peritoneally elicited macrophages (EMs) interacting with
      Legionella pneumophila by using cytochalasin D-treated macrophages and a newly
      developed quantitative reverse transcription-PCR procedure with high-performance
      liquid chromatographic analysis to determine cytokine mRNA formation. Increased
      levels of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha,
      granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory
      protein 2 mRNAs were quantitated in the macrophages responding to L. pneumophila
      attachment in vitro. Using this technique, we showed that the three different
      macrophage populations responded differently to bacterial attachment. We found
      that the levels of IL-6 and granulocyte-macrophage colony-stimulating factor
      mRNAs induced by the attachment of L. pneumophila to AMs were significantly lower
      than the levels in RMs but similar to the levels in EMs. Furthermore, the levels
      of MIP-2 mRNA in the AMs were found to be higher than those in the RMs, but
      similar levels were found in EMs. IL-1 beta mRNA levels were higher in both AMs
      and RMs than in EMs, but tumor necrosis factor alpha levels were not different
      among the three macrophage populations examined. Thus, the responses of
      macrophages to bacterial attachment in terms of cytokine mRNA levels were readily
      quantitated by the reverse transcription-PCR assay. However, the results obtained
      showed different levels of responsiveness of distinct macrophage populations to
      L. pneumophila attachment, and this could be related to the characteristic nature
      of the macrophage type examined.

PMID- 7719908
TI  - Stability of cytomegalovirus antibodies in plasma during prolonged storage of
      blood components.
AB  - Cytomegalovirus (CMV) antibody testing is currently limited by manufacturers'
      guidelines to specimens stored for 7 days or less. We examined the stability of
      CMV antibodies in plasma from platelets and whole-blood units during storage
      using a rapid, automated, recombinant protein-based immunoassay which
      qualitatively detects total antibody to human CMV. Testing of single-donor
      apheresis platelets was performed on baseline serum and platelet-free plasma and
      on platelet-free plasma 8 days later. Indeterminate, positive, and negative CMV
      antibody results were maintained over time for 97% (75 of 77) of the platelet
      specimens. For whole-blood units, initial testing of donor serum and plasma
      obtained from erythrocyte segments took place within 7 days of phlebotomy.
      Indeterminate, positive, and negative CMV antibody results were maintained on
      subsequent analyses performed on erythrocyte segments at 2, 4, 6, and 8 weeks for
      100% of whole-blood specimens. An important potential benefit of CMV antibody
      testing of stored platelets and blood is the elimination of a costly, dedicated,
      CMV-negative inventory. The study suggests that CMV antibody testing can be
      conveniently and reliably performed on blood components over the entire storage
      period.

PMID- 7719909
TI  - Antigenicity and immunogenicity of recombinant glutamate-rich protein of
      Plasmodium falciparum expressed in Escherichia coli.
AB  - A recombinant Plasmodium falciparum glutamate-rich protein (GLURP) was produced
      in Escherichia coli as a nearly full-length protein. In order to map
      immunodominant regions on GLURP, the nonrepetitive amino-terminal region (R0) as
      well as the central repeat region (R1) and the carboxy-terminal repeat region
      (R2) were also produced as separate products. All four purified gene products
      reacted specifically with serum samples from adults living in an area of Liberia
      where malaria is holoendemic. It appears that the human immune response against
      GLURP is primarily directed against the R2 region because 94% of the serum
      samples reacted with this region in an immunoassay. Antibody reactivity against
      the R0 region was also observed in 75% of the serum samples, while the R1 region
      showed only weak antibody-binding activity. When the nearly full-length GLURP
      molecule was adsorbed to Al(OH)3 it was found to be immunogenic in mice. In these
      experiments, the antibody response was almost exclusively directed against the R2
      region. When anti-GLURP sera were obtained from rabbits immunized with the three
      regions, R0, R1, and R2, respectively, they recognized in immunoprecipitation
      experiments authentic GLURP from P. falciparum grown in vitro. These results
      demonstrate that GLURP produced in E. coli can induce a humoral immune response
      against GLURP derived from blood-stage parasites.

PMID- 7719910
TI  - Human immune response against outer membrane proteins of Moraxella (Branhamella)
      catarrhalis determined by immunoblotting and enzyme immunoassay.
AB  - The role of Moraxella (Branhamella) catarrhalis as a respiratory tract pathogen
      is increasingly recognized. We looked at the human immune response against
      individual outer membrane proteins of M. catarrhalis and against the 81-kDa CopB
      protein, which has previously been shown to be a target for protective
      antibodies. Paired serum samples from six elderly patients with pneumonia were
      tested by Western blot (immunoblot) analysis by using outer membrane vesicles of
      M. catarrhalis 035E as antigen. All of the six convalescent-phase serum samples
      reacted with a protein which migrated at the position of the CopB protein and
      with a high-molecular-weight protein of M. catarrhalis; three serum samples also
      reacted with a 34-kDa outer membrane protein. Paired serum samples from 18
      patients, 10 of which had M. catarrhalis infection on the basis of previous
      serology results, were tested by enzyme immunoassay (EIA) with the CopB protein
      and whole cells of M. catarrhalis 035E as antigens. Nine patients showed a
      significant rise in EIA titer between acute- and convalescent-phase sera when
      whole bacterial cells were used as antigens. Six (67%) patient samples that were
      positive by the EIA with the whole-cell antigen were also positive by the EIA
      with the CopB antigen, and six of nine patient samples negative by the EIA with
      the whole-cell antigen were also negative by the EIA with the CopB antigen. These
      results suggest that both the CopB and a high-molecular-weight protein are major
      targets of the immune response against M. catarrhalis, and further studies with
      greater amounts of patient materials are needed to elucidate the usefulness of
      CopB as an antigen in etiologic studies.

PMID- 7719911
TI  - A simple method for the propagation of cervical lymphocytes.
AB  - Local immune function is most likely a key influence in the establishment of
      human papillomavirus infections and its subsequent disease. Unfortunately, little
      information is known about local cervical immunity, and even less is known about
      human papillomavirus immunoreactivity. In addition, studies of local
      immunoreactivity have been hampered by the technical difficulty in obtaining
      cervical lymphocytes. The objective of the present study was to develop a simple
      method for the propagation of cervical lymphocytes from biopsy-size specimens.
      Cervical tissue was obtained from women undergoing a hysterectomy. Cervical
      samples measuring approximately 3 by 5 by 2 mm were minced and divided into two
      portions. One portion was digested by standard digestion methods and density
      gradient lymphocyte separation. The sample was then immunocharacterized for CD4
      and CD8 cells by flow cytometry. The other portion was minced into 1-mm3
      sections, and each section was placed into a separate well with tissue culture
      medium and interleukin-2. Lymphocyte counts and immunophenotypic analysis were
      performed after 18 to 20 days in culture. After 18 to 20 days in culture, the
      analysis demonstrated that this method of direct lymphocyte culture from a biopsy
      specimen yielded approximately 1 x 10(6) to 5 x 10(6) lymphocytes.
      Immunophenotypic studies of the digested sample at day 0 revealed CD4-to-CD8
      ratios of between 0.7:1 and 3.5:1, and at days 18 to 20 they revealed ratios of
      between 2.3:1 and 98:1. In summary, we developed a simple technique for
      propagating cervical lymphocytes from small tissue samples for the study of the
      local immune response. Studies are under way to optimize lymphocyte growth and to
      preserve CD8 populations.

PMID- 7719913
TI  - Prevalence of antibodies against Borrelia species in patients with unclassified
      uveitis in regions in which Lyme disease is endemic and nonendemic.
AB  - We studied 93 patients with unclassified uveitis from two regions in Japan
      (Hokkaido and Kanagawa) to assess the contribution of Borrelia species to this
      condition. The seroprevalence of antibody to Borrelia species was higher in
      patients from Hokkaido than in those from Kanagawa. The unclassified uveitis of
      seropositive patients was probably a complication of Lyme borreliosis since (i)
      the antibody titers were as high as those in clinically diagnosed Lyme disease
      patients, (ii) healthy controls from Hokkaido showed low seroprevalence in
      contrast with unclassified uveitis patients from Hokkaido, and (iii) the reaction
      pattern of antibodies in sera from patients with unclassified uveitis was the
      same as that in patients with Lyme disease. This is the first report to reveal
      the high risk of Lyme borreliosis in patients with unclassified uveitis in
      regions endemic for Lyme disease. In case of unclassified uveitis as well as in
      cases of inflammatory disease of unknown origin, Lyme disease should be taken
      into consideration, especially in regions in which Lyme diseases is endemic, even
      if it is reported only in animals.

PMID- 7719912
TI  - Immunoglobulin gene sequence analysis to further assess B-cell origin of multiple
      myeloma.
AB  - To further characterize the B-cell origin of multiple myeloma, our laboratory
      performed immunoglobulin gene sequence analyses of four cases of myeloma (three
      immunoglobulin A and one immunoglobulin G). Three tumors expressed VH3 genes and
      one expressed a VH1 gene, while the light chains included two V lambda and one V
      kappa III; one light chain was not isolated. The closest homology to published
      germ line genes ranged from 91 to 97%. In two cases, the expressed VH genes were
      compared with the putative germ line precursor VH genes isolated from autologous
      granulocyte DNA and appeared to have mutated randomly from the germ line gene. By
      sequencing multiple clonal isolates from each tumor sample, we found no evidence
      for ongoing mutation in three cases; in one case, however, clonotypic
      heterogeneity was evident. The analysis of DH- and JH-region genes revealed (i)
      limited or absent N nucleotide insertions (two of four cases), (ii) the presence
      of a DH-JH junction resulting from sequence overlap between the DH and JH genes
      (one of four cases), (iii) the absence of somatic mutations (two of four cases),
      and (iv) restricted JH gene usage of a JH6 polymorphism (three of four cases).
      These analyses of DH and JH genes suggest that multiple myeloma, similar to what
      has been proposed for chronic lymphocytic leukemia, may derive from B cells which
      have rearranged during fetal development rather than during adult life.

PMID- 7719914
TI  - Dilution assessment of cervicovaginal secretions obtained by vaginal washing for
      immunological assays.
AB  - Local immunological defense mechanisms in the cervicovaginal mucosa currently
      remain incompletely defined, especially from a quantitative point of view.
      Addition of an inert substance, lithium chloride (LiCl), into the washing buffer
      used to carry out the vaginal washing for collecting cervicovaginal secretions
      and measurement of its concentration with a flame absorption spectrophotometer,
      before and after the specimen is sampled, permits the quantification of the
      volume of cervicovaginal secretions collected and the approximation of the
      dilution factor of a soluble component introduced by the washing. Lithium, at a
      concentration of 10 mM, gives the best precision of measurement and has no effect
      on the results of the immunoassays. In a population of 27 nonpregnant women (age
      range, 18 to 45 years), the volume of cervicovaginal secretions collected by
      vaginal washing with 3 ml of LiCl-phosphate-buffered saline was 12% +/- 3.2%
      (mean +/- standard deviation) of the total volume and showed large
      interindividual variations (range, 5.6 to 18.8%); the mean dilution factor of a
      soluble component from the vaginal secretions was 9.9% +/- 2.8% (range, 6.3 to
      18.8%). According to the date of the menstrual cycle, the mean volume of
      collected cervicovaginal secretions was significantly increased in the luteal
      phase in comparison with the follicular phase; conversely, the mean dilution
      factor of a soluble component was more important in the follicular than in the
      luteal phase. These features strengthen the need to quantify accurately the
      dilution factor introduced by vaginal washing when studying cervicovaginal
      immunity.

PMID- 7719915
TI  - Effect of malnutrition in Ecuadorian children on titers of serum antibodies to
      various microbial antigens.
AB  - The titers of serum antibodies to natural infection with enteric and respiratory
      pathogens, to a food antigen and to tetanus and diphtheria toxoid were evaluated
      by enzyme-linked immunosorbent assay in 1,554 Ecuadorian children younger than 5
      years of age. The nutritional status of the children was assessed by
      anthropometry and measurement of biochemical status indicators. The children were
      enrolled in a representative national nutrition and health survey. Antibody
      titers were analyzed as a function of the nutritional status of the children. For
      12 of 14 antibody concentrations tested, underweight children showed lower
      antibody titers than did control children. The difference was statistically
      significant for antibody to both T-cell-dependent antigens (tetanus toxoid,
      rotavirus, respiratory syncytial virus) and T-cell-independent antigens
      (lipopolysaccharide, polyribosyl-ribitol phosphate, capsular polysaccharide).
      When children with a recent episode of diarrhea were excluded, many of the
      differences remained significant. When these children were further classified by
      age, only difference in titers of antibodies to respiratory syncytial virus and
      tetanus toxoid remained significant. No statistically significant difference was
      detected between underweight and control children with respect to protective
      antibody levels to four bacterial antigens. Anemic children showed significantly
      lower antibody levels to both T-cell-dependent and T-cell-independent antigens
      than did control children, and a higher proportion of anemic children had
      diphtheria antitoxin below a conservatively defined protective antibody level. No
      major differences in antibody titers were seen between children with different
      retinol and zinc concentrations in serum.

PMID- 7719916
TI  - Serotypes and subtypes of Neisseria meningitidis: results of an international
      study comparing sensitivities and specificities of monoclonal antibodies.
AB  - An international study supported by the World Health Organization comparing
      monoclonal antibodies for serotyping and serosubtyping of Neisseria meningitidis
      strains was performed and the results were assessed in 1992. A collection of 6
      serotype-specific (1, 2a, 2b, 4, 14, and 15) and 12 serosubtype-specific (P1.1,
      P1.2, P1.4, P1.5, P1.6, P1.7, P1.9, P1.10, P1.12, P1.14, P1.15, and P1.16)
      monoclonal antibodies was provided to 11 participating laboratories throughout
      the world. Monoclonal antibodies were tested on 85 Neisseria meningitidis strains
      with known reference results. Whole-cell enzyme-linked immunosorbent assay was
      used for analysis in 10 of 11 laboratories. The sensitivities and specificities
      of individual serotype- and subtype-specific monoclonal antibodies were
      evaluated. Differences in individual laboratories and with individual monoclonal
      antibodies were assessed. Relatively large differences in sensitivities were
      achieved in individual laboratories. On the contrary, the specificities remained
      at high levels in all laboratories. The sensitivities of serotype-specific
      monoclonal antibodies ranged from 72.0 to 100%. Individual serosubtype-specific
      monoclonal antibodies showed sensitivities ranging from 64.1 to 98.1%. The most
      frequent reason for the incorrect results obtained with the monoclonal antibodies
      were false-negative results. The collaborative study demonstrated that some
      monoclonal antibodies are not very sensitive. Another study to define the most
      suitable monoclonal antibodies is planned.

PMID- 7719917
TI  - Changes in CD45 isoform expression vary according to the duration of T-cell
      memory after vaccination.
AB  - Healthy young (< 40 years) and elderly (< 60 years) adults were immunized with
      the 1992-1993 preparation of trivalent influenza vaccine, and changes in CD45
      isoform expression on peripheral blood lymphocytes were measured in the pre- and
      postvaccination periods. Fluorescence-activated cell sorter analysis was used to
      study T-cell subsets in fresh peripheral blood lymphocytes (day 0) and after 6
      days of culture with live influenza virus. We have reported previously that the
      interleukin-2 response to the stimulating strain of virus, A/Texas/16/89, did not
      decline until 26 weeks postvaccination. In ex vivo CD4+ subsets, this interleukin
      2 response was paralleled by a > 10% increase in the proportion of cells
      expressing the CD45RO+ phenotype following vaccination (p < 0.0001). In vitro
      stimulation had no effect on CD4+ subsets prior to vaccination but, after
      vaccination, was associated with a > 10% increase in CD45RA+RO+ cells (P <
      0.0001). In addition, we have identified a change in the population of cells that
      express a CD45 isoform that is neither CD45RA nor CD45RO (CD45RA-RO-). At 26
      weeks postvaccination, the proportion of CD45RA-RO- cells in ex vivo CD4+
      peripheral blood mononuclear cells increased by approximately 15% from that
      measured at the earlier postvaccination time points (P < 0.0001). In vitro
      stimulation with influenza virus resulted in a further 20% increase in the
      proportion of CD45RA-RO- cells (P < 0.0001). The CD45RA-RO- phenotype may
      identify a population of cells undergoing apoptosis (programmed cell death) that
      limits the duration of helper T-cell (CD4+) memory after vaccination.

PMID- 7719918
TI  - Sensitivity of immune complex-dissociated p24 antigen testing for early detection
      of human immunodeficiency virus in infants.
AB  - Several investigators have suggested that early diagnosis of human
      immunodeficiency virus (HIV) infection in infants could be accomplished with a
      modified, more-sensitive, acid-dissociated p24 antigen enzyme-linked
      immunosorbent assay (ELISA) technique (p24 antigen immune complex dissociation
      [ICD]). We compared detection of HIV infection by HIV culture, PCR, and p24
      antigen ICD assays in 46 infants by using samples collected independently. The
      detection sensitivity of the p24 antigen ICD assay was 0% with cord blood samples
      (2 HIV-positive infants), 38% with plasma samples from infants under 3 months of
      age (8 HIV-positive infants), and 58% overall (12 HIV-positive infants). By
      contrast, the sensitivities of HIV culture and PCR were 50% for cord blood
      samples, 75% for plasma samples from infants under 3 months of age, and 83%
      overall. These results indicate that the p24 antigen ICD does not offer the
      sensitivity necessary for this assay to be used as an indicator of HIV infection
      in infants.

PMID- 7719919
TI  - Enhancement of natural killer cell activity in human immunodeficiency virus
      infected subjects by in vitro treatment with biologic response modifier OK-432.
AB  - A decrease in natural killer (NK) cell function has been related to the
      progression of human immunodeficiency virus (HIV) infection. In the present
      study, we assessed the ability of a streptococcus-derived biologic response
      modifier, OK-432, to augment NK lysis of uninfected K562 and U937 cells and HIV
      infected U937 cells by peripheral blood mononuclear cells (PBMC) from HIV
      seropositive homosexual men. Optimal two- to fourfold increases in lysis of the
      three targets were observed after pretreatment of PBMC from HIV-negative subjects
      for 4 h with 2 micrograms of OK-432 per ml. This effect was related primarily to
      gamma interferon (IFN-gamma) production induced by OK-432 and was not linked to
      production of tumor necrosis factors alpha and beta or to monocytes in the
      cultures. The enhancing effect of OK-432 on NK cell function was diminished but
      still evident in PBMC from subjects with relatively early-phase (< 3-year) HIV
      infection and high CD4+ cell counts and was lower in subjects with longer-term
      HIV infection (> 3 years), in association with reduced production of IFN-gamma.
      Augmentation of NK cell activity in HIV-infected men by OK-432 was comparable to
      that induced by treatment of cells with 1,000 U of IFN-alpha or interleukin 2 per
      ml. The data suggest that the NK cell-enhancing effects of OK-432 are at least in
      part mediated by IFN-gamma and that OK-432 may be effective in treatment of
      patients with early-phase HIV infection.

PMID- 7719920
TI  - An evaluation of the effectiveness of three immunoglobulin G (IgG) removal
      procedures for routine IgM serological testing.
AB  - Three procedures for the removal of immunoglobulin G (IgG) from human serum were
      evaluated for their effectiveness in eliminating false-positive results caused by
      rheumatoid factor and in removing IgG from serum to reduce competing-IgG
      interference in IgM enzyme-linked immunosorbent assay (ELISA) testing. The
      procedures investigated employed two anti-human IgG diluents and a recombinant
      protein G-filled tube. The anti-human IgG was more effective than the protein G
      method in eliminating false-positive results caused by rheumatoid factor and
      removed 5.4% more IgG from serum samples in the normal range (< 1,700 mg/dl) and
      up to 16.4% more of the IgG from samples with elevated levels (> 1,700 mg/dl).
      The recombinant protein G removed less IgM than the anti-human IgG diluents;
      however, this difference did not affect the results of the ELISA. For these
      reasons, the in-house-developed anti-human IgG diluent proved to be the most
      effective and economical for IgM serological testing.

PMID- 7719921
TI  - Characteristic features of the nucleotide sequences of yeast mitochondrial
      ribosomal protein genes as analyzed by computer program GeneMark.
AB  - The nucleotide sequence data for yeast mitochondrial ribosomal protein (MRP)
      genes were analyzed by the computer program GeneMark which predicts the presence
      of likely genes in sequence data by calculating statistical biases in the
      appearance of consecutive nucleotides. The program uses a set of standard
      sequence data for this calculation. We used this program for the analysis of
      yeast nucleotide sequence data containing MRP genes, hoping to obtain information
      as to whether they share features in common that are different from other yeast
      genes. Sequence data sets for ordinary yeast genes and for 27 known MRP genes
      were used. The MRP genes were nicely predicted as likely genes regardless of the
      data sets used, whereas other yeast genes were predicted to be likely genes only
      when the data set for ordinary yeast genes was used. The assembled sequence data
      for chromosomes II, III, VIII and XI as well as the segmented data for chromosome
      V were analyzed in a similar manner. In addition to the known MRP genes, eleven
      ORF's were predicted to be likely MRP genes. Thus, the method seems very powerful
      in analyzing genes of heterologous origins.

PMID- 7719922
TI  - Mapping of sequence-tagged sites in rice by single strand conformation
      polymorphism.
AB  - The conditions for efficient single-strand conformation polymorphism (SSCP)
      detection were examined for its application to mapping of DNA regions in the rice
      genome. Temperature for electrophoresis and glycerol concentrations in gel
      affected SSCP patterns significantly. The optimal detection conditions for SSCP
      also depends on the nucleotide sequences of fragments analyzed. Fragments over
      300 bp show complicated patterns depending on their nucleotide sequences and were
      not suitable for SSCP analysis. Seventy primer pairs were designed from the
      sequence data available to amplify DNA regions as sequence tagged sites (STSs),
      and 39 of these STSs were found to generate SSCP between japonica rice
      (Nipponbare) and indica rice (Kasalath) in at least one of the experimental
      conditions. The maps of DNA fragments amplified from 186 F2-plant DNAs with 17
      primer pairs were successfully determined. This direct mapping method of the
      amplified DNA fragments with PCR is simple and quite sensitive, and can be used
      to set markers in the gap regions of a genetic linkage map.

PMID- 7719923
TI  - An expression profile of active genes in human lung.
AB  - An expression profile of genes active in the human lung was obtained by
      collecting 797 partial sequences from a 3'-directed cDNA library. Three genes
      were found to produce mRNA each of which comprised more than 1% of total mRNA.
      These three have been identified as genes for pulmonary surfactant apoprotein
      (PSP-A), Clara cells 10-kDa secretory protein, and HLA-E heavy chain. In the
      remaining 745 clones, 221 were composed of 89 species that occurred recurrently,
      and 524 clones appeared only once. Because the 3'-directed cDNA library
      faithfully represents the mRNA population in the source tissue, these numbers
      represent the relative activities of the gene expression. Altogether 437 gene
      species were novel, and 179 gene species were identified in GenBank. A
      significant portion of these genes encode proteins found in secretory proteins,
      cell surface proteins, and components in the protein synthesis machinery,
      representing the function of the lung.

PMID- 7719924
TI  - A novel method for generating nested deletions using the in vitro bacteriophage
      T3 DNA packaging system.
AB  - To sequence a DNA segment inserted into a cosmid vector under the directed
      sequencing strategy, we established a simple and rapid method for generating
      nested deletions which uses the in vitro packaging system of bacteriophage T3
      DNA. The principle is based on the previous finding that this system can
      translocate any linear double-stranded DNA up to 40 kb into the phage capsid in a
      time-dependent manner and the encapsulated DNA becomes DNase-resistant. For this
      purpose, we constructed a cosmid vector that carries two different antibiotic
      selection markers at both sides of the multiple cloning site, and after insertion
      of a DNA segment, the clone was linearized by lambda-terminase at the cos site.
      After the packaging reaction in vitro followed by DNase treatment, the
      encapsulated DNA was introduced into Escherichia coli cells to give clones with
      unidirectional deletions by differential antibiotic selection. Restriction and
      sequence analyses of deletion clones demonstrated that an ordered set of clones
      with nested deletions, ranging from less than 1 kb to 25 kb, was created from
      either the end of the DNA segment. Thus, nested deletion clones that cover the
      entire region of a approximately 40-kb cosmid insert can be obtained by a single
      packaging reaction, and its restriction map can be simultaneously obtained.

PMID- 7719925
TI  - DNA sequencing using ultra small amounts of reagents and template.
AB  - One of the key points in the genome project is finding ways to reduce the running
      cost in DNA sequencing. One way is to use a highly-sensitive fluorescent DNA
      sequencer, where only trace amounts of template DNA and reagents are needed. An
      experimental protocol optimized for the trace amounts of DNA analysis was
      established by using the hybridization reaction rate coefficient of primers on
      template DNA, which was estimated to be 7.5 x 10(5) M-1sec-1 at 37 degrees C. One
      femtomole of template DNA with 0.001 unit of modified T7 DNA polymerase
      (Sequenase Ver. 2.0) and also 0.45 fmol of M13 template DNA with 0.01 unit of Taq
      DNA polymerase were enough to sequence DNA of up to 400 bases.

PMID- 7719926
TI  - A physical map of the genome of a unicellular cyanobacterium Synechocystis sp.
      strain PCC6803.
AB  - An accurate physical map of the genome of a cyanobacterium, Synechocystis sp.
      strain PCC6803, was constructed on the basis of restriction and linking clone
      analysis. The genome contained 6 recognition sites for AscI, 25 sites for MluI,
      and 31 sites for SplI, and the entire genome size was estimated to be 3.6 Mb.
      Sixteen genes or gene clusters, including those involved in the photosynthetic
      systems, were localized on the physical map of the genome by hybridization. In
      the course of the above analysis, two extra chromosomal units with approximate
      sizes of 110 kb and 125 kb were identified.

PMID- 7719927
TI  - The route of administration is a major determinant of the transduction efficiency
      of rat tissues by adenoviral recombinants.
AB  - One of the key factors that determines the efficacy of adenovirus-mediated gene
      therapy in genetic diseases, is the degree and extent of transduction of the
      target cells by adenovirus (AV)-recombinants carrying the therapeutic gene or
      cDNA. In this paper we provide experimental evidence which indicates that the
      route of administration of the AV-recombinants has a major influence on the
      transduction of various tissues in young rats. The heart, diaphragm, intercostal
      muscles and thymus show high transduction after intra-arterial (left cardiac
      ventricle) injection. By contrast, the liver shows a high transduction after
      intravenous injection. A substantial viremia develops within 2 h of gastric
      rectal, intraperitoneal and intracardiac administration of AV recombinants. The
      number of adenoviral DNA copies per nucleus of transduced cells ranged from one
      to three in most tissues. These numbers correlated well with the overall
      transduction efficiency of the tissue determined by reporter gene expression. The
      various factors that determine which route of administration favors a high
      transduction rate in a particular tissue can be analyzed and this can lead to an
      improved efficiency of gene therapy in targeting a particular tissue in a
      disease.

PMID- 7719928
TI  - Design of a genetic immunotoxin to eliminate toxin immunogenicity.
AB  - Host antibody response to toxin molecules is a major obstacle to the use of
      immunotoxins as efficacious agents in the treatment of human cancer and other
      diseases. In this study, a genetic form of immunotoxin has been designed which
      should eliminate toxin immunogenicity by replacing the toxin protein moiety with
      weakly immunogenic or nonimmunogenic plasmid DNA. A recombinant bifunctional
      fusion protein, which consists of a human antibody Fab targeting moiety [directed
      against gp120, the envelope glycoprotein of human immunodeficiency virus (HIV)-1]
      and a human DNA binding moiety (protamine), is used as a gene carrier. Toxin
      plasmid DNAs expressing the catalytic fragment of Pseudomonas exotoxin A (PEA)
      statically interact with the fusion proteins to form soluble protein-DNA
      complexes. The complexes are specifically transferred into HIV-1-infected cells
      by receptor-mediated endocytosis, resulting in selective killing of the target
      cells. These 'genetic immunotoxins' may have significant advantages over protein
      immunotoxins for the treatment of a variety of human diseases.

PMID- 7719929
TI  - Modulation of gene expression after replication-deficient, recombinant adenovirus
      mediated gene transfer by the product of a second adenovirus vector.
AB  - To regulate gene expression following adenovirus-mediated gene transfer, a
      strategy was devised utilizing co-infection with two separate adenovirus vectors
      designed such that the product of one vector modulated the promoter of the second
      vector. To evaluate this strategy, AdEGR1.TNF, an adenovirus expressing tumor
      necrosis factor-alpha (TNF) under the control of the early growth response 1
      (EGR1) promoter, was used to regulate a transcription unit in AdIL8.beta gal, an
      adenovirus vector in which the TNF sensitive interleukin-8 (IL-8) promoter drives
      the expression of beta-galactosidase (beta-gal). Following infection of HS24
      cells with AdIL8.beta gal, addition of TNF to the culture induced the expression
      of beta-gal. Infection of HS24 cells with AdEGR1.TNF resulted in a dose-dependent
      secretion of TNF. Little beta-gal was produced following co-infection of the
      cells with the control vector AdCMV.Null (expressing no specific gene) and
      AdIL8.beta gal. In contrast, co-infection with AdIL8.beta gal and AdEGR1.TNF
      demonstrated, for a given dose of AdIL8.beta gal, increasing amounts of beta-gal
      expression dependent on the dose of AdEGR1.TNF. This model suggests control of
      gene expression in adenovirus-mediated gene transfer can be regulated by
      utilizing a promoter-gene expression cassette in one vector that modulates the
      expression of a promoter-gene expression cassette in a second vector.

PMID- 7719930
TI  - Efficient in vivo transduction of the neonatal mouse liver with pseudotyped
      retroviral vectors.
AB  - Ideal methods for human gene therapy will eventually include direct gene transfer
      to defective tissues in a patient in vivo. Toward that goal, we have used high
      titer, pseudotyped retroviral vectors expressing genes for the Escherichia coli
      beta-galactosidase (lacZ) or hepatitis B virus surface antigen (HBsAg) to infect
      mouse liver by in vivo direct injection into the liver parenchyma. We have found
      that a single percutaneous injection of small volumes of vectors into the newborn
      mouse liver leads to transduction of at least 25-30% of the hepatocytes
      throughout the liver, as judged by in situ staining of liver sections for beta
      gal activity at 4 weeks after injection. We have demonstrated that stable levels
      of HBsAg were also detected in the circulation of injected mice up to 4 months
      after HBsAg-vector injection. We suggest that the high efficiency of in vivo
      transduction in the neonatal liver and subsequent stable transgene expression by
      high-titer pseudotyped retroviral vectors in the absence of an invasive partial
      hepatectomy may effectively be applied to gene therapy studies in a number of
      human liver disease [corrected].

PMID- 7719931
TI  - Recombinant retroviral vector interferes with the detection of amphotropic
      replication competent retrovirus in standard culture assays.
AB  - Many protocols for gene therapy employ recombinant retroviral vectors, which are
      replication-defective retroviruses engineered to serve as gene delivery vehicles.
      The use of retroviral vectors for human gene therapy requires careful screening
      of vector-producing cell lines and culture supernatants to ensure the absence of
      replication competent retrovirus (RCR) in clinical products. In this study we
      have examined several different culture assays routinely used to test for the
      presence of RCR. Results indicate that cocultivation of a vector-producing cell
      line with a permissive cell line can reproducibly detect a low level of
      contaminating RCR. RCR was detected less frequently in direct tests of cell-free
      culture supernatants from a contaminated vector-producing line. Further studies
      revealed that recombinant retroviral vector can interfere, to varying degrees,
      with the detection of low-level RCR in culture supernatants when a marker rescue
      assay, an extended mink S+L- assay or a PG-4 S+L- assay is used. Interference can
      be partially overcome by culturing the vector preparation with a permissive cell
      line for several days before testing on the indicator cell line. The interference
      phenomenon we have observed may also occur in other culture assays routinely used
      for the detection of RCR.

PMID- 7719932
TI  - Strain related variations in adenovirally mediated transgene expression from
      mouse hepatocytes in vivo: comparisons between immunocompetent and
      immunodeficient inbred strains.
AB  - High efficiency gene transfer and gene expression in hepatocytes in vivo can be
      achieved using recombinant adenoviral vectors. However, the persistence of gene
      expression in different experimental animal models has been variable. To
      determine if similar differences could be observed in a single species,
      persistence of gene expression was studied in inbred strains of mice using a
      recombinant adenoviral vector that expresses human alpha 1-antitrypsin. Marked
      variability in the persistence of gene expression ranging from several weeks
      (C3H/HeJ and Balb/c) to more than 3 months [C57Bl/6, B10.A(2R) and B10.BR] was
      observed when this vector was transduced in different strains of inbred mice.
      This variability did not correlate with H-2 type. To evaluate the role of T and B
      cell immunity in the persistence of gene expression, congenic C3H-scid and Balb/c
      scid mice were studied and found to have indefinite gene expression from
      transduced hepatocytes. These animals unlike their immunocompetent counter-parts
      were able to undergo secondary transduction of hepatocytes with a different
      recombinant adenoviral vector. These findings suggest that as yet unidentified
      genetic loci influence the persistence of adenovirus-mediated hepatic gene
      expression in vivo, and these effects are mediated at least in part, by the
      antigen specific immune system.

PMID- 7719933
TI  - Interleukin-2 gene therapy in a patient with glioblastoma.
AB  - A patient with glioblastoma multiforme (GBM) who had failed conventional therapy
      was treated with IL-2 gene therapy. The patient received 10 subcutaneous
      immunizations with autologous tumor cells and fibroblasts genetically modified to
      secrete IL-2 by retroviral gene transfer. An antitumor immune response mediated
      in part by CD8+ cytotoxic T cells was demonstrated with the patient's peripheral
      blood mononuclear cells. A magnetic resonance imaging (MRI) scan performed 4
      weeks after the highest treatment dose revealed marked tumor necrosis. These
      results support the evaluation of this form of IL-2 gene therapy in additional
      patients with glioblastoma.

PMID- 7719934
TI  - Gene therapy 1995: developments on the horizon.

PMID- 7719935
TI  - Antitumor effects of interleukin-12 (IL-12): applications for the immunotherapy
      and gene therapy of cancer.
AB  - Interleukin-12 (IL-12) is a pleiotropic cytokine, formerly termed cytotoxic
      lymphocyte maturation factor (CLMF) or natural killer cell stimulatory factor
      (NKSF), which is produced primarily by stimulated macrophages. IL-12 is a
      disulfide-linked heterodimeric cytokine composed of a 35-kDa light chain (p35)
      and a 40-kDa heavy chain (p40). Unlike most other cytokines, simultaneous
      transfection of mammalian cells with two different genes is necessary for the
      production of biologically active IL-12. IL-12 exerts a variety of biological
      effects on human T and natural killer (NK) cells in vitro, in addition to its
      ability to promote cytolytic activity, including direct stimulation of the
      production of IFN-gamma and other cytokines from peripheral blood T and NK cells.
      The recent finding that IL-12 directs the development of a TH1 type immune
      response from naive T cells demonstrates the critical role of IL-12 in regulating
      the immune response. The characteristics of IL-12 function described above
      strongly suggest its potential usefulness in cancer therapy. Indeed, our studies
      demonstrate that IL-12 exerts potent antitumor effects following systemic or
      local administration. We have shown that IL-12 delivered by retroviral vectors
      allows high-level expression and effective eradication of established tumor in
      multiple murine tumor models including MCA207 sarcoma. Successful therapy is
      associated with acquisition of a state of long-term, specific and protective
      immunity to subsequent challenge with tumor. We have recently received approval
      from the Recombinant DNA Advisory Committee to proceed with IL-12 gene therapy in
      humans.

PMID- 7719936
TI  - Combinatorial regulation of transcription. I: General aspects of transcriptional
      control.

PMID- 7719937
TI  - Identification and purification of human Stat proteins activated in response to
      interleukin-2.
AB  - A key cytokine induced during the immune response is IL-2. Following T cell
      activation, the genes encoding IL-2 and the various chains of its receptor are
      transcriptionally induced. In turn, secreted IL-2 serves to stimulate the
      proliferation and differentiation of T lymphocytes. Several recent studies have
      implicated Jak kinases in the signaling pathway induced by IL-2. Following this
      lead, we set out to identify transcription factors induced in response to IL-2.
      Human peripheral blood lymphocytes were observed to contain several IL-2
      inducible DNA binding activities. Similar activities were also observed in a
      transformed human lymphocyte line, termed YT. We have purified these activities
      and found that the principal IL-2-inducible component bears significant
      relatedness to a prolactin-induced transcription factor first identified in sheep
      mammary gland tissue. We hypothesize that activation of this protein, designated
      hStat5, helps govern the biological effects of IL-2 during the immune response.

PMID- 7719938
TI  - The role of shared receptor motifs and common Stat proteins in the generation of
      cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15.
AB  - To understand the molecular bases for cytokine redundancy and pleiotropy, we have
      compared the Stat proteins activated in peripheral blood lymphocytes (PBLs) by
      cytokines with shared and distinct actions. Interleukin-2 (IL-2) rapidly
      activated Stat5 in fresh PBL, and Stat3 and Stat5 in preactivated PBL. IL-7 and
      IL-15 induced the same complexes as IL-2, a feature explained by the existence of
      similar tyrosine-phosphorylated motifs in the cytoplasmic domains of IL-2R beta
      and IL-7R that can serve as docking sites for Stat proteins. IL-13 Induced the
      same complexes as IL-4, a finding explained by our studies implicating IL-4R as a
      shared component of the receptors. These studies demonstrate that a single
      cytokine can activate different combinations of Stat proteins under different
      physiological conditions, and also indicate two mechanisms by which distinct
      cytokines can activate the same Stat protein.

PMID- 7719939
TI  - A signaling pathway coupled to T cell receptor ligation by MMTV superantigen
      leading to transient activation and programmed cell death.
AB  - Stimulation of T cells by retroviral and bacterial super-antigens is followed by
      specific T cell elimination, in contrast with stimulation of T cells by peptide,
      which is usually associated with clonal expansion. We show here that this
      differential response phenotype is apparent at the level of individual T cell
      clones following TCR ligation with peptide or MTV antigen. We exploited selective
      coupling of apoptosis to TCR ligation by MTV7 to examine some of the
      intracellular biochemical events that underlie this response. MTV-dependent
      activation resulting in apoptosis was associated with activation of phospholipase
      A2 and the generation of reactive oxygen intermediates. Inhibition of these
      biochemical events prevented both MTV-dependent activation and apoptosis without
      affecting the peptide-dependent response of the same T cell clones. These results
      indicate that clonal expansion or programmed cell death following TCR ligation
      may be consequences of distinct TCR-coupled signaling pathways.

PMID- 7719940
TI  - Asymmetric processing of coding ends and the effect of coding end nucleotide
      composition on V(D)J recombination.
AB  - The products of V(D)J recombination are coding and signal joints. We show that
      the nucleotide composition of the coding ends affects V(D)J recombination. The
      presence of Ts at the 5' end of either the 12 mer or the 23 mer recombination
      signal sequence (RSS) greatly decreases coding and signal joint formation, and Ts
      at the 5' ends of both RSSs eliminate recombination, suggesting that a step
      during the initiation phase of the recombination is affected. A 5' T coding end
      can be rescued it the other end contains 5' G, C, or A, implying that synapsis
      may be required. Furthermore, the presence of As at the 5' end of the 12 mer, but
      not the 23 mer, RSS affects coding but not signal joint formation. This
      observation of asymmetric processing of coding ends suggests that different
      protein complexes are bound to the two RSSs, and become transferred to the
      aligned coding ends during processing.

PMID- 7719941
TI  - TCR alpha-CD3 delta epsilon association is the initial step in alpha beta dimer
      formation in murine T cells and is limiting in immature CD4+ CD8+ thymocytes.
AB  - The present study has examined the molecular events leading to formation of alpha
      beta dimers in normal murine thymocytes and mature T cells. We demonstrate that
      TCR assembly proceeds by initial association of TCR alpha with CD3 delta epsilon
      proteins and by association of TCR beta with CD3 gamma epsilon proteins to form
      alpha delta epsilon and beta gamma epsilon trimers; these trimers then associate
      to form alpha delta epsilon-beta gamma epsilon complexes, within which alpha-beta
      disulfide bond formation occurs. We also show that TCR-associated protein (TRAP)
      associates uniquely with CD3 gamma epsilon pairs and that formation of beta gamma
      epsilon trimers occurs subsequent to TRAP dissociation. Importantly, we document
      that the assembly step that is quantitatively limiting in CD4+ CD8+ thymocytes is
      the initial association of TCR alpha with CD3 delta epsilon chains, which appears
      necessary to protect nascent TCR alpha proteins from accelerated degradation
      within the ER of immature thymocytes.

PMID- 7719942
TI  - CD3 epsilon and CD3 zeta cytoplasmic domains can independently generate signals
      for T cell development and function.
AB  - To determine whether CD3 epsilon and CD3 zeta proteins have unique roles in TCR
      dependent functions, chimeric genes encoding the extracellular and transmembrane
      domains of the human IL-2 receptor alpha chain (Tac) fused to a cytoplasmic
      domain of either the CD3 epsilon or CD3 zeta chain were introduced as transgenes
      into both normal and RAG2-deficient (RAG2-/-) mice. Developmental arrest of T
      lineage cells at the CD4, CD8 double-negative stage in the transgenic RAG2-/-
      thymus was released to the CD4, CD8 double-positive (DP) stage by in vivo cross
      linking of TT epsilon or TT zeta with anti-Tac antibody. In TT epsilon + or TT
      zeta +, RAG2-/- mice, in vitro cross-linking of TT epsilon and TT zeta induced DP
      thymocyte cell death and proliferation of mature single-positive T cells.
      Overall, no qualitative differences were observed between TT epsilon- and TT zeta
      mediated functions, suggesting that different CD3 components deliver
      qualitatively similar signals in inducing TCR-dependent functions.

PMID- 7719943
TI  - Asymmetric signaling requirements for thymocyte commitment to the CD4+ versus
      CD8+ T cell lineages: a new perspective on thymic commitment and selection.
AB  - Differentiation of immature CD4+ CD8+ thymocytes into mature CD4+ CD8- and CD4
      CD8+ T cells requires that synthesis of one or the other coreceptor molecule be
      terminated, a process referred to as lineage commitment. The present study has
      utilized a novel coreceptor reexpression assay to identify lineage commitment in
      immature thymocytes and has found that the MHC recognition requirements for CD4
      commitment and CD8 commitment fundamentally differ from one another. Remarkably,
      we found that thymocyte commitment to the CD8+ lineage requires MHC class I
      dependent instructional signals, whereas thymocyte commitment to the CD4+ lineage
      is MHC independent and may occur by default. In addition, an unanticipated
      relationship between lineage commitment and surface phenotype has been
      identified. These results are incompatible with current concepts and require a
      new perspective on lineage commitment and positive selection, which we refer to
      as asymmetric commitment.

PMID- 7719944
TI  - Congestive heart failure: public and private burden.
AB  - Chronic congestive heart failure (CHF) is a common yet devastating syndrome. CHF
      is a leading cause of morbidity and mortality in the United States and other
      industrialized countries. The incidence and prevalence of CHF is increasing,
      placing a growing burden on the health care system. Patients suffering from CHF
      report a poor quality of life because of physical symptoms, functional
      disability, emotional and economic burdens, frequent hospitalizations, and poor
      prognosis. Nurses play a key role in the identification of strategies for
      effective management of CHF.

PMID- 7719945
TI  - Pathophysiology of heart failure: neuroendocrine response.
AB  - The understanding of the pathophysiology of heart failure is an emerging science.
      Although the mortality rate remains high, there has been some improvement in
      treatment in recent years. What was once thought to be a purely hemodynamic
      disorder now is understood to be a disease of cellular pathophysiology. The
      progression of compensated ventricular dysfunction to symptomatic heart failure
      is marked by the activation of vasoconstrictor hormones. Norepinephrine, renin
      angiotensin-aldosterone, and arginine vasopressin are secreted in response to
      inadequate systemic perfusion. These combine to increase preload and afterload on
      an already failing heart. Baroreceptor function is attenuated, allowing for the
      continued sympathoexecitatory state. In addition, local tissue factors mitigate
      against a return to normal ventricular function by down-regulation of beta
      receptors, stimulation of local vasoconstrictor hormone secretion, and promotion
      of growth. Patients in intensive care units with chronic heart failure are best
      managed with an understanding of how their altered physiology affects their
      clinical presentation.

PMID- 7719946
TI  - Pharmacologic management of congestive heart failure.
AB  - This article is a review of the pharmacologic management of congestive heart
      failure (CHF) and a summary of the medical literature that guides current
      treatment strategies. Despite advances in the treatment of CHF, it remains a
      common diagnosis with a poor prognosis. Because CHF is a progressive syndrome
      with heterogeneous features of cardiac dysfunction, effective management requires
      combination therapies and evolving treatment strategies. The mechanism of action,
      goals of therapy, and demonstrated efficacy of each of the various agents used in
      the treatment of CHF are discussed.

PMID- 7719947
TI  - Surgical therapy of chronic heart failure and severe ventricular dysfunction.
AB  - Even with multiple medical advancements, heart failure patients still have a
      dismal prognosis. Technologic improvements in coronary artery bypass graft (CABG)
      surgery have led to the use of high-risk myocardial revascularization for the
      treatment of patients with heart failure and severe ventricular dysfunction. This
      article describes advances in cardiac surgery and their impact on the treatment
      of heart failure. Postoperative management of the heart failure patient is also
      discussed. Because patient selection is important in achieving positive surgical
      outcomes, the role of prospective severity risk score is also addressed.

PMID- 7719948
TI  - Dynamic cardiomyoplasty.
AB  - Dynamic cardiomyoplasty, which uses transformed fatigue-resistant skeletal muscle
      to augment ventricular function, is an experimental surgical technique that shows
      promise as a treatment for patients suffering from heart failure. Successful
      management of this challenging patient population requires knowledge of (1)
      skeletal muscle physiology and management of muscle training, (2) details of the
      surgical procedure, and (3) patient management priorities.

PMID- 7719949
TI  - Bridge to cardiac transplantation: current practice.
AB  - Cardiac transplantation is primarily limited by the undersupply of donor organs.
      An estimated 20% of all heart transplant candidates will die before a donor heart
      becomes available. This high pretransplant mortality rate has prompted the
      institution of mechanical circulatory support (MCS) as a bridge to transplant for
      those who develop severe cardiac failure before cardiac transplantation.
      Actuarial survival in MCS patients after cardiac transplantation is equal to that
      of transplant recipients treated with more conventional therapies. These results
      have encouraged researchers in the field to investigate portable devices and more
      permanent implants. Current practice at one transplant center offers the Novacor
      (Baxter Healthcare), Thoratec (Thoratec Laboratories, Inc), and Cardiowest
      (Cardiowest Technologies, Inc) bridge-to-transplant devices. This article will
      discuss each device in detail. Other areas addressed include patient selection,
      patient management, and quality of life (QOL).

PMID- 7719950
TI  - The pathophysiologic process of ventricular remodeling: from infarct to failure.
AB  - In the past, hypertensive heart disease was the principal cause of congestive
      heart failure, but currently ischemic heart disease is the major etiologic
      factor. In the last 20 years, the role of myocardial infarction (MI) and the
      subsequent alteration in ventricular architecture of the infarcted and
      noninfarcted myocardium have become increasingly associated with a phenomenon
      known as ventricular remodelling. This process consists of left ventricular wall
      thinning in the infarction area, ventricular chamber dilatation, and compensatory
      hypertrophy of the noninfarcted portion of the myocardium. This article describes
      the pathophysiologic transformation that begins with MI and ventricular
      remodeling and ends in congestive heart failure.

PMID- 7719951
TI  - Critical care management of the heart failure patient in the home.
AB  - Deaths due to cardiovascular disease have decreased as the result of advances in
      medical therapeutics, advanced technology, and health promotion activities.
      Increased survival has resulted in a significant rise in the number of patients
      with chronic, refractory heart failure requiring intensive medical management and
      follow-up. Home care nurses trained in advanced cardiac assessment can decrease
      the cost of care by providing advanced technologic care in the home. Home
      dobutamine infusions are one example of provision of high-technology services in
      the home. With careful patient selection, adequate preparation, and home
      monitoring, dobutamine infusions can be provided in the home to improve the
      functional status and quality of life of patients with severe heart failure.

PMID- 7719952
TI  - Hypermobility features in patients with hand osteoarthritis.
AB  - In this study of 100 patients with established hand osteoarthritis (OA) and 100
      matched controls, clinical thumb base OA was more common in subjects with
      features of articular hypermobility. Hypermobile patients also had more severe
      thumb base involvement and more disability, but less interphalangeal joint OA.
      This trend was evident even in patients with moderate laxity (Beighton score > or
      = 2), and there was a significant correlation between disability and the number
      of hypermobility criteria. The majority of patients who had their initial
      symptoms from the first carpometacarpal joint, and those who had severe OA in
      that joint, had hypermobility features. This study indicates a relationship
      between hypermobility and the development of thumb base OA, and suggests that
      'hypermobility-associated OA' may be a hitherto unrecognized subset of hand OA.

PMID- 7719953
TI  - Topographical variation within the articular cartilage and subchondral bone of
      the normal ovine knee joint: a histological approach.
AB  - Topographical variation in the articular cartilage and subchondral bone of the
      normal ovine knee was examined using histological techniques. The articular
      cartilage was examined grossly, then histological sections were cut and the
      cartilage thickness and chondrocyte density were measured. Bone mineral density,
      thickness of the subchondral bone plate (SBP) and volume and surface
      histomorphometrical parameters and mineral apposition rate were calculated for
      the subchondral bone. It was found that the articular cartilage on the tibial
      plateaux was thicker, less cellular, and overlay a thicker SBP than that on the
      femoral condyles. Similarly, the cartilage in the medial joint compartments was
      thicker, less cellular and overlying a thicker less dense SBP than that in the
      lateral joint compartments. There was no variation in bone histomorphometric
      parameters or mineral apposition rate between regions. Biomechanical testing has
      shown that loading is not uniform throughout the normal human knee joint. The
      present results suggest that loading within the ovine knee is also nonuniform,
      with the central regions of the tibial plateaux bearing greater loads than the
      femoral condyles, and the medial joint compartment being loaded more than the
      lateral one. The articular cartilage and subchondral bone have adapted in order
      to best withstand these variations in loading. These histological findings, plus
      the topographical variations in cartilage biochemistry reported by Read et al.
      (Topographical variation in composition, PG-biosynthesis and swelling pressure of
      cartilages of loaded tibio-femoral joints (Abstract). Proceedings of the Combined
      Meeting of the Orthopaedic Research Societies of USA, Japan and Canada.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7719954
TI  - Calcium pyrophosphate dihydrate crystal deposition disease: a review of the
      literature and a light and electron microscopic study of a case of the
      temporomandibular joint with numerous intracellular crystals in the chondrocytes.
AB  - The pathogenesis of calcium pyrophosphate dihydrate (CPPD) crystal deposition
      disease of synovial joints is still unclear, although overproduction of
      extracellular pyrophosphate (PPi) is thought to play a key role. We studied the
      light and electron microscopic appearances of a case of CPPD crystal deposition
      disease of the temporomandibular joint (TMJ) in search of new clues for its
      pathogenesis. Light microscopic examination of CPPD-containing material from the
      joint space revealed cartilaginous nodules with various degrees of
      crystallization. Transmission electron microscopic examination revealed numerous
      extra- as well as intracellular crystals and crystal shaped spaces in the
      chondrocytes. Other striking ultrastructural features of the chondrocytes
      included the presence of many mitochondria, frequently containing crystalline
      material, and the presence of highly dilated rough endoplasmic reticulum and
      large glycogen islands. The presence of intramitochondrial crystals may
      hypothetically imply a derangement in mitochondrial adenosine triphosphate or PPi
      metabolism. The finding of intracellular CPPD crystals in chondrocytes points to
      the existence of an intracellular pathway of CPPD crystal formation in CPPD
      crystal deposition disease of the TMJ and possibly in CPPD crystal deposition
      disease in general.

PMID- 7719955
TI  - Local and remote matrix responses to chondrocyte-laden collagen scaffold
      implantation in extensive articular cartilage defects.
AB  - Chondrocyte-laden collagen scaffolds were evaluated in extensive cartilage
      defects in an equine model. Arthroscopic techniques were used to implant a
      chondrocyte-collagen culture product in 15-mm defects in the lateral trochlear
      ridge of the femoropatellar joint of 12 horses. Ungrafted control defects were
      formed in the opposite joint. Groups of six horses were terminated at 4 and 8
      months after implantation and the repair sites, adjacent cartilage, and remote
      cartilage within each femoropatellar joint examined biochemically. Eight months
      following surgery the relative proportions of type II collagen in grafted and
      ungrafted defects, determined using the ratio of cyanogen bromide cleavage
      products alpha 1(II)CB10/alpha 2(I)CB3,5, were not significantly different (31.57
      +/- 2.76% and 26.88 +/- 2.76%, respectively). Aggrecan content was significantly
      improved in grafted defects (85.61 +/- 6.51 and 74.91 +/- 10.31 micrograms/mg dry
      weight). Cartilage surrounding grafted defects also showed improved maintenance
      of cartilage glycosaminoglycan content. Thus, chondrocyte grafting in collagen
      scaffold vehicles improved the aggrecan content in extensive cartilage defects
      and surrounding normal cartilage. However, given the continued disparity between
      repair tissue and normal cartilage aggrecan content, and the low proportion of
      type II collagen in grafted defects, the utility of collagen scaffolds for
      chondrocyte grafting of large cartilage defects seems limited.

PMID- 7719957
TI  - Effects of testosterone on triglyceride uptake and mobilization in different
      adipose tissues in male rats in vivo.
AB  - The effects of testosterone (T) on uptake and mobilization of orally administered
      triglyceride were examined in male rats. In order to attempt to explain regional
      differences, adipose tissue metabolism was studied in vivo. (U-14 C) oleic acid
      in sesame oil was given by gastric gavage to male, sham operated, castrated and
      castrated + T substituted rats, and accumulation and half-life of radioactivity
      measured. In castrated rats in comparisons with sham-operated and castrated + T
      rats, serum T was absent, and body weight lower (p < 0.05 or 0.01), but
      adipocytes in retroperitoneal and mesenteric tissues became significantly
      heavier. Radioactivity (dpm/mg triglyceride) was higher, in retroperitoneal
      tissue at 4 hours, 7, 30 days, and in mesenteric tissue at 4 hours, and at 30 and
      60 days after oral label administration (0.1 > p > 0.05 or p < 0.05), no
      differences were seen in epididymal or inguinal depots at 4 hours. When
      radioactivity was expressed per adipocyte, the castrated group showed
      significantly higher radioactivity when compared to sham and castrated + T groups
      at 7 and 30 days in retroperitoneal and at 60 days in mesenteric adipocytes (p <
      0.05 or 0.01). Half life (T 1/2) of radioactivity was longer in mesenteric tissue
      in the castrated rats than the other two groups (sham group, 33 days +/- 2;
      castrated group, 58 days +/- 6; and castrated + T group, 39 days +/- 3, p <
      0.05), but there were no differences between groups in retroperitoneal adipose
      tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7719956
TI  - Markers of cartilage matrix metabolism in human joint fluid and serum: the effect
      of exercise.
AB  - The concentrations of cartilage proteoglycan (aggrecan), stromelysin-1, tissue
      inhibitor of metalloproteinases-1 (TIMP-1) and procollagen II C-propeptide in
      knee joint fluid and the levels of aggrecan, hyaluronan and keratan sulfate in
      serum were measured before and after exercise in 33 healthy athletes. The samples
      before exercise were obtained after 24 h rest from running or soccer and the
      samples after exercise were obtained 30-60 min after the exercise. Nine athletes
      ran on a treadmill for 60 min, 16 ran on road for 80 min and 8 played one soccer
      game (90 min). A reference group of 28 patients with knee pain but not evidence
      of joint pathology or injury was used for comparison. In joint fluid no single
      marker from the degradative processes in cartilage matrix changed significantly
      with exercise but all showed a rising trend. All markers except stromelysin
      showed lower concentrations in athletes at rest compared to the reference group.
      In serum from runners before exercise the concentration of keratan sulfate was
      significantly higher than in both the soccer and reference groups and further
      increased after exercise. The increase in markers after exercise may reflect an
      effect of mechanical loading in combination with a possible high turnover rate of
      body cartilage matrix in these individuals.

PMID- 7719958
TI  - Pregnancy weight retention in morbid obesity.
AB  - Recent hypotheses suggest that for women who develop morbid obesity, increases in
      weight associated with pregnancy may represent a significant contribution to
      their obesity status. The effects of multiple pregnancies on weight gain were
      studied in 96 morbidly obese women (< 13.6 kg over ideal weight at ages 20-24 or
      before an earlier first pregnancy and currently > 44.5 kg over ideal weight) and
      115 random control women from the Utah population. Self-reported weights for each
      pregnancy included: prepregnancy, greatest during pregnancy, and 6 weeks
      following delivery, which were validated against available hospital records. Mean
      number of pregnancies in each group were similar (4.2 and 4.3), ranging from 1 to
      9. Mean current age was 46 and mean weight gain since ages 20-24 was 46.0 kg in
      the morbidly obese and 14.1 kg in controls. Regression of current weight on total
      number of pregnancies, adjusting for weight at ages 20-24, showed a 1.3
      kg/pregnancy increase in current weight (p = 0.03) with no difference between
      groups (p = 0.6). Weight gain subsequent to the last pregnancy was not related to
      the number of pregnancies (p = 0.2). Morbidly obese women gained more weight
      during pregnancy than controls only for the first pregnancy. Gains were similar
      for all other pregnancies. Morbidly obese women had smaller weight losses after
      delivery than the controls, but these differences were not significant. For the
      first pregnancy, morbidly obese women had a net weight retention that was 4.0 kg
      greater than the controls at 6 weeks post-partum and an average of 1.6
      kg/pregnancy greater retention for the remaining pregnancies. Pregnancy weight
      gains for each pregnancy subsequent to the first pregnancy were constant. These
      findings suggest: 1) women who develop morbid obesity have slightly less weight
      loss after delivery and greater between-pregnancy weight gains than controls; 2)
      the number of pregnancies does not affect the amount of weight gained after the
      last pregnancy; and 3) while multiparity may augment weight gain in morbidly
      obese women, it is probably not a primary factor in the later development of
      morbid obesity.

PMID- 7719959
TI  - Both maternal over- and undernutrition during gestation increase the adiposity of
      young adult progeny in rats.
AB  - We examined the influence of maternal diet during gestation on the growth and
      body composition of the progeny. On day 1 of gestation, rat dams were assigned to
      one of four feeding regimens: free access to standard rodent chow throughout
      gestation (AL); 20 g feed/day (prebreeding intake) throughout gestation (PB); 10
      g feed/day from day 1 to day 14, then ad libitum from day 15 to parturition
      (RAL); 10 g feed/day from day 1 to 14, then 20 g/day to parturition (RPB).
      Progeny were fed ad libitum on standard chow diet from 3 to 12 weeks of age; food
      intake and weight gain were measured over this time. Body composition was
      measured at 12 weeks. The PB regimen restricted maternal food intake during the
      third trimester only; the RAL regimen restricted intake by 50% for two trimesters
      and produced hyperphagia in the third; the RPB regimen restricted intake by 50%
      for two trimesters, then intake (per unit body weight) was similar to that of AL
      dams during the third trimester. Litter size and progeny birth, weaning, and 12
      week body weights were similar among the four groups. At 12 weeks of age, PB
      progeny had the highest body fat (per kg fat-free mass), despite similar feed
      intake during the 9-week postweaning period. The increased fat was proportionally
      distributed among intra-abdominal and subcutaneous depots. Progeny of RAL, AL,
      and RPB dams had similar amounts of body fat, but in RAL progeny more fat was
      present in intra-abdominal depots. The weights of fat-free mass, gastrointestinal
      tract and hindlimb skeletal muscles were unaffected by maternal diet. Restriction
      of maternal feed intake during the third week of gestation had subtle effects on
      the body composition of young adult progeny that could not be explained on the
      basis of differences in postweaning voluntary feed intake.

PMID- 7719960
TI  - Relation of body fat distribution to reproductive factors in pre- and
      postmenopausal women.
AB  - The cross-sectional relations of several reproductive characteristics with self
      reported waist-to-hip circumference ratio were evaluated in 44,487 pre- and
      postmenopausal women 40 to 65 years of age who were free of cancer,
      cardiovascular disease, and diabetes. All results were adjusted for age, body
      mass index, cigarette smoking, physical activity, and alcohol intake. Current use
      of postmenopausal hormones was associated with a significantly lower waist-to-hip
      ratio than either past or never use independent of type of menopause (0.778
      versus 0.784, p = 0.0001 and 0.787, p = 0.0001, respectively), although
      associations with type (unopposed estrogens versus combined estrogen and
      progesterone) and duration of hormone therapy were not noted. Waist-to-hip ratio
      did not differ between pre- and postmenopausal women, but demonstrated weak
      positive associations with age at menarche, parity, and age at first birth, and a
      weak inverse association with past duration of breast-feeding. These data confirm
      relations of several reproductive factors and use of hormone replacement therapy
      with body fat distribution. Epidemiologic studies relating body fat distribution
      to disease outcomes in women should consider these factors as potential
      confounders.

PMID- 7719961
TI  - The association of body weight, dietary intake, and energy expenditure with
      dietary restraint and disinhibition.
AB  - The hypotheses that dieting and/or overeating are associated with adiposity,
      eating disturbances, and lowered energy expenditure were tested in this study. A
      sample of 44 premenopausal women scoring high and low on measures of dietary
      restraint and disinhibition of dietary control, as measured by the Three Factor
      Eating Questionnaire, was studied. A 2 x 2 factorial design was employed
      (High/Low restraint x High/Low Disinhibition). Dependent variables were: body
      composition, dietary intake, activity, resting metabolic rate, and thermic effect
      of food. Unrestrained overeaters (Low Restraint/High Disinhibition group) were
      very obese. High Dietary Restraint was associated with intent to diet and
      controlled eating. High scores on the Disinhibition Scale were associated with
      episodic overeating. Groups did not differ in resting metabolic rate (controlled
      for fat-free mass). Lower thermic effect of food was found to be associated with
      the obesity found in High Disinhibition subjects. Thus, Dietary Restraint was not
      associated with significant adverse effects upon physical or psychological
      health. High Disinhibition, however, was associated with adiposity and
      significant disturbances of eating.

PMID- 7719962
TI  - History of intentional and unintentional weight loss in a population-based sample
      of women aged 55 to 69 years.
AB  - Although both overweight and body weight fluctuation are related to chronic
      disease risk, little is known about the history of and reasons for body weight
      change in the general population. This paper reports the incidence of intentional
      and unintentional weight loss episodes during adulthood in a population-based
      sample of 26,261 women aged 55 to 69 years. Intentional weight loss episodes of
      each of four amounts (5-9, 10-19, 20-49, 50+ lbs.) and unintentional weight loss
      episodes of 20 or more lbs. were recalled for each of three age periods (18-39,
      40-54, 55+ years). At least one intentional weight loss episode of 5 or more lbs.
      was reported by 69% of women, 46% reported at least one intentional weight loss
      episode of 10 or more lbs, and 25% reported at least one intentional weight loss
      episode 20 or more lbs. At least one unintentional weight loss episode of 20 or
      more lbs. was reported by 29% of the women. Reasons for weight losses of 20 or
      more lbs. were also recalled. Women who had intentionally lost 20 or more lbs.
      were more likely to report weight losses due to low-calorie diets, exercise and
      weight loss groups, while women who had unintentionally lost 20 or more lbs. were
      more likely to report weight losses due to depression or stress. These findings
      question the common assumption that weight losses in adult women are primarily
      intentional and emphasize the need to distinguish the reasons for weight loss in
      studies examining the relationship between body weight changes and health
      outcomes.

PMID- 7719963
TI  - Identification of biochemical defects in pancreatic islets of fa/fa rats: a
      developmental study.
AB  - Adult obese (fa/fa) Zucker rats hypersecrete insulin in response to glucose and
      other secretagogues. Functional changes in islet alpha 2-adrenoceptors (8) and
      glycolytic regulation (9) have been reported. In this study, the development of
      these biochemical lesions in islets isolated from suckling (3 week old) and
      weanling (5 week old) lean and fa/fa rats was investigated and compared to
      results in adult animals. Glucose (15 mM)-induced insulin secretion was inhibited
      by mannoheptulose (MH) in lean (n = 8) but not fa/fa (n = 10) adult rats,
      indicating loss of sensitivity of glucokinase to competitive inhibition.
      Sensitivity to MH was somewhat reduced in the islets of 3- and 5-week-old fa/fa
      (n = 7 and 12) compared to lean (n = 15 and 9) rats, requiring 30-100 fold higher
      concentrations to achieve significant inhibition. At 3 weeks of age fa/fa rats
      did not differ from lean controls in either islet insulin content or body weight,
      but both parameters were increased in fa/fa rats by 5 weeks. The presence of
      altered alpha 2-adrenoceptor function in fa/fa rats could not be confirmed in
      this study. Unlike the previous report, prazosin did not antagonize alpha 2
      agonist mediated inhibition of insulin secretion. The presence of defective
      regulation of the glycolytic pathway by mannoheptulose in suckling and weanling
      rats may contribute to development of hyperinsulinemia in fa/fa rats.

PMID- 7719964
TI  - Dietary fat is shunted away from oxidation, toward storage in obese Zucker rats.
AB  - Previous measurements of lipoprotein lipase (LPL) activity in adipose tissue
      (ATLPL) of lean and obese Zucker rats have consistently documented increased
      activity in obese rats relative to lean. Since LPL is considered to be rate
      limiting for the delivery of triglyceride fatty acids (TGFA) to muscle and
      adipose tissue, these data have been used to suggest that the metabolic
      partitioning of TGFA favors storage over oxidation in obese rats. To document the
      partitioning of TGFA directly, the fate of 14C labeled oleic acid (42nmols) was
      fed to lean, obese, and obese Zucker rats fed a hypocaloric diet designed to
      chronically reduce weight 25% below that of obese controls (reduced-obese). The
      amount of 14C recovered in CO2 over 6 hours following ingestion was significantly
      less in obese rats compared to lean (0.45 +/- 0.06 vs. 0.88 +/- 0.09nmols, p =
      .0004) and less still in the reduced obese group (0.34 +/- 0.06nmols p = .00003).
      Six hours after ingestion, the quantity of label found in adipose tissue was
      significantly greater in the obese rats compared to lean (14.51 +/- 1.92 vs. 1.38
      +/- 0.29nmols p < .00001), but was intermediate in the reduced-obese group (9.23
      +/- 0.98nmols p = .0003). At 2.2 hours there was significantly more label in
      skeletal muscle of lean rats compared to either obese or reduced-obese (2.33 +/-
      0.24; 1.35 +/- 0.04nmols p = .01; 1.41 +/- 0.27nm p = .02). However, at 6 hours
      these differences between groups were no longer present. These finding Indicate
      that dietary fat is shunted away from oxidation toward storage in obese Zucker
      rats. Additionally it appears that there may be a relative block in the oxidation
      of TGFA that is taken up by skeletal muscle in obese rats. Finally the relative
      normalization of this partitioning defect in reduced-obese rats is at variance
      with what was suggested by previous measurements of tissue specific levels of
      LPL, and suggests an enhanced recirculation of fatty acids from adipose tissue to
      muscle in reduced-obese rats. This could occur through increased delivery of non
      esterified fatty acids (NEFA) to muscle as a result of an increase in net
      lipolysis.

PMID- 7719966
TI  - Response to Roback et al.

PMID- 7719965
TI  - Trafficking of dietary fat in lean rats.
AB  - Despite increasing interest in the role that fuel partitioning plays in
      determining body composition, the relative importance of oxidative versus storage
      pathways in the clearance of dietary fat remains unclear. A widely held view is
      that the primary destination of chylomicron triglyceride fatty acids (TGFA) is
      adipose tissue, and the primary source of lipid fuel for skeletal muscle is non
      esterified fatty acids (NEFA). An alternate view is that muscle, not adipose
      tissue, is the primary site of TGFA clearance. This view is supported by
      estimates of the total lipoprotein lipase content of muscle and adipose tissue.
      To directly study the partitioning of dietary fat between oxidation and storage,
      14C-labeled oleic acid was fed to Sprague Dawley rats and its metabolic rate
      followed over 30 days. Two hours after ingestion, more than 3.5 times as much
      label was found in skeletal muscle tissue (2.42 +/- 0.45 nmols) and CO2 (0.25 +/-
      0.01 nmols) than was found in adipose tissue (0.71 +/- 0.14 nmols). Intramuscular
      triglyceride was the lipid class most extensively labeled. After skeletal muscle,
      liver was the next most important site of TGFA clearance. Surprisingly a
      substantial quantity of label remained associated with the GI tract even 24 hours
      after ingestion. Between 2 and 10 days following ingestion there was a net
      decline in the 14C content of muscle, liver and GI tract, associated with a net
      rise in the 14C content of adipose tissue. These findings demonstrate: 1) the
      importance of skeletal muscle and liver in whole organism TGFA clearance, 2) the
      importance of intramuscular partitioning of lipid fuels between direct oxidation
      and storage as TG, 3) the potentially important role of the GI tract in the
      delivery of dietary fat to the circulation 10-24 hours following ingestion, and
      4) the stability of adipose tissue as a storage site. The complex nature of the
      tissue-specific clearance of TGFA over time is perhaps better described by the
      term "trafficking" than by the more commonly used term "partitioning." Future
      studies of TGFA clearance combined with sampling of relevant tissues over time
      will provide insight into the specific roles that abnormalities in liver, muscle
      and adipose tissue TGFA metabolism play in the development of
      hypertriglyceridemic disorders and states of increased or reduced body weight.

PMID- 7719967
TI  - From very-low-energy diets to fasting and back.

PMID- 7719968
TI  - A departure from the usual methods in treating obesity. 1929.

PMID- 7719969
TI  - New political climate ups need for nurse activism.

PMID- 7719970
TI  - PPCs revitalize to fight restructuring.

PMID- 7719971
TI  - Restructuring in CNA facilities: a roundup.

PMID- 7719972
TI  - National Institute on Aging/National Institute of Dental Research Workshop on
      Human Models of Skeletal Aging. Washington, D.C., March 1-2, 1994. Proceedings.

PMID- 7719994
TI  - [Advances in cosmetic surgery (1979-1994)].

PMID- 7719995
TI  - [Effect of WS-frequence spectrum physiatrics apparatus on survival of the random
      flap in rats].
AB  - In this experimental study we investigated the effect of WS-frequence spectrum
      physiatrics apparatus on the survival of the random flap in the back of rats. The
      flap was radiated vertically with the WS-apparatus for 30 minutes, twice daily
      for 8 days. It was found that on the ninth postoperative day, the survival areas
      of the radiated flaps was increased significantly (P < 0.001). The isotope
      (99mTc) clearance, the diaphanousflap sample and SOD content were examined. The
      results showed that WS-apparatus can reduce the production of oxygen free radicle
      in the flap, increase the tolerance for ischemia and blood supply of the flap
      with the proliferation and vasodilation of capillary vessels.

PMID- 7719996
TI  - [Clinical application of neurovascular island flap in the hand].
AB  - From 1962 to 1992, four kinds of neurovascular island flaps of the hand were used
      for the treatment of skin defects in the hand in 72 cases. Of these flaps, 38
      were pulp flaps of the finger, 24 were based on the first dorsal metacarpal
      artery, 7 were from second dorsal metacarpal artery and 3 were from hypothenar
      area. All the flaps survived except 1. Postoperative follow-up showed excellent
      or good results in 94.4%. The indications of the operation, flap design and
      surgical procedure are described. The anatomical feature, the advantages and
      disadvantages of the flap are discussed.

PMID- 7719997
TI  - [Clinical application of nasolabial subcutaneous pedicle skin flap with
      infraorbital artery].
AB  - The nasolabial subcutaneous pedicle skin flap with infraorbital artery has been
      successfully used in 5 cases when the angular artery and facial artery could not
      be used because of damage. The flap is a good option for small defect in nose and
      facial region.

PMID- 7719998
TI  - [Reconstruction of joint deformities of the extremities using random thin skin
      flap].

PMID- 7719999
TI  - [17-year retrospect of craniofacial surgery and its prospect].

PMID- 7720000
TI  - [Correction of ectropion of lower eyelid after plastic surgery for eyelid pouch].

PMID- 7720001
TI  - [The significance of fascial tissue of the upper eyelid in double eyelidplasty].
AB  - The anatomical structure of fascial tissue of the upper eyelid is described in
      this article. It is emphasized that removing redundant fascial tissue is an
      important procedure in the double-eyelid operation of the upper eyelid. This is
      especially true for patients with baggy deformities or blepharochalasis. Based on
      this principle, 654 cases of double eyelidplasty were performed from 1990 to 1993
      with satisfactory results revealed by postoperative follow-up of 1 month to 3
      years.

PMID- 7720002
TI  - [Experimental study on adipocyte culture in vitro].
AB  - The adipocyte belongs to a kind of end cells. Most people take a skeptical
      attitude to its ability of proliferation in vitro. Based on foreign scientists'
      experience in this aspect. We isolated rats' adipocytes with percoll-density
      gradient procedure. Using compound medium of DMEM and F12 with glucocorticoid,
      insulin and basic fibroblast growth factor (bFGF), we have succeeded in culturing
      fat cells in vitro.

PMID- 7720003
TI  - [Immunoelectronmicroscopic study of fibronectin in Kupffer's cell in rats with
      multiple organ failure].
AB  - This essay studied the content and distribution of Fibronectin (Fn) in Kupffer's
      cells in rats with multiple organ failure (MOF) with the immunoelectronmicroscopy
      technique. The results revealed that there was a significant increase in Fn level
      in plasma and the amount of immunogold particles in Kupffer's cells during the
      early stage, but the changes were not evident in the late stage. Our findings
      indicated that the changes in content of Fn was closely related to the function
      of MPS and might play an important role in the pathogenic mechanism of MOF.

PMID- 7720004
TI  - [Effects of delayed fluid resuscitation on dynamic properties of erythrocyte
      membrane protein after burn shock].
AB  - The dynamic properties of membrane protein are closely correlated to the membrane
      functions in erythrocytes. The anion transport function of band 3 protein, the
      constituents and the translational diffusion of membrane protein was detected in
      25% TBSA burn rats. The changes in membrane protein SH were investigated by using
      the spin label of 3-maleimide-proxyl. The results showed that, in delayed fluid
      resuscitation group after burn shock, membrane crosslinking protein appeared in
      erythrocytes, the function of band 3 protein was damaged, the recovery time after
      fluorescence photobleaching of membrane protein was obviously prolonged, and the
      ratio of peak heights of strong to weak immobilization was increased, especially
      in the six-hour delayed resuscitation group, suggesting that the ischemia
      reperfusion injury was more serious during the early shock stage. The authors
      believe that the results may represent the mechanism of damage biological
      membrane after burns. The alterations of membrane properties caused by free
      radicals play an important role in erythrocyte injury.

PMID- 7720005
TI  - [Endothelial cell injury and changes in anti-coagulation properties induced by
      burn serum in vitro].
AB  - The purpose of this study is to clarify the effect of burn rabbit serum on the
      function and structure of endothelial cells in vitro. Morphological study
      (inverted microscopy, scanning electron microscopy), and determinations of LDH, 6
      keto-PGF1 alpha and tissue-type plasminogen activator in the culture medium,
      changes in the ability of anti-adhesion of platelet to endothelial cells and anti
      aggregation property of platelet, etc. were performed. The main results and
      conclusions were as follows: (1) Rabbit serum obtained in the early stage exerted
      obvious toxic effects on endothelial cells, functional changes appeared earlier
      than structural, and in the later changes in intercellular junction and cellular
      surface appeared earlier; (2) Burn rabbit serum significantly reduced the ability
      of anti-adhesion of platelet to endothelial cell and anti-aggregation property of
      platelet, and it might be the primary cause of local micro-thrombosis; (3)
      Because of the destruction of endothelial surface, the ability of fibrinolysis of
      endothelial cells was reduced. The activity of tPA might be inhibited b PAI-1,
      although the content of tPA in the culture medium seemed to be increased after
      endothelial cell injury.

PMID- 7720006
TI  - [Prophylactic effect of systemic ceftazidime on bacterial translocation in
      scalded rats].
AB  - In this study, we evaluated the prophylactic effect of Ceftazidime on bacterial
      translocation (BT) of Pseudomonas aeruginosa in scalded rat by qualitative and
      quantitative bacterial cultures of blood, organs and mesenteric lymph nodes
      (MLN). Ceftazidi-me was administered systemically at 3 h, 6 h and 12 h post
      injury respectively. The dynamic changes in levels of Ceftazidime in blood and
      organ tissues were also determined. The results showed that effective levels of
      Ceftazidime in blood, liver and mucosa of the small intestine were rapidly
      reached and maintained for more than 4 h, but no drug was found in MLN. The
      prophylactic effect on BT was significant when systemic administration started at
      3 h post injury (P < 0.001) and 6 h post injury (P < 0.05). Although the
      incidence of BT was unchanged (P > 0.05) when systemic administration started at
      12 h, the number of organisms present in livers and kidneys, except MLN, was
      dramatically reduced (P < 0.01).

PMID- 7720007
TI  - [The effects of severe scald on the Leydig cells of testes in rats].
AB  - The changes in Leydig cells of testes were studied in rats inflicted with 30%
      third degree scald. Light and electron microscopy, enzyme histochemistry of 3
      beta-hydroxy steroid dehydrogenase (3 beta-HSD) determination of the relative
      activity of 3 beta-HSD, and assay of serum testosterone and luteinizing hormone
      (LH) were dynamically made for 30 days. It was found that there was various
      degree of degeneration and necrosis of Leydig cells. The activity of 3 beta-HSD
      in Leydig cells was rapidly reduced and remained at a relatively low level on the
      30th day after scald. The serum level of testosterone was decreased rapidly and
      remained at a comparatively low level on the 30th day after scald. No significant
      changes in serum luteinizing hormone were observed. The results suggest that
      decreased in serum testosterone after scald might be the result of damage of the
      Leydig cells and increase in glucocorticoids.

PMID- 7720008
TI  - [Mechanism of changes in coagulation after electric burns in rabbits].
AB  - The changes in local lesion after high-voltage electric burns ares dependent on
      many factors. One of the important factors is the change in coagulation. In this
      paper, a high-voltage electrical burn model was reproduced in rabbits for the
      purpose of investigating the coagulation mechanism. It was found that AT-III and
      PC showed elevation and declination, respectively, at 6h and 12h postburn. PAI:A
      and t-PA:A also showed obvious changes, while FDP showed continuous elevation at
      6h up to 5d postburn. The findings probable provided the explanation of the
      occurrence of thrombosis at 6h to 12h postburn, and the second episode of
      thrombosis on the 5th day.

PMID- 7720009
TI  - [Anatomy of the eyebrow and upper eyelid region and its significance in ptosis
      surgery].
AB  - The article reports the results of the anatomic observations from dissecting 30
      upper eyelids and 8 eyebrows of adult cadavers. In the eyebrow region, the
      anterior and posterior sheaths of the galea enclose the muscle plane where the
      frontalis, orbicularis and corrugator muscles are interdigitated. The posterior
      sheath attaches to supraorbital ridge through the brow fat pad. It was found that
      a few fibers of the frontalis muscle insert to the skin of the brow. In the upper
      eyelid, the orbital septum fuses with the aponeurosis at or just below the upper
      margin of the tarsus. The levator aponeurosis, Muller's muscle, particularly
      their attachments were carefully observed and measured. Finally, the application
      of the anatomy in the ptosis surgery is discussed.

PMID- 7720010
TI  - [Basic study of injectable collagen and its use in facial plastic surgery].

PMID- 7720011
TI  - Antimicrobial mode of action of secretions from the metapleural gland of Myrmecia
      gulosa (Australian bull ant).
AB  - Secretions from exocrine metapleural glands of Myrmecia gulosa (Australian bull
      ant) exhibit broad-spectrum antimicrobial activity. Treatment of the yeast
      Candida albicans with metapleural secretion resulted in the rapid and total
      leakage of K+ ions from cells within 10 min. Ultrastructural analysis of the
      bacteria Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa, and cells
      and protoplasts of Candida albicans demonstrated gross damage of the cell
      membrane and aggregation of the cytoplasmic matrix of treated cells. Degradation
      of membrane-bound organelles was also observed in Candida albicans. The
      antimicrobially active components of metapleural secretions were nonpolar and
      interacted with the phospholipid bilayer, causing damage to the structural
      integrity of liposomes and the release of carboxyfluorescein. The data suggest
      that the antimicrobial agents in metapleural secretion act primarily by
      disrupting the structure and function of the phospholipid bilayer of the
      cytoplasmic membrane.

PMID- 7720012
TI  - The identification of bacterial gene expression differences using mRNA-based
      isothermal subtractive hybridization.
AB  - We describe a method for isolating and determining differences in gene expression
      between related bacterial strains. The method is based upon differences in mRNA
      expression. To demonstrate this procedure, cDNA generated from total RNA of
      Listeria monocytogenes serotype 1/2a was hybridized to total RNA from a Tn916
      mutant of serogroup 1/2a (M3) that was deficient in the production of
      listeriolysin O, the product of the hly gene. The single-stranded cDNA fragments
      remaining after hybridization represent the difference in expressed genes between
      the two strains. These subtraction products were used as hybridization probes to
      identify the corresponding hly gene in a Southern hybridization.

PMID- 7720013
TI  - Induction of resistance to hydrogen peroxide and radiation in Deinococcus
      radiodurans.
AB  - Though bacteria of the radiation-resistant genus Deinococcus have a high
      resistance to the lethal and mutagenic effects of many DNA-damaging agents, the
      mechanisms involved in the response of these bacteria to oxidative stress are
      poorly understood. To investigate antioxidant enzyme responses in Deinococcus
      spp., the catalase activity produced by these bacteria was measured and the
      sensitivity of these bacteria to hydrogen peroxide was tested. Deinococcus spp.
      had higher levels of catalase and were more resistant to hydrogen peroxide than
      Escherichia coli K12. The high levels of catalase produced by Deinococcus
      radiodurans were, in part, regulated by growth phase. Cultures of D. radiodurans,
      when pretreated with sublethal levels of hydrogen peroxide, became relatively
      resistant to the lethal effects of hydrogen peroxide and exhibited higher levels
      of catalase than untreated control cultures. These pretreated cells were also
      resistant to lethality mediated by ultraviolet light and gamma-rays. These
      results suggest that Deinococcus spp. possess inducible defense mechanism(s)
      against the deleterious effects of oxidants and ionizing and ultraviolet
      radiation.

PMID- 7720014
TI  - Mental health issues in elderly African Americans.
AB  - In order to provide a context for a discussion of the mental health issues of
      older African Americans, a brief overview of the demographic characteristics and
      psychosocial characteristics of African Americans aged 65 and older is presented.
      After a concise summary of the medical problems present in older African
      Americans, specific concerns regarding diagnostic bias are reviewed. Existing
      epidemiologic data on the prevalence of psychiatric symptoms and disorders are
      summarized. Within this context, specific mental health issues affecting older
      African Americans is presented.

PMID- 7720015
TI  - Ethical considerations with African-American elders.
AB  - African American elders are a diverse group whose values and beliefs are part of
      the ethics of United States society. The interplay between these beliefs and the
      health care system offers many challenges for the geriatrician. Addressing issues
      of autonomy, beneficence, nonmaleficence, truth-telling, confidentiality, and
      justice are important in caring for African American elders.

PMID- 7720016
TI  - The principles of medical ethics and their application to Mexican-American
      elderly patients.
AB  - Within the vigor of the American medical ethical dialogue, awareness that the
      principles of respect for autonomy, beneficence, and justice may reflect some
      cultural bias that, in effect, may not be applicable to Americans of all
      ethnicities is growing. This bias raises the question about what happens when
      these three ethical principles are applied in clinical situations involving
      elderly Mexican-American patients. Four case studies based on actual patient
      encounters are presented to show the manner in which ethical principles may apply
      for Mexican-American patients and to generate discussion by presenting evidence
      that indicates that the fundamental ethical principle that Mexican-American
      elders expect will be applied by their physicians is beneficence, and not respect
      for self-determination.

PMID- 7720017
TI  - Ethical considerations in Asian and Pacific Island elders.
AB  - A brief overview of the demographic and psychosocial characteristics and medical
      problems of African Americans age 65 and older provide the context for a
      discussion of the mental health issues of older African Americans. With this
      background, specific concerns regarding diagnostic bias are reviewed. Existing
      epidemiologic data on the prevalence of psychiatric symptoms and disorders are
      summarized and the specific mental health issues affecting older African
      Americans are described. Specific research strategies are suggested to address
      the areas of absent data.

PMID- 7720018
TI  - African-American elders. Implications for health care providers.
AB  - With the demographic projections that are expected in the next century, health
      care professionals of all disciplines will be caring for a large group of older
      African Americans. Most will be women with multiple chronic illnesses that are,
      and will continue to be, influenced by a number of factors, including race,
      gender, and socioeconomic status. Although the data we have on older African
      Americans have increased significantly over the past several years, a great need
      for studies that examine the complexities of race, health risks, and disease
      course still exists. Health-care providers will begin to avoid stereotypes as
      they begin to appreciate the diversity of this group, which will become
      especially important as the characteristics of the current cohort of elders
      changes in the coming years. It is clear that more and more African Americans are
      living longer and are in better health. An examination of those determinants of
      successful aging that might be applied to elders of all racial and ethnic
      backgrounds must occur. It will be imperative that all facets of the established
      medical system begin to provide and plan for culturally sensitive health care and
      services, which will require data, both quantitative and qualitative, that
      defines the characteristics of older African Americans along with their health
      service needs. Health professional schools will have to adapt curricula to
      include issues of ethnogeriatrics to ensure that all providers are prepared to
      meet the challenge of providing culturally sensitive health care.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7720019
TI  - Health status of Hispanic elders.
AB  - Hispanic elders living in the United States compose a rapidly increasing
      population. They are underinsured and more likely to be living in poverty. Health
      care is hindered in this population by lower access to health services and less
      use of preventive services. Barriers to access are primarily socioeconomic.
      Acculturation exerts an effect, primarily through its association with language
      skills, employment, and education. Cardiovascular disease is the leading cause of
      mortality for Hispanics, who have a higher prevalence of risk factors for
      cardiovascular disease, such as diabetes mellitus, obesity, and hyperlipidemia.
      Although neoplasia is the second most frequent cause of death among Hispanics, as
      it is in whites who are not Hispanic, Hispanics have an overall lower cancer
      rate. Cancer rates are increasing, however. Non-insulin-dependent diabetes
      mellitus is a significant cause of morbidity and mortality in the Hispanic
      population, affecting nearly a quarter of adult Puerto Ricans and Mexican
      Americans. Although higher prevalence of obesity in the Hispanic population
      accounts for some of this difference, some data suggest the possibility of a
      genetic component as well. Assessment of psychological health in Hispanic elders
      is impeded by the lack of instruments designed for this population. Distress is
      often expressed as somatic symptoms. Values traditional to Hispanic culture, such
      as respeto, allocentrism, and familialism, are important to US Hispanic elders,
      many of whom were born in rural Mexico. Our knowledge of determinants of healthy
      aging in this population is still preliminary, but rapidly expanding, in part,
      because of increased attention to ethnicity in health reporting.

PMID- 7720020
TI  - Hispanic-American elders. Implications for health-care providers.
AB  - American health-care practitioners are faced with a rapidly growing, geriatric,
      Hispanic-American population. This group shares certain cultural links but is
      largely heterogeneous and comprised of many subgroups, the largest of which are
      Mexican Americans, Puerto Ricans, and Cuban Americans. Health-care practitioners
      face significant socioeconomic, cultural, and language barriers in providing care
      to these patients. An understanding of Hispanic-American social dynamics, an
      understanding of culture-bound syndromes, and efforts to successfully overcome
      language barriers are essential to optimal patient care. Exploration of the
      ethnic complexity of Hispanic-American subgroups will help to free practitioners
      from medical and racial stereotypes and allow development of cultural insights
      that can strengthen and enrich the doctor-patient relationship.

PMID- 7720021
TI  - Health status of Asians and Pacific Islanders.
AB  - The elder Asian or Pacific-Island American presents a dynamic, interactive
      paradigm of forces beyond medical practice that includes religious, societal, and
      historical factors of delivering health care. The cultural characteristics of
      family and function, perception of time and healing, and the anthropologic
      factors of health beliefs on health behaviors can add to understanding our
      medical patients. Some important trends of environmental factors on expression of
      genetic predisposition to certain illnesses, such as diabetes and gout, can be
      used in health prevention. The significance of diet on certain cancers can be
      better understood using nativity factors. Many of the mental illnesses borne by
      immigrants can be recognized and treated. Significant clinical research
      directions imply an ability of American medicine to target at-risk Asians and
      Pacific Islanders for specific prevention and early diagnoses. The base knowledge
      of differential physiologic changes for aging and disease due to genetic
      predisposition and the correlates of social, cultural, and behavioral factors of
      diseases can then be improved.

PMID- 7720022
TI  - Asian Pacific elders. Implications for health care providers.
AB  - Asian Pacific Islanders are a diverse group that include recent immigrants as
      well as long-term residents. They may be isolated or unsettled in their
      relationships with their own families and unfamiliar with Western medical care
      and thought. Medical care should take into consideration unique features of their
      traditional health benefits, traditional medications, prevalence of medical
      problems, pharmacokinetics and pharmacodynamics, diet, health risks, and health
      promotion. Although they cannot be homogenized into one tidy bundle, certain
      commonalities apply, and are addressed.

PMID- 7720023
TI  - Native-American elders. Health care status.
AB  - This article reviews current data relevant to the health care status of elderly
      Native Americans, a population cohort encompassing American Indians and Alaskan
      Natives/Aleutians. Several topics are addressed, including the history of Native
      American health policy, heart disease, diabetes mellitus, cancer, oral health,
      nutrition, long-term care, and the circumstances of urban Native American elders.

PMID- 7720024
TI  - Ethical and clinical issues with Native-American elders. End-of-life decision
      making.
AB  - This article offers guidance to clinicians for approaching and conducting end-of
      life decision-making conversations with Native American elders. The guidelines
      emphasize the need for flexibility and clarity in communication, avoidance of
      insistence on formal structures and rigid time frames for decision-making,
      sensitivity to the cultural and family situation of the elder, and recognition
      that cultural as well as language interpretation may be necessary. Given the
      great diversity of the tribes and bands as well as languages among native people
      and the paucity of empirical work on this topic, the tentative nature of these
      guidelines is stressed.

PMID- 7720025
TI  - The pathophysiology of diabetic foot ulceration.
AB  - Multiple mechanisms contribute to the etiopathogenesis of diabetic foot
      ulceration. Of these, neuropathy is probably the most important as a contributing
      factor, but it is the combination of neuropathy with other factors that leads to
      ulceration. Trauma in the neuropathic foot may be extrinsic, for example, in
      poorly fitting footwear, or intrinsic, for example, high foot pressures. These
      and other mechanisms are discussed in this article.

PMID- 7720026
TI  - Hyperbaric oxygen therapy for diabetic wounds.
AB  - Hyperbaric oxygen can be a useful adjuvant in the management of diabetic foot
      wounds when coordinated with medical-surgical management of the patient. Elevated
      tissue oxygen tensions improve leukocyte bacterial killing efficiency and enhance
      connective tissue regenerative systems for wound healing. An algorithm for the
      management of diabetic foot wounds is proposed in this article.

PMID- 7720027
TI  - The role of foot surgery in patients with diabetes.
AB  - In conclusion, surgery on the diabetic foot should be looked upon as a required
      addition to quality conservative care. The success that can be gained from proper
      performance of these procedures can be rewarding and often improves the ability
      to salvage limbs that may have otherwise been lost because of ulceration,
      infection, instability, or pain.

PMID- 7720028
TI  - Vascular evaluation and long-term results of distal bypass surgery in patients
      with diabetes.
AB  - The objective of the US Health Department and the American Diabetes Association
      is to reduce the major amputation rate in diabetics by 40% by the year 2000. It
      is the goal of this article to help the reader define the role of proper
      diagnosis and management of vascular disease to meet this challenge.

PMID- 7720029
TI  - Amputations in the diabetic foot.
AB  - Foot amputation in the diabetic population can help maintain a patient's
      independent ambulation and function. Such surgery requires diligence of the
      surgeon and a watchful eye for the development of early and long-term
      complications. Careful adherence to the listed healing parameters can assist the
      surgeon in achieving healing rates of above 90%.

PMID- 7720030
TI  - Diagnosis, classification, and treatment of diabetic peripheral neuropathy.
AB  - Neuropathy is one of the most common long-term complications of diabetes.
      Sensorimotor polyneuropathy first affects the more distal parts of the lower
      extremities and then spreads more centrally and is therefore the most commonly
      involved in diabetic foot problems. Autonomic neuropathy causes increased
      arteriovenous shunting and tissue hypoxia at the feet but also involves other
      systems, such as the gastrointestinal, cardiovascular, and genitourinary systems.
      More than one factor is believed to be involved in its pathogenesis. Good
      glycemic control can prevent the development of the disease or halt its
      progression. Other therapeutic factors, currently under investigation in a large
      clinical trial, include aldose reductase inhibitors and gammalinolenic acid with
      promising results so far.

PMID- 7720031
TI  - Wound dressings and topical agents.
AB  - Topical treatment of wounds is an important aspect of wound care, although
      secondary to surgical and systemic care. Dressing materials come in many forms to
      suit wound types and preferences. No hard evidence exists to place any one
      approach above another. All wounds deserve individualized attention and care
      plans. Likewise, a plethora of solutions exist to augment dressing materials in
      cleansing, antibiosis, and debridement. Traditional agents, including hydrogen
      peroxide, Dakin's solution, and povidone-iodine, are more tissue toxic than their
      common usage would indicate. We prefer frequent dressing changes with natural
      fiber gauze and nontoxic solutions such as saline. The scalpel, curette, and
      rongeur are, in our experience, much preferred to enzymatic agents when
      debridement is needed. We encourage scrutiny of commercial products based on
      clinical merit and effectiveness as documented in the medical literature.
      Platelet derived growth factors are an effective adjunct to wound healing and are
      primarily indicated when the condition of patients and their wounds has otherwise
      been optimized.

PMID- 7720032
TI  - Prescription insoles and footwear.
AB  - Current research emphasizes the importance of prevention in caring for the
      diabetic foot. Prescription footwear has been shown to be a significant factor in
      prevention of both ulcer recurrence and amputation. In addition, scientific
      evidence demonstrates the ability of insole materials to reduce shock and shear,
      the effectiveness of insoles in providing pressure relief, and the ability of
      rocker soles to relieve metatarsal pressure. This evidence, however, is limited
      and is often based on clinical investigation rather than on objective,
      quantitative measurements. Recent advances in biomechanical modeling and in-shoe
      pressure measurement should allow more objective data on a wider variety of
      prescription footwear to become available. The importance of prescription
      footwear as a preventive measure is nonetheless widely recognized. The knowledge
      and experience of pedorthists make them uniquely qualified to provide the needed
      shoes, modifications, and insoles for the long-term management of the diabetic
      foot.

PMID- 7720033
TI  - Total-contact casting, sandals, and insoles. Construction and applications in a
      total foot-care program.
AB  - It must be stressed that these tools do not exist in a vacuum and that no single
      tool is particularly useful unless it is a part of a comprehensive, lifelong foot
      care program. A partnership between the health care provider and the patient is
      essential in making any of these techniques useful. On the positive side, a
      program incorporating these techniques can be very successful with even the most
      difficult population. The very successful Parkland Memorial Hospital program
      provides care for a county hospital population that is often difficult in terms
      of compliance. Without question, the reasons for incorporating such a program in
      a public facility are sound. Amputations are avoided; and patients remain or
      become more functional, thus decreasing hospital cost and patient morbidity and
      mortality and increasing the patient's potential for contributing to society.
      Similarly, in private facilities, once the program is established, costs need not
      run high and considerable amounts can be saved by helping heal and/or prevent the
      horrendous sequelae of diabetic neuropathies.

PMID- 7720034
TI  - Imaging techniques in the diabetic foot.
AB  - Osteomyelitis underlies the majority of diabetic foot ulcers, and it is usually
      not detected clinically. Leukocyte scanning with indium oxyquinoline has greater
      sensitivity than radiographs, bone scans, and MR imaging in diagnosing
      osteomyelitis in diabetic foot ulcers. All ulcers that expose bone, and perhaps
      moderately deep ulcers as well, should be treated for osteomyelitis because of
      the high prevalence of this infection (100% and 82%, respectively). Osteomyelitis
      should be evaluated for in shallow ulcers by radiographs, followed by leukocyte
      scans if the former tests are negative. Bone biopsies should be performed if
      possible because cultures may guide antibiotic treatment.

PMID- 7720035
TI  - Bone and soft-tissue infections of the lower extremity in diabetics.
AB  - The foot is the most common site of infection in the diabetic individual, and one
      of every four diabetics eventually seeks medical care for a foot problem. This
      article examines pathologic conditions of the lower extremity from a variety of
      views, including pathophysiology, classification, microbiology, infections,
      osteomyelitis, treatment, and prevention strategies.

PMID- 7720036
TI  - Primary chemotherapy for early and advanced breast cancer.
AB  - While locally advanced breast cancer (LABC) represents a small fraction of
      patients with breast cancer in industrialized nations, in developing countries it
      might constitute up to 50% of incident cases. The definition includes patients
      with stage IIB, III, and some with limited stage IV breast cancer. Inflammatory
      breast cancer (IBC) is part of LABC, but it is often reported separately, because
      of its dismal prognosis. LABC can be considered technically operable (stage II
      and IIIA), or inoperable (stage IIIB, IV and IBC). For the last two decades,
      patients with inoperable LABC and IBC have been treated with increasing frequency
      with systemic therapy first, followed by regional therapy, either surgical
      resection or radiotherapy. Most treatment programs also included adjuvant
      systemic therapy. The majority of patients with LABC and IBC respond to primary
      chemotherapy, and most can be rendered disease-free initially. Local control
      rates exceed 80% with modern combined-modality treatment strategies. Since most
      tumors are downstaged, some patients can be treated with breast-conserving
      treatments. The optimal sequence of local and systemic treatments has not been
      defined. Combined-modality therapies improve the treatment and the outcome for
      patients with LABC. Whether the sequence of utilization of various treatments
      influences outcome remains to be established. The administration of systemic
      therapies first also provides a useful biological model to assess the effects of
      systemic treatments on the primary tumor and regional metastases, since these are
      available for serial non-invasive evaluation and sampling of tumor tissue.

PMID- 7720037
TI  - Comparative pathology of mammary tumorigenesis in transgenic mice.
AB  - Mammary tumors arise in transgenic mice bearing growth factors, proto-oncogenes,
      oncogenes and tumor suppressor genes. The tumors arise from hyperplasias. The
      tumor natural history and histogenesis are oncogene specific. Interactions
      between oncogenes may impede or accelerate tumorigenesis.

PMID- 7720038
TI  - The immunogenicity of MUC1 peptides and fusion protein.
AB  - Mucin 1 (MUC1) is highly expressed in breast cancer, has an ubiquitous
      distribution and, due to altered glycosylation, peptides within the VNTR are
      exposed. These peptides are the target for anti-MUC1 antibodies, which give a
      differential reaction on cancer compared with normal tissue. The amino acids,
      APDTR or adjacent amino acids, are highly immunogenic in mice for antibody
      production (after immunisation with either breast cancer cells, human milk fat
      globule (HMFG) or the VNTR peptide). In addition, human studies show that this
      region of the MUC1 VNTR functions as target epitopes for cytotoxic T cells. We
      have performed preclinical and clinical studies to examine the immune responses
      to MUC1 in mice and humans: (a) MUC1+ 3T3 or P815+ 3T3 cells in syngeneic mice
      are rejected, with the generation of both cytotoxic T lymphocyte (CTL) and DTH
      responses and a weak antibody response and a weak antibody responses; this type
      of immunity gives rise to total resistance to re-challenge with high doses of
      these tumors; (b) immunisation with peptides (VNTR x 2), a fusion protein (VNTR x
      5), or HMFG leads to no CTLs, DTH, good antibody production and weak tumour
      protection (to 10(6) cells, but not 5 x 10(6) cells) (possibly a TH2 type
      response); (c) immunisation with mannan-fusion protein (MFP) gives rise to good
      protection (resistance to 50 x 10(6) cells), CTL and DTH responses and weak
      antibody responses (possibly a TH1 type response, similar in magnitude to that
      obtained after tumor rejection); (d) established tumors can be rapidly rejected
      by delayed treatment of MFP; (e) the CTL responses are MHC restricted (in
      contrast to the human studies); (f) APDTR appears not to be the T cell reactive
      epitope in mice. On the basis of these findings, two clinical trials are in
      progress: (a) VNTR x 2 (diphtheria toxoid) which gives rise to some T cell
      proliferation, DTH and antibody responses in some patients and (b) an MFP trial.
      The ability to alter the immune response towards cellular immunity with mannan or
      to humoral immunity with peptides, allows the immune response to be selectively
      manipulated.

PMID- 7720039
TI  - Is episialin/MUC1 involved in breast cancer progression?
AB  - Episialin, also designated MUC1, CA 15-3 antigen and PEM, is an established serum
      marker for breast cancer. Its function and possible involvement in tumor
      progression has not yet been completely established. The molecule is an extended
      rod-like molecule protruding high above the cell surface. It is often highly
      overexpressed in breast cancer relative to normal breast epithelium cells.
      Overexpression of episialin on cells in vitro reduces cell-cell and cell
      extracellular matrix adhesion, because the rod-like molecule masks the adhesion
      receptors. Episialin also exerts its anti-adhesion effect in vivo. In certain
      human tumors, where episialin was present at the basal side of the cell, abnormal
      contacts between the plasma membrane and the stroma were observed. As a
      consequence of its anti-adhesion properties, episialin overexpression reduces the
      sensitivity of the cells for cytotoxic lymphocytes. This might be one of the
      reasons why episialin transfected cells are more potent to form experimental
      metastases after i.v. injection into nude mice.

PMID- 7720040
TI  - Biology of mouse mammary tumor virus (MMTV).
AB  - Mouse mammary tumor viruses (MMTV) replicate in the mammary gland, appear as
      infectious particles in mother's milk and invade the sucking pups from the
      intestinal tract. The immune system is essential for MMTV in the gut to reach the
      mammary gland. These properties make the life cycle of MMTV unique. We review the
      oncologically and immunologically intriguing events caused by MMTV in relation to
      the life cycle of the virus.

PMID- 7720041
TI  - The biological action of cDNAs from mutated estrogen receptors transfected into
      breast cancer cells.
AB  - While tamoxifen may inhibit breast cancer proliferation, mutations in the
      estrogen receptor could potentially result in breast cancer cells which can
      circumvent the tamoxifen blockade. Previously, we identified a mutation at codon
      351 in the estrogen receptor from a tamoxifen-stimulated human breast cancer.
      This receptor was stably transfected into the estrogen receptor-negative human
      breast cancer cell line MDA-MB-231 (clone 10A). Clones were compared to stably
      transfected cell lines containing either the wild type or codon 400 mutant
      estrogen receptor to study the effect of either estradiol or the tamoxifen
      analogue, fixed-ring 4-hydroxytamoxifen ((fr)4-OH TAM), on cell growth and
      reporter gene activation. (fr)4-OH TAM reduced the growth rate in cell lines
      containing mutant estrogen receptors, while the cell line containing the wild
      type estrogen receptor is minimally influenced by (fr)4-OH TAM. We then needed to
      show that the ligand-estrogen receptor interaction resulted in estrogen receptor
      activation. As a ligand-dependent transcription factor, estrogen receptor
      activation is measured by its ability to stimulate reporter gene (luciferase)
      transcription when bound to an estrogenic ligand. We found that the wild type
      estrogen receptor is activated by estradiol but not by the tamoxifen analogue,
      while the codon 351 estrogen receptor is activated by both (fr)4-OH TAM and
      estradiol.

PMID- 7720042
TI  - Amplification of chromosome band 11q13 and a role for cyclin D1 in human breast
      cancer.
AB  - In this paper we describe how research on the mouse mammary tumor virus model of
      breast cancer resulted in the identification of an amplified region of DNA on
      human chromosome 11 band q13. This amplification occurs in approximately 15% of
      primary breast cancers. Several candidate oncogenes map within the amplicon but
      by analysing expression of these genes a strong case can be made for a role for
      cyclin D1 in tumorigenesis. Immunohistochemical staining indicates that cyclin D1
      is expressed at elevated levels in around 40% of breast cancers, including those
      with the 11q13 amplification. The potential function of cyclin D1 as a regulator
      of early cell division cycle events would be consistent with a role in neoplasia.

PMID- 7720043
TI  - Mutations in breast cancer.
AB  - The genetics of spontaneous breast cancer is reviewed. We have identified three
      regions of amplification and nine chromosomal arms with deletions in the genome.
      The significance and interrelations of these mutations is discussed with respect
      to the complex genetics of breast carcinoma. Recent work identifying a commonly
      deleted region between D17S846 and D17S746 is presented, which is approximately
      0.5-1.0 Mb centromeric to the newly described BRCA1 gene candidate. Possible
      explanations for the different locations of our deleted region and the BRCA1 gene
      are presented.

PMID- 7720044
TI  - Clonal analysis of benign and malignant human breast tumors by means of
      polymerase chain reaction.
AB  - Clonal analysis was conduced on a variety of benign and malignant human breast
      tumors using the method based on restriction fragment length polymorphism (RFLP)
      of the X 120 chromosome-linked phosphoglycerokinase gene and on random
      inactivation of the gene by methylation. Breast carcinoma was shown to be
      monoclonal in origin, consistent with a somatic mutational theory. Precancerous
      lesions such as atypical ductal hyperplasia and multiple intraductal papilloma
      were also found to be monoclonal, indicating that certain genetic changes had
      been accumulated in these lesions. Solitary intraductal papilloma was found to be
      monoclonal. Since this tumor is composed of two types of cells, luminal
      epithelial cells and myoepithelial cells, it was suggested that the origin of
      solitary intraductal papilloma is a precursor cell which is capable of
      differentiating into both luminal and myoepithelial cells. The fact that
      fibroadenoma is polyclonal indicates that this tumor is not neoplasia but
      hyperplasia of a lobule. Epithelial component of phyllodes tumor was found to be
      polyclonal but stromal component was found to be monoclonal. Thus, phyllodes
      tumor is considered to be a neoplasm of stromal cells but not of epithelial
      cells.

PMID- 7720045
TI  - Epidemiology of breast cancer in Japan.
AB  - The mortality and incidence of breast cancer are high in Western industrialized
      countries and relatively low in developing countries in Asia and other parts of
      the world. In Japan the mortality of breast cancer has gradually been increasing,
      but is still much lower compared with that of Western countries. Within Japan the
      mortality of breast cancer is higher in urban areas than in non-urban areas. The
      future estimation of cancer incidence in Japan predicts that breast cancer will
      become a leading cancer in the near future.

PMID- 7720046
TI  - The etiopathogenesis of breast cancer prevention.
AB  - Breast cancer, the most frequent malignancy diagnosed in women, continues to
      increase in incidence in all industrialized nations. The fact that this disease
      becomes incurable once it has spread to regional or distant sites indicates that
      its complexity is beyond our present level of knowledge. A better understanding
      of the etiopathogenesis and biology of breast cancer is required in order to
      develop a rational basis for its prevention and therapy. The observation that
      early parity reduces the risk of developing breast cancer indicates that
      reproductive and hormonal conditions might play an important role in its
      prevention. The elucidation of the mechanisms mediating this protection requires
      the availability of adequate experimental models. The induction of rat mammary
      carcinomas with chemical carcinogens has proven to be useful for these purposes,
      especially since, in this model, full-term pregnancy or treatment of virgin rats
      with a placental hormone, human chorionic gonadotropin (hCG), prior to the
      administration of the carcinogen protects the mammary gland from tumor
      development. Since both pregnancy and hCG treatment induce differentiation of the
      mammary gland, this process is considered to be essential for the inhibition of
      the neoplastic process. The possibility of preventing breast cancer by treating
      young nulliparous females with hormones that mimic a full term pregnancy is of
      practical interest to the human female population, but it requires a thorough
      knowledge of the development of the human breast. Our studies indicate that the
      breast of postpubertal nulliparous women is composed of lobular structures
      reflecting different stages of development. Type I lobules are the most
      undifferentiated. Type 2 lobules evolve from the previous ones; they are composed
      of a higher number of ductular structures per lobule. They progress to lobules
      types 3 and 4, which are present in the breast during pregnancy and lactation.
      The type 1 lobule, considered to be the site of origin of ductal carcinomas,
      predominates in the breast of nulliparous women of all ages. In parous women, the
      type 3 lobule is the most frequent. Primary cultures derived from breast tissues
      composed of type 1 lobules express phenotypes of cell transformation not observed
      in cells derived from type 3 lobules. These data acquire relevance in the light
      that women with a history of early pregnancy are at a lower risk of developing
      breast cancer than nulliparous women, an effect attributed to differences in the
      degree of differentiation of the breast. Pregnancy furthers the differentiation
      of type 1 lobules to type 3, making them refractory to neoplastic
      transformation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7720047
TI  - Controversies in the local management of invasive and non-invasive breast cancer.
AB  - Since the recent acceptance of partial mastectomy (lumpectomy or segmentectomy)
      as equivalent to mastectomy for survival, design of the local management of
      breast cancers has centered around concerns of local recurrence. There has been
      wide acceptance of the tumorectomy or lumpectomy approach by most authors in
      North America, while in Italy, following the Milan trials, there has been a
      preference for a segmental or quadrantectomy approach. The latter preferentially
      includes more ductal tissue toward and distant from the nipple and has shown a
      local recurrence rate less than 50% as great as that seen with lumpectomy.
      Radiotherapy dosages and techniques are of concern as well. If extensive ductal
      carcinoma in situ is a determinant of local recurrence, and if DCIS spreads
      preferentially along ducts in a radial fashion, then the extent of DCIS is most
      likely to be preferentially arrayed toward the nipple as well as in tissue on the
      other side of a tumor mass away from the nipple--such has been our knowledge of
      the ramifications of the ductal tree, in a radial fashion around the nipple.
      Acceptable cosmesis after a segmental approach to excision may be more difficult
      to obtain, but has been acceptable in some groups of patients. We may soon see a
      situation in which the operation is tailored to the specifics of an individual
      patient. The size of a resection, based on an even margin around a tumor mass
      (lumpectomy) or the number of degrees subtended by the arc representing the
      peripheral aspect of a segmental excision will depend on the size of the dominant
      lesion being resected, the size of the breast and any available data concerning
      the likely extent of the lesion, with DCIS having a special concern.

PMID- 7720048
TI  - Heterogeneity of duct carcinoma in situ (DCIS): relationship of grade and subtype
      analysis to local recurrence and risk of invasive transformation.
AB  - Morphologic analysis of nuclear grade and extent of necrosis can provide
      reproducible classification of subclinical duct carcinoma in situ (DCIS) which
      strongly separates DCIS into three risk groups. For subclinical lesions of small
      size, risk is largely limited to local recurrences only, half of which, however,
      are invasive events. Local recurrences are seen much more frequently with high
      grade DCIS. Most local recurrences following breast conservation therapy
      represent residual disease in the immediate vicinity of the biopsy site. Stromal
      and cellular host reactions may provide additional prognostic information.

PMID- 7720049
TI  - Decision tree model describing alternate health care choices made by oncology
      patients.
AB  - What common sense decision strategies do patients with cancer use when they are
      making health care choices that include alternate therapies? Existing research
      indicates that oncology patients are making alternate choices while associated
      with biomedicine. Often patients' decision strategies are exploited by the
      alternate system to promote and market alternate products. Although some of these
      practices are benign, others are dangerous or may interfere or delay successful
      treatment in biomedicine. Therefore, it seems important for biomedical
      professionals to understand patients' common sense decision patterns. A decision
      tree model, outlining patients' decision strategies, has recently been developed
      through intensive interviews with 300 patients who were diagnosed with cancer of
      the respiratory and digestive systems. The two-phase methodology included, first,
      a context sensitive approach to develop the model, followed by a predictive
      approach testing the model developed in the first phase on a separate yet similar
      random sample of patients. The discussion in this article focuses on the
      research, the patterns of the decision tree model, and the implications and
      adaptability of this model to nursing practice.

PMID- 7720050
TI  - Nurses' perceptions of the meaning of quality of life for bone marrow transplant
      survivors.
AB  - Nurses play an integral role in the care of bone marrow transplant (BMT) patients
      from pre-transplant to posttransplant. The purpose of this study was to explore
      the nurses' perceptions of the impact of transplant on the quality of life (QOL)
      of survivors. The conceptual framework for the study was the model of QOL
      developed by Ferrell, Grant, Schmidt, Rhiner, Whitehead, and Forman (1992). It
      depicts the QOL domains of physical well-being, psychological well-being, social
      concerns, and spiritual well-being. One hundred fifty nurses responded to a
      mailed survey. The items were based on the Quality of Life-BMT Survey used
      previously with patients. Nurses' and patients' responses to the same item were
      compared. Results reflect that transplant nurses generally perceived patients as
      having a poorer QOL than they actually reported. Nurses described transplant as
      having both positive and negative consequences. Transplant was seen as providing
      patients with a second chance at life and an opportunity to increase their QOL.
      Nurses described negative consequences as resulting from physical losses,
      psychological distress, financial distress, and loss of relationships. The
      findings of the study have implications for training future transplant nurses and
      for improving nursing care for transplant patients.

PMID- 7720051
TI  - Care of the adolescent undergoing an allograft procedure.
AB  - During the last 25 years, substantial progress has been made in the detection and
      treatment of bone tumors in adolescents and young adults. Due to more effective
      chemotherapy treatments, patients are now surviving these illnesses and living
      quality lives. In the past, the only surgical option for treatment of these
      tumors was amputation. Today, however, limb-sparing procedures such as allograft
      implantation, together with effective chemotherapy treatments, provide patients
      with another treatment option. The allograft procedure includes removing the
      tumor and affected bone and replacing it with bone procured from deceased donors.
      During the following 2 years, the body does the work of incorporating the
      allograft and replacing it, at least in part, with new host bone. After a long
      rehabilitation process, the patient will have a functioning limb. Nursing care of
      the adolescent undergoing allograft procedure encompasses meeting important
      physical and psychosocial needs. Adolescents are often still dealing with the
      emotional and physical stress of having cancer and chemotherapy or chemotherapy
      side effects at the time of surgery. They are concerned not only with their
      immediate recovery but also with their long-term prognosis. All treatment
      modalities, including allograft surgery, impinges on the normal developmental
      tasks of adolescents. The nursing challenge is to help the adolescent balance the
      limits of their illness and recovery with normal developmental needs.

PMID- 7720052
TI  - Body image disturbances in young adults with cancer. Implications for the
      oncology clinical nurse specialist.
AB  - The impact of the diagnosis of cancer and its treatments on the body image of
      young adults (18-29 years) diagnosed with cancer is relatively unknown. This
      descriptive comparative study examined body image scores of young adults
      diagnosed with cancer and young adults without cancer. The conceptual framework
      for this study was taken from body image and developmental theory. Secord and
      Jourard's body cathexis/self-cathexis scales and a demographic sheet were mailed
      to 162 young adults diagnosed with cancer and to 150 young adults without cancer.
      A t test was used to compare the mean scores between the two groups. A
      statistically significant difference was found between the mean scores reported
      by the young adults diagnosed with cancer for the body cathexis and self-cathexis
      scales. The self-cathexis and body cathexis scores indicated that the young
      adults diagnosed with cancer had a more positive body image than the young adults
      without cancer. The mean scores were also compared in relation to the demographic
      data collected using t tests and analysis of variance. Within the group diagnosed
      with cancer, male subjects demonstrated a more secure body-cathexis (p value of
      0.012) and married subjects demonstrated a more secure self-cathexis than the
      single subjects did (p value of 0.04). No statistically significant difference
      was found within the group without cancer related to demographic variables.
      Implications for the oncology clinical nurse specialist are explored.

PMID- 7720053
TI  - Skin and wound care in radiation oncology.

PMID- 7720054
TI  - Allergy as a risk factor for nursing care problems in the elderly cancer patient.
AB  - The purpose of this secondary analysis was to determine (a) the nursing diagnoses
      in elderly patients with cancer and (b) whether elderly cancer patients with a
      current or past history of allergy were at risk for selected nursing problems. A
      retrospective clinical data base from 59 patients (32 male, 27 female) with a
      diagnosis of cancer and an age range of 55-85 years with a mean age of 65.6 years
      was examined. The most frequently occurring priority nursing diagnoses identified
      by Clinical Nurse Specialists (CNS) were Pain, Risk for Infection, and Impairment
      of Skin Integrity. When examining the comprehensive list of priority and
      nonpriority nursing diagnoses, identified for these patients with cancer, it was
      found that those with a history of allergy were significantly more likely to have
      a high risk for infection than those without a history of allergy. Two other
      diagnoses (knowledge deficit and potential fluid volume deficit) occurred in a
      significant number in the allergy group, but there was no occurrence of these two
      diagnoses in the nonallergy group. The limitations of assessing immunologic
      status as a part of regular nursing assessments were discussed. Recommendations
      were provided for future research in the area of immunology, aging, and nursing
      diagnoses.

PMID- 7720055
TI  - Decision making in consenting to experimental cancer therapy.

PMID- 7720056
TI  - It's ok to say no! A discussion of ethical issues arising from informed consent
      to chemotherapy.
AB  - This article is written in response to anecdotal evidence from patients, reports
      from nurses, sociological studies, and documentation from oncologists, which all
      suggest that the process of refusing treatment for chemotherapy is not an easy
      one. There is substantial evidence to suggest that pressures that are
      counterproductive to informed consent are having an impact on the decision making
      of vulnerable individuals coping with the stress of terminal illness through
      cancer. Informed consent is a basic ethical principle underpinning any medical or
      nursing intervention (Johnstone M. Bioethics: a nursing perspective. Sydney:
      Harcourt Brace Jovanovich, 1989). The following focus on informed consent is an
      attempt to begin to address the present hiatus which exists in the health
      literature on ethical issues surrounding the modality, chemotherapy (Young D. An
      ethical approach to chemotherapy in private practice. J Natl Cancer Inst
      1992;84:810). Recent research suggests that the holistic orientation of nurses,
      in comparison to the reductionist stance of physicians, allows them to be
      emotionally close to their patients and hence, more aware of the difficulties
      individuals experience in coping with stressful regimens (Uden G, Norberg A,
      Lindseth A, Marhaug V. Ethical reasoning in nurses' and physicians' stories about
      care episodes. J Adv Nurs 1992;17:1028-34). Consequently, it is anticipated that
      ethical issues in relation to chemotherapy, a modality that has been described as
      distressing and capable of seriously compromising quality of life (Burish T, Tope
      D. Psychological techniques for controlling the adverse side effects of cancer
      chemotherapy: findings from a decade of research. J Pain Sympt Man 1992;7:287
      301), will have an impact on the working life of many oncology nurses.

PMID- 7720057
TI  - Molecular mechanisms of the immune response. Dedicated to Micheal Crumpton.
      Introduction.

PMID- 7720058
TI  - Evolution and function of the HLA region.

PMID- 7720059
TI  - Accessory signals for growth and differentiation of human T lymphocytes.
AB  - Accessory signals represent the level at which functional immune responses are
      regulated. Impairment of ligand-receptor interactions or, alternatively,
      intracellular signalling processes plays a pivotal part in vivo. Thus, tumour
      tolerance might result from missing co-stimulatory signals, which is supported by
      numerous recent data. Conversely, blocking accessory receptors might provide the
      means to influence allograft rejection. Upregulation of accessory receptors and
      their ligands is a hallmark of inflammatory reactions. Finally, given that
      particular microenvironments are characterized by the presence of particular
      combinations of ligand molecules for critical accessory receptors on T
      lymphocytes, one could envisage novel approaches to local immune intervention.
      All these perspectives, however, are based on our understanding of how accessory
      receptors are composed and interact with intracellular enzymes, which all
      together transmit critical signals to the nucleus, and on an understanding of how
      these signals contribute to functional T cell behaviour.

PMID- 7720060
TI  - Regulation and function of p21ras in T lymphocytes.
AB  - T cell activation is triggered by antigen stimulation and is characterized by the
      production of a wide range of cytokines and other immunomodulators crucial for
      the growth and development of other haemopoietic cells. Activation also induces
      the T cells to express, on their cell surface, receptors that enable the T cell
      to respond to the various cytokines generated during an immune response. One well
      characterized event that occurs when mature T cells are activated is the
      production of the cytokine IL2 and the acquisition by the T cell of IL2
      receptors. Interaction between IL2 and its cellular receptor then directs T cell
      growth. Expression of the IL2 gene in T cells is regulated by signalling pathways
      that originate from the T cell antigen receptor complex (TCR). This review
      discusses the role of p21ras in these events. The TCR regulates the activity of
      p21ras, and a range of experiments have shown that p21ras couples the TCR to an
      intracellular kinase cascade involving the serine/threonine kinase Raf-1 and the
      MAP kinase ERK2. Analysis of more distal receptor signals shows that p21ras
      controls a signalling pathway that cooperates with a calcium/calcineurin
      controlled signalling system to stimulate the transcriptional factor NFAT and
      hence the IL2 gene. These studies identify p21ras as a critical signalling
      molecule in immune cells.

PMID- 7720061
TI  - Control of T cell development by non-receptor protein tyrosine kinases.
AB  - Stimulation of the T cell antigen receptor leads to several possible outcomes.
      This is especially true in thymocytes, where ligand occupancy of the receptor may
      promote survival or provoke cell death. Insight into the circuitry of T cell
      receptor signalling has been achieved in transgenic mouse model systems. In
      particular, two SRC-family protein tyrosine kinases, p59fyn and p56lck, have been
      shown to participate in controlling mature thymocyte proliferation and immature
      thymocyte development, respectively. Analysis of the function of p56lck has been
      especially instructive and has yielded data consistent with a model in which this
      kinase serves as the gatekeeper at a developmental checkpoint wherein T cell
      receptor beta chain synthesis promotes maturation and cell division. In addition,
      a remarkably coherent data set supports the view that p56lck regulates allelic
      exclusion at the T cell receptor beta locus. Further testing of putative
      signalling molecules in transgenic mice promises to permit elucidation of the
      biochemical distinctions between positively and negatively selecting stimulation
      pathways active during T cell development.

PMID- 7720063
TI  - Uncomplicated acute myocardial infarction: a critical path.

PMID- 7720062
TI  - T lymphocyte activation: the role of tyrosine phosphorylation.

PMID- 7720064
TI  - Radiofrequency catheter ablation: concepts and nursing implications.

PMID- 7720065
TI  - GTPase cascades choreographing cellular behavior: movement, morphogenesis, and
      more.

PMID- 7720066
TI  - CREB as a memory modulator: induced expression of a dCREB2 activator isoform
      enhances long-term memory in Drosophila.
AB  - Genetic studies of memory formation in Drosophila have revealed that the
      formation of a protein synthesis-dependent long-term memory (LTM) requires
      multiple training sessions. LTM is blocked specifically by induced expression of
      a repressor isoform of the cAMP-responsive element-binding protein (CREB). Here,
      we report an enhancement of LTM formation after induced expression of an
      activator isoform of dCREB2. Maximum LTM is achieved after one training session,
      and its formation depends on phosphorylation of the activator transgene. A model
      of LTM formation based on differential regulation of CREB isoforms is proposed.

PMID- 7720067
TI  - Xklp1, a chromosomal Xenopus kinesin-like protein essential for spindle
      organization and chromosome positioning.
AB  - Xklp1 is a novel Xenopus kinesin-like protein with a motor domain at the amino
      terminus, nuclear localization sequences in the stalk, and a putative zinc finger
      like sequence in the tail. It is nuclear during interphase and chromosomal during
      mitosis. During late anaphase, a fraction of the protein relocalizes to the
      spindle interzone and accumulates in the midbody during telophase. Depletion of
      Xklp1 protein by antisense oligo knockout in oocytes leads to defective mitosis
      during the first cell cycles following fertilization. The bipolarity of spindles
      assembled in vitro in the presence of anti-Xklp1 antibodies is unstable, and the
      chromosomes fail to congress on the metaphase plate.

PMID- 7720068
TI  - DNA binding and meiotic chromosomal localization of the Drosophila nod kinesin
      like protein.
AB  - The Drosophila no distributive disjunction (nod) gene encodes a kinesin-like
      protein that has been proposed to push chromosomes toward the metaphase plate
      during female meiosis. We report that the nonmotor domain of the nod protein can
      mediate direct binding to DNA. Using an antiserum prepared against bacterially
      expressed nod protein, we show that during prometaphase nod protein is localized
      on oocyte chromosomes and is not restricted to either specific chromosomal
      regions or to the kinetochore. Thus, motor-based chromosome-microtubule
      interactions are not limited to the centromere, but extend along the chromosome
      arms, providing a molecular explanation for the polar ejection force.

PMID- 7720069
TI  - Interactions between the nod+ kinesin-like gene and extracentromeric sequences
      are required for transmission of a Drosophila minichromosome.
AB  - In this study, we demonstrate a role for extracentromeric sequences in chromosome
      inheritance. Genetic analyses indicate that transmission of the Drosophila
      minichromosome Dp1187 is sensitive to the dosage of nod+, a kinesin-like gene
      required for the meiotic transmission of achiasmate chromosomes. Minichromosome
      deletions displayed increased loss rates in females heterozygous for a loss-of
      function allele of nod (nod/+). We have analyzed the structures of nod-sensitive
      deletions and conclude that multiple regions of Dp1187 interact genetically with
      nod+ to promote normal chromosome transmission. Most nod+ interactions are
      observed with regions that are not essential for centromere function. We propose
      that normal chromosome transmission requires forces generated outside the
      kinetochore, perhaps to maintain tension on kinetochore microtubules and
      stabilize the attachment of achiasmate chromosomes to the metaphase spindle.

PMID- 7720070
TI  - A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata
      (CDPX) and implications for warfarin embryopathy.
AB  - X-linked recessive chondrodysplasia punctata (CDPX) is a congenital defect of
      bone and cartilage development characterized by aberrant bone mineralization,
      severe underdevelopment of nasal cartilage, and distal phalangeal hypoplasia. A
      virtually identical phenotype is observed in the warfarin embryopathy, which is
      due to the teratogenic effects of coumarin derivatives during pregnancy. We have
      cloned the genomic region within Xp22.3 where the CDPX gene has been assigned and
      isolated three adjacent genes showing highly significant homology to the
      sulfatase gene family. Point mutations in one of these genes were identified in
      five patients with CDPX. Expression of this gene in COS cells resulted in a heat
      labile arylsulfatase activity that is inhibited by warfarin. A deficiency of a
      heat-labile arylsulfatase activity was demonstrated in patients with deletions
      spanning the CDPX region. These data indicate that CDPX is caused by an inherited
      deficiency of a novel sulfatase and suggest that warfarin embryopathy might
      involve drug-induced inhibition of the same enzyme.

PMID- 7720071
TI  - Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular
      dystrophy type 2A.
AB  - Limb-girdle muscular dystrophies (LGMDs) are a group of inherited diseases whose
      genetic etiology has yet to be elucidated. The autosomal recessive forms (LGMD2)
      constitute a genetically heterogeneous group with LGMD2A mapping to chromosome
      15q15.1-q21.1. The gene encoding the muscle-specific calcium-activated neutral
      protease 3 (CANP3) large subunit is located in this region. This cysteine
      protease belongs to the family of intracellular calpains. Fifteen nonsense,
      splice site, frameshift, or missense calpain mutations cosegregate with the
      disease in LGMD2A families, six of which were found within La Reunion island
      patients. A digenic inheritance model is proposed to account for the unexpected
      presence of multiple independent mutations in this small inbred population.
      Finally, these results demonstrate an enzymatic rather than a structural protein
      defect causing a muscular dystrophy, a defect that may have regulatory
      consequences, perhaps in signal transduction.

PMID- 7720072
TI  - Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking
      gelsolin.
AB  - Gelsolin, an 82 kDa actin-binding protein, has potent actin filament-severing
      activity in vitro. To investigate the in vivo function of gelsolin, transgenic
      gelsolin-null (Gsn-) mice were generated and found to have normal embryonic
      development and longevity. However, platelet shape changes are decreased in Gsn-
      mice, causing prolonged bleeding times. Neutrophil migration in vivo into
      peritoneal exudates and in vitro is delayed. Gsn- dermal fibroblasts have
      excessive actin stress fibers and migrate more slowly than wild-type fibroblasts,
      but have increased contractility in vitro. These observations establish the
      requirement of gelsolin for rapid motile responses in cell types involved in
      stress responses such as hemostasis, inflammation, and wound healing. Neither
      gelsolin nor other proteins with similar actin filament-severing activity are
      expressed in early embryonic cells, indicating that this mechanism of actin
      filament dynamics is not essential for motility during early embryogenesis.

PMID- 7720073
TI  - Riding the polar winds: chromosomes motor down east.

PMID- 7720074
TI  - The torso receptor tyrosine kinase can activate Raf in a Ras-independent pathway.
AB  - Activation of the receptor tyrosine kinase (RTK) torso defines the spatial
      domains of expression of the transcription factors tailless and huckebein.
      Previous analyses have demonstrated that Ras1 (p21ras) operates upstream of the D
      Raf (Raf1) serine/threonine kinase in this signaling pathway. By using a recently
      developed technique of germline mosaics, we find that D-Raf can be activated by
      torso in the complete absence of Ras1. This result is supported by analysis of D
      Raf activation in the absence of either the exchange factor Son of sevenless
      (Sos) or the adaptor protein drk (Grb2), as well as by the phenotype of a D-Raf
      mutation that abolishes binding of Ras1 to D-Raf. Our study provides in vivo
      evidence that Raf can be activated by an RTK in a Ras-independent pathway.

PMID- 7720075
TI  - Multiallelic recognition: nonself-dependent dimerization of the bE and bW
      homeodomain proteins in Ustilago maydis.
AB  - In the plant pathogenic fungus Ustilago maydis, sexual and pathogenic development
      are controlled by the multiallelic b mating-type locus. The b locus encodes a
      pair of unrelated homeodomain proteins termed bE and bW, with allelic differences
      clustering in the N-terminal domains of both polypeptides. Only combinations of
      bE and bW of different allelic origin are active. We have investigated the
      underlying molecular mechanism for this intracellular self/nonself recognition
      phenomenon. By using the two-hybrid system, we were able to show that bE and bW
      dimerize only if they are derived from different alleles. Dimerization involves
      the N-terminal variable domains. Different point mutants of bE2 were isolated
      that function in combination with bW2. The majority of such bE2 mutant
      polypeptides were also able to form heterodimers with bW2 in the two-hybrid
      system. Nonself-dependent dimerization of bE and bW was supported with a
      biochemical interaction assay with immobilized proteins. Our results suggest a
      model for self/nonself recognition in which variable cohesive contacts direct
      dimerization.

PMID- 7720076
TI  - Expression cloning of Siamois, a Xenopus homeobox gene expressed in dorsal
      vegetal cells of blastulae and able to induce a complete secondary axis.
AB  - Using an expression cloning strategy that relies on a functional assay, we have
      cloned a novel Xenopus homeobox-containing gene, Siamois. Embryos injected in a
      ventral-vegetal blastomere with as little as 5 pg of Siamois mRNA develop a
      complete secondary axis, but the progeny of the injected cells do not participate
      in the secondary axis formation. In normal development, Siamois mRNA is first
      detected shortly after the midblastula transition, which is earlier than mRNAs
      for goosecoid or Xbrachyury, and is present most abundantly in the dorsal
      endoderm of early gastrulae. The activation of this gene can be obtained cell
      autonomously in dispersed embryo cells. These results indicate that Siamois may
      play an important role in the formation of the Nieuwkoop center.

PMID- 7720077
TI  - Mutations in aurora prevent centrosome separation leading to the formation of
      monopolar spindles.
AB  - We show that female sterile mutations of aurora (aur) are allelic to mutations in
      the lethal complementation group ck10. This lies in a cytogenetic interval, 87A7
      A9, that contains eight transcription units. A 250 bp region upstream of both aur
      and a divergent transcription unit corresponds to the site of a specific
      chromatin structure (scs') previously proposed to be a barrier to insulate
      enhancers of the major hsp70 gene at 87A7. Syncytial embryos derived from aur
      mothers display closely paired centrosomes at inappropriate mitotic stages and
      develop interconnected spindles in which the poles are shared. Amorphic alleles
      result in pupal lethality and in mitotic arrest in which condensed chromosomes
      are arranged on circular monopolar spindles. The size of the single centrosomal
      body in these circular figures suggests that loss of function of the serine
      threonine protein kinase encoded by aur leads to a failure of the centrosomes to
      separate and form a bipolar spindle.

PMID- 7720078
TI  - The in vivo effects of neutralizing antibodies against IFN-gamma, IL-4, or IL-10
      on the humoral immune response in young and aged mice.
AB  - In the present study we investigated whether age-related changes in the
      composition and functional properties of murine CD4+ T cells are reflected in
      vivo by a changed humoral response to influenza vaccine in aged mice. After the
      primary immunization, the titers of influenza-specific IgM, IgG1, IgG2a, and
      IgG2b, but not of IgG3 and IgE, were significantly reduced in aged mice compared
      to young mice. Treatment of aged mice with anti-IFN-gamma, anti-IL-4, or anti-IL
      10 resulted in levels of IgM and IgG1 comparable to those found in young mice,
      whereas IgG2a and IgG2b were further decreased. After the booster immunization
      IgE was significantly enhanced in aged mice, whereas no differences were observed
      with regard to the other isotypes. During the primary response in young mice,
      anti-IFN-gamma stimulated IgG1 and IgE, whereas an inhibition of IgG2a, IgG2b,
      and IgG3 was observed. Anti-IL-4 caused a decrease only in IgG3 while anti-IL-10
      increased IgM and IgG1 and decreased IgG2b and IgG3. During the primary response
      in aged mice, all anti-cytokine antibodies enhanced IgM and IgG1 while IgE was
      only enhanced by anti-IL-10. By contrast, IgG3 was inhibited by anti-IFN-gamma
      and anti-IL-10. Anti-cytokine treatment of young mice increased all isotypes,
      except IgG3, in the secondary response, whereas the secondary response in aged
      mice was largely insensitive to anti-cytokine treatment. These data therefore
      support the idea that the in vivo effects of cytokines on isotype switching are
      dependent on the differentiation stage of B cells which may be different in young
      and aged mice.

PMID- 7720079
TI  - Utilization of soluble fusion proteins for induction of T cell proliferation.
AB  - A peptide display library was evaluated as a means to identify peptide binding
      motifs for class II molecules. Peptides expressed as part of a soluble fusion
      protein with a maltose binding protein (malE) were produced by Escherichia coli.
      Constructs containing the high-affinity binding influenza hemagglutinin peptide
      307W-319 (mal-HA) or the low-affinity binding tetanus toxoid peptide 830-843 (mal
      TT) were used as controls. mal-HA, but not mal-TT, inhibited synthetic
      biotinylated-HA peptide from binding to purified DR4 Dw4 molecules in a dose
      dependent manner. The fusion-peptide presentation system was also evaluated for
      its ability to induce antigen-specific T cell proliferation. DR4 Dw4+ B cells
      pulsed with mal-HA, but not mal-TT, induced dose-dependent proliferation of an HA
      specific DR4 Dw4-restricted T cell line to the same extent as synthetic HA
      peptide. Using this type of peptide display library, it may be possible to
      determine the antigenic specificity of T cell clones isolated from patients with
      autoimmune diseases.

PMID- 7720081
TI  - Functional characterization of the insulin-like growth factor I receptor on
      Jurkat T cells.
AB  - Insulin-like growth factor I (IGF-I) has been shown to be important in the
      maintenance, development, and proliferation of various types of leukocytes,
      particularly T cells. Radio-receptor binding assays demonstrate that Jurkat T
      cells bind 125I-IGF-I with an affinity of 1.77 nM (Kd) and express approximately
      230 receptors/cell. Specificity studies show insulin also binds the IGF-I
      receptor with an affinity 20-fold lower than that of IGF-I. Interaction of IGF-I
      with its receptor on Jurkat T cells induces the phosphorylation of tyrosine
      kinase which is detectable by Western blotting. The 95,000 MW protein detected is
      equivalent to the molecular weight of the beta chain of the IGF-I receptor
      described in other types of cells. These studies characterize the binding of IGF
      I to its receptor on Jurkat T cells, demonstrate that IGF-I binding induces
      tyrosine phosphorylation, and support the hypothesis that IGF-I is important in
      the induction of T cell activation.

PMID- 7720080
TI  - Irreversible inhibition of human natural killer cell natural cytotoxicity by
      modification of the extracellular membrane by the adenine nucleotide analog 5'-p
      (fluorosulfonyl)benzoyl adenosine.
AB  - Extracellular adenine nucleotides are inhibitors of the human natural killer cell
      line NK3.3 natural cytotoxicity activity. Natural cytotoxicity was inhibited
      approximately 26% by 1 mM ATP and 21% by 1 mM ADP. 5'-Adenylyl imidodiphosphate,
      a nonhydrolyzable ATP analog, inhibited natural cytotoxicity by 41% at a
      concentration of 1 mM and > 97% at a concentration of 10 mM. In contrast, AMP was
      not inhibitory. Adenosine was a weak inhibitor of natural cytotoxicity and may
      represent an alternate regulatory pathway. Removal of the nucleotides resulted in
      the restoration of control levels of natural cytotoxicity activity. The affinity
      label 5'-p-(fluorosulfonyl)benzoyladenosine (5'-FSBA) is a synthetic analog of
      ATP or ADP containing an electrophilic fluorosulfonyl group capable of covalently
      modifying proteins at adenine di- and triphosphate nucleotide-binding sites.
      Natural cytotoxicity was irreversibly inhibited by modification of the
      extracellular membrane of NK3.3 cells by 5'-FSBA. This inhibition was
      concentration dependent with an I50 approximately 100 microM and complete
      inhibition at 1 mM. Modification of NK3.3 by 5'-FSBA did not affect the formation
      of effector-target cell conjugates; however, granule release was inhibited. This
      targets the site of inhibition by 5'-FSBA modification to a pathway preceding
      granule release. Irreversible, covalent modification of surface adenine
      nucleotide-binding proteins by 5'-FSBA provides a probe to study the role of
      specific adenine nucleotide-binding proteins in the extracellular regulation of
      natural killer cytolytic activity by adenine nucleotides.

PMID- 7720082
TI  - In vitro generation of IFN-gamma-producing Listeria-specific T cells is dependent
      on IFN-gamma production by non-NK cells.
AB  - In vitro 5-day cultures of naive spleen cells with viable Listeria monocytogenes
      (VLM), but not heat-killed L. monocytogenes, induced CD4+ T cells that produced
      IFN-gamma upon secondary antigen stimulation. The VLM-induced Listeria-specific T
      cells produced IFN-gamma but lacked expression of IL-2 and IL-4. To study the
      role of IFN-gamma in the induction of the IFN-gamma-producing T cells, we added
      anti-IFN-gamma mAb to the primary culture and analyzed IFN-gamma production upon
      secondary antigen stimulation. Addition of anti-IFN-gamma mAb to the culture
      suppressed generation of IFN-gamma-producing CD4+ T cells, suggesting that IFN
      gamma is important in the induction of IFN-gamma-producing CD4+ T cells.
      Furthermore, our results showed that depletion of NK cells from spleen cells by
      anti-asialo GM1 antibody plus complement before culture enhanced induction of IFN
      gamma-producing CD4+ T cells. Although NK cells are known to produce IFN-gamma,
      the results indicate that NK cell-derived IFN-gamma may not be important in
      induction of the Listeria-specific IFN-gamma-producing CD4+ T cells in the
      culture system. In addition, we demonstrated that IFN-gamma expression was high
      in CD4+ T cells from cultures of spleen cells with VLM at the primary culture
      level. These results suggest that IFN-gamma derived from T cells may enhance
      production of IFN-gamma by CD4+ T cells, while NK cells rather suppress the
      induction of IFN-gamma producing CD4+ T cells.

PMID- 7720083
TI  - Studies on in vivo induction of HIV-1 envelope-specific cytotoxic T lymphocytes
      by synthetic peptides from the V3 loop region of HIV-1 IIIB gp 120.
AB  - We have previously reported the induction of MHC class I-restricted, CD8+
      cytotoxic T lymphocytes (CTLs) specific to human immunodeficiency virus type 1
      (HIV-1) in mice by a 15-amino acid peptide (R15K) from the V3 loop in gp120. We
      now present evidence showing that CTL activity induced by R15K was stable for 8
      10 weeks after a single injection and that as little as 20 micrograms peptide was
      sufficient for efficient CTL induction in vivo. While induction of CTLs was
      efficient with R15K emulsified in either complete or incomplete Freund's
      adjuvant, only a low-level CTL response was observed in mice immunized with R15K
      in either alum or saline. We analyzed a series of carrier-free synthetic peptides
      ranging in length from 8 to 24 amino acids from the V3 loop region and observed
      that peptide R10I consisting of 10 amino acids from the middle portion of R15K
      was more efficient for CTL induction. Additionally, lymph node cells from mice
      immunized with 24 and 15 amino acid peptides (N24G and R15K, respectively) when
      restimulated in vitro with R10I exhibited greater HIV-1 env-specific CTL activity
      than when either of the longer peptides was used for restimulation. A peptide
      consisting of only 8 amino acids (R8K) was sufficient neither for inducing
      primary CTLs nor for in vitro restimulation of lymph node CTL precursors. These
      results establish that a carrier-free 10-amino acid synthetic peptide from the V3
      loop region in HIV-1 gp120 has the optimal sequence for efficient induction of
      HIV env-specific CTLs in mice.

PMID- 7720084
TI  - Regulation of IFN-gamma and IL-10 synthesis in vivo, as well as continuous
      antigen exposure, is associated with tolerance to murine skin allografts.
AB  - C3H/HEJ mice are rendered hyporesponsive to multiple minor incompatible (B10.BR)
      skin allografts by pretreatment with irradiated B10.BR lymphoid cells injected
      via the portal vein, but not the lateral tail vein. As assessed by PCR with
      lymphocytes taken from grafted mice, or by measuring cytokines in vitro from
      antigen-restimulated cells, this hyporesponsiveness is associated with decreased
      mRNA for IFN-gamma and IL-2 production, but enhanced mRNA for IL-4 and IL-10
      production. In mice given B10.BR cells via the tail vein, but in addition
      injected every second day with anti-IFN-gamma antibody, similar enhanced graft
      survival (with diminished IFN-gamma/IL-2 and enhanced IL-4/IL-10 production) was
      seen. In a separate study spleen cells from pretreated mice were "parked" in
      lethally irradiated syngeneic mice for 21 days, along with B10.BR skin grafts to
      some of the recipients. Only when recipients received this reexposure to B10.BR
      antigen did adoptively transferred spleen cells show "persistence" of the ability
      to produce delayed graft rejection and preferential IL-4 production in vitro.

PMID- 7720086
TI  - IL-4-based helper activity of CD4+ T cells is radiation sensitive.
AB  - The capacity of CD4+ T cells to induce IgG synthesis in B cells has been known to
      be radioresistant for more than 20 years. However, the radiation sensitivity of
      helper T cells with regard to their ability to induce the synthesis of isotypes
      other than IgG has not been studied. We therefore irradiated KLH-primed lymph
      node T cells and examined their capacity to induce IgG, IgM, and IgE synthesis in
      hapten-primed B cells. We demonstrated that while the capacity of KLH-primed
      lymph node cells to induce IgG synthesis was not affected by irradiation, the
      capacity of such T cells to induce IgE synthesis was greatly reduced by gamma
      irradiation. This was consistent with our observations that IL-4 and IL-5
      synthesis in such cells was greatly diminished by irradiation, whereas IL-2
      synthesis was only minimally affected. A similar differential sensitivity to
      irradiation of the helper activity of Th1 and Th2 clones was observed with regard
      to their ability to induce IgE and IgG synthesis under cognate conditions.
      Irradiation greatly inhibited the capacity of Th2 clones to induce IgE synthesis,
      but only minimally affected the capacity of Th1 clones to induce IgG synthesis in
      primed B cells. The capacity of irradiated Th2 clones to induce IgE synthesis was
      restored by the addition of IL-4 and IL-5. These results taken together indicated
      that the sensitivity to irradiation of T helper cells with regard to the
      induction of IgE but not IgG synthesis was due to the sensitivity to irradiation
      of the production of IL-4 but not of IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720085
TI  - Induction of transcription factors in human T lymphocytes by aspirin-like drugs.
AB  - Aspirin-like drugs (ALD) induce calcium mobilization, an essential component of T
      cell activation, but do not induce the biosynthesis of IL-2. To understand the
      extent to which ALD may mimic mitogenic stimulation, we studied cytoplasmic and
      nuclear signaling steps in ALD-treated T cells. We found that ALD induce a
      transient activation of protein kinase (PKC) but have no effect (in comparison to
      anti-CD3 antibodies) on protein tyrosine phosphorylation nor on PCL gamma 1
      tyrosine phosphorylation. ALD-induced calcium mobilization and PKC activation are
      independent of tyrosine protein kinase activity as shown by the lack of effect of
      herbimycin, a tyrosine-protein kinase-specific inhibitor. Although we detected no
      IL-2 mRNA in ALD-treated cells, the nuclei of these cells contain proteins
      capable of binding to three regulatory sequences in the IL-2 promoter region:
      NFAT, NF kappa B, and AP-1. These binding activities are expressed only in
      activated T cells. The expression of AP-1 depended on calcium mobilization and
      PKC activation. These data suggest that ALD cause transient but significant
      changes in T cell transmembrane signaling, although some events induced by
      stimulation with anti-CD3 antibodies are not induced by ALD. The signal is
      transmitted to the nucleus and induces DNA-binding activity by several
      transcription factors. However, the ALD stimulus is not capable of causing
      complete T cell activation.

PMID- 7720087
TI  - Systemic treatment with interleukin-4 induces regression of pulmonary metastases
      in a murine renal cell carcinoma model.
AB  - Advanced metastatic renal cell carcinoma has been shown to be responsive to
      immunotherapy but the response rate is still limited. We have investigated the
      therapeutic potential of systemic interleukin-4 (IL-4) administration for the
      treatment of pulmonary metastases in the murine Renca renal adenocarcinoma model.
      Renca cells were injected iv in Balb/c mice to induce multiple pulmonary tumor
      nodules. From Day 5, Renca-bearing mice were treated with two daily injections of
      recombinant murine IL-4 for 5 consecutive days. IL-4 treatment induced a
      significant reduction in the number of lung metastases in a dose-dependent manner
      and significantly augmented the survival of treated animals. Immunohistochemistry
      studies, performed on lung sections, showed macrophage and CD8+ T cell
      infiltration in the tumor nodules 1 day after the end of IL-4 treatment. The CD8
      infiltration increased by Day 7 after IL-4 treatment. Granulocyte infiltration
      was not detectable. To clarify further the role of the immune system in IL-4 anti
      tumor effect, mice were depleted of lymphocyte subpopulations by in vivo
      injections of specific antibodies prior to treatment with IL-4. Depletion of CD8+
      T cells or AsGM1+ cells abrogated the effect of IL-4 on lung metastases, whereas
      depletion of CD4+ T cells had no impact. These data indicate that CD8+ T cells
      and AsGM1+ cells are involved in IL-4-induced regression of established renal
      cell carcinoma.

PMID- 7720090
TI  - Modulation of IL-4 production in murine spleen cells by prostaglandins.
AB  - Recently, it has been reported that IL-4 production by murine Th2 cell lines is
      insensitive to inhibition by E-type prostaglandins. In the present study, IL-4
      production in vitro by freshly isolated concanavalin A (Con A)-stimulated murine
      spleen cells was readily suppressed by PGE2 with an I50 of 2 nM. Comparable
      suppression by PGE2 was seen after priming by anti-CD3 epsilon antibody instead
      of Con A or with other changes in the culture conditions. PGE2 was an effective
      inhibitor after elimination of Ly2.2+ T cells, consistent with a direct effect on
      Th2 cells. In the absence of added prostaglandins, IL-4 production was enhanced
      1.5- to 7.0-fold by 0.2-2.0 microM indomethacin, indicating that endogenous
      arachidonate metabolites such as PGE2 and PGI2 regulate IL-4 production in our
      usual culture system. The inhibition of Th2 cell secretion by PGE2 in vitro may
      have physiologic and pharmacologic implications for the regulation of Th2 cell
      function and IgE production in vivo.

PMID- 7720088
TI  - Upregulation of interferon-induced indoleamine 2,3-dioxygenase in human
      macrophage cultures by lipopolysaccharide, muramyl tripeptide, and interleukin-1.
AB  - The tryptophan decyclizing enzyme indoleamine 2,3-dioxygenase (IDO) was induced
      in human monocyte-derived macrophages (MDM) treated with human recombinant
      interferon-beta (IFN-beta) or interferon-gamma (IFN-gamma). Treated cells
      exhibited dose-dependent increases in IDO when assayed 48 hr after treatment.
      Cells exposed to IFN-gamma were observed to exhibit consistently higher peak
      levels of IDO when compared with cells incubated in the presence of IFN-beta.
      When IFN-beta-treated cells were incubated in the presence of specified amounts
      of bacterial lipopolysaccharide (LPS) or liposome-encapsulated muramyl tripeptide
      (MTP), peak IDO activity increased such that enzyme activity was comparable to
      maximal activity observed with IFN-gamma-treated cells. LPS and MTP also
      upregulated IFN-gamma-mediated IDO activity when suboptimal amounts of IFN-gamma
      were used. When macrophages were costimulated with various concentrations of
      human recombinant interleukin 1 alpha (IL-1 alpha), along with either maximum
      stimulating amounts of IFN-beta or suboptimal amounts of IFN-gamma, IDO activity
      was upregulated in a manner similar to results obtained using the microbial
      products as stimuli. While neither IL-1 alpha or IL-1 beta was detected in
      culture supernatants from macrophages treated with either LPS or MTP (alone or in
      combination with IFN), IL-1 alpha was detected in cell lysates of macrophages
      treated with these upregulators. Although neutralizing antibody to IL-1 alpha
      abolished the upregulatory effect of exogenous IL-1 alpha, it had no effect on
      upregulation by LPS or MTP. This suggests that although LPS and MTP may induce
      production of cell-associated IL-1 alpha, upregulation of IDO activity by these
      agents is independent of IL-1 alpha production and may be mediated through
      distinct pathways.

PMID- 7720089
TI  - Polymorphonuclear neutrophils enhance suppressive activities of anti-CD3-induced
      CD4+ suppressor T cells.
AB  - We investigated the effects of polymorphonuclear neutrophils (PMN) on the
      suppressive activities of CD4+ suppressor T cells induced by immobilized mAb to
      the CD3 molecular complex in order to explore the role of PMN in the regulation
      of humoral immune responses. CD4+ T cells that had been treated with mitomycin C
      induced the IgM production from highly purified B cells in cultures stimulated
      with immobilized anti-CD3. Addition of CD4+ T cells that had not been treated
      with mitomycin C (control T4 cells) suppressed the IgM production induced by
      immobilized anti-CD3-stimulated T4 mito. PMN enhanced the degree of suppression
      of the IgM production by anti-CD3-stimulated control T4 cells. The capacity of
      PMN to enhance the suppressive activity of anti-CD3-stimulated control T4 cells
      was restored when PMN were fixed with paraformaldehyde (PFA), suggesting that
      direct interactions between PMN and CD4+ T cells, but not soluble factors
      secreted by PMN, were involved in the enhancement of suppression. Fresh PMN as
      well as PFA-fixed PMN enhanced the endogenous IL-2 production by immobilized anti
      CD3-stimulated CD4+ T cells. Moreover, neither fresh PMN nor PFA-fixed PMN
      significantly augmented the suppressive activity of anti-CD3-stimulated control
      T4 cells in the presence of exogenous IL-2. These results indicate that PMN
      enhance the suppressive activity of anti-CD3-stimulated control T4 cells through
      direct interactions between PMN and CD4+ T cells. The enhancement of the
      suppressive activity of CD4+ suppressor T cells by PMN is accounted for by the
      enhancement of the endogenous IL-2 production by anti-CD3-stimulated CD4+ T
      cells. Thus, the data demonstrate that PMN influence the magnitude of humoral
      immune responses by regulating the production of IL-2 through direct interactions
      with T cells.

PMID- 7720091
TI  - Stage-specific induction of terminal deoxynucleotidyl transferase in a T-lymphoid
      line upon coculture with a thymic stromal line.
AB  - We previously reported an in vitro T-cell differentiation system in which the L4
      lymphoid clone was cocultured with the St3 stromal line derived from the same
      murine thymic tumor, 15#4T.L4 cells in L4-St3 cocultures sequentially express Thy
      1 and CD4 in a manner typical of normal thymocytes. In contrast, L4 cells grown
      in medium alone retain their Thy-1-CD4- phenotype. We also isolated L4 subclones
      from the coculture with increasingly differentiated phenotypes with respect to
      Thy-1 and CD4. We now report induction of an additional thymocyte differentiation
      marker, terminal deoxynucleotidyl transferase (TdT) in 15#4T cells (and to a
      lesser extent subcloned L4 cells) upon coculture with St3 stroma. Coculture of
      15#4T cells with St3 stroma resulted in expression of TdT as measured by
      ribonuclease protection for TdT RNA and Western immunoblotting for TdT protein.
      Cocultured L4 cells were induced for TdT expression to a lesser degree and for a
      shorter period of time. The magnitude of TdT RNA induction was maximal for cell
      lines with the least mature differentiation phenotype (15#4T and L4: Thy-1-CD4-)
      and decreased proportionally for subclones with increasingly mature phenotype,
      e.g., L4E cells (Thy-1+CD4+). TdT protein was undetectable by Western
      immunoblotting and immunofluorescent staining of the L4E subclone on or off
      stroma. Recombination-activating gene-1 (RAG-1), which is expressed in immature
      thymocytes during T-cell receptor rearrangement, but suppressed in mature
      thymocytes, was also examined using the ribonuclease protection assay.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7720092
TI  - The upregulating effect of dexamethasone on tumor necrosis factor production is
      mediated by a nitric oxide-producing cytochrome P450.
AB  - Dexamethasone (DEX) is a well-known inhibitor of tumor necrosis factor (TNF)
      production when given shortly before lipopolysaccharide (LPS). However, DEX (10
      mg/kg, ip) potentiates TNF production when administered 24-48 hr before LPS (16
      micrograms/kg, ip). We have found that this is probably due to DEX induction of
      cytochrome P450 3A, which is known to produce nitric oxide (NO). The upregulating
      effect of DEX on TNF production is associated with increased NO production. Both
      the upregulation of NO and of TNF production by DEX are inhibited by co
      administration of the P450 3A inhibitor troleandomycin (TAO, 40 mg/kg, ip). These
      data suggest that P450 3A-generated NO might be involved in TNF induction.

PMID- 7720094
TI  - Flexural rigidity of echinoderm sperm flagella.
AB  - The stiffness (flexural rigidity) of live sperm flagella, Triton-demembranated
      flagella (axonemes), trypsin-digested axonemes, and doublet microtubules of the
      axonemes in echinoderms was determined from the relationship between their
      deformation when a stream of medium was applied and the viscous resistance of the
      medium acting on the flagellum. The stiffness of the flagellum beating in
      seawater was 5.8 x 10(-21) Nm2 for bending in the direction perpendicular to the
      beating plane and 4.2 x 10(-22) Nm2 for bending within the beating plane. A
      similar difference in stiffness from the difference in bending directions was
      found in reactivated flagella with 1 mM ATP. The stiffness of live flagella
      immobilized in CO2-saturated seawater and axonemes in ATP-free medium was similar
      to that of beating flagella for bending in the direction perpendicular to the
      beating plane. The stiffness of motionless flagella significantly decreased with
      erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and vanadate. The trypsin-digestion
      of motionless axonemes did not change their stiffness. The stiffness of doublet
      microtubules was 1.4 x 10(-23) Nm2 in 0.1 mM ATP medium and 6.1 x 10(-23) Nm2 in
      ATP-free medium. These results suggest that doublet pairs lying parallel to the
      beating plane of the flagellum retain fewer cross-bridges than doublet pairs
      lying perpendicular to the beating plane.

PMID- 7720093
TI  - High IL-4 production is a stable phenotype of CD8negCD45RAnegCD27neg T cells.
AB  - CD27neg T cells are found only among CD4pos-CD45ROpos T cells and represent a T
      cell subset functionally distinct from CD27pos T cells. We examined
      CD4posCD45ROpos T cells that were sorted into CD27neg and CD27pos populations for
      their cytokine production in response to different activation pathways. We found
      that CD27neg T cells are characterized by high IL-4 and low IL-2 production,
      regardless of whether the cells were activated through CD3 plus CD28, CD2 plus
      CD28, or PHA plus PMA. However, subpopulation-specific patterns of cytokines were
      the clearest demonstrable following CD2 plus CD28 stimulation. We conclude from
      these data that high IL-4 production is a stable phenotype of CD27neg T cells.

PMID- 7720095
TI  - Relationship between intracellular period modulation and external environment
      change in Physarum plasmodium.
AB  - The relationship between intracellular period modulation and external environment
      change was investigated from the viewpoint of internal information coding in
      Physarum plasmodium. For the external conditions, concentration changes of
      attractant (galactose) and repellent (KCl) were used, and the internal responses
      were measured as the thickness oscillation of the plasmodium. (i) Period of the
      intracellular oscillation decreased when the concentration of attractant was
      increased and when the concentration of repellent was decreased. (ii) The period
      increased when the attractant was decreased and when the repellent was increased.
      (iii) The larger concentration change induced the larger period modulation. (iv)
      These responses were observed when the change of concentration was greater than a
      threshold value. From these results, it was clarified that the relative change in
      environmental condition is encoded on the relative period modulation in
      intracellular oscillation. This means that the period change does not directly
      represent the environment itself but represents the change of its condition.
      Thus, it is further suggested that the plasmodium estimates the environmental
      condition based on the relationship between the previous external condition and
      the present one.

PMID- 7720096
TI  - Clarification of PC12 cell growth inhibition by a sialoglycopeptide from bovine
      brain under low serum condition.
AB  - To study the effect of a bovine brain sialoglycopeptide (SGP) on the nerve cell
      growth, PC12 cells were used as a model system. Though the inhibition of cell
      growth, measured by the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium
      bromide (MTT) assay, by SGP was slight under the serum concentration of 10%, it
      was clearly detected under that of 1 to 2%. For the preparation of SGP,
      filtration through a nitrocellulose membrane was useful.

PMID- 7720097
TI  - Nuclear phosphoinositide signalling enzyme in human B lymphoid cells.
AB  - The modulation of phosphoinositidase C (PIC) beta activity upon interferon
      treatment in Burkitt lymphoma cells (Daudi) and its localization and expression
      have been analyzed by Western blotting, immunocytochemical and
      immunoelectronmicroscopy analysis. Results have disclosed an early increase of
      phosphatidyl-inositol-bisphosphate (PIP2) hydrolysis at nuclear level upon
      interferon (IFN) treatment paralleled by the evidence of an increase of PIC beta
      1 expression. PIC beta 1 expression has been detected in the nuclear compartment
      also in a clone of Daudi cells selected for the resistance to the
      antiproliferative action of interferon alpha but no modulation of the enzyme has
      been detected upon interferon treatment. Since no changes in terms of PIP2
      hydrolysis have been found at nuclear level in this selected line, we suggest
      that the antiproliferative action of interferon on Burkitt lymphoma cells is
      mediated by a possible recruitment of nuclear PIC beta 1 expression.

PMID- 7720098
TI  - Local changes of medium in studies of individual cells.
AB  - A procedure is described for changing the medium surrounding individual cells
      attached to the bottom of a cell chamber. A small hole at the "apex" of a plastic
      U-tube allowed application and withdrawal of medium. The medium to be applied was
      perfused through the U-tube by pressure at one end and suction at the other. To
      prevent premature delivery of new medium from the U-tube, suction of the outlet
      dominated resulting in a net withdrawal of medium from the cell chamber. The flow
      of medium through the hole could be reversed rapidly by arresting the suction
      with an electromechanical valve. In this way it was possible to obtain 95%
      replacement of medium within 60 ms. A pressure transient arising from the closure
      of the valve was damped by the presence of a small air bubble in the system. To
      secure a precise deposition of medium and minimize the risk of mechanical
      disturbances to the cell it was essential to be able to inspect the medium
      changes visually. For this purpose the fluorescent indicator rhodamine B bound to
      dextran proved satisfactory. Free rhodamine B could not be used because it had
      biological effects, as was evident from studying ATP-regulated K+ channels in
      pancreatic beta-cells. When using a purpose-designed syringe pump for perfusing
      the U-tube, the technique allows well controlled exposure of individual cells to
      test substances added together with dextran-linked rhodamine B.

PMID- 7720099
TI  - Apoptosis by demecolcine in V79 cells.
AB  - Demecolcine (Colcemid), an inhibitor of spindle fiber formation in M phase,
      induced apoptosis in V79 cells. At a concentration of 0.01 microgram/ml
      demecolcine, V79 cells proliferated exponentially as well as controls, although
      temporal M phase accumulation occurred 6 h after the addition of demecolcine. At
      0.1 microgram/ml, the cells became hyperploid after remaining in the M phase for
      some time. Apoptosis occurred in V79 cells exposed to demecolcine at a
      concentration of 0.03 microgram/ml. Apoptosis was defined as the appearance of a
      sub-G1 peak in DNA histograms and a ladder pattern of fragmented DNA in
      gelelectrophoresis.

PMID- 7720100
TI  - Microtubule reorganization and lysosome redistribution by a viral v-src oncogene,
      in mouse Balb/3T3 cells expressing human EGF receptor.
AB  - The epidermal growth factor (EGF)-induced endocytosis of its receptor is an
      obligatory pathway for the cellular regulation of the EGF-specific receptor (EGF
      R). BNER4 is a mouse Balb/3T3 cell line transfected with human EGF-R
      complementary DNA (cDNA). B4/src-13 and B4/src-24 are BNER4 cells transfected
      with a viral oncogene v-src. Indirect immunofluorescence study demonstrated that
      EGF-R was mostly localized at the perinuclear region in BNER4 cells at 60 min
      after EGF addition, whereas it was diffusely distributed throughout the cytoplasm
      in its v-src transfectants. Double indirect immunofluorescence study further
      confirmed that EGF-R was localized in lysosomes in BNER4 and B4/src-13 cells at
      60 min after EGF addition. Intracellular distribution of the Golgi apparatus,
      clathrin-coated vesicles and early endosomes were similar in all cell lines.
      However, the lysosomes detected by anti-lysosomal membrane protein (LGP85)
      antibodies were diffusely distributed throughout the cytoplasm in the v-src
      transfectacts. By contrast, in the parental BNER4 cells, the lysosomes were
      mostly localized in the perinuclear region. The organization of microtubules, but
      not of actin, was markedly different between BNER4 cells and its v-src
      transfectants. Nocodazole, which depolymerizes microtubules, altered the
      distribution of the lysosomes and EGF-R in BNER4 cells. Both intracellular
      lysosome distribution and microtubule organization in nocodazole-treated BNER4
      cells were found to be similar to those in its v-src transfectants without
      nocodazole treatment. These findings support the notion that changes in lysosome
      distribution may be correlated with microtubule reorganization by v-src in mouse
      Balb/3T3 cells.

PMID- 7720101
TI  - The molecular biology of the flavin-containing monooxygenases of man.
AB  - cDNA clones encoding five distinct members of the FMO family of man (FMOs 1, 2,
      3, 4 and 5) were isolated by a combination of library screening and reverse
      transcription-polymerase chain reaction techniques. The deduced amino acid
      sequences of the human FMOs have 82-87% identity with their known orthologues in
      other mammal but only 51-57% similarity to each other. The hydropathy profiles of
      the proteins are very similar. From the calculated rate of evolution of FMOs (a
      1% change in sequence per 6 million years) it would appear that individual
      members of the FMO gene family arose by duplication of a common ancestral gene
      some 250-300 million years ago. Each of the FMO genes was mapped by the
      polymerase chain reaction to the long arm of human chromosome 1. The localization
      of the FMO1 gene was further refined to 1q23-q25 by in situ hybridization of
      human metaphase chromosomes. RNase protection assays demonstrated that in man
      each FMO gene displays a distinct developmental and tissue-specific pattern of
      expression. In the adult, FMO1 is expressed in kidney but not in liver, whereas
      in the foetus its mRNA is abundant in both organs. FMO3 expression is essentially
      restricted to the liver in the adult and the mRNA is either absent, or present in
      low amounts, in foetal tissues. FMO4 is expressed more constitutively. Human FMO1
      and FMO3 cDNAs were functionally expressed in prokaryotic and eukaryotic cells.
      FMO1 and FMO3, expressed in either system, displayed product stereoselectivity in
      their catalysis of the N-oxidation of the pro-chiral tertiary amines, N-ethyl-N
      methylaniline (EMA) and pargyline. Both enzymes were stereoselective with respect
      to the production of the (-)-S-enantiomer of EMA N-oxide. But in the case of
      pargyline, the enzymes displayed opposite stereoselectivity, FMO1 producing
      solely the (+)-enantiomer and FMO3 predominantly the (-)-enantiomer of the N
      oxide.

PMID- 7720102
TI  - Prochiral sulfides as in vitro probes for multiple forms of the flavin-containing
      monooxygenase.
AB  - A homologous series of alkyl-substituted p-tolyl sulfides have been synthesized
      and evaluated as in vitro, isozyme-selective substrate probes for the microsomal
      flavin containing monooxygenases. Straight-chain and branched-chain alkyl
      homologs were metabolized to the corresponding (R)- and (S)-sulfoxides which were
      analyzed by chiral phase high-performance liquid chromatography. Initial studies
      demonstrated that the stereochemical composition of alkyl p-tolyl sulfoxides
      generated by FMO2, purified from rabbit lung, was a function of the degree of
      steric crowding about the prochiral center. In contrast, purified rabbit liver
      FMO1 formed the (R)-sulfoxide from the n-alkyl series of substrates in a highly
      stereoselective manner (> 90%). Similar results were obtained with these two
      rabbit cDNAs expressed in E. coli. In contrast to rabbit FMO1 and FMO2, a
      characteristic feature of catalysis by cDNA-expressed rabbit FMO3 was the lack of
      stereoselectivity observed for formation of methyl p-tolyl sulfoxide.
      Collectively, these data demonstrate that the stereochemical composition of
      sulfoxides generated from the n-alkyl series of sulfides is isozyme-dependent.
      Metabolism of methyl p-tolyl sulfide by detergent-solubilized hepatic microsomes
      from a wide variety of experimental animals yielded predominantly (R)- methyl p
      tolyl sulfoxide, which, at least in rabbit liver, is indicative of catalysis
      dominated by FMO1. However, solubilized human and macaque liver preparations
      catalyzed this reaction in a relatively non-stereoselective manner. Macaque liver
      FMO was purified and the metabolite profile generated from the n-alkyl p-tolyl
      sulfides was found to be most similar to rabbit FMO3. Moreover, antibodies
      directed against macaque liver FMO selectively reacted with rabbit FMO3 and a
      microsomal protein expressed in adult human, but not fetal human liver, adult
      human kidney or adult human lung. Therefore, an FMO isoform expressed selectively
      in adult primate liver has catalytic and immunochemical properties consistent
      with its classification in the FMO3 family.

PMID- 7720103
TI  - Role of hepatic flavin-containing monooxygenase 3 in drug and chemical metabolism
      in adult humans.
AB  - In conjunction with asymmetric chemical syntheses and spectral, chiroptical,
      chromatographic and stereochemical correlation methods, we have developed
      procedures for the quantification of sulfoxide enantiomers and tertiary amine N
      oxide diastereomer metabolites arising from the action of the adult human liver
      and other flavin-containing monooxygenases (FMOs). The parallel nature of the
      metabolic in vitro-in vivo studies and the use of chemical model oxidation
      systems allowed us to identify the FMO isoform involved. We investigated the
      enantioselective S-monooxygenation of cimetidine and the diastereoselective
      tertiary amine N-1'-oxygenation of (S)-nicotine as stereoselective functional
      probes of adult human liver FMO action. In both cases, the majority of evidence
      points to adult human liver FMO3 as the principal enzyme responsible for
      cimetidine S-oxygenation and (S)-nicotine N-1'-oxygenation in vitro and in vivo.
      The excellent agreement between the absolute configuration of the major
      cimetidine S-oxide and (S)-nicotine N-1'-oxide metabolites isolated from human
      urine and the major metabolite formed in the presence of adult human liver
      microsomes suggests that in vitro hepatic preparations may serve as a useful
      model for the in vivo condition. Further, that adult human liver cDNA-expressed
      FMO3 in Escherichia coli also gave the same absolute stereoselectivity (i.e. for
      (S)-nicotine N-1'-oxygenation) confirms the identity of the monoxygenase in vivo.
      Although we cannot rule out the involvement of minor contributions of cytochrome
      P-450 monooxygenases in cimetidine and (S)-nicotine oxidation, the majority of
      the data support the fact that cimetidine S-oxygenation and (S)-nicotine N-1'
      oxygenation are stereoselective functional probes of adult human liver FMO3
      activity. Finally, because the stereochemistry of the principal metabolite of
      cimetidine and (S)-nicotine in small experimental animals is distinct from that
      observed in humans, it is likely that species variation in predominant FMO
      isoforms exist and this may have important consequences for the choice of
      experimental animals in human preclinical drug design and development programs.

PMID- 7720104
TI  - Potential role of the flavin-containing monooxygenases in the metabolism of
      endogenous compounds.
AB  - Several xenobiotics and their corresponding cysteine S-conjugates are metabolized
      in vivo to cysteine S-conjugate sulfoxides and/or N-acetylcysteine S-conjugate
      sulfoxides. Homocysteine S-conjugates, such as methionine and ethionine, are also
      metabolized in vivo to sulfoxides. The enzymatic basis for these metabolic
      reactions is not known. Recently, the rat liver and kidney S-benzyl-L-cysteine S
      oxidase activities were found to be associated with flavin-containing
      monooxygenases that are structurally and immunochemically related to known FMO1
      isoforms. Further evidence for FMO1 being the major FMO isoform involved in S
      benzyl-L-cysteine sulfoxidation was obtained from kinetic studies with cDNA
      expressed rabbit FMOs. Endogenous cysteine S-conjugates, e.g.
      cysteinylcatecholamines, cysteinylleukotrienes, lanthionine and djenkolic acid
      may also be substrates for FMOs, since S-benzyl-L-cysteine can be considered a
      model for these compounds. Methionine, an endogenous homocysteine S-conjugate,
      was shown to be a substrate for cDNA-expressed rabbit FMO1, FMO2, and FMO3,
      however, the methionine sulfoxidation reaction was preferentially catalyzed by
      FMO3. These results suggest that FMOs may also play a role in the in vivo
      metabolism of endogenous homocysteine S-conjugates.

PMID- 7720105
TI  - Multisubstrate flavin-containing monooxygenases: applications of mechanism to
      specificity.
AB  - Kinetic studies on mechanism of the flavin-containing monooxygenase (FMO1) from
      pig liver microsomes are described in detail with special emphasis on the
      interpretation of constants derived from the rate equation. The evidence reviewed
      indicates that oxidation of xenobiotic substrates by the 4a-hydroperoxyflavin
      form of the enzyme is a second order reaction not saturable by substrate. Under
      steady-state conditions decomposition of the hydroxyflavin (an intermediate form
      of the enzyme that does not require enzyme-substrate or enzyme-product
      equilibrium complexes) is rate limiting. The lack of detectable equilibrium
      binding is also consistent with rate constants defining Km deduced from steady
      state measurements. A model consistent with all evidence currently available
      indicates that at saturating concentrations of xenobiotic substrates that
      catalytic site on the enzyme is unoccupied most of the time. This property may
      explain why non-substrate analogs of xenobiotic substrates do not inhibit FMO
      activity. Rate constants for the oxidation of xenobiotics by the enzyme-bound and
      synthetic 4a-hydroperoxyflavin indicate that while enzyme protein accelerates the
      reaction with xenobiotics bearing nitrogen, it has only marginal effects on the
      oxidation of substrates bearing sulfur. Differences in the nucleophilicity of
      compounds bearing these heteroatoms may be primarily responsible but other, as
      yet undefined, factors may also contribute. In addition, analysis of rate
      constants affected by protonated lipophilic amines indicates that these
      allosteric effectors apparently modify enzyme structure so as to affect two or
      more rate constants and, depending on the nature and concentration of the
      xenobiotic substrate, protonated amines can either stimulate or inhibit catalytic
      activity.

PMID- 7720106
TI  - Developmental regulation of flavin-containing monooxygenase (FMO) isoforms 1 and
      2 in pregnant rabbit.
AB  - Mammalian flavin-containing monooxygenase (FMO, EC 1.14.13.8) metabolizes a vast
      number of structurally diverse xenobiotics containing a soft-nucleophile,
      typically a nitrogen or sulfur. FMO is not inducible by the classical cytochrome
      P450 (CYP) inducers, such as phenobarbital, polycyclic aromatic hydrocarbons,
      ethanol or macrolide antibiotics. Evidence does exist from a number of
      laboratories, however, for developmental and hormonal regulation of FMO. Our
      laboratory has confirmed previous observations of enhanced FMO activity during
      mid- and late-gestation in maternal rabbit lung and have demonstrated that this
      response is due to increased protein and catalytic activity associated with FMO2.
      The time course of expression of FMO2 during mid- and late-gestation correlates
      to plasma peaks of progesterone or cortisol. FMO2 also peaks at parturition in
      maternal kidney, coincident with plasma cortisol levels. FMO2 is induced by s.c.
      administration of either progesterone or dexamethasone in lung, or by
      dexamethasone in kidney. Correlation of plasma progesterone or cortisol levels
      during gestation and postpartum support a role for progesterone, but not cortisol
      in regulation of FMO2 in maternal rabbit lung. The levels of FMO1 also appear to
      be increased during mid- and late-gestation in liver. FMO1 in liver may also be
      regulated during gestation by progesterone or glucocorticoids as administration
      of these steroids enhanced FMO1 mRNA levels 4-fold.

PMID- 7720107
TI  - [Raising the level of pathological diagnosis and prognosis of breast carcinoma].

PMID- 7720108
TI  - [Detection of point mutation of p53 gene by non-isotopic PCR-SSCP in paraffin
      embedded breast cancer tissue].
AB  - Non-isotopic PCR-SSCP method was used to detect point mutation of p53 gene in
      paraffin-embedded breast cancers. The abnormal shifting of the single-stranded
      DNA (ssDNA) was identified in 14 out of 60 cases. The point mutations of four
      cases were found in exons 5-6, three in exon 7 and seven in exon 8. The mutant
      p53 protein was detected by immunohistochemistry. The positive nuclear staining
      was observed in 13 cases, among which 11 cases showed abnormal shifting of ssDNA
      in SSCP analysis. The point mutations of the other two cases might occur in the
      regions which were not examined in this study. The point mutations of p53 were
      found in 5 cases in the absence of detectable protein. This probably resulted
      from the reduction or loss of antigenicity of p53 in some of the routinely
      processed tissues. Our results indicate that detection of point mutations of p53
      gene by PCR-SSCP method is more accurate and reliable than that by
      immunohistochemistry and non-isotopic PCR-SSCP is especially useful in the
      screening of point mutations during handling a large number of samples.

PMID- 7720109
TI  - [Quantitative study of P53 gene protein expression in the benign disease and
      cancer of breast].
AB  - P53 gene protein expression in breast benign disease and cancer was studied
      quantitatively using flow cytometry and cellular immunofluorescence staining
      technique. The results showed that P53 positive expression rate and content were
      lower in the benign disease of breast than that of the breast cancer. The content
      of P53 protein expression was also associated with the DNA ploidy in breast
      cancer. The content of P53 protein expression was higher in tumors with aneuploid
      cells than those with the diploid ones. The five year survival rate were also
      lower in P53 protein expression positive cases than the P53 negative one's.

PMID- 7720110
TI  - [Sequence analysis of N--ras and p53 gene mutation in the human lung
      adenocarcinoma cell lines].
AB  - Gene mutation and abnormal expression of ras oncogenes and p53 gene have a direct
      bearing on the carcinogenesis. Polymerase chain reaction (PCR), sequencing
      technique of ds DNA cycle and sequencing system were used to detect the gene
      mutation of N-ras as well as the exon 5 and 7 of p53 gene in hLA and LTEP-a2 cell
      lines of human lung adenocarcinoma. The result showed that mutation of both cell
      lines occurred on the 154th codon in exon5 of p53 gene, where GGC was displaced
      by GTC resulting a substitution of Val for Gly, nevertheless, N-ras oncogene and
      the exon7 of p53 gene are normal.

PMID- 7720111
TI  - [Light and electron microscopic histochemical studies of alkaline phosphatase
      (ALP) isoenzymes in gastric cancer].
AB  - By using light and electron microscopic histochemical techniques, the activities
      and distributions of ALP isoenzymes in gastric cancers and benign gastric
      diseases were examined. The results showed: Nagao, Regan and Kasahara isoenzymes,
      which were not expressed in normal gastric mucosae and non-malignant lesions, may
      be considered as the tumor markers of gastric cancer. The epithelium of
      intestinal metaplasia exhibited intestinal-type ALP only, which was one of the
      markers of well-differentiated intestinal metaplasia. In the view-point of the
      gene expression of ALP isoenzymes, two mutation hypothesis and recessive-gene
      mutation hypothesis may be proper for gastric cancer.

PMID- 7720112
TI  - [Electron microscopic studies of the endoplasmic reticulum in whole--mount
      cultured human nasopharyngeal carcinoma cell line].
AB  - The endoplasmic reticulum system (ER) in whole-mount human nasopharyngeal
      carcinoma parent cell line (CNE-2Z) and its variants L2, H2, L4 was observed
      using potassium permangnate as a fixtive. In lamellapodia and labopodia, the ER
      was arranged as a nest structure, but it usually formed lines of straight tubules
      in the filopodia. The results suggested that there may be some relationship
      between the ER and the functional activities of pseudopodia. No significant
      difference of ER was found yet in morphology, structure, quantities and
      distribution between CNE-2Z cells and its variants.

PMID- 7720113
TI  - [The inhibition effect of retinoic acid on the invasion and metastasis abilities
      of metastatic human lung cancer cell subline].
AB  - Pre-treatment of metastatic human lung cancer cell subline (PGCL3) with all trans
      retinoic acid (RA) resulted in inhibition of cell growth in vitro and invasion
      through the reconstituted basement membrane. RA was also noticed to inhibit the
      experimental metastatic ability of PGCL3. Data showed that 5/6, 3/6 and 2/6 of
      the nude mice developed lung colonization in the control, the 5 mumol/L and the
      10 mumol/L RA treated PGCL3 cells respectively. Data from DNA-RNA dot blot
      hybridization further showed that the 10 mumol/L RA treated cells expressed high
      levels of the human tissue inhibitors of metalloproteinases (Timp-1 and Timp-2)
      in comparing to the untreated cells. These results may help to clarify the
      mechanism of RA-induced inhibition effect on tumor invasion and metastasis.

PMID- 7720114
TI  - [Pathological study on thoracic carcinoids accompanied with Cushing's syndrome].
AB  - Eight patients with carcinoid tumors (5 from the lungs and 3 from the thymus)
      associated with Cushing's syndrome were studied. Among them, 5 were male and 3
      female with a mean age of 32.5 years. Histologically, all were typical
      carcinoids. Immunohistochemically, tumor cells were strongly positive of NSE,
      chromogranin A and ACTH in all 8 cases. Some tumors also positive for S-100,
      calcitonin, HCG alpha and HCG beta. Various amounts of neurosecretory granules
      were found in the tumors by electron microscopy and ACTH positive dots were also
      noticed in some of the neurosecretory granules in the tumor cells by
      immunoelectron microscopical colloidal gold labelling technique. By in situ
      hybridization technique, overexpression of chromogranin A mRNA was detected in
      all of the tumors reported.

PMID- 7720115
TI  - [The immune reconstitution in Scid mice and the effect of T, B, NK cells on the
      growth potential of CNE-2Z-H5 transplanted tumor].
AB  - CNE-2Z-H5 was transplanted into the Scid mice of which immune system was
      reconstituted with the peripheral lymphocytes or thymus of the isogenetic mice
      and the BALB/c nude mice of which NK cells were inhibited with cyclophosphamide.
      The results showed that the growth speed and weight of the tumors were in order
      from high to low among groups of Scid mice, BALB/c nude mice with NK inhibited,
      BALB/c nude mice, Scid mice with immune reconstitution. The transplanted tumor,
      in 6/6 cases injected beforehand with peripheral lymphocytes and 1/3 case
      transplanted accompanied with thymus disappeared within 22 days. The conclusion
      is that the immune reconstitution of Scid mice has succeeded and play an
      effective role in antitumor response.

PMID- 7720116
TI  - [Pathological and immunohistochemical study on anorectal melanoma].
AB  - Forty two cases of anorectal melanoma were studied which constituted 1.19% of all
      the anorectal malignancies collected in this series. 90% of the tumors located
      near by the dentate line. Grossly, the masses were nodular, fungiform or
      ulcerated. Histologically, pleomorphic tumor cells mixed together giving a
      feature somewhat like either carcinomatoid or sarcomatoid, with a predominance of
      one kind of the malignant cells. Histopathologic observation supported the idea
      that this tumor developed from the melanocytes and nevus cells located at the
      basal layer of the epithelium. Immunohistochemistry proved that melanocytes
      originated from the neural crest. S-100 protein was marker with high sensitivity
      but the specificity not ideal, so that, varied markers are recommended in order
      to improve the accuracy of diagnosis.

PMID- 7720117
TI  - [Electron microscopic study on the petechial hemorrhagic spots in patients with
      epidemic hemorrhage fever (EHF)].
AB  - EHF viral particles were found in the squamous epithelial cells and capillary
      endothelial cells of the petechial spots located at the mucous membrane of the
      soft palate in cases of early stage of severe type EHF by transmission electron
      microscopy. The viral particles are round or oval in shape, about 100 nm in
      diameter with a lipid bilayer envelope from which spikes are protruding. The
      virions matured by budding through the intracytoplasmic membranes into the smooth
      surfaced vesicles. The morphological characteristics of the virion coincided with
      the viral particles of Family Bunyaviridae. It was the first time to demonstrate
      that the squamous epithelial cells of the soft palate is one of the target cells
      in EHF virus infection and to describe the subcellular morphological evidence of
      the petechial spots at the soft palate by EM.

PMID- 7720119
TI  - [New types of ovarian neoplasms].

PMID- 7720118
TI  - [Clinical and experimental study of diagnosis of viral myocarditis using gene
      amplification by polymerase chain reaction].
AB  - Polymerase chain reaction (PCR) technique was applied for detection of
      picornavirus genomes in blood and myocardial tissue of patients with viral
      myocarditis. Additionally, the blood and myocardial tissue of rabbits infected by
      picornavirus was also screened by PCR. Twelve rabbits infected by piocrnavirus
      showed pathological change of myocarditis and all of these animals gave a
      positive PCR result for picornaviral RNA sequences in the blood and myocardial
      tissue. All 6 control rabbits gave no PCR positive signals. PCR gene
      amplification actually provides a new diagnostic approach to patients suspected
      of viral myocarditis.

PMID- 7720120
TI  - [A study of occupational asthma and specific IgE in sericulture workers].
AB  - Clinical investigation revealed that 75.6% (68/90) of sericulture workers
      examined had allergic respiratory symptoms. Of the 90 workers, 14 (15.6%)
      suffered from occupational asthma. Work-related allergens including silkworm
      cocoon (SC), silkworm urine (SU), moth excrete (ME) and moth scales (MS) were
      collected and prepared. Serum specific IgE levels were detected by ELISA. The
      results showed that the level of sIgE in asthmatic workers was significantly
      higher than that in the "common symptom" group, asymptomatic group and control
      group. No significant difference in total IgE was found between the workers and
      controls. The anti-SU-sIgE positive rate was significantly higher than those of
      sIgE to the other three allergens. These results indicate that the high levels of
      sIgE are responsible for occupational asthma in sericulture workers and that SU
      is an important allergen in these patients.

PMID- 7720121
TI  - [Biodistribution of monoclonal antibody and Fab fragment and antitumor effect of
      their conjugates on hepatoma xenografts].
AB  - McAb 3A5, a rat monoclonal antibody directed against human hepatoma cells, and
      its Fab fragment were compared on their biodistribution and the therapeutic
      effects of their conjugates linked to C1027, a highly potent antitumor
      antibiotic, on the growth of human hepatoma xenografts in nude mice.
      Biodistribution study with 125I-labeled McAb 3A5 and its Fab fragment in hepatoma
      bearing nude mice revealed that ID%/g values of McAb 3A5 were higher than those
      of the Fab fragment in tumor, liver, spleen and kidney; however, the T/NT ratios
      of Fab were higher than those of McAb 3A5. Imaging study with 131I-3A5 and 131I
      Fab showed that clear images of the tumor emerged 12h after injection of Fab and
      40 h after that of McAb 3A5. IC50 values for McAb-C1027 and Fab-C1027 were 4.2 x
      10(-14) mol/L, 8.6 x 10(-16) mol/L, respectively. Fab-C1027 conjugate was 49-fold
      more potent than McAb-C1027. Therapeutic effect of the conjugates was evaluated
      with hepatoma xenograft in nude mice. When treatment started 3 days after sc
      transplantation of the tumor with equivalent dose of C1027, 0.15 mg/kg, i.v., x3,
      tumor inhibition rates for McAb-C1027 and Fab-C1027 conjugates were 68% and 66%,
      respectively. When the treatment started on day 10 after transplantation with
      0.10 mg/kg, i.v., x6, tumor inhibition rates for McAb-C1027 and Fab-C1027
      conjugates were 24% and 54%, respectively. The results showed that compared with
      the intact McAb, Fab fragment displays higher specificity in biodistribution and
      exerts stronger inhibitory effect on the growth of established tumor xenografts.

PMID- 7720122
TI  - [Amplification, cloning and sequencing of beta nerve growth factor gene in the
      Chinese population].
AB  - Genomic DNA was extracted from white blood cells. Using the genomic DNA as
      template, the gene encoding nerve growth factor (beta-NGF) in the Chinese
      population was amplified using polymerase chain reaction (PCR). The beta-NGF gene
      obtained by PCR was then cloned into plasmid pUC 12 which was digested with SmaI.
      After transformation, screening and identification, 8 clones containing the beta
      NGF gene were analyzed. Nucleotide sequence of the NGF was determined by dideoxy
      nucleotide chain-termination method. The sequencing result showed that there are
      6 differences between the beta-NGF sequence of the Chinese population and
      previous reported beta-NGF sequence.

PMID- 7720123
TI  - [Fine needle aspiration cytology and influencing factors in breast cancer].
AB  - The results of 200 women with primary breast cancer who had fine needle
      aspiration cytology prior to definitive surgery at the Peking Union Medical
      College Hospital were presented. Among them, aspiration cytology was positive and
      suspicious in 87% (174/200) and pseudonegative in 13% (26/200). Clinical factors
      relating to the success of these aspiration were evaluated. The most significant
      factor was which physician performed the aspiration. Size of the lesion and type
      of the cancer were also important influences on the aspiration. Experiences in
      aspiration cytology were introduced by author.

PMID- 7720124
TI  - [Study of histopathological and ultrastructural differences between condylomata
      acuminata and pseudocondyloma of vulvae].
AB  - Histopathological alterations of condylomata acuminata were characterized by
      hyperkeratosis, parakeratosis, acanthosis, elongation of the rete ridges,
      pseudoepitheliomatous hyperplasia, discrete or grouped koilocytes, proliferation
      and dilatation of dermal capillaries, lymphocytic and histocytic infiltration
      around dermal capillaries. Histopathological pattern of pseudocondyloma of vulvae
      were characterized by finger-shaped configuration, epithelium was similar to
      normal of mucous membrane without atypia. The lesion was composed of a rich
      vascular network surrounded by connective tissue and a mild lymphocytic
      infiltration. Ultrastructural alterations of condylomata acuminata were
      characterized by proliferation of basal cells, enlarged and swollen nuclei in all
      layers, 1-4 large nucleoli, 1-3 nuclear bodies, interchromatin granules and
      perichromatin granules in some proliferating nuclei, swollen mitochondria,
      dilated endoplasmic reticulum, and dissolved glycogen. Ultrastructural
      alterations of pseudocondyloma of vulvae were characterized by proliferation of
      mucomembranous epithelial cells, mild swollen nuclei, 1-2 nucleoli, no nuclear
      body interchromatin and perichromatin granule, the dilatation of interstitial
      capillaries, and abundant fibril bundles in the dermis. Thus, the
      histopathological and ultrastructural manifestations of condylomata acuminata and
      pseudocondyloma of vulvae were significantly different. It may be of help in
      differentiation between the two disease.

PMID- 7720125
TI  - [An approach for PCR amplification of long DNA fragments].
AB  - The polymerase chain reaction (PCR) technique, evolved as a standard laboratory
      technique, has a major limitation: its inability to efficiently amplify fragments
      higher than 1.5 kb. In this paper, PCR conditions allowing the efficient
      amplification of long DNA fragments, especially a new proper buffer system, have
      been developed. The difference between the new PCR reaction buffer system and
      standard reaction system is that no KCl is included in the former. The results
      indicated that specificity and reproducibility for amplifying long DNA fragments
      by using new buffer system are satisfactory.

PMID- 7720126
TI  - [Effects of tripchlorolide (T4) of Tripterygium wilfordii Hook on the
      proliferation of peripheral blood mononuclear cells of rheumatoid arthritis
      patients].
AB  - Tripchlorolide (T4) is a single active ingredient recently isolated from
      Tripterygium wilfordii Hook. The effects of T4 on the proliferation of peripheral
      blood mononuclear cells (PBMC) of rheumatoid arthritis (RA) patients and normal
      subjects were studied, RA patients and sex- and age-matched normal subjects (each
      8 cases) were selected. PBMC were incubated with T4 of various doses (10, 20, 30
      and 40 ng/ml) in the presence or absence of PHA for 72 hours. The results were as
      follows: T4 remarkably inhibited the proliferation of both PHA-stimulated and
      unstimulated PBMC of normal subjects and PHA-stimulated PBMC of RA patients as
      measured by MTT colormetric method. However, T4 showed a biphasic reaction in
      unstimulated PBMC of 3 RA patients. These results indicates that T4 would be
      useful in the therapy of RA. The significance of biphasic reaction occurring in
      RA patients needs to be further investigated.

PMID- 7720127
TI  - [The effect of acute pulmonary alveolar hypoxia on canine plasma endothelin-1
      levels].
AB  - The effect of acute pulmonary alveolar hypoxia on plasma endothelin (ET)-1 levels
      was observed in 10 anesthetized dogs (hypoxic group). Plasma ET-1 like
      immunoreactivity (-LI) levels increased significantly at the fifth, fifteenth,
      sixtieth minute after hypoxia (fractional inspiratory O2 concentration 10%), but
      they had no remarkable change at the thirtieth minute. It was suggested that the
      first peak of ET-1-LI levels (the fifth minute) might be caused by the release of
      endothelin-1 which was formed before hypoxia and the second peak could be
      associated with the secretion of ET-1 after hypoxia. The effect of ligustrazine
      on plasma ET-1-LI levels during hypoxia was also investigated in other 8
      anesthetized dogs. Plasma ET-1-LI levels reduced significantly at the fifth
      minute after the injection of ligustrazine, compared with the hypoxic group. The
      result demonstrated that ligustrazine can inhibit the release of ET-1, which
      could be correlated with the blockade of calcium channel caused by ligustrazine.

PMID- 7720128
TI  - [Construction of the mammalian expression systems in hepatoma and non-liver cells
      with rat CPSI cDNA fragments].
AB  - Studies on recombination of 0.587 kb and 0.712 kb CPSI cDNA fragments with pSV2
      vecter and recombinant pSV2-CPS505 and pSV2-CPS507 plasmid expression of CPSI in
      non-liver culture cells were presented. The results confirmed that the NIH/3T3
      and 7402 hepatoma culture cells transfected individually with pSV2-CPS505 and
      pSV2-CPS507 plasmid were able to express CPSI effectively. The non-translational
      sequence is not indispensible to the highly tissue specific expression of CPS I.
      The studies provided experimental evidence and a cellular model for expression of
      novel CPSI in vitro, which has a great significance for carcinogenesis and
      differentiation.

PMID- 7720129
TI  - [Human parathyroid allotransplantation: comparison of donor grafts].
AB  - The authors compared the degrees of cell maturity, antigenicity and secretory
      function of parathyroid (PTG) tissues from cadavers (C-PTG), 20-28 wk fetus (F
      PTG) and PTG adenoma (A-PTG). In A-PTG tissues, clustered or scattered immature
      cells were observed, but there were none in F-PTG and C-PTG. C-PTG and A-PTG
      tissues revealed better secretory function than F-PTG. No clear difference was
      found in HLA class I (ABC) antigen quantity among the three donor PTG tissues,
      but the amount of HLA class II (DR) antigen in A-PTG and F-PTG were significantly
      lower than that in C-PTG. The results demonstrate that C-PTG, with better
      function, and F-PTG, with lower antigenicity, can be used in clinical
      transplantation. A-PTG is not suitable for clinical transplantation due to their
      immaturity and possibility of carcinomatous change.

PMID- 7720130
TI  - [Evaluation of two glycolipids from M. tuberculosis in the serodiagnosis of
      tuberculosis].
AB  - Sera from 112 healthy controls and 120 pulmonary tuberculous patients (61
      untreated patients and 59 active patients) were assayed, by ELISA, to test the
      activity of IgG and IgM antibodies against antigen of 2, 3-diacyl-trehalose-2'
      sulphate (SL IV) a phenolglycolipid antigen (PGLTb1) and purified protein
      derivative (PPD) from M. tuberculosis. Respectively, for SL IV-IgG-ELISA, SL IV
      IgM-ELISA, PGLTb1-IgG-ELISA, PGLTb1-IgM-ELISA, PPD-IgG-ELISA, the specificities
      were of 96.43, 96.43, 96.43, 96.43 and 95.53%; the sensitivities were of 51.67,
      32.50, 14.17, 18.33 and 33.33%; the efficiencies were of 73.28, 63.36, 53.88,
      56.03 and 62.93%; the predictive values for a positive result were of 96.87,
      86.67, 80.95, 84.62 and 88.64%. Among the three antigens tested, SL IV was found
      to be better than PGLTb1 and PPD.

PMID- 7720131
TI  - [Modified en bloc resection procedure for malignant tumor of the shoulder
      girdle].
AB  - En bloc resection of the shoulder girdle (Tikhoff-Linberg procedure) is a
      valuable limb-sparing surgical technique for bony and soft tissue malignant tumor
      in and around the proximal humerus and shoulder girdle. Significant amount of
      hand-elbow function is maintained with the procedure, and long time results in
      the treatment of neoplasms by this technique was found to be the same as by the
      method of a forequarter amputation or the shoulder disarticulation in the English
      literature. Four cases with malignant tumor in the shoulder girdle was treated
      with this modified method in our department. The average follow-up was 8 years.
      One case died due to another kind of tumor 6 years after operation, and other 3
      cases are alive and disease free.

PMID- 7720132
TI  - [Relation between age of mice and activity and characteristics of serum alkaline
      phosphatase].
AB  - Characteristics of serum alkaline phosphatase (SAP) were investigated in five
      strains of young and old mice (C57BL/6, BALB/c, C3H/Bi, MRL/Ipr, Ipr, NZB). SAP
      activity was measured and SAP kinetics was automatically measured by a
      spectrophotometer. The heat stability and the inhibitor, beta-bromotetramisole,
      sensitivity of SAP were also determined. Activity of SAP in old mice was
      significantly lower compared to young mice of the same strain (P < 0.01). SAP of
      young mice was more heat labile and was more sensitive to inhibitor as compared
      to SAP of old mice.

PMID- 7720133
TI  - [IL-1 beta mRNA expression in patients with rheumatoid arthritis].
AB  - Using arthroscopy techniques, 6 synovia samples from patients with rheumatic
      diseases were obtained. Of these, 2 patients had rheumatoid arthritis (RA), 2 had
      meniscus damage (MD), 1 had osteoarthritis (OA), and 1 had osteochondritis (OC).
      Using the guanidinium isothiocyanate method, total RNA from synovia was
      extracted, and 18S and 28S sedimentation bands (rRNA) were separated by
      electrophoresis. Plasmid containing the 1.3kb cDNA of IL-1 beta were extracted
      from E. coli by alkaline lysis. Subsequent digestion with XHO1 and then
      separation on gel isolated the 1.3kb cDNA for use as a probe. The probe was then
      labeled with 32P-dATP by nicktranslation and hybridized to the synovial RNA
      extract. The autoradiograph showed that in 4 cases of non-RA, the IL-1 beta cDNA
      did not hybridize to the synovial mRNA extract. An intense hybridization band was
      visible for mRNA from one RA case. The clinical and laboratory parameters and X
      rays of both knees and wrists of this case were all abnormal, and a rthroscopic
      findings showed pathological rheumatoid changes of synovium. In addition, this
      patient did not receive any DMARDs treatment for the RA. The other RA case did
      not have any hybridization bands. However, this patient did receive DMARDs
      treatment, and the RA went into remission. The Northern blot result above
      suggests that IL-1 beta mRNA expression in synovia is negative in non-RA cases
      and in cases where RA is in remission after DMARDs treatment. In the case with
      clinically active RA, IL-1 beta is highly expressed, as evidenced by the intense
      hybridization band.

PMID- 7720134
TI  - [A clinical analysis of cutaneous type dermatomyositis].
AB  - This paper reports nine patients with the classic cutaneous findings of
      dermatomyositis who did not develop clinical or laboratory evidence of muscle
      disease for at least 2 years after onset of their skin manifestations. Such
      patients represent 3.5% of our total experience with dermatomyositis patients
      during a 12 years period. None of the patients had evidence of malignancy. Each
      of five patients treated with oral prednisone for their cutaneous lesion or mild
      myositis after onset of their skin manifestations 3-12 years and had marked
      improvement. The author emphasizes that the cutaneous manifestations of
      dermatomyositis are pathognomonic of this disease and the term of this disease
      proposes cutaneous type dermatomyositis better than amyopathic dermatomyositis.

PMID- 7720135
TI  - [A primary evaluation of VAS for use in clinical experimental pain assessment].
AB  - The visual analogue scale (VAS) is a commonly used method for pain measurement
      abroad, though its clinical use has not been reported in our country. Fifty
      patients, who had received lower abdomen and lower extremities stimulation, were
      studied. Pain was induced by hand needle and electric needle stimulation. The
      data demonstrated that VAS is reliable and precise, that electric needle
      stimulation is more sensitive than hand needle stimulation, and that the factors
      of age, profession and education level affect the measured value of pain.

PMID- 7720136
TI  - [Association of polymorphism for HLA-DQA1 promotor region (QAP) with IDDM].
AB  - We have identified the DNA polymorphism for the HLA-DQA1 promotor region (QAP) in
      patients with early and late onset insulin-dependent diabetes mellitus (IDDM) by
      PCR direct sequencing. The result showed that single nucleotide substitution at
      position-92(C-->T-92) and -146 (T-->C-146) were detected in QAP for early and
      late onset IDDM respectively. These findings suggests that the mutation seems to
      alter the conformation of QAP so that these are likely to influence the aberrant
      expression of MHC-class II loci in beta-pancreatic islet cells.

PMID- 7720137
TI  - [An experimental study of the auditory brainstem implant in guinea pigs].
AB  - In order to examine the characteristics of the auditory brainstem implant, an
      animal model with electrical stimulation of the cochlear nucleus in guinea pigs
      was created. Middle latency response (MLR) to pulsatile electrical stimulation of
      the cochlear nucleus was recorded from the auditory cortex with bipolar
      plantinumiridium electrodes and stereotaxic technique. The electrically and
      acoustically generated MLRs have a similar morphology though there are little
      differences in the latencies, wave intervals and dynamic ranges. The results
      indicated that the central auditory pathways can be activated by means of
      electrical stimulation. The safety of the brain tissue to the electrical
      stimulation are also discussed.

PMID- 7720138
TI  - [Retroviral-mediated transfer of human beta-globin gene and its enhancer into MEL
      cells].
AB  - The present result showed that human beta-globin gene has been integrated into
      amphotropic packaging cell line PA317 in 5/13 clones of PA317 beta and 1/14 clone
      of PA317 beta E0.4. Retrovirus titers of amphotropic recombinant retrovirus
      ranged from 10(3) to 10(4) CFU/ml. MEL cells were transfected by supernant of
      PA317 beta and PA317 beta E0.4. Northern blot showed that the expression of human
      beta-globin gene in MEL beta E0.4 was significantly higher than MEL beta in mRNA
      level. This result indicated that an enhancer which comes from HS II of human LCR
      can increase human beta-globin gene mRNA expression in transfected MEL. However,
      the retrovirus titers of PA317 beta and PA317 beta E0.4 in our experiment were
      low. When large fragment enhancer (0.4 kb) was inserted into retrovirus vector,
      it could bring about the human beta-globin gene deletion in amphotropic packing
      cells.

PMID- 7720139
TI  - [The reversing effect of 4-hydroxycarbophenyl retiamide (R II) on the malignant
      phenotype of mouse forestomach carcinoma (MFC) cell line and the mechanism of its
      action].
AB  - 4-hydroxycarbophenyl retiamide (R II) is a new synthetic analogue of retinol, but
      with lower toxicity than retinoic acid. We studied its induction effects and its
      effects on some malignant phenotypes of the MFC cell line. The mechanism of these
      effects was also explored. MFC cells were grown in complete RPMI 1640 medium
      supplemented with 10(-5) mol/L R II for five passages. By then the cell growth
      rate slowed down; the rate of 3H-TdR incorporation and the colony-forming
      capacity of MFC cells decreased; morphologically, the cells became epithelial
      rather than fibroblastic with various degrees of polarization. Further
      investigation about the mechanism of these changes was also undergone. First by
      flow cytometry, it was shown that the R II-treated cells were retained in G1
      phase. Second, dot blot hybridization showed a decrease of more than 61% of c-myc
      mRNA and an increase of more than 52% of v-fos mRNA. The major chromosome
      distribution changed from 54-56 to 46-54 with an increase in diploid. Scanning
      microscopic examination showed that the R II-treated cells were covered by
      numerous microvilli and pseudopodia with round terminal expansion in contrast to
      the ruffle protrusions and leaf-like pseudopodia of control cells. All the
      results suggested that R II could reverse some malignant phenotypes of MFC cells.

PMID- 7720140
TI  - [The presence and distribution of insulin in rat brain and its relation to
      feeding].
AB  - Using the immunohistochemical method, insulin was proved to exist in cells of
      hypothalamus, thalamus, cerebral cortex, hippocampus, ependyma of third ventricle
      and choroid of rat, including some of the neuronal nuclei, and was further
      confirmed by immunoelectromicroscopy. The insulin concentrations in rat brain
      differed in various regions. Simultaneous determinations of insulin
      concentrations in brain, CSF and blood showed that the brain insulin could not
      originate from blood through CSF. The participation of brain insulin in
      regulating of body energy balance at hypothalamus was illustrated and discussed.

PMID- 7720141
TI  - [The experimental study of immunosuppressive effect of tripchlorolide on the
      cardiac allograft rats].
AB  - In order to confirm the anti-rejection effect of Tripchlorolide (T4), we compared
      the mean survival time of cardiac allograft, scores of pathological damage of the
      heart, the generation of IL-2 from splenocytes stimulated by ConA, and the serum
      level of sIL-2R in the heart transplant model (Lou-->F344) that received either
      cyclosporine or T4. The present study has shown that T4 could prolong the MST of
      cardiac allograft and significantly decrease the degrees of pathological damage
      of the transplant heart. The results indicated that T4 might be used as new anti
      rejection drug in organ transplantation.

PMID- 7720142
TI  - [The effect of nutrition support and recombinant growth hormone on body
      composition and muscle function in postoperative patients].
AB  - To determine the effects of nutritional support and recombinant human growth
      hormone (GH) on body composition and muscle function, we performed a randomized
      double-blind trial in 18 patients after elective gastrectomy or colectomy. Same
      amount of calories and amino acids were administered. Daily injection of GH or
      placebo was given during the first postoperative week. The GH dose was 0.2
      IU/kg/d. The study of body composition demonstrated that control subjects lost
      lean body mass and fat 2.8 +/- 1.46kg and 0.49 +/- 1.3kg, respectively. In
      contrast, study group subjects lost the fat 0.95 +/- 0.46kg. Hand grip strength
      fell with time in the control group (P < 0.05). In contrast, grip strength of GH
      treated subjects was significantly different from controls (P < 0.01). The study
      results demonstrated that nutritional support and growth hormone can maintain
      lean body mass and muscle function in postoperative patients.

PMID- 7720143
TI  - [Comparative study of ultrasonography and pathology of endometrial carcinoma].
AB  - Preoperative sonography was performed in 83 patients with a histologic diagnosis
      of endometrial cancer. The diagnostic accuracy was 84.3%. Five types of
      sonographic pattern were described. The sonographic accuracy in distinguishing
      deep or beyond the uterus invasion from superficial invasion was 92.8%, the
      specificity was 88.2%, and sensitivity was 100%. Tumor stage was correctly
      predicted by sonography in 95.2% of the cases.

PMID- 7720144
TI  - [The clinical characters and treatment of lung cancer in youth].
AB  - From January 1970 to December 1990, 67 patients with lung cancer aged younger
      than 40 years, were treated in the PUMC Hospital. There were 43.3% with SCLC and
      37.3% with adenocarcinoma. Twenty-eight patients underwent resection of the lung.
      Thirty-five cases received chemotherapy or radiotherapy only. The clinical and
      pathological characteristics of lung cancer in youth, and the influence of
      surgical and non=surgical treatments to the patients with lung cancer are
      discussed. The authors consider that the bronchoscopic and sputum smear
      examinations are very helpful for diagnosing lung cancer in the early stage.
      Postoperative adjuvant chemo- and radio-therapy is suggested because of the high
      incidence of SCLC and adenocarcinoma in the young patients with lung cancer.

PMID- 7720145
TI  - [Effect of GG on the occurrence of tongue retropulsion--an experimental
      observation of electromyography].
AB  - To evaluate the effect of GG activity on tongue backwardness during sleep, we
      conducted experiments on 16 rabbits. The electric activities of the muscles
      involved in tongue motion were recorded in different phases (wakefulness,
      presnoring and snoring) with unipolar electrodes inserted into the muscles under
      direct vision. The observations demonstrated that GG played a more active role in
      the occurrence of tongue backwardness during sleep.

PMID- 7720146
TI  - [The frozen bovine RPE cells release a resolvable material which can promote the
      proliferation of RPE cells].
AB  - 3H-thymidine incorporation (as a proliferation maker) confirms that the frozen
      bovine RPE cells release a resolvable material which can promote the
      proliferation of RPE cells, and the molecular weight of the material is more than
      10,000 Daltons. This result provided some new explanations about the effect and
      complications of ophthalmic cryotherapy related to RPE.

PMID- 7720147
TI  - [Studies on triterpenoids of total glucosides of tripterygium wilfordii].
AB  - Three more triterpenoids were isolated from total glucosides of tripterygium
      wilfordii (T1). T16 and T17 were identified as salaspermic acid and as wilforlide
      B. T18 was a new compound. The structure of T18 was determined, as 3-oxo-22 alpha
      hydroxy-delta 12-oleanen-29-oic acid by detail spectroscopic and chemical
      analysis, and named triptotriterpenonic acid A.

PMID- 7720148
TI  - [Comparison of the sensitivity of retinoic acid sensitive and resistant HL-60
      cell lines to several anti-leukemia drugs].
AB  - By using MTT and trypan blue exclusion assay, the sensitivity of retinoic acid
      sensitive HL-60 and resistant HL-60/RA cell to six anti-leukemia drugs such as
      RA, Ara-c, harringtonine was compared. It was found that all five drugs except RA
      exhibited an approximately equivalent IC50 to HL-60 and HL-60/RA cells. The
      results suggest that tumor cells may not develop resistance to differentiation
      inducer and cytotoxic anti-tumor agent parallel. It also suggests that it is
      reasonable to use a combination of differentiation and cytotoxic anti-leukemia
      agents concomitantly or sequentially.

PMID- 7720149
TI  - [Cyclic changes of serum reproductive hormone levels on patients with
      endometriosis and infertility].
AB  - Fourteen cases of endometriosis (Em) with infertility were studied by laparoscopy
      in our hospital from Dec. 1988 to Oct. 1989. 2 cases were minimal, 6 cases were
      moderate and 6 cases were severe. The salpingo examinations of 13 cases were
      normal by laparoscopy. There were no stigma on ovaries in 7 cases (LUFS). Levels
      of hormone (E2,P,LH,FSH) were compared in Em with normal women. The level of E2
      during the follicle phase in Em was lower (86.4 +/- 6.9 pg/ml) than in normal
      women (119.9 +/- 7.7 pg/ml, P < 0.01). The LUFS group was compared with the no
      LUFS group in Em. During the mid-late follicle phase and ovulatory phase, the E2
      values in the LUFS group was significantly lower than in the non-LUFS group (P <
      0.05), while the FSH value in LUFS group was significantly higher than in non
      LUFS group (P < 0.05).

PMID- 7720150
TI  - Quantifying the effect of enflurane on atracurium infusion requirements.
AB  - The present study was designed to evaluate the interaction between atracurium and
      enflurane in 40 adult surgical patients using closed-loop feedback control of
      infusions of atracurium. Anaesthesia was induced with thiopentone and fentanyl
      and intubation was facilitated with atracurium 0.5 mg.kg-1 lean body mass. During
      the first 90 min, anaesthesia was maintained with nitrous oxide in oxygen (2:1)
      and fentanyl. For the following 90 min the patients were randomly assigned to
      receive enflurane at different end-tidal concentrations: Group I, control,
      fentanyl-nitrous oxide anaesthesia; Group II, enflurane 0.3%-nitrous oxide; Group
      III, enflurane 0.6%-nitrous oxide; Group IV, enflurane 0.9%-nitrous oxide. The
      possible interaction of atracurium with enflurane was quantified by determining
      the asymptotic steady-state rate of infusion (ISS) of atracurium necessary to
      produce a constant 90% neuromuscular block. This was accomplished by applying
      nonlinear curve fitting to data on the cumulative dose requirements. Every
      patient served as his/her own control and the changes in the infusion rates were
      determined individually. Patient characteristics and controller performance,
      i.e., the ability of the controller to maintain the neuromuscular blockade
      constant at the setpoint, did not differ among groups. In Group II ISS decreased
      from 0.33 +/- 0.12 to 0.26 +/- 0.08 mg.kg-1.hr-1 (P < 0.01), in Group III from
      0.32 +/- to 0.12 to 0.24 +/- 0.08 mg.kg-1.hr-1 (P < 0.001) and in Group IV from
      0.29 +/- 0.09 to 0.21 +/- 0.09 mg.kg-1.hr-1 (P < 0.001). In the control group
      atracurium requirements remained unchanged throughout the study.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7720151
TI  - Preemptive opioid analgesia does not influence pain after abdominal hysterectomy.
AB  - Opioid administration before surgical stimulus may reduce or prevent subsequent
      pain. We studied the effect of timing of opioid administration on the pain
      related behaviour after abdominal hysterectomy. Eighty-five patients scheduled
      for abdominal hysterectomy were blindly randomized to receive fentanyl 10
      micrograms.kg-1 before induction of anaesthesia (FA), after peritoneal incision
      (FB) or after removal of the uterus (FC), or sufentanil 1 micrograms.kg-1 before
      induction of anaesthesia (SA) or after peritoneal incision (SB) respectively. All
      patients received a standard postoperative analgesic regimen. The time from skin
      closure to the first analgesic request was recorded. Pain was assessed using the
      VAS and a verbal rating score (VSR 1 = no pain to 6 = intolerable pain) every 30
      min until patients asked for the first analgesic, and 24 hr postoperatively. The
      times from skin closure to the first analgesic request did not differ among the
      five groups. The VAS scores using the two-way ANOVA with repeated measurements
      differed among the five groups (F = 4.046, df = 4, 213, P < 0.005). The VAS
      scores with one-way ANOVA differed among the five groups 30 min postoperatively
      (F = 4.542, df = 4, 58, P < 0.003), being higher in the FA (6.5 +/- 1.8) and SA
      (5.9 +/- 2.1) groups than in the FC (3.2 +/- 2.5) group, and at 120 min
      postoperatively (F = 3.217, df = 4, 18, P < 0.05), being higher in the FA than in
      the FB group (6.1 +/- 1.5 and 2.6 +/- 1.9 respectively).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7720152
TI  - Midazolam coinduction does not delay discharge after very brief propofol
      anaesthesia.
AB  - Previous reports have demonstrated synergism of midazolam and propofol for
      induction of anaesthesia in humans. We tested the hypothesis that in the presence
      of alfentanil, the combination of midazolam with propofol for a very brief
      operative procedure would not affect the recovery phase. During pre-oxygenation,
      64 outpatients scheduled for dilatation and curettage received placebo, or low
      dose midazolam (0.03 mg.kg-1), or high-dose midazolam (0.06 mg.kg-1) iv, in a
      randomized double-blind manner. They then received alfentanil 10 micrograms.kg-1
      iv, followed by titrated doses of propofol iv for induction and maintenance of
      anaesthesia. Ventilation with 70% N2O in O2 by mask was controlled to achieve a
      PETCO2 30-40 mmHg. Outcome measures were: propofol dose (induction and
      maintenance), time until eye-opening to command, and time to discharge-readiness.
      Propofol induction dose was decreased by increasing doses of midazolam (P =
      0.00005). Midazolam delayed time to eye-opening (P = 0.02) but not time to
      discharge-readiness. This study had an 80% power to detect a 39 min difference in
      time to discharge-readiness. We conclude that midazolam propofol co-induction in
      the presence of alfentanil delays eye-opening, but does not delay discharge after
      anaesthesia.

PMID- 7720153
TI  - Enhancement of pressor response to intravenous phenylephrine following oral
      clonidine medication in awake and anaesthetized patients.
AB  - Clonidine, an alpha 2-adrenergic agonist, augments the pressor response to
      intravenous ephedrine. If this effect is partly due to clonidine-induced
      potentiation of alpha 1-adrenoceptor-mediated vasoconstriction, it is also
      assumed that clonidine would enhance the pressor effect of phenylephrine as an
      alpha 1-adrenergic agonist. The authors studied haemodynamic responses to
      intravenous phenylephrine in 80 patients who received either preanaesthetic
      medication with clonidine approximately 5 micrograms.kg-1 po (clonidine group, n
      = 40), or no medication (control group, n = 40). Each group was further divided
      into either awake subjects (n = 20) or subjects anaesthetized with enflurane and
      nitrous oxide in oxygen (n = 20). Haemodynamic measurements were made at one
      minute intervals for ten minutes after phenylephrine 2 micrograms.kg-1 iv was
      injected as a bolus. The magnitudes of maximal mean blood pressure increases in
      the clonidine group (26 +/- 7% (mean +/- SD) for awake and 32 +/- 15% for
      anaesthetized subjects) were greater (P < 0.05) than in the control group (13 +/-
      7% for awake and 18 +/- 7% for anaesthetized subjects). However, there was no
      difference in the pressor effect of phenylephrine between awake and anaesthetized
      patients in both groups. Oral clonidine preanaesthetic medication, 5
      micrograms.kg-1, augments the pressor responses to phenylephrine 2 micrograms.kg
      1 iv in awake and anaesthetized patients. These results suggest that the
      enhancement of the pressor responses to phenylephrine following oral clonidine
      may be due to clonidine-induced potentiation of alpha 1-adrenoceptor-mediated
      vasoconstriction. This implies that restoration of blood pressure can be achieved
      effectively by phenylephrine in hypotensive patients with clonidine
      premedication.

PMID- 7720154
TI  - Haemodynamic changes during induced hypotension--comparison of trimethaphan with
      prostaglandin E1 assessed using transoesophageal echocardiography.
AB  - Haemodynamic changes during induced hypotension depend upon the hypotensive agent
      used. We investigated if, using transoesophageal echocardiography (TEE), we could
      identify the haemodynamic differences between trimethaphan and prostaglandin E1.
      Twenty-nine patients undergoing total hip replacement were selected for study.
      Hypotension was induced to a mean arterial pressure of 8.0-9.3 kPa with either
      trimethaphan (5-20 micrograms.kg-1.min-1) or prostaglandin E1 (0.5-2.0
      micrograms.kg-1.min-1). The left atrial dimension, cardiac output, fractional
      shortening, pulmonary venous flow and mitral valve flow were evaluated using TEE.
      During induced hypotension, left atrial dimension decreased in both trimethaphan
      and prostaglandin E1 groups (P < 0.05). In the trimethaphan-treated patients
      systolic velocity in pulmonary venous flow decreased from 41.9 +/- 4.8 cm.sec-1
      before induced hypotension to 27.8 +/- 4.2 cm.sec-1 by 30 min after stable
      hypotension had been established (P < 0.01). The late/early ratio of peak
      velocity in mitral blood flow decreased in prostaglandin E1 treated patients.
      Cardiac output increased from 4.2 +/- 0.5 L.min-1 to 5.3 +/- 0.4 L.min-1 during
      30 min hypotension with prostaglandin E1 administration (P < 0.05), but cardiac
      output decreased from 5.0 +/- 0.5 to 3.5 +/- 0.4 L.min-1 with trimethaphan (P <
      0.01). The differences in haemodynamic variables could be attributed to the
      venule dilatation effect of trimethaphan. We conclude that it was possible to
      detect the haemodynamic differences between trimethephan and prostaglandin E1
      using TEE.

PMID- 7720155
TI  - The laryngeal mask airway in obstetrical anaesthesia.
AB  - The laryngeal mask airway (LMA) has been used extensively to provide a safe
      airway in spontaneously breathing patients who are not at risk from aspiration of
      gastric contents. The role of the LMA in the event of a failed intubation in an
      obstetrical patient, and its place in a failed intubation drill remains unclear.
      Two hundred and fifty consultant obstetric anaesthetists in the United Kingdom
      were asked to complete an anonymous questionnaire regarding their views about
      using the laryngeal mask airway (LMA) in obstetrical anaesthesia. The LMA was
      available in 91.4% of obstetric units. Seventy-two per cent of anaesthetists were
      in favour of using the LMA to maintain oxygenation when tracheal intubation had
      failed and ventilation using a face mask was inadequate. Twenty-four respondents
      had had personal experience with the LMA in obstetrical anaesthesia, eight of
      whom stated that the LMA had proved to be a lifesaver. We believe that the LMA
      has a role in obstetrical anaesthesia when tracheal intubation has failed and
      ventilation using a face mask proves to be impossible, and it should be inserted
      before attempting cricothyroidectomy.

PMID- 7720156
TI  - Resuscitation and DNR: ethical aspects for anaesthetists.
AB  - Autonomy is a central ethical principle of medical practice. The physician's
      autonomy is usually expressed in concert with the other, overriding, ethic of
      medical care: beneficence. The autonomy of patients, however, has had a growing
      influence on medical decision-making and can complicate the process. One area
      where this is especially true is the manner in which cardiopulmonary
      resuscitation is disallowed: the do-not-resuscitate (DNR) order. Cardiopulmonary
      resuscitation initially was a therapy automatically instituted in emergencies
      because it was life-saving. Data began to show, however, that this drastic
      measure was not always effective. Therefore, its use began to be limited through
      DNR orders, and policies about DNR orders have been developed to ensure it, in
      turn, is instituted properly. Besides being used when CPR is futile, the DNR
      order also serves as a formal means of accounting for a patient's autonomy. Data
      show, however, that patients are not routinely consulted on this issue even
      though they want to discuss it. In these cases, quality of life, a patient's
      subjective evaluation, serves as the basis of a DNR order and makes mandatory
      communication between physician and patient. Such communication, however, can be
      obstructed by social values about life and death and the urgent nature of medical
      care in these situations. To show how such communication ought to be incorporated
      into medical decision-making, one of the most difficult situations is examined
      hypothetically: the patient who has a DNR order but who consents to undergo
      anaesthesia and surgery. In these cases, frequent communication between physician
      and patient about each therapy and its effect most often will resolve dilemmas.

PMID- 7720157
TI  - Monitoring complication due to a pulsatile femoral vein from tricuspid
      regurgitation.
AB  - This clinical report illustrates a monitoring complication due to a pulsatile
      femoral vein from tricuspid regurgitation. In this case, the femoral vein of a
      patient was inadvertently cannulated and exhibited a pulsatile tracing which was
      mistaken for an arterial pressure tracing. This led to the initial inappropriate
      use of vasopressors which actually augmented the pulsatility and delayed
      detection of the error. Although this may be a rare occurrence, the clinician
      should be aware of its possibility when using invasive monitoring in a patient
      with tricuspid regurgitation.

PMID- 7720158
TI  - Does experience influence the forces exerted on maxillary incisors during
      laryngoscopy? A manikin study using the Macintosh laryngoscope.
AB  - The influence of the level of experience of the laryngoscopist on the duration of
      laryngoscopy, the forces exerted on the tongue and on the maxillary incisors
      during laryngoscopy, were investigated. Five groups (anaesthetists, residents in
      anaesthesia, nurse anaesthetists, surgeons and medical students), each consisting
      of 15 individuals, participated in the study. An intubation manikin was used with
      a laryngoscope modified so that the forces applied during laryngoscopy could be
      measured. The mean duration of laryngoscopy in these groups was 23.4 sec, 17.6
      sec, 27.1 sec, 26.8 sec and 42.7 sec, respectively. The maximally applied forces
      on the tongue were 71.7 N, 60.5 N, 65.9 N, 74.2 N and 69.7 N, respectively. The
      maximally applied forces on the maxillary incisors were 49.9 N, 36.3 N, 41.1 N,
      58.3 N and 53.9 N, respectively. These results indicate the level of experience
      has a significant influence on the duration of laryngoscopy but seems to have
      little influence on the forces applied to the tongue and the maxillary incisors.

PMID- 7720159
TI  - Actions of propofol on pontine neurons controlling arterial pressure in rats.
AB  - Tonic firing of pontine neurons provides excitatory input to the vasomotor centre
      in the ventrolateral medulla. To increase our understanding of the actions of
      propofol on CNS neurons controlling the cardiovascular system, we evaluated the
      effects of propofol on this tonic firing of pontine neurons. The actions of
      propofol (doses 1-4, respectively: 24 +/- 2, 40 +/- 4, 65 +/- 3 and 104 +/- 3
      mg.kg-1.hr-1) on the pontine neurons were studied using eight atropinized Wistar
      rats. Electrical activity of renal sympathetic nerves, systemic arterial blood
      pressure and heart rate were recorded. Propofol decreased renal nerve activity by
      3 +/- 2%, 23 +/- 3%, 33 +/- 3% and 52 +/- 4% at the four doses. Arterial pressure
      and heart rate decreased similarly in a dose-dependent manner. Sympathetic and
      cardiovascular responses to blocking neurons in the pontine reticular formation
      by microinjection of glycine were depressed by propofol. Renal nerve activity was
      decreased by 44 +/- 5% 41 +/- 4%, 28 +/- 3% and 13 +/- 2% after pontine blockade
      during infusion of doses 1 to 4, respectively. Similarly, arterial pressure was
      decreased by 25 +/- 3, 15 +/- 2, 12 +/- 1 and 5 +/- 2 mmHg. Finally, heart rate
      decreased by 27 +/- 6, 20 +/- 4, 18 +/- 4 and 13 +/- 5 heats per min as the
      propofol dose increased. The tonic firing of pontine neurons was minimally
      depressed by the lower two doses of propofol but higher doses did appear to
      depress their firing, demonstrating dose-dependence of actions of this
      anaesthetic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720160
TI  - Effect of cocaine on the contracture response to 1% halothane in patients
      undergoing diagnostic muscle biopsy for malignant hyperthermia.
AB  - Two case reports have cited the recreational use of cocaine as possible trigger
      of a malignant hyperthermia (MH) crisis. We evaluated whether toxic
      concentrations of cocaine altered the in vitro muscle response to halothane
      during contracture tests for MH. Twenty-two patients were studied. Muscle
      biopsies were obtained and first tested for MH susceptibility with 3% halothane
      and caffeine contracture testing. Ten patients were diagnosed as MH-susceptible
      and 12 as MH non-susceptible, in accordance with the North American Malignant
      Hyperthermia Group protocol. Then, muscle strips were exposed to 1% halothane in
      the presence and absence of 0.1 mmol.L-1 cocaine. Cocaine alone did not affect
      baseline muscle tension in either group. With 1% halothane, MH non-susceptible
      muscle showed no contracture with or without cocaine. In contrast, in the
      presence of 1% halothane, MH-susceptible muscle showed either no change in
      contracture (six patients), an increase (two patients), or a decrease (two
      patients) when exposed to cocaine. However, the overall effect of cocaine on
      muscle contracture in the presence of 1% halothane was insignificant in both
      groups. We conclude that cocaine, even at toxic levels, does not have a direct
      effect on skeletal muscle contractility and thus is safe for MH-susceptible
      patients.

PMID- 7720161
TI  - Does the initial distribution volume of glucose reflect plasma volume after
      haemorrhage in dogs?
AB  - To test the hypothesis that the initial distribution volume of glucose (IDVG)
      reflects plasma volume, the relationship between the IDVG and indocyanine green
      (ICG) assessments of plasma volume (Vd-ICG) were evaluated simultaneously both
      before and after induced haemorrhage (30 ml.kg-1) in eight mongrel dogs. The IDVG
      and the Vd-ICG were calculated with a one-compartment model from repeated
      measurements of plasma glucose three to seven minutes, and of plasma ICG three to
      nine minutes after simultaneous infusions of both glucose 100 mg.kg-1 and ICG 0.5
      mg.kg-1. The IDVG calculated with a one-compartment model (IDVG-OCM) was also
      compared with a two-compartment model within 15 min (IDVG-TCM) on nine occasions
      among a total of 12 determinations. Using Bland and Altman analysis to compare
      the two analytical models, the IDVG-OCM tends to overestimate the IDVG-TCM by an
      average of 0.04 L. Although the IDVG-OCM was two to three times larger than the
      Vd-ICG at each corresponding point, a correlation was obtained between the IDVG
      OCM and the Vd-ICG before and after induced haemorrhage (r = 0.85, n = 16, P <
      0.001). We conclude that the IDVG reflects plasma volume in normal and
      hypovolaemic dogs, although the IDVG cannot be used directly to estimate plasma
      volume.

PMID- 7720162
TI  - Anaesthetic management of a patient with a descending thoracic aortic aneurysm
      and severe bilateral bullous pulmonary parenchymal disease.
AB  - The anaesthetic management of the surgical repair of a descending aortic aneurysm
      in a patient with large, bilateral, pulmonary bullae is described. Anaesthesia
      for descending aortic surgery normally involves unilateral, positive-pressure
      ventilation, an option which poses some risk of barotrauma in the presence of
      bilateral bullae. Patients with bullous disease commonly have severe lung disease
      and thorough preoperative assessment and preparation are necessary.
      Intraoperatively, bilateral rupture of the bullae could be catastrophic and
      preparations should be made for this possibility. In order to diminish this risk,
      a surgical technique including preemptive collapse of the bulla by
      minithoracotomy and tube drainage, with use of a bronchial blocker to the
      affected part of the lung may be used. If rupture occurs, then high frequency jet
      ventilation may be effective. Use of a double lumen endobronchial tube may be
      advantageous for patients with either unilateral and bilateral bullae.
      Anaesthesia for patients with bullae should avoid positive-pressure ventilation
      and nitrous oxide in order to limit the risk of barotrauma from a ball valve
      mechanism. In this case, the risk of barotrauma was reduced by performing an
      inhalational induction of anaesthesia and limiting peak inflation pressures
      during thoracotomy. It was elected to use positive-pressure ventilation through a
      double lumen endobronchial tube following chest incision. A high frequency jet
      ventilator was available but not employed. Anaesthetic management was complicated
      by the presence of pleural adhesions, surgical approach directly through a bulla,
      and the requirement for one lung ventilation.

PMID- 7720163
TI  - Anaesthesia by intravenous emulsified isoflurane in mice.
AB  - An emulsion of isoflurane in Intralipid for intravenous (iv) injection was
      formulated and its anaesthetic properties determined in mice. The major advantage
      of iv delivery of volatile agents is to accelerate the induction of anaesthesia
      by circumventing the anesthetic circuitry and the lung's functional residual
      capacity. Isoflurane was added to Intralipid in varying concentrations. The ED50
      (n = 34) and LD50 (n = 20) were determined by a single iv bolus injection.
      Anaesthesia was also induced and maintained for 30 min (n = 5) by continuous
      infusion and the time to emergence was measured. The ED50 and LD50 were 0.7 +/-
      0.2 microliter and 2.4 +/- 0.2 microliter of isoflurane equivalent respectively.
      An average infusion rate of 1.6 +/- 0.4 microliters.min-1 of isoflurane
      equivalent was required for maintenance following which the average emergence
      time was 193 +/- 35 secs. The only negative effect was local skin ulceration with
      an inadvertent interstitial injection. We conclude that iv induction and
      maintenance with emulsified isoflurane in Intralipid can be carried out with
      safety and reproducibility in the mouse. Further larger animal studies are
      warranted assessing the haemodynamic, toxicological, physiochemical and
      pharmacokinetic characteristics of these and other similar preparations.

PMID- 7720164
TI  - Anaesthesia and past use of LSD.

PMID- 7720165
TI  - A new solution to fibreoptic intubation in the presence of blood and secretions.

PMID- 7720166
TI  - Myasthenia gravis and regional anaesthesia.

PMID- 7720167
TI  - How much relaxation?

PMID- 7720168
TI  - Surgeon-controlled mivacurium administration during elective caesarean section.
AB  - We have compared the dose requirements and recovery characteristics of a
      continuous mivacurium infusion given by the anaesthetist to maintain 95-100%
      block at the hand muscles with that of a surgeon-controlled, on-demand dosing
      technique based on the direct assessment of abdominal muscle tone during elective
      Caesarean section. Twenty-four full term pregnant patients were included. A rapid
      sequence induction using thiopentone 3-5 mg.kg-1 and succinylcholine 1 mg.kg-1
      was used. Anaesthesia was maintained with fentanyl, N2O and isoflurane 0.5%. The
      mechanomyographic response of the adductor pollicis muscle to supramaximal train
      of-four (TOF) ulnar nerve stimulation was recorded. Muscle relaxation was
      achieved initially with mivacurium 0.1 mg.kg-1 followed either by a continuous
      infusion of mivacurium to maintain 95-100% block at the adductor pollicis muscle
      (n = 12) or by surgeon-controlled relaxation (SCR) technique using a syringe pump
      for patient-controlled analgesia to administer on-demand doses of mivacurium 0.05
      mg.kg-1 (n = 12). The lockout interval was three minutes and the maximum hourly
      dose of mivacurium allowed was 0.6 mg.kg-1. The total doses of mivacurium (mean
      +/- SD) were 23.2 +/- 10.4 and 12.4 +/- 3.5 mg in the infusion and SCR groups, P
      < 0.01. On-demand, surgeon-controlled doses of mivacurium were injected at a mean
      of T1 42.3 +/- 36%. At the end of surgery, T1 and TOF ratio were respectively
      16.7 +/- 13%, 5 +/- 10% and 48 +/- 37%, 30 +/- 24% in the infusion and SCR
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720169
TI  - Delivery and cytotoxicity of RS-1541 in St-4 human gastric cancer cells in vitro
      by the low-density-lipoprotein pathway.
AB  - RS-1541 is a 13-O-palmitoyl derivative of rhizoxin, an inhibitor of tubulin
      polymerization. RS-1541 has been shown to bind preferentially to plasma
      lipoproteins and to exhibit selective and sustained uptake by tumors in mice. To
      elucidate a mechanism of RS-1541 cytotoxicity, the cellular uptake and the
      cytotoxicity of a complex of RS-1541 with human low-density lipoprotein (RS
      1541/LDL complex) were investigated in cultured St-4 human gastric cancer cells.
      Both the cellular uptake and the cytotoxicity of the RS-1541/LDL complex were
      greater in cells with higher LDL-receptor activities than in control cells.
      Excess amounts of LDL or 1 microM of monensin, a proton ionophore, significantly
      inhibited both the uptake and the cytotoxicity of the complex. Chloroquine, an
      inhibitor of lysosomal enzymes, decreased the intracellular level of rhizoxin
      liberated from RS-1541 and suppressed the cytotoxicity of the RS-1541/LDL
      complex. However, a detergent-aided solution of RS-1541 showed very low cellular
      uptake and cytotoxicity, irrespective of the LDL-receptor activities of these
      cells. These results demonstrate that the RS-1541/LDL complex is incorporated
      into the cells via the LDL receptor and that it manifests its cytotoxic activity
      after forming rhizoxin, the original antitumor agent, in the lysosomes.

PMID- 7720170
TI  - Activity of melphalan in combination with the glutathione transferase inhibitor
      sulfasalazine.
AB  - Glutathione (GSH) transferases (GST), a family of detoxification enzyme proteins,
      are suggested to play an important role in tumor cell resistance to melphalan.
      The GST-activity inhibitor ethacrynic acid has been shown to increase the
      antitumor activity of melphalan in vitro as well as in vivo. In this study we
      determined the activity and toxicity of melphalan in combination with another GST
      activity inhibitor, sulfasalazine, an agent used to treat ulcerative colitis. We
      entered 37 previously treated patients with advanced cancer of different
      histologies on sulfasalazine given at the individually calculated maximum
      tolerated dose (MTD) and melphalan given at doses beginning at 20 mg/m2. The main
      toxicity arising from this combination was nausea and vomiting, whereas increased
      myelosuppression was not observed. A partial response was seen in 2/4 of the
      ovarian cancer patients only. Plasma sulfasalazine levels varied between 2.5 and
      47.1 micrograms/ml. Although reductions in GSH/GST levels were observed in
      peripheral mononuclear cells of certain patients following sulfasalazine
      treatment, there was no correlation between the extent of reduction and the
      plasma sulfasalazine level. A larger patient population must be studied to
      determine the usefulness of this combination.

PMID- 7720171
TI  - Detoxification ability and toxicity of quinones in mouse and human tumor cell
      lines used for anticancer drug screening.
AB  - The in vitro testing of antitumor drugs involves the use of mouse and human tumor
      cells. In particular, there is interest in developing agents active against human
      solid tumors. We examined several biochemical parameters that may contribute to
      the differential sensitivity of the cell lines used in our laboratory to the
      toxic effects of antitumor compounds. The tumor cell lines examined were of mouse
      (colon 38, L1210 leukemia, and C1498 leukemia) and human origin (CEM leukemia,
      CX1 colon, H116 colon, HCT8 colon and H125 lung). Quinone reductase activity was
      markedly different between leukemia and solid-tumor cell lines of either mouse or
      human origin, with increased activity being observed in the solid-tumor cell
      lines relative to the leukemia lines. GSH transferase activity also was generally
      increased in solid-tumor relative to leukemia cell lines. Superoxide dismutase
      activity and thiol levels were similar in leukemia and solid-tumor cell lines,
      except that thiol levels were very low in colon 38. Mouse cell lines from in
      vitro passage had somewhat higher activity of superoxide dismutase and thiol
      levels than did cells maintained in vivo, indicating relatively increased
      antioxidant defenses. The toxicity of 2,3-dimethoxy-1,4-naphthoquinone, a model
      quinone that exerts its toxic effects via production of reactive oxygen species,
      was significantly lower in mouse lines maintained in vitro than in those tested
      in vivo, whereas the toxicity of another quinone, menadione, was just slightly
      lower. Quinone reductase activity, GSH transferase activity, and thiol levels
      were significantly higher in the human lines than in the mouse lines.
      Accordingly, the toxicity of both quinones tended to be lower in the human lines
      than in the mouse lines.

PMID- 7720172
TI  - Antitumor effect of intratumoral administration of fluorouracil/epinephrine
      injectable gel in C3H mice.
AB  - Fluorouracil/epinephrine injectable gel (5-FU/epi gel) was evaluated in vitro for
      its drug-release profile characteristics and in a mouse tumor model for its
      antitumor effectiveness. In vitro chemosensitivity studies with 5-FU in RIF-1
      fibrosarcoma cells showed less than 1 log of cell kill at 1 mM after 2 h of
      exposure. Increasing the exposure time to 24 h resulted in greater cell killing
      (approximately 2.5 log cell kill at 0.5 mM), suggesting that sustained drug
      levels in tumors would result in an increased efficacy outcome in vivo. A 5
      FU/epi injectable gel was designed, providing drug release in vitro of 50% by
      approximately 4 h and of 80% by 24 h. The retention of 5-FU in RIF-1 mouse tumors
      was determined after intratumoral administration of 5-FU/epi gel or various
      combinations of the formulation components. Area-under-the-curve (AUC0-24 h)
      calculations resulted in an AUC value of 146.4% h for the 5-FU/epi gel
      formulation as compared with 45.7% h for 5-FU solution. Tumor growth was
      significantly delayed (P < 0.05) with the 5-FU/epi gel (60 mg/kg) as compared
      with 5-FU solution given intratumorally or systemically. A fluorouracil dose of
      150 mg/kg in the 5-FU/epi gel given weekly for 13 weeks was not lethally toxic,
      whereas the same dose given as drug solution was 100% lethal, suggesting that the
      therapeutic index for 5-FU in the gel formulation may be much greater than that
      for aqueous drug solution delivered intratumorally.

PMID- 7720173
TI  - Pharmacokinetic evaluation of zeniplatin in humans.
AB  - Zeniplatin, a more water-soluble organoplatinum than cisplatin, was evaluated for
      clinical pharmacology in the context of a phase II trial in previously treated
      patients with ovarian carcinoma. A total of 12 patients were given zeniplatin at
      120 mg/m2 by rapid intravenous infusion over 90 min, with both blood and urine
      being sampled. All platinum moieties were analyzed in whole blood, plasma, plasma
      ultrafiltrate, and urine by atomic absorption, and free zeniplatin was analyzed
      in plasma ultrafiltrate by specific high-performance liquid chromatography
      (HPLC). In a comparison of the platinum-time concentration curve, AUC (area under
      the curve) values indicated that approximately 90% of platinum moieties were
      bound to circulating plasma proteins. There was no evidence of drug accumulation
      after repetitive dosing. The terminal half-life (t1/2) of this drug in plasma
      ultrafiltrate (3.7-7.2 h.) as measured by HPLC was slightly longer than that of
      carboplatin, whereas total platinum moieties in plasma displayed a long t1/2 (124
      154 h). Approximately 60% of platinum moieties could be recovered in the urine
      within 24 h. These findings suggest that zeniplatin has a pharmacokinetic profile
      similar to that of carboplatin.

PMID- 7720174
TI  - Extensive and saturable accumulation of paclitaxel by the human platelet.
AB  - Little is known about the cellular distribution of paclitaxel in humans. In the
      present study we examined the distribution of [3H]-paclitaxel in human blood.
      When 1 microM paclitaxel was incubated with fresh blood at 37 degrees C, the
      platelet/plasma concentration ratio was 240 +/- 17 (mean +/- SEM), whereas the
      red blood cell (RBC)/plasma concentration ratio was only 0.59 +/- 0.05. In
      kinetics experiments using platelet-rich plasma, we observed that the platelet
      accumulation of paclitaxel was highly temperature- and concentration-dependent.
      Scatchard analysis of the 37 degrees C uptake data demonstrated a dissociation
      constant (Kapp) of 0.80 +/- 0.10 microM and a maximal binding capacity of 672 +/-
      102 pmol/10(9) platelets. It is proposed that the platelet accumulation of
      paclitaxel reflects binding to microtubules and may serve as a useful model for
      binding to less accessible cellular sites.

PMID- 7720175
TI  - Therapeutic efficacy of the cyclopropylpyrroloindole, carzelesin, against
      xenografts derived from adult and childhood solid tumors.
AB  - The therapeutic efficacy of the sequence-selective, DNA minor-groove-binding
      alkylating agent carzelesin was evaluated against a series of human tumor
      xenografts growing at the s.c. site. The model consisted of seven colon
      adenocarcinomas, and six pediatric rhabdomyosarcomas. In addition, carzelesin was
      evaluated against xenografts selected in situ for resistance to vincristine,
      melphalan, and topotecan. Carzelesin was given as a single i.v. injection, and
      tumor volumes were determined at 7-day intervals. At the highest dose [0.5 mg/kg,
      the dose producing 10% lethality (LD10)]), carzelesin significantly inhibited
      growth in four of six colon tumor lines, causing a high proportion of partial
      regressions in one of seven lines and complete regressions of VRC5 colon tumors.
      At 0.25 mg/kg, significant growth inhibition was determined in only two of seven
      colon tumor lines with infrequent volume regressions. Carzelesin given at the
      highest nonlethal dose level significantly inhibited the growth of each of six
      rhabdomyosarcomas, causing a high frequency of partial or complete regressions in
      four of six tumor lines. There was no apparent cross-resistance to carzelesin in
      two rhabdomyosarcomas selected for vincristine resistance (Rh12/VCR, Rh18/VCR) or
      in Rh28/LPAM xenografts selected for primary resistance to the bifunctional
      alkylating agent melphalan. Interestingly, carzelesin maintained full activity
      against Rh18/TOPO tumors selected in situ for resistance to topotecan, whereas
      the colon tumor VRC5/TOPO, selected in a similar manner, was completely resistant
      to this agent.

PMID- 7720176
TI  - The kinetics of the auto-induction of ifosfamide metabolism during continuous
      infusion.
AB  - It has often been reported that the oxazaphosphorines ifosfamide and
      cyclophosphamide induce their own metabolism. This phenomenon was studied in 21
      paediatric patients over 35 courses of therapy. All patients received 9 gm-2 of
      ifosfamide as a continuous infusion over 72 h. Plasma concentrations of parent
      drug and of the major metabolite in plasma, 3-dechloroethylifosfamide (3DC) were
      determined, using a quantitative thin-layer chromatography (TLC) technique. A one
      compartment model was fitted simultaneously to both ifosfamide and 3DC data. The
      model included a time-dependent clearance term, increasing asymptotically from an
      initial value to a final induced clearance and characterised by a first-order
      rate constant. A time lag, before induction of clearance began, was determined
      empirically. Metabolite kinetics were characterised by an elimination rate
      constant for the metabolite and a composite parameter comprising a formation
      clearance, proportional to the time-dependent clearance of parent drug, divided
      by the volume of distribution of the metabolite. Thus, the parameters to estimate
      were the volume of distribution of parent drug (V), initial clearance (Cli),
      final clearance (Cls), the rate constant for changing clearance (Kc), the
      elimination rate constant for the metabolite (Km) and Vm/fm, the metabolite
      volume of distribution divided by the fractional clearance to 3DC. The model of
      drug and metabolite kinetics produced a good fit to the data in 22 of 31 courses.
      In a further 4 courses an auto-inductive model for parent drug alone could be
      used. In the remaining courses, auto-induction could be demonstrated, but there
      were insufficient data to fit the model. For some patients this was due to a long
      time lag (up to 54 h) relative to the infusion time. The time lag varied from 6
      to 54 (median, 12)h and values for the other parameters were Cli, 3.27 +/- 2.52
      lh-1 m-2, Cls, 7.50 +/- 3.03 lh-1 m-2, V, 22.0 +/- 11.0 1 m-2, Kc, 0.086 +/-
      0.074 h-1; Km, 0.159 +/- 0.077 h-1 and Vm/fm, 104 +/- 82 1m-2. The values of Kc
      correspond to a half-life of change in clearance ranging from 2 to 157 h,
      although for the majority of the patients the half-life was less than 7 h and a
      new steady-state level was achieved during the 72 h infusion period. This model
      provides insight into the time course of enzyme induction during ifosfamide
      administration, which may continue for up to 10 days in some protocols.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7720177
TI  - A preclinical model for sequential high-dose chemotherapy.
AB  - Dose-intensive chemotherapy regimens have entered clinical trial based on the
      notion that log-linear tumor-cell killing, especially with antitumor alkylating
      agents, is maintained at higher drug doses. Several clinical trials employing two
      intensifications are underway. Using the tumor-cell survival assay, animals
      bearing the FSaII fibrosarcoma were treated with single doses of various
      chemotherapeutic agents once or twice with a 3- or 7-day interval between the
      drugs. Isobologram methodology was used to determine if the sequential treatment
      regimens resulted in subadditive, additive or greater-than-additive tumor-cell
      killing. When melphalan was followed 3 or 7 days later by a second dose of
      melphalan there was evidence of resistance to the second dose of melphalan as
      indicated by subadditive tumor-cell killing. Melphalan followed 3 days later by
      cyclophosphamide (300 mg/kg) produced greater-than-additive tumor-cell killing,
      however, when the interval was 7 days the resulting tumor-cell killing was
      subadditive. Melphalan followed 3 or 7 days later by thiotepa or carboplatin
      produced subadditive-to-additive tumor-cell killing. Adriamycin followed 3 days
      later by melphalan, cyclophosphamide, thiotepa, or carboplatin resulted in
      subadditive-to-additive tumor-cell killing by the combinations. These results
      indicate that sequential drug-intensive treatments may not optimize tumor-cell
      killing in vivo.

PMID- 7720178
TI  - A phase I trial of high-dose oral tamoxifen and CHOPE.
AB  - Drug resistance is a common phenomenon in clinical oncology. In vitro, tamoxifen
      has been shown to be an effective inhibitor of P-glycoprotein and a modulator of
      the multidrug resistance phenotype. We have previously shown that vinblastine can
      be given safely in combination with tamoxifen at doses that may modulate P
      glycoprotein activity. In this phase I trial, tamoxifen (150 mg/m2 twice a day)
      was given with CHOPE
      (cyclophosphamide/doxorubicin/vincristine/prednisone/etoposide) in order to
      assess the toxicities of the combination. Resistance to three of these cytotoxic
      agents (doxorubicin, vincristine, and etoposide) may be mediated by P
      glycoprotein. A total of 13 patients were evaluable on this trial, which showed
      that the maximum tolerated doses of cyclophosphamide and etoposide were 750 and
      80 mg/m2, respectively. The dose-limiting toxicity was myelosuppression with 50%
      of the patients (3/6) treated at this dose level developing febrile neutropenia
      and 85% (6/7) developing grade 4 neutropenia. Tamoxifen at a dose of 150 mg/m2
      twice a day can be given safely with the lymphoma regimen CHOPE at standard
      doses, but this combination may result in increased myelosuppression.

PMID- 7720179
TI  - Growth and biochemical effects of unsymmetrically substituted polyamine analogues
      in human lung tumor cells 1.
AB  - Three unsymmetrically substituted polyamine analogues demonstrate significant and
      selective antitumor effects. Each of the analogues N1-ethyl-N11-propargyl-4,8
      diazaundecane (PENSpm), N1-ethyl-N11-(cyclobutyl)methyl-4,8-diazaundecane
      (CBENSpm), and N1-ethyl-N11-(cyclopropyl)methyl-4,8-diazaundecane (CPENSpm) is
      cytotoxic to a representative non-small-cell lung carcinoma line, NCI H157, while
      being only growth-inhibitory to a representative small-cell-lung carcinoma line,
      NCI H82. Cytotoxicity is accompanied by a significant increase in expression of
      the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) at
      the levels of activity and steady-state mRNA. These new analogues are significant
      both for their cell-type-specific activity and as synthetic prototypes for the
      addition of SSAT-activated functional groups.

PMID- 7720180
TI  - Long-term platinum excretion in patients treated with cisplatin.
AB  - The purpose of this study was to determine long-term renal platinum excretion
      after chemotherapy with cisplatin. We examined urinary platinum concentrations in
      23 men at 150-3022 days after anticancer treatment for testicular neoplasm. Spot
      urine samples were analyzed by voltammetry. This new, subtle method with a
      detection limit of 2 pg platinum allows determination of even the natural
      background level. Urinary platinum concentrations in our patients ranged between
      0.74 and 77.24 micrograms/g creatinine, depending on the total delivered dose and
      follow-up period. Regression analysis of the data showed two phases of long-term
      renal platinum excretion, one occurring at between 150 and 900 days of follow-up
      and the other with an onset at 900 days after cisplatin administration (r1(2) =
      0.82, r2(2) = 0.88). Two biological half-lives of 160 and 720 days were
      calculated. Our results show that urinary platinum concentrations determined at 8
      years after cisplatin therapy are 40 times higher than the background level (up
      to 0.02 micrograms/g creatinine). Our findings on the long-term pharmacokinetics
      of this anticancer agent may facilitate further studies on sites of platinum
      storage in the human body as well as clinical studies on the late adverse effects
      of cisplatin.

PMID- 7720181
TI  - Pharmacokinetics of irinotecan and its metabolites in human blood, bile, and
      urine.
AB  - Two patients were treated with CPT-11 for colorectal cancer and had a
      percutaneous biliary catheter for extrahepatic biliary obstruction. The first
      patient was treated with CPT-11 according to the 100-mg/m2 weekly therapeutic
      schedule, and the second patient was treated every 3 weeks, with a dose of 350
      mg/m2 being given at the first course, after which it was decreased to 300 mg/m2
      for the following courses. In plasma, the active identified metabolite of CPT-11,
      SN-38, occurred mainly in the form of a glucuronide conjugate. CPT-11 was mainly
      excreted in bile and urine as CPT-11. The cumulative biliary and urinary
      excretion of CPT-11 and its metabolites (SN-38 and SN-38 glucuronide conjugate)
      over a period of up to 48 h ranged from 25% (100 mg/m2 weekly) to 50% (300 mg/m2
      every 3 weeks). This means that CPT-11 can be excreted under other, not yet
      identified metabolite forms.

PMID- 7720182
TI  - Distribution of cisplatin in perilymph and cerebrospinal fluid after intravenous
      administration in the guinea pig.
AB  - The concentration of free cisplatin was followed in plasma, scala tympani
      perilymph and cerebrospinal fluid (CSF) after an intravenous injection (12.5
      mg/kg) in guinea pigs. Liquid chromatography with postcolumn derivatization was
      used for quantitative determination of the drug. The distribution of cisplatin to
      CSF was fast; at 10 min after drug administration the concentration was 7
      micrograms/ml and the CSF:plasma ratio was 0.37. Cisplatin seems to distribute
      more slowly to the perilymphatic compartment. The highest concentration measured
      was 4 micrograms/ml at 20 min after the injection, and the perilymph:plasma ratio
      was 0.40 at that time. The concentration-time curves generated for cisplatin in
      perilymph and CSF were similar. No accumulation in the perilymphatic compartment
      or CSF was observed.

PMID- 7720183
TI  - Increased cation transport in mdr1-gene-expressing K562 cells.
AB  - Cation-transport properties were compared in a human leukemic cell line (K562)
      and its vincristine-selected, mdr1-gene-expressing sublines (K562/Vcr30 and
      K562/Vcr150) by the capacity of the cells to accumulate the potassium analogue
      thallium (201Tl). Determination of the time course of thallium accumulation in
      the absence and presence of ouabain, an inhibitor of sodium-potassium adenosine
      triphosphatase (ATPase), showed that the initial (at 20 min) rate of ouabain
      resistant uptake was about 70% higher in the K562/Vcr30 cells than in the
      parental line. The maximal rate (Vmax) of ouabain-resistant uptake was 78 mmol/h
      for K562 cells and 115 mmol/h for K562/Vcr30 cells, and the Michaelis constant
      (Km) was 0.37 and 0.18 mmol, respectively. Bumetanide (50 microM), a specific
      inhibitor of ouabain-resistant Na-K-Cl cotransport, inhibited the elevated 201Tl
      uptake in K562/Vcr150 cells but had no effect on cellular vincristine
      accumulation. Incubation with different multidrug resistance (MDR)-reversing
      agents (verapamil as well as cyclosporin A and its analogue PSC833) had no
      significant effect on 201Tl uptake. Membrane depolarization by an elevation of
      the potassium concentration in the incubation medium did not affect vincristine
      accumulation in any cell line, which indicated that the changed drug-transport
      properties in mdr1-gene-expressing cells were not due to membrane
      hyperpolarization. It was concluded that P-glycoprotein-positive cells have a
      more efficient ouabain-resistant cation-transport mechanism than to cells without
      P-glycoprotein. A functional relationship between this phenomenon and MDR was not
      identified.

PMID- 7720184
TI  - Cell cycle effects of hypertonic stress on various human cells in culture.
AB  - Long-term exposure to hypertonic (HT) culture media has been found to perturb the
      cell cycle and change gene expression in various animal cell types. A lower
      growth rate, with exit of cells from the cycling compartment has been observed
      previously in human transformed EUE cells. The aim of this study was to
      investigate if the kinetic changes after long-term HT stress, were typical of
      transformed cells or could be also found in primary cultures of normal cells.
      Human transformed cells from normal and neoplastic tissues, and normal human
      cells of epithelial and connective origin have been studied. After the
      incorporation of bromodeoxyuridine (BrdUrd), the frequency of S-phase cells was
      estimated by dual-parameter flow cytometry of DNA content versus BrdUrd
      immunolabelling; the total growth fraction was also estimated, after
      immunolabelling with an anti-PCNA antibody. We also investigated, by
      polyacrylamide gel electrophoresis, changes in the amount of a 35 kDa protein
      band, which increased in EUE cells grown in an HT medium, and which may be
      directly involved in cell resistance to hypertonicity. Lower BrdUrd labelling
      indices and higher frequencies of cells in the G0/1 range of DNA content were
      common features of all the cells in HT media, irrespective of their tissue of
      origin; other cycle phases may also be involved, depending on the cell type
      considered. The mechanisms by which cells cope with the HT environment could
      however differ, since only some cell types showed an increase of the 35 kDa
      stress protein found originally in HT EUE cells.

PMID- 7720185
TI  - The increasing effect of some synthetic peptides on luminol-dependent
      chemiluminescence of mouse blood.
AB  - Some synthetic peptides increased the luminol-dependent chemiluminescence of
      mouse blood during phagocytosis. It is suggested that the levels of antimicrobial
      activity of the neutrophil peroxidase system can be raised very quickly (within
      some dozen of seconds) by these peptides. This raises the possibility of finding
      a new approach to the therapy for infectious diseases.

PMID- 7720186
TI  - Activation of phospholipase A2 by 1,25 (OH)2 vitamin D3 and cell growth in
      monocytic U937 and Mono Mac 6 cells.
AB  - Soluble phospholipase A2 activity was characterized in two human monocytic cell
      lines, U937 and Mono Mac 6. The enzyme showed an absolute requirement for Ca++,
      an alkaline pH optimum and Michaelis-Menten kinetics in both cell lines.
      Differentiation of U937 and Mono Mac 6 cells with 1,25 (OH)2 vitamin D3 (10 nM,
      72 h) enhanced PLA2 activity by 82 per cent and 56 per cent, respectively.
      Furthermore, kinetic experiments revealed that enzyme activity increased within 3
      h when cells were brought from the nonproliferative phase of growth to the start
      of a new cycle of cell proliferation. This initial activation of PLA2 could be
      inhibited by cycloheximide and actinomycin D, indicating the requirement of gene
      transcription. Taken together, these results suggest a role of cytosolic, Ca(++)
      dependent PLA2 in differentiation and growth of monocytic cells.

PMID- 7720187
TI  - Guinea pig peritoneal macrophages. Differential effects of lectins on interaction
      with IgG immunoglobulins.
AB  - Guinea pig peritoneal macrophages have on their surface two receptors, one (Fc
      gamma 1/gamma 2 R) binding both guinea pig IgG1 and IgG2 and the second (Fc gamma
      2R) binding only IgG2 immunoglobulins. We have previously shown that treatment of
      macrophages with neuraminidase or glycosylation inhibitors affects, in a
      different way, the binding of guinea pig IgG1, IgG2, and rabbit IgG. In the
      present study we have shown that pretreatment of guinea pig macrophages with
      lectins (Con A, WGA, and PNA) also has a different effect on the interaction of
      the cells with IgG. The lectins increased the binding of guinea pig IgG1, whereas
      rabbit IgG and guinea pig IgG2 were bound with a lower efficiency than in the
      case of control cells. Since sialic acid residues seem to modulate the activity
      of receptors and WGA interacts with sialylated oligosaccharides, we determined
      the IgG-binding characteristics for WGA-pretreated macrophages. We found that the
      increase in IgG1-binding ability was caused by an increase in the value of Kapp,
      but the number of IgG-binding sites was lower than in the control cells. In the
      case of rabbit IgG and guinea pig IgG2 we observed a decrease of both the value
      of Kapp and the number of IgG-binding sites. WGA did not interact directly with
      the Fc gamma receptor. The results of our former papers and the different effects
      of lectins of various specificities described in this paper suggest different
      positions of Fc gamma 1/gamma 2 and Fc gamma 2R in the plane of the macrophage
      membrane in respect to various membrane glycoconjugates.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7720188
TI  - Platelet glycohydrolase activities: characterization and release.
AB  - Granules containing acid hydrolases have been detected in human platelets but
      have not been thoroughly characterized. We have studied the activity and
      characteristics of glycohydrolases present in normal human platelets, evaluated
      their release upon stimulation with thrombin, and assessed the contribution of
      platelet - released lysosomal contents to the glycohydrolase activity present in
      normal serum. Platelets contained a remarkable glycohydrolase activity with a
      prevalence of beta - N-acetylhexosaminidase. All glycohydrolases were released to
      some extent upon stimulation with thrombin and contributed to the glycohydrolase
      activity found in human serum. alpha-Mannosidase and alpha-galactosidase were
      partially inactivated after release by a mechanism as yet undefined. In addition,
      thrombin stimulation affects the intraplatelet isoenzyme pattern of beta-N
      acetylhexosaminidase by producing the appearance of a new form.

PMID- 7720189
TI  - Modulation of phenotypic expression of fibroblasts by alteration of the
      cytoskeleton.
AB  - Several studies indicate that the cytoskeleton may be involved in modulating the
      cellular response to environmental signals. We have studied the role of the
      cytoskeleton in regulating glycosaminoglycan (GAG) synthesis and secretion,
      hyaluronate (HA) endocytosis, the activities of hexoglycosidases, protein
      synthesis and secretion. Fibroblasts were treated with colchicine (1-8 microM)
      and nocodazole (1 or 4 microM) to alter microtubules or cytochalasin B (0.5-4
      microM) to alter microfilaments. Colchicine inhibited GAG synthesis and secretion
      in a concentration-dependent manner. It reduced protein and sulphated GAG
      secretion, while HA secretion was not affected. Concentration-dependent
      disruption of microtubules from the periphery toward the cellular centre with
      nocodazole inhibited only the secretion of GAG. Centrosomal microtubles appeared
      to be required to promote GAG synthesis; intact microtubules promoted the
      transport of secretory products, intercompatmental transport of lysosomal enzymes
      and lysosome maturation, but not protein synthesis and HA secretion. Cytochalasin
      B treatment inhibited, in a concentration-dependent manner, the synthesis and
      secretion of GAGs and proteins, and the endocytosis of HA. Intact microfilament
      meshworks appeared to be required to promote synthesis and secretion of proteins
      and proteoglycans and to contribute to the transmembrane control of receptor
      mediated endocytosis. Drug treatment of concanavalin A (Con A)-stimulated
      fibroblasts inhibited the stimulation of GAG synthesis. It is probable that this
      effect may result, in part, from drug-induced effects on Con A-mediated
      endocytosis.

PMID- 7720190
TI  - Mechanism of citrinin-induced dysfunction of mitochondria. IV--Effect on Ca2+
      transport.
AB  - The effect of citrinin on Ca2+ transport was studied in isolated kidney cortex
      and liver mitochondria, and baby hamster kidney cultured cells. The mycotoxin
      significantly inhibited the activity of 2-oxoglutarate and pyruvate
      dehydrogenases in both kidney cortex and liver mitochondria. Citrinin promoted a
      decrease in the velocity and in the total capacity of Ca2+ uptake, in both
      mitochondria. Apparently, citrinin acts by a mechanism similar to ruthenium red.
      In intact cultured cells, citrinin also had a preferential effect on
      mitochondrial Ca2+ fluxes. Citrinin promoted a marked decrease in the Ca2+ level
      in the mitochondrial matrix, whereas that of the extramitochondiral fraction
      became less affected. All the observed effects were dependent on the citrinin
      concentration.

PMID- 7720191
TI  - Effects of choline and ethanolamine on the synthesis and breakdown of the
      inositol phospholipid (PI) system in Tetrahymena.
AB  - Lower concentrations of choline chloride and ethanolamine (10(-3) M; 10(-5) M)
      increased phosphatidyl inositol (PI), phosphatidyl inositol monophosphate (PIP)
      and phosphatidyl inositol bisphosphate (PIP2) level of Tetrahymena, while higher
      concentrations (10(-2) M) decreased them. These two substances also influenced,
      however in a less obvious way, the transformation of inositol phospholipids. The
      experiments draw attention to the sensitivity of the precursors of the second
      messenger system at a phylogenetically low level.

PMID- 7720192
TI  - Retinoic acid enhances connexin43 expression at the post-transcriptional level in
      rat liver epithelial cells.
AB  - The mechanism by which all-trans retinoic acid (RA) stimulates gap junctional
      intercellular communication (GJIC) in the rat liver epithelial cell line. IAR203,
      was investigated. When RA, at 0.1 microM for 24-48 h, enhanced the dye transfer
      in IAR203 cells (x 1.4), it increased the amount of connexin43 (Cx43) in the cell
      cell contact regions of the plasma membrane, as evidenced by analysis by Western
      blot and by immunofluorescence. It had no effect on the level of Cx43 mRNA.
      Freeze-fracture analysis of the size of gap junctions revealed an increase of the
      proportion of small gap junctions in RA-treated cells. We conclude that, in
      IAR203 cells, RA stimulates GJIC by acting at the post-transcriptional level of
      Cx43 regulation. The possibility that RA acts indirectly on the regulation of
      Cx43 expression, and increases the half-life of Cx43 by inducing adhesion
      molecules is discussed.

PMID- 7720193
TI  - Vanadate enhances insulin-receptor binding in gestational diabetic human
      placenta.
AB  - Although vanadium is found abundantly in animal and plant kingdoms its biological
      effects are not clear. Vanadate compounds have been shown to normalize blood
      glucose levels in streptozotocin treated rats, enhance glucose oxidation and
      improve the sensitivity to insulin by enhanced receptor binding in rat
      adipocytes. The aim of the present study was to investigate the effect of
      vanadate, at high (0-8 mmol l-1) and low (0-1.0 mmol l-1) physiological
      concentrations, on [125I]-insulin binding in the placenta of three groups of
      patients, namely from normal (N) controls, gestational diabetics (GDM) and women
      with risk factors in their medical history for developing diabetes mellitus (RF).
      Vanadate at low concentrations (0.2-0.6 mmol l-1) enhanced the maximal binding 2
      fold in GDM placenta but only increased (up to 1.2-fold) the binding slightly at
      high concentrations (5 mmol l-1). However with placenta from normal or women at
      risk, vanadate increased the [125I]-insulin binding up to 1.2-fold both at low
      and high concentrations. Thus it appears that vanadate augments insulin binding
      in the placenta from women with gestational diabetes mellitus.

PMID- 7720194
TI  - [Report on the first nationwide survey of the distribution of human parasites in
      China. 1. Regional distribution of parasite species].
AB  - A nationwide (Taiwan Province not included) survey of the distribution of human
      parasites in China during 1988-1992 was conducted under the auspices of the
      Ministry of Public Health, with stratified masses randomly sampling. A total of
      2,848 pilot sites in 726 counties with a population of 1,477,742 were surveyed,
      according to unified standard, unified diagnostic method and control quality. The
      overall infection rate of parasites was 62. 632%. Among them, the infection rate
      was over 50% in 17 provinces/autonomous regions/municipalities (P/A/M), over 80%
      in Hainan, Guangxi, Sichuan, Fujian, Zhejiang and Guizhou, being highest in
      Hainan (94. 735%). Altogether 56 species were detected. Centrocestus formosanus
      is reported for the first time at home, Echinochasmus liliputanus and Echinostoma
      angustitestis are reported for the first time at home and abroad. Echinochasmus
      fujianensis is a new species. E. histolytica, G. lamblia, A. lumbricoides,
      whipworm and pinworm were distributed nationwide, while Cysticercus (27 P/A/M),
      Taenia (27), hookworm (26), Balantidium coli (22), Clonorchis sinensis (22),
      Paragonimus westermani (21), H. diminuta (21), Echinococcus (18), H. nana (17),
      Fasciolopsis buski (16), T. spiralis (12) were distributed non-nationwide. A
      preliminary suggestion on intervention of the common and/or most detrimental
      parasitic diseases was submitted, including hydatidosis, taeniasis,
      cysticercosis, clonorchiasis, paragonimiasis, trichinellosis, hookworm disease,
      ascariasis, trichuriasis and enterobiasis.

PMID- 7720195
TI  - [Treatment of 842 cases with cystic echinococcosis of chest].
AB  - 842 cases of thoracic echinococcosis were surgically treated by endocystectomy
      (79%), pneumonectomy (12%), drainage and other operations (9%). Among a total of
      1,010 operations, the mortality was 0.6% (5/807). Of 637 cases received 798
      endocystectomies, the recurrence rate was 4.2% (27/638). Up to 1979, the first
      series of 323 cases were followed-up for 3-20 years, no single case died of
      thoracic echnococcosis. Among the 32 non-operation cases, the mortality was 22.2%
      (6/27) and 9 cases were spontaneously cured. 22 cases were given praziquantel at
      two dosages, Group A received 120-150 mg/kg and Group B received 210 mg/kg in
      divided doses for 5-6 days. The death rate of protoscolices inside the
      operatively removed cystic fluid from the above two groups was 43.1 +/- 9.6% and
      64.2 +/- 3.5%, respectively, while in the untreated Group C 9.2 +/- 2% (P <
      0.01). With total dosage of praziquantel 300 mg/kg in divided doses for 7 days,
      the concentration of praziquantel in patient's blood and cystic fluid was 0.49 +/
      0.075 microgram/ml and 0.006 microgram/ml, respectively.

PMID- 7720196
TI  - Early treatment with artemether and praziquantel in rabbits repeatedly infected
      with Schistosoma japonicum cercariae.
AB  - When rabbits infected with 48-52 Schistosoma japonicum cercariae once every wk
      for 6 times or every other day for 5 times were treated ig with artemether (Art)
      10 or 15 mg.kg-1 on d7 after the first infection, followed by the repeated
      administration of the same dose once every 1-2 wk, a promising effect was seen in
      the groups treated with Art at higher dose. In another group of rabbits with the
      same drug administration regimens of praziquantel (Pra) were also used in early
      treatment, but the initial dose was given on d21 after the first infection. The
      results showed that Pra given at 40 mg.kg-1 in each administration was more
      promising than the lower dose of 30 mg.kg-1 especially in group treated at 2 wk
      intervals. Further study indicated that the presence of adult schistosomes in
      rabbits increased the effect of Pra not only on 21-day-old schistosomule, but
      also on 14-day-old schistosomules. The results suggest that Art and Pra could be
      used in field trial for controlling acute schistosomiasis and decreasing the
      intensity of schistosomal infection.

PMID- 7720197
TI  - [Leishmaniasis in Karamay. XIV. Identification of promastigote isolates from
      naturally infected Phlebotomus major wui].
AB  - Phlebotomus major wui, an anthropophilic species, was predominant among sandflies
      in Karamay, Xinjiang of China. The females of this species collected in the wild
      and houses were detected to be infected with promastigotes. Three isolates of
      promastigotes obtained from P. major wui were inoculated intraperitoneally and
      subcutaneously into normal hamsters or BALB/c mice which developed visceral
      leishmaniasis later. The mean size of amastigotes in hamster viscera (smear
      observation) artificially inoculated with the cultured parasite originated from
      sandfly was significantly smaller than those in control hamster inoculated with
      the cultured Leishmania turanica from great gerbils in situ. The promastigotes
      from P. major wui hardly grew in NNN medium. In addition, 32P labeled gene gp63
      was used as probe to hybridize DNA prepared from L. infantum, L. turanica and
      Leishmania from this sandfly showed that marked homogeneity existed between the
      isolates from P. major wui and L. infantum. At the present time, visceral
      leishmaniasis did not occur in Karamay but cutaneous leishmaniasis (CL) has been
      evidenced. Thus, what is the source of natural infection of P. major wui? Whether
      L. turanica or L. infantum is the pathogen of human CL in this area? These are
      interesting aspects to deal with in the further study.

PMID- 7720198
TI  - [Isolation and purification of glyceraldehyde-3-phosphate dehydrogenase from
      Schistosoma japonicum].
AB  - This paper recommends a simple and easy method to isolate and purify
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Schistosoma japonicum with
      electrophoretic purity. The recovery rate of 56.1% of glyceraldehyde-3-phosphate
      dehydrogenase from S. japonicum extract was achieved by ammonium sulfate
      precipitation, DEAE-cellulose column chromatography and SDS-PAGE. Using SDS-PAGE,
      the presence of one major band in the final purified GAPDH preparation was
      demonstrated. This protein had a MW of 37 kDa. The authors discuss the important
      functions of GAPDH and suggest that this method may be useful in the research of
      the protective immunity of S. japonicum GAPDH in the development of schistosome
      vaccine.

PMID- 7720199
TI  - [Preliminary estimation of malaria transmission potential in areas where
      Anopheles sinensis is the only vector].
AB  - The data, vectorial capacity of Anopheles sinensis in the suburb of Jining city,
      Shandong Province in 1975, in 1980-1984, and the average gland infection rate of
      Anopheles sinensis infected with Plasmodium vivax artificially, were calculated
      by using Macdonald formula (1957). The basic reproduction rates were 4.44, 6.47
      and 4.25 in the years 1975, 1980 and 1981, respectively. In 1982-1984, the rate
      was reduced to 0.69, 0.41 and 0.1, respectively. Since 1982, the incidence rate
      of malaria in the areas was reduced by 80% annually, indicating that the malaria
      transmission had been decreased obviously.

PMID- 7720200
TI  - [Effect of indirect fluorescent antibody test for the diagnosis of amoebiasis].
AB  - Indirect fluorescent antibody test (IFAT) was performed by the method of [symbol:
      see text] (1971) with some slight modifications for the diagnosis of amoebiasis.
      The antigen used was prepared from 48-hour culture of Entamoeba histolytica
      (strains G2, G3, and G5) in LAS diphasic medium and only those amoebae clinging
      the culture were collected. The serum samples or blood drops on filter paper were
      positive by the improved IFAT in all of the 54 cases of amoebic liver abscess and
      the positive reactions of most cases were very marked. Of 23 cases of acute
      amoebic dysentery, 19 were positive, the positive rate being 82.6%. The results
      also show that 42 cases of other diseases and 40 healthy persons were all
      negative.

PMID- 7720201
TI  - [Analysis of electrophoretic patterns of three enzymes of Oncomelania hupensis].
AB  - Allozyme electrophoresis was carried out in starch gel to compare the
      electrophoretic patterns for acid phosphatase (AcP, EC 3. 1. 3.2), peroxidase
      (Po, EC 1.11.1.7) and esterase (Est, EC 3. 1. 1. 1). It was found in this study
      that isoenzymes AcP1, AcP2 and Po1, Po2 were coded by 2 loci respectively and
      they were monomorphic. It is possible to determine 4 loci responsible for
      esterase zymogram, among which isoenzyme Est3 region either consisted of a fast
      (Est3-F) band in the case of Oncomelania hupensis isolated from Anhui, or a slow
      (Est3-S) band in snails from Yunnan. The Rf values of the fast and slow bands
      were 0.362 +/- 0.027 and 0.340 +/- 0.036, respectively. Snails from Yunnan, at
      the upper reaches of the Yangtze River, are proved to be resistant to infection
      with Anhui-Hubei strain of Schistosoma japonicum in the mainland of China, while
      snails from Anhui, at the lower reaches of the Yangtze, susceptible to infection
      with Anhui-Hubei strain of S. japonicum.

PMID- 7720202
TI  - [Effect of artemether on glycogen, protein, alkaline phosphatase and acid
      phosphatase of Schistosoma japonicum].
AB  - When mice infected with Schistosoma japonicum for 32-35 d were treated ig with
      artemether (Art) at a single dose of 300 mg.kg-1 for 24 h, the glycogen content
      of female and male schistosomes decreased significantly with reduction rates of
      about 50%. 72 h after medication, the glycogen reduction rates were 64.1-77.9%.
      Meantime, the protein content of female and male worms was also decreased, the
      reduction rates being 68.1% and 49.3%, respectively. In infected mice treated ig
      with Art at the same dosage for 24 h, the inhibition rates of alkaline
      phosphatase (AKP) activity in female and male worms were 30% and 25%,
      respectively. 72 h later, the AKP activity of female worm was further inhibited
      to 62.3% as compared with the control. Besides, the inhibitory effect of Art on
      acid phosphatase (ACP) activity of female worm was also more apparent than that
      of male worm. 72 h after medication, the respective inhibition rates of ACP
      activity in female and male worms were 75.7% and 47.6%. The results indicated
      that Art might exert its effect on both carbohydrate and protein metabolism of
      schistosomes.

PMID- 7720203
TI  - [Clinical treatment of hepatic and abdominal hydatid cyst by percutaneous
      puncture, drainage and curettage].
AB  - Since 1986, we have treated 302 cases with hepatic and abdominal hydatid cyst
      (361 cysts) by the method of percutaneous puncture, drainage and curettage
      combined with systemic drug and local drug administration with 5 years' follow
      up. The rate of success of percutaneous puncture, aspiration, drainage and
      curettage was 99%. Only one case presented allergic reaction. At 6 months after
      the PPDC, 97.2% (212/218) of the cysts had stopped growth. One year later, 84.4%
      (130/154) of the cysts had disappeared. Five years' follow-up revealed that 77.8%
      (14/18) of the cysts had disappeared. All of the above-mentioned cases have
      recovered except for two cases suffered from recurrence of primary cysts
      resulting from a drop of the cannulas. No serious complications or death had been
      found.

PMID- 7720204
TI  - [Clinical observation on the treatment of 1,627 cases of schistosomiasis
      haematobia with praziquantel of different dosages].
AB  - A total of 1,627 cases of schistosomiasis haematobium had been treated with
      praziquantel of different dosages by the Chinese Medical Team in Mali. The
      patients were all confirmed by egg detection in urine examination and were
      divided into three groups. Group A, 1,187 cases, were each given a single dose of
      40 mg/kg of praziquantel. In Group B, 321 cases, were each treated with 10 mg/kg
      of praziquantel, t.i.d. for two days. In Group C, 119 cases, were each
      administered with one dose of 50 mg/kg of praziquantel. Three months after
      treatment, the urine egg negative conversion rates were 88.5%, 96.6% and 89.1%,
      respectively. It was showed that Group B gave the best efficacy and produced
      fewer side effects, suggesting that the regime of praziquantel treatment given in
      divided doses is better than that given at a single dose.

PMID- 7720205
TI  - [Epidemiology and control of hookworm infection in Fujian province].
AB  - Fujian province has been known to be endemic for mixed hookworm infection with
      Ancylostoma duodenale as the predominant species. The infection rate was 50%
      before 1980. As a result of mass treatment starting from 1980, the infection rate
      was decreased in most areas. And, infection foci were changed from sweet potato
      fields to the banana, sweatcane and asparagus fields where the infection rate
      tended to increase. It is stressed that the current endemic characteristics of
      hookworm infection should be paid more attention in implementing the control
      programme of hookworm infection.

PMID- 7720206
TI  - [Studies on Clonorchiasis sinensis control in Sanshui City, Guangdong province].
AB  - During 1986 to 1988 and 1990 to 1992, Dongyong Township and Guanyuan Township in
      Sanshui City, Guangdong Province were selected as demonstration areas for
      clonorchiasis sinensis control by using measures of repeated examination and
      treatment respectively. After two years' examination and treatment, the
      population infection rates were from 43.6% to 13.2% in Dongyong Township and from
      78.5% to 36.3% in Guanyuan Township. The first intermediate host was Alocimma
      longicornis, and the second intermediate hosts were Parabramis bransula and
      Ctenopharyngodon idellus. The adult worms of Clonorchis sinensis were found in
      the bile ducts of cats, dogs and pigs which may be the reservoir hosts.

PMID- 7720207
TI  - [Establishment of mouse model for Cysticercosis cellulosae].
AB  - Sixty mice were inoculated intravenously with 200-400 Taenia solium eggs
      collected from the gravid proglottides of the adult worm expelled from a
      taeniasis patient after pumpkin seed and areca treatment. The mice were killed
      and dissected 2 months after inoculation, and were found infected with
      Cysticercus cellulosae. These living cysticerci in muscles and lungs were
      elliptic in shape with diameters of 0.3-0.6 cm. The scolex was equipped with two
      rows of hooks and four typical suckers. When the cysticerci were hatched in
      gastric juice and bile for two hours at 37 degrees C the scoleces evaginated
      voluntarily. The results of this study suggest that the mouse can be used as an
      animal model for Cysticercus cellulosae.

PMID- 7720208
TI  - [Studies on the effect of deltamethrin bath treatment of hamsters infected with
      Leishmania donovani for interrupting kala-azar transmission].
AB  - Phlebotomus chinensis were fed respectively on two groups of Cricetulus
      barabensis infected with Leishmania donovani, of which one group had received
      deltamethrin bath and the other was not treated with insecticide bath. The
      results showed that all the sandflies in the former group died within 24 hours,
      while those in the latter group had a high survival rate. Among the 165 sandflies
      examined, 114 (69.1%) became infected. The promastigotes not only developed well
      in the midgut, but also invaded esophagus, pharynx and proboscis. In the control
      group, the mortality of sandflies in 24 hours was 5.1% (3/59). According to the
      data obtained in the present study, the authors consider that insecticide bath
      treatment of infected domestic dogs in endemic villages could be used for
      interrupting kala-azar transmission.

PMID- 7720209
TI  - [Immunity in hookworm infection].

PMID- 7720210
TI  - Nestin mRNA expression correlates with the central nervous system progenitor cell
      state in many, but not all, regions of developing central nervous system.
AB  - Nestin is a recently discovered intermediate filament (IF) gene. Nestin
      expression has been extensively used as a marker for central nervous system (CNS)
      progenitor cells in different contexts, based on observations indicating a
      correlation between nestin expression and this cell type in vivo. To evaluate
      this correlation in more detail nestin mRNA expression in developing and adult
      mouse CNS was analysed by in situ hybridization. We find that nestin is expressed
      from embryonic day (E) 7.75 and that expression is detected in many proliferating
      CNS regions: at E10.5 nestin is expressed in cells of both the rostral and caudal
      neural tube, including the radial glial cells; at E15.5 and postnatal day (P) 0
      expression is observed largely in the developing cerebellum and in the
      ventricular and subventricular areas of the developing telencephalon.
      Furthermore, the transition from a proliferating to a post-mitotic cell state is
      accompanied by a rapid decrease in nestin mRNA for motor neurons in the ventral
      spinal cord and for neurons in the marginal layer of developing telencephalon. In
      contrast to these data we observe two proliferating areas, the olfactory
      epithelium and the precursor cells of the hippocampal granule neurons, which do
      not express nestin at detectable levels. Thus, nestin mRNA expression correlates
      with many, but not all, regions of proliferating CNS progenitor cells. In
      addition to its temporal and spatial regulation nestin expression also appears to
      be regulated at the level of subcellular mRNA localization: in columnar
      neuroepithelial and radial glial cells nestin mRNA is predominantly localized to
      the pial endfeet.

PMID- 7720211
TI  - The ontogeny of glutamate receptors in rat barrel field cortex.
AB  - The ontogeny of N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid
      receptors in rat barrel field cortex were characterized using receptor
      autoradiography. NMDA receptors showed a different pattern of development than
      that of non-NMDA receptors recognizing quisqualate (QUIS sites). During the first
      14 days, high densities of QUIS sites were localized in barrel centers forming a
      sensory map of the rat whisker pad. After that time, the density of QUIS sites in
      barrel centers decreased so that the pattern was no longer apparent by postnatal
      day 21. In contrast to QUIS sites, NMDA sites did not exhibit a somatotopic
      pattern until postnatal day 21, when the lower density of sites in barrel septa
      formed an outline of barrel centers. At all ages examined, the density of NMDA
      sites did not differ significantly between barrel centers and surrounding cortex.
      Of the non-NMDA receptors examined in the postnatal day 10 old rat, both
      metabotropic sites and the NNKQ sites, which are [3H]glutamate binding sites that
      are not displaceable by NMDA, kainate or QUIS, showed a pattern of higher
      densities in barrel centers than surrounding tissue, whereas AMPA sites exhibited
      a complementary pattern. [3H]Glutamate binding to metabotropic sites was not
      significantly displaced by QUIS, whereas both NNKQ sites and metabotropic sites
      were potently blocked by the metabotropic agonist trans-ACPD. These results
      suggest that the NNKQ sites are low affinity QUIS metabotropic receptors, which,
      due to their high density in the immature barrel field, are in a position to
      influence barrel formation.

PMID- 7720212
TI  - In vivo electrophysiological maturation of neurons derived from a multipotent
      precursor (embryonal carcinoma) cell line.
AB  - The multipotent embryonal carcinoma (EC) P19 cell line differentiates into
      neurons, glia and smooth muscle following exposure to retinoic acid (RA). RA
      induced differentiation is irreversible and the neurons that develop are
      abundant, post-mitotic, and survive for prolonged periods in culture or when
      grafted into the CNS of adult rats. Striatal slices containing grafted P19 cells
      were studied with intracellular recording and labelling techniques to examine the
      development of electrophysiological and morphological properties of P19-derived
      neurons over a period of 6 to 120 days after grafting into ibotenic acid lesioned
      striatum. Cells from 1-week-old grafts had a range of immature
      electrophysiological characteristics including unstable resting membrane
      potentials (RMP's) and very high membrane input resistances (Rin's). Many were
      not able to produce action potentials (AP's). In contrast, the majority of cells
      recorded from 2- and 3-week-old grafts had stable RMP's, moderate Rin's, and were
      able to produce regenerative AP's. In grafts over 4 weeks of age, the majority of
      P19-derived neurons had mature neuronal electrophysiological characteristics
      including RMP's of -60 mV, Rin's of 100-300 M omega, and overshooting AP's.
      Morphologically, P19 derived neurons increase in soma size from 12-15 mu in
      diameter in 7-14-day-old grafts, to 25-35 mu in diameter in grafts 50-120 days
      old. Developing neurons exhibited a variety of morphotypes with increasingly
      complex processes and lengths of process extension. Our results demonstrate a
      developmental progression of the electrophysiology of P19-derived neurons,
      culminating in mature characteristics closely resembling those of adult rodent
      hippocampal or cortical pyramidal neurons. The ability to easily alter these
      cells genetically provides a powerful model for addressing issues specific to
      neuronal development.

PMID- 7720213
TI  - Germinal matrix microvascular maturation correlates inversely with the risk
      period for neonatal intraventricular hemorrhage.
AB  - The risk period for intraventricular hemorrhage (IVH) of the preterm neonate is
      the first 3-4 postnatal days. For infants of < 34 weeks' gestation, this risk
      period is independent of gestational age. We hypothesized that this risk period
      is attributable to the perinatal induction of maturation of the germinal matrix
      microvasculature and tested this hypothesis by examining changes in the classical
      ultrastructural features of the blood-brain barrier over the first ten postnatal
      days in the newborn beagle model for neonatal IVH. Newborn beagle pups (n = 6)
      were anesthetized and systemically perfused and the brains were removed and
      prepared for electron microscopic examination. Examination of electron
      micrographs from the germinal matrix of animals on the first, fourth and tenth
      postnatal days demonstrated no difference in perimeter lengths and capillary and
      endothelial cell areas; in contrast, luminal areas significantly decreased across
      postnatal age (P = 0.04). Significant increases were found in basement membrane
      area between days 1 and 4 (P = 0.01) and tight junction length (day 1 vs. day 10,
      P = 0.02). In addition, on day 1, 19% of germinal matrix capillary perimeter was
      determined not to be covered by supporting cell processes, while by day 10, only
      5% was bare. In contrast, the microvessels of the white matter exhibited no
      changes in these parameters during these three time points. These studies are
      consistent with the concept that basal lamina deposition and organization precede
      increases in endothelial cell tight junction formation and coverage by supporting
      cells.

PMID- 7720214
TI  - Appearance of neuropeptides and NADPH-diaphorase during development of the
      enteropancreatic innervation.
AB  - Pancreatic ganglia are formed by neural crest-derived precursors, are innervated
      by enteric neurons, and contain neuropeptides. In addition, the enzyme NADPH
      diaphorase is located in a subset of enteric and pancreatic neurons. The
      expression of neural markers (GAP-43 and NC-1), neurotransmitter-related markers
      (including neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), gastrin
      releasing peptide (GRP), galanin (GAL), dopamine beta hydroxylase (DBH),
      substance P (SP), calcitonin gene-related peptide (CGRP)), and NADPH-diaphorase
      was studied in the fetal and neonatal rat gut and pancreas (E12-P28) in situ and
      in vitro. NC-1, GAP-43 and DBH-immunoreactive cells were found in the primordial
      stomach on day E12, and in the pancreas on day E13, along with NPY in endocrine
      cells. Pancreatic NPY-immunoreactive neurons were detected by day E18. CGRP was
      seen in the foregut at day E12 but not in the pancreas until day E14. Other
      neuropeptides (SP, GAL, GRP and VIP) all appeared in the foregut earlier than in
      the pancreas. NADPH-diaphorase activity was first found in situ in foregut
      neurons on day E13, and in the pancreas on day E14, but seen in explants a day
      earlier. These observations show that development of neurons occurs earlier in
      the gut than in the pancreas, and that NADPH-diaphorase activity appears earlier
      than the immunoreactivities of the neuropeptides.

PMID- 7720215
TI  - Dark-rearing fails to affect the basal dendritic fields of layer 3 pyramidal
      cells in the kitten's visual cortex.
AB  - The development of the cat's visual cortex is incomplete at birth and is
      influenced by the cat's early visual experience. We have previously demonstrated
      that the basal dendritic fields of layer 3 pyramidal cells grow substantially
      during the first 5 weeks after birth and that stripe-rearing affects their
      orientation. In this paper we determined the effects on these dendritic fields of
      visual deprivation (dark-rearing) during the first 3 months of life. The visual
      cortices of both normally reared and dark-reared cats were impregnated by the
      Golgi method, sectioned in the tangential plane and counterstained. The basal
      dendritic fields of completely impregnated pyramidal cells from layer 3 were
      drawn with the aid of a camera lucida, and compared in terms of number and length
      of primary dendrites, branching, size, elongation, and distribution of dendritic
      field orientations. Surprisingly, we observed no significant differences in any
      parameter measured. Thus, although stripe-rearing can specifically alter the
      orientation of the dendritic fields of the layer 3 pyramidal cells, and dark
      rearing has been shown by others to alter the size of layer 4 stellate cells,
      dark-rearing failed to affect the dendritic fields of layer 3 pyramidal cells.

PMID- 7720216
TI  - Nicotine administration differentially affects gene expression in the maternal
      and fetal circadian clock.
AB  - Exposure to nicotine by active and passive cigarette smoke is a common public
      health problem. Recent studies have demonstrated that human fetuses are also
      exposed to significant levels of nicotine and that there is a five-fold increase
      in the incidence of Sudden Infant Death Syndrome among infants born to smoking
      mothers. We examined the effect of nicotine administration and expression of the
      immediate early gene c-fos in the maternal and fetal rat brain by in situ
      hybridization. Nicotine injection (1 mg/kg s.c.) on embryonic day 20 (E20)
      induced detectable c-fos mRNA in the maternal habenula and hypothalamic
      paraventricular nucleus whereas, in the fetal brain, c-fos was induced in both
      these structures and also in the suprachiasmatic nucleus (SCN). Nicotine-induced
      c-fos expression in the fetal SCN was confirmed by Northern analysis and found to
      return to near basal levels by 3 h post-injection. These responses were blocked
      by pre-administration of mecamylamine, indicating that the effect of nicotine is
      mediated through the cholinergic system. Investigation of the development of this
      response revealed that nicotine failed to induce c-fos expression in the SCN on
      E16, caused minimal expression on E18, robust expression on E20 and postnatal day
      0 (P0), and no expression on P2 or thereafter. These observations suggest that an
      alteration in the composition of the nicotinic receptors (nAChR), or the
      subsequent intracellular responses leading to c-fos expression, occurs in the SCN
      during the perinatal period. Induction of c-fos mRNA in the SCN by light has been
      associated with phase-shifts of the circadian system, however, the behavioral
      consequences of the transient sensitivity of the fetal and neonatal SCN to
      nicotine administration and the consequences for maternal-fetal entrainment
      remain to be directly determined.

PMID- 7720217
TI  - Sex-specific effects of prenatal stress on hypothalamic-pituitary-adrenal
      responses to stress and brain glucocorticoid receptor density in adult rats.
AB  - Previous research indicates that the offspring of dams exposed to stress during
      late gestation show altered hypothalamic-pituitary-adrenal (HPA) responses to
      stress. However, the results are inconsistent and a review of the literature
      suggests that the effects may differ depending upon the gender of the offspring.
      In the present study, we measured plasma adrenocorticotropin (ACTH) and
      corticosterone (B) levels prior to, and at 0, 20, 40 and 70 min following
      restraint stress in catheterized adult male and female offspring of dams stressed
      in the last week of gestation (i.e. days 15-19 of gestation). Prenatal stress
      significantly increased both plasma ACTH and B levels in response to restraint,
      but only in females; male offspring were largely unaffected. In addition, plasma
      corticosteroid-binding globulin (CBG) levels were significantly increased in
      prenatally-stressed females, but not in males. Despite these differences in
      plasma CBG, estimated free B levels following restraint were also significantly
      elevated in prenatally-stressed females. We then examined glucocorticoid receptor
      binding in a variety of forebrain structures. Prenatal stress had no effect on
      glucocorticoid receptor density in the hypothalamus or hippocampus in either
      males or females. Differences in glucocorticoid receptor density across groups
      were observed in the septum, frontal cortex, and amygdala. However, the pattern
      of observed differences across the groups was not consistent with the pattern of
      hormonal differences. In summary, the effect of prenatal stress on HPA function
      is substantially more marked in females than in males. Interestingly, a similar
      pattern of effects on HPA activity has been reported for prenatal alcohol
      exposure.

PMID- 7720218
TI  - Ontogeny of peripheral-type benzodiazepine receptors in cultured astrocytes and
      brain from rat.
AB  - Peripheral-type benzodiazepine receptors (PBRs) in brain are primarily localized
      within astroglial cells, and the existence of PBR subtypes have been suggested.
      In the present study the ontogeny of PBRs labeled with [3H]Ro5-4864 and [3H]PK
      11195 in cultured astrocytes was compared to their postnatal in-vivo development.
      The density of [3H]Ro5-4864 binding sites in cultured astrocytes from rat cortex
      progressively increased from 1- to 3-week-old cultures and did not change further
      in 5- and 8-week-old cultures. The density of [3H]PK 11195 binding sites
      progressively increased from 1- to 5-week-old cultures. The density of [3H]PK
      11195 binding sites exceeded the density of [3H]Ro5-4864 binding sites by 40-50%
      in 2-, 5- and 8-week-old cultures. The affinity of the PBR ligands for the
      receptor sites was increased by 3- to 4-fold from the first to the second week in
      cultures, and did not change thereafter. A similar developmental pattern of PBRs
      was observed in rat cortex, except that: first, the difference between the Bmax
      of [3H]PK 11195 and [3H]Ro5-4864 was already apparent in postnatal-week-1 and
      persisted with maturation; second, the high affinity of the ligands for the
      receptor sites was apparent from postnatal-week-1 and did not change with
      maturation. Age-related differences in the ratio between the density of PBRs in
      astrocytes and rat cortex were also observed. These results lead us to suggest
      that the development of PBRs in vivo during the first postnatal week is more
      rapid than the development of the receptors in vitro during the first week in
      culture. Subsequently, the increased ratio between the density of PBRs in
      cultured astrocytes and brain with maturation indicates the predominantly
      astrocytic localization of these receptors. The finding that the density of
      [3H]PK 11195 binding sites in cultured astrocytes and in rat brain cortex is
      usually 40-50% greater than the density of [3H]Ro5-4864 binding sites further
      supports the existence of PBR subtypes.

PMID- 7720219
TI  - IGF-1 influences olfactory bulb maturation. Evidence from anti-IGF-1 antibody
      treatment of developing grafts in oculo.
AB  - Recent studies have indicated that both insulin-like growth factor-1 (IGF-1) and
      IGF-1 receptor mRNA are abundant in developing and adult olfactory bulbs, and
      that IGF-1 receptor mRNA is abundant in the prenatal cerebral cortex. To examine
      the potential role of IGF-1 in development of a central nervous system region
      rich in IGF-1 and its receptor (the olfactory bulb), as compared to one in which
      IGF-1 is less abundant (the cerebral cortex), tissue pieces of these two central
      nervous system areas from E15-E17 rat fetuses were transplanted into the anterior
      chamber of the eye of adult host rats. The transplants were treated with either a
      total of 300 ng truncated IGF-1, two different IGF-1 polyclonal antisera, two
      different non-immune sera, a total of 15 micrograms IGF binding protein-1, or
      vehicle alone. Treatments were administered by preincubation just prior to
      grafting and by 5 microliters injections into the anterior chamber on days 5, 10
      and 15 postgrafting. Olfactory bulb grafts treated with either of the two IGF-1
      antisera grew significantly larger than grafts receiving any other treatment. No
      enhancement of graft size was seen in E16-E17 parietal cortex grafts after IGF-1
      antibody treatment. Immunohistochemical studies revealed no difference between
      the treatments with regard to glial fibrillary acidic protein-, tyrosine
      hydroxylase- or neurofilament-immunoreactivity within the olfactory bulb grafts.
      Since, in the olfactory bulb the presumed reduction of endogenous IGF-1 achieved
      by antibody treatment caused enhanced growth, we suggest that the presence of
      appropriate endogenous levels of IGF-1 in this area induces maturation. This
      mechanism is not operative in all brain areas since it was not seen in cortex
      cerebri grafts. Thus, endogenous IGF-1 appears to influence brain development in
      a regionally specific manner.

PMID- 7720220
TI  - Trophic effect of collicular proteoglycan on neonatal rat retinal ganglion cells
      in situ.
AB  - Naturally occurring neuronal death is widespread in the central nervous system of
      mammals. To date, the causes and mechanisms of such death are poorly understood.
      A major hypothesis is that developing neurons compete for limited amounts of
      trophic factor(s) released from their target centres as in the case of the
      peripheral nervous system and nerve growth factor. The present study aims to test
      this 'trophic hypothesis' in the mammalian central nervous system. In the rat,
      more than 50% of retinal ganglion cells die in the early post-natal period.
      Schulz and coworkers [57] purified a potential trophic agent from their major
      target, the superior colliculus, which was identified as a 480 kDa chondroitin
      sulfate proteoglycan. This proteoglycan or control solutions were injected into
      the eyes of rat pups during the post-natal part of the period of naturally
      occurring ganglion cell death. It was found that the collicular proteoglycan
      prevented the death of a significant number of the ganglion cells that would
      normally have been lost over a post-injection period of one or two days. The
      effect of the proteoglycan was dose- and time-dependent. These results support
      the notion that trophic interactions are a determining factor in the survival of
      retinal ganglion cells during the period of naturally occurring cell death. It is
      also the first time that a proteoglycan has been shown to possess neurotrophic
      properties in situ.

PMID- 7720221
TI  - Rapid serotonergic fiber sprouting in response to ibotenic acid lesion in the
      striatum and hippocampus.
AB  - Serotonergic (5-HT) sprouting occurs after damage of neighboring 5-HT or non-5-HT
      fibers. The sprouting signals appear to originate from the target tissue where
      neural trophic factors are secreted. In order to determine the cellular source of
      the trophic signal we currently report that removal of local neurons with a
      neurotoxin, ibotenic acid (IB), triggered a vigorous sprouting of 5-HT fibers in
      the striatum as early as 3 days after the lesion, which lasted throughout the
      entire length (21 days) of our study. The 5-HT fiber density in the injection
      site increased 10-fold in the striatum compared to the contralateral side, and
      the density of 5-HT varicosities increased 4-fold of normal. The 5-HT level in
      the striatum correspondingly increased on the lesion side. Three clear
      morphological concentric zones were formed by the lesion: acellular, aneuronal
      and outer zones. These zones represent the characteristic reorganization of
      astrocytes and neurons following an injection of IB. Devoid of any cells, the
      small acellular zone in the center of the injection site contained few 5-HT
      fibers. Devoid of neurons, the aneuronal zone contained reactive astrocytes and
      an abnormally high density of 5-HT fibers with increased staining of S-100.
      Containing neurons and astrocytes, the outer zone had a normal 5-HT fiber
      density. The induced 5-HT sprouting in the aneuronal zone strongly suggests that
      local neurons could provide a trophic factor, but that astrocytes would be the
      most plausible candidate. This is not an isolated case, IB injections in the
      hippocampus also induce a similar phenomenon.

PMID- 7720222
TI  - Transient expression of estrogen receptor-immunoreactivity (ER-IR) in the layer V
      of the developing rat cerebral cortex.
AB  - Occurrence of estrogen receptor-immunoreactivity (ER-IR) in the cerebral cortex
      was examined in neonatal and adult rats. In newborn rats of postnatal day 1 (=
      day of birth) and postnatal day 5 (PD1 and PD5, respectively), ER-IR was not
      evident in the neocortex. On postnatal days 7, 10 and 13 (PD7, PD10 and PD13
      respectively), a group of cells with distinct ER-IR appeared in the layer V of
      the auditory cortex. At the PD10, weak but specific ER-IR were also appeared in
      the somatosensory and the visual cortices. Among these areas, the ER-IR positive
      neurons occurred most frequently in the auditory cortex at PD10 rats. By
      examination of adjacent sections, one stained with Cresyl violet and the another
      stained with acethylcholinesterase (AChE) histochemistry, it was revealed that
      the region with ER-IR at PD7 to PD13 was limited to layer V of the neocortex.
      These signals, however, disappeared at PD15. In layer II of the neocortex, on the
      other hand, weak ER-IR signals were detected throughout the area sporadically at
      PD21 and in adults. The ER-IR detected transiently in the auditory cortex by the
      antiserum might contribute to maturation and establishment of the neurons of the
      rat auditory circuit.

PMID- 7720223
TI  - Biochemical markers of myocardial damage.
AB  - OBJECTIVE: To assess various biochemical markers of myocardial damage. METHODS
      AND RESULTS: Before routinely using any test as a biochemical marker of
      myocardial damage, the published evidence for its diagnostic utility must be
      critically assessed. Such assessment includes receiver operator curve (ROC) curve
      analyses, confidence interval estimates of claimed sensitivity and specificity
      values, and the effects of testing in serial and parallel modes. It is also
      necessary to establish the test's rule-in (high specificity) and rule-out (high
      sensitivity) decision thresholds that may vary with time after the onset of
      symptoms. The spectrum of ischemic heart disease includes acute (sudden death,
      non-Q- and Q-wave infarctions) and chronic (stable, unstable, and variant angina)
      conditions. Biochemical markers of myocardial damage are of most value in the
      diagnosis of acute ischemic heart disease, although increasingly some of these
      markers are being found to possess a prognostic value in chronic ischemic heart
      disease. The markers of enzymatic activity include aspartate aminotransferase,
      creatine kinase (together with isoenzymes and isoforms), and lactate
      dehydrogenase and isoenzymes. Creatine kinase isoenzyme-2 may also be measured
      immunologically, and this type of assay is in increasing use both because of its
      speed and because its blood levels rise earlier than the corresponding
      activities. The commercially available nonenzymatic markers are myoglobin and
      troponin T; troponin I is expected to become available in late 1995. While
      myoglobin is a nonspecific indicator of myocardial damage, its diagnostic value
      is due to its early appearance in blood. Troponin T is more cardiac specific, but
      the published data appears to suggest that the cardiac specificity of troponin I
      is superior. Troponin levels become abnormal at about the same time after the
      onset of symptoms as mass assays of creatine kinase isoenzyme-2; therefore, they
      are not useful as early markers of myocardial damage. CONCLUSION: The
      availability of these nonenzymatic markers of myocardial damage must force a
      reassessment of the continued use of the enzymatic markers. Are they necessary,
      and if so, which ones should be retained?

PMID- 7720224
TI  - Lipid and lipoprotein genetic variability: an important contribution from the
      French health examination centers.
AB  - OBJECTIVE: To assess lipid and lipoprotein genetic variability in the French
      Population. METHODS: Many health examination centers are covering a great part of
      France (700,000 individuals are examined in 54 centers every year). Each citizen
      has the right to have a personal examination every 5 years. This unique system
      was modified in 1992, and we are presenting our 25-year experience focusing on
      the results we have more recently obtained in the lipid and lipoprotein field.
      RESULTS: First of all, the 600 items of information collected on every patient
      coming to our Center give us the data and facilitate the development of the
      theory of reference values. Having mastered the analytical variations, we studied
      the biological variations. Age, sex, overweight, tobacco, alcohol, and drugs are
      the main factors we should control for obtaining reference values. More recently,
      the genetic part in the production of reference values has become of greater
      importance, particularly for apolipoproteins. Apolipoprotein E is an important
      lipoprotein for which the two frequent mutations influence the level of
      circulating Apolipoprotein E. The risks linked to these alleles are also very
      different in cardiovascular disease and extremely important (for epsilon 4) in
      Alzheimer's Disease. Apolipoproteins B and A-IV also have interesting
      polymorphisms, but currently have no systematic applications in clinical
      chemistry. The familial recruitment we have in Nancy also permitted us to
      constitute a large tool "La Cohorte Stanislas." CONCLUSION: The thousand families
      recruited will be followed for 10 years. It is an open tool for collaboration.

PMID- 7720225
TI  - Fluorescence-activated cytometry cell sorting based on immunological recognition.

PMID- 7720226
TI  - An epidemiological perspective on cancer screening.
AB  - OBJECTIVE: To provide an epidemiological perspective on cancer screening. METHODS
      AND RESULTS: For screening to be applicable as public health policy, the disease
      has to be an important health problem, there has to be evidence that early
      detection results in improved outcome, that adequate facilities for diagnosis,
      therapy, and subsequent management of true and false positives are available,
      that screening is acceptable to the target groups, and that programs are cost
      effective in the population. Although it is relatively easy to demonstrate that
      screening results in earlier detection of cancer, survival is a biassed measure
      of its effectiveness. The only valid design to study the efficacy of screening is
      the randomized trial. Cervical cancer screening was introduced before these
      requirements were recognized. There is, however, good evidence of its
      effectiveness; the challenge is to make programs cost effective. For breast
      cancer, studies show little or no evidence of effectiveness of mammography
      screening in women age 40-49. For women age 50-69, there is good evidence of
      effectiveness in trials comparing screening with no screening. These support the
      introduction of population-based programs for this age group. The challenge is to
      put the research results into practice to ensure cost-effective programs. For
      colo-rectal cancer, there is some evidence that both screening sigmoidoscopy and
      the fecal occult blood test will reduce mortality. It is not clear, however,
      whether programs using either or both these tests will be cost effective. For
      lung cancer, there is good evidence of no benefit for screening. For ovarian,
      prostate, mouth, and skin cancer, although early detection has been demonstrated,
      there is no evidence of reduction in mortality in the target groups; indeed,
      prostate screening could result in lowering the overall quality of life.
      CONCLUSION: Screening, which offers a fairly rapid return from appropriate
      investment, should remain part of our armamentarium for cancer control.

PMID- 7720227
TI  - Urinary 6 beta-hydroxycortisol in humans: analysis, biological variations, and
      reference ranges.
AB  - OBJECTIVE: To evaluate methods for analysis, biological variation, and reference
      ranges for 6 beta-hydroxycortisol in urine. METHODS: The urinary level of 6 beta
      hydroxycortisol (6 beta-OHF) was measured by reversed-phase high performance
      liquid chromatography. RESULTS: The method was accurate and precise, as indicated
      by a recovery rate of 92-95% and less than 5.5% and 6.6% of coefficient of
      variation for within-run and between-run assay, respectively. The reference range
      of urinary 6 beta-OHF was 187-1245 nmol/day in adults (20-60 years) and 103-915
      nmol/day in the elderly (> 61 years). No significant day-to-day intrabiological
      variation was observed in a 5-day period. Diurnal rhythms of urinary 6 beta-OHF
      and urinary free cortisol (UFC) were quite parallel to each other, so that the
      ratio of 6 beta-OHF to UFC remained constant through the day. CONCLUSION: An
      early morning urine specimen can provide the urinary ratio of 6 beta-OHF to UFC
      as adequately as that determined from 24-h specimen.

PMID- 7720228
TI  - Interference in triiodothyronine (T3) analysis on the Immuno 1 Analyzer.
AB  - OBJECTIVE: To evaluate the interference in Triiodothyronine (T3) analysis on the
      Immuno 1 Analyzer. METHODS: We analyzed 686 samples for T3 using the Miles
      Technicon Immuno 1 Analyzer. We compared the results of 318 samples with those
      given by radioimmunoassay (RIA) and the remaining 368 results with those given by
      the Ciba-Corning ACS 180 analyzer. RESULTS: On the Immuno 1 correlated with those
      by RIA or chemiluminescence immunoassay. However, results on eight patients by
      the Immuno 1 method were anomalously elevated. We attempted to find and eliminate
      the cause of the interference on the Immuno 1. Although the method uses an
      alkaline phosphatase labelled T3 analog and fluoresceinated monoclonal antibody,
      serum binding of fluorescein or alkaline phosphatase did not appear to be the
      major causes of the interference. Ethanol extraction of samples followed by
      reconstitution in zero calibrator was the only reliable way to eliminate the
      interference. CONCLUSION: The Immuno 1 assay was more prone to interference than
      other methods. Until it is reformulated, we recommend that users assay ethanol
      extracts of samples with unexpectedly high T3.

PMID- 7720229
TI  - Assessment of the antielastase activities in bronchoalveolar lavage fluid: effect
      of assay buffer ionic strength.
AB  - OBJECTIVE: To evaluate the effect of assay buffer ionic strength on assessment of
      the antielastase activities in bronchoalveolar lavage fluid. METHOD: An improved
      assay protocol in which elastase (in Tris-HCI buffer) is added to increasing
      volumes of test samples (made up to equal volume with phosphate-buffered saline)
      was used. RESULTS: The percent NE activity inhibited by BALF decreased with
      increasing NaCl concentration of the buffer. Inhibition of pancreatic elastase
      (PE) was not affected. One hundred percent inhibition of NE by pure AAT and SLPI
      standards occurred at molar ratios of 0.91 +/- 0.03 for AAT-to-NE and 0.83 +/-
      0.02 for SLPI-to-NE when assayed in buffer with < or = 0.15 mol NaCl/L, compared
      to ratios of 0.99 +/- 0.02 and 1.06 +/- 0.02, respectively, for assays in buffers
      with 0.50-1.00 mol NaCl/L (p < 0.05 for AAT-to-NE; p < 0.02 for SLPI-to-NE). The
      AAT-to-PE molar ratio at 100% inhibition of PE was not affected. Assays in buffer
      with < or = 0.15 mol NaCl/L indicated that 86.9 +/- 4.1% of AAT and 100.9 +/-
      4.9% of SLPI in BALF were active against NE, while assays in buffer with 0.50
      1.00 mol NaCl/L showed that 84.4 +/- 3.5% of AAT and 81.6 +/- 5.9% of SLPI
      present were active. AAT inhibited NE and PE equally only in buffer with 0.50
      1.00 mol NaCl/L. CONCLUSIONS: The results of assays of BALF antielastase
      activities depend on the assay buffer NaCl concentration, which may account for
      the conflicting reports in the literature. The buffer with 0.50-1.00 mol NaCl/L
      appear to be optimal for valid quantitation of anti-NE activities in BALF.

PMID- 7720230
TI  - Type 1-prophospholipase A2 propeptide immunoreactivity is released from activated
      granulocytes.
AB  - OBJECTIVE: To establish a ELISA assay to measure release of type 1-phospholipase
      A2 propeptide from activated granulocytes. Human type 1-prophospholipase A2 (1
      proPLA2) is biosynthesized and stored as inactive zymogen. Activation involves
      tryptic-like cleavage at the N-terminus, with equimolar release of the
      heptapeptide DSGISPR. METHODS: Using antibodies directed to the carboxyterminus
      of synthetic DSGISPR we developed a sensitive solid-phase ELISA specific for the
      released propeptide that accurately reports the activation of 1-proPLA2. The
      presence of the 1-proPLA2 precursor itself can be determined by trypsinization of
      the sample and subsequent assay for free DSGISPR. RESULTS: Using this ELISA, we
      demonstrated the presence of immunoreactive DSGISPR and its 14 kDa 1-proPLA2-like
      precursor in human granulocytes, but their absence in human macrophages and
      lymphocytes. Stimulation of cultured granulocytes with 1 pM of TNF alpha or GM
      CSF caused rapid release of DSGISPR and precursor into the surrounding medium.
      The immunoreactive signal coeluted with standard synthetic DSGISPR on G50
      Sephadex chromatography. CONCLUSION: Release of DSGISPR immunoreactivity appears
      to be a specific consequence of granulocyte activation of potential relevance to
      the clinical pathophysiology of conditions like acute lung injury.

PMID- 7720231
TI  - Specific heparin preparations interfere with the simultaneous measurement of
      ionized magnesium and ionized calcium.
AB  - OBJECTIVE: To determine whether heparin anticoagulants used for analysis of whole
      blood ionized calcium would influence the measurement of ionized magnesium.
      METHODS: The effects of zinc heparin, lithium heparin, and electrolyte-balanced
      heparin on the simultaneous measurement of ionized magnesium and ionized calcium
      in serum were determined using ion selective electrodes. RESULTS: Time-dependent
      biases in ionized magnesium and calcium concentrations were apparent with zinc
      heparin but not with lithium or electrolyte-balanced heparin. Ionized magnesium
      and calcium concentrations were more significantly influenced by volume-dependent
      changes in zinc heparin potency than with lithium or electrolyte-balanced
      heparin. CONCLUSION: Zinc heparin produces a significant positive bias in the
      simultaneous determination of ionized magnesium and ionized calcium
      concentrations.

PMID- 7720232
TI  - Prolonged survival in pyruvate carboxylase deficiency: lack of correlation with
      enzyme activity in cultured fibroblasts.
AB  - OBJECTIVE: To report the clinical history and laboratory evaluation of a patient
      presenting with lactic acidosis secondary to pyruvate carboxylase deficiency.
      METHODS AND RESULTS: Enzyme analysis of cultured skin fibroblasts revealed 2-5%
      of normal pyruvate carboxylase activity. Although most patients with this
      condition die in early infancy, this child has survived to age 8-1/2 years, with
      only occasional episodes of metabolic acidosis, usually responding rapidly to
      intravenous hydration and bicarbonate. Despite having a seizure disorder and
      moderate mental retardation, he continues to thrive and make progress in his
      acquisition of motor and language skills. Of the 35 patients described in the
      literature with pyruvate carboxylase deficiency, only two other patients have
      lived beyond 5 years of age. CONCLUSION: There does not seem to be a correlation
      of prolonged survival with residual pyruvate carboxylase activity on assay of
      cultured fibroblasts. Possible explanations for this patient's prolonged survival
      include tissue heterogeneity, increased residual enzyme activity in vivo, or
      partial stabilization of the enzyme by supplemental biotin.

PMID- 7720233
TI  - Elevation of activity of creatine phosphokinase (CK) and its isoenzymes in the
      newborn is associated with fetal asphyxia and risk at birth.
AB  - OBJECTIVE: To investigate the relationship of creatine phosphokinase and its
      isoenzymes with fetal asphyxia and risk at birth. METHODS: Thirty-five pregnant
      women with high-risk pregnancy were studied. RESULTS: In 21 patients, fetal
      distress was diagnosed by interpretation of the fetal heart rate tracing (FHR).
      The remaining 14 women, having normal fetal cardiotocography, were considered as
      the control group. Total CK and its isoenzymes activity was measured in cord sera
      and 24 h after birth in peripheral blood. Abnormal FHR patterns correlate well
      with elevated enzyme activities. Total CK and its isoenzymes (CK-MM, CK-MB, and
      CK-BB) exhibited higher values in asphyxiated infants as compared to normal
      neonates. Electrocardiographic ischemia occurred in seven newborns who had
      elevated CK-MB and CK-BB levels, both at birth and within 24 h postpartum.
      Chromatographic study showed in normal neonates that the predominant isoenzyme
      was CK-MM, whereas CK-BB activity was negligible. In the newborns with abnormal
      FHR, CK-MB and CK-BB were increased with predominance of CK-MB. CONCLUSIONS:
      Antepartum fetal distress is associated with release of CK-BB, and particularly
      CK-MB; therefore, these biochemical markers may indicate either brain or
      myocardial damage.

PMID- 7720234
TI  - Evaluation of an immunoturbidimetric assay for hemoglobin A1c.

PMID- 7720235
TI  - Laboratory evaluation of von Willebrand disease.

PMID- 7720236
TI  - On-line computer pharmacokinetics program: lessons learned from its failure.
AB  - Decision support computer technology (DST) embedded in laboratory or hospital
      information systems has great potential but has rarely been successful. Through
      studying a pharmacokinetic program that automatically extracted data without
      requiring manual data entry, we have identified several barriers to the
      successful implementation of DST. Manual data entry is a major barrier, but so is
      the entry of erroneous data such as heights, weights, drug dosing times, and
      specimen collection times. In such a system, unanticipated changed modes of
      clinical practice and software changes in the system's component modules can be
      incompatible with the decision-support program, necessitating software revisions.
      We also noted that clinicians increased their ordering of laboratory tests and
      changes in drug doses but without improvement in patients' outcomes. This
      suggests that information output from the program can be misinterpreted by
      clinicians. In summary, DST programs should be validated in an actual working
      environment.

PMID- 7720237
TI  - Clinical capillary electrophoresis.
AB  - Capillary electrophoresis is a relatively new analytical technique that has begun
      to have an impact in the clinical laboratory, both for routine analyses and for
      those that are more esoteric. Its potential for automated, rapid, high-efficiency
      separations makes it appealing as a replacement for some of the more labor
      intensive assays carried out in electrophoretic gels and as a complement to
      companion techniques such as HPLC. Among the many attractive characteristics of
      this technology is its versatility for analyses of a diverse spectrum of
      analytes, ranging from small organic ions to macromolecular protein complexes or
      DNA. The focus of this commentary is to familiarize the clinical scientist with
      the instrumentation and principles of capillary electrophoretic separation and to
      review the recent research demonstrating the applicability of this technology to
      the clinical laboratory.

PMID- 7720238
TI  - Four agglutination assays evaluated for measurement of von Willebrand factor
      (ristocetin cofactor activity)
AB  - The concentration of von Willebrand factor (vWf) in patients' plasma can be
      determined by measuring the ristocetin cofactor activity (vWf R:Co). However,
      this vWf R:Co assay is time consuming, which limits its routine use. Several
      commercial vWf R:Co tests, based on agglutination of lyophilized fixed platelets,
      are available. We evaluated the slide tests and aggregometer assays from Behring
      and Organon Teknika and compared them with the classic vWf R:Co aggregometer
      method. The within-run and between-run precisions of the two slide tests were
      better than those of the aggregometer methods. The correlation studies between
      the four commercial assays and the classic aggregation method were based on 23
      plasma samples (range: 15-450% vWf R:Co). The correlation coefficients, which
      ranged from 0.923 to 0.950, did not differ significantly (P > 0.1). All four
      commercial assays gave significantly lower vWf R:Co values than the classic
      aggregation method (P < 0.01). We conclude that commercially available fixed
      platelets can be used for the rapid measurement of vWf R:Co with a slide test.
      The use of the aggregometer is time consuming and may result in a lower
      precision.

PMID- 7720239
TI  - Significance of low serum alkaline phosphatase activity in a predominantly adult
      male population.
AB  - The causes for low serum alkaline phosphatase (ALP) activity (reference range 30
      115 U/L) in a large Veterans Medical Center were reviewed. Of 69,864 ALP
      determinations made over a 4-year period, 130 were low (< 30 U/L, 0.19%),
      representing 88 individual patients. Of these, 83 (primarily men, 96%) patients'
      charts were reviewed and classified into two groups, those with and those without
      conditions previously reported to be associated with decreased serum ALP
      activity: 47% had conditions associated with low ALP activity, the most frequent
      being cardiac surgery and cardiopulmonary bypass (26.5%), malnutrition (12.0%),
      magnesium deficiency (4.8%), hypothyroidism (2.4%), and severe anemia (1.2%); 53%
      of patients did not have clinical conditions previously associated with low ALP
      activity. No case of clinically apparent hypophosphatasia, for which low ALP
      activity is the defining characteristic, was found in this population of
      veterans. A low serum ALP may be of significance in other patient populations
      such as children, where it is associated with achondroplasia and cretinism, or in
      postmenopausal women with osteoporosis taking estrogen replacement therapy. In
      the predominantly adult male population in this study, low ALP activity was rare;
      it was seen most frequently in cardiac surgery patients postoperatively, a
      clinical condition heretofore not commonly associated with low serum ALP
      activity.

PMID- 7720240
TI  - Automated measurement of alpha-amylase isoenzymes with 6(3)-deoxymaltotriose as
      selective amylase inhibitor.
AB  - We developed an automated method for measurement of alpha-amylase isoenzymes in
      serum by a single kinetic assay (SKA) and a double kinetic assay (DKA) with 2
      chloro-4-nitrophenyl-6(5)-azido-6(5)-deoxy-beta-maltopentaoside as a substrate
      and 6(3)-deoxymaltotriose (DOG3) as a novel selective amylase inhibitor. DOG3
      showed a large difference in inhibitory activity between human pancreatic alpha
      amylase (HPA; 86.9% inhibition) and salivary alpha-amylase (32.1% inhibition) at
      0.33 mmol/L. Constant inhibition was obtained immediately after addition of DOG3.
      The inhibitory effect did not change with variation in concentrations of amylase
      up to approximately 3000 U/L. The results obtained by SKA correlated well with
      those obtained by three methods: monoclonal antibody (r = 0.988), wheat germ
      inhibitor (r = 0.989), and DKA (r = 0.995). The within-run and between-run CVs
      for HPA were 0.63-2.32% on SKA, 0.69-1.81% on DKA. No significant interferences
      by endogenous serum compounds were observed with the proposed methods.

PMID- 7720241
TI  - Two alpha-chain hemoglobin variants, Hb Broussais and Hb Cemenelum, characterized
      by cation-exchange HPLC, isoelectric focusing, and peptide sequencing.
AB  - We here report the characteristics of two rare alpha-chain hemoglobin (Hb)
      variants. The variants were found during quantification of HbA1c by cation
      exchange HPLC with the Diamat glycohemoglobin analyzer. They were further
      characterized by isoelectric focusing and PolyCAT A cation-exchange
      chromatography. The structure of the abnormal Hbs was established by amino acid
      analysis after separation of the globin chains by reversed-phase chromatography,
      digestion with trypsin, separation of the peptides by reversed-phase
      chromatography, and amino acid sequencing. These studies showed that the two
      variants were Hb Broussais [alpha 90 (FG2)Lys-->Asn] and Hb Cemenelum [alpha 92
      (FG4)Arg-->Trp].

PMID- 7720242
TI  - Enzyme immunoassay of immunoreactive progastrin-releasing peptide(31-98) as tumor
      marker for small-cell lung carcinoma: development and evaluation.
AB  - Previously, using recombinant human progastrin-releasing peptide (ProGRP)(31-98),
      we developed a RIA for ProGRP(31-98) and demonstrated that the determination of
      serum ProGRP(31-98) was a reliable marker for small-cell lung carcinoma (SCLC)
      (Miyake et al., Cancer Res 1994;54:2136-40). Aiming for a more convenient assay
      system, we have now developed and evaluated a highly sensitive and specific ELISA
      for ProGRP(31-98). Only 50 microL of nonextracted serum is needed, and results
      are obtained in only 2 h. Intraassay and between-day CVs were 1.7-4.6% and 4.2
      6.8%, respectively. The log-log calibration curve was linear to 1000 ng/L, and
      analytical recovery was 91.5-108.7%. The detection limit of this assay, 1.9 ng/L,
      means that basal concentrations of ProGRP(31-98) were detectable in all healthy
      subjects. The cutoff value, based on the mean + 3 SD of concentrations in 247
      healthy subjects, was set to 45.1 ng/L. Serum concentrations exceeded this value
      in 18 of 25 SCLC patients, similar to the frequency of increased values found by
      RIA previously. In contrast, the frequency of increased serum ProGRP(31-98) in
      patients with nonmalignant pulmonary diseases or non-SCLC was quite low: 0% and
      5.0%, respectively. Such results may justify a clinical trial for evaluating this
      ELISA for the diagnosis and monitoring of SCLC patients.

PMID- 7720243
TI  - Age-related reference values for urinary excretion of sialic acid and deoxysialic
      acid: application to diagnosis of storage disorders of free sialic acid.
AB  - We have established by HPLC age-related reference intervals for sialic acid
      urinary excretion in 364 control individuals to assist in evaluating the clinical
      significance of the free sialic acid concentration in urine. In addition, an HPLC
      method for quantitative analysis of free deoxysialic acid was developed, and age
      related reference intervals for excretion of this compound in urine were
      established. In patients with storage disorders of free sialic acid (n = 11) the
      sialic acid excretion was increased 2- to 35-fold, compared with the mean value
      of the control subjects in the corresponding age group, and exceeded the interval
      in each case. The excretion of deoxysialic acid was within the reference interval
      in all of the patients, indicating that its metabolism was not affected in the
      disorders. The age-related reference values assist in evaluating the excretion of
      free sialic acid in the diagnosis of storage disorders of free sialic acid,
      especially in young children.

PMID- 7720244
TI  - Smith-Lemli-Opitz syndrome diagnosed by using time-of-flight secondary-ion mass
      spectrometry.
AB  - We describe a rapid and sensitive method involving time-of-flight secondary-ion
      mass spectrometry (TOF-SIMS) for specific laboratory diagnosis of the Smith-Lemli
      Opitz syndrome, which is characterized by massive (approximately 1000-fold)
      accumulation of the biosynthetic cholesterol precursor 7-dehydrocholesterol.
      Minute amounts of blood (1-50 microL) were extracted with n-hexane, and aliquots
      were analyzed by TOF-SIMS. 7-Dehydrocholesterol and its isomers were detected at
      491.3 mass units ([M + 107Ag]+) and cholesterol at 495.3 mass units ([M +
      109Ag]+). Quantitation of 7-dehydrocholesterol and cholesterol was achieved after
      saponification and addition of stigmasterol as internal standard. Whereas 7
      dehydrocholesterol and isomeric dehydrocholesterol were not detectable in
      controls, the patients revealed concentrations ranging between 0.84 and 1.25
      mmol/L. Comparison with results obtained by gas chromatography indicated that
      quantitation by TOF-SIMS yielded the sum of 7-dehydrocholesterol, isomeric
      dehydrocholesterol II, and sterol III, the latter two also being increased in the
      patients. Consistent with quantitation by gas chromatography, the cholesterol
      concentrations in the patients ranged between 1.54 and 2.12 mmol/L (controls:
      6.10 +/- 1.37 mmol/L).

PMID- 7720245
TI  - HLA class II genotyping: two assay systems compared.
AB  - In the last few years, a variety of DNA-based human leukocyte antigen (HLA)
      typing methods have emerged, revealing the extreme polymorphism of HLA genes.
      This polymorphism makes it difficult for a clinical laboratory to establish the
      best HLA typing strategy. In this study we have compared two techniques for
      performing HLA-DRB typing: a commercial rapid assay based on the polymerase chain
      reaction (PCR) followed by reverse dot-blot hybridization of the PCR products
      (the Inno-LiPA assay), and a method based on PCR followed by restriction fragment
      length polymorphism analysis. We found that both methods provide reliable results
      with a high rate of concordance (97%) and that Inno-LiPA is convenient for large
      scale routine typing. However, if a high-resolution allelic typing is required,
      each method lacks accuracy but using them in association improves the accuracy of
      the results.

PMID- 7720246
TI  - Electrochemical determination of low blood lead concentrations with a disposable
      carbon microarray electrode.
AB  - Lead concentrations in blood samples typical of unexposed individuals are
      determined by using square-wave anodic stripping voltammetry at a disposable 287
      element (15-35-microns diameter) carbon microarray electrode. Analysis of a
      series of low Pb-containing samples (blood [Pb] = 17 to 92 micrograms/L) by
      standard addition gives good accuracy (average bias vs graphite furnace atomic
      absorption spectroscopy = -4 micrograms/L) and precision (pooled SD = 7
      micrograms/L). The signal/noise ratio is improved by about an order of magnitude
      over that found at a single carbon disk (10 microns diameter), resulting in a
      detection limit (for the microarray) of 5 micrograms/L for a 60-s deposition of
      sample.

PMID- 7720247
TI  - 6 alpha-biotinylated estrone: novel tracer in competitive chemiluminescence
      immunoassay of estrone in serum.
AB  - We describe the development and validation of a labeled-hapten competitive
      immunoassay for determining total estrone in serum. For the hapten tracer we use
      the 6 alpha-biotinylated estrone derivative, 3-hydroxyestra-1,3,5(10)-trien-17
      one 6 alpha-N-(epsilon-biotinyl)aminocaproamide (Bio-E1). A specific polyclonal
      rabbit anti-estrone antibody is indirectly bound via an immobilized donkey anti
      rabbit antibody on microtiter plate wells. The amount of Bio-E1 bound is then
      measured with streptavidin-horseradish peroxidase conjugate, whereby the enzyme
      activity is quantified by an enhanced chemiluminometric method. For the assay,
      serum samples were extracted with solid-phase extraction cartridges. The assay
      dynamic range was 93-7400 pmol/L estrone, with a lower detection limit of 55
      pmol/L. An interassay imprecision (CV) of 12-14%, a recovery rate between 80% and
      110%, and a dilution linearity are demonstrated. Estrone serum concentrations
      were measured in healthy men and women and in women with polycystic ovary
      syndrome. Comparing the assay with a nonextraction RIA, we found an acceptable
      correlation for samples from 143 subjects of either sex. This enzyme immunoassay
      with biotin as the primary label and enhanced chemiluminescence signaling
      detection performs well for determining total estrone in serum and is readily
      adaptable to assays for other steroid hormones.

PMID- 7720249
TI  - Behavior of frozen serum pools and lyophilized sera in an external quality
      assessment scheme.
AB  - To further improve analytical accuracy in clinical chemistry, proficiency testing
      needs amelioration in the quality of materials tested and in target value
      assignment. To obtain information on the actual state-of-the-art in the Lombardy
      region of Italy, and to examine the behavior of different types of control
      materials (fresh-frozen human sera and lyophilized materials), we developed the
      following experimental design. Two human serum pools and two lyophilized sera
      were distributed to 32 laboratories for determination of glucose, creatinine,
      cholesterol, sodium, potassium, and gamma-glutamyltransferase (gamma-GT). Each
      analyte was measured in triplicate on each of 3 days. Target values for the
      controls were obtained with Reference Methods. The results show a good
      intralaboratory precision for every component but some accuracy problems for
      glucose, creatinine, cholesterol, and gamma-GT. Lyophilized materials showed some
      commutability problems for glucose, electrolytes, and gamma-GT, mainly with dry
      chemistry technology.

PMID- 7720248
TI  - Determination of pyridinoline and deoxypyridinoline in urine, with special
      attention to retaining their stability.
AB  - Urinary excretion of the pyridinium crosslinks pyridinoline (Pyr) and
      deoxypyridinoline (Dpyr) is used as a biochemical marker of bone resorption. The
      present study was undertaken to determine the long-term stability of these
      compounds in stored urine, using the HPLC method. Systematic investigation of
      their chemical stability in urine demonstrated that both the free and conjugated
      forms of Pyr and Dpyr are extremely stable: No significant changes were observed
      after 6 weeks at -20 degrees C storage (e.g., free Pyr 9.6 +/- 1.2 mumol/mol
      creatinine (before) and 10.6 +/- 3.2 (after); free Dpyr 2.3 +/- 0.2 mumol/mol
      creatinine (before) and 2.5 +/- 1.2 (after)). These results predict stability of
      urines stored for 10-20 years at -20 degrees C in the dark. Also, freezing and
      thawing as many as 10 times had no effect on the concentrations of the
      crosslinks. Study of the stability of the excretion pattern in healthy women
      showed substantially higher variations in excretions of free and total Dpyr (18%
      and 13%, respectively) than of Pyr (10% for both forms).

PMID- 7720250
TI  - Automated measurement of urinary iodine with use of ultraviolet irradiation.
AB  - We have modified an automated measurement system of urinary iodine (UI) and
      established a sensitive UI assay system by using ultraviolet (UV) digestion. The
      automated system is sensitive enough to detect concentrations of UI < 0.78
      mumol/L (< 10 micrograms/dL) in a small volume of urine (500 microL). Sample
      throughput is > 30/h, including a water washing. The within-assay imprecision
      (CV) was < or = 10% in the UI range of 0.10-3.00 mumol/L; the between-assay CV
      was usually < or = 15% in the same range. Analytical recovery of iodine added to
      urine samples was consistently > 90%. The theoretical values were recovered when
      UV irradiation was used but not in its absence. High (supraphysiological) doses
      of thiocyanate or ascorbic acid, which are major interfering substances to the
      ceric-arsenious acid reaction, did not interfere with this system. The
      correlation between UI determined by this method and by the acid digestion method
      was linear (r = 0.994). For samples containing iodine at < 1.00 mumol/L, the
      correlation between values by both methods was still significant (r = 0.937). UI
      in an iodine-deficient area in Ukraine, measured by this system, ranged from 0.06
      to 1.83 mumol/L (median 0.44 mumol/L, n = 95), significantly lower than in Japan
      (range 0.23-50.70 mumol/L, median 4.70 mumol/L, n = 84) and consistent with mild
      iodine deficiency. This modified automated assay system, therefore, is useful and
      applicable for screening UI in inhabitants of iodine-deficient areas.

PMID- 7720251
TI  - Automated homogeneous liposome-based assay system for total complement activity.
AB  - We developed an automated homogeneous immunoassay, based on immune lysis of
      dinitrophenyl (DNP)-labeled liposomes, for measuring total complement activity.
      Liposome lysis caused by complement activity was detected spectrophotometrically
      from entrapped glucose-6-phosphate dehydrogenase activity. Complement activity in
      human sera was quantified by comparison with a calibration curve. For ease of
      application to fully automated routine clinical analyzers, we adopted a two
      reagent system, one reagent containing a homogeneous population of small DNP
      labeled liposomes and one containing antibody/substrate. This system required
      calibration only once a week. Within-run and between-run CVs were 0.4-1.3% (n =
      10) and 1.8-4.7% (n = 10), respectively. Serum results were linear upon dilution
      (with saline) over a twofold range. Bilirubin, hemoglobin, Intrafat, and serum
      proteins such as rheumatoid factor, M protein, IgG, and IgA did not affect the
      assay results. The results (y) correlated well with those from a hemolytic
      complement activity test (x): y = 1.05x - 1.14, r = 0.92, on 66 samples in the
      range < 10- > 50 kU/L. This method should therefore be of great use for the
      determination of complement activity.

PMID- 7720252
TI  - Electrochemical dehydrogenase-based homogeneous assays in whole blood.
AB  - An electrochemical method has been developed for determining NADH in whole blood
      for dehydrogenase-based assays by flow-injection analysis. NADH generated by
      dehydrogenase is oxidized by an electron-transfer coupling reagent, 2,6
      dichloroindophenol (DCIP). The reduced form of DCIP (DCIPH2) is measured
      amperometrically by flow-injection analysis. Endogenous interferents were
      inhibited by p-hydroxymercuribenzoate. Electrode fouling by proteins was not
      observed under assay conditions. The Emit theophylline enzyme immunoassay and the
      hexokinase glucose assay were used as models. For the glucose assay, the
      intraassay CVs were 15% at 0.31 g/L and 3.5% at 1.82 g/L. Recoveries of glucose
      from whole blood (compared with that for aqueous standards) were 109%, 97.9%, and
      101% at 0.050, 2.00, and 5.00 g/L glucose, respectively, and 104%, 101%, and 102%
      for theophylline at concentrations of 5.0 (low), 16.4 (medium), and 30.2 (high)
      mg/L, respectively, with corresponding precisions of 12%, 9.5%, and 8.8%. Both
      assays correlated well with results by reference methods. These studies
      demonstrate that this method can measure NADH in whole blood without prior
      separation and that it is potentially applicable to other dehydrogenase-based
      assays in whole blood.

PMID- 7720253
TI  - Simultaneous assessments of exocrine pancreatic function by cholesteryl
      [14C]octanoate breath test and measurement of plasma p-aminobenzoic acid.
AB  - Two noninvasive tests for assessing pancreatic exocrine function, the cholesteryl
      [14C]octanoate breath test and the HPLCN-benzoyl-tyrosyl-p-aminobenzoic acid/p
      aminosalicylic acid (NBT-PABA/PAS) test, were simultaneously performed in nine
      patients with pancreatic exocrine insufficiency due to chronic pancreatitis and
      in nine healthy volunteers. 14CO2 output in breath and plasma PABA concentration
      rose slowly in patients but increased rapidly in healthy subjects. The
      measurement time giving the best discrimination between both groups was 120 min
      for the cholesteryl-[14C]octanoate breath test and 90 min for the plasma PABA
      test. At these points, both single-sample tests had essentially identical
      diagnostic sensitivity. The diagnostic sensitivities of the two single-sample
      tests were equal to that of the cumulative 6-h urinary PABA recovery and the
      cumulative 6-h urinary PABA/PAS ratio. We conclude that, for both the cholesteryl
      [14C]octanoate breath test and the plasma PABA test, a single test sample is
      sufficient for rapid detection of impaired exocrine pancreatic function.

PMID- 7720254
TI  - Elimination of paraprotein interference in determination of plasma inorganic
      phosphate by ammonium molybdate method.
AB  - Phosphate concentrations were determined in 52 cases of paraproteinemia. The
      unmodified acidic ammonium molybdate method produced 19% spuriously high results.
      The false increase of phosphate concentration was attributable to formation of
      precipitate in the reaction mixture. The precipitate was formed by interaction
      between immunoglobulins and the unmodified acidic ammonium molybdate reagent. The
      magnitude of interference bore no relation to the type, concentrations, or
      isoelectric point of the paraproteins or to the presence or absence of free light
      chains. Diluting the sample to approximately 40 g/L total protein reduced but did
      not always eliminate the interference. In some cases paraprotein concentration as
      low as 8 g/L falsely increased plasma phosphate results. Apparently, only IgG and
      IgM but not IgA paraproteins produced the interference. Deproteination by
      ultrafiltration or by treatment with trichloroacetic acid removed the
      interference. The Kodak slide method and the new modified Boehringer Mannheim
      phosphate test were found to be interference-free. However, in some cases the
      latter new formulation is sensitive to substantial changes in ionic concentration
      of the reaction mixture.

PMID- 7720255
TI  - Los Angeles County-University of Southern California Medical Center clinical
      pathology case conference: extreme hypermagnesemia in a neonate.
AB  - A preterm male infant born at 33 weeks of gestation developed respiratory
      depression and apnea at approximately 20 h after birth. Laboratory tests
      indicated severe hypermagnesemia, acidosis, and hypercalcemia. Cord blood and
      maternal blood concentrations of magnesium were normal. The effects and possible
      causes of hypermagnesemia are reviewed. The infant recovered with treatment,
      although the etiology of his hypermagnesemia remains unknown.

PMID- 7720256
TI  - Pseudo-pseudohypertriglyceridemia: a case of increased free glycerol without
      evidence for glycerol kinase deficiency.
AB  - High concentrations of glycerol in plasma may result in overestimation of
      triglycerides in chemical and enzymatic assays. Known causes of increased
      glycerol concentrations in blood include glycerol-contaminated blood-collector
      tubes and pseudohypertriglyceridemia, a condition caused by genetic defects in
      the gene for glycerol kinase. We report a patient with sudden hearing loss who
      presented with an increased blood glycerol concentration after undergoing an oral
      glycerol test.

PMID- 7720257
TI  - Digoxin immunoassay that avoids cross-reactivity from Chinese medicines.

PMID- 7720258
TI  - Automation of polymerase chain reaction tests to achieve acceptable contamination
      rates.

PMID- 7720259
TI  - Preventing actin interference in immunonephelometric measurements of vitamin D
      binding protein (Gc-globulin).

PMID- 7720260
TI  - Aluminum in serum determined by HPLC.

PMID- 7720261
TI  - PCR detection of the Taq1 restriction fragment length polymorphism linked to the
      ataxia telangiectasia locus.

PMID- 7720262
TI  - Abraham Flexner's legacy: a magnificent beneficence to American medical education
      and clinical chemistry.

PMID- 7720263
TI  - Falsely high serum free thyroxine concentration measured with Amerlite-MAB FT4.

PMID- 7720264
TI  - Reference interval for serum secretory IgA.

PMID- 7720265
TI  - Special issue: Education in clinical chemistry.

PMID- 7720266
TI  - Clinical chemistry as scientific discipline: historical perspectives.
AB  - The fundamental ideas which underlie clinical chemistry as an independent
      scientific field were formed over the course of centuries. Exactly 200 years ago
      the first modern concepts for this discipline were formulated in close connection
      with the restructuring of medical education during the French Revolution on the
      one hand, and the emergence of a new idea of a 'clinic' on the other hand.
      However, not until 1840 was clinical chemistry institutionalized as academic
      subject and simultaneously integrated into medical teaching. After about 1860,
      clinical chemistry was practiced by the clinicians themselves in close
      relationship with clinical activities, yet again with emphasis on teaching. In
      this period, clinics and hospitals established 'clinical laboratories'. With the
      start of the 20th century, after biochemistry had developed into an independent
      scientific field, clinical chemistry continued to evolve in close relationship
      with that latter discipline. This was particularly true in the United States,
      where an 'American School of Clinical Biochemistry' emerged which was to greatly
      influence the field.

PMID- 7720267
TI  - Education in clinical chemistry in Germany.

PMID- 7720268
TI  - Training and continuous education of clinical laboratory technologists and
      technicians.
AB  - The profession of clinical laboratory technologist has undergone profound changes
      in the last decades and scientific as well as technological advancement will
      cause further continued evolution. Therefore, adaptability to a rapidly evolving
      environment and willingness to continuously update knowledge as well as skills
      seem to be the most important demands confronting technologists. I compare the
      current training of clinical laboratory technologist in industrialized countries
      with emerging educational schemes, which include curricula based on national
      requirements comprising a total of 3-4 years of formal lectures and practical
      training.

PMID- 7720269
TI  - Education in clinical chemistry and laboratory sciences in Austria.

PMID- 7720271
TI  - Clinical biochemistry training in The Netherlands.
AB  - A unique situation for clinical biochemistry exists in the Netherlands, since it
      is nearly fully practised by science-oriented professionals. They are enlisted in
      the Register of Recognized Clinical Biochemists supervised by the Netherlands
      Society of Clinical Chemistry. Training as a clinical biochemist consists of a 4
      year period in a hospital laboratory; it is not a specific university education.
      Strictly specified requirements exist for trainee, tutor, laboratory and hospital
      to maintain the quality of our profession. The candidate has to become acquainted
      with the following aspects: general clinical biochemistry (including
      haematology), fundamental research, clinical orientation and management. Passing
      the yearly examination and publishing two articles in international journals are
      an obligation. Continuing education is not yet compulsory, but is well formalized
      within our society. European unification asks for one regulation of clinical
      biochemistry on a European level, both for professionals with a medical and a
      science-oriented background.

PMID- 7720270
TI  - Teaching clinical chemistry in central European countries--past and present.
AB  - Central Europe is traditionally referred to as the area occupied by the former
      Eastern Germany, Poland, Slovakia, Czech Republic and Hungary. In all of these
      countries great emphasis is placed on teaching clinical chemistry and biochemical
      pathology, both at undergraduate and postgraduate levels. In Czech Republic and
      in Poland analysis of blood, urine, body fluids, exudates and secretions as well
      as the fundamentals of interpretation of morbid states in biochemical terms are
      taught as an independent subject taking from 60 to 90 h of lectures, seminars and
      practical training. In Hungary, the fundamentals of clinical chemistry and
      biochemical pathology are included in courses of biochemistry, pathology and in
      clinical subjects, such as internal medicine and pediatrics. The postgraduate
      study of clinical biochemistry, which yields in all mid-European countries a
      certificate of specialisation in laboratory diagnostics (Poland), or clinical
      pathology (Czech Republic, Hungary), is based on at least 5 years experience in
      laboratory medicine and then extended studies including clinical biochemistry,
      haematology, cytology, microbiology, as well as the fundamentals of toxicology
      and immunology. A basic background in clinical practice is also required. In all
      countries in the area there also exists a well developed postgraduate education
      for laboratory workers without a medical background. These people can apply for a
      certificate in medical analytics (Poland), but they cannot work as clinical
      pathologists or laboratory diagnostic consultants.

PMID- 7720272
TI  - The impact of clinical biochemistry on university education in France.
AB  - In France, clinical biochemistry, similar to other disciplines of laboratory
      medicine, is taught in both the regular medical and pharmacy curricula, but
      medical teaching is oriented more towards the interpretation of laboratory
      findings than test performance. At present, there is no compulsory program of
      lifelong continuing education, but it is planned to introduce such an obligation
      in the near future. The practice of laboratory medicine is regulated strictly by
      the national Health Administration. Clinical laboratories are multidisciplinary,
      covering simultaneously clinical biochemistry, microbiology, parasitology,
      hematology and immunology. The only officially recognized laboratory profession
      is that of 'Director of a Laboratory for Medical Analysis'. The practice of this
      profession is only open to physicians and pharmacists, provided they graduated in
      'Medical Biology' after 4 years of specialized training through a particular type
      of residency called the 'internat'. The 'interns' are selected by competitive
      examination. After completing their curriculum, specialized physicians or
      pharmacists can without further examination or certification either enter a
      career in a hospital, a university, or both, or direct or co-direct a private
      laboratory. In this scheme, clinical biochemistry exists as a separate academic
      discipline, but barely as a distinct profession.

PMID- 7720273
TI  - Clinical biochemistry education in Spain.
AB  - Clinical biochemistry in Spain was first established in 1978 as an independent
      specialty. It is one of several clinical laboratory sciences specialties,
      together with haematology, microbiology, immunology and general laboratory
      (Clinical analysis, analisis clinicos). Graduates in Medicine, Pharmacy,
      Chemistry and Biological Sciences can enter post-graduate training in Clinical
      Chemistry after a nation-wide examination. Training in an accredited Clinical
      Chemistry department is 4 years. A national committee for medical and pharmacist
      specialties advises the government on the number of trainees, program and
      educational units accreditation criteria. Technical staff includes nurses and
      specifically trained technologists. Accreditation of laboratories is developed at
      different regional levels. The Spanish Society for Clinical Biochemistry and
      Molecular Pathology (SECQ), the national representative in the IFCC, has 1600
      members, currently publishes a scientific journal (Quimica Clinica) and a
      newsletter. It organizes a continuous education program, a quality control
      program and an annual Congress.

PMID- 7720274
TI  - Education in clinical chemistry in Japan.
AB  - In Japan, the education of clinical chemists has mainly depended on personal
      efforts of individuals in medical schools, pharmacy schools and independent
      laboratories for medical analysis. Through the Board of Clinical Pathologists,
      the Japanese Society of Clinical Pathology at present provides certification in
      clinical chemistry as a subspecialty to physicians and the Society also certifies
      medical technologists at two levels for several subspecialties, including
      clinical chemistry. At the same time, the Education Committee of the Japanese
      Society of Clinical Chemistry offers annual summer and winter seminars for
      continuing education. In the future, these programs will be integrated into a
      regular postgraduate continuing education structure. However, it is urgent for
      the Japanese Society of Clinical Chemistry to establish alternate qualification
      and certification programs for clinical chemists.

PMID- 7720275
TI  - Training of clinical laboratory professionals in Russia.
AB  - In Russia, specialized education of clinical laboratory physicians who work in
      the positions of medical technologists, head of laboratory or one of its
      divisions is conducted in various forms of postgraduate training, namely
      internship, primary specialization courses, advanced study courses, graduate
      clinical studies and postgraduate fellowship. Such education is offered at 14
      Departments for Clinical Laboratory Diagnostics, which are located within the
      Institutes for Advanced Medical Studies or at Faculties for Advanced Medical
      Studies in Medical Institutes. Until the present, the primary specialization
      courses and the advanced study courses have been the most prevalent forms of
      training clinical laboratory professionals. These two types of courses offer
      formal lectures, seminars as well as practical classes, and the course contents
      are regulated by a uniform curriculum promulgated by the Ministry of Health.
      Training in these courses is the necessary prerequisite to obtain degree of
      advanced qualification as an expert in clinical laboratory diagnostics, which in
      turn provides access to better remunerated positions.

PMID- 7720276
TI  - The impact of clinical biochemistry on the pre-doctoral medical curriculum: an
      Italian viewpoint.
AB  - Clinical biochemistry can be viewed as a subdiscipline of laboratory medicine,
      but is not confined to the practical aspects of laboratory testing as clinical
      chemistry is. Since medical studies comprise both theoretical education and
      practical training, clinical (bio)chemistry must be taught by preceptors
      experienced in clinical laboratory operations. In Italy, where medical education
      traditionally has been separated into basic sciences and clinical sciences,
      clinical biochemistry has been added as a course to bridge between the two phases
      of the curriculum. However, the broader changes in Italian medical training will
      create a more cohesive pattern of teaching, and the integration of different
      material into a 'layer cake' curriculum. In such a structure, clinical
      (bio)chemistry will be considered a clinical discipline devoted mainly to
      teaching the use of laboratory tests, while the linkage between basic and
      clinical sciences falls to general pathology and pathophysiology. Nevertheless,
      to avoid overlap and lack of propaedeutical coordination, the content of the
      clinical (bio)chemistry-course must be coordinated with both the basic and the
      clinical sciences. This viewpoint is also supported by IFCC/IUPAC guidelines on
      teaching clinical chemistry to medical students.

PMID- 7720277
TI  - Post-doctoral training of the non-physician doctoral scientist.
AB  - Postgraduate training of the non-MD clinical chemist (clinical biochemist) is for
      the most part 'on the job training'. There are few formally structured programs
      to achieve the necessary skills and understanding needed by individuals before he
      or she can assume the directorship of a modern clinical laboratory. The
      experience and training must include management, laboratory performance, medical
      interface, research and education.

PMID- 7720278
TI  - Teaching and training of clinical biochemists: sub-specialization.
AB  - Clinical biochemistry, as one of the major 'classic' specialties within the broad
      field of laboratory medicine, continues to evolve under several different
      circumstances: (1) subspecialization within clinical biochemistry itself; (2)
      growth of new areas of biotechnology; (3) blurring of traditional 'boundaries'
      between disciplines in laboratory medicine. Post-graduate training in clinical
      biochemistry poses a challenge to universities charged with the responsibility
      for such professional education, particularly with the need to integrate and
      articulate training for both medical and non-medical graduates. Development of a
      career ladder is one response to this challenge.

PMID- 7720279
TI  - Continuing clinical chemistry education in the United States.
AB  - Governmental licensing agencies, professional certifying organizations, and
      healthcare institutions are establishing increasingly comprehensive requirements
      for formal continuing education in all branches of medicine, including clinical
      chemistry. Administrative procedures have been developed to accredit continuing
      education programs, and documentation of participation is frequently required for
      renewal of state licenses, reappointment to hospital staffs, and recertification
      by medical specialty boards. The rapid development of science and technology in
      clinical chemistry makes effective continuing education a mandatory objective
      both for the individual clinical chemist and for the profession.

PMID- 7720280
TI  - Clinical chemistry education in the United States.
AB  - Entrance into a clinical chemistry career in the US can be obtained through a
      variety of avenues, ranging from very formal to no formal training requirements.
      A frequent starting point is through a formal medical technology program at the
      baccalaureate level. Nonphysicians, interested in an advanced career, have also
      the option to choose their point of entrance through a formal graduate or
      postdoctoral program. The main source for obtaining a Master of Science or
      Doctoral degree with a major in the clinical laboratory sciences, is through
      Departments of Pathology. Physicians desiring to subspecialize in clinical
      chemistry can obtain some of the training through a residency program in
      Pathology. Clinical chemistry is an essential component of both the clinical
      pathology (CP) residency and the combined residencies in anatomic and clinical
      pathology (AP/CP). In addition, fellowships in clinical chemistry are available
      for graduates with doctorate degrees in the chemical and biological sciences as
      well as for physicians with laboratory experience.

PMID- 7720281
TI  - Education in clinical biochemistry: the Canadian scene.
AB  - The Canadian Health Care System is operated governmentally at the provincial
      level although the costs and benefits are similar in every province. Most
      physicians are remunerated on the 'charge per service' basis, but laboratory
      physicians (including medical biochemists) are among the few who are remunerated
      by salary. The training of medical biochemists is regulated by the Royal College
      of Physicians and Surgeons of Canada by means of a residency program of 4 years
      duration, following graduation from medical school and completion of the required
      internship. The training of clinical biochemists, whose functions overlap many of
      those attributable to medical biochemists, is regulated by the recently created
      Canadian Academy of Clinical Biochemistry through a certification process
      incorporating written and oral examinations approximately 1 year apart.
      Recognized and accredited training programs for clinical biochemists exist in
      several medical schools: these courses are of 2 (occasionally 3) years duration
      and entry to these programs requires a Ph.D. and, preferably, some post-graduate
      research experience. Details of both medical and clinical biochemistry training
      programs reveal a difference in emphasis and duration rather than in course
      content, with medical trainees required to spend at least 1 of their 4 training
      years in clinical disciplines relevant to the practise of biochemistry.

PMID- 7720282
TI  - Training and education in clinical biochemistry in the United Kingdom.
AB  - In the United Kingdom, clinical biochemistry is practised by medical and non
      medical graduates. Their training is postgraduate, led by the profession and has
      a strong vocational orientation. Although there is considerable overlap between
      the training of medical and non-medical graduates, each group has a different
      career structure and different training requirements. The training of non-medical
      biochemists has recently been restructured. Their new training programme is
      described in detail; for comparison, the training of medical graduates is
      outlined.

PMID- 7720283
TI  - Education and clinical biochemistry in Australia.
AB  - Education of clinical biochemists within Australia occurs primarily after the
      individual has attained a primary degree (Science or Applied Science) and is
      employed within a clinical laboratory, public or private. In the case of medical
      graduates, professional education is conducted under the auspices of the Royal
      College of Pathologists of Australia and results in the successful candidate
      obtaining the status of Fellow of that professional body. While scientists have a
      number of means of obtaining postgraduate qualifications in clinical biochemistry
      it is the Membership and Fellowship examinations of the Australian Association of
      Clinical Biochemists (AACB) which have greatest recognition within the
      profession. The majority of the continuing education of, and training programmes
      for, clinical biochemists are undertaken by the AACB. Currently, there are no
      formal registration requirements for laboratory scientists within Australia.

PMID- 7720284
TI  - Evaluation of new self-learning techniques for the generation of criteria for
      differentiation of wide-QRS tachycardia in supraventricular tachycardia and
      ventricular tachycardia.
AB  - This study presents a comparison of three different methods for differentiating
      between supraventricular and ventricular tachycardias with wide-QRS complex. One
      set of criteria, derived using classical statistical techniques, was compared
      with two new self-learning computer techniques: the artificial neural networks
      and the induction algorithm approach. By analyzing the results obtained in an
      independent test set, using these new techniques, the criteria defined by the
      classical method could be improved.

PMID- 7720285
TI  - Emergency intracardiac defibrillation for refractory ventricular fibrillation.
AB  - Hemodynamically unstable ventricular arrhythmias induced during
      electrophysiologic testing almost always respond to prompt application of direct
      current transthoracic shocks. In rare cases, however, ventricular fibrillation
      may be refractory to conventional treatment. Recently, a technique of
      intracardiac defibrillation has been successfully used to resuscitate patients
      with ventricular fibrillation refractory to transthoracic defibrillation. We
      describe two patients with a history of myocardial infarction and left
      ventricular dysfunction who were admitted with symptomatic episodes of
      ventricular tachycardia. Both had inducible sustained monomorphic ventricular
      tachycardia. During a repeat electrophysiologic study in Patient No. 1 on
      procainamide and at the initial study in Patient No. 2, right ventricular burst
      pacing to terminate ventricular tachycardia resulted in ventricular fibrillation
      refractory to resuscitation efforts, including transthoracic defibrillation with
      360 J. Emergency intracardiac defibrillation with 200 and 360 J, respectively,
      successfully converted both patients to sinus rhythm. Both patients were
      subsequently discharged from the hospital on amiodarone. These cases illustrate
      the life-saving capabilities of intracardiac defibrillation.

PMID- 7720286
TI  - Hydrochlorothiazide-induced pulmonary edema with severe acute myocardial
      dysfunction.
AB  - A 73-year-old woman presented with acute pulmonary edema and hypotension less
      than 1 h after taking hydrochlorothiazide 50 mg, a reaction which has been
      reported as a rare but classic adverse drug response. Though prior cases have
      supported a noncardiogenic pulmonary edema syndrome, hemodynamic monitoring in
      this patient demonstrated a refractory low cardiac output state for more than 24
      h. In the absence of other etiologies, this represents a new finding.

PMID- 7720287
TI  - Portrait of a contributor: Wilhelm Ebstein (1836-1912).

PMID- 7720288
TI  - Electrocardiographic and segmental wall motion abnormalities in pancreatitis
      mimicking myocardial infarction.

PMID- 7720289
TI  - Atrial fibrillation, transesophageal echo, electrical cardioversion, and
      anticoagulation.

PMID- 7720290
TI  - Economics of lipid lowering with HMG CoA reductase inhibitors.

PMID- 7720291
TI  - Is ventricular wall stress rather than left ventricular hypertrophy an important
      contributory factor to sudden cardiac death?
AB  - Sudden cardiac death comprises a significant proportion of cardiac mortality in
      Western society. Left ventricular hypertrophy has been identified by many authors
      as a possible risk factor for sudden cardiac death, however, left ventricular
      hypertrophy develops in response to external stimuli on the heart as a means of
      normalizing wall stress. It is possible that the fundamental abnormalities in
      wall stress, rather than the left ventricular hypertrophy itself, pose the
      increased risk of sudden death. Left ventricular hypertrophy, the consequence of
      raised wall stress, is easy to measure and easy to study and it is understandable
      why this parameter should have received more attention. Wall stress by contrast
      is difficult to measure, and worse, is variable throughout the ventricle so that
      it cannot be measured in a single quantifiable figure. As a consequence, only a
      limited amount of attention has been paid to wall stress as a possible trigger
      mechanism for cardiac arrhythmia. However, there is evidence from both basic and
      clinical research to suggest that raised wall stress may be a risk factor for
      sudden cardiac death and cardiac arrhythmia. This review discusses the evidence
      for and against left ventricular hypertrophy and wall stress as risk factors for
      sudden cardiac death, and also presents recent evidence that left ventricular
      hypertrophy in isolation can protect the heart against the arrhythmogenic effects
      of raised wall stress.

PMID- 7720292
TI  - Cardiac complications of cocaine abuse.
AB  - Cardiac complications of cocaine abuse and a rational approach to evaluating and
      managing them are described. Cardiac abnormalities reported among asymptomatic
      cocaine abusers include echocardiographic left ventricular hypertrophy and
      segmental wall motion abnormalities. Electrocardiogram may reveal increased QRS
      voltage, ST-T changes, and pathologic Q waves. Episodes of ST elevation may be
      seen during Holter monitoring. The management of cocaine-abusing patients who
      present to an emergency room with acute chest pain is controversial because the
      two reported studies yielded conflicting results regarding the incidence of
      myocardial infarction (MI). Even in the absence of infarction,
      electrocardiographic abnormalities are common among these patients, which
      complicates the decision-making regarding hospitalization. Pathophysiology of
      cocaine-related MI is discussed. Distinct clinical features of cocaine-related MI
      make it clear that the association between the two is not just temporal. However,
      considering the number of persons abusing cocaine, it is a rarity. Beta
      adrenergic blockers should be avoided in the treatment of cocaine-induced
      myocardial ischemia which is best treated with nitrates and calcium-channel
      blockers. Reports of cocaine-induced myocarditis and cardiomyopathy are reviewed.
      Experimental studies and clinical case reports suggest that cocaine may cause
      lethal arrhythmias. Cocaine prolongs repolarization by a depressant effect on
      potassium current and may generate early afterdepolarizations. It is possible
      that cocaine-associated arrhythmias are secondary to vasospasm-related ischemia
      and reperfusion as well.

PMID- 7720293
TI  - Evaluation of QRST isointegral maps in detecting posterior myocardial infarction
      with and without conduction disturbance.
AB  - We investigated the usefulness of QRST isointegral maps (I-maps) for detecting
      posterior myocardial infarction (MI) with and without conduction disturbance. The
      I-maps were recorded during sinus rhythm and right ventricular (RV) pacing, which
      simulated left bundle-branch block (LBBB) in 19 patients with and in 20 patients
      without MI. Data on 608 normal subjects were used as controls. The "-2 SD area,"
      where the QRST integral value was less than the lower limit of the normal range,
      was assessed by sigma DM (sum of QRST integral values below the normal range).
      Posterior MI was diagnosed with a sensitivity of 84%, a specificity of 90%, and a
      diagnostic accuracy of 87%, assuming that MI was present if sigma DM exceeded 50
      mVms. During simulated LBBB, when the criterion sigma DM more than 250 mVms was
      used, the sensitivity, specificity, and diagnostic accuracy were 79, 75, and 77%,
      respectively. Thus, I-maps may be useful in detecting posterior MI in patients
      with and without an intraventricular conduction disturbance.

PMID- 7720294
TI  - Complications of warfarin therapy monitored by the International Normalized Ratio
      versus the prothrombin time ratio.
AB  - The objective of our study was to determine the rates of bleeding complications
      and thromboembolic events in patients receiving oral anticoagulant therapy
      monitored with the prothrombin time (PT) ratio versus therapy monitored with the
      International Normalized Ratio (INR) using a retrospective time-series study
      design. Over 650 patients enrolled in a large anticoagulation clinic were studied
      during two time periods corresponding to the use of the PT ratio versus the INR
      to guide anticoagulant therapy, with over 400 patient-years of follow-up for each
      time period. The rate of bleeding complications using the PT ratio to guide
      therapy was 6.7% (1.2% major, 5.5% minor) per patient-year, compared with 2.9%
      (0% major, 2.9% minor) using the INR (p = 0.02). The rate of thromboembolic
      complications was 1.0% using the PT ratio, compared with 0.2% using the INR (p =
      NS). Therapy monitored with the INR required 19.8 visits per year, compared with
      20.7 visits per year using the PT ratio. We conclude that the INR should be used
      to monitor oral anticoagulant therapy in an effort to reduce bleeding
      complications while maintaining an acceptable rate of thromboembolic events.

PMID- 7720295
TI  - Importance of the time of onset of supraventricular tachyarrhythmias on prognosis
      of patients with acute myocardial infarction.
AB  - It is known that left ventricular (LV) function, severity of coronary artery
      disease, and the presence of ventricular arrhythmias are major determinants of
      prognosis in patients surviving an acute myocardial infarction (AMI). However,
      little is known about the relationship between the time of onset of
      supraventricular tachyarrhythmias (SVTs) and mortality. Therefore, this study was
      carried out in a 48-months period on 131 patients with AMI who presented with SVT
      during hospitalization. Of these, 53 patients (40.5%) had arrhythmia within < 12
      h of MI, while 78 patients (59.5%) had arrhythmia between 12 h and 4 days. The
      arrhythmias studied were atrial fibrillation, atrial flutter, and paroxysmal
      supraventricular tachycardia. The patients were similar for age, gender, coronary
      risk factors, creatine kinase-MB peak, cardioversion and LV function.
      Angiographic features for patients with the < 12-h onset of arrhythmia were:
      86.7% of the patients had uniarterial lesions, 8.9% had biarterial lesions, and
      4.4% had triarterial lesions. Patients with the 12-h-4-day onset had 16.1%,
      53.2%, and 30.6% (p < or = 0.05) of the respective lesions. Inferior wall
      myocardial infarction was more frequent among patients with the earlier onset
      (60.4%), while patients with the later onset presented more anterior wall
      infarctions (50.0%). Only 11.3% of the patients with the earlier onset presented
      with severe in-hospital congestive heart failure (Killip classes III-IV), versus
      62.8% of the patients with the later onset (p < or = 0.0001).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7720296
TI  - The effects of intracoronary adenosine on preconditioning during coronary
      angioplasty.
AB  - There is evidence that the first balloon inflation during coronary angioplasty
      provides a preconditioning stimulus leading to decreased ischemia during
      subsequent balloon inflations. Endogenous adenosine release may play a role in
      ischemic preconditioning. Therefore, intracoronary adenosine administration prior
      to the first balloon inflation during percutaneous transluminal coronary
      angioplasty (PTCA) might modify the preconditioning response to the first balloon
      inflation. Forty-one patients underwent double-blind randomization to treatment
      with 100 mcg of intracoronary adenosine or placebo prior to coronary angioplasty.
      Twenty patients (11 adenosine, 9 placebo) had complete resolution of ischemia
      between inflations allowing comparison between the first and second inflation. An
      angioplasty guidewire was used to obtain an intracoronary electrocardiogram. The
      mean reduction in ST elevation during the second inflation compared with the
      first was 4.8 mm in the placebo group and -0.8 in the adenosine group (p < 0.05
      placebo vs. adenosine). Seven of 9 placebo patients had a decrease in ischemia
      during the second inflation compared with the first, while only 2 of 11 adenosine
      patients showed a reduction. It was concluded that (1) the first inflation during
      PTCA is a preconditioning stimulus leading to a decrease in ischemia during later
      inflations, and (2) intracoronary adenosine administration prior to PTCA modifies
      the preconditioning effect of the first inflation. These data suggest that
      adenosine plays a role in ischemic preconditioning in humans.

PMID- 7720297
TI  - Pathology of tricuspid valve stenosis and pure tricuspid regurgitation--Part I.
AB  - This three-part article examines the histologic and morphologic basis for
      stenotic and purely regurgitant tricuspid valves. In Part I, conditions producing
      tricuspid valve stenosis are reviewed. In over 90% of stenotic tricuspid valves,
      the etiology is rheumatic disease. In isolated tricuspid stenosis, the etiology
      is either carcinoid or congenital. Rare causes of tricuspid stenosis include
      active infective endocarditis, metabolic or enzymatic abnormalities (Fabry's,
      Whipple's disease), and giant blood cysts.

PMID- 7720298
TI  - Prominent small bowel Ga-67 uptake associated with Yersinial and tuberculous
      enterocolitis.
AB  - The nuclear medicine evaluation of the immunocompromised patient with fever of
      unknown origin may include the use of either labeled leukocytes or Ga-67 citrate,
      or both, in the search for an infectious focus. In recent years, labeled
      leukocytes (In-111 or Tc-99m) seem to have been employed preferentially by some.
      This is especially the case when the abdomen is a suspected site of involvement
      because of the normal colonic excretion of gallium that may complicate the
      interpretation of this study. The authors present the case of an
      immunocompromised patient with the interesting scintigraphic pattern of diffuse
      large and small bowel uptake of gallium secondary to biopsy proven Yersinia and
      tuberculous enterocolitis. A review of the recent literature reveals only one
      other similar case in which Yersinial disease was detected by Ga-67 scintigraphy.
      The present case illustrates that gallium's avidity for the atypical, less
      pyogenic, opportunistic infections common in immunocompromised patients justifies
      its continued use in such settings and, specifically, whenever tuberculosis is
      suspected.

PMID- 7720299
TI  - Visualization of a perforated small bowel duplication during Meckel's
      scintigraphy.
AB  - A case of a small bowel tubular duplication is described. It was lined with
      ectopic gastric mucosa which showed a perforation. The diagnosis was made
      preoperatively by Tc-99m pertechnetate scintigraphy.

PMID- 7720300
TI  - Diagnosis of Menetrier's disease with Tc-99m human serum albumin scintigraphy.
AB  - Technetium-99m labeled human serum albumin has been shown to detect protein
      leakage into the bowel. A case of a young adult is presented with endoscopic and
      pathological correlation of scintigraphic findings supporting Menetrier's
      disease.

PMID- 7720301
TI  - Estimation of radiation absorbed doses to the red marrow in radioimmunotherapy.
AB  - Myelotoxicity is the dose-limiting factor in radioimmunotherapy. Traditional
      methods most commonly used to estimate the radiation adsorbed dose to the bone
      marrow of patients consider contributions from radionuclide in the blood and/or
      total body. Targeted therapies, such as radioimmunotherapy, add a third potential
      source for radiation to the bone marrow because the radiolabeled targeting
      molecules can accumulate specifically on malignant target cells infiltrating the
      bone marrow. A non-invasive method for estimating the radiation absorbed dose to
      the red marrow of patients who have received radiolabeled monoclonal antibodies
      (MoAb) has been developed and explored. The method depends on determining the
      cumulated activity in three contributing sources: 1) marrow; 2) blood; and 3)
      total body. The novel aspect of this method for estimating marrow radiation dose
      is derivation of the radiation dose for the entire red marrow from radiation dose
      estimates obtained by detection of cumulated activity in three lumbar vertebrae
      using a gamma camera. Contributions to the marrow radiation dose from marrow,
      blood, and total body cumulated activity were determined for patients who
      received an I-131 labeled MoAb, Lym-1, that reacts with malignant B-lymphocytes
      of chronic lymphocytic leukemia and nonHodgkin's lymphoma. Six patients were
      selected for illustrative purposes because their vertebrae were readily
      visualized on lumbar images. The radiation doses to the marrow contributed by
      nonpenetrating emissions in the marrow blood and penetrating emissions in the
      total body were similar in these patients with a mean of 0.2 and 0.3 rads per
      administered mCi from the blood and total body, respectively.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7720302
TI  - Serial reduction of ventilation in lung with congenital absence of pulmonary
      artery.
AB  - A 3-year-old boy with unilateral absence of the right pulmonary artery had a lung
      scan that demonstrated 46% of total ventilation on that side. This had fallen to
      39% by 2 years later, and at 11 years after the first study the value was 30%.
      Ventilation lung imaging may be useful in demonstrating the degree of ventilatory
      dysfunction in a lung compromised by absence of the pulmonary artery. Possible
      causes of the pulmonary damage are discussed.

PMID- 7720303
TI  - Tc-99m MAA lung perfusion scintigraphy performed before and after pulmonary
      embolectomy for saddle-type pulmonary embolism.
AB  - A 58-year-old man had shortness of breath, hypotension, and decreased partial
      pressure of oxygen (PO2) on the eighteenth day after undergoing craniotomy for a
      meningioma. Tc-99m MAA pulmonary perfusion scintigraphy showed little perfusion
      to the right lung and left lower lung and multiple perfusion defects in the left
      upper lung. Although the results of concurrent chest radiography were negative
      for pulmonary infiltrates, pulmonary angiography demonstrated a saddle-type
      embolism. The patient underwent emergency pulmonary artery embolectomy to remove
      blood clots and organized thromboemboli from the main pulmonary artery and the
      right and left pulmonary arteries. The patient's postoperative course was
      uneventful, and a second Tc-99m MAA lung perfusion scan demonstrated marked
      improvement in lung perfusion.

PMID- 7720304
TI  - Scintigraphic study of propylthiouracil induced submassive hepatic necrosis.
AB  - Drug induced hepatitis is a rare complication of thiourea antithyroid drugs. In
      some patients, the hepatotoxicity may be severe and lead to submassive hepatic
      necrosis (SHN). Submassive hepatic necrosis is a potentially fatal complication
      which is usually recognized on the liver biopsy and histological examination or
      autopsy. In the case presented here, SHN was identified on Tc-99m SC liver
      images. Sharply defined intrahepatic photopenic abnormalities without significant
      colloid shift were noted. SPECT images were most remarkable and exhibited
      extensive liver necrosis. Resolution of hepatic abnormalities correlated with
      clinical and biochemical resolution of SHN. In patients with propylthiouracil
      hepatotoxicity, serial liver SPECT images with Tc-99m SC appear helpful for the
      diagnosis and follow up of SHN and, in an appropriate clinical context, may
      obviate the need for liver biopsy.

PMID- 7720305
TI  - Scintigraphic cerebral spinal fluid leak study in a child with recurrent
      meningitis after resection of a frontal meningocele.
AB  - An In-111 DTPA cerebrospinal fluid (CSF) leak study was performed on a 3-year-old
      boy admitted with recurrent meningitis. He was born with a congenital
      encephalocele that was surgically resected at 7 days-of-age. A residual skull
      floor defect with a recurrent tumor of the nasal radix was clinically suspected.
      Computed tomography and MRI scans could not confirm or rule out the presence of a
      CSF leak. The scintigraphic study clearly demonstrated a leak into the left
      naris. A large leptomeningeal cyst extending down into the left nares was
      resected and a defect in the left frontal calvarium, identified as the source of
      the CSF leak, was repaired at surgery.

PMID- 7720306
TI  - Differing scintigraphic patterns of lumboperitoneal shunt dysfunction in patients
      with normal pressure hydrocephalus and pseudotumor cerebri.
AB  - The scintigraphic patterns of dysfunctioning lumboperitoneal shunts (LPS) may
      vary with the underlying disease. The authors reviewed 22 LPS studies performed
      on 15 patients during the past 2 years and correlated the findings with the
      patency status of the shunt as determined by brain CT/MRI and surgical revision.
      Most of the patients also had cerebrospinal fluid (CSF) pressure monitoring.
      Fifteen studies were performed in patients with LPS for the treatment of normal
      pressure hydrocephalus (NPH) and 7 were performed in patients with LPS for
      pseudotumor cerebri (PTC). After intrathecal administration of 0.5-1 mCi of In
      111 DTPA, sequential 1 minute images of the abdomen were obtained for 20 minutes.
      Static images of the abdomen were then obtained at 30 minutes and 1, 2, 4, and 24
      hours with imaging of the head at 4 and 24 hours. All NPH patients with partial
      obstruction had tracer activity in the peritoneal cavity with little or no shunt
      tubing visualization. However, all had marked penetration of the tracer into the
      lateral ventricles. Pseudotumor cerebri patients with partial obstruction also
      showed tracer entry into the peritoneal cavity. Shunt tubing and tracer
      extravasation into the needle tract, at the site of lumbar puncture was seen only
      in patients of PTC, probably because of high intracranial pressure. Although the
      tracer flowed quickly into the basal cistern in all patients with PTC, it entered
      the lateral ventricles. Complete shunt obstruction was characterized by
      nonvisualization of activity in the peritoneal cavity and flow of the tracer into
      the basal cistern within 1 hour after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720307
TI  - I-123 MIBG scintigraphy in adults. A report of clinical experience.
AB  - Thirty-one adult patients with clinical findings suggestive of pheochromocytoma
      were studied with I-123 MIBG. All patients had images obtained at 24 and 48
      hours. Five patients had abnormal uptake proved to be because of I-123 MIBG avid
      tumors. The remaining 26 patients had no proven tumors and showed physiologic
      uptake in various organs. The 24-hour images were of high quality. In all cases,
      the 48-hour images contributed no significant additional information. Only in 1
      patient did the 48-hour image add some certainty. Physiologic uptake was seen in
      the salivary glands, liver, G.I. tract, and urinary bladder in all patients
      (100%). Uptake was also observed in the lung and heart (90%), normal adrenal
      glands (32%), thyroid (29%), spleen (23%) uterus (13%), and neck muscles (6%).
      The authors' experience indicates that I-123 MIBG gives superior images compared
      to the previously used I-131 MIBG, that the optimum imaging time for adults is 18
      24 hours, and that normal distribution patterns including uterine and neck muscle
      uptake should be familiar to physicians interpreting the studies.

PMID- 7720308
TI  - Utility of Tc-99m mebrofenin scintigraphy in the assessment of infantile
      jaundice.
AB  - Technetium-99m mebrofenin hepatobillary excretory patterns were assessed in 36
      infants with hyperbilirubinemia. Phenobarbital was administered to 22 patients
      before imaging. Final diagnoses included: intrahepatic cholestasis (14 patients),
      neonatal hepatitis (nine patients), biliary atresia (eight patients), alpha-1
      antitrypsin deficiency (two patients), Alagille's syndrome (two patients), and
      cystic fibrosis (one patient). No patient with biliary atresia showed bowel
      activity by 24 hours. Of the 28 infants without biliary atresia, 23 (82%) had
      bowel activity visualized by 6-8 hours and 26 (90%) had bowel activity by 24
      hours. Two had no bowel activity at 24 hours: one had cystic fibrosis and one had
      neonatal hepatitis. Of the 26 patients with bowel visualization, the time to
      visualize bowel did not differ between patient groups with and without
      phenobarbital induction. All of the patients with hepatitis, including those with
      marked dysfunction, showed good hepatic uptake. Mebrofenin scintigraphy is an
      important imaging technique in the diagnostic evaluation of infants with
      hyperbilrubinemia. In addition to biliary atresia, intrahepatic cholestasis due
      to cystic fibrosis and severe neonatal hepatitis may also cause bowel
      nonvisualization up to 24 hours. The results of this study suggest phenobarbital
      induction may not be needed when Tc-99m mebrofenin scintigraphy is used for the
      assessment of infantile jaundice.

PMID- 7720309
TI  - Diffuse Tl-201 uptake in the lungs. Etiologic classification and pattern
      recognition.
AB  - Diffuse Tl-201 uptake in the lungs could be because of cardiac, neoplastic,
      inflammatory, or interstitial lung disease. Examples from the different
      categories, differential diagnosis, and different patterns are presented. The
      authors discuss the different mechanisms of increased Tl-201 uptake in the lungs
      which vary according to the underlying pathology.

PMID- 7720310
TI  - Pulmonary microvascular cytology sampling confirms the lung scan finding of
      "contour mapping".

PMID- 7720311
TI  - Localization of mediastinal parathyroid adenoma in recurrent postoperative
      hyperparathyroidism with Tc-99m sestamibi SPECT.

PMID- 7720312
TI  - Asymmetrical localization of Tc-99m Sn F2 colloid labeled white cells in the bony
      pelvis after radiotherapy.

PMID- 7720313
TI  - Ga-67 scan findings in global splenic infarction and abscess.

PMID- 7720314
TI  - Saliva leakage from the parotid gland.

PMID- 7720315
TI  - Multiple coarctations of the pulmonary artery. A rare etiology of mismatched
      perfusion defects on radionuclide imaging.

PMID- 7720316
TI  - Left ventricular diverticulum. Image correlation.

PMID- 7720317
TI  - Scintigraphic evidence of post-surgical rib regrowth.

PMID- 7720318
TI  - Hepatobiliary scintigraphy in spontaneous perforation of the common bile duct.

PMID- 7720319
TI  - Tc-99m MDP scanning in a patient with extensive fibrodysplasia ossificans
      progressiva.

PMID- 7720320
TI  - The scintigraphic presentation of Pott's disease.

PMID- 7720321
TI  - Colonic localization of labeled leukocytes in critically ill patients.
      Scintigraphic detection of pseudomembranous colitis.
AB  - This study assesses the causes of colonic localization of labeled white blood
      cells (WBCs) in critically ill patients who had undergone leukocyte scintigraphy
      for suspected infection. Forty-two patients showed abdominal or pelvic WBC
      localization; 20 of these had a pattern of colonic localization, and some also
      showed a pattern of small bowel activity. Eight of the 20 patients had documented
      gastrointestinal bleeding. White blood cell scintigraphy in these eight patients
      showed a pattern of multifocal and/or regional bowel activity that changed in
      intensity and location from early (3-5-hour) to delayed (18-28-hour) images. In
      contrast, 5 of the 6 patients with documented pseudomembranous colitis (PMC)
      showed intense WBC localization involving most of the colon. In 3 of these 5
      patients, early and delayed images were acquired and showed a relatively constant
      pattern of WBC localization. The sixth PMC patient had been treated with
      vancomycin before leukocyte scintigraphy and showed minimal distal small bowel
      activity on early images and only mild regional colonic activity on delayed
      images. As in the patients with gastrointestinal bleeding, the remaining six
      patients showed either focal or regional activity of variable intensity that
      changed over time. In critically ill patients, gastrointestinal bleeding and PMC
      accounted for 14 of the 20 patients in which labeled leukocyte scintigraphy
      exhibited colonic activity. A pattern of diffuse, intense colonic radiotracer
      activity which persists from early to delayed imaging strongly suggests the
      presence of PMC in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720322
TI  - Microalbuminuria in an adolescent cohort with insulin-dependent diabetes
      mellitus.
AB  - To document the incidence of microalbuminuria in children and adolescents with
      longstanding insulin-dependent diabetes mellitus (IDDM) and to compare the
      clinical characteristics and determinant risk factors of those with and without
      microalbuminuria, 135 adolescent patients with IDDM for 5 years or longer were
      evaluated. The study population was divided on the basis of microalbumin
      excretion into normal (< 20 micrograms/min), incipient (20-200 micrograms/min),
      and overt (> 200 micrograms/min) nephropathy groups. There were 106 patients in
      the normal group, 24 patients in the incipient group, and five in the overt
      nephropathy group. Glycosylated hemoglobin, cholesterol concentration, and
      glomerular filtration rate (GFR) were analyzed. The incidence of incipient and
      overt nephropathy was 17.8% and 3.7%, respectively. Mean cholesterol
      concentration in the incipient and overt nephropathy groups (208 +/- 39 mg/dL
      [5.4 +/- 1.0 mmol/L]) and 227 +/- 49 mg/dL [5.9 +/- 1.3 mmol/L], respectively)
      was significantly higher than the normal group (186 +/- 37 mg/dL [4.8 +/- 0.9
      mmol/L] P < 0.05). Similarly, systolic and diastolic blood pressures were
      significantly higher in the incipient and overt nephropathy groups compared to
      the normal group. This study confirms the high incidence of incipient and overt
      nephropathy in adolescents with IDDM early in the course of the disease.

PMID- 7720323
TI  - Screening for psychosocial dysfunction in pediatric inpatients.
AB  - Screening pediatric inpatients for psychosocial dysfunction offers physicians an
      opportunity to identify emotional and behavioral problems that might otherwise go
      unrecognized. In this study, the Pediatric Symptom Checklist (PSC), a brief,
      parent-completed questionnaire, which has been validated in a variety of
      outpatient settings, was used to screen 98 pediatric inpatients. Results
      indicated that the PSC can be easily administered in a busy inpatient setting and
      is well-tolerated by both house staff and patients' parents as a routine part of
      the admissions process. The percentage of children who screened positive with the
      PSC in this inpatient setting was similar to the percentages generated by using
      the PSC in outpatient settings. Routine use of the PSC in inpatient settings
      serves to heighten house staff awareness of psychosocial concerns and facilitate
      parent-physician discussion of pediatric mental health issues.

PMID- 7720324
TI  - Lung abscess in infants and children.
AB  - We retrospectively reviewed 18 cases of primary lung abscess and 10 cases of
      secondary lung abscess in infants and children during a 6-year period. Among 18
      patients with primary abscesses, nine were boys and nine girls, from 9 months to
      20 years old, but only two of 18 were less than 5 years old. Each had a solitary
      abscess. Location of abscesses included the right lower lobe (8), the right upper
      lobe (3), the left upper lobe (1), and the left lower lobe (6). One patient had
      Streptococcus pneumoniae bacteremia. Other bacterial isolates were from the upper
      respiratory tract and of uncertain significance. All patients recovered, although
      lobectomy was considered necessary in five patients because of failure to respond
      to intravenous antibiotic therapy. Secondary lung abscesses occurred in six boys
      and four girls who were from 2 1/2 months to 13 years old. All 10 had solitary,
      right-sided lesions, seven in the right lower lobe and three in the right upper
      lobe. Bacteria of unclear significance were recovered from three of 10 patients,
      while two had documented gram-negative bacteremia. Three secondary abscess
      patients underwent lobectomy because of perceived inadequate response to medical
      therapy, including intravenous antibiotics. Based upon the literature and our
      experience, therapy for pulmonary abscess should include a parenteral antibiotic
      with gram-positive activity against both penicillinase-producing Staphylococcus
      aureus and anaerobes for a minimum of 3 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720325
TI  - An evaluation of parental concerns and misperceptions about heart murmurs.
AB  - This study sought to determine the extent of anxiety and misperceptions about
      heart murmurs for consenting parents of 182 children referred for first-time
      pediatric cardiology assessment (including echocardiography) of a heart murmur.
      From questionnaires completed before assessment, 22% of parents indicated that
      they were extremely concerned, and only 16% could define a heart murmur as a
      sound made by the heart. From 1-month follow-up questionnaires obtained from
      parents of children without heart disease at assessment, 10% continued to believe
      that their child had a heart problem. Cardiology assessment may not provide
      complete reassurance to all families and additional interventions may be
      necessary.

PMID- 7720326
TI  - Multicystic dysplasia of the kidney.

PMID- 7720327
TI  - Adolescents and AIDS prevention. The pediatrician's role.

PMID- 7720328
TI  - Preventing AIDS in teenagers in the 1990s.

PMID- 7720329
TI  - Treatment of Stevens-Johnson syndrome with pooled human intravenous immune
      globulin.

PMID- 7720330
TI  - Poisoning of a 21-month-old child by a baby-sitter.

PMID- 7720331
TI  - Immunizations. Toddler documentation gap.

PMID- 7720332
TI  - Agenesis of the trachea.

PMID- 7720333
TI  - Perceived anxiety of pediatric patients to magnetic resonance.

PMID- 7720334
TI  - Phototherapy for neonatal jaundice in infants with cephalhematomas.
AB  - The efficacy of phototherapy in a group of infants with nonhemolytic
      hyperbilirubinemia and no cephalhematomas was compared with a second group of
      infants with large cephalhematomas (> 7 cm across), but similar in all other
      aspects. The cephalhematoma group demonstrated significantly lower hemoglobin
      (Hb) and hematocrit (hct) values (P < .0001, P < .002 respectively) than the
      standard group, even after the latter group had been adjusted by stratification
      (P < .0001, P < .005) such that the starting bilirubin concentration, birth
      weight, and gestational age were highly comparable to the cephalhematoma group.
      The bilirubin concentrations of the cephalhematoma, original, and adjusted groups
      were 277.8 +/- 5.8 mumol/L (16.24 +/- 0.03 mg/dL), [mean +/- sem], 265.2 +/- 0.5
      mumol/L (15.50 +/- 0.03 mg/dL), and 275.2 +/- 0.9 mumol/L (16.09 +/- 0.05 mg/dL),
      respectively. The postnatal age at the start of phototherapy in the
      cephalhematoma group was comparable with that of the standard group before and
      after adjustment. Phototherapy was equally effective in the cephalhematoma and
      standard (original and adjusted) groups of infants, in terms of duration, 24-hr
      decline, and overall decline/hr for the duration of exposure. The proportionate
      24-hr decline was 24.02 +/- 1.90% vs 20.99 +/- 0.23% and 22.61 +/- 0.48% and
      overall decline/hr was 0.83 +/- 0.06% vs 0.74 +/- 0.01% and 0.78 +/- 0.01%. We
      conclude that the sequestrated blood in the cephalhematomas did not significantly
      interfere with the efficacy of phototherapy.

PMID- 7720335
TI  - Assessing cell proliferation: a methodological review.

PMID- 7720336
TI  - L-arginine increases exhaled nitric oxide in normal human subjects.
AB  - 1. Endogenous nitric oxide plays an important physiological role and is
      synthesized by several isoforms of nitric oxide synthase from the semiessential
      amino acid L-arginine. Nitric oxide is detectable in the exhaled air of normal
      individuals and may be used to monitor the formation of nitric oxide in the
      respiratory tract. 2. We have investigated the effect of orally administered L
      arginine (0.05, 0.1, 0.2 g/kg) compared with matched placebo on the concentration
      of nitric oxide in the exhaled air in 23 normal individuals. 3. L-Arginine caused
      significant increases in the concentration of nitric oxide in exhaled air at
      doses of 0.1 and 0.2 mg/kg, which was maximal 2 h after administration. This was
      associated with an increase in the concentration of L-arginine and nitrate in
      plasma. There were no significant changes in heart rate, blood pressure or forced
      expiratory volume in 1 s. 4. These results suggest that an increase in the amount
      of substrate for nitric oxide synthase can increase the formation of endogenous
      nitric oxide. This may have therapeutic relevance in diseases in which there is
      defective production of nitric oxide.

PMID- 7720337
TI  - Serum and platelet-derived growth factor-induced expression of vascular
      permeability factor mRNA by human vascular smooth muscle cells in vitro.
AB  - 1. Endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation
      are key events in the pathogenesis of atherosclerosis. Vascular permeability
      factor (VPF), an endothelial-cell-specific multifunctional cytokine, was recently
      described, and has the potential to contribute to the development of endothelial
      dysfunction. The present study determines whether cultured human VSMCs express
      mRNA for VPF and whether VPF mRNA expression is influenced by human VSMC
      proliferation. 2. A 204 bp cDNA fragment, specific for all known variants of VPF
      mRNA, was cloned and used to demonstrate that human VSMCs express abundant
      quantities of VPF mRNA, whereas human endothelial cells do not. VPF mRNA levels
      were markedly diminished in non-proliferating human VSMCs. In contrast, when
      human VSMCs were stimulated to proliferate by exposure to serum, there was a
      rapid 6.6-fold increase (P < 0.01 versus time 0 h) in VPF mRNA expression, which
      was maximal at 3 h and persisted beyond 24 h. The magnitude of the VPF mRNA
      response in human VSMCs was dependent on the serum concentration. 3. Platelet
      derived growth factor also increased VPF mRNA expression by human VSMCs, thus
      confirming that recognized growth factors for VSMCs also potently influence the
      VPF gene. 4. In conclusion, VPF mRNA is expressed by human VSMCs, the magnitude
      of VPF expression being temporally related to the proliferation of human VSMCs
      and the potency of the growth-promoting stimulus. We propose that VPF produced by
      proliferating human VSMCs could act as a paracrine hormone to powerfully
      influence the permeability and growth of the overlying vascular
      endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720338
TI  - Thrombin does not alter vascular hyporeactivity in models of endotoxin-induced
      septic shock in rats.
AB  - 1. Hypotension and vascular hyporesponsiveness to vasoconstrictors are observed
      during endotoxic shock, and are associated with increased production of nitric
      oxide in the vascular wall. Disseminated intravascular coagulation is another
      feature of septicaemia. We hypothesized that thrombin generated during
      disseminated intravascular coagulation might modulate the changes in vascular
      tone induced by endotoxin. 2. Incubation of rat aortic rings for 4 h with alpha
      thrombin (0.003-3.0 NIH units/ml) did not change their reactivity to
      noradrenaline. Incubation for 4 h with lipopolysaccharide increased the EC50 for
      noradrenaline, whereas co-incubation of thrombin (0.5 NIH units/ml) with
      lipopolysaccharide did not alter this hyporeactivity to noradrenaline. 3. In vivo
      in rats, lipopolysaccharide caused early (1 h) and late (4-6 h) hyporeactivity to
      noradrenaline. In rats infused with lipopolysaccharide and heparin (1 U min-1 kg
      1, 0.4 ml/h) or hirudin (2.2 mg ml-1 kg-1, 0.8 ml/h), vasopressor responses to
      noradrenaline were not different from those after infusion of lipopolysaccharide
      alone. Aortic rings taken from rats receiving both anticoagulant treatment and
      lipopolysaccharide had the same sensitivity to noradrenaline as those obtained
      from rats receiving lipopolysaccharide alone. 4. Our results suggest that, in
      vivo, disseminated intravascular coagulation does not modify the early and late
      effects of lipopolysaccharide on arterial pressure and that, in vitro, thrombin
      neither induces hyporeactivity to noradrenaline nor modifies lipopolysaccharide
      induced hyporeactivity. We propose that thrombin generated during disseminated
      intravascular coagulation in rats does not play a major role in the alterations
      of vascular tone observed during endotoxic shock.

PMID- 7720339
TI  - Brain natriuretic peptide: effect on left ventricular filling patterns in healthy
      subjects.
AB  - 1. Elevated plasma concentrations of brain natriuretic peptide are found in
      conditions associated with impaired left ventricular diastolic function. The
      purpose of this study was to determine whether this peptide actually plays a
      physiological role in improving myocardial performance in diastole. 2. Nine
      normal subjects received infusions of brain natriuretic peptide or placebo in a
      randomized, double-blind, crossover study. Brain natriuretic peptide infusion
      produced a significant reduction in isovolumic relaxation time (means and 95%
      confidence interval for difference -10.8 ms, -14.5 to -7.0 ms) (P < 0.01) and
      significantly increased both the peak E/A velocity (0.54, 0.14-0.94) (P < 0.05)
      and the E/A time velocity integral (1.09, 0.20-1.98) (P < 0.05). 3. These
      responses were evident at concentrations of brain natriuretic peptide that
      produced no associated effects on blood pressure, heart rate or stroke distance.
      4. Brain natriuretic peptide infusion in normal subjects significantly reduces
      isovolumic relaxation time and improves transmitral Doppler flow profiles,
      suggesting that this peptide may be important in the control of left ventricular
      diastolic relaxation in man.

PMID- 7720340
TI  - Haemodynamic and hormonal responses to cardiac pacing in humans: influence of
      different stimulation sequences and rates.
AB  - 1. To examine the effects of rate and pressure on release of vasoactive hormones,
      10 healthy subjects were examined. 2. A standardized pacing protocol was used to
      achieve different haemodynamic responses at two predetermined heart rates.
      Haemodynamic variables, and plasma concentrations of atrial natriuretic peptide,
      arginine vasopressin, adrenaline and noradrenaline were measured. 3. Right
      atrioventricular pacing at a rate of 150 impulses/min resulted in disparate
      responses in right atrial pressure (slight decrease) and pulmonary capillary
      wedge pressure (increase). Change in arterial plasma concentration of atrial
      natriuretic peptide correlated to change in pulmonary capillary wedge pressure,
      and change in arterial plasma concentration of noradrenaline correlated to change
      in total systemic vascular resistance, whereas concentrations of adrenaline and
      arginine vasopressin did not alter significantly during the stimulation periods.
      A significant influence of rate in addition to the pressure related influence on
      plasma concentration of atrial natriuretic peptide was found. In contrast, an
      increase in rate in the absence of an increase in atrial pressures did not raise
      the plasma concentration of atrial natriuretic peptide. There was no significant
      relationship between change in atrial natriuretic peptide and noradrenaline. 4.
      These data support the concept of a rate dependence of atrial natriuretic peptide
      release in man. Increased atrial pressure and thus presumed atrial stretch seems
      to be a prerequisite for increased plasma concentration of atrial natriuretic
      peptide. In addition, these results highlight the importance of monitoring both
      left and right atrial pressure in clinical investigations assessing modulation of
      atrial natriuretic peptide release.

PMID- 7720341
TI  - Haemodynamic effects of continuous positive airway pressure in humans with normal
      and impaired left ventricular function.
AB  - 1. Continuous positive airway pressure increases intrathoracic pressure, thereby
      decreasing left ventricular preload and afterload. We hypothesized that there
      would be a dose-related alteration in cardiac and stroke volume indices in
      response to continuous positive airway pressure in normal subjects and patients
      with congestive heart failure and that the direction of response among those with
      heart failure would be related to left ventricular preload. 2. Cardiac and stroke
      volume indices were measured at baseline and after 10 min of continuous positive
      airway pressure at both 5 and 10 cmH2O (0.5 and 0.99 kPa respectively) in 16
      patients with heart failure and five control subjects with normal cardiac
      function. Among the eight patients with heart failure and elevated pulmonary
      capillary wedge pressure (> or = 12 mmHg) (> or = 1.6 kPa), cardiac index
      increased from 2.47 +/- 0.34 at baseline to 2.91 +/- 0.32 to 3.12 +/- 0.40 l min
      1 m-2 (P < 0.025) while on 5 and 10 cm H2O of continuous positive airway pressure
      respectively. In the same patients stroke volume index increased from 27.8 +/-
      3.9 to 33.9 +/- 4.2 to 36.8 +/- 5.5 ml/m2 (P < 0.05). In contrast, in both the
      control subjects and patients with heart failure and normal pulmonary capillary
      wedge pressure (< 12 mmHg) there was a dose-related decrease in cardiac and
      stroke volume indices while on continuous positive airway pressure. 3. Continuous
      positive airway pressure causes dose-related increases in cardiac and stroke
      volume indices among patients with chronic heart failure and elevated left
      ventricular filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720342
TI  - Regional matching of ventilation and perfusion during lobar bronchial occlusion
      in man.
AB  - 1. Ventilation-perfusion balance in the presence of airway obstruction will
      depend on the efficiency of hypoxic pulmonary vasoconstriction beyond obstructed
      airways and the matching of redistributed blood flow and ventilation to the rest
      of the lung. This study investigated the relative importance of these mechanisms
      in man during experimental bronchial occlusion. 2. The bronchus to the left lower
      lobe was temporarily occluded with a balloon-tipped catheter during fibreoptic
      bronchoscopy in eight supine normal volunteers. Respiratory gas tensions were
      measured within the occluded lobe with a respiratory mass spectrometer. The
      distribution of ventilation and perfusion was assessed under control conditions
      and after 5 min of bronchial occlusion by computer analysis of the regional
      distribution of radioactivity during inhalation of 81mKr gas and following
      injection of 99mTc-labelled macroaggregated albumin respectively. 3. Respiratory
      gas partial pressures within the occluded lobes rapidly stabilized at mixed
      venous gas tensions: PO2 43.4 +/- 2.2 (SEM) mmHg, PCO2 40.2 +/- 1.8 mmHg. During
      occlusions the arterial oxygen saturation fell from a baseline of 96.3 +/- 0.46%
      to a nadir of 92.1 +/- 0.43%. Bronchial occlusion produced underventilation in
      the left lung relative to perfusion, both in the region of the occluded lower
      lobe and at the lung apex. Relative overventilation occurred in the right lung.
      4. It is concluded that arterial hypoxaemia during lobal bronchial occlusion is
      caused primarily by shunting of mixed venous blood, though the shunt fraction is
      reduced by approximately 50% by hypoxic pulmonary vasoconstriction. In lung
      adjacent to obstructed regions reduced compliance may impair ventilation more
      than perfusion to contribute to hypoxaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720343
TI  - Screening tests for microalbuminuria in non-diabetic elderly subjects and their
      relation to blood pressure.
AB  - 1. Microalbuminuria in non-diabetic elderly subjects is predictive of vascular
      disease and mortality, and related to levels of blood pressure. 2. This study was
      designed to examine whether more restricted periods of urine collection retained
      the relation to the prevailing level of blood pressure and successfully
      identified subjects with microalbuminuria. 3. Fifty elderly subjects (aged over
      60 years) made two consecutive 24-h urine collections for measurement of urinary
      albumin excretion, divided between daytime and night-time periods. Thirty-three
      subjects also provided a random 'spot' urine sample. Clinic and 24-h ambulatory
      blood pressure were also recorded. 4. Median 24-h urinary albumin excretion was
      15.75 mg; 17 subjects had microalbuminuria. The median 24-h albumin-creatinine
      ratio was 1.91 mg/mmol. A threshold albumin-creatinine ratio of > or = 3.0
      mg/mmol in a random urine sample predicted microalbuminuria with 92% sensitivity
      and 90% specificity. Alternatively, threshold values of 2.5 mg/mmol for men and
      4.5 mg/mmol for women in an overnight urine collection predicted microalbuminuria
      with 88% sensitivity and 100% specificity. 5. The closest relation between
      albumin-creatinine ratio and blood pressure was that between spot albumin
      creatinine ratio and clinic systolic blood pressure (r = 0.64, P < 0.001).
      Albumin-creatinine ratio was generally related to clinic systolic blood pressure,
      diastolic blood pressure and ambulatory systolic blood pressure. Microalbuminuric
      subjects had significantly higher levels of clinic and ambulatory systolic blood
      pressure than non-microalbuminuric subjects. 6. Microalbuminuria in the elderly
      is most related to clinic systolic blood pressure.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7720344
TI  - Flow motion in peripheral diabetic neuropathy.
AB  - 1. Flow motion is the cyclical variation in blood flow owing to the rhythmical
      opening and closing of arterioles. Previous studies have suggested that cutaneous
      flow motion may be altered in diabetic neuropathy but have not been consistent in
      their findings. 2. In order to assess the effect of diabetic peripheral
      neuropathy on flow motion, we have examined the frequency and amplitude of flow
      motion in 12 patients with diabetic peripheral neuropathy, 10 age-matched
      diabetic patients without peripheral neuropathy and 10 age-matched non-diabetic
      controls. 3. Peripheral neuropathy was diagnosed by a history of foot ulceration
      or chronic painful neuropathy, clinical examination and abnormal peroneal nerve
      conduction velocities. Blood flow, using laser Doppler flowmetry, was measured at
      four sites on the dorsum of both hands and feet. Flow motion was analysed using
      fast Fourier transform analysis, between 0.05 and 0.2 Hz, and displayed on a
      power spectral density graph. Predominant frequency and relative amplitude of
      flow motion were calculated. 4. Relative amplitude and frequency of flow motion
      were similar in the hands of all three groups, as was the frequency in the feet
      of the three groups. Relative amplitude was significantly smaller in the feet of
      diabetic patients with neuropathy (median 7.2%, 95% confidence interval 4.9-9.4%)
      than in diabetic patients without neuropathy (median 13.5%, 95% confidence
      interval 6.3-21.5%, P < 0.02) or in non-diabetic control subjects (median 10.3%,
      95% confidence interval 6.9-27.4%, P < 0.02). 5. Flow motion amplitude is reduced
      in diabetic peripheral neuropathy. The control of flow motion amplitude appears
      to be at least partly under neurological control.

PMID- 7720345
TI  - Acute effect of parathyroid hormone on urine concentration in the rat.
AB  - 1. It has been demonstrated that parathyroid hormone can increase adenylate
      cyclase activity in the rat papilla, produce a small antidiuretic effect and in
      vitro can interfere with the action of arginine vasopressin on water transport.
      Clearance studies were performed in the anaesthetized water diuretic
      thyroparathyroidectomized rat to evaluate further the effect of parathyroid
      hormone on urine concentration in the presence and absence of arginine
      vasopressin. 2. A maximal phosphaturic concentration of rat parathyroid hormone
      (2 micrograms/kg) reduced urine flow from 125 +/- 7 to 81 +/- 9 microliters/min
      within 10 min (P < 0.01). Addition of a maximal antidiuretic concentration of
      arginine vasopressin (100 ng/kg) produced a delayed and diminished antidiuretic
      response when compared with a group of rats not pretreated with parathyroid
      hormone (47 +/- 5 compared with 27 +/- 5 microliters/min; P < 0.01). However, a
      supramaximal arginine vasopressin concentration (1000 ng/kg) produced a maximal
      antidiuretic effect in the presence of parathyroid hormone. 3. To evaluate
      further the inhibitory effect of parathyroid hormone on arginine vasopressin
      induced antidiuresis, parathyroid hormone (2 micrograms/kg) was administered to
      one group of rats and a minimally effective arginine vasopressin concentration
      (7.5 ng/kg) to another group, which produced a similar antidiuretic effect.
      However, the subsequent effect of a maximal antidiuretic arginine vasopressin
      concentration (100 ng/kg) was again significantly blunted in the group pretreated
      with parathyroid hormone. 4. Parathyroid hormone produced only a small increase
      in mean plasma calcium concentration, and glomerular filtration rate was not
      altered by either hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720346
TI  - Prolonged hyperalimentation as a possible cause of renal tubular dysfunction:
      evaluation of 1,5-anhydro-D-glucitol resorption and N-acetylglucosaminidase
      excretion in humans.
AB  - 1. A major polyol found in the sera and other tissues of humans, 1,5-anhydro-D
      glucitol, is mainly ingested in the diet and is excreted in urine. We compared
      the influence of the long-term administration of total parenteral nutrition free
      of 1,5-anhydro-D-glucitol with that of total enteral nutrition on the serum level
      of 1,5-anhydro-D-glucitol in 46 patients who could not take food by mouth. 2. The
      serum concentration of 1,5-anhydro-D-glucitol and its kinetics remained unchanged
      in the group receiving total enteral nutrition (n = 21) over a period of 12
      months. However, after 1 month on total parenteral nutrition (n = 25), the serum
      level of 1,5-anhydro-D-glucitol decreased, falling to about one-sixth the
      pretreatment level in the 12th month. Because the serum level of 1,5-anhydro-D
      glucitol continued to decline, falling below the limit at which its renal
      reabsorption is normally activated, this decrease did not seem to be caused
      directly by a nutritional deficiency of this substance. 3. The urinary excretion
      of 1,5-anhydro-D-glucitol was closely correlated (r = 0.792) with that of N
      acetyl-beta-glucosaminidase; but not with the serum creatinine level or of the
      urinary excretion of microalbumin or of urinary beta 2-microglobulin. We observed
      no glucosuria, hyperuricuria or changes in serum electrolytes during total
      parenteral nutrition. 4. The reduction in the serum level of 1,5-anhydro-D
      glucitol and the urinary excretion of N-acetyl-beta-glucosaminidase were
      correlated with the duration of total parenteral nutrition
      administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720347
TI  - Production of eicosanoids and cytokines by Kupffer cells from young and old rats
      stimulated by endotoxin.
AB  - 1. The clinicopathological features of endotoxaemia have been ascribed to
      cytotoxic mediators such as tumour necrosis factor, interleukins and eicosanoids.
      Macrophages, particularly Kupffer cells, are an important source of these
      mediators. Mortality from endotoxaemia is highly age related. 2. These studies
      focus on the role of hepatic Kupffer cells in the increased sensitivity of old
      rats to bacterial endotoxins. Possible age-related changes in the production of
      eicosanoids and induction of gene expression and secretion of interleukin 1,
      tumour necrosis factor and interleukin 6 were investigated in Kupffer cells
      derived from both young and old animals. 3. Basal production of biological
      response modifiers was low in cells of both young and old rats.
      Lipopolysaccharide stimulated production of the same types of monokines as
      described for other types of macrophages, although the pattern was specific for
      Kupffer cells. 4. Eicosanoids, predominantly prostaglandin D2 and prostaglandin
      F2 alpha, were produced mainly during the first hour after exposure to
      lipopolysaccharide. Endotoxin stimulated synthesis of mRNAs of interleukin 1,
      interleukin 6 and tumour necrosis factor alpha resulting in increased secretion
      of these cytokines into the medium. 5. Kupffer cells from both young and aged
      animals appear to be exquisitely sensitive to endotoxin in respect of expression
      of mRNA for both interleukin 1 alpha and interleukin 1 beta and less sensitive
      with respect to interleukin 6 and tumour necrosis factor alpha gene expression.
      At relatively high lipopolysaccharide concentrations interleukin 6 was secreted
      in particularly large amounts. 6. The effects of ageing on any of these responses
      of Kupffer cells were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720348
TI  - Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100
      in obesity: a stable isotope study.
AB  - 1. We measured the hepatic secretion of very-low-density lipoprotein
      apolipoprotein B-100 (VLDL apoB) using a stable-isotope gas chromatography-mass
      spectrometry method in six obese subjects [three males, three females, age 41.5
      +/- 3.4 years (mean +/- SEM), weight 105.0 +/- 4.8 kg, plasma total cholesterol
      concentration 6.2 +/- 0.4 mmol/l, triacylglycerol 2.8 +/- 0.8 mmol/l, high
      density lipoprotein cholesterol 1.0 +/- 0.2 mmol/l] and six lean control subjects
      (three males, three females, age 41.8 +/- 3.7 years, weight 68.2 +/- 4.9 kg,
      total cholesterol concentration 4.5 +/- 0.3 mmol/l, triacylglycerol 0.8 +/- 0.2
      mmol/l, high-density lipoprotein cholesterol 1.3 +/- 0.1 mmol/l). 2. Plasma total
      cholesterol, triacylglycerol and mevalonic acid (an index of cholesterol
      synthesis in vivo) concentrations were significantly higher in the obese subjects
      than in control subjects (P = 0.02, P = 0.03, P = 0.04, respectively). VLDL apoB
      pool size and absolute secretion rate were significantly higher in the obese
      subjects than in control subjects (323.4 +/- 99.8 mg versus 53.6 +/- 17.1 mg, P =
      0.004; and 42.3 +/- 13.8 mg kg fat-free mass-1 day-1 versus 10.7 +/- 0.4 mg kg
      fat-free mass-1 day-1, P = 0.01), but there was no significant difference in the
      fractional catabolic rate of VLDL apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720349
TI  - Acute stimulation of albumin synthesis rate with oral meal feeding in healthy
      subjects measured with [ring-2H5]phenylalanine.
AB  - 1. The short-term effect of oral feeding on albumin synthesis rate was
      investigated in 12 healthy volunteers using two meal regimens. Albumin synthesis
      was measured over 90 min after injection of a 'flooding' amount (43 mg/kg body
      weight) of phenylalanine enriched to 7.5, 10 or 15 atoms % with the stable
      isotope [ring-2H5]phenylalanine. 2. In one set of subjects, consumption of five
      small hourly meals resulted in a consistent and significant increase (P < 0.05)
      in albumin fractional synthesis rate from a mean (+/- SEM) fasting value of 5.8
      (+/- 0.4)%/day to 7.1 (+/- 0.4)%/day in the fed state. 3. A second study in which
      albumin synthesis was measured 30 min after consumption of a single larger meal
      was carried out in another set of volunteers. The fractional rate of albumin
      synthesis was again significantly elevated after feeding (P < 0.05), rising from
      7.1 (+/- 0.4)%/day in the fasted state to 9.1 (+/- 0.6)%/day in the fed state. In
      both studies, similar responses were observed in the absolute rate of albumin
      synthesis (mg day-1 kg-1). 4. Albumin secretion time was significantly shorter (P
      < 0.05) after feeding in both studies, suggesting that the acute stimulation in
      albumin synthesis observed after feeding may in part be mediated via a post
      transcriptional mechanism. 5. The response of total liver protein synthesis to
      oral feeding was investigated in an animal model employing adult rats studied
      with a flooding amount of [2,6-3H]phenylalanine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720350
TI  - Measurement of intestinal calcium absorption by using stable strontium.

PMID- 7720351
TI  - [Evaluation of 3 calculation methods to compute the PER, PFR, TPER, TPFR with
      equilibrium radioisotopic angiocardiography].
AB  - The author wanted to test 3 FITS to compute the peak ejection rate, the time of
      the peak ejection rate, the peak filling rate, the time of the peak filling rate
      from the left ventricle volume curve computed by means of the multigated radio
      nuclide angiography; the aim of the test was to ascertain the differences between
      the 3 methods and the differences between them for medical applications. 25
      patients were tested and they were divided as follows: 5 cases of hypertension, 2
      cases of obesity, 9 cases of alimentary diabetes, 3 cases of coronary heart
      disease, 6 cases with other diseases. The investigated FITS were: 1) the FIT that
      computes the derivative curve of the volume curve; 2) the FIT that computes the
      derivative equation of the volume curve and that interpolates it to a polynomial;
      3) the FIT of Fourier. A discriminant analysis was performed and the following
      observations were made: according to a significant probability P < 0.05, FIT 1
      classified 40% of the cases, FIT 2 classified 48% of the cases, FIT 3 classified
      64% of the cases. A Box's M test was performed and was significant for FIT 3 and
      FIT 2 but not for FIT 1. In conclusion the test of the 3 FITS showed that FIT 3
      is a better discriminant between the diverse diseases.

PMID- 7720352
TI  - [Juvenile dyslipidemia as early risk factor for atherosclerosis. Analysis of a
      sample of school age boys].
AB  - Atherosclerosis appears already in the first years of life. Several factors may
      accelerate the age of onset and the gravity of its symptoms. Particular
      importance is attributed to lipid metabolism in youth. Ther Authors studied the
      rates of cholesterol, HDL, LDL, triglycerides, apolipoproteins AI and B100,
      lipoprotein a and several anamnestic and anthropometric parameters in a group of
      103 young people of Rome, between 16 and 19 years of age. They processed these
      data statistically and compared them with those of a similar American group. The
      results showed a tendency to fatness in the Italian sample, and to dyslipidosis
      in the American group. Besides, the subjects who had been breast-fed presented
      higher blood levels of cholesterol and apolipoprotein B100.

PMID- 7720353
TI  - [Propafenone and verapamil poisoning. Report of 2 clinical cases].
AB  - We described the self-poisoning of two young adolescents who took improper doses
      of two major cardiovascular drugs: propafenone and verapamil. The young girls
      developed markedly different clinical patterns: ECG abnormalities without
      clinical consequences were found in one case progressively ingravescent ECG
      abnormalities leading to cardiac arrest in the other. These differences are
      probably due to varying doses taken and metabolic states. Conventional
      detoxication and resuscitation techniques proved successful in both cases.

PMID- 7720354
TI  - [Intra-articular treatment with somatostatin 14 in rheumatoid arthritis].
AB  - 19 patients with RA underwent six intraarticular injections of 750 micrograms of
      Somatostatin 14 in one knee at 15-day intervals. In all patients some clinical
      parameters were evaluated: articular function, pain on pressure, spontaneous
      pain, pain on movement, duration of morning stiffness. Also some laboratory
      parameters were examined: complete blood cell count, ESR and CRP. An overall and
      significant improvement of the symptomatology of the treated knee was seen in all
      patients especially after the 3rd infiltration and still more after the 5th. At
      follow up 3 months after the end of treatment 12 patients were controlled, 11 of
      these showed a persistence of the improvement. No side-effects were seen.

PMID- 7720355
TI  - [Evaluation of the total hepatic function after treatment with fosinopril in
      hypertensive patients with liver cirrhosis].
AB  - Fosinopril is distinguished from other ACE inhibitors by a pharmacokinetic
      pecularity in the sense that is can be metabolized either by liver or kidney.
      This was the rationale of the present research the aim of which was to verify if
      administered to patients with liver cirrhosis the drug was liable to alter global
      liver function and ability to metabolize drugs. Eight cirrhotic males, mean age
      56 years, also suffering from high blood pressure, were studied. In these
      patients, liver and kidney function tests (BUN, creatinine blood level, serum and
      urinary electrolytes, creatinine clearance, calcium and phosphor blood level,
      transaminases, alkaline phosphatase prothrombin time, cholinesterase, gamma
      glutamyl-transpeptidase) were carried out at baseline and after 30 days'
      fosinopril treatment (1 capsule every morning in the fasting state); in addition
      total functioning liver mass was assessed by the galactose test, and drug
      metabolizing capacity by the antipyrine test. Treatment resulted in a significant
      improvement of pressure values in all patients (p < 0.01) and did not alter liver
      and kidney function parameters. Besides, no side effects were registered,
      especially no case of orthostatic hypotension. The antipyrine test was not
      influenced by fosinopril treatment. Therefore, short-term treatment with this ACE
      inhibitor can be concluded to be effective and not to cause additional
      alterations of liver function in patients with liver cirrhosis.

PMID- 7720356
TI  - [Pertussis].
AB  - A synthesis concerning whooping cough is presented with the object of taking
      stock of the situation regarding the pediatric disease which, in spite of
      developments in antibiotic therapy and vaccine prophylaxis is still a cause for
      series concern in view of its all but rare complications, especially in infants
      of less than one year, and of the uncertainties surrounding the validity of
      specific vaccines. An up-date on this is certainly not superfluous, especially
      now when we are at a true turning point in prophylaxis with the use of acellular
      vaccines obtained by genetic enegenering. This is particularly interesting for
      the practitioner who is in direct contact with the actual situation.

PMID- 7720357
TI  - [Chronic obstructive bronchopneumopathy. Epidemiologic aspects and balneotherapy
      potential].
AB  - The authors remember the epidemiological data of BPCO in Italy and in the world
      and stress the increasing incidence and prevalence of these disease, interesting
      above all industrial-urban areas, middle and old aged, males and smokers. The
      pathogenetic role of atmospheric pollution, caused by industries, heating system
      and motor vehicles, in exposed. At the end Auctors summarise the results of the
      inhalatory therapy by mineral waters in BPCO, especially of sulphureas and salso
      jodic spas.

PMID- 7720358
TI  - [The use of various serotoninergic agents that regulate feeding behavior].

PMID- 7720359
TI  - [Back to school: vision problems].

PMID- 7720360
TI  - Constraints on perceptual learning: objects and dimensions.
AB  - The article addresses two questions about perceptual learning: What are the
      circumstances which produce learning? What is the content of learning? For each
      question, a critical principle is suggested: (1) Objects are constrained to
      behave in certain ways. If a violation is detected, an internal malfunction is
      assumed and subsequently corrected. (2) Learning involves mappings between entire
      perceptual dimensions rather than associations between individual stimuli. The
      principles are applied to two phenomena: the classic adaptation to prism
      distorted vision and the more recent, but equally elusive, McCollough effect. The
      view suggests a new interpretation of the McCollough effect and accounts for
      findings difficult to account for in other interpretations including which
      stimuli can successfully lead to contingent after-effects, the outcome of
      correlation manipulations, and why the effect exists at all. In addition, the
      phenomenon is linked to prism adaptation, usually regarded as a distinct type of
      plasticity. In general, the view advanced is that the two principles help
      distinguish perceptual learning from other types of learning processes.

PMID- 7720361
TI  - The role of covariation versus mechanism information in causal attribution.
AB  - Traditional approaches to causal attribution propose that information about
      covariation of factors is used to identify causes of events. In contrast, we
      present a series of studies showing that people seek out and prefer information
      about causal mechanisms rather than information about covariation. Experiments 1,
      2 and 3 asked subjects to indicate the kind of information they would need for
      causal attribution. The subjects tended to seek out information that would
      provide evidence for or against hypotheses about underlying mechanisms. When
      asked to provide causes, the subjects' descriptions were also based on causal
      mechanisms. In Experiment 4, subjects received pieces of conflicting evidence
      matching in covariation values but differing in whether the evidence included
      some statement of a mechanism. The influence of evidence was significantly
      stronger when it included mechanism information. We conclude that people do not
      treat the task of causal attribution as one of identifying a novel causal
      relationship between arbitrary factors by relying solely on covariation
      information. Rather, people attempt to seek out causal mechanisms in developing a
      causal explanation for a specific event.

PMID- 7720362
TI  - Processing separable complex verbs in Dutch: comments on Frazier, Flores
      d'Arcais, and Coolen (1993)

PMID- 7720363
TI  - Testing for skin sensitization according to the notification procedure for new
      chemicals: the Magnusson and Kligman test.
AB  - The notification procedure for new chemicals in the European Union (called the
      Chemicals Act in Germany) requires a skin sensitization test when the amount of a
      new chemical produced exceeds 100 kg/year. The preferred test is that of
      Magnusson and Kligman; more than 90% of the tests submitted are performed with
      it. Though the Magnusson and Kligman test is described in the literature, and in
      the test guidelines of the European Union and of the OECD, discrepancies do occur
      in the performance of the test between test laboratories. In this paper,
      recommendations are given for standardized performance of the Magnusson and
      Kligman test.

PMID- 7720364
TI  - Contact urticaria with anaphylactic reactions caused by occupational exposure to
      iridium salt.
AB  - This paper presents the case of a non-smoking and non-atopic male, exposed to
      iridium chloride at work, who developed respiratory tract symptoms and contact
      urticaria. Application of iridium salt to normal skin caused contact urticaria.
      An iridium chloride prick test showed a positive reaction and a scratch test
      produced anaphylactoid reactions. Platinum salt allergy was excluded through
      prick testing with hexachloroplatinate solution. There is no previous report
      describing a case where an individual has a positive prick test reaction to
      iridium salts and simultaneously a negative one to platinum salts. The results
      are interpreted as immediate-type hypersensitivity (Type I allergy?) to iridium
      salt. The route of sensitization was probably through the airways. Further
      testing showed that iridium salt allergy could persist for at least 18 months
      after exposure ceases. 14 employees at the same factory were prick tested with
      iridium and platinum salts with negative results. Prick testing is recommended as
      a method of first choice when investigating a person with suspected iridium salt
      allergy.

PMID- 7720365
TI  - The fragrance mix and its constituents: a 14-year material.
AB  - Results from 14 years of patch testing with the fragrance mix and its
      constituents are reviewed. From 1979-1992, 8215 consecutive patients were patch
      tested with the fragrance mix and 449 (5.5%) had a positive reaction. An increase
      in the frequency of reactions to fragrance mix was seen from the first 5-year
      period to the last. Only 54.4% of the patients tested in the last 5-year period
      with the individual constituents of the mix had at least 1 positive reaction. The
      results of testing with the constituents are the basis for a discussion of
      methodological problems. A significant decrease in the frequency of reaction to
      cinnamic aldehyde was registered, at the same time as the test concentration was
      reduced from 2% to 1% pet. However, no significant variations in the frequency of
      reactions to oak moss were seen, notwithstanding a similar reduction in test
      concentration.

PMID- 7720366
TI  - Occupational allergic contact dermatitis from alkanolamineborates in metalworking
      fluids.
AB  - Alkanolamineborates are extensively used in coolants as corrosion inhibitors. In
      this paper, 3 machinists with contact allergy to alkanolamineborates are
      reported. To avoid false-positive test reactions due to the alkalinity of the
      alkanolamineborates, they should be tested when dissolved in an acidic buffer.
      When various alkanolamineborates were tested in dilution series in the 3
      patients, 2 types of reactivity patterns emerged, indicating the existence of at
      least 2 separate sensitizers in alkanolamineborates. The raw materials,
      ethanolamines and boric acid, did not yield any positive patch test reactions.
      Thin-layer chromatography investigations demonstrated that each
      alkanolamineborate consists of many substances, which differed in part between
      different alkanolamineborates. The present study shows that it is not possible to
      use 1 particular alkanolamineborate for tracing contact allergy to
      alkanolamineborates in general.

PMID- 7720367
TI  - Contents of methyl-, ethyl-, propyl-, butyl- and benzylparaben in cosmetic
      products.
AB  - The contents of methyl-, ethyl-, propyl-, butyl- and benzylparaben in 215
      cosmetic products have been determined to elucidate the concentration and
      frequency of use of these parabens in cosmetic products, and to monitor whether
      the products complied with the Danish and EEC regulations. The results showed
      that 77% of the products investigated contained 0.01%-0.87% parabens. Nearly all
      (99%) of the leave-on cosmetics and 77% of rinse-off cosmetics were found to
      contain parabens. A maximum of 0.32% methyl- and propylparaben, 0.19%
      ethylparaben, and 0.07% butyl- and benzylparaben were present in paraben-positive
      cosmetics. A preferential use of methyl-/ethyl-/propyl-/butyl-/benzylparaben in
      various groups of cosmetic products was revealed.

PMID- 7720368
TI  - Sulfur spring dermatitis.
AB  - 44 cases of an unusual condition, designated hot spring dermatitis, have been
      studied. Patients usually presented during the winter months with a history of
      having taken green sulfur spring baths within the previous 2-20 days. Skin
      lesions developed about 24 h after bathing and were distributed generally over
      the trunk and limbs, especially in the skin folds. No micro-organisms were found
      in either hot spring water specimens or skin lesions. Patch tests showed no
      positive reactions. Investigations were undertaken to determine the
      physicochemical characteristics of the hot spring. In its extreme acidity and
      high content of soluble sulfur and chloride, it differed from other nearby hot
      springs.

PMID- 7720369
TI  - Factors associated with skin irritation of the hands experienced by general
      dental practitioners.
AB  - Practising dental surgeons are now wearing gloves for longer periods of time than
      any other comparable group. As part of a study to assess dentists' attitudes to
      cross-infection, a questionnaire was sent to 1950 randomly selected general
      dental practitioners in England and Wales, with information being requested
      concerning the incidence of skin irritation of the hands considered to be
      associated with glove wearing. The response to the questionnaire was 61%, with
      29% of respondents indicating that they experienced skin irritation. A strong
      association was identified between pattern of glove wearing and incidence of skin
      irritation, with routine glove wearers being more likely to suffer skin
      irritation than occasional glove wearers. Female respondents were also more
      likely to have experienced skin irritation than male respondents. No association
      was identified between reported incidence of skin irritation and practising
      arrangements, years since graduation and number of years of glove wearing.

PMID- 7720370
TI  - Skin disease and contact sensitivity in house painters using water-based paints,
      glues and putties.
AB  - A dermatologic investigation of 202 construction painters included patch testing
      with the TRUE Test standard series and ingredients of water-based paints, glues
      and putties (painters' series). 32 painters had current eczema and 16 had a
      history of previous eczema. Of these, 16 and 9, respectively, had current and
      previous histories of hand eczema. Irritant reactions on the hands, characterized
      by dry, erythematous finely fissured skin, which healed within a few days of skin
      rest, were found in 18 painters. 8 painters presented dry, fissured finger tips
      and finger sides. The total group of painters had 25 allergic reactions to the
      TRUE Test standard series and 11 to the painters' series. 11 test reactions were
      found to be related to present or previous hand eczema: 4 cases reacted to
      nickel, cobalt, colophony or N-octyl-isothiazolinone; 2 each to p-tertbutylphenol
      formaldehyde resin and benzisothiazolinone (BIT); and 3 to Cl + Me
      isothiazolinone. 5 painters were sensitive to BIT without clinical symptoms of
      skin disease. Hand eczema is no more common among construction painters who work
      with water-based paints, glues and putties, than in an average population. There
      are, however, special risks of sensitization and eczema in a construction
      painter's work that should be considered on employment.

PMID- 7720371
TI  - An occupational mark of screwdriver operators.

PMID- 7720372
TI  - 'Fiddler's fingers': violin-string dermatitis.

PMID- 7720373
TI  - Effect of allergic contact dermatitis on wound healing.

PMID- 7720374
TI  - Occupational sensitization to aminopenicillins with oral tolerance to penicillin
      V.

PMID- 7720375
TI  - Metal content of Slovak coinage.

PMID- 7720376
TI  - Maleated soybean oil, a new cosmetic allergen.

PMID- 7720377
TI  - Skin testing with gold sodium thiomalate and gold sodium thiosulfate.
AB  - Recently gold sodium thiosulfate was found to be the most common sensitizer after
      nickel sulfate in our routinely patch tested dermatitis patients. When patients
      hypertensive to gold sodium thiosulfate were tested with another monovalent gold
      salt, gold sodium thiomalate, at equimolar concentrations, in principle, no
      positive reactions were obtained. Gold sodium thiomalate is used for treatment of
      rheumatoid arthritis, a treatment with a high frequency of adverse skin
      reactions. To investigate whether the reactivity difference between the 2 gold
      salts was due to differences in bioavailability, some experiments were carried
      out. Intracutaneous tests with the 2 gold salts at equimolar concentrations
      yielded equivalent reactions. When the concentration of gold sodium thiomalate
      for epicutaneous testing was increased, all 12 gold-allergic patients reacted
      positively. Therefore, in our department, contact allergy to gold sodium
      thiomalate is probably as common as contact allergy to gold sodium thiosulfate.

PMID- 7720378
TI  - Allergic contact dermatitis from retinoic acid.

PMID- 7720379
TI  - The frequency of lanolin contact allergy.

PMID- 7720380
TI  - Photocontact dermatitis from ketoprofen with an unusual clinical feature.

PMID- 7720381
TI  - Hypersensitivity to 2-(2-butoxyethoxy)ethanol.

PMID- 7720382
TI  - Contact allergy to cinnamic aldehyde and cinnamic alcohol in Oleophytal.

PMID- 7720383
TI  - A case of contact dermatitis from lichens in southern Germany.

PMID- 7720384
TI  - Contact dermatitis due to an emulsifying agent in a baker.

PMID- 7720385
TI  - Skin sensitivity to endoprosthetic materials in the recipients of hip prostheses.

PMID- 7720386
TI  - Allergic contact dermatitis from colour developers.

PMID- 7720387
TI  - Airborne contact urticaria due to mulberry (Morus alba) pollen.

PMID- 7720388
TI  - Pesticide patch testing: California nursery workers and controls.

PMID- 7720389
TI  - Contact allergy to cinnoxicam.

PMID- 7720390
TI  - Contact allergy to kojic acid in skin care products.
AB  - Kojic acid (5-hydroxy-2-(hydroxymethyl)-4-pyrone), a fungal metabolic product,
      has increasingly been used as a skin-depigmenting agent in skin care products
      marketed in Japan since 1988. In order to determine its frequency of
      sensitization, during 1 year from October 1992 to September 1993, we performed
      patch testing with it in 220 female patients with suspected cosmetic-related
      contact dermatitis. Of the 220 patients, 8 used at least 1 skin care product
      containing kojic acid, 5 of whom reacted to kojic acid as well as to 1 or more
      their own products containing 1% kojic acid, but not to their other products not
      containing it, and 3 of whom were negative to kojic acid and all their own
      products. Patch testing with kojic acid in the remaining group of 212 patients,
      who had not previously used skin care products containing it, was negative
      without exception. The 5 kojic-acid-sensitive patients, aged 34 to 58 years,
      developed facial dermatitis 1-12 months after starting application of kojic-acid
      containing products. Kojic acid is considered to have high sensitizing potential,
      as a comparatively high frequency of contact sensitivity was observed in patients
      using products containing it (5 out of 8).

PMID- 7720391
TI  - Effect of topically administered platelet-derived growth factor on corneal wound
      strength.
AB  - Since the cornea is an avascular tissue, the wound healing process is lengthy,
      with a need for sutures to stabilize the wound for a long time. Platelet-derived
      growth factor (PDGF) has been shown to accelerate wound healing in rat dermal
      models. Accelerated healing, if unaccompanied by side effects may reduce suture
      related complications such as astigmatism and infectious keratitis. This study
      evaluated the effect of PDGF on wound strength in corneal laceration and
      penetrating keratoplasty models using New Zealand white albino rabbits. Twenty
      two rabbits were used in the corneal laceration model and sixteen rabbits in the
      penetrating keratoplasty model. The treated rabbits received 385 picomoles/drop
      of PDGF-BB dissolved in balanced salt solution six times on day 1 and three times
      a day for the remainder of the study. The control rabbits received balanced salt
      solution in the same dosing schedule. The pressure required to rupture the wound
      was measured using a pressure transducer. In the laceration model the PDGF
      treated group had mean (+/- standard deviation) average pressures on day 7 of 360
      +/- 102 mm Hg for wound rupture compared to 210 +/- 102 mm Hg in the control
      group. (p = 0.005). The average pressures in the penetrating keratoplasty model
      on day 17 were 707 +/- 201 mm Hg for the controls and 1042 +/- 292 mm Hg for the
      PDGF treated group (p = 0.026). Histopathological evaluation of eyes not
      subjected to bursting showed increased fibroblasts at the wound junction with an
      increase in types III and type IV collagen production.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7720392
TI  - Comparison of retinal lesions in alloxan-diabetic rats and galactose-fed rats.
AB  - Galactose-fed rats develop a retinal microvascular disease, but retinopathy has
      not been found to develop reproducibly in diabetic rats. We sought to determine
      which retinal lesions can be reproducibly produced by long-term diabetes in rats,
      the extent to which the capillary lesions in diabetic rats and galactosemic rats
      are similar, and whether the retinopathy induced by 50% galactose can be
      reproduced satisfactorily by a lower concentration of galactose. Alloxan-diabetic
      rats and rats fed either a 50% galactose diet or a 30% galactose diet were killed
      after comparable durations of study (18 to 22 months). Rats fed 50% galactose
      showed greater than normal frequency of retinal pericyte ghosts and acellular
      capillaries, and thickening of capillary basement membranes by 18 months of
      galactosemia. Rats eating 30% galactose developed similar retinal lesions, and
      tended to be healthier than rats fed 50% galactose. Diabetes of 1 1/4 years or
      more likewise resulted in retinal pericyte ghosts, acellular capillaries and
      thickened capillary basement membrane. IRMAs and other vascular abnormalities
      were not reproducibly demonstrated at this duration of study, and saccular
      microaneurysms were not seen in any groups. In a number of diabetic rats, the
      severity of diabetes diminished spontaneously (after 1 to 1 1/2 years of insulin
      deficiency), thus making it essential that glycemia be systematically monitored.
      Both diabetic rats and experimentally galactosemic rats develop microvascular
      lesions that are consistent with at least the early stages of diabetic
      retinopathy, and these models should be useful to screen potential therapies for
      their ability to inhibit the development of retinopathy.

PMID- 7720393
TI  - Melanin can deplete immunosuppressive substances from the aqueous humor.
AB  - Heavily pigmented eyes tend to experience greater inflammation than lightly
      pigmented eyes following trauma and surgery. The purpose of these studies was to
      test the possibilities that: (i) melanin augments T cell-responses by depleting
      or neutralizing anti-inflammatory substances that are normally present in the
      aqueous humor, and (ii) melanin augments extraocular T cell-mediated inflammatory
      responses. Two types of experiments were performed. First, the capacity of
      melanin-adsorbed and non-adsorbed rabbit aqueous humor to inhibit the
      proliferative response of the T cell line D10.G4.1 to IL-1 was tested. Non
      adsorbed aqueous humor inhibited T cell proliferation to the background level in
      unstimulated cultures, whereas melanin-adsorbed aqueous humor enhanced the
      proliferation of stimulated, but not resting T cells. Next, mice were sensitized
      to the antigen conalbumin, and challenged in the ear pinna with conalbumin alone,
      conalbumin + melanin, or melanin alone and delayed-type hypersensitivity (DTH)
      was measured. Challenge with melanin alone caused some ear swelling, and melanin
      increased the DTH response to conalbumin. Our findings are consistent with the
      notion that melanin can augment intraocular inflammation by depleting or
      neutralizing the inhibitory components of normal aqueous humor, possibly exposing
      stimulatory components that are normally masked.

PMID- 7720394
TI  - Efficacy of tobramycin drops applied to collagen shields for experimental
      staphylococcal keratitis.
AB  - Treatment of staphylococcal keratitis includes tobramycin drops at repeated
      intervals, a prolonged therapy that is disruptive to the patient. To identify a
      regimen involving less frequent drug application, we compared the efficacy of
      fortified tobramycin (1.36%) administered by collagen shields or in topical drop
      form to rabbit corneas intrastromally infected with staphylococci. Eyes were
      treated with shields hydrated in and supplemented with fortified tobramycin drops
      (1.36%) applied every 1, 2, 5, or 10 h, from 10 to 20 h postinfection. For
      topical drop treatment alone, tobramycin was applied following the identical
      regimen. Untreated corneas contained 10(6) colony forming units. Shields
      supplemented with tobramycin drops applied every 1, 2, or 5 h sterilized 100% of
      the corneas. Shields supplemented with tobramycin drops applied at 10 h
      sterilized 58% of the corneas. Topical delivery of tobramycin every h sterilized
      all corneas; drops alone applied at longer intervals, such as 2, 5, or 10 h,
      sterilized 83%, 17%, and 0% of the corneas, respectively. Collagen shield
      delivery of tobramycin with supplemental topical drops can eradicate
      staphylococci in this model with less frequent dosing intervals than are required
      with topical therapy alone.

PMID- 7720395
TI  - Alpha-A crystallin: quantitation of C-terminal modification during lens aging.
AB  - Previous studies have demonstrated that the C-terminal region of alpha-A
      crystallin is susceptible to age-dependent, posttranslational modification. To
      quantitate the amount of modification, alpha-A crystallin was purified from total
      proteins of the aging bovine lens, then digested with lys-C endoproteinase.
      Reverse phase, high pressure liquid chromatography was used to resolve and
      quantitate the resulting peptides, to determine the amount of C-terminal peptide
      relative to peptides from other regions of the protein that have not been
      reported to undergo modification. The results indicate that relative to alpha-A
      crystallin from newborn lens, posttranslational modification has occurred in
      approximately 45-55% of the C-terminal region from mature lens. These results
      demonstrate extensive modification of the C-terminal region of alpha-A crystallin
      from the mature lens, indicating that during the aging process, posttranslational
      modifications in this region may make significant contributions to the aggregated
      state and/or molecular chaperone properties of the molecule.

PMID- 7720396
TI  - TGF-beta 1 induces lens cells to accumulate alpha-smooth muscle actin, a marker
      for subcapsular cataracts.
AB  - Spindle-shaped myofibroblast-like cells, which contain alpha-smooth muscle actin,
      have been described in anterior subcapsular cataract and after-cataract. In a
      previous study in this laboratory, it was shown that transforming growth factor
      beta (TGF beta) induces the formation of spindle-shaped cells in lens epithelial
      explants. The aim of this investigation was to determine whether these TGF beta
      induced spindle-shaped cells contain alpha-smooth muscle actin. Lens epithelial
      explants were prepared from 21-day-old rats and cultured with either TGF beta 1
      or basic FGF alone, a combination of both growth factors, or without added growth
      factors. After three days, cellular changes were monitored by phase contrast
      microscopy, localisation of filamentous actin with rhodamine-phalloidin, and
      immunolocalisation and immunoblotting of alpha-smooth muscle actin. TGF beta
      induced rapid cell elongation and formation of characteristic spindle-shaped
      cells in lens epithelial explants in the presence or absence of FGF. These cells
      contained alpha-smooth muscle actin, a marker for myofibroblastic cells and a
      protein not normally found in the lens. The present study thus provides molecular
      evidence that TGF beta induces cataractous changes in lens epithelial cells. As
      TGF beta is potentially available to lens cells in situ throughout life, these
      findings are consistent with a key role for TGF beta in the aetiology of major
      forms of subcapsular cataract.

PMID- 7720397
TI  - Abnormalities of retinal metabolism in diabetes or galactosemia. II. Comparison
      of gamma-glutamyl transpeptidase in retina and cerebral cortex, and effects of
      antioxidant therapy.
AB  - Levels of the intracellular antioxidant, glutathione, become subnormal in retina
      in diabetes or experimental galactosemia. In order to investigate the cause and
      significance of this abnormality, activity of gamma-glutamyl transpeptidase (an
      enzyme important in the synthesis and degradation of glutathione) and levels of
      reduced glutathione have been measured in retinas of diabetic rats and dogs and
      of experimentally galactosemic rats and dogs. Retinal gamma-glutamyl
      transpeptidase activity and glutathione level were significantly less than normal
      after 2 months of diabetes or galactosemia. In contrast, cerebral cortex from the
      same diabetic rats and galactosemic rats showed no significant reduction in
      either gamma-glutamyl transpeptidase activity or glutathione level. These
      different responses of the two tissues to hyperglycemia might help account for
      the difference in microvascular disease in these two tissues in diabetes.
      Consumption of the antioxidants, ascorbic acid (1.0%) plus alpha-tocopherol
      (0.1%), by diabetic rats and galactosemic rats inhibited the decrease of gamma
      glutamyl transpeptidase activity and glutathione levels in retina, suggesting
      that defects in glutathione regulation in the retina are secondary to
      hyperglycemia-induced 'oxidative stress'.

PMID- 7720398
TI  - The effect of a modified beta-cyclodextrin, SBE4-beta-CD, on the aqueous
      stability and ocular absorption of pilocarpine.
AB  - In the present study, the effects of a novel, modified beta-cyclodextrin
      derivative (SBE4-beta-CD; a variably substituted sulfobutyl ether of beta
      cyclodextrin with an average degree of substitution of four) on the aqueous
      stability of pilocarpine and on its ocular absorption in albino rabbits were
      studied. For stability reasons, commercial pilocarpine eyedrops are formulated at
      pH 4-5, a pH range where pilocarpine (pKa approximately 7) is almost completely
      ionized. As shown in the present and past studies, increasing the pH of the
      pilocarpine solution from 4.5 to 7.0 increases the ocular absorption of
      pilocarpine. SBE4-beta-CD increased the aqueous stability of pilocarpine (0.36
      mM) at pH 7.0 (4 degrees C, projected values from Arrhenius data at 25 degrees C,
      37 degrees C and 50 degrees C); in the absence of SBE4-beta CD, t90% was 236
      days. In the presence of 1 mM and 25 mM of SBE4-beta-CD, t90% was 382 days and
      2054 days, respectively suggesting that indeed, pilocarpine does interact with
      SBE4-beta-CD. SBE4-beta-CD did not damage the corneal epithelium in vitro and was
      well-tolerated by the rabbit eye in vivo. Coadministered SBE4-beta-CD did not
      significantly affect the miotic response of pilocarpine solutions at pH values of
      4.5 or 7.0 when the molar ratio of SBE4-beta-CD to pilocarpine was between 0.2:1
      7:1. The effect of the coadministered SBE4-beta-CD on the miotic response of
      pilocarpine solutions was also compared to that of 2-hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) which has recently been suggested to increase ocular
      bioavailability of pilocarpine in rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720399
TI  - Adrenergic and nitrergic neurotransmitters are released by the autonomic system
      of the pig long posterior ciliary artery.
AB  - The role played by adrenergic, muscarinic and nitric oxide putative
      neurotransmitters released from autonomic nerve endings onto the pig proximal
      long posterior ciliary artery (LPCA) was determined. The proximal LPCA in the pig
      usually supplies both the uveal and retinal circulations. In this study, in vitro
      ring segments of the artery, passively stretched and with noradrenaline-induced
      tone, were neurogenically stimulated (NS) using electrical field stimulation with
      5-sec trains of 0.2 msec pulses. NS produced a frequency dependent contraction in
      all vessels which was completely abolished by 10(-6) M tetrodotoxin. 40 Hz
      stimulation was used throughout the study as it produced a maximal NS
      contraction. 10(-5) M guanethidine abolished the NS-induced contraction and
      revealed a NS-induced relaxation, as did the alpha adrenergic blocker,
      phentolamine, in vessels passively stretched. The beta adrenergic blocker,
      propranolol, only slightly reduced the NS-induced constriction. In vessels pre
      contracted with noradrenaline, NS produced a relaxation (D) which was
      proportional in magnitude to the tone (C) viz. D = (0.30 +/- 0.04).C + (0.24 +/-
      0.06). The muscarinic blocker, atropine, had no effect on the NS-induced
      relaxation, implying that it is a non-adrenergic, non-cholinergic mediated
      system. Incubation with Nw-nitro-L-arginine methyl ester reduced the NS-induced
      relaxation to 48% of its control value, a reduction which was reversed in the
      presence of excess L-arginine. Damage to endothelial cell function did not reduce
      the NS-induced relaxation. It is concluded that the autonomic innervation of the
      proximal LPCA releases both contraction and relaxation neurotransmitters.
      Contraction is mediated by an alpha adrenergic neurotransmitter. At least two
      neurotransmitters mediate relaxation, one of which is probably nitric oxide.
      There is no functional evidence for the release of beta adrenergic
      neurotransmitter from the sympathetic system or acetylcholine from the
      parasympathetic system.

PMID- 7720400
TI  - Steroid inhibition of limbal blood and lymphatic vascular cell growth.
AB  - Steroids are widely used in the prevention of corneal neovascularization in a
      wide range of natural and experimental situations. However, no information is
      available on their effect on the growth of the individual limbal blood vascular
      cells or of lymphatic cells involved in corneal neovascularization. In addition,
      tritiated thymidine labelling index is commonly used as an indicator of cell
      population but doubt exists as to whether it truly represents cell growth. Remote
      thermal cautery of the rat cornea was used to elicit corneal neovascularization.
      New cell growth was measured by tritiated thymidine uptake and by the number of
      cell nuclei per section. Cells investigated were the arteriolar, venular,
      capillary and lymphatic endothelial cells as well as the arteriolar and venular
      perivascular cells. A total of 89,320 blood vascular endothelial and perivascular
      cell nuclei and 12,075 lymphatic nuclei were counted. Thermal cautery elicited a
      significant increase in labelling index and cell population of all limbal
      vascular cell types. Steroid application elicited a significant short term
      inhibition or delay for all six cell types although this was not apparent for
      venular endothelial cells using labelling index as a growth indicator. At six
      days only the lymphatic endothelial cell population showed a significant (p <
      0.001) increase associated with steroid use.

PMID- 7720401
TI  - Chromosomal locations of the genes for the beaded filament proteins CP 115 and CP
      47.
AB  - We have used the polymerase chain reaction (PCR) to amplify CP 115 and CP 47
      encoding sequences from human lens cDNA samples. DNA sequence and northern blot
      analysis were used to confirm human origin. From the determined cDNA sequences,
      human-specific oligonucleotides were synthesized and assessed for the ability to
      amplify human genomic DNA. After empirically selecting a primer pair for each
      gene able to amplify human genomic DNA, and optimizing PCR conditions for human
      specificity, we used the PCR to screen a panel of mouse/human somatic cell hybrid
      DNA samples. Amplification of CP 115 or CP 47 sequences in each of the somatic
      cell hybrid samples was correlated with the presence/absence of human genomic DNA
      sequences encoding the respective gene sequences. From our results, we conclude
      that the gene for human CP 115 resides on chromosome 20 and the gene for human CP
      47 on chromosome 3. Further mapping using somatic cell lines carrying derivatives
      of human chromosome 3 localize the gene for CP 47 to 3q21-25. We propose LIFL-H
      (Lens Intermediate Filament Like-Heavy) for CP 115 and LIFL-L (Lens Intermediate
      Filament Like-Light) for CP 47 as the gene symbols for these loci.

PMID- 7720402
TI  - Measurement error in assessing the size of cortical cataracts from
      retroillumination photographs.
AB  - This study describes a new method of quantifying anteriorly located cortical
      cataracts using retroillumination photographs and computer planimetry. Cortical
      cataracts were graded clinically and then photographed using the Neitz
      retroillumination camera twice by each of 2 photographers. The cataract outlines
      were traced onto a transparent overlay, and computer planimetry was performed
      using a Scan Maker 600ZS, a MAC II Computer and specially developed software. We
      estimated the measurement error of the method and its associated effect on sample
      size estimates for clinical studies. We calculated that the variability in this
      technique would contribute about 21 additional subjects to overall sample size
      estimates in studies comparing the mean areas of cortical opacities. In many
      studies this would be a small addition to total sample size requirements. This
      technique provides clinically useful measurements of the size of a cortical
      opacity as seen on a retroillumination photograph. This may be useful for future
      clinical studies on natural progression of cortical cataracts as well as for
      clinical trials of anticataract drugs.

PMID- 7720403
TI  - Proteolysis by calpain is an underlying mechanism for formation of sugar cataract
      in rat lens.
AB  - To confirm the effect of a new aldose reductase inhibitor (ARI), rat lenses were
      cultured with xylose. ARI prevented opacities and reduced lens hydration caused
      by xylose. Next, cataract was produced by feeding a diet containing 50%
      galactose. ARI was tested for amelioration of cataract. On day 19 after feeding
      of galactose, nuclear cataracts were visible in 75% of the animals receiving only
      galactose, while nuclear cataracts were not observed in animals treated with ARI.
      In galactose cataract, lens hydration and calcium were significantly increased.
      Calpain in soluble and insoluble fractions was decreased. Alpha- and beta
      crystallins were proteolyzed. These changes were inhibited by administration of
      ARI. These results suggested that proteolysis by calpain is an underlying
      mechanism in formation of sugar cataract in rat lens.

PMID- 7720404
TI  - Thrombin induced cytoskeletal change in cultured bovine corneal endothelial cells
      mediated via protein kinase C pathway.
AB  - We studied the participation of the protein kinase C pathway in thrombin-induced
      cytoskeletal alterations in confluent cultured bovine corneal endothelial (BCE)
      cells. Cultured BCE cells were exposed to alpha-thrombin (0.1-10 U/ml for 15-60
      min) and the distribution of F-actin and vinculin plaques was examined using
      immunofluorescent staining and electron microscopy. Phorbol 12-myristate 13
      acetate (PMA, 10 nM for 15 min), the broad spectrum protein kinase inhibitors
      staurosporine (10 nM) and H-7 (10 nM), and highly specific PKC inhibitor
      calphostin C (10 nM) were used to evaluate the role of PKC/phosphorylation in
      this phenomenon. HA-1004 (10 nM) was used as a negative control for these
      inhibitors. In a parallel experiment, PKC activity of cytosol and membrane of BCE
      cells was also evaluated. In control samples, F-actin was distributed mainly at
      the periphery of cells, where it formed dense peripheral bundles; vinculin
      plaques were also present at the cell boundary. Exposure of BCE cells to thrombin
      changed the distribution of F-actin and vinculin into a diffuse pattern; a
      similar alteration was also induced by incubation with PMA. These phenomena were
      blocked by incubation with H-7, staurosporine and calphostin C. Both cytosolic
      and membrane PKC activity was increased after 5 to 30 min exposure of alpha
      thrombin and returned to the control level after 1 h. alpha-Thrombin induces
      alteration in the cytoskeleton of BCE cells, and this message is transduced at
      least in part by PKC dependent pathways. PKC/phosphorylation may thus play an
      important role in physiological processes that involve alterations of the
      cytoskeleton.

PMID- 7720405
TI  - Involvement of LFA-1 and ICAM-1 in the herpetic disease resulting from HSV-1
      corneal infection.
AB  - Herpes simplex virus type 1 (HSV-1) corneal infection in immunologically normal
      mice results in a transient epithelial lesion followed in about 2 weeks by a
      potentially blinding inflammatory response in the corneal stroma, and a mild
      blepharitis. Similarly infected T cell-deficient mice do not develop corneal
      stromal inflammation, but exhibit severe periocular skin disease and succumb to
      viral encephalitis. The role of certain adhesion molecules in both T cell
      activation, and in the extravasation of inflammatory cells from the blood into
      inflammatory sites is now being established. These studies investigated the
      involvement of the adhesion pair LFA-1/ICAM-1 in the disease that results from
      HSV-1 corneal infection in mice. Treatment of mice with mAb to LFA-1 beginning 1
      day before HSV-1 corneal infection resulted in a delay in the onset of stromal
      inflammation, but ultimately stromal inflammation developed to a normal extent.
      This treatment also caused a significant exacerbation of periocular skin disease,
      but did not render mice susceptible to encephalitis. Treatment with mAb to ICAM-1
      beginning 1 day before HSV-1 corneal infection caused an acceleration of both
      stromal inflammation and periocular skin disease, and rendered mice uniformly
      susceptible to lethal encephalitis. Treatment with either mAb beginning 6 days
      after HSV-1 corneal infection did not significantly affect the clinical course of
      herpetic disease. Our findings suggest that LFA-1 may play a role in the early
      phase of corneal stromal inflammation following HSV-1 corneal infection. Both LFA
      1 and ICAM-1 appear to be important for protection of the skin from HSV-1
      infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720406
TI  - Optimal conditions required for the creation of an iatrogenic chorioretinal
      venous anastomosis in the dog using argon green laser photocoagulation.
AB  - We have previously reported iatrogenic retinal to choroidal vein anastomosis,
      developed as a potential method of by-passing the site of obstruction to venous
      outflow in retinal venous occlusion in dogs (1), and in rats (2). In order to
      minimise tissue damage to the retina and choroid and increase the rate of success
      in these experiments, we investigated in the dog model the factors that would
      promote an anastomosis and compare the effects of three different power levels. A
      small spot size (50 microns) argon green laser beam of 514 nm at power levels of
      0.5w, 1.5w and 2.5w were used. Spaced serial sections from each lesion were
      examined by light and by transmission electron microscopy. Morphometric
      measurements of the corresponding retinal pigment epithelium (RPE)/glial scar was
      computed using IBMPC digitising pad and sigma scan software and the extent of
      tissue damage at the different power levels assessed. At the lowest power level
      of 0.5w the damage to the retina was mild and there was an absence of anastomosis
      formation. At the 1.5w power level an anastomosis formed in 40% of the lesions.
      At the highest power level of 2.5w a 71% rate of success was obtained however,
      the damage to the retina tended to be severe. The results of this study also
      indicate that disruption of Bruch's membrane and vein rupture at the time of
      irradiation are essential for anastomosis formation, which may be further
      enhanced by necrotic tissue, retinal pigment epithelial and glial scar formation
      and inflammation. These findings are useful in establishing optimal conditions
      for the creation of a chorioretinal venous anastomosis, for consideration in
      human trials.

PMID- 7720407
TI  - The role of the lens epithelium in development of UV cataract.
AB  - In view of renewed interest in the lens epithelium as the initiation site for
      cataract development, it seemed timely to review recent studies which appear to
      establish UV damage in the lens epithelium as the cause of UV cataract. While UV
      photons can and do interact with lens proteins in the cortex and nucleus,
      experimental results from cultured lenses and tissue cultured epithelial cells
      also demonstrate both mutagenic and cytotoxic effects in the epithelium. This
      minireview examines UV-induced changes in lens physiology that appear to follow
      epithelial cell damage, including inactivation of critical enzymes of transport
      and metabolic processes. Changes in membrane function include altered cation
      transport, increased permeability, and altered biosynthesis. One potential
      scenario for the propagation of damage from the epithelium to the underlying
      fiber cells includes calcium elevation, an early event in cataract development
      and critical to many physiological processes.

PMID- 7720408
TI  - Disability and the transition to adulthood: issues for the disabled child, the
      family, and the pediatrician.
AB  - The pediatrician treating a child with a disability must focus not only on the
      physical needs of the child but also on the emotional and social issues
      associated with being disabled in our society. This dual focus becomes
      increasingly important as the child matures through adolescence and transitions
      into adulthood. In addition, the pediatrician must understand the complex
      interrelationships between the family and their maturing, disabled child during
      the vital process of separation from the family. This transition is particularly
      difficult for an adolescent who is dependent on others for physical care and
      other independent living skills. Many of the transitional problems faced by
      disabled adolescents and their parents have roots in early childhood. With an
      awareness of the specific stressors on the parent caregivers and an understanding
      of the influence of disability on the developmental processes, the pediatrician
      can play a major role in easing the transition of a disabled adolescent into
      adulthood. By guiding the parents of a young child through the important tasks of
      childhood and adolescence, the pediatrician can set the stage for both the
      parents and their disabled child to have independent, yet supportive lives--lives
      that are focused not on the disability but on mutual respect and life
      satisfaction. It is recommended that disabled teens and young adults be given
      more help in independence skills, personal counseling services should be made
      available, and physicians should give teens age-appropriate information about
      disabilities. There are needs for sex education, preparation for parenthood, and
      genetic counseling. Other issues that should be addressed are early vocational
      awareness, alternatives to work, and leisure time use. Just because an adolescent
      is disabled, we cannot assume that he or she will have self-esteem and self
      concept difficulties. To adjust to being devalued by society, the disabled person
      must challenge societal beliefs that strength, independence, and appearance are
      the essential aspects of a quality life. The importance of being kind,
      intelligent, and productive to one's capacity must become more important. (See
      Table 3 for additional resource information.)

PMID- 7720409
TI  - Impact of maternal employment on the health of the family.

PMID- 7720410
TI  - Histone acetylation: facts and questions.
AB  - The DNA of eukaryotic cells is organized in a complex with proteins, either as
      interphase chromatin or mitotic chromosomes. Nucleosomes, the structural subunits
      of chromatin, have long been considered as static structures, incompatible with
      processes occurring in chromatin. During the past few years it has become evident
      that the histone part of the nucleosome has important regulatory functions. Some
      of these functions are mediated by the N-terminal core histone domains which
      contain sites for posttranslational modifications, among them lysine residues for
      reversible acetylation. Recent results indicate that acetylation and
      deacetylation of N-terminal lysines of nucleosomal core histones represent a
      means of molecular communication between chromatin and the cellular signal
      transduction network, resulting in heritable epigenetic information. Data on
      enzymes involved in acetylation and the pattern of acetylated lysine sites on
      chromosomes, as well as genetic data on yeast transcriptional repression, suggest
      that acetylation may lead to structural transitions as well as specific
      signalling within distinct chromatin domains.

PMID- 7720411
TI  - Methylation imprinting was observed of mouse mo-2 macrosatellite on the
      pseudoautosomal region but not on chromosome 9.
AB  - Mouse mo-2 macrosatellites consisting of 31-bp tandem repeat units are mainly
      located at two loci in the C57BL/6 genome, one being at the centromere-distal
      telomeric region of chromosome 9 and the other at the pseudoautosomal (PA) region
      of chromosomes X and Y. The two clusters constitute approximately 300 kb and 150
      kb, respectively. Southern analysis of a methylation-sensitive enzyme, HpaII
      digested DNA showed that the mo-2 macrosatellites are detected as more than 30
      polymorphic bands. Comparison of those bands between reciprocally crossed F1 mice
      revealed that approximately 20% of the allele-specific fragments exhibit
      different band intensities depending on the sex of the parent of origin. The
      differential methylation is observed in the mo-2 macrosatellite on the PA region
      but not in that on chromosome 9. Several fragments including the 3.4-kb fragment
      without internal HpaII site are more clearly detected when paternally derived,
      suggesting that the male-derived macrosatellite is undermethylated.
      Interestingly, the difference is much more remarkable in inter-subspecific F1
      mice between C57BL/6 and MSM than F1 between C57BL/6 and C3H/He. This suggests
      the presence of a modifier(s) that affect(s) the methylation of mo-2 in the MSM
      genome.

PMID- 7720412
TI  - Analysis of centromeric activity in Robertsonian translocations: implications for
      a functional acrocentric hierarchy.
AB  - Approximately 90% of human Robertsonian translocations occur between
      nonhomologous acrocentric chromosomes, producing dicentric elements which are
      stable in meiosis and mitosis, implying that one centromere is functionally
      inactivated or suppressed. To determine if this suppression is random,
      centromeric activity in 48 human dicentric Robertsonian translocations was
      assigned by assessment of the primary constrictions using dual color fluorescence
      in situ hybridization (FISH). Preferential activity/constriction of one
      centromere was observed in all except three different rearrangements. The
      activity is meiotically stable since intrafamilial consistency of a
      preferentially active centromere existed in members of six families. These
      results support evidence for nonrandom centromeric activity in humans and, more
      importantly, suggest a functional hierarchy in Robertsonian translocations with
      the chromosome 14 centromere most often active and the chromosome 15 centromere
      least often active.

PMID- 7720413
TI  - RFLP analysis of chromosomal fragments in genetic mosaic strains of Bombyx mori.
AB  - Mottled striped (pSm), a genetic mosaic strain for larval body marking of the
      silkworm, Bombyx mori, contains a small chromosomal fragment generated by
      breakage near the end of the 2nd chromosome. This fragment carries the striped
      marking (pS) gene and part of the chorion gene clusters. To determine the
      structural features of this fragmented chromosome, we studied the organization of
      the chorion genes on the fragment using restriction fragment length polymorphism
      (RFLP) analysis. Two of three classes of chorion gene family probes detected
      RFLPs in the two phenotypes, pSm (p/p/pS), and p (p/p), which had lost the
      fragment, segregated among the siblings of a mottled striped strain. Although
      hybridization patterns were basically identical between them, one or two
      additional bands were always observed associating with the mosaic phenotype
      (pSm). This suggests that the additional bands correspond to extra copies of
      chorion genes on the chromosomal fragment, which have a different structure from
      ones on the intrinsic 2nd chromosomes. Such heterogeneity of chorion genes may
      have been maintained since the beginning of mosaic induction, due to the absence
      of recombinational events between the two chromosomes. We are unable to detect
      any RFLPs by hybridization with the early class of chorion genes, implying that
      chromosomal breakage might have occurred between the two chorion clusters, Chl-2
      and Ch3, which are located approximately 4 cM apart from each other. Based on
      RFLP analyses for two independent mosaic strains (788 and 872), we postulate a
      common chromosomal origin with independent breakpoints and construct structural
      models for the two kinds of chromosomal fragments.

PMID- 7720414
TI  - Localization of antigens PwA33 and La on lampbrush chromosomes and on
      nucleoplasmic structures in the oocyte of the urodele Pleurodeles waltl: light
      and electron microscopic immunocytochemical studies.
AB  - Monoclonal antibodies A33/22 and La11G7 have been used to study the distribution
      of the corresponding antigens, PwA33 and La, on the lampbrush chromosome loops
      and nucleoplasmic structures of P. waltl oocytes, using immunofluorescence,
      confocal laser scanning microscopy and immunogold labeling. The results obtained
      with these antibodies have been compared with those obtained with the Sm-antigen
      specific monoclonal antibody Y12. All these monoclonal antibodies (mAbs) labeled
      the matrices of the majority of normal loops along their whole length.
      Nucleoplasmic RNP granules showed a strong staining with the mAbs La11G7 and Y12
      throughout their mass, but with the mAb A33/22, they showed only a weak
      peripheral labeling in the form of patches on their surface. This patchy labeling
      was confirmed by confocal laser scanning microscopy. Electron microscopy revealed
      that this patchy labeling might be due to a hitherto undescribed type of
      submicroscopic granular structure, around 100 nm in either dimension, formed by
      10-nm particles. Such granules were observed either attached to the RNP granules
      or free in the nucleoplasm, but rarely in relation with the normal loop matrices.
      These 100-nm granules may have a role in the movement of proteins and snRNPs
      inside the oocyte nuclei for storage, recycling, and/or degradation. Our results
      also suggest that all the microscopically visible free RNP granules of the
      nucleoplasm of P. waltl oocytes correspond to B snurposomes. The granules forming
      the B (globular) loops showed a labeling pattern similar to that of B
      snurposomes; their possible relationship is discussed.

PMID- 7720415
TI  - Identification and sequence characterization of a 1.3 Kb EcoRI repeat fragment
      that harbors a DNA repair site of rat pachytene spermatocytes.
AB  - Introduction of well-programmed nicks and gaps and the associated DNA repair
      activity in the genome at the pachytene interval is a characteristic feature of
      the meiotic prophase in organisms as varied as lilium and mouse. In the present
      study we have shown that the DNA synthetic activity in rat pachytene
      spermatocytes is insensitive to aphidicolin, a specific inhibitor of DNA
      polymerase alpha, delta and epsilon, suggesting DNA beta-polymerase-mediated
      repair synthesis in these cells. We have developed a novel approach for the
      isolation of the DNA repair sites by combining two independent techniques.
      Following incorporation of BrdUrd into pachytene spermatocytes in the presence of
      aphidicolin, the repair sites were released as ssDNA fragments by treatment of
      nuclei with 30 mM NaOH. Subsequently, the BrdUrd containing ssDNA fragments were
      specifically isolated using polyclonal anti-BrdUrd antibodies. The DNA fragments
      released were of two size classes, namely 4-7S (major) and 9-12S (minor) and
      constituted approximately 1.75% of the pachytene genomic DNA. These DNA repair
      fragments were distinct from Okazaki fragments and other replicative
      intermediates isolated from rat bone marrow cells as evidenced by (a) their
      different size distribution and (b) little cross-hybridization. Southern
      hybridization of restriction enzyme digests of rat genomic DNA with probes made
      against BrdUrd-ssDNA fragments revealed that although the repair sites were
      distributed throughout the genome, strong hybridization signals were observed in
      EcoRI. (1.3 kb and 2.4 kb), BamH1 (9 kb) and HindIII (5 kb) repetetive DNA
      fragments. The EcoRI 1.3 kb family were cloned into M13 mp19, and a repair
      positive (1.3 A) and a repair negative (1.3 B) were identified and sequenced. The
      repair positive clone contained (a) (CA)22 repeat, (b) a (CAGA)6 repeat and (c) 4
      sequences sharing high homology with various hypervariable minisatellite (HVMS)
      sequences. One of the HVMS sequence contained a GGCAGG motif known to be
      responsible for germline instability. The repair negative clone had (a) (CA)6
      repeat and (b) a HVMS like sequence without GGCAGG. The significance of these
      motifs and their relevance to the events of DNA metabolism at pachytene interval
      have been discussed.

PMID- 7720416
TI  - The karyotype of Alligator mississippiensis, and chromosomal mapping of the ZFY/X
      homologue, Zfc.
AB  - Comparative mapping studies of X-linked genes in mammals have provided insights
      into the evolution of the X chromosome. Many reptiles including the American
      alligator, Alligator mississippiensis, do not appear to possess heteromorphic sex
      chromosomes, and sex is determined by the incubation temperature of the egg
      during embryonic development. Mapping of homologues of mammalian X-linked genes
      in reptiles could lead to a greater understanding of the evolution of vertebrate
      sex chromosomes. One of the genes used in the mammalian mapping studies was ZFX,
      an X-linked copy of the human ZFY gene which was originally isolated as a
      candidate for the mammalian testis-determining factor (TDF). ZFX is X-linked in
      eutherians, but maps to two autosomal locations in marsupials and monotremes,
      close to other genes associated with the eutherian X. The alligator homologue of
      the ZFY/ZFX genes, Zfc, has been isolated and described previously. A detailed
      karyotype of A. mississippiensis is presented, together with chromosomal in situ
      hybridisation data localising the Zfc gene to chromosome 3. Further chromosomal
      mapping studies using eutherian X-linked genes may reveal conserved chromosomal
      regions in the alligator that have become part of the eutherian X chromosome
      during evolution.

PMID- 7720417
TI  - [Experimental study on mechanism of steroid-induced avascular necrosis of femoral
      head].
AB  - The authors adopted an animal model to observe the pathogenic mechanism of
      steroid-induced avascular necrosis of the femoral head. Sixty-four white rabbits
      were divided into two groups: hydrocortisone acetate (8 mg/kg) was hypodermically
      given to 48 experimental animals and 0.32 mg/kg of normal saline to 16 rabbits
      for control. Two groups of animals were fed and kept in the same condition. The
      results showed that application of the steroid drug could produce fat
      degeneration and necrosis of osteocytes and fat embolism in the small blood
      vessels of the femoral head. The abnormal hypertrophied fat cells in the bone
      marrow compressed small veins in the femoral head resulting in blood stasis of
      the capillaries, thus growth and regeneration of the capillary were inhibited.

PMID- 7720418
TI  - [Clinical and pathological changes of ischemic necrosis of the femoral head in
      children].
AB  - A total of 54 cases (73 hips) with ischemic necrosis of the femoral head after
      treatment of CDH have been followed up with an average of 7 years. We found that
      89% cases of type I and 70% of type II recovered to normal and 83% cases of type
      III and IV developed the coxa breva deformity due to injury of longitudinal
      growth plate of the proximal end of the femur. According to the value of ATD, the
      coxa breva was divided into three types. The L shape growth disturbance line
      revealed by X-ray is considered as a marker for determination of early epiphyseal
      plate injury by the authors.

PMID- 7720419
TI  - [Prediction of segmental collapse of femoral head after femoral neck fracture by
      scintimetry].
AB  - A follow-up study regarding the occurrence of segmental collapse of femoral head
      has been done in 53 patients of united femoral neck fracture including a periodic
      examination by 99mTc-MDP scintimetry. The results showed that the sequential
      variations in the nuclide uptake ratio of the femoral heads could reflect the
      histological repairing process and metabolic level in the femoral head. A
      sustainedly high nuclide uptake in 12 months after operation often denotes that
      there are defects in the repairing process of the ischemic femoral head, and that
      the segmental collapse of the femoral head will ensue.

PMID- 7720420
TI  - [Diagnostic value of MRI in non-traumatic osteonecrosis of femoral head at early
      stage].
AB  - To determine whether magnetic resonance imaging (MRI) can demonstrate the early
      stage changes of avascular necrosis of the femoral head that are not detectable
      radiographically. Clinical examinations, radiography and MRI were performed in
      twenty-six patients (thirty hips) at high risk. On the basis of the pathological
      findings of core biopsies, the results demonstrate that MRI had an accuracy of
      96.7% in diagnosing pre-radiologic stage necrosis of the femoral head in this
      series.

PMID- 7720421
TI  - [A newly designed multifunctional intramedullary decompressor and its clinical
      application].
AB  - A newly designed multifunctional intramedullary decompressor has been introduced
      in this paper. It has the following functions: (1) intramedullary decompression
      of femoral head; (2) curettage of necrotic bone; (3) biopsying (4) taking out
      iliac bone and placing bone graft; (5) taking out broken snail. Thirty four cases
      of 46 avascular necrotic femoral heads have been treated by using this
      decompressor, all cases had satisfactory results 18 weeks after operation.

PMID- 7720422
TI  - [MRI in the diagnosis of avascular necrosis of the femoral head].

PMID- 7720423
TI  - [Total hip arthroplasties in 190 cases: follow-up study].
AB  - One hundred and ninety-six cemented total hip arthroplasties performed in 190
      patients (mean age, 62 years) followed-up with an average of 8.7 years were
      reviewed. The results were compared with the same group previously reported at an
      average follow-up of 4 years. Clinically satisfactory results were observed at
      the short- and medium-terms. Evaluation of the study with Harris score system
      showed that the score records fell from 85 to 78.4 points in the same group and
      the revision rate rose from 6.84% to 14.73%. The main causes of the prosthesis
      failure were loosening of the prosthesis and of breakage of the prosthesis stem.
      This follow-up study showed that the short-term prosthesis failure was mainly
      related to the cement-fixing technique, while the medium-term failure was due to
      side effects of the cement. This series showed that cemented prosthesis is a good
      selection especially for elderly patients.

PMID- 7720424
TI  - [Comparative study of three different hip function evaluation systems].
AB  - Harris's, Charnley's and Beijing's numerical rating systems were used to evaluate
      the functional results of 42 cases of bipolar type artificial femoral head
      replacement. The results of assessment of the three methods were compared
      statistically and proved that the results are comparable. Before the overall
      evaluation, the patients should be divided into three groups (according to
      Charnley's method) on the basis of their original capacity of locomotion. The
      score results of the three groups should not be mixed up. The calculation method
      of total score of Beijing system may need certain modification. The advantages
      and disadvantages of the three systems, the significance of capacity assessment
      of daily activity and radiological evaluation are discussed on the basis of the
      results of analysis.

PMID- 7720425
TI  - [Bony changes at the femur side after hip joint replacement: radiologic analysis
      of 80 hip joints].
AB  - The authors, according to Amstutz, studied the roentgenographs of 80
      postoperation cases of cemented hip joint replacement performed more than two
      years-ago. There were bone changes in 64 cases (80%), of them, sclerosis of bone
      in 32 cases (40%), atrophy of bone in 25 cases (31%), absorption of bone in 24
      cases (30%), thickness of bone cortex in 18 cases (22%), enlargement of medullary
      cavity in 12 cases (15%), periosteum reaction in 8 cases (10%), and thinness of
      bone cortex in 1 case (1.3%). Most of them usually occurred in the sixth month to
      the second year post-operation and located mainly at the 1, 4, 5 and 7 regions.
      The authors think that the most important cause is the unbalance of biologic
      stress, and other factors are elasticity and hardness of prosthesis, frictional
      force, cemented of the stem, etc.

PMID- 7720426
TI  - [Follow-up result of 14 cases of the first metatarsophalangeal joint arthroplasty
      with titanium total joint prostheses].
AB  - An 8-year follow-up study of 14 cases (22 feet) of titanium total 1st
      metatarsophalangeal joint arthroplasty with two designs (type I and type II) is
      reported. The follow-up period average was 5 years with a range of 3 to 8 years.
      The rate of subjective satisfaction was 72.7% (16/22), the incidence of
      complications 31.8% (7/22), and the rate of revision 27.3% (6/22). The results
      implicate that titanium total hallux MTP joint arthroplasty is a suitable
      procedure for osteoarthritis, rheumatoid arthritis and hallux rigidus of the 1st
      MTP joint, and that type II prosthesis seems better than type I prosthesis. In
      addition, prosthetic designing, surgical technique and postoperative
      complications are also discussed in detail.

PMID- 7720427
TI  - [Tricuspid valve re-replacement: analysis of 4 cases].
AB  - The patients underwent tricuspid valve replacement may occur the mechanical valve
      failure caused by thrombosis and so on. It is necessary to reoperate urgently
      otherwise the patients will die. Four patients with this complications were
      treated successfully with tricuspid valve re-replacement at Fuwai Hospital in
      Beijing, China since 1989. The experience of management, the technique of
      tricuspid valve re-replacement and the choice of the valves were discussed.

PMID- 7720428
TI  - [Mitral valve replacement with preservation of papillary muscles and chordae
      tendineae: a report of 53 cases].
AB  - Mitral valve replacement with preservation of papillary muscles and chordae
      tendineae (MVRP) was carried out in 53 cases in this group, among whom 17
      underwent combined mitral and aortic valve replacement (AVR), 36 underwent simple
      mitral valve replacement (MVR) and tricuspid valve plasty was performed in 28
      cases simultaneously. All the patients were given echocardiography one and six
      months after operation respectively which showed: (1) The left ventrical function
      of this group was obviously superior to that of the conventional mitral valve
      replacement (MVRC) group in the same period (SVI, EF, FS, P < 0.05) (2) The open
      shut velocity of the prosthetic disc was quicker (3) The contradictory movement
      of the ventrical septum disappeared. The follow-up for 2 to 36 months showed that
      all the patients were alive and healthy. It is suggested that MVRP can facilitate
      better recovery of the left ventrical function than MVRC and long-term results
      are excellent.

PMID- 7720429
TI  - [Resections of tracheal or bronchial tumors and tracheal or bronchoplasty:
      experience with 53 patients].
AB  - From January 1982 to December 1992, a total of 485 patients with pulmonary tumors
      were treated by surgical procedure, in which 53 cases (92.4%) were treated by
      segmental resections of trachea, carina, bronchi and with tracheal-or
      bronchoplasty. In this series of tracheal-or bronchial tumors, four (7.6%) were
      benign, 49 (92.4%) were malignant. Segmental resections of trachea and carina
      with plastic procedures were performed on 6 cases, sleeve resections of main
      bronchi with plastic procedures were performed on 47 cases. One case (1.9%) died
      of respiratory failure postoperatively. FOLLOW-UP: the survival rate of 5 years
      was 35% (6/17), three years' was 56% (18/32), one year's was 77.8 (35/45). We
      considered that the patients with tumors of trachea or bronchi had significant
      symptom-irritated cough with bloody sputum. Earlier diagnosis, earlier surgical
      treatment could get a better therapeutic result. Segmental resections of trachea
      and sleeve resections of bronchi with lobectomy extended the indications for
      treating pulmonary neoplasm, and saved the normal lung tissues and functions as
      more as possible, provided some operative chances for elder patients and those
      cases with insufficient pulmonary functions. This procedure improved the
      patients's life quality and left the possibility of reoperation.

PMID- 7720430
TI  - [Thoracic gastric and large area necrotic perforation of the neck gastric wall
      after surgery of esophageal and cardial cancer: analysis of 9 cases].
AB  - Nine cases of gastric perforation after operation for esophageal were reported.
      Eight cases were esophageal cancer. One case was cardial cancer. Five of the nine
      cases were anastomosed in intrathorax, and four in neck. Intrathoracic gastric
      perforation occurred in six cases. Five of them were operated on again. Gastric
      perforation in neck occurred in three cases. The nine cases were all cured. This
      article analysed the reasons of the gastric perforation and emphasised that early
      diagnosis, early operation or drainage in neck were the key steps in treatment.

PMID- 7720431
TI  - [Self-made fibrin sealant administered in thoracic surgery].
AB  - From April 1990 to May 1993, 15 patients with thoracic complication or thoracic
      diseases have been treated with self-made fibrin sealant. All patients have been
      cured successfully in a short time without thoracotomy. The methods of its make
      up, administer and assessment were discussed. It is economical and effective. The
      major advantage is simple method and easily administered. It could be used in
      other surgery.

PMID- 7720432
TI  - [Interventional therapy of hepatic cavernous hemangioma].
AB  - From March. 1991 through Dec. 1993, 39 patients with hepatic cavernous hemangioma
      were treated by interventional therapy. After 1-3 periods of therapy 28 were
      cured, in 8 case the mass reduced by 50%, and in the remaining 3 cases the tumor
      reduced by 30%. Symptoms disappeared in all patients. The diagnosis of hepatic
      cavernous hemangioma, its differential diagnosis from malignant tumors,
      indications for interventional therapy, the use of embolizing materials were
      discussed.

PMID- 7720433
TI  - [Glucagonoma syndrome report of one case and review of the chinese literature].
AB  - This paper reports one case with glucagonoma syndrome that resection of the
      primary glucagonoma in the pancreas was done. There was metastasis one in liver
      and lymph node. The definitive diagnosis was established by immunohistochemical
      analysis. The patient by immunohistochemical analysis. The patient remained well
      for 27 months and gained 5 kg of weight. Another experiences of diagnosis and
      treatment of 8 cases of malignant glucagonoma collected in chinese literature
      were reviewed. The clinical specialty of glucagonoma syndrome. diagnosis and
      management were discussed suggesting two points: on diagnosis the clinical
      specialty is a important clues: palliative primary tumor resection may be
      significant clinical improvement and prolonged survival.

PMID- 7720434
TI  - [Application of microsurgical technique in the intrasinus renalis
      pyeloureteroplasty in pelvic atresia in children].
AB  - Seven cases of pelvic atresia in children were treated by the intrasinus renalis
      pyeloureteroplasty with the application of microsurgical technique. The site of
      pelviureteric anastomosis was unobstructed and the hydronephrosis was greatly
      improved through postoperative examinations of intravenous urography and
      renogram. This procedure provides clear field, simple performance and high
      successful rate. The prevention of complete pelviureteric laceration and pelvic
      atresia in children, the advantages of the microsurgical technique, and the
      operation precautions are discussed.

PMID- 7720435
TI  - [The changes in retinol-binding protein, N-acetyl-beta-glucosaminidase, albumin
      and IgG in urine before and after ESWL].
AB  - The retinol-binding protein (RBP), N-acetyl-beta-glucosaminidase, (NAG) albumin
      (alb) and IgG in urine were measured from 67 patients with urinary stone before
      and after ESWL. The results showed that the amount of alb, IgG and RBP in urine
      was obviously increased for the patients with renal, upper ureteral or lower
      ureteral stone associated with hydronephrosis. ESWL may injure the glomerule and
      tubules by direct or indirect action. 2 weeks after ESWL, the alb, IgG and RBP in
      urine returned to normal in 56.8%, 70.3% and 51.4% of cases respectively.
      Therefore we suggest that retreatment should be put off as late as 2 weeks after
      the first ESWL. However, it is not limited for retreatment of lower ureteral
      stones without hydro nephrosis.

PMID- 7720436
TI  - [Hyperdynamic status in a partial portal vein ligated (PVL) rat's portal
      hypertension model].
AB  - The splanchnic and systemic hemodynamics were measured by radioactive microsphere
      techniques in a PVL rat's model with portal hypertension. The portal-hypertensive
      rats (1.75 +/- 0.24 vs. 1.23 +/- 0.13 kPa, P < 0.001) with greater than 93%
      portal-systemic shunting had an increase in portal venous inflow by 50% (8.97 +/-
      0.8 vs. 6.03 +/- 0.28 ml.min-1.100gBW-1; P < 0.001) and a concomitant decrease by
      40% in splanchnic arteriolar resistance (0.27 +/- 0.05 vs. 0.42 +/- 0.05kPa.ml
      1.min-1.100gBW-1; P < 0.01) compared with control rats. Cardiac index (54.6 +/-
      4.4 vs. 36.5 +/- 3.0 ml.min-1.100gBW-1) was elevated by 50% (P < 0.001), and
      total peripheral resistance (0.052 +/- 0.006 vs. 0.084 +/- 0.009 kPa.ml-1.min
      1.100gBW-1) was decreased by 40% (P < 0.001). The resistance to portal blood flow
      in portal vein-stenotic rats (0.087 +/- 0.011kPa.ml-1.min-1) was similar to that
      in control rats (0.076 +/- 0.01kPa.ml-1.min-1), indicating that the hyperdynamic
      portal venous inflow, not resistance, was the mainstay of the elevated portal
      venous pressure. Which is in favor of the forward flow theory of portal
      hypertension. The systemic hemodynamic parameters were secondary to the
      splanchnic hemodynamic changes.

PMID- 7720437
TI  - Prevalence of benign anorectal disease in a randomly selected population.
AB  - BACKGROUND: The prevalence of benign anorectal diseases (BAD) in the general
      population has been difficult to establish, either because the individual
      diseases themselves were difficult to characterize in surveys or because of bias
      in the selection of the survey population. Reported herein is a prevalence survey
      of BAD symptoms and treatment history of a sample of the general population,
      selected by random digit dialing. METHOD: A survey instrument that inquired into
      symptoms of BAD, BAD treatment history, and health-seeking behaviors was
      administered by telephone interview with 102 individuals, between the ages of 21
      and 65 of both genders and all races, chosen by random digit dialing in the
      Joliet, Illinois area. For selected variables (gender, education level, obesity,
      previous BAD treatment, fiber supplementation, time for defecation and reading
      during defecation all related to BAD symptoms) odds ratios and 95 percent
      confidence intervals were calculated. RESULTS: Of the 102 individuals, 9 had been
      previously treated for hemorrhoids, 4 by surgery, and 5 medically. Twenty
      individuals currently have BAD symptoms, six of these have multiple symptoms
      frequently, implying established BAD, and four of these have been previously
      treated for hemorrhoids. Seven of eight individuals with rectal bleeding in the
      past year have not sought medical evaluation. Of the associations tested,
      statistical significance was found only between female gender and BAD symptoms
      (odds ratio = 4.6; 95 percent confidence interval = 1.3-20.4). CONCLUSIONS:
      History of hemorrhoidal treatment and current BAD symptomatology are highly
      prevalent in a randomly selected population, and 80 percent of the subjects with
      symptoms of BAD have not consulted a physician regarding BAD. Some previously
      held correlates of hemorrhoidal symptoms, such as obesity and extended time for
      defecation, showed no apparent association with hemorrhoid treatment history or
      current BAD symptoms. The best predictors of current BAD symptoms were female
      gender (odds ratio = 4.6; 95 percent confidence interval = 1.3-20.4) and previous
      hemorrhoid treatment (odds ratio = 3.9; 95 percent confidence interval = 0.7-20).

PMID- 7720439
TI  - Severe Clostridium difficile colitis.
AB  - PURPOSE: Reports of fatality related to Clostridium difficile colitis and a sharp
      increase in prevalence of this infection prompted a study of patients who develop
      a more aggressive form of this disease. METHODS: Over 38 months, 710 patients at
      our institution developed C. difficile colitis. Twenty-one (3 percent) of these
      patients either required intensive care unit admission or died as a result of
      their infection. A retrospective, case-controlled study was undertaken to compare
      these patients, who were considered to have severe C. difficile colitis, with the
      remaining patients with milder disease. RESULTS: Factors that predisposed to the
      development of severe C. difficile colitis included intercurrent malignancy,
      chronic obstructive pulmonary disease, immunosuppressive and antiperistaltic
      medications, renal failure, and administration of clindamycin (P < 0.05 for all).
      Patients with severe C. difficile colitis were more likely to have abdominal
      pain, tenderness and distention, peritonitis, hemoconcentration (> 5 points),
      hypoalbuminemia (< 3 mg/dl), and elevated or suppressed white blood cell count (>
      25,000; < 1,500; P < 0.05 for all). These factors were used to create a scoring
      system that could distinguish between patients with severe C. difficile colitis
      and those with mild disease. Thirteen patients in the late stages of terminal
      illness with metastatic malignancy or age > 90 were considered poor or
      inappropriate surgical candidates. Only the remaining eight patients could have
      potentially recovered from operation with hope for long-term survival. Of these,
      seven were treated without colonic resection, and six of the seven survived,
      whereas one patient underwent colectomy and did not survive. CONCLUSIONS:
      Patients with severe C. difficile colitis can be readily identified. Often they
      have coexisting illness that precludes operation. In this series, only 1 of 21
      patients with severe C. difficile might have benefited from an aggressive
      surgical approach.

PMID- 7720438
TI  - Safety of urgent restorative proctocolectomy with ileal pouch-anal anastomosis
      for fulminant colitis.
AB  - PURPOSE: Subtotal colectomy with ileostomy is the operation of choice for
      patients with fulminant colitis. Restorative proctocolectomy (RPC) with ileal
      pouch-anal anastomosis (IPAA) is preferred for patients who undergo elective
      surgery for ulcerative colitis. We retrospectively evaluated the safety of RPC
      with IPAA in patients with a moderate form of fulminant colitis. METHODS: A chart
      review of 737 patients who underwent RPC with IPAA for ulcerative and
      indeterminate colitis from 1983 through 1992 was performed. Moderate fulminant
      colitis was defined as acute disease requiring hospitalization and parenteral
      steroid therapy, but without hypotension (systolic blood pressure, < 100 mmHg),
      tachycardia (> 120 beats/min), or megacolon. RESULTS: Twelve patients with
      moderate fulminant colitis underwent urgent surgery (1.6 percent). They had been
      treated preoperatively for 5.1 +/- 2.3 days with intravenous high-dose steroids,
      total parenteral nutrition, and antibiotics. These patients had a shorter length
      of disease (P = 0.01), lower hemoglobin, hematocrit, and albumin (P = 0.001), and
      higher temperature (P = 0.002) and leukocyte count (P = 0.007) than patients
      undergoing elective surgery. No early septic complications occurred, although
      perianal abscess occurred in one patient and pouch-anal fistula in another
      patient, 13 and 14 months after surgery, respectively. CONCLUSION: In carefully
      selected, hemodynamically stable patients with fulminant colitis and without
      megacolon, RPC with IPAA can be safely performed.

PMID- 7720440
TI  - Intraoperative ultrasonography in detection of hepatic metastases from colorectal
      cancer.
AB  - PURPOSE: This study was designed to compare diagnostic accuracies of measuring
      liver enzymes, preoperative ultrasonography, surgical examination, and
      intraoperative ultrasonography for detection of liver metastases from colorectal
      cancer. METHODS: Blind, prospective comparisons of diagnostic examinations
      mentioned above were performed in 295 consecutive patients with colorectal
      cancer. An experienced ultrasonologist performed the preoperative examinations,
      and results were unknown to the other experienced ultrasonologist who performed
      the intraoperative examinations. The latter, also was unaware of the findings by
      the surgeon. The presence of metastases was further assessed by ultrasonography
      three months postoperatively, as well as additional surgery and liver biopsy in
      some of the patients. RESULTS: The sensitivity of intraoperative ultrasonography
      (62/64) was significantly superior to that of surgical exploration (54/64) and
      that of preoperative ultrasonography (45/64). The lowest sensitivity was
      presented by liver enzymes. Bilobar metastases were detected in 42 of 46 patients
      by intraoperative ultrasonography but in only 33 patients by the surgeon.
      Intraoperative ultrasonography demonstrated the highest specificity of all
      examinations. CONCLUSIONS: Intraoperative ultrasonography reduces the number of
      patients with liver metastases from being subjected to superfluous or even
      harmful liver surgery, and it may increase the number in whom liver surgery will
      prolong life.

PMID- 7720441
TI  - Quality of life in colorectal cancer. Stoma vs. nonstoma patients.
AB  - PURPOSE: The bowel and sexual function of colorectal cancer patients undergoing
      either sphincter-saving or sphincter-sacrificing surgical procedures may be
      impaired. A legitimate question is how these different surgical techniques affect
      the patients' quality of life. METHODS: Seventeen studies were identified that
      compared at least one of four aspects of patient functioning (i.e., physical,
      psychologic, social, and sexual) between stoma patients and nonstoma patients.
      RESULTS: Although the literature does not yield entirely consistent findings,
      some long-term effects of surgery can be identified: 1) both patient groups are
      troubled by frequent or irregular bowel movements and diarrhea; 2) stoma patients
      report higher levels of psychologic distress than do nonstoma patients; 3)
      although both stoma patients and nonstoma patients report restrictions in their
      level of social functioning, such problems are more prevalent among patients with
      a colostomy; 4) sexual functioning of male and female stoma patients is
      consistently more impaired than that of male and female patients with intact
      sphincters. Results of the current review were compared with those of other,
      related areas. CONCLUSIONS: Although nonstoma patients generally fare better than
      do stoma patients, they also suffer from physical impairments induced by
      sphincter-saving procedures (e.g., impaired bowel and sexual function). These
      impairments may become more prevalent as ultralow anastomosis is more frequently
      applied, resulting in bowel and sexual dysfunction and related psychologic
      distress. Well-designed studies are needed that examine whether quality-of-life
      benefits are to be gained by use of ultralow anastomosis compared with colostomy.

PMID- 7720442
TI  - Relationship between manometric anal waves and fecal incontinence.
AB  - PURPOSE: The significance of manometric anal waves is uncertain, and their fate
      and diagnostic importance are unknown. It is conceivable that in neurogenic fecal
      incontinence (NFI) the frequency and amplitude of these waves may be altered into
      specific, recognizable patterns. Evaluation of this unexplored relationship
      between fecal incontinence and anal manometric waves has potential diagnostic
      use. METHODS: Anal motility was studied in 20 patients, each with NFI and
      traumatic fecal incontinence (TFI), and results were compared with findings in 20
      control subjects to determine changes in frequency and amplitude of anal waves in
      fecal incontinence. RESULTS: Frequency of slow waves when present (NFI =
      9.5/minute; TFI = 9.5/minute; control subjects = 9.1/minute) was identical in the
      three groups (P > 0.05). Amplitude of slow waves (NFI = mean, 4.3 mmHg; TFI =
      mean, 3.9 mmHg; control subjects = mean, 6.6 mmHg) was reduced in patients who
      were incontinent compared with control subjects but failed to reach statistical
      significance (P > 0.05). Frequency of ultraslow waves when present (NFI = mean,
      0.75/minute; TFI = mean, 0.6/minute; control subjects = mean, 1.2/minute) was not
      statistically different between the three groups (P > 0.05). Amplitude of
      ultraslow waves (NFI = mean, 10.5 mmHg; TFI = mean, 23.4 mmHg; control subjects =
      mean, 29.6 mmHg) was significantly reduced in NFI vs. control subjects (P < 0.01)
      and between TFI vs. control subjects (P < 0.05). CONCLUSIONS: Manometric slow and
      ultraslow waves, when present, retain their frequency characteristics,
      irrespective of underlying disease. Amplitude of slow waves was not statistically
      different from control subjects, but the amplitude of ultraslow waves was
      significantly decreased in patients who were incontinent.

PMID- 7720443
TI  - Coloanal anastomosis: are functional results better with a pouch?
AB  - PURPOSE: Different studies have shown that low colorectal and coloanal
      anastomosis often yield poor functional results. The aim of the present study was
      to investigate whether a colonic reservoir is able to improve functional results.
      METHODS: Thirty-eight consecutive patients subjected to low anterior resection
      were randomized following rectal excision in two groups. One (n = 19) had a
      stapled straight coloanal anastomosis, and the other (n = 19) had a 10-cm stapled
      colonic pouch low rectal anastomosis. Median anastomotic distance above the anal
      verge was 3.38 +/- 0.56 cm and 2.14 +/- 0.36 cm in both groups, respectively.
      Continence alterations, urgency, tenesmus, defecatory frequency, anal resting and
      maximum voluntary squeezing pressures, and maximum tolerable volume were
      evaluated one year later. RESULTS: One patient died of pulmonary embolism, and
      seven presented with a recurrence and were excluded from the study. Stool
      frequency was greater than three movements per day in 33.3 percent of cases with
      a reservoir and in 73.3 percent of those with a straight coloanal anastomosis (P
      < 0.05). Maximum tolerable volume was significantly greater in patients with a
      reservoir (335 +/- 195) than in those without (148 +/- 38) (P < 0.05). There were
      no significant differences in other variables studied. CONCLUSIONS: This study
      shows that some aspects of defecatory function after rectal excision could
      improve with a colonic reservoir.

PMID- 7720444
TI  - Anal fissure. 20-year experience.
AB  - PURPOSE: This study was designed to review a 20-year experience of the treatment
      of patients with anal fissure to identify possible etiologic factors and to
      explore effective preventative measures and the ideal treatment for this disease.
      METHODS: From January 1972 to December 1991, 1,391 patients (700 males, 691
      females; average age, 39 years) with chronic symptomatic anal fissures underwent
      surgical treatment using either open or closed techniques. The following
      procedures were performed: 1) internal sphincterotomy for 1,313 idiopathic
      fissures; 2) C-anoplasty for 36 cases of anal stricture; 3) debridement and
      sphincterotomy for 25 patients with postsurgical nonhealing wounds; 4) bilateral
      excision of the protruding internal sphincter for 17 patients with "subluxation."
      Acute superficial anal fissures were treated conservatively, with emphasis on
      anal hygiene. RESULTS: Acute superficial and fissures responded well to
      conservative management. Over 95 percent of patients with chronic anal fissures
      treated by surgery had satisfactory relief of symptoms. Early complications
      included urinary retention (1.4 percent), bleeding (1.1 percent), and abscess and
      fistula formation (0.7 percent). Late complications manifested as flatus and
      liquid incontinence (1.5 percent), delayed wound healing (1.4 percent),
      recurrence of fissures (1.3 percent), and symptomatic itching and burning (1.1
      percent). The complication rate was higher in the group that underwent closed
      sphincterotomy than in the group treated by open techniques. CONCLUSIONS: Proper
      and hygiene is important in both prevention and initial conservative management
      of symptomatic anal fissures. For chronic intractable cases, open lateral
      internal sphincterotomy is strongly recommended. C-anoplasty should be done when
      strictures are present. Excision of the protruding internal sphincter is
      recommended in patients who present with an excessively elongated, tight anal
      canal with a partially protruding internal sphincter.

PMID- 7720445
TI  - Endosonography of the anal sphincter after ileal pouch-anal anastomosis. Relation
      with anal manometry and fecal continence.
AB  - PURPOSE: The aim of the present study was to visualize supposed defects of the
      internal anal sphincter after ileal pouch-anal anastomosis (IPAA) by anal
      endosonography and to relate these findings with anal manometry and fecal
      continence. METHODS: We investigated 23 patients, visualized the sphincter
      complex by anal endosonography, and quantified the anatomic changes of the
      sphincter. Anal resting and squeezing pressures as well as length of the anal
      canal were determined by anal manometry. Continence was objectively scored by an
      observer not involved in treatment of patients and subjectively by patients
      themselves. RESULTS: At anal endosonography, the mean thickness of the internal
      anal sphincter was 1.16 mm (95 percent confidence interval, 0.98-1.33), which is
      significantly less than in normal volunteers. Tapering of the internal anal
      sphincter only occurred in six patients (of whom two had a gap in the internal
      sphincter). In 17 patients endosonography showed a thin internal anal sphincter
      without essential variation in thickness over the complete circumference.
      Approximately eight weeks after ileostomy closure following IPAA, maximum resting
      pressure (MRP) and length of the anal canal appeared to be significantly
      decreased compared with values before IPAA (P = 0.001 and 0.002, respectively).
      These differences were less striking (P = 0.05 and 0.04, respectively) when
      measured six or more months after ileostomy closure. The extent of reduction of
      the MRP and thickness of the internal anal sphincter were not correlated with
      grade of continence or with subjectively scored continence. CONCLUSIONS: IPAA
      leads to a reduction of thickness of the internal anal sphincter and reduction of
      the MRP. Tapering or gaps in the internal anal sphincter are probably caused by
      direct trauma to this sphincter because of mucosectomy, whereas in cases of
      circular reduction of thickness of the internal anal sphincter without tapering
      or gaps, direct trauma is an unlikely explanation; this reduction is probably
      caused by denervation. IPAA compromises continence to a variable degree in 18 of
      23 patients. No correlations were found between the extent of reduction of the
      MRP and the extent of reduction in internal anal sphincter thickness or between
      these two parameters and objectively or subjectively scored continence.
      Difficulties in obtaining reliable information on continence may be a causal
      factor. A striking discrepancy was noticed among objective, scored disturbances
      in continence, and overall satisfaction concerning level of continence by
      patients themselves.

PMID- 7720446
TI  - Twenty-year review of the surgical management of perianal Crohn's disease.
AB  - PURPOSE: A retrospective analysis of 48 patients treated over a 20-year period
      (March 1973-April 1993) was undertaken to assess the results of our practice of
      early surgical intervention in suppurative complications of perianal Crohn's
      disease. METHODS: All patients were either seen in the office within the last six
      months or contacted by phone. RESULTS: The average age of our patients was 30
      years at initial diagnosis. Thirty-four patients (71 percent) initially presented
      with intestinal disease and four (8 percent) with only perianal disease. Thirteen
      patients (27 percent) initially presented with simultaneous intestinal and
      perianal disease. The various fistulas at initial presentation included 8
      intersphincteric (17 percent), 14 transphincteric (29 percent), 11 complex or
      multiple (23 percent), 5 rectovaginal (10 percent), and 2 unclassified, for a
      total of 40 patients. Eight patients (17 percent) presented with only an abscess.
      Eighty five percent of our patients healed after their first procedure, with an
      average time to heal of 2.8 months. Thirteen (27 percent) patients had
      recurrences after initial healing of their wounds. The mean time to recurrence
      after healing was 5.25 years. Fifty-four percent of our recurrences (7 patients)
      were treated by incision and drainage of an abscess only. Seven of 13 recurrences
      healed after the second procedure (54 percent), and 5 of 6 healed after a third
      procedure (83 percent). Only seven (14 percent) of our patients underwent a
      proctocolectomy during the study period, through September, 1993. Our overall
      probability of avoiding proctectomy and healing perineal wounds of 86 percent is
      consistent with published literature. CONCLUSIONS: Early aggressive surgical
      management of suppurative complications of perianal Crohn's disease before
      complex management problems ensue results in a high incidence of healing and a
      low risk of subsequent proctectomy.

PMID- 7720447
TI  - Biofeedback for the treatment of fecal incontinence. Long-term clinical results.
AB  - Biofeedback therapy has been proposed as a treatment for fecal incontinence with
      good, short-term results. PURPOSE: This study was designed to assess long-term
      clinical results of biofeedback therapy compared with medical therapy alone and
      to assess manometric results in patients treated with biofeedback. METHODS: Two
      groups of incontinent patients were studied. Group 1 consisted of 16 patients (3
      males and 13 females; mean age, 59.9 years). Etiologies treated by biofeedback
      included descending perineum syndrome (7), postfistula or hemorroidectomy (4),
      and miscellaneous (5). Group 2 consisted of eight patients (two males, six
      females; mean age, 62.2 years). Etiologies treated with medical treatment alone
      (including enema and antidiarrheal therapy) included descending perineum syndrome
      (3), postfistula or hemorroidectomy (2), and miscellaneous (3). The incontinence
      score was initially 17.81 +/- 3.27 (standard deviation) in Group 1 and 17.0 +/-
      2.77 in Group 2. Resting pressure of the upper and lower anal sphincter, maximum
      squeezing pressure, and duration of contraction were not initially different in
      Groups 1 and 2 but were significantly lower than in the control group of patients
      without incontinence (n = 12; 8 males, 4 females; mean age, 66.4 years) (P <
      0.05). Follow-up duration was 30 months, with intermediate clinical score at 6
      months for Group 1. RESULTS: After biofeedback therapy, the incontinence score at
      30 months was lower in Group 1 (14.43 +/- 6.35 vs. 17.81 +/- 3.27; P < 0.035) and
      unchanged in Group 2 (18.0 +/- 2.72 vs. 17.0 +/- 2.77). However, in Group 1 the
      score at 6 months was much lower than at 30 months (6.31 +/- 7.81 vs. 14.43 +/-
      6.35; P < 0.001). Only the amplitude of voluntary contraction and upper anal
      pressure (51.1 (range, 27-90) vs 36.7 (range, 20-80) mmHg) were significantly
      increased (81.5 (range, 55-120) vs. 62.1 (range, 30-90) mmHg; P < 0.05).
      CONCLUSION: Biofeedback improved continence at 6 months and at 30 months.
      However, the score at 6 months was much better, suggesting that the initial good
      results may deteriorate over a long time. These data suggest that it could be
      useful to reinitiate biofeedback therapy in some patients.

PMID- 7720448
TI  - Primary suture of anorectal abscess. A randomized study comparing treatment with
      clindamycin vs. clindamycin and Gentacoll.
AB  - Gentacoll (Schering-Plough A/S, DK-3520 Farum, Denmark) implant is a biologically
      absorbable collagen with gentamicin, which enables local use of gentamicin in an
      abscess cavity. PURPOSE: To increase healing rate in treatment of perianal
      abscess with primary suture, the effect of intraoperative parenteral clindamycin
      and Gentacoll was investigated against monotherapy with intraoperative
      clindamycin in a randomized study. METHODS: One hundred seven patients, 55 in the
      Gentacoll group and 52 in the control group, were enrolled in the study and
      followed for three months. RESULTS: Twelve patients (22 percent) in the Gentacoll
      group developed a new abscess and/or fistula. In the control group nine patients
      (17 percent) developed a recurrent abscess or a fistula. In both groups 43
      patients had an uneventful course. The differences between the two groups were
      not significant. Of all 107 patients, 19.5 percent had recurrent disease in the
      follow-up period. Duration of hospitalization and reconvalescence were identical
      in both groups. One case of superficial thrombophlebitis was seen after
      clindamycin. No other adverse effects to either Gentacoll or clindamycin were
      seen. CONCLUSION: The study shows that Gentacoll is a safe preparation but is
      without value as a supplement to clindamycin in the treatment of acute perianal
      abscess with primary suture. The study has documented the value of this treatment
      under cover with a intraoperative dose of clindamycin.

PMID- 7720449
TI  - Confirmation of cecal intubation during colonoscopy.
AB  - PURPOSE: Establishing intubation of the cecum can be a laborious, frustrating,
      and sometimes erroneous endeavor. Following confirmed colonoscopic intubation of
      the cecum, the presence of three anatomic landmarks (alone and in combination)
      were evaluated to precisely define their reliability. METHODS: Between February
      1991 and January 1992, 771 of 904 consecutive colonoscopic examinations were
      completed to the cecum as confirmed by fluoroscopy. RESULTS: All three cecal
      landmarks studied (ileocecal valve, appendiceal orifice, and transillumination)
      were present in 64 percent of patients, and two landmarks were seen in 32 percent
      (96 percent of patients had multiple landmarks). The ileocecal valve was the most
      reliable cecal landmark (98 percent), followed by the appendiceal orifice (87
      percent) and transillumination through the abdominal wall (75 percent).
      CONCLUSIONS: The ileocecal valve is the most reliable cecal landmark and is
      invariably visualized, even when all other cecal landmarks are obscure. Although
      other cecal landmarks are usually identifiable, they are most valuable when found
      in association with the ileocecal valve.

PMID- 7720450
TI  - Abnormal internal anal sphincter fibrosis and elasticity in fecal incontinence.
AB  - PURPOSE: We aimed to investigate the changes in the proportion of collagen and in
      the elasticity of the internal anal sphincter in patients with neurogenic fecal
      incontinence. METHODS: Collagen content was studied in ten patients with
      neurogenic fecal incontinence (mean age, 51.5 years) and ten controls (age, 58.6
      years) using histologic techniques to determine differences between incontinence
      and health and to determine the effect of aging. Changes in elasticity were also
      measured in 8 controls (mean age, 63 years) and 13 patients with neurogenic
      incontinence (mean age, 60 years) by recording the in vitro length-tension
      relationship of the freshly excised internal anal sphincter. RESULTS: Incontinent
      patients had a significantly higher collagen content than controls (55 percent
      vs. 33 percent; P = 0.013). In incontinent patients the amount of collagen and
      the patients' ages correlated significantly (P = 0.001). There was a greater
      increase in stable tension per increase in muscle length in the strips from
      incontinent patients compared with controls. CONCLUSIONS: Changes in fibrous
      tissue content are likely to influence muscle tone and responsiveness of the
      sphincter in fecal incontinence.

PMID- 7720451
TI  - Recovery of physiologic and clinical function after low anterior resection of the
      rectum for carcinoma: myth or reality?
AB  - PURPOSE: The aim of this study was to examine the serial changes that take place
      in the first year after low anterior resection for rectal carcinoma, in terms
      both of anorectal physiology and clinical bowel function. Our hypothesis was that
      some patients never regain satisfactory anorectal function, because the operative
      procedure leads to permanent impairment of anorectal reflex and motor function.
      METHOD: Nineteen patients underwent serial tests of anorectal function, before
      and for one year after low anterior resection. The median level of the
      anastomosis above the anal high-pressure zone was 3 (range, 1-6) cm. RESULTS:
      Anal resting pressure (median (interquartile range)) was significantly decreased
      three months after operation (62 (46-72) cm H2O) and one year after operation was
      still significantly less (58 (48-73) cm H2O) than before operation (77 (58-93) cm
      H2O) (P < 0.01). Maximum tolerated volume in the neorectum decreased from 130 (88
      193) ml before operation to 80 (51-89) ml three months after operation (P <
      0.005) but returned to preoperative values by six months (125 (60-140) ml) (P =
      not significant) and remained at these values one year after operation. The
      volume in the "neorectal" balloon required to elicit a maximum rectoanal
      inhibitory reflex was significantly less three months after operation than before
      operation (50 (43-60) ml compared with 100 (73-100) ml; P < 0.005); one year
      after operation, the volume required was still significantly less than before
      operation (50 ml vs. 100 ml) (P < 0.015). Bowel frequency increased from 1 (1-2)
      in 24 hours before operation to 4 (2-5) times in 24 hours after operation and
      remained at 4 times in 24 hours throughout the first year after operation. Three
      months after operation, 53 percent of patients experienced some degree of fecal
      leakage and 24 percent experienced urgency of defecation. These aspects of bowel
      function improved with time, but even one year after operation, 29 percent of
      patients continued to experience fecal leakage and 18 percent wore a protective
      pad. CONCLUSIONS: Anal resting pressure decreased significantly after low
      anterior resection and did not recover in the course of the first year after
      operation. Moreover, the volume of an air-filled balloon in the neorectum that
      was required to elicit maximum inhibition of the anal sphincter was significantly
      less after anterior resection that before operation. These long-term and
      presumably permanent changes in physiologic behavior of the anoneorectum after
      low anterior resection provide an explanation for the failure of some patients to
      regain satisfactory bowel function following that procedure.

PMID- 7720452
TI  - What is the relationship between perineal descent and anal mucosal
      electrosensitivity?
AB  - PURPOSE: Perineal descent is found in many patients with anorectal disorders.
      There is now substantial evidence against perineal descent causing damage to the
      motor axons in the pudendal nerves, but the sensory sequelae of perineal descent
      have been neglected. The purpose of this study was to establish the relationship
      between perineal descent and anal sensation. METHODS: Perineal position was
      determined in relation to the bony pelvis by means of defecating proctography.
      Anal mucosal electrosensitivity was determined by using a constant current
      generator. RESULTS: This study demonstrated significant correlations between
      perineal position at rest and sensitivity in each third of the anal canal in the
      study group overall. In women studied alone, there were significant correlations
      between perineal position at rest and at squeeze and anal mucosal
      electrosensitivity in each third of the anal canal. CONCLUSIONS: We propose that
      perineal descent traumatizes the pudendal nerves, damaging the large diameter
      sensory axons. This may be a precursor of motor axon damage or may correlate with
      the global pelvic sensory loss found in patients with perineal descent and fecal
      incontinence.

PMID- 7720453
TI  - Ogilvie's syndrome: a new approach to an old problem.
AB  - PURPOSE: This study was designed to determine the value of intravenous
      neostigmine in achieving adequate colonic decompression in patients with
      Ogilvie's syndrome. METHODS: A prospective study was undertaken in 12 consecutive
      patients (median age, 60 (range, 38-98) years) with contrast enema-proven
      Ogilvie's syndrome (median duration, four (range, two-nine) days) RESULTS:
      Satisfactory clinical decompression of large bowel distention was attained in 11
      patients, although one required colectomy for subsequent recurrence and ischemia.
      CONCLUSION: These results support the theory that many cases of Ogilvie's
      syndrome are the result of excessive large bowel parasympathetic suppression
      rather than sympathetic overactivity.

PMID- 7720454
TI  - Diffuse microscopic angiodysplasia--a previously unreported variant of
      angiodysplasia. Report of a case.
AB  - PURPOSE: The entity of diffuse microscopic angiodysplasia is described, and a
      patient with severe gastrointestinal hemorrhage because of this submucosal source
      of bleeding is reported. METHOD: Case records of a patient with severe
      gastrointestinal hemorrhage were reviewed, and histologic findings were compared
      with colonoscopic and operative findings. The patient received 51 units of packed
      red blood cells over 3.5 months and remained undiagnosed, despite an exhaustive
      evaluation, until autopsy. RESULTS: Ectatic veins, venules, and capillaries were
      present within the submucosa in virtually every section of the small and large
      intestine examined (79 of 86 sections). Histologic evidence of bleeding from
      these submucosal vessels was identified in three sites (colon, jejunum, and
      ileum). The absence of endoscopically visible lesions was explained by findings
      that vessels did not traverse the muscularis mucosa and that mucosal depth was
      normal. This case of diffuse microscopic angiodysplasia, therefore, represents a
      unique variant, because the vascular findings were so diffuse and the mucosa
      remained histologically and endoscopically uninvolved, despite severe bleeding.
      CONCLUSION: Gastrointestinal bleeding from angiodysplasia is generally assumed to
      arise from endoscopically recognizable vascular ectasia within the mucosa. Thus,
      this case helps provide an explanation for some cases in which occult or massive
      bleeding is assumed to be secondary to angiodysplasia, even when endoscopic
      verification is not possible. Recognition of this disease process may require
      segmental resection or deep biopsy of endoscopically normal intestine.

PMID- 7720455
TI  - Simple technique for the treatment of strictured colorectal anastomosis.
AB  - A transanal alternative to open surgery is described for opening strictured
      colorectal anastomoses with an EndoGia stapler.

PMID- 7720457
TI  - Magnetic resonance imaging of fistula-in-ano.

PMID- 7720456
TI  - Current status of incidental surgery.
AB  - PURPOSE: Incidental surgery is a common occurrence in abdominal operations. This
      article is a review of recent publications on the safety and efficacy of such
      secondary procedures. METHODS: A recent review of the literature as well as
      incorporation of some original data were conducted. RESULTS: Incidental surgery
      is safe, but the indication should be clear in the surgeon's mind, including
      epidemiologic risk of disease in such organs as the gallbladder and appendix.
      CONCLUSION: Factors that must be included into a decision to perform incidental
      surgery should be the age and general health of the patient, prognosis, setting
      of the original operation (emergency vs. nonemergency), and epidemiologic risk of
      disease when incidental surgery is performed prophylactically.

PMID- 7720458
TI  - Current theories of pathogenesis and treatment of nonocclusive mesenteric
      ischemia.
AB  - Nonocclusive mesenteric ischemia (NOMI) is a poorly understood condition marked
      by progressive intestinal ischemia leading to infarction, sepsis, and death in a
      high proportion of patients. The mortality rate for this intestinal disorder
      remains high, even when the diagnosis is made early in the disease course. This
      paper presents a comprehensive review of NOMI with a detailed discussion of its
      history, pathophysiology, diagnosis, and treatment.

PMID- 7720459
TI  - Newly synthesized histamine accelerates ornithine decarboxylase activity in rat
      intestinal mucosa after ischemia-reperfusion.
AB  - We previously demonstrated that both histamine synthesis (histidine decarboxylase
      activity) and polyamine synthesis (ornithine decarboxylase activity) increased in
      the rat intestinal mucosa after ischemia-reperfusion, whereas the relationship
      between these two factors remains unclear. To elucidate this relationship, we
      performed the present study. The superior mesenteric artery was occluded for 15
      min followed by reperfusion. After ischemia-reperfusion, histidine decarboxylase
      activity and ornithine decarboxylase activity in the rat jejunal mucosa were
      measured in a time-dependent manner. Histidine decarboxylase activity increased 1
      hr after ischemia-reperfusion, although ornithine decarboxylase activity did not;
      however, its activity did increase 6 hr after. The increase of ornithine
      decarboxylase activity was attenuated when the increase of histamine synthesis
      was suppressed by the inhibition of histidine decarboxylase activity caused by
      pretreatment with alpha-fluoromethylhistidine, a suicide inhibitor of histidine
      decarboxylase. Pretreatment with H1-receptor antagonist attenuated the increase
      of ornithine decarboxylase activity after ischemia-reperfusion. These results
      indicate that the newly synthesized histamine, as indicated by an increase of
      histidine decarboxylase activity, increases ornithine decarboxylase activity
      after ischemia-reperfusion of the rat intestinal mucosa.

PMID- 7720460
TI  - Evaluation of gallbladder function before and after gastrectomy using a double
      isotope method.
AB  - The motor function of the gallbladder after partial distal gastrectomy for
      gastric carcinoma (Billroth-I reconstruction) and its relationship to the motor
      function of the stomach was investigated using a double-isotope method. In this
      method, [99mTc]N-54-pyridoxyl-5-methyltryptophan ([99mTc]PMT) was utilized as a
      tracer for the biliary tract and [111In]diethyl-triaminopontacetic acid
      ([111In]DTPA) mixed with a liquid test meal was used as a tracer for the
      digestive tract. Gastric emptying half-time (GET1/2) was measured, since this was
      used historically as the physiologic indicator of gallbladder contractile
      stimulus. The volume of test meal that emptied from the stomach into the duodenum
      per minute (VOL/MIN) was measured, as was the gastric emptying duration (GED). A
      series of gallbladder emptying phenomena were analyzed using three different
      criteria: gallbladder emptying half-time (GBET1/2), retention rate of bile in the
      gallbladder (RR), and the start of gallbladder bile ejection into the duodenum
      after ingestion (TL: time lag). While GET1/2 was reduced (P < 0.01) and VOL/MIN
      was increased (P < 0.01) after gastrectomy, GED was shortened remarkably (P <
      0.01). GBET1/2 showed no significant change, RR increased (P < 0.05), and TL was
      prolonged (P < 0.01). The postoperative dysfunction of the gallbladder was caused
      by the short and intense stimulus on the biliary tract during the duodenal phase
      and by intraoperative injury to the innervation of the gallbladder. In
      particular, the hepatic branch of the left vagus nerve was injured during the
      right paracardiac lymph node dissection performed as a component of the radical
      gastrectomy.

PMID- 7720461
TI  - Increased turnover of intrahepatic bile ducts induced by bromobenzene.
AB  - Intrahepatic bile duct epithelium consists of two kinetic compartments: a
      progenitor (P) and a functional (Q) compartment. Hitherto bromobenzene was known
      to poison only hepatocytes in the third acinus zone. The present experiment aims
      to demonstrate that bromobenzene affects also bile duct turnover. Thirty male
      adult rats received one intraperitoneal injection of bromobenzene and were
      sacrificed in groups of five at the following times: 1, 2, 3, 4, 7, and 14 days.
      They received [3H]thymidine 1 hr before sacrificing. Autoradiography was done.
      Bile ducts were evaluated in all portal tracts of the section. The number of
      epithelial cells in each duct cross section was counted and defined as bile duct
      class, which is roughly proportional to bile duct size. In each cross section the
      number of labeled cells was counted. Initially the labeling index was 0.76 +/-
      0.3%. By day 3, it reached a peak of 4.1 +/- 1.1%, and then declined to its
      initial level. Following bromobenzene poisoning, hepatocyte and bile duct
      epithelia turn over in the same fashion. In both, labeling index and progenitor
      compartment size initially rise and return by the end of the first week to their
      initial level. We propose that bile duct epithelia and hepatocytes originate in
      one determined uncommitted stem cell that resides in the Herring duct.
      Bromobenzene-induced necrosis triggers proliferation of progenitors in both cell
      lineages, as well as in the stem cell itself.

PMID- 7720462
TI  - Effectiveness of gabexate mesilate in acute pancreatitis. A metaanalysis.
AB  - Since the effectiveness of gabexate mesilate in patients with acute pancreatitis
      is controversial, a metaanalysis of the published literature was conducted to
      address this problem. Five randomized trials were identified by our literature
      search. Three end points (mortality, complications, and complications requiring
      surgery) were evaluated. The results of our metaanalysis indicate that the
      treatment with gabexate mesilate does not affect mortality at 90 days (P = 0.27),
      but significantly reduces the incidence of complications requiring surgery (odds
      ratio = 0.61, 95% CI: 0.41-0.89; P < 0.05) and of complications in general (odds
      ratio = 0.69, 95% CI: 0.54-0.89; P < 0.05). Because the drug proves to be
      beneficial only to a low proportion of the treated patients, its clinical impact
      seems to be small. A pharmacoeconomic evaluation shows that its use in all
      patients with acute pancreatitis would imply a very high cost for preventing each
      complication. The administration of the drug to select patients who are at higher
      risk of complications could have a better cost-effectiveness ratio. However,
      specific studies on this point are still lacking.

PMID- 7720463
TI  - Preduodenal mechanisms compensate completely for absent pancreatic enzymes to
      stimulate gallbladder after meals.
AB  - We studied gallbladder emptying with gamma scintigraphy in nine dogs prepared
      with chronic pancreatic fistulas, so that pancreatic enzymes could be either
      completely excluded from the duodenum or supplied in normal amounts. During
      duodenal perfusion of the fasted dogs with fat emulsions, gallbladder emptying
      was significantly less rapid when the emulsion contained inactive vs active
      enzymes, confirming the potency of lipolytic products in the intestine as stimuli
      of gallbladder emptying. However, after feeding either a 115-g or a 460-g meal,
      each 18% fat, the gallbladders emptied identically whether or not pancreatic
      enzymes were excluded from the duodenum. We concluded that while products of
      pancreatic lipolysis in the small intestine are potent stimuli of gallbladder
      contraction, preduodenal mechanisms can compensate completely for the absence of
      pancreatic hydrolysis in stimulating gallbladder emptying after a meal.

PMID- 7720464
TI  - Effect of gastric distension and duodenal fat infusion on biliary sphincter of
      Oddi motility in healthy volunteers.
AB  - Although sphincter of Oddi (SO) dysfunction has been implicated in the
      pathogenesis of postcholecystectomy syndrome and pancreatitis, little is known
      about normal physiologic stimuli, such as intraduodenal fat on human SO motility.
      Furthermore, gastric distension that frequently accompanies endoscopic manometry
      has been shown in animal studies to affect SO motility. We evaluated the effects
      of intraduodenal fat and gastric distension on SO basal pressure. Asymptomatic
      volunteers had SO manometry performed while sequentially performing gastric
      distension and intraduodenal fat perfusion. Five subjects (ages 29.8 +/- 4.8
      years, range 22-35 years) had a mean basal sphincter of Oddi pressure of 23.4 +/-
      5 mm Hg (range 17-31 mm Hg). Injection of air into the stomach caused no
      appreciable change in either intragastric pressure or SO pressure. Intraduodenal
      fat infusion resulted in a decrease in mean SO basal pressure from 23.4 +/- 5.0
      to 4.4 +/- 4.4 mm Hg (P = 0.004). These results demonstrate that gastric
      distension does not affect SO basal pressure and that intraduodenal fat infusion
      reduces SO basal pressure.

PMID- 7720465
TI  - Schonlein-Henoch purpura and pancreatitis.

PMID- 7720466
TI  - Regression of inflammatory pseudotumor of the liver under conservative therapy.
AB  - Inflammatory pseudotumors (IPT) of the liver are rare benign tumors of unknown
      origin. Most previously reported cases were initially misdiagnosed and treated
      surgically; thus, their course under medical treatment remains unclear. We report
      an additional case of hepatic IPT with a favorable outcome under medical
      treatment without surgical resection. New imaging and pathologic features of this
      disease are presented that may facilitate preoperative recognition and
      appropriate treatment.

PMID- 7720467
TI  - A lectin histochemical study of intrahepatic ducts in patients with
      hepatolithiasis.
AB  - A panel of 12 biotinylated lectins was used to investigate the diversity of
      glycoconjugate on the epithelium of stone-containing intrahepatic bile ducts and
      compared to controls. Among the 12 lectins, only WGA (wheat germ agglutinin) and
      Con A (concanavalin agglutinin) stained the epithelium of stone-containing
      intrahepatic ducts. Con A, a glucose/mannose-specific lectin, bound weakly on the
      epithelium of the stone-bearing intrahepatic duct in 10 of the 25 specimens, but
      none of the controls. All stone-containing intrahepatic bile ducts were stained
      heavily and homogenously by WGA, the N-acetylglucosamine-specific lectin. The
      high columnar epithelia of both intramural and extramural glands were stained in
      the supranuclear region, while the serous acini of extramural glands were stained
      in whole cytoplasm. The epithelium of intrahepatic ducts from the controls was
      stained weakly by WGA only. The WGA receptors were not abolished by pretreatment
      of neuraminidase. This led us to conclude that the stone-containing intrahepatic
      ducts were rich in N-acetylglucosamine and the heavy and homogenous staining with
      WGA will be indicative of hypersecretion of mucus from stone-bearing intrahepatic
      bile ducts.

PMID- 7720468
TI  - Posttransfusional, LKM-1-autoantibody-positive hepatitis C virus infection,
      cryoglobulinemia, and aplastic anemia.
AB  - Aplastic anemia is occasionally caused by viral hepatitis, hepatitis C virus
      being the most important factor. Pathogenetically, decreased bone marrow
      function, abnormalities of the bone marrow microenvironment, and immune-mediated
      suppression of hematopoiesis are important. Hepatitis C virus infection is
      associated with a variety of extrahepatic manifestations including autoimmune
      features like cryoglobulinemia, Sjogren's syndrome, and autoimmune hepatitis.
      Here we report the case of a 42-year-old man with aplastic anemia due to
      posttransfusional hepatitis C virus infection associated with cryoglobulinemia
      and LKM-1 autoantibodies. Following a triple immunosuppressive therapy, there was
      a complete reconstitution of the bone marrow. Serum HCV-RNA as well as plus- and
      minus-stranded HCV-RNA in peripheral blood mononuclear cells (PBMC) were detected
      before immunosuppressive therapy. After therapy, serum HCV-RNA persisted.
      Furthermore, PBMC now were positive for plus-stranded RNA only. However, in bone
      marrow-derived precursor cells we failed to demonstrate HCV molecules after
      therapy. This would argue for reconstituted PBMC from newly generated uninfected
      precursor cells. It remains unclear as to whether the autoimmune character of the
      disease or the hepatitis C virus infection itself have contributed to the
      pathogenesis of the aplastic anemia.

PMID- 7720469
TI  - Na+/H+ exchange mediates postprandial ileal water and electrolyte transport.
AB  - Feeding stimulates fluid and electrolyte absorption in the small intestine.
      Previous studies have suggested that Na+/glucose cotransport is important in
      initiating this response in the jejunum. The purpose of this study was to
      determine whether Na+/H+ exchange plays a role in meal-induced absorption.
      Exteriorized, neurovascularly intact jejunal and ileal loops (25 cm) were
      constructed in dogs. Following a two-week period of postoperative recovery, the
      loops of awake dogs were perfused with standard buffer alone or with increasing
      concentrations of amiloride, a Na+/H+ exchange inhibitor. Water, sodium, and
      chloride fluxes were calculated following a meal using [14C]PEG as a volume
      marker. The meal significantly increased absorption in both the jejunum (P <
      0.001) and ileum (P < 0.01) in those animals perfused with buffer alone. More
      significantly, amiloride suppressed the increased absorption seen following a
      meal in the ileum (P < 0.001) but not the jejunum. The response in the ileum was
      dose dependent. These findings suggest that a major mediator of postprandial
      sodium and water absorption in the ileum is the Na+/H+ exchanger.

PMID- 7720470
TI  - Should interdigestive motility of small intestine be recorded by long-term
      ambulatory or short-term stationary manometry?

PMID- 7720471
TI  - Serum concentrations of von Willebrand factor and soluble thrombomodulin indicate
      alteration of endothelial function in inflammatory bowel diseases.
AB  - Serum concentrations of immunoreactive von Willebrand factor (vWF) and soluble
      thrombomodulin (TM), and vWF multimer patterns were measured to assess
      endothelial function in patients with inflammatory intestinal diseases. In
      Crohn's disease and acute infective diarrhea, vWF concentrations were
      significantly higher than in normal controls. In all patient groups, multimeric
      analysis of vWF and the concentration of serum TM were not different from normal
      controls. The results indicate alteration of endothelial function in inflammatory
      intestinal disorders. They may be compatible with the presence of localized
      vasculitis, but indicate that systemic endothelial destruction does not occur in
      inflammatory bowel disease.

PMID- 7720472
TI  - Prospective evaluation of interferon-alpha in treatment of chronic active Crohn's
      disease.
AB  - Several case reports suggested good effects of interferon-alpha in patients with
      Crohn's disease. In addition, a decreased production of interferon-alpha in
      Crohn's disease has been shown in vitro. Treatment with interferon-alpha may
      activate intestinal natural killer cells and down-regulate the overproduction of
      inflammatory cytokines like interleukin-6 in Crohn's disease. To evaluate the
      clinical efficacy of interferon-alpha, we treated 12 patients with a chronic
      active course of Crohn's disease with recombinant human interferon-alpha
      prospectively for 24 weeks. Prednisolone was continuously tapered and
      discontinued at week 12. The end point of the study was the prevention of
      worsening of clinical symptoms defined with the Crohn's disease activity index
      and was monitored by acute-phase proteins, interleukin-6 serum concentrations,
      and endoscopy. The biochemical activity of interferon-alpha was measured by 2',5'
      oligo adenylate serum levels. The end point of the study was reached in four
      patients (33%). In these patients the final Crohn's disease activity index was
      above 150, which means that they did not achieve clinical remission. All other
      patients (66%) did not respond to interferon-alpha and had to be withdrawn
      prematurely. Interferon-alpha did not show any beneficial effect on interleukin-6
      or acute-phase protein concentrations and on endoscopic activity. The 2',5'-oligo
      adenylate levels continuously increased during interferon therapy. Considerable
      side effects were noted. These results fail to demonstrate a therapeutic role of
      interferon-alpha in chronic active Crohn's disease.

PMID- 7720473
TI  - Decreased mucosal IgA levels in ileum of patients with chronic ulcerative
      colitis.
AB  - Patients with chronic ulcerative colitis (CUC) are known to have decreased
      spontaneous IgA secretion by colonic mononuclear cells. The aim of this study was
      to determine whether a similar alteration exists in the apparently healthy ileum
      of patients with CUC. The concentration of IgA was measured in the supernatant
      from homogenized mucosal ileal biopsies using a sandwich-type ELISA. The
      concentration of IgA was significantly (P = 0.025) decreased in the ileum of
      patients with CUC (N = 24) in comparison to normal ileum (N = 10). The number of
      mucosal IgA-containing mononuclear cells (MNC) was also determined using an
      avidin-biotin-immunoperoxidase technique on paraffin-embedded ileal sections.
      Although reduced, the number of positive cells and their distribution was not
      significantly different in the ileum of patients with CUC (N = 20) when compared
      to normal ileum (N = 10). We suggest that decreased mucosal IgA levels are a
      panintestinal condition in CUC and that this is a primary alteration rather than
      a secondary response to the inflammatory process. Considering the role of IgA, we
      propose that decreased mucosal IgA levels in CUC may predispose to the disease by
      a reduction of the immune-mediated exclusion mechanism and/or by an impairment of
      the down-regulation of the inflammatory response.

PMID- 7720474
TI  - Ileal intussusception and obstruction as presentation of inflammatory fibroid
      polyp.

PMID- 7720475
TI  - HLA-DRB1*1502 allele, subtype of DR15, is associated with susceptibility to
      ulcerative colitis and its progression.
AB  - HLA-DRB1 allele typing was performed by the PCR-RFLP method on 59 ulcerative
      colitis (UC) patients and 136 healthy controls. Phenotypic frequencies of HLA-B52
      and DR2 were significantly increased among the UC patients, serologically. DNA
      typing of HLA-DRB1 revealed that the genotypic frequency of DRB1*1502 was higher
      in UC than in the controls (49.2% vs 17.6%; P < 0.0001). In the analysis of
      clinical parameters, 82.8% of patients bearing DRB1*1502 were treated with
      corticosteroids. DRB1*1501 and DRB1*1502 differ in only one amino acid at residue
      86 (valine vs glycine), and 66% of the UC patients carried two glycines at
      position 86 in the HLA-DR beta-chain (vs 51% of control; P < 0.05). These
      observations suggest that the presence of Gly-86 in the HLA beta-chain and
      surrounding amino acid sequence of HLA-DRB1*1502 is strongly associated with
      susceptibility to UC.

PMID- 7720476
TI  - Visceral perception in irritable bowel syndrome. Rectal and gastric responses to
      distension and serotonin type 3 antagonism.
AB  - We wished to determine if visceral perception in the rectum and stomach is
      altered in patients with irritable bowel syndrome and to evaluate the effects on
      visceral sensation of 5-HT3 receptor blockade. Twelve community patients with
      diarrhea-predominant irritable bowel syndrome and 10 healthy controls were
      studied in a double-blind, randomized, placebo-controlled study. Using two
      barostats, the stomach and rectum were distended, with pressure increments of 4
      mm Hg, from 10 to 26 mm Hg; visceral perception was measured on an ordinal scale
      of 0-10. Personality traits were measured using standard psychological methods,
      and somatic pain was evaluated by immersion of the nondominant hand in cold
      water. The effect of 5-HT3 antagonism was tested with a single intravenous dose
      of ondansetron at 0.15 mg/kg. Gastric perception was higher in irritable bowel
      syndrome, but rectal distension was perceived similarly in irritable bowel
      syndrome and controls. Pain tolerance to cold water was also similar in irritable
      bowel syndrome and controls. Ondansetron induced rectal relaxation and increased
      rectal compliance but did not significantly alter gastric compliance or visceral
      perception. Psychological test scores were similar in patients and controls. We
      conclude that in this group of psychologically normal patients with irritable
      bowel syndrome, who were not chronic health-care seekers, visceral perception was
      normal. Ondansetron did not alter gut perception in health or in irritable bowel
      syndrome.

PMID- 7720477
TI  - Effect of streptozotocin-induced diabetes mellitus on release of vasoactive
      intestinal polypeptide from rodent small intestine.
AB  - Representative longitudinal muscle strips (6 x 10 mm) from proximal and distal
      small intestine were excised from control and streptozotocin-treated rats after
      one month of untreated and insulin-treated diabetes. Untreated diabetes
      significantly reduced tissue concentrations of vasoactive intestinal polypeptide
      (VIP) at both intestinal loci. Insulin treatment of the diabetic animals restored
      tissue VIP concentrations to control group levels, although the beneficial effect
      of insulin treatment was only significant in the duodenum. Spontaneous release of
      VIP was significantly attenuated by untreated diabetes at both intestinal sites.
      In the duodenum, insulin treatment of the diabetic animals restored VIP release
      to levels indistinguishable from control group values. In the ileum, insulin
      treatment produced levels of VIP release that were not significantly different
      from those of the control and untreated diabetic groups. Tetrodotoxin (5 x 10(-6)
      M) significantly--but incompletely--inhibited VIP release from control group
      animals at both intestinal sites. These observations indicate that diabetes
      mellitus significantly diminishes VIP tissue concentrations and release from
      intestinal myenteric nerves. These abnormalities improve with insulin treatment.
      However, the mechanisms of VIP release from proximal and distal intestine appear
      to differ not only in their response to the diabetic state, but also in their
      response to insulin treatment.

PMID- 7720478
TI  - Esophageal Crohn's disease: treat the inflammation, not just the symptoms.

PMID- 7720479
TI  - Nonhereditary colonic angiodysplasias: histomorphometric approach to their
      pathogenesis.
AB  - The pathogenesis of colonic angiodysplasias, more accurately termed vascular
      ectasias (VE) has not been definitely established. The aim of this study was to
      assess that the VE of noncirrhotic patients are not associated with diffuse
      abnormalities of the colonic mucosal microvasculature unlike the VE of cirrhotic
      patients. Three groups of nine consecutive patients were studied: group I,
      control patients with an irritable bowel syndrome; group II, noncirrhotic
      patients with VE; and group III, alcoholic cirrhotics with VE. A
      histomorphometric analysis of normal-appearing colonic mucosa was achieved from
      biopsies taken at six predetermined sites. Noncirrhotics with VE had a
      significantly lower mean number of mucosal capillaries and a significantly lower
      mean cross-sectional area of mucosal capillaries than alcoholic cirrhotics with
      VE. Alcoholic cirrhotics with VE had a significant increase of all the vascular
      parameters compared to the control group. There was no difference between the
      control patients and the noncirrhotic patients with VE. These results suggest
      that the VE of noncirrhotic and cirrhotic patients are entities of distinct
      pathogenesis.

PMID- 7720480
TI  - Intense nutritional support in inflammatory bowel disease.
AB  - The value of intense nutritional support in inflammatory bowel disease is still
      debated. Claims have been made that total enteral nutrition is as effective as
      total parental nutrition. In this review, the use of parenteral and enteral
      nutritional support as primary therapy in patients with inflammatory bowel
      disease has been critically evaluated. Most studies have been uncontrolled and
      nonrandomized with short-term follow-up. The literature does suggest, however,
      that intense nutritional support may have an adjunctive role to drug therapy in
      achieving remission in Crohn's disease, especially in corticosteroid-refractory
      patients. Nutritional support has a lesser role in chronic ulcerative colitis,
      except for assistance in pre- and postoperative management. The data do not
      support one variety of nutritional support over another, although enteral support
      should be used if possible, as it is less costly and potentially less
      complicated.

PMID- 7720481
TI  - In vitro free radical production in rat esophageal mucosa induced by nicotine.
AB  - Oxidative stress induced by nicotine was investigated in the esophageal mucosa of
      rats. The homogenized mucosa was incubated for 30 min with 50, 100, 200, 400, and
      800 ng/mg protein/ml nicotine or with 200 ng/mg protein/ml nicotine for 15, 30,
      45, and 60 min. Esophageal mucosa was also incubated for 30 min with 200 ng/mg
      protein/ml nicotine with or without the scavengers superoxide dismutase (SOD),
      catalase, SOD+catalase, inactivated SOD, inactivated catalase, or albumin.
      Incubation with 0.9% NaCl served as control. There was a strong correlation
      between chemiluminescence and the nicotine dose (r = 0.75) or the nicotine
      incubation time (r = 0.77). Thirty-minute incubation of the esophageal mucosa
      with 200 ng/mg protein/ml nicotine increased chemiluminescence 5.5-fold and lipid
      peroxidation 3.3-fold. This response was dampened by SOD or catalase and
      abolished by SOD+catalase. Inactivated enzymes or albumin had no scavenging
      effect. These results demonstrate that nicotine causes oxidative stress to the
      esophageal mucosa.

PMID- 7720482
TI  - Are human herpes viruses or measles virus associated with esophageal achalasia?
AB  - In order to test the hypothesis that esophageal achalasia may be due to
      neurotropic viral damage to the esophageal myenteric plexus, esophageal tissue
      with or without achalasia was analyzed by polymerase chain reaction for the
      presence of human herpes virus DNA or measles virus RNA. The DNA and RNA were
      extracted from the esophageal muscle of 12 patients with achalasia and six
      patients with upper esophageal carcinoma. Peripheral blood mononuclear cells from
      eight adult volunteers and two samples of umbilical blood mononuclear cells were
      also used as controls. PCR amplification with a pair of primers specific for
      herpes simplex type 1 and 2 viruses identified 92-bp fragments in nearly all
      specimens, including those without achalasia. Each 92-bp fragment was confirmed
      to be identical to a single herpes simplex virus sequence by automated DNA
      sequence analysis. No amplification for five other herpes viruses or measles
      virus was detected. Therefore, a specific viral etiology for achalasia was not
      identified in this study.

PMID- 7720483
TI  - Mechanism of gastric alkaline response in the stomach after damage. Roles of
      nitric oxide and prostaglandins.
AB  - The gastric mucosa responds to hypertonic NaCl by significantly decreasing acid
      secretion. We examined the role of nitric oxide (NO) in this phenomenon in
      comparison with endogenous prostaglandins (PGs). A rat stomach was mounted in an
      ex vivo chamber, perfused with saline, and the potential difference (PD), pH, and
      acid/alkaline responses were measured before and after the application of
      hypertonic NaCl (1 mol/liter) with or without pretreatment with NG-nitro-L
      arginine methyl ester (L-NAME; an inhibitor of NO biosynthesis) or indomethacin
      (a cyclooxygenase inhibitor). NaCl at 1 M caused a PD reduction, a decrease in
      acid secretion, and an increase in luminal HCO3-. Prior administration of L-NAME
      (5 mg/kg, intravenously) as well as indomethacin (5 mg/kg, subcutaneously) did
      not affect PD and HCO3- responses, but significantly attenuated the inhibitory
      effect of 1 M NaCl on acid secretion, although the effect of L-NAME was more
      potent when compared to indomethacin. This effect of L-NAME was antagonized by
      the simultaneous administration of L-arginine but not by D-arginine (200 mg/kg,
      intravenously), whereas the effect of indomethacin was completely reversed by
      PGE2 (100 micrograms/kg, intravenously). The histamine-stimulated acid secretion
      in the normal stomach was significantly decreased by nitroprusside (the exogenous
      NO donor; 4 mg/kg, intravenously) and PGE2, but not by either L-NAME or
      indomethacin. These results suggest that in addition to PGs, NO is involved in
      the mechanism of the gastric alkaline response after damage with 1 M NaCl.
      Irritation of the gastric mucosa by hypertonic NaCl may release endogenous NO and
      PGs, both of which in turn inhibit acid secretion and unmask luminal
      alkalinization due to HCO3- flux in the damaged portion.

PMID- 7720484
TI  - Adaptive cytoprotection in cultured rat gastric mucus-producing cells. Role of
      mucus and prostaglandin synthesis.
AB  - In cultured gastric mucosal cells, we investigated whether: (1) adaptive
      cytoprotection was associated with stimulation of endogenous prostaglandin
      synthesis; (2) prostaglandins given exogenously were cytoprotective against
      ethanol-induced gastric mucosal cell damage; and (3) a relationship existed
      between cytoprotection and mucus release. Cytolysis was quantified by measuring
      51Cr release from prelabeled cells. Mucus release was determined by measurement
      of [3H]glucosamine release. Concentrations of ethanol > 12% caused cell damage
      and increased 51Cr release dose dependently. Pretreatment with low concentrations
      of ethanol (0.5-1.5%) decreased ethanol-induced 51Cr release, but also decreased
      prostaglandin E2 synthesis. Prostaglandin E2 and 16,16-dimethyl prostaglandin E2
      given exogenously were cytoprotective against ethanol-induced gastric mucosal
      cell damage. Treatment with low concentrations of ethanol (1.5%) increased mucus
      release from cultured gastric mucosal cells. However, prostaglandin E2 and 16,16
      dimethyl prostaglandin E2 did not affect mucus release. We conclude that in
      cultured gastric mucus-producing cells: (1) adaptive cytoprotection occurs
      without stimulation of endogenous prostaglandin synthesis but with increase in
      mucus release; and (2) exogenous prostaglandins are cytoprotective against
      ethanol-induced gastric mucosal cell damage without stimulating mucus release in
      vitro. We postulate that adaptive cytoprotection in cultured gastric mucus
      producing cells is not mediated by prostaglandin, but by mucus released in
      response to a mild irritant.

PMID- 7720486
TI  - Duodenal ulcer. Calcium status in isolated parietal cells.
AB  - Although the etiology of duodenal ulcer is not known, its treatment with drugs
      that reduce acid secretion is well accepted. The central role of calcium in
      stimulus-secretion coupling resulting in acid secretion by gastric parietal cells
      is documented. However, the status of intracellular calcium in gastric parietal
      cells in the basal state in patients with duodenal ulcer is not known. Multiple
      endoscopic gastric mucosal biopsies from the corpus of the stomach of 52 patients
      were processed and isolated parietal cells were studied. Intracellular calcium
      was estimated using fura-2-acetoxymethyl ester. Influx and efflux were determined
      by using radioactive calcium. Acridine orange retention was used to assess acid
      production. Only calcium influx at 20 min was significantly (P < 0.01) more in
      patients with duodenal ulcer as compared to the control group. There was no
      difference between the groups in calcium influx at 0 and 60 min; calcium efflux
      at 0, 20, and 60 min; intracellular free calcium and acid secretion. We conclude
      that in the unstimulated state calcium homeostasis in isolated parietal cells of
      patients with duodenal ulcer shows only a minimal difference as compared to
      controls.

PMID- 7720485
TI  - Protection of cultured rat gastric cells against oxidant stress by iron
      chelation. Role of lipid peroxidation.
AB  - Reactive oxygen metabolites may be involved in the pathogenesis of ethanol-,
      nonsteroidal antiinflammatory drug-, Helicobacter pylori-, or
      ischemia/reoxygenation-induced gastric mucosal injury in vivo. Iron plays a
      critical role in mediating oxidant injury in vitro. The present study examined a
      possible role of lipid peroxidation in inducing oxidant damage by determining the
      effect of iron chelation on cytotoxicity and on lipid peroxidation in cultured
      rat gastric cells. Cytotoxicity was quantified by 51Cr release from prelabeled
      cells that were exposed to tert-butyl hydroperoxide (tBHP) so as to overwhelm the
      glutathione redox cycle. Lipid peroxidation was assessed by measuring
      malondialdehyde (MDA) production. tBHP caused a time-related and dose-dependent
      increase of 51Cr release. The presence of phenanthroline (a chelator of Fe2+)
      during tBHP exposure and pretreatment with deferoxamine (a chelator of Fe3+)
      reduced tBHP-induced 51Cr release dose dependently. The generation of MDA
      increased as the concentrations of tBHP increased, but in a time course study,
      such generation preceded cytolysis. Both iron chelators attenuated MDA production
      in a dose-dependent fashion. Oxidant stress causes lipid peroxidation in cultured
      gastric cells, which is then followed by cytolysis. Iron plays a critical role in
      inducing lipid peroxidation as well as in mediating cytolysis. Iron chelation
      protects these cells from oxidant stress presumably through inhibition of lipid
      peroxidation.

PMID- 7720487
TI  - Electrogastrography prior to and following total gastrectomy, subtotal
      gastrectomy, and gastric tube formation.
AB  - On electrogastrography (EGG) spectral analysis, an activity of 3 cycles per
      minute (cpm) is supposed to be specific for the stomach. After total or subtotal
      gastrectomy, the original site of the stomach is occupied mainly by the
      intestine. We attempted to determine if intestinal activity could be recorded in
      this region with EGG. Epigastric recordings were performed in patients prior and
      following gastrointestinal or control surgeries. Spectral analysis, using the
      maximal entropy method and ensemble means was applied to data analysis from these
      recordings. Preoperatively, the majority of the power peaks were found around 3,
      6, and 11 cpm. The postprandial-to-fasting power ratio of all of these power
      peaks increased significantly postprandially (P < 0.05-0.01). Following total
      gastrectomy, the power peak around 3 cpm disappeared or was significantly
      diminished in amplitude (P < 0.05). The postoperative-to-preoperative power ratio
      ranged from 0.03 to 0.10 (P < 0.001-0.01). However, the power peak around 11 cpm
      did not significantly change prior to or following total gastrectomy, and the 11
      cpm peak appeared relatively dominant. Simultaneous manometric studies in the
      Roux limb demonstrated a correlation between the power spectral frequency of EGG
      and manometry at 11 cpm. Therefore, the 11 cpm peak appeared to reflect jejunal
      or Roux limb electrical activity. The postoperative to preoperative power ratio
      for the 3 cpm also was significantly reduced following subtotal gastrectomy and
      gastric tube formation in patients in the postprandial state (P < 0.05-0.001).

PMID- 7720488
TI  - Effect of cisapride on myoelectrical and motor responses of antropyloroduodenal
      region during intraduodenal lipid and antral tachygastria in conscious dog.
AB  - The myoelectrical and motor response of the antropyloroduodenal region to
      intraduodenal nutrient stimulation or antral tachygastria represent useful models
      for, respectively, physiological and pathophysiological gastric stasis to test
      the efficacy of prokinetic drugs. We evaluated the effects of an intravenous
      bolus of cisapride (0.63 mg/kg) on the myoelectrical and motor response of the
      antropyloroduodenal region to an intraduodenal triglyceride emulsion (10%
      Intralipid, 0.5 ml/min) or antral tachygastria in conscious dogs. Intraduodenal
      lipid suppressed antral motility (P < 0.05, compared to intraduodenal saline) and
      stimulated phasic pyloric contractions (P < 0.01, compared to intraduodenal
      saline), a motor pattern known to be associated with delayed gastric emptying.
      During intraduodenal lipid stimulation cisapride virtually abolished all isolated
      pyloric motor events (P < 0.05) and stimulated antral and duodenal motility (P <
      0.05 for both) and antropyloroduodenal coordination (65% versus 15%; P < 0.05).
      Antral tachygastria was associated with a higher number of isolated pyloric motor
      events in the fasted state [0.8 (0.7-1.1) per minute versus 0.2 (0-0.3) per
      minute; P < 0.05], but not during intraduodenal lipid stimulation [1.1 (0.9-1.7)
      per minute versus 1.2 (1.0-1.9) per minute; NS]. Cisapride decreased the number
      and duration of spontaneous episodes of antral tachygastria during intraduodenal
      saline and lipid infusion (P < 0.05 for both) and abolished the tachygastria
      associated motor patterns. Cisapride induced a 20% decrease in the antral slow
      wave frequency during intraduodenal saline and lipid, irrespective of gastric
      pacemaker rhythm. We conclude that: (1) cisapride overcomes feedback from small
      intestinal lipid receptors on myoelectrical and motor activities of the
      antropyloroduodenal region and decreases antral slow-wave frequency, and (2)
      cisapride inhibits antral tachygastria and tachygastria-associated motor
      patterns. These effects may contribute to the effective gastrokinetic properties
      of cisapride in physiological and certain forms of pathophysiological gastric
      stasis.

PMID- 7720489
TI  - Helicobacter pylori gastritis therapy with omeprazole and clarithromycin
      increases serum carbamazepine levels.
AB  - An antibiotic combination that includes a proton pump inhibitor such as
      omeprazole and an antibiotic such as clarithromycin is likely to become the new
      standard regimen for treatment of Helicobacter pylori gastritis because this
      combination is extremely effective and very well tolerated. The current report
      highlights a potentially significant pharmakokinetic drug interaction between
      clarithromycin and carbamazepine in two patients with long-standing epilepsy who
      were given such therapy for Helicobacter pylori gastritis. In both cases,
      clarithromycin therapy was temporally related to an increase in serum
      carbamazepine levels, which returned to the therapeutic range following cessation
      of clarithromycin therapy. The potential implications of this newly recognized
      drug interaction are discussed.

PMID- 7720490
TI  - Diffuse muscular thickening of esophagus associated with multiple leiomyomas
      diagnosed by endoscopic ultrasonography.

PMID- 7720491
TI  - [The expression of 67-KD laminin receptor (LN-R) gene in PG tumor cells with high
      metastatic potential].
AB  - The expression level of 67-KD LN-R mRNA was observed in high-metastatic PG tumor
      cells and low-metastatic PAa tumor cells based on the cDNA fragments of 67-KD LN
      R amplified by PCR technique and the specific cDNA probe prepared by random
      primer labeling method. Results showed that the transcripts were homologous in
      size, about 1.7kb, in PG and PAa tumor cells. The 67-KD LN-R mRNA level was
      higher in PG than that in PAa tumor cells, and gene amplification was also more
      marked in PG tumor cells. After treated with 67-KD LN-R monoclonioal antibody
      (50, 100 and 400 micrograms/ml) for 48 hours, LN-R mRNA of PG tumor cells
      decreased significantly. It is suggested that 67-KD LN-R may play important roles
      in metastatic processes of PG tumor cells.

PMID- 7720492
TI  - [Alterations of oncogenes in human fetal esophageal epithelium induced by N
      methylbenzylnitrosamine (NMBzA)].
AB  - Epidemiological investigation showed that N-methylbenzylnitrosamine (NMBzA) has
      been associated with increased incidence of esophageal cancer (EC) in Linxian
      county, a high incidence area. In present study, our results indicate that NMBzA
      can induce amplification and over-expression of EGFr gene in human fetal
      esophageal epithelium (HFE) treated with NMBzA for 24 hours as shown by southern
      blot assay and immunohistochemistry. The papillary hyperplasia was induced in
      HFEs that cultured with NMBzA for 1 to 3 weeks. Amplification of c-myc and int-2
      gene in HFEs treated by NMBzA for 1 week and 3 weeks was found, respectively.
      Deletions of p53 and Rb gene were found in human fetal esophageal carcinomas
      induced by NMBzA. Overexpression of p53 protein in human fetal esophageal
      carcinomas detected by immunohistochemical methods indicates that p53 gene
      mutation(s) may be occured. The HFE explants treated in vitro with NMBzA for 3
      weeks were inoculated subcutanously into balb/c nude mice. No tumor was found in
      5 months after inoculation, suggesting that only changes of oncogene(s) are
      insufficient to induce full transformation. Other genetic alterations (such as
      functional inactivation of Rb or/and p53 tumor suppressor genes) may be necessary
      in the further progression of malignant lesions.

PMID- 7720493
TI  - [Clinical studies on serum glutathione S-transferase level in human breast cancer
      patients].
AB  - The level of serum Glutathioe S-transferase (GSTs) was first measured in 224
      female patients with breast cancer and 17 patients with benign breast tumor and
      96 normal female subjects. The relationship between serum GSTs and biological
      characteristics of breast cancer was studied. The mean serum GSTs in patients
      with breast cancer was 1.22 +/- 1.44 ng/ml. The positive rate was 51.8%. The
      level of serum GSTs in the patients with breast cancer was significantly higher
      than in normal subjects and patients with benign breast tumor. No correlation was
      found with regard to the level of serum GSTs, the size of the breast cancer,
      stage, lymphatic metastasis and estrogen receptor status. Serum GSTs level is
      thus of little value in the evaluation of response and prognosis of breast
      cancer.

PMID- 7720494
TI  - [Some immune functions of patients with carcinoma].
AB  - To evaluate efficiency of LAK cells from patients with cancer a number of immune
      functions of patients with advanced carcinoma was investigated. The results
      showed that: from patients with cancer, lymphocyte transformation (32.83 +/-
      52.59), responses of lymphocytes to IL-2 (5.94 +/- 9.31), and to IL-2/PHA (32.25
      +/- 43.05), and NK activity (11.18 +/- 6.98), LAK activity (17.86 +/- 9.57) were
      significantly suppressed (In the healthy donors, the data were 75.70 +/- 52.65,
      24.59 +/- 28.25, 125.47 +/- 74.11 respectively, P < 0.001); sIL-2R and TNF
      concentrations (241.9 +/- 172.5 pmol/L and 1.86 +/- 1.52 ng/ml respectively) in
      serum from patients with cancer were significantly higher than that of healthy
      control (134.2 +/- 73.5 pmol/L and 0.63 +/- 0.20 ng/ml respectively, P < 0.05
      0.001). Since patients with cancer had suppressed responses of lymphocytes to IL
      2, low NK and LAK cell activity, LAK cells from patients with cancer might be
      less effective than those from healthy donor in the treatment of cancer.

PMID- 7720495
TI  - [Experimental study on the pharmacologic effects of zeng sheng pin pian].
AB  - Zeng Sheng Pin Pian (ZSPP) is a mixture of medicinal herbs which has been shown
      to be effective in the secondary prevention of esophageal cancer in a high-risk
      area among a population with severe esophageal dysplasia. This study in mice
      aimed at elucidating the possible mechanism of the cancer-preventing activity of
      ZSPP. The results indicate that ZSPP is a good biologic response modifier (BRM)
      as shown by its enhancing effects on lymphocyte blastogenesis, IL-2 secretion, NK
      cell activity, delayed-type hypersensitivity reaction to DNCB, hemolysin response
      to SRBC and the phagocytic function of the reticulo-endothelial system. While
      ZSPP did not inhibit the growth of S-180 in mice, it exhibited significant
      inhibitory effect on ornithine decarboxylase (ODC) activity induced by the
      application of croton oil to the skin. Taken together, the immune enhancing
      activity and the anti-tumor-promoting activity of ZSPP could explain, at least in
      part, its efficacy in the prevention of esophageal cancer among high-risk people
      with precursor dysplastic lesions.

PMID- 7720496
TI  - [Analysis of the characteristics of human papilloma virus infection in 85
      neoplasms of the respiratory system in adult patients].
AB  - Eighty five neoplastic tissues of respiratory system in Chinese adult patients
      were searched for HPV by multiple PCR and in situ hybridization. In 13 of the
      specimens examined, HPV DNA was identified (15.3%), including 6 of 36 cases of
      pharyngolaryngeal neoplasms (16.6%) and 7 of 49 cases of lung squamous cell
      carcinomas (14.2%). Among the 13 cases tumor specimen, most of them were positive
      for HPV6/11 types and a few were double positive for HPV 6/11 and 16 types. Many
      tumor cells positive for HPV DNA on in situ hybridization were morphologically
      similar to those koilocytes in genital condylomas. HPV infection in 85 neoplasms
      was characterized by the fact that the same genotypes of HPV were detected in
      upper and lower respiratory tract and that the dominant virus types detected were
      HPV 6/11 types. The detection rate of HPV was a little higher in the upper than
      that in the lower respiratory tract and the HPV DNA positive tumors had similar
      histological appearance. The results suggest that HPV infection in the neoplasms
      of the upper and the lower airways is related to each other with similar mode of
      transmission.

PMID- 7720497
TI  - [Observation of the effects of LAK/IL-2 therapy combining with Lycium barbarum
      polysaccharides in the treatment of 75 cancer patients].
AB  - Seventy nine advanced cancer patients in a clinical trial were treated with
      LAK/IL-2 combining with Lycium Barbarum polysaccharides (LBP). Initial results of
      the treatment from 75 evaluable patients indicated that objective regression of
      cancer was achieved in patients with malignant melanoma, renal cell carcinoma,
      colorectal carcinoma, lung cancer, nasopharyngeal carcinoma, malignant
      hydrothorax. The response rate of patients treated with LAK/IL-2 plus LBP was
      40.9% while that of patients treated with LAK/IL-2 was 16.1% (P < 0.05). The mean
      remission in patients treated with LAK/IL-2 plus LBP also lasted significantly
      longer. LAK/IL-2 plus LBP treatment led to more marked increase in NK and LAK
      cell activity than LAK/IL-2 without LBP. The results indicate that LBP can be
      used as an adjuvant in the biotherapy of cancer.

PMID- 7720498
TI  - [The combined treatment with surgery and chemotherapy: primary approach to small
      cell lung carcinoma (SCLC)].
AB  - Forty cases of small cell lung carcinoma (SCLC) treated with surgical and
      chemotherapeutic combined therapy were reported. There were 28 males and 12
      females in the group, most with history of more than 2 months, ranging in age of
      27-66 years old. Cough, bloody sputum, low fever and chest distress are the main
      clinical manifestation. The small cell undifferentiated carcinoma was confirmed
      by fiberbronchoscope examination and pathology in all patients. Single lobectomy
      was performed in 20 cases, lobectomy of the upper and middle lobe in 9 cases,
      (sleeve resection of the lobarbronchus in 3 cases), and total pneumonectomy in 7
      cases. Two cases were of stage I, 18 were of stage II, and 20 were of stage IIIa.
      Twelve patients received chemotherapy after operation, and 28 patients underwent
      the "chemotherapy-operation-chemotherapy" treatment model. Adriamycin (or CDDP),
      cytoxan, vincristin, and dexomathasone were used for the chemotherapy procedure.
      The 1, 3, 5-year survival rate of chemotherapy after operation and chemotherapy
      operation-chemotherapy group were 70%, 45%, 30.5% and 54%, 30% and 22%,
      respectively. It is demonstrated that the long-term survival rate could be
      elevated in SCLC patients treated with chemotherapy after surgical operation, and
      the chance of operation also could be elevated by preoperative chemotherapy. The
      resection rate was 93% in the preoperative chemotherapy group.

PMID- 7720499
TI  - [Cardiac arrhythmia after lung cancer surgery--an analysis of 140 pneumonectomy
      cases].
AB  - Among 808 surgically resected lung cancer cases at Shanghai Chest Hospital during
      the period of January 1991 to December 1992, 140 of them (17.3%) underwent
      pneumonectomy (47 right, 93 left). In the 140 cases: 124 male, 16 female; aged 27
      74 yrs, pre-operative abnormal EKG was found in 38 cases. Postoperatively,
      arrhythmia occurred in 76 cases, with an incidence of 54.3%. Of the 76
      arrhythmias, atrial fibrillation was seen in 7 patients, atrial premature beats
      in 2, supraventricular tachycardia in 1 and sinus tachycardia in 66. The results
      indicate that cardiac arrhythmia is a common complication after pneumonectomy for
      lung cancer surgery. The major causes of arrhythmia were incisional pain,
      hypovolemia due to blood loss and respiratory insufficiency due to anoxia. The
      perioperative measures to prevent arrhythmia were discussed.

PMID- 7720500
TI  - [Postoperative arrhythmia after resection of esophageal or cardiac carcinoma:
      with analysis of 108 cases].
AB  - Between Sept. 1991 and June 1992, a total of 453 cases with carcinomas of the
      esophagus or gastric cardia underwent surgical resection of cancer. In all
      patients, ECG was continuously monitored for at least 3 days after operation.
      There were 108 cases of postoperative arrhythmias, with an incidence of 23.8%,
      but 32.9% in patients with abnormal preoperative ECG, higher than that with
      normal preoperative ECG (21.9%) (P < 0.05). The postoperative arrhythmia appeared
      more frequently in the gastroesophageal anastomosis above the aortic arch (35.0%)
      than in that below it (16.3%) (P < 0.01). In 87.0% of arrhythmias appeared within
      24 hours after the operation and 72.2% was sinus arrhythmia. The fatal arrhythmia
      was rarely seen. The common causes of postoperative arrhythmia were operative
      trauma and stress, respiratory insufficiency, heart failure, hypovolemia and high
      fever. After treatment in time, arrhythmias disappeared in 4 days. The emphasis
      is to find and get rid of the causes at first, then is the treatment of
      arrhythmia.

PMID- 7720501
TI  - [Prognostic evaluation of lymph node metastasis in thoracic esophageal cancer--an
      analysis of 212 cases].
AB  - The authors studied retrospectively lymph node metastatic status impacts on
      survival of the 212 patients with thoracic esophageal squamous cell carcinoma and
      lymph node metastasis after curative resection. 663 (19.4%) of the total 3419
      lymph nodes examined (an average of 16.1 per patient) were proved to be positive.
      The overall 5-year survival rate was 19.3%. The results showed that no difference
      in survival was observed in relation to the site of the involved lymph node.
      Difference in survival based on the number of metastatic lymph nodes (1 or > or =
      2) and the frequency of positive nodes (< or = 10% or > 10%). The results
      indicate that staging of esophageal cancer should be made according to the
      absolute number and the relative frequency of lymph nodes involved. The
      effectiveness and limitation of extended lymph node dissection in relation to
      prognosis was discussed.

PMID- 7720502
TI  - [A randomized clinical study of preoperative accelerated radiotherapy versus
      routine radiotherapy for late esophageal cancers--an analysis of 177 cases].
AB  - From March 1989 to Oct. 1993, 177 patients with esophageal cancer were treated
      with preoperative radiotherapy. They were randomly divided into two groups:
      preoperative routine radiotherapy (RR) group and accelerated radiotherapy (AR)
      group. In the former group, radiation was given 2 Gy/day, 5 sessions/week with a
      total of 40Gy in 4 wks, while in the AR group, radiation was given 2 Gy/session,
      two sessions/day at an interval of 6-8 hours, 10 sessions/week for 2 weeks with a
      total dose of 40 Gy in 2 weeks. The patients were operated 3-4 weeks after
      radiation. The resectability rate was 95% in AR group, and 90% in RR group. The 1
      , 2-, 3- and 4-year survival rates in AR group were 89%, 85%, 69% and 60%, while
      80%, 65%, 48% and 41% in RR group respectively. The degree of tumor regression
      examined histopathologically was: Grade I in 9%, Grade II in 41% and Grade III in
      50% of AR-treated patients, while in 34%, 39%, 27% of RR-treated patients.
      Periesophageal lymph node metastasis was 13% in AR group, while 24% in RR group.
      The results of AR are better than that of RR indicate that preoperative
      accelerated radiation gave better therapeutic results than routine radiotherapy.

PMID- 7720503
TI  - [A comparative study of therapeutic effects of total versus proximal subtotal
      gastrectomy in adenocarcinoma of the gastric cardia].
AB  - 485 patients with adenocarcinoma of the gastric cardia operated in our hospital.
      283 cases were treated with total gastrectomy, and 202 cases were treated with
      proximal subtotal gastrectomy. The age, sex, clinical stage, size of tumour,
      radicality of surgical resection, lymph node involvement, tumour depth
      penetration and histological type had no significant difference in the two
      groups. Analysis of survival rates failed to demonstrate any significant
      difference between the two types of surgical operation for TNM stage I and II.
      Total gastrectomy resulted in significantly higher survival rate than proximal
      subtotal gastrectomy for stage III. The 3- and 5-year survival rate of TNM stage
      III patients increased by 14.6% and 15.1%, respectively (P < 0.05). Extended
      total gastrectomy was usually applied for stage IV patients without distant
      metastasis. If the neoplasm had spread beyond the confines of extended total
      gastrectomy, in order to eliminate obstruction or bleeding, palliative proximal
      subtotal gastrectomy or total gastrectomy should be considered.

PMID- 7720504
TI  - [Dilatation of anastomotic stricture by Nd:YAG laser beam under endoscopy].
AB  - Anastomotic stricture has become a common complication following surgical
      treatment of upper gastrointestinal cancers. A technique was devised to alleviate
      the stricture with Nd. YAG laser beam under endoscopy. The laser beam was applied
      at 3-4 different points near the anastomotic stoma. The thermal effect of the
      beam would cut the scar tissues in and underneath the mucosa, leading to
      dilatation of the stoma. A total of 48 patients with cancer of the esophagus (n =
      21), gastric cardia (n = 20), body of stomach (n = 6) and gastric stump (n = 1)
      with postoperative anastomotic stricture was so treated. According to the degree
      of dilatation, the result of treatment upon longterm follow-up was good (the
      anastomotic stoma was enlarged more than 6 mm) in 41 (85.4%), fair (the stoma
      enlarged 4-5 mm) in 5 (10.4%) and poor in the remaining 2. Due precautions should
      be made to avoid bleeding and perforation.

PMID- 7720505
TI  - [Hepatic arterial infusion chemotherapy and embolization in the treatment of
      hepatic carcinoma].
AB  - From September 1988 to Dec. 1991, 160 patients, in moderate and advanced stages
      of hepatic carcinoma were treated with hepatic arterial infusion chemotherapy and
      embolization. Among them, 64.3% was of massive type, 26.5% of nodular type and
      9.1% of diffuse infiltrating type. In most of the cases, the tumor was rich in
      blood vasculature. Tumor thrombus in the portal vessels and artero--venous
      fistula were common. The size of tumors were 3cm to 24cm. Most of the tumors
      decreased in size after treatment. In 132 pts followed-up for six to fifty-one
      months the one-year survival rate was 10.8% in the Hepatic Artery Infusion group,
      and 41.9% in the Hepatic Artery Infusion+Hepatic Artery Embolization Iodized Oil
      Gelfoam group. The longest survival period was 51 months after initial Hepatic
      Artery Iodized Oil and Hepatic Artery Embolization. Factors influencing
      therapeutic effects were; (1) stage of the tumor. (2) tumor thrombus in the
      portal vein. (3) methods of Hepatic Artery Infusion and Hepatic Artery
      Embolization. (4) selection of embolic material. (5) development of collateral
      circulation.

PMID- 7720506
TI  - [Treatment of bladder cancer by Nd:YAG laser local irradiation and whole-bladder
      photodynamic therapy with hematoporphyrin derivative].
AB  - Twenty cases with 51 tumor foci of urinary bladder were treated by Nd:YAG laser
      local irradiation plus whole-bladder photodynamic therapy (PDT) with
      hematoporphyrin derivative (HPD). All cases were confirmed by histopathological
      diagnosis. Of the 20 patients, 19 were cured after one treatment (95%) and the
      other patient cured after 2 treatments within 40 days. On follow-up for 3-23
      months, tumor recurrence occurred in 2 cases (10%) about 3-6 months after
      treatment. The results suggest that the PDT effect in destroying bladder tumors
      might be enhanced by Nd:YAG laser while the lesions escaped Nd:YAG laser
      irradiation could be handled by whole-bladder PDT.

PMID- 7720507
TI  - [Assay of DNA content and estrogen receptor status in human breast cancer].
AB  - Cellular DNA content of 72 samples was analyzed by flow cytometry. The results
      showed that 20 benign tumors and 10 normal breast tissue specimens were found to
      be DNA diploidy. 26 (62%) of 42 cases of breast cancer were DNA aneuploidy and
      the remainders were DNA diploidy. The median s-phase cell percentage was
      significantly higher in aneuploid tumors (28%) than diploid tumors (13%) and
      benign tumors (4%). Estrogen receptors were also investigated in 42 breast cancer
      specimens. There were 31 ER positive (74%) cases and 11 negative (26%) cases. The
      aneuploid DNA content was usually associated with lack of estrogen receptors. DNA
      content correlated significantly with age and ER status. The results suggest that
      flow cytometric analysis of cellular DNA content of breast cancer and status of
      estrogen receptors can provide an objective quantitative and reproducible new
      parameter for predicting prognosis of breast cancer.

PMID- 7720508
TI  - [Careful dissection of the pelvic plexus helps alleviate urinary retention
      following radical hysterectomy].
AB  - Radical hysterectomy remains to be the treatment of choice for carcinoma of the
      uterine cervix. As pelvic nerve plexuses are distributed in the operative field,
      damage to the plexuses is likely to occur, which is responsible for the post
      operative atonia of the urinary bladder and urinary retention. To reduce the
      incidence of this postoperative complication, the composition and distribution of
      the pelvic nerve plexuses in relation to the utero-sacral ligament and cardinal
      ligament of the uterus and paravaginal tissues were carefully dissected on 11
      adult female cadavers. Based on the anatomic study, due precautions were made to
      avoid damage to the pelvic nerve plexuses during pelvic dissection for radical
      hysterectomy. As a result, the duration of postoperative urinary retention was
      significantly reduced while the 5- and 10-year survival rates remained unchanged.

PMID- 7720509
TI  - [The clinicopathologic study of histiocytic necrotizing lymphadenitis and the
      differentiated diagnosis with malignant lymphoma--report of 31 cases].
AB  - Histiocytic necrotizing lymphadenitis (HNL) is a kind of rare benign disease,
      predilection to involve the neck of young women, causing enlargement of the lymph
      nodes and usually accompanying by fever and other constitutional symptoms, and a
      unique clinicopathologic course are characteristic of this disease. Because its
      histomorphology has a given spectrum changing, it may lead to misdiagnosis for
      someone who is unfamiliar with it. According to the document records,
      misdiagnostis of HNL could be up to 30%-40%, especially in its early
      proliferative stage. In this 31 cases analysis, the authors systematically
      summarize the clinicopathologic characteristics of this lesion, and focus to
      elucidate the different features between HNL and lymphoma. Although presently it
      is thought that the disease is self-limited, there are two cases with clinical
      manifestations of systemic lupus erythematosus in our series. Possibly, the two
      diseases may have some intrinsic relationships. Long term follow-up of its final
      outcome in these patients is necessary to clarify whether or not HNL is a self
      limiting or progressive disease.

PMID- 7720510
TI  - Metabolism of a candidate 8-aminoquinoline antimalarial agent, WR 238605, by rat
      liver microsomes.
AB  - The in vitro metabolism of the 8-aminoquinoline, 8-(4-amino-1- methylbutylamino
      2,6-dimethoxy-4-methyl-5-(3-trifluromethyl- phenoxy)quinoline (WR 238605), by rat
      liver microsomes was studied. After incubation of WR 238605 with rat liver
      microsomes, the metabolites were isolated either by direct solvent extraction or
      by extraction in the presence of ethyl chloroformate. WR 238605 was extensively
      metabolized to aminophenolic compounds, which underwent air oxidation during the
      isolation process to a mixture of quinones and quinoneimines. Because of the
      instability of the metabolites toward air oxidation, most of them could only be
      isolated as the ethoxycarbonyl derivatives by in situ derivatization with ethyl
      chloroformate. The metabolism of WR 238605 involved the expected metabolic
      pathways, such as O-demethylation, N-dealkylation, N-oxidation, and oxidative
      deamination. In addition, C-hydroxylation involving the 8-aminoalkylamino side
      chain, which was previously unknown for 8-aminoquinoline analogs, was found to be
      an important metabolic pathway for WR 238605. Most of the metabolites retained
      the 5-(m-trifluoromethyl)phenoxy group of WR 238605. Direct and indirect
      supporting evidence for the structure of the metabolites of WR 238605 came from
      the concomitant study of the in vitro metabolism of six other compounds that are
      putative metabolites of WR 238605.

PMID- 7720511
TI  - Identification and quantification of fluorine-containing metabolites of 1-chloro
      2,2,2-trifluoroethane (HCFC133A) in the rat by 19F-NMR spectroscopy.
AB  - 1-Chloro-2,2,2-trifluorethane (HCFC133a) causes a reduction in testis weight and
      germinal epithelial cell atrophy in the rat following exposure by inhalation at
      concentrations of 10,000 ppm and above. Following administration by gavage, an
      increased incidence of Leydig cell tumors of the testis was seen. The metabolism
      of HCFC133a has been investigated in respect to the known toxicity of this
      compound. Male rats were exposed by inhalation to an atmosphere of 50,000 ppm
      HCFC133a for a period of 6 hr. Analysis of urine, collected during the exposure
      period and up to 48 hr following exposure, by 19F-NMR spectroscopy identified
      2,2,2-trifluoroethanol (TFE; and its beta-glucuronide), trifluoroacetaldehyde
      (TFAA; as its hydrate and urea adduct), and trifluoroacetic acid (TFA) as
      fluorine-containing metabolites of HCFC133a. Of the total amount of metabolite
      eliminated in urine, 83% was excreted within 24 hr postdose, establishing a rapid
      elimination of metabolites by this route. TFAA, an established testicular
      toxicant, was the major metabolite accounting for 57% of the total fluorinated
      metabolites eliminated in urine, whereas TFA and TFE accounted for 29% and 14%,
      respectively. The presence of these metabolites in urine is consistent with an
      oxidative route of metabolism of this fluorocarbon.

PMID- 7720512
TI  - Metabolism of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide by isolated
      rat hepatocytes.
AB  - The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is
      nephrotoxic in rats, and hepatic biotransformation appears to be involved in the
      metabolic activation of this compound. NDPS metabolism was therefore investigated
      in vitro using hepatocytes isolated from male Fischer 344 rats. Cells were
      incubated with NDPS at 37 degrees C, and metabolites were analyzed by reversed
      phase HPLC with UV (254 nm) and radiochemical detection. HPLC peaks were
      identified by comparison with synthetic standards. The following oxidative
      metabolites were detected: N-(3,5-dichlorophenyl)-2- hydroxysuccinamic acid (2
      NDHSA); N-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid; N-(3,5-dichlorophenyl)-2
      hydroxysuccinimide; and N-(3,5-dichloro-4-hydroxyphenyl)succinamic acid.
      Formation of the major oxidative product, 2-NDHSA, followed Michaelis-Menten
      kinetics and yielded apparent KM and Vmax values of 1.76 +/- 0.39 mM and 31.01 +/
      3.93 nmol/10(6) cells/hr, respectively. Based on inhibition studies, the
      formation of these products was mediated by cytochrome(s) P450. The hydrolysis
      product N-(3,5-dichlorophenyl)succinamic acid was generated nonenzymatically
      under all incubation conditions. There was no evidence for the formation of
      glucuronide, sulfate, or glutathione conjugates. Cell viability studies showed
      that NDPS and its metabolites were not cytotoxic to the isolated hepatocytes.
      Data demonstrate that isolated hepatocytes can be used to characterize the
      metabolism of NDPS and may be useful in elucidating the role of the liver in NDPS
      induced nephrotoxicity.

PMID- 7720513
TI  - Fate of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET18-OME) in
      malignant cells, normal cells, and isolated and perfused rat liver.
AB  - Ether lipids show high specific cytotoxicity in vitro on a wide variety of
      experimental tumors, but only moderate activity in vivo. One reason for this lack
      of activity in the whole animal might be a high degree of metabolic degradation.
      We therefore studied the biotransformation of 1-O-octadecyl-2-O-methyl-rac
      glycero-3-phosphocholine ([3H]ET18-OMe) labeled in position 9-10 of the 1-alkyl
      chain, in rat plasma and erythrocytes, HL60 and K562 leukemic cells, HT29
      adenocarcinoma cells, and cultured hepatocytes at 37 degrees C, and in a system
      of isolated and perfused rat liver. ET18-OMe and its metabolites were identified
      and quantified after lipid extraction and TLC separation. In tumor cells, 98% of
      ET18-OMe remained almost unmodified in vitro after 24-hr incubation. Plasma and
      erythrocytes from rats metabolized only 4-5% of the original compound in 3 hr. In
      cultured hepatocytes, 35% and 58.3%, respectively, of ET18-OMe was present after
      6 and 24 hr as the metabolites 1-O-alkyl-2-O-methylglycerol (AMG), 1-O-alkyl-2-O
      methylphosphatidic acid (AMPA), and stearyl alcohol (SA) (products of direct
      hydrolysis by phospholipases C and D and alkylhydrolase); phospholipids
      (phosphatidylcholine and phosphatidylethanolamine); and neutral lipids (products
      of secondary metabolism). In perfused rat liver, approximately 15% of the total
      radioactivity incorporated after 3 hr was distributed in metabolites as follows:
      5.9% of AMPA, 5.0% of AMG, and 3.1% of SA. We conclude that the metabolism of
      ET18-OMe in normal tissues occurring through the same enzymes that metabolize
      natural lipids may partly explain the lack of effect in vivo.

PMID- 7720514
TI  - Characterization and formation of the glutathione conjugate of clofibric acid.
AB  - The incubation of 1-O-clofibryl glucuronide (1-O-CAG), a metabolite of
      clofibrate, with glutathione (GSH) resulted in the appearance of a new peak when
      analyzed by HPLC. The use of HPLC coupled to electrospray-MS permitted the
      identification of the peak as S-(p-chlorophenoxy-2-methylpropanoyl)glutathione
      (CA-SG), formed by nucleophilic displacement of the glucuronide moiety from 1-O
      CAG. Conjugate formation was enhanced 8-fold by rat liver glutathione S
      transferases (GSTs). GSH was unreactive with isomers of 1-O-CAG formed by acyl
      migration, indicating that 1-O-CAG itself was the preferred substrate.
      Rearrangement of 1-O-CAG to its isomers in vitro, was found to be decreased in
      the presence of GSH. In vivo studies indicated that, following an intravenous
      infusion of clofibric acid to rats (75 mg/kg), the concentration of CA-SG
      excreted in bile over 4 hr, was approximately 0.1% of the concurrent CAG
      concentrations. Although these results indicate a minor role for GST-catalyzed
      reactions in clofibrate metabolism in vivo, they do define 1-O-acyl-linked
      glucuronides as a new class of substrates for GSTs.

PMID- 7720515
TI  - Metabolism of [14C]- and [35S]S-(1,2-dichlorovinyl)-L-cysteine in the male
      Fischer 344 rat.
AB  - The metabolic fate, tissue distribution, and elimination profile of [35S]- and
      [cysteine-U-14C]S-(1,2-dichlorovinyl)-L-cysteine (DCVC)--given either
      intravenously or intraperitoneally to male Fischer 344 rats--was investigated.
      Blood samples were collected periodically from 5 min to 96 hr after
      administration. More than 99% of the DCVC was cleared from plasma within 2.5 hr
      after either intravenous or intraperitoneal injection. The initial half-lives of
      both [35S]- and [14C]DCVC were 2.0 and 2.8 hr, respectively, and the mercapturate
      S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine was detected in plasma within 5 min of
      giving DCVC. The major plasma metabolite detected after giving [35S]DCVC was
      inorganic sulfate, and S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine and pyruvate
      were also detected in plasma after giving [14C]DCVC. S-(1,2-Dichlorovinyl)-N
      acetyl-L-cysteine was the major urinary metabolite detected after giving
      [14C]DCVC, and inorganic sulfate was excreted in the urine after giving
      [35S]DCVC. Administration of the cysteine conjugate beta-lyase inhibitor
      aminooxyacetic acid led to a significant increase in the urinary excretion of
      radioactivity, mostly in the form of the mercapturate. The kidney contained the
      highest amount of radioactivity after administration of [35S]DCVC. In addition,
      similar amounts of radioactivity were present in brain, heart, kidney, and liver
      after administration of [14C]DCVC, but the 14C content of the liver was decreased
      in aminooxyacetic acid-treated rats. This study shows that DCVC is rapidly
      metabolized to inorganic sulfate and S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine,
      which are eliminated in the urine.

PMID- 7720516
TI  - Metabolism of [14C]naphthalene in the B6C3F1 murine isolated perfused liver.
AB  - Naphthalene (NA) is metabolized by pulmonary and hepatic tissues to epoxides,
      quinones, and their related phase II metabolites. To delineate specific liver
      metabolites, metabolism was studied in B6C3F1 mouse liver perfused with 5 and 10
      mumol/hr [14C]NA. Liver metabolites were compared with urinary metabolites from
      mice exposed to an equivalent total dose of NA (50 mg/kg ip) to ascertain
      interorgan and extrahepatic transformation in vivo. Metabolites were separated
      into pools via hydrophobic columns under neutral (pool I) and acid (pool II)
      conditions. Pool I contained the majority of [14C] in perfusate and urine. In
      perfusate, high levels of sulfate conjugates of naphthol and dihydroxynaphthalene
      were found along with dihydrodiol and glucuronic acid conjugates. In the urine,
      dihydrodiol was the most abundant metabolite. A novel N-acetylated glutathione
      conjugate was a constituent of pool II of both perfusate and urine. Additional
      metabolites identified in urine were N-acetylcysteine conjugate of dihydrodiol
      epoxide, mercaptolactic acid conjugate of naphthalene oxide (NO), and
      diglucuronide and sulfate/glucuronide conjugates of dihydroxynaphthalene.
      Mercapturic acid conjugates of NO were not observed in either perfusate or urine;
      this finding highlights metabolic differences between strains. Differential
      covalent binding occurred in cellular fractions, with the highest binding
      occurring in microsomes and mitochondria. These metabolites indicate that
      interorgan metabolism plays a role in the disposition of NA in vivo.

PMID- 7720517
TI  - Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver.
AB  - Budesonide is a synthetic glucocorticosteroid that is commonly used in topical
      treatment of asthma and rhinitis. The main metabolites formed from budesonide in
      human liver microsomes have been identified as 16 alpha-hydroxyprednisolone and 6
      beta-hydroxy-budesonide. Although it is apparent that the cytochrome P450 (CYP)
      system is involved, the actual subfamily has not been identified. In attempts to
      do this, budesonide was incubated with microsomes from ten different human liver
      samples where various CYP activities had been rank ordered. We found a strong
      correlation between formation of the two main metabolites and testosterone 6 beta
      hydroxylation (correlation 0.98 and 0.95), a marker for CYP3A. When budesonide
      (10 microM) was incubated with human liver microsomes in the presence of
      compounds known to interact with different isoforms or subfamilies of CYP,
      ketoconazole was found to be the strongest inhibitor of budesonide metabolism
      (IC50: approximately 0.1 microM) followed by troleandomycin (IC50: approximately
      1 microM), erythromycin, and cyclosporin, all substances known to interact with
      CYP3A isoenzymes. Substances known to interact with CYP2C (sulfaphenazole,
      mephenytoin, and tolbutamide) and with CYP2D6 (bufuralol and quinidine) did not
      specifically inhibit the metabolism of budesonide. In addition, formation of the
      budesonide metabolites (16 alpha-hydroxyprednisolone and 6 beta
      hydroxybudesonide) was inhibited by antibodies against the CYP3A subfamily, but
      not by antibodies against the CYP1A subfamily or control immunoglobulin G. We
      conclude that the formation of 16 alpha-hydroxyprednisolone and 6 beta
      hydroxybudesonide from budesonide is catalyzed by isoenzymes within the CYP3A
      subfamily.

PMID- 7720518
TI  - Nicotine and cotinine accumulation in pigmented and unpigmented rat hair.
AB  - This study was performed to assess the contribution of systemic and external
      uptake to nicotine accumulation in hair. The systemic nicotine uptake in hair was
      determined in pigmented rats (Brown Norway) and albino rats (Sprague-Dawley)
      after subcutaneous administration of 3 doses of nicotine with osmotic minipumps
      [5, 10, and 20 mg/(kg x day) for 3 weeks], the highest dose also following
      metabolic enzyme induction. The external nicotine uptake was determined in cut
      hair of both strains after exposure to room-aged cigarette sidestream smoke, a
      surrogate for environmental tobacco smoke (nicotine concentration: 5
      micrograms/liter for 1, 2, and 3 weeks). Nicotine and its metabolite cotinine
      were determined using capillary GC after complete alkaline digestion of the hair
      sample and solvent extraction. Systemic uptake: Nicotine and cotinine
      concentrations in hair were dose-dependent and correlated with plasma
      concentrations. The nicotine concentration was approximately 20 times higher in
      pigmented than in unpigmented hair. The cotinine concentration was approximately
      10 times lower than the nicotine concentration in pigmented hair. After enzyme
      induction before administration, nicotine and cotinine concentrations in hair
      were significantly reduced in parallel to the reduced plasma concentrations,
      showing the influence of metabolism. External uptake: Nicotine was found in the
      hair of both strains, the concentration in pigmented hair being a factor of 1.5
      higher than in unpigmented hair. Thus, hair pigmentation had a major influence on
      systemic uptake in hair and a minor influence on external uptake in
      hair.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720519
TI  - Stereoselective glucuronidation of zileuton isomers by human hepatic microsomes.
AB  - The glucuronidation of the R-isomer and S-isomer of the 5-lipoxygenase inhibitor
      zileuton was examined using human hepatic microsomes. The glucuronidation of both
      isomers followed Michaelis-Menten kinetics, but glucuronidation rates were
      between 3.6- and 4.3-fold greater for the S-isomer. The apparent Km's (microM)
      for the R-isomer (392.9 +/- 35.9) and S-isomer (322.5 +/- 22.0) glucuronidation
      were similar, whereas the apparent Vmax (nmol/mg protein/min) was 3.4-fold
      greater for the S-isomer (5.2 +/- 0.7). In combination, each isomer competitively
      inhibited the glucuronidation of its antipode. The average Ki (microM) determined
      for S-isomer inhibition of R-isomer glucuronidation (197.8 +/- 61.3) was 2.4-fold
      lower than the Ki for the reciprocal interaction. These data indicate that the
      glucuronidation of the zileuton isomers in human hepatic microsomes is
      stereoselective. This stereoselective glucuronidation may be the basis for the
      more rapid clearance of the S-isomer observed in humans receiving zileuton.

PMID- 7720520
TI  - Cytochrome P450 inhibitors. Evaluation of specificities in the in vitrometabolism
      of therapeutic agents by human liver microsomes.
AB  - Identifying selective inhibitors of cytochrome P450 isoforms is a useful tool in
      defining the role of individual cytochrome P450s in the metabolism process. In
      this study, nine chemical inhibitors were selected based on literature data and
      were examined for their specificity toward cytochrome P450-mediated reactions in
      human liver microsomes. Furafylline was a potent, mechanism-based inhibitor for
      CYP1A2-mediated phenacetin O-deethylation. The probes sulfaphenazole (CYP2C9) and
      quinidine (CYP2D6) selectively inhibited tolbutamide methylhydroxylation and
      bufuralol 1'-hydroxylation, respectively. Additionally, the CYP2E1-catalyzed
      chlorzoxazone 6-hydroxylation was significantly inhibited by
      diethyldithiocarbamate. Of the CYP3A4 inhibitor probes used, troleandomycin
      proved to be the most specific for testosterone 6 beta-hydroxylation.

PMID- 7720521
TI  - Side-chain hydroxylation in the metabolism of 8-aminoquinoline antiparasitic
      agents.
AB  - Primaquine, 8-(4-amino-1-methylbutylamino)-6-methoxyquinoline, is an antimalarial
      8-aminoquinoline derivative. Although it has been in use since 1952, its
      metabolism has not been clearly defined. This is due to the instability of the
      expected aminophenol metabolites and their amphoteric nature, which makes their
      isolation difficult. Recent studies on the metabolism of WR 238605, a new
      primaquine analog, has shown that these problems may be solved by extracting the
      metabolites in the presence of ethyl chloroformate. Subsequent identification of
      the ethoxycarbonyl derivatives of the metabolites has made it possible to define
      the in vitro metabolism of primaquine. The primary metabolic pathways of
      primaquine involved hydroxylation of the phenyl ring of the quinoline nucleus and
      C-hydroxylation of the 3'-position of the 8-aminoalkylamino side chain. Ring
      hydroxylation of primaquine gives rise to 5-hydroxyprimaquine, which on
      demethylation produces 5-hydroxy-6-demethylprimaquine. Side-chain hydroxylation
      of primaquine gives rise to 3'-hydroxyprimaquine, which also undergoes O
      demethylation to 3'-hydroxy-6-demethylprimaquine. 6-Demethylprimaquine, a
      putative metabolite of primaquine, also underwent metabolism involving 3'
      hydroxylation of the side chain. WR 6026, 8-(6-diethylaminohexylamino)-6-methoxy
      4-methylquinoline, is an antileishmanial 8-aminoquinoline derivative. The in
      vitro metabolism of WR 6026 also results in the formation of side chain
      oxygenated metabolites. The present results, together with previous observations
      on the metabolism of WR 238605 and closely related primaquine analog, suggest
      that side-chain oxygenation is an important metabolic pathway of antiparasitic 8
      aminoquinoline compounds in general.

PMID- 7720522
TI  - Ocular absorption, distribution, and systemic absorption of a novel antiglaucoma
      medication, prostaglandin derivative, in male white rabbits.
AB  - A prostaglandin derivative, (5Z,9 alpha,11 alpha,13E)-9,11-dihydroxyprosta- 5,13
      dienoic acid sodium salt (S-1033), that lowers intraocular pressure with little
      adverse effect, may have clinical value in the treatment of glaucoma. After
      [14C]S-1033 (0.2% solution) was instilled into the eye of a white rabbit,
      radioactivity and S-1033 appeared in systemic plasma so rapidly (tmax, 5 min) and
      S-1033 was eliminated very rapidly with half-lives of 2.8 and 11.0 min at alpha-
      and beta-phases, respectively. The metabolite, M-1, [1R-[1 alpha,2 beta-(1E),3
      alpha,5 alpha]]-3,5-dihydroxy-2-(1- octenyl)-cyclopentanepropanoic acid (tetranor
      S-1033), appeared in plasma very rapidly (tmax, 5 min), suggesting that a fast
      metabolism was a major factor in the rapid elimination of S-1033 from plasma. The
      values for the ratios of the area under the curve of ocular instillation to
      intravenous administration for radioactivity and S-1033 were 1.01 and 0.52,
      respectively, indicating that more than half of the S-1033 instilled was
      transported into the systemic circulation. To clarify the contributing pathway of
      the massive and rapid systemic absorption of S-1033 after topical dosing, plasma
      levels of S-1033 were investigated after instillation to rabbits in which the
      nasolacrimal ducts were occluded. Plasma concentrations of S-1033 were slightly
      higher than those in intact rabbits, suggesting that conjunctiva would be as
      important as nasal mucosae for the systemic absorption under the physiological
      condition. As for the intraocular distribution, the highest levels of
      radioactivity were found in the cornea, conjunctiva, and anterior
      sclera.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720523
TI  - Infection (Actinobacillus pleuropneumoniae)-mediated suppression of oxidative
      hepatic drug metabolism and cytochrome P4503A mRNA levels in pigs.
AB  - The effect of Actinobacillus pleuropneumoniae infection, a well-characterized pig
      infection model, on both phase I (oxidative) and phase II (conjugative)
      microsomal enzyme activities was investigated in castrated male conventional
      pigs. A. pleuropneumoniae infection resulted after 24 hr in a significant
      suppression of 33% or more of all oxidative enzyme activities determined. After
      40 hr, the activities were still suppressed, but did not differ from the results
      after 24 hr. On the contrary, all glucuronosyltransferase activities measured
      were not affected by A. pleuropneumoniae infection after both 24 and 40 hr. To
      elucidate further the mechanism of the suppression of oxidative enzyme
      activities, analysis of mRNA were conducted by dot-blot analysis using a human
      cytochrome P4503A4 cDNA probe. The results indicated that A. pleuropneumoniae
      infection suppressed oxidative enzyme activities. The reduction in cytochrome
      P4503A activity, specific for 6 beta-hydroxylation of testosterone is at a
      pretranslational level as measured by a decrease in the amount of mRNA.

PMID- 7720524
TI  - Biosynthesis of S-(2-chloro-1,1,2-trifluoroethyl)glutathione in rat and human
      hepatocytes and in Hep G2 cells.
AB  - Chlorotrifluoroethene is nephrotoxic in rats, and glutathione S-transferase
      catalyzed S-(2-chloro-1,1,2-trifluorethyl)glutathione (CTFG) formation is the
      initial step in its bioactivation. CTFG biosynthesis and the activities of
      cytosolic and microsomal glutathione S-transferases were measured in rat and
      human hepatocytes and in human hepatoma-derived Hep G2 cells. Hepatocytes of > or
      = 88% viability were obtained from rat or human liver slices by collagenase or
      collagenase+dispase digestion, respectively. Hep G2 cells were grown in modified
      Earle's medium supplemented with 10% (v/v) fetal calf serum. Cells and
      subcellular fractions were exposed to chlorotrifluoroethene, and CTFG formation
      was quantified by HPLC. Both human liver and Hep G2 cell subcellular fractions
      catalyzed CTFG formation, and human and rat microsomal fractions exhibited higher
      specific activities than cytosolic fractions with chlorotrifluoroethene as the
      substrate. Time-dependent formation of CTFG was observed in all cell
      preparations. The presence of microsomal glutathione S-transferase was
      demonstrated by Western blotting with antimicrosomal glutathione S-transferase
      antibodies in rat and human liver tissue and in Hep G2 cells. Cytosolic and
      microsomal glutathione S-transferase activities were lower in Hep G2 cells than
      in rat and human liver tissues. These results demonstrate that human hepatocytes
      and Hep G2 cells are competent to synthesize CTFG and that Hep G2 cells may
      provide a useful model for studying human liver-catalyzed glutathione S-conjugate
      formation.

PMID- 7720525
TI  - Pharmacokinetics and organ clearance of a 3'-biotinylated, internally [32P]
      labeled phosphodiester oligodeoxynucleotide coupled to a neutral
      avidin/monoclonal antibody conjugate.
AB  - The pharmacokinetics and organ uptake of a 3'-biotinylated, [32P] internally
      labeled 36-mer phosphodiester oligodeoxynucleotide (PO-ODN) were measured after
      intravenous injection in the anesthetized adult rat. The PO-ODN was antisense to
      the tat gene of the human immunodeficiency virus, and was 3'-biotinylated to a)
      protect against serum and tissue 3'-exonuclease activity, and b) facilitate
      coupling to a neutral avidin-based transcellular drug delivery vector. The latter
      was comprised of a covalent conjugate of neutral avidin (NLA) and the OX26 murine
      monoclonal antibody to the rat transferrin receptor. The PO-ODN was internally
      labeled at the 21-nucleotide position to prevent rapid hydrolysis [32P] label by
      serum and tissue 5'-phosphatases. The uptake of the 3'-bio-[32P21]PO-ODN by
      brain, heart, kidney, lung, and liver was measured. The studies show that the
      unconjugated 3'-bio-[32P21]PO-ODN was rapidly removed from plasma, with a mean
      residence time of 22 +/- 1 min and a systemic clearance of 9.2 +/- 0.5 ml/min/kg.
      Large amounts of [32P] radioactivity were recovered in the urine following the
      injection of the PO-ODN, and when this fraction was included in the calculation
      of the renal clearance parameter, the renal clearance was 20-fold higher,
      indicating the principal site of organ clearance of the unconjugated PO-ODN was
      the kidney. Conjugation of the 3'-bio-PO-ODN to the NLA-OX26 vector reduced the
      systemic clearance 50%, owing to a > 10-fold reduction in renal clearance.
      Following conjugation of the 3'-bio-PO-ODN to the NLA-OX26 vector, the major
      clearance organ was the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720526
TI  - Isoflurane-chlorodifluoroethene interaction in human liver microsomes. Role of
      cytochrome P4502B6 in potentiation of haloethene metabolism.
AB  - Short-chain saturated halocarbons, including isoflurane and the
      chlorofluorocarbon substitute HCFC-123, can strongly potentiate the cytochrome
      P450-dependent oxidation of gaseous haloethenes, such as 2-chloro-1,1
      difluoroethene (CDE) and vinyl chloride, in vivo and in vitro. P450 isozyme
      specificity in this effect is suggested by the fact that the interaction is
      pronounced in microsomes from rats treated with phenobarbital, but does not occur
      in microsomes of isoniazid- or beta-naphthoflavone-treated animals. We examined
      the effect of isoflurane on CDE defluorination in liver microsomes from 10 human
      organ donors to determine whether saturated halocarbon/haloethene interactions
      also occur in humans and, if so, to determine the cytochromes P450 involved.
      Three of the samples exhibited isoflurane-stimulated increases (24, 32, and 41%)
      in CDE defluorination; isoflurane either inhibited or had no effect on CDE
      metabolism in the other seven samples. Two samples in which isoflurane
      potentiated CDE metabolism to the greatest rates had higher coumarin 7
      hydroxylase (indicative of CYP2A6), 7-ethoxycoumarin O-deethylase (CYP2B6), and
      nifedipine oxidase (CYP3A4) activities than the other eight samples. However, all
      10 subjects had similar rates of phenacetin O-deethylation (CYP1A2) and
      chlorzoxazone 6-hydroxylation (CYP2E1). In microsomes from cells transfected with
      cDNAs coding for individual human P450s, CDE metabolism by CYP2B6 was stimulated
      (216%) by isoflurane, whereas isoflurane did not stimulate CDE metabolism by
      human CYP2A6, CYP3A4, CYP2D6, or CYP2E1. Isoflurane highly increased CDE
      defluorination in purified rat CYP2B1 (470%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720527
TI  - In vitro and in vivo biotransformations of the naphthalenic lignan lactone 5
      lipoxygenase inhibitor, L-702,539.
AB  - It has been reported previously that the tetrahydropyranyl naphthtalenic lignan
      lactone L-702,539 is a potent nonredox, 5-lipoxygenase inhibitor that has the
      advantage that it can be dosed either as the lactone or as the corresponding
      nonactive hydroxy acid L-702,618 (opened lactone). Studies with hepatic
      microsomes from the rat, rhesus monkey, and human were undertaken in a phosphate
      buffer and suggested that the closure of the hydroxy acid L-702,618 to the
      lactone L-702,539 was an enzymatic process. The incubation of L-702,539 under
      oxidative conditions with these specific hepatic microsomes resulted in the
      formation of three significant metabolites (> 0.4 nmol/mg protein/hr) as
      determined by HPLC with UV detection. These metabolites were isolated from large
      microsomal incubations and were characterized by MS and NMR spectroscopy. Data
      showed that the lactone and tetrahydropyran portions of the molecule were both
      susceptible to hydroxylation, and the hydroxylated tetrahydropyran was further
      oxidized to the hydroxy acid. Analysis of plasma samples obtained from rat and
      rhesus monkeys following L-702,618 administration indicated that the in vivo
      metabolic pathway was similar to the one observed in vitro using hepatic
      microsomes. Studies conducted with microsomes from genetically engineered human
      cell lines expressing individual cytochrome P450s indicated that the isozyme
      responsible for the metabolism at the tetrahydropyran ring, was P4503A4. These
      findings were supported by studies conducted in human microsomes using an
      inhibitory P4503A4 antibody and troleandomycin, which is a potent P4503A
      inhibitor.

PMID- 7720528
TI  - Xenopus laevis: a model system for the study of embryonic retinoid metabolism. I.
      Embryonic metabolism of 9-cis- and all-trans-retinals and retinols to their
      corresponding acid forms.
AB  - Recently, the temporal and spatial distribution patterns of two established,
      endogenous retinoid receptor ligands, 9-cis-retinoic acid and all-trans-retinoic
      acid and various precursor retinoids were described in Xenopus embryos during
      early development (Creech Kraft et al., Proc. Natl. Acad. Sci. U.S.A. 1994;
      Biochem. J. 1994). Each of these two receptor ligands is a metabolite of vitamin
      A (all-trans-retinol), and each is also a potent dysmorphogen in Xenopus embryos
      as well as in embryos of several other vertebrate species. This study
      demonstrates early embryonic metabolism of exogenous all-trans-retinol, 9-cis
      retinol, all-trans-retinal, and 9-cis-retinal to 9-cis-retinoic acid, all-trans
      retinoic acid, and other metabolites in Xenopus embryos during neurulation, a
      specific stage of development that spans a time period of approximately 8 hr. Our
      results demonstrate that the Xenopus embryo provides a suitable model system for
      studying the embryonic bioconversion of retinoids and dysmorphogenic effects
      within a single time window of development.

PMID- 7720529
TI  - Xenopus laevis: a model system for the study of embryonic retinoid metabolism.
      II. Embryonic metabolism of all-trans-3,4-didehydroretinol to all-trans-3,4
      didehydroretinoic acid.
AB  - This study demonstrates early embryonic metabolism of exogenous all-trans-3,4
      didehydroretinol (vitamin A2) to all-trans-3,4-didehydroretinal and to all-trans
      3,4-didehydroretinoic acid in Xenopus embryos during neurulation. The latter
      metabolite was recently shown to bind with high affinity and to activate various
      retinoic acid receptors. Embryos treated with all-trans-3,4-didehydroretinol
      during early or late gastrulation exhibited abnormalities along the
      anteroposterior axis. The abnormalities were primarily in the posterior regions
      of the embryo, with only minor defects anteriorally. Eye malformations, typical
      for early exposure to 9-cis- and all-trans-retinols and retinals (companion
      paper), were not observed. We also present evidence that all-trans-3,4
      didehydroretinoic acid is present endogenously during early neurulation and is
      evenly distributed along the anteroposterior axis. After treatment with all-trans
      3,4-didehydroretinol, embryonic levels of all-trans-3,4-didehydroretinoic acid
      exceeded endogenous levels of this metabolite during early and late neurulation.
      We hypothesize that the dysmorphogenic effects produced by treatment of Xenopus
      embryos with the alcohol precursor, all-trans-3,4-didehydroretinol, are the
      result of its embryonic conversion to its corresponding acid ligand.

PMID- 7720530
TI  - Pharmacokinetics and bioavailability of topiramate in the beagle dog.
AB  - Male and female beagle dogs showed rapid absorption following oral administration
      of single oral gavage (40 mg/kg) and single or multiple (15 days) oral capsule
      (10, 40, and 150 mg/kg) doses of the novel anticonvulsant drug, topiramate, with
      the peak plasma concentration (Cmax) occurring between 0.6 and 3.8 hr. The
      absolute bioavailability of an oral dose of topiramate was estimated to be in the
      range of 27-59%, depending on the formulation. The mean topiramate Cmax values
      increased in a dose-proportional manner for both single (9.2-137.7 micrograms/ml)
      and multiple (10.3-145.2 micrograms/ml) oral capsule administrations, whereas the
      corresponding area under the plasma concentration vs. time curve (AUC) values
      increased in a dose-related but nonproportional manner for both single (51-1131
      micrograms.hr/ml) and multiple (54-858 micrograms.hr/ml) doses. Over the 10-150
      mg/kg dosing range, oral plasma clearance and terminal half-life values were
      found to be 2.4-3.6 ml/min/kg and 2.6-3.7 hr following a single oral
      administration, and 3.0-4.2 ml/min/kg and 2.0-3.8 hr after multiple doses. There
      were no significant differences between the pharmacokinetic parameters calculated
      following the first and fifteenth daily doses of topiramate at the 10 and 40
      mg/kg levels, indicating that there was no accumulation and no autoinduction or
      inhibition of enzymes that metabolize topiramate resulting from multiple dosing
      at these levels. A slight (24%) decrease in AUC was observed at the 150 mg/kg
      level after the fifteenth daily dose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720531
TI  - Biotransformation of CI-937 in primary cultures of rat hepatocytes. Formation of
      glutathione conjugates.
AB  - The anticancer drug 7,10-dihydroxy-2-[2-[(2-hydroxyethyl)amino]- ethyl]-5-[[2
      (methylamino)ethyl]amino]anthra[1,9-c,d]pyrazole- 6(2H)-one dihydrochloride (CI
      937) is 1 of 3 anthrapyrazole derivatives chosen for phase I and phase II
      clinical trials. Although the chemical structure of CI-937 signals a contribution
      of redox reactions in the pharmacology of the drug, a study concerning the
      biotransformation of CI-937 is still missing. Incubations of primary cultures of
      rat hepatocytes with CI-937 result in the formation of three glutathione
      conjugates and a glucuronic acid conjugate. The structures of the glutathione
      conjugates have been established by reference synthesis with activated
      horseradish peroxidase and HPLC-MS-MS and two-dimensional NMR measurements. The
      glucuronic acid derivative of CI-937 has been identified by MS. The formation of
      the glutathione conjugates in cells establishes the ability of the drug to form
      covalent bonding to intracellular nucleophilic targets. The conjugation with
      glutathione has been rationalized by oxidative activation of CI-937, yielding an
      electrophilic intermediate that finally reacts with glutathione.

PMID- 7720532
TI  - [Doppler echocardiographic analysis of diastolic function in dilatative
      cardiomyopathy for the evaluation of its progression and prognosis].
AB  - The relationship between left-ventricular diastolic function and the course of
      the disease was investigated in a prospective study of 61 patients (44 men, 17
      women; median age 51 [26-74] years) with dilated cardiomyopathy. The diastolic
      function was measured by recording the transmitral Doppler flow profile. During a
      follow-up period of 33 +/- 23 months, 15 patients died (twelve of progressive
      heart failure, three suddenly without previous heart failure). Cardiac
      transplantation was performed in four patients. The overall 1-year mortality rate
      was 14%. A "restrictive" Doppler echocardiographic filling pattern with a steep
      early-diastolic maximum and a small atrial filling component predominated in the
      patients who died from progressive heart failure or had a cardiac transplantation
      because of it. The deceleration of the early diastolic velocity maximum was
      clearly shorter than in the survivors (111 +/- 32 ms vs 194 +/- 62 ms; P <
      0.001). In a Cox proportional hazard model the deceleration time was the best
      prognosticator, followed by the end diastolic left-ventricular diameter (LVD).
      The group of patients with a short deceleration time (< or = 140 ms) had a
      significantly higher 1-year mortality rate (28% [confidence interval 9-47%]) than
      those in whom it was longer (3% [0-11%]; P < 0.0001). Taking into account LVD it
      proved possible to identify a prognostically especially unfavourable group with a
      1-year mortality rate of 53% (26-80%), characterized by a LVD > 70 mm and a
      deceleration time < or = 140 ms. Repeated echocardiography in 26 survivors and
      nine patients who died later or had been operated on showed that the deceleration
      time did not change significantly in the course of the disease. On the other
      hand, the systolic function, as measured by the echocardiographically determined
      shortening fraction, improved in the survivors (from 0.18 +/- 0.07 to 0.22 +/-
      0.08; P < 0.05), but not in those who later on died.

PMID- 7720533
TI  - [Therapy of an abdominal aortic aneurysm using transfemoral endovascular
      implantation of a bifurcation prosthesis].
AB  - Transfemoral intraluminal placement of a woven-dacron bifurcation prosthesis was
      undertaken to bridge an infrarenal aortic aneurysm (4.6 cm diameter) in a 65-year
      old man with chronic coronary heart disease. The Chuter-Gianturco introducing
      system was used via the right femoral artery to anchor the prosthesis immediately
      below the origins of the renal arteries. After fixing the right branch of the
      prosthesis the left one was secured via the left femoral artery. No leakage was
      demonstrated on the 7th post-operative day and the aneurysm was satisfactorily
      bridged. Regular follow-up tests showed a normal circulation. Spiral computed
      tomography after 18 months confirmed complete thrombosis of the aneurysm.--This
      case shows that the described method is a promising alternative in the treatment
      of abdominal aneurysm.

PMID- 7720534
TI  - [The "nutcracker esophagus." An as yet seldom noticed disease].

PMID- 7720535
TI  - [Bones and their diseases. I. Bone remodeling].

PMID- 7720536
TI  - [Molecular genetics of cardiovascular diseases].

PMID- 7720537
TI  - [Bioavailability of furosemide in right cardiac insufficiency].

PMID- 7720538
TI  - [Physiopathology of myocardial blood flow].

PMID- 7720539
TI  - ["Troponin T rapid test"--the new dimension in the diagnosis of myocardial
      infarction?].

PMID- 7720540
TI  - [Life-threatening heart rhythm disorders during quinine medication].

PMID- 7720541
TI  - [GISSI-III study].

PMID- 7720542
TI  - [Adjuvant therapy after curative resection of rectal carcinoma].

PMID- 7720543
TI  - [Possibilities of contagion of gastrointestinal and lung nematode infections of
      fallow deer for cattle, sheep and goats raised in the same fenced area as fallow
      deer].
AB  - Cattle as well as sheep and goats may be infected with parasitic nematodes of
      fallow deer under natural conditions, but heavy infections do not occur. Most
      nematode species were recorded in goats, cattle harboured the fewest number of
      species. The specific abomasal parasites of fallow deer (Spiculopteragia
      asymmetrica, Apteragia quadrispiculata, Skrjabinagia ryjikovi, Ostertagia
      drozdzi) were only seen in goats in greater number while both cattle and sheep
      were only poor susceptible. Capillaria bovis was observed in goats and sheep,
      cattle and sheep harboured Cooperia pectinata and Nematodirus roscidus.
      Oesophagostomum venulosum was recorded in cattle, sheep and goats.
      Oesophagostomum sikae was recovered only from fallow deer. Dictyocaulus eckerti
      was seen in fallow deer and in one cattle.

PMID- 7720544
TI  - [Effect of glucocorticosteroids on the liver function of fasting sheep].
AB  - During a five-day fasting period prednisolone (30 mg/d) reduced strongly as a
      result of induced hyperglycemia and hyperinsulinaemia the rise of FFA and
      bilirubin in six nonpregnant ewes in contrast to six control animals. The liver
      fat content remained in treated ewes within the physiological range, but in
      control animals the fat concentration increased to 300 g/kg. beta-OH-butyrate was
      only a little influenced. Harmful effects on the liver function in prednisolone
      treated ewes could not be observed. Plasma cortisol concentration contradicted a
      depression of endogenous cortisol secretion.

PMID- 7720545
TI  - [Clinical studies of kidney function in sheep. I. Methods and reference values of
      healthy animals].
AB  - Investigations of renal function have been done on the basis of renal clearance
      (Clr) and excretion (E) of endogenous creatinine in health sheep of different
      body weight (89 female, 19 male). Creatinine-E was negatively correlated with
      body weight in female sheep, it can be calculated from body weight. The
      Creatinine-Clr in ewes ranged from 1.1 to 2.3 ml/min/kg and was highly correlated
      with inulin-Clr (r = 0.88, p < 0.001). Fractional excretion (FE) of creatinine,
      determined by inulin-Clr was 118%. That demonstrate a tubular secretion of 15% of
      the total excretion. Therefore the creatinine-Clr may be considered
      representative enough for the glomerular filtration rate (GFR). Urea-FE was 24
      50%, and urea-Clr about 50% of the inulin-Clr, that points to a high tubular urea
      absorption (50-75%). For that reason urea is not appropriate for the
      characterization of kidney functions. Water, sodium, glucose, L-lactate and 3-OH
      hydroxybutyrate were absorbed in the renal tubules nearly completely (FE < 2%).
      So they are suitable as endogenous markers for insufficient tubular absorption.
      Calcium, phosphate, magnesium and potassium are reabsorbed incompletely,
      depending on the supply of these substances (FE 0-15%, potassium 5-100%). A
      method for clinical determination of kidney function by measurement of
      concentrations of metabolites and electrolytes in blood plasma and spontaneous
      urine is described and evaluated. The method is based on the calculation of the
      creatinine-excretion, depending on sex and body weight, and especially allows the
      examination of male and sick animals without quantitative sampling of
      urine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720546
TI  - [Clinical studies of kidney function in sheep. II. Effect of pregnancy, lactation
      and feed restriction and metabolic diseases on kidney function].
AB  - Investigations of renal function have been done in healthy ewes in different
      stages of reproduction, and after food restriction, as well as in ewes sick with
      ketosis, hypocalcemia, rumen acidosis and different nephropathies. The
      determination was based on the estimated weight dependent endogenous creatinine
      excretion (E). A reference population of 56 healthy non or early pregnant ewes
      (before day 120 of pregnancy) was used as control. Late pregnancy (121.-149. day,
      n = 14) and lactation (n = 14) lead to higher renal creatinine-clearance
      (approximately GFR). Food restriction in all stages of pregnancy was followed by
      lower plasma concentrations of potassium, calcium, magnesium and glucose, and a
      reduced fractional excretion of potassium, calcium and magnesium. Pregnancy and
      especially food restriction caused a marked rise of the 3-OH-hydroxybutyrate
      values in the plasma and a significant acetonuria. After withdrawal of feed in
      lactating sheep, in opposition to pregnant sheep, the plasma values of phosphate
      were higher. In ketotic sheep (n = 43) a failure of renal function could not be
      demonstrated, the pronounced acetonuria could be explained by acetonemia. In
      hypocalcemia (n = 23) disturbance of creatinine-clearance and tubular
      reabsorption of sodium, potassium, glucose and 3-OH-butyrate could be seen.
      Glucosuria and acetonuria were caused by increased plasma concentrations and
      reduced tubular reabsorption. In rumen acidosis (n = 10) disturbances of low
      degree of GFR and reabsorption could be seen, glucosuria was mainly due to
      hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720547
TI  - [Birth difficulties in sheep and goats--evaluation of patient outcome from seven
      lambing periods in an obstetrical clinic].
AB  - The incidence of parturition difficulties from 239 sheep and 21 does from the
      last seven lambing periods was recorded at a clinic for obstetrics. Without
      exception the does were housed under extensive conditions by hobby-breeders. The
      sheep also originated predominantly from hobby-breeders and in a smaller amount
      from professional breeders, both practising extensive housing. The incidence of
      manual deliveries (m.d.) in both species was lower (39.3% in sheep; 42.8% in
      does) than that of caesarean sections (c.s; 57.3% in sheep; 47.7% in does). In a
      small amount the obstetrics were solved via fetotomy. The practical proceedings
      concerning the different methods of therapies including analgesia, surgical
      approaches and postoperative treatments are described. In sheep ringwomb was the
      dominating reason for dystocia for m.d. (43.5%) as well as for c.s. (73.7%),
      followed by obstetrics due to fetal abnormal presentation and/or position or
      posture (25.2% m.d.; 1.1% c.s.), secondary oversized fetuses due to postmortal
      emphysema and edema (19.1% m.d.; 10.7% c.s.), followed by primary relative or
      absolute oversized fetuses (1.0% m.d.; 4.8% c.s.) and simultaneously presentation
      of multiple fetuses (4.2% m.d.). Other causes of dystocia remained scarce (i.e.
      uterine torsion, hydrallantois, abdominal or perineal hernia). There rested an
      amount of sheep (7.1%) with preterm s.c. because of continuous pressure and pain
      symptoms followed by infections or injuries of the prolapsed vagina and/or
      rectum, pregnancy toxemia and other reasons. The main indication for fetotomy in
      sheep were fetuses with postmortal edema and emphysema (80.0%), deformity of the
      kids (20.0%) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720548
TI  - [Serodiagnosis of Lyme borreliosis: development and evaluation of a test system
      for epidemiological studies in the dog].
AB  - The aim of the study was to develop and validate a serological test system for
      extended epidemiological investigations to which extend dogs were exposed to
      Borrelia burgdorferi. For this purpose, 121 samples of dogs which were suspect of
      an infection and submitted to the laboratory for serological testing, were
      investigated in an immunofluorescence test (IFT) and to different enzyme-linked
      immunosorbent assays (ELISA). Valuation of the ELISA systems was assessed in
      relation to the IFT. Sensitivity, specificity and predictive values were
      calculated for negative, positive and also borderline values. In the screening
      test all samples with a positive titre in IFT were judged positive. Samples
      negative in IFT showed negative results in the screening in only 86%. All samples
      positive in screening or of borderline value in IFT were again tested using a
      confirmatory ELISA. By this procedure a specificity of 100% and a sensitivity of
      85% was calculated for samples with positive or negative IFT titres,
      respectively. Samples with IFT borderline titres (1:64 or 1:128) were judged
      negative in this ELISA in 80% and borderline in 16%. Checking of selected samples
      in an immunodot test confirmed the ELISA results. Sera being negative in ELISA
      showed also no specific reaction in this test. When considering the possibility
      of false positive reactions in IFT, rather high percentages of sensitivity and
      specificity could be found. Because all real positive samples could be detected
      using the confirmatory ELISA as a single test, there is no further need in
      epidemiological investigations to use the screening test. For specific problems
      the Western blot can be used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720549
TI  - [Typing of 17 porcine enterovirus isolates from polio encephalomyelitis cases
      during the years 1983-1991].
AB  - Seventeen strains of porcine enteroviruses (PEV) were isolated from organs of 119
      pigs with symptoms of polioencephalomyelitis submitted to the State Veterinary
      Institute Arnsberg/Westphalia between 1983 and 1991. 15 isolates originated from
      the central nervous system and 2 from organ suspensions made up of a brain-spleen
      pool and a lung-spleen-lymph node-pool, respectively. Isolates were assigned to 7
      PEV types which were present at the following frequencies: PEV1: 2x; PEV2: 6x;
      PEV4: 3x; PEV5: 1x; PEV6: 2x; PEV 12: 1x; PEV 13: 2x. Mortality rates of affected
      groups exhibited an age-dependent curvilinear relationship suggesting that the
      PEV involved possessed a rather similar low to medium grade neurovirulence,
      irrespective of type. Exceptions were 1 herd with 100% mortality at the age of 10
      18 weeks from which PEV2 strain 6793/83 was isolated (described earlier) and a
      second herd with 18% mortality at the age of 14-18 weeks from which PEV types 1,
      2 and 4 were recovered. Sensitivity of 5 cell lines for the isolation of PEV was
      compared. Rates of isolation from organ suspensions which had proved positive in
      any of the cell lines tested were as follows: PS-EK: 77%; IB-RS-2: 63%; ST: 56%;
      PK-15: 47%; BHK21 (CT): 10%.

PMID- 7720550
TI  - [Follow-up studies of the detection of IgG1 antibodies to Coxiella burnetii in
      blood and milk from cattle in relation to the reproductive cycle and milk
      production].
AB  - During a 14 month period, 36 dairy cattle were selected from a herd (n = 103),
      after IgG1 antibodies to Coxiella burnetii had repeatedly been detected in blood
      and milk, as measured by ELISA. ELISA results were analyzed with reference to
      reproductive cycle, daily milk yield, as well as daily concentration, and output
      of milk protein. The rate of positive blood samples slightly grew from 47.6% in
      the non-pregnant period, and 46.8% in the first half of pregnancy to 52.0% in the
      second half of pregnancy. In contrast, results of milk ELISA changed
      significantly from non-pregnant period to first, and second half of pregnancy,
      with increases from 23.8 to 38.5, and 64.6% of positive milk samples. Moreover,
      milk samples showed negative correlations between ELISA OD405 values and daily
      milk yield, as well as daily output of milk protein.

PMID- 7720551
TI  - Caudalization by the amphibian organizer: brachyury, convergent extension and
      retinoic acid.
AB  - Caudalization, which is proposed to be one of two functions of the amphibian
      organizer, initiates posterior pathways of neural development in the dorsalized
      ectoderm. In the absence of caudalization, dorsalized ectoderm only expresses the
      most anterior (archencephalic) differentiation. In the presence of caudalization,
      dorsalized ectorderm develops various levels of posterior neural tissues,
      depending on the extent of caudalization. A series of induction experiments have
      shown that caudalization is mediated by convergent extension: cell motility that
      is based on directed cell intercalation, and is essential for the morphogenesis
      of posterior axial tissues. During amphibian development, convergent extension is
      first expressed all-over the mesoderm and, after mesoderm involution, it becomes
      localized to the posterior mid-dorsal mesoderm, which produces notochord. This
      expression pattern of specific down regulation of convergent extension is also
      followed by the expression of the brachyury homolog. Furthermore, mouse brachyury
      has been implicated in the regulation of tissue elongation on the one hand, and
      in the control of posterior differentiation on the other. These observations
      suggest that protein encoded by the brachyury homolog controls the expression of
      convergent extension in the mesoderm. The idea is fully corroborated by a genetic
      study of mouse brachyury, which demonstrates that the gene product produces
      elongation of the posterior embryonic axis. However, there exists evidence for
      the induction of posterior dorsal mesodermal tissues, if brachyury homolog
      protein is expressed in the ectoderm. In both cases the brachyury homolog
      contributes to caudalization. A number of other genes appear to be involved in
      caudalization. The most important of these is pintavallis, which contains a fork
      head DNA binding domain. It is first expressed in the marginal zone. After
      mesoderm involution, it is present not only in the presumptive notochord, but
      also in the floor plate. This is in contrast to the brachyury homolog, whose
      expression is restricted to mesoderm. The morphogenetic effects of exogenous RA
      on anteroposterior specification during amphibian embryogenesis are reviewed. The
      agent inhibits archencephalic differentiation and enhances differentiation of
      deuterencephalic and trunk levels. Thus the effect of exogenous RA on
      morphogenesis of CNS is very similar to that of caudalization, which is proposed
      to occur through the normal action of the organizer. According to a detailed
      analysis of the effect of lithium on morphogenesis induced by the Cynops
      organizer, lithium has a caudalizing effect closely comparable with that of RA.
      Furthermore, lithium induces convergent extension in the prechordal plate, which
      normally does not show cell motility.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7720552
TI  - Regulation of motor neuron dendrite growth by NMDA receptor activation.
AB  - Spinal motor neurons undergo great changes in morphology, electrophysiology and
      molecular composition during development. Some of this maturation occurs
      postnatally when limbs are employed for locomotion, suggesting that neuronal
      activity may influence motor neuron development. To identify features of motor
      neurons that might be regulated by activity we first examined the structural
      development of the rat motor neuron cell body and dendritic tree labeled with
      cholera toxin-conjugated horseradish peroxidase. The motor neuron cell body and
      dendrites in the radial and rostrocaudal axes grew progressively over the first
      month of life. In contrast, the growth of the dendritic arbor/cell and number of
      dendritic branches was biphasic with overabundant growth followed by regression
      until the adult pattern was achieved. We next examined the influence of
      neurotransmission on the development of these motor neuron features. We found
      that antagonism of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor
      inhibited cell body growth and dendritic branching in early postnatal life but
      had no effect on the maximal extent of dendrite growth in the radial and
      rostrocaudal axes. The effects of NMDA receptor antagonism on motor neurons and
      their dendrites was temporally restricted; all of our anatomic measures of
      dendrite structure were resistant to NMDA receptor antagonism in adults. These
      results suggest that the establishment of mature motor neuron dendritic
      architecture results in part from dendrite growth in response to afferent input
      during a sensitive period in early postnatal life.

PMID- 7720553
TI  - Initial steps of myogenesis in somites are independent of influence from axial
      structures.
AB  - Formation of paraxial muscles in vertebrate embryos depends upon interactions
      between early somites and the neural tube and notochord. Removal of both axial
      structures results in a complete loss of epaxial myotomal muscle, whereas
      hypaxial and limb muscles develop normally. We report that chicken embryos, after
      surgical removal of the neural tube at the level of the unsegmented paraxial
      mesoderm, start to develop myotomal cells that express transcripts for the muscle
      specific regulators MyoD and myogenin. These cells also make desmin, indicating
      that the initial steps of axial skeletal muscle formation can occur in the
      absence of the neural tube. However, a few days following the extirpation, the
      expression of MyoD and myogenin transcripts gradually disappears, and becomes
      almost undetectable after 4 days. From these observations we conclude that the
      neural tube is not required for the generation of the skeletal muscle cell
      lineage, but may support the survival or maitenance of further differentiation of
      the myotomal cell compartment. Notochord transplanted medially or laterally to
      the unsegmented paraxial mesoderm leads to a ventralization of axial structures
      but does not entirely prevent the early appearance of myoblasts expressing MyoD
      transcripts. However, the additional notochord inhibits subsequent development
      and maturation of myotomes. Taken together, our data suggest that neural tube
      promotes, and notochord inhibits, the process of myogenesis in axial muscles at a
      developmental step following the initial expression of myogenic bHLH regulators.

PMID- 7720554
TI  - MyoD expression marks the onset of skeletal myogenesis in Myf-5 mutant mice.
AB  - The expression pattern of myogenic regulatory factors and myotome-specific
      contractile proteins was studied during embryonic development of Myf-5 mutant
      mice by in situ hybridization and immunohistochemistry. In contrast to somites in
      wild-type embryos, no expression of myogenin and Myf-6 (MRF4), or any other
      myotomal markers was detected in mutant animals at E9.0 and E10.0 indicating that
      Myf-5 plays a crucial role during this developmental period. Significantly, the
      onset of MyoD expression in rostral somites of E10.5 embryos was unaffected by
      the Myf-5 mutation suggesting that the activation of the MyoD gene occurs
      independently of Myf-5 at the correct developmental time. Immediately after the
      activation of MyoD myogenin transcripts and protein accumulated within the
      myotome. The first contractile proteins of the sarcomeric apparatus appeared
      slightly later. By E11.5 the expression of muscle markers were indistinguishable
      between wild-type and Myf-5 mutant mice. The migration of muscle precursor cells
      that leave the somites to form limb musculature was monitored in Myf-5-mutant
      mice by Pax-3 expression. Pax-3-positive cells were equally found in somites and
      limbs of E10.0 wild-type and mutant mice indicating that myogenic factor
      expression at the level of somites is not a prerequisite for determination and
      subsequent migration of limb precursor cells.

PMID- 7720555
TI  - Multiple requirements for the receptor serine/threonine kinase thick veins reveal
      novel functions of TGF beta homologs during Drosophila embryogenesis.
AB  - Differentiation of distinct cell types at specific locations within a developing
      organism depends largely on the ability of cells to communicate. A major class of
      signalling proteins implicated in cell to cell communication is represented by
      members of the TGF beta superfamily. A corresponding class of transmembrane
      serine/threonine kinases has recently been discovered that act as cell surface
      receptors for ligands of the TGF beta superfamily. The product of the Drosophila
      gene decapentaplegic (dpp) encodes a TGF beta homolog that plays multiple roles
      during embryogenesis and the development of imaginal discs. Here we describe the
      complex expression pattern of thick veins (tkv), which encodes a receptor for
      dpp. We make use of tkv loss-of-function mutations to examine the consequences of
      the failure of embryonic cells to respond to dpp and/or other TGF beta homologs.
      We find that while maternal tkv product allows largely normal dorsoventral
      pattering of the embryo, zygotic tkv activity is indispensable for dorsal closure
      of the embryo after germ band retraction. Furthermore, tkv activity is crucial
      for patterning the visceral mesoderm; in the absence of functional tkv gene
      product, visceral mesoderm parasegment 7 cells fail to express Ultrabithorax, but
      instead accumulate Antennapedia protein. The tkv receptor is therefore involved
      in delimiting the expression domains of homeotic genes in the visceral mesoderm.
      Interestingly, tkv mutants fail to establish a proper tracheal network. Tracheal
      braches formed by cells migrating in dorsal or ventral directions are absent in
      tkv mutants. The requirements for tkv in dorsal closure, visceral mesoderm and
      trachea development assign novel functions to dpp or a closely related member of
      the TGF beta superfamily.

PMID- 7720556
TI  - Open brain, a new mouse mutant with severe neural tube defects, shows altered
      gene expression patterns in the developing spinal cord.
AB  - We describe a new mouse mutation, designated open brain (opb), which results in
      severe defects in the developing neural tube. Homozygous opb embryos exhibited an
      exencephalic malformation involving the forebrain, midbrain and hindbrain
      regions. The primary defect of the exencephaly could be traced back to a failure
      to initiate neural tube closure at the midbrain-forebrain boundary. Severe
      malformations in the spinal cord and dorsal root ganglia were observed in the
      thoracic region. The spinal cord of opb mutant embryos exhibited an abnormal
      circular to oval shape and showed defects in both ventral and dorsal regions. In
      severely affected spinal cord regions, a dorsalmost region of cells negative for
      Wnt-3a, Msx-2, Pax-3 and Pax-6 gene expression was detected and dorsal expression
      of Pax-6 was increased. In ventral regions, the area of Shh and HNF-3 beta
      expression was enlarged and the future motor neuron horns appeared to be reduced
      in size. These observations indicate that opb embryos exhibit defects in the
      specification of cells along the dorsoventral axis of the developing spinal cord.
      Although small dorsal root ganglia were formed in opb mutants, their metameric
      organization was lost. In addition, defects in eye development and malformations
      in the axial skeleton and developing limbs were observed. The implications of
      these findings are discussed in the context of dorsoventral patterning of the
      developing neural tube and compared with known mouse mutants exhibiting similar
      defects.

PMID- 7720557
TI  - Transcriptional regulation of string (cdc25): a link between developmental
      programming and the cell cycle.
AB  - During postblastoderm embryogenesis in Drosophila, cell cycles progress in an
      invariant spatiotemporal pattern. Most of these cycles are differentially timed
      by bursts of transcription of string (cdc25), a gene encoding a phosphatase that
      triggers mitosis by activating the Cdc2 kinase. An analysis of string expression
      in 36 pattern-formation mutants shows that known patterning genes act locally to
      influence string transcription. Embryonic expression of string gene fragments
      shows that the complete pattern of string transcription requires extensive cis
      acting regulatory sequences (> 15.3 kb), but that smaller segments of this
      regulatory region can drive proper temporal expression in defined spatial
      domains. We infer that string upstream sequences integrate many local signals to
      direct string's transcriptional program. Finally, we show that the spatiotemporal
      progression of string transcription is largely unaffected in mutant embryos
      specifically arrested in G2 of cycles 14, 15, or 16, or G1 of cycle 17. Thus,
      there is a regulatory hierarchy in which developmental inputs, not cell cycle
      inputs, control the timing of string transcription and hence cell cycle
      progression.

PMID- 7720558
TI  - Role of leukemia inhibitory factor and its receptor in mouse primordial germ cell
      growth.
AB  - The pleiotropic cytokine leukemia inhibitory factor (LIF) is able to promote the
      growth of mouse primordial germ cells (PGCs) in culture. It is unclear whether
      LIF acts directly on PGCs or indirectly via feeder cells or embryonic somatic
      cells. To understand the role of LIF in PGC growth, we have carried out molecular
      and cell culture analyses to investigate the role of both the LIF ligand and its
      receptor in PGC development. LIF is able to stimulate PGC growth independently of
      the presence of feeder cells supporting the hypothesis that LIF acts directly on
      PGCs to promote their growth. We show here that transcripts for the low-affinity
      LIF receptor (LIFR), an integral component of the functional LIF receptor
      complex, are expressed in the developing gonad. Fluorescence-activated cell
      sorter (FACS) analysis, using an anti-LIFR antiserum, demonstrates that LIFR is
      present on the surface of PGCs, suggesting that PGCs are likely to be a direct
      target of LIF action in culture. Signalling via LIFR is essential for PGC growth
      in culture since the anti-LIFR antiserum, which blocks LIF binding to its
      receptor, abolishes PGC survival in culture. Two LIF-related cytokines, namely
      oncostatin M and ciliary neurotrophic factor, can also promote PGC growth in
      culture in addition to LIF. Thus one or more of these LIFR-dependent cytokines
      may play an important role in PGC development in mice.

PMID- 7720559
TI  - Three maternal coordinate systems cooperate in the patterning of the Drosophila
      head.
AB  - In contrast to the segmentation of the embryonic trunk region which has been
      extensively studied, relatively little is known about the development and
      segmentation of the Drosophila head. Proper development of the cephalic region
      requires the informational input of three of the four maternal coordinate
      systems. Head-specific gene expression is set up in response to a complex
      interaction between the maternally provided gene products and zygotically
      expressed genes. Several zygotic genes involved in head development have recently
      been characterized. A genetic analysis suggests that the segmentation of the head
      may use a mechanism different from the one acting in the trunk. The two genes of
      the sloppy paired locus (slp1 and slp2) are also expressed in the embryonic head.
      slp1 plays a predominant role in head formation while slp2 is largely
      dispensible. A detailed analysis of the slp head phenotype suggests that slp is
      important for the development of the mandibular segment as well as two adjacent
      pregnathal segments (antennal and ocular). Our analysis of regulatory
      interactions of slp with maternal and zygotic genes suggests that it behaves like
      a gap gene. Thus, phenotype and regulation of slp support the view that slp acts
      as a head-specific gap gene in addition to its function as a pair-rule and
      segment polarity gene in the trunk. We show that all three maternal systems
      active in the cephalic region are required for proper slp expression and that the
      different systems cooperate in the patterning of the head. The terminal and
      anterior patterning system appear to be closely linked. This cooperation is
      likely to involve a direct interaction between the bcd morphogen and the terminal
      system. Low levels of terminal system activity seem to potentiate bcd as an
      activator of slp, whereas high levels down-regulate bcd rendering it inactive.
      Our analysis suggests that dorsal, the morphogen of the dorsoventral system, and
      the head-specific gap gene empty spiracles act as repressor and corepressor in
      the regulation of slp. We discuss how positional information established
      independently along two axes can act in concert to control gene regulation in two
      dimensions.

PMID- 7720560
TI  - The mouse tissue plasminogen activator gene 5' flanking region directs
      appropriate expression in development and a seizure-enhanced response in the CNS.
AB  - Tissue plasminogen activator (t-PA) is a secreted serine protease implicated in
      multiple aspects of development. In the adult rat brain, transcription of t-PA is
      an immediate-early response in the hippocampus following treatments that induce
      neuronal plasticity. To study the sequence elements that govern transcription of
      this gene, in situ analysis was used to define t-PA's temporal and spatial
      expression pattern in midgestation embryos. Transgenic mice were then generated
      carrying t-PA 5' flanking sequences linked to the E. coli lacZ gene. Constructs
      containing 4 kb of the flanking sequences (4.0TAMGAL) confer beta-galactosidase
      activity mostly to the same tissues that exhibit high levels of t-PA mRNA by in
      situ analysis. In 4.0TAMGAL embryos from embryonic day 8.5 (E8.5) to 13.5
      (E13.5), the majority of expression observed is localized to neural ectoderm
      derived tissues. beta-galactosidase activity is first detected in restricted
      neuromeres in the midbrain and diencephalon, at E8.5 and E9.5 respectively. At
      E10.5, transgene expression is observed in neural crest-derived cranial nerves
      and dorsal root ganglia, but not placode-derived cranial nerves. From E10.5 to
      E13.5, beta-galactosidase activity is observed in postmitotic neurons of the
      midbrain, spinal cord, neural retina and the developing olfactory system. beta
      galactosidase activity is also detected in areas undergoing tissue remodeling
      such as the pinna of the ear, whisker follicles and the limbs. In adult mice,
      lacZ is expressed in the hippocampus and this expression was found to be enhanced
      upon seizure in the giant pyramidal neurons of CA3. These results reinforce the
      concept that t-PA plays a role in neurogenesis and morphogenesis, and identifies
      the promoter region that directs its transcriptional regulation both in
      development and in the CNS.

PMID- 7720561
TI  - Function of Drosophila ovo+ in germ-line sex determination depends on X
      chromosome number.
AB  - Germ-line sex determination in Drosophila melanogaster requires an assessment of
      the number of X chromosomes as measured against autosomal standards (XX = female,
      X = male) and signaling from the soma. Both of these sex determination cues are
      required for female-specific Sex-lethal+ function in germ cells. The ovo+ locus
      encodes zinc finger protein(s) required for female-specific splicing of Sex
      lethal+ pre-mRNA, making ovo+ a candidate function acting between the two
      principal cues and Sex-lethal+. We have made ovo reporter genes and find that
      they show high activity in the germ line of females and low activity in the germ
      line of males. XY flies transformed into somatic females do not show high levels
      of reporter activity, while XX flies transformed into somatic males do. This
      shows that high level ovo+ expression depends on the number of X chromosomes, not
      the somatic sexual signals. The requirement for ovo+ function is restricted to XX
      flies. Mutations in ovo have no effect on XY males, X0 males or XY females, but
      have pronounced effects on germ cell viability in XX females, XX females with sex
      transformed germ lines, and XX males indicating that ovo+ gene products are
      required for events occurring only in flies with two X chromosomes.

PMID- 7720562
TI  - Mouse embryonic germ (EG) cell lines: transmission through the germline and
      differences in the methylation imprint of insulin-like growth factor 2 receptor
      (Igf2r) gene compared with embryonic stem (ES) cell lines.
AB  - Primordial germ cells of the mouse cultured on feeder layers with leukemia
      inhibitory factor, Steel factor and basic fibroblast growth factor give rise to
      cells that resemble undifferentiated blastocyst-derived embryonic stem cells.
      These primordial germ cell-derived embryonic germ cells can be induced to
      differentiate extensively in culture, form teratocarcinomas when injected into
      nude mice and contribute to chimeras when injected into host blastocysts. Here,
      we report the derivation of multiple embryonic germ cell lines from 8.5 days post
      coitum embryos of C57BL/6 inbred mice. Four independent embryonic germ cell lines
      with normal male karyotypes have formed chimeras when injected into BALB/c host
      blastocysts and two of these lines have transmitted coat color markers through
      the germline. We also show that pluripotent cell lines capable of forming
      teratocarcinomas and coat color chimeras can be established from primordial germ
      cells of 8.0 days p.c. embryos and 12.5 days p.c. genital ridges. We have
      examined the methylation status of the putative imprinting box of the insulin
      like growth factor type 2 receptor gene (Igf2r) in these embryonic germ cell
      lines. No correlation was found between methylation pattern and germline
      competence. A significant difference was observed between embryonic stem cell and
      embryonic germ cell lines in their ability to maintain the methylation imprint of
      the Igf2r gene in culture. This may illustrate a fundamental difference between
      these two cell types.

PMID- 7720563
TI  - Engrailed-mediated repression of Ultrabithorax is necessary for the parasegment 6
      identity in Drosophila.
AB  - The homeotic genes of Drosophila are expressed in overlapping domains along the
      anterior-to-posterior axis and specify the distinct morphological patterns of
      each parasegment. Within single parasegments, the levels of homeotic gene
      expression are often modulated, in part because of cross-regulation by other
      homeotic gene products. However, the functional significance of different levels
      of homeotic gene expression is unclear. Here modulations in Ultrabithorax (Ubx)
      expression within parasegment 6 are examined. Specifically, Ubx is shown to be
      down-regulated in the posterior compartment of this parasegment by engrailed
      (en). The significance of Ubx repression by en was demonstrated by characterizing
      the expression of the Ubx target gene, Distal-less (Dll). In the posterior
      compartment of parasegment 6, Dll is normally expressed in a small cluster of
      cells. If Ubx is expressed uniformly via a heat-shock promoter, Dll is
      inappropriately repressed in these posterior compartment cells. In the anterior
      compartment of parasegment 6, Dll is normally repressed by high levels of Ubx.
      However, if en is expressed uniformly via a heat-shock promoter, Ubx is repressed
      and Dll is derepressed. Because Dll is required for the development of larval
      sensory structures, these results demonstrate that en-mediated repression of Ubx
      in the posterior compartment is necessary for the morphology of parasegment 6.
      Thus, different levels of homeotic gene expression can be important for their
      segmental patterning functions.

PMID- 7720564
TI  - Distribution of, and a putative role for, the cell-surface neutral metallo
      endopeptidases during mammalian craniofacial development.
AB  - Endopeptidase-24.11 (neutral endopeptidase, neprilysin, 'enkephalinase', EC
      3.4.24.11) and endopeptidase-24.18 (endopeptidase-2, meprin, EC 3.4.24.18) are
      cell-surface zinc-dependent metallo-endopeptidases able to cleave a variety of
      bioactive peptides including growth factors. We report the first study of the
      cellular and tissue distribution of both enzymes and of the mRNA for NEP during
      embryonic development in the rat. Endopeptidase-24.11 protein was first detected
      at E10 in the lining of the gut and, at E12, the enzyme was present on the
      notochord, medial and lateral nasal processes, otocyst, mesonephros, heart and
      neuroepithelium. In contrast, at this time endopeptidase-24.18 was present only
      on the apical surface of the neuroepithelial cells. By E14 and E16, NEP was also
      detected in a wide range of craniofacial structures, notably the palatal
      mesenchyme, the choroid plexus, tongue and perichondrium. The distribution of
      endopeptidase-24.18 at these stages was restricted to the inner ear, the nasal
      conchae, and ependymal layer of the brain ventricles and the choroid plexus.
      Although endopeptidase-24.11 had been detectable in the craniofacial vasculature
      at E12 and E14, this was no longer apparent at E16. Significantly, the
      distribution of endopeptidase-24.11 mRNA closely matched the immunolocalization
      of the protein at all stages investigated. In order to explore the functional
      role of these enzymes, inhibition studies were carried out using two selective
      inhibitors of endopeptidase-24.11, phosphoramidon and thiorphan. E9.5 and E10.5
      embryos exposed to either inhibitor displayed a characteristic, asymmetric
      abnormality consisting of a spherical swelling, possibly associated with a
      haematoma, predominantly on the left side of the prosencephalon, and the severity
      of this defect appeared to be a dose-dependent phenomenon. This study suggests
      that these enzymes play previously unrecognized roles during mammalian embryonic
      development.

PMID- 7720565
TI  - GATA factor activity is required for the trophoblast-specific transcriptional
      regulation of the mouse placental lactogen I gene.
AB  - The molecular determinants governing tissue-specific gene expression in the
      placenta are at present only poorly defined, particularly with respect to the
      regulation of specific hormone genes whose products are vital to embryonic
      development and the maintenance of a nurturing maternal environment. In
      continuing our analysis of the trophoblast-specific expression of the mouse
      placental lactogen I gene, we now demonstrate that the transcription factors GATA
      2 and GATA-3 regulate the activity of this gene promoter. These factors are
      expressed in placental trophoblast cells, with peak levels of the GATA-2, GATA-3
      and placental lactogen I mRNAs each accumulating at midgestation. Analysis of a
      region of the placental lactogen I gene promoter, previously shown to be
      sufficient for directing trophoblast-specific transcription, revealed the
      presence of three consensus binding sites for GATA-2 or GATA-3. Both GATA-2 and
      GATA-3 bind to these sites in vitro and mutation of these sites results in a
      significant decrease in promoter activity as assayed by transient transfection
      into the choriocarcinoma-derived cell line Rcho-1, which expresses endogenous
      GATA-2 and GATA-3. Furthermore, overexpression of GATA factors in Rcho-1 cells
      stimulates transcription from a co-transfected placental lactogen I gene
      promoter. Most significantly, expression of GATA-2 or GATA-3 was found to induce
      transcription from this promoter in transfected non-trophoblast (fibroblast)
      cells. These data indicate that GATA factors are both limiting and required
      transcriptional regulatory molecules in placental trophoblasts, and that the
      tissue specificity of the placental lactogen I gene is determined, at least in
      part, by GATA-2 and/or GATA-3.

PMID- 7720566
TI  - Relationship between retinoic acid and sonic hedgehog, two polarizing signals in
      the chick wing bud.
AB  - Local application of all-trans-retinoic acid (RA) to the anterior margin of chick
      limb buds results in pattern duplications reminescent of those that develop after
      grafting cells from the zone of polarizing activity (ZPA). RA may act directly by
      conferring positional information to limb bud cells, or it may act indirectly by
      creating a polarizing region in the tissue distal to the RA source. Here we
      demonstrate that tissue distal to an RA-releasing bead acquires polarizing
      activity in a dose-dependent manner. Treatments with pharmacological (beads
      soaked in 330 micrograms/ml) and physiological (beads soaked in 10 micrograms/ml)
      doses of RA are equally capable of inducing digit pattern duplication.
      Additionally, both treatments induce sonic hedgehog (shh; also known as
      vertebrate hedgehog-1, vhh-1), a putative ZPA morphogen and Hoxd-11, a gene
      induced by the polarizing signal. However, tissue transplantation assays reveal
      that pharmacological, but not physiological, doses create a polarizing region.
      This differential response could be explained if physiological doses induced less
      shh than pharmacological doses. However, our in situ hybridization analyses
      demonstrate that both treatments result in similar amounts of mRNA encoding this
      candidate ZPA morphogen. We outline a model describing the apparently disparate
      effects of pharmacologic and physiological doses RA on limb bud tissue.

PMID- 7720567
TI  - Differential expression of Broad-Complex transcription factors may forecast
      tissue-specific developmental fates during Drosophila metamorphosis.
AB  - The steroid hormone ecdysone initiates metamorphosis in Drosophila melanogaster
      by activating a cascade of gene activity that includes primary response
      transcriptional regulators and secondary response structural genes. The Broad
      Complex (BR-C) primary response gene is composed of several distinct genetic
      functions and encodes a family of related transcription factor isoforms. Our
      objective was to determine whether BR-C isoforms were components of the primary
      ecdysone response in all tissues and whether tissue-specific isoform expression
      is associated with tissue-specific metamorphic outcomes. We used specific
      antibody reagents that recognize and distinguish among the Z1, Z2 and Z3 BR-C
      protein isoforms to study protein expression patterns during the initial stages
      of metamorphosis. Western blot analyses demonstrated that BR-C isoforms are
      induced at the onset of metamorphosis, each with unique kinetics of induction and
      repression. Whole-mount immunostaining showed that the BR-C proteins accumulate
      in the nuclei of all larval and imaginal tissues indicating that the BR-C is
      induced as a primary response in many tissues. Several tissues express different
      levels and combinations of the BR-C isoforms suggesting that the BR-C is
      important in determining the tissue-specific outcome of many parallel ecdysone
      response cascades. For example, prepupal salivary glands (destined for histolysis
      during metamorphosis) express Z1 isoforms while imaginal discs (destined for cell
      differentiation and morphogenesis) shift from the synthesis of Z2 isoforms to the
      synthesis of Z1 isoforms. The prepupal central nervous system (destined for
      tissue remodeling) expresses all isoforms, with Z3 predominating. Salivary gland
      chromosome immunostaining indicated that BR-C proteins interact directly with
      numerous loci in the polytene genome. Finally, western blot analyses showed that
      distinct BR-C genetic functions can be correlated with single and specific BR-C
      protein isoforms.

PMID- 7720568
TI  - Gp330 is specifically expressed in outer cells during epithelial differentiation
      in the preimplantation mouse embryo.
AB  - During preimplantation development of the mouse embryo, a layer of outer cells
      differentiates into a perfect epithelium, the trophectoderm. The divergence
      between the trophectoderm and the inner cell mass takes place from the 8-cell
      stage to the 64-cell stage and precedes their commitment at the blastocyst stage.
      In this work, we have investigated the expression of gp330, a 330 x 10(3) M(r)
      glycoprotein found in clathrin-coated areas of the plasma membrane of some
      epithelial cells characterized by a high level of endocytic activity. Our results
      show that gp330 is first synthesized in 16-cell stage embryos and that its
      appearance is restricted to outer cells until the blastocyst stage. Furthermore,
      its expression is repressed in inner cells at a post-transcriptional level,
      probably through the development of extensive cell-cell contacts.

PMID- 7720569
TI  - Roles of heterotrimeric and monomeric G proteins in sperm-induced activation of
      mouse eggs.
AB  - Results of several lines of experimentation suggest that sperm-induced egg
      activation has several features in common with G protein-coupled receptor signal
      transduction mechanisms. We report that microinjection of GDP beta S into
      metaphase II-arrested mouse eggs blocks sperm-induced egg activation. Since GDP
      beta S inactivates both heterotrimeric and monomeric classes of G proteins, the
      involvement of members of each of these families in sperm-induced egg activation
      was evaluated. Neither pertussis toxin treatment of eggs nor microinjection of
      eggs with inhibitory antibodies toward G alpha q blocked sperm-induced egg
      activation. Nevertheless, microinjection of phosducin, a protein that binds
      tightly to free G protein beta gamma subunits, specifically inhibited second
      polar body emission, the fertilization evoked decrease of H1 kinase activity and
      pronucleus formation. Microinjection of phosducin, however, did not inhibit the
      fertilization-induced modifications of the zona pellucida and microinjection of
      beta gamma t did not result in egg activation in the absence of sperm.
      Inactivation of the monomeric Rho family of G proteins with C3 transferase from
      Clostridium botulinum inhibited emission of the second polar body and cleavage to
      the 2-cell stage, but did not affect the modifications of the zona pellucida or
      pronucleus formation. Microinjection of Rasval12, which is a constitutively
      active form of Ras, did not result in egg activation in the absence of sperm.
      Moreover, microinjection of either an anti-Ras neutralizing antibody (Y13-259) or
      a dominant negative form of Ras (RasT) did not affect events of sperm-induced egg
      activation. In contrast, microinjection of RasT inhibited embryo cleavage to the
      2-cell stage. These results suggest that both heterotrimeric and monomeric G
      proteins are involved in various aspects of sperm-induced egg activation.

PMID- 7720570
TI  - Combinatorial specification of blastomere identity by glp-1-dependent cellular
      interactions in the nematode Caenorhabditis elegans.
AB  - Most somatic cells in the nematode Caenorhabditis elegans arise from AB, the
      anterior blastomere of the 2-cell embryo. While the daughters of AB, ABa and ABp,
      are equivalent in potential at birth, they adopt different fates as a result of
      their unique positions. One such difference is that the distribution of epidermal
      precursors arising from ABp is reversed along the anterior-posterior axis
      relative to those arising from ABa. We have found that a strong mutation in the
      glp-1 gene eliminates this ABa/ABp difference. Furthermore, extensive cell
      lineage analyses showed that ABp adopts an ABa-like fate in this mutant. This
      suggests that glp-1 acts in a cellular interaction that makes ABp distinct from
      ABa. One ABp-specific cell type was previously shown to be induced by an
      interaction with a neighboring cell, P2. By removing P2 from early embryos, we
      have found that the widespread differences between ABa and ABp arise from
      induction of the entire ABp fate by P2. Lineage analyses of genetically and
      physically manipulated embryos further suggest that the identifies of the AB
      great-granddaughters (AB8 cells) are controlled by three regulatory inputs that
      act in various combinations. These inputs are: (1) induction of the ABp-specific
      fate by P2, (2) a previously described induction of particular AB8 cells by a
      cell called MS, and (3) a process that controls whether an AB8 cell is an
      epidermal precursor in the absence of either induction. When an AB8 cell is
      caused to receive a new combination of these regulatory inputs, its lineage
      pattern is transformed to resemble the lineage of the wild-type AB8 cell normally
      receiving that combination of inputs. These lineage patterns are faithfully
      reproduced irrespective of position in the embryo, suggesting that each
      combination of regulatory inputs directs a unique lineage program that is
      intrinsic to each AB8 cell.

PMID- 7720571
TI  - Products, genetic linkage and limb patterning activity of a murine hedgehog gene.
AB  - The hedgehog (hh) segmentation gene of Drosophila melanogaster encodes a secreted
      signaling protein that functions in the patterning of larval and adult
      structures. Using low stringency hybridization and degenerate PCR primers, we
      have isolated complete or partial hh-like sequences from a range of invertebrate
      species including other insects, leech and sea urchin. We have also isolated
      three mouse and two human DNA fragments encoding distinct hh-like sequences. Our
      studies have focused upon Hhg-1, a mouse gene encoding a protein with 46% amino
      acid identity to hh. The Hhg-1 gene, which corresponds to the previously
      described vhh-1 or sonic class, is expressed in the notochord, ventral neural
      tube, lung bud, hindgut and posterior margin of the limb bud in developing mouse
      embryos. By segregation analysis the Hhg-1 gene has been localized to a region in
      proximal chromosome 5, where two mutations affecting mouse limb development
      previously have been mapped. In Drosophila embryos, ubiquitous expression of the
      Hhg-1 gene yields effects upon gene expression and cuticle pattern similar to
      those observed for the Drosophila hh gene. We also find that cultured quail cells
      transfected with a Hhg-1 expression construct can induce digit duplications when
      grafted to anterior or mid-distal but not posterior borders within the developing
      chick limb; more proximal limb element duplications are induced exclusively by
      mid-distal grafts. Both in transgenic Drosophila embryos and in transfected quail
      cells, the Hhg-1 protein product is cleaved to yield two stable fragments from a
      single larger precursor. The significance of Hhg-1 genetic linkage, patterning
      activity and proteolytic processing in Drosophila and chick embryos is discussed.

PMID- 7720572
TI  - Embryonic activation of the myoD gene is regulated by a highly conserved distal
      control element.
AB  - MyoD belongs to a small family of basic helix-loop-helix transcription factors
      implicated in skeletal muscle lineage determination and differentiation.
      Previously, we identified a transcriptional enhancer that regulates the embryonic
      expression of the human myoD gene. This enhancer had been localized to a 4 kb
      fragment located 18 to 22 kb upstream of the myoD transcriptional start site. We
      now present a molecular characterization of this enhancer. Transgenic and
      transfection analyses localize the myoD enhancer to a core sequence of 258 bp. In
      transgenic mice, this enhancer directs expression of a lacZ reporter gene to
      skeletal muscle compartments in a spatiotemporal pattern indistinguishable from
      the normal myoD expression domain, and distinct from expression patterns reported
      for the other myogenic factors. In contrast to the myoD promoter, the myoD
      enhancer shows striking conservation between humans and mice both in its sequence
      and its distal position. Furthermore, a myoD enhancer/heterologous promoter
      construct exhibits muscle-specific expression in transgenic mice, demonstrating
      that the myoD promoter is dispensable for myoD activation. With the exception of
      E-boxes, the myoD enhancer has no apparent sequence similarity with regulatory
      regions of other characterized muscle-specific structural or regulatory genes.
      Mutation of these E-boxes, however, does not affect the pattern of lacZ transgene
      expression, suggesting that myoD activation in the embryo is E-box-independent.
      DNase I protection assays reveal multiple nuclear protein binding sites in the
      core enhancer, although none are strictly muscle-specific. Interestingly,
      extracts from myoblasts and 10T1/2 fibroblasts yield identical protection
      profiles, indicating a similar complement of enhancer-binding factors in muscle
      and this non-muscle cell type. However, a clear difference exists between
      myoblasts and 10T1/2 cells (and other non-muscle cell types) in the chromatin
      structure of the chromosomal myoD core enhancer, suggesting that the myoD
      enhancer is repressed by epigenetic mechanisms in 10T1/2 cells. These data
      indicate that myoD activation is regulated at multiple levels by mechanisms that
      are distinct from those controlling other characterized muscle-specific genes.

PMID- 7720573
TI  - Combinatorial signals from the neural tube, floor plate and notochord induce
      myogenic bHLH gene expression in the somite.
AB  - The neural tube, floor plate and notochord are axial tissues in the vertebrate
      embryo which have been demonstrated to play a role in somite morphogenesis. Using
      in vitro coculture of tissue explants, we have monitored inductive interactions
      of these axial tissues with the adjacent somitic mesoderm in chick embryos. We
      have found that signals from the neural tube and floor plate/notochord are
      necessary for expression of the myogenic bHLH regulators MyoD, Myf5 and myogenin
      in the somite. Eventually somitic expression of the myogenic bHLH genes is
      maintained in the absence of the axial tissues. In organ culture, at early
      developmental stages (HH 11-), induction of myogenesis in the three most recently
      formed somites can be mediated by the neural tube together with the floor
      plate/notochord, while in more rostral somites (stages IV-IX) the neural tube
      without the floor plate/notochord is sufficient. By recombining somites and
      neural tubes from different axial levels of the embryo, we have found that a
      second signal is necessary to promote competence of the somite to respond to
      inducing signals from the neural tube. Thus, we propose that at least two signals
      from axial tissues work in combination to induce myogenic bHLH gene expression;
      one signal derives from the floor plate/notochord and the other signal derives
      from regions of the neural tube other than the floor plate.

PMID- 7720574
TI  - Myogenic cell migration from somites is induced by tissue contact with medial
      region of the presumptive limb mesoderm in chick embryos.
AB  - It is known that myogenic cells in limb buds are derived from somites. In order
      to examine the potential of the limb primordium (presumptive limb somatopleure)
      to induce myogenic cell migration, we transplanted chick presumptive limb
      somatopleure to the flank region of an embryo, a region that does not normally
      contribute myogenic cells to the limb. Somitic cell migration was examined using
      a vital labeling technique. When the presumptive limb somatopleure was
      transplanted and was in contact with the host flank somite, somitic-cell
      migration toward the graft was observed. The labeled somitic cells within the
      graft were identified as myogenic cells in two ways: first, we found that N
      cadherin-expressing cells appeared in the graft. Second, after 3 further days of
      incubation, the somitic cells formed dorsal and ventral masses and expressed
      sarcomeric myosin heavy chain within the graft. Cell migration occurred only when
      the somite was in contact with the medial region of the presumptive limb
      somatopleure. When the somite was not in contact with the limb somatopleure, or
      when the somite was in contact with the lateral region of the limb somatopleure,
      migration did not occur. These observations indicate that the potential to induce
      myogenic cell migration is restricted to the medial region of the presumptive
      limb somatopleure and that tissue contact is required.

PMID- 7720575
TI  - Postaxial polydactyly in forelimbs of CRABP-II mutant mice.
AB  - The cytoplasmic retinoic acid (RA)-binding protein CRABP-II is expressed widely
      throughout early morphogenesis in mouse embryo, but its expression becomes more
      restricted as organogenesis progresses. CRABP-II expression remains strong in the
      developing limb bud suggesting a role for this protein in limb patterning. Here,
      we show that the CRABP-II promoter can direct expression of a lacZ transgene in a
      specific posterior domain during limb bud development. In order to investigate in
      more detail the role played by CRABP-II in RA signal transduction, we have also
      generated mice homozygous for a null mutation of this gene. CRABPII-/- mice are
      viable and fertile but show a developmental defect of the forelimb, specifically
      an additional, postaxial digit. This digit is generally, but not exclusively,
      limited to a single forepaw of an individual animal. The penetrance of the
      phenotype varies according to the genetic background, occurring most frequently
      on the inbred 129Sv background (50%), less frequently on the C57Bl/6 background
      (30%) and rarely on the outbred CD1 background (10%). This developmental
      abnormality implies a role for CRABP-II in normal patterning of the limb.

PMID- 7720576
TI  - Genesis and prevention of spinal neural tube defects in the curly tail mutant
      mouse: involvement of retinoic acid and its nuclear receptors RAR-beta and RAR
      gamma.
AB  - A role for all-trans-retinoic acid in spinal neurulation is suggested by: (1) the
      reciprocal domains of expression of the retinoic acid receptors RAR-beta and RAR
      gamma in the region of the closed neural tube and open posterior neuropore,
      respectively, and (2) the preventive effect of maternally administered retinoic
      acid (5 mg/kg) on spinal neural tube defects in curly tail (ct/ct) mice. Using in
      situ hybridisation and computerised image analysis we show here that in ct/ct
      embryos, RAR-beta transcripts are deficient in the hindgut endoderm, a tissue
      whose proliferation rate is abnormal in the ct mutant, and RAR-gamma transcripts
      are deficient in the tail bud and posterior neuropore region. The degree of
      deficiency of RAR-gamma transcripts is correlated with the severity of delay of
      posterior neuropore closure. As early as 2 hours following RA treatment at 10
      days 8 hours post coitum, i.e. well before any morphogenetic effects are
      detectable, RAR-beta expression is specifically upregulated in the hindgut
      endoderm, and the abnormal expression pattern of RAR-gamma is also altered. These
      results suggest that the spinal neural tube defects which characterise the curly
      tail phenotype may be due to interaction between the ct gene product and one or
      more aspects of the retinoic acid signalling pathway.

PMID- 7720577
TI  - Homeobox genes and connective tissue patterning.
AB  - In vertebrates, limb tendons are derived from cells that migrate from the lateral
      plate mesoderm during early development. While some of the developmental steps
      leading to the formation of these tissues are known, little is known about the
      molecular mechanisms controlling them. We have identified two murine homeobox
      containing genes, Six 1 and Six 2, which are expressed in a complementary fashion
      during the development of limb tendons. Transcripts for both genes are found in
      different sets of phalangeal tendons. Six 1 and Six 2 also are expressed in
      skeletal and smooth muscle, respectively. These genes may participate in the
      patterning of the distal tendons of the limb phalanges by setting positional
      values along the limb axes.

PMID- 7720578
TI  - The Xenopus homologue of Otx2 is a maternal homeobox gene that demarcates and
      specifies anterior body regions.
AB  - In this paper we study Xotx2, a Xenopus homeobox gene related to orthodenticle, a
      gene expressed in the developing head of Drosophila. The murine cognate, Otx2, is
      first expressed in the entire epiblast of prestreak embryos and later in very
      anterior regions of late-gastrulae, including the neuroectoderm of presumptive
      fore- and mid-brain. In Xenopus, RNase protection experiments reveal that Xotx2
      is expressed at low levels throughout early development from unfertilized egg to
      late blastula, when its expression level significantly increases. Whole-mount in
      situ hybridization shows a localized expression in the dorsal region of the
      marginal zone at stage 9.5. At stage 10.25 Xotx2 is expressed in dorsal bottle
      cells and in cells of the dorsal deep zone fated to give rise to prechordal
      mesendoderm, suggesting a role in the specification of very anterior structures.
      In stage 10.5 gastrulae, Xotx2 transcripts start to be detectable also in
      presumptive anterior neuroectoderm, where they persist in subsequent stages.
      Various treatments of early embryos cause a general reorganization of Xotx2
      expression. In particular, retinoic acid treatment essentially abolishes Xotx2
      expression in neuroectoderm. Microinjection of Xotx2 mRNA in 1-, 2- and 4-cell
      stage embryos causes the appearance of secondary cement glands and partial
      secondary axes in embryos with reduced trunk and tail structures. The presence of
      the Xotx2 homeodomain is required to produce these effects. In particular, this
      homeodomain contains a specific lysine residue at position 9 of the recognition
      helix. Microinjected transcripts of Xotx2 constructs containing a homeodomain
      where this lysine is substituted by a glutamine or a glutamic acid residue fail
      to cause these effects.

PMID- 7720579
TI  - XIPOU 2, a noggin-inducible gene, has direct neuralizing activity.
AB  - XIPOU 2, a member of the class III POU domain family, is expressed initially in
      Spemann's organizer, and later, in discrete regions of the developing nervous
      system in Xenopus laevis. XIPOU 2 may act downstream from initial neural
      induction events, since it is activated by the neural inducer, noggin. To
      determine if XIPOU 2 participates in the early events of neurogenesis, synthetic
      mRNA was microinjected into specific blastomeres of the 32-cell stage embryo.
      Misexpression of XIPOU 2 in the epidermis causes a direct switch in cell fate
      from an epidermal to a neuronal phenotype. In the absence of mesoderm induction,
      XIPOU 2 has the ability to induce a neuronal phenotype in uncommitted ectoderm.
      These data demonstrate the potential of XIPOU 2 to act as a master regulator of
      neurogenesis.

PMID- 7720580
TI  - Regulation of Spemann organizer formation by the intracellular kinase Xgsk-3.
AB  - Dorsal axis formation in the Xenopus embryo can be induced by the ectopic
      expression of several Wnt family members. In Drosophila, the protein encoded by
      the Wnt family gene, wingless, signals through a pathway that antagonizes the
      effects of the serine/threonine kinase zeste-white 3/shaggy. We describe the
      isolation and characterization of a Xenopus homolog of zeste-white 3/shaggy, Xgsk
      3. A kinase-dead mutant of Xgsk-3, Xgsk-3K-->R, has a dominant negative effect
      and mimics the ability of Wnt to induce a secondary axis by induction of an
      ectopic Spemann organizer. Xgsk-3K-->R, like Wnt, induces dorsal axis formation
      when expressed in the deep vegetal cells, which do not contribute to the axis.
      These results indicate that the dorsal fate is actively repressed by Xgsk-3,
      which must be inactivated for dorsal axis formation to occur. Furthermore, our
      work suggests that the effects of Xgsk-3K-->R are mediated by an additional
      intercellular signal.

PMID- 7720581
TI  - Induction of the prospective neural crest of Xenopus.
AB  - The earliest sign of the prospective neural crest of Xenopus is the expression of
      the ectodermal component of Xsna (the Xenopus homologue of snail) in a low arc on
      the dorsal aspect of stage 11 embryos, which subsequently assumes the horseshoe
      shape characteristic of the neural folds as the convergence-extension movements
      shape the neural plate. A related zinc-finger gene called Slug (Xslu) is
      expressed specifically in this tissue (i.e. the prospective crest) when the
      convergence extension movements are completed. Subsequently, Xslu is found in pre
      and post-migratory cranial and trunk neural crest and also in lateral plate
      mesoderm after stage 17. Both Xslu and Xsna are induced by mesoderm from the
      dorsal or lateral marginal zone but not from the ventral marginal zone. From
      stage 10.5, explants of the prospective neural crest, which is underlain with
      tissue, are able to express Xslu. However expression of Xsna is not apparently
      specified until stage 12 and further contact with the inducer is required to
      raise the level of expression to that seen later in development. Xslu is
      specified at a later time. Embryos injected with noggin mRNA at the 1-cell stage
      or with plasmids driving noggin expression after the start of zygotic
      transcription express Xslu in a ring surrounding the embryo on the
      ventroposterior side. We suggest this indicates (a) that noggin interacts with
      another signal that is present throughout the ventral side of the embryo and (b)
      that Xslu is unable to express in the neural plate either because of the absence
      of a co-inducer or by a positive prohibition of expression. The ventral co
      inducer, in the presence of overexpressed noggin, seems to generate an
      anterior/posterior pattern in the ventral part of the embryo comparable to that
      seen in neural crest of normal embryos. We suggest that the prospective neural
      crest is induced in normal embryos in the ectoderm that overlies the junction of
      the domains that express noggin and Xwnt-8. In support of this, we show animal
      cap explants from blastulae and gastrulae, treated with bFGF and noggin express
      Xslu but not NCAM although the mesoderm marker Xbra is also expressed. Explants
      treated with noggin alone express NCAM only. An indication that induction of the
      neural plate border is regulated independently of the neural plate is obtained
      from experiments using ultraviolet irradiation in the precleavage period. At
      certain doses, the cranial crest domains are not separated into lateral masses
      and there is a reduction in the size of the neural plate.

PMID- 7720582
TI  - Germ cell nuclei of male fetal mice can support development of chimeras to
      midgestation following serial transplantation.
AB  - Chimeric embryos between fertilized eggs from F1 (C57BL x CBA) and 15.5-16.5 days
      post coitum (dpc) male fetal germ cells (FGCs) from CD-1 strain (glucose
      phosphate isomerase, Gpi-1a/a) mice were produced by nuclear transfer. Briefly, a
      single FGC was fused with enucleated oocytes and activated, and the reconstituted
      oocytes were cultured to the 2-cell stage. The nucleus from the reconstituted 2
      cell embryos was then transferred into an enucleated blastomere of the same stage
      embryos derived from F1 mice to produce chimeric embryos. The reconstituted 2
      cell embryos, which synchronously divided to the 4-cell stage after treatment
      with nocodazole, were further cultured in vitro. Compacted morula and blastocysts
      were transferred to the uteri of pseudopregnant female mice. Some recipients were
      allowed to develop to term and the others were killed at mid gestation to analyze
      the contribution of donor FGC-derived cells. Survival to term was low with no
      chimeric animals. Glucose phosphate isomerase (GPI) analysis at midgestation
      revealed that some conceptuses had chimerism in the fetuses, trophoblast and yolk
      sac at day 10.5 of pregnancy. The contribution of donor cells was 37-47%, 19-65%
      and 12-63%, respectively. It was concluded that the nucleus from 15.5-16.5 dpc
      male fetal germ cells had the potency to develop into fetus, trophoblast and yolk
      sac after serial nuclear transfer with oocytes and fertilized embryos. The reason
      for the low viability of chimeric embryos is discussed.

PMID- 7720583
TI  - Analysis of the genetic hierarchy guiding wing vein development in Drosophila.
AB  - The Drosophila rhomboid (rho) and Egf-r genes are members of a small group of
      genes required for the differentiation of various specific embryonic and adult
      structures. During larval and early pupal development expression of rho in
      longitudinal vein primordia mediates the localized formation of wing veins. In
      this paper we investigate the genetic hierarchy guiding vein development, by
      testing for genetic interactions between rho alleles and a wide variety of wing
      vein mutations and by examining the pattern of rho expression in mutant
      developing wing primordia. We identify a small group of wing vein mutants that
      interact strongly with rho. Examination of rho expression in these and other key
      vein mutants reveals when vein development first becomes abnormal. Based on these
      data and on previous genetic analyses of vein formation we present a sequential
      model for establishment and differentiation of wing veins.

PMID- 7720584
TI  - Striatal precursors adopt cortical identities in response to local cues.
AB  - One of the early steps in the regionalization of the CNS is the subdivision of
      the forebrain into dorsal and basal telencephalic ventricular zones. These
      ventricular zones give rise to the cortex and striatum respectively, in the
      mature brain. Previous work suggests that while neural precursors are able to
      move within both the dorsal cortical and basal striatal ventricular zones, they
      are unable to cross the boundary area between them. To determine if the regional
      identities of the cells in these ventricular zones are restricted, cells from the
      basal striatal ventricular zone were either transplanted back into their original
      environment or into the dorsally adjacent cortical ventricular zone. Use of in
      vitro explants of mouse telencephalon demonstrated that striatal precursors are
      able to integrate heterotopically within 12 hours of being placed onto the
      surface of cortical ventricular zone. To examine whether heterotopically placed
      neural precursors have phenotypes appropriate to their host or donor environment,
      in vivo transplants in rats were performed. Striatal ventricular zone cells
      transplanted to a striatal environment adopt morphologies and axonal projections
      characteristic of striatal cells. In contrast, striatal ventricular zone cells
      transplanted in vivo to a cortical environment acquired morphologies and axonal
      projections specific to cortex. These findings suggest that within forebrain,
      position-specific cues play an instructive role in determining critical aspects
      of regional phenotype.

PMID- 7720585
TI  - A role for HGF/SF in neural induction and its expression in Hensen's node during
      gastrulation.
AB  - It was previously shown (Roberts, C., Platt, N., Streit, A., Schachner, M. and
      Stern, C. D. (1991) Development 112, 959-970) that grafts of Hensen's node into
      chick embryos enhanced and maintain expression of the L5 carbohydrate in
      neighbouring epiblast cells, and that antibodies against L5 inhibit neural
      induction by such a graft. We now show that L5 is initially widely expressed in
      the epiblast, but as neural induction proceeds it gradually becomes confined to
      and up-regulated in the early neural plate. L5 can therefore be considered as a
      marker for cells that are competent to respond to neural induction. We also show
      that Hepatocyte Growth Factor/Scatter Factor (HGF/SF) promotes the expression of
      L5 by extraembryonic epiblast in collagen gels after overnight culture. Explants
      cultured for several days in the presence of HGF/SF, as well as explants of
      prospective neural plate, can differentiate into cells with neuronal morphology
      expressing neuronal markers. To investigate whether HGF/SF is expressed in the
      chick embryo at appropriate stages of development, we produced specific cDNA
      probes and used them for in situ hybridization. We find that at the primitive
      streak stage, HGF/SF is expressed specifically in Hensen's node. We therefore
      propose that HGF/SF plays a role during the early steps of neural induction,
      perhaps by inducing or maintaining the competence of the epiblast to respond to
      neural inducing signals.

PMID- 7720586
TI  - Retinoic acid stage-dependently alters the migration pattern and identity of
      hindbrain neural crest cells.
AB  - This study investigates the migration patterns of cranial neural crest cells in
      retinoic acid (RA)-treated rat embryos using DiI labeling. Wistar-Imamichi rat
      embryos were treated at the early (9.0 days post coitum, d.p.c.) and late (9.5
      d.p.c.) neural plate stages with all-trans RA (2 x 10(-7) M) for 6 hours and
      further cultured in an RA-free medium. RA exposure stage dependently induced two
      typical craniofacial abnormalities; that is, at 9.0 d.p.c. it reduced the size
      and shape of the first branchial arch to those of the second arch, whereas, in
      contrast, at 9.5 d.p.c. it induced fusion of the first and second branchial
      arches. Early-stage treatment induced an ectopic migration of the anterior
      hindbrain (rhombomeres (r) 1 and 2) crest cells; they ectopically distributed in
      the second branchial arch and acousticofacial ganglion, as well as in their
      original destination, i.e., the first arch and trigeminal ganglion. In contrast,
      late-stage treatment did not disturb the segmental migration pattern of hindbrain
      crest cells even though it induced the fused branchial arch (FBA); labeled crest
      cells from the anterior hindbrain populated the anterior half of the FBA and
      those from the preotic hindbrain (r3 and r4) occupied its posterior half. In
      control embryos, cellular retinoic acid binding protein I (CRABP I) was strongly
      expressed in the second branchial arch, r4 and r6, while weakly in the first arch
      and r1-3. CRABP I was upregulated by the early-stage treatment in the first
      branchial arch and related rhombomeres, while its expression was not
      correspondingly changed by the late-stage treatment. Moreover, whole-mount
      neurofilament staining showed that, in early-RA-treated embryos, the typical
      structure of the trigeminal ganglion vanished, whereas the late-stage-treated
      embryos showed the feature of the trigeminal ganglion to be conserved, although
      it fused with the acousticofacial ganglion. Thus, from the standpoints of
      morphology, cell lineages and molecular markers, it seems likely that RA alters
      the regional identity of the hindbrain crest cells, which may correspond to the
      transformation of the hindbrain identity in RA-treated mouse embryos (Marshall et
      al., Nature 360, 737-741, 1992).

PMID- 7720587
TI  - The mouse homolog of the orphan nuclear receptor tailless is expressed in the
      developing forebrain.
AB  - The Drosophila tailless gene is a member of the orphan nuclear receptor
      subfamily. In Drosophila, the tailless gene is required for pattern formation in
      embryonic poles. During development, tailless is activated in the termini of the
      embryo in response to the torso receptor tyrosine kinase signal transduction
      cascade. Recessive mutations of tailless result in abnormalities in anterior
      portions of the head and in all structures posterior to the eighth abdominal
      segment. Localised expression of tailless is required in combination with a
      second terminal gene, huckebein, to control the expression of downstream genes.
      We have isolated a mouse homolog of the Drosophila tailless gene, which shows
      considerable homology in the DNA-binding domain suggesting that the respective
      proteins bind similar recognition sequences. Although the ligand-binding domain
      shows features in common with the tailless ligand domain, it also shares
      conserved amino acid stretches with other orphan nuclear receptors, the human
      ovalbumin upstream binding protein transcription factors (hCOUP-TF I and II). We
      have analysed the expression of taillees in mice, and show that it is
      specifically localised to the developing forebrain from day 8 p.c. and in dorsal
      midbrain from day 8.75 p.c. To define the anterior and posterior boundaries of
      expression, we compared the expression pattern of tailless to those of other
      forebrain markers, including distal-less (Dlx1), brain factor 1 (BF1), and the
      orthodenticle genes (Otx1 and Otx2). In addition to the developing forebrain,
      these genes show dynamic patterns of expression in two structures whose
      development requires inductive signals from the forebrain: the eye and the nose.
      These results suggest that the mouse taillees gene may be required to pattern
      anterior brain differentiation.

PMID- 7720588
TI  - Serrate expression can functionally replace Delta activity during neuroblast
      segregation in the Drosophila embryo.
AB  - Serrate and Delta encode structurally related proteins in D. melanogaster that
      bind within a common extracellular region on the NOTCH receptor molecule. We used
      ectopic expression to determine if SERRATE could mediate in vivo functions
      parallel or antagonistic to those proposed for the putative NOTCH ligand DELTA.
      Our results demonstrate that Serrate can replace Delta gene function during
      embryonic neuroblast segregation and that expression of Serrate leads to a NOTCH
      dependent suppression of achaete expression in proneural clusters. Our findings
      strongly suggest that SERRATE functions as an alternative ligand capable of NOTCH
      activation.

PMID- 7720589
TI  - Repression of Pax-2 by WT1 during normal kidney development.
AB  - The developmental, regulatory gene Pax-2 is activated during early kidney
      morphogenesis and repressed in mature renal epithelium. Persistent Pax-2
      expression is also observed in a variety of kidney tumors. Yet, little is known
      about the signals regulating this transient expression pattern in the developing
      kidney. We have examined the spatial and temporal expression patterns of Pax-2
      and the Wilm's tumor suppresser protein WT1 with specific antibodies in
      developing mouse kidneys. A marked increase in WT1 protein levels coincided
      precisely with down-regulation of the Pax-2 gene in the individual precursor
      cells of the visceral glomerular epithelium, suggesting a direct effect of the
      WT1 repressor protein on Pax-2 regulatory elements. To examine whether WT1 could
      directly repress Pax-2 transcription, binding of WT1 to three high affinity sites
      in the 5' untranslated Pax-2 leader sequence was demonstrated by DNAseI
      footprinting analysis. Furthermore, co-transfection assays using CAT reporter
      constructs under the control of Pax-2 regulatory sequences demonstrated WT1
      dependent transcriptional repression. These three WT1 binding sites were also
      able to repress transcription, in a WT1-dependent manner, when inserted between a
      heterologous promoter and the reporter gene. The data indicate that Pax-2 is a
      likely target gene for WT1 and suggest a direct link, at the level of
      transcriptional regulation, between a developmental control gene, active in
      undifferentiated and proliferating cells, and a known tumor suppressor gene.

PMID- 7720590
TI  - The T gene is necessary for normal mesodermal morphogenetic cell movements during
      gastrulation.
AB  - The T (Brachyury) deletion in mouse is responsible for defective primitive streak
      and notochord morphogenesis, leading to a failure of the axis to elongate
      properly posterior to the forelimb bud. T/T embryonic stem (ES) cells colonise
      wild-type embryos, but in chimeras at 10.5 days post coitum (dpc) onwards they
      are found predominantly in the distal tail, while trunk paraxial and lateral
      mesoderm are deficient in T/T cells (Wilson, V., Rashbass, P. and Beddington, R.
      S. P. (1992) Development 117, 1321-1331). To determine the origin of this
      abnormal tissue distribution, we have isolated T/T and control T/+ ES cell clones
      which express lacZ constitutively using a gene trap strategy. Visualisation of
      T/T cell distribution in chimeric embryos throughout gastrulation up to 10.5 dpc
      shows that a progressive buildup of T/T cells in the primitive streak during
      gastrulation leads to their incorporation into the tailbud. These observations
      make it likely that one role of the T gene product is to act during gastrulation
      to alter cell surface (probably adhesion) properties as cells pass through the
      primitive streak. As the chimeric tail elongates at 10.5 dpc, abnormal morphology
      in the most distal portion becomes apparent. Comparison of T expression in the
      developing tailbud with the sites of accumulation of T/T cells in chimeras shows
      that T/T cells collect in sites where T would normally be expressed. T expression
      becomes internalised in the tailbud following posterior neuropore closure while,
      in abnormal chimeric tails, T/T cells remain on the surface of the distal tail.
      We conclude that prevention of posterior neuropore closure by the wedge of T/T
      cells remaining in the primitive streak after gastrulation is one source of the
      abnormal tail phenotypes observed. Accumulation of T/T cells in the node and
      anterior streak during gastrulation results in the preferential incorporation of
      T/T cells into the ventral portion of the neural tube and axial mesoderm. The
      latter forms compact blocks which are often fused with the ventral neural tube,
      reminiscent of the notochordal defects seen in intact mutants. Such fusions may
      be attributed to cell-autonomous changes in cell adhesion, possibly related to
      those observed at earlier stages in the primitive streak.

PMID- 7720591
TI  - Differential regulation of transcription factor gene expression and phenotypic
      markers in developing sympathetic neurons.
AB  - We have examined the regulation of transcription factor gene expression and
      phenotypic markers in developing chick sympathetic neurons. Sympathetic
      progenitor cells first express the bHLH transcriptional regulator Cash-1 (a
      chicken achaete-scute homologue), followed by coordinate expression of Phox2, a
      paired homeodomain protein, and GATA-2, a zinc finger protein. SCG10, a pan
      neuronal membrane protein, is first detected one stage later, followed by the
      catecholaminergic neurotransmitter enzyme tyrosine hydroxylase (TH). We have used
      these markers to ask two questions: (1) is their expression dependent upon
      inductive signals derived from the notochord or floor plate?; (2) does their
      sequential expression reflect a single linear pathway or multiple parallel
      pathways? Notochord ablation experiments indicate that the floor plate is
      essential for induction of GATA-2, Phox2 and TH, but not for that of Cash-1 and
      SCG10. Taken together these data suggest that the development of sympathetic
      neurons involves multiple transcriptional regulatory cascades: one, dependent
      upon notochord or floor plate-derived signals and involving Phox2 and GATA-2, is
      assigned to the expression of the neurotransmitter phenotype; the other,
      independent of such signals and involving Cash-1, is assigned to the expression
      of pan-neuronal properties. The parallel specification of different components of
      the terminal neuronal phenotype is likely to be a general feature of neuronal
      development.

PMID- 7720592
TI  - A dominant inhibitory version of the small GTP-binding protein Rac disrupts
      cytoskeletal structures and inhibits developmental cell shape changes in
      Drosophila.
AB  - The Rho subfamily of Ras-related small GTP-binding proteins is involved in
      regulation of the cytoskeleton. The cytoskeletal changes induced by two members
      of this subfamily, Rho and Rac, in response to growth factor stimulation, have
      dramatic effects on cell morphology. We are interested in using Drosophila as a
      system for studying how such effects participate in development. We have
      identified two Drosophila genes, DRacA and DRacB, encoding proteins with homology
      to mammalian Rac1 and Rac2. We have made transgenic flies bearing dominant
      inhibitory (N17DRacA), and wild-type versions of the DRacA cDNA under control of
      an Hsp70 promoter. Expression of the N17DRacA transgene during embryonic
      development causes a high frequency of defects in dorsal closure which are due to
      disruption of cell shape changes in the lateral epidermis. Embryonic expression
      of N17DRacA also affects germband retraction and head involution. The epidermal
      cell shape defects caused by expression of N17DRacA are accompanied by disruption
      of a localized accumulation of actin and myosin thought to be driving epidermal
      cell shape change. Thus the Rho subfamily may be generating localized changes in
      the cytoskeleton during Drosophila development in a similar fashion to that seen
      in mammalian and yeast cells. The Rho subfamily is likely to be participating in
      a wide range of developmental processes in Drosophila through its regulation of
      the cytoskeleton.

PMID- 7720593
TI  - Avian neural crest cells can migrate in the dorsolateral path only if they are
      specified as melanocytes.
AB  - Neural crest cells are conventionally believed to migrate arbitrarily into
      various pathways and to differentiate according to the environmental cues that
      they encounter. We present data consistent with the notion that melanocytes are
      directed, by virtue of their phenotype, into the dorsolateral path, whereas other
      neural crest derivatives are excluded. In the avian embryo, trunk neural crest
      cells that migrate ventrally differentiate largely into neurons and glial cells
      of the peripheral nervous system. Neural crest cells that migrate into the
      dorsolateral path become melanocytes, the pigment cells of the skin. Neural crest
      cells destined for the dorsolateral path are delayed in their migration until at
      least 24 hours after migration commences ventrally. Previous studies have
      suggested that invasion into the dorsolateral path is dependent upon a change in
      the migratory environment. A complementary possibility is that as neural crest
      cells differentiate into melanocytes they acquire the ability to take this
      pathway. When quail neural crest cells that have been grown in culture for 12
      hours are labeled with Fluoro-gold and then grafted into the early migratory
      pathway at the thoracic level, they migrate only ventrally and are coincident
      with the host neural crest. When fully differentiated melanocytes (96 hours old)
      are back-grafted under identical conditions, however, they enter the dorsolateral
      path and invade the ectoderm at least one day prior to the host neural crest.
      Likewise, neural crest cells that have been cultured for at least 20 hours and
      are enriched in melanoblasts immediately migrate in the dorsolateral path, in
      addition to the ventral path, when back-grafted into the thoracic level. A
      population of neural crest cells depleted of melanoblasts--crest cells derived
      from the branchial arches--are not able to invade the dorsolateral path,
      suggesting that only pigment cells or their precursors are able to take this
      migratory route. These results suggest that as neural crest cells differentiate
      into melanocytes they can exploit the dorsolateral path immediately. Even when 12
      hour crest cells are grafted into stage 19-21 embryos at an axial level where
      host crest are invading the dorsolateral path, these young neural crest cells do
      not migrate dorsolaterally. Conversely, melanoblasts or melanocytes grafted under
      the same circumstances are found in the ectoderm. These latter results suggest
      that during normal development neural crest cells must be specified, if not
      already beginning to differentiate, as melanocytes in order to take this
      path.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7720594
TI  - [A breakthrough in solving the genetic background of colon cancer].

PMID- 7720595
TI  - [Acoustic trauma].

PMID- 7720596
TI  - [Inflammatory muscle diseases].

PMID- 7720597
TI  - [PAP Class II in gynecology].

PMID- 7720598
TI  - [Magnetic spectroscopy--a new method for studying the brain].

PMID- 7720600
TI  - [All-trans-retinoic acid in the treatment of promyelocytic leukemia].

PMID- 7720599
TI  - [Suicide methods in Finland: does availability and restrictions have an effect on
      number of suicides?].

PMID- 7720601
TI  - [Low blood pressure, shock and unconsciousness in a young woman].

PMID- 7720602
TI  - [Sudden hearing loss--a mysterious treatment of a mysterious disease].

PMID- 7720603
TI  - [Smoking and weight].

PMID- 7720604
TI  - [Electroretinography].

PMID- 7720605
TI  - [Catheter ablation in supraventricular tachycardia].

PMID- 7720606
TI  - [Frequency of reoperations in cleft palate as an indicator of quality of
      surgery].

PMID- 7720607
TI  - [Anaphylactic reaction associated with rubber allergy during barium enema
      studies].

PMID- 7720608
TI  - [How should one react to a murder threat?].

PMID- 7720609
TI  - [Progressive neurological findings and lymphadenopathy in a young woman].

PMID- 7720610
TI  - ["RR 160/80" Scipione Riva-Rocci (1863-1937)].

PMID- 7720611
TI  - [Finnish cholesterol discussion].

PMID- 7720612
TI  - [Action should be taken in measuring quality of life].

PMID- 7720613
TI  - [Health care and quality of life].

PMID- 7720614
TI  - [Experience and observed quality of life--complementary viewpoints].

PMID- 7720615
TI  - [Measurement of quality of life in various diseases].

PMID- 7720616
TI  - [Theory of measurements and practice].

PMID- 7720617
TI  - [Social phobia: clinical and therapeutic approach].
AB  - Although social phobia is a real pathological condition, it has often been
      neglected. In fact, social phobia is among the least studies of the major anxiety
      disorders. This is quite surprising, as approximately 2% of the population suffer
      from debilitating social phobia with devastating effects on career and quality of
      life, and as this disorder can now be considered as a treatable condition. After
      defining social phobia, the authors will describe the prevalence, clinical
      features and etiology of social phobia. Effective psychopharmacological and
      psychological treatments of social phobia will also be reviewed. The drugs that
      have been most studied are monoamine oxidase inhibitors and beta-blockers.
      Several controlled studies have also concluded that behavioral and cognitive
      therapies (exposure in vivo therapy, social skills training, cognitive
      restructuring) are beneficial for social phobics. The combination of
      psychopharmacotherapy and psychological interventions also seems promising.
      Finally, as it is necessary to distinguish among various subtypes of social
      phobia, further studies will have to investigate whether specific subtypes do
      better or worse with specific treatments.

PMID- 7720618
TI  - [Social phobia: historical and conceptual perspectives].
AB  - Social phobia is individualized in international classifications only since 1980
      with the DSM III, ten years after the publication by Marks of its phobic
      disorders classification. Nevertheless, many european authors, psychiatrists or
      psychologists, have raised the question of social anxiety as far back as the
      eighteenth century, with various points of view and appellations. The first
      report of an ereutophobia observation is due to Casper, in 1846, which described
      a serious social anxiety affecting a young man. Ereutophobia has been especially
      studied by Pitres and Regis, in 1807 and 1902, and by Claparede in a
      comprehensive review published in the same period. Janet has also proposed, in
      1903, a classification of phobia including a section for social phobia. In 1910,
      Hartenberg has described several forms of social anxiety under the generic term
      of shyness (timidity, performance anxiety, personality disorders, etc.). Then,
      there is a relative silent period until 1960 even if the names of Kontaktneurosen
      or social neurosis are punctually mentioned in british and german literatures,
      and if Morita, in Japan, has taken an interest in social anxiety around 1930. The
      existence of social phobia as a valid syndrome A has been confirmed in the
      successive classifications since the DSM III. Several structured interview
      schedules or self-rating scales have been proposed for assessment of social
      phobia, such as Liebowitz or Davidson scales, but at present no one instrument
      has demonstrated superiority and the use of a battery of several scales is
      recommended. Moreover, some diagnostic issues are not yet completely solved, in
      particular concerning the validity of different subtypes of social phobia. To
      date, only the generalized type has been individualized in the classifications
      when circumscribed and performance types remain disputed. Delineation of social
      phobia with avoidant personality, shyness, performance and test anxiety, other
      phobic disorders and complications like alcoholism are discussed. Clinical,
      epidemiological and therapeutical implications of these questions are of
      importance from a theoretical but also practical point of view.

PMID- 7720619
TI  - [Psychometric evaluation of depression in the elderly subject: which instruments?
      What are the future perspectives?].
AB  - Depression in the elderly is frequent but often unknown (in 30 to 50% of the
      cases) because of difficulties in detecting or diagnosing it. This is due to the
      clinical features and prognosis of depression in this kind of population but also
      to the non-existence of specific diagnostic tests. Most of the authors consider
      that the most useful diagnostic tests are screening assessments. Some are rating
      scales that have been validated in general population then secondarily in the
      elderly: Hamilton Rating Depression Scale (HDRS), Montgomery & Asberg Depression
      Rating Scale (MADRS), Zung Self Rating Depression Scale (Zung SDS), Beck
      Depression Inventory (BDI) or Center for Epidemiological Studies Depression Scale
      (CES-D). They usually involve biases linked to age and more particularly to
      somatic items; and the educational level required to answer is too high for this
      population. However, the MADRS is still interesting for measuring change under
      treatment and the CES-D for detection of depressive elderly. On the other hand,
      some screening scales are specific of depression in the elderly. The most
      commonly used is the GDS (Geriatric Depression Scale) with 30 items. Some points
      have been discussed to increase the achievement of these methods. For example,
      inventories are better than interviews and should be integrated into semi
      standardized interviews which do not last more than 30 minutes. The quotation
      'yes' or 'no' is preferable. The instrument have to be short but have to contain
      specific items for depression in the elderly. Several short forms are already
      validated or in progress such as GDS with 15 items and, recently, with 4 items,
      BASDEC, short Zung IDS, BDI with 13 items and DGDS. However, these screening
      scales loose a part of their validity in the moderate or severe demented elderly.
      Few instruments can screen depression in a demented population although
      depression and dementia syndromes are frequently associated. Some of the
      inventories used are not specific: they evaluate the general psychopathology in
      the elderly and contains subscales which screen depression or organic brain
      disease. Thus, GMS-AGECAT Package, CAMDEX, CARPER, BAS are often used by the
      Anglo-Saxons. At present, only one specific instrument has been validated: the
      Cornell Scale for Depression in Dementia. Recently, new screening instruments
      have been put forward: Dementia Mood Assessment Scale and Canberra Interview for
      the elderly which seem interesting but need further studies.

PMID- 7720620
TI  - [Value and limits of a statistical aid in typological constructions].
AB  - Correspondence analysis has become the favoured method to describe qualitative
      data. Graphical representation allows to appreciate positions of different
      modalities between them and in relation with the two factorial design axis.
      Nevertheless, lecture and interpretation seem to depend on the researcher's
      assessment who doesn't know always how modalities are jointed. Tri-Deux
      statistical software directly makes this level readable. Developed by a
      sociologist engineer from the CNRS, it is free of charge and operates with PC or
      compatible material. Every time a modality is in attraction with an other (on the
      basis of independency deviations), one line links the two points: this tool
      permits to visualize how modalities of analysed variables gather or contrast
      together. All the connections are not equal, some of them are more important than
      others. This program allows to draw each connection with a decreasing order
      according to their weight and to distinguish the highest attractions from the
      lowest ones. An example with a study allows to understand interest of this
      method. The aim of this statistical way is researching a possible typology in the
      analysed corpus. It is necessary to outline, in this method, the significance of
      an empirical phase when deliverate research of disconnected graphical complexes
      (clinical entities) leads to rule out non discriminant variables. Analysis
      consists to study data according to their clinical relevance and to their dynamic
      cohesion. This time corresponds to a real 'come back to the clinical
      practice'.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720621
TI  - [Suicide in Paris and Ile-de-France].
AB  - A study carried out in collaboration between the Institute of Forensic Medicine
      of Paris and the INSERM (SC8) concerned all the suicide occurred in Paris region
      over 1990; 455 suicides in Paris and 1,229 in the suburbs of Paris (overall,
      1,684 suicides observed in Paris area for the same period). For Paris city, the
      rate of suicide reaches 23.3 per 100,000 subjects. This frequency increases up to
      40 years and falls after this age with a further rise between 75 and 85 years.
      Suicide represents 17% of the total mortality for adolescents and young adults
      living in Paris, with a large over-representation of males (277 males, 178
      females). Suicide is more frequent before 45 years in Paris than in France but
      this tendency is reversed after 45 years. It represents the first cause of
      violent deaths among young population (15-34 years) living in Paris and is, after
      AIDS, the second cause of death. In Paris suburbs, it constitutes the second
      cause of mortality after traffic accidents. The mode of suicide in Paris is
      essentially poisoning, then hanging and jumping from high place. In contrast,
      outside Paris, the hanging is more frequently used than poisoning and firearms.
      The contribution of the Institute of Forensic Medicine of Paris is essential for
      the knowledge of these voluntary deaths, a large part of them being unknown in
      the National statistic of causes of death. This underestimation is extremely
      important: only 68% of the suicides are known by the Official Statistic in Paris
      region and 26% for Paris city.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720622
TI  - [Obsessive-compulsive disorder in the child and adolescent: developmental aspects
      and therapeutic strategies].
AB  - The obsessive-compulsive disorder has only recently been recognized as a specific
      pathological entity in children, despite the fact that the first descriptions of
      pediatric manifestations date back to the beginning of this century (P. Janet,
      1903) with further reports having been published regularly since that time. The
      first assessment of the complete epidemiologic, clinical and functional
      repercussions of the obsessive-compulsive disorder was reported by the Pediatric
      Psychiatric Group of the NIMH (Pr Judith Rapoport); of their various
      publications, one is well known in France: The Child who Couldn't Stop Washing
      (17). Among possible reasons for this delayed recognition are the special
      conditions for diagnosis and the frequent underestimation of its importance by
      the family, and sometimes by doctors. This underassessment could be due to
      confusion between the normal developmental rituals which are frequently seen
      between the ages of 3 and 5 years, and which do not cause any particular
      handicaps, and a more severe symptomatology which interferes with normal academic
      and social adaptation, presenting a substantially worse long-term prognosis.
      Having recognized the disorder, questions have arisen as to its possible linkage
      with the form seen in adults. There are numerous convergent argument suggesting a
      certain long-term persistence of this disorder throughout development and later
      life: 1) the relative stability of the incidence and prevalence of the disorder;
      2) phenomenologic and developmental similarities; 3) most recently, comparable
      efficacy of treatments for pediatric and adult obsessive-compulsive disorder,
      whether by the behavioral modification approaches or by pharmacologic treatment,
      notably with the serotonin re-uptake inhibitors (clomipramine, fluoxetine,
      fluvoxamine).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720623
TI  - [Effect of antidepressant treatment on sense of dyscontrol: preliminary studies].
AB  - Cumulative data in the field of phenomenology, neurobiology and
      psychopharmacology indicate "discontrol" as a dimension probably linked to
      serotonin central activity and frequently observed in major depression and other
      related disorders. A new questionnaire for evaluating this dimension is proposed:
      Behavioral Discontrol Scale (BDS). The BDS was constructed in 1990 and validated
      through multiple clinical studies: the first validation study included 166
      patients (subdivided in 4 subgroups, anxious, depressed, alcohol abusers and
      bulimics fulfilling DSM III-R criteria) and 35 controls. The second validation
      study concerned a large clinical population suffering from major depression
      according tho DSM III-R criteria (n = 1360 patients). The episodes classified as
      psychogenic or neurotic and characterised as "agitated, anxious, impulsive and/or
      suicidal"' showed the highest scores on discontrol (p < 0.001). Following these
      initial studies, the present study was conducted to evaluate prospectively the
      sensitivity of BDS to change under different antidepressant treatments
      (serotonergic versus other agents). Preliminary data were obtained within a group
      of 62 outpatients suffering from major depression (DSM III-R criteria), treated
      naturalisticly and followed on a 4 weeks period. Results showed that discontrol
      is sensitive to change, especially in the fluoxetine group (decrease at day 28 by
      35% vs 23% and 24% in other groups, p = 0.17). Changes of discontrol scores was
      shown to be related to benzodiazepine (BZD) combination to antidepressant
      treatment. In fact, in the group "with BZD" (n = 42), the magnitude of BDS score
      variation was less important than in the group "without BZD" (n = 19):
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720624
TI  - [Spontaneous orgasms induced by amineptine].

PMID- 7720625
TI  - Even with extensive molecular insight, we can be blind when it comes to the
      animal.

PMID- 7720626
TI  - Corticotropin-releasing factor alone, but not arginine vasopressin alone,
      stimulates the release of adrenocorticotropin in the conscious intact sheep.
AB  - These studies compared the relative potencies of CRF and arginine vasopressin
      (AVP) as ACTH secretagogues in the sheep. Dose-response curves to CRF (10, 25,
      50, and 100 micrograms/h) and AVP (0.3, 1.0, 3.0, and 10.0 micrograms/h) were
      obtained in five adult sheep, with arterial blood samples taken for CRF, AVP,
      ACTH, and cortisol measurements to determine the pituitary-adrenal response. It
      was found that the first dose of CRF increased plasma CRF levels to 444 +/- 79
      pg/ml. ACTH levels rose significantly from 28 +/- 5 to 186 +/- 46 pg/ml, with a
      concurrent rise in cortisol levels from 7 +/- 3 to 44 +/- 9 ng/ml. Although
      plasma ACTH and cortisol levels remained elevated, higher doses of CRF failed to
      produce further increases. AVP, at all of the doses studied, did not produce an
      increase in ACTH levels, although cortisol levels rose significantly by the
      second dose. In a second series of experiments, animals received a continuous
      infusion of CRF (10 micrograms/h) alone or in combination with graded doses of
      AVP (0.3, 1.0, 3.0, and 10.0 micrograms/h for 60 min each). It was found that AVP
      at the highest dose was able to potentiate the ACTH response to CRF. Lower doses
      of AVP, which did not stimulate a further increase in ACTH levels were, however,
      associated with a significant rise in cortisol levels. In conclusion, it was
      found that although CRF alone was a potent stimulator of ACTH secretion, AVP at
      the doses studied was not able to elicit an ACTH response in the conscious intact
      sheep. However, a dose of AVP that was not stimulatory in itself was able to
      augment the ACTH response to CRF.

PMID- 7720627
TI  - Signaling properties of mouse and human corticotropin-releasing factor (CRF)
      receptors: decreased coupling efficiency of human type II CRF receptor.
AB  - CRF is the primary neuroregulator of the function of the hypothalamic-pituitary
      adrenal axis. We have recently cloned a mouse CRF receptor (mCRF-R) complementary
      DNA (cDNA) from an AtT-20 cell cDNA library by polymerase chain reaction. To
      compare the functions of mCRF-R to those of the human type I and type II CRF
      receptors (hCRF-RI and hCRF-RII), cDNAs were cloned into the expression vector
      pcDNA1 and transfected into COS-7 cells. CRF binding and CRF-stimulated cAMP
      accumulation as well as phosphoinositide hydrolysis were measured. Scatchard
      analysis of the binding of 125I-labeled [Tyr0]r/hCRF ([125I]CRF) to COS-7 cells
      expressing mCRF-R and hCRF-RI cDNAs revealed the same apparent Kd (9 nM). In
      contrast, the apparent binding Kd for hCRF-RII was 20 nM CRF. Maximal stimulatory
      concentrations (1 microM) of rat/human CRF-(1-41) (r/hCRF) increased cAMP
      accumulation in COS-7 cells transfected with mCRF-R, hCRF-RI, and hCRF-RII cDNA
      plasmid (10 micrograms each) from basal values of 8-19 pmol/10(5) cells.15 min to
      84 +/- 10, 87 +/- 16, and 45 +/- 16 pmol/10(5) cells.15 min, respectively. The
      EC50 values of r/hCRF-stimulated cAMP accumulation in COS-7 cells expressing mCRF
      R and hCRF-RI cDNAs were similar at 0.4 +/- 0.2 and 0.7 +/- 0.2 nM, respectively.
      Conversely, the EC50 of r/hCRF-stimulated cAMP accumulation in hCRF-RII
      transfected COS-7 cells was 47.5 +/- 18.9 nM. As the level of expression of hCRF
      RII was lower than that of hCRF-RI, we compared r/hCRF-stimulated cAMP
      accumulation in COS-7 cells expressing low and high levels of hCRF-RI. The EC50
      for r/hCRF-stimulated cAMP accumulation in COS-7 cells transfected with hCRF-RI
      did not change when receptor expression was varied by a factor of 1- to 8.4-fold.
      In contrast, the EC50 for r/hCRF-stimulated cAMP accumulation mediated by hCRF
      RII was at least 100-fold higher than that mediated by the hCRF-RI in COS-7
      cells, which suggests poor coupling between hCRF-RII and adenylate cyclase.
      Inositol phosphate (IP) levels were also determined in mCRF-R, hCRF-RI, and hCRF
      RII cDNA-transfected COS-7 cells stimulated with increasing concentrations of
      r/hCRF. r/hCRF-stimulated IPs accumulation was dose dependent in COS-7 cells
      expressing mCRF-R and hCRF-RI using 100 and 1000 nM r/hCRF. Concentrations of 10
      (or less) nM r/hCRF had no effect on IP generation. hCRF-RII did not mediate
      stimulation of IP even at 1000 nM r/hCRF.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7720629
TI  - Ontogeny of growth hormone (GH)-secreting cells during chicken embryonic
      development: initial somatotrophs are responsive to GH-releasing hormone.
AB  - In the present study, a reverse hemolytic plaque assay (RHPA) for chicken GH was
      established and used to study the ontogeny of somatotroph differentiation and
      functional responsiveness to GH-releasing hormone (GHRH) during chicken embryonic
      development. Anterior pituitaries from embryos on days 10, 12, 14, and 16 of
      incubation were isolated and dissociated into single cells with trypsin. The
      resulting cells were then subjected to the GH plaque assay under basal and GHRH
      stimulated conditions. No GH-releasing cells were detected on day 10 or 12 of
      embryonic development. In contrast, a few somatotrophs (< 2% of all cells) were
      consistently found on day 14, and a statistically significant population existed
      on day 16, when 6.3 +/- 1.4% of all anterior pituitary cells secreted GH. Thus,
      GH-secreting cells differentiated by embryonic day 16. Treatment of pituitary
      cells from day 16 embryos with GHRH was found to increase the proportion of GH
      plaque-forming cells during a shortened assay interval from 1.8 +/- 0.3% under
      basal conditions to 6.7 +/- 1.2% in the presence of GHRH. This nearly 4-fold
      increase in the proportion of plaque-forming cells indicates that at least 70% of
      the initial somatotrophs present on day 16 were responsive to the stimulatory
      effects of GHRH. To test whether the absence of GH cells on day 12 of embryonic
      development was due to the presence of cells that produced but did not release
      GH, pituitary cells from day 12 and day 16 embryos were subjected to
      immunocytochemistry for GH and to the GH RHPA in parallel. No significant
      differences were found in the percentage of cells that either contained or
      released GH on the two embryonic ages tested. On day 12, 1.1 +/- 0.8% of all
      cells contained GH, as determined by immunocytochemistry, whereas 0.5 +/- 0.5%
      released GH as determined by RHPA. By day 16, the proportions of cells that
      contained and released GH had increased to 9.5 +/- 0.6 and 11.2 +/- 2.5%,
      respectively. Taken together, these results indicate that GH-secreting cells
      differentiate by day 16 of chicken embryonic development and that these initial
      somatotrophs are responsive to GHRH. Given that growth and metabolism are
      regulated in part by GH in chick embryos, these findings suggest that these
      processes may be under hypothalamic control during late embryonic development in
      the chicken.

PMID- 7720628
TI  - Age-related changes in peptide-23/pancreatitis-associated protein and pancreatic
      stone protein/reg gene expression in the rat and regulation by growth hormone
      releasing hormone.
AB  - Peptide-23 is a 16-kilodalton protein secreted by rat pituitary cells that was
      first identified because it was regulated by GRF and somatostatin in a similar
      fashion to GH. Cloning of peptide-23 complementary DNA revealed that it is
      identical to pancreatitis-associated protein (PAP) and a member of the c-lectin
      gene family. We examined the expression of peptide-23/PAP and a structurally
      related protein, pancreatic stone protein (PSP/reg), in the rat gastrointestinal
      tract. Here we report age-related changes in the expression and GRF regulation of
      peptide-23. Both peptide-23/PAP messenger RNA (mRNA) and PSP/reg mRNA were
      virtually undetectable in the small intestine of newborn and 1- and 2-week-old
      rats. A dramatic increase in the expression of both genes was seen at the time of
      weaning in the third week postpartum. The abundance of both of these mRNA
      decreases after 3 and 6 months of age. Peptide-23/PAP mRNA is most abundant in
      the ileum, whereas PSP/reg is maximally expressed in the pancreas and duodenum.
      Human GRF analog pellets were implanted sc into adult male rats for 2 weeks to
      study the chronic effects of GRF on the expression of these genes. Both peptide
      23/PAP and PSP/reg mRNA levels in duodenum and jejunum were increased in these
      rats compared with levels in control rats. However, no increase in peptide-23/PAP
      mRNA in response to GRF treatment was seen in the ileum, where the level of
      expression of this gene is very high, and GRF had no effect on peptide-23/PSP
      expression in the heart, pituitary, or hypothalamus, where expression is normally
      undetectable. In situ hybridization was used to localize peptide-23/PSP in the
      small intestine and pancreas of GRF-treated rats. An increase in peptide-23/PAP
      mRNA was restricted to acinar cells close to islets, whereas little expression
      was seen in acinar cells distant from islets, suggesting that either peptide
      23/PAP may have some paracrine action on the islets, or alternatively, an islet
      derived factor may function as a paracrine modulator of peptide-23/PAP
      expression. These data demonstrate that GRF modulates peptide-23/PAP expression
      in the gastrointestinal tract in a similar fashion to that previously reported
      for pituitary cells in primary culture.

PMID- 7720630
TI  - Time course of action of pertussis toxin to block the inhibition of stimulated
      insulin release by norepinephrine.
AB  - Male Sprague-Dawley rats were injected ip with 1 microgram pertussis toxin
      (PTX)/100 g BW. The rats were killed 24, 48, and 72 h after injection, and their
      pancreases were removed. At each time point, insulin secretion by isolated islets
      was measured under basal and glucose-stimulated conditions and in the absence and
      presence of norepinephrine. cAMP levels were measured under basal and forskolin
      stimulated conditions in the absence and presence of norepinephrine. PTX-induced
      ADP ribosylation of Gi/Go proteins in vivo was monitored by ADP ribosylation in
      vitro using PTX and 32P-labeled NAD and also by Western blotting. At 24 h, 1
      microM norepinephrine inhibited glucose-stimulated insulin secretion by 92% in
      the control islets, but by only 53% in the PTX-treated islets; at 48 h,
      norepinephrine still inhibited secretion (by 40%) in the PTX-treated islets; at
      72 h, the inhibitory effect of norepinephrine was abolished. Therefore, contrary
      to recent suggestions, all of the effect of norepinephrine to inhibit insulin
      release is PTX sensitive. The effects of PTX on the ability of norepinephrine to
      lower cAMP levels were similar to those observed for the inhibition of insulin
      release. PTX partially blocked the effect of norepinephrine to lower cAMP levels
      at 24 and 48 h, and the block was complete after 72 h. The extent of the in vivo
      ADP ribosylation of the Gi/Go proteins, monitored at each time point by in vitro
      [32P]ADP-ribosylation and Western blotting, demonstrated a profound ADP
      ribosylation at 48 and 72 h. As detected by Western blotting, the rates of ADP
      ribosylation by PTX and the onset of decreased expression varied among the
      different G-proteins. G alpha o was virtually eliminated after only 24 h of PTX
      treatment. G alpha i2 was markedly affected by 48 h; G alpha i3 was little
      affected until 72 h.

PMID- 7720631
TI  - Marked changes of arginine vasopressin, oxytocin, and corticotropin-releasing
      hormone in hypophysial portal plasma after pituitary stalk damage in the rat.
AB  - Mechanical compression of the pituitary stalk with the help of a blunt
      stereotaxic knife results in posterior pituitary denervation (PPD) and sprouting
      proximal to the injury, leading to formation of an ectopic neurohypophysis in the
      stalk. This provides an experimental model for those cases in which traumatic
      damage severs the nerve fibers to the neural lobe but does not obliterate the
      hypophysial-portal circulation. The effect of PPD on the hypophysial-portal
      concentration profile of putative ACTH secretagogues as well as basal and
      stimulated ACTH secretion in vitro were investigated at varying times after PPD.
      The contents of arginine vasopressin (AVP) and oxytocin (OT) in extracts of the
      stalk median eminence 1 week after PPD were markedly elevated, whereas
      corticotropin-releasing hormone (CRH) content was unaffected. Levels of these
      three neuropeptides in hypophysial-portal blood collected under anesthesia from
      the proximal stump of the transected stalk (or the ectopic neural lobe) were
      measured at weekly intervals in groups of rats after sham or PPD surgery.
      Hypophysial-portal AVP levels showed a monotonic increase with time after PPD
      from a 1.8-fold elevation at 1 week post-PPD to a maximum concentration 6-fold
      greater than that in sham groups at 4 weeks post-PPD. Portal plasma OT levels
      also exhibited extreme elevation. In contrast, portal plasma CRH levels showed an
      initial 72% decline 1 week post-PPD. We suggest that mechanical damage to the
      pituitary stalk and the subsequent sprouting redirected secretion of AVP and OT
      from the neural lobe to the pituitary stalk. This caused sustained elevations of
      portal plasma concentrations of AVP and OT. The resulting tonic exposure to AVP
      and/or OT may down-regulate anterior pituitary receptors to these
      neurohypophyseal peptides and indirectly decrease CRH release into the portal
      circulation.

PMID- 7720632
TI  - Progesterone receptor messenger ribonucleic acid in the primate corpus luteum
      during the menstrual cycle: possible regulation by progesterone.
AB  - In classical target tissues, progesterone (P) down-regulates its own receptor,
      yet in the primate corpus luteum, progesterone receptors (PRs) exist within a
      very high local P milieu. The percentage of luteal cells staining PR-positive by
      immunocytochemistry is highest at the midluteal phase of the menstrual cycle
      during the period of peak serum P. To investigate the regulation of luteal PRs,
      we developed a solution hybridization/ribonuclease protection assay for the
      analysis of PR messenger RNA (mRNA) in macaque corpora lutea (n = 3-4/group). A
      332-basepair fragment of the macaque PR complementary DNA corresponding to the
      hormone-binding region was used as a template for riboprobe production; the
      specific hybridization of this riboprobe with PR mRNA was confirmed with Northern
      analysis. P regulation of luteal PR mRNA was investigated by administering
      trilostane, a 3 beta-hydroxysteroid dehydrogenase inhibitor, to female rhesus
      macaques beginning on day 6 or 7 of the luteal phase, which reduced serum P until
      the time of lutectomy. By 18 h after trilostane treatment, luteal PR mRNA levels
      were significantly elevated compared to untreated control values (mean +/- SEM,
      2.0 +/- 0.4 vs. 0.7 +/- 0.3; P < 0.05). Reduction in P levels for 4 days after
      trilostane administration decreased luteal PR mRNA levels compared with control
      values (0.50 +/- 0.02 vs. 1.1 +/- 0.2; P < 0.05). To characterize changes in PR
      mRNA during the lifespan of the corpus luteum, mRNA levels in luteal tissues from
      the early, mid-, mid-late, and late luteal phases were determined. PR mRNA levels
      were lowest during the early luteal phase and increased (P < 0.05) 3-fold by the
      mid-late luteal phase; this higher PR mRNA level was maintained throughout the
      remainder of the luteal phase. These data indicate that P or a metabolite may
      acutely regulate primate luteal PR mRNA in a manner consistent with PR regulation
      in classical P target tissues. In contrast, PR mRNA levels parallel increases in
      P and PR-positive luteal cells during the early, mid-, and mid-late portions of
      the luteal phase. High PR mRNA levels are maintained during luteal regression as
      P and the percentage of PR-positive cells decline, suggesting that PR and PR mRNA
      are regulated in an asynchronous manner during the lifespan of the corpus luteum
      in the menstrual cycle.

PMID- 7720633
TI  - Impairment of the modulation by glucose of hepatic gluconeogenesis in the
      genetically obese (fa/fa) Zucker rat.
AB  - Genetically obese (fa/fa) Zucker rats show oral glucose intolerance, an
      alteration that has been attributed at least in part to an impaired suppression
      of hepatic glucose output after the ingestion of glucose. In this work, we
      studied the influence of different concentrations of glucose (2.5-30 mM) on
      gluconeogenesis from a mixture of [14C]lactate-pyruvate as well as on fructose
      2,6-bisphosphate levels, pyruvate kinase activity, and flux through the reaction
      catalyzed by 6-phosphofructo-1-kinase, in hepatocytes isolated from fed obese
      (fa/fa) or lean (Fa/-) rats. In hepatocytes isolated from lean rats, incubation
      with increasing concentrations of glucose caused a dose-dependent inhibition of
      gluconeogenesis (5.02 +/- 0.54 and 1.82 +/- 0.33 mumol lactate converted to
      glucose/g cells.20 min in hepatocytes incubated in the presence of 2.5 and 30 mM
      glucose, respectively; n = 4 experiments; P < 0.01) together with a significant
      elevation of the fructose 2,6-bisphosphate content and a stimulation of the flux
      through 6-phosphofructo-1-kinase reaction. Glucose also provoked a dose-dependent
      activation of pyruvate kinase in the absence of changes in the cellular
      concentration of cAMP. In liver cells from obese animals, gluconeogenesis was not
      significantly modified by raising the glucose concentration in the incubation
      medium (1.26 +/- 0.11 and 0.83 +/- 0.14 mumol lactate converted to glucose/g
      cells.20 min in hepatocytes incubated with 2.5 and 30 mM glucose, respectively; n
      = 4 experiments; P = 0.11) despite significant increases in both fructose 2,6
      bisphosphate levels and flux through the 6-phosphofructo-1-kinase reaction. In
      these cells, pyruvate kinase was only slightly activated by high glucose
      concentrations. These results indicate that, unlike fructose 2,6-bisphosphate
      levels and flux through the 6-phosphofructo-1-kinase reaction, hepatic
      gluconeogenesis is unresponsive to high glucose concentrations in genetically
      obese (fa/fa) rats.

PMID- 7720634
TI  - Transcriptional activation of the follicle-stimulating hormone beta-subunit gene
      by activin.
AB  - Activin markedly stimulates FSH beta messenger RNA (mRNA) levels in rat pituitary
      cells. Nonetheless, the molecular mechanisms through which activin enhances FSH
      beta gene expression are not clear. To assess the role of transcriptional
      activation in activin stimulation, we first transfected two -2300FSH beta Luc
      constructs into primary pituitary cells and treated them with activin in plated
      culture and perifusion. Basal expression of the constructs was low, and no
      activin response was observed. These results suggested that additional FSH beta
      sequences are required for basal expression or that the effects of activin are
      not transcriptional. An alternative approach for measuring transcriptional
      responses was developed based upon changes in the levels of FSH beta primary
      transcripts (FSH beta-PT; newly transcribed mRNAs that still contain the first
      intron) after activin (3 ng/ml) stimulation of perifused rat pituitary cells. An
      increase in FSH beta-PT was observed after 30 min of activin stimulation,
      preceding the first observable rise in mature FSH beta mRNA. Levels of FSH beta
      PT peaked between 1-2 h, then fell to a lower level (28% of maximal) at 4 h,
      which was maintained through 10 h of activin stimulation (36% of maximal at 10
      h). Mature FSH beta mRNA levels peaked between 2-4 h, which is after the increase
      in FSH beta-PT, and fell more gradually between 4-10 h of stimulation (56% of
      maximal at 10 h). Unstimulated levels of mature mRNA and FSH beta-PT did not vary
      significantly over the course of the experiments. Cotreatment with the
      transcriptional inhibitor actinomycin-D (2 microM) blocked activin stimulation of
      both FSH beta-PT and FSH beta mRNA, confirming the transcriptional basis for
      these events. In summary, we have documented rapid and sequential increases in
      FSH beta-PT and mature FSH beta mRNAs after activin stimulation, which are
      prevented by transcriptional blockade. These data provide evidence that the
      increase in FSH beta mRNA levels after activin treatment are at least partly due
      to transcriptional activation of the FSH beta gene.

PMID- 7720635
TI  - Monoclonal antibodies specific for rat relaxin. VIII. Passive immunization with
      monoclonal antibodies throughout the second half of pregnancy reduces water
      consumption in rats.
AB  - Recent studies demonstrated that exogenous relaxin promoted drinking in
      nonpregnant rats. The purpose of this investigation was to determine the
      influence of endogenous relaxin on water consumption in pregnant rats. To that
      end, a monoclonal antibody specific for rat relaxin, designated MCA1, was used to
      passively neutralize endogenous relaxin throughout the second half of pregnancy
      in intact rats. Five milligrams of highly purified MCA1 were administrated iv to
      rats daily from days 12-22 of pregnancy. Controls received either a monoclonal
      antibody for fluorescein (monoclonal antibody control) or PBS (vehicle control).
      The amount of water consumed and both the total duration of water consumption and
      the total number of episodes when water was consumed were determined daily during
      both dark and light periods for all treatment groups. From days 13-22 of
      pregnancy, all three of these parameters of water consumption increased during
      the 10-h dark period (P < 0.01), but not during the 14-h light period. The mean
      daily water consumption in MCA1-treated rats was significantly less than that in
      controls (P < 0.05). Relaxin's effects on water consumption were limited to the
      14-h light period (P < 0.01). No difference was found in daily water consumption
      between the MCA1-treated and control groups during the 10-h dark period. There
      was a tendency during the light period for both the total duration of water
      consumption (P = 0.06) and the total number of episodes when water was consumed
      (P = 0.13) to be less in MCA1-treated rats than in controls. Food consumption and
      body weight increased as pregnancy progressed, but no differences were found
      among the three treatment groups. We conclude that endogenous relaxin has effects
      on water consumption. It promotes water consumption during the daily light period
      in the second half of pregnancy in rats. Thus, relaxin may be a dipsogenic agent.

PMID- 7720636
TI  - Androgen ablation-induced programmed death of prostatic glandular cells does not
      involve recruitment into a defective cell cycle or p53 induction.
AB  - Proliferating cells characteristically undergo programmed (i.e. apoptotic) death
      if their progression through the cell cycle is sufficiently perturbed. To
      determine whether androgen ablation-induced programmed death of prostatic
      glandular cells involves apoptosis triggered by recruitment of nonproliferating
      cells into a perturbed cell cycle, rat ventral prostates were assessed temporally
      after castration for several stereotypical molecular stigmata of entry into the
      proliferative cell cycle. Northern blot analysis was used to assess levels of
      transcripts from genes characteristically activated 1) during the transition from
      quiescence (G(0)) into G1 of the proliferative cell cycle (cyclin-D1 and cyclin
      C), 2) during the transition from G1 to S (cyclin-E, cdk2, thymidine kinase, and
      H4-histone), and 3) during progression through S (cyclin-A). Although levels of
      each of these transcripts increased as expected in prostatic glandular epithelial
      cells stimulated to proliferate by the administration of exogenous androgen to
      previously castrated rats, levels of the same transcripts decreased in prostatic
      glandular cells induced to undergo apoptosis after androgen withdrawal. Northern
      and Western blot analyses also demonstrated that there was no increase in
      prostatic p53 messenger RNA or protein content per cell after androgen ablation.
      Likewise, after castration, there was no enhanced prostatic expression of the
      WAF1/CIP1 gene, a gene whose expression is known to be induced in both a p53
      dependent and -independent manner during recruitment from G0 into G1. In
      addition, androgen ablation-induced apoptosis of prostatic glandular cells was
      not accompanied by retinoblastoma protein phosphorylation, which is
      characteristic of progression into late G1. Nuclear run-on assays demonstrated
      that there was no increase in the prostatic rate of transcription of the c-myc
      and c-fos genes after castration. These results demonstrate that prostatic
      glandular cells undergo programmed death in G(0) without recruitment into the G1
      phase of a defective cell cycle, and that an increase in p53 protein or its
      function is not involved in this death process.

PMID- 7720637
TI  - Long-term effects of nicotinamide-induced inhibition of poly(adenosine
      diphosphate-ribose) polymerase activity in rat pancreatic islets exposed to
      interleukin-1 beta.
AB  - Nicotinamide (NIC) is presently extensively studied as a potential agent that
      might prevent the development of insulin-dependent diabetes mellitus. This study
      aimed to examine the consequence of exposing isolated rat pancreatic islets to
      various concentrations of NIC (0, 0.5, 1.0, 5.0, 10, and 25 mM) over a prolonged
      period (6 days) in tissue culture and also to assess the efficacy of NIC to
      counteract interleukin-1 beta (IL-1; 25 U/ml)-induced beta-cell dysfunction.
      Except for a 30-40% increase at 5.0 mM NIC, the insulin content of islets was not
      affected by NIC. Also, the islet DNA content remained essentially unchanged. The
      insulin accumulation in the culture medium declined at 5-25 mM NIC between days 4
      6. The insulin release in response to 16.7 mM glucose on day 6 was enhanced after
      culture with the addition of 0.5 mM NIC, but 25 mM NIC caused a strong inhibition
      of insulin secretion. However, neither the (pro)insulin nor the total protein
      biosynthesis rate of the islets was affected by NIC. A significant inhibition of
      the islet poly(ADP-ribose) polymerase activity by 40-80% was observed at 5-25 mM
      NIC. IL-1 was then tested together with 1.0 and 10 mM NIC. The islet DNA content
      was markedly reduced in all groups treated with IL-1, as was the medium insulin
      accumulation. Moreover, NIC failed to prevent IL-1 induced impairment of islet
      insulin release on day 6. The cytokine induced a very pronounced and sustained
      increase in the medium nitrite accumulation, and NIC could not influence this
      elevation. Thus, these data show that prolonged exposure to elevated NIC levels
      impaired the function of rat beta-cells, and NIC failed to counteract IL-1
      actions. Whether these events are mimicked in the ongoing clinical trials with
      NIC remain to be established.

PMID- 7720638
TI  - Development and characterization of a simian virus 40-transformed, temperature
      sensitive rat antimesometrial decidual cell line.
AB  - The rat decidual tissue is formed by two cell populations, which express
      different genes and play diverse roles in pregnancy. Cells that decidualize in
      the antimesometrial region secrete several hormones and serve as a true endocrine
      gland. Isolation and maintenance of these decidual cells in primary culture is
      difficult. The goal of these experiments was to develop a cell line to serve as a
      model to study the expression and regulation of various genes specific to the
      antimesometrial decidual cells. Decidualization was induced in pseudopregnant
      rats. The antimesometrial decidua was dissected out, and cells were enzymatically
      dissociated and were cultured for 18 h at 37 C in RPMI-1640 medium containing 10%
      fetal bovine serum. Cells were washed repeatedly and then infected with a
      temperature-sensitive mutant of the simian virus. Transformed cells were
      maintained at the permissive temperature (33 C) until colonies were identified
      and harvested. Whereas primary cells in culture did not divide, the cloned
      decidual cell lines demonstrated transformed features; they multiplied at 33 C
      and formed multilayers. At the nonpermissive temperature (39 C), cell replication
      decreased, and after 4 days of culture the cells lost their transformed phenotype
      and continued to grow as a monolayer similar to primary cells. Cells under these
      conditions also assumed morphological characteristics similar to antimesometrial
      cells: polynucleated, large, and having cytoplasm filled with lipid droplets.
      Interestingly, cells cultured at 39 C that were shifted back to 33 C resumed
      rapid growth. To determine whether these cells also express messenger RNAs
      (mRNAs) found in normal antimesometrial decidual cells, the presence of activin
      beta A mRNA was investigated by Northern analysis and reverse transcription
      polymerase chain reaction. A single 6.8-kilobase activin beta A transcript was
      expressed abundantly at both 33 and 39 C, indicating that even when cells are
      rapidly dividing they express activin beta A. Activin beta B mRNA was also
      expressed in these cells, although in lower abundance, as were two binding
      proteins for activin, activin receptor II and follistatin. The activin beta A and
      beta B genes were responsive to cAMP stimulation in these cells. Since the
      hallmark of the antimesometrial decidual cells is the secretion of PRL-related
      hormones, the expression of decidual PRL-related protein and PRL-like protein B
      was examined. Northern analysis revealed a major 1.2-kilobase transcript of PRL
      like protein B expressed equally at both temperatures.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7720639
TI  - Regulation of Na+/H+ exchange in rat adipocytes; effects of insulin.
AB  - The activity of the Na+/H+ exchanger was examined by acidifying the intracellular
      pH (pHi) with Na+ propionate (NaP) and monitoring the recovery in the absence of
      HCO3- in rat adipocytes. Acidification of pHi, monitored with 2',7'-bis-(2
      carboxyethyl)-5(6)-carboxyfluorescein, decreased the resting pHi from 7.25 +/-
      0.01 to 6.70 +/- 0.01. A spontaneous pHi recovery to 6.90 +/- 0.02 was inhibited
      by 300 microM amiloride. This effect was Na+ specific, as recovery did not occur
      in cells exposed to K+ propionate (KP). The addition of NaCl (30 mM) to KP
      induced pHi alkalinization. Acidification of pHi increased 22Na+ transport from
      0.60 +/- 0.12 nmol/10(5) cells.min at resting pHi to 2.893 +/- 0.129 (P < 0.001)
      and 7.984 +/- 0.312 (P < 0.001) in the first and tenth minutes, respectively.
      Amiloride inhibited this 5- and 14-fold stimulation by 85% (P < 0.001). Insulin
      in the presence of 100 microM ouabain stimulated Na+ influx by more than 15% (P <
      0.01). Ethylisopropylamiloride (10 microM) inhibited the effect of insulin by 85%
      (P < 0.001). Intracellular Na+, measured with a Na(+)-specific electrode,
      increased by 10-fold in acid-loaded cells compared to that in Na(+)-depleted
      cells (10.750 +/- 0.479 vs. 1.045 +/- 0.100 mM; P < 0.001). Amiloride decreased
      NaP-stimulated intracellular Na+ by 82% (P < 0.001). To our knowledge, this is
      the first report showing the presence of an insulin-responsive and amiloride
      sensitive Na+/H+ exchanger that regulates pHi by a Na(+)-specific and pHi
      dependent mechanism in rat adipocytes.

PMID- 7720640
TI  - Glucose-6-phosphatase activity in islets from ob/ob and lean mice and the effect
      of dexamethasone.
AB  - In previous studies we demonstrated a much greater rate of glucose cycling
      (glucose-->glucose-6-P-->glucose) in islets from ob/ob mice than from lean litter
      mates. Cycling was further augmented by dexamethasone treatment. To determine
      whether these findings could be accounted for by increased islet glucose-6
      phosphatase activity, we have now measured that enzyme's activity in
      permeabilized and sonicated islets and in islet microsomes. Activity in
      permeabilized islets from ob/ob mice was 19 times more than from lean litter
      mates (17.7 +/- 2.9 vs. 0.9 +/- 0.2 pmol/islet/min). Activity was 6 times higher
      when calculated per microgram of protein or microgram of DNA. Treatment of ob/ob
      mice with dexamethasone (25 micrograms/daily for 3 days) increased activity 2- to
      3-fold. Activities were about twice as much in sonicated as permeabilized islets.
      There was no difference between glucose-6-phosphatase activity in microsomes
      prepared from islets of ob/ob and from lean mice, and the activity was relatively
      low. Thus, permeabilized islets can be used to determine glucose-6-phosphatase
      activity and study its regulation. The higher glucose cycling in islets of ob/ob
      mice and its stimulation by dexamethasone can be attributed to increased glucose
      6-phosphatase activity.

PMID- 7720641
TI  - An alternatively spliced human insulin-like growth factor-I transcript with
      hepatic tissue expression that diverts away from the mitogenic IBE1 peptide.
AB  - An alternatively spliced transcript of the human insulin-like growth factor-I
      (IGF-I) gene is described. The transcript was identified in human liver RNA by
      reverse transcriptase-polymerase chain reaction, cloning, and sequencing. It
      contained IGF-I exons 3 and 4, 49 basepairs of exon 5, then exon 6 (exon 4-5-6).
      The 5'-donor site at the exon 5-6 junction was a cryptic 5'-donor splice site
      (IGF633). The 3'-acceptor site of the splice was the usual intron-exon 6
      junction. A second pair of primers across the exon 5-exon 6 junction was used to
      confirm the presence of the transcript by reverse transcriptase-polymerase chain
      reaction. Cloning and sequencing this second fragment confirmed the presence of
      this splice in human liver. The exon 4-5-6 transcript was quantified at about 10%
      relative to the exon 4-6 transcript in human livers (n = 7 subjects), but was not
      detected in other tissues. The exon 4-5-6 transcript was found in cultured human
      hepatoma HepG2 cells and increased, relative to exon 4-6 transcripts, in response
      to GH, but not in cultured human lymphoblast IM-9 cells. The exon 4-5-6 splice
      predicts a prepro-IGF-I of 158 amino acid residues, with an E-peptide sequence of
      24 residues (Ec). The deduced Ec peptide sequence is 73% homologous to the rat Eb
      peptide sequence. The predicted final residues of the Ec peptide are frameshifted
      exon 6 codons ending in an in-frame stop codon. The predicted peptide sequences
      of Ec and Eb differ at the cleavage site of the Eb-peptide fragment (IBE1), which
      has been shown to have mitogenic activity. These data suggest that 1) the exon 4
      5-6 splice has hepatic tissue expression and occurs by the use of a cryptic 5'
      donor consensus splice site (IGF633) in exon 5; 2) exon 4-5-6 can be hormonally
      regulated in cultured human HepG2 cells; 3) exon 4-5-6 is the human counterpart
      of the rat IGF-IEb, because the complementary DNA and predicted sequences are
      homologous; and 4) the production of IBE1 is potentially regulated by alternative
      splicing.

PMID- 7720642
TI  - Tumor-stroma interactions and stromal cell density regulate hepatocyte growth
      factor protein levels: a role for transforming growth factor-beta activation.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF), a fibroblast-derived mediator
      of epithelial and endothelial growth and motility, is regulated by factors
      present in media conditioned by breast tumor cell lines. Both inhibitory and
      stimulatory effects were observed dependent on culture conditions. The present
      work shows that breast tumor cell conditioned medium contains a latent HGF/SF
      inhibitory activity, which can be activated by a variety of treatments known to
      activate latent transforming growth factor-beta. Using blocking antibodies and
      other criteria, we show that transforming growth factor-beta present in
      epithelial cell conditioned medium is primarily responsible for mediating the
      down-regulation of fibroblast HGF/SF. Epithelial cell conditioned medium also
      contains a trypsin-sensitive and heat-stable stimulatory activity. Stromal cell
      density but not proliferation rate markedly alters HGF/SF expression. These
      results indicate that the expression of at least one epithelial morphogen,
      HGF/SF, is interdependently regulated by mesenchymal condensation and by factors
      released by neighboring epithelial and carcinoma cells.

PMID- 7720643
TI  - Simvastatin inhibits the cellular signaling and proliferative action of arginine
      vasopressin in cultured rat glomerular mesangial cells.
AB  - The present study was undertaken to determine whether an inhibitor of 3-hydroxy-3
      methylglutaryl coenzyme A (HMG CoA) reductase, simvastatin, modulates the
      cellular action of arginine vasopressin (AVP) in the cultured rat glomerular
      mesangial cells. AVP increases cellular free calcium ([Ca2+]i) in a dose
      dependent manner. The 1 x 10(-7) M AVP-mobilized [Ca2+]i was significantly
      reduced in the cells pretreated with 1 x 10(-6) M simvastatin. AVP produced a
      biphasic change in cellular pH, namely, an early acidification followed by a
      sustained alkalinization, and the AVP-induced cellular alkalinization disappeared
      after exposing to simvastatin. 1 x 10(-7) M AVP activated mitogen-activated
      protein (MAP) kinase from 15.5-30.4 pmol/mg protein, an effect significantly less
      in the presence of simvastatin. Also, 1 x 10(-7) M AVP significantly increased
      [3H]thymidine incorporation by 1.6-fold, and its incorporation was totally
      diminished in cells pretreated with simvastatin. The AVP-induced [Ca2+]i
      mobilization and MAP kinase activation were totally restored when cells were
      preexposed to a mixture of mevalonate and simvastatin. [3H]AVP receptor binding
      was not affected by the simvastatin treatment. 1 x 10(-7) AVP increased inositol
      trisphosphate production by 1.8-fold, which was significantly reduced by the
      presence of simvastatin. These results may indicate that nonsterol pathway plays
      a crucial role in the cellular action of AVP to produce cell growth of glomerular
      mesangium.

PMID- 7720644
TI  - Characterization of 5'-heterogeneity of the rat GLUT4/muscle-adipose glucose
      transporter gene product.
AB  - To examine the mechanisms responsible for tissue-specific, nutritional, and
      metabolic regulation of the GLUT4/muscle-adipose specific glucose transporter, we
      isolated and characterized the properties of the rat GLUT4 gene. Examination of
      the sequenced 2.5-kilobase flanking DNA revealed substantial identity with that
      of the mouse and human GLUT4 genes, with the greatest degree of sequence identity
      within the proximal 1000 basepairs up-stream of the GLUT4 open reading frame.
      Primer extension analysis identified a unique single transcription initiation
      site 176 basepairs up-stream from the start of translation. However, ribonuclease
      mapping revealed the presence of a previously undescribed alternatively spliced
      form of GLUT4 messenger RNA. Approximately 75% of the GLUT4 transcripts consisted
      of a fully spliced messenger RNA, and 25% was expressed as an unspliced intron
      containing species. The ratios of 5' spliced and unspliced messages were
      invariant in adipose, cardiac, and skeletal muscle tissues. In vitro translation
      of reporter constructs containing both the spliced and unspliced leader
      demonstrated a functional difference between these two transcripts, with the
      unspliced form translated approximately 5-fold more than the fully spliced
      species. These data demonstrate the presence of 5'-heterogeneity of the GLUT4
      transcripts, which underlies differences in translational efficiency in vitro.

PMID- 7720645
TI  - Replacement with recombinant human inhibin immediately after orchidectomy in the
      hypophysiotropically clamped male rhesus monkey (Macaca mulatta) maintains
      follicle-stimulating hormone (FSH) secretion and FSH beta messenger ribonucleic
      acid levels at precastration values.
AB  - This study directly tested the inhibin hypothesis by examining the ability of
      replacement with recombinant human (rh-) inhibin, either alone or in combination
      with testosterone (T), to maintain FSH secretion and FSH beta messenger RNA
      (mRNA) at intact levels after orchidectomy in the hypophysiotropically clamped
      juvenile rhesus monkey. Thirteen male monkeys (11-21 months of age) received an
      intermittent i.v. infusion of GnRH (0.1 microgram/min for 3 min every 3 h). After
      4-6 weeks of GnRH stimulation, 10 animals were orchidectomized, and 3 monkeys
      were sham castrated. Hormone replacement was initiated at castration and
      maintained for 4 days. Three monkeys received a combination of inhibin and T
      replacement, 4 monkeys received replacement with inhibin alone, and 3 monkeys
      received T replacement alone. A continuous i.v. infusion of rh-inhibin (832
      ng/h.kg) was used to replace the testicular protein, whereas SILASTIC capsules
      were implanted sc for T replacement. The FSH response to castration and hormone
      replacement was determined by measuring circulating concentrations of this
      gonadotropin before a GnRH pulse and for 3 h thereafter on the day before surgery
      and on days 2 and 4 postcastration. Circulating immunoactive inhibin was measured
      by a RIA that recognizes the free alpha-subunit of inhibin as well as inhibin
      dimers. At the end of the study, anterior pituitaries were collected for analysis
      of steady state levels of FSH beta, LH beta, and alpha-subunit mRNAs. Steroid
      replacement alone, which produced circulating T concentrations in the upper
      physiological range, failed to prevent the postcastration increases in
      circulating FSH concentrations and pituitary FSH beta mRNA levels. In contrast,
      when circulating immunoactive inhibin in T-replaced monkeys was maintained at
      precastration levels (approximately 2 ng/ml) by infusion of rh-inhibin, FSH
      secretion and synthesis were held at control values. When T was omitted from
      combined replacement, the FSH-suppressing action of the recombinant hormone was
      not compromised. These results demonstrate that rh-inhibin is biologically active
      in the monkey, and the action of inhibin to suppress FSH synthesis and secretion
      does not require a concomitant action of T. Moreover, because the
      hypophysiotropic drive to the pituitary-testicular axis was clamped, the FSH
      suppressing action of rh-inhibin must be at the pituitary.

PMID- 7720646
TI  - Functional characterization of hybrid receptors composed of a truncated insulin
      receptor and wild type insulin-like growth factor 1 or insulin receptors.
AB  - To assess the characteristics of hybrid receptors composed of one kinase-inactive
      alpha beta-insulin half-receptor and one endogenous alpha beta-insulin-like
      growth factor 1 (IGF-1) or insulin half-receptor, a cell line expressing an
      insulin receptor truncated by 365 amino acids (HIR delta 978) was studied, which
      lacks most of the cytoplasmic beta-subunit. Analysis by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis under nonreducing conditions revealed four
      distinct receptor species: endogenous receptors, the more rapidly migrating HIR
      delta 978 homodimer, and two intermediate species representing HIR delta 978/IGF
      1 hybrid receptors and HIR delta 978/IR hybrid receptors. In vivo ligand-binding
      affinity of the hybrid receptors was studied by receptor-ligand cross-linking,
      and the delta 978/IGF-1R hybrid receptor was found to have a high affinity for
      IGF-1, whereas its affinity for insulin was low. Autophosphorylation studies of
      lectin-purified receptors revealed that neither the HIR delta 978 holoreceptor
      nor the hybrid receptors underwent autophosphorylation in response to either
      ligand, despite the presence of intact IGF-1 or insulin half-receptors in the
      hybrids. Neither hybrid receptor underwent ligand-induced endocytosis, as
      assessed with the bioactive photoaffinity probes B2(2-nitro-4-azidophenylacetyl)
      des-PheB1-insulin and N-epsilon B28-monoazidobenzoyl-IGF-1. In conclusion, the
      HIR delta 978/IGF-1R hybrid receptor has a high in vivo affinity for IGF-1 but
      not for insulin. Neither the delta 978/IGF-1R nor the delta 978/IR hybrids
      undergo autophosphorylation or ligand-induced endocytosis in response to either
      ligand, indicating that intramolecular trans-, rather than cis-, signal
      transduction is important in mediating autophosphorylation and endocytosis.

PMID- 7720647
TI  - Progesterone attenuation of alpha 1-adrenergic receptor stimulation of
      phosphoinositol hydrolysis in hypothalamus of estrogen-primed female rats.
AB  - These experiments examined whether the previously observed abolition by
      progesterone (P) of alpha 1-adrenergic potentiation of adenylyl cyclase activity
      in brain slices of estrogen-primed female rats is attributable to a reduced
      capacity of alpha 1-adrenoceptors to stimulate phosphoinositol hydrolysis. In
      preoptic area and hypothalamic slices from ovariectomized (OVX) female rats, both
      norepinephrine (NE) and the alpha 1-adrenergic agonist phenylephrine (PHE) were
      robust stimulators of inositol phosphate (IP) formation. The NE response was
      completely blocked by the alpha 1-adrenergic antagonist prazosin. PHE-induced IP
      formation in tissue from OVX females exposed for 48 h to estrogen alone was
      comparable to that in OVX controls. In hypothalamic tissue from OVX rats given
      estrogen plus P, NE and PHE activation of phosphoinositol hydrolysis was
      attenuated. Both chlorethylclonidine, an irreversible antagonist of alpha 1b
      adrenoceptors, and 5-methylurapidil, an alpha 1a-selective antagonist, reduced NE
      induced IP formation regardless of the hormonal condition of the animals.
      Analysis of PHE competition for [3H]prazosin binding indicated that agonist
      binding was of high affinity (Ki, 16-30 microM) and was unaffected by hormonal
      status. Therefore, P abolition of alpha 1-adrenergic augmentation of adenylyl
      cyclase is correlated with reduced phosphoinositol hydrolysis, but not with
      changes in alpha 1-adrenoceptor agonist binding affinity. Moreover, both alpha 1a
      and alpha 1b-adrenoceptors appear to work together to stimulate this second
      messenger system in the female rat hypothalamus.

PMID- 7720648
TI  - Expression of adenylyl cyclase subtypes in brown adipose tissue: neural
      regulation of type III.
AB  - Previous work has shown that neural stimulation of brown adipose tissue (BAT)
      increases norepinephrine-stimulated adenylyl cyclase (AC) activity 2- to 3-fold
      by a mechanism involving postreceptor alterations of the AC system. In view of
      the recent discovery of multiple AC subtypes, the purposes of this study were to
      determine which of these subtypes are present in BAT and to examine whether their
      expression is altered by neural stimulation. Direct hybridization and polymerase
      chain reaction analyses demonstrated that BAT expresses messenger RNAs (mRNAs)
      encoding AC-III, AC-IV, AC-V, and AC-VI subtypes. Of the subtypes detected in
      BAT, neural stimulation increased only AC-III mRNA levels. Activation of beta
      adrenergic receptors was sufficient to increase AC-III mRNA levels; however, the
      potency of beta-receptor agonists was greatly enhanced by simultaneous
      stimulation of alpha 1-adrenergic receptors. The close correlation between the
      increases in AC activity and the induction of AC-III mRNA across various
      physiological and pharmacological treatments indicates that this subtype is
      responsible for the increase in AC activity that occurs after adrenergic
      stimulation.

PMID- 7720649
TI  - Number and size of islets of Langerhans in pregnant, human growth hormone
      expressing transgenic, and pituitary dwarf mice: effect of lactogenic hormones.
AB  - To determine the effects of lactogenic hormones on pancreatic islet size and
      numbers, islets of 3-month-old female mice were intravitally stained by an ip
      injection of an alkaline-alcohol solution of diphenylthiocarbazone (dithizone;
      100 micrograms/g BW). After 15 min, animals were killed, and pancreases were
      removed, diced, cleared in glycerol, and whole mounted on slides. Major and minor
      axes of Zn dithizoate-stained islets were measured at x40 magnification. Islet
      areas and volumes were calculated. Animals and appropriate controls studied
      included 16-day pregnant, two lines of human GH-expressing transgenic, and two
      lines of pituitary PRL- and GH-deficient dwarf mice. Islet numbers per pancreas
      ranged from about 500-1200 in all groups except the transgenic mice, in which two
      of five animals in one group and one of five in the other showed significant
      increases in islet numbers (> 3 x SD control mean). In all cases, significant (P
      < 0.05) changes in both islet area and volume occurred. Area increased 2-fold in
      both pregnant and transgenic mice and decreased by a similar amount in dwarf
      mice. Islet volume increased 2- and 3-fold in pregnant and transgenic animals,
      respectively, and decreased 2- to 5-fold in dwarf mice. Analysis of the
      distributions of islet sizes revealed that almost all of the volume increases in
      the pregnant and transgenic mice and the decreases in dwarf mice were accounted
      for by alterations in the numbers and sizes of large (diameter, > 150 microns)
      islets. Our results with dwarf mice show that maintenance of islet numbers is not
      dependent upon pituitary PRL or GH; however, results with transgenic mice suggest
      that prolonged high levels of lactogens may induce islet neogenesis. The islet
      area and volume results for all of the mice studied support the hypothesis that
      lactogenic hormones are potent regulators of islet mass.

PMID- 7720650
TI  - Age-dependent changes in beta-adrenergic receptor subtypes and adenylyl cyclase
      activation in adipocytes from Fischer 344 rats.
AB  - Epididymal adipocytes were isolated from Fischer 344 rats aged 3, 6, 12, and 24
      months, to study the mechanisms responsible for age-dependent diminution in
      cellular adrenergic responsiveness. Messenger RNA (mRNA) levels for the beta 1-,
      beta 2-, and beta 3-adrenergic receptors (ARs) were compared across age groups
      and related to adenylyl cyclase activation by selective receptor agonists in
      adipocyte plasma membranes and activation of lipolysis in intact cells. mRNA
      levels for the beta 1-AR decreased by 60% between 3-6 months and remained at this
      reduced level through 12 and 24 months. A modest increase in beta 2-AR mRNA was
      noted between 3-12 months, but decreased between 12-24 months to levels seen in
      the 3-month-old group. mRNA for the beta 3-AR did not change between 3-6 months,
      but decreased by about 40% between 6-12 months, and by a further 50% between 12
      24 months. Lipolytic responsiveness also diminished with age, and regardless of
      whether beta 3-selective or beta 1/beta 2-selective agonists were used, the
      maximal release of glycerol was most severely blunted in adipocytes from 24-month
      old rats. The age-dependent changes in adenylyl cyclase activation by beta
      adrenergic agonists mirrored the observed changes in lipolytic responsiveness
      with respect to diminished efficacy. These results together with the similar
      forskolin-stimulated adenylyl cyclase activity among the groups suggest age
      dependent changes in activation of adenylyl cyclase at a prior step. This
      suggestion is also supported by the comparable inhibitory capacities of the alpha
      2-adrenergic and A1-adenosine signaling systems among the age groups. In view of
      the similar levels of Gs alpha, the age-dependent decrease in adrenergic
      responsiveness in rat adipocytes appears to result primarily from specific
      decreases in the expression of both beta 3-AR and beta 1-ARs.

PMID- 7720651
TI  - Kaliuretic peptide: the most potent inhibitor of Na(+)-K+ ATPase of the atrial
      natriuretic peptides.
AB  - The present investigation was designed to determine whether atrial natriuretic
      peptides consisting of amino acids 1-30 (i.e. long-acting natriuretic peptide),
      31-67 (vessel dilator), 79-98 (kaliuretic peptide), and 99-126 [atrial
      natriuretic factor (ANF)] of the 126 amino acid ANF prohormone inhibit sodium
      potassium-ATPase as part of their mechanism(s) of action for producing a
      natriuresis and/or kaliuresis. Kaliuretic peptide, long-acting natriuretic
      peptide, vessel dilator and ANF at their 10(-11) M concentrations inhibited Na(+)
      K(+)-ATPase 39.5%, 27.8%, 19.2%, and 4% respectively, in bovine renal medulla,
      whereas their inhibition in renal cortical membranes was 37.5%, 27.5%, 20%, and
      0%, respectively. Ouabain (0.5 mM) inhibited kidney medullary Na(+)-K(+)-ATPase
      45% and in the cortex, 38%. There was no additive effect of any of these peptides
      with ouabain suggesting that they are interacting with the same site on the Na(+)
      K(+)-ATPase as ouabain. To help elucidate the mechanism of these peptides'
      interaction with Na(+)-K(+)-ATPase, naproxen (0.5 mM), an inhibitor of
      prostaglandin synthesis, and direct measurement of prostaglandin E2 by RIA were
      used. Naproxen completely blocked the inhibition of Na(+)-K(+)-ATPase by
      kaliuretic peptide, long-acting natriuretic peptide, and vessel dilator
      suggesting that their inhibition of Na(+)-K(+)-ATPase in both the kidney medulla
      and cortex are mediated by prostaglandins. Direct measurement of prostaglandin E2
      revealed that kaliuretic peptide > long-acting natriuretic peptide > vessel
      dilator increased prostaglandin E2 synthesis, whereas ANF did not have any
      effect. Of interest, angiotensin II and ouabain inhibition of Na(+)-K(+)-ATPase
      were also completely blocked by naproxen.

PMID- 7720652
TI  - Cyclic adenosine 3',5'-monophosphate stimulation of placental proliferin and
      proliferin-related protein secretion.
AB  - To identify factors that regulate proliferin (PLF) and PLF-related protein (PRP)
      secretion by the mouse placenta, placental cells from day 9 of pregnancy were
      cultured for up to 5 days, and PLF and PRP release into the medium was assessed
      by RIA. Transforming growth factor-alpha, interleukin-1 alpha, and interleukin-6
      did not regulate either PLF or PRP secretion. However, treatment of primary
      placental cell cultures with 8-bromo-cAMP, cholera toxin, or forskolin resulted
      in 2- to 3-fold increases in the percentages of PLF- and PRP-producing cells in
      the population and corresponding increases in both PLF and PRP messenger RNA and
      secreted protein. The increase in the number of PLF-producing cells was
      accompanied by an increase in the number of cells expressing both PLF and mouse
      placental lactogen-I. These data suggest that cAMP levels can regulate
      trophoblast giant cell differentiation and, consequently, the amount of PLF and
      PRP secretion.

PMID- 7720653
TI  - Alternative splicing of a 48-nucleotide exon generates two isoforms of the human
      calcitonin receptor.
AB  - A portion of the human calcitonin receptor (hCTR) gene corresponding to the
      region of the porcine gene at which alternative splicing generates two CTR
      isoforms was isolated by polymerase chain reaction amplification of placental
      DNA. In contrast to the porcine CTR gene, in which two acceptor sites in exon 8
      are separated by 48 nucleotides, we found a distinct 48-nucleotide exon in the
      hCTR gene that is present approximately 6400 basepairs from the up-stream exon,
      which corresponds to porcine exon 7, and approximately 1100 basepairs from the
      down-stream exon, which corresponds to porcine exon 8. Splicing of this exon
      accounts for the two isoforms of hCTR, containing or not containing a 16-amino
      acid insertion in the first putative intracellular loop. A region similar to the
      intron 7-exon junction in the porcine CTR gene is present in the human gene, but
      contains four extra nucleotides that shift the reading frame. Using probes
      derived from these introns in somatic cell and in situ hybridization analyses, we
      assigned the CTR gene to human chromosome band 7q21.2-q21.3. Thus, human and
      porcine species have evolved distinct mechanisms to generate two similar CTR
      isoforms.

PMID- 7720654
TI  - Androgens rapidly increase the cytosolic calcium concentration in Sertoli cells.
AB  - We demonstrate that androgens rapidly and specifically increase intracellular
      calcium in Sertoli cells, investigate the mechanism, and suggest the unifying
      hypothesis that calcium might be a common intracellular molecular effector to
      explain the known synergism between FSH and testosterone (T) action on Sertoli
      cells in support of spermatogenesis. In freshly isolated Sertoli cells, T and its
      5 alpha-reduced metabolite dihydrotestosterone increased intracellular calcium
      from 83 +/- 4 to 147 +/- 8 and 167 +/- 29 nM, respectively, whereas estradiol had
      minor (117 +/- 9 nM) and progesterone no (80 +/- 6 nM) effect. The effect of T
      was rapid (20-40 sec) and inhibited by 1) preincubation with either a pure
      nonsteroidal antiandrogen (hydroxyflutamide) or a 5 alpha-reductase inhibitor
      (finasteride) or 2) removal of extracellular calcium (47 +/- 4 nM) or
      pharmacological blockade of voltage-activated (62 +/- 5 nM) or voltage
      independent (55 +/- 14 nM) membrane calcium channels. These findings suggest that
      the T-induced rise in Sertoli cell cytosolic calcium involves sequential 5 alpha
      reduction, binding to a classical androgen receptor, and activation of
      transmembrane influx of extracellular calcium. Immobilization of T by conjugation
      to a large carrier molecule (BSA) to prevent steroid entry into Sertoli cells
      also resulted in a rapid increase in cytosolic calcium to a similar magnitude as
      unconjugated T, consistent with a plasma membrane site of action. This finding
      together with the rapid cytosolic calcium rise caused by T argues for the
      possible existence of a short term, nongenomic effects in hormonal regulation of
      Sertoli cell function in addition to the well known, slower genomic response.

PMID- 7720655
TI  - Gonadotropin-dependent and gonadotropin-independent development of inhibin
      subunit messenger ribonucleic acid levels in the mouse ovary.
AB  - The inhibins and activins are dimeric growth factors with important regulatory
      functions during development. In this study, changes in inhibin subunit messenger
      RNA (mRNA) levels were measured in the ovary during early postnatal development
      in the normal mouse and the hypogonadal (hpg) mouse, which lacks circulating
      gonadotropins. Levels of inhibin alpha-, beta A-, and beta B-subunit mRNAs were
      measured relative to beta-actin using a semiquantitative reverse transcription
      polymerase chain reaction technique. Transcripts encoding all three subunits were
      present at birth; the alpha-subunit was the most abundant, followed by beta A
      subunit (6% of alpha) and beta B-subunit (0.4% of alpha). After birth, levels of
      all three subunit transcripts increased between 6- and 10-fold. Changes in
      inhibin beta A- and beta B-subunit levels were most marked around 7 days, the
      period of secondary follicle development, whereas alpha-subunit transcript levels
      increased constantly after day 1 to reach a peak at 10 days, when mature
      secondary follicles are present. In hpg mice, levels of ovarian inhibin alpha
      subunit mRNA levels were normal at all ages up to 15 days. In contrast, inhibin
      beta A-subunit mRNA levels were normal at birth in hpg mice, but did not increase
      after that up to day 15. Levels of beta B-subunit mRNA were significantly lower
      than normal on day 1 in hpg mice and also failed to show a significant increase
      up to 15 days. These results show that inhibin subunit mRNA levels are
      differentially regulated during ovarian development in the mouse. Normal
      expression of beta-subunits is completely gonadotropin dependent around the
      period of late primary to secondary follicle development. The inhibin alpha
      subunit, in contrast, is expressed at a high level during development independent
      of gonadotropin stimulation.

PMID- 7720656
TI  - Transcriptional regulation of glial fibrillary acidic protein by corticosterone
      in rat astrocytes in vitro is influenced by the duration of time in culture and
      by astrocyte-neuron interactions.
AB  - In the rat hippocampus and cortex, the transcription of glial fibrillary acidic
      protein (GFAP), an astrocyte intermediate filament protein, is inhibited by
      glucocorticoids. The present study examined the regulation of GFAP expression by
      glucocorticoids in astrocytes in vitro. Corticosterone (CORT) increased GFAP
      messenger RNA, protein, and transcription rates in cultured primary neonatal
      astrocytes, responses opposite the GFAP responses to CORT in vivo. The direction
      of GFAP regulation by corticosterone in vitro is reversed by coculture with
      neurons or by extended culture for 3 months. The switch in the direction of GFAP
      regulation by CORT during prolonged culture is associated with a 3-fold increased
      prevalence of type II glucocorticoid receptor (GR). These findings were
      corroborated with a promoter construct that contained 1.9 kilobases of 5'-up
      stream rat GFAP DNA with a luciferase reporter. Thus, the direction of GFAP
      transcription to CORT is subject to the postreplicative time in culture and to
      interactions with neurons, in which 5'-up-stream sequences contain sufficient
      information to mediate the switch in the direction of the response to CORT. This
      in vitro model may be used to analyze how interactions of astrocytes with neurons
      or other cell types influence the hormonal regulation of GFAP.

PMID- 7720657
TI  - Early detection of secretogranin-II (SgII) in the human fetal pituitary:
      immunocytochemical study using an antiserum raised against a human recombinant
      SgII.
AB  - Secretogranin-II (SgII) is a protein contained within secretory granules of
      mainly gonadotrophs. The purpose of this study was to determine whether SgII
      immunoreactivity (SgII-IR) in the human fetal pituitary was temporally related to
      gonadotropin immunoreactivity. A specific antihuman SgII antiserum was thus
      required. A complementary DNA clone with an open reading frame for human (h) SgII
      was synthesized by reverse transcription-polymerase chain reaction from pituitary
      total RNA. This clone was used to obtain the SgII polypeptide (-9 to 152) as a
      fusion protein, in a heterologous expression prokaryotic system. Antisera against
      the fusion protein were raised in rabbits and checked for specificity and
      sensitivity through Western blotting. Human fetal pituitaries from week 6 of
      gestation onward were used for immunocytochemical studies. Consecutive semithin
      sections were treated with the specific antisera against hSgII, beta-endorphin,
      and hPRL and with monoclonal antibodies to hCG alpha, hLH, and hFSH. SgII
      immunoreactivity appeared at week 8 and was restricted to pituitary cells
      expressing beta-endorphin (100% colocalization). At week 9, FSH-positive cells
      did not contain SgII. From week 10, gonadotrophs progressively exhibited SgII-IR,
      up to 50% of that in FSH-containing cells at week 26. The granin was never found
      in PRL cells whatever the stage of development. The present data demonstrate that
      SgII-IR is detected very early in fetal life; however, the positive cells are not
      gonadotrophs, but corticotrophs. Within gonadotrophs, SgII appears subsequent to
      hormones. At birth, more than 90% of SgII-IR cells are represented by
      corticotrophs and gonadotrophs.

PMID- 7720658
TI  - Differential expression of pituitary adenylate cyclase-activating
      polypeptide/vasoactive intestinal polypeptide receptor subtypes in clonal
      pituitary somatotrophs and gonadotrophs.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal polypeptide (VIP) are hypothalamic factors believed to play a role in
      the regulation of anterior pituitary cell function. However, little is known
      about the expression of PACAP/VIP receptor (PVR) subtypes in such cells. Three
      PVR subtypes have recently been cloned: the PACAP-selective PVR1, and PVR2 and
      PVR3, which exhibit similar affinities for PACAP and VIP. In the present study we
      used the reverse transcription-polymerase chain reaction with PVR-specific
      primers to identify the PVR messenger RNAs (mRNAs) expressed in the somatotroph
      like GH4C1 and the gonadotroph-like alpha T3-1 cell lines. In parallel, the
      effects of PACAP and VIP on intracellular signaling were studied. GH4C1 cells
      were found to express mRNA only for the PVR3, and neither PVR1 nor PVR2 mRNA was
      found. PACAP and VIP stimulated Ca2+ influx responses in individual GH4C1 cells
      and were equipotent in stimulating cAMP production (EC50, 15 nM) in GH4C1 cell
      populations, but failed to stimulate inositol phospholipid (PI) turnover, results
      consistent with the expression of a PVR3. In contrast, alpha T3-1 cells expressed
      mRNA for PVR1 and PVR3, but not PVR2. The predominant splice variant forms of
      PVR1 observed were PVR1s and PVR1hop, although the other forms (PVR1hiphop and
      PVR1hip) were also seen at much lower levels. PACAP stimulated a Ca2+ store
      dependent Ca2+ spike and a sustained Ca2+ influx in individual alpha T3-1 cells,
      whereas VIP only stimulated Ca2+ influx. PACAP (EC50, 3 nM) was approximately
      1000-fold more potent than VIP (EC50, approximately 3 microM) in stimulating cAMP
      production. PACAP also stimulated PI turnover (EC50, approximately 20 nM),
      whereas VIP stimulated PI turnover only at very high (10 microM) concentrations.
      These results are indicative of the expression of a PVR1. Rat anterior pituitary
      tissue expressed mRNAs for PVR1, PVR3, and low levels of PVR2. The coexpression
      of different PVRs in the same cell type and the differential expression of PVRs
      in different cell types would allow for a complex regulation of anterior
      pituitary gland function by PACAP and VIP.

PMID- 7720659
TI  - The molecular response of bone to growth hormone during skeletal unloading:
      regional differences.
AB  - Hind limb elevation of the growing rat provides a good model for the skeletal
      changes that occur during space flight. In this model the bones of the forelimbs
      (normally loaded) are used as an internal control for the changes that occur in
      the unloaded bones of the hind limbs. Previous studies have shown that skeletal
      unloading of the hind limbs results in a transient reduction of bone formation in
      the tibia and femur, with no change in the humerus. This fall in bone formation
      is accompanied by a fall in serum osteocalcin (bone Gla protein, BGP) and bone
      BGP messenger RNA (mRNA) levels, but a rise in bone insulin-like growth factor-I
      (IGF-I) protein and mRNA levels and resistance to the skeletal growth-promoting
      actions of IGF-I. To determine whether skeletal unloading also induced resistance
      to GH, we evaluated the response of the femur and humerus of sham and
      hypophysectomized rats, control and hind limb elevated, to GH (two doses),
      measuring mRNA levels of IGF-I, BGP, rat bone alkaline phosphatase (RAP), and
      alpha 1(1)-procollagen (coll). Hypophysectomy (HPX) decreased the mRNA levels of
      IGF-I, BGP, and coll in the femur, but was either less effective or had the
      opposite effect in the humerus. GH at the higher dose (500 micrograms/day)
      restored these mRNA levels to or above the sham control values in the femur, but
      generally had little or no effect on the humerus. RAP mRNA levels were increased
      by HPX, especially in the femur. The lower dose of GH (50 micrograms/day)
      inhibited this rise in RAP, whereas the higher dose raised the mRNA levels and
      resulted in the appearance of additional transcripts not seen in controls. As for
      the other mRNAs, RAP mRNA in the humerus was less affected by HPX or GH than that
      in the femur. Hind limb elevation led to an increase in IGF-I, coll, and RAP
      mRNAs and a reduction in BGP mRNA in the femur and either had no effect or
      potentiated the response of these mRNAs to GH. We conclude that GH stimulates a
      number of markers of bone formation by raising their mRNA levels, and that
      skeletal unloading does not block this response, but the response varies
      substantially from bone to bone.

PMID- 7720660
TI  - Estrogen induces epidermal growth factor (EGF) receptor and its ligands in human
      fallopian tube: involvement of EGF but not transforming growth factor-alpha in
      estrogen-induced tubal cell growth in vitro.
AB  - We studied the estrogen-dependent expression of epidermal growth factor (EGF),
      transforming growth factor (TGF) alpha, and EGF receptor gene transcripts in
      human fallopian tubes in vivo and in vitro. Competitive polymerase chain reaction
      (PCR) was performed on the fallopian tube RNA samples from the postmenopausal
      women with or without estrogen replacement. Amounts of EGF, TGF alpha, and EGF
      receptors gene transcripts in the estrogen-treated group (n = 3) were
      significantly (P < 0.01) more than those in the untreated group (n = 3).
      Competitive PCR also showed that EGF, TGF alpha, and EGF receptor gene
      transcripts level in tubal cells were increased by estrogen in vitro: messenger
      RNA levels of these factors were significantly (P < 0.01, n = 3) increased in
      cells incubated with 10(-8) M estrogen compared with those in cells without
      estrogen treatment. We studied whether EGF and/or TGF alpha is involved in the
      estrogen-induced tubal cell growth in vitro. Estrogen enhanced the [3H]-thymidine
      incorporation into the cell in dose- and time-dependent manners in culture:
      estrogen treatment for more than 12 h significantly (P < 0.05) enhanced the [3H]
      thymidine incorporation into the cell at 10(-8) M. The estrogen-induced cell
      growth was observed in association with the increase in EGF, TGF alpha, and EGF
      receptor messenger RNA levels by estrogen. If the EGF and/or TGF alpha is
      involved in the cell growth, then the estrogen-induced cell growth should be
      suppressed by blocking the action of EGF and/or TGF alpha. Therefore, we examined
      the effects of neutralizing monoclonal antibodies against EGF, TGF alpha, and EGF
      receptors. Anti-EGF antibody significantly reduced the estrogen-induced increase
      in [3H]-thymidine incorporation, whereas anti-TGF alpha antibody failed to show
      the effect. Anti-EGF receptor antibody showed a significant suppressive effect on
      the estrogen-induced increase in [3H]-thymidine incorporation. Moreover, the
      growth inhibitory effect by 1 microgram/ml anti-EGF was restored by 10(-8) M EGF
      but not by TGF alpha even at 10(-6) M. All these data suggest that estrogen
      induces EGF and TGF alpha/EGF receptors in the human fallopian tube and that EGF
      but not TGF alpha may be involved in the estrogen-induced human tubal cell growth
      in vitro.

PMID- 7720661
TI  - Cell-type specific interactions between retinoic acid and thyroid hormone in the
      regulation of expression of the gene encoding ornithine aminotransferase.
AB  - The purposes of this study were to determine whether expression of the gene
      encoding ornithine aminotransferase (OAT) in the rat liver and kidney is
      regulated by retinoic acid (RA) and to characterize further the role of thyroid
      hormone in regulating the expression of this gene. The level of OAT messenger RNA
      (mRNA) was reduced 70% in the liver of animals fed a vitamin A-deficient diet
      relative to that in animals fed a vitamin A-sufficient diet. RA, administered at
      a dose of 20 micrograms/rat to A-deficient rats for 1 or 3 days, restored OAT
      mRNA to near the level observed in animals fed the A-sufficient diet. Retinol was
      also effective in this regard. T3, when injected alone at a dose of 10
      micrograms/100 g BW, had no effect on the level of OAT mRNA in the liver.
      However, when injected concurrently with RA, T3 blocked the ability of RA to
      induce OAT mRNA in the liver of rats fed the vitamin A-deficient diet. Animals
      made both vitamin A deficient and hypothyroid responded to RA in a manner similar
      to vitamin A-deficient animals. The vitamin A-deficient, hypothyroid rats
      responded somewhat differently to T3, however. T3 was unable to block the
      induction of OAT mRNA in the liver of vitamin A-deficient, hypothyroid rats when
      injected concurrently with RA for 1 day, but did block the induction of OAT mRNA
      by RA when these two hormones were injected concurrently for 3 days. These data
      indicate that RA and T3 exert opposing effects on the level of OAT mRNA in the
      liver. The effects of RA and T3 on OAT mRNA were markedly different in the
      kidney. Neither vitamin A deficiency nor RA had any apparent affect on the level
      of OAT mRNA in the kidney. T3, however, increased the level of OAT mRNA in the
      kidney of vitamin A-deficient rats. In the kidney of vitamin A-deficient,
      hypothyroid rats, T3 was unable to increase OAT mRNA when injected for 1 day, but
      did increase this mRNA when injected for 3 days. Together, these data indicate
      cell-type specific effects of both RA and T3 on the OAT gene.

PMID- 7720662
TI  - An abundant and specific binding site for the novel vasodilator adrenomedullin in
      the rat.
AB  - Rat adrenomedullin is a novel 50-amino acid peptide with structural similarities
      to the calcitonin family of peptides, calcitonin, calcitonin gene-related peptide
      (CGRP), and islet amyloid polypeptide (IAPP). Using rat [125I]adrenomedullin,
      specific binding sites were demonstrated in heart, lung, spleen, liver, soleus,
      diaphragm, gastrocnemius, and spinal cord membranes. The highest binding was
      present in heart and lung, which was further characterized. These sites exhibited
      saturation, dissociation, and competition. In rat lung, only rat (IC50 = 5.8 nM)
      and human (IC50 = 94 nM) adrenomedullin competed with [125I]adrenomedullin.
      However, in rat heart, rat (IC50 = 0.2 nM) and human (IC50 = 4.2 nM)
      adrenomedullin, IAPP (IC50 = 240 nM), and CGRP (IC50 = 1050 nM) all competed with
      [125I] adrenomedullin. Saturation analysis revealed binding capacities and
      dissociation constants of 2.8 +/- 0.3 pmol/mg protein and 1.3 +/- 0.3 nM,
      respectively, in lung and 0.47 +/- 0.11 pmol/mg protein and 0.41 +/- 0.14 nM in
      heart. Comparison with [125I]CGRP- and [125I]IAPP-binding sites in lung showed
      that rat adrenomedullin could potently inhibit at these sites (IC50 = 5 and 6 nM,
      respectively). Chemical cross-linking demonstrated a major band of 83,000 mol wt
      in lung, diaphragm, spleen, and liver and a band of 94,000 mol wt in heart,
      soleus, and gastrocnemius. Thus, [125I]adrenomedullin-binding sites in rat lung
      are abundant and can be differentiated from binding sites in rat heart, both
      pharmacologically and by mol wt.

PMID- 7720663
TI  - Interleukin-6 stimulates hepatic triglyceride secretion in rats.
AB  - Interleukin-6 (IL-6) not only regulates a variety of immune functions, but also
      is the most potent cytokine in inducing the hepatic acute phase proteins. We
      determined the effect of IL-6 on serum lipid levels and the mechanism of IL-6
      induced hypertriglyceridemia in rats. Intravenous administration of IL-6 (0.1-10
      micrograms/200 g BW) increased serum triglyceride levels in a dose-dependent
      manner. One hour after IL-6 administration, serum triglyceride levels were
      increased, with peak values at 2 h (2.2-fold increase). Serum cholesterol levels
      also increased, but the effect was delayed, first occurring at 4 h and peaking at
      8 h (1.24-fold increase). IL-6 treatment increased hepatic triglyceride secretion
      without decreasing the clearance of triglyceride-rich lipoproteins, indicating
      that the hypertriglyceridemia was due to increased secretion by the liver.
      Furthermore, IL-6 stimulates lipolysis, and the increased delivery of FFA to the
      liver significantly contributed to the IL-6-induced hypertriglyceridemia. Neither
      alpha 1- nor beta-adrenergic receptor antagonists affected the
      hypertriglyceridemia induced by IL-6, whereas previous studies have shown that
      endotoxin-induced hypertriglyceridemia was blocked by alpha-adrenergic receptor
      antagonists. These results demonstrate that IL-6 induces hypertriglyceridemia by
      stimulating hepatic triglyceride secretion independent of endogenous
      catecholamines. Thus, changes in hepatic triglyceride metabolism are another
      acute phase response that can be induced by IL-6.

PMID- 7720664
TI  - The growth hormone receptor messenger ribonucleic acid present in ovine fetal
      liver is a variant form.
AB  - Specific binding of ovine GH (oGH) to microsomal membranes isolated from fetal
      sheep liver is slight to nonexistent. The complementary DNA sequence encoding the
      oGH receptor (oGHR) has been reported, and Northern blot analysis has indicated
      that oGHR messenger RNA (mRNA) is present in fetal liver and skeletal muscle from
      mid- to late gestation. In human tissues, the GHR mRNA exists in multiple forms,
      including the deletion of exon 3 and variable 5'-untranslated regions. In
      rodents, the GHR mRNA exists in two forms, one encoding the membrane-bound
      receptor and the other encoding the soluble GH-binding protein. To further
      characterize the oGHR mRNA transcript present in ovine fetal liver during
      gestation, we designed a series of primers to be used in reverse transcriptase
      polymerase chain reactions (RT-PCR), which generate products that span from the
      5'-untranslated region through the coding region of the oGHR mRNA. Nucleotide
      sequences of the resulting complementary DNAs revealed that an oGHR mRNA is
      present from mid- to late gestation (days 60-135) which contains the region
      analogous to exon 3 of the human GHR gene. However, the 5'-untranslated region
      previously reported in adult tissues was not present until day 135 of gestation
      in fetal liver, nor was it present in day 100 fetal skeletal muscle. Northern
      hybridization analysis indicates that the major oGHR transcript in day 105 fetal
      liver is 5.8 kilobases (kb) in size, with minor transcripts observed at 4.7 kb
      and three transcripts greater than 6.5 kb. By day 135 of gestation, the
      transcript size is the same as that observed in day 100 pregnant ewe liver (5.5
      kb). We conclude that the oGHR mRNA present in midgestation fetal liver differs
      structurally from the transcript present in late gestation fetal liver and adult
      liver, and this difference may explain the lack of specific GH binding to ovine
      fetal liver membranes. Furthermore, our results suggest that there is a
      developmental switch in the structure of oGHR mRNA that occurs shortly before
      term, potentially preparing the fetus to respond to GH postnatally.

PMID- 7720665
TI  - Basic fibroblast growth factor stimulates expression of interstitial collagenase
      and inhibitors of metalloproteinases in rat bone cells.
AB  - Basic fibroblast growth factor (bFGF) is a bone cell mitogen that affects
      osteoblastic function by suppressing type I collagen synthesis. The investigators
      in this study examined whether bFGF also regulates interstitial collagenase and
      tissue inhibitors of metalloproteinases (TIMPs) in osteoblast-enriched cells
      isolated from 22-day fetal rat calvariae. After exposure to 600 pM bFGF,
      interstitial collagenase messenger RNA (mRNA) levels, as determined by Northern
      hybridization analysis, increased after 2 h and were maximally stimulated to
      approximately 13-fold at 6 h. Exposure of osteoblast-enriched cells to 0.06-6 nM
      bFGF increased collagenase mRNA in a dose-dependent manner, and bFGF also
      increased immunoreactive collagenase measured in the culture medium by Western
      blot analysis. The protein synthesis inhibitor cycloheximide, as well as two
      inhibitors of protein kinase C, staurosporine and sangivamycin, prevented the
      bFGF induction of collagenase transcripts, whereas indomethacin, an inhibitor of
      prostaglandin synthesis, decreased the effect of bFGF on collagenase mRNA levels
      by about 50%. After exposure to 600 pM bFGF, levels of TIMP 1 and TIMP 3 mRNAs
      were also maximally stimulated to approximately 6-fold at 16 h and 4-fold at 6 h.
      bFGF did not modify TIMP 2 expression. In conclusion, bFGF may modulate
      degradation of collagenous bone matrix by inhibiting collagen as well as
      stimulating collagenase and TIMPs by osteoblasts.

PMID- 7720666
TI  - The immunoregulatory effects of prolactin in mice are time of day dependent.
AB  - The effects of timed administration of PRL on immune activities were investigated
      in male BALB/c mice. Ten daily injections of PRL (1 mg/kg) were made 0/24, 4, 8,
      12, 16, or 20 h after light onset (HALO). On day 11, spleen cells were harvested
      between 1-3 HALO and cocultured with gamma-irradiated C57BL/6 spleen cells for 5
      days, and proliferative responses to alloantigen were assayed (mixed lymphocyte
      reaction). When given in vivo at 4-12 HALO, PRL strongly stimulated proliferation
      by more than 2-fold, whereas PRL injections when given at 24 HALO substantially
      inhibited proliferation and had no effect when given at 16-20 HALO. When
      endogenous PRL secretion was stimulated for 7 days with injections of domperidone
      or 5-hydroxytryptophan, the splenocyte response increased by 48% and 64%,
      respectively, when injections were given at 9-10 HALO, but did not increase when
      they were given at 23-0 HALO. Inhibition of endogenous PRL secretion for 7 days
      with bromocriptine (2.5 mg/kg.day) inhibited splenocyte responsiveness by 40%
      when injected at 9 HALO, but had no effect when administered at 0 HALO.
      Furthermore, such bromocriptine treatment inhibited T- and B-cell mitogenic
      responses to Concanavalin-A (by 48%) and lipopolysaccharide (38%) when
      administered at 10, but not 0, HALO. In a manner similar to mixed lymphocyte
      reaction responses, daily PRL injections for 10 days at 11 HALO stimulated (40%)
      the in vivo delayed-type hypersensitivity response to antigen
      (azobenzenearsonate), whereas injections at 0 HALO were nonstimulatory.
      Bromocriptine treatment (1.5 mg/kg.day) suppressed the delayed-type
      hypersensitivity response (43% less than the control value) when administered at
      10-12 HALO, but had no effect when administered at light onset. Timed PRL
      injections for 28 days in adult mice increased (42%) the total thymic cell number
      when administered at 11 HALO, but had no effect when injected at 0 HALO.
      Together, these results show that immunocyte responsiveness to PRL is time of day
      dependent. Thus, these findings support an essential and heretofore unrecognized
      circadian role in PRL regulation of immunity.

PMID- 7720667
TI  - Calcium regulation of androgen receptor expression in the human prostate cancer
      cell line LNCaP.
AB  - Elevation of intracellular calcium levels in the presence of normal androgen
      levels has been implicated in apoptotic prostate cell death. Since the androgen
      receptor (AR) plays a critical role in the regulation of growth and
      differentiation of the prostate, it was of interest to determine whether Ca2+
      would affect the expression of androgen receptor messenger RNA (mRNA) and
      protein, thus affecting the ability of androgens to control prostate function. AR
      positive human prostate cancer cells, LNCaP, were incubated with either the
      calcium ionophore A23187 or the intracellular endoplasmic reticulum Ca(2+)-ATPase
      inhibitor thapsigargin. Subsequently, AR mRNA and protein levels were assessed by
      Northern and Western blot analysis. Both A23187 and thapsigargin were found to
      down-regulate steady state AR mRNA levels in a time- and dose-dependent manner.
      AR mRNA began to decrease after 6-8 h of incubation with 10(-6) M A23187 or 10(
      7) M thapsigargin, reaching a nadir at 16 and 10 h of incubation, respectively.
      In contrast, control mRNA (glyceraldehyde 3-phosphate dehydrogenase) did not
      change significantly during the treatments with either A23187 or thapsigargin. AR
      protein levels were found to be decreased after 12 h of incubation with either
      10(-6) M A23187 or 10(-7) M thapsigargin. The decrease in AR mRNA and protein
      seemed to precede apoptosis, since neither A23187 (24 h) nor thapsigargin (30 h)
      was found to alter cell morphology within the treatment time. Cycloheximide and
      actinomycin D were unable to change the calcium-mediated decrease in AR mRNA,
      ruling out the necessity for de novo protein synthesis or a change in mRNA
      stability. Moreover, the decrease in AR mRNA induced by calcium does not seem to
      involve protein kinase C- or calmodulin-dependent pathways, since inhibitors of
      these cellular components had no effect. Nuclear run-on assays demonstrated
      little or no effects of either A23187 or thapsigargin treatment on AR gene
      transcription (8 h and 10 h). In conclusion, these studies show that
      intracellular calcium seems to be a potent regulator of AR gene expression in
      LNCaP cells.

PMID- 7720668
TI  - Dehydration stimulates hypothalamic gene expression of histamine synthesis
      enzyme: importance for neuroendocrine regulation of vasopressin and oxytocin
      secretion.
AB  - Dehydration associated with hyperosmolality and decreased extracellular volume
      stimulates arginine vasopressin (AVP) and oxytocin (OT) secretion from
      magnocellular neurons of the hypothalamus. The effects of hyperosmolality and
      decreased extracellular volume on the magnocellular neurons are mainly indirect
      and seem to be mediated centrally via several neurotransmitters and
      neuropeptides. Because histamine (HA), which serves as a central
      neurotransmitter, releases AVP and OT from the neurohypophysis when administered
      centrally, we investigated the possible role of HA in dehydration-induced AVP and
      OT secretion. To do this, we studied 1) the effect of dehydration on messenger
      RNA (mRNA) expression of the HA synthesis enzyme, histidine decarboxylase (HDC),
      in the tuberomammillary nucleus of the hypothalamus; and 2) the effect of HA
      synthesis inhibition during dehydration on AVP and OT mRNA expression in the
      supraoptic nucleus of the hypothalamus as well as on plasma AVP and OT levels.
      Forty-eight hours of dehydration increased the mRNA level of HDC in the
      tuberomammillary nuclei, whereas 24 h of dehydration had no effect. Pretreatment
      with the HA synthesis inhibitor alpha-fluoromethylhistidine (alpha FMH) increased
      the expression of HDC mRNA in 24-h dehydrated rats, but had no effect in
      euhydrated rats. In rats dehydrated for 48 h, the already increased level of HDC
      mRNA was not increased further by alpha FMH. Twenty-four and 48 h of dehydration
      increased AVP and OT mRNA levels in the supraoptic nucleus. This effect was
      inhibited by alpha FMH pretreatment. Dehydration increased the plasma levels of
      AVP and OT to an extent which depended on the duration of dehydration.
      Pretreatment with alpha FMH inhibited the hormone responses to 24 h of
      dehydration, but did not affect the responses to 48 h of dehydration. Twenty-four
      and 48 h of dehydration had no significant effect on the contents of AVP and OT
      in the neurohypophysis, whereas pretreatment with alpha FMH combined with 48 h of
      dehydration led to depletion of AVP stores in the neurohypophysis. Based on the
      present findings, we conclude that hypothalamic histaminergic neurons are
      involved in the regulation of dehydration-induced stimulation of magnocellular
      AVP and OT neurons.

PMID- 7720669
TI  - Modulation of epidermal growth factor receptor interaction with the detergent
      insoluble cytoskeleton and its effects on receptor tyrosine kinase activity.
AB  - Previous reports have shown that the epidermal growth factor (EGF) receptor is
      associated with the detergent-insoluble actin cytoskeleton. To assess how this
      association can influence receptor function, EGF-stimulated protein-tyrosine
      kinase activity was examined in the detergent-soluble and -insoluble
      (cytoskeletal) fractions of human A431 epidermoid carcinoma cells. EGF receptor
      extraction was optimal using 0.15% Triton X-100, and higher detergent
      concentrations did not significantly increase the amount of solubilized receptor
      as assessed by immunoblotting. Normalization of EGF-stimulated tyrosine kinase
      activity on the basis of receptor mass revealed that the specific activity of the
      cytoskeletal (0.15% Triton-insoluble) fraction is nearly 3-fold greater than that
      of the soluble receptor when using angiotensin II as the peptide substrate. The
      increased specific activity of the Triton-insoluble receptor suggests that
      interaction with the cytoskeleton can facilitate maximal kinase activity. This
      hypothesis is supported by the observation that, when compared with the soluble
      EGF receptor, the receptor in the cytoskeletal fraction demonstrates a 15-fold
      more favorable apparent Michaelis-Menten constant for ATP and a 4-fold more
      favorable Michaelis-Menten constant for angiotensin II. Although the cytoskeletal
      EGF receptor seems to represent less than 10% of the total receptor mass in cells
      not exposed to EGF, these data indicate that it comprises a highly active
      receptor pool. To examine the regulation of receptor association with the
      detergent-insoluble fraction, A431 cells were treated at 37 C with EGF for up to
      5 h, or with the phorbol ester 12-phorbol 12-myristate 13-acetate for 1 h, and
      total receptor mass and distribution were determined. In these studies, total
      immunodetectable receptor decreased significantly after 20 min of EGF
      administration, whereas the population of Triton-insoluble receptors increased
      within 40 min to greater than four times that observed before EGF addition and
      remained at that level for the full 5 h of EGF treatment. Conversely, 12-phorbol
      12-myristate 13-acetate treatment, which is known to down-regulate high affinity
      EGF binding, had little effect on receptor association with the cytoskeletal
      fraction. In sum, these data indicate the presence of a highly active
      subpopulation of cytoskeletally associated EGF receptors that can be up-regulated
      during long-term (5 h) ligand exposure.

PMID- 7720670
TI  - Aldosterone and dexamethasone both stimulate energy acquisition whereas only the
      glucocorticoid alters energy storage.
AB  - Corticosteroids stimulate and insulin inhibits energy acquisition (food intake);
      conversely, corticosteroids inhibit and insulin stimulates energy storage (body
      weight gain). Thus, together these hormones mediate long-term energy balance.
      This study tested whether the stimulatory action of corticosteroids on food
      intake was mediated by association with high affinity mineralocorticoid receptors
      (MRs) or lower affinity glucocorticoid receptors (GRs). Young male rats were
      adrenalectomized (ADX) and given vehicle (control) or streptozotocin (diabetic);
      subgroups of rats were infused with vehicle, aldosterone (Aldo, an MR agonist in
      vivo), dexamethasone (Dex, a GR agonist in vivo), or Aldo&Dex for the 5 days
      after ADX. Sham-ADX rats were included. Food intake, body weight gain, and
      epididymal white adipose and interscapular brown adipose tissue stores were
      weighed. ADX decreased food intake by approximately 24%, and food intake was not
      increased by diabetes as it was in sham-ADX rats. In control ADX rats, Dex, but
      not Aldo, stimulated insulin, and food intake was not significantly affected by
      either hormone; together, Aldo and Dex restored insulin and food intake to sham
      ADX rats. Food intake in diabetic ADX rats was significantly increased by each
      treatment (ADX < Aldo < Dex < Aldo&Dex = sham). Aldo increased body weight
      through an increase in fluid volume (estimated by decreased plasma protein
      concentration); however, fat stores were not different from ADX. Dex reduced body
      weight in control rats but maintained fat stores; in diabetic rats, body weight
      and fat stores were less than or similar to ADX. We conclude that: 1)
      corticosteroids, acting through association with both MRs and GRs, stimulate food
      intake; 2) insulin counteracts the GR-mediated stimulation of food intake in
      control rats; and 3) Dex and insulin, which is stimulated by Dex, selectively
      maintain or increase body fat stores, probably at the expense of protein stores.

PMID- 7720671
TI  - Estrogen target tissue determines alternative promoter utilization of the human
      estrogen receptor gene in osteoblasts and tumor cell lines.
AB  - The estrogen receptor (ER) mediates the effects of its cognate ligand on
      important cellular processes such as development of female secondary sexual
      characteristics, establishment and maintenance of pregnancy, progression of
      breast cancer, and maintenance of bone mass. We have previously demonstrated that
      the human ER (hER) gene is transcribed from two promoters, suggesting that tissue
      and cell-specific expression patterns of this gene may, at least in part, be
      regulated by differential promoter usage. Here we show, by using a reverse
      transcriptase coupled polymerase chain reaction assay, that transcripts initiated
      from both hER gene promoters were expressed in breast and uterus. In contrast,
      only transcripts originating from the distal promoter could be detected in human
      primary osteoblasts. Furthermore, determination of the expression levels of the
      two hER transcripts by quantitative polymerase chain reaction demonstrated an
      almost 30-fold increase of the transcripts originating from the proximal promoter
      in breast cancer cell lines over that detected in normal breast tissue. Taken
      together, our results demonstrate a previously unrecognized mechanism for
      regulation of hER gene expression by tissue-specific differential promoter
      utilization. In addition, our results suggest that estrogen-dependent cell
      transformation may be accompanied by a change in the relative expression levels
      of the two hER transcripts.

PMID- 7720672
TI  - Rapid activation of rat insulin-like growth factor-I gene transcription by growth
      hormone reveals no changes in deoxyribonucleic acid-protein interactions within
      the second promoter.
AB  - Insulin-like growth factor-I (IGF-I) is a highly conserved 70-residue circulating
      peptide that mediates many of the systemic growth-promoting effects of GH. This
      laboratory has found previously that GH rapidly stimulates hepatic IGF-I
      transcription in hypophysectomized (hypox) rats by activating promoter 1, the
      major rat IGF-I gene promoter. In this study, the hormonal regulation of IGF-I
      expression through promoter 2, a minor promoter in most tissues but active in the
      liver, was investigated. Through use of a sensitive RNase protection assay, GH
      was shown to rapidly induce the accumulation of correctly initiated transcripts
      directed by this promoter in hepatic nuclei. Using in vitro DNase-I footprinting,
      six DNA-protein interactions were identified within promoter 2 with hepatic
      nuclear extracts from juvenile male hypox rats given a single ip injection of GH
      or saline 60 min before death. These DNA-protein-binding complexes also were
      investigated for specificity and for regulation by GH by gel mobility shift
      assays. All DNA-protein interactions were detected in hepatic nuclear protein
      extracts from hypox rats and did not change within 15-120 min after GH treatment.
      These results thus identify and characterize a series of constitutive nuclear
      protein-binding sites within the second rat IGF-I promoter that may be involved
      in mediating its transcriptional activity.

PMID- 7720673
TI  - Intracellular Ca(2+)-activated K+ channels modulated by variations in
      extracellular Ca2+ in dispersed bovine parathyroid cells.
AB  - The modulation of K+ channels by Ca2+ may have important functional implications
      in parathyroid cells, since in most endocrine cells they control membrane voltage
      regulating Ca2+ influx and hormone secretion. To characterize specific channel
      mechanisms regulating membrane voltage in parathyroid cells, the patch-clamp
      technique was used to determine the activities of K+ channels at different levels
      of intracellular Ca2+ concentration (Ca2+i) associated with changes in
      extracellular Ca2+ concentration (Ca2+o). This study shows that the membranes of
      dispersed bovine parathyroid cells contain a K+ channel that is activated by
      elevated Ca2+o through an indirect mechanism (i.e. exposure of the entire cell to
      high Ca2+o activates the channel despite a low Ca2+ concentration within the
      pipette solution on the external side of the channel under study). This K+
      channel has a unitary conductance of 191 pS and is highly selective for K+,
      similar to the so-called maxi type of Ca(2+)-activated K+ channel previously
      defined in a number of other cell types. Like the latter channel, the activity of
      this channel in excised patches from parathyroid cells is markedly increased when
      an EGTA-containing buffer on the cytoplasmic face of the membrane is replaced
      with one containing 0.5 microM Ca2+. Changes in Ca2+ on the intracellular side of
      the membrane also shift the level of voltage necessary for half-maximal
      activation of the channel from 103 mV at 0.1 microM Ca2+ to 79 mV and 54 mV at
      0.25 and 0.5 microM Ca2+, respectively. When similar studies were carried out
      using cell-attached patches on parathyroid cells exposed to 0.5, 1.5, or 2.0 mM
      Ca2+o, the values for half-maximal activation were approximately 105, 56, and 29
      mV, respectively. The latter result suggests that in intact parathyroid cells,
      the channel is exposed to Ca2+i concentrations of about 0.15-0.2, 0.4 and 0.6-0.7
      microM at these three extracellular Ca2+ concentrations, values that are in
      excellent agreement with those previously measured using Ca(2+)-sensitive
      fluorescent dyes. Thus, parathyroid cells express a maxi type of Ca(2+)-activated
      K+ channel that is indirectly regulated by Ca2+o, presumably through concomitant
      changes in Ca2+i. The latter may limit the extent of the cellular depolarization
      produced in response to elevated Ca2+o in this cell type.

PMID- 7720674
TI  - The "VGF" protein in rat adenohypophysis: sex differences and changes during the
      estrous cycle and after gonadectomy.
AB  - Gene expression and cell localization of the neuroendocrine protein VGF were
      studied in the rat anterior pituitary. In females, four antisera against
      nonoverlapping regions of VGF immunostained a small number of lactotropes and
      many gonadotropes. In the latter cells, VGF immunoreactivity was localized to a
      subpopulation of secretory granules. Distinct changes were seen after estrus,
      with a significant increase in VGF messenger RNA (whole pituitary), whereas VGF
      immunostaining was strikingly reduced in gonadotropes and somewhat more abundant
      in lactotropes. In male rats, gene expression was low, and immunoreactivity was
      restricted to a few lactotropes. After castration or ovariectomy, VGF messenger
      RNA was high, and VGF immunoreactivity was abundant in gonadotropes. Selective
      localization and cyclic modulation suggest involvement of the VGF gene product(s)
      in pituitary gonadotrope and/or lactotrope function.

PMID- 7720675
TI  - Phorbol ester-induced alteration in the pattern of secretion and storage of
      chromogranin A and neurotensin in a human pancreatic carcinoid cell line.
AB  - Brief phorbol ester treatment of BON cells results in a persistent release and
      cellular depletion of immunoreactive chromogranin A (CGA-IR) and neurotensin (NT
      IR) cell contents. The purpose of the present study was to characterize the
      effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on the secretion,
      biosynthesis, and steady-state messenger RNA (mRNA) levels of chromogranin A
      (CGA) and of a coresident peptide, neurotensin, by a novel human pancreatic
      carcinoid cell line, called BON. Acute TPA treatment (100 nM, 1 h) of BON cells
      resulted in 20- and 40-fold elevations in release of CGA-IR and NT-IR,
      respectively; and a 70-90% depletion of CGA-IR and NT-IR cell contents. TPA
      treatment also increased the biosynthetic rate of CGA-IR. Steady-state mRNA
      levels of CGA and NT/N (neurotensin/neuromedin N) were unchanged. Cell contents
      of CGA-IR and NT-IR were not replenished for a period of up to 6 days; secretion
      of CGA-IR and NT-IR persisted. In addition, BON cells failed to release CGA in
      response to stimulation by ionomycin and A23187 several days after acute TPA
      treatment. Our data indicate that the lack of replenishment of cell contents of
      CGA-IR and NT-IR is not due to decreases in steady-state CGA-IR and NT-IR mRNA
      levels, nor is it due to a decrease in biosynthesis of CGA-IR, but it is the
      result of a loss in the ability of TPA-treated BON cells to store and secrete CGA
      IR and NT-IR in a regulated manner. These effects of TPA are mediated through the
      PKC pathway.

PMID- 7720676
TI  - Expression of nuclear hormone receptors in the rat supraoptic nucleus.
AB  - To investigate the role of nuclear hormone receptors on neuropeptide gene
      expression in the hypothalamo-neurohypophyseal system (HNS) of the rat, a survey
      was made of members of the nuclear hormone receptor superfamily that are
      expressed in the supraoptic nucleus (SON). A polymerase chain reaction cloning
      strategy based on homologies in the DNA-binding domain of AGGTCA-binding factors
      was devised for the identification of receptors in microdissected SON tissue.
      Cloning of the amplified products led to the identification of five true
      receptors, thyroid hormone receptor-alpha (THR alpha), retinoic acid receptor
      alpha, retinoic acid receptor-gamma, retinoid X receptor-alpha, and retinoid X
      receptor-gamma, as well as four orphan receptors, apolipoprotein AI regulatory
      protein (ARP-1), chicken ovalbumin upstream promoter transcription factor I (COUP
      TF I), estrogen-related receptor 2, and testis receptor 4 (TR4). Dot-blot
      screening of amplified gene fragment analysis showed that THR alpha, ARP-1, TR4,
      and COUP-TF I were the most abundant factors expressed in the SON region, in the
      order THR alpha > ARP-1 > TR4 approximately COUP-TF I. THR alpha has previously
      been localized to HNS neurons. In situ hybridization analysis showed that ARP-1,
      COUP-TF I, and TR4 were not expressed in magnocellular neurons at appreciable
      levels, but rather in surrounding structures. Furthermore, in lactating female
      rats there were no significant differences in the composition of the nine
      identified nuclear hormone receptors in the SON region compared with control
      animals. From these experiments, it is concluded that there is a multitude of
      hypothalamically expressed nuclear hormone receptors, but that only THR alpha is
      expressed at relatively high abundance in HNS neurons. This indicates that the
      peptide-producing magnocellular neurons of the SON express a specific set of
      transcription factors of the nuclear hormone receptor family.

PMID- 7720677
TI  - Epidermal growth factor and transforming growth factor-alpha messenger
      ribonucleic acids and their receptors in the rat anterior pituitary: localization
      and regulation.
AB  - Evidence has shown that epidermal growth factor (EGF), transforming growth factor
      alpha (TGF alpha) and their receptors (EGF receptors) are present in the anterior
      pituitary, indicating that the growth factors are synthesized in situ and act
      locally. Studies have demonstrated that EGF could stimulate the hypothalamus
      pituitary-adrenal (HPA) cortex axis, particularly at the pituitary level in vivo
      and in vitro, and also stimulate TGF alpha messenger RNA (mRNA) expression in
      cultured bovine pituitary cells. Recently, our studies have demonstrated that
      some stresses up-regulated EGF mRNA expression in the anterior pituitary, as
      detected by ribonuclease protection assay, further indicating the possible roles
      of EGF in the stress response. However, little is yet known about the sources and
      targets (sites of EGF receptors) of the growth factors in the pituitary.
      Therefore, this study was designed to localize EGF and TGF alpha mRNA and their
      receptors as well as to assess the effects of cold stress (CS) on their
      expression in the subsets of pituitary cells. In situ hybridization
      immunocytochemistry coupled with immunocytochemistry and dual immunocytochemistry
      studies revealed the presence of 1) EGF mRNA in somatotropes and gonadotropes; 2)
      TGF alpha mRNA in somatotropes, gonadotropes, and lactotropes; and 3) EGF
      receptors in all subsets of pituitary cells. CS (30 min) induced the expression
      of EGF mRNA in corticotropes and thyrotropes. EGF expression was not altered in
      somatotropes and gonadotropes. No significant changes were detected in TGF alpha
      mRNA expression in the pituitary cells after 30 min of CS. Expression of EGF
      receptors was also increased after 30 min of CS. This resulted from increases in
      EGF receptor-labeled cells among thyrotropes and gonadotropes. The cold stress
      induced expression of EGF mRNA in corticotropes and thyrotropes fits with their
      overall activation after this type of stress. The increase in EGF receptor
      labeled cells among thyrotropes may point to an important autocrine role for EGF
      in maintaining TSH responses to cold. On the other hand, the significance of EGF
      receptor up-regulation in gonadotropes (FSH-containing cells) caused by CS
      remains unknown.

PMID- 7720678
TI  - Distribution of constitutive (HO-2) and heat-inducible (HO-1) heme oxygenase
      isozymes in rat testes: HO-2 displays stage-specific expression in germ cells.
AB  - The heme oxygenase isozymes, HO-1 and HO-2, oxidatively cleave the heme molecule
      to produce antioxidants, the bile pigments, the gaseous cellular messenger, CO,
      and iron, a regulator of transferrin, ferritin, and nitric oxide synthase gene
      expression. HO-1 (hsp32) is a stress-inducible enzyme, whereas HO-2 is
      constitutively expressed at high levels in the testes and brain. In the present
      study, using immunohistochemical and in situ hybridization techniques, we report
      for the first time the cellular distribution of HO-1 and HO-2 in the testes of
      normal and heat-shocked rats and define a cell-specific expression of the
      isozymes and a stage-specific expression of HO-2 in the organ. In normal tissue,
      HO-1 was present at low levels in the Sertoli cells and could not be detected in
      germ or Leydig cells. HO-2, on the other hand, was most prominently expressed in
      residual bodies and was not detected in spermatogonia. Modest levels of HO-2 were
      observed in spermatocytes, spermatids, and select Leydig cells. In contrast,
      prominent expression of HO-2 messenger RNAs (mRNAs) was detected by in situ
      hybridization in spermatogonia, as well as spermatocytes, spermatids, and
      residual bodies of the seminiferous epithelium. The expression pattern of HO-2
      protein and transcript in testes of heat-stressed (42 C; 20 min) rats did not
      differ from that in the control animals, whereas the expression pattern of HO-1
      differed from that in the controls, in which distinct populations of Leydig and
      Sertoli cells displayed intense immunoreactivity. Thermal stress also resulted in
      an increase (2.8-fold) in the testicular HO-1 mRNA level within 1 h after
      treatment, followed by a significant increase (32%) in total microsomal heme
      oxygenase activity 6 h after treatment. Notably, this increase followed a
      significant depression (36%) in enzyme activity, which was detected 1 h after
      hyperthermia. The disparity between HO-2 mRNA and protein distribution clearly
      indicates cell-specific differences in the translational efficiency of HO-2
      transcripts. It appears that HO-2 mRNA translation is linked to the maturation
      and expression of a factor(s) that regulates this process. This, in turn, appears
      to coincide with sperm development. HO-1 activity, on the other hand, which has a
      transcriptional component to its regulation, may have a role in maintenance of
      the conditions required for spermatogenesis.

PMID- 7720679
TI  - Growth hormone-releasing hormone in testicular interstitial and germ cells:
      potential paracrine modulation of follicle-stimulating hormone action on Sertoli
      cell function.
AB  - GH-releasing hormone (GHRH) is present in the interstitial and germ cells of the
      rat testis. In previous studies we found that GHRH is secreted from rat adult
      Leydig cells, in which it stimulates basal and LH-induced cAMP formation and
      steroidogenesis. In other studies cAMP production in Sertoli cells was found to
      be stimulated by GHRH. In the present report, we describe a potential paracrine
      action of GHRH in the Sertoli cell, with stimulation of cAMP formation in
      cultured adult and pubertal Sertoli cells. GHRH increased FSH-stimulated cAMP
      production in adult and pubertal cultures in a time-dependent manner. GHRH
      stimulation of basal and FSH-induced extracellular cAMP formation was more
      prominent in pubertal than in adult cultures. Immunocytochemical studies
      demonstrated the presence of GHRH-like immunoreactivity in rat interstitial cells
      from day 4 to adult life and in the acrosomal region of early and intermediate
      spermatids at stages III-VI of the seminiferous epithelium cycle. Immunoreactive
      GHRH was not observed in late spermatids and mature sperm or in Sertoli cells at
      any age. These results indicate that GHRH acts synergistically with FSH to
      promote cAMP production in Sertoli cells in culture. Testicular GHRH of Leydig
      and germ cell origin may be an important paracrine regulator of Sertoli cell
      function. Alternatively, GHRH present in germ cells may exert stage-specific
      intracrine functions.

PMID- 7720680
TI  - The effect of ovariectomy and estradiol replacement on brain-derived neurotrophic
      factor messenger ribonucleic acid expression in cortical and hippocampal brain
      regions of female Sprague-Dawley rats.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose
      etiology is presently unknown. Probably the most consistent and widespread
      deficit seen in this syndrome is that of the basal forebrain cholinergic system.
      We have previously demonstrated that estradiol (E2) modulates the function of
      these neurons and plays a role in their maintenance by preventing the ovariectomy
      induced decrease in choline acetyltransferase activity. It has been postulated
      that the lack of neurotrophic support may contribute at least in part to
      degeneration of cholinergic neurons in AD. As such, it is hypothesized that E2
      may affect cholinergic function by modulating the levels of certain neurotrophic
      factors. We have shown that 3 months after ovariectomy (OVX) there was a
      significant reduction in NGF messenger RNA (mRNA) levels. In the present study,
      we extended the hypothesis that E2 may serve a neurotrophomodulatory role by
      assessing the effect of OVX and E2 replacement on brain-derived nerve factor
      (BDNF) mRNA levels using in situ hybridization. BDNF mRNA levels were quantified
      in three groups of animals: ovary-intact animals, 28-week ovariectomized (OVX)
      animals, and E2-replaced OVX animals. Twenty-eight weeks after OVX, there were
      significant reductions in two of the three cerebral cortical regions analyzed
      [frontal (35%) and temporal (39%) cortexes], but E2 replacement was without
      effect. Twenty-eight weeks after OVX, there were also reductions in BDNF mRNA in
      all subregions of the hippocampus except CA1 (CA2 by 38%, CA3 by 44%, CA4 by 39%,
      and dentate gyrus by 37%), whereas E2 replacement was effective in elevating BDNF
      mRNA levels in the CA3, CA4, and dentate gyrus subregions. Collectively, the data
      demonstrate that E2 deprivation leads to a reduction in BDNF mRNA. Further, at
      the time point studied, E2 replacement is more effective in maintaining BDNF mRNA
      in the hippocampus than in the cortex, suggesting a regional difference in the
      ovarian steroid requirement for expression of BDNF.

PMID- 7720681
TI  - Coordinate regulation by diethylstilbestrol of the platelet-derived growth factor
      A (PDGF-A) and -B chains and the PDGF receptor alpha- and beta-subunits in the
      mouse uterus and vagina: potential mediators of estrogen action.
AB  - The effects of estrogen on the reproductive tract involve cell proliferation,
      migration, and differentiation, which need to be well coordinated. Polypeptide
      growth factors are believed to play a vital role in a number of these cellular
      processes. Among the growth factors now documented to be associated with estrogen
      action are epidermal growth factor, transforming growth factor-alpha (TGF alpha),
      transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, TGF beta 3, and
      insulin-like growth factor-I (IGF-I). Platelet-derived growth factors (PDGFs) are
      also potent mitogens, which consist of two peptide chains, denoted A and B, that
      dimerize to isoforms (PDGF-AA, -AB, and -BB) which differ in their functional
      properties, secretory behavior, receptor binding, and physiological effects. To
      study the role of the PDGF-A and -B chains and the PDGF receptor subunits, alpha
      and beta, during estrogen action in the mouse reproductive tract, time-dependent
      changes in the expression of these genes were examined by Northern and in situ
      RNA analyses and by immunohistochemistry after a single treatment of immature CD
      1 (17- to 19-day-old) mice with the synthetic estrogen, diethylstilbestrol (DES).
      Our results demonstrate estrogen modulation of the expression of messenger RNA
      (mRNA) and protein for the PDGF ligands and receptors in both the uterus and
      vagina of the mouse. Northern and in situ RNA analyses demonstrate time-dependent
      estrogen induction of the mRNA levels for these genes in both tissues within 3 h
      after treatment. However, distinctive mRNA expression profiles for the PDGF
      ligand and receptor genes are exhibited by the uterus and vagina in response to
      DES, especially in that the induction of transcripts for PDGF-A and both receptor
      subunits is more transient in the vagina than in the uterus. Steroid specificity
      studies demonstrate predominant estrogen-specific regulation of mRNA induction
      for these genes. Analysis of cell-specific RNA expression by in situ
      hybridization reveals prominent induction of transcripts for the PDGF chains and
      receptor subunits in the uterine and vaginal epithelium after estrogen treatment,
      although enhanced expression of mRNA is also noted in the stroma, particularly
      for the PDGF receptor subunit genes. Cellular localization of the PDGF ligand and
      receptor protein molecules by immunohistochemistry detected significant
      immunostaining for all of these proteins in both the uterus and vagina of control
      animals. After DES treatment, the uterus exhibits a significant decrease in the
      level of PDGF ligand and receptor proteins immunostained within 6 h, whereas less
      dramatic effects ar observed in the vagina.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7720682
TI  - Estradiol-17 beta and mu-opioid peptides rapidly hyperpolarize GnRH neurons: a
      cellular mechanism of negative feedback?
AB  - Control of the HPG axis involves a rapid (30 min) inhibition of LH (GnRH) release
      by E2. The time course of this effect is faster than expected for a purely
      transcriptional mechanism of E2 action. To elucidate the mechanism of E2 action,
      intracellular recordings in TTX were performed in guinea pig hypothalamic GnRH
      neurons. These neurons were directly hyperpolarized by both the mu-opioid
      agonist, DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol, 9 mV) and the GABAB agonist, baclofen
      (18 mV) by opening K+ channels. Schild analysis with naloxone (Ke = 2.4 nM)
      confirmed that mu-opioid receptors mediated the effect of DAMGO. E2 also directly
      hyperpolarized GnRH neurons by opening K+ channels. Coupled with previous work
      showing a rapid effect of E2 to alter mu-opioid potency (1), a model is presented
      in which E2 rapidly inhibits GnRH neurons through parallel, possibly synergistic
      pathways.

PMID- 7720683
TI  - Ceramide mediates tumor necrosis factor effects on P450-aromatase activity in
      cultured granulosa cells.
AB  - In [3H]serine-labelled granulosa cells treatment with TNF alpha (10 ng/ml)
      resulted in a transient decrease in cellular [3H]sphingomyelin and generation of
      [3H]ceramide that remained elevated 60 min later. In cells labelled with [methyl
      14C]choline, TNF alpha induced a similar reduction in [14C]sphingomyelin content
      that was accompanied by a sustained elevation in [14C]phosphorylcholine levels.
      In FSH-primed cells, TNF alpha inhibited P450-AROM activity in a dose-dependent
      manner, an effect that was also observed in cells treated with bacterial
      sphingomyelinase (SMase 0.003-0.3 U/ml) or increasing concentrations (0.1-10
      microM) of N-acetylsphingosine (C2-cer) a membrane-permeable analogue of
      ceramide. These results support the notion that sphingomyelin degradation to a
      bioeffector molecule ceramide, may be an early event involved in TNF alpha
      induced signal transduction in granulosa cells.

PMID- 7720684
TI  - A novel vasoactive peptide, adrenomedullin, inhibits pituitary
      adrenocorticotropin release.
AB  - The potent hypotensive peptide, adrenomedullin (AdM), originally isolated from a
      human pheochromocytoma is present in a variety of rat and human tissues. We
      examined its potential effects in anterior pituitary gland, reasoning that it may
      be a feedback regulator of adrenocorticotropin (ACTH) secretion. Rat AdM11-50
      inhibited basal ACTH secretion from dispersed, rat anterior pituitary cells in a
      significant, dose-related fashion (maximum inhibition at 10(-9) M). Rat AdM11-50
      also inhibited, in a dose-related fashion, corticotropin releasing hormone (CRH)
      stimulated ACTH secretion, but did not block the ability of CRH to stimulate cAMP
      accumulation in these cells. These findings suggest that in addition to
      peripheral actions in the vasculature and kidney, adrenomedullin may act within
      the anterior pituitary gland to control fluid and electrolyte homeostasis.

PMID- 7720685
TI  - Gel dependence of electrophoretic mobilities of double-stranded and viroid RNA
      and estimation of the contour length of a viroid by gel electrophoresis.
AB  - Double-stranded (ds) RNA normally exhibits a lower electrophoretic mobility than
      dsDNA having the same number of base pairs. This has been attributed to its net
      charge density that is lower than that of B-form DNA. But we show here that dsRNA
      runs faster than corresponding DNA in gels containing either > or = 2.5% agarose
      or > or = 8% acrylamide with high crosslinking (19:1 acrylamide:N,N'
      methylenebisacrylamide). However, the relative mobility of dsRNA as compared with
      DNA, extrapolated to 0% gel (0%T), remains constant (0.90 +/- 0.03) in all
      systems, in support of the charge density hypothesis. In comparison to dsRNA
      standards, the potato spindle tuber viroid, a small approximately 70% base-paired
      rod-like pathogenic RNA, is strongly retarded, presumably because of greater
      flexibility and/or stable curvature. Depending on the gel system, nonlinear
      extrapolation to 0% T leads to an apparent contour length of 140-230 bp, whereas
      130 +/- 20 bp can be determined from electron micrographs and 123-126 bp from
      secondary structure modeling. We attribute the variation of the electrophoretic
      behavior of both dsRNA and viroid RNA to interactions with the gel matrix.
      Nevertheless, extrapolation of the apparent contour length (in bp dsRNA)
      determined from low-crosslinked polyacrylamide gels (2.6%C) is comparable to the
      determination by alternative methods.

PMID- 7720686
TI  - Altered electrophoretic behavior of DNA due to short-time UV-B irradiation.
AB  - UV-B irradiation is often inevitable for visualization of DNA fragments after
      ethidium bromide staining. Three different simple-repeat-containing, double
      stranded genomic DNA fragments were analyzed for UV-B (312 nm) damage using
      different gel electrophoretic systems. The effects of UV-B light were obvious
      after 5 min (31.5 kJ/m2) of irradiation in native polyacrylamide gel
      electrophoresis (PAGE). Standard single-strand conformation analyses revealed no
      alterations while a modification did. Sodium dodecyl sulfate (SDS)-PAGE was found
      to be highly sensitive with regard to the detection of damages and their
      time/dosage dependency. In addition, SDS-PAGE analysis pointed to different
      events occurring during UV-B irradiation. Alterations in DNA conformation were
      detected in every single strand analyzed after 1 min (6.3 kJ/m2) of UV-B
      exposure. Gel retardation analyses revealed significant changes of protein
      binding to target DNAs after 2 min of irradiation--possibly stemming from
      structural modifications and/or originating from binding sites for proteins
      involved in DNA repair.

PMID- 7720687
TI  - Spatial and temporal depletion of ions from noncrosslinked denaturing
      polyacrylamide in capillary electrophoresis.
AB  - Electrical conductivity across a polyacrylamide-filled capillary decreases during
      the separation of DNA sequencing fragments. This conductivity decrease is
      localized to the first few centimeters at the injection (negative) end of the
      capillary; no conductivity change is noted at the detection (positive) end of the
      capillary. The zone of decreased conductivity extends further into the capillary
      as the separation proceeds. The zone is most important for freshly prepared
      capillaries; capillaries used nine days after polymerization generate an
      insignificant current drop. The data are consistent with ionic depletion due to
      differences in transport numbers between the separation medium and the buffer
      reservoirs.

PMID- 7720688
TI  - Capillary electrophoresis separation of oligosaccharides: I. Effect of
      operational variables.
AB  - The influence of operating variables on the separation of labeled oligosaccharide
      molecules in capillary electrophoresis with polymer networks is presented. In
      this study, an equation was derived that relates the effects of electrophoresis
      variables such as field strength, temperature, molecular weight and gel
      concentration to the migration velocity. As a model system, 8-aminonaphthalene
      1,3,6-trisulfonate ANTS-labeled wheat starch digest was examined to show the
      validity of the equation. As an illustration of the high resolving power
      achievable with capillary electrophoresis, oligosaccharide molecules up to the
      degree of polymerization of 25 were separated with the very high efficiency of N
      > 10(6) and efficiency generation rate of 3500 plates/m/s for maltose. Separation
      based on the size of the oligosaccharides was not obtained with either entangled
      or unentangled polymer solutions.

PMID- 7720689
TI  - Consequences of a maximum existing in the dependence of separation selectivity on
      concentration of cyclodextrin added as chiral selector in capillary zone
      electrophoresis.
AB  - The maximum in the dependence of the separation selectivity on the concentration
      of cyclodextrin may be utilized for the determination of the mean value of host
      guest interaction constants of the separated enantiomers. For the hosting of N-t
      BOC-DL-tryptophan by beta-cyclodextrin, the mean value of these constants, found
      by drop line estimated from the cyclodextrin concentration corresponding at the
      maximum, is 350 L.mol-1. The separation at this concentration of cyclodextrin
      offers the highest resolution in the shortest separation time. It is shown that
      commonly used simple preliminary experiments, testing the capability of a
      cyclodextrin to resolve chiral compounds, and based on relatively high
      cyclodextrin concentrations, may easily lead to incorrect conclusions in cases of
      enantiomers strongly interacting with the cyclodextrin used.

PMID- 7720690
TI  - Capillary zone electrophoresis with indirect photometric detection in the visible
      range.
AB  - Sensitivity and applicability of commonly used indirect photometric detection in
      the UV region can be adversely affected by the absorption of the UV light by
      detected solutes and/or by matrix constituents migrating with them. If the
      visible light is exploited instead of the UV light, both these disadvantages may
      be for the most part eliminated, and, moreover, the indirect photometric
      detection will extend its versatility and sensitivity. Prospects as well as main
      problems of the approach were tested using inorganic ions as analytes. If organic
      dyes with a molar light absorption coefficient of the order of 10(6) mol-1 L m-1
      was selected as the light-absorbing constituents of the background electrolyte,
      detection sensitivity comparable with the best reported results was reached for
      anions; for cations, the detection limit was even lower by two orders of
      magnitude.

PMID- 7720691
TI  - Focusing of alkaline proteases (subtilisins) in pH 10-12 immobilized gradients.
AB  - Isoelectric focusing in very alkaline immobilized pH gradients (IPG) was adopted
      for checking the purity and assessing the pI value of two strongly alkaline
      proteases: Savinase and Durazym. The first enzyme (known to be the most alkaline)
      contains 5 Asp, 5 Glu, 7 His, 7 Tyr, 5 Lys, no Cys and 8 Arg residues and should
      have a theoretical pI of 9.7. Yet, when focused in a pH 9-11 IPG interval, it was
      lost in the cathodic compartment. After repeated attempts at creating even more
      alkaline pH intervals, a pH 10-12 IPG range was finally optimized and proved
      successful in focusing both enzymes midway between the two electrodic
      compartments. The pI of Savinase was measured as 11.15 +/- 0.15; that of Durazym
      as 10.95 +/- 0.20 and that of the pI marker cytochrome c as 10.6 +/- 0.17. Both
      enzymes (and a number of minor components in each preparation) were proven to be
      active by an in situ zymogram consisting of a casein/agar overlay. The
      discrepancy between theoretical and experimental pI values could not be fully
      reconciled: when correcting for pK values of amino acids in proteins at 10
      degrees C, instead of the tabulated values at 25 degrees C, the pI should
      increase to a value of 10. Differential UV spectra showed that ca. 1/2 Tyr are
      buried in the protein interior and are thus unable to contribute to surface
      charge. This further increases the pI value by 0.3 pH units to a value of 10.3,
      still quite removed from the experimentally assessed pI value (in the gel, at 10
      degrees C) of 11.15.

PMID- 7720692
TI  - Isoelectric focusing in immobilized pH gradient of melon (Cucumis melo L.) seed
      protein: methodical and genetic aspects, and application in breeding.
AB  - Genetic variability of melon seed proteins was studied by separation of seed
      protein by isoelectric focusing in immobilized pH gradient (IEF-IPG) under
      denaturing conditions. A routine procedure was developed for IEF-IPG of hundreds
      of individual melon seeds per day. A group of 74 accessions from 19
      morphologically distinct groups and from different geographic origin were studied
      by IEF-IPG using pH gradients of 4-10, 4-7 and 6-10. The electrophoretic analysis
      of the 74 accessions showed 270 reproducible seed protein bands of which 70 were
      variable. Genetic evaluation led to the conclusion that at least 20 loci govern
      the variation found. The phylogenetic trees constructed using the protein data on
      one hand and the morphological data on the other hand were compared and their use
      was evaluated. A number of commercial Cantaloup F1 hybrid descendants derived
      from the F1 hybrids by diplohaploidization or single plot descent were studied by
      IEF-IPG using pH gradients of 4-7 and 6-10. Among the F1 hybrids and their
      descendants 265 reproducible protein bands could be identified of which 72 were
      variable as to presence versus absence. The genetic interpretation of the protein
      pattern as found by IEF-IPG and the use of IEF-IPG in plant breeding was
      discussed. It was concluded that IEP-IPG of melon seed proteins is a valuable
      tool in breeding.

PMID- 7720693
TI  - Response of bacteria and fungi to high-pressure stress as investigated by two
      dimensional polyacrylamide gel electrophoresis.
AB  - In an attempt to generalize previous observations (Jaenicke et al., Appl.
      Environ. Microbiol. 1988, 54, 2375-2380) and to find a convenient model system
      for studies of the pressure response, we tested the suitability of Escherichia
      coli and Thermotoga maritima (bacteria), and of five different eukaryotic species
      including the filamentous fungi Asteromyces cruciatus and Dendryphiella salina,
      and the marine yeasts Debaryomyces hansenii, Rhodosporidium sphaerocarpum, and
      Rhodotorula rubra. Using two-dimensional polyacrylamide gel electrophoresis,
      detailed investigations on the pressure response were carried out with E. coli
      and Rhodosporidium sphaerocarpum. In the former organism, major pressure response
      proteins could not be detected, although there are significant differences in
      expression of some proteins as well as some minor components that are found in
      all of the high pressure cell extracts but not in extracts from cultures grown at
      atmospheric pressure. In Rhodosporidium sphaerocarpum, no change in protein
      expression patterns was observed between 0.1 and 20 MPa. However, approaching the
      limit of viability of 50 MPa, additional protein spots became detectable at 45
      MPa. This finding correlates with the observation of abnormal growth forms of the
      organism at this pressure (Lorenz, R. et al. manuscript in preparation).

PMID- 7720694
TI  - Protein studies of human non-Hodgkin's B-lymphoma: appraisal by two-dimensional
      gel electrophoresis.
AB  - We have utilized two-dimensional polyacrylamide gel electrophoresis (2-D PAGE)
      coupled with silver stain to identify cellular proteins in human non-Hodgkin's B
      lymphoma (NHL). Five cell lines (SKDHL2B, WSU-DLCL2, WSU-NHL, WSU-FSCCL and
      SKLN1), representing four different NHL maturational stages and a normal Epstein
      Barr virus (EBV)-transformed line of B-cell origin (SKLN1) were studied. The NHL
      lines were immunophenotyped using flow cytometry with lineage associated
      monoclonal antibodies. Whole cell lysates of the cell lines were subjected to 2-D
      PAGE analyses. The gels were analyzed with an image scanning computer and the
      qualitative differences of protein patterns were studied. Results revealed great
      similarities in patterns of the NHL lines. A master map containing common NHL
      protein spots was constructed. When the map of each tumor line was compared to
      the master map, several protein spots were associated with each NHL-grade. Search
      for these proteins in the normal EBV-transformed B-cell line showed that only one
      of the proteins (S3; M(r)/pI 19/5.9) was present. Proteins that were detected in
      malignant NHL, but not in the normal EBV-line, could provide important
      information regarding the human NHL B-lymphocyte data-bases. Whether or not these
      proteins are definite malignant markers to distinguish between different NHL
      maturational stages needs further exploration through electroblotting and
      microsequencing.

PMID- 7720695
TI  - Quantification of silver-stained proteins resolved by two-dimensional
      electrophoresis: genetic variability as related to abundance and solubility in
      two maize lines.
AB  - Relative abundance and solubility of proteins from etiolated coleoptiles of maize
      were investigated using two-dimensional electrophoresis (2-D PAGE). Automatic
      quantification of silver-stained polypeptides on replicate 2-D gels made it
      possible to test the linearity of the relationship between spot integrated
      optical density and protein amount in the range from 15 micrograms to 135
      micrograms per gel, in two inbred lines. A linear response was found for more
      than 60% of the spots in each genotype. When a linear response was found in both
      lines for a given spot, the slope values were similar in 94% of the cases,
      indicating the reliability of silver staining for polypeptide quantification. The
      parameters of the curves allowed the definition of protein classes of different
      abundances that could be compared for genetic variability between the two lines.
      From a comparison between standard 2-D patterns (trichloroacetic acid-acetone
      extracted proteins) and patterns obtained from Tris buffer extracted proteins, it
      appeared that 92% of the proteins visualized in the standard gels were soluble.
      No difference in genetic variability, either qualitative or quantitative, was
      evidenced between the various classes of abundance, or between soluble and
      insoluble proteins.

PMID- 7720696
TI  - A role of Sep1 (= Kem1, Xrn1) as a microtubule-associated protein in
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae cells lacking the SEP1 (also known as XRN1, KEM1, DST2,
      RAR5) gene function exhibit a number of phenotypes in cellular processes related
      to microtubule function. Mutant cells show increased sensitivity to the
      microtubule-destabilizing drug benomyl, increased chromosome loss, a karyogamy
      defect, impaired spindle pole body separation, and defective nuclear migration
      towards the bud neck. Analysis of the arrest morphology and of the survival
      during arrest strongly suggests a structural defect accounting for the benomyl
      hypersensitivity, rather than a regulatory defect in a checkpoint. Biochemical
      analysis of the purified Sep1 protein demonstrates its ability to promote the
      polymerization of procine brain and authentic S.cerevisiae tubulin into flexible
      microtubules in vitro. Furthermore, Sep1 co-sediments with these microtubules in
      sucrose cushion centrifugation. Genetic analysis of double mutant strains
      containing a mutation in SEP1 and in one of the genes coding for alpha- or beta
      tubulin further suggests interaction between Sep1 and microtubules. Taken
      together these three lines of evidence constitute compelling evidence for a role
      of Sep1 as an accessory protein in microtubule function in the yeast
      S.cerevisiae.

PMID- 7720697
TI  - Ser/Thr-rich repetitive motifs as targets for phosphoglycan modifications in
      Leishmania mexicana secreted acid phosphatase.
AB  - The insect stage of the protozoan parasite Leishmania mexicana secretes a
      phosphomonoesterase in the form of a filamentous complex. The polypeptide
      subunits of this polymer are modified by phosphoglycans and/or oligomannosyl
      residues linked to phosphoserine. Based on peptide sequence data of a predominant
      100 kDa protein of the filamentous complex, two tandemly arranged, single copy
      genes, lmsap1 and lmsap2, were cloned and sequenced. lmsap1 predicts a protein
      with features characteristic of acid phosphatases and a remarkable serine- and
      threonine-rich region of 32 amino acids close to the C-terminus. In the otherwise
      identical lmsap2 product, this region is extended to 383 amino acids and is
      composed of short Ser/Thr-rich repeats. Deletion analysis demonstrates that
      lmsap1 encodes the major 100 kDa protein of the complex while a minor 200 kDa
      component is derived from the lmsap2 gene. Null mutants of either gene retain the
      ability to secrete acid phosphatase filaments, while a deletion of both genes
      results in Leishmania defective in enzyme formation. The Ser/Thr-rich domains are
      the targets for phosphoglycan modifications as shown by the expression of
      secreted fusion proteins composed of these C-terminal regions and the N-terminal
      domain of a lysosomal acid phosphatase.

PMID- 7720698
TI  - Stimulation of single L-type calcium channels in rat pituitary GH3 cells by
      thyrotropin-releasing hormone.
AB  - Hormonal stimulation of voltage-dependent Ca2+ channels in pituitary cells is
      thought to contribute to the sustained phase of Ca2+ entry and secretion induced
      by secretion stimulating hormones and has been suggested as a mechanism for
      refilling the Ca2+ stores. Using the cell-attached patch-clamp technique, we
      studied the stimulation of single Ca2+ channels by thyrotropin-releasing hormone
      (TRH) in rat GH3 cells. We show that TRH applied from the bath switched the
      activity of single L-type Ca2+ channels from a gating mode with very low open
      probability (po) to a gating mode with slightly smaller conductance but 10 times
      higher po. Interconversions between these two gating modes were also observed
      under basal conditions, where the equilibrium was shifted towards the low po
      mode. TRH applied from the pipette had no effect, indicating the involvement of a
      cytosolic compound in the stimulatory pathway. We show that TRH does not
      potentiate all the L-type Ca2+ channels in a given membrane patch and report
      evidence for co-expression of two functionally different L-type Ca2+ channels.
      Our results uncover the biophysical mechanism of hormonal stimulation of voltage
      dependent Ca2+ channels in GH3 cells and are consistent with differential
      modulation of different subtypes of dihydropyridine-sensitive Ca2+ channels.

PMID- 7720699
TI  - Structure and functional expression of a new member of the tetrodotoxin-sensitive
      voltage-activated sodium channel family from human neuroendocrine cells.
AB  - A member of a new subclass of the voltage-activated sodium channel genes has been
      cloned from the human medullary thyroid carcinoma (hMTC) cell line. The cDNA of
      hNE-Na (human neuroendocrine sodium channel) encodes a 1977 amino acid protein
      which phylogenetically represents a link between sodium channels isolated from
      skeletal muscle and brain. The hNE-Na alpha subunit was transiently expressed in
      human embryonic kidney cells either alone or in combination with the human sodium
      channel beta 1 subunit. The channel exhibited rapid activation and inactivation
      kinetics, and was blocked by tetrodotoxin and cadmium with IC50 values of 24.5 nM
      and 1.1 mM, respectively. Action potentials were generated in cells expressing
      high levels of hNE-Na. Northern blot and reverse transcription-polymerase chain
      reaction (RT-PCR) analyses demonstrated its expression in hMTC cells, in a C-cell
      carcinoma, and in thyroid and adrenal gland. Transcripts were not identified in
      pituitary gland, brain, heart, liver or kidney, indicating that the hNE-Na is a
      sodium channel solely expressed in neuroendocrine cells.

PMID- 7720700
TI  - In vivo iodination of a misfolded proinsulin reveals co-localized signals for Bip
      binding and for degradation in the ER.
AB  - The signal for degradation of proteins in the endoplasmic reticulum (ER) is
      thought to be the exposure of internal domains which are buried when the protein
      has adopted its correct conformation and which are also exposed in assembly
      intermediates. This raises the question of why the intermediates are not
      degraded. We developed a system based on the peroxidase-catalyzed iodination of
      tyrosine residues which continuously monitors the exposure of internal domains of
      proinsulin. In CHO cells this system discriminated between assembly intermediates
      of wild type (wt) proinsulin and misfolded proinsulin, as shown by the exclusive
      iodination of a misfolded mutant which was finally degraded in the ER. Iodination
      in vitro showed that the assembly intermediates of wt proinsulin also exposed
      internal domains. This iodination was inhibited by the addition of the molecular
      chaperone Bip which was co-immunoprecipitated with proinsulin in CHO cells. The
      results obtained with the mutant proinsulin support the assumption that exposed
      internal domains represent the signal for degradation in the ER. Observations of
      wt proinsulin show that Bip masks internal domains of normal assembly
      intermediates during the entire assembly process, thereby suppressing their
      degradation. We propose that internal domains contain co-localized signals for
      Bip binding and for degradation.

PMID- 7720701
TI  - 'Sheltered disruption' of Neurospora crassa MOM22, an essential component of the
      mitochondrial protein import complex.
AB  - MOM22 is a component of the protein import complex of the mitochondrial outer
      membrane of Neurospora crassa. Using the newly developed procedure of 'sheltered
      disruption', we created a heterokaryotic strain harboring two nuclei, one with a
      null allele of the mom-22 gene and the other with a wild-type allele. Homokaryons
      bearing the mom-22 disruption could not be isolated, suggesting that mom-22 is an
      essential gene. The mutant nucleus can be forced to predominate in the
      heterokaryon through the use of specific nutritional and inhibitor resistance
      markers. Cultivation of the heterokaryon under conditions favoring the mutant
      nucleus resulted in selective depletion of MOM22. MOM22-depleted cells did not
      grow and contained mitochondria with an altered morphology and protein
      composition. Protein import into isolated, MOM22-depleted mitochondria was
      abolished for most precursor proteins destined for all subcompartments. In
      contrast, precursors of MOM19, MOM22 and MOM72 became inserted normally into the
      outer membrane, defining a novel MOM22-independent import pathway which remained
      intact in mutant mitochondria. Furthermore, the specific binding of the ADP/ATP
      carrier to the outer membrane was unaffected, but subsequent transport across the
      outer membrane did not occur. Our data show that MOM22 is an essential component
      of Neurospora cells specifically required for the biogenesis of mitochondria.

PMID- 7720702
TI  - Protein kinase C regulates MARCKS cycling between the plasma membrane and
      lysosomes in fibroblasts.
AB  - MARCKS is a protein kinase C (PKC) substrate that is phosphorylated during
      neurosecretion, phagocyte activation and growth factor-dependent mitogenesis.
      MARCKS binds calcium/calmodulin and crosslinks F-actin, and both these activities
      are regulated by PKC-dependent phosphorylation. We present evidence here that PKC
      dependent phosphorylation also regulates the cycling of MARCKS between the plasma
      membrane and Lamp-1-positive lysosomes. Immuno-fluorescence and immunoelectron
      microscopy, and subcellular fractionation, demonstrated that MARCKS was
      predominantly associated with the plasma membrane of resting fibroblasts.
      Activation of PKC resulted in MARCKS phosphorylation and its displacement from
      the plasma membrane to Lamp-1-positive lysosomes. MARCKS phosphorylation is
      required for its translocation to lysosomes since mutating either the serine
      residues phosphorylated by PKC (phos-) or the PKC inhibitor staurosporine,
      prevented MARCKS phosphorylation, its release from the plasma membrane, and its
      subsequent association with lysosomes. In the presence of lysosomotropic agents
      or nocodazole, MARCKS accumulated on lysosomes and returned to the plasma
      membrane upon drug removal, further suggesting that the protein cycles between
      the plasma membrane and lysosomes. In contrast to wild-type MARCKS, the phos-
      mutant did not accumulate on lysosomes in cells treated with NH4Cl, suggesting
      that basal phosphorylation of MARCKS promotes its constitutive cycling between
      these two compartments.

PMID- 7720703
TI  - Retroviral-mediated gene transfer of the peripheral myelin protein PMP22 in
      Schwann cells: modulation of cell growth.
AB  - The peripheral myelin gene PMP22 is the rat and human homologue of the murine
      growth arrest-specific gene gas3. Besides a putative role of PMP22 in
      myelination, a regulatory function in cell growth has been suspected. Here we
      have investigated both the expression of PMP22 during cell cycle progression of
      cultured rat Schwann cells and the influence of altered levels of PMP22 on
      Schwann cell growth. When resting cells were stimulated to begin the cell cycle,
      the regulation of PMP22 mRNA resembled the growth arrest-specific pattern of gas3
      expression observed previously in NIH3T3 fibroblasts. To prove a growth
      regulatory function of PMP22, we generated Schwann cell cultures by infection
      with retroviral PMP22 expression vectors that constitutively expressed PMP22 cDNA
      sequences, in either the sense or antisense orientation. Transduced cells
      carrying the sense construct overexpressed PMP22 mRNA and protein, whereas in
      cells infected with an antisense PMP22 expression vector PMP22 mRNA levels were
      reduced markedly. Altered levels of PMP22 significantly modulated Schwann cell
      proliferation, as judged by 5-bromo-2'-deoxy-uridine incorporation into
      replicated DNA. In asynchronously dividing cultures enhanced expression of PMP22
      decreased DNA synthesis to 60% of the control level. Conversely, reduced levels
      of PMP22 mRNA led to enhanced DNA synthesis of approximately 150%. Further cell
      cycle analyses by flow cytometry revealed that overexpression of PMP22 delayed
      serum- and forskolin-stimulated entry of resting Schwann cells from G0/G1 into
      the S + G2/M phases by approximately 8 h, whereas underexpression of PMP22 mRNA
      slightly increased the proportion of cells that entered the S + G2/M
      phases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720704
TI  - Direct involvement of p53 in programmed cell death of oligodendrocytes.
AB  - A covalent dimer of interleukin (IL)-2, produced in vitro by the action of a
      nerve-derived transglutaminase, has been shown previously to be cytotoxic to
      mature rat brain oligodendrocytes. Here we report that this cytotoxic effect
      operates via programmed cell death (apoptosis) and that the p53 tumor suppressor
      gene is involved directly in the process. The apoptotic death of mature rat brain
      oligodendrocytes in culture following treatment with dimeric IL-2 was
      demonstrated by chromatin condensation and internucleosomal DNA fragmentation.
      The peak of apoptosis was observed 16-24 h after treatment, while the commitment
      to death was already observed after 3-4 h. An involvement of p53 in this process
      was indicated by the shift in location of constitutively expressed endogenous p53
      from the cytoplasm to the nucleus, as early as 15 min after exposure to dimeric
      IL-2. Moreover, infection with a recombinant retrovirus encoding a C-terminal p53
      miniprotein, shown previously to act as a dominant negative inhibitor of
      endogenous wild-type p53 activity, protected these cells from apoptosis.

PMID- 7720705
TI  - Thyroid hormone regulates stromelysin expression, protease secretion and the
      morphogenetic potential of normal polarized mammary epithelial cells.
AB  - Stromelysins are a group of proteases which degrade the extracellular matrix and
      activate other secreted proteases. Stromelysin (ST)-1 and ST-2 genes are induced
      by tumor promoters, oncogenes and growth factors, and have been involved in
      acquisition of the malignant phenotype. We show here that the thyroid hormone
      (T3) increases ST-1 and ST-2 expression in a non-transformed mouse mammary
      epithelial cell line (EpH4) in a way that is dependent on the level of thyroid
      receptor/c-erbA (TR alpha-1) expression. In agreement with this, T3 increases the
      secreted stromelysin activity and enhances the gelatinolytic activity of type IV
      collagenase. We have also demonstrated that T3 affects the epithelial polarity of
      EpH4 cells, diminishing the transepithelial electrical resistance of monolayers
      cultured on permeable filters, causing an abnormal distribution of polarization
      markers and the disruption of the organized 3-D structures formed by these cells
      in type I collagen gels. These results indicate that the ligand-activated TR
      alpha-1 plays an important role in regulating the morphogenetic and invasive
      capacities of mammary epithelial cells. Because the c-erbA locus is altered in
      several types of carcinoma, an altered or deregulated TR alpha-1 expression may
      also be important for breast cancer development and metastasis.

PMID- 7720706
TI  - Tumor necrosis factor (TNF)-alpha activates c-raf-1 kinase via the p55 TNF
      receptor engaging neutral sphingomyelinase.
AB  - TNF-alpha mediates proliferation, functional activation and apoptotic death of
      cells depending upon its concentration and target cell type. The signaling
      pathways used by TNF-alpha to mount these responses are, at present, not
      completely understood. We report here that TNF-alpha promotes dose- and time
      dependent phosphorylation and activation of the c-raf-1 kinase engaging the type
      I p55 TNF receptor (TNF-R). c-raf-kinase activation was duplicated by an
      agonistic monoclonal antibody directed against the p55 TNF-R. Moreover, ectopic
      expression of the human p55 TNF-R in murine pre-B 70Z/3 cells was sufficient to
      confer c-raf-1-kinase activation by human TNF-alpha. By inhibiting intracellular
      activation of acidic sphingomyelinase (SMase) and by using deleted forms of the
      type I TNF-R it was shown that the neutral, but not the acidic SMase,
      participated in TNF-alpha-mediated phosphorylation and activation of the c-raf
      kinase. TNF-alpha-induced transcriptional activation of a heterologous promoter
      construct harboring the AP-1 binding site was also mediated by the type I p55 TNF
      R. In this case the initiation of transcription required the same cytoplasmic
      domain as that responsible for activation of c-raf-1 kinase and was liberated in
      the presence of a dominant negative mutant of c-raf-1.

PMID- 7720707
TI  - Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5
      transduce signals through two STAT5 homologs.
AB  - Interleukin-3 (IL-3) is an important regulator of hemopoiesis and considerable
      effort has been directed towards the study of its mechanism of signal
      transduction. In this paper, we describe the first molecular identification of a
      STAT transcription factor that is activated by IL-3. STATs exist in a
      cytoplasmic, transcriptionally inactive form which, in response to extracellular
      signals, become tyrosine phosphorylated and translocate to the nucleus where they
      bind to specific DNA elements. Several of these DNA elements were found which
      bind proteins in an IL-3-responsive manner. Analysis of these bandshift complexes
      with available antibodies to the known STATs suggests that IL-3 activates the DNA
      binding ability of STAT5, a protein which was originally characterized as a
      prolactin-responsive transcription factor in sheep. IL-5 and granulocyte
      macrophage colony stimulating factor (GM-CSF), which share a common signaling
      receptor subunit with IL-3, also activate STAT5. Unexpectedly, two murine STAT5
      homologs, 96% identical to each other at the amino acid level, were isolated and
      IL-3-dependent GAS binding could be reconstituted in COS cells transfected with
      IL-3 receptor and either STAT5 cDNA. In IL-3-dependent hemopoietic cells, both
      forms of STAT5 are expressed and activated in response to IL-3.

PMID- 7720708
TI  - Inactivation of Myf-6 and Myf-5 genes in mice leads to alterations in skeletal
      muscle development.
AB  - Myf-6, alternatively called MRF4 or herculin, is a member of a group of muscle
      specific transcription factors which also comprises Myf-5, myogenin and MyoD. All
      family members show distinct expression patterns during skeletal muscle
      development and can convert a variety of cell lines to myocytes. We disrupted the
      Myf-6 gene in mice to investigate its functional role in the network of
      regulatory factors controlling myogenesis. Homozygous mice carrying the disrupted
      Myf-6 gene show pronounced down-regulation of Myf-5 transcription for reasons
      presently unknown. Consequently, these mice represent a double knock-out model
      for Myf-6 and Myf-5. The mutants resemble most of the Myf-5 phenotype with
      aberrant and delayed early myotome formation and lack of distal rib structures.
      In addition, we find a reduction in the size of axial muscles in the back. Apart
      from changes in the pattern of some contractile protein isoforms, the existing
      myofibers appear fairly normal. This suggests that Myf-6 has no major role in the
      maturation of myotubes, as previously proposed. Our results provide evidence that
      skeletal myogenesis can proceed in the absence of two myogenic factors, Myf-5 and
      Myf-6, therefore they must exert largely non-redundant functions in vivo.

PMID- 7720709
TI  - RAR-specific agonist/antagonists which dissociate transactivation and AP1
      transrepression inhibit anchorage-independent cell proliferation.
AB  - Using retinoic acid receptor (RAR) reporter cells specific for either RAR alpha,
      beta or gamma, we have identified synthetic retinoids which specifically induce
      transactivation by RAR beta, while antagonizing RA-induced transactivation by RAR
      alpha and RAR gamma. Like RA, these synthetic retinoids allow all three RAR types
      to repress AP1 (c-Jun/c-Fos) activity, demonstrating that the transactivation and
      transrepression functions of RARs can be dissociated by properly designed
      ligands. Using AP1 reporter cells, we also show that glucocorticoids or vitamin
      D3, together with either RA or these 'dissociating' synthetic retinoids, can
      synergistically repress phorbol ester-induced AP1 activity. RA, but not these
      'dissociating' retinoids, induced transcription of an interleukin-6 promoter
      based reporter gene transiently transfected into HeLa cells together with RARs.
      Using Ki-ras-transformed 3T3 cells as a model system, we show that both RA and
      the 'dissociating' retinoids inhibit anchorage-independent cell proliferation,
      suggesting that retinoid-induced growth inhibition may be related to AP1
      transrepression.

PMID- 7720710
TI  - High mobility group protein 2 functionally interacts with the POU domains of
      octamer transcription factors.
AB  - The octamer transcription factors Oct1 and Oct2 are involved in the
      transcriptional regulation of both lymphoid-specific and ubiquitously expressed
      genes. Their activity depends critically on their interaction with distinct
      cellular cofactors. Therefore, we have isolated cDNAs encoding proteins that
      physically interact with Oct2. Here we describe the analysis of one such clone,
      representing the murine homologue of high mobility group (HMG) protein 2. We have
      mapped the interaction domains for both proteins and have shown that HMG2 and
      Oct2 interact via their HMG domains and POU homeodomains, respectively. This
      interaction is not restricted to Oct2, as other members of the octamer
      transcription factor family like Oct1 and Oct6 also interact with HMG2. The
      interaction with HMG2 results in a marked increase in the sequence-specific DNA
      binding activity of the Oct proteins. Interestingly, the HMG2 protein is not
      present in the protein-DNA complex detected by an electrophoretic mobility shift
      assay. The Oct and HMG2 proteins also interact in vivo. A chimeric protein, in
      which the strong transactivation domain of VP16 was fused directly to the HMG
      domains of HMG2, stimulated the activity of an octamer-dependent reporter
      construct upon cotransfection. Furthermore, the expression of antisense RNA for
      HMG2 specifically reduces octamer-dependent transcription. These results suggest
      that one of the functions of HMG2 is to support the octamer transcription factors
      in their role as transcriptional activators.

PMID- 7720711
TI  - Transcriptional silencing by the Polycomb protein in Drosophila embryos.
AB  - Polycomb group (Pc-G) proteins act to keep homeotic genes stably and heritably
      silenced during Drosophila development. Here, it is shown that Polycomb (Pc), one
      of the Pc-G proteins, acts as a transcriptional silencer in Drosophila embryos if
      tethered to reporter genes by the DNA binding domain of GAL4 (i.e. as a GAL-Pc
      fusion protein). The results suggest that silencing by GAL-Pc requires the C
      terminal portion of Pc, but not the chromodomain. If a pulse of Gal-Pc is
      provided, synthetic reporter genes are repressed, though only transiently. In
      contrast, reporter genes containing homeotic gene sequences remain stably and
      heritably silenced in a Pc-G gene-dependent fashion, even when GAL-Pc is no
      longer present. This implies that GAL-Pc recruits Pc-G proteins to DNA and
      suggests that maintenance of silencing requires the anchoring of Pc-G proteins to
      specific cis-regulatory sequences present in homeotic genes. The extent of DNA
      over which the Pc-G machinery acts is quite selective, as silencing established
      on one enhancer does not necessarily 'spread' to a juxtaposed synthetic enhancer.

PMID- 7720712
TI  - Three protein binding sites form an enhancer that regulates sex- and fat body
      specific transcription of Drosophila yolk protein genes.
AB  - Transcription of the Drosophila yolk protein (Yp) genes is regulated by the
      somatic sex determination pathway. A gene at the bottom of this pathway,
      doublesex, encodes the female-specific DSXF and male-specific DSXM proteins that
      bind to and regulate transcription from several sites in the Yp genes. We report
      site-directed mutagenesis, protein binding and germline transformation
      experiments that identify and characterize the activity of a single binding site
      (dsxA) for the doublesex proteins and two binding sites for other regulatory
      proteins. A single copy of the three sites is sufficient to direct the sex and
      fat body specificities of Yp transcription. The sites form an enhancer with two
      strongly synergistic enhancer elements. One element (22 bp) consists of dsxA and
      an overlapping site, bzip1, that binds the DmC/EBP (slbo) protein, a member of
      the bZIP family of transcriptional activators. The other element is an 11 bp
      binding site (ref1) for an unknown protein. Tissue-specific activation requires
      strong cooperation between the ref1 site and the bzip1 or dsxA sites. Sex
      specificity is regulated exclusively by the dsxA site which connects the sex
      determination pathway to the target gene through DSXM repression and DSXF
      activation.

PMID- 7720713
TI  - AFT1: a mediator of iron regulated transcriptional control in Saccharomyces
      cerevisiae.
AB  - Using a scheme for selecting mutants of Saccharomyces cerevisiae with
      abnormalities of iron metabolism, we have identified a gene, AFT1, that mediates
      the control of iron uptake. AFT1 encodes a 78 kDa protein with a highly basic
      amino terminal domain and a glutamine-rich C-terminal domain, reminiscent of
      transcriptional activators. The protein also contains an amino terminal and a C
      terminal region with 10% His residues. A dominant mutant allele of this gene,
      termed AFT1-1up, results in high levels of ferric reductase and ferrous iron
      uptake that are not repressed by exogenous iron. The increased iron uptake is
      associated with enhanced susceptibility to iron toxicity. These effects may be
      explained by the failure of iron to repress transcription of FRE1, FRE2 and FET3.
      FRE1 and FRE2 encode plasma membrane ferric reductases, obligatory for ferric
      iron assimilation, and FET3 encodes a copper-dependent membrane-associated
      oxidase required for ferrous iron uptake. Conversely, a strain with interruption
      of the AFT1 gene manifests low ferric reductase and ferrous iron uptake and is
      susceptible to iron deprivation, because of deficient expression of FRE1 and
      negligible expression of FRE2 and FET3. Thus, AFT1 functions to activate
      transcription of target genes in response to iron deprivation and thereby plays a
      central role in iron homeostasis.

PMID- 7720714
TI  - Multimerization and transcriptional activation of the phosphoprotein (P) of
      vesicular stomatitis virus by casein kinase-II.
AB  - Casein kinase-II (CK-II) is a widely distributed protein kinase, which plays
      numerous roles in the regulation of transcription through modification of
      transacting transcription factors. Phosphorylation of vesicular stomatitis virus
      (VSV) P protein by CK-II was found to be both necessary and sufficient for
      transcriptional activation. Upon treatment of P by CK-II, activity was acquired
      faster (t1/2 = 3.7 min) than were total phosphates (t1/2 = 7.4 min).
      Stoichiometry was 2 mol phosphate/mol P, indicating activation by phosphorylation
      at either one or both of two independent sites. The sites were identified by
      substituting aspartate (D) residues at either S60 or T62, producing proteins that
      were partly active without phosphorylation, but were fully active at higher
      concentrations; CK-II added only a single phosphate group to each of these, and
      conferred full activity. P protein doubly substituted with D at S60 and T62 was
      fully active without phosphorylation, and was not a substrate for CK-II. Active P
      protein, whether CK-II treated or doubly substituted, was shown by gel filtration
      and crosslinking to exist as a discretely multimeric, probably tetrameric,
      structure. The singly substituted mutants were partly multimeric, becoming fully
      so after CK-II treatment. Phosphorylation by CK-II thus mediates the self
      association of P into the multimeric, transcriptionally active form.

PMID- 7720715
TI  - Different domains of the murine RNA polymerase I-specific termination factor mTTF
      I serve distinct functions in transcription termination.
AB  - Termination of mouse ribosomal gene transcription by RNA polymerase I (Pol I)
      requires the specific interaction of a DNA binding protein, mTTF-I, with an 18 bp
      sequence element located downstream of the rRNA coding region. Here we describe
      the molecular cloning and functional characterization of the cDNA encoding this
      transcription termination factor. Recombinant mTTF-I binds specifically to the
      murine terminator elements and terminates Pol I transcription in a reconstituted
      in vitro system. Deletion analysis has defined a modular structure of mTTF-I
      comprising a dispensable N-terminal half, a large C-terminal DNA binding region
      and an internal domain which is required for transcription termination.
      Significantly, the C-terminal region of mTTF-I reveals striking homology to the
      DNA binding domains of the proto-oncogene c-Myb and the yeast transcription
      factor Reb1p. Site-directed mutagenesis of one of the tryptophan residues that is
      conserved in the homology region of c-Myb, Reb1p and mTTF-I abolishes specific
      DNA binding, a finding which underscores the functional relevance of these
      residues in DNA-protein interactions.

PMID- 7720716
TI  - Water release associated with specific binding of gal repressor.
AB  - Water release coupled to the association of gal repressor with DNA is measured
      from the sensitivity of the binding constant to the solution osmotic pressure,
      using neutral solutes that are typically excluded from polar protein and DNA
      surfaces. Differences in water release for binding of repressor to different
      sequences are linked with differences in specificity and binding energies. With
      sucrose, the specific binding of repressor to operator sequences is accompanied
      by the release of 130 water molecules. No water release is seen for the weak, non
      specific binding of repressor to poly(dI-dC).(dI-dC). A difference in the release
      of six water molecules is seen even for the binding of gal repressor to two
      different operator sequences that differ in affinity by only a factor of two.

PMID- 7720717
TI  - HMG-D is an architecture-specific protein that preferentially binds to DNA
      containing the dinucleotide TG.
AB  - The high mobility group (HMG) protein HMG-D from Drosophila melanogaster is a
      highly abundant chromosomal protein that is closely related to the vertebrate HMG
      domain proteins HMG1 and HMG2. In general, chromosomal HMG domain proteins lack
      sequence specificity. However, using both NMR spectroscopy and standard
      biochemical techniques we show that binding of HMG-D to a single DNA site is
      sequence selective. The preferred duplex DNA binding site comprises at least 5 bp
      and contains the deformable dinucleotide TG embedded in A/T-rich sequences. The
      TG motif constitutes a common core element in the binding sites of the well
      characterized sequence-specific HMG domain proteins. We show that a conserved
      aromatic residue in helix 1 of the HMG domain may be involved in recognition of
      this core sequence. In common with other HMG domain proteins HMG-D binds
      preferentially to DNA sites that are stably bent and underwound, therefore HMG-D
      can be considered an architecture-specific protein. Finally, we show that HMG-D
      bends DNA and may confer a superhelical DNA conformation at a natural DNA binding
      site in the Drosophila fushi tarazu scaffold-associated region.

PMID- 7720718
TI  - Frequent use of the same tertiary motif by self-folding RNAs.
AB  - We have identified an 11 nucleotide RNA motif, [CCUAAG...UAUGG], that is
      extraordinarily abundant in group I and group II self-splicing introns at sites
      known, or suspected from co-variation analysis, to interact with hairpin terminal
      loops with a GNRA consensus sequence. Base substitution experiments using a
      ribozyme-substrate system derived from a group I intron reveal that this motif
      interacts preferentially with GAAA terminal loops and binds them with remarkable
      affinity, compared with other known combinations of GNRA loops and matched
      targets. A copy of the [CCUAAG...UAUGG] motif which is present in domain I of
      many group II introns is shown to interact with the GAAA terminal loop that caps
      domain V. This is the first interaction to be identified between these two
      domains, whose mutual recognition is known to be necessary and sufficient for
      group II ribozymic activity. We conclude that interaction of [CCUAAG...UAUGG]
      with GAAA loops is one of the most common solutions used by nature to solve the
      problem of compacting and bringing together RNA structural domains.

PMID- 7720719
TI  - Desmosomes and cytoskeletal architecture in epithelial differentiation: cell type
      specific plaque components and intermediate filament anchorage.
AB  - Among the diverse kinds of intercellular, plaque-bearing, cadherin-containing
      junctions, desmosomes (maculae adhaerentes) represent a major type characterized
      by the presence of specific transmembrane glycoproteins, i.e. desmosomal
      cadherins of the desmoglein and desmocollin categories, and the cytoplasmic
      plaque proteins, desmoplakin I and plakoglobin. Recent studies, however, have
      shown that the composition of desmosomes is not identical in the various normal
      and tumorous desmosome-forming tissues and cell cultures, including diverse forms
      of epithelia and carcinomas, meningothelia and meningiomas, myocardium and the
      lymph node follicle reticulum. Desmosomes can differ in their specific complement
      of desmogleins, Dsg1-3, and desmocollins, Dsc1a-3b, as well as in the additional
      presence and in their relative amounts of certain accessory plaque proteins such
      as desmoplakin II and plakophilin 1, a basic member of the larger plakoglobin
      family of proteins ("band 6 protein"). Assembly and function of desmosomes are
      effected by the interaction of the specific complement of desmosomal cadherins
      with certain cytoplasmic proteins. In particular, the cytoplasmic portions
      ("tails") of the desmosomal cadherins contain certain domains and amino acid
      sequence motifs, identified by mutagenesis and transfection assays, that are
      essential elements in desmosome formation, notably the assembly of plaque
      proteins, and in the site-specific anchorage of intermediate-sized filaments
      (IFs) of the cytoskeleton, thereby contributing to the specific intracellular as
      well as supracellular, i.e. tissue, architecture.

PMID- 7720720
TI  - Microtubules are oriented with their minus-ends directed apically before tight
      junction formation in rat Sertoli cells.
AB  - We have examined the polarity of microtubules in Sertoli cells of the
      seminiferous epithelium during testicular development to test the hypothesis that
      microtubules change their polarity during tight junction formation. Microtubules
      in a number of polarized epithelial cells, including Sertoli cells, are oriented
      with their minus-ends directed toward the apical surface of the cell. Indirect
      evidence from cultured epithelial cell models suggests that this orientation may
      be achieved during the relocation of centrioles, reorganization of microtubules,
      and repositioning of the Golgi that occurs during tight junction formation. Using
      the microtubule hook decoration technique, we have determined the polarity of
      Sertoli cell microtubules at 5 and 15 days postnatally, prior to the
      establishment of the tight junctional complex of the blood testis barrier at 19
      days. Our results indicate that, although centrioles and the Golgi apparatus
      migrate from an infranuclear location at 5 days to a supranuclear location by 15
      days, the minus-ends of microtubules are already directed toward the apical
      surface of the cell by 5 days of age. These data indicate that the establishment
      of the apically directed minus-end orientation of microtubules of mature Sertoli
      cells precedes rearrangement of the centrioles and Golgi and is not temporally
      related to the formation of the tight junctional complex of the blood testis
      barrier.

PMID- 7720721
TI  - Fate of a fluorescent inhibitor of endopeptidase-24.11 using enzyme-expressing
      MDCK cells. Modification of its cellular processing with a monoclonal antibody.
AB  - Neutral endopeptidase-24.11 (NEP) is a membrane-bound zinc metallopeptidase which
      cleaves biologically active peptides such as the enkephalins and atrial
      natriuretic peptide. Using the specific and fluorescent thiol inhibitor of the
      enzyme, N-[fluoresceinyl]-N'-[1-(6-(3-mercapto-2-benzyl-1-oxopropyl)-amino-1-
      hexyl]-thiocarbamide (FTI), the fate of the inhibitor-enzyme complex was
      investigated by videomicrofluorimetry using MDCK epithelial cells expressing the
      rabbit peptidase thanks to a retroviral expression vector. N-[3-(R,S)
      [(hydroxyamino) carbonyl]-2-benzyl-1-oxopropyl]- glycine (HACBOGly) and the
      corresponding tritiated molecule were also used to measure the cellular pathway
      of inhibitor-NEP complexes. In the present paper, we demonstrate that, for short
      incubation times, the fluorescent probe preferentially labeled brush border
      membranes of the apical side of the MDCK cells. After more than 1 h incubation, a
      honeycomb pattern of fluorescence was observed in videomicrofluorimetry
      suggesting that part of the inhibitor was bound or localized close to the
      basolateral plasma membrane. Confocal experiments confirmed the transcytosis of
      FTI/NEP complex, from the apical to the basolateral domain. Using [3H]HACBOGly on
      filter-grown cells, after 2 and 4 h incubation at 37 degrees C, the percentage of
      basolateral membrane-bound molecules was estimated to be about 12 and 23%,
      respectively. The coincubation of the cells with FTI and 2B12, a monoclonal
      antibody raised against the rabbit enzyme, greatly modified the fluorescence
      pattern. A patchy fluorescence was observed for short incubation times,
      corresponding to cluster formation induced by antigen-antibody binding. For
      longer incubation times (> 1 h), in addition to the basolateral labeling, some
      intracellular fluorescent vesicles were observed essentially localized in the
      vicinity of the nucleus. The colocalization of FTI with Texas Red isothiocyanate
      labeled Concanavalin A (TRITC-Con A) strongly suggests an endosomal/lysosomal
      internalization pathway when FTI was incubated in the presence of 2B12 mAb.

PMID- 7720722
TI  - Conservative amino acid substitutions of the C-terminal tripeptide (Ala-Arg-Met)
      on cottonseed isocitrate lyase preserve import in vivo into mammalian cell
      peroxisomes.
AB  - The purpose of this research was twofold, a) to directly demonstrate import in
      vivo of a native plant peroxisomal protein into peroxisomes of transiently
      transfected mammalian cells, and b) to identify the targeting signal and amino
      acid substitutions thereof which preserve translocation of this plant protein
      into these peroxisomes. The protein selected for study was cottonseed isocitrate
      lyase (ICL), a glyoxylate cycle enzyme which participates in storage oil
      mobilization in oilseed cotyledons. Cultured mammalian cells were selected as the
      import system because of previous success by others with transient transfections
      and import of heterologous (not plant, however) proteins, and because neither a
      plant in vitro or transient in vivo import system was established. Optimized
      transient transfections of cultured CV-1 monkey kidney, mouse L, HeLa, and CHO
      cells resulted in punctate, anticottonseed-ICL-dependent immunofluorescent
      patterns. Colocalization in a CVH Px110 cell line of ICL with either endogenous
      catalase or with stably expressed CAT-PMP20/AKL (chloramphenicol
      acetyltransferase with a C-terminal-appended 12 amino acids ending with Ala-Lys
      Leu) demonstrated targeting of ICL to peroxisomes. Direct evidence for
      translocation of ICL into CHO cell peroxisomes was obtained from digitonin
      permeabilization experiments. The necessity of the C-terminal tetrapeptide, KARM
      COOH, was demonstrated in CHO and CV-1 cells when removal of this tetrapetide
      (leaving ICL-VVA-COOH) abolished import into peroxisomes. This result is in
      general agreement with Olsen et al. (The Plant Cell 5, 941-952 (1993)) who
      demonstrated that the 37 C-terminal amino acids of oilseed rape ICL were
      necessary for import in vivo in transgenic plants. The findings of Behari and
      Baker (J. Biol. Chem. 268, 7315-7322 (1993)), however, indicate that the C
      terminal portion of castor bean ICL is dispensible for import in vitro. Single or
      multiple conservative amino acid substitutions at each position of the C-terminal
      tripeptide of native cottonseed ICL (S for A, K for R, L for M, SK for AR, SKL
      for ARM) preserved import of the enzyme in vivo into CHO cell peroxisomes. The
      demonstrated targeting and translocation of plant ICL and C-terminal
      modifications thereof into mammalian cell peroxisomes provide important
      additional evidence for evolutionary conservation of peroxisome import machinery,
      especially relative to the PTS1 sequence.

PMID- 7720723
TI  - Identification and immunochemical characterization of a family of peroxisome
      membrane proteins (PMPs) in oilseed glyoxysomes.
AB  - Prior to this study the only antibodies available for characterizing peroxisome
      membrane proteins (PMPs) in plants were the antibodies raised against membranes
      isolated from castor bean endosperm glyoxysomes by Halpin et al. (Planta 179, 331
      339 (1989)). We raised antibodies to four different nondenatured PMP complexes
      solubilized in 0.63 M aminocaproate/1% dodecylmaltoside from alkaline carbonate
      washed, cucumber cotyledon glyoxysome membranes. The four complexes,
      approximately 290/270, 148, 128 and 67 kDa, were excised from 5 to 10%
      nondenaturing gradient gels, passively eluted from their homogenized gel slice,
      concentrated, then injected subcutaneously into rabbits. SDS-PAGE (10-15%
      gradient) of the total detergent-solubilized PMPs revealed six prominent membrane
      polypeptides: 73, 61, 52, 36, 30, and 22 kDa. The SDS-PMP composition of each
      nondenatured antigen was: PMP290/270-52, 30, 28 kDa; PMP148-30, 28, 26, 23, 22
      kDa; PMP 128-73, 66, 36, 30, 23 kDa; PMP67-34, 30 kDa. These data indicated that
      several prominent as well as several minor polypeptides were common components of
      the PMP complexes. Three of the four antisera to the complexes were polyspecific,
      recognizing several of these common SDS polypeptides, whereas the fourth
      antiserum, anti-PMP67, was monospecific for PMP30. Cross-reactivities were
      evident with each antiserum to several of these SDS PMPs from castor bean, cotton
      and sunflower. Affinity-purified anti-PMP30 and anti-PMP73 antibodies
      specifically bound to the boundary membrane of cucumber glyoxysomes in cells
      examined by indirect, postembedment (LR White), immunocytochemistry. These, and
      the family of other antibodies produced in this study, provide specific molecular
      probes essential for elucidating biogenesis and discovering function(s) of the
      integral membrane proteins in oilseed glyoxysomes.

PMID- 7720724
TI  - Immunocytochemical characterization of nuclear ribonucleoprotein fibrils in cells
      of the central nervous system of the rat.
AB  - Nucleoplasmic structural constituents observed in partially decondensed nuclei of
      the central nervous system of the rat were analyzed by postembedding
      immunoelectron microscopy using antibodies specifically recognizing heterogenous
      nuclear ribonucleoprotein (hnRNP) and small nuclear ribonucleoprotein (snRNP)
      complexes and DNA. Fibrogranular RNP structures (polyparticles) were found in
      close proximity to DNA containing fibrillar areas resulting from partial
      dispersion of compact chromatin. The polyparticle-type fibrils are labeled by
      antibodies recognizing hnRNP core proteins as well as snRNPs (Sm antigen or 70
      kDa protein of U1snRNP) or the m3G-cap structure of snRNAs. These observations
      suggest that such polyparticle-type fibrils correspond to extended perichromatin
      fibrils. Partially decondensed perichromatin granules are rarely labeled by anti
      snRNP or snRNA antibodies. When labeling occurs it is restricted to the periphery
      of the granules. However, anti-hnRNP antibodies frequently label these granules.
      Our results favor the idea, previously proposed for Balbiani ring granules, that
      perichromatin granules are formed by the folding of hnRNP containing
      perichromatin fibrils (polyparticles) in the process of splicing, and that mature
      perichromatin granules contain already spliced messenger RNA.

PMID- 7720725
TI  - Cytosolic factors block antibody binding to the C-terminal cytoplasmic tail of
      the KDEL receptor.
AB  - The mammalian KDEL receptor is an extremely hydrophobic membrane protein. One of
      the longest stretches of hydrophilic sequence resides at the C-terminus. Various
      antibodies against a synthetic peptide corresponding to this region confirmed
      that the C-terminus is exposed to the cytoplasm. It was observed that antibody
      binding to the C-terminus of the KDEL receptor was diminished during
      immunofluorescence microscopy procedures which involved fixation prior to
      permeabilization as compared to when cells were permeabilized before fixation.
      Binding of both polyclonal and monoclonal antibodies, as assessed by indirect
      immunofluorescence microscopy in digitonin permeabilized cells, was inhibited by
      preincubation with rat liver cytosol. This inhibition was not observed with
      antibody against another membrane protein (p28) with a cytoplasmically exposed
      epitope also residing in the Golgi/intermediate compartment. Rabbit reticulocyte
      lysate had a similar effect while Schizosaccharomyces pombe cytosol inhibited
      binding to a greater degree than Saccharomyces cerevisiae cytosol. This
      inhibition by cytosol was prevented by coincubation with the antibody and was
      dose-dependent on the cytosol. Inhibition did not occur on ice or at 15 degrees
      C, or when the cytosol was energy-depleted by apyrase treatment. Interestingly,
      pretreatment of permeabilized cells with N-ethylmaleimide or its addition into
      the incubation mixture abolished inhibition. N-ethylmaleimide-treated cytosol,
      however, remained inhibitory. The findings suggest the existence of cytosolic
      factor (s) which interacts specifically with the cytoplasmic C-terminus of the
      KDEL receptor, which are likely to be components of the KDEL protein retrieval
      machinery.

PMID- 7720726
TI  - Yeast Vps45p is a Sec1p-like protein required for the consumption of vacuole
      targeted, post-Golgi transport vesicles.
AB  - Over 45 VPS genes (vacuolar protein sorting) in Saccharomyces cerevisiae are
      necessary for the correct sorting and delivery of vacuolar hydrolases. Yeast
      strains carrying mutations in a subset of these VPS genes (class D vps mutants)
      are also defective in the segregation of vacuolar material into the developing
      daughter cell and are morphologically characterized by having large central
      vacuoles. The class D VPS gene products, which include a Rab5 homologue
      (VPS21/YPT51) and a syntaxin homologue (PEP12/VPS6), have been proposed to
      function together at a particular step along the vacuolar protein sorting
      pathway. We have cloned another class D VPS gene, VPS45, which is homologous to a
      growing family of genes that encode Sec1p-like proteins. Vps45p is predicted to
      be a hydrophilic protein of 577 amino acids with a molecular mass of 67 kDa.
      Fractionation studies show that Vps45p is a peripheral membrane protein that
      cofractionates with Golgi-like membranes, consistent with Vps45p functioning in
      membrane traffic between the Golgi and the vacuole. Using a temperature-sensitive
      allele of VPS45, we show that inactivation of Vps45p causes the rapid
      accumulation of small (40-60 nm) vesicles and secretion of the vacuolar hydrolase
      carboxypeptidase Y. Because the entire yeast secretory pathway is functional
      after the temperature-induced inactivation of Vps45p, we conclude that the
      accumulated vesicles represent transport intermediates between the Golgi and the
      vacuole.

PMID- 7720727
TI  - Localization of Rab5 to synaptic vesicles identifies endosomal intermediate in
      synaptic vesicle recycling pathway.
AB  - After exocytosis, synaptic vesicles rapidly endocytose and recycle but little is
      known about the molecular mechanisms involved. Rab5 is a ubiquitous low molecular
      weight GTP-binding protein required for endosomal fusion in fibroblasts. We have
      now raised polyclonal and monoclonal antibodies to rat Rab5 and show that in rat
      brain, Rab5 is a major synaptic vesicle protein. Immunoisolation of vesicular
      organelles from brain with antibodies to either Rab3A and Rab5 as small GTP
      binding proteins or with synaptophysin as general synaptic vesicle marker
      demonstrates that there are overlapping populations of synaptic vesicles
      containing either Rab5 or Rab3A or both, suggesting a stage-specific association
      of these low-molecular weight GTP-binding proteins with synaptic vesicles. Our
      data provide the first biochemical evidence that synaptic vesicle recycling
      involves an endosomal intermediate similar to that of the receptor-mediated
      endocytosis pathway.

PMID- 7720728
TI  - Subcellular localization and supramolecular organization of neuroendocrine
      specific protein B (NSP-B) in small cell lung cancer.
AB  - We have recently isolated and characterized a novel gene that is expressed in a
      neuroendocrine-specific fashion and was therefore designated neuroendocrine
      specific protein (NSP)-gene. The NSP-gene encodes three transcripts of different
      size, with unique 5'-sequences and completely overlapping 3'-sequences. The
      resulting proteins have an apparent molecular mass of 135 kDa as determined for
      NSP-A and 23 kDa as found for NSP-C. In the present study we focused on the
      biochemical characterization and subcellular localization of NSP-B, so far only
      found to be expressed in the neuroendocrine lung cancer cell line NCI-H82, and
      its relation to NSP-A. Transfection studies with the NSP-B transcript in COS-1
      cells, followed by immunoprecipitation, resulted in a set of proteins ranging in
      molecular mass from 35 to 45 kDa, identical to NSP-Bs detected by immunoblotting
      in NCI-H82. In this cell line a major NSP-B triplet in the 43 to 45 kDa range and
      a 35 kDa NSP-B were consistently detected. Only the 45 kDa NSP-B was found to be
      phosphorylated. The observed pI values of the 43 to 45 kDa triplet ranged from
      4.8 to 5.0, while the 35 kDa NSP-B has a more basic pI value of 5.7. Gel
      filtration studies show that NSP-A and NSP-B form supramolecular aggregates with
      a molecular mass of over 500 kDa, present to a minor extent in the phosphate
      buffered saline soluble cell fraction, but mainly occurring in the membranous
      pellet fraction from which they can be solubilized by Triton X-100.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7720729
TI  - cDNA cloning and characterization of a novel 16 kDa protein located in zymogen
      granules of rat pancreas and goblet cells of the gut.
AB  - By immunoscreening of a cDNA expression library of rat pancreas with a
      polyspecific antibody to purified rat zymogen granule membranes, we have cloned a
      cDNA coding for a novel protein of about 16 kDa (ZG-16p). By both
      immunocytochemistry and Western blot analysis of different fractions of rat
      pancreas with anti-ZG-16 antibodies, the protein could be localized in the
      content fraction of zymogen granules and also, to a lesser extent, bound to the
      granule membranes. Computer-based sequence analysis revealed no significant
      homologies to any of the known proteins of zymogen granules. A N-terminal portion
      of about 20 amino acids was predicted as a potential secretory signal sequence
      and may reflect the intracellular localization of the protein. As revealed by
      Northern blot analysis of total RNA from various organs of the rat, expression of
      the corresponding gene is restricted by only pancreas, colon, duodenum, and, to a
      much lesser extent, stomach. No traces of ZG-16 RNA were detectable in any of the
      other tissues tested so far. Expression of the ZG-16-gene in pancreatic cells is
      slightly stimulated by treatment of rats with cerulein, a decapeptide analogue of
      cholecystokinin, which is known to stimulate secretion in acinar cells. In
      contrast, treatment of the rat pancreatic tumor cell line, AR4-2J, with 10 nM
      dexamethasone, which has been shown to increase the synthesis and secretion of
      all secretory enzymes of rat pancreas accompanied with an increase in the
      secretory machinery, leads to a remarkable increase in the expression of ZG-16.
      Thus the expression pattern of the ZG-16 gene in response to hormonal stimulation
      of rat pancreatic acinar cells resembles those found for most of the secretory
      enzymes. The localization of ZG-16p and the regulation of ZG-16 gene expression
      in response to hormonal stimulation of pancreatic acinar cells leads us to
      presume that this novel protein has a functional role in the complex and ill
      understood processes involved in the regulated secretory pathway of these cells.

PMID- 7720730
TI  - Trophic effect of insulin-like growth factor-I on metanephric development:
      relationship to proteoglycans.
AB  - Many hormones/factors influence the total body growth and development during
      embryonic life, and very few studies have been carried out to ascertain their
      effects on the individual organ system. In this study, the effect of exogenous
      insulin-like growth factor-I (IGF-I) on embryonic kidneys was investigated, and
      correlated with phenotypic and gene expression and synthesis of extracellular
      matrix (ECM) proteoglycans (PGs). Antisense experiments were carried out to
      elucidate the role of endogenous (IGF-I in metanephric development. Mouse
      metanephroi, harvested at 13th day of gestation, were exposed to IGF-I (100
      ng/ml) in an organ culture for 7 days. An enlargement of the metanephroi with
      accentuation of its lobules, and increase in the nephron population and
      [3H]thymidine incorporation was observed. Immunofluorescence studies and Southern
      blot analysis of polymerase chain reaction products indicated augmented
      expression of the ECM PGs. A heavy concentration of [35S]sulfate-associated
      radioactivity over the tips of ureteric bud branches and ECM components of
      maturing glomeruli was seen. Maximal effect of radioincorporation was observed on
      day-4 of the culture, the period when the concentration of endogenous IGF-I is
      the highest. PGs synthesized had elevated proportions of chondroitin sulfate vs
      heparan sulfate and of free chains, and reduced charge-density characteristics.
      Immunoprecipitation studies of [35S]methionine-labeled glycoproteins revealed an
      increased synthesis of core-peptide of the PGs. IGF-I antisense oligonucleotide
      caused retardation in the growth of the kidneys along with the decrease in de
      novo synthesis of PGs. These findings indicate that IGF-I, a polypeptide
      essential to the renal growth and development, has a trophic effect on the
      embryonic kidney during the postinductive period of metanephric development, and
      the observed response has a temporal relationship with the increased synthesis of
      the PGs.

PMID- 7720731
TI  - Immunological properties and tissue localization of two different collagen types
      in annelid and vestimentifera species.
AB  - Rabbit antisera against cuticle and interstitial collagens from shallow sea water
      and hydrothermal vent annelids (Arenicola marina, and the pompeii worm Alvinella
      pompejana) and the vestimentiferan tube worm Riftia pachyptila showed a clear
      distinction between the two types of collagens, a broad cross-reactivity among
      the worm collagens and no reactions with various mammalian collagens. The
      antibodies reacted with various epitopes found on both triple helical and
      unfolded collagens. The cuticle collagens were localized by immunofluorescence to
      the outer surface of the epidermis and in annelids additionally to the anterior
      part of the digestive tract. The interstitial collagen was detected underneath
      the epidermis and between distinct muscle layers. Both collagens were also
      detected in the anterior obturaculum, a tissue unique to vestimentifera. They
      were located either in the periphery of the tissue (cuticle collagen) or in the
      central part (interstitial collagen), which appeared to be a large extracellular
      matrix. Both collagens, however, showed a different supramolecular organization
      in the obturaculum when compared to the posterior body wall collagens. The
      identity of the interstitial collagens from the two locations was verified by
      biochemical analysis. These data demonstrate a very special and rigid matrix
      structure in the obturaculum, which may adapt it to specific physiological
      functions.

PMID- 7720732
TI  - Characterization of human TUR leukemia cells: continued cell cycle progression in
      the presence of phorbol ester is associated with resistance to apoptosis.
AB  - Human TUR leukemia cells were generated as a subclone of U937 monoblastoid
      leukemia cells. There was no obvious difference in the ultrastructure of both
      cell lines. Like in U937 cells, the expression of monocyte-specific surface
      markers such as CD14 was negligible in TUR cells. U937 cells and other human
      myeloid leukemia cell lines (HL-60, THP-1) can be induced by the phorbol ester 12
      O-tetradecanoylphorbol-13-acetate (TPA) to differentiate along the monocytic
      pathway. In contrast, exposure to TPA had no effect on the induction of the
      differentiation program in TUR cells. Thus, the presence of leukocyte integrins
      including CD11 and CD18, which are significantly induced during TPA-induced
      differentiation of HL-60, U937 and THP-1 cells, remained nearly unchanged at low
      levels in both TUR and TPA-treated TUR cells. Furthermore, while expression of
      major histocompatibility complex (MHC) class II antigens on U937 and TPA-treated
      U937 cells is barely detectable, there was a significantly constitutive
      expression of MHC class II, particularly human lymphocyte antigen (HLA-DR) on the
      surface of TUR and TPA-treated TUR cells. Exposure of human myeloid leukemia
      cells to TPA is also associated with growth arrest resulting either in a
      retrodifferentiation process or in programmed cell death. In contrast, TUR cells
      continued to proliferate in the presence of TPA although the proliferative
      capacity was continuously reduced by increasing concentrations of TPA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7720733
TI  - Immunochemical identification of insect hemocyte populations: monoclonal
      antibodies distinguish four major hemocyte types in manduca sexta.
AB  - We have made 140 monoclonal antibodies to hemocytes (insect blood cells) from
      Manduca sexta. Four of these antibodies, when used in immunofluorescent
      microscopy of fixed hemocytes, distinguish the four main morphologically distinct
      hemocyte types. Plasmatocytes, granular cells, and oenocytoids are each
      recognized by a unique antibody specific to that type; spherulocytes are
      recognized by an antibody that also binds to plasmatocytes. When used in flow
      cytometry with nonfixed hemocytes, three of the four antibodies bind their
      respective cells; the oenocytoid marker failed to bind to any hemocytes. This set
      of four monoclonal antibodies may be useful for labeling individual cell types
      and for separating the different hemocyte types for further study of hemocyte
      functions.

PMID- 7720734
TI  - Epidermal naevus syndrome associated with polyostotic fibrous dysplasia and
      central precocious puberty.

PMID- 7720735
TI  - Anticardiolipin antibodies in children and adolescents with insulin-dependent
      diabetes mellitus.
AB  - Anticardiolipin antibodies were determined in 29 diabetic children and
      adolescents, aged 3.9-26.8 years, with disease duration from 1 month to 19 years.
      Anti-islet cell antibodies (ICA-IgG and CF-ICA), anti-insulin antibodies (IAA),
      antithyroid antibodies and non organ-specific (NOSA) antibodies were also
      determined. Patients were grouped according to insulin-dependent diabetes
      mellitus (IDDM) duration: group I (n = 11) < 6 months, and group II (n = 18) > 5
      years. Eleven of group II patients showed precocious signs of micro-angiopathic
      complications. Forty-two age- and sex-matched healthy subjects served as
      controls. IgG and IgM anticardiolipin antibodies were evaluated by ELISA and
      their results expressed as arbitrary units (AU). IgG anticardiolipin antibodies
      were found in 7 patients (24%), while IgM anticardiolipin antibodies were absent
      in all. IgG anticardiolipin antibodies were more frequent in IDDM patients than
      in controls (P < 0.005) and group I (in 6 out of 11 patients; 54.5%) than in
      group II (in 1 out of 18 patients; 5.5%) (P < 0.025). In five out of six group I
      patients with IgG anticardiolipin antibodies, ICA-IgG and/or CF-ICA were also
      found. No correlation was observed between anticardiolipin and other auto
      antibodies, micro-angiopathic complications, and HLA typing. CONCLUSION:
      Anticardiolipin antibodies may reflect an abnormal immunological response in the
      early stage of diabetes mellitus and represent a transient auto-immune
      phenomenon.

PMID- 7720736
TI  - Growth retardation and reduced growth hormone secretion in a boy with achalasia.
AB  - A 15-year-old boy with achalasia of the oesophagus is described in whom growth
      retardation was the presenting and misleading symptom. Growth hormone (GH) and
      insulin-like growth factor-I secretion were decreased but GH therapy was
      unsuccessful. After pneumatic dilatation of the oesophageal sphincter catch up
      growth occurred. CONCLUSION: In children with inconclusive results of GH
      stimulation tests and unresponsiveness to GH treatment, rare causes of growth
      retardation due to malnutrition or malabsorption should be considered.

PMID- 7720737
TI  - Reversible hepatic veno-occlusive disease in an infant after consumption of
      pyrrolizidine-containing herbal tea.
AB  - Veno-occlusive disease was diagnosed in an 18-month-old boy who had regularly
      consumed a herbal tea mixture since the 3rd month of life. The boy developed
      portal hypertension with severe ascites. Histology of the liver showed
      centrilobular sinusoidal congestion with perivenular bleeding and parenchymal
      necrosis without cirrhosis. The tea contained peppermint and what the mother
      thought was coltsfoot (Tussilago farfara). The parents believed the tea aided the
      healthy development of their child. Pharmacological analysis of the tea compounds
      revealed high amounts of pyrrolizidine alkaloids. Seneciphylline and the
      corresponding N-oxide were identified as the major components by thin-layer
      chromatography, mass spectrometry and NMR spectroscopy. We calculated that the
      child had consumed at least 60 micrograms/kg body weight per day of the toxic
      pyrrolizidine alkaloid mixture over 15 months. Macroscopic and microscopic
      analysis of the leaf material indicated that Adenostyles alliariae (Alpendost)
      had been erroneously gathered by the parents in place of coltsfoot. The two
      plants can easily be confused especially after the flowering period. The child
      was given conservative treatment only and recovered completely within 2 months.
      CONCLUSION: In all cases of veno-occlusive disease pyrrolizidine alkaloids
      ingestion should be excluded. The identity of collected plant material should be
      verified by pharmaceutically trained experts and information of composition,
      dosage and mode of administration should be included in guidelines for herbal
      preparations.

PMID- 7720738
TI  - Perirenal mass of Langerhans cell histiocytosis.
AB  - A 15-month-old girl with Langerhans cell histiocytosis (LCH), Letterer-Siwe
      disease, was referred to our hospital in 1984. Whilst on treatment with cytotoxic
      drugs, a perirenal mass was detected and hydronephrosis became evident when she
      was 29 months old. Percutaneous nephrostomy tubes were placed in the pelvis,
      bilaterally and replaced every 6 months. The mass was not completely controlled
      and chronic pyelonephritis continued. Biopsy of the mass convoluted kidney hilus
      revealed histiocytic invasion. Although multiple organ systems are involved in
      LCH and abdominal malignant tumours may be accompanied by hydronephrosis, to our
      knowledge, this is the first case report of abdominal LCH and the ensuing
      hydronephrosis. Percutaneous nephrostomy tubes proved useful, but more
      convenient, less painful and infection-limited approaches need to be designed.

PMID- 7720739
TI  - Neurobrucellosis in children.
AB  - Neurobrucellosis is an uncommon disease in children. The authors present two
      cases of brucellar meningo-encephalitis. Headache and vomiting were the main
      complaints and one child had also some behavioural disturbance as well as
      papilloedema and sixth cranial nerve palsy. The clinical diagnosis was suggested
      by epidemiological data in both cases. Blood and CSF cultures confirmed brucellar
      aetiology in one of the cases and positive serum and CSF specific antibodies in
      both. Clinical course was favourable after treatment with doxycycline, rifampicin
      and streptomycin. No relapse occurred and there were no sequelae. CONCLUSION:
      Neurobrucellosis should be considered in the differential diagnosis of
      neurobehavioural disturbance of children living in areas where brucellosis is
      endemic.

PMID- 7720741
TI  - The Antley-Bixler syndrome: report of two familial cases with severe renal and
      anal anomalies.
AB  - The Antley-Bixler syndrome is characterized by premature closure of coronal and
      lambdoidal sutures, proptosis, depression of the nasal bridge, brachycephaly,
      radio-humeral synostosis and bowing of ulnae and femora associated with
      fractures. Most cases have been reported after birth with only one case diagnosed
      prenatally after recurrence of this autosomal recessive syndrome. The two present
      cases are of interest because of prenatal diagnosis of renal agenesis in the
      first case and early detection of clinical signs during the second pregnancy.
      Beside the unusual severity of the renal abnormalities, both cases had an
      imperforate anus in addition to the more common genital abnormalities.
      CONCLUSION: Renal agenesis and imperforate anus may occur in the Antley-Bixler
      syndrome.

PMID- 7720740
TI  - Genetic counselling on brittle grounds: recurring osteogenesis imperfecta due to
      parental mosaicism for a dominant mutation.
AB  - Osteogenesis imperfecta (OI), a dominantly inherited connective tissue disorder,
      is usually caused by defects in collagen I. There is growing evidence for
      parental mosaicism that results in affected children born to unaffected parents.
      This situation poses a difficult task for the geneticist because a mosaic parent
      may appear clinically healthy while carrying the mutation in a fraction of her or
      his gonadal cells. To illustrate this problem, we report a Swiss couple whose
      first child was affected with severe OI. The unexpected recurrence of the
      disorder in the second child raised the suspicion of a recessive trait or,
      rather, of parental mosaicism. We identified the responsible collagen mutation in
      the COL1A2 gene (Gly688Ser in the alpha 2(I)-chain) in both children and
      demonstrated the father to be a somatic mosaic for this mutation and to have
      subtle clinical signs such as soft skin and short stature that may be a result of
      his mosaic state. CONCLUSION: After the birth of a child affected with OI the
      possibility of parental mosaicism should be considered and options for prenatal
      diagnosis discussed.

PMID- 7720742
TI  - Hemimegalencephaly, hemihypertrophy and vascular lesions.
AB  - We report on two children with hemihypertrophy and ipsilateral
      hemimegalencephaly. Vascular lesions in one were consistent with a diagnosis of
      the Klippel-Trenaunay-Weber Syndrome. MRI performed in the first days of life and
      at 1 month of age revealed the presence of the neuronal anomaly. CONCLUSION: The
      occurrence of hemimegalencephaly in our patients indicates that hemihypertrophy
      and vascular dysplasia are pathogenetically related phenomena of a continuous
      spectrum in which this brain disorder may appear.

PMID- 7720743
TI  - Comparison of C-reactive protein and white blood cell count with differential in
      neonates at risk for septicaemia.
AB  - We prospectively compared the diagnostic value of C-reactive protein (CRP) and
      white blood cell counts for detection of neonatal septicaemia. Sensitivity and
      specifity in receiver operating characteristics, and positive and negative
      predictive value of CRP and white blood cell count were compared in 195
      critically ill preterm and term newborns clinically suspected of infection. Blood
      cultures were positive in 33 cases. During the first 3 days after birth CRP
      elevation (sensitivity 75%, specifity 86%), leukopenia (67%/90%), neutropenia
      (78%/80%) and immature to total neutrophil count (I/T) ratio (78%/73%) were good
      diagnostic parameters, as opposed to band forms with absolute count (84%/66%) or
      percentage (79%/71%), thrombocytopenia (65%/57%) and toxic granulations
      (44%/94%). Beyond 3 days of age elevated CRP (88%/87%) was the best parameter.
      Increased total (84%/66%) or percentage band count (79%/71%) were also useful.
      Leukocytosis (74%/56%), increased neutrophils (67%/65%), I/T ratio (79%/47%),
      thrombocytopenia (65%/57%) and toxic granulations had a low specifity. The
      positive predictive value of CRP was 32% before and 37% after 3 days of age, that
      of leukopenia was 37% in the first 3 days. CONCLUSION: During the first 3 days of
      life CRP, leukopenia and neutropenia were comparably good tests while after 3
      days of life CRP was the best single test in early detection of neonatal
      septicaemia. Serial CRP estimations confirm the diagnosis, monitor the course of
      infection and the efficacy of antibiotic treatment.

PMID- 7720744
TI  - Percutaneous central venous catheter use in the very low birth weight neonate.
AB  - A retrospective study was carried out comparing 61 very low birth weight infants
      (VLBW) with percutaneous central venous catheters with 92 infants managed with
      peripheral cannulae. Eighteen infants developed one or more episodes of catheter
      associated bacteraemia. In 70% of cases the infection was successfully treated
      with the line in situ. Logistic regression analysis was performed to examine risk
      factors for bacteraemia. The duration of intravenous fluids and of intermittent
      positive pressure ventilation were both significant risks for infection (odds
      ratios and 95% confidence limits 4.4, 2.7-12.0 and 2.5, 1.0-6.1 respectively),
      but the presence of a silastic catheter was not an independent risk factor (odds
      ratio 0.6, 95% confidence limits 0.1-3.0). CONCLUSION: Percutaneous central
      venous catheters provide a satisfactory means of delivering parenteral nutrition
      with minimal disturbance to ill VLBW infants.

PMID- 7720745
TI  - Neonatal hypertension and cardiac failure.
AB  - Two newborn infants developed cardiac failure due to severe hypertension which
      was recognised as the heart failure was treated. Renal abnormalities were found
      in both infants who are normotensive off treatment at 18 months follow up. The
      finding of hypertension rather than hypotension in the presence of cardiac
      failure and the apparent absence of a cardiac abnormality should prompt a search
      for a renal or renovascular cause.

PMID- 7720746
TI  - Neurological 'soft' signs may identify children with sickle cell disease who are
      at risk for stroke.
AB  - Stroke is one of the most frequent complications of sickle cell disease (HbSS),
      occurring in 7-17% of children. Recent studies recognized more minor lesions on
      MRI, not associated with clinical signs on standard neurological examination,
      which however have been found to be a risk factor for developing stroke later.
      The aim of this study was to evaluate whether minor lesions observed on imaging
      could be associated with 'soft' neurological signs not detectable on conventional
      neurological examination. Fourteen children with HbSS were assessed with MRI,
      standard neurological examination and evaluation of 'soft' signs (Zurich
      Neuromotor Test) and motor function (Movement ABC). Eight of the 14 children
      scanned showed lesions on MRI but only 3 of the full cohort were abnormal on
      standard neurological examination. However, all of the eight children with MRI
      lesions also showed abnormal signs on at least one of the two tests (Zurich and
      Movement ABC). All the children with normal MRI were normal on all the tests
      performed. The sensitivity of Zurich Neuromotor Test and Movement ABC in the
      group of children with MRI lesions is 0.88 and 0.75, respectively, and increases
      to 1 when the two tests are used together. The specificity of both tests is 1
      even when the tests are used separately. CONCLUSION: Although the number of cases
      is small, 'soft' signs may reliably identify the presence of even minor MRI
      lesions, allow the evaluation of the global incidence of major and minor
      neurological signs and may also help to identify the population at risk for
      developing strokes. This population could then be closely monitored and benefit
      from early intervention.

PMID- 7720747
TI  - Specific decrease of anti-pseudomonal IgA after anti-pseudomonal therapy in
      cystic fibrosis.
AB  - In patients with cystic fibrosis (CF) and chronic colonisation with Pseudomonas
      aeruginosa, specific anti-pseudomonal IgG and IgA, as well as serum
      immunoreactive protein C, WBC and differential count, ESR, pulmonary function and
      chest radiograph score were determined before and after a 2 week intravenous
      course of anti-pseudomonal antibiotics in 32 cases of acute exacerbation of
      pulmonary infection. Specific anti-pseudomonal IgA but not specific anti
      pseudomonal IgG decreased significantly after treatment. Log of anti-pseudomonal
      IgA but not log anti-pseudomonal IgG correlated well with disease severity as
      assessed by the Brasfield chest radiograph score (r 0.57), forced expiratory
      volume in 1 s (r 0.6) as well as C-reactive protein (r 0.62). CONCLUSION:
      Specific anti-pseudomonal IgA may be a better parameter than specific IgG in the
      follow up of lung infection in patients with CF, probably because it more closely
      reflects ongoing endobronchial infection, the major pathology in CF lungs.

PMID- 7720748
TI  - Failure to detect phenylketonuria.

PMID- 7720749
TI  - Neonatal aortic thrombosis mimicking coarctation of the aorta.

PMID- 7720750
TI  - Inotropes in preterm infants.

PMID- 7720751
TI  - Intrathecal rubella antibodies in an adolescent with Guillain-Barre syndrome
      after mumps-measles-rubella vaccination.

PMID- 7720752
TI  - Is the medium-chain acyl-CoA dehydrogenase G985 mutation involved in sudden
      infant death in Norway?

PMID- 7720753
TI  - Normal growth, despite renal failure, in a child with Sotos syndrome.

PMID- 7720754
TI  - Idiopathic pulmonary haemosiderosis.

PMID- 7720756
TI  - Mitral and aortic regurgitation in 84 patients with mucopolysaccharidoses.
AB  - In echocardiographic and necropsy studies nodular thickening of the mitral valve
      and, less frequently, of the aortic valve has been found in 60%-90% of patients
      with mucopolysaccharidoses (MPS). Little is known about the haemodynamic
      consequences of these morphological changes. In this study 84 unselected patients
      with different enzymatically proven MPS and 84 age and sex matched, healthy
      persons were studied prospectively by colour Doppler flow mapping. The patients'
      age ranged from 1 to 47 years (median 8.1 years). Mitral and aortic regurgitation
      were defined as a holosystolic or holodiastolic jet originating from the valve
      into the left atrium or the left ventricular outflow tract, respectively, with
      peak velocities exceeding 2.5 m/s. Of the 84 patients with satisfactory studies,
      mitral regurgitation was detected in 64.3% and aortic regurgitation in 40.5%,
      respectively. Regurgitation was severe in 4.8% of mitral valves and 8.3% of
      aortic valves. The frequency of aortic and/or mitral regurgitation was 75% in all
      patients, 89% in MPS I, 94% in MPS II, 66% in MPS III, 33% in MPS IV, and 100% in
      MPS VI. Combined mitral and aortic regurgitation was present in 29% of our
      patients. None of the control persons showed mitral or aortic regurgitation.
      CONCLUSION: Aortic and mitral regurgitation are more frequent in patients with
      MPS than previously thought and that therefore these patients should have regular
      colour Doppler flow mapping and antibiotic prophylaxis when required.

PMID- 7720755
TI  - Bacterial meningitis: mechanisms of disease and therapy.
AB  - Bacterial meningitis continues to be a serious infectious disease with a high
      morbidity and mortality in young children. Early recognition and initiation of
      adequate treatment are the major determinants for a good outcome. Recent advances
      in our understanding of the host inflammatory response by cytokines may result in
      the use of new therapeutic strategies. Such modulation of the inflammatory
      response may reduce the incidence of sequelae and death. The use of steroids as
      adjunctive therapy in children with bacterial meningitis probably has beneficial
      effects although the available data are still controversial. Additionally,
      studies in experimental meningitis models indicate that non-steroidal anti
      inflammatory drugs and monoclonal antibodies against bacterial products,
      cytokines and CD18 on leucocytes reduce the extent of the meningeal inflammation.
      Human studies to evaluate the efficacy of these immune modulators are expected to
      start soon. However, prevention of bacterial meningitis by conjugate vaccines
      against Streptococcus pneumoniae and Neisseria meningitidis will be the most
      promising development in the next decade.

PMID- 7720757
TI  - Drug prescription attitudes and behaviour of general practitioners. Effects of a
      problem-oriented educational programme.
AB  - A producer-independent, problem-oriented, group-education programme with 2-day
      meetings on drug treatment in primary health care (PHC) was developed and
      evaluated. Initially, it was tested on a selected group of general practitioners
      (district physicians), using a non-exposed group as control. A comprehensive
      questionnaire was used to test changes in attitudes. There was a significant
      change in attitudes concerning both general opinions on drugs and drug use, on
      information about drug treatment, and on use of drugs in selected therapeutic
      areas. Also, the district physicians became more critical towards information
      from pharmaceutical companies. Prescribing patterns tended to change in
      accordance with the attitude changes. Subsequently, the programme was offered to
      all district physicians (about 550) in the southern Swedish health care region
      for a 10-year period, with 20-25 district physicians per 2-day meeting. The
      impact of the programme on the prescribing of a selected group of drugs
      (antibiotics) was assessed by voluntary registration of prescription by the
      participants, by regional prescription analyses and by analyses of drug sales
      data. There were significant, consistent, and sustained changes in the
      prescribing of antibiotics. The study supports the view that, if drug prescribing
      in general practice is to be improved, producer-independent, problem-oriented,
      face-to-face, small-group education on drug treatment is worthwhile.

PMID- 7720758
TI  - Effect of captopril on myocardial beta-adrenoceptor density and Gi alpha-proteins
      in patients with mild to moderate heart failure due to dilated cardiomyopathy.
AB  - In end-stage heart failure due to idiopathic dilated cardiomyopathy beta 1
      adrenoceptors are downregulated and Gi alpha-proteins are upregulated. The aim of
      the present study was to investigate the influence of the angiotensin-converting
      enzyme inhibitor captopril on beta-adrenoceptor density and Gi alpha-proteins in
      sequential endomyocardial biopsies. Nineteen patients with mild to moderate
      congestive heart failure due to idiopathic dilated cardiomyopathy (NYHA Class II
      III) were studied before and after 8-11 weeks of therapy. Patients were
      randomised into a captopril and a control group; 9 patients received captopril
      12.5-50 mg per day, (divided in 2-3 doses) p.o. in addition to "conventional"
      therapy with digoxin and diuretics, and 10 controls received "conventional"
      therapy only. Echocardiography, spiroergometry, right heart catheterisation and
      endomyocardial biopsies were performed before (baseline) and after treatment.
      Compared to baseline, captopril increased total beta-adrenoceptor density by
      selectively increasing beta 1-adrenoceptors (31.6 vs 41.2 fmol.mg-1; p < 0.05)
      but had no significant effect on Gi alpha-proteins. The results indicate that
      treatment with angiotensin-converting enzyme inhibitors partly restores
      myocardial beta 1-adrenoceptor density, and this action effect may contribute to
      the clinical improvement of patients with idiopathic dilated cardiomyopathy
      treated in this way.

PMID- 7720759
TI  - Natriuretic and diuretic effects of felodipine and hydrochlorothiazide after
      single and repeated doses.
AB  - The effects of the calcium antagonist, felodipine, and hydrochlorothiazide (HCTZ)
      on natriuresis/diuresis and blood pressure were evaluated in 12 healthy subjects.
      The investigation was designed as a double-blind, three-way, randomised,
      crossover study, and all comparisons were performed against placebo. Urine
      volume, urine sodium excretion, heart rate and blood pressure were measured after
      a single dose of felodipine 10 mg, HCTZ 12.5 mg or placebo as well as during
      steady-state conditions (6 days of treatment with felodipine 10 mg b.i.d., HCTZ
      12.5 mg b.i.d. or placebo). A significant increase in natriuresis was seen in the
      first 4 h after a single dose of felodipine and HCTZ, and the effect of
      felodipine was approximately 40% that of HCTZ. When the entire 24-h period after
      a single dose was studied, there was a significant increase in natriuresis after
      HCTZ, but not after felodipine, compared with placebo. A significant increase in
      diuresis was found in the first 4 h after a single dose of HCTZ, but not after
      felodipine, compared with placebo. Under steady-state conditions, there were no
      statistically significant differences between felodipine and placebo or HCTZ and
      placebo when the 24-h period, as a whole was considered. Potassium excretion was
      not affected by any of the drugs. Felodipine caused a significant decrease in
      diastolic blood pressure in this study. This was not the case for HCTZ or
      placebo.

PMID- 7720760
TI  - Influence and interference of isosorbide dinitrate and food intake on superior
      mesenteric artery impedance in humans.
AB  - The influence of isosorbide dinitrate (ISDN) and food ingestion on superior
      mesenteric artery impedance was investigated in 24 healthy volunteers (age 40 +/-
      2.7 years). Superior mesenteric artery circulation was assessed by duplex
      ultrasound. Pulsatility index (PI) was considered as a parameter of vascular
      resistance and was calculated as the peak-to-peak amplitude of the waveform
      divided by the mean amplitude. The subjects were randomly allocated to four
      groups (ISDN, meal, ISDN + meal, meal + ISDN). PI measurements were performed in
      resting and fasting conditions and serially for 1 h after sublingual 5 mg ISDN,
      ingestion of a 300-kcal, 300-ml mixed liquid meal; sublingual 5 mg ISDN followed
      10 min later by the test meal; and ingestion of the test meal followed 5 min
      later by sublingual 5 mg ISDN. Five minutes after 5 mg sublingual ISDN, PI had
      increased from 6.8 to 12.4, while after intake of a meal PI had decreased from
      7.6 to 4.9. Separate effects of 5 mg ISDN and meal intake lasted for at least 1
      h. The reflex vasoconstrictive effect of 5 mg ISDN on the superior mesenteric
      artery circulation was counterbalanced by ingestion of a meal in healthy
      volunteers.

PMID- 7720761
TI  - Identical efficacy of terbutaline multidose dry powder inhaler prior to and after
      4 weeks of use by asthmatic patients.
AB  - We investigated whether the terbutaline multidose dry powder inhaler (Turbuhaler)
      has the same efficacy after routine daily use as it has when new. Thirty-three
      adult asthmatic patients were tested on two occasions. The bronchodilatory effect
      of inhalations of 0.5, 0.5 and 1.0 mg terbutaline at 40-min intervals from the
      same device was determined prior to and after using the device at least three
      times a day for 4 weeks. When tested for the second time, 116-186 doses had been
      inhaled. Although baseline forced expiratory volume in 1 s (FEV1) was slightly
      higher after the 4-week treatment period, the bronchodilatory effect of the
      inhaled terbutaline doses was identical. We conclude that the multidose dry
      powder inhaler is as effective in delivering terbutaline after a period of
      routine daily use as it is when new.

PMID- 7720762
TI  - Acute effects of low dose nicotine gum on platelet function in non-smoking
      hypertensive and normotensive men.
AB  - Twenty non-smoking middle-aged men with mild untreated essential hypertension
      were compared to age-matched controls (n = 22) in a double-blind placebo
      controlled study. Plasma and urinary concentrations of the platelet-specific
      protein beta-thromboglobulin (beta-TG), platelet count and mean platelet volume
      were measured before and after chewing 2 mg nicotine gum. The mean plasma
      nicotine concentration increased to 4.3 ng/ml in the hypertensive group and to
      3.9 ng/ml in the normotensive group after 30 minutes of chewing the nicotine gum.
      Blood pressure and heart rate increased significantly, but there was no
      difference between the groups. Venous plasma catecholamine concentrations were
      unchanged. beta-TG concentrations in plasma and urine were similar in the two
      groups, and plasma beta-TG levels did not change after nicotine gum in either
      group. Urinary high molecular weight beta-TG decreased after nicotine compared to
      placebo. Platelet count and volume increased significantly in the hypertensive
      group, but not in the normotensive group. The response in platelet count was
      significantly higher in the hypertensive group. Thus, small amounts of nicotine
      increase platelet counts more in hypertensive than in normotensive non-smoking
      men, without inducing the platelet release reaction.

PMID- 7720763
TI  - Upper limit of plasma alanine amino transferase during phase I studies.
AB  - In Phase I clinical studies, the maximum tolerated dose has to be determined by a
      case by case analysis sometimes using a laboratory adverse effect, e.g. an
      increase in alanine amino transferase (ALT). For this reason a threshold to
      discriminate between significant or non significant adverse changes in ALT is
      required particularly in Phase I studies, in order to deal with the very common
      "close to the limit values". Previous methods (limit of normal range or normal
      range plus an arbitrary margin) do not solve this problem. The authors propose a
      new method taking into account the threshold used as inclusion criteria for ALT
      (R) and the range of spontaneous variations measured under identical Phase I
      study conditions (V). The (R) and (V) thresholds, respectively, are defined as 50
      IU.l-1 and a 50% increase, from baseline. Thus an ALT value is recognized as a
      "significant adverse experience" if it exceeds 50 IU.l-1 above an increase from
      baseline exceeding 50% of the baseline value. To highlight the value of the
      method, it was implemented in a one year period including 8 studies and 134
      subjects. The sensitivity, specificity and positive predictive value of various
      methods were compared. The results showed the following: Six out of 134 subjects
      had significant adverse changes in ALT (4%); and all these 6 subjects were
      detected by the proposed new method without error. Eight subjects including two
      false positives, were detected by an use of the normal range limit, and only 4
      were detected using, the 10% margin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720764
TI  - A population and family study of CYP1A2 using caffeine urinary metabolites.
AB  - CYP1A2 is a cytochrome P450 which is inducible by polycyclic aromatic
      hydrocarbons. This induction could be mediated via the Ah locus, which encodes a
      cytosolic receptor responsible for the regulation of the CYP1A1 gene. Enzyme
      activity in vivo can be measured by the urinary caffeine metabolite ratio (AFMU +
      1X + 1U)/17U. Our goal was to determine, using this ratio, the possible existence
      of a genetic polymorphism in CYP1A2 induction. For this purpose, a population and
      family study, including smokers, were undertaken. In a first step, we
      investigated factors influencing enzyme activity in a population of 245 unrelated
      individuals. The induction effect of smoking and inhibiting effect of oral
      contraceptive use were confirmed. None of the other factors examined (age, sex,
      level of cigarette consumption, nicotine or tar amounts, filter, inhalation)
      accounted for the interindividual variability in the metabolic ratio. Using the
      statistical SKUMIX method, a unimodal (one peak) distribution of the ratio was
      concluded in 164 unrelated smokers, since a second distribution did not
      significantly improve the fit to the data (chi 2(1) = 1.39, P > 0.2). Segregation
      analysis was performed on 68 nuclear families and no major gene effect could be
      shown. Furthermore, the polygenic model did not provide a higher likelihood than
      the sporadic one, which argues against the existence of any familial resemblance.
      Although we cannot rule out the possibility that some environmental factors could
      obscure the phenotypes and occult a genetic determinism, we conclude that genetic
      factors are probably negligible in the determination of CYP1A2 activity measured
      by this method.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720765
TI  - Induction of cytochrome P4501A by smoking or omeprazole in comparison with UDP
      glucuronosyltransferase in biopsies of human duodenal mucosa.
AB  - Drug-metabolizing enzymes were investigated in duodenal biopsy specimens.
      Cytochrome P4501A (CYP1A) activity was determined by measuring 7-ethoxyresorufin
      O-deethylase (EROD) activity in biopsies from 20 smokers (3-30 cigarettes per
      day), 21 nonsmokers, and 10 nonsmokers receiving omeprazole treatment (20-60
      mg/day for at least 1 week). Omeprazole is known to act as a polycyclic aromatic
      hydrocarbon (PAH)-type inducer in humans. EROD activity was found to be
      significantly induced in smokers and omeprazole-treated patients, with medians of
      2.1 and 1.1 pmol.min-1.mg protein-1, respectively, compared with 0.5 pmol.min
      1.mg protein-1 in nonsmokers. Immunoblot analysis substantiated that EROD
      activity was correlated with CYP1A protein. In contrast, UDP
      glucuronosyltransferase (UGT) activity towards 4-methylumbelliferone (an
      overlapping substrate of several constitutive and inducible UGTs) was not
      significantly affected. The results demonstrate CYP1A induction by omeprazole and
      by constituents of cigarette smoke in the human duodenum and support the utility
      of duodenal biopsies to monitor CYP1A induction by PAH-type inducers.

PMID- 7720766
TI  - Clinical pharmacological equivalence of a novel FCH-free GTN spray with low
      ethanol content vs a FCH-containing GTN spray.
AB  - The overall therapeutic equivalence of a fluorochlorohydrocarbon (FCH)-free
      glyceryl trinitrate (GTN) pump spray with a low ethanol content (TL) was
      investigated relative to an FCH-containing GTN spray (Nitrolingual; R), in terms
      of: (1) pharmacokinetic bioavailability, (2) pharmacodynamic responses as
      assessed by digital plethysmography (DPG), and (3) clinical perception upon
      application. Pharmacokinetically, the time courses of the plasma concentrations
      of GTN and its dinitrate metabolites, 1,2- and 1,3-GDN, subsequent to the
      sublingual administration of 0.8 mg GTN showed somewhat lower bioavailability of
      GTN and its metabolites than to the reference. Pharmacodynamically, the changes
      in the DPG signals after the application of 0.8 mg GTN with TL were
      biostatistically equivalent with R (estimated ratio TL/R for the maximum decrease
      of the ratio between the systolic a wave and c incisure: 0.98; 90% CI: 0.84-1.14;
      and for the average decrease of the c: a ratio: 0.97; 90% CI: 0.80-1.16). The
      time of occurrence of the maximum effect of TL was not significantly different
      from that of R (estimated difference TL-R: -2.25 min; 95% CI:-9.5 min to 2 min).
      In contrast, after the administration of an FCH-free GTN spray with a higher
      ethanol content (TH, active control), the effect had a slightly earlier onset (TH
      R: -6 min, 95% CI:-9.5 to -2 min) and there was a higher average response (TH/R:
      1.12: 90% CI: 0.95 to 1.34). However, TH was consistently judged to cause an
      extremely unpleasant burning sensation in the mouth and thus was perceived as
      distinctly different from R. In contrast, TL was well tolerated and could not be
      distinguished from R.

PMID- 7720767
TI  - CSF concentrations and clinical effects following intravenous dixyrazine
      premedication.
AB  - Single concurrent plasma and lumbar spinal fluid samples were collected from
      twenty-two patients given IV dixyrazine 0.15 mg/kg, 10-106 min earlier in an open
      study. Dixyrazine penetrated rapidly into the spinal fluid; the CSF/P ratio was
      0.3 by 10 min after drug administration and persisted at that level during the
      study period. The uncontrolled sedative and anxiolytic effects assessed by the
      patients were slight, and were correlated with the CSF drug concentrations only
      during the first 30 min after medication.

PMID- 7720768
TI  - Variable activation of lovastatin by hydrolytic enzymes in human plasma and
      liver. 4.
AB  - Lovastatin, widely used to lower cholesterol, is a pro-drug that requires
      metabolic activation through hydrolysis by carboxyesterases. There appear to be
      at least three distinct esterases in humans capable of catalysing this reaction,
      one in plasma and two in the liver. The rate of lovastatin hydroxy acid formation
      was measured as 15.8 pmol.ml-1.min-1 in plasma, 2.13 pmol.mg-1 protein.min-1 in
      hepatic microsomes and 0.92 pmol.mg-1 protein.min-1 in cytosol. The data suggest
      that on average the three esterases together are capable of activating about 220
      nmol (90 micrograms) lovastatin per minute per person, to which the esterases of
      plasma, liver microsomes and liver cytosol contribute approximately 18, 15 and
      67%, respectively. All three esterases showed evidence of inter-individual
      variability. In one of 17 livers, both cytosolic and microsomal esterase activity
      was completely missing, while two other liver specimens lacked one esterase. Such
      variability must be expected to influence the therapeutic efficacy of the drug,
      and they might be related to its occasional toxicity.

PMID- 7720769
TI  - Whole-blood pharmacokinetics and metabolic effects of the topical carbonic
      anhydrase inhibitor dorzolamide.
AB  - Following a single-dose, open-label, pilot pharmacokinetic study in six subjects,
      the systemic pharmacokinetics and metabolic effects of dorzolamide after topical
      ocular administration were investigated in a double-blind, randomised, placebo
      controlled study in 12 healthy volunteers. The subjects received a controlled
      diet on the 5 days before treatment initiation and throughout the study. For 14
      days, a bilateral q.i.d. regimen of 3% dorzolamide, consisting of approximately
      7.7 micrograms per day (21.3 mumol) dorzolamide hydrochloride, or placebo was
      given. Blood and urine electrolytes and acid-base profiles were measured 1 day
      prior to treatment and on days 1, 7 and 14 of treatment, and 24-h urine samples
      were collected daily. Topically applied dorzolamide was slowly taken up in
      erythrocytes and eliminated with a half life of approximately 120 days. Compared
      to the pre-study values, no significant treatment effect was observed in either
      the daily profiles or the 14-day cumulative sodium, potassium and citrate
      excretions. Two other volunteers given acetazolamide (125 mg q.i.d.) and assessed
      with the identical set of observations demonstrated marked metabolic changes. In
      spite of the prolonged and marked inhibition of carbonic anhydrase in red blood
      cells by dorzolamide, clinically significant metabolic and renal effects were not
      observed. The ocular tolerability profile was acceptable to all subjects.

PMID- 7720770
TI  - Serum sex hormone levels after replacing carbamazepine with oxcarbazepine.
AB  - The function of the hepatic P450 enzyme system was evaluated by measuring the
      kinetics of antipyrine and serum sex hormone levels were determined in 12 male
      patients with epilepsy during carbamazepine medication, and two and six months
      after changing their medication to oxcarbazepine. Antipyrine t1/2 increased and
      antipyrine CL decreased after the change reflecting normalisation of the liver
      P450 enzyme system function. Serum sex hormone binding globulin levels decreased,
      and serum dehydroepiandrosterone sulphate increased after the change. The results
      show that the carbamazepine-associated induction of the liver P450 enzyme system
      and changes in serum sex hormone balance can be avoided by replacing
      carbamazepine with oxcarbazepine.

PMID- 7720771
TI  - The protective effect of transdermal broxaterol on exercise-induced
      bronchoconstriction.

PMID- 7720772
TI  - CNS research in the pharmaceutical industry. A personal view of how innovation
      could be promoted by clinical pharmacology.

PMID- 7720773
TI  - Differential regulation by beta-amyloid peptides of intracellular free Ca2+
      concentration in cultured rat microglia.
AB  - We have previously shown that exposure to beta-amyloid peptides alters microglial
      activity and viability. It is thought that beta-amyloid peptides induce toxicity
      in neuronal cultures by destabilizing Ca2+ homeostasis. To investigate the
      effects of beta-amyloid peptides on intracellular free Ca2+ concentration
      ([Ca2+]i) in cultured microglia, we used Fura-2 imaging. Exposure to 25 microM
      beta-amyloid-(25-35) induced increases in 2+]i within 1 h. In contrast, exposure
      to 25 microM beta-amyloid-(1-42), the full-length homolog to the beta-amyloid
      protein deposited in plaques, does not, over the same time period. However, the
      average [Ca2+]i of microglia is increased by a 6 h exposure to beta-amyloid-(1
      42). Thus, beta-amyloid-(25-35) can alter [Ca2+]i in microglia on a different
      time scale than beta-amyloid-(1-42), indicating a specificity in the response of
      these cells as compared to neurons.

PMID- 7720774
TI  - Modulation of cytosolic Ca2+ concentration by thapsigargin and cyclopiazonic acid
      in human aortic endothelial cells.
AB  - To clarify the agonist-induced Ca2+ entry mechanism, effects of thapsigargin and
      cyclopiazonic acid, selective inhibitors of endoplasmic reticulum Ca(2+)-ATPase,
      on intracellular free Ca2+ concentration ([Ca2+]i) were studied in cultured human
      aortic endothelial cells loaded with the fluorescent Ca2+ indicator fura-2.
      Thapsigargin (1-1000 nM) and cyclopiazonic acid (0.1-100 microM) produced a
      biphasic change in [Ca2+]i, which consisted of a transient peak elevation
      followed by a long-lasting decline of [Ca2+]i in a concentration-dependent
      manner. In the presence of thapsigargin or cyclopiazonic acid, the rapid
      transient elevation of [Ca2+]i elicited by histamine was attenuated in a time
      dependent manner. The slow declining phase of the response to thapsigargin and
      cyclopiazonic acid was completely eliminated by removal of extracellular Ca2+,
      and it was also prevented by reduction of the extracellular Cl- concentration to
      40 mM or by the Cl- channel blocker N-phenylanthranilic acid. These findings
      suggest that the initial transient rising phase and the slow declining phase of
      [Ca2+]i in response to thapsigargin and cyclopiazonic acid reflect a blockade of
      Ca2+ uptake into the endoplasmic reticulum and the Cl(-)-sensitive Ca2+ entry
      activated by the depletion of agonist-sensitive intracellular Ca2+ stores,
      respectively, in human aortic endothelial cells.

PMID- 7720775
TI  - Alpha 1-adrenoceptor subtypes mediating stimulation of Na+,K(+)-ATPase activity
      in rat renal proximal tubules.
AB  - Although both alpha 1A- and alpha 1B-adrenoceptors are present in renal proximal
      tubules, the involvement of these receptor subtypes in the stimulation of
      Na+,K(+)-ATPase activity is not known. This study was undertaken to delineate the
      receptor subtype(s) involved in alpha 1-adrenoceptor-mediated increase in
      Na+,K(+)-ATPase activity and to identify the cellular signaling mechanisms such
      as stimulation of inositol triphosphate formation (IP3) and protein kinase C
      activation in this phenomenon. It was found that norepinephrine-induced increase
      in Na+,K(+)-ATPase activity was attenuated by prazosin, but not by rauwolscine,
      indicating the involvement of alpha 1-adrenoceptors. Furthermore, this response
      was selectively inhibited by the alpha 1B-adrenoceptor inactivator,
      chloroethylclonidine (100 microM), but not by the alpha 1A-adrenoceptor
      antagonist, WB4101 (0.01 microM). We examined whether these effects on Na+,K(+)
      ATPase activity are mediated via the activation of IP3 and protein kinase C.
      Phenylephrine-induced increase in IP3 levels was abolished by prazosin, and
      significantly inhibited by WB4101, but not by chloroethylclonidine. Similarly,
      phenylephrine-induced activation of protein kinase C was sensitive to blockade by
      WB4101, but not by chloroethylclonidine. These results suggest that whereas both
      alpha 1A- and alpha 1B-adrenoceptors are present in proximal tubules, alpha 1B
      adrenoceptors are involved in stimulating Na+,K(+)-ATPase activity and alpha 1A
      adrenoceptors are predominantly linked to renal tubular IP3 production and
      protein kinase C activation. Therefore, it appears that norepinephrine-induced
      stimulation of Na+,K(+)-ATPase activity does not involve phospholipase-C-coupled
      protein kinase C pathway.

PMID- 7720776
TI  - Role of calcium ion in platelet serotonin uptake regulation.
AB  - It is generally accepted that intracellular Ca2+ is a key substance in the
      intracellular signal transducing mechanism of platelets. We investigated the
      possibility that extracellular and/or intracellular Ca2+ might regulate the
      transport activity of serotonin (5-HT) into platelets. We found that
      extracellular Ca2+ chelation with EGTA caused inhibition of 5HT uptake activity,
      which was recovered by extracellulary applied excess Ca2+. Intracellular Ca2+
      chelation with acetoxymethyl bis(O-aminophenoxy)ethane-N,N,N'-tetraacetate (BAPTA
      AM) did not, however, have any inhibitory effect on 5HT uptake activity in the
      presence of extracellular Ca2+. In the absence of extracellular Ca2+, BAPTA-AM
      significantly inhibited 5-HT uptake. The restorative effect of Ca2+ on 5-HT
      transport into EGTA-treated platelets was mimicked by Ba2+, but not by Sr2+. It
      was antagonised by inorganic Ca2+ channel antagonist including Ni2+, La3+ and
      Gd3+, but not by organic Ca2+ channel blockers including verapamil, nifedipine,
      diltiazem, omega-conotoxin GVIA and omega-agatoxin IVA. Furthermore, 3,4,5
      trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8), an
      intracellular Ca2+ antagonist, was found to inhibit the restorative effect of
      Ca2+. These results have led to the suggestion that depletion of intracellular
      Ca2+ pool(s) by EGTA might result in a reduction of 5-HT uptake activity. Thus,
      the intracellular Ca2+ pool(s) susceptible to EGTA might have a regulatory role
      in maintaining 5-HT transport into blood platelets.

PMID- 7720777
TI  - Neuroactive steroid modulation of [3H]muscimol binding to the GABAA receptor
      complex in rat cortex.
AB  - Epalons are a subclass of neuroactive steroids which are positive allosteric
      modulators of the GABAA receptor acting via a unique site on the receptor
      complex. Enhancement of [3H]muscimol binding to the GABA recognition site was
      observed to be either full (> 150%) or limited (110-135%) and specific for
      epalons. Both one and two component modulation was observed. Saturation studies
      performed in the presence of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5
      alpha-P) showed that 3 alpha, 5 alpha-P increased the density of high affinity
      [3H]muscimol sites and doubled the affinity of low affinity sites. 3 alpha,5
      alpha-P had no effect on the affinity of the high affinity site or the density of
      the low affinity site. These data indicate that: (1) epalons are potent,
      stereoselective enhancers of [3H]muscimol binding; (2) epalons display varying
      levels of efficacy and some exhibit two-component enhancement; and (3) 3 alpha,5
      alpha-P enhancement of [3H]muscimol binding results from both an increased
      density of high affinity sites and an increased affinity for low affinity sites.

PMID- 7720778
TI  - Staurosporine affects calcium homeostasis in cultured bovine adrenal chromaffin
      cells.
AB  - These studies show that the potent, non-specific, protein kinase inhibitor,
      staurosporine, disrupts Ca2+ homeostasis in cultured bovine adrenal chromaffin
      cells. Staurosporine treatment reduces basal and A23187-stimulated catecholamine
      release from chromaffin cells, but does not inhibit activated Ca2+ influx.
      Furthermore, pretreatment with staurosporine also reduces Ca(2+)-stimulated
      catecholamine release from digitonin-permeabilized cells (t1/2, 40.6 min; IC50,
      66.0 nm). However, staurosporine does not inhibit the rise in intracellular Ca2+
      ([Ca2+]i) in response to nicotine stimulation as measured by fura-2 photometry.
      These studies demonstrate that staurosporine interferes with the secretory
      process at some step at or after the rise in [Ca2+]i in adrenal chromaffin cells.
      Examination of the effects of staurosporine on 45Ca2+ movement shows that
      staurosporine produces a slowly developing basal 45Ca2+ accumulation; after 30
      min no significant change is observed, but by 120 min, 45Ca2+ accumulation is
      increased by 29.5%. Thapsigargin and 2,5-di-(tert-butyl)-1,4-benzohydroquinone
      (tBHQ), inhibitors of Ca(2+) ATPases, were used to determine whether
      staurosporine induced 45Ca2+ accumulation results from sequestration of 45Ca2+
      within intracellular stores. While thapsigargin has no significant effect,
      concomitant treatment with tBHQ prevents the increase in 45Ca2+ uptake associated
      with staurosporine treatment. Therefore, the tBHQ-sensitive Ca2+ store, but not
      the thapsigargin/inositol 1,4,5-triphosphate-sensitive Ca2+ store, appears to be
      staurosporine-sensitive. Overall, these studies indicate that staurosporine
      reduces catecholamine release by interfering with Ca2+ homeostasis. Furthermore,
      this work suggests that a staurosporine-sensitive phosphoprotein(s) is involved
      with the regulation of Ca2+ homeostasis in bovine adrenal chromaffin cells.

PMID- 7720779
TI  - The selective 5-HT1A antagonist radioligand [3H]WAY 100635 labels both G-protein
      coupled and free 5-HT1A receptors in rat brain membranes.
AB  - The tritiated derivative of the novel silent 5-HT1A receptor antagonist WAY
      100635 [N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)
      cyclohexane carboxamide] was tested as a potential radioligand of 5-HT1A
      receptors in the rat brain. Binding assays with membranes from various brain
      regions showed that [3H]WAY 100635 specifically bound to a homogeneous population
      of sites, with a Kd of 0.10 nM. The regional distribution of [3H]WAY 100635
      specific binding sites, as assessed in membrane binding assays and by
      autoradiography of labelled brain sections, superimposed exactly over that of 5
      HT1A receptors specifically labelled by [3H]8-hydroxy-2-(di-n-propylamino)
      tetralin ([3H]8-OH-DPAT). Furthermore, the positive correlation (r = 0.96)
      between the respective pKi values of a large series of ligands as inhibitors of
      the specific binding of [3H]WAY 100635 and [3H]8-OH-DPAT in hippocampal membranes
      indicated that their pharmacological properties were similar. Nevertheless,
      marked differences also existed between [3H]8-OH-DPAT and [3H]WAY 100635 specific
      binding, as the former was inhibited by 1-100 microM GTP and GppNHp, whereas the
      latter was enhanced by these guanine nucleotides. In contrast, Mn2+ (1-10 mM)
      increased the specific binding of [3H]8-OH-DPAT, but inhibited that of [3H]WAY
      100635. Treatment of membranes with N-ethylmaleimide (1-5 mM) markedly reduced
      their capacity to specifically bind [3H]8-OH-DPAT, but slightly increased (at 1
      mM) or did not affect (at 5 mM) their [3H]WAY 100635 specific binding capacity.
      Finally, the Bmax of [3H]WAY 100635 specific binding sites was regularly 50-60%
      higher than that of [3H]8-OH-DPAT in the same membrane preparations from various
      brain regions (hippocampus, septum, cerebral cortex). These data are compatible
      with the idea that whereas [3H]8-OH-DPAT only binds to G-protein-coupled 5-HT1A
      receptors, [3H]WAY 100635 is a high affinity ligand of both G-protein-coupled and
      free 5-HT1A receptor binding subunits in brain membranes.

PMID- 7720780
TI  - Interaction of pristinamycin IA with P-glycoprotein in human intestinal
      epithelial cells.
AB  - Pristinamycin IA is a cyclo-peptidic macrolactone antibiotic belonging to the
      streptogramin family. In the present work, the interaction of pristinamycin IA
      with the multidrug transporter P-glycoprotein was investigated in the
      differentiated human intestinal epithelial cell line Caco-2. Pristinamycin IA
      specifically inhibited the efflux of the P-glycoprotein substrate
      [3H]vinblastine, thus increasing the cellular accumulation of the drug.
      Pristinamycin IA also reduced by 70% the basolateral to apical secretion of
      [3H]vinblastine across Caco-2 cell monolayers. The cellular accumulation of
      [14C]pristinamycin IA was very low and was increased by P-glycoprotein inhibitors
      (verapamil, chlorpromazine and reserpine). The basolateral to apical transport of
      [14C]pristinamycin IA was 100-fold higher than apical to basolateral passage.
      This polarized transport was inhibited by verapamil and by ATP depletion. The
      results suggest that pristinamycin IA is a substrate for the P-glycoprotein, a
      finding which may have important consequences for the pharmacokinetics of this
      drug.

PMID- 7720781
TI  - Contrasting effects of calyculin A and okadaic acid on the respiratory burst of
      human neutrophils.
AB  - The involvement of serine/threonine protein-phosphatases in the production of
      superoxide (respiratory burst) by human neutrophils was investigated using
      calyculin A, a potent inhibitor of both protein phosphatases type 1 and 2A, and
      okadaic acid, which preferentially inhibits protein phosphatase type 2A.
      Treatment of neutrophils with calyculin A (25-75 nM) or okadaic acid (1-4 microM)
      had no stimulatory effect but potently enhanced total superoxide production
      induced by an optimal fMLP (N-formyl-methionyl-leucyl-phenylalanine)
      concentration (0.1 microM). The maximum increase plateaued with 50-75 nM
      calyculin A and 2-4 microM okadaic acid, reaching approximately 120 and 200% of
      control values, respectively. Unlike calyculin A, okadaic acid also primed the
      initial rate of superoxide production, suggesting that protein phosphatases may
      down-regulate both initiation and termination of respiratory burst. Optimal
      stimulation of the respiratory burst by PMA (160 nM) was inhibited by calyculin A
      and okadaic acid, with an IC50 of 60 nM and 2 microM, respectively, although both
      drugs caused protein hyperphosphorylation. The inhibition was partially prevented
      by a nonstimulatory concentration of A23187, indicating a role of calcium in the
      inhibitory effects of the drugs. Unlike the optimal respiratory burst, suboptimal
      respiratory burst induced by PMA (1-7 nM) was enhanced by calyculin A and okadaic
      acid. Unprimed and primed respiratory bursts were depressed by a selective
      antagonist of protein kinase C (GF 109203X), indicating positive regulation of
      these responses by protein kinase C. Thus, the use of calyculin A and okadaic
      acid distinguishes two regulatory processes of superoxide production.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7720782
TI  - Fe(2+)-mediated binding of serotonin and dopamine to skeletal muscle actin:
      resemblance to serotonin binding proteins.
AB  - Fe2+ stimulates the binding of [3H]serotonin and [3H]dopamine to rabbit skeletal
      muscle actin. This binding is inhibited by reducing agents (sodium ascorbate,
      vitamin E), by superoxide dismutase and by sulfhydryl group-modifying reagents (N
      ethyl-maleimide, 2,2'-dinitro-5,5'-dithiobenzoic acid). The effect of Fe2+ is
      mimicked by oxidants (sodium periodate, potassium nitroso-disulfonate) and by
      superoxide radicals. Once formed, the binding cannot be decreased by a large
      excess of monoamine. It is proposed that Fe2+ catalyses the autoxidation of the
      monoamines by generating oxygen free radicals, and the oxidation products are
      likely to bind covalently to exposed cysteine residues of actin. Digestion of
      [3H]dopamine-labelled actin by cyanogen bromide and then by V8 protease
      (EC3.4.21.19) yields two labelled peptides whose apparent molecular weights (4.1
      and 1.2 kDa) are compatible with the labelling of cysteine-10 and -374. Fe2+ also
      inactivates some of the binding sites on actin. This inactivation, and the
      covalent nature of the binding precludes the interpretation of monoamine
      saturation and competition binding data in terms of reversible bimolecular
      interactions.

PMID- 7720783
TI  - Potentiation of growth inhibition due to vincristine by ascorbic acid in a
      resistant human non-small cell lung cancer cell line.
AB  - A human cell subline (PC-9/VCR) resistant to vincristine was established from non
      small cell lung cancer PC-9 cells by incremental exposure of the cells to
      vincristine. The resistant cells showed phenotypic resistance to vincristine (10
      fold), colchicine (6.9-fold) and cisplatin (1.4-fold) but they showed sensitivity
      to other chemotherapeutic agents including melphalan and etoposide VP-16. The
      characteristics of the vincristine resistance was partially inhibited (5-7-fold)
      by co-treatment of PC-9/VCR cells with a nontoxic concentration of L-ascorbic
      acid (25 micrograms/ml). Co-treatment or 96 h pre-treatment with ascorbic acid
      resulted in potentiation of the vincristine effect on the resistant, but not on
      the sensitive, cell line. The growth inhibition due to vincristine treatment
      after 24 or 96 h growth in ascorbic acid-free medium was decreased in the
      resistant as well as in the sensitive cell line. In both cell lines, enhanced
      growth rate has been shown after ascorbic acid treatment. Similarly, cross
      resistance of PC-9/VCR cells to colchicine could also be blocked by ascorbic
      acid. In addition, a nontoxic concentration of verapamil, a known multidrug
      resistance inhibitor, did not affect the resistant phenotype of PC-9/VCR cells.
      These findings suggest that an ascorbic acid-sensitive mechanism may be involved
      in drug resistance per se in the human lung cancer cells, which differs from the
      classical phosphoglycoprotein-mediated or previously reported non
      phosphoglycoprotein-mediated multidrug resistance.

PMID- 7720784
TI  - Neurogenic goblet cell secretion and bronchoconstriction in guinea pigs
      sensitised to trimellitic anhydride.
AB  - Trimellitic anhydride is a cause of occupational asthma in humans. We have
      previously found that tracheal instillation of trimellitic anhydride conjugated
      to guinea pig serum albumin induces acute bronchoconstriction and airway plasma
      exudation in sensitised animals, responses mediated primarily via histamine
      release. In the present study, neural mechanisms mediating bronchoconstriction
      and goblet cell secretion were determined in trimellitic anhydride-sensitised
      guinea pigs using the ganglionic blocker hexamethonium to eliminate efferent
      reflex mechanisms, pretreatment with capsaicin to eliminate afferent mechanisms,
      or cimetidine and mepyramine to eliminate histamine-mediated mechanisms. The
      magnitude of secretion of intracellular mucus from tracheal goblet cells was
      quantified morphometrically as a mucus score which is inversely related to the
      degree of discharge. Guinea pigs were injected intradermally either with 0.1 ml
      0.3% trimellitic anhydride in corn oil or with corn oil alone as control.
      Fourteen to eighteen days later all sensitised animals had developed specific
      immunoglobulin (Ig) G1 antibodies whereas the controls had not. Tracheal
      instillation of conjugated trimellitic anhydride in anaesthetised animals
      significantly increased airway lung resistance (RL) 24-fold in sensitised guinea
      pigs (34.3 +/- 7.9 cm H2O.ml-1.s) compared with controls (1.4 +/- 0.1 cm H2O.ml
      1.s). Mucus score was significantly reduced by 51% (indicating goblet cell
      secretion) in sensitised guinea pigs (183 +/- 22 mucus score units) compared with
      controls (372 +/- 41 mucus score units). The antihistamines significantly
      inhibited conjugated trimellitic anhydride-induced bronchoconstriction by 89%,
      but did not significantly affect goblet cell discharge. Hexamethonium alone did
      not significantly affect conjugated trimellitic anhydride-induced
      bronchoconstriction or goblet cell secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720785
TI  - Role of Kupffer cells in rat liver injury induced by diethyldithiocarbamate.
AB  - The hepatotoxicity of diethyldithiocarbamate was examined using an in vitro rat
      liver slice system. Concentration- and time-dependent losses of intracellular K+
      and adenosine triphosphate (ATP) levels were observed in rat liver slices
      incubated with diethyldithiocarbamate at concentrations between 1 and 10 mM over
      a 4-h period. Histological study revealed perivenous hepatocyte damage. To
      examine the involvement of Kupffer cells in diethyldithiocarbamate-induced
      cytotoxicity, rats were injected intravenously with 10 mg/kg of gadolinium
      chloride (GdCl3) which diminishes Kupffer cell function. Incubation of liver
      slice preparations from the GdCl3-treated rats with diethyldithiocarbamate showed
      marked inhibition of the cytotoxicity induced by diethyldithiocarbamate.
      Moreover, in vitro addition of manganese-superoxide dismutase, a superoxide anion
      scavenger, or dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, also
      showed potent inhibition. However, dexamethasone, an inhibitor of tumor necrosis
      factor, and N,N'-diphenyl-p-phenylenediamine (DPPD), an antioxidant, showed
      partial prevention of cytotoxicity. Formazan deposits formed as a result of nitro
      blue tetrazolium reduction were found in Kupffer cells at an early stage after
      diethyldithiocarbamate treatment, while lipid peroxidation occurred after 3 h.
      Both pretreatment with GdCl3 in vivo and addition of DMSO in vitro prevented the
      increase in lipid peroxidation within the liver slice preparations induced by
      diethyldithiocarbamate. These findings suggest that Kupffer cell function may be
      involved in the pathogenesis of diethyldithiocarbamate hepatotoxicity.

PMID- 7720786
TI  - Ethanol inhibition of Ca2+ and Na+ currents in the guinea-pig heart.
AB  - The effects of ethanol on L-type Ca2+ and fast Na+ currents (ICa and INa,
      respectively) were examined using the whole-cell patch-clamp experiments on
      guinea-pig ventricular cells. At a clinically relevant concentration of 24 mM,
      ethanol slightly but significantly shortened the action potential duration, and
      reduced the ICa by 7 +/- 4% (mean +/- S.D.). This concentration of ethanol did
      not affect INa, but a lethal concentration of ethanol (80 mM) significantly
      inhibited INa by 13 +/- 5%. The voltage dependence of INa activation was not
      affected by ethanol, whereas the inhibitions of ICa by 80 mM ethanol and INa by
      240 mM were both accompanied by a several mV shift in the channel availability
      curve toward more negative potentials, suggesting that the channels in the
      inactivated state are more susceptible to ethanol. The ICa inhibition by ethanol
      at clinically relevant concentrations could contribute to a negative inotropic
      effect, action potential shortening and development of arrhythmias, while the
      pathophysiological significance of ethanol inhibition of INa seems less
      important.

PMID- 7720787
TI  - beta-Eudesmol as an antidote for intoxication from organophosphorus
      anticholinesterase agents.
AB  - beta-Eudesmol, a sesquiterpenol present in Chinese herbs, improved the tetanic
      contraction impaired by diisopropylfluorophosphate in isolated mouse diaphragm
      preparations by an inhibition of the regenerative acetylcholine release. The
      antagonism was enhanced when a small concentration of obidoxime was present.
      Neither enzyme reactivation nor curare-like action was evident. beta-Eudesmol
      (300 mg/kg, i.p.) elevated the LD50 of diisopropylfluorophosphate (s.c.) in
      control mice from 4.2 to 6.4 mg/kg and in mice pretreated with atropine from 7.8
      to 10.6 mg/kg. In mice pretreated with atropine and obidoxime, beta-eudesmol
      showed a greater synergistic effect, increasing the LD50 from 281 to more than
      800 mg/kg. beta-Eudesmol also markedly alleviated diisopropylfluorophosphate
      induced muscle fasciculation, tremor and convulsion and prolonged the time to
      death. It is proposed that beta-eudesmol may be added to the standard antidotal
      regimen (atropine plus obidoxime) for treating organophosphate intoxication.

PMID- 7720788
TI  - Chronic parenterally administered nicotine and stress- or ethanol-induced gastric
      mucosal damage in rats.
AB  - Mini-osmotic pumps containing solutions of either 0.9% NaCl (infused at the rate
      of 0.5 microliter/h) or nicotine (infused in doses of 0.224, 1.03 or 1.88 mg/kg
      per day) were implanted s.c. into rats 12 days before experimentation. The
      alkaloid increased solid food consumption, but fluid intake and average weight
      gain were similar among the animals given saline or nicotine. Chronic nicotine
      treatment dose dependently intensified cold (4 degrees C)-restraint stress
      induced ulceration and increased mast cell degranulation. Oral administration of
      40% ethanol to nicotine-treated animals also produced greater mucosal damage;
      mast cell degranulation by ethanol was significantly worsened after alkaloid
      treatment. These findings show that the stress ulcer-intensifying action of the
      alkaloid is mainly through a systemic mechanism. In the case of ethanol-evoked
      mucosal damage, in addition to a topical effect, stimulation of the stomach wall
      ganglia is likely to participate in the exaggerated post-vagal ulcerogenic
      responses as seen in stress.

PMID- 7720789
TI  - Regulation of Na+,K(+)-ATPase alpha-subunit isoforms in rat tissues during
      hypertension.
AB  - We investigated the regulation of the protein expression of the alpha isozymes of
      Na+,K(+)-ATPase in reference to the enzyme activity in the heart, brain and
      skeletal muscle of rats during deoxycorticosterone acetate (DOCA)-salt
      hypertension. Treatment of rats with DOCA and salt for 28 days produced a
      significant increase in systolic blood pressure compared to the control groups
      which remained normotensive. Rats treated with DOCA expressed greater amounts of
      the immunoreactive alpha-1 isoform than untreated controls in whole heart
      membranes. However, the DOCA-induced increase in the alpha-1 isoform did not
      occur during DOCA-salt hypertension. There was a parallel change in the enzyme
      activity of the Na+,K(+)-ATPase and the protein expression of the alpha-1 isoform
      as a result of these treatments. We have also demonstrated that the hearts of
      DOCA-salt hypertensive rats expressed less of the alpha-2 isoform compared to the
      controls. We could not detect any alteration in the alpha-1 and alpha-2 isoforms
      of the skeletal muscle and alpha-1, alpha-2 and alpha-3 isoforms of the whole
      brain Na+,K(+)-ATPase during salt or DOCA treatments alone or DOCA-salt
      hypertension. Furthermore, the Na+,K(+)-ATPase activity was unaltered in these
      tissues during these treatments. In conclusion, cardiac Na+,K(+)-ATPase alpha
      subunit protein expression appears to be regulated during DOCA-salt hypertension.
      In the skeletal muscle and brain, tissues not subjected directly to increased
      pressure, this regulation of the Na+,K(+)-ATPase was not apparent.

PMID- 7720790
TI  - 5-Hydroxytryptamine release from platelets by different red wines: implications
      for migraine.
AB  - We have confirmed our earlier finding that most red wines are able to bring about
      5-hydroxytryptamine (5-HT, serotonin) release from platelets in vitro. Platelets
      from individual subjects manifested varying degrees of releasing ability but
      responded to different wines with a similar rank ordering. There was a high
      correlation (r = 0.87) between the effect of red wine and that of reserpine in
      different individuals. Some types of red wine caused a consistently higher
      release of 5-HT than others in all subjects; one red wine in particular resulted
      in negligible release. When several brands of this 'low-releasing' red wine were
      further examined, they all showed a lower activity than all the brands of a 'high
      releasing' red wine type. This variation in releasing power was not related to
      intensity of red colour. Partial purification of red wine was achieved by column
      chromatography and showed releasing activity to be associated with a low
      molecular weight orange fraction. Preliminary studies, using solid phase
      extraction methods, showed that the active components lie mainly in a subgroup of
      the flavonoid fraction. If any of the adverse effects of red wine, such as
      headache induction, derive from this 5-HT releasing ability, then it may be
      possible to prepare red wines free from the chemical substances responsible.

PMID- 7720791
TI  - Are NMDA or AMPA/kainate receptor antagonists more efficacious in the delayed
      treatment of excitotoxic neuronal injury?
AB  - At which time-point and to what extent do N-methyl-D-aspartate (NMDA) receptors,
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors
      and L-type voltage-sensitive Ca2+ channels (VSCC) contribute to glutamate-induced
      neuronal injury? To address this question, we induced glutamate neurotoxicity in
      two neuronal culture systems, chick telencephalic neurons and rat hippocampal
      neurons, and tested selective antagonists for their neuroprotective activity when
      administered either during the excitotoxic insult (acute treatment) or during the
      recovery period (posttreatment). In cultured chick telencephalic neurons exposed
      to 1 mM L-glutamate for 60 min, both the NMDA receptor antagonist dizocilpine (MK
      801; 0.1 microM) and the AMPA/kainate receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX; 1 microM) completely blocked glutamate-induced
      neuronal injury when applied concomitantly with glutamate. If the antagonists
      were applied during the recovery period, dizocilpine at concentrations up to 10
      microM only moderately increased cell viability, whereas CNQX showed a
      neuroprotective activity comparable to that observed in the case of the acute
      treatment. In cultured rat hippocampal neurons, excitotoxic injury was induced by
      a 30-min exposure to 1 microM glutamate. Treatment with dizocilpine during the
      glutamate exposure could rescue the hippocampal neurons from the excitotoxic
      insult, whereas acute treatment with the AMPA/kainate receptor antagonist 2,3
      dihydroxy-6-nitro-7-sulfamoylbenzo(F)-quinoxaline (NBQX) or the L-type VSCC
      blocker nimodipine showed no protection. In contrast, all three drugs showed
      neuroprotective activity when applied 30, 60 or 120 min after the glutamate
      exposure. Surprisingly, when the onset of the treatment was delayed for even 240
      min, only NBQX and nimodipine led to a reduction in excitotoxic neuronal injury.
      We conclude that activation of AMPA/kainate receptors and L-type VSCC is
      critically involved in a late stage of glutamate neurotoxicity, thereby allowing
      pharmacological intervention at a time when blockade of NMDA receptors becomes
      less efficacious.

PMID- 7720792
TI  - Tunicamycin potently inhibits tumor necrosis factor-induced hepatocyte apoptosis.
AB  - The protein glycosylation inhibitor tunicamycin protected male BALB/c mice from
      tumor necrosis factor alpha-induced liver failure. Tunicamycin also inhibited
      tumor necrosis factor-induced cell death in primary hepatocyte cultures with a
      median inhibitory concentration of 8 nM, but not in the tumor cell line WEHI 164
      clone 13. Hepatocyte death in our culture system was characterized by DNA
      fragmentation and apoptotic changes. These two characteristic signs of programmed
      cell death were also inhibited by tunicamycin treatment. These data suggest that
      protein glycosylation is an early and causal event of tumor necrosis factor (TNF)
      induced parenchymal cell death in the liver.

PMID- 7720793
TI  - Light maxillary expansion forces with the magnetic expansion device. A
      preliminary investigation.
AB  - An active maxillary magnetic expansion device (MED) was developed to be used
      clinically. The aim was to show the effects of light and continuous forces
      producing less traumatic stimulation of maxillary sutural growth than a
      conventional rapid maxillary expansion device. In this study, two different types
      of appliances were used on six patients between 7 years 4 months and 16 years 2
      months: the first type was bonded, the other one used bands. For better
      appreciation, four implants were placed on each patient: two apically between
      central and lateral incisors, and two between second premolars and molars. A
      standardized radiographic technique was used to take occlusal radiographs, and
      postero-anterior and lateral headplates. The results varied according to the age
      and the appliance used. The skeletal effect with the banded MED was between 16
      and 77 per cent, and for the bonded MED 0 and 25 per cent in comparison to the
      overall expansion. It seems that 250-500 g of continuous magnetic forces can
      produce dental and skeletal movements in a light force expansion concept, but
      further studies with larger samples are needed to make firm conclusions.

PMID- 7720794
TI  - Short-term consequences of orthognathic surgery on stomatognathic function.
AB  - Craniomandibular dysfunction, mandibular range of motion and occlusal contacts
      subsequent to surgical-orthodontic treatment were studied in 20 adults with Le
      Fort I impaction and/or advancement, 34 with vertical ramus setback, 12 with
      sagittal split advancement and 16 with Le Fort I impaction, and/or advancement
      and bilateral vertical ramus setback. All subjects were examined 1 week before
      surgery and 6 months post-operatively. The results of the study indicated that 6
      months post-operatively: (a) There was a decrease (NS) in dysfunction patients in
      the maxillary and double-jaw osteotomy groups, and an increase in the mandibular
      advancement osteotomy sample (P < 0.05). (b) There was a significant decrease in
      maximal interincisal opening in both mandibular osteotomy groups (P < 0.01) and
      in laterotrusive movements in the mandibular advancement group (P < 0.05). (c)
      The number and intensity of occlusal contacts increased significantly in the
      maxillary and mandibular setback osteotomy groups (P < 0.01 and P < 0.001,
      respectively).

PMID- 7720795
TI  - Longitudinal cephalometric standards for Norwegians between the ages of 6 and 18
      years.
AB  - The purpose of the present study was to develop normative cephalometric standards
      for Norwegians from 6 to 18 years of age. The subjects in the study included 39
      females and 35 males, from the Nittedal growth material. All subjects were
      Caucasians, and none had undergone orthodontic therapy, all had clinically
      acceptable normal occlusions and no apparent facial disharmony. Twenty-six
      measurements were analysed according to the cephalometric analysis used at the
      University of Oslo Department of Orthodontics. The measurements of posterior
      facial height, skeletal and soft tissue profiles were also included Comparisons
      between the dentofacial parameters of females and males at each age were
      performed using Student's t-test. Significant differences between females and
      males were present particularly at ages 12 and 15 years of age. There was a
      significant mean increase in NL/NSL in both sexes from 6 to 15 years of age, but
      more in females. There was a significant mean decrease in ML/NSL from 6 to 18
      years of age, and the angle was significantly smaller in males than in females.
      The anterior and posterior facial height increased in both sexes from 6 to 18
      years of age. The largest increase was in males. Males showed slightly more
      proclined upper incisors at age 9, 12, and 15 years than females. S-N-A increased
      more in males than females with the largest increase between 9 and 15 years of
      age. S-N-B increased in both sexes from 6 to 18 years of age with the largest
      increase in males.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720796
TI  - The monitoring of orthodontic tooth movement over a 2-year period by analysis of
      gingival crevicular fluid.
AB  - Gingival crevicular fluid (GCF) was collected from around canine teeth before
      orthodontic treatment, during retraction, and in retention. The aim was to
      investigate the changes in the flow of GCF and its glycosaminoglycan (GAG)
      components at these three stages of orthodontic treatment, and relate them to
      tooth movement, gingival inflammation, and other clinical parameters recorded at
      the time of GCF sampling. GAG in GCF samples, collected for a 15-minute period
      into microcapillary tubes, were separated and identified electrophoretically,
      stained with Alcian blue and quantitated using a laser densitometer. The increase
      in GCF volume during orthodontic tooth movement and the decrease during retention
      are only partly due to changes in the severity of gingival inflammation. Levels
      of the GAG component chondroitin sulphate found in GCF samples taken during
      retention appear to be related to the duration of retention, particularly the
      length of time that the fixed appliance is passive before debonding. GCF analysis
      may assist the clinician to conduct this phase of orthodontic retention more
      reliably.

PMID- 7720797
TI  - The role of occlusal discrepancies in the long-term stability of the mandibular
      arch.
AB  - To assess the influence of occlusal discrepancies on the long-term stability of
      orthodontic treatment, the dental casts, and cephalometric records of 40 patients
      were evaluated, pretreatment, post-treatment, and at least 9 years post
      retention. Post-treatment and post-retention casts were mounted in a semi
      adjustable articulator in RCP. In addition to arch dimension measurements,
      discrepancies between RCP and ICP were measured in three spatial planes using a
      condymeter. Arch width and length decreased significantly after retention. The
      position of the lower incisors was relatively stable, whereas the lower molars
      moved forward substantially. Lower anterior irregularity increased after
      treatment. As a consequence, 60% of the cases had unsatisfactory lower anterior
      alignment after retention. The long-term records generally showed a trend towards
      moderate crowding. The amount of slide decreased over time and had a
      statistically significant, though clinically only moderate, influence on the
      increase in lower anterior irregularity.

PMID- 7720798
TI  - Force system developed from closed coil springs.
AB  - The present paper provides data on load-deflection rate and maximal force
      generated for 19 coil springs. The force level at activation and deactivation was
      registered at intervals of 5 mm between 0 and 100 per cent extension. Ten springs
      of each type were analysed. The following questions were answered. How many of
      the springs exhibited the behaviour of a superelastic spring and how many types
      of springs differed significantly from each other with respect to force
      deflection rate and maximal force level at 100 per cent extension? Of the
      products tested only the springs from GAC exhibited the behaviour characteristic
      of the superelastic wire. The 19 products could, from a clinical point of view,
      be classified into four different groups with regard to force deflection rate and
      five groups with regard to maximal force. The variation within each product also
      differed between the products with the lowest intra-product variation seen in the
      TP springs. In light of the present findings it is obvious that manufacturers'
      information was not satisfactory. The need for more thorough user information is
      stressed.

PMID- 7720799
TI  - An evaluation of a light-curing composite for bracket placement.
AB  - In this study the clinical usefulness of a light-curing (Heliosit) and a
      chemically-curing composite (Concise) for orthodontic bracket bonding were
      compared. A sample of 37 patients to be treated with full Edgewise (FE) appliance
      in one or both arches (in total 52 dental arches) were randomly selected to have
      brackets on the left or right side of the dental arch bonded either with Concise
      or with Heliosit. In 12 patients, two teeth were extracted before orthodontic
      treatment and 25 patients were treated non-extraction. Impressions (Impregum) of
      the tooth surface and the bracket were made immediately after bracket loss.
      Frequency scores of bracket loss were noted for both composites and scanning
      microscopic evaluation of the tooth/composite surface was performed. Significant
      differences in bracket loss could be demonstrated between the two composites as a
      whole, and between the anterior and posterior parts of the dentition. For
      Heliosit bracket loss was observed predominantly in the posterior region, while
      for Concise it was distributed more equally over the dental arches. It was,
      however, demonstrated that in the clinical situation of bracket bonding the
      chemically-cured Concise failed significantly less than Heliosit in the overall
      frequency score.

PMID- 7720800
TI  - Localization of alpha-tubulin and carbonic anhydrase II mRNAs in isolated Muller
      cells.

PMID- 7720801
TI  - Light-evoked shedding in recombined eyecups from Xenopus laevis.

PMID- 7720802
TI  - Microscopical evaluation of the crystalline lens of the squid (Loligo opalescens)
      during embryonic development.
AB  - The similarity between the cephalopod lens and the teleost (vertebrate) lens can
      be considered an optical example of convergent evolution. However, the embryology
      and ultrastructure of the cephalopod lens appear to be different from that of
      vertebrates, and perhaps unique to the animal kingdom. Using light and scanning
      electron microscopy, the morphogenesis of the squid (Loligo opalescens) lens is
      characterized. Results indicate that the posterior lens primordium appears first
      during development and is derived from cellular processes which extend from a
      middle group, group 2, of lentigenic (ectodermal) cells. The processes extend
      from the basal aspect of the lentigenic cells, project down into the optic
      vesicle during early stages of development, and fuse to form the posterior lens
      primordium. During later stages, the processes extend from surrounding lentigenic
      cells and are applied to the stalk of the lens, where they form bud-shaped
      protrusions. Once applied to the lens, the processes form lens elements that
      later fuse into plate-like elements evident in later-staged embryo and adult
      lenses. The anterior lens primordium is derived from an anterior group, group 1,
      of lentigenic cells, during later stages of development. Lentigenic processes
      extend from these lentigenic cells and are laid down in a circumferential fashion
      to form the anterior lens cap. As in the posterior lens, evidence indicates that
      the anterior lens elements fuse to form plate-like elements. The ultrastructure
      and morphogenesis of the cephalopod lens is discussed and contrasted with other
      strategies of lens development.

PMID- 7720803
TI  - Two types of vasodilatation in cat choroid elicited by electrical stimulation of
      the short ciliary nerve.
AB  - Choroidal blood vessels are innervated by three types of vasoactive nerve fibers:
      sympathetic, parasympathetic and sensory fibers in the short ciliary nerve. We
      investigated whether or not stimulation of the short ciliary nerve elicits
      vasodilatation. In 30 cats (2-4 kg) anesthetized with pentobarbital sodium (30 mg
      kg-1, i.v.) and artificially ventilated (pancuronium bromide; 0.2 mg kg-1 hr-1,
      i.v.), choroidal blood flow was continuously measured trans-sclerally with a
      laser Doppler flowmeter. The lateral short ciliary nerve was stimulated
      electrically (0-50 V, 2 msec, 20 Hz, for 10 sec) at two sites, one close to the
      eyeball (site P) and the other between the main and accessory ciliary ganglia
      (site Q). Choroidal vasodilatation occurred with a high incidence (80%) in
      response to electrical stimulation of the short ciliary nerve at site P or Q,
      when cats had been treated with the alpha-adrenergic blocking agent phentolamine
      (3 mg kg-1) to eliminate sympathetic vasoconstrictor effects. A long-lasting
      vasodilatation was observed during 1% capsaicin application to the nerve bundle
      at site P, but not at site Q and capsaicin nearly abolished the vasodilatation
      evoked by stimulation at site P, but not that evoked from site Q. Vasodilatation
      elicited by electrical stimulation at site P or Q was not sensitive to the
      ganglion-blocking agent hexamethonium (3 mg kg-1, i.v.).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7720804
TI  - Regulation of cyclic AMP production in adult human ciliary processes.
AB  - Cyclic AMP production in intact ciliary processes from elderly human donors is
      subject to stimulatory and inhibitory control by various agents. Stimulation of
      cAMP production is observed with forskolin, vasoactive intestinal peptide, or the
      beta-adrenergic agonist isoproterenol. Inhibition of forskolin-stimulated cAMP
      production is observed with endothelin-2 or PAC. The inhibitory effect of PAC is
      blocked by the specific alpha 2-adrenergic antagonist, yohimbine. Endothelin-2
      has no effect on basal cAMP production. These data document the positive and
      negative regulation of cAMP responses in adult human ciliary processes and
      support the idea that cAMP is a key intermediate in the regulation of aqueous
      humor formation.

PMID- 7720805
TI  - Why does the human visual system age in the way it does?
AB  - The tentative observation that the decrease of lenticular glutathione in man and
      in cattle may be under genetic control is extended to other biological functions
      which show a systematic reduction with age. Ocular and visual parameters are
      shown to decline consistently with the view that the human eye has evolved in
      keeping with other biological functions sustaining a life-span of approximately
      120 years. Analysis of the data suggests that presbyopia represents an outlier in
      the distribution of ocular attributes, and should not be used as a biomarker for
      ageing.

PMID- 7720806
TI  - Isoprenoid lipid metabolism in the retina: dynamics of squalene and cholesterol
      incorporation and turnover in frog rod outer segment membranes.
AB  - Frogs were injected intravitreally with [3H]acetate, and the formation of [3H]
      labeled squalene and cholesterol in the retina and their incorporation into rod
      outer segment (ROS) membranes were evaluated biochemically over a 60-day time
      course. ROS [3H]squalene specific activity was maximal by 1-3 days, then declined
      with a half-time of approximately 20-30 days. In contrast, the specific activity
      of ROS [3H]cholesterol initially increased to a level substantially less than
      that of [3H]squalene, and then remained constant. Thus, ROS squalene appears to
      turn over without obligatory conversion to, or coturnover with, ROS cholesterol.
      When [3H]acetate was injected into one eye, radiolabel in non-saponifiable lipids
      of the contralateral retina represented < 1% of those recovered from the
      ipsilateral retina; hence, systemic contributions to de novo synthesis were
      obviated. Long-term (> or = 8 hr) in vitro incubations of isolated retinas with
      [3H]acetate resulted in incorporation of [3H]-labeled sterols and squalene into
      ROS, at levels comparable to those observed in ROS from companion incubated
      eyecup preparations and from retinas 8 hr after intravitreal injection of
      [3H]acetate. These results demonstrate that the in vitro system faithfully
      reflects the in vivo biosynthetic capacity with respect to isoprenoid lipid
      metabolism, and suggest that de novo synthesis within the neural retina is
      responsible for generating most, if not all, of the [3H]squalene and
      [3H]cholesterol formed under the given conditions. Treatment of retinas in vitro
      with brefeldin A or energy poisons blocked transport of newly synthesized opsin,
      but not squalene, to the ROS. Furthermore, frogs maintained at 8 degrees C
      exhibited marked suppression of incorporation of newly synthesized protein into
      the ROS, while [3H]squalene incorporation was only minimally reduced, compared
      with frogs maintained at 22 degrees C. These results are consistent with prior
      findings that suggest that lipids are transported to the ROS by a mechanism
      distinct and independent from that employed for intracellular trafficking of
      opsin and other ROS-destined membrane proteins.

PMID- 7720807
TI  - Histomorphometry of the optic nerves of normal dogs and dogs with hereditary
      glaucoma.
AB  - The beagle dog with hereditary primary open-angle glaucoma, unlike other animal
      models of human glaucoma, possesses a slowly progressive, sustained elevation of
      intraocular pressure. The effects of this insidious elevation in intraocular
      pressure on the axons of the optic nerves of three beagles at early stages of
      glaucoma and two beagles with advanced signs of glaucoma were compared to the
      optic nerves of four age-matched normal dogs. Plastic embedded optic nerve cross
      sections (1 micron) 1 mm posterior to the lamina cribrosa were osmicated and
      stained with Toluidine Blue. Axons from 0.2 to > 2.0 microns in diameter were
      counted and measured in 16 cross-sectional regions of equal size within the whole
      optic nerve using a computerized image analysis system. The mean optic nerve axon
      diameters in the normal, early glaucomatous, and advanced glaucomatous dogs were
      1.53, 1.25 and 1.13 microns respectively. The average total optic nerve axon
      count in the normal dogs was 148,303. Approximately 16% of the total axonal
      fibers were counted in each nerve. The counts of optic nerve axons 2.0 microns or
      greater in diameter were reduced by up to 60% in the central regions of the optic
      nerves of affected beagles. The large diameter axons of the peripheral optic
      nerve of the beagle dogs with glaucoma were more resistant to the elevated
      intraocular pressure. The counts of axons > 0.6 to 0.8 micron in diameter were
      significantly increased in glaucomatous beagles.

PMID- 7720808
TI  - Autoradiographic and biochemical assessment of rod outer segment renewal in the
      vitiligo (C57BL/6-mivit/mivit) mouse model of retinal degeneration.
AB  - Rod outer segment renewal was assessed in vitiligo (C57BL/6-mivit/mivit) mice
      using autoradiographic and biochemical methods. This process was examined because
      the number of phagosomes is reduced in this mouse. Rod outer segment renewal was
      detectable in the mivit/mivit retina. Within 24 hr of intraperitoneal injection
      of 3H leucine, there was a distinct band of radioactivity present at the junction
      of the ROS and RIS in mutant mice that was similar to controls. The displacement
      of the radioactive band progressed normally in the peripheral regions of the
      vitiligo retina, but did not in the posterior retina. Morphometric analysis of
      the posterior region of mutant retinas, indicated that the band of radioactivity
      became less distinct between 1 and 3 days post-injection. In vitiligo retinas it
      remained at 2.23 microns, whereas in controls, the band migrated 6.16 microns
      from the ROS base. When posterior regions of retinas were evaluated 8 days post
      injection, there was no band discernible in the vitiligo retinas, but a very
      dense band at the ROS apex in controls. Assessment of incorporation of
      radioactivity into rhodopsin using SDS-PAGE indicated a progressive displacement
      of radio-labeled rhodopsin through the RER, but not as complete a progression
      through the outer segments. The elongation of the outer segments in the posterior
      regions of the mutant retina suggests impaired shedding. This, plus the lack of
      attachment in the posterior retina of photoreceptor cells to RPE in this mouse,
      seem to be likely causes for the decreased number of phagosomes.

PMID- 7720809
TI  - Perspective on cataractogenic potential of HMG-CoA reductase inhibitors.

PMID- 7720810
TI  - In vivo models for studying the role of autocrine or paracrine growth factors in
      hematologic malignancies.

PMID- 7720811
TI  - Effects of rhIL-11 on normal dogs and after sublethal radiation.
AB  - The effects of recombinant human interleukin-11 (rhIL-11) were studied in normal
      dogs and dogs given otherwise sublethal total-body irradiation (TBI) without
      marrow transplantation. Ten normal dogs were given rhIL-11 subcutaneously, twice
      daily for 14 days at varying doses, two dogs at 30 micrograms/kg/day, four dogs
      at 60 micrograms/kg/day, two dogs at 120 micrograms/kg/day, and two dogs at 240
      micrograms/kg/day. Peripheral blood platelet counts increased in all dogs. The
      increase in platelet counts ranged from 1.4 to 3.1 times the pre-treatment level.
      The greater increases of platelets were associated with higher doses (p = 0.01).
      No change in platelet size was evident except at the dose of 240
      micrograms/kg/day. There were no changes in the total white blood cell (WBC)
      count or differential. A higher proportion of megakaryocytes with a DNA content
      of 32N/64N was observed in dogs treated with rhIL-11 at day 7 (n = 6) than for
      control dogs that did not receive rhIL-11 (n = 7; p = 0.01). In both peripheral
      blood and marrow, significantly increased hematopoietic progenitors (i.e, colony
      forming unit granulocyte/macrophage [CFU-GM]) were present 7 and 14 days after
      the start of treatment. Concentrations of serum fibrinogen increased by a median
      of 155 mg/dL at day 7 of rhIL-11 (p < 0.01). Cholesterol also increased by a
      median of 52 mg/dL at day 14 (p < 0.01). There was a single death of a non
      irradiated dog from pneumonitis on day 15 after the start of rhIL-11
      administration at a dose of 120 micrograms/kg/day. All other non-irradiated dogs
      tolerated rhIL-11 without any significant adverse effects. Five dogs were given
      200 cGy TBI without marrow grafting, followed by 240 micrograms/kg/day rhIL-11
      subcutaneously in two divided doses for 28 days starting within 2 hours of TBI.
      The results in this group were compared with 10 dogs that had previously or
      concurrently been given 200 cGy without marrow grafting or hematopoietic growth
      factors. Two of the five treatment dogs died of pneumonitis on day 13 compared to
      one death among 10 control dogs on day 24. Among dogs that survived to
      hematologic recovery, the rhIL-11 dogs had decreased platelet counts (< 150,000)
      for a median of 24 days (range = 24 to 41) compared to a median of 28 days (range
      = 21-40) for the control group. Treatment with rhIL-11 increased platelet counts,
      platelet size, ploidy number of megakaryocytes, and marrow and peripheral blood
      CFU-GM in normal dogs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7720812
TI  - rmIL-6 stimulates the transcriptional activity of the rat PF4 gene.
AB  - We have examined the effect of recombinant murine interleukin-6 (rmIL-6) on
      megakaryocytopoiesis in a liquid rat bone marrow culture system. At
      concentrations of IL-6 up to 100 ng/mL, no stimulation of megakaryocyte ploidy
      was observed. However, transient expression studies revealed that IL-6 did have a
      significant effect on the transcriptional activity of the platelet factor four
      (PF4) gene, a platelet alpha-granule protein gene uniquely expressed in
      megakaryocytes. Furthermore, when the amount of PF4 message was directly measured
      in megakaryocytes, it was increased three-fold in response to IL-6. We also note
      that the PF4 promoter contains a hexamer, CTGGGA, described as the IL-6
      responsive element in other genes. Our results suggest that the platelet progeny
      of IL-6-stimulated megakaryocytes may have altered alpha-granule constituents.

PMID- 7720813
TI  - Induction of apoptosis by iron deprivation in human leukemic CCRF-CEM cells.
AB  - It is known that iron is essential for cell growth and viability and that iron
      deprivation results in an inhibition in the synthesis of deoxyribonucleotides.
      However, steps leading to eventual cell death during iron deprivation are not
      fully understood. In the present study, we report that cellular iron-deficiency
      produced by exposure of human leukemic CCRF-CEM cells to gallium or the iron
      chelator deferoxamine (DFX) resulted in the inhibition of cell growth,
      condensation of chromatin, and the formation of DNA fragments (DNA-ladder),
      findings that are characteristic of apoptotic cell death. These effects of
      gallium and DFX were detected after a 48-hour incubation with cells and could be
      prevented by ferric ammonium citrate (FAC). Iron-deprivation produced a small
      increase in the endogenous expression of bcl-2 protein. Our studies provide
      additional information regarding the mechanism of cytotoxicity of gallium and
      DFX, and suggest, for the first time, a role for iron in the suppression of
      apoptotic cell death.

PMID- 7720814
TI  - Establishment of a CD4+ T cell clone recognizing autologous hematopoietic
      progenitor cells from a patient with immune-mediated aplastic anemia.
AB  - In some patients with aplastic anemia (AA), hematopoietic function is dependent
      on continuous administration of cyclosporine A (CyA). These AA patients may have
      T lymphocytes whose myelosuppressive effect is mitigated by CyA. We established a
      total of 29 T cell clones from the bone marrow of a CyA-dependent AA patient in
      relapse. Some of the CD4+ T cell clones demonstrated a specific proliferative
      response to irradiated autologous bone marrow cells enriched for CD34+ cells
      (CD34(+)-rich cells) obtained from the patient in remission. One of the T cell
      clones showing the best proliferative response to CD34(+)-rich cells carried the
      T cell receptor V beta 17 and produced interferon-gamma (IFN-gamma) only when
      cultured with autologous CD34(+)-rich cells. This T cell clone inhibited colony
      formation by colony-forming unit-granulocyte/macrophage (CFU-GM) and burst
      forming unit-erythroid (BFU-E) by approximately 60% when it was cultured with
      autologous CD34(+)-rich cells in methylcellulose medium, although the clone did
      not exhibit direct cytotoxicity to the CD34(+)-rich cells. The inhibition of in
      vitro hematopoietic progenitor cell growth by the T cell clone was partially
      abrogated by the addition of CyA to the culture. These findings suggest that in
      some patients with CyA-dependent AA, CD4+ T cells autoreactive to hematopoietic
      progenitor cells exist and may play an important role in the pathogenesis of bone
      marrow failure.

PMID- 7720815
TI  - Effect of methotrexate on murine bone marrow cells in vitro: evidence of a
      reversible antiproliferative action.
AB  - Methotrexate (MTX) acts by inducing cellular depletion of reduced folates, which
      ultimately leads to an inhibition of DNA synthesis. Like many anticancer drugs,
      this antimetabolite has little selectivity for tumor cells, and its effectiveness
      is limited by toxicity to normal tissues, particularly gastrointestinal
      epithelium and bone marrow. Previous studies have shown that MTX inhibits colony
      formation of the hematopoietic progenitor cells (CFU-C) in vitro. Whether this
      effect is due to a cytotoxic or a cytostatic mechanism has not been resolved. The
      present study was undertaken to eludicate the mechanism by which MTX inhibits CFU
      C formation. Bone marrow cells in agarose cultures supplemented with recombinant
      murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) were incubated
      for 7 days in the presence or absence of MTX. Exposure to 33 nM to 1 microM MTX
      reduced colony formation by more than 80% when compared to control cultures. When
      bone marrow suspension cultures supplemented with rmGM-CSF were incubated for 5
      days in the presence or absence of MTX, exposure to 10 nM to 1 microM MTX
      resulted in a 60 to 80% reduction in cell numbers when compared to untreated
      cultures. Residual CFU-C numbers were determined in the same cultures by
      replating into agarose. Exposure to 10 nM MTX was found to enhance CFU-C recovery
      three-fold as compared to controls and cultures exposed to higher MTX
      concentrations. Addition of 10 microM of the reduced folate leucovorin (LV; 5
      formyl-tetrahydrofolate) prevented CFU-C accumulation in the presence of 10 nM
      MTX. The kinetics of LV rescue of CFU-C, pre-exposed to 100 nM MTX, were
      investigated in clonogenic assays. The addition of 1 microM LV to semisolid bone
      marrow cultures preincubated with 100 nM MTX for up to 8 days completely
      abolished the inhibition of colony formation seen with 100 nM MTX alone. When the
      dose range of MTX was expanded from 33 nM to 3.3 microM, we found that
      administration of 10 microM LV on day 5 rescued the hematopoietic progenitors
      from MTX inhibition in all groups. These observations suggest that MTX is not
      cytotoxic to hematopoietic progenitors over its entire dose range but that it can
      induce a reversible block in the proliferation and differentiation of cells in
      the progenitor compartment.

PMID- 7720816
TI  - Enhanced elimination of Ph+ chromosome cells in vitro by combined hyperthermia
      and other drugs (AZT, IFN-alpha, TNF, and quercetin): its application to
      autologous bone marrow transplantation for CML.
AB  - Autologous bone marrow transplantation (ABMT) for chronic myelogenous leukemia
      (CML) is limited because of the difficulty in purging Ph chromosome positive
      cells from bone marrow cells (or peripheral blood stem cells). Combining
      hyperthermia with certain drugs that affect Ph+ cell growth in vivo and in vitro
      may enhance the killing (apoptosis) of CML cells in vitro. In this study, we
      chose such drugs (i.e., azidothymidine [AZT], interferon-alpha [IFN-alpha], tumor
      necrosis factor [TNF], and quercetin) and tested this hypothesis using two CML
      derived cell lines in vitro, K562 and KU812, to enhance the killing of CML cells
      with heat. Our results indicate that the optimal hyperthermic purging effect is
      achieved by heating at 42 degrees C for 1 hour with IFN-alpha (100 U/mL) and AZT
      (0.5 microM/L) or with quercetin (50 microM) [corrected], depending on the
      sensitivity of the CML cells eliminated in vitro. K562 cells were significantly
      eradicated by a combination of IFN-alpha and AZT, while KU812 cells were
      significantly inhibited by quercetin at the temperature and drug concentrations
      above. This combined effect may enhance apoptosis of CML cells in vitro.

PMID- 7720817
TI  - The cytokine receptor repertoire specifies autocrine growth factor production in
      factor-dependent cells.
AB  - Mechanisms of helper virus-induced growth factor-independence were examined in
      FDC-P1 cells and FDC-P1 cells expressing the erythropoietin receptor (FDER
      cells). Retroviral mutagenesis of FDC-P1 cells led to factor-independent (FI)
      colonies from which cell lines could readily be established; whereas control
      cells exhibited at least 20 to 40-fold lower rates of factor-independence. From
      44 independent experiments using either FDC-P1 or FDER cells, 205 autonomous cell
      lines were obtained. Sixteen colonies displayed a novel ("satellite-inducing")
      appearance in agar and produced up to 4.1 x 10(5) U/mL granulocyte-macrophage
      colony-stimulating factor (GM-CSF) (some with altered GM-CSF transcript sizes)
      and/or interleukin-3 (IL-3). Retroviral mutagenesis of FDER cells increased the
      repertoire of autocrine growth factors now responsible for stimulating autocrine
      proliferation: 3% of FI cell lines produced erythropoietin (Epo) (0.5 U/mL).
      Unexpectedly, in every autonomous FDC-P1 cell line, reverse transcriptase-PCR
      demonstrated expression of a growth factor normally required for proliferation.
      Thus, a profound selection for cells able to produce growth factors as the
      mechanism for achieving autonomous proliferation was documented. The ectopic
      expression of a receptor lacking a cognate ligand ("orphan") followed by
      retroviral mutagenesis and selection for autocrine mutants may offer an effective
      method for identifying new ligands.

PMID- 7720818
TI  - Effects of transferrin receptor antibody-NGF conjugate on young and aged septal
      transplants in oculo.
AB  - The purpose of this study was to investigate the effects of nerve growth factor
      (NGF) conjugated to a monoclonal transferrin receptor antibody (OX-26) on septal
      transplants in oculo. Three different doses of OX-26-NGF conjugate (0.3, 3, and
      50 micrograms/injection) were injected into the tail vein of young adult hosts 2,
      4, and 6 weeks following intraocular transplantation of fetal forebrain tissue
      containing septal nuclei. Intravenous injections of OX-26 alone, NGF alone, and
      saline served as controls. An increase in intraocular tissue growth, as well as
      an increase in the intensity of immunoreactivity for p75 receptors and
      acetylcholinesterase, was observed following peripheral OX-26-NGF administration
      at the two highest doses tested. In addition, aged host rats with 16-month-old
      intraocular septal grafts were injected intravenously with OX-26 or OX-26-NGF (10
      micrograms NGF/injection) every 2 weeks until the transplants were 24 months old.
      The intensity of choline acetyltransferase-like (ChAT) staining appeared to be
      greater and the cell bodies were larger with more processes in aged transplants
      in hosts treated with the OX-26-NGF conjugate than in aged OX-26-treated
      subjects. The present results suggest that peripheral OX-26-NGF can deliver
      biologically active NGF across the blood-brain barrier and have dose-dependent
      positive effects on both aged and developing cholinergic neurons in septal
      transplants.

PMID- 7720819
TI  - Specific lesions in the extrapyramidal system of the rat brain induced by 3
      nitropropionic acid (3-NPA).
AB  - The irreversible mitochondrial toxin 3-nitropropionic acid (3-NPA) is a specific
      inhibitor of succinate dehydrogenase. We performed stereotaxic unilateral
      injections of 3-NPA into the nigrostriatal dopaminergic pathway in rats in order
      to examine its specific effects on the dopamine system. The 3-NPA-treated rats
      displayed unidirectional apomorphineinduced rotations, suggesting that 3-NPA
      selectively damages dopaminergic neurons when injected into the nigrostriatal
      pathway. In situ hybridization 7 weeks postinjection indicated a decrease in
      tyrosine hydroxylase (TH) mRNA to 30% of the noninjected side in the substantia
      nigra pars compacta (P < 0.05) and decreased to 62% of the noninjected side in
      the ventral tegmental area (VTA) (nonsignificant) of 3-NPA-lesioned rats. The
      number of TH mRNA positive cells showed statistically significant decreases in
      substantia nigra and VTA (P < 0.001) within the lesioned side. In contrast,
      expression of mRNAs encoding choline acetyltransferase, p75 low-affinity NGF
      receptor, neurotrophin tyrosine kinase receptors Trk and TrkB, and brain-derived
      neurotrophic factor showed neuronal sparing in several other regions of the
      brain. The results suggest that the nigrostriatal dopaminergic system might be
      selectively vulnerable to 3-NPA and demonstrate that it is possible to employ 3
      NPA in a model of partial lesion of the nigrostriatal dopaminergic system
      resembling early stages of Parkinson's disease.

PMID- 7720820
TI  - Prevention of hypoxic-ischemic damage with dexamethasone is dependent on age and
      not influenced by fasting.
AB  - Pretreatment with the synthetic glucocorticoid dexamethasone prevents hypoxic
      ischemic brain damage in 7-day-old neonatal rats. We presently characterize the
      response further by examining the effect of varying the age, the glucocorticoid,
      and the time of injection and by examining whether fasting can influence the
      response. Rats (n = 193) were randomized to one of 16 different treatment groups
      and subjected to hypoxia-ischemia (right carotid artery occlusion +8% O2 which
      was 3 h in duration for 7-day, 1 h for 2-week, and 30 min for 1-month-old
      animals). The brains were subsequently perfusion fixed and the area of infarction
      was measured from hematoxylin- and eosin-stained sections. Time dependence
      studies demonstrated that treatment with 0.1 mg/kg intraperitoneal dexamethasone
      4 h prior to hypoxia reduced infarct size compared to vehicle-treated animals
      whereas pretreatment at either 48 h or 4 days was ineffective. Dexamethasone
      pretreatment (4 h) also provided neuroprotection against 4 h of hypoxia-ischemia.
      Fasted animals which received dexamethasone had reduced blood glucose levels yet
      markedly less damage than controls. Another glucocorticoid, methylprednisolone
      (0.7 mg/kg), also reduced infarction. In 2-week-old animals the area of
      infarction was reduced by pretreatment with dexamethasone, whereas in 1-month-old
      animals dexamethasone was ineffective. The results suggest that a glucocorticoid
      mediated response intervenes in events leading to neuronal death in young animals
      but not older animals once myelination and synaptogenesis are complete.

PMID- 7720821
TI  - gp120, an HIV-1 protein, increases susceptibility to hypoglycemic and ischemic
      brain injury in perinatal rats.
AB  - Recent data suggest that gp120, a glycoprotein secreted by HIV-1-infected
      macrophages, is neurotoxic, and that toxicity is mediated, at least in part, by
      overactivation of NMDA-type excitatory amino acid receptors. In experimental
      animals, considerable evidence indicates that hypoglycemic and ischemic neuronal
      injury are mediated by endogenous excitatory amino acids. We hypothesized that in
      the presence of gp120 the severity of brain injury resulting from hypoglycemia
      and cerebral ischemia would increase. To test this hypothesis in vivo, we
      evaluated the influence of gp120 on the extent of brain injury resulting from
      these two clinically relevant pathophysiological insults in 7-day-old (P7) rats,
      the developmental stage of peak susceptibility to NMDA neurotoxicity. We compared
      the severity of hippocampal injury resulting from right intrahippocampal
      injections of gp120 (50 ng) in P7 rats rendered markedly hypoglycemic (n = 10)
      and in controls (n = 12). We also determined the influence of gp120
      administration on the severity of hypoxic-ischemic injury, using a perinatal rat
      stroke model. P7 rats received intrahippocampal injections of gp120 (50 ng) (n =
      23) or saline (n = 18) and then underwent right carotid ligation, followed by 2 h
      exposure to 8% oxygen. Brain injury was evaluated 5 days later, based on
      neuropathology evaluation and measurements of bilateral regional cross-sectional
      areas. The severity of hippocampal injury, based on cross-sectional area
      measurements, was considerably greater in animals from the hypoglycemic group
      than in litter-mate gp120-injected controls. Among the animals that underwent
      hypoxic-ischemic lesioning, the severity of injury, based on histopathology
      scoring and regional volume measurements, was considerably greater in animals
      that received gp120 than in those that received saline. These results provide
      support for the hypothesis that locally secreted HIV peptides, such as gp120, may
      potentiate the neurotoxicity of endogenous excitatory amino acid
      neurotransmitters in HIV-infected brain.

PMID- 7720822
TI  - CNS distribution and overexpression of neurofilament light proteins (NF-L) in
      mice transgenic for the human NF-L: aberrant accumulation in thalamic perikarya.
AB  - Light microscopic immunocytochemistry with monoclonal antibodies recognizing both
      murine and human light neurofilament proteins (mNF-L and hNF-L) or hNF-L only was
      used to examine the distribution of NF-L in the CNS of adult mice, normal or
      transgenic for the human gene. In normal mice, major fiber bundles were
      immunoreactive to the first antibody, with few exceptions such as the internal
      capsule, anterior commissure, and corpus callosum. Strong immunoreactivity was
      also present in the perikarya of motoneurons in the spinal cord and brainstem, as
      well as in other brainstem nuclei. Faint cell body staining was visible in layers
      II, III, and V of the parietal cortex and layers V and VI of the retrosplenial
      cingulate cortex. In transgenic mice, all forebrain as well as brainstem fiber
      tracts were intensely immunoreactive to both antibodies. Cell body staining was
      more intense than in normal mouse and involved additional forebrain and brainstem
      regions, including extended areas of cerebral cortex. Abnormal cell body labeling
      was particularly striking in several thalamic nuclei, where numerous darkly
      stained perikarya were considerably enlarged by accumulated immunoreactive
      material and exhibited eccentric and fragmented nuclei. At the electron
      microscopic level, these perikarya were filled with disarrayed filaments
      displacing all other organelles against the cytoplasmic membrane. Such aberrant
      accumulation of NF-L was presumably the result of an overexpression in selective
      subpopulations of CNS neurons. It was compatible with prolonged survival of the
      animal and could provide a new experimental model of neurodegenerative disease.

PMID- 7720823
TI  - Correlation between NGF levels in wound chamber fluid and cytological
      localization of NGF and NGF receptor in axotomized rat sciatic nerve.
AB  - When a silicone tube is implanted in transected rat sciatic nerve, there is
      plasma accumulation and formation of a fibrin cable followed by proliferation and
      migration of neural and nonneural cells from the nerve stumps into the cable. The
      wound fluid exhibited neurotrophic activity of unknown origin and nature. In this
      study, we analyzed the NGF level in wound fluid by a sensitive enzyme immunoassay
      and correlated the NGF level with the cytological localization of NGF, low
      affinity NGF receptor (p75NGFR), and Trk receptor in the axotomized nerve by
      immunohistochemistry. We demonstrated a rising NGF level in wound fluid from 490
      pg/ml on Day 1 to 950 pg/ml on Day 7; the serum NGF level was 1/20 of that in the
      wound fluid. The infiltrating leukocytes expressed strong NGF but no p75NGFR. The
      proliferative fibroblasts and vascular cells exhibited a short period of NGF but
      no p75NGFR staining. Schwann cells in the distal segment showed a prolonged
      period of NGF and p75NGFR expression. No Trk receptor was demonstrated on
      leukocytes or non-neural cells. These findings suggest that locally synthesized
      NGF is mainly responsible for the neurotrophic activity in the wound chamber
      fluid. The NGF produced by the nonneural cells may be bound and stored in the
      p75NGFR in Schwann cells in the distal segment prior to the arrival of the
      regenerating axons.

PMID- 7720824
TI  - Induction of nerve growth factor and basic fibroblast growth factor mRNA
      following clenbuterol: contrasting anatomical and cellular localization.
AB  - RNase protection assay and in situ hybridization were used to analyze the
      temporal and cellular changes in nerve growth factor (NGF) and basic fibroblast
      growth factor (bFGF) mRNA content evoked by the lipophilic beta-adrenergic
      receptor agonist clenbuterol in adult rat brain. Clenbuterol elicited a threefold
      increase in NGF mRNA expression which was limited to the cerebral cortex. This
      increase was maximal at 5 h, still evident by 10 h, and declined to control
      levels by 24 h. By 10 h NGF protein was also increased. Elevated NGF mRNA
      hybridization following clenbuterol was localized in the superficial cortical
      layers II and III in large Nissl-pale cells, suggesting that NGF mRNA induction
      occurs in neurons. In the same animals, clenbuterol induced a twofold increase in
      the levels of bFGF mRNA in cerebral cortex and hippocampus. This increase was
      localized primarily in glial cells as demonstrated by bFGF mRNA hybridization
      over all cortical regions and by labeling of the stratum lacunosum moleculare of
      the hippocampus. Our results suggest that enhanced noradrenergic tone regulates
      expression of these two trophic factors by different synaptic mechanisms and
      suggest that neurotransmitter(s) can coordinate trophic influences on different
      cell populations.

PMID- 7720825
TI  - Particulate forms of APP in the extracellular milieu of cultured cells.
AB  - The principle externalized forms of amyloid precursor protein (APP) are soluble
      and well-characterized, but some evidence has suggested the additional presence
      of externalized APP in a nonsoluble form. To further assess this possibility, the
      current study has applied high resolution microscopy protocols in addition to
      immunoprecipitation to characterize externalized APP in three commonly used cell
      culture models (SH-SY5Y human neuroblastoma cells, fetal rat brain cells, and HEK
      293 human embryonic kidney cells). Confocal immunofluorescence microscopy, using
      an antiserum against the c-terminal domain of APP, showed typical cell-associated
      APP, but hot spots of APP also were evident in cell-free areas, apparently
      associated with the culture substrata. These hot-spots were examined for evidence
      of cellular deterioration by whole mount transmission electron microscopy.
      Neither cell debris nor disrupted cells were present. Instead, the hot spots of
      substratum-bound APP comprised discrete microparticles, approximately 50-100 nm
      across. These microparticles also could be found near cells and in some cases
      were attached to cell surface fibrils. Substratum-bound APP also could be found
      clustered within the extracellular matrix made by primary cell cultures.
      Occurrence of APP in extracellular microparticles was verified by centrifugation
      immunoprecipitation analysis of media conditioned by APP-transfected cells.
      Radiolabeling data showed that particulate APP was from metabolically active
      cells. Metabolic labeling of particle-associated APP, as well as the absence of
      cellular debris near the APP-containing particles, suggests that the occurrence
      of nonsoluble APP in the extracellular milieu derives from a physiologically
      active process.

PMID- 7720826
TI  - Protection from oxidation enhances the survival of cultured mesencephalic
      neurons.
AB  - Oxidative stress has been linked to the destruction of dopaminergic neurons in
      the substantia nigra and may be a significant factor in both Parkinson's disease
      and MPTP toxicity. Using primary cultures of embryonic rat mesencephalon and
      standard immunocytochemical techniques, we have examined the survival of tyrosine
      hydroxylase-containing (TH+) neurons cultured in the presence of antioxidants
      and/or in an environment of low oxygen partial pressure. The number of TH+
      neurons increased approximately twofold if superoxide dismutase, glutathione
      peroxidase (GP), or N-acetyl cysteine (NAC) were added to the culture media.
      Exposure of the neurons to a 5% oxygen environment (38 torr, i.e., 38 mm Hg) also
      increased the survival of TH+ neurons by about twofold. A dramatic enhancement of
      survival, however, was seen when NAC was used in combination with the 5% oxygen
      environment. In this case, the number of TH+ neurons increased fourfold from
      nontreated controls. Morphological changes were also noted. GP increased the
      average neurite length while NAC increased the average area of the cell body in
      the TH+ neuron. These results suggest that manipulation of oxidative conditions
      by changing the ambient O2 tension or the level of antioxidants promotes survival
      of TH+ neurons in culture and may have implications for transplantation therapies
      in Parkinson's disease.

PMID- 7720827
TI  - Implantation of encapsulated catecholamine and GDNF-producing cells in rats with
      unilateral dopamine depletions and parkinsonian symptoms.
AB  - Studies in rodents suggest that PC12 cells, encapsulated in semipermeable
      ultrafiltration membranes and implanted in the striatum, have some potential
      efficacy for the treatment of age- and 6-OHD-induced sensorimotor impairments
      (22, 70, 71, 74). The objectives of this study were to: (1) determine if baby
      hamster kidney cells engineered to secrete glial cell line-derived neurotrophic
      factor (BHK-GDNF) would survive encapsulation and implantation in a dopamine
      depleted rodent striatum, (2) compare polymer-encapsulated PC12 and PC12A cells
      in terms of their ability to survive and produce catecholamines in vivo in a
      dopamine-depleted striatum, and (3) determine if BHK-GDNF, PC12, or PC12A cells
      reduce parkinsonian symptoms in a rodent model of Parkinson's disease. Capsules
      with BHK-GDNF or PC12 cells contained viable cells after 90 days in vivo, with
      little evidence of host tissue damage/gliosis. In rats with tyrosine hydroxylase
      (TH)-positive fibers remaining in the lesioned striatum, there was TH-positive
      fiber ingrowth into the membranes of the BHK-GDNF capsules. PC12-containing
      capsules had higher basal release of both dopamine and L-DOPA after 90 days in
      vivo than before implantation, while basal release of both dopamine and L-DOPA
      decreased in the PC12A-containing capsules. Both encapsulated PC12 and PC12A
      cells, but not encapsulated BHK-GDNF cells, decreased apomorphine-induced
      rotations. Parkinsonian symptoms (akinesia, freezing/bracing, sensorimotor
      neglect) related to the extent of dopamine depletion were evident even in rats
      with dopamine depletions of only 25%. Evidence that encapsulated cells may
      attenuate these parkinsonian symptoms was not detected but most of the rats were
      more severely depleted of dopamine than Parkinson's patients (less than 2%
      dopamine remaining in the entire striatum), and these tests were not sensitive to
      differences between rats with less than 10% dopamine remaining. These results
      suggest that cell encapsulation technology can safely provide site-specific
      delivery of dopaminergic agonists or growth factors within the CNS, without
      requiring suppression of the immune system, and without using fetal tissue. Of
      the three types of encapsulated cells examined in the present study, PC12 cells
      seem to offer the most therapeutic potential in rats with severe dopamine
      depletions.

PMID- 7720828
TI  - Loss of viable neuronal units in the proximal stump as possible cause for poor
      function recovery following nerve reconstructions.
AB  - Function recovery after nerve reconstructions is often poor. Could this be caused
      by a loss of viable neuronal units proximal to the nerve reconstruction? The
      number of neuronal units (i.e., a motor or sensory neuron, including its axon and
      axonal branches) in the proximal segments of reconstructed peripheral nerves were
      studied using a novel magnetic recording technique. In five rabbits a common
      personal nerve was transected and microsurgically reconstructed. After 8 weeks
      regeneration time the nerve compound action signals were recorded magnetically
      from the reconstructed as well as from the healthy contralateral peroneal nerve
      and from peroneal nerves of five unoperated control animals. The amplitudes of
      the recorded signals were compared and the diameter distribution histograms were
      calculated. These calculations were based on the conduction distance between the
      stimulator and the sensor and the conduction velocities of 30 different axon
      diameter classes ranging from 3 to 18 microns. Our results indicate that there is
      a reduction of approximately 50% in the number of viable neuronal units at 10 mm
      proximal to a simple nerve reconstruction after 8 weeks regeneration time. The
      number of neuronal units innervating a hand is strongly correlated with clinical
      function in a healthy hand. The reduction in viable neuronal units after a
      reconstruction, demonstrated in our experiments, corresponds with a frequently
      clinically observed decrease in function after nerve reconstructions. Therefore,
      we suggest that the number of viable neuronal units may be a good indicator of
      final functional recovery.

PMID- 7720829
TI  - Immunosuppressive effect of 15-deoxyspergualin applied to peripheral nerve
      allotransplantation in the rat.
AB  - 15-Deoxyspergualin (15-DSG), which has a unique immunosuppressive action, was
      applied to peripheral nerve allotransplantation. Its effects on graft survival
      were experimentally assessed using inbred rats. The sciatic nerve (20 mm)
      allotransplantation model was created in two different strains. An attempt was
      made to answer the following two questions: (1) can short-term immunosuppression
      alone produce sufficient immunological tolerance to maintain graft survival
      indefinitely? (2) can graft rejection be prevented by chronic intermittent low
      dose 15-DSG administration (2.5 mg/kg/day), and to what extent does nerve
      regeneration occur? To evaluate the efficacy of 15-DSG, a comparison was made
      with autografts, allografts with no immunosuppression, and allografts
      immunosuppressed with cyclosporine (CsA), a strong immunosuppressant. The results
      indicate that short-term 15-DSG therapy is incapable of inducing immunotolerance
      of peripheral nerve allografts. Because nerve conduction in the rejected
      allografts was better preserved than in the CsA group, short-course 15-DSG
      therapy appeared to provide better results than CsA therapy for peripheral nerve
      allotransplantation.

PMID- 7720830
TI  - Ethanol withdrawal induces increased firing in inferior colliculus neurons
      associated with audiogenic seizure susceptibility.
AB  - Ethanol withdrawal (ETX) in ethanol-dependent rats results in susceptibility to
      seizures, including generalized tonic-clonic audiogenic seizures (AGS). The
      inferior colliculus (IC) is strongly implicated in AGS initiation during ETX, but
      IC neuronal mechanisms subserving AGS are unclear. The present study examined IC
      (central nucleus) single neuronal firing during repeated (4 day) intragastric
      ethanol administration and during ETX. This involved microwire electrodes
      implanted chronically into freely moving rats and acoustic stimulation in
      intensities up to 105 dB SPL. During initial ethanol administration the animals
      were stuporous, and IC spontaneous neuronal firing and acoustically evoked firing
      at high stimulus intensities were significantly reduced. This firing reduction is
      consistent with the action of ethanol to enhance gamma-aminobutyric acid (GABA)
      mediated inhibition, which is prominent in IC neurons at high stimulus
      intensities. During ETX the animals were agitated, and spontaneous IC neuronal
      firing and acoustically evoked firing at all stimulus intensities were
      significantly increased during the period of AGS susceptibility. Previous studies
      indicate that IC neuronal responses are tightly regulated by GABA and glutamate.
      The IC firing increases during ETX in the present study may involve the down
      regulation of GABAA receptors and supersensitivity of glutamate receptors
      reported to occur during ETX. Previous studies also indicate that focal blockade
      of GABAA receptors or activation of glutamate receptors produces AGS
      susceptibility in normal rats. Therefore, the IC neuronal firing increases
      observed in the present study may play a critical role in initiation of AGS
      during ethanol withdrawal.

PMID- 7720831
TI  - Functional evaluation of regenerated and misrouted axons to glabrous and hairy
      skin of the rat hind foot after sciatic neurotomy and suture.
AB  - The function of misrouted regenerated polymodal nociceptor C-fibers and low
      threshold mechanoreceptive axons in the lateral plantar nerve (LPN) and in the
      foot branch of the superficial peroneal nerve (fSPN) was evaluated 3 months after
      unilateral sciatic neurotomy and suture. Two weeks before evaluation the tibial
      fascicle (or the peroneal fascicle) above the neurotomy was cut and tied off. In
      this way only functional regeneration of misrouted axons was tested in the LPN
      (or the fSPN). In regenerated animals the glabrous skin area had no functional
      fSPN-related low-threshold mechanoreceptive axons. However, the hairy fSPN skin
      area showed function of misrouted LPN-related low-threshold mechanoreceptive
      axons. In both the glabrous skin domain innervated by the LPN and the hairy skin
      area supplied by the fSPN, functional regeneration of misrouted polymodal
      nociceptor C-fibers was found. We conclude that functional regeneration of
      misrouted axons related to polymodal nociceptive units and low-threshold
      mechanoreceptive units is more efficient in hairy skin of the rat foot whereas
      only misrouted polymodal nociceptor C-fibers recover function in glabrous skin.

PMID- 7720832
TI  - Prognostic relevance of a histologic classification system applied in bone marrow
      biopsies from patients with multiple myeloma: a histopathological evaluation of
      biopsies from 153 untreated patients.
AB  - A total of 153 diagnostic bone marrow biopsies from patients with advanced stages
      of multiple myeloma corresponding to stages II and III according to the
      Durie/Salmon classification were evaluated prior to any treatment in a
      prospective therapy trial of the German Myeloma Treatment Group. Histologic
      sections were analyzed according to a pre-defined system of criteria
      microscopically by 2 observers, determining three criteria: 1) grading by
      histopathology, regarding the cytologic differentiation of neoplastic cells and
      quantifying the percentage of plasmacytic, pleomorphic, and plasmablastic myeloma
      cells distributed within the sections; 2) the volume of infiltration; and 3) the
      pattern of neoplastic growth. Furthermore, four other criteria, namely
      hematopoiesis, fiber increase, osteomalacia, and micro-osteo-lesions, were
      evaluated. A cluster analysis using the three histological criteria revealed
      three groups of patients with significantly different survival times based on
      histological criteria only; the three criteria were mentioned above. It is
      concluded from these results that bone marrow biopsies, when evaluated
      histologically by grading and staging according to the three criteria, provide
      most valuable prognostic parameters in myeloma patients.

PMID- 7720833
TI  - Effects of monocyte-macrophage colony-stimulating factor (M-CSF) on in vitro
      erythropoiesis of marrow progenitor cells from patients with renal anemia.
AB  - We examined the influence of monocyte-macrophage colony-stimulating factor (M
      CSF) on erythropoiesis both in vitro and in vivo in 98 patients with chronic
      renal failure who were undergoing hemodialysis. Serum levels of M-CSF and the
      clinical response to therapy with human recombinant erythropoietin (Epo) were
      analyzed. The following results were obtained: 1) The serum level of M-CSF was
      6.90 +/- 2.41 ng/ml in the patient population (n = 98), but only 2.0 +/- 0.3
      ng/ml in 10 healthy donors. 2) 41 of the 98 anemic patients were treated with
      various doses of Epo for 3 months, and the average increase in the blood
      hemoglobin level during this period was 26.1 +/- 12.5 mg/dl/unit of Epo/kg
      patient's b.w./week. Lower levels of M-CSF before treatment significantly
      predicted a better response to subsequent Epo therapy (r = -0.496, p < 0.001). 3)
      When cultured with a maximally stimulatory amount of Epo (10 IU/ml), the number
      of marrow early erythroid progenitor cells (burst-forming unit for erythroid, BFU
      E) in patients was identical to that in normal donors, while the number of late
      progenitors (colony-forming unit for erythroid, CFU-E) was relatively lower in
      patients. 4) The addition of recombinant M-CSF to the culture resulted in
      suppression of erythroid progenitor cell growth in the patient population, but
      induced enhancement in normal donors. The inhibitory effect of M-CSF on the
      patients' cells was not eliminated by the addition of antibodies against
      interleukin-1 alpha/beta, tumor necrosis factor-alpha, or interferon
      alpha/beta/gamma. Supernatants from marrow mononuclear cells cultured in the
      presence of M-CSF carried this inhibitory effect on marrow CD34+ cells obtained
      from patients. Together, these results suggest that M-CSF aggravates a previously
      existing decreased sensitivity of erythroid progenitor cells to Epo in some
      patients with renal anemia.

PMID- 7720834
TI  - Incidence of myelodysplastic syndromes in a Swedish population.
AB  - The myelodysplastic syndromes (MDS) have attracted great interest during the last
      decade. Unfortunately there is not much material published concerning the
      incidence of these conditions. We present epidemiologic data on MDS based on case
      registration of patients in a well-defined population and as a comparison similar
      data on acute myeloid leukaemia (AML). Between the years 1978-1992 we registered
      120 cases of MDS and 146 cases of AML. The median age for all the MDS cases was
      74.1 years for men and 78.2 years for women. Among haematologists there is a
      suspicion that the incidence of MDS is rising. Our study does not support this
      opinion. We have divided the study period into 5-year periods and the crude
      incidence has been 3.2, 4.1 and 3.5/100,000/year for each period. In the age
      group over 70 years MDS was more frequent than AML and in the last 5-year period
      the incidence was 15.0/100,000/year for MDS compared to 10.2/100,000/year for
      AML. In conclusion MDS is quite common among elderly people and there is no
      evidence for a rising incidence during the last 15 years.

PMID- 7720835
TI  - Pulmonary infiltrates in patients with haematologic malignancies: clinical
      usefulness of non-invasive bronchoscopic procedures.
AB  - In a prospective study 90 patients with haematologic malignancies (57 acute
      leukaemias, 6 Hodgkin's Diseases, 15 Non-Hodgkin Lymphomas, 12 other diseases),
      with fever exceeding 38.4 degrees C and newly developed pulmonary infiltrates
      underwent bronchoscopy obtaining bronchoalveolar lavage, bronchial washings and
      protected brush specimen (n = 71). Pneumonias due to gram-negative bacteria (n =
      38) and fungi (n = 34) were most frequent. Bronchoscopic specimens yielded 226
      isolates (2 different organisms/bronchoscopy on average). 112 organisms were
      finally regarded as causing pneumonia. Sensitivity of bronchoscopy in diagnosing
      infectious episodes was 66%, but only 4 out of 13 non-infectious pulmonary
      infiltrates could be identified. Bronchoscopy was most effective in the diagnosis
      of pneumocystis carinii and herpes virus pneumonia, whereas sensitivity and
      specificity of detecting fungal and bacterial pneumonia were low. Empirical
      antimicrobial therapy was verified by evaluation of bronchoscopic samples in 25
      out of 90 cases. Empirical therapy was successfully changed according to the
      results of invasive samplings in 34 out of 90 cases. Early identification of
      causative pathogens had a significant impact on survival.

PMID- 7720836
TI  - Automated measurement of reticulated platelets in estimating thrombopoiesis.
AB  - We described a fully automated measurement of reticulated platelets using a
      fluorescent dye, auramine O, and a reticulocyte counter, the R-3000, equipped
      with special software. Reproducibility and linearity were shown to be good. In
      the normal subjects studied (n = 60), the mean value for reticulated platelets
      was 0.98% +/- 0.41% and the mean absolute count was 2.12 +/- 0.69 x 10(9)/l. The
      absolute count for reticulated platelets was significantly lower (p < 0.05) in
      patients with reduced thrombopoiesis as seen in acute myeloblastic leukemia,
      aplastic anemia or chemotherapy-induced thrombocytopenia and it was elevated (p <
      0.05) in essential thrombocythemia and in chronic myelocytic leukemia with
      thrombocytosis. All 20 patients with chronic idiopathic thrombocytopenic purpura
      had a high percentage of reticulated platelets. The percentage of reticulated
      platelets was significantly increased (p < 0.05) in patients with impaired
      thrombopoiesis despite the reduction in the absolute count. In 2 leukemic
      patients, an apparent rise was noticed in the percentage of reticulated platelets
      which preceded by several days a progressive increase in the platelet count at
      the recovery phase of thrombocytopenia. The results suggest that an automated
      measurement of reticulated platelets can be applied to routine laboratories for
      clinical use.

PMID- 7720837
TI  - Synergism of interleukin-12 and interleukin-3 on development of hematopoietic
      progenitors.
AB  - The recently cloned cytotoxic lymphocyte maturation factor [CLMF] also called NK
      cell stimulatory factor [NKSF] or interleukin-12 [IL-12] has been described as a
      growth factor for mature lymphoid cells. The present study investigated whether
      purified recombinant human IL-12 could stimulate CFU colony growth. Source of
      progenitor cells were peripheral blood cells depleted of adherent, CD2- and CD56
      positive cells. RhIL-12 was investigated either alone or in combination with rhIL
      3, rhIL-6 and rhGM-CSF. RhIL-12 alone did not support colony formation of myeloid
      or erythroid progenitors. RhIL-12 in combination with rhIL-3 increased the
      numbers of BFU-E and CFU-GM. No synergism or additive effect was seen with the
      combination of rhIL-12 and rhGM-CSF or rhIL-12 and rhIL-6. An additive increase
      in the number of granulocytic colonies was observed when rhIL-3, rhIL-6 and rhGM
      CSF were used together with rhIL-12. Our results therefore suggest that, in
      addition to being a potent lymphopoietic stimulator, IL-12 acts synergistically
      with IL-3 in enhancing the sensitivity of hemopoietic progenitors to IL-3.

PMID- 7720838
TI  - Haemostatic and fibrinolytic parameters in septic patients with leukopenia or
      leukocytosis.
AB  - Induction of leukocytopenia by cytotoxic drugs protects against the generalized
      Shwartzman reaction induced by endotoxin. To elucidate the relationship between
      leukocyte number and in haemostatic and fibrinolytic disturbances in human
      sepsis, we studied 32 septic patients with abnormal leukocyte counts. Twenty
      patients had sepsis in the setting of leukopenia after chemotherapy for
      haematological malignancies. Twelve patients with leukocytosis developed sepsis
      associated with benign disorders. Concentrations of thrombin-antithrombin III
      complex (TAT), plasminogen activator inhibitor-1 (PAI-1) and plasma
      thrombomodulin (TM) in the leukocytosis group of (12.0 +/- 11.0, 40.2 +/- 27.0
      and 5.5 +/- 2.3 ng/ml, respectively) were significantly elevated compared to the
      leukopenia group of (3.8 +/- 2.3, 18.0 +/- 15.0 and 3.1 +/- 1.0 ng/ml,
      respectively) and controls (3.3 +/- 0.4, 10.5 +/- 5.3, 3.0 +/- 0.5 ng/ml,
      respectively). On the other hand, there were no significant differences in these
      values between leukopenia group and controls. Thus leucocytes may play important
      roles in thrombin generation, PAI-1 release and injury to endothelial cells.

PMID- 7720839
TI  - Deep venous thrombosis and pulmonary artery embolism in high-grade non Hodgkin's
      lymphoma: incidence, causes and prognostic relevance.
AB  - To analyse incidence, risk factors, causes and prognostic significance of venous
      thromboembolism (VTE) in high-grade non-Hodgkin's lymphoma (HG-NHL) a prospective
      clinical trial (N = 593), also undertaken to analyse other aspects of HG-NHL, a
      study of haemostasis (N = 25) and a post-mortem analysis (N = 70) were performed.
      Clinical analysis documented a 6.6% incidence of VTE, and 77% of all cases
      occurred before or within the first 3 months of chemotherapy. Ann Arbor stage IV
      and B-mediastinal clear cell histology were risk factors for VTE, while rapid
      changes in tumour load or application of consolidation chemotherapy were not.
      Vessel compression by HG-NHL was the leading cause of VTE, whereas a significant
      (paraneoplastic or chemotherapy-induced) thrombophilic state was not disclosed by
      haemostatic tests. While VTE-related fatality was found to be low in the clinical
      trial (1.7%) and at necropsy (8.5%), the occurrence of VTE was associated with an
      unsatisfactory response of HG-NHL to chemotherapy and a high incidence of
      treatment-related mortality due to diffuse alveolitis. Thus, fatal VTE in HG-NHL
      is rare, but VTE is associated with an unfavourable clinical course of HG-NHL.

PMID- 7720840
TI  - The in vivo erythropoiesis of patients with polycythaemia vera is insensitive to
      stimulation with recombinant human erythropoietin.

PMID- 7720841
TI  - Possible role of macrophage-colony stimulating factor in the development of
      hemophagocytic syndrome.

PMID- 7720842
TI  - Donor cell leukaemia--an unresolved problem.

PMID- 7720843
TI  - The determination of plasma transferrin receptor (TfR) in patients with heart
      valve prosthesis: a useful evaluation of bone-marrow response to traumatic
      haemolysis.

PMID- 7720844
TI  - Biological diagnosis of a gamma-1-heavy chain disease in an asymptomatic patient.

PMID- 7720845
TI  - Intestinal mycobacteriosis in a patient with acute myeloid leukaemia after
      autologous peripheral blood stem cell transplantation.

PMID- 7720846
TI  - Can the hemophiliac bleed less?

PMID- 7720847
TI  - Intention status of U.S. births in 1988: differences by mothers' socioeconomic
      and demographic characteristics.
AB  - The National Maternal and Infant Health Survey provides new data on the
      prevalence of unintended childbearing in the United States: Thirty-six percent of
      births in 1988 were mistimed and 7% were unwanted, while 57% were intended.
      Although the level of unintended childbearing is high in almost all socioeconomic
      subgroups of women, the proportion of births that were mistimed or unwanted was
      50% or more among age-groups 15-17 (78%), 18-19 (68%) and 20-24 (50%), and among
      never-married women (73%), formerly married women (62%), black women (66%), women
      living below the federal poverty level (64%) or at 100-149% of the poverty level
      (52%), women with less than 12 years of education (58%) and women who already had
      two children (53%) or three or more children (60%). Multivariate analyses
      indicate that births to unmarried women--whether formerly married or never
      married--are less likely than those to married women to be wanted and more likely
      to be mistimed. Poverty status has no independent effect on the odds that a birth
      is unwanted or on the odds that a birth to an unmarried woman is mistimed. Among
      currently married women, those who are poorer are more likely than women above
      150% of the poverty level to have a mistimed birth. Black women are more likely
      than either Hispanic or white women to report a birth as unwanted and are more
      likely than white women to say a wanted birth was mistimed.

PMID- 7720848
TI  - The relationship of substance use to sexual activity among young adults in the
      United States.
AB  - Data on substance use and sexual activity from a nationally representative,
      probability-based sample of young adults aged 18-30 in 1990 indicate that 86% of
      respondents had had sex in the previous 12 months, with three-fourths reporting
      no more than one sexual partner. Seventy-five percent of respondents had consumed
      alcohol in the past 12 months, 40% had smoked cigarettes and 20% had used
      marijuana. After adjustment for demographic factors, both sexual activity and a
      history of multiple partners were positively associated with some measures of
      substance use. Respondents who drank more frequently, those who were heavy
      drinkers, those who smoked cigarettes and those who used marijuana in the past
      year were more likely than others to be sexually active. Those who consumed five
      or more drinks at a sitting and those who used marijuana were more likely than
      others to have had more than one sexual partner. Heavy drinkers were also less
      likely to use condoms; however, the results showed no association between having
      sex under the influence of alcohol and engaging in unsafe sexual practices.

PMID- 7720849
TI  - Adolescent fertility and the educational attainment of young women.
AB  - Analyses based on a sample of 2,795 women interviewed annually from 1979 through
      1991 in the National Longitudinal Survey of Youth show that early childbearing
      lowers the educational attainment of young women. After controls for an extensive
      set of personal and community characteristics are taken into account, having a
      child before age 20 significantly reduces schooling attained by almost three
      years among whites, blacks and Hispanics. Having a child before age 18 has a
      significant effect only among blacks, reducing years of schooling by 1.2 years.

PMID- 7720850
TI  - Predictors of condom acquisition after an STD clinic visit.
AB  - Data from a survey of 691 men and women who made patient visits to an inner-city,
      sexually transmitted disease (STD) clinic and were given coupons to redeem for
      condoms at a neighborhood pharmacy show that only 22% of the sample did so.
      Gender, ethnicity, marital status and education were not significant predictors
      of whether study participants redeemed their coupons. Factors that significantly
      predicted coupon redemption included the extent of acculturation and age, with
      those who were older and less acculturated more likely to do so. Other
      significant factors were having a primary sexual partner and having had more than
      one sexual partner in the last month; having ever had an STD was negatively
      associated with coupon redemption. A perception of being at high STD risk and a
      favorable attitude about condoms also significantly predicted condom acquisition.
      All these variables, except for attitude toward condoms and a history of an STD,
      remained significant when entered into a logistic regression controlling for the
      influence of all independently significant predictors.

PMID- 7720851
TI  - The contraceptive implant and the injectable: a comparison of costs.
AB  - A comparison of the relative costs of the injectable contraceptive (depot
      medroxyprogesterone acetate) and the hormonal implant (Norplant) indicates that
      the implant is a less costly contraceptive option when it is used for its full
      five-year lifespan. Over a five-year period, the implant costs $107 annually,
      compared with $140 per year for the injectable. However, if a woman discontinues
      the implant before she has used it for at least four years, the injectable
      becomes the less costly option. Relatively high continuation rates--around 95%
      annually--are necessary to make the implant the more cost-effective contraceptive
      method.

PMID- 7720852
TI  - A longitudinal comparison of the AIDS-related attitudes and knowledge of parents
      and their children.
AB  - As part of an evaluation of an experimental school-based AIDS risk-reduction
      program, data from 2,392 middle-school students in 15 high-risk school districts
      and from 1,627 of their parents were compared to examine how young adolescents
      and their parents differ with respect to AIDs-related knowledge and attitudes. At
      the time of the seventh-grade pretest, parents knew significantly more about AIDS
      than their children did. At the eighth-grade posttest, students who participated
      in the program knew either more than or at least as much as their parents in
      several subject areas, while among those not exposed to the program, parents
      still knew more than their children in most areas. The intervention had a
      positive impact on students' attitudes toward people with AIDS and on their
      degree of comfort about discussing with their parents such issues as drug use and
      sexuality.

PMID- 7720853
TI  - Purification of the hepatic glycogen-associated form of protein phosphatase-1 by
      microcystin-Sepharose affinity chromatography.
AB  - The form of protein phosphatase-1 associated with hepatic glycogen (PP1G) was
      purified to near homogeneity from rat liver by affinity chromatography on
      microcystin-Sepharose and gel-filtration. The enzyme is a heterodimer consisting
      of the catalytic subunit of PP1 (the alpha and beta isoforms) complexed to a 33
      kDa glycogen-binding (GL) subunit. The GL subunit binds phosphorylase a with high
      affinity, and is responsible for the enhanced dephosphorylation of glycogen
      synthase by PP1G and its allosteric inhibition by phosphorylase a.

PMID- 7720854
TI  - The endozepine ODN stimulates polyphosphoinositide metabolism in rat astrocytes.
AB  - Astrocytes synthesize a series of peptides called endozepines which act as
      endogenous ligands of benzodiazepine receptors. The present study demonstrates
      that the endozepine ODN causes a dose-dependent increase in inositol
      trisphosphate and a parallel decrease in phosphatidylinositol bisphosphate in
      cultured rat astrocytes. Pre-incubation of astrocytes with the phospholipase C
      inhibitor U 73122 or with pertussis toxin totally blocked polyphosphoinositide
      metabolism. These data show that, in rat astrocytes, ODN stimulates a
      phospholipase C coupled to a pertussis toxin-sensitive G protein.

PMID- 7720855
TI  - In vitro binding of Bacillus thuringiensis var. israelensis individual toxins to
      midgut cells of Anopheles gambiae larvae (Diptera: Culicidae).
AB  - Midguts from Anopheles gambiae fourth instars were dissected and processed for
      immuno-light microscopy. Cloned insecticidal crystal proteins (ICPs) from
      Bacillus thuringiensis var. israelensis (Bti) were individually expressed in
      crystal-negative strains of Bacillus thuringiensis. Tissue sections of A. gambiae
      were incubated in vitro with each solubilized and trypsin-activated ICP.
      Immunodetection of CryIVA, CryIVB, CryIVD and CytA toxins on sections was
      performed using purified rabbit IgG directed against Bti ICPs, in combination
      with an anti-rabbit IgG/peroxidase. CryIVA, CryIVB, CryIVD and CytA toxins were
      detected on the apical brush border of midgut cells, in the gastric caecae and
      posterior stomach. CytA was also detected, to a lesser extent, on microvilli of
      anterior stomach cells.

PMID- 7720856
TI  - DNA replication specificity of TYLCV geminivirus is mediated by the amino
      terminal 116 amino acids of the Rep protein.
AB  - Geminiviruses are plant DNA viruses replicating by a rolling circle mechanism. We
      have investigated the specificity of replication origin recognition of two
      different isolates of tomato yellow leaf curl virus (TYLCV). Here, we show that
      TYLCV-Sardinian and -Israeli replication proteins display a high degree of
      specificity for their respective origins. The DNA sequences recognized are
      located on the left part of the intergenic region whereas the amino-terminal 116
      amino acids of the Rep protein determine the specificity of origin recognition.

PMID- 7720857
TI  - Equatorial split of holo-chaperonin from Thermus thermophilus by ATP and K+.
AB  - Holo-chaperonin molecule from Thermus thermophilus is a bullet-shaped particle
      whose cylinder part and round top are composed of two stacked rings of the cpn60
      heptamer and a single ring of the cpn10 heptamer, respectively. We found that it
      splits at the plane between two cpn60 rings into two halves under physiological
      conditions, that is, in the presence of ATP (but not AMP-PNP, ADP) + K+ (but not
      Na+) at 60 degrees C. This equatorial split could be functionally important
      although it has not been considered in any current mechanistic model of
      chaperonin functioning.

PMID- 7720858
TI  - The Sec61 complex is essential for the insertion of proteins into the membrane of
      the endoplasmic reticulum.
AB  - Cross-linking studies have implicated Sec61 alpha as the principal component
      adjacent to newly synthesised membrane proteins during insertion into the
      endoplasmic reticulum. Using proteoliposomes which have been reconstituted from
      purified components of the endoplasmic reticulum [Gorlich, D and Rapoport, T.A.,
      Cell 75 (1993) 615-630] we have found that the Sec61 complex, consisting of three
      subunits, is essential for the insertion of single-spanning membrane proteins.
      This is true for signal-anchor proteins of both orientations, and for proteins
      with a cleavable signal sequence. These results support the view that Sec61 alpha
      is a major component of the ER translocation site and promotes both the insertion
      of membrane proteins and the translocation of secretory proteins.

PMID- 7720859
TI  - A primordial dopamine D1-like adenylyl cyclase-linked receptor from Drosophila
      melanogaster displaying poor affinity for benzazepines.
AB  - We report here the isolation from Drosophila melanogaster of a 2.0 kb cDNA clone
      encoding a 385 amino acid protein (dDA1) displaying, within putative
      transmembrane domains, highest amino acid sequence homology (49-53%) to members
      of the vertebrate dopamine D1-like receptor family. When expressed in either Sf9
      or COS-7 cells, dDA1 did not bind the specific D1-like receptor antagonist
      [3H]SCH-23390 or numerous other dopaminergic, adrenergic or serotoninergic
      ligands with high affinity. However, like vertebrate dopamine D1-like receptors,
      dDA1 stimulated the accumulation of cAMP in response to DA (EC50 approximately
      300 nM) and 6,7-ADTN (EC50 approximately 500 nM). The dopaminergic rank order of
      potency (DA > NE >> 5-HT) and the lack of stimulation by other possible
      neurotransmitters (octopamine, tyramine, tryptamine) or DA metabolites (e.g. N
      acetyl dopamine) found in Drosophila suggests that this receptor functionally
      belongs to the dopamine D1-like subfamily. Benzazepines, which characteristically
      bind to vertebrate dopamine D1-like receptors with high affinity, were relatively
      poor in stimulating (SKF-38393, SKF-82526; EC50 > 10 microM) dDA1-mediated
      accumulation of cAMP. Of the numerous compounds tested, a few dopaminergic
      antagonists inhibited DA-stimulated production of cAMP in a concentration
      dependent manner, albeit with considerably reduced affinity, and with the rank
      order of potency: (+)-butaclamol(Kb approximately 125nM) > SCH-23390(Kb
      approximately 230nM) > alpha-flupenthixol (Kb approximately 400 nM) >
      chlorpromazine > or = spiperone (Kb approximately 680 nM) > or = clozapine. In
      situ hybridization revealed that dDA1 receptor mRNA is expressed as a maternal
      transcript, and at later blastoderm stages is restricted to apical regions of the
      cortical peripheral cytoplasm. The generation of inter-species D1 receptor
      chimeras may help to identify those particular sequence-specific motifs or amino
      acid residues conferring high affinity benzaepine receptor interactions.

PMID- 7720860
TI  - Comparative proteolytic processing of rat prosomatostatin by the convertases PC1,
      PC2, furin, PACE4 and PC5 in constitutive and regulated secretory pathways.
AB  - Recombinant vaccinia virus vectors were used to coexpress each of the candidate
      prohormone convertases PC1, PC2, furin, PACE4 and PC5 with rat prosomatostatin
      (rProSOM) in the constitutive secreting cell line LoVo and in the endocrine
      corticotroph cell line AtT-20, which exhibits regulated secretion. Mammalian
      ProSOM is cleaved at a dibasic Arg-Lys decreases site to produce somatostatin-14
      (S-14) and at a monobasic Gln-Arg decreases site to yield somatostatin-28 (S-28).
      The analysis of processed products by gel-permeation high performance liquid
      chromatography shows that in LoVo cells PC1, furin and PACE4 generate S-14, S-28
      and a mixture of S-14 and S-28, respectively, while PC2 is unable to process
      ProSOM in these constitutive cells. In contrast, PC2 can generate S-14 in AtT-20
      cells. The convertase PC5 is unable to process ProSOM in either cell line. These
      data suggest that PC2, PC1 and PACE4 are candidate S-14 convertases, while PACE4
      and furin are candidate S-28 convertases.

PMID- 7720861
TI  - Regulation and localization of midkine in rat ovary.
AB  - In a previous experiment, it was shown that midkine (MK) was quite abundant in
      the follicular fluid; the concentration of MK in bovine follicular fluid was
      estimated to be 125 micrograms/l. To investigate the regulation of MK production
      in the ovary, we examined the effect of pregnant mare's serum gonadotropin (PMSG)
      and PMSG-hCG treatment on the expression of MK in rat ovary. The mRNA of midkine
      (MK) was increased by PMSG injection and decreased by PMSG and hCG injection; the
      profile of change of mRNA of MK was similar to that of FSH receptor. Using in
      situ hybridization, we observed that the MK mRNA localized to granulosa cells.
      These results suggest that the granulosa cells produce MK under the control of
      gonadotropin.

PMID- 7720862
TI  - Structure-function studies on the biosynthesis and bioactivity of the precursor
      convertase PC2 and the formation of the PC2/7B2 complex.
AB  - Site directed mutagenesis of the prohormone convertase PC2 was used to define the
      effect of certain residues on the zymogen activation of proPC2 and on its binding
      to the neuroendocrine protein 7B2. These included the oxyanion hole Asp309
      (D309N), the N-terminal Glu25 (E25Q and E25K) of proPC2 and the Asp519 (D519E) of
      the RGD motif within the P-domain of PC2. Heterologous vaccinia virus expression
      of the wild type and mutant PC2's in endocrine pituitary cells such as AtT20 and
      GH3 cells demonstrated that the most dramatic effect was observed with the D309N
      mutant which no longer bound pro7B2 and which exhibited a significant reduction
      in its capacity to produce beta-endorphin from pro-opiomelanocortin (POMC).

PMID- 7720863
TI  - Improved measurement of 13C, 31P J coupling constants in isotopically labeled
      RNA.
AB  - 3JCP coupling constants have been measured in a 99% 13C,15N labeled lead
      dependent ribozyme, known as the leadzyme. These coupling constants were
      determined by analysis of the intensity of individual crosspeaks in a spin-echo
      difference constant time HSQC experiment. This procedure permits improved
      measurement of the 3JC2'P and 3JC4'P coupling constants in isotopically labeled
      RNA and yielded valuable information on the beta and epsilon backbone torsion
      angles in the leadzyme.

PMID- 7720864
TI  - Deficiency of ganglioside biosynthesis in metastatic human melanoma cells:
      relevance of CMP-NeuAc:LacCer alpha 2-3 sialyltransferase (GM3 synthase).
AB  - The glycosphingolipid patterns were analyzed on two clones derived from a human
      melanoma cell line and selected for their respectively high and low metastatic
      ability in immunosuppressed newborn rats. Conversely to the weakly metastatic
      cells which exhibited a pattern similar to that of the parental cell line, highly
      metastatic human melanoma cells appeared to be deficient in ganglioside
      biosynthesis. An accumulation of lactosylceramide was found in the latter cells,
      with low amounts of GM3 as the only ganglioside detected and a fourfold decreased
      activity of GM3 synthase (EC 2.4.99.9). After subcutaneous injection of
      metastatic cells in newborn rats, the cells proliferating in the tumor induced at
      the injection site re-expressed the four common gangliosides of melanoma: GM3,
      GM2, GD3 and GD2, whereas the cells growing in the lungs as metastatic nodules
      were deficient in ganglioside synthesis and showed an accumulation of
      lactosylceramide. Taken together, our results suggest that the human melanoma
      cells which are able to escape from the primary tumor and invade the lungs have
      an impaired ganglioside biosynthesis with a deficient GM3 synthase.

PMID- 7720865
TI  - Iron release, membrane protein oxidation and erythrocyte ageing.
AB  - The aerobic incubation of erythrocytes in phosphate buffer for 24-60 h (a model
      of rapid in vitro ageing) induced progressive iron release and methemoglobin
      formation. Membrane proteins showed electrophoretic alterations and increase in
      carbonyl groups (as documented by IR spectroscopy). None of these phenomena were
      seen when the erythrocytes were incubated under anaerobic conditions. The
      membranes from aerobically incubated cells bound a much higher amount of
      autologous IgG than those from anaerobically incubated ones, suggesting that the
      aerobic incubation gives rise to the senescent antigen. The addition of ferrozine
      during the aerobic incubation prevented both the IgG binding and the protein
      alterations seen in the IR spectra, suggesting an intracellular chelation of the
      released iron by ferrozine.

PMID- 7720866
TI  - Reassembly of Synechocystis sp. PCC 6803 F1-ATPase from its over-expressed
      subunits.
AB  - Subunits alpha, beta, and gamma of the F1-part of cyanobacterial F0F1-ATPase have
      been cloned into expression vectors. Over-expressed subunit beta was found
      soluble in the cytoplasmic fraction of Escherichia coli cells under appropriate
      culture and induction conditions and was purified from cell extracts. Recombinant
      alpha and gamma subunits precipitated into inclusion bodies and had to be
      solubilized, purified and refolded. The correct folding and functional integrity
      of the alpha and beta subunits was monitored by their ability to bind
      nucleotides. Active cyanobacterial F1-ATPase was assembled from its purified
      subunits alpha, beta, gamma, delta and epsilon. The reassembled enzyme
      reconstituted ATP synthesis in F1-depleted thylakoid membranes of Synechocystis
      sp. PCC 6803 and hydrolyzed ATP.

PMID- 7720867
TI  - Properties of N-terminus truncated and C-terminus mutated muscle
      acylphosphatases.
AB  - Enzymatic activity and structure of N-terminus truncated and C-terminus
      substituted muscle acylphosphatase mutants were investigated by kinetic studies
      under different conditions and 1H NMR spectroscopy, respectively. The N-terminus
      truncated mutant lacked the first six residues (delta 6), whereas arginine 97 and
      tyrosine 98 were replaced by glutamine giving two C-terminus substituted mutants
      (R97Q and Y98Q, respectively). All acylphosphatase forms were obtained by
      modifications of a synthetic gene coding for the human muscle enzyme which was
      expressed in E. coli. The delta 6 deletion mutant elicited a reduced specific
      activity and a native-like structure. The kinetic and structural properties of
      R97Q and Y98Q mutants indicate a possible role of Arg-97 in the stabilisation of
      the active site correct conformation, most likely via back-bone and side chain
      interactions with Arg-23, the residue involved in phosphate binding by the
      enzyme. This study also suggests a possible involvement of Tyr-98 in the
      stabilisation of the acylphosphatase overall structure.

PMID- 7720868
TI  - Sucrose: a solute that accumulates in the guard-cell apoplast and guard-cell
      symplast of open stomata.
AB  - Stomatal conductances of Vicia faba leaves were recorded over a day.
      Coordinately, (a) guard cells dissected from leaflets were assayed, providing
      total sucrose content, and (b) guard cells dissected from rinsed epidermes were
      also assayed, providing symplastic sucrose content. Compared with that of pre
      dawn samples, apoplastic sucrose content increased 4.8-5.2 x (2 experiments),
      reaching 1,130-1,300 fmol.guard-cell-pair-1 at midday, when conductance was
      highest (ca. 0.13 mol.m-2.s-1); symplastic sucrose content increased 2.5-3.5 x,
      reaching 350-390 fmol.guard-cell-pair-1. Thus, there is a correlation between
      transpiration and guard-cell sucrose content, particularly that portion localized
      to the apoplast. Moreover, apoplastic sucrose is apparently a source of guard
      cell nutrition and, possibly, osmoticum.

PMID- 7720869
TI  - Synthetic phosphopeptide from rhodopsin sequence induces retinal arrestin binding
      to photoactivated unphosphorylated rhodopsin.
AB  - A synthetic heptaphosphopeptide comprising the fully phosphorylated carboxyl
      terminal phosphorylation region of bovine rhodopsin, residues 330-348, was found
      to induce a conformational change in bovine arrestin. This caused an alteration
      of the pattern of limited proteolysis of arrestin similar to that induced by
      binding phosphorylated rhodopsin or heparin. Unlike heparin, the phosphopeptide
      also induced light-activated binding of arrestin to both unphosphorylated
      rhodopsin in disk membranes as well as to endoproteinase Asp-N-treated rhodopsin
      (des 330-348). These findings suggest that one function of phosphorylation of
      rhodopsin is to activate arrestin which can then bind to other regions of the
      surface of the photoactivated rhodopsin.

PMID- 7720870
TI  - Observation of the pre-steady state process in thermolysin catalysis with a
      fluorescent displacement probe at low pH.
AB  - The pre-steady state process in the thermolysin-catalyzed hydrolysis of Cbz-Gly
      Phe-Ala was observed at pH 4.5 by fluorescence stopped-flow method using Dns-Phe
      as a displacement probe. After the confirmation of the pre-equilibrium hypothesis
      for the binary interaction, the nonlinear substrate concentration dependence of
      the apparent kinetic constant for the pre-steady state process was analyzed and
      an existence of multi-intermediates was proposed.

PMID- 7720871
TI  - SR 120819A, an orally-active and selective neuropeptide Y Y1 receptor antagonist.
AB  - An orally-active antagonist of neuropeptide Y (NPY) Y1 receptors, SR 120819A, has
      been characterized. This compound displays highly selective and competitive
      affinity for rat, guinea-pig and human (Ki = 15 nM) NPY Y1 receptors. In vitro,
      SR 120819A blocks the inhibitory effect of NPY on adenylyl cyclase activity in
      human SK-N-MC cells and that of the selective Y1 agonist, [Leu31,Pro34]NPY, on
      rabbit vas deferens contraction (pA2 = 7.20 +/- 0.07). In vivo, by intravenous
      route, this compound acts as an antagonist in anesthetized guinea-pigs and,
      notably, after oral administration, SR 120819A counteracts the pressor response
      of [Leu31,Pro34]NPY (5 micrograms/kg i.v.) with a long duration of action (> 4 h
      at 5 mg/kg p.o.). Thus, SR 120819A is the first orally-effective NPY Y1 receptor
      antagonist yet described. It could be a useful tool for exploring the role of NPY
      and the therapeutic relevance of an antagonist at NPY Y1 receptors.

PMID- 7720872
TI  - Enhanced susceptibility of cholesteryl sulfate-enriched low density lipoproteins
      to copper-mediated oxidation.
AB  - Cholesteryl sulfate (CS) is a minor component of cell membranes, also present in
      lipoproteins, and its exact function is unknown. Since oxidation of low density
      lipoproteins (LDL) is thought to be an important determinant of atherogenesis, we
      investigated the influence of CS enrichment on copper-mediated oxidation of LDL.
      CS was found to act as a pro-oxidant, as measured by lipid oxidation parameters.
      The results also suggest that these effects were dependent on the sulfate group
      since pure cholesterol or cholesteryl acetate did not promote Cu(2+)-mediated
      oxidation. Our findings imply that CS may affect the oxidizability and hence the
      potential atherogenicity of LDL.

PMID- 7720873
TI  - Sequence specificity for removal of uracil from U.A pairs and U.G mismatches by
      uracil-DNA glycosylase from Escherichia coli, and correlation with mutational
      hotspots.
AB  - The rate of removal of uracil from different positions in double-stranded DNA by
      uracil-DNA glycosylase from Escherichia coli varied more than 15-fold. Consensus
      sequences for good and poor removal were 5'-(A/T)UA(A/T)-3' and 5'-(G/C)U(T/G/C)
      3', respectively. In general, the sequence context surrounding U was more
      important for the rate of removal than whether U was present in U.A pairs or U.G
      mispairs. Rates of removal of U from sites of amber mutations in the lacI gene,
      where mutation frequencies and deamination rates were known, indicated that the
      observed variation in removal is biologically significant.

PMID- 7720874
TI  - Functional analysis of a newly identified TAAT-box of the rat insulin-II gene
      promoter.
AB  - Transcriptional regulation of insulin gene expression is achieved by an interplay
      of tissue-specific and ubiquitous cis- and trans-acting elements. E-box like
      motifs and TAAT-motifs were shown to play a crucial role in initiating insulin
      gene transcription. Studying the AT-rich region of the rat insulin-II promoter
      between nucleotides -212 and -196, we observed a base difference at -211, an
      adenosine instead of a cytidine, compared to the previously reported sequence
      (EMBL Accession No. J00748). Sequence analysis of promoter fragments from
      different rat strains showed that adenosine at position -211 represents the wild
      type (EMBL Accession No. X82162). This base exchange leads to the formation of an
      additional TAAT-motif, i.e. TAAT3, at the complementary DNA strand directly
      upstream of the previously studied TAAT2 motif, formerly named CT-2. Here we show
      that the newly identified motif TAAT3 is involved in (i) transcriptional control
      in vivo, (ii) in vitro DNA/protein interactions, and that (iii) TAAT1, TAAT2 and
      TAAT3 are binding sites for the homeodomain-containing factor IPF-1.

PMID- 7720875
TI  - Studies on the promoter of the Arabidopsis thaliana cdc2a gene.
AB  - The 5' flanking (promoter) region of the Arabidopsis thaliana cdc2a gene was
      cloned and sequenced. A number of putative regulatory motifs were identified
      including one Myc and three Myb protein binding sequences plus one abscisic acid
      and two auxin responsive elements. One of the three Myb protein binding sequences
      is positioned within an auxRE. Promoter-GUS fusions were introduced into plants
      to study the role of two promoter regions in regulating gene expression. Absence
      of one Myb binding sequence and the auxRE containing a Myb binding sequence
      resulted in a significant reduction in expression levels as did a deletion
      involving the Myc and the third Myb binding sequences along with the second
      auxRE. However, no changes in expression patterns were observed. The results were
      quantified using transgenic root cultures.

PMID- 7720876
TI  - Hepatocyte growth factor remains as an inactive single chain after partial
      hepatectomy or unilateral nephrectomy.
AB  - Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and renal
      tubular epithelial cells. HGF is proteolytically activated in the tissue injured
      by hepatotoxin or nephrotoxin, suggesting that HGF functions as a crucial growth
      factor for tissue regeneration following hepatotoxin- or nephrotoxin-induced
      injury. In this study, we analyzed the molecular form of HGF after partial
      hepatectomy or after unilateral nephrectomy. The active form of HGF was not
      detected under our experimental conditions after these operations. Thus, HGF may
      play little role in liver regeneration after partial hepatectomy and in
      compensatory renal enlargement after unilateral nephrectomy.

PMID- 7720877
TI  - Retardation by the soybean Bowman-Birk inhibitor of elastin hydrolysis catalyzed
      by leukocyte proteinases.
AB  - The classical Bowman-Birk inhibitor from soya retards strongly the hydrolysis of
      elastin catalyzed by leukocyte elastase, cathepsin G and a mixture of both. The
      inhibitory effect is practically unaffected by both the adsorption of the enzymes
      on elastin and prolongation of the enzymatic reaction.

PMID- 7720878
TI  - The essential yeast NLT1 gene encodes the 64 kDa glycoprotein subunit of the
      oligosaccharyl transferase.
AB  - The yeast oligosaccharyl transferase catalyzes the glycosylation of asparagine
      residues in secreted, vesicular, and membrane proteins. A complex of at least
      four membrane-bound polypeptides is responsible for oligosaccharyl transferase
      activity. Amino acid sequences from the 64 kDa glycoprotein subunit of the
      complex were used to clone the essential NLT1 (N-linked oligosaccharyl
      transferase) gene. The Nlt1p gene product is a processed, multiply glycosylated
      type I membrane protein; it has an extensive amino-terminal soluble domain, a
      potential hydrophobic transmembrane domain, and a short carboxy-terminal soluble
      domain. The Nlt1p is significantly similar than the mammalian ribophorin I, a
      component of the mammalian oligosaccharyl transferase complex, and the enzyme is
      conserved throughout eukaryotic evolution.

PMID- 7720879
TI  - Destruction of photosystem I iron-sulfur centers in leaves of Cucumis sativus L.
      by weak illumination at chilling temperatures.
AB  - The activity of photosystem (PS) I in cucumber leaves was selectively inhibited
      by weak illumination at chilling temperatures with almost no loss of P-700
      content and PSII activity. The sites of inactivation in the reducing side of PSI
      were determined by EPR and flash photolysis. Measurement by EPR showed the
      destruction of iron-sulfur centers, FX, FA and FB, in parallel with the loss of
      quantum yield of electron transfer from diaminodurene to NADP+. Flash photolysis
      showed the increases in the triplet states of P-700 and antenna pigments, along
      with the decrease in the electron transfer from P-700 to FA/FB. This indicates
      the increase in the charge recombination between P-700+ and A0-. It is concluded
      that weak-light treatment of cucumber leaves at chilling temperature destroys FX,
      FA and FB and possibly A1. This gives the molecular basis for the mechanism of
      selective PSI photodamage that was recently reported [Sonoike and Terashima
      (1994) Planta 194, 287-293].

PMID- 7720880
TI  - Liposome destabilization induced by the HIV-1 fusion peptide effect of a single
      amino acid substitution.
AB  - The 23-residue synthetic peptide representing the N-terminus of HIV-1 gp41 is
      known to induce either leakage or fusion of lipid vesicles depending on the
      experimental conditions. In this paper we report that a polar amino acid
      substitution V-->E at position 2, known to block gp41 activity in vivo, makes the
      peptide unable to destabilize and/or fuse membranes. Moreover this variant,
      unlike the parent peptide, is never found in the membrane-associated beta
      conformation.

PMID- 7720881
TI  - The arrestin superfamily: cone arrestins are a fourth family.
AB  - Arrestins constitute a superfamily of regulatory proteins that down-regulate
      phosphorylated G-protein membrane receptors, including rod and cone
      photoreceptors and adrenergic receptors. The potential role of arrestin in color
      visual processes led us to identify a cDNA encoding a cone-like arrestin in
      Xenopus laevis, the principle amphibian biological model system. Alignment of 18
      deduced amino acid sequences of all known arrestins from both invertebrate and
      vertebrate species reveals five arrestin families. Further analysis identifies 7
      variable and 4 conservative arrestin structural motifs that may identify
      potential functional domains. The adaptive evolutionary relationship of Xenopus
      cone arrestin to the arrestin gene tree suggests high intrafamily homology and
      early gene duplication events.

PMID- 7720882
TI  - Multimodality treatment of extra-visceral soft tissue sarcomas M0: state of the
      art and trends.
AB  - We here outline principles and trends in the treatment of soft tissue sarcomas
      without distant metastases (M0). Over the last 15 years significant advances have
      been made in the diagnostic imaging and histological classification of these
      tumors as well as in their treatment. Magnetic resonance imaging (MRI) has
      essentially replaced computerized tomography (CT) for the evaluation of the local
      growth pattern, although the latter is still preferred for the detection of
      pulmonary metastases. Immunohistochemistry techniques and electron microscopy
      have improved the histological diagnosis, although the results obtained should
      always be interpreted in the context of routine light microscopy. Adequate
      surgical resection and radiotherapy can reduce the incidence of local recurrence,
      which is still high for head-neck and retroperitoneal sarcomas. Limb-sparing
      surgery in combination with irradiation and/or intra-arterial or perfusion
      chemotherapy is considered the treatment of choice in 90% of limb sarcomas, with
      a local recurrence rate of less than 20%. New radiotherapeutical techniques and
      anti-neoplastic agents are now under investigation in an attempt to improve local
      control. There is also a need for a more effective adjuvant chemotherapy.
      Randomized clinical trials using doxorubicin/ifosfamide and growth factors are
      now underway.

PMID- 7720883
TI  - The ethics of randomized controlled trials.

PMID- 7720884
TI  - Making randomised trials larger: a simple solution?

PMID- 7720885
TI  - The value of guidelines in a breast screening service.
AB  - The use of agreed guidelines in the management of common surgical and medical
      conditions has received much attention and enjoys varying degrees of support. In
      May 1992 the UK Breast Screening Programme produced guidelines with the intention
      of providing criteria for all units to attempt to achieve. We have investigated
      these guidelines as a means of comparative audit and stimulus for change. Two
      units were compared, one in a teaching centre and the other in a district general
      hospital. Although both units performed for the most part within the guidelines,
      areas where improvement could be made were identified and measures to correct
      deficiencies taken. This resulted in improved performance in those areas. The
      study demonstrates that guidelines can have considerable benefit in helping to
      identify problems in the provision of care and introducing measures to improve
      the situation.

PMID- 7720886
TI  - A comparison of two surgical techniques for performing mastectomy.
AB  - Most surgeons performing mastectomy (MRM) use either the scalpel or
      electrocautery for developing flaps and performing node dissection. We report a
      retrospective analysis of all MRM performed over a five-year period by two
      surgical oncologists. One-hundred-and-ninety-six cases met criteria for inclusion
      into the study. There are 110 patients in the electrocautery (EC) group and 86
      patients in the scalpel (Scpl) group. Mean patient age, mean specimen weight and
      mean number of lymph nodes removed were not significantly different for the two
      groups. The incidence of complications was similar for the two groups. Mean
      estimated blood loss was 134.1 cc for the EC group and 331.6 cc for the Scpl
      group (P < 0.001). Estimated blood loss ranged from 25 to 475 cc for EC group and
      from 88 to 1350 cc for the Scpl group. One patient in the Scpl group required
      transfusion. Mean operating time was less for the Scpl group, 111.0 vs 93.5
      minutes (P < 0.009). Multiple regression analysis revealed that technique was the
      strongest predictor of estimated blood loss (standardized coefficient 0.61).
      Operating time, age, number of nodes removed and specimen weight were less
      predictive (standardized coefficient 0.21, 0.17, 0.11 and 0.09, respectively).

PMID- 7720887
TI  - The prognosis of stage III breast cancer treated with postoperative radiotherapy
      and adriamycin-based chemotherapy with and without tamoxifen. Eight year follow
      up results of a randomized trial.
AB  - Sixty-one patients with primary node positive stage III breast cancers were
      randomized to receive postoperative radiotherapy and doxorubicin-based
      chemotherapy (eight cycles of CAFt: cyclophosphamide, adriamycin, oral ftorafur)
      with or without tamoxifen as adjuvant treatment. The five-year overall survival
      for all patients was 49% (with tamoxifen 48% and without tamoxifen 50%) and
      disease-free survival 33% (with tamoxifen 27% and without 39%). Local control for
      all patients was only 64% despite the postoperative radiotherapy. There was no
      significant difference between these two treatment groups in overall and disease
      free survival or local control. The prognosis of stage III breast cancer remains
      grim despite modern adjuvant therapy. In addition to more effective systemic
      treatment more effective local therapy is also needed in order to obtain
      satisfactory local control. The most important studies in stage III breast cancer
      with 5-year survival results are reviewed here.

PMID- 7720888
TI  - Correlation of pS2 expression of involved lymph nodes in relation to primary
      breast carcinoma.
AB  - Expression of the pS2 protein in breast carcinoma is a useful guide to prognosis
      and response to tamoxifen. We have investigated pS2 protein expression in both
      the primary tumour and lymph node metastases (LNM) using a computer-assisted
      image analysis system. In a consecutive series of 208 patients undergoing
      surgical excision of primary breast cancer with axillary clearance, 89 patients
      were found to have involved lymph nodes. We found a highly significant
      correlation between pS2 expression in primary tumours and their LNM when 5% was
      taken as the cut-off for positive staining (Fischer Exact, P < 0.0001). There was
      also a highly significant correlation between the proportion of positive staining
      between the local metastases and primary tumours (Spearman's rank order
      correlation = 0.87; P < 0.0001). We conclude that the pS2 status of LNM can be
      accurately predicted from the pS2 status of the primary tumour. As such,
      appropriate adjuvant therapy for primary breast cancer, or second line therapy
      for disseminated disease can be selected on the pS2 status of the primary tumour
      alone.

PMID- 7720889
TI  - Lymphedema-induced lymphangiosarcoma.
AB  - A series of eight patients with chronic lymphedema-related lymphangiosarcoma is
      presented. All but one case showed a typical rapid progression and fatal outcome,
      as has been reported in other series. In one patient the lymphangiosarcoma
      developed on the chest wall, the axilla and the arm where persisting lymphedema
      and fibrosis occurred after bilateral mastectomy and bilateral postoperative
      radiotherapy. In this patient an asymptomatic course and slow locoregional
      progression of lesions was seen. The clinical picture, the etiological
      considerations and the therapeutic options of the lymphedema-induced
      lymphangiosarcoma with regard to the literature are discussed.

PMID- 7720890
TI  - Stomach cancer--is it a lost cause?
AB  - A retrospective study of 7 years of endoscopy at Trafford General Hospital from
      1986-1993 identified 143 patients diagnosed as having gastric cancer, of whom 13
      cases were identified as early gastric cancer. Epigastric pain was the main
      symptom (66%) of those presenting with resectable disease. Weight loss (70%) was
      the most common symptom of patients presenting with advanced disease. Forty-seven
      patients had no surgery and 25 had palliative non-resective surgery. These two
      groups account for 50% of cases. With such a small detection rate of early
      gastric cancer and consequent curative surgery rate one must debate whether
      treatment of stomach cancer in the Trust hospital of the future is a lost cause.

PMID- 7720891
TI  - Local recurrence and long-term survival in patients with gastric cancer--analysis
      of possible impact of clinicopathological parameters.
AB  - In a retrospective study comprising 88 patients operated upon with curative
      intent a number of histopathological parameters of possible prognostic value
      regarding local recurrence and long-time survival were analysed. Local recurrence
      within 5 years was found in 28 patients (32%) of which 17 (61%) were diagnosed
      within the first 2 years. Crude survival rates at 5 and 10 years were 25% and
      15%. According to Lauren's classification the results indicated better, but not
      significant, 5- and 10-year survival for the diffuse type (36% vs 25%). The
      probability of 10-year survival suggested a better (P = 0.06) prognosis for
      tumours in the middle third of the stomach, and for patients operated with total
      gastrectomy (P = 0.025). The probability of recurrence in relation to lymph node
      involvement suggested a more favourable prognosis (P = 0.06) for patients without
      lymph node metastases, and in relation to tumour fibrosis a less favourable
      prognosis for pronounced fibrosis (P = 0.001).

PMID- 7720892
TI  - Immunohistochemical expression of sialyl Tn and sialyl Lewis(a) antigens in
      stromal tissue correlates with peritoneal dissemination in stage IV human gastric
      cancer.
AB  - Immunohistochemical expression of sialyl Tn antigen (TKH2 and B72.3), sialyl
      Lewis(a) antigen (CA19-9) and CEA was examined in 52 cases with Stage IV gastric
      cancer, the objective being to examine whether or not these tumour-associated
      antigens show different expression between peritoneal dissemination and liver
      metastasis. Stromal type for TKH2, B72.3, CA19-9 and CEA were seen in 14 (50%),
      13 (46%), 18 (64%) and nine (32%) cases with peritoneal dissemination,
      respectively, and in four (17%), three (13%), four (17%) and four (17%) cases
      with liver metastasis, respectively. The stromal type correlated to peritoneal
      dissemination in TKH2 (P < 0.05) B72.3 (P < 0.05) and CA19-9 (P < 0.05). In other
      clinicopathological factors, the stromal type for TKH2, B72.3 and CA19-9
      correlated to the undifferentiated type. However, even in the undifferentiated
      type group, the stromal type correlated to peritoneal dissemination in TKH2 (P <
      0.05), B72.3 (P < 0.05) and CA19-9 (P < 0.05). Based on these results, the spread
      of sialyl-rich tumour-associated antigens into the surrounding stroma in the
      undifferentiated type of gastric cancer may be associated with peritoneal
      dissemination.

PMID- 7720893
TI  - A comparison of different techniques for liver resection: blunt dissection,
      ultrasonic aspirator and jet-cutter.
AB  - In a prospective study 116 patients underwent liver resection. Three different
      resection techniques, blunt dissection (n = 61), ultrasonic aspirator (CUSA) (n =
      27) and jet-cutter (n = 28) were compared. Speed of resection, blood loss,
      transfusion rate, liver hilus clamping time and tissue damage were evaluated on
      the basis of area of transected liver surface. Liver resection with the jet
      cutter was significantly faster with a resection time of 0.33 min/cm2 in
      comparison to blunt dissection (0.57 min/cm2) and CUSA (0.50 min/cm2) (P < 0.01)
      and associated with lower blood loss of 17.7 ml/cm2 (P < 0.01) than the other
      techniques (blunt dissection 32.5 ml/cm2, CUSA 24.3 ml/cm2). Tissue damage with
      respect to transaminases SGOT and SGPT was comparable to the other techniques.
      The jet-cutter is a promising new instrument in liver surgery.

PMID- 7720894
TI  - Preliminary report of tumor metastasis during liver regeneration after hepatic
      resection in rats.
AB  - In an attempt to ascertain possible facilitation of tumor metastasis during liver
      regeneration after hepatectomy, a series of experiments in rats was carried out
      using the RBT-1 carcinoma. WKA rats were separated into three groups: Group A
      received a sham operation; Group B underwent one-third hepatectomy; and Group C
      underwent two-thirds hepatectomy. Three groups had viable tumor cells injected
      into the tail vein after treatment. Survival period and lung metastases were
      analysed 14 days after initial injection of tumor. When comparisons were made
      between all groups, survival was shown to be significantly shorter in Group C
      than Group A (P < 0.05). The number of metastatic nodules in the lungs was
      significantly increased in Group B (P < 0.05) and C (P < 0.01), compared to Group
      A and in Group C, compared with Group B (P < 0.05). These results suggest that
      facilitation of tumor metastasis during liver regeneration may be proportional to
      the extent of liver resection.

PMID- 7720895
TI  - Intraoperative radiotherapy for primary and recurrent rectal cancer.
AB  - A total of 40 primary and 20 recurrent adenocarcinomas of the rectum were
      treated. Intraoperative radiation therapy was combined with pre- or postoperative
      irradiation and 5-FU and leucovorin treatment. An abdomino-perineal excision was
      performed in 32 and an anterior resection in 26 cases. A Hartmann's procedure was
      performed in two patients. Forty-two tumours were completely resected. Residual
      disease was microscopically detectable in 10 cases. In eight patients, tumour
      residual was evident macroscopically. Postoperatively, wound infection was
      observed in six and anastomotic dehiscence in four cases. After a follow-up of 20
      months, 46 patients revealed no evidence of disease. Local recurrences and
      distant metastases were detected in two patients each. Ten patients died of their
      disease.

PMID- 7720896
TI  - Microsurgical neck dissection for metastasizing medullary thyroid carcinoma.
AB  - Surgery is the only accepted method for a potentially curative treatment of
      metastatic medullary cancer of the thyroid (MCT). Between 5/1988 and 2/94 53
      patients (mean age 43, 14-65 years) were treated. A total of 24 patients
      underwent surgery of both sides of the neck whereas 29 patients required only one
      side. Six months after surgery, a profound reduction in basal serum calcitonin
      levels (CT) was detected in all patients. Upon pentagastrin stimulation, CT
      levels remained suppressed in eight patients. A pathological increase of
      normalized basal CT values was noted in 33 patients. In 12 patients, basal CT
      concentrations remained elevated after surgery. We conclude that metastatic MCT
      can be effectively treated by microsurgical modified radical neck dissection.

PMID- 7720897
TI  - Supratentorial low grade gliomas in adults. A retrospective analysis of 43 cases
      treated with surgery and radiotherapy.
AB  - Forty-three adults with histologically verified low grade gliomas, treated with
      post-operative radiotherapy between 1983 and 1991, were reviewed. Previous
      studies have identified age and extent of surgery as prognostic factors for
      survival. In this series, there was no significant difference between patients
      under 40 years of age and those 40 and over, nor was there a survival difference
      between those who had open biopsy and those who underwent subtotal/total
      resection. Patients with seizures preoperatively showed improvement in epileptic
      control at one year post-radiation. Clinical performance status and neurological
      deficit scoring indicated good preservation of function one year after radiation.

PMID- 7720898
TI  - Total vermilionectomy; indications and technique.
AB  - In this study, total vermilionectomy, indications and technique are discussed.
      The results of 33 cases are presented with review of the literature.

PMID- 7720899
TI  - Oesophageal varices: a potentially fatal complication of liver metastases.
AB  - Haemorrhage from oesophageal varices is a common and potentially life-threatening
      complication of portal hypertension, which is usually due to cirrhosis of the
      liver. Although liver metastases and hepatic dysfunction frequently occur in
      malignant disease, reports of oesophageal varices arising as a consequence of
      metastatic liver disease are sporadic, suggesting that this complication is
      unusual. Indeed, one review of the literature identified only 23 cases, although
      a few others have subsequently been reported. The management of such patients
      bleeding from oesophageal varices is clearly very different from bleeding due to
      other causes such as peptic ulceration. We report three cases and review the
      literature. All of our cases presented to us within a period of one year,
      suggesting that this complication of metastatic liver disease is more common than
      originally considered to be the case.

PMID- 7720900
TI  - Malignant neuroepithelioma of the colon.
AB  - A rare case of malignant peripheral neuroepithelioma originating from the right
      colon is presented. The patient underwent right hemicolectomy followed by
      combination chemotherapy and there has been no evidence of tumour recurrence or
      metastases during three years of follow up. Emphasis is given to the extremely
      unusual location of this tumour and the favorable clinical outcome.

PMID- 7720901
TI  - Diabetic fibrous breast disease: a clinical entity that mimics cancer.
AB  - Three typical cases of fibrous mastopathy associated with diabetes mellitus are
      described. The histological change is a connective-tissue overgrowth with
      vasculitis and some proliferation of duct epithelium. The clinical changes are
      indistinguishable by physical or radiographic findings from malignancy. In young
      patients with long-standing diabetes the presence of one or more suspicious
      clinical and imaging findings can suggest the presence of this lesion but a
      surgical biopsy or, at least, a close follow-up is required.

PMID- 7720902
TI  - Malignant fibrous histiocytoma of the breast.
AB  - Primary malignant fibrous histiocytoma of the female breast (MFH) occurs very
      rarely, and only 22 cases have been reported so far. We describe a 42-year-old
      female in whom MFH of the breast was diagnosed, and review the available
      literature. In accordance with knowledge concerning the biological and clinical
      behaviour of breast MFH, either wide local excision or mastectomy combined with
      axillary lymph nodes dissection is recommended, due to the high rate of
      recurrence and metastatic potential of this tumour.

PMID- 7720903
TI  - Lymphangiosarcoma. Reports of 3 cases and review of the literature.
AB  - Three cases of lymphangiosarcoma have been followed recently. All were finally
      treated by amputation. Only one is actually disease-free. The other two developed
      local recurrence at the thoracic cage. An extensive review of the literature
      follows the case presentation.

PMID- 7720904
TI  - Neurogenic tumors of the mediastinum originated from the vagus nerve.
AB  - Thirty-nine patients with neurogenic tumors observed between 1974 to 1992 were
      reviewed. There were 32 patients with neurilemoma, one with neurofibroma, five
      with ganglioneuroma, and one with malignant neurilemoma. Two cases of neurilemoma
      originated from the vagus nerve, which is very rare. Surgical resection is
      recommended, not only to confirm the nature of the lesion, but also to prevent
      further growth and compression on adjacent structures. For benign encapsulated
      neurogenic tumors, resection is curative.

PMID- 7720905
TI  - Paediatric surgical oncology. 3--Bone tumours.
AB  - Bone tumours are rare--they represent less than 1% of all malignancies but about
      6% in the paediatric population. Early diagnosis, chemotherapy and limb salvage
      surgery can result in 60% cure rates with a near normal functional outcome.
      Surgery plays a major part in the management of these tumours, and is
      technologically as well as surgically exacting.

PMID- 7720906
TI  - Synthetic polyribonucleotides: current role and potential use in oncological
      practice.
AB  - Polyadenylic-polyuridylic acid (PAPU) has a wide range of effects on various
      immunological cells and functions. It has been shown to enhance cellular and
      humoral immunity, in particular anti-cancer host defences, in both animals and
      man. In a small number of clinical trials (breast and stomach cancers) it appears
      to have a beneficial adjuvant effect, in terms of prolongation of disease-free
      and overall survival. Side effects with PAPU are minimal. The precise mode of
      action of PAPU is unclear and the most beneficial therapeutic regimen has yet to
      be established. PAPU, therefore, merits further careful consideration and
      evaluation. This article reviews its present status and considers further
      priority areas for investigation.

PMID- 7720907
TI  - Serum total renin is elevated in women with polycystic ovarian syndrome.
AB  - OBJECTIVE: To examine the serum total renin in women with polycystic ovarian
      syndrome (PCOS) and in controls. SETTING: Outpatient clinic of reproductive
      endocrinology at Turku University Central Hospital, Turku, Finland. PATIENTS:
      Forty-four oligomenorrheic women with PCOS (body mass index [BMI] 18.0 to 49.0
      kg/m2) and 25 control women with regular menstrual cycles (BMI 18.0 to 53.5
      kg/m2). MAIN OUTCOME MEASURES: The concentrations of total renin, LH, FSH, T,
      androstenedione (A), sex hormone-binding globulin (SHBG), and insulin in serum.
      RESULTS: The concentration of total renin in serum was higher in PCOS women than
      in healthy women independently of BMI, age, or serum insulin. The serum total
      renin measurement discriminated PCOS patients and control women to a similar
      extent as the previously used hormonal parameters (LH:FSH, T, A, and T:SHBG) as
      judged by receiver-operating characteristic analysis. Positive correlations were
      found between the serum total renin level and LH concentration, LH:FSH ratio, T
      and A levels, and T:SHBG ratio. Analysis of serum total renin in PCOS patients
      during oligomenorrhea and after menstruation did not reveal any significant
      changes. CONCLUSIONS: The elevated concentration of serum total renin suggests an
      enhanced activity of ovarian renin-angiotensin system in PCOS. The determination
      of serum total renin may provide a novel tool in the diagnostics of PCOS, because
      its serum level is elevated in PCOS women independently of BMI and serum insulin.

PMID- 7720908
TI  - Endocervical mucus pH is inversely related to serum androgen levels and waist to
      hip ratio.
AB  - OBJECTIVE: To determine whether an inter-relationship exists between endocervical
      mucus pH, serum androgen levels, and waist to hip (W:H) ratio. SETTING: Donor
      insemination clinic, University of Sheffield, Jessop Hospital, Sheffield, United
      Kingdom. PATIENTS: One hundred patients receiving donor insemination.
      INTERVENTIONS: Waist, hip, height, and weight measurements were recorded for 100
      patients receiving donor insemination. At the onset of the LH surge when patients
      attended for their first insemination, a sample of endocervical mucus and blood
      was taken. The Insler score of the mucus was recorded and the pH was measured
      with multirange pH paper. Of the 100 patients studied, 10 cases had an
      endocervical mucus pH < 6 despite Insler scores of > 10. Serum T, DHEAS, and
      androstenedione levels were measured in the 10 patients with pH < 6 and in 26
      patients selected at random from the 90 patients with pH > or = 6. RESULTS: The
      W:H ratio was significantly higher in the patients with pH < 6 than pH > or = 6.
      No significant difference was seen in body mass index between the latter groups.
      All serum androgen levels were significantly higher in the patients with pH < 6
      than pH > or = 7. CONCLUSION: A potential link (serum androgen levels) between a
      powerful predictive factor of fertility (W:H ratio) and a potential mechanism of
      subfertility (low endocervical mucus pH) has been demonstrated. This observation
      warrants further detailed evaluation particularly as it has been shown that a low
      endocervical mucus pH may be corrected by simple inexpensive treatment.

PMID- 7720909
TI  - Hysteroscopic cannulation for proximal tubal obstruction: a change for the
      better?
AB  - OBJECTIVE: To compare overall the results of hysteroscopic tubal cannulations and
      resection anastomosis for proximal tubal occlusion. DESIGN: Nonrandomized
      retrospective analysis of patients operated on by two surgeons. SETTING:
      University and large tertiary referral private practice. PATIENTS: Seventy-four
      patients over a 10-year period, with bilateral or unilateral proximal occlusion
      of a single tube. INTERVENTIONS: Hysteroscopic cannulation, resection
      anastomosis, or both. MAIN OUTCOME MEASURES: Intrauterine and ectopic pregnancy
      rates, long-term tubal patency, and pathology of tubal segments. RESULTS: In
      patients with normal distal tubes, intrauterine pregnancy rates were similar
      (12/21, 57% versus 12/24, 50%) and ectopic pregnancy rates were lower (0/21, 0%
      versus 7/24, 29.1%) in the cannulation group. One-year patency rates in
      nonpregnant patients was higher in the anastomosis group (12/15, 80% versus 3/8,
      33%). CONCLUSIONS: Hysteroscopic cannulation should be first choice in the
      management of proximal tubal obstructions in selected patients. It may be a
      treatment option for delayed occlusion after successful cannulation or resection
      anastomosis.

PMID- 7720910
TI  - Accuracy of hysterosalpingography and laparoscopic hydrotubation in diagnosis of
      tubal patency.
AB  - OBJECTIVE: To compare the diagnostic accuracy of two methods of assessment of
      tubal patency, viz, hysterosalpingography (HSG) and laparoscopic hydrotubation.
      DESIGN: One hundred four infertile women who were investigated with both HSG and
      laparoscopy in King Khalid University Hospital were selected for the study.
      Complete history of factors that may predispose to tubal occlusion was obtained.
      Patients with problems of ovulatory failure or poor semen analysis that may
      contribute to their infertility were excluded. RESULTS: The overall agreement
      between the two methods was 62.5%. However, the diagnostic accuracy of the two
      methods differed significantly. CONCLUSION: It would appear that laparoscopic
      hydrotubation, despite its invasive nature, had an edge in diagnostic accuracy
      when compared with HSG. It would be advantageous to subject patients in whom HSG
      has shown tubal blockage to laparoscopy or any of the newer techniques of
      hysteroscopy or sonographic hydrotubation.

PMID- 7720911
TI  - Expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane) is superior to
      oxidized regenerated cellulose (Interceed TC7+) in preventing adhesions.
AB  - OBJECTIVE: To compare the impact of expanded polytetrafluoroethylene (PTFE; Gore
      Tex Surgical Membrane; W. L. Gore & Associates, Inc., Flagstaff, AZ) and oxidized
      regenerated cellulose (Interceed TC7, Johnson & Johnson Medical, Inc., Arlington,
      TX) on the development of postsurgical adhesions. DESIGN: A multicenter,
      nonblinded, randomized clinical trial. SETTING: University medical centers.
      INTERVENTIONS: Each barrier was allocated randomly to the left or right sidewall
      of every patient. PATIENTS: Thirty-two women with bilateral pelvic sidewall
      adhesions undergoing reconstructive surgery and second-look laparoscopy. MAIN
      OUTCOME MEASURES: Adhesion score (on a 0- to 11-point scale), the area of
      adhesion (cm2), and the likelihood of no adhesions. RESULTS: The use of both
      barriers was associated with a lower adhesion score and area of adhesion
      postoperatively. However, those sidewalls covered with PTFE had a significantly
      lower adhesion score (0.97 +/- 0.30 versus 4.76 +/- 0.61 points, mean +/- SEM)
      and area of adhesion (0.95 +/- 0.35 versus 3.25 +/- 0.62 cm2). Overall, more
      sidewalls covered with PTFE had no adhesions (21 versus 7) and, when adhesions
      were present on the contralateral sidewall, the number of sidewalls covered with
      PTFE without adhesions was greater than those covered with oxidized regenerated
      cellulose (16 versus 2). CONCLUSION: Expanded polytetrafluoroethylene was
      associated with fewer postsurgical adhesions to the pelvic sidewall than oxidized
      regenerated cellulose.

PMID- 7720912
TI  - Replacement of dehydroepiandrosterone enhances T-lymphocyte insulin binding in
      postmenopausal women.
AB  - OBJECTIVE: To demonstrate bioavailability of 3 weeks of oral micronized DHEA and
      to delineate changes induced on insulin sensitivity, morphometric indexes, and
      lipoprotein profiles. DESIGN: Oral micronized DHEa (50 mg/d) was administered in
      3-week treatments to 11 postmenopausal women in a prospective, placebo
      controlled, randomized, blinded, crossover trial with an interarm washout. After
      dose (23 hour) serum DHEA, DHEAS, T, and cortisol levels were measured, as were
      fasting lipoproteins, oral glucose tolerance tests (OGTT), T-lymphocyte insulin
      binding and degradation, and urine collagen cross-links. Morphometric changes
      were determined by hydrostatic weighing. RESULTS: Dehydroepiandrosterone sulfate,
      DHEA, T, and free T increased up to two times premenopausal levels with
      treatment. Fasting triglycerides declined; no change in collagen cross-links or
      morphometric indexes was noted. Oral glucose tolerance test parameters did not
      change, but both T-lymphocyte insulin binding and degradation increased with
      DHEA. CONCLUSION: Fifty milligrams per day of oral DHEA gives suprahysiologic
      androgen levels; 25 mg/d may be more appropriate. Dehydroepiandrosterone enhanced
      tissue insulin sensitivity and lowered serum triglycerides. Rationale is provided
      for postmenopausal replacement therapy with this androgen.

PMID- 7720913
TI  - In vitro fertilization outcome in the presence of severe male factor infertility.
AB  - OBJECTIVE: To assess the outcome of standard IVF treatment (nonmicromanipulated)
      with respect to total motile sperm number recovered by swim-up, particularly for
      couples with severe male factor infertility defined as total motile sperm number
      < 0.5 x 10(6). DESIGN: Retrospective study of patients who underwent successful
      oocyte retrieval in an IVF program from August 10, 1992 to December 31, 1993.
      SETTING: A university-based tertiary referral center (The Toronto Hospital).
      PATIENTS: All cycles (n = 672) were divided into four groups according to total
      motile sperm number recovered using standard swim-up: group 1, total motile sperm
      number < or = 0.50 x 10(6); group 2, total motile sperm number between 0.51 and
      1.00 x 10(6); group 3, total motile sperm number between 1.01 and 1.50 x 10(6);
      and group 4, total motile sperm number > or = 1.51 x 10(6). All patients received
      the same controlled ovarian hyperstimulation protocol, which consisted of a GnRH
      analog flare-up followed by parenteral menotropins. Clinical and cycle
      characteristics in the four groups were analyzed and outcome was evaluated.
      RESULTS: There was no significant difference in clinical and cycle
      characteristics between the groups. The uniformity of the groups justified
      analysis of their outcome. A fertilization rate of 21.5% was achieved in couples
      with severe male factor (group 1). Fertilization rate and number of embryos
      transferred increased directly with the total motile sperm number. There was no
      significant difference in implantation rate per embryo between the groups.
      CONCLUSIONS: The results in couples with severe male factor infertility compare
      favorably with monospermic fertilization rates reported in the literature using
      partial zona dissection and subzonal insertion but is lower than with
      intracytoplasmic sperm injection. Therefore, we believe that couples with severe
      male factor infertility should be considered for standard IVF, as long as
      adequate total motile sperm can be recovered (100 x 10(3) per dish). If
      intracytoplasmic sperm injection is available, it should be offered to these
      couples.

PMID- 7720914
TI  - Percutaneous epididymal sperm aspiration and intracytoplasmic sperm injection in
      the management of infertility due to obstructive azoospermia.
AB  - OBJECTIVE: To evaluate the recovery rate of spermatozoa from the epididymis using
      a percutaneous aspiration technique and to examine the fertilization rate after
      intracytoplasmic sperm injection. DESIGN: Prospective observational study.
      SETTING: Private infertility clinic, London. SUBJECTS: Twenty patients with
      obstructive azoospermia who each had an attempt at IVF. The sperm used for
      intracytoplasmic sperm injection was retrieved by percutaneous epididymal sperm
      aspiration in 16 patients. In one patient, microepididymal sperm aspiration was
      performed in addition because the quality of the sperm obtained by percutaneous
      epididymal sperm aspiration was not considered suitable for microinjection. In
      the remaining three patients, neither percutaneous epididymal sperm aspiration
      nor microepididymal sperm aspiration resulted in the recovery of sperm, which was
      obtained by testicular biopsy in one of them. INTERVENTION: Assisted
      fertilization with intracytoplasmic sperm injection. MAIN OUTCOME MEASURES:
      Normal fertilization and pregnancy rates. RESULTS: A total of 179 eggs were
      collected and 157 subsequently were microinjected. Normal fertilization occurred
      in 22 oocytes (14%) and the total number of embryos cleaved was 30. Twelve
      patients underwent ET in which three conceived (pregnancy rate 25% per transfer).
      The implantation rate was 10% and failed fertilization occurred in four cycles.
      CONCLUSION: Percutaneous epididymal sperm aspiration can be used successfully to
      recover sperm in men with obstructive azoospermia for use in assisted
      fertilization IVF cycles. The technique is simple, effective, and less traumatic
      compared with an open microsurgical operation.

PMID- 7720915
TI  - Transfer of six or more embryos improves success rates in patients with repeated
      in vitro fertilization failures.
AB  - OBJECTIVE: To examine the results of six or more embryos transferred to patients
      whose IVF-ET cycles repeatedly met with failure. DESIGN: Prospective clinical
      evaluation of pregnancy rates and pregnancy outcome. SETTING: IVF-ET Unit.
      PATIENTS: Seventy-two IVF patients who had failed at least four previous IVF
      cycles. INTERVENTIONS: Forty-one patients (group A) received six or more embryos,
      and 31 patients (group B) chose to receive five embryos. MAIN OUTCOME MEASURES:
      Per embryo implantation rate, pregnancy rate, multiple pregnancies, and outcome
      were evaluated. RESULTS: With the transfer of six or more embryos, the pregnancy
      rate was significantly higher than with the transfer of five embryos (56% versus
      29%, respectively). This was associated with a slight, but insignificant,
      increase in multiple gestations. No difference in pregnancy outcome was noted
      among the groups. CONCLUSIONS: Patients who have had repeated IVF failures may
      have higher pregnancy rates if six or more embryos are transferred in subsequent
      cycles.

PMID- 7720916
TI  - Psychological study of in vitro fertilization-embryo transfer participants'
      attitudes toward the destiny of their supernumerary embryos.
AB  - OBJECTIVE: To study the motivations underlying IVF-ET participants' choice to
      donate or destroy their supernumerary embryos. DESIGN: Couples' opinions are
      studied through a questionnaire and a psychological interview. PARTICIPANTS: Two
      hundred couples about to undergo IVF-ET. SETTING: The fertility unit of an
      academic hospital. MAIN OUTCOME MEASURES: Couples' choice for supernumerary
      embryos' destiny; opinions on embryo status, on importance of genetic lineage in
      the filial bonding, on gamete donation, and on multiple pregnancy risk. RESULTS:
      Donation is the most frequent choice but destruction is tolerated by almost all
      the couples (92%). Couples considering the embryo as a child choose destruction
      as frequently as donation but refuse experimentation on the embryo. Donation is
      highest among couples who stress education more than genetic lineage in parental
      bonding. This is confirmed by the choice of the couples requiring donor gametes.
      Couples express differing attitudes toward risks of twins and risks of triplets:
      twins are much more desired than triplets, which are frequently refused.
      CONCLUSIONS: Couples' opinions on the respective importance of genetic lineage
      and education in defining parental bonding are more determinant in their decision
      to destroy or to donate their supernumerary embryos than their opinions on the in
      vitro embryo status, which only determines their attitude toward experimentation.

PMID- 7720917
TI  - Application of multivariate cluster, discriminate function, and stepwise
      regression analyses to variable selection and predictive modeling of sperm
      cryosurvival.
AB  - OBJECTIVE: To develop a mathematical model that predicts sperm cryodamage based
      on the kinematic characteristics of seminal sperm as detected by computer-aided
      sperm analysis (CASA). DESIGN: Computer-aided sperm analysis was performed on
      donor semen before and after freezing. An iterative multivariate statistical
      analysis technique was developed to identify sperm subpopulations and to select
      the best variables for modeling. Stepwise, multivariate regression was performed
      on the selected subpopulations to predict the post-thaw percentage of motile
      sperm from prefreeze kinematic values. SETTING: Andrology laboratories, IVF
      laboratories, and sperm cryobanks. PARTICIPANTS: Semen donors in an academic
      research environment. MAIN OUTCOME MEASURES: Identification of predictive
      kinematic variables; number of sperm subpopulations per sample; number of
      kinematic variables per subpopulation; prediction error for subpopulation
      membership; and an equation for prediction of post-thaw percentage of motile
      sperm from prefreeze CASA variables. RESULTS: The number of subpopulations for
      each specimen was predicted by 3 to 5 kinematic variables. Straight-line velocity
      (VSL) and linearity were the most commonly predictive primary variables, whereas
      curvilinear velocity and amplitude of lateral head displacement were the most
      commonly predictive secondary variables. The best linear model predicted the post
      thaw percentage of motile sperm from the difference in VSL between the
      subpopulation with the highest value and the subpopulation with the lowest value
      in each prefreeze specimen. CONCLUSIONS: A small number of consistent kinematic
      variables accurately described physiologic subpopulations of sperm in prefreeze
      and post-thaw specimens from different men. An equation based on the
      characteristics of these subpopulations predicts the post-thaw percentage of
      motile sperm (i.e., sperm recovery) from simple prefreeze kinematic variables.
      This equation could improve specimen screening by eliminating the requirements
      for freezing and thawing in order to identify a specimen's vulnerability to
      cryodamage.

PMID- 7720918
TI  - A standardized test for visual analysis of human sperm morphology.
AB  - OBJECTIVES: To develop a method to train and test simultaneously a large number
      of observers in the practice of visual sperm morphology analysis. DESIGN:
      Photographs of fixed and stained sperm were prepared. Fields of suitable sperm
      images were selected and individual images were numbered on each negative. Two
      tests, which contained a total of 100 sperm images, were created. Thirty images
      in each test consisted of three repeats of 10 images, while 70 images in each
      test were unique. The tests were administered to individuals participating in an
      American Fertility Society postgraduate course. Sperm images were projected on a
      screen and participants classified each sperm using the method that was used in
      their own laboratory. SETTING: Postgraduate course of The American Fertility
      Society. RESULTS: The majority of individuals participating in the tests used
      some version of the World Health Organization method. The group using the Strict
      method reported a lower value for the percentage of normal sperm than the groups
      using the other methods. The variability for the percentage of normal sperm was
      highest for the Strict method. The degree of classification reversal, i.e.,
      classifying a sperm as normal during one repeat and then reversing the
      classification during another repeat, was high for all groups (26% to 44% of the
      classifications). Some degree of improvement was seen from test 1 to test 2.
      CONCLUSIONS: It is possible to develop efficient and inexpensive methods to train
      observers to perform the sperm morphology assay. Such methods also enable the
      objective measurement of the acquisition of proficiency, comparison between
      different classification methods, and identification of specific differences
      between observers. Such methods will become more important with implementation of
      the Clinical Laboratory Improvement Act.

PMID- 7720919
TI  - Analysis of TEST (TES and Tris) yolk buffer effects on human sperm.
AB  - OBJECTIVE: To assess different parameters of TEST (TES and Tris) yolk buffer
      (TYB) treatment of human sperm that may contribute to the biologic effects of TYB
      on sperm function. DESIGN: The influence of TYB treatment on occurrence of
      acrosome reactions was studied, as was the influence of the concentration of
      acrosome-reacted sperm reacted by TYB or Biggers-Whitten-Whittingham medium (BWW)
      incubation on penetration levels in the sperm penetration assay (SPA). The
      necessity for the TYB to achieve enhanced SPA performance as well as the effect
      of heat shock on sperm also were studied. SETTING: Andrology laboratory of a
      university hospital. PATIENTS: Sperm donors. MAIN OUTCOME MEASURES: Sperm
      penetration levels in the SPA and acrosomal loss as evaluated by a fluorescent
      lectin staining technique. RESULTS: Sperm incubated in TYB for 42 to 46 hours at
      4 degrees C demonstrated a higher rate of acrosomal loss than did sperm
      capacitated in BWW media for 20 to 22 hours. The difference was not significant.
      When insemination concentrations were normalized to identical concentrations of
      acrosome-reacted sperm, TYB treated specimens demonstrated much higher
      penetration levels compared with BWW specimens. Samples incubated in BWW versus
      TYB for 42 to 46 hours at 4 degrees C before heat shock had identical penetration
      levels. Samples washed with 37 degrees C BWW (positive heat shock) had
      significantly higher penetration levels than did samples washed with 4 degrees C
      BWW (negative heat shock). CONCLUSION: Although TYB treatment does increase the
      occurrence of acrosome reactions, this alone does not account for the dramatic
      increase in penetration levels in SPA seen with these samples. TEST yolk buffer
      is not required for enhancement of penetration, and the heat shock step of the
      procedure seems to be most important for enhancement of sperm fusion ability in
      the SPA.

PMID- 7720920
TI  - Assessment of the Sperm Quality Analyzer.
AB  - OBJECTIVE: To assess the relationship between the results of the Sperm Quality
      Analyzer (United Medical Systems Inc., Santa Ana, CA), which measures motile
      sperm concentration by light scattering, conventional manual semen analysis
      characteristics, and computer-assisted sperm motility analyses. DESIGN: Sperm
      Quality Analyzer measurements and manual and computer-assisted semen analyses
      were performed on 150 (50, 62, and 38) samples in three laboratories and the
      results were compared. SETTING: The study was performed in the Andrology
      Laboratory of Prince Henry's Institute of Medical Research, Monash Medical
      Centre, and Andrology Laboratory and Reproductive Biology Unit at the Royal
      Women's Hospital, Melbourne, Victoria, Australia. PATIENTS: Patients presented to
      the laboratories for routine fertility evaluation in the male and were selected
      at random to reflect the range of normal and abnormal samples seen in the
      laboratories. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Sperm count, motility
      (percent motility, motility index, velocity, and amplitude of lateral head
      displacement [ALH]), morphology, and normal acrosomes were evaluated by manual
      and computer-assisted semen analysis and sperm quality analyzer motility index.
      RESULTS: Spearman nonparametric univariate analysis showed strong correlations
      between sperm motility index and manual sperm concentration, motility, abnormal
      morphology, and normal acrosomes by Pisum sativum agglutinin; and computer
      assisted sperm motility analysis sperm concentration, motile concentration, and
      percent static. Curvilinear velocity, straight-line velocity (VSL), and linearity
      also were related significantly to sperm motility index values. By multiple
      regression analysis, the significant covariates of the sperm motility index were
      motile sperm concentration, abnormal morphology, ALH, and straight-line velocity
      and these accounted for 85.5% of the variance of the sperm motility index.
      CONCLUSIONS: The Sperm Quality Analyzer is easy to use. The good correlation
      between the sperm motility index, motile sperm concentration, and, in addition, a
      number of other semen parameters supports the use of the Sperm Quality Analyzer
      for screening patients and in situations that warrant a rapid verification of
      semen quality, such as in the IVF or artificial insemination clinic. Further
      investigation of the Sperm Quality Analyzer in the management of male infertility
      is warranted.

PMID- 7720921
TI  - Inability of human sperm to change their orientation in response to external
      chemical stimuli.
AB  - OBJECTIVE: To investigate whether human sperm can respond to external chemical
      stimuli by orienting themselves toward chemoattractants or withdrawing from
      hostile environments. DESIGN: Controlled laboratory assays. SETTING: Normal human
      sperm and two other flagellated micro-organisms were exposed to various potential
      chemoattractant or chemorepellent substances. INTERVENTION: Human sperm, Euglena
      viridis, and Escherichia coli were exposed to various substances from the female
      reproductive system or to various toxic agents by placing them within tiny wells
      in a sealed minichamber. They were followed by microscopic observation and by
      intermittent photography. MAIN OUTCOME MEASURE: Images of photographed micro
      organisms were analyzed for signs of attraction to or withdrawal from the test
      substances. RESULTS: Human sperm neither changed their orientation toward nor
      accumulated next to the well that contained cervical mucus, uterine cavity and
      follicular fluid, cumulus cells, or intact nonfertilized human eggs. Contrary to
      other micro-organisms that turned away from sources of hydrochloric acid, sodium
      hydroxide, ethanol, or glutaraldehyde, human sperm did not withdraw from these
      solutions. They swam along the ascending chemical gradient, facing ahead while
      becoming immobilized by these agents. CONCLUSION: It may be implied from the
      observation that they did not turn away from a hostile environment when expected
      to do so or turn toward chemoattractants that human sperm do not respond to
      external chemical stimuli and, most probably, chemotaxis between human sperm and
      ova in nature does not exist.

PMID- 7720922
TI  - Do spermatozoa secrete motility enhancing factor?
AB  - OBJECTIVES: To determine whether medium conditioned with human spermatozoa was
      capable of enhancing sperm motility and penetration ability. DESIGN: Paired
      aliquots of washed spermatozoa were allowed to incubate for nine different
      incubation periods, ranging from 15 to 240 minutes in 37 degrees C in humidified
      atmosphere with 5% CO2. After this, they were centrifuged at 600 x g for 6
      minutes. The conditioned medium was removed from one tube of each pair and
      replaced with fresh medium. In the other tube of the same pair the sperm pellet
      was resuspended in the same medium. In a second set of experiments, conditioned
      medium was removed from tubes containing samples of spermatozoa after different
      predefined incubation periods. This was used to replace medium that had been
      removed from sperm cells that had been incubated for 120 minutes. Motility and
      penetration of zona-free hamster eggs were assessed. RESULTS: Removal of the
      incubation medium at times between 15 to 240 minutes resulted in sperm that
      showed a gradual decrease in motility and penetration ability followed by a
      gradual increase in motility and penetration ability, i.e., an inverted bell
      shaped effect. The addition of conditioned medium obtained after different
      periods of incubation to spermatozoa where medium was removed after 120 minutes
      of incubation resulted in an increase in sperm motility and penetration ability.
      The longer the medium was conditioned with spermatozoa the more prominent the
      effect on sperm motility and penetration ability, with maximal effect observed
      with medium conditioned for 120 minutes. CONCLUSIONS: Medium conditioned with
      human spermatozoa enhances sperm motility and penetration ability.

PMID- 7720923
TI  - Treatment with 5-aminolevulinic acid and photoactivating light causes destruction
      of preimplantation mouse embryos.
AB  - OBJECTIVE: To evaluate the direct effect of photodynamic treatment with 5
      aminolevulinic acid (ALA) on preimplantation mouse embryos in an in vitro
      setting. DESIGN: Preimplantation mouse embryos were incubated with or without ALA
      for 5 hours and followed immediately by light exposure for 0, 5, or 15 minutes.
      Comparison of the viability and blastocyst formation was made among different
      treatment groups. SETTING: A conventional laboratory setting with embyro culture
      facilities. INTERVENTIONS: Female CD1 mice were superovulated with pregnant mare
      serum gonadotropin and hCG before mating. Four-and eight-cell embryos and
      compacted morulae were flushed from the oviducts and incubated with 0, 0.1, 0.5,
      1.0, or 5.0 mM ALA for 5 hours. Embryos subsequently were exposed to
      photoactivating light for 0, 5, or 15 minutes. MAIN OUTCOME MEASURES: Microscopic
      assessment of embryos quality at 12 hours and determination of the percentage of
      embryos progressing to the blastocyst stage at 36 or 60 hours. RESULTS:
      Incubation of embryos with 0.1, 0.5, 1.0, 5.0 mM ALA without light resulted in
      87.3% +/- 1.6%, 84.9% +/- 3.4%, 81.4% +/- 1.8%, and 82.8% +/- 4.7% of the embryos
      developing to blastocysts, respectively. In the absence of ALA, light exposure
      for 0, 5, or 15 minutes resulted in 93.8% +/- 2.3%, 92.3% +/- 2.2%, and 85.9% +/-
      1.7% blastocyst formation. Combining treatment of ALA at the same concentrations
      with light resulted in 33.3% +/- 2.1%, 0.7% +/- 0.9%, 0%, 0% (5-minute light),
      13.3% +/- 1.0%, 0%, 1.6% +/- 1.3%, 0% (15-minute light) blastocyst formation,
      respectively. When gross morphology was used to assess embryo viability at 12
      hours, similar results were observed. Measurement of the fluorescent spectrum of
      embryos incubated with ALA indicated that protoporphyrin IX had been formed.
      CONCLUSION: Photodynamic ablation of mouse embryos was achieved with ALA under in
      vitro conditions. These results indicate that preimplantation mouse embryos are
      capable of converting ALA to the photosensitizer, protoporphyrin IX, and are
      susceptible to subsequent photoablation. A photodynamic effect on the embryo may
      be important to the successful application of this technique to the treatment of
      human ectopic pregnancy.

PMID- 7720924
TI  - Gonadotropin-releasing hormone agonist therapy reduces postoperative adhesion
      formation and reformation after adhesiolysis in rat models for adhesion formation
      and endometriosis.
AB  - OBJECTIVES: To evaluate the effectiveness of GnRH agonist (GnRH-a) therapy on
      adhesion formation and reformation in established rat models for surgically
      induced adhesion formation and endometriosis. DESIGN: Before surgery, female
      Sprague-Dawley rats were injected with GnRH-a or control diluent. Six days later,
      rats were assigned to one of four surgical groups: [1] endometriosis, [2]
      endometriosis sham, [3] adhesion model, or [4] adhesion sham. Three weeks after
      surgery, a second-look laparotomy was performed, adhesions were scored (0 = no
      adhesions to 3 = severe adhesions) and mechanically disrupted, and rats received
      a second GnRH-a or diluent injection either analogous to their initial injection
      or in a crossover design. Three weeks after the second injection, rats were
      killed and adhesion reformation was scored. Data were evaluated using
      nonparameteric tests including Mann-Whitney, Kruskal-Wallis, and Friedman's tests
      comparing GnRH-a treatments with diluent controls. RESULTS: Preoperative GnRH-a
      therapy reduced adhesion scores in rats with surgically induced endometriosis
      (mean +/- SEM; GnRH-a 1.1 +/- 0.2 versus diluent 2.2 +/- 0.2) and adhesions (GnRH
      a 0.3 +/- 0.1 versus diluent 0.6 +/- 0.1). Pretreatment GnRH-a therapy did not
      affect adhesion scores in the endometriosis sham procedure. Combined preoperative
      and postoperative GnRHa therapy (GnRH-a-GnRH-a) but not postoperative GnRH-a
      therapy alone (diluent-GnRH-a) reduced adhesion reformation after adhesiolysis in
      the endometriosis model (GnRH-a-GnRH-a 1.1 +/- 0.3, diluent-GnRH-a 1.6 +/- 0.7),
      the endometriosis sham (GnRH-a-GnRH-a 0.7 +/- 0.2, diluent-GnRHa 1.8 +/- 0.1),
      and the adhesion model (GnRH-a-GnRH-a 0.3 +/- 0.2, diluent-GnRHa 1.0 +/- 0.5). No
      adhesions were observed in the adhesion sham group. CONCLUSIONS: Gonadotropin
      releasing hormone agonist therapy was successful in reducing adhesion formation
      and reformation. These studies suggest that GnRH-a therapy for adhesion
      prevention in women should be explored.

PMID- 7720925
TI  - The revised American Fertility Society classification of endometriosis:
      reproducibility of scoring. ZOLADEX Endometriosis Study Group.
AB  - OBJECTIVE: To assess the reproducibility in staging endometriosis using the
      revised American Fertility Society (AFS) classification of endometriosis. DESIGN:
      Visual documentation of laparoscopies of 315 women with endometriosis was scored
      by the investigators and a blinded reviewer. SETTING: Patients from private
      practice institutional setting. PARTICIPANTS: Patients who participated in a
      multicenter trial to study the efficacy and safety of a GnRH agonist (GnRH-a).
      INTERVENTIONS: Laparascopic visual documentation of the extent of endometriosis
      before and after 6 months of GnRH-a therapy. MAIN OUTCOME MEASURE: The
      reproducibility of the AFS classification system comparing scoring during
      laparoscopy and by a blinded reviewer. RESULTS: Good to fair agreement scoring
      endometriosis between the investigator and the blinded reviewer was noted.
      CONCLUSIONS: Visual documentation may be used to determine the stage of
      endometriosis using the revised AFS classification guidelines.

PMID- 7720926
TI  - Administration of a gonadotropin-releasing hormone agonist during pregnancy:
      follow-up of 28 pregnancies exposed to triptoreline.
AB  - OBJECTIVE: To evaluate the teratogenic or fetal risk of a long-acting GnRH
      agonist (GnRH-a) triptoreline acetate (Decapeptyl; Ipsen-Biotech, Inc., Paris,
      France), inadvertently administrated in the first weeks of pregnancy. DESIGN:
      Prospective follow-up of exposed pregnancies and case reports. SETTING:
      Teratology information service of a public hospital and pharmacovigilance
      department of the firm. PATIENTS: Inadvertent pregnant women receiving a
      treatment, mainly for endometriosis or IVF. INTERVENTIONS: Case by case,
      individual estimations of the risks have been provided. MAIN OUTCOME MEASURE:
      Each pregnancy issue has been analyzed. RESULTS: No teratogenic or fetal toxic
      effect has been noted. CONCLUSION: No specific hazard has been observed among
      newborns after inadvertent exposures to a GnRH-a during the first 20 weeks of
      pregnancy.

PMID- 7720927
TI  - Chest tube drainage of pleural effusion correcting abdominal ascites in a patient
      with severe ovarian hyperstimulation syndrome: a case report.
AB  - OBJECTIVE: To describe a patient with severe ovarian hyperstimulation syndrome
      (OHSS) demonstrating a beneficial result of reduction in abdominal ascites with a
      chest tube placed for bilateral pleural effusions. DESIGN: Case report. SETTING:
      Academic hospital. PATIENT: A 28-year-old white female with primary infertility
      on hMG (Pergonal; Serono Laboratories, Randolph, MA) therapy. INTERVENTIONS:
      Intravenous fluids, lasix, and albumin were administered for correction of
      laboratory abnormalities, including hemoconcentration, hypoalbuminemia, and
      leukocytosis. A chest tube was placed for treatment of pleural effusions. MAIN
      OUTCOME MEASURES: Laboratory values of hematologic measures and electrolytes.
      Resolution of pleural effusions and abdominal ascites as determined by chest
      roentgenogram and physical examination. RESULTS: Treatment of OHSS with
      intravenous fluids, lasix, and albumin corrected the hemoconcentration,
      hypoalbuminemia, and leukocytosis associated with OHSS. Placement of a chest tube
      corrected the pleural effusions and abdominal ascites. CONCLUSION: This case
      report demonstrates a beneficial result of reduction in abdominal ascites by a
      chest tube placed for pleural effusions.

PMID- 7720928
TI  - Intracytoplasmic sperm injection, fertilization, and embryo transfer after
      retrieval of spermatozoa by testicular biopsy from an azoospermic male with
      testicular tubular atrophy.
AB  - OBJECTIVE: To achieve fertilization and cleavage by spermatozoa retrieved by
      testicular biopsy from a male with testicular tubular atrophy. DESIGN: Clinical
      trial. SETTING: Private reproductive institute. PATIENT: Azoospermic male with
      demonstrated testicular tubular atrophy and almost complete spermatogenic arrest.
      INTERVENTION: Open biopsy retrieval of testicular tissue and sperm followed by
      intracytoplasmic sperm injection. MAIN OUTCOME MEASURES: Fertilization and
      cleavage. RESULTS: One four- to six-cell embryo was formed after intracytoplasmic
      sperm injection of five eggs with extruded polar bodies by retrieved sperm.
      CONCLUSION: Intracytoplasmic sperm injection after testicular sperm aspiration
      may be attempted in cases with severely decreased spermatogenesis and result in
      fertilization, cleavage, and embryo transfer.

PMID- 7720929
TI  - Sperm as a noninvasive gene delivery system for preimplantation embryos.
AB  - OBJECTIVE: To determine if sperm could be manipulated to be a noninvasive
      transport carrier for the delivery of gene fragments to the blastocyst. DESIGN:
      Sperm cells carrying foreign DNA fragments from human papillomavirus (HPV) types
      16, 18, 31, and 33 were allowed to migrate from one end of an artificial
      reproductive tube and to come in contact with hatching mouse blastocysts at the
      other end of the tube. The blastocysts were then washed and analyzed for the
      presence of the foreign DNA fragments. SETTING: Clinical and academic research
      environment. MAIN OUTCOME MEASURE: Detection of amplified products from
      transferred foreign DNA using the polymerase chain reaction and primers targeted
      at the E6-E7 region for different HPV types. RESULTS: Polymerase chain reaction
      analyses showed transference of DNA HPV type 18 to the blastocysts. Not all types
      of DNA fragments were transferred equally. CONCLUSION: The results suggested the
      possibility of using sperm as a noninvasive gene delivery system for passing on
      gene fragments to preimplantation embryos. It was demonstrated that certain DNA
      fragments were easier to deliver than others, indicating the necessity for
      exploring all the factors involved in the mechanism of the transference process.
      The study also serves to highlight the possibility of unintentional transmission
      of viral or bacterial DNA to the developing embryo via the sperm.

PMID- 7720930
TI  - Evaluation of sperm morphology of electroejaculates of spinal cord-injured men by
      strict criteria.
AB  - OBJECTIVE: To compare sperm morphology of electrostimulated ejaculates of spinal
      cord-injured (SCI) men with that of manual ejaculates of an able-bodied
      population. DESIGN: Retrospective study. PATIENTS: Spinal cord-injured men (n =
      21) participating in a reproductive rehabilitation program and able-bodied men (n
      = 163) attending a male fertility clinic. SETTING: Male fertility clinic of a
      university urology practice. MAIN OUTCOME MEASURES: Morphological characteristics
      of sperm evaluated by strict criteria. RESULTS: Electroejaculates of SCI men had
      significantly higher percentages of small sperm heads, vacuolated sperm heads,
      and sperm with tail defects than found in manual ejaculates of able-bodied men.
      Cellular elements of nongerminal origin (white blood cells, red blood cells,
      epithelial cells) were also more likely to be present in electroejaculates.
      CONCLUSION: When evaluated by strict criteria, electroejaculates exhibit specific
      defects in sperm morphological profile. A pervasive pattern of teratozoospermia
      exists that may reflect underlying defects contributing to decreased fertility in
      SCI men.

PMID- 7720931
TI  - Improved accuracy of sperm motility assessment using a modified Micro-Cell sperm
      counting chamber.
AB  - OBJECTIVE: To assess the effect of modifications made in the Micro-Cell sperm
      counting chamber on the motility of washed human spermatozoa. DESIGN: In a 2 x 2
      experimental design, human sperm samples were washed with or without protein
      supplementation, loaded into modified or unmodified Micro-Cell chambers, and
      assessed by automated semen analysis for changes associated with sperm adhesion
      to the glass chamber surfaces. PARTICIPANTS: Twenty-one men who were undergoing
      semen analysis and presented with > or = 50% motile sperm, or normal donors. MAIN
      OUTCOME MEASURES: Reduced motility and elevated lateral head displacement
      associated with sperm adhesion to glass surfaces were compared using a doubly
      repeated measures analysis of variance. RESULTS: Addition of protein to the sperm
      washing solution partially reversed the adhesion of spermatozoa to the glass of
      unmodified Micro-Cell chambers. Chambers manufactured to reduce cell adhesion to
      glass surfaces yielded the highest motility and lowest lateral head displacement,
      whether the sperm were washed in a solution supplemented with or without protein.
      CONCLUSION: These findings indicate that, as in raw semen, kinematics of washed
      sperm can be measured reliably in the modified Micro-Cell chamber.

PMID- 7720932
TI  - Menstrual "asthma"--therapy?

PMID- 7720933
TI  - Recurrent abortion and leukocyte therapy--long-term benefits?

PMID- 7720934
TI  - Future of the hamster oocyte penetration assay?

PMID- 7720935
TI  - Contribution of estrogen to the morphology of "secretory" endometrium?

PMID- 7720936
TI  - Predictive value of color Doppler for ovarian endometrioma.

PMID- 7720937
TI  - Earthquakes and prions.

PMID- 7720938
TI  - Marketed sperm: use and regulation in the United States.
AB  - OBJECTIVE: To collate information relating to the current use of marketed semen
      for therapeutic donor insemination (DI) in the United States. DATA
      IDENTIFICATION: Literature was identified by Medline search and government
      document review. LITERATURE SELECTION: Materials selected for review included
      empirical studies, policy reviews, legal documents, and government surveys
      relating to use of donor sperm. RESULTS: Use of marketed (donor) sperm is
      associated with significant medical, genetic, and psychological risk. These risks
      directly affect the individuals involved in therapeutic DI. Also, the public's
      health is involved because these risks include transmission of infectious disease
      and genetic anomalies. Legal and social concerns associated with therapeutic DI
      include offspring's knowledge of genetic endowment, parental responsibility, and
      donor confidentiality. This analysis shows that policies currently in place
      regarding the use of marketed semen in therapeutic DI do not ensure consumer
      safety and do not protect society's interest. CONCLUSIONS: Current policies need
      to be improved to protect those directly involved in the therapeutic DI process
      and to address public health and societal concerns. Recommendations include: [1]
      programs to assure quality and safety of marketed sperm, [2] implementation of a
      central registry to collect information about the use and outcomes of therapeutic
      DI, and [3H] expansion of available therapeutic DI guidelines to address
      psychological and social support for persons involved in therapeutic DI.

PMID- 7720939
TI  - The polycystic ovary syndrome: nature or nurture?

PMID- 7720940
TI  - Prospective randomized double-blind trial of 3 versus 6 months of nafarelin
      therapy for endometriosis associated pelvic pain.
AB  - OBJECTIVES: To determine the effectiveness of a 3-month course of nafarelin and,
      furthermore, to determine the long-term efficacy in patients treated for 3 and 6
      months with nafarelin for symptoms associated with endometriosis. DESIGN: Double
      blind, prospective, multicenter, clinical trial. SETTING: Fifteen reproductive
      endocrine clinics throughout the United States. PATIENTS: One hundred seventy
      nine women with pelvic pain and endometriosis. INTERVENTIONS: Patients were
      assigned randomly to 3 months nafarelin followed by 3 months of placebo (n = 91)
      or to 6 months nafarelin (n = 88) in a prospective, randomized, double-blind
      multicenter trial. Patients were followed for 12 months after cessation of
      therapy. MAIN OUTCOME MEASURES: Patient-reported pain scores and physician
      reported physical exam findings. RESULTS: Pain scores dropped significantly by
      the end of treatment in both groups. Symptoms recurred in both groups, and pain
      scores gradually increased during the follow-up period but always remained below
      baseline in both groups. No significant difference in efficacy was noted between
      the groups. A total of 26% of patients in each group underwent retreatment for
      recurrent symptoms. CONCLUSIONS: A 3-month course of nafarelin provided effective
      symptom relief for endometriosis. One year follow-up demonstrated continued pain
      relief but with gradual return of symptoms.

PMID- 7720941
TI  - Combination gonadotropin-releasing hormone agonist and oral contraceptive therapy
      improves treatment of hirsute women with ovarian hyperandrogenism.
AB  - OBJECTIVE: To determine if combination GnRH agonist (GnRH-a) and oral
      contraceptive (OC) therapy was more effective than GnRH-a or OC alone in the
      treatment of hirsute women with ovarian hyperandrogenism. DESIGN: Thirty-three
      hirsute women (ages 15 to 39 years) were randomized into three groups: 3.75 mg IM
      leuprolide acetate (LA) depot every 28 days for 6 months, combination monophasic
      oral contraceptive for 6 months (OC), or GnRH-a plus OC for 6 months (LA + OC).
      MAIN OUTCOME MEASURES: Comparative studies of changes in hormonal and hair
      parameters were performed at baseline, 3, and 6 months after starting therapy.
      RESULTS: After 6 months, serum T and LH levels were decreased significantly in
      all groups although reduction was greater in GnRH-a groups than OC alone. The
      reduction of free T was significantly greater with LA + OC compared with LA or OC
      alone. This could be a consequence of the significant rise in sex hormone-binding
      globulin (SHBG) in LA + OC and OC groups compared with LA in which there was no
      change in SHBG. Reduced facila hair density and decrease in hirsutism score was
      observed in both GnRH-a groups after 6 months. CONCLUSION: "Add-back" OC therapy
      used in combination with a GnRH-a increases SHBG and more effectively lowers free
      T levels in women with ovarian hyperandrogenism. Enhanced suppression of
      "bioavailable" androgens with combined GnRH-a and OC therapy failed to improve
      significantly the therapeutic effect of GnRH-a treatment alone on hirsutism.

PMID- 7720942
TI  - Evaluation of the reproductive performance of women with elevated day 10
      progesterone levels during ovarian reserve screening.
AB  - OBJECTIVES: To evaluate the relationship of elevated day 10 P levels (> or = 1.1
      ng/mL, conversion factor to SI unit, 3.18) during ovarian reserve screening and
      reproductive performance. DESIGN: Prospective screening with longitudinal follow
      up. INTERVENTIONS: One hundred seven women underwent ovarian reserve screening
      with a clomiphene citrate challenge test. MAIN OUTCOME MEASURES: Serum FSH, LH,
      and E2 levels were determined on cycle day 3 and FSH, LH, and P levels were
      determined on day 10. A fertility evaluation was completed and a treatment plan
      was instituted. RESULTS: Twenty-two of 107 (20.6%) women had day 10 P levels > or
      = 1.1 ng/mL. Women with elevated day 10 P levels were similar in age to women
      with normal day 10 P levels (< or = 0.9 ng/mL) but had significantly shorter
      menstrual cycles, higher day 3 and day 10 FSH levels, higher day 3 E2 levels, and
      higher day 10 LH levels than women with normal day 10 P levels. During ovarian
      hyperstimulation, women with elevated day 10 P levels required more ampules of
      hMG, had lower peak E2 levels, and had fewer mature follicles than women with a
      normal day 10 P level. Sixteen of 85 (18.8%) women with normal day 10 P levels
      became pregnant, but none of the 22 women with elevated day 10 P levels became
      pregnant. The incidence of diminished ovarian reserve was higher in women with
      elevated day 10 P levels (13/22; 59%) when compared with women with a normal day
      10 P levels (9/85; 10.6%). CONCLUSIONS: Elevated day 10 P levels (> or = 1.1
      ng/mL) during ovarian reserve screening is associated with diminished ovarian
      reserve and correlates with menstrual cycle parameters associated with a short
      follicular phase and poor reproductive performance.

PMID- 7720943
TI  - Estrogen and progesterone receptors of the out-of-phase endometrium in female
      infertile patients.
AB  - OBJECTIVE: To examine the role of steroid hormone receptor compartmentalization
      in infertile women with "in-phase" or "out-of-phase" endometrium. DESIGN:
      Nonrandomized prospective clinical study. SETTING: A university clinic. PATIENTS:
      Twenty-nine infertile patients without evidence of endometriosis, tubal factor,
      male factor, galactorrhea, or hyperandrogenism were enrolled. Sixteen patients
      had in-phase endometrium and a P level > or = 10 ng/mL (conversion factor to SI
      unit, 3.18) (group A). Four patients had out-of-phase endometrium and a P level >
      10 ng/mL (group B). Four patients had in-phase endometrium and a P level < 10
      ng/mL (group C), and five patients had out-of-phase endometrium and a P level <
      10 ng/mL (group D). MAIN OUTCOME MEASURES: Each patient underwent determination
      of serum P and endometrial sampling on postovulatory days 6 to 9 based on serum
      LH measurement. Dating according to endometrial histology and biochemical
      assessment of estrogen receptor (ER) and P receptor (PR) were performed on each
      sample. RESULTS: The level of cytosol ER was significantly lower in out-of-phase
      endometrium regardless of serum P level. There were no significant differences in
      the levels of cytosol PR and nuclear ER and PR among groups. In a long-term
      follow-up study, 6 of 29 patients became pregnant. The cytosol ER:PR ratio in
      these patients was found to fit a single straight regression line (y = 0.34x -
      2.2). CONCLUSION: Out-of-phase endometrium probably depends on inadequate cytosol
      ER. An appropriate cytosol ER:PR ratio may be important to become pregnant.

PMID- 7720944
TI  - Screening of the mutations in luteinizing hormone beta-subunit in patients with
      menstrual disorders.
AB  - OBJECTIVE: To evaluate the clinical significance of the LH consisting of a mutant
      beta-subunit (Trp8 to Arg8 and Ile15 to Thr15). DESIGN: Clinical and biochemical
      studies. SETTING: Fertility center at the University Hospital and its research
      laboratory. PATIENTS: Fifty-one patients with menstrual disorders and three
      homozygote cases and two heterozygote cases of the mutant LH who were reported
      previously. INTERVENTIONS: Nucleotide mutations of the LH beta gene in patients
      with menstrual disorders were screened using techniques of the polymerase chain
      reaction and restriction fragment length polymorphism. Immunologic and biologic
      activities of the mutant LH and endocrinologic profiles in the affected women
      were evaluated. MAIN OUTCOME MEASURES: Serum LH levels measured with different
      immunoassay kits; serum FSH and LH on the GnRH test; serum thyroid-stimulating
      hormone, PRL, T, and androstenedione; ultrasound examination of the ovaries;
      clinical hyperandrogenic symptoms; and biologic activity of LH. RESULTS: Two
      cases of homozygotes and four of heterozygotes affected by the LH beta gene
      mutations were discovered in the current study through screening of patients with
      menstrual disorders. Serum LH levels in the homozygote cases were undetectable
      using a LH immunoassay kit, whereas levels in the heterozygote cases showed
      reduced detectability with the kit. However, the ratio of the mutant LH values in
      the bioassay to those in the immunoassay was higher in the homozygote group than
      that in the control subjects. Response patterns of serum gonadotropins to GnRH in
      the homozygote were similar to those in patients with polycystic ovary syndrome.
      CONCLUSION: The mutations of LH beta-subunit might be related to menstrual
      disorder in some patients.

PMID- 7720945
TI  - Exogenous melatonin enhances luteinizing hormone levels of women in the
      follicular but not in the luteal menstrual phase.
AB  - OBJECTIVE: To investigate the effect of exogenous melatonin on LH pulsatility in
      women during the follicular and luteal menstrual phases. DESIGN: Randomized,
      double-blind placebo-controlled study. PATIENTS: Normal cycling young women (25
      to 35 years old). INTERVENTIONS: Each subject was admitted at the Clinical
      Research Center for 2 consecutive days on both the follicular and the luteal
      menstrual phases. On each day, at 7:00 A.M. an indwelling catether was placed in
      an antecubital vein for a 10 minutes blood sampling from 9:00 A.M. to 5:00 P.M.
      On the 2 consecutive days of both the follicular and the luteal menstrual phases,
      each subject randomly received either placebo or melatonin pills (1 mg at 8:00
      and 0.75 mg at 10:00 and 12:00 A.M.). MAIN OUTCOME MEASURE: Luteinizing hormone
      pulsatility. RESULTS: The amplitude of LH pulses and mean LH levels were
      increased by melatonin in the follicular but not in the luteal menstrual phase.
      CONCLUSIONS: The stimulatory effect of exogenous melatonin on LH is modulated by
      the endocrine environment and selectively exerted in the follicular phase of the
      menstrual cycle.

PMID- 7720946
TI  - Clinical performance assessment using standardized patients: a primer.
AB  - The clinical performance assessment (CPA) exam using standardized patients is
      being used with increasing frequency in medical education. A standardized patient
      (SP) is an individual who has been taught to portray a patient problem in a way
      that does not vary from student to student. These exams usually take the format
      of the Objective Structured Clinical Examination (OSCE), comprised of short
      "stations" designed to assess a discrete skill, or the simulated clinical
      encounter (SCE), where stations are fewer in number but of longer duration. While
      both formats have a place in student assessment, they measure different skills.
      CPAs have been found to be both reliable and valid. Longer tests tend to be more
      reliable than short ones, and raters and case specificity are the most likely
      factors in lowering reliability in SP-based exams. Validity studies have found
      differences in performance in expected directions and correlations between scores
      on SP-based exams and other measures. Work on developing standard-setting
      procedures is being done. Both the OSCE and SCE formats have application for
      family medicine education. Basic skills and higher-level thinking can be assessed
      and learning prescriptions developed, but some concepts, such as continuity of
      care, are difficult to evaluate. Collaborative efforts among family medicine
      educators should be encouraged.

PMID- 7720947
TI  - Results from the use of a 3-year computer competency curriculum in a family
      practice residency.
AB  - BACKGROUND: Computer competency is becoming essential to practicing family
      physicians. However, no published computer curricula exist for family practice
      residents. METHODS: A computer competency curriculum was designed, implemented,
      and evaluated. Computer software was divided into four categories: patient care,
      education, practice management, and hospital resources. Competency was measured
      and recorded by faculty. The residents evaluated the adequacy and relevance of
      the curriculum to their current and future needs using a questionnaire. RESULTS:
      Competency testing revealed that residents uniformly achieved competency but at
      different rates. Residents rated the quality and quantity of instruction in
      patient care programs highest and in practice management lowest. The usefulness
      of patient care programs was perceived as high during residency but was expected
      to be less useful after residency. In contrast, the usefulness of practice
      management programs was rated as low during residency but expected to be high
      after graduation. Education and hospital programs were intermediate. Self
      assessment indicated that computer use increased during residency; 90% of
      residents characterized themselves as frequent users. CONCLUSIONS: Despite
      logistical problems, teaching computer literacy is a responsibility of physician
      educators. A curriculum must be continually evaluated to ensure that it remains
      current and relevant to the needs of the residents.

PMID- 7720948
TI  - Evaluation of a community-oriented primary care workshop for family practice
      residents in Jerusalem.
AB  - BACKGROUND: A workshop on community-oriented primary care (COPC) has been
      integrated into Hebrew University's family practice residency program for several
      years. The participants of the first three workshops did an evaluation to assess
      subsequent application of the COPC approach. METHODS: The main objectives of the
      45-hour workshop are: a) to learn the principles and practice of COPC as
      illustrated by the Hadassah Community Health Center programs, and b) to learn
      skills required in the COPC programs' various stages of development. In the
      workshop, physicians are required to work in groups of 5-6 to carry out the
      planning of COPC programs, which will be implemented in their practices. A
      structured questionnaire was sent 2-4 years after workshop completion to each of
      the 45 physicians who participated in these workshops. RESULTS: Thirty-six of the
      45 physicians responded to the questionnaire. Of the 36 respondents, 75% reported
      that the content of the workshop was relevant to their daily work. Eighty percent
      of the physicians who were involved in intervention programs reported that
      participation in the workshop improved their ability to plan community programs.
      Fifty-five percent of the respondents reported the application of elements
      learned in the workshop to their current work, mainly in the performance of three
      COPC functions: definition of the community, identification of health problems,
      and planning community health interventions. Few (28%) were involved in
      evaluation measurements. CONCLUSIONS: A COPC workshop characterized by work
      groups of family physicians, epidemiological analysis of their practices' data,
      and the planning of a community program in their communities was positively
      evaluated according to the reported application of COPC functions by family
      physicians and residents in their daily work.

PMID- 7720949
TI  - Residents' formal knowledge acquisition and preferred learning styles.
AB  - BACKGROUND: Many family practice residency programs use the Myers-Briggs Type
      Indicator (MBTI) in their educational programs. Our purpose was to study the
      relationship between learning style, as determined by MBTI personality
      preferences, and residents' cognitive knowledge acquisition, measured by in
      service training examination (ISTE) scores during the first and third years of
      residency. METHODS: We evaluated 36 residents using both their first- and third
      year ISTE composite scores and their MBTI scores. ISTE scores were analyzed
      according to the MBTI personality factors. We used the Wilcoxon Rank-Sum Test to
      determine the association between the improvement in residents' ISTE scores
      between the first- and third-year examinations and preferred learning styles.
      RESULTS: Significant differences were found on the composite ISTE scores for the
      thinking/feeling and judgment/perception scales. Feelers increased ISTE scores
      more than thinkers (P = .031); judgers increased ISTE scores more than perceivers
      (P = .04). CONCLUSIONS: Results do not support the literature or current MBTI
      learning theory. Intuitive residents demonstrated no advantage over sensing
      residents. Residents using feeling/judgment as their preferred learning style
      acquired more knowledge over 3 years than their thinking/perceiving counterparts,
      as measured by ISTE scores.

PMID- 7720950
TI  - A practical tool for community-oriented primary care community diagnosis using a
      personal computer.
AB  - BACKGROUND AND OBJECTIVES: Community-oriented primary care (COPC) is considered
      an attractive concept by many but has had limited implementation due to a lack of
      practical methodology. An important step in COPC is assessment of a community's
      health status, using health indicators as one means of assessment. Currently,
      there is no easy way to combine these indicators and examine their distribution
      over a community. This study analyzed a process for doing that by using a
      personal computer. METHODS: For the community studied, all available community
      based health indicators were identified. A process for combining these
      indicators, using commonly available database and spreadsheet software, was
      developed and analyzed for cost, clinical utility, and problems encountered.
      RESULTS: Problems were encountered with collecting and combining some data, but a
      clinically useful tool was produced. Costs, including purchase of all software
      (with mapping software), were $1,500-$2,000. CONCLUSIONS: With efforts to reduce
      the initial costs, this is a practical and clinically useful tool for viewing the
      geographic distribution of community health indicators. Such practical
      methodology is essential for COPC development.

PMID- 7720951
TI  - Use of decision analysis in a family practice residency for a patient with an
      abdominal aortic aneurysm.
AB  - BACKGROUND: A patient at the Tatem-Brown Family Practice Center with many medical
      problems asked for advice about elective surgical resection of a large abdominal
      aortic aneurysm. METHODS: The best course of action was not obvious, so a
      decision tree was constructed using data from the medical literature and the
      patient's rating of several quality of life issues. RESULTS: Elective surgery was
      the optimal choice for this patient, but the decision was sensitive to values
      chosen for two variables in the decision model. CONCLUSION: Decision analysis has
      benefits in a family practice residency. Residents become familiar with vigorous
      literature review and decision-analytic tools and principles. They gain a deeper
      knowledge of the patient, due to the need to understand the patient's relative
      values for potential outcomes of medical intervention.

PMID- 7720952
TI  - The courage of our convictions: family medicine at the cutting edge of
      scholarship.

PMID- 7720953
TI  - More community, less hospital.

PMID- 7720954
TI  - Commonly asked questions about Family Medicine.

PMID- 7720955
TI  - American Society for Biochemistry and Molecular Biology. San Francisco,
      California, May 21-25, 1995. Abstracts.

PMID- 7720956
TI  - [A cross-sectional epidemiological study of symptoms and respiratory physiology
      in a sample of workers in shoe manufacture].
AB  - The prevalence of respiratory symptoms and functional abnormalities has been
      evaluated in a sample of 350 workers (186 males and 164 females, mean age: 35.1
      and 36.6 years respectively) employed in 24 factories of the shoes industry in
      the area of Pisa, exposed to airway irritants (solvent vapours, leather dusts and
      fumes). Each subject performed C.N.R. questionnaire of respiratory symptoms and
      diseases, and measurement of Forced Vital Capacity and derived indices. A mild
      prevalence of respiratory symptoms (chronic cough: 9.3% and 8.5% in males and
      females respectively; chronic phlegm: 14.6% and 6.8%; persistent wheeze: 2.1% and
      1.7%; dyspnea of 1st degree: 23.3% and 39.0%) was reported, more frequently in
      smokers than in non smokers. Subjects with longer job duration in the shoe
      industry showed a trend to have a higher prevalence of chronic phlegm than
      subjects with shorter job duration; on the contrary, the last ones had a higher
      prevalence of rhino-conjunctivitis. A higher prevalence of attacks of shortness
      of breath and dyspnea of 2nd degree in males, and dyspnea of 1st degree in
      females was observed in workers to high risk job (to shear, to use adhesive,
      etc.) with respect to workers employed in low risk job (to assembly, to store
      etc). Mean spirometric values where in the normal range. Subdividing the subjects
      in groups with different smoking habit and job duration, a mild effect of the
      occupational exposure in groups with the same smoking habit could be observed for
      FEV1 and MEF50 particularly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720957
TI  - [The inhalation of low concentrations of manganese powders produces changes in
      respiratory mucociliary clearance].
AB  - The aim of this study is to verify whether inhaling metallic dusts, containing a
      lower concentration of Mn (as Mn3O4) than current TLV can cause alterations in
      exposed workers tracheobronchial mucociliary clearance. We studied 20 grinders
      using an 11.5-13% Mn steel, and a control group of 21 standard steel grinders,
      employed in the same foundry. Environmental Mn dust was measured by personal
      samplers. All workers were administered a questionnaire about chronic bronchitis;
      the following examinations were also carried out: medical examination,
      spirometry, chest standard X-ray and urinary Mn dosage. Mucociliary clearance was
      measured by human respiratory mucus transportability on frog palate and expressed
      as normalized frog palate transport rate (NFPTR). Mucus was obtained through a
      sputum so protected as to avoid salivary contamination. Environmental
      measurements showed a Mn concentration from 0.1 to 1 mg/m3 with respect to a TLV
      of 5 mg/m3. Exposed workers and control group were homogeneous as far as age,
      working period, tobacco smoking habit and spirometric parameters are concerned.
      Chest X-ray examination showed no evidence of pneumoconiosis. Mn exposed workers
      showed a NFPTR reduction, if compared to normal level (0.70). NFPTR average value
      in exposed group has come out to be much lower than in control group. NFPTR
      alteration in Mn exposed group appears to be strictly linked to a longer than 15
      years working seniority. Urinary Mn values resulted extremely low in each worker
      and their average was not significantly different between the groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7720958
TI  - Occupational asthma: fate and management after the diagnosis.
AB  - The clinical and socio-professional fate of subjects with occupational asthma is
      not univocal. We re-examined twenty-nine subjects diagnosed in our center as
      suffering from this disease an average 14 months, SE 1.54 after the diagnosis. At
      the follow-up examination each patient underwent interview, spirometry and
      methacholine challenge, 18 patients (group A) had ceased exposure to the
      sensitizing agent but among them only 7 had been relocated in another area of the
      plant, the others had resigned or retired. The other patients had not changed
      workplace, 7 (group B) having had intermittent exposure to the offending agent
      and 4 (group C) having continued to be exposed daily. At the follow-up
      examination only 9 patients were asymptomatic, each of them belonging to group A,
      whereas in the other 9 of the same group symptoms persisted, although reduced. In
      group B and C all patients were still symptomatic and required pharmacologic
      treatment. Within group A patients who became asymptomatic had shorter duration
      of symptoms before diagnosis (12.9 months, SE 6.4 vs 23.9, SE 9.7), higher FEV-1
      (96.1, SE 6.7 vs 86.9, SE 5.6) and PD20FEV-1 (1773.4 micrograms, SE 590 vs 730.8,
      SE 295) at the time of the diagnosis and showed a significant (p < 0.01) increase
      in FEV-1 (from 96.1, SE 6.2 to 101.6, SE 5.5) and a tendency to decrease in
      bronchial reactivity to methacholine at the follow-up examination. At the time of
      the follow-up examination only 5 out of 29 patients (17.2%) had been contacted by
      the compensation board.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720959
TI  - [A new environmental pathology: styrene-induced rhinitis].
AB  - We describe the case of a 36 ys aged woman complaining of symptoms of
      oculorhinitis with itching, occasional dyspnea and laryngeal constriction. The
      patient related her symptoms with the emission of dusts and steam from a factory
      in the neighbourhood producing manufactures using polyester resins dissolved in
      styrene. No bronchospastic response was obtained after challenge with methacoline
      and ultrasonic nebulization of distilled water, which instead provoked a
      significant increase of nasal resistance. The inhalation challenge with styrene
      produced a dual nasal response. To our knowledge this is the first case of non
      occupational neighbourhood rhinitis provoked by styrene.

PMID- 7720960
TI  - [Occupational pathologies: prevention (the realization of nonharmful productive
      technologies) and protection (standards and methodology) in the identification of
      work-related causes].
AB  - Protection at work should be intended as the whole measures which tend to study
      and improve the relationship between the individual and the work environment. A
      satisfactory work is important fos psychic health: it gives gratifications and
      may induce sense of personal fulfillment. The application of preventive safety
      rules can only reduce or limit, but never annul, the occurrence of dangerous
      events even if all the work safety rules are strictly enforced and observed.
      Stress factors in working environment are listed in the text. For tumours it is
      often necessary to apply to more or less consolidate, though sometimes debatable,
      presumptive criteria in the identification of casual relation. The identification
      of the connection with work implies the necessity to consider causal relations
      between work factors and diseases. Nature, modality of work and work conditions
      in which the worker acts: risk connected to the above mentioned conditions and
      probability for detrimental events to occur. Influence of environmental
      characteristics on the risk of occurrence of tumours and the problem of the
      relations between tumour and subject are discussed. Direct invasiveness of
      neoplastic tissue is related to alterations of the immunologic control and
      functional remote alterations caused by the tumour itself. Tumour illness is a
      general phenomenon, conditioned by tissue specific and immunological
      modifications. Relation between cranial traumas and tumour needs all the elements
      collected during the study of the case reported to be evaluated. Exploitation of
      every single element must be evaluated with a supple mind. There is need for
      rules which more rigorously regulate and control the hazards in the work
      environment.

PMID- 7720961
TI  - [The diagnosis of occupational hand-arm syndromes. 1. The state of the art].
AB  - Alterations of the microcirculation are, at our latitudes, the most common distal
      manifestations of the hand-arm syndrome, and of a number of other work-related
      diseases. Diagnostic investigations aimed at providing documentary evidence for
      microvascular damage or disfunction are, therefore, of particular importance.
      This paper discusses the currently available diagnostic approaches for
      professional acrosyndromes. The biohumoral alterations associated with cold
      induced angiospasm are also described, but their diagnostic utilization is not
      recommended. The technical aspects of the "cold tests", as well as its advantages
      and drawbacks, are finally presented. On the basis of a personal experience with
      over 4.500 subjects, the authors conclude that, in the field of prevention,
      digital volumetric pulse plethysmography in association with the "cold test"
      should be adopted to evaluate the worker fitness for specific tasks.

PMID- 7720962
TI  - [Oncogenes as indicators of occupational exposure to carcinogenic agents].
AB  - Oncogenes are a class of genes capable of inducing neoplastic alterations of the
      cell. Recently, oncogenes have received greater attention in environmental
      medicine, since they may be useful tools for monitoring individuals exposed to
      carcinogenic chemicals. Their potential use as biomarkers is supported by studies
      indicating changes in the expression of growth factors and oncoproteins in
      chemically induced cancer. These alterations may even take place prior to
      clinical diagnosis. In addition, availability of new immunoblotting techniques,
      which allow the detection of oncoproteins and growth factors in easily accessible
      tissues, such as serum and urine, has provided promising preliminary results in
      humans. In this paper, mechanisms of oncogene activation and their role in
      occupational carcinogenesis are briefly discussed. Recent human studies
      suggesting a link between occupational toxicants and oncogenes, as well as a
      potential use of oncogenes as biomarkers, are also reported. Finally, advantages
      and limits of oncogenes over more traditional biomarkers are discussed.

PMID- 7720963
TI  - [Chronic progressive obliterating arteriopathy and muscle fatigue: the role of
      frequency analysis of the electromyographic signal].
AB  - Clinical evaluation of patients with peripheral arterial disease (PAD) is mainly
      based on Fontaine's classification, in which pain is the most important element.
      The use of objective techniques can allow a more precise evaluation, since pain
      is always subjective. In PAD patients, pain is frequently associated with early
      fatigue. Peripheral muscle fatigue can be easily assessed by a particular
      electromyographical method, based on the frequency analysis of the signal. In PAD
      patients, this method can provide objective information on muscular performance,
      with possible uses in medicine, surgery, rehabilitation and occupational
      medicine.

PMID- 7720964
TI  - [Telethermographic effects and a comparative clinical assessment of the treatment
      of shoulder periarthritis using ultrasound].
AB  - The aim of this study was the instrumental evaluation of ultrasound therapy in
      patients with periarthritis of the shoulder, with regard to studies that show
      doubts about the real effectiveness of the antiinflammatory action of ultrasound.
      Two groups of subjects were studied, periarthritis versus normal patients.
      Clinical evaluation and instrumental measures (telethermography) were performed
      before and after ultrasound therapy. These data were statistically analyzed and
      constant variations were found, according to clinical evaluation of the patients.
      Therefore results of this study demonstrated a real influence of ultrasound
      therapy on periarthritis of the shoulder.

PMID- 7720965
TI  - [Oxyuriasis: its indoor transmission correlated with crowding in housing].
AB  - In two different human settings in the province of Pavia, Italy, statistically
      significant correlations were found between socioeconomic level of the families
      or crowding in the houses, and prevalence of oxyuriasis in schoolchildren. An
      indoor transmission is postulated.

PMID- 7720966
TI  - [The risk from mixtures in the indoor air].
AB  - Indoor air is typically contaminated by complex mixtures of several pollutants at
      low concentrations. As a consequence, the application of methods for evaluating
      the effects of multiple exposure should be recommended for risk assessment of
      indoor air pollutants. For this purpose, criteria recommended by scientific and
      governmental Institutions for risk assessment of multiple indoor exposure are
      reported.

PMID- 7720967
TI  - [Indoor pollution: a report of 2 clinical cases of occult carbon monoxide
      poisoning].
AB  - A large part of the general population is potentially exposed to excessive
      concentrations of carbon monoxide (CO), both in the domestic and work
      environment. Beside acute, often fatal poisoning, the possibility of occult
      intoxication should be considered; this condition can affect people who are often
      unaware of the existence of a toxic exposure in their homes or work places. We
      describe two non-smoking patients, husband and wife, 53 and 57 years old,
      respectively, who suffered cephalea, nausea and neurobehavioural disturbances
      during a period of approximately one year; these symptoms were reported to
      improve or disappear on several occasions during the patients' absence from home.
      Careful anamnesis suggested a protracted exposure to nonlethal concentrations of
      CO contaminating the patients' bed-chamber from the misfunctioning flue of the
      heating system. It was not possible to measure carboxyhaemoglobinemia until
      approximately 24 hours since the last presumptive exposure. The levels found were
      therefore relatively low (4-5%), yet higher than the reference values for normal
      non-smoking subjects. Carboxyhaemoglobin concentrations almost returned into the
      normal range during the period of hospitalization. These two cases exemplify how
      low level CO exposure may cause aspecific pathological manifestations that are
      often misdiagnosed or overlooked.

PMID- 7720968
TI  - Needs and requirements for undergraduate and graduate training in environmental
      and occupational epidemiology.
AB  - Training in modern medicine aims at teaching not only the structure and function
      of the human organism in health and in disease, but also it aims at revealing the
      factors responsible for human health. The second field of teaching is based
      mainly on epidemiology. In undergraduate teaching, the epidemiological training
      should be introduced as early as possible in the curriculum and possibly divided
      into two parts, theoretical and practical. With the increasing awareness that the
      maintenance of health in populations is an ecological problem, there is also a
      growing need for professional epidemiologists who could assist in recognizing
      health risks, assessing and developing prevention strategies and in arranging of
      health services in a responsible way. The objectives of graduate teaching in
      epidemiology are different from those of undergraduate teaching. The graduate
      teaching should cover not only professional epidemiologists but also should be
      addressed to health services administrators, clinicians and graduates from other
      specialists and paramedical and auxiliary personnel. The needs and requirements
      for teaching epidemiology in undergraduate and postgraduate levels have been
      discussed against the background of currently available courses in Europe and
      local perception of environmental and occupational problems in European
      countries.

PMID- 7720969
TI  - [Audiometry in the cellulose industry].
AB  - A noise level dosimetry and audiometric testing were conducted in a cellulose
      factory to determine the hazardous noise level and the prevalence of noise
      induced hearing loss among the exposed workers. The noise level was recorded up
      to 90 db (A) in several working areas. 18 workers, potentially exposed to noise
      injury, evidenced a significant hearing loss. While no evidence of noise injury
      was recorded in a control group of 100 subjects. This finding suggest a strict
      relationship between audiometric tests, the noise level recorded in the working
      place and the working seniority of exposed employers.

PMID- 7720970
TI  - [Partial regression of Barret esophagus with high grade dysplasia and
      adenocarcinoma after photocoagulation and endocurietherapy under antisecretory
      treatment].
AB  - Barrett's oesophagus is a premalignant condition. The possibility of eradicating
      at least partially the metaplastic epithelium has been reported recently. In this
      case report, a patient with Barrett's oesophagus complicated by high grade
      dysplasia and focal adenocarcinoma was treated by Nd:Yag laser then high dose
      rate intraluminal irradiation while on omeprazole 40 mg/day. A partial
      eradication of Barrett's oesophagus and a transient tumoural regression were
      obtained. Histologically, residual specialized-type glandular tissue was observed
      beneath regenerative squamous epithelium. Four months after intraluminal
      irradiation, a local tumoural recurrence was detected while the area of restored
      squamous epithelium was unchanged on omeprazole 40 mg/day. This indicates that
      physical destruction of Barrett's oesophagus associated with potent antisecretory
      treatment can induce a regression of the metaplastic epithelium, even in presence
      of high grade dysplasia. The persistence of specialized-type glands beneath the
      squamous epithelium raises important issues about its potential malignant
      degeneration.

PMID- 7720971
TI  - Hypersensitivity to azathioprine mimicking gastroenteritis. Absence of recurrence
      with 6-mercaptopurine.
AB  - Hypersensitivity mimicking gastroenteritis is a rare complication of azathioprine
      therapy for which the mechanism is unknown. We report a case of devastating
      diarrhoea and vomiting due to azathioprine treatment in which hypersensitivity to
      the imidazole moiety of azathioprine was demonstrated. This has important
      therapeutic implications: in this situation, 6-mercaptopurine, which is the
      portion of azathioprine responsible for the cytotoxic therapeutic effect, can be
      administered without recurrence of side-effects.

PMID- 7720972
TI  - [Simultaneous hepatic cholangiocarcinoma and bone fibrosarcoma 45 years after
      ingestion of Thorotrast].
AB  - This case of a 63 year old man reports the simultaneous development of hepatic
      cholangiocarcinoma and fibrosarcoma of the sacrum 45 years after the systemic
      injection of Thorotrast. The characteristic radiologic aspect was an important
      criteria for diagnosis. Biopsies have confirmed the histology of both tumors. We
      describe the way to thorotrastosis diagnosis and characteristic malignant tumors,
      especially cholangiocarcinoma, induced by Thorotrast.

PMID- 7720973
TI  - [Primary sclerosing cholangitis and systemic lupus erythematosus].
AB  - We report the association of primary sclerosing cholangitis and systemic lupus
      erythematosus in a 39 year-old man. Six months after a diagnosis of primary
      sclerosing cholangitis was established, the patient was hospitalized for a
      pleural effusion and acute pericarditis. Emergency pericardiocentesis, was
      required due to sudden cardiac tamponnade. Plasmatic anti-DNA and anti-nuclear
      antibodies were present. Treatment by steroids greatly improved symptoms. This
      clinical association suggests that some immune disorders may be common to the two
      diseases.

PMID- 7720974
TI  - [Electric analgesia and endoscopic laser treatment: morphinans remain
      indispensable].

PMID- 7720975
TI  - [Efficacy of thalidomide in the treatment of esophageal ulcers in human
      immunodeficiency virus infection].

PMID- 7720976
TI  - [Bilateral hemorrhagic necrosis of the adrenal glands in antiphospholipid
      syndrome: diagnostic pitfall and rare cause of acute abdominal pain syndrome].

PMID- 7720977
TI  - [Intolerance to polyethylene glycol].

PMID- 7720978
TI  - [Necrotizing amebic colitis].

PMID- 7720979
TI  - [Obstruction of the bile duct with tumoral fragments in the course of
      intrahepatic biliary cystadenoma].

PMID- 7720980
TI  - [Intraductal biliary metastasis: metastasis of a metastasis?].

PMID- 7720981
TI  - [Prevalence of markers of hepatitis B and C viruses in mentally handicapped
      adults].

PMID- 7720982
TI  - [Biliary pain after ingestion of paracetamol and codeine].

PMID- 7720983
TI  - [Interferon therapy of chronic hepatitis B in children].

PMID- 7720984
TI  - [Evaluation of the teaching of echo-endoscopy. Application to the assessment of
      invasiveness of cancer of the esophagus and the cardia].
AB  - OBJECTIVES: Learning endosonography (EES) is known to be difficult, and the
      theory must be understood before performing EES routinely. The aim of the study
      was to evaluate the diagnostic indexes of EES in the staging of cardio
      oesophageal cancer after a period of theoretical apprenticeship of EES and a
      learning period in a centre experienced in EES since 1989. METHODS: Five
      observers, having never used EES, followed to EES examinations for a 3-6 month
      period. They then reviewed the standardized records of 29 patients with cardio
      oesophageal cancer. They had to evaluate the degree of tumour infiltration within
      oesophageal wall and the site of metastatic lymph nodes. Results were compared
      with the diagnosis of 5 experienced senior endoscopists. Interobserver agreement
      was estimated with kappa statistics and considered excellent for k > or = 0.75,
      good to moderate if 0.75 > k > or = 0.40, and poor if k < 0.40. RESULTS: Inter
      observer agreement was poor for the topographic diagnosis of lymph nodes (kappa
      index from -0.09 to 0.33), lower to that of the 5 senior observers (0.33 to
      0.77). It was satisfactory for degree of tumour infiltration (T1: k = 0.66; T2: k
      = 0.58; T3: k = 0.56; T4: k = 0.46). The individual sensitivities were weak
      according to lymph nodes site, but good for presence of lymph nodes (86 to 100%),
      with a specificity of 40 to 73%. CONCLUSIONS: After theoretical training of EES,
      agreement and diagnostic performances are good enough to diagnose pathological
      images (except for T4 tumors), and poor for localizing images in the mediastinum.
      This emphasizes the difficulties in learning echo-anatomy and gives useful
      guidelines for training programs in EES.

PMID- 7720985
TI  - Nitrogen movements in the upper jejunum lumen in humans fed low amounts of casein
      or beta-lactoglobulin.
AB  - OBJECTIVES AND METHODS: To compare the progression of milk proteins in the upper
      part of the digestive tract, gastro-jejunal nitrogen movements were studied in 6
      healthy human volunteers after beta-lactoglobulin and casein ingestion. 400 mL of
      water (control), purified beta-lactoglobulin (20 g/L) or casein (20 g/L), each
      adjusted to 25 microCi with 14C-polyethylene glycol, were given per os. Samples
      were collected in the stomach and 20 cm below the Treitz ligament every 20 min
      for 2 hours and measured for volume, osmolarity, ions and nitrogen content.
      RESULTS: The jejunal flow rate peaked in the 0-20 min period following water and
      beta-lactoglobulin ingestion, and in the 20-40 min period after casein ingestion.
      The gastric half-emptying time (T1/2 min) of the liquid phase was significantly
      different (P < 0.05) for water (12.1 +/- 0.8), beta-lactoglobulin (14.5 +/- 3.3)
      and casein (26.5 +/- 9.3). Before ingestion of the test meals, the basal rate of
      nitrogen was 9.14 +/- 4.09 mmol/h in the jejunum. The total nitrogen content in
      the jejunum peaked significantly in the 0-20 min period after beta-lactoglobulin
      ingestion and the 20-40 min period after casein ingestion. The apparent gastro
      jejunal protein absorption values were 63% for casein and 66% for beta
      lactoglobulin in the 120 min period. CONCLUSIONS: These results show that beta
      lactoglobulin and casein behave differently in the upper part of the digestive
      tract due to different gastric emptying rates.

PMID- 7720986
TI  - [Treatment of acute chemically induced diarrhea by inhibition of enkephalinase.
      Results of a pilot study].
AB  - BACKGROUND AND OBJECTIVES: Acute chemotherapy-induced diarrhoea may require
      reducing or even stopping subsequent therapy. Antidiarrhoeal drug efficiency has
      not been extensively studied and the effects of the new antisecretory compound
      acetorphan--a potent enkephalinase inhibitor active in acute diarrhoea--are
      unknown. The aim of this study was to investigate the possible effects of
      acetorphan on 5 FU-induced diarrhoea in man. MATERIAL AND METHODS: Fifteen
      patients reporting acute diarrhoea following chemotherapy were included in this
      study. They presented with metastatic colo-rectal cancer (n = 14) or pancreatic
      carcinoma (n = 1) and were treated, once weekly, by an 8-hour IV infusion of
      folinic acid 200 mg/m2 and 5 FU 1,800 to 3,000 mg/m2. In each patient, number and
      consistency of stools were assessed every day during the week following
      chemotherapy, once without (control period) and once with acetorphan p.o. 300
      mg/d/7d. RESULTS: During the control period, 3 out of 15 patients did not have
      significant diarrhoea, but 2 out of 3 patients had abdominal pain which was
      relieved by acetorphan without appearance of constipation. Twelve out of 15
      patients presented with diarrhoea (> 3 stools/day for > 2 days: WHO grades 2 and
      3); with acetorphan, the number of stools per day was reduced in all cases from
      6.3 (range: 3-10.6) to 4.9 (range: 2.6-8.9) (P < 0.002), and the number of days
      with liquid stools dropped from 4.7 (range: 2-7) to 2.4 (range: 0-7) (P < 0.02).
      In addition, during treatment with acetorphan, there was a close positive linear
      relationship between the percent reduction in the number of stools and the number
      of stools during control period up to a 8 stools/day level (8 patients) above
      which efficiency decreased (4 patients). CONCLUSION: These results suggest the
      efficacy of acetorphan on chemotherapy-induced diarrhoea and urgent need for a
      randomized controlled trial.

PMID- 7720987
TI  - [Two types of colonic adenocarcinoma. Arguments and implications].

PMID- 7720988
TI  - [Comparative randomized open study of the efficacy and tolerance of enemas with 2
      gr of 4-amino-salicylic acid (4-ASA) and 1 gr of 5-amino-salicylic acid (5-ASA)
      in distal forms of hemorrhagic rectocolitis].
AB  - OBJECTIVES AND METHODS: The aim of this multicentre, randomized open trial was to
      compare the efficacy and tolerance of 4-ASA vs 5-ASA enemas in the treatment of
      distal moderately active ulcerative colitis. Fifty patients were randomized to
      receive enemas in 100 mL suspension of 4-ASA (2 g, n = 26), or 5-ASA (1 g, n =
      24). The subjects filled a daily questionnaire on enema retention duration, and
      tolerance. Clinical and endoscopic evaluations were performed at baseline and
      after 2 and 4 weeks. RESULTS: Significant clinical and endoscopic improvements
      occurred in both groups. Efficacy and enema retention time did not differ between
      groups. Tolerance was significantly better for 4-ASA: score 0.46 +/- 0.77 vs 1.00
      +/- 0.73, P = 0.03. CONCLUSIONS: Efficacy of both treatments was equivalent, but
      4-ASA enemas were better tolerated than 5-ASA in this open trial.

PMID- 7720989
TI  - [Nitric monoxide (NO), mediator of non-adrenergic non-cholinergic effects of the
      enteric nervous system and esophago-gastric motility].

PMID- 7720990
TI  - [Should chronic hepatitis B in children be treated?].

PMID- 7720991
TI  - [Treatment of chronic viral hepatitis B in children with moderate doses of alpha
      interferon].
AB  - AIM: The alpha interferon treatment criteria have not been established in
      children with chronic hepatitis B. We report the results of a prospective study.
      METHODS: Between 1988-1992 14 children (2 girls and 12 boys) with chronic
      hepatitis B received 3 million U/m2 of interferon alpha three times a week for 6
      months. All patients underwent a liver biopsy that showed a pattern of chronic
      active hepatitis. One patient had cirrhosis. Hepatitis B surface antigen,
      hepatitis Be antigen and hepatitis B virus DNA had been positive in the serum in
      all for at least 6 months and anti-delta antibodies were negative in all.
      Pretreatment aminotransferase levels were at least 1.5 times the upper limit of
      normal. RESULTS: After treatment patients were followed up for at least one year
      (mean: 21.5 +/- 8.3 months). At the end of treatment HBV DNA was negative in 13
      out of 14 patients and reappeared in one; HBeAg seroconversion was observed in 11
      patients with the appearance of anti-HBe antibodies. Six patients lost the HBs
      antigen within 1 to 14 months after treatment. Anti-HBs antibodies did not appear
      in any patients and aminotransferase level normalized in 13 patients. Thirteen
      patients underwent liver biopsy after treatment which showed improvement in 12.
      CONCLUSIONS: Treatment with alpha interferon at doses of 3 MU/m2 is effective in
      children with active hepatitis B. Long-term follow up is needed to evaluate the
      effectiveness of this therapy.

PMID- 7720992
TI  - [Liver steatosis. I: Macrovesicular steatosis].

PMID- 7720993
TI  - [Liver steatosis. II: Microvesicular steatosis].

PMID- 7720994
TI  - [Standardization of echo-endoscopic examinations in digestive cancerology. Club
      Francais d'Echo-Endoscopie Digestive].

PMID- 7720995
TI  - Prospective multicenter evaluation of an initially placed button gastrostomy.
AB  - Eight-six patients were prospectively evaluated following placement of the One
      Step gastric button. Placement problems, most commonly caused by the stoma
      measurement device, were noted in 17%. In an additional 30% of patients,
      peristomal infection, leakage, or migration developed within the first 90 days of
      placement. The authors conclude that although this gastric button can be placed
      in the majority of patients, potential design and placement problems may produce
      significant intraprocedural and postprocedural complications.

PMID- 7720996
TI  - Assessment of sucralfate coating by sequential scintigraphic imaging in radiation
      induced esophageal lesions.
AB  - The value of mucosal protection with sucralfate in cases of gastric ulceration is
      well documented. Although sucralfate is advocated as treatment of esophageal
      lesions, we found it to be of limited value in the management of radiation
      induced esophagitis; in a pilot study of 10 cases, minor relief of symptoms, with
      analgetics still required, was noted in 4 patients, and no improvement was seen
      at endoscopy after 6 weeks of treatment in any patient. To see if this might be
      the result of inadequate mucosal coating, we administered sucralfate labeled with
      technetium 99m to 26 patients with endoscopically proven esophagitis secondary to
      irradiation for esophageal carcinoma. The degree of coating was evaluated
      according to persistence of the radionuclide in the affected esophageal segment.
      Scans were performed at regular intervals for 120 minutes after administration of
      150 MBq 99mTc-sucralfate. Although scans were positive for radioactivity in 24 of
      26 (92%) patients, only 8 (31%) of these represented selective binding of
      sucralfate to tissue. In the other 16 cases, scans were positive for sucralfate
      and albumin, indicating nonspecific retention most likely caused by concomitant
      esophageal stenosis. Residual radioactivity was observed for 30 minutes or more
      in 11 (42%) patients, but scans were positive for radioactivity after 1 to 2
      hours in only 4 (15%). The duration and intensity of tracer accumulation were
      similar in both acute lesions an chronic radiation damage. These findings suggest
      that the inability of sucralfate to alleviate irradiation-induced odynophagia may
      be related to insufficient duration of adherence of this compound to damaged
      esophageal mucosa.

PMID- 7720997
TI  - Observer variation and reproducibility of endoscopic ultrasonography.
AB  - To investigate interobserver variation and reproducibility of endosonographic
      findings, both experienced and inexperienced endosonographers evaluated depth of
      tumor invasion (T stage) and presence of lymph node metastasis (N stage) in 50
      patients with nonobstructing esophageal carcinoma. Results were compared with the
      findings by surgical pathology of the resected specimens. The kappa statistic
      (kappa) was used to assess interobserver and intraobserver agreement and
      consistency of accurate interpretation (reproducibility) for the two groups.
      Agreement between the experienced endosonographers was excellent (kappa = > .75)
      for T1 and T4 lesions, good (kappa = .61) for T3 lesions, but only poor (kappa =
      > .46) for T2 lesions. The overall agreement between the experienced
      endosonographers was equally good for both T and N stages. Agreement between the
      inexperienced endosonographers was poor for all T stages but was good for lymph
      node metastasis (kappa = .52). For experienced endosonographers, endosonographic
      reproducibility of histologically confirmed T4 lesions was excellent, followed
      closely by T3 and T2 lesions; T1 tumors were frequently interpreted differently
      by the same endosonographer. Reproducibility of N stage determinations was
      excellent for N0 lymph nodes and good for N1 nodes. Thus, for experienced
      endosonographers, interobserver agreement was excellent for all T stages except
      T2, whereas reproducibility of determination of depth of tumor invasion was good
      to excellent for T2, T3, and T4 lesions but poor for T1 lesions. As yet poorly
      defined operator and machine-dependent factors that cause misinterpretation of T1
      and T2 tumors will require additional study.

PMID- 7720998
TI  - Hemodynamic effects of prolonged abdominal insufflation for laparoscopic
      procedures.
AB  - Abdominal insufflation for laparoscopic procedures leads to numerous hemodynamic
      effects. We focused on blood flow distribution and arterial and venous pressure
      changes during CO2 insufflation at an intra-abdominal pressure of 12 mm Hg. Three
      segments of the vascular system were investigated (intrathoracic, cranial
      extrathoracic, caudal extrathoracic) in supine animals at insufflation, during a
      90-minute period of pneumoperitoneum, and at desufflation. Except for
      instrumentation of the animals, no further surgery was performed. At insufflation
      (+5 minutes), cardiac output increased from 2.7 +/- 0.5 to 3.3 +/- 1.1 L/min
      while heart rate decreased from 138 +/- 26 to 128 +/- 17 beats per minute.
      Increases in jugular venous (from 6 +/- 1 to 11 +/- 4 mm Hg) and atrial (right,
      from 7 +/- 1 to 12 +/- 3; left, from 12 +/- 4 to 17 +/- 5 mm Hg) pressures
      occurred uniformly during inspiration. The great variance in atrial pressures
      during ventilation was not associated with changes in stroke volume, as the
      effective transmural filling pressures remained nearly constant. The increase in
      femoral venous pressure occurring during both inspiration and expiration (from 10
      +/- 2 to 18 +/- 4 mm Hg) exceeded the increase in right atrial and jugular venous
      pressures during inspiration. Parallel increases were noted in arterial pressures
      (carotid, from 119 +/- 15 to 129 +/- 9; femoral, from 122 +/- 16 to 133 +/- 10 mm
      Hg), left ventricular pressure (from 133 +/- 17 to 143 +/- 10 mm Hg), and carotid
      and femoral flow (carotid, from 174 +/- 71 to 195 +/- 70; femoral, from 66 +/- 25
      to 73 +/- 40 (NS) mL/min).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7720999
TI  - Short- and long-term outcome of esophageal perforation.
AB  - Esophageal perforation is an important complication of endoscopy and dilation,
      but few data are available regarding long-term outcome in these patients. Thirty
      one consecutive patients with esophageal perforation were studied. Long-term
      outcome was determined by office follow-up and questionnaires via mail or
      telephone. The study group included 16 men and 15 women with a mean age of 61 +/-
      4 years. Instrumentation was the principal cause of perforation (77%), and pain
      was the principal symptom in the majority of cases. However, some patients
      reported no pain, their only symptom being shortness of breast or dysphagia on
      swallowing saliva. Contrast examinations were used to establish the diagnosis,
      but results were initially negative in 3 of 27 patients (11%). Seven patients
      were treated nonsurgically (nasogastric drainage, antibiotics, and intravenous
      alimentation). Fourteen patients underwent primary closure of the esophageal
      rent. Six patients underwent surgical drainage, 3 underwent total esophagectomy,
      and 1 died during surgery before the esophagus was exposed. Thirty-day mortality
      was 6.4%. Mean hospital stay was 26 +/- 5 days. Postdischarge follow-up was
      available in 28 of the 29 patients (97%) surviving initial hospitalization, and
      the mean follow-up was 47 +/- 9 months. Nineteen patients had persistent
      dysphagia, and 6 underwent dilation again. One of these patients had a second
      perforation. Contrary to results of some earlier studies, the mortality from
      esophageal perforation was low in our study because of early intervention in
      suspected cases. Results of contrast studies are sometimes negative in the early
      stages after perforation, and studies may need to be repeated.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7721000
TI  - Small nonpolypoid neoplastic lesions of the colon: endoscopic features with
      emphasis on their progression.
AB  - We investigated the endoscopic and histologic features of 74 nonpolypoid
      neoplasias of the colorectum measuring 15 mm or less in diameter.
      Colonoscopically, they were characterized by flat growth, being either slightly
      elevated with a central depression or else completely flat against the
      surrounding mucosa. Of the 54 lesions measuring 5 mm or less in diameter, 3 (7%)
      were diagnosed as cancer, whereas the remaining 51 (93%) were diagnosed as
      adenomas with moderate epithelial atypia. The lesions measuring more than 5 mm
      were fewer in number (20), and they were more frequently given the histologic
      diagnosis of severe epithelial atypia (20%) and cancer (70%). Whereas the
      endoscopic features of the cases of adenoma with moderate atypia included both
      complete flatness and flat-topped elevation with a central depression, the
      lesions diagnosed as adenoma with severe atypia were endoscopically recognized as
      flat or slightly depressed lesions, and a deep central depression or prominent
      elevation was noted in the lesions diagnosed as cancer. These findings suggest
      that some minute nonpolypoid neoplasias may transform to nonpolypoid cancers and
      invade the submucosa, whereas others do not manifest rapid growth.

PMID- 7721001
TI  - A new small probe for ultrasound imaging via conventional endoscope.

PMID- 7721002
TI  - Ultrasound catheter probe-assisted endoscopic cystgastrostomy.

PMID- 7721003
TI  - Optimal intra-ampullary orientation with a pretrained sphincterotome.

PMID- 7721004
TI  - Color Doppler endoscopic ultrasonography for the evaluation of gastric varices
      and endoscopic obliteration with cyanoacrylate glue.

PMID- 7721005
TI  - Laparoscopically assisted panenteroscopy: a feasibility study in pigs.

PMID- 7721006
TI  - Mucosal stripping: a complication of push enteroscopy.

PMID- 7721007
TI  - Obstructive jaundice caused by pancreatic carcinoma in the setting of a normal
      pancreatogram.

PMID- 7721008
TI  - Retrieval of five razor blades from the stomach using a new endoscopic technique.

PMID- 7721009
TI  - Endoscopic removal of granular cell tumors.

PMID- 7721010
TI  - Early adenocarcinoma arising from ectopic gastric mucosa in the cervical
      esophagus.

PMID- 7721011
TI  - Current management of severe lower gastrointestinal bleeding.

PMID- 7721012
TI  - Pediatric endoscopy, deep sedation, conscious sedation, and general anesthesia-
      what is best?

PMID- 7721013
TI  - Limitation of histology for detecting Helicobacter pylori.

PMID- 7721014
TI  - Endoscopic replacement of PEG.

PMID- 7721015
TI  - Carcinoma arising in gastric hyperplastic polyps.

PMID- 7721016
TI  - Endoscopic clip assisted placement of enteral feeding tubes.

PMID- 7721017
TI  - Nasoenteric tube placement using Savary-Gilliard guide wire for postoperative
      gastric retention following transhiatal esophagectomy.

PMID- 7721018
TI  - Umbilical metastasis.

PMID- 7721019
TI  - Ischemic colitis complicating flexible endoscopy in a patient with connective
      tissue disease.

PMID- 7721020
TI  - An improved method of handling endoscopic biopsy specimens.

PMID- 7721021
TI  - Endoscopic injection for the treatment of bleeding ulcers: local tamponade or
      drug effect.

PMID- 7721022
TI  - Endoscopic treatment and restrictive surgical policy in the management of peptic
      ulcer bleeding: five years' experience in a central hospital.

PMID- 7721023
TI  - Non-steroidal anti-inflammatory drugs (NSAID) cause gastrointestinal ulcers
      mainly in Helicobacter pylori carriers.

PMID- 7721024
TI  - Effectiveness of current technology in the diagnosis and management of lower
      gastrointestinal hemorrhage.
AB  - Lower gastrointestinal hemorrhage is a common clinical problem for which multiple
      diagnostic tests and therapeutic interventions have been developed but no optimal
      approach has been established. We reviewed 107 consecutive patients admitted to
      the Massachusetts General Hospital for management of acute lower gastrointestinal
      hemorrhage to determine the effectiveness of diagnostic and management
      technologies, with particular attention to urgent colonoscopy. Colonoscopy
      yielded a diagnosis in 90% of patients, provided the opportunity for successful
      therapy in 9 of 13 patients (69%), and shortened hospital stay. Angiography
      performed after a scan positive for bleeding was often diagnostic, and
      angiography provided the means for successful therapy in 5 of 10 patients (50%).
      Barium enema and sigmoidoscopy had lower clinical yields. Although roles exist
      for other technologies, colonoscopy is the most convenient and effective first
      test in the evaluation of patients with significant lower gastrointestinal
      hemorrhage. Diagnostic yield, therapeutic opportunity, and cost effectiveness are
      maximized in early studies.

PMID- 7721025
TI  - Efficacy, safety, and cost of intravenous sedation versus general anesthesia in
      children undergoing endoscopic procedures.
AB  - We prospectively evaluated 226 patients under 18 years of age who underwent 296
      procedures, and intravenous sedation and general anesthesia were compared in
      regard to efficacy, safety, and cost. Children 6 to 9 years of age required the
      highest doses of midazolam (0.14 +/- 0.04 mg/kg) and meperidine (2.5 +/- 0.8
      mg/kg). A Relative Adequacy Scale, constructed to assess each patient's arousal
      and cooperation during intravenous sedation, revealed a 95% completion rate.
      Heart rate monitored before, during, and after the procedure was similar in both
      groups during the procedure, but a lower preprocedure heart rate was noted in
      older patients having intravenous sedation, suggesting less patient anxiety.
      Average charges, excluding endoscopist's and pathology fees, were $768.52 in the
      intravenous sedation group versus $1,965.42 in the general anesthesia group.
      Endoscopic procedures can be performed safely, effectively, and at a lower cost
      to the patient under intravenous sedation in a properly equipped and staffed
      pediatric endoscopy suite.

PMID- 7721026
TI  - Pharmacological and clinical implications of MAO-B inhibitors.
AB  - Although the involvement of monoamine oxidase B (MAO-B) in physiological function
      is not yet well understood, its inhibitors have been shown to be quite useful in
      the treatment of various neuropsychiatric disorders. Platelet MAO-B activity has
      been found to be reduced in several psychiatric disorders, related to substance
      abuse and associated with different personalities. 1-Deprenyl (selegiline), an
      archetypical MAO-B inhibitor, alone does not seem to exert an antidepressive
      effect, however, it may become useful when administered in combination with amine
      neurotransmitter precursors. MAO-B inhibitors are useful adjunct drugs to 1-DOPA
      in the symptomatic treatment of Parkinson's disease. Interestingly, 1-deprenyl
      alone can slow down the progress of otherwise disabled syndromes of Parkinson's
      disease. It has been proposed that 1-deprenyl may play a role in neuroprotection
      and neurorescue. MAO-B inhibitors can selectively and dramatically increase the
      level of beta-phenylethylamine, which has been shown to potentiate dopamine and
      noradrenaline function in the central nervous system. Several new types of highly
      selective, reversible and irreversible MAO-B inhibitors have recently been
      developed. The mechanism(s) of neuroprotective and rescue actions of 1-deprenyl
      and other MAO-B inhibitors will help to shed some light on our understanding of
      the neurodegenerative process.

PMID- 7721027
TI  - Nitric oxide release and long term potentiation at synapses in autonomic ganglia.
AB  - 1. Long-term potentiation (LTP) of synaptic transmission in autonomic ganglia is
      reviewed, together with the possible role of nitric oxide (NO) in this process.
      2. Calcium levels in preganglionic nerve terminals are elevated during at least
      the induction phase of LTP following a tetanus as well as during LTP induced by
      transmitter substances acting on the nerve terminals. Of the large number of
      calcium-dependent processes in the nerve terminal that might affect transmitter
      release, only calcium-calmodulin has been shown to be important in both the
      induction and maintenance of LTP. 3. The possibility that there is a decrease in
      the open time of nerve-terminal potassium channels following a tetanus, leading
      to an increase in duration of the terminal action potential and hence an increase
      in calcium influx and transmitter release is considered. There is little evidence
      for such an effect as yet for preganglionic nerve terminals. 4. Phosphorylation
      of potassium channels by cAMP-dependent protein kinase can lead to their
      inactivation with consequent action potential broadening in some systems.
      Exogenous cAMP enhances synaptic efficacy at preganglionic nerve terminals.
      Whether this occurs through an inactivation of potassium channels is not known.
      5. Nitric oxide (NO) synthase is present in both sympathetic ganglia and the
      ciliary ganglia. NO increases synaptic efficacy in both ganglia. In at least the
      case of ciliary ganglion this is due to elevation of quantal secretion. 6. NO can
      in some conditions increase the terminal action potential duration in ciliary
      ganglia, probably through decrease in the Ic potassium current. There is evidence
      that this happens through cGMP modulating cAMP phosphodiesterases, thereby
      affecting cAMP phosphorylation of the Ic channel. 7. Blocking NO synthase
      markedly decreases LTP following a tetanus in the ciliary ganglion. The
      possibility is considered that NO is released from the terminal during a tetanus
      and through altering cAMP phosphorylation of Ic enhances transmitter release.

PMID- 7721028
TI  - The role of cyclic nucleotides in the action of peripheral-type benzodiazepine
      receptor ligands in rat aorta.
AB  - 1. Peripheral-type benzodiazepine ligands (Ro 5-4864, AHN-086, PK 11195 and PK
      14105) inhibit, in a concentration-dependent and non-competitive manner,
      noradrenaline-induced contractions in isolated rat aortic rings (IC50 values: 24
      +/- 1.8, 49 +/- 2.5, 15 +/- 1.2, 49 +/- 3.2 microM, respectively). 2. This effect
      is probably not mediated by peripheral-type benzodiazepine receptors and is not
      related to the presence of endothelium. 3. All compounds inhibited
      phosphodiesterase activity in vitro. 4. From the results obtained with nucleotide
      analogs, calcium antagonists and specific inhibitors of PDE isoenzymes, it can be
      concluded that the actions of AHN-086 and PK 11195 are related to effects on PDE
      I, III and IV.

PMID- 7721029
TI  - Cephalexin concentrations in radicular granuloma following a single oral
      administration of 250- or 500-mg cephalexin.
AB  - 1. Cephalexin concentrations in radicular granuloma and serum following a single
      oral administration of 250- or 500-mg cephalexin were measured by a paper disk
      method. 2. The highest concentration of cephalexin in radicular granuloma
      following administration of 250-mg cephalexin to nonfasting patients was observed
      at 2 hr, and was 1.62 micrograms/g. The mean cephalexin concentration ratio of
      radicular granuloma/serum at 2 hr was 0.35. 3. The highest concentrations of
      cephalexin in radicular granuloma following administration of 500-mg cephalexin
      to nonfasting and fasting patients occurred at 2 and 1.5 hr, and was 3.35 and
      3.42 micrograms/g, respectively. Mean cephalexin concentration ratios of
      radicular granuloma/serum at 2 and 1.5 hr were 0.32 and 0.30, respectively. 4.
      All mean cephalexin concentrations in radicular granuloma following
      administration of 500-mg cephalexin to both fasting and nonfasting patients
      exceeded MIC for 90% (2 micrograms/ml) of clinically isolated strains of alpha
      hemolytic streptococci. However, those concentrations obtained by 250-mg
      cephalexin did not exceed it.

PMID- 7721030
TI  - Renal protective effect of efonidipine hydrochloride (NZ-105), a new calcium
      antagonist, in spontaneously hypertensive rats.
AB  - 1. We investigated the renal protective effect of efonidipine hydrochloride (NZ
      105) in spontaneously hypertensive rats (SHR). SHR were given a diet containing
      0.075% NZ-105 from 8 weeks old for 20 weeks. 2. 24-hr urinary protein excretion
      in the control SHR (drug-free diet) increased with age (from 77.3 mg/kg/day at 8
      weeks old to 385.4 mg/kg/day at 28 weeks old), while that in NZ-105-treated SHR
      was maintained at almost the same level as that in Wistar-Kyoto rats (WKY),
      matched control animals throughout the experimental period. 3. The histological
      changes of the kidney were examined by light microscopy at the end of the
      treatment period. In control SHR, swelling and hyalinization of glomeruli,
      dilatation of renal tubules containing hyaline casts and arteriolosclerosis were
      revealed. The long-term administration of NZ-105 markedly suppressed these
      changes. 4. The kidney weights and plasma creatinine concentration in control SHR
      were higher than those in WKY, while they were significantly reduced in NZ-105
      treated SHR. The long-term administration of NZ-105 also suppressed the elevation
      of systolic blood pressure and the increases of plasma renin activity and
      aldosterone concentration. 5. These findings suggest that NZ-105 inhibits the
      development of proteinuria and progressive kidney damage in SHR and may become a
      useful antihypertensive drug with the renal protective effect.

PMID- 7721031
TI  - Interaction of permanently charged metoclopramide analogs with D-2 dopamine
      receptors.
AB  - 1. The binding of permanently charged benzamides to the D-2 dopamine receptor of
      striatal membranes was compared with that of tertiary amine benzamides. 2. The
      permanently charged benzamides were able to inhibit the binding of [3H]-spiperone
      to striatal membranes but were less potent than the corresponding tertiary
      amines. 3. Removal of sodium or decreasing the pH from 7.8 to 6.2 decreased the
      binding of all benzamides tested, but the permanently charged analogs were
      affected less by these changes than the tertiary amines. 4. These results suggest
      that while the binding properties of the permanently charged benzamides are
      similar to those of the tertiary amine benzamides, there are differences in the
      manner in which these compounds interact with the D-2 receptor.

PMID- 7721032
TI  - Additive hypothermic effects of cocaine and nicardipine in guinea-pigs.
AB  - 1. This study investigated the thermoregulatory effects of cocaine combined with
      two reported antidotal treatments for acute cocaine overdosage, calcium channel
      blocker therapy and cold ambient temperatures. 2. Cocaine and nicardipine alone
      lowered the core temperature of female guinea-pigs (ambient temperature, 5
      degrees C) which resulted in a drop in core temperature of approximately 2
      degrees C at their highest respective doses (40 mg/kg and 50 mg/kg). 3.
      Nicardipine administration 30 min prior to cocaine caused an almost 2-fold drop
      in temperature (3.75 degrees C) relative to either drug alone. 4. The data
      suggest that cocaine and nicardipine produce hypothermia by different, but
      additive, mechanisms.

PMID- 7721033
TI  - Ouabain actions on the spontaneous activity and ionic currents in rabbit sino
      atrial node cells.
AB  - 1. The effects of ouabain on the action potentials and the membrane currents in
      spontaneously beating rabbit sino-atrial (SA) node cells were examined using the
      two-microelectrode technique. 2. Cumulative administrations of ouabain (10(-8) to
      10(-6) M) caused a negative chronotropic effect in a concentration-dependent
      manner. The effect was not modified by atropine (10(-7) M). At 10(-6) M, ouabain
      prolonged the duration of action potentials, but other parameters were unaffected
      to any significant extent. Ouabain elicited an arrhythmia, and increasing
      concentrations increased the incidence of arrhythmia (75% at 3 x 10(-7) M). 3.
      Pretreatment with clonidine (10(-6) M), a selective agonist of presynaptic alpha
      2-adrenoceptors, completely blocked the development of arrhythmia induced by
      ouabain (3 x 10(-7) M). Prazosin (10(-6) M), an alpha 1 antagonist, had similar
      effects, and yohimbine (10(-6) to 10(-5) M), an alpha 2 antagonist, did not
      affect the arrhythmias. 4. Ouabain (10(-8) to 10(-6) M) inhibited the slow inward
      and the time-dependent outward currents, but enhanced the hyperpolarization
      activated inward current, in a concentration-dependent manner. The time course of
      inactivation phase for Isi was composed of two (fast and slow) components.
      Ouabain decreased the fast component and increased the slow component. The
      voltage of half-maximum activation for the outward current was not affected.
      Ouabain elicited a transient inward current on the repolarizing step, and also on
      the depolarizing step.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721034
TI  - The role of 5-HT3 receptors in the anti-ulcer effect of calcitonin.
AB  - 1. The aim of the present study was to determine the role of 5-HT3 receptors of
      the gastroprotective effect of salmon calcitonin (sCT) and sCT-induced changes in
      gastric, hepatic, brain and brainstem glutathione (GSH) and lipid-peroxidation
      (LP) levels in rats subjected to cold-immobilization stress. 2. Stress exposure
      resulted in ulcer formation and a decrease in GSH levels of the liver, brain and
      brainstem and an increase in gastric and hepatic LP (P < 0.05). 3. sCT prevented
      stress-induced gastric ulcer development (P < 0.01) and reversed the decrease in
      hepatic and brain GSH levels (P < 0.05). 4. In the present study, a 5-HT3
      receptor antagonist, ICS 205,930 was used. Interestingly, the effect of the
      blocker on GSH and LP levels of the tissues studied was similar to those of sCT.
      5. ICS 205,930 dose dependently reversed the anti-ulcer effect of sCT although it
      did not antagonize the effect of sCT on GSH and LP levels, but it seemed to show
      an additive interaction for brain and brainstem GSH and gastric LP levels with
      sCT.

PMID- 7721035
TI  - Increased affinity of histamine H1 binding to membranes of human myometrium at
      the end of pregnancy.
AB  - 1. The characterization of H1 binding sites in membrane preparations of human
      myometrium obtained from pregnant and non-pregnant women was performed by using
      3H-mepyramine as the radioactive ligand. 2. Saturation curve analysis revealed
      that 3H-mepyramine is bound to a single class of binding sites. Changes in the H1
      site binding parameters were observed at the end of pregnancy, resulting in an
      increased affinity relative to non-pregnant tissue (Kd: 131.0 +/- 8.8 (non
      pregnant) and 72.5 +/- 7.5 (pregnant) nM, n = 6, P < 0.01). 3. A reduction in
      receptor concentration at the end of pregnancy was also observed, [Bmax: 565.2 +/
      43.7 (non-pregnant) and 309.6 +/- 25.9 (pregnant) fmol/mg prot, n = 6, P <
      0.01]. It is possible that this reduction in Bmax could be attributed to a
      dilution factor due to the increase in membraneous proteins that occurs during
      gestation.

PMID- 7721036
TI  - Actions of selected proteins, peptides and amino acid derivatives on mouse
      embryonic development in vitro.
AB  - 1. The actions of various compounds with antiproliferative and/or
      immunomodulatory activities including the ribosome-inactivating protein gelonin,
      the tetrapeptide tuftsin, the opioid peptide leucine-enkephalin, the
      antireproductive tripeptide Thr-Ser-Lys, the melatonin analog 6-methoxy-2
      benzoxazolinone, and the amino acid derivatives 5-hydroxytryptamine and oxalysine
      on mouse embryonic development and organogenesis in vitro were investigated. 2.
      The various compounds were tested up to a concentration of 300 micrograms/ml. It
      was found that only 6-methoxy-2-benzoxazolinone, a derivative of tryptophan,
      produced an increase in the number of abnormal embryos and reductions in the
      final somite numbers and axial lengths of embryos. 3. 6-Methoxy-2-benzoxazolinone
      treatment also resulted in an increased incidence of abnormal morphogenesis of
      various organ primordia, including abnormal yolk sac circulation, twisting of
      body axis, absence of forelimb bud and opening of cranial neural tube.

PMID- 7721037
TI  - Investigation of the fibrinolytic activity of defibrotide fractions.
AB  - 1. Defibrotide is a drug which is a mixture of DNA fragments of various lengths.
      To characterize the active component which is responsible for the fibrinolytic
      effect, we fractionated defibrotide by column chromatography and investigated
      direct and endothelium dependent fibrinolytic activity of the major fractions by
      euglobulin lysis time (ELT) measurements. 2. Defibrotide and its fractions added
      to human plasma samples did not change ELT. However addition of conditioned media
      of human umbilical vein endothelial cell cultures which were incubated with
      defibrotide or its high molecular weight fractions shortened the ELT
      significantly (P < 0.001), whereas small molecular weight fractions did not
      effect the ELT. 3. Our results show that high molecular weight defibrotide
      fractions have fibrinolytic activity and the effect is endothelium dependent.

PMID- 7721038
TI  - Cytotoxicity and accumulation of Hg, Ag, Cd, Cu, Pb and Zn in human peripheral T
      and B lymphocytes and monocytes in vitro.
AB  - 1. The cytotoxic effects of various heavy metals were assayed by trypan blue
      exclusion in vitro in human peripheral immune cells separated to high purity. T
      and B lymphocytes and monocytes were equally sensitive to metals. The individual
      metals could be ranked in the following decreasing order of cytotoxic potency, Hg
      approximately Ag > Cd approximately Cu > Pb approximately Zn, based on exposure
      time and concentration needed to give a particular percentage of dead cells. 2.
      The cytotoxic effects became irreversible after about 13 hr of metal exposure. 3.
      Examination by scanning electron microscopy showed that the heavy metals caused
      serious destruction of the cell membranes. 4. Solubility and uptake of metals
      into the cells were studied and discussed in relation to the cytotoxic effects.
      It was concluded that metal binding to cell surfaces or precipitate formation
      could inhibit ordinary uptake, thereby affecting cytotoxicity. For Pb in
      monocytes this appeared to lead to uptake of non-toxic complexes, probably by
      phagocytosis.

PMID- 7721039
TI  - The effect of lithium on morphine-induced analgesia in mice.
AB  - 1. The effects of acute and chronic lithium (Li+) treatments on the
      antinociception caused by morphine were studied in mice using the tail-flick
      test. 2. Subcutaneous injection of morphine (10 mg/kg) caused significant
      antinociception. 3. Acute Li+ administration (0.05, 0.1, 0.3, 1, 5 and 10 mg/kg,
      i.p.) alone had no significant antinociceptive effect but changed morphine
      analgesia; low doses of Li+ (0.1, 0.3 and 1 mg/kg) were found to decrease the
      antinociception induced by morphine whereas higher doses of the drug (10 mg/kg)
      potentiated this effect. 4. The 6 day administration of Li+ with a serum level of
      0.528 mM decreased the antinociceptive effect of morphine. 5. The effect of Li+
      on morphine-induced analgesia persisted for 96 hr in spite of the fact that Li+
      drinking was discontinued (the serum Li+ level decreased from 0.528 to 0.022 mM).
      6. It has been reported that Li+ might change both the binding of opioids to
      their receptors and biosynthesis or release of endogenous opioids. There is also
      a considerable body of evidence which indicates that both Li+ and morphine affect
      phosphoinositide turnover, intracellular calcium content and cyclic AMP level.
      The interaction of two drugs may conceivably take place through these systems. 7.
      These data suggest that the biological effects of Li+ may exist at very much
      lower serum Li+ levels than the commonly accepted therapeutic range.

PMID- 7721040
TI  - Pre- and postjunctional muscarinic receptor subtypes in the vas deferens of rat.
AB  - 1. A pharmacological study of the pre- and postjunctional muscarinic receptors of
      the isolated rat vas deferens was carried out using more selective agonists and
      antagonists. 2. The prejunctional receptor was characterized on electrically
      stimulated preparations, while the postjunctional receptor was studied on vasa
      deferentia without stimulation. 3. The results indicate that atropine exhibited a
      similar affinity for the two populations of muscarinic receptor subtypes of this
      tissue. 4. 4-DAMP was able to differentiate with high affinity a subtype located
      at postjunctional level which had pharmacological similarities with the M3-ACh
      subtype and with low affinity a subtype located at prejunctional level. 5. The
      selective M1-ACh agonist McN-A-343 was not able to activate the postjunctional
      receptor, but showed a similar affinity to ACh for the prejunctional one. 6. At
      present, the prejunctional receptor can be considered as an atypical M1-ACh
      subtype based on the results obtained with the selective drugs available.

PMID- 7721041
TI  - Positive inotropic activity of the novel histamine H2-receptor agonist,
      amthamine, on the human heart in vitro.
AB  - 1. We tested the novel thiazole derivative, amthamine, for its ability to
      stimulate histamine H2-receptors in the human myocardium. 2. Experiments were
      carried out on isolated, electrically-driven pectinate muscle segments, excised
      from atrial appendages of patients undergoing corrective heart surgery. 3.
      Amthamine (0.3-100 microM) induced a positive inotropic activity, resembling
      histamine in terms of potency and efficacy. In comparison, impromidine was 10-30
      times more active than histamine and amthamine, but its maximum effect was
      significantly lower, while dimaprit was as effective as histamine, but 10 times
      less potent. 4. The selective histamine H2-blocker, famotidine antagonized in a
      competitive fashion the amthamine-induced positive inotropic effect. pA2 value of
      famotidine against amthamine (7.21 +/- 0.45) was close to that measured against
      histamine (6.88 +/- 0.31) in the same conditions. 5. The effect of amthamine was
      not modified by beta-adrenoceptor blockade, excluding direct or indirect
      sympathomimetic activities of the compound. 6. These data provide evidence that
      amthamine is a selective and full acting histamine H2-receptor agonist in the
      human heart in vitro.

PMID- 7721042
TI  - Comparison of various calcium channel blockers on guinea-pig isolated common bile
      duct.
AB  - 1. The inhibitory effects of various calcium channel blockers; nifedipine,
      verapamil, diltiazem and a heterogenous compound, dantrolene, have been
      investigated on isolated common bile duct from guinea-pig. 2. All the compounds
      tested induced a concentration-dependent reduction of the amplitude of
      contractile response to electrical stimulation or increasing the calcium
      concentration of the bathing media. 3. Nifedipine was the most potent compound
      whereas the least potent was dantrolene; verapamil and diltiazem had intermediate
      potency. 4. The IC50 values for these compounds were calculated as: nifedipine
      3.68 x 10(-9) M; verapamil, 4.93 x 10(-8) M; diltiazem, 4.2 x 10(-7) M; and
      dantrolene 5.51 x 10(-5) M. 5. All the compounds displaced the concentration
      response curve of calcium chloride to the right in a concentration-dependent
      manner. Among the compounds studied, nifedipine had the highest and dantrolene
      had the lowest potency. 6. These results indicate the striking pharmacological
      effects of the calcium channel blockers on the common bile duct and may indicate
      a possible role for these compounds in the treatment of biliary colic.

PMID- 7721043
TI  - Effects of veratridine on Na and Ca currents in frog skeletal muscle.
AB  - 1. Voltage-clamp experiments were performed to determine the effects of
      veratridine on Na and Ca currents in frog skeletal muscle fibres. 2. Veratridine
      (1 microM) did not affect the kinetics of the fast Na current but it did induce a
      slowly inactivating tetrodotoxin-sensitive inward current that was apparent after
      Na current inactivation. This slow current had a peak amplitude of 6.7 +/- 0.7
      microA/cm2 at -20 mV and decayed monoexponentially with a time constant of 606 +/
      77 ms. 3. The slow current had a voltage-dependence for activation that was
      similar to that of the fast Na current. Single depolarizing prepulses that
      induced complete inactivation of the fast Na channels, prevented development of
      the slow current. Trains of brief depolarizations at increasing frequencies
      increased the amplitude of the slow current. These results suggest that the slow
      current may be mediated by veratridine modified Na channels that must be in the
      open position. 4. The low concentration of veratridine (1 microM) did not affect
      the Ca current, while 100 microM veratridine reversibly suppressed the Ca current
      and shifted its peak current-voltage relation towards more negative potentials.
      Thus, veratridine appears not to be a selective fast Na channel modifier as it
      may also alter Ca channel gating properties in skeletal muscle fibres.

PMID- 7721044
TI  - Effects of veratrine on ion currents in single rabbit cardiomyocytes.
AB  - 1. Voltage-clamp experiments were performed to determine the effects of veratrine
      (1 microgram/ml) on Na and K currents in isolated rabbit ventricular
      cardiomyocytes. 2. Veratrine did not affect the inward rectifier K current,
      increased the inactivation time constant of the transient outward current (I(to))
      and induced a slowly decaying inward current component (Iv), which was sensitive
      to tetrodotoxin. 3. Inactivation of fast Na channels by application of short
      depolarizing prepulses to potentials between -90 and -50 mV prevented the
      development of Iv.Iv decayed biexponentially with time constants equal to 139 +/-
      9.0 ms and 776 +/- 47 ms. The net amplitude of Iv and the time constants for its
      rapidly and slowly inactivating components were little affected by trains of
      conditioning prepulses to 0 mV. The contributions, however, of the fast and slow
      components to the net current were significantly altered by repetitive
      depolarizations. 4. These components of Iv are likely due to modification of open
      cardiac Na channels by veratrum alkaloids.

PMID- 7721045
TI  - Effects of tyrosine kinase inhibitor, genistein, and phosphotyrosine-phosphatase
      inhibitor, orthovanadate, on Ca(2+)-free contraction of uterine smooth muscle of
      the rat.
AB  - 1. The effects of a protein-tyrosine kinase inhibitor, genistein, and a protein
      tyrosine phosphatase inhibitor, orthovanadate, were tested on the Ca(2+)-free
      contraction of the estrogen-dominated rat, which has been proved to be induced
      mainly via protein kinase C entirely independently of Ca2+. 2. Genistein (30
      microM) significantly inhibited the contraction indicating participation of
      tyrosine kinase activity in the contraction. 3. Orthovanadate caused contraction
      concentration-dependently and augmented the Ca(2+)-free contraction at
      concentrations of more than 1 microM. The contraction by orthovanadate was not
      inhibited so significantly by genistein (30 microM). 4. Possible participation of
      tyrosine kinase activity in Ca(2+)-free contraction is discussed in addition to
      the formerly reported participation of protein kinase C.

PMID- 7721046
TI  - Vasoconstrictor-mediated release of purines and pyrimidines from perfused rat
      hindlimb, perfused mesenteric arcade and incubated de-endothelialized aorta.
AB  - 1. Reperfusion of hindlimbs that had previously been exposed to either 10 or 60
      min global ischaemia resulted in transient washouts of uracil and uric acid in
      approximate proportion to the interval of ischaemia. However, changing the
      interval of sequential angiotensin II infusions from 10 to 60 min did not affect
      the magnitude of sustained uracil and uric acid release. 2. Perfused rat
      mesenteric artery arcade released uracil and uric acid and each was further
      increased approximately 2-fold by exposure to the vasoconstrictor, serotonin (6.7
      microM). 3. Incubated de-endothelialized rat aorta also released purines and
      pyrimidines and this was increased further when subjected to increased work
      loads. 4. The increased rates of release of purines and pyrimidines from
      hindlimb, and the simpler vascular preparations of mesenteric arcade and aorta,
      were in proportion to the relative rates of increase in oxygen consumption under
      maximum vascular load. 5. It is concluded that the release of purine and
      pyrimidine nucleosides and their catabolites from perfused rat hindlimb occurring
      as a consequence of vasoconstriction is not the result of release from previously
      ischaemic tissue. In addition, release of purines and pyrimidines appears to be a
      general feature of vascular smooth muscle subjected to high workloads.

PMID- 7721047
TI  - Angiotensin modulation of vascular tone and adrenergic neurotransmission in cat
      femoral arteries.
AB  - 1. AI and AII induced contractions in cat femoral arteries, which were inhibited
      by saralasin. 2. The response to AI was reduced by captopril and endothelium
      removal and by chymostatin in endothelium-denuded segments. 3. AII contractions
      were increased by indomethacin, L-NAME and endothelium removal. 4. AII and AI
      facilitated the adrenergic neurotransmission. This facilitation was inhibited by
      saralasin and/or captopril. 5. These data suggest: (1) AI is converted into AII
      in the endothelial and adventitial layer; (2) the contractions caused by AI and
      AII are mediated by AII receptors and are modulated by endothelial release of NO
      and PGI2; and (3) the existence of presynaptic AII receptors mediating the
      facilitation of neurotransmission caused by AI and AII.

PMID- 7721048
TI  - Benzpyrene treatment in adulthood increases the testosterone level in neonatally
      steroid(allylestrenol)-treated male rats.
AB  - 1. Serum testosterone level was significantly elevated in adult male rats after a
      single perinatal allylestrenol administration. 2. Benzpyrene treatment of adult
      rats perinatally treated with allylestrenol, did not cause changes 1 week after
      benzpyrene treatment, but 3 weeks later an extremely high serum testosterone
      level was found. 3. In control animals benzpyrene administration in adulthood did
      not influence the serum testosterone level either 1 or 3 weeks following the
      treatment.

PMID- 7721049
TI  - Alpha-adrenergic receptor-mediated thermogenesis in brown adipose tissue of rat.
AB  - 1. The present studies were undertaken to characterize the thermogenic response
      to the alpha 1-adrenergic agonist phenylephrine, to compare this response with
      the beta-adrenergic response and to assess the role of brown adipose tissue
      (BAT). 2. Phenylephrine and the beta 3-adrenergic agonist CGP 12177A each caused
      similar increases in O2 consumption. No synergism was observed when combining the
      two drugs. Phenylephrine stimulated O2 consumption via an alpha-adrenergic
      mechanism, as indicated by effective blockade with phenoxybenzamine, but not
      propranolol. 3. Further evidence for the alpha-adrenergic mechanism of
      phenylephrine action was seen in studies with BAT membranes. Phenylephrine did
      not stimulate adenylyl cyclase and did not potentiate beta-adrenergic stimulation
      of adenylyl cyclase. 4. Skeletal muscle was not a major site of phenylephrine
      stimulated O2 consumption, as the response was not inhibited by a concentration
      of dantrolene which inhibited cold-induced muscle shivering. 5. Phenylephrine
      caused an increase in the density of available 3H-GDP binding sites in BAT
      mitochondria, indicating an activation of BAT thermogenesis in vivo. This
      increase was equal in magnitude to what we have reported previously for CGP
      12177A. No changes were observed in the affinity for 3H-GDP. 6. We concluded that
      phenylephrine stimulates O2 consumption by an alpha-adrenergic mechanism that
      involves activation of BAT thermogenesis. It remains to be determined whether the
      activation of BAT occurs by a direct or indirect mechanism.

PMID- 7721050
TI  - A comparison of the relaxant effects of pinacidil in rabbit renal and mesenteric
      artery.
AB  - 1. The relaxant effects of pinacidil were compared in isolated rabbit renal and
      mesenteric artery. 2. Pinacidil (10 nm-300 microM) relaxed renal and mesenteric
      arterial rings precontracted with phenylephrine with pD2 values of 5.11 +/- 0.03
      and 6.27 +/- 0.04, respectively. 3. The inhibitory effect of pinacidil on the
      rabbit mesenteric artery was competitively antagonized by glibenclamide (1-10
      microM). The calculated pKB value was 6.37 +/- 0.04. On the renal artery,
      glibenclamide (2-20 microM) did not significantly affect pinacidil-induced
      relaxation (P > 0.05). 4. Tetraethylammonium (TEA, 1-10 mM) competitively
      antagonized the pincaidil induced relaxation of the rabbit renal artery. The pKB
      value was 3.22 +/- 0.08. On the mesenteric artery TEA antagonized the effect of
      pinacidil in a noncompetitive manner. 5. The concentration-response curves for
      pinacidil on the rabbit renal and mesenteric artery were not affected by apamin
      (0.1 microM). 6. It is concluded that ATP-sensitive K+ channels (KATP) are not
      involved in pinacidil action on the rabbit renal artery. On the contrary, KATP
      are probably major sites of pinacidil action on the rabbit mesenteric artery.

PMID- 7721051
TI  - Effects of gentamicin on rat submandibulary gland functions.
AB  - 1. Submandibular saliva was collected from anesthetized gentamicin-treated and
      control rats using carbachol, isoproterenol and pilocarpine as secretagogue. 2.
      Intraperitoneal injection of a large single dose (80 mg/kg) of gentamicin caused
      marked changes in saliva flow rate, protein and electrolyte concentrations in the
      presence of parasympathetic or sympathetic agents used as stimulants. 3. The
      secretion of N-acetyl-beta-D-glucosaminidase in saliva was determined and there
      was a marked increase in the enzyme activity of saliva of gentamicin-treated rats
      in comparison to that of controls. 4. The results of this study suggest that
      gentamicin as an aminoglycoside antibiotic at the dose employed, can influence
      the secretory mechanisms of rat submandibular glands.

PMID- 7721052
TI  - Effect of histamine on soluble and membrane-associated carbonic anhydrase (CA)
      activity of pig and bovine gastric mucosa.
AB  - 1. As part of their characterization, the effect of histamine (H) on both soluble
      and membrane-associated carbonic anhydrase (CA) activity of pig and bovine
      gastric light microsomal membranes was investigated. 2. H did not affect the
      activity of soluble CA purified from pig oxyntic mucosa, whereas 10(-7) and 10(
      4) M H produced a significant enhancement of pig gastric firmly-membrane
      associated CA activity at 20 and 30 degrees C (about 2-3-fold), but it failed at
      0 degree C. The increase of activity produced by H occurred within 1 min and it
      was maintained for at least 15 min. 3. H also stimulated bovine gastric firmly
      membrane-associated CA activity, the stimulation also being dependent on
      temperature.

PMID- 7721053
TI  - The pharmacological effects of cadmium on skeletal neuromuscular transmission.
AB  - 1. Cadmium (100 microM) blocks neuromuscular transmission by blocking
      prejunctional voltage dependent calcium channels in a competitive manner. 2.
      Prolonged exposure to cadmium leads to a block of neuromuscular transmission that
      is not competitive. 3. Cadmium can increase the spontaneous release of
      acetylcholine, this release is modified by the cation composition of the bathing
      solution. 4. Cadmium may enter the nerve terminal via the voltage dependent
      calcium channels (the L-type calcium channel has been implicated) and exert some
      of its actions intracellularly. 5. All of the extracellular effects of cadmium
      can be reversed by cysteine.

PMID- 7721054
TI  - Addictive behaviors: relationship factors and their perceived influence on
      change.
AB  - An empirical study of a British clinical population is reported, in which the
      influence of relationships on confidence in maintaining change across a number of
      addictive behaviors was investigated. The hypothesis was that the perceived
      quality of relationships would be correlated with a client's confidence in
      sustaining abstinence or change. It was also thought that qualitative data would
      help clarify some of the underlying processes mediating such a link if it were
      established. The results largely supported the predictions, although relationship
      difficulties were significantly more common in gamblers and alcoholics compared
      with smokers and overeaters. The discussion develops the view that the notion of
      emotional disclosure and system theory's emphasis on circular causality are
      particularly useful concepts in making sense of the data.

PMID- 7721055
TI  - Stress and organizational role conflict.
AB  - In this study the research on role conflict and coping is integrated with more
      traditional lines of stress research. It is argued that, because role stress is
      generated by certain characteristics of a person's environment, coping with role
      stress is likely to be directed toward those environmental characteristics. The
      literatures on stress, role conflict, and coping are reviewed. The following
      conclusions are theorized: (a) The relation between role conflict and role stress
      is moderated by the strain existing within a person's social network; (b) this
      strain is produced by two factors, the perceived power of the role sender and the
      importance of the sender's expectations to the focal person; (c) the relation
      between role stress and role distress (felt emotional discomfort) is moderated by
      several personality characteristics; (d) the relation between role distress and
      coping (actual behavior aimed at reducing distress) is moderated by both
      individual-level and situational-level factors; (e) the relation between coping
      and strain can be reciprocal. The need for longitudinal, reciprocal studies of
      stress, distress, and coping, and for occupationally, and even organizationally,
      specific models of stress, is also emphasized (Bacharach & Bamberger, 1992).

PMID- 7721057
TI  - [Cloning and expression of a plasmid pBS195 gene, determining oxygenase activity,
      in Escherichia coli cells].
AB  - Plasmid pBS195, detected in a strain of Lactobacillus sp. isolated from long
      living persons, has a broad host range, including Gram-positive and Gram-negative
      microorganisms [1]. Plasmid-harboring colonies of the strain Escherichia coli
      HB101 give a color reaction with catechol. This indicates that genes mediating
      the activity of oxygenase are present in this plasmid. The high activity level of
      this enzyme, mediated by pBS195, and substrate specificity, which has not bee
      detected in any known metapyrocatechases, were found in cells of E. coli.
      Hybridization with a 32P-labeled fragment containing the NahC gene revealed a
      region of homology with a 1.6-kb EcoR I- BamH I fragment of plasmid pBS195.
      Deletion variants of this plasmid that lost oxygenase activity confirmed the
      location of the oxygenase gene in this region. The gene responsible for oxygenase
      activity in the plasmid was cloned on the pUC19 vector in E. coli cells. The
      expression of the cloned gene is controlled by the lac promoter of this vector.
      Physical, hybridization, and deletion analyses as well as analysis of
      polypeptides, which are synthesized in E. coli mini-cells, showed that this
      activity requires the participation of a polypeptide with molecular mass of 34
      kDa.

PMID- 7721056
TI  - [A new open reading frame in the genome of cyanobacteria Synechocystis sp. PCC
      6803].
AB  - A new open reading frame ORF242, coding for a 26.47-kDa polypeptide, was found in
      a DNA fragment of the cyanobacterium Synechocystis 6803, transforming a
      photosynthetic mutant to photoautotrophy and having homology with plant
      chloroplast DNA. In the 5' flanking region of ORF242, consensus sequences
      characteristic of a functioning gene were found. One copy of ORF242 is present in
      the Synechocystis 6803 genome. Insertion inactivation of ORF242 does not lead to
      a decrease in photosynthetic activity in cells of cyanobacteria but may influence
      the ratio between active complexes of photosystems I and II.

PMID- 7721058
TI  - [Strategies for selection and stability to asphyxia in larvae of the malaria
      mosquito Anopheles messeae with various karyotypes].
AB  - Sensitivity to asphyxia (oxygen deficiency) Anopheles messeae larvae was studied.
      It was demonstrated that mosquitoes with mosquitoes with "northern" chromosome
      inversions perish underwater more more quickly than mosquitoes with "southern"
      karyotypes. Apparently, resistance to asphyxia is a component of the adaptive
      strategy and is maintained by K-selection. The respiration and energy metabolism
      of larvae with different gene complexes are discussed.

PMID- 7721059
TI  - [Nucleolus organizer regions and B-chromosomes of field mice (Mammalia, Rodentia,
      Apodemus)].
AB  - Distribution of nucleolus organizer regions (NORs) in karyotypes was studied in
      10 species of wood mice, including Apodemus flavicollis, A. sylvaticus, A.
      uralensis (= A. microps), A. fulvipectus (= A. falzfeini), A. ponticus, A.
      hyrcanicus, A. mystacinus, A. agrarius, A. peninsulae, and A. speciosus.
      Peculiarities of NOR location in karyotypes can be used in interspecific
      diagnostics of wood mice. Intraspecific polymorphism of A. sylvaticus, A.
      agrarius, and A. peninsulae in terms of the number of NORs and their localization
      in chromosomes can serve as evidence for karyological differentiation in certain
      populations of these species. The minimum number of active NORs in mice of the
      genus Apodemus is two to four. Two A. flavicollis wood mice with karyotypes
      containing one small acrocentric B-chromosome (2n = 49) were identified among
      animals captured in Estonia. In A. peninsulae, B-chromosomes were found among
      animals captured in the following regions: the vicinity of Kyzyl (one mouse with
      17 microchromosomes, 2n = 65); the vicinity of Birakan (two mice with one
      metacentric chromosome each, 2n = 49); and in the Ussuri Nature Reserve (one
      mouse with five B-chromosomes, including three metacentric and two dotlike
      chromosomes; 2n = 65). In the latter animal, the presence of NORs on two
      metacentric B-chromosomes was revealed; this is the first case of identification
      of active NORs on extra chromosomes of mammals.

PMID- 7721060
TI  - [Genetic analysis of differences in metabolism of juvenile hormone in lines of
      Drosophila virilis resistant and sensitive to heat stress].
AB  - The metabolism of juvenile hormone (JH) in imagos of two Drosophila species (D.
      virilis and D. melanogaster) was studied in the normal state and after short-term
      heat stress. Females of both species respond to stress by a decrease in the
      activity of JH esterase. This decrease is realized through a decrease in the
      amount of protein. JH metabolism in males does not change after heat stress.
      Genetic analysis of differences in the activity of DPF-resistant JH esterase in
      stress-sensitive and stress-resistant strains of D. virilis was performed. The
      differences are controlled by one autosomal gene.

PMID- 7721061
TI  - [Polymorphism of natural Drosophila melanogaster populations by level of juvenile
      hormone metabolism and reaction to heat stress].
AB  - The juvenile hormone metabolism in Drosophila melanogaster females from the
      laboratory line Canton S and from two natural populations of the Altaiskii krai
      was studied under normal conditions and under heat shock. The Canton S females
      were shown to have a high level of juvenile hormone and responded to heat shock
      by decreasing it. The natural populations were polymorphic for this trait. In
      both populations examined, flies with a low level of the hormone occurred at high
      frequencies (56 and 64%). The natural populations were also polymorphic for
      response of the system of juvenile hormone metabolism to heat shock: flies with a
      low level of the hormone did not respond to stress by decreasing it.

PMID- 7721062
TI  - [Maternal effect of the mutagen-sensitive mutation mus(2)201G1 on mutagenesis in
      Drosophila melanogaster spermatozoid genome, induced by ethylene imine and
      methylmethane sulfonate].
AB  - The frequency of recessive sex-linked lethal mutations (RSLLM) induced in
      chromosome Muller-5 of mature sperms by treatment with ethyleneimine (EI) or
      methyl methanesulfonate (MMS) was shown to increase when male pronucleus or
      zygote was formed in the oocyte cytoplasm of the mutagen-sensitive line
      mus(2)201G1. The increase in the total number of mutations in the mutant
      cytoplasm was accompanied by a transformation of damages causing mosaic mutations
      into damage to the genome, which are recorded as complete mutations.

PMID- 7721063
TI  - [MR-chromosomes in Eurasian populations of Drosophila melanogaster].
AB  - In natural populations of Drosophila melanogaster, two mutator systems, MR and P
      M, are distributed throughout the world. Some evidence shows that these systems
      can be considered as one. Natural populations of D. melanogaster from Eurasia and
      North America are fundamentally different with regard to the P-M system.
      Comparison of Eurasian and North American populations with regard to the MR
      system was hindered by a lack of data concerning distribution and frequency of MR
      factors in Eurasia. In this paper, data on the MR-active chromosomes in natural
      populations of D. melanogaster from Russia and neighboring countries from 1977 to
      1992 are presented. The frequencies of MR chromosomes in Eurasian populations
      were shown to be similar to those in North America. Hence, on a global scale, the
      MR and P-M mutator systems are expressed independently.

PMID- 7721064
TI  - [Genetic variability of the sable (Martes zibellinna L.) by blood protein genes].
AB  - Electrophoresis of blood proteins was used to determine, for the first time, the
      level of genetic variability of certain loci in the sable (Martes zibellina L.,).
      Variation of 23 blood proteins encoded by 25 genes was analyzed. Polymorphism was
      revealed in six genes. The level of heterozygosity was estimated at 0.069; the
      proportion of polymorphic loci was 24%. Data on the history of the sable
      population maintained at the farm, on geographical distribution of natural sable
      populations, and on the number of animals selected for reproduction in captivity
      is presented. The great number of animals studied and the extensive range of
      natural sable populations, on the basis of which the population maintained in
      captivity was obtained, suggest that the results of this work can be used for
      estimating the variability of the gene pool of sable as a species.

PMID- 7721065
TI  - [Propagation of congenital anomalies of sexual development in the newborn
      population of Moscow].
AB  - The prevalence of congenital abnormalities of the genitals was estimated in
      newborns of the Moscow population in 1992 and 1993. The prevalence was found to
      be one case per 1500-1550 newborns. The pattern and structure of the observed
      pathology were studied. The range of patients who were not detected during the
      study, due to clinical peculiarities of their pathology, was estimated.

PMID- 7721066
TI  - [Genetic structure of the residents of Central Moldova].
AB  - Distributions of the marker genes for (1) blood groups ABO, Rhesus, MN, P, and
      Lewis; (2) some allotypes of G1m immunoglobulin; and (3) serum proteins Hp, Tf,
      and Gc; and (4) erythrocytic isoenzymes Acp and EsD were studied in 10 rural
      populations of central Moldova. For each local population, an empirical
      distribution of genotypes was obtained; and on this basis, allele frequencies,
      expected distributions of genotypes, and observed and expected heterozygosity
      were estimated. Significant differences between the studied populations with
      respect to variations of allele frequencies were found for the following loci:
      Hp, AcP, Gc, P, G1m, and Lewis. The results were compared with data on some
      populations of Western Europe and the CIS. Close relationships between indigenous
      Moldovans and other Romanic peoples, as well as the Russians and the Ukrainians,
      were demonstrated.

PMID- 7721067
TI  - [A multiexon deletion in the human low density lipoprotein receptor gene as a
      reason for familial hypercholesterolemia].
AB  - Inheritance of Taq I, BstE II, and Nco I restriction fragment length
      polymorphisms (RFLP) in three families from St. Petersburg with familial
      hypercholesterolemia (FH) was studied. In two of these families, polymorphic
      markers of the low density lipoprotein receptor (LDLR) gene cosegregated with the
      disease. This data confirmed FH diagnosis based on the analysis of blood plasma
      lipid levels. Three different RFLP haplotypes were associated with the disease,
      suggesting the presence of at least three point mutations in the LDLR gene in the
      population studied, i.e., suggesting molecular heterogeneity of FH in the St.
      Petersburg population.

PMID- 7721068
TI  - [Population risk of bronchial asthma occurrence in Moscow].
AB  - Age-specific prevalence and incidence of bronchial asthma (BA) were estimated in
      a number of districts in Moscow. The average prevalence was measured as the
      current proportion of BA patients registered in district outpatient clinics of
      both the center and periphery of Moscow (2442 patients in total) among the entire
      population served by to these clinics. This proportion was found to be 0.5% for
      both men and women. Before 25 years of age, BA appeared to be commoner in males
      (0.57%, versus 0.3% in females); after 40 years of age, it was commoner in
      females (0.89%, versus 0.47% in males). The morbidity of the disease measured as
      the frequency of new cases of BA (diagnosed for the first time in the given
      patient) had two maximums for each gender: in females, between birth and nine
      years of age and at 45-54 years (0.39 and 0.45%, respectively) and in males,
      between birth and nine years and at 55-64 years (0.75 and 0.74%, respectively);
      and a minimum at 20-29 years of age (0.14 and 0.05% for females and males,
      respectively). The majority (80%) of adult BA patients were first diagnosed with
      BA in adulthood. The dynamics of BA incidence appeared to differ in males and
      females. The male incidence changed more drastically with age, while the
      incidence in adult females reached a maximum 10 years earlier than in adult
      males. The population risk of being registered for BA (accumulated morbidity) by
      the age of 15, 40, and 80 was 0.98, 1.35, and 2.97%, respectively, for males and
      0.58, 0.95, and 2.13%, respectively, for females.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7721069
TI  - [Interaction between mutagenic activity and chemical structure in a series of
      biphenyl derivatives].
AB  - A comparative study of the mutagenic activity of 21 derivatives of biphenyl was
      performed in the strain TA1538 of Salmonella typhimurium. The position effect of
      carboxyl, amide, aldehyde, and ether groups was examined. The para position of
      substituents, among which at least one is a nitro group, causes mutagenic
      activity in most of the molecules studied. Derivatives of biphenyl that have no
      substituents in the para position were inactive. In addition, 4-nitrobiphenyl (4
      NBP), 4-nitro-2'-carboxy biphenyl (4-N-2'-C-BP), 4,4'-dinitro-2'-carboxy biphenyl
      (4-4'-DN-2'-C-BP), and 4,4'-dinitro-2,2'-carboxy biphenyl (4-4'-DN-2,2'-DC-BP)
      induced no frameshift mutations in TA1538. The most active was 2,4,4'-TN-6-C-6'
      Ad-BP, giving up to 800 revertants per nmol; 2,4,6,2'-TN-4'-6'-DC-BP and
      2,4,2',4'-TN-2'-C-BP, which induced 250 and 350 revertants per nmol,
      respectively, were highly active frameshift mutagens.

PMID- 7721070
TI  - [Determination of the direction of transcription of Escherichia coli K-12
      structural genes of the fructose regulon in vivo].
AB  - The direction of transcription of specific components of the fructose
      phosphotransferase system, the fruA, fruK, and fruB genes, was determined in vivo
      by plasmid F'ts1141ac. Transcription from each of these genes was shown to run in
      the same direction, counterclockwise with respect to the E. coli chromosomal map.

PMID- 7721071
TI  - [Spatial organization of chromosomes in oocytes and spermatocytes in malaria
      mosquitos].
AB  - It is shown that prophase chromosomes of oocytes in Anopheles messeae ovaries do
      not form local chromocenters, unlike spermatocytes, in which chromosomes fuse in
      a joint centromeric assembly. This fact reflects the dynamic nature of the system
      of chromocenter formation in generative tissues. During analysis of interspecific
      hybrids F1 A. maculipennis x A. subalpinus, no conjugation of homeologous
      chromosomes was observed, and the latter remained separated from one another.

PMID- 7721072
TI  - [The RAD58(XRS4) gene--mapping to the right shoulder of chromosome XIII].

PMID- 7721073
TI  - Variables in allergy skin testing.
AB  - Allergy skin testing for immediate hypersensitivity is affected by a number of
      factors, some under the control of and others not controllable by the operator.
      Uncontrollable factors include the patient's age, chronobiological variation, and
      variation in reactivity between different parts of the body. Controllable factors
      include medications the patient is using, the quality of the allergy extract
      employed, the distance between test sites, the choice of prick or intradermal
      technique, and in the case of percutaneous testing, the device that is used.
      Considering the importance of the information that is generated by skin testing,
      and the major therapeutic commitments often resulting, more attention should be
      given to the techniques employed. It is suggested that operator performance can
      and should be assessed by relatively simple tests.

PMID- 7721074
TI  - Practical approaches to the treatment of atopic dermatitis.
AB  - Atopic dermatitis is a chronic pruritic cutaneous disease that occurs in 0.5% to
      1% of the general population and affects almost 10% of all children. Since this
      is a disease that is associated with both a very high level of total IgE and a
      high incidence of allergic respiratory disease, it behooves the practicing
      allergist to become familiar with the diagnosis and treatment of atopic
      dermatitis. This following discussion will focus on the identification of major
      and minor clinical features of the disease and review the spectrum of immune
      dysregulation that is frequently seen with these patients. The primary focus of
      this review will be directed at the identification of treatment options available
      to allergists within the published practice guidelines of the American Academy of
      Dermatology and practice guidelines that are currently being developed by the
      American Academy of Allergy & Immunology. Atopic dermatitis is an "itch which
      rashes and not a rash which itches" and therefore, any patient treatment program
      should address the multiplicity of potential trigger factors that provoke this
      itching. These factors include heat, humidity, and perspiration, in addition to
      the ingestion of certain food allergens and the topical exposure to both dust
      mite antigen and animal dander. Recent studies suggest that the pathogenesis of
      allergic disease entails a complex inflammatory process in which the TH2
      lymphocyte might play a major role in shifting the immune response in favor of
      disease. Accordingly, recent immunomodulating treatments, such as interferon
      gamma and cyclosporine, might offer therapeutic options to the physician beyond
      the standard topical forms of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721075
TI  - Therapeutic indications and rationale for theophylline in the management of
      asthma.

PMID- 7721076
TI  - The beta-2 adrenergic receptor and its agonists.
AB  - The beta 2 adrenoceptor has been cloned and sequenced, and details of how agonist
      stimulation ultimately results in clinically evident effects are now known.
      Receptor desensitization by agonist is an almost universal process that can be
      prevented and reversed by corticosteroids. Although immunologic mechanisms appear
      to prevail in asthma, beta 2 receptor dysfunction may be important in some
      circumstances. Many receptor agonists are available for asthma therapy, including
      a new generation of long acting agents (such as salmeterol) with duration of
      action of 12 hours or more. Statistical links between beta agonist use and asthma
      mortality or morbidity warrant careful examination for clinical relevance, but
      may not be dismissed. Beta agonists are relatively safe and clearly effective in
      asthma, but anti-inflammatory management (including allergen avoidance and
      immunotherapy when appropriate) is indicated in patients who require chronic
      therapy.

PMID- 7721077
TI  - Active immunization: how many shots should a child endure?

PMID- 7721078
TI  - Human mast cell heterogeneity.
AB  - Mast cell neutral proteases are the most precise markers of heterogeneity among
      human mast cells. Two types of human mast cells have been recognized. MCTC cells
      contain tryptase together with chymase, cathepsin-G like protease, and mast cell
      carboxypeptidase; MCT cells contain tryptase, but lack the other neutral
      proteases present in MCTC cells. All mast cells develop from hemopoietic stem
      cells. In vitro procedures for studying mast cell growth have been developed,
      using the major human mast cell growth factor, stem cell factor (SCF, also called
      Kit-ligand). Cultures of hemopoietic progenitor cells in the presence of SCF
      alone result in selective differentiation to mast cells. The same progenitor
      cells can be induced to differentiate into other lineages when SCF is used with
      various lineage-specific colony-stimulating factors such as erythropoietin for
      erythrocytes. Mast cell development from hematopoietic progenitors may represent
      a "default pathway," occurring optimally in a permissive microenvironment such as
      skin, bowel, and lung. The presence or absence of certain cytokines in blood and
      bone marrow may create a non-permissive environment, thus the absence of
      granulated mast cells in such locations.

PMID- 7721080
TI  - Management of inflammation in allergic asthma (IRINE symposium). Immunology
      Research Institute of New England.
AB  - Allergic inflammation as a cause of asthma is now well recognized. New methods of
      identification of allergen-specific IgE including improved in vitro technologies
      will require optimization of the lowest threshold for the detection of allergen
      specific IgE in order to maximize sensitivity without loss of specificity, thus
      allowing for significant enhancement in a clinical setting for determination of
      allergen-specific IgE levels. New concepts of allergic inflammation include the
      recognition that significant histologic changes may occur even in the mildest
      allergic patients. Thus, early intervention with antiinflammatory therapies
      including corticosteroids or inhaled nedrocromil sodium appears clearly warranted
      based on these early pathological changes occurring in asthmatic individuals.
      Inhaled corticosteroids have been demonstrated to prevent pathological changes
      that otherwise occur in asthmatic patients whose sole therapy is use of inhaled
      B2 agonist. Corticosteroids have also been noted to be successful in the
      prevention of progression of pathological changes including the development of
      bronchiectasis in asthmatic patients with allergic bronchopulmonary fungoses.
      Allergen-specific immunotherapy may be successfully used in selective asthmatic
      patients allergic to pollen, dust mite, or certain mold allergens including
      Alternaria. Immunotherapy appears to be most useful in those patients who are
      allergic to one rather than many allergens and whose asthma is not associated
      with other significant precipitating factors such as chronic rhinosinusitis or
      aspirin sensitivity. The risk of systemic reactions to allergen immunotherapy in
      the asthmatic patient is significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721079
TI  - Use of intravenous immunoglobulin (IVIG) therapy in adults.
AB  - Although intravenous immunoglobulin (IVIG) has primarily been recognized as
      useful in patients with antibody deficiencies, it continues to be used for an
      ever-expanding list of conditions. In addition to antibody replacement, IVIG may
      act as an immune modulator in certain autoimmune and inflammatory conditions. Its
      use should be carefully weighed against the high cost of the product. In
      conditions where it appears to be useful, controlled studies are necessary to
      prove its efficacy and its cost benefits.

PMID- 7721081
TI  - Detection limits and receiver operating characteristic curve analysis in the
      evaluation of specific IgE assays.
AB  - One of the major sources of uncertainty and controversy in allergy testing is the
      definition and clinical significance of a positive test result in the low assay
      range. Use of analytical detection limit theory can guide the diagnostic allergy
      laboratory director in setting a lower assay cutoff and in the evaluation of the
      recommended cutoff by the manufacturer of the assay. Several methods for
      calculating lower limit of detection are applicable to specific IgE assay
      methods. Receiver operating characteristic (ROC) curves illustrate the
      relationship between statistical sensitivity and specificity as cutoffs are
      adjusted, and statistical analysis of ROC curves is an invaluable aspect of the
      comparative performance evaluation of two or more assays relative to an
      independent standard such as skin testing.

PMID- 7721082
TI  - Pathology of asthma.
AB  - Appreciation of the early damage that occurs to the respiratory epithelium has
      been limited by the use of autopsy specimens from fatally stricken asthmatics as
      a source of representative specimens. The use of bronchoscopy to obtain specimens
      from patients early in the course of their asthma has allowed a new understanding
      of the evolution of pathological changes that occur in asthma. Newly diagnosed,
      mild asthmatics have been shown to have bronchial goblet cell hyperplasia in
      addition to increased numbers of mast cells and eosinophils in the respiratory
      epithelium, and increased eosinophil granule protein deposition within the lamina
      propria. Endothelial gaps in postcapillary venules are greater in asthmatic
      airways, suggesting that increased plasma transudation may contribute to the
      known epithelial cell shedding characteristic of asthma attacks. Asthmatic
      inflammation, even early in the course of the disease, includes vascular
      permeability changes, inflammatory cell infiltration, epithelial cell shedding,
      and goblet cell hyperplasia, replacing the normal ciliated epithelium. Current
      investigation evaluating the effects of asthmatic inflammation on epithelial cell
      attachment to each other and to the extracellular matrix molecules regulated by
      adhesion glycoproteins will likely enhance further the understanding of the
      pathological changes that occur within the asthmatic airway.

PMID- 7721083
TI  - Specific immunotherapy in asthma.
AB  - There is a growing appreciation of asthma as an inflammatory disease.
      Immunotherapy may play a role in modulating immunologic responses including
      inflammatory mediator production from cells involved in asthma. Studies of pollen
      sensitive asthma have demonstrated beneficial effects of specific immunotherapy
      for grass, birch, and ragweed pollen-induced asthma. However, risk of systemic
      reactions exists, especially when specific immunotherapy is administered during
      the specific allergen season. House dust mite immunotherapy has benefitted
      asthmatic children more than adults. Patients having unstable pulmonary function
      may be at the highest risk of having systemic reactions to such immunotherapy.
      Animal dander immunotherapy and immunotherapy for molds including Clasdosporium
      and Alternaria may improve selected asthmatic patients. Avoidance of the
      offending allergen is still, however, the preferred mode of treatment of allergic
      asthma.

PMID- 7721084
TI  - Diagnosis and management of allergic bronchopulmonary aspergillosis.
AB  - Early diagnosis and treatment is essential for patients afflicted with
      bronchopulmonary aspergillosis (ABPA). Inflammatory damage to the airways may be
      significantly reduced through use of corticosteroids. Without treatment,
      bronchiectasis causing permanent anatomic alteration of the airways may occur.
      ABPA should be considered in any asthmatic who requires oral corticosteroids and
      has recurrent pulmonary infiltrates. Evaluation should include determination of
      total serum IgE, which generally exceeds 1000 ng/mL in patients with ABPA.
      Disease categorization of ABPA patients may be made according to radiographic and
      clinical considerations into five stages. The treatment choice for ABPA is
      prednisone, although inhaled corticosteroids including beclomethasone
      dipropionate may also be used in long-term asthma management. Successful therapy
      of ABPA is typically associated with a decline in total serum IgE, subsequent
      exacerbations often being associated with elevation in total serum IgE. Allergen
      avoidance is essential for the ABPA patient, as exposure to heavy concentrations
      of fungi may precipitate disease exacerbation.

PMID- 7721085
TI  - Quantitation of matrix Gla protein mRNA by competitive polymerase chain reaction
      using glyceraldehyde-3-phosphate dehydrogenase as an internal control.
AB  - Matrix Gla (gamma-carboxyglutamic acid) protein (MGP) is a vitamin-K-dependent
      extracellular matrix protein. A method was developed to quantitate MGP mRNA based
      on competitive polymerase chain reaction following reverse transcription
      (competitive RT-PCR). The MGP cDNA was coamplified with a mutant MGP cDNA
      (competitor). The ratio of MGP to competitor after the PCR reaction was compared
      to standards to determine the amount of MGP mRNA in RT samples. MGP mRNA in as
      little as 3.125 ng total RNA was accurately quantitated and was far more
      sensitive than RNA hybridization methods. To control for variations due to sample
      preparation, a second competitive RT-PCR was developed to measure the
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA from the same sample as an
      internal control. Thus, the amount of MGP is normalized to the amount of the
      housekeeping gene GAPDH. The accuracy, sensitivity and ease of this new method
      enables rapid mRNA quantitation without blotting, hybridization or
      autoradiography. The method is particularly advantageous for MGP mRNA measurement
      from a small amount of sample. Using this assay, we established that MGP mRNA
      increases approx. fivefold with co-treatment of retinoic and ascorbic acids.

PMID- 7721086
TI  - New vectors for manipulation and selection of functional yeast artificial
      chromosomes (YACs) containing human DNA inserts.
AB  - A set of fragmentation vectors is described which produce a deletion series of
      smaller yeast artificial chromosomes (YACs) from a larger parent YAC with the
      insertion of a eukaryotic selectable marker. In addition, new vectors were
      designed to permit integration of the genes encoding neomycin (neo) or hygromycin
      B (hyg) resistance into YACs containing inserts of human DNA. All these vectors
      are compatible with the yeast host strain AB1380, in which most human genomic YAC
      libraries are maintained. Linearized vector DNA is used to transform yeast cells
      in which homologous recombination between human DNA in the YAC and the Alu
      sequence in the fragmentation or integrating vector produces terminal deletions
      from the acentromeric (URA3) end of the YAC or insertion of the vector into the
      YAC, respectively. A set of directional deletions of a YAC is useful for genomic
      mapping, restriction analysis and functional measurements of large chromosomal
      regions. The neo and hyg eukaryotic markers permit the study of gene function
      after introduction of deleted YACs into mammalian cells. Transformation of YACs
      with the fragmentation vectors resulted in fragmentation in 21-46% of the clones
      examined; transformation with the integrating vector resulted in integration in
      46% of the clones examined.

PMID- 7721087
TI  - A hox/hom homeobox gene in sponges.
AB  - The hox/hom homeobox genes code for DNA-binding proteins that confer positional
      information during animal development; these genes have been found in a wide
      range of triploblasts and in cnidarians. We report here the identification of a
      hox/hom gene and two other homeobox genes in the genomes of sponges. This finding
      extends the detection of hox/hom genes to the lowest metazoan phylum and suggests
      a monophyletic origin of the kingdom Animalia. Because, in culture, sponge cells
      quickly reaggregate, differentiate and construct tissue after disaggregation,
      they can provide a useful model system for characterization of the basic roles of
      homeobox genes in the control of cellular differentiation.

PMID- 7721088
TI  - Screening and sequence determination of a cDNA encoding the human brain 4
      aminobutyrate aminotransferase.
AB  - A human brain cDNA library constructed in the lambda ZAP II vector was screened
      using a fragment of pig brain cDNA encoding 4-aminobutyrate aminotransferase
      (pGaba-t). A cDNA that encodes the human brain Gaba-t (hGaba-t) has been isolated
      from the library and sequenced. Using the GenBank and EMBL databases, comparison
      of the predicted amino-acid sequence of hGaba-t with the pig enzyme revealed
      95.4% homology.

PMID- 7721089
TI  - Cloning and transient expression of genes encoding the human alpha 4 and beta 2
      neuronal nicotinic acetylcholine receptor (nAChR) subunits.
AB  - Partial cDNA clones generated by RT-PCR were used as probes to clone the cDNAs
      encoding the human alpha 4 and beta 2 neuronal nicotinic acetylcholine receptor
      (nAChR) subunits. The 2.1-kb alpha 4 cDNA shows 84 and 76% identity to the rat
      and chicken cDNA sequences, respectively. The deduced amino-acid sequence shares
      89 and 84% similarity, respectively, with the corresponding rat and chicken
      proteins, with most of the divergence occurring in the cytoplasmic domain. The
      1721-nucleotide beta 2 sequence was identical to the human beta 2 sequence
      previously reported. Transfection of the alpha 4 and beta 2 clones into HEK293
      cells resulted in the formation of binding sites that display high affinity
      towards [3H] cytisine, a characteristic of the alpha 4 beta 2 subtype produced in
      vivo.

PMID- 7721090
TI  - High-level production of a human membrane protein in yeast: the peripheral-type
      benzodiazepine receptor.
AB  - The human peripheral-type benzodiazepine receptor (PBR) has been produced in
      Saccharomyces cerevisiae where it retains its pharmacological properties [Riond
      et al., Eur. J. Pharmacol. 208 (1991) 307-312]. As the rate of production was
      low, we analysed the mRNA level, the effect of variation of the 5' sequence and
      the production in mitochondria. Translation rather than transcription or
      targeting was found to be the main limiting factor. We were able to produce a
      chimeric PBR, with an N-terminal extension, to a very high level in the yeast
      mitochondrial membrane.

PMID- 7721091
TI  - Comparison of repetitive elements in the third intron of human and rodent
      mitochondrial benzodiazepine receptor-encoding genes.
AB  - The third intron of the mitochondrial benzodiazepine receptor (MBR)-encoding gene
      was sequenced from hamster, mouse and human. The rodent species were found to
      include an Alu-like sequence, as was first discovered in the rat gene.
      Differences with the rat intron were evident by an insertion of an additional B1
      element in the hamster and the introduction of a complete and two partial B2
      sequences in the mouse intron. The human intron contained a cluster of four Alu
      sequences; however, all of these repetitive elements were found to be in the
      opposite orientation relative to the Alu-like sequence present in the rodent
      genes. These findings support the possibility that the rodent Alu-like sequence
      is a remnant of a retropositional insertion in this gene prior to the divergence
      of rodent species. Because the human intron does not contain the same Alu
      remnant, it cannot be concluded that the rodent sequence represents an insertion
      of a primordial Alu element prior to the divergence of rodent and primate
      lineages.

PMID- 7721092
TI  - Structure, sequence and location of the UQCRFS1 gene for the human Rieske Fe-S
      protein.
AB  - We have identified and studied the chromosomal location of the human Rieske Fe-S
      protein-encoding gene UQCRFS1. Mapping by hybridization to a panel of
      monochromosomal hybrid cell lines indicated that a UQCRFS1 partial cDNA was
      derived from either chromosome 19 or 22. By screening a human chromosome 19
      specific genomic cosmid library with a probe from this cDNA sequence, we
      identified a corresponding cosmid. Portions of this cosmid were sequenced
      directly. The exon, exon:intron junction and flanking sequences verified that
      this cosmid contains the genomic locus. Fluorescent in situ hybridization (FISH)
      was performed to localize this cosmid to chromosome band 19q12.

PMID- 7721093
TI  - Cloning, sequencing and localization to chromosome 11 of a cDNA encoding a human
      opioid-binding cell adhesion molecule (OBCAM).
AB  - Oligodeoxyribonucleotide (oligo) primers derived from rat opioid-binding cell
      adhesion molecule (OBCAM)-encoding cDNA sequence were used to amplify a 403-bp
      fragment from a human brain cDNA library using the polymerase chain reaction
      (PCR). The fragment was cloned, sequenced and used as a hybridization probe to
      screen the library. lambda plaque clones were isolated which contained a 1.5-kb
      cDNA fragment, including a complete open reading frame (ORF) of 1038 bp. Sequence
      analysis of the ORF revealed 93% identity to the rat OBCAM cDNA at the nucleotide
      level, and the deduced amino-acid sequences shared 98% identity. Percentages of
      identity between human and bovine OBCAM ORFs were within 2% of these values.
      OBCAM was mapped to human chromosome 11 by hybridizing the probe with a somatic
      cell hybrid panel.

PMID- 7721094
TI  - Identification of a GATA motif in the cardiac alpha-myosin heavy-chain-encoding
      gene and isolation of a human GATA-4 cDNA.
AB  - In an attempt to identify the cardiac-specific genes regulated by the
      transcription factor GATA-4, we have identified a putative GATA-binding site
      located within the 5' flanking sequence of the human cardiac alpha-myosin heavy
      chain-encoding gene. The 23-bp sequence surrounding the core GATA-binding site is
      conserved across species. The core motif and flanking sequences of this GATA
      binding site are almost identical to that of a well-established GATA-binding site
      located within the 3' enhancer of the human beta-globin gene. Using
      electrophoretic mobility shift analysis, two distinct nuclear factors were found
      to bind specifically to this element. We have isolated a full-length cDNA clone
      for human GATA-4 (hGATA-4) by screening a human heart cDNA library. The hGATA-4
      cDNA sequence shows 85% identity with murine GATA-4 in the protein coding region.
      The deduced amino-acid sequence within the two zinc-finger DNA-binding domains of
      human GATA-4 is 100% identical with murine GATA-4. Northern blot analysis reveals
      that this 4.4-kb transcript has higher expression in adult heart than in fetal
      heart. Our results suggest that GATA-4 may regulate a set of cardiac-specific
      genes and play a crucial role in cardiogenesis.

PMID- 7721095
TI  - Overproduction and rapid purification of human fast skeletal beta troponin T
      using Escherichia coli expression vectors: functional differences between the
      alpha and beta isoforms.
AB  - Troponin T (TpnT), an essential component of the Ca(2+)-regulatory troponin
      complex, is involved in protein-protein interactions with other thin-filament
      proteins during muscle contraction in vertebrate striated muscle (VSM). The
      isoforms of TpnT are encoded by members of a multigene family which, by alternate
      splicing, produces a complex pattern of isoproteins in VSM. The functional
      domains of TpnT are only tentatively identified and structure-function analysis
      on this protein is limited due to the heterogeneity of the multiple isoforms. We
      reasoned that the overproduction and purification of a single TpnT species in
      Escherichia coli would provide an insight into these studies, besides being
      useful in crystallizing the protein. We cloned the human fast skeletal beta TpnT
      encoding cDNA (beta TpnTf) in three expression vectors. Overexpression was
      achieved in an E. coli BL21 (DE3) lysogen using a T7 RNA polymerase promoter
      based vector, pET17b. The unfused recombinant protein was purified by a simple
      and rapid procedure in a biologically active and immunoreactive form. This is the
      first successful synthesis of a complete beta TpnTf polypeptide from any species
      using an in vitro expression system. Purified human beta TpnTf, a predominant
      fetal form, was less Ca(2+)-sensitive and exhibited considerably reduced affinity
      for troponin C and tropomyosin, as compared to the rabbit fast skeletal alpha
      TpnT, a predominant adult isoform. These results provide a biochemical correlate
      to the age-related differences in Ca2+ sensitivity of tension development in
      vertebrate fast skeletal muscles.

PMID- 7721096
TI  - Cloning of a cDNA encoding a human DNA-binding protein similar to ribosomal
      protein S1.
AB  - We report the cloning of a human complementary DNA that encodes a protein which
      exhibits 36% identity and 62% similarity to Escherichia coli ribosomal protein S1
      (rpS1), including conservation of four copies of an RNA-binding domain. This
      clone was obtained by ligand-screening a lambda gt11 expression library with a
      DNA probe derived from the CYBB gene promoter. Electrophoretic mobility shift and
      Southwestern blot assays confirm DNA binding activity of the protein, which
      exhibits preferential binding to single-stranded and double-stranded DNA and a
      low binding affinity for RNA. Hence, the rpS1 protein domain previously
      identified as an RNA-binding motif can also serve as a DNA-binding domain.

PMID- 7721097
TI  - The human genes encoding renin-binding protein and host cell factor are closely
      linked in Xq28 and transcribed in the same direction.
AB  - The Xq28 chromosomal band represents a C+G-rich region onto which several genes
      have been mapped. In most cases, the exact relationship between the mapped genes
      has not yet been established, and neither the regulatory nor the spacer regions
      between the various transcription units have been defined. In the region around
      the L1CAM gene (encoding L1 cell adhesion molecule), the transcription units
      appear, from preliminary analyses, to be quite compact. By sequencing the region
      at the 3' end of the recently found host cell factor 1-encoding gene (HCFC1), we
      report that the renin-binding protein-encoding gene (RBP) major transcription
      start point lies 2763 bp downstream from the 3' end of HCFC1 and that both are
      transcribed in the same direction from the telomere to the centromere.

PMID- 7721098
TI  - Conservation of sequences between human and gorilla lineages: ADP
      ribosyltransferase (NAD+) pseudogene 1 and neighboring retroposons.
AB  - The evolution of ADP-ribosyltransferase (NAD+) pseudogene 1 (ADPRTP1) was studied
      among higher primates. When the human pseudogene was used to probe genomic DNA
      from chimpanzee, gorilla, macaque, howler monkey and lemur, a fragment from
      gorilla produced the most intense hybridization signal. The resultant
      hybridization pattern indicated a modified pseudogene structure in these primates
      relative to the human and gorilla loci. Sequence comparison of this new DNA locus
      (ADPRTP1 and surrounding retroposons) showed a nucleotide (nt) identity of 98.13%
      (over 5.8 kb) between the genomic regions of human and gorilla. A unique
      duplicated region of 30 base pairs (bp) was found in gorilla ADPRTP1, separate
      from the duplicated region (193 bp) responsible for the restriction-fragment
      length polymorphism (RFLP) previously reported in humans, and which appeared to
      represent a marker for a predisposition to cancer. An endogenous pol (gene
      encoding polymerase) related element that flanked the human pseudogene was used
      as a probe to identify a fragment from this retroviral family in New World
      monkeys. Altogether, analysis of these retroposons will provide an opportunity
      for future studies on the molecular phylogenetic relationship of higher primates.

PMID- 7721099
TI  - Cloning and characterization of the endogenous retroviral-tRNA(Glu) multigene
      family from human genomes of different racial backgrounds.
AB  - An 8.3-kb human endogenous retroviral-tRNA(Glu) (HERV-E)-encoding cDNA clone and
      a 1.5-kb genomic clone were isolated from a Chinese-derived cervical cancer cell
      line, CC7T, and their sequences determined. The former is a full-length
      endogenous retroviral cDNA containing corresponding u5-gag-pol-env-u3-r regions.
      The latter is a partial retroviral DNA segment, covering the gag and pol genes.
      Analysis of normal human DNA by Southern blot hybridization with three specific
      HERV-E molecular DNA probes revealed complex restriction-fragment length
      polymorphisms (RFLP), implying that the human genome contains diverse proviral
      structures and dispersed integration sites. The complex patterns were virtually
      identical between DNAs from African-Americans, Asians and Caucasians, with only a
      few minor variations. The data suggest that these proviral sequences were mostly
      incorporated into the human genome before racial divergence and, hence, may serve
      as markers for distinct chromosomal sites.

PMID- 7721100
TI  - Characterization of a 1.8-kb DNA segment located upstream from the human Ha-ras
      protooncogene and possibly regulating its function.
AB  - We have cloned a 1.8-kb segment of DNA just adjacent to the 5' end of the 6.4-kb
      BamHI fragment which contains the Ha-ras oncogene (ras1; GenBank notation
      HUMRASH). Electrophoretic mobility shift assays (EMSA) indicate the presence of
      multiple nuclear protein-binding sites within the 1.8-kb segment. At least three
      putative regulatory protein-binding sites have been identified in a 206-bp
      subfragment by DNase I footprint analysis. Within the subfragment containing the
      DNase-protected regions, there is also a segment containing a number of consensus
      sequences for DNA-binding proteins and two sub-sequences that exhibit strong
      sequence homology to at least two previously characterized enhancers. These data
      suggest that a novel set of regulatory elements may lie as far as 2 kb upstream
      from the normal Ha-ras transcription start points.

PMID- 7721101
TI  - Isolation of a murine cDNA clone encoding Rab19, a novel tissue-specific small
      GTPase.
AB  - Using a rapid amplification of cDNA ends (RACE) cloning approach, we have
      isolated a cDNA clone encoding Rab19, a novel small GTPase of the Rab subfamily
      contained within partial sequences previously described [Chavrier et al., Gene
      112 (1992) 261-264]. Northern blot analysis of the distribution of the rab19 mRNA
      in various adult mouse tissues and NIH 3T3 fibroblasts revealed that rab19 is
      expressed in a tissue-specific manner. The rab19 transcript was detected at high
      levels in intestine, lung and spleen, and at a lower level in kidney. In
      contrast, liver, brain, heart and NIH 3T3 fibroblasts contain only very little or
      no detectable rab19 mRNA. Therefore, Rab19 is likely to represent a novel tissue-
      or cell type-specific small GTPase.

PMID- 7721102
TI  - Complementary DNA characterization and chromosomal localization of a human gene
      related to the poliovirus receptor-encoding gene.
AB  - The human poliovirus (PV) receptor (PVR) is a member of the immunoglobulin (Ig)
      superfamily with unknown cellular function. We have isolated a human PVR-related
      (PRR) cDNA. The deduced amino acid (aa) sequence of PRR showed, in the
      extracellular region, 51.7 and 54.3% similarity with human PVR and with the
      murine PVR homolog, respectively. The cDNA coding sequence is 1.6-kb long and
      encodes a deduced 57-kDa protein; this protein has a structural organization
      analogous to that of PVR, that is, one V- and two C-set Ig domains, with a
      conserved number of aa. Northern blot analysis indicated that a major 5.9-kb
      transcript is present in all normal human tissues tested. In situ hybridization
      showed that the PRR gene is located at bands q23-q24 of human chromosome 11.

PMID- 7721103
TI  - Construction of a human DNA library in a circular centromere-based yeast plasmid.
AB  - The construction of a human DNA library in a centromere-based circular yeast
      plasmid is described. The vector contains the yeast CEN3 sequence, the URA3 gene
      for propagation in yeast and a hygromycin-resistance gene (HyR) for selection in
      mammalian cells. The library consists of 64,000 members with an average insert
      size of 150 kb, with some members containing inserts of > 1 Mb. We calculate that
      the library contains three human genome equivalents of DNA. Clones can be
      identified by a PCR-based screening of DNA pools from individual colonies that
      have been stored in microtiter wells.

PMID- 7721104
TI  - A novel pituitary transcription factor is produced by alternative splicing of the
      human GHF-1/PIT-1 gene.
AB  - An alternative splice acceptor site in intron 1 of the human GHF-1/PIT-1 gene was
      sequenced. The use of this splice site is responsible for a 78-bp in-frame
      insertion upstream from exon 2 and leads to the hGHF-2/PIT-2 cDNA detected in
      normal human pituitary.

PMID- 7721105
TI  - Tandem arrangement of human genes for interleukin-4 and interleukin-13:
      resemblance in their organization.
AB  - The genes encoding human interleukin-4 (IL-4) and interleukin-13 (IL-13) are
      located on segment q23-31 of chromosome 5 and encode two multifunctional
      lymphokines with some common functions. We have cloned 72 kb of human genomic DNA
      that contain IL-4 and IL-13 and their flanking sequences, and constructed a
      restriction map of this region. Using Southern analysis, we have shown that IL-13
      is located 12 kb 5' to IL-4 and linked in a 'tail-to-head' fashion. We have also
      determined the complete nucleotide sequence of the DNA fragment (about 4.8 kb)
      containing IL-13 and its 5' flanking regulatory region (2.1 kb) with a 'CpG
      island'. We identified potential binding sites for a different transcription
      factors in the 5' flanking region and in the first intron of IL-13. Comparison of
      IL-13 and IL-4 revealed considerable similarity in the structural organization of
      these genes and also many potential binding sites for transcription factors
      common to both genes: AP1, AP2, AP3, PEA3, HRE, TCF-1, GATA-3 and the interferon
      inducible and enhancer elements. These results, along with the similarity in
      functional activity of IL-4 and IL-13 suggests that their expression may be
      coregulated.

PMID- 7721106
TI  - The human pancreatitis-associated protein (PAP)-encoding gene generates multiple
      transcripts through alternative use of 5' exons.
AB  - The nucleotide (nt) sequence of the human cDNA encoding PAP, a pancreatic
      secretory protein induced during acute pancreatitis, was found to be identical
      with that of a gene activated in human primary hepatocellular cancer, designated
      HIP. To obtain insight into the expression of PAP/HIP, we characterized the gene
      organization, especially focusing on the 5'-flanking region, and found that it
      spans about 3 kb and is composed of six exon. Exon 1 encodes the 5'-noncoding
      sequence and exon 2 consists of three miniexons, 2a, 2b and 2c; the common exon
      2c encodes the sequence including the start codon. Analysis by RT-PCR revealed
      the presence of at least three different types 5'-ends of human PAP/HIP
      transcripts which were derived from alternative use of 5'-exons. Although all
      three types of transcripts were expressed in both normal small intestine and
      pancreas, their gene expression was increased ectopically in gastric cancer,
      hepatocellular cancer and pancreatic acinar cell carcinoma. Furthermore,
      significant differences among the transcript types were detected between normal
      and tumor tissues, and especially between gastric and hepatocellular cancers,
      suggesting that PAP/HIP expression may vary with differences in 5'-alternative
      splicing.

PMID- 7721107
TI  - Cloning of a human gene potentially encoding a novel matrix metalloproteinase
      having a C-terminal transmembrane domain.
AB  - Matrix metalloproteinases (MMPs) play key roles in tissue remodeling during
      physiological and pathological processes by degrading various extracellular
      matrix (ECM) components. Although nine distinct MMPs have been characterized by
      cDNA cloning, there are thought to be more corresponding to the complexity of the
      ECM. MMP genes expressed in human tissues and cell lines were analyzed by the
      polymerase chain reaction (PCR) using degenerate primers that corresponded to the
      conserved amino acid (aa) sequences of the MMPs. One isolated complementary DNA
      (cDNA) fragment had sequence homology to the reported MMPs, but was otherwise
      unique. A human placenta cDNA library (Clontech) was screened using the fragment
      as a probe and a 3.4-kb cDNA fragment containing a long open reading frame
      (potentially encoding 582 aa) was isolated. The putative gene product had a
      common domain structure and the conserved sequence of a MMP, but it had a unique
      transmembrane (TM)-like structure at the C terminus. It should, therefore, be an
      TM protein, whereas all the other reported MMPs are secretory proteins. Thus, the
      gene is thought to be the first of a new subclass of MMPs whose products are
      potentially expressed on the cell surface.

PMID- 7721108
TI  - Human isoleucyl-tRNA synthetase: sequence of the cDNA, alternative mRNA splicing,
      and the characteristics of an unusually long C-terminal extension.
AB  - The human isoleucyl-tRNA synthetase (IRS)-encoding cDNA, whose primary structure
      we report here, has an open reading frame (ORF) which encodes a protein of 1262
      amino acids (aa) with strong homology to IRS from yeast (53.5%) and Tetrahymena
      (51.0%) and contains all the major consensus motifs of class-I hydrophobic amino
      acyl-tRNA synthetases (aaRS; MRS, LRS, VRS, IRS). However, the human enzyme has
      an unusually long C-terminal extension composed, in part, of a twice-repeated
      motif which shows no homology to any reported protein. We also report the
      presence of a coiled-coil-like motif in the C-terminal half of the protein. The
      mRNA has an additional exon in the 5'-untranslated region (UTR) which is
      alternatively spliced, giving rise to two types of mRNA, both of which are
      expressed in several human tissues. The longer of the two transcripts contains
      predicted secondary structure in the 5'-UTR which may reduce the translational
      efficiency of this mRNA. Two possible regulatory elements in the 5'-UTR, an
      interferon-stimulated response element (ISRE)-like sequence and a short ORF, have
      been identified. Because human IRS has previously been shown to be the target of
      antibodies in autoimmune disease, we discuss the role of protein structural
      features in the development of an autoimmune response to IRS.

PMID- 7721109
TI  - Sequence of a cauliflower mosaic virus strain infecting solanaceous plants.
AB  - The complete nucleotide sequence (8031 bp) of the DNA of cauliflower mosaic virus
      (CaMV) strain B29 is reported. This strain is unusual, since it infects both
      cruciferous and solanaceous plants. So far, from data of sequence comparisons
      between B29 and other CaMV strains there is no evidence for any obvious
      correlation between host range and distinct sequence features.

PMID- 7721110
TI  - Cloning of a canine cDNA homologous to the human transforming growth factor-beta
      1-encoding gene.
AB  - A 1369-bp cDNA that encodes a homolog of the human transforming growth factor
      beta 1 (TGF-beta 1) has been isolated from canine endothelial cells using a
      combination of PCR and traditional plaque-screening methods. The deduced 390
      amino-acid sequence of the canine TGF-beta 1 precursor has 91-94% identity to
      those deduced from the previously described human and mouse TGF-beta 1 clones.

PMID- 7721111
TI  - Atrial fibrillation: an update on new management strategies.
AB  - Atrial fibrillation is a common arrhythmia that frequently results in significant
      and sometimes refractory clinical symptoms of palpitations, effort intolerance,
      and breathlessness. The clinical picture, as well as a real risk of embolism,
      make appropriate management an important priority in medical practice. Older
      strategies, such as reliance on pharmacologic therapy to control ventricular
      rate, are being displaced by newer techniques to maintain sinus rhythm. These
      techniques often involve a combination of electrical cardioversion, use of newer
      direct-acting AV nodal blocking drugs and antiarrhythmic medication, AV node
      ablation and modification procedures, and permanent pacemaker therapy. These
      newer treatment approaches--together with anticoagulation and antiplatelet
      therapy--continue to evolve, with the goal of optimizing the lifespan and
      lifestyle of patients with this rhythm disorder.

PMID- 7721112
TI  - Gout or 'pseudogout': how to differentiate crystal-induced arthropathies.
AB  - Gout is an inflammatory joint disease that primarily affects middle-aged men and
      postmenopausal women. It is characterized by severe pain and erythema in the big
      toe and other affected joints. Acute gout may be triggered by diuretics, aspirin,
      minor trauma, or acute illness. The presence of monosodium urate crystals within
      phagocytes from synovial fluid aspirates is almost always diagnostic. Calcium
      pyrophosphate deposition disease ("pseudogout") usually affects larger joints and
      often follows trauma, surgery, or ischemic heart disease. Microscopic examination
      of crystals under compensated polarized light is used to differentiate gout and
      pseudogout. Disorders involving basic calcium phosphate are often more difficult
      to diagnose and treat but are also less likely to be disabling.

PMID- 7721113
TI  - Detection and treatment of hypothyroidism and Graves' disease.
AB  - The clinical presentations of thyroid disorders are often subtle in older adults
      and may be confused with "normal" aging. To avoid delay in diagnosis, we
      recommend routine TSH screening of all patients age 60 and older in the primary
      care practice. With hypothyroidism, pursue treatment cautiously; start with small
      doses of levothyroxine and closely monitor serum TSH values. When hyperthyroidism
      is caused by Graves' disease, begin symptomatic therapy with a beta blocker or
      antithyroid drugs, followed by definitive thyroid ablation with radioiodine.
      Surgical treatment may be indicated if a goiter causes compressive symptoms.

PMID- 7721114
TI  - Elder abuse and neglect: how to recognize warning signs and intervene.
AB  - Elder mistreatment, whether abuse or neglect, can be classified as physical,
      psychological, or financial/material. Several types of mistreatment may occur
      simultaneously. Abuse occurs across all socioeconomic, racial, and religious
      lines. Risk factors include a history of mental illness or alcohol/drug abuse, a
      family history of violence, isolation of the victim, and recent stressful events
      in the life of the victim or abuser. For the physician the patient workup
      includes a careful history and physical exam, including cognitive evaluation. Ask
      about living arrangements, financial status, social supports, and emotional
      stressors. If possible, observe the interaction between the patient and family
      member or caregiver. Helpful resources include your state's Office of Protective
      Services and the American Medical Association's recently published guidelines for
      diagnosis and treatment of elder abuse and neglect.

PMID- 7721115
TI  - What's geriatrics? Six secrets this pediatrician already knows.

PMID- 7721116
TI  - Put research on the nation's agenda.

PMID- 7721117
TI  - Measurement of basal tear turnover using a standardized protocol. European
      concerted action on ocular fluorometry.
AB  - BACKGROUND: The aim of this study was to compare basal tear turnover values of
      healthy volunteers in different countries. METHODS: Healthy volunteers aged
      between 20 and 70 years were selected in three European cities. Basal tear
      turnover values were calculated according to a standardized protocol from the
      decay of the fluorescein concentration in tears after instillation of 1
      microliters drop of fluorescein in the conjunctival sac. Fluorescein
      concentration was measured with identical commercial fluorophotometers. A mono
      exponential decay of fluorescein was assumed to represent basal tear flow.
      RESULTS: The mean tear turnover values were 13.1%/min +/- 4.6 SD (n = 4),
      16.0%/min +/- 5.2 SD (n = 24) and 17.5%/min +/- 3.4 SD (n = 20) in Clermont
      Ferrand (France), Leiden (The Netherlands) and Madrid (Spain), respectively. The
      differences between the values were not significant (Mann-Whitney test P > 0.09).
      CONCLUSIONS: The tear turnover in the different cities was similar. The methods
      used were simple and the software easy to use.

PMID- 7721118
TI  - Efficacy of apraclonidine ophthalmic solution (Iopidine) in presumed silicon oil
      induced glaucoma and primary open-angle glaucoma.
AB  - BACKGROUND: This pilot study evaluated the acute effects of topical ocular
      apraclonidine 1% (Iopidine) in 10 patients with presumed silicone oil-induced
      secondary glaucoma (SOIG) and in 10 patients with high-pressure primary open
      angle glaucoma (POAG) despite maximum tolerated medical therapy. METHODS:
      Intraocular pressure (IOP) measurements were carried out before and 1, 2 and 3 h
      after a single drop of apraclonidine. RESULTS: Patients with SIOG presented with
      a mean IOP of 30.0 +/- 2.8 mmHg, which was reduced to 21.7 +/- 2.9 mmHg (P <
      0.001) after 1 h, to 20.4 +/- 2.3 mmHg (P < 0.001) after 2 h and to 20.0 +/- 2.5
      mmHg (P < 0.001) after 3 h. In the POAG group, IOP was reduced from 25.9 +/- 1.9
      mmHg before treatment to 18.9 +/- 1.4 mmHg after 1 h (P < 0.001), 17.7 +/- 1.2
      mmHg after 2 h (P < 0.001) and 16.9 +/- 0.9 mmHg after 3 h (P < 0.001). There
      were no significant changes in blood pressure or pulse rate. CONCLUSION: This
      study confirmed the activity of apraclonidine as an IOP suppressant.

PMID- 7721119
TI  - Activated T lymphocytes in epiretinal membranes from eyes of patients with
      proliferative diabetic retinopathy.
AB  - BACKGROUND: To investigate the potential contribution of immune-mediated
      processes to the development of proliferative diabetic retinopathy (PDR), an
      immunohistochemical study was undertaken to characterize the infiltrating immune
      cells in epiretinal membranes from the eyes of patients with PDR. METHODS: A
      total of 18 PDR epiretinal membrane specimens obtained surgically from pars plana
      vitrectomy were studied by using a panel of monoclonal antibodies against T
      lymphocytes (CD4 and CD8), interleukin-2 (IL-2) and interleukin-2 receptors (IL
      2R). RESULTS: Twelve of 18 specimens (67%) contained CD4-positive cells and 13 of
      18 (73%) contained CD8-positive cells. IL-2 was found in 12 of 18 samples (67%),
      of which 11 also contained CD4-positive cells, and IL-2R was detected in 10 of 18
      membranes (56%), of which 9 contained CD4-positive cells and released IL-2. Most
      of the IL-2R-positive membranes were from type I diabetic patients, 40% of them
      from patients younger than 40 years. CONCLUSION: Our study demonstrated the
      involvement of activated immune cells and release of lymphokine(s) in more than
      half of the diabetic epiretinal membranes tested and revealed that the processes
      of immune responses and the biological effects of lymphokine(s) may play an
      important part in the development of epiretinal membranes of PDR, especially in
      young-onset and type I diabetes.

PMID- 7721120
TI  - The effect of chemical stability and purification of perfluorocarbon liquids in
      experimental extended-term vitreous substitution.
AB  - BACKGROUND: To determine the importance of chemical stability and purification of
      perfluorocarbon liquids (PFCLs) in experimental retinal tolerance, we tested four
      different substances as long-term vitreous tamponade: purified and nonpurified
      perfluorodecalin (PFD) and perfluoro-octyl-bromide (PFOB). METHOD: After
      mechanical vitrectomy we replaced the vitreous of 65 rabbit eyes. Five groups
      were formed; four of them received the four PFCLs, while one served as control
      and received Ringer solution. The eyes were observed clinically every week and
      examined histologically after 1, 2, 4 and 8 weeks. RESULTS: After 1 week we
      observed foam cells and intraretinal macrophages in all eyes with PFCLs. Purified
      PFD caused retinal lesions in the photoreceptor, ganglion cell and outer nuclear
      layers after only 2 weeks in the lower part of the eyes. In eyes filled with
      purified PFOB we observed more pronounced damage of the same nature. Unpurified
      substances caused severe inflammation and retinal detachment. CONCLUSION: Our
      study demonstrates that purification and chemical stability are important factors
      in retinal tolerance of PFCLs for vitreous replacement. Although purified PFD was
      tolerated by the rabbit eyes for 1 week, we cannot recommend this substance for
      short-term clinical use as a vitreous substitute.

PMID- 7721121
TI  - Passage of drugs through different intraocular microdialysis membranes.
AB  - BACKGROUND: Since drug penetration from the blood to the vitreous body is very
      poor, it is important to find means other than systemic delivery to reach
      necessary intraocular concentrations of drugs. This study represents a step in
      this direction. METHOD: Microdialysis probes implanted intraocularly in rabbits
      were perfused with different substances, mainly drugs. The substances belonged to
      three groups, antibiotics, corticosteroids and cytostatics, and were:
      benzylpenicillin and cefuroxim; triamcinolone and dexamethasone; daunomycin and 5
      fluorouracil. In addition, three substances of different molecular weights were
      tested: formic acid (MW 70), glucose (MW 189) and insulin (MW ca. 5200). RESULTS:
      When used in tracer concentrations, some lipophilic drugs stick to polycarbonate
      but not to polyamide membranes. The latter material has therefore been used in
      all intraocular perfusions. All substances except inulin were found to diffuse
      through the polyamide membrane into the vitreous at a rate of about 10-20% of the
      perfusate concentration. Membranes with different dimensions and the above
      mentioned two materials have also been screened for their transport properties in
      vitro. No differences were found between the two membrane materials,
      polycarbonate and polyamide. The net dialysis is strongly dependent on the probe
      geometry. CONCLUSIONS: We have shown that the above-mentioned substances
      penetrate into the vitreous body of rabbits through an implanted microdialysis
      membrane. This is of importance for the development of new means of intraocular
      drug administration.

PMID- 7721122
TI  - Deamination of 3-hydroxykynurenine in bovine lenses: a possible mechanism of
      cataract formation in general.
AB  - BACKGROUND: 3-Hydroxykynurenine, a metabolite of tryptophan, acts as UV filter in
      the human lens. In this study, we looked for this substance and its metabolites
      in young and old bovine lenses, because of their possible role in the formation
      of cataract. METHODS: The substances were detected by HPLC analysis. The
      fluorescent substance formed from 3-hydroxykynurenine was characterized by thin
      layer chromatography followed by reaction with ninhydrin, UV and fluorescence
      spectrum analysis, and atom bombardment for molecular mass determination. The
      kynurenine aminotransferase activity was determined by the method of Tobes.
      RESULTS: 3-Hydroxykynurenine was detected at concentrations of 0.07, 0.19, and
      1.14 micrograms/g of tissue in the bovine iris/ciliary body, retina, and
      transparent bovine lenses respectively. 3-Hydroxykynurenine was deaminated in old
      bovine eyes but not in calf eyes. In old eyes, kynurenine aminotransferase
      activity was 2.7, 3.5, and 9.6 mumol/g of tissue per h in retina, iris/ciliary
      body, and lens respectively. CONCLUSION: The deamination of 3-hydroxykynurenine
      resulted in the formation of a fluorescent substance which was identified as
      oxidized xanthurenic acid. This substance, accumulating in the bovine lens and
      interacting with lens proteins, could induce cataract formation.

PMID- 7721123
TI  - Local effects of different perfluorochemical agents.
AB  - PURPOSE: To clarify whether the prolonged presence of perfluorochemicals (PFC) in
      the vitreous cavity causes oxidative tissue damage and inflammatory response of
      the retina and, if so, what the process is. METHODS: After three different
      perfluorochemicals [perfluorodecalin (C10F18), perfluorooctane (C8F18) and
      Fluosol-DA (corresponding to a 20% emulsion of 70% PFD and 30%
      perfluorotripropylamine, C9F21N)] had been in the vitreous cavity of rabbits for
      2 weeks, lipid peroxide concentration and myeloperoxidase activity in the retina
      were determined. RESULTS: Whereas only Fluosol-DA showed significant oxidative
      damage, the inflammatory activity was significantly increased in all groups.
      CONCLUSION: The increased myeloperoxidase activity and the observed oxidative
      damage of the retina seem to be the effect of both perfluorochemical-loaded
      macrophages and inflammatory-induced lipid peroxidation.

PMID- 7721124
TI  - Systemic effects of different perfluorochemical agents.
AB  - PURPOSE: An intravitreal injection of Fluosol-DA leads to a higher alteration of
      the macrophage system of the retina than perfluorooctane and perfluorodecalin
      administered by the same route. The difference may be due to different kinds of
      oxidative damage caused by the three chemicals. To test the validity of this
      assumption, the degree of cell alteration, expressed as reduction of cytoplasmic
      motility, caused by these three perfluorochemicals was examined. METHODS: Using
      the hepatic macrophage system of the rat, cell alteration was examined by
      magnetometry after intravenous application of various perfluorochemicals
      [emulsified perfluorodecalin (C10F18), perfluorooctane (C8F17Br) and Fluosol-DA
      (corresponding to a 20% emulsion of 70% perfluorodecalin and 30%
      perfluorotripropylamine, C9F21N)]. RESULTS: After administration of high doses,
      all perfluorochemicals led to cytoskeleton alteration. This alteration, expressed
      as retardation of the relaxation period of ferromagnetic iron oxide particles,
      was most pronounced after administration of Fluosol-DA. CONCLUSION: The
      compromising effect of perfluorochemicals is dose dependent and differs among the
      three compounds tested, with Fluosol-DA showing the greatest decrease in
      cytoplasmic motility.

PMID- 7721125
TI  - Reversible leukocoria associated with clinically significant diabetic macular
      edema.

PMID- 7721126
TI  - Frequency and amplitude in scotopically stimulated optokinetic nystagmus.
AB  - BACKGROUND: It was previously shown that optokinetic nystagmus (OKN) gain (eye
      velocity/target velocity) increases with increasing target luminance at a
      constant target velocity during scotopic vision. Eye velocity was defined as the
      amplitude of the eye jerk divided by the period time. The dependence of frequency
      and amplitude of eye jerks in scotopic OKN on target luminance and velocity was
      investigated in the present study. METHOD: A total of nine subjects were examined
      for OKN with various target luminance and velocities under scotopic conditions.
      Monocular OKN was elicited by a vertical grating projected in a hemisphere. The
      eye movement was recorded by DC EOG. RESULTS: It was found that when a constant
      target velocity is used, both the frequency and amplitude of eye jerks increase
      with an exponential decline as target luminance increases. The maximum frequency
      and amplitude obtained at high target luminance are independent of target
      velocity. The exponential decline constants for both frequency and amplitude
      decrease with increased target velocity. CONCLUSION: Both frequency and amplitude
      of eye jerks are responsible for changes in OKN gain when target luminance and
      velocity change.

PMID- 7721127
TI  - [Values of antipyrine test in female workers of household chemistry plants].
AB  - Statistical processing did not reveal the influence of profession, length of
      service, age of female workers of domestic chemistry factories on the values of
      antipyrine test. Labor conditions, irrespective of industrial factors, changed
      the test parameters in 39% of female workers.

PMID- 7721128
TI  - [Bioavailability of microelements and their interactions in the course of
      metabolism (review)].

PMID- 7721129
TI  - [Methods of decrease of body's exposure to nitroso compounds].

PMID- 7721130
TI  - [Current tasks of physician training in protection of children's and adolescents'
      health].

PMID- 7721131
TI  - [Daily energy expenditures and energy requirements of pupils at general education
      schools in the Republic of Uzbekistan].
AB  - Evaluation of daily anergy expenditures was made on the basis of study of
      schoolchildren's time budget and their energy expenditures at the main body
      postures and during various types of activity. The data were used for
      substantiation of the physiological energy requirements to schoolchildren of
      different age and sex. Recommendations on the rations for schoolchildren with
      consideration for age and sex were made.

PMID- 7721132
TI  - [Constitutional dependence of the parameters of physical development in
      children].
AB  - The variability of morphofunctional indices of the children's organism (10-14
      years old) is caused by the constitutional type. Body mass, chest circumference,
      bone components, total physical efficiency, highest oxygen consumption are the
      principal factors determining the constitutional type of a child.

PMID- 7721133
TI  - [Characteristics of equilibrium function in preschool children with bearing
      disorders].
AB  - The fluctuations of gravity centre projection of a child's body were studied by
      computer stabilograph. Investigations showed that children with bearing disorders
      have lower indices of static and dynamic components of balance function. This
      results should be taken into account when carrying out hygienic measures aimed at
      prevention of bearing disturbances in children.

PMID- 7721134
TI  - [Remarks on the use of of several physical values in standards of radiation
      safety, health regulations and other documents].
AB  - The levels of radioactive substances in all standard documents and special
      literature is expressed by the rate of their disintegration, which is not
      correct. The main indicator of radioactive danger is surface pollution (for
      example, in Bq/km2). But pollution of surface can be uneven and in some places
      dangerous. Recommendations to correction of the matter are offered.

PMID- 7721135
TI  - [Wounds and burns of the skin polluted by alpha irradiation in personnel of
      radiochemistry enterprises].
AB  - Records of pollution by plutonium and americium 241 of skin wounds and burns in
      the personnel of the Mayak plant in 1948-1992 are analyzed. Traumas occurred in
      286 (7.2%) workers, mechanical injuries were 84.1% of these. A high incidence of
      wound contamination was recorded in the workers engaged in mechanical processing
      of plutonium. Altogether 34.1% of injuries had alpha-radiators in residual
      amounts after debridement, though their levels did not surpass the minimal levels
      of radionuclide detection.

PMID- 7721136
TI  - [Hygienic express-diagnosis of the toxicity of drinking water disinfectants using
      biotests].
AB  - Toxicity of water treated by two disinfectants, AOKh-K and gaseous chlorine, was
      studied by biotesting on Daphnia magna, Tetrahymena pyriformis (TP) and renal
      epithelium of porcine embryo (REPE). The study showed that AOKh-K preparation is
      nontoxic and chlorine toxic for TP and REPE in concentrations 2 and 3 mg/l.

PMID- 7721137
TI  - [Toxicological and hygienic monitoring and toxico-metric assessment of
      consequences of exposure to herbicides in agricultural enterprises].

PMID- 7721138
TI  - [Effects of revolving electric fields of industrial frequency on blood system of
      laboratory animals].

PMID- 7721139
TI  - [Complex assessment of the level of human health].

PMID- 7721140
TI  - [Substantiation of criteria for standardization and complex assessment of life
      conditions in military technology objects].

PMID- 7721141
TI  - [History of school health supervision in Russia in the 1st half of the 20th
      century (75th anniversary of the 1st All-Russian Congress of Physicians on School
      Health)].

PMID- 7721142
TI  - [In memory of D. G. Oppenheim (1899-1994)].

PMID- 7721143
TI  - [Analysis of "Methodological instructions on determination of levels of
      electromagnetic fields and borders of health protective zones and zones of
      limited building in sites adjacent to television and FM broadcasting media"].

PMID- 7721144
TI  - [Hygienic aspects of Nizhnekamsk and Kuibyshev water reservoir protection under
      conditions of reclamation of irrigated deposits of non-ore building materials].
AB  - Effects of sand and gravel extraction on water quality of two reservoirs were
      assessed. Water quality was found to depend on flow velocity. Hygienic
      requirements to safe water use by population in places of such work were
      substantiated.

PMID- 7721145
TI  - [Hygienic evaluation of working conditions and indicators of health status of
      workers in poultry farms].
AB  - The main unfavourable factor of poultry farms environment is contact of workers
      with chemical disinfectants. Changes in morphofunctional, cytochemical,
      immunological parameters and higher level of morbidity were revealed in poultry
      farms. Hygienic prophylactic recommendations were made.

PMID- 7721146
TI  - [Congenital toxoplasmosis in the Poznan region].
AB  - Among 3,734 women, hospitalized for giving birth, 58.9% had a positive Toxoplasma
      serological test (DA). No clinical expression of congenital toxoplasmosis was
      observed in 4,311 newborns; seven had a false positive ISAGA test with cord
      blood. Only 24% of the women were aware of congenital toxoplasmosis and only 3%
      were serologically examined before. Health education should be intensified and
      serological tests more commonly performed especially in the risk groups.

PMID- 7721147
TI  - [Amniotic fluid index during labor in women with EPH gestosis].
AB  - Intrapartal cardiotocographic disturbances of fetal heart rate patterns, the way
      of delivery and the neonate state have been analyzed in the group of 61 women in
      labor with pregnancy complicated by EPH gestosis. The results have been compared
      with pre-labor values of amniotic fluid index (AFI) in that group. In the group
      of 30 women in labor with AFI < or = 5 cm the analysis revealed the higher
      prevalence of non stress test reactivity losses, severe variable decelerations,
      late decelerations, cesarean sections and lower birth weight in comparison with
      the group of 31 women in labor with AFI > 5 cm. The study revealed that pre-labor
      AFI value estimation is usefull in predicting possibilities of fetal compromise
      during labor in women with pregnancies complicated by EPH gestosis.

PMID- 7721148
TI  - [Trial for assessment of values: normal, threatening, and pathologic parameters
      of acid-base equilibrium in umbilical vessel blood and capillary blood in
      newborns].
AB  - A prospective study in 33 newborns infants born spontaneously at term was carried
      out. First stage labour duration was up to 10 hours while the second one was no
      longer than 60 minutes. The key criterion for newborns selection from
      physiological deliveries was a normal heart rate baseline throughout the whole
      period of labour. Acid-base parameters in umbilical blood vessels and capillary
      blood were performed on an Blood Analyzer Corning 168. The results allowed to
      define normal and pathological ranges of the analysed indicators. They may be
      used for evaluation of newborn's postnatal conditions.

PMID- 7721149
TI  - [Ultrasonographic evaluation of yolk sac in early pregnancy].
AB  - Ultrasound diagnosis of yolk sac in early pregnancy. In cross-sectional study
      pregnant patients were analyzed by means of endovaginal ultrasound. Yolk sac
      diameter was analyzed to assess its growth in early pregnancy. Linear growth of
      sac diameter was observed (at 31 day of the cycle 0.4 mm at 72nd day of the cycle
      4.8 mm).

PMID- 7721150
TI  - [Transvaginal ultrasound in evaluation of the uterine cervix during pregnancy].
AB  - 127 pregnant patients between 20 and 37 week of gestation were studied. Cervical
      estimation was done by using transvaginal ultrasonography. An accurate estimation
      was possible in all investigation patients. Statistically significant
      distinctions in uterine cervical length during pregnancy progress were noticed (p
      < 0.05). However, differences in cervical with were not perceived (p = 0.3).
      Interdependence of the duration of pregnancy upon the cervical length and width
      were calculated. Obtained findings could be applicable in preterm labor
      prognosis.

PMID- 7721151
TI  - [Hematocrit values in newborns with intraventricular hemorrhage, periventricular
      hemorrhage and periventricular leukomalacia].
AB  - The group of one hundred newborns with a birth weight from 650 to 3340 g, born
      between 24 and 41 week of pregnancy had been assessed according to the
      interdependence between hematocrit and intraventricular haemorrhage (IVH) and
      periventricular leukomalacia (PVL). The data indicate that among etiological
      factors which have the influence on prevalence and intensification of IVH and PVL
      there should be taken into consideration abnormal values of venous haematocrit in
      first hours of life. Newborns with moderate and severe degree of IVH and with PVL
      have abnormal values of haematocrit in first hours of life in 50-60%. In etiology
      of IVH and PVL greater importance have decreased than increased values of
      haematocrit.

PMID- 7721152
TI  - [Primary and secondary ovarian hypoplasia].
AB  - In 98 young women with lack of maturity, with menstrual disturbances and with
      insufficiency of the primary and secondary sexual signs an the basis of clinical
      and hormonal investigations in 61.2% the primary and in 38.8% the secondary
      ovarian hypoplasia was established. This allowed in spite of great clinical
      resemblance of the investigated persons to the proper diagnosis and to the choice
      of the suitable therapy.

PMID- 7721153
TI  - [Factors influencing the outcome of radiotherapy for endometrial tumor of the
      uterus].
AB  - Assessment of the influence of staging, age of women, type and grading of
      carcinoma of endometrium, uterus size as well as radiotherapeutic methods on 5
      year survival was undertaken. The study was performed on 227 patients with Ist,
      IInd, IIIrd stage of carcinoma in whom only radiotherapy was applied. All of the
      mentioned factor have prognostic value, but the most important is staging and
      grading. Brachytherapy is also important prognostic factor.

PMID- 7721154
TI  - [The influence of different cryopreservation buffers on the fertilizing ability
      of human sperm "in vitro". II. Evaluation of the fertilizing potential of human
      sperm after cryopreservation].
AB  - We tried to define a potential ability of human spermatozoa for fertilization
      after 3 month preservation of samples in a liquid nitrogen. The functional test
      were applied: penetration of sperm to cervical mucus ("Penetrak") and sperm
      penetration to hamster zona-free oocytes. We would like to emphasize that
      presented way of cryo-preservation in 3 selected media with fast cooling of
      samples allow to maintain fertilizing ability of spermatozoa and subsequent
      insemination.

PMID- 7721155
TI  - [Pregnancy behavior and human sex education].
AB  - Pregnancy as an notion used in both, positive and negative meaning, has the great
      importance in the human sexual education and as an consequence influences on
      possibility of conception and pregnancy development in adult women as an natural
      obligation of human being delivery.

PMID- 7721156
TI  - [Kidney tumor imitating an ovarian tumor].

PMID- 7721157
TI  - [The course of induced labor after use of intracervical extra-amniotic
      prostaglandin F2 alpha in pregnant patients with EPH gestosis].
AB  - The aim of our study was to assess the efficacy of labor induction among patients
      affected by EPH gestosis after intracervical extra-amniotic insertion of 15 mg
      PGF2 alpha in methyl-cellulose gel. We concluded that PGF2 alpha when given
      intracervically in methyl-cellulose gel is a highly effective inducer of cervical
      ripening process as well as subsequent uterine contractions, too. It should be
      stressed that in no case did we find blood pressure increase after such therapy.

PMID- 7721158
TI  - [Laparoscopic hysterectomy with vaginal extraction].
AB  - In the paper authors present 30 laparoscopic hysterectomy made during 5 month
      (november 1992 till march 1993). Indications to laparoscopic hysterectomy were:
      myomata uteri, recurrent metrorrhagia and CIN III. The middle duration time of
      operation was 153 min. and the middle blood loss during operation was 122 ml. 28
      patients during first control after operation felt well. In 1 patient
      intraoperative injury of urine bladder was noted and in next injury of left
      ureter.

PMID- 7721159
TI  - [Personal observations concerning surgical treatment of urinary stress
      incontinence in women].
AB  - Own observations concerning surgical treatment of urinary stress incontinence
      based upon the clinical follow-up of 82 treated women are presented. Depending on
      the method of surgical treatment, patients with urinary stress incontinence have
      been divided into 3 groups: I group-(42 women), where retropubic colpo-uretero
      pexy has been performed following the rules previously suggested by Tanagho,
      Sprogis et al., with 92.8% of positive result, II group-(34 women), where
      Mieszczerski or Fothergill type of surgery has been performed, with 88.2% of
      positive results, and III group-(6 women), where vaginal vault has been suspended
      to the musculo-fascial flap, with positive results in all treated patients. The
      obtained results suggest that in every case of urinary stress incontinence the
      conservative approach should be the primary strategy of treatment. Analysis of
      the results revealed that retropubic colpo-uretero-pexy was an effective surgical
      method of urinary stress incontinence treatment in women with no cystocele and
      with proper uterine statics. In patients with correct uterine statics but with
      coexisting cystocoele, even of a minor grade, retropubical kolpouretropexy should
      be joined with the surgery from a vaginal access.

PMID- 7721160
TI  - [Prognostic survival of women after surgery for endometrial cancer].
AB  - The influence a few factors on prognosis on 5-th year survival has been estimated
      in 367 patients with endometrial cancer with stage I, II and III disease which
      underwent surgery and radiotherapy. The stage is the most important and competent
      authority indicators of prognosis on 5-th year survival, among prognostic
      variables for endometrial carcinoma the most important have been identified as:
      1) histologic type, 2) grading, 3) depth of myometrial invasion. The 5 year
      survival appeared correlated with the age of patients survival of patients
      younger than 59 years of age was higher and statistically significant.

PMID- 7721161
TI  - [Estrone concentration in endometrial cancer tissue in relation to body mass].
AB  - The estrone concentration was estimated in tissue of endometrial cancer and in
      the serum of 103 postmenopausal women. Patients were divided into two subgroups:
      normal body mass and overweight (above 130% of ideal body mass). The mean (+/-
      SED) tissue estrone concentration in women with normal body mass was 0.54 +/-
      0.06 pmol/g tissue and did not differ from that of overweight. Tissue estrone
      concentration correlated positively with Broc Index in subgroup with normal body
      mass and not in overweight.

PMID- 7721162
TI  - [Usefulness of determining tumor markers CEA, CA125 and CA72-4 in blood serum of
      patients with ovarian carcinoma].
AB  - Serum levels of 3 markers: CEA, CA125 and CA72-4 have been determined in 58
      patients aged from 15-60 years with histologically diagnosed ovarian cancer.
      Serum CEA was determined by radioimmunoassay using kits POLATOM (Poland), CA72-4
      was determined using kits CIS BIOINTERNATIONAL (France) and CA125 was determined
      by enzyme immunoassay using kits Hoffmann-la-Roche (Wien-Austria). We have
      observed the growth of sensitivity and specificity of serum levels: CA125 and
      CA72-4 if we have referred to the simultaneous elevation of CA125 and CA72-4
      markers. We have observed that CA125 and CA72-4 elevated levels were proceeded
      clinical recurrent of the disease from 2 to 6 months.

PMID- 7721163
TI  - [Evaluation of epithelial ovarian neoplasm immunologic reactivity using
      monoclonal antibodies].
AB  - The reactivity of five monoclonal antibodies against ovarian carcinoma-associated
      antigens (OC125, OV632, OV-TL3, 8C, 10B) on tissue sections of malignant and
      benign ovarian neoplasms was estimated and compared using PAP technique. The
      immunodiagnostic usefulness of OC125 and OV-TL3 antibodies in differentiation
      between serous and endometrioid ovarian carcinomas was indicated. OV632
      monoclonal antibody appears to be a good marker for differentiation between
      malignant and benign changes in ovary. Difficulties in typing of monoclonal
      antibodies for immunodiagnostic purposes were pointed out.

PMID- 7721164
TI  - [Use of aminoglutethimide in the hormonal treatment of patients with advanced
      breast cancer].
AB  - 54 patients (pts) with metastatic breast cancer were treated with
      aminoglutethimide 250 mg p.o. twice a day with hydrocortisone 40 mg p.o./day. All
      pts were postmenopausal, mean age 63 years, and pretreated with cytostatics
      and/or hormones. Dominant sites of metastases were: soft tissues 29 pts. bone 12
      pts. lungs 6 pts. Objective responses were: 4 (7.4%) CR, 15 (27.8%) PR, 16
      (29.6%) NC and 19 (35.2%) PD (UICC criteria). The response (CR + PR) at
      metastatic sites was: soft tissues 12 (41%), bone 4 (33%). The mean response
      duration was 15.0 months for CR; 10.2 for PR and 5.5 months for NC. The results
      of the study confirm that low--dose aminoglutethimide is an effective second-line
      hormonal treatment of advanced breast cancer.

PMID- 7721165
TI  - [Good clinical practice].
AB  - The main rules of the Good Clinical Practice were presented. The very important
      role of the informed consent, confidentiality and the investigator's moral
      responsibility was explained. The importance of the Ethical Committee was
      admitted.

PMID- 7721166
TI  - [Abdominal pregnancy at term with a live fetus].
AB  - The case of abdominal pregnancy at term with alive fetus, not recognized as
      abdominal pregnancy, was presented. It was diagnosed during elective cesarean
      section performed because of transverse fetus position and placenta praevia.

PMID- 7721167
TI  - [Laparoscopic ligature of the iliac arteries in treatment of hemorrhage related
      to uterine cervical cancer].
AB  - Laparoscopic ligation of internal iliac artery was performed in two patients with
      bleeding from stage II cervical cancer. The hemostatic effect, shortening of
      convalescence and early initiation of radiotherapy was obtained. Additionally,
      during procedure the laparoscopic lymph node sampling was performed. Laparoscopy
      appeared to be an alternative procedure to abdominal or extraperitoneal ligation
      of internal iliac artery.

PMID- 7721168
TI  - [Two cases of cancer developing from endometriosis in the minor pelvis 5 and 2.5
      years after hysterectomy and adnexectomy].
AB  - In two cases, 5 and 2.5 years after hysterectomy and bilateral adnexectomy
      (myomata uteri, bilateral endometrioid cysts and pelvic endometriosis)
      endometrioid carcinoma developed. Finding out the endometriosis during operation
      is an indication for precise removing of its residual and following careful
      examinations over the period of many years.

PMID- 7721169
TI  - [Male sterility caused by a lack of the acrosome in spermatozoa with a round
      shaped head].
AB  - Only properly structured spermatozoa are able for transportation and penetrating
      the permeable membrane of oocyte. The key role in the process of fertilization
      belongs to the anterior part of acrosome, i.e., the spermatozoon's head. A case
      of a married couple, with diagnosed 8-year-long infertility, has been presented.
      A spermocytogram, run in the man, revealed all spermatozoa to be with rounded
      heads, i.e., without acrosome. That pathology was confirmed in electron
      microscopy. The significance of correct examination--spermocytogram--has been
      stressed in the diagnostic of male infertility.

PMID- 7721170
TI  - [Goodpasture's syndrome as an autoimmune disease--identification of the
      autoantigen].

PMID- 7721171
TI  - [Conservative treatment of superficial transitional cell carcinoma of the
      bladder].

PMID- 7721172
TI  - [Preterm labor syndrome].

PMID- 7721173
TI  - [Thermal management of the newborn--a historical perspective].

PMID- 7721174
TI  - [Oils rich in omega-3 fatty acids--health implications].

PMID- 7721175
TI  - [Long-term stress residuals in former prisoners of the Yom Kippur War].
AB  - This study examines long-term adjustment following war captivity. 164 former
      prisoners-of-war (POWs) and 189 other combatants of the Yom Kippur War (1973)
      filled out a battery of questionnaires, assessing post-traumatic stress disorder
      (PTSD), trauma-related intrusive and avoidance tendencies, psychiatric
      symptomatology, and social functioning. Almost 2 decades after the war, 13% of
      former POWs suffer from diagnosed PTSD. Moreover, long-term residuals of war
      captivity are not limited to trauma-specific disorders. Former POWs reported more
      severe psychiatric symptomatology and more problems in functioning than the other
      combatants.

PMID- 7721176
TI  - [A psychiatrist's work with the homeless of Tel Aviv].
AB  - This is the first report of a psychiatrist's work (18 months) with the Tel Aviv
      homeless. A brief report of the phenomenon is given, as well as a few case
      descriptions. The work was performed under the patronage of the Tel Aviv
      Municipality. An attempt is made to provide the Israeli-Tel Aviv perspective from
      the legal, medical and psychiatric points of view.

PMID- 7721177
TI  - [Program for operating teams for quality improvement of hospital services].
AB  - In mid-1992, improvement of quality of service was set as a major goal in the
      framework of a 5-year plan at this hospital. This subject was selected in
      preparation for a new era in health care emerging in the world in general, and in
      Israel in particular. 6 problematic departments with high potential for
      improvement were chosen for the first stage of implementing a total quality
      management program (TQM). The goal was to gain experience through the
      implementation of TQM in a few medical and nonmedical departments in preparation
      for implementing TQM in the entire hospital. This process is ongoing and the
      first conclusions and perspectives are now being studied by all involved.

PMID- 7721178
TI  - [Timing of ultrasound examination in the detection of neonatal hydronephrosis].
AB  - The diagnosis of fetal hydronephrosis requires that there be ultrasound follow-up
      during the neonatal period. In most cases the dilatation of the renal collecting
      system regresses and no further diagnostic work-up is needed. A persistently
      dilated collecting system might be the result of obstruction, in which case
      surgical intervention should be considered. The ultrasound examination is the key
      factor in deciding whether to proceed with invasive procedures (cystography,
      intravenous pyelography or renal isotopic scan) or to stop urological
      investigation. The case presented emphasizes the importance of the timing of the
      first ultrasonographic study after birth. Ultrasound examination performed within
      the first 48 hours can lead to false negative results.

PMID- 7721179
TI  - [Ocular onchocerciasis in Israel].
AB  - Onchocerciasis is a systemic disease caused by the filarial parasite Onchocerca
      volvulus. It is endemic in Central Africa and South America and causes blindness
      which is directly related to the severity of the infection. World-wide, there are
      about 18 million suffering from onchocerciasis, of whom 2 million are blind. The
      most common symptom is pruritus, which appears early in the disease. Ocular
      manifestations appear later, and when present, life expectancy is less than 10
      years. We present a 31-year-old male Ethiopian immigrant with this disease, which
      was brought to Israel with the Ethiopian immigration of the past decade. In this
      population can be found the various manifestations of the disease in all its
      stages. Patients are treated with oral Ivermectin, once a year, the safest of
      known medications for this disease. The need for early detection and treatment is
      emphasized because of the potential for ocular destruction.

PMID- 7721180
TI  - [Schistosomiasis imported from Africa].
AB  - We present 5 cases of Schistosoma hematobium infestation recently acquired during
      travel to Lake Malawi. Clinical presentations ranged from asymptomatic to
      prolonged pneumonitis. The laboratory diagnosis in suspected cases rests on both
      searching for ova in the urine, and on serological tests which may become
      positive before the appearance of ova. One of the returning travelers also
      acquired trichinosis and another amebiasis. Because of the sharp increase in
      those traveling to the tropics, especially young people, physicians should be
      aware of the possibilities of their acquiring schistosomiasis.

PMID- 7721181
TI  - [Transient thyroid dysfunction during chronic viral hepatitis treated with alpha
      interferon].
AB  - 2 patients with chronic viral hepatitis were treated with alpha-interferon and
      developed thyroid dysfunction. Both patients were previously euthyroid and had
      thyroids of normal size. 1 developed hypothyroidism (FT4 0.49 micrograms/dl; TSH
      26.8 mIU/ml) and the other developed hyperthyroidism (FT4 2.72 micrograms/dl; T3
      366 ng/ml; TSH 0.15 mIU/ml) 4 and 6 months, respectively, after commencing
      interferon. Interferon was discontinued, and thyroid function tests returned to
      normal within 1 and 2 months, respectively, and have remained normal for over a
      year. Antimicrosomal antibodies in the hypothyroid patient were positive
      (1:6400), but became negative after 4 months. No specific therapy for the thyroid
      disorders was given. These findings suggest that alpha-interferon induced
      transient thyroid dysfunction in patients who were previously euthyroid and were
      negative for thyroid autoantibodies.

PMID- 7721182
TI  - [Retroperitoneal perforation after endoscopic sphincterotomy: the dilemma of
      management].
AB  - Retroperitoneal perforation is an occasional complication of endoscopic
      retrograde cholangiopancreatography, which is expected to increase in frequency.
      The outlook for patients with this complication is good. Conservative,
      nonsurgical management is suitable for most patients. The main goal is to achieve
      adequate drainage of the common bile duct which can be done endoscopically.
      Despite persistent obstruction an initial period of conservative management is
      usually appropriate. Surgical intervention should be withheld until the patient's
      condition is becoming worse, or until a complication such as localized
      retroperitoneal abscess is recognized.

PMID- 7721183
TI  - [Testicular metastasis from transitional cell carcinoma of the bladder].
AB  - We present a 54-year-old man with a testicular metastasis originating from a
      transitional cell carcinoma of the urinary bladder. Initially, radical cystectomy
      and ileal-conduit urinary diversion were performed, followed 9 months later by
      urethrectomy for local recurrence. A year later he presented with a tumorous
      right testis proved to harbor transitional cell carcinoma.

PMID- 7721184
TI  - [Acute renal failure with hepatic involvement after methylene chloride
      inhalation].
AB  - A 29-year-old man working in a closed room was exposed to methylene chloride. 2
      days later he developed acute renal failure and hepato-cellular damage. Despite
      the fact that methylene chloride is usually considered nontoxic, fatal cases have
      been described. It should be stressed that a good history, especially in those
      who work with materials of low toxicity, can explain complex clinical pictures,
      allowing proper treatment to be started. Our patient was treated by hemodialysis
      and recovered completely without residual hepatic damage.

PMID- 7721185
TI  - [Molecular genetic diagnosis of familial dysautonomia].

PMID- 7721186
TI  - [The health system copes with the problem of aging].

PMID- 7721187
TI  - [Localization of the familial dysautonomia gene to chromosome 9q31-33 and the
      development of a genetic test for the disease].

PMID- 7721188
TI  - [Neuronal cell death and intracellular proteinase functions].
AB  - Recently, attention has been paid to intracellular proteinase functions in
      relation to the process of neuronal cell death, and defining how they are
      involved is essential for developing neuroprotective strategies as well as for
      understanding the pathology of neurodegenerative diseases. Several recent
      articles have outlined the activation and deleterious effect of mu-calpain, a
      calcium-activated cysteine proteinase, on the cytoskeleton protein network, which
      is thought to lead to cell death. Furthermore, a marked increase in cathepsins B,
      L, and D, lysosomal proteinases, and cathepsin E, non-lysosomal aspartic
      proteinase, in neurons has been shown in the early stage of neuronal
      degeneration. The increased levels of these lysosomal cathepsins in degenerating
      neurons are considered to be associated with stimulated autophagy, which
      occasionally can lead to neuronal cell death. The molecular form of cathepsin E
      accumulated in affected neurons was different from that of the normal cathepsin E
      molecule. This unusual molecular form of cathepsin E is likely to be critical for
      disruption of normal cellular function, possibly culminating in neuronal cell
      death. The increased level of such proteinases was also found in reactive glial
      cells. In these cells, cathepsin E was increased as a mature form exclusively in
      reactive microglial cells, while cathepsins D and G were increased mainly in
      reactive astrocytes. Overproduction of cathepsins E, D and G in these reactive
      glial cells may be finally involved in the pathogenesis of neuro-degenerative
      disease.

PMID- 7721189
TI  - [Pharmacological studies on receptive mechanisms for N-methyl-D-aspartic acid
      signals].
AB  - A series of investigations has been made to analyze the receptive mechanisms for
      signals mediated by an N-methyl-D-aspartic acid (NMDA)-sensitive subclass of
      brain excitatory amino acid receptors. Treatment of synaptic membranes with a low
      concentration of Triton X-100 induced a drastic disclosure of NMDA-sensitive
      [3H]glutamic acid binding without affecting the NMDA-insensitive populations. In
      these Triton-treated membranes, binding of [3H]glycine (Gly) was displaced by D
      serine and D-alanine, but not by strychnine. These membrane preparations were
      also useful for detecting the binding of noncompetitive blockers to open NMDA
      channels in a manner highly sensitive to potentiation by NMDA, Gly and the
      polyamine spermidine. Comparative studies on the binding of agonist and
      antagonist ligands in different central regions suggested the possible
      heterogeneity of the NMDA, Gly and ionophore domains. By screening more than 1000
      compounds, the binding of noncompetitive blockers was completely abolished by the
      addition of 6,7-dichloroquinoxaline-2,3-dione, which was revealed to be a
      selective antagonist for the Gly domain. Binding studies using the aforementioned
      radioligands gave rise to the idea that both reduced and oxidized glutathione
      could be endogenous agonists for the NMDA domain. An i.c.v. injection of NMDA led
      to a marked potentiation of DNA binding activities of particular transcription
      factors in a manner sensitive to antagonism by antagonists at the respective
      domains. These results suggest that NMDA signals are indeed transduced from cell
      surfaces into nuclei to express nuclear transcription factors through the NMDA
      sensitive subclass that is a receptor ionophore complex consisting of at least 4
      different constituents including the NMDA, Gly, polyamine and ionophore domains.

PMID- 7721190
TI  - [Differential involvement of PKC subspecies in neuronal function].
AB  - Protein kinase C (PKC) is a key enzyme involved in various types of signal
      transduction, and it is most abundant in the nervous system. Available evidence
      suggests that PKC plays a prominent role in neuronal transmission. PKC is a
      member of a family consisting of at least eleven subspecies: alpha, beta I, beta
      II, gamma, delta, epsilon, eta, theta, mu, zeta and lambda. The individual role
      of each subspecies could not be demonstrated because of the homologous structure
      of the PKC subspecies. We studied the distinct functional roles of PKC subspecies
      in the central nervous system by defining the detailed localization of each
      subspecies. The immunocytochemical localization suggested that cPKCs (alpha, beta
      I, beta II, and gamma) function postsynaptically, while epsilon-PKC
      preferentially modulates the synaptic efficacy in the presynapse. GAP-43, a
      presynaptic PKC substrate involved in neuronal plasticity, was preferentially
      phosphorylated by epsilon-PKC rather than alpha, beta and gamma-PKC. As the
      epsilon-PKC could be activated by arachidonic acid, it is strongly suggested that
      in the case of LTP, the presynaptic epsilon-PKC is activated by arachidonic acid
      released postsynaptically and phosphorylates GAP-43, resulting in the increase in
      glutamate release.

PMID- 7721191
TI  - [Stimulation of insulin release and cAMP levels in isolated rat islets by the
      imidazoline alpha 2-adrenoceptor antagonist midaglizole: comparison with the
      action of the alpha 2-adrenoceptor antagonist yohimbine].
AB  - Midaglizole, an imidazoline derivative, is a highly selective alpha 2
      adrenoceptor antagonist structurally different from the classical alpha 2
      antagonist yohimbine. We compared the effects of midaglizole and yohimbine on
      insulin release and cAMP levels in isolated rat pancreatic islets to clarify the
      mechanisms underlying the hypoglycemic action of midaglizole. Midaglizole
      reversed epinephrine-induced inhibition of insulin release and reduction of cAMP
      levels, as did yohimbine. This agent, however, enhanced both insulin release and
      cAMP levels stimulated by glucose in the absence of epinephrine, unlike
      yohimbine. Moreover, the enhancing effects of midaglizole still remained, even if
      the action of alpha 2-adrenoceptors in the islets was blocked by pre-treatment
      with islet-activating protein (IAP) or by exposure to yohimbine. Under the same
      conditions, these effects were completely abolished by the Ca-channel blocker
      verapamil. The above results demonstrate that midaglizole may stimulate insulin
      release by the dual actions of alpha 2-adrenoceptor blockade and direct
      stimulation of pancreatic cAMP production.

PMID- 7721192
TI  - [Study on the experimental ulcerative colitis (UC) model induced by dextran
      sulfate sodium (DSS) in rats (2)].
AB  - We have confirmed that symptoms in the experimental UC model in rats induced by
      ingesting 3% DSS were similar to those of the human UC. In this study, we
      investigated the procedure for assessing the therapeutic effect of SASP and PSL.
      (1) The UC model was produced by giving rats drinking water containing 3% DSS,
      and animals were selected when bloody stool was observed in more than 90% of the
      animals. (2) Procedure for selection of rats: (a) presence of bloody stool for
      more than two consecutive days, (b) concentration of hemoglobin at more than 10
      g/dl and (c) B.W. on the day of selection was not decreased more than 20 g
      against the B.W. on the day before the selection. (3) After selection, various
      concentrations of DSS (1-3%) were given to rats for 14 days. SASP and PSL were
      administered to the UC model once a day for 14 and 7 days, respectively, with the
      animals given drinking water containing 1% DSS after the selection. SASP (100
      mg/kg, p.o.) and PSL (1 mg/kg, i.r.) significantly inhibited the formation of
      erosion by 56.1 and 47.5%, respectively. In conclusion, this procedure used
      herein seems to be useful for assessing the therapeutic effect of a drug for
      human UC.

PMID- 7721193
TI  - [Therapeutic effect of IGN-2098, a new antiulcer drug (H2-antagonist), in the
      ulcer diminishing period against acetic acid-induced gastric ulcer in rats].
AB  - The effects of IGN-2098 on the healing process of acetic acid-induced gastric
      ulcer was investigated in comparison with the other histamine H2-receptor
      antagonists, famotidine and roxatidine acetate HCl, in rats. Ulcer was induced by
      the injection of acetic acid solution (20%, 0.05 ml). From the 4th day to 17th
      day after the ulcer induction, drugs were orally administered twice a day. On the
      18th day after the ulcer induction, rats were sacrificed to measure the ulcer
      index macroscopically and to take pictures of the stomachs. Judging from the
      photographs, the prominence of ulcer the edge was graded into 4 classes, which
      showed a significant correlation with the histological amount of connective
      tissue at the ulcer edge. All drugs accelerated the healing of the ulcer, and the
      effect of IGN-2098 was the most remarkable. In addition, IGN-2098-treatment
      exhibited more marked inhibition against the prominence of the ulcer edge as
      compared with the control group. Based on these results, it is concluded that IGN
      2098 may be a useful drug for the clinical treatment of ulcer and that the
      healing acceleration by IGN-2098 without prominence of the ulcer edge may induce
      no relapse of the ulcer after healing.

PMID- 7721194
TI  - [The protective effect of benidipine hydrochloride against hypoxic myocardial
      injury of cultured mouse fetal heart cells].
AB  - The protective effect of benidipine hydrochloride, a 1,4-dihydropyridine calcium
      antagonist, was investigated in cultured mouse fetal heart cells under the
      hypoxic condition (PO2, < or = 20 mmHg). The preparation of cultured fetal mouse
      heart muscle cells was subjected to the hypoxic condition for 24 hr. After the
      hypoxic treatment for 24 hr, the spontaneously beating rate of cultured heart
      cells was reduced subsequently and the beating almost ceased. Protection against
      cell injury was assessed by cell viability (NR assay), LDH release and cellular
      ATP levels. Under the hypoxic condition, cell viability and cellular ATP levels
      were markedly decreased, and LDH release was increased. Benidipine hydrochloride,
      at concentrations higher than 1-10 nM, strongly protected against the decreases
      in cell viability and cellular ATP levels as well as the increase in LDH release.
      The potency of the protective effect of benidipine hydrochloride was greater than
      those of the other tested 1,4-dihydropyridine calcium antagonists (nisoldipine,
      nitrendipine and nifedipine). These results suggest that benidipine hydrochloride
      exerts protective actions against hypoxic myocardial injury of cultured mouse
      fetal heart cells.

PMID- 7721195
TI  - [Inhibition of induced contraction in the isolated rat mesenteric vascular bed by
      Ro 40-5967, a novel calcium antagonist].
AB  - We designed a study to investigate the effect of the non-dihydropyridine calcium
      antagonist Ro 40-5967 in the isolated rat mesenteric vascular bed and compared it
      with that of nifedipine. Ro 40-5967 (10(-6) M) suppressed the KCl-induced
      contractions, with a potency similar to that of nifedipine (10(-7) M). A bolus
      injection of norepinephrine and a periarterial nerve stimulation associated with
      the mesenteric artery increased the perfusion pressure. Ro 40-5967 (10(-6) M)
      significantly inhibited the contractions induced by norepinephrine and the
      contractions of the stimulated periarterial nerve in the rat mesenteric arterial
      bed. In contrast, nifedipine (10(-7) M) did not affect these contractile
      responses. A subthreshold concentration of endothelin-1 potentiated the
      contractile responses to norepinephrine and the periarterial nerve stimulation.
      Ro 40-5967 (10(-6) M) prevented the potentiation of the responses to
      norepinephrine and the periarterial nerve stimulation evoked by endothelin-1,
      whereas nifedipine (10(-7) M) did not affect this augmentation. Compared to the
      effects of nifedipine (10(-7) M), we conclude that Ro 40-5967 (10(-6) M) more
      effectively prevents the contractions induced by norepinephrine and stimulation
      of the periarterial nerve and furthermore prevents the amplification of these
      contractions by endothelin-1. Ro 40-5967 does not seem to block the L-type
      calcium channel and exerts its effect via some other mechanism.

PMID- 7721196
TI  - Morphometrics and growth in captive aye-ayes (Daubentonia madagascariensis).

PMID- 7721197
TI  - Dietary intake, food composition and nutrient intake in wild and captive
      populations of Daubentonia madagascariensis.
AB  - Data are presented on dietary and nutrient intake in a wild population of aye
      ayes. Study animals ate 4 main food types: seeds, nectar, fungus and insect
      larvae. Calculated calorie intake was slightly lower during the cold season than
      during the hot, wet and the hot, dry seasons. Total intakes almost doubled to
      compensate for the lower energy content of the diet during the cold season.
      Comparison of natural and captive diets suggests that maintenance and even growth
      requirements of aye-ayes can be met by relatively low-fat, low-protein diets.
      Daily energy requirements were estimated to average about 280 kcal metabolizable
      energy/day. Animals in the wild were estimated to eat between 260 and 342 kcal,
      while captive animals consumed 260 kcal/day.

PMID- 7721198
TI  - Tap-scanning and extractive foraging in aye-ayes, Daubentonia madagascariensis.
AB  - The trees on which aye-ayes forage contain complex communities of organisms. Aye
      ayes appear to use tap-scanning behaviour, in combination with complex perceptual
      and inferential capabilities, to exploit these communities as a source of food.
      In doing so, they alter them, perhaps to their own advantage.

PMID- 7721199
TI  - Preliminary observations on hand preference for tapping, digit-feeding and food
      holding in captive aye-ayes (Daubentonia madagascariensis).
AB  - Aye-ayes possess highly adapted hands, using their specialized third digits to
      investigate potential food sources by tapping and the third or fourth digits to
      transfer food to the mouth. Observations were conducted on 11 captive aye-ayes
      (10 wild-caught; 1 captive-bred) following presentation of food or novel objects,
      and hand use for holding, tapping and digit-feeding was scored. Eight of the
      individuals showed significant hand preferences for one or more of the 3
      measures, although there was no consistent pattern. These preliminary results are
      compared to those from other lemur species.

PMID- 7721200
TI  - The giant aye-aye Daubentonia robusta.
AB  - Subfossils of a giant form of aye-aye are found at scattered sites in the south
      and southwest of the island of Madagascar, outside the known distribution of the
      living, or common, aye-aye. The subfossil aye-aye, named Daubentonia robusta, has
      massive, robust limb bones implying a species with a body weight 2.5-5 times as
      great as that of the living species. A mystery exists regarding how a species
      this large with the same specializations of teeth and manus as the living species
      could have existed in a xeric environment.

PMID- 7721201
TI  - Aye-ayes: specialists on structurally defended resources.
AB  - During the course of a 2-year field study on aye-ayes (Daubentonia
      madagascariensis), data were collected on dietary composition, food acquisition
      and structural properties of food resources. Aye-ayes in this study sampled
      remarkably few species from a variety of food types. A majority of these
      resources were heavily structurally defended and therefore difficult of access
      for other mammals. Aye-ayes used their modified finger and anterior teeth to
      harvest most of these resources.

PMID- 7721202
TI  - Positional behaviour in captive aye-ayes (Daubentonia madagascariensis).
AB  - The aye-aye shows numerous special features in its postcranial skeleton, partly
      in association with its unusual feeding habits and partly in association with
      locomotor specialisation connected with the possession of claws. This study
      examined the positional behaviour of 3 captive adult aye-ayes in order to throw
      light on these morphological specialisations. Locomotion was dominated by
      quadrupedal walking and climbing. Given the relatively large body size of aye
      ayes, an unexpectedly high frequency of head-first descent was observed. This may
      provide an explanation for two characteristics of aye-ayes: robusticity of the
      shoulder girdle and high compressive and bending strengths of the humerus. Agile
      leaping was also observed, contrasting with previous reports that this species is
      characterised by slow, cautious movement. Specific morphological features that
      are shared with slow-moving lorisids may be attributable to a combination of
      frequent head-first descent and postural suspension.

PMID- 7721203
TI  - Vocalizations of aye-ayes (Daubentonia madagascariensis) in captivity.

PMID- 7721204
TI  - Responses of captive aye-ayes (Daubentonia madagascariensis) to the scent of
      conspecifics: a preliminary investigation.
AB  - The ability of 6 captive aye-ayes (Daubentonia madagascariensis) to discriminate
      scents from conspecifics of different age-sex classes was tested. The animals
      were presented with either unscented logs or logs that had been placed in: (1)
      their own cage, (2) the cages of adult males or (3) the cages of adult females
      with female offspring. Responses to the logs, measured by approaching, proximity,
      tapping, gnawing, sniffing, scent marking and vocalizations, were recorded for 30
      min following presentation. Logs from females with offspring provoked the highest
      responses, and immature aye-ayes investigated logs more than adults of either
      sex. These results suggest that, as in many other prosimians, olfaction plays an
      important role in the communication systems of aye-ayes.

PMID- 7721205
TI  - Haematology and serum biochemistry values in aye-ayes (Daubentonia
      madagascariensis) at the Duke University Primate Center.

PMID- 7721206
TI  - Field observations of aye-ayes (Daubentonia madagascariensis) in Madagascar.
AB  - Data are presented from a field study of aye-ayes (Daubentonia madagascariensis)
      in an area of degraded secondary forest in northeast Madagascar. Animals were
      followed by radiotelemetry for 3 months during the cool dry season, when
      productivity of the forest is at a minimum. Population density was variable. Male
      home ranges were larger and overlapped the range of at least 1 female. Male
      ranges also overlapped, and areas of overlap could be occupied by 2 animals
      simultaneously. Most of the parties were solitary, but aggregations were observed
      at feeding sites. All activity was observed during darkness, and aye-ayes were
      always found to nest singly during the daytime. These patterns conform to those
      described for other nocturnal solitary prosimians. The aye-ayes showed
      versatility in their locomotor patterns, enabling them to use all types of
      supports and forest levels. Dietary diversity was high, although a preference for
      flower nectar was noted. These results suggest that, despite their anatomical
      specializations, aye-ayes are able to exploit a wide range of resources within
      recently degraded forest. This ability seems to allow aye-ayes to remain active
      throughout the year, unlike certain other nocturnal lemurs which become torpid
      during the dry season.

PMID- 7721207
TI  - Ecoethological study of free-ranging aye-ayes (Daubentonia madagascariensis) in
      Madagascar.
AB  - An ecoethological study was undertaken on the activity rhythms, diet, ranging and
      social behavior of 3 aye-ayes. Preliminary information on reproduction and mother
      infant relations are given. The study included research into the different
      habitat types in which the aye-aye was found within the Biosphere Reserve at
      Mananara-Nord. In addition, the impact of habitat degradation on aye-aye ecology
      was investigated. The aye-ayes spent the majority of time in locomotion; resting
      accounted for a surprisingly small amount of their activity cycles. Animals spent
      almost half of their time between 0 and 10 m above ground. Signs of aye-aye
      activity were never found in highly disturbed areas but were common in
      plantations, secondary littoral and primary forests.

PMID- 7721208
TI  - Evidence for nonseasonal reproduction in wild aye-ayes (Daubentonia
      madagascariensis).
AB  - The lemurs of Madagascar typically exhibit a strictly seasonal pattern of
      breeding, with a limited number of successive estrous cycles occurring at a
      particular time of the year, which varies from species to species. Previous
      reports indicated that aye-ayes also exhibit such a strictly seasonal polyestrous
      pattern. Data from the author's 2-year field study of aye-ayes on the island of
      Nosy Mangabe, combined with information from recently initiated captive breeding
      programs, now indicate that this species in fact shows an extended breeding
      season or even year-round breeding. Actual mating or signs of estrus were
      observed in the field throughout a 5-month period (October-February). Further,
      data from captured pregnant females and young offspring indicate that births take
      place during the period from February to September. Apart from aye-ayes, extended
      breeding periods have been reported for wild Eulemur coronatus and for captive
      Eulemur fulvus and Mirza coquereli. Analysis of information on seasonal variation
      in food availability for aye-ayes and other lemurs provides no clear evidence
      that the degree of seasonality of breeding is directly dependent on ecological
      factors.

PMID- 7721210
TI  - Aye-ayes: out of the dark and into the light?

PMID- 7721209
TI  - Maintenance and breeding of aye-ayes (Daubentonia madagascariensis) in captivity:
      a review.
AB  - The husbandry practices of the 3 institutions currently holding captive aye-ayes
      outside Madagascar (Jersey Wildlife Preservation Trust, Duke University Primate
      Center and Paris Zoo) are reviewed. Information on housing, diet, oestrous cycles
      and infant rearing is included. Aye-ayes are active, nocturnal animals that are
      mainly solitary in the wild. They need large cages that are well furnished with
      arboreal substrates. Captive diet consists of fruit, nuts, insects and a pellet-
      or cereal-based gruel. Breeding of aye-ayes occurs either within stable pairs of
      animals or in pairs that are mixed only during the peri-ovulatory period.

PMID- 7721211
TI  - Preliminary study of the sexual behaviour of three aye-ayes (Daubentonia
      madagascariensis) in captivity.
AB  - This paper deals with the process of mating among captive aye-ayes (Daubentonia
      madagascariensis). Data on sexual behaviour of 3 wild-caught aye-ayes were
      collected over a period of 3 years (1986-1989). The group of 2 adult females and
      a young male was housed at the Vincennes Zoo, Paris. The seasonal poly-oestrous
      sexual cycle was found to be marked by four clear phases of the females' vulval
      tumescence and coincided with sexual interest shown by both sexes. The external
      genitalia of the females are described, as are marking behaviour and sexual
      behaviour patterns before, during and after copulation. The behaviour and sexual
      cycles of these 2 females were compared with records from other lemurs.

PMID- 7721212
TI  - Infant development in a captive-bred aye-aye (Daubentonia madagascariensis) over
      the first year of life.
AB  - An adult wild-caught female aye-aye (Daubentonia madagascariensis) and her
      captive-bred offspring were studied for 2 weeks pre partum and 52 weeks post
      partum. Data on activity, substrate use, approach-leave interactions and social
      interactions were recorded in 30-min samples. Observations on the mother were
      started 10 days pre partum, and 2 h of data were collected on each of 9 days up
      to birth. Observations in each week were split evenly over 5 days and between two
      4-hour blocks of time during the aye-ayes' active (dark) period. Ten h of data
      were collected in weeks 1-24, 5 h in weeks 25-40 and 2.5 h in weeks 40-52. Infant
      development and patterns of interaction with the mother, in terms of
      responsibility for proximity, grooming, play and food-sharing behaviour are
      described. Comparison with other prosimians indicates that aye-aye infants
      develop relatively slowly. The infant aye-aye first emerged from the nestbox in
      week 8, tried solid food in week 14, but did not feed herself regularly until
      week 20, and was still food begging and attempting to suckle at a year of age.
      This long period of dependence is inferred to be related to the aye-aye's unique
      percussive and extractive foraging techniques, which require fine motor
      coordination and skill, and which take time and practice to develop proficiency.

PMID- 7721213
TI  - Taxonomy and distribution of Daubentonia: a historical perspective.

PMID- 7721214
TI  - Development of behaviour in a young aye-aye (Daubentonia madagascariensis) in
      captivity.
AB  - This paper provides descriptive and quantitative information on the development
      of a young aye-aye in captivity during its first 10 months of life. The mother's
      behaviour was observed to provide an adult standard against which to evaluate the
      young male's development. Early development of the young aye-aye (including early
      vocalizations, locomotion and manipulation, acquisition of independence from the
      mother, threat/defence and alarm) is described in qualitative terms. Quantitative
      data on a number of other behaviours were collected using focal-animal sampling.
      Overall, this study indicated that the young aye-aye is relatively poorly
      developed during the 2-month nest phase but shows rapid development in comparison
      to other primates once it has left the nest.

PMID- 7721215
TI  - [Why are complementary treatment measures so popular?].

PMID- 7721216
TI  - [Should complementary medicine be scientifically evaluated?].

PMID- 7721217
TI  - [Proving the effectiveness of complementary therapy. Analysis of the literature
      exemplified by acupuncture].
AB  - At present, acupuncture may be considered one of the most popular forms of
      complementary medicine worldwide. However, in relation to the number of reviews
      on the subject, comparatively few controlled clinical trials have been reported
      so far. An analysis of all the controlled clinical trials listed in MEDLINE
      between 1987 and March 1994 (n = 39) that met certain basic requirements revealed
      that they addressed a wide variety of diseases and/or symptoms with no major
      focus (apart from the symptom of pain, which of course is highly complex in
      nature). In agreement with the findings of other meta-analyses, most of the more
      recent papers have been found to be still of indifferent quality. Besides the
      inherent problem that the term acupuncture subsumes within itself a substantial
      number of different techniques (and even philosophies), an obvious methodological
      deficit can be observed. Many groups seem to attach too little importance to
      choosing an appropriate control model, although seminal papers addressing this
      problem were already published in the early eighties. Similar remarks apply to
      inadequacies in study design, which should be at least single-blind. In summary,
      these findings may well help to explain why the effectiveness of acupuncture has
      still not been definitively demonstrated.

PMID- 7721218
TI  - [Arterial occlusive disease--periodic hemodynamics and skin oxygenation].

PMID- 7721219
TI  - [The heart as an endocrine organ. Regulation and liberation of atrial natriuretic
      peptides ANP and BNP].

PMID- 7721220
TI  - [Differential diagnosis of hepatitis A, B, C, D and E. Clinical, biochemical and
      viral serologic criteria. 6: Hepatitis E serology].

PMID- 7721221
TI  - [Amlodipine in long-term treatment of mild and moderate hypertension. A
      multicenter study].
AB  - METHOD: An open, multicenter study was conducted to investigate the
      antihypertensive efficacy and safety of amlodipine in the long-term treatment of
      patients with mild to moderate essential hypertension of a period of 178 weeks
      (3.4 years). RESULTS: 92 of the 110 patients participating in the study received
      amlodipine treatment throughout the total study period, with 77 patients on
      amlodipine monotherapy (mean daily dose 6.3 mg), and 15 patients on combination
      antihypertensive therapy including amlodipine (mean daily dose 7.1 mg). After 8
      weeks of treatment the diastolic target blood pressure of < or = 90 mmHg was
      achieved in 86 out of 92 patients (93.5%). The mean diastolic blood pressure
      reduction was retained throughout the treatment, both in patients receiving
      monotherapy and those on combination therapy. The incidence of adverse events was
      highest during the first 12 weeks of treatment (30.0%); after another 54 weeks it
      dropped to 18.1%, and to 7.3% during the last 112 weeks. The side effects
      reported most frequently were headaches and edema. CONCLUSION: These results
      indicate that amlodipine effects sustained reduction in diastolic blood pressure
      over a period of more than 3 years in patients with mild to moderate
      hypertension.

PMID- 7721222
TI  - [Combatting nosocomial intestinal infections with yeasts].

PMID- 7721223
TI  - [Immune system under stress: travel and immune reactivity].

PMID- 7721224
TI  - [Stress and immune response--the psychoneuroimmunologic network. Interactions
      between the CNS and immune system].

PMID- 7721225
TI  - [Acute therapy of tachycardic arrhythmias. 1: Anti-arrhythmia agents,
      supraventricular tachycardia].

PMID- 7721226
TI  - Clinical application of mefloquine pharmacokinetics in the treatment of P
      falciparum malaria.
AB  - Malaria remains a major public health problem in large areas of the world. One of
      the major factors responsible for the resurgence is the emergence of Plasmodium
      falciparum, resistant to available antimalarials. An antimalarial, mefloquine,
      has been considered since its introduction as a promising alternative
      antimalarial drug to overcome the situation of widespread multidrug resistant P
      falciparum. Pharmacokinetic studies of mefloquine have been investigated in
      several groups of subjects either as mefloquine alone or as combined regimens.
      The oral absorption of mefloquine is relatively rapid, reaching peak
      concentrations within 24 hours. Metabolism takes place in the liver, with
      carboxymefloquine as a major metabolite. Mefloquine has a large apparent volume
      of distribution of 200 L and is highly bound (98%) to plasma proteins. The
      elimination is slow; the terminal half-life is 13 10 to 14 days in Thai patients
      with falciparum malaria. Vomiting within 1 hour of drug administration has an
      influence on blood concentrations of mefloquine and this may result in treatment
      failure. The whole blood concentrations of mefloquine on the first two days of
      treatment are important determinants of parasitological response. There appear to
      be no pharmacokinetic interactions between mefloquine and the other two
      components of Fansimef in patients with uncomplicated falciparum malaria. The
      advantage of this combination over mefloquine alone in multidrug resistant P
      falciparum is still debatable. However, recent data seem to support the higher
      efficacy of Fansimef over mefloquine alone. Concurrent administration of
      antibiotics, ie ampicillin and tetracycline with mefloquine results in a
      significant increase in maximum concentration, reduction of the apparent volume
      of distribution and shortening of the terminal elimination half-life of
      mefloquine. An antiemetic drug metoclopramide accelerates the absorption of
      mefloquine and increases the maximum concentration. In contrast, mefloquine
      concentrations are decreased in the presence of an antimalarial, artesunate.
      Primaquine has no effect on the pharmacokinetics of mefloquine when given
      concurrently.

PMID- 7721227
TI  - Positron emission tomography and central neurotransmitter systems in movement
      disorders.
AB  - This article discusses the anatomical and neurochemical structure of the basal
      ganglia and reviews the Positron Emission Tomographic (PET) ligands available for
      investigating these pathways. We discuss how clinical PET studies have improved
      our understanding of the neurochemical changes underlying principal movement
      disorders.

PMID- 7721228
TI  - Protective role of glutathione on alpha 1 proteinase inhibitor inactivation by
      the myeloperoxidase system. Hypothetic study for therapeutic strategy in the
      management of smokers' emphysema.
AB  - In smoking subjects with obvious emphysema, the interaction between neutrophil
      derived MPO and H2O2 produced by alveolar inflammatory cells (alveolar
      macrophages (AM) and polymorphonuclear neutrophils (PMN)) has the ability to
      spontaneously inactivate, in vitro, the alpha 1 proteinase inhibitor (alpha 1PI).
      This inactivation can induce a desequilibrium of the protease-antiprotease
      balance in the lungs. In this study, we investigated the ability of glutathione
      to protect alpha 1PI. In a cellular model of alpha 1PI inactivation mimicking the
      effects of alveolar inflammatory cells present in the lower respiratory tract of
      smoking patients with emphysema, we demonstrated that glutathione can protect
      alpha 1PI against the oxidative inactivation by these activated cells. This
      protection has been computed in a cellular experimentation (AM and MPO-system)
      with a 50% inhibitory concentration of 62 microM. Moreover, glutathione has an
      important inhibitory effect directly on H2O2 released by PMA-stimulated AM (IC50
      = 30 microM) or PMA stimulated PMN (IC50 = 70 microM). The mechanism, which
      governs glutathione may be a result of a scavenging effect on H2O2 as
      demonstrated in a free cellular experiment. With this in vitro demonstrated
      effectiveness, glutathione as a therapeutic antioxidant, via the aerosol, has
      been proposed, in order to prevent tissue damage, inflicted by an excess of
      activated phagocytic cells, in some lung diseases such as smoking patients with
      emphysema.

PMID- 7721229
TI  - Mice plasma and brain pharmacokinetics of amitriptyline and its demethylated and
      hydroxylated metabolites after half-life repeated administration. Comparison with
      acute administration.
AB  - Kinetics of amitriptyline (AMI), its demethylated metabolites nortriptyline (NOR)
      and demethylnortriptyline (DM-NOR), and its hydroxylated metabolites, the E and Z
      isomers or 10-hydroxy-amitriptyline (E- and Z-10-OH-AMI) and of 10
      hydroxynortriptyline (E- and Z-10-OH-NOR) were studied in plasma and brain from
      Swiss CD1 mice after six successive intraperitoneal injections of amitriptyline
      (10 mg/kg) administered every elimination half-life time (t1/2 = 3.1 h) to obtain
      the steady state. In these conditions, AMI was metabolised rapidly. Compared with
      acute administration, hydroxylation reactions were saturated by the repeated AMI
      injections and demethylation became preponderant both in plasma and brain. Thus,
      plasma levels of demethylated metabolites, NOR and DM-NOR, increased (49% and 13%
      of total AUC against 22% and 7% in acute conditions, respectively), while levels
      of AMI and its hydroxylated metabolites, 10-OH-AMI and 10-OH-NOR, decreased (8%,
      2.5% and 27.5% against 17%, 8% and 46% in acute conditions, respectively).
      Likewise in brain tissue, when AMI was repeatedly administered, NOR and DM-NOR
      increased (62% and 22% against 29% and 11%, respectively) while AMI and 10-OH-AMI
      decreased (11.5% and 1% against 47% and 9%, respectively). These differences may
      account for modified pharmacological effects seen after half-life repeated
      administration of AMI since demethylated metabolites exert a more marked
      inhibiting effect than AMI on noradrenaline reuptake.

PMID- 7721230
TI  - Intracoronary infusion of bradykinin: effects on noradrenaline overflow following
      reperfusion of ischemic myocardium in the anesthetized dog.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of intracoronary
      bradykinin (BK) infusion on noradrenaline release and ventricular arrhythmias
      induced by coronary occlusion and reperfusion in the anesthetized dog. METHODS:
      14 anesthetized adult mongrel dogs of either sex underwent a 60 min occlusion of
      the left anterior descending coronary artery (LAD) followed by a 30-min
      reperfusion period. BK (1 ng.kg-1.min-1, n = 7), or its vehicle (Lactate Ringer,
      n = 7), infusions just distal to the left coronary ostium started 15 min before
      the LAD occlusion and were maintained throughout the experimental period. An
      epicardial vein, running parallel to the LAD was cannulated to enable the
      biochemical determinations. The effects of BK on ventricular arrhythmias, cardiac
      noradrenaline and lactate releases and creatine kinase activity were assessed.
      RESULTS: BK significantly reduced the amount of noradrenaline released at
      reperfusion by ischemic myocardium (from 82.1 +/- 31.7 to 11.9 +/- 9.6 ng.min-1),
      as well as plasma creatine kinase activity at 30 min of reperfusion. This is
      accompanied by a significant reduction in the incidence of reperfusion-induced
      sustained ventricular tachycardia. CONCLUSION: This suggests that the protective
      effect of bradykinin against reperfusion-induced sustained ventricular
      tachycardia could be associated with a reduction in cardiac noradrenaline
      release.

PMID- 7721231
TI  - Angiotensin II induces reduced oxytocin but normal corticotropin release in rats
      with lesions of the subfornical organ.
AB  - The subfornical organ (SFO) was suggested to be the site of the central nervous
      system which mediates the stimulatory effect of angiotensin II (AII) on
      corticotropin (ACTH) release. To verify this hypothesis, ACTH response to
      peripherally administered AII was measured in rats with electrolytic lesion of
      the SFO. Increase in ACTH levels in response to AII (0.5 micrograms/kg or 2.0
      micrograms/kg i.v. within 2 min) in conscious cannulated rats was dose-related
      and it was not affected by SFO lesion. The short infusion of AII (2.0
      micrograms/kg) was enough to induce an elevation in plasma oxytocin. Oxytocin
      response to AII was reduced while that of aldosterone and blood pressure was not
      modified by SFO lesion. Our data show that an intact SFO is needed for a full
      response of oxytocin but not of ACTH release to peripherally injected AII.

PMID- 7721232
TI  - Effects of oxodipine and elgodipine on (+)-[3H]-isradipine binding to cardiac and
      vascular membranes: cardiovascular selectivity.
AB  - We studied the effects of six dihydropyridines on the specific binding of (+)
      [3H]-isradipine to vascular (portal vein) and cardiac isolated membranes to
      achieve the relative cardiovascular selectivity of these compounds. Elgodipine,
      (+)-oxodipine and nifedipine had a significantly higher affinity for the vascular
      L-type calcium channel than for the cardiac calcium channel while nicardipine
      showed opposite properties. The other dihydropyridines (nitrendipine and (+)
      isradipine) had similar affinities for the cardiac and vascular calcium channels.
      As the membrane potential of isolated membranes is about 0 mV, these results
      suggest that the differences in binding of these dihydropyridines to L-type
      calcium channels in vascular and cardiac cells may be attributed to differences
      in the molecular structure of these calcium channels.

PMID- 7721233
TI  - Influence of 5-HT3 receptor antagonists in visceromotor and nociceptive responses
      to rectal distension before and during experimental colitis in rats.
AB  - We investigated the possible involvement of 5-HT3 receptors in the colonic motor
      alterations and abdominal pain evoked by rectal distension (RD) in rats, under
      normal and inflammatory conditions. Responses to RD were evaluated by
      electromyography in rats treated with 5-HT3 antagonists (ondansetron and
      cilansetron, 0.1 and 1 mg/kg, intraperitoneally), before and 3 days after
      intrarectal administration of TNB/ethanol. RD evoked a significant (P < 0.05) and
      gradual inhibition of the occurrence of colonic spike bursts (SB) and a gradual
      increase in abdominal SB from 11 mm in diameter on wards. Ondansetron and
      cilansetron (0.1 mg/kg) significantly reduced both the colonic (62 and 66%,
      respectively) and the abdominal response (28 and 61%, respectively) for an 11 mm
      diameter of RD. After TNB/ethanol, both colonic and abdominal responses to RD
      were significantly (P < 0.05) enhanced and appeared for a lower diameter (9 mm)
      (colon: 4.8 +/- 0.9 vs 8.4 +/- 1.1, abdomen: 7.7 +/- 1.5 vs 0.5 +/- 0.4).
      Cilansetron (0.1, 1 mg/kg) significantly (P < 0.05) attenuated the TNB-induced
      colonic motor inhibition, while ondansetron and cilansetron (0.1, 1 mg/kg)
      reduced the TNB-induced increase in abdominal response. We conclude that 5-HT and
      5-HT3 receptors mediate RD-induced viscerosensitive alterations in rats, both in
      normal conditions and during TNB-induced rectocolitis. However, the relative
      efficacy of the 5-HT3 receptor antagonists depends on the experimental conditions
      (intact or inflamed bowel) and does not appear to increase with the dose.

PMID- 7721234
TI  - Gallium chloride effects on neonatal rat heart cells in culture, in standard and
      oxidative conditions.
AB  - The effects of gallium chloride (GaCl3) at 7.17, 28.68 and 114.7 microns (0.5, 2
      and 8 mg/l of Ga3+) were checked in cardiac cells derived from 2-4 day-old
      newborn rats, cultured for 72 h in Eagle's minimum essential medium (MEM),
      enriched with 10% foetal calf serum (v/v) and 2 mM of glutamine at 37 degrees C,
      with 95% air plus 5% CO2. After 3 hours of standard culture conditions (MEM with
      glucose 5 mM), Ga treatment induced an increase of glycogen stores without any
      influence on ATP, ADP, and AMP concentrations. A slight and transient decrease in
      the beat rate was noted after 15 min of exposure to GaCl3 at all concentrations,
      whereas there was no difference in the beat rate nor in the cell contraction
      amplitude after 3 hours of exposure. After 1.5 h in conditions of oxidation
      (Tyrode solution without glucose, FeCl2 20 microM, ascorbic acid 0.2 mM), GaCl3
      at 8 mg/l decreased the malondialdehyde (MDA) production as assessed by the
      decrease of intracellular concentrations and the decrease of its release in the
      supernatant. The decreased MDA production following oxidative stress, the
      increase in glycogen stores in normal oxygen concentrations, as well as the
      maintenance of ATP concentrations and the lack of any chronotropic effect induced
      by GaCl3 suggests a protective rather than a deleterious cardiac effect.

PMID- 7721235
TI  - Treatment of common bile duct stones. A consensus report.

PMID- 7721236
TI  - Gastric cancer surgery in patients aged at least 80 years old.
AB  - Fifty-six patients with gastric cancer who were at least 80 years of age (range
      80-88) (Group 1) were retrospectively investigated and compared with younger
      patients. The resectability rate was 80% (45/56) in Group 1, 88% (331/373) in
      Group 2 (patients aged between 70 and 79) and 91% (992/1,087) in Group 3
      (patients aged under 70 years). Of the cases resected, 73% had advanced cancer in
      Group 1, 61% in Group 2 and 55% in Group 3. Total gastrectomy was performed in
      only 11% of the resected cases in Group 1, in 25% of those in Group 2 and in 33%
      in Group 3. Of these, combined resections were employed in none of the patients
      in Group 1, in 38% of those in Group 2 and in 47% of those in Group 3.
      Pathologically, 78% of Group 1 cancers were of the differentiated type, 68% of
      Group 2 and 49% of Group 3 cancers (Group 1: Group 3, p < 0.001). R3 gastrectomy
      was performed for advanced cancer in none of the patients in Group 1, in 21% in
      Group 2, and in 39% of those in Group 3. In resected early cancers, the lymph
      node metastasis (n) rate was 0% for Group 1, 10% for Group 2, and 9% for Group 3.
      In the advanced cases, n(+) was 67% for Group 1, 65% for Group 2, and 73% for
      Group 3. Postoperative complications occurred in 25% of Group 1 and in 12% of
      Group 2 patients. Anastomotic leakage occurred in 4% of Group 1 and in 5% of
      Group 2 patients. The 5-year-survival rate was 47% for all resected cases in
      Group 1, and 68% for Groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721237
TI  - Billroth II resection with modified Nissen duodenojejunostomy for duodenal ulcer
      hemorrhage associated with duodenal stricture.
AB  - Between January 1988 and December 1992, six patients presenting with chronic
      duodenal ulcer disease, long segment duodenal stricture, gross gastric dilatation
      and Forrest Ia hemorrhage from penetrating posterior duodenal wall ulcer were
      managed by oblique duodenal transsection, suture ligation of arroded
      pancreaticoduodenal vessel, classic Billroth II resection, Nissen
      duodenojejunostomy and a Tomoda valve disconnecting the Nissen anastomosis from
      the gastroenterostomy, -resulting in a functional "uncut" Roux anastomosis. The
      procedure was expeditious and safe in this patient population, with an uneventful
      recovery and satisfactory functional results.

PMID- 7721238
TI  - Treatment of bleeding peptic ulcer by bilateral truncal vagotomy via a
      transpleural thoracoscopic approach and laparoscopic pyloromyotomy.
AB  - Six cases of recurrent bleeding duodenal ulcer were treated by bilateral truncal
      vagotomy via a right transpleural thoracoscopic approach and laparoscopic
      pyloromyotomy at Tainan Municipal Hospital. The vagus nerves were completely
      transected, which was proved by pathology. Basal acid output and insulin
      stimulated maximum acid output were reduced by 68%-77% and 87%-92%, respectively,
      after vagotomy. On the other hand, there was no delay in gastric emptying on the
      basis of either patients' complaints or an upper gastrointestinal series of x
      rays. Transpleural thoracoscopic bilateral truncal vagotomy and laparoscopic
      pyloromyotomy are safe, effective and offer more complete transection of the
      vagus nerves in treatment of complicated peptic ulcer. In addition, this new
      technique provides shorter hospitalization and an earlier convalescence.

PMID- 7721239
TI  - Duodenitis--distinguishing features in a retrospective endoscopic and
      histological study.
AB  - Routine films of 596 upper GI endoscopies with the diagnosis of duodenitis were
      reviewed and a classification was made into granular (G), multi-polypoid (MP),
      reddened (R) and erosive (E) types. Two hundred and thirty-four histological
      specimens from 117 of the patients, as well as 100 specimens from 50 controls,
      were analyzed for villous obliteration, Brunner's gland dilatation and mucus
      depletion, erosion, mucosal hemorrhage and edema, atypia of the surface
      epithelium and gastric surface epithelial metaplasia. Inflammatory cell counts
      for polymorphonuclear and mononuclear cells in the epithelium, in the lamina
      propria together with a histological score was also made. On the basis of this
      study and a review of classifications of duodenitis in the literature, it is
      concluded that some endoscopical features like erosions and redness may represent
      more acute phases of duodenitis, mucosal elevations representing more
      hyperplastic changes and that the endoscopic classification into G, MP, R and E
      types seem relevant to use in clinical practice.

PMID- 7721240
TI  - Postoperative alkaline reflux gastritis following vagotomy.
AB  - This study was undertaken to evaluate the incidence and severity of postoperative
      alkaline reflux gastritis in 798 symptomatic duodenal ulcer patients who had
      undergone vagotomy. The condition was identified on the basis of the unique
      endoscopic and histological findings in 116 (14.5%) of them. It was more frequent
      and severe in patients with truncal vagotomy and gastrojejunostomy than in those
      with truncal vagotomy and pyloroplasty, while it was not at all observed in cases
      with proximal gastric vago-tomy, the symptoms depended on the preoperative
      history of the ulcer disease and the patient's age at the time of surgery, but
      did not always correspond with the degree of histological findings. The location
      of the gastrojejunostomy and the size of the pyloroplasty stoma had an influence
      on the incidence of the syndrome. Helicobacter pylori was found more frequently
      in biopsy specimens from patients with severe symptoms (30.3%), but was present
      in only 14.6% of the total number of the patients with postoperative alkaline
      reflux gastritis after vagotomy.

PMID- 7721241
TI  - Effect of Helicobacter pylori on dbc-AMP stimulated acid secretion by human
      parietal cells.
AB  - This study examines the effect of different H.p. strains (A-D) on dbc-AMP
      stimulated acid secretion by human parietal cells in vitro. H.p. strains A and D
      reduced acid secretion dose-dependently between 20 and 80%. In contrast, H.p.
      strains B and C had little or no effect. We conclude that H.p. strains vary in
      their ability to suppress acid secretion, and that the site of inhibition lies
      beyond the c-AMP level, possibly involving the K+H(+)-ATPase of the parietal
      cell. Interference with acid secretion may facilitate H.p. colonization of the
      stomach and may prove to be an important pathogenetic factor.

PMID- 7721242
TI  - Is Crohn's disease caused by antibiotics?
AB  - The increase in CD that has taken place over the last 50 years has paralleled the
      increasing use of antibiotics in human and veterinary medicine. Insufficient
      doses of antibiotics can induce a capacity for toxin production in bacteria, or
      can make them invasive. Prior antibiotic therapy also promotes the outbreak of CD
      to a statistically demonstrable extent. It may clearly be assumed that CD is
      caused in genetically susceptible persons by intestinal bacteria whose biological
      (but not morphological) properties have been altered by antibiotics.

PMID- 7721243
TI  - Plasma somatostatin levels in ulcerative colitis.
AB  - The circadian (24 hour) rhythmicity of somatostatin in healthy subjects and
      patients with ulcerative colitis (UC) was studied and established. UC patients
      were found to have a higher 24-hour amplitude, a higher average level and a
      longer peak level phase of plasma somatostatin. This finding may indicate a
      defensive role of somatostatin in inflammatory bowel disease.

PMID- 7721244
TI  - Enteral and parenteral anti-endotoxin treatment in experimental colitis.
AB  - Systemic endotoxemia has been described in ulcerative colitis and Crohn's disease
      and shown to correlate positively with disease activity and the extent of
      intestinal ulceration. This study evaluated the efficacy of antibiotic and anti
      endotoxic treatment in reducing systemic endotoxemia in a hapten-induced rat
      model of colitis. Enteral administration of paromomycin was associated with a
      significant reduction in systemic endotoxin concentrations (7.4 +/- 1.2 pg/ml)
      when compared with controls (39.8 +/- 12.6 pg/ml; p = 0.032). Intravenous
      injection of taurolidine was also found to significantly reduce systemic
      endotoxemia (3.1 +/- 1.3 pg/ml) in comparison with controls receiving saline
      injection (17.5 +/- 4.2 pg/ml; p = 0.008). Enteral neomycin, parenteral polymyxin
      or metronidazole and cefuroxime were ineffective anti-endotoxin treatments in
      this model. Enteral paromomycin or parenteral tauro-lidine therapy are potential
      methods of preventing and treating systemic endotoxemia in patients with
      inflammatory bowel disease.

PMID- 7721245
TI  - The effect of epidural morphine on human intestinal motility in the early
      postoperative period.
AB  - The early postoperative recovery of intestinal motility and the response of
      motility to epidural morphine were investigated in 20 patients. Periodic motor
      activities in the jejunum were recovered within 32 hours in all cases. The length
      of these cycles increased gradually from the 1st (23.2 min) to the 4th (41.7 min)
      postoperative day. Morphine and lignocaine were given through an epidural
      catheter. Morphine induced premature migrating motor complexes (MMC) in all
      cases, whereas lidocaine failed to evoke this response in every case. The mean
      duration (19.8 min) and maximal amplitude (62.8 mmHg) of the burst activities
      induced by morphine were significantly longer and higher than those occurring
      spontaneously (7.7 min and 35.6 mmHg, respectively). The intervals between the
      induced and the subsequent spontaneous contractions were the same as the
      intervals between spontaneous contractions. These observations indicate that
      epidural morphine induced premature MMC without interrupting recovery patterns
      from postoperative gastrointestinal paralysis.

PMID- 7721246
TI  - OK-432 chemical pleurodesis for the treatment of persistent chylothorax.
AB  - A 52-year-old woman with thoracic esophageal carcinoma was admitted to our
      hospital. Standard radical esophagectomy was carried out via a right
      posterolateral thoracotomy and laparotomy. A drainage tube was removed from the
      right side of the chest on the 9th postoperative day. Three days later a chest
      roentgenogram showed massive left pleural effusion, and a tube was inserted into
      the left pleural cavity. The volume of the effusion was 900 ml/day and
      chylothorax was diagnosed. Conservative therapy was applied for 30 days, but
      chyle leakage persisted. Intra-pleural infusion of OK-432, a Su-strain of
      Streptococcus pyogenes, and doxycycline hydrochloride was carried out to seal the
      leakage point. The effusion stopped immediately after the procedure. There were
      no major side effects. This procedure should be considered the treatment of
      choice for patients with persistent chylothorax not responding to initial
      conservative management.

PMID- 7721247
TI  - Delayed spontaneous opening of a self-expanding metal stent bridging a malignant
      esophageal stenosis.
AB  - We report on a case of an 85-year-old man with dysphagia who suffered from a
      stenosing esophageal adenocarcinoma that could not be treated by surgery. The
      tumor demonstrated circumferential growth and extended from 14 to 22 cm from the
      incisors. There were no esophago-tracheal fistulas. The stenosis could be
      negotiated with the endoscope. Under fluoroscopic guidance, a self-expanding
      Strecker stent was placed in the stenosed area with no prior dilatation. After
      releasing the stent an x-ray revealed a twisted and wrinkled stent which had
      expanded to only half of its maximum diameter. The patient's symptoms had not
      improved. Four days later dysphagia resolved when the stent spontaneously
      corrected its position and was found to be maximally expanded. On the basis of
      this observation it may be concluded that, at least in some cases, self
      correction of an initially unsatisfactory positioning of a Strecker stent may be
      expected, even after four days.

PMID- 7721248
TI  - Splenomegaly and variceal bleeding--hemodynamic basis and treatment implications.
AB  - Splenectomy and splenic embolization have been advocated as definitive therapy in
      cirrhotic patients bleeding from varices. While splenomegaly is commonly
      associated with portal hypertension, no clear hemodynamic link between portal
      pressure and splenic enlargement has yet been established. In an effort to
      clarify the hemodynamic significance of splenomegaly in portal hypertensive
      patients the relationship between spleen size and portal pressure was
      retrospectively reviewed and the contribution of splenic inflow to portal
      hypertension prospectively studied. In 50 consecutive cirrhotic variceal bleeders
      studied angiographically, there was no correlation between spleen size and
      corrected sinusoidal pressure. Portal pressure was then prospectively measured
      before and after splenic vein clamping in 12 cirrhotic patients undergoing distal
      splenorenal shunt. No significant pressure drop occurred following elimination of
      splenic venous flow. On the basis of these data, there would appear to be no firm
      hemodynamic basis for splenectomy or splenic embolization alone in the
      unselective management of cirrhotic patients with variceal bleeding.

PMID- 7721249
TI  - Percutaneous transhepatic portacaval shunt for high-risk esophageal varices.
AB  - Percutaneous transhepatic portacaval shunt (PTPS) was performed in a patient with
      high-risk esophageal varices prior to sclerotherapy. PTPS was accomplished with
      the aid of two catheters. The first catheter was placed in the right hepatic vein
      under ultrasonographic guidance, and the second was placed in the portal vein.
      The two catheters were then connected together. The color of the esophageal
      varices changed from blue to white, and serum protein levels were increased 8
      weeks after PTPS. Sclerotherapy was then performed without any difficulty. PTPS
      is the easy and quick method of performing a portacaval shunt and may have
      importance for the management of patients with high-risk esophageal varices prior
      to the treatment of sclerotherapy or liver transplantation.

PMID- 7721250
TI  - Lower esophageal sphincter pressure after subtotal gastrectomy and postoperative
      reflux esophagitis.
AB  - Although reflux esophagitis after subtotal gastrectomy has been noticed by
      surgeons, the mechanism of its development is obscure. This study was undertaken
      with the aim of clarifying the role of the lower esophageal sphincter in the
      development of this abnormality. Manometric studies were carried out on 42
      patients with gastric cancer, and on 19 with cholelithiasis. The lower esophageal
      sphincter pressure was measured using a catheter tip pressure transducer and a
      rapid pull-through technique, and the results presented as the mean of three
      measurements. The technical error of this experiment was estimated to be within 2
      mmHg by a study of the cholecystectomy patients. After gastrectomy, the lower
      esophageal pressure decreased in 17 patients, increased in 4 and remained
      unchanged in 21. A more pronounced decrease in the lower esophageal sphincter
      pressure was found after Billroth II. Clinical evaluation of the 42 patients
      revealed symptoms of postgastrectomy regurgitation in 10. Preoperatively, these
      10 had lower values of the lower esophageal sphincter pressure followed by a more
      marked postoperative decrease, as compared with the patients with no
      regurgitation symptoms. Oral administration of a test meal revealed regurgitation
      after subtotal gastrectomy. This study suggests that a low value of the pre
      operative lower esophageal sphincter pressure, a marked decrease in the pressure
      after gastrectomy, and Billroth II anastomosis, may be factors that predispose to
      regurgitation.

PMID- 7721251
TI  - Rupture of an amebic liver abscess into the pericardium. Presentation of a case
      and review of current management.
AB  - An unusual case of amebic liver abscess that ruptured into the pericardial cavity
      is presented. This complication of amebic disease is extremely rare, and fatal.
      Chest X-ray and CT scan were performed for diagnosis. Pericardectomy with
      surgical drainage was performed; unfortunately, the patient died of massive
      pulmonary emboli.

PMID- 7721252
TI  - Leiomyomas of the small bowel: a rare cause of massive and recurrent
      gastrointestinal bleeding. Case report.
AB  - Three cases of leiomyoma of the small bowel presenting with recurrent
      gastrointestinal bleeding diagnosed angiographically in the preoperative period,
      are discussed. Selective visceral angiography seems to be the most sensitive
      radiological examination. New types of enteroscopes are being developed.

PMID- 7721253
TI  - Endocrine Functions and Ageing. Proceedings of the 37th International Henri
      Pierre Klotz Symposium. Paris, May 5-6, 1994.

PMID- 7721254
TI  - Estrogens and progestins in postmenopausal women: influence on lipid parameters
      and cardiovascular risk.
AB  - Postmenopausal women are 2-3 times more likely to have a heart attack than
      premenopausal women. According to the results of the Framingham study, angina is
      one of the main manifestations of coronary heart disease in women, whereas
      myocardial infarction and sudden death are more frequent in men. Cigarette
      smoking, high blood pressure and hypercholesterolemia are major risk factors for
      coronary heart disease in both men and women, while diabetes mellitus and hypo
      high-density lipoproteinemia are more clearly associated with cardiovascular
      disease in women than in men. Endogenous and exogenous hormones may be a major
      determinant of the cardiovascular risk in women. Premenopausal women have a
      considerably lower incidence of coronary heart disease than postmenopausal women,
      and estrogen therapy is associated with a reduced risk in the latter. Part of
      this protective effect seems to be due to the influence of estrogen therapy on
      lipoprotein metabolism, i.e. a decrease in LDL cholesterol and an increase in HDL
      cholesterol. Progestins, to an extent which depends on their androgenic potency,
      have the opposite effects. A large study (the Postmenpausal Estrogen Progestin
      Intervention Trial) has been launched to test the effect of the estrogen
      progestin combination on various cardiovascular risk factors.

PMID- 7721255
TI  - Hormonal substitution in older men.
AB  - The biological bases of endocrine alterations in ageing men are now well
      identified: progressive impairment of testicular function, decline in growth
      hormone (GH) secretion with decreased insulin-like growth factor-I (IGF-I)
      levels, and reduced adrenal androgen secretion. Insulin resistance and glucose
      intolerance also accompany male ageing. The mechanisms of these age-related
      changes are still unknown. There are preliminary results on the effects of
      hormonal replacement therapy in older males with mild hypogonadism or decreased
      IGF-I levels. Controlled placebo studies will in the future define the risks and
      benefits of long-term administration of androgens, GH or GH-releasing hormone in
      these patients. In view of the severe potential side effects, the generalized use
      of hormonal substitution in elderly men cannot, for the moment, be recommended.

PMID- 7721256
TI  - Effects of ageing on endocrine and neuroendocrine rhythms in humans.
AB  - Biological rhythms in blood variables are now fairly well documented in young
      healthy adults whereas reports in elderly subjects are few for obvious reasons
      including the difficulty of setting up a group of elderly subjects comparable in
      age and social background and moreover free of major liver, heart, kidney, bone
      or any other degenerative disease and consequently not requiring medication. We
      have observed that the parameters characteristic of the biological rhythm may be
      modified with ageing. However, the modifications are different from one function
      or variable to the next. Differences in acrophases, mesors and amplitudes could
      be demonstrated. For instance the acrophase may be phase-advanced in the elderly
      for plasma cortisol, DHEA-S, 18-OHDOC, the amplitude may be modified for
      testosterone, 18-OHDOC, proteins, melatonin, gonadotrophins. The administration
      as a function of time of drugs or agents used as a diagnostic tool made it
      possible to ascertain the importance of the time structure in this field. Both
      validity and interpretation of such administration depend upon the timing of the
      agent administration in the 24-hour scale. Therefore, the temporal organization
      of the subjects undergoing such treatments should be taken into account. In the
      near future this kind of investigation on various biological variables may lead
      to an improvement of the desired drug effects in elderly patients.

PMID- 7721258
TI  - Ageing of the hypothalamo-pituitary-testicular axis in men.
AB  - In distinction to the course of reproductive ageing in women, men do not
      experience a rapid decline of Leydig cell function or irreversible arrest of
      reproductive capacity in old age. Hence, strictu sensu, the andropause does not
      exist. Nevertheless, both spermatogenesis and fertility as well as Leydig cell
      function do decline with age, as shown by a decrease of +/- 35% of total and of
      50% of free testosterone levels between the age of 20 and 80 years. The origin of
      this decline of Leydig cell function resides on the one hand in the testes, and
      is essentially characterized by a decreased number of Leydig (and Sertoli) cells
      and on the other hand in the hypothalamo-pituitary complex characterized by a
      decreased luteinzing hormone (LH) pulse amplitude, LH pulse frequency being
      maintained. As the responsiveness of the gonadotrophs to gonadotropin-releasing
      hormone (GnRH) remains unimpaired, one may assume that the amount of GnRH
      released at each pulse is also reduced, possibly as the consequence of a
      reduction of the cellular mass of GnRH neurones. Plasma levels of testosterone
      below the lower normal limit occur, however, only in a minority of elderly men
      from 7% in the age group 40-60, to 20% in the age group 60-80 and 35% in the age
      group over 80 years old. Factors influencing testosterone levels in elderly men
      are multiple: hereditary, environmental (obesity, stress), psychosocial
      (depression, smoking, drugs) or socioeconomical (diet, hygiene). Whether these
      elderly men should be substituted with androgens remains controversial.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7721257
TI  - Effects of ageing on modulation of hormonal secretions by sleep and circadian
      rhythmicity.
AB  - Circadian rhythmicity persists in healthy elderly subjects but a number of 24
      hour rhythms are dampened and/or advanced in old age. The tendency for earlier
      sleep onset, earlier morning awakening and a more fragmented and more shallow
      sleep period is representative of these alterations. Other overt rhythms which
      have been shown to be of lower amplitude and/or phase-advanced are those of body
      temperature and of the peripheral levels of hormones such as cortisol, melatonin,
      TSH, testosterone, prolactin and GH. Mean hormonal levels are generally
      decreased, but overall cortisol secretion is increased with ageing. These
      modifications are likely to be partially due to alterations of the circadian
      central nervous system processes controlling circadian rhythmicity and sleep.

PMID- 7721259
TI  - Pituitary-thyroid axis and immune system: a reciprocal neuroendocrine-immune
      interaction.
AB  - A good body of experimental and clinical results has supported the existence of
      numerous reciprocal interactions among the nervous, endocrine and immune systems.
      Increasing evidence has been accumulated in the last years on the interaction
      between pituitary-thyroid hormones and the immune system on the basis of either
      the existence of receptors for thyreotropic and thyroid hormones on lymphocytes
      or the frequent immune alteration in physiological and pathological fluctuations
      of thyroid hormones. The data were obtained either in animals with experimentally
      induced hyper- or hypothyroidism or in humans with various hyperthyroid or
      hypothyroid situations. Conversely, immune-derived products such as lymphokines
      and monokines have been shown able to influence the pituitary-thyroid axis
      modulating either the thyroid hormone levels or the hormone/cytokine production
      by thyrocytes. The present paper aims at summarizing the data available on the
      existence of thyroid-immune interactions, and at analyzing the possible
      integration between pituitary-thyroid hormones and immune factors in favoring the
      development and maintenance of both thymic and peripheral immune efficiency. The
      relevance of pituitary-thyroid-immune interactions is discussed for its
      implication in the ageing process.

PMID- 7721260
TI  - Somatotropic dysregulation in old mammals.
AB  - In old mammals, including humans, the spontaneous growth hormone (GH) secretory
      pattern is markedly reduced resulting in lower amounts of GH released over 24 h,
      and the GH response to administration of GH-releasing hormone (GHRH) is reduced.
      In agreement with these in vivo findings, an impaired responsiveness to GHRH is
      evident in the pituitary of old male and female rats in vitro, and this is linked
      with a diminished stimulation of adenylate cyclase by GHRH. The poor GH
      responsiveness to GHRH in old mammals, which in the rat is coupled to a defective
      number of GHRH receptors in the somatotrophs, is likely due to a primary
      deficiency of GHRH availability, as implied by the diminished GHRH
      immunoreactivity and gene expression in and GHRH release from the hypothalamus of
      old rats. Attempts have been made to stimulate the sluggish somatotrophic
      function in elderly humans and dogs using GHRH; in either species positive
      results were obtained though, overall, it would seem that the GHRH hypofunction
      does not entirely account for the GH hyposecretory state during ageing.
      Concerning somatostatin, although the expression of this peptide decreases with
      age in the rat hypothalamus, secretion and activity of this hormone is increased,
      resulting in an altered relationship between GHRH and somatostatin gene
      expression and secretion. It is likely that defects, especially in
      catecholaminergic and cholinergic neurons, are instrumental in altering specific
      peptidergic neurons. Reportedly, catecholamines induce GH release by stimulating
      GHRH neurons and inhibiting somatostatin-releasing neurons; acetylcholine
      stimulates GH release via muscarinic receptors, in this way inhibiting the action
      of somatostatin neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721261
TI  - Nutrition of the elderly: a challenge between facts and needs.
AB  - Interactions between nutrition and the ageing process are a fascinating field of
      research. The assessment of the nutritional status is an important part of
      medical examination. Generally it is assumed that energy intake and energy
      expenditure decrease with age. In fact they vary widely and are very different in
      healthy, in sick or in institutionalized elderly. Nutritional requirements depend
      on many social and physiological factors in the free-living elderly population.
      Surveys indicate that dietary requirements are qualitatively grossly comparable
      to those in middle-aged adults. However the elderly are particularly at risk of
      marginal deficiencies of vitamins and trace elements. Today the early recognition
      of malnutrition is an important challenge. Its prevention may influence the
      evolution of nonspecific intercurrent disease and restore immunocompetence.
      Another challenge is to promote health by adequate recommendations in order to
      prevent deficiency diseases and to increase longevity. Some studies suggest that
      nutrition-based preventive medicine remains useful in the elderly. Caloric
      restriction, weight loss in case of obesity, decrease in blood lipids, increase
      in calcium intake which depend mainly of prior nutritional habits may have an
      effect in the elderly. However, prevention of protein caloric malnutrition is
      more relevant in the elderly.

PMID- 7721262
TI  - Glucose handling, diabetes and ageing.
AB  - The relationship between ageing and glucose homeostasis is still an open debate.
      In fact, the mechanisms by which glucose metabolism is progressively impaired
      with increasing age are not completely understood. In the present report we have
      reviewed the possible mechanisms (impaired insulin secretion and action, role of
      the environmental factors) which may lead to the impairment in glucose handling
      associated with ageing. We also point out that not all aged subjects are glucose
      intolerant; in fact, it has been suggested that only those aged subjects who
      present more than one pathological finding do in fact develop impaired glucose
      handling.

PMID- 7721263
TI  - Cardiovascular risk at the menopause--role of sexual steroids.
AB  - From epidemiological and experimental evidence it has been concluded that ovarian
      steroids have a large variety of cardiovascular effects. Among these are a direct
      action on the vascular wall, alterations in hemodynamics, modification of protein
      metabolism involved in the arteriosclerosis process, and alterations in the risk
      of cardiovascular morbidity and mortality. Some of the earlier epidemiological
      studies indicated an increased risk of cardiovascular disease (CVD) in estrogen
      users, but later on the majority of the published studies reported consistently a
      striking decrease in CVD by about 50%. The consistency in the positive results
      observed in successive epidemiological reports from various countries strongly
      suggest a protective effect of hormone replacement therapy on CVD morbidity.
      However, the direct demonstration of a protective effect of estrogens on CVD
      morbidity and mortality can only be made by long-term prospective controlled
      studies.

PMID- 7721264
TI  - Thyroid autoimmunity and ageing.
AB  - Ageing is associated with the appearance of several serum autoantibodies,
      including thyroid autoantibodies. The biological and clinical significance of
      this phenomenon is still unknown, since, with the exception of primary myxedema,
      the prevalence of clinically overt thyroid autoimmune diseases is not increased
      in the elderly. The peculiar link between autoimmune thyroid failure and ageing
      is also underscored by the high prevalence of subclinical hypothyroidism in
      elderly subjects with positive serum thyroid autoantibodies, and could be the
      consequence of preferential age-dependent expression of destructive effector
      mechanisms and/or increased target gland susceptibility. Thyroid autoimmunity and
      subclinical hypothyroidism have also been implicated in the pathogenesis of other
      age-associated disorders, in particular coronary heart disease. Interestingly,
      recent data from our laboratories showed that thyroid autoantibodies are rare in
      healthy centenarians and in other highly selected aged populations, while they
      are frequently observed in unselected or hospitalized elderly. Taken together,
      these data suggest that thyroid autoimmune phenomena are not the consequence of
      the ageing process itself, but rather might be related to age-associated disease.

PMID- 7721265
TI  - Paracrine regulation of bone remodeling.
AB  - Bone remodeling tightly couples resorption and formation in a cell unit called
      bone modeling unit (BMU). The activity of the BMU leads to a negative balance of
      bone mass in adults with physiological osteopenia. The regulation of the BMU is
      done at a local level by paracrine and autocrine factors such as cytokines and at
      an endocrine level by hormones. The hormonal level has been widely discussed in
      previous reviews and recent studies focus on the relations between hormonal
      triggers and cytokine-mediated responses to their stimulations. This review is
      dedicated to the means of coupling osteoblasts and osteoclasts and the
      recruitment of early cell precursors that originate in the hematopoietic bone
      marrow. Bone should be considered not only as an individual organ but as
      integrated in the bone-bone marrow organ.

PMID- 7721266
TI  - Calciotropic hormones and ageing.
AB  - Calcium availability is reduced in the elderly because not only of decreased
      dietary intake of calcium and vitamin D, but also reduced solar exposure and a
      decrease in the production of provitamin D by the skin. Moreover, calcitriol
      synthesis and calcitriol activity on calcium absorption by the small intestine
      are decreased with ageing. The age-related plasma parathormone increase enhances
      bone remodelling. The decrease of calcitonin secretion in the elderly is possibly
      related to a loss of sex steroids and calcitriol. 24-hour integrated growth
      hormone (GH) and insulin-like growth factor I concentrations are also decreased
      with ageing, but the effectiveness of GH therapy on bone mass in the elderly is
      still assumed.

PMID- 7721267
TI  - Ageing of the human hypothalamus.
AB  - The various hypothalamic nuclei show very different patterns of change in ageing.
      These patterns are a basis for changes in biological rhythms, hormones,
      autonomous functions or behavior. The suprachiasmatic nucleus (SCN) coordinates
      circadian and circannual rhythms. A marked seasonal and circadian variation in
      the vasopressin (AVP) cell number of the SCN was observed in relation to the
      variation in photoperiod. During normal ageing, the circadian variation and
      number of AVP-expressing neurons in the SCN decreases. The sexually dimorphic
      nucleus (SDN), intermediate nucleus or INAH-1 is localized between the supraoptic
      and paraventricular nucleus (PVN). In adult men the SDN is twice as large as in
      adult women. In girls, the SDN shows a first period of decreasing cell numbers
      during prepubertal development, leading to sexual dimorphism. During ageing a
      decrease in cell number is found in both sexes. The cells of the supraoptic
      nucleus and PVN produce AVP or oxytocin and coexpress tyrosine hydroxylase. These
      nuclei are examples of neuron populations that seem to stay perfectly intact in
      ageing. Parvicellular corticotropin-releasing-hormone (CRH)-containing neurons
      are found throughout the PVN. CRH neurons in the PVN are activated in the course
      of ageing, as indicated by their increase in number and AVP coexpression. Part of
      the infundibular (or arcuate) nucleus, the subventricular nucleus, contains
      hypertrophic neurons in postmenopausal women. The hypertrophied neurons contain
      neurokinin-B (NKB), substance P and estrogen receptors and probably act on LHRH
      neurons as interneurons. The NKB neurons may also be involved in the initiation
      of menopausal flushes. The nucleus tuberalis lateralis might be involved in
      feeding behavior and metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721268
TI  - Diagnostic procedures for osteoporosis in the elderly.
AB  - Several recent studies show that bone loss continues in the elderly, and that
      various regimens are still effective in the elderly to stop bone loss. Thus,
      diagnostic procedures for osteoporosis should be considered in elderly women,
      i.e. measurement of bone mass by dual energy X-ray absorptiometry of the hip,
      spine or forearm that have been shown to predict the subsequent risk of
      fractures. The rate of bone turnover, and therefore of bone loss, is quite
      variable from patient to patient and can be assessed with improved sensitivity
      and specificity with the new markers that are specific for bone formation and
      bone resorption.

PMID- 7721269
TI  - Treatment of bone in elderly subjects: calcium, vitamin D, fluor,
      bisphosphonates, calcitonin.
AB  - Several approaches may be suggested for prevention or treatment of senile
      osteoporosis. In elderly patients, an association of calcium and vitamin D
      supplementation has been shown to reduce nonvertebral fractures up to 40% over an
      18-month period. Calcitonin, given parenterally or nasally, may prevent further
      bone loss and has been reported to significantly decrease vertebral and hip
      fractures. This hormone also possesses an important analgesic effect. Fluoride
      salts are the most effective way to significantly increase bone mass, mainly at
      the trabecular site. The optimal doses and regimens remain to be clearly
      established. The use of new formulations like sodium monofluorophosphate are
      likely to facilitate the search of the optimal therapeutic window.
      Bisphosphonates are potent inhibitors of bone resorption. They have been shown to
      significantly increase trabecular bone mass without impairment of cortical bone.
      Their use may be associated with a significant decrease in vertebral fractures,
      mainly in patients with severe osteoporosis. The new, second and third generation
      of bisphosphonates (tiludronate, risedronate, alendronate) look extremely
      promising but their widespread use will only be possible after a confirmation of
      the absence of a deleterious effect on bone quality (alendronate) and after
      demonstration of a reduction in vertebral and/or hip fractures following a
      prolonged use.

PMID- 7721270
TI  - Retinoids and ageing.
AB  - The observation that topical retinoic acid could attenuate wrinkles and other
      features of skin photoageing has projected this molecule into the media
      spotlight. Behind this effect are in fact major basic biological issues related
      to the role of retinoids in tissue maintenance and their possible interference
      with the molecular biology of cellular ageing.

PMID- 7721271
TI  - Consequences of growth hormone deficiency in adults and the benefits and risks of
      recombinant human growth hormone treatment. A review paper.
AB  - Growth hormone deficiency (GHD) in adults is now recognized as a specific
      clinical syndrome with characteristic symptoms and signs. Thus, the patients are
      overweight, have an abnormal body composition (excess body fat and a decrease in
      the extracellular water volume) and a low bone mineral content compared to
      normals. Furthermore, the GHD patients have lipid abnormalities, decreased
      insulin sensitivity and a decreased fibrinolysis. Finally, the 'quality of life'
      is low in terms of energy and social life. Short- and long-term studies with
      recombinant human GH (rhGH) treatment have shown normalization of body
      composition, increase in the lipid pattern and marked improvement of the
      psychological well-being. The treatment seems safe with no serious side effects
      reported. In analogy with other hormonal replacement therapies, the rhGH dose
      should be individualized.

PMID- 7721272
TI  - Genetic evidence on modern human origins.
AB  - A review of genetic evidence leads to the following conclusions concerning human
      population history: (1) Between 33,000 and 150,000 years ago the human population
      expanded from an initial size of perhaps 10,000 breeding individuals, reaching a
      size of at least 300,000. (2) Although the initial population was small, it
      contained at least 1000 breeding individuals. (3) The human races separated
      several tens of thousands of years before their separate expansions. (4) Before
      their expansions the separate racial populations were small. These inferences are
      inconsistent with both the multiregional and the replacement models of modern
      human origins. They support the "weak Garden of Eden" hypothesis, which holds
      that the human populations separated some 100,000 years ago but did not expand
      until tens of thousands of years later.

PMID- 7721273
TI  - Assortative mating: sex differences in mate selection for married and unmarried
      couples.
AB  - We studied assortative mating for age, nationality, educational level, and
      occupational level in married and unmarried parents to test evolutionary models
      explaining mate selection among humans. We used the marriage and birth registers
      of the Venezuelan population to compare recently married, fertile married, and
      fertile unmarried couples. The results show significant assortative mating for
      all variables, but the results are strongest for age and education. These data
      suggest that (1) selection criteria based on age vary along the life cycle and
      differ between married and unmarried couples; (2) male's socioeconomic status is
      more related to the availability of younger females among unmarried couples
      compared with married couples, except for young couples; and (3) female selection
      for better (more educated and/or better employed) mates is stronger among married
      couples, whereas male selection for younger females or those showing actual
      reproductive potential is stronger among unmarried couples.

PMID- 7721274
TI  - a-b ridge count in a Basque population: fluctuating asymmetry and comparison with
      other populations.
AB  - We have analyzed the a-b ridge count and its fluctuating asymmetry in a sample
      (331 males and 290 females) from the Basque region of Alava province, Spain.
      Significant bimanual differences in the a-b ridge count are apparent only for
      females, and the sexual differences are significant for both hands. A comparison
      of the results in the Alava Basque population with results for other Basque
      populations showed sexual dimorphism. The results for fluctuating asymmetry do
      not support the hypothesis that if the regression of fluctuating asymmetry on the
      right and left hands is quadratic, the fluctuating asymmetry is a result of
      developmental homeostasis. Our data seem to indicate also that the factors that
      determine the a-b ridge count are canalized in females and males in the same way.

PMID- 7721275
TI  - Famine, third-trimester pregnancy weight gain, and intrauterine growth: the Dutch
      Famine Birth Cohort Study.
AB  - Data from the Dutch Famine Birth Cohort Study were analyzed to assess the
      influence of acute famine on the relation of maternal weight gain to birth
      weight, length, and ponderal index. Records were examined for 734 women receiving
      at least one month of prenatal care and delivering live-born singleton females at
      the University of Amsterdam Teaching Hospital between August 1944 and April 1946.
      This period preceded, encompassed, and followed the Hunger Winter, a severe
      famine. After adjusting for covariates, weight loss or low to moderate (< or =
      0.5 kg/week) weight gain was strongly associated with (p < 0.001 for each model)
      with offspring birth weight, length, and ponderal index and with trimester of
      famine exposure. At weight gains greater than 0.5 kg/week further weight gain was
      not associated with birth size. Among women losing weight or gaining < or = 0.5
      kg/week the association between third-trimester weight change and birth weight
      among mother-daughter pairs exposed to famine in early or mid-pregnancy was
      stronger than the association observed among the unexposed cohort or among those
      exposed only late in pregnancy. Our results suggest that acute maternal
      nutritional deprivation affects fetal growth only below a threshold and that,
      conversely, even after a famine period offspring birth size does not respond in a
      linear fashion to ad libitum maternal feeding.

PMID- 7721276
TI  - Univariate and bivariate admixture analyses of serum glucose and glycated
      hemoglobin distributions in a Jerusalem population sample.
AB  - Univariate and bivariate analyses of fasting glucose and glycated hemoglobin
      (HbA1c) levels and of glucose levels 2 hours after an oral glucose load test were
      performed in a random sample of the Jewish population of Jerusalem, aged 25-64
      years. Using ln-transformed data, we found that a mixture of two distributions
      fits the glucose data significantly better than a single distribution in the age
      groups 25-44 and 45-64 years. The fasting glucose results indicate that 1.1% of
      subjects aged 25-44 and 3.7% of subjects aged 45-64 without known diabetes come
      from an upper distribution with mean values of 154 mg/dl and 224 mg/dl,
      respectively. Estimates from the analysis of glucose levels after a load test
      indicate that an additional 2.1% of younger subjects and 3.8% of older subjects
      belong to a minor distribution with a high mean glucose value. The frequency
      distribution of HbA1c is also bimodal in all age groups. Yet the bimodality
      indicates that only 0.1% and 2.3% of subjects in the two age groups,
      respectively, come from minor distributions with mean levels of 13.0-15.7%,
      compared with HbA1c values of 5.0% and 5.3% for the main distributions. Using
      glucose levels, we found that specificity rates are consistently greater than
      99%, whereas sensitivity rates vary with age. The use of cutoff points suggested
      by the National Diabetes Data Group (140 mg/dl for fasting glucose level and 200
      mg/dl for glucose level after an oral glucose load test) indicates a lower
      sensitivity rate in the younger subjects with a minimal improvement among older
      subjects. A mixture of bivariate log-normal distributions fitted to the fasting
      and 2-hour glucose levels in subjects aged 45-64 indicates a larger proportion
      (6.3%) belonging to the minor distribution compared with those obtained when a
      single variable is used. Yet this combined score shows a low specificity rate. No
      similar improvement in separating "normal" from "abnormal" subjects is achieved
      when a mixture of bivariate distributions is fitted to the glucose and HbA1c
      variables. Admixture of glucose and HbA1c distributions is demonstrated.
      Bivariate analysis of these distributions does not, however, provide better
      discrimination of putatively abnormal subjects than univariate analysis.

PMID- 7721277
TI  - Haplotypes without children: PCR applied to close loci on individual human sperm.
AB  - Indirect evidence of interindividual variation of the recombination fraction is
      considerable, but as yet direct evidence is lacking. Such interindividual
      variation could explain the widely observed gametic association in the major
      histocompatibility complex (MHC) region. A possible approach to this is the
      application of the polymerase chain reaction to closely linked markers on
      individual sperm. The feasibility of this approach is investigated here. Three
      loci in the human MHC (chromosome 6) were used in this study. Two are
      polymorphisms identifiable by oligonucleotide dot blotting, and one is a
      microsatellite polymorphism. The genetic distances between these loci are 0.5 and
      1 centi-Morgan. We were able to double-type most cases for the two markers HLA
      DPB and HLA-DRB in single haploid cells. The rate of double typings is comparable
      with that expected from the hypothesis of independent failures at two loci.
      However, this rate of failure remains too great to allow an analysis of
      segregation because allele specific failure cannot be ruled out. All double and
      triple typings (implicating the microsatellite) were perfectly correlated with
      each other; thus no recombinations were identified. With such close markers
      recombination would have been surprising and may indicate an inherent accuracy of
      positive haplotyping.

PMID- 7721278
TI  - Population genetic study among the Orange Asli (Semai Senoi) of Malaysia: Malayan
      aborigines.
AB  - A population genetic study was undertaken to provide gene frequency data on the
      additional blood genetic markers in the Semai and to estimate the genetic
      relations between the Semai and their neighboring and linguistically related
      populations by genetic distance and principal components analyses. Altogether 10
      polymorphic and 7 monomorphic blood genetic markers (plasma proteins and red cell
      enzymes) were studied in a group of 349 Senoi Semai from 11 aboriginal
      settlements (villages) in the Pahang State of western Malaysia. Both the red cell
      glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase
      (PGD) loci reveal the presence of polymorphic frequencies of a nondeficient slow
      allele at the G6PD locus and a fast allele at the PGD locus. The Semai are
      characterized by high prevalences of ahaptoglobinemia and G6PD deficiency, high
      frequencies of HP*1, HB*E, RH*R1, ACP*C, GLO1*1, PGM1*2+, and GC*1F and
      corresponding low frequencies of ABO*A, HbCoSp, HB*B0, TF*D, CHI, and GC*2.
      Genetic distance analyses by both cluster and principal components models were
      performed between the Semai and 14 other populations (Malay; Javanese; Khmer;
      Veddah; Tamils of Malaysia, Sri Lanka, and India; Sinhalese; Oraon; Toda and
      Irula of India; Chinese; Japanese; Koreans) on the basis of 30 alleles at 7
      polymorphic loci. A more detailed analysis using 53 alleles at 13 polymorphic
      loci with 10 populations was carried out. Both analyses give genetic evidence of
      a close relationship between the Semai and the Khmer of Cambodia. Furthermore,
      the Semai are more closely related to the Javanese than to their close neighbors-
      the Malay, Chinese, and Tamil Indians. There is no evidence for close genetic
      relationship between the Semai and the Veddah or other Indian tribes. The
      evidence fits well with the linguistic relationship of the Semai with the Mon
      Khmer branch of the Austro-Asiatic language family.

PMID- 7721279
TI  - Factors affecting the sex ratio in humans: multivariate analysis of the Italian
      population.
AB  - Several studies have shown that the human secondary sex ratio is affected by a
      wide range of biological and environmental factors. Here, we describe a
      partitioning of the sex ratio variability as observed in the Italian population
      over the last two generations. This period has seen drastic changes in the
      environmental conditions of Italy. As a consequence, demographic and biological
      variables that can affect the sex ratio have also changed dramatically. In an
      attempt to isolate any specific effect, we used a stepwise multiple regression to
      analyze the covariation over time of the sex ratio and of relevant parameters,
      such as stillbirth rate, maternal age, firstborn proportion, and birth order. The
      results show that a quadratic function of the firstborn proportion and mother's
      age is a fairly good predictor of sex ratio values.

PMID- 7721280
TI  - Mortality in a migrating Mennonite church congregation.
AB  - Preston's two-census method of demographic estimation is applied to three pairs
      of reconstructed censuses from the records of a migrating Mennonite church
      congregation covering the period 1780-1890. The three pairs of censuses
      correspond to three periods (1780-1790, 1850-1860, and 1880-1890) and to stays in
      three settings (Prussia, Russia, and Kansas, respectively). The Mennonites' stay
      in Prussia was a period of hardship. In Russia they expanded their economic base
      and developed new farming methods, dramatically increasing their productivity.
      The Mennonites took these skills to Kansas, where they continued to be
      successful. The increase in life expectancy at age 5 corroborates this picture.
      The Prussian period exhibits the shortest life expectancy for both sexes. After
      the move to Russia, life expectancy increased for both sexes and continued to
      increase with the move to Kansas. The model also provides limited evidence for
      fertility depression following the move to Kansas.

PMID- 7721281
TI  - Population biology of human aging: methods of assessment and sex variation.
AB  - Biological age, as assessed by osteographic measurements of hand bones from
      radiograms, was estimated in about 7000 individuals belonging to 32 ethnic groups
      and samples and to 2 major human groups (Europeans and Asians). Individual ages
      in the total group varied between 16 and 99 years old. Our biological age measure
      is strongly correlated with chronological age of the individual (Pearson's r =
      0.78-0.80, p < 0.001), which renders the correlation amenable to fitting with a
      two-stage stochastic model. The following parameters of the model were estimated
      accordingly: t0 is the minimal age at which initial bone changes occurred, q is
      the probability that an individual will first develop involutive bone change at
      age ti > t0, and B is the rate of aging (bone change) per unit time. The
      parameters varied considerably within different populations, but only a few
      samples showed statistically significant sex differences for all three
      parameters. However, B was consistently higher among women than among men. Apart
      from that, the distributions of the observed biological age estimates adjusted on
      the expected biological age values reveal no differences between men and women in
      any of the studied samples or in the total population.

PMID- 7721282
TI  - HIV prevalence and risk behaviour among prostitutes and clients in Amsterdam:
      migrants at increased risk for HIV infection.
AB  - OBJECTIVES: To study groups of prostitutes and clients of prostitutes in order
      (i) to determine HIV prevalence and sexual risk behaviour, (ii) to determine
      differences between samples recruited within and outside a clinic for sexually
      transmitted diseases (STD) and (iii) to determine correlates of inconsistent
      condom use (ICU) among both groups. DESIGN: Participants were interviewed and
      anonymously tested for HIV-antibody; approximately half were recruited at a
      clinic for sexually transmitted diseases (STD) and half at prostitute working
      places. SETTING: An STD clinic and prostitute working places in Amsterdam in
      1991. SUBJECTS: 201 female prostitutes without a history of injecting drugs and
      213 male clients of female prostitutes. MAIN OUTCOME MEASURES: antibodies to HIV,
      consistency of condom use in commercial vaginal contacts in the preceding 6
      months. RESULTS: HIV prevalence was low: three prostitutes (1.5%; 95% CI 0.5
      4.6%) and one client (0.5%; 95% CI 0.1-3.3%) were infected. All three HIV
      positive prostitutes originated from AIDS-endemic countries, came to the
      Netherlands only recently and were recruited outside the STD clinic. Large
      differences between subgroups resulted from the two recruitment methods: while
      clients of prostitutes with relatively high risk behaviour were strongly
      represented among the STD clinic sample, high risk prostitutes were
      underrepresented in this sample. Consistent condom use (with 100% of contacts)
      was reported by 66% of prostitutes and 56% of clients of prostitutes.
      Inconsistent condom use was found to be high among prostitutes who had migrated
      from Latin America and among migrant clients of prostitutes. CONCLUSIONS: When
      monitoring HIV infection one must take into account imported cases. HIV
      prevention efforts should be particularly focused at prostitutes from Latin
      America and at clients of prostitutes who migrated to the Netherlands.

PMID- 7721283
TI  - Risk profiles for genital infection in women.
AB  - OBJECTIVE: To determine independent risks with predictive value for specific
      sexually transmitted diseases in women. DESIGN: A prospective study of reported
      sexual behaviour in patients who presented for screening and diagnosis of
      sexually transmitted diseases. SETTING: A genitourinary medicine clinic at the
      West London Hospital. SUBJECTS: 1025 consecutive newly attending patients who
      completed a sexual behaviour questionnaire between February and June 1982. MAIN
      OUTCOME MEASURES: Sexual behaviour reported by standardised self-administered
      questionnaire and sexually transmitted diseases diagnosed by routine clinical and
      laboratory methods. RESULTS: Independent risks for gonorrhoea were teenage (RR
      2.0), black race (RR 2.0), more than two partners in the past year (RR 2.2) and
      previous pregnancy (RR 2.1). Trichomoniasis (RR 2.5), chlamydial infection (RR
      1.8) and pelvic inflammatory disease (RR 4.8) also had significant predictive
      value. Conversely, gonorrhoea proved a risk for chlamydial infection (RR 2.1)
      together with age under 25 years (RR 2.3) and more than five partners in the
      previous year (RR 2.2). Ano-genital herpes was predicted by a total of more than
      10 sexual partners (RR 2.6) and by both anal (RR 2.2) and oral intercourse (RR
      2.9). Age under 25 years was the only independent risk for ano-genital warts (RR
      2.0). We found no evidence that either vaginal candidosis or bacterial vaginosis
      were sexually transmitted. The risk for any genital infection was increased by
      more than one sexual partner in the preceding year (RR 1.7) and black race (RR
      2.0). CONCLUSIONS: Sexually transmitted diseases show both similarities and
      differences in the risk factors associated with their transmission. These risk
      profiles facilitate the targeting of health education measures for those sections
      of the community at greatest risk and form a baseline for the future assessment
      of the effects of condom protected sexual intercourse and other safer sexual
      practices.

PMID- 7721284
TI  - Clinical presentation of genital warts among circumcised and uncircumcised
      heterosexual men attending an urban STD clinic.
AB  - INTRODUCTION: A recent study comparing heterosexual men with and without
      confirmed sexually transmitted diseases (STDs) in an urban STD clinic showed that
      uncircumcised men were less likely than circumcised men to have genital warts
      detectable by clinical examination (adjusted odds ratio 0.7, 95% confidence
      interval 0.4, 0.9). Based on these initial findings we hypothesised that the
      appearance and anatomic distribution of genital warts, and possibly treatment
      response, may be different for circumcised and uncircumcised men. METHODS: The
      anatomic location, appearance, number of warts, and response to treatment was
      investigated through review of medical records of 459 heterosexual men with
      genital warts detected in 1988. RESULTS: Age- and race-adjusted estimates
      indicated that among men with genital warts, warts were detected much more
      commonly on the distal penis--that is, the corona, frenulum, glans or urethral
      meatus-, among uncircumcised men (26%) than among circumcised men (3%) (OR 10.0,
      95% CI 3.9, 25.7). Where the appearance was specified, warts were more often
      described as condylomatous in uncircumcised men and slightly more often as
      papular in circumcised men. No significant difference between circumcised and
      uncircumcised men was seen in the number of return visits to the clinic for
      persistent warts after treatment with liquid nitrogen: 2.2 visits for 19
      uncircumcised men and 2.3 visits for 149 circumcised men. CONCLUSION: Circumcised
      men were more likely than uncircumcised men to have genital warts, but when
      present, warts were more often located on the distal portion of the penis among
      uncircumcised men. This paradox is not understood, but could reflect either
      nonspecific resistance to proximal penile warts conferred by the foreskin, or
      heightened susceptibility to various HPV types in uncircumcised men, some of
      which may confer subsequent immunity to genital warts.

PMID- 7721285
TI  - Mycoplasma genitalium: a cause of male urethritis?
AB  - BACKGROUND: Male urethritis may be caused by mycoplasmas. Since Mycoplasma
      genitalium has previously been isolated from the urethra of two men with non
      gonococcal urethritis (NGU), it was the aim of the study further to elucidate its
      role by measuring the prevalence of this organism in men with NGU. MATERIAL AND
      METHODS: The polymerase chain reaction was used. Two different sequences of the
      gene coding for the main adhesin MgPa were amplified. Urethral, rectal, and
      throat samples from 99 male sexually transmitted disease (STD) patients with and
      without urethritis were studied. RESULTS: M genitalium DNA was demonstrated in
      17/99 (17%) of the urethral swabs, but in none of the rectal and throat swabs.
      Significantly more patients with urethritis (13/52) were positive for M
      genitalium DNA than were patients without urethritis (4/47) (p < 0.03). In those
      with urethritis M genitalium DNA was found more often in Chlamydia trachomatis
      negative NGU (12/34) than in those with chlamydial NGU (1/14) (p = 0.05).
      Attempts to culture M genitalium from the PCR positive specimens were
      unsuccessful. CONCLUSION: M genitalium DNA was found significantly more often in
      male STD patients with non-chlamydial NGU than in men with chlamydial urethritis
      (p = 0.05) and in men without urethritis (p = 0.003), suggesting that M
      genitalium may be a cause of NGU. M genitalium DNA was not demonstrated in any of
      the throat or rectal swabsindicating that the urogenital tract is probably the
      primary site of infection or colonisation of this species.

PMID- 7721286
TI  - The absence of HPV DNA in genital specimens from infants.
AB  - OBJECTIVE: To identify the prevalence of HPV DNA using the polymerase chain
      reaction (PCR) in neonatal foreskin and cervical specimens obtained at necropsy.
      MATERIALS: Foreskin and cervical specimens were obtained from consecutive
      neonates who had autopsies performed at The Royal Women's Hospital, Melbourne,
      from June 1991 to February 1992. Specimens were analysed for HPV DNA using the
      polymerase chain reaction and the L1 consensus primers and generic probes.
      RESULTS: Specimens were obtained from 98 neonates, 52 males and 46 female. The
      mean gestational age of the neonates was 29 weeks (range 20-42). Eighty neonates
      died in utero, three during labour and 15 following delivery. Ninety four were
      delivered vaginally whilst four were delivered by caesarean section. Samples were
      collected a mean of 20 hours (range 2-48) from the time of delivery. In 30 cases
      there was evidence of autolytic change while in the remaining cases, the
      histology was well preserved. No evidence of HPV DNA was found in any of the
      samples using the L1 general primers (95% confidence interval 0-3.6%). Recent
      cervical cytology was available on 70 of the infant's mothers. Six had
      cytological evidence of HPV infection while the remainder were normal.
      CONCLUSIONS: HPV DNA is uncommonly detected (by PCR) in foreskin and cervical
      specimens obtained from neonates.

PMID- 7721287
TI  - Detection of varicella-zoster virus DNA using the polymerase chain reaction in an
      immunocompromised patient with transverse myelitis secondary to herpes zoster.
AB  - A case of herpes zoster transverse myelitis is described in which the clinical
      diagnosis was confirmed by demonstrating the presence of varicella-zoster virus
      (VZV) DNA in the cerebrospinal fluid (CSF) by amplification using the polymerase
      chain reaction. This case illustrates the potential role of the selective
      amplification of VZV DNA from CSF in contributing to the diagnosis of
      neurological complications associated with VZV infection.

PMID- 7721288
TI  - Lack of detection of human papillomavirus DNA in male urine samples.
AB  - OBJECTIVES: To evaluate polymerase chain reaction (PCR) methodology for the
      detection of urethral human papillomavirus (HPV) infection by examining urinary
      sediment from males. SETTING: Department of Genitourinary Medicine, Leeds General
      Infirmary. SUBJECTS: 73 male patients attending for treatment of sexually
      transmitted diseases, including 14 patients with genital warts which did not
      involve the urethral meatus. METHODS: Urinary sediment was tested for HPV DNA and
      human beta globin gene DNA by PCR methodology. A consensus primer set capable of
      detecting a wide range of HPV types was used. PCR product was analysed by gel
      electrophoresis and ethidium bromide staining. RESULTS: HPV DNA was not detected
      in any of the specimens. Human beta globin gene DNA was identified in 40 of the
      73 specimens (55%). CONCLUSIONS: Screening urinary sediment for HPV DNA by PCR
      methodology with analysis of PCR product by gel electrophoresis and ethidium
      bromide staining is probably unhelpful for studying the prevalence of urethral
      HPV infection in men.

PMID- 7721289
TI  - The importance of different components of normal human serum and lysozyme in the
      rapid immobilisation of purified Treponema pallidum, Nichols strain.
AB  - OBJECTIVES: To study the role of different components in normal human serum and
      the role of lysozyme in rapid immobilisation of Percoll purified T pallidum
      (Nichols). MATERIALS AND METHODS: The immobilisation of Percoll purified T
      pallidum was studied after pre-incubations with different serum fractions (Fr) of
      normal human serum (Fr 1, containing IgM; Fr 2, containing IgG and a low level of
      haemolytic complement, and Fr 1 (abs), depleted of IgG). A guinea-pig serum pool
      was used as a complement source in the immobilisation experiments. The influence
      was studied of removal of lysozyme from guinea-pig serum on the immobilisation
      reactions. Further experiments were performed, using a fluorescence technique, to
      detect C3b depositions on fixed treponemes and treponemes in suspension. RESULTS:
      Rapid immobilisation of Percoll-purified treponemes by the NHS serum fractions
      occurred only after preincubation with Fr 1 and Fr 2 simultaneously. This was
      largely dependent on the presence of a small amount of haemolytic C in Fr 2.
      Removal of lysozyme reduced this rapid rate of immobilisation. In fluorescence
      experiments it was demonstrated that C3b deposition on fixed (that is damaged)
      treponemes occurred upon their incubation with Fr 2 or the combination of Fr 1
      and 2. However, on treponemes in suspension C3b deposition occurred only after
      incubation with the combination of Fr 1 and 2. CONCLUSION: The rapid
      immobilisation of Percoll purified treponemes by serum fractions from normal
      human serum requires antibodies of the IgM and IgG class, together with
      complement and lysozyme. Omission of one of these reactants slows immobilisation.
      Our experiments suggest that the reactants act in sequence: the loss of integrity
      of the outer membrane by an attack by IgM and C offers the opportunity for
      lysozyme to hydrolyse the peptidoglycan layer surrounding the cytoplasmic
      membrane of the treponemes, which then is accessible for attack by antibodies and
      C.

PMID- 7721290
TI  - Neisseria gonorrhoeae isolated at St. Mary's Hospital London, 1980-91.
AB  - OBJECTIVE: To describe and discuss the trends in the isolation of Neisseria
      gonorrhoeae from patients attending the Genitourinary Medicine Clinic at St.
      Mary's Hospital, Paddington, London between 1980 and 1991. DESIGN: A
      retrospective study of the total number of gonococci isolated over an eleven year
      period was performed. In addition, for the years 1988-1991 the number of isolates
      from homosexual men was analysed by age of the patient, site of infection and HIV
      antibody status of the patient. RESULTS: The total number of N. gonorrhoeae
      isolates identified declined markedly between 1980 and 1989 from 3670 to 750
      isolates. Over the same time period the number of specimens screened for N.
      gonorrhoeae fell by 50%. In 1990 there was an increase in N. gonorrhoeae isolates
      but this was not maintained, and in 1991 the number of N. gonorrhoeae fell to its
      lowest level of 638 isolates. The decrease since 1980 occurred in both men and
      women although the number of rectal isolates from men showed a steeper decline
      reaching its lowest level of 24 isolates in 1988. The number of rectal isolates
      from homosexual men has since increased with a peak in 1990. Many of the
      infections among homosexual men occurred in older men and included insignificant
      number of patients who were HIV positive. CONCLUSION: Gonorrhoea among attenders
      at St. Mary's Hospital has declined dramatically since 1980 following trends
      reported from much of Europe. The increase in gonococcal isolates since 1989 and
      the peak in 1990 are unexplained but are coincident with a higher number of
      isolates from homosexual men.

PMID- 7721291
TI  - Sensitive detection and typing of Chlamydia trachomatis using nested polymerase
      chain reaction.
AB  - OBJECTIVES: A method based on a nested polymerase chain reaction (PCR) was
      developed to detect and to type Chlamydia trachomatis from low titre samples by
      amplifying a large portion of the major outer membrane protein gene. The
      sensitivity of this procedure was evaluated in urogenital clinical samples in
      comparison with culture. SPECIMENS: A series of 787 urogenital specimens,
      including 37 (4.7%) positive by culture, together with 227 other samples that had
      been found to yield less than 25 chlamydial inclusions in culture were tested.
      METHODS: Samples were pelleted, resuspended in 1 mM NaOH, heated and amplified
      without further purification. After 40 cycles of PCR, 1 microliters of product
      was amplified by a further 30 cycles of PCR using a second set of primers nested
      within the initial pair. Positives were detected by agarose gel electrophoresis
      and confirmed by repeating the PCR analyses and determining the serovar of both
      amplified samples by restriction fragment length polymorphism. RESULTS: Nested
      PCR allowed detection of 96% and culture 77% of positives with only three samples
      repeatedly positive by PCR but considered false positives because a different
      serovar was identified in the two amplifications. Of culture-positive samples
      with less than 11 chlamydia inclusion-forming-units 97% could be detected by
      nested PCR and most still gave a positive signal when diluted hundred fold.
      CONCLUSIONS: Nested PCR provided the basis for a very sensitive C trachomatis
      detection and typing strategy. Repetition and typing positive samples facilitated
      detection of false-positive PCR specimens resulting from contamination of the PCR
      process or any reagent except the original sample.

PMID- 7721292
TI  - Is endometrial infection with Candida albicans a cause of recurrent vaginal
      thrush?
AB  - OBJECTIVE: It was hypothesised that the endometrium might act as a reservoir for
      candida, thus infecting the vagina as the endometrium is shed during
      menstruation. DESIGN: A prospective study of women with recurrent vulvo-vaginal
      candidiasis. The endometrium was sampled and cultured for candida species.
      SETTING: Central London STD clinic. SUBJECTS: 26 women were enrolled, of whom 20
      completed the study. RESULTS: One patient had a positive endometrial culture for
      candida species, the isolate being Candida krusei. CONCLUSIONS: The endometrium
      is not a common resevoir for candida species and therefore, infection at this
      site is an unlikely cause of recurrent vaginal candidiasis.

PMID- 7721293
TI  - Soap and water prophylaxis for limiting genital ulcer disease and HIV-1 infection
      in men in sub-Saharan Africa.
AB  - In general, East, Central and Southern Africa appear to be worse affected by HIV
      1 infection than West Africa. So far there is little evidence to suggest that
      differences in either sexual behaviour or numbers of sexual partners could
      account for this disparity. Two risk factors in men for acquiring HIV-1, that
      tend to vary along this geographical divide, are lack of circumcision and genital
      ulcer disease (GUD) which are much less common in West Africa. Although
      uncircumcised men with GUD are an important high frequency HIV-1 transmitter core
      group, few interventions have targeted such individuals. Given the recent
      expansion in AIDS-related technologies, is it possible that methods effective in
      limiting GUD in the preantibiotic era have been overlooked? During the first and
      second world wars, chancroid, the commonest cause of GUD in Africa today, was
      controlled successfully with various prophylactics including soap and water. Many
      parts of Africa are undergoing social upheaval against a background of violence,
      and in this environment soap and water prophylaxis would now seem to merit re
      evaluation as an intervention for preventing both GUD and HIV-1 in uncircumcised
      men. By facilitating healing of traumatic, inflammatory and infected penile
      lesions, pre- and post-exposure prophylaxis with soap and water could be a cheap
      and effective method for decreasing the risks of acquiring GUD and HIV in this
      vulnerable group of uncircumcised men.

PMID- 7721294
TI  - Cutaneous vasculitis presenting on the penis.
AB  - Cutaneous vasculitis is frequently located on the lower limbs. We describe a
      patient who developed palpable purpura affecting the penis as the presenting sign
      of more widespread lesions of Henoch-Schonlein purpura.

PMID- 7721296
TI  - Tissue erosion with perianal warts in HIV infection.
AB  - A case of painful tissue erosion due to perianal warts is described with HIV
      infection. Such a development can be avoided by frequent and careful monitoring.

PMID- 7721295
TI  - Sexually transmitted diseases in children: herpes simplex virus infection,
      cytomegalovirus infection, hepatitis B virus infection and molluscum contagiosum.

PMID- 7721297
TI  - "The Cinderella of medicine": sexually-transmitted diseases in Britain in the
      nineteenth and twentieth centuries.

PMID- 7721299
TI  - Transmission of gonorrhoea through an inflatable doll.

PMID- 7721298
TI  - Risk for hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
      infections among prostitutes.

PMID- 7721300
TI  - Analysis of failed appointments in a genitourinary department in the West
      Midlands of the UK.

PMID- 7721301
TI  - Carcinoma of the vulva and asymptomatic lichen sclerosus.

PMID- 7721302
TI  - Staphylococcus aureus pericarditis in a patient with AIDS.

PMID- 7721303
TI  - Fournier's gangrene and HIV disease.

PMID- 7721304
TI  - The rhetoric of nursing theory.
AB  - Skeptics who question the validity and relevance of nursing theory in the nursing
      curriculum demonstrate the failure to persuade nurses of the importance of
      theory. Attempts to justify theory by forcing its use in contexts where it barely
      fits have contributed to the increasing disenchantment. But however misused and
      misunderstood, theory is nevertheless a lasting and essential part of nursing
      knowledge. Theory is the intellectual life of nursing. To further research,
      experiment, and insight in nursing as a discipline, theorizing must be encouraged
      -subject as all intellectual efforts must be--to honest critique and a healthy
      willingness to acknowledge success or failure.

PMID- 7721305
TI  - Clinical features and psychosocial factors in young adults with genital herpes.
AB  - Clinical features of genital herpes, perceived causes, stress symptoms,
      treatments, and psychosocial factors in 70 young adults as compared to normative
      data for non-patient controls are described. The clinical features of the disease
      were congruent with those of other groups studied. Stress was viewed as the major
      cause of recurrence, headaches the major stress symptom, and acyclovir (an
      antiviral drug), was the major treatment. Statistically significant differences
      were found between scores obtained from the sample of young adults with genital
      herpes on three of four standardized psychological instruments when compared with
      normative data for non patient controls. Young adults with genital herpes had a
      lower self concept, more psychopathology, a greater frequency of daily hassles,
      and less intensity of uplifts. No differences were found, however, between the
      two groups in scores on depression.

PMID- 7721306
TI  - Art, aesthetics, science, nursing.

PMID- 7721307
TI  - Functional performance in people with chronic obstructive pulmonary disease.
AB  - The extent to which individuals with a chronic physical illness perform their day
      to-day activities and maintain the independence and autonomy they desire is both
      an indicator of adaptation and an important clinical outcome criterion. Yet the
      concept of functional performance is not well understood. Studies of people with
      chronic obstructive pulmonary disease (COPD) have attempted to identify
      physiologic and psychosocial factors that contribute to functioning in this
      population. These studies have used a melange of terms, including functional
      status, functional ability, quality of life, and health status interchangeably.
      They have also employed a variety of instruments to operationalize functional
      performance and an assortment of predictors to understand the phenomena. Perhaps
      as a result of this disarray, no attempt has been made to synthesize the
      literature for nursing research and practice. The purpose of this paper is to
      summarize the research on functional performance in people with COPD, indicate
      areas of understanding and quandary, suggest possible flaws, and propose several
      new directions for practice and research.

PMID- 7721308
TI  - Smoking behaviors of women after diagnosis with lung cancer.
AB  - The purpose of this study was to describe the smoking behavior of women with a
      recent diagnosis or recurrence of lung cancer. A convenience sample of women (N =
      65) participated in interviews about their smoking status, their perception of
      the effect of their diagnosis on the smoking behaviors of others, and self
      reports of symptom distress and functional status. Content analysis of the
      audiotapes was used to classify responses. Exemplars describe feelings related to
      smoking, smoking cessation, and responses of others. Current smokers were likely
      to be younger (F4.60 = 4.3, p < .05). In this small sample, symptom distress and
      functional status were not statistically differentiated by smoking status;
      current smokers had the greatest mean distress from cough. Diagnosis had a
      variable effect on the smoking behavior of family members with over 25% stopping
      smoking in response to the diagnosis; 31% of smoking spouses continued to smoke.

PMID- 7721309
TI  - Kudos to Dr. dela Cruz.

PMID- 7721310
TI  - Prevent AIDS.

PMID- 7721311
TI  - Women and AIDS.

PMID- 7721312
TI  - The black box of patient outcomes research.

PMID- 7721313
TI  - Validation and coding of the NIC taxonomy structure. Iowa Intervention Project.
      Nursing Interventions Classification.
AB  - Processes for validation and coding of the taxonomy for the Nursing Interventions
      Classification (NIC) are described. A sample of nurses expert in theory
      development rated the NIC taxonomy using five criteria. Following identification
      of a stable structure, the taxonomy was coded with each intervention receiving a
      unique number. A coded and valid taxonomic structure facilitates use of the
      classification in computerization and makes possible the collection of comparable
      data. A coded classification can also be used in reimbursement systems.

PMID- 7721314
TI  - Model for clinical teaching ... a should.

PMID- 7721315
TI  - Phenomenology as method.

PMID- 7721316
TI  - Valuable opinions of nursing staff.

PMID- 7721317
TI  - Duplicate publication in the nursing literature.
AB  - The purpose of this study was to identify examples of duplicate publication in
      the nursing literature and determine what types of duplicate articles are
      published. From the sample of 642 articles published by 77 authors during a 5
      year period, 181 articles were classified as duplicate. Forty-one authors
      published at least one form of duplicate article. Fifty-nine duplicate articles
      did not reference the primary article. Duplicate publication itself is not
      unethical, but duplicate publication without referencing duplicate work is
      unethical and may violate copyright law.

PMID- 7721318
TI  - Duplicate publication: guidelines for nurse authors and editors.

PMID- 7721319
TI  - Case report: dystonia.
AB  - Following a motor vehicle accident, Ms. G.'s head began intermittently pulling to
      the right. Within 6 months, the pulling worsened, leaving her head painfully
      fixated, touching her right shoulder. She was hospitalized for evaluation and
      numerous drugs were used but unsuccessfully. Baffled, her physician ordered a
      psychiatric consult. Hysterical conversion reaction was the resultant diagnosis.
      Ms. G. was treated with thioridazine and chlorpromazine, and psychotherapy was
      recommended.

PMID- 7721320
TI  - Where are monthly research journals?

PMID- 7721321
TI  - Voices from different places: but why a medical school faculty?
AB  - Interdisciplinary collaboration between nursing and medicine is a valued goal,
      but one which is difficult to achieve. Two nurses who are faculty members in
      medical schools reflect on their unique roles and how these encompass
      interdisciplinary research, teaching, and practice.

PMID- 7721322
TI  - Conflict of interest in academia.
AB  - Conflict of interest in academia has been increasingly recognized over the past
      decade. Yet, comparatively little is written in respect to this problem. The
      authors provide an overview of conflict of interest as it applies to nursing
      research and addresses how it can also affect practice and education. Resources
      for the development of guidelines to prevent conflicts of interest are presented.

PMID- 7721323
TI  - A Fulbright in Sweden: runes, academics, archetypal motifs, and other things.

PMID- 7721324
TI  - Equal team partners? The roles of principal investigators, co-principal
      investigators and co-investigators on federally supported research grants.
AB  - A survey of 188 NLN-accredited graduate nursing programs was done to determine
      how the research roles of principal investigator (PI), co-principal investigator
      (Co-PI) and co-investigator (Co-I) are supported and to examine the similarities
      and differences in benefits for PIs, Co-PIs and Co-Is. Most schools did not
      provide salary supplementation in addition to the usual salary for any
      investigators. For other benefits, the PI was more likely than was the Co-PI or
      Co-I to receive direct access to indirect cost recovery dollars, the use of extra
      research assistants, and the reduction of teaching time commensurate with the
      time supported by their grant. If the team approach is truly valued, should not
      all investigators be rewarded in a like manner?

PMID- 7721325
TI  - Nightingale's spiritual philosophy and its significance for modern nursing.
AB  - In her manuscript, Suggestions for Thought, Nightingale attempted to integrate
      science and mysticism. She wrote that the universe is the incarnation of a divine
      intelligence that regulates all things through law. For Nightingale, the laws of
      science are the "Thoughts of God." Because of her deep conviction about universal
      law, she did not believe in miraculous intervention as an answer to prayer. Human
      beings must discover the laws of God and apply them for health and wholeness.
      Prayer is attuning or joining one's personal self with the consciousness of God,
      which is found in the deepest recesses of one's own being. Nightingale's idea of
      spirituality as intrinsic to human nature and compatible with science can guide
      the development of future nursing practice and inquiry.

PMID- 7721326
TI  - Roles of beta-galactosidase of B lymphocytes and sialidase of T lymphocytes in
      inflammation-primed activation of macrophages.
AB  - The outer surface of mouse B lymphocytes carries constitutive and inducible beta
      galactosidase isozymes. A brief (30 min) treatment of B lymphocytes with
      lysophosphatidylcholine (lyso-Pc) immediately induced an approximate 3-fold
      higher beta-galactosidase activity than the constitutive isozyme of untreated B
      lymphocytes. Thus, the lyso-Pc-inducible isozyme is not a de novo enzyme. Outer
      surface of mouse T lymphocytes carries constitutive (non-Neu-1) and inducible
      (Neu-1) sialidase isozymes. The lyso-Pc-inducible beta-galactosidase of B
      lymphocytes and the Neu-1 sialidase of T lymphocytes were required for conversion
      of vitamin D3-binding protein (Gc protein) to a potent macrophage activating
      factor. This enzymatic generation of the macrophage activating factor was
      mediated via enzyme-associated receptors.

PMID- 7721327
TI  - Large increase in thermal stability of the CH2 domain of rabbit IgG after acid
      treatment as evidenced by differential scanning calorimetry.
AB  - Rabbit IgG after exposure to 0.05 M glycine-HCl, pH 2.0, and native IgG were
      compared by differential scanning calorimetry (DSC) at pH 3.5 and C1q binding
      studies at pH 7.8. For acid-treated IgG, a large increase (by approx. 12-15
      degrees C) in thermal stability of the CH2 domain occurs and this domain no
      longer demonstrates a separate and thermodynamically independent unfolding at 56
      degrees C seen for native IgG. The results suggest that stabilization of the CH2
      domain in acid-treated IgG arises from stronger, relative to the native protein,
      interaction of the CH2 domain with adjacent and more stable IgG domain(s).
      Conformational differences of the two forms of IgG were confirmed at neutral pH
      by a 4-fold increase of C1q-binding affinity of acid-treated IgG.

PMID- 7721328
TI  - Restoration of murine cytomegalovirus (MCMV) induced myelosuppression by AS101.
AB  - Infection with cytomegalovirus (CMV) continues to be one of the most common
      complications following allogeneic bone marrow transplantation. The gravest
      danger for the host occurs when the virus is reactivated as a result of
      immunosuppression. In this report we studied the effects of sublethal murine
      cytomegalovirus (MCMV) infection on the hemopoietic system including bone marrow
      (BM) cellularity, production of colony stimulating factor (CSF) and interleukin-6
      (IL-6) and the development of granulocyte-macrophage colony forming units (CFU
      GM), and BM stromal cell viability. Our findings show that the virus infection
      led to a significant decrease in the number of BM cells and in the production
      levels of CSF and IL-6. There was also a decrease in the number of stromal cells,
      as reflected by the number of colony forming unit fibroblasts (CFU-F), and in the
      relative number of CFU-GM progenitors. Treatment of MCMV infected mice with the
      immunomodulator AS101 [ammonium trichloro (dioxyethylene 0-0')tellurate] restored
      significantly CSF and IL-6 production by BM cells to levels of uninfected control
      mice as well as the number of CFU-F and stromal cell elements which consequently
      led to the restoration of the total number of BM cells. Results presented here
      indicate that AS101 may have immunomodulatory effects on MCMV mediated
      myelosuppression. Administration of AS101 to patients with CMV associated BM
      damage may improve the restoration of their BM function.

PMID- 7721329
TI  - Characterization of the GTP/GDP binding site in the murine CD3-zeta polypeptide
      chain.
AB  - Using a newly developed in situ affinity-labeling method of nucleotide-binding
      proteins (NTPoxi technique) we discovered that the human T-cell receptor
      associated CD3-zeta protein might bind GTP/GDP. To further characterize GTP/GDP
      binding to CD3-zeta, murine T-cell lines expressing zeta zeta homodimers or CD3
      zeta/Fc epsilon R1 gamma heterodimers were used. Specific GTPoxi labeling of CD3
      zeta was found in all murine T cells in which a complete CD3-zeta polypeptide
      chain was expressed, including cells in which CD3-zeta was disulfide bridged to
      the Fc epsilon R1 gamma chain. In murine T cells the kinetics of labeling of CD3
      zeta was similar to that of small G-proteins. Upon activation of murine T cells a
      slight but significant increase in GTPoxi labeling of CD3-zeta was detected.
      Whether all 3 so-called 'Reth motifs' (zeta A, zeta B and/or zeta C) were
      necessary for the binding of GTP/GDP was addressed by using cells expressing
      truncated CD3-zeta molecules. Whereas truncated CD3-zeta, in which zeta A and
      part of zeta B were deleted, was still able to bind GTP, upon deletion of all 3
      Reth motifs cross-linking by the GTPoxi method became impossible. Regardless of
      whether this implies a direct or indirect binding of GTP/GDP to CD3-zeta, these
      nucleotides and their hydrolysis must play an important role in T-cell activation
      through the TCR/CD3 complex.

PMID- 7721330
TI  - Disparity in the percentage of CD4+ T lymphocytes and prognosis of HIV-infected
      intravenous drug users in Malaysia.
AB  - The CD4+ T-lymphocyte absolute count (CD4ac), CD4+ T-lymphocyte percentage (CD4%)
      and total lymphocyte count (Loac) were assessed in HIV-seropositive intravenous
      drug users (IVDU) with reference to their correlation with the clinical
      categories A, B, and C as stipulated by the Centre of Disease Control and
      Prevention, USA (CDC) and with each other. It was found that while the CD4ac and
      Loac correlated with the clinical categories, CD4% did not. This may suggest that
      in our local setting, the CD4% may not necessarily be a suitable alternative
      marker to CD4ac as proposed by CDC. Furthermore, the CD4% of the normal subjects
      in this study was found to be relatively lower than the reported Caucasian
      levels. This may indicate that the use of the cut-off level of less than 14% as
      an AIDS-defining criteria may not be applicable for our HIV-seropositive IVDU. In
      addition, unlike the CD4ac which correlated directly with CD4% and Loac, the CD4%
      did not correlate with Loac. Therefore, due to the observed disparity with
      clinical status of patients and its possibly lower levels in our normal
      population, CD4% as a marker for staging HIV disease should be used with caution
      in our setting. Such findings may also have an impact on the use of established
      markers for the monitoring and classification of HIV-infected individuals in this
      region.

PMID- 7721332
TI  - Conversion of human fibroblasts to tissue macrophages by the Snyder-Theilen
      feline sarcoma virus (ST:FeSV(FeLV)): productive infection by Leishmania major.
AB  - The decisive role of macrophages in T-cell differentiation is best exemplified by
      cutaneous leishmaniasis. During infection, Leishmania attach to macrophages, the
      only site of replication for the parasite. We have recently demonstrated the
      conversion of human fibroblasts to tissue macrophages (TM) by transduction with
      the Snyder-Theilen feline sarcoma virus (ST:FeSV-(FeLV)). Since Leishmania have
      tropism only for macrophages, we have used the parasite to ascertain the
      functional phenotype of the ST:FeSV-induced TM. Here, we have demonstrated the
      productive infection of the ST:FeSV-induced TM by L. major. These results point
      to the utility of ST:FeSV-induced TM in studies that concern the role of human
      macrophages in T-cell differentiation during the course of infection by
      Leishmania.

PMID- 7721331
TI  - Both cathepsin B and cathepsin D are necessary for processing of ovalbumin as
      well as for degradation of class II MHC invariant chain.
AB  - The effect of highly selective inhibitors of cathepsins on the processing of
      ovalbumin (OVA) and the presentation of an OVA-derived antigenic peptide (OVA323
      339) by antigen presenting cells (APC) was investigated. Both CA-074 (a specific
      inhibitor of cathepsin B) and pepstatin A (a specific inhibitor of cathepsin D)
      showed an inhibitory effect on the IL-2 production from an OVA-specific, I-Ad
      restricted helper T (Th) cell clone upon stimulation with OVA presented by the I
      Ad-positive APC. In contrast, the presentation of the antigenic epitope, OVA323
      339, to the same Th clone was not inhibited by either CA-074 or pepstatin A
      alone, nor even by the mixture of both inhibitors. When APC were treated with
      cathepsin inhibitor for 24 h, and then antigen and Th were added to the culture,
      the presentation of not only OVA but also an OVA-derived antigenic peptide was
      inhibited by either cathepsin inhibitor alone. In addition, the expression of
      invariant chain on APC was significantly augmented by the pretreatment of APC
      with either cathepsin inhibitor. Two main conclusions are drawn from these
      results. First, not only aspartyl protease, such as cathepsin D, but also thiol
      protease, such as cathepsin B, is involved in antigen processing by APC. Second,
      both cathepsin B and cathepsin D are necessary for degradation of the invariant
      chain (Ii) from the MHC class II alpha beta heterodimer in endosomes in order to
      express functional MHC class II molecules for binding antigenic peptides.

PMID- 7721333
TI  - Influence of transforming growth factor-beta (TGF-beta) on the immunoglobulin
      production by EBV-infected B cell cultures.
AB  - TGF-beta inhibits the proliferation of human B lymphocytes stimulated by a
      variety of activators, including EBV. However, EBV-immortalised cells are
      refractory to TGF-beta. The influence of TGF-beta on B cell maturation varies,
      apparently depending on the origin of the B lymphocytes and their
      maturation/activation state, the strength of the stimulus and the presence of
      cofactors. We investigated the effect of TGF-beta on immunoglobulin production by
      5-day-old EBV-infected B cells. TGF-beta added at the initiation of the cultures
      inhibited IgM, IgG and IgA secretion by decreasing the numbers of secretory
      cells. The inhibition of IgM secretion was strongest. At the cytoplasmic level,
      TGF-beta reduced the expression of IgM heavy, lambda and kappa light chains but
      not IgG and IgA heavy chains. However, the IgM production by an established EBV
      transformed B cell line was not affected by TGF-beta. Thus, TGF-beta inhibited
      EBV-induced maturation of the B cells until they acquired a transformed state. We
      discuss the relevance of these findings for the potential role of TGF-beta on EBV
      infection.

PMID- 7721334
TI  - Ontogeny of interferon alpha secreting cells in the porcine fetal hematopoietic
      organs.
AB  - We examined the ontogeny of IFN-alpha Secreting Cells (IFN-alpha SC) in different
      hematopoietic organs and blood of porcine fetuses at different stages of
      gestation. Cells were induced to produce IFN-alpha by incubation with the
      coronavirus TGEV and IFN-alpha SC were detected by ELISPOT. A striking finding
      was that IFN-alpha SC could be detected in the fetal liver as early as at 26 days
      of gestation, i.e., during the first quarter of gestation, a period at which T
      cell markers could not be detected by flow cytometry. In addition, IFN-alpha SC
      could be detected in the cord blood, the spleen and the bone marrow of fetuses at
      later stages of gestation. These data indicate that IFN-alpha SC appear very
      early during the ontogeny of the immune system, long before the development of
      the specific immune system, and may therefore represent an early antiviral
      defence mechanism. IFN-alpha SC were found to be associated with hematopoietic
      organs, which argues for their hematopoietic lineage.

PMID- 7721335
TI  - Thiol supplier N-acetylcysteine enhances conjugate formation between natural
      killer cells and K562 or U937 targets but increases the lytic function only
      against the latter.
AB  - In this in vitro study, an evaluation of the importance of intracellular
      oxidative balance on cell-mediated cytotoxicity was performed by analyzing the
      effects of the antioxidant N-acetylcysteine (NAC), a specific thiol supplier, on
      natural killer (NK) cell-mediated cytotoxicity. The results obtained indicate
      that an enhancement of target cell (TC) killing can be detected when a pre
      exposure of effector cells (EC) to NAC was performed. However, this effect seems
      to depend upon the TC type used. In fact, the increase of EC activity was
      detected against the differentiated U937 TC while no changes were detected by the
      same effectors against K562 cells. The mechanism of this enhancement seems to be
      ascribable to an increased ability of NAC-exposed NK cells to form conjugates
      (binding) which, in turn, appears to be due to a specific effect of NAC on actin
      microfilaments. A role for NAC as a cytoskeleton thiol-modifier contributing to
      the activation of effector cells can thus be hypothesized.

PMID- 7721336
TI  - Subcellular localization and characterization of interleukin-1 alpha produced by
      rat bladder cancer cells.
AB  - A rat bladder cancer cell line BC31ad, previously reported to constitutively
      release tumor necrosis factor alpha (TNF alpha), was found to produce an
      interleukin (IL)-1-like factor inducing proliferation of murine thymocytes in a
      standard costimulation assay (LAF activity). IL-1-like factor was partially
      purified by DEAE-Sephacel, Sephacryl S-200 and MonoQ-FPLC chromatographies from
      the serum-free conditioned medium of a BC31 adderived clone, C19, to the specific
      activity of 3.2 x 10(6) U/mg and characterized as a protein of molecular weight
      17 kDa with isoelectric point 5.2. LAF activity of IL-1-like factor was
      specifically neutralized with anti-rat IL-1 alpha but not with anti-rat IL-1
      beta. These findings show that the IL-1-like factor is rat IL-1 alpha, although
      the precise molecular relationship with monocyte IL-1 alpha is unclear.
      Furthermore, IL-1 alpha was shown to be primarily located in the cytosol and
      plasma membrane without spontaneous release. A kinetics study indicated that it
      was leaked into the medium late in culture resulting from cell destruction, in
      contrast to TNF alpha which was released as the cell number was increased. We
      discussed the possible role of IL-1 alpha as an autocrine or paracrine growth
      regulator.

PMID- 7721337
TI  - Tumour necrosis factor-alpha induces preferential expression of stress proteins
      in virulent promastigotes of Leishmania donovani.
AB  - Intracellular replication of Leishmania donovani inside macrophages is essential
      for production of disease and development of the parasite. Tumour necrosis factor
      alpha (TNF) plays an integral role in host response to Leishmania. The effect of
      TNF on expression of heat-shock proteins (Hsp) was examined in promastigotes of
      L. donovani. TNF treatment led to an increased expression of Hsp83, Hsp70 and
      Hsp65 in virulent, but not avirulent, parasites. In response to stress by H2O2 or
      sodium arsenite, an increased expression of Hsp60 was observed in the virulent,
      but not avirulent, parasites. The virulent promastigotes were found to be more
      resistant to the toxic effects of TNF and other stresses. The data indicated that
      Hsp expressed in response to stress encountered in macrophages may confer
      protection to parasites and play a crucial role in their survival in the
      mammalian host.

PMID- 7721338
TI  - An adjuvant formulation based on N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D
      isoglutamine with dimethyldioctadecylammonium chloride and zinc-L-proline complex
      as synergists.
AB  - The formulation consists of N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D
      isoglutamine, dimethyldioctadecylammonium chloride and the trace element zinc as
      an L-proline complex. This ternary synergistic composition shows promise as a new
      adjuvant.

PMID- 7721339
TI  - Molecular characterization of a human anti-HIV 1 monoclonal antibody revealed a
      CD26-related motif in CDR2.
AB  - Genes encoding the immunoglobulin variable regions of a human anti-HIV-1 IgG1
      kappa monoclonal antibody were rescued from a hybridoma, derived from a sero
      negative donor, using PCR cloning and expression in Escherichia coli. The ELISA
      binding results obtained from the expressed Fab fragment confirmed the anti-V3
      loop specificity for HIV-1 (LAI) of the original antibody. In addition, an amino
      acid sequence derived from the second complementarity determining region (CDRH2)
      of the heavy chain was found to be very similar to the catalytic motif of CD26, a
      T-cell activation antigen. Furthermore, synthetic peptides containing both the
      catalytic domain of CD26 and CDRH2 of the antibody showed specific binding to an
      HIV peptide representing the V3 region in a dose-dependent manner. This suggests
      an involvement of CD26 as a possible coreceptor for HIV-1.

PMID- 7721340
TI  - The interactions of anti-MLI monoclonal antibodies with isoforms of the lectin
      from Viscum album.
AB  - Monoclonal antibodies (mAb) reacting with native (TA5, TB12) and denatured (T33,
      T35) plant toxin mistletoe lectin I (MLI) from Viscum album have been obtained.
      The interaction between mAbs and native toxin with ML isoforms (MLII, MLIII) has
      been investigated. An immunological cross-reaction has been shown to take place
      for mAb TA5 (anti-A-chain of MLI) between MLII and MLIII isoforms of toxin. TA5
      has not inhibited enzyme activity of the A-chain in a rabbit reticulocyte cell
      free system. TB12 has been shown to react with the galactose-binding site of the
      B-chain. TA5 and TB12 have shown no cross-reaction with plant toxin ricin. The
      association constants for mAbs have been determined. The nature of heterogeneity
      of the lectins from Viscum album is discussed.

PMID- 7721341
TI  - Tumor-associated glycoantigen, sialyl Lewis(a) as a target for bispecific
      antibody-directed adoptive tumor immunotherapy.
AB  - The KM231 mAb recognizing sialyl Lewis(a) (sLe(a)) epitope of glycoprotein or
      glycolipid expressed on various human cancers was used to prepare bispecific
      antibody (BSAb) containing anti-CD3 x anti-sLe(a) mAb. The effect of anti-CD3 x
      anti-sLe(a) BSAb on the induction of cytotoxicity by activated T cells was
      investigated. The activated CD3+ T cells expressing CD8 or CD4 were induced from
      human peripheral blood mononuclear cells by culture with recombinant IL-2 plus
      immobilized anti-CD3 mAb. The activated CD8+ and CD4+ T cells showed marginal
      cytotoxicity against tumor cells by themselves. However, addition of anti-CD3 x
      anti-sLe(a) BSAb resulted in a great augmentation of their cytotoxicity against
      gastrointestinal tumor cells. The BSAb also triggered IL-2 production of CD4+
      helper/killer T cells during lysis of tumor cells. Moreover, the BSAb was
      demonstrated to have a potent in vivo antitumor activity against human colon
      cancer implanted in nude mice by combination with CD4+ helper/killer cells. These
      results demonstrated that sLe(a) antigen might be a good target molecule for BSAb
      directed adoptive tumor immunotherapy.

PMID- 7721342
TI  - The enhancement of growth of a syngeneic plasmacytoma in BALB/c mice by pristane
      priming is not due to immunosuppressive effects on antibody-forming cell or
      mitogen-responsive splenocytes.
AB  - The effects of pristane on some immunity parameters in BALB/c mice were studied.
      The intraperitoneal administration of a single dose of pristane induced a strong
      inflammatory reaction that lasted longer than 10 days. When mice were immunized
      with sheep erythrocytes 10 days after pristane administration, the response of
      hemolytic IgM-forming cells was increased and that of hemolytic IgG-forming cells
      was decreased; however, the total number of antibody-forming cells did not
      change. The proliferative response of splenocytes to concanavalin A was increased
      in mice that received pristane 10 days earlier. Development of the syngeneic NS1
      plasmacytoma was enhanced by administration of pristane 2 days or 10 days before
      tumor transplantation. We concluded that enhancement of plasmacytoma development
      was not due to immunosuppressive properties of pristane but to other factors such
      as ascites induction.

PMID- 7721343
TI  - Killing of intrafamilial leukocytes by earthworm effector cells.
AB  - When Lumbricus and Eisenia coelomocytes are cultured together in intrafamilial
      xenogeneic combinations, significant cytotoxicity occurs at 24 h but not at 5 nor
      72 h, as shown by trypan blue assay. In a 4.5-h assay, measuring 51Cr release,
      using an effector/target ratio of 25:1, unpooled cells from a single Lumbricus
      killed Eisenia cells at levels of 6% and 14%. However, Eisenia coelomocyte
      survival was high and identical in either cell-free xenogeneic (Lumbricus)
      coelomic fluid or in artificial medium. In this 1-way assay, earthworm
      (Lumbricus) coelomocytes act as effector cells that kill non-self target cells,
      even those of other earthworms. Comparisons with previous results reveal greater
      reliability and consistently repeatable results when the 51Cr release assay is
      used to measure cytotoxicity regardless of the targets.

PMID- 7721344
TI  - Modulation of monocyte antigen-presenting capacity by tumour necrosis factor
      alpha (TNF): opposing effects of exogenous TNF before and after an antigen pulse
      and the role of TNF gene activation in monocytes.
AB  - We have previously shown that exogenous human recombinant tumour necrosis factor
      alpha (rTNF), added before an antigen pulse, enhanced antigen presentation by
      human blood monocytes. The present study shows that, surprisingly, rTNF added
      after an antigen (PPD) pulse inhibited, while anti-TNF monoclonal antibody (mAb)
      enhanced, antigen presentation. mAbs htr-9 against p55 TNF receptor type I (TNF
      RI) abrogated rTNF enhancing effect on PPD presentation and decreased presenting
      activity of untreated monocytes while utr-1 mAb, against p75 TNF receptor type II
      (TNF-RII), reversed the inhibitory effect of rTNF given after antigen pulse. PPD
      and rTNF when added singly induced TNF-mRNA accumulation in monocytes.
      Pretreatment of monocytes with rTNF followed by a PPD pulse caused an enhancement
      of TNF-mRNA accumulation. However, when post-treatment with rTNF was applied to
      PPD-pulsed monocytes, then inhibition of TNF gene expression was seen. This may
      point to the role of endogenously generated TNF in regulation of antigen
      presenting capacity of monocytes. These studies indicate that TNF is an important
      regulator of monocyte antigen-presenting capacity and that the level of TNF gene
      activation in monocytes may be associated with their ability to present nominal
      antigen.

PMID- 7721345
TI  - Glycyrrhizin (20 beta-carboxy-11-oxo-30-norolean-12-en-3 beta-yl-2-O-beta-D
      glucopyranuronosyl-alpha-D-glucopyranosiduronic acid) improves the resistance of
      thermally injured mice to opportunistic infection of herpes simplex virus type 1.
AB  - The effect of glycyrrhizin (GR) on the resistance of thermally injured mice to
      opportunistic herpes simplex virus type 1 (HSV) infection was investigated. We
      have previously reported that the susceptibility of thermally injured mice or
      normal mice inoculated with T6S cells (a clone of burn-associated CD8+ CD11b+ TCR
      gamma/delta + type-2 suppressor T cells), to HSV infection was about 100 times
      greater than it was in normal mice. When thermally injured mice were treated i.p.
      with a 10 mg/kg dose of GR 2 and 4 days after infection of HSV, the resistance of
      these mice to HSV was improved to levels observed in normal mice. The adoptive
      transfer of splenic mononuclear cells (MNC) from normal mice treated with GR (GR
      MNC) to thermally injured mice (recipients) resulted in the improved resistance
      of recipients to HSV infection. Normal mice inoculated with T6S cells and exposed
      to HSV had an 80% mortality rate, when given GR-MNC they had a 95% survival rate.
      The suppressor cell activity of T6S cells was clearly counteracted by GR-MNC in
      vitro in a mixed lymphocyte-tumor cell reaction. The type of cells responsible
      for anti-suppressor cells in GR-MNC was shown to be a CD4+ CD28+ TCR alpha/beta +
      Vicia villosa lectin-adherent T cell. These results suggest that GR may reverse
      the increased susceptibility of thermally injured mice to HSV infection through
      the induction of CD4+ contrasuppressor T cells.

PMID- 7721346
TI  - Class II cytoplasmic and transmembrane domains are not required for class II
      mediated B cell spreading.
AB  - B cells cultured on immobilized anti-class II monoclonal antibody (mAb) change
      from round to flattened cells, with lamellipodia and filopodia. This change in
      cell morphology, termed 'spiders', occurs within 30 min upon culture and is
      mediated through either I-A or I-E molecules. Class II molecules that are
      defective in mediating protein kinase C (PKC) due to the deletions of both alpha
      and beta chain's cytoplasmic (Cy) domain sequences can induce spider formation. B
      cell transfectants that express chimeric MHC class II/class I molecules, where
      the ectodomains are class II sequences and the transmembrane and Cy domains are
      class I sequences also form spiders when cultured on anti-class II mAb. The
      spider morphology is not induced by either anti-immunoglobulin (Ig) or anti-MHC
      class I mAb. Treatment of B cells to increase intracellular cAMP, a component of
      the class II signaling pathway also results in spider formation with the same
      kinetics and percent change in the responding population as that induced by anti
      class II mAb. Cytochalasin A treatment which disrupts cytoskeletal actin
      filaments and the tyrosine kinase inhibitor, genistein, both inhibit spider
      formation. Actin redistributes from a concentric ring in round cells to the ends
      of the filopodia in the spiders. The mechanism of spider induction whether
      resultant from second messengers following class II signaling or from non
      signaling-induced physical interactions of class II with intracellular
      cytoskeletal components only requires the extracellular domains of class II. The
      biologic relevance of B-cell spiders is currently not known but has been reported
      to be associated with class II signal transduction and efficient Ag presentation.

PMID- 7721347
TI  - Changes in LAK susceptibility of tumor cells as their MHC class I antigen
      expression levels regenerate after treatment at pH 3.0.
AB  - Changes in LAK susceptibility of tumor cells in which MHC class I antigen
      expression was undergoing regeneration following treatment at pH 3.0, were
      studied. P815 (murine mastocytoma) and RAJI (human B-cell leukemia) cell lines
      were briefly exposed to pH 3.0 buffer which brought down the MHC class I
      expression on these cells by 70-80% and resulted in a 3-fold increase in their
      susceptibility to murine and human LAK cells, respectively. During the MHC class
      I regeneration phase, LAK susceptibility fell and reached normal levels at a time
      point when MHC class I antigens had regenerated to a level which was 60-70% of
      the normal. Highly significant inverse correlations were obtained between LAK
      susceptibility and the log of MHC class I antigen expression, for both P815 and
      RAJI cell lines. These results indicate that during the MHC class I regeneration
      phase, there is an inverse correlation between MHC class I antigen levels and LAK
      susceptibility. Moreover, these results also suggest that the extent of change in
      LAK susceptibility may depend upon the levels of basal MHC class I expression on
      the tumor cells.

PMID- 7721349
TI  - Sequence of the dog immunoglobulin alpha and epsilon constant region genes.
AB  - The immunoglobulin alpha (IGHAC) and epsilon (IGHEC) germline constant region
      genes were isolated from a dog liver genomic DNA library. Sequence analysis
      indicates that the dog IGHEC gene is encoded by four exons spread out over 1.7
      kilobases (kb). The IGHAC sequence encompasses 1.5 kb and includes all three
      constant region coding exons. The complete exon/intron sequence of these genes is
      described.

PMID- 7721348
TI  - Cloning and analysis of gene regulation of a novel LPS-inducible cDNA.
AB  - The expression of many genes is altered upon the activation of macrophages by
      bacterial LPS. These genes play a crucial role in the orchestration of various
      responses to protect the host against infection. A novel 2.3 kilobase (kb) cDNA,
      designated IRG1, was obtained from a cDNA library prepared with RNA isolated from
      RAW 264.7 following lipopolysaccharide stimulation. Sequence analysis of the
      clone revealed no identity to any known genes but showed the presence of many
      potential phosphorylation sites suggesting that IRG1 protein product may be
      regulated at this level. Furthermore, IRG1 contains the motif for
      glycosaminoglycan attachment site, implying that IRG1 may be a proteoglycan. By
      interspecific back-cross analysis, Irg1 was mapped to mouse chromosome 14 linked
      to Tyrp2 and Rap2a. The IRG1 message appears 1.5 h following LPS exposure and its
      induction was not dependent on new protein synthesis. In fact, cycloheximide
      induced the expression of IRG1, suggesting that a protein repressor prevents the
      expression of IRG1 when uninduced. The role of the protein kinase A pathway in
      regulating the induction of IRG1 by LPS is questionable, because although
      forskolin inhibited its induction, neither dibutyrl-cAMP nor 8-(4
      chlorophenylthio)-cAMP had much effect on its expression. In contrast, activation
      of protein kinase C potentiated the LPS response. Chelation of extracellular
      calcium inhibited IRG1 4 h after LPS induction, while increasing intracellular
      calcium had little effect on the levels of the IRG1 transcript. Inhibiting
      tyrosine phosphorylation abrogated the induction of IRG1 by LPS. Hence, the
      induction of IRG1 by LPS is mediated by tyrosine kinase and protein kinase C
      pathway.

PMID- 7721350
TI  - Definition of a novel complementation group in MHC class II deficiency.
AB  - In this study we analyzed fibroblasts derived from an MHC class II deficiency
      patient (type III bare lymphocyte syndrome). Northern blot analysis showed that
      upon induction with IFN-gamma these fibroblasts did not express HLA class II
      genes and displayed a strongly reduced level of HLA class I gene expression when
      compared with fibroblasts of a healthy individual. However, when analyzed by RT
      polymerase chain reaction (PCR), residual expression could be detected for HLA
      DRA, DPB, and DQA, but not for HLA-DRB, DPA, and DQB. The lack of HLA-DRB
      transcripts in the patient fibroblasts and the high degree of sequence
      polymorphism of HLA-DRB were exploited in the further analysis of these
      fibroblasts. Thus far, at least three, and probably four, complementation groups
      have been defined among patient-derived and experimentally-derived MHC class II
      negative cell lines. Transient heterokaryons between the patient fibroblasts and
      representative B-lymphoblastoid cell lines from each of the complementation
      groups were analyzed by RT-PCR and Southern blotting, using HLA-DRB-specific
      primers and biotin-labeled sequence specific oligonucleotides, respectively.
      These analyses showed that the fibroblasts of this particular patient belonged to
      a novel complementation group in MHC class II deficiency.

PMID- 7721351
TI  - Sequence and diversity of rabbit T-cell receptor gamma chain genes.
AB  - The nucleotide sequences of one constant (C), six variable (V), and two joining
      (J) gene segments coding for the rabbit T-cell receptor gamma chain (Tcrg) were
      determined by directly sequencing fragments amplified by the cassette-ligation
      mediated polymerase chain reaction. The Tcrg-C gene segment did not encode a
      cysteine residue for connection to the Tcr delta chain in the connecting region,
      and two variant forms of the Tcrg-C gene segment were generated by alternative
      splicing, like the human Tcrg-C2 gene. Five of six rabbit Tcrg-V gene segments
      belonged to the same family and displayed similarity to five productive human
      Tcrg-V1 family genes as well as the mouse Tcrg-V5 gene. The remaining rabbit Tcrg
      V gene segment displayed similarity to the human Tcrg-V3 gene. Both rabbit Tcrg-J
      gene segments displayed similarity to the human Tcrg-J2.1 and 2.3, respectively.
      These findings suggested that the genomic organization of rabbit Tcrg genes is
      more similar to that of human than of mouse Tcrg genes.

PMID- 7721352
TI  - Separation of multiple genes controlling the T-cell proliferative response to IL
      2 and anti-CD3 using recombinant congenic strains.
AB  - T lymphocytes of the strain BALB/cHeA exhibit a low proliferative response to IL
      2 and a high response to the anti-CD3 monoclonal antibodies, while the strain
      STS/A lymphocyte response to these stimuli is the opposite. We analyzed the
      genetic basis of this strain difference, using a novel genetic tool: the
      recombinant congenic strains (RCS). Twenty BALB/c-c-STS/Dem (CcS/Dem) RCS were
      used, each containing a different random set of approximately 12.5% of the genes
      from STS and the remainder from BALB/c. Consequently, the genes participating in
      the multigenic control of a phenotypic difference between BALB/c and STS become
      separated into different CcS strains where they can be studied individually. The
      strain distribution patterns of the proliferative responses to IL-2 and anti-CD3
      in the CcS strains are different, showing that different genes are involved. The
      large differences between individual CcS strains in response to IL-2 or anti-CD3
      indicate that both reactions are controlled by a limited number of genes with a
      relatively large effect. The high proliferative response to IL-2 is a dominant
      characteristic. It is not caused by a larger major cell subset size, nor by a
      higher level of IL-2R expression. The response to anti-CD3 is known to be
      controlled by polymorphism in Fc gamma receptor 2 (Fcgr2) and the CcS strains
      carrying the low responder Fcgr2 allele indeed responded weakly. However, as
      these strains do respond to immobilized anti-CD3, while the STS strain does not,
      and as some CcS strains with the BALB/c allele of Fcgr2 are also low responders,
      additional gene(s) of the STS strain strongly depress the anti-CD3 response. In a
      backcross between the high responder and the low responder strains CcS-9 and CcS
      11, one of these unknown genes was mapped to the chromosome 10 near D10Mit14. The
      CcS mouse strains which carry the STS alleles of genes controlling the
      proliferative response to IL-2 and anti-CD3 allow the future mapping, cloning,
      and functional analysis of these genes and the study of their biological effects
      in vivo.

PMID- 7721353
TI  - Evolution of the immunoglobulin M constant region genes of salmonid fish, rainbow
      trout (Oncorhynchus mykiss) and Arctic charr (Salvelinus alpinus): implications
      concerning divergence time of species.

PMID- 7721354
TI  - Ten polymorphic DNA loci, including five in the rat MHC (RT1) region, form a
      single linkage group on rat chromosome 20.

PMID- 7721355
TI  - Structure of novel rat major histocompatibility complex class II genes RT1.Ha and
      Hb.

PMID- 7721356
TI  - Isolation of a functional cDNA encoding the RT1.Au MHC class I heavy chain by a
      novel PCR-based method.

PMID- 7721357
TI  - An analysis of the antigen binding site of RT1.Aa suggests an allele-specific
      motif.

PMID- 7721358
TI  - Genomic organization and sequence of the rat major histocompatibility complex
      class Ia gene RT1.Au.

PMID- 7721359
TI  - Sequencing of a new HLA-B41 subtype (B*4102) that occurs with a high frequency in
      the Caucasoid population.

PMID- 7721360
TI  - Three new immunoglobulin kappa variable (Igk-V) gene segments in the mouse.

PMID- 7721361
TI  - Polymorphism of the human factor H-related gene (FHR-1) and of factor H in a west
      African individual.

PMID- 7721362
TI  - Are fluoroquinolones safe in children?

PMID- 7721363
TI  - Classification and treatment of pneumonia.

PMID- 7721364
TI  - Plague--clinical features and management.

PMID- 7721365
TI  - Laboratory diagnosis of plague.

PMID- 7721366
TI  - Control and prevention of human plague.

PMID- 7721367
TI  - Chronic diarrhea in children of tropics.
AB  - Syndrome of prolonged diarrhea is quite frequent in tropical children. Careful
      clinical appraisal can help in separating these children into distinct clinical
      entities which have different underlying etiological factors. In most cases
      diagnosis is possible on clinical grounds supplemented by simple investigations.
      A step by step approach as outlined is extremely helpful in planning a rational
      management.

PMID- 7721368
TI  - Parenteral and enteral nutrition in gastrointestinal disease.

PMID- 7721369
TI  - Diagnostic upper GI endoscopy for hemetemesis in children: experience from a
      pediatric gastroenterology centre in north India.
AB  - Upper GI endoscopies were done in 236 children (upto 12 years of age) presenting
      with history of hemetemesis. Varices were the commonest lesions (in 39.41%)
      followed by esophagitis (23.73%). Gastritis, gastric ulcer, duodenal ulcer and
      oesophageal ulcers were identified in 7.20%, 1.27%, 0.42% and 0.42% cases
      respectively. Cause of bleeding could not be ascertained in 27.54% cases. No
      significant premedication or procedure related complications were observed. Upper
      GI endoscopy is thus a safe and useful mode of investigation in cases of
      hemetemesis in children.

PMID- 7721370
TI  - Chronic inflammatory bowel disease.

PMID- 7721371
TI  - Childhood hepatitis.

PMID- 7721372
TI  - Changing pattern of chronic liver disease (CLD) in India.

PMID- 7721373
TI  - Kerosene oil poisoning in children: a hospital-based prospective study in Sri
      Lanka.
AB  - This is a prospective hospital based study of 526 cases of kerosene oil poisoning
      seen during a 10 year period. There were 5 cases of deliberate self poisoning and
      1 case of attempted homicide. 520 cases were accidental. Pneumonitis occurred in
      299 children of whom 253 had vomited after kerosene oil ingestion. There were 3
      deaths.

PMID- 7721374
TI  - A randomised multicentre study to compare the safety and efficacy of albendazole
      and metronidazole in the treatment of giardiasis in children.
AB  - A randomised control multicentre study to compare the safety and efficacy of
      albendazole and metronidazole in the treatment of giardiasis in children is
      reported. One hundred and fifty children of either sex (age range: 2-10 years)
      were randomised to receive either a single dose of 400 mg of albendazole
      suspension, or 22.5 mg/kg/day of metronidazole in 3 divided doses for 5
      consecutive days. At the end of therapy, majority of children in both treatment
      groups were symptom free. Two days after completion of therapy, 97% of children
      in both treatment groups were giardia free in the stools. Side effects were noted
      in 3 children in the albendazole group, and in 20 children in the metronidazole
      group. We conclude that albendazole suspension is as effective as metronidazole
      in the treatment of giardial infection in children. It is safe and has fewer side
      effects as compared to metronidazole.

PMID- 7721375
TI  - Nutritional status of married adolescent girls in rural Rajasthan.
AB  - Adolescence is period of rapid growth and development. The present study was
      undertaken to assess the nutritional status of 941 adolescent girls, aged 10-18
      years belonging to Scheduled Caste communities in rural Rajasthan, using the
      probability proportionate to size sampling procedure. Data on 93 married
      adolescent girls was analysed in detail. Nutritional status of the subjects was
      assessed by anthropometry, dietary intake and by clinical examination of
      nutritional deficiency disorders. Anthropometric measurements were recorded for
      height, weight, chest circumference, MUAC and TSF using standardised techniques.
      On comparing the present study's data with ICMR's study data (1956-65) it was
      found that there has been a significant improvement in the height, weight and
      chest circumference of the adolescent girls but the values were below the well-to
      do group study data. Dietary intake was assessed by 24 hours recall method. The
      dietary intake was compared against ICMR's RDA. It was found that the diets were
      deficient in calories by 30 to 40% in proteins by 25 to 37%, by 39 to 55% in iron
      and by 10 to 34% in vitamin A. 78% of the subjects suffered from various grades
      of anaemia and 40% of the subjects had B-complex deficiency.

PMID- 7721376
TI  - Breast milk versus infant formulas: effects on intestinal blood flow in neonates.
AB  - The differences between breast milk and infant formulas have been a popular
      subject of many recent studies. Most concern the chemical and biological
      characteristics of breast milk and infant formulas, but little work has been done
      about hemodynamic changes in the splanchnic circulation. In term neonates (n =
      22) we evaluated the effect of breast milk, adapted cow's milk formula, and
      nucleotide supplemented cow's milk formula on intestinal blood flow. To determine
      the blood flow velocity and estimate volume flow, pulsed Doppler ultrasound of
      the superior mesenteric artery (SMA) was performed prefeeding and 15, 45, and 90
      minutes following feeding. When pre- and postprandial blood flow features of
      babies were compared among in their groups according to nutrition post prandial
      blood flow velocity and volume flow were increased significantly over baseline in
      all three groups. While there was no significant difference between the
      postprandial blood flow parameters of the breast milk and adapted cow's milk
      formula-fed groups, the nucleotide supplemented cow's milk formula-fed group had
      significantly higher postprandial blood flow velocity and volume flow.

PMID- 7721377
TI  - Quantitation of T cells in venous blood of healthy neonates.
AB  - Quantitation of T Cells in blood is the part of the diagnostic workup for
      cellular immunity. Specimens of venous blood were collected within 24 hours of
      birth from 51 healthy, appropriate for gestational age infants. T lymphocytes
      were identified on the basis of their ability to form rosettes with sheep
      erythrocytes. The lymphocytes were harvested from peripheral venous blood, which
      is considered to be more representative of the immune status in the newborn than
      the cord blood. In the newborn infants the proportion in T cells was found to be
      considerably diminished in comparison to previously reported values for adults.
      Preterm infants, especially those with gestational age of 34 wk or less had
      significantly lower percentage of T cells in their blood as compared with term
      infants. The proportion of T cells was statistically reduced in infants weighing
      2000 g or less in contrast to those weighing 2500 g or more.

PMID- 7721378
TI  - Choledocholithiasis in childhood.

PMID- 7721379
TI  - Use of plasmid DNA analysis in diagnosis of catheter related enterococcal
      septicemia in a neonate.

PMID- 7721380
TI  - The importance of MRI in diagnosis of Friedreich ataxia.

PMID- 7721381
TI  - Delayed hemolytic transfusion reaction in a thalassemic child.

PMID- 7721382
TI  - Joubert syndrome with polydactyly and optic coloboma in two sibs.

PMID- 7721383
TI  - Congenital glioblastoma.

PMID- 7721384
TI  - Fluorescent-actin staining (FAS) test: a novel assay to detect enteropathogenic
      E. coli.

PMID- 7721385
TI  - Regional heterogeneity of arterial structural changes.
AB  - Arterial structural changes in experimental models of hypertension and restenosis
      differ between vessel types and within vessels. Inspired by the diversity of
      short-term functional responses to vasoactive agents, hypotheses are presented
      with respect to the heterogeneity of structural alterations. Considered are the
      multifactorial nature of smooth muscle cell growth control and the possibility
      that vascular smooth muscle is not homogeneous but composed of different smooth
      muscle cell populations. These hypotheses may help explain the origin of both
      intervascular and intravascular heterogeneity of vascular structural responses.

PMID- 7721386
TI  - Effect of antihypertensive treatment on small arteries of patients with
      previously untreated essential hypertension.
AB  - In a double-blind randomized trial, the effects of treatment with an angiotensin
      converting enzyme (ACE) inhibitor (perindopril) and a beta-blocker (atenolol) on
      small artery structure were compared in previously untreated essential
      hypertensive patients. Subjects (diastolic blood pressure > or = 100 and < or =
      120 mm Hg) were randomly assigned to treatment for 12 months with either
      perindopril (n = 13, 4 to 8 mg/d) or atenolol (n = 12, 50 to 100 mg/d); the
      dosage was adjusted upward and in some cases combined (n = 5, perindopril; n = 2,
      atenolol) with thiazide diuretic to achieve target blood pressure (diastolic
      blood pressure below 90 mm Hg). Before and at the end of treatment, gluteal
      biopsies were taken under local anesthetic; from these biopsies, two small
      arteries were dissected and mounted on a myograph for morphometry. The reduction
      in blood pressure with atenolol (drop in mean blood pressure 28.4 +/- 1.8 mm Hg)
      was greater than with perindopril (20.6 +/- 1.8 mm Hg, P < .05). Perindopril
      treatment caused an increase in small artery diameter (231 +/- 14 to 274 +/- 13
      microns, P < .05) and a reduction in the ratio of media thickness to lumen
      diameter (7.94 +/- 0.65% to 5.96 +/- 0.42%, P < .05), whereas atenolol had no
      effect (246 +/- 14 to 231 +/- 13 microns and 7.14 +/- 0.47% to 6.79 +/- 0.45%,
      respectively). The change in small artery morphology caused by perindopril was
      not accompanied by any change in media cross-sectional area, suggesting that the
      change was due to "remodeling."(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721387
TI  - pHi, [Ca2+]i, and myosin phosphorylation in histamine- and NH4(+)-induced swine
      carotid artery contraction.
AB  - We examined the interaction among changes in pHi, [Ca2+]i, myosin light-chain
      phosphorylation, and contraction in arterial smooth muscle stimulated by
      histamine, NH4+, Tris+, and/or changes in extracellular pH (pHo). We loaded swine
      carotid medial tissues with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein to
      measure pHi or aequorin to measure [Ca2+]i. Incubation of tissues in NH4+
      increased pHi, [Ca2+]i, myosin phosphorylation, and force. Washout of NH4+
      decreased pHi and transiently further increased in [Ca2+]i and force. Incubation
      of tissues in a similar concentration of Tris+ or increasing pHo also increased
      pHi; however, there were only modest changes in [Ca2+]i and force. Increasing
      extracellular pH coincidentally with washout of NH4+ prevented the decrease in
      pHi but did not affect the NH4+ washout-induced contraction. These data suggest
      that NH4+ altered [Ca2+]i and contraction by mechanisms other than its effects on
      pHi. The type of pH buffer did not affect the [Ca2+]i, myosin phosphorylation, or
      stress response to histamine stimulation. The time course of changes in pHi was
      much slower than the time course of histamine-induced changes in [Ca2+]i, myosin
      phosphorylation, and stress. Addition of 10 mmol/L NH4+ concurrently with
      histamine aborted the histamine-induced decrease in pHi and significantly slowed
      the histamine-induced increase in [Ca2+]i, myosin phosphorylation, and stress.
      There was little effect on histamine-induced increases in [Ca2+]i, myosin
      phosphorylation, or contraction when three other protocols aborted the histamine
      induced decrease in pHi. These data show that incubation in NH4+ can alter
      [Ca2+]i and contraction in both unstimulated and histamine-stimulated smooth
      muscle. However, these effects were not caused by NH4(+)-dependent changes in
      pHi.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721388
TI  - Enhanced responses of the basilar artery to activation of endothelin-B receptors
      in stroke-prone spontaneously hypertensive rats.
AB  - We tested the hypothesis that responses of the basilar artery to selective
      activation of endothelin-B receptors are altered during chronic hypertension.
      Using a cranial window in anesthetized rats, we examined responses of the basilar
      artery to a selective endothelin-B receptor agonist, IRL 1620, in stroke-prone
      spontaneously hypertensive rats (SHRSP). Under control conditions, baseline
      basilar artery diameter was smaller in SHRSP (196 +/- 8 microns [mean +/- SEM])
      than in normotensive Wistar-Kyoto rats (WKY) (245 +/- 9 microns, P < .05).
      Topical application of IRL 1620 (10(-8) mol/L) dilated the basilar artery by 27
      +/- 5% in WKY and 56 +/- 4% in SHRSP (P < .05). Dilatation of the basilar artery
      in response to sodium nitroprusside was similar in WKY and SHRSP. In contrast,
      acetylcholine-induced vasodilatation in SHRSP was markedly impaired. NG-Nitro-L
      arginine methyl ester and NG-nitro-L-arginine, inhibitors of nitric oxide
      synthase, inhibited IRL 1620-induced vasodilatation in WKY. Neither NG-nitro-L
      arginine methyl ester nor indomethacin attenuated vasodilatation produced by IRL
      1620 in SHRSP. The major finding is that dilator responses of the basilar artery
      to selective activation of endothelin-B receptors are paradoxically enhanced in
      SHRSP compared with WKY. Dilator responses of the basilar artery to endothelin-B
      receptor activation are mediated by endothelium-derived relaxing factor in WKY.
      In contrast, responses to activation of endothelin receptors in SHRSP do not
      depend on the production of nitric oxide or prostanoids.

PMID- 7721389
TI  - Effect of chronic treatment of adult spontaneously hypertensive rats with an
      endothelin receptor antagonist.
AB  - We previously showed that endothelin-1 expression was increased in vascular
      endothelium of deoxycorticosterone acetate-salt hypertensive rats, whereas in
      spontaneously hypertensive rats (SHR) it is similar to or less than that in
      normotensive rats. Treatment with the combined endothelin type A/endothelin type
      B receptor antagonist bosentan moderately reduced blood pressure rise and nearly
      completely blunted the development of vascular hypertrophy, particularly in small
      arteries, in the deoxycorticosterone acetate-salt hypertensive model, suggesting
      a paracrine role for vascular endothelin-1 in the induction of blood vessel
      hypertrophy in some forms of experimental hypertension. In the present study we
      examined the effect of chronic oral treatment for 4 weeks of 12-week-old SHR and
      Wistar-Kyoto rats (WKY) with 100 mg/kg per day bosentan. Blood pressure rose to
      hypertensive levels similarly in bosentan-treated and untreated SHR; systolic
      pressure of WKY was also unaffected. The wet weights of the heart, of aortic
      segments, and of the mesenteric arterial bed were similar in treated and
      untreated SHR. When coronary, renal arcuate, mesenteric, and femoral small
      arteries were evaluated on a wire myograph, the media width and media-to-lumen
      ratio were greater and the lumen diameter was smaller in vessels from SHR
      relative to those from WKY, except in small arteries from the renal cortex, in
      which the lumen was not significantly different in both strains. The media cross
      sectional area of small arteries fom the four vascular beds was similar in both
      strains. Identical morphometric parameters were found in the four vascular beds
      in bosentan-treated and untreated rats of eh strain.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7721390
TI  - ETA and ETB receptors mediate contraction to endothelin-1 in renal artery of
      aging SHR. Effects of FR139317 and bosentan.
AB  - We characterized vascular endothelin receptors of the renal artery from adult (12
      to 16 weeks of age) and old (72 to 76 weeks) spontaneously hypertensive rats
      (SHR) and age-matched Wistar-Kyoto rats (WKY). Vessels were suspended in organ
      chambers (37 degrees C, aerated with 95% O2/5% CO2), and isometric tension was
      recorded. The endothelin-A (ETA) receptor antagonist FR139317, the combined
      ETA/ETB receptor antagonist bosentan, and the ETB-selective agonist sarafotoxin
      S6c were used. In old (and less so in adult) SHR, cumulative concentration
      contraction curves to endothelin-1 showed a small contraction resistant to
      FR139317 (10(-5) mol/L) at 3 x 10(-9) to 10(-8) mol/L endothelin-1, which was
      completely inhibited by bosentan (10(-5) mol/L). This FR139317-resistant
      contraction to endothelin-1 was not present in WKY. Furthermore, in the presence
      of FR139317 (10(-5) mol/L), sarafotoxin S6c induced a stronger contraction in old
      SHR than in WKY (P < .05). In rings contracted with norepinephrine, sarafotoxin
      S6c caused endothelium-dependent relaxations in both strains; these relaxations
      were blocked by N omega-nitro-L-arginine methyl ester, indicating that nitric
      oxide is the mediator. In WKY but not SHR, release of nitric oxide by sarafotoxin
      S6c increased with age (P < .05). Thus, both ETA and ETB receptors mediate
      contraction to endothelin-1 in the renal artery from SHR but not WKY. ETB
      receptors on vascular smooth muscle seem to be unmasked with age in SHR, whereas
      those on endothelium (mediating nitric oxide release) exhibit more efficient
      responses with age in WKY.

PMID- 7721391
TI  - Endothelin-1 in rat periaqueductal gray area induces hypertension via
      glutamatergic receptors.
AB  - We investigated the possible relationship between endothelin-1 injection into the
      dorsolateral periaqueductal gray area and the glutamatergic system in the control
      of cardiovascular function. Endothelin-1 was injected into the dorsolateral
      periaqueductal gray area of freely moving rats at doses ranging from 0.1 to 10
      pmol. Endothelin-1 increased arterial blood pressure (from 7.0 +/- 1.6 to 55.0 +/
      4.1 mm Hg, mean +/- SEM) in a dose-dependent manner and induced characteristic
      behavioral changes such as longitudinal rolling of the body (barrel-rolling). DL
      2-Amino-5-phosphonovaleric acid and (5R,10S)-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[D-alpha] cyclohepten-5,10-imine hydrogen maleate, both selective N-methyl
      D-aspartate excitatory amino acid receptor antagonists, but not 6-cyano-7
      nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate excitatory amino acid
      receptor antagonist, significantly decreased endothelin-1-induced cardiovascular
      and behavioral changes (P < .01). Prazosin and propranolol, adrenergic blocking
      agents, and reserpine, a depletor of catecholamine stores, also prevented these
      effects. We propose that the glutamatergic system may exert, via N-methyl-D
      aspartate receptors, a significant influence on endothelin-1-induced
      cardiovascular and behavioral effects after its injection into the periaqueductal
      area.

PMID- 7721392
TI  - Gender difference in endothelial dysfunction in the aorta of spontaneously
      hypertensive rats.
AB  - We investigated endothelium-dependent responses of thoracic aorta isolated from
      age-matched male and female spontaneously hypertensive rats (SHR) to explore
      gender differences in endothelial dysfunction that may contribute to the sexual
      dimorphism observed in the development of hypertension in this strain.
      Endothelium-dependent relaxation in response to acetylcholine (10(-9) to 10(-4)
      mol/L) was significantly greater in female rats than in male rats, although
      impaired responses were seen in both sexes compared with normotensive controls.
      Inhibition of cyclooxygenase by indomethacin (10(-5) mol/L) improved endothelium
      dependent relaxation, but it did not abolish the gender difference. Relaxations
      in response to sodium nitroprusside were identical in denuded aortic rings from
      male and female SHR. Acetylcholine at higher concentrations (10(-6) to 10(-4)
      mol/L) induced endothelium-dependent contraction in intact, quiescent aortic
      rings from male SHR but not in those from female SHR. After incubation with NG
      nitro-L-arginine (10(-4) mol/L), contraction in response to acetylcholine became
      apparent in rings from female SHR, but it was still significantly less pronounced
      than in similarly treated rings from male SHR. Endothelium-dependent contraction
      was prevented by indomethacin in both sexes, suggesting that a cyclooxygenase
      product such as endoperoxide may be mediating this effect. Because responses
      evoked by the thromboxane/endoperoxide receptor agonist U46619 (10(-10) to 10(-6)
      mol/L) were not greater in rings from male SHR than those from female SHR,
      increased smooth muscle responsiveness or higher thromboxane/endoperoxide
      receptor density in the males could not account for the differences in
      endothelium-dependent contraction. These results suggest that sex steroid
      hormones may control endothelium-dependent vascular reactivity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7721393
TI  - Brain kallikrein-kinin system abnormalities in spontaneously hypertensive rats.
AB  - The objective of the present study was to determine whether the brain kallikrein
      kinin system differs between spontaneously hypertensive rats (SHR) and
      normotensive Wistar-Kyoto rats (WKY) and if so, whether any detected differences
      occur before the development of hypertension in SHR. We measured cerebrospinal
      fluid levels of various components of the system in adult and young
      prehypertensive SHR and WKY. Cerebrospinal fluid kinin concentration and
      appearance rate were higher in SHR. Cerebrospinal fluid active kallikrein level
      and kininogenase activity were also higher in adult SHR. In addition,
      cerebrospinal fluid kinin concentration and appearance rate were higher in
      prehypertensive, 5- to 6-week-old SHR compared with age-matched WKY. However, no
      differences in cerebrospinal fluid kallikrein or kininogenase activity were
      observed between the two strains of young rats. Cerebrospinal fluid kinin
      concentration was higher in young versus adult rats of the same strain. In WKY,
      cerebrospinal fluid kallikrein also decreased with age although cerebrospinal
      fluid kallikrein concentration did not decrease in young and adult SHR. Together,
      these data suggest that there is a hyperactive kallikrein-kinin system in the
      brain of SHR that may contribute to the hypertensive state in this animal model.

PMID- 7721394
TI  - Analysis of renal sympathetic nerve responses to stress.
AB  - We studied sympathetic nerve activity responses to acute environmental stress
      (air jet stress) in conscious Wistar-Kyoto, spontaneously hypertensive, and
      borderline hypertensive rats. The borderline hypertensive rats were fed either 1%
      (normotensive) or 8% (hypertensive) NaCl. Renal sympathetic nerve activity
      responses were analyzed with three methods: mean integrated voltage over time,
      power spectrum analysis, and sympathetic peak detection analysis. Measurements of
      mean integrated voltage over time showed that air jet stress increased renal
      sympathetic nerve activity in spontaneously hypertensive rats and in borderline
      hypertensive rats on 8% NaCl but not in the other groups. In the NaCl responders,
      power spectrum analysis of renal sympathetic nerve activity indicated that the
      increase in relative power was at the heart rate frequency, indicating that it
      was related to renal sympathetic nerve discharge coupled to the cardiac cycle.
      Sympathetic peak detection analysis of renal sympathetic nerve activity indicate
      that there was an increase in frequency of sympathetic peaks of greater height
      and shorter duration because of sinoaortic baroreceptor deactivation (increased
      peak frequency) and the recruitment of more active fibers (greater peak height)
      firing with greater synchronization (shorter peak duration). Additional methods
      of analysis of renal sympathetic nerve activity provide information in addition
      to that derived from measurement of mean integrated voltage over time.

PMID- 7721395
TI  - Blood pressure and heat shock protein expression in response to acute and chronic
      stress.
AB  - We previously demonstrated that restraint and pharmacological agents that
      activate sympathetic nervous system activity induce expression of the 70-kD heat
      shock protein (HSP70) in major blood vessels. The magnitude and rapidity in which
      HSP70 is induced in the aorta suggest that it may play a salient role in the
      mechanical properties of vascular smooth muscle. Other investigators have
      reported that HSP70 inducibility is increased in genetically hypertensive
      animals. In this report, we have investigated the effects of acute and chronic (8
      week) exposure to restraint and restraint in the presence of a randomized
      intermittent air jet on the development of hypertension and the induction of
      HSP70 in the aorta and adrenal glands of normotensive adult male Sprague-Dawley
      rats. Acute restraint or air jet resulted in a fivefold to sixfold increase in
      aortic HSP70 mRNA expression. Chronic exposure to restraint reduced the HSP70
      response to acute restraint. In contrast, no adaptation of the HSP70 response to
      acute air jet was observed in aortas of chronically air jet-treated rats. In
      adrenal glands, HSP70 expression was reduced after chronic restraint and air jet,
      indicating that in this tissue, adaptation occurs to both stressors. There was no
      difference in HSP70 expression in unstressed rats that had been chronically
      exposed to restraint or air jet in either adrenal gland or aorta. A significant
      increase (P < .05) in systolic blood pressure developed in air jet-treated
      animals (120 +/- 3 mm Hg) but not in restrained rats (107 +/- 2 mm Hg) compared
      with unstressed controls (106 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721396
TI  - Impaired maze learning and cerebral glucose utilization in aged hypertensive
      rats.
AB  - To elucidate the effects of prolonged hypertension on brain function during
      aging, we examined learning of an eight-arm radial maze task and local cerebral
      glucose utilization in young-adult (3 to 4 months old) and aged (16 to 17 months
      old) spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Young
      adult SHR learned the task more slowly than young-adult WKY, but cerebral glucose
      utilization, measured by the [14C]2-deoxyglucose method in 24 brain structures,
      was not significantly different in the two groups. The aged SHR and WKY exhibited
      impaired learning ability. Cerebral glucose utilization was reduced (13% to 23%)
      in six regions in aged WKY and in 12 regions in aged SHR compared with values in
      the respective young-adult groups. Furthermore, the aged SHR showed a greater
      disturbance of learning acquisition and more profound reduction of cerebral
      glucose utilization in five regions than the aged WKY. In SHR, hypometabolism,
      indicated by a decrease in glucose utilization in 15 brain structures including
      the cerebral cortex, hippocampus, and visual system, was significantly correlated
      with impaired learning acquisition, indicated by an increase in total error
      choices. These findings show that (1) hypertension per se does not impair maze
      learning or cerebral glucose utilization in young-adult rats, and (2) brain
      function is impaired during aging and prolonged hypertension is an additional
      factor facilitating brain dysfunction associated with neuronal hypoactivities,
      resulting in behavioral deterioration including learning disability. Thus, early
      control of hypertension seems important for preventing or reducing brain
      dysfunction in senescence.

PMID- 7721397
TI  - Job status and high-effort coping influence work blood pressure in women and
      blacks.
AB  - Work-related stress has been associated with an increased risk of hypertension
      and more severe cardiovascular problems in white men but has been less studied in
      women and black men. To determine whether the trait of high-effort coping (John
      Henryism) was related to higher blood pressure during work and laboratory
      challenges, we studied a biracial sample of 72 men and 71 women working full time
      outside the home who underwent ambulatory blood pressure monitoring for one 8
      hour workday. This was followed by laboratory monitoring of blood pressure during
      resting baseline and five brief stressors. Women who were high-effort copers and
      had high status jobs had higher diastolic pressures at work and in the lab than
      other women; their pressure levels did not differ from those of men, but other
      women had lower pressures than men. In blacks, the same combination of high
      effort coping plus high job status was similarly associated with high work and
      laboratory diastolic pressure, as well as higher work systolic pressure. The
      trait of high-effort coping was observed in the large majority (71%) of the women
      and blacks who had achieved high status jobs but was seen in a minority (36%) of
      white men with high status jobs and was unrelated to increased blood pressure in
      the latter group.

PMID- 7721398
TI  - Sympathetic activation in obese normotensive subjects.
AB  - Human obesity is characterized by profound alterations in the hemodynamic and
      metabolic states. Whether these alterations involve sympathetic drive is
      controversial. In 10 young obese subjects (body mass index, 40.5 +/- 1.2 kg/m2,
      mean +/- SEM) with normal blood pressure and 8 age-matched lean normotensive
      control subjects, we measured beat-to-beat arterial blood pressure (Finapres
      technique), heart rate (electrocardiogram), postganglionic muscle sympathetic
      nerve activity (microneurography at the peroneal nerve), and venous plasma
      norepinephrine (high-performance liquid chromatography). The measurements were
      performed in baseline conditions and, with the exception of plasma
      norepinephrine, during baroreceptor stimulation and deactivation caused by
      increases and reductions of blood pressure via intravenous infusions of
      phenylephrine and nitroprusside. Baseline blood pressure and heart rate were
      similar in obese and control subjects. Plasma norepinephrine was also similar in
      the two groups. Muscle sympathetic nerve activity, however, was 38.6 +/- 5.1
      bursts per minute in obese subjects and less than half that level in control
      subjects (18.7 +/- 1.3 bursts per minute), the difference being highly
      statistically significant (P < .02). Muscle sympathetic nerve activity and heart
      rate were reduced during phenylephrine infusion and increased during
      nitroprusside infusion, but the changes were about half as great in obese
      subjects as in control subjects. Thus, even in the absence of any blood pressure
      alteration, human obesity is characterized by a marked sympathetic activation,
      possibly because of an impairment of reflex sympathetic restraint. This may be
      involved in the high rate of hypertension and cardiovascular complications seen
      in obesity.

PMID- 7721399
TI  - Modeling hemodynamic profiles by telemetry in the rat. A study with A1 and A2a
      adenosine agonists.
AB  - The newly developed radiotelemetry system offers a number of advantages for the
      measurement of blood pressure and heart rate in laboratory animals. However, no
      available statistical methods permit valid use of the many data gathered with
      this continuous recording of hemodynamic parameters. This study describes
      elaboration and testing of mathematical functions as applied to the measurement
      of the effects of drugs on blood pressure and heart rate in spontaneously
      hypertensive rats. We used parametric functions analogous to those for
      pharmacokinetic studies. Curve fitting is in fact the only approach that provides
      reasonable estimates of hemodynamic kinetic constants. Nonlinear functions were
      assessed by analyzing telemetric hemodynamic effects induced by three adenosine
      receptor agonists with different selectivity for the A1 or A2a receptor. After
      acute administration in conscious rats, the A1 agonist 2-chloro-N6
      cyclopentyladenosine induced dose-related hypotension (eg, 0.03 mg/kg; peak, -70
      mm Hg; time to peak, 0.34 hour) and bradycardia (eg, 0.03 mg/kg; peak, -186 beats
      per minute [bpm]; time to peak, 0.38 hour). The A2a agonist 2-hexynyl-5'-N
      ethylcarboxamidoadenosine induced dose-related hypotension (eg, 0.003 mg/kg;
      peak, -36 mm Hg; time to peak, 0.32 hour) with reflex tachycardia (eg, 0.003
      mg/kg; peak, 152 bpm; time to peak, 0.35 hour). The nonselective adenosine
      agonist 5'-N-ethylcarboxamidoadenosine (0.1 mg/kg) induced hypotension (peak, -75
      mm Hg; time to peak, 2.2 hours) and bradycardia followed by tachycardia (first
      peak, -131 bpm; time to peak, 1.26 hours; second peak, 123 bpm; time to peak,
      13.9 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721400
TI  - Differential gene expression of renin and angiotensinogen in the TGR(mREN-2)27
      transgenic rat.
AB  - Transgenic rats carrying the murine Ren-2 gene represent a monogenetic model of
      hypertension characterized by low plasma renin and high extrarenal expression of
      the transgene. The hypothesis has been raised that stimulated local
      reninangiotensin systems may be responsible for the development of hypertension
      in this model. This study analyzes the effects of the converting enzyme inhibitor
      lisinopril, which specifically interferes with the renin-angiotensin system, and
      the direct vasodilator dihydralazine on the renal and extrarenal expression of
      renin and angiotensinogen. A comparison of gene expression between heterozygous
      and homozygous transgenic and normal Sprague-Dawley rats was also performed. We
      demonstrate high sensitivity of blood pressure toward converting enzyme
      inhibition in transgenic TGR(mREN-2)27 rats. In the kidney, expression of the
      transgene and the endogenous renin gene increased, suggesting that both are
      modulated by lisinopril in a similar manner. On the other hand, blood pressure
      reduction by dihydralazine did not abolish renal renin suppression in transgenic
      rats, indicating that mechanisms different from direct effects of blood pressure
      account for renin suppression. Homozygosity for the transgene led to increased
      Ren-2 expression and higher blood pressure and had opposite effects on
      angiotensinogen expression compared with heterozygous rats. Cardiac hypertrophy
      was reduced by lisinopril but not dihydralazine and was positively correlated
      with cardiac angiotensinogen expression. Increased angiotensin II in the adrenal
      gland of TGR(mREN-2)27 rats, which overexpresses the transgene, provides evidence
      that this leads to enhanced generation of tissue angiotensin II. We conclude that
      expression of the mouse transgene, the endogenous rat renin gene, and the
      angiotensinogen gene is subject to differential tissue-specific regulation.
      Reversal of cardiovascular damage with the converting enzyme inhibitor but not
      dihydralazine suggests that angiotensin II generated locally may be involved in
      the pathogenesis of hypertension and structural changes in TGR(mREN-2)27 rats.

PMID- 7721401
TI  - Renal nerves, renin, and angiotensinogen gene expression in spontaneously
      hypertensive rats.
AB  - We compared the effect of the renal nerves on renal function, plasma renin
      activity, and renal renin and angiotensinogen mRNA contents in Wistar rats and
      spontaneously hypertensive rats (SHR). Rats were anesthetized with sodium
      pentobarbital, the left kidney was exposed, its nerves were sectioned, the ureter
      was cannulated, and a flow probe was placed on the renal artery. The renal nerves
      were stimulated for 1 hour to reduce renal blood flow by 15% and 30%, after which
      blood was removed for measurement of plasma renin activity, and kidneys were
      analyzed for renal renin and angiotensinogen mRNA. Frequency-related reductions
      in filtration rate were similar, from 15% to 50%, as was sodium excretion, from
      30% to 70%, in both SHR and Wistar rats. Basal plasma renin activity and
      responses to nerve stimulation in SHR were approximately half those of Wistar
      rats (all P < .001). SHR renal renin mRNA concentrations were approximately three
      quarters those of Wistar rats and were unchanged by either low- or high-level
      renal nerve stimulation, whereas the higher rate increased renin mRNA
      approximately threefold (P < .05) in the Wistar rats. SHR renal angiotensinogen
      mRNA was one quarter that of the Wistar rats and was unaffected by nerve
      stimulation, whereas in the Wistar rats it was increased threefold (P < .05) by
      the low but not high level of nerve stimulation. These findings show that whereas
      the renal nerves are able to modulate hemodynamic and tubular functions
      relatively normally in SHR, their ability to increase renin release, renal renin,
      and angiotensinogen mRNA levels is depressed.

PMID- 7721402
TI  - Early predictors of 15-year end-stage renal disease in hypertensive patients.
AB  - There has been a continuing increase in the incidence of end-stage renal disease
      (ESRD) in the United States, including the fraction that has been attributed to
      hypertension. This study was done to seek relationships between ESRD and
      pretreatment clinical data and between ESRD and early treated blood pressure data
      in a population of hypertensive veterans. We identified a total of 5730 black and
      6182 nonblack male veterans as hypertensive from 1974 through 1976 in 32 Veterans
      Administration Hypertension Screening and Treatment Program clinics. Their mean
      age was 52.5 +/- 10.2 years, and their mean pretreatment blood pressure was 154.3
      +/- 19.0/100.8 +/- 9.8 mm Hg. During a minimum of 13.9 years of follow-up, 5337
      (44.8%) of these patients died and 245 developed ESRD. For 1055 of these
      subjects, pretreatment systolic blood pressure (SBP) was greater than 180 mm Hg;
      901 were diabetic; 1471 had a history of urinary tract problems; and 2358 of the
      9644 who were treated had an early fall in SBP of more than 20 mm Hg. We used
      proportional hazards modeling to fit multivariate survival models to determine
      the effect of the available pretreatment data and early treated blood pressure
      levels on ESRD. This model demonstrated the independent increased risk of ESRD
      associated with being black or diabetic (risk ratio, 2.2 or 1.8), having a
      history of urinary tract problems (risk ratio, 2.2), or having high pretreatment
      SBP (for SBP 165 to 180 mm Hg, risk ratio was 2.8; for SBP > 180 mm Hg, risk
      ratio was 7.6).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721403
TI  - Angiotensin II and sympathetic activity in sodium-restricted essential
      hypertension.
AB  - Angiotensin II (Ang II) potentiates sympathetic neurotransmission by presynaptic
      facilitation of norepinephrine release. We investigated whether endogenous Ang II
      modulates peripheral sympathetic activity in sodium-depleted essential
      hypertensive patients. We evaluated the effect of intrabrachial infusion of
      saralasin, an Ang II antagonist (5 micrograms/100 mL forearm tissue per minute),
      and benazeprilat, an angiotensin-converting enzyme inhibitor (2 micrograms/100 mL
      forearm tissue per minute), on forearm vasoconstriction (measured by strain-gauge
      venous plethysmography) induced by the application of lower body negative
      pressure (-10 mm Hg for 5 minutes). Both saralasin and benazeprilat (n = 6 for
      each group) blunted the vasoconstrictor action of lower body negative pressure,
      suggesting that circulating Ang II modulates peripheral sympathetic activity. In
      addition, since beta-adrenoceptor stimulation can activate the production of
      vascular Ang II, the effect of saralasin and benazeprilat on lower body negative
      pressure application was evaluated in the presence of isoproterenol (0.09
      microgram/100 mL forearm tissue per minute) and propranolol (10 micrograms/100 mL
      forearm tissue per minute). In two other groups of hypertensive patients,
      isoproterenol infusion increased the release of Ang II in the forearm vasculature
      (arteriovenous values measured by radioimmunoassay). Furthermore, isoproterenol
      potentiated lower body negative pressure-induced vasoconstriction. This
      facilitating effect was abolished by either saralasin or benazeprilat (n = 6 for
      each group). In contrast, in two further groups of patients (n = 6 for each
      group), in the presence of the beta-blocker propranolol saralasin and
      benazeprilat did not alter the vasoconstrictor action of the endogenous
      sympathetic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721404
TI  - Short-term and sustained renal effects of angiotensin II receptor blockade in
      healthy subjects.
AB  - We investigated the short-term and sustained hormonal and renal effects of
      angiotensin II (Ang II) receptor blockade in normotensive healthy volunteers.
      Twenty-four subjects maintained on a fixed sodium diet were randomized to receive
      for 8 days a placebo or 10 or 50 mg doses of the Ang II antagonist irbesartan (SR
      47436, BMS 186295) according to a double-blind, parallel group design. Plasma
      renin activity, plasma immunoreactive Ang II and aldosterone levels, blood
      pressure, renal hemodynamics, and urinary electrolyte excretion were measured for
      8 hours after the first and eighth administration of each dose of irbesartan or
      placebo. Ang II receptor blockade with irbesartan induced a dose-dependent
      compensatory increase in plasma renin activity and plasma angiotensin levels and
      a significant decrease in plasma aldosterone levels. The compensatory rise in
      plasma renin activity and Ang II levels was more pronounced on day 8, reflecting
      a long duration of the blocking effect of irbesartan. Irbesartan induced small
      changes in blood pressure and did not significantly modify renal blood flow and
      glomerular filtration rate. However, a significant decrease in filtration
      fraction was observed during receptor blockade on days 1 and 8. The tubular
      effects of irbesartan were characterized by a dose-dependent increase in sodium
      and chloride excretions. Interestingly, the cumulative natriuretic response to
      Ang II receptor blockade was similar on days 1 and 8, suggesting that in these
      subjects, renal Ang II receptors are not blocked over 24 hours during repeated
      administration even though this antagonist has a long duration of action (t1/2 of
      15 to 17 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721405
TI  - Cardiovascular development after enalapril in spontaneously hypertensive and
      Wistar-Kyoto rats.
AB  - We studied the long-term effects after withdrawal of enalapril, an angiotensin
      converting enzyme inhibitor, on tail systolic pressure and cardiovascular
      structural properties in spontaneously hypertensive rats (SHR) and Wistar-Kyoto
      rats (WKY). Observations in control rats were from 4 to 35 weeks of age, whereas
      treated rats received enalapril from 4 to 20 weeks and were studied for a further
      15 weeks. We measured blood pressure and the ratio of left ventricle weight to
      body weight and derived methoxamine log dose-perfusion pressure curves in the
      isolated hindquarter bed. From the changes in resistance properties we also
      estimated the changes in structure using a model developed previously. During
      therapy, blood pressure was depressed to a common value in both strains. After
      drug withdrawal, by age 35 weeks, previously treated SHR developed only mild
      hypertension, whereas blood pressure of WKY had recovered to the corresponding
      control level. At 21 weeks, soon after enalapril was stopped, left ventricular
      development was depressed in both strains; the depression was slightly greater in
      SHR, but that of vascular resistance was proportionately similar in each strain.
      Late cardiovascular development between 21 and 35 weeks was attenuated in the
      previously treated groups. For the left ventricle, it was similar in each strain,
      but for the vasculature, late development was relatively smaller in SHR than WKY.
      In the former, the pattern of development between 21 and 35 weeks was the same as
      in untreated controls and appeared to be mediated in response to the rise in
      blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721406
TI  - Effectiveness of enalapril versus nifedipine to antagonize blood pressure and the
      renal response to endothelin in humans.
AB  - Endothelin-1 infusion into humans to obtain pathophysiological plasma levels
      causes mild hypertension, strong renal vasoconstriction, and sodium retention. We
      studied whether oral use of the angiotensin-converting enzyme inhibitor enalapril
      (20 mg BID) or the calcium channel blocker nifedipine (60 mg OD) could attenuate
      these effects of endothelin-1 (2.5 ng/kg per minute for 90 minutes) in six
      healthy volunteers. Endothelin infusion alone increased plasma endothelin from
      3.0 +/- 0.3 to 8.8 +/- 1.0 pmol/L (P < .05). Blood pressure rose by approximately
      6 mm Hg (P < .05). Renal function changes were relatively large: Renal blood flow
      decreased from 941 +/- 76 to 729 +/- 118 mL/min (P < .05) and glomerular
      filtration rate from 105 +/- 9 to 92 +/- 10 mL/min (P < .05); renal vascular
      resistance increased from 101 +/- 7 to 152 +/- 20 mm Hg.min/L (P < .05); and
      sodium excretion decreased from 158 +/- 54 to 86 +/- 27 mumol/min (P < .05).
      Enalapril treatment reduced blood pressure from 94 +/- 2 to 87 +/- 3 mm Hg (P <
      .05) and prevented the hypertensive response to endothelin. By contrast, despite
      renal predilatation, endothelin reduced renal blood flow strongly (from 1063 +/-
      127 to 763 +/- 100 mL/min, P < .05), although maximal renal vascular resistance
      was numerically lower (124 +/- 11 mm Hg.min/L) than during endothelin alone (P <
      .05). Glomerular filtration rate fell from 118 +/- 11 to 108 +/- 11 mL/min (P <
      .05). Enalapril did not alter the antinatriuretic effect of endothelin.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7721407
TI  - 11 beta-Hydroxysteroid dehydrogenase and its inhibitors in hypertensive
      pregnancy.
AB  - Preeclampsia is accompanied by amplification of the sodium retention that is a
      feature of normal pregnancy. Recent evidence suggests that mineralocorticoid
      receptor activation is increased in preeclampsia, but classic mineralocorticoids
      (aldosterone, 11-deoxycorticosterone) are not present in excess. Cortisol can act
      as a mineralocorticoid receptor agonist only when its renal inactivation to
      cortisone by 11 beta-hydroxy-steroid dehydrogenase is impaired, for example, in
      congenital enzyme deficiency and after administration of exogenous inhibitors
      (eg, licorice). Endogenous inhibitors of this enzyme have been detected in human
      urine and are increased in pregnancy. To establish whether cortisol causes
      mineralocorticoid excess in hypertensive pregnancy and whether endogenous
      inhibitors of 11 beta-hydroxysteroid dehydrogenase are responsible, we studied 25
      hypertensive pregnant patients (13 with preeclampsia and 12 with gestational
      hypertension), 16 normotensive pregnant subjects, and 13 nonpregnant control
      subjects. Concentrations of plasma renin and aldosterone were increased in
      pregnancy, but less so in hypertensive pregnancy. Plasma potassium and urinary
      electrolytes were not different between the groups. Plasma cortisol was increased
      in pregnancy but not different in hypertensive pregnancy, and urinary cortisol,
      plasma and urinary cortisone, and urinary tetrahydrocortisol and
      tetrahydrocortisone were not different between the groups. Endogenous inhibitors
      of 11 beta-hydroxysteroid dehydrogenase were more active in urine from pregnant
      women but were not increased further in hypertensive pregnancy. There were no
      differences in these parameters between patients with preeclampsia and
      gestational hypertension. We conclude that deficient inactivation of cortisol to
      cortisone does not contribute to the sodium retention of normotensive or
      hypertensive pregnancy and that endogenous inhibitors of 11 beta-hydroxysteroid
      dehydrogenase have no evident pathophysiological significance in pregnancy.

PMID- 7721408
TI  - Atrial natriuretic peptide and hemodynamic changes during normal human pregnancy.
AB  - We compared plasma atrial natriuretic peptide (ANP) and cGMP levels during normal
      pregnancy--a condition characterized by hypervolemia, high cardiac output, and
      decreased vascular resistance--with postpartum levels and assessed their relation
      to pregnancy-induced hemodynamic changes. Humoral and hemodynamic variables were
      measured in healthy women subjects in the supine and upright postures at each
      trimester of pregnancy and postpartum. Supine plasma ANP was increased throughout
      pregnancy (32 +/- 5, 21 +/- 3, and 19 +/- 2 versus 15 +/- 1 pmol.L-1,
      respectively, at each trimester versus postpartum), as was cGMP (8.6 +/- 1, 7.1
      +/- 1, and 6.6 +/- 1 versus 5.6 +/- 1 nmol.L-1), and their increments were
      directly related (r = .68, P < .01). Both ANP and cGMP levels did not differ from
      postpartum levels after subjects stood. Supine stroke volume was initially
      increased but declined below postpartum levels in late pregnancy (69 +/- 4, 60 +/
      3, and 44 +/- 3 versus 58 +/- 4 mL.m-2), whereas after subjects stood it was
      always higher (56 +/- 3, 58 +/- 3, and 49 +/- 2 versus 44 +/- 2 mL.m-2); thus,
      stroke volume tended to increase in response to standing in late pregnancy.
      Supine cardiac index had a similar trend, which was opposite to that of total
      peripheral resistance (1213 +/- 62, 1265 +/- 79, and 1729 +/- 89 versus 1654 +/-
      92 dyne.s-1.cm-5.m-2).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721409
TI  - Natriuretic response to neutral endopeptidase inhibition is blunted by enalapril
      in healthy men.
AB  - We studied six healthy male subjects in a randomized, placebo-controlled, single
      blind fashion to determine the comparative effects on renal hemodynamics and
      natriuresis of the angiotensin-converting enzyme inhibitor enalapril (5 mg on
      each of 5 days preceding the study), the neutral endopeptidase inhibitor
      candoxatrilat (200 mg IV), and the combination of enalapril and candoxatrilat.
      Enalapril pretreatment alone, compared with placebo, produced slight
      nonsignificant increments in absolute and fractional sodium excretions and a
      marked increase in effective renal plasma flow but no change in glomerular
      filtration rate. Candoxatrilat alone produced marked augmentation of both
      absolute and fractional sodium excretions. The candoxatrilat-mediated increment
      in absolute sodium excretion was significantly correlated with increases in
      urinary cGMP and plasma atrial natriuretic peptide in response to this drug, but
      neither effective renal plasma flow nor glomerular filtration rate was altered
      compared with placebo. Combining enalapril pretreatment with candoxatrilat
      significantly attenuated the increments in absolute and fractional sodium
      excretions in response to the neutral endopeptidase inhibitor. Blood pressure was
      reduced by enalapril alone compared with placebo, whereas candoxatrilat treatment
      alone led to a marginal but significant enhancement of blood pressure. The
      combination of enalapril and candoxatrilat abolished any significant blood
      pressure change compared with placebo. Thus, candoxatrilat-mediated natriuresis
      occurs via a renal tubular rather than glomerular mechanism and is blunted by
      enalapril. This attenuation by enalapril may occur by interference with
      angiotensin II-dependent effects on the renal tubule or on systemic blood
      pressure.

PMID- 7721410
TI  - Spectral analysis of blood pressure variability in heart transplant patients.
AB  - The cardiac transplant patient provides a unique model for the study of blood
      pressure variability in the absence of heart rate variability. We examined the
      harmonic and fractal components of blood pressure variability in 14 heart
      transplant patients (12 men, 2 women; 21 to 62 years of age) and in age-and sex
      matched control subjects during seated rest, supine rest, and supine rest with
      fixed-pace breathing (12 respirations per minute). Heart rate was faster in
      transplant patients than in control subjects, with much less heart rate
      variability (P < .0001). Spectral analysis of blood pressure variability revealed
      no difference in total power for either systolic or diastolic pressure, but
      transplant patients had less low-frequency (0 to 0.15 Hz) harmonic spectral power
      in both systolic (P < .01) and diastolic (P < .03) pressure and more high
      frequency power (0.15 to 0.5 Hz) in diastolic pressure than control subjects. The
      ratio of high-frequency power in diastolic relative to systolic pressure was
      consistently higher (P < .0001) in the transplant patients (0.29 to 0.51) than in
      control subjects (0.11 to 0.13). The slope of the fractal component of systolic
      pressure was approximately 1.8 in both transplant patients and control subjects.
      This was greater than the slope for heart rate variability (approximately 1.1 in
      control subjects). These data provide clear evidence of independence of the
      fractal component of heart rate and blood pressure variabilities in both
      transplant patients and control subjects. The heart rate component of the
      arterial baroreflex minimized high-frequency diastolic pressure changes while
      contributing to low-frequency variations in both systolic and diastolic
      pressures.

PMID- 7721411
TI  - Common carotid artery stiffness and patterns of left ventricular hypertrophy in
      hypertensive patients.
AB  - The aim of this study was to determine the relationship between the lumen
      diameter and function of the common carotid artery, a vessel representative of
      the capacitance portion of the circulation, and the different patterns of left
      ventricular hypertrophy in uncomplicated essential hypertensive patients. Carotid
      luminal diastolic cross-sectional area, distensibility, and compliance were
      derived from measurements by a high-definition echotracking system. Left
      ventricular dimensions were from echocardiography. The 86 hypertensive patients
      included 31 who had never been treated (group 1), 31 in whom treatment had been
      stopped for at least 2 weeks (group 2), and 24 treated patients (group 3). In
      multivariate analysis of the population as a whole, the following relations were
      statistically independent of age, blood pressure, gender, and group: Left
      ventricular end-diastolic volume index was positively correlated to carotid
      luminal cross-sectional area (r = .46, P < .0001) and compliance (r = .47, P <
      .0001); left ventricular mean wall thickness and mass-volume ratio were
      negatively correlated to distensibility (r = -.68, P < .0001; r = -.46, P <
      .0001, respectively) and compliance (r = -.40, P < .0001; r = -.37; P < .001,
      respectively); and left ventricular mass index was positively correlated to
      luminal cross-sectional area (r = .23, P < .02) and negatively to distensibility
      (r = -.26, P < .01). These results indicate that geometric and functional changes
      in the common carotid artery accompany geometric changes in the left ventricle.
      More specifically, they suggest that a reduction in distensibility paralleled
      cardiac concentric hypertrophy and remodeling, whereas an increase in arterial
      volume paralleled increased left ventricular cavity size.

PMID- 7721412
TI  - Genetic contamination of inbred Dahl rats from Harlan Sprague Dawley.

PMID- 7721413
TI  - The renal medulla and hypertension.
AB  - We review evidence supporting the conclusion that renal dysfunction underlies the
      development of all forms of hypertension in humans and experimental animals.
      Indexes of global renal function are generally normal in the early stages of most
      genetic forms of hypertension, but renal function is clearly impaired in long
      established hypertension. Studies in our laboratory over the past decade
      summarized below have established that the renal medulla plays an important role
      in sodium and water homeostasis and in the long-term control of arterial
      pressure. Development of implanted optical fibers for measurement of cortical and
      medullary blood flows with laser-Doppler flowmetry and techniques for delivery of
      vasoactive compounds into the medullary interstitial space enabled us to examine
      determinants of medullary flow (nitric oxide, atrial natriuretic peptides,
      kinins, eicosanoids, vasopressin, renal sympathetic nerves, etc). We have shown
      in spontaneously hypertensive rats that the initial changes of renal function
      begin as a reduction of medullary blood flow in the absence of changes of
      cortical flow. Long-term medullary interstitial infusion of captopril, which
      preferentially increased medullary blood flow, resulted in a lowering of arterial
      pressure. In normal Sprague-Dawley rats, selective reduction of medullary flow
      with medullary interstitial or intravenous infusion of small amounts of NG-nitro
      L-arginine methyl ester resulted in hypertension. These and other studies we
      review show that although blood flow to the inner renal medulla comprises less
      than 1% of the total renal blood flow, changes in flow to this region can have a
      major effect on sodium and water homeostasis and on the long-term control of
      arterial blood pressure.

PMID- 7721415
TI  - Fra-1, a Fos gene family member that activates atrial natriuretic peptide gene
      transcription.
AB  - Previous studies suggested that individual components of the activator protein 1
      (AP-1) complex behave in a highly idiosyncratic fashion at the level of the human
      atrial natriuretic peptide (ANP) gene promoter. ANP gene transcription is
      activated by c-jun and is generally suppressed by c-fos. In the present study,
      fra-1, a close relative of the c-fos gene product in terms of its structure and
      functional activity, behaved like fos in cardiac atriocytes, effecting an
      approximately 50% reduction in c-jun-activatable expression of a human ANP
      chloramphenicol acetyltransferase (CAT) reporter. In cardiac ventriculocytes,
      however, fra-1 effected a synergistic amplification of the c-jun response (a 2.5
      fold increase over c-jun alone). In atrial cells, fos-like proteins were not
      uniformly inhibitory in that a carboxy terminal deletion mutant of c-fos
      activated a human ANP-CAT reporter in the atriocyte cultures. Finally, using a
      series of domain-swap mutations in the fos/fra structural sequences, we showed
      that sequences at both the amino and the carboxy termini are required to realize
      the full fra-1-dependent stimulatory effect as well as the c-fos-dependent
      inhibition of ANP gene transcription. These findings suggest considerable
      heterogeneity in the response of the ANP promoter to different components of the
      AP-1 complex. Such heterogeneity may serve to broaden the range of biological
      responses available to this promoter as the cardiac cell attempts to adapt to
      perturbations in the extracellular environment.

PMID- 7721414
TI  - Expression of angiotensin-converting enzyme in renovascular hypertensive rat
      kidney.
AB  - We hypothesized that the gene expression of angiotensinogen, angiotensin
      converting enzyme, and angiotensin II type 1 receptor, in addition to renin, is
      increased in kidneys after renal artery stenosis. Two-kidney, one clip
      renovascular hypertension was initiated in Sprague-Dawley rats by clipping of the
      left renal artery; control rats were sham operated. Blood pressure was not
      changed for the first 2 days after clipping but was elevated on day 4 (mean
      arterial pressure, 104 +/- 4 versus 87 +/- 2 mm Hg in sham-operated control rats,
      P < .002) and increased further during the next 24 days. Rats were killed 2, 4,
      7, 14, and 28 days after clipping or sham operation, and poly(A)(+)-purified
      renal cortical RNA was analyzed by Northern blotting. Autoradiographs were
      quantitated by densitometry and normalized for the expression of a housekeeping
      gene. Renin expression was increased in the clipped kidney (by 149% on day 2) and
      decreased in the nonclipped kidney (by 82% on day 2), compared with kidneys of
      control rats. Expression of the angiotensin-converting enzyme was increased in
      clipped kidneys from the first day after clipping (158%) and throughout the
      experiment (66% on day 28), but was unchanged or slightly decreased in nonclipped
      kidneys. Angiotensinogen mRNA showed little change. Angiotensin II type 1
      receptor expression was decreased in nonclipped kidneys but unchanged during the
      first 7 days in clipped kidneys. Our results show that components of the renin
      angiotensin system other than renin are also differentially expressed in clipped
      kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721416
TI  - Characterization and functional analysis of the rat endothelin-1 promoter.
AB  - To define the molecular mechanisms of endothelin-1 (ET-1) gene regulation, we
      cloned, sequenced, and characterized the rat ET-1 promoter. A sequence consisting
      of the first 1329 bp of the rat ET-1 promoter was investigated in greater detail.
      Sequence analysis identified putative binding sites for a number of
      transcriptional factors that may be involved in ET-1 gene regulation. Several of
      these factors have been proposed earlier to be involved in cell-specific gene
      regulation and may be responsible for directing ET-1 expression in vivo. For
      functional analysis of the ET-1 promoter, we generated a reporter gene construct
      using luciferase as reporter gene under control of the promoter fragment
      isolated. The construct was transfected transiently into bovine aortic
      endothelial cells, and luciferase expression was evaluated. The results indicated
      that the promoter segment used showed high expression in endothelial cells
      comparable to that induced by viral promoters. Since ET-1 is regulated by a
      number of vasoactive substances, we studied the effect of angiotensin II on
      endothelin transcription. We could demonstrate a dose-dependent transcriptional
      activation of ET-1 transcription by angiotensin.

PMID- 7721417
TI  - Angiotensinogen gene and blood pressure in the Japanese population.
AB  - A molecular variant of the angiotensinogen gene with threonine instead of
      methionine at position 235 (ie, with M235T polymorphism) has been shown to be
      associated with essential hypertension in Caucasian populations. The purpose of
      the present study was to assess whether the M235T polymorphism was associated
      with essential hypertension in the Japanese population. The study population
      consisted of 347 subjects selected in our outpatient clinic. The clinical data
      included in the analyses were sex, age, body mass index, cholesterol level,
      genotype of the angiotensinogen gene, genotype of the angiotensin-converting
      enzyme gene, and systolic and diastolic blood pressure. Multiple regression
      analysis revealed that only body mass index was a predictor of both diastolic and
      systolic blood pressure in these 347 subjects, but the genotype of the
      angiotensinogen gene was identified as a predictor of both diastolic and systolic
      blood pressure in a subpopulation less than 50 years of age. However, in a
      subpopulation more than 50 years of age, body mass index was the only predictor
      of both systolic and diastolic blood pressure. Of the 347 subjects, 189 had a
      technically excellent echocardiogram at the initial observation period. Multiple
      regression analysis revealed that sex, body mass index, diastolic blood pressure,
      and genotype of the angiotensin-converting enzyme gene were predictors of left
      ventricular mass. Although subjects with the TT angiotensinogen genotype had
      significantly greater left ventricular mass than those with either the TM or the
      MM genotype, the effects of the genotype of the angiotensinogen gene on left
      ventricular mass were mainly due to effects on blood pressure.

PMID- 7721418
TI  - Mutational inactivation of the catalytic domain of guanylate cyclase-A receptor.
AB  - Guanylate cyclase-A, the receptor for atrial natriuretic factor, contains a
      protein kinase-like domain and a catalytic domain in the intracellular region. To
      investigate the active site (the catalytic cavity) of guanylate cyclase-A, we
      amplified the catalytic domain plus three amino acids from the kinase-like domain
      of guanylate cyclase-A (GC-c) with polymerase chain reaction (PCR) and expressed
      it in Escherichia coli. During the screening of the PCR-cloned gene products with
      guanylate cyclase assay, a mutant that lacks enzyme activity was identified.
      Results of cDNA sequencing revealed that Leu 817 was replaced by an Arg residue
      in the mutated protein. The mutated GC-c bound to GTP-agarose as well as the wild
      type protein, indicating that the binding capability of mutated GC-c to GTP is
      not significantly affected by the Arg substitution. Gel-filtration column
      chromatography showed that, like the wild-type GC-c, the mutated protein also
      formed a high-molecular-weight complex. Since mutation of Leu 817 to Arg
      abolishes the catalytic activity, Leu 817 is likely located near the active site
      of guanylate cyclase-A. These results demonstrate that the carboxyl fragment of
      guanylate cyclase-A is an ideal system for studying the active site of guanylate
      cyclase-A.

PMID- 7721419
TI  - Comparison of effects of angiotensin I-converting enzyme inhibition and beta
      blockade for 2 years on function of small arteries from hypertensive patients.
AB  - The effect of treatment with two different antihypertensive agents on the
      function of small arteries from 17 patients with essential hypertension randomly
      assigned to receive either the angiotensin I-converting enzyme inhibitor
      cilazapril or the beta-blocker atenolol was investigated. Subcutaneous small
      arteries obtained from gluteal fat biopsies were studied on a wire myograph
      before treatment and at 1 and 2 years of treatment. Blood pressure was mildly
      elevated in both groups of patients (mean, 150/100 mm Hg) and was well controlled
      throughout the 2 years of treatment (mean, 130/85 mm Hg). We previously reported,
      in arteries from patients treated with cilazapril, an improvement at 1 year of
      treatment of the vasoconstrictor effect of endothelin-1, which had been
      significantly attenuated in the untreated hypertensive patients compared with
      normotensive subjects. After 2 years of treatment, this normalization of
      endothelin-1 response was still present in small arteries of patients treated
      with the angiotensin I-converting enzyme inhibitor, whereas in patients treated
      with atenolol, responses were still unchanged after 2 years of treatment.
      Endothelial function was tested by examining the response of norepinephrine
      precontracted arteries to acetylcholine. Untreated hypertensive patients
      exhibited a slightly but significantly blunted vasorelaxation in response to 10
      mumol/L acetylcholine compared with normotensive subjects. After 1 and 2 years of
      effective antihypertensive treatment, cilazapril-treated patients exhibited
      responses to acetylcholine that were not different from those of normotensive
      subjects, whereas atenolol-treated patients still had impaired
      responses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721420
TI  - Endogenous human renin expression and promoter activity in CALU-6, a pulmonary
      carcinoma cell line.
AB  - We have previously reported that transgenic mice containing the human renin gene
      express high levels of human renin mRNA in the lung. We show in this report that
      human renin expression in two lines of transgenic mice is developmentally
      regulated. Human renin expression is not evident in the transgenic mouse lung at
      15.5 days of gestation, is detectable at 17.5 days of gestation, peaks around
      birth, and remains elevated into adulthood. In situ hybridization of mouse fetal
      lung samples at 18.5 days of gestation revealed that human renin was exclusively
      expressed in pulmonary type II epithelial cells. A survey of the medical
      literature revealed a number of clinical cases in which hypertension was caused
      by renin-secreting pulmonary tumors and a fairly widespread occurrence of
      immunoreactive renin in banked pulmonary tumors of diverse origin. This prompted
      us to examine a number of pulmonary tumor cell lines to determine whether they
      express human renin mRNA. One pulmonary carcinoma cell line, CALU-6, expressed
      human renin mRNA endogenously. Human renin expression in these cells was induced
      approximately 100-fold after treatment with forskolin, 8-bromoadenosine 3':5'
      cyclic monophosphate, or N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate.
      Transfection analysis of human renin promoter-luciferase fusion constructs
      revealed the presence of cell-specific positive and negative regulatory elements
      in the human renin 5'-flanking DNA. This cell line is the only immortalized human
      cell line that expresses high levels of endogenous human renin mRNA and should
      provide an excellent tool for studying the regulation of human renin expression
      in vitro.

PMID- 7721421
TI  - Muscle delivery of human kallikrein gene reduces blood pressure in hypertensive
      rats.
AB  - We recently found that transgenic mice expressing human tissue kallikrein develop
      sustained hypotension. The result suggests that a continuous supply of human
      tissue kallikrein could have a prolonged effect on blood pressure reduction. In
      the present study, we investigated the potential of using human tissue kallikrein
      for gene therapy by injecting a kallikrein gene construct into the skeletal
      muscle of spontaneously hypertensive rats. Expression of the human tissue
      kallikrein messenger RNA in spontaneously hypertensive rats was identified by
      reverse transcription-polymerase chain reaction with Southern blot. Human tissue
      kallikrein was detected in the injected animals by an enzyme-linked immunosorbent
      assay. Injection of the human kallikrein gene into spontaneously hypertensive
      rats caused a significant reduction of systemic blood pressure, ranging from 15
      to 26 mm Hg, compared with the control group. The differences were significant 1
      week after the injection and continued for more than 2 months. Blood pressure
      reduction could be reversed after the administration of the bradykinin antagonist
      Hoe 140. The results indicate that somatic delivery of the human tissue
      kallikrein gene induces a sustained reduction of systemic blood pressure in
      spontaneously hypertensive rats. The present study raises the possibility of
      applying kallikrein gene therapy to the treatment of human hypertensive diseases.

PMID- 7721422
TI  - Transcriptional regulation of the mouse angiotensin II type 2 receptor gene.
AB  - The promoter region of the mouse angiotensin II type 2 receptor gene was cloned,
      and the nucleotide sequences were determined. A computer homology search for a
      1.5-kb promoter region showed that there are several consensus cis DNA elements
      such as C/EBP, NF-IL6, and AP-1 in this region. Primer extension experiments
      showed that there are two transcription initiation sites 16 bp apart in the mouse
      type 2 receptor gene. Deletion mutants of this 1.5-kb segment were prepared and
      fused to a luciferase reporter gene. These type 2 receptor promoter-luciferase
      constructs were introduced into PC12W cells, which are from a pheochromocytoma
      cell line expressing the type 2 receptor, and luciferase activity was measured.
      It showed that a DNA segment between nucleotides -1497 and -874 suppresses the
      promoter activity of the type 2 receptor gene and that a DNA segment between
      nucleotides -47 and +56 is important for the basal promoter activity of the type
      2 receptor gene. This proximal segment showed very weak promoter activity when
      introduced into vascular smooth muscle cells. Gel mobility shift assay with
      nuclear extracts from PC12W cells showed the presence of three DNA binding
      proteins that bound to a DNA probe between nucleotides -47 and +8. One DNA
      binding protein was only very weakly expressed in nuclear extracts from vascular
      smooth muscle cells, which do not express the type 2 receptor. Two other DNA
      binding proteins were not observed in nuclear extracts from vascular smooth
      muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721423
TI  - Mapping of G protein coupling sites of the angiotensin II type 1 receptor.
AB  - Angiotensin II type 1 (AT1) receptors have been identified in a wide variety of
      tissues, including the kidney, liver, adrenal gland, cardiovascular system, and
      brain. AT1 receptors also mediate complex signaling mechanisms that elicit a
      diversity of specific physiological effects. The rat AT1A receptor has seven
      transmembrane domains and couples with three distinct G proteins: Gq, Gi, and Go.
      But it is unknown which domains of AT1A couple with and activate each type of G
      protein. To identify the domains responsible for the activation of various types
      of G protein, we studied the effect of five different synthetic peptides
      representing different domains of cytosolic segments of the rat AT1A receptor on
      the binding of the 35S-labeled stable analogue of GTP, GTP gamma S. Peptides P-3,
      which is located in the N-terminal region of the putative third intracellular
      loop of AT1A (residues 216 through 230), and P-5 (residues 306 through 320),
      corresponding to the N-terminal region of the C-terminal tail, were found to
      activate purified Gi1, Gi2, and Go proteins. These results indicate that not only
      the third cytosolic loop but also the C-terminal cytosolic domain of AT1A is
      important for Gi1, Gi2, and Go protein coupling and activation.

PMID- 7721424
TI  - Decreased dihydropyridine receptor number in hypertensive rat vascular muscle
      cells.
AB  - To further investigate the altered function of Ca2+ channels in vascular muscle
      cells in hypertension, a novel fluorescently labeled dihydropyridine was used
      with ultrahigh-sensitivity photometry to study dihydropyridine binding sites on
      the surface membrane of living vascular muscle cells from stroke-prone
      spontaneously hypertensive rats and their normotensive controls. Fluorescent
      nitrobenzoxadiazol-6-dihydropyridine in concentrations of 1 to 100 nmol/L bound
      specifically to vascular muscle cells' Ca2+ channels, and was displaced by the
      unlabeled dihydropyridine analogue or nisoldipine (10 mumol/L). Stroke-prone
      spontaneously hypertensive rat vascular muscle cells showed significantly
      decreased binding of nitrobenzoxadiazol-6-dihydropyridine compared with
      normotensive National Institutes of Health rats. Decreased binding of
      dihydropyridine by vascular muscle cells from stroke-prone spontaneously
      hypertensive rats (cells that in other studies show increased Ca2+ channel
      function) indicates a change in channel regulation that is possibly due to a
      deficiency in the inactivation mechanism, consistent with our earlier
      electrophysiological studies reporting deficiencies in Ca(2+)-dependent
      inactivation in genetic hypertension. These data demonstrate decreased numbers of
      localized sites of dihydropyridine binding on the sarcolemma of living vascular
      muscle cells, and support the hypothesis that Ca2+ channel alterations may
      significantly contribute to the molecular etiology of genetic hypertension.

PMID- 7721425
TI  - Endothelin receptor subtypes in small arteries. Studies with FR139317 and
      bosentan.
AB  - We studied the effects of the selective endothelin A receptor antagonist FR139317
      and the combined endothelin A/endothelin B receptor antagonist bosentan in rat
      mesenteric arteries by using a video dimension analyzer. In endothelium-denuded
      arteries, increasing concentrations of endothelin-1 evoked a biphasic
      vasoconstriction. The first phase was observed at low concentrations (10(-16) to
      10(-11) mol/L) of endothelin-1 and was relatively weak. However, the contractions
      characterizing the second phase, which occurred at higher concentrations (10(-10)
      to 3 x 10(-8) mol/L) of endothelin-1, were much stronger. FR139317 concentration
      dependently shifted the second phase of the endothelin-1-induced contraction
      curve to the right without affecting the first phase. In contrast, bosentan
      inhibited both the first and the second phase. Even after the blockade of
      endothelin A receptor, increasing concentrations of the endothelin B receptor
      agonists endothelin-3 and sarafotoxin S6c still induced small contractions.
      Maximal contractions induced by single-bolus extraluminal application of
      endothelin-3 (10(-9) mol/L) or sarafotoxin S6c (3 x 10(-8) mol/L) were markedly
      more pronounced than responses induced by cumulative concentrations, suggesting
      endothelin B receptor downregulation upon repeated and sustained activation. The
      response induced by a single bolus of endothelin-3 (10(-9) mol/L) was antagonized
      by bosentan but not by FR139317, confirming that endothelin B receptors were
      involved. In endothelium-intact arteries half-maximally precontracted with
      norepinephrine, bosentan but not FR139317 inhibited the relaxations induced by
      intraluminally applied endothelin-3. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721426
TI  - Endothelin-1 enhances nitric oxide-induced cytotoxicity in vascular smooth
      muscle.
AB  - Prolonged incubation with 1 nmol/L interleukin-1 induced high levels of nitric
      oxide release and cytotoxicity in vascular smooth muscle cells. NG-Monomethyl-L
      arginine, an inhibitor of nitric oxide synthesis, inhibited interleukin-1-induced
      cytotoxicity at a concentration of 3 mmol/L. Furthermore, prolonged incubation
      with 0.1 mmol/L sodium nitroprusside, a nitric oxide donor, also induced
      cytotoxicity. On the other hand, endothelin-1 at concentrations from 10(-10) to
      10(-7) mol/L induced a concentration-dependent enhancement of cytotoxicity
      induced by interleukin-1. However, endothelin-1 did not affect interleukin-1
      induced nitric oxide production. Coculture study of vascular smooth muscle cells
      and endothelial cells without direct cell contact revealed that incubation for 72
      hours with interleukin-1 induced high levels of nitric oxide release from
      cocultured vascular smooth muscle cells to the same degree as release from
      vascular smooth muscle cells alone. However, interleukin-1-induced cytotoxicity
      was more enhanced in cocultured vascular smooth muscle cells than in vascular
      smooth muscle cells alone. Furthermore, coincubation with 20 nmol/L BQ-485, an
      antagonist of one type of endothelin receptor (ETA), prevented the enhancement of
      interleukin-1-induced cytotoxicity in cocultured vascular smooth muscle cells.
      These findings suggest that endothelin-1 secreted from endothelial cells may
      enhance nitric oxide-induced cytotoxicity by means of the ETA receptor in
      vascular smooth muscle cells.

PMID- 7721427
TI  - Influence of endothelium on cultured vascular smooth muscle cell proliferation.
AB  - The endothelium exerts a large influence on the underlying vascular smooth
      muscle, not only by the release of both contracting and relaxing factors but also
      by its ability to synthesize a large number of molecules that influence vascular
      smooth muscle growth. In addition to well-characterized growth promoters or
      growth inhibitors, some endothelium-derived factors, originally described as
      vasoactive compounds, seem to possess growth-regulatory properties. The
      vasoconstrictor endothelin-1 elicited a dose-dependent increase of cultured
      vascular smooth muscle cell DNA synthesis with a maximal effect of 57 +/- 14%
      over basal levels, whereas vasodilators such as prostacyclin, sodium
      nitroprusside, and 8-bromoguanosine 3':5'-cyclic monophosphate reduced DNA
      synthesis by 19 +/- 5%, 22 +/- 2%, and 31 +/- 3%, respectively. Medium
      conditioned by cultured bovine aortic endothelial cells markedly stimulated both
      DNA synthesis and proliferation of smooth muscle cells. When medium was
      conditioned in the presence of the endothelin-converting enzyme inhibitor
      phosphoramidon, the mitogenic effect was significantly reduced, thus indicating a
      role for endothelin in the stimulation of smooth muscle cell growth by
      endothelial cells. However, when both cell types were maintained in a coculture
      system, a 13 +/- 2% decrease of DNA synthesis was observed in smooth muscle
      cultures. The addition of the nitric oxide synthase inhibitor N omega-nitro-L
      arginine methyl ester, the cyclooxygenase inhibitor indomethacin, or both during
      the coculture period did not revert the antiproliferative effect of endothelial
      cells in coculture, thereby indicating it is not likely due to these unstable
      endothelium-derived vasorelaxant molecules.

PMID- 7721428
TI  - Calcium- and protein kinase C-dependent basal tone in the aorta of hypertensive
      rats.
AB  - We examined the regulatory influence of nitric oxide on development of calcium-
      and protein kinase C-dependent basal tone in rings of thoracic aortas from rats
      with aortic coarctation-induced hypertension and from normotensive controls.
      Aortic rings from hypertensive rats but not those from normotensive rats, bathed
      in Krebs' bicarbonate buffer and subjected to 2 g of passive stretch, were
      relaxed by removal of calcium from the buffer and by the protein kinase C
      inhibitors staurosporine and calphostin C. Protein kinase C activity was much
      greater in homogenates of aortae from hypertensive rats than in those from
      normotensive controls (2124 +/- 785 versus 608 +/- 73 pmol.min-1.mg protein-1,
      respectively). Relaxant responses to removal of calcium and to staurosporine were
      greater in aortic rings rubbed to remove the vascular endothelium than in
      endothelium-intact rings (-1.07 +/- 0.12 versus -0.70 +/- 0.10 g tension/mg
      tissue, respectively, for calcium removal and -1.10 +/- 0.12 versus -0.65 +/-
      0.08 g tension/mg tissue, respectively, for staurosporine). Treatment with an
      inhibitor of nitric oxide synthesis increased calcium-dependent tone in both
      intact and endothelium-denuded aortic rings from hypertensive rats. Conversely,
      the administration of sodium nitroprusside or L-arginine reversed tone in both
      intact and denuded aortic rings from hypertensive rats, but acetylcholine
      reversed tone only in intact rings. The relaxant effects of these agents were
      paralleled by increases in cyclic guanosine monophosphate in aortic tissue. We
      conclude that aortic rings from rats with aortic coarctation-induced hypertension
      display calcium-dependent, protein kinase C-mediated tone in the absence of
      exogenous vasoconstrictors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721429
TI  - Shear stress-induced dilation is attenuated in skeletal muscle arterioles of
      hypertensive rats.
AB  - Hypertension is thought to alter many of the functions of the vascular
      endothelium. The present study examines whether shear stress-induced endothelium
      dependent skeletal muscle arteriolar dilation is compromised in genetically
      hypertensive rats. Changes in the diameter of isolated, perfused arterioles
      (approximately 60 microns) from gracilis muscles of 12-week-old normotensive
      Wistar rats (NWR) and spontaneously hypertensive rats (SHR) were investigated. At
      a constant perfusion pressure (80 mm Hg), the active diameter of NWR and SHR
      arterioles was 57.1 +/- 2.0 and 50.9 +/- 3.5 microns, respectively (mean +/-
      SEM), while the passive diameter (in Ca(2+)-free solution) was 113.2 +/- 3.1 and
      100.6 +/- 2.9 microns, respectively. Increases in wall shear stress (from 0 to
      100 dyne/cm2) elicited by increases in perfusate flow (from 0 to 25 microL/min)
      resulted in marked increases in the diameter of NWR arterioles, but such
      increases produced substantially smaller dilations in SHR arterioles (43.0 versus
      18.9 microns). The prostaglandin synthesis inhibitor indomethacin (10(-5) mol/L)
      significantly attenuated the shear stress-induced dilations in both strains of
      rats. In contrast, the nitric oxide synthase inhibitor N omega-nitro-L-arginine
      (10(-4) mol/L) significantly shifted the shear stress-diameter curve to the right
      in vessels from NWR (by 50 dyne/cm2) but not in those from SHR. Thus, in gracilis
      muscle arterioles of SHR, the reduced dilation to increases in shear stress seems
      to be due to the lack of nitric oxide synthesis and/or release in response to
      shear stress.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721430
TI  - Deoxycorticosterone acetate plus salt induces overexpression of vascular
      endothelin-1 and severe vascular hypertrophy in spontaneously hypertensive rats.
AB  - Endothelin-1 gene expression is enhanced in the aorta and mesenteric arteries,
      and possibly other vessels, of deoxycorticosterone acetate (DOCA)-salt
      hypertensive rats. In contrast, endothelin-1 gene expression is normal or reduced
      in spontaneously hypertensive rats (SHR). Severe vascular hypertrophy is present
      in DOCA-salt hypertensive rats but not in SHR. In this study we investigated
      whether treatment of SHR with DOCA and salt would result in enhanced endothelin-1
      expression and at the same time in severe vascular hypertrophy. Increased
      abundance of endothelin-1 mRNA was found in the aorta and the mesenteric arterial
      bed of SHR treated simultaneously with DOCA and salt but not when rats were
      treated with either separately. The wet weight of the aorta and of the mesenteric
      arterial bed, media thickness, media cross-sectional area, and media-to-lumen
      ratio of mesenteric small arteries of DOCA-salt-treated SHR were exaggerated
      beyond what could be explained by the elevation of blood pressure, relative to
      SHR treated with salt or with DOCA, which did not overexpress vascular endothelin
      1. In conclusion, SHR may exhibit enhanced expression of the endothelin-1 gene in
      blood vessels when treated with DOCA and salt, and associated with this there is
      severe vascular hypertrophy. These data support the hypothesis of a role of
      endothelin-1 in vascular hypertrophy.

PMID- 7721431
TI  - Fatty acids enhance vascular alpha-adrenergic sensitivity.
AB  - Hypertensive patients are heavier and have a more centralized body fat
      distribution, which is associated with risk factor clustering and resistance to
      insulin's actions, including suppression of plasma nonesterified fatty acids. We
      postulated that abnormalities of nonesterified fatty acids contribute to the
      increased vascular alpha-adrenergic reactivity and tone observed in our previous
      studies of obese hypertensive subjects. To test this hypothesis, in two separate
      protocols 10% Intralipid was infused into a dorsal hand vein with heparin to
      activate lipoprotein lipase and raise fatty acid levels locally. In protocol 1,
      the effects of Intralipid/heparin compared with those of 5% dextrose/heparin on
      dorsal hand vein sensitivity to phenylephrine were assessed by use of the linear
      variable differential transformer technique in 8 normotensive subjects. In
      protocol 2, the effects of Intralipid/heparin were compared with those of
      saline/heparin on hand vein responses to both phenylephrine and angiotensin II in
      11 normotensive African American women. Intralipid/heparin reduced the dose of
      phenylephrine required to produce 50% of the maximal venoconstrictor response
      from 582 to 137 ng/min (compared with dextrose/heparin, P < .01) in protocol 1
      and from 293 to 137 ng/min (compared with saline/heparin, P < .01) in protocol 2.
      Intralipid/heparin did not significantly alter hand vein responses to angiotensin
      compared with saline/heparin. These data suggest that abnormalities of
      nonesterified fatty acids in obese hypertensive patients with risk factor
      clustering may contribute to their increased neurovascular tone.

PMID- 7721432
TI  - Insulin attenuates norepinephrine-induced venoconstriction. An ultrasonographic
      study.
AB  - To directly assess insulin-related venomotor changes objectively and
      quantitatively, we used a modified ultrasonographic technique to measure venous
      diameter. Ten healthy men and women were studied by use of an Acuson 128 XP
      ultrasonograph with a linear 7.5-MHz ultrasonographic transducer (sensitivity, +/
      0.1 mm). Venous diameter was measured with the arm kept at 30 degrees elevation
      and with a pneumatic cuff above the elbow inflated at 40 mm Hg for the last 2
      minutes of each 5-minute observation period. Norepinephrine was infused at
      incremental concentrations of 12.5, 25, 50, and 100 ng/min (75, 150, 300, and 600
      pmol/min, respectively) for 5 minutes each. Maximal venoconstriction was achieved
      by the dose of 100 ng/min norepinephrine, which was then combined with insulin
      doses of 8, 16, 24, and 32 microU/min (60, 120, 180, and 230 fmol/min,
      respectively) for 5 minutes each. In six different subjects, methylene blue, an
      inhibitor of guanylate cyclase, was infused simultaneously with 32 microU/min
      insulin and 100 ng/min norepinephrine. Mean resting diameter of the vein (1.8 +/-
      0.6 mm [mean +/- SD]) increased (to 3.0 +/- 1.0 mm) after cuff inflation.
      Incremental doses of norepinephrine caused highly reproducible dose-dependent
      decrease in venous diameter (to 1.8 +/- 0.6 mm, P < .001). Incremental doses of
      insulin, when combined with the maximum dose of norepinephrine, caused highly
      reproducible dose-dependent increases in mean venous diameter (P < .001) compared
      with norepinephrine alone. Methylene blue, which had no independent effect on
      venous diameter, inhibited the venodilator effect of insulin (P < .05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7721433
TI  - Lead increases aldosterone production by rat adrenal cells.
AB  - Exposure to lead has been postulated to contribute to elevated blood pressure in
      humans and has been shown to raise blood pressure in animals. The mechanism of
      action of lead on blood pressure is unknown. We fed lead to rats in their
      drinking water and then examined the production of aldosterone by their adrenal
      cells in vitro. We also measured excretion of aldosterone and corticosterone by
      intact rats stimulated with corticotropin, with and without lead treatment. At a
      dose (273 ppm) that raised blood levels to 30 to 40 micrograms/dL, comparable to
      blood levels in exposed humans, lead induced increased aldosterone secretion in
      vitro and in vivo. The effect of lead was most evident when cells or animals were
      stimulated with aldosterone secretagogues. Experiments in vitro indicate that
      exposure to lead in vivo increases activity of one or more steps in the late
      pathway of aldosterone biosynthesis. The results suggest that the hypertensive
      effect of lead involves relative hyperaldosteronism and may be most evident when
      secretion of this hormone is stimulated.

PMID- 7721434
TI  - Mechanisms of adrenomedullin-induced vasodilation in the rat kidney.
AB  - To explore the mechanisms of adrenomedullin-induced vasorelaxation, we tested the
      effects of adrenomedullin on renal function in rats in vivo and measured the
      release of endothelium-derived nitric oxide from isolated perfused rat kidney
      (using a chemiluminescence assay) and the diameters of the glomerular arterioles
      in the hydronephrotic kidney. Adrenomedullin decreased blood pressure in a dose
      dependent manner (3 nmol/kg: -29 +/- 2% [SEM]; P < .01) and slightly increased
      the glomerular filtration rate and urinary sodium excretion (+108%; P < .05).
      These changes were associated with significant increases in urinary excretion of
      cyclic AMP (+54%; P < .05). Adrenomedullin decreased renal vascular resistance
      (10(-7) mol/L adrenomedullin: -41 +/- 2%; P < .001) and increased release of
      nitric oxide (+5.1 +/- 0.7 fmol/min per gram kidney weight; P < .001) in the
      isolated kidney. This increase in nitric oxide release was abolished by the
      inhibitor NG-monomethyl-L-arginine, and it also reversed the decrease in renal
      vascular resistance seen with adrenomedullin. Renal responses of
      deoxycorticosterone acetate-salt hypertensive rats to adrenomedullin were
      significantly smaller than those of control rats for both release of nitric oxide
      (10(-7) mol/L adrenomedullin: +0.8 +/- 0.2 fmol/min per gram kidney weight; P <
      .01 versus control) and renal vasodilation (-28 +/- 6%; P < .05).
      Videomicroscopic analysis revealed that adrenomedullin increased the diameters of
      both afferent and efferent arterioles (3 nmol/kg: +11%; P < .05). Thus,
      adrenomedullin-induced renal vasodilation is partially endothelium dependent and
      is attenuated in deoxycorticosterone acetate-salt hypertension, probably due to
      endothelial damage.

PMID- 7721435
TI  - Endothelium-derived constricting factor in renovascular hypertension.
AB  - We have reported that in two-kidney, one clip hypertensive rats, renal perfusion
      is maintained by a balance between the vasodilator endothelium-derived nitric
      oxide and the vasoconstrictor angiotensin II. Others have suggested that
      endothelium-derived constricting factor, reported to be thromboxane A2 and/or
      endoperoxide, contributes to increased blood pressure in angiotensin II-dependent
      hypertension. We hypothesized that in angiotensin II-dependent two-kidney, one
      clip hypertension, endothelium-derived constricting factor contributes to
      vasoconstriction of the clipped kidney following nitric oxide synthesis
      inhibition. Using radioactive microspheres, we studied renal blood flow to the
      stenotic kidney of two-kidney, one clip hypertensive rats 4 weeks after clipping.
      The influence of nitric oxide on systemic and renal hemodynamics was evaluated by
      determining the response to nitric oxide synthesis inhibition using 10 mg/kg N
      omega-nitro-L-arginine methyl ester in these rats, which were either not treated
      (n = 8) or treated (n = 8) with 4 mg/kg of the constricting factor receptor
      antagonist BMS 180,291. Mean basal blood pressure in rats was 167 +/- 9 mm Hg
      (mean +/- SEM). N omega-Nitro-L-arginine methyl ester increased blood pressure by
      35 +/- 7 mm Hg (P < .001). In the clipped kidney, N omega-nitro-L-arginine methyl
      ester decreased renal blood flow by 40% (from 4.5 +/- 0.9 to 2.7 +/- 0.6 mL.min
      1.g kidney-1; P < .01) and increased renal vascular resistance by 100% (from 51.9
      +/- 9.6 to 105.0 +/- 19.2 mm Hg.mL-1.min-1.g kidney-1; P < .005).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7721436
TI  - Brain 'ouabain,' sodium, and arterial baroreflex in spontaneously hypertensive
      rats.
AB  - To assess the possible role of brain "ouabain" in modulating arterial baroreflex
      function in salt-sensitive hypertension, arterial baroreflex control of renal
      sympathetic nerve activity and heart rate was evaluated in conscious
      spontaneously hypertensive rats and compared with that in Wistar-Kyoto rats. A
      regular sodium or high sodium diet was provided from 5 to 9 weeks of age, with
      intracerebroventricular infusion of antibody Fab fragments, which bind
      ouabainlike substances with high affinity, or, as control, nonspecific gamma
      globulins (200 micrograms.12 microL-1.d-1 for both). Baroreflex function was
      assessed by plotting changes in renal sympathetic nerve activity or heart rate
      against changes in mean arterial pressure by phenylephrine and nitroprusside. In
      control Wistar-Kyoto rats, high sodium intake did not increase resting blood
      pressure but sensitized baroreflex control of renal sympathetic nerve activity.
      In control spontaneously hypertensive rats, high sodium intake significantly
      increased blood pressure but did not enhance renal sympathetic nerve activity
      responses. However, in spontaneously hypertensive rats given high sodium diets
      and treated with Fab fragments, blood pressure did not increase and the
      baroreflex control of renal sympathetic nerve activity was sensitized
      significantly. We conclude that in spontaneously hypertensive rats, increase of
      central "ouabain" by high sodium intake prevents an increase in the sensitivity
      of arterial baroreflex control of renal sympathetic nerve activity, as observed
      in Wistar-Kyoto rats on high sodium diets.

PMID- 7721437
TI  - Antihypertensive actions of the novel nonpeptide endothelin receptor antagonist
      SB 209670.
AB  - Indirect evidence has implicated endothelin-1 in the pathogenesis of
      hypertension. In the present study we examined such a role directly with SB
      209670, a novel nonpeptide endothelin receptor antagonist. The antihypertensive
      and hemodynamic effects of SB 209670 were examined in conscious, unrestrained
      spontaneously hypertensive (SHR), normotensive Wistar-Kyoto (WKY), and renin
      hypertensive rats. Sustained intravenous infusion of SB 209670 (10 micrograms.kg
      1.min-1 for 6 hours) produced a significant, reversible reduction in mean
      arterial pressure in SHR but not in WKY rats. The antihypertensive response to 10
      micrograms.kg-1.min-1 SB 209670 (approximately 25 mm Hg reduction in blood
      pressure) was associated with bradycardia (16% decrease in heart rate) but only a
      minimal reduction (3%) in cardiac output, because stroke volume was evaluated (by
      15%). Therefore, the antihypertensive effect of SB 209670 resulted from a
      decrease (13%) in total peripheral resistance. A sustained antihypertensive
      effect could also be observed after intraduodenal administration of SB 209670 (3
      mg/kg) in conscious SHR (reduction of approximately 35 mm Hg 5 hours after
      administration). SB 209670 (3 mg/kg intravenous bolus) did not alter the pressor
      response or tachycardia observed in pithed SHR after stimulation of thoracolumbar
      sympathetic outflow. SB 209670 was also antihypertensive in renin-hypertensive
      rats, lowering blood pressure to an extent similar to that observed in SHR. Thus,
      the data presented provide evidence to support a role for endothelin-1 in the
      pathophysiology of two animal models of hypertension.

PMID- 7721438
TI  - Effects of kinin blockade on the blood pressure of salt-loaded pregnant rats.
AB  - We evaluated whether chronic inhibition of bradykinin B2 receptors by the long
      acting antagonist D-Arg, [Hyp3, Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140) affects
      blood pressure of salt-loaded pregnant rats. Pairs of rats fed a high sodium diet
      (0.84 mmol sodium per gram chow) were mated at 14 weeks of age. Infusion of
      vehicle or Hoe 140 (300 nmol/d per kilogram body weight) was performed throughout
      each dam's pregnancy by use of an Alzet osmotic pump implanted in the abdominal
      cavity. In both groups, no significant change in systolic pressure (tail-cuff
      plethysmography) or renal blood flow (Doppler flow-meter) was observed from that
      in the unmated state to that at midterm pregnancy. In the control group, systolic
      pressure decreased at the 21st day of pregnancy (from 126 +/- 2 to 97 +/- 2 mm
      Hg, P < .01), and renal blood flow increased (from 6.1 +/- 0.1 to 7.5 +/- 0.2
      kHz, P < .01). These changes were nullified by the administration of Hoe 140
      (systolic pressure changing from 124 +/- 2 to 118 +/- 4 mm Hg, P = NS; renal
      blood flow changing from 6.3 +/- 0.2 to 6.2 +/- 0.1 kHz, P = NS). In the group
      given Hoe 140, placental weight was greater (0.50 +/- 0.01 versus 0.43 +/- 0.01 g
      in controls, P < .01) and the fetal/placental weight ratio was reduced (4.53 +/-
      0.09 versus 5.31 +/- 0.17 in controls, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721439
TI  - Acute hypertension increases norepinephrine release in the anterior hypothalamic
      area.
AB  - Neurons in the anterior hypothalamic area play an important role in NaCl
      sensitive hypertension in spontaneously hypertensive rats, and previous studies
      have suggested that baroreceptor feedback modifies the activity of these neurons.
      To test the hypothesis that the release of norepinephrine in the anterior
      hypothalamic area is modified by arterial baroreceptor reflex feedback and that
      this reflex release is disturbed in spontaneously hypertensive rats on a high
      NaCl diet, we used the push-pull technique to measure the release of the
      norepinephrine metabolite 3-methoxy-4-hydroxy-phenylglycol in the anterior
      hypothalamic area. Seven-week-old male spontaneously hypertensive and
      normotensive Wistar-Kyoto rats were placed on a high (8%) or a basal (1%) NaCl
      diet for 2 weeks. The high NaCl diet elevated mean arterial pressure and greatly
      reduced basal norepinephrine metabolite levels in the anterior hypothalamic area
      of the spontaneously hypertensive (but not the control) rats (305 +/- 32 pg/10
      min in the rats consuming 1% NaCl and 93 +/- 9 pg/10 min in the rats consuming 8%
      NaCl). An infusion of tramazoline (an imidizoline that causes long-lasting
      hypertension) that increased arterial pressure by 25 mm Hg elevated anterior
      hypothalamic area norepinephrine metabolite concentrations significantly more in
      the spontaneously hypertensive rats on the 1% NaCl diet (to 392 +/- 46 pg/10 min)
      than in those on the 8% NaCl diet (to 113 +/- 18 pg/10 min). In contrast, in
      Wistar-Kyoto rats the tramazoline-induced increase in arterial pressure elevated
      anterior hypothalamic area norepinephrine metabolite concentrations slightly more
      in rats on the 8% NaCl diet than in those on the 1% NaCl diet.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7721440
TI  - Renal sympathetic nerve activity is increased in obese Zucker rats.
AB  - A low level of sympathetic nerve activity (SNA) to brown adipose tissue has been
      found in genetically obese Zucker rats and may promote obesity through decreased
      thermogenesis. In contrast, acquired obesity is reportedly associated with
      increased SNA. To determine whether low SNA levels in obese Zucker rats extend to
      the kidney, we compared baseline levels of renal SNA in obese and lean conscious
      unrestrained Zucker rats fed for 2 weeks on low salt (0.4% NaCl) and high salt
      (8.0% NaCl) diets. Baseline renal SNA was calculated from multifiber recordings
      obtained before death under conscious, resting conditions and after death. Body
      weight averaged 490 +/- 12 g (mean +/- SEM) in obese rats (n = 17) and 339 +/- 7
      g in lean rats (n = 19). Mean arterial pressure did not differ in obese and lean
      Zucker rats fed the low salt diet. However, on the high salt diet, mean arterial
      pressure was significantly higher in obese rats (n = 8) than in lean rats (n = 9)
      (113 +/- 3 and 101 +/- 3 mm Hg, respectively; P < .05). Baseline renal SNA was
      approximately 2 to 2.5 times higher (P < .05) in obese rats than in lean rats in
      all groups. These studies suggest that obese Zucker rats have heightened levels
      of SNA to the kidney in contrast to reduced SNA to brown adipose tissue.

PMID- 7721441
TI  - Oscillatory potentials of the electroretinogram in hypertensive patients.
AB  - Because alteration of oscillatory potentials of the electroretinogram has been
      described in diabetic patients without signs of diabetic retinopathy as an early
      marker of changes in microcirculation, we studied the behavior of these
      potentials in patients with early-onset hypertension. Electroretinograms were
      recorded in 24 subjects with essential hypertension (blood pressure > 140/90 mm
      Hg) and in 9 age-matched normotensive control subjects (blood pressure < 140/90
      mm Hg). Diabetes and ocular diseases were considered exclusion criteria. Sitting
      blood pressure was measured by a single investigator with a mercury
      sphygmomanometer after each subject had been at rest for 10 minutes. Funduscopic
      changes in all subjects did not exceed stage I World Health Organization
      classification. The oscillatory index was calculated by adding waves O1, O2, and
      O3 within the b wave of the electroretinogram. Statistical analysis was performed
      with Student's t test for paired and unpaired data and linear regression. The
      oscillatory index was significantly reduced in hypertensive patients compared
      with normotensive subjects. An inverse relationship was observed when systolic
      and diastolic blood pressures were plotted against the oscillatory index. In
      conclusion, our data demonstrate that the electrical activity of the retina is
      altered early in the course of hypertension and that the influence of systolic
      pressure on the oscillatory index is greater than that of diastolic pressure.

PMID- 7721442
TI  - Endothelin-1 and its receptors A and B in human aldosterone-producing adenomas.
AB  - Endothelin-1 stimulates aldosterone secretion by interacting with specific
      receptors. Accordingly, we wished to investigate endothelin-1, endothelin-A (ETA)
      receptor, and endothelin-B (ETB) receptor gene expression, localization, and
      properties in aldosterone-producing adenomas and in the normal human adrenal
      cortex. We carried out 125I-endothelin-1 displacement studies with cold
      endothelin-1, endothelin-3, the specific ETA antagonist BQ-123, and the specific
      ETB weak agonist sarafotoxin 6 C and coanalyzed data with the nonlinear iterative
      curve-fitting program LIGAND. We also studied gene expression with reverse
      transcription-polymerase chain reaction with specific primers for endothelin-1,
      ETA, and ETB complementary DNA. Normal adrenal cortices from consenting kidney
      cancer patients (n = 2) and aldosterone-producing adenomas (n = 4) were studied;
      for the latter, surrounding normal cortex and kidney biopsy tissue served as
      controls. To further localize the receptor subtypes, tissue sections were studied
      by autoradiography in the presence and absence of 500 nmol/L BQ-123, 100 nmol/L
      sarafotoxin 6 C, and 1 mumol/L cold endothelin-1. In all tissues examined,
      endothelin-1, ETA, and ETB messenger RNAs were easily detected. However, in
      aldosterone-producing adenomas, both receptors' genes were expressed at a higher
      level than in the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721443
TI  - Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women
      substituted with 17 beta-estradiol and norethisterone acetate. A two-year follow
      up study.
AB  - Postmenopausal women (PMW) have an increased risk of cardiovascular disease that
      is attenuated by hormone replacement therapy (HRT). Inasmuch as hypertension and
      atherosclerosis are associated with diminished endothelium-derived nitric oxide
      (NO), we investigated whether HRT augments NO release in PMW. We determined serum
      levels of nitrite/nitrate (NO2 + NO3) at baseline and during the 6th, 12th, and
      24th months of the study in two groups of PMW. One group (HRT-PMW, n = 13)
      received continuous transdermal administration of 17 beta-estradiol (Estraderm
      TTS-50) supplemented with oral norethisterone acetate (NETA) on days 1 through 12
      of each month, and the other group (control PMW, n = 13) did not receive HRT.
      Blood samples in the HRT-PMW group were collected without regard to whether
      subjects were taking NETA at the time of blood sampling. Serum NO2 + NO3 levels
      increased in HRT-PMW for the duration of the study, whereas serum NO2 + NO3
      levels remained unchanged in control PMW. When all samples regardless of timing
      of collection with respect to NETA treatment were included in the statistical
      analysis, the change in NO2 + NO3 levels in HRT-PMW was significantly greater
      compared with the change in control PMW (P = .037). Likewise, when only those
      samples collected when estradiol-treated subjects were not taking oral NETA were
      included in the statistical analysis, the change in NO2 + NO3 levels in the HRT
      PMW group remained significant (P = .047) compared with control PMW.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7721444
TI  - Identification of arachidonate P-450 metabolites in human platelet phospholipids.
AB  - Phospholipase A2 (Naja mocambique) catalyzed release of epoxyeicosatrienoic acids
      (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) from phospholipids of
      isolated human platelets. The amount of EETs released by phospholipase A2
      measured by gas chromatography/mass spectrometry (GC/MS) was 4.3 +/- 0.9
      pmol/10(6) platelets. No EETs were detected when phospholipase A2 was omitted
      from the incubations. The relative abundance of EET isomers (14,15-EET, 11,12
      EET, 8,9-EET, and 5,6-EET) from human platelets was 5.4:4.5:3.7:1, respectively,
      as established by a new method based on particle-beam liquid chromatography/mass
      spectrometry (LC/MS). Fractionation of platelet phospholipids by normal-phase
      high-performance liquid chromatography followed by hydrolysis and GC/MS analyses
      indicated that the amount of EETs was highest in fractions containing
      phosphatidylinositol and phosphatidylserine (142 and 61 pmol/nmol of phosphorus,
      respectively) while low in phosphatidylcholine and phosphatidylethanolamine (19
      and 11 pmol/nmol of phosphorus, respectively). The majority of EETs associated
      with phosphatidylcholine was found in fractions containing 1-O
      alkylphosphatidylcholine. Human platelet phospholipids also released 20-HETE on
      phospholipase treatment (9.7 +/- 1.6 fmol/10(5) cells) and at least three other
      HETEs, one of which was tentatively identified as 16-HETE. Activation of human
      platelets by thrombin or platelet-activating factor released 5 to 7 fmol
      EET/10(6) cells. Receptor-mediated hydrolysis of phospholipids containing EETs
      and 20-HETE may play a role in stimulus-response coupling in platelets.

PMID- 7721445
TI  - Effect of renal perfusion pressure on renal interstitial hydrostatic pressure and
      sodium excretion. Role of vasopressin V1 and V2 receptors.
AB  - Renal interstitial hydrostatic pressure (RIHP) has recently been cited as an
      important mediator of pressure natriuresis. Our objective was to determine the
      roles of vasopressin V1 and V2 receptors in mediating the effects of renal
      perfusion pressure (RPP) on RIHP and sodium excretion (UNaV). The effects of RPP
      on renal hemodynamics, RIHP, and UNaV were assessed in control Wistar rats (n =
      10) and in rats pretreated with intravenous infusion of the specific nonpeptide
      vasopressin V1 antagonist OPC-21268 (100 micrograms.kg-1.min-1; n = 8) and the V2
      antagonist OPC-31260 (40 micrograms.kg-1.min-1; n = 10). Increasing RPP from 95
      to 118 mm Hg in control rats increased RIHP (6.4 +/- 1.0 to 9.9 +/- 1.3 mm Hg),
      UNaV (0.29 +/- 0.03 to 0.52 +/- 0.05 muEq.min-1.g-1), urine flow rate (UFR) (5.2
      +/- 0.3 to 7.6 +/- 0.6 microL.min-1.g-1), and the fractional excretion of sodium
      (FENa). In rats pretreated with V1 antagonist, similar results were obtained for
      urine osmolality and the responses of RIHP, UNaV, UFR, and FENa to RPP. V2
      antagonist reduced urine osmolality (392 +/- 47 compared with 979 +/- 88 mOsm.kg
      1 in control rats) and enhanced the responses of UNaV (0.43 +/- 0.08 to 1.32 +/-
      0.32 microEq.min-1), UFR (17.8 +/- 3.2 to 29.2 +/- 3.8 microL.min-1.g-1), and
      FENa to RPP, but the RIHP response resembled that observed in the control and V1
      antagonist groups. Renal blood flow and glomerular filtration rate did not differ
      among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721446
TI  - Differential regulation of angiotensin II receptor subtypes in rat kidney by low
      dietary sodium.
AB  - This study was designed to determine whether expression of renal messenger RNA
      (mRNA) encoding the two known angiotensin II type 1 (AT1) receptor subtypes (AT1A
      and AT1B) can be regulated by dietary sodium. Seven-week-old male Wistar rats
      were fed a low-sodium diet (0.07%, n = 9) or a normal-sodium diet (0.5%, n = 9
      [control]) for 14 days. A rat AT1 complementary DNA (cDNA) probe, which
      hybridizes to mRNA encoding both the AT1A and AT1B receptor subtypes, and cDNA
      probes, which are selective for AT1A or AT1B mRNA, were used in Northern blot or
      in situ hybridization analysis. By use of Northern blot analysis, renal mRNA
      levels for the AT1 and AT1A receptors in rats fed a low-sodium diet were found to
      be increased twofold (P < .05) compared with control. Because renal AT1B mRNA
      content was not detected by Northern blot analysis, quantitative image analysis
      of in situ hybridization with a digoxigenin-labeled cRNA probe made from AT1B
      cDNA was used. In situ hybridization analysis indicated that AT1B mRNA was
      expressed in the proximal and collecting tubules of the kidney in rats fed a
      normal-sodium diet. The low-sodium diet significantly decreased the percent
      positive staining area of AT1B mRNA in the renal cortex (5.51 +/- 0.77% versus
      2.73 +/- 0.35%, P < .05) and medulla (4.76 +/- 0.70% versus 2.01 +/- 0.43%, P <
      .05) compared with the control diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721447
TI  - Renal afferent denervation prevents hypertension in rats with chronic renal
      failure.
AB  - Increased activity of the sympathetic nervous system has been described in
      chronic renal failure, but its role in the genesis and maintenance of
      hypertension associated with this condition has not been established. The kidney
      has an intense network of chemoreceptors and baroreceptors that send impulses to
      the brain. To what extent activation of these receptors by the scarred kidney or
      the uremic milieu may contribute to this model of hypertension is unknown. In the
      present study, we evaluated the effect of bilateral dorsal rhizotomy on the
      development of hypertension and neuroadrenergic activity in the anterior,
      lateral, and posterior hypothalamic nuclei, in the locus ceruleus, and in the
      nucleus tractus solitarius of Sprague-Dawley rats that underwent 5/6 nephrectomy
      or were sham operated. Neuroadrenergic activity was determined by calculating
      norepinephrine turnover rate after inhibition of norepinephrine synthesis with
      alpha-methyl-DL-p-tyrosine methyl ester hydrochloride. The endogenous
      norepinephrine concentration was significantly greater in the posterior and
      lateral hypothalamic nuclei and the locus ceruleus, but not in the nucleus
      tractus solitarius, and the anterior hypothalamic nuclei of uremic rats compared
      with control rats. In rats with chronic renal failure and sham rhizotomy, the
      turnover rate of norepinephrine in the posterior (15.3 +/- 1.61 nmol.g-1.h-1) and
      lateral hypothalamic nuclei (11.7 +/- 2.12 nmol.g-1.h-1) and in the locus
      ceruleus (26.6 +/- 2.42 nmol.g-1.h-1) was significantly faster (P < .01) than in
      rats with renal failure and dorsal rhizotomy (4.1 +/- 0.51, 4.7 +/- 0.77, and 5.1
      +/- 1.13 nmol.g-1.h-1, respectively) or control animals with or without
      rhizotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721448
TI  - Endothelin antagonists improve renal function in spontaneously hypertensive rats.
AB  - Hypertension in the spontaneously hypertensive rat (SHR) is associated with
      reduced renal excretory function, low renal plasma flow, reduced glomerular
      filtration rate, and reduced renal interstitial hydrostatic pressure. The
      mechanisms responsible for these abnormalities in renal function are unknown. The
      purpose of this study was to determine the role of intrarenal endothelin in
      altering renal hemodynamic and excretory function in the SHR. Both PD 145065 (an
      endothelin A and B receptor antagonist) and FR 139317 (a selective endothelin A
      receptor antagonist) or saline was infused into the renal interstitium of 14- to
      16-week-old SHR (n = 7) and age-matched Wistar-Kyoto rats (WKY) (n = 7). Renal
      perfusion pressure in some SHR was reduced to that of the WKY by a servocontrol
      system. At a renal perfusion pressure of 124 +/- 4 mm Hg, infusion of PD 145065.
      (0.03 mg.kg-1.min-1) and FR 139317 (0.02 mg.kg-1.min-1) significantly increased
      glomerular filtration rate (delta 22%), renal plasma flow (delta 37%), and renal
      interstitial hydrostatic pressure (from 3.2 +/- 0.5 to 5.4 +/- 0.6 mm Hg) in the
      SHR. These changes were associated with significant increases in urine flow,
      absolute sodium excretion, and fractional excretion of sodium. Similar
      improvements in renal plasma flow, renal interstitial hydrostatic pressure, and
      renal excretory function were obtained in the SHR whose renal perfusion pressure
      was not reduced (n = 7). Renal interstitial infusion of endothelin receptor
      antagonists had no effect on renal hemodynamic or excretory function in the WKY.
      These data demonstrate that endothelin receptor blockade within the kidney
      improves renal hemodynamic and excretory function in the SHR.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7721449
TI  - Increased hyaluronic acid in the inner renal medulla of obese dogs.
AB  - Dogs placed on a high-fat diet develop obesity and hypertension associated with
      marked sodium retention that is due to increased tubular reabsorption. Previous
      studies showed that renal interstitial hydrostatic pressure is elevated in obese
      dogs compared with lean dogs, and histological studies revealed increases in
      medullary interstitial cells and expansion of the medullary but not the cortical
      extracellular matrix. This matrix stained intensively with Alcian Blue at pH 2.6,
      colloidal iron, and periodic acid-Schiff, suggesting increased
      glycosaminoglycans. The goal of this study was to quantitate medullary
      glycosaminoglycan content in obese (n = 8) compared with lean (n = 8) dogs.
      Measurement of total glycosaminoglycan content, estimated from uronic acid
      content, and of hyaluronate, the most abundant glycosaminoglycan in canine renal
      medulla, with an enzyme-linked immunosorbent assay indicated that there were no
      significant differences in total glycosaminoglycan or hyaluronate contents in the
      outer medulla of obese dogs compared with those in lean dogs. In contrast, in the
      inner medulla of obese dogs there was a 140% increase in hyaluronate compared
      with the content in lean dogs (4.3 +/- 0.5 versus 1.8 +/- 0.2 mg hyaluronate per
      gram wet tissue, respectively; P < .05); however, total glycosaminoglycan content
      was not significantly different (6.9 +/- 0.7 versus 6.2 +/- 0.5 mg uronic acid
      per gram wet tissue) in obese and lean dogs. These results suggest a change in
      the relative proportion of the glycosaminoglycan species in the inner medulla of
      obese dogs, with a selective increase in hyaluronate.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7721450
TI  - Renal denervation attenuates the sodium retention and hypertension associated
      with obesity.
AB  - Recent studies have indicated that obesity is associated with hypertension,
      sodium retention, and increased sympathetic nervous system activity. The purpose
      of this study was to determine the role of renal nerves in mediating the sodium
      retention and hypertension associated with obesity. We determined the hemodynamic
      and renal excretory responses to a high-fat diet in control (n = 6) and
      bilaterally renal-denervated (n = 7) chronically instrumented dogs. After a
      control period of 8 days, dogs were placed on a high-fat diet for 5 weeks. In
      response to a high-fat diet, body weight increased from 19.9 +/- 2.2 to 29.9 +/-
      2.4 kg in the control group and from 21.1 +/- 2.0 to 32.4 +/- 1.9 kg in the
      bilaterally renal-denervated group. Heart rate increased from 81 +/- 8 to 113 +/-
      7 beats per minute in the control group and from 79 +/- 7 to 103 +/- 8 beats per
      minute in the bilaterally renal-denervated group. Arterial pressure increased
      significantly from 95 +/- 2 to 109 +/- 4 mm Hg in the control group. In contrast,
      5 weeks of a high-fat diet in the bilaterally renal-denervated group did not
      significantly increase arterial pressure (which went from 87 +/- 3 to 90 +/- 4 mm
      Hg). Furthermore, the decrease in sodium excretion in response to the high-fat
      diet was significantly greater in the control group than in the bilaterally renal
      denervated group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721451
TI  - Effects of L-arginine infusion on renal hemodynamics in patients with mild
      essential hypertension.
AB  - Previous studies have shown that endothelium-derived relaxing factor/nitric oxide
      plays an important role in the regulation of systemic and renal hemodynamics. The
      purpose of the present study was to determine whether endothelium-dependent
      renovascular relaxation was impaired in patients with mild essential hypertension
      who had normal renal plasma flow and glomerular filtration rate. We evaluated the
      effects of intravenous administration of L-arginine on blood pressure and renal
      hemodynamics in 13 patients with mild essential hypertension and 15 normotensive
      control subjects. L-Arginine infusion (500 mg/kg over 30 minutes) reduced mean
      blood pressure (from 82.5 +/- 2.5 to 76.3 +/- 2.6 mm Hg in hypertensive patients
      and from 106.1 +/- 3.0 to 97.5 +/- 2.9 mm Hg in control subjects; P < .001) and
      renovascular resistance (from 0.084 +/- 0.009 to 0.067 +/- 0.009 mm Hg.mL-1.min
      1.[1.48 m2]-1 and from 0.105 +/- 0.010 to 0.093 +/- 0.011 mm Hg.mL-1.min-1.[1.48
      m2]-1, respectively; P < .001). L-Arginine infusion increased renal plasma flow
      (from 602 +/- 36 to 698 +/- 40 mL.min-1.[1.48 m2]-1, P < .05) in normotensive
      subjects but not in hypertensive subjects, and glomerular filtration rate was
      unaffected in both groups. Although the L-arginine-induced reduction in mean
      blood pressure was similar in both groups, the decline in renovascular resistance
      was smaller in hypertensive subjects. The response of renal plasma flow was also
      smaller in hypertensive subjects. These findings suggest that dysfunction of the
      L-arginine-nitric oxide pathway exists in the renal circulation even in mild
      essential hypertension with normal renal plasma flow and glomerular filtration
      rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721452
TI  - CIBA Award for Hypertension Research. 1994.

PMID- 7721453
TI  - CIBA Award for Hypertension Research. 1994.

PMID- 7721454
TI  - Council for High Blood Pressure Research Lifetime Achievement Award. 1994.

PMID- 7721455
TI  - 11th annual Marion Merrell Dow Hypertension Research Clinical Fellowship Award.
      1994.

PMID- 7721456
TI  - Harry Goldblatt Award in Cardiovascular Research. 1994.

PMID- 7721457
TI  - Arthur C. Corcoran Memorial Lecture. 1994.

PMID- 7721458
TI  - F. Merlin Bumpus Memorial Lecture. 1994.

PMID- 7721459
TI  - Merck Young Investigator Award. 1994.

PMID- 7721460
TI  - Released PMN elastase: an indicator of postsurgical uneventful wound healing and
      early inflammatory complications. A contribution to the search for objective
      criteria in wound healing monitoring.
AB  - Monitoring of postoperative wound healing is important for the early diagnosis of
      postoperative infective complications in order to decrease morbidity. The purpose
      of this study was to search for a discriminatory time point between uneventful
      wound healing and early wound infections after operations for orthopaedic trauma
      using PMN elastase. This proteolytic enzyme is a biochemical marker for
      pathological granulocyte stimulation. The two groups of injured patients
      comprised persons with 'per priman' (pp) wound healing without complications-
      group 1 (N = 31)--and the early manifestation of a bacterial wound infection 'per
      secundam' (ps) during the healing phase--group 2 (N = 4). In group 1, surgical
      trauma was accompanied by an increase in PMN elastase levels reaching the maximum
      within the first 3 postoperative days; values returned to normal on day 10. In
      group 2 PMN elastase median levels showed recurring increases throughout. No
      normal values were observed. There was a highly significant difference (P < 0.01)
      on days 4 and 5 in group 2 compared with the control group 1. Since PMN elastase
      can be determined on an autoanalyser, and the enzyme is of proven discriminatory
      value, it is suggested that this marker should become part of the daily
      diagnostic routine in the care of the injured.

PMID- 7721461
TI  - Results of extensor tendon repair performed by junior accident and emergency
      staff.
AB  - The results of 46 extensor tendon repairs performed by junior accident and
      emergency doctors were assessed, with a minimum follow up of 6 months. Based on
      Miller's assessment, 80 per cent of the proximal injuries achieved excellent or
      good results. Only 18 per cent of distal injuries achieved excellent or good
      results. Neither grip or fingertip pinch strength were significantly reduced.
      Sixty-seven per cent of patients complained of no residual pain and only 7 per
      cent complained of the injured digit getting in the way.

PMID- 7721462
TI  - Open reduction and internal fixation for displaced intra-articular fractures of
      the os calcis.
AB  - Thirty-one patients with displaced intra-articular fracture of the os calcis who
      were admitted to Queen Mary Hospital, Hong Kong from 1989 to 1991 and who
      underwent open reduction and internal fixation and bone grafting of the os
      calcis, were followed up for at least 30 months. Pre- and postoperative X-rays
      were taken. Functional results were assessed clinically in terms of pain,
      deformities, activities and motion loss. The majority of the patients had
      acceptable functional outcome. The results were analysed in an attempt to
      correlate with the fracture pattern.

PMID- 7721463
TI  - Dynamization timing and its effect on bone healing when using the Orthofix
      Dynamic Axial Fixator.
AB  - We report the effect of dynamization timing on healing rates when treating tibial
      fractures with the Dynamic Axial Factor (Orthofix, registered trademark). Sixty
      nine patients with 71 fresh tibial fractures were grouped retrospectively for
      age, Gustilo and Anderson wound grading, site of tibial fracture and presence of
      an intact fibula or stable fibular fracture. Pairs were then generated
      chronologically to compare healing rates in those patients dynamized before 4
      weeks with those dynamized after this time. This resulted in 22 pairs of
      patients; the other fractures could not be paired. Their healing times were
      compared using a paired t-test and were found to be significantly quicker in the
      group dynamized within the first 4 weeks (P < 0.05) and we therefore recommend
      that this should be routine practice.

PMID- 7721464
TI  - A black eye with a twist.

PMID- 7721465
TI  - Complex dislocation of the metacarpophalangeal joint of the index finger with
      sesamoid entrapment.

PMID- 7721466
TI  - Unusual avulsions of the patella tendon in two schoolboy athletes; case reports
      and discussion with reference to the literature.

PMID- 7721467
TI  - Fracture dislocation with associated humeral shaft fracture.

PMID- 7721468
TI  - High-velocity gunshot wound through bone with low energy transfer.

PMID- 7721469
TI  - Modification to Red Cross wound classification.

PMID- 7721470
TI  - Safe manipulation of penile zip entrapment.

PMID- 7721471
TI  - Effects of method of internal fixation of symphyseal disruptions on stability of
      the pelvic ring.
AB  - This study tested different methods of internal fixation of a symphyseal
      disruption, in comparison with the mechanics of the intact pelvis. Unembalmed
      cadaveric pelves were tested in simulated bilateral stance in a servohydraulic
      materials-testing machine. Motion of the superior and inferior pubic symphysis,
      and at two levels of the posterior sacroiliac complex, was measured using high
      resolution displacement transducers. The fixations tested were (1) double plating
      (4.5 mm reconstruction plates), (2) wire loops around two 6.5 mm, fully threaded
      cancellous screws, and (3) an absorbable suture material (polydioxanone). Each
      pelvis was first tested intact, recording displacements in response to a cyclic
      axial load up to a maximum of 500 N applied through the proximal sacrum. The
      pubic symphysis was then sectioned and the sacrum fractured to produce an
      unstable pelvis (Tile C-type). Recordings were then repeated, following fixation
      of the sacral fracture with lag screws and sequential fixation of the symphysis
      with each of the test methods. The results from eight pelves revealed that
      internally fixed symphyseal motion was generally greater than intact, regardless
      of fixation method. The superior symphysis was usually compressed, while there
      was distraction inferiorly. Wiring resulted in significantly less symphyseal
      motion than the other methods (P < 0.02), provided four loops were used, reducing
      the separation inferiorly. There was no significant difference in sacral fracture
      motion between the three methods. The results indicate that in osteoporotic bone,
      as used in this study, symphyseal wiring is best able to oppose the tensile loads
      in the inferior symphysis that are associated with bilateral stance loading.
      These biomechanical findings must be interpreted within the broader context of
      surgical management of these complex injuries.

PMID- 7721472
TI  - Unstable pelvic fractures: a retrospective analysis.
AB  - Thirty-nine patients with unstable pelvic fractures were analysed
      retrospectively. The mean age of the group was 41 years (range 15-77). Of these
      cases 35 had sustained high energy trauma. The mean Hospital Trauma Index-Injury
      Severity Score of the population was 32 (16-66). Nine cases were haemodynamically
      unstable on admission. The type of unstable pelvic fracture was classified
      according to Tile. Sixteen patients had a type B fracture and 23 had a vertical
      instability (type C) fracture. In two patients, an open fracture was seen.
      Directly associated injuries were diagnosed in 11 patients, of which eight showed
      damage of the urogenital system, three of the rectum and three of the peripheral
      nerve system. In seven cases the fracture was treated non-operatively; in the
      remaining 32 patients the pelvic ring was stabilized operatively. Additional
      therapy for hypovolaemic shock due to pelvic bleeding was necessary in six cases.
      The overall mortality in this series was 13 per cent. Early and aggressive
      resuscitation and standardized treatment in well-equipped and staffed injury
      centres is mandatory in these severely traumatized patients to achieve optimal
      results and to minimize the risk of fatal outcome.

PMID- 7721473
TI  - Paediatric injuries on an artificial ski slope.
AB  - Skiing on artificial ski slopes is enjoyed by a large number of children, but the
      rate and types of injuries amongst young skiers is unknown. During a 1 year
      prospective study the rate of injury was one per 394 h skied. One hundred and
      twelve children sustained 116 injuries, including 52 fractures. The ratio of
      upper to lower limb injuries was 4.5 to 1, with the thumb being the most commonly
      injured site. Although most injuries resulted from simple falls, five of the 12
      patients with the most severe injuries (requiring admission), had injured
      themselves by crashing into the barrier at the bottom. It is concluded that the
      rate of injury to children on this artificial ski slope is unacceptably high.
      Measures are suggested to improve safety for children. These include: increasing
      supervision, carefully controlling numbers, enforcing the use of thumbless
      mittens with restrictions on the use of ski poles, increasing the 'run-off' area
      and improving padding on the barriers at the bottom. The different requirements
      of children from adults deserve consideration when introducing them to what were
      once 'adult' sports.

PMID- 7721474
TI  - Urinary tract infection and hip fracture.
AB  - A routine audit revealed that in 25 per cent of patients with proximal femoral
      fracture, hospital stay was complicated by urinary tract infection (UTI). A
      prospective study was undertaken to investigate the relationship of UTI to
      fracture type, timing of surgery and the effect of perioperative antibiotics.
      Eighty-eight patients were investigated over a 4-month period with urine
      specimens obtained at time of operation and 48 h from operation. Of the patients,
      all female, 12.5 per cent had positive urine cultures at the time of operation.
      Of all patients, 42 per cent had positive urine cultures 48 h after operation.
      Females with intra-capsular fractures were more likely to have positive cultures
      both pre- and post-operatively (P < 0.005). Age (P < 0.05) and operative delay
      beyond 48 h (P < 0.05) were also found to predispose to infection. All patients
      except one who had urinary infection at the time of surgery had post-operative
      urine infection with the same organism. Present audit methods have significantly
      under estimated the presence of UTI in these patients. Fracture type and
      operative delay would appear to be the most significant determinants of a
      positive urine culture 48 h after operation. Prophylactic antibiotics appear to
      be ineffective in eradicating pre-existing or preventing early post-operative
      infection.

PMID- 7721475
TI  - The management of gunshot fractures of the humerus.
AB  - We report 37 patients who were treated for gunshot fractures of the humerus
      during a 6 month period at the ICRC hospital, Lopiding, on the Sudanese border.
      Initial treatment followed the established principals for war surgery. The
      strategy for fracture stabilization however remains controversial. External
      fixation has been widely used in war surgery. This paper compares the different
      methods of stabilization for humeral fractures available in a field hospital.
      Fracture healing was delayed after external fixation and infection persisted
      longer than with the other methods of immobilization such as skeletal traction,
      functional bracing and 'collar and cuff' support. In the author's experience,
      external fixation has no advantage over non-operative methods for comminuted
      gunshot fractures of the humerus, unlike its use on the lower limb. The best
      results for fracture healing and final function were achieved by functional
      bracing.

PMID- 7721476
TI  - The disability status of injured patients measured by the functional independence
      measure (FIM) and their use of rehabilitation services.
AB  - The type and severity of disability following major trauma was evaluated using
      the Functional Independence Measurement (FIM) in 93 patients brought to the Royal
      London Hospital (RLH) by helicopter. The range of values for FIM is from 18
      (dependent) to 126 (fully independent) in the six sections of self-care,
      sphincter control, mobility, locomotion, communication and social cognition. The
      sections are divided into 18 separate items and graded 1-7. Forty-eight patients
      were discharged directly to home with a median FIM score of 124; 11 were
      transferred to another acute hospital with a median FIM of 63 and seven went to
      rehabilitation unit with a median FIM of 58. At six months, 79 per cent of the
      patients reported no disability and 89 per cent of the original 93 patients were
      at home with a median FIM of 126. The mean amount of rehabilitation provided at
      the RLH for all patients was 11 h 20 min with a mean in-patient length of stay of
      14 days. The actual and optimal amount of therapy for rehabilitation worked out
      at less than 1 h per day in the acute hospital. FIM is a useful, practical and
      simple methodology for recording disability in the acute hospital. It provides a
      measure for assessing the original disability, its progress and residual
      limitations. Nurses, doctors and therapists can use it for establishing care
      plans and goals as well as deciding the transfer of the patient to the most
      appropriate place for future care.

PMID- 7721477
TI  - Magnesium deficiency prolongs myocardial stunning in an open-chest swine model.
AB  - The effect of magnesium deficiency on postischemic myocardial dysfunction
      (myocardial stunning) in an open-chest swine model was studied. Twelve swine were
      assigned either to low magnesium diet or control diet. Myocardial stunning was
      assessed by measuring regional wall thickening by epicardial Doppler before and
      after brief occlusion (8 min) of the left anterior descending coronary artery.
      Serum magnesium levels decreased significantly in the experimental group only.
      Glutathione levels were 42.6% lower in the magnesium deficient swine than in
      controls. Stunning time was significantly prolonged from 32.8 +/- 3.1 min in the
      control group to 43.8 +/- 4.6 min in the hypomagnesemic swine. In conclusion,
      magnesium deficiency is associated with prolonged recovery from myocardial
      stunning.

PMID- 7721478
TI  - Characterization of aneurysmal transformation in perimembranous ventricular
      septal defects: an adhered anterior leaflet of tricuspid valve predisposes to the
      development of left ventricular-to-right atrial shunt.
AB  - BACKGROUND: The most common type of left ventricular-to-right atrial shunts are
      those associated with perimembranous ventricular septal defect when the defects
      diminish in size via aneurysmal transformation. This study is to characterize the
      echocardiographic features and to determine the possible mechanisms. METHODS AND
      RESULTS: From January 1986 to December 1992, of 930 consecutive patients with
      isolated perimembranous ventricular septal defect, 692 showed evidence of
      aneurysmal transformation. Excluding those with subaortic ridge,
      echocardiographic analysis was based on 664 of them. Of these, 94 patients had
      left ventricular-to-right atrial shunts, 115 had their defects spontaneously
      closed and in 455 only interventricular shunt persisted. Four types of
      echocardiographic findings featured in the aneurysmal transformation process:
      type A, both the anterior and septal leaflets of tricuspid valve contributed to
      the process; type B was similar to type A, but the arc-like structure from the
      anterior leaflet is much less evident; in type C, only the septal leaflet, and in
      type D, other adjacent tissues, contribute to the aneurysmal transformation. Type
      A morphology was closely associated with the development of left ventricular-to
      right atrial shunt while types C and D were most commonly seen in those
      spontaneously closed defects and those with only interventricular shunt. The
      vegetations of infective endocarditis were located at the atrial side of the
      tricuspid valve in patients with left ventricular-to-right atrial shunts, while
      they were in the right ventricle in those with only interventricular shunt.
      CONCLUSION: The morphology of the aneurysmal transformation in perimembranous
      ventricular septal defect can be characterized by echocardiograms. Although the
      septal leaflet of the tricuspid valve is usually involved in this process, it is
      the incorporation of the anterior leaflet that predisposes to the development of
      left ventricular-to-right atrial shunts.

PMID- 7721479
TI  - Unusual coronary artery pattern in a criss-cross heart.
AB  - In a case of criss-cross heart with atrioventricular and ventriculoarterial
      concordance, the right coronary artery and left anterior descending arose from
      the right hand sinus; the left circumflex originated from the left hand sinus.
      This pattern existed because of a persistent circle of Vieussens across the right
      ventricular outflow tract which located superiorly and leftward in such a criss
      cross heart.

PMID- 7721480
TI  - Captopril cardioplegia on myocardial protection in the hypertrophied rat hearts.
AB  - Hearts with pressure-overload hypertrophy show an increased intracardiac
      activation of the renin-angiotensin system (RAS) which may contribute to
      myocardial ischemia and reperfusion injury. This study investigates whether the
      hypertrophied myocardium is more vulnerable to ischemia and reperfusion injury
      and whether the specific inhibition of the cardiac RAS by captopril would modify
      ischemia and reperfusion injury in the hypertrophied myocardium. By using the
      isolated working rat heart model, hypertrophied hearts, induced by abdominal
      aortic banding for 6 weeks, were subjected to 120 min of hypothermic ischemic
      arrest followed by 30 min of reperfusion. The postischemic cardiac function
      recovery was measured in both the untreated (n = 10) and the captopril-treated (n
      = 11) groups and was compared with that of the sham-operated non-hypertrophied
      control hearts (n = 10). Captopril (23.0 microM) was given to one group with the
      hypertrophied hearts from the beginning of ischemia to the end of reperfusion. In
      comparison with the normal control hearts, the cardiac function recovery after 30
      min reperfusion was poorer in the hypertrophied hearts, which was associated with
      a lower recovery of coronary flow (CF), a higher myocardial lactate content and a
      retarded peak myocardial creatinkinase (CK) release. Captopril significantly
      improved the cardiac function recovery, which was associated with an increased CF
      recovery and a lower myocardial lactate content, and a rapid peak CK release. In
      conclusion, this study shows that the hypertrophied myocardium leads to an
      increased susceptibility to ischemia and reperfusion injury. Captopril, most
      likely by its inhibition of the cardiac RAS, is effective in preventing the
      ischemia and reperfusion injury in the hypertrophied heart.

PMID- 7721481
TI  - Relation of left atrial volume and systolic function to the hormonal response in
      idiopathic dilated cardiomyopathy.
AB  - We studied the relation of left atrial mechanical function to the hormonal
      response in 14 patients with idiopathic dilated cardiomyopathy. Left atrial
      volumes were echocardiographically measured at mitral valve opening (maximal), at
      onset of atrial systole (onset of the P wave of the electrocardiogram) and at
      mitral valve closure (minimal) from the apical 2- and 4-chamber views using the
      biplane area-length method. Left atrial systolic function was assessed with the
      left atrial active emptying fraction ([volume at onset of atrial systole
      minimal]/[volume at onset of atrial systole]). Plasma renin activity, aldosterone
      and atrial natriuretic peptide plasma levels were determined using commercially
      available kits. Left atrial maximal volume was directly, and left atrial active
      emptying fraction was inversely related to plasma renin activity (r = 0.60, P =
      0.02 and r = -0.59, P = 0.026, respectively), aldosterone (r = 0.61, P = 0.02 and
      r = -0.53, P = 0.048) and atrial natriuretic factor (r = 0.79, P = 0.0009 and r =
      -0.62, P = 0.01) plasma levels. Thus, increased left atrial size and depressed
      left atrial contractile performance are associated with increased hormonal
      response in idiopathic dilated cardiomyopathy.

PMID- 7721482
TI  - Doppler evaluation of left ventricular diastolic filling in Behcet's disease.
AB  - Although cardiac involvement such as pericarditis, myocarditis, coronary
      arteritis and valvular disease in Behcet's disease occurs, few studies have
      assessed left ventricular diastolic function. This study assesses the prevalence
      of both systolic and diastolic left ventricular dysfunction in patients with
      Behcet's disease who have no clinical cardiac manifestations. Twenty-two patients
      (12 women and 10 men, mean age 34 +/- 2.4 years) underwent full clinical
      examination, electrocardiography, M-mode, two-dimensional, and Doppler
      echocardiography. The mean disease duration was 5 +/- 4.7 years (range, 1 month
      16 years). As age and sex-matched control group of 20 healthy subjects was also
      studied. Prolonged isovolumic relaxation time, prolonged deceleration time,
      reversal of the early and late peak transmitral diastolic flow velocities, late
      peak transmitral diastolic flow velocities (E/A ratio) and increased atrial
      filling fraction were noted in five patients. It is concluded that left
      ventricular dysfunction occurs frequently in patients with Behcet's disease and
      Doppler echocardiography may be valuable in detecting diastolic filling
      abnormalities as an early sign of cardiac involvement.

PMID- 7721483
TI  - Atrial natriuretic peptide: relation to left ventricular filling properties in
      patients with systemic sclerosis.
AB  - To determine the relation between left ventricular filling properties and plasma
      atrial natriuretic peptide in systemic sclerosis, we evaluated 30 consecutive
      patients and 48 age- and sex-matched controls. The venous plasma atrial
      natriuretic peptide was measured by radio-immunoassay. Left ventricular
      involvement was evaluated by echocardiography and mitral regurgitation was
      evaluated by Doppler. The patient group had markedly elevated plasma atrial
      natriuretic peptide as compared to the matched controls, (239.4 +/- 59 vs. 178.2
      +/- 36 pmol/l, P < 0.0005). We found signs of impaired left ventricular filling
      properties among the patients with an increase of the Doppler A-wave velocity and
      A/E ratio. A relative reduction of early filling was found in spite of some
      degree of mitral regurgitation in two-thirds of the patients. The plasma atrial
      natriuretic peptide concentration was related to the A-wave velocity (r = 0.44, P
      < 0.0005), the A/E ratio (r = 0.40, P < 0.005), and also to the degree of mitral
      regurgitation (r = 0.43, P < 0.005). The relationship to the A-wave velocity
      remained when considering possible confounding factors. We conclude that the
      previously observed fibrotic process in systemic sclerosis does not prevent
      production and liberation of plasma atrial natriuretic peptide in relation to
      factors distending the left atrium, such as altered left ventricular filling
      properties and the presence of mitral regurgitation. However, the moderate
      relationships between atrial natriuretic peptide and haemodynamic variables
      indicate that the peptide might also be an independent indicator of cardiac
      involvement in systemic sclerosis.

PMID- 7721484
TI  - Anatomic substrate of the slow atrio-ventricular nodal pathway in an experimental
      atrio-ventricular nodal reentrant tachycardia.
AB  - We investigated the anatomic substrate of the slow pathway of the atrio
      ventricular (AV) node in a dog with AV nodal reentrant tachycardia. Sustained AV
      nodal reentrant tachycardia was repeatedly induced in a mongrel dog after putting
      cryolesions on the anterior atrial septum for 1 month. A posterior perinodal
      dissection was performed for ablation of the slow pathway and cure of the
      tachycardia. After the operation, AV nodal reentrant tachycardia and
      discontinuity of the AV conduction were no longer demonstrated. A histologic
      examination of the AV junction revealed that the dissection injured mainly in two
      areas: (1) the superficial atrial fibers of the subendocardium over the compact
      AV node; and (2) the inferior portion of the posterior atrial inputs near the
      tricuspid annulus. The compact AV node and its transitional cells remained
      intact. In conclusion, our results suggested that (1) the anatomic circuit of AV
      nodal reentrant tachycardia does involve some extranodal atrial tissues; and (2)
      the superficial right atrial fibers over the AV node and/or the inferior portion
      of the posterior atrial inputs, contribute to part of the slow AV nodal pathway.

PMID- 7721485
TI  - Asystolic arrest as a presentation of sarcoidosis.
AB  - A 41-year-old man who presented with a history of sudden loss of consciousness
      suffered two further episodes during which asystole was documented. Subsequent
      investigations included exercise stress testing, thallium scintigraphy,
      electrophysiological studies, CT-scan of chest, Kveim test and a gallium-67 scan,
      which led to a presumptive diagnosis of averted sudden death as a first
      presentation of sarcoidosis with primary cardiac involvement.

PMID- 7721486
TI  - Repeatability of measurements of pulmonary venous flow indices.
AB  - We investigated the measurement repeatability of four pulmonary venous flow
      indices. The indices were measured on 45 anonymised, transthoracic Doppler
      recordings of adequate technical quality. Measurements were taken by two
      independent observers, and repeated after 10 days. Plus/minus the repeatability
      coefficient, which was used to quantify repeatability, gives the 95% probability
      limits for random variation between repeated measurements. The index D-diff,
      which is the difference in duration of the pulmonary venous flow reversal during
      atrial systole and the transmitral A-wave, had repeatability coefficients of 50
      and 57 ms intra- and inter-observer. For the fraction of antegrade pulmonary
      venous flow during ventricular systole, the coefficients were 12 and 13
      percentage points, but improved to 6 and 7 among the high-quality recordings. The
      retrograde pulmonary venous flow during atrial systole as a fraction of the
      antegrade flow, had coefficients of 5 percentage points both intra- and inter
      observer. The coefficient for the peak velocity of retrograde pulmonary venous
      flow was 0.05 m/s intra- and inter-observer. Thus, the systolic fraction was the
      only index that showed a satisfactory repeatability. We suggest that if the other
      indices are used, measurements should be taken by a blinded observer to avoid
      observer bias.

PMID- 7721487
TI  - Ruptured aneurysm of the sinus of Valsalva in a patient with Behcet's disease.
AB  - The vast majority of sinus of Valsalva aneurysm originated from a localized
      congenital defect of the aortic media and less frequently from infections or
      degenerative processes affecting the aortic wall. But aneurysm of sinus of
      Valsalva has not been reported up to the present in a patient with Behcet's
      disease. We report a 39-year-old woman presenting ruptured aneurysm of the sinus
      of Valsalva and Behcet's disease.

PMID- 7721488
TI  - Heroin abuse and myocardial infarction.
AB  - A young woman developed an acute transmural infarction due to an acute thrombosis
      of the left anterior descending coronary artery, probably induced by a previous
      abuse of intravenous heroin.

PMID- 7721489
TI  - Instantaneous resolution of ischemic mitral regurgitation and pulmonary
      hypertension by angioplasty.

PMID- 7721490
TI  - Ventricular septal rupture following blunt chest trauma after a long delay: a
      case report.
AB  - We observed a patient with ventricular septal rupture occurring 33 days after a
      blunt chest trauma. The presumed mechanism was interventricular septal dissection
      and formation of a pseudoaneurysm that ruptured after a delay. Echocardiography
      enabled a non-invasive diagnosis and follow-up of the patient.

PMID- 7721491
TI  - The Jervell and Lange-Nielsen syndrome.
AB  - The association of prolongation of the QT interval with recurrent attacks of
      syncope, sudden death, and malignant ventricular arrhythmias is known as the long
      QT syndrome. The syndrome may be familial with or without congenital deafness, or
      idiopatic. The syndrome with deafness (Jervell and Lange-Nielsen syndrome) is
      inherited through an autosomal recessive mechanism. In this study, we attempted
      to identify patients with the Jervell Lange-Nielsen syndrome amongst 154 deaf
      mute school children. Two patients had a corrected QT interval of 0.52 and
      congenital sensorineural hearing loss with the other electrocardiographic changes
      characteristic of the syndrome, such as inverted or bifid T wave. There was no
      evidence of electrocardiographic (ECG) abnormality in family members, except only
      one case of parental deafness. This is the first and preliminary report that
      analyzed the incidence of the Jervell and Lange-Nielsen syndrome amongst 154 deaf
      mute school children in Turkey. Our study was conducted to identify patients with
      this syndrome amongst children of another deaf mute school in Turkey.

PMID- 7721492
TI  - Spontaneous coronary artery dissection in a young woman resulting from an intense
      gymnasium "work-out".
AB  - We report on a young housewife who developed a spontaneous coronary artery
      dissection following unusually severe exercise. She survived an extensive
      anterior myocardial infarction with the help of an emergency coronary artery vein
      graft. This rare diagnosis must be considered when a young woman presents with an
      acute myocardial infarction.

PMID- 7721493
TI  - Anti-arrhythmic effect of converting enzyme inhibitor, enalapril in congestive
      heart failure: possible contribution of altered sympathovagal autonomic balance
      on the heart.

PMID- 7721494
TI  - Reliability of echocardiography for the evaluation of VSD anatomy in tetralogy of
      Fallot.

PMID- 7721495
TI  - Noninvasive testing in the diagnosis and management of unstable angina.
AB  - Patients presenting with a clinical diagnosis of unstable angina comprise a
      heterogenous population and a wide spectrum of patients with varying degrees of
      underlying coronary artery disease, severity and prognosis are categorized in
      this syndrome. A very small number of patients with unstable angina who are
      refractory to adequate in-hospital medical therapy should undergo urgent coronary
      angiography and, if suitable, revascularization. The vast majority of patients
      do, however, stabilize on medical therapy and an invasive approach, such as a
      coronary angiography should not be performed routinely to all of these patients.
      Early recognition of clinical and non-invasive test variables indicating an
      adverse outcome is of paramount importance in unstable angina. This review
      focuses on the importance of baseline clinical markers and the usefulness of a
      non-invasive approach with exercise testing, myocardial perfusion imaging, stress
      echocardiography, and Holter monitoring in the diagnosis, risk stratification,
      and management of patients with unstable angina.

PMID- 7721496
TI  - Percutaneous transluminal coronary angioplasty: refining standards for good
      practice.

PMID- 7721497
TI  - Diastolic function in patients with coronary artery disease: effect of angina and
      heart failure functional class.
AB  - The diastolic function of left and right parts of the heart using left and right
      mechanocardiogram method was investigated in 69 male patients with coronary
      artery disease and preceding myocardial infarction and in 18 normal patients.
      Nine patients were in angina class I, 28 were in class II, 32 were in class III.
      Forty-seven patients were in heart failure class II and 22 were in class III. The
      duration of isometric relaxation and atrium wave in left and right
      mechanocardiograms was more, and rapid filling wave was less in patients after
      myocardial infarction than in the control group. The duration of isometric
      relaxation and of atrium wave in left mechanocardiogram was more, and the
      duration of rapid filling wave was less in patients with heart failure class III
      than in patients in class II. The duration of isometric relaxation was more and
      the duration of rapid filling wave was less in right mechanocardiogram in
      patients with heart failure class III than in patients in class II. The diastolic
      abnormalities correlate more with the severity of heart failure than the angina
      severity. The diastolic abnormalities in right mechanocardiogram were found in
      patients without clinical manifestations of right ventricle failure.

PMID- 7721498
TI  - Which drug to choose for stable angina pectoris: a comparative study between
      bisoprolol and nitrates.
AB  - The choice between beta-blockade or nitrates as first line treatment for stable
      angina pectoris is based upon the different mechanisms of action and patient
      characteristics. We performed a clinical trial comparing the efficacy of the
      longacting beta-blocker bisoprolol once daily and the short acting nitrate,
      isosorbide dinitrate, three times daily in the reduction of anginal complaints in
      daily life and under stress. Thirty patients were enrolled in a double-blind
      randomised cross-over study. Both bisoprolol and isosorbide dinitrate were
      effective in reducing anginal attacks and nitroglycerin consumption
      significantly, but bisoprolol was significantly more effective than isosorbide
      dinitrate. Bisoprolol improved the workload during bicycle exercise testing
      significantly, but the improvement with isosorbide dinitrate was not significant.
      Despite the reduction in maximal rate pressure product, bisoprolol was
      significantly (P < 0.05) more effective at improving total workload and reducing
      the time to onset of angina than isosorbide dinitrate. The rate pressure product
      did not change significantly with isosorbide dinitrate. In this study, bisoprolol
      10 mg once daily was more effective and caused less side effects than isosorbide
      dinitrate 20 mg three times a day. It seems questionable if monotherapy of
      isosorbide dinitrate 20 mg t.i.d is an adequate drug regime for stable angina
      pectoris.

PMID- 7721499
TI  - Enalapril improves heart failure induced by monocrotaline without reducing
      pulmonary hypertension in rats: roles of preserved myocardial creatine kinase and
      lactate dehydrogenase isoenzymes.
AB  - We investigated the redistribution of myocardial isoenzymes of creatine kinase
      (CK) and lactate dehydrogenase (LD) in rats with right heart failure induced by
      monocrotaline and assessed the effect of enalapril, an angiotensin converting
      enzyme inhibitor. Wistar rats were divided into four groups: (1) control (n =
      20), (2) control + enalapril (25 mg/kg/day) (n = 22), (3) monocrotaline (50
      mg/kg) (n = 45), (4) monocrotaline (50 mg/kg) + enalapril (25 mg/kg/day) (n =
      32). After 4 weeks, the monocrotaline group developed severe pulmonary
      hypertension and right ventricular hypertrophy with marked decrease in myocardial
      norepinephrine and increase in both plasma atrial natriuretic peptide and
      mortality rate (33.3%). The marked decrease in both MM and mitochondrial CK
      ('creatine shuttle') and the relatively constant BB and MB CK caused the net
      depression of total CK. The depression of LD1 (aerobic LD) was remarkable
      compared with the relatively constant total LD. In the monocrotaline+enalapril
      group, mortality rate (9.4%), cardiac hypertrophy and plasma atrial natriuretic
      peptide were all significantly reduced and myocardial norepinephrine recovered
      although pulmonary hypertension was not improved at all. However, myocardial
      total, MM and mitochondrial CK and LD1 activities were all recovered completely
      or partially in this group. Thus, enalapril reduced cardiac hypertrophy and
      failure and improved the prognosis in this model of pulmonary hypertension. This
      beneficial effect of enalapril was not associated with pulmonary vasodepression
      but with the inhibition of myocardial isoenzyme redistribution of CK and LD, i.e.
      the preservation of 'creatine shuttle' and aerobic LD.

PMID- 7721500
TI  - Vessel dilator is associated with survival after acute myocardial infarction.
AB  - To assess whether infarct size, ischemic area and/or survival correlates with
      circulating atrial natriuretic peptides (long acting sodium stimulator, vessel
      dilator, or atrial natriuretic factor), these peptides were measured in a canine
      model of acute myocardial infarction. Elevations in the circulating
      concentrations of atrial natriuretic factor, vessel dilator, and long acting
      sodium stimulator were significant (P < 0.05) within 6 min of coronary occlusion
      of the left anterior descending coronary artery. The percentage of ischemic
      myocardium ranged from 20 to 67% with a mean of 37 +/- 17%. The area of
      infarction ranged from 1 to 13% with the infarcted area of non-survivors being
      twice that of survivors. Both the ischemic and infarcted areas correlated (P <
      0.05) with the circulating concentrations of these atrial natriuretic peptides.
      Survival correlated also with the circulating plasma concentrations of vessel
      dilator, atrial natriuretic factor and long acting sodium stimulator (P < 0.05).
      When these circulating concentrations were evaluated, however, by determining
      their area under their respective concentrations curves and expressing each as
      the log area under plasma concentration-time curve (area under the curve) per kg
      of weight (Y = 58.48X-23.62; r = 0.825; P = 0.0009), vessel dilator was the only
      atrial natriuretic peptide that correlated with survival.

PMID- 7721501
TI  - Epidemiologic study of diet and coronary risk factors in relation to central
      obesity and insulin levels in rural and urban populations of north India.
AB  - In a population survey of 162 rural and 152 urban subjects aged 26-65 years at
      Moradabad, the findings are compared with existing data on Indian immigrants to
      Britain and United States. In comparison with rural subjects, urban subjects had
      a higher prevalence of coronary artery disease (8.6 vs. 3.0%) and diabetes (7.9
      vs 2.5%), higher blood pressures, total and low density lipoprotein cholesterol,
      triglycerides and postprandial 2-h blood glucose and plasma insulin similar to
      observations made in UK in immigrants compared to Europeans. Fasting plasma
      insulin and high density lipoprotein cholesterol levels in urban subjects were
      comparable with rural subjects. Mean body weights were significantly higher in
      urban women, but not in men, than in rural subjects. However the body mass index
      (22.9 +/- 4.2 vs. 21.6 +/- 2.4 kg/m2) and waist-hip girth ratio (0.89 +/- 0.10
      vs. 0.86 +/- 0.07) were significantly higher in urban men compared to rural men
      without such differences in women. Underlying these differences in risk factors,
      urban subjects had three times better socioeconomic status than rural subjects
      and were eating higher total and saturated fat, cholesterol and refined
      carbohydrates and lower total and complex carbohydrates compared to rural men and
      women. Energy expenditure during routine and spare time physical activity was
      significantly higher in rural compared to urban subjects. Those patients who had
      risk factors, showed lesser physical activity and had greater adverse factors in
      the diet compared to subjects without risk factors. Body mass index and waist-hip
      girth ratio in patients with risk factors were significantly higher than in
      subjects without risk factors. The findings suggest that decreased consumption of
      total and saturated fat and increased physical activity may be useful for
      prevention of coronary artery disease among urbans as well as in immigrants.

PMID- 7721502
TI  - Taking antihypertensive medication--controlling or co-operating with patients?
AB  - Low compliance with antihypertensive drug regimens has been a well documented
      reason for inadequate control of hypertension. We assessed recent literature
      regarding compliance from different disciplines to clarify the nature of reported
      problems on low compliance to prescribed antihypertensive medication. Much
      research focuses on primary factors for compliance, methods to monitor and
      measure individual rates and patterns of compliance. From a behavioural oriented
      point of view, the focus is on understanding why patients act as they do. This
      review indicates that there is an almost complete lack of knowledge about how the
      decision making in the clinical practice is organized when prescribing
      antihypertensive medication and/or when following up treatment from patients
      already taking such drugs. Since the concrete communication and collaboration
      between patient and physician in the clinical setting are of prime significance
      for patient adherence to drug regimens, it is important to shed light on what
      happens in this critical situation.

PMID- 7721503
TI  - Echocardiography of sinus of Valsalva aneurysm with rupture into the right
      atrium.
AB  - Before the advent of modern techniques, diagnosing unruptured sinus of Valsalva
      aneurysm in the living patient was rare, with most of the reports coming from
      autopsy or surgery. Once rupture occurs however, characteristic symptoms and
      signs, such as precordial distress, a continuous murmur over the base of the
      heart, pulmonary congestion, and congestive heart failure, usually occur rather
      abruptly. We describe a case of ruptured aneurysm of the non-coronary sinus of
      Valsalva diagnosed by transthoracic echocardiography and Doppler as a single
      examination for quickly establishing a correct diagnosis in patients with a new
      continuous murmur.

PMID- 7721504
TI  - Diagnostic accuracy of echocardiography-Doppler in acute pulmonary embolism.
AB  - We studied prospective recording of clinical, electrocardiographic, Doppler and
      echographic parameters in 32 patients with proven pulmonary embolism, matched
      with 32 patients with clinically suspected pulmonary embolism and normal
      perfusion scan or angiography. Thirty-seven per cent of cases and 16% of control
      subjects had clinical signs of right ventricular overload; S1-Q3-T3 ECG pattern
      was found in 11 cases and one control. Other clinical and ECG parameters did not
      reach significant difference. Echographic septum motion was abnormal in 42% of
      cases and 9% of controls (P < 0.05), end-diastolic right ventricular diameter was
      > 25 mm in 67% of cases and 11% of controls, ratio of end-diastolic right over
      left ventricular diameters increased over 0.6 in 67% of cases and 11% of
      controls, while Doppler examination found tricuspid regurgitant peak flow
      velocity > 2.5 m/s in 84% of cases vs. 10% of controls. According to these
      parameters, Doppler-echocardiography was normal in 6% of cases and 87% of control
      subjects (P < 0.001 for each). In suspected pulmonary embolism, our study shows
      that Doppler-echocardiography may be both sensitive and specific in emergency
      conditions and help the decision making for further invasive investigations.

PMID- 7721505
TI  - Right atrial metastasis as primary clinical manifestation of hepatocellular
      carcinoma.
AB  - We present an 81-year-old man with right atrial metastasis associated with
      hepatocellular carcinoma. Antemortem diagnosis was made by two-dimensional
      echocardiography, cardiac catheterisation and computed tomography, followed by
      surgical intervention and histological examination of the right atrial tumour. To
      our knowledge, this is the second case with intravital diagnosis and histological
      confirmation.

PMID- 7721506
TI  - Sino-atrial Wenckebach conduction in thyrotoxic periodic paralysis: a case
      report.
AB  - A 28-year-old male presented with thyrotoxic periodic paralysis. On admission to
      hospital the serum potassium level was 1.4 mmol/l. The ECG showed classical
      features of hypokalaemia. In addition, sino-atrial block with Wenckebach
      conduction was also present. With the normalization of the serum potassium, the
      ECG became completely normal and showed no evidence of any arrhythmia.

PMID- 7721507
TI  - Selective ergonovine-induced coronary artery spasm and ST-segment alternans after
      blunt thoracic trauma.
AB  - A 24-year-old man was found to have angiographically normal coronary arteries
      shortly after suffering blunt thoracic trauma. Selective ergonovine
      administration into the left coronary artery induced total occlusion of the left
      anterior descending branch and electrical alternans of the ST-segment. This case
      demonstrates coronary artery spasm as a possible mechanism of coronary occlusion
      after blunt thoracic trauma.

PMID- 7721508
TI  - Absence of the left pericardium diagnosed by computed tomography.
AB  - A case report of left pericardial absence in a 12-year-old boy is described. The
      suspected diagnosis was not shown either by cross-sectional echocardiography or
      angiography, but was correctly established by computed tomography (CT), showing
      the effectiveness of this diagnostic test for diagnosis of pericardial defects.

PMID- 7721509
TI  - Acute myocardial infarction in a young man after heat exhaustion.
AB  - A 33-year-old man with heat exhaustion was admitted to our hospital suffering
      from severe chest pain. Serum creatine kinase elevation and new Q waves revealed
      myocardial infarction of the inferior wall. Technetium-99m-pyrophosphate
      suggested diffuse myocardial damage, although the left ventricular function was
      normal by echocardiography. This case highlights the importance of early
      recognition of heat stroke and heat exhaustion, as they are associated with
      widespread tissue injury.

PMID- 7721510
TI  - The capture-recapture method for estimation of cancer registry completeness: a
      useful tool?
AB  - BACKGROUND: In this paper we investigated whether the capture-recapture method is
      useful for a cancer registry to monitor its completeness of case ascertainment on
      a routine basis. METHODS: The capture-recapture method was used to estimate the
      completeness of case ascertainment in three regional cancer registries in the
      Netherlands, which are based on case finding by pathology laboratories and
      hospitals. RESULTS: Completeness was estimated to be 98.3%. The estimate of
      completeness was dependent on age and cancer site, with lower estimates of
      completeness for skin cancer and lymphatic and haematopoietic malignancies and
      for the age group > or = 75 years. CONCLUSIONS: A major drawback of the capture
      recapture method is its inability to estimate the number of cases that are not
      routinely notified to the registry by one or both notification sources. Another
      limitation is the lack of statistical power to detect incompleteness in an early
      stage. It is concluded that the capture-recapture method is not useful for
      everyday surveillance of completeness in cancer registration.

PMID- 7721511
TI  - Trends in incidence of various cancers in Bulgaria, 1981-1990.
AB  - BACKGROUND: Bulgaria has undergone considerable social changes in the last 40
      years, including a transition from a 75% rural to a 75% urban population. These
      changes might be expected to be reflected in disease rates. The Bulgarian cancer
      registry has computerized data on cancer incidence throughout the country from
      1981 onwards. METHODS: Incidence rates in Bulgaria from 1981 to 1990 of cancers
      of the lung, stomach, large bowel, prostate and bladder in males and of cancers
      of the breast, lung, stomach, large bowel, cervix and corpus uteri in females
      were analysed with particular attention to time trends, age-specific changes in
      rates and urban/rural differences. Poisson regression was used for statistical
      analysis. RESULTS: Male rates of cancers of the lung, large bowel, prostate and
      bladder increased significantly over the period, with average annual increases of
      0.4%, 2.9%, 1.3% and 2.3% respectively. In females, rates of cancers of the
      breast, cervix and corpus uteri increased significantly, with average annual
      increases of 1.3%, 1.9%, and 2.9%. In both sexes, stomach cancer incidence
      declined significantly, by 3.0% per year for males and 3.6% per year for females.
      Rural rates were lower than urban rates for most cancers, particularly in the
      higher age groups. The decline in male stomach cancer rates was confined to rural
      areas. The increases in rates of lung cancer and prostate cancer in males and of
      colorectal cancer and breast cancer in females were most rapid in urban areas.
      CONCLUSIONS: Substantial changes in rates of various cancers have taken place
      from 1981 to 1990, in particular increases in rates of breast cancer and large
      bowel cancer in women resident in urban areas. It is suggested that dietary
      changes may be responsible for some of these changes.

PMID- 7721512
TI  - Correlation of cervical cancer mortality with reproductive and dietary factors,
      and serum markers in China.
AB  - BACKGROUND: Cervical cancer is the second leading cause of cancer death among
      Chinese women. Within China, a considerable geographical variation in mortality
      rates has been observed, but the reasons are not well understood. METHODS:
      Cervical cancer rates were examined in relation to indices of reproductive
      factors, dietary habits, and selected serum biomedical markers in 65 rural
      Chinese counties. RESULTS: Cervical cancer mortality rates correlated positively
      and significantly with antibodies to herpes simplex virus type 2 (HSV-2) (r =
      0.40, P < 0.01), serum levels of ferritin (r = 0.33, P < 0.01), body mass index
      (BMI) (r = 0.42, P < 0.01) and cigarette smoking (r = 0.51, P < 0.05) and
      negatively and significantly with age at first birth (r = -0.51, P < 0.01),
      consumption of green vegetables (r = -0.40, P < 0.01) and animal foods (r = 
      0.40, P < 0.01), and serum levels of selenium (r = -0.26, P < 0.05). When these
      variables were considered in the multiple regression analysis, early age at first
      birth and higher BMI were positively associated with cervical cancer mortality,
      while consumption of green vegetables and animal foods were negatively
      correlated. In the serum model, infection with HSV-2 and low levels of sex
      hormone binding globulin (SHBG) were positively related to cervical cancer
      mortality. No relation was found for consumption of fruits. CONCLUSIONS: Although
      limitations of these ecologic data preclude causal inferences, findings in this
      study, including associations with HSV-2 infection, early age at first birth,
      consumption of green vegetables and animal foods, may provide clues to cervical
      cancer aetiology.

PMID- 7721513
TI  - Sunlight, vitamin D, and ovarian cancer mortality rates in US women.
AB  - BACKGROUND: In general, ovarian cancer incidence and mortality is higher in
      northern than southern latitudes. This ecologic study tests the hypothesis that
      vitamin D produced in the skin from sunlight exposure may be associated with a
      protective action in ovarian cancer mortality. METHODS: The association between
      average annual sunlight energy and age-specific ovarian cancer mortality rates in
      counties containing the 100 largest US cities was evaluated for 1979-1988. Simple
      linear regression was performed by decade using sunlight and ozone as independent
      variables and ovarian cancer rates as the dependent variable. Multiple regression
      was used to adjust for ozone and sulphur dioxide, since these atmospheric
      components may absorb ultraviolet light. RESULTS: Fatal ovarian cancer in these
      areas was inversely proportional to mean annual intensity of local sunlight in a
      univariate analysis (P = 0.0001), and in a regression adjusted for air pollution
      (P = 0.04). The association was also seen when restricted to 27 major urban areas
      of the US; however, probably due to a small sample size, this statistic did not
      reach significance. CONCLUSIONS: This ecologic study supports the hypothesis that
      sunlight may be a protective factor for ovarian cancer mortality.

PMID- 7721514
TI  - The role of tobacco, alcohol use, and body mass index in oral and pharyngeal
      cancer.
AB  - BACKGROUND: Although tobacco smoking and alcohol drinking are well-established
      risk factors for oral cancer, relatively few studies have addressed the
      comparative effect of filter versus non-filter cigarettes, the nature of the
      reduction in risk following cessation, and the joint effects of tobacco and
      alcohol. In addition, recent studies suggest an inverse association of body mass
      index with oral cancer. We used data from a large, hospital-based case-control
      study to investigate these issues. METHODS: The data set consisted of 1097 male
      and 463 female oral cancer cases and 2075 male and 873 female controls.
      Unconditional logistic regression was used to estimate the effect of risk factors
      in the presence of covariates. RESULTS: Among male current smokers, users of
      filter cigarettes (whether lifetime users or those who switched to filter
      cigarettes) had a significantly reduced risk of oral cancer which approached 50%.
      Among female current smokers, only those who switched to filter cigarettes
      10+years previously showed a significantly reduced risk. Those who quit smoking
      experienced a marked decrease in risk compared to current smokers. Smoking and
      alcohol consumption showed a significant interaction on a multiplicative model.
      After adjustment for covariates, leanness was significantly associated with oral
      cancer among male current and ex-smokers. CONCLUSIONS: The results of this study:
      1) indicate that smokers of filter cigarettes and those who quit smoking are at
      substantially reduced risk of oral cancer, 2) demonstrate interaction between
      smoking and drinking, and 3) suggest that leanness preceding diagnosis may be
      associated with oral cancer.

PMID- 7721515
TI  - Occupational exposure to polycyclic aromatic hydrocarbons and the risk of bladder
      cancer: a French case-control study.
AB  - BACKGROUND: The risk of bladder cancer has been shown to be increased in
      occupations which are likely to involve exposure to polycyclic aromatic
      hydrocarbons (PAH), but up to now, most studies have considered this exposure in
      terms of job title. METHODS: A hospital-based case-control study of 658 male
      cases of bladder cancer and 658 male controls was carried out in five areas of
      France from 1984 to 1987. For each subject, occupational exposure to PAH was
      assessed from questionnaires by an expert according to a semi-quantitative index
      of exposure. RESULTS: The overall odds ratio for PAH exposure, adjusted for
      smoking, coffee drinking and occupational exposure to aromatic amines was
      estimated at 1.3 (95% CI: 1.0-1.7, P < 0.05). A slight but clear dose-response
      relationship was observed, and the trend remained significant after adjustment
      for cumulative smoking, with odds ratios of 1.2 (95% CI: 0.9-1.7), 1.4 (95% CI:
      0.9-2.2) and 1.8 (95% CI: 0.8-3.9) for low, medium and high average exposures
      respectively compared to subjects unexposed to PAH (P for trend < 0.05).
      Moreover, the association between bladder cancer and PAH exposure was also
      investigated in a category of smokers homogeneous with respect to their tobacco
      consumption. In this heavy-smoker group, a stronger association with PAH was
      detected. CONCLUSIONS: These results support the hypothesis of a causal
      relationship between occupational exposure to PAH and bladder cancer risk.

PMID- 7721516
TI  - Physical activity and cardiovascular risk factors in rural Shanghai, China.
AB  - BACKGROUND: Data on the association between physical activity and cardiovascular
      risk factors among populations with a relatively high level of physical activity
      such as the Chinese, are sparse. METHODS: In 1991, as part of the Sino-Shanghai
      Cardiovascular Disease Registry Project, a cross-sectional survey was performed
      in a random sample of 1206 residents, aged 35-64 years, living in rural Shanghai,
      China. Information on physical activity was obtained by questionnaire. The level
      of physical activity was categorized into low, moderate and high, based on the
      presence of a weekly frequency (< 1, 1-2, > or = 3) of periods of 20 minutes that
      cause shortness of breath, increase in pulse rate and perspiration. Body mass
      index (BMI), systolic (SBP) and diastolic blood pressure (DBP) level, serum
      lipids levels, smoking status and heart rate were assessed. RESULTS: Across
      groups with low, moderate and high levels of physical activity, significant
      inverse trends were found for hypertension, total cholesterol, BMI and heart rate
      in men, and for hypertension, SBP and DBP, BMI and heart rate in women. High
      density lipoprotein cholesterol and current smoking were not related to physical
      activity. When differences in BMI were allowed for, the association between
      physical activity and hypertension and serum cholesterol in men, and with
      hypertension, SBP and DBP in women, were attenuated. CONCLUSIONS: Our findings
      from a population-based survey in China suggest that a high level of physical
      activity is associated with favourable levels of some of the established
      cardiovascular risk factors in men and women.

PMID- 7721517
TI  - Snoring and risk of stroke and ischaemic heart disease in a 70 year old
      population. A 6-year follow-up study.
AB  - BACKGROUND: A number of studies have demonstrated an association between habitual
      snoring and cardiovascular morbidity and mortality. Control for the influence of
      potential confounders has been inadequate. To clarify the issue we examined the
      association between snoring and future risk of ischaemic heart disease (IHD) and
      stroke while controlling for the potential influence of major cardio- and
      cerebrovascular risk factors. METHODS: In all, 804 70 year old males and females
      were classified according to snoring habits. Alcohol and tobacco consumption,
      blood pressure, body mass index, social group, plasma lipids (triglycerides,
      cholesterol, high density lipoprotein), fasting blood glucose, plasma epinephrine
      and norepinephrine were determined at baseline. RESULTS: Over a 6-year period
      (1984-1990) 88 suffered an IHD episode, 60 had a stroke and 180 died. A slightly
      higher stroke incidence was found among snorers (relative risk [RR] = 1.8; (95%
      confidence interval: 1.1-3.6). When adjustments were made for the above
      confounders, no associations could be found between snoring and IHD, stroke or
      all-cause mortality. CONCLUSIONS: In a 70 year old population, snoring is not
      associated with an increased risk of IHD, stroke or all-cause mortality.

PMID- 7721518
TI  - Mortality following radiation treatment for infertility of hormonal origin or
      amenorrhoea.
AB  - BACKGROUND: Between 1920 and 1965, radiation treatment to the ovaries and/or
      pituitary gland was used for refractory hormonal infertility and amenorrhoea. The
      potential carcinogenic effects of hormonal infertility, as well as exposure to
      relatively low doses of ovarian and pituitary radiation can be studied among
      patients receiving these treatments. METHODS: A cohort of 816 patients treated
      between 1925 and 1961 was identified from the medical records of a New York City
      radiologist. The mortality experience for 84% of these women was determined and
      radiation doses for individual patients were estimated. Doses were, on average,
      87, 64, 54, and 29 cGy to the ovary, brain, colon, and active bone marrow,
      respectively. RESULTS: Compared with mortality rates in the US population, the
      risk of death was less than expected (standardized mortality ratio [SMR] = 0.87;
      95% confidence interval [CI]: 0.75-1.00). Deaths due to circulatory and digestive
      diseases were significantly below expectation. Cancer mortality was about 10%
      higher than that expected based on New York City mortality rates. Based on a
      small number of cases, no increase was found for cancers of the ovary or brain,
      or leukaemia, sites for which direct radiation exposure occurred, but significant
      excesses of colon cancer and non-Hodgkin's lymphoma were observed. A deficit in
      mortality from female genital cancers was surprising, since nulliparity has been
      a consistently reported risk factor for cancers of the endometrium and ovary.
      Breast cancer mortality was close to expectation. CONCLUSIONS: Overall, this
      study provided little evidence that either infertility or its treatment with
      radiation increased the risk of total or cancer mortality.

PMID- 7721519
TI  - High mortality in the Thule cohort: an unhealthy worker effect.
AB  - BACKGROUND: The objective was to study mortality in the Thule cohort in order to
      clarify whether it is a selected population and to ascertain the possibility of
      misinterpretation when national mortality rates are used as reference in the
      analysis of occupational mortality. METHODS: The cohort consists of 4322 Danish
      men who were employed between 1963 and 1971 at the Thule air base in Greenland.
      One part of the cohort were employed during the clean-up period after the crash,
      in 1968, of a US bomber carrying nuclear weapons, the other part had been
      employed only outside the clean-up period. The cohort was followed up until 1992.
      RESULTS: After 30 years of follow-up, SMR was 1.38 for all causes (95% confidence
      interval [CI]: 1.28-1.49), 1.25 for cancer (95% CI: 1.07-1.45), 1.17 for
      circulatory diseases (95% CI: 1.01-1.34), 1.58 for other natural causes (95% CI:
      1.35-1.84), and 1.46 for violent deaths (95% CI: 1.22-1.74). Marked excess
      mortality measured by SMR was found from lung cancer 1.70, AIDS 3.55, alcoholism
      4.04, cirrhosis of the liver 2.45, symptoms and ill-defined conditions 1.93, and
      suicide 1.63. The SMR was 1.09 for the age group 17-24 at entry, 1.42 for the age
      group 25-34, and 1.45 for the age group > or = 35. CONCLUSIONS: The high
      mortality and the mortality pattern in the Thule cohort shows strong evidence for
      selection and provides strong support for the suggestion that these workers
      constitute a group in poor health probably caused by lifestyle. The study
      demonstrates that an incomplete analysis (i.e., one limited to a subgroup of
      workers involved in the radiation clean-up) could lead to spurious conclusions
      about hazardous occupational exposures.

PMID- 7721520
TI  - Socioeconomic and anthropometric status, and mortality of young children in rural
      Bangladesh.
AB  - This article investigates the interrelationship of socioeconemic status,
      anthropometric status and mortality of young children in rural Bangladesh. Data
      for this study come from Matlab, the vital registration area of the International
      Centre for Diarrhoeal Disease Research, Bangladesh, where anthropometric and
      socioeconomic data concerning 1976 children aged 12-23 months were collected in
      November-December 1975. From these data, anthropometric indices are created, and
      the relationships of socioeconomic status measured by dwelling space and
      anthropometric indices with mortality during the 2 years following measurement of
      these children are investigated. It is found that both socioeconomic status and
      anthropometric indices are related to mortality. However, the relationship of
      anthropometric indices is much stronger. Among the anthropometric indices
      considered, weight-for-age, height-for-age and arm circumference reflect
      socioeconomic status better than weight-for-height does; and, the first three
      indices are equally good, and individually better than weight-for-height, as
      predictors of mortality. The degree of the effect of socioeconomic status
      (dwelling space) on mortality explained by the best performing anthropometric
      index, weight-for-age, was not more than 25%. It is concluded that an
      anthropometric index that can classify socioeconomic status more efficiently is a
      better predictor of 2-year mortality than any other anthropometric index.

PMID- 7721521
TI  - Clustering of attempted suicide: New Zealand national data.
AB  - BACKGROUND: The extent to which clusters of attempted suicides occur is a
      significant problem that is complementary to the current available research on
      the clustering of completed suicide. However, little systematic research on
      clusters of attempted suicides exists. The present study examines the extent and
      nature of clustering of suicide attempts. METHOD: The occurrence of clustering of
      attempted suicide was examined in nationwide data for all New Zealand hospitals,
      obtained from the New Zealand Health Statistics Services for the years 1988-1990.
      The Scan statistic and Knox procedure were employed for testing the significance
      of clusters in time and time-space, respectively. RESULTS: The analyses indicated
      that significant time clustering occurred in younger age groups, specifically
      among 15-19 and 20-24 year olds. The results could not be accounted for by
      seasonal variations in admissions. Age specificity of time-space clusters
      emerged, exhibiting a similar pattern to that reported for completed suicides in
      the US. CONCLUSIONS: The results suggest a similar underlying mechanism for the
      clustering of parasuicide and completed suicides and provide support for the
      existence of contagion of suicidal behaviour. The implications for prevention are
      discussed.

PMID- 7721522
TI  - The Sick Building Syndrome (SBS) in office workers. A case-referent study of
      personal, psychosocial and building-related risk indicators.
AB  - BACKGROUND: The Office Illness Project in Northern Sweden, comprising both a
      screening questionnaire study of 4943 office workers and a case-referent study of
      Sick Building Syndrome (SBS) in 464 subjects was recently completed. Previously
      published results from the survey showed that female gender asthma/rhinitis, high
      psychosocial work load, paper and visual display terminal (VDT) work were related
      to an increased prevalence of SBS symptoms. METHODS: The case-referent study
      presented in this paper used data from the questionnaire supplemented with
      information from a clinical examination, a survey of psychosocial factors at work
      building data from inspection and measurements taken at the work sites. RESULTS:
      Personal factors such as atopy and photosensitive skin, psychosocial conditions
      and physical exposure factors influencing indoor air quality (IAQ), such as
      outdoor air flow rates and the presence of photocopiers were related to an
      increased prevalence of the reported SBS symptoms. The results were established
      using multivariate analysis. CONCLUSIONS: The rate response relationship between
      actually measured ventilation rates and the prevalence of perceived SBS symptoms
      presents strong evidence for the association between IAQ factors and health.

PMID- 7721523
TI  - Changing patterns in the epidemiology and hospital care of peptic ulcer.
AB  - BACKGROUND: Our aim was to study trends in hospital admission rates for peptic
      ulcer in a geographically defined population, and to distinguish the effects of
      period, age and birth cohort on the rates. METHODS: Analysis of linked, routinely
      collected abstracts of hospital inpatient care held by the Oxford record linkage
      study for the period 1970-1986. Age- and sex-specific and age-standardized
      hospitalization, readmission and operation rates were calculated for patients
      with peptic ulcer. Age, cohort and period effects were examined using log-linear
      models. RESULTS: Records for a total of 5462 people with gastric ulcer and 10,186
      with duodenal ulcer were identified. Overall, the age-standardized admission
      rates for both gastric and duodenal ulcer declined over the study period. The
      decrease was confined to people < 65 years of age. Among elderly patients
      admission rates for peptic ulcer increased over time, more so in females than in
      males. Admission rates were higher in the elderly than in young people for both
      gastric and duodenal ulcer. The apparent age effect was, in fact, mainly
      attributable to a birth cohort effect: age-specific admission rates were lower in
      people born after 1925 than in people born at the beginning of the century. This
      was more marked for males than females. There was a considerable decline in major
      operations undertaken on peptic ulcer; admission rates for endoscopy increased;
      and readmission rates did not show significant changes. CONCLUSIONS: The overall
      decline found for hospital care of peptic ulcer during the study period is
      consistent with that found in England for mortality rates ascribed to peptic
      ulcer. The cohort effect found in the data for hospitalized morbidity supports
      that reported by others for mortality. The cohort effect indicates that the
      decline was related more to changes in risk factors in the cohorts born in
      different periods than to the introduction of new pharmacological treatments
      since the 1970s.

PMID- 7721524
TI  - Differential misclassification of alcohol and cigarette consumption by pregnancy
      outcome.
AB  - BACKGROUND: The validity of the results of studies using retrospectively
      collected information on exposures is often criticized, because cases may report
      differently from controls even if their true exposure status is the same. This
      study was performed to quantify the extent to which this effect (differential
      misclassification) may occur for alcohol and cigarette consumption by pregnancy
      outcome. METHODS: Prospective as well as retrospective information on alcohol and
      cigarette consumption was collected for 2806 mothers resident in all 12 provinces
      of the Netherlands, who gave birth between 1978 and 1979. Changes in mean
      reported consumption and changes from user to non-user based on retrospective and
      prospective information were compared for cases and controls. This was done by
      calculating absolute differences (retrospective minus prospective) in reported
      consumption and by calculating 'misclassification odds ratios'. Further,
      conventional odds ratios based on retrospective information were compared with
      those based on prospective information. Outcome measures were stillbirth, small
      for gestational age (SGA), congenital malformations, preterm birth and low
      birthweight. RESULTS: The only statistically significant result was found for
      smoking and SGA. Mothers with an SGA child retrospectively reported a higher
      number of cigarettes smoked than they had prospectively, more so than mothers of
      a control child. However, the odds ratios of the relation between SGA and smoking
      based on prospective and retrospective information, respectively, were virtually
      the same. CONCLUSIONS: Our results suggest that information bias is unlikely to
      have a large influence on effect estimates in studies using retrospective
      information on alcohol and cigarette consumption.

PMID- 7721526
TI  - Childhood onset diabetes--time trends and climatological factors.
AB  - BACKGROUND: Childhood diabetes has been shown to have increased over time, to
      have a north-south gradient within Sweden and to exhibit seasonal variation. In
      the present study we have analysed the variation in incidence of childhood
      diabetes with time, and climatological factors such as mean temperature and
      sunshine hours. METHODS: The Swedish childhood diabetes register prospectively
      records all incident cases of diabetes with onset at 0-14 years since 1 July
      1977. By 1 January 1993, 5831 cases had been registered. The data set was
      analysed using Poisson regression modelling and Cox' proportional hazards model.
      RESULTS: The mean annual incidence rate was 25/100,000. Over the 15 years there
      was an overall increase with time. When analysing the first 7 years and the last
      8 years separately the basal linear increase was a mean 6% per year during the
      first period but no significant increase was noted during the second period. The
      increase during the first period was mainly due to an increase in incidence
      before the age of 10. Significant inverse and independent relationships were
      found between incidence rate and mean sunshine hours and mean temperature,
      respectively, when measured monthly in each county. We did not find any
      association between the climatological factors and age at onset. CONCLUSIONS: The
      increasing trend in childhood diabetes in Sweden during the past 15 years was
      mainly due to an increase in incidence in children younger than 10 years of age
      with onset during the first half of the observation period. During the last 8
      year period incidence levelled off. A low mean temperature and a low number of
      sunshine hours are inversely and independently correlated to the incidence of
      childhood diabetes which may partly explain the north-south gradient and seasonal
      variation in the incidence of the disease.

PMID- 7721525
TI  - Comparison of heated water-filled mattress and space-heated room with infant
      incubator in providing warmth to low birthweight newborns.
AB  - BACKGROUND: Prevention of excessive heat loss is fundamental to survival of low
      birthweight (LBW) newborns. The use of infant incubators (INC) is beyond the
      resources of developing countries, and the space-heated room (SHR) has been the
      only feasible means of providing thermal protection to LBW newborns. Recently a
      thermostatically controlled, heated, water-filled mattress (HWM) has been
      developed as a potentially simpler and affordable alternative. METHODS: In a
      neonatal care ward of a referral hospital in Addis Ababa, 62 < 1 week old
      newborns, weighing 1000-1999 g, who were well enough to breathe comfortably in
      room air and tolerate oral feeds, were randomly allocated to INC, HWM or SHR and
      followed for 3 weeks. The level of cold stress as assessed by core-to-skin
      temperature gradient and the rate of weight gain were the main outcome measures.
      RESULTS: The level of cold stress was lowest in the INC, intermediate in the HWM
      and highest in the SHR. Relative to the INC group, the HWM group exhibited a
      modest increase in the occurrence of clinically important hyperthermic or
      hypothermic deviations in core temperature (rate ratio (RR) = 2.3; 95% CI: 0.9,
      5.6), and the SHR displayed a definite increase (RR = 4.0; 95% CI: 1.7, 9.3).
      During the first week, the rate of weight gain was highest in the INC group (3.6
      g/kg/day), lowest in the SHR group (-2.3 g/kg/day, P < 0.05 versus INC) and
      intermediate in the HWM group (1.6 g/kg/day, P > 0.1 versus INC). CONCLUSION:
      Care in the SHR produced clinically significant thermal stresses and was
      associated with deficient early neonatal growth, but the use of HWM may
      constitute a feasible and clinically acceptable alternative in providing warmth
      to LBW newborns during the neonatal period.

PMID- 7721527
TI  - Determinants of trunk abnormalities in adolescence.
AB  - BACKGROUND: The relationship between gender, anthropometric factors, adolescent
      growth, maturation and incidence of trunk abnormalities was studied in 2819
      children who were symmetric at baseline examination. METHOD: At age 11 years and
      at age 13 years, data on height, weight, onset of adolescent growth spurt,
      pubertal phase and menarche were collected and examination for trunk
      abnormalities was performed. Data analysis included calculation of 2-year
      cumulative incidence and relative risks (RR) of trunk abnormalities. RESULTS: Two
      year cumulative incidence was 11%. The RR for boys was 0.78 (95% confidence
      interval (CI): 0.63-0.96) compared to girls. Height was the strongest predictor
      for the development of trunk abnormalities in both sexes. The RR increased after
      adjustment for weight, onset of growth spurt, pubertal phase, and menarche. The
      RR was higher for girls with onset of adolescent growth spurt compared to girls
      who had not yet started their adolescent growth spurt (RR = 1.45, 95% CI: 1.08
      1.95). For girls who had reached menarche, the RR was 0.48 (95% CI: 0.24-0.96)
      compared to those who had not reached menarche. CONCLUSIONS: Our findings suggest
      that taller 11 year old girls with onset of adolescent growth spurt have
      increased risk of future trunk abnormalities, but that having reached menarche
      has a protective effect.

PMID- 7721528
TI  - Non-contraceptive hormones and the risk of rheumatoid arthritis in menopausal
      women.
AB  - BACKGROUND: Several reproductive factors appear to affect a women's risk of
      developing rheumatoid arthritis. This study's purpose was to determine whether
      use of non-contraceptive hormones is among them. METHODS: A population-based case
      control study was conducted in King County, Washington and Group Health
      Cooperative of Puget Sound, a prepaid health plan. New cases of rheumatoid
      arthritis in peri- or postmenopausal women (n = 135) were verified through
      clinical examination and compared with 592 controls. Both groups were interviewed
      in person about hormone use and demographic and reproductive factors. RESULTS:
      The age-adjusted relative risk (RR) among women who had ever used non
      contraceptive oestrogens was 1.04 (95% confidence interval [CI]: 0.70-1.55), and
      among women who had ever used progestins it was 0.66 (95% CI: 0.40-1.08). For
      current users of oestrogen only, the RR was 0.97 (95% CI: 0.62-1.53), and among
      current users of oestrogen plus progestin it was 0.81 (95% CI: 0.45-1.45).
      Multivariate analyses yielded similar results. There was little evidence of a
      dose-response relationship with duration of use or with frequency of progestin
      use. CONCLUSIONS: Use of non-contraceptive oestrogens appears to have little
      effect on the risk of developing rheumatoid arthritis in menopausal women. There
      may be a modest reduction in risk among progestin users.

PMID- 7721529
TI  - Incidence of dementia and Alzheimer's disease in elderly community residents of
      south-western France.
AB  - BACKGROUND: Dementia is a growing problem in developed countries. The aim of this
      paper is to estimate incidence rates of dementia, Alzheimer's disease and
      vascular dementia in a community population of South-Western France. METHODS: A
      sample of 2792 subjects was selected and followed-up 1 year and 3 after the
      initial screening. At each visit, a standardized questionnaire was administered
      by trained psychologists. Demented subjects were identified using a two-step
      procedure. The first step consisted of a systematic screening by the psychologist
      using DSM IIIR criteria for dementia. In the second step, subjects who fulfilled
      the DSM IIIR criteria were examined by a neurologist. NINCDS-ADRDA criteria were
      applied to diagnose Alzheimer's disease. RESULTS: Incidences of dementia and
      Alzheimer's disease were estimated at 16.3 and 11.4 per 1000 per year,
      respectively. Incidence estimates increased with age from 2 per 1000 in subjects
      aged 65-69 years to 74 per 1000 in subjects > 90 years. Incidence estimates of
      Alzheimer's disease showed the same increased from 0.7 per 1000 to 66 per 1000.
      Incidences of dementia and of Alzheimer's disease did not level off with age and
      were not different between genders.

PMID- 7721530
TI  - Pattern of drug use in a general population--prevalence and predicting factors:
      the Tromso study.
AB  - BACKGROUND: The aims of this study were to examine the prevalence of drug use,
      and how morbidity, use of health services, self-evaluated health, demographic
      pattern and lifestyle characteristics influence drug use in a general population.
      METHODS: The study was carried out in the municipality of Tromso, Norway. A
      sample of those aged 12-61 years was invited to the health survey, and 21,647
      (75%) participated. RESULTS: The proportion of drug users increased with age in
      both sexes (P < 0.0001); from 25% to 52% of women and from 18% to 38% of men.
      Drug use dependent mainly on chronic diseases (odds ratio [OR] = 2.5 [women], OR
      = 3.5 [men]) and physical distress, especially symptoms of pain (OR = 2.3
      [women], OR = 2.2 [men]). Number of visits to the doctor (OR = 2.4 [women], OR =
      3.2 [men]) and attitude to own health (OR = 1.9 [women], OR = 1.7 [men]) were
      also significant predictors for drug use. Mental distress, lifestyle and
      demographic factors were of marginal importance (OR < 1.3). Chronic diseases and
      visits to the doctor were the only predictors showing significant gender
      difference. CONCLUSIONS: Drug use increased with age and was twice as common in
      women as in men (OR = 2.0). After adjustment for differences in morbidity, visits
      to the doctor, and other factors the gender difference was significantly reduced
      (OR = 1.4). Higher drug use in women was attributed to women's higher level of
      physical distress (especially headache), higher numbers of visits to the doctor,
      and a higher proportion of reported chronic diseases (especially eczema,
      migraine) and depression compared with men.

PMID- 7721531
TI  - The determinants of excellent health: different from the determinants of ill
      health?
AB  - BACKGROUND: In the famous definition of the World Health Organization, health is
      'a state of complete physical, mental and social well-being, not merely the
      absence of disease or infirmity'. Until now, the distribution and determinants of
      the positive end of the health spectrum have not been studied extensively. In an
      exploratory analysis, we have compared the determinants of excellent health and
      of ill-health using data from a postal survey among 18,973 people in a region in
      the southeastern Netherlands. METHODS: Excellent health was defined as the
      presence of a very good self-assessment of health in the absence of any self
      reported chronic condition or health complaint, and was present in 8.2% of the
      survey population. Ill-health was defined as the presence of two or more self
      reported chronic conditions, four or more health complaints and a less-than-good
      self-assessment of health, and was present in 10.5% of the survey population. The
      remainder of the survey population was used as a reference group. Two sets of
      explanatory variables were available: a set of seven socio-demographic variables
      and a set of nine specific risk factors. Logistic regression analysis was used to
      assess the strengths and patterns of the associations between the determinants
      and the two outcome variables, excellent health and ill-health, controlling for
      age and gender. RESULTS: Both the socio-demographic variables and the specific
      risk factors had largely similar (but mirrored) patterns of association with
      excellent health and with ill-health. Important socio-demographic determinants of
      excellent health (and of ill-health) were education, employment status and
      urbanization (as well as age and gender). Important specific risk factors were
      leisure exercise, housing problems, smoking, negative life events, obesity and
      alcohol intake. The percentage of deviance accounted for by each of these sets of
      determinants was two to three times as large in the case of ill-health as in the
      case of excellent health. CONCLUSION: The processes by which excellent health is
      generated probably have much in common with those which generate ill-health. At
      the same time it is obvious that our understanding of the determinants of ill
      health is better than that of the determinants of excellent health, and further
      study of the latter is recommended.

PMID- 7721532
TI  - A computer simulation of household sampling schemes for health surveys in
      developing countries.
AB  - BACKGROUND: Cluster sample surveys of health and nutrition in rural areas of
      developing countries frequently utilize the EPI (Expanded Programme on
      Immunization) method of selecting households where complete enumeration and
      systematic or simple random sampling (SRS) is considered impractical. The first
      household is selected by choosing a random direction from the centre of the
      community, counting the houses along that route, and picking one at random.
      Subsequent households are chosen by visiting that house which is nearest to the
      preceding one. METHODS: Using a computer, and data from a survey of all children
      in 30 villages in Uganda, we simulated the selection of samples of size 7, 15 and
      30 children from each village using SRS, the EPI method, and four different
      modifications of the EPI method. RESULTS: The choice of sampling scheme for
      households had very little effect on the precision or bias of estimates of
      prevalence of malnutrition, or of recent morbidity, with EPI performing as well
      as SRS. However, the EPI scheme was inefficient and showed bias for variables
      relating to child care and for socioeconomic variables. Two of the modified EPI
      schemes (taking every fifth house and taking separate EPI samples in each quarter
      of the community) performed in general much better than EPI and almost as well as
      SRS. CONCLUSIONS: These results suggest that the unmodified EPI household
      sampling scheme may be adequate for rapid appraisal of morbidity prevalence or
      nutritional status of communities, but that it may not be appropriate for surveys
      which cover a wider range of topics such as health care, or seek to examine the
      association of health or nutrition with explanatory factors such as education and
      socioeconomic status. Other factors such as cost and the ability to monitor
      interviewers' performance should also be taken into account.

PMID- 7721534
TI  - Epidemiology of pertussis in Denmark: the impact of herd immunity.
AB  - BACKGROUND: An evaluation is presented of the Danish pertussis immunization
      programme, which consists of three injections of plain whole-cell pertussis
      vaccine given alone at ages 5 weeks, 9 weeks, and 10 months. DATA: The incidence
      of pertussis in vaccinated and unvaccinated children since the start of
      vaccination was obtained from the notification system for infectious diseases.
      Data for vaccination coverage were obtained from the National Social Security.
      The data for 1980-1986 were supplemented with data from culture-verified cases
      and hospitalized cases. RESULTS: Compared with other countries using four
      injections, incidence rates in Denmark are high, especially in pre-school years,
      leaving infants at a relatively high risk for contracting pertussis from
      siblings. However, compared with the era before general vaccination, the
      incidence of pertussis has fallen to one-sixteenth of its former levels. Today,
      only one in 20 vaccinated, and one in six unvaccinated children develop pertussis
      before the age of 15 years. This considerable fall, which has also occurred among
      unvaccinated children, is used to elucidate the importance of herd immunity,
      which, with the relatively high vaccination coverage in Denmark, was found to
      play a major role. CONCLUSIONS: The importance of herd immunity is stressed, and
      it is recommended that a fourth injection of pertussis vaccine is introduced to
      bring incidence rates down to the very low values found in countries with more
      intensive vaccination programmes.

PMID- 7721533
TI  - Epidemic cholera during refugee resettlement in Malawi.
AB  - BACKGROUND: In June 1988 a cholera epidemic occurred in a Mozambican refugee
      population resettling in southern Malawi. METHODS: A case-control study was
      conducted to determine possible risk factors for disease. The characteristics of
      48 refugee households with any member(s) hospitalized for suspected cholera were
      compared to 441 randomly sampled refugee households without hospitalizations.
      RESULTS: Vibrio cholerae 01 was isolated from 50% (5/10) of case-patient stool
      cultures. Having any water containers with > or = 10 T capacity was associated
      with a significantly lower odds of suspected cholera in households (adjusted odds
      ratio [aOR] = 0.02, 95% confidence interval [CI] : 0.003-0.12), as was having
      metal cooking pots (aOR = 0.3, 95% CI : 0.12-0.7), after adjusting for length of
      residence and socioeconomic status (logistic regression model). Households with
      two or more children < 5 years old were at markedly increased odds of suspected
      cholera (P < 0.0001). These results suggest that water containers and cooking
      pots served important preventive functions during this cholera outbreak. Young
      children may have contributed to cholera transmission, but the reason(s) remains
      undetermined.

PMID- 7721535
TI  - Models for prediction of the frequency of toxoplasmosis in pregnancy in
      situations of changing infection rates.
AB  - BACKGROUND: Estimation of the number of women infected during pregnancy with
      Toxoplasma gondii from seroconversion or seroprevalence data meets with various
      difficulties. Because of the high risk of transmission of the infection to the
      fetus such infections are however a major concern in pregnancy-related health
      planning. METHODS: The expected annual percentage of pregnant women infected with
      Toxoplasma was calculated using models with varying assumptions with regard to
      the infection rate, assumed to be independent of age but dependent on calendar
      time. Three situations were studied: a stable situation, a sudden fall in the
      infection rate and a gradually declining (slower or faster) infection rate over
      the lifetime of the pregnant women. RESULTS: With a constant infection rate, a
      maximum number of affected pregnancies occurs at a yearly infection rate of 4%.
      In countries with a strongly decreasing annual infection rate, estimates based on
      data on the relation between age and seropositivity related to only one period of
      time tend to overestimate the number of affected pregnancies by as much as 60%.
      CONCLUSIONS: In countries in transition from high to low infection rates, it is
      likely that the influence of decreasing immunity will, at least temporarily, more
      than outweigh the influence of the falling infection rates, resulting in a higher
      number of infected pregnant women. The models used can also describe situations
      with age-dependent variation in the infection rate, and may well apply to other
      infectious diseases relevant to pregnancy.

PMID- 7721536
TI  - Importance of smoking for Chlamydia pneumoniae seropositivity.
AB  - BACKGROUND: Population-based studies of the association between smoking and
      Chlamydia pneumoniae seropositivity do not exist. The role of smoking in the
      association between C. pneumoniae seropositivity and coronary artery disease
      (CAD) suggested by several studies has been debated. The aim of this study was to
      determine the relationship between smoking habits and C. pneumoniae IgG antibody
      titres in a middle-aged population. We also wanted to find out whether the
      difference in smoking habits between the sexes explains the higher C. pneumoniae
      antibody prevalence among men compared with women. RESULTS: After controlling for
      the effect of smoking, the risk of C. pneumoniae seropositivity remained 1.4
      times higher in men than in women. In men, the estimated risk for C. pneumoniae
      seropositivity (titre > or = 1:16) was significant only for smokers (adjusted
      odds ratio [OR] = 1.4). The adjusted OR for high seropositivity (titre > or =
      1:128) was 1.5 for smokers and 1.7 for ex-smokers. The risk for women was similar
      to that for men. CONCLUSIONS: The results provide evidence of an association
      between smoking and C. pneumoniae seropositivity in the general population. The
      higher prevalence of smoking in men does not explain the C. pneumoniae antibody
      prevalence in men compared with women.

PMID- 7721537
TI  - Limitations to the universal use of capture-recapture methods.

PMID- 7721538
TI  - Ecto-ATPases: identities and functions.
AB  - Ecto-ATPases are ubiquitous in eukaryotic cells. They hydrolyze extracellular
      nucleoside tri- and/or diphosphates, and, when isolated, they exhibit E-type
      ATPase activity, (that is, the activity is dependent on Ca2+ or Mg2+, and it is
      insensitive to specific inhibitors of P-type, F-type, and V-type ATPases; in
      addition, several nucleotide tri- and/or diphosphates are hydrolysed, but
      nucleoside monophosphates and nonnucleoside phosphates are not substrates). Ecto
      ATPases are glycoproteins; they do not form a phosphorylated intermediate during
      the catalytic cycle; they seem to have an extremely high turnover number; and
      they present specific experimental problems during solubilization and
      purification. The T-tubule Mg2+-ATPase belongs to this group of enzymes, which
      may serve at least two major roles: they terminate ATP/ADP-induced signal
      transduction and participate in adenosine recycling. Several other functions have
      been discussed and identity to certain cell adhesion molecules and the bile acid
      transport protein was suggested on the basis of cDNA clone isolation and
      immunological work.

PMID- 7721539
TI  - Molecular genetic approaches to the study of human craniofacial dysmorphologies.
AB  - Craniofacial dysmorphologies are common, ranging from simple facial disfigurement
      to complex malformations involving the whole head. With the advent of gene
      mapping and cloning techniques, the genetic element of both simple and complex
      human craniofacial dysmorphologies can be investigated. For many of the
      dysmorphic syndromes, it is possible to find families that display a particular
      phenotype in either an autosomal dominant, recessive, or X-linked manner. This
      article focuses on a subgroup of craniofacial dysmorphologies, covering these
      three main inheritance patterns, that are being studied using molecular biology
      techniques: DiGeorge syndrome, Treacher Collins syndrome, Greig
      cephalopolysyndactyly syndrome, acrocallosal syndrome, amelogenesis imperfecta,
      and X-linked cleft palate with ankyloglossia. Once the mutated or deleted gene or
      genes for each syndrome have been cloned, patterns of normal and abnormal
      craniofacial development should be elucidated. This should enhance both diagnosis
      and treatment of these common and disfiguring disorders.

PMID- 7721540
TI  - Effects of electromagnetic fields on molecules and cells.
AB  - Evidence suggests that cell processes can be influenced by weak electromagnetic
      fields (EMFs). EMFs appear to represent a global interference or stress to which
      a cell can adapt without catastrophic consequences. There may be exceptions to
      this observation, however, such as the putative role of EMFs as promoters in the
      presence of a primary tumor initiator. The nature of the response suggests that
      the cell is viewing EMFs as it would another subtle environmental change. The age
      and state of the cell can profoundly affect the EMF bioresponse. There is no
      evidence that direct posttranscription effects occur as a result of EMF exposure.
      Although transcription alterations occur, no apparent disruption in routine
      physiological processes such as growth and division is immediately evident. What
      is usually observed is a transient perturbation followed by an adjustment by the
      normal homeostatic machinery of the cells. DNA does not appear to be
      significantly altered by EMF. If EMF exposure is associated with an increased
      risk of cancer, the paucity of genotoxic effects would support the suggestion
      that the fields act in tumor promotion rather than initiation. The site(s) and
      mechanisms of interaction remain to be elaborated. Although there are numerous
      studies and hypotheses that suggest the membrane represents the primary site of
      interaction, there are also several different studies showing that in vitro
      systems, including cell-free systems, are responsive to EMFs. The debate about
      potential hazards or therapeutic value of weak electromagnetic fields will
      continue until the mechanism of interaction has been clarified.

PMID- 7721541
TI  - Effects of vasoconstrictors on rabbit coronary arteries exposed to iohexol with
      addition of electrolytes (sodium and calcium).
AB  - RATIONAL AND OBJECTIVES: A well-known side effect of contrast media (CM) is
      vasodilation. Different types of CM in vitro inhibit the action of
      vasoconstrictors to various degrees. The nonionic CM iohexol inhibits the action
      less than ionic CM. In this study, the authors investigate whether the addition
      of electrolytes to iohexol causes less inhibition of the vasoconstrictors.
      Vasoconstriction dependent on potential-operated calcium channels (POCs)
      (potassium chloride), or receptor-operated calcium channels (ROCs) (histamine,
      endothelin-1, and prostaglandin F2 [PGF2 alpha]) was specifically studied.
      METHODS: Segments of rabbit coronary arteries were mounted between two L-shaped
      prongs in tissue baths with buffer solution or solutions of iohexol (140 mg I/mL)
      with addition of different concentrations of NaCl and CaCl2. The responses of the
      vessels to increasing concentrations of a vasoconstrictor were examined.
      Concentration of vasoconstrictor versus contractile response curves were plotted,
      and the maximal contraction of the vasoconstrictor (Emax) and half maximal
      constriction were calculated. RESULTS: Addition of 30 mM NaCl and 1.5 mM CaCl2
      caused a vasoconstriction to KCl in iohexol almost identical to its
      vasoconstriction in buffer. Higher concentrations of NaCl caused decreasing Emax
      of all vasoconstrictors. The inhibition of the ROC-dependent vasoconstrictors
      could not be normalized by the addition of electrolytes. CONCLUSIONS: The
      inhibition of the POC-dependent vasoconstrictor was caused by "ion toxicity" of
      iohexol. The inhibition of the ROC-dependent vasoconstrictors was caused by other
      mechanisms, in a manner compatible with a blocking effect on ROCs.

PMID- 7721542
TI  - Optimization of chest films of equalization radiography (advanced multiple beam
      equalization radiography). Comparison by means of a receiver operating
      characteristic study of simulated nodular interstitial disease.
AB  - RATIONALE AND OBJECTIVE: To optimize screen-film combinations for equalization
      radiography (advanced multiple beam equalization radiography [AMBER]), five
      different film-screen-technique combinations were compared by receiver operating
      characteristics study of simulated interstitial disease. MATERIALS AND METHODS:
      The Ortho C-Lanex Regular and the Insight Thoracic Imaging HC system were
      compared in conventional nonequalized technique; T-Mat G-Lanex Regular and T-Max
      L-Lanex Regular were compared in conventional, nonequalized, and AMBER technique;
      and an experimental high-contrast, low-noise, near-zero crossover film-screen
      combination was compared in AMBER technique. Interstitial disease was simulated
      by superimposing birdseed on the back of a humanoid phantom. Twenty-five
      posterior-anterior radiographs were made with each technique. Seven observers
      scored the presence of interstitial disease in each of the quadrants on a 5-point
      scale following receiver operating characteristic methodology. RESULTS: The
      highest performance was found with the experimental film-screen-AMBER combination
      (Az = 0.92) and the lowest with the T-Mat L-Lanex Regular-AMBER combination (Az =
      0.83) and the Insight Thoracic Imaging HC system-conventional combination (Az =
      0.85). T-Mat L-Lanex Regular-conventional ranked second (Az = 0.90) while T-Mat G
      Lanex Regular-conventional (Az = 0.89), T-Mat L-Lanex Regular-AMBER (Az = 0.88)
      and Ortho-C-Lanex Regular-conventional (Az = 0.87) scored lower. CONCLUSION:
      Higher contrast films in AMBER improve diagnostic performance, whereas a loss of
      information is found if the AMBER system is combined with lower contrast films.

PMID- 7721543
TI  - Effects of two low-osmolar contrast media, ioxaglate and iopamidol, on
      erythrocyte membrane elasticity.
AB  - RATIONALE AND OBJECTIVES: The effect of ioxaglate and iopamidol, two recently
      developed low-osmolality contrast media, on the shear elasticity of erythrocyte
      membranes was studied at an iodine concentration of 300 mg/mL and at a 20% volume
      concentration and compared with that obtained for control solutions matched in
      osmolality. METHODS: The authors used a micromanipulation technique, which
      consists of visualizing deformations of individual erythrocytes when gently
      aspirated into the tip of a glass micropipette by an accurately controlled
      pressure. An erythrocyte membrane shear elasticity modulus mu was then deduced.
      An increase in mu corresponded to an increase in erythrocyte membrane rigidity.
      RESULTS: In all cases, the erythrocytes remained discocytic. The shear elasticity
      modulus of the erythrocyte membrane is found to be (1) in the presence of
      ioxaglate (4.3 +/- 0.9 microN/m) lower (P < .001) than in the presence of
      hyperosmolar saline (6.2 +/- 1.3 microN/m) and lower (P < .02) than in the
      presence of iso-osmolar control (4.7 +/- 0.7 microN/m); (2) in the presence of
      iopamidol (5.4 +/- 0.7 microN/m) lower (P < .001) than in the presence of
      hyperosmolar sucrose (6.4 +/- 1.2 microN/m) and higher (P < .001) than in the
      presence of iso-osmolar control (4.7 +/- 0.7 microN/m); and (3) lower (P < .001)
      in the presence of ioxaglate (4.3 +/- 0.9 microN/m) than in the presence of
      iopamidol (5.4 +/- 0.7 microN/m). CONCLUSIONS: Under the experimental conditions
      used, both contrast media (ioxaglate and iopamidol) modify the erythrocyte
      membrane shear elasticity modulus less than do the matched hyperosmolar controls.
      Moreover, ioxaglate makes the erythrocyte membrane less rigid, and iopamidol
      makes the erythrocyte membrane more rigid than does the iso-osmolar control.

PMID- 7721544
TI  - Spiral computed tomography arterial portography with three-dimensional volumetric
      rendering for oncologic surgery planning. A retrospective analysis.
AB  - RATIONALE AND OBJECTIVES: Surgical resection of metastatic neoplasms of the liver
      can prolong survival of patients. The decision to resect a tumor depends to a
      great extent on the location of lesions relative to hepatic vasculature. Spiral
      computed tomography arterial portography (SCTAP) is an excellent technique for
      preoperative localization of tumors. The addition of three-dimensional rendering
      of image data sets should enhance the efficiency and accuracy of the
      interpretation of these data by the surgeon. METHODS: Fourteen patients with
      surgically and pathologically proven solitary and multiple metastatic hepatic
      neoplasms underwent SCTAP: Volume data sets thus derived were used to produce
      life-like three-dimensional animated images through a process known as volumetric
      rendering. These images were presented to the surgeon, who evaluated them based
      on several criteria. RESULTS: Accurate and clinically useful images were produced
      routinely in 13 of 14 patients. CONCLUSIONS: Clinical utility of three
      dimensional rendering of SCTAP data sets for preoperative localization of hepatic
      lesions has been shown retrospectively. A larger, prospective study is suggested
      to demonstrate the accuracy and efficacy of the technique.

PMID- 7721545
TI  - Evaluation of myocardial motion tracking with cine-phase contrast magnetic
      resonance imaging.
AB  - RATIONALE AND OBJECTIVES: The accuracy of myocardial motion measurements,
      computed from cine-phase contrast (cine-PC) magnetic resonance (MR) velocity
      data, was compared with directly visualized motion of MR signal voids caused by
      implanted tantalum markers in anesthetized dogs. METHODS: Magnetic resonance
      imaging (MRI) data were electrocardiogram-gated and divided into 16 phases per
      cardiac cycle. Myocardial trajectories as a function of time in the cardiac cycle
      were measured using both methods for four to seven markers in each of eight
      animals. RESULTS: The peak observed in-plane excursion was 4.0 +/- 2.1 mm. The
      average deviation between displacements derived from velocity data versus
      displacements visualized directly was 1.1 +/- 0.7 mm (27.5% of the peak
      displacement). The difference was less if three separate MR scans were used to
      measure each velocity component in the cine-PC method. This improvement is
      probably caused by improved temporal resolution. CONCLUSIONS: Cine-PC MRI offers
      a noninvasive method for accurate quantification of myocardial motion.

PMID- 7721546
TI  - Magnetic resonance imaging of an experimental model of intracranial metastatic
      disease. A study of lesion detectability.
AB  - RATIONALE AND OBJECTIVES: The detectability of brain metastases was evaluated in
      a rabbit model, with attention to magnetic resonance contrast dose and timing of
      image acquisition after injection of contrast medium. METHODS: Five New Zealand
      white rabbits were studied at 1.5 T 6 to 7 days and 11 to 12 days after surgical
      implantation of an adenocarcinoma tumor nidus. T1- and T2-weighted spin-echo
      images (0.9 x 0.9 x 2 mm3 voxel size) were obtained before administration of
      contrast medium. T1-weighted images were repeated 5, 15, and 30 minutes after
      intravenous injection of 0.1 mmol/kg gadoteridol. At 40 minutes, a supplemental
      dose of 0.2 mmol/kg (0.3 mmol/kg cumulative dose) was administered, with T1
      weighted images repeated at 5, 15, and 30 minutes after the second injection.
      RESULTS: Six to 7 days after tumor implantation, lesion enhancement (percent
      change, with normalization to baseline and equilibrium values) was 42 +/- 9% at 5
      minutes, 48 +/- 9% at 15 minutes, and 42 +/- 10% at 30 minutes after
      administration of 0.1 mmol/kg gadoteridol. After administration of 0.3 mmol/kg
      gadoteridol, lesion enhancement was 111 +/- 13% at 5 minutes, 116 +/- 8% at 15
      minutes, and 100% at 30 minutes. On film review, 2 of 5 lesions were not
      detectable at 6 to 7 days after tumor implantation with 0.1 mmol/kg gadoteridol.
      Administration of 0.3 mmol/kg gadoteridol provided for lesion identification in
      each instance. Eleven to 12 days after tumor implantation, one lesion was not
      detectable with 0.1 mmol/kg gadoteridol. Administration of 0.3 mmol/kg
      gadoteridol again provided for lesion identification in all cases. Mean lesion
      enhancement increased from 39 +/- 15% to 104 +/- 10%. CONCLUSIONS: The
      administration of 0.3 mmol/kg gadoteridol (high dose) compared with 0.1 mmol/kg
      gadoteridol (conventional dose) improves metastatic lesion detectability in the
      brain. The lesions identified only at high dose were confirmed by histopathology.
      Smaller lesions were not detected at a dose of 0.1 mmol/kg.

PMID- 7721547
TI  - Whole body quantitative autoradiographic study of the biodistribution of
      iobitridol in rats.
AB  - RATIONALE AND OBJECTIVES: Iobitridol is a new nonionic low-osmolality contrast
      medium. During preclinical development of this agent, it was of interest to
      verify that it behaves like other urographic and angiographic contrast agents
      (i.e., as a tracer of extracellular fluid). METHODS: Male and female rats were
      imaged using a quantitative autoradiographic method after intravenous
      administration of iodine-125-labeled product at a dose of 300 mg iodine/kg.
      RESULTS: The radioactivity was rapidly distributed with substantial uptake in the
      thyroid, kidneys, and skin after 10 minutes. The central nervous system showed no
      uptake. The radioactivity was rapidly eliminated (i.e., after 24 and 48 hours,
      only traces were found) except in the thyroid (because of free radiolabeled
      iodides present in small quantities in the administered solution). The
      considerable renal uptake after administration can be attributed to urinary
      excretion of the radioactivity (86% of the administered dose after 24 hours).
      Total elimination was achieved after 48 hours. No sex-related effects were
      observed. CONCLUSION: The absence of a target organ, the abundant and rapid
      urinary elimination, and the absence of transfer across the blood-brain barrier
      suggest that iobitridol is a tracer of extracellular fluid.

PMID- 7721548
TI  - New approaches to motor unit potential analysis.
AB  - The current state of motor unit potential (MUP) analysis is reviewed. New
      quantitative analysis methods are described and compared with traditional manual
      measurements. The emphasis in this review is on a new method, multi-MUP analysis
      and the detection of individual outliers. Multi-MUP analysis is based on
      decomposition EMG. The main advantage of these new methods is that they save time
      and allow immediate comparison between obtained results and reference values. The
      results are repeatable and independent of the investigator.

PMID- 7721549
TI  - Infantile spasms combined with partial seizures: electroclinical study of eleven
      cases.
AB  - We studied 11 infants (7 males) with combined infantile spasms (IS) and partial
      seizures. The age of onset of the spasms ranged from 6 days to 9 months. All of
      the children had neurological or CT/MRI abnormalities, and five also had a family
      history of epilepsy. The clinical and polygraphic patterns of the clusters of
      spasms combined with partial seizures were analysed. Ten infants were followed-up
      for a mean period of 3 years, 4 months (range 1 year 10 months to 4 years 11
      months). At the last check-up, the seizures were controlled in 2 patients; the
      others continued to have spasms and/or partial seizures. All of the patients
      developed mild to severe psychomotor retardation. This condition defines a
      subgroup of infants presenting with IS, which is distinct from West syndrome.

PMID- 7721551
TI  - Cognitive impairment and quality of life in long-term survivors of malignant
      brain tumors.
AB  - Thirtysix long-term survivors following the treatment of a malignant
      supratentorial brain tumor were examined for cognitive functions and global level
      of autonomy. Eighteen patients were symptom-free (SF) and 18 had clinical and
      neuroradiological recurrence (RE). The control group included 30 healthy
      subjects. All subjects underwent a neuropsychological battery for general and
      specific cognitive functions. The level of autonomy was assessed by means of the
      Karnofsky Performance Scale (KPS) for oncological patients. SF patients showed
      less impairment than RE patients both at the tests, as well as on the KPS. The
      cognitive deficits were subclinical in most SF patients, the tests for attention,
      memory and word fluency being the most sensitive in detecting subtle
      dysfunctions. The association between tumor location and specific cognitive
      deficits was inconstant in both patient groups. The results suggest that even
      subtle cognitive deficits can prevent SF long-term survivors from returning to
      premorbid autonomy and occupations, and that neuropsychological tests may be used
      as complementary routine indicators of their quality of life. Furthermore, our
      data show that, in selected patients, combined treatments and therapeutic
      insistence do not necessarily have the same deleterious effects.

PMID- 7721550
TI  - Mutation in the S4 segment of the adult skeletal sodium channel gene in an
      Italian paramyotonia congenita (PC) family.
AB  - The periodic paralyses are a group of autosomal dominant muscle diseases sharing
      the common feature of episodic stiffness and weakness, usually occurring with
      muscle cooling (as in the case of paramyotonia congenita, PC phenotype) or
      changes in extracellular K+ levels resulting from various precipitating factors
      (hyperkalemic periodic paralysis, HYPP and hypokalemic periodic paralysis,
      HypoPP). It is now known that HYPP maps to chromosome 17q, and that PC and a form
      of myotonia congenita without periodic paralysis also map to the 17q locus, thus
      indicating that they derive from allelic variants. So far, these disorders have
      been described in various ethnic groups but, to our knowledge, have never been
      reported in Italy. We describe a mutation in an S4 segment of the adult skeletal
      muscle sodium channel in a clinically-defined Italian family that leads to the
      paramyotonia congenita (PC) phenotype with dominant autosomal inheritance and
      temperature-related symptoms (regional weakness following cooling and exercise),
      present since childhood in all of the affected family members.

PMID- 7721552
TI  - Cortical output modulation after rapid repetitive movements.
AB  - Transcranial magnetic stimulation was used to evaluate changes in motor cortex
      excitability after rapid repetitive movements in five healthy subjects aged 23-30
      years, by considering the amplitude of motor evoked potentials (MEPs) at rest and
      after one minute of maximal frequency repetitive abduction-adduction movements of
      the thumb. In addition, M and F waves were evaluated by stimulating the median
      nerve at the wrist. All of the examined subjects showed a clear modification in
      post-exercise MEP amplitudes, with a mean maximal reduction of 50-60% in
      comparison with basal values and complete recovery after a period of about 35
      minutes. The time course of this phenomenon showed a triphasic pattern: (I) a
      rapid decrease phase up to the fifth minute; (II) a maximal depression phase for
      a period of about ten minutes; (III) a slow return to basal values. No
      significant changes were observed in post-exercise M and F waves. These results
      show the existence of a reversible modulation of the excitability of the upper
      motor neuron after rapid repetitive movements. It is likely that this modulation
      takes place at the level of the motor cortex and that its anatomo-functional
      substrate is represented by the activation of inhibitory intracortical circuits.

PMID- 7721553
TI  - Long latency evoked potentials in a case of corpus callosum agenesia.
AB  - Following monoaural stimulation, long latency auditory evoked potentials (LLAEPs)
      recorded from contralateral temporal areas have a shorter latency and larger
      amplitude than those recorded from the ipsilateral temporal areas. This
      observation agrees with the operational model drawn up in 1967 by Kimura, which
      assumes that only anatomically prevailing crossed auditory pathways are active
      during dichotic hearing, while direct pathways are inhibited. The inputs may then
      be conveyed to the contralateral cortex, from where they finally reach the
      ipsilateral temporal areas by means of interhemispheric commissures. It is this
      mechanism which may underline the right ear advantage for verbal stimuli and the
      left ear advantage for melodies observed when administering dichotic listening
      tasks. With the aim of verifying this hypothesis, we recorded temporal LLAEPs in
      a 21 year-old woman suffering from complex partial seizures, whose CT scan and
      MRI showed corpus callosum agenesia. Our data support the hypothesis that
      ipsilateral pathways are greatly inhibited by the contralateral pathways, and
      therefore auditory stimuli can be supposed to reach the contralateral auditory
      cortex from where they are transferred through the corpus callosum to the
      ipsilateral auditory cortex.

PMID- 7721554
TI  - Deep cerebral venous thrombosis and hereditary tissue plasminogen activator (t
      PA) deficiency.
AB  - We describe a patient with defective tissue plasminogen activator (t-PA) release
      who developed internal cerebral vein thrombosis. She recovered completely and, as
      shown by MRI, favourable outcome was probably related to vascular recanalisation.
      Other members of the pedigree had a similar fibrinolytic deficiency without
      clinical manifestations. The use of oral contraceptives may have contributed to
      the patient's hypercoagulable state.

PMID- 7721555
TI  - The relativity of biocompatibility. A critique of the concept of
      biocompatibility.
AB  - The concept of biocompatibility of the materials used in surgical reconstruction
      of joints, ligaments, and tendons is controversial, as evinced by the conflicting
      definitions proposed by the many authors who have studied the host reaction to
      the presence of implants and their breakdown products. We propose that
      biocompatibility of contemporary medical implants is not a property of the
      chemical composition of the biomaterials but depends rather on their physical
      attributes. The histological reaction patterns of tissue to the presence of
      polyethylene in diverse physical states are described. The inflammatory response
      evoked by the implants is laudable in so far as it precedes and accompanies the
      adequate tissular incorporation of the devices used. On the other hand, the
      granulomatous reaction induced by small, irregularly shaped and edgy breakdown
      products adversely affects the life span of the implants. Thus the manner in
      which the host handles the biomaterials is determined primarily by the physical
      state of the biomaterials (rather than their chemical composition), which in turn
      determines the success or failure of reconstructive surgery. It logically follows
      that biocompatibility constitutes a relativistic concept.

PMID- 7721556
TI  - Balneotherapy for rheumatoid arthritis at the Dead Sea.
AB  - Thirty-six patients with active rheumatoid arthritis were treated for 12 days at
      the Ein Gedi Spa. The patients were allocated randomly to four study groups.
      Group 1 (n = 9) was treated with daily baths in the Dead Sea, group 2 (n = 9) was
      treated with daily sulphur baths, group 3 (n = 10) was treated with a combination
      of daily Dead Sea bathing and sulphur baths, and group 4 (n = 8) served as a
      control group. All patients were assessed by a rheumatologist who was blinded to
      the treatment modalities and group allocation. Clinical parameters assessed
      included: duration of morning stiffness, 15 m walk time, grip strength,
      activities of daily living, patient's assessment of disease severity, number of
      active joints, and the Ritchie articular index. Statistically significant
      improvement lasting up to 3 months was observed only in the three treatment
      groups.

PMID- 7721557
TI  - Calcium channel blocker decreases pentagastrin-stimulated alkaline-tide: a role
      for extracellular calcium in gastric acid secretion.
AB  - We previously showed that repeated stimulation of the gastrin receptor may lead
      to down-regulation. We hypothesized that entry of extracellular Ca2+ may
      replenish cytosolic Ca2+ and enable continuation of the acid-secretion process.
      Pentagastrin-stimulated alkaline-tide study was performed in seven duodenal ulcer
      patients on 2 separate days--with and without pretreatment with verapamil (Ca2+
      channel blocker). The alkaline-tide test may substitute the conventional gastric
      acid collection as previously described. A significant rise in base excess after
      pentagastrin injection was found on the first day of the study, from 0.400 +/-
      1.233 to 2.230 +/- 1.330 (mean +/- SD, P = 0.02). On the second day the rise was
      not statistically significant, from -0.200 +/- 0.838 to 0.440 +/- 1.200 (mean +/-
      SD, P = 0.27). In 6 of the 7 patients the alkaline-tide decreased from 45.29 +/-
      21.75 mEq/45 min on the first day to 21.56 +/- 17.48 mEq/45 min on the second day
      of the study (mean +/- SD, P = 0.029), a decrease of 63.6 +/- 36.2%. Our findings
      may support a dual source for Ca2+, the second messenger in gastrin-dependent
      gastric acid secretion. The first increase of intracellular Ca2+ comes from
      cellular stores, and the second from extracellular source by Ca2+ channels, which
      can be blocked by verapamil.

PMID- 7721558
TI  - The diagnostic reliability of anti-endomysial antibody in celiac disease: the
      north Israel experience.
AB  - Assessment of anti-endomysial antibody (EMA) for the diagnosis and follow-up of
      celiac disease (CD) is widely accepted, but its applicability has never been
      investigated in Israel. We therefore investigated EMA as a diagnostic tool in a
      pediatric population, residing in the northern part of Israel, with suspected
      celiac disease. EMA was assessed by an indirect immunofluorescence assay using
      monkey esophageal sections as a substrate in 22 active CD, 17 non-active CD, and
      22 non-CD children. EMA titers were correlated with small bowel mucosal
      pathology. Sensitivity and specificity of EMA were 100%. EMA levels are diet
      dependent, increasing on a gluten-containing diet and decreasing with gluten
      withdrawal after 3-12 months. EMA is a reliable marker for the diagnosis of CD,
      and reflects gluten intake changes and patients' dietary compliance. In our
      laboratory, EMA is suitable for the diagnosis and follow-up of CD.

PMID- 7721559
TI  - High prevalence of vitamin D deficiency among Ethiopian women immigrants to
      Israel: exacerbation during pregnancy and lactation.
AB  - A population of 125 adult Ethiopian women immigrants to Israel was screened for
      serum levels of calcium, phosphorus, and alkaline phosphatase. Five women
      (prevalence of 4%) had hypocalcemia and in one of them osteomalacia was found. In
      the other 120 subjects normal values were recorded. All five patients had low
      serum levels of 25 hydroxy (OH) vitamin D3 and high parathyroid hormone (PTH)
      levels. In four of the five patients, clinical and biochemical manifestations of
      vitamin D deficiency were detected during pregnancy or lactation. Treatment with
      vitamin D2 for 4-13 months resulted in clinical improvement and partially
      corrected the biochemical abnormalities, but low serum vitamin D levels and
      elevated PTH levels persisted. We conclude that vitamin D deficiency among female
      Ethiopian immigrants to Israel can be ascribed either to dark skin or low calcium
      and vitamin D intake, or both. As far as we known this is the first report of
      vitamin D deficiency among such immigrants. Our study suggests the need to be
      alert to the possibility of vitamin D deficiency in Ethiopian women who have
      immigrated to Israel, in particular those who are pregnant or are breast-feeding.

PMID- 7721560
TI  - MELAS syndrome: peripheral neuropathy and cytochrome C-oxidase deficiency: a case
      report and review of the literature.
AB  - A 4-year-old boy presented with developmental delay, aggressive behavior, and
      incoordination. His EEG showed a diffuse encephalopathy. At age 10 he developed
      convulsions and severe migraine-like headaches. Muscle wasting, arreflexia, and
      lactic acidemia following exercise were noted. Electromyography was myopathic and
      nerve conduction studies revealed a peripheral neuropathy. Muscle biopsy
      demonstrated variation in fiber size and an excess of lipid droplets. He than had
      several stroke-like episodes and periods of unconsciousness, associated with
      severe metabolic acidosis. Muscle cytochrome C oxidase was abnormally low. This
      boy displayed the classical clinical and biochemical features of MELAS syndrome,
      namely Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like
      episodes. Treatment included carnitine, vitamin C, vitamin K, riboflavin,
      coenzyme Q10, and corticosteroids. He died at the age of 14 years following an
      episode of seizures, coma, and gastrointestinal hemorrhage. This is the first
      reported case of MELAS syndrome in Israel.

PMID- 7721561
TI  - A study of 609 infertile couples: a comparison of Jewish and Arab patients.

PMID- 7721562
TI  - Management of uterine perforation complicating first-trimester termination of
      pregnancy.

PMID- 7721563
TI  - Cholesterol granuloma of the tunica vaginalis mimicking a neoplasm.

PMID- 7721564
TI  - Vitamin D levels in dark-skinned people.

PMID- 7721565
TI  - Epidemiological study of 609 infertile couples.

PMID- 7721566
TI  - Oxidative modification of low density lipoprotein and its relation to
      atherosclerosis.

PMID- 7721567
TI  - Use of ECFMG certifying examinations for national comparisons: performance of
      graduates of Israeli medical schools in basic and clinical science examinations.
AB  - Examinations were used for comparison of Israeli medical school graduates. The
      two schools with traditional curricula had higher pass rates for first takers of
      Day 1 (68% and 61%, mean scores 76.6 and 76.4) than the community-based school
      (44%, mean score 74.5) and the technologically oriented school (40%, mean score
      72.5). There were similar pass rates for traditional school first takers of Day 2
      (97% and 91%, mean scores 82.4 and 80.4) as for community-based school first
      takers (94%, mean score 80.1). The traditional schools and the community-based
      school demonstrated higher pass rates and mean scores for first takers of Day 2
      than the technologically oriented school. Analysis of the time lapse between the
      basic science curriculum and taking the basic science examination reveals no
      trend in scores or pass rates. While the likelihood of better performance on Day
      1 seems enhanced by traditional curricula, there is an equivalent performance on
      Day 2 by graduates of schools with traditional curricula.

PMID- 7721568
TI  - Gems from the Talmud: Public Health I--Water supply.

PMID- 7721569
TI  - Selman Abraham Waksman--pioneer in antibiotics.

PMID- 7721570
TI  - Diagnostic criteria for screening headache patients for temporomandibular
      disorders.
AB  - Patients with temporomandibular disorders frequently suffer from headache. The
      purpose of this study was to develop a simple screening exam which would allow
      the physician to identify headache patients with coexisting temporomandibular
      disorders. Twenty-eight migraine and 27 tension headache patients were identified
      by a board certified neurologist and then were examined by a dentist for signs of
      temporomandibular disorders. These patients were then compared to 63 patients
      with temporomandibular internal derangements and 62 patients with myofascial pain
      dysfunction. Comparisons of the clinical signs showed that the temporomandibular
      internal derangement and myofascial pain dysfunction patients differed
      significantly from the headache patients in regards to specific signs of jaw
      dysfunction. The presence of reciprocal clicking of the temporomandibular joint
      or pain with maximum jaw opening and pain upon palpation of the temporomandibular
      joint distinguished temporomandibular internal derangement patients from headache
      patients. These criteria have a sensitivity of 92% and specificity of 91%. Pain
      on palpation over the temporomandibular joint, or pain with maximum jaw opening
      using passive stretch, and pain with lateral movement of the jaw, distinguished
      myofascial pain dysfunction patients from headache patients. These criteria have
      a sensitivity of 77% and specificity of 85%. By using these screening tests, the
      physician can identify the concurrent existence of temporomandibular disorders in
      headache patients and triage the patient to a clinician knowledgeable in the
      diagnosis and treatment of temporomandibular disorders for further evaluation.

PMID- 7721571
TI  - Headache characteristics in hospitalized patients with Lyme disease.
AB  - We reviewed 49 patients consecutively hospitalized for neurologic Lyme disease to
      determine the frequency and characteristics of recent onset headaches in this
      group. All patients had positive serum Lyme ELISAs and other neurologic illness
      excluded. Recent-onset headache occurred in 26 of 49 patients (53%). Patients
      with headaches more commonly had central nervous system involvement (54% vs 19%,
      P < .05) and flu-like illness (58% vs 19%, P < .0005). Eight of 26 (31%) met
      criteria for meningitis or encephalitis with abnormal CSF examinations. All 8 had
      focal findings (6), cognitive dysfunction (1), or both (1). The remaining 18
      patients had recent-onset headaches resembling migraine (9), tension-type
      headache (5), or neither (4). Antibiotic treatment resulted in complete headache
      resolution in 11 of 14 patients with available follow-up data. Based on these
      findings, we conclude that recent-onset headaches are common in patients
      hospitalized with Lyme disease. Of those with meningitis or encephalitis
      requiring intravenous antibiotics, all had focal neurologic findings or cognitive
      abnormalities, not just headaches.

PMID- 7721572
TI  - Quantification of headache disability: a diagnostic-based approach.
AB  - The quantification of the social and economic handicaps caused by headache is a
      complex problem, especially given the great variability of headache patients'
      clinical pictures. In the present study, 400 patients, consecutively admitted to
      Headache Centers in Pavia and Milan, were interviewed on the relationship between
      headache and their work and social activities, in order to evaluate their
      socioeconomic handicap due to headache. The analysis of the data primarily
      focused on attack-type headaches (migraine, cluster headache, and episodic
      tension-type headache) and chronic or daily headaches (chronic tension-type
      headache and migraine combined with tension-type headache). These latter types
      were often characterized by the daily use or abuse of analgesics. The overall
      profile which emerged from the study reveals relatively low levels of handicap or
      disability in work and social activities. These low levels can be mainly
      attributed to timely, and at times excessive, use of analgesics.

PMID- 7721573
TI  - SUNCT syndrome: trials of drugs and anesthetic blockades.
AB  - Nine patients with the SUNCT syndrome (Spanish and Norwegian patients) have, over
      many years, been given several drugs effective in the cluster headache syndrome,
      trigeminal neuralgia, and other headaches, as well as drugs not previously used
      in headache. Various cranial nerves were also anesthetized in an endeavor to
      ameliorate the suffering of those patients. Although a partial effect was
      obtained with carbamazepine and corticosteroids in some patients, none of the
      drugs or anesthetic blockades had consistent, lasting, complete effect on
      headache paroxysms in SUNCT. The essentially negative outcome of this study aids
      in further characterizing SUNCT as a separate disorder, and, above all, in
      distinguishing it from trigeminal neuralgia and the cluster headache syndrome.

PMID- 7721574
TI  - SUNCT syndrome: cerebral SPECT images during attacks.
AB  - Two patients with SUNCT syndrome (short-lasting, unilateral, neuralgiform
      headache attacks with conjunctival injection and tearing) were investigated.
      Blood flow velocity in the middle cerebral artery was monitored before, during,
      and outside four spontaneous attacks. An interhemispheric asymmetry was observed.
      In the second case, velocity decreased significantly on both sides during attacks
      in comparison with preattack values. Cerebral SPECT (single photon emission
      computed tomography) images were obtained during a bout and between attacks in
      one patient. The radiocompound was injected 5 to 10 seconds after the start of an
      attack. In both patients, normal tracer uptake and symmetric perfusion was
      observed during headache periods.

PMID- 7721575
TI  - Applicability of the 1988 IHS criteria to headache patients under the age of 18
      years attending 21 Italian headache clinics. Juvenile Headache Collaborative
      Study Group.
AB  - Seven hundred nineteen young patients attending 21 Italian headache care settings
      were evaluated by a diagnostic headache interview and a neurological examination.
      Headache disorders were classified according to the current 1988 criteria of the
      International Headache Society (IHS); 54.9% of the patients suffered from
      migraine, 33.9% from tension-type headache, 1.9% from secondary headache, and
      3.4% had non-classifiable headache. A further 5.9% of the patients were not
      classified due to incomplete questionnaires. Of the 395 patients with migraine,
      44.5% were affected by migraine without aura, 29.9% by migraine with aura, 1.3%
      from other migraine forms, and 24.3% by migrainous disorders which do not fulfill
      the 1988 IHS diagnostic criteria for headache. Among the 244 patients with
      tension-type headache, 51.6% had episodic tension-type headache, 15.2% chronic
      tension-type headache, and 33.2% headache of the tension-type which does not
      fulfill the 1988 IHS criteria for episodic and chronic tension-type headache. In
      young migraine patients, pain was of a pulsating type in 55.7%, severe in 57.8%,
      unilateral in 42.6%, and aggravated by routine physical activity in 38.9%.
      Tension-type headache was described as pressing in 73.8%, mild or moderate in
      75.7%, bilateral in 87.4%, and not aggravated by routine physical activity in
      85.5%. The duration of pain was less than 2 hours in 35% of the cases in migraine
      sufferers and less than 30 minutes in 26.7% of tension-type headache sufferers.
      Nausea, phonophobia, and photophobia were present in at least half of the
      migraine patients and in one third of tension-type headache patients,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721576
TI  - The frontotemporal region plays a role in the genesis of migraine without aura.
AB  - We have compared the migraine-inducing effect of nitroglycerin ointment applied
      to the frontotemporal region of the head, which is innervated by the ophthalmic
      and maxillary divisions of the trigeminal nerve, with that of nitroglycerin
      applied to the chin (innervated by the mandibular division), the posterolateral
      region of the neck (innervated by the second and third cervical roots), the
      lateral surface of the proximal third of the forearm (innervated by the sixth
      cervical root), and the medial surface of the upper-arm region (second dorsal
      root). One hundred patients suffering from migraine without aura were randomly
      divided into five equal groups. Each group received an application of 5 mg
      nitroglycerin in 2% ointment on a preselected body area for 2 hours.
      Frontotemporal nitroglycerin induced a significantly greater number of early
      onset migraine attacks with respect to the arm and forearm regions. In all cases,
      nitroglycerin applied to the frontotemporal region resulted in subsequent
      migraine, whereas there was a significant number of negative trials with
      nitroglycerin applied to the neck, arm, and forearm vs the frontotemporal area.
      It, therefore, appears that the trigeminal nerve endings in the affected
      frontotemporal region are particularly sensitive to the migraine-inducing effect
      of the nitrate. This suggests a peripheral neurogenic hypothesis of migraine
      genesis.

PMID- 7721577
TI  - SUNCT syndrome: a Hungarian case.
AB  - A Hungarian patient with short-lasting, unilateral, neuralgiform headache attacks
      with conjunctival injection and tearing (SUNCT) is presented in this paper. This
      male patient was first diagnosed as having first division trigeminal neuralgia.
      The location and duration of the attacks and the prominent accompanying autonomic
      features on the symptomatic side, such as conjunctival injection, lacrimation,
      nasal stuffiness, and the inefficacy of drugs, led to a reconsideration of the
      diagnosis. The pain paroxysms occurred frequently during a 3- to 4-month period,
      followed by a longer remission phase. Mechanical precipitating maneuvers were
      observed during bouts of pain. The clinical picture is reminiscent of the SUNCT
      syndrome, first described by Sjaastad et al in 1978. SUNCT and trigeminal
      neuralgia are in many ways similar, although, some decisive differences have also
      been noted. Further observations are needed to distinguish the two disorders and
      to clarify this syndrome as a new headache type or as a trigeminal neuralgia
      variant.

PMID- 7721578
TI  - Hemicrania continua: remitting stage evolved from the chronic form.
AB  - It is known that in hemicrania continua the chronic stage may be preceded by a
      remitting stage. In the present communication, the reverse sequence has been
      demonstrated, ie, a transition from the chronic to the remitting stage. The
      headache was characterized by a chronic pattern from the beginning until the
      commencement of indomethacin treatment, which provided long-lasting relief.
      Withdrawal of the drug resulted in reappearance of headaches with the same
      clinical features but in a remitting fashion. Resumption of indomethacin
      treatment had a dramatic effect on the remitting headaches. Such a temporal
      evolution of symptoms is consistent with the prevailing view that in a patient
      with hemicrania continua, there may be two temporal patterns.

PMID- 7721579
TI  - Noninvasive investigation of pericarotid syndrome: role of MR angiography in the
      diagnosis of internal carotid dissection.
AB  - A 52-year-old man presented with unilateral left periorbital and frontotemporal
      pain associated with a partial ipsilateral Horner's syndrome of the
      postganglionic type and representing a pericarotid syndrome. MRI demonstrated a
      perivascular subacute hematoma at the level of the cervical portion of the left
      internal carotid artery with a markedly reduced flow-void signal. MR angiography
      confirmed the narrowed lumen of the dissected cervical internal carotid artery.
      There was also a right-sided precavernous carotid aneurysm. Three months later
      the left-sided pain had subsided, with complete resolution of the hematoma and
      incomplete restoration of the left carotid lumen seen on MR angiography.
      Dissection of the carotid wall may cause the oculosympathetic paralysis by
      producing a lesion of the superior cervical ganglion, the internal carotid nerve,
      or the perivascular sympathetic plexus. Whereas in pericarotid syndrome the most
      common cause is cervical carotid dissection, Raeder's syndrome additionally
      involving parasellar cranial nerves, may be caused by any paracavernous/cavernous
      lesion, including neoplasms and intracranial carotid aneurysms. The clinical
      distinction is useful to determine the appropriate diagnostic investigation, in
      view of the different pathoanatomical localization and different disease
      spectrum. As demonstrated in the present case, the combination of MRI and MR
      angiography is a reliable noninvasive tool to investigate the differential
      diagnosis of pericarotid syndrome, accurately depicting occlusive, stenotic or
      aneurysmal lesions of the carotid artery. We suggest that intraarterial
      angiography is no longer necessary.

PMID- 7721580
TI  - Migraine and childhood head trauma.

PMID- 7721581
TI  - Winning a sweepstakes does not cure migraine.

PMID- 7721583
TI  - Geographic variation in rates of selected surgical procedures within Los Angeles
      County.
AB  - OBJECTIVE: We explore the contribution of income and ethnicity to geographic
      variation in utilization of surgical procedures. DATA SOURCES/STUDY SETTING: We
      assessed the use of eight procedures from 1986 through 1988 among residents of
      Los Angeles County using data from the California Discharge Dataset, the 1980
      census, and other secondary sources. Procedures chosen for evaluation were
      coronary artery bypass grafting (CABG), coronary artery angioplasty, permanent
      pacemaker insertion, mastectomy, simple hysterectomy, transurethral prostate
      resection (TURP), carotid endarterectomy, and appendectomy. STUDY DESIGN: The
      amount of inter-zip code variation for each procedure was first measured using
      various estimates including the analysis of variance coefficient of variation
      (CVA). Population-weighted multivariate regression analysis was used to model
      variation in age- and gender-adjusted rates of procedure use among 236
      residential zip codes. PRINCIPAL FINDINGS: Highest-variation procedures were
      coronary artery angioplasty (CVA = .392) and carotid endarterectomy (CVA = .374).
      The procedures with the lowest degree of variation were cardiac pacemaker
      implantation (CVA = .194) and hysterectomy (CVA = .195). Variation was
      significantly related to income (carotid endarterectomy) and either African
      American or Latino zip code ethnicity for all procedures except pacemaker
      implantation. For all procedures except appendectomy, the direction of the effect
      was toward fewer procedures with lower income. However, the effect of African
      American or Latino population ethnicity varied. CONCLUSIONS: In this large urban
      area both population ethnicity and socioeconomic status are significantly
      associated with the geographic utilization of selected surgical procedures.

PMID- 7721582
TI  - Excess acute care bed capacity and its causes: the experience of New York State.
AB  - OBJECTIVE: The study was developed to identify numbers of excess hospital medical
      surgical and pediatric bed capacity and the variables that produce them in the
      counties of New York State. DATA SOURCES/STUDY SETTING: Data were collected from
      New York's Statewide Planning and Research Cooperative System (SPARCS) for 1991.
      This system includes data for all hospital discharges in New York State by
      county. The counties of New York State include a full range of urban, suburban,
      and rural settings. STUDY DESIGN: A methodology was developed for projecting
      excess numbers of acute medical-surgical and pediatric beds. The impact of
      utilization variables (such as hospital discharge rates and lengths of stay) on
      bed levels were analyzed, as well as the effects of demographic, social, and
      health care resource availability. DATA COLLECTION/EXTRACTION METHODS: Data were
      collected through discharge abstracts provided by hospitals in New York State.
      PRINCIPAL FINDINGS: The data demonstrated that hospital discharges and lengths of
      stay contributed to excess utilization at different levels in New York State
      counties. The data also identified relationships between lower incomes and
      educational levels, as well as larger supplies of physicians and high-variation
      discharges, and excess beds. CONCLUSIONS: The causes of excess hospital beds
      varied considerably among communities in New York State; each community must
      develop its own approach to this problem.

PMID- 7721584
TI  - Black/white differences in prenatal care utilization: an assessment of
      predisposing and enabling factors.
AB  - OBJECTIVE: This article reports on analysis of the predisposing and enabling
      factors that affect black/white differences in utilization of prenatal care
      services. DATA SOURCES: We use a secondary data source from a survey conducted by
      the Michigan Department of Public Health. STUDY DESIGN: The study uses
      multivariate analysis methods to examine black/white differences in (1) total
      number of prenatal care visits, (2) timing of start of prenatal care, and (3)
      adequacy of care received. We use the model advanced by Aday, Andersen, and
      Fleming (1980) to examine the effect of enabling and predisposing factors on
      black/white differences in prenatal care utilization. DATA COLLECTION: A
      questionnaire was administered to all women who delivered in Michigan hospitals
      with an obstetrical unit. PRINCIPAL FINDINGS: Enabling factors fully accounted
      for black/white differences in timing of start of prenatal care; however, the
      model could not fully account for black/white differences in the total number or
      the adequacy of prenatal care received. CONCLUSION: Although there are no
      black/white differences in the initiation of prenatal care, black women are still
      less likely to receive adequate care as measured by the Kessner index, or to have
      as many total prenatal care contacts as white women. It is possible that barriers
      within the health care system that could not be assessed in this study may
      account for the differences we observed. Future research should consider the
      characteristics of the health care system that may account for the unwillingness
      or inability of black women to continue to receive care once they initiate
      prenatal care.

PMID- 7721585
TI  - Service mix in the hospital outpatient department: implications for Medicare
      payment reform.
AB  - OBJECTIVE: To determine if implementation of a PPS for Medicare hospital
      outpatient department (HOPD) services will have distributional consequences
      across hospital types and regions, this analysis assesses variation in service
      mix and the provision of high-technology services in the HOPD. DATA: HCFA's 1990
      claims file for a 5 percent random sample of Medicare beneficiaries using the
      HOPD was merged, by hospital provider number, with various HCFA hospital
      characteristic files. STUDY DESIGN: Hospital characteristics examined are
      urban/rural location, teaching status, disproportionate-share status, and bed
      size. Two analyses of HOPD services are presented: mix of services provided and
      the provision of high-technology services. The mix of services is measured by the
      percentage of services in each of 14 type-of-service categories (e.g., medical
      visits, advanced imaging services, diagnostic testing services). Technology
      provision is measured by the percentage of hospitals providing selected high
      technology services. FINDINGS/CONCLUSIONS: The findings suggest that the role
      hospital types play in providing HOPD services warrants consideration in
      establishing a PPS. HOPDs in major teaching hospitals and hospitals serving a
      disproportionate share of the poor play an important role in providing routine
      visits. HOPDs in both major and minor teaching hospitals are important providers
      of high-technology services. Other findings have implications for the structure
      of an HOPD PPS as well. First, over half of the services provided in the HOPD are
      laboratory tests and HOPDs may have limited control over these services since
      they are often for patients referred from local physician offices. Second,
      service mix and technology provision vary markedly among regions, suggesting the
      need for a transition to prospective payment. Third, the organization of service
      supply in a region may affect service provision in the HOPD suggesting that an
      HOPD PPS needs to be coordinated with payment policies in competing sites of care
      (e.g., ambulatory surgical centers).

PMID- 7721586
TI  - Which physicians limit their Medicaid participation, and why.
AB  - OBJECTIVE: This study identifies factors differentiating Medicaid participating
      physicians who accept all Medicaid patients from those limiting their Medicaid
      participation. DATA SOURCES: Data come from periodic telephone surveys of random
      samples of physicians conducted by the American Medical Association (AMA). STUDY
      DESIGN: Surveys conducted in 1990-1993 were pooled to form a sample of 4,188
      Medicaid-participating office-based physicians. Respondents were classified as
      accepting all Medicaid patients or as limiting their Medicaid participation.
      Descriptive statistics are used to examine differences between these groups with
      respect to selected personal, practice, community, and reimbursement variables.
      Logistic regression analysis is used to identify factors associated with
      physicians accepting all Medicaid patients or limiting their Medicaid
      participation in some way. DATA COLLECTION METHODS: Survey data were supplemented
      with 1990 census data, 1990 AMA Physician Masterfile data, and 1989 data on
      physician payment levels. PRINCIPAL FINDINGS: Less than half of Medicaid
      participating physicians and only about one-third of participating primary care
      physicians accept all Medicaid patients. Higher Medicaid fees are associated with
      physicians participating fully, but the marginal effects of changes in fees on
      the probability of physicians participating fully is small. CONCLUSIONS:
      Increases in Medicaid reimbursement aimed at primary care physicians or those in
      underserved areas may convert limited participants into full participants and, in
      so doing, improve the access of Medicaid eligibles to care. The increases in
      payment level needed to increase the proportion of physicians participating fully
      would be substantial, however, and may not be politically feasible.

PMID- 7721587
TI  - Case mix of home health patients under capitated and fee-for-service payment.
AB  - OBJECTIVE: We compare case mix of Medicare home health patients under HMO and FFS
      payment. STUDY DESIGN: A pseudo-experimental design was employed to study case
      mix using three types of Medicare-certified home health agencies (HHAs): HMO
      owned agencies, pure FFS agencies that admit few Medicare HMO patients (less than
      5 percent of admissions are Medicare HMO patients), and mixed (or contractual)
      agencies that admit at least 15 Medicare FFS patients and 15 Medicare HMO
      patients per month. SAMPLES OF PROVIDERS AND PATIENTS: Random samples of Medicare
      aged patients (> or = 65 years) were selected at admission between June 1989 and
      November 1991 from the 38 study HHAs. Sample sizes by agency type were: 308
      patients from 9 HMO-owned agencies; 529 patients from 15 pure FFS agencies; and
      381 HMO patients and 414 FFS patients from 14 contractual agencies. DATA: Primary
      longitudinal data were prospectively collected at admission for all patients on
      health status indicators, demographics, admission source, and home environment.
      MEASURES: The most important case-mix measures were functional and physiologic
      indicators of health status, including (instrumental) activities of daily living
      ([I]ADLs). Selected indicators of demographic variables, prior location, living
      situation, characteristics of informal caregivers, mental/behavioral factors, and
      resource needs were also used. PRINCIPAL FINDINGS: (a) The case mix of Medicare
      FFS patients compared with Medicare HMO patients was more intense in terms of
      impairments in ADLs, IADLs, and various physiologic conditions. Pressure ulcers
      as well as neurological and orthopedic impairments requiring rehabilitation care
      were also more prevalent among FFS patients. (b) Relative to HMO patients
      admitted to contractual agencies, HMO patients admitted to HMO-owned agencies
      were moderately more dependent in ADLs and IADLs. However, only 62 percent of HMO
      patients admitted to HMO-owned agencies, in contrast to 77 percent of HMO
      patients admitted to contractual agencies, had been hospitalized during the 30
      days prior to home health admission. (c) In all, the case mix of patients
      receiving care from HMO-owned agencies is more heterogeneous than the case mix of
      HMO patients receiving care from contractual agencies. CONCLUSIONS: The case-mix
      (and selected utilization) findings indicate that HMOs use home health care
      differently than does the FFS sector. The greater diversity of case mix for HMO
      owned agencies and the narrower or less diverse case mix that characterizes HMO
      patients receiving home care on a contractual basis point to the likelihood of
      cost differences among the two types of HMO patients and FFS patients, and raise
      the question of possible outcome differences.

PMID- 7721588
TI  - Race matters.

PMID- 7721589
TI  - The role of race/ethnicity and social class in minority health status.
AB  - Minority health is often considered as a unitary phenomenon; it is often assumed
      that the health status of minority groups in the United States is similar across
      groups and much worse than that for whites. Yet the reality is extraordinary
      diversity. Racial/ethnic groups differ greatly both among and within themselves
      with regard to health status and with regard to a large number of other indices.
      Mortality rates around the world generally show an inverse relationship with
      social class. While this generally holds true in the United States as well, once
      again we see a strong interaction with race/ethnicity. However, the mediating
      factors between race/ethnicity and social class, and health status are not well
      understood. Especially in the face of health care reform, a broad-based research
      agenda needs to be undertaken so that any restructuring of the health care
      delivery system is informed by empirical information.

PMID- 7721590
TI  - Beyond class, race, and ethnicity: deprivation and health in Britain.
AB  - The concepts of class, race, and ethnicity figure prominently in health services
      research in Britain. Occupational class has been employed for nearly a century to
      investigate social inequalities in health and access to care. More recently,
      researchers have identified differences in health status and utilization between
      ethnic groups. This article examines how these constructs are defined in Britain
      and identifies some key research associated with them. It also draws attention to
      the considerable problems in using class and ethnicity to stratify the
      population. The authors conclude that a new approach that directly measures
      individuals' material and social resources needs to be developed.

PMID- 7721591
TI  - The roles of race and socioeconomic factors in health services research.
AB  - For decades data have been collected comparing health care in racial and ethnic
      groups. The use of such groups in health services research assumes that standard,
      reliable, and valid definitions of race and ethnicity exist and that these
      definitions are used consistently. In fact, race is a term often used, but ill
      defined. It can incorporate biological, social, and cultural characteristics of
      patients and can refer to both genetic and behavioral traits. Various
      investigators have reported differences between racial and ethnic groups in
      health status, disease manifestation and outcome, resource utilization, and
      health care access, often specifying neither a definition of race nor the
      measurement they used to classify their study populations. The role of race as an
      explanatory variable in health services research requires greater scrutiny than
      many researchers currently provide. Many studies use race as a proxy for other
      socioeconomic factors not collected in the research effort. This article explores
      the ambiguities about race as an explanatory variable that render such research
      difficult to interpret. We suggest that health services researchers focus on
      nonracial socioeconomic characteristics that might be both more informative and
      more useful in guiding policy formation.

PMID- 7721592
TI  - Recruitment and retention of subjects for a longitudinal cancer prevention study
      in an inner-city black community.
AB  - Recruiting and retaining subjects for longitudinal prevention trials is
      challenging. The inherent difficulties are compounded when the trial is to take
      place in a low-income minority community, since prevention is a low priority
      among residents of such communities, and research is viewed with suspicion. We
      present our experiences in attempting to recruit and retain low-income black
      women living in inner-city Atlanta for a trial of an educational intervention to
      promote screening for cancer. The intervention was conducted in the home by
      trained lay health workers. We found that recruitment was more successful when we
      recruited directly from the community than when we recruited from the patient
      registry of a primary health care center. The attrition rate over an 18-month
      period was high. Among members of the intervention group, those retained in the
      study tended to be wealthier and better educated and were more likely to be
      married and employed than those who dropped out. It seems probable that women of
      lower socioeconomic status found our intervention to be intrusive or burdensome.
      Among the controls, socioeconomic factors did not discriminate between those who
      completed the study and those who did not; loss to follow-up in this group was
      associated only with younger age. In conducting research of this type in low
      income minority communities, special attention must be given to issues of
      recruitment and retention if the validity of the study is to be preserved.

PMID- 7721593
TI  - Conceptualizing race in economic models of medical utilization: a case study of
      community-based elders and the emergency room.
AB  - There is no consensus on the appropriate conceptualization of race in economic
      models of health care. This is because race is rarely the primary focus for
      analysis of the market. This article presents an alternative framework for
      conceptualizing race in health economic models. A case study is analyzed to
      illustrate the value of the alternative conceptualization. The case study
      findings clearly document the importance of model stratification according to
      race. Moreover, the findings indicate that empirical results are improved when
      medical utilization models are refined in a way that reflects the unique
      experiences of the population that is studied.

PMID- 7721594
TI  - Conducting an assessment of health needs and resources in a racial/ethnic
      minority community.
AB  - This article examines strategies and methodologic issues for researchers to
      consider when conducting community-based research within a racial/ethnic minority
      community. Members of minority communities have considerable skepticism about the
      health care system and researchers who work under its auspices. To facilitate
      quality research, it is necessary to build a mutually beneficial partnership
      between the community and researchers. Suggested strategies for accomplishing
      this goal, such as seeking out information on the social and political forces
      shaping the community and developing the community's capacity to undertake
      research of this type, are described. Methodologic issues include the importance
      of community input in defining the minority population group and its leadership,
      the benefits and limitations of conducting comparative analysis, and the need for
      measurement tools and techniques that are culturally and socially appropriate.
      Minority and nonminority researchers must make a concerted effort to gain
      knowledge of and respect for a community whose culture, values, and beliefs may
      differ from their own.

PMID- 7721595
TI  - Racial/ethnic differences in health care utilization of cardiovascular
      procedures: a review of the evidence.
AB  - Studies based on a variety of primary data sets have consistently demonstrated
      that African Americans are about half as likely as whites to receive
      interventional therapy for coronary artery disease. Neither disease severity per
      se nor access to hospitals performing these procedures accounts for this finding.
      Likewise, available measures of income and ability to pay, including insurance
      status, do not explain the differences. Subtle personal factors, including
      physician bias and the willingness of patients to accept referral for surgery,
      may be important but have not as yet been measured. These findings present a
      challenge to the presumed equality in access to health care within the United
      States medical system. A new generation of health services research studies will
      be required to provide definitive reasons for this important disparity in
      treatment.

PMID- 7721597
TI  - An evaluation of mammography beliefs using a decision model.
AB  - The purpose of this study was to identify factors that contribute to a group of
      working women's decision related to mammography. The study was guided by a
      decision model called the Multiattribute Utility Model. Exploratory interviews
      were conducted among 36 women to identify positive and negative factors
      associated with the mammography decision. Eighteen factors emerged and were
      categorized into three broad areas: Knowledge and Attitudes (Confidence in
      Efficacy, Personal Risk, Other Means of Knowing, Fear of Cancer/Treatment, Belief
      in Fate, Embarrassment), Issues Related to Participation (Accessibility and
      Convenience, Difficulty Arranging, Time, Cost, Pain, Radiation), and Social
      Concerns (Role Model, Responsibility to Self, Responsibility to Others,
      Family/Friends' Influence, Societal Influences, Health Care Providers'
      Influence). This information served as the basis of a survey among 87 women to
      determine the importance of these factors. Seven factors emerged as significantly
      different between compliers and noncompliers. In order of significance, they were
      Difficulty Arranging, Fear of Cancer/Treatment, Cost, Accessibility and
      Convenience, Time, Other Means of Knowing, and Influence of Health Care Provider.
      The predictive validity of this analysis was 85%. Implications of findings are
      discussed.

PMID- 7721596
TI  - The efficacy of primary care for vulnerable population groups.
AB  - This article reviews the existing literature on the efficacy of primary care with
      an emphasis on the evaluation of primary care for vulnerable populations: groups
      whose demographic, geographic, or economic characteristics impede or prevent
      their access to health care services. A significant portion of the literature
      derives from studies of poor and underserved populations. However, to construct a
      more complete evaluation of primary care services, the authors cite literature
      that has examined both advantaged and disadvantaged populations. Even then the
      literature is incomplete, at best. The article describes a definition of primary
      care suitable for policy analysis and formulation, reviews evidence on the
      efficacy of care that meets that definition, and concludes that widespread use of
      primary care services is likely to result in improved patient satisfaction and
      health status.

PMID- 7721598
TI  - The relative effects of perceived personal control and responsibility on health
      and health-related behaviors in young and middle-aged adults.
AB  - We examined whether perceptions of personal control over health and perceptions
      of personal responsibility for well-being were related, whether they had
      independent or interactive effects on health and health-related behaviors, and
      whether the effects of the perceptions varied by income. Young and middle-aged
      employees of a technology company (N = 186; aged 20-63) completed a questionnaire
      about perceived control and responsibility, health, health-related behaviors, and
      demographic information. Correlation analysis indicated that the perceived
      control and perceived responsibility variables were unrelated. Regression
      analysis indicated that a main effect of perceived control--but not
      responsibility--contributed significantly to the explanation of variance in
      health and several health-related behaviors (medical checkup, breast self
      examination, exercise, and health promotion program membership). Perceived
      control and responsibility did not interact in their influences over health and
      behavior; however, the hypothesis that the variables would interact with income
      was partially confirmed. Overall, the results suggest that the sense of control
      rather than sense of responsibility should be targeted for health promotion
      efforts.

PMID- 7721599
TI  - Contraceptive and condom use adoption and maintenance: a stage paradigm approach.
AB  - The Transtheoretical Model of Behavior Change was examined for its applicability
      to contraceptive and condom use adoption and maintenance using N = 248
      heterosexually active college-age men and women. The model posits that
      individuals do not go directly from old behaviors to new behaviors to new
      behaviors, but progress through a sequence of stages: precontemplation,
      contemplation, preparation, action, and maintenance. The stages of change offer a
      temporal dimension that provides information regarding when a particular shift in
      attitudes, intentions, and behavior may occur. The model also postulates a set of
      or outcome variables--the pros and cons of change and self-efficacy. The results
      demonstrated that individuals were furthest along in the stages of change for
      general contraceptive use, followed closely by condom use with other (e.g.,
      casual) partners, and then condom use with main partners. Although no sex
      differences were found for the stages for the three separate contraceptive
      behaviors, males and females differed on the pros and cons and levels of self
      efficacy when engaging in intercourse with the two types of partners.
      MANOVA/ANOVA results indicated that the relationship between stages and other
      constructs follows predicted patterns suggesting that the transtheoretical model
      may provide a useful framework or paradigm for understanding contraceptive and
      condom use behavior.

PMID- 7721600
TI  - Health behavior segmentation and campaign planning to reduce cardiovascular
      disease risk among Hispanics.
AB  - Using the social marketing principle of audience segmentation, a Hispanic
      audience was disaggregated to examine heterogeneous behaviors and lifestyles that
      could guide planning for public information campaigns designed to reduce
      cardiovascular disease (CVD) risk. Signal detection analysis resulted in six
      mutually exclusive subgroups, based on self-reported behavioral changes to
      improve health. Subgroups differed significantly in communication, behavioral,
      psychological, and demographic dimensions, indicating they may require unique
      campaign planning strategies. To determine whether subgroups were meaningful
      relative to external health-related criteria, they were compared as to health
      knowledge and status on cardiovascular disease risk factors. The results showed
      significant differences among audience subgroups in plasma high-density
      lipoprotein levels and hypertensive status. Results are discussed in terms of
      their implications for campaign planning and the need for public health campaigns
      to diversify strategies when targeting Hispanic audiences.

PMID- 7721601
TI  - Distinguishing starters from nonstarters in an employee physical activity
      incentive program.
AB  - Although the vast majority of Americans who are physically active are likely to
      extol its many physical, psychological, and social values, research indicates
      that approximately fifty percent of individuals who start a formal physical
      activity program will drop out in six months or less. The present study employed
      stepwise discriminant analytical techniques in an attempt to distinguish starters
      from nonstarters in an innovative employee physical activity incentive program.
      The results indicated that a combination of health beliefs and lifestyle
      characteristics, health locus of control expectancies, and physiological
      characteristics accurately discriminated 81.7% of the starters and nonstarters.
      It was concluded that physical activity programs need to be designed,
      implemented, and marketed in such a manner as to attract individuals who are
      sedentary, smoke, are unable to cope with home-mediated stress, have an external
      health locus of control expectancy, and/or have a high cardiovascular disease
      risk factor profile.

PMID- 7721602
TI  - Cancer risk reduction in Mexican American women: the role of acculturation,
      education, and health risk factors.
AB  - This article describes a two-factor schema for the development of culturally
      appropriate cancer risk reduction interventions for Mexican American women.
      Regarding this approach, risk factors for two major cancer areas are reviewed:
      cigarette smoking and obesity/diet. We first describe a schema that facilitates
      the planning of strategies associated with preferred health interventions and
      preventive approaches for cancer risk reduction with Mexican American and other
      Latino/Hispanic persons. This schema examines Acculturation and Education as key
      factors that should be considered in developing health education messages and
      interventions that are culturally and educationally appropriate to the identified
      subpopulations of Hispanics in terms of language and informational content of the
      message and in terms of psychological factors related to health behavior change.
      Empirical data from a community sample is presented for the purpose of
      illustrating the validity of this schema. Then we review studies that examine the
      effect of acculturation on the distribution of the risk factors, based on studies
      in the current literature. Here we note the target group of women with the
      highest risk, based on the available information on Acculturation and other
      sociodemographic factors. Additionally, an illustration is presented where
      information and the concepts offered by the two-factor schema facilitate the
      analysis of (a) health education message needs and (b) needed behavior change,
      thus pointing to (c) more appropriate health promotion strategies for targeted
      Hispanic/Latino individuals or groups. The information described in this article
      aims to help program planners, researchers, and health educators in the design of
      more effective programs of health intervention for Mexican American and other
      Hispanic/Latino women.

PMID- 7721603
TI  - In-home injury prevention practices for infants and toddlers: the role of
      parental beliefs, barriers, and housing quality.
AB  - The present research was designed to contribute to the empirical literature on
      the scope and determinants of parents' injury prevention practices among families
      living in disadvantaged, urban areas. One hundred fifty mothers were interviewed
      about their living environment when they brought their children (ages 6-36
      months) to a hospital-based, pediatric primary care clinic. Only 37% of
      respondents reported that they knew their hot water temperature was 125 degrees
      or less. A majority (59%) of families reported that they did not use stair gates.
      More than one fourth (27%) of respondents said they did not have smoke detectors.
      Mothers uniformly reported very favorable attitudes and beliefs and strong
      support from others for in-home injury prevention practices. Factors
      significantly associated with the number of injury prevention practices
      implemented were family income, housing quality, and environmental barriers.
      Instead of attempting solely to persuade parents about the value of injury
      prevention practices, skill-based interventions are needed to help parents
      overcome specific barriers that result from living in substandard housing and
      having very limited financial resources.

PMID- 7721604
TI  - An economic evaluation of four work site based cardiovascular risk factor
      interventions.
AB  - We used outcome data from a randomized work site intervention trial to examine
      the cost-effectiveness of four cardiovascular disease (CVD) risk reduction
      programs: health risk assessment (HRA), risk factor education (RFE), behavioral
      counseling (BC), and behavioral counseling plus incentives (BCI). Composite CVD
      risk scores were derived from measures of serum total cholesterol, blood
      pressure, number of cigarettes smoked, body mass index, and aerobic capacity. The
      economic evaluation of the programs focused on the subset of costs most sensitive
      to the differences between the interventions, and a sensitivity analysis examined
      some of the relevant cost variations. At the 6-month follow-up (i.e., the
      "action" or initiation stage of lifestyle change), the RFE, BC, and BCI
      interventions produced a significant reduction in cardiovascular risk.
      Incremental analyses demonstrated RFE to be more cost-effective, but not as
      clinically effective as BC; BC was more cost-effective than RFE when assessment
      costs were included, and BCI was judged to be the least cost-effective. At the 12
      month follow-up (i.e., the "maintenance" stage of lifestyle of change), BC was
      the only program found to produce a significant reduction in CVD risk.
      Individualized behavioral counseling was found to be a cost-effective strategy
      for the initiation and maintenance of CVD risk factor reduction.

PMID- 7721605
TI  - Examining a paradox: does religiosity contribute to positive birth outcomes in
      Mexican American populations?
AB  - A particularly interesting and consistent finding regarding the health of the
      Latino population is that Mexican American women, despite their relatively lower
      socioeconomic status, deliver significantly fewer low birth weight babies and
      lose fewer babies to all causes during infancy than do women of other ethnic
      groups. A central thesis of this discussion is that the religiosity and
      spirituality of many of these Latinas, a key factor in their culture, may protect
      them and their infants through the pre- and antenatal phases of life. We also
      suggest that lack of research, related to cultural similarities and differences
      in Hispanic/Latino subgroups, can lead to faulty or simplistic understanding
      regarding their health behavior and health status.

PMID- 7721606
TI  - The effect of the overall treatment time of fractionated irradiation on the tumor
      control probability of a human soft tissue sarcoma xenograft in nude mice.
AB  - PURPOSE: To study the impact of the overall treatment time of fractionated
      irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma
      xenograft growing in nude mice, as well as to compare the pretreatment potential
      doubling time (Tpot) of this tumor to the effective doubling time (Teff) derived
      from three different schedules of irradiation using the same total number of
      fractions with different overall treatment times. METHODS AND MATERIALS: The TCP
      was assessed using the TCD50 value (the 50% tumor control dose) as an end point.
      A total of 240 male nude mice, 7-8 weeks old were used in three experimental
      groups that received the same total number of fractions (30 fractions) with
      different overall treatment times. In group 1, the animals received three equal
      fractions/day for 10 consecutive days, in group 2 they received two equal
      fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30
      consecutive days. All irradiations were given under normal blood flow conditions
      to air breathing animals. The mean tumor diameter at the start of irradiation was
      7-8 mm. The mean interfraction intervals were from 8-24 h. The Tpot was measured
      using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to
      Teff. RESULTS: The TCD50 values of the three different treatment schedules were
      58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This
      difference in TCD50 values was significant (p < 0.05) between groups 1 and 2 (30
      fractions/10 days and 30 fractions/15 days) vs. group 3 (30 fractions/30 days).
      The loss in TCP due to the prolongation of the overall treatment time from 10
      days to 30 days was found to be 1.35-1.4 Gy/day. The pretreatment Tpot (2.4 days)
      was longer than the calculated Teff in groups 2 and 3 (1.35 days). CONCLUSION:
      Our data show a significant loss in TCP with prolongation of the overall
      treatment time. This is most probably due to an accelerated repopulation of tumor
      clonogens. The pretreatment Tpot of this tumor model does not reflect the actual
      doubling of the clonogens in a protracted regimen.

PMID- 7721607
TI  - Human chromosome-specific changes in a human-hamster hybrid cell line (AL)
      assessed by fluorescent in situ hybridization (FISH).
AB  - PURPOSE: To quantitatively assess all gamma-ray induced chromosomal changes
      confined to one human chromosome using fluorescence microscopy and in situ
      hybridization with a fluorescently labeled human chromosome specific nucleic acid
      probe. METHODS AND MATERIALS: Synchronized human-hamster hybrid cells containing
      human chromosome 11 were obtained by a modified mitotic shake-off procedure. G1
      phase cells (> 95%) were irradiated with 137Cs gamma rays (0, 0.5, 1.0, 1.5, 2.0,
      4.0, 6.0, 8.0, and 10.0 Gy) at a dose rate of 1.1 Gy/min and mitotic cells
      collected 16-20 h later; chromosomal spreads were prepared, denatured, and
      hybridized with a fluorescein-tagged nucleic acid probe against total human DNA.
      Chromosomes were examined by fluorescence microscopy and all categories of change
      involving the human chromosome 11 as target, recorded. RESULTS: Overall, of the
      3104 human-hamster hybrid cells examined, 82.1% were euploid, of which 88.6%
      contained one copy of human chromosome 11, 6.2% contained two copies, and 5.2%
      contained 0 copies. This is compatible with mitotic nondisjunction in a small
      fraction of cells. Of the remaining 17.9% of cells, 85.2% were tetraploid cells
      with two copies of human chromosome 11. For all aberrations involving human
      chromosome 11 there was a linear relationship between yield and absorbed dose of
      0.1 aberrations per chromosome per Gy. The yield of dicentrics, translocations,
      and terminal deletions that involve one lesion on the human chromosome was
      linear, while the yield of interstitial deletions that arise from two interacting
      lesions on the human chromosome was curvilinear. The frequencies of dicentrics
      and translocations were about equal, while there was a high (40-60%) incidence of
      incomplete exchanges between human and hamster chromosomes. CONCLUSIONS:
      Fluorescent in situ hybridization (FISH) procedures allow for the efficient
      detection of a broad range of induced changes in target chromosomes. Symmetrical
      exchanges induced in G1 (translocations) were readily scored and found to equate
      with the complementary asymmetrical exchanges (dicentrics). That is, nonlethal
      stable changes, which might be of concern in carcinogenic processes, complement
      lethal, unstable changes. Interstitial deletions that may contribute to the loss
      of antioncogenes as well as to lethality are also readily detected with enhanced
      levels detected at higher doses. The high level of induced terminal deletions and
      of incomplete dicentrics and translocations indicate a partial failure of
      interaction between lesions induced in human and hamster DNA, and suggest that
      such interspecies interactions lack the fidelity of intraspecies DNA lesion
      interactions. This suggests caution in the use of such model systems as
      indicators of human cell responsiveness.

PMID- 7721608
TI  - Quantitative magnetic resonance and isotopic imaging: early evaluation of
      radiation injury to the brain.
AB  - PURPOSE: Using magnetic resonance (MR) and isotopic imaging to investigate the
      cerebral alterations after highdose single-fraction irradiation on a pig model.
      We assessed the nuclear magnetic resonance (NMR) relaxation times as early
      markers of radiation injury to the healthy brain. METHODS AND MATERIALS: A total
      of 17 animals was studied; 15 irradiated and 2 unirradiated controls. Pigs were
      irradiated with a 12 MeV electron beam at a rate of 2 Gy/min. Ten animals
      received 40 Gy at the 90% isodose, five animals received 60 Gy, and two animals
      were unirradiated. The follow-up intervals ranged from 2 days to 6 months. T1
      weighted scans, T2-weighted scans, and scintigrams were performed on all animals
      to study neurological abnormalities, cerebral blood flow, and blood-brain barrier
      (BBB) integrity. T1 and T2 relaxation times were measured in selected regions of
      interest (ROIs) within the irradiated and contralateral hemispheres. A ratio T1
      after irradiation/T1 before irradiation, and a ratio T2 after irradiation/T2
      before irradiation, were calculated, pooled for each dose group, and followed as
      a function of time after irradiation. RESULTS: Scintigraphy visualized the brain
      perfusion defect and BBB disruption in all irradiated brains. The ratio T2 after
      irradiation/T2 before irradiation was proportional to the effective dose
      received. The T2 ratio kinetics could be analyzed in three phases:an immediate
      and transient phase, two long-lasting phases, which preceded compression of the
      irradiated lateral ventricle, and edema and necrosis at later stages of radiation
      injury, respectively. The magnetic resonance imaging (MRI) observations
      correlated well with histological analysis. CONCLUSION: The results show that
      quantitative imaging is a sensitive in vivo method for early detection of
      cerebral radiation injury. The reliability and dose dependence of T2 relaxation
      time may offer new opportunities to detect and understand brain pathophysiology
      after high-dose single-fraction irradiation.

PMID- 7721609
TI  - Tumor blood flow measurements using coincidence counting on patients treated with
      neutrons.
AB  - PURPOSE: The purpose of this work was to measure blood flow in tumors using a
      coincidence counting technique on patients undergoing treatment with neutrons.
      METHODS AND MATERIALS: The half-time, Tw, for the washout of 15O from neutron
      activated tumors was measured with two 10 cm NaI(Tl) crystals coupled to a PC
      based coincidence counting system. Blood flow measurements were made in 33
      patients, 19 of whom had cancers of the head and neck region, 6 had breast
      cancer, 5 had sarcomas, and 3 patients had mesotheliomas. RESULTS: Blood flow as
      indicated by Tw of mobile 15O formed by neutron activation could be readily
      determined in tumors of patients undergoing neutron radiotherapy. The general
      reduction in the value for Tw was noted towards the end of treatment and did not
      seem to be dependent on the initial tumor volume. There was a tendency for larger
      lesions to be associated with longer half-times of 15O washout. CONCLUSION: It
      appears possible to obtain a reasonable estimate of tumor blood flow using a
      simple coincidence counting technique. In view of the large variation in blood
      flow between tumors, it did not appear to be possible to identify potentially
      hypoxic tumors that would respond to neutron therapy.

PMID- 7721610
TI  - Comparisons of radioiodoestradiol blood-tissue exchange after intravenous or
      intraarterial injection.
AB  - PURPOSE: Our study determines and compares how the major organs of large animals
      handle exogenous halogenated bioactive sex steroids within the first minutes
      after their i.v. or i.a. injection. The rationale is that an understanding is
      needed of the acute physiological events because they affect decisions for how to
      optimize delivery of radiohalogenated sex steroid receptor ligands for purposes
      of medical imaging and modes of radiotherapy. METHODS AND MATERIALS: We used an
      indicator dilution technique that allows monitoring of blood-tissue exchange of
      radioactivity in a continuous manner in anesthetized surgically prepared swine.
      RESULTS: In swine, with by-passed liver circulation, the lungs allow the vast
      majority of [I-125]-16 alpha-iodo-17 beta-estradiol ([I-125]E) to be extracted
      from the blood perfusing the lung in the initial transit after i.v. injection in
      vivo. Similar outcome was observed for most major organs, including the CNS,
      intestines, spleen, peripheral appendages, and kidneys after i.a. injection of [I
      125]E in vivo. However, within minutes the organs released the [I-125]E in its
      original chemical form back into the vascular system, with the exception of
      estrogen receptor (ER) rich tissues and the kidneys that retained the [I-125]E in
      its original form, although in the kidneys a nonpolar metabolite also
      accumulated. CONCLUSION: Our experiments confirm in a large animal model that
      radioiodoestradiol can be sequestered or concentrated in ER-rich sites. The liver
      and sex steroid receptor-rich organs modify considerably, by metabolism and
      sequestration, respectively, the acute distribution of bioactive steroids. Our
      data indicate potential for detection of ER in vivo in hormone-sensitive tumors,
      that is, in breast and endometrial cancers, and offer improved understanding of
      the recent studies in subjects with breast cancer that demonstrated that receptor
      imaging in vivo of steroid receptors with high-affinity radiolabeled ligands is
      possible in a clinical setting.

PMID- 7721611
TI  - Direct measurement of intratumor dose-rate distributions in experimental
      xenografts treated with 90Y-labeled radioimmunotherapy.
AB  - PURPOSE: To measure, quantify, and evaluate the planar dose-rate distribution for
      human tumor xenografts implanted into mice that are treated with 90Y-labeled
      monoclonal antibodies or bispecific antibodies and 90Y-labeled haptens. METHODS
      AND MATERIALS: Twenty-five LS174T human colon carcinoma tumors grown
      subcutaneously in nude mice were treated with 90Y by either directly labeled
      ZCE025 or bispecific ECA001-DBX antibody systems. A simple, quick technique using
      GAF radiochromic medium determined the dose-rate distribution in a plane passing
      through the tumor center. The dose-rate distribution is generated from exposure
      to activity situated in one-half of the tumor (0.045 to 0.83 g). RESULTS: Planar
      dose-rate distributions were obtained from the tumor xenografts. Planar dose-rate
      histograms were computed along with the coefficients of variance and skewness of
      the distributions. The observed dose-rate distributions were quantitatively
      compared to those calculated for a uniformly distributed activity in a half
      ellipsoid of the same volume and approximate shape as the tumor half. The
      observed dose-rate distributions were usually broader with a more positive
      coefficient of skewness than the dose-rate distributions calculated from the
      uniformly active half-ellipsoids. For 90Y, tumor shape plays an important role in
      determining the minimum tumor dose. For these tumors, the tumor minimum dose-rate
      is always observed along the edge, usually where the edge curvature is most
      convex. Larger tumors tended to have broader dose-rate distributions and more
      positive coefficients of skewness. Exceptions to this trend were associated with
      dose-rate maxima displaced from the central regions due to activity heterogeneity
      or tumor size greatly exceeding the range of emission. Calculations for dose rate
      from the conventional Medical Internal Radiation Dose (MIRD) formulation exceeded
      the average and minimum dose rate derived from radiochromic media. The
      coefficient of skewness became more positive for increasing time between
      injection and tumor excision, consistent with the activity evolving into a more
      uniform activity distribution. CONCLUSION: Using radiochromic media to measure
      the spatial dose-rate distribution is a valuable method for comparing the dose
      rate heterogeneity among experimental tumor xenografts in animals treated with
      radiolabeled antibodies. Tumor size (relative to the particle range) and changes
      in activity distribution radiolabeled antibodies. Tumor size (relative to the
      particle range) and changes in activity distribution affect the dose-rate
      distribution that are reflected by changes in the coefficients of skewness and
      variation of the dose-rate area histogram. The increase in coefficients of
      variation and skewness with tumor size and time results from the size of the 90Y
      beta particle penetration range that either exceeds or is comparable to the tumor
      dimensions. The minimum dose rate is more dependent, relative to the average and
      the maximum dose rates, on the curvature of the tumor surface.

PMID- 7721612
TI  - Dose distribution considerations of medium energy electron beams at extended
      source-to-surface distance.
AB  - PURPOSE: To determine the effects of extended source-to-surface distance (SSD) on
      dose distributions for a range of medium energy electron beams and cone sizes.
      METHODS AND MATERIALS: The depth-dose curves and isodose distributions of 6 MeV,
      10 MeV, and 14 MeV electron beams from a dual photon and multielectron energies
      linear accelerator were studied. To examine the influence of cone size, the
      smallest and the largest cone sizes available were used. Measurements were
      carried out in a water phantom with the water surface set at three different SSDs
      from 101 to 116 cm. RESULTS: In the region between the phantom surface and the
      depth of maximum dose, the depth-dose decreases as the SSD increases for all
      electron beam energies. The effects of extended SSD in the region beyond the
      depth of maximum dose are unobservable and, hence, considered minimal. Extended
      SSD effects are apparent for higher electron beam energy with small cone size
      causing the depth of maximum dose and the rapid dose fall-off region to shift
      deeper into the phantom. However, the change in the depth-dose curve is small. On
      the other hand, the rapid dose fall-off region is essentially unaltered when the
      large cone is used. The penumbra enlarges and electron beam flatness deteriorates
      with increasing SSD.

PMID- 7721613
TI  - Neurological observations after local irradiation and hyperthermia of rat
      lumbosacral spinal cord.
AB  - PURPOSE: Investigation of the effects of hyperthermia on the radiation response
      of rat lumbosacral spinal cord with respect to: (a) incidence of paralysis, (b)
      latency, (c) histopathology, and (d) tumor induction. METHODS AND MATERIALS: Rat
      lumbosacral spinal cord with the cauda equina was single-dose irradiated with 15
      to 32 Gy of x-rays. Hyperthermia for 30 min at a spinal cord temperature of 41.1,
      42.3, and 42.6 +/- 0.4 degrees C was applied 5 to 10 min after irradiation by
      means of a 434 MHz microwave applicator. Animals were observed for 21 months
      while recording myelopathy and development of tumors. RESULTS: The latent period
      for hind leg paralysis decreased with increasing radiation dose from 359 +/- 31
      days (n = 9) after 20 Gy to 200 +/- 4 days (n = 5) after 32 Gy. Hyperthermia
      enhanced the radiation response of the lumbosacral spinal cord as evidenced by
      shortening of the latent period for paralysis and a decrease in the biological
      effective dose. After 20 Gy followed by 30 min 41.1 degrees C, latency was
      diminished to 214 +/- 16 days (n = 7, p < 0.001 vs. 20 Gy alone). The ED50 was
      21.1 Gy, which was diminished to values between 16 and 17 Gy if radiation was
      followed by hyperthermia, giving a thermal enhancement ratio between 1.24 and
      1.32. Histopathological examination of the spinal cord after combined treatment
      of x-rays and hyperthermia showed necrosis of nerve roots. Irradiation with 16,
      20, 24, and 28 Gy (n = 77) alone led to tumor induction in 17 +/- 8% of the
      animals (pooled data). If followed by hyperthermia (n = 96), it was increased to
      33 +/- 12% (p < 0.01). Most tumors induced by radiation and hyperthermia were
      sarcomas. CONCLUSION: First, the radiation response of rat lumbosacral spinal
      cord was enhanced by heat. Second, latency for paralysis was shortened in the
      lower dose range. Third, no difference in pathology between x-rays alone or in
      combination with hyperthermia. Fourth, hyperthermia did increase radiation
      carcinogenesis.

PMID- 7721614
TI  - Phase II trial of hormonal cytoreduction with megestrol and diethylstilbestrol in
      conjunction with radiotherapy for carcinoma of the prostate: outcome results of
      RTOG 83-07.
AB  - PURPOSE: RTOG 83-07 is a Phase II randomized protocol designed to compare the
      efficacy and toxicity of Megestrol vs. Diethylstilbestrol (DES) used as
      cytoreductive agents prior to and during radiotherapy. The end points of this
      study include tumor clearance rate, effect on serum testosterone, loco-regional
      control, disease-free interval, and survival. METHODS AND MATERIALS: Eligible
      patients were those with histologically confirmed locally advanced
      adenocarcinoma, clinical Stage B2 (T2B) and C (T3) without regional lymph node
      involvement, or with lymph node involvement limited to the pelvis. Patients were
      stratified by clinical stage, histological grade, and nodal status, and were
      randomized to receive either Megestrol 40 mg three times per day by mouth, or
      Diethylstilbestrol 1 mg three times per day by mouth. The drugs were started 2
      months prior to initiation of radiotherapy and were continued throughout the
      radiotherapy course. Radiotherapy consisted of 44-46 Gy, 1.8-2 Gy per day to the
      regional lymphatics, followed by a boost to the prostate consisting of 20-25 Gy,
      1.8-2 Gy per day, to a total of 65-70 Gy. Serum testosterone levels were recorded
      throughout the treatment course. Tumor response was assessed clinically and
      radiographically (CT scan). From March 1983 through June 1986 a total of 203
      patients were accessioned to the study; 198 were analyzable. RESULTS: Correlation
      of the incidence of drug-related toxicity and treatment arm assignment revealed a
      significantly higher incidence of complications in the Diethylstilbestrol (DES)
      arm. The most prominent were the differences in the incidence of gynecomastia
      (55% vs. 7%) and fluid retention (21% vs. 6%). The incidence of thromboembolic
      phenomena was comparable (8% vs. 5% in the Megestrol arm). Patients on the DES
      arm demonstrated a significantly greater median decrease in testosterone level.
      Correlation of the treatment arm assignment and the rate of tumor regression and
      the incidence of complete response revealed no significant difference between the
      arms. At 7 years, 16% of patients on the Megace arm and 21% of patients on the
      DES arm manifested evidence of local failure. CONCLUSIONS: The results of the
      study indicate comparable efficacy (using tumor clearance as an end point) of DES
      and Megestrol. Although DES appears more effective in suppressing testosterone,
      it is also associated with a higher incidence of drug-related toxicity.

PMID- 7721615
TI  - The rationale to switch from postoperative hyperfractionated accelerated
      radiotherapy to preoperative hyperfractionated accelerated radiotherapy in rectal
      cancer.
AB  - PURPOSE: To demonstrate the feasibility of preoperative Hyperfractionated
      Accelerated RadioTherapy (preop-HART) in rectal cancer and to explain the
      rationales to switch from postoperative HART to preoperative HART. METHODS AND
      MATERIALS: Fifty-two consecutive patients were introduced in successive Phase I
      trials since 1989. In trial 89-01, postoperative HART (48 Gy in 3 weeks) was
      applied in 20 patients. In nine patients with locally advanced rectal cancer,
      considered unresectable by the surgeon, 32 Gy in 2 weeks was applied prior to
      surgery (trial 89-02). Since 1991, 41.6 Gy in 2.5 weeks has been applied
      preoperatively to 23 patients with T3-T4 any N rectal cancer immediately followed
      by surgery (trial 91-01). All patients were irradiated at the department of
      radiation-oncology with a four-field box technique (1.6 Gy twice a day and with
      at least a 6-h interval between fractions). The minimal accelerating potential
      was 6 MV. Acute toxicity was scored according to the World Health Organization
      (WHO for skin and small bowel) and the Radiation Therapy Oncology Group criteria
      (RTOG for bladder). This was done weekly during treatment and every 3 months
      thereafter. Small bowel volume was estimated by a modified "Gallagher's" method.
      RESULTS: Acute toxicity was acceptable both in postoperative and preoperative
      setup. The mean acute toxicity was significantly lower in trial 91-01 compared to
      89-01. This difference was due to the smaller amount of small bowel in
      irradiation field and lower total dose in trial 91-01. Moreover, there was a
      significantly reduced delay between surgery and radiotherapy favoring trial 91-01
      (median delay 4 days compared to 46 days in trial 89-01). Nearly all patients in
      trial 89-02 and 91-01 underwent surgery (31 out of 32; 97%). Resection margins
      were negative in 29 out of 32. Hospitalization duration in trial 91-01 was not
      significantly different from trial 89-01 (19 vs. 21 days, respectively).
      CONCLUSIONS: Hyperfractionated accelerated radiotherapy immediately followed by
      surgery is feasible as far as acute toxicity is concerned. Preoperative HART is
      favored by a significantly lower acute toxicity related, in part, to a smaller
      amount of irradiated small bowel, and a shorter duration of the delay between
      radiotherapy and surgery. Moreover, the hospital stay after preoperative HART is
      not significantly increased.

PMID- 7721616
TI  - Preoperative infusional chemoradiation and surgery with or without an electron
      beam intraoperative boost for advanced primary rectal cancer.
AB  - PURPOSE: To compare the multimodality treatment results of surgical resection
      plus preoperative radiotherapy with concomitant protracted infusion chemotherapy
      (preop-chemoXRT), with or without an electron beam intraoperative radiotherapy
      (EB-IORT) boost, in 37 patients having advanced primary rectal cancer, with the
      results of a protocol using only preoperative radiotherapy (preop-XRT) plus
      surgical resection in a historic control group of 36 patients. METHODS AND
      MATERIALS: Thirty-eight patients with tethered T3 or T4 primary rectal cancer
      were treated with 45 Gy delivered in 25 fractions over 5 weeks plus infusional
      chemotherapy. Thirty-seven patients underwent surgical resection: 13 (35%) had
      restorative operations, and the remainder had either abdomino-perineal resection
      (APR) or pelvic exenteration (PE). Electron beam intraoperative radiotherapy (EB
      IORT) was used in doses of 10-20 Gy for 11 patients with adherent pelvic tumor.
      In the 36 historic control patients, the preop-XRT dose was 45 Gy, and 93% of
      them had APR or PE. RESULTS: The local recurrence rate was 3% for the preop
      chemoXRT group and 33% for the historic control group. The 3-year survival rate
      for patients treated with preop-chemoXRT plus resection was 82% compared with 62%
      for the historic control group. Distant metastases occurred more frequently in
      patients treated with an EB-IORT boost than in patients who were not (64% vs.
      19%, p < 0.05), and the overall 3-year survival rate was lower for the former
      (67% vs. 96%, p < 0.05). Acute and late toxicities were acceptable. CONCLUSIONS:
      Preop-chemoXRT for advanced primary rectal cancer results in better control of
      pelvic disease and better overall survival rates than does preop-XRT alone. With
      preop-chemoXRT, acute chemoradiation toxicity is increased whereas late morbidity
      is unchanged compared with preop-XRT alone. Local control in patients with areas
      of residual or clinically adherent disease is improved by the use of EB-IORT;
      however, patients treated with EB-IORT had poorer survival rates than those
      treated without EB-IORT.

PMID- 7721617
TI  - Linac radiosurgery for high-grade gliomas: the University of Florida experience.
AB  - PURPOSE: Stereotactic radiosurgery has been reported as a promising boost
      technique for the treatment of selected patients with high-grade glioma. The
      first 11 patients given this treatment at the University of Florida are reported.
      METHODS AND MATERIALS: Six patients with glioblastoma multiforme and five with
      anaplastic astrocytoma were carefully selected for treatment with linac
      radiosurgery. All patients had a Karnofsky performance status > or = 90%. Median
      age of patients was 42.1 years. External-beam radiotherapy delivered a median
      dose of 60 Gy. Stereotactic radiosurgery was delivered to the enhancing tumor
      volume without margin. Median treatment volume was 14 cm3 (equivalent sphere
      diameter, 3 cm). The maximum volume of any tumor treated was 22.5 cm3 (equivalent
      sphere diameter, 3.5 cm). Median stereotactic radiosurgery boost dose was 12.5
      Gy, and median prescription sphere was the 80% isodose shell. RESULTS: Despite
      rigorous selection and aggressive stereotactic boost irradiation, this patient
      cohort had a median actuarial survival of 17 months. All patients have had
      progression of intracranial disease within 1 year of radiosurgery, and only 3 of
      11 remain alive with a median follow-up of 13 months. CONCLUSION: These results
      differ significantly from others reported. Comparative analysis suggests tumor
      volume may be an important prognostic factor in patients treated with
      stereotactic radiosurgery. Future studies need to define appropriate patient
      cohorts for the boost technique.

PMID- 7721618
TI  - The value of nonuniform margins for six-field conformal irradiation of localized
      prostate cancer.
AB  - PURPOSE: Evaluate the hypothesis that by combining nonuniform margins with a
      technique for limiting the possible extent of posterior motion of the prostate
      during the delivery of six-field conformal radiotherapy (SFCRT) of the prostate,
      it is possible to adequately treat the clinical target volume (CTV) and minimize
      dose to normal structures. METHODS AND MATERIALS: Serial computed tomography (CT)
      scans of prostate patients were taken at 0.5 cm intervals for treatment planning
      purposes. The initial treatment planning scans were performed with the rectum
      empty and the bladder full. Subsequent scans were taken at the end of the first
      week of treatment with the bladder full, but with no attempt to empty the rectum,
      to mimic the typical treatment situation. The gross tumor volume (GTV),
      consisting of the prostate and seminal vesicles, as well as the CTV, were defined
      on the CT images with the aid of a urethrogram to define the inferior border
      (apex) of the prostate. Variable blocking margins were designed around the CTV
      using the University of Michigan three dimensional (3D) treatment planning system
      (UM-PLAN). Isodose distributions displayed on axial, sagittal, coronal, and
      oblique slices were used to evaluate the adequacy of the various margins applied.
      Nonuniform margins varying from 0.75 cm posteriorly to 2.0 cm anteriorly and
      inferiorly were compared to uniform margins of 1.0, 1.5, and 2.0 cm for each
      patient. Dose volume histograms (DVH) were used to compare doses to the GTV, CTV,
      rectum, and bladder. RESULTS: In a series of 10 patients scanned with the above
      protocol, treatment plans with nonuniform margins were compared with uniform
      margins of 1.0, 1.5, and 2.0 cm. Dose-volume histograms showed that nonuniform
      and 1.0 cm uniform margins deliver the lowest doses to the rectum and bladder,
      but the use of 1.0 cm uniform margins resulted in inadequate coverage of the CTV
      in 40% of the cases. The 1.5 and 2.0 cm uniform margins adequately covered the
      CTV but resulted in significantly higher doses to the bladder and rectum.
      CONCLUSIONS: The use of nonuniform margins, when combined with CT scans performed
      with the rectum empty and bladder full, can improve tumor control probability
      while minimizing the risk of morbidity to adjacent critical structures.

PMID- 7721619
TI  - A modified technique allowing interactive ultrasound-guided three-dimensional
      transperineal prostate implantation.
AB  - PURPOSE: Ultrasound-guided transperineal prostate implantation is a new technique
      for performing permanent isotope implants of the prostate. The details of the
      technique are presented to demonstrate its ability to place radioactive seeds
      three-dimensionally within the prostate gland to achieve uniform dose
      distribution without the need for complicated preplanning. METHODS AND MATERIALS:
      An accurate measurement of the prostate volume is made using biplanar transrectal
      ultrasound. The total activity to be implanted is derived from a look-up table
      based on prostate volume. The basic plan is to implant 60-70% of the total
      activity in the periphery of the gland and the remaining activity in the interior
      of the gland. The ultrasound transducer provides visualization of the prostate
      through transverse, longitudinal and oblique cuts and allows for accurate
      placement of implant needles, approximately 1 cm apart. In addition, these
      needles can be moved through the prostate under constant visualization, thus
      allowing for precise seed placement. RESULTS: The setup of the transrectal
      ultrasound device as well as prostate volume measurements are performed in 10 to
      15 min. The actual placement of the needles and seed implantation takes 1 to 1.5
      h to perform. Postimplantation dosimetric evaluation is performed using
      orthogonal x-ray films and 3 mm thick CT slices taken at 3 mm intervals. This
      evaluation has confirmed accurate seed placement within the prostate gland.
      CONCLUSION: Interactive ultrasound guided transperineal prostate implantation is
      a fast and accurate method of performing permanent radioactive isotope prostate
      implants.

PMID- 7721620
TI  - An evaluation of setup uncertainties for patients treated to pelvic sites.
AB  - PURPOSE: Successful delivery of conformal fields requires stringent
      immobilization and treatment verification, as well as knowledge of the setup
      reproducibility. The purpose of this study was to compare the three-dimensional
      distribution of setup variations for patients treated to pelvic sites with
      electronic portal imaging devices (EPID) and portal film. METHODS AND MATERIALS:
      Nine patients with genitourinary and gynecological cancers immobilized with
      custom casts and treated with a four-field whole-pelvis technique were imaged
      daily using an EPID and filmed once every five to seven treatments. The three
      dimensional translational and rotational setup errors were determined using a
      technique that relies on anatomical landmarks identified on simulation and
      treatment images. The distributions of the translational and rotational
      variations in each dimension as well as the total displacement of the treatment
      isocenter from the simulation isocenter were determined. RESULTS: Grouped
      analysis of all patients revealed average unidirectional translational deviations
      of less than 2 mm and a standard deviation of 5.3 mm. The average total
      undirected distance between the treatment and simulated isocenters was 8.3 mm
      with a standard deviation of 5 mm. Individual patient analysis revealed eight of
      nine patients had statistically significant nonzero mean translational variations
      (p < 0.05). Translational variations measured with film were an average of 1.4 mm
      less than those measured with EPID, but this difference was not statistically
      significant. CONCLUSION: Translational variations measured in this study are in
      general agreement with previous studies. The use of the EPID in this study was
      less intrusive and may have resulted in less additional attention being given
      each imaging setup. This may explain the slightly larger average translational
      variations observed with EPID vs. film, and suggests that the use of EPIDs is a
      superior method for assessing the true extent of setup displacements. Although no
      statistically significant translational variations for the patient group overall
      were observed, 90% of patients had significant translational variations in at
      least one direction when analyzed separately. The margin to be added to the
      clinical target volume (CTV) to account for setup uncertainties will depend on
      whether it is possible to identify patients with significant translational
      variations, and to eliminate these displacements from routine treatments. The
      choice to eliminate these variations and to use a smaller CTV margin will have to
      be accompanied by stringent frequent position verification methods and
      repositioning.

PMID- 7721621
TI  - Implications of tissue heterogeneity for radiosurgery in head and neck tumors.
AB  - PURPOSE: This study was undertaken to investigate the perturbation of small
      radiation beams by low density heterogeneities and to evaluate the ability of a
      Monte Carlo code to account for such perturbation. Performance of an inexpensive
      film scanning system was also evaluated. METHODS AND MATERIALS: Film and diode
      measurements were made in an acrylic phantom in which the size and position of an
      air gap were varied. Monte Carlo analysis was used to obtain additional
      verification of the measurements, to provide insight into photon and electron
      transport phenomena not directly measurable, and as a benchmark for the code.
      RESULTS: With 10 MV photons and a 1 cm circular field, a small 3-mm air cavity
      placed 2.6 cm deep in acrylic (full buildup) results in a reduction in central
      axis dose of 21% immediately following the cavity. Equilibrium is then
      reestablished over the next centimeter, after which the dose exceeds that of the
      homogeneous case by 3-4%. The loss in central axis equilibrium is highly field
      size dependent, with some loss occurring even for the largest (32 mm) collimator.
      In addition, the presence of the air cavity produces a significant increase in
      dose up to 2 cm lateral and outside the primary field. CONCLUSIONS: Tissue
      heterogeneities are not presently accounted for in radiosurgery calculations, yet
      have the ability to perturb dose significantly. Targets may potentially be
      underdosed, and adjacent critical structures overdosed. Inability to account for
      tissue heterogeneities may limit the use of the radiosurgery approach in some
      areas. A Monte Carlo approach may be the method of choice for small field dose
      calculation when tissue heterogeneities are encountered.

PMID- 7721622
TI  - Is the standardized helmet technique adequate for irradiation of the brain and
      the cranial meninges?
AB  - PURPOSE: To evaluate whether the standardized helmet technique is adequate to
      reliably cover the clinical target volume (whole brain including cranial
      meninges) during treatment planning and treatment delivery. METHODS AND
      MATERIALS: In 21 patients undergoing irradiation of the brain in acute
      lymphoblastic leukemia or primary cerebral lymphoma, the coverage of the clinical
      target volume was checked with a repeat computed tomography (CT) in the treatment
      position (head fixation with face mask). The accuracy of field alignment was
      quantitatively assessed with sequential verification films. For each patient,
      linear and rotational discrepancies were measured between the simulation and
      first check film, and between five consecutive verification films. RESULTS:
      Coverage of clinical target volume. In 11 cases (52%), the CT examinations showed
      that parts of the subfrontal region and midcranial fossa were not included by the
      field assigned under simulation. Accuracy of field alignment. For the total group
      of patients, all deviations were normally distributed with mean values between 
      1.2 mm and 1.5 mm and standard deviations of 2.9 mm to 3.7 mm for linear
      discrepancies, and 0.3 degrees +/- 3.2 degrees for rotational discrepancies. For
      all patients, deviations were similar for the transition from simulation to the
      treatment machine and for subsequent treatment delivery, with 50% and 95% of
      absolute differences being less than 2.0 mm and 6.5 mm, respectively. Maximum
      linear deviations were less than 9.5 mm. CONCLUSIONS: The currently used helmet
      technique is inadequate to cover the clinical target volume. Repeat CT
      examinations are a useful method to delineate the clinical target volume on an
      individual patient basis. In addition, statistical fluctuations of field
      displacements up to 1.0 cm have to be considered when prescribing safety margins
      for reliable coverage of the clinical target volume during treatment planning and
      delivery.

PMID- 7721623
TI  - A customized head and neck support system.
AB  - PURPOSE: To describe a customized head and neck immobilization system for
      patients receiving radiotherapy including a head support that conforms to the
      posterior contour of the head and neck. METHODS: The system includes a customized
      headrest to support the posterior head and neck. This is fixed to a thermoplastic
      face mask that molds to the anterior head/face contours. The shape of these
      customized head and neck supports were compared to "standard" supports. RESULTS:
      This system is comfortable for the patients and appears to be effective in
      reproducing the setup of the treatment. CONCLUSIONS: The variability in the size
      and shape of the customized posterior supports exceeded that of "standard"
      headrests. It is our clinical impression that the customized supports improve
      reproducibility and are now a standard part of our immobilization system. The
      quantitative analysis of the customized headrests and some commonly used
      "standard" headrests suggests that the customized supports are better able to
      address variabilities in patient shape.

PMID- 7721624
TI  - A prospective evaluation of thallium-201 single photon emission computerized
      tomography for brain tumor burden.
AB  - PURPOSE: The follow-up of patients with malignant brain tumors after surgery,
      radiation, and/or chemotherapy has been inadequate for evaluating brain tumor
      burden using computerized tomography (CT) or magnetic resonance imaging (MRI).
      Thallium-201 has been shown to concentrate in viable tumor, and Tl-201 single
      photon emission computerized tomography (SPECT) imaging can identify tumor burden
      more accurately than CT. METHODS AND MATERIALS: Thirty-one patients with
      glioblastoma and three patients with low grade astrocytoma were studied with Tl
      201 SPECT. Histololgic diagnosis was obtained in all patients by biopsy and all
      patients had CT scans within 2 weeks of the SPECT study. Seventeen patients were
      followed with one or more SPECT and CT evaluations. RESULTS: Single photon
      emission computerized tomography studies, after surgery, radiotherapy, and/or
      chemotherapy, were more accurate than CT in identifying progression or regression
      of disease. Twenty-three patients had evidence of disease and 11 patients had no
      evidence of recurrent disease in the initial Tl-201 SPECT study following
      therapy. Computerized tomography identified 20 of the 23 patients with disease
      and 6 of 11 patients with no recurrent disease. Follow-up with Tl-201 SPECT in 17
      patients suggested progression of disease in 9 patients, while CT showed
      progression in only 3 patients. Clinical examinations and repeat CT studies
      confirmed the accuracy of Tl-201 SPECT images. CONCLUSION: We found Tl-201 SPECT
      more accurate than CT scans in a prospective evaluation of 34 patients with brain
      tumor. Follow-up studies with both Tl-201 SPECT and CT imaging in 17 patients
      demonstrated that SPECT was more reliable than CT in identifying progression,
      improvement, or no change in brain tumor burden.

PMID- 7721625
TI  - Treatment planning structure and process in the United States: a "Patterns of
      Care" study.
AB  - PURPOSE: To conduct a study of the structure and process of treatment planning in
      the United States. METHODS AND MATERIALS: A Patterns of Care treatment planning
      consensus committee developed a survey form that was used to gather data for 106
      items relating to the structure and process of treatment planning. These
      questions were general in nature and not specific to any particular disease site.
      Seventy-three facilities were randomly selected for site visits from the 1321
      radiation therapy facilities in the United States: 21 academic, 26 hospital, and
      26 free-standing. During the site visit the facility physicist, assisted by the
      site-visit physicist, completed the form. RESULTS: Twenty-nine percent of
      facilities have cobalt-60 machines; 25% have 4 MV linacs; 75% have photon
      energies in the range of 5-8 MV; and less than 10% have energies greater than 20
      MV. Academic facilities led hospital and free-standing facilities by about 30
      percentage points in the availability of all electron energies (88 vs. 58%,
      approximately, in the range 4-13 MeV and scaling downward to about 60 vs. 30% at
      the highest energies). The national averages for the availability of Cs-137, Ir
      192, and I-125 were 87, 73, and 44%, respectively. Computerized tomography (CT)
      scanning is not available or not used in 15% of hospital and free-standing
      facilities. Ninety-six percent of facilities have treatment planning computers;
      at 10% of facilities physicians do not participate in treatment planning. The
      estimated national averages of facilities having formal quality assurance (QA)
      programs for treatment planning systems, simulators, film processors, and
      blocking systems are 44, 79, 62, and 55%, respectively. Sixty-three percent of
      facilities obtain independent machine calibrations. CONCLUSION: This is the first
      patterns of treatment planning study carried out in the United States and the
      results reported here will establish a baseline for future studies. The present
      study has identified some elements that were unexpected, such as the percentage
      of facilities lacking formal QA programs for treatment planning systems; however,
      it has not established any impact of such findings. It is recommended that future
      studies include the availability of new technologies such as multileaf
      collimation, dynamic wedges, digital portal imaging, and CT simulation. With the
      increasing nationwide concern with the cost of health care, we must continue to
      monitor the implementation, use, and impact on treatment outcome of new and
      expensive technologies.

PMID- 7721626
TI  - Radiation oncology crossword.

PMID- 7721627
TI  - Dose escalation by proton irradiation for adenocarcinoma of the prostate.

PMID- 7721628
TI  - A question-filled future for dose escalation in prostate cancer.

PMID- 7721629
TI  - Interferon gamma and thoracic irradiation in the treatment of unresectable stage
      IIIA/B non-small cell lung cancer.

PMID- 7721630
TI  - To boost or not to boost? ... it's not the only question! In response to Pezner,
      IJROBP 30:1251-1252; 1994.

PMID- 7721631
TI  - A practical partial transmission technique: regarding Weeks et al., IJROBP 30:693
      698; 1994.

PMID- 7721632
TI  - Response to total skin irradiation for mycosis fungoides associated with
      lymphomatoid papulosis: regarding Wilson et al., IJROBP 28:829-837; 1994.

PMID- 7721633
TI  - Extrapolating hypofractionated radiation schemes from radiosurgery data:
      regarding Hall et al., IJROBP 21:819-824; 1991 and Hall and Brenner, IJROBP
      25:381-385; 1993.

PMID- 7721634
TI  - Regarding Stelzer and Griffin, IJROBP 27:1057-1061; 1993. Oncology Working Group.

PMID- 7721635
TI  - What influences the incidence of complications in esophageal cancer treated with
      telebrachytherapy? Response to Kumar et al., IJROBP 27:1069-1072; 1993.

PMID- 7721636
TI  - Advanced prostate cancer: the results of a randomized comparative trial of high
      dose irradiation boosting with conformal protons compared with conventional dose
      irradiation using photons alone.
AB  - PURPOSE: Following a thorough Phase I/II study, we evaluated by a Phase III trial
      high versus conventional dose external beam irradiation as mono-therapy for
      patients with Stage T3-T4 prostate cancer. Patient outcome following standard
      dose radiotherapy or following a 12.5% increase in total dose to 75.6 Cobalt Gray
      Equivalent (CGE) using a conformal perineal proton boost was compared for local
      tumor control, disease-free survival, and overall survival. METHODS AND
      MATERIALS: Stage T3-T4, Nx, N0-2, M0 patients received 50.4 Gy by four-field
      photons and were randomized to receive either an additional 25.2 CGE by conformal
      protons (arm 1--the high dose arm, 103 patients, total dose 75.6 CGE) or an
      additional 16.8 Gy by photons (arm 2--the conventional dose arm, 99 patients,
      total dose 67.2 Gy). Actuarial overall survival (OS), disease-specific survival
      (DSS), total recurrence-free survival (TRFS), (clinically free, prostate specific
      antigen (PSA) less than 4ng/ml and a negative prostate rebiopsy, done in 38
      patients without evidence of disease) and local control (digital rectal exam and
      rebiopsy negative) were evaluated. RESULTS: The protocol completion rate was 90%
      for arm 1 and 97% for arm 2. With a median follow-up of 61 months (range 3 to 139
      months) 135 patients are alive and 67 have died, 20 from causes other than
      prostate cancer. We found no significant differences in OS, DSS, TRFS or local
      control between the two arms. Among those completing randomized treatment (93 in
      arm 1 and 96 in arm 2), the local control at 5 and 8 years for arm 1 is 92% and
      77%, respectively and is 80% and 60%, respectively for arm 2 (p = .089) and there
      are no significant differences in OS, DSS, and TRFS. The local control for the 57
      patients with poorly differentiated (Gleason 4 or 5 of 5) tumors at 5 and 8 years
      for arm 1 is 94% and 84% and is 64% and 19% on arm 2 (p = 0.0014). In patients
      whose digital rectal exam had normalized following treatment and underwent
      prostate rebiopsy there was a lower positive rebiopsy rate for arm 1 versus arm 2
      patients (28 vs. 45%) and also for those with well and moderately differentiated
      tumors versus poorly differentiated tumors (32 and 50%). These differences were
      not statistically significant. Grade 1 and 2 rectal bleeding is higher (32 vs.
      12%, p = 0.002) as may be urethral stricture (19 vs. 8%, p = 0.07) in the arm 1
      versus arm 2. CONCLUSIONS: An increase in prostate tumor dose by external beam of
      12.5% to 75.6 CGE by a conformal proton boost compared to a conventional dose of
      67.2 Gy by a photon boost significantly improved local control only in patients
      with poorly differentiated tumors. It has increased late radiation sequelae, and
      as yet, has not increased overall survival, disease-specific survival, or total
      recurrence-free survival in any subgroup. These results have led us to test by a
      subsequent Phase III trial the potential beneficial effect on local control and
      disease-specific survival of a 12.5% increase in total dose relative to
      conventional dose in patients with T1, T2a, and T2b tumors.

PMID- 7721637
TI  - Decreased sexual capacity after external radiation therapy for prostate cancer
      impairs quality of life.
AB  - PURPOSE: The aim of this study was to assess to what extent patients treated with
      radiation therapy for prostate cancer experience change in sexual functioning and
      to what extent this effects quality of life. METHODS AND MATERIALS: Information
      was provided by 53 men treated with radiation therapy for localized prostate
      cancer. Assessment was made with the "Radiumhemmets Scale of Sexual Functioning,"
      which measures sexual desire, erectile capacity, orgasm, and to what extent a
      decrease in any of these aspects of sexual functioning affects quality of life.
      Function before treatment was assessed retrospectively. RESULTS: Sexual desire
      diminished among 77% after treatment. The erection stiffness decreased in 77%.
      Before external radiation therapy, 66% had an erection usually sufficient for
      intercourse. Half of the men lost this ability after treatment. Of those
      retaining orgasm after treatment, 47% reported a decreased orgasmic pleasure and
      91% a reduced ejaculation volume. Of all men, 50% reported that quality of life
      had decreased much or very much due to a decline in the erectile capacity
      following external radiation therapy. CONCLUSION: The results of the present
      study indicate that external radiation therapy for prostate cancer is associated
      with a reduction in sexual desire, erectile capacity, and organism functions. In
      a majority of patients this reduces quality of life. Previously, we may have
      underestimated the importance an intact sexual function has for the quality of
      life in this patient category of elderly men.

PMID- 7721638
TI  - Adjuvant radiation therapy for rectal carcinoma: predictors of outcome.
AB  - PURPOSE: To review predictors of outcome, including sequencing of modalities and
      pretreatment findings for adjuvantly treated rectal cancer. METHODS AND
      MATERIALS: From 1975 through 1990, 307 patients with adenocarcinoma of the rectum
      underwent adjuvant radiation therapy. In 251 cases the radiation therapy was
      administered preoperatively, either 40-50 Gy (median dose 45 Gy) followed in 6-7
      weeks by surgery (210 cases), or 20 Gy in five fractions immediately prior to
      surgery (41 cases). In 56 cases, patients were referred postoperatively for
      radiation (median dose 50 Gy). Adjuvant chemotherapy was never given concurrently
      with the preoperative radiation (RT), although 43 of the cases (including 14 of
      the preoperative RT cases) received postoperative chemotherapy. RESULTS:
      Multivariate analysis (Cox model) indicated that significant predictors of better
      overall freedom from disease were preoperative rather than postoperative RT (p <
      0.001), low surgical stage (p < 0.0001), specialist surgeon (p = 0.007), low or
      moderate histologic grade (p = 0.026), and proximal lesion (p = 0.033). The
      significant predictors for better local control included use of preoperative RT
      (p < 0.001), low or moderate grade (p = 0.001), and low surgical stage (p =
      0.015). The 5-year local control and freedom from disease for the preoperative RT
      patients were 90% +/- 2% and 73% +/- 3%, respectively. The selected cases that
      received the short course of 20 Gy preoperatively did well. Although 24 out of 41
      patients proved to have Astler Coller B2 or C disease, local control at last
      follow-up was 39 out of 41 (95%). A second multivariate analysis of pretreatment
      factors was performed on the preoperative RT cases. The significant factors for
      both local control and overall freedom from disease were noncircumferential vs.
      circumferential tumor, proximal vs. distal lesion, and background of the surgeon.
      Additional negative factors on univariate analysis (although not achieving
      independent significance on multivariate analysis) included the finding of near
      obstructing lesions and elevated carcinoembryonic antigen (CEA). Grade > or = 3
      sequelae occurred in 8% of cases (including 3% bowel obstruction). The only
      significant factor for complications was background of the surgeon (4% for
      colorectal specialists vs. 12% for nonspecialists, p = 0.015). CONCLUSIONS:
      Significant factors for better tumor control included preoperative as opposed to
      postoperative RT and the experience of the surgeon. In selected cases, excellent
      results can be obtained with a short course of preoperative radiation. Concurrent
      chemotherapy need not be given routinely with preoperative radiation. Subgroups
      of preoperative RT cases at risk for distant metastases (who might benefit from
      postoperative chemotherapy), and at high risk for local failure (for whom
      concurrent preoperative chemotherapy and radiation might be considered), are
      identified.

PMID- 7721639
TI  - Radiation therapy quality control in a clinical trial of adjuvant postoperative
      treatment for rectal cancer.
AB  - PURPOSE: Deviations from protocol can detract from the reliability of results
      obtained in prospective clinical trials. In an effort to decrease the number of
      deviations in a prospective trial of adjuvant treatment for rectal cancer, we
      undertook pretreatment review of the irradiated fields. METHODS AND MATERIALS:
      Before initiation of radiation therapy, patients' radiation therapy fields were
      simulated by their radiation oncologists and films were submitted for review. The
      treating physicians were then informed whether their fields were in compliance
      with the protocol or whether any modifications were needed. RESULTS: Among the
      625 patients participating in this study who received radiation therapy as a
      component of protocol treatment, 419 (67%) had no radiation therapy deviations,
      127 (20%) had minor deviations, and 51 (8%) had major deviations; 28 (4%) could
      not be evaluated or did not receive protocol treatment because of circumstances
      beyond the treating radiation oncologist's control. The pretreatment quality
      control review identified major deviations in the radiation portals for 57 cases;
      these findings were communicated to the radiation oncologists prior to initiation
      of treatment, and, on final review, 40 had no deviation or only minor deviation.
      CONCLUSION: In the absence of pretreatment quality control review, 40 additional
      patients would have had major deviations from their radiation therapy protocol.
      On the basis of these findings, it is estimated that pretreatment quality control
      reduced the rate of major deviation from 15% to 8%. Pretreatment review of
      radiation therapy parameters is an effective method of reducing the frequency of
      major deviations in prospective clinical trials.

PMID- 7721640
TI  - Rectal cancer: the influence of tumor proliferation on response to preoperative
      irradiation.
AB  - PURPOSE: Regression of rectal carcinoma after preoperative irradiation is
      variable, likely reflecting differences in the physical and biologic properties
      of these tumors. This study examines the association between the pathologic
      response of rectal cancer after irradiation and its pretreatment proliferative
      state as assayed by the activity of the proliferative dependent antigens (Ki-67,
      PCNA) and mitotic counts. METHODS AND MATERIALS: One hundred and twenty-two
      patients with locally advanced rectal cancer received preoperative irradiation
      followed by surgery. Pretreatment tumor biopsies were scored for the extent of Ki
      67 and PCNA immunostaining and the number of mitoses per 10 high-powered fields.
      Postirradiation surgical specimens were examined for extent of residual disease.
      RESULTS: The tumors of 38 of 122 patients (31%) exhibited marked pathologic
      downstaging (no residual tumor or cancer confined to the rectal wall) after
      preoperative irradiation. Two features were associated with the likelihood of
      marked pathologic regression after preoperative irradiation: tumor proliferative
      activity and lesion size. When stratified by lesion size, marked tumor regression
      occurred most frequently in smaller tumors with high Ki-67, PCNA, and mitotic
      activity compared to larger tumors with lower Ki-67, PCNA, and mitotic activity.
      Intermediate downstaging rates were seen for small or large tumors with moderate
      Ki-67, PCNA, and mitotic activity. CONCLUSION: Tumor Ki-67, PCNA, and mitotic
      activity predicts the likelihood of response to irradiation, which may aid in
      formulating treatment policies for patients with rectal cancer.

PMID- 7721641
TI  - Femoral neck fracture following groin irradiation.
AB  - PURPOSE: The incidence and risk factors are evaluated for femoral neck fracture
      following groin irradiation for gynecologic malignancies. METHODS AND MATERIALS:
      The radiation therapy records of 1313 patients with advanced and recurrent cancer
      of the vagina, vulva, cervix, and endometrium, treated at the Mallinckrodt
      Institute of Radiology from 1954 to 1992, were reviewed. Median follow-up was
      12.7 years. From this group, 207 patients were identified who received
      irradiation to the pelvis and groins with anterposterior-posterior anterior (AP
      PA), 18 MV photons. Data were reviewed regarding irradiation dose to the femoral
      neck and other presumed risk factors including age, primary site, stage, groin
      node status, menopausal status, estrogen use, cigarette use, alcohol consumption,
      and osteoporosis. RESULTS: The per-patient incidence of femoral neck fracture was
      4.8% (10 out of 207). Four patients developed bilateral fractures. However, the
      cumulative actuarial incidence of fracture was 11% at 5 years and 15% at 10
      years. Cox multivariate analysis of age, weight, and irradiation dose showed that
      only irradiation dose may be important to developing fracture. Step-wise logistic
      regression of presumed prognostic factors revealed that only cigarette use and x
      ray evidence of osteoporosis prior to irradiation treatment were predictive of
      fracture. CONCLUSION: Femoral head fracture is a common complication of groin
      irradiation for gynecologic malignancies. Fracture in our database appears to be
      related to irradiation dose, cigarette use, and x-ray evidence of osteoporosis.
      Special attention should be given in treatment planning (i.e., shielding of
      femoral head/neck and use of appropriate electron beam energies for a portion of
      treatment) to reduce the incidence of this complication.

PMID- 7721642
TI  - Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine,
      lomustine, and vincristine for the treatment of anaplastic gliomas.
AB  - PURPOSE: To conduct a Phase II study to evaluate the long-term efficacy and
      safety of radiotherapy combined with intravenous bromodeoxyuridine for patients
      with anaplastic glioma tumors. METHODS AND MATERIALS: Between 1983 and 1987,
      study patients received 1.7-1.8 Gy radiation once a day, Monday through Friday,
      to a total dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for
      the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous
      infusion of bromodeoxyuridine at 0.8 g/m2/24 h; following radiotherapy, patients
      received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or
      until tumor progressed. RESULTS: One-hundred thirty eight patients (median age,
      43 years) were evaluable for analysis. Estimated 4-year survival for the
      anaplastic astrocytoma (AA) stratum (n = 116) is 46%. For the astrocytoma (ASTRO)
      stratum (n = 22), the 6-year survival is estimated at 79%. Estimated 4-year
      progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain
      irradiation was used in 23% and limited-field irradiation in 77%; patients
      receiving limited-field irradiation had a better survival rate (p = 0.07). Total
      tumor resection was performed in 15%, partial resection in 53%, and biopsy only
      in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have
      received additional treatment(s). For AA, fits of the Cox proportional hazards
      regression model showed that covariates individually predictive of survival were
      younger age (p < 0.001), Karnofsky performance score (p = 0.10). Major toxicities
      were rash during Weeks 1 through 6 requiring dose modification in 14%, Grade > or
      = III leukopenia in 18%, and Grade > or = III thrombocytopeni in 9%. CONCLUSION:
      The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with
      other published therapies, can improve progression-free survival, and aggressive
      treatment of ASTRO patients can lead to substantial increases in survival
      compared to published survival data.

PMID- 7721643
TI  - The effect of combining recombinant human tumor necrosis factor-alpha with local
      radiation on tumor control probability of a human glioblastoma multiforme
      xenograft in nude mice.
AB  - PURPOSE: To evaluate the antitumor activity of recombinant human tumor necrosis
      factor-alpha (rHuTNF-alpha) on a human glioblastoma multiforme (U87) xenograft in
      nude mice, and to study the effect of combining rHuTNF-alpha with local radiation
      on the tumor control probability of this tumor model. METHODS AND MATERIALS: U87
      xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8
      weeks old, male). When tumors reached a volume of about 110 mm3, mice were
      randomly assigned to treatment: rHuTNF-alpha alone compared with normal saline
      control; or local radiation plus rHuTNF-alpha vs. local radiation plus normal
      saline. Parameters of growth delay, volume doubling time, percentage of necrosis,
      and cell loss factor were used to assess the antitumor effects of rHuTNF-alpha on
      this tumor. The TCD50 (tumor control dose 50%) was used as an endpoint to
      determine the effect of combining rHuTNF-alpha with local radiation. RESULTS:
      Tumor growth in mice treated with a dose of 150 micrograms/kg body weight rHuTNF
      alpha, IP injection daily for 7 consecutive days, was delayed about 8 days
      compared to that in controls. Tumors in the treatment group had a significantly
      longer volume doubling time, and were smaller in volume and more necrotic than
      matched tumors in control group. rHuTNF-alpha also induced a 2.3 times increase
      of cell loss factor. The administration of the above-mentioned dose of rHuTNF
      alpha starting 24 h after single doses of localized irradiation under hypoxic
      condition, resulted in a significant reduction in TCD50 from the control value of
      60.9 Gy to 50.5 Gy (p < 0.01). CONCLUSION: rHuTNF-alpha exhibits an antitumor
      effect against U87 xenograft in nude mice, as evidenced by an increased delay in
      tumor growth as well as cell loss factor. Also, there was an augmentation of
      tumor curability when given in combination with radiotherapy, resulting in a
      significantly lower TCD50 value in the treatment vs. the control groups.

PMID- 7721644
TI  - In vivo radiation sensitivity of glioblastoma multiforme.
AB  - PURPOSE: Human glioblastoma (GBM) is one of the most resistant tumors to
      radiation. In previous reports, we have demonstrated a wide range of radiation
      sensitivity of GBM in vitro; that is, SF2 values of 0.2 to 0.8. The great
      sensitivity of some of the cell lines is not in accord with the almost invariably
      fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro
      pertains to cells cultured in optimal nutritional conditions. The TCD50 (the
      radiation dose necessary to control 50% of the tumors locally) determined in lab
      animals is analogous to the use of radiation with curative intent in clinical
      radiation oncology. The aim of the present study was (a) to evaluate the
      sensitivity of GBM in vivo relative to that of other tumor types and (b) assess
      the relationship between the single dose TCD50 of the xenografts and the
      sensitivity of the corresponding cell lines in vitro. METHODS AND MATERIALS: The
      TCD50 assay was used to study twelve human tumor lines. Four previously published
      values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft
      tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For
      further suppression of the residual immune system, all the animals received 6 Gy
      whole-body irradiation 1 day before transplantation. Local tumor irradiations
      were given as a single dose, under conditions of clamp hypoxia using a Cs
      irradiator. RESULTS: The TCD50 values for the 10 GBM xenografts varied between
      32.5 and 75.2 Gy, with an average of 47.2 +/- 13.1 Gy. The TCD50 values for the
      SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a
      mean of 46.8 +/- 6.4. The difference between the average TCD50 of GBM and SCC was
      not significant. The STS and CC xenografts had TCD50 values of 46.0 and 49.2 Gy,
      respectively. No correlation was found between the TCD50 in vivo and the SF2 or
      D0 in vitro. CONCLUSIONS: Our data on GBM xenografts showed a wide range of
      sensitivities to single dose irradiation in vivo, which does not correlate with
      the almost invariably fatal clinical outcome of these patients. No correlation
      was observed between the TCD50 in vivo and the in vitro SF2/D0 of the
      corresponding cell lines. Our in vivo and in vitro data on GBM suggest that
      radiation sensitivity alone does not explain the cause of the poor clinical
      response of GBM to radiation, and other factors could contribute to this
      response.

PMID- 7721645
TI  - Clinical research in allied health.
AB  - Allied health professionals in nutrition and medical dietetics, occupational
      therapy, physical therapy, and speech-language pathology and audiology play both
      unique and key cross-cutting roles in the furtherance of clinical research.
      Clinical research in nutrition and medical dietetics uniquely focuses on food
      nutrient intake and the metabolic utilization of nutrients. Clinical research in
      occupational therapy has a special focus on the relationship of impairment to
      disability, the adaptation to disability and the maximization of function.
      Physical therapy clinical research uniquely targets movement dysfunction and its
      evaluation and treatment within the context of quality and effective care.
      Clinical research in speech-language pathology and audiology is singular in its
      focus on deafness and hearing disorders, voice, speech, language and related
      disorders, and intersections among these and other neurological and physical
      conditions. Thus, all of these disciplines are making unique contributions to
      clinical research. Clinical research in these allied health professions is much
      more than the above specific foci. Inasmuch as these disciplines are rooted in
      practice, their contributions to research are inherently clinical. Many, if not
      most, of these contributions represent further validations of clinical practice
      or its underlying knowledge base. This means that, at a macro level, clinical
      research in allied health is very much "applied" research. Within allied health
      clinical research, this emphasis is redoubled at the "person," or individual
      level, where considerable attention is given to concepts of function and
      effectiveness. Clinical research in allied health has played a key cross-cutting
      role through its emphasis on collaboration. Possibly due to their professional
      maturation within multidisciplinary academic units, allied health professionals
      have demonstrated a level of comfort with multidisciplinary and interdisciplinary
      collaborations unique within many academic health science centers. While the
      above contributions are considerable, much more could be accomplished if
      identified barriers to career progression could be addressed. Principal barriers
      to the development of clinical research careers in allied health lie in the areas
      of training, mentoring, and funding. The lack of financial support for clinical
      research training is the major impediment. Progress in these areas, although
      valuable in itself, could also lead to more dedicated release time in clinical
      and academic settings, improved predoctoral and postdoctoral research training
      mechanisms, and better alignment of institutional and system reward structures
      with the clinical research mission. Within the existing constraints, allied
      health professionals have performed remarkably well in tapping into funding
      streams created for other disciplines and in establishing research traditions
      within relatively young health professions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7721646
TI  - Satisfaction, motivation, and commitment of senior medical record administration
      and medical technology students.
AB  - This study refined an existing Allied Health Career Attitude Scale (AHCAS) and
      measured the attitudes of a nationwide sample of students in medical record
      administration and medical technology. A survey of seniors enrolled in 35 medical
      record administration and 37 medical technology programs was conducted with 756
      usable student responses. The 39-item questionnaire was used to measure the
      satisfaction of seniors with their career choice, motivation to participate in
      professional organizations, and career outlook. On the total scale, scores of
      medical record administration students were significantly more positive. No
      significant difference was found between groups on the subscale measuring
      satisfaction with career choice. Medical record administration seniors were
      significantly more positive on the subscale measuring motivation to participate
      in professional organizations and the subscale measuring career outlook. The
      paper contains various interpretations of these findings with suggestions for the
      use of the scale by allied health educators.

PMID- 7721647
TI  - Interactive use of models of health-related behavior to promote interdisciplinary
      collaboration.
AB  - This pilot study examined the use of models of health-related behavior as foci
      for interaction to promote interdisciplinary collaboration among students
      enrolled in a graduate-level course at Washington University in St. Louis,
      Missouri. The course is one component of a master's program developed to meet the
      needs of health professionals whose goals are to participate in interdisciplinary
      roles in a variety of health care settings. Abilities requisite to the
      development of positive attitudes toward interdisciplinary collaboration include:
      (1) understanding of the functional roles of each discipline within the team; and
      (2) respect and value for each discipline's input in the decision-making process
      of the health team. Focused interaction was effective in increasing participants'
      understanding of the functional roles of each discipline at the .05 level of
      significance.

PMID- 7721648
TI  - Identification of core educational goals and related outcome measures for
      development of assessment programs in selected schools of allied health.
AB  - The purpose of this study was to determine important core educational goals and
      valid, feasible outcome measures to assess the goals in schools of allied health
      in academic health centers. The study also attempted to identify potential
      problems associated with using these outcome measures. The population included
      all allied health deans in public academic health centers accredited by the
      Southern Association of Colleges and Schools. Questionnaires with Likert scales
      were designed to gather opinions utilizing the Delphi technique. Deans identified
      13 important core educational goals and 84 outcome measures they perceived to be
      both valid and feasible to assess these goals. Outcome measures that require
      collection of highly objective data obtained from student or university records
      were considered most valid and feasible. Problems included inconsistency in
      definitions of outcomes, lack of appropriate methodology, and costs associated
      with developing instruments and collecting data. The results of this study
      indicate that there are a number of common educational goals and valid feasible
      outcome measures that schools can select to fit their unique needs, but potential
      problems must be addressed to ensure full and fair representation of the school's
      performance.

PMID- 7721649
TI  - Index of Graduate Theses and Projects in Allied Health.

PMID- 7721650
TI  - Distance consultation: concepts, components, and collaboration.
AB  - The economic environment forcing health care practitioners to do more with less
      is a pressing challenge for the isolated northern therapists and for the NOP.
      Retention rates will improve in the short-term, but the pressures on the
      survivors of cutbacks will be enormous. The demands on NOP resources will likely
      be changed dramatically both in terms of quantity and quality. Strategic planning
      is now a key component of all tasks. Models are currently under discussion that
      would facilitate the delivery of this service province-wide, and channel more
      funding into northern Ontario for the support of a network of multidisciplinary
      coordinators who could provide on-site support for sole charge therapists. The
      program described in this article is unique to Ontario and it is unlikely that it
      could be instituted in its entirety in another location. Many of its components,
      such as the establishment of regional support networks for new therapists,
      teleconferencing, and other methods of providing continuing education, are
      important elements for northern practitioners and could be adapted to other
      locations facing similar challenges. Evaluation of these components is an ongoing
      process which will be addressed in future papers.

PMID- 7721651
TI  - Archetypal foundations of addiction and recovery.
AB  - Addiction recovery takes place at an archetypal level. This is quite visible in
      the formulation of the twelve steps of AA which refer to forces in illness and
      recovery, e.g., a take-over by the addictive substances or process that renders
      one's life unmanageable and often devastated and the strong need to be in
      relation to a higher power for restoration of one's life. Many people respond to
      recovery programmes without getting into their individual psychology per se, but
      a number can benefit from analytic therapy which recognizes the archetypal level
      of psychic life. For those individuals analysis in conjunction with AA twelve
      step programmes can facilitate recovery, even as recovery facilitates analysis.

PMID- 7721652
TI  - Alcohol: a drug of dreams.
AB  - In this paper I have explored the way in which regressive phantasies of fusion
      may be brought into being by the heavy consumption of alcohol and the cerebral
      changes which result, which impair the individual's capacity to digest new
      information and experience; change therefore has to be resisted and loss and
      depressive anxiety cannot be experienced and worked through, hindering
      individuation. Two paradigms, one based on organic brain function and the other
      on psychodynamic understanding are brought together and shown not to be
      contradictory.

PMID- 7721653
TI  - Regulation of sperm motility: emerging evidence for a major role for protein
      phosphatases.

PMID- 7721654
TI  - Significant role of 5 alpha-reductase on feedback effects of androgen in rat
      anterior pituitary cells demonstrated with a nonsteroidal 5 alpha-reductase
      inhibitor ONO-3805.
AB  - A 5 alpha-reductase inhibitor with nonsteroidal structure, ONO-3805, has been
      used to study the role of 5 alpha-reductase on positive and negative feedback
      effects of androgen on gonadotropin secretion in the rat anterior pituitary
      gland. Initially, the potential of ONO-3805 to inhibit the formation of 5 alpha
      dihydrotestosterone (DHT) was evaluated. The activity of 5 alpha-reductase in rat
      anterior pituitary gland was approximately one-fourth of that in rat prostate
      gland or epididymis, with a Michaelis' constant (Km) value for testosterone of 5
      6 x 10(-7) M. When homogenates of rat anterior pituitary glands were incubated
      with 14C-testosterone (14C-T) in the presence of > or = 10(-7) M ONO-3805, the
      formation of labeled DHT and its metabolite 5 alpha-androstane-3 alpha,17 beta
      diol was inhibited by > 90%. The inhibition pattern was non-competitive, and the
      inhibition constant (Ki value) derived from Lineweaver-Burk plots was 3.9 x 10(
      11) M. Dispersed pituitary cells (1-2 x 10(5)/ml) were cultured for 48 hours and
      then further incubated with or without androgen and/or the inhibitor for 72 hours
      (basal secretion). After this incubation, the media were saved, and 10 nM of
      luteinizing hormone-releasing hormone (LH-RH) with the same concentration of
      androgen and/or the inhibitor as used in the 72-hour incubation was added to the
      cultures for 6 hours (LH-RH-induced secretion). Secreted follicle-stimulating
      hormone (FSH) and luteinizing hormone (LH) were assayed by radioimmunoassay
      (RIA). Both testosterone (T) and DHT stimulated 72-hour basal FSH secretion from
      cultured pituitary cells in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7721656
TI  - Testosterone regulation of proto-oncogene c-myc expression in primary Sertoli
      cell cultures from prepubertal rats.
AB  - The expression of c-myc has been associated with cell proliferation through
      changes of nuclear function. To evaluate the possibility that the proto-oncogene
      c-myc plays a role in testosterone-dependent gene regulation, the effects of
      testosterone on the expression of c-myc have been investigated in primary Sertoli
      cell cultures. Testosterone increased c-myc mRNA levels, with maximal stimulation
      reached in 16 hours. The induction of c-myc mRNA was dependent on the
      concentration of testosterone. Testosterone-induced c-myc mRNA levels were also
      increased in cells after addition of cycloheximide but reduced by actinomycin-D
      pretreatment. Even in the absence of hormone in culture medium, c-myc mRNA was
      clearly detectable in Sertoli cells from 8-day-old rats but hardly detectable in
      cells from 14 and 28 days of age. Testosterone stimulated c-myc mRNA expression
      in the Sertoli cells from only 8-/and 14-day-old rats. These results suggest that
      testosterone induces c-myc mRNA levels in the primary Sertoli cells from
      prepubertal rats, and then transient expression of c-myc may be responsible for
      some of the regulatory roles of testosterone-dependent genes in the Sertoli
      cells. The biological significance of testosterone-dependent c-myc induction is
      not known.

PMID- 7721657
TI  - Age-related decreased Leydig cell testosterone production in the brown Norway
      rat.
AB  - Previous studies have demonstrated that Leydig cell testosterone production
      diminishes with age in Brown Norway rats. The objective of the studies presented
      herein was to test the following possible explanations for age-related decline in
      steroidogenesis: (1) decline in Leydig cell number; (2) understimulation by
      luteinizing hormone (LH); (3) reduced ability of individual Leydig cells to
      produce testosterone; and (4) influence of loss of germ cells. Leydig cells
      isolated from the testes of young and aged rats by centrifugal elutriation and
      Percoll density gradient centrifugation were examined for their ability to
      produce testosterone when stimulated maximally with LH or with dibutyryl cyclic
      AMP (dbcAMP). Leydig cell number and volume were examined in situ using
      stereological methods. Serum LH levels were measured using a highly sensitive
      immunofluorometric assay. Average Leydig cell volume decreased with age, and
      consistent with this observation, individual Leydig cells isolated from aging
      rats produced significantly less testosterone than those from young rats whether
      the cells were cultured in vitro with maximally stimulating LH or with dbcAMP.
      The age-associated diminished testosterone production could not be explained by
      changes in Leydig cell number, serum LH levels, Leydig cell responsiveness to LH,
      or testicular germ cell content. These results, taken together, suggest that the
      reduced testosterone production seen in aged rats is related to defects in the
      steroidogenic pathway beyond the LH receptor-cAMP cascade. The nature of the
      initial age-related changes that cause reduced steroidogenesis is not known, and
      therefore it is not known whether such changes are intrinsic or extrinsic to the
      Leydig cells.

PMID- 7721658
TI  - Effects of macrophage depletion at different times after treatment with ethylene
      dimethane sulfonate (EDS) on the regeneration of Leydig cells in the adult rat.
AB  - Testicular macrophages were selectively depleted in the right testes of adult
      rats by an intratesticular injection of dichloromethylene diphosphonate
      containing liposomes (Cl2MDP-lp), whereas the left testes were injected with 0.9%
      NaCl and served as control. Before or after Leydig cell destruction with ethylene
      dimethane sulfonate (EDS), treatment with Cl2MDP-lp/NaCl was given at different
      times to study the requirements of macrophages in the different stages of Leydig
      cell regeneration. On day 30 after EDS treatment, new Leydig cells were abundant
      in the left, macrophage-containing testes. However, in the right, macrophage
      depleted testes, the number of Leydig cells was related to the time elapsed
      between EDS treatment and macrophage depletion. When macrophages were depleted on
      day 10 before or on days 4 or 10 after EDS treatment, new Leydig cells were
      nearly absent at 30 days. However, when macrophages were depleted on days 16 or
      22 after EDS treatment, Leydig cells were found at 30 days, but their numbers
      were equivalent to the number of Leydig cells that were already present in EDS
      treated animals at the time the macrophages were depleted. These results indicate
      that macrophages are needed for the differentiation of Leydig cells from
      mesenchymal precursors, as well as for the proliferative activity of the newly
      formed Leydig cells, possibly through the secretion of essential growth factors.

PMID- 7721655
TI  - Modulation of androgen receptor transcriptional activity by the estrogen
      receptor.
AB  - Estrogen/androgen receptor interactions in naturally occurring physiological
      systems and the effect of their respective steroid hormones on transcriptional
      activity remain undefined. In an attempt to delineate further the nature of the
      interaction between these two steroid hormone receptors we have examined the
      effect of cotransfection of androgen (AR) and estrogen receptor (ER) cDNAs on the
      expression of the mouse mammary tumor virus long terminal repeat region (MMTV
      LTR) linked to the chloramphenicol-acetyltransferase (CAT) reporter gene. In QT6
      cells, which contain neither AR nor ER, cotransfection of AR cDNA with the MMTV
      LTR-CAT reporter, resulted in transactivation only in the presence of
      dihydrotestosterone (DHT). Treatment with 10(-8) M each of estradiol-17 beta
      (E2), dexamethasone, or progesterone did not enhance CAT activity, whereas
      treatment with the androgens DHT and mibolerone resulted in 87% and 89% CAT
      activity. Transfection of increasing concentrations of ER cDNA in the presence of
      100 ng of AR cDNA and 10(-8) M each of DHT and E2 showed a dose-dependent
      decrease in CAT activity as compared to the response with DHT alone.
      Cotransfection of AR and ER cDNA in the presence of 10(-8) M DHT and increasing
      concentrations of E2 resulted in a dose-dependent decrease in CAT activity. When
      cells were treated with increasing concentrations of DHT with 10(-8) M E2 no
      significant increase in CAT activity was observed. In GC cells, which contain
      endogenous ER but no AR, cotransfection of AR cDNA and treatment with E2 and DHT,
      also reduced DHT-induced CAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721659
TI  - Effect of mesenchymal glandular inductors on the growth and cytodifferentiation
      of neonatal mouse seminal vesicle epithelium.
AB  - To investigate the developmental properties of glandular mesenchymal inductors
      along the cranial-caudal extent of the developing male urogenital tract, neonatal
      mouse seminal vesicle epithelium (SVE) was combined with mesenchyme of the
      seminal vesicle (SVM), urogenital sinus (UGM), bulbourethral gland (BUG-M), or
      bladder (BLM) and grafted under the renal capsule of adult syngeneic or athymic
      male mice. Both SVM + SVE and UGM + SVE tissue recombinants expressed SV
      histogenesis and SV secretory proteins. BUG-M + SVE recombinants exhibited
      extensive growth as evidenced by a 36-fold increase in wet weight and a 27-fold
      increase in DNA content; however, the glandular structures that were induced in
      the SVE lacked the convoluted mucosa typical of SV. Furthermore, neither SV nor
      prostatic secretory proteins were detected in these recombinants. SVE grown in
      association with BLM failed to develop altogether. Thus, the ability to promote
      SV histogenesis and function is distinctly different in mesenchyme of cranial
      (SVM and UGM) versus caudal (BUG-M) regions. This implies the existence of a
      glandular inductive field in the developing male urogenital tract within which
      inductive activity varies regionally.

PMID- 7721660
TI  - Measurement of immunoglobulin G levels in adult rat testicular interstitial fluid
      and serum.
AB  - Total immunoglobulin G (IgG) in rat testicular interstitial fluid and serum was
      measured by two-site enzyme-linked immunosorbent assay, which displayed minimal
      cross-reactivity with IgA or IgM. Normal adult testicular fluid IgG
      concentrations (2.67 +/- 0.98 mg/ml) were found to be 65% of the levels found in
      serum. Disruption of seminiferous tubule function by experimental cryptorchidism
      had no effect on either testicular or serum IgG concentrations. Castration also
      had no effect on serum IgG concentrations. The effect of the Leydig cell
      cytotoxin, ethane dimethane sulfonate, on IgG concentrations was obscured by the
      observation that dimethyl sulfoxide (the carrier solvent) itself effectively
      eliminated the IgG concentration gradient across the testicular microvasculature.
      In normal and cryptorchid rats, serum IgG and thymus weights showed no
      correlation with serum inhibin concentrations measured by radioimmunoassay,
      although thymus weights were significantly increased in castrate rats. The data
      confirm that the permeability of the rat testis to circulating IgG is relatively
      high compared with other tissues and suggest that the testicular transendothelial
      transfer of IgG is unaffected by changes in testicular activity or hormone
      secretion. The high intratesticular concentration of IgG and its apparent lack of
      local regulation provide further evidence that the phenomenon of immune privilege
      in this tissue cannot be attributed simply to restriction of immune effectors
      from the testicular environment. The data also indicate that serum IgG levels in
      the adult male rat are not influenced in the short-term by changes in peripheral
      testicular androgen levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721661
TI  - Coenzyme Q10 concentrations in normal and pathological human seminal fluid.
AB  - Coenzyme Q10 (CoQ10) levels were assayed in total seminal fluid or both in
      seminal fluid and seminal plasma in 77 subjects with normal or pathological
      findings at standard semen analysis. CoQ10 levels showed a significant
      correlation with sperm count and with sperm motility. An interesting exception
      was constituted by patients with varicocele, in whom the correlation with sperm
      concentration was preserved, whereas the correlation with sperm motility was
      lacking. Moreover, they showed an increased ratio of plasma CoQ to total seminal
      CoQ10 in comparison with the other subjects. These data suggest a
      pathophysiological meaning of CoQ10 in human seminal fluid and a possible
      molecular defect in varicocele patients. CoQ10 measurement could represent an
      important examination in infertile patients; moreover, from these results a
      rationale might arise for a possible treatment with exogenous CoQ10 in dyspermic
      patients.

PMID- 7721662
TI  - Two-dimensional electrophoretic profile of human sperm membrane proteins.
AB  - The purpose of this study was to characterize highly enriched human spermatozoa
      membrane proteins by two-dimensional electrophoresis and computer image analysis.
      Sperm membrane proteins were extracted by detergent solubilization from three
      different preparations: 1) washed semen cells following centrifugation and three
      wash steps in Ham's F-10 medium (the standard sperm preparation, which is
      contaminated with seminal immature germ cells, white blood cells, and acellular
      material), 2) the motile sperm fraction following centrifugation of diluted semen
      cells through a Percoll density gradient to enrich (> 98%) the viable mature
      sperm population, and 3) sperm membrane vesicles isolated from Percoll-purified
      motile mature sperm by nitrogen cavitation followed by differential
      centrifugation. The two-dimensional gel profiles of extracts of washed semen
      cells and motile spermatozoa contained more than 600 protein spots between pH 4
      and 7 and apparent molecular mass ranging from 7.9 to 93.5 kDa. Only 73% of the
      major proteins in these two samples matched by computer image analysis. The
      highly enriched sperm membrane vesicle extract showed a much simpler protein
      pattern, with only 64 major protein spots, 61 of which could be matched with
      proteins detected in extracts from purified motile sperm. The isoelectric point
      and molecular weight coordinates of these major human sperm membrane proteins
      could serve as a foundation for systematic isolation and further characterization
      of human sperm antigens for studies of mechanisms of fertilization and the
      development of contraceptive vaccines.

PMID- 7721663
TI  - The use of a seminal vesicle specific protein (MHS-5 antigen) for diagnosis of
      agenesis of vas deferens and seminal vesicles in azoospermic men.
AB  - Azoospermia is the cause of infertility in 8% of infertile male patients. Ten
      percent of those patients suffer from agenesis of the seminal vesicle (SV) and
      vas deferens (VD) agenesis. Currently, the diagnosis of SV and VD agenesis is
      based on low semen volume, low pH, and low fructose content of the seminal fluid
      of azoospermic men who have normal serum gonadotropins. In this study, an SV
      specific sperm-coating antigen, the MHS-5 antigen, was used as a marker for the
      presence of SVs. The SV-specific protein (SVSP), MHS-5, was present in the
      control group but was not found in any of the seven samples from azoospermic men
      with proven agenesis of SV and VD. Another semen component, the prostate-specific
      antigen (PSA), whose presence in the semen is not influenced by the SV and VD
      agenesis, was found in both the study and the control groups. Its presence ruled
      out the possibility of azoospermia due to ejaculatory duct obstruction. The
      absence of MHS-5 antigen in seminal fluid can be used as a tool for a reliable
      diagnosis of agenesis of SV and VD in azoospermic men.

PMID- 7721664
TI  - Effect of low-dose testicular irradiation on sperm count and fertility in
      patients with testicular seminoma.
AB  - The treatment of seminoma with radiation therapy risks transient infertility. We
      have prospectively followed eight patients with stage I seminoma of the testicle.
      All patients underwent radical orchiectomy of the affected testis. The mean age
      of the patients was 32.9 years (range 24-40). Each patient was treated with
      megavoltage radiation with a 10- or 18-MV linear accelerator. The remaining
      testicle was shielded using a standard lead enclosure, and the mean testicular
      dose was 44 cGy (range 20.8-78.2). Semen specimens were delivered to the lab
      within 30 minutes of ejaculation. All specimens were analyzed using a computer
      assisted sperm analyzer. Pretreatment parameters were within normal limits for
      all but one patient; one patient presented with a borderline normal sperm count
      at 18 and 22 x 10(6)/ml. Following treatment, there was a decrease in sperm
      count, detected at 3 months, to < 10 x 10(6)/ml (range 4.4- 8.6 x 10(6)) in all
      patients except one, who presented with an initial pretreatment count of 189 x
      10(6)/ml, which decreased to 58 x 10(6)/ml at 3 months, 32 x 10(6)/ml at 6
      months, and rose to 325 x 10(6)/ml by 12 months following treatment. Although the
      sperm count for this patient (D.L.) was within the normal range, the post
      radiation sperm count was less than 20% of the pretreatment count. There was no
      difference in the motility at 3 months, the mean of which was 51.3%. One
      patient's (F.C.) wife conceived at 9 months following treatment, one at 12 months
      (J.R.), and one (J.S.) at 14 months, and all have delivered normal
      infants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721665
TI  - Scrotal and oral temperatures are not related to semen quality of serum
      gonadotropin levels in spinal cord-injured men.
AB  - Scrotal temperature, oral temperature, and the difference between oral and
      scrotal temperature were measured in spinal cord-injured subjects (SCI) and non
      injured subjects as controls. We statistically correlated these measures to semen
      quality and serum gonadotropin levels in both groups. No difference was found
      between SCI and control subjects on any temperature measurement. Mean sperm
      motility, mean sperm morphology, and mean serum gonadotropin levels were
      significantly lower in SCI compared to control subjects, but these measures were
      not correlated to scrotal temperature, oral temperature, or the difference
      between oral and scrotal temperature in SCI or control subjects. These data
      indicate that: 1) there is not a generalized scrotal thermoregulatory dysfunction
      in SCI men; 2) scrotal temperature does not appear to contribute to poor semen
      quality in SCI men; and 3) elevated gonadotropin levels are not related to
      elevated scrotal temperatures in SCI men, as has been reported in non-injured,
      infertile men.

PMID- 7721666
TI  - Dual DNA staining assessment of bovine sperm viability using SYBR-14 and
      propidium iodide.
AB  - A new membrane-permeant DNA stain, SYBR-14, was used in combination with
      propidium iodide (PI) to estimate the proportion of living sperm in bovine semen.
      The SYBR-14 stained living sperm while PI only stained degenerate cells that had
      lost their membrane integrity. Staining with SYBR-14 resulted in the nuclei of
      living sperm fluorescing bright green. Aliquots containing nearly all living
      bovine sperm were prepared using glass wool/Sephadex filtration to remove dead
      and damaged cells. A portion of this filtered sample was killed by unprotected
      freeze-thawing and used to provide mixed aliquots containing known ratios of
      living and dead sperm. Flow cytometry was used to assess the green and red
      fluorescence of these mixtures. The percentages of living sperm, as determined by
      the log of green fluorescence, were 85.1, 68.8, 39.8, 20.7, and 1.4 for ratios of
      100:0, 75:25, 50:50, 25:75, and 0:100 of the filtered, killed mixtures. Also,
      bovine semen was diluted 1:60 in HEPES-0.1% bovine serum albumin and incubated
      for 0, 3, 6, and 24 hours at 36 degrees C to assess changes in cell viability. As
      cell death occurred during this incubation period, a relatively rapid transition
      of staining from green to red occurred as sperm died. Three replicates of
      cryopreserved sperm from six bulls were also examined using SYBR-14 and PI to
      assess the proportion of living and dead cells. Flow cytometric analyses of these
      samples, which had been processed and stored in homogenized milk, indicated that
      this stain combination was useful in assessing the quality of cryopreserved
      sperm. The combination of SYBR-14 and PI was determined to be an effective tool
      for assessing the viability of fresh or cryopreserved sperm.

PMID- 7721667
TI  - Annual meeting for operative andrologists, 1993. Dedicated to Alpay Kelami.

PMID- 7721668
TI  - Pregnancy obtained with human testicular spermatozoa in an in vitro fertilization
      program.
AB  - The fertilizing capacity of human testicular spermatozoa and the positive outcome
      of an in vitro fertilization program open a wide range of opportunities for men
      suffering from obstructive and inoperable azoospermia. In six cases, subzonal
      sperm injection or intracytoplasmic sperm injection techniques were applied to
      inject testicular spermatozoa into human oocytes. The fertilization rate after
      testicular sperm injection reached 45%. Normal cleavage was observed and
      replacement of 10 embryos in 6 patients resulted in one chemical and one ongoing
      pregnancy.

PMID- 7721669
TI  - A review of testicular intratubular germ cell neoplasia in infertile men.
AB  - A group of 2,739 infertile men whose testes were biopsied during the
      investigation of infertility in the period from January 1955 to December 1992
      have been reviewed. Unilateral intratubular germ cell neoplasia was seen in the
      testicular biopsies of 16 patients and was always associated with testicular
      atrophy (Johnsen score lower than 4). Germ cell tumors of the testis occurred in
      50% of untreated patients within 6 years and the longest period of tumor-free
      follow-up was 10 years. A retrospective study was performed to evaluate the
      incidence of tumors in a subset of 1,639 infertile men biopsied between 1955 and
      1982. Three of the patients, without intratubular germ cell neoplasia on the
      biopsy, were found to have developed a germ cell tumor. The incidence and
      management of intratubular germ cell neoplasia in infertile men is discussed.

PMID- 7721670
TI  - Seminal tract washout: a new diagnostic tool in complicated cases of male
      infertility.
AB  - The diagnosis of azoospermia or severe oligospermia that is made using
      conventional techniques (testicular biopsy, epididymal exploration, and
      vasovesiculography) may in some cases remain a dilemma. In such circumstances,
      post-testicular causes of obstruction must be evaluated. Following the clinical
      experience acquired in a selected population of 150 severely infertile subjects,
      the total sperm count in the fluid obtained from the bladder after a seminal
      tract washout during vasovesiculography has proved to be a valid tool to diagnose
      the location of the (sub-)obstruction in the seminal tract in complicated cases.
      Some representative cases are presented. In particular, seminal tract washout
      (STW) helps to identify functional distal seminal tract emptying disturbances and
      epididymal incomplete obstruction.

PMID- 7721671
TI  - In memoriam Alpay Kelami (1936-1992): his contributions to andrology.

PMID- 7721672
TI  - Function of human epididymal spermatozoa.
AB  - Human epididymal spermatozoa taken from caput, corpus, and cauda were
      investigated to determine their fertilizing capacity (22 epididymides from 11
      patients who had undergone orchidectomy because of prostatic cancer). The
      following functions, which have been reported to correlate positively with the
      fertilization rate, were determined: motility and progressive motility, chromatin
      condensation (assessed by aniline blue staining), acrosin activity, and induction
      of acrosome reaction by low temperature. In addition, stimulation of motility by
      pentoxifylline and phosphatidylcholine was examined. The results showed that
      motility, progressive motility, normal chromatin condensation, and inducible
      acrosome reaction increased from the caput to the cauda epididymidis, whereas
      acrosin activity was normal in all sections. Stimulation of progressive motility,
      especially that of caput spermatozoa, could be achieved by both pentoxifylline
      and phosphatidylcholine, the latter being definitely superior. In conclusion, our
      study confirmed that human spermatozoa in physiological status undergo several
      steps of maturation during the epididymal transit. Stimulation of sperm motility
      by phosphatidylcholine may be helpful for patients in whom epididymal spermatozoa
      are used for assisted reproduction.

PMID- 7721673
TI  - Hematospermia.
AB  - The appearance of blood in the seminal fluid is an alarming sign, with a rather
      inconstant origin. The causes of hematospermia are discussed based on a review of
      the literature and the authors' own experience with 84 patients. The importance
      of differential diagnosis is emphasized and a diagnostic scheme is presented.
      Therapeutic opportunities depending on etiology are discussed. It is concluded
      that although hematospermia is an often self-limiting sign, resolving in a few
      weeks, all patients should undergo a careful investigation to rule out the
      presence of malignancy or other significant disease.

PMID- 7721674
TI  - Comparison of different methods of treating varicocele.
AB  - Varicocele treatment was performed in 331 patients. One hundred fifteen patients
      were operated upon according to the technique of Bernardi (1947), 80 patients
      underwent occlusion of the testicular vein by detachable balloons, 47 patients
      were treated with percutaneous sclerotherapy, and 89 patients underwent
      laparoscopic varicocele treatment. The laparoscopic occlusion of the testicular
      vessels was done in two different ways: (1) coagulation of the testicular veins
      with electrocoagulating tweezers, and (2) occlusion of the suprainguinal
      testicular vessel with metal clips and transection of the vessels. Laparoscopic
      Group 1 showed a clearly higher complication rate and recurrence rate in
      comparison with the other methods, whereas in Group 2 we observed the best
      results with only 4% complications and recurrences. Because of its higher
      complication rate and recurrence rate, laparoscopic electrocoagulation of the
      testicular veins proved to be inadequate.

PMID- 7721675
TI  - Clinical outcome and cost comparison of percutaneous embolization and surgical
      ligation of varicocele.
AB  - We reviewed the records of 81 consecutive subfertile men with oligospermia and/or
      asthenospermia, treated for varicocele with either percutaneous embolization or
      surgical ligation between 1987 and 1991, and compared the outcomes and costs of
      the two procedures. All men had presented with infertility of at least 6 months
      duration, and in most cases female factors had been previously evaluated and
      treated. Patients were offered a choice of embolization or ligation of the
      internal spermatic vein. Forty-five men (56%) underwent ligation, and 36 men
      (44%) opted for embolization. The mean age, serum follicle-stimulating hormone,
      pretreatment sperm density, motility, and concentration of motile sperm were
      similar for the two groups. Seminal quality improved in 65% of all patients after
      varicocele ablation (46 of 71). Improvements were seen in postoperative sperm
      density (P < 0.01), motility (P < 0.002), and concentration of motile sperm (P <
      0.001). Thirty-nine percent of the assessable patients established pregnancies
      during the study interval (26 of 66). The two treatment groups did not differ
      significantly with regard to the likelihood of postoperative improvement in sperm
      density (P = 0.64), motility (P = 0.33), concentration of motile sperm (P =
      0.11), or pregnancy rate (P = 0.83). Percutaneous embolization and surgical
      ligation of varicocele are equally effective in improving male infertility and
      cost about the same. Embolization offers the potential advantage of shorter
      recovery to full activity as compared to surgical ligation. Where experienced
      interventional radiologists are available, percutaneous embolization should be
      offered as an alternative to open ligation.

PMID- 7721676
TI  - Is it useful to operate on adolescent patients affected by left varicocele?
AB  - In order to consider the possibility of avoiding seminal disorders induced by
      varicocele at puberty, we evaluated 200 patients who were operated on for left
      varicocele at adolescence. Seventy-five of our 200 adolescent patients had
      evaluations of seminal fluid prior to their varicocelectomy. Of these patients,
      75 were re-evaluated at the age of 21. In this latter group of patients, we
      observed 24 cases of hydrocele (32%) and 9 cases of varicocele recurrence (12%).
      These data were compared to 75 patients first presenting with a varicocele at 21
      25 years of age. If we exclude the cases with azoospermia, we observed the
      presence of altered seminal fluid in 35 (46.7%) of the operated at adolescence
      patients and in 42 (56%) of the adult patients with varicocele. These data
      support the hypothesis that operating on patients in adolescence may result in
      maintenance of fertility potential.

PMID- 7721677
TI  - Our experience with pharmacological erection treatment of erectile dysfunction.
AB  - Administration of vasoactive drugs intracavernously is a well-known easily used
      and inexpensive alternative in treatment of a certain group of patients with
      erectile dysfunction. There are a few drugs used for this purpose, but we prefer
      papaverine as the first choice because it is easily available and inexpensive in
      our country. We used alprostadil only in nonresponders to papaverine or if there
      was any complication with papaverine. We present a series of 69 patients, 24 with
      psychogenic (34.8%), 27 with organic (39.1%), and 18 (26.1) with mixed etiology
      of erectile dysfunction, treated with intracavernous self-injection therapy. Mean
      follow-up of the patients was 13.6 months (7-30 months). In this study, 3,430
      papaverine and 780 alprostadil injections were performed in 56 and 13 patients,
      respectively. In 75% of the papaverine injections and in 83% of the alprostadil
      injections, erections were achieved sufficient for sexual intercourse. During the
      follow-up, there were not any abnormal alterations in liver function tests. The
      main complaint of the patients who used papaverine was a burning sensation (98%)
      during administration of the drug, which did not last more than 1 minute. Of 13
      patients in the alprostadil group, 56.9% of the patients complained mainly of
      discomfort during erection. We concluded that intracavernous therapy is a good
      and inexpensive option in the management of erectile dysfunction in carefully
      selected patients.

PMID- 7721678
TI  - Combined intracavernous injection of papaverine and stimulation (CIS) test.
AB  - The inhibitory effect of the overactivity of the sympathetic nervous system that
      results from outpatient clinical conditions leads to poor erectile response to
      intracavernous injection of papaverine. The effects of self manual genital
      stimulation for improvement of erectile quality in insufficient papaverine
      response were investigated in 171 impotent men. Twenty-nine (63.04%) of 46
      patients who had a normal vascular system showed partial response to papaverine.
      Following self manual genital stimulation, full erection was achieved in all of
      them. Better erections were achieved in 28 of 42 patients with arterial disease.
      In patients subclassified as having slight, moderate, and severe arterial
      disease, improved erections were noted in 100%, 71.42%, and 64.28%, respectively.
      In the mixed vascular (arterial+venous) disease group (n = 46), the combined
      intracavernous injection of papaverine and stimulation (CIS) test led to a better
      erection in only 41.30%, whereas in the pure venogenic group (n = 37), this
      percentage was 66.66%. The inhibitory effect of the overactivity of the
      sympathetic nervous system is significantly reduced by the CIS test.

PMID- 7721679
TI  - Nesbit's procedure for penile curvature.
AB  - Between January 1982 and June 1992 83 patients with penile curvature due to
      Peyronie's disease or congenital curvature underwent a modified Nesbit's
      procedure for coital difficulties. This represented approximately 23% of the
      total number of patients referred to the male sexual dysfunction clinic with
      penile deformity. A confidential postal questionnaire was sent to all of the
      operated patients in order to determine the longterm results of surgery. Seventy
      eight of the 83 patients were contacted, aged 16-71 years (mean = 48 years).
      Sixty-two of the 78 (79%) were satisfied with the result of surgery and would be
      prepared to have the operation again. Twenty-two of the 78 were not having
      intercourse. As a result of this survey we have identified a group of people with
      initial satisfactory results who have since developed erectile failure. These
      have been offered either self injection therapy with a vasoactive agent or penile
      prostheses if they do not respond or do not wish to self inject.

PMID- 7721680
TI  - Evaluation of corpora alterations and erectile dysfunction following radical
      surgery for Peyronie's disease and long-term follow-up on 152 operated patients.
AB  - The radical surgical option we propose for Peyronie's disease consists in
      removing the sclerohyalinotic focus of disease and replacing it by an autologous
      dermal graft taken from the upper outer thigh area. Between 1981 and 1991, we
      operated on 335 patients with Peyronie's disease, 152 of whom underwent plaque
      excision and dermal graft. All could be assessed with a 2-year follow-up. Two
      main complications were observed: mild penile flexure due to scar retraction of
      the graft (35% of cases), and partial erectile deficit with decreased corporal
      rigidity (17% of cases). The degree of graft retraction is linked to the
      individual's histologic response. A mild deviation of the penis can occur some
      months after surgery and is not a relapse flexure due to disease progression, but
      is mere scar retraction and will spontaneously regress. Because the patient will
      date the onset of a postoperative erectile deficit from the time of the
      operation, it is advisable to assess preoperatively the erectile ability of all
      patients. Furthermore, an impaired erectile response could result from
      hypoaesthesia of the glans, postsurgical stress, and fibrosis of the erectile
      tissue. A retrospective assessment of radical surgery cases involving plaque
      excision and dermal graft led us to propose this option where precise indications
      apply, providing that other alterations of the erectile function are
      preoperatively assessed.

PMID- 7721681
TI  - Pregnancy with microsurgical vas sperm aspiration from a patient with neurologic
      ejaculatory dysfunction.
AB  - Patients with neurologic ejaculatory dysfunction who wish to have a child
      commonly undergo electroejaculation, which, unfortunately, may fail to stimulate
      either antegrade or retrograde ejaculation of sperm. Even when sperm are obtained
      with electroejaculation, conception still may not be achieved. We describe the
      achievement of a pregnancy after the intrauterine insemination of sperm obtained
      from microsurgical aspiration of the vas deferens. The intrauterine insemination
      of electroejaculated sperm had failed to achieve a pregnancy on three previous
      occasions. The relative merits of vas sperm aspiration and electroejaculation as
      part of the assisted reproduction regimen for men who have neurologic ejaculatory
      dysfunction are discussed.

PMID- 7721682
TI  - Our experience with penile deformations: incidence, operative techniques, and
      results.
AB  - Between the initiation of the "Penile Deformity Clinic" in 1988 in our Department
      of Urology, and the end of 1992, 1,862 males aged 0 (less than 24 hours old) to
      78 years old were examined. Five hundred of them were newborns, aged 0 to 5 days;
      they were examined to determine the incidence of congenital penile curvature. Two
      hundred and seventeen congenital curvatures were seen, and 102 of them were
      corrected surgically using four different corporoplasty techniques. From the 116
      Peyronie's Disease patients, 37 were treated surgically, either by corporoplasty
      or prosthesis implantation. From the 29 iatrogenic penile deformities, all the
      result of previous hypospadias repairs or urethroplasties for stricture repairs,
      18 needed surgical intervention, mostly for cosmetic reasons. Three congenital
      curvatures, corrected by plication, and one by Nesbit corporoplasty, recurred.
      Three other cases corrected by Nesbit corporoplasty reported temporary loss of
      glans sensation, and in a fourth one the sensory loss was permanent. It is our
      opinion that concentrating the care of these deformities in the hands of a small
      group of surgeons specialized in penile reconstructive surgery yields the best
      functional and esthetic results.

PMID- 7721683
TI  - ChrR positively regulates transcription of the Rhodobacter sphaeroides cytochrome
      c2 gene.
AB  - Transcription of the Rhodobacter sphaeroides cytochrome c2 gene (cycA) is
      negatively regulated by both the presence of oxygen and intermediates in
      tetrapyrrole biosynthesis. A mutation responsible for uncoupling cycA
      transcription from tetrapyrrole availability was localized to a gene (chrR) that
      encodes a 357-amino-acid protein. Analysis of a defined chrR null mutation
      indicated that this protein positively regulated cycA transcription. From this
      and other results, it appeared that the positive action of ChrR on cycA
      transcription is blocked by altering the availability of either heme or some
      intermediate in tetrapyrrole biosynthesis. A single missense mutation which
      substitutes an Arg for a Cys at residue 182 of ChrR (C182R) was shown to be
      necessary and sufficient for the increased cycA transcription seen in the mutant
      strain Chr4. Thus, it appears that this C182R substitution generated an altered
      function form of ChrR. In addition, by analyzing cycA transcription in delta ChrR
      strains, we showed that ChrR was not required for increased cycA transcription
      under anaerobic conditions. Instead, our results indicated that ChrR and the
      response regulator PrrA (J. M. Eraso and S. Kaplan, J. Bacteriol. 176:32-43,
      1994) functioned independently at the upstream cycA promoter that is activated
      under anaerobic conditions.

PMID- 7721684
TI  - Tn916 target DNA sequences bind the C-terminal domain of integrase protein with
      different affinities that correlate with transposon insertion frequency.
AB  - The conjugative transposon Tn916 inserts with widely different frequencies into a
      variety of target sites with related nucleotide sequences. The binding of
      chimeric proteins, consisting of maltose-binding protein fused to Tn916
      integrase, to three different target sequences for Tn916 was examined by DNase I
      protection experiments. The C-terminal DNA binding domain of the Tn916 integrase
      protein was shown to protect approximately 40 bp, spanning target sites in the
      orfA and cat genes of the plasmid pIP501 and in the cylA gene of the plasmid
      pAD1. Competition binding assays showed that the affinities of the three target
      sites for Tn916 integrase varied over a greater than 3- but less than 10-fold
      range and that the cat target site bound integrase at a lower affinity than did
      the other two target sites. A PCR-based assay for transposition in Escherichia
      coli was developed to assess the frequency with which a defective minitransposon
      inserted into each target site. In these experiments, integrase provided in trans
      from a plasmid was the sole transposon-encoded protein present. This assay
      detected transposition into the orfA and cylA target sites but not into the cat
      target site. Therefore, the frequency of transposon insertion into a particular
      target site correlated with the affinity of the target for the integrase protein.
      Sequences within the target fragments similar to known Tn916 insertion sites were
      not protected by integrase protein. Analysis ot he electrophoretic behavior of
      circularly permuted sets of DNA fragments showed that all three target sites
      contained structural features consistent with the presence of a static bend,
      suggesting that these structural features in addition to the primary nucleotide
      sequence are necessary for integrase binding and, thus, target site activity.

PMID- 7721685
TI  - Evidence for the presence of urease apoprotein complexes containing UreD, UreF,
      and UreG in cells that are competent for in vivo enzyme activation.
AB  - In vivo activation of Klebsiella aerogenes urease, a nickel-containing enzyme,
      requires the presence of functional UreD, UreF, and UreG accessory proteins and
      is further facilitated by UreE. These accessory proteins are proposed to be
      involved in metallocenter assembly (M. H. Lee, S. B. Mulrooney, M. J. Renner, Y.
      Markowicz, and R. P. Hausinger, J. Bacteriol. 174:4324-4330, 1992). A series of
      three UreD-urease apoprotein complexes are present in cells that express ureD at
      high levels, and these complexes are thought to be essential for in vivo
      activation of the enzyme (I.-S. Park, M. B. Carr, and R. P. Hausinger, Proc.
      Natl. Acad. Sci. USA 91:3233-3237, 1994). In this study, we describe the effect
      of accessory gene deletions on urease complex formation. The ureE, ureF, and ureG
      gene products were found not to be required for formation of the UreD-urease
      complexes; however, the complexes from the ureF deletion mutant exhibited delayed
      elution during size exclusion chromatography. Because these last complexes were
      of typical UreD-urease sizes according to native gel electrophoretic analysis, we
      propose that UreF alters the conformation of the UreD-urease complexes. The same
      studies revealed the presence of an additional series of urease apoprotein
      complexes present only in cells containing ureD, ureF, and ureG, along with the
      urease subunit genes. These new complexes were shown to contain urease, UreD,
      UreF, and UreG. We propose that the UreD-UreF-UreG-urease apoprotein complexes
      represent the activation-competent form of urease apoprotein in the cell.

PMID- 7721686
TI  - A promoter associated with the neisserial repeat can be used to transcribe the
      uvrB gene from Neisseria gonorrhoeae.
AB  - A recombinant plasmid capable of restoring UV resistance to an Escherichia coli
      uvrB mutant was isolated from a genomic library of Neisseria gonorrhoeae.
      Sequence analysis revealed an open reading frame whose deduced amino acid
      sequence displayed significant similarity to those of the UvrB proteins of E.
      coli, Micrococcus luteus, and Streptococcus pneumoniae. A gonococcal uvrB mutant
      was constructed and found to be extremely sensitive to UV radiation.
      Transcriptional fusions between portions of the gonococcal uvrB upstream region
      and a reporter gene were used to localize promoter activity, and the
      transcriptional start point of the gonococcal uvrB gene was mapped in E. coli by
      primer extension. A corresponding sigma 70 promoter was identified within a copy
      of the 26-bp neisserial repeat, and this identification provided the first
      evidence of a promoter associated with this repetitive element in N. gonorrhoeae.

PMID- 7721687
TI  - Bacterial adhesion to hydroxyl- and methyl-terminated alkanethiol self-assembled
      monolayers.
AB  - The attachment of bacteria to solid surfaces is influenced by substratum
      chemistry, but to determine the mechanistic basis of this relationship,
      homogeneous, well-defined substrata are required. Self-assembled monolayers
      (SAMs) were constructed from alkanethiols to produce a range of substrata with
      different exposed functional groups, i.e., methyl and hydroxyl groups and a
      series of mixtures of the two. Percentages of hydroxyl groups in the SAMs and
      substratum wettability were measured by X-ray photoelectron spectroscopy and
      contact angles of water and hexadecane, respectively. SAMs exhibited various
      substratum compositions and wettabilities, ranging from hydrophilic, hydroxyl
      terminated monolayers to hydrophobic, methyl-terminated monolayers. The kinetics
      of attachment of an estuarine bacterium to these surfaces in a laminar flow
      chamber were measured over periods of 120 min. The initial rate of net adhesion,
      the number of cells attached after 120 min, the percentage of attached cells that
      adsorbed or desorbed between successive measurements, and the residence times of
      attached cells were quantified by phase-contrast microscopy and digital image
      processing. The greatest numbers of attached cells occurred on hydrophobic
      surfaces, because (i) the initial rates of adhesion and the mean numbers of cells
      that attached after 120 min increased with the methyl content of the SAM and the
      contact angle of water and (ii) the percentage of cells that desorbed between
      successive measurements (ca. 2 min) decreased with increasing substratum
      hydrophobicity. With all surfaces, 60 to 80% of the cells that desorbed during
      the 120-min exposure period had residence times of less than 10 min, suggesting
      that establishment of firm adhesion occurred quickly on all of the test surfaces.

PMID- 7721688
TI  - Protein shift and antigenic variation in the S-layer of Campylobacter fetus
      subsp. venerealis during bovine infection accompanied by genomic rearrangement of
      sapA homologs.
AB  - Campylobacter fetus subsp. venerealis isolated from a case of human vaginosis was
      inoculated into the uterus of a C. fetus-negative heifer. Isolates obtained
      weekly from the vaginal mucus exhibited variations in high-molecular-mass-protein
      profiles from that of the original inoculum, which had a dominant 110-kDa S-layer
      protein. Immunoblots of the weekly isolates with monoclonal antibody probes
      against the 110-kDa S-layer protein and other C. fetus S-layer proteins
      demonstrated antigenic shifts. Genomic digests of the isolates probed with a 75
      mer oligonucleotide of the conserved sapA region also indicated that antigenic
      variation of the S-layer is accompanied by DNA rearrangement.

PMID- 7721689
TI  - Analysis of a novel gene and beta-galactosidase isozyme from a psychrotrophic
      Arthrobacter isolate.
AB  - We have characterized a new psychrotrophic Arthrobacter isolate which produces
      beta-galactosidase isozymes. When DNA from this isolate was transformed into an
      Escherichia coli host, we obtained three different fragments, designated 12, 14,
      and 15, each encoding a different beta-galactosidase isozyme. The beta
      galactosidase produced from fragment 12 was of special interest because the
      protein subunit was smaller (about 71 versus 116 kDa) than those typically
      encoded by the lacZ family. The isozyme encoded by fragment 12 was purified, and
      its activity and thermostability were examined. Although the enzyme is highly
      specific towards beta-D-galactoside substrates, its levels in the isolate do not
      increase in cells grown with lactose. Nucleotide sequence determination showed
      that the gene encoding isozyme 12 is not similar to the other members of the lacZ
      family but has regions similar to beta-galactosidase isozymes from Bacillus
      stearothermophilus and B. circulans. Addition of the isozyme 12 sequence to the
      database made it possible to examine these enzymes as possible members of a new,
      separate family. Our analysis of this new family showed some conserved amino
      acids corresponding to the lacZ acid-base catalytic region but no homology with
      the nucleophilic region. On the basis of these comparisons, we designated this a
      new lacG family.

PMID- 7721690
TI  - Mechanisms of biodegradation of metal-citrate complexes by Pseudomonas
      fluorescens.
AB  - Biodegradation of metal-citrate complexes by Pseudomonas fluorescens depends on
      the nature of the complex formed between the metal and citric acid. Bidentate
      Fe(III)-, Ni-, and Zn-citrate complexes were readily biodegraded, but the
      tridentate Cd- and Cu-citrate, and U-citrate complexes were not. The
      biodegradation of Ni- and Zn-citrate commenced after an initial lag period; the
      former showed only partial (70%) degradation, whereas the latter was completely
      degraded. Uptake studies with 14C-labeled citric acid and metal-citrate complexes
      showed that cells grown in medium containing citric acid transported free citric
      acid at the rate of 28 nmol min-1 and Fe(III)-citrate at the rate of 12.6 nmol
      min-1 but not Cd-, Cu-, Ni-, U-, and Zn-citrate complexes. However, cells grown
      in medium containing Ni- or Zn-citrate transported both Ni- and Zn-citrate,
      suggesting the involvement of a common, inducible transport factor. Cell extracts
      degraded Fe(III)-, Ni-, U-, and Zn-citrate complexes in the following order: The
      cell extract did not degrade Cd- or Cu-citrate complexes. These results show that
      the biodegradation of the U-citrate complex was limited by the lack of transport
      inside the cell and that the tridentate Cd- and Cu-citrate complexes were neither
      transported inside the cell nor metabolized by the bacterium.

PMID- 7721691
TI  - DNA-binding domain of the RepE initiator protein of mini-F plasmid: involvement
      of the carboxyl-terminal region.
AB  - The RepE initiator protein (251 residues) is essential for mini-F replication in
      Escherichia coli and exhibits two major functions: initiation of DNA replication
      from ori2 and autogenous repression of repE transcription. Whereas the initiation
      is mediated by RepE monomers that bind to the ori2 iterons (direct repeats), the
      autogenous repression is mediated by dimers that bind to the repE operator, which
      contains an inverted repeat sequence related to the iterons. We now report that
      the binding of RepE to these DNA sites is primarily determined by the C-terminal
      region of this protein. The mutant RepE proteins lacking either the N-terminal 33
      (or more) residues or the C-terminal 7 (or more) residues were first shown to be
      defective in binding to both the ori2 and the operator DNAs. However, direct
      screening and analysis of mutant RepEs which are specifically affected in binding
      to the ori2 iterons revealed that the mutations (mostly amino acid substitutions)
      occur exclusively in the C-terminal region (residues 168 to 242). These mutant
      proteins exhibited reduced binding to ori2 and no detectable binding to the
      operator. Thus, whereas truncation of either end of RepE can destroy the DNA
      binding activities, the C-terminal region appears to represent a primary DNA
      binding domain of RepE for both ori2 and the operator. Analogous DNA-binding
      domains seem to be conserved among the initiator proteins of certain related
      plasmids.

PMID- 7721692
TI  - Growth of Methanosarcina barkeri (Fusaro) under nonmethanogenic conditions by the
      fermentation of pyruvate to acetate: ATP synthesis via the mechanism of substrate
      level phosphorylation.
AB  - A mutant of Methanosarcina barkeri (Fusaro) is able to grow on pyruvate as the
      sole carbon and energy source. During growth, pyruvate is converted to CH4 and
      CO2, and about 1.5 mol of ATP per mol of CH4 is formed (A.-K. Bock, A. Prieger
      Kraft, and P. Schonheit, Arch. Microbiol. 161:33-46, 1994). The pyruvate
      utilizing mutant of M. barkeri could also grow on pyruvate when methanogenesis
      was completely inhibited by bromoethanesulfonate (BES). The mutant grew on
      pyruvate (80 mM) in the presence of 2 mM BES with a doubling time of about 30 h
      up to cell densities of about 400 mg (dry weight) of cells per liter. During
      growth on pyruvate, the major fermentation products were acetate and CO2 (about
      0.9 mol each per mol of pyruvate). Small amounts of acetoin, acetolactate,
      alanine, leucine, isoleucine, and valine were also detected. CH4 was not formed.
      The molar growth yield (Yacetate) was about 9 g of cells (dry weight) per mol of
      acetate, indicating an ATP yield of about 1 mol/mol of acetate formed. Growth on
      pyruvate in the presence of BES was limited; after six to eight generations, the
      doubling times increased and the final cell densities decreased. After 9 to 11
      generations, growth stopped completely. In the presence of BES, suspensions of
      pyruvate-grown cells fermented pyruvate to acetate, CO2, and H2. CH4 was not
      formed. Conversion of pyruvate to acetate, in the complete absence of
      methanogenesis, was coupled to ATP synthesis. Dicyclohexylcarbodiimide, an
      inhibitor of H(+)-translocating ATP synthase, did not inhibit ATP formation. In
      the presence of dicyclohexylcarbodiimide, stoichiometries of up to 0.9 mol of ATP
      per mol of acetate were observed. The uncoupler arsenate completely inhibited ATP
      synthesis, while the rates of acetate, CO2, and H2 formation were stimulated up
      to fourfold. Cell extracts of M. barkeri grown on pyruvate under nonmethenogenic
      conditions contained pyruvate: ferredoxin oxidoreductase (0.5 U/mg), phosphate
      acetyltransferase (12 U/mg), and acetate kinase (12 U/mg). From these data it is
      concluded that ATP was synthesized by substrate level phosphorylation during
      growth of the M. barkeri mutant on pyruvate in the absence of methanogenesis.
      This is the first report of growth of a methanogen under nonmethanogenic
      conditions at the expense of a fermentative energy metabolism.

PMID- 7721693
TI  - Uracil uptake in Escherichia coli K-12: isolation of uraA mutants and cloning of
      the gene.
AB  - Mutants defective in utilization of uracil at low concentrations have been
      isolated and characterized. The mutations in question (uraA) map close to the upp
      gene encoding uracil phosphoribosyltransferase. By complementation analysis, a
      plasmid that complements the uraA mutation has been isolated. The uraA gene was
      shown to be the second gene in a bicistronic operon with upp as the promoter
      proximal gene. The nucleotide sequence of the gene was determined, and the gene
      encodes a hydrophobic membrane protein with a calculated Mr of 45,030. The UraA
      protein has been identified in sodium dodecyl sulfate-polyacrylamide gels in the
      membrane fraction of minicells harboring the uraA plasmids.

PMID- 7721694
TI  - The Myxococcus xanthus asgA gene encodes a novel signal transduction protein
      required for multicellular development.
AB  - The Myxococcus xanthus asgA gene is one of three known genes necessary for the
      production of extracellular A-signal, a cell density signal required early in
      fruiting body development. We determined the DNA sequence of asgA. The deduced
      385-amino-acid sequence of AsgA was found to contain two domains: one homologous
      to the receiver domain of response regulators and the other homologous to the
      transmitter domain of histidine protein kinases. A kanamycin resistance (Kmr)
      gene was inserted at various positions within or near the asgA gene to determine
      the null phenotype. Those strains with the Kmr gene inserted upstream or
      downstream of asgA are able to form fruiting bodies, while strains containing the
      Kmr gene inserted within asgA fail to develop. The nature and location of the
      asgA476 mutation were determined. This mutation causes a leucine-to-proline
      substitution within a conserved stretch of hydrophobic residues in the N-terminal
      receiver domain. Cells containing the insertion within asgA and cells containing
      the asgA476 substitution have similar phenotypes with respect to development,
      colony color, and expression of an asg-dependent gene. An analysis of expression
      of a translational asgA-lacZ fusion confirms that asgA is expressed during growth
      and early development. Finally, we propose that AsgA functions within a signal
      transduction pathway that is required to sense starvation and to respond with the
      production of extracellular A-signal.

PMID- 7721695
TI  - Functional analysis of the phosphoprotein PII (glnB gene product) in the
      cyanobacterium Synechococcus sp. strain PCC 7942.
AB  - The PII protein (glnB gene product) in the cyanobacterium Synechococcus sp.
      strain PCC 7942 signals the cellular N status by being phosphorylated or
      dephosphorylated at a seryl residue. Here we show that the PII-modifying system
      responds to the activity of ammonium assimilation via the glutamine synthase
      glutamate synthase pathway and to the state of CO2 fixation. To identify possible
      functions of PII in this microorganism, a PII-deficient mutant was created and
      its general phenotype was characterized. The analysis shows that the PII protein
      interferes with the regulation of enzymes required for nitrogen assimilation,
      although ammonium repression is still detectable in the PII-deficient mutant. We
      suggest that the phosphorylation and dephosphorylation of PII are part of a
      complex signal transduction network involved in global nitrogen control in
      cyanobacteria. In this regulatory process, PII might be involved in mediating the
      tight coordination between carbon and nitrogen assimilation.

PMID- 7721696
TI  - Cloning, sequencing, and characterization of the gene encoding FrpB, a major iron
      regulated, outer membrane protein of Neisseria gonorrhoeae.
AB  - FrpB (for Fe-regulated protein B) is a 76-kDa outer membrane protein that is part
      of the iron regulon of Neisseria gonorrhoeae and Neisseria meningitidis. The frpB
      gene from gonococcal strain FA19 was cloned and sequenced. FrpB was homologous to
      several TonB-dependent outer membrane receptors of Escherichia coli as well as
      HemR of Yersinia enterocolitica and CopB of Moraxella catarrhalis. An omga
      insertion into the frpB coding sequence caused a 60% reduction in 55Fe uptake
      from heme, but careful analysis suggested that this effect was nonspecific. While
      FrpB was related to the family of TonB-dependent proteins, a function in iron
      uptake could not be documented.

PMID- 7721697
TI  - An Escherichia coli chromosomal ars operon homolog is functional in arsenic
      detoxification and is conserved in gram-negative bacteria.
AB  - Arsenic is a known toxic metalloid, whose trivalent and pentavalent ions can
      inhibit many biochemical processes. Operons which encode arsenic resistance have
      been found in multicopy plasmids from both gram-positive and gram-negative
      bacteria. The resistance mechanism is encoded from a single operon which
      typically consists of an arsenite ion-inducible repressor that regulates
      expression of an arsenate reductase and inner membrane-associated arsenite export
      system. Using a lacZ transcriptional gene fusion library, we have identified an
      Escherichia coli operon whose expression is induced by cellular exposure to
      sodium arsenite at concentrations as low as 5 micrograms/liter. This chromosomal
      operon was cloned, sequenced, and found to consist of three cistrons which we
      named arsR, arsB, and arsC because of their strong homology to plasmid-borne ars
      operons. Mutants in the chromosomal ars operon were found to be approximately 10-
      to 100-fold more sensitive to sodium arsenate and arsenite exposure than wild
      type E. coli, while wild-type E. coli that contained the operon cloned on a ColE1
      based plasmid was found to be at least 2- to 10-fold more resistant to sodium
      arsenate and arsenite. Moreover, Southern blotting and high-stringency
      hybridization of this operon with chromosomal DNAs from a number of bacterial
      species showed homologous sequences among members of the family
      Enterobacteriaceae, and hybridization was detectable even in Pseudomonas
      aeruginosa. These results suggest that the chromosomal ars operon may be the
      evolutionary precursor of the plasmid-borne operon, as a multicopy plasmid
      location would allow the operon to be amplified and its products to confer
      increased resistance to this toxic metalloid.

PMID- 7721698
TI  - Association of molybdopterin guanine dinucleotide with Escherichia coli dimethyl
      sulfoxide reductase: effect of tungstate and a mob mutation.
AB  - We have identified the organic component of the molybdenum cofactor in
      Escherichia coli dimethyl sulfoxide reductase (DmsABC) to be molybdopterin (MPT)
      guanine dinucleotide (MGD) and have studied the effects of tungstate and a mob
      mutation on cofactor (Mo-MGD) insertion. Tungstate severely inhibits anaerobic
      growth of E. coli on a glycerol-dimethyl sulfoxide minimal medium, and this
      inhibition is partially overcome by overexpression of DmsABC. Isolation and
      characterization of an oxidized derivative of MGD (form A) from DmsABC
      overexpressed in cells grown in the presence of molybdate or tungstate indicate
      that tungstate inhibits insertion of Mo-MGD. No electron paramagnetic resonance
      evidence for the assembly of tungsten into DmsABC was found between Eh = -450 mV
      and Eh = +200 mV. The E. coli mob locus is responsible for the addition of a
      guanine nucleotide to molybdo-MPT (Mo-MPT) to form Mo-MGD. DmsABC does not bind
      Mo-MPT or Mo-MGD in a mob mutant, indicating that nucleotide addition must
      precede cofactor insertion. No electron paramagnetic resonance evidence for the
      assembly of molybdenum into DmsABC in a mob mutant was found between Eh = -450 mV
      and Eh = +200 mV. These data support a model for Mo-MGD biosynthesis and assembly
      into DmsABC in which both metal chelation and nucleotide addition to MPT precede
      cofactor insertion.

PMID- 7721699
TI  - Complete DNA sequence, specific Tn5 insertion map, and gene assignment of the
      carotenoid biosynthesis pathway of Rhodobacter sphaeroides.
AB  - The carotenoid biosynthesis genes form a cluster within the genome of Rhodobacter
      sphaeroides, lying in the middle of a larger cluster and 45 kb in length, which
      contains genes for bacteriochlorophyll biosynthesis and for the reaction center
      and light-harvesting apoproteins. The positions and approximate limits of the
      carotenoid genes were determined previously by localized transposon Tn5
      mutagenesis and by comparison with the closely related Rhodobacter capsulatus
      carotenoid gene cluster. In this report, analysis of the DNA and deduced amino
      acid sequences of the carotenoid genes in R. sphaeroides are presented. Twenty
      five Tn5 insertion mutants were used to produce a base-specific Tn5 insertion map
      of this region, and carotenoid gene assignment was supported by spectroscopic,
      ultrastructural, and high-pressure liquid chromatography analyses of these
      mutants. A region in the 3' end of crtD which affects bacteriochlorophyll
      biosynthesis was discovered, and CrtA was found to possess a proline-rich C
      terminal region containing a repeated (Ala-Pro)n motif. CrtF also showed a high
      degree of sequence conservation with eukaryotic O-methyltransferases. This study
      provides gene sequences and assignments based upon a comprehensive structural,
      spectroscopic, and biochemical analysis of a range of carotenoid biosynthetic
      mutants; in each mutation, the point of Tn5 insertion is determined accurate to 1
      bp on the gene cluster.

PMID- 7721700
TI  - Identification and cloning of the gene encoding penicillin-binding protein 7 of
      Escherichia coli.
AB  - Penicillin-binding protein (PBP) 7 of Escherichia coli is a poorly characterized
      member of the family of enzymes that synthesize and modify the bacterial cell
      wall. The approximate chromosomal position of the gene encoding this protein was
      determined by measuring the expression of PBPs during lytic infection of E. coli
      by each of the 476 miniset members of the Kohara lambda phage genomic library.
      Phages lambda 363 and lambda 364, encompassing the region from 47.7 to 48 min of
      the chromosome, overproduced PBP 7. One open reading frame, yohB, was present on
      both these phages and directed the expression of PBPs 7 and 8. The predicted
      amino acid sequence of PBP 7 contains the consensus motifs associated with other
      PBPs and has a potential site near the carboxyl terminus where proteolysis by the
      OmpT protein could occur, creating an appropriately sized PBP 8. The PBP 7 gene
      (renamed pbpG) was interrupted by insertion of a kanamycin resistance gene
      cassette and was moved to the chromosome of E. coli. No obvious growth defects
      were observed, suggesting that PBP 7 is not essential for growth under normal
      laboratory conditions.

PMID- 7721701
TI  - Identification and sequence analysis of lpfABCDE, a putative fimbrial operon of
      Salmonella typhimurium.
AB  - A chromosomal region present in Salmonella typhimurium but absent from related
      species was identified by hybridization. A DNA probe originating from 78 min on
      the S. typhimurium chromosome hybridized with DNA from Salmonella enteritidis,
      Salmonella heidelberg, and Salmonella dublin but not with DNA from Salmonella
      typhi, Salmonella arizonae, Escherichia coli, and Shigella serotypes. Cloning and
      sequence analysis revealed that the corresponding region of the S. typhimurium
      chromosome encodes a fimbrial operon. Long fimbriae inserted at the poles of the
      bacterium were observed by electron microscopy when this fimbrial operon was
      introduced into a nonpiliated E. coli strain. The genes encoding these fimbriae
      were therefore termed lpfABCDE, for long polar fimbriae. Genetically, the lpf
      operon was found to be most closely related to the fim operon of S. typhimurium,
      both in gene order and in conservation of the deduced amino acid sequences.

PMID- 7721702
TI  - Structural study on the free lipid A isolated from lipopolysaccharide of
      Porphyromonas gingivalis.
AB  - The chemical structure of lipid A isolated from Porphyromonas gingivalis
      lipopolysaccharide was elucidated by compositional analysis, mass spectrometry,
      and nuclear magnetic resonance spectroscopy. The hydrophilic backbone of free
      lipid A was found to consisted of beta(1,6)-linked D-glucosamine disaccharide 1
      phosphate. (R)-3-Hydroxy-15-methylhexadecanoic acid and (R)-3-hydroxyhexadecanoic
      acid are attached at positions 2 and 3 of the reducing terminal residue,
      respectively, and positions 2' and 3' of the nonreducing terminal unit are
      acylated with (R)-3-O-(hexadecanoyl)-15-methylhexadecanoic acid and (R)-3-hydroxy
      13-methyltetradecanoic acid, respectively. The hydroxyl group at position 4' is
      partially replaced by another phosphate group, and the hydroxyl groups at
      positions 4 and 6' are unsubstituted. Considerable heterogeneity in the fatty
      acid chain length and the degree of acylation and phosphorylation was detected by
      liquid secondary ion-mass spectrometry (LSI-MS). A significant pseudomolecular
      ion of lipid A at m/z 1,769.6 [M-H]- corresponding to a diphosphorylated GlcN
      backbone bearing five acyl groups described above was detected in the negative
      mode of LSI-MS. Predominant ions, however, were observed at m/z 1,434.9 [M-H]-
      and m/z 1,449.0 [M-H]-, each representing monophosphoryl lipid A lacking (R)-3
      hydroxyhexadecanoic and (R)-3-hydroxy-13-methyltetradecanoic acids, respectively.
      The presence of mono- and diphosphorylated lipid A species was also confirmed by
      LSI-MS of de-O-acylated lipid A (m/z 955.3 and 1,035.2, respectively).

PMID- 7721703
TI  - Genetic analysis of a region of the Enterococcus faecalis plasmid pCF10 involved
      in positive regulation of conjugative transfer functions.
AB  - The prgB gene encodes the surface protein Asc10, which mediates cell aggregation
      resulting in high-frequency conjugative transfer of the pheromone-inducible
      tetracycline resistance plasmid pCF10 in Enterococcus faecalis. Previous Tn5
      insertional mutagenesis and sequencing analysis of a 12-kb fragment of pCF10
      indicated that a region containing prgX, -Q, -R, -S, and -T, located 3 to 6 kb
      upstream of prgB, is required to activate the expression of prgB. Complementation
      studies showed that the positive regulatory region functions in cis in an
      orientation-dependent manner (J. W. Chung and G. M. Dunny, Proc. Natl. Acad. Sci.
      USA 89:9020-9024, 1992). In order to determine the involvement of each gene in
      the activation of prgB, Tn5 insertional mutagenesis and exonuclease III deletion
      analyses of the regulatory region were carried out. The results indicate that
      prgQ and -S are required for the expression of prgB, while prgX, -R, and -T are
      not required. Western blot (immunoblot) analysis of these mutants shows that prgQ
      is also essential for the expression of prgA (encoding the surface exclusion
      protein Sec10), which is located between prgB and the positive-control region.
      Complementation analysis demonstrates that a cis-acting regulatory element is
      located in the prgQ region and that pCF10 sequences in an untranslated region 3'
      from prgQ are an essential component of the positive-control system. Analyses of
      various Tn5 insertions in pCF10 genes suggest that transcription reading into
      this transposon is terminated in E. faecalis but that outward-reading transcripts
      may initiate from within the ends of Tn5 or from the junction sequences.

PMID- 7721704
TI  - The genes involved in production of and immunity to sakacin A, a bacteriocin from
      Lactobacillus sake Lb706.
AB  - Sakacin A is a small, heat-stable, antilisterial bacteriocin produced by
      Lactobacillus sake Lb706. The nucleotide sequence of a 8,668-bp fragment, shown
      to contain all information necessary for sakacin A production and immunity, was
      determined. The sequence revealed the presence of two divergently transcribed
      operons. The first encompassed the structural gene sapA (previously designated
      sakA) and saiA, which encoded a putative peptide of 90 amino acid residues. The
      second encompassed sapK (previously designated sakB), sapR, sapT, and sapE. sapK
      and sapR presumably encoded a histidine kinase and a response regulator with
      marked similarities to the AgrB/AgrA type of two-component signal-transducing
      systems. The putative SapT and SapE proteins shared similarity with the
      Escherichia coli hemolysin A-like signal sequence-independent transport systems.
      SapT was the HlyB analog with homology to bacterial ATP-binding cassette
      exporters implicated in bacteriocin transport. Frameshift mutations and deletion
      analyses showed that sapK and sapR were necessary for both production and
      immunity, whereas sapT and sapE were necessary for production but not for
      immunity. The putative SaiA peptide was shown to be involved in the immunity to
      sakacin A. The region between the operons contained IS1163, a recently described
      L. sake insertion element. IS1163 did not appear to be involved in expression of
      the sap genes. Northern (RNA) blot analysis revealed that the putative SapK/SapR
      system probably acts as a transcriptional activator on both operons. A 35-bp
      sequence, present upstream of the putative sapA promoter, and a similar sequence
      (30 of 35 nucleotides identical) upstream of sapK were shown to be necessary for
      proper expression and could thus be possible targets for transcriptional
      activation.

PMID- 7721705
TI  - Purification of 1,3-propanediol dehydrogenase from Citrobacter freundii and
      cloning, sequencing, and overexpression of the corresponding gene in Escherichia
      coli.
AB  - 1,3-Propanediol dehydrogenase (EC 1.1.1.202) was purified to homogeneity from
      Citrobacter freundii grown anaerobically on glycerol in continuous culture. The
      enzyme is an octamer of a polypeptide of 43,400 Da. When tested as a
      dehydrogenase, the enzyme was most active with substrates containing two primary
      alcohol groups separated by one or two carbon atoms. In the physiological
      direction, 3-hydroxypropionaldehyde was the preferred substrate. The apparent Km
      values of the enzyme for 3-hydroxypropionaldehyde and NADH were 140 and 33
      microM, respectively. The enzyme was inhibited by chelators of divalent cations
      but could be reactivated by the addition of Fe2+. The dhaT gene, encoding the 1,3
      propanediol dehydrogenase, was cloned, and its nucleotide sequence (1,164 bp) was
      determined. The deduced dhaT gene product (387 amino acids, 41,324 Da) showed a
      high level of similarity to a novel family (type III) of alcohol dehydrogenases.
      The dhaT gene was overexpressed in Escherichia coli 274-fold by using the T7 RNA
      polymerase/promoter system.

PMID- 7721706
TI  - Carbon monoxide-induced activation of gene expression in Rhodospirillum rubrum
      requires the product of cooA, a member of the cyclic AMP receptor protein family
      of transcriptional regulators.
AB  - Induction of the CO-oxidizing system of the photosynthetic bacterium
      Rhodospirillum rubrum is regulated at the level of gene expression by the
      presence of CO. In this paper, we describe the identification of a gene that is
      required for CO-induced gene expression. An 11-kb deletion of the region adjacent
      to the previously characterized cooFSCTJ region resulted in a mutant unable to
      synthesize CO dehydrogenase in response to CO and unable to grow utilizing CO as
      an energy source. A 2.5-kb region that corresponded to a portion of the deleted
      region complemented this mutant for its CO regulation defect, restoring its
      ability to grow utilizing CO as an energy source. When the 2.5-kb region was
      sequenced, one open reading frame, designated cooA, predicted a product showing
      similarity to members of the cyclic AMP receptor protein (CRP) family of
      transcriptional regulators. The product, CooA, is 28% identical (51% similar) to
      CRP and 18% identical (45% similar) to FNR from Escherichia coli. The insertion
      of a drug resistance cassette into cooA resulted in a mutant that could not grow
      utilizing CO as an energy source. CooA contains a number of cysteine residues
      substituted at, or adjacent to, positions that correspond to residues that
      contact cyclic AMP in the crystal structure of CRP. A model based on this
      observation is proposed for the recognition of CO by Cooa. Adjacent to cooA are
      two genes, nadB and nadC, with predicted products similar to proteins in other
      bacteria that catalyze reactions in the de novo synthesis of NAD.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7721707
TI  - The hyperthermophilic archaeon Pyrodictium occultum has two alpha-like DNA
      polymerases.
AB  - We cloned two genes encoding DNA polymerases from the hyperthermophilic archaeon
      Pyrodictium occultum. The deduced primary structures of the two gene products
      have several amino acid sequences which are conserved in the alpha-like (family
      B) DNA polymerases. Both genes were expressed in Escherichia coli, and highly
      purified gene products, DNA polymerases I and II (pol I and pol II), were
      biochemically characterized. Both DNA polymerase activities were heat stable, but
      only pol II was sensitive to aphidicolin. Both pol I and pol II have associated
      5'-->3' and 3'-->5' exonuclease activities. In addition, these DNA polymerases
      have higher affinity to single-primed single-stranded DNA than to activated DNA;
      even their primer extension abilities by themselves were very weak. A comparison
      of the complete amino acid sequences of pol I and pol II with two alpha-like DNA
      polymerases from yeast cells showed that both pol I and pol II were more similar
      to yeast DNA polymerase III (ypol III) than to yeast DNA polymerase II (ypol II),
      in particular in the regions from exo II to exo III and from motif A to motif C.
      However, comparisons region by region of each polymerase showed that pol I was
      similar to ypol II and pol II was similar to ypol III from motif C to the C
      terminus. In contrast, pol I and pol II were similar to ypol III and ypol II,
      respectively, in the region from exo III to motif A. These findings suggest that
      both enzymes from P. occultum play a role in the replication of the genomic DNA
      of this organism and, furthermore, that the study of DNA replication in this
      thermophilic archaeon may lead to an understanding of the prototypical mechanism
      of eukaryotic DNA replication.

PMID- 7721708
TI  - Similarity of "core" structures in two different glycans of tyrosine-linked
      eubacterial S-layer glycoproteins.
AB  - Previously, the repeating-unit structure of the S-layer glycoprotein from the
      eubacterium Bacillus alvei CCM 2051 has been determined to be [-->3)-beta-D-Galp
      (1-->4)-[alpha-D-Glcp-(1-->6)-]-beta-D-ManpNAc- (1-->]n (E. Altman, J.-R.
      Brisson, P. Messner, and U. B. Sleytr, Biochem. Cell Biol. 69:72-78, 1991).
      Nuclear magnetic resonance spectroscopic reexamination of this glycan reveals
      that the O-antigen-like domain of the polysaccharide is [see text] connected with
      the S-layer polypeptide through the "core" structure -->3)-alpha-L-Rhap-(1-->3)
      alpha-L-Rhap-(1-->3)-alpha-L-R hap-(1-->3)-beta-D-Galp-(1-->O)-Tyr. Except for
      the substitution in position 4 of the nonreducing rhamnose with the modified
      glyceric acid phosphate residue GroA-2-->OPO2-->4-beta-D-ManpNAc-(1-->, this core
      is identical to the core of the tyrosine-linked glycan from the S-layer
      glycoprotein of Thermoanaerobacter thermohydrosulfuricus L111-69 (K. Bock, J.
      Schuster-Kolbe, E. Altman, G. Allmaier, B. Stahl, R. Christian, U. B. Sleytr, and
      P. Messner, J. Biol. Chem. 269:7137-7144, 1994).

PMID- 7721709
TI  - Cross-species complementation of the indispensable Escherichia coli era gene
      highlights amino acid regions essential for activity.
AB  - Era is an essential GTP binding protein in Escherichia coli. Two homologs of this
      protein, Sgp from Streptococcus mutans and Era from Coxiella burnetii, can
      substitute for the essential function of Era in E. coli. Site-specific and
      randomly generated Era mutants which may indicate regions of the protein that are
      of functional importance are described.

PMID- 7721711
TI  - Transformation of carbon tetrachloride via sulfur and oxygen substitution by
      Pseudomonas sp. strain KC.
AB  - Pseudomonas sp. strain KC transforms carbon tetrachloride into carbon dioxide and
      nonvolatile products, without chloroform as an intermediate. To define the
      pathway for hydrolysis, nonvolatile products were analyzed. Condensation products
      containing the carbon atom of carbon tetrachloride as carbonyl and thioxo
      moieties were identified, indicating the intermediacy of phosgene and
      thiophosgene in the pathway.

PMID- 7721710
TI  - Molecular characterization of the gene cluster coxMSL encoding the molybdenum
      containing carbon monoxide dehydrogenase of Oligotropha carboxidovorans.
AB  - The CO dehydrogenase structural genes (cox) and orf4 are clustered in the
      transcriptional order coxM--> coxS--> coxL--> orf4 on the 128-kb megaplasmid
      pHCG3 of the carboxidotroph Oligotropha carboxidovorans OM5. Sequence analysis
      suggested association of molybdopterin cytosine dinucleotide and flavin adenine
      dinucleotide with CoxL and of the [2Fe-2S] clusters with CoxS.

PMID- 7721712
TI  - A stationary-phase-dependent viability block governed by two different
      polypeptides from the RhsA genetic element of Escherichia coli K-12.
AB  - Multicopy plasmids bearing a small internal portion of the RhsA genetic element
      of Escherichia coli K-12 imparted a viability block on cultures grown to
      stationary phase in broth. Inclusion of the last 25 codons of the RhsA core open
      reading frame (called core-ORF) in the plasmid insert was crucial for eliciting
      this toxic effect. The toxic effect could be suppressed by including the adjacent
      Rhs component, dsORF-a1, on the multicopy plasmid. The toxic effect was enhanced
      in RpoS- strains.

PMID- 7721713
TI  - Bradyrhizobium japonicum cytochrome c550 is required for nitrate respiration but
      not for symbiotic nitrogen fixation.
AB  - Bradyrhizobium japonicum possesses three soluble c-type cytochromes, c550, c552,
      and c555. The genes for cytochromes c552 (cycB) and c555 (cycC) were
      characterized previously. Here we report the cloning, sequencing, and mutational
      analysis of the cytochrome c550 gene (cycA). A B. japonicum mutant with an
      insertion in cycA failed to synthesize a 12-kDa c-type cytochrome. This protein
      was detectable in the cycA mutant complemented with cloned cycA, which proves
      that it is the cycA gene product. The cycA mutant, a cycB-cycC double mutant, and
      a cycA-cycB-cycC triple mutant elicited N2-fixing root nodules on soybean (Nod+
      Fix+ phenotype); hence, none of these three cytochromes c is essential for
      respiration supporting symbiotic N2 fixation. However, cytochrome c550, in
      contrast to cytochromes c552 and c555, was shown to be essential for anaerobic
      growth of B. japonicum, using nitrate as the terminal electron acceptor.

PMID- 7721714
TI  - In vivo sulfhydryl modification of the ligand-binding site of Tsr, the
      Escherichia coli serine chemoreceptor.
AB  - The Escherichia coli chemoreceptor Tsr mediates an attractant response to serine.
      We substituted Cys for Thr-156, one of the residues involved in serine sensing.
      The mutant receptor Tsr-T156C retained serine- and repellent-sensing abilities.
      However, it lost serine-sensing ability when it was treated in vivo with
      sulfhydryl-modifying reagents such as N-ethylmaleimide (NEM). Serine protected
      Tsr-T156C from these reagents. We showed that [3H]NEM bound to Tsr-T156C and that
      binding decreased in the presence of serine. By pretreating cells with serine and
      cold NEM, Tsr-T156C was selectively labeled with radioactive NEM. These results
      are consistent with the location of Thr-156 in the serine-binding site. Chemical
      modification of the Tsr ligand-binding site provides a basis for simple
      purification and should assist further in vivo and in vitro investigations of
      this chemoreceptor protein.

PMID- 7721715
TI  - Characterization of cis elements that regulate the expression of glnA in
      Synechococcus sp. strain PCC 7942.
AB  - The upstream noncoding region of the Synechococcus sp. strain PCC 7942 (hereafter
      referred to as Synechococcus 7942) glnA gene was fused to the cat gene in order
      to study the expression of glnA both in Synechococcus 7942 and in Escherichia
      coli. The lack of cat expression in E. coli indicated that the glnA promoter was
      not recognized by E. coli RNA polymerase. The fused construct was integrated into
      the Synechococcus 7942 chromosome at a neutral site. Expression of the cat
      reporter gene was regulated under various nitrogen conditions in a way similar to
      that of the glnA gene. A deletion introduced at the binding site of the NtcA
      regulatory protein abolished derepression of the glnA promoter during growth in
      nitrate and under nitrogen starvation. Deletion of the sequence between the
      transcription and translation start sites of glnA prevented the repression
      observed during growth in ammonium. These results indicate that the glnA promoter
      is subject to complex regulation that involves sequences upstream and downstream
      from the transcription start site.

PMID- 7721716
TI  - Potassium/proton antiport system of growing Enterococcus hirae at high pH.
AB  - The cytoplasmic pH (pHin) of Enterococcus hirae growing at pH 9.2 was maintained
      at about 8.1. Membrane-permeating amines such as ammonia alkalinized the pHin
      from 8.1 to 9.0 at a high concentration and induced K+ extrusion. The pHin
      alkalinization was transient; the pHin fell from 9.0 to the original value of pH
      8.1, at which point K+ extrusion ceased, and remained constant. Cells accumulated
      ammonium ion to an extent stoichiometrically equivalent to the K+ loss. This
      bacterium continued to grow well under this condition. These results suggest that
      the pHin-responsive primary K+/H+ antiport system (Y. Kakinuma, and K. Igarashi,
      J. Biol. Chem. 263:14166-14170, 1988) works for the pHin regulation of this
      organism growing at a high pH.

PMID- 7721717
TI  - A two-protein component 7 alpha-cephem-methoxylase encoded by two genes of the
      cephamycin C cluster converts cephalosporin C to 7-methoxycephalosporin C.
AB  - Two genes, cmcI and cmcJ, corresponding to open reading frames 7 and 8 (ORF7 and
      ORF8) of the cephamycin C cluster of Nocardia lactamdurans encode enzymes that
      convert cephalosporin C to 7-methoxycephalosporin C. Proteins P7 and P8 (the
      products of ORF7 and ORF8 expressed in Streptomyces lividans) introduce the
      methoxyl group at C-7 of the cephem nucleus. Efficient hydroxylation at C-7 and
      transfer of the methyl group from S-adenosylmethionine require both proteins P7
      and P8, although P7 alone shows weak C-7 hydroxylase activity and strong
      cephalosporin-dependent NADH oxidase activity. Both P7 and P8 appear to be
      synthesized in a coordinated form by translational coupling of cmcI and cmcJ.
      Protein P7 contains domains that correspond to conserved sequences in cholesterol
      7 alpha-monooxygenases and to the active center of O-methyltransferases by
      comparison with the crystal structure of catechol-O-methyltransferase. Protein P8
      may act as a coupling protein for efficient hydroxylation at C-7 in a form
      similar to that of the two-component system of Pseudomonas putida p
      hydroxyphenylacetate-3-hydroxylase.

PMID- 7721718
TI  - Cloning and characterization of the gsk gene encoding guanosine kinase of
      Escherichia coli.
AB  - The Escherichia coli gsk gene encoding guanosine kinase was cloned from the
      Kohara gene library by complementation of the E. coli gsk-1 mutant allele. The
      cloned DNA fragment was sequenced and shown to encode a putative polypeptide of
      433 amino acids with a molecular mass of 48,113 Da. Minicell analysis established
      the subunit M(r) as 43,500. Primer extension analysis indicated the presence of
      an adequate Pribnow box and suggested that the transcript contained a 110-base
      leader sequence. Strains harboring the gsk gene on multicopy plasmids
      overexpressed both guanosine and inosine kinase activities. N-terminal sequence
      and amino acid composition analyses of the 43,500-M(r) polypeptide band confirmed
      the correct reading frame assignment and the identity of this band as the gsk
      gene product. Comparison of the amino acid sequence with the protein database
      revealed similarity to regions of other mononucleotide-utilizing enzymes.

PMID- 7721719
TI  - Carbon monoxide-dependent growth of Rhodospirillum rubrum.
AB  - Under dark, anaerobic conditions in the presence of sufficient nickel,
      Rhodospirillum rubrum grows with a doubling time of under 5 h by coupling the
      oxidation of CO to the reduction of H+ to H2. CO-dependent growth of R. rubrum
      UR294, bearing a kanamycin resistance cassette in cooC, depends on a medium
      nickel level ninefold higher than that required for optimal growth of coo+
      strains.

PMID- 7721720
TI  - Chemiosmotic concept of the membrane bioenergetics: what is already clear and
      what is still waiting for elucidation?
AB  - The present state of the chemiosmotic concept is reviewed. Special attention is
      paid to (i) further progress in studies on the Na(+)-coupled energetics and (ii)
      paradoxical bioenergetic effects when protonic or sodium potentials are utilized
      outside the coupling membrane (TonB-mediated uphill transports across the outer
      bacterial membrane). A hypothesis is put forward assuming that the same principle
      is employed in the bacterial flagellar motor.

PMID- 7721721
TI  - The histidine cycle: a new model for proton translocation in the respiratory heme
      copper oxidases.
AB  - A model of redox-linked proton translocation is presented for the terminal heme
      copper oxidases. The new model, which is distinct both in principle and in detail
      from previously suggested mechanisms, is introduced in a historical perspective
      and outlined first as a set of general principles, and then as a more detailed
      chemical mechanism, adapted to what is known about the chemistry of dioxygen
      reduction in this family of enzymes. The model postulates a direct mechanistic
      role in proton-pumping of the oxygenous ligand on the iron in the binuclear heme
      copper site through an electrostatic nonbonding interaction between this ligand
      and the doubly protonated imidazolium group of a conserved histidine residue
      nearby. In the model this histidine residue cycles between imidazolium and
      imidazolate states translocating two protons per event, the imidazolate state
      stabilized by bonding to the copper in the site. The model also suggests a key
      role in proton translocation for those protons that are taken up in reduction of
      O2 to water, in that their uptake to the oxygenous ligand unlatches the
      electrostatically stabilized imidazolium residue and promotes proton release.

PMID- 7721723
TI  - Composition and function of cytochrome b559 in reaction centers of photosystem II
      of green plants.
AB  - A review of a recent study of the spectral and thermodynamic properties of
      cytochrome b559 as well as of the electron transfer between b559 and photosystem
      II reaction center cofactors in isolated D1/D2/cytochrome b559 complex RC-2 is
      presented. Attention is paid to the existence of intermediary-potential (IP, +150
      mV) and extra-low-potential (XLP, -45 mV) hemes located close to the acceptor
      (quinone) and donor (P680) sides of the reaction center cofactors, respectively.
      These hemes found in isolated RC-2 probably correspond to the high-potential and
      low-potential hemes in chloroplasts, respectively. The above location of the
      hemes is believed to allow the photoreduction of the XLP heme and photooxidation
      of the IP heme. The electron transfer between the two hemes is discussed in terms
      of the cyclic electron flow and possible involvement in water splitting.

PMID- 7721722
TI  - Mechanistic and phenomenological features of proton pumps in the respiratory
      chain of mitochondria.
AB  - Various direct, indirect (kinetic and thermodynamic), and combined mechanisms
      have been proposed to explain the conversion of redox energy into a transmembrane
      protonmotive force (delta p) by enzymatic complexes of respiratory chains. The
      conceptual evolution of these models is examined. The characteristics of
      thermodynamic coupling between redox transitions of electron carriers and scalar
      proton transfer in cytochrome c oxidase and its possible involvement in proton
      pumping is discussed. Other aspects dealt with in this paper are: (i) variability
      of <--H+/e- stoichiometries, in cytochrome c oxidase and cytochrome c reductase
      and its mechanistic implications; (ii) possible models by which the reduction of
      dioxygen to water at the binuclear heme-copper center of protonmotive oxidases
      can be directly involved in proton pumping. Finally a unifying concept for proton
      pumping by the redox complexes of respiratory chain is presented.

PMID- 7721724
TI  - Mechanism of ATP synthesis by mitochondrial ATP synthase from beef heart.
AB  - Previous studies of the rate constants for the elementary steps of ATP hydrolysis
      by the soluble and membrane-bound forms of beef heart mitochondrial F1 supported
      the proposal that ATP is formed in high-affinity catalytic sites of the enzyme
      with little or no change in free energy and that the major requirement for energy
      in oxidative phosphorylation is for the release of product ATP. The affinity of
      the membrane-bound enzyme for ATP during NADH oxidation was calculated from the
      ratio of the rate constants for the forward binding step (k+1) and the reverse
      dissociation step (k-1). k-1 was accelerated several orders of magnitude by NADH
      oxidation. In the presence of NADH and ADP an additional enhancement of k-1 was
      observed. These energy-dependent dissociations of ATP were sensitive to the
      uncoupler FCCP. k+1 was affected little by NADH oxidation. The dissociation
      constant (KdATP) increased many orders of magnitude during the transition from
      nonenergized to energized states.

PMID- 7721727
TI  - Chromatin higher order structure: chasing a mirage?

PMID- 7721726
TI  - Bacterial resistance to uncouplers.
AB  - Uncoupler resistance presents a potential challenge to the conventional
      chemiosmotic coupling mechanism. In E. coli, an adaptive response to uncouplers
      was found in cell growing under conditions requiring oxidative phosphorylation.
      It is suggested that uncoupler-resistant mutants described in the earlier
      literature might represent a constitutive state of expression of this "low energy
      shock" adaptive response. In the environment, bacteria are confronted by
      nonclassical uncoupling factors such as organic solvents, heat, and extremes of
      pH. It is suggested that the low energy shock response will aid the cell in
      coping with the effects of natural uncoupling factors. The genetic analysis of
      uncoupler resistance has only recently began, and is yielding interesting and
      largely unexpected results. In Bacillus subtilis, a mutation in fatty acid
      desaturase causes an increased content of saturated fatty acids in the membrane
      and increased uncoupler resistance. The protonophoric efficiency of uncouplers
      remains unchanged in the mutants, inviting nonorthodox interpretations of the
      mechanism of resistance. In E. coli, two loci conferring resistance to CCCP and
      TSA were cloned and were found to encode multidrug resistance pumps. Resistance
      to one of the uncouplers, TTFB, remained unchanged in strains mutated for the
      MDRs, suggesting a resistance mechanism different from uncoupler extrusion.

PMID- 7721725
TI  - Chemiosmotic coupling of ion transport in the yeast vacuole: its role in
      acidification inside organelles.
AB  - Acidification inside the vacuo-lysosome systems is ubiquitous in eukaryotic
      organisms and essential for organelle functions. The acidification of these
      organelles is accomplished by proton-translocating ATPase belonging to the V-type
      H(+)-ATPase superfamily. However, in terms of chemiosmotic energy transduction,
      electrogenic proton pumping alone is not sufficient to establish and maintain
      those compartments inside acidic. Current studies have shown that the in situ
      acidification depends upon the activity of V-ATPase and vacuolar anion
      conductance; the latter is required for shunting a membrane potential (interior
      positive) generated by the positively charged proton translocation. Yeast
      vacuoles possess two distinct Cl- transport systems both participating in the
      acidification inside the vacuole, a large acidic compartment with digestive and
      storage functions. These two transport systems have distinct characteristics for
      their kinetics of Cl- uptake or sensitivity to a stilbene derivative. One shows
      linear dependence on a Cl- concentration and is inhibited by 4,4'-diisothiocyano
      2,2'-stilbenedisulfonic acid (DIDS). The other shows saturable kinetics with an
      apparent Km for Cl- of approximately 20 mM. Molecular mechanisms of the
      chemiosmotic coupling in the vacuolar ion transport and acidification inside are
      discussed in detail.

PMID- 7721728
TI  - Role of mitogen-activated protein kinase phosphatase during the cellular response
      to genotoxic stress. Inhibition of c-Jun N-terminal kinase activity and AP-1
      dependent gene activation.
AB  - Irradiation of mammalian cells with short wavelength ultraviolet light (UVC)
      evokes a cascade of phosphorylation events leading to altered gene expression.
      Both the classic mitogen-activated protein (MAP) kinases and the distantly
      related c-Jun N-terminal kinases (JNK) contribute to the response via
      phosphorylation of transcription factors including AP-1. These kinases are
      themselves regulated via reversible phosphorylation, and several recently
      identified specific MAP kinase phosphatases (MKP) have been implicated in down
      regulating MAP kinase-dependent gene expression in response to mitogens. Here, we
      provide evidence that MKP-1 plays a role in regulating transcriptional activation
      in response to UVC as well as another genotoxic agent, methyl methanesulfonate
      (MMS). We further demonstrate that JNK is a likely target for MKP-1. JNK is shown
      to be activated by UVC and MMS treatment, while MAP kinase activation occurs only
      with UVC. Like JNK activation, MKP-1 mRNA is induced by both treatments, and
      elevated MKP-1 expression coincides with a decline in JNK activity. Constitutive
      expression of MKP-1 in vivo inhibits JNK activity and reduces UVC- and MMS
      induced activation of AP-1-dependent reporter genes.

PMID- 7721729
TI  - Yeast DNA repair protein RAD23 promotes complex formation between transcription
      factor TFIIH and DNA damage recognition factor RAD14.
AB  - In Saccharomyces cerevisiae, the multisubunit RNA polymerase II general
      transcription factor TFIIH is indispensable for transcription initiation and some
      of its subunits are known to be required for nucleotide excision repair (NER) of
      DNA damaged by ultraviolet light. RAD3, a subunit of TFIIH, binds UV-damaged DNA
      in an ATP-dependent manner. It has, however, remained unclear how TFIIH is
      assembled with the other damage recognition component RAD14. Here, we demonstrate
      a higher order complex consisting of TFIIH, RAD14, and another NER protein RAD23,
      and complex formation between TFIIH and RAD14 is facilitated by the RAD23
      protein.

PMID- 7721730
TI  - Glyceraldehyde-3-phosphate ferredoxin oxidoreductase, a novel tungsten-containing
      enzyme with a potential glycolytic role in the hyperthermophilic archaeon
      Pyrococcus furiosus.
AB  - The archaeon Pyrococcus furiosus grows optimally at 100 degrees C by the
      fermentation of carbohydrates to yield acetate, CO2, and H2. Cell-free extracts
      contain very low activity of the glycolytic enzyme, glyceraldehyde-3-phosphate
      dehydrogenase, but extremely high activity of glyceraldehyde-3-phosphate
      ferredoxin oxidoreductase (GAPOR). GAPOR was purified under strictly anaerobic
      conditions. It is a monomeric, O2-sensitive protein of M(r) approximately 63,000
      which contains pterin and approximately 1 tungsten and 6 iron atoms per molecule.
      The enzyme oxidized glyceraldehyde-3-phosphate (Km 28 microM) to 3
      phosphoglycerate and reduced P. furiosus ferredoxin (Km 6 microM), but it did not
      oxidize formaldehyde, acetaldehyde, glyceraldehyde, benzaldehyde, glucose,
      glucose 6-phosphate, or glyoxylate, nor did it use NAD(P) as an electron
      acceptor. It is proposed that GAPOR has a glycolytic role and functions in place
      of glyceraldehyde-3-phosphate dehydrogenase and possibly phosphoglycerate kinase.

PMID- 7721731
TI  - Mutations which impede loop/sheet polymerization enhance the secretion of human
      alpha 1-antitrypsin deficiency variants.
AB  - alpha 1-Antitrypsin plasma deficiency variants which form hepatic inclusion
      bodies within the endoplasmic pathway include the common Z variant (Glu342-->Lys)
      and the rarer alpha 1-antitrypsin Siiyama (Ser53-->Phe). It has been proposed
      that retention of both abnormal proteins is accompanied by a common mechanism of
      loop-sheet polymerization with the insertion of the reactive center loop of one
      molecule into a beta-pleated sheet of another. We have compared the biosynthesis,
      glycosylation, and secretion of normal, Z and Siiyama variants of alpha 1
      antitrypsin using Xenopus oocytes. Siiyama and Z alpha 1-antitrypsin both
      duplicated the secretory defect seen in hepatocytes that results in decreased
      plasma alpha 1-antitrypsin levels. Digestion with endoglycosidase H localized
      both variants to a pre-Golgi compartment. The mutation Phe51-->Leu abolished
      completely the intracellular blockage of Siiyama alpha 1-antitrypsin and reduced
      significantly the retention of Z alpha 1-antitrypsin. The secretory properties of
      M and Z alpha 1-antitrypsin variants containing amino acid substitutions designed
      to decrease loop mobility and sheet insertion were investigated. A reduction in
      intracellular levels of Z alpha 1-antitrypsin was achieved with the replacement
      of P11/12 alanines by valines. Thus a decrease in Z and Siiyama alpha 1
      antitrypsin retention was observed with mutations which either closed the A sheet
      or decreased loop mobility at the loop hinge region.

PMID- 7721732
TI  - Natural DNA precursor pool asymmetry and base sequence context as determinants of
      replication fidelity.
AB  - Previous studies showed a complex relationship between nucleotide composition of
      a gene and the rate of the gene's evolutionary variation. We have investigated
      mechanisms by constructing M13 phagemids containing part of the Escherichia coli
      lacZ gene, in which an opal codon is flanked either by nine adenine-thymine base
      pairs on each side, or by nine guanine-cytosine pairs, or by its wild-type
      sequence context. Reversions or pseudoreversions within the opal codon yield a
      lacZ alpha-peptide that can undergo alpha-complementation and yield a blue plaque
      when plated with a chromogenic substrate. When these constructs were replicated
      in HeLa cell extracts, in the presence of equimolar deoxyribonucleoside
      triphosphate (dNTP) mixtures, reversion was near background levels in both the AT
      rich and GC-rich contexts. By contrast, when the DNAs were replicated at dNTP
      concentrations approximating those in HeLa cell nuclei, increases over background
      were seen in all three contexts. Replication of the phagemids in vivo led to even
      higher mutation frequencies. Replication in the presence of dGMP, added to
      inhibit proofreading, caused extraordinarily high reversion frequencies in the GC
      flanked opal codon. Apparently, dNTP concentrations approximating intracellular
      concentrations are mildly but significantly mutagenic, and pool asymmetries and
      base sequence context both contribute to the natural fidelity of DNA replication.

PMID- 7721733
TI  - Microsecond generation of oxygen-bound cytochrome c oxidase by rapid solution
      mixing.
AB  - Current understanding of the oxygen reduction and proton translocation processes
      in cytochrome c oxidase is largely derived from the data obtained by a
      nonphysiological method for initiating the catalytic reaction: photolyzing carbon
      monoxide (CO) from the CO-inhibited enzyme in the presence of oxygen (O2).
      However, considerable evidence suggests that the use of CO introduces artifacts
      into the reaction mechanism. We have therefore developed a rapid solution mixer
      with a mixing time of 20 microseconds to study the catalytic reaction by directly
      mixing the enzyme with O2 without using CO. Unexpectedly, the resonance Raman
      scattering detected for the first 120 microseconds after the mixing show that the
      CO influences neither the structure of the primary oxy-intermediate, its rate of
      decay, nor the rate of oxidation of cytochrome a. This implies that CO has an
      effect on the later stages of the catalytic process, which may involve the proton
      translocation steps, and calls for the re-examination of the catalytic process by
      using the direct mixing method. In addition, these results demonstrate the
      feasibility of using the rapid mixing device for the study of biological
      reactions in the microsecond time domain.

PMID- 7721734
TI  - Inactivation of the intrinsic activity of pro-urokinase by diisopropyl
      fluorophosphate is reversible.
AB  - Single chain urokinase-type plasminogen activator or pro-urokinase (pro-UK) has
      been reported to have a significant intrinsic amidolytic and plasminogen
      activator activity, estimated to be about 0.2-0.6% that of two-chain urokinase
      (UK). However, it has also been suggested that this reported activity is related
      entirely to trace UK contaminants generated during the analytic procedures. In an
      attempt to resolve this controversy, it was decided to measure the incorporation
      of diisopropyl fluorophosphate (DFP) by pro-UK and UK. Surprisingly, it was found
      that although > 98% of the apparent intrinsic activity of pro-UK was inhibited by
      5 mM DFP, > 97% of this activity was recoverable after exhaustive dialysis of the
      preparation. This finding could not be explained by UK generation, which was
      excluded. Instead, the findings indicated that DFP inhibition of pro-UK, in
      contrast to UK and other serine proteases, was largely reversible. The reaction
      rate of the reversible inhibition was significantly slower than that of
      irreversible inhibition by DFP. When the hydrolysis of DFP (2 mM) during
      incubation (37 degrees C) with or without pro-UK (20 microM) was compared, a > 5
      fold acceleration of DFP hydrolysis in the presence of pro-UK was found, whereas
      little loss of DFP occurred in the presence of UK (20 microM), consistent with
      1:1 stoichiometry. This suggested that pro-UK acted as a slow DFPase in the
      reaction, a finding consistent with a reversible DFP-enzyme reaction. It was
      concluded that pro-UK has a distinct and measurable intrinsic catalytic activity,
      which is qualitatively unique and thereby distinguishable from that of UK as well
      as other serine proteases.

PMID- 7721735
TI  - Mutations at Pro67 in the RecA protein P-loop motif differentially modify
      coprotease function and separate coprotease from recombination activities.
AB  - The functional significance of residues in the RecA protein P-loop motif was
      assessed by analyzing 100 unique mutants with single amino acid substitutions in
      this region. Comparison of the effects on the LexA coprotease and recombination
      activities shows that Pro67 is unique among these residues because only at this
      position did we find substitutions that caused differential effects on these
      functions. One mutant, Pro67-->Trp, displays high constitutive coprotease
      activity and a moderate inhibitory effect on recombination functions. Glu and Asp
      substitutions result in low level constitutive coprotease activity but
      dramatically reduce recombination activity. The purified Pro67-->Trp protein
      shows a completely relaxed specificity for NTP cofactors in LexA cleavage assays
      and can use shorter length oligonucleotides as cofactors for cleavage of lambda
      cI repressor than can wild type RecA. Interestingly, both the mutant protein and
      wild type RecA can use very short oligonucleotides, e.g. (dA)6 and (dT)6, as
      cofactors for LexA cleavage. We have also found two mutations at position 67,
      which are completely defective for LexA coprotease activity in vivo but still
      maintain recombinational DNA repair (Pro67-->Lys) and homologous recombination
      (Pro67-->Lys and Pro67-->Arg) activities. These findings show that the
      recombination activities of RecA are mutationally separable from the coprotease
      function and that Pro67 is located in a functionally important position in the
      RecA structure.

PMID- 7721736
TI  - A difference Fourier transform infrared spectroscopic study of chlorophyll
      oxidation in hydroxylamine-treated photosystem II.
AB  - In oxygenic photosynthesis, photosystem II is the chlorophyll-containing reaction
      center that carries out the light-induced transfer of electrons from water to
      plastoquinone. Fourier transform infrared spectroscopy can be used to obtain
      information about the structural changes that accompany electron transfer in
      photosystem II. The vibrational difference spectrum associated with the reduction
      of photosystem II acceptor quinones is of interest. Previously, a high
      concentration of the photosystem II donor, hydroxylamine, has been used to obtain
      a spectrum attributed to QA- -QA (Berthomieu, C., Nabedryk, E., Mantele, W. and
      Breton, J. FEBS Lett. (1990) 269, 363). Here, we use electron paramagnetic
      resonance, Fourier transform infrared spectroscopy, and 15N isotopic labeling to
      show that the difference infrared spectrum, obtained under these conditions, also
      exhibits a contribution from the oxidation of chlorophyll.

PMID- 7721737
TI  - Novel gastrin receptors mediate mitogenic effects of gastrin and processing
      intermediates of gastrin on Swiss 3T3 fibroblasts. Absence of detectable
      cholecystokinin (CCK)-A and CCK-B receptors.
AB  - We have reported previously mitogenic effects of gastrin on several immortalized
      and neoplastic cell lines, including Swiss 3T3 fibroblasts. Receptor subtypes,
      cholecystokinin (CCK)-A and CCK-B, for a closely related peptide,
      cholecystokinin, were recently cloned. These studies were undertaken to
      investigate if CCK-A- and CCK-B receptors were perhaps mediating the mitogenic
      effects of gastrin on Swiss 3T3 cells. Receptor antagonists that inhibit the
      biological effects and binding of peptides to the CCK-A (L-364,718 (L18)) and CCK
      B (L-365,260 (L60)) receptors were ineffective toward inhibiting the binding and
      proliferative effects of gastrin on Swiss 3T3 cells. Radiolabeled L18 and L60
      demonstrated no binding to the cells, indicating that CCK-A and CCK-B receptors
      may be absent on Swiss 3T3 cells. Radiolabeled CCK-8, gastrin, L18, and L60, on
      the other hand, demonstrated specific binding to a pancreatic cancer cell line
      (AR42J cells) (used as a positive control). In cross-linking studies the
      molecular mass of the major band of gastrin receptors (GR) on Swiss 3T3 cells was
      determined to be approximately 45 kDa. The mitogenic potency of 0.1-1.0 nM
      gastrin-like peptides on Swiss 3T3 cells was in the order of G1-17 > or = G1-17
      Gly > G5-17 > or = G5-17-Gly > G2-17 > CCK-8-Gly > or = G1-17-Lys > or = CCK-8.
      The relative binding affinity of the peptides (based on the dose-dependent
      inhibition of binding of 125I-G1-17 to Swiss 3T3 cells) was similar to the
      relative mitogenic potency of the peptides as given above. Furthermore, G1-17-Gly
      was equally effective as G1-17 in displacing the binding of 125I-G1-17 to the 45
      kDa GR from the Swiss 3T3 cells. Based on these studies it became evident that
      the novel gastrin preferring GR, expressed by Swiss 3T3 cells, binds and mediates
      the mitogenic effects of not only the mature (amidated) forms of gastrin-like
      peptides but also binds and mediates the mitogenic effects of glycine-extended
      forms of gastrin-like peptides. Possible mRNA expression of CCK-A and CCK-B
      receptor subtypes by gastrin-responsive rodent intestinal and fibroblast cell
      lines (Swiss 3T3, IEC-6, CA) was measured by the methods of Northern blot
      analysis and reverse transcriptase-polymerase chain reaction. mRNA from rat
      pancreas, AR42J cells, and rat antrum served as positive controls.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7721738
TI  - Optical melting of 128 octamer DNA duplexes. Effects of base pair location and
      nearest neighbors on thermal stability.
AB  - The use of short oligonucleotide probes is finding increased application in DNA
      sequencing and genome characterization techniques, but a lack of knowledge of the
      hybridization properties of short duplexes hinders their use. Melting data were
      acquired on 128 DNA duplexes based on the length proposed in sequencing by
      hybridization procedures and formed from the general sequences 5'-XYZTGGAC-3',5'
      GTCCAXYZ-3',5'-GCXYZGAC-3', and 5'-GTCXYZGC-3' where X, Y, and Z are either A, T,
      G, or C. These molecules were designed to elucidate the effects of location and
      nearest-neighbor stacking on the stability of base pairing in short DNA duplexes.
      The type of base pairs present had a major effect on stability, but was
      insufficient to predict stability without the inclusion of nearest-neighbor
      terms. Furthermore, the addition of information on position, or distance from the
      end, of the nearest-neighbor doublets led to statistically better fitting of the
      melting data. However, the positionally dependent stabilization differences are
      small compared with the contributions of base pairing and stacking.

PMID- 7721739
TI  - M1 muscarinic receptors heterologously expressed in cardiac myocytes mediate Ras
      dependent changes in gene expression.
AB  - Stimulation of alpha 1-adrenergic receptors in neonatal ventricular
      cardiomyocytes induces hypertrophic changes including activation of the atrial
      natriuretic factor (ANF) gene. This receptor couples to Gq to activate
      phospholipase C (PLC) and protein kinase C, which have been implicated as
      mediators of the hypertrophic response. To directly determine whether receptor
      coupling to Gq/PLC is sufficient to induce ANF expression, we expressed wild-type
      and chimeric muscarinic cholinergic receptors (mAChRs) with altered G-protein
      coupling properties in cardiac myocytes and examined their ability to activate an
      ANF promoter/luciferase reporter gene. The cholinergic agonist carbachol failed
      to induce transcriptional activation of the ANF reporter gene through endogenous
      Gi-linked M2mAChRs or in cells transfected with M2mAChRs. In contrast, in cells
      transfected with M1mAChRs, which effectively couple to Gq/PLC, carbachol
      increased ANF reporter gene expression 10-fold and also increased ANF protein, as
      determined by immunofluorescence. Carbachol-mediated ANF gene expression was
      inhibited by the mAChR antagonist pirenzepine with a Ki value characteristic of
      an M1mAChR. Studies using chimeric M1- and M2mAChRs demonstrated that the N
      terminal 21 amino acids of the third intracellular loop of the M1mAChR were
      required for receptor coupling to ANF gene expression. This region, previously
      shown to specify receptor coupling to Gq/PLC, also conferred partial activity to
      a chimeric M2 receptor. We further demonstrated that M1mAChR coupling to ANF gene
      expression was Ras-dependent since co-expression of dominant-interfering Ala-15
      Ras inhibited M1mAChR-induced ANF expression by 60%. In contrast, ANF expression
      induced by the chimeric M2 receptor was not blocked by dominant-interfering Ras.
      We suggest that receptor coupling to Gq/PLC is sufficient to induce ANF
      expression and that a Ras-dependent pathway contributes additional signals
      required for maximal M1mAChR-mediated ANF gene expression.

PMID- 7721740
TI  - Species-specific agonist/antagonist activities of human interleukin-4 variants
      suggest distinct ligand binding properties of human and murine common receptor
      gamma chain.
AB  - Interleukin-4 (IL-4) is a pleiotropic cytokine eliciting various responses in
      target cells upon binding to its receptor. Activation of the IL-4 receptor
      probably involves interaction of the ligand with both the IL-4 receptor alpha
      subunit (IL-4R alpha) and the common gamma chain (c gamma). Although human and
      murine IL-4 receptor alpha chains are specific for IL-4 from the same species,
      murine c gamma can form a signal-competent complex with human IL-4R alpha (hIL-4R
      alpha) and human IL-4 (hIL-4). We have generated a hIL-4 responsive murine
      myeloid cell line (FDC-4G) expressing a chimera comprising the extracellular
      domain of human IL-4R alpha and the intracellular domain of human granulocyte
      colony-stimulating factor receptor (hG-CSFR). This hybrid receptor was shown to
      form a complex with hIL-4 and the murine c gamma-chain. Biological activities of
      human IL-4 variants on murine FDC-4G cells and on the human erythroleukemic cell
      line TF-1 displayed a strikingly different pattern. Single amino acid
      replacements at two different positions in the C-terminal helix of hIL-4, the
      region of the previously defined "signaling site," lead to an inverse
      agonist/antagonist behavior of the resulting cytokines in the two cellular
      systems. From these findings we conclude that upon formation of the activated IL
      4 receptor complex murine and human c gamma interact with hIL-4 in a
      geometrically different fashion.

PMID- 7721741
TI  - Truncation of the carboxyl-terminal region of the rat parathyroid hormone
      (PTH)/PTH-related peptide receptor enhances PTH stimulation of adenylyl cyclase
      but not phospholipase C.
AB  - The functional role of the rat parathyroid hormone(PTH)/PTH-related peptide
      (PTHrP) receptor's carboxyl-terminal region was characterized by comparing the
      binding and signaling properties of receptors that have 78 and 111 amino acid
      deletions (R513 and R480, respectively), with those of the 591-amino acid wild
      type (WT) receptor. R480 and R513 have 4- and 1.5-fold lower apparent Kd values
      for rat PTH-(1-34) (rPTH), compared with the WT receptor (WT, 1.81 +/- 0.19 nM;
      R513, 1.24 +/- 0.12 nM; R480, 0.48 +/- 0.05 nM, mean +/- S.E.). PTH (100 nM)
      stimulated cAMP accumulation and polyphosphoinositide hydrolysis both correlated
      positively with receptor expression. However, whereas PTH-stimulated
      polyphosphoinositide hydrolysis was indistinguishable among WT and either
      truncated mutant at comparable levels of expressed receptors, maximal PTH
      stimulated cAMP accumulation was 4-6- and 2-3-fold higher in cells expressing
      R480 and R513, respectively. Furthermore, pretreatment of COS-7 cells with 100
      ng/ml of pertussis toxin (PTX) enhanced PTH-stimulated cAMP accumulation in cells
      expressing the WT receptor, but failed to do so in cells expressing either R480
      or R513. Thus, sequences in the PTH/PTHrP receptor's carboxyl-terminal tail lower
      the affinity of the WT receptor for agonist; directly interact with, or
      indirectly facilitate the interaction of the receptor with a PTX-sensitive G
      protein that inhibits adenylyl cyclase; and decrease the efficacy with which the
      receptor interacts with Gs.

PMID- 7721742
TI  - Regulation of phospholipase D in HL60 cells. Evidence for a cytosolic
      phospholipase D.
AB  - Phospholipase D (PLD) activity that was stimulated by guanosine 5'-O-(3
      thiotriphosphate) (GTP gamma S) was detected in cytosol and membranes of HL60
      cells. GTP gamma S-stimulated PLD activity was detected in the membranes when
      exogenous labeled phosphatidylcholine was used in the presence of
      phosphatidylethanolamine and phosphatidylinositol 4,5-bisphosphate, but not when
      [3H]myristic acid-labeled endogenous substrate was used. Cytosolic PLD co
      chromatographed with small GTP-binding proteins on anion-exchange columns, but
      subsequent chromatography separated these. Reconstitution studies demonstrated
      ADP ribosylation factor (ARF) as a regulator of cytosolic PLD, whereas the Rho
      proteins RhoA and CDC42Hs were ineffective. The cytosolic enzyme showed very
      little activity in the absence of GTP gamma S and was stimulated by 2 mM Ca2+,
      whereas the membrane enzyme had significant basal activity and was inhibited by
      Ca2+. Rho-specific GDP dissociation inhibitor inhibited GTP gamma S stimulation
      of membrane PLD activity in the presence and absence of cytosol. The stimulation
      in GDP dissociation inhibitor-treated membranes could be partially recovered by
      the addition of recombinant Rho proteins (RhoA, Rac1, CDC42Hs). RhoA and Rac1
      were also stimulatory in untreated membranes. However, Western blot analysis of
      membranes showed the presence of RhoA, but not Rac1 or CDC42Hs, suggesting that
      RhoA was the endogenous small GTP-binding protein involved in GTP-dependent PLD
      activity in membranes in the absence of cytosol. ARF also stimulated the membrane
      PLD in the presence of GTP gamma S, and the combination of RhoA and ARF showed a
      synergistic effect. These results show the presence of ARF-dependent PLD activity
      in both cytosol and membranes. The membranes contain another PLD activity for
      which the endogenous regulator appears to be RhoA. The data suggest the existence
      of at least two different PLD isozymes in HL60 cells.

PMID- 7721743
TI  - A post-translational modification of the photosystem II subunit CP29 protects
      maize from cold stress.
AB  - The resistance of maize plants to cold stress has been associated with the
      appearance of a new chlorophyll a/b binding protein in the thylakoid membrane
      following chilling treatment in the light. The cold-induced protein has been
      isolated, characterized by amino acid sequencing, and pulse labeled with
      radioactive precursors, showing that it is the product of post-translational
      modification by phosphorylation of the minor chlorophyll a/b protein CP29 rather
      than the product of a cold-regulated gene or an unprocessed CP29 precursor. We
      show here that the CP29 kinase activity displays unique characteristics differing
      from previously described thylakoid kinases and is regulated by the redox state
      of a quinonic site. Finally, we show that maize plants unable to perform
      phosphorylation have enhanced sensitivity to cold-induced photoinhibition.

PMID- 7721744
TI  - Sodium-independent currents of opposite polarity evoked by neutral and cationic
      amino acids in neutral and basic amino acid transporter cRNA-injected oocytes.
AB  - To elucidate the electrical events associated with the movement of amino acids by
      the neutral and basic amino acid transporter (NBAT)-encoded protein (Yan, N.,
      Mosckovitz, R., Gerber, L.D., Mathew, S., Murty, V.V. V.S., Tate, S.S., and
      Udenfriend, S. (1994) Proc. Natl. Acad. Sci. USA 91, 7548-7552), we have
      investigated the membrane potential and current changes associated with the
      increased transport of amino acids across the cell membrane of NBAT cRNA-injected
      Xenopus laevis oocytes. Superfusion of 0.05 mM L-phenylalanine, in current
      clamped NBAT-injected oocytes, caused a hyperpolarization (8.5 +/- 0.9 mV), but
      superfusion of L-arginine caused a depolarization (18.3 +/- 1.3 mV). In voltage
      clamped (-60 mV) oocytes, superfusion of L-phenylalanine evoked a sodium- and
      chloride-independent, saturable (Km = 0.34 +/- 0.02 mM, Imax = 31.3 +/- 0.5 nA),
      outward current. This outward current was reduced in the presence of high
      external [K] and was barium-sensitive. Outward currents were also evoked by L
      leucine, L-glutamine, L-alanine, D-phenylalanine, and L-beta-phenylalanine.
      Superfusion of L-arginine evoked a saturable (Km = 0.09 +/- 0.02 mM, Imax = -29.2
      +/- 1.3 nA) inward current; L-lysine and D-arginine also evoked inward currents.
      L-Glutamate and beta-alanine failed to evoke any currents. Effluxes of L
      [3H]phenylalanine and L-[3H]arginine were trans-stimulated in the presence of
      either amino acid. Flux-current comparisons indicated amino acid:charge movement
      stoichiometry of 1:1 for both neutral and cationic amino acids. These findings
      indicate that the amino acid transport activity(ies) expressed in NBAT cRNA
      injected oocytes is electrogenic by a mechanism including the outward movement of
      a net positive charge (potassium ion or cationic amino acid) in exchange for
      uptake of a neutral amino acid.

PMID- 7721745
TI  - The major protein of guayule rubber particles is a cytochrome P450.
      Characterization based on cDNA cloning and spectroscopic analysis of the
      solubilized enzyme and its reaction products.
AB  - Guayule plants accumulate large quantities of rubber within parenchyma cells of
      their stembark tissues. This rubber is packed within discrete organelles called
      rubber particles composed primarily of a lipophilic, cis-polyisoprene core, small
      amounts of lipids, and several proteins, the most abundant of which is the M(r)
      53,000 rubber particle protein (RPP). We have cloned and sequenced a full-length
      cDNA for RPP and show that it has 65% amino acid identity and 85% similarity to a
      cytochrome P450 known as allene oxide synthase (AOS), recently identified from
      flaxseed. RPP contains the same unusual heme-binding region and possesses a
      similar defective I-helix region as AOS, suggesting an equivalent biochemical
      function. Spectral analysis of solubilized RPP verifies it as a P450, and
      enzymatic assays reveal that it also metabolizes 13(S)-hydroperoxy-(9Z,11E)
      octadecadienoic acid into the expected ketol fatty acids at rates comparable with
      flaxseed AOS. RPP is unusual in that it lacks the amino-terminal membrane anchor
      and the established organelle targeting sequences found on other conventional
      P450s. Together, these factors place RPP in the CYP74 family of P450s and
      establish it as the first P450 localized in rubber particles and the first
      eukaryotic P450 to be identified outside endoplasmic reticulum, mitochondria, or
      plastids.

PMID- 7721746
TI  - Molecular cloning and characterization of the G protein gamma subunit of cone
      photoreceptors.
AB  - The phototransduction process in cones has been proposed to involve a G protein
      that couples the signal from light-activated visual pigment to the effector
      cyclic GMP phosphodiesterase. Previously, we have identified and purified a G
      beta gamma complex composed of a G beta 3 isoform and an immunochemically
      distinct G gamma subunit (G gamma 8) from bovine retinal cones (Fung, B. K.-K.,
      Lieberman, B. S., and Lee, R. H. (1992) J. Biol. Chem. 267, 24782-24788; Lee, R.
      H., Lieberman, B.S., Yamane, H. K., Bok, D., and Fung, B. K.-K. (1992a) J. Biol.
      Chem. 267, 24776-24781). Based on the partial amino acid sequence of this cone G
      gamma 8, we screened a bovine retinal cDNA library and isolated a cDNA clone
      encoding G gamma 8. The cDNA insert of this clone includes an open reading frame
      of 207 bases encoding a 69-amino acid protein. The predicted protein sequence of
      G gamma 8 shares a high degree of sequence identity (68%) with the G gamma (G
      gamma 1) subunit of rod transducin. Similar to rod G gamma 1, it terminates in a
      CIIS motif that is the site for post-translational modification by farnesylation.
      Messenger RNA for G gamma 8 is present at a high level in the retina and at a
      very low level in the lung, but is undetectable in other tissues. Immunostaining
      of bovine retinal sections with an antipeptide antibody against the N-terminal
      region of G gamma 8 further shows a differential localization of G gamma 8 to
      cones with a pattern indistinguishable from that of G beta 3. This finding
      suggests that G beta 3 gamma 8 is a component of cone transducin involved in cone
      phototransduction and color vision.

PMID- 7721747
TI  - Functional roles of in vivo footprinted DNA motifs within an alpha-globin
      enhancer. Erythroid lineage and developmental stage specificities.
AB  - Transcriptional regulation of the human alpha-like globin genes, embryonic zeta 2
      and adult alpha, during erythroid development is mediated by a distal enhancer,
      HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of
      multiple nuclear factor binding motifs that are occupied in vivo in an erythroid
      lineage- and developmental stage-specific manner. We have systematically analyzed
      the functional roles of these factor binding motifs of HS-40 by site-directed
      mutagenesis and transient expression assay in erythroid cell cultures. Three of
      these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively
      regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562
      cells and the adult alpha-globin promoter activity in adult erythroid MEL cells.
      On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and
      negative regulatory effects on the zeta 2-globin promoter activity in K562 cells,
      and this dual function appears to be modulated through differential binding of
      the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in
      the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic
      footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced
      MEL cells but not in K562 cells. These studies have defined the regulatory roles
      of the different HS-40 motifs. The remarkable correlation between genomic
      footprinting data and the mutagenesis results also suggests that the erythroid
      lineage- and developmental stage-specific regulation of human alpha-like globin
      promoters is indeed modulated by stable binding of specific nuclear factors in
      vivo.

PMID- 7721748
TI  - The protooncogene c-jun contains an unusual estrogen-inducible enhancer within
      the coding sequence.
AB  - Estrogens have previously been shown to induce c-jun mRNA levels in target cells
      during hormone induced proliferation, and this appears to be a primary hormonal
      response involving transcriptional activation. In this report we have now
      identified an estrogen dependent enhancer within the coding sequence of c-jun.
      This element has the sequence GCAGAnnnTGACC which is identical to the consensus
      estrogen response element GGTCAnnnTGACC in the second half site, but varies
      considerably in the first half site. Synthetic oligodeoxynucleotides containing
      this jun sequence bind the estrogen receptor in cell-free studies using a
      competitive band shift assay with the consensus element. The jun element also
      confers hormone inducibility to reporter plasmids in yeast and mammalian based
      transcriptional systems. Structure-function studies illustrate that the TGACC
      half-site and its immediate flanking dinucleotides, but not the GCAGA half-site,
      are required for estrogen receptor binding. In contrast, both the GCAGA and TGACC
      half-sites are obligatory for hormone-inducible transcriptional activation. These
      results suggest a model in which the estrogen receptor functions as a heterodimer
      to regulate transcription of the c-jun protooncogene. Coupled with reports of
      estrogen response elements in c-fos and estrogenic induction of c-fos and c-jun
      in vivo, these findings also support a role for AP-1 components as early response
      genes in estrogen-induced proliferation.

PMID- 7721749
TI  - Transcriptional analysis of acetylcholine receptor alpha 3 gene promoter motifs
      that bind Sp1 and AP2.
AB  - In this study, we performed an analysis of the neuronal nicotinic acetylcholine
      receptor alpha 3 subunit gene promoter region, -238/+47, to identify cis and
      trans elements that are important for basal activity in PC12 cells. Sequence
      analyses of the alpha 3 promoter and footprint assays revealed an Sp1 binding
      site between -79 and -57 (termed the alpha 3 GA motif) and an AP2 binding site
      between -30 and -7. Using mobility shift analysis, we found that PC12 cell
      extracts contain proteins that specifically bind to the alpha 3 GA motif and are
      immunologically related to Sp1. Mutation of the alpha 3 GA motif, which prevented
      binding of Sp1, resulted in a 75% decrease in promoter activity. Mutation of the
      AP2 site resulted in only a minor loss of promoter activity, which is consistent
      with the lack of AP2 binding activity in PC12 extracts. In Drosophila Schneider
      line 2 (S2) cell cotransfection assays, Sp1 activated the alpha 3 promoter in a
      GA motif-dependent manner. Furthermore, multimerization of the GA motif upstream
      of the beta-globin TATA box conferred Sp1 responsiveness. Our results indicate
      that Sp1 can activate transcription through direct interaction with the alpha 3
      GA motif and that this motif plays a major role in alpha 3 promoter basal
      activity in PC12 cells.

PMID- 7721750
TI  - The role of cysteine residues in the erythrocyte plasma membrane anion exchange
      protein, AE1.
AB  - AE1 (Band 3), a congruent to 110-kDa integral plasma membrane protein,
      facilitates the electroneutral movement of Cl- and HCO3- across the erythrocyte
      membrane and serves as the primary attachment site for the erythrocyte spectrin
      actin cytoskeleton. In this investigation, we have characterized the role of
      native cysteines in the function of AE1. We have constructed a mutant version of
      human AE1 (AE1C-) in which all five cysteines of AE1 were replaced with serines.
      Wild-type and AE1C- cDNAs were expressed by transient transfection of human
      embryonic kidney cells. Two of the mutated cysteines in AE1C- are in a region
      involved in ankyrin binding, and ankyrin binding has previously been shown to be
      sensitive to the oxidation state of these cysteines. However, the KD values for
      ankyrin binding by AE1 and AE1C- were indistinguishable, suggesting that AE1
      cysteines are not essential components of the ankyrin-binding site. Using size
      exclusion chromatography, both AE1 and AE1C- were found to associate as a mixture
      of dimers and high molecular mass complexes. The rate of anion exchange by AE1C-,
      as measured in a reconstituted microsome sulfate transport assay, was
      indistinguishable from that by AE1 and was inhibited by 4,4'
      diisothiocyanodihydrostilbene-2,2'-disulfonate. We conclude that the cysteines of
      AE1 are not required for the anion exchange or cytoskeletal binding roles of the
      protein.

PMID- 7721751
TI  - Region-specific activity of the plasma membrane Ca2+ pump and delayed activation
      of Ca2+ entry characterize the polarized, agonist-evoked Ca2+ signals in exocrine
      cells.
AB  - The initial release of Ca2+ from the intracellular Ca2+ stores is followed by a
      second phase during which the agonist-dependent Ca2+ response becomes sensitive
      to the extracellular Ca2+, indicating the involvement of the plasma membrane (PM)
      Ca2+ transport systems. The time course of activation of these transport systems,
      which consist of both Ca2+ extrusion and Ca2+ entry pathways, is not well
      established. To investigate the participation of these processes during the
      agonist-evoked Ca2+ response, isolated pancreatic acinar cells were exposed to
      maximal concentrations of an inositol 1,4,5-trisphosphate-mobilizing agonist
      (acetylcholine, 10 microM) in different experimental conditions. Following the
      increase of [Ca2+]i, there was an almost immediate activation of the PM Ca2+
      extrusion system, and maximal activity was reached within less than 2s. The rate
      of Ca2+ extrusion was dependent on the level of [Ca2+]i, with a steep activation
      at values just above the resting [Ca2+]i and reached a plateau value at 700 nM
      Ca2+. In contrast, the PM Ca2+ entry pathway was activated with a much slower
      time course. There was also a delay of 3-4 s between the maximal effective
      depletion of the intracellular Ca2+ stores and the activation of this entry
      pathway. By use of digital imaging data, the PM Ca2+ transport systems were also
      analyzed independently in two regions of the cells, the lumenal and the basal
      poles. With respect to the activation of the Ca2+ entry pathways, no significant
      difference existed between these two regions. In contrast, the PM Ca2+ pump
      displayed a different pattern of activity in these regions. In the basal pole,
      the pump activity was more sensitive to changes of [Ca2+]i and had a higher
      maximal activity. Also, in the lumenal pole, the pump became saturated at values
      of [Ca2+]i around 700 nM, whereas at the basal pole [Ca2+]i had a biphasic effect
      on the pump activity, and higher [Ca2+]i inhibited the pump. It is argued that
      these differences in sensitivity to the levels of [Ca2+]i and the different
      relationship between [Ca2+]i and the rate of extrusion at the two functional
      poles of the pancreatic acinar cells indicate that the plasma membrane Ca2+
      ATPase might play an important role in the polarization of the Ca2+ response.

PMID- 7721752
TI  - Structure of a novel oligosaccharide-mycosporine-amino acid ultraviolet A/B
      sunscreen pigment from the terrestrial cyanobacterium Nostoc commune.
AB  - Water-soluble UV-A/B-absorbing pigments are secreted by cells of the cosmopolitan
      terrestrial cyanobacterium Nostoc commune. The pigments constitute a complex
      mixture of monomers with molecular masses of up to 1801 Da. Two different
      chromophores with absorption maxima at 312 and 335 nm are linked to different
      amino acids and to oligosaccharides consisting of galactose, glucose, xylose,
      glucuronic acid, and glucosamine. The 335 nm chromophore is a 1,3
      diaminocyclohexen derivative, while the chromophore with an absorption maximum at
      312 nm is most likely a 3-aminocyclohexen-1-one derivative. These UV-inducible
      substances are the first mycosporines to be described covalently linked to
      oligosaccharides. The pigments are located in the extracellular glycan sheath of
      Nostoc colonies, where they form complexes of extremely high molecular mass that
      are attached noncovalently to the glycan sheath. Pigments occur in concentrations
      that permit the cells to attenuate a significant part of incident UV-B radiation.

PMID- 7721753
TI  - Requirement of b-myb function for survival and differentiative potential of human
      neuroblastoma cells.
AB  - The B-myb gene belongs to a family of transcription factors that also includes A
      myb and c-myb. B-myb is expressed in many cell types including human
      neuroblastoma cells. Here we demonstrate that B-myb expression is down-regulated
      during retinoic acid-induced neural and glial differentiation of neuroblastoma
      cells. This modulation is an early event, is maintained at late times of
      induction, and is in part regulated at the transcriptional level. Constitutive
      expression of B-myb prevents retinoic acid-induced neural differentiation as
      reflected by morphological features and the expression of (or lack of)
      biochemical markers associated with the undifferentiated phenotype. Furthermore,
      the expression of antisense B-myb transcripts does not allow the rescue of viable
      cells, suggesting an important role for B-myb in the survival of neuroblastoma
      cells. These results indicate that B-myb plays a functional role in the
      differentiative potential of neuroblastoma cells, raising the possibility that
      this gene is one of the nuclear regulators in the cascade of events leading to
      cellular differentiation.

PMID- 7721754
TI  - Cleavage of factor VIII light chain is required for maximal generation of factor
      VIIIa activity.
AB  - Thrombin-catalyzed activation of heterodimeric factor VIII occurs by limited
      proteolysis, yielding subunits A1 and A2 derived from the heavy chain (HC) and A3
      C1-C2 derived from the light chain (LC). The roles of these cleavages in the
      function of procoagulant activity are poorly understood. To determine whether LC
      cleavage contributes to the potentiation of factor VIII activity, factor VIII
      heterodimers were reconstituted from native HC and either thrombin-cleaved LC (A3
      C1-C2) or intact LC and purified by Mono S chromatography. The reconstituted
      factor VIII form containing the A3-C1-C2 subunit had a specific activity (2
      units/micrograms) that was approximately 3-fold greater than that of the
      reconstituted factor VIII form containing native LC (0.6 units/microgram). Factor
      Xa generation assays using the hybrid heterodimer showed an initial rate that was
      unaffected by the presence of von Willebrand factor and a reduced lag time when
      compared with the native heterodimer. The A1/A3-C1-C2 dimer was dissociated by
      chelation, and the purified A1 subunit was reacted with either the A3-C1-C2
      subunit or the LC in the presence of Mn2+ to reconstitute the dimer. Factor VIIIa
      heterotrimers were reconstituted from either A1/A3-C1-C2 or A1/LC plus the A2
      subunit. The authentic factor VIIIa heterotrimer (A1/A3-C1-C2/A2) had 3-fold
      greater activity than the form containing the LC. However, upon reaction with
      thrombin, the activity of the latter form was increased to that of the factor
      VIIIa form containing native subunits. The incremental increase in fluorescence
      anisotropy of fluorescein-Phe-Phe-Arg chloromethyl ketone-modified factor IXa was
      markedly greater in the presence of HC/A3-C1-C2 (delta r = 0.037) compared with
      HC/LC (delta r = 0.011) and approached the value obtained with factor VIIIa
      (delta r = 0.051). These results suggest that cleavage of factor VIII LC directly
      contributes to the potentiation of coagulant activity by modulating the
      conformation of the factor IXa active site.

PMID- 7721755
TI  - Regulation of integrin affinity states through an NPXY motif in the beta subunit
      cytoplasmic domain.
AB  - The ligand binding affinities of the integrins are regulated through their
      cytoplasmic domains. To identify specific residues that are involved in this
      process, we have generated mutants in the beta 1 and beta 3 tails and coexpressed
      them in Chinese hamster ovary cells with constitutively active alpha subunits.
      These alpha subunits are chimera of extra-cellular and transmembrane alpha IIb
      joined to the cytoplasmic domains of alpha 5, alpha 6A, or alpha 6B and confer an
      energy-dependent high affinity state when expressed in Chinese hamster ovary
      cells. The affinity state of these transfectants was determined by analyzing the
      binding of PAC1, an antibody that specifically recognizes the activated form of
      the reporter group, extracellular alpha IIb beta 3. We have identified point
      mutants in several areas of the beta tails, which result in a reduced ability to
      bind ligand. Complete abolition of PAC1 binding was obtained with mutants in an
      NPXY motif found in many integrin beta subunits and implicated in the
      internalization of other cell surface receptors. Similar effects on PAC1 binding
      were observed whether coexpression was with alpha chimera containing alpha 5,
      alpha 6A, or alpha 6B cytoplasmic sequences. These studies identify a novel role
      for the NPXY motif in the regulation of integrin binding affinity.

PMID- 7721756
TI  - A karyophilic protein forms a stable complex with cytoplasmic components prior to
      nuclear pore binding.
AB  - Targeting of karyophilic proteins to nuclear pores is known to require several
      cytoplasmic factors, including the nuclear location signal-binding protein. Using
      a digitonin-permeabilized cell-free transport assay, we have obtained a
      cytoplasmic fraction containing factors that specifically bind to karyophilic
      protein and support the nuclear binding step of the transport. Components in this
      fraction form a stable complex with the karyophile through interaction with
      nuclear location signal. Since this complex shows nuclear pore binding activity
      prior to nuclear entry in the absence of other cytosolic factors, we call it
      nuclear pore-targeting complex. It consists of karyophilic protein and four
      proteins of 54, 56, 66, and 90 kDa. In our reconstitution experiments, a complex
      with 54 and 90 kDa proteins is capable of targeting karyophiles to the nuclear
      pores.

PMID- 7721757
TI  - Editing of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR
      B pre-mRNA in vitro reveals site-selective adenosine to inosine conversion.
AB  - In neurons of the mammalian brain primary transcripts of genes encoding subunits
      of glutamate receptor channels can undergo RNA editing, leading to altered
      properties of the transmitter-activated channel. Editing of these transcripts is
      a nuclear process that targets specific adenosines and requires a double-stranded
      RNA structure configured from complementary exonic and intronic sequences. We
      show here that the two independent editing sites in alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid receptor GluR-B pre-mRNA are edited with
      positional accuracy by nuclear extract from HeLa cells. Nucleotide analysis by
      thin layer chromatography of the edited RNA sequences revealed selective
      adenosine to inosine conversion, most likely reflecting the participation of
      double-stranded RNA adenosine deaminase. Our results predict the presence of
      inosine-containing codons in other mammalian mRNAs.

PMID- 7721758
TI  - Structure and function of several anti-dansyl chimeric antibodies formed by
      domain interchanges between human IgM and mouse IgG2b.
AB  - Two pairs of chimeric, domain-switched immunoglobulins with identical murine,
      anti-dansyl (5-dimethylaminonaphthalene-1-sulfonyl) variable domains have been
      generated, employing as parent antibodies a human IgM and a mouse IgG2b. The
      first pair of chimeric antibodies mu mu gamma mu and gamma gamma mu gamma was
      generated by switching the C mu 3 and C gamma 2 domains between IgM and IgG2b.
      The second pair of chimeras mu mu gamma gamma and gamma gamma mu mu were formed
      by switching both C mu 3 and C mu 4 with C gamma 2 and C gamma 3. SDS
      polyacrylamide gel electrophoresis and analytical ultracentrifugation showed that
      over half (57 and 71%) of the two chimeric antibodies possessing the C mu 4
      domain and tail piece formed disulfide-linked IgM-like polymers. In contrast, the
      two chimeric antibodies lacking the C mu 4 domain were almost entirely monomeric.
      Both monomeric chimeras had reduced ability to activate complement. The chimera
      gamma gamma mu gamma had no activity under any of the assay conditions, whereas
      mu mu gamma gamma caused only a small amount of cell lysis but was fully active
      in consuming complement at 4 degrees C. The polymeric chimera gamma gamma mu mu
      was much less active than IgM, bound C1 weakly and caused some cell lysis but
      consumed little complement with soluble antigen. The polymeric chimera mu mu
      gamma mu bound C1 strongly and was the most active antibody in all assays, even
      more active than the parental IgG2b and IgM antibodies; it was the only antibody
      that exhibited antigen-independent activity. The results suggest that C mu 3
      alone does not constitute the complement binding site in IgM but requires both C
      mu 1-2 and C mu 4 for full activity.

PMID- 7721759
TI  - Chylomicron metabolism in normal, cholesterol-fed, and Watanabe heritable
      hyperlipidemic rabbits. Saturation of the sequestration step of the remnant
      clearance pathway.
AB  - The plasma clearance of radiolabeled chylomicrons was compared in normal,
      cholesterol-fed, and Watanabe heritable hyperlipidemic (WHHL) rabbits.
      Chylomicron clearance was rapid in normal rabbits but was significantly retarded
      in cholesterol-fed and WHHL rabbits. At 40 min after the injection of
      chylomicrons, 14-17% of the injected dose remained in the plasma of normal
      rabbits, whereas approximately 40-50% of the injected dose remained in the plasma
      of cholesterol-fed and WHHL rabbits. The differences were reflected in the
      reduced plasma clearance by the liver and bone marrow of the cholesterol-fed and
      WHHL rabbits. The hyperlipidemic rabbits expressed normal levels of low density
      lipoprotein (LDL) receptor-related protein/alpha 2-macroglobulin receptor in the
      liver. In contrast, the hepatic levels of LDL receptors were lower in
      hyperlipidemic rabbits; as expected, they were significantly lower in WHHL
      rabbits compared with normal and cholesterol-fed rabbits. Furthermore, it was
      demonstrated that lipoproteins accumulating in the plasma of the hyperlipidemic
      rabbits competed for and retarded the clearance of chylomicrons from the plasma.
      Competition was demonstrated by cross-circulation of normal and cholesterol-fed
      or normal and WHHL rabbits, in which the rapid influx of plasma containing the
      accumulated plasma lipoproteins from cholesterol-fed or WHHL rabbits was shown to
      impair the uptake of chylomicrons by the liver and bone marrow of normal rabbits.
      These observations were extended by infusing isolated lipoproteins into normal
      rabbits. The rabbit d < 1.02 g/ml (remnant) fraction and the canine cholesterol
      rich high density lipoproteins (HDL) with apolipoprotein E (HDLc) inhibited
      chylomicron clearance, whereas human LDL and HDL from humans and rabbits did not.
      We conclude that the low LDL receptor activity in the cholesterol-fed and WHHL
      rabbits may contribute, at least in part, to the impaired clearance by decreasing
      remnant uptake and causing the accumulation of chylomicron and/or very low
      density lipoprotein remnants. The accumulated remnant lipoproteins then compete
      for and saturate the mechanism responsible for the initial rapid clearance of
      chylomicrons from the plasma. We speculate that saturation of the initial rapid
      clearance may occur at the sequestration step, which involves the binding of
      remnants to heparan sulfate proteoglycans in the space of Disse.

PMID- 7721761
TI  - A thermostable mutation located at the hydrophobic core of alpha 1-antitrypsin
      suppresses the folding defect of the Z-type variant.
AB  - A thermostable mutation, F51L, at the hydrophobic core of human alpha 1
      antitrypsin (alpha 1AT) increased the conformational stability of the molecule by
      decreasing the unfolding rate significantly without altering the refolding rate.
      The mutation specifically influenced the transition between the native state and
      a compact intermediate, which retained approximately 70% of the far-UV CD signal,
      but which had most of the fluorescence signal already dequenched. The mutant
      alpha 1AT protein was more resistant than the wild-type protein to the insertion
      of the tetradecapeptide mimicking the sequence of the reactive center loop,
      indicating that the mutation increases the closing of the central beta-sheet, the
      A-sheet, in the native state. The F51L mutation enhanced the folding efficiency
      of the Z-type (E342K) genetic variation, which causes aggregation of the molecule
      in the liver. It has been shown previously that the aggregation of the Z protein
      occurs via loop-sheet polymerization, in which the reactive center loop of one
      molecule is inserted into the opening of the A-sheet of another molecule. Our
      results strongly suggest that the hydrophobic core of alpha 1AT regulates the
      opening-closing of the A-sheet and that certain genetic variations that cause
      opening of the A-sheet can be corrected by inserting an additional stable
      mutation into the hydrophobic core.

PMID- 7721760
TI  - Role of apolipoprotein A-I in cholesterol transfer between lipoproteins. Evidence
      for involvement of specific apoA-I domains.
AB  - A series of monoclonal antibodies against epitopes spanning different domains of
      apoA-I have been tested for their effects on unesterified cholesterol transfer
      between low density lipoprotein (LDL) and well-defined homogenous lipoproteins
      reconstituted with phosphatidylcholine, cholesterol, and apoA-I (LpA-I).
      Antibodies 2G11 (reacting between residues 25 and 110), A05 (residues 25-82), A03
      (residues 135-140), A44 and r5G9 (residues 149-186), and 4A12 (residues 173-205)
      significantly inhibit cholesterol transfer from LDL to Lp2A-I while they enhance
      transfer in the opposite direction, thus causing an increased net transfer to
      LDL. Most of these monoclonal antibodies (mAbs) also enhance phospholipid
      transfer to LDL but in a lesser and variable proportion relative to cholesterol.
      Their epitopes are mainly contained within domains that are predicted to be
      amphipathic alpha-helices. In contrast, mAbs 4H1 (residues 2-8), 3G10 (residues
      96-121), and 5F6 (residues 116-141) have little or no effect on either
      cholesterol or phospholipid transfer, and the epitopes for these three mAbs have
      been shown in earlier studies to be structurally and functionally related. Their
      immunoreactivity responds similarly to variation in lipoprotein cholesterol
      content, and the antibodies binding to these sites compete with one another and
      have similar effects on the cholesterol esterification reaction. Thus, the
      current results are compatible with the hypothesis that they form an integrated
      domain with a common function in cholesterol metabolism, possibly as part of a
      hinge domain. Most mAbs were found to increase significantly the alpha-helicity
      of apoA-I in the Lp2A-I immunecomplexes, suggesting that they may increase the
      stability of the lipid-bound apoA-I. However, not unexpectedly, there is no
      correlation between the effects of mAbs on alpha-helicity and their effects on
      cholesterol or phospholipid transfer since each mAb has a discrete effect on
      these transfers. These studies demonstrate the specificity of LpA-I particles in
      cholesterol transport and document the existence of apoA-I domains with different
      functions in cholesterol transport.

PMID- 7721762
TI  - Random substitution of large parts of the propeptide of yeast proteinase A.
AB  - The yeast aspartic protease, proteinase A, has a 54 amino-acid propeptide, which
      is removed during activation of the zymogen in the vacuole. Apart from being
      involved inhibition/activation, the propeptide has been shown to be essential for
      formation of a stable active enzyme (van den Hazel, H. B., Kielland-Brandt, M.
      C., and Winther, J. R. (1993) J. Biol. Chem. 268, 18002-18007). We have
      investigated the sequence requirements for function of the propeptide. The N
      terminal half and the C-terminal half of the propeptide were replaced by random
      sequences at the genetic level, and collections of the mutants were subjected to
      a colony screen for ones exhibiting activity. A high frequency (around 1%) of
      active constructs was found, which indicates a very high tolerance for mutations
      in the propeptide. Thirty-nine functional mutant forms containing random sequence
      at either the N- or C-terminal half of the propeptide were characterized.
      Comparison of the propeptides of the active constructs suggests that a particular
      lysine residue is important for efficient biosynthesis of proteinase A.

PMID- 7721763
TI  - Genetic and molecular characterization of a gene encoding a wide specificity
      purine permease of Aspergillus nidulans reveals a novel family of transporters
      conserved in prokaryotes and eukaryotes.
AB  - In Aspergillus nidulans, loss-of-function mutations in the uapA and azgA genes,
      encoding the major uric acid-xanthine and hypoxanthine-adenine-guanine permeases,
      respectively, result in impaired utilization of these purines as sole nitrogen
      sources. The residual growth of the mutant strains is due to the activity of a
      broad specificity purine permease. We have identified uapC, the gene coding for
      this third permease through the isolation of both gain-of-function and loss-of
      function mutations. Uptake studies with wild-type and mutant strains confirmed
      the genetic analysis and showed that the UapC protein contributes 30% and 8-10%
      to uric acid and hypoxanthine transport rates, respectively. The uapC gene was
      cloned, its expression studied, its sequence and transcript map established, and
      the sequence of its putative product analyzed. uapC message accumulation is: (i)
      weakly induced by 2-thiouric acid; (ii) repressed by ammonium; (iii) dependent on
      functional uaY and areA regulatory gene products (mediating uric acid induction
      and nitrogen metabolite repression, respectively); (iv) increased by uapC gain-of
      function mutations which specifically, but partially, suppress a leucine to
      valine mutation in the zinc finger of the protein coded by the areA gene. The
      putative uapC gene product is a highly hydrophobic protein of 580 amino acids
      (M(r) = 61,251) including 12-14 putative transmembrane segments. The UapC protein
      is highly similar (58% identity) to the UapA permease and significantly similar
      (23-34% identity) to a number of bacterial transporters. Comparisons of the
      sequences and hydropathy profiles of members of this novel family of transporters
      yield insights into their structure, functionally important residues, and
      possible evolutionary relationships.

PMID- 7721764
TI  - Activation of natural killer cell migration by leukocyte integrin-binding peptide
      from intracellular adhesion molecule-2 (ICAM-2).
AB  - Intracellular adhesion molecule-2 (ICAM-2), one of the ligands of CD11a/CD18 (LFA
      1), is mainly expressed on endothelial and hematopoietic cells. The biological
      significance of ICAM-2 has remained unclear. Previous findings have shown that a
      peptide from ICAM-2, spanning residues 21-42 from the first immunoglobulin
      domain, enhances natural killer (NK) cell cytotoxicity and induces T cell
      aggregation. We have now studied the effect of the same ICAM-2 peptide on NK cell
      migration in the Boyden chamber assay. The peptide significantly increased NK
      cell migration up to 215 +/- 21%, as compared to migration of control cells
      (100%), and the induction was inhibited by anti-CD11a monoclonal antibodies. The
      ICAM-2 peptide also induced polymerization of F-actin at the leading edge of
      migratory NK cells. Cross-linking of CD11a/CD18 receptors with anti-CD11a or anti
      CD18 monoclonal antibodies and secondary antibodies resulted in receptor
      recycling, increased migration, and actin polymerization, but led to slight
      inhibition of cytotoxicity. The ICAM-2 peptide did not induce such a receptor
      recycling. Phosphotyrosine immunoblotting experiments showed that the ICAM-2
      peptide increased the phosphorylation of 150- and 35-kDa proteins. During cross
      linking with antibodies, only the 150-kDa protein showed increased
      phosphorylation. The results show that depending on the type of CD11a/CD18
      receptor ligation different kinds of signals are transduced in NK cells. These
      signals may either trigger only locomotion, or both locomotion and cytotoxicity.
      Based on these findings, a major function for ICAM-2 on endothelium may be
      triggering of migration of adhering leukocytes.

PMID- 7721765
TI  - The RNA polymerase I promoter-activating factor CPBF is functionally and
      immunologically related to the basic helix-loop-helix-zipper DNA-binding protein
      USF.
AB  - Analysis of the core promoter sequence of the mammalian ribosomal RNA genes
      revealed an E-box-like sequence (CACGCTG) to which the upstream stimulatory
      factor (USF) binds. Because the core promoter binding factor (CPBF) binds
      specifically to the core promoter sequence of the ribosomal RNA gene (Liu, Z.,
      and Jacob, S. T. (1994) J. Biol. Chem. 269, 16618-16626) and resembles USF in
      some respects, we explored the potential relationship between USF and CPBF.
      Competition electrophoretic mobility shift assay using labeled core promoter
      probe and several unlabeled competitor oligonucleotides showed that USF can
      indeed bind to the core promoter and that only those oligonucleotides with an E
      box sequence could compete in the promoter-protein complex formation
      characteristic of CPBF. This complex formation was thermostable, a unique
      property of USF. Furthermore, antibodies raised against USF cross-reacted with
      the 44-kDa component of rat CPBF. To prove further the relationship between CPBF
      and USF, we examined the effects of the unlabeled USF and ribosomal gene core
      promoter oligonucleotides on polymerase (pol) I and pol II transcription. Both
      oligonucleotides inhibited rDNA transcription as well as transcription from the
      adenovirus major late promoter. Only the oligonucleotides that contain the E-box
      sequence competed in the transcription. These data indicate that the promoter
      sequence of mammalian ribosomal RNA gene contains an USF-binding site, that the
      44-kDa polypeptide of CPBF is related to the 44/43-kDa polypeptide of human USF,
      and that USF or USF-related protein can transactivate both pol I and pol II
      promoters.

PMID- 7721766
TI  - Endoplasmic reticulum-mediated quality control of type I collagen production by
      cells from osteogenesis imperfecta patients with mutations in the pro alpha 1 (I)
      chain carboxyl-terminal propeptide which impair subunit assembly.
AB  - A heterozygous single base change in exon 49 of COL1A1, which converted the codon
      for pro alpha 1(I) carboxyl-terminal propeptide residue 94 from tryptophan (TGG)
      to cysteine (TGT) was identified in a baby with lethal osteogenesis imperfecta
      (OI64). The C-propeptide mutations in OI64 and in another lethal osteogenesis
      imperfecta cell strain (OI26), which has a frameshift mutation altering the
      sequence of the carboxyl-terminal half of the propeptide (Bateman, J. F.,
      Lamande, S. R., Dahl, H.-H. M., Chan, D., Mascara, T. and Cole, W. G. (1989) J.
      Biol. Chem. 264, 10960-10964), disturbed procollagen folding and retarded the
      formation of disulfide-linked trimers. Although assembly was delayed, the
      presence of slowly migrating, overmodified alpha 1(I) and alpha 2(I) chains
      indicated that mutant pro alpha 1(I) could associate with normal pro alpha 1(I)
      and pro alpha 2(I) to form pepsin-resistant triple-helical molecules, a
      proportion of which were secreted. Further evidence of the aberrant folding of
      mutant procollagen in OI64 and OI26 was provided by experiments demonstrating
      that the endoplasmic reticulum resident molecular chaperone BiP, which binds to
      malfolded proteins, was specifically bound to type I procollagen and was
      coimmunoprecipitated in the osteogenesis imperfecta cells but not control cells.
      Experiments with brefeldin A, which inhibits protein export from the endoplasmic
      reticulum, demonstrated that unassembled mutant pro alpha 1(I) chains were
      selectively degraded within the endoplasmic reticulum resulting in reduced
      collagen production by the osteogenesis imperfecta cells. This biosynthetic
      deficiency was reflected in the inability of OI64 and OI26 cells to produce a
      substantial in vitro collagenous matrix when grown in the continuous presence of
      ascorbic acid to allow collagen matrix formation. Both these carboxyl-terminal
      propeptide mutants showed a marked reduction in collagen accumulation to 20% (or
      less) of control cultures, comparable to the reduced collagen content of tissues
      from OI26.

PMID- 7721767
TI  - Genetic analysis of the fluorescein isothiocyanate binding site of the yeast
      plasma membrane H(+)-ATPase.
AB  - The highly conserved motif of Saccharomyces cerevisiae H(+)-ATPase 474KGAP has
      been proposed to participate in the formation of the phosphorylated intermediate
      during the catalytic cycle (Portillo, F., and Serrano, R. (1988) EMBO J. 7, 1793
      1798). In addition, Lys-474 is the FITC binding site of the yeast enzyme
      (Portillo, F. and Serrano, R. (1989) Eur. J. Biochem. 186, 501-507). We have
      performed an intragenic suppressor analysis of the K474R mutation to identify the
      interacting regions involved in these functions. Random in vitro mutagenesis of
      the K474R allele resulted in seven suppressor (second-site) mutations. One
      mutation (V396I), located 18 residues away from the Asp-378 residue, which is
      phosphorylated during catalysis, is allele-specific. This provides genetic
      evidence of a direct interaction between the KGAP motif and the phosphorylation
      domain during the catalytic cycle. Three mutations (V484I, V484I/E485K, and
      E485K/E486K) are located near Lys-474 and may compense the structural alteration
      introduced by the K474R mutation. Two substitutions at the end of the predicted
      transmembrane stretch 2 (A165V and V169I/D170N) and another in the predicted ATP
      binding domain (P536L) may act as allele-nonspecific suppressors, as they are
      also able to suppress a mutation at the enzyme's carboxyl terminus.

PMID- 7721768
TI  - Deoxyhypusine synthase from rat testis: purification and characterization.
AB  - Deoxyhypusine synthase is the first enzyme involved in the post-translational
      formation of hypusine, a unique amino acid that occurs at one position in a
      single cellular protein, eukaryotic translation initiation factor 5A (eIF-5A).
      This NAD-dependent enzyme catalyzes the formation of deoxyhypusine by transfer of
      the butylamine portion of spermidine to the epsilon-amino group of a specific
      lysine residue in the eIF-5A precursor. Its purification from rat testis was
      accomplished by ammonium sulfate fractionation and successive ion-exchange
      chromatographic steps, followed by chromatofocusing on a hydrophilic resin (Mono
      P). A pI of 4.7 was determined by isoelectric focusing. Amino acid sequences of
      five tryptic peptides of the pure enzyme did not correspond to any sequences in
      the protein data banks. The enzyme migrates as a single band on SDS
      polyacrylamide gel electrophoresis with an apparent monomer molecular mass of
      approximately 42,000 Da. Matrix-assisted laser desorption mass spectrometry gave
      a monomer mass of 40,800 Da. There is evidence, however, that the active enzyme
      exists as a tetramer of this subunit. Rabbit polyclonal antibodies to the 42-kDa
      protein precipitated deoxyhypusine synthase activity. The enzyme shows a strict
      specificity for NAD. Purified deoxyhypusine synthase catalyzes the overall
      synthesis of deoxyhypusine and, in the absence of the eIF-5A precursor, catalyzes
      the cleavage of spermidine.

PMID- 7721769
TI  - Agonist-induced loss of ligand binding is correlated with phosphorylation of
      cAR1, a G protein-coupled chemoattractant receptor from Dictyostelium.
AB  - The parallel agonist-induced phosphorylation, alteration in electrophoretic
      mobility, and loss of ligand binding of a guanine nucleotide-binding regulatory
      protein (G protein)-coupled chemoattractant receptor from Dictyostelium (cAR1)
      depend upon a cluster of five C-terminal domain serine residues (Caterina, M. J.,
      Hereld, D., and Devreotes, P.N. (1995) J. Biol. Chem. 270, 4418-4423). Analysis
      of mutants lacking combinations of these serines revealed that either Ser303 or
      Ser304 is required; mutants lacking both serines are defective in all of these
      responses. Interestingly, several mutants, including those substituted at only
      Ser299, Ser302, or Ser303 or at non-serine positions within the third cytoplasmic
      loop, displayed an unstable mobility shift; the alteration was rapidly reversed
      upon cAMP removal. These mutants also exhibited subnormal extents of loss of
      ligand binding, which is assessed after removal of the ligand. For the wild-type
      receptor, we found that the stability of phosphorylation depends upon the
      concentration and duration of agonist pretreatment. This suggests that, following
      phosphorylation of Ser303 or Ser304, cAR1 undergoes a further transition (EC50
      approximately 140 nM, t 1/2 approximately 4 min) to a relatively phosphatase
      resistant state. We used this insight to show that, under all conditions tested,
      the extent of loss of binding is correlated with the fraction of cAR1 in the
      altered mobility form. We discuss possible relationships between cAR1
      phosphorylation and loss of ligand binding.

PMID- 7721770
TI  - Measurements of CO geminate recombination in cytochromes P450 and P420.
AB  - The kinetics of CO geminate recombination in cytochrome P450cam are studied at
      room temperature subsequent to laser photolysis. The geminate rebinding kinetics
      of P450 are strongly affected by the presence of the camphor substrate. We
      observe a approximately 2% geminate yield for substrate-bound P450 and a 90%
      geminate yield when the substrate is absent. The drastic difference in the
      geminate kinetics suggests that the presence of camphor significantly alters the
      CO rebinding and escape rates by modifying the heme pocket environment. Two
      geminate phases and two bimolecular rebinding phases in the substrate free
      protein were observed, which could arise from slowly interconverting protein
      conformations. When the temperature or the viscosity of the solution is changed,
      the fast geminate rate remains the same, whereas the slow geminate rate and the
      two bimolecular rates change significantly. The geminate rebinding yield of
      substrate-free P420 is smaller than that of substrate free P450, but its geminate
      rebinding rate is faster. This demonstrates that in the absence of substrate, CO
      escapes from the pocket of P420 much more rapidly than from P450 and suggests
      that the distal pocket environment is altered in the P420 form.

PMID- 7721771
TI  - Tissue-type plasminogen activator (tPA) interacts with urokinase-type plasminogen
      activator (uPA) via tPA's lysine binding site. An explanation of the poor fibrin
      affinity of recombinant tPA/uPA chimeric molecules.
AB  - Differential scanning calorimetry was used to study the domain structure and
      intramolecular interactions of tPA/uPA chimeras. A high temperature transition
      centered near 90 degrees C was observed upon melting of the tPA/uPA chimera
      (amino acids 1-274 of tPA and 138-411 of uPA) and its variant lacking the finger
      and epidermal growth factor-like modules (residues 1-3 and 87-274 of tPA and 138
      411 of uPA). Since neither of the two parent plasminogen activators display such
      a stable structure, one may suggest that a new stabilizing intramolecular
      interaction occurs in the chimeras. We found that occupation of the lysine
      binding site of tPA by a lysine or arginine side chain from the urokinase moiety
      is responsible for the high temperature transition as well as for the failure of
      the chimeras to exhibit the expected fibrin binding properties. All uPA species,
      single- and two-chain high molecular weight uPA (Pro-Uk and HMW-Uk) and two-chain
      low molecular weight uPA (LMW-Uk), interact intermolecularly with tPA and its
      kringle-containing derivatives. This intermolecular interaction was strongly
      inhibited by epsilon-aminocaproic acid indicating that the lysine binding site of
      tPA is involved. The binding of uPA with the fluorescein-labeled A-chain of tPA,
      registered by changes in fluorescence anisotropy, was estimated to have a Kd
      range of 1-7 microM. The interaction of tPA with uPA determined by solid-phase
      assays appeared to be tighter, with a Kd range of 50-300 nM. Two synthetic
      peptides, with and without carboxyl-terminal lysine, corresponding to urokinase
      residues 144-158 and 144-157, were approximately 100-fold more potent than
      epsilon-aminocaproic acid with respect to inhibition of the tPA-uPA interaction,
      indicating that the tPA binding site on urokinase is located within this
      sequence, close to the activation site Lys158-Ile159. The discovered
      intermolecular interaction may be related to the reported synergistic effect of
      simultaneous administration of these two plasminogen activators.

PMID- 7721773
TI  - Purification, partial characterization, and cloning of nitric oxide-carrying heme
      proteins (nitrophorins) from salivary glands of the blood-sucking insect Rhodnius
      prolixus.
AB  - Four nitric oxide (NO)-carrying proteins have been isolated from salivary glands
      of the blood-sucking insect Rhodnius prolixus. These have been given the
      collective name "nitrophorins," and individual proteins are designated NP1-NP4 in
      order of their relative abundance in the glands. All four reversibly bind NO;
      spectral shifts associated with NO binding indicate the interaction of NO with an
      Fe(III) heme. Physical properties, amino acid composition, and amino-terminal
      sequences of the nitrophorins are reported. The most abundant nitrophorin was
      cloned, and its sequence was determined.

PMID- 7721772
TI  - Cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene is the
      committed step of taxol biosynthesis in Pacific yew.
AB  - The biosynthesis of taxol (paclitaxel) and related taxoids in Pacific yew (Taxus
      brevifolia) is thought to involve the cyclization of geranylgeranyl diphosphate
      to a taxadiene followed by extensive oxygenation of this diterpene olefin
      intermediate. A cell-free preparation from sapling yew stems catalyzed the
      conversion of [1-3H]geranylgeranyl diphosphate to a cyclic diterpene olefin that,
      when incubated with stem sections, was converted in good radiochemical yield to
      several highly functionalized taxanes, including 10-deacetyl baccatin III and
      taxol itself. Addition of the labeled olefin to a yew bark extract, followed by
      radiochemically guided fractionation, provided sufficient product to establish
      the structure as taxa-4(5),11(12)-diene by two-dimensional NMR spectroscopic
      methods. Therefore, the first dedicated step in taxol biosynthesis is the
      conversion of the universal diterpenoid precursor geranylgeranyl diphosphate to
      taxa-4(5),11(12)-diene, rather than to the 4(20),11(12)-diene isomer previously
      suggested on the basis of the abundance of taxoids with double bonds in these
      positions. The very common occurrence of taxane derivatives bearing the 4(20)-ene
      5-oxy functional grouping, and the lack of oxygenated derivatives bearing a 4(5)
      double bond, suggest that hydroxylation at C-5 of taxadiene with allylic
      rearrangement of the double bond is an early step in the conversion of this
      olefin intermediate to taxol.

PMID- 7721774
TI  - Isolation of the porcine heparin tetrasaccharides with glucuronate 2-O-sulfate.
      Heparinase cleaves glucuronate 2-O-sulfate-containing disaccharides in highly
      sulfated blocks in heparin.
AB  - Eleven tetrasaccharides were isolated from the repeating disaccharide region of
      porcine intestinal heparin after strong digestion with Flavobacterium heparinase.
      Their structures were determined by composition analysis, enzymatic analysis, and
      1H NMR spectroscopy. Nine of them have the common tetrasaccharide backbone, delta
      HexA alpha 1-4GlcN alpha 1-4IdoA alpha 1-4GlcN, where delta HexA and IdoA
      represent 4,5-unsaturated hexuronic acid and L-iduronic acid, respectively, and
      their structural variations are based upon the positions of sulfate groups. The
      nine compounds include one hexasulfated, three pentasulfated and five
      tetrasulfated compounds, and four of them have not been isolated previously as
      discrete structures. The other two of the 11 tetrasaccharides have the following
      hitherto unreported structures with novel glucuronate 2-O-sulfate at the internal
      position: delta HexA(2-sulfate) alpha 1- 4GlcN(N,6-disulfate) alpha 1-4GlcA(2
      sulfate) beta 1-4GlcN(N-sulfate) and delta HexA(2-sulfate) alpha 1-4GlcN(N,6
      disulfate) alpha 1-4GlcA(2-sulfate) beta 1-4GlcN(N,6-disulfate). Thus, 2-O
      sulfated glucuronate in the highly sulfated tetrasaccharide structures typical of
      heparin has been demonstrated. The former and the latter tetrasaccharides account
      for 0.31 and 0.32% (w/w) of the starting heparin, respectively. Their yield,
      however, is an underestimation, since these tetrasaccharide structures in longer
      sequences will be degraded by heparinase. Although the latter tetrasaccharide
      described above was unexpectedly cleaved by heparinase into two disaccharide
      units, the former was not degraded by the enzyme most likely due to the lack of
      the 6-O-sulfate group on the GlcN residue at the reducing terminus. The results
      indicate its capability of catalyzing both anti and syn elimination, a property
      shared by heparitinases I and II and chondroitinase ABC. Both tetrasaccharides
      were degraded into disaccharides by heparitinase II. Therefore, it is necessary
      to reevaluate the disaccharide composition of heparin/heparan sulfate or
      oligosaccharide structures, which were previously determined after heparinase or
      heparitinase II digestion. It is no longer possible to conclude that the 2-O
      sulfated unsaturated uronic acid residues obtained from heparin/heparan sulfate
      by lyase digestions are always derived from iduronate 2-O-sulfate residues in the
      original polymer. It is quite possible that the novel glucuronate 2-O-sulfate
      structure in the highly sulfated region of heparin is involved in some of the
      biological activities of heparin.

PMID- 7721775
TI  - Catalyzed thermal isomerization between previtamin D3 and vitamin D3 via beta
      cyclodextrin complexation.
AB  - To examine the effect of microenvironments on previtamin D3<==>vitamin D3
      isomerization, we have conducted kinetic studies of the reaction in an aqueous
      solution of beta-cyclodextrin. Our results showed that at 5 degrees C, the
      forward (k1) and reverse (k2) rate constants for previtamin D3<==>vitamin D3
      isomerization were increased by more than 40 and 600 times, respectively,
      compared with those in n-hexane (k1, 8.65 x 10(-6) versus 1.76 x 10(-7) s-1; k2,
      8.48 x 10(-6) versus 1.40 x 10(-8) s-1), the fastest rate of this isomerization
      ever reported at this temperature. Thermodynamic studies revealed that the
      equilibrium constant of the reaction was significantly reduced by more than 12
      fold when compared to that in n-hexane at 5 degrees C, and the percentage of
      vitamin D3 at equilibrium was increased as the temperature was increased in beta
      cyclodextrin. When complexed with beta-cyclodextrin, the previtamin D3<==>vitamin
      D3 isomerization became endothermic (delta H zero = 13.05 kJ mol-1) in contrast
      to being exothermic in other media. We propose that thermodynamically unfavorable
      cZc conformers of previtamin D3 are stabilized by beta-cyclodextrin, and thus the
      rate of the isomerization is increased. This conformation-controlled process may
      play an important role in the modulation of previtamin D3<==>vitamin D3 endocrine
      system in vivo such as in the sea urchin.

PMID- 7721776
TI  - Acceptor specificity of different length constructs of human recombinant alpha
      1,3/4-fucosyltransferases. Replacement of the stem region and the transmembrane
      domain of fucosyltransferase V by protein A results in an enzyme with GDP-fucose
      hydrolyzing activity.
AB  - The acceptor specificity of recombinant full-length, membrane-bound
      fucosyltransferases, expressed in COS-7 cells, and soluble, protein-A chimeric
      forms of alpha 1,3-fucosyltransferase (Fuc-T) III, Fuc-TIV, and Fuc-TV was
      analyzed toward a broad panel of oligosaccharide, glycolipid, and glycoprotein
      substrates. Our results on the full-length enzymes confirm and extend previous
      studies. However, chimeric Fuc-Ts showed increased activity toward glycoproteins,
      whereas chimeric Fuc-TIII and Fuc-TV had a decreased activity with
      glycosphingolipids, compared to the full-length enzymes. Unexpectedly, chimeric
      Fuc-TV exhibited a GDP-fucose hydrolyzing activity. In substrates with multiple
      acceptor sites, the preferred site of fucosylation was identified. Fuc-TIII and
      Fuc-TV catalyzed fucose transfer exclusively to OH-3 of glucose in lacto-N
      neotetraose and lacto-N-tetraose, respectively, as was demonstrated by 1H NMR
      spectroscopy. Thin layer chromatography immunostaining revealed that FucT-IV
      preferred the distal GlcNAc residue in nLc6Cer, whereas Fuc-TV preferred the
      proximal Gl-cNAc residue. Incubation of Fuc-TIV or Fuc-TV with VI3NeuAcnLc6Cer
      resulted in products with the sialyl-LewisX epitope as well as the VIM-2
      structure. To identify polar groups on acceptors that function in enzyme binding,
      deoxygenated substrate analogs were tested as acceptors. All three Fuc-Ts had an
      absolute requirement for a hydroxyl at C-6 of galactose in addition to the
      accepting hydroxyl at C-3 or C-4 of GlcNAc.

PMID- 7721777
TI  - Identification of the sorting signal motif within pro-opiomelanocortin for the
      regulated secretory pathway.
AB  - The NH2-terminal region of pro-opiomelanocortin (POMC) is highly conserved across
      species, having two disulfide bridges that cause the formation of an amphipathic
      hairpin loop structure between the 2nd and 3rd cysteine residues (Cys8 to Cys20).
      The role that the NH2-terminal region of pro-opiomelanocortin plays in acting as
      a molecular sorting signal for the regulated secretory pathway was investigated
      by using site-directed mutagenesis either to disrupt one or more of the disulfide
      bridges or to delete the amphipathic loop entirely. When POMC was expressed in
      Neuro-2a cells, ACTH immunoreactive material was localized in punctate secretory
      granules in the cell body and along the neurites, with heavy labeling at the
      tips. ACTH was secreted from these POMC-transfected cells in a regulated manner.
      Disruption of both disulfide bridges or the second disulfide bridge or removal of
      the amphipathic hairpin loop resulted in constitutive secretion of the mutant
      POMC from the cells and a lack of punctate secretory granule immunostaining
      within the cells. We have modeled the NH2-terminal POMC Cys8 to Cys20 domain and
      have identified it as an amphipathic loop containing four highly conserved
      hydrophobic and acidic amino acid residues (Asp10-Leu11-Glu14-Leu1). Thus the
      sorting signal for POMC to the regulated secretory pathway appears to be encoded
      by a specific conformational motif comprised of a 13-amino acid amphipathic loop
      structure stabilized by a disulfide bridge, located at the NH2 terminus of the
      molecule.

PMID- 7721778
TI  - A mammalian helix-loop-helix factor structurally related to the product of
      Drosophila proneural gene atonal is a positive transcriptional regulator
      expressed in the developing nervous system.
AB  - We report the molecular characterization of a mouse basic helix-loop-helix
      factor, designated MATH-1, structurally related to the product of the Drosophila
      proneural gene atonal. MATH-1 mRNA is first detected in the cranial ganglions and
      the dorsal part of the central nervous system on embryonic day 9.5 (E9.5). From
      E10.5 onward, prominent expression of MATH-1 continues in the dorsal part of the
      central nervous system but becomes restricted to the external granular layer of
      the cerebellum by E18 and is undetectable in the adult nervous system. MATH-1
      activates E box-dependent transcription in collaboration with E47, but the
      activity is completely antagonized by the negative regulator of neurogenesis HES
      1. These results suggest that MATH-1 may be a target of HES-1 and play a role in
      the differentiation of subsets of neural cells by activating E box-dependent
      transcription.

PMID- 7721779
TI  - The essential transcription factor, Mcm1, is a downstream target of Sln1, a yeast
      "two-component" regulator.
AB  - In a search for mutants exhibiting altered activity of the yeast transcription
      factor, Mcm1, we have identified the SLN1 gene, whose product is highly related
      to bacterial two-component sensor-regulator proteins. sln1 alleles identified in
      our screen increased Mcm1p-mediated transcriptional activation, while deletion of
      the SLN1 locus severely reduced Mcm1p activity. Our data establish that Mcm1p is
      a downstream target of the Sln1 signaling pathway. Yeast Sln1p was recently shown
      to be involved in osmoregulation and to depend on the Hog1 MAP kinase (Maeda, T.,
      Wurgler-Murphy, S., and Saito, H. (1994) Nature 369, 242-245). We show that SLN1
      mediated regulation of Mcm1p activity is independent of the Hog1 MAP kinase, and
      suggest that the role of SLN1 is not restricted to osmoregulation.

PMID- 7721780
TI  - DNA looping by Saccharomyces cerevisiae high mobility group proteins NHP6A/B.
      Consequences for nucleoprotein complex assembly and chromatin condensation.
AB  - The formation of higher order protein.DNA structures often requires bending of
      DNA strands between specific sites, a process that can be facilitated by the
      action of nonspecific DNA-binding proteins which serve as assembly factors. A
      model for this activity is the formation of the invertasome, an intermediate
      structure created in the Hin-mediated site-specific DNA inversion reaction, which
      is stimulated by the prokaryotic nucleoid-associated protein HU. Previously, we
      have shown that the mammalian HMG1/2 proteins substitute for HU in this system
      and display efficient DNA wrapping activity in vitro. In the present work, we
      isolate the primary sources of assembly factor activity in Saccharomyces
      cerevisiae, as measured by the ability to stimulate invertasome formation, and
      show that these are the previously identified NHP6A/B proteins. NHP6A/B have
      comparable or greater activity in DNA binding, bending, and supercoiling with
      respect to HU and HMG1 and appear to form more stable protein.DNA complexes. In
      addition, expression of NHP6A in mutant Escherichia coli cells lacking HU and Fis
      restores normal morphological appearance to these cells, specifically in nucleoid
      condensation and segregation. From these data we predict diverse architectural
      roles for NHP6A/B in manipulating chromosome structure and promoting the assembly
      of multicomponent protein.DNA complexes.

PMID- 7721781
TI  - A haploid expressed gene cluster exists as a single chromatin domain in human
      sperm.
AB  - Mammalian spermiogenesis is marked by the initial disruption of the nuclear
      histone-DNA complex by the transition proteins for ultimate replacement with
      protamines. The genes for three of these low molecular weight basic nuclear
      proteins exist as a single linear array of PRM1, PRM2, and TNP2 on human
      chromosome 16p13.2. To begin to address the mechanism governing their
      transcriptional potentiation, a region of approximately 40 kilo-bases of the
      human genome encompassing these genes was introduced into the germ line of mice.
      Fluorescence in situ hybridization and Southern analysis showed that this segment
      of the human genome integrated into independent chromosomal sites while
      maintaining its fidelity. Transcript analysis demonstrated that the expression of
      the endogenous mouse protamine Prm1 and Prm2 genes as well as the mouse
      transition protein Tnp2 gene were expressed along with their human transgene
      counterparts. The pattern of expression of these transgenic human genes within
      this multigenic cluster faithfully represented that observed in vivo. In
      addition, all members of this transgenic gene cluster were expressed in
      proportions similar to those in human testis. Copy number-dependent and position
      independent expression of the transgenic construct demonstrated that the
      corresponding biological locus was contained within this segment of the human
      genome. Furthermore, DNase I sensitivity established that in sperm the human PRM1
      ->PRM2-->TNP2 genic domain was contained as an approximately 28.5-kilobase
      contiguous segment bounded by an array of nuclear matrix associated topoisomerase
      II consensus sites. This is the first description of a multigenic male gamete
      specific domain as a fundamental gene regulatory unit. A model of haploid
      specific gene determination is presented.

PMID- 7721782
TI  - Myb and Ets proteins cooperate to transactivate an early myeloid gene.
AB  - The earliest progenitor cell committed to the granulocyte/monocyte developmental
      pathway can be identified by the appearance of a 150-kDa glycoprotein on the cell
      surface (CD13/aminopeptidase N (CD13/APN), EC 3.4.11.2). A 455-base pair genomic
      fragment from the CD13/APN gene containing a Myb consensus-binding site as well
      as three potential Ets-binding sites was found to regulate tissue-appropriate
      expression of reporter genes in hematopoietic cell lines. Transactivation
      experiments with plasmids expressing either a full-length or truncated Myb
      protein and the full-length Ets-1 or Ets-2 protein demonstrated that these
      proteins cooperate to positively regulate CD13/APN gene expression. This
      cooperation is synergistic, as levels of transcriptional activity produced by Myb
      and Ets in combination were higher than those expected from a purely additive
      effect. Mutation of the Myb consensus-binding site completely abolished CD13/APN
      promoter activity in myeloid cells. Introduction of a dominant interfering Myb
      allele disrupted the ability of endogenous c-Myb in myeloid cells to
      transactivate the CD13/APN construct. Other myeloid cell-expressed Ets family
      members (PU.1, Fli-1, and Elf-1) failed to produce a cooperative transactivating
      effect when combined with the Myb expression construct. These data contrast with
      previous studies indicating that full-length c-Myb is unable to positively
      cooperate with Ets proteins in the regulation of myeloid genes. Because intact c
      Myb and Ets-2 proteins, both endogenously expressed in myeloid cells, act
      synergistically to transactivate the CD13/APN promoter, this gene may represent a
      physiological target for dissection of the roles of these transcription factors
      in normal and malignant myelopoiesis.

PMID- 7721783
TI  - Phosphorylation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, by
      casein kinase I in vitro and in vivo.
AB  - DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, M(r) = 32,000) is a potent
      inhibitor of protein phosphatase-1 when it is phosphorylated on Thr-34 by cAMP
      dependent protein kinase. DARPP-32 is highly enriched in some specific cell
      populations such as striatonigral neurons and choroid plexus epithelial cells.
      Here we show that recombinant rat DARPP-32 is phosphorylated by casein kinase I
      on seryl residues to a stoichiometry of approximately 2 mol of phosphate/mol of
      protein. DARPP-32 is one of the best known substrates for casein kinase I (Km =
      3.4 +/- 0.3 microM), whereas the homologous phosphatase-1 inhibitor, inhibitor-1,
      is not. Phosphorylation of DARPP-32 by casein kinase I does not alter its ability
      to inhibit protein phosphatase-1. Residues phosphorylated by casein kinase I were
      identified as Ser-137 and Ser-189 by site-directed mutagenesis and by protein
      sequencing. Ser-137 and the preceding stretch of 16-18 acidic residues are
      conserved in DARPP-32 among all species examined, whereas Ser-189 is not.
      Phosphorylation of Ser-137 induces an unusual increase in DARPP-32
      electrophoretic mobility in polyacrylamide gels in the presence of SDS. In
      striatonigral neurons, DARPP-32 is phosphorylated on Ser-137 and the
      stoichiometry of phosphorylation on this residue in vivo appears to be higher in
      the substantia nigra (axon terminals) than in the striatum (soma and dendrites).
      These results indicate that casein kinase I is highly active in striatonigral
      neurons in which it may play important roles, including in protein phosphatase-1
      modulation via phosphorylation of DARPP-32.

PMID- 7721784
TI  - Identification of a discrete region of the G protein gamma subunit conferring
      selectivity in beta gamma complex formation.
AB  - The identification of multiple G protein beta and gamma subunit subtypes suggests
      a potential diversity of beta gamma heterodimers, which may contribute to the
      specificity of signal transduction between receptors and effectors. The assembly
      of beta and gamma subtypes is selective. For example, gamma 1 can assemble with
      beta 1 but not with beta 2, whereas gamma 2 assembles with both beta isoforms. To
      identify the structural features of the beta and gamma subunits governing
      selectivity in heterodimer assembly, a series of nonisoprenylated chimeras of
      gamma 1 and gamma 2 was constructed, and their interaction with beta 1 and beta 2
      was assessed by their ability to direct beta expression to the cytosol in
      cotransfected COS cells. All of the gamma 1/gamma 2 chimeras were capable of
      interacting with beta 1 as judged by the cotransfection assay. Chimeras
      containing gamma 2 sequence near the middle of the molecule between two conserved
      sequence motifs were capable of interacting as well with beta 2. Among 12
      divergent residues in this region, it was found that replacement of three
      consecutive amino acids in gamma 1, Glu-Glu-Phe (residues 38-40), with the three
      corresponding amino acids of gamma 2, Ala-Asp-Leu (residues 35-37), conferred the
      ability to assemble with beta 2. The reciprocal chimera containing Glu-Glu-Phe in
      the context of gamma 2 failed to assemble with beta 2. The last residue of this
      triplet is occupied by a leucine in all known mammalian gamma subunits except
      gamma 1 and appears to be a key determinant of the ability of a gamma subunit to
      assemble with beta 2. This locus maps to a region of predicted alpha-helical
      structure in the gamma subunit, likely to represent a point of physical contact
      with the beta subunit.

PMID- 7721785
TI  - Topology of the Na,K-ATPase. Evidence for externalization of a labile
      transmembrane structure during heating.
AB  - The topological organization of the Na,K-ATPase alpha subunit is controversial.
      Detection of extracellular proteolytic cleavage sites would help define the
      topology, and so attempts were made to find conditions and proteases that would
      permit digestion of Na,K-ATPase in sealed right-side-out vesicles from renal
      medulla. The beta subunit is predominantly extracellular and could mask the
      surface of the alpha subunit. Most of the tested proteases cleaved beta, and some
      digested it extensively. However, without further disruption of structure, there
      was still no digestion of the alpha subunit. Reduction (at 50 degrees C) of
      disulfide bonds that might stabilize the beta subunit fragments, or heating alone
      at 55 degrees C, permitted tryptic digestion of alpha at a site close to the C
      terminus, while simultaneously increasing digestion of beta. A 90-kDa N-terminal
      fragment of alpha was recovered, but the C-terminal fragment was further
      digested. Heating and reduction resulted in the extracellular exposure of a
      protein kinase A phosphorylation site, Ser-938, and the C terminus, both of which
      have been proposed to be located on the intracellular surface. At the same time,
      access to a distant protein kinase C phosphorylation site was not increased. The
      data suggest that the harsh treatment simultaneously resulted in alteration of
      the beta subunit and the extrusion of a segment of alpha that normally spans the
      membrane, without causing complete denaturation or opening the sealed vesicles.
      Preincubation with Rb+ was protective, consistent with prior evidence that it
      stabilizes the protein segments in the C-terminal third of alpha. We conclude
      that this portion of the alpha subunit contains a transmembrane structure with
      unique lability to heating.

PMID- 7721786
TI  - Receptor for interleukin 13. Interaction with interleukin 4 by a mechanism that
      does not involve the common gamma chain shared by receptors for interleukins 2,
      4, 7, 9, and 15.
AB  - Interleukin 13 (IL-13) shares many biological properties with IL-4, and although
      the receptor for IL-4 (IL-4R) has been characterized, the expression and
      structure of IL-13 receptor are unknown. We report here that human renal cell
      carcinoma (RCC) cells express large numbers of functional IL-13R. Human B
      lymphocytes and monocytes expressed a very small number of IL-13R, while resting
      or activated human T cells expressed little or no IL-13R. IL-4 did not compete
      for IL-13 binding, while IL-13 competed for IL-4 binding, even though IL-4R and
      IL-13R are structurally distinct on human RCC cells. IL-13 cross-linked with one
      major protein that is similar in size to the gamma c subunit of IL-2, -4, -7, -9,
      and -15 receptors but was not recognized by anti-gamma c or anti-IL-4R
      antibodies. IL-4, on the other hand, cross-linked with two major proteins, the
      smaller of which appears to be similar in size to IL-13R and gamma c, but (like
      the IL-13R) it did not react with anti-gamma c antibody. Although as shown in
      this study and in previous studies, gamma c is a functional component of IL-4R in
      lymphoid cells, it does not appear to be associated with IL-4R on RCC cells. Even
      in the absence of common gamma chain IL-4 and IL-13 were able to up-regulate
      intracellular adhesion molecule-1 antigen on RCC cells. These data suggest that
      the interaction of IL-13 with IL-4R does not involve gamma c and IL-13R itself
      may be a novel subunit of the IL-4R.

PMID- 7721787
TI  - Cloning and expression of the beta-N-acetylglucosaminidase gene from
      Streptococcus pneumoniae. Generation of truncated enzymes with modified aglycon
      specificity.
AB  - The gene encoding a beta-N-acetylglucosaminidase from Streptococcus pneumoniae
      has been obtained by screening an expression library for beta-N
      acetylglucosaminidase activity. Clones of different nucleotide sizes each having
      arylglycoside activity were obtained, and DNA sequencing revealed a gene of 3933
      base pairs possessing typical bacterial transcription initiation and termination
      sequences and terminating in an ochre stop codon. Computer analysis of the
      translated protein of 1311 amino acids (144,210 Da) identified a tandem repeat
      within which lies a sequence homologous with six other hexosaminidase gene
      products from a wide variety of species ranging from bacteria to humans. Also
      found were an amino-terminal putative secretion signal peptide and a carboxyl
      terminal cell sorting/anchorage motif typically found in over 20 other Gram
      positive surface proteins. The expression of an almost complete DNA clone in
      Escherichia coli produced a functional and authentic beta-N-acetylglucosaminidase
      with aglycon specificity identical to the wild-type enzyme. However, enzymes
      produced from truncated DNA clones show more restricted aglycon specificity and
      are unable to hydrolyze terminal beta 1-2GlcNAc residues from N-glycans
      containing a bisecting N-acetylglucosamine. The availability of these clones
      allows structural analyses to be made of catalytic and oligosaccharide
      recognition protein domains that enhance functional activity.

PMID- 7721788
TI  - Oligomerization of a trans-Golgi/trans-Golgi network retained protein occurs in
      the Golgi complex and may be part of its retention.
AB  - The mouse hepatitis virus M protein is a triple spanning membrane glycoprotein
      that, when expressed independently, localizes to trans-Golgi as well as to the
      trans-Golgi network (TGN). Passage of this protein from the endoplasmic reticulum
      through the intermediate compartment to the late Golgi and TGN can be
      conveniently followed by analyzing its O-linked sugars. Using pulse-chase
      analyses we studied the oligomerization of the M protein in sucrose gradients.
      The Golgi and TGN forms migrated as large heterogeneous complexes, whereas the
      endoplasmic reticulum and intermediate compartment forms of the protein appeared
      to migrate as monomer. Moreover, a mutant of the M protein lacking the 22 COOH
      terminal amino acids, that is transported to the plasma membrane, gave rise to
      similar complexes, albeit smaller in size, that persisted at the plasma membrane.
      We propose that the trans-Golgi/TGN retention of the MHV-M protein is governed by
      two mechanisms: oligomerization possibly mediated by the transmembrane domains
      and binding of its cytoplasmic tail to cellular factors in trans Golgi/TGN.

PMID- 7721789
TI  - cDNA cloning and characterization of lamina-associated polypeptide 1C (LAP1C), an
      integral protein of the inner nuclear membrane.
AB  - Lamina-associated polypeptides 1A-1C (LAPs1A-1C) are related integral membrane
      proteins of the inner nuclear membrane that bind to both A- and B-type lamins and
      have a putative role in the membrane attachment and assembly of the nuclear
      lamina. In this study, we have cloned a cDNA encoding LAP1C. The DNA sequence
      predicts a 506-amino acid protein of largely hydrophilic character with a single
      membrane-spanning region between residues 311-333. Mapping of the epitope
      recognized by the anti-LAP1 monoclonal antibody RL13 indicates that the
      hydrophilic domain containing residues 1-310 is exposed to the nucleoplasm and
      thus that LAP1C is a type II integral membrane protein. A second class of LAP1
      cDNAs was isolated that contains two protein-coding nucleotide insertions in the
      LAP1C sequence. These probably encode parts of LAPs1A and/or -1B, suggesting that
      LAP1 isotypes arise from alternative splicing. Immunoblot analysis of mouse P19
      teratocarcinoma cells and the P19MES-differentiated derivative of the latter
      suggest that LAP1 isotypes are differentially expressed during development,
      similar to members of the nuclear lamin family. Since the different LAP1 isotypes
      appear to bind lamins with different affinities, these changes in expression
      could be important for developmentally regulated alterations in nuclear
      structure.

PMID- 7721790
TI  - Mutually exclusive interactions between factors binding to adjacent Sp1 and AT
      rich elements regulate gastrin gene transcription in insulinoma cells.
AB  - The gastrin gene is transiently expressed in fetal pancreatic islets during islet
      neogenesis but then switched off after birth when islet cells become fully
      differentiated. Previous studies identified a cis-regulatory sequence between 
      109 and -75 in the human gastrin promoter which binds islet cell-specific
      activators and a nonspecific repressor and thus may act as a molecular switch.
      The present study identified another cis-regulatory sequence (
      163ACACTAAATGAAAGGGCGGGGCAG-140) which bound two islet nuclear proteins in a
      mutually exclusive manner, as defined by gel shift competition, methylation
      interference, and DNase I foot-printing assays. The general transactivator Sp1
      recognized the downstream GGGCGGGG sequence, but Sp1 binding was prevented when
      another islet factor bound to the adjacent AT-rich sequence (CTAAATGA). This
      gastrin AT-rich element is nearly identical to the binding site (ATAAATGA) for
      the islet-specific transcription factor beta TF-1. However, the gastrin AT
      binding factor appeared to differ from beta TF-1 in its gel mobility shift
      pattern. Transfections of rat insulinoma cells revealed that mutations which
      blocked binding to the AT-rich element but allowed Sp1 binding up-regulated
      transcriptional activity. These results suggest that the gastrin AT-binding
      factor blocks transactivation by Sp1 and may have a role in the repression of
      gastrin transcription seen at the end of islet differentiation.

PMID- 7721791
TI  - The retinoblastoma susceptibility gene product represses transcription when
      directly bound to the promoter.
AB  - Rb represses E2F-mediated transcription in part by blocking the trans-activation
      domain of E2F. In addition, Rb can convert an E2F binding site from a positive to
      a negative element. To examine the effect of a Rb-DNA-bound complex on
      transcription, full-length Rb was fused to the DNA binding domain of GAL4. Here,
      we report that GAL4-Rb can repress transcription mediated by either Sp1, AP-1, or
      p53, dependent upon the presence of both the GAL4 DNA binding domain and GAL4
      binding sites. Moreover, GAL4-Rb inhibited the activity of the herpes simplex
      virus tk promoter from GAL4 binding sites located at a distance from the
      promoter. In contrast, GAL4-Rb was unable to repress basal transcription.
      Cotransfection of specific cyclins and cyclin-dependent kinases or SV40 T-antigen
      abolished the repressive activity of GAL4-Rb. The domains of Rb involved in
      mediating the repression of transcription were mapped to regions that are
      overlapping, but not identical, to those required for the interaction with E2F.
      We propose that Rb can function as a general repressor of transcription when
      bound to the promoter region.

PMID- 7721792
TI  - Molecular cloning and expression of two types of rabbit beta-galactoside alpha
      1,2-fucosyltransferase.
AB  - Two DNA clones encoding rabbit beta-galactoside alpha 1,2-fucosyltransferase (RFT
      I and RFT-II) have been isolated from a rabbit genomic DNA library. The DNA
      sequences revealed open reading frames coding for 373 (RFT-I) and 354 (RFT-II)
      amino acids, respectively. The deduced amino acid sequences of RFT-I and RFT-II
      showed 56% identity with each other, and that of RFT-I showed 80% identity with
      that of human H blood type alpha 1,2-fucosyltransferase. Northern blot analysis
      of embryo and adult rabbit tissues revealed that the RFT-I gene was expressed in
      adult brain, and that the RFT-II gene was expressed in salivary and lactating
      mammary glands. The identities of these enzymes were confirmed by constructing
      recombinant fucosyltransferases in which the N-terminal part including the
      cytoplasmic tail and signal anchor domain was replaced with the immunoglobulin
      signal peptide sequence. RFT-I expressed in COS-7 cells exhibited similar
      transferase activity to that of human H blood type alpha 1,2-fucosyltransferase.
      RFT-II expressed in COS-7 cells showed higher affinity for type 1 (Gal beta
      1,3GlcNAc) and type 3 (Gal beta 1,3GalNAc) acceptors than type 2 (Gal beta
      1,4GlcNAc) ones, which suggested that RFT-II was a putative secretor-type alpha
      1,2-fucosyltransferase.

PMID- 7721793
TI  - Cloning of the promoter-regulatory region of the murine growth hormone receptor
      gene. Identification of a developmentally regulated enhancer element.
AB  - The growth hormone (GH) receptor is essential for the actions of GH on postnatal
      growth and metabolism. To identify DNA sequences involved in the regulation of
      transcription of the murine GH receptor gene, a 17-kilobase genomic clone
      containing the 5'-flanking region, exon 1, and part of intron 1 of the murine GH
      receptor gene was isolated. Utilizing primer extension and ribonuclease
      protection assays, two major transcription start sites were identified in RNA
      from liver of male, female, and pregnant mice. Transient transfection studies
      using a reporter gene demonstrated promoter activity in a variety of eukaryotic
      cells. Deletional analysis and DNA-protein binding assays led to the
      identification of a 30-base pair enhancer element located about 3.4 kilobases
      upstream of the transcription start sites. Computer analysis of the nucleotide
      sequence of the enhancer element did not reveal any potential DNA binding motifs
      for known transcription factors, and this DNA element failed to exhibit binding
      activity for some common transcription factors. Analysis of both functional
      activity and DNA-protein binding activity of this enhancer element in adult and
      fetal hepatocytes suggests that this DNA element may play a role in the
      developmental expression of the GH receptor gene.

PMID- 7721794
TI  - Characterization of the regulatory domain of gizzard calponin. Interactions of
      the 145-163 region with F-actin, calcium-binding proteins, and tropomyosin.
AB  - Earlier, we proposed that the interaction of gizzard calponin with F-actin,
      promoting the inhibition of the actomyosin ATPase activity, involves the NH2
      terminal portion of the calponin segment Ala145-Tyr182 (Mezgueldi, M., Fattoum,
      A., Derancourt, J., and Kassab, R. (1992) J. Biol. Chem. 267, 15943-15951). In
      this work, we have directly probed this region for actin binding sites using five
      peptide analogs covering different stretches of the sequence Thr133-Ile163. Co
      sedimentation with F-actin, actomyosin ATPase measurements, and zero-length cross
      linking reactions demonstrated that the 19-residue sequence Ala145-Ile163 is
      essential for actin interaction and ATPase inhibition. Furthermore, each peptide
      was tested for binding to the Ca(2+)-dependent proteins, caltropin and
      calmodulin, in both an actomyosin ATPase assay and an affinity chromatographic
      assay. The results revealed the 11-residue segment Gln153-Ile163, representing
      the COOH-terminal moiety of the F-actin binding sequence, as a crucial region for
      the high affinity binding of these regulatory proteins with concomitant removal
      of the ATPase inhibition. The 153-163 stretch contained also interactive sites
      for tropomyosin as assessed by affinity chromatography and spectrofluorometry.
      Collectively, the data support our initial results and highlight the ability of
      the multifunctional 145-163 region to serve as a potent regulatory domain of the
      smooth muscle calponin.

PMID- 7721795
TI  - Decorin-type I collagen interaction. Presence of separate core protein-binding
      domains.
AB  - Interactions between the core protein of the small dermatan sulfate proteoglycan
      decorin and type I collagen have been considered to influence the kinetics of
      collagen fibrillogenesis and the diameter of and the distance between the
      fibrils. A variety of recombinant core protein fragments were expressed in
      Escherichia coli, extracted from inclusion bodies, and renatured in the presence
      of bovine serum albumin, which was essential for obtaining functional activity. A
      recombinant protein lacking the first 14 amino acids of the mature core protein
      (P15-329) interacted with reconstituted type I collagen fibrils and inhibited
      collagen fibrillogenesis almost as efficiently as intact decorin purified from
      fibroblast secretions under non-denaturing conditions. Peptides comprising amino
      acids 15-183 (P15-183) and 185-329 (P185-329) were able to compete for the
      binding of wild-type decorin, with P15-183 being more active than P185-329.
      Several other peptides were much less effective. Binding studies using
      radioactively labeled peptides P15-183 and P185-329 gave direct evidence for the
      independent binding of both peptides. Peptides 15-183 and 15-125 had the
      capability of inhibiting collagen fibrillogenesis, whereas peptide 185-329 was
      inactive. These data suggest (i) that there are at least two separate binding
      domains for the interaction between decorin core protein and type I collagen and
      (ii) that binding is not necessarily correlated with an alteration of collagen
      fibrillogenesis.

PMID- 7721796
TI  - Developmentally regulated expression of a novel 59-kDa product of the major
      surface protease (Msp or gp63) gene family of Leishmania chagasi.
AB  - All species of Leishmania express a major surface protease (Msp or gp63) that
      facilitates the interactions of the parasite with its environment at several
      steps in its life cycle. The msp gene family in Leishmania chagasi contains three
      classes of genes whose mRNAs are differentially expressed during parasite growth.
      Logarithmic phase (low infectivity) promastigotes express only 63-kDa versions of
      Msp, whereas stationary phase (high infectivity) promastigotes express both 63-
      and 59-kDa Msps. The different migrations of the 59- and 63-kDa proteins on
      acrylamide gels are not due to differences in N-linked glycosylation or the
      membrane anchor. Plasmid transfections of Leishmania demonstrate that mspS2 of
      the stationary gene class encodes a 59-kDa protein. Expression of the 59-kDa
      protein in stationary phase promastigotes ceases after about 12 weeks of in vitro
      cultivation when the parasites become attenuated. Attenuated parasites can be
      stimulated to re-express the 59-kDa Msp by passage through mice followed by
      several in vitro passages of recovered promastigotes. Amastigotes express yet
      another subset of Msp proteins. Thus, the 59-kDa product of mspS2 is expressed
      only in stationary phase promastigotes and only after recent exposure to
      environmental changes encountered in the mammalian host cell.

PMID- 7721797
TI  - Gel shift and UV cross-linking analysis of Tetrahymena telomerase.
AB  - Telomerase is an unusual ribonucleoprotein that synthesizes new telomeres onto
      chromosome ends. The enzyme has been most extensively characterized in ciliates,
      where the RNA component has been cloned from several species, and its elongation
      properties have been characterized in detail. To understand the substrate
      specificity and protein composition of telomerase, we have used gel shift and UV
      cross-linking to characterize the enzyme from the ciliate Tetrahymena
      thermophila. In a mobility shift assay, a complex was identified that contained
      telomerase RNA, co-purified with telomerase activity, and was sensitive to
      nuclease treatment. The mobility shift complexes specifically formed using
      several different single-stranded, telomeric sequences but not non-telomeric
      primers. These results suggest that the specificity of telomerase for G-rich
      primer sequences occurs at least in part at the level of primer binding. UV cross
      linking analysis identified a 100-kDa cross-linked protein that may be a
      telomerase component.

PMID- 7721798
TI  - Agonist regulation of alpha 1B-adrenergic receptor subcellular distribution and
      function.
AB  - We have monitored agonist-induced alpha 1B-adrenergic receptor (alpha 1BAR)
      redistribution by immunocytochemical procedures in concert with functional
      measurements of agonist-elicited [3H]inositol phosphate (InsP) production in
      human embryonal kidney 293 cells stably expressing alpha 1BAR cDNA (HEK293/alpha
      1B). Anti-peptide antibodies directed against the carboxyl-terminal decapeptide
      of the alpha 1BAR were prepared and shown to react specifically with alpha 1BAR
      on immunoblots and in situ in HEK293/alpha 1B transfectants. Treatment of
      HEK293/alpha 1B cells with norepinephrine (10 microM) results in a rapid (5-15
      min) and striking internalization of cell surface receptor as visualized by
      confocal immunofluorescence microscopy. Receptor redistribution is sustained in
      the presence of agonist, rapidly reversed upon agonist removal, and prevented by
      the alpha 1 antagonist prazosin. Receptor internalizes to endosomes, as shown by
      colocalization with transferrin receptor, an endosomal marker. Activation of
      protein kinase C (PKC) with phorbol 12-myristate 13-acetate (50 nM) causes
      receptor endocytosis similar to agonist; agonist-induced internalization is
      blocked by the PKC inhibitor staurosporine (0.5 microM). In parallel experiments,
      agonist-induced [3H]InsP production is abolished by phorbol 12-myristate 13
      acetate but potentiated by staurosporine. Inhibition of receptor internalization
      with hypertonic sucrose attenuates agonist-induced [3H]InsP formation; this
      effect is reversed by concomitant inhibition of PKC with staurosporine. These
      results suggest that PKC-dependent phosphorylation occurring as a consequence of
      alpha 1AR stimulation induces receptor desensitization and internalization.
      Internalized receptor is reactivated and continuously recycled to the cell
      surface during agonist exposure.

PMID- 7721799
TI  - Differences in the mechanism of stimulation of T7 DNA polymerase by two binding
      modes of Escherichia coli single-stranded DNA-binding protein.
AB  - Escherichia coli single-stranded DNA-binding protein (Eco SSB) has been shown
      previously to display several DNA binding modes depending on the ionic
      conditions. To determine what effect these various binding modes have on DNA
      replication, we have studied DNA synthesis by the T7 DNA polymerase under ionic
      conditions where Eco SSB interacts with either 72 or 91 nucleotides of M13 DNA.
      These forms presumably correspond to the previously described (SSB)56 and (SSB)65
      (Lohman and Ferrari, 1994) that were determined using the binding of SSB to
      homopolymers. Here we report the stimulation induced by (SSB)91 to be 4-fold
      greater than that produced by (SSB)72 under conditions where the template is in
      large excess. Surprisingly, when the polymerase level is raised so that it is in
      molecular excess, (SSB)91 no longer stimulates synthesis while (SSB)72 affords a
      4-fold stimulation, which is the same level of stimulation as when the template
      was in excess. Both SSB forms increase the rate of DNA synthesis and were found
      to stimulate synthesis by relieving template secondary structures. However,
      (SSB)72 specifically increases strand displacement synthesis, while (SSB)91
      stimulates synthesis by increasing the affinity of the polymerase for the
      template.

PMID- 7721800
TI  - Molecular characterization of pyocin S3, a novel S-type pyocin from Pseudomonas
      aeruginosa.
AB  - The genetic determinant for the soluble pyocin S3 was isolated from a genomic
      library constructed in the plasmid pGV1122, of Pseudomonas aeruginosa strain P12
      isolated from a cystic fibrosis patient. The nucleotide sequence of a 3270-base
      pair DNA fragment was determined, and the two structural genes, pyoS3A and
      pyoS3I, and the 3'- and 5'-flanking regions were localized. Transcription
      (Northern blot) analysis showed that the two genes were co-transcribed. The genes
      pyoS3A and pyoS3I code for polypeptides of 767 and 154 amino acids, respectively,
      with calculated molecular weights of 81,385 and 17,047. Pyocin S3 was produced in
      Escherichia coli from a plasmid and purified as a complex of two components (S3A
      and S3I) corresponding to the pyoS3A and pyoS3I gene products, respectively. The
      S3A component, like pyocin S3, had a killing effect involving DNase activity and
      was inhibited by the S3I protein. Comparisons of the predicted amino acid
      sequence of the two components of pyocin S3 to those of pyocins S1, S2, and AP41
      indicate that pyocin S3 is a new type of S-type pyocin.

PMID- 7721801
TI  - Ubiquitin is conjugated to the cytoskeletal protein alpha-spectrin in mature
      erythrocytes.
AB  - Ubiquitination of red blood cell (RBC) proteins was investigated by encapsulation
      of 125I-ubiquitin into human erythrocytes using a procedure of hypotonic
      dialysis, isotonic resealing, and reannealing. Incubation (37 degrees C, up to 2
      h) of 125I-ubiquitin-loaded cells resulted in the recovery of 125I-ubiquitin with
      the cytosolic proteins (9.22 +/- 0.4 micrograms/ml RBC) and conjugated to
      membrane proteins (2.18 +/- 0.05 micrograms/ml RBC). This conjugation was time
      dependent, and the predominant membrane protein band that became labeled showed
      an apparent molecular mass of 240 kDa on SDS-polyacrylamide gel electrophoresis
      (PAGE). Western blotting experiments with three different anti-ubiquitin
      antibodies revealed that this protein is also ubiquitinated in vivo. Cell-free
      experiments have shown that fraction II (a DEAE-bound protein fraction eluted by
      0.5 M KCl) prepared from both mature erythrocytes and reticulocytes is able to
      conjugate ubiquitin to this protein. Ubiquitin conjugation was ATP-dependent (Km
      0.09 mM), time-dependent, and fraction II-dependent (8 +/- 0.5 pmol of 125I
      ubiquitin/h/mg of fraction II). Isolation of the major RBC membrane protein that
      is ubiquitinated was obtained by using biotinylated ubiquitin. Membrane proteins,
      once ubiquitinated with this derivative, were extracted and purified by affinity
      chromatography on immobilized avidin. The major components retained by the column
      were two peptides of molecular masses 220 and 240 kDa. Both proteins are
      recognized by a monoclonal anti-spectrin antibody, but only the 240-kDa component
      is detected by streptavidin peroxidase conjugate. That indeed the ubiquitinated
      membrane protein of 240-kDa is alpha-spectrin was confirmed by immunoaffinity
      chromatography using 125I-ubiquitin and a monoclonal anti-spectrin antibody.
      Antigen-antibody complexes were purified by protein A chromatography and analyzed
      by SDS-PAGE and autoradiography. Again two bands of 240 and 220 kDa were eluted
      (alpha- and beta-spectrin), but only one band corresponding to the
      electrophoretic mobility of alpha-spectrin was detected by autoradiography. Thus,
      alpha-spectrin is a substrate for the ATP-dependent ubiquitination system,
      suggesting that the cytoskeleton is covalently modified by ubiquitination both in
      reticulocytes and mature RBC.

PMID- 7721802
TI  - The relationship between eukaryotic translation and mRNA stability. A short
      upstream open reading frame strongly inhibits translational initiation and
      greatly accelerates mRNA degradation in the yeast Saccharomyces cerevisiae.
AB  - A new strategy was developed to study the relationship between the translation
      and degradation of a specific mRNA in the yeast Saccharomyces cerevisiae. A
      series of 5'-untranslated regions (UTR) was combined with the cat gene from the
      bacterial transposon Tn9, allowing us to test the influence of upstream open
      reading frames (uORFs) on translation and mRNA stability. The 5'-UTR sequences
      were designed so that the minimum possible sequence alteration, a single
      nucleotide substitution, could be used to create a 7-codon ORF upstream of the
      cat gene. The uORF was translated efficiently, but at the same time inhibited
      translation of the cat ORF and destabilized the cat mRNA. Investigations of
      various derivatives of the 5'-UTR indicated that cat translation was primarily
      attributable to leaky scanning of ribosomes past the uORF rather than to
      reinitiation. Therefore, these data directly demonstrate destabilization of a
      specific mRNA linked to changes in translational initiation on the same
      transcript. In contrast to the previously proposed nonsense-mediated mRNA decay
      pathway, destabilization was not triggered by premature translational termination
      in the main ORF and was not discernibly dependent upon a reinitiation-driven
      mechanism. This suggests the existence of an as yet not described pathway of
      translation-linked mRNA degradation.

PMID- 7721803
TI  - C-terminal truncation of the neurokinin-2 receptor causes enhanced and sustained
      agonist-induced signaling. Role of receptor phosphorylation in signal
      attenuation.
AB  - The G protein-linked receptor for neurokinin A (NKA) couples to stimulation of
      phospholipase C and, in some cells, adenylyl cyclase. We have examined the
      function of the C-terminal cytoplasmic domain in receptor signaling and
      desensitization. We constructed C-terminal deletion mutants of the human NK-2
      receptor (epitope tagged) to remove potential Ser/Thr phosphorylation sites, and
      expressed them in both mammalian and insect cells. When activated, truncated
      receptors mediate stronger and more prolonged phosphoinositide hydrolysis than
      wild-type receptor; however, the amplitude and kinetics of the NKA-induced rise
      in cytosolic Ca2+ remain unaltered. Protein kinase C (PKC)-activating phorbol
      ester abolishes wild-type receptor signaling but not mutant receptor signaling.
      Mutant receptors also mediate enhanced and prolonged cAMP generation, at least in
      part via PKC activation. When expressed in COS cells or Sf9 insect cells, the
      wild-type receptor is phosphorylated; receptor phosphorylation increases after
      addition of either NKA or phorbol ester. In contrast, mutant receptors are not
      phosphorylated by either treatment. Our results suggest that C-terminal Ser/Thr
      phosphorylation sites in the NK-2 receptor have a critical role in both
      homologous and heterologous desensitization. Removal of these phosphorylation
      sites results in a receptor that mediates sustained activation of signaling
      pathways and is insensitive to inhibition by PKC.

PMID- 7721804
TI  - Mitochondrial carnitine palmitoyltransferase I isoform switching in the
      developing rat heart.
AB  - The expression pattern of mitochondrial carnitine palmitoyltransferase (CPT)
      enzymes was examined in the developing rat heart. Whereas the specific activity
      of CPT II increased approximately 3-fold during the first month of life, the
      profile for CPT I, which is composed of both liver (L) and muscle (M) isoforms,
      was more complex. Exposure of mitochondria to [3H]etomoxir (a covalent ligand for
      CPT I), followed by fluorographic analysis of the membrane proteins, established
      that while in the adult heart L-CPT I represents a very minor constituent, its
      contribution is much greater in the newborn animal. Use of the related inhibitor,
      2-[6-(2,4-dinitrophenoxy)hexyl]oxirane-2-carboxylic acid (specific for L-CPT I),
      allowed the activities of the two CPT I variants to be quantified separately. The
      results showed that in the neonatal heart, L-CPT I contributes approximately 25%
      to total CPT I activity (in Vmax terms), the value falling during growth of the
      pups (with concomitant increasing expression of the M isoform) to its adult level
      of 2-3%. Because the myocardial carnitine content is very low at birth and rises
      dramatically over the next several weeks, it can be estimated that L-CPT I (Km
      for carnitine of only 30 microM compared with a value of 500 microM for M-CPT I)
      is responsible for some 60% of total cardiac fatty acid oxidation in the newborn
      rat; the value falls to approximately 4% in adult animals. Should these findings
      have a parallel in humans, they could have important implications for
      understanding the pathophysiological consequences of inherited L-CPT I deficiency
      syndromes.

PMID- 7721805
TI  - Tumor necrosis factor alpha facilitates nuclear actions of retinoic acid to
      regulate expression of the alkaline phosphatase gene in preosteoblasts.
AB  - This study examines the molecular mechanisms of interaction between tumor
      necrosis factor alpha (TNF alpha) and retinoic acid on the expression of the
      alkaline phosphatase gene by rat clonal preosteoblastic cells. In this cell line,
      alkaline phosphatase mRNA was not constitutively expressed but was progressively
      induced by treatment with 1 microM retinoic acid, detectable by 6 h. Combining
      retinoic acid with 0.6 nM TNF alpha resulted in alkaline phosphatase mRNA
      appearing by 2 h, as well as enhanced expression above that observed with
      retinoic acid alone at 6, 12, and 24 h. Nuclear run-on analysis showed
      constitutive transcription of the alkaline phosphatase gene in control and TNF
      alpha-treated cells. At 4 h, retinoic acid, alone or combined with TNF alpha,
      increased alkaline phosphatase gene transcriptional rate by 2-fold. However, at
      24 h, while no retinoic acid effect was retained, retinoic acid plus TNF alpha
      resulted in a 5-fold increase in alkaline phosphatase transcriptional rate.
      Examination of the distribution of nuclear alkaline phosphatase mRNA demonstrated
      that pre-spliced precursor mRNA was localized to the nuclear matrix in control
      and all treatment groups. Retinoic acid caused a time-dependent accumulation of
      mature, spliced alkaline phosphatase mRNA located in the non-matrix and
      cytoplasmic fractions, implying a post-transcriptional action of retinoic acid in
      nuclear processing and nucleocytoplasmic transport. Adding TNF alpha with
      retinoic acid greatly enhanced this effect, which was observed after 4 h, prior
      to any detectable interaction between TNF alpha and retinoic acid on gene
      transcription. In sharp contrast, only a negligible amount of nuclear processing
      occurred in control and TNF alpha-treated cells. This study reveals distinct
      interactions between TNF alpha and retinoic acid at post-transcriptional as well
      as transcriptional levels to regulate expression of the alkaline phosphatase gene
      in preosteoblasts.

PMID- 7721806
TI  - The human 180-kDa receptor for secretory phospholipases A2. Molecular cloning,
      identification of a secreted soluble form, expression, and chromosomal
      localization.
AB  - Secretory phospholipases A2 (sPLA2) are structurally related enzymes found in
      mammals as well as in insect and snake venoms. They have been associated with
      several physiological, pathological, and toxic processes. Some of these effects
      are apparently linked to the existence of specific receptors for both venom and
      mammalian sPLA2s. We report here the molecular cloning and expression of one of
      these sPLA2 receptors from human kidney. Two transcripts were detected. One
      encodes for a transmembrane form of the sPLA2 receptor and the other one is an
      alternatively processed transcript, caused by polyadenylation occurring at a site
      within an intron in the C terminus part of the transcriptional unit. This
      transcript encodes for a shortened secreted soluble sPLA2 receptor lacking the
      coding region for the transmembrane segment. Quantitative polymerase chain
      reaction experiments indicate a 1.6:1 ratio between the levels of transcripts
      encoding for the membrane-bound and soluble forms of the receptor, respectively.
      Soluble and membrane-bound human sPLA2 receptors both bind sPLA2 with high
      affinities. However, the binding properties of the human receptors are different
      from those obtained with the rabbit membrane-bound sPLA2 receptor. The 180-kDa
      human sPLA2 receptor gene has been mapped in the q23-q24 bands of chromosome 2.

PMID- 7721807
TI  - Differences in glucose transporter gene expression between rat pancreatic alpha-
      and beta-cells are correlated to differences in glucose transport but not in
      glucose utilization.
AB  - Glucose exerts inverse effects upon the secretory function of islet alpha- and
      beta-cells, suppressing glucagon release and increasing insulin release. This
      diverse action may result from differences in glucose transport and metabolism
      between the two cell types. The present study compares glucose transport in rat
      alpha- and beta-cells. beta-Cells transcribed GLUT2 and, to a lesser extent, GLUT
      1; alpha-cells contained GLUT1 but no GLUT2 mRNA. No other GLUT-like sequences
      were found among cDNAs from alpha- or beta-cells. Both cell types expressed 43
      kDa GLUT1 protein which was enhanced by culture. The 62-kDa beta-cell GLUT2
      protein was converted to a 58-kDa protein after trypsin treatment of the cells
      without detectable consequences upon glucose transport kinetics. In beta-cells,
      the rates of glucose transport were 10-fold higher than in alpha-cells. In both
      cell types, glucose uptake exceeded the rates of glucose utilization by a factor
      of 10 or more. Glycolytic flux, measured as D-[5(3)H]glucose utilization, was
      comparable in alpha- and beta-cells between 1 and 10 mmol/liter substrate. In
      conclusion, differences in glucose transporter gene expression between alpha- and
      beta-cells can be correlated with differences in glucose transport kinetics but
      not with different glucose utilization rates.

PMID- 7721808
TI  - Prostaglandin F2 alpha stimulates formation of p21ras-GTP complex and mitogen
      activated protein kinase in NIH-3T3 cells via Gq-protein-coupled pathway.
AB  - Prostaglandin (PG) F2 alpha activated mitogen-activated protein (MAP) kinase and
      MAP kinase kinase in NIH-3T3 cells by a mechanism that was completely inhibited
      by protein kinase inhibitors, staurosporine (20 nM) or H-7 (20 microM), but was
      insensitive to pretreatment with islet-activating protein (100 ng/ml; 24 h) or 12
      O-tetradecanoylphorbol 13-acetate (2.5 microM; 24 h). PGF2 alpha stimulation also
      led to a significant increase in Ras.GTP complex. Transfection of a cDNA encoding
      a constitutively active mutant of Gq alpha-subunit (Q209L) mimicked PGF2 alpha
      induced MAP kinase activation, increase in Ras.GTP complex, and DNA synthesis in
      these cells, suggesting that activation of Gq mediates the PGF2 alpha-activation
      of Ras-MAP kinase pathway and mitogenesis in NIH-3T3 cells. These data provide a
      new insight into regulatory mechanisms of Ras-MAP kinase pathway through
      heterotrimeric G-protein-mediated pathways.

PMID- 7721809
TI  - Structure-function relationship of yeast S-II in terms of stimulation of RNA
      polymerase II, arrest relief, and suppression of 6-azauracil sensitivity.
AB  - The yeast S-II null mutant is viable, but the mutation induces sensitivity to 6
      azauracil. To examine whether the region needed for stimulation of RNA polymerase
      II and that for suppression of 6-azauracil sensitivity in the S-II molecule could
      be separated, we constructed various deletion mutants of S-II and expressed them
      in the null mutant using the GAL1 promoter to see if the mutant proteins
      suppressed 6-azauracil sensitivity. We also expressed these constructs in
      Escherichia coli, purified the mutant proteins to homogeneity, and examined if
      they stimulated RNA polymerase II. We found that a mutant protein lacking the
      first 147 amino acid residues suppressed 6-azauracil sensitivity but that removal
      of 2 additional residues completely abolished the suppression. A mutant protein
      lacking the first 141 residues had activity to stimulate RNA polymerase II,
      whereas removal of 10 additional residues completely abolished this activity. We
      also examined arrest-relief activity of these mutant proteins and found that
      there is a good correlation between RNA polymerase II-stimulating activity and
      arrest-relief activity. Therefore, at least the last 168 residues of S-II are
      sufficient for expressing these three activities.

PMID- 7721810
TI  - Growth factor-induced phosphorylation and activation of aortic smooth muscle
      Na+/Ca2+ exchanger.
AB  - Although the Na+/Ca2+ exchanger is one of the major Ca2+ extrusion systems in
      excitable tissues, little is known about its regulation via protein
      phosphorylation. We now present evidence that the Na+/Ca2+ exchanger is
      phosphorylated in quiescent and growth factor-stimulated cultured aortic smooth
      muscle cells. The Na+/Ca2+ exchanger was isolated from 32P-labeled cells by
      immunoprecipitation with a specific polyclonal antibody. Phosphorylation of the
      exchanger was increased by up to 1.7-fold in response to platelet-derived growth
      factor-BB (PDGF-BB), alpha-thrombin, or phorbol 12-myristate 13-acetate (PMA).
      However, angiotensin II did not enhance the phosphorylation significantly. The
      extent of phosphorylation appeared to correlate with the growth factor-induced
      increase in cell 1,2-diacylglycerol. At least four phosphopeptides (P1 to P4)
      were detected by tryptic phosphopeptide map analysis of the phosphorylated
      exchanger, suggesting that phosphorylation occurred at multiple sites. PDGF-BB
      and PMA increased phosphorylation of the same phosphopeptides (in particular P1).
      Phosphorylated amino acids were exclusively serine residues in both quiescent and
      stimulated cells. We found that growth factors enhanced Na+/Ca2+ exchange
      activity and that there was a good correlation between the growth factor-induced
      stimulations of phosphorylation and exchange activity. PDGF-BB-induced activation
      of the exchanger was abolished by prior long treatment of cells with PMA. These
      results suggest that the Na+/Ca2+ exchanger is activated by protein kinase C
      dependent phosphorylation in response to growth factors in vascular smooth muscle
      cells.

PMID- 7721811
TI  - Cell-specific function of cis-acting elements in the regulation of human alcohol
      dehydrogenase 5 gene expression and effect of the 5'-nontranslated region.
AB  - The human alcohol dehydrogenase 5 gene (ADH5) differs from all other human
      alcohol dehydrogenase genes in its ubiquitous expression, although there are
      tissue-specific differences in the level of expression. To understand the
      expression of ADH5, we characterized the structure and function of its 5' region
      by DNase I foot-printing and transient transfection assays. The region from base
      pair (bp) -34 to +61, flanking the major transcription start site, had strong
      promoter activity in three different cell lines: HeLa, H4IIE-C3, and CV-1, and
      could explain the ubiquitous expression. Two Sp1 sites within that region are
      footprinted by nuclear extracts from all tissues and cells tested. There are
      sites further upstream that show cell- and tissue-specific differences in both
      their patterns of occupancy and their effects on promoter activity. The region
      between bp -34 and -64 strongly increases promoter activity in H4IIE-C3 cells,
      weakly activates in CV-1 cells, but has no effect in HeLa cells. The region
      between bp -127 and -163 is a positive element in both HeLa cells and CV-1 cells,
      but is a negative regulatory element in H4IIE-C3 cells. These differences in part
      explain the levels of expression of ADH5 in various tissues. Two regions (bp -64
      to -127 and bp -163 to -365) contain negative regulatory elements that reduce
      promoter activity in all three cells. The 5'-nontranslated region of ADH5
      contains two upstream ATGs. Insertion of 12 bp within the putative coding region
      of these upstream ATGs led to a 1.6-2.3-fold increase in activity. This suggests
      that the 5'-nontranslated region has regulatory significance.

PMID- 7721812
TI  - Glycoconjugate receptors for P-fimbriated Escherichia coli in the mouse. An
      animal model of urinary tract infection.
AB  - Glycosphingolipids were isolated from kidneys, urethers, and bladders (including
      urethrae) of C3H/HeN mice. Binding was studied of a clinical isolate and
      recombinant strains of uropathogenic P-fimbriated Escherichia coli to these
      glycolipids. A series of receptor-active glycolipids with Gal alpha 4Gal in
      common, previously shown to be recognized by these bacteria, was identified by
      use of specific monoclonal antibodies, fast-atom bombardment and electron-impact
      mass spectrometry, and proton nuclear magnetic resonance spectroscopy:
      galabiosylceramide (Gal alpha 4Gal beta Cer), globotriaosylceramide (Gal alpha
      4Gal beta 4Glc beta Cer), globoside (GalNAc beta 3Gal alpha 4Gal beta 4Glc beta
      Cer), the Forssman glycolipid (GalNAc alpha 3GalNAc beta 3Gal alpha 4Gal beta
      4Glc beta Cer), Gal beta 4GlcNAc beta 6(Gal beta 3)GalNAc beta 3Gal alpha 4Gal
      beta 4Glc beta Cer, and Gal beta 4(Fuc alpha 3)GlcNAc beta 6(Gal beta 3)GalNAc
      beta 3Gal alpha 4Gal beta 4Glc beta Cer. The binding pattern for mouse kidney
      glycolipids differed from that for kidney glycolipids of man and monkey. In
      particular, the dominant 8-sugar glycolipid in the mouse was not detected in the
      primates. A second difference was found in the binding of E. coli to kidney
      glycoproteins on blots after electrophoresis; the mouse showed distinct receptor
      active bands while human and monkey did not. These differences may be of
      relevance when using the mouse as a model for clinical urinary tract infection of
      man.

PMID- 7721813
TI  - Association of triadin with the ryanodine receptor and calsequestrin in the lumen
      of the sarcoplasmic reticulum.
AB  - Triadin is a major membrane protein that is specifically localized in the
      junctional sarcoplasmic reticulum of skeletal muscle and is thought to play an
      important role in muscle excitation-contraction coupling. In order to identify
      the proteins in the skeletal muscle that interact with triadin, the cytoplasmic
      and luminal domains of triadin were expressed as glutathione S-transferase fusion
      proteins and immobilized to glutathione-Sepharose to form affinity columns. Using
      these affinity columns, we find that triadin binds specifically to the ryanodine
      receptor/Ca2+ release channel and the Ca(2+)-binding protein calsequestrin from
      CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid)-solubilized
      skeletal muscle homogenates. The luminal but not the cytoplasmic domain of
      triadin-glutathione S-transferase fusion protein binds [3H]ryanodine receptor,
      whereas neither the cytoplasmic nor the luminal portion of triadin binds [3H]PN
      200-100-labeled dihydropyridine receptor. In addition, the luminal domain of
      triadin interacts with calsequestrin in a Ca(2+)-dependent manner and is capable
      of inhibiting the reassociation of calsequestrin to the junctional face membrane.
      These results suggest that triadin is the previously unidentified transmembrane
      protein that anchors calsequestrin to the junctional region of the sarcoplasmic
      reticulum, and is involved in the functional coupling between calsequestrin and
      the ryanodine receptor/Ca2+ release channel.

PMID- 7721814
TI  - Direct involvement of the small GTP-binding protein Rho in lbc oncogene function.
AB  - The lbc oncogene is tumorigenic in nude mice, transforms NIH 3T3 fibroblasts, and
      encodes a Dbl homology domain found in several transforming gene products
      including the dbl oncogene product. While both lbc- and dbl-transformed NIH 3T3
      foci exhibited a comparable gross appearance, lbc-transformed cell morphology was
      clearly distinct from that of dbl-transformed cells. Given these differences, we
      investigated the biochemical activity and target specificity of the Lbc
      oncoprotein both in vivo and in vitro. Here we show that Lbc associates
      specifically with the GTP-binding protein Rho in vivo, but not with the Ras, Rac,
      or Cdc42Hs GTP-binding proteins, and that recombinant, affinity-purified Lbc
      specifically catalyzes the guanine-nucleotide exchange activity of Rho in vitro.
      Consistent with an in vivo role for Lbc in Rho regulation, we further demonstrate
      that micro-injected onco-lbc potently induces actin stress fiber formation in
      quiescent Swiss 3T3 fibroblasts indistinguishable from that induced by Rho.
      Finally, lbc-induced NIH 3T3 focus formation is inhibited by co-transfection with
      a rho dominant-negative mutant. These results strongly indicate that the lbc
      oncogene encodes a specific guanine nucleotide exchange factor for Rho and causes
      cellular transformation through activation of the Rho signaling pathway.

PMID- 7721815
TI  - Absence of the skeletal muscle sarcolemma chloride channel ClC-1 in myotonic
      mice.
AB  - The voltage-dependent chloride channel ClC-1 stabilizes resting membrane
      potential in skeletal muscle. Mutations in the ClC-1 gene are responsible for
      both human autosomal recessive generalized myotonia and autosomal dominant
      myotonia congenita. To understand the tissue distribution and subcellular
      localization of ClC-1 and to evaluate its role in an animal model of myotonia,
      antibodies were raised against the carboxyl terminus of this protein. Expression
      of the 130-kDa ClC-1 protein is unique to skeletal muscle, consistent with its
      mRNA tissue distribution. Immunolocalization shows prominent ClC-1 antigen in the
      sarcolemma of both type I and II muscle fibers. Sarcolemma localization is
      confirmed by Western analysis of skeletal muscle subcellular fractions. The ADR
      myotonic mouse (phenotype ADR, genotype adr/adr), in which defective ClC-1 mRNA
      has been identified, is shown here to be absent in ClC-1 protein expression,
      whereas other skeletal muscle sarcolemma protein expression appears normal.
      Immunohistochemistry of skeletal muscle from ADR and other mouse models of human
      muscle disease demonstrate that the absence of ClC-1 chloride channel is a defect
      specific to ADR mice.

PMID- 7721816
TI  - Purification of apolipoprotein E attenuates isoform-specific binding to beta
      amyloid.
AB  - Apolipoprotein E (apoE), particularly the e4 allele, is genetically linked to the
      incidence of Alzheimer's disease. In vitro, apoE has been shown to bind beta
      amyloid (A beta), an amyloidogenic peptide that aggregates to form the primary
      component of senile plaques. In previous work, we demonstrated that apoE3 from
      tissue culture medium binds to A beta with greater avidity than apoE4 (LaDu, M.
      J., Falduto, M. T., Manelli, A. M., Reardon, C. A., Getz, G. S., and Frail, D. E.
      (1994) J. Biol. Chem. 269, 23403-23406). This is in contrast to data using
      purified apoE isoforms as substrate for A beta (Strittmatter, W. J., Weisgraber,
      K. H., Huang, D. Y., Dong, L.-M., Salvesen, G. S., Pericak-Vance, M., Schmechel,
      D., Saunders, A. M., Goldgaber, D., and Roses, A. D. (1993) Proc. Natl. Acad.
      Sci. U. S. A. 90, 8098-8102). Here we resolve this apparent discrepancy by
      demonstrating that the preferential binding of A beta to apoE3 is attenuated and
      even abolished with purification, a process that includes delipidation and
      denaturation. We compared the A beta binding capacity of unpurified apoE isoforms
      from both tissue culture medium and intact human very low density lipoproteins
      with that of apoE purified from these two sources. The interaction of human A
      beta-(1-40)-peptide and apoE was analyzed by nonreducing SDS-polyacrylamide gel
      electrophoresis followed by Western immunoblotting for either A beta or apoE
      immunoreactivity. While the level of the apoE3.A beta complex was approximately
      20-fold greater compared with the apoE4.A beta complex in unpurified conditioned
      medium, apoE3 and apoE4 purified from this medium bound to A beta with comparable
      avidity. Moreover, using endogenous apoE on very low density lipoproteins from
      plasma of apoE3/3 and apoE4/4 homozygotes, apoE3 was again a better substrate for
      A beta than apoE4. However, apoE purified from these plasma lipoproteins
      exhibited little isoform specificity in binding to A beta. These results suggest
      that native preparations of apoE may be a more physiologically relevant substrate
      for A beta binding than purified apoE and further underscore the importance of
      subtle differences in apoE conformation to its biological activity.

PMID- 7721817
TI  - Mechanism of acceleration of antithrombin-proteinase reactions by low affinity
      heparin. Role of the antithrombin binding pentasaccharide in heparin rate
      enhancement.
AB  - The role of the sequence-specific pentasaccharide region of high affinity heparin
      (HAH) in heparin acceleration of antithrombin-proteinase reactions was elucidated
      by determining the accelerating mechanism of low affinity heparin (LAH) lacking
      this sequence. LAH was shown to be free of HAH (< 0.001%) from the lack of
      exchange of added fluorescein-labeled HAH into LAH after separating the
      polysaccharides by antithrombin-agarose chromatography. Fluorescence titrations
      showed that LAH bound to antithrombin with a 1000-fold weaker affinity (KD 19 +/-
      6 microM) and 5-6-fold smaller fluorescence enhancement (8 +/- 3%) than HAH. LAH
      accelerated the antithrombin-thrombin reaction with a bell-shaped dependence on
      heparin concentration resembling that of HAH, but with the bell-shaped curve
      shifted to approximately 100-fold higher polysaccharide concentrations and with a
      approximately 100-fold reduced maximal accelerating effect. Rapid kinetic studies
      indicated these differences arose from a reverse order of assembly of an
      intermediate heparin-thrombin-antithrombin ternary complex and diminished ability
      of LAH to bridge antithrombin and thrombin in this complex, as compared to HAH.
      By contrast, LAH and HAH both accelerated the antithrombin-factor Xa reaction
      with a simple saturable dependence on heparin or inhibitor concentrations which
      paralleled the formation of an antithrombin-heparin binary complex. The maximal
      accelerations of the two heparins in this case correlated with the inhibitor
      fluorescence enhancements induced by the polysaccharides, consistent with the
      accelerations arising from conformational activation of antithrombin. 1H NMR
      difference spectroscopy of antithrombin complexes with LAH and HAH and
      competitive binding studies were consistent with LAH accelerating activity being
      mediated by binding to the same site on the inhibitor as HAH. These results
      demonstrate that LAH accelerates antithrombin-proteinase reactions by bridging
      and conformational activation mechanisms similar to those of HAH, with the
      reduced magnitude of LAH accelerations resulting both from a decreased
      antithrombin affinity and the inability to induce a full activating
      conformational change in the inhibitor.

PMID- 7721818
TI  - Cyclic GMP-dependent protein kinase blocks pertussis toxin-sensitive hormone
      receptor signaling pathways in Chinese hamster ovary cells.
AB  - cGMP-dependent protein kinase (cGMP kinase) has been implicated in the regulation
      of the cytosolic calcium level ([Ca2+]i). In Chinese hamster ovary (CHO) cells
      stably transfected with the cGMP kinase I alpha (CHO-cGK cells), cGMP kinase
      suppressed the thrombin-induced increase in inositol 1,4,5-trisphosphate and
      [Ca2+]i (Ruth, P., Wang, G.-X., Boekhoff, I., May, B., Pfeifer, A., Penner, R.,
      Korth, M., Breer, H., and Hofmann, F. (1993) Proc. Natl. Acad. Sci. U. S. A. 90,
      2623-2627). Cholecystokinin activated intracellular calcium release via a
      pertussis toxin (PTX)-insensitive pathway in CHO-cGK cells. cGMP kinase did not
      attenuate the CCK-stimulated [Ca2+]i. In contrast, cGMP kinase suppressed calcium
      influx stimulated by insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) via
      PTX-sensitive pathways. The effects of PTX and cGMP kinase on [Ca2+]i were not
      additive. 8-Bromo-cGMP had no effect on [Ca2+]i stimulated by IGF-1 or IGF-2 in
      wild type CHO cells. These results suggested that cGMP kinase inhibited the
      different signaling pathways by the phosphorylation of a PTX-sensitive G protein.
      cGMP kinase phosphorylated the alpha subunits of Gi1, Gi2, and Gi3 in vitro.
      Phosphorylation stoichiometry was 0.4 mol of phosphate/mol of G alpha i1 after
      reconstitution of heterotrimeric Gi1 in phospholipid vesicles. The alpha subunit
      of Gi was also phosphorylated in vivo. These results show that cGMP kinase blocks
      transduction of distinct hormone pathways that signal via PTX-sensitive Gi
      proteins.

PMID- 7721819
TI  - Sensitization of calcium-induced calcium release by cyclic ADP-ribose and
      calmodulin.
AB  - Cyclic ADP-ribose (cADPR) is emerging as an endogenous regulator of Ca2+-induced
      Ca2+ release (CICR), and we have recently demonstrated that its action is
      mediated by calmodulin (CaM) (Lee, H. C., Aarhus, R., Graeff, R., Gurnack, M. E.,
      and Walseth, T. F. (1994) Nature 370, 307-309). In this study we show by
      immunoblot analyses that the protein factor in sea urchin eggs responsible for
      conferring cADPR sensitivity to egg microsomes was CaM. This was further
      supported by the fact that bovine CaM was equally effective as the egg factor. In
      contrast, plant CaM was only partially active even at 10-20-fold higher
      concentrations. This exquisite specificity was also shown by binding studies
      using 125I-labeled bovine CaM. The effectiveness of various CaMs (bovine >
      spinach > wheat germ) in competing for the binding sites was identical to their
      potency in conferring cADPR sensitivity to the microsomes. A comparison between
      bovine and wheat germ CaM in competing for the sites suggests only 10-14% of the
      total binding was crucial for the activity. Depending on the CaM concentration,
      the sensitivity of the microsomes to cADPR could be changed by several orders of
      magnitude. The requirement for CaM could be alleviated by raising the divalent
      cation concentration with Sr2+. Results showed that CaM, cADPR, and caffeine all
      act synergistically to increase the divalent cation sensitivity of the CICR
      mechanism. The combined action of any of the three agonists was sufficient to
      sensitize the mechanism so much that even the nanomolar concentration of ambient
      Ca2+ was enough to activate the release. Unlike the CICR mechanism, the
      microsomal inositol 1,4,5-trisphosphate-sensitive Ca2+ release showed no
      dependence on CaM. Using an antagonist of CaM, W7, it was demonstrated that the
      cADPR-but not the inositol 1,4,5-trisphosphate-dependent release mechanism could
      be blocked in live sea urchin eggs. These results indicate cADPR can function as
      a physiological modulator of CICR and, together with CaM, can alter the
      sensitivity of the release mechanism to divalent cation by several orders of
      magnitude.

PMID- 7721820
TI  - An internalization motif is created in the cytoplasmic domain of the transferrin
      receptor by substitution of a tyrosine at the first position of a predicted tight
      turn.
AB  - Receptors are internalized from the plasma membrane at approximately 10 times the
      rate of bulk membrane. The predominant model for the motif that promotes rapid
      internalization proposes a requirement for a tyrosine located in the first
      position of a tight turn. In this report we show that an internalization motif
      can be created de novo by substituting a tyrosine for the first or last residues
      of a tetrapeptide GDNS (residues 31-34) that is predicted to form a tight turn
      within the cytoplasmic domain of the human transferrin receptor. These
      substitutions restore wild-type levels of internalization to transferrin
      receptors that are poorly internalized due to missense mutations in the native
      internalization motif. The introduction of a tyrosine at the first or last
      position of the GDNS tetrapeptide in a transferrin receptor containing an
      unmodified wild-type internalization motif significantly increases the
      internalization rate above that of the wild-type receptor. Our results indicate
      that a functional novel internalization motif can be created by placing specific
      aromatic amino acids within the overall structure of an existing beta-turn in a
      cytoplasmic domain of a receptor.

PMID- 7721821
TI  - Energetics of ATP dissociation from the mitochondrial ATPase during oxidative
      phosphorylation.
AB  - The dissociation constant (KdATP) for ATP bound in the high affinity catalytic
      site of membrane-bound beef heart mitochondrial ATPase (F1) was calculated from
      the ratio of the rate constants for the reverse dissociation step (k-1) and the
      forward binding step (k+1). k-1 for ATP bound to submitochondrial particles or to
      submitochondrial particles washed with KCl so as to activate ATPase activity was
      accelerated by about five orders of magnitude during respiratory chain-linked
      oxidations of NADH. In the presence of NADH and 0.1 mM ADP, k-1 increased more
      than six orders of magnitude. These energy-dependent dissociations of ATP were
      sensitive to the uncoupler carbonyl cyanide p-trifluoromethyloxyphenylhydrazone.
      Only small changes in k+1 were observed in the presence of NADH or NADH and ADP.
      KdATP at 23 degrees C in the absence of NADH and ADP was 10(-12) M, in the
      presence of NADH, 3 microM, and in the presence of NADH and 0.1 mM ADP, 60
      microM. Thus, the dissociation of ATP during the transition from non-energized to
      energized states was, under these conditions, accompanied by observed free energy
      changes of 8 and 9.7 kcal/mol, respectively.

PMID- 7721822
TI  - Inhibition of mammalian squalene synthetase activity by zaragozic acid A is a
      result of competitive inhibition followed by mechanism-based irreversible
      inactivation.
AB  - Squalene synthetase (SQS, EC 2.5.1.21) catalyzes the first committed step in the
      formation of cholesterol and thus represents an ideal site for selectively
      inhibiting sterol formation. Previous studies have demonstrated that the fungal
      metabolite, zaragozic acid A (ZGA-A), inhibits SQS activity by mimicking the
      substrate farnesyl pyrophosphate, the reaction intermediate presqualene
      pyrophosphate, or both, through a process that confers increased apparent potency
      in the presence of reduced enzyme concentrations, an observation consistent with
      either tight binding reversible competitive inhibition or mechanism-based
      irreversible inactivation. The studies outlined in this report provide multiple
      lines of evidence indicating that ZGA-A acts as a mechanism-based irreversible
      inactivator of SQS. 1) Inhibition of SQS by ZGA-A is dependent on the [SQS]
      present in the incubation reaction, and this inhibition is time-dependent and
      follows pseudo-first order reaction kinetics, exhibiting kobs values that range
      between 2 x 10(-4)/s and 23 x 10(-4)/s for [ZGA-A] within the log-linear range of
      the inhibition curve, and a bimolecular rate constant of 2.3 x 10(5) M-1s-1.2)
      SQS activity is titratable by ZGA-A, such that for each [ZGA-A] evaluated,
      inactivation exhibits a threshold [SQS] whereby enzyme activity at lower [SQS] is
      totally inhibited. 3) Time-dependent inactivation exhibits saturation kinetics
      with a Km for the process of 2.5 nM, which is approximately equal to the IC50 for
      SQS inhibition under these conditions, suggesting that inactivation results from
      selective modification of a functional group of the enzyme active center rather
      than from a nonspecific bimolecular reaction mechanism and that most, if not all
      of the inhibition results from irreversible inactivation. 4) Saturable, time
      dependent inactivation occurs with similar inactivation kinetics for both the
      microsomal and trypsin-solubilized forms of the enzyme, indicating that
      irreversible inactivation by ZGA-A is not a consequence of membrane modification
      but is a direct effect of the inhibitor on the enzyme. 5) Inactivation is
      biphasic, exhibiting a rapid ("burst") phase followed by a second, pseudo-first
      order phase, similar to that previously noted for irreversible inactivators in
      other enzyme systems, and occurs even in the presence of 5 mM concentrations of
      the nucleophylic scavenger dithiothreitol, suggesting that the reaction between
      ZGA-A and SQS occurs at or near the active center prior to diffusion of reactive
      species out of the catalytic cleft. 6) Inactivation can be prevented through
      competition with the substrate, farnesyl pyrophosphate, further identifying the
      active center as the site of modification.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7721823
TI  - Co-expressed complementary fragments of the human red cell anion exchanger (band
      3, AE1) generate stilbene disulfonate-sensitive anion transport.
AB  - We have constructed cDNA clones encoding various portions of the human red cell
      anion transporter (band 3), a well characterized integral membrane protein with
      up to 14 transmembrane segments. The biosynthesis, stability, cell surface
      expression, and functionality of these band 3 fragments were investigated by
      expression from the cRNAs into microsomal membranes using the reticulocyte cell
      free translation system and in Xenopus oocytes. Co-expression of the pairs of
      recombinants encoding the first 8 and last 6 transmembrane spans (8 + 6) or the
      first 12 and last 2 spans (12 + 2) of band 3 generated stilbene disulfonate
      sensitive anion transport in oocytes. When the pairs of fragments 8 + 6 or 12 + 2
      were co-expressed with glycophorin A (GPA), translocation to the plasma membrane
      of the fragment corresponding to the first 12 or the first 8 transmembrane spans
      was greater than in the absence of GPA. Only the fragment encoding the first 12
      transmembrane spans showed GPA-dependent translocation when expressed in the
      absence of its complementary fragment. A truncated form of band 3 encoding all 14
      transmembrane spans but lacking the carboxyl-terminal 30 amino acids of the
      cytoplasmic tail did not induce anion transport activity in oocytes and was not
      translocated to the plasma membrane but appeared to be degraded in oocytes. Our
      results suggest that there is no single signal for the insertion of the different
      transmembrane spans of band 3 into membranes and that the integrity of the loops
      between transmembrane spans 8-9 or 12-13 is not essential for anion transport
      function. Our data also suggest that a region of transmembrane spans 9-12 of band
      3 is involved in the process by which GPA facilitates the translocation of band 3
      to the surface.

PMID- 7721824
TI  - A novel nerve growth factor-responsive element in the stromelysin-1 (transin)
      gene that is necessary and sufficient for gene expression in PC12 cells.
AB  - Stromelysin-1 (ST-1) is an extracellular matrix metalloproteinase whose
      expression is transcriptionally regulated by nerve growth factor (NGF) in the
      PC12 rat pheochromocytoma cell line. In this paper, we define sequences in the
      proximal ST-1 promoter that contain a novel NGF-responsive element(s). We show
      that this cis-acting promoter element can bind nuclear proteins from both
      untreated and NGF-treated PC12 cells in a specific and saturable manner and is
      sufficient to confer NGF-inducibility to a heterologous promoter. At least a
      portion of this NGF-responsive element lies within a 12-base pair region between
      positions -241 and -229 of the ST-1 promoter and bears no sequence homology to
      other known transcriptional elements. In contrast to what has been reported for
      fibroblasts, an AP1 site centered around position -68 does not seem to be
      involved in the growth factor regulation of ST-1 in PC12 cells. These results
      suggest that the NGF regulation of ST-1 gene expression involves different
      promoter elements, and possibly different transcription factors, from that
      described for ST-1 induction by other growth factors.

PMID- 7721825
TI  - Identification of the major tyrosine kinase substrate in signaling complexes
      formed after engagement of Fc gamma receptors.
AB  - We have recently identified the protein product of the c-cbl proto-oncogene as an
      SH3 binding protein expressed in macrophages. To investigate the possibility that
      p120c-cbl is involved in signaling pathways initiated by cell surface receptors
      for IgG (Fc gamma R), lysates of HL60 cells were examined for tyrosine
      phosphorylation of p120c-cbl upon Fc gamma R engagement. Our findings demonstrate
      that p120c-cbl is tyrosine-phosphorylated upon Fc gamma R engagement and that
      this molecule represents the major tyrosine kinase substrate in this signaling
      pathway. Protein complexes containing p120c-cbl, p72syk, and p56lyn were observed
      either in resting or activated cells. In vitro studies showed that the direct
      association between p120c-cbl and p56lyn was mediated by the SH3 domain of
      p56lyn.

PMID- 7721826
TI  - Interleukin-8 receptor beta. The role of the carboxyl terminus in signal
      transduction.
AB  - Two interleukin-8 (IL-8) receptors, alpha and beta, have been identified and
      cloned. Both receptors are thought to transduce signals by coupling to GTP
      binding proteins. The aim of this study is to determine whether the carboxyl
      terminus (C') of IL-8 receptor beta (IL-8R beta) is involved in signaling in
      response to IL-8. We have constructed a number of IL-8R beta genes that encode
      truncated forms of the IL-8R beta. The deletions consisted of amino acids 349
      355, 336-355, 325-355, and 317-355 (termed beta 2, beta 3, beta 4, and beta 5,
      respectively). 293 human embryonic kidney cells were transfected with the wild
      type IL-8R beta (beta 1) and with these mutants. Cells transfected with the
      mutated receptors expressed the receptors and bound IL-8 with the same high
      affinity as cells transfected with the wild type receptor. The capacity of the
      mutated receptors to convey functional signals was evaluated by comparing the
      chemotaxis index of cells expressing the C'-truncated receptors to the index of
      cells expressing the wild type receptor. The results indicate that while cells
      expressing beta 1, beta 2, beta 3, and beta 4 were chemoattracted in response to
      IL-8, cells expressing beta 5 did not migrate in response to IL-8 stimulation.
      Therefore, the data suggest that amino acids 317-324 are involved in signaling by
      IL-8R beta.

PMID- 7721827
TI  - Sequence-dependent primer synthesis by the herpes simplex virus helicase-primase
      complex.
AB  - The herpes simplex virus helicase-primase complex, a heterotrimer of the UL5,
      UL8, and UL52 proteins, displays a single predominant site of primer synthesis on
      phi X174 virion DNA (Tenney, D. J., Hurlburt, W. W., Micheletti, P. M., Bifano,
      M., and Hamatake, R. K. (1994) J. Biol. Chem. 269, 5030-5035). This site was
      mapped and found to be deoxycytosine-rich, directing the synthesis of a primer
      initiating with several guanine residues. The size and sequence requirements for
      primer synthesis were determined using oligonucleotides containing variations of
      the predominant template. Although the efficiency of primer synthesis on
      oligonucleotides was influenced by template size, it was absolutely dependent on
      nucleotide sequence. Conversely, the ATPase activity on oligonucleotide templates
      was dependent on template size rather than nucleotide sequence. Furthermore, only
      oligonucleotides containing primase templates were inhibitory in a coupled
      primase-polymerase assay using phi X174 DNA as template, suggesting that primer
      synthesis or primase turnover is rate-limiting. Additionally, stimulation of
      helicase-primase by the UL8 component and that by the ICP8 protein were shown to
      differ mechanistically using different templates: the UL8 component stimulated
      the rate of primer synthesis on phi X174 virion DNA and oligonucleotide
      templates, while ICP8 stimulation occurred only on phi X174 virion DNA.

PMID- 7721828
TI  - ATP-dependent regulation of sodium-calcium exchange in Chinese hamster ovary
      cells transfected with the bovine cardiac sodium-calcium exchanger.
AB  - Chinese hamster ovary cells expressing the bovine cardiac Na/Ca exchanger were
      treated with ouabain to increase [Na+]i and stimulate Ca2+ influx by Na/Ca
      exchange. Depletion of cellular ATP inhibited 45Ca uptake by 40% or more and
      reduced the half-maximal Na+ concentration for inhibition of 45Ca uptake from 90
      to 55 mM. ATP depletion also reduced the rate of rise in [Ca2+]i when [Na+]o was
      reduced and inhibited the decline in [Ca2+]i when high [Na+]o was restored. The
      effects of ATP depletion were either absent or reduced in cells expressing a
      mutant exchanger missing most of the cytosolic hydrophilic domain. We were unable
      to detect a phosphorylated form of the exchanger in immunoprecipitates from 32P
      labeled cells. ATP depletion caused a breakdown in the actin cytoskeleton of the
      cells. Treatment of the cells with cytochalasin D mimicked the effects of ATP
      depletion on the [Na+] inhibition profile for 45Ca uptake. Thus, ATP depletion
      inhibits both the Ca2+ influx and Ca2+ efflux modes of Na/Ca exchange, and may
      alter the competitive interactions of extracellular Na+ and Ca2+ with the
      transporter. The latter effect appears to be related to changes in the actin
      cytoskeleton.

PMID- 7721829
TI  - Uptake of exogenous sn-1-acyl-2-lyso-phosphatidylinositol into HeLa S3 cells.
      Reacylation on the cell surface and metabolism to
      glucosaminyl(acyl)phosphatidylinositol.
AB  - A HeLa S3 subline is unusual in accumulating relatively large amounts of
      glucosaminyl(acyl)phosphatidylinositol (GlcN(acyl)PI), a derivative of
      phosphatidylinositol (PI) in which both GlcN and a fatty acid are linked to
      inositol hydroxyl groups (D. Sevlever, D. Humphrey, and T.L. Rosenberry,
      submitted for publication). This lipid is a proposed intermediate on the
      biosynthetic pathway for glycosyl-PI (GPI) anchors of membrane proteins. In this
      study we demonstrate for the first time that exogenous inositol phospholipids can
      enter this biosynthetic pathway and be metabolized to GlcN(acyl)PI. When HeLa S3
      cells were incubated for 24 h with exogenous PI or sn-1-acyl-2-lyso-phosphatidyl
      inositol (lyso-PI) labeled with 3H in the inositol group, 25-30% of the label was
      recovered in cell-associated lipids and most of the remaining 70-75% in
      hydrophilic metabolites in the medium. The predominant labeled lipid was PI, with
      smaller amounts of lyso-PI, phosphatidylinositol 4-phosphate (PIP), and
      GlcN(acyl)PI. Both exogenous lipid precursors gave the same distribution of
      labeled lipids, and a similar distribution was observed for endogenous inositol
      phospholipids metabolically labeled with [3H]inositol. Addition of excess
      inositol had no effect on the conversion of [3H]lyso-PI to [3H]GlcN(acyl)PI,
      indicating that the conversion did not result from breakdown to [3H]inositol
      followed by resynthesis. The cellular orientation of incorporated PI and lyso-PI
      was determined by incubating cells at 4 degrees C with PI-specific phospholipase
      C (PI-PLC). This enzyme cleaves only PI and lyso-PI on the outer leaflet of the
      cell membrane. After 24-h incubation with either precursor, only about 15% of
      cell-associated [3H]PI or [3H]lyso-PI was on the outer leaflet. However, more
      than 60% of the [3H]PI was on the outer leaflet after 1-h incubation with either
      precursor, suggesting that substantial sn-2 acylation of exogenous [3H]lyso-PI
      occurred in the outer leaflet. This suggestion was confirmed by examining labeled
      lipids in cells after uptake of [3H]lyso-PI at 4 degrees C. No transmembrane
      translocation of lyso-PI, PI phosphorylation, or PI glycosylation occurred at
      this temperature, but some sn-2 acylation was apparent and more than 90% of the
      [3H]PI formed was on the outer leaflet. These data indicate that sn-2 acylation
      can occur in the outer leaflet of the cell membrane, perhaps by transacylation
      from other cell surface phospholipids.

PMID- 7721830
TI  - Identification of a novel glycosaminoglycan core-like molecule. I. 500 MHz 1H NMR
      analysis using a nano-NMR probe indicates the presence of a terminal alpha-GalNAc
      residue capping 4-methylumbelliferyl-beta-D-xylosides.
AB  - beta-Xylosides compete with endogenous proteoglycan core proteins and act as
      alternate acceptors for synthesizing protein-free glycosaminoglycan chains. Their
      assembly on these alternate acceptors utilizes the same glycosyltransferases that
      make the protein-bound chains. Most studies using alternate acceptors focus on
      the production of sulfated glycosaminoglycan chains that are thought to be the
      major products. However, we previously showed that labeling melanoma cells with
      [6-3H]galactose in the presence of 4-methylumbelliferyl (MU) or p-nitrophenyl
      (pNP) beta-xylosides led to the synthesis of mostly di- to tetrasaccharide
      products including incomplete core structures. We have solved the structure of
      one of the previously unidentified products as, GalNAc alpha(1,4)GlcA
      beta(1,3)Gal beta(1,3)Gal beta(1,4)Xyl beta MU, based on compositional analysis
      by high performance liquid chromatography, fast atom bombardment, electrospray
      mass spectrometry, and one-dimensional and two-dimensional 1H NMR spectroscopy.
      The novel aspect of this molecule is the presence of a terminal alpha-Gal-NAc
      residue at a position that is normally occupied by beta-GalNAc in
      chondroitin/dermatan sulfate or by alpha-Glc-NAc in heparin or heparan sulfate
      chains. An alpha-GalNAc residue at this critical location may prevent further
      chain extension or influence the type of chain subsequently added to the common
      tetrasaccharide core.

PMID- 7721831
TI  - Identification of a novel glycosaminoglycan core-like molecule. II. Alpha-GalNAc
      capped xylosides can be made by many cell types.
AB  - The accompanying article (Manzi, A., Salimath, P. V., Spiro, R. C., Keifer, P.
      A., and Freeze, H. H. (1995) J. Biol. Chem. 270, 9154-9163) reported the complete
      structure of a novel molecule made by human melanoma cells incubated with 1 mM 4
      methylumbelliferyl-beta Xyl (Xyl beta MU). The product resembles a common
      pentasaccharide core region found in chondroitin/dermatan sulfate
      glycosaminoglycans, except that a terminal alpha-Gal-NAc residue is found in a
      location normally occupied by beta-GalNAc in these chains or alpha-GlcNAc in
      heparan sulfate chains. In this paper we show that several other human cancer
      cell lines and Chinese hamster ovary cells also make alpha-GalNAc-capped
      xylosides. The [6-3H]galactose-labeled Xyl beta MU product binds to immobilized
      alpha-GalNAc-specific lectin from Helix pomatia and the binding is competed by
      GalNAc, but not by Glc. Binding to the lectin is destroyed by digestion with
      alpha-N-acetylgalactosaminidase, but not beta-hexosaminidase. The nature of the
      aglycone influences the amount and relative proportion of this material made,
      with p-nitrophenyl-beta-xyloside being a better promoter of alpha-GalNAc
      terminated product than Xyl beta MU. This novel oligosaccharide accounts for 45
      65% of xyloside-based products made by both human melanoma and Chinese hamster
      ovary cells when they are incubated with 30 microM Xyl beta MU, but at 1 mM both
      the total amount and the proportion decreases to only 5-10%. In both cell lines
      this product is replaced by a corresponding amount of Sia alpha 2,3Gal beta 4Xyl
      beta MU. Preferential synthesis of the alpha-GalNAc-capped material at very low
      xyloside concentration argues that it is a normal biosynthetic product and not an
      experimental artifact. This pentasaccharide may be a previously unrecognized
      intermediate in glycosaminoglycan chain biosynthesis. Since this alpha-GalNAc
      residue occurs at a position that determines whether chondroitin or heparan
      chains are added to the acceptor, it may influence the timing, type, and extent
      of further chain elongation.

PMID- 7721832
TI  - cAMP-dependent protein kinase is necessary for increased NF-E2.DNA complex
      formation during erythroleukemia cell differentiation.
AB  - When murine erythroleukemia (MEL) cells are induced to differentiate by
      hexamethylene bisacetamide (HMBA), erythroid-specific genes are transcriptionally
      activated; however, transcriptional activation of these genes is severely
      impaired in cAMP-dependent protein kinase (protein kinase A)-deficient MEL cells.
      The transcription factor NF-E2, composed of a 45-kDa (p45) and an 18-kDa (p18)
      subunit, is essential for enhancer activity of the globin locus control regions
      (LCRs). DNA binding of NF-E2 and alpha-globin LCR enhancer activity was
      significantly less in HMBA-treated protein kinase A-deficient cells compared to
      cells containing normal protein kinase A activity; DNA binding of several other
      transcription factors was the same in both cell types. In parental cells, HMBA
      treatment and/or prolonged activation of protein kinase A increased the amount of
      NF-E2.DNA complexes without change in DNA binding affinity; the expression of p45
      and p18 was the same under all conditions. p45 and p18 were phosphorylated by
      protein kinase A in vitro, but the phosphorylation did not affect NF-E2.DNA
      complexes, suggesting that protein kinase A regulates NF-E2.DNA complex formation
      indirectly, e.g. by altering expression of a regulatory factor(s). Thus, protein
      kinase A appears to be necessary for increased NF-E2.DNA complex formation during
      differentiation of MEL cells and may influence erythroid-specific gene expression
      through this mechanism.

PMID- 7721833
TI  - Cloning and expression of a yeast gene encoding a protein with ATPase activity
      and high identity to the subunit 4 of the human 26 S protease.
AB  - The cloning, expression, and biochemical characterization of an essential gene of
      Saccharomyces cerevisiae that encodes for a new member of the TBP1-like subfamily
      of putative ATPases are described. The protein is 72% identical at the amino acid
      level to subunit four (S4) of the human 26 S protease and 73% identical to
      Schizosaccharomyces pombe MTS2 gene product. The purified, recombinant protein,
      designated Yhs4p, has an estimated molecular mass of 49 kDa and exhibits a Mg(2+)
      dependent ATPase activity with nucleotide specificity and Km for ATP similar to
      those exhibited by the human 26 S protease. The observed ATPase activity was
      reduced by 73% upon the introduction of point mutation K229Q in the "P-loop"
      domain of the ATP-binding site relative to the nonmutated form of the protein.
      This is the first direct biochemical evidence supporting the putative ATPase
      activity of a member of the TBP1-like subfamily. Furthermore, the experimental
      results demonstrate a regulatory function for the amino-terminal region of the
      molecule. The amino-terminal truncated form of Yhs4p lacking two clusters of
      positively charged amino acids exhibits a greater ATPase activity. The ATPase
      activity of both the truncated and complete forms of Yhs4p is stimulated by
      polyanions. Polylysine partially inhibits the ATPase activity of the amino
      terminal truncated form having no observable effect on the complete protein. N
      Ethylmaleimide inhibits the ATPase activity of both forms of Yhs4p. We propose
      that Yhs4p ATPase may play an essential role in the regulatory function of the
      proteolytic activity of the yeast 26 S protease.

PMID- 7721834
TI  - Disulfide bond formation between the COOH-terminal domain of the beta subunits
      and the gamma and epsilon subunits of the Escherichia coli F1-ATPase. Structural
      implications and functional consequences.
AB  - A set of mutants of the Escherichia coli F1F0-type ATPase has been generated by
      site-directed mutagenesis as follows: beta E381C, beta S383C, beta E381C/epsilon
      S108C, and beta S383C/epsilon S108C. Treatment of ECF1 isolated from any of these
      mutants with CuCl2 induces disulfide bond formation. For the single mutants, beta
      E381C and beta S383C, a disulfide bond is formed in essentially 100% yield
      between a beta subunit and the gamma subunit, probably at Cys87 based on the
      recent structure determination of F1 (Abrahams, J. P., Leslie, A. G. W., Lutter,
      R., and Walker, J. E. (1994) Nature 370, 621-628). In the double mutants, two
      disulfide bonds are formed, again in essentially full yield, one between beta and
      gamma, the other between a beta and the epsilon subunit via Cys108. The same two
      cross-links are produced with CuCl2 treatment of ECF1F0 isolated from either of
      the double mutants. These results show that the parts of gamma around residue 87
      (a short alpha-helix) and the epsilon subunit interact with different beta
      subunits. The yield of covalent linkage of beta to gamma is nucleotide dependent
      and highest in ATP and much lower with ADP in catalytic sites. The yield of
      covalent linkage of beta to epsilon is also nucleotide dependent but in this case
      is highest in ADP and much lower in ATP. Disulfide bond formation between either
      beta and gamma, or beta and epsilon inhibits the ATPase activity of the enzyme in
      proportion to the yield of the cross-linked product. Chemical modification of the
      Cys at either position 381 or 383 of the beta subunit inhibits ATPase activity in
      a manner that appears to be dependent on the size of the modifying reagent. These
      results are as expected if movements of the catalytic site-containing beta
      subunits relative to the gamma and epsilon subunits are an essential part of the
      cooperativity of the enzyme.

PMID- 7721835
TI  - Surface-core relationships in human low density lipoprotein as studied by
      infrared spectroscopy.
AB  - The secondary structure of human apolipoprotein B at 37 degrees C is estimated to
      be 24% alpha-helix, 23% beta-sheet, 6% beta-turns, 24% unordered structure, and
      24% "beta-strands," characterized by a band around 1618 cm-1, and consistent with
      extended string-like chains in contact with the lipid moiety not forming beta
      sheets. When cooled to a temperature below the cholesteryl ester transition at 30
      degrees C, the ordering of the low density lipoprotein core results in reversible
      changes in the protein conformation, decreasing the apparent amount of alpha
      helix, beta-strand, and unordered structure below 30 degrees C and increasing
      beta-sheet and beta-turns. Lowering the ionic strength affects the core
      associated transitions, shifting their temperature from 30 to 20 degrees C, and
      modifying protein conformation below the transition. An additional thermal event
      is observed at 75 degrees C, leading to irreversible protein denaturation. In the
      broad temperature range between the 30 and 75 degrees C transitions,
      apolipoprotein B is stable toward both temperature and ionic strength changes.
      After thermal denaturation, the protein retains a certain degree of ordered
      structure.

PMID- 7721836
TI  - Antipeptide antibodies confirm the topology of the human norepinephrine
      transporter.
AB  - We have raised polyclonal antibodies (N6-28, L211-226, L371-384, and C590-607)
      against peptides corresponding to hydrophilic sequences of the human
      norepinephrine transporter (hNET). The antisera immunoprecipitated the [35S]Met
      labeled hNET. Antiserum L211-226, directed against a sequence of the putative
      second (large) extracellular loop of hNET, also immunoprecipitated the human
      dopamine transporter. Antisera N6-28 and C590-607, raised against a hNET peptide
      region of the N and the C termini, respectively, recognized a 58-kDa protein from
      transfected COS-7 cells expressing the hNET. This 58-kDa species represents a
      functional, glycosylated form of the hNET and not a degradation product.
      Tunicamycin treatment of transfected COS-7 cells as well as peptide-N-glycosidase
      F digestion of the transporter converted the 58-kDa species to a 50-kDa form,
      indicating that the latter represents the hNET core protein. In indirect
      immunofluorescence studies, our antisera confirmed the originally proposed
      topology of hNET. Antisera N6-28 and C590-607 detected hNET only in permeabilized
      cells. In contrast, antisera L211-226 and L371-384 directed against peptide
      sequences of the second and fourth putative extracellular loop displayed
      fluorescence signals with the intact cells.

PMID- 7721837
TI  - Action of mitochondrial DNA polymerase gamma at sites of base loss or oxidative
      damage.
AB  - Mitochondrial DNA is subject to oxidative damage generating 7,8-dihydro-8-oxo-2'
      deoxyguanosine (8-oxo-dG) residues and to spontaneous or induced base loss
      generating abasic sites. Synthetic oligonucleotides containing these lesions were
      prepared and used as templates to determine their effects on the action of
      Xenopus laevis DNA polymerase gamma. An analogue of an abasic site in DNA,
      tetrahydrofuran, was found to inhibit elongation by DNA polymerase gamma. When
      the DNA polymerase was able to complete translesional synthesis, a dA residue was
      incorporated opposite the abasic site. In contrast, elongation by DNA polymerase
      gamma was not inhibited by an 8-oxo-dG residue in the template strand. The
      polymerase inserted dA opposite 8-oxo-dG in approximately 27% of the extended
      products. The effects of these lesions on the 3'-->5' exonuclease proofreading
      activity of DNA polymerase gamma were also investigated. The 3'-->5' exonuclease
      activity excised any of the four normal bases positioned opposite either a
      tetrahydrofuran residue or 8-oxo-dG, suggesting that proofreading may not play a
      major role in avoiding misincorporation at abasic sites or 8-oxo-dG residues in
      the template. Thus, both of these lesions have the prospect of causing high rates
      of mutation during mtDNA replication.

PMID- 7721838
TI  - The disulfide folding pathway of human epidermal growth factor.
AB  - Human epidermal growth factor (EGF) contains three disulfides and 53 amino acids.
      Reduced/denatured EGF refolds spontaneously in vitro to acquire its native
      structure. The mechanism of this folding process has been elucidated by
      structural analysis of both acid and iodoacetate trapped intermediates. The
      results reveal that the folding is accompanied by a sequential flow of unfolded
      EGF (0-disulfide) through three groups of folding intermediates, namely 1
      disulfide, 2-disulfide, and 3-disulfide (scrambled) EGF isomers, to reach the
      native structure. Equilibrium occurs among isomers of each class of disulfide
      species, and the composition of intermediates appears to be highly heterogeneous.
      Together, at least 27 fractions of folding intermediates have been identified,
      but there exist only limited numbers of well populated species which constitute
      more than 80% of the total intermediates found during EGF folding. Six species of
      such well populated intermediates have been isolated, which included two 1-S-S,
      two 2-S-S, and two 3-S-S scrambled species. Their disulfide structures have been
      identified here. Both 1-S-S isomers are found to contain non-native disulfides.
      One of the 2-S-S species consists of two non-native disulfides and the other
      admits two native disulfides. Among the six disulfides of the two scrambled
      species, only one is native. Together, native disulfides constitute 25% of the
      total disulfides found in these six well populated intermediates. These results
      contrast sharply to those observed with bovine pancreatic trypsin inhibitor,
      which has shown that well populated folding intermediates consist of exclusively
      native disulfides (Weissman, J. S., and Kim, P. S. (1991) Science 253, 1386
      1393). We propose that well populated folding intermediates, regardless of
      whether they contain native or non-native disulfides, do not necessarily
      represent the productive species and specify the folding pathway. Furthermore,
      conditions influencing the efficiency of EGF folding have been investigated. It
      is demonstrated here that under optimized compositions of redox agents, including
      the use of cysteine/cystine and protein disulfide isomerase, the in vitro folding
      of EGF could be achieved quantitatively within 1 min.

PMID- 7721839
TI  - Copper and silver transport by CopB-ATPase in membrane vesicles of Enterococcus
      hirae.
AB  - The P-type ATPase, CopB, of Enterococcus hirae is required for the copper
      resistance displayed by this organism and thus was postulated to be a copper
      pump. Using 64Cu+ and 110mAg+, we here show ATP-driven copper and silver
      accumulation catalyzed by CopB in native inside-out membrane vesicles of E.
      hirae. CopB ATPase exhibited an apparent Km for Cu+ and Ag+ of 1 microM and for
      ATP of 10 microM. Transport was maximal at pH 6 and had an apparent Vmax of 0.07
      nmol.min-1.mg-1 for both copper and silver transport. Vanadate displayed a
      biphasic effect on transport: maximal inhibition was observed at 40 microM
      vanadate for copper transport and 60 microM for silver transport, respectively.
      At higher vanadate concentrations, these inhibitions were reversed. The CopB
      ATPase of E. hirae is thus a pump for the extrusion of monovalent copper and
      silver ions, with copper probably being the natural substrate.

PMID- 7721840
TI  - G120R, a human growth hormone antagonist, shows zinc-dependent agonist and
      antagonist activity on Nb2 cells.
AB  - Substitution of arginine for glycine at position 120 in native 22-kDa human
      growth hormone (hGH) results in an analogue, G120R, which is unable to dimerize
      the GH receptor and is widely used to probe the molecular mechanism of action of
      hGH. When acting on human GH receptors, G120R antagonizes several biological
      effects of hGH, but is itself inactive as an agonist. It has been reported that
      this mutant also antagonizes hGH activation of the rat or human prolactin (PRL)
      receptor in cell-based assays, with no agonist activity. We have now tested this
      mutant in a sensitive MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide)-ESTA (eluted stain assay) bioassay using rat PRL receptors in the Nb2
      cell line. We confirm that G120R acts as an efficient antagonist of native hGH,
      but show that it can also act as an agonist to generate intracellular signals
      leading to metabolic activation and proliferation of Nb2 cells. We have
      demonstrated an unusual sensitivity to the presence of zinc (Zn2+). In the
      absence of added Zn2+, G120R shows weak but full agonist activity in the
      bioassay, and this can be blocked by co-incubation with recombinant hGH-binding
      protein. G120R can therefore be utilized to discriminate between the molecular
      mechanisms of hGH interactions with its somatogenic and lactogenic receptors.
      Future studies with G120R in the rat may need to take account of its significant
      agonist effects on PRL receptors.

PMID- 7721841
TI  - Processing of ADP-ribosylated integrin alpha 7 in skeletal muscle myotubes.
AB  - Integrin alpha 7 is a major substrate in skeletal muscle cells for the cell
      surface, glycosylphosphatidylinositol-anchored, arginine-specific ADP
      ribosyltransferase. Since ADP-ribosylarginine hydrolase, the enzyme responsible
      for cleavage of the ADP-ribosylarginine bond and a component with the transferase
      of a putative ADP-ribosylation cycle, is cytosolic, the processing of ADP
      ribosylated integrin alpha 7 was investigated. Following incubation of
      differentiated mouse C2C12 myoblasts with [adenylate-32P]NAD and analysis by SDS
      polyacrylamide gel electrophoresis under reducing conditions, two [32P]ADP
      ribosylated forms of integrin alpha 7 were resolved. By pulse-chase and
      purification of the radiolabeled proteins on a laminin affinity column, it was
      demonstrated that a 105-kDa ADP-ribosylated form originated from a mono-ADP
      ribosylated 102-kDa form and represented integrin alpha 7 modified at more than
      one site. The additional site(s) of modification, utilized at higher NAD
      concentrations, were located in the 63-kDa N-terminal segment of integrin alpha
      7. Both [32P]ADP-ribosylated integrins were loosely associated with the
      cytoskeleton, bound to laminin affinity columns, and immunoprecipitated with
      antibodies to integrin beta 1. 32P label was rapidly removed from [32P]ADP
      ribosylated integrin alpha 7 at either site of modification, a process inhibited
      by free ADP-ribose or p-nitrophenylthymidine-5'-monophosphate, an alternative
      substrate of 5'-nucleotide phosphodiesterase. The processed integrin alpha 7 was
      unavailable for subsequent ADP-ribosylation, although the amount of surface
      integrin alpha 7 remained constant. During the processing, no loss of label was
      observed from integrin alpha 7 radiolabeled with [14C]NAD, containing 14C in the
      nicotinamide proximal ribose, consistent with degradation of the ADP-ribose
      moiety by a cell surface 5'-nucleotide phosphodiesterase. Thus, cell surface ADP
      ribosylation, in contrast to intracellular ADP-ribosylation, is not readily
      reversed by ADP-ribosylarginine hydrolase and seems to operate outside the
      postulated ADP-ribosylation cycle.

PMID- 7721842
TI  - Glycogen turnover in the isolated working rat heart.
AB  - The isolated working rat heart was adapted for simultaneous determination of
      glycogen synthesis and degradation using a dual isotope technique. After
      prelabeling of glycogen with [U-14C]glucose, glycogenolysis was determined
      continuously from the washout of 14CO2 plus [14C]lactate. Glycogen synthesis was
      determined during the same period from incorporation of [5-3H]glucose. In the
      absence of added hormones, hearts were predominantly glycogenolytic (1.5
      mumol/min/g, dry weight), and there was simultaneous synthesis (11% of the rate
      of glycogenolysis). The percentage of glucose taken up by the heart that could
      traverse the glycogen pool as a consequence of glycogen turnover was minor (5%).
      Insulin (10 milliunits/ml) predictably stimulated glycogen synthesis (3.6-fold)
      and nearly abolished glycogenolysis. Addition of glucagon (1 microgram/ml)
      increased contractile performance and initially stimulated glycogenolysis (3.8
      fold) until glycogen was largely depleted. Net tritium incorporation was
      unaffected by glucagon. Both hormones stimulated glycolytic flux from exogenous
      glucose (3H2O from [5-3H]glucose) as well as total glycolytic flux (3H2O plus
      glycogenolysis). The initial stimulation in total glycolytic flux with glucagon
      was largely from glycogen, explaining the lag in stimulation from exogenous
      glucose. The relationship between the specific radioactivity and amount of
      glycogen remaining after different degrees of glycogenolysis suggests that the
      preference of glycogenolysis for newly synthesized glycogen is only partial.

PMID- 7721843
TI  - Development of a receptor peptide antagonist to human gamma-interferon and
      characterization of its ligand-bound conformation using transferred nuclear
      Overhauser effect spectroscopy.
AB  - Polyclonal anti-idiotypic antibody raised to a synthetic discontinuous peptide
      derived from the human gamma-interferon (huIFN-gamma) sequence recognizes soluble
      human gamma-interferon receptor (Seelig, G. F., Prosise, W. W., and Taremi, S. S.
      (1994) J. Biol. Chem. 269, 358-363). We sought to use this reagent to identify a
      ligand-binding domain within IFN-gamma-receptor. To do this, the neutralizing
      anti-idiotypic antibody was used to probe overlapping linear peptide octamers of
      the extracellular domain of the huIFN-gamma receptor. A 22-amino-acid residue
      receptor segment 120-141 identified by the antibody was synthesized. CD and NMR
      analysis indicates that peptide 120-141 has no apparent secondary structure in
      water or in water containing 50% trifluoroethanol. The synthetic receptor peptide
      inhibited huIFN-gamma induced expression of HLA/DR antigen on Colo 205 cells with
      an approximate IC50 of 35 microM. Immobilized peptide specifically bound
      recombinant huIFN-gamma but did not bind human granulocyte-macrophage colony
      stimulating factor on a microtiter plate in a direct binding enzyme-linked
      immunosorbent assay. The binding results are supported by two-dimensional
      transferred nuclear Overhauser effect (TRNOE) NMR data obtained on the peptide in
      the presence of recombinant huIFN-gamma. Characterization of the conformation of
      the bound peptide by TRNOE suggests that this peptide assumes a distinct
      conformation. Intramolecular interactions within the bound peptide were detected
      at two non-contiguous regions and at a third region comprising a beta-turn formed
      by the sequence DIRK. We believe that this represents the structure of the
      receptor within the ligand-binding domain.

PMID- 7721844
TI  - Purification and characterization of a novel methyltransferase responsible for
      biosynthesis of halomethanes and methanethiol in Brassica oleracea.
AB  - A novel S-adenosyl-L-methionine:halide/bisulfide methyltransferase (EC 2.1.1.-)
      was purified approximately 1000-fold to apparent homogeneity from leaves of
      Brassica oleracea. The enzyme catalyzed the S-adenosyl-L-methionine-dependent
      methylation of the halides iodide, bromide, and chloride to monohalomethanes and
      of bisulfide to methanethiol. The dual function of the enzyme was demonstrated
      through co-purification of the halide- and bisulfide-methylating activities in
      the same ratio and by studies of competition between the alternative substrates
      iodide and bisulfide. The purification procedure included gel filtration, anion
      exchange chromatography, and affinity chromatography on adenosine-agarose.
      Elution of the protein from a chromatofocusing column indicated a pI value of
      4.8. The pH optimum of halide methylation (5.5-7.0) was different from that of
      bisulfide methylation (7.0-8.0). The molecular mass values for the native and
      denatured protein were 29.5 and 28 kDa, respectively, suggesting that the active
      enzyme is a monomer. The enzyme had the highest specificity constant for iodide
      and the next highest for bisulfide. Substrate interaction kinetics and product
      inhibition patterns were consistent with an Ordered Bi Bi mechanism.

PMID- 7721845
TI  - Construction of a human genomic library of clones containing poly(dG-dA).poly(dT
      dC) tracts by Mg(2+)-dependent triplex affinity capture. DNA polymorphism
      associated with the tracts.
AB  - Microsatellite DNA is a useful tool for detecting DNA polymorphisms among species
      or individuals, especially those among closely related individuals. We
      constructed a library of clones that contained poly(dG-dA).poly(dT-dC) tracts
      from human genomic DNA by Mg(2+)-dependent triplex DNA formation. Examination of
      triplex DNA formation in the presence of various metal ions Mg2+, Mn2+, or Zn2+
      revealed that the procedure worked best in the presence of Mg2+. Affinity
      enrichment was performed with AluI-digested chromosomal DNA mixed with
      biotinylated (dG-dA)17 in the presence of Mg2+. A library constructed after three
      cycles of affinity enrichment showed that over 80% of the clones contained at
      least one poly(dG-dA).poly(dT-dC) tract. Most of them contained a perfect (dG
      dA)n repeat 30-84 base pairs in length, while some contained variants such as (dC
      dT)10-(dC)-(dC-dT)9. Using the clones from the library as a probe, we detected
      DNA polymorphisms associated with the repeat length of the tracts in the Japanese
      population. We also detected a microsatellite instability among the tracts in a
      cancer tissue sample.

PMID- 7721846
TI  - DnaA protein is sensitive to a soluble factor and is specifically inactivated for
      initiation of in vitro replication of the Escherichia coli minichromosome.
AB  - DnaA protein loses the capacity to initiate chromosomal replication when treated
      with a soluble cell extract. This inactivation depends upon DNA and hydrolyzable
      ribonucleoside triphosphate. The extract does not affect the activities of other
      replicative proteins or the ability of DnaA to initiate replication of single
      stranded DNA that contains a DnaA-binding hairpin, indicating that the inhibitory
      effect is specific for the action of DnaA at oriC. Gel filtration experiments
      implicate a 150-kDa factor as being responsible. Mutant DnaAcos protein, which
      causes overinitiation in vivo, is insensitive to the inactivating factor,
      suggesting a requirement for this negative control in vivo. We propose that a
      soluble factor controls initiation through down-regulation of DnaA protein.

PMID- 7721847
TI  - Stimulation of transcription accompanying relaxation of chromatin structure in
      cells overexpressing high mobility group 1 protein.
AB  - We developed murine C-127 cell lines that stationarily overexpress high mobility
      group (HMG) proteins 1 and 2 by transfecting them with the bovine papilloma virus
      plasmid carrying their respective cDNA sequences. Using these cell lines, we
      examined the effects of these HMG proteins on the modulation of chromatin
      structure that accompanied transcription. The levels of HMG1 mRNA and protein in
      cells overexpressing HMG1 protein were enhanced about 7- and 3-fold,
      respectively, in comparison with control cells, whereas those in cells
      overexpressing HMG2 protein were enhanced about 17- and 9-fold. The expression of
      reporter genes transfected into the cells was enhanced approximately 2-fold in
      cells overexpressing HMG1, but not HMG2, in comparison with those in control
      cells, irrespective of the sources of the genes and promoters. The minichromosome
      derived from the reporter plasmid in cells overexpressing HMG1 protein was more
      susceptible to micrococcal nuclease digestion than those in cells overexpressing
      HMG2 protein and control cells. The enhanced accessibility to micrococcal
      nuclease was not restricted to the expressing gene and promoter but involved the
      entire minichromosome, suggesting that the enhancement of gene expression
      resulted from changes in the condensation of the entire minichromosomal region by
      HMG1 protein. Minichromosomes in cells overexpressing HMG contained enhanced
      amounts of the respective HMG proteins and simultaneously reduced amounts of
      histone H1s. These results suggest that HMG1 and -2 proteins have different
      functions in the modulation of chromatin structure, and that HMG1 protein may
      sustain the structure of the respective gene to ensure that its activity as a
      template is expressed fully. These observations on the modulation of chromatin
      structure accompanying gene transcription in cells overexpressing HMG protein may
      provide important information on the function of these proteins.

PMID- 7721848
TI  - Detection of a novel cell cycle-regulated kinase activity that associates with
      the amino terminus of the retinoblastoma protein in G2/M phases.
AB  - Recent genetic and functional evidence suggests that the amino terminus of the
      retinoblastoma (Rb) protein plays an important role in Rb-mediated growth
      suppression. To explore the mechanism(s) by which this portion of Rb may regulate
      cell growth, we have sought to characterize cellular proteins that associate with
      the Rb amino terminus using an in vitro protein-binding assay. Here we report
      that at least one such protein is a cell cycle-regulated Rb/histone H1 kinase
      (RbK) whose enzymatic and/or Rb association activity is most prevalent in G2/M
      phases of cells. In contrast to previously characterized cyclin-dependent and Rb
      associated kinases, such as cdk1 (cdc2) and cdk2, G2/M RbK 1) is not depleted by
      incubation with p13suc-beads, 2) is not detected with antisera against several Rb
      associated cyclins-cdks, and 3) associated with Rb via the Rb amino terminus, a
      region that is dispensable for interaction with other Rb-associated kinases. RbK
      is clearly distinct from previously characterized mitotic cdks since cyclin A
      cdc2, cyclin A-cdk2, cyclin B-cdc2, and cyclin B-cdk2 did not associate with the
      Rb amino terminus. Coprecipitation experiments with Rb antisera confirmed the
      association of Rb with a RbK-like kinase in metaphase-arrested cells in vivo.
      Interestingly, G2/M RbK did not appreciably associate with an analogous portion
      of p107, a Rb-related protein. Taken together, these data indicate that the Rb
      amino terminus specifically associates with a novel cell cycle-regulated kinase
      in late cell cycle stages.

PMID- 7721849
TI  - Spermine gates inward-rectifying muscarinic but not ATP-sensitive K+ channels in
      rabbit atrial myocytes. Intracellular substance-mediated mechanism of inward
      rectification.
AB  - The effect of spermine, a low molecular mass aliphatic amine with positive
      charges, on the strongly inwardly rectifying muscarinic K+ (KACh) channel was
      examined in rabbit atrial myocytes. In inside-out patch membranes, the single
      channel current-voltage relationship of KACh channels activated by guanosine 5'-3
      O-(thio)triphosphate became linear in the absence of intracellular Mg2+. The open
      probability (Po) of the channels did not show significant voltage dependence
      under these conditions. Spermine specifically reduced Po of outwardly flowing
      KACh channel currents without affecting the unitary current amplitude at
      depolarized potentials, but had no effect on inward KACh currents under
      hyperpolarization. This voltage dependence of Po of KACh channels in the presence
      of spermine resembled that normally observed in the whole cell or open cell
      attached configurations. Spermine (300 nM to 3 microM) also restored the
      relaxation of KACh currents which had been lost in the inside-out configuration.
      The effect of spermine was concentration-dependent with IC50 of approximately 10
      nM at +40 mV. The order of potency of polyamines in reducing Po at +40 mV was
      spermine > or = spermidine > putrescine > ornithine; arginine had no significant
      effect. Intracellular Mg2+ antagonized the effect of spermine. Neither the single
      channel conductance nor Po of the ATP-sensitive K+ channel, a weak inward
      rectifier, was affected by spermine. Because submillimolar concentrations of
      spermine and spermidine are available in the cytosol of most cells, these
      substances may be the unidentified intracellular gating factors for strong inward
      rectifiers such as KACh and IK1 channels.

PMID- 7721850
TI  - Evidence from electron paramagnetic resonance spectroscopy of the participation
      of radical intermediates in the reaction catalyzed by methylmalonyl-coenzyme A
      mutase.
AB  - Recombinant methylmalonyl-coenzyme A (CoA) mutase from Propionibacterium
      shermanii has been purified 20-fold to near homogeneity in a highly active form.
      Neither the apoenzyme (the form in which the enzyme is isolated) nor the
      holoenzyme (reconstituted with the cofactor, adenosylcobalamin) has an electron
      paramagnetic resonance (EPR) spectrum associated with it. However, the addition
      of either the substrate, methylmalonyl-CoA, or the product, succinyl-CoA, results
      in the appearance of a transient EPR signal. The signal has hyperfine features
      that indicate coupling of the unpaired electron to the cobalt nucleus. In the
      presence of [CD3]methylmalonyl-CoA, an EPR signal is also seen and is similar to
      that obtained in the presence of protiated substrate. Power saturation studies
      reveal the presence of two components, a slow relaxing species (with an apparent
      g value of 2.11) and a fast relaxing species (with an apparent g value of 2.14)
      that can be partially resolved at low temperature and high power. The EPR-active
      intermediate is observed under catalytic conditions and is approximately midway
      in its resonance position between a free radical and cob(II)alamin. It is
      postulated to represent an exchange-coupled cob(II)alamin ... free radical pair.
      The signal bears close resemblance to those observed with partially dehydrated
      polycrystalline adenosylcobalamin following laser photolysis (Ghanekar, V.D.,
      Lin, R.J., Coffman, R.E., and Blakley, R.L. (1981) Biochem. Biophys. Res. Commun.
      101, 215-221) and with the adenosylcobalamin-dependent ribonucleotide reductase
      under freeze-quench conditions (Orme-Johnson, W.H., Beinert, H., and Blakley,
      R.L. (1974) J. Biol. Chem. 249, 2338-2343). When cob(II)alamin is generated under
      noncatalytic conditions (i.e. in the presence of propionyl-CoA or by
      electrochemical reduction of enzyme-bound hydroxocob-(III)alamin), a different
      EPR signal is observed with g = 2.26 and g = 2.00, typical of base-on
      cob(II)alamin.

PMID- 7721851
TI  - Identification of tissue-type plasminogen activator-specific plasminogen
      activator inhibitor-1 mutants. Evidence that second sites of interaction
      contribute to target specificity.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of the
      plasminogen activators (PAs), tissue-type plasminogen activator (tPA), and
      urokinase-type plasminogen activator (uPA). A library of PAI-1 mutants containing
      substitutions at the P1 and P1' positions was screened for functional activity
      against tPA and thrombin. Several PAI-1 variants that were inactive against uPA
      in a previous study (Sherman, P. M., Lawrence, D. A., Yang, A. Y., Vandenberg, E.
      T., Paielli, D., Olson, S. T., Shore, J. D., and Ginsburg, D. (1992) J. Biol.
      Chem. 267, 7588-7595) had significant inhibitory activity toward tPA. This set of
      tPA-specific PAI-1 mutants contained a wide range of amino acid substitutions at
      P1 including Asn, Gln, His, Ser, Thr, Leu, Met, and all the aromatic amino acids.
      This group of mutants also demonstrated a spectrum of substitutions at P1'.
      Kinetic analyses of selected variants identified P1Tyr and P1His as the most
      efficient tPA-specific inhibitors, with second-order rate constants (ki) of 4.0 x
      10(5) M-1s-1 and 3.6 x 10(5) M-1s-1, respectively. Additional PA-specific PAI-1
      variants containing substitutions at P3 through P1' were constructed. P3Tyr-P2Ser
      P1Lys-P1'Trp and P3Tyr-P2Ser-P1Tyr-P1'Met had ki values of 1.7 x 10(6) M-1s-1 and
      2.5 x 10(6) M-1s-1 against tPA, respectively, but both were inactive against uPA.
      In contrast, P2Arg-P1Lys-P1'Ala inhibited uPA 74-fold more rapidly than tPA. The
      mutant PAI-1 library was also screened for inhibitory activity toward thrombin in
      the presence and absence of the cofactor heparin. While wild-type PAI-1 and
      several P1Arg variants inhibited thrombin in the absence of heparin, a number of
      variants were thrombin inhibitors only in the presence of heparin. These results
      demonstrate the importance of the reactive center residues in determining PAI-1
      target specificity and suggest that second sites of interaction between
      inhibitors and proteases can also contribute to target specificity. Finally, the
      PA-specific mutants described here should provide novel reagents for dissecting
      the physiological role of PAI-1 both in vitro and in vivo.

PMID- 7721852
TI  - The cellular internalization and degradation of hepatic lipase is mediated by low
      density lipoprotein receptor-related protein and requires cell surface
      proteoglycans.
AB  - Hepatic lipase (HL) and lipoprotein lipase (LpL) are structurally related
      lipolytic enzymes that have distinct functions in lipoprotein catabolism. In
      addition to its lipolytic activity, LpL binds to very low density lipoproteins
      and promotes their interaction with the low density lipoprotein receptor-related
      protein (LRP) (Chappell, D. A., Fry, G. L., Waknitz, M. A., Muhonen, L. E.,
      Pladet M. W., Iverius, P. H., and Strickland, D. K. (1993) J. Biol. Chem. 268,
      14168-14175). In vitro binding assays revealed that HL also binds to purified LRP
      with a KD of 52 nM. Its binding to LRP is inhibited by the 39-kDa receptor
      associated protein (RAP), a known LRP antagonist, and by heparin. 125I-Labeled HL
      is rapidly internalized and degraded by HepG2 cell lines, and approximately 70%
      of the cellular internalization and degradation is blocked by either exogenously
      added RAP or anti-LRP IgG. Mouse fibroblasts that lack LRP display a greatly
      diminished capacity to internalize and degrade HL when compared to control
      fibroblasts. These data indicate that LRP-mediated cellular uptake of HL accounts
      for a substantial portion of the internalization of this molecule. Proteoglycans
      have been shown to participate in the clearance of LpL, and consequently a role
      for proteoglycans in HL clearance pathway was also investigated. Chinese hamster
      ovary cell lines that are deficient in proteoglycan biosynthesis were unable to
      internalize or degrade 125I-HL despite the fact that these cells express LRP.
      Thus, the initial binding of HL to cell surface proteoglycans is an obligatory
      step for the delivery of the enzyme to LRP for endocytosis. A small, but
      significant, amount of 125I-HL was internalized in LRP deficient cells indicating
      that an LRP-independent pathway for HL internalization does exist. This pathway
      could involve cell surface proteoglycans, the LDL receptor, or some other
      unidentified surface protein.

PMID- 7721853
TI  - Increased alpha 1(I) procollagen gene expression in tight skin (TSK) mice
      myocardial fibroblasts is due to a reduced interaction of a negative regulatory
      sequence with AP-1 transcription factor.
AB  - The TSK mouse, a model of fibrosis, displays exaggerated connective tissue
      accumulation in skin and visceral organs including the heart. To study the
      mechanisms of myocardial fibrosis in TSK mice, we established several strains of
      TSK mice myocardial fibroblasts in culture and examined the regulation of
      collagen gene expression in these cells. These strains displayed increased
      collagen gene expression in comparison with myocardial fibroblasts established
      from normal mice. On an average, the TSK myocardial fibroblast cultures showed a
      4-fold increase in collagen synthesis and 4.4- and 3.6-fold increases,
      respectively, in alpha 1(I) and alpha 1(III) collagen mRNA steady state levels.
      The increased alpha 1(I) and alpha 1(III) collagen mRNA levels were mainly due to
      increased transcription rates (3.4- and 3.8-fold higher, respectively) of the
      respective genes. Furthermore, we showed that the up-regulation of alpha 1(I)
      procollagen gene transcription in TSK mice myocardial fibroblasts was due to the
      lack of the strong inhibitory influence of a regulatory sequence contained in the
      promoter region encompassing nucleotides -675 to -804. Nuclear extracts from TSK
      mice myocardial fibroblasts showed lower DNA binding activity to oligonucleotides
      spanning the mapped regulatory sequence as well as to a consensus AP-1 sequence,
      but not to a consensus SP-1 sequence, and supershift experiments with an AP-1
      antibody confirmed the interaction of these oligonucleotides with AP-1 protein.
      These observations indicate that a strong negative regulatory sequence contained
      within -0.675 to -0.804 kilobase of the alpha 1(I) procollagen promoter binds AP
      1 transcription factor and mediates inhibition of gene transcription in normal
      murine myocardial fibroblasts. The TSK mice myocardial fibroblasts lack this
      inhibitory control, due to lower available amounts and/or decreased binding
      activity to this inhibitory sequence, and hence display increased alpha 1(I)
      procollagen gene expression.

PMID- 7721854
TI  - Cloning and characterization of A-kinase anchor protein 100 (AKAP100). A protein
      that targets A-kinase to the sarcoplasmic reticulum.
AB  - Differential localization of the type II cAMP-dependent protein kinase (PKA) is
      achieved by interaction of the regulatory subunit (RII) with A-kinase anchor
      proteins (AKAPs). Anchoring is a likely means to adapt PKA for regulation of cAMP
      responsive events through colocalization of the kinase with preferred substrates.
      Using an interaction cloning strategy with an RII alpha protein probe, we have
      identified a 655-amino acid protein (named AKAP100). Recombinant AKAP100,
      expressed in Escherichia coli, binds RII alpha in a solid-phase overlay assay.
      The cellular and subcellular distribution of AKAP100 was analyzed by various
      methods. Northern blot analysis with the AKAP100 cDNA as a probe detected an 8
      kilobase message in some human tissues including various brain regions; however,
      the message was predominately expressed in cardiac and skeletal muscle. Anti
      AKAP100 antibodies confirmed expression in the rat cardiac and skeletal muscle
      cell lines, H9c2 and L6P, whereas immunohistochemical analysis revealed that
      AKAP100 was localized to the sarcoplasmic reticulum of both cell types. RII was
      also detected in these regions. AKAP100 was detected in preparations of RII
      purified from L6P cell extracts by cAMP-agarose affinity chromatography.
      Collectively, these results suggest that AKAP100 functions to maintain the type
      II PKA at the sarcoplasmic reticulum.

PMID- 7721855
TI  - Neurofilament protein heterotetramers as assembly intermediates.
AB  - Evidence is presented for the existence of a soluble heterotetramer containing
      the low and middle molecular weight neurofilament (NF) proteins, NF-L and NF-M,
      and one containing the low and high molecular weight proteins, NF-L and NF-H, and
      for their role in filament assembly. When a mixture of either pair of proteins
      was renatured in 2 M urea, 20 mM Tris, pH 7.2, a new band representing a complex
      was observed in native gel electrophoresis. No new band was observed with a
      mixture of NF-M and NF-H. Two-dimensional gel electrophoresis showed that
      treatment of the complexes with SDS caused them to dissociate into their
      constituent polypeptide chains. Native neurofilaments dissociated in 2 M urea
      into a mixture of LM and LH complexes. Titration of NF-L with NF-M indicated that
      complex formation was complete at an approximately equimolar ratio of the two
      proteins. The LM complex had a sedimentation coefficient, s20,w, of 4.4 S,
      consistent with a tetrameric structure. Dialysis of a solution of the LM complex
      against 50 mM 4-morpholineethanesulfonic acid, 0.17 M NaCl, pH 6.25, led to the
      formation of 10-nm filaments in good yield. These results suggest that NF protein
      heterooligomers are intermediates in NF assembly and disassembly.

PMID- 7721856
TI  - Silk gland factor-1 involved in the regulation of Bombyx sericin-1 gene contains
      fork head motif.
AB  - Silk gland factor-1 (SGF-1) regulates transcription of the Bombyx sericin-1 gene
      via interaction with the SA site. In this study, two related SGF-1 polypeptides
      of apparent molecular masses of 40 and 41 kDa were purified. Specific interaction
      of these proteins with the SA site was demonstrated by electrophoretic mobility
      shift and dimethyl sulfate methylation interference assays. The SGF-1 40-kDa
      protein was partially sequenced and characterized as a new member of the fork
      head/HNF-3 family. Several full-length cDNAs encoding the SGF-1 40-kDa and
      possibly also the 41-kDa proteins were cloned and sequenced. SGF-1 mRNA is
      expressed consistently with the presumed role of the SGF-1 protein product in
      regulating the sericin-1 gene. The SGF-1 protein contains putative
      transactivation domains. We conclude that the 40- and 41-kDa SGF-1 proteins
      affect transcription of the sericin-1 gene via binding to the SA site.

PMID- 7721857
TI  - Increased ubiquitin expression suppresses the cell cycle defect associated with
      the yeast ubiquitin conjugating enzyme, CDC34 (UBC3). Evidence for a noncovalent
      interaction between CDC34 and ubiquitin.
AB  - The yeast ubiquitin (Ub) conjugating enzyme CDC34 plays a crucial role in the
      progression of the cell cycle from the G1 to S phase. In an effort to identify
      proteins that interact with CDC34 we undertook a genetic screen to isolate genes
      whose increased expression suppressed the cell cycle defect associated with the
      cdc34-2 temperature-sensitive allele. From this screen, the poly-Ub gene UBI4 was
      identified as a moderately strong suppressor. The fact that the overexpression of
      a gene encoding a single Ub protein could also suppress the cdc34-2 allele
      indicated that suppression was related to the increased abundance of Ub. Ub
      overexpression was found to suppress two other structurally unrelated cdc34
      mutations, in addition to the cdc34-2 allele. In all three cases, suppression
      depended on the expression of Ub with an intact carboxyl terminus. Only the cdc34
      2 allele, however, could be suppressed by Ub with an amino acid substitution at
      lysine 48 which is known to be involved in multi-Ub chain assembly. Genetic
      results showing allele specific suppression of cdc34 mutations by various Ub
      derivatives suggested a specific noncovalent interaction between Ub and CDC34.
      Consistent with this prediction, we have shown by chemical cross-linking the
      existence of a specific noncovalent Ub binding site on CDC34. Together, these
      genetic and biochemical experiments indicate that Ub suppression of these cdc34
      mutations results from the combined contributions of Ub-CDC34 thiol ester
      formation and a noncovalent interaction between Ub and CDC34 and therefore
      suggest that the correct positioning of Ub on a surface of the ubiquitin
      conjugating enzyme is a requirement of enzyme function.

PMID- 7721858
TI  - Molecular cloning of the rat intestinal trefoil factor gene. Characterization of
      an intestinal goblet cell-associated promoter.
AB  - Intestinal trefoil factor (ITF) is a small peptide bearing the unique motif of
      intrachain disulfide bonds characteristic of the trefoil family. Previous work
      had localized expression of ITF primarily within goblet cells in the small and
      large bowel, making it a candidate gene for the study of the molecular basis of
      intestinal and goblet cell-specific gene expression. In order to study the
      regulation of ITF expression, we have cloned the rat ITF gene and sequenced 1.7
      kilobases of the 5'-flanking region. RNase protection analysis demonstrated a
      single transcriptional start site. Various lengths of the 5'-flanking region were
      linked to the reporter gene luciferase and transfected into the colon cancer cell
      lines LS174T and Caco-2, representing, respectively, cells with and without
      goblet cell-like phenotype. Expression in the goblet cell-like LS174T colon
      cancer cell line was nearly 10-fold greater than expression in Caco-2 cells which
      exhibit columnar enterocyte-like phenotype. The pattern of goblet cell-associated
      selective transcription required only 153 base pairs of the rat ITF 5'-flanking
      sequence. Transfection of a construct of human growth hormone under the control
      of the rat ITF promoter in the N2 subclone of HT-29 cells demonstrated expression
      of the reporter gene only in those cells exhibiting a goblet cell phenotype as
      assessed by expression of immunoreactive mucin. These initial studies of the 5'
      flanking region of the ITF gene demonstrate the presence of cis-regulatory
      elements capable of directing goblet cell specific expression.

PMID- 7721859
TI  - Genetic engineering of snake toxins. The functional site of Erabutoxin a, as
      delineated by site-directed mutagenesis, includes variant residues.
AB  - Using site-directed mutagenesis, we previously identified some residues that
      probably belong to the site by which Erabutoxin a (Ea), a sea snake toxin,
      recognizes the nicotinic acetylcholine receptor (AcChoR) (Pillet, L., Tremeau,
      O., Ducancel, F. Drevet, P., Zinn-Justin, S., Pinkasfeld, S., Boulain, J.-C., and
      Menez, A. (1993) J. Biol. Chem. 268, 909-916). We have now studied the effect of
      mutating 26 new positions on the affinity of Ea for AcChoR. The mutations are
      F4A, N5V, H6A, Q7L, S9G, Q10A, P11N, Q12A, T13V, T14A, K15A, T16A, delta S18,
      E21A, Y25F, Q28A, S30A, T35A, I36R, P44V, T45A, V46A, K47A, P48Q, I50Q, and S53A.
      Binding affinity decreases upon mutation at Gln-7, Gln-10 and to a lesser extent
      at His-6, Ser-9 and Tyr-25 whereas it increases upon mutation at Ile-36. Other
      mutations have no effect on Ea affinity. In addition, new mutations of the
      previously explored Ser-8, Asp-31, Arg-33, and Glu-38 better explain the
      functional role of these residues in Ea. The previous and present mutational
      analysis suggest that the "functional" site of Ea covers a homogeneous surface of
      at least 680 A2, encompassing the three toxin loops, and includes both conserved
      and variant residues. The variable residues might contribute to the selectivity
      of Ea for some AcChoRs, including those from fish, the prey of sea snakes.

PMID- 7721860
TI  - Properties of type II inositol polyphosphate 5-phosphatase.
AB  - We have isolated additional cDNA clones encoding type II inositol polyphosphate 5
      phosphatase (5-phosphatase II) resulting in a combined cDNA of 3076 nucleotides
      encoding a protein of 942 amino acids. The 5-phosphatase II hydrolyzed both
      Ins(1,4,5)P3 to Ins(1,4)P2 and the phospholipid PtdIns(4,5)P2 to PtdIns(4)P both
      in vitro and in vivo. There are two motifs highly conserved between types I and
      II 5-phosphatase and several other proteins presumed to be inositol phosphatases
      suggesting a possible role in catalysis. The type II 5-phosphatase also contains
      homology to several GTPase activating proteins although no such activity for 5
      phosphatase II was found. The predicted protein ends with the sequence CNPL,
      suggesting that it is isoprenylated as a mechanism for membrane attachment. We
      found evidence for isoprenylation by demonstrating incorporation of
      [3H]mevalonate into native but not C939S mutant 5-phosphatase II expressed in Sf9
      insect cells. Furthermore, we showed that membrane localization and the activity
      of 5-phosphatase II toward its lipid substrate PtdIns(4,5)P2 is reduced by
      eliminating 5-phosphatase II isoprenylation in the mutant C939S relative to the
      native enzyme.

PMID- 7721861
TI  - Expression, refolding, and autocatalytic proteolytic processing of the
      interleukin-1 beta-converting enzyme precursor.
AB  - The interleukin-1 beta-converting enzyme is a heterodimeric cysteine protease
      that is produced as a 45-kDa precursor. The full-length precursor form of the
      enzyme was expressed in Escherichia coli as insoluble inclusion bodies. Following
      solubilization and refolding of the 45-kDa protein, autoproteolytic conversion to
      a heterodimeric form containing 10- and 20-kDa subunits was observed. This enzyme
      had catalytic activity against both natural (interleukin-1 beta precursor) and
      synthetic peptide substrates. The inclusion of a specific inhibitor (SDZ 223-941)
      of the converting enzyme in the refolding mixture prevented proteolytic
      processing to the 10-/20-kDa form. Similarly, refolding under nonreducing
      conditions also prevented processing. Time course experiments showed that the 10
      kDa subunit was released from the 45-kDa precursor before the 20-kDa subunit,
      implying that the N-terminal portion of the precursor is released last and may
      play a regulatory role.

PMID- 7721862
TI  - c-Myb repression of c-erbB-2 transcription by direct binding to the c-erbB-2
      promoter.
AB  - The c-myb proto-oncogene product (c-Myb) is a transcriptional activator that can
      bind to the specific DNA sequences. Although c-Myb also represses an artificial
      promoter containing the Myb binding sites, natural target genes transcriptionally
      repressed by c-Myb have not been identified. We have found that the human c-erbB
      2 promoter activity is repressed by c-Myb or B-Myb in a chloramphenicol
      acetyltransferase co-transfection assay. Domain analyses of c-Myb suggested that
      Myb represses the c-erbB-2 promoter activity by competing with positive
      regulators of the c-erbB-2 promoter. In in vitro transcription assays, Myb
      proteins containing only the DNA binding domain could repress c-erbB-2 promoter
      activity. Two Myb binding sites in the c-erbB-2 promoter were critical for
      transcriptional repression by c-Myb. One of the two Myb binding sites overlaps
      the TATA box, and DNase I footprint analyses indicated that c-Myb can compete
      with TFIID. These results suggest that Myb-induced trans-repression of the c-erbB
      2 promoter partly involves competition between Myb and TFIID.

PMID- 7721863
TI  - Functional reconstitution of recombinant phospholamban with rabbit skeletal
      Ca(2+)-ATPase.
AB  - Phospholamban (PLB) is a small, transmembrane protein that resides in the cardiac
      sarcoplasmic reticulum (SR) and regulates the activity of Ca(2+)-ATPase in
      response to beta-adrenergic stimulation. We have used the baculovirus expression
      system in Sf21 cells to express milligram quantities of wild-type PLB. After
      purification by antibody affinity chromatography, the function of this
      recombinant PLB was tested by reconstitution with Ca(2+)-ATPase purified from
      skeletal SR. The results obtained with recombinant PLB were indistinguishable
      from those obtained with purified, canine cardiac PLB. In particular, PLB reduced
      the apparent calcium affinity of Ca(2+)-ATPase but had no effect on Vmax. At pCa
      6.8, PLB inhibited both calcium uptake and ATPase activity of Ca(2+)-ATPase by
      50%. This inhibition was fully reversed by addition of a monoclonal antibody to
      PLB, which mimics the physiological effects of PLB phosphorylation. Maximal PLB
      regulatory effects occurred at a molar stoichiometry of approximately 3:1,
      PLB/Ca(2+)-ATPase. We also investigated peptides corresponding to the two main
      domains of PLB. The membrane-spanning domain, PLB26-52, appeared to uncouple
      ATPase hydrolysis from calcium transport, even though the permeability of the
      reconstituted vesicles was not altered. The cytoplasmic peptide, PLB1-31, had
      little effect, even at a 300:1 molar excess over Ca(2+)-ATPase.

PMID- 7721864
TI  - Mapping of network-forming, heparin-binding, and alpha 1 beta 1 integrin
      recognition sites within the alpha-chain short arm of laminin-1.
AB  - Cell-interactive and architecture-forming functions are associated with the short
      arms of basement membrane laminin-1. To map and characterize these functions, we
      expressed recombinant mouse laminin-1 alpha-chain extending from the N terminus
      through one third of domain IIIb. This dumbbell-shaped glycoprotein (r alpha 1(VI
      IVb)'), secreted by mammalian cells, was found to possess three activities. 1)
      Laminin polymerization was quantitatively inhibited by recombinant protein,
      supporting an alpha-chain role for a three-short arm interaction model of laminin
      self-assembly. 2) r alpha 1(VI-IVb)' bound to heparin, and the activity was
      localized to a subfragment corresponding to domain VI by 125I-heparin blotting.
      3) PC12 rat pheochromocytoma cells adhered to, and rapidly extended branching
      neurites on, r alpha 1(VI-IVb)', with adhesion inhibited by alpha 1 and beta 1
      integrin chain-specific antibodies. The ability of anti-laminin antibody to block
      PC12 cell adhesion to laminin was selectively prevented by absorption with r
      alpha 1(VI-IVb)' or alpha-chain domain VI fragment. This active integrin
      recognition site could furthermore be distinguished from a second cryptic alpha 1
      beta 1-binding site exposed by heat treatment of fragment P1', a short arm
      fragment lacking globules. Thus, a polymer-forming, a heparin-binding, and the
      active alpha 1 beta 1 integrin-recognition site are all clustered at the end of
      the alpha-chain short arm, the latter two resident solely in domain VI.

PMID- 7721865
TI  - Coordinated induction of the ubiquitin conjugation pathway accompanies the
      developmentally programmed death of insect skeletal muscle.
AB  - The developmentally programmed cell death of abdominal intersegmental muscles in
      the tobacco hawk-moth Manduca sexta is coincident with a 10-fold induction of the
      polyubiquitin gene as a hormonally regulated event (Schwartz, L. M., Myer, A.,
      Kosz, L., Engelstein, M., and Maier, C. (1990) Neuron 5, 411-419). Solid phase
      immunochemical assays measuring intersegmental muscle pools of free and
      conjugated ubiquitin reveal that the induction of polyubiquitin mRNA is
      accompanied by a proportional increase in total ubiquitin polypeptide. Ubiquitin
      conjugate pools increase 10-fold at eclosion, during which loss of muscle protein
      mass is maximum. A smaller but measurable increase in ubiquitin conjugates is
      observed earlier in pupal development coincident with a modest enhanced
      degradation of myofibrillar proteins. Accumulation of ubiquitin conjugates is
      accompanied by induction in the pathway for polypeptide ligation, including the
      activating enzyme (E1), several carrier protein (E2) isoforms, and
      ubiquitin:protein isopeptide ligase (E3). Both accumulation of ubiquitin
      polypeptide and the enzymes of the conjugation pathway are subject to regulation
      by declining titers of the insect molting hormone 20-hydroxyecdysone, which
      signals onset of programmed cell death in the intersegmental muscles. Thus,
      programmed cell death within the intersegmental muscles is accomplished in part
      by stimulation of the ubiquitin-mediated degradative pathway through a
      coordinated induction of ubiquitin and the enzymes responsible for its
      conjugation to yield proteolytic intermediates. This suggests enzymes required
      for ubiquitin conjugation may represent additional genes recruited for
      developmentally programmed death.

PMID- 7721866
TI  - A yeast gene product, G4p2, with a specific affinity for quadruplex nucleic
      acids.
AB  - G4 nucleic acids are quadruplex structures involving guanine-rich sequences that
      form in vitro under moderate conditions. Experimental evidence exists supporting
      biological functions for these elements; however, direct demonstration of G4
      nucleic acids in vivo has not yet been achieved. Here we purify and characterize
      a yeast protein, G4p2, which has a specific affinity for G4 nucleic acids. G4p2
      binds equivalently to RNA and DNA in G4 form. The Keq for G4p2 binding to a G4
      DNA oligomer is 2.2 x 10(8) M-1 under near physiological conditions. We have
      cloned and sequenced the gene encoding G4p2 and have shown it to be identical to
      MPT4 and STO1. MPT4 was isolated in a screen for multicopy suppressors of
      staurosporine sensitivity in POP2 cells. Pop2 is a complex regulatory factor that
      participates, in part, in the repression of certain genes in the absence of
      glucose (Sakai, A., Chibazakura, T., Shimizu, Y., and Hishinuma, F. (1992)
      Nucleic Acids Res. 20, 6227-6233). STO1 was isolated as a multicopy suppressor of
      TOM1, an uncharacterized mutation that leads to temperature-sensitive cell cycle
      arrest at the G2/M boundary. Suppression of these mutations by G4p2 indicate this
      G4 nucleic acid binding protein may function in signal transduction pathways
      regulated by protein kinases, which control carbon source utilization, and in
      cell cycle progression.

PMID- 7721867
TI  - Rapidly forming apatitic mineral in an osteoblastic cell line (UMR 106-01 BSP).
AB  - This study evaluated a rapid biomineralization phenomenon exhibited by an
      osteoblastic cell line, UMR 106-01 BSP, when treated with either organic
      phosphates [beta-glycerophosphate (beta-GP), Ser-P, or Thr-P], inorganic
      phosphate (P(i)), or calcium. In a dose-dependent manner, these agents (2-10 mM)
      stimulated confluent cultures to deposit mineral in the cell layer (ED50 of
      approximately 4.6 mM for beta-GP (30 +/- 2 nmol Ca2+/microgram DNA) and
      approximately 3.8 mM (29 +/- 2 nmol Ca2+/microgram DNA) for P(i)) with a plateau
      in mineral formation by 20 h (ET50 approximately 12-15 h). beta-GP or P(i)
      treatment yielded mineral crystals having an x-ray diffraction pattern similar to
      normal human bone. Alizarin red-S histology demonstrated calcium mineral
      deposition in the extracellular matrix and what appeared to be intracellular
      paranuclear staining. Electron microscopy revealed small, needle-like crystals
      associated with fibrillar, extracellular matrix deposits and intracellular
      spherical structures. Mineral formation was inhibited by levamisole (ED50
      approximately 250 microM), pyrophosphate (ED50 approximately 1-10 microM),
      actinomycin C1 (500 ng/ml), cycloheximide (50 micrograms/ml), or brefeldin A (1
      microgram/ml). These results indicate that UMR 106-01 BSP cells form a bio
      apatitic mineralized matrix upon addition of supplemental phosphate. This process
      involves alkaline phosphatase activity, ongoing RNA and protein synthesis, as
      well as Golgi-mediated processing and secretion.

PMID- 7721868
TI  - Reduced numatrin/B23/nucleophosmin labeling in apoptotic Jurkat T-lymphoblasts.
AB  - Jurkat T-lymphoblasts were induced to undergo apoptosis by treatment with either
      EGTA (5 mM/24 h) or a high concentration of lovastatin (100 microM/48 h) to
      identify proteins that exhibited coordinate regulation between the two treatments
      and thus provide candidate proteins in the common apoptotic induction pathway. A
      pure population of apoptotic cells, as determined by morphology, "DNA laddering,"
      and flow cytometry, was obtained by Percoll density gradient centrifugation.
      Cells of increased buoyant density were clearly apoptotic by all criteria.
      Following this gradient centrifugation, the cells were labeled with
      [35S]methionine/cysteine, and lysates were separated by two-dimensional
      polyacrylamide gel electrophoresis. Surprisingly, the two-dimensional
      polyacrylamide gel electrophoresis patterns generated from the apoptotic cells
      did not differ dramatically from that of control cells. Thus, apoptotic Jurkat
      cells are able to synthesize new proteins and do not exhibit extensive
      proteolysis. Subsequent quantitative analysis revealed that only five proteins
      exhibited decreases in turnover that were common to the two treatments. No
      increases in protein turnover were able to be confirmed across the replicate
      experiments. One of the proteins that showed decreased labeling by both apoptotic
      inductions was an abundant nuclear protein with a pI of 5.1 and M(r) 40,000. This
      protein was identified as numatrin/B23/nucleophosmin (NPM) based on internal
      amino acid sequence, and this identity was confirmed by immunoblotting and mass
      spectrometry. NPM is implicated in a range of diverse cellular functions, but its
      role in apoptosis is unclear.

PMID- 7721869
TI  - The role of N-glycosylation in the targeting and activity of the GLYT1 glycine
      transporter.
AB  - To elucidate the role of N-glycosylation in the function of the high affinity
      glycine transporter GLYT1, we have investigated the effect of the glycosylation
      inhibitor tunicamycin as well as the effect of the disruption of the putative
      glycosylation sites by site-directed mutagenesis. SDS-polyacrylamide gel
      electrophoresis of proteins from GLYT1-transfected COS cells reveals a major band
      of 80-100 kDa and a minor one of 57 kDa. Treatment with tunicamycin produces a
      40% inhibition in transport activity and a decrease in the intensity of the 80
      100-kDa band, whereas the 57-kDa band decreases in size to yield a 47-kDa protein
      corresponding to the unglycosylated form of the transporter. Simultaneous
      mutation of Asn-169, Asn-172, Asn-182, and Asn-188 to Gln also produces the 47
      kDa form of the protein, indicating that there are no additional sites for N
      glycosylation. Progressive mutation of the potential glycosylation sites produces
      a progressive decrease in transport activity and in size of the protein,
      indicating that the four putative glycosylation sites are actually glycosylated.
      N-Glycosylation of the GLYT1 is not indispensable for the transport activity
      itself, as demonstrated by enzymatic deglycosylation of the transporter. Analysis
      of surface proteins by biotinylation and by immunofluorescence demonstrates that
      a significant portion of the unglycosylated GLYT1 mutant remains in the
      intracellular compartment. This suggests that the carbohydrate moiety of glycine
      transporter GLYT1 is necessary for the proper trafficking of the protein to the
      plasma membrane.

PMID- 7721870
TI  - In vitro expression of structural defects in the lecithin-cholesterol
      acyltransferase gene.
AB  - Classic LCAT deficiency (CLD) and fish eye disease (FED) are two clinically
      distinct syndromes, associated with defects in the lecithin-cholesterol
      acyltransferase (LCAT) gene resulting in total (CLD) or partial (FED) enzyme
      deficiency. In order to investigate the underlying molecular mechanisms that lead
      to different phenotypic expression in CLD and FED, LCAT mutants associated with
      either CLD (LCAT147, LCAT156, and LCAT228) or FED (LCAT10, LCAT123, LCAT158,
      LCAT293, LCAT300, and LCAT347) were expressed in vitro in human embryonic kidney
      293 cells and characterized with respect to LCAT expression and enzyme activity.
      Evaluation of mutant LCAT gene transcription by Northern blot analysis
      demonstrated LCAT mRNA of normal size and concentration. Although all constructs
      gave rise to similar intracellular LCAT mass, the amount of enzyme present in the
      media for LCAT147, LCAT156, and LCAT300 was reduced to less than 10% of normal,
      suggesting that these mutations disrupted LCAT secretion. Western blot analysis
      of cell culture media containing wild type or mutant LCAT demonstrated the
      presence of a single normal-sized band of 67 kDa. The ability of the different
      enzymes to esterify free cholesterol in high density lipoprotein-like
      proteoliposomes (alpha-LCAT-specific activity) was reduced to less than 5% of
      normal for CLD mutants LCAT147 and LCAT228 and FED mutants LCAT10, LCAT123,
      LCAT293, and LCAT347, whereas that of LCAT156, LCAT158, and LCAT300 ranged from
      45 to 110% of control. Although most FED mutant LCAT enzymes retained the ability
      to esterify free cholesterol present in alpha- and beta-lipoproteins of heat
      inactivated plasma, esterification was undetectable in all CLD mutants (LCAT147,
      LCAT156, and LCAT228). In contrast, all mutant enzymes retained the ability to
      hydrolyze the water soluble, short-chained fatty acid substrate p
      nitrophenolbutyrate. In summary, our studies establish the functional
      significance of nine LCAT gene defects associated with either FED or CLD.
      Characterization of the expressed LCAT mutants identified multiple, overlapping
      functional abnormalities that include defects in secretion and/or disruption of
      enzymic activity. All nine LCAT mutants retained the ability to hydrolyze the
      water-soluble PNPB substrate, indicating intact hydrolytic function. Based on
      these studies we propose that mutations in LCAT residues 147, 156, 228 (CLD) and
      10, 123, 158, 293, 300, and 347 (FED) do not disrupt the functional domain
      mediating LCAT phospholipase activity, but alter structural domains involved in
      lipid binding or transesterification.

PMID- 7721871
TI  - Mediation of growth hormone-dependent transcriptional activation by mammary gland
      factor/Stat 5.
AB  - Previous observations have shown that binding of growth hormone to its receptor
      leads to activation of transcription factors via a mechanism involving
      phosphorylation on tyrosine residues. In order to establish whether the prolactin
      activated transcription factor Stat 5 (mammary gland factor) is also activated by
      growth hormone, nuclear extracts were prepared from COS-7 cells transiently
      expressing transfected Stat 5 and growth hormone receptor cDNA. Gel
      electrophoresis mobility shift analyses revealed the growth hormone-dependent
      presence of specific DNA-binding proteins in these extracts. The complexes formed
      could be supershifted by polyclonal anti-Stat 5 antiserum. In other experiments
      nuclear extracts from growth hormone-treated Chinese hamster ovary cells stably
      expressing transfected growth hormone receptor cDNA and liver from growth hormone
      treated hypophysectomized rats were used for gel electrophoresis mobility shift
      analyses. These also revealed the presence of specific DNA-binding proteins
      sharing antigenic determinants with Stat 5. Stat 5 cDNA was shown to be capable
      of complementing the growth hormone-dependent activation of transcription of a
      reporter gene in the otherwise unresponsive COS-7 cell line. This complementation
      was dependent on the presence of Stat 5 tyrosine 694, suggesting a role for
      phosphorylation of this residue in growth hormone-dependent activation of DNA
      binding and transcription.

PMID- 7721872
TI  - Rapamycin selectively blocks interleukin-2-induced proliferating cell nuclear
      antigen gene expression in T lymphocyte. Evidence for inhibition of CREB/ATF
      binding activities.
AB  - The macrolide rapamycin arrests T lymphocytes stimulated by interleukin-2 (IL-2)
      at G1/S. We have recently found that IL-2 induced an increase in the binding of
      discrete transcription factors of the ATF/cAMP-responsive element binding factor
      (CREB) family at G1/S, and that this effect was inhibited by rapamycin
      (Feuerstein, N., Huang, D., Hinrichs, S. H., Orten, D. J., Aiyar, N., and
      Prystowsky, M. B. (1995) J. Immunol. 154, 68-79). We now show, by using high
      resolution two-dimensional gel electrophoresis, that rapamycin inhibited
      selectively the synthesis of three discrete IL-2-induced soluble proteins (35
      kDa/pI approximately 5, 68 kDa/pI approximately 4, 110 kDa/pI approximately 4.3).
      Analysis of nuclear proteins demonstrated that rapamycin selectively blocked the
      expression of proliferating cell nuclear antigen (PCNA), an obligate cofactor of
      DNA polymerase-delta, an important component for DNA replication. Rapamycin
      inhibited the IL-2-induced PCNA mRNA, and the murine PCNA promoter activity in IL
      2-stimulated cells. Inducible CRE-binding proteins were shown previously to be
      required for PCNA promoter activity in IL-2-stimulated T lymphocytes. Using DNA
      binding gel mobility shift assay we demonstrated that rapamycin potently
      inhibited the binding of CREB/ATF transcription factors to CRE elements in the
      murine proximal PCNA promoter. These results suggest that PCNA is a preferred
      target in a rapamycin-sensitive transduction pathway, and that the mechanism by
      which rampamycin inhibits PCNA gene expression may involve the inhibition of the
      interaction of CREB/ATF transcription factors with CRE elements in the proximal
      PCNA promoter.

PMID- 7721873
TI  - Binding interactions of human interleukin 5 with its receptor alpha subunit.
      Large scale production, structural, and functional studies of Drosophila
      expressed recombinant proteins.
AB  - Human interleukin 5 (hIL5) and soluble forms of its receptor alpha subunit were
      expressed in Drosophila cells and purified to homogeneity, allowing a detailed
      structural and functional analysis. B cell proliferation confirmed that the hIL5
      was biologically active. Deglycosylated hIL5 remained active, while similarly
      deglycosylated receptor alpha subunit lost activity. The crystal structure of the
      deglycosylated hIL5 was determined to 2.6-A resolution and found to be similar to
      that of the protein produced in Escherichia coli. Human IL5 was shown by
      analytical ultracentrifugation to form a 1:1 complex with the soluble domain of
      the hIL5 receptor alpha subunit (shIL5R alpha). Additionally, the relative
      abundance of ligand and receptor in the hIL5.shIL5R alpha complex was determined
      to be 1:1 by both titration calorimetry and SDS-polyacrylamide gel
      electrophoresis analysis of dissolved cocrystals of the complex. Titration
      microcalorimetry yielded equilibrium dissociation constants of 3.1 and 2.0 nM,
      respectively, for the binding of hIL5 to shIL5R alpha and to a chimeric form of
      the receptor containing shIL5R alpha fused to the immunoglobulin Fc domain
      (shIL5R alpha-Fc). Analysis of the binding thermodynamics of IL5 and its soluble
      receptor indicates that conformational changes are coupled to the binding
      reaction. Kinetic analysis using surface plasmon resonance yielded data
      consistent with the Kd values from calorimetry and also with the possibility of
      conformational isomerization in the interaction of hIL5 with the receptor alpha
      subunit. Using a radioligand binding assay, the affinity of hIL5 with full-length
      hIL5R alpha in Drosophila membranes was found to be 6 nM, in accord with the
      affinities measured for the soluble receptor forms. Hence, most of the binding
      energy of the alpha receptor is supplied by the soluble domain. Taken with other
      aspects of hIL5 structure and biological activity, the data obtained allow a
      prediction for how 1:1 stoichiometry and conformational change can lead to the
      formation of hIL5.receptor alpha beta complex and signal transduction.

PMID- 7721874
TI  - Identification of an inhibitor of tissue-type plasminogen activator-mediated
      fibrinolysis in human neutrophils. A role for defensin.
AB  - An inhibitor of tissue-type plasminogen activator (tPA)-mediated and plasminogen
      dependent fibrinolysis was isolated from human neutrophils. On a G-50 gel
      filtration column, the antifibrinolytic activity present in neutrophil
      homogenates comigrated with proteins of < 13 kDa. The inhibitory fraction had
      only a slight effect on urokinase with plasminogen- or plasmin-mediated
      fibrinolysis and no effect on urokinase- or plasmin-mediated cleavage of H-D
      valyl-L-leucyl-L-lysine-p-nitroanilide (S-2251). The neutrophil-derived fraction
      inhibited tPA with plasminogen activity on S-2251 but not on H-D-isoleucyl-L
      prolyl-L-arginine-p-nitroanilide (S-2288). The inhibition of tPA-mediated and
      plasminogen-dependent fibrinolysis or S-2251 cleavage showed a competitive
      pattern and could be relieved by increasing the concentration of plasminogen. The
      same fraction also inhibited binding of plasminogen to fibrin. Consecutive
      purification steps revealed that the molecular mass of the inhibitor was 1-5-kDa.
      Polylysine-Sepharose affinity chromatography indicated that the inhibitor is a
      protein of 4 kDa, migrating as one band on SDS-polyacrylamide gel
      electrophoresis. Amino acid sequence analysis of this band showed the presence of
      two sequences, differing by one amino acid, which are identical to defensin I and
      II. Comparison of the sequences of plasminogen and defensin showed homology of
      defensin to the plasminogen kringles known to contain the lysine binding sites.
      The close structural similarity between defensin and plasminogen kringles and the
      ability of defensin to compete with plasminogen on binding to fibrin explain the
      ability of defensin to inhibit tPA-mediated, plasminogen-dependent fibrinolysis.
      These results suggest that the antifibrinolytic activity of defensin may have a
      biological function in preventing the spread of infection.

PMID- 7721875
TI  - Alternative exon splicing within the amino-terminal nontriple-helical domain of
      the rat pro-alpha 1(XI) collagen chain generates multiple forms of the mRNA
      transcript which exhibit tissue-dependent variation.
AB  - Type XI collagen is an integral, although minor component of cartilage collagen
      fibrils. We have established that alternative exon usage is a mechanism for
      increasing structural diversity within the amino-terminal nontriple helical
      domain of the pro-alpha 1(XI) collagen gene. cDNA clones spanning the amino
      terminal domain were selected from a rat chondrosarcoma library, and were shown
      to contain two major sequence differences from the previously reported human
      sequence. The first difference was the replacement of sequence encoding an acidic
      domain of 39 amino acids in length by a sequence encoding a 51-amino acid basic
      domain with a predicted pI of 11.9. The second difference was the absence of a
      sequence that would translate into a highly acidic 85-amino acid sequence
      downstream from the first variation. These two changes, expressed together,
      result in the replacement of most of the acidic domain with one that is smaller
      and basic. These two sequence differences serve to identify subdomains of a
      variable region, designated V1 and V2, respectively. V1a is defined as the acidic
      39-amino acid sequence element and V1b is defined as the 51-amino acid basic
      sequence. Analysis of genomic DNA revealed that both V1a and V1b are encoded by
      separate adjacent exons in the rat genome and V2 is also encoded in a single exon
      downstream. Analysis of mRNA from cartilage-derived sources revealed a complex
      pattern of alpha 1(XI) transcript expression due to differential exon usage. In
      non-cartilage sources, the pattern is less complex; the most prevalent form is
      the one containing the two acidic sequences, V1a and V2.

PMID- 7721876
TI  - Alternative mRNA processing occurs in the variable region of the pro-alpha 1(XI)
      and pro-alpha 2(XI) collagen chains.
AB  - An analysis was performed of differential splicing of primary transcripts in the
      noncollagenous variable region located in the amino terminus of the pro-alpha
      1(XI) and pro-alpha 2(XI) collagen chains. The results for the pro-alpha 2(XI)
      chain showed that human cartilage or fibroblasts in culture contain transcripts
      in which a single highly acidic exon encoding for 21 amino acids is present or
      absent. For the chicken pro-alpha 1(XI) chain a more complex pattern of
      alternative splicing was detected with six possible variants. Of special interest
      was the alternative use of two exons (called IIA and IIB) in which IIA encodes
      for 39 amino acids and is highly acidic (estimated pI = 3.2), whereas IIB encodes
      for 49 amino acids and is highly basic (estimated pI = 10.6). A similar
      alternative use of exon IIA or exon IIB was also observed for human chondrocytes.
      Northern blotting with probes specific for IIA or IIB showed that both exons are
      present in transcripts from cartilage but exon IIB is preferentially utilized in
      transcripts from tendon. Present results suggest that both the pro-alpha 1(XI)
      and pro-alpha 2(XI) chains of type XI collagen undergo limited processing in vivo
      and that the noncollagenous variable region is initially retained on the surface
      of the fibrils. Differential splicing in the variable region may potentially
      influence the interaction of collagen fibrils with other molecules of the
      extracellular matrix and more specifically with sulfated glycosaminoglycan chains
      or with hyaluronan. Such interactions may play a key role in establishing both
      the organization of the collagen fibrils within the extracellular matrix and in
      limiting the diameter of collagen fibrils.

PMID- 7721877
TI  - Cellular nucleic acid binding protein regulates the CT element of the human c-myc
      protooncogene.
AB  - The CT element of the c-myc gene is required for promoter P1 usage and can drive
      expression of a heterologous promoter. Both double strand (Sp1) and single strand
      (hnRNP K) CT-binding proteins have been implicated as mediators of CT action.
      Although significant levels of CT activity persisted following Sp1
      immunodepletion, EGTA totally abolished transactivation, thus implicating another
      metal requiring factor in CT element activity. As hnRNP K binds to one strand of
      the CT element, but has no metal requirement, the opposite (purine-rich strand)
      was examined as a target for a metal-dependent protein. A zinc-requiring purine
      strand binding activity was identified as cellular nucleic acid binding protein
      (CNBP), a protein previously implicated in the regulation of sterol responsive
      genes. Two forms of CNBP differed in their relative binding to the CT- or sterol
      response elements. CNBP was shown to be a bona fide regulator of the CT element
      by cotransfection of a CNBP expression vector that stimulated expression of a CT
      driven but not an AP1-dependent reporter. These data suggest that hnRNP K and
      CNBP bind to opposite strands and co-regulate the CT element.

PMID- 7721878
TI  - Regulation of the adapter molecule Grb2 by the Fc epsilon R1 in the mast cell
      line RBL2H3.
AB  - Antigenic cross-linking of the high affinity IgE receptor (Fc epsilon R1) on mast
      cells results in protein tyrosine kinase activation. The object of the present
      study was to explore the regulation of the SH2 and SH3 domain containing adapter
      molecule Grb2 by Fc epsilon R1-stimulated PTK signal transduction pathways.
      Affinity purification of in vivo Grb2 complexes together with in vitro
      experiments with Grb2 glutathione S-transferase fusion proteins were used to
      analyze Grb2 complexes in the mast cell line RBL2H3. The data show that in RBL2H3
      cells several different proteins are complexed to the SH3 domains of Grb2. These
      include the p21ras guanine nucleotide exchange factor Sos, two basally tyrosine
      phosphorylated 110- and 120-kDa molecules, and a 75-kDa protein that is a
      substrate for Fc epsilon R1-activated PTKs. By analogy with Sos, p75, p110 and
      p120 are candidates for Grb2 effector proteins which suggests that Grb2 may be a
      pleiotropic adapter. Two Grb2 SH2-binding proteins were also characterized in
      RBL2H3 cells; the adapter Shc and a 33-kDa molecule. Shc is constitutively
      tyrosine phosphorylated in unstimulated cells and Fc epsilon R1 ligation induces
      no changes in its phosphorylation or binding to Grb2. In contrast, p33 is a
      substrate for Fc epsilon R1-activated PTKs and binds to Grb2 SH2 domains in Fc
      epsilon R1 activated but not quiescent cells. The beta subunit of the Fc epsilon
      R1 is a 33-kDa tyrosine phosphoprotein, but the p33 Grb2-binding protein
      described in the present report is not the Fc epsilon R1 beta chain and its
      identity is unknown. The present report thus demonstrates that there are multiple
      Grb2 containing protein complexes in mast cells of which a subset are Fc epsilon
      R1-regulated. Two other of the Grb2-binding proteins described herein are
      tyrosine phosphorylated in response to Fc epsilon R1 ligation: the 75-kDa protein
      which binds to Grb2 SH3 domains and the 33-kDa protein that associates with the
      Grb2 SH2 domain. We propose that protein complex formation by Grb2 is an
      important consequence of Fc epsilon R1 cross-linking and that this may be a
      signal transduction pathway which acts synergistically with calcium/PKC signals
      to bring about optimal mast cell end function.

PMID- 7721879
TI  - Dynamics of ubiquitin conjugation during erythroid differentiation in vitro.
AB  - To gain insight into the role of ubiquitin-mediated proteolysis in erythroid
      differentiation, levels of ubiquitin conjugating enzymes (E2s) and ubiquitin
      conjugates were analyzed during in vitro differentiation of murine
      erythroleukemic (MEL) cells. After 4 days of culture in the presence of the
      inducer dimethyl sulfoxide, MEL cells expressed high levels of the erythroid
      specific proteins, globin, and band 3. During the same interval, cellular
      contents (mol/cell) of E2-14K, E2-25K, and E2-35K decreased up to approximately 5
      fold; as suggested by results obtained with E2-25K, this reflected a lower level
      of mRNA in differentiating cells. Concentrations of these E2s changed more
      modestly during in vitro differentiation, since cellular volume also decreased.
      Comparison of levels of the three E2s in undifferentiated MEL cells and
      reticulocytes suggests that their concentrations remain fairly constant during in
      vivo differentiation of proerythroblasts into reticulocytes. Thus, these
      components of the ubiquitin-mediated proteolytic pathway are likely to function
      constitutively during this interval. Two-dimensional Western blots showed a broad
      spectrum of ubiquitin conjugates, including free multiubiquitin chains, in
      undifferentiated MEL cells. As seen for several E2s, the concentration of
      ubiquitin conjugates (including free chains) decreased modestly during in vitro
      differentiation. E2-20K and E2-230K, which are abundant in reticulocytes, were
      low or absent in undifferentiated and differentiated MEL cells. In erythroid
      cells these two E2s are reticulocyte-specific; apparently MEL cells do not
      differentiate far enough to allow induction of their expression.

PMID- 7721880
TI  - Proparathyroid hormone is preferentially cleaved to parathyroid hormone by the
      prohormone convertase furin. A mass spectrometric study.
AB  - Parathyroid hormone (PTH), an 84-amino acid peptide, is the major regulator of
      blood calcium homeostasis. Its mRNA, in addition to encoding the mature peptide,
      also encodes a "pre" sequence of 25 amino acids and a basic "pro" hexapeptide. To
      assess which of the subtilisin-like prohormone convertases can process proPTH to
      PTH we coinfected cells with a vaccinia virus construct expressing human
      preproPTH and vaccinia virus constructs expressing furin, PC1 or PC2. BSC-40
      cells, having a constitutive secretory pathway, and GH4C1 cells, having a
      regulated secretory pathway, were used. PTH biosynthetic products in cell
      extracts and media were purified by high performance liquid chromatography,
      identified by radioimmunoassay, and unambiguously defined as either proPTH or PTH
      by ion-spray mass spectrometry. In both cell types, furin was the most effective
      in processing proPTH to PTH. In all cases only PTH was released into the medium.
      In addition, partially purified furin and PC1 were tested for their ability to
      appropriately cleave a tridecapeptide spanning the prohormone cleavage site found
      in proPTH. Here too furin was much more effective at cleaving at the correct
      site. Northern blot analysis and in situ hybridization showed that furin and
      preproPTH mRNA are co-expressed in the parathyroid, whereas PC1, PC2, and PC5 are
      not and PACE4 is expressed only at very low levels. Taken together these studies
      strongly suggest that furin is the enzyme responsible for the physiological
      processing of proPTH to PTH.

PMID- 7721881
TI  - Generation of a mammalian cell line deficient in glucose-regulated protein stress
      induction through targeted ribozyme driven by a stress-inducible promoter.
AB  - GRP94 is an endoplasmic reticulum (ER) localized glycoprotein with Ca2+ binding
      and protein chaperoning properties. Using a ribozyme driven by a stress-inducible
      promoter and targeted against grp94 mRNA, we have generated a cell line deficient
      in its ability to induce GRP94. The effect of the ribozyme is mediated by the
      cleavage of the grp94 message just downstream of the initiation codon, and not by
      an antisense effect, as determined by the level of intact grp94 mRNA.
      Unexpectedly, this cell line's ability to induce GRP78 is also impaired.
      Transient overexpression of recombinant human lysosomal hydrolase alpha-L
      iduronidase in the ribozyme expressing cells indicates that the secretion ratio
      of this enzyme is reduced by about 6-fold. Additionally, the ribozyme expressing
      cells showed increased sensitivity to Ca2+ depletion from ER caused by either
      A23187 or thapsigargin, an ER-Ca(2+)-ATPase inhibitor, but not to tunicamycin.
      These combined results show that the induction of GRP94 may play important roles
      in ER to nuclear signaling, protein sorting and secretion, and specific
      protection against Ca2+ depletion stress.

PMID- 7721882
TI  - Characterization of the amino-terminal transcriptional activation function of the
      human estrogen receptor in animal and yeast cells.
AB  - We have previously reported that the transcriptional activation function AF-1,
      located in the A/B region of the human estrogen receptor, exhibits cell-type and
      promoter context specificity in both animal cells and yeast. To further
      characterize AF-1, we have constructed a number of deletion mutants spanning the
      A/B region in the context of either the whole human estrogen receptor or the A/B
      region linked to the GAL4 DNA binding domain, and tested their transcriptional
      activity in chicken embryo fibroblasts and in yeast cells, two cell types in
      which AF-1 efficiently activates transcription on its own. Additionally, we
      utilized HeLa cells in which AF-1 is poorly active but can synergize with the
      transcriptional activation function AF-2 located in the hormone binding domain.
      We show that in animal cells the "independent" activity of AF-1 is embodied in a
      rather hydrophobic proline-rich 99-amino acid activating domain (amino acids 51
      149), whereas amino acids 51-93 and 102-149 can independently synergize with AF
      2. Interestingly, in yeast, three discrete activating domains (amino acids 1-62,
      80-113, and 118-149) are almost as active on their own as the whole A/B region,
      indicating that multiple activating domains can operate independently in yeast.
      Our study also demonstrates that, within the context of the whole human estrogen
      receptor, the same AF-1 activating domains are "induced" by either estradiol or 4
      hydroxytamoxifen.

PMID- 7721883
TI  - Low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor
      mediates the cellular internalization and degradation of thrombospondin. A
      process facilitated by cell-surface proteoglycans.
AB  - Thrombospondin (TSP) is a cell and matrix glycoprotein that interacts with a
      variety of molecules. Newly synthesized thrombospondin is either incorporated
      into the extracellular matrix, or binds to the cell surface where it is rapidly
      internalized and degraded (McKeown-Longo, P. J., Hanning, R., and Mosher, D. F.
      (1984) J. Cell Biol. 98, 22-28). In the current investigation we identify the low
      density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP)
      as a receptor responsible for mediating the internalization of TSP leading to its
      degradation. LRP is a large cell surface receptor consisting of a 515-kDa heavy
      chain and an 85-kDa light chain proteolytically derived from a 600-kDa precursor.
      A specific and high affinity interaction between purified LRP and TSP was
      demonstrated by homologous ligand competition experiments, where a KD of 3-20 nM
      was measured using different preparations of TSP. The binding of TSP to purified
      LRP was completely inhibited by the 39-kDa receptor-associated protein, a known
      antagonist of ligand binding by LRP. Cultured fibroblasts rapidly internalize and
      degrade 125I-labeled TSP via a receptor-mediated process. This process is
      inhibited by receptor-associated protein and by antibodies against LRP,
      indicating that LRP is mediating the cellular internalization of TSP. Our studies
      also confirm that the efficient catabolism of TSP requires the participation of
      cell surface proteoglycans, since digestion of cells with heparitinase markedly
      reduces the extent of LRP-mediated TSP degradation. The ability of LRP to
      directly bind and mediate the cellular internalization and degradation of TSP
      indicates that this receptor may play an important role in the catabolism of TSP
      in vivo.

PMID- 7721884
TI  - Mutation of the cytoplasmic domain of the integrin beta 3 subunit. Differential
      effects on cell spreading, recruitment to adhesion plaques, endocytosis, and
      phagocytosis.
AB  - The cytoplasmic domain of the beta subunit of the alpha IIb beta 3 integrin is
      required for cell spreading on fibrinogen. Here we report that deletion of six
      amino acids from the COOH terminus of the beta 3 (I757TYRGT) totally abolished
      cell spreading and formation of adhesion plaques, whereas retaining Ile757
      partially preserved these functions. We further found that substitution of Tyr747
      with Ala also abolished alpha IIb beta a-mediated cell spreading. The effects of
      these and other mutations on additional functions of alpha IIb beta 3 were also
      studied. Progressive truncations of beta 3, in which stop codons were inserted at
      amino acid positions 759-756, caused partial defects in the recruitment of alpha
      IIb beta 3 to preestablished adhesion plaques and a gradual decrease in the
      ability of alpha IIb beta 3 to mediate internalization of fibrinogen-coated
      particles. The Tyr747-->Ala substitution mutant was almost totally inactive in
      both of these assays. Point mutations at Tyr759, and at a conserved area close to
      the transmembrane domain of beta 3, decreased integrin recruitment to
      preestablished adhesion plaques but allowed alpha IIb beta 3-mediated formation
      of these structures and partial cell spreading. Deletion of the cytoplasmic
      domain of beta 3 did not affect the constitutive endocytosis of alpha IIb beta 3.

PMID- 7721885
TI  - Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in
      human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different
      mechanisms.
AB  - Our previous studies in human monocytes have demonstrated that interleukin (IL)
      10 inhibits lipopolysaccharide (LPS)-stimulated production of inflammatory
      cytokines, IL-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha by
      blocking gene transcription. Using electrophoretic mobility shift assays (EMSA),
      we now show that, in monocytes stimulated with LPS or TNF alpha, IL-10 inhibits
      nuclear stimulation of nuclear factor kappa B (NF kappa B), a transcription
      factor involved in the expression of inflammatory cytokine genes. Several other
      transcription factors including NF-IL-6, AP-1, AP-2, GR, CREB, Oct-1, and Sp-1
      are not affected by IL-10. This selective inhibition by IL-10 of NF kappa B
      activation occurs rapidly and in a dose-dependent manner and correlates well with
      IL-10's cytokine synthesis inhibitory activity in terms of both kinetics and dose
      responsiveness. Furthermore, compounds such as tosylphenylalanyl chloromethyl
      ketone and pyrrolidinedithiocarbamate that are known to selectively inhibit NF
      kappa B activation block cytokine gene transcription in LPS-stimulated monocytes.
      Taken together, these results suggest that inhibition of NF kappa B activation
      may be an important mechanism for IL-10 suppression of cytokine gene
      transcription in human monocytes. IL-4, another cytokine that inhibits cytokine
      mRNA accumulation in monocytes, shows little inhibitory effect on LPS-induced NF
      kappa B activation. Further examination reveals that, unlike IL-10, IL-4 enhances
      mRNA degradation and does not suppress cytokine gene transcription. These data
      indicate that IL-10 and IL-4 inhibit cytokine production by different mechanisms.

PMID- 7721886
TI  - Aggregation of secreted amyloid beta-protein into sodium dodecyl sulfate-stable
      oligomers in cell culture.
AB  - Filamentous aggregates of the 40-42-residue amyloid beta-protein (A beta)
      accumulate progressively in the limbic and cerebral cortex in Alzheimer's
      disease, where they are intimately associated with neuronal and glial
      cytopathology. Attempts to model this cytotoxicity in vitro using synthetic
      peptides have shown that monomeric A beta is relatively inert, whereas aggregated
      A beta reproducibly exerts a variety of neurotoxic effects. The processes that
      mediate the conversion of monomeric A beta into a toxic aggregated state are thus
      of great interest. Previous studies of this conversion have employed high
      concentrations (10(-5)-10(-3) M) of synthetic A beta peptides under nonbiological
      conditions. We report here the detection of small amounts (< 10(-9) M) of SDS
      stable A beta oligomers in the culture media of Chinese hamster ovary cells
      expressing endogenous or transfected amyloid beta-protein precursor genes. The
      identity of these oligomers (primarily dimers and trimers) was established by
      immunoprecipitation with a panel of A beta antibodies, by electrophoretic
      comigration with synthetic A beta oligomers, and by amino acid sequencing. The
      oligomeric A beta species comprised approximately 10-20% of the total
      immunoprecipitable A beta in these cultures. A truncated A beta species beginning
      at Arg 5 was enriched in the oligomers, suggesting that amino-terminal
      heterogeneity can influence A beta oligomerization in this system. Addition of
      Congo red (10 microM) during metabolic labeling of the cells led to increased
      monomeric and decreased oligomeric A beta. The ability to detect and quantitate
      oligomers of secreted A beta peptides in cell culture should facilitate dynamic
      studies of the critical process of initial A beta aggregation under physiological
      conditions.

PMID- 7721887
TI  - Identification of three tyrosine residues of glycoprotein Ib alpha with distinct
      roles in von Willebrand factor and alpha-thrombin binding.
AB  - The interaction between von Willebrand factor (vWF) and the platelet membrane
      glycoprotein (GP) Ib-IX-V complex is essential for platelet adhesion at sites of
      vascular injury under high shear stress flow conditions. Moreover, GP Ib-IX-V may
      contribute to the mechanisms of platelet activation through its high affinity
      binding of alpha-thrombin. There are two distinct but partially overlapping
      regions of GP Ib alpha thought to be involved in interacting with vWF (residues
      251-279) and alpha-thrombin (residues 271-284); they share three tyrosine
      residues (positions 276, 278, and 279) that have recently been shown to be
      sulfated (Dong, J., Li, C. Q., and Lopez, J.A. (1994) Biochemistry 33, 13946
      13953). To define the functional role of these three residues, we have introduced
      selected mutations in a soluble recombinant GP Ib alpha fragment (corresponding
      to the sequence 1-302 of the mature protein) that binds vWF and alpha-thrombin
      with the same attributes as intact GP Ib-IX-V complex. Fragments containing a
      single Tyr-->Phe substitution either at position 276 or 278 or 279 exhibited
      normal interaction with vWF but markedly reduced or absent binding of alpha
      thrombin. GP Ib alpha fragment with normal sequence but synthesized under sulfate
      free conditions also failed to bind alpha-thrombin and, in addition, had markedly
      reduced interaction with vWF. The simultaneous substitution of three neighboring
      Asp residues with Asn at positions 272, 274, and 277, a multiple mutation that
      may impair Tyr sulfation, also resulted in loss of binding of both ligands. These
      results define distinct structural features of GP Ib alpha selectively involved
      in supporting the interaction with vWF or alpha-thrombin.

PMID- 7721888
TI  - Upstream organization of and multiple transcripts from the human folylpoly-gamma
      glutamate synthetase gene.
AB  - Folylpoly-gamma-glutamate synthetase (FPGS) is essential for the survival of
      proliferating mammalian cells and central to the action of all "classical" folate
      antimetabolites. We report the isolation of cDNAs corresponding to the 5' ends of
      FPGS mRNA from both human and hamster cells which include a start codon upstream
      of and in-frame with the AUG in the previously reported FPGS open reading frame.
      The predicted hamster and human amino-terminal extension peptides have features
      consistent with a mitochondrial targeting sequence. Ribonuclease protection and
      5'-rapid amplification of cDNA ends assays indicated multiple transcriptional
      start sites consistent with the sequence of the promoter region of this gene,
      which was highly GC-rich and did not contain TATA or CCAAT elements. These start
      sites would generate two classes of transcripts, one including the upstream AUG
      and one in which only the downstream AUG would be available for translation
      initiation. Transfection of the full length human cDNA into cells lacking FPGS
      restored their ability to grow in the absence of glycine, a product of
      mitochondrial folate metabolism, as well as of thymidine and purines. Therefore,
      we propose that the mitochondrial and cytosolic forms of FPGS are derived from
      the same gene, arising from the use of the two different translation initiation
      codons, and that the translation products differ by the presence of a 42-residue
      amino-terminal mitochondrial leader peptide.

PMID- 7721889
TI  - The structural basis for the specificity of epidermal growth factor and heregulin
      binding.
AB  - Heregulin is a ligand for the erbB3 and erbB4 receptors, with a region of high
      homology to epidermal growth factor (EGF). Despite this homology, these ligands
      bind to their corresponding receptors with great specificity. We report here the
      synthesis of heregulin beta 177-241 and show that a region consisting of amino
      acids 177-226 is sufficient both for binding and stimulation of receptor
      phosphorylation. Studies of chimeric EGF/heregulin peptides revealed that amino
      acids 177-181 of heregulin provide the specificity for binding to the heregulin
      receptor. The substitution of amino acids 177-181 of heregulin for the N terminus
      of EGF produced a unique bifunctional agonist that binds with high affinity to
      both the EGF receptor and the heregulin receptor.

PMID- 7721890
TI  - Midkine enhances fibrinolytic activity of bovine endothelial cells.
AB  - A hitherto unknown function of midkine (MK) was found in the regulation of
      fibrinolytic activity of vascular endothelial cells. Recombinant murine MK
      enhanced plasminogen activator (PA)/plasmin levels in bovine aortic endothelial
      cells (BAECs) in a dose- and time-dependent manner. After incubation with 10
      ng/ml MK for 18 h, PA and plasmin levels increased 6- and 4-fold, respectively.
      This effect was attributed to a moderate upregulation of urokinase-type PA
      expression as well as to a significant down-regulation of PA inhibitor-1 (PAI-1)
      expression. BAECs constitutively synthesized and secreted MK and its production
      was enhanced 2-fold with 1 microM retinoic acid or 10 microM retinol. It was
      found that MK served as a substrate for tissue transglutaminase. In the culture
      medium, MK existed as a transglutaminase-mediated complex of 36 kDa. Addition of
      anti-MK antibody to BAEC cultures resulted in a decrease of basal PA activity and
      an increase of basal PAI-1 levels and attenuated the ability of retinol to
      enhance PA activity 50% and potentiated the ability to increase PAI-1 levels 4
      fold. Furthermore, MK and basic fibroblast growth factor (bFGF) acted more than
      additively in enhancing PA levels. We conclude that in BAECs MK is a novel
      autocrine factor sustaining the fibrinolytic property. MK functions as a mediator
      of retinoid and cooperates with bFGF to enhance fibrinolytic activity of BAECs.

PMID- 7721891
TI  - Mimosine arrests DNA synthesis at replication forks by inhibiting
      deoxyribonucleotide metabolism.
AB  - Mimosine has been reported to specifically prevent initiation of DNA replication
      in the chromosomes of mammalian nuclei. To test this hypothesis, the effects of
      mimosine were examined in several DNA replication systems and compared with the
      effects of aphidicolin, a specific inhibitor of replicative DNA polymerases. Our
      results demonstrated that mimosine inhibits DNA synthesis in mitochondrial,
      nuclear, and simian virus 40 (SV40) genomes to a similar extent. Furthermore,
      mimosine and aphidicolin were indistinguishable in their ability to arrest SV40
      replication forks and mammalian nuclear chromosomal replication forks. In
      contrast to aphidicolin, mimosine did not inhibit DNA replication in lysates of
      mammalian cells supplied with exogenous deoxyribonucleotide triphosphate
      precursors for DNA synthesis. Mimosine also had no effect on initiation or
      elongation of DNA replication in Xenopus eggs or egg extracts containing high
      levels of deoxyribonucleotide triphosphates. In parallel with its inhibitory
      effect on DNA synthesis in mammalian cells, mimosine altered deoxyribonucleotide
      triphosphate pools in a manner similar to that reported for another DNA
      replication inhibitor that affects deoxyribonucleotide metabolism, hydroxyurea.
      Taken together, these results show that mimosine inhibits DNA synthesis at the
      level of elongation of nascent chains by altering deoxyribonucleotide metabolism.

PMID- 7721892
TI  - Amplification of a circular episome carrying an inverted repeat of the DFR1 locus
      and adjacent autonomously replicating sequence element of Saccharomyces
      cerevisiae.
AB  - Lack of suitable amplification markers has hindered the use of the yeast system
      for investigating the mechanism of gene amplification in a eukaryote with a
      simple genome and well defined genetic system. Recently, methotrexate has been
      used to select for Saccharomyces cerevisiae mutants with de novo amplification of
      the dihydrofolate reductase gene (DFR1) (Huang, T. (1993) In Vivo Disruption and
      de Novo Amplification of the DFR1 Gene Encoding Dihydrofolate Reductase in
      Saccharomyces cerevisiae. Ph. D. thesis, University of Alberta, Edmonton,
      Canada). We report here the detailed structure of a DFR1 episome amplified in
      methotrexate-resistant strain 25-1. The extrachromosomal DNA is found
      predominantly as a single 11-kilobase circular molecule. It consists of a 5.5
      kilobase inverted duplication that contains the DFR1 locus and adjacent ARS
      (autonomously replicating sequence) element. This molecular configuration mimics
      the inferred structure of double minute chromosomes observed in a number of
      mammalian amplification systems and suggests that mechanisms that generate
      amplified DNAs are conserved from yeast to mammals.

PMID- 7721893
TI  - Granulocyte macrophage-colony stimulating factor-dependent replication of polyoma
      virus replicon in hematopoietic cells. Analyses of receptor signals for
      replication and transcription.
AB  - Granulocyte macrophage-colony stimulating factor (GM-CSF) stimulates
      proliferation of various hematopoietic cells. Using cytoplasmic deletion mutants
      of the human GM-CSF receptor (hGMR) beta subunit and tyrosine kinase inhibitors,
      we previously showed that distinct signaling pathways of hGMR are involved in the
      induction of c-fos/c-jun mRNAs and of c-myc mRNA/cell proliferation. We used
      polyoma virus (Py) replicon to analyze the initiation of DNA replication induced
      by hGM-CSF in mouse BA/F3 pro-B cells expressing hGMR. hGM-CSF efficiently
      stimulated Py replication in the presence of Py enhancer and Py large T antigen
      supplied in trans. Analyses of Py enhancer mutants revealed that hGM-CSF promoted
      Py replication and activated transcription of the Py early promoter through the
      PEA3/PEBP5 region of Py enhancer. The membrane proximal region of hGMR beta
      subunit is required for activation of PEA3/PEBP5-dependent replication which is
      also required for activation of DNA synthesis in the host cells. In contrast, a
      more distal region which is essential for activation of c-fos and c-jun genes is
      required for the PEA3/PEBP5-dependent transcription of Py early promoter. These
      results indicate that distinct signaling pathways of hGMR are required to
      activate PEA3/PEBP5-dependent replication and transcription although the same
      enhancer is required for both activities.

PMID- 7721894
TI  - Tissue-specific expression of the gene for type I procollagen (COL1A1) in
      transgenic mice. Only 476 base pairs of the promoter are required if collagen
      genes are used as reporters.
AB  - Inconsistent data have been reported on the size of the promoter that is
      necessary for high levels of tissue-specific expression of the COL1A1 gene for
      type I procollagen. Some of the inconsistencies may be traced to the use of
      reporter gene constructs. Therefore, we prepared transgenic mice with
      modifications of the intact gene engineered so that the level of expression of
      the transgene could be assayed both as mRNA and protein that were similar to the
      products from the endogenous COL1A1 gene. The results with a mini-COL1A1 gene
      lacking 41 internal exons and introns indicated that the first intron and 90% of
      the 3'-untranslated region were not essential for tissue-specific expression. In
      a hybrid COL1A1/COL2A1 construct, a 1.9-kilobase 5'-fragment from the COL1A1 gene
      that contained only 476 of the promoter was linked to a promoterless 29.5
      kilobase fragment of the human COL2A1 gene for type II procollagen. The hybrid
      COL1A1/COL2A1 construct was expressed as both mRNA and protein in tissues that
      normally synthesize type I procollagen but not type II procollagen. Apparently,
      476 base pairs of the promoter are sufficient to drive tissue-specific expression
      of the COL1A1 gene and totally inappropriate expression of the COL2A1 gene.

PMID- 7721895
TI  - Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4) stimulated
      proliferation and requires a membrane-proximal region of IL4 receptor alpha.
AB  - The tyrosine kinases JAK1 and JAK3 have been shown to undergo tyrosine
      phosphorylation in response to interleukin-2 (IL), IL4, IL7, and IL9, cytokines
      which share the common IL2 receptor gamma-chain (IL2R gamma), and evidence has
      been found for a preferential coupling of JAK3 to IL2R gamma and JAK1 to IL2R
      beta. Here we show, using human premyeloid TF-1 cells, that IL4 stimulates JAK3
      to a larger extent than JAK1, based upon three different evaluation criteria.
      These include a more vigorous tyrosine phosphorylation of JAK3 as measured by
      anti-phosphotyrosine immunoblotting, a more marked activation of JAK3 as
      determined by in vitro tyrosine kinase assays and a more manifest presence of
      JAK3 in activated IL4-receptor complexes. These observations suggest that IL4
      receptor signal transduction does not depend on equimolar heterodimerization of
      JAK1 and JAK3 following IL4-induced heterodimerization of IL4R alpha and IL2R
      gamma. Indeed, when human IL4R alpha was stably expressed in mouse BA/F3 cells,
      robust IL4-induced proliferation and JAK3 activation occurred without detectable
      involvement of JAK1, JAK2, or TYK2. The present study suggests that JAK1 plays a
      subordinate role in IL4 receptor signaling, and that in certain cells exclusive
      JAK3 activation may mediate IL4-induced cell growth. Moreover, mutational
      analysis of human IL4R alpha showed that a membrane-proximal cytoplasmic region
      was critical for JAK3 activation, while the I4R motif was not, which is
      compatible with a role of JAK3 upstream of the recruitment of the insulin
      receptor substrate-1/4PS signaling proteins by IL4 receptors.

PMID- 7721896
TI  - Determination of the structural requirements for palmitoylation of p63.
AB  - Palmitoylation of p63, a type II membrane protein localized in the endoplasmic
      reticulum, is induced in a reversible manner by the drug brefeldin A. To study
      the requirements for palmitoylation, mutant forms of p63 were expressed in COS
      cells and analyzed by metabolic labeling with [3H]palmitate, immunoprecipitation,
      and SDS-polyacrylamide gel electrophoresis. By investigating deletion and point
      mutations, Cys100 in the 106-amino acid cytoplasmic tail of p63 has been
      identified as the site of acylation. Site-directed mutagenesis of residues 99-105
      together with cytoplasmic tail truncation mutants showed that the amino acids
      surrounding Cys100 are not critical for palmitoylation of this residue. Analysis
      of a chimeric construct between p63 and the plasma membrane protein
      dipeptidylpeptidase IV further revealed that p63 palmitoylation is not dependent
      on its transmembrane domain. In contrast, the six-amino acid distance between the
      end of the predicted transmembrane domain and the palmitoylation site was found
      to be essential for proper acylation of p63.

PMID- 7721897
TI  - Stimulation of DNA transcription by the replication factor from the adenovirus
      genome in a chromatin-like structure.
AB  - Adenovirus (Ad) genome DNA is complexed with viral core proteins in the virus
      particle and in host cells during the early stages of infection. This DNA protein
      complex, called Ad core, is thought to be the template for transcription and DNA
      replication in infected cells. The Ad core functioned as template for DNA
      replication in the cell-free system consisting of viral replication proteins,
      uninfected HeLa nuclear extracts, and a novel factor, template activating factor
      I (TAF-I) that we have isolated from uninfected HeLa cytoplasmic fractions. The
      Ad core did not function as an efficient template in the cell-free transcription
      system with nuclear extracts of uninfected HeLa cells. The addition of TAF-I
      resulted in the stimulation of transcription from E1A and ML promoters on the Ad
      core. TAF-I was required, at least, for the formation of preinitiation complexes.
      These observations suggest that, in addition to factors essential for
      transcription on naked DNA template, the factor such as TAF-I needed for
      replication of the Ad core is also required for transcription from the Ad genome
      in a chromatin-like structure.

PMID- 7721898
TI  - A mutant strain of Chlamydomonas reinhardtii lacking the chloroplast photosystem
      II psbI gene grows photoautotrophically.
AB  - The product of the chloroplast psbI gene is associated with the photosystem II
      reaction center. To gain insights into the function of this polypeptide, we have
      disrupted its gene in Chlamydomonas reinhardtii with an aadA expression cassette
      that confers resistance to spectinomycin through biolistic transformation. The
      transformants are still able to grow photoautotrophically in dim light, but not
      in high light, and they remain photosensitive when grown on acetate containing
      medium. The amounts of photosystem II complex and oxygen evolving activity are
      both reduced to 10-20% of wild-type levels in these psbI-deficient mutants. It
      appears that the PsbI polypeptide plays a role in the stability of photosystem II
      and possibly also in modulating electron transport or energy transfer in this
      complex.

PMID- 7721899
TI  - The cyclic AMP response element in the calcitonin/calcitonin gene-related peptide
      gene promoter is necessary but not sufficient for its activation by nerve growth
      factor.
AB  - The gene encoding calcitonin gene-related peptide (CGRP) is inducible by nerve
      growth factor (NGF) in primary dorsal root ganglion neurons. By transfecting
      these primary neurons, we have defined a region of the CGRP promoter from -140 to
      -72 relative to the transcriptional start site which is essential for its
      inducibility by NGF as well as by cyclic AMP and which can confer these responses
      on a heterologous promoter. A cyclic AMP response element (CRE) within this
      region is essential for both these responses which are abolished by site-directed
      mutagenesis of this element. In contrast to the intact fragment the isolated CRE
      can confer responsiveness to cyclic AMP but not NGF on a heterologous promoter.
      The reasons for the different role of the CRE in the response of the CGRP
      promoter to cyclic AMP and NGF are discussed.

PMID- 7721900
TI  - Multiple promoters in rat acyl-CoA synthetase gene mediate differential
      expression of multiple transcripts with 5'-end heterogeneity.
AB  - Nucleotide sequence analysis of six independently isolated cDNAs for rat acyl-CoA
      synthetase (ACS) revealed three forms of ACS mRNA, designated form-A, -B, and -C
      mRNAs, which differ in their 5'-untranslated regions. Form-A mRNA was
      preferentially detected in normal and peroxisome-induced livers, whereas form-B
      mRNA was found in peroxisome-induced livers but not in normal livers and hearts,
      and form-C mRNA was preferentially found in normal hearts and peroxisome-induced
      livers. Analysis of two overlapping genomic clones for the rat ACS gene revealed
      that the three 5'-untranslated regions of the mRNAs are individually encoded by
      three different exons located within a 20-kilobase genomic fragment. The
      transcription start sites of the three forms of ACS mRNA were determined and
      nucleotide sequences of 5'-upstream regions of the three 5'-end exons were
      determined. The 5'-upstream regions were fused to the chloramphenicol
      acetyltransferase gene and transcription units of the three forms of ACS mRNAs
      were determined. These data indicate that the three forms of ACS mRNA with 5'-end
      heterogeneity are generated by alternative transcription from three promoters in
      the rat ACS gene.

PMID- 7721901
TI  - Purification and characterization of DNA ligase III from bovine testes. Homology
      with DNA ligase II and vaccinia DNA ligase.
AB  - Mammalian cell nuclei contain three biochemically distinct DNA ligases. In the
      present study we have found high levels of DNA ligase I and DNA ligase III
      activity in bovine testes and have purified DNA ligase III to near homogeneity.
      The high level of DNA ligase III suggests a role for this enzyme in meiotic
      recombination. In assays measuring the fidelity of DNA joining, we detected no
      significant differences between DNA ligases II and III, whereas DNA ligase I was
      clearly a more faithful enzyme and was particularly sensitive to 3' mismatches.
      Amino acid sequences of peptides derived from DNA ligase III demonstrated that
      this enzyme, like DNA ligase II, is highly homologous with vaccinia DNA ligase.
      The absence of unambiguous differences between homologous peptides from DNA
      ligases II and III (10 pairs of peptides, 136 identical amino acids) indicates
      that these enzymes are either derived from a common precursor polypeptide or are
      encoded from the same gene by alternative splicing. Based on similarities in
      amino acid sequence and biochemical properties, we suggest that DNA ligases II
      and III, Drosophila DNA ligase II, and the DNA ligases encoded by the pox viruses
      constitute a distinct family of DNA ligases that perform specific roles in DNA
      repair and genetic recombination.

PMID- 7721902
TI  - Chronic pathophysiologic elevation of corticosterone after thermal injury or
      thermal injury and burn wound infection adversely affects body mass, lymphocyte
      numbers, and outcome.
AB  - The purpose of the present studies was to investigate the effect of
      glucocorticoids on catabolism and lymphocyte numbers in a rat model of thermal
      injury or thermal injury plus burn wound infection. Thermal injury alone caused
      only an acute increase in plasma corticosterone concentrations. Furthermore, body
      weight declined moderately (5%), and lymphocyte numbers in lymph nodes draining
      the burn wound and blood increased markedly, whereas splenic lymphocyte numbers
      declined by about 60%. By contrast uninjured rats subjected to chronic elevation
      of corticosterone by corticosterone pellet implantation showed large decreases in
      body weight and lymphocyte numbers in all tissues examined. The combination of
      injury and chronic corticosterone elevation resulted in body weight and
      lymphocyte changes intermediate between injury alone and corticosterone treatment
      alone. Chronic elevation of corticosterone for 4 days before burn wound infection
      significantly decreased survival time and survival. Burn wound infection
      immediately after injury caused chronic elevation of endogenous plasma
      corticosterone and body weight and numeric lymphocyte changes that were
      remarkably similar to those of uninjured rats treated with corticosterone.
      Finally, the glucocorticoid receptor antagonist RU 486 significantly increased
      survival time in thermally injured, burn wound-infected rats. These results lend
      support to a hypothesis that chronic elevation of plasma cortisol concentrations
      as observed in patients with burns may be deleterious.

PMID- 7721903
TI  - Plasma copper and iron changes in sheep after left lung inhalation injury: effect
      of the thromboxane antagonist BM 13.177 (Solutroban).
AB  - A significant decline in plasma concentrations of copper and iron were observed
      in sheep exposed to preferential smoke inhalation of the left lung. The decline
      was evident 30 minutes after smoke inhalation, and the levels of both trace
      metals persisted at quite low levels for up to the 18-hour time interval after
      injury. From that time a gradual recover for copper but not for iron levels was
      observed so that by 24 hours the levels of copper were in the same range of those
      at baseline. Copper and iron levels showed an inverse correlation to airway peak
      and plateau pressures and left lung vascular resistance index and a direct
      correlation to left lung blood flow. Administration of BM 13.177 (Solutroban), a
      thromboxane antagonist, before exposure to smoke inhalation protected the sheep
      from the decline of copper and iron levels in plasma. In these animals airway
      peak and plateau pressure, left lung vascular resistance, and blood flow were
      also unmodified. Lipid peroxidation of the lung tissue by oxygen free radicals
      were lower than in those animals that did not receive BM 13.177. There was
      likewise a tendency of a decreased wet-to-dry weight ratios in the animals
      treated with BM 13.177. BM 13.177 treatment in an inhalation injury model might
      partly protect lung damage and parallels unchanged plasma copper and iron levels.
      The plasma copper and iron may therefore be an indicator of acute lung damage.

PMID- 7721904
TI  - Endothelin levels in patients with burns covering more than 20% body surface
      area.
AB  - Endothelin is a peptide with 21 amino acids that is produced by ischemic or
      injured endothelial cells. As indicated by in vitro and animal studies,
      endothelin is also a potent constrictor for renal mesangial and coronary vessels,
      a bronchoconstrictor, and an endocrine regulator. Our laboratory has shown that
      endothelin is an agonist for monocyte production of interleukins-1, -6, and -8,
      prostaglandin E2, and substances that trigger superoxide production. Systemic
      endothelin levels increase in patients with hypoperfusion and sepsis, indicating
      that endothelin may be yet another important cytokine in critical illness. Though
      endothelin has been shown to be a potent vasoconstrictor in healthy dogs,
      systemic vascular resistance does not increase in critically ill patients with
      high endothelin levels. (We hypothesize that this might be due to prostaglandin
      E2-mediated vasodilation predominating over endothelin-mediated
      vasoconstriction.) We questioned whether any changes occur in systemic endothelin
      levels in patients with major burns (> 20%). Ten hemodynamically stable patients
      resuscitated by a modified Parkland formula to a urine output greater than 30
      ml/hr had endothelin levels drawn on admission and at 1, 6, 12, 24, and 48 hours
      after admission. Endothelin levels were measured by radioimmunoassay. Mean
      endothelin levels were elevated at 205 +/- 28 fmol/ml at all time points in
      contrast to levels of 39 +/- 9 fmol/ml in the healthy control group. In summary,
      systemic endothelin levels increase significantly in patients with major burns.
      Endothelin may be yet another cytokine playing a significant role in the immune,
      inflammatory, and multiorgan dysfunction observed with major burns.

PMID- 7721905
TI  - An experimental study to determine the effects of Dermagraft on skin graft
      viability in the presence of bacterial wound contamination.
AB  - Dermagrafts (Advanced Tissue Science, La Jolla, Calif.) is a possible dermal
      substitute currently in early stages of clinical trials. It consists of
      polyglycolic acid mesh impregnated with viable, human, neonatal fibroblasts. The
      randomized prospective study with the mouse model was undertaken to determine the
      effect of Dermagraft on skin graft viability in the presence of wound
      contamination with controlled concentrations of commonly encountered burn wound
      pathogens. Appropriate controlled series were run concurrently. Placement of
      Dermagraft, or polyglycolic acid mesh, had no significant effect on skin graft
      viability when compared with simple skin grafts. Controlled bacterial
      contamination of skin grafts with Dermagraft did not significantly change the
      occurrence of graft viability when compared with control groups of skin grafts
      with controlled bacterial contamination. These studies suggest that Dermagraft
      does not increase the occurrence of graft loss in the face of wound bed
      contamination.

PMID- 7721906
TI  - Micrografts. II: Evaluation of 25:1, 50:1, and 100:1 expansion skin grafts in the
      porcine model.
AB  - This study was undertaken to evaluate 25:1, 50:1, and 100:1 expansions of
      micronized skin grafts in a porcine model. Two full-thickness skin excisions
      (graft and control) were performed on each of 30 immature pigs (20 pounds). The
      pigs were divided into three groups of 10 animals each: group A, 25 cm2; group B,
      50 cm2; and group C, 100 cm2. One square centimeter of the excised skin was
      thinned to produce a thick split-thickness skin graft. Four 90-degree passes were
      made through a skin mesher with the smooth side of the plastic mesh carrier to
      produce uniform pieces of skin. These pieces were applied to one area on each
      pig. Both the graft and control sites were covered with film. The film was
      removed on postoperative day 7, and excision sites were photographed on
      postoperative days 7, 10, 14, and 21. Healing was evaluated with a 12 x 12 inch
      digitizing pad to estimate the percent area healed. Healing was compared via
      analysis of variance, with percent area healed used as the dependent variable and
      treatment (control or graft) and postoperative day and expansion size used as the
      independent variables. No difference was found on postoperative day 7. On
      postoperative day 10, 25:1 grafts healed better than the 50:1 grafts, which were
      healed more than the 100:1 grafts. No difference was seen between 25:1 and 50:1
      grafts on postoperative day 14; however, they were healed better than the 100:1
      expansion grafts. No difference was seen between the graft sites on postoperative
      day 21.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721907
TI  - Treatment of fourth-degree hand burns.
AB  - Fourth-degree hand burns are rare but devastating injuries. They cannot be
      grafted readily but often require flaps and amputation, and impairment is
      significant. We report our 10-year experience (1981 to 1990) with deep hand burns
      to characterize our treatment and outcome. A total of 25 patients (35 hands) were
      treated. Eight local flaps, nine distant flaps, and two free-tissue transfers
      were performed. Eleven hands were treated with K-wire immobilization and
      grafting. Thirty-three amputations were done. Postburn function was evaluated in
      25 salvaged hands. Eleven hands had good outcomes, whereas seven had moderate
      sequelae and seven were severely affected. Patients who were treated with flap
      coverage of exposed tendons and joints had better functional outcomes than those
      treated with delayed closure with immobilization and grafting. The excellent
      outcomes in the flap coverage group justifies the added commitment of technical
      and therapeutic resources that this treatment requires.

PMID- 7721908
TI  - An eleven-year survey of electrical burn injuries.
AB  - One hundred eighty-six patients with electrical burns were treated within an 11
      year period at The Hacettepe University Burn Unit. Both children and adults were
      treated in this burn unit. The main causes of injury were misuse of electrical
      appliances, inattentiveness, lack of education in safety precautions, and lack of
      parental supervision. Treatment consisted of first, normal resuscitation in which
      Ringer's lactate solution was administered (according to the Parkland formula).
      Fluid resuscitation was followed by debridement, fasciotomy, and escharatomy. Two
      major complications were encountered: musculoskeletal involvement in 44% of
      patients, which required major amputation in 79%, and acute renal failure in
      14.51% of patients. In spite of treatment with peritoneal dialysis or
      hemodialysis, the mortality rate for patients with renal failure was quite high
      (59%). To decrease the number of complications, closer monitoring of patients and
      early surgical decompression were applied. The results of this survey demonstrate
      the need for burn prevention programs in Turkey. Physicians and health care
      officials have an obligation to educate the public about the prevention of
      electrical burns. The results of this study and other studies on electrical burns
      should be communicated to the public through every available means.

PMID- 7721909
TI  - Phosphorous burns: evaluation of various modalities for primary treatment.
AB  - White phosphorus is used in many types of military munitions, in fireworks, and
      in industrial and agricultural products. It ignites spontaneously and causes deep
      thermal injuries. It may also cause multiorgan failure because of its toxic
      effects on erythrocytes, liver, kidneys, and heart. Our previous studies
      demonstrated deleterious effects of copper sulfate. Only copious water irrigation
      was effective. This study examined other modalities of treatment and a free
      oxygen radical scavenger. One of the treatments seemed to have some beneficial
      effects, but simple water irrigation was much more effective. Superoxide
      dismutase, a free radical scavenger, reduced hepatic damage and adjacent skin
      flap destruction but did not prevent death of the animal receiving the high dose
      of white phosphorus used in the present setup.

PMID- 7721910
TI  - A retrospective review of the burn intensive care unit admissions for a year.
AB  - One hundred twenty-three patients who were admitted to the University of Florida
      burn intensive care unit during a 1-year period were included in this
      retrospective study. The average age of the patients was 28 years (range 3 months
      to 90 years), and the average size of the total body surface area burned was 18%,
      with 7% full-thickness burns. The average hospital stay of each patient was 17.46
      days. One hundred twelve operations were carried out in the burn unit's operating
      room with a circulating nurse from the registered nursing staff of the burn
      intensive care unit. No major complications occurred during the procedures. There
      were 1689 hydrotherapies and 2496 splint days. No significant loss of function of
      the patients' extremities developed while the patients were in the burn intensive
      care unit after the 112 debridement and skin grafting procedures were done.
      During the year, 365 follow-up examinations were done on previously discharged
      patients in the outpatient clinic area of the burn intensive care unit, which
      gave the doctors, registered nurses, and therapists an opportunity to determine
      their patients' progress. During the past year 537 separate pieces of compression
      garments were fitted.

PMID- 7721911
TI  - Evaluation of calcium alginate for skin graft donor sites.
AB  - Choosing the most appropriate wound dressing is of importance in optimizing
      healing and minimizing pain. Recent reports have suggested an improvement in
      wound healing with calcium alginate. To clinically evaluate this new dressing, 12
      paired wounds were covered with either calcium alginate or scarlet red in seven
      patients with burns undergoing skin grafting. The rate of reepithelialization was
      assessed by optical planimetry for the calcium alginate and by time for sloughing
      of the scarlet red. This comparison failed to demonstrate objectively any
      difference in the rate of wound healing between these dressings; however, calcium
      alginate did significantly reduce the pain severity and was favored by the
      nursing personnel because of its ease of care. Thus calcium alginate does appear
      to have clinical advantages as a dressing for skin graft donor sites.

PMID- 7721912
TI  - The burn unit as a resource for the management of acute nonburn conditions in
      children.
AB  - Burn units bring together resources to manage large complex wounds, organ
      failures, and the hypermetabolic response to injury. These resources can also
      facilitate management of other problems such as purpura fulminans, toxic
      epidermal necrolysis, staphylococcal scalded skin syndrome, and major mechanical
      soft-tissue injuries. During a recent 10-year interval 2.4% of all acute
      admissions to a regional pediatric burn facility were in this category and form
      the basis for this review.

PMID- 7721913
TI  - Innovations in the design and performance of underpads for patients with burns.
AB  - The purpose of this study was to determine the biomechanical performance of
      commercially available underpads and bed linens to reduce the development of
      pressure sores in patients with burns who are at high risk. The three
      biomechanical performance parameters examined were coefficient of friction,
      absorbent capacity, and rewet. Because wetting either cotton or cotton/polyester
      bedsheets markedly increases their coefficients of friction, underpads should be
      used routinely to protect the skin against frictional forces. One disposable
      underpad is ideally suited to protect the skin of the patient at high risk. It
      has a polyolefin backing with a low coefficient of friction that serves as an
      effective barrier to moisture transmission while still shifting easily with the
      patient's movement. In addition, it is the only underpad studied that contains a
      superabsorbent polymer that provides a far superior absorbent capacity and
      minimizes rewet. Wet-back is further inhibited by its thick intermediate tissue
      layer and its spunbonded polypropylene coverstock.

PMID- 7721914
TI  - Evaluation of a vertical mouth stretching orthosis: two case reports.
AB  - Burns around the mouth frequently result in contractures or microstomia. Orthoses
      used in the past have usually been designed to stretch the mouth horizontally.
      Finding a comfortable effective way to stretch the mouth vertically proved to be
      a challenge. A jaw positioner was used for vertical mouth stretching in two case
      studies and was evaluated for effectiveness of preventing mouth contractures and
      for comfort, durability, ease of use, adaptability for children, and ease of
      measuring results. Vertical and horizontal passive range of motion increased with
      initial use and then was maintained in both patients. The jaw positioner was
      comfortable and easy to use. This orthosis could be adapted to fit in a child's
      mouth and was impossible to swallow. Progress was easy to monitor with the
      numeric scale on the orthosis. Though no single orthosis will be ideal for every
      oral burn, this jaw positioner is recommended for pediatric and adult patients
      with extensive circumoral burns who demonstrate fair to good compliance.

PMID- 7721915
TI  - Burn physician reimbursement policy.

PMID- 7721916
TI  - Regional and institutional variation in burn care.
AB  - In reviewing the literature on burn therapy and observing clinical burn care, we
      noted differences among institutions and individual experts in several areas. To
      study variation in burn care, we surveyed the 140 burn centers listed by the
      American Burn Association to determine how burn care is currently administered in
      the United States and Canada. Responses were obtained from 83 hospitals (60%).
      The survey addressed resuscitation, operative and nonoperative wound care,
      medications, antimicrobial agents, and pain control. The major influence on care
      appeared to be the experience of the director (considered "very influential" in
      85%) compared with the literature ("very influential" in 12%) and habit/what
      works for us ("very influential" in 48%). The Parkland formula was used "always"
      or "often" by 78%, and the Brooke formula "never" by 81% of respondents. Lactated
      Ringer's solution was the most popular initial fluid, and most (78%) respondents
      changed fluids after 24 hours. However, the fluids used in the second 24 hours
      varied equally among several choices. The use of colloids also varied without a
      set pattern. Furosemide (Lasix) and nonsteroidal antiinflammatory drugs were used
      "rarely" or "never" by 67% of centers in the acute stage. H2 blockers were used
      for gastritis prophylaxis "always" or "often" in 60% (vs 53% for antacids and 20%
      for sucralfate [Carafate]). Tube feedings were started on day 1 after burn injury
      "always" by less than 30% of centers. Total parenteral nutrition was not commonly
      used. Most centers use of silver sulfadiazine on the body and hands, but facial
      topical antimicrobial therapy varied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721917
TI  - An effective method of educating junior high-aged children in fire and burn
      safety without disruption of the school curriculum.
AB  - A 2-hour educational seminar focusing on fire and burn safety issues was
      developed, presented, and evaluated by the fire department. The eighth-grade
      class at a local junior high school was selected for the pilot site for the
      seminar. A pretest and posttest were developed to measure the informational gain
      and retention of learned material to the students. Test results showed a
      statistically significant improvement in burn and fire safety scores of the
      tested children.

PMID- 7721918
TI  - The burn team functions as a unit to help the patient survive, recover, and
      rehabilitate.

PMID- 7721919
TI  - The use of APACHE III to evaluate ICU length of stay, resource use, and mortality
      after coronary artery by-pass surgery.
AB  - OBJECTIVE: To identify patient characteristics that are associated with increased
      ICU length of stay, resource use, and hospital mortality after coronary artery
      bypass surgery. DESIGN: Prospective, multicenter study. SETTING: Six tertiary
      care hospitals. PARTICIPANTS: A consecutive sample of 2,435 unselected ICU
      admissions following coronary artery by-pass surgery. MATERIALS AND METHODS:
      Demographic, operative characteristics and APACHE III score were collected during
      the first postoperative day; and APACHE III scores and therapeutic interventions
      during the first three postoperative days. Hospital survival and ICU length of
      stay were also recorded. Multivariate equations were derived and cross-validated
      to predict hospital mortality, ICU length of stay, and ICU resource use. RESULTS:
      Unadjusted hospital mortality rate was 3.9% (range 1.0% to 6.0%), mean ICU length
      of stay was 3.7 days (range 3.2 to 4.7 days), and first 3-day ICU resource use
      (TISS points) was 99 (range 68 to 116). The range of actual to predicted ICU
      length of stay varied from 0.86 to 1.26; and resource use from 0.71 to 1.16.
      CONCLUSIONS: A limited number of operative characteristics, the post-operative
      acute physiology score (APS) of APACHE III and patient demographic data can
      predict hospital death rate, ICU length of stay, and resource use immediately
      following coronary by-pass surgery. These estimates may compliment assessments
      based on pre-operative risk factors in order to more precisely evaluate and
      improve the efficacy and efficiency of cardiovascular surgery.

PMID- 7721920
TI  - Cardiac reoperations with a patent internal thoracic artery graft. A double
      challenge?
AB  - Cardiac reoperations remain a challenge. Reoperations in patients with a patent
      internal thoracic artery graft have a double challenge; the patent internal
      thoracic artery graft and the problem of peroperative myocardial protection. Our
      experience in 25 patients is described and discussed.

PMID- 7721921
TI  - Normothermic retrograde cardioplegia is effective in patients with left
      ventricular hypertrophy. A prospective and randomized study.
AB  - Twenty patients with left ventricular hypertrophy (LVH) undergoing isolated
      aortic valve replacement were prospectively randomized to receive either
      continuous retrograde normothermic (n = 8) or intermittent retrograde hypothermic
      (n = 12) methods of myocardial protection. Biopsies of the left ventricular
      septum were evaluated for ultrastructure and assayed for ATP. There was no
      mortality, no requirement for intra-aortic balloon pump nor neurological events
      in any of the patients from either group. Myocardial ATP (warm 23.2 +/- 1.8
      nmol/mg protein; cold 22.4 +/- 1.2 nmol/mg protein; p = 0.72) and myocardial CPK
      MB (warm 43.6 +/- 5.2 U/l; cold 39.0 +/- 2.5 U/l; p = 0.67) were not
      significantly different. Ultrastructure was generally well preserved in the
      biopsies from both groups, with the exception of one patient in the normothermic
      group. Systemic lactate sampled after 40 minutes of cardiopulmonary bypass was
      significantly higher in the normothermic group (warm 3.4 +/- 0.27 mmol/l; cold
      2.3 +/- 0.21 mmol/l; p = 0.01), however, the myocardial lactate production was
      not significantly different between the two groups (extraction ratio; warm 0.01
      +/- 0.3; cold 0.13 +/- 0.1; p = 0.45). We conclude that the continuous
      normothermic retrograde method of myocardial protection is effective in patients
      with left ventricular hypertrophy; however, the higher systemic lactate levels
      using this technique raises concerns regarding the adequacy of systemic perfusion
      at 37 degrees C.

PMID- 7721922
TI  - Hyperstimulation of leukocytes by plasma from cardiopulmonary by-pass patients is
      diminished by morphine and IL-10 pretreatment.
AB  - OBJECTIVE: The trauma of cardiopulmonary by-pass (CPB) in cardiac surgery results
      in a whole body diffuse inflammatory response characterized in part by
      hyperstimulation of leukocytes. Partially this is due to an increase in the
      release of biological response modifiers such as cytokines, as noted by the
      immunocyte stimulatory actions of cell-free plasma obtained postoperatively from
      CPB patients. The present study was conducted to determine whether CPB plasma
      induced immunocyte hyperstimulation can be prevented with naturally occurring
      immune inhibitory substances, specifically, interleukin (IL)-10 and/or morphine.
      EXPERIMENTAL DESIGN: Controlled in vitro study of the application of drugs to
      naive immunocytes to block the exitation caused by CPB-plasma. SETTING:
      University-based tertiary care hospital. PATIENTS: Plasma was obtained from ten
      patients undergoing CPB. Eligibility included admission for elective cardiac
      surgery, which no chronic illnesses or acute processes. INTERVENTIONS: Monocytes
      and granulocytes were pretreated with IL-10 and/or morphine before exposure to
      plasma obtained from patients undergoing CPB, as CPB-plasma would stimulate naive
      monocytes and granulocytes in a manner similar to that previously reported in CPB
      patients. MEASURES: Computer-assisted microscopic image analysis, measuring
      cellular conformational and velocity changes, was used to evaluate the effect of
      treatment on the immunocytes response to stimulation with CPB-plasma. RESULTS:
      Pretreatment of cells with IL-10 and/or morphine significantly diminished the
      hyperstimulation induced by CPB-plasma in a concentration-dependent manner. In
      contrast, when the cells were initially or simultaneously exposed to CPB-plasma,
      IL-10 and/or morphine had no effect.

PMID- 7721923
TI  - Aortic arch surgery: pros and cons of selective cerebral perfusion. A
      multivariable analysis for cerebral injury during hypothermic circulatory arrest.
AB  - Thirty-five consecutive patients with aortic arch aneurysm who required surgical
      reconstruction were operated on with the aid of extracorporeal circulation
      between February 1985 and December 1993. Nineteen patients (54.3%) were treated
      with hypothermic circulatory arrest (HCA) (Group A) and 16 (45.7%) (Group B) with
      HCA and selective cerebral perfusion (SCP) through the carotid arteries.
      Preoperative characteristics didn't show any significant differences between the
      two groups: mean age was 58.7 +/- 12 vs 62.1 +/- 7, p = ns, male sex 73.6% vs
      75%, p = ns; atherosclerotic aneurysms were 57.8% vs 43.7%, p = ns; Type A
      dissections 42.2% vs 56.3%, p = ns and emergency operation were 68.4% vs 43.7%, p
      = ns in Groups A and B respectively. For SCP, blood was infused initially at a
      rate of 200-300 ml/min, maintaining the 30-40% of cerebral blood flow in
      normothermia, successively, with the aid of transcranial Doppler sonography (TDS)
      SCP-flow was improved to 500-1000 ml/min. The MHz pulsed TDS was used to measure
      the middle cerebral artery flow velocity in deep hypothermia before the arrest,
      in order to adjust the SCP flow during the HCA. In all patients we used open
      aortic anastomosis; in two cases an extraanatomical ascending-descending aorta
      was required, and in other two the "elephant trunk" technique was used in case of
      combined aortic arch and descending aneurysms. The HCA times were similar in the
      two groups 47.5 +/- 22 vs 47.7 +/- 78, p = ns. Early deaths occurred in 5
      patients of the Group A (26.3%) and in 3 patients of the group B (18.7%), p =
      ns.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721924
TI  - Myocardial revascularization using the "no-touch" technique, with mild systemic
      hypothermia, in patients with a calcified ascending aorta.
AB  - Modifications in the standard technique for coronary artery bypass grafting are
      recommended in presence of a calcified ascending aorta, to avoid clamp injury or
      atheroembolism. Between January 1991 and August 1994, we used a "no-touch"
      technique in 18 patients undergoing myocardial revascularization, who had a
      heavily calcified and atherosclerotic ascending aorta. Their mean age was 76.1
      years (range 63 to 82 years). Cardiopulmonary bypass with mild systemic
      hypothermia (32 degrees C) was employed in 16 patients; 2 other patients were
      operated upon without cardiopulmonary bypass. The "no-touch" technique avoids all
      types of clamps in the aorta. No cardioplegia was given, and no grafts were
      anastomosed to the aorta. Fifty-two distal anastomoses (mean: 2.9 per patient)
      were performed, using 37 pedicled arterial grafts (22 internal mammary and 15
      gastroepiploic arteries), and 15 free grafts, which were anastomosed proximally
      to the internal mammary artery. There were no postoperative cerebrovascular
      accidents. Three patients died (16.7% overall mortality): 1 died of pneumonia,
      one patient with a large left ventricular aneurysm died in congestive heart
      failure, and one patient with associated aortic insufficiency died in low cardiac
      output. Our experience suggests that using pedicled arterial grafts for
      myocardial revascularization is safe and effective to avoid clamp injury or
      atheroembolism in patients with a calcified aorta. Deep hypothermia is not
      necessary when using the "no-touch" technique.

PMID- 7721926
TI  - Histological change in cryopreserved rat aortic allograft.
AB  - In this study, we established an experimental cryopreserved aortic allograft
      model in rats and examined the long-term histological changes in the allograft.
      The thoracic aorta of Brown Norway rats (RT1n) was cryopreserved with 10%
      dimethylsulfoxide using a programmable freezer, and was allo-transplanted to the
      infrarenal abdominal aorta of Lewis rats (RT1l). Neither immunosuppressants nor
      anticoagulants were administered postoperatively. As a control, isografting was
      also performed between Lewis donor and recipient rats. In the allograft groups,
      cellular infiltration in the adventitia was massive at the acute phase after the
      operation and decreased gradually. Intimal thickening was predominantly observed
      from the early stage, followed by advancing thickening. In the media, decrease in
      cell number was detected after 1 month, and chondrocyte-like-cells were observed
      around which calcification was noted. Endothelial cells were observed in only one
      third of the recipient investigated at 10 days and in over 80% of those at 12
      months. In the isograft groups, a low grade of intimal thickening was detected
      over the experimental period. No decrease in cell number in the media was
      detected, and the degree of cellular infiltration in the adventitia was mild.
      After allotransplantation of the cryopreserved rat aorta, intimal thickening,
      medial necrosis and cellular infiltration in the adventitia, all the
      manifestations of rejection, occurred. Thus, as the cryopreserved tissue induces
      an immunological response, it is important to match the blood type and/or
      histocompatibility in clinical use.

PMID- 7721927
TI  - Screening of patients with ischemic heart disease by transesophageal atrial
      pacing and the selection of surgical therapy: in patients with arteriosclerosis
      obliterans and aortic aneurysm.
AB  - This study evaluated (1) a screening method for ischemic heart disease (IHD)
      using transesophageal atrial pacing (TEP), and (2) the appropriate surgical
      therapy for patients with concomitant IHD which was evaluated on the basis of the
      coronary score (CS) by Leaman. Thirty-nine patients with arteriosclerosis
      obliterans of the lower extremities (ASO) and 35 with aortic aneurysm underwent
      TEP and coronary angiography (CAG). Coexistent IHD was diagnosed in 25 patients
      (64%) with ASO and in 14 (40%) with aortic aneurysm. Screening for IHD by TEP was
      96% sensitive, 71% specific, and 87% accurate in patients with ASO, and 79%
      sensitive, 90% specific, and 86% accurate in patients with aortic aneurysm.
      Coronary artery bypass grafting (CABG) and peripheral arterial revascularization
      (PAR) were performed by one stage surgery in 3 patients with a CS of 16 or more.
      In 18 patients with a CS of 5.5 or less, only PAR was performed. One stage
      surgery was performed in 6 patients with aortic aneurysm. Four patients had a CS
      of 9.5 or more, and 2 patients with coexistent stenosis of the left anterior
      descending branch (LAD) had CS of 3.5 and 8, respectively. Repair of the aneurysm
      was undertaken in 5 patients with a CS of 8 or less without LAD disease. In
      patients with ASO showing a CS of 5.5 or less and in those with aortic aneurysm
      showing a CS of 8 or less (and without LAD disease), the only surgical procedure
      performed was either PAR or repair of the aneurysm. There were no complications
      attributable to IHD observed in these patients during the perioperative period.

PMID- 7721925
TI  - Effect of low left ventricular ejection fractions on the outcome of primary
      coronary by-pass grafting in end-stage coronary artery disease.
AB  - Advanced ischemic heart disease (HID) with very low left ventricular ejection
      fraction (LVEF), pulmonary hypertension (PHT) with or/without left ventricular
      aneurysm (LVA) are criteria for defining end-stage coronary artery disease
      (ESCAD). Coronary artery by-pass grafting is often denied to these patients.
      Between January 1990 and December 1993, 91 patients with ESCAD, significant 2 or
      3-vessel disease (stenosis > or = 70%) and LVEF < or = 25% underwent primary CABG
      at our institutions. The mean age was 62.5 +/- 8.0 years (41-81), 89% were men.
      Eighty-one patients were in preoperative NYHA (New York Heart Association)
      functional class 3 and 4. Mean LVEF was 21.3 +/- 3.8% (10-25). Mitral
      regurgitation (MR) was present in 39/91 (43%). The systolic pulmonary artery
      pressure (PAP) was 33.2 +/- 17.1 mmHg (11-75) and the wedge pressure was 19.0 +/-
      10.8 mmHg (5-47). Twenty-two patients had significant PHT with a systolic PAP >
      or = 40 mmHg. The overall perioperative mortality was 14.3% (13/91). Low
      postoperative cardiac output occurred in 33 patients, requiring intraaortic
      balloon support in 13. Gastrointestinal complications occurred in 6 patients and
      neurological events in one. Fifteen patients had additional left ventricular
      aneurysm repair. There was a good correlation between LVEF and PAP (r = 0.782).
      Surprisingly, in a subset of patients with preoperative PHT and LVEF < or = 25%
      the mortality rate was only 4.6% (1/22). Other perioperative complications did
      not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721928
TI  - Current strategy of circulatory support for profound heart failure.
AB  - The purpose of this study is to assess the current strategy of mechanical
      circulatory support for profound heart failure. In the last 10 years, 37 patients
      with profound heart failure underwent mechanical circulatory support after open
      heart surgery and 9 patients with non-cardiotomy cardiogenic shock received
      emergency circulatory support. All patients showed severe cardiac failure and/or
      fatal ventricular arrhythmia and required circulatory support as a life-saving
      measure. After cardiovascular surgery, 12 of those patients underwent
      venoarterial bypass (VAB), 13 had biventricular bypass (BVB), 8 had left
      ventricular bypass (LVB) and the remaining 4 patients received left ventricular
      assist device (LVAD). And 9 patients with non-cardiotomy cardiogenic shock
      received percutaneous cardiopulmonary support (or PCPS) as an emergency assist
      system. Weaning and discharge rates of the patients by the type of circulatory
      supports were 41.7% and 25.0% with VAB, 69.3% and 46.2% with BVB, 87.5% and 37.5%
      with LVB, 75.0% and 50.0% with LVAD, and 44.4% and 11.1% with PCPS, respectively.
      Clinical results of post-cardiotomy circulatory support (64.9% of weaning and
      37.8% of discharge) were acceptable, but the patients with non-cardiotomy cardiac
      failure needed early application of more advanced circulatory support.

PMID- 7721929
TI  - Successful repair of complete sternal cleft associated with congenital heart
      disease. Report of one case.
AB  - Total failure of sternal fusion without other developmental anomalies of the
      chest and abdominal wall is rare. We report on a 52-year-old man with a total
      cleft sternum associated exclusively with an ostium secundum type atrial septal
      defect, a large cono-ventricular septal defect and pulmonary stenosis, who
      underwent successful surgical repair of the congenital heart disease and of the
      sternal anomaly by direct approximation of the freshened sternal remnants to the
      midline without interposition of tissue graft or inert prosthesis. This technique
      should be considered and attempted first as a better surgical option even in
      adult patients.

PMID- 7721930
TI  - Cryopreserved small-diameter arterial allografts for arterial by-pass procedures:
      an experimental study.
AB  - The search of small-caliber vascular prosthesis for myocardial revascularization
      and arterial reconstruction has led to an investigation of cryopreserved arterial
      allografts in a sheep model. Carotid arteries with an internal diameter of 4 mm
      and length of 10 cm were harvested from donor sheep and soaked immediately in a
      cold saline solution. Nine arteries were cryopreserved in a nutrient media
      containing 10% DMSO as cryoprotectant and then were stored in a liquid nitrogen
      vapor at -150 degrees C to -170 degrees C. In recipient sheep from different
      species, arterial substitution of a 10 cm segment of carotid artery was realised
      by implantation of fresh (n = 9) or cryopreserved (n = 9) carotid artery
      allografts. After 3 months, the allografts were harvested. In both groups: 7/9
      were patent at the time of explantation. Components of arterial allograft
      rejection were observed in most fresh and cryopreserved arteries: intimal
      thickening with cell proliferation was seen in fresh (3/7) and cryopreserved
      (4/8) arteries; Loss of smooth muscle medial cells was constant; Adventitia was
      involved by a marked inflammatory reaction. A non cellular fibrous intimal
      thickening and presence of large medial calcifications were essentially observed
      in cryopreserved arteries. In conclusion, these results show that at three months
      post implantation, there is little difference in the outcome of fresh and
      cryopreserved arterial allografts. Cryopreservation does not reduce the apparent
      antigenicity of small diameter arterial allografts.

PMID- 7721931
TI  - Multiple cholesterol embolization syndrome: a lethal complication of vascular
      procedures. Report of two histologically proven cases.
AB  - Two cases of multiple cholesterol embolization syndrome (MCES) leading to death
      are presented. Rarely described and labeled as a "great masquerader", its
      presence in the medical literature is growing, since it is best diagnosed, but
      despite the high frequency with which MCES may occur, only a few cases are
      reported. This syndrome is not universally recognised.

PMID- 7721932
TI  - Ultrastructural damage of the pulmonary endothelial cell after storage in lung
      preservation solutions. Comparison between Belzer and Euro-Collins solutions.
AB  - The preservation of the lung for transplantation for a long period is still a
      problem not solved. Euro-Collins (EC) and Belzer (UW) solution are the most
      widely used. The aim of this work is to analyse the direct influence of both EC
      and UW solutions on endothelial cells of human pulmonary artery by means of an
      ultrastructural analysis. The arteries were obtained from 3 patients that
      underwent pneumonectomy and prepared with the no touch technique. The arteries
      were divided in 15 specimens and preserved in EC and UW solution at 4 degrees C
      for 6 and 10 hours. The specimens were fixed in osmic acid veronal buffer 1% and
      embedded in Durcupan. Ultrastructural examination was done with transmission
      electron microscopy (TEM) and the influence of the solutions was evaluated using
      a grading scale with scores ranging from 0 to 4 that express the damages of the
      cellular wall, mitochondria and nuclei. The data are expressed as mean +/-
      standard deviation (n = 5). Student's t-test was used for statistical comparison
      between the solutions. RESULTS: after 6 hours of preservation in EC and UW the
      scores were 5.2 +/- 0.45 and 4.8 +/- 0.84 (p = 0.373) while after 10 hours were
      respectively 8.2 +/- 0.84 and 6.8 +/- 0.84 (p = 0.029). In conclusion our
      experimental model suggests that there are no significant differences between EC
      and UW after hypothermic 6 hours preservation while endothelial cells are better
      preserved after 10 hours in UW solution.

PMID- 7721933
TI  - Hemangioma of the rib. A case report.
AB  - A case of hemangioma of the left twelfth rib is presented. clinical presentation,
      radiologic appearance and differential diagnosis with other vascular tumors of
      the bone are discussed, along with a review of the literature.

PMID- 7721934
TI  - Rhabdomyosarcoma of the oesophagus. A case report.
AB  - A rare case of rhabdomyosarcoma of the oesophagus is presented. The clinical,
      radiologic, and histopathologic features are reviewed. A review of the literature
      revealed only thirteen cases of this type.

PMID- 7721935
TI  - Enzymatic product formation impairs both the chloroplast receptor-binding
      function as well as translocation competence of the NADPH: protochlorophyllide
      oxidoreductase, a nuclear-encoded plastid precursor protein.
AB  - The key enzyme of chlorophyll biosynthesis in higher plants, the light-dependent
      NADPH:protochlorophyllide oxidoreductase (POR, EC 1.6.99.1), is a nuclear-encoded
      plastid protein. Its posttranslational transport into plastids of barley depends
      on the intraplastidic availability of one of its substrates, protochlorophyllide
      (PChlide). The precursor of POR (pPOR), synthesized from a corresponding full
      length barley cDNA clone by coupling in vitro transcription and translation, is
      enzymatically active and converts PChlide to chlorophyllide (Chlide) in a light-
      and NADPH-dependent manner. Chlorophyllide formed catalytically remains tightly
      but noncovalently bound to the precursor protein and stabilizes a transport
      incompetent conformation of pPOR. As shown by in vitro processing experiments,
      the chloroplast transit peptide in the Chlide-pPOR complex appears to be masked
      and thus is unable to physically interact with the outer plastid envelope
      membrane. In contrast, the chloroplast transit peptide in the naked pPOR (without
      its substrates and its product attached to it) and in the pPOR-substrate
      complexes, such as pPOR-PChlide or pPOR-PChlide-NADPH, seems to react
      independently of the mature region of the polypeptide, and thus is able to bind
      to the plastid envelope. When envelope-bound pPOR-PChlide-NADPH complexes were
      exposed to light during a short preincubation, the enzymatically produced Chlide
      slowed down the actual translocation step, giving rise to the sequential
      appearance of two partially processed translocation intermediates. However,
      ongoing translocation induced by feeding the chloroplasts delta-aminolevulinic
      acid, a precursor of PChlide, was able to override these two early blocks in
      translocation, suggesting that the plastid import machinery has a substantial
      capacity to denature a tightly folded, envelope-bound precursor protein.
      Together, our results show that pPOR with Chlide attached to it is impaired both
      in the ATP-dependent step of binding to a receptor protein component of the outer
      chloroplast envelope membrane, as well as in the PChlide-dependent step of
      precursor translocation.

PMID- 7721936
TI  - The capacity to retrieve escaped ER proteins extends to the trans-most cisterna
      of the Golgi stack.
AB  - To explore how far into the Golgi stack the capacity to retrieve KDEL proteins
      extends, we have introduced an exogenous probe (the peptide YHPNSTCSEKDEL) into
      the TGN of living cells. For this purpose, a CHO cell line expressing a c-myc
      tagged version of the transmembrane protein TGN38--which cycles between the TGN
      and the cell surface--was generated. The cells internalized peptides that were
      disulfide bonded to anti-myc antibodies and accumulated the peptide-antibody
      complexes in the TGN. Peptides released from these complexes underwent retrograde
      transport to the ER, as evidenced by the transfer of N-linked carbohydrate to
      their acceptor site. The KDEL-tagged glycopeptides (approximately 10% of the
      endocytosed load) behaved like endogenous ER residents: they stayed
      intracellular, and their oligosaccharide side chains remained sensitive to
      endoglycosidase H. An option thus exists to extract ER residents even at the most
      distant pole of the Golgi stack, suggesting that sorting of resident from
      exported ER proteins may occur in a multistage process akin to fractional
      distillation.

PMID- 7721937
TI  - Vesicle-mediated protein transport: regulatory interactions between the Vps15
      protein kinase and the Vps34 PtdIns 3-kinase essential for protein sorting to the
      vacuole in yeast.
AB  - A membrane-associated complex composed of the Vps15 protein kinase and the Vps34
      phosphatidylinositol 3-kinase (PtdIns 3-kinase) is essential for the delivery of
      proteins to the yeast vacuole. An active Vps15p is required for the recruitment
      of Vps34p to the membrane and subsequent stimulation of Vps34p PtdIns 3-kinase
      activity. Consistent with this, mutations altering highly conserved residues in
      the lipid kinase domain of Vps34p lead to a dominant-negative phenotype resulting
      from titration of activating Vps15 proteins. In contrast, catalytically inactive
      Vps15p mutants do not produce a dominant mutant phenotype because they are unable
      to associate with Vps34p in a wild-type manner. These data indicate that an
      intact Vps15p protein kinase domain is necessary for the association with and
      activation of Vps34p, and they demonstrate that a functional Vps15p-Vps34p
      complex is absolutely required for the efficient delivery of proteins to the
      vacuole. Analysis of a temperature-conditional allele of VPS15, in which a shift
      to the nonpermissive temperature leads to a decrease in cellular PtdIns(3)P
      levels, indicates that the loss of Vps15p function leads to a defect in
      activation of Vps34p. In addition, characterization of a temperature-sensitive
      allele of VPS34 demonstrates that inactivation of Vps34p leads to the immediate
      missorting of soluble vacuolar proteins (e.g., carboxypeptidase Y) without an
      apparent defect in the sorting of the vacuolar membrane protein alkaline
      phosphatase. This rapid block in vacuolar protein sorting appears to be the
      result of loss of PtdIns 3-kinase activity since cellular PtdIns(3)P levels
      decrease dramatically in vps34 temperature-sensitive mutant cells that have been
      incubated at the nonpermissive temperature. Finally, analysis of the defects in
      cellular PtdIns(3)P levels in various vps15 and vsp34 mutant strains has led to
      additional insights into the importance of PtdIns(3)P intracellular localization,
      as well as the roles of Vps15p and Vps34p in vacuolar protein sorting.

PMID- 7721938
TI  - The urokinase-type plasminogen activator receptor, a GPI-linked protein, is
      localized in caveolae.
AB  - The urokinase plasminogen activator receptor (uPAR), a
      glycosylphosphatidylinositol-linked glycoprotein, plays a central role in the
      regulation of pericellular proteolysis and participates in events leading to cell
      activation. Here, we demonstrate that uPAR, on a human melanoma cell line, is
      localized in caveolae, flask-shaped microinvaginations of the plasma membrane
      found in a variety of cell types. Indirect immunofluorescence with anti-uPAR
      antibodies on the melanoma cells showed a punctated staining pattern that
      accumulated to stretches along sides of cell-cell contact and membrane ruffles.
      uPAR colocalized with caveolin, a characteristic protein in the coat of caveolae,
      as demonstrated by double staining with specific antibodies. Further, uPAR could
      be directly localized in caveolae by in vivo immunoelectron microscopy. Both uPAR
      and its ligand, uPA, were present in caveolae enriched low density Triton X-100
      insoluble complexes, as shown by immunoblotting. From such complexes, caveolin
      could be coprecipitated with uPAR-specific antibodies suggesting a close spatial
      association between uPAR and caveolin that might have implications for the signal
      transduction mediated by uPAR. Further, functional studies indicated that the
      localization of uPAR and its ligand in caveolae enhances pericellular plasminogen
      activation, since treatment of the cells with drugs that interfere with the
      structural integrity of caveolae, such as nystatin, markedly reduced cell surface
      plasmin generation. Thus, caveolae promote efficient cell surface plasminogen
      activation by clustering uPAR, uPA, and possibly other protease receptors in one
      membrane compartment.

PMID- 7721939
TI  - Pmp27 promotes peroxisomal proliferation.
AB  - Peroxisomes perform many essential functions in eukaryotic cells. The weight of
      evidence indicates that these organelles divide by budding from preexisting
      peroxisomes. This process is not understood at the molecular level. Peroxisomal
      proliferation can be induced in Saccharomyces cerevisiae by oleate. This growth
      substrate is metabolized by peroxisomal enzymes. We have identified a protein,
      Pmp27, that promotes peroxisomal proliferation. This protein, previously termed
      Pmp24, was purified from peroxisomal membranes, and the corresponding gene,
      PMP27, was isolated and sequenced. Pmp27 shares sequence similarity with the
      Pmp30 family in Candida boidinii. Pmp27 is a hydrophobic peroxisomal membrane
      protein but it can be extracted by high pH, suggesting that it does not fully
      span the bilayer. Its expression is regulated by oleate. The function of Pmp27
      was probed by observing the phenotype of strains in which the protein was
      eliminated by gene disruption or overproduced by expression from a multicopy
      plasmid. The strain containing the disruption (3B) was able to grow on all carbon
      sources tested, including oleate, although growth on oleate, glycerol, and
      acetate was slower than wild type. Strain 3B contained peroxisomes with all of
      the enzymes of beta-oxidation. However, in addition to the presence of a few
      modestly sized peroxisomes seen in a typical thin section of a cell growing on
      oleate-containing medium, cells of strain 3B also contained one or two very large
      peroxisomes. In contrast, cells in a strain in which Pmp27 was overexpressed
      contained an increased number of normal-sized peroxisomes. We suggest that Pmp27
      promotes peroxisomal proliferation by participating in peroxisomal elongation or
      fission.

PMID- 7721940
TI  - Specific receptor detection by a functional keratinocyte growth factor
      immunoglobulin chimera.
AB  - Fibroblast growth factor receptors (FGFRs) are encoded by at least four distinct
      highly conserved genes, and alternative splicing generates multiple gene
      products. The close relationship among different FGFRs has greatly increased the
      difficulty in generating specific immunochemical probes. As an alternative
      strategy, we constructed a fusion protein comprising keratinocyte growth factor
      (KGF) and an IgG1 Fc domain (HFc). The chimeric molecule was efficiently secreted
      from transfectants as a disulfide-linked dimer that bound KGFRs with high
      affinity. Moreover, the KGF-HFc, like native KGF, induced DNA synthesis by
      epithelial cells implying normal functional receptor activation. Because it
      retained the convenient detection properties of an immunoglobulin, it was
      possible to use the KGF-HFc in ligand-mediated histochemical analysis of KGFRs.
      Flow cytometry revealed KGF-HFc chimera detection of the KGFR, an alternative
      FGFR2 product, but not FGFR1 (flg) or FGFR2 (bek). Histochemical analysis of
      normal skin demonstrated the specific localization of KGFRs within the spinous
      layer, a zone of epithelial cell differentiation. KGFRs were also localized to
      epithelial cells within a specific region of the hair follicle, and they were not
      detectable in cells of the sweat gland. Tissue sections of soft palate and
      tonsil, two examples of nonkeratinizing epithelium, revealed staining of stratum
      spinosum and some staining of the basal cell layer as well. Neither salivary
      gland epithelium nor lymphoid cells were positive. The ciliated epithelium of the
      trachea exhibited KGFR expression in intermediate and basal cell layers. In
      striking contrast to the normal pattern of staining in the adjacent epithelium, a
      squamous cell carcinoma of skin lacked detectable KGFRs. Our present findings
      suggest that growth factor-Ig fusion proteins may be generally applicable in
      ligand-mediated histochemical detection and localization of growth factor
      receptors.

PMID- 7721941
TI  - Cytoskeletal rearrangements and the functional role of T-plastin during entry of
      Shigella flexneri into HeLa cells.
AB  - Shigella flexneri is an enteroinvasive bacterium which causes bacillary dysentery
      in humans. A major feature of its pathogenic potential is the capacity to invade
      epithelial cells. Shigella entry into epithelial cells is considered a parasite
      induced internalization process requiring polymerization of actin. Here we
      describe the cytoskeletal rearrangements during S. flexneri invasion of HeLa
      cells. After an initial contact of the bacterium with the cell surface, distinct
      nucleation zones of heavy chain actin polymerization appear in close proximity to
      the contact site underneath the parasite with long filaments being polymerized.
      These structures then push cellular protrusions that rise beside the entering
      bacterium, being sustained by tightly bundled long actin filaments organized in
      parallel orientation with their positive ends pointing to the cytoplasmic
      membrane. Finally, the cellular projections coalesce above the bacterial body,
      leading to its internalization. In addition, we found the actin-bundling protein
      plastin to be concentrated in these protrusions. Since plastin is known to bundle
      actin filaments in parallel orientation, colocalization of parallel actin
      filaments and plastin in the cellular protrusions strongly suggested a functional
      role of this protein in the architecture of parasite-induced cellular
      projections. Using transfection experiments, we show the differential recruitment
      of the two plastin isoforms (T- and L-) into Shigella entry zones. By transient
      expression of a truncated T-plastin which is deprived of one of its actin-binding
      sites, we also demonstrate the functional role of T-plastin in Shigella entry
      into HeLa cells.

PMID- 7721942
TI  - Myosin light chain 3F regulatory sequences confer regionalized cardiac and
      skeletal muscle expression in transgenic mice.
AB  - The myosin light chain IF/3F locus contains two independent promoters, MLC1F and
      MLC3F, which are differentially activated during skeletal muscle development.
      Transcription at this locus is regulated by a 3' skeletal muscle enhancer
      element, which directs correct temporal and tissue-specific expression from the
      MLC1F promoter in transgenic mice. To investigate the role of this enhancer in
      regulation of the MLC3F promoter in vivo, we have analyzed reporter gene
      expression in transgenic mice containing lacZ under transcriptional control of
      the mouse MLC3F promoter and 3' enhancer element. Our results show that these
      regulatory elements direct strong expression of lacZ in skeletal muscle; the
      transgene, however, is activated 4-5 d before the endogenous MLC3F promoter, at
      the time of initiation of MLC1F transcription. In adult mice, transgene activity
      is downregulated in muscles that have reduced contributions of type IIB fibers
      (soleus and diaphragm). The rostrocaudal positional gradient of transgene
      expression documented for MLC1F transgenic mice (Donoghue, M., J. P. Merlie, N.
      Rosenthal, and J. R. Sanes. 1991. Proc. Natl. Acad. Sci. USA. 88:5847-5851) is
      not seen in MLC3F transgenic mice. Although MLC3F was previously thought to be
      restricted to skeletal striated muscle, the MLC3F-lacZ transgene is expressed in
      cardiac muscle from 7.5 d of development in a spatially restricted manner in the
      atria and left ventricular compartments, suggesting that transcriptional
      differences exist between cardiomyocytes in left and right compartments of the
      heart. We show here that transgene-directed expression of the MLC3F promoter
      reflects low level expression of endogenous MLC3F transcripts in the mouse heart.

PMID- 7721943
TI  - Differential methylation and altered conformation of cytoplasmic and nuclear
      forms of protein phosphatase 2A during cell cycle progression.
AB  - Protein phosphatase 2A (PP2A) appears to be involved in the regulation of many
      cellular processes. Control mechanisms that lead to the activation (and
      deactivation) of the various holoenzymes to initiate appropriate
      dephosphorylation events remain obscure. The core components of all PP2A
      holoenzymes are the catalytic (PP2Ac) and 63-65-kD regulatory (PR65) subunits.
      Monospecific and affinity-purified antibodies against both PP2Ac and PR65 show
      that these proteins are ubiquitously localized in the cytoplasm and the nucleus
      in nontransformed fibroblasts. As determined by quantitative immunofluorescence
      the core subunits of PP2A are twofold more concentrated in the nucleus than in
      the cytoplasm. Detailed analysis of synchronized cells reveals striking changes
      in the nuclear to cytoplasmic ratio of PP2Ac-specific immunoreactivity albeit the
      total amounts of neither PP2Ac nor PR65 in each compartment alters significantly
      during the cell cycle. Our results imply that differential methylation of PP2Ac
      occurs at the G0/G1 and G1/S boundaries. Specifically a demethylated form of
      PP2Ac is found in the cytoplasm of G1 cells, and in the nucleus of S and G2
      cells. In addition nuclear PP2A holoenzymes appear to undergo conformational
      changes at the G0/G1 and G1/S boundaries. During mitosis PP2A is lost from the
      nuclear compartment, and unlike protein phosphatase 1 shows no specific
      association with the condensed chromatin.

PMID- 7721944
TI  - Two distinct functions of the carboxyl-terminal tail domain of NF-M upon
      neurofilament assembly: cross-bridge formation and longitudinal elongation of
      filaments.
AB  - Neurofilaments are the major cytoskeletal elements in the axon that take highly
      ordered structures composed of parallel arrays of 10-nm filaments linked to each
      other with frequent cross-bridges, and they are believed to maintain a highly
      polarized neuronal cell shape. Here we report the function of rat NF-M in this
      characteristic neurofilament assembly. Transfection experiments were done in an
      insect Sf9 cell line lacking endogenous intermediate filaments. NF-L and NF-M
      coassemble to form bundles of 10-nm filaments packed in a parallel manner with
      frequent cross-bridges resembling the neurofilament domains in the axon when
      expressed together in Sf9 cells. Considering the fact that the expression of
      either NF-L or NF-M alone in these cells results in neither formation of any
      ordered network of 10-nm filaments nor cross-bridge structures, NF-M plays a
      crucial role in this parallel filament assembly. In the case of NF-H the carboxyl
      tail domain has been shown to constitute the cross-bridge structures. The
      similarity in molecular architecture between NF-M and NF-H suggests that the
      carboxyl-terminal tail domain of NF-M also constitutes cross-bridges. To examine
      this and to further investigate the function of the carboxyl-terminal tail domain
      of NF-M, we made various deletion mutants that lacked part of their tail domains,
      and we expressed these with NF-L. From this deletion mutant analysis, we conclude
      that the carboxyl-terminal tail domain of NF-M has two distinct functions. First,
      it is the structural component of cross-bridges, and these cross-bridges serve to
      control the spacing between core filaments. Second, the portion of the carboxyl
      terminal tail domain of NF-M that is directly involved in cross-bridge formation
      affects the core filament assembly by helping them to elongate longitudinally so
      that they become straight.

PMID- 7721945
TI  - Trafficking of cell surface beta-amyloid precursor protein: retrograde and
      transcytotic transport in cultured neurons.
AB  - Amyloid beta-protein (A beta), the principal constituent of senile plaques seen
      in Alzheimer's disease (AD), is derived by proteolysis from the beta-amyloid
      precursor protein (beta PP). The mechanism of A beta production in neurons, which
      are hypothesized to be a rich source of A beta in brain, remains to be defined.
      In this study, we describe a detailed localization of cell surface beta PP and
      its subsequent trafficking in primary cultured neurons. Full-length cell surface
      beta PP was present primarily on perikarya and axons, the latter with a
      characteristic discontinuous pattern. At growth cones, cell surface beta PP was
      inconsistently detected. By visualizing the distribution of beta PP monoclonal
      antibodies added to intact cultures, beta PP was shown to be internalized from
      distal axons or terminals and retrogradely transported back to perikarya in
      organelles which colocalized with fluid-phase endocytic markers. Retrograde
      transport of beta PP was shown in both hippocampal and peripheral sympathetic
      neurons, the latter using a compartment culture system that isolated cell bodies
      from distal axons and terminals. In addition, we demonstrated that beta PP from
      distal axons was transcytotically transported to the surface of perikarya from
      distal axons in sympathetic neurons. Indirect evidence of this transcytotic
      pathway was obtained in hippocampal neurons using antisense oligonucleotide to
      the kinesin heavy chain to inhibit anterograde beta PP transport. Taken together,
      these results demonstrate novel aspects of beta PP trafficking in neurons,
      including retrograde axonal transport and transcytosis. Moreover, the axonal
      predominance of cell surface beta PP is unexpected in view of the recent report
      of polarized sorting of beta PP to the basolateral domain of MDCK cells.

PMID- 7721946
TI  - Autocrine motility factor receptor is a marker for a distinct membranous tubular
      organelle.
AB  - Autocrine motility factor (AMF) is secreted by tumor cells and is capable of
      stimulating the motility of the secreting cells. In addition to being expressed
      on the cell surface, its receptor, AMF-R, is found within a Triton X-100
      extractable intracellular tubular compartment. AMF-R tubules can be distinguished
      by double immunofluorescence microscopy from endosomes labeled with the
      transferrin receptor, lysosomes labeled with LAMP-2, and the Golgi apparatus
      labeled with beta-COP. AMF-R can also be separated from a LAMP-2 containing
      lysosomal fraction by differential centrifugation of MDCK cells and is found
      within a 100,000 g membrane pellet. By electron microscopic immunocytochemistry,
      AMF-R is localized predominantly to smooth vesicular and tubular membranous
      organelles as well as to a lesser extent to the plasma membrane and rough
      endoplasmic reticulum. AMF-R tubules have a variable diameter of 50-250 nm and
      can acquire an elaborate branched morphology. By immunofluorescence microscopy,
      AMF-R tubules are clearly distinguished from the calnexin labeled rough
      endoplasmic reticulum and AMF-R tubule expression is stable to extended
      cycloheximide treatment. The AMF-R tubule is therefore not a biosynthetic
      subcompartment of the endoplasmic reticulum. The tubular morphology of the AMF-R
      tubule is modulated by both the actin and microtubule cytoskeletons. In a similar
      fashion to that described previously for the tubular lysosome and endoplasmic
      reticulum, the linear extension and peripheral cellular orientation of the AMF-R
      tubule are dependent on the integrity of the microtubule cytoskeleton. The AMF-R
      tubule may thus form part of a family of microtubule-associated tubular
      organelles.

PMID- 7721947
TI  - A recombinant tail-less integrin beta 4 subunit disrupts hemidesmosomes, but does
      not suppress alpha 6 beta 4-mediated cell adhesion to laminins.
AB  - To examine the function of the alpha 6 beta 4 integrin we have determined its
      ligand-binding ability and overexpressed two potentially dominant negative mutant
      beta 4 subunits, lacking either the cytoplasmic or extracellular domain, in
      bladder epithelial 804G cells. The results of cell adhesion and radioligand
      binding assays showed that alpha 6 beta 4 is a receptor for several laminin
      isoforms, including laminin 1, 2, 4, and 5. Overexpression of the tail-less or
      head-less mutant beta 4 subunit did not suppress alpha 6 beta 4-mediated adhesion
      to laminins, as both types of transfectants adhered to these ligands in the
      presence of blocking anti-beta 1 antibodies as well as the controls. However,
      immunofluorescence experiments indicated that the endogenous alpha 6 beta 4
      integrin and other hemidesmosomal markers were not concentrated in hemidesmosomes
      in cells overexpressing tail-less beta 4, while the distribution of these
      molecules was not altered in cells overexpressing the head-less subunit. Electron
      microscopic studies confirmed that cells overexpressing tail-less beta 4 had a
      drastically reduced number of hemidesmosomes, while cells expressing the head
      less subunit had a normal number of these structures. Thus, expression of a tail
      less, but not a head-less mutant beta 4 subunit leads to a dominant negative
      effect on hemidesmosome assembly without suppressing initial adhesion to
      laminins. We conclude that the alpha 6 beta 4 integrin binds to several laminins
      and plays an essential role in the assembly and/or stability of hemidesmosomes,
      that alpha 6 beta 4-mediated adhesion and hemidesmosome assembly have distinct
      requirements, and that it is possible to use a dominant negative approach to
      selectively interfere with a specific function of an integrin.

PMID- 7721950
TI  - Cell transformation by c-Ha-rasVal12 oncogene is accompanied by a decrease in
      histone H1 zero and an increase in nucleosomal repeat length.
AB  - The activated c-Ha-rasVal12 oncogene is often involved in the genesis of human
      malignancies. We show here that in c-Ha-rasVal12 oncogene-transformed mouse NIH
      3T3 fibroblasts the copy number and expression level of the mutant ras oncogene
      correlates with the degree of chromatin decondensation, as assessed by
      micrococcal nuclease (MNase) and DNase I digestion. MNase and DNase I analyses
      further revealed that the nucleosomal repeat lengths were different in the normal
      and ras oncogene-transformed cells, 162.3 bp and 178.1 bp, respectively. These
      chromatin changes were accompanied by alterations in the content of histone H1
      zero. Furthermore, using DNase I as a probe, we discovered that serum stimulation
      of normal and transformed cells, synchronized by serum starvation, induces rapid
      reversible changes in the structure of bulk chromatin that may be linked to
      transcriptional activation. Our data thus indicate that cell transformation by
      ras is associated with specific changes in chromatin structure that make it more
      vulnerable, and prone to additional mutations characteristic of cancer
      development in vivo.

PMID- 7721948
TI  - In vivo analysis of cadherin function in the mouse intestinal epithelium:
      essential roles in adhesion, maintenance of differentiation, and regulation of
      programmed cell death.
AB  - A model system is described for defining the physiologic functions of mammalian
      cadherins in vivo. 129/Sv embryonic stem (ES) cells, stably transfected with a
      dominant negative N-cadherin mutant (NCAD delta) under the control of a promoter
      that only functions in postmitotic enterocytes during their rapid, orderly, and
      continuous migration up small intestinal villi, were introduced into normal
      C57B1/6 (B6) blastocysts. In adult B6<->129/Sv chimeric mice, each villus
      receives the cellular output of several surrounding monoclonal crypts. A
      polyclonal villus located at the boundary of 129/Sv- and B6-derived intestinal
      epithelium contains vertical coherent bands of NCAD delta-producing enterocytes
      plus adjacent bands of normal B6-derived enterocytes. A comparison of the
      biological properties of these cell populations established that NCAD delta
      disrupts cell-cell and cell-matrix contacts, increases the rate of migration of
      enterocytes along the crypt-villus axis, results in a loss of their
      differentiated polarized phenotype, and produces precocious entry into a death
      program. These data indicate that enterocytic cadherins are critical cell
      survival factors that actively maintain intestinal epithelial function in vivo.

PMID- 7721949
TI  - Molecular cloning of chick beta-tectorin, an extracellular matrix molecule of the
      inner ear.
AB  - The tectorial membrane is an extracellular matrix lying over the apical surface
      of the auditory epithelium. Immunofluorescence studies have suggested that some
      proteins of the avian tectorial membrane, the tectorins, may be unique to the
      inner ear (Killick, R., C. Malenczak, and G. P. Richardson. 1992. Hearing Res.
      64:21-38). The cDNA and deduced amino acid sequences for chick beta-tectorin are
      presented. The cDNA encodes a protein of 36,902.6 D with a putative signal
      sequence, four potential N-glycosylation sites, 13 cysteines, and a hydrophobic
      COOH terminus. Western blots of two-dimensional gels using antibodies to a
      synthetic peptide confirm the identity of the cDNA. Southern and Northern
      analysis suggests that beta-tectorin is a single-copy gene only expressed in the
      inner ear. The predicted COOH terminus is similar to that of
      glycosylphosphatidylinositol-linked proteins, and antisera raised to this region
      react with in vitro translation products of the cDNA clone but not with mature
      beta-tectorin. These data suggest beta-tectorin is synthesized as a
      glycosylphosphatidyl-inositol-linked precursor, targeted to the apical surface of
      the sensory epithelium by the lipid moiety, and then further processed. Sequence
      analysis indicates the predicted protein possesses a zona pellucida domain, a
      sequence that is common to a limited number of other matrix-forming proteins and
      may be involved in the formation of filaments. In the cochlear duct, beta
      tectorin is expressed in the basilar papilla, in the clear cells and the cuboidal
      cells, as well as in the striolar region of the lagena macula. The expression of
      beta-tectorin is associated with hair cells that have an apical cell surface
      specialization known as the 275-kD hair cell antigen restricted to the basal
      region of the hair bundle, suggesting that matrices containing beta-tectorin are
      required to drive this hair cell type.

PMID- 7721951
TI  - Platelet talin is phosphorylated by calyculin A.
AB  - Calyculin A and okadaic acid, potent and cell permeable inhibitors of type 1 and
      type 2A protein phosphatases, inhibit platelet aggregation and secretion.
      However, the relationship between phosphatase inhibition and inhibition of
      platelet function is not well understood. We found that in unstimulated
      platelets, talin (P235) was phosphorylated at threonine residues by calyculin A.
      Furthermore, the extent of talin phosphorylation by calyculin A was closely
      correlated with its inhibition of thrombin-induced platelet aggregation. Since
      the binding of talin to platelet glycoprotein IIb/IIIa complex has been shown to
      be affected by its phosphorylation, these results suggest that type 1 and/or type
      2A protein phosphatases may play a role in the regulation of membrane
      cytoskeleton interaction through dephosphorylation of talin.

PMID- 7721953
TI  - Generation of phosphorylcholine as an essential event in the activation of Raf-1
      and MAP-kinases in growth factors-induced mitogenic stimulation.
AB  - Cell proliferation is regulated by an appropriate combination of intracellular
      signals involving activation of kinases and the generation of phospholipid
      metabolites. We report here that growth factors induce a biphasic generation of
      phosphorylcholine (PCho) in quiescent NIH 3T3 cells, resulting in an early and
      transient increase at 100 s and a larger and sustained increase after 3 h of
      stimulation. Generation of PCho at both early and late times of growth factors
      stimulation results from the consecutive activation of phospholipase D (PLD) and
      choline kinase (ChoK). Production of PCho by specific growth factors seems an
      essential requirement for the early signals associated to activation of Raf-1 and
      MAP kinases, since blockage of choline kinase completely inhibited activation of
      Raf-1 and MAP kinases by PDGF or FGF. Both the transient early increase and the
      late sustained increase in PCho are required for the induction of DNA-synthesis,
      besides completion of the activation of the serine/threonine kinases cascade.
      Thus, our results strongly suggest that generation of PCho by the PLD/choline
      kinase pathway is one of the critical steps in regulating cell growth in NIH 3T3
      stimulated by growth factors.

PMID- 7721952
TI  - Inhibition of endothelial cell proliferation by SPARC is mediated through a
      Ca(2+)-binding EF-hand sequence.
AB  - SPARC (secreted protein, acidic and rich in cysteine, also known as osteonectin
      and BM-40) is a metal-binding glycoprotein secreted by a variety of cultured
      cells and characteristic of tissues undergoing morphogenesis, remodeling, and
      repair. Recently it has been shown that SPARC inhibits the progression of the
      endothelial cell cycle in mid-G1, and that a synthetic peptide (amino acids 54-73
      of secreted murine SPARC, peptide 2.1) from a cationic, disulfide-bonded region
      was in part responsible for the growth-suppressing activity [Funk and Sage
      (1991): Proc Natl Acad Sci USA 88:2648-2652]. Moreover, SPARC was shown to
      interact directly with bovine aortic endothelial (BAE) cells through a C-terminal
      EF-hand sequence comprising a high-affinity Ca(2+)-binding site of SPARC and
      represented by a synthetic peptide (amino acids 254-273) termed 4.2 [Yost and
      Sage (1993): J Biol Chem 268:25790-25796]. In this study we show that peptide 4.2
      is a more potent inhibitor of DNA synthesis that acts cooperatively with peptide
      2.1 to diminish the incorporation of [3H]-thymidine by both BAE and bovine
      capillary endothelial (BCE) cells. At concentrations of 0.019-0.26 mM peptide
      4.2, thymidine incorporation by BAE cells was decreased incrementally, relative
      to control values, from approximately 100 to 10%. Although somewhat less
      responsive, BCE cells exhibited a dose-responsive decrement in thymidine
      incorporation, with a maximal inhibition of 55% at 0.39 mM. The inhibitory effect
      of peptide 4.2 was essentially independent of heparin and basic fibroblast growth
      factor and was blocked by anti-SPARC peptide 4.2 IgG, but not by antibodies
      specific for other domains of SPARC. To identify residues that were necessary for
      inhibition of DNA synthesis, we introduced single amino acid substitutions into
      synthetic peptide 4.2 and tested their activities and cell-surface binding
      characteristics on endothelial cells. Two peptides displayed null to diminished
      effects in the bioassays that were concentration-dependent: peptide 4.2 K,
      containing an Asp258 --> Lys substitution, and peptide 4.2 AA, in which the two
      disulfide-bonded Cys (positions 255 and 271) were changed to Ala residues.
      Peptide 4.2 K, which failed to fulfill the EF-hand consensus formula, exhibited
      an anomalous fluorescence emission spectrum, in comparison with the wild-type 4.2
      sequence, that was indicative of a compromised affinity for Ca2(+).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7721954
TI  - Integrity of intermediate filaments is associated with the development of
      acquired thermotolerance in 9L rat brain tumor cells.
AB  - Withangulatin A (WA), a newly discovered withanolide isolated from an antitumor
      Chinese herb, has been shown to be a vimentin intermediate filament-targeting
      drug by using immunofluorescence microscopy. Together with cytochalasin D and
      colchicine, these drugs were employed to investigate the importance of vimentin
      intermediate filaments, actin filaments, and microtubules in the development of
      acquired thermotolerance in 9L rat brain tumor cells treated at 45 degrees C for
      15 min (priming heat-shock). Acquired thermotolerance was abrogated in cells
      incubated with WA before the priming heat-shock but it could be detected in cells
      treated with WA after the priming heat-shock. In contrast, cytochalasin D and
      colchicine do not interfere with the development of thermotolerance at all. The
      intracellular localizations of vimentin and the constitutive heat-shock protein70
      (HSC70) in treated cells were examined by using immunofluorescence microscopy and
      detergent-extractability studies. In cells treated with WA before the priming
      heat-shock, vimentin IFs were tightly aggregated around the nucleus and unable to
      return to their normal organization after a recovery under normal growing
      conditions. In contrast, the IF network in cells treated with WA after the
      priming heat-shock was able to reorganize into filamentous form after a recovery
      period, a behavior similar to that of the cells treated with heat-shock only.
      HSC70 was found to be co-localized with vimentin during these changes. It is
      suggested that the integrity of intermediate filaments is important for the
      development of thermotolerance and that HSC70 may be involved in this process by
      stabilizing the intermediate filaments through direct or indirect binding.

PMID- 7721955
TI  - Rodent myoblast interactions with laminin require cell surface glycoconjugates
      but not laminin glycosyl groups.
AB  - Laminin glycosyl groups are necessary for the spreading of murine melanoma cells
      which become attached to this glycoprotein. Laminin has been implicated in
      myogenesis but the potential role of its glycosyl groups in this process has not
      been examined. In this study we report the effects of the carbohydrate moieties
      of laminin on myoblast adhesion, spreading, and differentiation. Unglycosylated
      laminin from tunicamycin-treated cultures of a mouse cell line, M1536 B3, was
      used in the experiments. Glycosylated laminin from a murine tumor and from
      cultures of M1563 B3 cells served as controls. Cell binding experiments with
      C2C12 mouse myoblasts showed that the cells preferred a laminin-coated surface,
      compared to the uncoated plastic surface (nontissue culture wells). Myoblasts did
      not distinguish between glycosylated and unglycosylated laminin substrates. Both
      glycosylated and unglycosylated forms of laminin promoted myoblast growth and
      differentiation. In contrast, cells on uncoated plastic surfaces grew very slowly
      and did not further differentiate. The L6 rat myoblast response to glycosylated
      and unglycosylated laminin was the same. These results indicate that although
      rodent myoblasts in culture require a laminin substratum for spreading, growth,
      and differentiation on a proprietary plastic surface, laminin carbohydrates are
      not implicated in those cellular responses. In contrast, parallel studies using
      the lectin, Con A, indicate that cell surface glycoconjugates of myoblasts are
      implicated in the response of these cells to a laminin substratum.

PMID- 7721956
TI  - Changes in the sulfation extent of membrane-associated proteoglycans produced by
      Sertoli cells in culture.
AB  - Sertoli cells in culture synthesize two different membrane-associated
      proteoglycans (MA-PG): a proteoglycan containing heparan sulfate (HS) and
      chondroitin sulfate (CS) glycosaminoglycan (GAG) chains and a CS-PG containing
      only CS-GAG chains. The structure of these molecules is regulated by the presence
      of fetal calf serum (FCS) in the culture medium. Changes in the concentration of
      FCS resulted in changes in the total 35SO4 incorporation into MA-PG and a shift
      in the elution profile of each component subjected to ion-exchange
      chromatography. Thus, without FCS, the incorporation was low, while in 1% and 10%
      FCS, the uptake of the precursor was 1.7 and 4.5 times higher, respectively. MA
      PG synthesized by Sertoli cells cultured in 10% FCS eluted from DEAE-Sephacel
      columns at higher salt concentration than the MA-PG synthesized by cells cultured
      in 0% or 1% FCS. Double-labeled experiments showed that the 35SO4/3H-glucosamine
      ratio incorporated into MA-PG produced by Sertoli cells, increased from 17.6 to
      23.6 and 50.9 in cells cultured at 0, 1, and 10% FCS, respectively. However, the
      presence of FCS affected neither the hydrodynamic size nor the chemical nature of
      GAG chains of MA-PG. These results show that changes in the FCS concentration
      promote changes in the sulfation extent of MA-PG molecules produced by Sertoli
      cells.

PMID- 7721957
TI  - Dual mechanism of protein-tyrosine phosphorylation in concanavalin A-stimulated
      platelets.
AB  - Treatment of human platelets with the lectin Concanavalin A (Con A) resulted in
      the tyrosine phosphorylation of several proteins with molecular masses 65, 80,
      85, 95, 120, 135, and 150 kDa. These proteins were divided in two groups: the
      first group included the 65-, 85-, 95-, and 120-kDa bands, which were tyrosine
      phosphorylated also in thrombin-stimulated platelets; the second group (80-, 135
      , and 150-kDa bands) included proteins whose tyrosine phosphorylation was
      exclusively promoted by Con A, but not by thrombin. Members of the second group
      were rapidly dephosphorylated when the lectin was displaced from the cell surface
      by methyl alpha-D-mannopyranoside. Pretreatment of intact platelets with the
      prostacyclin analog iloprost, inhibited Con A-induced tyrosine phosphorylation of
      the first group of proteins, but had no effect on the tyrosine phosphorylation of
      the proteins of the second group. Succinyl-Con A, a dimeric derivative of the
      lectin, which binds to the platelet surface but does not promote clustering of
      the receptor, did not induce tyrosine phosphorylation of the second group of
      proteins, although phosphorylation of some members of the first group was
      observed. Our results demonstrate the presence of two different mechanisms
      leading to protein-tyrosine phosphorylation in Con A-stimulated platelets, and
      identify a new signal transduction pathway, promoted by the clustering of
      membrane glycoproteins, that produces tyrosine phosphorylation of specific
      substrates. This new pathway may be activated by platelet interaction with
      multivalent ligands, such as adhesive proteins, during adhesion, spreading, and
      aggregation.

PMID- 7721958
TI  - TGF-beta regulation of nuclear proto-oncogenes and TGF-beta gene expression in
      normal human osteoblast-like cells.
AB  - Transforming growth factor-beta (TGF-beta) is present in high levels in bone and
      plays an important role in osteoblast growth and differentiation. In order to
      dissect the molecular mechanisms of action of TGF-beta on osteoblasts, the
      effects of TGF-beta on the steady state mRNA levels of c-fos, c-jun, and jun-B
      proto-oncogenes on normal human osteoblast-like cells (hOB) and a transformed
      human osteoblast cell line (MG-63) were measured. Treatment of hOBs with 2 ng/ml
      of TGF-beta 1 resulted in a rapid increase in c-fos mRNA levels as early as 15
      min post-treatment. A maximum (10-fold) increase was observed at 30 min after TGF
      beta treatment followed by a decrease to control values. Similar responses were
      measured whether the cells were rapidly proliferating or quiescent. TGF-beta 1
      induced jun-B mRNA levels more gradually with steady increase initially observed
      at 30 min and a maximum induction measured at 2 h post-TGF-beta treatment. In
      contrast, TGF-beta treatment caused a time dependent decrease in the c-jun mRNA
      levels, an opposite pattern to that of jun-B mRNA. Treatment of hOBs with TGF
      beta 1 in the presence of actinomycin-D abolished TGF-beta 1 induction of c-fos
      mRNA, suggesting that TGF-beta action is mediated via transcription. In the
      presence of cycloheximide, TGF-beta causes super-induction of c-fos mRNA at 30
      min, indicating that the c-fos expression by TGF-beta is independent of new
      protein synthesis. Further, transfection of 3 kb upstream region of jun-B
      promoter linked to a CAT reporter gene into ROS 17/2.8 cells was sufficient to be
      regulated by TGF-beta 1. Interestingly, TGF-beta treatment also increased the
      mRNA levels of TGF-beta 1 itself at 4 h post TGF-beta treatment, with a maximum
      increase observed at 14 h of treatment. TGF-beta 1 treatment for 30 min were
      sufficient to cause a delayed increase in TGF-beta protein secretion within 24 h.
      These data support that TGF-beta has major effects on hOB cell proto-oncogene
      expression and that the nuclear proto-oncogenes respond as rapid, early genes in
      a cascade model of hormone action.

PMID- 7721959
TI  - Temporal variation of c-Fos proto-oncogene expression during osteoblast
      differentiation and osteogenesis in developing rat bone.
AB  - To delineate the implication of c-fos protooncogenic in the osteogenie process,
      we have investigated the temporal pattern of c-fos mRNA expression in fetal and
      neonatal rat bone during intramembranous and endochondral bone formation.
      Northern blot analysis of mRNA extracted from calvaria and femur showed that
      expression of c-fos, Histone H4, and osteocalcin mRNAs followed a temporal
      sequence during bone development. The levels of histone H4 mRNA, a marker of cell
      proliferation, were high at early stages of fetal development of calvaria and
      femur, and decreased until birth. In both the postnatal calvaria and femur, c-fos
      mRNA levels increased transiently at birth and preceded a rise in osteocalcin
      transcripts, a marker of the mature osteoblast phenotype. The immunohistochemical
      analysis showed that c-Fos protein was expressed in osteoprogenitor cells in the
      perichondrium and periosteum, and not in mature osteoblasts which expressed
      markers of differentiated osteoblasts such as type-I collagen, bone sialoprotein,
      and osteocalcin. Thus, the transient c-fos proto-oncogene expression during the
      postnatal life that precedes the osteocalcin expression may be involved in the
      transition from the precursor state to mature osteoblasts. These results suggest
      that c-fos proto-oncogene may play an important role in osteogenesis during rat
      postnatal life.

PMID- 7721960
TI  - Sulfate restriction induces hyposecretion of the adhesion proteoglycan and cell
      hypomotility associated with increased 35SO4(2-) uptake and expression of a band
      3 like protein in the marine sponge, Microciona prolifera.
AB  - Sulfate is an important component relating to normal proteoglycan secretion and
      normal motility in the marine sponge, Microciona prolifera. The following
      alterations were observed in sponge cells when sulfate free artificial sea water
      was used as the suspension medium: 1) impairment of aggregation, 2) loss of cell
      movements, 3) a marked reduction in the secretion of the adhesion proteoglycan
      (AP). Reversal of this effect occurred if sulfate depleted cells were again
      rotated in sulfate containing artificial sea water. Motility and reaggregation of
      sulfate deprived cells could be completely restored by purified AP, but only if
      cells were first pre-conditioned in normal sea water. Comparisons of 35SO4(2-)
      uptake between normal and sulfate deprived cells which had been treated to reduce
      preformed secretions showed a marked increase in 35SO4(2-) uptake and
      incorporation which could be greatly augmented in the presence of Ca2+/Mg2+.
      Excessive retention of AP in sulfate starved cells demonstrated by immunostaining
      suggested that AP secretion and cellular motility may be controlled by a sulfate
      dependent secretogogue or that undersulfated AP itself had developed a secretory
      defect. SDS-PAGE of Triton treated cellular extracts demonstrated a 116 kDa
      35SO4(2-) sulfated band which co-migrated with AP, but only in extracts derived
      from sulfate starved cells. Western blots prepared from such extracts incubated
      in the presence of a monoclonal anti-band 3 antibody demonstrated labelling of a
      single 97 kDa band only in material from sulfate deprived cells. The absence of
      this component in normal cell extracts indicated that this protein may be
      involved in facilitated sulfate transport. This study lends support to a
      heretofore unrecognized role for sulfate in cell motility and secretion.

PMID- 7721961
TI  - Proximal promoter binding protein contributes to developmental, tissue-restricted
      expression of the rat osteocalcin gene.
AB  - Osteocalcin is a 6 kD tissue-specific calcium binding protein associated with the
      bone extracellular matrix. The osteocalcin gene is developmentally expressed in
      postoproliferative rat osteoblasts with regulation at least in part at the
      transcriptional level. Multiple, basal promoter and enhancer elements which
      control transcriptional activity in response to physiological mediators,
      including steroid hormones, have been identified in the modularly organized
      osteocalcin gene promoter. The osteocalcin box (OC box) is a highly conserved
      basal regulatory element residing between nucleotides -99 and -76 of the proximal
      promoter. We recently established by in vivo competition analysis that protein
      interactions at the CCAAT motif, which is the central core of the rat OC box, are
      required for support of basal transcription [Heinrichs et al. J Cell Biochem
      53:240-250, 1993]. In this study, by the combined utilization of electrophoretic
      mobility shift analysis, UV cross linking, and DNA affinity chromatography, we
      have identified a protein that binds to the rat OC box. Results are presented
      that support involvement of the OC box-binding protein in regulating selective
      expression of the osteocalcin gene during differentiation of the rat osteoblast
      phenotype and suggest that this protein is tissue restricted.

PMID- 7721962
TI  - The subject under study was loss.

PMID- 7721963
TI  - "Being with" a patient who is dying.
AB  - Doubting her ability to assume the new manager's role in a specialty unit, the
      author reflects upon her first day of hospital orientation. The monotony of the
      day is interrupted by the admission of a patient with a traumatic burn injury.
      The new manager finds herself perplexed about what to do. Feeling at a loss and
      somewhat confused about her role as a nurse and manager, she delves into her soul
      and realizes that her place on the burn team has nothing to do with the type of
      emergency situation before her. Suddenly, she identifies that her feelings of
      fear and uncertainty are also experienced by people in their new role as
      patients. She recognizes that her place stems from the very essence of being a
      nurse. She wants to care. Basing her actions on her feelings, the nurse is able
      to comfort a man who is dying. She does not want him to feel lonely and afraid
      regardless of his imminent death. Clinically, she knows the team's life-saving
      efforts will be unsuccessful, yet her efforts in caring based on her lived
      experience of being the "newcomer" enable her to accept the challenge of meeting
      the needs of her patient and at the same time regain her confidence.

PMID- 7721964
TI  - Our story.

PMID- 7721965
TI  - Childhood bereavement after the death of a sibling.
AB  - The article describes a study designed to explore the processes of sibling
      bereavement and to compare children's impressions with those of their parents.
      The Institute of Medicine model was used as a sensitizing framework for the
      study. Constant comparative technique was used to analyze data from a pilot study
      of 18 bereaved siblings aged 4 to 23 years. Sadness was the most common reaction
      after sibling death. Mothers were most often cited as being helpful; friends and
      fathers were also helpful. People who were not actively supportive were not
      helpful. Many children described feeling protective of their parents, and several
      children described personal growth.

PMID- 7721966
TI  - Loss of a parent in childhood: attachment and coping in a model of adolescent
      resilience.
AB  - Adolescent resilience after parental death in childhood and its relationship to
      attachment and coping were examined in this cross-sectional correlational study.
      Resilience was operationalized as social competence, global self-worth, and
      health. Sixty-two adolescents were interviewed using self-report instruments.
      Pearson product moment correlations and multiple regression analyses were used to
      test five hypotheses. Three hypotheses were partially supported in that adaptive
      coping was a significant predictor of the measures of resilience. Correlations
      were significant between attachment and coping and between attachment and health.
      All adolescents shared observations about their experiences.

PMID- 7721967
TI  - Strategies of enduring and the suffering of loss: modes of comfort used by a
      resilient survivor.
AB  - In this case study, the narrative of a young mother who survived multiple losses
      and excruciating and prolonged pain in the treatment of burns is explored to
      develop and contrast the concepts of enduring and suffering. Joan survived an
      explosion that resulted in the death of her three children, disfiguring thermal
      injuries, the loss of her husband through divorce, and, as a consequence, the
      loss of her home, church, and community. Strategies of enduring--surviving the
      immediate impact of trauma, the long-term medical treatment and rehabilitation,
      and social adjustment--are described and contrasted with the experience of
      suffering. The article describes how Joan ultimately reformulated an acceptable
      sense of self and of the future. Her capacity to endure pervaded both physical
      and emotional dimensions of healing. Nursing care that did not assist her to
      endure, and therefore increased her suffering, and care that was perceived to be
      comforting, and therefore enhanced her ability to endure and reduced her
      suffering, are described.

PMID- 7721969
TI  - The menopausal transition: change, loss, and adaptation.
AB  - The menopausal transition may be regarded as a developmental stage in the life
      cycle during which women gradually adapt to biologic, social, psychologic, and
      spiritual changes that accompany ovarian decline and menstrual cessation.
      Although the biomedical view stresses atrophic and degenerative changes, a
      developmental and holistic perspective stresses the individuality, totality, and
      complexity of responses to this experience. Sensitive care during the menopausal
      transition may enable women to accept the inevitable changes and losses and
      recognize qualities and capabilities that can unfold. The author is a nurse
      specialist in women's health care who draws from her research and clinical
      practice to provide illustrations for her perspective.

PMID- 7721968
TI  - Looking for guarantees.
AB  - The article attempts to capture some of the author's experience with the
      diagnosis and subsequent treatment of her son's cancer. David was 15 when he was
      diagnosed with Ewing's sarcoma of the left femur. He underwent chemotherapy
      within 3 weeks of the diagnosis, having undergone port insertion, a needle biopsy
      of the tumor, and numerous other diagnostic procedures. After four chemotherapy
      treatments and a series of radiation treatments, David underwent an 8-hour
      operation to reconstruct the left femur. Bank bone was used as well as the fibula
      from his lower leg and iliac crest bone from the same side. David continued to be
      on chemotherapy treatments for just under 2 more years. As a result of this
      experience, the author's priorities, ways of being with clients, relationships
      with family members and friends, and outlook on life have all been affected. She
      has a new appreciation of all that a family goes through when a loved one is in
      crisis and how it affects the entire family and network of friends.

PMID- 7721970
TI  - Women living in paradox: loss and discovery in chronic illness.
AB  - Six women with chronic illness engaged in multiple conversations with the
      investigator to help her understand what it is like to live with chronic illness.
      Phenomenologic writing and reflection were used to analyze the data. The story is
      guided by an integrating theme: Living in paradox circumscribes one's loss while
      enabling one to embrace new discoveries of self in the life world through
      unfolding awareness.

PMID- 7721971
TI  - Finding meaning in caring for elderly relatives: loss and personal growth.
AB  - The literature on family caregiving has focused primarily on caregiver burden and
      demographic characteristics of caregiver groups. Little has been written about
      the existential aspects of caring for an aging relative. The article focuses on
      the meaning of the experience as expressed by family caregivers to elderly
      relatives and the role this meaning plays in enabling the family member to remain
      in the caregiving role. The caregiving passage includes families facing loss,
      identifying turning points, rediscovering a sense of self, and experiencing
      feelings of satisfaction and enhanced self-worth.

PMID- 7721972
TI  - [Angles among main cranial sutures in Japanese].
AB  - To examine a relation of angles among the coronal, sagittal and lambdoid sutures
      to the size of the calvaria as well as to the remains of the metopic suture, 158
      adult Japanese calvae or calottes were observed. The calvae used consisted of
      four groups: group M composed of 74 male calvae without the metopic suture; group
      F, of 41 female calvae without the same suture; group Un, of 27 sex-unknown
      calvae without the same suture; and group Um, of 16 sex-unknown calvae with the
      same suture. The angles among the sutures were measured at both bregma and
      lambda. The size of the calvaria was represented by bistephanic arc and breadth
      (distance between the stephanions), and by parietal sagittal arc and chord
      (distance from the bregma to the lambda). Results obtained were as follows. The
      distances both between the stephanions and from the bregma to the lambda were
      larger in M than in F, though these distances in M, F and Un were much the same
      as those in Um. The bistephanic index (breadth/arc) was higher in Um than in F,
      whereas the sagittal parietal indices (arc/chrod) in M, F and Um were similar to
      one another. Apical angle of the frontal squama was larger in M than in F, and
      was larger in Um than in M and F. However, apical angle of the occipital squama
      showed no difference among M, F and Um.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721973
TI  - [Evaluation of the chemotherapy of a transplantable bladder tumour strain (NM-B
      1) by two anti-cancer drugs in combination with a pressor agent in nude mice].
AB  - The anti-cancer effects of either Cis-diammine (Glycolato) platinum II (CDGP-II),
      a novel platinum derivative, or ifosfamide (IFX) on bladder carcinoma strain NM-B
      1 inoculated in nude mice were examined. These chemotherapeutic agents were
      compared with each other in terms of their inhibitory effect on tumor growth,
      their histology, and the concentration of each agent in the blood, tumor tissue,
      liver and kidneys. (1) The tumor growth was inhibited by CDGP-II in all three
      different dosage groups (p < 0.05), but not by IFX (p > 0.05). These results were
      also confirmed by histological examination. (2) The amount of CDGP-II (30 mg/kg)
      in the tumor tissue increased in a time-dependent manner, while in the blood
      plasma and kidney tissue, it decreased. Total value (TV) and active metabolite
      (AML) of IFX (500 mg/kg) were examined. TV in the tumor tissue decreased in a
      time-dependent manner. AML could not be detected. There was no change of AML in
      the blood plasma, liver, and kidneys. (3) Transmigration of single loading of
      CDGP-II or IFX with Angiotensin II (AT-II) from blood into the tissue was
      examined. CDGP-II in the blood plasma, tumor, liver and kidneys increased in a
      time-dependent manner. After single administration of IFX, TV decreased in the
      blood plasma, tumor, liver and kidneys, while AML increased in the blood and
      kidneys (p < 0.01). (4) The results suggest that CDGP-II may have an anti-tumor
      effect of NM-B-1. However, the effect can not be enhanced under the influence of
      a pressor chemotherapeutic agent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7721974
TI  - Portal and systemic hemodynamic responses to a very low dose of nitroglycerin in
      cirrhotic patients with portal hypertension.
AB  - Portal and systemic hemodynamic responses to a very low dose of nitroglycerin
      were studied in patients with portal hypertension and cirrhosis, and compared
      with those to a high dose of this compound. A 0.15 mg dose of nitroglycerin was
      given sublingually to 10 patients (LDG), and 0.3 mg to another 10 (HDG).
      Hemodynamic measurements were performed by means of hepatic venous and right
      cardiac catheterization before and 5 min after nitroglycerin administration. The
      wedged hepatic venous pressure decreased after dosing by 7.9% (p < 0.01) in LDG,
      and by 15.3% (p < 0.01) in HDG. Hepatic blood flow with ICG did not change in
      either group. In LDG, azygos blood flow remained unchanged, in contrast to a
      significant decrease by 10.1% (p < 0.05) in HDG. Mean arterial pressure fell by
      3.6% (p < 0.05) in LDG and by 18.6% (p < 0.01) in HDG. Cardiac index did not
      change in LDG, but decreased by 11.4% (p < 0.05) in HDG. In both groups, mean
      pulmonary arterial pressure and pulmonary capillary wedge pressure fell
      significantly by the same amount. In HDG, a significant correlation between
      changes in wedged hepatic venous pressure and azygos blood flow (r = 0.70, p <
      0.05) was observed. This suggested that splanchnic vasoconstriction mediated by a
      high-pressure, rather than a low-pressure, baroreceptor reflex was the main
      contributor to a decrease in portal venous blood flow, resulting in a reduction
      in wedged hepatic venous pressure; whereas a slight but significant fall of
      wedged hepatic venous pressure induced by a very low dose of nitroglycerin might
      have been due to venodilatation in the portal system and the hepatic vascular
      bed. These data suggest that, even with a very low dose of nitroglycerin, partial
      improvement of the hepatic circulation can be expected with minimal change in the
      systemic circulation in patients with cirrhosis and portal hypertension.

PMID- 7721975
TI  - [Studies on the classification of clinical stage and histopathological grade of
      gastric cancer, the contribution of clinical findings and clinico-pathological
      changes including immunological responses].
AB  - The data from 329 gastric cancer patients (206 males and 123 females) were
      applied to the following statistical analysis. The stage of gastric cancer
      progress, which was determined by the general rules for the gastric cancer study
      in Japan, the counterpart of the TNM classification was predictable by a multi
      variative mathematical model based on Hayashi's quantification theory which
      allowed to use qualitative variables as well as quantitative ones for the
      calculation using the variables relevant to clinical findings consisted of the
      grade of surgical operability, the grade of histopathological change, positive or
      negative liver metastasis, positive or negative histopathologically detectable
      lymph-node metastasis and so on. The variables relevant to clinical findings
      predicted accurately the stage by the above-cited model and multi-variative
      correlation coefficient (R2) was 0.9475, suggesting that 95% of the values
      predicted by those variables could identical to the observed value of the cancer
      stage. The variables relevant to clinical findings contributed only 29% (R2 =
      0.2902) to the prediction of the histopathological grade. The stage and the
      histopathological grade also were predictable with the multi-variative regressive
      equations using the data of the clinico-pathological examinations which were
      administered on the day before the operation to 239 patients (139 males and 95
      females) of gastric cancer and 82 control surgical patients (50 males and 32
      females). The clinico-pathological indicators consisted of the SI values of Con A
      and PHA, leukocytes' count, lymphocytes' count, serum albumin concentration, B-
      and T-cell numbers. The factors which contributed to the stage, or the
      histopathological grade of gastric cancer were extracted respectively through
      principal component analysis using the respective correlation matrices consisted
      of the variables used for the calculation of the multi-variative regression
      equations in order to predict the stage or histopathological grade. For the male
      patients, the aging factor contributed to both of the stage and the
      histopathological grade. For the female patients, the factor relevant to the
      complication such as infectious diseases and low-nutrition emaciating the patient
      contributed to the cancer stage and the factor relevant to T-lymphocyte function
      contributed to the histopathological grade.

PMID- 7721976
TI  - Branch retinal vein occlusion decreases the potential of the inner retinal layer.
AB  - To identify the affected retinal layer in cases of branch retinal vein occlusion
      (BRVO), we analyzed the scotopic electroretinogram (ERG) and electrooculogram
      (EOG) obtained on the same day in 30 patients with unilateral BRVO. Patients with
      eye diseases other than unilateral BRVO were excluded. A dome-shaped Ganzfeld
      illuminator was used for scotopic ERG stimulation and EOG illumination under
      conventional recording conditions. There was no significant difference in the
      mean values of scotopic ERG variables between the eyes with BRVO and the normal
      eyes, but the EOG light peak and L/D ratio were significantly lower in the eyes
      with BRVO (p < 0.05). However, there was no significant difference between eyes
      with BRVO and normal eyes regarding the dark through value. Since the light rise
      potential is induced by background illumination, the low values for light peak
      and L/D ratio in the eyes with BRVO represent a decrease in the light rise
      potential compared with that of normal eyes. In addition, since the b wave
      amplitude of the ERG was normal in the eyes with BRVO, the scotopic ERG and EOG
      tests suggest that generalized mild hypoxia affects the inner retinal layer of
      the eyes with BRVO.

PMID- 7721977
TI  - [The findings indicate that HSP70 expression is closely related to ischemic brain
      injury, and that HSP70 expression is not related to either breakdown of the blood
      brain barrier or reactive axonal changes].
AB  - The relationship between the 70-kilodalton hear shock protein (HSP70),
      morphological changes in neurons, protein extravasation, and reactive axonal
      changes was evaluated in rats with fluid percussion injuries to the right side of
      the brain. (4.8-5.6 atm, 20 ms). From 1 hour to 2 weeks after injury (or sham
      injury), serial sections of the brains were immunostained with antibodies to
      HSP70, rat IgG, and 68-kilodalton neurofilament. Ischemic changes in neurons in
      the injured cortex were noted in samples taken from 6 to 48 hours after injury,
      and macroscopic hemorrhages were noted in the corpus callosum and external
      capsule. Reactive axonal swelling was observed in the brain stem in samples taken
      from 6 to 48 hours after injury. Immunostaining of HSP70 was positive in the
      injured cortex from 6 hours to 1 week after injury. Maximal immunostaining was
      observed by 48 hours after injury in the injured cortical layers II and III. The
      region of HSP70 expression at 24 and 48 hours postinjury was the same as the
      region of ischemic cell changes. There were discrepancies between the region of
      HSP70 expression and the regions of IgG immunoreactivity and reactive axonal
      changes. These findings indicate that HSP70 expression is closely related to
      ischemic brain injury, and that HSP70 expression is not related to either
      breakdown of the blood-brain barrier or reactive axonal changes.

PMID- 7721978
TI  - [Circadian variation in cardiovascular disease].

PMID- 7721979
TI  - [Fluctuation of heart rate and autonomic nervous system].

PMID- 7721980
TI  - Colocalization of somatostatin, neuropeptide Y, and NADPH-diaphorase in the
      caudate-putamen of the rat.
AB  - Somatostatin, neuropeptide Y, and nicotinamide adenine dinucleotide phosphate
      diaphorase are colocalized within a small population of medium aspiny neurons in
      the caudate-putamen of the rat. The extent of colocalization, however, appears to
      be in dispute. In order to examine the question of colocalization between these
      three neuroactive substances, a series of double-labelling experiments was
      performed. This was accomplished by combining immunocytochemistry for
      somatostatin or neuropeptide Y or enzyme histochemistry for nicotinamide adenine
      dinucleotide phosphate-diaphorase with in situ hybridization for somatostatin
      and/or neuropeptide Y mRNA. The results of such analysis indicate that
      nicotinamide adenine dinucleotide phosphate-diaphorase and somatostatin mRNA are
      100% colocalized throughout the caudate-putamen, except for the area bordering
      the globus pallidus. All neurons that contain neuropeptide Y contain somatostatin
      message. Only 84% of the neurons that contain somatostatin mRNA, however, also
      contain neuropeptide Y. Neurons that contain somatostatin 28 but not neuropeptide
      Y are found throughout the caudate-putamen. These results indicate that the
      somatostatin neuron population in the rat caudate-putamen is not homogeneous.
      Instead, the medium aspiny neuron population is actually composed of several
      subpopulations based on the content of neuroactive substances.

PMID- 7721981
TI  - Development of the catecholamine neurons in human embryos and fetuses, with
      special emphasis on the innervation of the cerebral cortex.
AB  - The cathecholaminergic (CA) systems have been described as appearing early in the
      development of the mammalian central nervous system (CNS), but their exact
      distribution in humans has been studied only following gestational week (g.w.)
      13. Furthermore, it is not known when CA fibers initially penetrate the
      developing cerebral cortex. In this study, the CA cells groups and fibers are
      described in the human central nervous system from 6 to 13 g.w. as revealed with
      immunocytochemical techniques, with antibodies raised against three synthetic
      enzymes of the catecholamine (CA) pathway: tyrosine hydroxylase (TH), dopamine
      beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT). At 6
      g.w., TH-like immunoreactive (TH-IR) cell groups were widespread through the
      caudorostral extension of the CNS corresponding to the different dopaminergic
      mesencephalic and hypothalamic groups. Noradrenergic groups also were labeled in
      the medulla oblongata and in the locus coeruleus as well as in other areas in the
      pons. Additional TH-IR cell groups might represent a transient developmental
      expression of TH similar to that observed in the rat. DBH immunoreactivity
      labeled primarily the noradrenergic pontic cell groups and, to a lesser extent,
      groups located in the medulla oblongata. Rare PNMT-IR neurons were detected in
      the medulla oblongata only at 13 g.w. The main CA bundles described in the adult
      were also observed in human embryos and fetuses. At 6 g.w., TH-IR pathways
      extended caudorostrally within the central tegmental tract and the dorsal
      tegmental bundle, the latter merging with the dopaminergic mesotelencephalic
      pathway giving rise to the medial forebrain bundle in the basal forebrain. At 7-8
      g.w., TH-IR fibers extended to the basal ganglia and the telencephalic wall. The
      first TH-IR and, to a much lesser extent, DBH-IR fibers penetrated the frontal
      lateral cortical anlage through the intermediate zone and sparsely through the
      marginal zone but not through the thin cortical plate. A second stream entered
      the telencephalic anlage frontomedially, ventral to the septal area. At 11 g.w.,
      numerous TH-IR fibers invaded the subplate layer, but they penetrated the
      cortical plate only at 13 g.w. At that time, TH-IR and DBH-IR fibers had reached
      the occipital cortex in a rostrocaudal gradient. The appearance of well-organized
      CA system already in embryonic stages in humans could be of great importance for
      normal shaping of the nervous system as well as for development of cortical
      circuitry.

PMID- 7721982
TI  - Structure and innervation of the sensory organs on the snout of the star-nosed
      mole.
AB  - The star-nosed mole possesses a conspicuous specialization of its snout in the
      form of 22 fleshy appendages that fan out from around the nostrils. These
      appendages are used by the mole to explore its underground environment and are
      repeatedly brought into contact with objects of interest to the mole. This report
      describes the structure, innervation, and distribution of the sensory organs on
      the star of the star-nosed mole and briefly describes the behavioral use of the
      star. Each of the 22 appendages of the star is covered with a continuous array of
      Eimer's organs. These sensory receptors are modifications of the epidermal
      surface that take the form of bulbous papillae. Each Eimer's organ contains a
      column or stack of epidermal cells accompanied by nerve processes that originate
      from myelinated fibers in the underlying dermis. These neural processes travel
      through the cell column and form terminal swellings just below the outer layer of
      keratinized epidermis. Each Eimer's organ also contains a single Merkel cell
      neurite complex within the cell column and a single lamellated corpuscle
      immediately below the cell column in the connective tissue of the dermis. There
      are approximately 30,000 Eimer's organs on the snout of this mammal, making this
      structure perhaps the most sensitive tactile organ yet discovered for its size.
      The segregation of these organs to individual appendages, not unlike the fingers
      of primates, affords an intriguing model for the study of somatosensory systems
      in mammals.

PMID- 7721983
TI  - Organization of the somatosensory cortex of the star-nosed mole.
AB  - The nose of the star-nosed mole consists of a star-like array of 22 fleshy
      appendages that radiate from the nostrils and are moved about to explore the
      environment. The surface of each appendage, or ray, is densely packed with
      bulbous receptor organs (Eimer's organs) that are highly responsive to tactile
      stimulation. Here, we report that these rays have corresponding morphological
      specializations in somatosensory cortex. Using a stain for the metabolic enzyme,
      cytochrome oxidase (CO), to reveal subdivisions of cortex, we disclosed a complex
      pattern of CO-dense stripes or bands separated by sharp lines or septa of low CO
      staining. Multiunit microelectrode recordings of neural activity evoked by light
      tactile stimuli in somatosensory cortex of anesthetized moles allowed us to mark
      some of the bands and other CO-dark regions with small electrolytic lesions and
      later relate recording results to the CO pattern. The results suggest that the
      primary somatosensory cortex, S1, has an unusual ventrolateral location and
      orientation with representations of mouth, nose rays, facial vibrissae, forepaw,
      and trunk in a rostrocaudal sequence. Within this presumptive S1, the 11 rays of
      the contralateral nose are represented as a rostral-to-caudal cortical pinwheel
      of 11 stripes. Cortex ventral to the primary set of stripes contains a second
      rostrocaudal representation of the rays as a mirror image of the first. This
      second set of stripes may be part of the second somatosensory area, S2. A third
      pattern of CO stripes appears to merge partially with caudal stripes of the first
      two patterns, so that a full pattern of 11 stripes is not obvious. This
      representation may correspond to the ventral somatosensory area, VS, of other
      mammals. An extensive area of cortex separated from the nose by a large septum
      was responsive to stimulation of the forelimb. Auditory cortex is unusually
      caudal in this mole, and the presumptive primary visual area is relatively small.
      These specializations of somatosensory cortex in star-nosed moles may be more
      patent examples of the consequences of more general factors in brain development.
      The observations are consistent with the general rule that the terminations of
      sensory projections with discorrelated activity segregate.

PMID- 7721984
TI  - The efferent projections of the periaqueductal gray in the rat: a Phaseolus
      vulgaris-leucoagglutinin study. I. Ascending projections.
AB  - This study has examined the ascending projections of the periaqueductal gray in
      the rat. Injections of Phaseolus vulgaris-leucoagglutinin were placed in the
      dorsolateral or ventrolateral subregions, at rostral or caudal sites. From either
      region, fibers ascended via two bundles. The periventricular bundle ascended in
      the periaqueductal and periventricular gray matter. At the posterior commissure
      level, this bundle divided into a dorsal component that terminated in the
      intralaminar and midline thalamic nuclei, and a ventral component that supplied
      the hypothalamus. The ventral bundle formed in the deep mesencephalic reticular
      formation and supplied the ventral tegmental area, substantia nigra pars
      compacta, and the retrorubral field. The remaining fibers were incorporated into
      the medial forebrain bundle. These supplied the lateral hypothalamus and
      forebrain structures, including the preoptic area, the nuclei of the diagonal
      band, and the lateral division of the bed nucleus of the stria terminalis. The
      dorsolateral subregion preferentially innervated the centrolateral and
      paraventricular thalamic nuclei and the anterior hypothalamic area. The
      ventrolateral subregion preferentially innervated the parafascicular and central
      medial thalamic nuclei, the lateral hypothalamic area, and the lateral division
      of the bed nucleus of the stria terminalis. Although the dorsolateral and
      ventrolateral subregions gave rise to differential projections, the projections
      from both the rostral and caudal parts of either subregion were similar. This
      suggests that the dorsolateral and ventrolateral subregions are organized into
      longitudinal columns that extend throughout the length of the periaqueductal
      gray. These columns may correspond to those demonstrated in recent physiological
      studies.

PMID- 7721985
TI  - The efferent projections of the periaqueductal gray in the rat: a Phaseolus
      vulgaris-leucoagglutinin study. II. Descending projections.
AB  - The descending projections of the periaqueductal gray (PAG) have been studied in
      the rat using the anterograde tracer Phaseolus vulgaris-leucoagglutinin. The
      tracer was injected into the dorsolateral or ventrolateral subdivisions of the
      PAG at rostral or caudal sites. It was found that the patterns of the descending
      projections of the rostral and caudal parts of the dorsolateral PAG were the same
      and that the patterns of the descending projections of the rostral and caudal
      parts of the ventrolateral PAG were the same. However, the patterns of
      projections of the dorsolateral and ventrolateral PAG subregions were
      substantially different. These results suggest that the dorsolateral and
      ventrolateral parts of the PAG are organized into longitudinal columns that
      extend throughout the length of the PAG. The axons of PAG neurons descended
      through the pons and medulla via two routes. A small fiber bundle was present in
      the periaqueductal gray and in the periventricular area. This bundle distributed
      fibers and terminals locally within the periaqueductal gray and in the locus
      coeruleus and Barrington's nucleus. A larger bundle had a diffuse arrangement in
      the pontine reticular formation, however, and it had a more restricted
      distribution in the medulla, where it occupied a position dorsolateral to the
      pyramid. This bundle supplied structures in the pontine and medullary tegmentum.
      The dorsolateral column preferentially supplied the locus coeruleus,
      subcoeruleus, the gigantocellular nucleus pars alpha, the rostral part of the
      paragigantocellular nucleus, and the region of the A5 noradrenergic cell group.
      The ventrolateral column preferentially supplied the nucleus raphe magnus, the
      caudal part of the lateral paragigantocellular nucleus, and the
      rostroventrolateral reticular nucleus.

PMID- 7721986
TI  - Development of the hippocamposeptal projection in the rat.
AB  - We analyzed the development of the hippocamposeptal projection and the morphology
      of the neurons giving rise to this projection. The fluorescent tracer Dil was
      injected into the septal region or the hippocampus in fixed brains of embryonic
      and early postnatal rats. Anterogradely labeled hippocampal axons first reached
      the septal region at E16. They ran along the midline of the brain, thereby
      approaching the medial septum. Axons to the lateral septum were first observed
      around E18/19. The lateral septum is partly innervated by collaterals of axons
      that travel to the medial septum. The projection to the lateral septal nuclei
      becomes more massive during early postnatal stages, whereas that to the medial
      septum becomes smaller. Cells in the medial septum retrogradely labeled by
      injection into the hippocampus were first observed at E18. Thus, the
      hippocamposeptal projection is established earlier than the septohippocampal
      projection. The first hippocampal projection neurons are nonpyramidal neurons
      that appear to pioneer the pathway to the septum. Pyramidal cell axons follow
      this first cohort of axons into the medial septum. Pyramidal cells could be
      retrogradely labeled from the medial septum during the perinatal period but then
      diminished in number. At P10, only nonpyramidal cells were labeled by medial
      septal injections. This indicates that the pyramidal component of this projection
      is transient and is removed shortly after birth. However, as is known from other
      studies, hippocampal pyramidal cells give rise to a powerful projection to the
      lateral septum in adult animals. Our results show that there is a considerable
      remodeling of the projection from the hippocampus to the septum during
      ontogenetic development.

PMID- 7721987
TI  - Seven protein tyrosine phosphatases are differentially expressed in the
      developing rat brain.
AB  - Regulation of protein function through tyrosine phosphorylation is critical in
      the control of many developmental processes, such as cellular proliferation and
      differentiation. Growing evidence suggests that tyrosine phosphorylation also
      regulates key events in neural development. Although a large body of data has
      demonstrated that protein tyrosine kinases play an important role in neural
      development, much less is known about their counterparts, protein tyrosine
      phosphatases (PTPases). Using polymerase chain reaction (PCR) with degenerate
      primers and a neonatal rat cortex cDNA library, we have identified seven PTPases
      expressed in the developing rat brain. Four of these are transmembrane PTPases:
      LAR, LRP, RPTP gamma, and CPTP1. Three are nonreceptor PTPases: PTP-1, P19-PTP,
      and SHP. Northern hybridization analysis demonstrates that only CPTP1 is
      preferentially expressed in neural tissues, whereas the others are found
      abundantly in nonneural tissues as well as in the brain. Within the embryonic and
      early postnatal brain, the seven PTPases have overlapping, yet unique,
      distributions. For example, LAR mRNA is highly expressed by both proliferating
      and postmitotic cells in the cerebral cortex at embryonic day 17 and in all
      layers of the cortex at postnatal day 4. In contrast, RPTP gamma mRNA is
      expressed by postmitotic neurons in the embryo and predominantly by neurons in
      the superficial layers of the postnatal cortex. Several of the PTPases examined
      here are expressed at very high levels in the embryonic cortical plate and
      postnatal neocortex, including the subplate and subventricular zone. The spatial
      and temporal regulation of PTPase gene expression suggests that these PTPases
      have important roles in signal transduction during early neuronal differentiation
      and neural development.

PMID- 7721988
TI  - Neurofilament protein defines regional patterns of cortical organization in the
      macaque monkey visual system: a quantitative immunohistochemical analysis.
AB  - Visual function in monkeys is subserved at the cortical level by a large number
      of areas defined by their specific physiological properties and connectivity
      patterns. For most of these cortical fields, a precise index of their degree of
      anatomical specialization has not yet been defined, although many regional
      patterns have been described using Nissl or myelin stains. In the present study,
      an attempt has been made to elucidate the regional characteristics, and to
      varying degrees boundaries, of several visual cortical areas in the macaque
      monkey using an antibody to neurofilament protein (SMI32). This antibody labels a
      subset of pyramidal neurons with highly specific regional and laminar
      distribution patterns in the cerebral cortex. Based on the staining patterns and
      regional quantitative analysis, as many as 28 cortical fields were reliably
      identified. Each field had a homogeneous distribution of labeled neurons, except
      area V1, where increases in layer IVB cell and in Meynert cell counts paralleled
      the increase in the degree of eccentricity in the visual field representation.
      Within the occipitotemporal pathway, areas V3 and V4 and fields in the inferior
      temporal cortex were characterized by a distinct population of neurofilament-rich
      neurons in layers II-IIIa, whereas areas located in the parietal cortex and part
      of the occipitoparietal pathway had a consistent population of large labeled
      neurons in layer Va. The mediotemporal areas MT and MST displayed a distinct
      population of densely labeled neurons in layer VI. Quantitative analysis of the
      laminar distribution of the labeled neurons demonstrated that the visual cortical
      areas could be grouped in four hierarchical levels based on the ratio of neuron
      counts between infragranular and supragranular layers, with the first (areas V1,
      V2, V3, and V3A) and third (temporal and parietal regions) levels characterized
      by low ratios and the second (areas MT, MST, and V4) and fourth (frontal regions)
      levels characterized by high to very high ratios. Such density trends may
      correspond to differential representation of corticocortically (and
      corticosubcortically) projecting neurons at several functional steps in the
      integration of the visual stimuli. In this context, it is possible that
      neurofilament protein is crucial for the unique capacity of certain subsets of
      neurons to perform the highly precise mapping functions of the monkey visual
      system.

PMID- 7721989
TI  - Synaptic distribution of afferents from reticular nucleus in ventroposterior
      nucleus of cat thalamus.
AB  - This study was aimed at determining the synaptic circuitry that contributes to
      the alterations in thalamic function that accompany changes in behavioral states.
      The somatosensory sector of the thalamic reticular nucleus (RTN) was identified
      by microelectrode recording in cats and injected with Phaseolus vulgaris
      leucoagglutinin (PHA-L). The axons of labeled RTN cells gave rise to collaterals
      within the RTN and continued into the dorsal thalamus where they terminated
      predominately in the ventral posterior lateral nucleus (VPL). After small
      injections in the upper limb representation of RTN, most labeled terminations in
      VPL were confined to its medial part, suggesting the presence of a topographic
      organization in the projection. Terminations were concentrated in localized,
      focal aggregations of boutons. Combined electron microscopic immunocytochemistry,
      using immunogold labeling for gamma-aminobutyric acid (GABA), showed that the PHA
      L labeled boutons were GABA-positive terminals that ended in symmetrical
      synapses. Eighty-two percent of these synapses were on dendrites of relay
      neurons, 8.5% on dendrites of interneurons, and 9.3% on somata. The terminals of
      RTN axons form the majority of axon terminals ending in symmetrical synapses in
      VPL. Their concentration on relay neurons probably underlies the capacity of the
      RTN projection to reduce background activity of VPL relay neurons in the awake
      state and to maintain oscillatory behavior of these neurons in drowsiness and
      early phases of sleep.

PMID- 7721990
TI  - Host primary olfactory axons make synaptic contacts in a transplanted olfactory
      bulb.
AB  - Previous light microscopic studies have shown that host olfactory neurons are
      able to grow into a transplanted fetal olfactory bulb, and behavioral studies
      have shown that animals with transplanted olfactory bulbs recover functional
      olfactory abilities. We examined the olfactory bulb transplant at the
      ultrastructural level to determine whether synaptic contacts are reestablished
      between host olfactory neurons and donor olfactory bulb. Mature rats that, as
      neonates, had received embryonic olfactory bulb transplants following olfactory
      bulb removal were studied. An antibody specific for olfactory marker protein was
      used to identify the primary olfactory neurons; it was bound by a gold-conjugated
      secondary antibody for visualization. To preserve the antigenicity of the
      olfactory marker protein for immunolabeling, Lowicryl K4M hydrophilic resin was
      used. Synaptic contacts were unmistakable between labeled axons of host olfactory
      neurons and unlabeled processes within glomerulus-like areas of the transplanted
      olfactory bulb. The surrounding neuropil contained other elements similar to
      those found in normal tissue, including synaptic contacts between unlabeled
      profiles. We clearly show that the transplanted olfactory bulb exhibits
      sufficient plasticity to form an array of normal synaptic contacts, including the
      contacts from host primary olfactory neurons.

PMID- 7721991
TI  - Cardiovascular responses to electrical stimulation of the bed nucleus of the
      stria terminalis.
AB  - To determine whether the influence of the bed nucleus of the stria terminalis
      (BST) on cardiovascular function can be localized to specific cytoarchitectural
      areas within the BST, urethane (1.3 g/kg)-anesthetized male Sprague-Dawley rats
      were probed for cardiovascular reactive sites. Electrical stimuli (50 microA, 50
      Hz, and a 0.5 ms pulse duration), delivered through stereotaxically placed glass
      semimicroelectrodes, were localized to the BST. Sham-stimulated animals served as
      controls. Stimulation sites were correlated with cytoarchitecturally distinct
      areas within the BST, and changes in mean arterial pressure (MAP) were subjected
      to statistical analysis. Systematically probing the BST for cardiovascular
      reactive sites showed a correlation between evoked responses and distinct
      cytoarchitectural areas. Stimulation of the medial BST produced increases in MAP;
      stimulation of the lateral aspect of the BST produced decreases in MAP. Both
      pressor and depressor responses were evoked from the area ventral to the anterior
      commissure. Pressor responses were elicited from the area immediately ventral to
      the anterior commissure, and depressor responses followed stimulation of an area
      more ventral. All subnuclei showed corroborating cardiovascular responses to 20
      30 nl microinjection of sodium glutamate. Taken together, these data provide
      substantial evidence to indicate that the BST, particularly at more rostral
      areas, consists of a medial pressor area, a lateral depressor area, and a ventral
      area with both pressor and depressor zones.

PMID- 7721992
TI  - Expression patterns and deprivation effects on GABAA receptor subunit and GAD
      mRNAs in monkey lateral geniculate nucleus.
AB  - The expression and regulation of seven GABAA receptor subunit gene transcripts
      were examined in the adult monkey lateral geniculate nucleus. In situ
      hybridization histochemistry was used to localize mRNAs of the genes encoding
      monkey-specific alpha 1, alpha 2, alpha 4, alpha 5, beta 1, beta 2, and gamma 2
      subunits. The highest levels of expression in the nucleus were for alpha 1, beta
      2, and gamma 2 subunit transcripts. The levels were substantially higher in the
      magnocellular than in the parvocellular layers. Alpha-2, alpha 4, alpha 5, and
      beta 1 subunit mRNAs were expressed at much lower levels, and magno- and
      parvocellular layers had approximately equal levels of expression. Following 4-
      or 21-day periods of monocular deprivation induced by intravitreal injections of
      tetrodotoxin, levels of the alpha 1, alpha 2, alpha 4, alpha 5, beta 1, and beta
      2 mRNAs were decreased in the deprived geniculate laminae. Adjacent sections
      hybridized with probes specific for 67-kDa glutamic acid decarboxylase (GAD) mRNA
      also showed decreased levels of expression in deprived laminae after the 21-day
      deprivation period. Levels of gamma 2 receptor subunit mRNA were unaffected by
      monocular deprivation. In our previous studies, a clearly significant
      downregulation is observed for this subunit transcript in the visual cortex of
      monkeys deprived for equivalent times. The differential expression and responses
      to deprivation in the lateral geniculate nucleus suggest region-specific
      regulation of GABAA receptor subunit genes.

PMID- 7721993
TI  - Barrelfield of the prenatally X-irradiated rat somatosensory cortex: a
      histochemical and electrophysiological study.
AB  - The effect of prenatal X-irradiation on the vibrissal cortical barrelfield of the
      brain of rats exposed to 200 R on the embryonic day 17 was studied
      morphologically and electrophysiologically. Cytoarchitectural barrels fail to
      appear in adult rats that have been subjected to this in utero treatment.
      However, sections cut in a plane tangential to the vibrissal cortex and examined
      for cytochrome oxidase (CO), a mitochondrial enzyme, contained a matrix of
      patterned CO activity which, albeit smaller and weaker in intensity, is similar
      to CO barrels in normal controls. Current source density analysis of cortical
      field potentials indicated that, as in the normal cortex, the earliest sink
      following peripheral stimulation appears in association with this high CO
      activity. These results suggest that the specific vibrissal thalamocortical
      pathway sets up an excitatory synaptic activity in the cortex of the irradiated
      animal. Efficacy of this route in eliciting postsynaptic spikes in the cortical
      output neurons was confirmed by recording extracellular spike responses to
      vibrissa displacements from layer Vb pyramidal neurons that were then injected
      intracellularly with horseradish peroxidase for later anatomical identification.

PMID- 7721994
TI  - Crayfish brain interneurons that converge with serotonin giant cells in accessory
      lobe glomeruli.
AB  - Freshwater crayfish have well-developed olfactory systems with an array of
      receptors that project exclusively to areas in the brain that are functionally
      specialized for the processing of odors. The accessory lobes are large bilateral
      areas of neuropil that are anatomically associated with the olfactory lobes. The
      accessory lobes receive no primary afferents and do not contain the endings of
      motor efferents; thus, their role in olfaction is still obscure. Intracellular
      dye filling of interneurons in the deutocerebral commissure in the crayfish brain
      has shown that they end bilaterally in glomeruli in the accessory lobes, have
      cell somata in a dorsal cluster medial to the olfactory lobes, and have
      unilateral projections to the deutocerebral commissure neuropil. Each
      deutocerebral commissure interneuron has only 6 to 15 output glomeruli in each
      accessory lobe and does not share glomeruli with other deutocerebral commissure
      interneurons. The deutocerebral commissure interneurons converge with the dorsal
      giant serotonin neurons in the accessory lobe glomeruli. Deutocerebral commissure
      interneurons can be separated into classes according to their projections to the
      protocerebrum, central body, and deutocerebrum. Physiological responses of the
      deutocerebral commissure interneurons following photic stimulation of the eyes
      and electrical stimulation of the second antennae lead to the conclusion that the
      deutocerebral commissure represents an input to the accessory lobes from the
      protocerebral neuropils and that visual and tactile inputs are included in the
      processing performed in the accessory lobes.

PMID- 7721995
TI  - Origins of serotonin-like immunoreactivity in the optic tectum of Rana pipiens.
AB  - We have previously identified a population of serotonin-like immunoreactive (5-HT
      ir) retinal ganglion cells in Rana pipiens. In this study, we examined serotonin
      like immunoreactivity (5-HTLI) in a probable target of those cells, the optic
      tectum. We observed both 5-HT-ir fibers and cell bodies in this structure. 5-HT
      ir cells were located in the cellular layers of the tectum, layers 2, 4, and 6,
      and scattered in its superficial layers. 5-HT-ir fibers in the tectum displayed a
      laminated organization and were located in tectal layers 3, 5, 6, 7, and 9.
      Retrograde labelling experiments showed that 5-HT-ir retinal ganglion cells
      projected to the optic tectum. However, these experiments also demonstrated that
      serotonergic neurons in the midbrain tegmentum, the nucleus isthmi, and the
      medulla did so as well. 5-HT-ir fibers seen in lamina A of layer 9 were very much
      reduced in density in animals in which the optic nerve had been lesioned for 3-6
      months. Immunoreactive fibers in lamina B of layer 9 were not affected by the
      lesion. Our results suggest that 5-HT-ir fibers in lamina A of layer 9 are mainly
      of retinal origin, whereas those in lamina B originate from other brain areas.
      The 5-HT-ir tectal cells located in the cellular layers probably contribute the 5
      HT-ir fibers seen in layers 3, 5, 6, and 7.

PMID- 7721996
TI  - Sensory neuron development revealed by taurine immunocytochemistry in the
      honeybee.
AB  - The formation of ommatidia in the compound eyes and sensilla on the antennae of
      the honeybee was followed and the development of their sensory neurons was traced
      using an antiserum against taurine as a marker. Taurine-like immunoreactivity
      (Tau-IR) is expressed in sensory neurons of several modalities, namely visual,
      olfactory, gustatory, and mechanosensory. Staining intensity is very high in the
      larva and in the first half of the pupal stage and gradually decreases towards
      the end of metamorphosis. In the photoreceptor cells of the compound eyes, Tau-IR
      can be detected from the fifth larval instar onwards, prior to differentiation of
      other components of the ommatidium. Already in the midstage larvae, when the
      antennal primordia of the adult still lie within the peripodial cavity, a few
      presumably mechanosensory neurons are labelled in the pedicellus of the
      developing antenna. The majority of the antennal sensory neurons which are
      located on the flagellum start to exhibit Tau-IR upon pupation, long before any
      cuticular specializations such as sensory hairs or plates are detectable. All
      known types of antennal sensilla were identified and it could be shown that all
      of them are innervated by Tau-IR sensory neurons. Thus, taurine
      immunocytochemistry can be applied as a useful label for developing sensory
      neurons. Functional implications of taurine during development are discussed.

PMID- 7721997
TI  - Physiological regulation of peptide messenger RNA colocalization in rat
      hypothalamic paraventricular medial parvicellular neurons.
AB  - In the present study, we used subcutaneous polyethylene glycol injections to show
      that a physiologically relevant stimulus, hypovolemia, will selectively increase
      the expression of neuropeptide genes in a restricted population of parvicellular
      corticotropin-releasing hormone-containing neurons in the hypothalamic
      paraventricular nucleus. Our results show that a large reduction in extracellular
      fluid maintained over approximately 20 hours is associated with a significant
      increase in the level of corticotropin-releasing hormone mRNA in the medial
      parvicellular division of the paraventricular nucleus. Additionally, there are
      concomitant increases in cellular levels of both neurotensin/neuromedin N and
      proenkephalin mRNAs. Our colocalization results show that the increases in
      neurotensin/neuromedin N and proenkephalin mRNAs after polyethylene glycol
      injection occur to a significant degree in cells that also contain corticotropin
      releasing hormone mRNA. Furthermore, significant numbers of cells containing
      proenkephalin mRNA also contain neurotensin/neuromedin N mRNA, raising the
      possibility that some neurons have increased levels of all three mRNAs. Finally,
      in the medial parvicellular division of the paraventricular nucleus, the number
      of identified corticotropin-releasing hormone neurons also containing vasopressin
      mRNA is very low in control animals and is not increased by polyethylene glycol
      injections, suggesting that, within this period, activation of the vasopressin
      gene may not be a critical event in the neuroendocrine response of corticotropin
      releasing hormone neurosecretory neurons to extracellular dehydration. Considered
      together with the effects of adrenalectomy on peptide colocalization, our results
      suggest the existence of several phenotypically distinct sets of neurons within
      the medial parvicellular division of the paraventricular nucleus, each
      characterized by its ability to regulate the expression of neuropeptide genes in
      a stimulus-specific manner.

PMID- 7721998
TI  - Hippocampal mossy fiber sprouting and synapse formation after status epilepticus
      in rats: visualization after retrograde transport of biocytin.
AB  - In complex partial epilepsy and in animal models of epilepsy, hippocampal mossy
      fibers appear to develop recurrent collaterals that invade the dentate molecular
      layer. Mossy fiber collaterals have been proposed to subserve recurrent
      excitation by forming granule cell-granule cell synapses. This hypothesis was
      tested by visualizing dentate granule cells and their mossy fibers after terminal
      uptake and retrograde transport of biocytin. Labeling studies were performed with
      transverse slices of the caudal rat hippocampal formation prepared 2.6-70.0 weeks
      after pilocarpine-induced or kainic acid-induced status epilepticus. Light
      microscopy demonstrated the progressive growth of recurrent mossy fibers into the
      molecular layer; the densest innervation was observed in slices from pilocarpine
      treated rats that had survived 10 weeks or longer after status epilepticus. Thin
      mossy fiber collaterals originated predominantly from deep within the hilar
      region, crossed the granule cell body layer, and formed an axonal plexus oriented
      parallel to the cell body layer within the inner one-third of the molecular
      layer. When sprouting was most robust, some recurrent mossy fibers at the apex of
      the dentate gyrus reached the outer two-thirds of the molecular layer. The
      distribution and density of mossy fiber-like Timm staining correlated with the
      biocytin labeling. When viewed with the electron microscope, the inner one-third
      of the dentate molecular layer contained numerous mossy fiber boutons. In some
      instances, biocytin-labeled mossy fiber boutons were engaged in synaptic contact
      with biocytin-labeled granule cell dendrites. Granule cell dendrites did not
      develop large complex spines ("thorny excrescences") at the site of synapse
      formation, and they did not appear to have been permanently damaged by seizure
      activity. These results establish the validity of Timm staining as a marker for
      mossy fiber sprouting and support the view that status epilepticus provokes the
      formation of a novel recurrent excitatory circuit in the dentate gyrus.
      Retrograde labeling with biocytin showed that the recurrent mossy fiber
      projection often occupies a considerably greater fraction of the dendritic region
      than previous studies had suggested.

PMID- 7721999
TI  - Morphology of ganglion cells in the neotenous tiger salamander retina.
AB  - The morphology of retinal ganglion cells in the neotenous tiger salamander
      (Ambystoma tigrinum) was analyzed with the aid of morphometric techniques to
      determine the diversity of cell types and to evaluate the widely held notion that
      this form of Ambystoma has a simple retina, with little variance among its cell
      morphologies. Single-cell staining was achieved through retrograde labeling with
      horseradish peroxidase injected around the optic nerve sheath followed by a
      period of several days before tissue processing; 83 well-labelled cells with
      axons were studied in detail with light microscopy and a computer-aided
      reconstruction system. Five different morphological cell classes were devised
      based on broad morphometric criteria such as the dendritic area of influence; the
      number, length, and complexity of dendritic branches; and the amount of overlap
      between neighboring dendrites. These classes included small simple, small
      complex, medium simple, medium complex, and large cells. In addition, a class of
      cells with numerous varicosities among the dendrites was separately analyzed.
      These swellings did not stain for catecholamines. Based on optical determinations
      of the dendritic sublamination pattern within the inner plexiform layer, presumed
      On-Off cells are present in all subclasses, whereas On cells predominate in the
      smaller cell groups. Presumed Off cells are well represented in the large field
      units, although the small total number of cells in this latter class leads to
      uncertainty regarding the significance of this observation. The diversity of
      ganglion cell morphology revealed in the present study argues against the
      assumption that the neotenous tiger salamander has a simple retina, with a
      relatively invariant set of ganglion cells. On the contrary, it appears that this
      aquatic form shows morphological diversity in the retinal ganglion cell
      population rivaling that reported for other vertebrates, including mammals. A
      functional role for the different cell classes is briefly considered.

PMID- 7722000
TI  - Sex differences in the number of synaptic junctions in the binocular area of the
      rat visual cortex.
AB  - We had found that the binocular area of the visual cortex is larger in volume and
      has more neurons in male than in female rats. The present study examined whether
      the number of synaptic junctions in this area is sexually dimorphic. Ten
      littermate pairs of 90-day-old (socially housed) Long-Evans hooded rats were
      used. Synaptic junctions were counted and their lengths were measured on electron
      micrographs taken from layers II-III of the binocular visual cortex. There were
      no sex differences in the numerical density of synaptic junctions, the number of
      synaptic junctions per neuron, or the length of synaptic junctions within any
      synaptic category or of all synapses combined. Sex differences were found in the
      total number of synaptic junctions and in several categories (asymmetric
      synapses, spine synapses, asymmetric spine synapses): male rats had more synaptic
      junctions than female rats because of the larger volume of layers II-III in the
      binocular area of male rats. These data indicate that neurons in the binocular
      visual cortex of both male and female rats receive a characteristic number of
      synaptic junctions, but the greater number of neurons in the binocular area of
      male rats results in more synaptic junctions in the area.

PMID- 7722001
TI  - Afferent connections of the medial frontal cortex of the rat. II. Cortical and
      subcortical afferents.
AB  - In order to compare the frontal cortex of rat and macaque monkey, cortical and
      subcortical afferents to subdivisions of the medial frontal cortex (MFC) in the
      rat were analyzed with fluorescent retrograde tracers. In addition to afferent
      inputs common to the whole MFC, each subdivision of the MFC has a specific
      pattern of afferent connections. The dorsally situated precentral medial area
      (PrCm) was the only area to receive inputs from the somatosensory cortex. The
      specific pattern of afferents common to the ventrally situated prelimbic (PL) and
      infralimbic (IL) areas included projections from the agranular insular cortex,
      the entorhinal and piriform cortices, the CA1-CA2 fields of the hippocampus, the
      subiculum, the endopiriform nucleus, the amygdalopiriform transition, the
      amygdalohippocampal area, the lateral tegmentum, and the parabrachial nucleus. In
      all these structures, the number of retrogradely labeled cells was larger when
      the injection site was located in area IL. The dorsal part of the anterior
      cingulate area (ACd) seemed to be connectionally intermediate between the
      adjacent areas PrCm and PL; it receives neither the somatosensory inputs
      characteristic of area PrCm nor the afferents characteristic of areas PL and IL,
      with the exception of the afferents from the caudal part of the retrosplenial
      cortex. A comparison of the pattern of afferent and efferent connections of the
      rat MFC with the pattern of macaque prefrontal cortex suggests that PrCm and ACd
      areas share some properties with the macaque premotor cortex, whereas PL and IL
      areas may have characteristics in common with the cingulate or with medial areas
      24, 25, and 32 and with orbital areas 12, 13, and 14 of macaques.

PMID- 7722002
TI  - Expression of chondroitin sulfate and keratan sulfate proteoglycans in the path
      of growing retinal axons in the developing chick.
AB  - Previous investigations have identified proteoglycans in the central nervous
      system during development and have implicated some proteoglycans as axon guidance
      molecules that act by inhibiting axon extension. The present study investigated
      the pattern of immunoreactivity for several glycosaminoglycans common to certain
      proteoglycans relative to growing retinal axons in the developing chick visual
      system and in retinal explant cultures. Immunostaining for chondroitin-6-sulfate,
      chondroitin-4-sulfate, and keratan sulfate was observed to colocalize with
      retinal axons throughout the retinofugal pathway during the entire period of
      retinal axon growth. The proteoglycan form of collagen IX, however, was only
      observed in the retina, primarily peripheral to the areas with actively growing
      axons. The pattern of immunostaining for chondroitin sulfate in tissue sections
      suggested that the retinal axons might be a source for some of the chondroitin
      sulfate immunostaining in the developing visual pathway. This was confirmed in
      that chondroitin sulfate immunostaining was also observed on neurites emanating
      from cultured retinal explants. These findings indicate that retinal axons grow
      in the presence of chondroitin sulfate and keratan sulfate proteoglycans and that
      these proteoglycans in the developing chick visual pathway have functions other
      than to inhibit axon growth.

PMID- 7722003
TI  - Afferent reorganisation within the superior olivary complex of the gerbil:
      development and induction by neonatal, unilateral cochlear removal.
AB  - Cochlear removal in young animals has been shown to produce a variety of
      degenerative and generative effects within the auditory brainstem. A primary
      target for axons of neurons in the anteroventral cochlear nucleus (AVCN) is the
      superior olivary complex (SOC). Following unilateral cochlear removal in neonatal
      gerbils, AVCN neurons on the side of the removal die, and axons deriving from the
      AVCN on the unlesioned side produce new endings that innervate previously
      inappropriate target zones within the ipsilateral medial nucleus of the trapezoid
      body, both medial superior olives, and the contralateral lateral superior olive.
      In this study, we have used the anterograde transport of DiI and HRP from the
      AVCN to relate the formation of these endings to the time course of normal
      development in the gerbil brainstem. We have also examined the effects of
      cochlear removal at different ages, and survival to various ages after the
      removal, to define the time course for these generative phenomena. The results
      show that, while the major projection pathways from the AVCN to the SOC are in
      place at the time of birth, further and subtle development of AVCN terminal
      arbors occurs during the first postnatal week. This overlaps with the time during
      which cochlear removal produces the formation of exuberant afferents to the SOC
      from the intact AVCN. The exuberant afferents form through axon sprouting rather
      than through a suppression of normal, developmental regression. They appear to
      innervate tonotopically appropriate target regions within the SOC. The formation
      of the novel afferents begins within 3 days of the removal and appears to be
      complete within a further 5-7 days. By postnatal day (P) 10, both the normal
      development of the AVCN to SOC projection and the potential for alteration of
      that projection by removal of the contralateral cochlea appear to be over. These
      results suggest that the potential for forming novel projections in the gerbil
      auditory brainstem is lost before the onset of functional hearing (at P12) and
      is, therefore, unlikely to result from changes in auditory experience.

PMID- 7722004
TI  - Localization of the heptapeptide GFSKLYFamide in the sea cucumber Holothuria
      glaberrima (Echinodermata): a light and electron microscopic study.
AB  - Two peptides, Gly-Phe-Ser-Lys-Leu-Tyr-Phe-NH2 (GFSKLYFamide) and Ser-Gly-Tyr-Ser
      Val-Leu-Tyr-Phe-NH2 (SGYSVLYFamide), recently isolated from the sea cucumber
      Holothuria glaberrima [Diaz-Miranda et al. (1992) Biol. Bull. 182:241-247]
      represent the first neuropeptides isolated from holothurians. Using an antibody
      against GFSKLYFa, we describe here the localization and distribution pattern of
      GFSKLYFa-like immunoreactivity in H. glaberrima, where immunoreactive fibers form
      a prominent and extensive peptidergic nervous system component. Neuron-like cells
      and nerve fibers expressing GFSKLYFa-like immunoreactivity are found in the
      ectoneural and hyponeural divisions of the radial nerve cords as well as in the
      digestive, haemal, respiratory, and reproductive systems; in the tentacles; and
      in tube feet. Neuroendocrine-like cells are found in the mucosal layer of the
      intestine. Ultrastructure immunocytochemical analysis revealed that, in nerve
      cells and fibers in the serosal layer of the intestine, the immunoreactivity is
      concentrated in vesicles. The immunoreactive nerve fibers are found mainly within
      a dense nerve plexus overlying and in close contact with smooth muscle cells of
      the intestine. The exclusive expression of GFSKLYFa-like immunoreactivity in
      neuronal or neuroendocrine tissue together with the close apposition of some
      fibers to muscle cells suggests that GFSKLYFa acts as a neuromuscular transmitter
      or neuromodulator in H. glaberrima. The wide occurrence of GFSKLYFa-like
      immunoreactivity throughout the nervous system of the sea cucumber suggests that
      GFSKLYFa plays an important role in the control of multiple action systems,
      including digestion, respiration, circulation, reproduction, and locomotion.

PMID- 7722005
TI  - Histopathological features in the small intestine of pigs infected with F4ac+ non
      enterotoxigenic or enterotoxigenic strains of Escherichia coli.
AB  - Four porcine strains of Escherichia coli were examined for their effects on the
      small intestine of 4-week-old weaned pigs infected orogastrically. The strains
      used experimentally were: strain 1467 (adhesin negative, non-toxigenic); strains
      2407 and 1466 (adhesin positive, non-toxigenic), derived by genetical engineering
      from strain 1467 and containing a wild type plasmid and a recombinant plasmid,
      respectively, encoding the F4 antigen (adhesin); and strain M1823 (adhesin
      positive, toxigenic). In addition, 2-week-old pigs that died from natural
      colibacillosis associated with two strains ("Ihan 1 and 2"; adhesin positive,
      toxigenic) were examined. Strain M1823 and the Ihan strains produced moderate and
      marked lesions, respectively. Strain 1467 did not cause mucosal damage or an
      inflammatory response. Strains 1466 and 2407 caused a mild to moderate leucocyte
      (mononuclear and polymorphonuclear) infiltration in the jejunal (but not ileal)
      lamina propria. However, unlike strain 1466, strain 2407 did not cause damage to
      the small intestinal mucosa and should be further studied as a potential oral
      vaccine strain for post-weaning E. coli diarrhoea.

PMID- 7722006
TI  - Pathophysiological response of bovine pulmonary function to gastric distension.
AB  - The purpose was to determine whether gastric overdistension leads to life
      threatening perturbations of pulmonary gas exchange in healthy calves. Six
      animals were studied with normal (0 kPa) and increased (1, 2, 3, 4 and 5 kPa)
      intragastric pressure (IGP). Changes in pleural pressures and peak expiratory
      flow paralleled those of IGP. Inspiratory pressure-time index remained stable
      throughout the insufflation process. Pulmonary function values were characterized
      by abrupt changes with increasing IGP. Tidal volume declined as IGP increased
      and, along with inspiratory flow, decreased abruptly with the highest pressure (5
      kPa). Respiratory rate progressively increased up to an IGP of 4 kPa, then
      decreased by 30%, due to breath-holding at the end of inspiration. Minute volume
      increased with IGP up to 4 kPa, but dramatically declined at 5 kPa. Total
      pulmonary resistance remained stable throughout the insufflation process, whereas
      lung dynamic compliance fell abruptly to one-half of its baseline value at IGPs
      of 1 kPa and above. Arterial oxygen tension was maintained at an IGP of 1 kPa,
      slightly diminished at 2-3 kPa, and markedly decreased at 4-5 kPa. Hypercapnia
      and respiratory acidosis developed progressively with increasing IGP. Changes in
      arterial gases were probably due to a combination of (1) alveolar
      hypoventilation, caused by altered tidal to dead space volume ratio, inadequate
      central nervous system "drive", altered effectiveness of inspiratory muscle
      action, or end-inspiratory breath-holding, and (2) ventilation to perfusion
      mismatch, caused by perfusion of collapsed lung units. In the range of IGPs used,
      standardized arterial pH did not decline below the control value, which suggests
      that perfusion of peripheral tissues remained sufficient, and that respiratory
      failure rather than cardiovascular failure may be the principal
      physiopathological effect of increased gastric pressure.

PMID- 7722007
TI  - Immunohistochemical studies of lymphoid tissues of rabbits infected with
      rinderpest virus.
AB  - The pathogenesis of infection with the L-strain of rinderpest virus (RPV) in
      rabbits was investigated. Of several lymphoid tissues examined, those associated
      with the gut showed the most marked virus growth. The virus titres were maximal 4
      days after inoculation but had declined at day 6. The distribution of viral
      antigen was examined immunohistochemically with the recently established anti
      rabbit CD5 monoclonal antibody (MoAb), which is a pan-T-cell marker, and the anti
      RPV-nucleoprotein MoAb. The virus antigen was localized in the CD5+ area at the
      initial stage of infection but spread to all areas of the lymphoid tissues at the
      later stages. By flow cytometric analysis with both rabbit CD5 and CD4 MoAbs, a
      decrease of the CD4+ and CD5+ subpopulations was observed in the spleen and
      mesenteric lymph nodes.

PMID- 7722008
TI  - Kinetics of the local and systemic antibody response to primary and secondary
      infection with S48 Toxoplasma gondii in sheep.
AB  - Vaccination of sheep with live tachyzoites of Toxoplasma gondii, strain S48,
      affords protection against subsequent challenge with the parasite, but the
      mechanisms of immunity have not been fully determined. To understand better the
      nature of the antibody response the kinetics of both local and systemic antibody
      production were monitored in vaccinated sheep by means of an enzyme-linked
      immunosorbent assay and Western blotting. Local specific IgG production was
      analysed in efferent lymph obtained from the cannulated pre-femoral lymph node
      draining the site of infection. Antibody in efferent lymph plasma and peripheral
      blood serum from animals vaccinated with S48 tachyzoites was monitored and
      compared with IgG production in vaccinated sheep given a secondary tachyzoite
      challenge. Secondary challenge resulted in a clear immunological memory response,
      antibody being detected in the lymph 3 to 4 days after infection as compared with
      7 to 8 days after a primary infection. IgG production was dominated by antibody
      recognizing a protein with an apparent molecular weight of 30 kDa, but other
      antigens (32, 24 and 11 kDa) were also readily detected.

PMID- 7722009
TI  - Ultrastructural, histochemical and immunohistochemical features of porcine
      intestinal lamina propria macrophages, peripheral blood monocytes and splenic
      adherent cells.
AB  - Ultrastructural, histochemical and immunohistochemical features of porcine
      intestinal lamina propria macrophages (LPMs), peripheral blood fibronectin
      adherent cells (FACs) and splenic-adherent cells (SPACs) were compared. Freshly
      isolated FACs and SPACs were small and showed small cytoplasmic processes, little
      evidence of endocytic vacuoles, few lysosomes and sparse rough endoplasmic
      reticulum (RER). Fresh FACs were negative for acid phosphatase, non-specific
      esterase (NSE) and beta-galactosidase activity. Of the SPACs, 20-40% were
      positive for acid phosphatase, < 5% for NSE and 5-10% for beta-galactosidase. Pre
      cultured FACs and SPACs were large and showed an abundance of endocytic vacuoles;
      they possessed dilated and prominent RER and > 95% were positive for the three
      enzyme activities. LPMs exhibited abundant endocytic vacuoles or vesicles and
      lysosomes but sparse RER, and > 85% were positive for the three enzymes. LPMs
      (24%), FACs (49%) and SPACs (40%) expressed MHC (major histocompatibility
      complex) class II glycoproteins. Macrophage-granulocyte antigens were detected in
      LPMs (14%), FACs (50%) and SPACs (33%). The results thus suggest that freshly
      isolated FACs differ from LPMs morphologically and in enzymic features, and the
      differences may represent part of the cell maturation process.

PMID- 7722010
TI  - Immunophenotypic characterization of cutaneous lymphoid neoplasia in the dog and
      cat.
AB  - Clinical, histopathological and immunohistochemical findings are presented from a
      series of cutaneous lymphoid neoplasms including canine epitheliotrophic lymphoma
      (n = 7), canine non-epitheliotrophic cutaneous lymphoma (n = 10), canine
      cutaneous plasmacytoma (n = 10) and feline non-epitheliotrophic cutaneous
      lymphoma (n = 6). Three cases of canine epitheliotrophic lymphoma expressed the
      CD3 T-lymphocyte marker, but the remainder were negative for this molecule and
      for a panel of B-cell markers. Non-epitheliotrophic cutaneous lymphoma was shown
      to be predominantly of T-cell phenotype (CD3+) in the dog (eight of 10 cases) and
      cat (five of six cases), the remaining cases in both species being of B-cell
      origin, expressing the gamma heavy chain of immunoglobulin (with or without
      lambda light chain). One canine non-epitheliotrophic B-cell lymphoma expressed
      IgG of the IgG2 subclass. Two of the biopsies from dogs with cutaneous
      plasmacotyoma were shown to express immunoglobulin alpha chain (one with lambda
      chain) and two neoplasms were positive for immunoglobulin gamma chain (both with
      lambda chain). One of the latter immunoglobulins was of the IgG4 subclass. In the
      majority of all cases of cutaneous lymphoid neoplasia examined, there was a local
      polyclonal immune response, manifested as infiltration by a mixed population of
      plasma cells expressing IgG (IgG2, IgG4), IgA or IgM. In the feline tumours CD3+
      small T lymphocytes were included in these infiltrates.

PMID- 7722011
TI  - Extrapulmonary silicosis in two water buffaloes.
AB  - Two cases of extrathoracic silicosis in buffaloes raised near a quartz quarry and
      suffering from clinically severe silicosis are described. The extrapulmonary
      changes were characterized by silicoconiotic nodules in the tonsils, mesenteric
      lymph nodes and spleen. A combination of energy dispersive X-ray microanalysis
      and scanning electron microscopy revealed that the mineral component of these
      lesions consisted mainly of silicon, aluminium, iron, calcium, magnesium, zinc,
      sulphur and potassium. It is concluded that domestic animals raised in polluted
      environmental conditions represent an important biological source from which
      helpful data may be obtained for assessing risks to human health and gaining new
      insight into pathogenetic mechanisms.

PMID- 7722012
TI  - Current therapy for cutaneous melanoma.
AB  - We review the current therapy for melanoma. The diagnosis, prognostic variables,
      staging, treatment, and follow-up guidelines for cutaneous melanoma are reviewed
      from the earliest to the most advanced stages. New guidelines for margins are
      discussed. A new, evolving, innovative radiographic technique, positron emission
      tomography using 2-fluorine-18-fluoro-2-deoxy-D-glucose, may be useful to
      identify subclinical nodal and visceral disease. Recent advances with respect to
      tumor vaccines, gene therapy, immunotherapy, and interleukin 2 as well as current
      concepts regarding lymph node dissection are discussed.

PMID- 7722013
TI  - Diagnostic immunohistochemistry of cutaneous metastatic breast carcinoma: a
      statistical analysis of the utility of gross cystic disease fluid protein-15 and
      estrogen receptor protein.
AB  - BACKGROUND: For accurate classification of cutaneous metastatic carcinoma,
      reliable tumor-specific immunohistochemical markers would be valuable. OBJECTIVE:
      Our purpose was to analyze the sensitivity, specificity, and positive predictive
      value of gross cystic disease fluid protein-15 (GCDFP-15) and estrogen receptor
      protein (ERP) for diagnosing cutaneous metastatic breast carcinoma. METHODS:
      Tissue sections from 68 consecutive cases of cutaneous metastatic carcinoma were
      stained for GCDFP-15 and ERP. Hematoxylin-eosin-stained slides and immunostained
      slides were reviewed in a blinded fashion before retrospective chart review to
      ascertain the underlying primary tumor type. RESULTS: Of 42 cases of cutaneous
      metastatic breast carcinoma, 30 were positive for GCDFP-15. Of 41 cases of
      metastatic breast carcinoma, 30 were positive for ERP. Calculated sensitivity,
      specificity, and positive predictive value for GCDFP-15 for diagnosing cutaneous
      metastatic breast carcinoma were 71%, 91%, and 94%, respectively, and 73%, 100%,
      and 100% for ERP, respectively. Combined values of these indices for both stains
      were 83%, 91%, and 95%, respectively. CONCLUSION: GCDFP-15 and ERP are valuable
      markers for cutaneous metastatic breast carcinoma and should be used in
      combination.

PMID- 7722014
TI  - Desmoplastic malignant melanoma.
AB  - BACKGROUND: Desmoplastic malignant melanoma (DMM) is an uncommon variant of
      malignant melanoma and often is difficult to diagnose. Because of the relative
      rarity of this tumor, it has not been well studied and controversy remains
      concerning its biologic potential. OBJECTIVE: We compared survival rates of DMM
      with those of other malignant melanomas and determined what clinical and/or
      histologic features, if any, correlated with survival. METHODS: The files of the
      Armed Forces Institute of Pathology were searched for cases of DMM or related
      tumors with adequate material for further histologic and immunohistochemical
      evaluation. Follow-up on each patient was requested from the pathologist,
      clinician, and/or the patient. The follow-up was correlated with the histologic
      findings in each case. The relationship of histologic features to disease-free
      survival was evaluated. RESULTS: Adequate material for evaluation was available
      in 128 cases. The overall histologic features were similar to those previously
      reported. Immunohistochemical studies showed that all lesions were negative for
      HMB-45, a marker for premelanosomes. Factors that correlated with survival
      included tumor location, sex, tumor depth, and the presence of stromal mucin. The
      5-year disease-free survival rate was 68% for all cases and 61% for lesions more
      than 4 mm deep. CONCLUSION: With a 5-year disease-free survival rate of 61%, DMM
      has a significantly better prognosis than other melanomas that have a 5-year
      disease-free survival rates of 40% to 41%. This may be related to neural
      differentiation of these tumors.

PMID- 7722015
TI  - A comparison of diagnosis, evaluation, and treatment of patients with
      dermatologic disorders.
AB  - BACKGROUND: Managed care in the American health care system may limit access to
      health care specialists. OBJECTIVE: We assessed primary care providers' abilities
      at diagnosing and treating patients with a previously undiagnosed skin disorder.
      METHODS: Patients with previously undiagnosed skin disorders were seen and
      examined sequentially by three groups of physicians: (1) internal medicine
      residents, (2) board-certified internal medicine attending physicians and (3)
      dermatology faculty. The internal medicine residents and attending physicians'
      diagnoses were compared with the dermatologists'. Appropriateness of therapy
      ordered by the internal medicine residents and attending physicians was assessed.
      RESULTS: Medical residents' diagnoses were correct in 43% of the patients whereas
      the attending physicians diagnosed 52% of cases correctly. Attending physicians
      and residents frequently ordered therapy inappropriate for the patient's
      diagnosis. Internal medicine residents and attending physicians were more likely
      to order skin biopsies than dermatologists. CONCLUSIONS: Our results confirm
      earlier studies that nondermatologists perform poorly in the diagnosis and
      treatment of skin disease. Primary care providers should receive more training in
      dermatology, or dermatologists should be permitted to act as primary caregivers
      to patients with skin disease.

PMID- 7722016
TI  - Detection of herpes simplex and varicella-zoster infection from cutaneous lesions
      in different clinical stages with the polymerase chain reaction.
AB  - BACKGROUND: The polymerase chain reaction (PCR) can be used to diagnose a variety
      of infectious processes. OBJECTIVE: We sought to determine whether Tzanck smear
      debris, vesicle fluid swabs, crusts, or fixed tissue specimens are the best
      source for template herpes simplex virus (HSV) or varicella-zoster virus (VZV)
      DNA for the PCR. METHODS: Patients with both clinical and histologic evidence of
      HSV (n = 6) or VZV (n = 16) infection were examined. Stained Tzanck smears,
      vesicle fluid swabs, dried crusts, and skin biopsy specimens were obtained at the
      same time from each patient. DNA was extracted from the different clinical
      specimens and then examined for HSV or VZV DNA with PCR. Fifteen control subjects
      did not have clinical or histologic evidence of herpesvirus infection. RESULTS:
      In cases of suspected VZV infection, PCR detected VZV DNA sequences from all 15
      Tzanck smears, all 15 vesicle swabs, one of one crust, and 14 of 16 fixed tissue
      specimens. HSV DNA sequences were detected from all six Tzanck smears, all four
      vesicle fluid swabs, two of two crusts, and five of six fixed tissue specimens.
      CONCLUSION: PCR can detect VZV and HSV DNA sequences from a variety of sources
      including formalin-fixed tissue specimens. Although viral DNA was detected
      slightly more frequently from Tzanck smear debris, crusts, and vesicle fluid
      swabs compared with fixed tissue specimens, each was an excellent source of
      target DNA for the PCR to confirm the diagnosis of herpesvirus infection.

PMID- 7722017
TI  - Malignant melanoma in Italy: risks associated with common and clinically atypical
      melanocytic nevi.
AB  - BACKGROUND: Most epidemiologic studies on risk factors for cutaneous melanoma
      have been performed in predominantly fair-skinned populations. OBJECTIVE: Our
      purpose was to assess by means of a case-control study the importance of common
      melanocytic nevi (CMN) and clinically atypical nevi (CAN) as risk factors for
      cutaneous melanoma in a Mediterranean population. METHODS: One hundred six
      patients with invasive cutaneous melanoma and 109 population control subjects
      were included in the study. All subjects were younger than 70 years of age and
      were residents of the Florence area. RESULTS: The adjusted odds ratios obtained
      by exact conditional analysis, accounting for age, sex, place of birth, and
      residence, were 2.6 (95 confidence interval [CI], 1.0 to 6.7) for 10 to 30 CMN,
      and 22.3 (CI, 4.8 to 215) for more than 30 CMN (chi 2 for trend, 25.41; p <
      0.001), 2.9 (CI, 1.2 to 7.5) for large nevi, and 8.4 (CI, 2.2 to 31.4) for CAN.
      Tendency to freckle resulted in a twofold increase in risk (odds ratio, 2.2) (CI,
      1.0 to 5.2). The relative risk associated with a large number of CMN was
      statistically significant after adjustment for all other variables. When adjusted
      for the number of CMN, none of the other variables showed a statistically
      significant increased risk. CONCLUSION: A large number of CMN represents the most
      important risk factor for cutaneous melanoma in the Italian population. The
      presence of large nevi and CAN did not result in an increased risk when the
      number of CMN was considered.

PMID- 7722018
TI  - Pleomorphic basal cell carcinoma.
AB  - BACKGROUND: A variant of basal cell carcinoma (BCC) with scattered large,
      pleomorphic cells has previously been reported as "basal cell epithelioma with
      giant tumor cells" and "basal cell carcinoma with monster cells." OBJECTIVE: Our
      purpose was to describe the clinical, histologic, and DNA ploidy findings in BCCs
      with these cytologic features. METHODS: Nineteen pleomorphic BCCs from 15
      patients were prospectively collected, and other BCCs in these patients were
      retrospectively reviewed by light microscopy. One lesion was recurrent. Seven of
      the pleomorphic BCCs and one nonpleomorphic BCC were studied by image analysis.
      RESULTS: These pleomorphic BCCs ranged from 2.8 to 12.5 mm in greatest diameter
      and were most commonly located on the head and neck. Five BCCs were present on
      the face and scalp of a patient with basal cell nevus syndrome. There have been
      no subsequent recurrences of the pleomorphic BCCs (follow-up from 3 to 32 months;
      median, 20 months). All 19 pleomorphic BCCs displayed characteristic features of
      BCC: peripheral palisading, stromal retraction, mucin production, and apoptosis.
      All 19 also showed huge pleomorphic mononucleated and multinucleated giant tumor
      cells. The nuclei of these large cells were often hyperchromatic with prominent
      nucleoli and abundant cytoplasm, and occasionally with intranuclear cytoplasmic
      protrusions. In addition, there were frequent and atypical mitoses in 47% of the
      cases. All pleomorphic BCCs studied by cell image analysis of formalin-fixed,
      paraffin-embedded tissue were aneuploid. The DNA content of the giant tumor cells
      was not a multiple of a single DNA value. CONCLUSION: Pleomorphic BCCs clinically
      present as typical BCCs. Despite their striking focal cellular atypia, these
      lesions seem to behave as ordinary BCCs.

PMID- 7722019
TI  - Raynaud's phenomenon together with antinuclear antibodies: a common subset of
      incomplete connective tissue disease.
AB  - BACKGROUND: The frequency of incomplete connective tissue disease (ICTD) is
      unknown. OBJECTIVE: Our purpose was to determine the frequency of Raynaud's
      phenomenon (RP) and antinuclear antibodies (ANA) in patients without definite
      connective tissue disease. METHODS: A series of 165 consecutive patients with RP
      was investigated. RESULTS: Fifty-one patients had primary RP; 60 had secondary
      RP; 54 patients were classified as having ICTD, 35 of whom had ANA and 19 of whom
      did not. Of the 35 patients who had ICTD with ANA, 29 were women and six were
      men. Their clinical findings were as follows: 17 had nonerosive arthritis, 14 had
      a nailfold capillary scleroderma pattern, 12 had puffy fingers, 10 had
      anticentromere antibodies, nine had sicca syndrome, seven had pernio, seven had
      esophagitis, six had fingertip ulceration, five had telangiectasia, four had
      malar eruption, four had myalgia, four had weight loss, four had exertional
      dyspnea, and three had photo-sensitivity. No patient exhibited life-threatening
      visceral complications or antitopoisomerase antibodies. CONCLUSION: In this
      series ICTD was more frequent than definite connective tissue disease. Many
      patients with RP have ICTD that is sometimes chronic.

PMID- 7722020
TI  - Double-blind, parallel-group comparison of terbinafine and griseofulvin in the
      treatment of toenail onychomycosis.
AB  - BACKGROUND: Griseofulvin has been used in the treatment of toenail onychomycosis
      with limited success. Evidence suggests that terbinafine may be more effective.
      OBJECTIVE: In a double-blind, parallel-group study we compared 250 mg/day
      terbinafine for 16 weeks with 500 mg/day griseofulvin for 52 weeks (or for
      shorter periods in cured patients) in patients with toenail onychomycosis.
      METHODS: Eighty-nine patients with culture-proved tinea unguium were included,
      and 43 in the terbinafine group and 41 in the griseofulvin group were assessable
      for efficacy. Patients who had not improved after 16 weeks were entered into an
      open study and were given 250 mg/day terbinafine for 16 weeks with the study code
      still blinded and were then followed up for 20 weeks. RESULTS: Terbinafine was
      significantly more effective than griseofulvin, with 42% being completely cured
      and 84% mycologically cured compared with only 2% with total cure and 45% with
      mycologic cure in the griseofulvin-treated group. The number of side effects was
      significantly lower in the terbinafine group (11%) compared with the griseofulvin
      group (29%). CONCLUSION: Terbinafine is significantly more effective than
      griseofulvin in the treatment of toenail onychomycosis.

PMID- 7722021
TI  - Treatment of dermatomyositis with methotrexate.
AB  - BACKGROUND: No published data exist on the incidence of liver fibrosis in
      patients with dermatomyositis treated with methotrexate. OBJECTIVE: Our purpose
      was to examine the efficacy, steroid-sparing potential, and side effects of
      methotrexate in patients with dermatomyositis and to report liver biopsy results
      in four patients. METHODS: A retrospective review of all cases of dermatomyositis
      treated with methotrexate in a dermatology and rheumatology referral practice was
      conducted. RESULTS: Of the 10 cases reviewed, seven were of dermatomyositis
      whereas three were of amyopathic dermatomyositis (ADM). Nine patients received
      oral methotrexate. One patient received intravenous methotrexate. Improvement of
      cutaneous disease occurred in seven (100%) of the patients with dermatomyositis
      and in two (66%) of those with ADM; myositis improved in four (57%) of the
      patients with dermatomyositis. The initial prednisone dose was halved after an
      average of 18 weeks of methotrexate therapy in the patients with dermatomyositis
      and 13 weeks in the patients with ADM. Methotrexate-related side effects occurred
      in six (86%) of the patients with dermatomyositis and in one (33%) of the
      patients with ADM. Of the four patients who had liver biopsies, two (50%) showed
      mild hepatic fibrosis, resulting in discontinuation of the drug. Both patients in
      whom fibrosis developed had preexisting steroid-induced diabetes mellitus.
      CONCLUSION: Although methotrexate is an effective treatment for dermatomyositis,
      side effects are common. Patients with diabetes mellitus should be closely
      monitored for toxic effects on the liver.

PMID- 7722022
TI  - Cutaneous manifestations of Prototheca infections.
AB  - The genus Prototheca comprises several species, the most prevalent of which is
      Prototheca wickerhamii. These achlorophyllic algae are found in the slime flux of
      trees and in freshwater environs. Cutaneous infection with these microbes was
      first reported 30 years ago. Subsequent case reports have described other
      manifestations including systemic disease. Asymptomatic and stationary cutaneous
      plaques may be seen in otherwise healthy patients. Susceptibility to infection is
      ill defined but may involve an inability of neutrophils to effectively eradicate
      phagocytosed organisms. Characteristic morula are seen histologically. Antifungal
      medications are the most effective therapy.

PMID- 7722023
TI  - Sulfur mustard: its continuing threat as a chemical warfare agent, the cutaneous
      lesions induced, progress in understanding its mechanism of action, its long-term
      health effects, and new developments for protection and therapy.
AB  - Although sulfur mustard (SM) has been used as a chemical warfare agent since the
      early twentieth century, it has reemerged in the past decade as a major threat
      around the world. SM is an agent that is easily produced even in underdeveloped
      countries and for which there is no effective therapy. This agent is a potential
      threat not only on the battlefield but also to civilian populations. The skin and
      other epithelial surfaces are the first targets as this agent is absorbed, and
      reactions within the skin are the subject of active research into the mechanism
      of action of this alkylating agent. The depletion of glutathione, generation of
      reactive oxygen species, and the formation of stable DNA adducts remain theoretic
      and demonstrated by-products of SM exposure implicated in the disease produced.
      However, new findings related to the effects of SM on the basement membrane zone;
      interest in delayed healing of the lesions induced; the inflammatory mediators,
      enzymes, and cytokines that result; and cellular typing of the inflammatory
      infiltrate will increase our understanding of the pathophysiology of the lesions
      caused by SM. In addition, the recent development of a topical skin protectant
      for SM and for other chemical warfare agents may have broad applications within
      dermatology.

PMID- 7722024
TI  - Surgical pearl: maintaining the alar groove.

PMID- 7722025
TI  - State and territorial regulation of tattooing in the United States.

PMID- 7722026
TI  - Who needs zebras? Comments on desmoplastic melanoma.

PMID- 7722027
TI  - Osteogenic sarcoma with skin metastases.

PMID- 7722028
TI  - Cutaneous extramedullary hematopoiesis.

PMID- 7722029
TI  - Intrafollicular mucin deposits in Pityrosporum folliculitis.

PMID- 7722030
TI  - Evolution of endemic pemphigus foliaceus (fogo selvagem) after HIV-1 infection.

PMID- 7722031
TI  - Tefillin dermatitis (a phylacteric phenomenon)

PMID- 7722032
TI  - Contact dermatitis from topical auranofin.

PMID- 7722033
TI  - Lymphoepithelioma-like carcinoma of the skin treated by Mohs micrographic
      surgery.

PMID- 7722034
TI  - Alopecia areata in a patient with pili annulati.

PMID- 7722035
TI  - Cutaneous metastases from carcinoma of the cervix resemble acquired lymphangioma.

PMID- 7722036
TI  - Exacerbation and induction of psoriasis by angiotensin-converting enzyme
      inhibitors.

PMID- 7722037
TI  - Posttransplant skin cancer: a possible role for p53 gene mutation but not for
      oncogenic human papillomaviruses.

PMID- 7722038
TI  - Lymphoproliferative disease of granular lymphocytes.
AB  - We report a case of lymphoproliferative disease of granular lymphocytes that was
      associated with cutaneous manifestations. Marker studies of skin and blood in
      this patient revealed that the circulating and infiltrating cells were negative
      for CD3 and T-cell antigen receptor but were positive for CD16, CD56, and CD57,
      suggesting natural killer cell origin. The patient had a rapidly progressive
      course and died within 1 month of presentation.

PMID- 7722039
TI  - Follicular spicules of the nose: a peculiar cutaneous manifestation of multiple
      myeloma with cryoglobulinemia.
AB  - We describe a patient with multiple myeloma and cryoglobulinemia who had spicules
      with a horny appearance in the follicular openings of the face, particularly on
      the nose. Histopathologic study demonstrated that these spicules consisted of
      eosinophilic homogeneous deposits in the intercellular spaces between
      keratinocytes in the upper layers of the follicular infundibulum. Direct
      immunofluorescence, ultrastructural, and biochemical investigations revealed that
      these eosinophilic deposits were cryoprecipitates composed of IgG-kappa with
      electrophoretic characteristics identical to those of the paraprotein present in
      the serum of the patient. Hence we believe that these lesions are best referred
      to as pseudohyperkeratotic spicules of the nose, and that they are a
      characteristic cutaneous manifestation of patients with multiple myeloma and
      cryoglobulinemia.

PMID- 7722040
TI  - Essential syphilitic alopecia revisited.
AB  - There has been a resurgence of syphilis in the past decade. Uncommonly, diffuse
      hair loss, termed essential alopecia, is the only sign of syphilitic infection.
      We describe two patients with syphilis in whom the first sign of disease was
      alopecia and discuss the clinical and histopathologic findings of essential
      syphilitic alopecia.

PMID- 7722041
TI  - Cutaneous manifestations of disseminated cryptococcosis.
AB  - Disseminated cryptococcosis is a life-threatening infection with cutaneous
      dissemination in 10% to 20% of cases. We describe seven patients with
      disseminated cryptococcosis with variable cutaneous manifestations. AIDS was a
      predisposing factor in six patients. Cutaneous presentations included a draining
      sinus tract, verrucous nodules, molluscum-like lesions and erythematous,
      indurated plaques. Histologically, all lesions revealed numerous encapsulated
      cryptococcal organisms in a gelatinous pattern, highlighted with periodic acid
      Schiff, mucicarmine, and methenamine silver stains. The patients responded
      variably to treatment with amphotericin B, flucytosine, and fluconazole.

PMID- 7722042
TI  - Systemic mastocytosis associated with chronic myelomonocytic leukemia: clinical
      features and response to interferon alfa therapy.
AB  - Systemic mastocytosis is a rare disease that shows marked heterogeneity in
      clinical manifestations and prognosis. It may be associated with hematologic
      disorders. We describe a patient with systemic mastocytosis associated with
      chronic myelomonocytic leukemia accompanied by ascites, pleural effusion, and
      development of skin lesions along a surgical scar. The disease responded well to
      interferon alfa therapy. This is the second report of successful treatment of
      mastocytosis with interferon alfa and the first associated with a hematologic
      malignancy.

PMID- 7722043
TI  - Zosteriform metastases in melanoma.
AB  - Zosteriform metastasis is a rare form of tumor spread to the skin that most often
      arises from an internal carcinoma or a hematologic malignancy. We describe a 29
      year-old woman with malignant melanoma of the back in whom zosteriform metastases
      developed along the fifth thoracic dermatome.

PMID- 7722044
TI  - Neonatal lupus erythematosus: discordant disease expression of U1RNP-positive
      antibodies in fraternal twins--is this a subset of neonatal lupus erythematosus
      or a new distinct syndrome?
AB  - Neonatal lupus erythematosus (NLE) is an uncommon disease that is manifested by
      cutaneous lesions, cardiac conduction defects, or both, that appear in utero or
      shortly after birth. In approximately 95% of patients, anti-Ro antibody (Ro[SS
      A]) has been identified and has become the serologic marker for NLE. Since 1987
      there have been four reported cases of Ro- and anti-La antibody (La[SS-B])
      negative, U1RNP antibody-positive, NLE. Our affected twin, as well as all other
      infants with U1RNP-positive NLE, had cutaneous lesions similar to those in Ro
      positive NLE, although they lacked systemic abnormalities, including cardiac
      conduction defects. HLA typing of mothers with infants with U1RNP-positive NLE
      revealed the presence of HLA-DR4, DQw1, or DQw3 phenotypes. Our typing confirms
      these findings. As with Ro-positive NLE, no distinct HLA associations were
      demonstrated in the infants. Unlike Ro-positive mothers, all mothers with a U1RNP
      positive infant with NLE had connective tissue disease at the time of the
      diagnosis and had a different spectrum of disease. We describe the clinical,
      serologic, and immunogenetic findings in the first reported case of U1RNP
      positive NLE in dizygotic twins in whom the NLE disease expression was
      discordant.

PMID- 7722045
TI  - Erythromelanosis follicularis faciei in women.
AB  - Erythromelanosis follicularis faciei is an infrequently diagnosed disorder
      thought to be more common in men, with only seven reported cases in women. This
      condition consists of the clinical triad of well-demarcated erythema,
      hyperpigmentation, and follicular plugging on the face. We describe two
      additional female patients with this condition and present a review of the
      literature.

PMID- 7722046
TI  - Treatment of cutaneous and pulmonary sarcoidosis with thalidomide.
AB  - Many therapeutic agents have been proposed for treatment of steroid-resistant
      sarcoidosis. Because administration of low doses of thalidomide has been
      successful in treating other inflammatory diseases, it was used in a patient with
      systemic sarcoidosis who was unresponsive to corticosteroids and in a patient
      with pulmonary sarcoidosis, in whom Kaposi's sarcoma developed after a course of
      corticosteroid therapy. Thalidomide, 200 mg/day for 2 weeks followed by 100
      mg/day for 11 weeks, was given. This treatment was effective in both patients. No
      adverse reactions were observed. Thalidomide, 100 mg on alternate days, is still
      being administered. No relapse has occurred. Thalidomide, particularly because of
      its inhibition of the macrophage function, may be a useful alternative therapy in
      steroid-resistant cases. In addition, the correlation between the angiotensin
      converting enzyme level and the clinical improvement observed in our patients
      suggests a direct parallel between angiotensin-converting enzyme and the activity
      of the granulomatous process.

PMID- 7722047
TI  - Malignant proliferating trichilemmal cyst.
AB  - We report a case of a metastasizing proliferating trichilemmal cyst. A 78-year
      old man had multiple common and two proliferating trichilemmal cysts, one of
      which showed malignant transformation as evidenced by lymph node metastases.
      Despite surgical removal of the malignant tumor, extensive metastatic disease
      rapidly occurred. This case exemplifies the difficulties in diagnosis and
      treatment of these rare tumors and their unpredictable course.

PMID- 7722048
TI  - Congenital erosive and vesicular dermatosis with reticulated, supple scarring: a
      neutrophilic dermatosis.
AB  - Congenital erosive and vesicular dermatosis with reticulated, supple scarring is
      a rare disease seen at birth with blisters that become eroded and crusted and
      then heal with characteristic scars. We report the seventh case in the American
      literature, and the first description of biopsy specimens of early lesions. The
      acute skin lesions were characterized by sterile, neutrophilic infiltrates in the
      dermis.

PMID- 7722049
TI  - Atrial myxoma with livedoid macules as its sole cutaneous manifestation.
AB  - We report the second case of atrial myxoma associated with livedoid macules
      representing an embolic phenomenon. This case of atrial myxoma was of the
      sporadic type with no associated syndrome (such as the LAMB or NAME syndrome or
      Carney complex). A skin biopsy specimen from fading livedoid macules on the
      extremities showed a myxoid embolus inside dermal vessels, a diagnostic clue to
      the presence of an atrial myxoma. The histologic features of such lesions should
      alert the clinician to the presence of an otherwise silent atrial myxoma. Early
      surgical intervention may prevent the onset of severe neurologic deficits in such
      patients.

PMID- 7722050
TI  - Lichen planus pemphigoides: identification of 180 kd hemidesmosome antigen.
AB  - We describe a man with lichen planus pemphigoides. Direct immunofluorescence
      studies of peribullous skin showed linear deposition of IgG and C3 in the
      basement membrane zone. Indirect immunofluorescence studies disclosed circulating
      anti-basement membrane zone antibodies. Immunoelectron microscopy demonstrated
      binding of antibodies to the hemidesmosomes and lamina lucida. The patient's
      serum defined only the minor bullous pemphigoid antigen with a molecular weight
      of 180 kd. These findings suggest the coexistence of lichen planus and bullous
      pemphigoid in lichen planus pemphigoides.

PMID- 7722051
TI  - De novo development of psoriatic plaques in patients receiving interferon alfa
      for treatment of erythrodermic cutaneous T-cell lymphoma.
AB  - Presumably because of its potent immunomodulatory activity, the use of interferon
      has led to the development of autoimmune disease in susceptible individuals.
      Because psoriasis is considered to be, in part, an autoimmune phenomenon, it is
      plausible that interferon may influence disease activity. We describe the
      development of psoriatic plaques in two patients without a history of this
      disease while they were receiving interferon alfa and extracorporeal
      photochemotherapy for erythrodermic cutaneous T-cell lymphoma. Paradoxically, in
      both patients the erythroderma resolved with subsequent de novo onset of
      psoriasis. This clinical sequence provides support for disparate immune
      mechanisms in the pathogenesis of these disorders, both of which are typified by
      lymphoid infiltrates. A review of the literature reveals that all forms of
      interferons have been associated with the exacerbation of psoriatic plaques, but
      that only interferon alfa has induced de novo development of psoriasis.

PMID- 7722052
TI  - Porokeratosis and Crohn's disease.
AB  - We report the cases of three patients with Crohn's disease in whom porokeratosis
      developed. Disseminated superficial actinic porokeratosis developed in two
      patients. In one of these patients, the skin lesions arose during an exacerbation
      of the bowel disease. In the third patient, who had congenital linear
      porokeratosis, the disseminated superficial form of the disorder developed during
      the first severe exacerbation of Crohn's disease. A family history of
      porokeratosis was present in one patient, but no relatives of any of these
      patients were known to have Crohn's disease. In all three patients, Crohn's
      disease was limited to the colon.

PMID- 7722053
TI  - Mycetoma caused by Acremonium falciforme: successful treatment with itraconazole.
AB  - Mycetoma has not been previously reported in Korea. A case of mycetoma caused by
      Acremonium falciforme in a 72-year-old man is described. The patient had a
      single, large, well-demarcated, erythematous, swollen, black, escharlike lesion
      and three small satellite lesions on his right temporal area. He was treated with
      itraconazole, and all lesions healed with residual scars in 70 days.

PMID- 7722054
TI  - Multiple dermatofibromas in a woman with HIV infection and systemic lupus
      erythematosus.
AB  - Associations of multiple dermatofibromas with autoimmune disorders, altered
      immunity, or both have been described. We report the case of a 33-year-old black
      woman with HIV infection and an 11-year history of systemic lupus erythematosus
      in whom 15 dermatofibromas developed while she was receiving systemic
      corticosteroid therapy. Including our patient, multiple dermatofibromas have been
      described in 15 patients with an autoimmune disease, altered immunity, or both.
      All 12 of the women with multiple dermatofibromas had systemic lupus
      erythematosus.

PMID- 7722056
TI  - Atypical varicella-zoster virus infection in an immunocompromised patient: result
      of a virus-induced vasculitis.
AB  - We describe a patient with cutaneous T-cell lymphoma in whom persistent,
      painless, ecthymatous nodules developed as a result of a varicella-zoster virus
      infection. The localized infection occurred without a vesicular stage.
      Ultrastructural studies revealed a lack of epidermal involvement and massive
      varicella-zoster virus replication within endothelial cells, leading to an
      obliterative vasculitis. This suggests direct infection of dermal vessels from
      adjacent nerves, bypassing the epidermis, which is usually infected first in the
      classic infectious pathway during varicella-zoster virus reactivation from
      sensory nerves.

PMID- 7722055
TI  - Costello syndrome.
AB  - Costello syndrome is an uncommon multisystemic condition with highly
      characteristic cutaneous manifestations. We describe here the case of a patient
      with Costello syndrome, and review previous reports of this entity.

PMID- 7722057
TI  - Pyoderma gangrenosum in an HIV-infected patient.
AB  - Pyoderma gangrenosum has previously been reported in four patients with HIV
      infection. We describe here the case of a fifth HIV-infected patient with
      pyoderma gangrenosum and review the characteristics of the four previously
      reported cases.

PMID- 7722058
TI  - Dental specialists and IADR.

PMID- 7722059
TI  - NIDR--a view from the inside.

PMID- 7722060
TI  - Effects of potassium ions on action potential conduction in A- and C-fibers of
      rat spinal nerves.
AB  - Potassium ions in dentifrices for treating 'hypersensitive' dentin are believed
      to act directly on intradental nerves by raising extracellular potassium ion
      concentration ([K+]o) sufficiently to prevent action potential generation by
      axonal accommodation. However, the [K+]o necessary to block nerve conduction is
      not precisely known, nor is it certain that K+ can diffuse from a dentifrice in
      sufficient amounts to inactivate intradental nerves. To establish more accurately
      the [K+]o required to block nerve conduction under controlled conditions, we
      studied the effects of increased [K+]o on the sizes of compound action potentials
      (CAP) recorded from rat spinal nerves in vitro. [K+]o was increased by the
      addition of either KCl or KNO3 to Krebs' solutions applied to the central portion
      of the nerves. CAP attenuation increased in a dose-dependent manner as [K+]o was
      raised in the 8 to 64 mmol/L range, and complete block was generally produced
      with solutions containing at least 32 mmol/L K+. CAP attenuation was reversible,
      and recovery times increased with increasing [K+]o. The effects of KCl and KNO3
      solutions were the same for all [K+]o tested. Half-maximal (50%) reduction in the
      A beta-fiber component of the CAP occurred with 17.4 mmol/L K+, and with 17.8
      mmol/L and 19.3 mmol/L K+, respectively, for the A delta- and C-fiber components.
      Control experiments with glucose and choline chloride confirmed that the
      conduction block observed with increased [K+]o was not due to increased solution
      osmolarity or ionic strength.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722061
TI  - Weakness in mouse masticatory muscles by repetitive contractions with forced
      lengthening.
AB  - The etiology of myofascial tenderness and pain of masticatory muscles in humans
      is difficult to understand. Parafunctional oral habits such as tooth grinding or
      vigorous chewing are thought to be factors. The objective of this study was to
      determine if masticatory muscles are susceptible to weakness and injury induced
      by repetitive, dynamic, forced-lengthening contractions. Results would support
      the hypothesis that contraction-induced injuries could occur in hyperactive
      masticatory muscles of humans in response to parafunctional oral habits. Mice
      were anesthetized and randomly assigned to three groups: non-treated controls,
      treated by repetitive passive jaw opening, or treated by repetitive isometric
      tetanic contractions with lengthening by jaw opening. In each treatment group,
      masticatory muscle injury was evaluated by contractile tension, plasma creatine
      kinase, and muscle glycogen. Contractile tension was determined at different
      stimulation frequencies and was significantly decreased 5 min, 4 h, and 72 h
      after repetitive contraction/lengthening. Plasma creatine kinase was
      significantly elevated at 4 but not at 72 h post-treatment in mice subjected to
      repetitive contraction/lengthening. Masticatory muscle glycogen was not
      significantly different in any groups at 4 or 72 h post-treatment. These results
      indicate that contraction injuries can be induced in masticatory muscle of mice
      by forced lengthening contractions which simulate eccentric contractions.

PMID- 7722062
TI  - Specific and charge interactions mediate collagen recognition by oral
      lactobacilli.
AB  - The mechanisms by which oral lactobacilli, one of the three major genera of
      cariogenic bacteria, attach to tooth surfaces are unknown. We hypothesize that
      recognition of collagen, the major component of dentin, may be a mechanism which
      localizes these bacteria to exposed root surfaces as well as to carious lesions
      which have penetrated the dentin. We found that the majority of oral
      Lactobacillus spp. strains recognize and bind collagen type I. Binding of 125I
      labeled collagen type I to two strains of L. casei rhamnosus has been
      characterized in some detail. These strains were previously characterized with
      respect to their attachment to dentin (Switalski and Butcher, 1994). The process
      of 125I-collagen binding was mediated via specific as well as charge
      interactions. The putative adhesin-mediated (specific) interaction involved a
      limited number of bacterial surface components (2 x 10(3)/cell). Under conditions
      conducive for non-specific interactions (low ionic strength), the binding was
      higher by an order of magnitude. Collagen binding strains were found to adhere to
      collagen-coated surfaces, while strains unable to bind collagen adhered to a much
      lesser extent. Adherence of bacteria to collagen-coated surfaces could be
      competitively inhibited with collagen. These interactions may target collagen
      binding strains of lactobacilli to dentin collagen in the oral cavity and thus
      play a role in the pathogenesis of root surface and/or coronal caries.
      Interference with this collagen-mediated attachment of lactobacilli may provide
      effective means of caries control, particularly in view of the fact that other
      oral acidogenic microbiota also interact with collagen.

PMID- 7722063
TI  - Antigen specificity of serum antibody in A. actinomycetemcomitans-infected
      periodontitis patients.
AB  - We hypothesized that serum antibody with selected antigen specificities would
      relate to infection and disease in the patients and, thus, describe the
      characteristics of potential protective antibody. This study used serum samples
      from 24 periodontitis patients with subgingival infection and elevated serum IgG
      antibody to A. actinomycetemcomitans to define the antigenic specificities of
      IgG, IgM, IgA, and IgG1-4 antibody to A. actinomycetemcomitans strain Y4 outer
      membrane antigens (OMA). Uniform IgG antibody (> 70% of the patients) was noted
      to antigens with M(r) of 65, 38, 29, and 17 kDa. Both IgA and IgM specificities
      reflected those shown for IgG in each patient. IgG1 and IgG2 antibody reacted
      with several OMA bands in each patient, while IgG3 antibodies were directed to
      numerous OMA bands in many patients and represented the most broad-based
      response. The IgG4 response patterns were limited to a few OMA bands. We noted a
      prominent occurrence of IgG reactions with OMA bands that were characteristic for
      individual patients. The frequency of responses to OMA of higher M(r) (i.e., > 80
      kDa) and to the 34-, 31-, and 24-kDa antigens was positively related to the total
      IgG antibody levels. Antibody reactive with OMA bands at 65-, 38-, 29-, 17-, 15-,
      and 11-kDa antigens was detected in patients with few to many teeth infected with
      A. actinomycetemcomitans. Furthermore, patients with a high percentage of teeth
      with > or = 6 mm pockets had a decreased frequency of responses to the high-M(r)
      antigens (i.e. > 90 kDa) as well as to the 58-kDa antigen.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7722064
TI  - Three-year tooth loss among black and white older adults in North Carolina.
AB  - The distribution and determinants of tooth loss in older adults are poorly
      defined, especially in Blacks, who have been underrepresented in previous
      studies. This study investigated, epidemiologically, the distribution and
      predictors of tooth loss in elder Blacks and Whites by following a random sample
      of older adults in North Carolina for three years. It was hypothesized that
      Blacks would be at greater risk of tooth loss and would have different risk
      factors for tooth loss. Data from 263 Blacks and 228 Whites were collected by
      dental examinations and interviews conducted in the participants' homes. During
      the three-year follow-up, 53% of Blacks and 29% of Whites lost at least one
      tooth. Blacks lost 13% of their remaining teeth compared with 4% for Whites.
      Logistic regression models showed that factors related to tooth loss for Blacks
      were: more S. mutans in stimulated saliva, deeper periodontal pockets, more P.
      intermedia in subgingival plaque, high blood pressure, limited help from others,
      and few symptoms of depression. For Whites, significant factors were: more
      lactobacilli in stimulated saliva, history of current oral pain at baseline, more
      alcohol consumption, no history of past use of calcium or xerostomic medications,
      higher income, lower occupational prestige, and increased numbers of negative
      life events. This study showed that older Blacks were at greater risk of tooth
      loss than older Whites. For both races, factors such as oral bacteria,
      periodontal conditions, oral symptoms, and psychosocial and economic factors are
      related to increased risk of tooth loss.

PMID- 7722065
TI  - The fidelity of initial acquisition of mutans streptococci by infants from their
      mothers.
AB  - Previous cross-sectional studies using bacteriocin profiles, serotyping, or
      genotyping suggest that mothers are the principle source of mutans streptococci
      (MS) to their infants. This study determined the commonality of MS genotypes
      between mothers and their infants at the time of initial acquisition. Oral
      bacteria of mothers and their infants were monitored from birth for approximately
      3 years at three-month intervals. Genotypes of MS in infants appeared identical
      to those present in mothers in approximately 71% of 34 mother-infant pairs
      studied. Interestingly, female infants acquired MS genotypes identical to their
      mothers' with significantly greater fidelity than male infants (88% vs. 53%).
      Homology of genotypes between mothers and their infants at initial acquisition
      strongly suggests that MS strains were transmitted from mother to infant and that
      this transfer exhibited gender specificity. In no instance did we observe
      homology of genotypes between fathers and infants or fathers and mothers, further
      supporting the notion that acquisition of MS in humans follows maternal lines.
      Although the prevalence of dental caries was low in this young child population
      (11/34; 32%), we observed that male children who harbored the same genotype as
      their mothers had a 13 times greater likelihood of having caries than female
      children who acquired their mothers' strain; this difference was statistically
      significant (p < 0.01). Although we do not know the biological mechanisms
      governing fidelity of acquisition between a mother and her infant, our data
      suggest that caries outcome may be, in part, determined by both the source of MS
      and the presence of a specific genotype of MS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722066
TI  - Association of free arginine and lysine concentrations in human parotid saliva
      with caries experience.
AB  - We determined the free-amino acid content of stimulated parotid (ductal) saliva
      from two groups of adult subjects whose caries experiences were markedly
      different. The levels of free arginine and free lysine in the parotid saliva of
      caries-free adults were significantly higher than those found in the parotid
      saliva of individuals with a history of dental decay. There was no correlation,
      however, between the levels of these amino acids and the DMFS score within the
      caries-susceptible groups. Microbial catabolism of dibasic amino acids
      contributes to the neutralization of plaque acids and may partially account for
      the higher resting plaque pH observed in caries-free subjects. Alternatively, the
      elevations observed in free levels of arginine and lysine may reflect a systemic
      alteration in amino acid metabolism which is common to the caries-free group of
      subjects.

PMID- 7722067
TI  - The diffusion and enzymic hydrolysis of monofluorophosphate in dental plaque.
AB  - Although the ability of dental plaque to hydrolyze sodium monofluorophosphate
      (MFP) has been known for some time, its effect on the F- concentration at the
      plaque-enamel interface is undefined. We have determined enzyme kinetic values
      for MFP hydrolysis and diffusion coefficients so that the penetration and
      degradation of MFP in plaque can be modeled by computer. The KM and Vmax values
      for natural human plaque were 1.77 mmol/L and 41.4 nmol/min/mg protein,
      respectively, at pH 8.0. At pH 6.0, the Vmax was lower, 15.6 nmol/min/mg, but KM
      was not significantly different. Competitive inhibition by orthophosphate gave a
      Ki of 4.55 mmol/L. The diffusion coefficient for MFP in artificial plaque was
      1.91 x 10(-6) cm2/sec. When these data were used for mathematical modeling of the
      effects of rinsing with MFP and F- solutions, compared with an equivalent NaF
      application, the concentration of F- from MFP was lower at the inner surface of
      plaque, and the peak occurred later. Both pH and plaque thickness had a marked
      effect on the amount of MFP that could penetrate: At pH 8.0, almost none reached
      the inner surface of a 1-mm-thick plaque intact. At pH 6.0, however, more MFP was
      able to penetrate, due to lower MFPase activity. While MFP diffusion is
      inherently slower than that of F-, enzymic degradation increases the gradient for
      inward diffusion. If the conventional view that MFP in toothpaste acts as a
      source of F- is true, then MFP toothpaste should be formulated to optimize MFPase
      activity in dental plaque.

PMID- 7722068
TI  - Problems associated with estimation of net calcium uptake during enamel formation
      using 45Ca.
AB  - 45Ca uptake in mineralizing tissues may occur by net Ca uptake or by isotopic
      exchange. It is rarely possible to differentiate between these effects, making
      interpretation of the findings difficult. Unfortunately, this problem is not
      often considered, and 45Ca uptake is usually regarded as representative of only
      net calcium uptake. The study reported here was undertaken to estimate the extent
      to which 45Ca uptake in mineralizing enamel is due to net Ca deposition or to
      isotopic exchange, and to consider the implications. The enamel surfaces of the
      lower incisors of adult rats were notched at the gingival line, and the eruption
      distance over 16 hours was measured. This distance was used to establish the
      position of a 0.3-mm-wide increment of enamel at the beginning and end of the 16
      hour period, during which it passed through the early-maturation stage of enamel
      formation. The rate of Ca uptake was determined by chemical assay. Other rats
      were injected with 45Ca, mean plasma specific activity values for the
      experimental period determined, and the rate of Ca uptake through the same area
      of enamel formation was estimated. The estimates were from two- to nearly ten
      fold greater than those established by chemical assay, indicating that from 50 to
      90% of the 45Ca uptake occurred by isotopic exchange. 45Ca uptake may indicate
      more about the labile state of Ca in mineralizing enamel than about the rate of
      mineral deposition.

PMID- 7722070
TI  - Acute toxicity of carbamide peroxide and a commercially available tooth-bleaching
      agent in rats.
AB  - Previous studies have indicated that tooth-bleaching agents contain potentially
      hazardous chemicals. The present study evaluates the acute toxicity of a
      commercially available tooth-bleaching agent and carbamide peroxide, which is the
      active bleaching ingredient. Rats were dosed by stomach gavage, i.e., via a
      stomach tube, with 5, 15, and 50 mg carbamide peroxide/kg body weight and 150 and
      500 mg tooth-bleaching agent/kg body weight, corresponding to 15 and 50 mg
      carbamide peroxide/kg body weight. Animals were killed after either one or 24 h.
      Autopsies were performed, and the distal part of the esophagus and the stomach
      were removed and processed for light microscopy investigation. Liver and kidney
      were evaluated histologically in animals killed after 24 h. Carbamide peroxide
      gave dose-dependent ulcerations of the gastric mucosa, with the 15 mg/kg body
      weight as the lowest observed effect level. The lesions were clearly visible
      after one h and seemed to be healing after 24 h. The ulcerations of the gastric
      mucosa were more pronounced after exposure to the tooth-bleaching agent than
      those observed after a comparable dose of carbamide peroxide. This may be
      attributed to the hydrophobic gel and the content of a carbopol (which increases
      the tissue adherence and retards the release of oxygen) in the bleaching agent.
      No apparent injury was observed in livers and kidneys. An exposure limit based on
      the lowest observed effect level (15 mg carbamide peroxide/kg body weight) and a
      safety factor of 100 were established and utilized in a risk assessment which
      indicated that daily human exposure during a bleaching procedure may come close
      to or even exceed this limit.

PMID- 7722069
TI  - Characterization of cellular responses involved in reparative dentinogenesis in
      rat molars.
AB  - During primary dentin formation, differentiating primary odontoblasts secrete an
      organic matrix, consisting principally of type I collagen and non-collagenous
      proteins, that is capable of mineralizing at its distal front. In contrast to
      ameloblasts that form enamel and undergo programmed cell death, primary
      odontoblasts remain metabolically active in a functional tooth. When dentin is
      exposed to caries or by operative procedures, and when exposed dentinal tubules
      are treated with therapeutic dental materials, the original population of
      odontoblasts is often injured and destroyed. The characteristics of the
      replacement pool of cells that form reparative dentin and the biologic mechanisms
      that modulate the formation of this matrix are poorly understood. Based on the
      hypothesis that events governing primary dentinogenesis are reiterated during
      dentin repair, the present study was designed to test whether cells that form
      reparative dentin are odontoblast-like. Cervical cavities were prepared in rat
      first molars to generate reparative dentin, and animals were killed at various
      time intervals. In situ hybridization with gene-specific riboprobes for collagen
      types I and III was used to study de novo synthesis by cells at the injured
      dentin-pulp interface. Polyclonal antibodies raised against dentin sialoprotein
      (DSP), a dentin-specific protein that marks the odontoblast phenotype, were used
      in immunohistochemical experiments. Data from our temporal and spatial analyses
      indicated that cells forming reparative dentin synthesize type I but not type III
      collagen and are immunopositive for DSP. Our results suggest that cells that form
      reparative dentin are odontoblast-like.

PMID- 7722072
TI  - International Association for Dental Research divisional abstracts.

PMID- 7722071
TI  - Factors affecting the adherence energy of experimental resin cements bonded to a
      nickel-chromium alloy.
AB  - Reliable adherence of resin-based cements is of prime importance for the
      longevity of cemented restorations. The present study investigated whether a
      relationship exists between adherence energy to a metal substrate and the degree
      of cross-linking and wetting characteristics of resin-based luting agents. The
      adherence energies between a sand-blasted metal surface and a series of
      experimental resin cements were measured by means of the wedge test. The degree
      of cross-linking was calculated from the monomer composition of the resin
      cements. The measured wetting characteristics were work of adhesion and surface
      tension, and their dispersive and polar components. Adherence energy varied
      between 22 and 81 J/m2 and was influenced by the nature of the resin cements:
      Those with a low degree of cross-linking resulted in high adherence values.
      Furthermore, resin cements whose monomers were relatively polar gave rise to high
      adherence values. Although other metals may not behave in exactly the same way,
      these results may help in the formulation of new, more retentive resin cements.

PMID- 7722073
TI  - Soft edges--organizational structure in dental education.
AB  - There is no one best organizational structure for dental schools or for their
      major subunits. The classical alternatives of functional and divisional
      organization are discussed in light of the rule that follows function, and the
      advantages and disadvantages of each are presented. Newer models-
      decentralization, matrix, and heterarchy--show how features of functional and
      divisional structure can be blended. Virtual organizations, systems theory, and
      networks are also considered as new expressions of classical structures. The
      principle of suboptimization (soft edges) is presented.

PMID- 7722074
TI  - Designing preclinical instruction for psychomotor skills (III)--Instructional
      engineering: design phase.

PMID- 7722075
TI  - Comparison of dental school and practicing dentists' restorative treatment
      recommendations.

PMID- 7722076
TI  - Medical emergency education in dental hygiene programs.

PMID- 7722077
TI  - Science and dental education.

PMID- 7722078
TI  - Development of a computer program for teaching periodontal diagnosis based on
      clinical epidemiological principles.
AB  - Multimedia teaching tools in dental education are still rare. This paper
      describes the development of an inexpensive yet powerful computer program for
      instruction in the principles of clinical epidemiology. The application was
      developed in the context of periodontal diagnostic methodologies at the third
      year D.D.S. level. Principles of probabilistic thinking are invoked as the
      student is guided from the application of raw research data to the derivation of
      likelihood ratios and how they affect clinical decision making. A questionnaire
      was used to evaluate student satisfaction with the program and the responses
      indicated good acceptance of the concepts presented in the program and an
      interest in further computer-aided instruction.

PMID- 7722079
TI  - Using a Delphi Technique in a needs assessment for an innovative approach to
      advanced general dentistry education.
AB  - The University of Kentucky College of Dentistry has been awarded a $500,000 grant
      to develop and test a university-based educational program leading to a graduate
      certificate in Advanced General Dentistry, by the use of "extended campus" and
      distance learning methods. As an aid in developing this curriculum, dentists in
      general practice in non-urban Kentucky were asked about their educational needs.
      A Delphi Technique approach to this assessment was adopted. Forty dentists in
      general practice in non-urban areas in eastern and southern Kentucky were sent
      four mailings in which they rated or re-rated 65 topics for inclusion in the
      curriculum. A total of 59 topics were voted to be essential or desirable for the
      curriculum, 40 of them by a 2/3 majority. The Delphi Technique was workable for
      involving students in curriculum design. The curriculum produced by this method
      has also proven to be attractive to the dentists and their colleagues.

PMID- 7722080
TI  - Management of scales and other insect debris: occupational health hazard in a
      lepidopterous rearing facility.
AB  - Scales and other body parts of Lepidoptera are known allergens and pose a serious
      health hazard for workers in rearing programs. Researchers of the Crop Science
      Research Laboratory (USDA-ARS), located at Mississippi State, MS, have reared
      lepidopterous insects since the late 1960s. Efforts have been made by them to
      continuously improve management of the moth scale problem and reduce allergic
      reactions suffered by workers. We developed strategy that requires a separate
      facility for housing the moth colonies, oviposition cages that facilitate exit of
      scales and other debris, an improved air filtration system, and sanitation
      procedures. The strategy used currently (coined ALERT for Advanced Lepidoptera
      Environmental Rearing Technology) for scale management efficiently minimizes this
      serious occupational hazard.

PMID- 7722081
TI  - Direct effects of recombinant nuclear polyhedrosis viruses on selected nontarget
      organisms.
AB  - A limitation to effective field use of naturally occurring nuclear polyhedrosis
      viruses (NPVs) is the slow rate at which they kill their host. In making NPVs a
      more attractive pest management tool, this problem has been addressed by
      modifying NPVs genetically to express insecticidal proteins resulting in
      substantial increases in their speed of action. One concern associated with these
      recombinant NPVs, however, is their effects on nontarget insects associated with
      pests targeted for control by applications of NPVs. Our studies evaluated the
      direct effects of wild-type Autographa californica NPV (AcNPV) and a recombinant
      AcNPV (AcAaIT) on three insects beneficial to production agriculture. The
      recombinant NPV expresses an insect-selective neurotoxin, AaIT, which was
      isolated from the scorpion, Androctonus australis Hector. Two generalist
      predators, Chysoperla carnea Stephens and Orius insidiosus (Say), were not
      adversely affected by feeding on larvae of Heliothis virescens (F.) infected with
      AcAaIT. Similarly, no adverse effects were detected in the honey bee, Apis
      mellifera L., when injected with wild-type or recombinant NPVs. Results from this
      study may provide a foundation upon which potential risks associated with
      genetically engineered NPVs may be evaluated on a limited scale in greenhouse or
      field experiments.

PMID- 7722082
TI  - Increased efficacy of Bacillus thuringiensis subsp. kurstaki in combination with
      tannic acid.
AB  - We identified tannic acid as an inexpensive additive that increased the efficacy
      of sublethal concentrations of Bacillus thuringiensis subsp. kurstaki (Berliner).
      Tannic acid mimicked the active constituents contained in an aqueous, tannin-rich
      extract of Taxus baccata (L.) bark that retarded development of Heliothis
      virescens (F.) larvae at 10,000 ppm; most larvae remained in first and second
      stage when treated with 250-10,000 ppm of tannic acid. Instar development of
      Trichoplusia ni (Hubner) larvae was affected in a concentration-dependent manner
      by 2.5-500 ppm of tannic acid. In subsequent bioassays, tannic acid at 25-500 ppm
      in combination with B. thuringiensis (1.63 micrograms [AI]/ml diet) yielded mean
      mortalities of 57-75%, whereas treatments with B. thuringiensis alone produced
      10% mortality. Mean mortalities in the 3.0, 4.5, and 6.75 micrograms (AI) B.
      thuringiensis per milliliter of diet treatments (5.5; 8.0, and 30%, respectively)
      were significantly higher in the presence of 250 and 2,500 ppm tannic acid; in
      these treatments we observed 78-94% mortality. Addition of tannic acid increased
      the activity of concentrations of 3-4.5 micrograms (AI) B. thuringiensis per
      milliliter of diet to approximately that of a concentration of 13 micrograms (AI)
      B. thuringiensis per milliliter of diet alone (85-95% mortality). Although deaths
      caused by a formulation of B. thuringiensis + tannic acid occurred more slowly
      than with high rates of B. thuringiensis alone, such formulations would have the
      advantages of arresting development, minimizing foliar damage, and decreasing the
      concentration of B. thuringiensis used.

PMID- 7722083
TI  - Physiological responses of beef cattle to Gulf Coast tick (Acari: Ixodidae)
      infestations.
AB  - Nine yearling crossbred beef steers, Bos taurus L., were used to examine
      physiological responses to Gulf Coast tick, Amblyomma maculatum Koch,
      infestation. Steers were stanchioned indoors in individual environmentally
      controlled rooms. On day 0, each animal received 0, 25, or 75 pairs of ticks.
      Physiological variables measured daily were feed intake, heart rates, rectal
      temperatures, and respiration rates. Blood samples were collected from each
      animal on days 7, 21, and 42 for serum constituent analysis. To monitor metabolic
      hormone status, intensive blood samples were collected hourly for 6 h on days 21
      and 42. Throughout the treatment period, feed intake values were similar among
      treatments resulting in comparable body weight at the end of the trial. Heart
      rates and rectal temperatures were unaffected, however, respiration rates of
      steers infested with 25 pairs of ticks were higher than the other treatment
      groups. Treatment effects were detected in uric acid concentrations on day 7 in
      steers infested with 75 pairs of ticks. Treatment effects were detected in total,
      direct and indirect bilirubin, gamma-glutamyl transpeptidase, and aspartate amino
      transferase concentrations. Likewise, creatine kinase concentrations were higher
      in the tick-infested steers on day 7. Elevated white blood cell counts were
      observed in tick-infested steers. All other serum components were similar and
      were within their normal ranges. Serum insulin, prolactin, growth hormone, and
      cortisol concentrations were unaffected by tick infestations. Gulf coast tick
      infestation resulted in altered blood composition indicative of infection caused
      by tick feeding habits.

PMID- 7722084
TI  - A case of trichorrhexis nodosa developed in winter.
AB  - A young Japanese man developed localized trichorrhexis nodosa (LTN) of the scalp
      hair in the winter season. To investigate the roles of shampoo, severe sunlight
      exposure and/or mechanical injuries, we performed the following studies. Hair was
      collected from the patient and from a control. The study was performed in two
      steps. In the first step, hair was put into shampoo, rinsed with saline water,
      and then exposed to ultraviolet B (UVB) radiation once a day for one week. In the
      second step, the hair was similarly treated, but each shaft was bent gently with
      forceps before UVB exposure. Scanning electron microscopic studies revealed
      cuticular changes when the hair was treated only with shampoo and UVB. When it
      was treated with shampoo, UVB, and mechanical bending, the patient's hair
      developed longitudinal and transverse fractures of the hair shafts, while the
      control hair showed only partial damage to the hair shaft. On the basis on the
      above findings, we conclude that mechanical bending may damage the hair shaft.

PMID- 7722085
TI  - Basal cell carcinoma with eccrine differentiation.
AB  - We describe a light, electron microscopic, and immunohistochemical study of basal
      cell carcinoma with eccrine differentiation. The cytoplasm did not stain with fat
      stain on cryostat sections, but contained numerous gland-like structures.
      Immunohistochemistry on formalin fixed, paraffin embedded tissues using
      antibodies to human involucrin, thirteen kinds of cytokeratin, S-100 protein, and
      carcinoembryonic antigen (CEA) was performed. We found that tumor cells were
      positive for keratin, PKK1, MA-903, No 8, No 19, AE 1, AE 3, and 5 + 8. Tumor
      cells were negative for S-100 protein, CEA, and the other antigens examined.
      Electron microscopy demonstrated short microvilli and amorphous materials within
      the intracytoplasmic cavity. We concluded that this tumor is basal cell carcinoma
      with eccrine differentiation.

PMID- 7722086
TI  - Three cases of chemotherapy-induced acral erythema.
AB  - Three cases of chemotherapy-induced acral erythema are reported. All the patients
      had received cyclophosphamide, vincristine, adriamycin, prednisolone, and
      granulocyte-colony stimulating factor (G-CSF) for the treatment of leukemia or
      malignant lymphoma. From 35 to 45 days after the start of chemotherapy, painful
      erythematous lesions developed on their palms, soles, fingers, and toes,
      resulting in blister formation and desquamation. The recent higher incidence of
      chemotherapy-induced acral erythema may be correlated with the popularity of G
      CSF, which allows the use of higher doses of chemotherapeutic drugs.

PMID- 7722087
TI  - Remission of pustular psoriasis after cholecystectomy: role of focal infection in
      pustularization of psoriasis.
AB  - We report an 81-year-old male with long lasting psoriasis with exacerbation who
      showed remission of skin lesions after cholecystectomy. He consulted our clinic
      for impetiginous skin lesions and was treated with oral antibiotics without
      improvement. Several days later, he developed right hypochondralgia and was
      diagnosed with acute cholecystitis with gallstones. After cholecystectomy, the
      skin lesions significantly improved and disappeared within three weeks.
      Laboratory examination data indicated that acute inflammatory parameters
      normalized simultaneously. Although the role of focal infection in psoriasis is
      obscure, our case emphasizes the importance of focal infection in the
      pathogenesis of unstable psoriasis.

PMID- 7722088
TI  - Association of the acral type of pustular psoriasis, Sjogren's syndrome, systemic
      lupus erythematosus, and Hashimoto's thyroiditis.
AB  - We describe a case of a 53-year-old Japanese female suffering from Sjogren's
      syndrome, systemic lupus erythematosus, and Hashimoto's thyroiditis who developed
      pustules, erythema, and erosions on her fingers and toes. The histological
      specimen showed psoriatic changes. Indirect immunofluorescent study using anti
      human IL (interleukin)-8 antibody produced positive staining patterns in the
      lesional epidermis. These findings suggested the diagnosis of acral pustular
      psoriasis. Diaminodiphenylsulfone at 75 mg orally daily for 20 days and the
      application of 0.12% betamethasone valerate ointment led to gradual improvement.

PMID- 7722089
TI  - Melkersson-Rosenthal syndrome in India: experience with six cases.
AB  - Six patients with Melkersson-Rosenthal syndrome (M-R syndrome) were presented.
      Their ages varied from 20 to 60 years; age at onset was between 15 and 50 years.
      In all 6 patients, swelling started first over the lower lip. Associated facial
      palsy, facial edema, and scrotal tongue were found in three, four and one
      patients, respectively. Lip biopsies from 5 patients failed to show any
      granuloma. Intralesional corticosteroids produced mild regression of labial
      swelling in two patients after 6 injections. In one patient, near total reduction
      of labial swelling and facial edema was achieved after 5 months of clofazimine
      treatment. However, there was no improvement of facial palsy. To the best of our
      knowledge, this is the largest series of M-R syndrome reported from India.

PMID- 7722090
TI  - Tuberous sclerosis: unusual associations.

PMID- 7722091
TI  - Neutrophilic eccrine hidradenitis: report of two cases.
AB  - BACKGROUND: Neutrophilic eccrine hidradenitis (NEH) is an uncommon, self-limited
      dermatosis usually attributed to anti-cancer chemotherapy. It is characterized
      histologically by necrosis of the eccrine gland and neutrophilic infiltrate.
      OBSERVATIONS: We saw NEH in a 5-year-old boy with acute lymphoblastic leukemia
      and a 4-year-old girl with acute monocytic leukemia. NEH developed after the anti
      leukemic chemotherapy including high dose cytarabine. The eruption was composed
      of vesicles, papules, and plaques. CONCLUSIONS: Histological findings were
      compatible with those described in the literature. NEH in our two patients could
      be attributed to high doses of cytarabine.

PMID- 7722092
TI  - Erythema induratum with pulmonary tuberculosis: report of three cases.
AB  - Three cases of erythema induratum which occurred in the patients with pulmonary
      tuberculosis are described. The cutaneous lesions were violaceous, indurated
      nodules on both lower legs above the malleoli. Histologically, tuberculoid
      granuloma with caseation necrosis was found in one case; necrotizing vasculitis
      was the prominent finding in other two cases. The erythema induratum promptly
      responded to antituberculous therapy. We believe that, in light of these cases,
      the association between erythema induratum and infection with tubercle bacilli
      should be re-emphasized.

PMID- 7722093
TI  - Activity of eight fluoroquinolones against both methicillin-susceptible and 
      resistant Staphylococcus aureus isolated from skin infections.
AB  - The in vitro susceptibility of Staphylococcus aureus to eight fluoroquinolones,
      norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin,
      sparfloxacin, and nadifloxacin was established by agar dilution tests, 71
      isolates of methicillin-susceptible (MSSA) and 74 isolates of -resistant S.
      aureus (MRSA) isolated from skin infections. Among all of the fluoroquinolones,
      nadifloxacin exhibited the lowest MIC for both MSSA and MRSA. In addition, there
      were no resistant S. aureus, neither MSSA and MRSA, to nadifloxacin. With the
      exception of nadifloxacin, the incidence of MRSA resistant to fluoroquinolones
      has gradually increased in recent years. Over half of the MRSA strains were
      resistant to norfloxacin, ofloxacin, enoxacin, ciprofloxacin, and lomefloxacin.

PMID- 7722094
TI  - Polysialogangliosides expressed by amelanotic melanoma: a possible explanation
      for the poor response to anti-monosialoganglioside antibody 202 in a patient with
      melanoma.
AB  - A 52-year-old Japanese woman developed numerous amelanotic metastatic melanomas
      on the skin and in various organs three years after a surgical operation for
      primary melanoma on the right axilla. The patient was treated with
      monosialoganglioside specific monoclonal antibody 202; however, no apparent
      clinical effects were observed. Ganglioside analysis of a metastatic tumor
      demonstrated that it expressed GM3, GM2, GD3, GD2, and polysialogangliosides.
      Since polysialogangliosides rarely appear in melanomas, their expression may
      explain the patient's poor response to MAb 202. The relationship between
      ganglioside composition and the effect of anti-ganglioside monoclonal antibody is
      discussed.

PMID- 7722095
TI  - Cortisol status in different types of leprosy.
AB  - Basal plasma cortisol levels in 12 controls and 60 patients with different types
      of leprosy were within normal limits. They were significantly lower in
      multibacillary leprosy patients; this abnormality might be due to long standing
      stress leading to adrenal exhaustion. The plasma cortisol level significantly
      increased after the ACTH (Synacthen) stimulation test in all of the varieties of
      leprosy tested, which suggests that the adrenal reserve is maintained in such
      cases.

PMID- 7722096
TI  - A histological study of cutaneous thermal wounds using a Clostridium perfringens
      derived wound healing substance with wound healing stimulation activity.
AB  - We studied the effects of a Clostridium perfringens-derived wound-healing
      substance (WHS) on the healing of thermal burn wounds. Third-degree burn injuries
      were inflicted on the back skin of rats. We histologically evaluated the effects
      of WHS ointments and compared them with those of lysozyme chloride ointment. We
      observed the formation of dermal collagen fibers and the increase of capillaries
      in the WHS ointment treated groups. From the results of hematoxylin and eosin
      staining and silver staining, an increase in capillaries was observed one week
      after the application of WHS ointment. Three weeks after the application, when
      the epithelization was in the final stage, capillary formation ceased. In the WHS
      ointment-applied groups, electron microscopic observation showed that new
      collagen fibers were regularly formed in the dermis. On the other hand, in the
      lysozyme chloride ointment-applied groups, new collagen fibers were present, but
      were irregularly formed. The main wound healing stimulative action of the WHS
      ointment could be due to its acceleration of new capillary formation.

PMID- 7722097
TI  - Defining 'reportable events'.

PMID- 7722098
TI  - Economical continuing education.

PMID- 7722099
TI  - Dental technology: help or hazard?

PMID- 7722100
TI  - Bonding amalgams: use with care.

PMID- 7722101
TI  - Looking at the future of lasers.

PMID- 7722102
TI  - Understanding managed care.

PMID- 7722103
TI  - A look at legal issues in managed care, marketplace change.

PMID- 7722104
TI  - Managed care and dentistry: promises and problems.
AB  - At its inception in the mid-1950s, managed care held a number of promises for
      dental care providers and dental patients. Sometime during the development of
      managed care, however, many programs lost sight of the importance of provider
      equity. Using data from current programs, the authors contrast the original
      promises with the realities of managed care in dentistry.

PMID- 7722105
TI  - How fee and insurance changes could affect dentistry: results from a
      microsimulation model.
AB  - Dentists have become concerned about the possible impact of reductions in dental
      insurance coverage. The authors used a microsimulation model of the dental sector
      to assess the potential impact of reductions in the percentage of Americans with
      dental insurance, in universal dental insurance coverage for children and in fees
      paid to dentists for their services. The model predicted that reductions in
      dental insurance coverage would reduce per capita dental expenditures, but that
      the impact would not be large. Fee reductions had the greatest impact on dental
      expenditures of any change simulated by the model.

PMID- 7722106
TI  - Treating obstructive sleep apnea: can an intraoral prosthesis help?
AB  - The author studied the effectiveness of an intraoral airway maintenance
      prosthesis in treating obstructive sleep apnea syndrome. He found that the
      prosthesis, which can be constructed and modified easily by a dentist,
      significantly reduced the number of apneas per night and the syndrome's severity
      in his subjects.

PMID- 7722107
TI  - Managing periorbital space abscess. Secondary to dentoalveolar abscess.
AB  - Although orbital space infections are a relatively rare sequela of dentoalveolar
      infections, such cases have been reported. This case report describes the
      management of an abscess involving the left eye that originated as a dental
      abscess.

PMID- 7722108
TI  - The endodontic-periodontal lesion: a rational approach to treatment.
AB  - When a periapical lesion communicates with a deep periodontal pocket, the
      etiology can be either endodontic or periodontal. This article clarifies the
      relationship between pulpal and periodontal disease and presents a systematic
      approach to the diagnosis and management of endodontic-periodontal lesions. It
      also presents a case that demonstrates the successful treatment of teeth that
      appear to be hopelessly diseased.

PMID- 7722109
TI  - Transplanting teeth successfully: autografts and allografts that work.
AB  - This article suggests tooth transplantation as an alternative to other
      restorative options. The 10-year success rates for autografts--teeth moved from
      one location to another in a patient's mouth--range from 60 percent to 95
      percent. Allografts, teeth moved from one person to another, are less successful.
      The authors report on one case of each type of transplant.

PMID- 7722110
TI  - Cementing resin-bonded fixed partial dentures: a simplified technique.

PMID- 7722111
TI  - The incidence of orofacial injuries in sports: a pilot study in Illinois.
AB  - This pilot study of sports-related injuries in Illinois confirms that football
      players do not encounter orofacial injuries as often as other athletes. The
      authors attribute this to mandatory use of faceguards and mouth protectors in
      football and recommend that mouthguards be used by all players of contact sports.

PMID- 7722112
TI  - Relining, rebasing partial and complete dentures.

PMID- 7722113
TI  - Dentists' attitudes toward the treatment of HIV-positive patients.
AB  - The authors studied the attitudes of 1,000 U.S. dentists toward the treatment of
      HIV-positive patients. Using a random-sample mail survey, they measured dentists'
      professional attitudes toward treating HIV/AIDS patients, fear of contagion and
      negative emotions toward HIV-positive patients. The results indicate that 68
      percent of the respondents would treat an HIV-positive patient, even if the
      possibility for a legitimate referral exists.

PMID- 7722114
TI  - Carvedilol improves left ventricular function and symptoms in chronic heart
      failure: a double-blind randomized study.
AB  - OBJECTIVES: This study assessed the safety and efficacy of carvedilol in patients
      with heart failure caused by idiopathic or ischemic cardiomyopathy. BACKGROUND:
      Carvedilol is a mildly beta 1-selective beta-adrenergic blocking agent with
      vasodilator properties. Beta-blockade may be beneficial in patients with heart
      failure, but the effects of carvedilol are not known. METHODS: Sixty patients
      with heart failure (New York Heart Association functional classes II to IV) and
      left ventricular ejection fraction < or = 0.35 were enrolled in the study. All
      patients tolerated challenge with carvedilol, 3.125 mg twice a day, and were
      randomized to receive carvedilol (n = 36) versus placebo (n = 24). Study
      medication was titrated over 1 month from 6.25 to 25 mg twice a day (< 75 kg) or
      50 mg twice a day (> 75 kg) and continued for 3 months. One placebo-treated and
      two carvedilol-treated patients did not complete the study. RESULTS: Carvedilol
      therapy resulted in a significant reduction in heart rate and mean pulmonary
      artery and pulmonary capillary wedge pressures and a significant increase in
      stroke volume and left ventricular stroke work. Left ventricular ejection
      fraction increased 52% in the carvedilol group (from 0.21 to 0.32, p < 0.0001 vs.
      placebo group). Carvedilol-treated patients also reported a significant lessening
      of heart failure symptoms (p < 0.05 vs. placebo group). Submaximal exercise
      duration tended to increase with carvedilol therapy (from 688 +/- 31 s to 871 +/-
      32 s), but this change was not significantly different from that with placebo
      therapy by between-group analysis. Peak oxygen consumption during maximal
      exercise did not change. CONCLUSIONS: Long-term carvedilol therapy improves rest
      cardiac function and lessens symptoms in patients with heart failure.

PMID- 7722115
TI  - Exercise intolerance in chronic heart failure is not associated with impaired
      recovery of muscle function or submaximal exercise performance.
AB  - OBJECTIVES: This study investigated whether recovery of skeletal muscle function
      is impaired in patients with heart failure and whether impaired recovery is
      associated with abnormal submaximal systemic exercise tolerance during repeated
      testing. BACKGROUND: Patients with heart failure experience fatigue during daily
      activities. Because abnormalities of skeletal muscle play a role in their
      exercise intolerance, these symptoms may reflect a delay in muscle recovery and a
      resulting limitation in submaximal exercise tolerance. METHODS: Two protocols
      were used. In protocol 1, knee extensor strength and endurance, and their
      recovery after fatiguing exercise, were evaluated in 11 patients (mean [+/- SEM]
      age 62 +/- 5 years, New York Heart Association functional class 2.3 +/- 0.2,
      ejection fraction 24 +/- 5%) and in 10 age-matched sedentary control subjects.
      Protocol 2 examined the recovery of knee extensor endurance and submaximal
      exercise tolerance, as quantified on a self-powered treadmill, over 24 h in 18
      patients (mean age 65 +/- 3 years, functional class 2.4 +/- 0.2, ejection
      fraction 23 +/- 3%) and in 10 control subjects. RESULTS: Peak oxygen consumption
      was reduced in both heart failure groups (15.4 +/- 1.4 and 15.6 +/- 1.0 ml/kg per
      min) compared with that in the respective control groups (23.1 +/- 2.9 and 25.6
      +/- 1.0 ml/kg per min, both p < 0.05), as was muscle endurance but not muscle
      strength. In protocol 1, knee extensor endurance recovered more slowly in the
      patients than in control subjects (to 62 +/- 4% and 87 +/- 7% of the baseline
      value after 5 min, respectively, p < 0.05). In protocol 2, submaximal exercise
      tolerance was lower in the patients with heart failure than in control subjects
      (1,075 +/- 116 vs. 1,390 +/- 110 m), but knee extensor endurance and walking
      distance recovered fully by 10 and 30 min, respectively. CONCLUSIONS: Although
      these findings confirm earlier studies that demonstrated impaired muscle
      endurance in patients with heart failure, the results provide no evidence that
      recovery of either muscle function or submaximal exercise tolerance is delayed
      beyond the initial 5 to 10 min after exercise.

PMID- 7722116
TI  - Physical training in patients with stable chronic heart failure: effects on
      cardiorespiratory fitness and ultrastructural abnormalities of leg muscles.
AB  - OBJECTIVES: The present study was designed to evaluate the effect of an
      ambulatory training program on ultrastructural morphology and the oxidative
      capacity of skeletal muscle and its relation to central and peripheral
      hemodynamic variables in patients with chronic heart failure. BACKGROUND:
      Clinical evidence supports the hypothesis that exercise intolerance in patients
      with chronic heart failure is not only a consequence of low cardiac output, but
      is also a result of alterations in oxidative metabolism of skeletal muscle.
      METHODS: Twenty-two patients were prospectively randomized either to a training
      group (mean [+/-SD] ejection fraction 26 +/- 9%, n = 12) participating in an
      ambulatory training program or to a physically inactive control group (ejection
      fraction 27 +/- 10%, n = 10). At baseline and after 6 months, patients underwent
      symptom-limited bicycle exercise testing, and central and peripheral hemodynamic
      variables were measured. Percutaneous needle biopsy samples of the vastus
      lateralis muscle were obtained at baseline and after 6 months. The ultrastructure
      of skeletal muscle was analyzed by ultrastructural morphometry. RESULTS: After 6
      months, patients in the training group achieved an increase in oxygen uptake at
      the ventilatory threshold of 23% (from 0.86 +/- 0.2 to 1.07 +/- 0.2 liters/min, p
      < 0.01 vs. control group) and at peak exercise of 31% (from 1.49 +/- 0.4 to 1.95
      +/- 0.4 liters/min, p < 0.01 vs. control group). There was no significant change
      in oxygen uptake at the ventilatory threshold and at peak exercise in the control
      group. The total volume density of mitochondria and volume density of cytochrome
      c oxidase-positive mitochondria increased significantly by 19% (from 4.7 +/- 1.5
      to 5.6 +/- 1.5 vol%, p < 0.05 vs. control group) and by 41% (from 2.2 +/- 1.0 to
      3.1 +/- 1.0 vol%, p < 0.05 vs. control group) after 6 months of regular physical
      exercise. Cardiac output at rest and at submaximal exercise remained unchanged
      but increased during maximal symptom-limited exercise from 11.9 +/- 4.0 to 14.1
      +/- 3.3 liters/min in the training group (p < 0.05 vs. baseline; p = NS vs.
      control group). Peak leg oxygen consumption increased significantly by 45% (from
      510 +/- 172 to 740 +/- 254 ml/min, p < 0.01 vs. control group). Changes in
      cytochrome c oxidase-positive mitochondria were significantly related to changes
      in oxygen uptake at the ventilatory threshold (r = 0.82, p < 0.0001) and at peak
      exercise (r = 0.87, p < 0.0001). CONCLUSIONS: Regular physical training increases
      maximal exercise tolerance and delays anaerobic metabolism during submaximal
      exercise in patients with stable chronic heart failure. Improved functional
      capacity is closely linked to an exercise-induced increase in the oxidative
      capacity of skeletal muscle.

PMID- 7722117
TI  - Relations between heart failure, ejection fraction, arrhythmia suppression and
      mortality: analysis of the Cardiac Arrhythmia Suppression Trial.
AB  - OBJECTIVES: We studied the relations between heart failure, ejection fraction,
      arrhythmia suppression and mortality. BACKGROUND: Both left ventricular ejection
      fraction and functional class of heart failure are strongly associated with
      mortality after acute myocardial infarction. Both are also related to the
      presence of ventricular arrhythmias and have been identified as factors related
      to the ability to suppress ventricular arrhythmias. Little has been reported
      about the relations between these two factors and arrhythmia suppression or
      mortality. METHODS: Baseline data from the Cardiac Arrhythmia Suppression Trial
      were used to define several categories of heart failure and to relate both the
      resulting categories and ejection fraction to arrhythmia suppression and
      mortality using logistic and survival regression analytic methodologies. RESULTS:
      Regardless of the prospective baseline definition of heart failure used, the data
      consistently showed that heart failure was a more powerful predictor of
      subsequent congestive heart failure events and arrhythmia suppression and was
      equally powerful in predicting death. However, each variable provided incremental
      information when included in the prediction model. Heart failure and ejection
      fraction appeared to be independent predictors of death. Interactions were
      observed: A low ejection fraction was more predictive of failure of arrhythmia
      suppression in patients with than without evidence of heart failure before or at
      baseline; a low ejection fraction was more predictive of subsequent congestive
      heart failure events in patients without than with evidence of heart failure
      before or at baseline. CONCLUSIONS: Although heart failure as a prognostic
      feature appears to be somewhat superior to ejection fraction, both are powerful
      predictors of arrhythmia suppression and cardiac events in patients with
      ventricular arrhythmia after myocardial infarction. Each provides incremental
      prediction.

PMID- 7722118
TI  - Heterogeneity of ventricular function and myocardial oxidative metabolism in
      nonischemic dilated cardiomyopathy.
AB  - OBJECTIVES: This study was performed to test the hypothesis that regional
      variation in ventricular function in patients with nonischemic dilated
      cardiomyopathy is related to regional variation in oxidative metabolism.
      BACKGROUND: Heterogeneity in regional left ventricular function has long been
      noted in patients with nonischemic dilated cardiomyopathy. Regional variation in
      wall stress has been proposed as the pathophysiologic mechanism. By correlating
      regional function with oxidative metabolism, one can test the hypothesis that
      heterogeneity in wall stress is responsible for heterogeneity in function. We
      hypothesized that preserved function as a result of more favorable loading
      conditions would be associated with regional oxidative metabolism that is equal
      to or lower than that in other regions. METHODS: Fifteen patients with
      nonischemic dilated cardiomyopathy (mean [+/- SD] ejection fraction 20.7 +/-
      4.0%) were studied. Regional ventricular function was determined using short-axis
      chordal shortening on two-dimensional echocardiography. Regional oxidative
      metabolism was assessed by carbon-11 acetate clearance kinetics on dynamic
      positron emission tomography. An eight-segment model of the left ventricle was
      used. Segmental function and oxidative metabolism were defined as increased if
      they varied at least 1 SD from the respective mean value for that patient.
      RESULTS: Thirteen (87%) of 15 patients exhibited segments with increased
      function. In 7 (54%) of 13 patients, regional function was increased in the
      proximal lateral wall. Multivariate linear regression analysis showed a direct
      relation between regional function and oxidative metabolism (p = 0.02). The
      average concordance between increased function and increased oxidative metabolism
      among patients was 0.87 +/- 0.11 (95% confidence interval 0.70 to 1.00).
      CONCLUSIONS: Patients with nonischemic dilated cardiomyopathy display
      heterogeneity in regional ventricular function. Relative preservation is observed
      most frequently in the proximal lateral wall. Relative preservation of function
      is associated with higher regional oxidative metabolism, suggesting that
      mechanisms other than or in addition to local loading conditions may be
      responsible for heterogeneity in function.

PMID- 7722119
TI  - Dilated cardiomyopathy is associated with an increase in the type I/type III
      collagen ratio: a quantitative assessment.
AB  - OBJECTIVES: The aim of this study was to quantify total collagen and the type
      I/type III collagen ratio and their localization in hearts with dilated
      cardiomyopathy. BACKGROUND: Patients with dilated cardiomyopathy have an increase
      in intramyocardial fibrillar collagen. Types I and III are the main constituents
      and have different physical properties that may affect cardiac compliance.
      METHODS: Nineteen hearts with dilated cardiomyopathy were studied (17 cardiac
      explants, 2 hearts obtained at autopsy) and compared with reference hearts. Total
      collagen was determined by hydroxyproline analysis. Collagen types I and III were
      analyzed using the cyanogen bromide method and immunohistochemical analysis
      followed by microdensitophotometric quantification. Localization of collagen
      types I and III was established at the light and electron microscopic levels.
      Immunoelectron microscopy provided information regarding their localization.
      RESULTS: Total collagen and the collagen type I/type III ratio were increased in
      hearts with dilated cardiomyopathy (p < 0.05). Electron microscopy showed a
      diffuse increase in collagen fibrils in the endomysium; the perimysium showed an
      inhomogeneous increase. Collagen fibrils were thicker, and fibrous long-spacing
      collagen occurred in the endomysium. Immunoelectron microscopic findings
      confirmed an increase in type I collagen. CONCLUSIONS: Hearts with dilated
      cardiomyopathy have a statistically significant increase in the collagen type
      I/type III ratio. The changes occur in the endomysium and perimysium, although
      with differences in distribution. These changes in intramyocardial collagen may
      be clinically relevant because they may affect cardiac rigidity and, therefore,
      eventually may render the heart less compliant. Further studies are needed to
      evaluate at what point in the course of the disease these changes appear.

PMID- 7722120
TI  - Renal response to candoxatrilat in patients with heart failure.
AB  - OBJECTIVES: Our primary objective was to compare the effects of three different
      doses of candoxatrilat with the effects of placebo on urinary volume in patients
      with moderately severe heart failure. The effects of candoxatrilat on urinary
      composition, neuroendocrine indexes and renal hemodynamic function were also
      studied. BACKGROUND: Candoxatrilat, a neutral endopeptidase inhibitor, reduces
      degradation of atrial natriuretic peptide and provokes diuresis in patients with
      mild heart failure, but the renal effects have not been studied in patients with
      moderately severe heart failure in a placebo-controlled study. METHODS: In a
      double-blind crossover trial, the effects of intravenous boluses of saline
      vehicle (placebo) and 50, 100 and 200 mg of candoxatrilat were compared on
      separate days in 12 patients with heart failure. Urinary output and composition
      were measured for 8 h. Renal blood flow and glomerular filtration rate were
      determined by radionuclide techniques. Blood was withdrawn for the measurement of
      hormones before and 3 h after dosing. RESULTS: All doses of candoxatrilat
      increased urinary volume (e.g., [mean +/- SEM] 263 +/- 53 to 490 +/- 82 ml for
      saline solution and the 200-mg dose, respectively, p < 0.01) and sodium content
      (14 +/- 4 to 37 +/- 11 mmol, p < 0.001) in the 1st 4 h after dosing. Plasma
      atrial natriuretic peptide increased (140 +/- 26 to 279 +/- 37 pg/ml, p < 0.01),
      whereas aldosterone decreased (178 +/- 41 to 125 +/- 35 pg/ml, p < 0.01), and
      renin activity was unchanged (10 +/- 2 to 12 +/- 3 ng/ml per h). CONCLUSIONS:
      Candoxatrilat given acutely causes diuresis, even in patients with moderately
      severe heart failure.

PMID- 7722121
TI  - Angioscopic identification of coronary thrombus in patients with postinfarction
      angina.
AB  - OBJECTIVES: The purpose of this study was to determine the prevalence of
      intracoronary thrombus and associated anatomic abnormalities in patients with
      postinfarction angina using coronary angioscopy and angiography. BACKGROUND:
      Postinfarction angina, previously studied by angiographic methods only,
      identifies patients at high risk for sudden death, recurrent angina and
      refractory angina. The recent development of coronary angioscopy, which permits
      direct observation of a thrombus or atheroma and is especially used for the
      detection of intraluminal changes, encourages a reexamination of the pathogenesis
      of postinfarction angina. METHODS: Fifty-one consecutive patients with a
      diagnosis of acute myocardial infarction underwent cardiac catheterization.
      Coronary angiography followed immediately by coronary angioscopy was performed in
      17 patients with and 34 without postinfarction angina during the same period of
      time (10.2 +/- 3.7 or 15.7 +/- 5.5 days [mean +/- SD]) after the onset of acute
      myocardial infarction. RESULTS: The frequency of thrombus, as observed by
      angioscopy, was significantly higher in patients with than without postinfarction
      angina (17 of 17 vs. 5 of 34, respectively, p < 0.01). There were no significant
      differences between groups with respect to degree of stenosis in the infarct
      related artery, number of vessels with significant stenosis, presence of
      collateral flow, type of therapy and risk factors. CONCLUSIONS: Infarct-related
      artery thrombus is universally present in postinfarction angina and may be the
      primary pathogenic factor. Angioscopy is much more sensitive than coronary
      angiography for the detection of coronary thrombus.

PMID- 7722122
TI  - Incidence and follow-up of Braunwald subgroups in unstable angina pectoris.
AB  - OBJECTIVES: This study was performed to establish the prognosis of patients with
      unstable angina within the subgroups of the Braunwald classification. BACKGROUND:
      Among many classifications of unstable angina, the Braunwald classification is
      frequently used. However, the incidence and risk for each subgroup in clinical
      practice have not been established. METHODS: Prospective data for 417 consecutive
      patients admitted for suspected unstable angina were analyzed. Patients were
      classified according to Braunwald criteria and followed up for 6 months.
      Survival, infarct-free survival and infarct-free survival without intervention
      are reported for each class. RESULTS: After in-hospital observation the final
      diagnosis was acute myocardial infarction in 26 patients (6%), noncoronary chest
      pain in 109 (26%) and definite unstable angina in 282 (68%). Recurrence of chest
      pain was significantly different for the different severity classes (28%, 45% and
      64% for classes I [accelerated angina], II [subacute angina at rest] and III
      [acute angina at rest], respectively) but not for clinical circumstances (49% and
      53% for classes B [primary unstable angina] and C [postinfarction unstable
      angina], respectively). Six-month and infarct-free survival (96% and 88%,
      respectively) were not significantly different between severity classes but were
      significantly different (p = 0.01) between classes B (97% and 89%) and C (89% and
      80%). Infarct-free survival without intervention was best for class II (72%),
      intermediate for class I (53%) and worst for class III (35%). In multivariate
      analysis, elderly age, male gender, hypertension, class C and maximal
      (intravenous) therapy were independent predictors for death; elderly age and
      class C for infarct-free survival; and male gender, class III, class C,
      electrocardiographic changes and maximal therapy were associated with infarct
      free survival without intervention. CONCLUSIONS: Braunwald classification is an
      appropriate instrument to predict outcome. Risk stratification by these criteria
      provides a tool for patient selection in clinical trials and for evaluation of
      treatment strategies.

PMID- 7722123
TI  - Toward a stable clinical classification of unstable angina.

PMID- 7722124
TI  - Effectiveness of prolonged low dose recombinant tissue-type plasminogen activator
      for refractory unstable angina.
AB  - OBJECTIVES: The aim of the present study was to evaluate the effectiveness of
      prolonged administration of thrombolytic therapy with low doses of recombinant
      tissue-type plasminogen activator (rt-PA) in patients with refractory unstable
      angina. BACKGROUND: Intracoronary thrombosis is often the cause of instability in
      patients with unstable angina. Thrombolytic therapy has been tested in these
      patients with conflicting results. METHODS: Sixty-seven patients with unstable
      angina refractory to standard antianginal therapy were randomized to receive, in
      addition to the common antianginal therapy, either rt-PA (0.03 mg/kg body weight
      per h for 3 consecutive days) plus heparin (to achieve activated clotting time of
      250 to 400 s) (36 patients, group A) or the same dose of heparin plus placebo (31
      patients, group B). RESULTS: No major bleeding was observed in either group of
      patients. One patient in group A and four in group B (2.7% vs. 12.9%, p < 0.01)
      developed acute myocardial infarction during the hospital period. Eight patients
      in group B underwent emergency coronary artery surgery or angioplasty because of
      worsening of symptoms. Group A patients had a significant reduction in the
      occurrence of chest pain compared with those in group B (95% confidence interval 
      7.2 to -2.1 episodes/3 days, p < 0.01). Patients in group B had a greater number
      of episodes of transient myocardial ischemia (237 vs. 103, p < 0.01) and a longer
      total ischemic burden (114 +/- 23 vs. 45.6 +/- 8.9 min/day, p < 0.01) than group
      A patients. After a mean follow-up of 14 +/- 6 months, group A patients were more
      frequently angina free and had a lower incidence of readmission to the hospital
      than group B patients. CONCLUSIONS: The combination of heparin and protracted
      administration of rt-PA at low doses is effective in stabilizing and reducing in
      hospital adverse events in patients with unstable angina refractory to
      antianginal therapy.

PMID- 7722125
TI  - Adenosine combined with dynamic exercise for myocardial perfusion imaging.
AB  - OBJECTIVES: This study investigated whether combining exercise with adenosine
      would reduce the adverse effects of adenosine vasodilation. BACKGROUND: Adenosine
      vasodilation is effective for perfusion imaging but causes frequent unpleasant
      noncardiac adverse effects, high noncardiac tracer uptake and occasional
      arrhythmias. METHODS: Of 500 consecutive patients referred for thallium-201
      myocardial perfusion imaging, 407 were randomized to three study groups: 6 min of
      adenosine infusion alone; 6 min of adenosine with submaximal exercise; or symptom
      limited exercise with continuous adenosine. Minimal detectable differences are
      presented; a significance level of 0.05 with a power of 80% is assumed. RESULTS:
      There was no difference among the three groups in sensitivity and specificity
      (overall 96% and 78%, minimal detectable differences 5.5% and 11%, respectively)
      for detection of coronary artery disease or stenosis in individual coronary
      arteries. There was a trend toward improved sensitivity in the combined exercise
      groups compared with that in the adenosine-only group (98% vs. 93%, p = 0.07,
      minimal detectable difference 6%). Noncardiac side effects were reduced by 43% in
      the exercise groups (p < 0.0001), and major arrhythmias were reduced by 90% (p <
      0.0001). There was no effect on minor arrhythmias (25% vs. 22%, p = 0.6, minimal
      detectable difference 12%). The heart/background ratios were higher in the
      exercise groups (all p < 0.02). Each ratio was correlated with the exercise level
      achieved (all p < 0.001). The reversibility score increased with exercise (p =
      0.04), as did the number of patients and segments with reversible defects (both p
      = 0.03). CONCLUSIONS: Combining exercise with adenosine infusion reduced the
      noncardiac side effects of vasodilation and major arrhythmias while improving
      redistribution and heart/background ratios. These findings may be clinically
      important. Although maximal exercise with adenosine infusion produced optimal
      results, the improvement over the submaximal exercise protocol was minor, and
      this has the advantage of being simple and achievable within the normal 6-min
      duration of the adenosine infusion.

PMID- 7722126
TI  - Anatomic and physiologic heterogeneity in patients with syndrome X: an
      intravascular ultrasound study.
AB  - OBJECTIVES: We used intravascular ultrasound imaging of the epicardial vessels to
      assess coronary morphology, vasomotor response to exercise and exercise
      vasomotion after beta-adrenoceptor blockade in patients with syndrome X.
      BACKGROUND: Syndrome X is defined as chest pain, abnormal exercise test results
      and normal coronary angiographic findings. Because of the limitations of coronary
      angiography, intravascular ultrasound was used to define coronary
      pathophysiology. METHODS: Thirty patients with syndrome X were studied with
      intravascular ultrasound imaging (30 MHz, 4.3F catheter) of all three major
      epicardial vessels. Supine arm exercise was performed during coronary imaging.
      Lumen area was assessed at rest and during peak exercise. The exercise-imaging
      protocol was repeated after loading with 0.1 mg/kg body weight of intravenous
      propranolol. RESULTS: Three morphologic groups were identified using
      intravascular ultrasound: normal coronary arteries (no plaque, intimal thickness
      < 0.25 mm, n = 12), atheromatous disease (mean [+/- SD] area stenosis 37.9 +/-
      7.2%, n = 10) and marked intimal thickening (0.73 +/- 0.11 mm, n = 8). Patients
      with normal coronary arteries displayed a vasodilatory response to exercise
      (+16.9% area increase); patients with abnormal coronary arteries displayed a
      vasoconstrictive response to exercise (-17.4% in the group with plaque; -17.6% in
      the group with intimal thickening). Propranolol loading attenuated the
      vasodilatory response in the group with normal coronary arteries (+6.4% area
      increase) and attenuated the vasoconstrictive response in the two groups with
      abnormal coronary arteries (-8.0% in the group with plaque; -8.8% in the group
      with intimal thickening). CONCLUSIONS: Most patients with syndrome X have
      abnormal coronary arteries by intravascular ultrasound. Intravascular ultrasound
      identifies three distinct morphologic groups: normal coronary arteries,
      atheromatous plaque and intimal thickening. Exercise-vasomotion is normal in
      patients with syndrome X who have normal coronary arteries by ultrasound;
      patients with abnormal arteries (plaque or intimal thickening) have an abnormal
      (constrictive) response to exercise. Propranolol loading attenuates
      vasoreactivity in all subgroups, suggesting divergent therapeutic utility.

PMID- 7722127
TI  - The continuing conundrum of syndrome X: further evidence of heterogeneity.

PMID- 7722128
TI  - ST segment and T wave characteristics as indicators of coronary heart disease
      risk: the Zutphen Study.
AB  - OBJECTIVES: This study evaluated the predictive value of T wave amplitude and ST
      segment level on lead I for angina pectoris, a first myocardial infarction,
      sudden death and coronary heart disease death in middle-aged and elderly men.
      BACKGROUND: Certain ST-T wave characteristics may reflect favorable autonomic
      cardiac control. Slight ST segment elevation has been reported to indicate a low
      risk of coronary heart disease mortality. METHODS: A total of 876 men, born
      between 1900 and 1920, participated in periodic medical examinations and were
      followed up with respect to morbidity and mortality from 1960 to 1985. In 1985,
      the remaining cohort was extended to 836 elderly men from the same birth cohort
      who were followed up until 1990. Relative risks in categories of T wave amplitude
      and ST segment level were estimated by survival analysis. RESULTS: Both middle
      aged and elderly men with T wave amplitudes > or = 0.15 mV had a lower risk of
      myocardial infarction, coronary heart disease death and sudden death than men
      with T wave amplitudes 0.05 to 0.15 mV. The adjusted relative risk of coronary
      heart disease death was 0.5 (95% confidence interval [CI] 0.2 to 1.0); in men
      with T wave amplitude < or = 0.05 mV, relative risk was 2.0 (95% CI 1.3 to 3.1).
      Slight ST segment elevation was also associated with decreased risk: relative
      risk 0.5 (95% CI 0.3 to 1.0) compared with the isoelectric ST segment level. In
      men with ST segment depression, relative risk was 2.2 (95% CI 1.4 to 3.4). The
      association of T wave amplitude and ST segment level were independent of each
      other. CONCLUSIONS: In addition to the elevated risk of coronary heart disease
      that is associated with ST-T wave abnormalities, we observed that normal
      variations in repolarization characteristics are predictive of future heart
      disease.

PMID- 7722129
TI  - Treatment with beta-adrenergic blocking agents after myocardial infarction: from
      randomized trials to clinical practice.
AB  - OBJECTIVES: Our aim was to determine the percent of patients with myocardial
      infarction who are treated with beta-adrenergic blocking agents in dosages proved
      to be effective in preventing death after a heart attack. BACKGROUND: In the
      prospective randomized trials showing that beta-blocker treatment improves
      survival rates after myocardial infarction, relatively high dosages of these
      agents were used. However, it is not known whether these dosages are used in
      current clinical practice. METHODS: In a retrospective analysis of clinical data
      from 606 consecutive survivors of myocardial infarction at four university
      hospitals in three countries, we assessed the number of infarct survivors
      receiving prospectively defined "effective dosages" of beta-blockers. We defined
      these dosages as those that demonstrated improved survival rates of infarct
      survivors who received active drug in large, prospective, double-blind, placebo
      controlled trials. RESULTS: Only 58% of infarct survivors with no
      contraindications to beta-blockers received these drugs at the time of hospital
      discharge, and only 11% received dosages equivalent to > 50% of the effective
      dosages. Independent predictors of failure to prescribe beta-blockers to infarct
      survivors without contraindications to these drugs were the use of diuretic
      agents, transient heart failure, impaired left ventricular function and increased
      patient age. Among patients receiving beta-blockers, only the use of propranolol
      predicted prescription of a low beta-blocker dosage. CONCLUSIONS: Failure to
      prescribe beta-blockers after myocardial infarction is common but in most cases
      is not due to clear contraindications. Many patients not receiving beta-blockers
      belong to subgroups that would derive the greatest benefit from such treatment.
      Finally, even when beta-blockers are prescribed, the dosages used are
      considerably lower than those proved to be effective in preventing death after
      myocardial infarction.

PMID- 7722130
TI  - Role of adenosine thallium-201 tomography for defining long-term risk in patients
      after acute myocardial infarction.
AB  - OBJECTIVES: This study prospectively evaluated whether early assessment with
      adenosine thallium-201 tomography could better refine risk stratification on the
      basis of absolute extent of myocardial ischemia in postinfarction patients in
      clinically stable condition. BACKGROUND: Postinfarction patients are at increased
      risk for subsequent cardiac events. However, identifying high risk patients among
      those with residual myocardial ischemia is suboptimal. METHODS: All 146 patients
      enrolled underwent assessment of left ventricular function and had adenosine
      tomography performed early (mean [+/- SD] 5 +/- 3 days) after infarction.
      Excluded from analysis were 51 patients with revascularization after scintigraphy
      and 3 lost to follow-up. Statistical risk models were therefore generated from
      the remaining 92 patients. RESULTS: Cardiac events occurred in 30 (33%) of 92
      patients over 15.7 +/- 4.9 months. Univariate predictors of all events were
      quantified perfusion defect size (p < 0.0001), absolute extent of left
      ventricular ischemia (p < 0.000001) and ejection fraction (p < 0.0001). Risk was
      best predicted by Cox analysis on the basis of 1) absolute extent of ischemia and
      ejection fraction (chi-square 24.6); 2) percent infarct zone ischemia and
      ejection fraction (chi-square 24.4); or 3) total perfusion defect size and
      percent infarct zone ischemia (chi-square 18.9). The variables that predicted all
      cardiac events were equally powerful at predicting only death and nonfatal
      reinfarction. Death was best predicted by total perfusion defect size.
      CONCLUSIONS: Risk analysis of individual patients early after infarction is
      feasible on the basis of the quantified extent of scintigraphic ischemia and
      severity of left ventricular dysfunction.

PMID- 7722131
TI  - Doppler left ventricular flow pattern versus conventional predictors of left
      ventricular thrombus after acute myocardial infarction.
AB  - OBJECTIVES: The value of Doppler-derived left ventricular spatial flow patterns
      in predicting left ventricular thrombus formation after myocardial infarction was
      compared with that of conventional clinical and echocardiographic variables.
      BACKGROUND: Assessment of left ventricular thrombosis risk after myocardial
      infarction is important because of potential embolic sequelae that are reduced by
      oral anticoagulant agents. METHODS: Clinical, two-dimensional and Doppler
      echocardiographic data were prospectively obtained in 104 patients with acute
      myocardial infarction within 48 h of admission. Ventricular flow was assessed by
      Doppler echocardiography and considered normal when brisk ventricular inflow with
      simultaneous onset at the mitral valve and apical levels was present, together
      with alternating directions of apical flow throughout the cardiac cycle. In
      addition to normal flow, two abnormal flow patterns were recognized: apical
      rotating flow and vortex ring formation. Oral anticoagulant agents were
      prescribed only to patients with abnormal flow at admission. The incidence of
      left ventricular thrombosis was assessed by echocardiography during 9 months of
      follow-up. RESULTS: Abnormal flow pattern had a positive predictive value of 63%
      and a negative predictive value of 99%. On stepwise logistic regression analysis,
      only abnormal flow pattern had an independent relation to left ventricular
      thrombus (odds ratio 92). CONCLUSIONS: Left ventricular flow pattern derived by
      Doppler echocardiography soon after admission is superior to conventional
      clinical and two-dimensional echocardiographic assessment in estimating the risk
      of left ventricular thrombosis after myocardial infarction.

PMID- 7722132
TI  - Efficacy and tolerability of transvenous low energy cardioversion of paroxysmal
      atrial fibrillation in humans.
AB  - OBJECTIVES: This study investigated the efficacy and tolerability of low energy
      shocks for termination of atrial fibrillation in patients, using an endocardial
      electrode configuration that embraced both atria. BACKGROUND: In animals, low
      energy biphasic shocks delivered between electrodes in the coronary sinus and
      right atrium have effectively terminated atrial fibrillation. If human
      defibrillation thresholds are sufficiently low, atrial defibrillation could be
      achieved in conscious patients using an implanted device. METHODS: Twenty-two
      consecutive patients with stable atrial fibrillation were studied during
      electrophysiologic testing. Biphasic R wave synchronous shocks were delivered
      between large surface area electrodes in the coronary sinus and high right
      atrium, using a step-up voltage protocol starting at 10 or 20 V and increasing to
      a maximum of 400 V. Patients were conscious at the start of the study and were
      asked to report on symptoms but were sedated later if shocks were not tolerated.
      RESULTS: Cardioversion was achieved in all 19 patients who completed the study,
      with a mean (+/- SD) leading-edge voltage of 237 +/- 55 V (range 140 to 340) and
      mean energy of 2.16 +/- 1.02 J (range 0.7 to 4.4). The mean maximal shock
      delivered without sedation was 116 +/- 51 V (range 60 to 180). No proarrhythmia
      or mechanical complications occurred. CONCLUSIONS: The delivery of biphasic R
      wave synchronous shocks between the high right atrium and coronary sinus can
      terminate atrial fibrillation with very low energies. General anaesthesia is not
      required, and a minority of fully conscious patients are able to tolerate this
      method of cardioversion.

PMID- 7722133
TI  - Transesophageal echocardiographically facilitated early cardioversion from atrial
      fibrillation using short-term anticoagulation: final results of a prospective 4.5
      year study.
AB  - OBJECTIVES: We sought to validate the safety of transesophageal
      echocardiographically guided early cardioversion in conjunction with short-term
      anticoagulation as a strategy for guiding early cardioversion in hospitalized
      patients with atrial fibrillation. BACKGROUND: Because atrial thrombi are poorly
      seen by conventional imaging techniques, several weeks of prophylactic
      anticoagulation is routinely prescribed before cardioversion. Transesophageal
      echocardiography is a superior test for identifying atrial thrombi; preliminary
      feasibility studies have supported its use to guide early cardioversion for
      patients in whom no thrombus is observed, but safety has not been validated in
      any large series. METHODS: All patients admitted to hospital with atrial
      fibrillation during a 4.5-year period were screened. The inclusion criterion was
      a clinical duration of atrial fibrillation > 2 days or of unknown duration.
      Patients received anticoagulation with heparin/warfarin and underwent
      conventional transthoracic echocardiography followed by transesophageal study.
      Patients in whom transesophageal echocardiography revealed no atrial thrombus
      underwent pharmacologic or electrical cardioversion followed by warfarin therapy
      for 1 month. Cardioversion was deferred in patients with evidence of atrial
      thrombi, and they received prolonged warfarin treatment. RESULTS: Two hundred
      thirty-three patients (86% of those eligible) agreed to participate, and 230
      underwent transesophageal echocardiography. Transesophageal echocardiography
      identified 40 atrial thrombi (left atrium 34, right atrium 6) in 34 patients
      (15%). One hundred eighty-six (95%) of 196 patients without thrombi had
      successful cardioversion to sinus rhythm, all without prolonged anticoagulation,
      and none (0%, 95% confidence interval 0% to 1.6%) experienced a clinical
      thromboembolic event. Eighteen patients with atrial thrombi underwent uneventful
      cardioversion after prolonged anticoagulation. CONCLUSIONS: Compared with smaller
      series that have shown only feasibility, this large prospective and consecutive
      study of patients undergoing transesophageal echocardiographically facilitated
      early cardioversion in conjunction with short-term anticoagulation validates the
      safety of this strategy. This treatment algorithm has a safety profile similar to
      conventional therapy and minimizes both the period of anticoagulation and the
      overall duration of atrial fibrillation.

PMID- 7722134
TI  - Transesophageal echocardiographic screening for atrial thrombus before
      cardioversion of atrial fibrillation: when should we look before we leap?

PMID- 7722135
TI  - Radiofrequency catheter ablation of common atrial flutter in 80 patients.
AB  - OBJECTIVES: The purpose of this study was to evaluate the efficacy and safety of
      radiofrequency catheter ablation of common atrial flutter and to determine the
      optimal target sites in a large series of patients. BACKGROUND: Recent studies
      report the efficacy of radiofrequency current application in the low right atrial
      region to interrupt and prevent recurrences of common atrial flutter. However,
      larger groups of patients are required to confirm the efficacy of this technique
      and to specify the target sites. METHODS: Two different approaches were used to
      target the ablation site in 80 consecutive patients. In the first 50 patients,
      target sites were localized using both anatomic landmarks and electrophysiologic
      variables. Three anatomic landmarks were used: area 1 = between the tricuspid
      valve and inferior vena cava orifice; area 2 = between the tricuspid valve and
      coronary sinus ostium; area 3 = between the inferior vena cava and coronary
      sinus. The electrophysiologic criterion was to ablate when there was a stable
      atrial electrogram during the plateau phase. In the next 30 patients we assessed
      the effect of application of radiofrequency energy in a single line in area 1, 2
      or 3 in groups of 10 patients. RESULTS: Overall atrial flutter was interrupted
      and rendered noninducible after a single session in 72 patients (90%) and could
      not be interrupted in 8 (10%). The mean (+/- SD) number of radiofrequency
      applications was 12 +/- 8. After a mean (+/- SD) follow-up of 20 +/- 8 months,
      recurrences occurred in 14 patients (17%). The location of the final successful
      site in the first group of 50 patients was in area 1 in 39%, area 2 in 36% and
      area 3 in 25%. In the next 30 patients, when lines of radiofrequency lesions were
      placed at several sites, they produced success rates of 70%, 40% and 10% at areas
      1, 2 and 3, respectively. CONCLUSIONS: Radiofrequency catheter ablation of atrial
      flutter can be performed with a high success rate and is safe. The highest
      success rate is achieved with radiofrequency energy applied in the isthmus
      between the inferior vena cava orifice and tricuspid valve.

PMID- 7722136
TI  - Comparison of defibrillation probability of success curves for an endocardial
      lead configuration with and without an inactive epicardial patch.
AB  - OBJECTIVES: This study sought to assess the effect of passive "bystander"
      epicardial electrodes on defibrillation efficacy. BACKGROUND: We hypothesized
      that an inactive epicardial patch placed in an area of low potential gradient
      from an endocardial electrode shock might affect defibrillation efficacy through
      its effects on the shock field and the underlying potential gradient. METHODS: We
      studied the effects of an inactive 18-cm2 titanium mesh patch placed on the
      anterolateral left ventricular epicardium on the 50% probability of successful
      defibrillation. A biphasic shock with both phases 6 ms in duration was delivered
      between superior vena cava and right ventricular catheter electrodes 10 s after
      the electrical induction of ventricular fibrillation. Six dogs underwent an
      up/down defibrillation protocol randomized with or without the patch on the
      heart. RESULTS: Mean 50% (+/-) probability point for energy doubled with the
      conductive patch on the heart, from 8.0 +/- 3.2 to 16.8 +/- 7.0 J (p < 0.01), and
      leading-edge voltage increased from 334 +/- 64 to 477 +/- 98 V (p < 0.01). Mean
      50% probability points for energy and leading-edge voltage were not significantly
      changed when the procedure was repeated using a nonconductive patch in another
      six dogs as a control group. In a saline-saturated foam model, measurements from
      electrodes placed around and under the patch revealed a 72% mean decrease in the
      potential gradient in the foam under the conductive patch. CONCLUSIONS: A passive
      defibrillator patch can markedly increase the energy requirements for
      defibrillation, probably by decreasing the potential gradient under the patch.
      These results suggest the use of caution when passive electrodes are present, for
      example, when a patient receives a nonthoracotomy defibrillator system while
      epicardial electrodes from a previously implanted system are left in place.

PMID- 7722137
TI  - Directional atherectomy versus balloon angioplasty for coronary ostial and
      nonostial left anterior descending coronary artery lesions: results from a
      randomized multicenter trial. The CAVEAT-I investigators. Coronary Angioplasty
      Versus Excisional Atherectomy Trial.
AB  - OBJECTIVES: We hypothesized that atherectomy would be superior to balloon
      angioplasty for ostial and nonostial left anterior descending coronary artery
      lesions. BACKGROUND: Balloon angioplasty of ostial coronary artery lesions has
      been associated with a lower procedural success rate and a higher rate of
      complications and of restenosis than angioplasty of nonostial stenoses.
      Directional coronary atherectomy has been proposed as an alternative therapy for
      ostial lesions. METHODS: In the Coronary Angioplasty Versus Excisional
      Atherectomy Trial (CAVEAT-I), 1,012 patients were randomized to undergo either
      procedure; 563 patients had proximal left anterior descending coronary artery
      lesions, of which 74 were ostial. We compared balloon angioplasty with
      directional atherectomy for early and 6-month results for ostial as well as
      nonostial proximal left anterior descending coronary artery lesions. RESULTS:
      Directional atherectomy led to an initially higher gain in minimal lumen diameter
      for ostial lesions (1.13 vs. 0.56 mm, respectively, p < 0.001) but a higher rate
      of adjudicated non-Q wave myocardial infarction (24% vs. 13%, respectively, p <
      0.001) than balloon angioplasty and no improvement in restenosis rates (48% vs.
      46%, respectively). In the nonostial proximal left anterior descending coronary
      artery lesions, angiographic restenosis was reduced (51% vs. 66%, p = 0.012), but
      this was also associated with a higher rate of periprocedural myocardial
      infarction (8% vs. 2%, p = 0.008 by site and 24% vs. 8%, p < 0.001 by
      adjudication) and no difference in the need for subsequent coronary artery bypass
      surgery (7.3% vs. 8.4%, respectively) or repeat percutaneous coronary
      intervention (24% vs. 26%, respectively). CONCLUSIONS: For ostial left anterior
      descending coronary artery stenoses, both procedures yielded similar rates of
      initial success and restenosis, but atherectomy was associated with more non-Q
      wave myocardial infarction. In this trial the predominant angiographic benefit
      (increased early gain and less angiographic restenosis) of atherectomy for the
      left anterior descending coronary artery was in proximal nonostial lesions.
      However, the tradeoffs for this angiographic advantage were more in-hospital
      myocardial infarctions and no decrease in clinical restenosis.

PMID- 7722138
TI  - Coronary blood flow reserve in acute aortic regurgitation.
AB  - OBJECTIVES: This study sought to determine the impact of acute aortic
      regurgitation on coronary blood flow reserve and phasic epicardial coronary blood
      flow in closed-chest dogs. BACKGROUND: Hemodynamic changes in acute aortic
      regurgitation are known to precipitate myocardial ischemia. Coronary blood flow
      reserve has not been studied in closed-chest experimental preparations with acute
      aortic regurgitation. METHODS: Graded temporary acute aortic regurgitation was
      produced in 11 mongrel dogs. Phasic coronary blood flow velocities were measured
      using a Doppler guide wire. Coronary flow reserve was defined as the ratio of the
      time average of spectral peak velocity after administration of papaverine to that
      of the baseline state. RESULTS: Under control conditions (mean [+/- SEM]
      diastolic blood pressure 82.2 +/- 4.5 mm Hg), coronary flow reserve was 3.51 +/-
      0.27 with predominantly diastolic epicardial coronary blood flow. With mild acute
      aortic regurgitation (diastolic blood pressure 61.8 +/- 3.0 mm Hg), coronary flow
      reserve decreased to 2.38 +/- 0.27, with an increase in phasic systolic
      epicardial coronary blood flow. At the onset of moderate acute aortic
      regurgitation (diastolic blood pressure 42.1 +/- 0.9 mm Hg), coronary flow
      reserve declined further to 1.46 +/- 0.12, and the phasic systolic epicardial
      coronary blood flow became more prominent. With severe aortic regurgitation
      (diastolic blood pressure 29.2 +/- 2.2 mm Hg), coronary flow reserve reached 1.20
      +/- 0.05, and the phasic epicardial coronary blood flow pattern was found to be
      predominantly systolic with retrograde diastolic flow. The ratio of diastolic to
      systolic pressure-time indexes with severe aortic regurgitation suggested
      subendocardial underperfusion. CONCLUSIONS: This study demonstrates a marked
      decline in coronary blood flow reserve and documents a progressive change in the
      phasic epicardial blood flow to a predominantly systolic pattern with increasing
      degrees of acute aortic regurgitation.

PMID- 7722139
TI  - Frequency and explanation of false negative diagnosis of aortic dissection by
      aortography and transesophageal echocardiography.
AB  - OBJECTIVES: This study was designed to define the frequency and explanation of
      false negative diagnosis of aortic dissection by aortography and transesophageal
      echocardiography. BACKGROUND: Aortography and transesophageal echocardiography
      have been widely utilized to diagnose aortic dissection. Previous reports have
      not fully addressed the reasons why these studies yield false negative results in
      a large number of patients with aortic dissection. METHODS: Sixty-five
      consecutive patients with aortic dissection underwent aortography and
      transesophageal echocardiography. Diagnosis of aortic dissection was confirmed at
      operation or by computed tomography in all patients. RESULTS: Biplane
      transesophageal echocardiograms yielded false negative results in two patients
      (sensitivity 97% [63 of 65]). Both patients had well localized DeBakey type II
      aortic dissection. The diagnosis was probably missed because of image
      interference from the air-filled trachea and mainstem bronchi. In both patients,
      the dissection was readily identified by aortography. Aortograms yielded false
      negative results in 15 patients (sensitivity 77% [50 of 65]); the aortic
      dissection was type I in 7 patients, type II in 1 and type III in 7. The
      dissection in all 15 patients was readily identified by transesophageal
      echocardiography. The missed diagnosis was probably due to a completely
      thrombosed false lumen or intramural hematoma with noncommunicating dissection in
      13 patients and to a large ascending aortic aneurysm with nearly equal flow on
      both sides of the intimal flap in 2. In no patient was the diagnosis missed by
      both aortography and transesophageal echocardiography. CONCLUSION:
      Transesophageal echocardiography is an excellent screening tool for aortic
      dissection. However, it may miss small type II aortic dissections localized to
      the upper portion of the ascending aorta because of image interference from the
      air-filled trachea. An intramural hematoma cannot be easily visualized by
      aortography, and this lesion is the principal reason for false negative
      aortographic findings.

PMID- 7722140
TI  - Endothelium-derived relaxing factor is important in mediating the high output
      state in chronic severe anemia.
AB  - OBJECTIVES: We evaluated the endothelial and vascular smooth muscle function in
      patients with chronic severe anemia to determine whether increased basal nitric
      oxide levels contribute to the systemic vasodilation and high cardiac output seen
      in these patients. BACKGROUND: Patients with chronic severe anemia have a high
      output state due to a low systemic vascular resistance. However, the cause of the
      low vascular resistance is unclear. Because hemoglobin is a potent inhibitor of
      endothelium-derived relaxing factor, we postulated that in chronic severe anemia,
      low circulating hemoglobin results in reduced inhibition of endothelium-derived
      relaxing factor. The basal endothelium-derived relaxing factor activity therefore
      increases, and this contributes significantly to the low systemic vascular
      resistance and the hyperdynamic state seen in this condition. METHODS:
      Hemodynamic variables and forearm blood flow (using plethysmography) were
      measured in eight patients with chronic severe anemia before (hematocrit 16 +/-
      2% [mean +/- SD]) and within 24 h of red blood cell transfusion (n = 6,
      hematocrit 30 +/- 1%) and in six control subjects. The effect on baseline blood
      flow of blocking endothelium-derived relaxing factor activity with NG-monomethyl
      L-arginine was investigated. In addition, the effects of both endothelium
      dependent and endothelium-independent vasodilators on forearm blood flow were
      tested. RESULTS: Baseline forearm blood flow was markedly increased in untreated
      patients (6.5 +/- 1.2 ml/min per 100 ml) compared with that in control subjects
      (2.8 +/- 0.7 ml/min per 100 ml, p < 0.0001, 95% confidence interval [CI] for
      difference -5 to -2.5). Red blood cell transfusion significantly reduced blood
      flow in the anemic patients to 3.5 +/- 1.1 ml/min per 100 ml (p < 0.001, 95% CI
      for difference -4.9 to -1.9), which was not significantly different from that in
      control subjects; increased systemic vascular resistance (796 +/- 141 to 1,230 +/
      151 dynes.s.cm-5, p < 0.001); and decreased cardiac output (4.9 +/- 0.6 to 3.5
      +/- 0.5 liters/min per m2, p < 0.001). NG-monomethyl-L-arginine (16 mumol/min), a
      specific inhibitor of endothelium-derived relaxing factor, reduced forearm blood
      flow by an equal amount (p = 0.9, 95% CI for difference -0.7 to 0.8) in control
      subjects (0.98 +/- 0.39 ml/min) and treated patients (1.03 +/- 0.8 ml/min) but
      caused a threefold greater decrease in flow (2.9 +/- 0.9 ml/min) in untreated
      patients (p = 0.0003, 95% CI for difference between untreated patients and
      control subjects 1.1 to 2.7). These findings suggest increased basal endothelium
      derived relaxing factor activity in patients with anemia. Stimulated forearm
      blood flows (both endothelium dependent and endothelium independent) were similar
      in all groups, confirming normal endothelial and smooth-muscle function.
      CONCLUSIONS: These findings support the hypothesis that enhanced basal
      endothelium-derived relaxing factor activity makes an important contribution to
      the low systemic vascular resistance in chronic severe anemia.

PMID- 7722141
TI  - Increased echodensity of myocardial wall in the diabetic heart: an ultrasound
      tissue characterization study.
AB  - OBJECTIVES: We sought to characterize myocardial echodensity in asymptomatic
      patients with insulin-dependent diabetes and normal conventional two-dimensional
      echocardiographic findings to determine whether ultrasound tissue
      characterization can detect ultrastructural changes in myocardium, such as an
      increase in collagen content. BACKGROUND: Fibrosis alters the acoustic properties
      of the heart in animals and humans, and these changes are detectable by cardiac
      tissue characterization with ultrasound. Early changes detected in the diabetic
      heart include increased interstitial collagen deposition. METHODS: Using two
      dimensional echocardiography, we evaluated 26 asymptomatic patients with insulin
      dependent diabetes with normal regional and global rest function, and 17 age- and
      gender-matched control subjects. By selection, all diabetic patients were
      normotensive and had negative maximal exercise stress test results to avoid the
      confounding effects of hypertension and coronary artery disease. Using an
      echocardiographic instrument implemented at the Institute of Clinical Physiology,
      we performed an on-line radiofrequency analysis to obtain quantitative operator
      independent measurements of the integrated back-scatter signal of the ventricular
      septum and posterior wall. The integrated values of the radiofrequency signal
      from the myocardial wall were normalized for those from the pericardial interface
      and were expressed as percentages (integrated backscatter index). RESULTS:
      Diabetic patients showed a significant increase in myocardial echodensity both in
      the septum ([mean +/- SD] 36.6 +/- 8.1 vs. 23.6 +/- 4.4, p < 0.0001) and
      posterior wall (21.2 +/- 5.3 vs. 18.4 +/- 3.7, p < 0.001). By individual patient
      analysis, 17 patients exceeded the 95% confidence limits for normal myocardial
      echocardiographic reflectivity found in normal subjects, and only 3 had a
      relatively abnormal transmitral Doppler filling pattern (E/A ratio), mainly
      consisting of an abnormally increased late peak flow velocity (65% vs. 11%, p <
      0.001). The increased myocardial intensity was similar in patients with (n = 16)
      and without (n = 10) noncardiac complications, such as retinopathy or nephropathy
      (37.5 +/- 7.9% vs. 35.0 +/- 8.3%, p = 0.35). CONCLUSIONS: Abnormally increased
      myocardial echodensity, possibly related to collagen deposition, can be detected
      in asymptomatic diabetic patients with normal rest function. Theoretically, this
      finding might be considered a very early preclinical alteration potentially
      related to subsequent development of diabetic cardiomyopathy.

PMID- 7722142
TI  - Intraaortic spring coil loops: early and late results.
AB  - OBJECTIVES: Our aim was to determine the late fate of intraaortic spring coil
      loops after embolization of aortopulmonary vessels. BACKGROUND: In some
      aortopulmonary collateral vessels and patent ductus arteriosi, the narrowest
      segment is close to the aorta; coils used to close such vessels will "straddle"
      the lesion, allowing one or more coil loops to protrude into the aortic lumen.
      The consequences of this procedure are unknown. METHODS: We reviewed the
      cineangiograms of all patients who had at least one aortopulmonary collateral
      vessel or patent ductus arteriosus closure between January 1, 1988 and August 31,
      1993. From this group, 53 patients had multiple-plane angiographic evidence of
      intraaortic coil loops. All subsequent cineangiograms were reviewed to determine
      coil position or movement and evidence of recanalization or endothelial coverage
      of the coil loop. We also reviewed each hospital record or communicated directly
      with referring physicians to identify any subsequent complications such as emboli
      or endocarditis. RESULTS: Of the 53 patients with intraaortic coil loops, 49
      patients had closure of one or more aortopulmonary collateral vessels (59
      vessels), and 4 had closure of a patient ductus arteriosus (4 vessels). Patient
      follow-up ranged from 1 day to 66 months (median 20 months); follow-up was not
      available in 6 patients. Five of the 53 patients (9.3%; 95% confidence limits
      [CL] 3.1% to 20.7%) died at operation or of end-stage heart failure. Patients
      with late angiography had no residual flow in 31 of 35 aortopulmonary collateral
      vessels (88.6%; 95% CL 73.3% to 96.8%), and 0.5 mm separated the coil and aortic
      contrast column in all 12 coils with adequate angiography, suggesting endothelial
      coverage of the intraaortic coil loop. No episodes of stroke, embolic events,
      endocarditis or coil migration were reported. CONCLUSIONS: Although coil
      occlusion of aortopulmonary collateral vessels or patent ductus arteriosi may
      produce intraaortic coil loops, endothelialization appears routine. No late
      complications associated with intraaortic coil loops were observed.

PMID- 7722143
TI  - Exercise capacity and incidence of myocardial perfusion defects after Kawasaki
      disease in children and adolescents.
AB  - OBJECTIVES: This study evaluated exercise performance and myocardial perfusion
      during exercise in patients with Kawasaki disease who had a broad spectrum of
      residual coronary abnormalities. BACKGROUND: Reports of exercise performance
      after Kawasaki disease have generally included a small number of patients
      evaluated by various protocols, frequently with incomplete data. Myocardial
      perfusion studies have usually been limited to those using pharmacologically
      induced coronary vasodilation. Therefore, to our knowledge there has not been a
      large study directly correlating exercise performance, electrocardiographic (ECG)
      changes and myocardial perfusion imaging. METHODS: Forty-six patients were
      classified into three groups on the basis of coronary artery status: group 1 (n =
      27) had no objective evidence of coronary artery lesions; group 2 (n = 11) had
      resolved aneurysms; group 3 (n = 8) had persistent coronary aneurysms. All
      patients underwent exercise testing with monitoring of ECG changes and oxygen
      consumption. Single-photon emission computed tomographic imaging was performed at
      rest and during peak exercise using technetium-99m sestamibi. RESULTS: Maximal
      oxygen consumption was within normal limits and was similar for all three groups.
      Five patients had mild ST segment changes at peak exercise. Two of these patients
      had stress-induced perfusion defects. Myocardial perfusion defects were present
      in 37% of patients in group 1, 63% in group 2 and 100% in group 3. Perfusion
      defects corresponded to the coronary artery lesion site in all but three
      patients. CONCLUSIONS: Maximal oxygen consumption is normal after Kawasaki
      disease regardless of coronary artery status. Stress-induced perfusion defects
      are frequent even in the absence of coronary abnormalities and are common in the
      absence of ST segment changes suggestive of ischemia.

PMID- 7722144
TI  - Kawasaki disease: unsafe at any age?

PMID- 7722145
TI  - Interaction between afterload and contractility in the newborn heart: evidence of
      homeometric autoregulation in the intact circulation.
AB  - OBJECTIVES: We undertook the present study to determine whether afterload and
      contractility interact in the hearts of newborn lambs. We specifically
      investigated whether stepwise increases in afterload increase contractility.
      BACKGROUND: Several studies in the isolated and intact adult dog heart have shown
      that afterload and contractility are not independent determinants of cardiac
      performance; rather, they interact. Afterload and contractility are unlikely to
      interact in the newborn heart because the factors that may mediate the
      interaction in the adult are missing in the newborn. METHODS: We measured
      contractility at different steady state levels of afterload in seven newborn
      lambs under complete anesthesia. Contractility was measured by three different
      indexes: end-systolic pressure-volume relations (slope and volume position);
      preload-corrected first derivative of left ventricular pressure (dP/dtmax); and
      preload-corrected stroke work. Left ventricular pressure and volume were measured
      with a micromanometer and conductance catheter, respectively. Preload and
      afterload were manipulated by inflating or deflating a balloon catheter in the
      inferior vena cava and descending thoracic aorta, respectively. Data are
      expressed as mean value +/- 1 SD. RESULTS: Stepwise increases in afterload
      increased contractility, independent of which of the three indexes was used. The
      slope of the end-systolic pressure-volume relation increased from a mean baseline
      value of 4.44 +/- 2.43 to 6.69 +/- 2.89 kPa/ml at the highest level of afterload.
      Concomitantly, volume at 14 kPa of the end-systolic pressure-volume relation
      decreased from 3.34 +/- 1.52 ml at baseline to 1.12 +/- 0.83 ml at the highest
      afterload. The other two indexes showed qualitatively similar changes. Beats
      selected from unloading interventions on the basis of the same end-diastolic
      volume for each level of afterload showed no difference in stroke volume.
      CONCLUSIONS: This study in newborn lambs demonstrates that stepwise increases in
      afterload increase contractility considerably and that this enables the heart to
      maintain stroke volume at different levels of afterload. This forms direct
      evidence for the existence of homeometric autoregulation in the intact newborn
      heart.

PMID- 7722146
TI  - Echocardiographic Fourier phase and amplitude imaging for quantification of
      ischemic regional wall asynergy: an experimental study using coronary
      microembolization in dogs.
AB  - OBJECTIVES: This study investigated whether echocardiographic Fourier phase and
      amplitude imaging can be used to evaluate ischemia-related regional wall
      asynergy. BACKGROUND: Because myocardial ischemia delays the onset and peak of
      endocardial inward motion and reduces its magnitude, Fourier phase and amplitude
      analysis of two-dimensional echocardiograms may be used to evaluate regional wall
      motion abnormalities objectively by analyzing temporal sequence and magnitude of
      endocardial motion. METHODS: Digital cine loops of left ventricular long- and
      short-axis views were obtained in six anesthetized dogs at baseline and 1 to 30
      min after coronary microembolization and were mathematically transformed using a
      first-harmonic Fourier algorithm to obtain phase angles and amplitudes of
      endocardial segments. Mean phase angles and amplitudes were compared with visual
      wall motion analysis based on a scoring system and quantitative analysis based on
      segmental fractional area shortening derived from planimetry. RESULTS:
      Microembolization delayed segmental phase angles by 47 +/- 44 degrees in mild to
      moderate hypokinesia (fractional shortening [mean +/- SD] 41 +/- 13%) and by 77
      +/- 63 degrees in severe hypokinesia (fractional shortening 13 +/- 5%) and
      reduced segmental amplitudes from 80 +/- 36 gray level intensity at baseline to
      53 +/- 34 in segments developing mild to moderate hypokinesia, and from 93 +/- 36
      to 35 +/- 28 gray level intensity in segments developing severe hypokinesia.
      Shifts in segmental phase angles correlated better with dynamic shifts in
      segmental fractional area shortening than did changes in wall motion score (r = 
      0.65 vs. r = 0.52, p < 0.001). CONCLUSIONS: Echocardiographic Fourier phase
      imaging can be used to evaluate ischemia-related regional wall asynergy,
      displaying contraction sequence and magnitude in a simple, objective format.

PMID- 7722147
TI  - Effect of low dose aspirin on cardiorenal function and acute hemodynamic response
      to enalaprilat in a canine model of severe heart failure.
AB  - OBJECTIVES: This study examined the effect of low dose aspirin on cardiorenal and
      neurohumoral function and on the acute hemodynamic response to enalaprilat in a
      canine model of heart failure. BACKGROUND: Low dose aspirin is frequently
      prescribed for patients with systolic dysfunction who also benefit from
      angiotensin-converting enzyme inhibition. Although high doses of potent cyclo
      oxygenase inhibitors cause fluid retention and vaso-constriction and antagonize
      the effects of angiotensin-converting enzyme inhibitors, the effects of low dose
      aspirin in heart failure are unknown. METHODS: A model of heart failure was
      produced in 11 mongrel dogs by rapid ventricular pacing (250 beats/min for 12 to
      14 days). Five dogs received 325 mg aspirin/day for the final 4 days of pacing
      before the acute experiment; six control dogs received no aspirin. Cardiorenal
      and neurohumoral function was measured during chloralose anesthesia. Hemodynamic
      and renal responses to enalaprilat were assessed. RESULTS: Both groups
      demonstrated severe heart failure with decreased cardiac output; increased atrial
      pressures and systemic resistance; activation of plasma renin activity,
      aldosterone and atrial natriuretic factor; and sodium retention. Low dose aspirin
      had no detrimental effect on cardiorenal or neurohumoral function. Mean arterial
      pressure, pulmonary capillary wedge pressure and systemic vascular resistance
      decreased to a similar degree with enalaprilat in both groups. There was no
      difference between the groups with respect to renal response to enalaprilat.
      CONCLUSIONS: The present study demonstrates that low dose aspirin has no adverse
      effect on hemodynamic, neurohumoral or renal function in heart failure.
      Furthermore, aspirin has no adverse effect on the acute response to enalaprilat.
      These findings suggest that there is no contraindication to concomitant treatment
      with low dose aspirin and angiotensin-converting enzyme inhibitors in humans with
      heart failure.

PMID- 7722148
TI  - Intracoronary irradiation markedly reduces neointimal proliferation after balloon
      angioplasty in swine: persistent benefit at 6-month follow-up.
AB  - OBJECTIVES: This study examined the long-term efficacy of intracoronary
      irradiation for limiting neointimal proliferation after overstretch balloon
      angioplasty in a porcine model of restenosis. In addition, this study sought to
      identify any adverse late sequelae of this novel therapy for restenosis.
      BACKGROUND: Restenosis after coronary angioplasty represents in part a
      proliferative response of vascular smooth muscle at the site of injury. We have
      shown previously that high dose intracoronary radiation induces focal medial
      fibrosis and markedly reduces neointimal proliferation early after balloon
      angioplasty in swine. METHODS: Twenty-two juvenile swine underwent intervention
      at a target segment of the left coronary artery. In 11 swine, a 2-cm ribbon of
      iridium-192 was positioned at the target segment and 2,000 cGy was delivered to
      the vessel wall. Subsequently, overdilation balloon angioplasty was performed at
      the irradiated segment. In 11 control swine, overdilation balloon angioplasty was
      performed without previous irradiation. Twenty animals survived and underwent
      histopathologic analysis at 180 +/- 8 days. RESULTS: Mean (+/- SD) neointimal
      area was 1.59 +/- 0.78 and 0.46 +/- 0.35 mm2 (p < 0.001) in control and
      irradiated animals, respectively. Mean percent area stenosis was 37.9 +/- 12.4%
      and 14.2 +/- 9.0% (p < 0.001) in the control and irradiated animals,
      respectively. Thus, by 6-month follow-up, intracoronary irradiation before
      balloon angioplasty had reduced the bulk of the neointimal lesion by 71.1% and
      reduced percent area stenosis by 62.5% compared with that in control animals.
      There was no evidence of radiation vasculopathy or myocardial damage at 6 months.
      CONCLUSIONS: Intracoronary irradiation (2,000 cGy) produces persistent impairment
      of neointimal proliferation 6 months after balloon injury, with no evidence of
      late radiation sequelae.

PMID- 7722149
TI  - Effects of heating on impulse propagation in superfused canine myocardium.
AB  - OBJECTIVES: The goal of the study was to quantify the response of myocardial
      impulse propagation to hyperthermia and identify the temperatures required for
      transient and permanent block in conduction. BACKGROUND: Although it is generally
      accepted that the effects of radiofrequency ablation are thermally mediated, the
      precise response of myocardial impulse conduction to heating remains to be
      quantified. METHODS: Twenty-three preparations of ventricular myocardium from 10
      beagle dogs were superfused at 36.5 to 37.5 degrees C and paced at a cycle length
      of 600 ms. Heating was performed for 30 s at 5-min intervals by an independent
      flow of heated superfusate. A 16-electrode grid was used to record extracellular
      electrograms directly before each heating episode (control value) and at 10, 20
      and 30 s. RESULTS: Between 38.5 and 45.4 degrees C, conduction velocity was
      higher than that at the directly preceding control value (p < 0.05), reaching a
      maximum of 114% between 41.5 and 42.5 degrees C. Above 45.4 degrees C, a gradual
      decrease occurred, with transient block (absence of impulse conduction for < or =
      5 min) after heating to 49.5 to 51.5 degrees C. This was followed by tachycardia
      in 69% of all cases immediately after cessation of heating. Permanent block
      occurred after a significantly higher temperature of 51.7 to 54.4 degrees C had
      been reached. Pacing at sites allowing preferential conduction either parallel or
      perpendicular to fiber orientation caused no difference in reaction to heating.
      Repeated heating of some preparations to 47.0 to 50.5 degrees C revealed no
      cumulative effects on conduction velocity. CONCLUSIONS: Transient and permanent
      block in impulse conduction occurred at 49.5 to 51.5 degrees C and 51.7 to 54.4
      degrees C, respectively, in superfused canine myocardium, the former frequently
      being followed directly by tachycardia. Reaction of conduction velocity to
      hyperthermia was independent of myocardial fiber orientation and number of
      preceding heating episodes. Results may contribute to a better understanding of
      electrophysiologic phenomena observed during radiofrequency ablation procedures.

PMID- 7722151
TI  - Peer review or poor review?

PMID- 7722150
TI  - Clinical competence in electrocardiography. A statement for physicians from the
      ACP/ACC/AHA Task Force on clinical privileges in cardiology.

PMID- 7722152
TI  - Assessment of cardiovascular autonomic function.

PMID- 7722153
TI  - Integrated Doppler backscatter power.

PMID- 7722154
TI  - Use of backscattered Doppler signal intensity in estimation of volume flow
      ratios.

PMID- 7722155
TI  - Pathogenesis of stroke after nonanterior myocardial infarction.

PMID- 7722156
TI  - The standard exercise test is still the most cost-effective.

PMID- 7722157
TI  - Health care reform. AAAI Board of Directors.

PMID- 7722158
TI  - House dust mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus)
      prevalence in the rooms and hallways of a tertiary care hospital.
AB  - BACKGROUND: House dust mites, Dermatophagoides farinae and Dermatophagoides
      pteronyssinus, are important components in the development of asthma. OBJECTIVE:
      We measured the prevalence of house dust mites in a tertiary care hospital
      located in a temperate geographic region where dust mites were prevalent in
      homes. METHODS: The density of Dermatophagoides spp. was measured in hospital
      hallways, carpeted patients' rooms, and noncarpeted patients' rooms by vacuuming
      the floor in the summer and winter seasons. Bedrooms in the homes of employees
      were sampled as a summer control group. A total of 141 dust samples was obtained.
      RESULTS: No D. farinae or D. pteronyssinus was found in 60 hospital dust samples
      that were obtained during the winter season. Although mites were found in some
      locations in the hospital during the summer dust collection, mite density in
      these locations and the average mite density for all samples were insignificant.
      During the summer dust samples from the bedroom carpets of all employees' homes
      sampled were positive for mites, with many homes having moderate or high
      populations (range, 22 to 8340 mites per gram of dust). CONCLUSIONS: The dust
      mite prevalence in a hospital could be kept very low even though mite levels in
      employees' homes were moderate to high. The factors responsible for the low mite
      density in the hospital were maintenance of low relative humidity, use of low
      pile carpets, and good housekeeping and laundering practices.

PMID- 7722159
TI  - Effect of prolonged use of inhaled steroids on the cellular immunity of children
      with asthma.
AB  - BACKGROUND: Systemic corticosteroids may affect the cellular immunity, but there
      is no available controlled data on such effects associated with a prolonged use
      of inhaled corticosteroids. OBJECTIVE: The investigation was designed to study
      the effect of long-term inhaled beclomethasone dipropionate in daily doses of up
      to 600 micrograms on cellular immune functions. METHODS: Twenty-four children
      with asthma treated with inhaled beclomethasone dipropionate for a mean of 22.6
      months were compared with 16 children with asthma not treated with an inhaled
      steroid and with 20 healthy adults. Cellular immune parameters included
      differential white blood count, T- and B-cell numbers, T helper and suppressor
      counts, T-cell mitogenic transformation, and interleukin-1 and interleukin-2
      secretion. RESULTS: There was no difference in any of the studied cellular immune
      functions among the three study groups. CONCLUSION: Long-term use of inhaled
      beclomethasone dipropionate by children with asthma, at daily doses of up to 600
      micrograms, has no effect on certain parameters of cellular immunity.

PMID- 7722160
TI  - Gender risk for anaphylactoid reaction to radiographic contrast media.
AB  - BACKGROUND: Female predominance has been reported previously in series of
      anaphylaxis cases; however, no definite precedent has been established for
      greater risk of anaphylactoid reaction caused by contrast media infusion on the
      basis of gender. OBJECTIVE: This study was designed to determine whether greater
      risk for anaphylactoid reaction caused by intravenous contrast media infusion
      exists in association with female gender. METHODS: Rates of anaphylactoid and
      severe anaphylactoid reaction, according to gender, were determined in a sample
      of 5264 consecutive patients receiving conventional radiocontrast media during
      performance of computed tomography. RESULTS: Of 80 adverse reactions caused by
      contrast media infusion, 73 (1.39%) were classified as anaphylactoid in nature.
      Among 5191 patients who received intravenous contrast media without experiencing
      an anaphylactoid reaction, there were 2642 male patients (51%) and 2549 female
      patients (49%); reactors included 22 male patients and 51 female patients (odds
      ratio = 2.40, 95% confidence interval = 1.42-4.10, p < 0.0005). Female patients
      also comprised 21 of 22 cases of severe anaphylactoid reaction (odds ratio =
      21.77, 95% confidence interval = 3.13-435.12, p < 0.0005). CONCLUSION: Greater
      risk for anaphylactoid and severe anaphylactoid reaction exists in association
      with female gender. Further studies are needed to identify mechanisms that can
      explain this risk. The importance of these findings for cost-effective use of
      lower osmolality contrast media need to be determined.

PMID- 7722161
TI  - Physician-targeted program on inhaled therapy for childhood asthma.
AB  - BACKGROUND: Inhaled medications are the mainstay of asthma therapy, but
      significant deficiencies exist in the knowledge and skills of physicians
      regarding use of metered-dose inhalers (MDI) and spacer devices. OBJECTIVE: We
      developed, implemented, and evaluated the effects of a physician-targeted
      educational program on inhaled therapy in a group of pediatric residents in our
      institution. METHODS: Patient-directed instruction sheets on aerosol therapy were
      developed on the basis of literature review and expert guidelines. These served
      to establish a consistent foundation for the educational curriculum. The program
      was delivered through one-on-two teaching sessions (45 minutes). Residents were
      provided with a summary of theoretical and practical information and with devices
      for practice (a placebo MDI, InspirEase and AeroChamber holding chambers, and the
      AeroChamber device with mask). Each session included review of an educational
      monograph, demonstration of proper technique, and practice with the different
      devices. The program was evaluated by a randomized-control design. Assessment of
      practical skills included number of correct steps for the use of MDI (maximum
      score, 7), InspirEase (maximum, 7) and AeroChamber (maximum, 6). Theoretical
      knowledge was assessed with 25 multiple-choice questions. RESULTS: Pretest scores
      in the experimental group (n = 24) were 3.7 of 7, 1.9 of 7, and 0.3 of 6 steps
      correct for MDI, InspirEase, and AeroChamber devices, respectively, and 13 of 25
      for the theoretical knowledge assessment. The control group (n = 26) had similar
      pretest scores. After the program the experimental group significantly improved
      in all parameters: 6.3 of 7, 5.9 of 7, and 4.5 of 6 steps correct for MDI,
      InspirEase, and AeroChamber devices, respectively, and 18 of 25 questions correct
      (p < 0.01 for all parameters). CONCLUSIONS: Implementation of a simple
      educational program among pediatric residents can significantly increase their
      skills in the use of inhalational therapy.

PMID- 7722162
TI  - The natural history of exposure to the imported fire ant (Solenopsis invicta).
AB  - BACKGROUND: Imported fire ants (IFA) are a common cause of insect venom
      hypersensitivity in the southeastern United States. The purpose of this study was
      to determine the sting attack rate and development of specific IgE in an
      unsensitized population. METHODS: Study participants consisted of 137 medical
      students with limited exposure to IFA-endemic areas who were temporarily training
      in San Antonio, Tex. Subjects were surveyed for prior IFA exposure with a
      questionnaire, and IFA-specific IgE was evaluated with RAST and intradermal skin
      testing. Evaluations were performed on arrival and reported at departure from the
      endemic area 3 weeks later. RESULTS: One hundred seven subjects completed the
      study. Field stings were reported in 55 subjects, resulting in a sting attack
      rate of 51%. In these 55 subjects 53 (96%) reported a pustule or a small local
      reaction at the sting site, one (2%) reported an isolated large local reaction,
      and none reported a systemic reaction. At the 3-week follow-up skin test and RAST
      conversions occurred in seven subjects (13%) and in one subject (1.8%),
      respectively. CONCLUSIONS: Even brief exposures to IFA-endemic areas result in
      significant sting rates and concurrent rapid development of IFA-specific IgE in
      16% of stung subjects.

PMID- 7722163
TI  - The use of twice daily nedocromil sodium in the treatment of asthma.
AB  - The efficacy and safety of nedocromil sodium inhalation aerosol (4 mg of Tilade
      administered by metered-dose inhaler) given twice daily was compared with placebo
      in 112 patients with mild-to-moderate asthma who had been receiving maintenance
      therapy with oral or inhaled bronchodilators or both. After a 2-week run-in
      period and a subsequent 2-week baseline period, patients were randomized to
      active treatment (n = 56) or placebo (n = 56) for 8 weeks. All maintenance
      bronchodilators were withdrawn before the baseline period, and patients entered
      the treatment period only after demonstrating a specified level of asthma
      symptoms. Twice daily administration of nedocromil sodium improved all asthma
      symptoms in these patients who had symptoms as a result of the withdrawal of
      their maintenance theophylline and/or oral and inhaled beta 2-agonist
      bronchodilators. During the primary time period (treatment weeks 5 to 8),
      statistically significant between-group differences favored nedocromil sodium for
      the asthma summary score (primary variable, p = 0.001), daytime asthma (p =
      0.001), and sleep difficulty caused by asthma (p = 0.006). Furthermore,
      significant reductions in the use of as-needed rescue medications were reported
      in the nedocromil sodium group (p = 0.003) compared with the placebo group. Final
      overall opinions of treatment effectiveness expressed by physicians (p = 0.016)
      and patients (p = 0.002) strongly favored nedocromil sodium.

PMID- 7722164
TI  - Comparison of commercial peanut skin test extracts.
AB  - BACKGROUND: Skin prick testing is a major tool for diagnosing food allergy. Food
      allergen extracts have not been standardized; this may lead to great variability
      in the predictive accuracy of skin prick tests. METHODS: Six commercial peanut
      skin test extracts were compared in vitro with RAST inhibition assays, ELISA, and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by
      immunoblotting with sera from peanut-allergic adults and in vivo by skin prick
      testing. RESULTS: ELISA showed that the content of peanut allergens Ara h I and
      Ara h II in the extracts ranged from 0.0015 to 0.0236 and 0.0001 to 0.0164 mg
      Eq/ml, respectively. RAST inhibition studies showed that the extracts produced
      curves of similar slope, suggesting conservation of allergenic epitopes. SDS-PAGE
      revealed differences in protein profiles because roasted extracts generally
      possessed the same number and proportion of major protein bands but raw extracts
      varied more in both respects. SDS-PAGE and immunoblotting showed that two of the
      extracts contained major IgE-binding protein bands that did not appear in the
      others. One roasted extract gave little protein banding and consequently little
      IgE binding. CONCLUSIONS: Skin testing results showed no differences in the
      ability of the extracts to provoke a positive skin test response in peanut
      sensitive subjects.

PMID- 7722165
TI  - Prominent neutrophilic inflammation in sputum from subjects with asthma
      exacerbation.
AB  - To infer possible mechanisms of acute airway inflammation and mucus
      hypersecretion in acute severe asthma, we performed cellular and biochemical
      analysis on sputum from 18 adults with acute severe asthma and compared the
      results with results of analysis of sputum from 12 adults with cystic fibrosis
      (CF). We found that in subjects with asthma neutrophils made up more than 75% of
      sputum cells in 10 samples whereas eosinophils made up more than 75% of cells in
      only three samples. Fifty percent of the subjects with asthma reported that their
      asthma exacerbation was precipitated by a respiratory tract infection, and these
      subjects had a significantly higher percentage of neutrophils in their sputum
      (85% +/- 6% vs 57% +/- 12%, p = 0.05). In the CF samples neutrophils made up more
      than 95% and eosinophils less than 1% of cells in all samples analyzed. Analysis
      of fluid phase chemicals in asthmatic and CF sputum samples showed that despite
      overall lower mean values of neutrophil elastase (27 +/- 11 micrograms/ml vs 466
      +/- 121 micrograms/ml, p = 0.0001) and interleukin-8 (IL-8) (55 +/- 15 ng/ml vs
      186 +/- 24 ng/ml, p = 0.0001), some of the asthmatic samples had values for these
      variables that overlapped those in the CF samples. In addition, the asthmatic
      samples were distinguished by the presence of higher tryptase (10 +/- 7 U/L vs
      0.9 +/- 0.9 U/L, p = 0.0001) and interleukin-6 (1166 +/- 447 ng/ml vs 186 +/- 24
      ng/ml; p = 0.0001) levels and by a higher ratio of albumin to mucin-like
      glycoprotein (0.8 +/- 0.5 vs 0.1 +/- 0.002, p = 0.02). DNA levels were lower in
      the asthmatic samples (0.5 +/- 0.3 mg/ml vs 3.5 +/- 1.2 mg/ml, p = 0.05). We
      conclude that neutrophils predominate more frequently than eosinophils as the
      major inflammatory cell in sputum from patients with asthma in acute
      exacerbation. We speculate that this may be because respiratory tract infections
      are a frequent precipitant of acute asthma. In addition, the high IL-8 levels and
      free neutrophil elastase activity observed in asthmatic sputum suggests that IL-8
      may mediate airway neutrophilia in acute asthma and that neutrophil elastase may
      mediate mucin glycoprotein hypersecretion in acute asthma, as has been proposed
      for the mucin hypersecretion in CF.

PMID- 7722166
TI  - Effects of macrolide antibiotics on neurally mediated contraction of human
      isolated bronchus.
AB  - BACKGROUND: Long-term administration of macrolide antibiotic substances is an
      alternative therapy used in the treatment of asthma and airway
      hyperresponsiveness, but neither its mechanism of action nor whether this
      substance exerts an immediate action in the airways is known. METHODS:
      Contractile responses of human isolated bronchial strips to electrical field
      stimulation (EFS) and acetylcholine were assessed under isometric conditions in
      the absence and presence of erythromycin, roxithromycin, or clarithromycin.
      RESULTS: Incubation of tissues with erythromycin (3 x 10(-5) mol/L) attenuated
      the contractile responses to EFS so that the stimulus frequency required to
      produce 50% of the maximal contraction increased from 4.1 +/- 0.5 to 10.1 +/- 0.7
      Hz (mean +/- SE; p < 0.001). In contrast, contractile responses to acetylcholine
      were not changed. Erythromycin reduced the EFS-induced contraction in a
      concentration-dependent fashion; the maximal decrease from the baseline response
      was 92.8% +/- 3.6% (p < 0.001). This inhibitory effect was not altered by
      propranolol, indomethacin, ouabain, charybdotoxin, or mechanical removal of the
      epithelium. Roxithromycin and clarithromycin likewise inhibited neurally mediated
      contraction. CONCLUSIONS: These results suggest that macrolides may inhibit
      cholinergic neuroeffector transmission in the human airway smooth muscle,
      probably by reducing exocytotic release of acetylcholine from the nerve
      terminals.

PMID- 7722167
TI  - Reduced adenylyl cyclase activation with no decrease in beta-adrenergic receptors
      in basenji greyhound leukocytes: relevance to beta-adrenergic responses in airway
      smooth muscle.
AB  - Mononuclear leukocytes (MNLs) have been used as a model of beta-adrenergic
      responsiveness of airway smooth muscle, but the relevance of this model remains
      controversial. The basenji greyhound (BG) dog model of airway hyperresponsiveness
      shares some features with human asthma, and airway smooth muscle shows a
      selective impairment in isoproterenol-stimulated adenylyl cyclase activity. In
      this study, MNL membranes were obtained from these same dogs, and the beta
      adrenergic receptor-adenylyl cyclase cascade function was compared with that in
      airway smooth muscle. beta-Adrenergic receptor numbers and affinities for iodine
      125-cyanopindolol were similar in the two dog groups (receptor numbers [Bmax] =
      441 +/- 101 and 447 +/- 61 fmol/mg protein and dissociation constant [Kd] = 269
      +/- 44 and 312 +/- 60 pmol/L for mongrel and BG MNLs, respectively). Quantities
      of the Gs alpha protein were not different in the membranes as determined by
      immunoblotting. Stimulation of adenylyl cyclase by isoproterenol (100 mumol/L)
      was impaired in MNL membranes of BG membranes (22% +/- 4% increase over guanosine
      triphosphate [10 mumol/L]) compared with mongrel membranes (47% +/- 8.6% increase
      over guanosine triphosphate [10 mumol/L], p < 0.05). Stimulation of adenylyl
      cyclase by prostaglandin E1 (10 mumol/L), NaF (10 mmol/L), or forskolin (10
      mumol/L) did not differ in membranes from the two groups. No difference was found
      in the lymphocyte subsets in the two groups as determined by flow cytometry.
      These findings are qualitatively similar to studies of trachealis muscle
      membranes from these same dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722168
TI  - Detection of a novel macrophage-derived mucus secretagogue (MMS-68) in
      bronchoalveolar lavage fluid of patients with asthma.
AB  - BACKGROUND: We have previously described a novel high-molecular-weight macrophage
      derived mucus secretagogue (MMS-68) that causes mucuslike glycoconjugate release
      from cultured airways, nasal explants, and the Ishikawa adenocarcinoma cell line.
      We have generated monoclonal antibodies against MMS-68 and have developed an
      antigen-capture ELISA to measure MMS-68 levels in biologic fluids. Using this
      ELISA, we have demonstrated elevated levels of MMS-68 in the bronchoalveolar
      lavage fluid (BALF) of smokers and persons chronic bronchitis, in a patient with
      asthma and bronchorrhea, and in nasal lavage from patients with allergic rhinitis
      challenged with histamine and methacholine. We have also demonstrated that both
      spontaneous and lipopolysaccharide induced MMS-68 production is increased in the
      culture supernatants of monocytes from patients with steroid-dependent asthmas
      compared with those from normal control subjects. METHODS: To delineate further a
      role for MMS-68 in the regulation of mucus secretion in asthma, we measured MMS
      68 levels in the BALF of 37 patients with non-steroid-dependent asthma and of 16
      control subjects. RESULTS: There were 21 men and 16 women in the asthma group
      (age range, 17 to 62 years; mean, 33.8 years) and 11 men and five women in the
      control group (age range, 18 to 42 years; mean, 27.8 years). There were no
      statistical differences in either total cell count (145.5 x 103 +/- 75.7
      cells/mm3 x 10(3) cells/mm3 vs 134 x 103 +/- 65.9 x 10(3) cells/mm3, p < 0.234)
      or numbers of alveolar macrophages (103.7 x 10(3) +/- 71.7 x 10(3)/mm3 vs 98.7 x
      10(3) +/- 65 x 10(3) cells/mm3, p < 0.244) when the asthmatic group was compared
      with the control group. The MMS-68 level in the asthmatic group was 2.1 +/- 0.25
      micrograms MMS-68 per milligram protein compared with 2.09 +/- 0.26 micrograms
      MMS-68 per milligram protein (p < 0.256) in the control group. CONCLUSIONS: There
      was no correlation between MMS-68 levels and total protein content, numbers of
      alveolar macrophages, or the production of other macrophage-derived cytokines
      including interleukin-1, interleukin-6, or tumor necrosis factor in the asthmatic
      BALF. Mild asthma, which is clinically not associated with mucus hypersecretion,
      was not associated with elevated levels of MMS-68. We believe that direct
      correlation exists between mucus hypersecretion and MMS-68 levels.

PMID- 7722169
TI  - Identification of important allergens in German cockroach extracts by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis and western blot analysis.
AB  - BACKGROUND: Despite recent advances in the purification and characterization of
      cockroach allergens, identification of clinically important allergens and their
      source have not been completely elucidated. This study investigated the allergen
      content of German cockroach (Blattella germanica) whole body (GWBE) and fecal
      (GFE) extracts. METHODS: Sera from 37 subjects with asthma, with positive skin
      test results to cockroach, were used for RAST and Western blot (after sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE] under reducing
      conditions); this serum panel is the largest used to date for cockroach allergen
      analysis. RESULTS: RAST reactivity to GWBE and GFE were highly correlated (r =
      0.882, p < 0.001). SDS-PAGE and Western blotting showed that GWBE and GFE had
      similar patterns of IgE binding. Furthermore, Western blot inhibition
      investigations revealed that either GWBE or GFE could almost completely inhibit
      the reactivity of the other extract, SDS-PAGE and Western blotting demonstrated
      in both extracts numerous bands that displayed a high prevalence of IgE binding.
      Protein bands at 67, 50, 45, and 36 kd bound more than 50%, and the band at 60 kd
      bound approximately 80% of the sera tested. CONCLUSIONS: In summary, this
      investigation identified German cockroach allergens, established their relative
      importance by prevalence of reactivity to a large serum panel, and demonstrated
      that cockroach feces possess significant allergenic activity. Five allergens
      identified demonstrated reactivity with up to 50% to 80% of the 37 subjects' sera
      tested.

PMID- 7722170
TI  - Elevated IgE level in relationship to nutritional status and immune parameters in
      early human immunodeficiency virus-1 disease.
AB  - Elevation of IgE has been associated with T-cell dysregulation and with the
      occurrence of opportunistic infections in patients with acquired immunodeficiency
      syndrome. The precise cause of IgE overproduction during the early stages of
      human immunodeficiency virus (HIV)-1 disease, however, has not been established.
      In light of reports demonstrating that IgE production may be affected by vitamin
      E levels in an animal model, we evaluated nutritional status in relationship to
      plasma IgE levels and immune parameters in 100 asymptomatic HIV-1-seropositive
      and 42 HIV-1-seronegative homosexual men. Approximately 18% of the HIV-1
      seropositive population demonstrated biochemical evidence of plasma vitamin E
      deficiency (< 5 micrograms/ml). Subsequent analysis of available samples
      indicated a dramatic elevation of IgE levels (308 +/- 112 IU/ml) in vitamin E
      deficient seropositive subjects (n = 9) as compared with age and CD4-matched HIV
      1-seropositive persons with adequate vitamin E levels (n = 16, 118.1 +/- 41.1
      IU/ml) and significantly lower levels (59.5 +/- 15.7 IU/ml) in HIV-1-seronegative
      men (n = 20, p = 0.01). This effect, which was independent of CD4 cell count, did
      not appear to be influenced by atopic or gastrointestinal parasitic disease. The
      low plasma vitamin E levels were related at least in part to dietary intake (r =
      0.552, p = 0.01), suggesting that supplementation may be warranted in HIV-1
      infected persons in whom vitamin E deficiency develops. Analysis of covariance
      revealed a strong relationship between IgE levels and CD8 cell counts (p <
      0.006), and between IgE level and vitamin E deficiency (p < 0.039).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7722171
TI  - Interleukin-4 receptor expression by human B cells: functional analysis with a
      human interleukin-4 toxin, DAB389IL-4.
AB  - BACKGROUND: Studies of human IgE-secreting B cells have proven difficult because
      of the small size of this population. We have used an interleukin-4 (IL-4) fusion
      toxin to detect functionally IL-4 receptor (IL-4R) expression on B cells involved
      in IgE synthesis. METHODS: In diphtheria toxin IL-4 (DAB389IL-4) the receptor
      binding domain of diphtheria toxin has been replaced with human IL-4. DAB389IL-4
      cytotoxicity depends on IL-4R binding and internalization. RESULTS: Addition of
      DAB389IL-4 inhibited IgE synthesis induced by IL-4+ anti-CD40 monoclonal antibody
      or hydrocortisone. IgE inhibition resulted from DAB389IL-4 B-cell cytotoxicity
      because DAB389IL-4 inhibited IL-4-independent B-cell proliferation. Thus
      induction of human IgE synthesis involves IL-4R+ cells. In contrast, terminally
      differentiated, IgE-producing B cells no longer express functional IL-4R because
      DAB389IL-4 only modestly inhibited ongoing IgE synthesis by B cells from patients
      with hyper-IgE states and only minimally affected IL-4-induced IgE synthesis in
      normal B cells when the toxin was added at day 7. Pokeweed mitogen-induced IgM
      synthesis was sensitive to early but not to late addition of DAB389IL-4. Thus the
      loss of functional IL-4R immunoglobulin-secreting B cells is independent of
      isotype switching. CONCLUSIONS: IgE-secreting B cells no longer express
      functional IL-4R. Therapies for allergic disease that target the IL-4R would not
      affect IgE-secreting B cells but may block the recruitment of B cells into the
      IgE-secreting pool. For optimal benefits this approach may be combined with
      therapies that target IL-4R-, IgE-secreting B cells.

PMID- 7722172
TI  - Immune function in cigarette smokers who quit smoking for 31 days.
AB  - A group of 28 healthy, white, male, light-to-moderate smokers, 21 to 35 years of
      age, were offered a financial inducement to abstain from smoking for 31 days. A
      matched control group of 11 smokers were paid to continue smoking during the same
      period. Nonspecific parameters of immune system function were monitored before
      and at various times after smoking abstinence. Abstinence increased natural
      killer cell cytotoxic activity but did not alter mitogen-induced T-lymphocyte
      proliferation as measured by responses to concanavalin A or phytohemagglutinin.
      Serum cortisol concentrations also decreased after smoking cessation; however,
      changes in immune function were not correlated with serum cortisol change, nor
      with indices of smoking such as plasma nicotine and cotinine levels. Responses to
      concanavalin A and phytohemagglutinin were positively correlated with change in
      self-reported alcohol ingestion during smoking abstinence. Results indicate that
      elevation in natural kill cell cytotoxic activity is detectable within 1 month of
      smoking cessation, even in light-to-moderate smokers. However, elevation in
      natural killer cell cytotoxic activity appears not to be directly related to
      cessation-induced reductions in plasma nicotine, cotinine, or circulating
      cortisol levels.

PMID- 7722173
TI  - Delayed hypersensitivity to pollen skin prick tests and seasonal rhinitis.

PMID- 7722174
TI  - Toluene diisocyanate-induced reverse passive cutaneous anaphylaxis caused by IgG
      antibody.

PMID- 7722175
TI  - X-linked agammaglobulinemia presenting as transient hypogammaglobulinemia of
      infancy.

PMID- 7722176
TI  - Elevated serum tryptase in exercise-induced anaphylaxis.

PMID- 7722177
TI  - Sublingual immunotherapy for cat allergy.

PMID- 7722178
TI  - Breath-actuated metered-dose inhaler.

PMID- 7722179
TI  - Allergy to latex and papain.

PMID- 7722180
TI  - Dietitians as food and nutrition experts.

PMID- 7722181
TI  - Dietitians as food and nutrition experts.

PMID- 7722182
TI  - Dietitians as food and nutrition experts.

PMID- 7722183
TI  - More ideas for cooking chicken.

PMID- 7722184
TI  - ADA sends nutrition policy recommendations to the White House Conference on
      Aging.

PMID- 7722185
TI  - Mapping a course for the future. Dietetics leadership in the 21st century.

PMID- 7722186
TI  - The frail elderly: meeting the nutritional challenges.

PMID- 7722187
TI  - Thiamin status, diuretic medications, and the management of congestive heart
      failure.
AB  - OBJECTIVE: To assess the prevalence of thiamin deficiency in patients with
      congestive heart failure who are treated with diuretics that inhibit sodium and
      chloride reabsorption in the thick ascending limb of the loop of Henle (loop
      diuretic therapy). DESIGN: A cross-sectional investigation of thiamin status of
      consecutive patients with congestive heart failure being treated with loop
      diuretic therapy. SETTING: Cardiology clinic of a midwestern tertiary-care
      medical center. SUBJECTS: Thirty-eight patients were recruited (mean age +/-
      standard deviation = 55 +/- 14 years). Validation of methodology was conducted
      with nine age-matched control subjects. MAIN OUTCOME MEASURES: Thiamin status was
      assessed biochemically by in vitro erythrocyte transketolase activity assay.
      Assessment of dietary intake of thiamin was accomplished with a semiquantitative
      food frequency questionnaire. STATISTICAL ANALYSES PERFORMED: Fisher's exact test
      and logistic regression were used to evaluate relationships between thiamin
      status and variables of interest. RESULTS: Biochemical evidence of thiamin
      deficiency was found in 8 of 38 (21%) patients. Evidence of risk for dietary
      thiamin inadequacy was found in 10 of 38 patients (25%). Seven of the 8 patients
      with biochemical evidence of thiamin deficiency met study criteria for dietary
      adequacy, although quantified data suggested that only 4 of the patients achieved
      two thirds of the Recommended Dietary Allowance. Biochemical evidence of thiamin
      deficiency tended to be more common among patients with poor left ventricular
      ejection fractions (P = .07). CONCLUSIONS: Thiamin deficiency may occur in a
      substantial proportion of patients with congestive heart failure, and dietary
      inadequacy may contribute to increased risk.

PMID- 7722188
TI  - Urinary isoflavonoid phytoestrogen and lignan excretion after consumption of
      fermented and unfermented soy products.
AB  - OBJECTIVE: To compare the effects of consumption of fermented and unfermented soy
      products on excretion of urinary isoflavonoid phytoestrogens and lignans in
      healthy men. DESIGN: A randomized, crossover trial consisting of two 9-day
      feeding periods following 5 days of baseline data collection. SUBJECTS: Healthy
      men, aged 20 to 40 years, were recruited from the University of Minnesota Twin
      Cities community. Of the 22 subjects who began the study, 17 completed all
      feeding periods. INTERVENTIONS: Fermented soy product (112 g tempeh) or
      unfermented soy (125 g soybean pieces) was consumed during each controlled
      feeding period. MAIN OUTCOME MEASURE: Urine samples collected while subjects
      consumed their habitual diets and on the last 3 days of each feeding period were
      analyzed for isoflavonoid and lignan content by isotope dilution gas
      chromatography-mass spectrometry. STATISTICAL ANALYSIS PERFORMED: Comparisons of
      isoflavonoid and lignan excretion were analyzed using the general linear model
      procedure. Orthogonal contrasts were used to determine treatment differences of
      interest. RESULTS: Urinary excretion of isoflavonoids (equol, O
      desmethylangolensin [O-DMA], daidzein, genistein) was higher and excretion of
      lignans (enterodiol, enterolactone) was lower when subjects consumed soy
      supplemented diets than when they consumed their habitual diets (P < .05).
      Urinary isoflavonoid excretion and lignan excretion were similar when subjects
      consumed tempeh and soybean pieces diets; however, recovery of daidzein and
      genistein was significantly higher when subjects consumed the tempeh diet than
      when they consumed the soybean pieces diet (P < .002). When fed soy, 5 of 17
      subjects excreted high amounts of equol. These five subjects tended to excrete
      less O-DMA and daidzein than the 12 subjects who excreted low amounts of equol (P
      < .06). CONCLUSIONS: Fermentation of soy decreased the isoflavone content of the
      product fed but increased the urinary isoflavonoid recovery. This finding
      suggests that fermentation increases availability of isoflavones in soy.

PMID- 7722189
TI  - Utilization of home-delivered meals by recipients 75 years of age or older.
AB  - OBJECTIVE: To compare the effects of gender, age, and living situation on
      utilization of home-delivered meals by elderly recipients. DESIGN: Cross
      sectional cohort study. SETTING: The sample was recruited from five meals-on
      wheels agencies in southern Ontario, Canada, representing both rural and urban
      settings. SUBJECTS: Participants were 150 white, independently living recipients
      of meals-on-wheels who were older than 75 years and able to communicate in
      English and who had access to a telephone. Of these, 137 (90 women and 47 men)
      completed the study (attrition rate = 9%). MAIN OUTCOME MEASURES: Meal
      utilization: the energy and nutrient content and the amounts of specific foods in
      the consumed portions of delivered meals calculated as percentages of the total
      received from the service agencies. STATISTICAL ANALYSES PERFORMED: Two-factor
      analysis of variance. RESULTS: Meal utilization in terms of energy of the
      consumed portion of the delivered meals was 81 +/- 18%. Nutrient utilization
      ranged from 83% (vitamin A) to 77% (vitamin C). For specific foods, utilization
      ranged from 67% (miscellaneous) to 83% (protein sources and soups). Utilization
      levels for energy, eight nutrients, and specific foods were significantly higher
      for men than for women. Women living alone showed higher utilization values for
      energy and 11 nutrients compared with those living with others. Age had no effect
      on meal utilization. CONCLUSIONS: Monitoring and consultation procedures are
      necessary to ensure maximum nutritional benefits to clients and cost
      effectiveness of the meal service.

PMID- 7722190
TI  - Validation of a food habits questionnaire: poor performance in male manual
      laborers.
AB  - OBJECT: To examine the reliability and validity of a food habits questionnaire
      developed by Kristal et al in male manual laborers. DESIGN: A cross-sectional
      baseline survey. SETTING: The community of Ottawa-Carleton, Canada. SUBJECTS: All
      people working in non-office-based positions for two local governments were
      invited to a heart-health screening clinic. Male subjects (n = 362) who met risk
      factor eligibility criteria were interviewed and entered into the study. MAIN
      OUTCOME MEASURES: The food habits questionnaire developed by Kristal et al was
      the main focus of analysis. Additional outcomes included a food frequency
      questionnaire and risk factors for cardiovascular disease. STATISTICAL ANALYSES:
      Reliability was assessed using Cronbach's alpha and Pearson correlation
      coefficients; confirmatory factor analysis was also done. Validity assessment
      included partial correlations. RESULTS: Low internal consistency was found for
      the five subscales of the questionnaire (alpha = .13 to .53). Confirmatory factor
      analysis did not reveal the postulated five-factor (subscale) structure.
      Correlation of the subscale scores with dietary fat intake was low (r = -.09 to 
      .23), and none of these associations were statistically significant after
      adjustment for age, body mass index, and education. An alternative scoring system
      that treated the questionnaire as a unidimensional behavioral checklist produced
      a higher internal consistency (alpha = .70) and significant correlation with
      dietary fat intake (r = -.27). CONCLUSIONS: The psychometric properties and
      scoring of the food habits questionnaire need to be explored in additional
      populations before the questionnaire is adopted for general use.

PMID- 7722191
TI  - Variations in sensitivity, specificity, and predictive value of a dietary fat
      screener modified from Block et al.
AB  - OBJECTIVE: To evaluate the ability of a fat screener modified from Block et al to
      discriminate persons whose diets consist of 38% of kilocalories or more from fat
      from the remainder of the population. DESIGN: Sensitivity, specificity, and
      positive predictive value of the adapted screener were calculated. Percentage of
      kilocalories from fat was assessed by means of a semi-quantitative food frequency
      questionnaire. Three cutoff points from the fat screener were used to examine
      which best identified those whose diets consisted of 38% of kilocalories or more
      from fat. SUBJECTS: Nine hundred ninety-seven persons responded to a food
      frequency questionnaire sent to a random sample of 2,000 members of a health
      maintenance organization. RESULTS: Sensitivity and specificity varied depending
      on which cutoff point from the fat screener was used. Sensitivity reached a high
      of 83.3% and specificity reached a high of 92.1%, but the screener was never
      highly sensitive and specific simultaneously, and the results did not vary
      considerably by race. The screener had low rates of gross misclassification into
      quintiles (< or = 2.7%) and was more effective at classifying respondents into
      quintiles of total fat intake (64.9% to 85.5% classified in the same quintile)
      than into quintiles of percentage of kilocalories from fat (43.2% to 60.5%
      classified in the same quintile). CONCLUSIONS: The adapted fat screener may be
      used in conjunction with other dietary evaluation methods, but it exhibits
      insufficient sensitivity and specificity to be used as a single assessment
      method.

PMID- 7722192
TI  - Use of very-low-calorie diets in the treatment of obese persons with non-insulin
      dependent diabetes mellitus.
AB  - This article discusses the use of very-low-calorie diets (VLCDs) in the treatment
      of obese persons with non-insulin-dependent diabetes mellitus (NIDDM). Research
      using VLCDs with overweight participants with and without diabetes is reviewed.
      In both groups of participants, it has been shown that VLCDs used in combination
      with behavior therapy increase initial weight loss. However, to date, it has not
      been possible to develop treatment programs that maintain this weight loss long
      term. Neither intensive maintenance sessions nor intermittent VLCDs have been
      successful in maintaining the benefits of VLCDs long term. Thus, from the
      perspective of producing long-term weight loss, balanced low-calorie diets appear
      to be as effective as VLCDs. However, VLCDs may be useful in treating obese
      persons with NIDDM, because caloric restriction independent of notable weight
      loss has marked effects on glycemic control. Several studies have shown that just
      7 days of caloric restriction can produce dramatic improvements in glycemic
      control; moreover, VLCDs produce greater improvements in glycemic control than
      more moderate diets, even if weight losses are the same. Research is needed to
      explore new ways to use VLCDs and other approaches to caloric restriction in the
      treatment of obese persons with NIDDM.

PMID- 7722193
TI  - Nutrition management of patients with epidermolysis bullosa.
AB  - Epidermolysis bullosa (EB), a heterogeneous group of rare, inherited disorders,
      is manifested by recurrent blistering of the skin induced by the slightest
      trauma. Little information exists regarding the nutrition management of patients
      with EB. This study presents information on growth, identifies potential
      nutrition problems, and provides guidelines for nutrition management of persons
      with EB. Eighty patients attending a dermatology clinic for EB patients are
      described. Severity of disease ranged from mild blistering of the knees, elbows,
      and feet to extensive blistering and scarring of the skin and entire
      gastrointestinal tract. Of the 18 children with EB simplex, which is a mild form
      of the disease, 4 (22%) were at nutritional risk. None of the 13 adults with EB
      simplex were underweight and 8 (62%) were overweight. Of the patients with the
      more severe forms of EB, 27 of the 35 (77%) children with dystrophic EB and 4 of
      the 7 (57%) children with junctional EB were at risk for malnutrition. Of the 7
      adults with dystrophic EB, 6 (86%) were underweight. Common nutrition problems
      included protein-energy malnutrition, chewing and swallowing problems,
      constipation, anemia, and vitamin/mineral deficiencies. When nutrition care
      protocols address these problems, growth, development, and nutritional status can
      improve. For those with severe nutrition problems, gastrostomy feeding or similar
      nutrition therapies should be considered.

PMID- 7722194
TI  - Interaction of dietary factors with oral anticoagulants: review and applications.
AB  - This article reviews the published original sources of information on
      interactions of oral anticoagulants with dietary factors, points out deficiencies
      in our knowledge of these interactions, and suggests applications for this
      information in the clinical setting. As with many drug-nutrient interactions, the
      original references include a few experimental studies and many case reports.
      Deciding which interactions of oral anticoagulants with dietary factors are
      clinically relevant and determining the appropriate dietary prescription
      concerning each interaction involves, in most cases, an educated opinion rather
      than a conclusion based on extensive research. Enough information exists on the
      vitamin K content of foods and the quantity of vitamin K that alters coagulation
      status from the therapeutic range to provide the patient with advice concerning a
      group of foods to avoid and a group of foods to limit to one serving per day.
      With respect to other dietary factors that may interact with oral anticoagulants,
      the patient should be cautioned concerning supplements of vitamins A, E, and C
      and alcohol used chronically or ingested in large quantities.

PMID- 7722195
TI  - Plate waste and perception of quality of food prepared in conventional vs
      commissary systems in the Nutrition Program for the Elderly.

PMID- 7722196
TI  - Dieting and binge eating: which dieters are at risk?

PMID- 7722197
TI  - Outcomes of a worksite cholesterol education program over a 5-year period.

PMID- 7722198
TI  - Dietary guidance workshop helps tribal program cooks make changes.
AB  - Nutrition educators need to view tribal program cooks as important food and
      nutrition gatekeepers for their clients, families, and communities. They need to
      train these cooks using a variety of educational techniques, including culturally
      sensitive food preparation sessions and classroom activities to increase cooks'
      knowledge and skills, enhance their self-esteem, and improve their attitudes
      about cooking more healthfully.

PMID- 7722199
TI  - Nutrition and nonnutrition majors have more favorable attitudes toward overweight
      people than personal overweight.

PMID- 7722200
TI  - Demonstrating nutrition leadership by working with the media.

PMID- 7722201
TI  - Challenging the future of dietetics education and credentialing--dialogue,
      discovery, and directions: a summary of the 1994 Future Search Conference.

PMID- 7722202
TI  - Scope of practice for qualified professionals in diabetes care and education.

PMID- 7722203
TI  - Women and cohort studies.

PMID- 7722204
TI  - Women and cardiovascular disease: contributions from the Framingham Heart Study.
AB  - The Framingham Heart Study is one of the leading longitudinal cohort studies of
      cardiovascular disease in both men and women. Women have been included since
      study inception in 1948. The Study has provided a wealth of sex-specific
      information concerning coronary and cardiovascular disease incidence as well as
      the impact of multiple risk factors on disease occurrence. Risk factor prediction
      charts based on Framingham data can be used by physicians to determine an
      individual patient's probability of developing CHD or stroke. Investigations of
      factors unique to women, such as menopause and estrogen replacement, and factors
      of interest to women, such as weight cycling and smoking cessation, have been
      reported.

PMID- 7722205
TI  - The nurses' health study: a cohort of US women followed since 1976.

PMID- 7722206
TI  - The Massachusetts Women's Health Study: an epidemiologic investigation of the
      menopause.
AB  - This paper presents findings from the Massachusetts Women's Health Study (MWHS),
      one of the largest population-based studies of mid-aged women. A longitudinal
      study that followed a population-based cohort of women as they proceeded through
      menopause, the MWHS's goal was to describe their responses and to identify health
      related, life-style, and other social factors that affect this transition.
      Findings indicate that natural menopause appears to have no major impact on
      health or health behavior. The majority of women do not seek additional help
      concerning menopause, and their attitudes toward it are, overwhelmingly, positive
      or neutral. Physicians treating mid-aged women must be careful not to confuse
      "menopausal" symptoms with indicators of underlying disease or conditions
      unrelated to menopause.

PMID- 7722207
TI  - The evolution of the Women's Health Initiative: perspectives from the NIH.
AB  - The Women's Health Initiative (WHI) addresses some of the major health concerns
      of postmenopausal women. It is designed to test whether long-term preventive
      measures will decrease the incidence of cardiovascular disease, certain cancers,
      and fractures, and it seeks to find better predictors of future health and
      disease in older women. This report traces the evolution of the clinical trial
      and observational study (CT/OS) components of WHI from early planning in the
      1980s to the current status of the WHI CT/OS as an integrated, ongoing clinical
      study. Particular attention is directed to the antecedent planning meetings and
      feasibility studies that formed the underpinnings of the WHI. The issues of
      hormone replacement therapy and of the optimal diet for postmenopausal women were
      investigated for almost a decade prior to WHI. However, no studies of sufficient
      size and duration to confidently test the value and risks of these approaches
      were initiated because of the cost and insufficient political commitment. The
      initiation of WHI in 1991 represents the confluence of scientific need and
      capability with the social priorities to improve the health and welfare of women.

PMID- 7722208
TI  - The Black Women's Health Study: a follow-up study for causes and preventions of
      illness.

PMID- 7722209
TI  - Physical, mental, and reproductive health of Quebec women physicians.
AB  - In order to address the personal and professional characteristics as well as the
      physical, mental, and reproductive health of women physicians, a survey was
      mailed to a random sample of 3,000 women and men physicians in the province of
      Quebec, Canada. The data obtained from women physicians were compared with those
      from men physicians and with available data on a comparable subgroup of
      professional women. The sociodemographic and health data highlight the physical
      and mental health status of women physicians. These data, which provide a global
      picture of Quebec women physicians, indicate that in spite of the challenges,
      they seem to reconcile their professional and parental activities without major
      repercussions on their physical and mental health.

PMID- 7722210
TI  - The Women Physicians' Health Study: background, objectives, and methods.
AB  - A methodologically compelling reason to collect health-related data on physicians
      is that it is relatively reliable, easy, and cost effective data to collect.
      Physicians are capable of answering comparatively complex medical and nonmedical
      questions in a survey format, and most of these data are unavailable or difficult
      to obtain from other sources (eg, medical records). In addition, we will be able
      to recontact this cohort with relative ease, to determine, for example, the
      effect of time on health behaviors, counseling practices, and health status. This
      is the first large-scale study of the demographic and psychosocial
      characteristics as well as the health behaviors, health status, and counseling
      practices of women physicians. This study should help answer many important
      questions about women, physicians, and women physicians.

PMID- 7722211
TI  - Systemic endotoxin induces Fos-like immunoreactivity in rat spinal sympathetic
      regions.
AB  - Immunocytochemical detection of Fos protein was used to evaluate the activation
      of neurons in sympathetic preganglionic regions of rat spinal cord after systemic
      treatment with endotoxin. Administration of relatively low doses of bacterial
      lipopolysaccharide (LPS) to conscious rats caused transient hypotension and
      stress hormone elevation. Three hours after LPS injection, Fos protein was
      detected in large numbers of neurons throughout the thoracic spinal cord. Fos
      immunoreactive neurons were found in spinal cord segments T3-T13 in the four
      sympathetic preganglionic nuclei: the intermediolateral cell column (77.7%), the
      intercalated nucleus (10.6%), the central autonomic nucleus (10.1%) and the
      lateral funiculus (1.5%). These regions in control animals showed no Fos
      staining. We conclude that sublethal endotoxemia is a potent stimulus causing Fos
      expression in sympathetic preganglionic regions.

PMID- 7722212
TI  - Adenosine and glutamate modulate the cardiovascular responses of angiotensins II
      and III in the area postrema of rats.
AB  - The purpose of this study was to determine the interactions of the renin
      angiotensin system with adenosine and glutamate in the area postrema (AP) of
      rats. Male Sprague-Dawley rats were anesthetized with urethane. Adenosine,
      angiotensins (Ang) II, III and their antagonist 1,3-Dipropyl-8-p
      sulfophenylxanthine (DPSPX), [Sar1Ile7]Ang III and glutamate antagonist, L
      glutamic acid diethyl ester (GDEE) were microinjected into the AP of rats. Our
      results demonstrated that microinjection of DPSPX significantly attenuated the
      depressor and bradycardic effects of Ang II and III at low (9.6 pmol) and high
      dose (480 pmol) of Ang II in normotensive rats. To test the interaction of
      glutamate and renin-angiotensin system, we found that glutamate antagonist, GDEE,
      markedly lowered depressor and bradycardic responses of Ang II but did not
      influence Ang III in rats. On the other hand, microinjection of the Ang
      antagonist [Sar1Ile7]Ang III 10 min prior to the injection of adenosine
      significantly altered the cardiovascular effects of adenosine in the AP. In
      conclusion, the endogenous adenosine and glutamate may influence the renin
      angiotensin system on cardiovascular responses in the AP of rats.

PMID- 7722213
TI  - Neural mechanism of depressor responses of arterial pressure elicited by
      acupuncture-like stimulation to a hindlimb in anesthetized rats.
AB  - The effects of acupuncture-like stimulation of a hindlimb on renal sympathetic
      nerve activity (RNA) as well as mean arterial blood pressure (MAP) were examined
      in anesthetized rats. An acupuncture needle (diameter of 160 microns) was
      inserted into the skin of a hindlimb and underlying muscles to a depth of 5 mm
      and was twisted at about 1 Hz. Under deep anesthetic condition, in about 70% of
      trials, acupuncture-like stimulation for 60 s induced a decrease in MAP which was
      accompanied by a decrease in RNA. Acupuncture-like stimulation applied to the
      muscles alone, but not to the skin alone, induced inhibition of RNA and MAP.
      Transection of sciatic and femoral nerves ipsilateral to the hindlimb stimulation
      completely abolished the responses of RNA and MAP. The hindlimb stimulation
      excited the femoral and common peroneal afferent nerves. In spinalized animals,
      the hindlimb stimulation did not produce any changes in RNA and MAP. The results
      indicate that the decrease in MAP induced by acupuncture-like stimulation of a
      hindlimb is a reflex response. The afferent pathway is composed of hindlimb
      muscle afferents while the efferent pathway is composed of sympathetic
      vasoconstrictors including the renal nerves. Endogenous opioids may not be
      involved in the present reflex, because an intravenous injection of naloxone, an
      antagonist of the opioid receptors, did not influence the reflex.

PMID- 7722214
TI  - Peptide immunoreactivities in the ganglionated plexuses and nerve fibers
      innervating the human gallbladder.
AB  - The mammalian gallbladder is innervated by a well-developed intrinsic neural
      network. However, little is known about the neurochemistry and organization of
      the innervation of this organ in humans. The aim of this study was to analyze the
      distribution of immunoreactivity (IR) for the neuropeptides, vasoactive
      intestinal polypeptide (VIP), neuropeptide Y (NPY), tachykinins (TK) and
      calcitonin gene-related peptide (CGRP) in the human gallbladder by means of
      immunohistochemistry. Neuropeptide-IRs are found in neurons and processes of the
      two ganglionated plexuses, i.e., the innermost plexus located in the lamina
      propria at the base of the mucosal folds, and the outermost plexus situated
      within the fibro-muscular layer. In these two plexuses, VIP-, NPY- and TK-IRs are
      present in ganglion cells and varicose fibers, whereas CGRP-IR is confined to
      nerve processes. VIP-IR is present in most, if not all, neurons. NPY- and TK-IRs
      are also found in many neurons. The densities of the peptide-IR nerves in the
      mucosa are NPY and VIP > TK >> CGRP, and in the fibro-muscular layer are NPY >
      VIP and TK > CGRP. The vasculature is richly innervated by NPY-IR nerves, which
      are mostly perivascular. CGRP-, VIP- and TK-IR processes are found only
      occasionally around blood vessels and in a paravascular position. Double-label
      studies demonstrated that a large number of VIP-containing neurons expresses NPY-
      or TK-IR. On the other hand, all neurons positive for either NPY- or TK-IR are
      immunostained for VIP. In agreement with these findings, most of the NPY-IR
      fibers in the lamina propria and fibro-muscular layer contain VIP-IR, and
      numerous TK-IR fibers are positive for VIP. However, the perivascular NPY-IR
      processes do not contain VIP-IR, suggesting an extrinsic origin. In addition, a
      population of TK-IR processes contains CGRP-IR and presumably originates from
      extrinsic sources, since CGRP/TK-IR intrinsic neurons could not be detected in
      the gallbladder. Peptide-IRs have a similar distribution in the neck, body and
      fundus of the gallbladder. No peptide-containing endocrine/paracrine cells are
      observed in the epithelium. The presence of peptide-IRs in the ganglionated
      plexuses and the abundance of peptidergic innervation suggest that peptides exert
      their effects on gallbladder function by acting directly on tissue targets and
      influencing intrinsic ganglion cells. Furthermore, the co-localization of more
      than one peptide in the same neuron raises the possibility that peptides are co
      released upon stimulation and might interact at the same target.

PMID- 7722215
TI  - Beneficial effect of an ACTH4-9 analogue on experimentally induced diabetic
      autonomic neuropathy in the eye of the rat under general anaesthesia.
AB  - While peripheral polyneuropathy is a well-known complication in diabetes
      mellitus, and the subject of a great deal of study, the clinical importance of
      autonomic diabetic neuropathy is increasingly recognised. Using an animal model,
      where the pupil diameter of the eye serves as a parameter of autonomic function,
      we produced an age and weight curve of pupil diameter and studied the development
      of autonomic neuropathy in rats with streptozotocin-induced diabetes. We show
      that diabetic rats develop significantly (P < 0.009) smaller pupils compared with
      controls, most probably due to a defective sympathetic input, caused by
      sympathetic neuropathy. Treatment with the neurotrophic peptide Org 2766, a
      synthetic ACTH4-9 analogue, prevents the occurrence of this sympathetic
      neuropathy, as the pupil diameters in the ACTH4-9 analogue-treated group are
      significantly (P < 0.05) larger than the pupils of placebo-treated rats, and are
      comparable to the pupil diameters of the rats in the control group.

PMID- 7722216
TI  - Platelet-induced suppression of baroreceptor activity is mediated by a stable
      diffusible factor.
AB  - We have demonstrated recently that platelets aggregating in the carotid sinus
      decrease baroreceptor sensitivity. The goals of the present study were to
      determine whether platelet-induced suppression of baroreceptor activity is
      mediated by a diffusible, transferable factor and, if true, whether the factor is
      short-lived or stable. Baroreceptor activity was recorded from the isolated
      carotid sinus during slow ramp increases in nonpulsatile pressure in rabbits
      anesthetized with sodium pentobarbital. Intraluminal exposure of the carotid
      sinus to washed rabbit platelets resuspended in Krebs buffer (3-5 x 10(8)
      cells/ml) and activated by thrombin decreased baroreceptor activity significantly
      (n = 7, P < 0.05). Maximum baroreceptor activity recorded at a pressure of 140
      mmHg was reduced to 81 +/- 7% of the control maximum. Injection of cell-free
      supernatant obtained from filtered thrombin-activated platelets also suppressed
      baroreceptor activity to a similar extent after 10 min (n = 7) and after 2 h (n =
      5) of incubation when maximum baroreceptor activity was reduced to 84 +/- 5 and
      82 +/- 5% of the control maximum, respectively. The inhibitory influence of
      activated platelets and platelet supernatant on baroreceptor activity was still
      apparent after 10-60 min of heating (95 degrees C) (n = 5) and was reversible
      upon removal of platelets and supernatant from the sinus. The results indicate
      that activated platelets release a stable diffusible factor that suppresses
      baroreceptor activity. We speculate that this 'inhibitory factor' may contribute
      to impairment of the baroreceptor reflex and neurally-mediated increases in
      arterial pressure in atherosclerotic and thrombotic states.

PMID- 7722217
TI  - Changes in medullary extracellular pH, sympathetic and phrenic nerve activity
      during brainstem perfusion with CO2 enriched solutions.
AB  - Measurements are presented of sympathetic nerve activity (SNA), phrenic nerve
      activity (PNA), and local extracellular pH (ECF pH) within the rostral
      ventrolateral medulla (RVLM) in response to perfusions of the RVLM with CO2
      enriched saline. Experiments were performed on cats anaesthetized with
      chloralose. The ventrolateral medullary surface was exposed, and a catheter was
      placed in the left vertebral artery from the axilla to allow perfusion of the
      RVLM. Baroreceptor and peripheral chemoreceptor denervations were performed by
      cutting the vagal, aortic and carotid sinus nerves. The activities of the renal
      and the phrenic nerve were recorded, in some experiments in parallel with the
      cardiac nerve. Recordings of the pH were done with ion-sensitive theta
      microelectrodes. A linear relationship between the CO2 concentration of the
      perfusate and the evoked changes in ECF pH was found. The ECF pH did not change
      systematically in one or the other direction within depths between 1 and 3 mm
      below the surface of the medulla. The various patterns of interaction of ECF pH,
      SNA, and PNA are described in detail. Phrenic nerve response to perfusions was
      very variable; a more prolonged increase in amplitude of phasic discharges
      compared to the duration of changes in SNA and ECF pH was the most frequent
      finding, but non-phasic tonic activation and complete silence were also seen
      during perfusions. SNA could also deviate from ECF pH both with regard to its
      latency and to its time course in response to perfusions. Therefore, this study
      provides further evidence for deviations of cardiorespiratory adaptation from ECF
      pH, corroborating the notion that this parameter is not the decisive one for
      central chemoreception.

PMID- 7722218
TI  - Effects of chemical stimulation of the rostral and caudal ventrolateral medulla
      on cerebral and renal microcirculation in rats.
AB  - We investigated the effects of neurons in the rostral and caudal ventrolateral
      medulla (RVL and CVL) on cerebral and renal microcirculation in rats. Rats were
      anesthetized with chloralose, paralyzed with tubocurarine, and artificially
      ventilated. Cerebral and renal blood flows (CBF and RBF) were measured
      simultaneously using laser-Doppler flowmetry. Chemical stimulation of the RVL
      neurons by microinjection of the excitatory amino acid L-glutamate increased
      arterial pressure (AP), whereas that of the CVL neurons decreased AP. Stimulation
      of the RVL neurons also elicited a stimulus-locked increase in CBF and a decrease
      in RBF. The percent change in CBF and RBF was dose-dependent as stimulus
      intensity was increased. Cerebral and renal vascular resistance (CVR and RVR)
      levels were calculated from changes in CBF or RBF and changes in mean AP. The
      percent reduction in CVR and percent elevation in RVR were also dose-dependent.
      Chemical stimulation of the CVL neurons elicited a stimulus-locked decrease in
      CBF and an increase in RBF. The percent reduction in CBF and percent elevation in
      CVR were dose-dependent. The percent reduction in RVR was also dose-dependent,
      while the percent elevation in RBF was not significant. Blood withdrawal reduced
      AP by a similar degree to CVL stimulation, but did not significantly decrease
      CBF. The results suggest that RVL and CVL neurons integrate cerebral and systemic
      microcirculation.

PMID- 7722219
TI  - Heart rate variability after complete autonomic blockade in man.
AB  - In a number of studies, using the autoregressive model for frequency domain
      analysis of R-R interval fluctuations, the low frequency (LF) component (centered
      at about 0.1 Hz) is claimed to index sympathetic activity level. The aim of this
      study was to investigate the mediation mechanism of the LF component by
      pharmacological blockade. Our results support earlier findings, obtained with the
      use of fast Fourier transformation, that in supine subjects spectral components
      of R-R interval variability at around 0.1 Hz are mediated mainly by cholinergic
      mechanisms. Therefore, the use of the LF component as sympathetic index appears
      questionable.

PMID- 7722220
TI  - Comparison of immunohistochemical localization of [Met5]enkephalin-Arg6-Gly7
      Leu8, [Met5]enkephalin, neuropeptide Y and vasoactive intestinal polypeptide in
      the superior cervical ganglion of the rat.
AB  - The localization of [Met5]enkephalin-Arg6-Gly7-Leu8 and [Met5]enkephalin
      immunoreactivities was studied in the rat superior cervical ganglion. The
      distribution of these enkephalin-containing peptides in the ganglion was
      correlated to that of neuropeptide Y and vasoactive intestinal polypeptide. Three
      different populations of peptide-containing postganglionic neurons were
      demonstrated. (1) A minor population (10-20%) of principal neurons was
      immunoreactive for [Met5]enkephalin-Arg6-Gly7-Leu8 but not immunoreactive for
      neuropeptide Y nor vasoactive intestinal polypeptide. (2) The major population
      (about 50-70%) was immunoreactive for neuropeptide Y but not for [Met5]enkephalin
      Arg6-Gly7-Leu8. (3) Few vasoactive intestinal polypeptide-immunoreactive
      principal neurons (less than 2% of all principal neurons) were observed in the
      ganglion. All vasoactive intestinal polypeptide-immunoreactive neurons were also
      immunoreactive for neuropeptide Y but not for [Met5]enkephalin-Arg6-Gly7-Leu8.
      [Met5]enkephalin-Arg6-Gly7-Leu8- and [Met5]enkephalin-immunoreactive nerve fibers
      had a similar distribution. These enkephalin immunoreactive nerve fibers were
      seen to enclose both neuropeptide Y-containing principal neurons and neurons
      devoid of neuropeptide Y immunoreactivity. Furthermore, there were enkephalin
      immunoreactive fiber baskets around vasoactive intestinal polypeptide
      immunoreactive neurons and sometimes also around solitary enkephalin
      immunoreactive neurons. Previously reported diverse role of enkephalins in the
      rat superior cervical ganglion is supported by this study.

PMID- 7722221
TI  - [Interleukin-6 and other cytokines in the aqueous humor in uveitis and
      endophthalmitis].
AB  - We studied aqueous humour and serum level of 4 cytokines during uveitis and
      endophthalmitis: Interleukin 6, Gamma interferon, tumor necrosis factor and
      Granulocyte-macrophage colony stimulating factor. High levels of IL-6 were found
      in aqueous humour during ocular inflammation and infection. This elevation of IL
      6 level was more constant and more important in the endophthalmitis group (mean
      level 2.992 pg/ml) than in the uveitis group (mean level 1.480 pg/ml). During
      endophthalmitis no evident relation was found between IL-6 level and clinical
      course or aspect, or bacteriological results of anterior chamber tapes. In the
      uveitis group, no relation was found between IL-6 level and clinical aspect or
      aetiology.

PMID- 7722222
TI  - [Acanthamoeba keratitis. Apropos of 2 cases].
AB  - Acanthamoeba keratitis is a rare pathology which is currently observed with
      increasing frequency in France. Two new cases are reported in young patients
      wearing soft hydrophile contact lenses. One patient apparently followed cleansing
      instructions, but the other did not. The essential parasitological diagnosis was
      confirmed rapidly after comeal sampling, but had been highly suspected from the
      clinical symptomatology. Treatment combining propamidine and eye-drop antibiotics
      led to recovery in both cases. Anatomical damage was however observed in one case
      and a penetrating graft was necessary.

PMID- 7722223
TI  - [Keratoconus and familial topographic corneal anomalies].
AB  - PURPOSE: Computer-assisted corneal topography, allows the detection of early
      abnormalities, including abortive or subclinical forms of keratoconus. So, it is
      possible to identify affected individuals with variable degrees, in family
      members of patients with keratoconus, to draw pedigrees, and to specify the mode
      of inheritance. METHODS: Computer-assisted digital videophotokeratoscope was used
      to map the corneas of 106 family members of 30 patients with keratoconus.
      RESULTS: Abnormalities observed included the inferior cornea markedly steeper
      than the superior cornea (I-S - 0.86 +/- 0.44 D) and a marked difference between
      the central corneal powers of the two eyes (delta PC = 0.72 +/- 0.22 D). However,
      there was no statistical difference with normal individuals for central corneal
      power. CONCLUSION: Pedigree analysis in these families suggests, in 50% of them,
      an autosomal dominant mode of inheritance. However, it is impossible to conclude
      for the other families, because of an insufficient number of cases.

PMID- 7722224
TI  - [Choroid metastases].
AB  - PURPOSE: The aim of the present study is to investigate the clinical features and
      the risk factors characteristic of choroidal metastasis, which is known as the
      most common malignant neoplasm of the adult eye. METHODS: A systematic
      ophthalmologic examination together with angiography and echography were
      performed in 106 patients with carcinoma. RESULTS: 10% of patients showed
      choroidal metastasis. Breast and bronchogenic carcinoma were the most common
      primary tumor. 82% of cases died within a mean 6.5 months. Clinical,
      angiographic, echographic and histopathologic features of such metastasis were
      described. CONCLUSIONS: The importance of an early diagnosis of such metastasis
      are raised.

PMID- 7722225
TI  - [The Farnsworth-Munsell 100 Hue test in the Bantu population. Preliminary
      results].
AB  - The purpose of this work was to establish in this first report the age standards
      of the Farnsworth-Munsell 100 hue in Zaire. The Farnsworth-Munsell 100 Hue test
      was performed in 132 normal subjects. All subjects were Zairian blacks aged from
      20 to 49 years. The test was administered binocularly, once, to each subject.
      Subjects were divided in three age groups. The first age group had 35 subjects
      aged between 20 and 29 years, the second age group had 48 subjects aged between
      30 and 39 years and the third 49 subjects aged between 40-49 years. The total
      error scores were 7.06 +/- 2.10 for the first age group, 9.03 +/- 1.80 for the
      second age group and 9.80 +/- 2 for the third age group. These results were aged
      related (r = 0.42, p inferior to 0.05). Scores of Zairian subjects in this study
      were higher when compared to those reported in Europe and U.S.A. Interpretation
      of results of the Farnsworth-Munsell 100 hue test must take in account this
      difference in ethnic origin.

PMID- 7722226
TI  - [Young glaucomatous patients in the Togo population].
AB  - Glaucoma in Blacks presents different epidemiological aspects from those
      classically described in Whites. For example, the prevalences are higher in
      Blacks than with Whites. This study concerning young togolese with chronic open
      angle glaucoma noted that 66.87% were less than 45 years old, of whom 7.25% were
      between 11-15 years; 23.85% between 15-24 years; 28.44% between 25-34 years and
      39.44% between 35-44 years; 65.23% were men and 34.86% female. The mean disc
      cuppings were 0.50 between 11-15 years; 0.52 between 15-24 years; 0.52 between 25
      34 years and 0.52 between 35-44 years (p = 0.6053, not significant). These
      cuppings were greater in the left eye than in the right (p < 0.02 with
      significance); in the left eye the values of the cuppings were 0.52 between 11-15
      years; 0.57 between 15-24 years; 0.67 between 25-34 years and 0.58 between 35-44
      years, while these values in the right eye were 0.50 between 11-15 years; 0.52
      between 15-24 years; 0.52 between 25-34 years and 0.52 between 35-44 years.
      Regarding the automated visual fields, the results correlated with the disc
      cuppings. The Togolese glaucomatous patients are often young with severe glaucoma
      characterized by major cuppings and very damaged visual fields.

PMID- 7722227
TI  - [Trilateral retinoblastoma: clinical and diagnostic imaging].
AB  - A case of trilateral retinoblastoma in a male child of 29 months is described,
      using a clinical and imaging approach. The patient was first presented with a
      proptosis, more pronounced in the left eye and with signs of a bilateral
      glaucoma. Ophthalmologic examination, echography and computed tomography were
      used to confirm the diagnosis. The importance of clinical examination associated
      with an imaging approach to evaluate intraocular tumors was emphasized and also
      the necessity of identifying trilateral retinoblastoma as a distinct entity and
      to differentiate it from intracranial metastasis or from a single retinoblastoma
      associated with pineal tumors.

PMID- 7722228
TI  - [Primary conjunctival-palpebral lymphedema and Milroy disease].
AB  - An 18-year-old girl had swelling of both upper and lower extremities due to
      chronic hereditary lymphoedema. She had bilateral eyelid and conjunctival
      lymphoedema. This is an ocular manifestation of Milroy's disease: primary and
      secondary forms of lymphoedema may occur and are discussed.

PMID- 7722229
TI  - [Attention: the modification of the pH of 5-fluorouracil (5-FU) makes it
      inappropriate for subconjunctival injection].

PMID- 7722230
TI  - [Orbital decompression by the Olivari technique].
AB  - Orbital decompression using Olivari's method is described: extraconal fat is
      removed surgically from the orbit. Intraconal fat is also removed with the help
      of a microscope. Removal of at least 5 cc of orbital fat is necessary to reduce
      exophthalmos. Usually between 5 cc to 10 cc of fat are removed.

PMID- 7722231
TI  - [Albinism].

PMID- 7722232
TI  - [Diabetic maculopathy].

PMID- 7722233
TI  - [Complementary tests in the surveillance of a treatment method with synthetic
      antimalarials].

PMID- 7722234
TI  - [Pilot study of transscleral light coagulation of retinal breaks using diode
      laser].
AB  - PURPOSE: We conducted a pilot trial to evaluate the efficacy and safety of
      transscleral diode laser photocoagulation in the management of retinal breaks.
      MATERIAL AND METHODS: Fourteen patients (14 eyes) were enrolled in the study.
      Twelve patients showed opaque media which prevented transpupillary argon laser
      photocoagulation (10 eyes) and/or a retinal detachment after previous failed
      surgery (3 eyes), and/or retinal tears with a curled and fixed posterior edge (6
      eyes). Twenty five retinal breaks were treated in the 14 eyes (7 breaks in
      attached retina and 18 in detached retina). RESULTS: A satisfactory
      retinochoroidal scar with permanent sealing of the retinal breaks was achieved in
      all eyes. The retina was attached in all eyes. The follow-up ranged from 2 to 12
      months. Ten patients had a minimum 6 month-follow-up. Overtreatment attributed to
      technical mistake occurred in two eyes. It has no adverse effect on the final
      result. CONCLUSION: Transscleral diode laser photocoagulation of retinal breaks
      is efficacious and safe. It is a valuable alternative to cryo treatment in eyes
      at high risk of postoperative PVR and/or when argon laser photocoagulation cannot
      be used, and/or in retinal detachments after previous failed surgery.

PMID- 7722235
TI  - [Treatment by refractive photokeratectomy of undercorrections after radial
      keratotomy].
AB  - Residual myopia after radial keratotomy is one of the major problems of this
      technique, it may be corrected with laser keratectomy. MATERIALS AND METHODS: We
      present the results of nine eyes treated with photorefractive keratectomy, due to
      undercorrection after radial keratotomy. The photoablation was performed with the
      laser VISX 20/20, wavelength 193 mm, and concerned a residual spherical
      equivalent myopia (after RK) with an average of -2.00 diopters and a range of
      0.87 to -3.75 D. RESULTS: Six months postoperatively, the average spherical
      equivalent refraction was no greater than -0.75 D and a range of -0.25 D to -2.12
      D; 66.7% were within +/- 0.5 D of emmetropia, with a uncorrected visual acuity >
      10/20. The best corrected visual acuity remained nearly the same. Postoperatively
      functional symptomatology and healing processus are comparable to the first
      intention of photoablation. CONCLUSION: The safety and effectiveness of laser
      Excimer photoablation seem to be demonstrated and this procedure could be used to
      complement RK.

PMID- 7722236
TI  - [Eye injuries in children aged 0 to 15 years. Apropos of 63 clinical reports].
AB  - Retrospective study of children eye injuries in 0 to 15 year-old children through
      a daily consultation over 4 years (from january 1986 to december 1989) in Yeelen
      Center in Sikasso (Mali) shows these facts: boys were more affected than girls;
      Children of 6 to 10 years were the most exposed; Eye injuries were more frequent
      and more severe in urban areas than in rural areas; the injuries of the lens, the
      hyphemas and the cornea were the most frequent and most strinking blind.

PMID- 7722237
TI  - [Treatment of strabismus with botulinum toxin].
AB  - Having used botulinum toxin for four years, we describe our experience in one
      hundred squinting patients and compare our results with the literature. We have
      good results in unilateral sixth nerve palsy and small deviations with binocular
      potential. Botulinum toxin can also be helpful in third and fourth nerve palsy,
      in Graves' ophthalmopathy, as an adjunct to transposition surgery and in cases of
      under- or overcorrections after surgery. In cases of muscle fibrosis and wide
      angle strabismus, the results are more disappointing. We describe an original
      method of conditioning the toxin in individual doses which eases the botulinum
      consultation processing.

PMID- 7722238
TI  - [Methods for screening and surveillance of diabetic retinopathy].
AB  - PURPOSE: The aim of this study is to investigate the various tests which allow to
      detect and follow-up diabetic retinopathy (DR). METHODS: Sixteen patients without
      DR or with background retinopathy underwent, once every six months: a full
      ophthalmologic investigation; a fluorescein angiography; a color vision test; a
      central visual field investigation. RESULTS: The impairment of angiography
      preceeded damage of eye fundus in 27% of cases. Deficiency of color vision and
      visual field were found in 57% of cases and in 35% respectively. These preceeded
      the appearance of angiographic DR in 50% of cases and 32% of cases respectively.
      CONCLUSION: The importance of such tools in the evolution of DR especially in
      young diabetics is discussed.

PMID- 7722239
TI  - [Control of intensity of light coagulation by thermo-induced release of a
      fluorescent marker encapsulated in liposomes. In vivo/ex vivo preliminary study].
AB  - PURPOSE: The aim of this in-vivo/ex vivo study was to assess the possible use of
      temperature sensitive liposomes in an established model such as the liver as a
      new approach to monitor the temperature induced by a laser. METHOD: Temperature
      sensitive liposomes (DSPC: DiStearoylPhophatidyl-Choline: critical temperature:
      55 degrees C) loaded with carboxy-fluoresceine were prepared by the Bancham
      procedure. These liposomes (1 ml solution) were injected to adult male wistar
      rats. Two hours later, the liver was exposed and irradiated with a 100 W Nd: YAG
      laser (single pulse mode, pulses ranging from 100 to 260 ms, spot diameter: 4
      mm). Simultaneously, the surface temperature was recorded with a infrared
      thermographic camera (Aga). The fluorescence emission was then measured with a
      fluorescent imaging system (Hamamatsu). RESULTS: The dye was released in response
      to laser energy. The amount of the drug release increased linearly with
      increasing temperature in the range 42 to 60 degrees C. The estimated latency of
      release seems more related to the heating pattern (i.e. to laser parameters) than
      to the liposomes. CONCLUSION: This preliminary study assesses the possible use of
      laser-induced release of liposome-encapsulated dye to monitor tissue temperature
      and then thermal damage.

PMID- 7722240
TI  - [Hyperplasia and sebaceous adenoma of the caruncle and conjunctiva].
AB  - A 61-year-old man was seen with an hyperplasia of the right caruncle and a
      conjunctival tumor localized under the left caruncle. Excision indicated a
      sebaceous benign origin. The patient suffered of a sicca syndrome with chronic
      inflammation of the conjunctiva.

PMID- 7722241
TI  - [Neurological complications of zona. Apropos of a case].
AB  - A 70 year old woman had left sixth nerve palsy, following an ophthalmic zona.
      Later she had controlateral hemiplegia with expression aphasia. Corticosteroid
      therapy improved the situation. The pathogenesis of this complication is
      discussed in this article. Ischaemic vasculitis is now a well known complication
      of herpes zoster which has already appeared in the literature. The case presented
      was related to ischaemia of the anterior artery of the troncus infero-lateral of
      Heubner's artery confirmed by further exploration.

PMID- 7722242
TI  - [Vitreoretinal proliferation. I. Clinicopathological aspects].
AB  - Proliferative vitreoretinopathy (PVR) remains the major complication occurring
      after a rhegmatogenous retinal detachment, and often results in massive
      periretinal retraction which makes impossible any attempt in reattaching
      neuroepithelial layers. The most recently proposed classifications of PVR as well
      as clinical observations improved the understanding of PVR and suggested that
      some events could be of striking importance in its development, such as the size
      of retinal breaks, eventual haemorrhages or overdosed cryoapplications. Most
      interesting findings, however, resulted from the more and more powerful analysis
      of vitreoretinal membranes. Electron microscopy, immunohistochemistry and
      molecular biology techniques permitted identification of a wide variety of
      cellular and biological components. The majority of cells involved in PVR are
      from retinal or ciliary pigment epithelial, glial or inflammatory origins.
      Extracellular matrix are constituted with collagen, fibronectin, heparan sulfates
      or laminin, but they also contain growth factors, immunoglobulins and activated
      complement. Moreover, proliferating cells express membrane receptors to growth
      factors and to immunocompetent cells, which makes PVR an extraordinarily
      complicated biological syndrome, involving a wide range of mediators and cellular
      systems.

PMID- 7722243
TI  - [Vitreoretinal proliferation. II. Pathogenic hypotheses].
AB  - The pathogenesis of proliferative vitreoretinopathy remains poorly understood and
      a large variety of hypotheses have been developed in an attempt to investigate
      cellular proliferations that follow rhegmatogenous retinal detachment. Several
      growth promoting factors have been identified within the vitreous body and
      proliferative membranes from patients with PVR. Their enzymatic, chemotactic,
      mitogenic or proinflammatory properties make them good candidates, either alone
      or more probably in a synergistic manner. They may be involved at different
      levels in the successive stages of PVR, cell migration, proliferation or
      vitreoretinal contraction. Numerous ocular and even extra-ocular structures may
      be involved as retina, pigment epithelium, ciliary body and serum, contain large
      amounts of these growth factors. Immune mediated inflammatory reactions have also
      been described and vitreoretinal strands exert additional mechanical effects.
      Current pathogenetic hypotheses suggest that PVR results from a wound healing
      process induced by retinal breaks and detachment of the neuroepithelium, when is
      reached a threshold of biological stimulation. Cell proliferation is
      unfortunately often overstimulated and the proliferating cells invade the
      vitreous cavity. If surgery is not capable of efficiently blocking the
      proliferation, it will be autostimulated and lead to a complete vitreoretinal
      retraction.

PMID- 7722244
TI  - [Laser spot diameter, pitfalls and dangers of unadapted choices].

PMID- 7722245
TI  - [Light coagulation in pre-proliferative diabetic retinopathy].

PMID- 7722246
TI  - Acute neurovascular complications with supracondylar humerus fractures in
      children.
AB  - We retrospectively reviewed 200 pediatric patients with acute type 3 extension
      type supracondylar fractures. Nineteen patients with nerve injuries were
      identified representing a 9.5% incidence of associated neurologic injury. All
      were associated with closed supracondylar fractures. The nerve injuries included
      seven anterior interosseus nerve palsies, four median nerve palsies, five radial
      nerve palsies and three ulnar nerve palsies. There were five vascular injuries,
      one was associated with a median nerve palsy. Three of these five patients
      required open exploration and one of these required arterial bypass. All other
      patients were treated with closed reduction and percutaneous pin fixation.
      Anterior interosseus nerve injury was the most common nerve injury in this series
      of pediatric supracondylar fractures. Diagnosis of this lesion may be subtle and
      was made in a delayed fashion in two patients in this series. Return of function
      occurred in all patients 6 to 16 weeks after the injury without surgical
      intervention. Anterior interosseus nerve injury may be more common than
      previously recognized and warrants a careful initial neurologic examination to
      identify this lesion.

PMID- 7722247
TI  - Normal arborization of the deep branch of the ulnar nerve into the interossei and
      lumbricals.
AB  - Ten adult hands were dissected to reexamine in new detail the distribution of the
      deep branch of the ulnar nerve from its origin in the ulnar tunnel to its
      termination in the first dorsal interosseous muscle. The relationships of the
      subdividing branches to each other and to the muscle bellies were clarified. The
      palmar interossei along with the first and second dorsal interossei were all
      innervated within the middle third of their corresponding metacarpal. The third
      and fourth dorsal interossei were innervated within the proximal third of their
      corresponding metacarpals, and the third lumbrical was innervated within the
      middle third whereas the fourth lumbrical was innervated along its distal third.

PMID- 7722248
TI  - Transforming growth factor-beta: possible roles in Dupuytren's contracture.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional polypeptide that
      stimulates extracellular matrix deposition and fibroblast proliferation. Because
      both these features characterize Dupuytren's contracture, we investigated a
      possible role for TGF-beta in the etiology of this disorder. We studied receptor
      expression for TGF-beta, effects of TGF-beta 1 on DNA-synthesis, and in vitro
      production of TGF-beta 1 and TGF-beta 2 in both normal and Dupuytren-derived
      fibroblasts. We also studied the effects of epidermal growth factor (EGF) on
      growth of the different cell types. TGF-beta receptor profiles were different
      between the two cell types, as were TGF-beta 1 and EGF-induced stimulation of
      cell growth. Both cell types secreted both active and latent TGF-beta. Our
      results suggest that growth factors such as TGF-beta and EGF may play a role in
      Dupuytren's contracture.

PMID- 7722249
TI  - Dupuytren's disease, carpal tunnel syndrome, trigger finger, and diabetes
      mellitus.
AB  - A comparative prospective study of 120 adult diabetics (60 insulin dependent, 60
      non-insulin dependent) and 120 non-diabetic adults as controls showed
      significantly higher incidence of Dupuytren's disease, limited joint motion,
      carpal tunnel syndrome, and flexor tenosynovitis in the diabetic population. Of
      the diabetic patients one third had a mild non-progressive form of Dupuytren's
      disease, which commonly involved the long and ring rays. Limited joint motion was
      noted in a third of diabetics, and carpal tunnel syndrome was observed in 15-25%,
      and flexor tenosynovitis in about a fifth. Limited joint motion co-existed with
      Dupuytren's disease in 57% of insulin-dependent diabetics. Diabetic
      polyneuropathy was found in two thirds of insulin-dependent diabetics and in one
      third of non-insulin dependent diabetics. All these hand changes were more marked
      in insulin-dependent diabetics and they showed a positive correlation with
      increasing age of the patient, duration of the diabetes, and the presence of a
      microangiopathy.

PMID- 7722250
TI  - Uncemented total wrist arthroplasty.
AB  - We report our experience with a non-cemented wrist implant we developed in 1986.
      Between 1986 and 1991, 50 prostheses were implanted in 45 patients, 33 with
      rheumatoid arthritis and 12 with traumatic arthritis. After an average of 4.5
      years (range, 2-6 years), we evaluated pain, daily activities, motion, grip
      strength, and x-ray films. The results were excellent in 24 wrists, good in 12,
      fair in 5, and poor in 8.

PMID- 7722251
TI  - Proximal interphalangeal joint silicone replacement arthroplasty: clinical
      results using an anterior approach.
AB  - Sixty-nine proximal interphalangeal joint silicone arthroplasties in 36 patients
      inserted through an anterior approach were reviewed. Average followup time was
      3.4 years. The average extension deficit was slightly improved from 17 degrees to
      8 degrees, but the total active motion (active flexion minus active extension)
      did not significantly increase (44 degrees to 46 degrees). Coronal plane
      deformities were not successfully corrected. Pain relief was obtained in 67 of 69
      digits. There were 12 digits with complications, and five implants fractured. The
      anterior approach allows preservation of the central slip insertion and
      initiation of immediate active and passive joint motion. With proper indications,
      careful surgical technique, and a supervised therapy protocol, proximal
      interphalangeal joint silicone arthroplasty is a useful operation for pain relief
      and functional gain.

PMID- 7722252
TI  - Opening versus closing wedge osteotomy of the curved ulna in radial clubhand.
AB  - The use of an opening or closing wedge osteotomy to straighten the curved ulna in
      radial clubhands was simulated by using a specially designed computer program.
      Sixty-eight lateral x-ray films of curved ulnas in 39 children aged from a few
      weeks to early adolescence were examined. When lengthening is possible, closing
      wedge osteotomies yield, at best, only millimeters gain in length. Many will
      decrease bone length. There is no advantage in using multiple closing wedges.
      Opening wedges of reasonable angle will lengthen the ulna by 5 mms or more. Some
      multiple opening wedges can produce slightly better gains in length, but no more
      than two wedges should be used.

PMID- 7722253
TI  - The origin and meaning of "neurotization".

PMID- 7722254
TI  - The Founders Lecture: the narrowest hinge of my hand.

PMID- 7722255
TI  - Posterior interosseous nerve paralysis with multiple constrictions.
AB  - We report four cases of posterior interosseous nerve paralysis with multiple
      constrictions. At surgery the constrictions were found between the arcade of
      Frohse and a point of bifurcation of the supinator motor branch. External
      neurolysis with epineurotomy using the microscope was performed in all cases, and
      full recovery was obtained.

PMID- 7722256
TI  - Occupational cumulative trauma.

PMID- 7722257
TI  - Transection of the motor branch of the ulnar nerve as a complication of two
      portal endoscopic carpal tunnel release: a case report.

PMID- 7722258
TI  - Two rapidly growing fatty tumors of the upper limb in children: lipoblastoma and
      infiltrating lipoma.
AB  - One case of lipoblastoma and another case of infiltrating lipoma of the upper
      limb in infancy are reported. These rare benign fatty tumors may be congenital
      and may grow rapidly soon after birth. The classification of these fatty tumors
      and their management are presented to increase awareness of the benign nature of
      these tumors despite their rapid growth and to demonstrate that complete surgical
      excision should be done to prevent local recurrence.

PMID- 7722259
TI  - Leiomyoma of the hand: a case report and review of the literature.

PMID- 7722260
TI  - Anatomy of the extensor tendons of the fingers: variations and multiplicity.
AB  - The extensor tendons to the fingers were dissected in 43 adult hands. The most
      common distribution pattern of the extensor tendons of the fingers was: (1) a
      single extensor indicis proprius (EIP) tendon that inserted ulnar to the extensor
      digitorum communis (EDC) of the index; (2) a single EDC-index; (3) a single EDC
      long; (4) a double EDC-ring; (5) an absent EDC-small; and (5) a double extensor
      digiti quinti (EDQ) with a double insertion. Frequent variations included, a
      double EIP tendon; a double or triple EDC-long tendon; a single or triple EDC
      ring tendon; and a single or double EDC-small tendon. The extensor medii proprius
      was noted in 5 specimens. Increased multiplicity of any tendon was not associated
      with multiplicity of any other tendon, but was associated with a thinner (type 1)
      junctura tendinum between EDC-index and EDC-long. An absent EDC-small was related
      to an increased incidence of a double EDC-ring and the presence of a thick type 3
      junctura tendinum between the EDC-ring and the EDQ or dorsal aponeurosis of the
      small finger. Knowledge of potential tendon multiplicity and variations may help
      in the identification and repair of these structures.

PMID- 7722261
TI  - Extensor digitorum brevis manus associated with a dorsal wrist ganglion: a review
      of five cases.

PMID- 7722262
TI  - Lunate morphology: can it be predicted with routine x-ray films?
AB  - To assess our ability to predict lunate morphology, x-ray films of 81 cadaver
      wrists were obtained. The wrists were then dissected to determine true anatomy,
      specifically the presence or absence of a medial lunate facet. Thirty-five wrists
      were found to be type 1 lunates, while 46 were type 2. Cartilage erosion at the
      proximal pole of the hamate was found in association with 28 of the type 2
      lunates. The accuracy of determining lunate morphology ranged from 64% to 72%.
      Therefore, lunate morphology cannot always be reliably predicted by a standard x
      ray film. Arthrosis at the lunate-hamate articulation is frequent in association
      with type 2 lunates.

PMID- 7722263
TI  - Kienbock's disease in an elderly patient.

PMID- 7722264
TI  - Mini and micro plating of phalangeal and metacarpal fractures: a biomechanical
      study.
AB  - Biomechanical testing was performed in a cadaver model to evaluate the effects of
      plate size and position on fracture stability using Leibinger mini and
      microplates applied on the proximal phalanx and metacarpal. Fresh frozen
      cadaveric metacarpal and proximal phalanges were subjected to a midshaft
      transverse osteotomy followed by application of titanium mini (1.7 mm screw
      diameter) and micro (1.2 mm screw diameter) plates/screws. For the metacarpal, a
      dorsal miniplate, a dorsal microplate, and bilateral microplates were used. For
      the proximal phalanx, similar plate configurations and sizes were used with the
      addition of a unilateral microplate. A three point bending model with both dorsal
      and palmar apex loading was used for all configurations. This study confirms that
      a dorsally applied miniplate provides the greatest rigidity to a dorsal apex
      load.

PMID- 7722265
TI  - Tardy ulnar nerve palsy caused by cubitus varus deformity.
AB  - Fifteen patients with tardy ulnar nerve palsy caused by cubitus varus deformity
      were studied. All patients had a history of previous fracture of the humerus
      during childhood. The mean interval between fracture and onset of symptoms was 15
      years. The severity of the palsy was classified as McGowan's grade I in 12
      patients, grade II in 2 patients, and grade III in 1 patient. The mean carrying
      angle was -2 degrees before surgery. X-ray films showed a shallow ulnar nerve
      groove, a dysplastic humeral trochlea, medial shift of the ulna, and deformity of
      the medial epicondyle. The ulnar nerve was explored in all but one patient.
      Operative findings suggested that the main cause of the palsy was compression by
      a fibrous band running between the two heads of flexor carpi ulnaris. Surgical
      steps included release of the fibrous band in 14 patients with anterior
      subcutaneous transposition of the ulnar nerve in 5 of those patients. A
      corrective osteotomy was done in 11 patients who requested correction of the
      varus deformity. Traumatic cubitus varus deformity should be recognized as
      another cause of cubital tunnel syndrome.

PMID- 7722266
TI  - Wrist arthrodesis for traumatic conditions: a study of plate and local bone graft
      application.
AB  - This study demonstrates the ability to obtain a predictable and complete wrist
      arthrodesis using local bone graft and a dorsal plate. The donor site morbidity
      often seen in using iliac crest graft is eliminated with this method. We examined
      the use of local distal radius bone grafting alone with dorsal plate fixation and
      its ability to provide a predictable fusion. Twenty-eight consecutive patients
      underwent wrist arthrodesis by a standard plate fixation technique. Average
      patient age was 34 years with an average period of symptom duration of 2.1 years.
      The cohort had undergone 17 previous wrist surgical procedures prior to wrist
      arthrodesis. The average followup examination period was 2 years. Grip strength,
      x-ray films, and range of motion were evaluated. All patients had a solid wrist
      arthrodesis at final follow-up examination. Grip strength, pronation/supination,
      and digital motion did not change significantly from the preoperative status. No
      patients complained of wrist pain or instability. Complications included extensor
      tendinitis at the distal aspect of the plate in four patients requiring plate
      removal, carpal tunnel syndrome requiring decompression, and distal radioulnar
      joint pain requiring intra-articular injection of corticosteroid.

PMID- 7722267
TI  - Percutaneous Kirschner wire fixation through the snuff box: an anatomic study.
AB  - We undertook this study to better define the anatomy of the radial aspect of the
      wrist and to establish a zone of safety for the placement of Kirschner wires,
      cannulated screws, and arthroscopes within the anatomic snuff box. Twenty fresh
      frozen cadaver upper extremities underwent placement of three percutaneous
      Kirschner wires under fluoroscopic guidance through the anatomic snuff box. In
      each extremity, one Kirschner wire was placed into the radial styloid, one across
      the scaphocapitate joint, and one across the scapholunate joint. A safe zone of
      mean 0.68 sq cm was found deep to the subcutaneous tissue bordered by the radial
      styloid, the first dorsal compartment, the radial artery, and the superficial
      radial nerve. Kirschner wires placed distal, dorsal, or palmar to the borders of
      the safe zone were at great risk of injuring neurovascular structures. To
      minimize the risk of injury to adjacent structures, we advise a limited incision
      in the safe zone with blunt dissection to the wrist capsule. Though improved
      anatomic understanding, we established a new location for the arthroscopic 1,2
      portal within the snuff box.

PMID- 7722268
TI  - An isolated depressed intraarticular fracture of the olecranon: treatment with
      open reduction and internal fixation.

PMID- 7722269
TI  - Sporotrichosis of the hand: an urban experience.
AB  - Sporotrichosis is uncommon in Canadian urban centers. Lymphocutaneous and fixed
      cutaneous are the most common cutaneous forms of the disease, typically seen in
      the upper extremity in adult patients. History usually reveals a puncture injury
      contaminated with soil. Lesions are refractory to commonly used antibiotics.
      Cultures of biopsy specimens reliably grow the fungus Sporothrix schenkii. First
      line treatment is oral potassium iodide. We have reviewed a series of 7 cases
      from various Toronto teaching hospitals and compared them to the world
      literature.

PMID- 7722270
TI  - Eikenella osteomyelitis in a chronic nail biter: a case report.

PMID- 7722271
TI  - Treatment of recurrent squamous cell carcinoma of the hand in immunosuppressed
      patients.
AB  - Since 1981, 14 patients with kidney transplants have been treated for recurrent
      squamous cell carcinoma of the skin of the dorsum of the hand by total skin
      resection. Frozen sections of the base of the tumor sites were carried out and
      the denuded area was resurfaced with split-skin grafts harvested from non-sun
      exposed areas on the buttock and upper thigh. During follow-up examinations, no
      recurrence was seen in the grafted areas. The appearance was good and hand
      function was satisfactory.

PMID- 7722272
TI  - Comparison of laser Doppler flowmetry and thermometry in the postoperative
      monitoring of replantations.
AB  - Reliable postoperative monitoring in microvascular surgery is necessary to
      improve the success rate of reexplorations following vascular compromise. Surface
      thermometry is known as an easy and inexpensive objective postoperative monitor
      and therefore is used by many microsurgeons. Reliability, however, is not
      satisfactory, and therefore several other instrumental methods have been tested
      of which laser Doppler flowmetry shows the most promising results. This study
      compared laser Doppler flowmetry to thermometry in the postoperative monitoring
      after replantation surgery. In 34 patients, 45 replantations and
      revascularizations were monitored by laser Doppler flowmetry and thermometry. A
      reliable alarm value of 10 PU was defined for replantations and
      revascularizations, with a sensitivity of 93% and a specificity of 94%.
      Thermometry showed a sensitivity of 84% and a specificity of 86% at 29 degrees C.

PMID- 7722274
TI  - An ever increasing knowledge base in support of therapeutic touch.

PMID- 7722273
TI  - Growth factor modulation of the formation of a molded vascularized bone graft in
      vivo.
AB  - Peptide growth factors are potent regulators of osteoblast differentiation,
      proliferation, and maturation. Two of these growth factors, transforming growth
      factor beta (TGF-beta) and basic fibroblast growth factor (bFGF), were used in an
      attempt to stimulate osteoneogenesis and angiogenesis in a molded vascularized
      bone graft in the rat. Custom chambers containing cancellous autograft bone and
      agarose beads and incubated with TGF-beta, bFGF, or a control solution, were
      closed around the femoral artery/vein pedicle for 2-4 weeks. Control grafts were
      completely necrotic and without mechanical integrity. TGF-beta grafts
      demonstrated active osteogenesis around necrotic bone, osteoclastic activity, and
      limited angiogenesis. Basic FGF grafts demonstrated substantial angiogenesis with
      limited osteoblastic activity. This study suggests that TGF-beta and bFGF
      stimulate populations of cells in the formation of a molded vascularized bone
      graft. TGF-beta induces the proliferation and/or activity of osteoblastic cells,
      while bFGF stimulates cells involved in angiogenesis. Despite these findings, an
      insoluble demineralized matrix component may be required for complete
      transformation and graft consolidation.

PMID- 7722275
TI  - Holism in reductionist terms.

PMID- 7722276
TI  - Write right! (matching the manuscript with a journal).

PMID- 7722277
TI  - Santeria.
AB  - The purpose of this ethnographic research was to explore the role of Santeria in
      the orientation of Long Island Cuban-Americans towards health and illness.
      Santeria serves both explanatory and treatment functions. By attributing the
      cause of illness to supernatural forces, Santeria explains why some people stay
      well while others get sick. By dispelling malignant supernatural forces,
      mobilizing beneficial supernatural forces, and decreasing uncertainty and stress,
      Santeria helps to maintain or reinstate balance and a sense of control over one's
      life. An understanding of the role of Santeria in the conceptualization of Long
      Island Cuban-Americans towards health and health care behaviors provides a needed
      link between a people's perception of health and illness and the interventions
      that they find meaningful and acceptable.

PMID- 7722278
TI  - The collision between caring theory and caring practice as a collision between
      feminine and masculine cognitive style.
AB  - In the Swedish education of nurses, teaching should be focused in a way that the
      students develop a holistic view of caring. Swedish health care and medical care
      should be carried out in a way that promotes a holistic view. It seems that the
      education of nurses has prerequisites to develop, and often does present, a
      holistic view to the students, but this view is not always carried over to
      practice. Student nurses think they have a theoretical understanding of a
      holistic view, but they cannot manage to transform their knowledge to practice.
      It is proposed that this failure to transfer knowledge of holistic care
      principles into practice is partly based on the fact that medical and
      technological thought dominate practice in the caring disciplines. This article
      explores some factors influencing caring theory and praxis and possible causes
      for the gap between these areas. The question of gender is proposed as a reason
      for the identified difference between theory and praxis. From a gender
      theoretical perspective, the difference can be understood as a collision between
      feminine and masculine cognitive styles. It is proposed that the caring ideals of
      holism are emphasized by the woman-dominated nursing schools, but these ideals
      are not able to influence practice of the caring professions, which are dominated
      by men.

PMID- 7722279
TI  - A Delphi study of the basic principles and corresponding care goals of holistic
      nursing practice.
AB  - This descriptive, non-experimental study using the Delphi survey process
      identified basic holistic health principles for which holistic nurse
      practitioners agreed guide their healing practice. Seventeen expert holistic
      nurse practitioners (and AHNA leaders) comprised the respondent group. On the
      average these practitioners have been nurses for 25 years and holistic
      practitioners for 11 years. Seventy percent of the group completed all three
      Delphi rounds indicating their agreement regarding 25 principles of holistic
      health, their applicability to practice, and care goals related to each
      principle. A high level of consensus was reached regarding 17 principles. In
      addition to affirming principles related to unity, interdependence, evolution,
      energy fields, and interactions, the AHNA expert nurse practitioners strongly
      emphasized spirituality. The group addressed reality as a unified whole, not
      limited by the material universe, supporting a practice model based on
      holographic perspectives.

PMID- 7722280
TI  - Enthusiasm misplaced? Revisiting cholesterol screening.
AB  - Nursing journals have not reflected the abundant literature criticizing the
      National Cholesterol Education Program's goal to screen every adult American's
      cholesterol levels. Because this goal affects every nurse in professional,
      economic, and personal ways, it behooves nurses to consider the intensive debate
      that frames the benefits claimed for cholesterol screening. Issues raised by the
      debate may give nurses reason to question the program's goals. Once acquainted
      with inherent epidemiologic, methodologic, cost, and public policy issues, nurses
      may conclude there is insufficient scientific evidence to warrant cholesterol
      screening for the entire adult population. Rather, cholesterol screening may best
      be reserved for the relatively few Americans most likely to benefit from both
      screening and subsequent treatment.

PMID- 7722281
TI  - Bandura's self-efficacy theory: a guide for cardiac rehabilitation nursing
      practice.
AB  - To help patients achieve the greatest benefit from cardiac rehabilitation
      programs, nurses must assist them to modify unhealthy behaviors. Many cardiac
      rehabilitation programs, however, lack a theoretical foundation; therefore,
      interventions are usually executed without accounting for the complexities of
      human behavior, and little consideration is given to the difficulties encountered
      in altering unhealthy behavior patterns. Bandura's self-efficacy theory is
      considered a suitable model for cardiac rehabilitation because it provides a
      systematic direction which allows one to interpret, modify, and predict patients'
      behaviors. This article describes the development of and conceptual framework for
      Bandura's theory, how it provides a basis for measurement of self-efficacy, and
      how it may be applied to the study of cardiac rehabilitation. Finally, some
      research issues, which are related to applications of self-efficacy theory in
      cardiac rehabilitation are discussed.

PMID- 7722282
TI  - Older adults' perceptions about wellness.
AB  - This article describes a qualitative investigation regarding the usefulness of
      Pender's health promotion model with community-based, older adults. Specifically,
      the beliefs about wellness of elderly clients seen during a community outreach,
      health promotion project are delineated. The majority of the 33 clients
      interviewed stated they were not well and that their physician kept them informed
      regarding their health status. As part of the nurse-client termination process,
      clients were asked three questions related to themes that emerged during the home
      visits: health status, health care responsibilities, and perception of wellness.
      Findings did not support Pender's health promotion model assumption that
      individuals who engage in health promotion activities perceive their own health
      status positively.

PMID- 7722283
TI  - Regulated expression of Ly-6A.2 is important for T cell development.
AB  - Ly-6A.2 is a surface protein on T cells that may play a role in lymphocyte
      activation. The regulation of Ly-6A.2 expression during T cell lymphopoiesis has
      been intriguing. It is one of the earliest markers expressed on pluripotent
      hemopoietic stem cells and is present on both primitive and mature T cells, but
      its expression is extinguished in the thymus during key developmental stages. To
      determine whether Ly-6A.2 is active on developing T cells, as well as the
      significance of its developmental regulation, Ly-6A.2 was expressed throughout T
      cell development under control of the T cell-specific human CD2 enhancer in
      transgenic mice. The constitutive overexpression of Ly-6A.2 in vivo led to a
      marked impairment in the generation of thymocytes. Development was arrested at
      the time in thymic development when Ly-6A.2 expression is normally turned off.
      These results indicate that the regulated expression of Ly-6A.2 in thymocytes may
      be important for normal development. Moreover, these findings demonstrate that Ly
      6A.2 is active in the thymic microenvironment.

PMID- 7722284
TI  - Analysis of murine soluble Fc epsilon RII sites of cleavage and requirements for
      dual-affinity interaction with IgE.
AB  - The low-affinity receptor for IgE (Fc epsilon RII/CD23) is a type II integral
      membrane protein with an extracellular C-terminal sequence homologous to C-type
      animal lectins. Between this region and the membrane is a repetitive sequence
      predicted to form an alpha-helical coiled-coil and is termed the stalk region.
      The Fc epsilon RII is proteolytically cleaved when at the cell surface in this
      stalk region. Both the 38 Kd and 28 Kd major released fragments were isolated
      from culture media and N-terminal sequencing demonstrated that the cleavage sites
      were in the third and fourth repeat domains, respectively. The identified sites
      show no apparent similarity with the cleavage sites previously identified in
      human Fc epsilon RII. Recent studies have demonstrated that the intact Fc epsilon
      RII interacts with IgE with a dual-affinity, resulting from a multivalent
      interaction with the IgE Fc region; mutant Fc epsilon RII that have a disruption
      of the alpha-helical coiled-coil have a single low-affinity interaction
      consistent with a monomeric interaction with IgE. The soluble Fc epsilon RII were
      shown to interact with IgE with an affinity similar to these mutant Fc epsilon
      RII. Preparation of a chimeric Fc epsilon RII in which the transmembrane and
      cytoplasmic regions were replaced with sequences from Ly-49 revealed that these
      regions played no role in the multimeric association of the Fc epsilon RII
      necessary for dual-affinity interaction with IgE. In addition, a full-sized
      soluble Fc epsilon RII construct was expressed, and this molecule demonstrated
      increased capacity to interact with IgE.

PMID- 7722285
TI  - T cell receptor V alpha 4 is expressed by a subpopulation of V beta 6 T cells
      that respond to the bacterial superantigen staphylococcal enterotoxin B.
AB  - A subpopulation of murine minor lymphocyte-stimulating locus Ag (Mls)-1a
      responsive, TCR V beta 6-expressing T hybrids was responsive to the
      superantigenic bacterial toxin, staphylococcal enterotoxin B (SEB), presented by
      murine MHC class II molecules. Comparative functional and surface marker analyses
      showed that this heterogeneity was not caused by nonspecific effects. It seemed,
      therefore, that the ability of the TCR V beta 6 T hybrids to respond to SEB was
      regulated by non-V beta TCR elements. cDNA sequencing analyses of the TCR beta-
      and alpha-chains expressed by the V beta 6 T hybrids and a beta-chain cDNA gene
      transfer experiment indicated that although J beta, CDR3 beta, J alpha, and CDR3
      alpha were not the relevant elements, SEB responsiveness did correlate with the
      expression of two different members of the V alpha 4 family. A functional
      analysis of a separate panel of V alpha 4 T hybrids expressing different V beta
      elements, including V beta 6, specifically associated SEB responsiveness with the
      V alpha 4, V beta 6 combination. Overall, the data obtained with both panels of T
      hybrids showed SEB responsiveness in five out of five V beta 6, V alpha 4 T
      hybrids, and not in either 11 V beta 6 T hybrids expressing a variety of other V
      alpha elements or four V alpha 4 T hybrids expressing V beta 11, 14, and 15
      elements. Thus, our experiments show for the first time a specific, positive
      qualitative effect of a defined V alpha element on responsiveness to a bacterial
      superantigen. Finally, this study has identified four new V alpha elements.

PMID- 7722286
TI  - IL-10 prevents naturally occurring fetal loss in the CBA x DBA/2 mating
      combination, and local defect in IL-10 production in this abortion-prone
      combination is corrected by in vivo injection of IFN-tau.
AB  - CBA x DBA/2 placentae are quantitatively or qualitatively deficient in their
      production of the anti-inflammatory Th2-type cytokines IL-4 and IL-10 compared
      with the nonresorption-prone CBA x BALB/c mating combination. Wastage in this
      mating combination is accompanied by increased levels of local inflammatory
      cytokines. In addition, alloimmunization enhances the placental production of IL
      4 and IL-10 in CBA x DBA/2 matings. Furthermore, rIL-10 by itself completely
      reverses the high incidence of fetal resorption after i.p. injection. Conversely,
      anti-IL-10 increases the resorption rate, but only in CBA x DBA/2 matings. On the
      other hand, injecting either anti-IFN-gamma or pentoxifillin (an anti-TNF agent)
      partially reduces the resorption. When given together, they produce a synergistic
      remission of fetal loss. Finally, we report that recombinant ovine trophoblast
      protein, an IFN-tau which is known to influence reproductive outcome in
      ruminants, can also counteract increased CBA x DBA/2 fetal resorption. It
      simultaneously induces increased placental IL-4 and IL-10 production in this
      mating combination. These results indicate that the placentally produced anti
      inflammatory cytokines can play a vital role in the survival to term of the fetal
      allograft, by counteracting deleterious inflammatory cytokines.

PMID- 7722287
TI  - Antagonistic interactions among T cell subsets of old mice revealed by limiting
      dilution analysis.
AB  - When CD4 spleen cells from old (but not young) mice are tested for Con A-induced
      proliferation in limiting dilution assays, the dose response curve shows a
      nonlinear relationship. We interpret these observations using a two-cell model,
      in which proliferation of one cell type (LPC1) can be blocked by a second cell
      type (LPC2), which can itself generate detectable proliferation only at high
      multiplicities. The two-cell model accounts for several observations: 1) the
      variation in curve shape as a function of incubation time; 2) the skewed
      distribution of wells scored as "negative" in cultures of old splenocytes; and 3)
      the initially antagonistic effects of old splenocytes titrated into cultures
      containing fixed numbers of young responders. To provide a further test of the
      two-cell model, ionomycin-resistant (CaR) and ionomycin-sensitive (CaS) cells
      were separated using a Percoll/ionomycin gradient. The CaR preparation, shown
      previously to consist largely of memory T cells, showed the dose curve predicted
      for the LPC2 cell type, whereas the CaS (naive) cells showed the single-hit
      kinetics postulated for LPC1 cells. Furthermore, mixtures of CaR and CaS cells
      from young mice reproduced the zigzag dose curve characteristically produced by
      unseparated cells from old mice. These data suggest that the spleens of both
      young and old mice contain two kinds of Con A-responsive CD4 cell: one that
      proliferates vigorously, and a second, calcium ionophore-resistant type that
      proliferates less well, that can interfere with proliferation of the first cell
      type, and whose frequency increases with age.

PMID- 7722288
TI  - Flow cytometric analysis for cytokine production identifies T helper 1, T helper
      2, and T helper 0 cells within the human CD4+CD27- lymphocyte subpopulation.
AB  - Using three-color flow cytometric analysis for the detection of intracellular
      cytokines, we have been able to determine the exact combination of cytokines
      produced by individual T lymphocytes. Because CD4+CD27- lymphocytes have been
      shown to produce more IL-4 and IL-5 than CD4+CD27+ lymphocytes, cells from normal
      individuals (n = 4) and helminth-infected patients (n = 4) were sorted
      magnetically for the CD4+CD27+ and the CD4+CD27- subpopulations. Intracellular
      staining for IL-4, IL-5, and IFN-gamma subsequent to mitogen stimulation for 6 h
      revealed that although almost no CD4+CD27- lymphocytes produce both IL-5 and IFN
      gamma (0.03-1.4%), a distinct proportion produce both IL-4 and IFN-gamma (0.1
      8.0%), and 66% to 84% of IL-5-producing cells also produce IL-4. Patients and
      normal individuals had the same functional T cell subsets, but the CD4+CD27-
      lymphocytes from patients had higher frequencies of cells producing IL-4
      (geometric mean (GM), 24.3% vs 16.4%) or IL-5 (GM, 10.2% vs 2.9%), whereas those
      of normal individuals had higher frequencies of cells producing IFN-gamma (GM,
      44.5% vs 17.2%; p = 0.043). These analyses also revealed that the CD4+CD27-
      population included significantly higher frequencies of cells that were IL-5+IFN
      gamma- (GM, 4.9% vs 1.5%; p = 0.025), IL-4+IFN-gamma- (GM, 13.8% vs 3.5%; p =
      0.025), and IFN-gamma+IL-4-IL-5- (GM, 27.3% vs 12.0%; p = 0.011) than the
      CD4+CD27+ population. Thus, we have clearly demonstrated Th1, Th2, and Th0 cell
      subsets within the CD4+-CD27- population of human lymphocytes.

PMID- 7722289
TI  - Normal adult ramified microglia separated from other central nervous system
      macrophages by flow cytometric sorting. Phenotypic differences defined and direct
      ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells
      compared.
AB  - Ramified microglia in the adult central nervous system (CNS) are the principal
      glial element up-regulating MHC class I and II expression in response to
      inflammatory events or neuronal damage. A proportion of these cells also express
      MHC class II constitutively in the normal CNS. The role of microglia as APCs for
      CD4+ T cells extravasating into the CNS remains undefined. In this study, using
      irradiation bone marrow chimeras in CD45-congenic rats, the phenotype
      CD45lowCD11b/c+ is shown to identify microglial cells specifically within the
      CNS. Highly purified populations of microglia and nonmicroglial but CNS
      associated macrophages (CD45highCD11b/c+) have been obtained directly from the
      adult CNS, by using flow cytometric sorting. Morphologically, freshly isolated
      microglia vs other CNS macrophages are quite distinct. Of the two populations
      recovered from the normal CNS, it is the minority CD45highCD11b/c+ transitional
      macrophage population, and not microglia, that is the effective APC for
      experimental autoimmune encephalomyelitis-inducing CD4+ myelin basic protein
      (MBP)-reactive T cells. CD45highCD11b/c+ CNS macrophages also stimulate MBP
      reactive T cells without addition of MBP to culture, suggesting presentation of
      endogenous Ag. This is the first study in which microglia vs other CNS
      macrophages have been analyzed for APC ability directly from the CNS, with
      substantial cross-contamination between the two populations eliminated. The
      heterogeneity of these populations in terms of APC function is clearly
      demonstrated. Evidence is still lacking that adult CNS microglia have the
      capacity to interact with and stimulate CD4+ T cells to proliferate or secrete IL
      2.

PMID- 7722290
TI  - Mucosal immunization with a bacterial protein antigen genetically coupled to
      cholera toxin A2/B subunits.
AB  - The generation of secretory IgA Abs for specific immune protection of mucosal
      surfaces depends on stimulation of the mucosal immune system, but this is not
      effectively achieved by parenteral or even oral administration of most soluble
      Ags. To harness the exceptional mucosal immunogenicity of cholera toxin (CT),
      which is largely attributed to the cell-binding property of its B subunit, for
      the generation of other oral vaccines, we have genetically replaced the toxic A1
      subunit of CT with a 42-kDa segment of a streptococcal protein adhesin. This
      construct was expressed in Escherichia coli as a chimeric protein that retained
      the GM1 ganglioside-binding activity of CT subunit B and the antigenicity of the
      streptococcal adhesin, as shown by GM1-ELISA developed with Abs to the
      steptococcal segment. The protein composition of chromatographically purified
      chimeric protein was verified by SDS-PAGE and Western blotting with Abs to both
      antigenic components of the construct. Peroral administration of this chimeric
      immunogen in mice elicited high levels of mucosal IgA and serum IgG Abs to the
      streptococcal adhesin, which persisted for at least 6 mo. This strategy allows
      the development of similar constructs from other candidate Ags for oral
      immunization against a variety of mucosally acquired infections.

PMID- 7722291
TI  - Cytotoxic NK1.1 Ag+ alpha beta T cells with intermediate TCR induced in the liver
      of mice by IL-12.
AB  - Systemic administration of IL-12 greatly reduced the hepatic metastases of i.v.
      injected liver metastatic EL4 tumor cells in C57BL/6 +/+ and nu/nu mice.
      Cytotoxic assay in vitro revealed that administration of IL-12 greatly enhanced
      cytotoxicity of hepatic mononuclear cells (MNC) against various NK- sensitive and
      -resistant tumor targets, including EL4 cells, whereas only slight or moderate
      augmentation of the cytotoxicity was observed in splenocytes in normal and nude
      mice. After IL-12 administration, hepatic MNC increased in number and showed
      vigorous proliferation in vitro. Hepatic MNC of control C57BL/6 +/+ mice contain
      alpha beta T cells with intermediate TCR (TCRint) as well as alpha beta T cells
      with bright TCR, whereas hepatic MNC of nu/nu mice have only TCRint cells. These
      TCRint cells are found to be NK1.1 Ag+ (NK1+ TCRint). Systemic administration of
      IL-12 into normal and nude mice markedly augments the NK1 expression of NK1+
      TCRint cells (NK1high TCRint), which is comparable to or brighter than that of NK
      cells in the liver, whereas alpha beta T cells with bright TCR or gamma delta T
      cells in the liver are NK1-. Depletion of either NK1.1+ or CD3+ cells, but not
      CD8+ cells, of hepatic MNC from IL-12-treated normal mice by respective Abs and C
      in vitro abrogate their cytotoxicity. These results revealed that TCRint cells
      are potent cytotoxic effector cells and suggest that NK1high TCRint cells are the
      main antimetastatic population in the liver, and that TCRint cells are
      functionally different from regular T cells with bright TCR.

PMID- 7722292
TI  - The role of IL-10 in human B cell activation, proliferation, and differentiation.
AB  - Recent studies have disclosed variable effects of IL-10 on viabilities of human B
      lineage cells. Thus, IL-10 has been shown to prevent apoptosis of germinal center
      B cells, whereas IL-10 has been found to induce apoptosis of B-chronic
      lymphocytic leukemia cells, suggesting the possibility that the effects of IL-10
      might be different depending on the state of activation of B cells. The current
      studies therefore examined in detail the regulation of the survival of human
      peripheral blood B cells by IL-10 and its relevance to Ig production. Highly
      purified B cells from healthy adult individuals were cultured with Staphylococcus
      aureus (SA) Cowan I in the presence or absence of IL-10. When IL-10 was present
      during the initial activation of B cells with SA, IL-10 facilitated the apoptosis
      of SA-activated B cells, as determined by staining with propidium iodide,
      followed by analysis with flow cytometry, thus resulting in very modest IgM
      production. IL-2 prevented the IL-10-mediated progression of the apoptosis of SA
      activated B cells during the initial activation, and thus restored the further
      differentiation of these B cells into Ig secreting cells. By contrast, IL-10
      rather rescued SA-activated B cells from apoptosis and thus supported the
      differentiation of these B cells without any influences of IL-2, when it was
      added after 72 h of culture. Of note, cyclosporin A prevented the IL-10-mediated
      promotion of the apoptosis of SA-activated B cells, thus resulting in the marked
      enhancement of IgM production of B cells stimulated with SA + IL-10. Finally, the
      promotion or prevention of the IL-10-mediated apoptosis was correlated with the
      expression of Bcl-2 oncoprotein in SA-activated B cells. These results indicate
      that the effects of IL-10 are different depending on the state of activation of B
      cells after ligation of Ag receptors. Thus, the data have demonstrated that IL-10
      during the initial activation delivers negative signals that promote the
      apoptosis of B cells, whereas IL-10 supports the differentiation of B cells in
      the complete absence of IL-2 during the subsequent responses following
      activation. These results therefore emphasize unique biphasic effects of IL-10 on
      human B cell responsiveness in determining the outcome of humoral immune
      responses.

PMID- 7722293
TI  - Differential requirement for protein tyrosine kinase Fyn in the functional
      activation of antigen-specific T lymphocyte clones through the TCR or Thy-1.
AB  - The protein tyrosine kinase Fyn has been shown to be involved in signal
      transduction through the TCR and the glycosyl-phosphatidylinositol-linked surface
      molecule Thy-1 expressed on T cells. In this study, we examine the requirement
      for Fyn expression in signaling through the TCR or Thy-1 using a panel of Ag
      specific T cell clones derived from fyn-/- mutant mice. These clones do not
      express normal Fyn protein, as measured by immune-complex kinase reaction using
      anti-Fyn Ab. Stimulation through the TCR, either by APC bearing relevant Ag or by
      immobilized anti-CD3 mAb, resulted in comparable levels of proliferation,
      lymphokine production, and cytolysis by clones from both wild-type and fyn-/-
      mice. In contrast, stimulation through Thy-1, using soluble (or cross-linked)
      anti-Thy-1 mAb, was deficient, as measured by these responses. Thus, Fyn
      expression is selectively required for functional activation through Thy-1 in
      these T cell clones.

PMID- 7722294
TI  - In situ detection and characterization of apoptotic thymocytes in human thymus.
      Expression of bcl-2 in vivo does not prevent apoptosis.
AB  - Apoptosis plays a crucial role in shaping the T cell repertoire during T cell
      development in the thymus. The observed disappearance in the thymus of CD4+ CD8+
      thymocytes with a specific TCR, and the lack of CD4+ or CD8+ single positive
      mature cells expressing the same TCR specificity in the periphery have led to the
      conclusion that deletion occurs at the CD4+ CD8+ double positive stage; however,
      there is no direct evidence demonstrating apoptotic CD4+ CD8+ cells in situ.
      Apoptosis of thymocytes in situ at other stages of T cell development has also
      not been reported. Using three-color immunofluorescence and flow cytometric
      assays on frozen human thymic tissue and freshly isolated human thymocytes
      respectively, we directly identify CD4+ CD8+ and CD4- CD8- thymocytes in newborn
      human thymus that contain intracellular fragmented DNA and are therefore
      apoptotic. We determine that 75% of the apoptotic thymocytes are CD4+ CD8+ double
      positive apoptotic thymocytes, and interestingly, that 13% are CD4- CD8- double
      negative thymocytes. The majority of apoptotic thymocytes in situ are detected at
      the cortical-medullary junction; however, apoptotic thymocytes are also found
      scattered throughout the cortex. Furthermore, we determine that within the
      apoptotic thymocyte population, 54% express the apoptotic regulatory protein bcl
      2 in vivo, whereas 32% are bcl-2 negative. Thus, our in vivo data directly
      demonstrate that both CD4+ CD8+ and CD4- CD8- human thymocytes die in situ via an
      apoptotic process, and that expression of the bcl-2 protein in situ does not
      prevent immature thymocytes from apoptosis.

PMID- 7722295
TI  - T cell gelatinases mediate basement membrane transmigration in vitro.
AB  - T cell homing into extravascular sites requires penetration across the
      subendothelial basal lamina, a specialized nonfibrillar connective tissue
      structure that anchors endothelial cells to parenchymal surfaces. Herein, we show
      that normal human T cells express gelatinases A and B, two matrix
      metalloproteinases active against the major basal lamina constituents, collagen
      types IV and V. Expression is confirmed at both the mRNA and protein levels.
      Gelatinase B is expressed constitutively, whereas gelatinases A and B expression
      is induced by T cell activation. In vitro migration of resting T cells across a
      basal lamina equivalent is mediated by gelatinase B, because it is specifically
      blocked by GM6001, a hydroxamic acid inhibitor of matrix metalloproteinases.
      Inhibition of T cell homing by interference with gelatinase function may
      represent a useful approach to the treatment of T cell-mediated autoimmune
      diseases.

PMID- 7722296
TI  - Gamma delta T cells down-regulate primary IgE responses in rats to inhaled
      soluble protein antigens.
AB  - The biologic role and repertoire of cells bearing the gamma delta T cell receptor
      has not been fully defined. However, their tropism for epithelial
      microenvironments is recognized and suggests an important role for these cells in
      immune defense at mucosal tissue surfaces. The study presented below utilizes an
      experimental model in which repeated exposure of Brown Norway rats to OVA by
      inhalation induces a state of Ag-specific, IgE isotype-specific "tolerance" via
      immune deviation. This process seems similar to oral tolerance in the gut. This
      form of tolerance was adoptively transferred to naive syngeneic recipients by
      i.p. injection of as few as 10(3) positively selected TCR-gamma delta+ cells from
      OVA-exposed rats. These TCR-gamma delta+ T-cells are demonstrated to produce high
      levels of INF-gamma in response to OVA stimulation, and this provides a potential
      mechanism for the inhibition of Th2 cell proliferation, resulting in suppression
      of IgE production. The unique potency of these cells in selective suppression of
      IgE Ab production in response to natural "mucosal" Ag exposure suggests a
      potentially important role in protection against primary allergic sensitization
      in vivo.

PMID- 7722297
TI  - Engagement of the antigen-receptor on immature murine B lymphocytes results in
      death by apoptosis.
AB  - During their development B lymphocytes pass through a maturational stage in which
      encounter with Ag leads to tolerance rather than activation. At least four
      mechanisms for achieving B cell tolerance have been reported: deletion, anergy,
      receptor editing, and competition for follicular niches. Although turnover rates
      for immature B cells in the adult mouse bone marrow and several transgenic model
      systems suggest that a major process contributing to negative selection of B
      cells is deletion, a detailed study of the negative effect of Ag-receptor
      engagement on primary, immature B cell survival has never been undertaken. We
      have utilized an in vitro culture system to determine whether cross-linking sIgM
      on tolerance-susceptible sIgM+IgD- B cells results in deletion by apoptosis. In
      contrast to the effect of sIgM cross-linking on mature splenic B cells, treatment
      of immature, bone marrow-derived B cells results in significant levels of
      apoptotic death. Ag receptor-mediated apoptosis is detectable by 14 h after sIgM
      engagement. Moreover, IL-4 and cycloheximide, which have previously been shown to
      prevent B cell tolerance induction, specifically block the sIgM-induced apoptosis
      observed in the immature B cells. Similarly, immature B cells from the neonatal
      spleen are also susceptible to apoptosis after sIgM cross-linking, although they
      manifest somewhat higher levels of unstimulated apoptosis as compared with bone
      marrow-derived B cells. These studies are the first detailed demonstration of Ag
      receptor-mediated apoptosis of primary immature stage B lymphocytes.

PMID- 7722299
TI  - V7, a novel leukocyte surface protein that participates in T cell activation. I.
      Tissue distribution and functional studies.
AB  - Among a panel of mouse mAbs generated to a human T cell clone, one mAb, V7.1,
      inhibited T cell activation in the mixed lymphocyte reaction and was studied
      further. V7.1 reacted strongly with Ag-specific T cell clones, in addition to
      freshly isolated monocytes and granulocytes. However, the mAb reacted weakly with
      freshly isolated PBLs (T cells, B cells, and NK cells), T cells stimulated with
      phytohemagglutinin, or Con A, and did not stain the vast majority of transformed
      cell lines of hemopoietic origin. Stimulation of T cells with anti-CD3, or the
      combination of anti-CD3 and PMA, or anti-CD3, PMA and ionomycin, markedly
      increased V7.1 surface staining. The mAb precipitated a single polypeptide chain
      of approximately 135 kDa from alloactivated T cells or monocytes, which was
      reduced to approximately 110 kDa after treatment with N-glycanase. The
      proliferative response of T cells to allogeneic monocytes or B lymphoblastoid
      cells was inhibited by V7.1, and inhibition was maximal when the mAb was present
      at the initiation of culture. V7.1 also exhibited dose-dependent inhibition of
      the T cell response to immobilized anti-CD3 Ab in the absence of APCs, indicating
      that the inhibitory effect of this Ab occurs at the T cell level. Expression of
      CD25 (IL-2R) on anti-CD3-activated T cells and secretion of IL-2 induced with
      anti-CD3 and PMA were inhibited by V7.1, whereas the Ab had no effect on T cell
      proliferation induced by PHA or Con A or on T cell-mediated cytotoxicity. These
      results indicate that V7.1 recognizes a novel leukocyte surface glycoprotein,
      designated V7, that is up-regulated on Ag but not lectin-activated T cells, and
      appears to play a role in TCR/CD3-dependent T cell activation. In an accompanying
      study, the gene encoding the V7 Ag is described and the molecule is shown to be a
      novel member of the Ig superfamily.

PMID- 7722300
TI  - V7, a novel leukocyte surface protein that participates in T cell activation. II.
      Molecular cloning and characterization of the V7 gene.
AB  - V7 is a cell surface glycoprotein expressed on Ag-activated T cells, monocytes,
      and granulocytes, as well as subpopulations of T cells and accessory cells
      present in thymic medulla and tonsil. A mAb directed against V7 inhibits the
      proliferative response of T cells to allogeneic cells or immobilized anti-CD3 Ab,
      but not lectin mitogens, suggesting that V7 plays a role in TCR/CD3-mediated T
      cell activation. We have used the anti-V7 Ab in eukaryotic expression cloning
      experiments to isolate a cDNA clone containing a 3,340-bp insert that encodes V7
      when transiently expressed in simian and murine fibroblastoid cells. DNA sequence
      analysis revealed a novel 1,021-amino acid open reading frame the structure of
      which conforms to the category of type I integral membrane proteins. The protein
      sequence includes a 20-residue putative hydrophobic signal sequence followed by a
      putative extracellular domain of 934 amino acids, a prototypic hydrophobic
      transmembrane spanning a domain of 25 residues, and finally a short and highly
      charged putative cytoplasmic domain of 42 residues. The extracellular domain
      contains seven pairs of regularly spaced cysteine residues, suggestive of Ig-like
      domains. On the basis of statistical analysis of the sequences of the putative
      cysteine loops, all seven of the Ig-like domains belong to the variable, or V
      type, category. By using fluorescence in situ hybridization, we have mapped the
      V7 gene to human chromosome Ip13. Thus, the V7 glycoprotein represents a novel
      member of the Ig superfamily that is involved in critical intracellular signals
      essential for immune function.

PMID- 7722298
TI  - Antigen processing in vivo and the elicitation of primary CTL responses.
AB  - CD8+ T lymphocytes (TCD8+) play an important role in cellular immune responses.
      TCD8+ recognize MHC class I molecules complexed to peptides of 8 to 10 residues
      derived largely from cytosolic proteins. Proteins are generally thought to be
      fragmented in the cytoplasm and delivered to nascent class I molecules in the
      endoplasmic reticulum (ER) by a peptide transporter encoded by the MHC. To
      explore the extent to which TCD8+ induction in vivo is limited by proteolysis or
      peptide transport into the ER, mice were immunized with recombinant vaccinia
      viruses containing mini-genes encoding antigenic peptides (bypassing the need for
      proteolysis), or these peptides with a NH2-terminal ER insertion sequence
      (bypassing the requirements for both proteolysis and transport). Additionally,
      mice were immunized with recombinant vaccinia viruses encoding rapidly degraded
      fragments of proteins. We report that limitations in induction of TCD8+ responses
      vary among Ags: for some, full length proteins are as immunogenic as other forms
      tested; for others, maximal responses are induced by peptides or by peptides
      targeted to the ER. Most importantly, in every circumstance examined, targeting
      peptides to the ER never diminished, and in some cases greatly enhanced, the
      TCD8+ immune response and provide an important alternative strategy in the design
      of live viral or naked DNA vaccines for the treatment of cancer and infectious
      diseases.

PMID- 7722301
TI  - B cell selection and allelic exclusion of an anti-DNA Ig transgene in MRL-lpr/lpr
      mice.
AB  - We have used an Ig transgene (VH3H9) that increases the frequency of anti-DNA
      autoantibodies to address whether the production of antinuclear Abs in systemic
      lupus erythematosus is the consequence of a breakdown of B cell tolerance. We
      have shown that nonautoimmune mice regulate anti-DNA B cells, and that lupus
      prone MRL-lpr/lpr mice are defective in this regulation. Here we show that a
      subset of anti-DNA B cells, namely those that stain nuclei in a homogeneous
      fashion, not only fail to be deleted in MRL-lpr/lpr mice, but undergo
      preferential clonal expansion. In addition, we describe a surprising finding: the
      VH3H9 transgene is less efficient at inhibiting endogenous heavy chain gene
      rearrangement on the autoimmune-prone MRL-lpr/lpr genetic background than on the
      nonautoimmune BALB/c background.

PMID- 7722302
TI  - Differential expression of endoglin on fetal and adult hematopoietic cells in
      human bone marrow.
AB  - Endoglin, a glycoprotein that is expressed by human endothelial cells, binds TGF
      beta 1 and -beta 3 with high affinity. It was originally identified with the 44G4
      mAb that was produced against a human pre-B cell line. We now report that another
      anti-pre-B cell mAb, 29-G8, reacts with pro-B and pre-B leukemic cells, but not
      with mature B and T cells, and recognizes a different epitope of endoglin. The 29
      G8 mAb bound specifically to recombinant endoglin and immunoprecipitated a
      phosphorylated homodimeric glycoprotein with subunits of M(r) 95,000 from the 697
      pre-B cell line. This new Ab removed all of the molecules identified by the
      prototypic 44G4 anti-endoglin Ab, but the reverse was not true. A subpopulation
      of 29-G8+ endoglin molecules on this pre-B cell line was unreactive with the 44G4
      mAb, thus suggesting that these anti-endoglin Abs see different epitopes that may
      discriminate different species of endoglin molecules. Flow cytometric analysis
      with the 29-G8 mAb revealed two endoglin-positive subpopulations in fetal bone
      marrow: early B-lineage precursor cells (CD19+ and CD34+), and proerythroblasts
      (CD71+ and glycophorin A+). In adult bone marrow, only the proerythroblast
      subpopulation was observed. Stromal cells derived from fetal bone marrow also
      reacted strongly with the 29-G8 and 44G4 Abs, and these cells responded with
      enhanced proliferation after stimulation with either TGF-beta 1 or the anti
      endoglin Abs. Thus, endoglin, a specialized component of the TGF-beta receptor
      system, may play a physiologic role in the stromal-hemopoietic cell interactions
      occurring during development.

PMID- 7722303
TI  - Constitutive endocytosis and degradation of CD22 by human B cells.
AB  - The CD22 B lymphocyte-surface Ag is an important component of the B cell-surface
      IgM (sIgM)/B cell receptor complex and has been shown to regulate B cell
      activation. In addition, this molecule has been shown to be an effective target
      for immunotherapy of B cell malignancies using immunotoxins and
      radioimmunoconjugates. In this report we describe the internalization and
      metabolic degradation of this molecule under constitutive conditions and after
      stimulation of B cells with phorbol dibutyrate or mAbs binding to sIgM, CD19, and
      CD22. Flow cytometry, "neuraminidase protection," and "neuraminidase shift"
      assays demonstrated that CD22 is internalized constitutively by unstimulated B
      cell lines and subsequently degraded in an acidic intracellular compartment
      (presumably lysosomes) without detectable recycling of the molecule back to the
      cell surface. Ligation of CD22 with anti-CD22 mAbs markedly increased CD22
      internalization but did not affect the rate of intracellular degradation of CD22,
      suggesting that anti-CD22 mAbs perturb the intracellular trafficking of CD22. In
      contrast, CD22 internalization and degradation was unaffected by stimulation of B
      cell lines with phorbol dibutyrate or ligation of other components of the B cell
      receptor complex (e.g. CD19, sIgM) with mAbs. These patterns of internalization
      and degradation under constitutive and stimulated conditions contrast with those
      reported for other lymphoid differentiation Ags (e.g., the TCR, CD3, CD4, and the
      transferrin receptor), and may help explain the utility of this molecule as a
      target for immunoconjugate therapy.

PMID- 7722304
TI  - Regulatory role of gamma delta T cells in uterine intraepithelial lymphocytes in
      maternal antifetal immune response.
AB  - To elucidate the potential roles of the gamma delta T cells in uterine
      intraepithelial lymphocytes (IEL) in the regulation of maternal antifetal immune
      response during pregnancy, we examined the kinetics and function of gamma delta T
      cells in uterine IEL obtained from (C3H/He x AKR/J) pregnancy. The number of
      gamma delta T cells increased in the uterine IEL in (C3H/HexAKR/J) pregnancy more
      than those in (C3H/HexC3H/He) pregnancy and much more than in nonpregnant C3H/He
      mice. The uterine IEL in (C3H/HexC3H/He) pregnancy significantly proliferated in
      response to AKR/J stimulator cells. In contrast, the uterine IEL in
      (C3H/HexAKR/J) pregnancy showed little, if any, proliferation in response to the
      same stimulator cells. gamma delta T cell depletion from the uterine IEL in
      (C3H/HexAKR/J) pregnancy restored their responsiveness against AKR/J stimulator
      cells. Both gamma delta T cell-enriched fraction and alpha beta T cell-depleted
      fraction, but neither gamma delta T cell-depleted fraction nor alpha beta T cell
      enriched fraction in the uterine IEL exhibited suppressive activity against
      allogeneic responses of nonpregnant C3H/He LN cells. This suppressive activity
      was shown by transferring the supernatant of culture medium in the uterine IEL
      stimulated with AKR/J cells that contained a large amount of TGF-beta, and the
      suppressive activity was significantly blocked by addition of anti-TGF-beta mAb
      to the culture. Taken together, our results suggest that gamma delta T cells in
      the uterine IEL suppress the maternal antifetal immune response at the maternal
      fetal interface at least in part through TGF-beta production to prevent a
      rejection of the fetus.

PMID- 7722305
TI  - Identification and analysis of the expression of CD8 alpha beta and CD8 alpha
      alpha isoforms in chickens reveals a major TCR-gamma delta CD8 alpha beta subset
      of intestinal intraepithelial lymphocytes.
AB  - Expression screening has been used to clone cDNAs encoding the alpha- and beta
      chains of chicken CD8. Amino acid sequence similarities with the mammalian
      sequences were about 30%. Many amino acid residues of structural or functional
      importance were more highly conserved, as were the overall structures of both
      chains. Like human CD8 alpha, the chicken alpha-chain lacked sites for N-linked
      glycosylation, but the beta-chain contained three such sites. In COS cells
      transfected with CD8 beta cDNA, surface expression of the beta-chain was
      dependent on co-transfection of the alpha-chain cDNA, indicating that, as in
      mammals, chicken CD8 can be expressed as a CD8 alpha alpha homodimer or as a CD8
      alpha beta heterodimer. Immunofluorescence analysis with mAbs that were shown to
      identify the CD8 alpha- and CD8 beta-chains revealed that the vast majority of
      the CD8+ cells in the thymus, spleen, and blood of adult chickens express both
      CD8 alpha- and CD8 beta-chains. However, a relatively large proportion of the
      CD8+ TCR-gamma delta cells in the spleens of embryos and young chicks express
      only the alpha-chain of CD8. Among intestinal epithelial lymphocytes the major
      CD8+ T cell populations present in mice are conserved, but there is a population
      of TCR-gamma delta CD8 alpha beta cells that is not found in rodents. This
      observation is important in interpretation of experiments examining the pathways
      of development of intestinal intraepithelial lymphocytes in chickens.

PMID- 7722306
TI  - IL-4 activates a latent DNA-binding factor that binds a shared IFN-gamma and IL-4
      response element present in the germ-line gamma 1 Ig promoter.
AB  - IL-4 regulates transcription of the germ-line gamma 1 Ig gene in murine B cells
      and by doing so targets this isotype for switch recombination by an unknown
      mechanism. In this study, we have identified an IL-4-induced DNA-binding protein
      factor in murine B cells designated NF-IL-4-gamma 1. This factor binds
      specifically to a site within a 13-bp DNA sequence extending from -125 to -113
      (5' CATTCACATGAAG 3') in the germ-line gamma 1 promoter and shown previously to
      be important for IL-4-responsive transcription. This sequence is highly
      homologous to the IFN-gamma activation site or GAS, and competitive binding
      studies demonstrate that NF-IL-4-gamma 1 can also bind to GAS elements in the
      promoters of two IFN-gamma-responsive genes and to an IL-4-responsive element in
      the germ-line epsilon Ig promoter. NF-IL-4-gamma 1 is rapidly induced in the
      absence of de novo protein synthesis and expression is sustained through day 4 of
      in vitro culture with IL-4 and LPS. Induction of NF-IL-4-gamma 1 is inhibited by
      the kinase inhibitor staurosporine and the factor itself requires phosphorylation
      for binding activity. The binding specificity and expression characteristics of
      NF-IL-4-gamma 1 suggest identity with other recently described IL-4-activated,
      GAS-binding factors that are members of the signal transducers and activators of
      transcription (STAT) family of cytokine-responsive transcription factors.

PMID- 7722307
TI  - Heavy chain variable region, light chain variable region, and heavy chain CDR3
      influences on the mono- and polyreactivity and on the affinity of human
      monoclonal rheumatoid factors.
AB  - Monoreactive high affinity pathologic autoantibodies were supposed previously to
      derive through somatic mutation from polyreactive low affinity autoantibodies
      that are encoded by a small set of unmutated V region genes in fetal and neonatal
      B cells. However, recent data exploring the physiologically expressed Ab
      repertoire and the importance of the stochastically generated heavy chain CDR3 (H
      CDR3) in autoreactivity suggest that this scheme is incomplete. Here we analyzed
      via gene-swapping experiments and site-directed mutagenesis the relative
      contributions of the mutations in the light chain variable region (VL) and the
      heavy chain variable region (VH) domains and of the H-CDR3 in the autoreactivity
      of two IgM rheumatoid factors (RF), one a polyreactive low affinity Ab, the other
      a monoreactive high affinity Ab. These two RFs derived from the same V kappa III
      (humkv325) and VH1 (51p1) genes, but differed from each other by a few mutations
      and by the structure of the H-CDR3. The analysis of the reactivity patterns of
      different combinations of wild-type and in vitro engineered hybrid gene products
      clearly demonstrates the main influence of the H-CDR3 in the autoAb activity
      profiles. The results directly demonstrate the previously proposed hypothesis,
      namely, that the H-CDR3 plays a critical role in distinguishing poly- from
      monospecific RF. However, the data also indicate that self polyreactivity is a
      very fragile property and is dependent upon the primary structure of the VH
      segment.

PMID- 7722308
TI  - A novel octamer regulatory element in the VH11 leader exon of B-1 cells.
AB  - B-1 cells (CD5 B cells) represent an initial fetal wave of B cell lymphopoiesis.
      B-1 cells have fundamental properties that are unique from conventional B cells,
      including a restricted Ab repertoire. We investigated the mechanism for the
      overrepresentation of one such Ig H chain variable-region gene, VH11, by murine B
      1 cells. We postulated that a cis-regulatory element contributed to the use of
      VH11. We observed that the DNA encoding the leader peptide of VH11 was atypically
      A/T rich and thus was a candidate for nuclear protein binding. By electrophoretic
      mobility shift analysis, we found that the VH11 leader DNA specifically bound to
      three protein complexes present in the nucleus of the B-1 cell line AJ9. Of these
      bands, one was ubiquitous for all cells examined (lymphoid and nonlymphoid);
      another band was present only in B cells, and the third band was specific for B-1
      cells that expressed VH11 or VH12. In addition to its binding properties, the
      VH11 leader sequence also displayed modest tissue-specific enhancer activity. By
      DNA footprint analysis, all three protein complexes were found to bind to an
      octamer motif embedded within the VH11 leader DNA. To identify the octamer
      binding proteins, a panel of octamer-specific Abs was used. We found that the
      ubiquitous band was Oct-1, and the B cell-specific band was Oct-2. The B-1 cell
      specific nuclear binding protein was neither Oct-1 nor Oct-2, but may be a novel
      POU domain protein. We hypothesize that the VH11 leader octamer site may target
      this gene for preferential rearrangement and/or expression and therefore would be
      a contributing factor in the increased use of this gene by B-1 cells.

PMID- 7722309
TI  - Peptides control the gain and loss of allele specificity by mutated MHC class I
      molecules.
AB  - To analyze the molecular basis of MHC class I allele-restricted peptide
      recognition, a set of eight Ld/Lq mutants was constructed and tested for peptide
      recognition by allele-restricted and peptide-specific CTL. The MHC molecules H
      2Ld and H-2Lq differ at six amino acid positions (95, 97, 107, 116, 155, 157)
      located within the alpha 2 domain of the molecule. Both molecules present the
      lymphocytic choriomeningitis virus (LCMV) nucleoprotein-derived peptide RPQASGVYM
      and the murine cytomegalovirus (MCMV) pp89-derived peptide YPHFMPTNL to the
      respective virus-specific CD8+ CTL is a strictly allele-restricted fashion. All
      mutated MHC class I molecules did still bind the LCMV peptide and seven of eight
      mutants retained MCMV peptide binding. The exchange Arg-->Trp at position 97 of
      Lq in pocket C of the peptide binding groove prevented binding of the MCMV ligand
      and this loss was compensated by the additional exchange of Ile-->Leu in position
      95 (pocket F). Within the Lq molecule, single mutations at either position 97 on
      the floor of the groove or position 155 of the wall sufficed for a gain of LCMV
      peptide recognition by Ld-restricted CTL. Altogether, six of eight mutants
      resulted in a gain of recognition by CTL specific for the other allele. Thus, six
      of the eight mutants lost MHC-restricted recognition and were accepted by both Ld
      as well as Lq-restricted CTL when presenting the LCMV peptide. Only one case of
      simultaneous recognition of the MCMV peptide by both Ld- as well as Lq-restricted
      CTL was noted. In other mutations, a gain of recognition by Ld-restricted CTL was
      associated with a loss of recognition of Lq-restricted CTL. Analysis of extracted
      MCMV peptide from mutant molecules excluded quantitative differences in presented
      MCMV peptide as a reason for the lack of CTL recognition. Altogether, the results
      show that, rather than aminoacids at certain residue positions, individual
      peptides govern MHC allele specificity of CTL recognition.

PMID- 7722310
TI  - Identification of porcine endothelial cell membrane antigens recognized by human
      xenoreactive natural antibodies.
AB  - Rejection of an organ transplanted into a phylogenetically disparate recipient
      may be initiated by the binding of xenoreactive natural Abs of the recipient to
      Ags expressed on donor endothelium leading to the activation of the C system.
      Having previously shown that human xenoreactive Abs bind predominantly to N
      linked oligosaccharides on porcine endothelial cell glycoproteins, we sought to
      identify those glycoproteins to gain insight into the pathogenesis of the
      rejection reaction and to develop improved methods for depleting those Abs. Based
      on amino-terminal and internal sequencing of the glycoproteins, reactivity with
      monospecific rabbit Abs, and functional properties, the porcine endothelial cell
      targets of human natural Abs were shown to be the von Willebrand factor, integrin
      alpha 1, alpha v, alpha 3/alpha 5, beta 1, and beta 3 chains and a 95-kDa
      glycoprotein homologous with chick DM-GRASP. Human and baboon Abs directed
      against those glycoproteins were shown to be absorbed during perfusion of porcine
      organs and the binding of human IgM to the isolated glycoproteins to initiate the
      activation of C leading to formation of iC3b neoantigen. The determinants
      recognized by human xenoreactive Abs had immunodominant alpha-galactosyl residues
      based on affinity chromatography, reactivity with anti-Gal alpha(1-3)Gal Abs and
      sensitivity to alpha-galactosidase. The findings show that members of the
      integrin family and the von Willebrand factor are major targets of xenoreactive
      Abs and suggest potential mechanisms by which the binding of Abs to endothelial
      cells might perturb the physiology of those cells and thus cause aberrant
      functioning of a tissue or organ.

PMID- 7722311
TI  - Rearrangement and expression of the human psi C lambda 6 gene segment results in
      a surface Ig receptor with a truncated light chain constant region.
AB  - The constant region of the human Ig lambda locus consists of seven tandemly
      organized J-C gene segments. Although it has been established that the J-C lambda
      1, J-C lambda 2, J-C lambda 3, and J-C lambda 7 gene segments are functional, and
      code for the four distinct Ig lambda isotypes found in human serum, the J-C
      lambda 4, J-C lambda 5, and J-C lambda 6 gene segments are generally considered
      to be pseudogenes. Although one example of a functional J-C lambda 6 gene segment
      has been documented, in the majority of cases, J-C lambda 6 is rendered
      nonfunctional by virtue of a single duplication of four nucleotides, creating a
      premature translational arrest. We show here that rearrangements to the J-C
      lambda 6 gene segment do occur, and that such a rearrangement encodes an Ig
      lambda protein that lacks the terminal end of the constant region. We also show
      that this truncated protein is expressed on the surface with the IgH chain,
      creating an unusual surface Ig (sIg) receptor (sIg delta CL). Cells that express
      this receptor on the surface do so at significantly reduced levels compared with
      clonally related variants, which express sIg receptors with conventional Ig
      lambda L chains. However, the effects of sIg cross-linking on tyrosine
      phosphorylation and surface expression of the CD25 and CD71 Ags are similar in
      cells that express conventional sIg receptors and in those that express sIg delta
      CL receptors, suggesting that the latter could possibly function as an Ag
      receptor.

PMID- 7722312
TI  - Characterization of the constitutive and inducible components of a T cell IL-4
      activation responsive element.
AB  - An Il-4 regulatory element, activation responsive element (ARE), located between 
      88 and -60, contributes to activation-dependent transcription of IL-4/CAT
      reporter gene constructs in T cells. It was previously demonstrated that nuclear
      proteins present in both unstimulated and stimulated T cells specifically
      interact with the ARE. In this study, these proteins were further characterized.
      UV cross-linking experiments established that multiple proteins are associated
      with the ARE in both the constitutive and activation-dependent complexes and
      several of these have identical apparent m.w. The formation of both complexes is
      dependent on the same ARE subsequence. In addition, activator protein 1 family
      members are uniquely associated with the activation-dependent complex. These
      results support a model in which activation-dependent proteins, including jun/fos
      family members, associate with a preexisting transcription complex to influence
      inducible IL-4 gene transcription. The ARE shares 9 bp of sequence identity with
      the IL-2 nuclear factor of activated T cell (NF-AT) binding site within the
      critical protein binding region, and several features of ARE-protein interactions
      are similar to the NF-AT transcription complex. However, we demonstrate that the
      constitutive nuclear ARE-associated factors react with Abs, raised to NF-ATp and
      NF-ATc, preferentially bind to the ARE but not to the NF-AT binding site and are
      cyclosporin A sensitive. Taken together, these data indicate that there are IL-4
      gene-specific factors associated with the ARE and that the formation of the ARE
      and NF-AT complexes are regulated differently.

PMID- 7722313
TI  - Rat mammary adenocarcinoma 13762 expressing IFN-gamma elicits antitumor CD4+ MHC
      class II-restricted T cells that are cytolytic in vitro and tumoricidal in vivo.
AB  - Rat adenocarcinoma 13762 was modified by transfection to express IFN-gamma, and
      the tumor-forming potential of cytokine-producing cells was found to be
      dramatically impaired. Animals resistant to inocula of IFN-gamma-modified tumor
      were resistant to subsequent challenge with unmodified 13762 tumor. Induced
      immunity was tumor specific in that syngeneic but non-cross-reactive tumor grew
      with normal kinetics in animals injected with IFN-gamma-producing 13762 tumor.
      Antitumor T cells were derived from animals primed with IFN-gamma-producing 13762
      tumor and expanded into a cell line by coculture in vitro with IFN-gamma
      producing 13762 cells. Anti-13762-gamma T cells were cytotoxic in vitro toward
      IFN-gamma-producing 13762 tumor and were not reactive with other syngeneic tumors
      or spleen B cells. Anti-13762-gamma T cells were determined to be CD4+ by Ab
      staining and flow cytometric analysis, and recognition of 13762-gamma in vitro
      was inhibited by anti-MHC class II Ab. Anti-13762-gamma T cells were not reactive
      in vitro with wild-type 13762 tumor unless treated with exogenous rIFN-gamma,
      which induced expression of cell surface MHC class II. However, adoptively
      transferred anti-13762-gamma T cells could effect regression of wild-type 13762
      tumor or dramatically inhibit progressive growth in animals carrying significant
      tumor burden, and the antitumor phenotype did not require CD8+ T cells in vivo.
      These experiments demonstrate that although antitumor T cells elicited against
      cytokine-modified tumor may fail to demonstrate reactivity with unmodified tumor
      in vitro, antitumor properties may be manifest in vivo.

PMID- 7722314
TI  - IL-12 enhances Th1-type responses in human Leishmania donovani infections.
AB  - IL-12 is a pluripotent cytokine that interacts with NK and T cells to play a
      central role in the initiation and maintenance of Th1 responses and IFN-gamma
      production. Because of the interactive relationship between IL-12 and IFN-gamma
      response to infectious organisms, a study was undertaken to examine the role of
      IL-12 in the immune regulation of human visceral leishmaniasis (VL). Human (Hu)
      VL is associated with immune dysfunction and the appearance of IL-10 mRNA, not
      present in healed individuals. We found that PBMC from treated VL patients
      produced both IL-12 p40 and IFN-gamma in response to in vitro stimulation with
      Leishmania donovani. The production of both IL-12 p40 and IFN-gamma were
      interdependent and were abrogated by the addition of exogenous Hu rIL-10. In
      contrast, PBMC from active VL patients did not produce IL-12 p40 or IFN-gamma in
      response to L. donovani lysate. Neutralizing anti-IL-10 mAb led to the
      enhancement of IFN-gamma production by active VL PBMC cultured with L. donovani
      lysate, and this enhanced IFN-gamma production was blocked by anti-IL-12 mAb. The
      addition of exogenous Hu rIL-12 to PBMC from active VL patients resulted in the
      augmentation of IFN-gamma in response to L. donovani lysate. Therefore, treatment
      of active VL patient PBMC with anti-IL-10 or IL-12 shifted the response toward a
      Th1-type response with the production of IFN-gamma. These results indicate that
      IL-12 may play an important role in the regulation of the cellular immune
      responses in Hu VL.

PMID- 7722315
TI  - Multiple point mutations in an endogenous retroviral gene confer high
      immunogenicity on a drug-treated murine tumor.
AB  - Exposure in vivo of murine L5178Y lymphoma cells to cytoreductive triazene
      derivatives leads to the generation of immunogenic variant lines expressing new
      transplantation Ags recognized by CTL. In one such clonal variant (clone D), at
      least one subset of T cell neoepitopes are provided by proteins previously shown
      by serology to be products of endogenous retroviral env sequences. We report here
      on characterization of PCR-amplified gp70 env genes in clone D. Relative to known
      gp70 sequences in parental cells and in current databases, one gp70 sequence
      presented four distinct nucleotide changes, two of which were apparently unique
      to clone D DNA and cDNA upon differential hybridization analysis. Transfection
      experiments with the entire gp70 gene or subgenic fragments encompassing a single
      putative mutation showed that products of the mutated env gene or fragments may
      confer immunogenicity in vivo and susceptibility in vitro to lysis by clone D
      primed, H-2Kd- or H-2Ld-restricted CTL. By skin test assay of mice primed with
      either clone D or three mutated synthetic peptides, evidence was obtained that
      amino acid substitutions at the relevant positions of the gp70 protein may
      produce immunogenic T cell epitopes and that these epitopes are expressed in vivo
      by clone D. These data point to the role of mutated retroviral tumor peptides as
      rejection Ags in histocompatible hosts.

PMID- 7722316
TI  - CD8 T lymphocytes specific for the secreted p60 antigen protect against Listeria
      monocytogenes infection.
AB  - The ability of Listeria monocytogenes to gain access to the cytoplasm of infected
      cells results in the processing and presentation of bacterial Ags through the MHC
      class I pathway. As a result, CD8 T cells are the most effective mediators of
      acquired immunity in the mouse model of L. monocytogenes infection. CD8 T cells
      specific for a single nonamer epitope derived from the secreted virulence factor
      listeriolysin O (LLO) can protect H-2d mice against lethal infection. Bacteria
      lacking LLO are avirulent and do not elicit protective immunity in mice. Thus,
      the failure of LLO minus L. monocytogenes to elicit protective immunity could be
      caused either by their inability to enter the cytoplasm or to the lack of LLO
      derived peptide epitopes. In this report we provide evidence that H-2d restricted
      CD8 T cells with specificity for another L. monocytogenes protein, the secreted
      p60 molecule, can protect against infection. Our studies further demonstrate that
      LLO-dependent induction of protective immunity results from access of the
      bacterium to the cytoplasm. In addition, these studies provide support for the
      hypothesis that secreted bacterial proteins are the most important targets for
      protective CD8 T cell-mediated immunity.

PMID- 7722317
TI  - Synthetic oligonucleotide expressed by a recombinant vaccinia virus elicits
      therapeutic CTL.
AB  - P815A is a naturally occurring tumor rejection Ag of the methylcholanthrene
      induced murine mastocytoma P815. The gene encoding the Ag P815A, designated P1A,
      is identical to that encoded in the normal genome of the DBA/2 mouse. A
      recombinant vaccinia virus (rVV) was constructed that expressed a synthetic
      oligonucleotide encoding the minimal determinant peptide of the tumor-associated
      Ag. Although the rVV recombinant expressing this mini-gene was recognized
      efficiently in vitro, it was an ineffective immunogen in vivo. The addition of an
      endoplasmic reticulum insertion signal sequence to the NH2 terminus of the
      minimal determinant resulted in a rVV that elicited CD8+ T cells that could lyse
      P815 mastocytoma cells in vitro and that were therapeutic in vivo. Recombinant
      viruses expressing synthetic oligonucleotide sequences preceded by the insertion
      signal sequences allow the expression of Ag directly into the endoplasmic
      reticulum, where binding to MHC class I molecules is most efficient. Vaccines
      based on synthetic oligonucleotides could be constructed with ease and rapidity
      but, most importantly, such constructs avoid the dangers associated with the
      expression of full length genes encoding TAA that are potentially oncogenic.

PMID- 7722318
TI  - IL-12 modulation of T helper responses to the filarial helminth, Brugia malayi.
AB  - The purpose of the current study was to evaluate the effects of exogenous IL-12
      on: 1) development of the Th cell response to Brugia malayi microfilariae (mf);
      2) established B. malayi-specific Th2 responses; and 3) resistance to mf. IL-12
      given at the time of inoculation with live mf resulted in a switch in development
      from a dominant Th2 (IL-4, IL-5 >> IFN-gamma) to a dominant Th1 response (IFN
      gamma >> IL-4, IL-5). Induction of Th1 activity by IL-12 was dependent on IFN
      gamma in vivo. When mice were given IL-12 (0.5 microgram daily for 4 days) after
      mf Ag-specific Th2 responses had been established, Ag-driven IL-4 and IL-5
      production by spleen and peritoneal cells were reduced respectively by
      approximately 75 to 90% and approximately 30 to 40%, IFN-gamma production was
      elevated, and 68% fewer eosinophils were recovered from the peritoneal cavity. In
      vivo depletion of IFN-gamma ablated the effects of IL-12 on both cytokine
      production and eosinophil recovery. IL-12 treatment of either naive or previously
      sensitized mice challenged intravenously with live B. malayi did not alter the
      rate of clearance of mf from the blood. These data indicate that IL-12 treatment
      suppresses induction of filarial driven Th2 responses and modulates recall
      responses of established Th2 cells, but does not alter elimination of blood-borne
      mf in nonimmune or immune mice.

PMID- 7722319
TI  - Mapping of T cell epitopes of the 30-kDa alpha antigen of Mycobacterium bovis
      strain bacillus Calmette-Guerin in purified protein derivative (PPD)-positive
      individuals.
AB  - The fibronectin-binding 30-kDa alpha Ag is a major secretory protein of growing
      mycobacteria that stimulates in vitro lymphocyte blastogenesis in most healthy
      purified protein derivative-positive individuals, but only a minority of patients
      with active tuberculosis. T cell epitopes of the alpha Ag were assessed using
      blastogenic responses of PBMC from 12 healthy purified protein derivative
      positive subjects to a set of synthetic peptides based on the 325-amino acid
      sequence of the alpha Ag of Mycobacterium bovis BCG. Because epitope-specific
      precursor cells are infrequent and randomly distributed, we used Poisson analysis
      to determine positive responses to 10 micrograms/ml of each peptide in 12
      replicate culture wells. Seven immunodominant regions of the alpha Ag were
      identified. Each subjects responded to at least one of the two most dominant
      epitopes, which correspond to amino acids 131-155 and 233-257 (from N terminus).
      Peptides of these two epitopes induced production of IFN-gamma by sorted CD4+ T
      cells. The immunodominant peptides may have use a components of a vaccine and as
      tools to study the evolution of the immune response to M. tuberculosis. The two
      most dominant epitopes both occur in regions of the alpha Ag that differ from
      those of the atypical pathogens M. avium and M. kansasii. In addition, the M.
      bovis epitope of amino acids 133-155 differs from that of M. tuberculosis by a
      single amino acid. It may be possible to exploit the sequence differences for
      development of diagnostic tests with increased specificity.

PMID- 7722320
TI  - IL-4 treatment can cure established gastrointestinal nematode infections in
      immunocompetent and immunodeficient mice.
AB  - We examined the ability of a long acting formulation of IL-4 (IL-4/anti-IL-4 mAb
      complexes) to limit established infections of normal and immune deficient mice
      with two nematode parasites: Heligmosomoides polygyrus and Nippostrongylus
      brasiliensis. IL-4, at a dose of 5 to 20 micrograms every 3 to 4 days, rapidly
      decreased egg production and, over a period of 6 to 9 days, terminated infection
      in H. polygyrus-inoculated BALB/c mice. IL-4 treatment also considerably
      decreased egg production in H. polygyrus-inoculated CB.17 severe combined
      immunodeficient (SCID) mice and terminated infection in N. brasiliensis
      inoculated SCID mice and anti-CD4 mAb-treated BALB/c mice. IL-4 was less
      effective at limiting H. polygyrus infection if administrated when parasites were
      in larval stages than if administered after adult worms had developed. The
      effects of IL-4 were inhibited completely by an mAb that specifically blocks the
      mouse IL-4R. These observations demonstrate that IL-4 can limit the fecundity and
      survival of gastrointestinal nematode parasites through effects on the host that
      are independent of the specific immune system.

PMID- 7722322
TI  - Vaccination routes that fail to elicit protective immunity against Schistosoma
      mansoni induce the production of TGF-beta, which down-regulates macrophage
      antiparasitic activity.
AB  - C57BL/6 mice immunized intradermally (i.d.) with bacillus Calmette Guerin (BCG)
      plus killed skin-stage schistosomula are protected against subsequent infection
      with Schistosoma mansoni, whereas immunization by i.v. or i.m. routes is not
      protective. Moreover, previous immunization via the nonprotective i.v. route
      interfered with the ability to subsequently induce protection by i.d.
      vaccination, suggesting that inhibitory responses are invoked. Given the evidence
      that activated macrophages (M phi) play a role as effector cells in protection
      against schistosomiasis, we investigated the ability of spleen cells from
      protected and nonprotected immunized mice to produce M phi activating and
      deactivating cytokines. Exposure to supernatant fluids (SNs) from Ag stimulated
      spleen cells of i.d., but not i.v. or i.m., immunized mice activated inflammatory
      M phi for in vitro killing of schistosome larvae, through a mechanism dependent
      on both IFN gamma and TNF-alpha. No evidence was observed for the preferential
      induction of the M phi activating Th1 cytokines IFN-gamma and IL-2 in i.d.
      immunized mice, nor did spleen cells from nonprotected animals produce higher
      levels of the Th2 associated cytokines IL-4 and IL-10, which are known to prevent
      M phi activation. TGF-beta was, however, detected in SNs from unprotected mice.
      Moreover, the M phi inhibitory activity detected in these SNs was heat stable and
      neutralized by anti-TGF-beta Abs, suggesting that production of TGF-beta is at
      least partially responsible for the failure of i.m. and i.v. immunized mice to
      develop immunity to S. mansoni. Thus, the induction of down-regulatory cytokines
      may be an important factor limiting the efficacy of certain vaccination
      protocols.

PMID- 7722321
TI  - Active immunotherapy of cancer with a nonreplicating recombinant fowlpox virus
      encoding a model tumor-associated antigen.
AB  - Some tumor cells express Ags that are potentially recognizable by T lymphocytes
      and yet do not elicit significant immune responses. To explore new
      immunotherapeutic strategies aimed at enhancing the recognition of these tumor
      associated Ags (TAA), we developed an experimental mouse model consisting of a
      lethal clone of the BALB/c tumor line CT26 designated CT26.WT, which was
      transduced with the lacZ gene encoding beta-galactosidase, to create CT26.CL25.
      The growth rate and lethality of CT26.CL25 and CT26.WT were virtually identical
      despite the expression by CT26.CL25 of the model tumor Ag in vivo. A recombinant
      fowlpox virus (rFPV), which is replication incompetent in mammalian cells, was
      constructed that expressed the model TAA, beta-galactosidase, under the influence
      of the 40-kDa vaccinia virus early/late promoter. This recombinant, FPV.bg40k,
      functioned effectively in vivo as an immunogen, eliciting CD8+ T cells that could
      effectively lyse CT26.CL25 in vitro. FPV.bg40k protected mice from both
      subcutaneous and intravenous tumor challenge by CT26.CL25, and most surprisingly,
      mice bearing established 3-day pulmonary metastasis were found to have
      significant, Ag-specific decreases in tumor burden and prolonged survival after
      treatment with the rFPV. These observations constitute the first reported use of
      rFPV in the prevention and treatment of an experimental cancer and suggest that
      changing the context in which the immune system encounters a TAA can
      significantly and therapeutically alter the host immune response against cancer.

PMID- 7722323
TI  - IL-12 enhances vaccine-induced immunity to Schistosoma mansoni in mice and
      decreases T helper 2 cytokine expression, IgE production, and tissue
      eosinophilia.
AB  - Vaccination of mice with radiation-attenuated cercariae of Schistosoma mansoni
      results in a highly significant but partial protection against challenge
      infection. This immunity is dependent on CD4+ T cells, and because of its
      suppression by anti-IFN-gamma, appears to be caused by a Th1 response.
      Nevertheless, both Th1 and Th2 lymphokines are expressed in vaccinated and
      challenged mice, and we hypothesized that the expression of the latter group of
      down-regulatory cytokines may be responsible for the failure to obtain complete
      protection. Because IL-12 is a key cytokine that suppresses Th2-like responses,
      we asked whether IL-12 could increase vaccine-induced immunity to S. mansoni.
      Indeed, administration of IL-12 significantly reduced worm burdens following a
      challenge infection. IL-12-treated animals displayed a marked increase in
      pulmonary IFN-gamma and IL-12 p40 mRNA expression, while levels of IL-4, IL-5,
      and IL-13 were suppressed significantly during the period of vaccination. A
      marked decrease in serum IgE and tissue eosinophilia, two responses regulated by
      Th2 cytokines, was also observed. Surprisingly, IL-12-treated/vaccinated mice
      failed to demonstrate a significant increase in IFN-gamma, TNF-alpha, or nitric
      oxide synthase mRNA at the time of challenge infection when compared with
      vaccinated controls, but did, however, display significantly suppressed Th2
      cytokine mRNA production. Together, these data demonstrate that exogenous IL-12
      regulates Th1/Th2 responses during immunization with irradiated cercariae, and
      suggest that this cytokine may be used to increase vaccine-induced immunity to S.
      mansoni.

PMID- 7722324
TI  - Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of
      survival and activation outcomes.
AB  - We examined the direct effects of glucocorticoid treatment on neutrophil survival
      and function in vitro. Four different glucocorticoids caused a dose-dependent
      inhibition of apoptosis leading to increased survival of neutrophils. Maximal
      effects were found with dexamethasone at 10(-6) M, 16.6 +/- 6.2 vs 54.6 +/- 6.9,
      at 24 h (p < 0.05). Nonglucocorticoid steroids did not modulate apoptosis in
      neutrophils. Furthermore, the effect was inhibited in a dose-dependent manner by
      the glucocorticoid antagonist RU 486. Glucocorticoid-treated neutrophils produced
      significantly more superoxide in response to FMLP than untreated controls (p <
      0.05). However, both basal and stimulated superoxide production were less than
      that found with freshly isolated cells. Such lack of priming or activation by
      glucocorticoids is in contrast to previous experience when increased survival was
      accompanied by cell activation. When compared with other stimuli, the effect of
      glucocorticoids at 24 h was similar to that of LPS but less than that of
      granulocyte-macrophage colony-stimulating factor (GM-CSF), 52 +/- 4, 57 +/- 6,
      and 70 +/- 4, respectively (p < 0.05). When added in combination, dexamethasone
      did not increase survival with LPS, but did augment the effect of GM-CSF,
      suggesting diversity in the mechanisms by which these stimuli regulate apoptosis.
      These data indicate that glucocorticoids can augment the effector potential of
      neutrophils by prolonging their survival and functional responsiveness, and such
      treatment might be detrimental in vivo because of delay in neutrophil apoptosis
      and in ultimate clearance of them from tissues.

PMID- 7722325
TI  - Human polymorphonuclear leukocytes store large amounts of terminal complement
      components C7 and C6, which may be released on stimulation.
AB  - Secretion of the C factors C7, C6, and C3 by human polymorphonuclear leukocytes
      (PMNs) and PBMCs was studied by ELISA and immunoblot. The release of C7 and C6 by
      PMNs during 24 h of culture was 16-fold and 6-fold higher, respectively, than the
      C3 release, with median concentrations of 50.2 ng/ml, 18.3 ng/ml, and 3.1 ng/ml,
      respectively. In PBMC cultures, C release was considerably lower, and there was a
      different secretory pattern with a 6-fold higher release of C3 compared with C7
      and C6. Stimulation with PMA led to a more rapid and complete secretion of the
      components to the culture media, whereas treatment with unopsonized Candida
      species did not affect the release. PMN release of C factors was not dependent on
      protein biosynthesis, and there was no indication of a selective uptake of C7
      from serum as demonstrated by incubating PMNs from a subject with allotype C7 N
      in C7 M serum. Thus, the C components were probably produced by the PMNs or their
      bone marrow precursors before ex vivo culture. In cell lysates of freshly
      isolated cells, median C7, C6, and C3 contents of 1 x 10(7) PMNs were 149.7,
      60.1, and 10.4 ng/ml, respectively, whereas the corresponding values for 1 x
      10(7) PBMCs were 3.2, 2.6, and 14.6 ng/ml, respectively. The C6 and C7 were shown
      to incorporate into the terminal complement complex, and their molecular
      integrity was supported by identical m.w. to C6 and C7 present in normal serum.
      PMNs may represent a major source of C7 and C6 and may be more important than
      monocytes or macrophages in contributing terminal C components at a site of
      inflammation. This suggests a new role for the PMN as a C membrane attack
      modulator.

PMID- 7722326
TI  - Eosinophil major basic protein induces degranulation and IL-8 production by human
      eosinophils.
AB  - Eosinophil granule proteins, such as major basic protein (MBP), eosinophil
      peroxidase (EPO), and eosinophil cationic protein (ECP), possess a wide range of
      biologic activities including the ability to activate other cells, such as
      basophils, neutrophils, and platelets. Here we have analyzed the effects of these
      proteins on eosinophils themselves. MBP and EPO, at concentrations as low as 0.1
      micrograms/ml, induced eosinophil degranulation as measured by release of
      eosinophil-derived neurotoxin (EDN); in contrast, ECP, at 1 micrograms/ml, was
      inactive. MBP (10 micrograms/ml) and EPO (0.1 micrograms/ml) induced EDN release
      comparable with one of the strongest agonists for eosinophils, secretory IgA.
      Pretreatment of cells with dibutyryl cAMP or cytochalasin B completely abolished
      the EDN release induced by MBP and EPO, suggesting that the effects of MBP and
      EPO are not due to cytotoxic lysis of the cells. Degranulation induced by MBP was
      only partially dependent on calcium, and no elevation of intracellular Ca2+
      concentration ([Ca2+]i) was observed in eosinophils stimulated with MBP. MBP
      stimulated the production, up to eightfold, of IL-8 by eosinophils in a dose
      dependent manner. The MBP-stimulated expression of IL-8 mRNA by eosinophils was
      confirmed by reverse transcription-PCR. The MBP-stimulated production of IL-8 was
      inhibited by actinomycin D, but not by cyclosporin A. Furthermore, MBP and
      calcium ionophore ionomycin synergistically induced production of leukotriene C4
      from eosinophils. Thus, MBP and EPO may act as autocrine mediators in the
      pathogenesis of eosinophil-associated diseases, such as bronchial asthma.

PMID- 7722327
TI  - TNF-alpha induces tyrosine phosphorylation of mitogen-activated protein kinase in
      adherent human neutrophils.
AB  - Recombinant human TNF-alpha induces increased tyrosine phosphorylation of several
      proteins in human neutrophils (PMN) adhered to serum-coated plastic. When PMN are
      kept in suspension, TNF does not induce significant tyrosine phosphorylation. In
      adherent PMN, a 42-kDa protein (p42) displayed the most striking increase in
      tyrosine phosphorylation after TNF stimulation. Cell lysates of TNF-stimulated
      PMN were separated by two-dimensional gel electrophoresis and were immunoblotted
      with either anti-phosphotyrosine (alpha-PY) mAb or anti-mitogen-activated protein
      kinase (alpha-MAPK) mAb. Both Abs detected p42, and the spots were
      superimposable. Cell lysates were immunoprecipitated with agarose-conjugated
      alpha-PY mAb, electrophoresed, and then immunoblotted with alpha-MAPK Ab;
      alternatively, cell lysates were immunoprecipitated with agarose-conjugated alpha
      MAPK Ab, electrophoresed, and then immunoblotted with alpha-PY mAb. In both
      cases, p42 was detected. These results demonstrate that p42 is a member of the
      MAPK family. TNF induces a time-and dose-dependent increase in tyrosine
      phosphorylation of p42 and MAPK activity. The degree of p42 tyrosine
      phosphorylation parallels the level of MAPK activity. MAPK activity was
      determined by measuring 32P phosphorylation of a synthetic peptide containing the
      recognition site on myelin basic protein for MAPK. PMN pretreatment with
      genistein, a tyrosine kinase inhibitor, inhibited the TNF-induced increase in
      tyrosine phosphorylation and MAPK activity. These results indicate that TNF
      signaling involves activation of MAPK.

PMID- 7722328
TI  - Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung
      injury in rats.
AB  - The role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the
      pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG
      immune complexes or intratracheal administration of LPS has been assessed.
      Critical to these studies was the cloning and functional expression of rat MIP-1
      alpha. The resulting product shared 92% and 90% homology with the known murine
      sequence at the cDNA level and protein level, respectively. Recombinant rat MIP-1
      alpha exhibited dose-dependent chemotactic activity for both rat and human
      monocytes and neutrophils, which could be blocked by anti-murine MIP-1 alpha Ab.
      Rat MIP-1 alpha mRNA and protein expression were determined as a function of time
      in both injury models. A time-dependent increase in MIP-1 alpha mRNA in lung
      extracts was observed in both models. In the LPS model, MIP-1 alpha protein could
      also be detected in bronchoalveolar lavage (BAL) fluids by Western blot analysis.
      Anti-MIP-1 alpha administered at commencement of IgG immune complex- or LPS
      induced injury resulted in significant reductions in BAL neutrophils as well as
      in injury as measured by pulmonary vascular permeability. Under such conditions,
      in both models TNF-alpha content in BAL fluids was substantially reduced as
      compared with BAL fluids from positive control animals. These findings suggest
      that rat MIP-1 alpha plays an important role in the development of lung injury in
      these neutrophil-dependent models. The role of MIP-1 alpha seems to be related to
      production of TNF-alpha, which in turn up-regulates vascular adhesion molecules
      required for neutrophil influx.

PMID- 7722329
TI  - Molecular basis of the complement C7 M/N polymorphism. A neutral amino acid
      substitution outside the epitope of the allospecific monoclonal antibody WU 4-15.
AB  - The allotypes of the C7 M/N polymorphism are determined by comparing the ELISA
      reaction pattern of the allospecific mAb WU 4-15 with polyclonal anti-C7 IgG. To
      characterize the molecular basis of this polymorphism, the WU 4-15 epitope was
      mapped by expression of cDNA fragments. It was found to be located within the
      boundary region of the two short consensus repeats of C7 (amino acid residues 595
      612). Coincidentally an A or C substitution was found in the course of
      investigation of the gene structure at nucleotide 1759. This leads to an
      electrically neutral Pro/Thr substitution at residue 565 and alternative Sau961
      or RsaI restriction sites, respectively. Enzymatic digestion or sequencing of PCR
      amplified genomic DNA from C7 M/N-typed individuals showed a perfect
      correspondence of the genotype with the phenotype of the C7 M/N polymorphism. In
      contrast, no association was found with the genotypes of a second polymorphic
      site at residue 367. Thus, a threonine at amino acid residue 565 allows access of
      WU 4-15 to its epitope but its substitution with proline almost completely
      inhibits access in the native molecule, although the epitope is about 40 amino
      acid residues distant from the polymorphic site in the primary structure.
      Furthermore, the different conformational structure is probably responsible for
      the hypomorphic appearance of C7*N.

PMID- 7722330
TI  - T cell cytokine mRNA expression during the course of the immunopathologic ocular
      disease herpetic stromal keratitis.
AB  - Corneal infection with herpes simplex virus in mice induces an inflammatory
      response in the stroma (herpetic stromal keratitis (HSK)) that appears to
      represent an immunopathologic reaction in which T cells of the CD4+ subset act as
      the essential participants. To assess the role of T cell cytokines at different
      clinical phases of HSK, corneas and draining lymph node (DLN) cells were
      collected and the levels of mRNA thought to be representative of type 1 and type
      2 T cells were quantitated by reverse transcription-PCR. In the corneas collected
      before the onset of clinical disease, IFN-gamma and IL-4 mRNA were detectable,
      with levels of IFN-gamma 5- to 15-fold higher than IL-4. During the onset and
      peak expression of clinical disease, type 1 cytokines IFN-gamma and IL-2 were
      predominant in the corneas, and IL-4 levels were either very low or undetectable.
      Neither IL-10 nor IL-5 mRNA was present. After 3 wk postinfection, when some
      animals with mild disease began to recover, high levels of type 2 cytokine mRNA,
      particularly IL-10, were present. In addition, only during the recovery phase was
      IL-10 mRNA present in DLN samples. Levels of transcriptional activity for
      cytokine mRNA during clinical HSK were higher in corneas than in the
      corresponding DLN samples. The results indicate that IL-10 may be involved in HSK
      resolution and that the stimuli for cytokine induction in the cornea may differ
      from those in the DLN.

PMID- 7722331
TI  - Periocular inflammation in mice with experimental systemic lupus erythematosus. A
      new experimental blepharitis and its modulation.
AB  - Experimental systemic lupus erythematosus (SLE) can be induced in mice by
      immunization with a human monoclonal anti-DNA Ab, bearing a major Id 16/6Id.
      Immunized mice initially produce Abs to 16/6Id, DNA and nuclear Ags, and
      subsequently develop various clinical manifestations including leukopenia and
      renal immune complex disease. MHC class I Ags play a critical role in the
      induction and progression of experimental SLE. The present study reports that
      ocular changes also occur in mice with experimental SLE. The ocular disease is
      characterized by bilateral subacute and chronic inflammation of the eyelids
      (blepharitis) with immune complex IgG deposition and hypertrophic meibomian
      glands. The severity of ocular changes was strain dependent: most severe in 129
      mice, less intense in BALB/c animals and only minimal in C3H.SW mice. No
      blepharitis developed in mice deficient in MHC class I expression. Further, the
      disease was strongly inhibited in BALB/c mice treated with methimazole, an agent
      that has been shown to repress transcription of MHC class I. In these cases,
      there was no IgG deposition and a decreased infiltration of inflammatory cells in
      the eyelids. These observations thus suggest that, similar to the observation
      with experimental SLE, MHC class I is critical in the onset of this experimental
      autoimmune blepharitis. The new experimental eye disease described here provides
      an animal model for chronic blepharitis in humans, a common condition for which
      such a model has been sought.

PMID- 7722332
TI  - T cell receptor repertoire differences between African Americans and Caucasians
      associated with polymorphism of the TCRBV3S1 (V beta 3.1) gene.
AB  - The generation of TCR diversity occurs primarily through rearrangement of
      germline DNA. Genetic polymorphism of the TCR chains appears to be a rarer
      mechanism for generating repertoire differences between races. Flow cytometric
      analysis of the TCR V beta repertoire in a population of healthy African
      Americans (n = 30) and Caucasians (n = 30) revealed a significant difference in
      the frequency of cells bearing V beta 3.1, but not V beta 2, V beta 5.1, V beta
      5.2-5.3, V beta 6.7, V beta 8.1-8.2, V beta 12.1, V beta 13.3, or V beta 19.
      African Americans had a significantly lower frequency of V beta 3.1+ cells, in
      both the CD4+ (2.55 +/- 0.36% vs 4.85 +/- 0.43%, p = 0.0001) and the CD8+ (3.03
      +/- 0.54% vs 5.32 +/- 0.57%, p = 0.004) population than did Caucasians, and this
      difference was independent of the age of the individuals. Analysis of genomic DNA
      revealed that the observed difference in frequency of V beta 3.1+ cells
      correlated with a recently described polymorphism of the recombination signal
      sequence of the TCRBV3S1 gene. Allele 1, associated with a lower frequency of V
      beta 3.1+ cells, was more commonly present in African Americans (0.68 vs 0.43),
      whereas allele 2, associated with a higher frequency of V beta 3.1+ cells, was
      more commonly present in Caucasians (0.31 vs 0.56). This study demonstrates the
      potential for TCR repertoire differences, based on genetic polymorphism, between
      African Americans and Caucasians.

PMID- 7722333
TI  - Cleavage of lymphocyte surface antigens CD2, CD4, and CD8 by polymorphonuclear
      leukocyte elastase and cathepsin G in patients with cystic fibrosis.
AB  - Polymorphonuclear leukocytes (PMN) accumulating in airways of patients with
      cystic fibrosis (CF) as a response to chronic endobronchial bacterial lung
      infection, release lysosomal serine proteinases such as PMN-elastase at
      concentrations of approximately 0.5 microM to 5 microM into the airway lumen.
      Immunohistology of CF lung material and fluorescence activated cell sorter
      analysis of sequential CF bronchoalveolar lavages demonstrated loss of the CD4
      and CD8 Ag on CD3+ T lymphocytes in sputum-filled airways. In 10 CF sputum
      samples 1.0%, 19.1%, and 15.7% of all CD3+ T lymphocytes expressed CD4, CD8, and
      CD2, respectively. Incubation of CF sputum supernatant fluids with peripheral
      blood T lymphocytes resulted in total reduction of CD4 and CD8 but not CD2.
      Addition of alpha 1-proteinase inhibitor abolished surface Ag cleavage
      completely. Purified PMN-elastase and cathepsin G cleaved CD2, CD4, and CD8 on
      peripheral blood T lymphocytes at proteinase concentrations of 0.83 to 8.3 microM
      in a dose-dependent manner. Cleaved CD4 and CD8 were reexpressed on the surface
      of T lymphocytes after 24 h in the absence of PMN-elastase. Incubation of a CD4+
      T cell clone with PMN-elastase lead to a significant reduction of cytotoxicity
      toward target cells and significantly reduced IL-2 and IL-4 production. The
      results suggest a temporary functional impairment of T lymphocytes in foci of
      high inflammation characterized by stimulated PMN, which may lower tissue
      destruction.

PMID- 7722334
TI  - Induction of IL-10 gene expression in human keratinocytes by UVB exposure in vivo
      and in vitro.
AB  - Numerous studies have demonstrated that ultraviolet B (UVB) irradiation has
      profound effects on the skin and systemic immune systems. Because many of the
      effects of UVB result in suppression of contact sensitivity responses and because
      IL-10 induces a Th2 rather than a Th1 response, we sought to determine whether
      UVB irradiation induces IL-10 transcription and subsequent protein secretion by
      human epidermal cells. Skin of nine volunteers was exposed to UVB or sham
      irradiation, and epidermal cell suspensions were prepared from suction blister
      roofs 24 h thereafter. mRNA was extracted using oligo dT-coated magnetic beads,
      and IL-10 cDNA was amplified with a sensitive RT-PCR technique. We found that IL
      10 was constitutively expressed by epidermal cells in 5 of 9 volunteers and that
      IL-10 message was up-regulated by UVB exposure in all experiments. Since
      epidermis consists of a heterogeneous cell population with distinct cytokine
      profiles, we determined whether UVB caused enhanced IL-10 transcription and
      protein secretion in human keratinocyte cultures. In these experiments, IL-10 was
      constitutively expressed by keratinocytes and UVB up-regulated IL-10 gene
      expression in a dose-dependent manner 24 h after in vitro irradiation, coinciding
      with IL-10 protein secretion into the culture supernatants. Taken together, the
      findings indicate that UVB irradiation induces IL-10 in human keratinocytes and
      suggest that keratinocyte-derived IL-10 may be an important component of the
      immunosuppression that results from UVB irradiation.

PMID- 7722335
TI  - Murine and human antibodies to native DNA that cross-react with the A and D SnRNP
      polypeptides cause direct injury of cultured kidney cells.
AB  - Murine monoclonal and human affinity-purified Abs to native DNA (anti-nDNA) that
      cross-react with the A and D SnRNP polypeptides were analyzed for direct
      injurious effects against cultured pig kidney (PK15) cells under ordinary cell
      culture conditions. Of the two murine nephritogenic Abs derived from NZB/NZW F1
      mice (BWds1 and BWds3), BWds1 initially bound to the cell surface and
      subsequently penetrated into cells localizing in nuclei and cytoplasm. BWds3 was
      consistently and abundantly associated with the surface of live cells without
      penetration. In the presence of rabbit C, BWds3 caused massive cell lysis (85%
      dead cells) whereas BWds1 had only a modest lytic effect (24% dead cells). One of
      the nonpathogenic murine anti-nDNA Abs (5GD5) that did not cross-react with the A
      and D polypeptides showed no interaction with PK-15 cells and had no injurious
      effects. Affinity-purified autoantibodies to nDNA isolated from two SLE patients
      with high anti-nDNA titers and clinically active lupus nephritis showed
      properties similar to the murine mAbs. They both strongly cross-reacted with the
      A and D SnRNP polypeptides and interacted with live PK-15 cells. One of them (Cr)
      penetrated into live cells and localized within cytoplasm and nuclei whereas the
      other (Pe) bound mostly to the cell surface and caused significant cell lysis in
      the presence of C. Results of this study suggest that the nephritogenic murine
      anti-nDNA as well as subpopulations of human anti-nDNA Abs could exert their
      injurious influence through direct interactions with kidney cells using two
      different pathogenic mechanisms (i.e., C-mediated cytotoxicity and potential cell
      cycle dysfunctions. Interestingly, cross-reactivity of anti-nDNA Abs with the A
      and D SnRNP polypeptides appears to be a prerequisite for their direct
      pathogenicity.

PMID- 7722336
TI  - Induction of experimental autoimmune sialoadenitis by immunization of PL/J mice
      with carbonic anhydrase II.
AB  - Experimental autoimmune sialoadenitis was induced in PL/J (H-2u) mice by
      intradermal immunization with human carbonic anhydrase II (CAII) and adjuvant
      containing monophosphoryl lipid A and trehalose diorynomycolate. Mice immunized
      with CAII showed a significant increase in the number and size of foci with
      lymphocytic infiltration in the salivary gland compared with mice immunized with
      adjuvant alone and untreated mice. In mice immunized with CAII, lymphocytic foci
      were observed around intercalated and intralobular ducts in the salivary glands,
      resulting in atrophy and replacement of acinar units. The epithelial cells of
      salivary ducts adjacent to the lymphocytic foci showed both degenerative and
      regenerative changes. Similar lymphocytic infiltrations were observed in the
      pancreas and kidney of a few mice immunized with CAII. Among several mouse
      strains with different H-2 haplotypes (p, q, r, s, and u), strains bearing H-2s
      and H-2u were susceptible to CAII-induced sialoadenitis. These results indicate
      that sialoadenitis induced by the immunization of CAII in mice may serve as a
      disease model of Sjogren's syndrome and that CAII or its derived peptides in
      association with the MHC may be one Ag recognized by an autoimmune response in
      this syndrome.

PMID- 7722337
TI  - IFN-gamma gene expression in pancreatic islet-infiltrating mononuclear cells
      correlates with autoimmune diabetes in nonobese diabetic mice.
AB  - Insulin-dependent diabetes mellitus in nonobese diabetic (NOD) mice results from
      selective destruction of pancreatic islet beta-cells following islet infiltration
      by mononuclear leukocytes. Cytokines produced by islet-infiltrating mononuclear
      cells may be involved in beta-cell destruction. Therefore, we analyzed cytokine
      mRNA expression, by reverse-transcriptase PCR (RT-PCR) assay, in mononuclear
      leukocytes isolated from pancreatic islets of four groups of mice: diabetes-prone
      female NOD mice; female NOD mice protected from diabetes by injection of CFA at
      an early age; male NOD mice with a low diabetes incidence; and female BALB/c mice
      that do not develop diabetes. We found that mRNA levels of IL-1 beta, IL-2, IL-4,
      IL-10, and IFN-gamma in mononuclear cells from islets of diabetes-prone female
      NOD mice increased progressively as these cells infiltrated the islets from age 5
      wk to diabetes onset (> 13 wk). However, only IFN-gamma mRNA levels were
      significantly higher in islet mononuclear cells from 12-wk-old diabetes-prone
      female NOD mice than from less diabetes-prone NOD mice (CFA-treated females, and
      males) and normal mice (BALB/c). In contrast, IL-4 mRNA levels were lower in
      islet mononuclear cells from diabetes-prone female NOD mice than from NOD mice
      with low diabetes incidence (CFA-treated females and males). Splenic cell mRNA
      levels of IFN-gamma and IL-4 were not different in the four groups of mice. These
      results suggest that islet beta-cell destruction and diabetes in female NOD mice
      are dependent upon intra-islet IFN-gamma production by mononuclear cells, and
      that CFA-treated female NOD mice and male NOD mice may be protected from diabetes
      development by down-regulation of IFN-gamma production in the islets.

PMID- 7722338
TI  - Increased frequency of gamma delta T cells in cerebrospinal fluid and peripheral
      blood of patients with multiple sclerosis. Reactivity, cytotoxicity, and T cell
      receptor V gene rearrangements.
AB  - Infiltrating gamma delta T cells are potentially involved in the central nervous
      system demyelination in multiple sclerosis (MS). To further study this
      hypothesis, we analyzed the frequency and functional properties of gamma delta T
      cells in peripheral blood (PB) and paired cerebrospinal fluid (CSF) of patients
      with MS and control subjects, including patients with other neurologic diseases
      (OND) and healthy individuals. The frequency analysis was performed under
      limiting dilution condition using rIL-2 and PHA. After PHA stimulation, a
      significantly increased frequency of gamma delta T cells was observed in PB (14.7
      x 10(-4)) and in CSF (15.8 x 10(-4)) of MS patients as compared with 4.3 x 10(-4)
      in PB and 3.9 x 10(-4) detected in CSF of patients with OND. The frequency was
      represented equally in OND patients and normal individuals. Similarly, the IL-2
      responsive gamma delta T cells occurred at a higher frequency in PB of control
      subjects (1.1 x 10(-4)) in OND patients and 1.5 x 10(-4) in normal individuals).
      Forty-three percent (13 of 30) of the gamma delta T cell clones isolated from PB
      and CSF of MS patients responded to heat shock protein (HSP70) but not HSP65,
      whereas only 2 of 30 control gamma delta T cell clones reacted to the HSP. The
      majority of the gamma delta T cell clones were able to induce non-MHC-restricted
      cytolysis of Daudi cells. All clones displayed a substantial reactivity to
      bacterial superantigens staphylococcal enterotoxin B and toxic shock syndrome
      toxin-1, irrespective of their gamma delta V gene usage. Furthermore, the gamma
      delta T cell clones expressed predominantly TCRDV2 and GV2 genes (26 of 35
      clones), whereas the clones derived from CSF of MS patients expressed either DV1
      or DV2 genes. The obtained gamma delta clones, in general, represented rather
      heterogeneous clonal origins, even though a predominant clonal origin was found
      in a set of 10 gamma delta clones derived from one patient with MS. The present
      study provides new evidence supporting a possible role of gamma delta T cells in
      the secondary inflammatory processes in MS.

PMID- 7722339
TI  - Electrophoretic karyotype of intracellular yeast-like symbiotes in rice
      planthoppers and anobiid beetles.
AB  - Chromosomal DNA molecules of intracellular yeast-like symbiotes (YLS) of three
      species of rice planthoppers and two species of anobiid beetles have been
      separated by pulsed-field gel electrophoresis. Probable chromosome numbers of
      Nilaparvata lugens, Sogatella furcifera, and Laodelphax striatellus, were 4, 4,
      and 5, respectively, and tentative genome sizes were 17.3, 17.6, and 20.1 Mbp,
      respectively, based upon migration of individual chromosome-sized DNA relative to
      the size standards of Schizosaccharomyces pombe, Hansenula wingei, and
      Saccharomyces cerevisiae chromosomes. Chromosome numbers of Lasioderma serricorne
      and Stegobium paniceum were 11 and 15, respectively, and total genome sizes were
      20.9 and 15.1 Mbp, respectively. The chromosomes carrying ribosomal RNA genes
      were identified by Southern blot analysis. Chromosomal organization and the
      genome size of YLS were similar to those of nonsymbiotic yeasts and fungi.

PMID- 7722340
TI  - Bacterial entomopathogens from the Drosophila paulistorum semispecies complex.
AB  - Bacteria which are infectious by inoculation in lepidoptera have been isolated
      and characterized from semispecies comprising the Drosophila paulistorum complex.
      These microorganisms are pathogenic toward lepidopteran hosts such as Heliothis
      virescens when introduced by injection of Drosophila tissue extracts and have
      been given the trivial name DpLE (D. paulistorum lepidopteran entomopathogen).
      The DpLE from two of the semispecies, Transitional and Andean, were determined to
      be related to Proteus vulgaris based upon nucleotide sequence comparisons of 16S
      rDNA genes. Infectivity and 16S rDNA-based PCR assays showed the bacterium to be
      localized in a number of drosophilid tissues except adult heads and thoraces.
      Based upon similar experiments, the DpLE in transinfected Heliothis larvae were
      found in all tissues assayed prior to the onset of mortality. Stocks of
      Drosophila which had spontaneously lost DpLE continued to produce sterile sons
      when crossed with incompatible semispecies' females, confirming that the
      bacilliform DpLE is not the causative agent of the Drosophila paulistorum
      intersemispecific hybrid male sterility. Acquisition of the sequences of the 16S
      rDNA molecules of DpLE from all six semispecies permitted the construction of a
      phylogenetic tree in which the groupings were found not to be congruent with the
      phylogenies of their insect hosts.

PMID- 7722341
TI  - Wound repair in the Amphioxus (Branchiostoma platae), an animal deprived of
      inflammatory phagocytes.
AB  - The existence of phagocytes in the Amphioxus is a matter of debate since early
      studies of Metchnikoff, who could not induce inflammation in this animal. To
      reinvestigate this important phenomenon, we sectioned the distal portion of the
      animal and analyzed, by morphological methods, the presence of phagocytes in the
      wound. The analysis of the wound by optical and electron microscopy did not
      detect cells with morphological characteristics of phagocytes in it. The wound is
      completely covered by the external cuticle of the animal 24 hr after the lesion
      was made. A second section of the animal leads to abnormal healing of the lesion.
      The insertion of a surgical silk thread in the muscle of the animals results-
      after 13 days--in a collection of cells surrounding the foreign body. The
      ultrastructural analysis of these cells showed they are endothelial cells rather
      than specialized phagocytes. Yet, the Amphioxus is able to mount an allograph
      rejection when the animals are tied together by suture. This intriguing capacity
      of the Amphioxus to cope with tissue healing, infection, and other pathologies
      without phagocytes is discussed.

PMID- 7722342
TI  - The insecticidal CryIB crystal protein of Bacillus thuringiensis ssp.
      thuringiensis has dual specificity to coleopteran and lepidopteran larvae.
AB  - The crystals found in sporulation extracts of Bacillus thuringiensis (Berliner)
      contain proteins that are highly toxic to insects. Different crystal proteins
      exhibit distinct specificities for restricted groups of insects. An
      uncharacterized strain of B. thuringiensis (BtS2), derived from China, was found
      to carry several crystal protein genes and to be toxic to a wide variety of
      insects, including some coleopterans. Surprisingly, the coleopteran toxicity was
      traced to a CryIB-class protein. The previously cloned CryIB protein from B.
      thuringiensis ssp. thuringiensis strain HD-290-I, which was believed to be
      lepidopteran-specific, was also found to be toxic to at least two species of
      coleopteran larvae under certain conditions. In contrast to CryIB toxicity toward
      lepidopterans, the coleopteran activity of CryIB is enhanced by solubilization
      and by truncation with trypsin prior to administration. The magnitude of this
      effect varies with the host species and is reversed for the one lepidopteran
      tested. These results suggest that, for at least some insects, the apparent host
      specificity of CryIB may depend both on differences in midgut environment and on
      differences in toxin-receptor interaction. The results of insect toxicity
      experiments with a series of deletion mutants allowed definition of a CryIB
      protein fragment of ca. 65 kDa as the smallest peptide that retains bioactivity
      against both lepidopteran and coleopteran larvae. Deletions smaller than this
      resulted in the production of a protein that was nontoxic to both lepidopteran
      and coleopteran larvae.

PMID- 7722343
TI  - Viral particles in a flatworm (Paravortex tapetis) parasitic in the commercial
      clam, Ruditapes decussatus.

PMID- 7722344
TI  - Issues of multiple frame averaging in quantitative coronary arteriography.

PMID- 7722345
TI  - Accuracy and precision of quantitative arteriography in the evaluation of
      coronary artery disease after coronary bypass surgery. A validation study.
AB  - Computer-assisted quantitative coronary arteriography (QCA) has gained widespread
      acceptance in assessing changes in coronary dimensions over time, but little is
      known about the utility of QCA in patients having undergone coronary bypass
      surgery. As a validation study, we analyzed the accuracy and precision of QCA in
      a subset of the baseline angiograms of a clinical trial in 395 post-bypass men
      with low HDL cholesterol concentrations who have been randomized to receive
      double-blind gemfibrozil or placebo for 2 1/2 years. Based on repeat measurements
      of the same cineframe, the average diameter of a segment (ADS) had a mean
      coefficient of variation (CV) of 3.1%. The mean CVs of the minimum luminal
      diameter (MLD), percent diameter stenosis (PDS) and stenotic flow reserve of an
      obstruction were 8.6, 10.2 and 9.8%, respectively, but the area of the
      atherosclerotic plaque had an unacceptably high CV, 24.0%. When the measurements
      from two contrast injections into a native coronary artery during the same
      angiographic session were compared, precision (standard deviation of the
      differences) was 0.198 mm for ADS, 0.192 mm for MLD, and 7.37% for PDS.
      Variability was not substantially reduced when measurements from 3 or 5
      consecutive cineframes were averaged. Comparable repeatability was found when
      venous bypass grafts were imaged twice, whether the grafts themselves or the
      grafted native vessels were analyzed. We conclude that QCA has an acceptable
      accuracy and precision in analyzing coronary dimensions in bypass-grafted
      patients. A change of 0.40 mm in ADS and MLD, and 20% in PDS represent true
      progression or regression of coronary atherosclerosis with more than 95%
      confidence.

PMID- 7722346
TI  - A new method for automatic identification of coronary arteries in standard
      biplane angiograms.
AB  - A new computerized method for analyzing biplane coronary arteriograms was
      proposed. The method extracted the vessels in an image, detected branching
      points, and identified vessel segments according to their anatomical names. The
      method was applied to a pair of orthogonal projection images acquired in the
      right anterior oblique and left anterior oblique views. It recognized the
      corresponding vessel segments in the images and labeled them correctly by their
      anatomical names. For diameter measurement, a combined first and second
      derivative filter process was applied to the images along the skeleton lines of
      the extracted vessel segments. We also designed a method of representation in
      which vessel diameters measured in the two projection images could be displayed
      in a single image.

PMID- 7722347
TI  - Left atrial-volume determination by echocardiography. Validation by biplane
      angiography in the setting of mitral balloon valvuloplasty.
AB  - To validate echocardiographic left atrial volume measurements, 25 patients with
      mitral stenosis were studied before and after mitral balloon valvuloplasty. Seven
      normals served as controls. The modified Simpson's rule was used for
      echocardiographic and angiographic left atrial volume determination from two
      orthogonal planes. Left atrial antero-posterior diameter was measured from
      parasternal long axis view and supero-inferior and medio-lateral diameters from
      apical four-chamber view. Transthoracic echocardiographic left atrial volume
      correlated well, but systematically underestimated angiographic left atrial
      volume (y = 0.4x + 27, r = 0.92). Monoplane transesophageal echocardiography did
      not improve correlation, nor the underestimation. Out of the several left atrial
      diameters, antero-posterior dimension showed the closest correlation with
      angiographic volume (r = 0.91), which persisted after exclusion of patients with
      atria > 400 ml (r = 0.84). Furthermore, relative changes of antero-posterior
      diameter after mitral valvuloplasty were closely related to the relative changes
      observed in left atrial volume (r = 0.82). Our results suggest that, in spite of
      a consistent underestimation, bidimensional, transthoracic echocardiographic and
      angiographic left atrial assessment correlate closely. Moreover, it is suggested
      that the mere antero-posterior diameter from transthoracic two-dimensional image
      is sufficient in clinical practice for routine follow-op of left atrial volume.

PMID- 7722348
TI  - Detection of early systolic dysfunction in ischemia by sequential radionuclide
      imaging of ejection rates.
AB  - The effectiveness of sequential imaging of early regional left ventricular
      contraction in the detection of ischemic abnormalities was assessed in 47
      patients (15 with previous infarction) with angiographically proven coronary
      artery disease, and 11 normal volunteers, undergoing first pass radionuclide
      angiography with a multielement gamma camera at rest and at peak exercise. Global
      left ventricular hemodynamic parameters, and functional images of regional
      ejection fraction and ejection rate were compared to 6 pairs of sequential rate
      images showing the decrease and the increase of regional left ventricular volume
      during a time-interval of 80-280 ms (at rest) and 50-175 ms (at stress) from end
      diastole. Diagnostic accuracy of sequential images (67-91%) was higher than that
      of ejection rate image (71-72%), and of global hemodynamic parameters (33-60%),
      in the detection of coronary patients. Regional sensitivity of stress sequential
      increase and decrease image achieved 77% and 100%, respectively. During early
      systole sensitivity of stress sequential increase and decrease images approached
      100% even at rest, subsequently decreasing because of normalizing contraction.
      Thus, the analysis of early systolic dysfunction provided by dynamic sequential
      functional images of ejection rates proved to be an effective diagnostic tool in
      the detection of myocardial ischemic dysfunction.

PMID- 7722349
TI  - Visual assessment of intra ventricular flow from colour M-mode Doppler images.
AB  - Left intra ventricular filling was studied by colour M-mode Doppler ultrasound to
      determine whether the flow pattern can be assessed visually, and explore its
      relation to left ventricular (LV) function. Patients with coronary artery disease
      (CAD) or dilated cardiomyopathy (DCM) were divided into three groups according to
      angiographically evaluated LV function. The groups were compared with a control
      group of 54 healthy volunteers. The mitral to apical delay of early diastolic
      flow was qualitatively assessed from printed colour M-mode images, twice by four
      independent observers blinded to the subject's status. The repeatability of the
      assessments as determined by the kappa statistic was good intra observer (kappa =
      0.75) and moderate inter observer (kappa = 0.53). The CAD-group with
      angiographically normal LV function (n = 25) had flow patterns resembling those
      observed in the control group. The group with ejection fraction (EF) < 50% (n =
      19) had flow patterns clearly different from the control group. Patients with
      regional wall motion abnormality (RWMA) but EF > 50% (n = 16) exhibited flow
      patterns intermediate between the control and the low EF group. Among the 50 CAD
      patients there was a negative correlation between EF and the presence of delay of
      apical peak velocity (Spearman's rs = -0.62, p < 0.0001). A visible delay of
      apical peak velocity had a sensitivity towards DCM of 83% and specificity of 75%.
      The sensitivity towards CAD with either RWMA or low EF was 55% and the
      specificity 75%. In conclusion, visual assessment of intra ventricular flow
      patterns was feasible and allowed discrimination between normal and diseased
      ventricles.

PMID- 7722350
TI  - Left and right heart Doppler stress echo in congestive heart failure.
AB  - Doppler echocardiographic assessment of the left and right ventricular function
      at rest, during and 6 minutes after submaximal exercise was performed in 60
      patients with a mean age of 43 +/- 11 years suffering from heart failure
      classified stage I-III according to the NYHA-criteria and 10 volunteers with a
      mean age of 36 +/- 9 years who served as a control group. At mitral (m) and
      tricuspid (t) valve early diastolic peak-flow velocity (VEm, VEt), atrial peak
      flow velocity (VAm, VAt), speed-time integrals (Em, Et, Am, At) and the ratios
      (VE/VAm, VE/VAt, E/Am, E/At) were determined. The left ventricular end-diastolic
      diameter (LVEDD) and the right ventricular outflow tract (RVOT) were measured in
      addition. The left ventricular ejection fraction (LVEF) was decreased to < 36% in
      9 patients (group 1). In 51 individuals LVEF was found to be > 35% but < 50% or
      LVEF was shown to be > 50% but VE/VAm-ratio was found to be < 1 (group 2). Out of
      all the determined parameters, VE/VAt, VEt and VAm during exercise were found to
      be the most sensitive parameters for the detection of early to advanced grade
      left heart failure.

PMID- 7722351
TI  - Left ventricular function in asthmatic children chronically treated with
      theophylline evaluated by exercise Doppler echocardiography.
AB  - To evaluate the chronic effects of theophylline on cardiac function, M-mode and
      pulsed Doppler derived variables were measured at rest and the suprasternal
      continuous wave Doppler measurement of ascending aortic flow was used during
      treadmill exercise testing. Subjects consisted of 13 children with stable asthma
      (mean 11.7 +/- 2.2 years) who were treated with theophylline for at least one
      year and 16 age-matched, untreated normal volunteers. In the resting state, the
      chronic administration of theophylline seemed to produce a slight increase in
      percent fractional shortening, outflow peak velocity and atrial contribution to
      ventricular filling in the asthmatic children as compared to normals, but these
      changes were not statistically significant. The asthmatic children showed
      significantly lower values than the controls in exercise induced changes in the
      peak velocity, stroke index and cardiac index, but not in the heart rate.
      Therefore, chronic administration of theophylline appears to have a minimal
      effect on resting cardiac function, but a possibly deleterious effect on the
      cardiac response to exercise testing.

PMID- 7722352
TI  - Detection of acute thrombosis of mitral tilting disk prosthesis by
      transesophageal echocardiography.
AB  - Acute thrombosis is a very severe complication in the replacement of mechanical
      prostheses and most often fatal if immediate treatment is not implemented. We
      describe a case in which an acute thrombosis of a mitral tilting disk prosthesis
      was adequately diagnosed by transesophageal echocardiography and immediate
      surgical replacement of the dysfunctioning device was possible without
      catheterizing the patient.

PMID- 7722353
TI  - [Hypertension and cancers].

PMID- 7722354
TI  - [Case of polymyositis with dilated cardiomyopathy associated with mitochondrial
      myopathies].

PMID- 7722355
TI  - [A case of quintuple primary malignant tumors].

PMID- 7722356
TI  - [A case of lithium induced sinus mode dysfunction].

PMID- 7722357
TI  - [A case of insulinoma diagnosed effectively by arterial stimulation and venous
      sampling using artificial islets of Langerhans].

PMID- 7722358
TI  - [A case of primary HCG-producing intracranial germinoma effectively treated by
      high-dose chemotherapy and autologous bone marrow transplantation].

PMID- 7722359
TI  - [A case of asthma associated with ancylostomiasis and pulmonary eosinophilia].

PMID- 7722360
TI  - [Diet therapy: role of incretin and dietary fibers].

PMID- 7722361
TI  - [Epidemiological changes in cerebrovascular disorders].

PMID- 7722362
TI  - [Hypertension and endothelin].

PMID- 7722363
TI  - [Hypertension and natriuretic peptide family].

PMID- 7722364
TI  - [Recent advance in genetic study of hypertension].

PMID- 7722365
TI  - [New antihypertensive agents: adrenomedullin].

PMID- 7722366
TI  - [Diagnostic criteria of hypertension].

PMID- 7722367
TI  - [Clinical evaluation of home blood pressure determination and 24-hour
      monitoring].

PMID- 7722368
TI  - [Diagnostic procedures in patients with hypertension].

PMID- 7722369
TI  - [Occurrence and etiology of secondary hypertension].

PMID- 7722370
TI  - [Limitation and effectiveness of non-drug therapy of hypertension].

PMID- 7722371
TI  - [Recent trend in drug therapy of hypertension].

PMID- 7722372
TI  - [Treatment of mild hypertension].

PMID- 7722373
TI  - [Treatment of hypertension in the elderly].

PMID- 7722374
TI  - [Hypertension and insulin resistance].

PMID- 7722375
TI  - [Prognosis of hypertension and complications].

PMID- 7722376
TI  - [Diagnosis and therapy of hypertension in the elderly. Discussion].

PMID- 7722377
TI  - [Important points in early diagnosis of drug-induced lesions of the digestive
      system].

PMID- 7722378
TI  - [Recent trends of drug-induced liver diseases].

PMID- 7722379
TI  - [Pathological differences between drug-induced and viral liver diseases].

PMID- 7722380
TI  - [Etiological mechanism of toxic hepatitis].

PMID- 7722381
TI  - [Etiological mechanism of drug-allergy liver disease].

PMID- 7722382
TI  - [Approach to diagnosis of drug-induced liver diseases].

PMID- 7722383
TI  - [Differences in clinical findings between drug-induced and viral liver diseases].

PMID- 7722384
TI  - [Various problems in therapy and prognosis of drug-induced liver diseases].

PMID- 7722385
TI  - [Etiology, physiopathology and therapy of drug-induced gallbladder lesions].

PMID- 7722386
TI  - [Drugs-induced and etiological mechanism of pancreatitis].

PMID- 7722387
TI  - [Various problems in physiopathology, therapy and prognosis of drug-induced
      pancreatitis].

PMID- 7722388
TI  - [Etiological mechanism and drug-induced gastric mucosal lesions].

PMID- 7722389
TI  - [Physiopathology and therapy of drug-induced stomach diseases in the aged].

PMID- 7722390
TI  - [Etiological mechanism of drug-induced intestinal diseases].

PMID- 7722391
TI  - [Physiopathology and therapy of drug-induced intestinal diseases].

PMID- 7722392
TI  - [Drug-induced digestive system diseases. Discussion].

PMID- 7722393
TI  - [A case of minocycline-induced pulmonary eosinophilia with no abnormal thoracic
      radiography findings diagnosed by Ga scintigraphy].

PMID- 7722394
TI  - [A case of acute fulminant myocarditis associated with Guillain-Barre syndrome].

PMID- 7722395
TI  - [Differential diagnosis of a case of adult-onset Still's disease from bacterial
      meningitis].

PMID- 7722396
TI  - [A case of Laurence-Moon-Biedle syndrome associated with renal tubular acidosis
      and kidney dysfunction].

PMID- 7722397
TI  - [A case of toxocara canis infection].

PMID- 7722398
TI  - [A case of ischemic colitis due to an oral contraceptive agent].

PMID- 7722399
TI  - [A case of acute pancreatitis with portal-vein thrombosis].

PMID- 7722400
TI  - [Respiratory system diseases and cytokines].

PMID- 7722401
TI  - [Diet therapy of early-stage kidney failure].

PMID- 7722402
TI  - Doctors can get it, too. Preventing the transmission of Mycobacterium
      tuberculosis in health care settings.

PMID- 7722403
TI  - Gynecological surgical outcomes among asymptomatic human immunodeficiency virus
      infected women and uninfected control subjects.
AB  - To determine the effect of asymptomatic human immunodeficiency virus (HIV)
      infection on the risk of complications and outcomes in women undergoing
      gynecological surgical procedures, retrospective analysis was performed of 62
      asymptomatic HIV-infected women who underwent gynecological procedures. One
      hundred forty seronegative women who had similar procedures during the same time
      period served as controls. Procedures included tubal sterilization, hysterectomy,
      and diagnostic laparotomy. The following variables were compared: length of
      hospital stay, age, blood loss, white blood cell count, hemoglobin, and
      hematocrit. Laboratory parameters were compared pre-and postoperatively, as well
      as between the study and control groups. Race and parity were similar in both
      groups. HIV-infected women were younger (mean: 25 years versus 31 years) than
      controls. Length of hospital stay was similar. Blood loss was higher in the HIV
      infected group than controls. (318 cc versus 122 cc) Differences in white blood
      cell counts, hematocrits, and febrile morbidity were insignificant. Asymptomatic
      HIV infection has minimal effect on the outcome of elective gynecologic surgery.
      The younger age of the HIV-infected women reflects the demographics of HIV
      infection and sterilization reflects the desire to prevent perinatal
      transmission.

PMID- 7722404
TI  - ECG of the month. True or false? Pseudoarrhythmia.

PMID- 7722405
TI  - Barotrauma.

PMID- 7722406
TI  - Medical/legal interprofessional code.

PMID- 7722407
TI  - A 69-year-old man with pulmonary infiltrates and glomerulonephritis.
AB  - The differential diagnosis for a 69-year-old man with pulmonary nodules and
      glomerulonephritis is discussed in the setting of a Clinicopathological
      Conference at Louisiana State University Medical Center in Shreveport, Louisiana.
      The pathophysiology and etiology of pulmonary-renal syndromes are discussed.

PMID- 7722408
TI  - The role of the innate immune response in Th1 cell development following
      Leishmania major infection.
AB  - Infection of mice with the protozoan parasite Leishmania major is an established
      model with which to study the in vivo development of CD4+ Th cell subsets.
      Interferon-gamma (IFN-gamma), produced by natural killer (NK) cells (AsGM1+, CD4
      , CD8-, CD3-), regulates CD4+ T cell subset development and early resistance to
      L. major. Rapid Th1 cell development and resistance to infection occur in mice
      that develop an NK cell response early after infection (C3H and immunized BALB/c
      mice), whereas mice that lack an early NK cell response demonstrate delayed Th1
      cell development and enhanced early disease (C57BL/6) or lack detectable Th1 cell
      development altogether and develop a progressive, fatal infection (BALB/c).
      Analysis of the requirements for NK cell activation in C3H mice revealed that the
      NK cell response is both interleukin-2 (IL-2) and IL-12 dependent. Although
      delayed IL-12 production in C57BL/6 mice precludes NK cell activation, the
      eventual development of a Th1 response appears to be IL-12 dependent. In
      contrast, concomitant production of inhibitory factors (IL-4, IL-10, and
      transforming growth factor beta) with IL-12 and IL-2 prevents NK cell activation
      in BALB/c mice. Together, these observations support a paradigm of in vivo Th1
      cell development that involves IL-12-dependent stimulation of IFN-gamma
      production by NK cells.

PMID- 7722409
TI  - The role of PECAM-1 (CD31) in leukocyte emigration: studies in vitro and in vivo.
AB  - Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a molecule
      capable of mediating both homophilic and heterophilic adhesion. It is
      constitutively expressed and concentrated in the lateral borders between
      endothelial cells and expressed on the surfaces of neutrophils, monocytes, and
      some T cell subsets, as well as on platelets. In a quantitative in vitro assay,
      monoclonal antibody against PECAM-1 or soluble recombinant PECAM-1 selectively
      blocked passage of both neutrophils and monocytes across the endothelial
      monolayer by 70-90% without interfering with the ability of these cells to bind
      to the apical endothelial cell surface. These regents worked whether directed
      against leukocyte PECAM-1 or against endothelial cell PECAM-1 and were not
      additive, suggesting that a homophilic interaction was occurring. In a murine
      model of acute inflammation, thioglycollate-induced peritonitis, a monoclonal
      antibody against mouse PECAM-1 blocked emigration of leukocytes into the
      peritoneal cavity down to background levels. Examination of peritoneal venules in
      these mice revealed many leukocytes in apparent contact with the endothelial
      surface but unable to cross the intima. Thus, PECAM-1 has a distinct role in the
      transendothelial migration phase of leukocyte emigration, independent of the
      adhesion events on the apical surface.

PMID- 7722410
TI  - A direct signaling pathway through tyrosine kinase activation of SH2 domain
      containing transcription factors.
AB  - Studies on the mechanism of interferon-induced gene expression revealed a direct
      signaling pathway from cell surface receptors to transcription factors. In this
      pathway, signal transduction is mediated by a new class of transcription factor
      STAT (signal transducer and activator of transcription). We have shown that STAT
      factors contain Src homology region 2 and 3 domains and are phosporylated and
      activated in the cytoplasm by receptor associated tyrosine kinases. The activated
      transcription factors then translocate to the nucleus, joined by a nuclear DNA
      binding factor, to form an active transcriptional complex. Recent studies have
      shown that this direct signaling pathway is the key to control of gene expression
      induced by many cytokines and growth factors.

PMID- 7722411
TI  - NFATp, a cyclosporin-sensitive transcription factor implicated in cytokine gene
      induction.
AB  - The transcription factor NFATp (nuclear factor of activated T cells, preexisting)
      is likely to regulate the cyclosporin-sensitive transcription of cytokine genes
      and other activation-associated genes during the immune response. NFATp is the
      first identified member of a new family of transcription factors, whose DNA
      binding domains show a weak sequence similarity to those of the Rel (NF-kappa B)
      family of proteins. NFATp is expressed in several types of immune cells as a
      cytosolic protein that translocates to the nucleus following activation. The
      nuclear translocation is regulated by calcium and calcineurin and inhibited by
      cyclosporin A and FK506. In the nucleus, NFATp cooperates with Fos-Jun dimers and
      possibly with other transcription factors at composite elements in the regulatory
      regions of cytokine genes. The potential roles of NFATp and a related family
      member, NFATc, in cytokine gene transcription are discussed.

PMID- 7722412
TI  - Pathways for the processing and presentation of antigens to T cells.
AB  - Two pathways exist within vertebrate cells to generate peptides for recognition
      by T cells. The "endogenous" pathway provides peptides to MHC class I molecules
      for presentation to CD8+ T cells. These peptides are derived from proteins
      synthesized or residing in the cytoplasm or nucleus, and involves proteasomes and
      the ubiquitin pathway of protein degradation, as well as a specific peptide
      transporter (TAP) that allows these peptides access to the lumen of the
      endoplasmic reticulum. The exogenous pathway provides peptides to MHC class II
      molecules for presentation to CD4+ T cells. These peptides are derived from
      extracellular antigens taken up by endocytosis and degraded in the
      endosomal/lysosomal pathway. Peptide loading of MHC class II molecules requires
      the presence of a molecule (H-2M in mouse, HLA-DM in humans) that is structurally
      related to MHC class II molecules, but the mechanistic basis of this requirement
      is unknown. The class II region of the MHC contains a cluster of genes encoding
      proteins involved in antigen processing, including genes for two proteasome
      subunits (LMP2 and LMP7), the peptide transporter heterodimer (TAP1 and TAP2),
      and the H-2M/HLA-DM molecule (Ma and Mb, or DMA and DMB).

PMID- 7722413
TI  - Functional significance of two cytolytic pathways of cytotoxic T lymphocytes.
AB  - Cytotoxic lymphocytes are equipped with several effector molecules mediating
      cytotoxicity. Two pathways have been molecularly defined and functionally
      characterized through the analysis of deficiency states. It is evident from these
      results that lysis by granule exocytosis serves primarily to eliminate exogenous
      and endogenous hazards such as virally infected and transformed cells. In
      contrast, lysis by induced suicide in the fas pathway is used to maintain
      homeostasis of rapidly expanding and contracting cell populations including T
      cells.

PMID- 7722414
TI  - CD11/CD18-independent transendothelial migration of human polymorphonuclear
      leukocytes and monocytes: involvement of distinct and unique mechanisms.
AB  - Monocytes and polymorphonuclear leukocytes (PMNLs) migrate across cytokine
      (interleukin-1, tumor necrosis factor) activated endothelium or unstimulated
      endothelium in response to chemotactic factors in vitro and in vivo utilizing the
      CD11/CD18 (i.e., beta 2 integrin) adhesion molecule complex. However, in vivo
      studies have suggested that under some conditions and/or in certain tissues,
      leukocyte migration can also proceed via CD11/CD18-independent mechanisms. Here
      we compared adhesion mechanisms involved in the migration of 51Cr-labeled blood
      monocytes and PMNLs across human umbilical vein endothelium (HUVE) monolayers. We
      observed that monocyte transendothelial migration was not inhibited by monoclonal
      antibody (mAb) to CD18, when the HUVE was activated with IL-1 and the chemotactic
      factor C5a induced the migration. This CD18-independent monocyte migration was
      blocked by treatment of the monocyte with mAb to beta 1 or alpha 4 integrin,
      suggesting that very late activation antigen 4 (VLA-4) on the monocyte served as
      the alternative migration mechanism. In contrast to monocytes, mAb to CD18
      inhibited PMNL migration to C5a across IL-1-activated HUVE, but only by 66%,
      significantly less than with C5a alone (84%) or IL-1-activated HUVE alone (95%).
      The migration of anti-CD18 mAb-treated PMNLs was not inhibited by function
      blocking mAbs to sialyl Lewisx, L-selectin, beta 1 or alpha 4 integrin, the beta
      3-related leukocyte response integrin, IL-8, or platelet-activating factor (PAF)
      antagonists, alone or in combination. Antibody-blocking studies of the ligands on
      HUVE indicated that E-selectin may be partially involved in this CD18-independent
      PMNL migration but that ICAM-1, VCAM-1, PECAM-1, and P-selectin are not involved.
      Of several chemotactic factors tested, C5a and C5adesArg in activated plasma were
      the most active in inducing CD18-independent migration of PMNLs across IL-1
      activated HUVE. These results demonstrate that (1) monocytes can utilize VLA-4
      for optimal transendothelial migration and (2) PMNLs may have a novel CD18
      independent migration mechanism that is activated by C5a in conjunction with one
      or more ligands on cytokine-activated endothelium. This may involve, in part, E
      selectin interacting with a yet to be identified counterreceptor on PMNLs.

PMID- 7722415
TI  - Phenotypic and functional heterogeneity of the murine alveolar macrophage-derived
      cell line MH-S.
AB  - We have previously reported that MH-S, an established murine alveolar macrophage
      derived cell line, mediated profound inhibition of in vitro antibody production,
      as did their freshly isolated alveolar macrophage (AM) counterparts. In this
      communication we show that like freshly recovered AMs, the MH-S cell line also
      displays phenotypic and functional heterogeneity. Sorting of parental MH-S cells
      by flow cytometry based on reactivity with anti-Mac-1 antibody yielded two
      subsets. Further analysis by staining with monoclonal antibodies against well
      characterized murine macrophage cell surface markers revealed that both Mac-1+
      and Mac-1- subsets expressed the mature murine macrophage antigen (F4/80) and
      class II major histocompatibility complex molecules, but with different
      intensity. In contrast, the two subsets stained equivalently with antibody
      against the Fc gamma II receptor, whereas neither subset stained with anti-CD4
      antibody. Examination by light microscopy revealed plemorphism in the Mac-1+
      population with many of the cells appearing spindle shaped and having elongated
      processes, whereas a majority of the cells in the Mac-1- population were
      spherical in shape. Functionally, cells from the Mac-1+ population were less
      inhibitory of in vitro antibody production and produced significantly more nitric
      oxide in response to stimulation with lipopolysaccharide than were cells in the
      Mac-1- population. Essentially similar results were obtained using cloned Mac-1+
      and Mac-1- MH-S cells. The finding of heterogeneity in an established cell line
      that displays functions similar to those of freshly recovered AMs suggests that
      distinct subsets of AMs may be involved in the pathogenesis of disease processes
      in the lung.

PMID- 7722416
TI  - Induction of macrophage binding to virally infected cells by low levels of
      lipopolysaccharide.
AB  - Bone marrow culture-derived macrophages (BMCM) and vesicular stomatitis virus
      infected BALB/c-3T3 cells (3T3-VSV) were used to determine whether macrophages
      could be activated to bind virally infected cells. Although lipopolysaccharide
      (LPS)-activated BMCM bound some uninfected BALB/c-3T3 cells, the number of
      targets that were bound increased with increasing times between infection and
      assay. Furthermore, LPS-activated BMCM bound more 3T3-VSV cells than did control
      macrophages. As more targets were added, the number of targets bound by the
      unactivated macrophages remained relatively level. However, the number of targets
      bound by the activated macrophages increased with increasing concentrations of
      added targets until they reached a plateau that was eight times greater than that
      bound by the unactivated BMCM. When BMCM were exposed to LPS for 24 h before
      assay, they lost both their ability to bind to 3T3-VSV and their cytolytic
      activity against those targets. However, as when using P815, a standard tumor
      target, the acquisition of binding of 3T3-VSV could be separated from macrophage
      cytolytic activity against those targets. The amount of LPS required to activated
      BMCM for increased binding of 3T3-VSV cells was 10-100 times lower than that
      needed to induce cytolytic activity for 3T3-VSV cells. Each of these values was
      approximately 100-fold lower than the amount of LPS required to induce the
      corresponding activity (binding or cytotoxicity) by using P815 targets.

PMID- 7722417
TI  - Intracellular multiplication of Legionella pneumophila in HL-60 cells
      functionally differentiated in response to 22-oxacalcitriol.
AB  - The agent 1,25-dihydroxyvitamin D3 (D3) induces the differentiation of HL-60
      human leukemia cells into functional monocyte-like cells that can support the
      intracellular multiplication of Legionella pneumophila. 22-Oxacalcitriol (OCT), a
      synthetic analogue of D3, exhibits greater differentiation-inducing activity than
      D3 in WEHI-3 mouse leukemia cells and has been suggested to be clinically more
      useful because of its lower hypercalcemic activity. The abilities of OCT and D3
      to induce the functional differentiation of human leukemia HL-60 cells have now
      been investigated. OCT induced the differentiation of HL-60 cells into monocyte
      like cells to a similar extent as D3. Thus, both OCT and D3 increased (1) the
      surface expression of CD11b, CD11c, CD14, and CD35; (2) nonspecific esterase
      staining; and (3) phagocytic activity toward fluorescent beads. HL-60 cells
      differentiated in response to OCT also supported the intracellular multiplication
      of L. pneumophila. Activation of both OCT- and D3-treated HL-60 cells with human
      recombinant interferon-gamma (IFN-gamma) for 24 h before infection markedly
      inhibited L. pneumophila multiplication. IFN-gamma activation enhanced superoxide
      anion generation by D3-treated HL-60 cells but not by OCT-treated HL-60 cells,
      suggesting that the inhibition of L. pneumophila multiplication in IFN-gamma
      activated cells is independent of superoxide generation. Finally, D3, but not
      OCT, markedly stimulated the formation of osteoclast-like multinucleated cells
      from mouse bone marrow cells, consistent with the lower hypercalcemic activity of
      OCT.

PMID- 7722418
TI  - Effects of myristate phorbol ester on V-ATPase activity and Na(+)-H+ exchange in
      alveolar macrophages.
AB  - The roles of protein kinase C (PKC) in regulation of the plasmalemmal vacuolar
      type H(+)-ATPase (V-ATPase) and Na(+)-H+ exchanger (NHE) of rabbit alveolar
      macrophages (m phi) were investigated using phorbol 12-myristate 13-acetate
      (PMA). At an extracellular pH (pHo) of 7.4 (nominal absence of CO2-HCO3-), PMA
      caused a dose-dependent increase in the rate of cellular H+ extrusion with little
      change in intracellular pH (pHi). PMA caused a prolonged cytosolic acidification
      at pHo < or = 6.8. PMA-induced changes in pHi were sensitive to bafilomycin A1,
      but were insensitive to amiloride. Studies of pHi recovery following
      intracellular acid challenge showed that both V-ATPase and the NHE were up
      regulated by PMA. An inactive analog, 4 alpha-phorbol, had no detectable effects
      on pHi homeostasis. These data indicate that (a) PKC is involved in regulation of
      V-ATPase and the NHE of resident alveolar m phi and (b) V-ATPase is the
      predominant mechanism for pHi homeostasis in unstimulated and PMA-activated m
      phi.

PMID- 7722419
TI  - Na(+)-H+ exchange in resident alveolar macrophages: activation by osmotic cell
      shrinkage.
AB  - Intracellular pH (pHi) homeostasis in resident alveolar macrophages (m phi) under
      nominally CO2-free conditions is mediated primarily by the activity of
      plasmalemmal H(+)-ATPase. The m phi also possess an Na(+)-H+ exchanger (NHE) but
      this mechanism has no detectable role in pHi regulation in the physiologic range.
      To further explore the physiological significance of the NHE in this cell type,
      resident alveolar m phi from rabbits were subjected to a hyperosmotic challenge
      (approximately 620 mOsm/kg) in the nominal absence of CO2-HCO3-. Osmotic cell
      shrinkage was accompanied by an amiloride-sensitive increase in baseline pHi. The
      NHE-mediated rate of pHi recovery from intracellular acid loads also increased
      under hyperosmotic conditions. Cell shrinkage caused an alkaline shift in the pHi
      set point of the NHE without altering the exchanger's affinity for extracellular
      Na+. The results indicate that Na(+)-H+ exchange in resident alveolar m phi is
      activated by osmotic cell shrinkage and imply that the NHE may be involved in
      volume regulatory responses of the cell.

PMID- 7722420
TI  - Effects of endotoxin on expression of VLA integrins by human bronchoalveolar
      lavage macrophages.
AB  - Endotoxin (lipopolysaccharide, LPS) is known to induce inflammatory responses,
      such as monocyte/macrophage adherence, migration, and accumulation. Recruitment
      and accumulation of macrophages during infection and inflammation are regulated
      by integrin-mediated cell-extracellular matrix interactions. In the present
      report, we studied the effects of LPS on the expression of VLA-5 (alpha 5 beta
      1), VLA-3 (alpha 3 beta 1), and VLA-2 (alpha 2 beta 1) integrins and fibronectin
      (FN) by human alveolar macrophages in an attempt to understand the mechanism by
      which LPS regulates macrophage adhesion to matrix proteins. Bronchoalveolar
      lavage macrophages were treated with varying concentrations of Escherichia coli
      LPS for different times and evaluated for expression of the integrins and FN by
      immunofluorescence, immunoelectron microscopy, autoradiography, and
      radioimmunoassay. Immunofluorescent and immunoelectron microscopic observations
      showed that VLA integrins were constitutively expressed on the cell surface and
      concentrated on the microvilli and pseudopodia of the macrophages. The effects of
      LPS on expression of the integrins were dose and time related. VLA-5 expression
      was increased after 30 min of stimulation by LPS, suggesting that LPS may induce
      rapid secretion of the integrin. However, incubations with LPS longer than 30 min
      decreased VLA-5 expression in a dose-dependent pattern. LPS also caused dose
      related decreases in the expression of VLA-3 and VLA-2 integrins and increases of
      intracellular FN 24 h after stimulation. The results suggest that a prolonged
      exposure to LPS may impede VLA integrin-mediated migration and result in local
      accumulation of macrophages in the lung.

PMID- 7722421
TI  - T cells and HIV-induced T cell syncytia exhibit the same motility cycle.
AB  - Ameboid cells ranging in complexity from Dictyostelium amebas to human
      polymorphonuclear leukocytes (PMNs) translocate in a cyclical fashion. Using
      computer-assisted motion analysis, we have analyzed the motility of human
      lymphocytes of the immortal SupT1 cell line and of a peripheral blood mononuclear
      cell population highly enriched for CD4-positive cells (CD4-enriched PBMCs) on
      four substrates--plastic, dehydrated rat tail collagen, hydrated rat tail
      collagen, and bovine aortic endothelium. In addition, we have analyzed the
      motility on these substrates of syncytia induced by human immunodeficiency virus
      (HIV) in cultures of both cell types. It is demonstrated that both SupT1 cells
      and CD4-enriched PBMCs exhibit a motility cycle with a period of 1.6 min that is
      independent of substrate, independent of average cell velocity, and similar to
      the periods of translocating Dictyostelium amebas and PMNs. More surprisingly, it
      is demonstrated that HIV-induced SupT1 and PBMC syncytia with volumes 10 to 100
      times those of single cells exhibit the same motility cycle as their single-cell
      progenitors. These observations support the generality of the motility cycle in
      animal cells and, for the first time, demonstrate that the cycle is independent
      of cell size.

PMID- 7722422
TI  - Immune complexes increase nitric oxide production by interferon-gamma- stimulated
      murine macrophage-like J774.16 cells.
AB  - Murine macrophage-like J774.16 cells were tested for changes in nitric oxide
      production upon incubation with immune complexes. Cryptococcus neoformans
      capsular polysaccharide and polysaccharide-specific monoclonal antibodies were
      added to J774.16 cells in the presence and absence of recombinant murine
      interferon-gamma (IFN-gamma). The effect of immune complexes on nitrite synthesis
      was both concentration dependent and isotype dependent. In the presence of IFN
      gamma, immune complexes of IgG1, IgG2, IgG2b, or IgG3 isotype increased nitrite
      levels, whereas complexes of IgM isotype did not. Immune complexes did not alter
      nitrite production by unstimulated macrophages. Antibody alone, antigen alone,
      and antigen with irrelevant IgG1 antibody did not augment nitrite formation,
      either in the presence or absence of IFN-gamma, indicating a requirement for Fc
      gamma R cross-linking. These results suggest that IgG isotypes may offer
      additional protection against pathogens by enhancing macrophage nitric oxide
      production.

PMID- 7722423
TI  - IFN-gamma increases cathepsin H mRNA levels in mouse macrophages.
AB  - Expression of major histocompatibility complex (MHC) class II molecules and
      ability to present antigen to T lymphocytes is acquired upon activation of the
      macrophage by interferon-gamma (IFN-gamma). Little information is available
      concerning immune regulation of protease gene expression in mouse macrophages. We
      have isolated a cDNA clone for cathepsin H, a lysosomal cysteine proteinase from
      a cDNA subtraction library of mouse macrophage genes induced by IFN-gamma, and
      have characterized its expression. The level of cathepsin H mRNA increased in
      mouse peritoneal macrophages following addition of IFN-gamma. Cathepsin H mRNA
      levels began to increase 8 h after the addition of IFN-gamma and was maximal at
      24-48 h. This increase was concordant in time with appearance of MHC class II E
      beta mRNA and Ia invariant chain mRNA. The increase in cathepsin H mRNA levels by
      IFN-gamma was dose dependent. Cycloheximide treatment of peritoneal macrophages
      inhibited the increase in cathepsin H mRNA levels induced by IFN-gamma,
      suggesting that the increase in cathepsin mRNA levels requires de novo protein
      synthesis. Lipopolysaccharide and cytokines interleukin-2 (IL-2), IL-4, IL-10,
      and tumor necrosis factor alpha were found to have no effect on cathepsin H mRNA
      levels in mouse peritoneal macrophages.

PMID- 7722424
TI  - Localization of cyclic GMP-dependent protein kinase in human mononuclear
      phagocytes.
AB  - The presence and physiological role of cGMP-dependent protein kinase (G-kinase)
      was investigated in human mononuclear phagocytes. Western blots of monocyte
      extracts revealed a single polypeptide band that comigrated with purified bovine
      lung G-kinase. G-kinase was localized by immunofluorescence microscopy in freshly
      isolated adherent human monocytes, monocyte-derived macrophages cultured from 4
      to 14 days, and alveolar macrophages. In monocytes, G-kinase was localized in
      granules or vesicles in the cytoplasm, at the microtubule organizing center, on
      filaments, and in the nucleus. In monocyte-derived macrophages, intense staining
      for G-kinase was found in the vicinity of the Golgi, in vesicles throughout the
      cytoplasm, and diffusely in the nucleus. Dual-label confocal laser scanning
      microscopy demonstrated that G-kinase was colocalized with the endoplasmic
      reticulum. For comparison, G-kinase was localized in alveolar macrophages that
      were adhered from 3 to 30 min. In these cells, G-kinase was prominent within the
      organelle-rich area pericortical to the nucleus. However, a well-defined area of
      intense staining was also observed at the cell periphery at early time points
      during adherence and spreading. Rhodamine-labeled phalloidin showed that this
      peripheral area was rich in F-actin. Cytochalasin D, but not nocodazole,
      inhibited G-kinase targeting to the cell margin. Furthermore, the guanylate
      cyclase inhibitor LY83583 inhibited alveolar macrophage spreading and staining
      for G-kinase at the cell periphery. These data suggest that G-kinase may play an
      important role in cGMP-mediated regulation involved in protein processing and
      cell motility.

PMID- 7722425
TI  - Chemoattractant receptor-specific differences in G protein activation rates
      regulate effector enzyme and functional responses.
AB  - The hypothesis that disparate neutrophil functional responses to various
      chemoattractants are regulated by receptor-specific rates of G protein activation
      was examined in HL-60 granulocytes. The initial rates of G protein activation and
      the affinity of receptor-stimulated G proteins for GTP gamma S in HL-60 membranes
      stimulated by fMet-Leu-Phe, C5a, and leukotriene B4 (LTB4) differed significantly
      among the chemoattractants, with a rank order of fMet-Leu-Phe > C5a > LTB4.
      Equilibrium GTP gamma S binding showed that all three chemoattractants activated
      a common pool of G proteins. Stimulation of phospholipase D activation, measured
      as phosphatidylethanol generation, and superoxide release in intact cells also
      occurred with a rank order of fMet-Leu-Phe > C5a > LTB4. On the other hand, the
      rank order of receptor affinities for ligand and of the EC50 of chemoattractant
      stimulation of GTP gamma S binding was C5a > LTB4 > fMet-Leu-Phe. C5a and LTB4
      receptor densities were similar but were less than formyl peptide receptor
      density. Graded pertussis toxin treatment proportionally reduced superoxide
      release and phospholipase D activation to all three chemoattractants. The results
      suggest that receptor-specific differences in G protein affinity for guanine
      nucleotides lead to different rates of guanine nucleotide exchange and, thereby,
      contribute to disparate effector enzyme and functional responses.

PMID- 7722426
TI  - Priming of tyrosine phosphorylation in GM-CSF-stimulated adherent neutrophils.
AB  - Adherence of human neutrophils to plastic, fibronectin, or collagen-coated
      surfaces modifies their response to several agonists including granulocyte
      macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF
      alpha), and fMet-Leu-Phe, permitting them to trigger superoxide anion (O2-)
      release, which they are unable to do as cells in suspension. Adherence of
      neutrophils causes a slight decrease in the basal level of tyrosine
      phosphorylation compared with that of suspended cells. The addition of GM-CSF,
      however, brings all proteins to a level of phosphorylation at least equal to that
      seen in suspended cells. In the case of a 130-kDa (p130) and a 42-kDa (p42)
      protein, the increase in tyrosyl phosphorylation in response to GM-CSF challenge
      is clearly larger in adherent than in suspended cells (6- and 4-fold increases
      for p130 and p42, respectively, in adherent cells vs. 1.7- and 2.1-fold in
      suspended cells). This is even more patient in the case of collagen-coated plates
      (9.4-fold increase for p42). Therefore, once neutrophils attach to surfaces, they
      become primed and respond to GM-CSF with greater potency than when they are in
      suspension. By Western blot analysis with anti-MAP kinase antibodies, we
      demonstrate that p42 is one member of the mitogen-activating protein kinase,
      namely the p42MAPK. The tyrosyl phosphorylation of p42MAPK is elevated in GM-CSF
      treated adherent neutrophils in a time-dependent fashion as measured by the
      formation of a doublet composed of the phospho (or activated) form and the
      dephospho (or inactive) form of MAP kinase. MAP kinase activation and tyrosine
      phosphorylation are inhibited by tyrosine kinase inhibitors genistein and
      tyrphostin-23. Our results indicate that adherence acts to prime neutrophils for
      enhanced functionality and that tyrosine phosphorylation is involved in this
      process.

PMID- 7722427
TI  - Electron microscopic and new microscopic studies of hepatocyte cytoskeleton:
      physiological and pathological relevance.
AB  - The cytoskeleton is involved ina wide variety of cell functions and therefore is
      implicated in the pathogenesis of various liver diseases. However, the
      relationship between localization of the cytoskeleton and hepatocyte function has
      not yet been fully elucidated. In the present study distribution of the
      cytoskeleton in relation to the physiology and pathology of hepatocytes was
      studied by electron microscopy and new microscopic techniques, including confocal
      laser scanning microscopy, time-lapse video microscopy and high sensitivity
      digital imaging microscopy. The results suggested the usefulness of the new
      microscopic techniques in the analysis of pathophysiological roles of
      cytoskeleton in the liver.

PMID- 7722428
TI  - Use of nanogold followed by silver enhancement and gold toning for preembedding
      immunolocalization in osmium-fixed, Epon-embedded tissues.
AB  - A reliable, sensitive, high-resolution method with good structural visualization
      for preembedding immunoelectron microscopy was proposed. The present technique
      involves the following processes. Immunolabeling of cryostat sections with
      primary antibodies and with nanogolds, silver intensification for visualization
      of nanogold secondary antibodies, gold-toning for stabilization of silver shells,
      and osmium postfixation and embedding in Epon for good structural visualization.
      The technique was applied to rat testis with anti-laminin and anti-fibronectin
      antibodies, showing that these two proteins are localized differentially in the
      lamina propria of the tissue.

PMID- 7722429
TI  - Experimental in vivo and in vitro formation of type VI collagen periodic fibrils
      in chorionic villi of human placenta.
AB  - The distribution of type VI collagen in the chorionic villi of normal human term
      placenta was studied. Since 100 nm periodic fibrils (type VI collagen periodic
      fibrils) are known to form in the tendon, cornea and cultured fibroblasts by
      incubation with acidic ATP solution, we incubated the placental tissue with 20 mM
      ATP, fixed it with Karnovsky's fixative and examined under an electron
      microscope. Type VI collagen periodic fibrils widely occurred in the interstitial
      connective tissue, especially close to the basal lamina. By cryo-immunoelectron
      microscopy, labeling for collagen type VI was found in the area between the
      trophoblastic basal lamina and the endothelial basal lamina. Furthermore, we
      extracted type VI collagen from the human placenta and brought both extract and
      residues into ATP treatment. Periodic structure formation was rare in extracted
      preparation compared with residues. The results served to clarify the mechanism
      of fibril formation in the tissue.

PMID- 7722430
TI  - Ultrastructural localization of intranucleolar DNA in Vicia faba root-tip cells
      by immunocytochemistry using an anti-BUdR antibody.
AB  - Ultrastructural localization of intranucleolar DNA in Vicia faba root-tip cells
      was investigated by an immunocytochemical method consisting of in vitro
      bromodeoxyuridine (BUdR)-labelling with the aid of terminal
      deoxynucleotidyltransferase and successive immunocytochemistry using an anti-BUdR
      antibody. The nucleolus usually had many low electron-opaque patches (LEPs). The
      fibrillar centers (FCs) occupied their peripheral region leaving a central
      electron-transparent space (central space). The immunoelectron microscopic
      technique showed that in the nucleolus the label was mostly confined to the FCs
      whilst the central space was completely free from the label. In other nucleolar
      regions the label appeared to gradually increase towards the FCs. In addition to
      nucleoli, this method also localized a small amount of DNA in mitochondria.

PMID- 7722431
TI  - Dynamics of hepatitis B virus core antigen in a transformed yeast cell: analysis
      with an inducible system.
AB  - Transformed yeast cells expressing hepatitis B virus core antigen (HBcAg) were
      found to accumulate abundant core particles in the same way as human hepatocytes
      infected with hepatitis B virus (HBV) by the present authors. We, therefore,
      offer a good model system for studying the dynamics of assembly of HBcAg into
      core particles. To investigate this problem, we have developed a transformed
      yeast cell in which expression of HBcAg is highly inducible by deprivation of
      phosphate in the culture medium. At regular intervals after induction, cells were
      cryo-fixed and processed for transmission electron microscopy by ultrathin
      sectioning. After induction, HBcAg activity rapidly increased, becoming several
      hundred times higher than the initial level after 25 h. The core particles first
      appeared in the nucleus, then in the cytoplasm, and finally in the vacuole. Core
      particles passing through nuclear pores from the nucleus to the cytoplasm could
      be seen. Core particles were either incorporated directly in the vacuole or
      indirectly by first forming an autophagosome. The core particles were then
      released into the vacuolar sap, and were digested there. Together with the
      previous studies, our results suggest that, in human hepatocytes, HBcAg
      polypeptides are synthesized in the cytoplasm, but are assembled into core
      particles in the nucleus. The assembled core particles are then transported from
      the nucleus to the cytoplasm through nuclear pores.

PMID- 7722432
TI  - Ultrastructural and immunocytochemical study of the subepithelial fiber component
      of the guinea pig inner ear.
AB  - The connective tissues of the lateral cochlear wall and semicircular canal of the
      guinea pig were investigated by transmission electron microscopy, intermediate
      voltage electron microscopy and immunocytochemistry. In the spiral ligament,
      numerous fibroblasts and fiber bundles were intermingled with each other.
      Fibroblasts and fibers were also observed in the semicircular canal.
      Ultrastructurally, immuno-gold particles, indicating the presence of type II
      collagen, were found on the fibers in the spiral ligament and the semicircular
      canals. The present results revealed that both stria vascularis and the
      membranous semicircular canal were supported by a network of fibroblasts and type
      II collagen fibers.

PMID- 7722433
TI  - High resolution electron microscopy of a small crack at the superficial layer of
      enamel.
AB  - A small enamel crack was investigated using a high resolution electron
      microscope. The inside of the crack was filled with aggregates of irregularly
      oriented plate-like crystals. Amorphous mineral deposits were observed among
      these aggregates at a low magnification. Selected area electron diffractions
      indicated that the plate-like crystals consisted of hydroxyapatite (OH-AP), and
      that the amorphous mineral deposits were a mixture of OH-AP and whitlockite.
      These findings indicate that this crack may have been formed by occlusal and/or
      masticatory stress, and that a natural occlusion might occur through mineral
      deposition at the small crack such as in this case.

PMID- 7722434
TI  - Proof construction: adolescent development from inductive to deductive problem
      solving strategies.
AB  - Inductive and deductive approaches to the construction of problem-solving proofs
      were examined using a task that requires the discovery of a geometrical figure
      hidden behind a series of covers. It was proposed that during adolescence, with
      the acquisition of a formal reasoning competence (as measured by Overton's [1990]
      version of Wason's selection task), there would be a transition from inductive to
      deductive proof construction strategies. One hundred adolescents were assessed on
      both the problem-solving proof task and the reasoning competence is associated
      with taking a deductive approach to proof construction. Formal reasoners tend to
      construct a proof based on the use of a falsification strategy as demonstrated by
      their search for disconfirming instances. A nonformal level of competence on the
      other hand is associated with inductive approaches. In this situation nonformal
      subjects tend to employ a verification strategy as demonstrated by the generation
      of redundant information. Results support the hypothesis that there is a
      cognitive developmental progression from an inductive approach to the
      construction of proofs to a deductive approach.

PMID- 7722435
TI  - Spatial knowledge in blind and sighted children.
AB  - Spatial knowledge was evaluated in sighted and congenitally blind children using
      a large-scale four-location navigation task adapted from the work of Landau,
      Spelke, and Gleitman (1984). From video records we coded the exact path taken and
      determined accuracy of initial turn, closest position, and final position,
      relative to target location. We then computed a score to index the efficiency of
      the path taken. For the sighted sample, after the navigation task, children
      constructed a tactile map of the test space without the aid of vision and,
      following removal of the blindfold, drew from memory the spatial layout of the
      test space. Performance on the navigation and mapping tasks consistently
      indicated increasing cognitive mapping skills with age in sighted children. Blind
      children performed comparably to the sighted on all measures except accuracy at
      final position, for which their performance was worse than that of the sighted.
      Analysis of the directness of novel paths and other measures taken suggest
      caution in ascribing well developed Euclidean coding skills to very young
      children. Results are discussed in light of Landau et al.'s (1984) conclusions.

PMID- 7722436
TI  - Effects of experience and reminding on long-term recall in infancy: remembering
      not to forget.
AB  - We examined whether some of the factors that facilitate recall in older children
      also extend to 1- to 2-years-olds. Using elicited imitation we assessed the
      efficacy of verbal (Experiment 1), and verbal plus nonverbal (Experiment 2)
      reminding on 15-month-olds' recall after a 1-week delay. Reminding ameliorated
      forgetting: Performance at delayed and immediate recall was equivalent. The
      addition of nonverbal information did not enhance recall above verbal information
      alone. In Experiment 3 we investigated the influence of verbal reminding,
      repeated experience, and mode of experience (i.e., imitate vs watch only) on
      recall after 1 month. The effects of reminding depended on event type: Reminding
      facilitated recall of events with enabling relations, but not of events lacking
      them. Repeated experience and the opportunity to imitate facilitated recall;
      children who watched events only once nevertheless recalled them. Results suggest
      that the strength of organization of an event representation, rather than
      retention interval, is a major determinant of remembering during the second year
      of life.

PMID- 7722437
TI  - Verbal and facial measures of children's emotion and empathy.
AB  - The purpose of this study was to assess the relationship between two
      theoretically distinct aspects of children's emotional responses (Lewis &
      Michalson, 1983), their emotional experience (via verbal report) and emotional
      state (via nonverbal expression), in response to emotion-evoking stimuli. A
      related objective was to assess the concordance of these two verbal and nonverbal
      measures as indices of empathy, i.e., affective responses consistent with those
      of stimulus persons. Facial expressions of 60 10-year-old girls were
      unobtrusively videotaped while they individually viewed six stimulus vignettes.
      Half of these children pressed a button to indicate awareness of emotional
      arousal while viewing stimuli; half served as controls. Results indicated that
      emotional and empathic responses were not affected by the button press procedure,
      or by a social desirability response set. Expressive responses at button presses
      were microanalytically analyzed using AFFEX. Postviewing interviews assessed
      children's reported emotions and the affect match (empathy) between children's
      reported emotion for themselves and stimulus characters. Results indicated modest
      associations between the emotions children reported and those facially displayed
      and similar associations between children's verbal and facial empathy scores.
      Results address the concurrent validity of different measures of children's
      emotions, and contribute to the small number of extant multimethod studies on
      children's emotional responses and empathy.

PMID- 7722438
TI  - Perceived reachability for self and for others by 3- to 5-year-old children and
      adults.
AB  - Ability to perceive the distance at which an object is within reach was assessed
      in 3-, 4-, and 5-year-old children and adults. In different situations, subjects
      had to judge whether an object placed in the vertical or horizontal plane was
      reachable for themselves or for someone else (the experimenter). Adults as well
      as children differentiated between the limits of their own prehensile space and
      those of another person. At all ages, children tend to attribute systematically
      more reachability to the adult experimenter. Furthermore, both children and
      adults systematically underestimate reachability for others in a horizontal
      presentation of the object. For all age groups, judgments of reachability for
      self are bodily scaled and based on perceived degrees of behavioral freedom for
      self and for others. From 3 years of age, children are shown to resemble adults
      in their ability to perceive what objects afford for action, either for self or
      for others. These results are interpreted as further evidence of early
      allocentrism (i.e., spatial decentration and perspective taking) in the context
      of a practical task.

PMID- 7722439
TI  - Selective binding of self peptides to disease-associated major histocompatibility
      complex (MHC) molecules: a mechanism for MHC-linked susceptibility to human
      autoimmune diseases.

PMID- 7722440
TI  - Expression of c-MYC under the control of GATA-1 regulatory sequences causes
      erythroleukemia in transgenic mice.
AB  - To study oncogenesis in the erythroid lineage, we have generated transgenic mice
      carrying the human c-MYC proto-oncogene under the control of mouse GATA-1
      regulatory sequences. Six transgenic lines expressed the transgene and displayed
      a clear oncogenic phenotype. Of these, five developed an early onset, rapidly
      progressive erythroleukemia that resulted in death of the founder animals 30-50 d
      after birth. Transgenic progeny of the sixth founder, while also expressing the
      transgene, remained asymptomatic for more than 8 mo, whereupon members of this
      line began to develop late onset erythroleukemia. The primary leukemic cells were
      transplantable into nude mice and syngeneic hosts. Cell lines were established
      from five of the six leukemic animals and these lines, designated
      erythroleukemia/c-MYC (EMY), displayed proerythroblast morphology and expressed
      markers characteristic of the erythroid lineage, including the erythropoietin
      receptor and beta-globin. Moreover, they also manifested a limited potential to
      differentiate in response to erythropoietin. Studies in the surviving transgenic
      line indicated that, contrary to our expectations, the transgene was not
      expressed in the mast cell lineage. That, coupled with the exclusive occurrence
      of erythroleukemia in all the transgenic lines, suggests that the GATA-1 promoter
      construct we have used includes regulatory sequences necessary for in vivo
      erythroid expression only. Additional sequences would appear to be required for
      expression in mast cells. Further, our results show that c-MYC can efficiently
      transform erythroid precursors if expressed at a vulnerable stage of their
      development.

PMID- 7722441
TI  - Early interleukin 12 production by macrophages in response to mycobacterial
      infection depends on interferon gamma and tumor necrosis factor alpha.
AB  - Interleukin 12 (IL-12) produced by macrophages immediately after infection is
      considered essential for activation of a protective immune response against
      intracellular pathogens. In the murine Mycobacterium bovis Bacillus Calmette
      Guerin (BCG) model we assessed whether early IL-12 production by macrophages
      depends on other cytokines. In vitro, murine bone marrow-derived macrophages
      produced IL-12 after infection with viable M. bovis BCG or stimulation with LPS,
      however, priming with recombinant interferon gamma (rIFN-gamma) was necessary. In
      addition, IL-12 production by these macrophages was blocked by specific anti
      tumor necrosis factor alpha (TNF-alpha) antiserum. Macrophages from gene deletion
      mutant mice lacking either the IFN-gamma receptor or the TNF receptor 1 (p55)
      failed to produce IL-12 in vitro after stimulation with rIFN-gamma and
      mycobacterial infection. In vivo, IL-12 production was induced in spleens of
      immunocompetent mice early during M. bovis BCG infection but not in those of
      mutant mice lacking the receptors for IFN-gamma or TNF. Our results show that IL
      12 production by macrophages in response to mycobacterial infection depends on
      IFN-gamma and TNF. Hence, IL-12 is not the first cytokine produced in
      mycobacterial infections.

PMID- 7722442
TI  - Stochastic coreceptor shut-off is restricted to the CD4 lineage maturation
      pathway.
AB  - Kinetics of mature T cell generation in the thymus of normal or major
      histocompatibility complex (MHC) class I- or II-deficient mice were studied by
      the bromodeoxyuridine pulse labeling method. As previously described, the early
      activation and final maturation phases were found to be synchronous for the two T
      cell lineages, but CD4+8- cells were generated faster than CD4-8+ cells in MHC
      class I- and II-deficient mice, respectively. CD8 downregulation started on day 2
      after cell proliferation even in the absence of MHC class II expression. CD8
      downregulation thus appears to be stochastic at its beginning. By contrast, CD4
      shut-off was found totally instructive, as the generation of CD4lo8+ cells with a
      high TCR density was not observed in class I-deficient mice. The analysis of the
      V beta 14 TCR frequencies in CD4/8 subsets in normal and MHC-deficient mice
      confirmed that CD4 and CD8 generation pathways are not symmetrical. These
      findings show that commitment towards the CD4+8- or CD4-8+ phenotype is
      controlled at the CD8lo step for the former and at the CD4+8+ double-positive
      stage for the latter.

PMID- 7722443
TI  - Pancreatic islet beta cells drive T cell-immune responses in the nonobese
      diabetic mouse model.
AB  - The role of autoantigens and that of target organs in which tissue lesions
      develop remains elusive in most spontaneous models of autoimmune diseases.
      Whether the presence of target autoantigens is required for the recruitment of
      autoreactive lymphocytes is unknown in most cases. To evaluate the importance of
      islet cells in the development of autoimmunity in the nonobese diabetic (NOD)
      mouse, we generated beta cell-deprived mice by injecting a high dose of alloxan,
      a toxic agent specific for beta cells. In contrast with spleen cells from 6-mo
      old naive NOD mice which transfer diabetes in irradiated 8-mo-old male
      recipients, spleen cells from age-matched NOD mice which received a single
      injection of alloxan at 3 wk of age did not transfer diabetes. With the exception
      of the ability to transfer diabetes, beta cell-deprived NOD mice showed
      maintained immune competence. Furthermore, sialitis developed with the expected
      intensity and prevalence in beta cell-deprived mice. Already committed
      "diabetogenic" spleen cells collected from spontaneously diabetic mice also
      showed a reduced capacity to transfer diabetes after their removal from the
      diabetic mice and transient "parking" in beta cell-deprived mice. Taken together,
      our data bring evidence that involvement of autoreactive T cells detected by the
      capacity to transfer diabetes requires the presence of target beta cells.

PMID- 7722444
TI  - Intermediate steps in positive selection: differentiation of CD4+8int TCRint
      thymocytes into CD4-8+TCRhi thymocytes.
AB  - The differentiation potential of putative intermediates between CD4+8+ thymocytes
      and mature T cells has been examined. Such intermediate populations were sorted,
      in parallel with CD4+8+ thymocytes, from three types of C57BL/6 mice: major
      histocompatibility complex (MHC) class II-deficient mice, mice transgenic for an
      alpha/beta T cell receptor (TCR) restricted by class I MHC and normal mice. The
      sorted populations were then transferred into the thymus of nonirradiated
      C57BL/Ka mice differing in Thy 1 allotype, and the progeny of the transferred
      cells were analyzed 2 d later. Surprisingly, with all three types of donor mice,
      a major proportion of the CD4+8intTCRint-derived progeny were found to be CD4
      8+TCRhi cells, thus delineating a new alternative pathway for development of the
      CD8 lineage. In contrast, the transfer of CD4int8+TCRint thymocytes produced CD4
      8+TCRhi cells but no significant proportion of CD4+8-TCRhi cells, suggesting that
      there is no equivalent alternative pathway for the CD4 lineage. The results
      negate some of the evidence for a stochastic/selective model of lineage
      commitment, and point to an asymmetry in the steps leading to CD4-8+ versus CD4+8
      T cells.

PMID- 7722445
TI  - Signals through T cell receptor-zeta chain alone are insufficient to prime
      resting T lymphocytes.
AB  - Activation studies performed with transfected T cell hybridomas and tumors
      revealed that chimeric molecules containing the CD3 epsilon or zeta chain
      intracytoplasmic portions can induce the complete effector functions normally
      seen only when the complete T cell receptor (TCR)/CD3 complexes of T lymphocytes
      are triggered. Therefore, the zeta chain, with its three antigen recognition
      activation motives, is thought to connect the antigen-binding Ti chains with the
      intracellular signaling machinery of the T cell. Here we demonstrate that the
      cytoplasmic portion of the TCR-zeta chain is not sufficient to activate resting T
      lymphocytes when cells from transgenic mice expressing a chimeric zeta receptor
      are used. However, after (in vivo and in vitro) activation through their
      endogenous TCR/CD3 complexes, the preactivated T lymphocytes could be triggered
      through the zeta chimera to the same extent as when they were activated through
      their endogenous TCR/CD3 complexes. They were able to proliferate and elicit
      cytotoxic functions when triggered through their zeta chimeras. These results
      suggest that the triggering requirements for effector functions seem to be
      different in resting than in activated T cells.

PMID- 7722446
TI  - Reduction in mitochondrial potential constitutes an early irreversible step of
      programmed lymphocyte death in vivo.
AB  - In a number of experimental systems in which lymphocyte depletion was induced by
      apoptosis-inducing manipulations, no apoptotic morphology and ladder-type DNA
      fragmentation were detected among freshly isolated peripheral lymphocytes ex
      vivo. Here we report that one alteration that can be detected among splenocytes
      stimulated with lymphocyte-depleting doses of dexamethasone (DEX) in vivo is a
      reduced uptake of 3,3'dihexyloxacarbocyanine iodide (DiOC6[3]), a fluorochrome
      which incorporates into cells dependent upon their mitochondrial transmembrane
      potential (delta psi m). In contrast, ex vivo isolated splenocytes still lacked
      established signs of programmed cell death (PCD):DNA degradation into high or low
      molecular weight fragments, ultrastructural changes of chromatin arrangement and
      endoplasmatic reticulum, loss in viability, or accumulation of intracellular
      peroxides. Moreover, no changes in cell membrane potential could be detected. A
      reduced delta psi m has been observed in response to different agents inducing
      lymphoid cell depletion in vivo (superantigen and glucocorticoids [GC]), in
      mature T and B lymphocytes, as well as their precursors. DEX treatment in vivo,
      followed by cytofluorometric purification of viable delta psi mlow splenic T
      cells ex vivo, revealed that this fraction of cells is irreversibly committed to
      undergoing DNA fragmentation. Immediately after purification neither delta psi
      mlow, nor delta psi mhigh cells, exhibit detectable DNA fragmentation. However,
      after short-term culture (37 degrees C, 1 h) delta psi mlow cells show
      endonucleolysis, followed by cytolysis several hours later. Incubation of delta
      psi mlow cells in the presence of excess amount of the GC receptor antagonist
      RU38486 (which displaces DEX from the GC receptor), cytokines that inhibit DEX
      induced cell death, or cycloheximide fails to prevent cytolysis. The antioxidant,
      N-acetylcysteine, as well as linomide, an agent that effectively inhibits DEX or
      superantigen-induced lymphocyte depletion in vivo, also stabilize the DiOC6(3)
      uptake. In contrast, the endonuclease inhibitor, aurintricarboxylic acid acts at
      later stages of apoptosis and only retards the transition from the viable delta
      psi mlow to the nonviable fraction. Altogether, these data suggest a sequence of
      PCD-associated events in which a reduction in delta psi m constitutes an obligate
      irreversible step of ongoing lymphocyte death, preceding other alterations of
      cellular physiology, and thus allowing for the ex vivo assessment of PCD.

PMID- 7722447
TI  - Susceptibility to tumors induced by polyoma virus is conferred by an endogenous
      mouse mammary tumor virus superantigen.
AB  - A dominant gene carried in certain inbred mouse strains confers susceptibility to
      tumors induced by polyoma virus. This gene, designated Pyvs, was defined in
      crosses between the highly susceptible C3H/BiDa strain and the highly resistant
      but H-2k-identical C57BR/cdJ strain. The resistance of C57BR/cdJ mice is overcome
      by irradiation, indicating an immunological basis. In F1 x C57BR/cdJ backcross
      mice, tumor susceptibility cosegregates with Mtv-7, a mouse mammary tumor
      provirus carried by the C3H/BiDa strain. This suggests that Pyvs might encode the
      Mtv-7 superantigen (SAG) and abrogate polyoma tumor immunosurveillance through
      elimination of T cells bearing specific V beta domains. DNA typing of 110
      backcross mice showed no evidence of recombination between Pyvs and Mtv-7.
      Strongly biased usage of V beta 6 by polyoma virus-specific CD8+ cytotoxic T
      lymphocytes in C57BR/cdJ mice implicates T cells bearing this Mtv-7 SAG-reactive
      V beta domain as critical anti-polyoma tumor effector cells in vivo. These
      results indicate identity between Pyvs and Mtv-7 sag, and demonstrate a novel
      mechanism of inherited susceptibility to virus-induced tumors based on effects of
      an endogenous superantigen on the host's T cell repertoire.

PMID- 7722448
TI  - Trypanosoma cruzi trans-sialidase: enhancement of virulence in a murine model of
      Chagas' disease.
AB  - Trypanosoma cruzi, the etiological agent of Chagas' disease, expresses a trans
      sialidase at highest levels in infective trypomastigotes, where it attaches to
      the plasma membrane by a glycophosphoinositol linkage. Bound enzyme sheds into
      the extracellular milieu in a soluble form. Experiments performed in vitro
      suggest that the trans-sialidase participates in several parameters of T. cruzi
      host interactions, like cell adhesion and complement resistance. However, the
      role that membrane-bound and soluble trans-sialidase plays in the infection of
      mammals is not understood. To begin to study the role the enzyme may play in
      vivo, T. cruzi trypomastigotes were inoculated subcutaneously into mice that had
      been sensitized for various times with the purified protein. A single dose of
      either endogenous or recombinant trans-sialidase injected into the connective
      tissues of BALB/c mice greatly enhanced parasitemia and mortality. Maximum
      enhancement was achieved with 1-2-h priming. Injection of the enzyme after the
      parasites had been established in the inoculation site had little, if any,
      consequence in modifying virulence. The enhancement did not seem to be through a
      direct effect of the enzyme on trypomastigote-host cell interactions because it
      occurred when the sites of trans-sialidase sensitization and parasite inoculation
      were physically separate. Rather, virulence enhancement seemed to depend on
      inflammatory cells, since priming with trans-sialidase had no significant effect
      in severe combined immunodeficiency mice, which lack functional T and B
      lymphocytes. However, antibody response to T. cruzi in the trans-sialidase-primed
      BALB/c mice was the same as in the control animals. Virulence enhancement was
      specific for the trans-sialidase because it did not occur in mice primed with
      Newcastle virus sialidase, which has the same substrate specificity as the T.
      cruzi enzyme, or with the sialidase from the bacterium Vibrio cholerae, whose
      substrate specificity is broader than the trypanosome sialidase. Furthermore, no
      enhancement of virulence occurred after sensitization with another adhesion
      protein (penetrin) purified from T. cruzi trypomastigotes and engineered
      bacteria, nor with bacterial lipopolysaccharide. The virulence-promoting activity
      of soluble trans-sialidase in the mouse model may be physiologically relevant
      because it was achieved with tiny doses, approximately 1-2 microgram/kg, raising
      the possibility that neutralization of the enzyme with specific probes could
      impair the development of Chagas' disease. In fact, a monoclonal antibody
      specific for the tandem repeat in the trans-sialidase COOH terminus enhanced
      infection of BALB/c mice, in agreement with earlier experiments in vitro, whereas
      antibodies against an amino acid sequence in the Cys region had the opposite
      effect.

PMID- 7722449
TI  - Intracellular targeting of antigens internalized by membrane immunoglobulin in B
      lymphocytes.
AB  - An important function of membrane immunoglobulin (mIg), the B cell antigen
      receptor, is to endocytose limiting quantities of antigen for efficient
      presentation to class II-restricted T cells. We have used a panel of mIg mutants
      to analyze the mechanism of mIg-mediated antigen presentation, and specifically
      to explore the ability of mIg to target internalized antigen to intracellular
      processing compartments. Transfected mIgs carrying substitutions for the
      transmembrane Tyr587 residue fail to efficiently present specifically bound
      antigen. However, these mutants internalize antigen normally, and their defect
      cannot be attributed to a lack of mIg-associated Ig alpha/Ig beta molecules. A
      novel functional assay for detecting antigenic peptides in subcellular fractions
      shows that wild-type mIg transfectants generate class II-peptide complexes
      intracellularly, whereas only free antigenic peptides are detectable in the
      mutant mIg transfectants. Furthermore, an antigen competition assay reveals that
      antigen internalized by the mutant mIgs fails to enter the intracellular
      processing compartment accessed by wild-type mIg. Therefore, mIg specifically
      targets bound and endocytosed antigen to the intracellular compartment where
      processed peptides associate with class II molecules, and the transmembrane
      Tyr587 residue plays an obligatory role in this process. Targeting of
      internalized antigen may be mediated by receptor-associated chaperones, and may
      be a general mechanism for optimizing the presentation of specifically bound and
      endocytosed antigens in b lymphocytes and other antigen-presenting cells.

PMID- 7722450
TI  - Detection of functional class II-associated antigen: role of a low density
      endosomal compartment in antigen processing.
AB  - We have developed a functional assay to identify processed antigen in subcellular
      fractions from antigen-presenting cells; stimulatory activity in this assay may
      be caused by either free peptide fragments or by complexes of peptide fragments
      and class II molecules present on organellar membrane sheets and vesicles. In
      addition, we have developed a functional assay to identify proteolytic activity
      in subcellular fractions capable of generating antigenic peptides from intact
      proteins. These techniques permit the direct identification of intracellular
      sites of antigen processing and class II association. Using a murine B cell line
      stably transfected with a phosphorylcholine (PC)-specific membrane-bound
      immunoglobulin (Ig), we show that PC-conjugated antigens are rapidly internalized
      and efficiently degraded to generate processed antigen within an early low
      density compartment. Proteolytic activity capable of generating antigenic peptide
      fragments from intact proteins is found within low density endosomes and a dense
      compartment consistent with lysosomes. However, neither processed peptide nor
      peptide-class II complexes are detected in lysosomes from antigen-pulsed cells.
      Furthermore, blocking the intracellular transport of internalized antigen from
      the low density endosome to lysosomes does not inhibit the generation of
      processed antigen. Therefore, antigens internalized in association with membrane
      Ig on B cells can be efficiently processed in low density endosomal compartments
      without the contribution of proteases present within denser organelles.

PMID- 7722451
TI  - Invariant chain cleavage and peptide loading in major histocompatibility complex
      class II vesicles.
AB  - B lymphocytes contain a novel population of endocytic vesicles involved in the
      transport of newly synthesized major histocompatibility complex (MHC) class II
      alpha beta chains and alpha beta peptide complexes to the cell surface. We now
      present evidence that these class II-enriched vesicles (CIIV) are also likely to
      be a site for the loading of immunogenic peptides onto MHC molecules. We used the
      serine protease inhibitor leupeptin to accumulate naturally occurring
      intermediates in the degradation of alpha beta-invariant chain complexes and to
      slow the intracellular transport of class II molecules. As expected, leupeptin
      caused an accumulation of Ii chain and class II molecules (I-A(d)) in endosomes
      and lysosomes. More importantly, however, it enhanced the selective accumulation
      of a 10-kD invariant chain fragment associated with sodium dodecyl sulfate (SDS)
      labile (empty) alpha beta dimers in CIIV. This was followed by the dissociation
      of the 10-kD fragment, formation of SDS-stable (peptide-loaded) alpha beta
      dimers, and their subsequent appearance at the cell surface. Thus, CIIV are
      likely to serve as a specialized site, distinct from endosomes and lysosomes,
      that hosts the final steps in the dissociation of invariant chain from class II
      molecules and the loading of antigen-derived peptides onto newly synthesized
      alpha beta dimers.

PMID- 7722452
TI  - Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine
      phosphorylation of signal transducer and activator of transcription (Stat)3 and
      Stat4.
AB  - Interleukin 12 (IL-12) initiates the differentiation of naive CD4+ T cells to T
      helper type 1 (Th1) cells critical for resistance to intracellular pathogens such
      as Leishmania major. To explore the basis of IL-12 action, we analyzed induction
      of nuclear factors in Th1 cells. IL-12 selectively induced nuclear DNA-binding
      complexes that contained Stat3 and Stat4, recently cloned members of the family
      of signal transducers and activators of transcription (STATs). While Stat3
      participates in signaling for several other cytokines, Stat4 was not previously
      known to participate in the signaling pathway for any natural ligand. The
      selective activation of Stat4 provides a basis for unique actions of IL-12 on Th1
      development. Thus, this study presents the first identification of the early
      events in IL-12 signaling in T cells and of ligand activation of Stat4.

PMID- 7722453
TI  - Fibrin regulates neutrophil migration in response to interleukin 8, leukotriene
      B4, tumor necrosis factor, and formyl-methionyl-leucyl-phenylalanine.
AB  - We have examined the capacity of four different chemoattractants/cytokines to
      promote directed migration of polymorphonuclear leukocytes (PMN) through three
      dimensional gels composed of extracellular matrix proteins. About 20% of PMN
      migrated through fibrin gels and plasma clots in response to a gradient of
      interleukin 8 (IL-8) or leukotriene B4 (LTB4). In contrast, < 0.3% of PMN
      migrated through fibrin gels in response to a gradient of tumor necrosis factor
      alpha (TNF) or formyl-methionyl-leucyl-phenylalanine (FMLP). All four
      chemoattractants stimulated PMN to migrate through gels composed of collagen IV
      or of basement membrane proteins (Matrigel), or through filters to which
      fibronectin or fibrinogen had been adsorbed. PMN stimulated with TNF or FMLP
      adhered and formed zones of close apposition to fibrin, as measured by the
      exclusion of a 10-kD rhodamine-polyethylene glycol probe from the contact zones
      between PMN and the underlying fibrin gel. By this measure, IL-8- or LTB4-treated
      PMN adhered loosely to fibrin, since 10 kD rhodamine-polyethylene glycol
      permeated into the contact zones between these cells and the underlying fibrin
      gel. PMN stimulated with FMLP and IL-8, or FMLP and LTB4, exhibited very little
      migration through fibrin gels, and three times as many of these cells excluded 10
      kD rhodamine-polyethylene glycol from their zones of contact with fibrin as PMN
      stimulated with IL-8 or LTB4 alone. These results show that PMN chemotaxis is
      regulated by both the nature of the chemoattractant and the composition of the
      extracellular matrix; they suggest that certain combinations of chemoattractants
      and matrix proteins may limit leukocyte movements and promote their localization
      in specific tissues in vivo.

PMID- 7722454
TI  - Differential ability of isolated H-2 Kb subsets to serve as TCR ligands for allo
      specific CTL clones: potential role for N-linked glycosylation.
AB  - It is not known whether all forms of cell surface peptide-class I complexes, when
      bound with relevant peptide antigen, are recognized by T cells. We demonstrate
      herein that two distinct subsets of the murine H-2 Kb molecule can be separately
      isolated from H-2b-expressing cell lines using Y3 mAb immunoaffinity
      chromatography. Although both isolated Kb subsets were found to be strongly
      reactive with Y3 mAb by ELISA, one Kb subset is S19.8 mAb reactive (Ly-m11+Kb
      subset) and exhibits low reactivity with the M1/42 antibody, while the other
      subset is negative for the Ly-m11 epitope and highly reactive with the M1/42
      antibody (M1/42high Kb subset). More importantly, whereas the M1/42high Kb subset
      is a very effective ligand for both TCR and CD8, the Ly-m11+ Kb subset could only
      function as a CD8 ligand, as determined in allo-specific CD8+ CTL clone adhesion
      and degranulation assays. Peptides acid-eluted from both Kb subsets sensitized Kb
      transfected T2 cells expressing "peptide empty" Kb for lysis to a similar extent
      by allo-CTL clones, indicating that relevant endogenous peptide antigens are not
      limiting in the Ly-m11+ Kb subset. The major distinction identified between the
      two Kb subsets is that they differ substantially in their degree of N-linked
      glycosylation, with the Ly-m11+ subset containing Kb molecules with larger and
      more complex carbohydrate modifications than the M1/42high subset. The
      differences in glycosylation may explain the functional differences observed
      between the two Kb subsets. It is therefore possible that some forms of
      glycosylation on class I molecules interfere with TCR recognition and may limit
      CD8+ T cell responses, perhaps under circumstances where peptide antigen is
      limiting.

PMID- 7722455
TI  - Ly-49-independent natural killer (NK) cell specificity revealed by NK cell clones
      derived from p53-deficient mice.
AB  - Natural killer (NK) cells are heterogeneous in their specificity and expression
      of cell surface molecules. In the mouse, the Ly-49A molecule is a primary
      determinant of NK cell specificity because of its ability to downregulate NK cell
      activation after physical interaction with target cell MHC class I molecules. Ly
      49A is expressed on an NK cell subset, and it belongs to a family of highly
      related molecules that may similarly dictate major histocompatibility complex
      (MHC) class I-associated specificity of Ly-49A- NK cells. It is not known,
      however, whether murine NK cell specificity may occur independently of the Ly-49
      family and target cell MHC class I molecules. Similar to the impact of cloned
      murine T cell lines on molecular description of T cell recognition, derivation of
      cloned murine NK cells should permit dissection of NK cell specificity but, to
      date, it has not been possible to produce such effector cells. In this study, we
      derived NK cell clones from mice that were homozygous for a mutation in the p53
      tumor suppressor gene. The cloned cells displayed the molecular, cell surface,
      and functional phenotype of NK cells. Significantly, the NK cell clones displayed
      clonal differences in ability to kill a panel of murine tumor targets and did not
      lyse normal cells. Target lysis was unaffected by target cell MHC class I
      expression, and none of the clones expressed Ly-49A on the cell surface or
      transcripts for Ly-49 isoforms. Although consistent with the possibility that NK
      cell specificity for MHC class I molecules is mediated by the Ly-49 family of
      molecules, the results indicate that NK cell specificity also is regulated by a
      mechanism independent of target cell MHC class I and the Ly-49 family.

PMID- 7722456
TI  - Anti-DNA antibodies bind to DNase I.
AB  - Polyspecificity is a well-known property of the anti-DNA antibodies produced by
      autoimmune animals. In our search for antigen targets of anti-DNA antibodies
      within tissue extracts, we identified a 32-kD polypeptide that was recognized by
      a large panel of anti-DNA antibodies. Direct sequencing of this protein disclosed
      its identity with DNase I. 22 monoclonal anti-DNA antibodies bound to DNase I in
      direct and competitive immunoassays; out of 15 autoantibodies that did not bind
      DNA, none had the ability to bind DNase I. The ability of anti-DNA antibodies to
      interfere with DNase I enzymatic activity was evaluated in an assay based on the
      enzyme digestion of phage double strand DNA. Six monoclonal anti-single strand
      DNA antibodies that did not bind double strand DNA were tested in this assay.
      Three out of six inhibited DNase I-mediated digestion of phage DNA. The
      interaction of anti-DNA antibodies with DNase I was further investigated by
      testing their ability to bind a synthetic peptide that corresponds to the
      catalytic site of the molecule. 4 out of 22 anti-DNA antibodies bound the active
      site peptide; two of these had been shown to inhibit DNase I enzymatic activity.
      This report show that anti-DNA antibodies recognize both DNA and its natural
      ligand DNase I. Some anti-DNA antibodies inhibit DNase I enzymatic activity, thus
      displaying the potential to modulate DNA catabolism. The dual specificity of anti
      DNA antibodies offers a clue for understanding the mechanisms that lead to anti
      DNA antibody production in autoimmune animals.

PMID- 7722457
TI  - H-2M3a violates the paradigm for major histocompatibility complex class I peptide
      binding.
AB  - The major histocompatibility (MHC) class I-b molecule H-2M3a binds and presents N
      formylated peptides to cytotoxic T lymphocytes. This requirement potentially
      places severe constraints on the number of peptides that M3a can present to the
      immune system. Consistent with this idea, the M3a-Ld MHC class I chimera is
      expressed at very low levels on the cell surface, but can be induced
      significantly by the addition of specific peptides at 27 degrees C. Using this
      assay, we show that M3a binds many very short N-formyl peptides, including N
      formyl chemotactic peptides and canonical octapeptides. This observation is in
      sharp contrast to the paradigmatic size range of peptides of 8-10 amino acids
      binding to most class I-a molecules and the class I-b molecule Qa-2.
      Stabilization by fMLF-benzyl amide could be detected at peptide concentrations as
      low as 100 nM. While N-formyl peptides as short as two amino acids in length
      stabilized expression of M3a-Ld, increasing the length of these peptides added to
      the stability of peptide-MHC complexes as determined by 27-37 degrees C
      temperature shift experiments. We propose that relaxation of the length rule may
      represent a compensatory adaptation to maximize the number of peptides that can
      be presented by H-2M3a.

PMID- 7722458
TI  - The intracellular signal transduction mechanism of interleukin 5 in eosinophils:
      the involvement of lyn tyrosine kinase and the Ras-Raf-1-MEK-microtubule
      associated protein kinase pathway.
AB  - Interleukin 5 (IL-5) regulates the growth and function of eosinophils. The
      objective of this study was to investigate the intracellular signal transduction
      mechanism of IL-5 in eosinophils. Purified eosinophils were stimulated with IL-5,
      and the involvement of various kinases was investigated by immunoblotting, immune
      complex kinase assay, and in situ denatured/renatured kinase assay. We found that
      IL-5 induced tyrosine phosphorylation and activation of a number of kinases. Two
      species of lyn kinases (53 and 56 kD) were present in eosinophils. Both forms
      were Tyr-phosphorylated and activated rapidly within 1 min. Further, lyn kinase
      was physically associated with the IL-5 beta receptor in eosinophils. Ras was
      studied by immunoprecipitation followed by thin-layer chromatography. Ras bound
      higher quantities of [alpha-32P]guanosine 5'triphosphate upon stimulation with IL
      5. Raf-1 kinase showed increased Tyr phosphorylation on immunoblotting and
      increased activity in the immune complex kinase assay. Two species of MEK (MAP or
      Erk kinase) (41 and 45 kD) were identified in eosinophils, which underwent
      autophosphorylation upon stimulation. Microtubule-associated protein (MAP) kinase
      (p44) was Tyr-phosphorylated on immunoblotting and had increased activity in the
      immune-complex kinase assay. MAP kinases were also studied after metabolic
      radiolabeling of the cells with [32P]orthophosphates. IL-5 stimulated
      phosphorylation of MAP kinases in situ. Thus, we have delineated major components
      of an important signaling pathway in eosinophils. We believe that one of the
      signals generated by IL-5 receptor activation is propagated through the lyn-Ras
      Raf-1-MEK-MAP kinase pathway.

PMID- 7722459
TI  - Peptide binding specificity of HLA-DR4 molecules: correlation with rheumatoid
      arthritis association.
AB  - We have investigated whether sequence 67 to 74 shared by beta chains of
      rheumatoid arthritis (RA)-associated HLA-DR molecules imparts a specific pattern
      of peptide binding. The peptide binding specificity of the RA-associated
      molecules, DRB1*0401, DRB1*0404, and the closely related, RA nonassociated
      DRB1*0402 was, therefore, determined using designer peptide libraries. The effect
      of single key residues was tested with site-directed mutants of DRB1*0401. The
      results have demonstrated striking differences between RA-linked and unlinked DR
      allotypes in selecting the portion of peptides that interacts with the 67-74
      area. Most differences were associated with a single amino acid exchange at
      position 71 of the DR beta chain, and affected the charge of residues potentially
      contacting position 71. The observed binding patterns permitted an accurate
      prediction of natural protein derived peptide sequences that bind selectively to
      RA-associated DR molecules. Thus, the 67-74 region, in particular position 71,
      induces changes of binding specificity that correlate with the genetic linkage of
      RA susceptibility. These findings should facilitate the identification of
      autoantigenic peptides involved in the pathogenesis of RA.

PMID- 7722460
TI  - T cell receptor repertoire in polymyositis: clonal expansion of autoaggressive
      CD8+ T cells.
AB  - In polymyositis (PM), CD8+ T cell receptor (TCR) alpha/beta + cells invade and
      destroy major histocompatibility complex class I-positive muscle fibers. We
      combined polymerase chain reaction (PCR) and double-fluorescence
      immunocytochemistry to analyze the T cell receptor (TCR) repertoire expressed in
      muscle of PM patients. In patient 1, inverse PCR revealed a preferential usage of
      TCR V alpha 33.1, V beta 13.1, and V beta 5.1. Six of six TCR V alpha 33.1+
      clones and five of seven V beta 13.1+ clones had identical nucleotide sequences.
      In contrast, the V beta 5.1+ TCRs were more heterogeneous. Similar results were
      obtained with an independent PCR method using primers specific for TCR V alpha
      33, V beta 13, or V beta 5. No TCR sequences could be amplified from
      noninflammatory control muscle. Furthermore, none of the TCR sequences found in
      PM muscle could be detected in blood from the same patient or from a normal
      control subject. Immunohistochemistry confirmed that V beta 5.1 and V beta 13.1
      were overrepresented in the muscle lesions of this patient. 32% of all CD8+ T
      cells were V beta 13.1+, and 16% were V beta 5.1+. However, approximately 60% of
      the CD8+ T cells that invaded muscle fibers were V beta 13.1+, whereas 10% were V
      beta 5.1+. In patient 2, 50% of the T cells were V beta 5.1+, and as in patient
      1, these T cells were mainly located in interstitial areas. In patient 3, > 75%
      of the autoinvasive T cells stained with an anti-V beta 3 mAb. Sequence analysis
      of 15 PCR clones amplified with a V beta 3-specific primer showed that 9 (60%)
      sequences were identical. The results suggest that (a) a strikingly limited TCR
      repertoire is expressed in PM muscle; (b) there is a dissociation between the TCR
      usage of autoinvasive and interstitial T cells; and (c) the autoinvasive T cells
      are clonally expanded.

PMID- 7722461
TI  - Autoantibodies produced spontaneously by young 1pr mice carry transforming growth
      factor beta and suppress cytotoxic T lymphocyte responses.
AB  - Young MRL/MPJ-lpr (lpr) mice 8-12 wk old challenged with alloantigen had
      significantly lower specific cytolytic T lymphocyte (CTL) responses than control
      MRL/MPJ +/+ mice. Serum from lpr mice compared with serum from ++ or normal C3H
      mice powerfully suppressed CTL responses in mixed lymphocyte cultures (MLC);
      absorbing lpr serum on protein G, adding antibody against transforming growth
      factor beta (TGF-beta) to cultures or dissociating immunoglobulin G (IgG) and TGF
      beta before additions to cultures prevented suppression. Apparently autoantibody,
      similar to IgG produced by normal mice in response to immunization, carries TGF
      beta which suppresses CTL responses in vivo and in vitro.

PMID- 7722462
TI  - Activated macrophages induce structural abnormalities of the T cell receptor-CD3
      complex.
AB  - The mechanism of the structural alterations of the T cell receptor (TCR)-CD3
      complex, which appear to be greatly responsible for immunosuppression in the
      tumor-bearing status, was investigated in tumor-bearing mice. Splenic T cells
      from tumor-bearing hosts lost the expression of the CD3 zeta chain without being
      replaced by FcR gamma, despite the normal expression of other components of the
      TCR complex. Tumor growth induced the accumulation of non-T, non-B cells in the
      spleen in correlation with the loss of zeta. Those cells were found to be
      macrophages that were able to induce the loss of zeta, as well as structural
      changes of CD3 gamma delta epsilon, even in freshly isolated normal T cells by
      cell contact-dependent interaction. More importantly, macrophages activated with
      zymosan A+LPS but not residential macrophages were able to induce the similar
      abnormality of the TCR complex. These results indicate that macrophages in
      certain activation stages play a crucial role in causing an abnormal TCR complex
      in tumor-bearing conditions, as well as in regulating the structure of the TCR
      complex in immune responses.

PMID- 7722463
TI  - Mechanism of endotoxin desensitization: involvement of interleukin 10 and
      transforming growth factor beta.
AB  - Tolerance of monocytes/macrophages to endotoxin (lipopolysaccharide [LPS]) can be
      induced both in vivo and in vitro by LPS itself. Exposure to LPS, even at a very
      low dose, induces a downregulation of cytokine response to a second high dose LPS
      challenge. To learn more about the unknown mechanisms of this phenomenon, we
      studied the role of antiinflammatory cytokines in this process. Preculture of
      human peripheral blood monocytes for 24 hours with low concentrations of LPS
      induced hyporesponsiveness to high-dose LPS rechallenge with respect to tumor
      necrosis factor (TNF) alpha and interleukin (IL) 10 but not IL-1RA production.
      These results suggest that LPS tolerance reflects a functional switch of
      monocytes rather than a general LPS hyporesponsiveness. IL-10 and transforming
      growth factor (TGF) beta 1 showed additive effects in replacing LPS for induction
      of LPS hyporesponsiveness in vitro. Additionally, neutralizing anti-IL-10 and
      anti-TGF-beta monoclonal antibodies prevented induction of LPS tolerance. In
      vitro induced LPS tolerance looks like the ex vivo LPS hyporesponsiveness of
      monocytes from septic patients with fatal outcome: downregulation of LPS-induced
      TNF-alpha and IL-10 production but not of IL-1RA secretion. LPS
      hyporesponsiveness in septic patients was preceded by expression of IL-10 at both
      the mRNA and protein level. In summary, our data suggests that IL-10 and TGF-beta
      mediate the phenomenon of LPS tolerance in vitro and perhaps in vivo (septic
      patients), too.

PMID- 7722464
TI  - The stimulatory effects of interleukin (IL)-12 on hematopoiesis are antagonized
      by IL-12-induced interferon gamma in vivo.
AB  - Interleukin (IL)-12 synergizes with other cytokines to stimulate the
      proliferation and differentiation of early hematopoietic progenitors in vitro.
      However, in vivo administration of IL-12 decreases peripheral blood counts and
      bone marrow hematopoiesis. Here, we used interferon (IFN) gamma receptor
      deficient (IFN gamma R-/-) mice to investigate whether the in vivo inhibition of
      hematopoiesis by IL-12 is indirectly mediated by IL-12-induced IFN-gamma. IL-12
      administered for 4 d (1 microgram/mouse per day) resulted in lower peripheral
      blood counts and a 2-fold decrease in bone marrow cellularity in wild-type mice,
      but not in IFN gamma R-/- mice. Bone marrow hematopoietic progenitors were
      decreased after IL-12 treatment in wild-type mice, but rather increased in IFN
      gamma R-/- mice. Splenic cellularity was 2.3-fold higher after IL-12
      administration in wild-type mice, largely due to natural killer (NK) cell and
      macrophage infiltration together with some extramedullary hematopoiesis. In IFN
      gamma R-/- mice, spleen cellularity was less increased, there were fewer
      infiltrating NK cells, but a strong extramedullary hematopoiesis. Thus,
      alterations mediated by IL-12-induced IFN-gamma include reduction in bone marrow
      cellularity and hematopoietic progenitors, as well as pronounced splenomegaly,
      largely caused by NK cell infiltration. In the absence of IFN-gamma signaling, IL
      12 promotes hematopoiesis, consistent with its in vitro activities.

PMID- 7722465
TI  - Proteolytic processing is required for viral superantigen activity.
AB  - The mouse mammary tumor virus-7 superantigen (vSAG7) is proteolytically processed
      in B cells at as many as three positions. Proteolytic processing appears to be
      important for superantigen activity because a processed form of vSAG7 was
      predominant among those forms that were found to bind to major histocompatibility
      complex class II molecules. To determine the functional significance of
      proteolytic processing, a mutation was introduced in vSAG7 at one of the sites
      where proteolytic cleavage is thought to take place in B cells. Elimination of
      the putative processing site at position 171 abrogated detectable vSAG7 surface
      expression in B cells, indicating that proteolytic processing is required for
      vSAG7 function. Coexpression in insect cells of vSAG7 and furin, a proprotein
      processing enzyme, also demonstrated that furin could process vSAG7 at position
      171.

PMID- 7722466
TI  - NKR-P1A is a target-specific receptor that activates natural killer cell
      cytotoxicity.
AB  - NKR-P1A is a lectinlike surface molecule expressed on rat natural killer (NK)
      cells. NKR-P1A has structural and functional features of an activating NK cell
      receptor, but a requirement for NKR-P1A in target cell lysis has not been
      determined. To define the role of NKR-P1A in natural killing, we have generated a
      mutant of the rat NK cell line, RNK-16, lacking expression of all members of the
      NKR-P1 receptor family. Although these NKR-P1-deficient NK cells were able to
      kill many standard tumor targets, including YAC-1, they were selectively
      deficient in the lysis of IC-21 macrophage, B-16 melanoma, and C1498 lymphoma
      targets. Reexpression of a single member of the NKR-P1 family, NKR-P1A, on mutant
      cells restored lysis of IC-21, and killing of IC-21 targets through rat NKR-P1A
      was completely blocked by F(ab')2 anti-NKR-P1A. Reexpression of NKR-P1A also
      restored transmembrane signaling to IC-21, as assessed by the generation of
      inositol-1,4,5-trisphosphate. The generation of inositol-1,4,5-trisphosphate was
      also restored in response to B-16 targets, but both B-16 and C1498 cells remained
      resistant to lysis, indicating that other NK cell molecules, perhaps within the
      NKR-P1 family, are required for the efficient killing of these tumors. These
      results are the first to demonstrate that NKR-P1A is a target-specific receptor
      that activates natural killing.

PMID- 7722467
TI  - Granzyme A is an interleukin 1 beta-converting enzyme.
AB  - Apoptosis is critically dependent on the presence of the ced-3 gene in
      Caenorhabditis elegans, which encodes a protein homologous to the mammalian
      interleukin (IL)-1 beta-converting enzyme (ICE). Overexpression of ICE or ced-3
      promotes apoptosis. Cytotoxic T lymphocyte-mediated rapid apoptosis is induced by
      the proteases granzyme A and B. ICE and granzyme B share the rare substrate site
      of aspartic acid, after which amino acid cleavage of precursor IL-1 beta (pIL-1
      beta) occurs. Here we show that granzyme A, but not granzyme B, converts pIL-1
      beta to its 17-kD mature form. Major cleavage occurs at Arg120, four amino acids
      downstream of the authentic processing site, Asp116. IL-1 beta generated by
      granzyme A is biologically active. When pIL-1 beta processing is monitored in
      lipopolysaccharide-activated macrophage target cells attacked by cytotoxic T
      lymphocytes, intracellular conversion precedes lysis. Prior granzyme inactivation
      blocks this processing. We conclude that the apoptosis-inducing granzyme A and
      ICE share at least one downstream target substrate, i.e., pIL-1 beta. This
      suggests that lymphocytes, by means of their own converting enzyme, could
      initiate a local inflammatory response independent of the presence of ICE.

PMID- 7722468
TI  - Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune
      diabetes.
AB  - Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that results
      in the destruction of the pancreatic islet beta cells. Glutamic acid
      decarboxylase (GAD) has been recently indicated as a key autoantigen in the
      induction of IDDM in nonobese diabetic mice. In human diabetes, the mechanism by
      which the beta cells are destroyed is still unknown. Here we report the first
      evidence for the presence of GAD-specific cytotoxic T cells in asymptomatic and
      recent diabetic patients. GAD65 peptides displaying the human histocompatibility
      leukocyte antigen (HLA)-A*0201 binding motif have been synthesized. One of these
      peptides, GAD114-123, binds to HLA-A*0201 molecules in an HLA assembly assay.
      Peripheral blood mononuclear cells from individuals with preclinical IDDM, recent
      onset IDDM, and from healthy controls were stimulated in vitro with the selected
      peptide in the presence of autologous antigen-presenting cells. In three cases
      (one preclinical IDDM and two recent-onset IDDM), we detected specific killing of
      autologous antigen-presenting cells when incubated with GAD114-123 peptide or
      when infected with a recombinant vaccinia virus expressing GAD65. These patients
      were the only three carrying the HLA-A*0201 allele among the subjects studied.
      Our finding suggests that GAD-specific cytotoxic T lymphocytes may play a
      critical role in the initial events of IDDM.

PMID- 7722469
TI  - Molecular behavior adapts to context: heparanase functions as an extracellular
      matrix-degrading enzyme or as a T cell adhesion molecule, depending on the local
      pH.
AB  - Migration of lymphocytes into inflammatory sites requires their adhesion to the
      vascular endothelium and subendothelial extracellular matrix (ECM). The ensuing
      penetration of the ECM is associated with the expression of ECM-degrading
      enzymes, such as endo-beta-D glucuronidase (heparanase), which cleaves heparan
      sulfate (HS) proteoglycans. We now report that, depending on the local pH, a
      mammalian heparanase can function either as an enzyme or as an adhesion molecule.
      At relatively acidified pH conditions, heparanase performs as an enzyme,
      degrading HS. In contrast, at the hydrogen ion concentration of a quiescent
      tissue, heparanase binds specifically to HS molecules without degrading them, and
      thereby anchors CD4+ human T lymphocytes. Thus, the local state of a tissue can
      regulate the activities of heparanase and can determine whether the molecule will
      function as an enzyme or as a proadhesive molecule.

PMID- 7722471
TI  - Cytoskeletal organization in clusters of isolated polarized skate hepatocytes:
      structural and functional evidence for microtubule-dependent transcytosis.
AB  - Isolated hepatocytes from the marine vertebrate Raja erinacea (the little skate)
      retain their structural and functional integrity as clusters of cells formed
      around a single tubular bile canaliculus, and therefore can be used as a model of
      polarized hepatocytes in situ. In this study we used confocal and conventional
      epifluorescence microscopy in conjunction with fluorescent markers and
      immunocytochemistry to examine the structure and function of the cytoskeleton in
      these cells. Actin filaments in the hepatocyte clusters were found cortically and
      also concentrated in a pericanalicular array, while microtubules appeared to
      radiate away from a concentration near the apical membrane of the biliary pole
      towards the basolateral sinusoidal surfaces. Treatment of clusters with the
      microtubule disrupting agent, nocodazole, resulted in the microtubules
      depolymerizing from the basolateral surfaces towards the apical surface,
      indicating that the microtubules were oriented with their plus ends at the
      basolateral surface and their minus ends at the apical surface. Nocodazole was
      also found to disrupt the ability of clusters to transcytose a fluorescent bile
      salt derivative into their canalicular lumens. We detected cytoplasmic dynein in
      skate hepatocyte homogenates by Western blotting using an anti-dynein
      intermediate chain antibody, and immunofluorescent staining of intact hepatocytes
      revealed a punctate vesicular pattern. The polarized arrangement of microtubules,
      the presence of cytoplasmic dynein, and the inhibition of bile salt secretion by
      nocodozole are consistent with the microtubule cytoskeleton playing a fundamental
      role in the mediation of transcytosis, endocytosis, and bile excretory function
      in these hepatocytes. These polarized isolated skate hepatocytes represent an
      excellent experimental model for the in vitro study of hepatic transport, and
      allow for important comparative studies aimed at elucidating the evolutionarily
      conserved nature of various hepatocyte structures amongst the vertebrates.

PMID- 7722470
TI  - Circulating allergen-reactive T cells from patients with atopic dermatitis and
      allergic contact dermatitis express the skin-selective homing receptor, the
      cutaneous lymphocyte-associated antigen.
AB  - The cutaneous lymphocyte-associated antigen (CLA) is the major T cell ligand for
      the vascular adhesion molecule E-selectin, and it has been proposed to be
      involved in the selective targeting of memory T cells reactive with skin
      associated Ag to cutaneous inflammatory sites. To further investigate the
      relation of CLA and cutaneous T cell responses, we analyzed the CLA phenotype of
      circulating memory T cells in patients with allergic contact dermatitis and
      atopic dermatitis (AD) alone vs in patients manifesting bronchopulmonary atopy
      (asthma with or without AD) and nonallergic individuals. Significant T cell
      proliferative responses to Ni, a contact allergen, and to the house dust mite
      (HDM), an allergen to which sensitization is often observed in AD and/or asthma,
      was noted only in allergic and atopic individuals, respectively. When the minor
      circulating CLA+CD3+CD45RO+ subset was separated from the major CLA-CD3+CD45RO+
      subpopulation in Ni-sensitive subjects, the Ni-dependent memory T cell response
      was largely confined to the CLA+ subset. A similar restriction of the T cell
      proliferative response to the CLA+ memory subset was observed for HDM in patients
      with AD alone. In HDM-sensitive patients with asthma with or without AD, however,
      the CLA- subset exhibited a strong antigen-dependent proliferation, in contrast
      to patients with AD alone, whose CLA- subset proliferated very weakly to HDM. In
      asthma with or without AD, the HDM-dependent proliferation slightly predominated
      in the CLA- when compared to the CLA+ subset. The functional linkage between CLA
      expression and disease-associated T cell effector function in AD was also
      demonstrated by the finding that the circulating CLA+ T cell subset in AD
      patients, but not nonatopic controls, selectively showed both evidence of prior
      activation (human histocompatibility antigen-DR expression) and spontaneous
      production of interleukin 4 but not interferon-gamma. Taken together, these
      observations demonstrate the correlation of CLA expression on circulating memory
      T cells and disease-associated memory T cell responses in cutaneous
      hypersensitivity, and they suggest the existence of mechanisms capable of sorting
      particular T cell Ag specificities and lymphokine patterns into homing receptor
      defined memory subsets.

PMID- 7722472
TI  - Epidermal cell cycle and region-specific growth during segment development in
      Artemia.
AB  - During larval development in instar IV brine shrimp, segment 1 grew by cell
      replication and cell differentiation. Cell cycle analysis revealed that the cell
      cycle was synchronized with the molt cycle. Mitosis occurred late in the instar
      and S phase began at hr 6 of the following instar. Three populations of cells
      comprised the dorsal integument. The medial-dorsal region did not grow. Cell
      enlargement occurred in the dorsal-lateral population while cell replication took
      place in the lateral population. The limb bud (ventral surface) grew in width by
      replication in the distal population, and in height by enlargement of the general
      epidermal cells in the proximal population. Expansion of each region of the
      integument was proportional to the cell growth in that region. Moreover, both
      growth processes were dependent on the level of nutrients and were enhanced by
      diets enriched in polyunsaturated fatty acids. A nutrient-dependent growth
      control point occurred in the G1 period. The commitment to replication and
      differentiation occurred by hr 2 of instar IV. The findings show that
      integumental growth is a result of region-specific cell growth processes which
      are controlled by nutrients during the G1 period.

PMID- 7722473
TI  - Histidine-rich protein B of embryonic feathers is present in the transient
      embryonic layers of scutate scales.
AB  - Based on its amino acid composition and N-terminal sequence, a polypeptide (HRP
      B) has been identified as a member of the avian histidine-rich protein (HRP)
      family. An antiserum against HRP-B has been used to localize this polypeptide in
      developing feathers and scales of chick embryos. HRP-B was first detectable in
      the barb ridge cells of feathers at 13 days of incubation and progressively
      appeared in the distal/proximal and peripheral/central gradients observed
      previously for the feather-type beta keratins in developing feathers. The HRP-B
      polypeptide was detected only in the embryonic layers of scutate scales. It first
      appeared at 16 days of incubation and was not found in the differentiated beta
      strata of these scales. At no time during the development of reticulate scales or
      apteric skin regions did the epidermal cells or cells of the embryonic layers
      express HRP-B. The transient expression of HRP-B by the embryonic layers of the
      scutate scale epidermis is discussed in light of the feather-forming potential of
      the presumptive epidermis of the scutate scale-forming region.

PMID- 7722474
TI  - Influence of pH and temperature on hemolysis by adult Schistosoma mansoni
      membranes.
AB  - Membrane fractions from homogenized adult Schistosoma mansoni are known to lyse
      host red blood cells (RBC's), which serve as an important nutrient source for the
      parasite. In order to learn more about the hemolytic process, we investigated the
      effects of pH and temperature on the steps involved in the hemolytic process. For
      maximum schistosome induced hemolysis to occur the worm lytic agent must be in
      contact with RBCs in a low pH (pH 5.1), high temperature (37 degrees C)
      environment for a short time (30 min), after which hemolysis occurs at both pH
      7.5 and 5.1. At pH 7.5 the hemolytic process is relatively temperature
      independent and highly concentration dependent. Dose-response experiments suggest
      that a multi-hit process of hemolysis is probably involved. Temperature and
      dextran experiments suggest that a pore is formed in the RBC membrane at pH 7.5.
      At pH 5.1 hemolysis is temperature dependent and not very concentration
      dependent. Dose-response data suggest that a single-hit process of hemolysis is
      utilized at low pH. The hemolytic process at pH 7.5, the pH of the host blood,
      and pH 5.1, the approximate pH of the worm gut, appears to be very different.

PMID- 7722475
TI  - Enhancing zona penetration by spermatozoa from a teratospermic species, the
      cheetah (Acinonyx jubatus).
AB  - Cheetahs (Acinonyx jubatus) produce poor quality ejaculates that can limit the
      efficiency of standard assisted reproduction including artificial insemination
      (AI) and in vitro fertilization (IVF). The purpose of this study was to: (1)
      further study sperm-oocyte interaction in this teratospermic species by examining
      the ability of malformed sperm to interact with various oocyte barriers; and (2)
      assess the potential of zona piercing for assisting IVF in a teratospermic felid.
      Zonae of salt-stored (SS), domestic cat oocytes were mechanically pierced (ZnPd)
      three times each. Semen was collected by electroejaculation from six male
      cheetahs and ejaculates were processed for IVF. Sperm aliquots from each
      ejaculate were assessed for a sperm motility index (SMI) over time. Zona-intact
      (ZnIn-SS) oocytes (n = 78) and ZnPd-SS oocytes (n = 74) were coincubated with
      spermatozoa in vitro for 6 h. The proportion of morphologically abnormal
      spermatozoa per ejaculate was high for all males (range 81.5% to 95.9%). SMI
      values at 0 and 6 h were variable, ranging from 50 to 75 and 0 to 40,
      respectively. Spermatozoa from all ejaculates bound to and penetrated the outer
      zona pellucida of ZnIn-SS and ZnPd-SS oocytes similarly (P > 0.05). The
      proportion of oocytes containing spermatozoa within the inner zona layer and the
      average number of spermatozoa per oocyte in this region were greater (P < 0.05)
      for the ZnPd-SS than ZnIn-SS oocytes (39.2% and 1.0 versus 12.8% and 0.2,
      respectively). Although zona piercing enhanced sperm penetration, there was no
      increase (P > 0.05) in pleiomorphic spermatozoa penetrating the inner zona
      pellucida or PVS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722476
TI  - Bh (black at hatch) gene appears to cause whole-body hemorrhage in homozygous
      embryos of Japanese quail (Coturnix coturnix japonica).
AB  - Genotypes of early embryos obtained from mating Bh/+ quail were determined by
      chorio-allantoic membrane grafting of their thigh skin, and the development of
      the Bh homozygous embryos was examined histologically. The Bh homozygous embryos
      died at an early stage of development (after 7 to 10 days of incubation) with a
      very high incidence of whole-body hemorrhage (approximately 100%), but
      malformation of neural tubes was not always accompanied by Bh homozygosity.
      Degeneration of the liver was more frequently observed in homozygous embryos than
      in wild-type and heterozygous embryos. The results suggest that the Bh gene
      causes whole-body hemorrhage and subsequent death of homozygous embryos. In
      addition, our data indicate that Bh homozygotes would develop brown feathers on
      their skin if they were able to survive.

PMID- 7722477
TI  - Purification of a 240 kDa protein from serum and follicular fluid of water
      buffalo and its identification as haptoglobin.
AB  - The fluids from healthy growing follicles of water buffalo were previously found
      free of the polypeptides H (M(r) 36,000) and L (M(r) 21,000) which were instead
      detected in fluids from atretic follicles and blood. Here we report evidence that
      these two polypeptides, as selected from serum by specific anti-L antibodies, are
      the subunits of an oligomeric protein. The protein was purified from serum or
      follicular fluid, and its molecular weight (240 kDa), isoelectric point (6.5),
      and amino acid composition were determined. The NH2-terminal sequences of the
      subunits L and H were analyzed: 100% and 90% homology with alpha and beta chains
      of bovine haptoglobin, respectively, was found. Thus, haptoglobin can be used as
      a novel molecular marker to assess the physiological state of the blood-follicle
      barrier or discriminate between atretic and healthy follicles.

PMID- 7722478
TI  - Anticholinesterases: medical applications of neurochemical principles.
AB  - Cholinesterases form a family of serine esterases that arise in animals from at
      least two distinct genes. Multiple forms of these enzymes can be precisely
      localized and regulated by alternative mRNA splicing and by co- or
      posttranslational modifications. The high catalytic efficiency of the
      cholinesterases is quelled by certain very selective reversible and irreversible
      inhibitors. Owing largely to the important role of acetylcholine hydrolysis in
      neurotransmission, cholinesterase and its inhibitors have been studied
      extensively in vivo. In parallel, there has emerged an equally impressive enzyme
      chemistry literature. Cholinesterase inhibitors are used widely as pesticides; in
      this regard the compounds are beneficial with concomitant health risks. Poisoning
      by such compounds can result in an acute but usually manageable medical crisis
      and may damage the CNS and the PNS, as well as cardiac and skeletal muscle
      tissue. Some inhibitors have been useful for the treatment of glaucoma and
      myasthenia gravis, and others are in clinical trials as therapy for Alzheimer's
      dementia. Concurrently, the most potent inhibitors have been developed as highly
      toxic chemical warfare agents. We review treatments and sequelae of exposure to
      selected anticholinesterases, especially organophosphorus compounds and
      carbamates, as they relate to recent progress in enzyme chemistry.

PMID- 7722479
TI  - Identification of nuclear proteins that are developmentally regulated in
      embryonic rat brain.
AB  - To identify nuclear proteins that might play a role in the acquisition of
      neuronal phenotype, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)
      was used to analyze nuclear proteins expressed over the course of embryonic rat
      brain development. Metabolically labeled rat brain nuclear proteins from
      embryonic day 14 (E14) were compared with proteins from embryonic day 20 (E20).
      Over this period, the rat brain develops from a collection of relatively
      homogeneous precursor cells into a complex structure containing many different
      classes of neurons. Computer-assisted analysis of 2D-PAGE fluorograms identified
      11 proteins that show increases in their rate of synthesis between E14 and E20.
      Twenty proteins that consistently appear at E20 are not detectable on fluorograms
      of E14 nuclear proteins, even after long exposures, and thus may be considered to
      appear de novo. Fifty-eight proteins show consistent down-regulation between E14
      and E20, and of these, 19 are not detectable on fluorograms of E20 nuclear
      proteins. The electrophoretic properties of many of these proteins suggest that
      they are previously unreported, developmentally regulated nuclear proteins. Some
      of the developmentally regulated, brain-enriched nuclear proteins identified here
      may play a role in regulating the expression of neural genes important for
      cellular differentiation in the mammalian CNS.

PMID- 7722480
TI  - Interleukin-2 transcripts in human and rodent brains: possible expression by
      astrocytes.
AB  - Cytokines have been suggested to be involved in the cross talk between the immune
      and the nervous systems, under normal and pathological conditions. For example,
      the cytokine interleukin-2 was suggested to be involved in response to CNS trauma
      and spontaneous regeneration. Here, we examined whether mammalian CNS has an
      intrinsic potential to produce interleukin-2 and, if so, what its cellular origin
      is. mRNA sequences encoding for interleukin-2 were detected in brains of humans
      and rodents. Northern blot analysis revealed the presence of several interleukin
      2 transcripts of different sizes in the brain, all recognized by lymphocyte
      derived interleukin-2 cDNA probes. One of the transcripts, a high molecular
      weight form of approximately 5 kb, appeared to be unique to the brain. Reverse
      transcription and amplification by PCR of human fetal brain mRNA revealed one
      cDNA product that, upon sequence analysis, showed a high degree of homology with
      the human lymphocyte-derived interleukin-2 coding sequence. To identify the
      possible cellular source of the interleukin-2 transcripts within the mammalian
      brain, we similarly analyzed mRNA of rat brain cells in culture. Northern blot
      analysis revealed that astrocytes contain transcripts that hybridize with
      interleukin-2 cDNA probe. These findings point to the astrocytes as a possible
      source of brain interleukin-2.

PMID- 7722481
TI  - Developmental expression and functional characterization of the 4C5 antigen in
      the postnatal cerebellar cortex.
AB  - The monoclonal antibody 4C5 recognizes a neuron-specific surface antigen (4C5
      antigen) in the CNS and PNS of the rat. In the present study we investigated the
      expression of 4C5 antigen in the developing cerebellum of the rat and the
      functional role of this molecule during cerebellar morphogenesis. Immunoblotting
      and immunohistochemistry in sections of cerebellar cortex revealed an age
      dependent decrease in the expression of the 4C5 antigen. In cerebellar primary
      cell cultures, 4C5 immunoreactivity was detected both on granule and on Purkinje
      neurons. Granule cell migration was inhibited in cerebellar explants derived from
      8-day-old rats and cultured for 2 days in the presence of antibodies against the
      4C5 antigen. Electron microscope immunocytochemistry revealed that in 8-day-old
      rat cerebellum, 4C5 immunoreactivity was localized on the cell bodies of granule
      neurons in the external and internal granular layers and on parallel fibers in
      the developing molecular layer as well as at contact sites between these cellular
      elements. It was not detected on Bergmann glia. These results suggest strongly
      that the 4C5 antigen is involved in granule cell migration during cerebellar
      development, possibly via neuron-neuron interactions.

PMID- 7722482
TI  - Synergistic stimulation of interleukin 6 release and gene expression by phorbol
      esters and interleukin 1 beta in rat cortical astrocytes: role of protein kinase
      C activation and blockade.
AB  - The involvement of protein kinase C and its interaction with interleukin 1 beta
      in the control of interleukin 6 release by cortical astrocytes was studied. The
      blockade of protein kinase C catalytic domain, by staurosporine, as well as the
      desensitization of protein kinase C by short-term phorbol 12-myristate 13-acetate
      pretreatment, increased the basal release of interleukin 6 by rat cortical
      astrocytes, whereas calphostin C, an antagonist of phorbol ester binding on
      protein kinase C regulatory domain, did not affect the basal release of the
      cytokine. The activation of protein kinase C by phorbol 12-myristate 13-acetate
      enhanced concentration- and time-dependently interleukin 6 release. This
      stimulatory action of phorbol 12-myristate 13-acetate was significantly reduced
      by staurosporine, by calphostin C and by the desensitization of protein kinase C.
      Interleukin 1 beta increased interleukin 6 release in a concentration-related
      manner. Protein kinase C inhibition, by staurosporine or desensitization,
      potentiated severalfold, whereas calphostin C reduced interleukin 1 beta
      stimulation of interleukin 6 release. The treatment of cortical astrocytes with
      both interleukin 1 beta (3 ng/ml) and phorbol 12-myristate 13-acetate (10 nM)
      caused a synergistic stimulation of interleukin 6 release and its gene
      expression, an effect that was not relieved by either 20 nM staurospine or by
      calphostin C but was slightly affected by protein kinase C desensitization. In
      conclusion, our data show that in rat cortical astrocytes the basal release of
      interleukin 6 is under a tonic inhibition exerted by a protein kinase C isoform
      or isoforms sensitive to blockade by staurosporine and desensitization but
      insensitive to calphostin C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722483
TI  - Evidence for nerve growth factor-potentiating activities of the nonpeptidic
      compound SR 57746A in PC12 cells.
AB  - SR 57746A (1-[2-(naphth-2-yl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,5,6-
      tetrahydropyridine hydrochloride) exhibits neurotrophic activities in vivo and in
      vitro. We used the rat pheochromocytoma PC12 cell line to investigate in vitro
      cellular changes induced by SR 57746A. A significant increase in the percentage
      of cells bearing neurite-like processes was obtained in cells treated by SR
      57746A and nerve growth factor (NGF) compared with NGF treatment alone. SR 57746A
      added alone, however, had no effect on morphogenesis or on survival of cells in
      serum-free medium. In contrast, SR 57746A induced a "priming" effect on PC12
      cells for neurite outgrowth within 6 h of addition of the protein tyrosine kinase
      inhibitor genistein. An increase in alpha-actinin content resulted from treatment
      with SR 57746A. Expression of NGF-mediated acetylcholinesterase and choline
      acetyltransferase was enhanced within 5 days by SR 57746A. The molecule also
      induced rapid F-actin redistribution. Within 2 min of incubation, outgrowth of F
      actin-containing filopodia was clearly visible at the cell periphery, as
      previously shown with NGF. It is interesting that this effect of SR 57746A could
      be mimicked by protein tyrosine kinase inhibitors and abolished by preincubation
      with sodium orthovanadate, a protein tyrosine phosphatase inhibitor.

PMID- 7722484
TI  - Effect of peroxynitrite on the mitochondrial respiratory chain: differential
      susceptibility of neurones and astrocytes in primary culture.
AB  - The effect of the neurotoxic nitric oxide derivative, the peroxynitrite anion
      (ONOO-), on the activity of the mitochondrial respiratory chain complexes in
      cultured neurones and astrocytes was studied. A single exposure of the neurones
      to ONOO- (initial concentrations of 0.01-2.0 mM) caused, after a subsequent 24-h
      incubation, a dose-dependent decrease in succinate-cytochrome c reductase (60% at
      0.5 mM) and in cytochrome c oxidase (52% at 0.5 mM) activities. NADH-ubiquinone-1
      reductase was unaffected. In astrocytes, the activity of the mitochondrial
      complexes was not affected up to 2 mM ONOO-. Citrate synthase was unaffected in
      both cell types under all conditions studied. However, lactate dehydrogenase
      activity released to the culture medium was increased by ONOO- in a dose
      dependent manner (40% at 0.5 mM ONOO-) from the neurones but not from the
      astrocytes. Neuronal glutathione concentration decreased by 39% at 0.1 mM ONOO-,
      but astrocytic glutathione was not affected up to 2 mM ONOO-. In isolated brain
      mitochondria, only succinate-cytochrome c reductase activity was affected (22%
      decrease at 1 mM ONOO-). We conclude that the acute exposure of ONOO- selectively
      damages neurones, whereas astrocytes remain unaffected. Intracellular glutathione
      appears to be an important factor for ameliorating ONOO(-)-mediated mitochondrial
      damage. This study supports the hypothesis that the neurotoxicity of nitric oxide
      is mediated through mitochondrial dysfunction.

PMID- 7722485
TI  - Fibroblasts that reside in mouse and frog injured peripheral nerves produce
      apolipoproteins.
AB  - Apolipoprotein synthesis and secretion is upregulated in wallerian degenerating
      peripheral nerves. A commonly expressed view has been that macrophages are solely
      responsible for their production. In the present study we provide evidence that
      (1) nerve-derived fibroblasts contribute to apolipoprotein production, (2)
      apolipoprotein production is confined to regions where myelin destruction and
      phagocytosis occur, and (3) some experimental procedures are detrimental for the
      production of apolipoproteins. Apolipoprotein production was studied in
      C57BL/6/NHSD (N) and C57/BL/6-WLD/OLA/NHSD (W) mice that display, respectively,
      rapid and slow progression of wallerian degeneration. In N nerves, apolipoprotein
      E (apo-E) is produced during in vitro and in vivo degeneration, and in vivo after
      freeze damage. In W nerves, apo-E is produced at the injury region where
      degeneration occurs but not farther distally where degeneration fails to develop.
      Apo-E is also produced in W nerves during in vitro degeneration and in vivo after
      freeze damage. In culture, N and W mice nerve-derived fibroblasts, but neither
      macrophages nor Schwann cells produced apo-E. Two apolipoproteins are produced in
      in vivo wallerian degenerating and freeze-damaged frog nerves, i.e., apo-39 and
      apo-29. Only apo-39 is produced in in vitro degenerating nerves. Neither apo-39
      nor apo-29 is produced during in vivo degeneration in diffusion chambers. In
      culture, apo-39 is produced by nerve-derived fibroblasts and macrophages but not
      by Schwann cells.

PMID- 7722486
TI  - Transfection of N-methyl-D-aspartate receptors in a nonneuronal cell line leads
      to cell death.
AB  - Neurons grown in culture die when they are exposed to high concentrations (0.1-1
      mM) of the neurotransmitter L-glutamate. A similar phenomenon may occur in the
      mammalian brain during ischemia and other injuries that cause excessive glutamate
      release. Activation of N-methyl-D-aspartate (NMDA) receptors and the consequent
      Ca2+ influx are thought to play a critical role in the process of neuronal
      toxicity. Events subsequent to the Ca2+ influx are not well understood. We have
      discovered that nonneuronal kidney cells expressing NMDA receptors after DNA
      transfection undergo cell death unless they are protected by drugs that block the
      NMDA receptor ion channel. Furthermore, transfected cells expressing a mutated
      NMDA receptor that conducts less Ca2+ are less vulnerable to cell death. In
      addition, we find that even though several active forms of NMDA receptors can be
      synthesized in these cells after transfection with different cloned subunits, not
      all receptor types are equally toxic. These experiments suggest that Ca2+ influx
      through NMDA channels may be toxic to nonneuronal cells and that the NMDA
      receptor expression may be the major neuron-specific component of excitotoxicity.

PMID- 7722487
TI  - Thiamine deficiency in cultured neuroblastoma cells: effect on mitochondrial
      function and peripheral benzodiazepine receptors.
AB  - When neuroblastoma cells were transferred to a medium of low (6 nM) thiamine
      concentration, a 16-fold decrease in total intracellular thiamine content
      occurred within 8 days. Respiration and ATP levels were only slightly affected,
      but addition of a thiamine transport inhibitor (amprolium) decreased ATP content
      and increased lactate production. Oxygen consumption became low and insensitive
      to oligomycin and uncouplers. At least 25% of mitochondria were swollen and
      electron translucent. Cell mortality increased to 75% within 5 days. [3H]PK
      11195, a specific ligand of peripheral benzodiazepine receptors (located in the
      outer mitochondrial membrane) binds to the cells with high affinity (KD = 1.4 +/-
      0.2 nM). Thiamine deficiency leads to an increase in both Bmax and KD. Changes in
      binding parameters for peripheral benzodiazepine receptors may be related to
      structural or permeability changes in mitochondrial outer membranes. In addition
      to the high-affinity (nanomolar range) binding site for peripheral benzodiazepine
      ligands, there is a low-affinity (micromolar range) saturable binding for PK
      11195. At micromolar concentrations, peripheral benzodiazepines inhibit thiamine
      uptake by the cells. Altogether, our results suggest that impairment of oxidative
      metabolism, followed by mitochondrial swelling and disorganization of cristae, is
      the main cause of cell mortality in severely thiamine-deficient neuroblastoma
      cells.

PMID- 7722488
TI  - Prolonged time course of glutamate release from nerve terminals: relationship
      between stimulus duration and the secretory event.
AB  - The kinetics of synaptosomal [3H]glutamate release were measured on a subsecond
      time scale to study the relationship between the length of depolarization and the
      duration of the secretory event. The time course of release evoked by elevated K+
      was complex, proceeding for several seconds after a 200-ms depolarization. We
      developed a protocol for depolarizing excitable membranes on a millisecond time
      scale to deliver brief depolarizations, termed the synthetic action potential, by
      using batrachotoxin to activate Na+ channels. Depolarization is achieved by
      superfusing with solutions containing elevated concentrations of Na+, and the
      duration of the depolarization is limited by including tetrodotoxin (TTX) in the
      superfusion solution to block Na+ current and membrane depolarizations were made
      in batrachotoxin-treated sensory neurons using patch clamp recording methods.
      Rapid increases in Na+ and TTX concentrations produced transient increases in
      inward Na+ current that decayed with a time course proportional to TTX
      concentration. Current clamp measurements indicated that, with 10 microM TTX,
      depolarizations last approximately 30 ms. Nonetheless, synaptosomal release of
      [3H]glutamate triggered by the synthetic action potential remained prolonged.
      Brief neuronal action potentials at some synapses may trigger transmitter release
      that persists for several seconds.

PMID- 7722489
TI  - NMDA receptor subtype selectivity: eliprodil, polyamine spider toxins,
      dextromethorphan, and desipramine selectively block NMDA-evoked striatal
      acetylcholine but not spermidine release.
AB  - NMDA receptor stimulation concomitantly increases the release of
      [14C]acetylcholine and [3H]-spermidine from rat striatal slices in vitro. The
      NMDA-induced release of both acetylcholine and spermidine was blocked with equal
      potency by the NMDA channel blocker phencyclidine (0.1-10 microM). However,
      certain other channel blockers, including dextromethorphan (1-100 microM), which
      antagonized NMDA-evoked acetylcholine release without affecting NMDA-evoked
      spermidine release, and dextrorphan (1-100 microM) and memantine (1-100 microM),
      which block NMDA-evoked acetylcholine release more potently than NMDA-evoked
      spermidine release, showed greater selectivity of action. As previously shown for
      ifenprodil, eliprodil (SL82.0715; 1-100 microM) blocked NMDA-evoked acetylcholine
      but not spermidine release. This selectivity is also observed for other agents
      interacting with the polyamine site(s) on the NMDA receptor, including arcaine (1
      1,000 microM), philanthotoxin343, and argiotoxin636 (10 microM) and was also
      noted for desipramine (1-100 microM). The NMDA-induced release of acetylcholine
      and spermidine is likely to be mediated by different native NMDA receptor
      subtypes, and several NMDA antagonists may be candidates for a selective action
      at a particular NMDA receptor subtype.

PMID- 7722490
TI  - Blockade of neurotensin receptor by SR 48692 potentiates the facilitatory effect
      of haloperidol on the evoked in vivo dopamine release in the rat nucleus
      accumbens.
AB  - The present experiments assessed the effects of SR 48692, a selective nonpeptide
      antagonist of neurotensin receptors, on mesolimbic dopaminergic
      neurotransmission. Dopamine release evoked by the electrical stimulation of the
      median forebrain bundle (20 Hz, 10 s) was measured in the nucleus accumbens of
      urethane-anesthetized rats using differential pulse amperometry combined with
      carbon fiber electrodes. SR 48692 (0.1 mg/kg, i.p.) alone did not affect this
      release, whereas it dose-dependently (0.03-1 mg/kg, i.p.) enhanced the
      haloperidol (50 micrograms/kg, i.p.)-induced facilitation of the electrically
      evoked DA release. The increase induced by haloperidol (92 +/- 26% above control
      values 30 min after injection) was potentiated by SR 48692 (264 +/- 75% at 0.03
      mg/kg, 428 +/- 113% at 0.1 mg/kg, and 480 +/- 135% at 1 mg/kg). Effects identical
      to those of SR 48692 were obtained with SR 48527, a chemically related compound
      with a high affinity for neurotensin receptors, but not with SR 49711, its low
      affinity antipode. The potentiating effects of SR 48692 were positively related
      to the stimulation frequency (from 6 to 20 Hz) and to the dose of haloperidol
      (from 12.5 to 50 micrograms/kg) and were abolished after prior kainic acid lesion
      (1 microgram/1 microliter) of the nucleus accumbens. Thus, the effects of SR
      48692 required the integrity of postsynaptic elements of the nucleus accumbens
      and occurred under the combination of two, at least partly, interdependent
      conditions: strong D2 autoreceptor blockade and high-intensity stimulation likely
      to release neurotensin. It is interesting that these potentiating effects of SR
      48692 did not appear in the striatum. In conclusion, these findings suggest that
      endogenous neurotensin may attenuate the facilitation of D2 receptor blockade on
      mesolimbic but not nigrostriatal dopamine transmission.

PMID- 7722491
TI  - NMDA receptor blockade increases in vivo striatal dopamine synthesis and release
      in rats and mice with incomplete, dopamine-depleting, nigrostriatal lesions.
AB  - The role of excitatory amino acids (EAAs) in the regulation of striatal dopamine
      (DA) synthesis and release in rats and mice with incomplete DA-depleting lesions
      of the nigrostriatal system was investigated using in vivo microdialysis in rats
      and estimates of striatal in vivo tyrosine hydroxylase activity in mice.
      Dopaminergic nigrostriatal input to the striatum was partially lesioned in rats
      with stereotactic perinigral 6-hydroxydopamine injections and in C57BL mice with
      systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. In rats,
      addition of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP-5,
      10 mM) to dialysate increased local striatal DA release and synthesis. In 6
      hydroxydopamine partially lesioned rats, the effects of AP-5 on DA release were
      significantly diminished, and AP-5 had no significant effect on DA synthesis.
      Perfusion with the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione
      (DNQX, 1 mM) alone increased DA synthesis slightly, whereas DNQX + AP-5 (10 mM)
      increased DA synthesis to levels comparable with those observed with AP-5 alone.
      Local striatal DA synthesis was also increased by addition of the NMDA receptor
      antagonist (+/-)-3-(2-carboxypiperizin-4-yl)propyl-1-phosphonic acid (CPP, 1 mM)
      to the perfusion buffer. Local inhibition of nitric oxide synthase with nitro-L
      arginine (10 mM) perfused through the striatal microdialysis probe did not alter
      DA synthesis, suggesting that the effects observed with NMDA receptor blockade
      are not mediated by nitric oxide. In unlesioned mice, none of the systemically
      injected EAA receptor antagonists altered striatal DA synthesis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7722492
TI  - Role of cyclic GMP in the regulation of neuronal calcium and survival by secreted
      forms of beta-amyloid precursor.
AB  - The Alzheimer's disease (AD) beta-amyloid precursor proteins (beta APPs) are
      large membrane-spanning proteins that give rise to the beta A4 peptide deposited
      in AD amyloid plaques. beta APPs can also yield soluble forms (APPss) that are
      potently neuroprotective against glucose deprivation and glutamate toxicity,
      perhaps through their ability to lower the intraneuronal calcium concentration
      ([Ca2+]i). We have investigated the mechanism through which APPss exert these
      effects on cultured hippocampal neurons. The ability of APPss to lower rapidly
      [Ca2+]i was mimicked by membrane-permeable analogues of cyclic AMP (cAMP) and
      cyclic GMP (cGMP), as well as agents that elevate endogenous levels of these
      cyclic nucleotides. However, only cGMP content was increased by APPs treatment,
      and specific inhibition of cGMP-dependent protein kinase (but not cAMP-dependent
      kinase) blocked the activity of APPss. A membrane-permeable analogue of cGMP (8
      bromo-cGMP) also mimicked the ability of APPss to attenuate the elevation of
      [Ca2+]i by glutamate, apparently through inhibition of NMDA receptor activity. In
      addition, 8-bromo-cGMP afforded protection against glucose deprivation and
      glutamate toxicity, and the protection by APPss against glucose deprivation was
      blocked by an inhibitor of cGMP-dependent kinase. Together, these data suggest
      that APPss mediate their [Ca2+]i-lowering and excitoprotective effects on target
      neurons through increases in cGMP levels.

PMID- 7722493
TI  - Involvement of bidirectional adenosine transporters in the release of L
      [3H]adenosine from rat brain synaptosomal preparations.
AB  - Adenosine transport inhibitors as enhancers of extracellular levels of endogenous
      adenosine would, presumably, only be effective if, for example, (1) the
      inhibitors block influx to a greater degree than efflux (release) of
      intracellular adenosine or (2) the inhibitors block equally well the influx and
      efflux of adenosine, but significant amounts of adenosine are formed as a result
      of dephosphorylation of released adenine nucleotides. Limited information is
      available regarding the directional symmetry of adenosine transporters in neural
      cells. Using rat brain crude P2 synaptosomal preparations preloaded with L
      [3H]adenosine, our objectives here were to determine (1) if L-[3H]adenosine, a
      substrate for adenosine transporters that is more metabolically stable than
      physiological D-adenosine, was being released from synaptosomal preparations, (2)
      the optimal conditions necessary to observe the release, and (3) the degree to
      which this release was mediated by efflux through bidirectional nucleoside
      transporters. L-[3H]Adenosine release was found to be concentration and time
      dependent, temperature sensitive, and linear with synaptosomal protein. L
      [3H]Adenosine release was inhibited dose-dependently by dipyridamole,
      nitrobenzylthioinosine, and dilazep; at concentrations of 100 microM inhibition
      was at least 40% for dipyridamole, 52% for nitrobenzylthioinosine, and 49% for
      dilazep. After loading with L-[3H]adenosine alone or I-[3H]adenosine plus
      unlabeled L-adenosine, D-adenosine, or uridine, L-[3H]adenosine release was
      inhibited 42% by L-adenosine, 69% by uridine, and 81% by D-adenosine.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7722494
TI  - Pituitary adenylate cyclase-activating polypeptide: control of rat pineal cyclic
      AMP and melatonin but not cyclic GMP.
AB  - In this study, the effects of pituitary adenylate cyclase-activating polypeptide
      (PACAP) on cyclic nucleotide accumulation and melatonin (MT) production in
      dispersed rat pinealocytes were measured. Treatment with PACAP (10(-7) M)
      increased MT production 2.5-fold. PACAP (10(-7) M) also increased cyclic AMP
      accumulation four- to fivefold; this effect was potentiated two- to three-fold by
      alpha 1-adrenergic activation. This potentiation appears to involve protein
      kinase C (PKC) because alpha 1-adrenergic activation is known to translocate PKC
      and the PACAP-stimulated cyclic AMP accumulation was potentiated ninefold by a
      PKC activator, 4 beta-phorbol 12-myristate 13-acetate (PMA). Phenylephrine and
      PMA also potentiated the PACAP-stimulated MT accumulation. These results indicate
      that cyclic AMP is one second messenger of PACAP in the pineal gland and that the
      effects of PACAP on cyclic AMP and MT production can be potentiated by an alpha 1
      adrenergic-->PKC mechanism. In addition to these findings, it was observed that
      PACAP treatment with or without phenylephrine or PMA did not alter cyclic GMP
      accumulation. This indicates that PACAP is the first ligand identified that
      increases cyclic AMP accumulation in the pineal gland without increasing cyclic
      GMP accumulation. That PACAP fails to activate the vasoactive intestinal
      peptide/cyclic GMP pathway suggests that the vasoactive intestinal peptide
      receptors present in the pineal may be distinct from the type II PACAP receptors.

PMID- 7722495
TI  - Differential coupling of D1 and D5 dopamine receptors to guanine nucleotide
      binding proteins in transfected GH4C1 rat somatomammotrophic cells.
AB  - D1 and D5 dopamine receptor genes, stably expressed in GH4C1 rat
      somatomammotrophic cells, display identical binding values and stimulate
      adenylate cyclase. Approximately 60% of D1 receptors were in the agonist high
      affinity state and were converted to the low-affinity state by 100 microM guanyl
      5'-ylimidodiphosphate [Gpp(NH)p]. Of the 48% of D5 receptors in the high-affinity
      state, only half were modulated by 100 microM Gpp(NH)p; in the presence of the G
      protein activator, AIF4-, the high-affinity sites of D5 receptors were abolished
      by Gpp(NH)p, suggesting tight coupling between D5 receptors and G proteins. The
      high-affinity sites of D1, but not D5, receptors were reduced after pertussis
      toxin treatment of cells. Thus, whereas D1 receptors in GH4C1 cells couple to
      both Gs, the G stimulatory protein, and a pertussis toxin-sensitive G protein, D5
      receptors couple to Gs and a pertussis toxin-insensitive G protein. Neither D1
      nor D5 receptors were able to stimulate phosphoinositide metabolism in these
      cells. The ability of D5, but not D1, receptors to couple to novel G proteins may
      be significant in assigning a functional role for these receptors.

PMID- 7722496
TI  - Transport of gabapentin, a gamma-amino acid drug, by system l alpha-amino acid
      transporters: a comparative study in astrocytes, synaptosomes, and CHO cells.
AB  - The system L transporter is generally considered to be one of the major Na(+)
      independent carriers for large neutral alpha-amino acids in mammalian cells.
      However, we found that cultured astrocytes from rat brain cortex accumulate
      gabapentin, a gamma-amino acid, predominately by this alpha-amino acid transport
      system. Uptake of gabapentin by system L transporter was also examined in
      synaptosomes and Chinese hamster ovary (CHO) cells. The inhibition pattern
      displayed by various amino acids on gabapentin uptake in astrocytes and
      synaptosomes corresponds closely to that observed for the system L transport
      activity in CHO cells. Gabapentin and leucine have Km values that equal their Ki
      values for inhibition of each other, suggesting that leucine and gabapentin
      compete for the same system L transporter. By contrast, gabapentin exhibited no
      effect on uptake of GABA, glutamate, and arginine, indicating that these latter
      three types of brain transporters do not serve for uptake of gabapentin. A
      comparison of computer modeling analysis of gabapentin and L-leucine structures
      shows that although the former is a gamma-amino acid, it can assume a
      conformation that can resemble the L-form of a large neutral alpha-amino acid
      such as L-leucine. The steady-state kinetic study in astrocytes and CHO cells
      indicates that the intracellular concentrations of gabapentin are about two to
      four times higher than that of leucine. The uptake levels of these two substrates
      are inversely related to their relative exodus rates. The concentrating ability
      by system L observed in astrocytes is consistent with the substantially high
      accumulation gradient of gabapentin in the brain tissue as determined by
      microdialysis.

PMID- 7722497
TI  - Glutamate-induced loss of Ca2+/calmodulin-dependent protein kinase II activity in
      cultured rat hippocampal neurons.
AB  - The exposure of cultured rat hippocampal neurons to 500 microM glutamate for 20
      min induced a 55% decrease in the total Ca2+/calmodulin-dependent protein kinase
      II (CaM kinase II) activity. The Ca(2+)-independent activity and
      autophosphorylation of CaM kinase II decreased to the same extent as the changes
      observed in total CaM kinase II activity, and these decreases in activities were
      prevented by pretreatment with MK-801, an N-methyl-D-aspartate (NMDA)-type
      receptor antagonist, and the removal of extracellular calcium but not by
      antagonists against other types of glutamate receptors and protease inhibitors.
      Similarly, the decrease in the CaM kinase II activity was induced by a Ca2+
      ionophore, ionomycin. Immunoblot analysis with the anti-CaM kinase II antibody
      revealed a significant decrease in the amount of the enzyme in the soluble
      fraction, in contrast with the inverse increase in the insoluble fraction; thus,
      the translocation was probably induced during treatment of the cells with
      glutamate. These results suggest that glutamate released during brain ischemia
      induces a loss of CaM kinase II activity in hippocampal neurons, by stimulation
      of the NMDA receptor, and that inactivation of the enzyme may possibly be
      involved in the cascade of the glutamate neurotoxicity following brain ischemia.

PMID- 7722498
TI  - Full-length and truncated Alzheimer amyloid precursors in chromaffin granules:
      solubilization of membrane amyloid precursor is mediated by an enzymatic
      mechanism.
AB  - The amyloid beta peptide (A beta) of Alzheimer disease is derived from the
      proteolytic processing of the amyloid precursor proteins (APPs), which are
      considered type I transmembrane proteins. Here we report that the soluble
      fraction of isolated adrenal medullary chromaffin granules (CG), a model neuronal
      secretory vesicle system, contains an antigen that immunochemically and on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis was indistinguishable from
      full-length APP. A truncated APP fragment with intact A beta sequence was also
      detected in the soluble fraction of CG. In vitro experiments showed that full
      length APP was solubilized from CG membranes at 37 degrees C as a function of pH,
      with a peak of activity between pH 8.5 and pH 9.0. Solubilization of full-length
      APP was inhibited by several protease inhibitors, including aprotinin, cystatin,
      and iodoacetamide, by the divalent cations Ca2+ and Zn2+, and by preheating of
      the membranes. These results are consistent with and suggest the involvement of
      an enzymatic mechanism in the solubilization of potentially amyloidogenic full
      length APP. Production of A beta from a transmembrane APP predicts a proteolytic
      cleavage within the lipid bilayer, a site relatively inaccessible to proteases.
      Thus, the detected soluble, potentially amyloidogenic, full-length APP may be a
      substrate for the proteases producing A beta. The detection of soluble APP with
      intact A beta sequence in secretory vesicles is consistent with the extracellular
      topology of amyloid depositions.

PMID- 7722499
TI  - Ca2+/calmodulin kinase II translocates in a hippocampal slice model of ischemia.
AB  - Rat hippocampal slices were exposed to conditions that simulate an ischemic
      insult, and the subcellular distribution and the enzymatic activity of
      Ca2+/calmodulin-dependent protein kinase II (CaM kinase) were monitored.
      Semiquantitative western blots using a monoclonal antibody to the 50-kDa alpha
      subunit showed that there was a significant redistribution of the enzyme from a
      supernatant to a pellet fraction after 10 min of an anoxic/aglycemic insult. No
      significant change in the total amount of CaM kinase enzyme was detected in the
      homogenates for up to 20 min of exposure to the insult. Ca2+/CaM-dependent enzyme
      activity did not significantly change in the pellet during the 20-min insult.
      Supernatant activity decreased throughout the insult. The persistence of Ca2+/CaM
      dependent CaM kinase activity in the pellet fraction and the detected movement of
      enzyme from the supernatant to the pellet indicate that redistribution may be an
      important mechanism in regulating the cellular location of CaM kinase activity.

PMID- 7722500
TI  - Regionally selective and age-dependent alterations in benzodiazepine receptor
      binding in the genetically dystonic hamster.
AB  - Previous pharmacological studies have indicated that impairment of GABAergic
      transmission may be involved in the pathophysiology of dystonia in the mutant
      dtsz hamster, i.e., a genetic animal model for idiopathic dystonia. In the
      present experiments, the kinetic constants of [3H]flumazenil binding to the
      benzodiazepine site of the GABAA receptor were calculated from equilibrium
      binding measurements in various brain regions of genetically dystonic hamsters
      and age-matched controls. Because dystonia in mutant dtsz hamsters is transient
      and disappears after approximately 60-70 days of age, [3H]flumazenil binding was
      studied at the age of maximum severity of dystonia (30-40 days) and after
      disappearance of the disease, to examine which neurochemical changes were related
      to dystonia. In mutant hamsters with the maximum severity of dystonia, receptor
      affinity of [3H]flumazenil was increased in olfactory bulb, striatum, tectum, and
      cerebellum, as exemplified by significantly decreased dissociation constants (KD)
      in these regions. An increased number of binding sites (Bmax) were seen in
      striatum and frontal cortex but not in the other eight regions studied in this
      regard. All these changes in [3H]flumazenil binding disappeared in parallel with
      dystonia, implicating a causal relationship between altered benzodiazepine
      receptor binding and dystonia in mutant dtsz hamsters.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7722501
TI  - Lipid metabolism and membrane composition are altered in the brains of type II
      diabetic mice.
AB  - CBL/57 strain db/db mice exhibit type II (noninsulin-dependent) diabetes. The
      affected mice are markedly hyperinsulinemic, hyperglycemic, and
      hypercholesterolemic, and their serum K+ levels are decreased. The brains of the
      diabetic mice are significantly smaller than those of their lean, control
      littermates, but the protein concentration is normal. The low brain weight is
      accompanied by a loss of major fatty acid components within the whole brain,
      nerve endings, and mitochondrial membranes. Cholesterol levels are low in whole
      brain but are not significantly different from normal in the synaptosomal
      membranes. The phospholipid concentration is significantly decreased in whole
      brain homogenates, crude synaptosomal membranes, and crude mitochondrial
      membranes of the diabetic mice. In addition, the specific activities of membrane
      bound synaptosomal acetylcholinesterase, Na+,K(+)-ATPase, and Mg(2+)-ATPase are
      decreased in crude synaptosomal membranes of the diabetic mice. The specific
      activities of carnitine palmitoyltransferase I and carnitine acetyltransferase
      are significantly increased in the crude mitochondrial fraction isolated from the
      brains of the type II diabetic mice, whereas the specific activity of pyruvate
      dehydrogenase complex is decreased. The specific activities of two other
      mitochondrial enzymes--monoamine oxidase B and citrate synthase--and a cytosolic
      enzyme--lactate dehydrogenase--are unaltered. The ability to synthesize cyclic
      AMP is markedly decreased in the brains of the diabetic mice. The concentrations
      of carnitine and of the amino acids, glutamate, aspartate, glutamine, and serine
      are unaltered, whereas glycine levels are significantly elevated in the brains of
      the db/db mice. The data suggest that in vivo the brains of the diabetic mice
      exhibit a decreased capacity for glucose oxidation and increased capacity for
      fatty acid oxidation. This hypothesis is supported by the finding that cerebral
      mitochondria isolated from the db/db mice oxidize [1-14C]palmitate to 14CO2 at a
      rate almost twice that of control mitochondria. The present findings emphasize
      the potentially serious alteration of brain metabolism in uncontrolled type II
      diabetes.

PMID- 7722502
TI  - Tellurite specifically affects squalene epoxidase: investigations examining the
      mechanism of tellurium-induced neuropathy.
AB  - A peripheral neuropathy characterized by a transient demyelinating/remyelinating
      sequence results when young rats are fed a tellurium-containing diet. The
      neuropathy occurs secondary to a systemic block in cholesterol synthesis.
      Squalene accumulation suggested the lesion was at the level of squalene
      expoxidase, a microsomal monooxygenase that uses NADPH cytochrome P450 reductase
      to receive its necessary reducing equivalents from NADPH. We have now
      demonstrated directly specificity for squalene epoxidase; our in vitro studies
      show that squalene epoxidase is inhibited 50% in the presence of 5 microM
      tellurite, the presumptive in vivo active metabolite. Under these conditions, the
      activities of other monooxygenases, aniline hydroxylase and benzo(a)pyrene
      hydroxylase, were inhibited less than 5%. We also present data suggesting that
      tellurite inhibits squalene epoxidation by interacting with highly susceptible 
      SH groups present on this monooxygenase. In vivo studies of specificity were
      based on the compensatory response to feeding of tellurium. Following tellurium
      intoxication, there was up-regulation of squalene epoxidase activity both in
      liver (11-fold) and sciatic nerve (fivefold). This induction was a specific
      response, as demonstrated in liver by the lack of up-regulation following
      exposure to the nonspecific microsomal enzyme inducer, phenobarbital. As a
      control, we also measured the microsomal monooxygenase activities of aniline
      hydroxylase and benzo(a)pyrene hydroxylase. Although they were induced following
      phenobarbital exposure, activities of these monooxygenases were not affected
      following tellurium intoxication, providing further evidence of specificity of
      tellurium intoxication for squalene epoxidase.

PMID- 7722503
TI  - Oxypurinol-enhanced postischemic recovery of the rat brain involves preservation
      of adenine nucleotides.
AB  - The present study investigated the effect of the administration of oxypurinol (40
      mg/kg), an inhibitor of xanthine oxidase, on adenosine and adenine nucleotide
      levels in the rat brain during ischemia and reperfusion. The brains of the
      animals were microwaved before, at the end of a 20-min period of cerebral
      ischemia, and after 5, 10, 45, and 90 min of reperfusion. Cerebral ischemia was
      elicited by four-vessel occlusion with arterial hypotension to 45-50 mm Hg.
      Adenosine and adenine nucleotide levels in the oxypurinol-pretreated
      (administered intravenously 20 min before ischemia) rats were compared with those
      in nontreated animals exposed to the same periods of ischemia and reperfusion.
      Oxypurinol administration resulted in significantly elevated ATP levels at the
      end of ischemia and 5 min after ischemia, but not at 10 min after ischemia. ADP
      levels were also elevated, in comparison with those in the control rats, at the
      end of the ischemic period. Conversely, AMP levels were significantly reduced at
      the end of ischemia and during the initial (5 min) period of reperfusion.
      Adenosine levels were lower in oxypurinol-treated rats, during ischemia, and in
      the initial reperfusion phase. Oxypurinol administration resulted in a
      significant increase in the energy charge both during ischemia and after 5 min of
      reperfusion. Physiological indices, namely, time to recovery of mean arterial
      blood pressure and time to onset of respiration, were also shortened in the
      oxypurinol-treated animals. These beneficial effects of oxypurinol may have been
      a result of its purine-sparing (salvage) effects and of its ability to inhibit
      free radical formation by the enzyme xanthine oxidase. Preservation of high
      energy phosphates during ischemia likely contributes to the cerebroprotective
      potency of oxypurinol.

PMID- 7722504
TI  - Delayed neuronal death after brief histotoxic hypoxia in vitro.
AB  - The effect of three metabolic inhibitors--iodoacetate, potassium cyanide, and
      potassium arsenate--on neuronal viability was studied in primary rat cortical and
      hippocampal CA1 neuronal cultures. Iodoacetate (0.1 mM) applied for 5 min to 8
      day-old cultures resulted in delayed neuronal death within 3-24 h in cortical and
      hippocampal CA1 neurons. Neuronal degeneration was preceded by transient
      inhibition of energy metabolism to approximately 40% and a permanent inhibition
      of protein synthesis to approximately 50%. The inhibition of protein synthesis
      and the neuronal death were prevented by the free radical scavenger vitamin E but
      not by the glutamate antagonist MK-801. Removal of calcium during iodoacetate
      exposure could not protect against toxicity, and there was no increase of
      intracellular calcium concentration during and shortly after iodoacetate
      treatment. Cyanide and arsenate produced only partial neuronal degeneration, even
      at a dose of 10 mM. These observations demonstrate that brief exposure of neurons
      to low concentrations of iodoacetate produces a delayed type of neuronal death
      that is not mediated by either calcium or glutamate. The therapeutic effect of
      vitamin E points to a free-radical mediated injury and suggests that this type of
      pathology may also be involved in delayed neuronal death after transient energy
      depletion in vivo.

PMID- 7722505
TI  - Variant forms of neuronal glutamate transporter sites in Alzheimer's disease
      cerebral cortex.
AB  - The displacement of Na(+)-dependent D-[3H]-aspartate binding by unlabeled D
      aspartate or the inhibitors DL-threo-beta-hydroxyaspartate, L-cysteate, L
      glutamate, dihydrokainate, DL-alpha-aminoadipate, alpha-methyl-DL-glutamate, and
      1-aminocyclobutane-cis-1,3-dicarboxylate was used to characterize the high
      affinity glutamate/aspartate uptake site in human cerebral cortex. Synaptosomal
      membranes were prepared from tissue obtained at autopsy from nondemented control,
      Alzheimer's disease (AD), and diffuse Lewy body disease (DLBD) cases. Areas that
      are damaged in AD (midtemporal, frontal, caudal cingulate, and hippocampal
      cortices) were compared with those that are spared (occipital and motor
      cortices). Profiles of the affinities (Ka values) of the ligands showed that
      areas spared from damage in AD cases differed significantly from equivalent areas
      in control (p < 0.001) and DLBD (p < 0.001) cases and also from areas susceptible
      to damage in the same AD cases (p < 0.001). Areas susceptible to damage in AD
      showed comparable profiles across the three case groups (p = 0.980). The
      glutamate/aspartate uptake site may be regionally variant in AD cases, and this
      may underlie local excitotoxicity. D-[3H]Aspartate binding site density was
      significantly lower in both dementia groups (control vs. AD, p < 0.001; control
      vs. DLBD, p = 0.009; but AD vs. DLBD, p = 0.528); within-group differences were
      not significant (control, p = 0.874; AD, p = 0.285; DLBD, p = 0.741).

PMID- 7722506
TI  - Characterization of a novel phospholipase A2 activity in human brain.
AB  - Phospholipases A2 (PLA2) are a family of enzymes that catalyze the removal of
      fatty acid residues from phosphoglycerides. The enzyme is postulated to be
      involved in several human brain disorders, although little is known regarding the
      status of PLA2 activity in human CNS. We therefore have characterized some
      aspects of the PLA2 activity present in the temporal cortex of human brain. More
      PLA2 activity was found in the membrane (particulate) fraction than in the
      cytosolic fraction. The enzyme could be solubilized from particulate material
      using 1 M potassium chloride, and was capable of hydrolyzing choline
      phosphoglyceride (CPG) and ethanolamine phosphoglyceride (EPG), with a preference
      (approximately eightfold) for EPG over CPG. When the solubilized particulate
      enzyme was subjected to gel filtration chromatography, PLA2 activity eluted in a
      high molecular mass fraction (approximately 180 kDa). PLA2 activity was weakly
      stimulated by dithiothreitol, strongly stimulated by millimolar concentrations of
      calcium ions, and inhibited by brief heat treatment at 57 degrees C,
      bromophenacyl bromide, the arachidonic acid derivative AACOCF3, gamma-linolenoyl
      amide, and N-methyl gamma-linolenoyl amide. Thus, whereas the human brain
      enzyme(s) characterized in our study displays some of the characteristics of
      previously characterized PLA2s, it differs in several key features.

PMID- 7722507
TI  - Changes of respiratory chain activity in mitochondrial and synaptosomal fractions
      isolated from the gerbil brain after graded ischaemia.
AB  - In this study we have examined (1) the integrated function of the mitochondrial
      respiratory chain by polarographic measurements and (2) the activities of the
      respiratory chain complexes I, II-III, and IV as well as the ATP synthase
      (complex V) in free mitochondria and synaptosomes isolated from gerbil brain,
      after a 30-min period of graded cerebral ischaemia. These data have been
      correlated with cerebral blood flow (CBF) values as measured by the hydrogen
      clearance technique. Integrated functioning of the mitochondrial respiratory
      chain, using both NAD-linked and FAD-linked substrates, was initially affected at
      CBF values of approximately 35 ml 100 g-1 min-1, and declined further as the CBF
      was reduced. The individual mitochondrial respiratory chain complexes, however,
      showed differences in sensitivity to graded cerebral ischaemia. Complex I
      activities decreased sharply at blood flows below approximately 30 ml 100 g-1 min
      1 (mitochondria and synaptosomes) and complex II-III activities decreased at
      blood flows below 20 ml 100 g-1 min-1 (mitochondria) and 35-30 ml 100 g-1 min-1
      (synaptosomes). Activities declined further as CBF was reduced below these
      levels. Complex V activity was significantly affected only when the blood flow
      was reduced below 15-10 ml 100 g-1 min-1 (mitochondria and synaptosomes). In
      contrast, complex IV activity was unaffected by graded cerebral ischaemia, even
      at very low CBF levels.

PMID- 7722508
TI  - Liposome-mediated gene transfer into normal and dystrophin-deficient mouse
      myoblasts.
AB  - A range of tissue types has now been targeted for development of gene therapeutic
      procedures both to correct genetic defects and to treat acquired disease. In
      particular, skeletal muscle holds great importance, not exclusively for the
      treatment of inherited muscle disorders but also as a platform for the expression
      of heterologous recombinant proteins, destined to immunise the host or to serve
      some systemic therapeutic goal. With respect to the X-linked myopathy Duchenne
      muscular dystrophy (DMD), several gene therapy protocols are being developed that
      focus on complementing primary genetic defects in the DMD gene by introducing
      copies of recombinant gene constructs into muscle cells both ex vivo and in vivo.
      In the present study the potential use of a range of polycationic liposomes as
      physical gene delivery systems for skeletal muscle has been examined. Using a
      LacZ reporter gene under optimised conditions up to 40% transfection efficiencies
      were obtained with the mouse myoblast cell line C2C12. With primary cultures of
      normal and dystrophin-deficient mdx mouse muscle, up to 10% transfection
      efficiency was obtained with reporter gene constructs, and high levels of
      recombinant human dystrophin expression were observed following transfer of
      dystrophin cDNA gene constructs. These in vitro studies indicate that cationic
      liposomes can be used to deliver recombinant genes to muscle cells at high
      efficiency and form a basis to expand investigations into in vivo expression of
      recombinant dystrophin protein either by direct intramuscular gene transfer or
      via implantation of transfected myoblasts.

PMID- 7722509
TI  - A novel cDNA sequence encoding the precursor of the D-amino acid-containing
      neuropeptide fulicin and multiple alpha-amidated neuropeptides from Achatina
      fulica.
AB  - Fulicin (Phe-D-Asn-Glu-Phe-Val-NH2) is an endogenous neuropeptide containing a D
      amino acid from ganglia of the African giant snail Achatina fulica. We have
      cloned a novel cDNA (1,995 nucleotides) encoding a fulicin precursor from the
      snail cerebral and subesophageal ganglia. The fulicin precursor protein (357
      amino acids) contains one copy of fulicin and at least nine other putative alpha
      amidated neuropeptides composed of four to six amino acid residues. Seven of the
      nine neuropeptides were novel, and the other two had the same structures as
      Mytilus inhibitory peptide-related peptides previously isolated from the ganglia
      of Helix pomatia. All sequences of 10 peptides are flanked by Lys-Arg(Lys) at the
      N-terminus and by Gly-Lys-Arg(Lys) at the C-terminus. Nucleotide sequence
      analysis revealed that D-Asn present in fulicin is encoded by the usual L-Asn
      codon (AAT). Although fulicin has as yet only been isolated from the central
      ganglia. RNA blot analysis revealed that single transcripts of approximately 2.0
      kb in size also exist in the ventricles and atria. These results suggest that
      fulicin and related peptides are produced in neurons and the heart by the
      processing of a ribosomally made precursor, although the mechanism of in-chain
      epimerization remains unclear.

PMID- 7722510
TI  - The effect of chronic treatment with the GABA transaminase inhibitors gamma-vinyl
      GABA and ethanolamine-O-sulphate on the in vivo release of GABA from rat
      hippocampus.
AB  - The effects of chronic treatment with the specific, mechanism-based, irreversible
      inhibitors of 4-aminobutyrate aminotransferase (EC 2.6.1.19; GABA transaminase),
      ethanolamine O-sulphate (EOS), and 4-aminohexenoate [vigabatrin; gamma-vinyl-GABA
      (GVG)] on the extracellular concentrations of GABA in the hippocampus have been
      studied using in vivo microdialysis in conscious animals. Oral dosing [3 mg/ml of
      drinking water, giving doses of GVG of 194 +/- 38 mg/kg/day and of EOS of 303 +/-
      42 mg/kg/day (mean +/- SD)] was followed by microdialysis at 2, 8, and 21 days.
      The basal outflow of GABA (in the range of approximately 1-2 pmol/30
      microliters/30-min sample) after 2 and 8 days of treatment was not significantly
      different from that in control animals, but the 21-day treatment gave significant
      rises in the extracellular GABA concentration (up to approximately 6-8 pmol/30
      microliters/30-min sample). Both inhibitors gave similar results. Depolarisation
      with 100 mM K+ gave large increases in GABA release in control (approximately 20
      60 pmol/30 microliters/30-min sample) and treated animals. The 8- and 21-day
      treated animals showed significant increases in the stimulated release compared
      with control animals (approximately 80-100 pmol/30 microliters/30-min sample).
      Excluding Ca2+ had no significant effect on either basal or stimulated release.
      The significant increases in K(+)-evoked release of GABA show that the increased
      intracellular pool of GABA is available for release, and this may be related to
      the anticonvulsant action of these compounds.

PMID- 7722511
TI  - Accumulation of extracellular glutamate by inhibition of its uptake is not
      sufficient for inducing neuronal damage: an in vivo microdialysis study.
AB  - It is well documented that neurons exposed to high concentrations of excitatory
      amino acids, such as glutamate and aspartate, degenerate and die. The clearance
      of these amino acids from the synaptic cleft depends mainly on their transport by
      high-affinity sodium-dependent carriers. Using microdialysis in vivo and HPLC
      analysis, we have studied the effect of the administration of inhibitors of the
      glutamate transporter (L-trans-pyrrolidine-2,4-dicarboxylate and dihydrokainate)
      on the extracellular concentration of endogenous amino acids in the rat striatum.
      In addition, we have analyzed whether the changes observed in the concentration
      of glutamate and aspartate were injurious to striatal cells. Neuronal damage was
      assessed by biochemical determination of choline acetyltransferase and glutamate
      decarboxylase activities, 7 days after the microdialysis procedure. In other
      experiments, pyrrolidine dicarboxylate and dihydrokainate, as well as two other
      inhibitors of the glutamate carrier, DL-threo-beta-hydroxyaspartate and L
      aspartate-beta-hydroxamate, were microinjected into the striatum, and neuronal
      damage was assessed, both biochemically and histologically, 7 or 14 days after
      the injection. Dihydrokainate and pyrrolidine dicarboxylate produced a similar
      remarkable increase in the concentration of extracellular aspartate and
      glutamate. However, the former induced also notable elevations in the
      concentration of other amino acids. Clear neuronal damage was observed only after
      dihydrokainate administration, which was partially prevented by intraperitoneal
      injection of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine
      maleate or by intrastriatal coinjection of 2,3-dihydroxy-6-nitro-7
      sulfamoylbenzo(f)quinoxaline. No cell damage was observed with the other three
      glutamate carrier inhibitors used. It is concluded that an increased
      extracellular glutamate level in vivo due to dysfunction of its transporter is
      not sufficient for inducing neuronal damage. The neurotoxic effects of
      dihydrokainate could be explained by direct activation of glutamate postsynaptic
      receptors, an effect not shared by the other inhibitors used.

PMID- 7722512
TI  - Interaction between adrenergic and peptide stimulation in the rat pineal:
      pituitary adenylate cyclase-activating peptide.
AB  - The 27 amino acid peptide, pituitary adenylate cyclase-activating polypeptide
      (PACAP-27), and its 38 amino acid analogue, PACAP-38, stimulate serotonin-N
      acetyltransferase (NAT) activity and N-acetylserotonin (NAS) and melatonin
      content of pineal glands from adult rats. Maximal stimulation of rat pineal NAT
      by PACAP-38 is not increased further significantly by concurrent stimulation with
      the two related peptides, vasoactive intestinal polypeptide (VIP) and/or peptide
      N-terminal histidine C-terminal isoleucine (PHI). Isoproterenol was a more potent
      inducer of NAT activity than any of these peptides alone or in combination. PACAP
      38 also stimulates melatonin production by chicken pineal cells in culture as
      does VIP. Stimulation by both was not greater than after either alone. Prior
      stimulation of rat pineal NAT activity with VIP, PHI, or PACAP-38 reduces the
      magnitude of subsequent stimulation with PACAP-38 or forskolin. Concurrent
      stimulation of alpha-receptors or treatment with active phorbol ester augments
      rat pineal response to PACAP-38 stimulation just as it increases the response to
      VIP, PHI, and beta-receptor stimulation. Pineals from newborn rats respond to
      PACAP-38 with an increase in NAT activity and the increase is augmented by
      concomitant alpha 1-adrenergic stimulation. The putative PACAP inhibitor PACAP (6
      38) and the putative VIP inhibitor (Ac-Tyr,D-Phe)-GRF 1-29 amide, in 100-1,000
      fold excess, did not affect the stimulatory activity of any of the peptides.
      Pineal melatonin concentration parallels changes in pineal NAT activity.

PMID- 7722513
TI  - Antibodies to a segment of tyrosine hydroxylase phosphorylated at serine 40.
AB  - A synthetic peptide corresponding to residues 32-47 of rat tyrosine hydroxylase
      (TH) was phosphorylated by protein kinase A at Ser40 and used to generate
      antibodies in rabbits. Reactivity of the anti-pTH32-47 antibodies with phospho-
      and dephospho-Ser40 forms of TH protein and peptide TH32-47 was compared with
      reactivity of antibodies to nonphosphorylated peptide and to native TH protein.
      In antibody-capture ELISAs, anti-pTH32-47 was more reactive with the phospho-TH
      than with the dephospho-TH forms. Conversely, antibodies against the
      nonphosphorylated peptide reacted preferentially with the dephospho-TH forms. In
      western blots, labeling of the approximately 60-kDa TH band by anti-pTH32-47 was
      readily detectable in lanes containing protein kinase A-phosphorylated native TH
      at 10-100 ng/lane. In blots of supernatants prepared from striatal synaptosomes,
      addition of a phosphatase inhibitor was necessary to discern labeling of the TH
      band with anti-pTH32-47. Similarly, anti-pTH32-47 failed to immunoprecipitate TH
      activity from supernatants prepared from untreated tissues, whereas prior
      treatment with either 8-bromoadenosine 3',5'-cyclic monophosphate or forskolin
      enabled removal of TH activity by anti-pTH32-47. Lastly, in immunohistochemical
      studies, anti-pTH32-47 selectively labeled catecholaminergic cells in tissue
      sections from perfusion-fixed rat brain.

PMID- 7722514
TI  - N-cadherin is a major glycoprotein component of isolated rat forebrain
      postsynaptic densities.
AB  - We have previously described a monoclonal antibody, PAC 1, that recognises two
      postsynaptic density (PSD)-enriched glycoproteins (pgps) of apparent M(r) 130,000
      (pgp130) and 117,000 (pgp117). Immunodevelopment of western blots of rat
      forebrain homogenate, synaptic membrane (SM), and PSD samples with PAC 1 and an N
      cadherin antiserum shows that pgp130 and N-cadherin are of identical apparent
      M(r) and show identical patterns of enrichment in these fractions. The apparent
      molecular masses of pgp130 and N-cadherin are both lowered by 11 kDa following
      removal of N-linked carbohydrate with endoglycosidase-F containing N
      glycopeptidase. The two molecules show an identical pattern of migration when
      separated by two-dimensional electrophoresis. A single 130-kDa band
      immunoprecipitated from solubilised PSD preparations by the N-cadherin antiserum
      is recognised by PAC 1 on western blots. We conclude that pgp130 is N-cadherin.
      Development of western blots of two-dimensional gel separations of SM and PSD
      glycoproteins shows that N-cadherin is a major glycoprotein component of PSDs.
      The immunoprecipitation experiments show that the M(r) of N-cadherin is greater
      than that of the major pgp, PSD gp116. The PAC 1 antibody recognises two
      concanavalin A-binding glycoproteins with apparent molecular masses of 136 and
      127 kDa in liver samples. The 136-kDa band is also recognised by the N-cadherin
      antiserum. These observations, together with data showing that the PAC 1 epitope
      is intracellular, suggest that PAC 1 is a pan-cadherin antibody and recognises an
      epitope on the conserved cadherin intracellular carboxyl-terminal domain.

PMID- 7722515
TI  - Regulation of sialyltransferase activities by phosphorylation and
      dephosphorylation.
AB  - The composition of tissue gangliosides is thought to result mainly from the
      active regulation and selective expression of specific enzymes responsible for
      their metabolism. In the last few years, we have purified several rat brain
      sialyltransferases to homogeneity; the availability of these highly purified
      enzymes enabled us to investigate their regulation and expression at the
      molecular level. Thus, we studied the regulation of sialyltransferase activities,
      in particular, CMP-NeuAc:GM1 and CMP-NeuAc:LacCer sialyltransferases by a
      phosphorylation/dephosphorylation mechanism. Protein kinase C was added to a
      standard enzyme assay mixture containing [gamma-32P]ATP, and the activity of the
      enzyme was measured after various incubation times. We found that treatment of
      several sialyltransferases by protein kinase C decreased their activities in a
      time-dependent manner. Analyses of 32P-labeled amino acids revealed that the
      major phosphorylation site of CMP-NeuAc:GM1 alpha 2-->3 sialyltransferase (ST-IV)
      was serine and that for CMP-NeuAc:LacCer alpha 2-->3 sialyltransferase (ST-I) was
      primarily threonine. Partial recovery of the enzyme activity could be achieved by
      treatment of the phosphorylated sialyltransferases with rat brain protein
      phosphatase. We conclude that the activities of sialyltransferases can be
      modulated by protein kinase C and protein phosphatase and this may represent a
      potential regulatory mechanism for ganglioside biosynthesis.

PMID- 7722516
TI  - 7B2 is a specific intracellular binding protein of the prohormone convertase PC2.
AB  - Biosynthetic pulse-chase analyses have previously demonstrated that the
      prohormone convertase PC2 is first synthesized as a precursor pro-PC2 and that
      zymogen activation to PC2 occurs following the slow exit of pro-PC2 from the
      endoplasmic reticulum (ER) and its concentration within the trans-Golgi network
      (TGN). The endocrine and neural protein 7B2 is first synthesized as a
      nonglycosylated precursor (pro-7B2), which is cleaved within the TGN by a furin
      like ubiquitous convertase at the RRKRR155S site to generate 7B2. In this report,
      we demonstrate that within the ER, pro-7B2 binds pro-PC2 but not any of the other
      convertases furin, PC1, PACE4, or PC5. This specific binding is Ca2+ dependent
      and does not require an N-glycosylated pro-PC2. Mutagenesis of the RRKRRS
      sequence demonstrated that the intact hexapeptide is critical for this binding,
      because the latter was abolished by mutations of the RR152 and greatly diminished
      by mutations of either the R151 or S156 residues of pro-7B2. Once the complex is
      formed in the ER, it is then transported to the TGN where furin or a furin-like
      convertase cleaves both precursors, even when present as a complex. We also
      provide evidence that following zymogen cleavage, 7B2 remains bound to PC2,
      suggesting the presence of at least one other Ca(2+)-dependent binding site
      within the 7B2 sequence. Coexpression of 7B2 and PC2, although resulting in an
      elevation of the level of pro-PC2, did not eliminate the processing of pro-PC2 to
      PC2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722517
TI  - Immunocytochemical examination of neural rat and mouse primary cultures using
      monoclonal antibodies raised against pyruvate carboxylase.
AB  - Pyruvate carboxylase (EC 6.4.1.1; PC) catalyzes the formation of oxaloacetate by
      energy-dependent fixation of CO2 to pyruvate. The aim of the present work was to
      generate antibodies against PC and use them to localize PC in the cells of
      astroglia-rich and neuron-rich primary cultures derived from the brains of rats
      and mice. Mouse monoclonal antibodies raised against the enzyme were shown to be
      monospecific as indicated by immunoblotting. The staining of the cells for PC
      appeared in grains. These represent mitochondria, as PC is known as a
      mitochondrial enzyme. Immunocytochemical examination of astroglia-rich primary
      cultures of rat or mouse brain cells revealed a colocalization of PC with the
      astroglial marker glial fibrillary acidic protein (GFAP) in many cells. However,
      there were GFAP-positive cells showing no specific staining for PC, and vice
      versa. Also, in neuron-rich primary cultures PC was found only in the
      approximately 10% GFAP-expressing astroglial cells contaminating the neuron-rich
      primary culture, whereas it was absent from the neurons identified by antibodies
      against neuron-specific enolase. These results suggest that PC is predominantly
      an astroglial enzyme and that astroglial cells play an important role in the
      intermediary and the energy metabolism of the brain.

PMID- 7722518
TI  - Regulation of endogenous ADP-ribosylation by acute and chronic lithium in rat
      brain.
AB  - In the present study, we investigated the effects of lithium on endogenous ADP
      ribosylation in rat brain. It was found that addition of lithium in vitro
      inhibits endogenous ADP-ribosylation activity in extracts of frontal cortex at
      therapeutically relevant concentrations. Inhibition is observed at concentrations
      as low as 0.3 mM and is maximal at 1 mM when 50% inhibition is obtained. A
      similar degree of inhibition of endogenous ADP-ribosylation was observed for all
      substrate proteins identified, including Gs alpha, suggesting that lithium's
      effect may be achieved at the level of ADP-ribosyltransferases and not specific
      substrate proteins. In contrast to lithium, chloride salts of sodium and
      potassium do not alter endogenous ADP-ribosylation activity in frontal cortex. To
      assess the possible in vivo relevance of this in vitro action of lithium, we
      studied the effect of chronic lithium administration on levels of endogenous ADP
      ribosylation in frontal cortex. It was found that chronic lithium treatment, in
      contrast to the inhibitory effect of the drug in vitro, produced a > 35% increase
      in endogenous ADP-ribosylation activity. A similar degree of increase was
      observed for all of the substrate proteins identified. These novel findings raise
      the possibility that certain endogenous ADP-ribosyltransferases are among the
      acute targets of lithium in the brain and that adaptations in these enzymes may
      be part of the mechanisms underlying lithium's long-term effects on brain
      function.

PMID- 7722519
TI  - Nondestructive measurement of retinal glucose transport and consumption in vivo
      using NMR spectroscopy.
AB  - The cellular events underlying various retinopathies are poorly understood but
      likely involve perturbation of retinal glucose metabolism. Current methods for
      assessing this metabolism are destructive, thus limiting longitudinal studies. We
      hypothesize that following an intravitreous injection, the clearance rate of a
      glucose analogue will be a nondestructive index of retinal glucose transport and
      metabolism in vivo. First, radiolabeled glucose analogues were injected into the
      vitreous. After 40 min, the dominant clearance path was posterior via the retina
      and was consistent with a facilitated transport mechanism. Next, either [6,6
      2H2]glucose or 3-deoxy-3-fluoro-D-glucose was injected into the vitreous of
      rabbit eyes, and the clearance rate of each analogue was determined over 40 min
      using, respectively, 2H or 19F NMR. These rates were interpreted as a function of
      the retinal glucose transport and consumption. From the NMR data, the rate of
      retinal glucose consumption was approximately 16 times slower than the transport
      of glucose. These data demonstrate that NMR measurements of glucose analogue
      clearance rate from the vitreous can provide a nondestructive index of retinal
      glucose transport and consumption in vivo.

PMID- 7722520
TI  - Novel reticular calcium binding protein is purified on taipoxin columns.
AB  - We identified, by affinity chromatography, two putative binding proteins for the
      presynaptic snake venom toxin taipoxin. We have previously characterized one of
      these proteins [neuronal pentraxin (NP)] as a neuronally secreted protein with
      homology to acute-phase proteins. Here we report the identification of the second
      protein as a 49-kDa lumenal calcium binding protein that we have named taipoxin
      associated calcium binding protein 49 (TCBP-49). This protein contains six EF
      hand putative calcium binding domains and the carboxyl-terminal sequence His-Asp
      Glu-Leu (HDEL), identical to the yeast endoplasmic reticulum retention signal.
      Message for this protein is present in brain, liver, muscle, heart, kidney, and
      testis. Antibodies to this protein label reticular organelles of neurons and
      glia. This localization and the specific enrichment of native and recombinant
      TCBP-49 on columns of immobilized taipoxin raise the possibility that this
      protein interacts with internalized taipoxin, perhaps mediating its activation.
      The availability of pure TCBP-49 will allow direct tests of whether TCBP-49
      alters the integrity of the oligomeric structure, phospholipase activity, or
      toxicity of taipoxin.

PMID- 7722521
TI  - Purification, properties, and specificity of rat brain cytosolic fatty acyl
      coenzyme A hydrolase.
AB  - Rat brain cytosolic acyl-CoA hydrolase has been purified 3,500-fold to apparent
      homogeneity using heat treatment, ammonium sulfate fractionation followed by
      anion exchange, hydrophobic interaction, and hydroxyapatite c chromatography. The
      purified enzyme remains stable only in the presence of a high concentration (30%,
      vol/vol) of ethylene glycol. On sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis the purified enzyme shows a single band of 40.9 kDa. However, on
      high-performance size-exclusion chromatography the migration rate of the enzyme
      corresponds with an apparent molecular mass of 148 kDa, indicating that the
      native enzyme may be a tetramer. The enzyme catalyzes the hydrolysis of fatty
      acyl-CoAs from six to 18 carbon chains long, having the highest activity for
      lauroyl (12:0)-CoA. For the purified enzyme the Km for palmitoyl-CoA is 5.8
      microM and the Vmax is 1,300 mumol/min/mg of protein. The enzyme is inhibited by
      bovine serum albumin, various detergents, lysophosphatidylcholine, and palmitoyl
      carnitine. Among the sulfhydryl agents, only p-hydroxymercuribenzoate inhibited
      the enzyme. The enzyme is also inactivated by treatment with a high concentration
      of diethyl pyrocarbonate, an active center histidine-reacting agent, but not by
      phenylmethylsulfonyl fluoride (10 mM), a serine esterase inhibitor. The purified
      enzyme does not appear to possess any O-ester hydrolase, lysophospholipase,
      transacylase, or acyltransferase activity.

PMID- 7722522
TI  - Exposure to an antisense oligonucleotide decreases corticotropin-releasing factor
      receptor binding in rat pituitary cultures.
AB  - Corticotropin-releasing factor (CRF) appears to integrate the endocrine,
      autonomic, immunologic, and behavioral responses of mammals to stress. To
      investigate further the role of CRF in the CNS, we have begun investigating the
      usefulness of "antisense knockdown" strategies directed against the CRF receptor
      using rat anterior pituitary gland primary cell cultures. The 15-mer antisense
      (5' CTG-CGG-GCG-CCG-TCC 3') and "scrambled" control (5' CGT-CCG-CGC-GCT-GCG 3')
      oligonucleotides were synthesized based on the rat CRF receptor sequence just
      downstream of the initiation codon. In each of four separate experiments,
      exposure to 10 mumol/L of antisense oligonucleotide for 40-67 h resulted in
      significant (17-36%) decreases in 125I-ovine CRF binding to pituitary cells as
      compared with either control (no oligonucleotide) or 10 mumol/L of "scrambled"
      oligonucleotide. Moreover, compared with scrambled oligonucleotide, exposure to
      10 mumol/L of antisense oligonucleotide, which produced a 22% decrease in CRF
      receptor binding, also resulted in a significant attenuation of the
      adrenocorticotrophic hormone response following a 30-min challenge with 100
      pmol/L of CRF. Thus, CRF receptor antisense oligonucleotides apparently reduce
      functional expression of CRF receptors. This technique may be useful in studying
      the kinetics of CRF receptor production and the physiological functions of CRF
      receptors within the CNS.

PMID- 7722523
TI  - Superoxide dismutase concentration and activity in familial amyotrophic lateral
      sclerosis.
AB  - Some cases of autosomal-dominant familial amyotrophic lateral sclerosis (FALS)
      have been associated with mutations in SOD1, the gene that encodes Cu/Zn
      superoxide dismutase (Cu/Zn SOD). We determined the concentrations (microgram of
      Cu/Zn SOD/mg of total protein), specific activities (U/microgram of total
      protein), and apparent turnover numbers (U/mumol of Cu/Zn SOD) of Cu/Zn SOD in
      erythrocyte lysates from patients with known SOD1 mutations. We also measured the
      concentrations and activities of Cu/Zn SOD in FALS patients with no identifiable
      SOD1 mutations, sporadic ALS (SALS) patients, and patients with other neurologic
      disorders. The concentration and specific activity of Cu/Zn SOD were decreased in
      all patients with SOD1 mutations, with mean reductions of 51 and 46%,
      respectively, relative to controls. In contrast, the apparent turnover number of
      the enzyme was not altered in these patients. For the six mutations studied,
      there was no correlation between enzyme concentration or specific activity and
      disease severity, expressed as either duration of disease or age of onset. No
      significant alterations in the concentration, specific activity, or apparent
      turnover number of Cu/Zn SOD were detected in the FALS patients with no
      identifiable SOD1 mutations, SALS patients, or patients with other neurologic
      disorders. That Cu/Zn SOD concentration and specific activity are equivalently
      reduced in erythrocytes from patients with SOD1 mutations suggests that mutant
      Cu/Zn SOD is unstable in these cells. That concentration and specific activity do
      not correlate with disease severity suggests that an altered, novel function of
      the enzyme, rather than reduction of its dismutase activity, may be responsible
      for the pathogenesis of FALS.

PMID- 7722524
TI  - Increased expression of retinal TIMP3 mRNA in simplex retinitis pigmentosa is
      localized to photoreceptor-retaining regions.
AB  - The human tissue inhibitor of metalloproteinases-3 (TIMP3) gene is the most
      recently characterized member of a family of genes whose products are implicated
      in extracellular matrix (ECM) remodelling. We previously described an increase in
      expression of TIMP3 mRNA in retinas affected by the progressive photoreceptor
      degenerative disease, simplex retinitis pigmentosa (RP). To gain further insight
      into the association between TIMP3 overexpression and retinal degeneration, we
      have analyzed the cellular localization of TIMP3 mRNA in control and simplex RP
      retinas using in situ hybridization. No TIMP3 mRNA expression was detectable in
      control neural retina. IN RP-affected retinas, overexpression of TIMP3 mRNA was
      observed in photoreceptor inner segments and in the ganglion cell layer only in
      those regions retaining relatively nondystrophic retinal architecture. Modulation
      of TIMP3 expression in these regions, possibly in association with matrix
      metalloproteinases, may reflect remodelling of the retinal ECM and concomitant
      reorganization of neuronal connectivity.

PMID- 7722525
TI  - Activation of arc, a putative "effector" immediate early gene, by cocaine in rat
      brain.
AB  - As immediate early genes (IEGs) are thought to play a critical role in mediating
      stimulus-induced neuronal plasticity, several laboratories have characterized the
      IEG response induced by cocaine to help define the changes in gene expression
      that may underlie its long-lasting behavioral effects. Although activation of
      several transcription factor IEGs has been described, little is known about which
      "effector" IEGs, if any, are also induced. In the present study, we have examined
      whether cocaine administration affects expression of a recently identified
      "effector" IEG, referred to as arc (activity-regulated, cytoskeleton-associated).
      This IEG encodes a protein with homology to spectrin that appears to be
      associated with the actin cytoskeleton. Using in situ hybridization, we have
      found that systemic cocaine administration elicits a robust, transient rise in
      arc mRNA levels in striatum, which is suppressed by D1 dopamine receptor
      blockade, reserpine treatment, or striatal 6-hydroxydopamine lesions. D2 receptor
      antagonist triggered arc expression when administered alone. Immunohistochemical
      studies indicated that Arc protein induced by cocaine is expressed in neuronal
      cell bodies and dendrites. As Arc appears to be component of the neuronal
      cytoskeleton, it may be involved in structural alterations underlying neuronal
      plasticity triggered by cocaine.

PMID- 7722526
TI  - The role of the basal ganglia in motor control: contributions from PET.
AB  - This article reviews PET activation data on basal ganglia function that have been
      reported in association with performance of different motor tasks by normal
      subjects and movement disorder patients. PET findings are contrasted with
      electrophysiological observations both in man and in non-human primates and with
      observations on clinical and cognitive function of movement disorder patients.
      Possible roles that the basal ganglia may play in motor control are discussed in
      the light of these data.

PMID- 7722527
TI  - Immunofluorescence study of immune complexes in polymyalgia rheumatica.
AB  - Two elderly patients with polymyalgia rheumatica (PMR), one with and the other
      without temporal arteritis (TA), are presented. Immunofluorescence study of
      muscle biopsy specimens showed IgG, IgA, and fibrinogen deposits in the
      perifascicular area in the perimysium. This finding suggests that immune
      complexes play a role in the pathogenesis of this condition and that the
      pathophysiology of PMR involves an interstitial inflammatory process.

PMID- 7722528
TI  - Value of brain CT scan in children with febrile convulsions.
AB  - Studies specifically dealing with the value of brain CT scans in different types
      of febrile convulsion are lacking when compared to the large amount of studies on
      other favorable convulsive disorders. This study is correlation study between
      children who presented with febrile convulsions (n = 38) and the results of their
      brain CT scans. Twenty four patients had risk factors for subsequent epilepsy
      (group A), 3 of them had abnormal CT scans in the form of mild diffuse brain
      atrophy, and all 3 patients were found to have prior neurodevelopmental deficits.
      The other 14 patients did not have such risk factors (group B) and had normal
      brain CT scans. Despite the small size of the study, the results are unequivocal,
      and it can be concluded that brain CT scan is not indicated in the management of
      simple or complex febrile convulsions. Brain CT may be justifiable, but may not
      be clinically useful in the management of febrile convulsion patients with prior
      neurodevelopmental deficits.

PMID- 7722529
TI  - Absence of human retroviral antibodies in epidemic neuropathy in Cuba: report of
      the first two cases of HTLV-I-associated tropical spastic paraparesis observed in
      Cuba.

PMID- 7722530
TI  - New fiber formation in rat soleus muscle following administration of denervated
      muscle extract.
AB  - A study was made of Wistar rat soleus muscle following intraperitoneal
      administration of denervated muscle extract over 1 and 2 days. Light microscopy
      revealed the appearance on fiber surfaces of basophilic satellite structures
      whose histochemical behaviour differed from that of the parent fiber. Small
      fibers showing regenerative characteristics were also detected, mainly in the
      extrafascicular spaces. At ultrastructural examination, activated satellite cells
      were visible, and there was evidence of splitting in subsarcolemmal regions of
      apparently hypertrophic muscle fibers. Interstitial cells were occasionally
      observed, containing structures like myofilaments. The hypothesis is advanced
      that denervated muscle extract contains substances able to stimulate new fiber
      formation in adult skeletal muscle.

PMID- 7722531
TI  - High dose methylprednisolone therapy reduces expression of JE/MCP-1 mRNA and
      macrophage accumulation in the ischemic rat brain.
AB  - The effects of glucocorticoid (GC) on ischemic brain remain to be investigated.
      Since GC modulates immunological system, it also may inhibit macrophage
      accumulation in the ischemic brain. The GC effect, if any, on macrophages in
      ischemic brain, may be mediated through modulation of JE/MCP-1 gene, a strong
      monocyte attractant, which is expressed in the rat brain after ischemia. The
      purpose of the present study is to elucidate the effect of high dose
      methylprednisolone (MP) treatment on (1) macrophage infiltration, (2)
      histopathology of the ischemic lesion, and (3) expression of JE/MCP-1 mRNA, in a
      focal cerebral ischemia model of the rat. Thirty Wistar rats were used in this
      study. Focal cerebral ischemia was induced by advancing a nylon monofilament into
      the internal carotid artery until the origin of the middle cerebral artery (MCA)
      was occluded. For JE/MCP-1 mRNA study, animals (n = 9) were randomly injected
      with MP 75 mg/kg (x 3) (n = 3), 100 mg/kg (x 3) (n = 3), or same volume of saline
      (n = 3) and killed 24 h after onset of MCA occlusion. Three animals were used as
      a normal control, and a section of the liver from one rat was used as an internal
      control for JE/MCP-1 mRNA. Northern blot analysis was performed using murine JE c
      DNA. For the histopathological study, animals (n = 17) were randomly divided into
      a MP group (MP 100 mg/kg x 3, n = 9) and a control group (saline treated, n = 8),
      and killed 72 h after onset of MCA occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722532
TI  - Connective tissue proliferation and growth factors in animal models of Duchenne
      muscular dystrophy.
AB  - The difference in the lifespan of dy and mdx mice could be due to different
      muscle regeneration capabilities. In mdx an involvement of bFGF in stimulating
      regeneration has been postulated. The aim of our work was to detect the presence,
      and to study the distribution, of muscular and connective tissue growth factors
      in mdx and dy mice at different stages of muscle pathology. From 7 to 10 weeks of
      age the difference between the two dystrophic mice becomes evident. At 13 weeks
      the dy mouse presents a predominance of fibrosis and degenerative muscular
      phenomena while the main pathological feature in mdx mouse is the muscle
      regeneration. In both animal models fibrosis proliferation is correlated to the
      presence of EGF and its receptor and TGF beta 1. bFGF was localized to
      regenerating and degenerating fibers in both dy and mdx mice. The bFGF presented
      a normal pattern in mdx mice at 20 weeks when regenerative and degenerative
      phenomena were no longer present. Our data suggest that growth factors could
      influence the outcome of muscular regenerative and degenerative processes.

PMID- 7722533
TI  - Adhesive glycoproteins CD11a and CD18 are upregulated in the leukocytes from
      patients with ischemic stroke and transient ischemic attacks.
AB  - Leukocytes may have an important role in the pathogenesis of brain injury after
      ischemia. Expression of adhesion molecules on leukocytes and/or endothelia is
      needed for leukocytes to adhere to endothelia and infiltrate into the injured
      brain. The purpose of the present pilot study is to delineate whether the
      expression of leukocyte adhesion molecules, CD11a and CD18, are upregulated in
      patients with ischemic stroke and transient ischemic attack. Ten patients with
      ischemic stroke, 6 with transient ischemic attack (TIA), and 11 age and risk
      factor matched controls were studied. Using immunofluorescence phenotyping and
      flow cytometry, leukocyte membrane expression of CD11a and CD18 were measured
      within 72 h after onset of ischemia. Follow-up measurements were performed at 5-7
      days after ictus in 6 patients with stroke, and at 3-5 days after ictus in 3
      patients with TIA. CD11a immunofluorescence (IF) was significantly increased
      within 72 h after onset of symptoms in patients with stroke as well as TIA
      compared with the control group (p < 0.017). IF of CD18 also increased in both
      patient groups, but significance was reached only in the TIA group (p < 0.05). No
      difference of CD11a and CD18 IF was detected between stroke and TIA groups.
      Follow-up measurement of CD11a and CD18 showed a trend of decrease, but CD11a IF
      remained significantly elevated compared with the control group (p < 0.017).
      Expression of leukocyte adhesion molecules CD11a, and CD18 are upregulated in
      patients with ischemic stroke and TIA. Although these data are preliminary, our
      data suggest that these molecules are associated with cerebrovascular disorders
      including ischemic stroke and TIA.

PMID- 7722534
TI  - Contralateral early blink reflex in patients with HTLV-I associated
      myelopathy/tropical spastic paraparesis.
AB  - Thirty-two Japanese patients with HTLV-I-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) were studied by means of the electrically elicited blink
      reflex and three responses (R1, R2, R3) were registered. 69% of the patients
      displayed a uni- or bilateral crossed R1 response (R1k) as compared to 11% in the
      control group. A positive correlation between R1k and an exaggerated jaw jerk
      reflex was found in the patients. Central abnormalities of the nervous system
      with diminished presynaptic inhibition acting in the interneuronal input of the
      brainstem of HAM/TSP patients was the most likely cause. It could lead to the
      unmasking of crossed trigemino-facial pathway reflex which is present in the
      normal population from birth. These results strongly support the supraspinal
      involvement of the central nervous system (CNS) in HAM/TSP more than usually
      thought.

PMID- 7722535
TI  - Fatal reducing body myopathy. Ultrastructural and immunohistochemical
      observations.
AB  - Two female infants who developed normally during infancy began to have
      progressive muscle hypotonia and weakness from 2 years 10 months and 2 years 3
      months of ages, respectively. Both patients had rapidly progressive muscle
      weakness with death from respiratory failure at 4 years 11 months and 3 years 9
      months, respectively. In addition to mild inflammation in their muscle biopsies,
      the most striking finding was the presence of numerous reducing bodies (RB) in
      almost all degenerating fibers. By electron microscopy, these bodies consisted of
      fine granular material, usually located around the degenerating nucleus. These
      bodies showed no immunohistochemical reaction to antibodies against structural,
      cytoskeletal and membrane proteins and a histone-specific antibody against nuclei
      and chromosomes. They were occasionally positively stained with a ubiquitin
      antibody. Although the origin of these bodies remains unknown, they appeared to
      be related to active myofibrillar degeneration, probably resulting from primary
      nuclear degeneration.

PMID- 7722536
TI  - Non-progressive familial congenital cerebellar hypoplasia.
AB  - A syndrome is reported of congenital non-progressive, gradually slightly
      improving, ataxia in 3 out of 5 male sibs, issues of a first-order consanguineous
      mating. Additional characteristic features included: moderate microcephaly,
      generalised muscle weakness and hypotonia, nystagmus, and moderate mental
      retardation. A pyramidal syndrome of hyperreflexia and Babinski signs, without
      any spasticity, became manifest in the 2nd or 3rd year of life. In all three, the
      caudal part of the vermis was absent, the enlarged IVth ventricle opening up via
      Magendie's foramen into the cisterna magna. The middle and rostral vermian parts
      as well as the sagittal paravermian parts of the cerebellar hemispheres were
      hypoplastic. The differential diagnosis of this syndrome is analysed and the
      developmental pathogenetic mechanisms likely to produce the typifying
      distribution of aplasia are indicated.

PMID- 7722537
TI  - Second messenger systems in Tourette's syndrome.
AB  - Abnormalities within second messenger systems have been hypothesized as the
      underlying pathophysiologic mechanism in a variety of neuropsychiatric disorders.
      In the Gilles de la Tourette syndrome (TS) prior studies have shown that the
      concentration of adenosine 3',5'-monophosphate (cAMP) is reduced in cortical and
      putamen brain regions. In this study, postmortem cortical tissues from 4 adults
      (mean age 59.5 years) with the lifetime diagnosis of TS and 5 controls (mean age
      63.8 years) were analyzed for functional activities within the cAMP and
      phosphoinositide systems. In addition, plasma cAMP was quantified in children
      with TS (n = 33) and controls (n = 17). In frontal (A4, A6) and occipital (A17)
      cortical tissues there were no significant differences for adenylyl cyclase
      activity whether assayed under basal conditions or after stimulation with GTP
      gamma S (a non-hydrolyzable GTP analog), forskolin (a selective enzyme
      stimulator), or (-)-isoproterenol (a beta-adrenergic agonist). D2 receptor
      activation (quinpirole) and assessment of the inhibitory guanine nucleotide
      protein also showed no significant alterations in TS samples. Activity of cAMP
      phosphodiesterase was increased insignificantly in A4 and A17 TS brain regions.
      Plasma concentrations of cAMP in plasma were similar in children with TS (135.4
      +/- 8.3 pmol/ml) and controls (132.6 +/- 7.9 pmol/ml). Postmortem membrane
      receptor binding for markers within the phosphoinositide (PI) system showed that
      TS samples had increased [3H]phorbol ester binding to protein kinase C sites in
      area A17, but normal binding in A4. In contrast, [3H] inositol 1,4,5-triphosphate
      binding to IP3 receptors showed no significant changes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7722538
TI  - Myophosphorylase deficiency affects muscle mitochondrial respiration as shown by
      31P-MR spectroscopy in a case with associated multifocal encephalopathy.
AB  - We report here a glycogen storage myopathy type V associated with multifocal
      encephalopathy. The patient, a 43-year-old male with increased serum CK, a heavy
      drinker and smoker, had been affected by generalized epilepsy since age 24, after
      a cranial injury. He had had a right hemiparesis 2 years before coming to our
      observation and a transient left hemiparesis the following year. CT and MRI of
      the brain showed multiple hemispheric lesions consistent with an ischemic
      process, as suggested by single photon emission tomography of the brain. Muscle
      biopsy showed a vacuolar myopathy, and myophosphorylase activity was 13% of the
      normal mean. Phosphorus magnetic resonance spectroscopy (31P-MRS) performed on
      resting calf muscles showed increased PCr to ATP and decreased PCr to P(i)
      ratios. During both aerobic and ischemic exercise 31P-MRS failed to show any
      cytosolic acidification and phosphomonoesters (PME) accumulation, two MRS
      findings in agreement with McArdle's syndrome diagnosis. Mitochondrial
      respiration was also affected as shown by a low PCr to P(i) ratio at rest and by
      a low rate of PCr re-synthesis during recovery from aerobic exercise. This latter
      finding in McArdle's disease can be explained by decreased mitochondrial
      substrate availability, which in turn can contribute to the phenotypic
      manifestations of the disease.

PMID- 7722539
TI  - The sympathetic skin response in reflex sympathetic dystrophy.
AB  - The sympathetic skin response (SSR) was examined in 12 consecutive patients with
      reflex sympathetic dystrophy (RSD). It was normal in the involved limbs of five
      patients, of lower amplitude than on the contralateral side in three and absent
      only on the involved side in four. The response abnormality was more prominent in
      patients examined during the first year following the injury. These abnormalities
      could reflect either the peripheral injury underlying RSD or secondary central
      nervous system disturbances.

PMID- 7722540
TI  - Serum anti-brain endothelium antibodies and cognitive assessment in patients with
      Binswanger's encephalopathy.
AB  - The pathogenic mechanism underlying the vascular changes in Binswanger's
      encephalopathy (BE) is unknown. To test whether alterations of the humoral
      immunity may lead to endothelium damage, we analyzed serum levels of anti-brain
      endothelium antibodies (ABEA) (IgG and IgM) in 16 BE patients, 19 subjects with
      ischemic vascular disease without mental deterioration and 18 normal healthy
      subjects. ABEA IgM were found elevated in 1/16 (6%) BE patients and in 4/19 (21%)
      patients with cerebrovascular diseases; an increase in ABEA IgG was found in 6/16
      (38%) BE patients and in 7/19 (37%) cerebrovascular patients. Association with
      anti-cardiolipin antibodies (IgG and/or IgM) was found in 50% of BE patients with
      elevated ABEA and only 10% of those with no increase, whereas high titres of anti
      neurofilament antibodies (1:10,000) were detected in 40% and 71% respectively. In
      BE, ABEA IgG but not IgM showed a trend, although not significant, towards a
      correlation with the duration of the disease (rs = 0.47; p = 0.07) and
      significantly correlated with the cognitive function as assessed by the Mini
      mental state (MMS) score (rs = 0.56; p = 0.02). Higher mean values of the MMS
      score were found in BE patients with elevated ABEA than in those without (p =
      0.04). This difference was not due to language disorders neither to an
      association with stroke risk factors or anti-neurofilament antibodies. However,
      there were no significant differences in MMS scores between cerebrovascular
      patients with ABEA and those without. A "neuro-protective" role is hypothesized
      for the ABEA in the development of dementia in BE.

PMID- 7722541
TI  - Clustering and six year cluster-tracking of serum total cholesterol, HDL
      cholesterol and diastolic blood pressure in children and young adults. The
      Cardiovascular Risk in Young Finns Study.
AB  - Clustering and tracking of serum total cholesterol, high-density lipoprotein
      cholesterol (HDL-C) and diastolic blood pressure were studied in children and
      young adults. "High-risk" individuals were defined as those having these risk
      factors at the age and sex specific upper tertile (lowest tertile for HDL-C).
      Among older boys risk factors occurred at adverse levels more often than expected
      by chance. Cluster-tracking was assessed as the probability of remaining in the
      extreme tertiles during follow-up. Approximately 25% of subjects initially at
      "risk" remained there for 6 years. Subjects who became high-risk individuals
      during the follow-up expressed greater increase in obesity indices, started to
      consume more saturated fat and cholesterol and became physically active less
      often compared to those subjects who were initially at risk, but no longer at the
      follow-up.

PMID- 7722542
TI  - The prevalence of Helicobacter pylori positivity in a symptom-free population,
      aged 1 to 40 years.
AB  - Epidemiologic data about the prevalence of Helicobacter pylori positivity as
      determined by serology are presented in a large series of asymptomatic subjects
      (n = 1046). Serology is nowadays generally accepted as a valid non-invasive
      screening method for the detection of a Helicobacter pylori infection. Blood
      samples were taken from apparently healthy children (n = 480; aged 1-17 years)
      and pregnant women (n = 566; age 18-40 years) who were admitted for routine pre
      surgery or pre-natal blood analysis. 162 (15.5%) had a positive titer for
      Helicobacter pylori. There was a significant increase in the number of positive
      patients with increasing age (ranging from 6.2% in the age group of the 1-5 years
      old to 31.0% in the age group of the 36-40 years old (p < 0.01). The meaning of
      this relatively high prevalence of "asymptomatic carriers" remains to be
      evaluated. A long-term follow-up of these patients should be considered to
      evaluate if they will develop clinical manifestations suggestive for Helicobacter
      pylori infection.

PMID- 7722543
TI  - Measuring changes in logarithmic data, with special reference to bronchial
      responsiveness.
AB  - Bronchial provocation tests with agents such as histamine and methacholine are
      commonly used in clinical and epidemiological studies of respiratory illness
      because bronchial hyperresponsiveness is a non-specific abnormality of the
      airways which is characteristic of asthma. However, measurements of bronchial
      responsiveness are log-normally distributed. As a result, special considerations
      need to be given to reporting within-subject changes in these measurements in
      longitudinal studies as, for example, in clinical trials or in any study in which
      a before-and-after experimental design is used. In these types of experiments,
      changes in bronchial responsiveness should not be simply expressed in the units
      of the measurement, such as dose of provoking agent, but must be expressed in
      units based on a logarithmic scale. The appropriate log-based units for measuring
      within-subject changes are doubling dose, fold difference or percent change. This
      paper explains the methods for calculating changes in these units in a
      statistically correct manner. All three units represent different ways of
      expressing the same change on a logarithmic scale. However, 'doubling dose' is
      only appropriate when it relates directly to the method of administering the
      provoking agent in doubling concentrations and 'fold difference' or 'percent
      change' are both appropriate for expressing any log-based changes. The methods
      for calculating changes in these units also apply to calculations of
      repeatability within test methods and to calculations of comparability and
      agreement between test methods. The methods are described solely for reporting
      changes in units of bronchial responsiveness but are applicable to other log
      normally distributed measurements.

PMID- 7722544
TI  - Prevalence of asthma in elderly Finns.
AB  - There is uncertainty about the prevalence of asthma even in countries in which
      extensive epidemiological surveys have been carried out and attention has been
      drawn to a probable increase in prevalence. A cross-sectional epidemiological
      survey of asthma in the population aged 64 years or over was carried out in the
      rural district of Lieto, Finland. All 1196 participants (488 men and 708 women,
      93% of those eligible) were examined and individually assessed using a set of
      criteria for asthma. The prevalence of current asthma was 2.9% in the men and
      3.8% in the women and it accounted for about 40% of the cumulative (life-time)
      prevalence of self-reported asthma. Current asthma was uncommon in men aged 75
      years or over and no cases were found in men who smoked. Current asthma in women
      was associated with low social status, smoking and dusty working conditions in
      the past. The difference in prevalence between the men and women was greatest
      among the smokers, which may be due to a previous high mortality among elderly
      asthmatic men who had been smoking, or a lack of the typical characteristics of
      asthma in men with long histories of smoking. The prevalence of asthma was
      similar to that obtained earlier in Finland and elsewhere.

PMID- 7722545
TI  - Comparison of chemotherapy and bone marrow transplants using two independent
      clinical databases.
AB  - Comparing the outcome of chemotherapy and bone marrow transplants in the absence
      of a randomized trial is difficult but necessary for diseases where small numbers
      of patients make such trials difficult if not impossible. To address this issue
      for adults with acute lymphoblastic leukemia in first remission, we created an
      empirical database using two separate datasets, one from the International Bone
      Marrow Transplant Registry and the other from two multicenter chemotherapy
      studies. Prior to combining the datasets, a study protocol was developed to
      define inclusion criteria, outcomes to be compared and statistical methods. The
      main problems of a non-randomized comparison are biases potentially introduced by
      differences in baseline composition of the two cohorts and differences in time-to
      treatment. The source of the latter bias is different distributions of waiting
      times between achieving complete remission and receiving post-remission therapy.
      Several techniques to control these biases were evaluated; each gave
      qualitatively similar results. These methods can easily be applied to other
      clinical situations where randomized trials are not available.

PMID- 7722546
TI  - Patterns of comorbidity in elderly patients with multiple sclerosis.
AB  - This study explored the prevalence of comorbid conditions in hospitalized
      patients with multiple sclerosis (MS) who were 65 years of age or older. Using
      1989 data from the Quality of Care Medicare Provider Analysis and Review (MEDPAR)
      file, hospitalized MS patients were compared with respect to discharge diagnoses
      to an age- and sex-matched group of hospitalized patients without MS. As
      expected, the following discharge diagnoses were more common (P < 0.05) for MS
      patients: urinary tract infection, pneumonia, septicemia and cellulitus. In
      contrast, MS patients were less likely (P < 0.05) to have discharge diagnoses of
      acute myocardial infarction, heart failure, hypertension, angina pectoris,
      cerebrovascular disease, diabetes mellitus and chronic obstructive pulmonary
      disease. Possible explanations include under-reporting of certain comorbid
      conditions on discharge records of MS patients, a protective effect of MS or its
      treatment, reduced prevalence of risk factors, disproportionate mortality in
      younger MS patients with comorbidity and the benefits of medical surveillance.

PMID- 7722547
TI  - Impact of cardiovascular disease on health care utilization in a defined diabetic
      population.
AB  - We studied the impact on annual medical care utilization and costs in 1988 of
      cardiovascular disease (CVD) in a population-based sample of 435 diabetic (DM)
      and 435 matched non-DM members of a Health Maintenance Organization. 58% of DM
      had at least one diagnosed CVD, compared to 26% of non-DM. 22.7% of outpatient
      visits, 38.7% of hospital days, and 30% of pharmacy expenditures by those with DM
      were primarily attributable to CVD. Up to 27% of all CABG recipients in the
      population had diabetes. In total, CVD directly accounted for at least 24% of
      total medical care costs among DM, compared to 12% of costs for non-DM. The HMO
      spent 4.5 times per person more on CVD care in DM than in non-DM members.
      Treatment with insulin was associated with increased peripheral vascular disease.
      After adjusting for age, CVD was more prevalent and generated longer hospital
      stays in DMs with nephropathy. The etiologic association between CVD and DM is
      well documented but CVD's clinical and economic importance in DM seems
      underappreciated.

PMID- 7722548
TI  - Differences between smokers, ex-smokers, passive smokers and non-smokers.
AB  - The extent to which current, ex- and passive smoking are associated with other
      risk factors, and the potential for confounding arising from these associations,
      was studied using a representative sample of 9003 British adults. The
      distribution of 33 lifestyle factors generally considered associated with adverse
      health were compared in current smokers, ex-smokers, never smokers living with a
      smoker ("passive smokers") and other never smokers. Of the 33 risk factors 27
      showed a significantly higher prevalence in heavy smokers than in never smokers
      and only two showed a lower prevalence. For many risk factors, prevalence
      increased with amount smoked, decreased with time of smoking cessation and was
      increased in passive smokers. The possible magnitude of bias from confounding by
      the risk factors is estimated. It is concluded that confounding by multiple risk
      factors may be an important issue in smoking studies where weak associations are
      observed. This applies particularly to studies investigating the possible
      association of passive smoking with various health effects.

PMID- 7722549
TI  - Descriptive study of lipid-modulating drug use in a French professional
      population.
AB  - The objectives of this cross-sectional study presented as the first stage of a
      cohort follow-up pharmacoepidemiological study of lipid modulators, are to
      determine the extent and pattern of use of antihyperlipidemics and concomitant
      drugs and to compare antihyperlipidemic subgroups. The study population are the
      17,244 respondents to the 1991 questionnaire in which questions on drug
      utilization were asked for the first time. It comprises 40.5% of the men and 32%
      of the women of the population originally targeted in 1989, i.e. the entire
      workforce of a national company within an age range of 35-45 years for men and 35
      50 years for women. Self-reported health events and drug use over the previous
      year were measured. Overall 1 year prevalence of use of lipid lowering drugs was
      7.7% (9.5% in men and 2.7% in women). Most antihyperlipidemics were fibrates (n =
      878), with fenofibrate ranking above ciprofibrate, as opposed to HMG-CoA
      reductase inhibitors (n = 436), principally simvastatin. Only 60% of
      antihyperlipidemic drug users were following a prescribed lipid-lowering diet;
      over half were taking other drugs concomitantly, most often b-blockers. The
      simvastatin group differs from the fibrate group by an excess of prevalent
      thyroid disease. The link between simvastatin and thyroid disease may be
      indication-related. In conclusion, the relevant features of this study are the
      extensive use of antihyperlipidemics, frequently, without concomitant diet, and
      the marked preference for antihyperlipidemics for which long term safety is
      unknown. Extent of use and choices of antihyperlipidemics are corroborated by
      estimations in the general middle-aged population.

PMID- 7722550
TI  - Are public library books contaminated by bacteria?
AB  - The microbial flora on the surfaces of 15 books obtained from a public library
      and from 15 books obtained from a family household were studied. Staphylococcus
      epidermidis was recovered from 4 of the library books and 3 of the family
      household books. The number of organisms per page was between one to four. This
      data illustrates the safety of using library books, as they do not serve as a
      potential source of transmission of virulent bacteria.

PMID- 7722551
TI  - Ranitidine-associated autoimmune hemolytic anemia in a health maintenance
      organization population.
AB  - Reversible hematologic abnormalities including hemolytic anemia [1] with a
      positive direct Coombs' test have been associated with ranitidine. In addition to
      the case report cited above, the U.S. Food and Drug Administration had received
      five other cases of hemolysis associated with recent intake of ranitidine as of
      February 1991. To investigate the possible association of ranitidine with
      autoimmune hemolytic anemia, a study was conducted to determine how often
      diagnoses of hemolytic anemia or abnormal Coombs' test results followed
      dispensing of ranitidine using the automated medical and pharmacy records of a
      large health maintenance organization. No occurrences of hemolytic anemia were
      identified among 12,054 individuals following 38,686 prescriptions for this
      medication. The 95% upper confidence bound was 3.1 cases/10,000 exposed persons.
      One abnormal direct Coombs' test with mild anemia was discovered during routine
      prenatal testing of an asymptomatic patient who was dispensed ranitidine two and
      a half months previously. Hemolysis, however, was not demonstrated and an
      association with prior ranitidine use could not be confirmed. Additional analyses
      indicate that in only 30% of ranitidine courses was a blood count obtained. In
      those courses with hematocrits below 40%, less than 1% had a Coombs' test
      performed. Chart review suggests that the majority of individuals with severe
      anemia have alternative explanations other than autoimmune hemolysis for their
      anemia. This analysis indicates that ranitidine is unlikely to be a common cause
      of clinically recognized autoimmune hemolytic anemia and demonstrates the utility
      of large automated medical and pharmacy data bases to conduct post-marketing
      studies of spontaneously reported drug effects.

PMID- 7722552
TI  - Is race related to glycemic control? An assessment of glycosylated hemoglobin in
      two South Carolina communities.
AB  - To consider the relationship between race and long-term glycemic control, as
      measured by glycosylated hemoglobin (GHb), we analyzed data from a community
      based sample of 3175 adults in the South Carolina Cardiovascular Disease
      Prevention Project. A clinically meaningful difference for mean GHb levels (10.5
      vs 8.4%, P < 0.001) was present between black people and white people reporting
      diabetes. Similarly, a significant association between race and GHb was present
      among people reporting "borderline diabetes" or no diabetes. Logistic regression
      confirmed this finding in all three diabetic categories, however, controlling for
      insulin use in the diabetic group reduced (P < 0.001) the association between GHb
      and race. These findings confirm that further improvements in glycemic control
      are necessary, especially for black patients and that black people not reporting
      diabetes have higher GHb levels compared to white people, possibly due to
      undiagnosed diabetes.

PMID- 7722553
TI  - Replicating the chronic disease score (CDS) from automated pharmacy data.
AB  - Michael Von Korff and colleagues at the Center for Health Studies, Group Health
      Cooperative (GHC) of Puget Sound created a measure of chronic disease status
      (CDS) using automated outpatient pharmacy data. They reported the measure
      appeared to provide a stable and valid measure of health status. The availability
      of such a measure could become a new tool for a variety of applications,
      including screening, resource allocation, and quality assurance. The measure was
      replicated for its reliability and construct and predictive validity in the KPNW
      membership using automated pharmacy data. Reliability and validity were tested
      using correlation and regression techniques. The CDS showed test-retest
      reliability over time. It showed construct validity with the RAND-36 instrument
      and the BSI-8 depression screener. It showed predictive validity with health care
      visits and hospitalizations. The results were similar to those at GHC. The
      findings indicated that the CDS can serve, with certain precautions, as a readily
      accessible low cost measure of health status.

PMID- 7722554
TI  - Statistics and antibiotics.

PMID- 7722555
TI  - A case-control study of drugs and other determinants as potential causes of
      Guillain-Barre syndrome.
AB  - The Guillain-Barre syndrome is an inflammatory demyelinating polyneuropathy with
      an acute or subacute onset. The current case-control study was performed to
      investigate the possible role of drugs and other determinants in the causation of
      the Guillain-Barre syndrome. Patients were included as cases if they fulfilled
      the criteria for acute Guillain-Barre syndrome and were unable to walk 10 m
      independently and had been admitted to the hospital within 2 weeks of onset of
      the neuropathy. For every case, two controls without the disease were obtained
      from the general practitioner (GP) of the patient with Guillain-Barre syndrome.
      Controls had the same type of health care insurance, were of the same gender and
      age (within 5 years), and resident in the same area. By telephone, the GPs of the
      patients with Guillain-Barre syndrome were interviewed. There were 71 female and
      75 male cases and 142 female and 149 male controls. Significantly more cases than
      controls had been prescribed drugs in the 3 months prior to the index date and
      also diagnoses or symptoms in cases were more common. Case patients used
      significantly more frequently antipropulsives (loperamide), penicillins
      (amoxicillin with or without clavulanic acid) and vaccines. Female controls used
      significantly more often oral contraceptives. More cases than controls suffered
      from infections of the respiratory, gastrointestinal or urinary tract prior to
      the onset of neurological symptoms. In a logistic regression analysis, symptoms
      concerning the gastrointestinal and respiratory system were strongly associated
      with the Guillain-Barre syndrome. The use of oral contraceptives was
      significantly lower in female cases which could be compatible with the hypothesis
      that these drugs are protective.

PMID- 7722556
TI  - Breast silicone implants and risk of systemic lupus erythematosus.
AB  - The uncertain safety of breast implants has been a major controversy of late,
      both in the lay press and in the scientific literature. A case-control study had
      been performed in the Philadelphia metropolitan area during 1985-1987 to
      investigate potential risk factors for systemic lupus erythematosus (SLE). A
      total of 219 eligible cases who met the American Rheumatism Association criteria
      for SLE were identified from the medical practices of cooperating rheumatologists
      in the area; 195 (89%) of these were enrolled in the study. Friends of the cases,
      matched to the cases on sex and age (+/- 5 years) served as controls. For the
      current investigation, conducted during June 1992 through September 1992, we
      attempted to re-contact each of these individuals. Using a short telephone
      interview, we asked each subject to provide information on any surgery that they
      may have had prior to the index date, i.e. the year of diagnosis of SLE in the
      cases and the same year for the age-matched friend controls. Specific questions
      were asked about plastic surgery in general and breast implants in particular.
      148 (75.9%) of the 195 SLE cases being sought and 111 (77.6%) of the 143 controls
      being sought agreed to be re-interviewed for this study. Only 1 (0.8%) out of 133
      female SLE cases reported having had a breast implant, 8 years prior to the
      diagnosis of SLE. This compared to 0 out of the 100 female friend controls
      (Fisher exact one-tailed p-value = 0.57).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722557
TI  - Preferences of pregnant women for amniocentesis or chorionic villus sampling for
      prenatal testing: comparison of patients' choices and those of a decision
      analytic model.
AB  - Decision analytic models have suggested that the choice of amniocentesis or
      chorionic villus sampling for prenatal genetic testing is a utility-driven
      decision. We compared preferences for prenatal testing among 156 pregnant women
      who had chosen either amniocentesis (n = 82) or chorionic villus sampling (n =
      74) for the indication of maternal age. We also compared their choices with those
      of a decision-analytic model based on their preferences, and age-specific rates
      of spontaneous abortion and chromosomal abnormalities. Preferences were assessed
      using written scenarios describing potential outcomes of prenatal testing, and
      were recorded on linear rating scales. The differences in preference ratings for
      first- vs second-trimester prenatal diagnosis of a normal child (4.2 vs -1.6, p =
      0.0004), and for first- vs second-trimester abortion of an abnormal fetus (4.4 vs
      -1.6, p = 0.01), were significantly greater among women choosing chorionic villus
      sampling than among women choosing amniocentesis. There were no significant
      differences between chorionic villus sampling and amniocentesis patients in their
      preference ratings for test-related miscarriage, disconfirmed results at
      pregnancy termination, or maternal morbidity from therapeutic abortion. After
      adjusting for demographic and obstetric factors, the difference in preferences
      for early vs late prenatal diagnosis was an independent predictor of the choice
      of chorionic villus sampling in a multivariate model. Among women whose decision
      analyses selected amniocentesis, 56.8% had chosen amniocentesis, and among women
      whose analyses selected chorionic villus sampling, 63.2% had chosen chorionic
      villus sampling (p = 0.05). We conclude that the preferences of pregnant women
      for the outcomes of prenatal testing were associated with their choice of
      amniocentesis or chorionic villus sampling. In addition, the choice of prenatal
      test made by the majority of women was concordant with that of a decision
      analytic model that incorporated their preferences. Nevertheless, because many
      women made choices that were discordant with their decision-analytic results,
      further research into the bases for their choices is warranted.

PMID- 7722558
TI  - Lack of association between patients' measured burden of disease and risk for
      hospital readmission.
AB  - Identifying patients at increased risk for hospital readmission is important for
      clinicians, health policy-makers, hospital administrators, and researchers. We
      used a retrospective case-control design to compare the clinimetric properties of
      five validated indices that measure a patient's disease burden. The study was
      conducted on a random sample of patients discharged from the general medicine
      service at the Durham Department of Veterans Affairs Medical Center. Trained
      observers (two research assistants, one nurse, and two physicians) blinded to
      readmission status abstracted the required data elements from the medical record
      for three indices (Charlson, Kaplan-Feinstein, Index of Coexistent Disease). The
      hospital's computer provided data elements for two indices (Smith, adapted
      Charlson). Indices varied in the time required to complete, the ability to
      capture individual heterogeneity, and inter-observer variability. However, none
      of the indices discriminated among patients who did and those who did not have 6
      month hospital readmissions. Factors other than summary scores derived from these
      indices should be used to identify patients at high risk for readmission.

PMID- 7722559
TI  - A marked decline in the prevalence and incidence of intermittent claudication in
      Icelandic men 1968-1986: a strong relationship to smoking and serum cholesterol-
      the Reykjavik Study.
AB  - The epidemiology of peripheral vascular disease has been studied much less
      extensively than the epidemiology of coronary heart disease (CHD). The
      prospective Reykjavik Study gave an opportunity to monitor secular trends from
      1968 to 1986 of clinical intermittent claudication (IC) amongst Icelandic males,
      aged 34-80 and to assess the importance of possible risk factors. Both prevalence
      and incidence of IC decreased sharply after 1970 in all age groups, and this
      decline occurred a few years earlier than the decline of CHD in Iceland. The only
      significant risk factors for intermittent claudication, in addition to age, were
      smoking which increased the risk of IC 8- to 10-fold and serum cholesterol level.
      Approximately one-half of the striking decline in the incidence of IC can be
      explained by decreased smoking and cholesterol levels amongst Icelandic men. A
      follow-up study verified that IC patients stood twice the risk of cardiovascular
      and total mortality as non-IC patients, indicating that IC is a high risk group
      which should receive all possible preventive measures.

PMID- 7722560
TI  - Validation of a combined comorbidity index.
AB  - The basic objective of this paper is to evaluate an age-comorbidity index in a
      cohort of patients who were originally enrolled in a prospective study to
      identify risk factors for peri-operative complications. Two-hundred and twenty
      six patients were enrolled in the study. The participants were patients with
      hypertension or diabetes who underwent elective surgery between 1982 and 1985 and
      who survived to discharge. Two-hundred and eighteen patients survived until
      discharge. These patients were followed for at least five years post-operatively.
      The estimated relative risk of death for each comorbidity rank was 1.4 and for
      each decade of age was 1.4. When age and comorbidity were modelled as a combined
      age-comorbidity score, the estimated relative risk for each combined age
      comorbidity unit was 1.45. Thus, the estimated relative risk of death from an
      increase of one in the comorbidity score proved approximately equal to that from
      an additional decade of age. The combined age-comorbidity score may be useful in
      some longitudinal studies to estimate relative risk of death from prognostic
      clinical covariates.

PMID- 7722561
TI  - Factors affecting the incidence of death at home of residents of Hida district,
      Japan.
AB  - This study compared the percentage of residents who died from disease at home in
      Hida district, Japan, between the years 1979-1981 and 1989-1991, and found it
      decreased from 46.9% during the earlier period to 32.6% during the latter. It
      differed significantly by age and underlying cause of death. Residents aged 85
      and over were almost twice as likely to die at home as were all other subjects.
      Patients who died of malignant neoplasms showed the lowest proportion of death at
      home. A greater percentage of residents who lived far from hospitals or those who
      had the causal disease for a prolonged time died at home. The proportion for 1989
      1991 was lower than that for 1979-1981 after adjustment for age, gender, cause of
      death, period of illness, and availability of hospital. It was speculated that
      the increase of hospital beds affected the proportion of death at home.

PMID- 7722562
TI  - Declining trends in incidence, case-fatality and mortality of stroke in three
      geographic areas of Finland during 1983-1989. Results from the FINMONICA stroke
      register.
AB  - Stroke mortality has decreased during the last decade in many industrialized
      countries, but there has been no clear evidence for a decline in the incidence of
      stroke. The present study analyzes the trends in the incidence, mortality and
      case-fatality of stroke in Finland from 1983 to 1989. We used data from the
      FINMONICA stroke register, a community based register collecting information on
      all suspected stroke cases aged 25-74 in three geographical areas of Finland.
      Annual attack rate, incidence, mortality and case-fatality rates were calculated
      for all strokes and for different subcategories of stroke. A linear regression
      model was applied to calculate the yearly trends of these rates. In men, the
      attack rate of stroke was 336/100,000 in 1983 and 310/100,000 in 1989 (-8% during
      the observation period); incidence declined from 269/100,000 in 1983 to
      236/100,000 in 1989 (-12%); mortality declined from 82/100,000 to 64/100,000 (
      22%), and case-fatality declined from 25% to 21% (-18%). Also among women similar
      declining trends were observed (-11%, -13%, -16%, and -10% respectively), but
      they were not statistically significant. In both incidence and mortality of
      stroke, the decline was seen in all age groups. Incidence and mortality of
      cerebral infarction declined similarly to all strokes. A large fall in the
      incidence (-24% in both men and women) and mortality (-38% in men and -27% in
      women) of subarachnoid haemorrhage was also observed. An increasing trend,
      although not significant, was instead observed for cerebral haemorrhage. First
      stroke and especially first cerebral infarction contributed most to the decline
      in case-fatality. The availability of computerized brain tomography improved from
      18% in 1983 to 60% in 1989. We observed a fall in the incidence, mortality, and
      case-fatality of stroke during 1983-1989. Among the subtypes of stroke, cerebral
      infarction contributed most to the decline, but the data suggested also a
      declining trend in the incidence and mortality of subarachnoid haemorrhage,
      observed now for the first time in Finland since the 1960s. The fall in the
      incidence of stroke was not as steep during the 1980s as it was during the 1970s;
      Finland is anyhow the only European country which has reported a decreasing trend
      in stroke incidence during the 1980s. We need now to investigate how much the
      decline in the classical risk factors for stroke observed in Finland during the
      last two decades predicts the observed trends.

PMID- 7722563
TI  - The accuracy of self-report of herpes zoster.
AB  - The accuracy of self-report of herpes zoster was investigated in the Duke
      Established Populations for Epidemiological Studies of the Elderly, a
      longitudinal study of 4162 community-dwelling elderly persons residing in North
      Carolina, 1986-1993. The authors compared self-reports of zoster with physician
      diagnosis of zoster and with a zoster verification questionnaire (ZVQ). Compared
      to physician diagnosis, 3.2% (95% confidence interval 0-61%) of self-reports of
      zoster (n = 31) were false-positive and no denials of zoster (n = 63) were false
      negative. The agreement of self-reports to physician diagnosis was 98.9%, the
      sensitivity and negative predictive value were 100%, the specificity was 98.4%
      and the positive predictive value was 96.7%. The ZVQ comparisons were similarly
      high. These data suggest that the frequency of false-positive and false-negative
      reports of zoster is low in this elderly population. Zoster self-reports appear
      to be accurate and suitable for epidemiological investigations.

PMID- 7722564
TI  - Planning for precision in survival studies.
AB  - If the purpose of a clinical study is not only to test the null hypothesis but
      also to estimate the magnitude of the treatment effect, the study design should
      ensure not only that the study will have adequate power but also that it will
      enable the researcher to report the relevant parameters with an appropriate level
      of precision. This paper discusses the factors that control precision in survival
      studies and shows how a computer program may be used to address these issues. The
      program allows the user to systematically modify assumptions about the population
      (e.g. the magnitude of the hazard ratio or the attrition rate) and elements of
      the study design (e.g. sample size and trial duration), quickly identify the
      impact of these factors on the study's precision, and modify the study design
      accordingly. The program may also be used to compute power for a planned study,
      and confidence intervals for a completed study.

PMID- 7722565
TI  - Quality of life after myocardial infarction.
AB  - The objective of this work was to develop and test a questionnaire to measure
      health-related quality of life for patients after myocardial infarction (MI). In
      a cross-sectional survey, 63 patients identified the most frequent and important
      problems following acute myocardial infarction. The Quality of Life after
      Myocardial Infarction (QLMI) instrument was developed on the basis of these most
      frequent and important problems. The QLMI was administered, along with
      instruments measuring health utilities, social function, and emotional function,
      in a randomized trial of rehabilitation versus conventional care. The most
      frequent and important problems fell into areas of symptoms, restriction,
      confidence, self-esteem, and emotions, each of which is represented in the 26
      item QLMI. Effect sizes of the overall QLMI in differentiating between
      rehabilitation and control groups (0.35), and in detecting improvement over 12
      months (1.22) were comparable or larger than any other instrument. The Pearson's
      correlation coefficient between QLMI administered at 8 and 12 months following
      AMI varied between 0.75 and 0.87 for the five domains and the overall score. We
      found substantial correlations of the QLMI with other measures with moderate
      concordance with predictions about how the instrument should behave if it is a
      valid measure of health-related quality of life. The QLMI demonstrates a high
      degree of reliability, and is more responsive than other questionnaires.
      Relations between the QLMI and other measures provide moderate to strong evidence
      of its validity in discriminating between patients following AMI according to
      their health-related quality of life, and in measuring changes in health-related
      quality of life over time.

PMID- 7722566
TI  - Epidemiology of hemophilia and of HIV infection in Italy. GICC. Gruppo Italiano
      Coagulopatie Congenite.
AB  - To evaluate the incidence and prevalence of hemophilia in Italy and the impact of
      HIV infection on the Italian hemophiliac population, data from a computerized
      national registry of patients from 95% of the hemophilia care centers in Italy
      were analyzed. A total of 4643 patients were included in the registry. The
      prevalence of hemophilia A was 8.2 per 100,000 males, with no significant
      regional differences; for hemophilia B the corresponding figure was 1.5 per
      100,000. Temporal trends in hemophilia incidence suggest that the diagnosis of
      mild and moderate hemophilia has improved. The overall HIV prevalence was 26% and
      was significantly (p < 0.001) higher in patients with hemophilia B (47.1%)
      compared to those with hemophilia A (26.8%) or other diseases (16.5%). The
      highest rate of HIV seropositivity was among patients 20-29 years of age. The
      annual amount of clotting factor concentrates received was significantly (p <
      0.001) higher in HIV seropositive patients than in those who were seronegative.
      Antibody testing was never performed on 10.1% of severely affected patients. The
      number of patients in the Italian registry was similar to the number that would
      have been expected based on prevalence estimates from other countries. In
      comparison with other countries, the prevalence of HIV infection recorded in
      Italy was lower in persons with hemophilia A, but higher in those with hemophilia
      B. Our study demonstrates the usefulness of a registry in delineating the
      epidemiology of hemophilia and in studying risk factors for HIV infection. It
      also underlines the need for continuing surveillance of this population.

PMID- 7722567
TI  - Cost effectiveness of accelerated rehabilitation after proximal femoral fracture.
AB  - A randomised controlled trial comparing an accelerated rehabilitation program
      after proximal femoral fracture with conventional care and rehabilitation was
      conducted with 252 elderly patients treated at an Australian general hospital in
      1989/1990. This paper presents a cost-effectiveness analysis of the accelerated
      rehabilitation program. The measure of cost was all direct costs of treatment and
      subsequent care (medical and non-medical) incurred during the 4 months after
      fracture. Effectiveness was defined as whether the patient returned to semi
      independent living; or if moderately or severely disabled prior to the fracture
      to the premorbid level of physical independence. The cost for treatment up to 4
      months after fracture was estimated at A$ 10,600 per accelerated rehabilitation
      patient and A$ 12,800 per conventional care patient (1990 Australian dollars,
      A$). Thus, accelerated rehabilitation releases resources equivalent to
      approximately 17% of costs for treatment per patient. When cost effectiveness is
      considered, the potential cost savings rise to 38% per recovered patient.

PMID- 7722568
TI  - Modelling observer agreement--an alternative to kappa.
AB  - The measurement of agreement among several observers of the same phenomenon has
      traditionally been analyzed with a kappa coefficient. Recently, methodology for
      the modelling of such interobserver agreement has been developed. The details and
      advantages of this methodology are demonstrated by way of the analysis of three
      examples. Directions for the fitting of these models using the computer program
      SPSS-X are included in the Appendix.

PMID- 7722569
TI  - The prevention of cancer--a sobering perspective.

PMID- 7722570
TI  - The quandary of cancer prevention.
AB  - The incidence and mortality due to the major cancers such as lung, breast, colon
      rectum, prostate, and ovary have changed very little over the past 20-30 years,
      in spite of the introduction of important new treatments and apparent
      prolongation of survival of patients with these cancers. The new strategies focus
      on earlier detection and primary prevention of cancer. Three approaches for
      prevention are receiving increasing prominence as an approach to reducing the
      incidence of cancer: (1) control of common source environmental carcinogens, (2)
      modification of personal health behavior believed to increase or decrease the
      risk of cancer, and (3) identification of specific genotypes that increase the
      risk of cancer. All of these approaches offer some hope of reducing cancer
      incidence and morbidity. All will be costly and, therefore, require careful
      evaluation. It is likely that the changes in personal health behaviors will have
      the greatest overall impact on cancer incidence. Identification of specific
      genotypes will be of importance for high risk families. At present, it is
      unlikely that control of environmental common sources will substantially reduce
      cancer incidence without better measures of exposure and risk of disease.

PMID- 7722571
TI  - New models for predicting cardiovascular events.
AB  - Data from the Framingham Heart Study are used to derive equations for long-term
      predicted probabilities for death and a variety of cardiovascular endpoints. An
      accelerated failure method is employed, first the standard Weibull model and then
      a useful extension. The extension relaxes the assumption of proportional hazards
      implied by the standard Weibull model. Models differ markedly in form for the
      various endpoints, but in every case the varying scale model provided a
      significantly better fit. The resulting differences in predicted probability may
      be important in planning community health projects or clinical trials and in
      carrying out cost-benefit analyses.

PMID- 7722572
TI  - The evolution of clinical practice and time trends in drug effects.
AB  - Evidence from contemporary studies suggests that the quantification of adverse
      drug effects through state-of-the-art non-experimental methods may be confounded
      by some aspects of clinical practice. Support for this hypothesis is manifest in
      the finding that drug effects sometimes show within-study time trends when
      clinical practice with regard to drug use is evolving. Three studies which show
      simultaneous trends in prescription frequency and drug effects are discussed as
      examples. These include a study of benzodiazepines in the etiology of hip
      fracture, postmenopausal estrogens as a preventive for major coronary disease and
      human insulin as a risk factor for severe hypoglycemia. For instance, during a
      period when clinical perceptions regarding the safety of benzodiazepine use in
      the elderly underwent gradual change, the relative risk for hip fracture among
      long half-life benzodiazepine users declined progressively from 2.0 (95% CI, 1.6
      2.5) in 1977-79 to 1.3 (95% CI, 0.9-1.8) in 1984-85. The implications of these
      observations are set against the scientific objectives which guide etiologic
      research.

PMID- 7722573
TI  - Prevalence of coronary heart disease indicated by electrocardiogram abnormalities
      and risk factors in developing countries.
AB  - A cross-sectional population survey was carried out in 15 population groups
      (ethnicity includes Melanesian, Polynesian, Micronesian, Asian Indian and
      Chinese) in 9 developing countries: Fiji, Nauru, Kiribati, Cook Island, Niue,
      Western Samoa, New Caledonia, Mauritius and China (Beijing) in 1978-1987. The
      total sample included 4594 men and 4988 women aged 35-59 years. The aim of study
      is to report the prevalence of coronary heart disease (CHD) as indicated by ECG
      Minnesota coding, and risk factor levels and to describe the individual and
      ecological relationship between CHD prevalence and CHD risk factors among
      different ethnic groups in developing countries. Mauritians had the highest
      prevalence of CHD of these countries. Total serum cholesterol concentration and
      the prevalence of CHD were higher in Mauritius Chinese than in Beijing Chinese.
      Mean total cholesterol was lower than or equal to 5.2 mmol/l (200 mg/dl) in all
      population groups, except in Mauritians. Hypertensive subjects in most
      populations had a low cholesterol concentration. The prevalence of hypertension
      varied from 7 to 35% and mean body mass index (BMI) from 22.9 to 37.0 kg/m2.
      Smoking was more common in men (36-82%) than women (0.8-65%). Multiple logistic
      regression analysis using individuals as a unit of analysis showed that
      cholesterol and systolic blood pressure were significant independent predictors
      of CHD prevalence. When fasting or 2 hr post-load blood glucose was included in
      the model total cholesterol was no longer significant in men but remained
      significant in women. Ecological analysis using populations as units of analysis
      showed that the combination of several CHD risk factors could explain about 90%
      of the interpopulations variance of the CHD prevalence in women. The best models
      were those where 2 hr post-load glucose was included. Our study has demonstrated
      that the total cholesterol concentration of the population was consistent with
      the prevalence of CHD in the population. A considerable proportion of the
      variation in CHD prevalence across populations in developing countries can be
      explained by well-known risk factors. These data support the concept that
      retaining traditional balanced dietary habits and limiting salt intake together
      with avoiding smoking use are important activities for the prevention of
      cardiovascular disease (CVD) in developing countries.

PMID- 7722574
TI  - Impact of regulation on benzodiazepine prescribing to a low income elderly
      population, New York State.
AB  - On 1 January 1989, in an effort to reduce diversion of benzodiazepines for
      illicit use and reduce inappropriate prescribing, a regulation was implemented
      requiring the reporting of all benzodiazepine prescriptions to the New York State
      Department of Health. To assess the impact of the regulation on prescribing
      practices to the elderly, we followed the number of benzodiazepines and other
      central nervous system medications prescribed to a cohort of participants in an
      elderly pharmaceutical insurance program. Benzodiazepines were prescribed for
      4652 (22%) of the 20,944 patients studied. By the last quarter of 1989,
      benzodiazepines were prescribed for 3120 (15%) patients, a decrease of 33%. The
      number of prescriptions of benzodiazepines decreased by 5010 (45%), from 11,123
      to 6113. Decreases in the number of prescriptions were similar across
      benzodiazepine brands (range 40-56%). Statistically significant (p < 0.05)
      decreases were seen in all sex, age, race and marital status groups. Increases in
      number (and percent increases) of prescriptions for miscellaneous anxiolytics
      (i.e. hydroxyzine (399, 69%), meprobamate (299, 149%), buspirone (263, 111%),
      chloral hydrate (138, 265%), antidepressants (658, 19%), barbiturates (150, 29%),
      and tranquilizers (198, 19%), some of which may be more toxic or less effective,
      were noted. New York State's reporting regulation was effective in reducing both
      the number of patients being prescribed benzodiazepines and the number of
      prescriptions given to those who remain on benzodiazepines in the elderly
      population studies.

PMID- 7722575
TI  - Chance-corrected measures of the validity of a binary diagnostic test.
AB  - Chance-corrected measures of the validity of diagnostic tests can be a valuable
      supplement to traditional measures which do not take chance-agreement between
      diagnostic test and true disease status into account. Recently, several authors
      have propagated chance-corrected measures of sensitivity and specificity, the
      most commonly employed indices of validity of binary diagnostic tests. A major
      limitation of these measures is their dependence on disease prevalence. In this
      paper, we propose simple alternative chance-corrected measures of sensitivity and
      specificity which do not share this limitation. The chance-corrected measure of
      sensitivity can be expressed as 1--negative likelihood ratio, and the chance
      corrected measure of specificity can be expressed as 1--inverse of the positive
      likelihood ratio. The properties of the proposed measures are described and
      graphically illustrated, and formulas are given for point and interval estimation
      of the measures.

PMID- 7722576
TI  - Clinical scores for acute asthma in pre-school children. A review of the
      literature.
AB  - The objective of this paper was to evaluate the applicability in research and
      clinical practice of clinical scores for acute asthma in pre-school children. All
      instruments were reviewed according to a standardized set of criteria: purpose of
      the score, suitability for use in children, inter-observer agreement, validity
      and responsiveness. A Medline literature research resulted in 16 different
      clinical asthma scores, which have been developed to assess the severity of acute
      asthma, to predict the outcome of an attack, or to evaluate the response to
      treatment. Most asthma scores could be easily obtained in children. Three scores
      have been modified to facilitate application in a younger age-category. Inter
      observer agreement has received little attention, although all scores contained
      items that require subjective judgement. The predictive validity was insufficient
      to justify the application of clinical scores as a decision rule for the
      admission or discharge of children with acute asthma. Asthma scores seem to be
      useful for assessing the severity of an attack and evaluating the response to
      therapy, but as yet there is insufficient information on the performance of the
      scores to justify a preference. Wheezing and retractions appear to be important
      items of any useful score for acute asthma.

PMID- 7722577
TI  - The difficult doctor-patient relationship: somatization, personality and
      psychopathology.
AB  - The difficult doctor-patient relationship and "difficult patients" have been the
      subject of considerable anecdotal study. Reliable methods for identification of
      difficult patients have not been available for the empirical study of their
      prevalence and characteristics. We developed the Difficult Doctor-Patient
      Relationship Questionnaire (DDPRQ), composed of 30 Likert items, completed by
      physicians after encounters with patients. Adult patients and their providers in
      an academic, municipal hospital clinic participated in the instrument development
      (n = 92), reliability (n = 224), and assessment of patient characteristics phases
      (n = 113) of the study. The DDPRQ was shown to be a reliable, practical
      instrument. Factor analysis revealed 5 dimensions with face validity. The DDPRQ
      classified 10.3-20.6% of patient encounters as "difficult" depending on the
      sample. Demographic characteristics, provider characteristics and most medical
      diagnoses were not associated with DDPRQ score. In contrast, difficult patients
      were characterized by psychosomatic symptoms, at least mild personality disorder,
      and Axis I (major) psychopathology, and most had more than one of these
      characteristics. The need to identify and understand these components of
      difficult patient behavior and to include the doctor-patient relationship in
      strategies for managing the difficult patient is discussed.

PMID- 7722578
TI  - Diagnosis of acute myocardial infarction by MONICA and FINMONICA diagnostic
      criteria in comparison with hospital discharge diagnosis.
AB  - WHO MONICA Project has suggested diagnostic criteria for acute myocardial
      infarction (AMI) for monitoring the trends of coronary heart disease (CHD). The
      aim of our study was to compare the diagnosis of AMI by the MONICA diagnostic
      criteria and by the modified criteria developed within the FINMONICA study with
      hospital discharge (clinical) diagnosis. In a series of 1565 suspected acute CHD
      events treated at Kuopio University Hospital in 1987-1990, a diagnosis of
      definite AMI was made clinically in 566 events and by the MONICA (and FINMONICA)
      criteria in 551 events. The comparability between clinical and MONICA (and
      FINMONICA) classifications was good (kappa 0.81, Ppos 0.88, Pneg 0.93). A
      diagnosis of definite or possible AMI was made clinically in 734 events, in 1249
      events by the MONICA criteria (kappa 0.25, Ppos 0.69, Pneg 0.47) and in 934
      events by the FINMONICA criteria (kappa 0.60, Ppos 0.81, Pneg 0.77). Of the 383
      events classified as possible AMI by the FINMONICA criteria the clinical
      diagnosis was "prolonged angina pectoris attack" or "unstable angina" in 39%. The
      FINMONICA diagnostic criteria for AMI are closer to clinical diagnostic
      classification and offer a possibility for a more detailed classification of
      acute CHD events than the original MONICA criteria.

PMID- 7722580
TI  - Evaluation of the MOS SF-36 physical functioning scale (PF-10): I.
      Unidimensionality and reproducibility of the Rasch item scale.
AB  - Indexes developed to measure physical functioning as an essential component of
      general health status are often based on sets of hierarchically-structured items
      intended to represent a broad underlying concept. Rasch Item Response Theory
      (IRT) provides a methodology to examine the hierarchical structure,
      unidimensionality, and reproducibility of item positions (calibrations) along a
      scale. Data gathered on the 10-item Physical Functioning Scale (PF-10) from a
      large sample of Medical Outcomes Study patients (N = 3445) were used to examine
      the hierarchical order, unidimensionality, and reproducibility of item
      calibrations. Rasch-IRT analyses generated an empirical item hierarchy, confirmed
      the unidimensionality of the PF-10 for most patients, and established the
      reproducibility of item calibrations across patient populations and repeated
      tests. These findings support the content validity of the PF-10 as a measure of
      physical functioning and suggest that valid Rasch-IRT summary scores could be
      generated as an alternative to the current Likert summative scores.
      Unidimensionality and reproducibility of the item scale are essential
      prerequisites for the development of Rasch-based person measures of physical
      functioning that can be used across populations and over repeated tests.

PMID- 7722579
TI  - Who wants to eliminate heart disease?
AB  - Twenty-seven physicians and nine pharmacists at one University teaching hospital
      identified their preferred way of dying after attaining average life expectancy.
      Respondents' ranking of modes of dying showed high agreement (for physicians, W =
      0.65, p < 10(-16)). Disease category, rapidity of death, and their interaction
      (ANOVA, all p < 0.0001) influenced choice. "Rapidly fatal cardiac death" was
      overwhelmingly preferred. Cancer and slowly fatal central nervous system
      disorders were rated last. Eliminating cardiovascular disease would necessarily
      increase the likelihood of other modes of death. If these respondents represent
      "informed consumers", then reducing cardiac death at normal life expectancy may
      be contrary to Western society's preferences.

PMID- 7722582
TI  - Begging the question.

PMID- 7722581
TI  - Are geographical differences and time trends in myocardial infarction incidence
      in Sweden real? Validity of hospital discharge diagnoses.
AB  - In Sweden, acute myocardial infarction (AMI) incidence has been found to differ
      considerably between the neighboring counties of Stockholm and Gavleborg, with an
      increase in Stockholm during the 1970s. We estimated the AMI incidence in
      Stockholm in 1973 and in both areas in 1981. To determine if there were
      differences in the validity of hospital discharge diagnoses, random samples of
      AMI patients were examined for diagnostic criteria for AMI. In both genders, AMI
      incidence was higher in Gavleborg than in Stockholm (relative risk (RR) 1.34 for
      men and 1.21 for women) and increased in Stockholm from 1973 to 1981 (RR 1.21 for
      men and 1.29 for women). The proportion of patients fulfilling the diagnostic
      criteria for AMI was similar in both areas in 1981 but 10% less in Stockholm in
      1981 than in 1973. These results suggest that differences in the validity of
      hospital discharge diagnoses cannot explain the geographical differences in AMI
      incidence, but that this may have contributed to the increasing incidence seen in
      Stockholm county.

PMID- 7722583
TI  - A comparison of two methods to ascertain dietary intake: the CARDIA Study.
AB  - Data on dietary intake were collected in the Coronary Artery Risk Development in
      Young Adults (CARDIA) Study at the baseline examination in 1985-86 and again at
      the second examination 2 years later. At baseline, a diet history questionnaire
      developed for the CARDIA study was used; at the second exam the NCI (Block) food
      frequency questionnaire was used. The purpose of the present report is to compare
      the estimated nutrient intakes obtained with the two instruments; to compare
      correlations of nutrient intakes obtained at the two exams with those observed
      for other lifestyle and physiological variables also measured 2 years apart; and
      to assess ability to test hypotheses relating 2-year changes in risk factors to
      between-exam differences in reported nutrient intakes. Mean levels of reported
      intake were generally greater for both blacks and whites on the CARDIA diet
      history than on the Block food frequency. Rank order correlations of reported
      nutrient intakes between the two questionnaires indicated greater consistency
      between instruments for whites (r's ranging between 0.35 and 0.52) than for
      blacks (r's ranging between 0.29 and 0.45). Correlations over time for nutrients
      were smaller than those observed for body size measures and lipid levels but were
      similar in magnitude to those for blood pressure, physical activity, and life
      events. At both exams, total caloric intake was positively associated with
      physical activity (range of r's for CARDIA were 0.07 for white women to 0.23 for
      black men, the range of r's for Block were 0.06 for women to 0.11 for white men).
      Using data from the two examinations, 2-year changes in total plasma cholesterol
      were significantly related to 2 year changes in Keys scores. The results of this
      comparison are useful in that they show similarities and differences between two
      instruments developed to gather dietary intake data. The study also illustrates
      the need to monitor young adults during a time when rapid changes occur in many
      lifestyle and physiologic factors.

PMID- 7722584
TI  - How should nutrient intake be measured in epidemiologic research?

PMID- 7722585
TI  - Long-term functioning and well-being outcomes associated with physical activity
      and exercise in patients with chronic conditions in the Medical Outcomes Study.
AB  - This study was carried out to determine whether levels of physical activity of
      patients with various chronic diseases are associated with subsequent functioning
      and well-being. It was an observational 2-year longitudinal design. The setting
      was offices of medical and mental health practices within health maintenance
      organizations, large multispecialty groups, and solo practices or small single
      specialty group practices in three U.S. cities. Included in the study were 1758
      adult patients with one or more of the following: diabetes, hypertension,
      congestive heart failure, recent myocardial infarction, depressive symptoms, or
      current depressive disorder. Outcome measures included physical, role, and
      functioning; energy/fatigue; pain intensity; sleep problems; depressed affect,
      anxiety, positive affect, and overall psychological distress/well-being; health
      distress; and current health perceptions. Cross-sectional (base-line), 2-year
      endpoint, and change score relationships were evaluated between baseline levels
      of physical activity and each outcome, controlling for chronic conditions,
      comorbidity, smoking, alcohol use, overweight, self-reported adherence, and other
      patient and study characteristics. Higher baseline levels of exercise were
      uniquely associated with better functioning and well-being at baseline and 2
      years later for some measures. The magnitude of the differences varied by disease
      group, but tended to be between 0.17 and 0.39 of the baseline SD. Greater levels
      of exercise are associated with feeling and functioning better for patients with
      chronic conditions over a 2-year period, suggesting that this is a fruitful area
      for further study using controlled interventions.

PMID- 7722586
TI  - Evidence of the depletion of susceptibles effect in non-experimental
      pharmacoepidemiologic research.
AB  - Past experience with a drug may modify the risk of adverse event associated with
      current use of this drug. This effect was investigated empirically with a study
      on non-steroidal anti-inflammatory drugs (NSAIDs)-gastropathy. A hospital-based
      case-control study was conducted with 244 cases of upper gastrointestinal
      bleeding (UGIB) age 68 and over and 615 matched controls. Data on all medications
      dispensed to the study patients during the 3 years preceding admission were
      obtained from the Quebec universal prescription program automated database.
      Recent use (within 30 days prior to admission) of non-aspirin NSAIDs increased
      the risk of UGIB. The estimate of relative risk (RR) was 3.4 (CI, 2.1-5.5). Use
      of NSAIDs in the previous 3 years was associated with a lower risk of UGIB; the
      estimate of RR was 0.7 (CI, 0.4-1.0). The estimate of RR for first-time users was
      22.7 (2.8-200.0) vs 3.0 (1.9-4.7) for those who had used the drugs at least once
      in the past 3 years. These results provide empirical evidence of a depletion of
      susceptibles effect whereby patients who remain on the drugs are those who can
      tolerate them while those who are susceptible select themselves out of the
      population at risk. Thus, past use should be considered as a potential risk
      modifier in non-experimental risk assessment of events associated with drug use.

PMID- 7722587
TI  - Acculturation and the initiation of breastfeeding.
AB  - Despite the fact that breastfeeding is the most appropriate form of nutrition for
      the healthy term infant, the rate of initiation in the U.S. is declining. One
      demographic factor associated with this low rate is ethnicity and so in this
      study we measured acculturation (one aspect of ethnicity) into the U.S. and its
      relationship to the successful initiation of breastfeeding in a sample of women
      recruited approximately 2 months prenatally in a U.S.-Mexico border city.
      Interviews were administered in English or Spanish by bilingual interviewers
      prenatally (n = 906), natally (n = 788), and postnatally (n = 715). Acculturation
      (measured with a 20 item instrument) was strongly related to the intent to (p <
      0.001) or the successful initiation of breastfeeding (p < 0.001). Marital status
      (p = 0.014) and education (p = 0.002) were related to breastfeeding prenatally
      and natally. Initiation of breastfeeding was highest among those women least
      acculturated (52.9%) and lowest in those most acculturated (36.1%) indicating an
      inhibiting effect of acculturation. To improve the rate of initiation of
      breastfeeding in the U.S. (a national health goal) intervention programs must
      consider cultural factors.

PMID- 7722588
TI  - Physical disability in older adults: a physiological approach. Cardiovascular
      Health Study Research Group.
AB  - Measures of physical function have been developed primarily to assess health
      status, prognosis, and service needs. They are now, increasingly, being used as
      outcome measures in studies seeking to determine the causes of disability.
      However, the extent to which these standardized measures, as they currently are
      constituted, are meaningful for the evaluation of underlying pathophysiology is
      not defined. To assess evidence for an etiologic rationale for these measures, we
      evaluated self-report of difficulty in physical function in the Cardiovascular
      Health Study, a study of 5201 men and women 65 years and older in four U.S.
      communities. We determined (by factor analysis) that self-reported difficulty
      with each of 17 tasks of daily life aggregates in four groups; i.e. difficulty in
      one task is associated with having difficulty in the other tasks in the group.
      These groups include (1) activities primarily dependent on mobility and exercise
      tolerance; (2) complex activities heavily dependent on cognition and sensory
      input; (3) selected basic self-care activities; and (4) upper extremity
      activities. Groups 2 and 3 are similar, but not identical, to Instrumental
      Activities of Daily Living (IADL) and Activities of Daily Living (ADL),
      respectively. We then tested whether these groupings were associated with
      different underlying impairments. Multiple logistic regression analyses indicate
      that there are constellations of physiologic and disease characteristics
      significantly (p < 0.01) associated with difficulty in each of these four groups
      of activities, among 15 chronic diseases and conditions ascertained. Some
      diseases are uniquely associated with difficulty in one group of tasks; some
      overlap, and are associated with 2, 3 or 4 groups of tasks. The associations
      found with difficulty in performing tasks in groups 2 and 3 were frequently
      stronger than those with the larger groups of ADL or IADL tasks, suggesting
      increased specificity of associations found with these new groupings. These
      results suggest that re-grouping of tasks of daily life may provide a more
      refined physiologically-based outcome measure for use in evaluating causes of
      disability. The ability to define risk factors for disability may be enhanced by
      choosing outcome measures with a demonstrated physiologic rationale.

PMID- 7722589
TI  - Effects of offering advance directives on quality adjusted life expectancy and
      psychological well-being among ill adults.
AB  - Two hundred and four patients from various clinical services at the San Diego
      Veterans' Administration Medical Center and the University of California, San
      Diego Medical Center were randomly assigned to either experimental (offered the
      opportunity to execute an Advance Directive regarding the level of care they
      wanted to receive if incapacitated) or control (no Advance Directive offered)
      conditions. Patients were given a baseline interview and re-interviewed at
      specific intervals (3 months, 6 months, 1 year and 2 years after baseline, and
      every 6 months thereafter). Outcome measures included the Qualitty of Well-being
      Scale, a measure of health status, and the General Well-being Index, a measure of
      psychological well-being. All differences between the health status and
      psychological well-being of experimental and control groups 3.5 years after the
      randomization were non-significant. Methodological implications of including
      mortality as part of the outcomes are discussed.

PMID- 7722590
TI  - Does a history of hypertension influence the prognosis among diabetics with acute
      chest pain?
AB  - The purpose of this study was to relate the 1-year risk of death and development
      of acute myocardial infarction among diabetics with acute chest pain to whether
      they had a history of hypertension or not. All patients with a history of
      diabetes mellitus who, during 21 months, were admitted to the Emergency Room in
      Sahlgrenska Hospital, Goteborg, due to chest pain or other symptoms suggestive of
      acute myocardial infarction, were included. Among the 427 patients with a history
      of diabetes mellitus 44% also had a history of hypertension. These hypertensives
      had a 1-year mortality rate of 22% as compared with 26% in diabetics without such
      a history (p > 0.2). The corresponding values for development of myocardial
      infarction during 1 year were 33 and 30%, respectively (p > 0.2). We did not find
      a history of hypertension to adversely affect the prognosis among diabetics with
      acute chest pain.

PMID- 7722591
TI  - Approaches to quality control with an application to a new cancer registry in a
      developing country.
AB  - Quality control should be maintained in all disease registries by appropriate
      statistical procedures to assure complete, accurate, reliable, and timely
      morbidity and mortality data. Shewhart control charts are recommended for
      evaluating item completeness. Accuracy and reliability can be evaluated with
      stringent diagnostic criteria, re-abstraction of records, and statistical
      measures such as the kappa statistic. Discrepancies between observed and expected
      data in various time periods can be used to evaluate whether data entering a
      registry meet timeliness criteria. The reporting delay distribution can be used
      to examine timeliness of reported data and to adjust incidence rates for
      potential lack of timeliness in reporting. An application of these quality
      control procedures is demonstrated using two variables selected from a hospital
      based study consisting of 119 breast cancer records collected from the Division
      of Medical Records, Dr Soetomo Hospital, Surabaya, Indonesia. The results
      indicate that the variable LASTNAME met the selected criteria for completeness
      and reliability. The variable ADDRESS met the reliability but not the
      completeness criterion. All reported cases met the timeliness criterion. The
      demonstration confirmed the need for registries to establish formal quality
      control procedures.

PMID- 7722592
TI  - Can there be a more patient-centred approach to determining clinically important
      effect sizes for randomized treatment trials?
AB  - Sample sizes for treatment trials with categorical outcomes are conventionally
      derived by balancing three elements: a difference between alternative treatments
      in the event rates for the outcomes of interest (commonly termed the clinically
      important difference), the alpha error tolerance (false positive risk) and the
      beta error tolerance (false negative risk). Clinically important differences used
      to plan trials are chosen in part based on earlier experience with similar
      interventions (i.e. biological or clinical plausibility). Methodological
      conventions and clinicians' perceptions will also affect choices. Lastly,
      practical concerns about the feasibility of accruing large numbers of subjects
      may drive trialists to specify bigger differences as clinically important, with a
      view to containing sample size requirements. We suggest that patients or other
      members of the public be given an active role in determining the magnitude of the
      clinically important treatment effect for trial planning. Probability trade-offs
      could be constructed to enable patients and/or healthy volunteers to indicate the
      degree of benefit they would want from a "new" treatment, given the potential
      side-effects of the same treatment. This method has the advantage of respecting
      patient autonomy and principles of informed consent. It provides an additional
      consideration when plausible effect sizes and error tolerances on hypothesis
      tests are balanced against feasibility of accruing various sample sizes. Its
      primary disadvantage is inconvenience, as it adds another step to trial design.
      On the other hand, if patient-based clinically important differences are
      generated for a variety of disease states and types of treatments, specific trade
      off exercises may be needed only for unusual trials.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7722593
TI  - Reliability of environmental and occupational exposure data provided by surrogate
      respondents in a case-control study of Parkinson's disease.
AB  - This study used data provided by 40 non-demented Parkinson's disease patients and
      101 community controls, and by their 110 spouses and 31 adult children to assess
      the reliability of surrogate-provided rural environmental and occupational
      exposure information on the index subjects. The level of overall raw agreement
      between the index subjects and the spouse or adult child surrogates varied from
      50.0 to 100.0% for the case-surrogate group and from 80.6 to 96.0% for the
      control-surrogate group. We did not detect significant differences in overall raw
      agreement between the case-surrogate and control-surrogate groups or between the
      spouse-surrogate and adult child-surrogate groups, for any of the variables
      studied. Considering all index subjects and their surrogates, the level of
      overall raw agreement was 80.3% for well water consumption, 82.3% for farm
      living, 85.8% for agricultural work, 87.1% for use of pesticides, 87.9% for field
      crop farming and 91.9% for use of fertilizers. However, the kappa estimates were
      lower, varying from 0.48 (SE = 0.20) for fertilizer use to 0.66 (SE = 0.11) for
      crop farming. The level of specific agreement was 52.2% for fertilizer use, 64.0%
      for pesticide use, 71.4% for agricultural work, 73.9% for crop farming, 80.9% for
      farm living, and 83.6% for well water consumption. The overall findings of this
      study support the use, if necessary, of spouses and adult children of index
      subjects as surrogate respondents in case-control studies of rural environment
      and occupational exposures and Parkinson's disease and, possibly, other
      neurologic diseases. Specific agreement seems to be a better index of reliability
      than overall agreement in studies where exposure is rare.

PMID- 7722594
TI  - Long-term physical functioning in persons with knee osteoarthritis from NHANES.
      I: Effects of comorbid medical conditions.
AB  - This study examined the effects of comorbid medical conditions (heart disease,
      pulmonary disease, hypertension and obesity) on the association of radiographic
      knee osteoarthritis (OA) with long-term difficulty in physical function. Data are
      from the National Health and Nutrition Examination Survey, 1971-1975 (NHANES I),
      a prospective epidemiologic cohort study, and the NHANES Epidemiologic Follow-up
      Study, 1982-1984 (NHEFS) and included 4059 persons who were 45-74 years old and
      participated in the detailed examination component of NHANES I. Knee OA was
      ascertained by anterior-posterior bilateral radiographs of the knee and self
      report of knee pain, heart and pulmonary disease by self report of disease or
      symptoms, and hypertension and obesity by blood pressure and weight measurements.
      The presence of symptomatic knee OA at NHANES I was associated with reported
      difficulty at NHEFS 1982-84 in functions which used the lower extremity
      (ambulation and transfer). The presence of coexistent chronic conditions,
      particularly heart disease, pulmonary disease and obesity, increased the
      likelihood of subsequent disability. These findings suggest that knee OA is
      associated with long-term physical disability, and that the presence of
      coexistent chronic disease may increase the amount of long-term disability from
      knee OA.

PMID- 7722595
TI  - Criticizing the critics: is peer-reviewing fair?

PMID- 7722596
TI  - Is peer-reviewing fair?

PMID- 7722597
TI  - Can the quality of peer review be measured?

PMID- 7722598
TI  - Relationship between hemoglobin and serum albumin.

PMID- 7722599
TI  - Alcohol and mortality: a review.
AB  - The relation of alcohol intake to total mortality is J-shaped. Abstainers have
      modestly higher mortality than moderate drinkers but considerably lower
      [corrected] mortality than heavy drinkers. The higher mortality among abstainers
      cannot be explained by selection or the presence of other risk factors. Known
      biologic mechanisms support the conclusion that moderate drinking increases the
      lifespan. No major differences have been found between the effects of beer, wine
      or liquor. While drinking patterns and changes in these influence mortality over
      time, little is known about their significance. The lowest risk of death seems to
      be at the average intake level of one drink per day. However, due to several
      sources of error in the assessment of alcohol intake no precise limits of optimal
      or safe drinking can be recommended. Trials are needed to ascertain these limits.
      Drinkers should practice moderation and watch for any harmful effects of alcohol.

PMID- 7722600
TI  - Decline in mortality from heart disease in Denmark: some methodological problems.
AB  - Mortality rates in Denmark from ischemic heart diseases (IHD), other heart
      diseases and unknown causes are presented for the period 1968-92. In all age
      groups, mortality from IHD is higher at the beginning of the period than at the
      end. For other heart disease, the plot of the mortality rate is U-shaped for the
      age groups 65-84 and > or = 85, but first decreases and is then constant for the
      age group 30-64. There are an increasing number of deaths from symptomatic heart
      disease. For the group of unknown causes, the rates are increasing for all sex
      and age groups. The relationship between deaths from IHD and deaths from unknown
      causes varies with period, age, sex and region. For women in Copenhagen in the
      age group 30-64, the mortality rate from unknown cause is higher than the rate
      for IHD at the end of period. Vital statistics must therefore be used cautiously
      in analysing trends for IHD, and even the validity of temporal changes within a
      country must be questioned.

PMID- 7722601
TI  - Item bias in cognitive screening measures: comparisons of elderly white, Afro
      American, Hispanic and high and low education subgroups.
AB  - A study of item bias in standard cognitive screening measures was conducted in a
      sample of Afro-American, Hispanic and non-Hispanic white elderly respondents who
      were part of a dementia case registry study. The methods of item-response theory
      were applied to identify biased items. Both cross-cultural and high and low
      education groups were examined to determine which items were biased. Out of 50
      cognitive items examined from six widely used cognitive screening measures, 16
      were identified as biased for either high and low education groups or
      ethnic/racial group membership.

PMID- 7722602
TI  - Determinants of pediatric day surgery cancellation.
AB  - Currently, most elective pediatric surgery is performed on an out-patient basis.
      The objective of this case-control study was to identify potential determinants
      of patient cancellation at a children's hospital. Cases were defined as patients
      that were canceled on the day of surgery, whereas controls were those patients
      who underwent surgery on the scheduled date. Demographic and clinical data were
      collected using chart review. Approximately 10% of all day surgery patients were
      canceled on the day scheduled for surgery, half for reasons deemed preventable.
      Of the preventable cancellations, stepwise logistic regression analysis showed
      that patients attending only the surgeon's office prior to day surgery, were more
      likely to be canceled because of inadequate preparation, compared to those
      patients attending both the surgeon's office and the hospital preoperative clinic
      (adjusted odds ratio = 3.18; 95% CI: 1.32, 7.63).

PMID- 7722603
TI  - Association between skin color and intraocular pressure in African Americans.
AB  - African Americans have a higher prevalence of elevated blood pressure and a
      higher prevalence of increased intraocular pressure (IOP). The blood pressure of
      African Americans has been found to be related to skin color. This study
      evaluated whether IOP was related to skin color. We measured IOP using a Tonopen
      and skin darkness using a spectrocolorimeter in 213 African Americans. Seventy
      patients were identified as systemic hypertensives. Spearman correlation
      coefficients were calculated to compare IOP and skin darkness. Mean IOP among
      hypertensives was 17.7 +/- 3.6 mmHg and among normotensives was 17.7 +/- 3.8
      mmHg. Mean IOP for the whole sample was 17.7 +/- 3.7 mmHg. No significant
      correlations were found between skin darkness and IOP among the normotensive and
      hypertensive groups (p = 0.52 and 0.44) nor for the sample as a whole (p = 0.33).
      Skin darkness as a measure of skin color in this sample population did not
      predict those subjects with higher IOPs.

PMID- 7722604
TI  - Alcohol and breast cancer.

PMID- 7722605
TI  - Spontaneous abortion and coronary heart disease.

PMID- 7722606
TI  - Breast implants: the tyranny of the anecdote.

PMID- 7722607
TI  - Silicone breast implants and long-term health effects: when are data adequate?
AB  - The epidemiological literature examining the possible association between
      silicone breast implants and breast cancer or rheumatological conditions or
      diseases is far greater today than it was when, in early 1992, FDA determined
      that the data were not adequate for the assessment of their safety. A literature
      data base exists for assessing the magnitude of risk for certain diseases that
      might be associated with silicone breast implantation and for narrowing the
      uncertainty in those estimates. The studies reported in this series make a major
      contribution to that database. As for future research needs, some general
      observations can be made. First, it is likely that completed, ongoing and planned
      studies will prove more than adequate in accurately delineating any cancer risks
      that might be associated with breast implantation. Second, the risks of
      developing scleroderma will also be reasonably well established. Further study
      may be desirable for other specific connective tissue diseases and for connective
      tissue disease considered as a whole.

PMID- 7722608
TI  - The prevalence of women with breast implants in the United States--1989.
AB  - Most estimates of the number of women with breast implants appear to be
      extrapolations of industry or clinical data. While both provide valuable
      information, the former about the total number of devices ever produced or sold
      and the latter about the cumulative number of surgeries performed, neither can be
      used to directly estimate the prevalence of women with silicone gel or saline
      implants. In 1989, Market Facts, Inc., conducted a mail survey of 40,000
      households chosen as representative of the population of the United States and
      received responses from 70.7%. Overall, the prevalence was 8.08 per 1,000 women
      with about 60% of the devices reportedly implanted for cosmetic reasons. The
      procedure was more common among Whites of the higher socio-economic classes.
      Based upon the results of this survey, the total number of US women in 1989 with
      breast implants was estimated to be 815,700 (95% confidence interval: 715,757
      924,729).

PMID- 7722609
TI  - Trends in the utilization of silicone breast implants, 1964-1991, and methodology
      for a population-based study of outcomes.
AB  - Using the unique data resources of the Rochester Epidemiology Project, we have
      designed a population-based retrospective cohort study to examine the risks and
      complications of silicone breast implants among 749 Olmsted County, Minnesota,
      women who received these devices between 1964 and 1991, and 1498 control women
      who did not receive such devices. In this paper, we present data describing the
      population-based trends in the utilization of these devices from 1964 to 1991. In
      addition, we discuss the case ascertainment, outcome assessment, and reliability
      of the data collection for the outcomes study. The utilization of breast implants
      increased markedly over the past 30 yr with the rate of new implants per 100,000
      women (> or = 15 years of age) rising from 3.5 in 1964 to 95 in 1979, remaining
      stable thereafter. The prevalence of breast implants among Olmsted County women >
      or = 15 years of age on 1 January 1992 was approx. 1%. An examination of the
      characteristics of these women reveals that recent utilization of breast implants
      has increased more rapidly among rural than among urban women, that the
      proportion of women receiving implants for breast cancer mastectomy
      reconstruction has increased in recent years, and that the great majority of
      women receiving implants are married at the time of implant. These trends also
      revealed that the average age of women who receive implants is rising and that in
      more recent years both much younger and much older women are receiving implants.

PMID- 7722610
TI  - Human breast sarcoma and human breast implantation: a time trend analysis based
      on SEER data (1973-1990).
AB  - Since the demonstration in the 1940s of foreign body induction of sarcomas in
      rodents, the safety of artificial implants in humans has been a matter of
      concern. In this study, we assess the risk for the development of breast sarcomas
      in women with silicone breast implants. Our analysis is based on the National
      Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program
      database for the years 1973-1990 and on estimates of breast implantation rates
      from about 1960 onward. We have divided the SEER data into two equal time
      periods, 1972-1981 and 1982-1990. For each time period, we estimated the average
      annual number of women in the United States who had received breast implants 10
      or more years earlier. This analysis allows for a 10 year latency period for the
      induction of breast sarcoma. We calculated that the average number of women in
      the U.S. 10 or more years post breast implantation was 55,000 for the 1973-1981
      period and 509,000 for the 1982-1990 period. We then examined the SEER data to
      observe whether there was a concomitant rise in the female breast sarcoma
      incidence rates between these two time periods. We found the mean age-adjusted
      incidence rate of breast sarcomas was 0.13 per 100,000 women for the initial 9
      year period, 1973-1981, and 0.12 per 100,000 women for the latter 9-year period,
      1981-1990.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722611
TI  - Artificial implants and soft tissue sarcomas.
AB  - The carcinogenic potential of artificial implants has been of concern in recent
      years. Case reports and animal studies, dating back to the 1950s, have reported
      possible associations between artificial implants and soft tissue sarcomas, but
      epidemiologic data have been lacking. In a recent study of soft tissue sarcomas
      and military service, data on artificial implants were collected but not
      presented. This paper examines a possible association between artificial implants
      and soft tissue sarcomas.

PMID- 7722612
TI  - Epidemiologic follow-up studies of breast augmentation patients.
AB  - Although hundreds of thousands of women in this country have had augmentation
      mammaplasty, little is known about long-term effects. Clinical studies have
      documented a decreased ability to detect breast lesions in women with implants,
      leading to concerns regarding breast cancer risk. There is also anecdotal
      evidence that implants might have effects on a variety of immune conditions. More
      recently, concern over carcinogenic effects has heightened given findings that
      the polyurethane foam, used in a minority of implants to envelope silicone gel,
      contains chemicals linked to cancer in laboratory animals. Only a few
      epidemiologic studies on long-term effects have been published, and all have had
      methodologic limitations, including the possibility of inappropriate comparison
      rates, limited and/or incomplete follow-up, absence of information on patients
      characteristics, and lack of specific information on types of implanted material.
      Several case-control and cohort studies are currently underway which are
      attempting to overcome methodologic limitations of previous studies. Past
      descriptive and analytic studies are reviewed. In addition, ongoing follow-up
      efforts are discussed, with attention given to the methodologic adjuncts
      necessary for allowing valid assessments of long-term disease effects.

PMID- 7722613
TI  - Frequency of augmentation mammoplasty in patients with systemic sclerosis: data
      from the Johns Hopkins-University of Maryland Scleroderma Center.
AB  - The objective was to determine the frequency of augmentation mammoplasty in
      female patients with systemic sclerosis (SSc). Female patients with a clinical
      diagnosis of SSc were identified from the registry of the Johns Hopkins
      University of Maryland Scleroderma Center, Washington D.C. Chapter of the
      Scleroderma Foundation, and files of practicing rheumatologists in the Baltimore
      Washington metropolitan area. A pretested questionnaire was mailed to all
      eligible cases. Of 339 cases, 210 (62%) returned completed questionnaires. Three
      cases reported augmentation mammoplasty with silicone gel-filled prosthesis: 2
      (1%) prior to and 1 (0.5%) after physician-diagnosis of SSc. The frequency of
      augmentation mammoplasty prior to physician-diagnosis of SSc of 9.5 per 1000 does
      not appear to differ from the expected frequency of 3.3-8.2 per 1000 derived from
      national population samples. A well-designed case-control study with population
      based controls and adequate statistical power is being conducted to examine this
      possible association.

PMID- 7722614
TI  - Breast implants, rheumatoid arthritis, and connective tissue diseases in a
      clinical practice.
AB  - This study was designed to assess the relationship between breast implants and
      certain rheumatologic diseases (rheumatoid arthritis and diffuse connective
      tissue diseases). The study base was a rheumatological practice in Atlanta,
      Georgia that started in 1982 and began computerizing its records in 1985. The
      computerized records through May 1992 included 4229 women patients, 150 with
      breast implants and 721 with a diagnosis of rheumatoid arthritis (RA) and/or one
      of the connective tissue diseases (CTDs). Of the 721 patients who had been
      diagnosed as having rheumatoid arthritis (RA) and/or one of the connective tissue
      diseases (CTDs), 392 had rheumatoid arthritis, 344 had connective tissue disease,
      15 had both rheumatoid arthritis and a connective tissue disease, and 33 had more
      than one connective tissue disease. Of the patients with connective tissue
      disease, 179 had systemic lupus erythematosus, 64 had scleroderma, 49 had
      Sjogren's syndrome, 36 had dermatomyositis or polymyositis, and 49 had mixed
      connective tissue disease. Data were analyzed by univariate and multivariate
      techniques including logistic regression. Significant variables included age at
      first visit, income strata, and period of first visit. Analyses were performed
      for each clinical diagnosis, for all connective tissue diseases together (CTDs),
      and for those with rheumatoid arthritis and/or connective tissue disease
      (RA/CTD). Analyses were performed on the total data base and on the records of
      new patients (1986-1992). The adjusted odds ratio for breast implants among women
      who entered the practice in 1986-1992 and were diagnosed as having rheumatoid
      arthritis and/or one of the connective tissue diseases (RA/CTDs) was 0.45 (0.22
      0.90), for those with rheumatoid arthritis was 0.61 (0.28-1.49), for those with
      any of these specific diffuse connective tissue diseases was 0.34 (0.11-1.06)
      compared to those without the disease. For systemic lupus erythematosus, the odds
      ratio of 0.24 (0.03-1.75) was based on a single case who had the disease 5 yr
      before the implant. For Sjogren's syndrome, the odds ratio was 1.67 (0.39-7.13)
      based on two cases, one of whom had the disease 5 yr before the implant. The
      calculated odds ratios for scleroderma, dermatomyositis/polymyositis, and mixed
      connective tissue disease were zero since no cases were diagnosed among the
      patients with breast implants. This study found no evidence that women with
      breast implants are at an increased risk for having rheumatoid arthritis or other
      diffuse connective tissue disease.

PMID- 7722615
TI  - The design of a population-based case-control study of systemic sclerosis
      (scleroderma): commentary on the University of Michigan study.

PMID- 7722616
TI  - Developmental kinetics of GAD family mRNAs parallel neurogenesis in the rat
      spinal cord.
AB  - GABA (gamma-amino butyric acid), a fast-acting synaptic transmitter in the mature
      CNS, is synthesized from glutamate by GAD (glutamic acid decarboxylase). We have
      developed an ultrasensitive PCR technique to quantify the expression of GAD
      related mRNAs during the development of the rat cervical spinal cord and have
      localized them using in situ hybridization. GAD65, GAD67, and an alternatively
      spliced variant of GAD67, EP10, were quantified each day from embryonic (E) day
      11 through E21, and at postnatal days 0, 7, 14, and adult. GAD65 and GAD67 mRNAs
      were detected at E11 and increased exponentially over three orders of magnitude
      during embryonic development, then declined approximately threefold in the first
      2 postnatal weeks. While the exponential growth phase coincided with the
      progressive appearance of GAD67 in situ signals in both the ventral and dorsal
      cord, the postnatal decline coincided with the virtual disappearance of
      expression in the ventral region. EP10 expression was prominent in the embryo,
      then declined markedly together with the mRNA encoding the neuroepithelial stem
      cell marker, nestin. The concerted appearance of GAD-related mRNAs paralleled
      transcripts encoding neuronal markers (light and heavy neurofilaments) and also
      closely correlated with the expression of GABA, mRNAs encoding GABAA receptor
      subunits, and depolarizing responses to GABA. We have used the results on GAD
      related mRNA expressions to formulate a simple, minimal mathematical model that
      accounts for their kinetics in terms of positive and negative feedback loops.

PMID- 7722617
TI  - Inositol 1,4,5-trisphosphate and ryanodine receptor distributions and patterns of
      acetylcholine- and caffeine-induced calcium release in cultured mouse hippocampal
      neurons.
AB  - The distributions of inositol 1,4,5-trisphosphate and ryanodine receptors (InsP3R
      and RyR) and the patterns of increase in intracellular calcium ion concentration
      ([Ca2+]i) elicited by their activation were compared in cultured hippocampal
      neurons. InsP3R and RyR were labeled using specific antibodies and formed small
      aggregations in the somata and dendrites of pyramidally shaped neurons. Both
      receptors were densest in somata. In dendrites the InsP3R and RyR were not
      distributed homogeneously; InsP3R was found in all regions, while RyR was least
      dense in fine processes. Increases in [Ca2+]i elicited by acetylcholine (to
      activate InsP3 receptors via muscarinic receptors) and caffeine (to stimulate
      ryanodine receptors) were measured in dendrites using Ca(2+)-sensitive
      fluorescent dyes and confocal microscopy. Ca2+ responses to acetylcholine were
      transient and observed in proximal and distal dendritic regions. In contrast,
      caffeine-induced responses were sustained and restricted to proximal dendrites.
      Thus the patterns of calcium release in fine dendrites mirrored the distributions
      of InsP3R and RyR. Calcium responses to both acetylcholine and caffeine were
      observed in the absence of external calcium and thus were dependent on Ca2+
      release. Ca2+ responses showed localized fluctuations and variations in response
      delay times. Sequential activation of InsP3R and RyR in somata resulted in mutual
      occlusion of Ca2+ release. The existence of InsP3-gated and Ca(2+)-induced Ca2+
      release as spatially distinct, but mutually interacting, mechanisms may be
      important in the generation of oscillations and propagating Ca2+ waves in somata
      and dendrites of hippocampal neurons.

PMID- 7722618
TI  - Axonal activation-induced calcium transients in myelinating Schwann cells,
      sources, and mechanisms.
AB  - We have investigated the role of myelinating glia in events associated with
      propagation of the action potential at nodes of Ranvier using combinations of
      optical and electrophysiological recording methods. Calcium transients were
      observed in Schwann cells by fluorescent imaging of the nodal complex of fibers
      loaded with the calcium-sensitive dye fluo3-AM. To follow [Ca2+]i changes
      associated with neuronal activity at the node of Ranvier, nerves loaded with
      fluo3 were imaged during axonal activation using laser-scanning confocal
      microscopy. To elucidate sources of [Ca2+]i transients, we tested the effects of
      drugs known to alter [Ca2+]i. [Ca2+]i transients in Schwann cells were observed
      in response to axonal activation and these were subsequently blocked by ryanodine
      if ryanodine was present during a previous [Ca2+]i transient. Bath applications
      of caffeine induced [Ca2+]i transients which could be blocked by ryanodine. These
      findings indicate that calcium-activated calcium release occurs in Schwann cells
      in response to impulse activity.

PMID- 7722619
TI  - Physiological subgroups of nonpyramidal cells with specific morphological
      characteristics in layer II/III of rat frontal cortex.
AB  - Physiological and morphological properties of nonpyramidal cells in layer II/III
      of frontal cortex of young rats were studied in vitro by whole-cell recording and
      intracellular staining with biocytin. Layer II/III nonpyramidal cells could be
      divided into four subgroups by their firing patterns in response to depolarizing
      current pulses and their patterns of dendritic and axonal arborizations. (1) Fast
      spiking (FS) cells (35% of the total sample) showed an abrupt episode of
      nonadapting repetitive discharges of shorter-duration action potentials. FS cells
      had local and horizontal axonal arbors which did not enter layer I. This type of
      FS cell was immunoreactive for parvalbumin and included some basket cells. Three
      chandelier cells were identified as FS cells, although one chandelier cell was
      not identified as an FS cell. (2) Late-spiking (LS) cells (11%) exhibited slowly
      developing ramp depolarizations near threshold. LS cells were neurogliaform
      cells. (3) Low-threshold spike (LTS) cells (5%) had prominent low-threshold
      spikes when stimulated from hyperpolarizations. The main axons of LTS cells
      ascended, and the collaterals entered into layer I. (4) The remaining cells
      [regular-spiking nonpyramidal (RSNP) cells] (49%) could not be categorized into
      the above three subgroups. In some RSNP cells depolarizing pulses from
      hyperpolarizations induced fast depolarizing notches with small amplitude. RSNP
      cells had vertically elongated axonal fields, extending from layer I to V,
      sometimes to layer VI. This subgroup included double bouquet cells and bipolar
      cells. Each subgroup with a different firing mode may differentially contribute
      to neocortical laminar and columnar circuitry.

PMID- 7722620
TI  - Neurotrophin-4/5 (NT-4/5) and brain-derived neurotrophic factor (BDNF) act at
      later stages of cerebellar granule cell differentiation.
AB  - The developing cerebellum expresses genes which encode for both neurotrophins and
      their receptors. The present study was designed to determine at what stages
      during cerebellar granule cell neurogenesis neurotrophin family molecules may
      act. We report here that in purified, well-characterized granule cell cultures
      (Gao et al., 1991; 1992), none of the neurotrophins stimulated proliferation of
      granule cell precursors or rescued phenotypic defect of mutant weaver granule
      cell precursors in the initiation of neuronal differentiation. However,
      neurotrophin-4/5 (NT-4/5) and BDNF, but not neurotrophin-3 (NT-3) or NGF,
      promoted neurite extension and survival of differentiated cerebellar granule
      cells. Both of these effects were blocked by the specific inhibitor for Trk
      tyrosine kinases, K-252a. NT-4/5 and BDNF also enhanced neurite extension by
      weaver granule cells which were rescued by wild-type granule cells during
      differentiation. Moreover, TrkB immunohistochemistry performed on sections of the
      developing wildtype and weaver cerebella revealed that only differentiated
      granule cells, but not the precursor cells, make high levels of TrkB receptor.
      These findings together suggest that NT-4/5 and BDNF promote the maturation and
      maintenance of differentiated granule cells, effects which are downstream to the
      weaver gene. Since no additive effects were seen with the combination of NT-4/5
      and BDNF, it seems likely that the two neurotrophins activate the same receptor
      trkB for signal transduction.

PMID- 7722621
TI  - Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat
      retinal bipolar cell terminals.
AB  - Inhibitory effects of GABA on K(+)-evoked Ca2+ influx into rat retinal bipolar
      cell terminals were studied using calcium imaging methods. Application of high K+
      evokes a sustained, reversible increase in [Ca2+]i at bipolar cell terminals,
      which occurs mainly via dihydropyridine-sensitive (L-type) Ca2+ channels. There
      are at least two GABA receptor subtypes coexisting at bipolar cell terminals: a
      conventional GABAA receptor and a bicuculline/baclofen-insensitive GABA receptor.
      Activation of either GABA receptor inhibited the K(+)-evoked Ca2+ response.
      However, these two GABA receptor subtypes have distinct properties. GABAA
      receptors suppress the Ca2+ response only at relatively high concentrations of
      agonist, and with fas kinetics and a narrow dynamic range. In contrast, the
      bicuculline/baclofen-insensitive GABA receptors produce inhibition on the Ca2+
      response at a much lower concentration of agonist, and with slow onset and a
      wider dynamic range. The pharmacologic profile of the bicuculline/baclofen
      insensitive GABA receptor at bipolar cell terminals is most similar to the GABAC
      receptor reported by Feigenspan et al. (1993). Unlike the GABAC receptors
      described in other species, it is extremely insensitive to picrotoxin. Therefore,
      it may be appropriate to refer to this receptor as a picrotoxin-insensitive GABAc
      receptor. 3-Aminopropyl(methyl)phosphinic acid (3-APMPA) and 3
      aminopropylphosphonic (3-APA), two phosphate analogs of GABA, selectively
      antagonize the picrotoxin-insensitive GABAc receptors but not the GABAA receptors
      in this system. These results imply a functional role for multiple GABA receptors
      in regulating synaptic transmission at bipolar cell terminals.

PMID- 7722622
TI  - Immune challenge and immobilization stress induce transcription of the gene
      encoding the CRF receptor in selective nuclei of the rat hypothalamus.
AB  - The present study investigated the effect of intraperitoneal (i.p.)
      administration of endotoxin lipopolysaccharide (LPS) and immobilization stress on
      the genetic expression of corticotropin-releasing factor receptor (CRF-R) in the
      brains of conscious male Sprague-Dawley rats. One group of rats was killed at 1,
      3, 6, 9, and 12 hr after a single intraperitoneal injection of either the LPS
      (250 micrograms/100 gm of body weight) or the vehicle solution; the other group
      was killed before, immediately after, 1.5, 3, 6, and 12 hr after a 90 min acute
      session of immobilization stress. Rats were deeply anesthetized and rapidly
      perfused with a solution of 4% paraformaldehyde-borax. Frozen brains were mounted
      on a microtome and cut from the olfactory bulb to the medulla in 30 microns
      coronal sections. mRNA encoding the rat CRF-R was assayed by in situ
      hybridization histochemistry using a 35S-labeled riboprobe, and CRF-R
      localization within CRF-immunoreactive neurons in the PVN was determined using a
      combination of immunocytochemistry and in situ hybridization techniques. Strong
      basal levels of CRF-R transcripts were observed in several regions of the brain
      (piriform cortex, medial and basolateral nuclei of the amygdala, red nucleus,
      pontine gray, cerebellum, laterodorsal tegmental nucleus, caudal division of the
      zona incerta, nucleus incertus, spinal and principal sensory nuclei of the
      trigeminal nerve, and various layers of the cortex). A low to moderate signal was
      also detected in multiple sites (medial septal nucleus, nucleus of the diagonal
      band, supraoptic nucleus, arcuate nucleus of the hypothalamus, interpeduncular
      nucleus, and nucleus prepositus). Whereas vehicle-treated and control rats
      displayed hardly detectable signals of CRF-R mRNA in the paraventricular nucleus
      (PVN), CRF-R gene transcription was highly stimulated by LPS administration and
      immobilization stress in this hypothalamic structure. Indeed, the CRF-R mRNA
      signal was positive in the dorsomedial parvocellular PVN 3 hr after LPS
      injection, strong and maximum in both parvo- and magno-PVN at 6 hr postinjection,
      and declined 9 and 12 hr after treatment. Similarly, 90 min and 3 hr after the
      immobilization session, mRNA encoding the CRF-R was highly expressed in the parvo
      PVN and totally vanished 12 hr after the stress. A lower but significant increase
      in the CRF-R transcript signal was also observed in the supraoptic nucleus 6 hr
      after the LPS treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7722623
TI  - Cholinergic regulation of [Ca2+]i during cell division and differentiation in the
      mammalian retina.
AB  - Transmitter-like molecules are thought to influence many aspects of neuronal
      development, often by regulating the levels of intracellular calcium. Using the
      Ca2+ sensitive dye, fura-2, this study demonstrates that in the rabbit retina,
      ACh analogs stimulate a rise in cytosolic free Ca2+ concentration ([Ca2+]i) in
      many cell types, and in cells at various stages of differentiation during
      embryonic and neonatal development. The elevation in [Ca2+]i in cells within the
      ventricular zone (VZ) resulted primarily from the activation of muscarinic
      receptors. By contrast, the cholinergic regulation of [Ca2+]i of ganglion cells
      and amacrine cells, cell types which migrate to their final destinations early in
      fetal life, was largely mediated by nicotinic receptors. The muscarinic response
      of the VZ cells was mediated by the M1, rather than the M2-type of muscarinic
      receptor. This response was abolished in the absence of extracellular Ca2+ and in
      the presence of NiCl2, but it was not affected by verapamil or omega-conotoxin,
      thus suggesting that while Ca2+ influx occurred, it did not involve L- and N-type
      voltage-gated Ca2+ channels. The muscarinic response in the VZ disappeared at the
      end of the period of cell division in the retina, just prior to eye opening. By
      contrast, nicotinic-induced changes in [Ca2+]i in ganglion cells and amacrine
      cells persisted throughout development. Since previous studies have implicated
      that the precursors of ganglion cells and amacrine cells also possess muscarinic
      receptors (Yamashita and Fukuda, 1993), the concomitant emergence of different
      functional cholinergic receptor (AChR) subtypes with differentiation in vivo
      suggests that ACh may play diverse and temporally regulated roles in the
      developing retina.

PMID- 7722624
TI  - Distribution of the excitatory amino acid receptor subunits GluR2(4) in monkey
      hippocampus and colocalization with subunits GluR5-7 and NMDAR1.
AB  - Ionotropic excitatory amino acid (EAA) receptors are divided pharmacologically
      into three categories termed NMDA, AMPA/kainate, and high affinity kainate
      receptors. Each of these receptor subtypes is composed of a specific subset of
      subunits termed GluR1-4 (AMPA/kainate), GluR5-7, KA1-2 (high affinity kainate),
      and NMDAR1, 2 A-D (NMDA). Although colocalization of NMDA and non-NMDA receptors
      has been previously demonstrated electrophysiologically in rat, comprehensive
      analyses of subunit specific colocalization patterns have not been possible until
      the advent of appropriate antibodies. The present study investigates such
      immunocytochemical colocalization of several EAA receptor subunits within
      individual cells as well as dendritic spines in the monkey hippocampus. Double
      label immunohistochemical experiments using antibodies which are specific for
      GluR2(4), GluR5-7, and NMDAR1 demonstrated that virtually all projection neurons
      in each subfield of the hippocampus contain subunits from the AMPA/kainate,
      kainate, and NMDA receptor families. In addition, confocal microscopy has
      demonstrated that individual spines may contain subunits representative of
      multiple EAA receptor families. Furthermore, detailed regional, cellular, and
      ultrastructural distribution patterns of the EAA receptor subunits GluR2 and
      GluR4 in monkey hippocampus are presented based on the use of a monoclonal
      antibody (mAb), 3A11, which was generated against the putative extracellular N
      terminal domain of GluR2. Since this antibody recognizes only GluR2 in Western
      blots, and GluR2 as well as GluR4 in fixed transiently transfected cells, it has
      been designated anti-GluR2(4). Immunocytochemical labeling with mAb 3A11 revealed
      pyramidal cell somata and dendrites in each field of the hippocampus, as well as
      granule cells and polymorphic hilar cells in the dentate gyrus. Small cells with
      the morphologic characteristics of astroglia were also immunolabeled for GluR2(4)
      within the alveus and fimbria. Immunoreactivity at the ultrastructural level was
      localized to postsynaptic densities on dendritic spines and shafts and within the
      somatodendritic cytoplasm in all major hippocampal regions, as well as in a
      subset of dentate granule cell axons within the mossy fiber projection.

PMID- 7722626
TI  - Magnetic and electric brain activity evoked by the processing of tone and vowel
      stimuli.
AB  - Sustained magnetic and electric brain waves may reflect linguistic processing
      when elicited by auditory speech stimuli. In the present study, only in the
      latency interval subsequent to the N1m/N1 has a sensitivity of brain responses to
      features of speech been demonstrated. We conclude this from studying the auditory
      evoked magnetic field (AEF) and the corresponding evoked potential (AEP) in
      response to vowels and a tone. Brain activity was recorded from the left and the
      right hemisphere of 11 subjects. Three aspects of transient activity were
      examined: (1) the amplitudes and source characteristics of the N1m component of
      the AEF; (2) the amplitudes and source characteristics of the sustained field
      (SF), and (3) the corresponding amplitude characteristics of the AEP. Sustained
      potential amplitudes and SF root mean square amplitudes, as well as the dipole
      strength of the SF source, were found to be larger for vowel-evoked signals than
      for signals elicited by the tone stimulus. The amplitude and dipole strength
      effects had an interaction with hemisphere, with larger interhemispheric
      differences for the vowel condition, as well as larger tone-vowel differences of
      these parameters in the speech-dominant left hemisphere. No statistically
      significant hemisphere-by-stimulus-type interactions were found in N1/N1m
      amplitudes and N1m source parameters.

PMID- 7722625
TI  - GABAA/benzodiazepine receptors in acutely isolated hippocampal astrocytes.
AB  - The properties of GABA receptor-mediated responses were examined in noncultured
      astrocytes, acutely isolated from the mature rat hippocampus. Whole-cell patch
      clamping revealed a GABA-activated Cl- conductance that was mimicked by the GABAA
      receptor agonist muscimol and depressed by the GABAA antagonists bicuculline and
      picrotoxin. The GABAA-activated currents were potentiated by the barbiturate
      pentobarbital and the benzodiazepine diazepam. The benzodiazepine inverse agonist
      DMCM either enhanced or depressed the astrocytic GABAA-mediated responses,
      suggesting receptor heterogeneity with respect to pharmacologic profiles. In
      addition, GABA evoked an increase in [Ca2+]n measured by indo-1 fluorometry,
      which was depressed in the presence of verapamil or picrotoxin. A GABAA-induced
      depolarization, therefore, causes Ca2+ influx through voltage-gated Ca2+
      channels. The expression and subcellular localization of GABAA receptors and its
      subunits were examined using immunohistochemical and fluorescent benzodiazepine
      binding techniques. Polyclonal antisera raised against the GABAA/benzodiazepine
      receptor, which recognizes multiple subunit isoforms, labeled receptors on the
      astrocytic cell body and most large processes. In contrast, antisera generated
      against either alpha 1 or beta 1 subunit peptides revealed immunoreactivity
      predominantly on a subset of processes. To determine the subcellular distribution
      of membrane-bound receptors, a fluorescent benzodiazepine derivative was
      superfused over live astrocytes and visualized with laser-scanning confocal
      microscopy. Specific fluorescence was distributed in discrete clusters on the
      cell soma and a subset of distal processes. Collectively, these data support the
      view that astrocytes, like neurons, express GABAA receptors and target subunit
      isoforms to distinct cellular localizations. Astrocytic GABAA receptors may be
      involved in both [Cl-]o and [pH]o homeostasis, and a GABA-evoked increase in
      [Ca2+]i could serve as a signal between GABAergic neurons and astrocytes.

PMID- 7722627
TI  - Cyclooxygenase inhibition and the spinal release of prostaglandin E2 and amino
      acids evoked by paw formalin injection: a microdialysis study in unanesthetized
      rats.
AB  - Injection of formalin into the hind paw evokes a biphasic flinching of the
      injured paw. Pharmacological characterization of this behavior has implicated the
      spinal release of excitatory amino acids (EAAs) and cyclooxygenase (COX)
      products. To address this hypothesis, we examined the effect of paw formalin
      injection on release of EAAs and prostaglandin E2-like immunoreactivity (PGE2-LI)
      from the spinal cord in unanesthetized rats using a dialysis probe placed in the
      lumbar subarachnoid space. To assess the contribution of spinal COX products, the
      effects of S(+)- and R(-)-ibuprofen (active and inactive COX inhibitors) were
      examined. Paw formalin injection evoked a biphasic spinal release of PGE2-LI with
      an increase above resting concentrations of 110% in the 0-10 min sample, and of
      83% in the 20-30 min sample. Significantly increased release of glutamate (Glu;
      110%) and aspartate (Asp; 112%) was only observed in the 0-10 min sample. Saline
      injection into the paw had no effect on behavior, PGE2-LI, or EAA release.
      Intraperitoneal administration of 10 mg/kg, but not 1 mg/kg, S(+)-ibuprofen
      reduced paw flinching, blocked the elevated levels of PGE2-LI, and suppressed Glu
      and Asp release to 50% of control. Intrathecal delivery of 10 micrograms, but not
      1 microgram, S(+)-ibuprofen also suppressed formalin-induced behavior, PGE2-LI,
      Glu, and Asp release. R(-)-ibuprofen showed no effect on formalin-induced
      behaviors or spinal release. These data demonstrate that paw formalin injection
      produces spinal release of PGE2-LI corresponding to the biphasic behavioral
      response and that the evoked release is blocked by antinociceptive doses of COX
      inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722628
TI  - IPSPs strongly inhibit climbing fiber-activated [Ca2+]i increases in the
      dendrites of cerebellar Purkinje neurons.
AB  - The interaction between the excitatory climbing fiber (CF) response and stellate
      cell inhibition was studied in guinea pig Purkinje cells in sagittal slices from
      the cerebellar vermis. Sharp microelectrode recordings from the soma or dendrites
      were combined with high-speed fluorescence imaging of intracellularly injected
      fura-2. In this way both the electrical responses and the associated [Ca2+]i
      changes could be monitored at the same time. Usually simultaneously activated
      inhibition caused almost no change to the somatically recorded CF response.
      However, the inhibition caused a strong reduction in the CF-associated [Ca2+]i
      increase which normally was widespread in the dendrites. This effect was graded;
      stronger inhibition caused a larger and more widespread reduction in the [Ca2+]i
      change that was greatest in the more distal dendrites. Sometimes the reduction
      was over 90% in the distal dendrites and occasionally it was localized to only a
      single dendritic branch. Both the inhibitory postsynaptic potential (IPSP) and
      the associated reduction in the CF-induced [Ca2+]i change were blocked by
      bicuculline, a GABAA receptor antagonist. Dendritic recordings showed that each
      CF response evoked a 2-3 msec wide action potential. The amplitude of this action
      potential was reduced in a graded manner by the IPSP in parallel with the
      reduction in the [Ca2+]i change. Varying the time between the activation of the
      IPSP and the CF response showed that both the reduction in the [Ca2+]i change and
      the action potential amplitude occurred in a narrow time window of about 8-10
      msec, about the rise time of the IPSP. Together these results indicate that the
      CF response activates a fast dendritic Ca2+ spike that causes most of the [Ca2+]i
      increase, both of which can be blocked by an inhibitory shunting conductance.
      This interaction provides a means whereby Ca(2+)-dependent dendritic mechanisms
      can be modulated without affecting the immediate output of the Purkinje cell.

PMID- 7722629
TI  - Development of memory and the hippocampus: comparison of food-storing and
      nonstoring birds on a one-trial associative memory task.
AB  - Food-storing birds, for example, marsh tits, Parus palustris, use memory to
      retrieve stored food and have a larger hippocampus relative to the rest of the
      telencephalon than do species that store little or no food such as the blue tit,
      P. caeruleus. The difference between food storers and nonstorers in relative
      hippocampal volume occurs after the young birds have fledged from the nest and is
      dependent upon some aspect of memory for retrieving caches of stored food. To
      test whether or not species differences in memory and volumetric changes in the
      hippocampus could be triggered by experience of memory tasks other than retrieval
      of stored food, groups of hand-raised marsh tits and blue tits were tested
      between days 35 and 192 posthatch on a one-trial associative memory task in which
      they were rewarded in phase II for returning to the feeder where they had eaten
      part of a peanut 20 min earlier. No species differences were found when the
      peanut was visible in phase I, but when the peanut was hidden in phase I, marsh
      tits performed better than blue tits, irrespective of whether or not they had had
      previous experience of storing and retrieving food. In dissociation trials
      (transformed array of feeders), marsh tits with food-storing experience responded
      preferentially to spatial cues, whereas blue tits responded equally to both
      spatial position and object-specific cues. These species differences are also
      found in wild-caught adults. However, marsh tits without food-storing experience
      responded equally to both spatial position and object-specific cues, which
      suggests that experience of storing and/or retrieving caches is required in order
      for marsh tits to develop the spatial preference seen in adult food storers. Both
      marsh tits with experience of the one-trial associative memory task and those
      that had also had food-storing experience had larger relative hippocampal volumes
      than did controls, independent of age. Of the marsh tits trained on the one-trial
      associative memory task, there was no difference between those that had had food
      storing experience and those that had not. However, in blue tits, there was no
      effect of experience on relative hippocampal volume. No volumetric differences
      were observed in ectostriatum, which served as a control brain region. The
      results suggest that some aspect of memory for retrieving food (whether or not
      stored by the bird) directly influences growth of the hippocampal region in marsh
      tits, the food-storing species, but not in blue tits, the nonstoring species.

PMID- 7722630
TI  - A critical band filter in touch.
AB  - Separate mechanoreceptor systems in humans were isolated by varying the spectra
      of vibrotactile stimuli. First, the function relating threshold to frequency of a
      sinusoid was obtained on the fingertip for each of four subjects, and it was
      found to comprise two limbs: a Pacinian and a non-Pacinian limb. The peak
      sensitivity within the Pacinian limb (mediated by Pacinian corpuscles) was around
      250 Hz and spanned the region from 65 to 400 Hz. The non-Pacinian limb showed no
      detectable change in sensitivity in the region between 10 and 65 Hz. These two
      limbs were then treated as psychophysical channels in experiments in which narrow
      band noise and individual sinusoids were used to excite one or both channels. In
      the second and third experiments, the noise stimuli varied in bandwidth from 8 to
      70 Hz and varied in center frequency from 25 to 218 Hz. Masking functions were
      obtained for ON-frequency conditions (the sinusoidal test and noise masker
      occupied the same frequency region) and for OFF-frequency conditions (the test
      and masker occupied different frequency regions). The ON-frequency experiments
      were used to estimate the signal-to-noise ratio (S/N) of the Pacinian channel at
      threshold. The OFF-frequency masking experiments were used to infer the shape of
      the Pacinian channel at frequencies below 65 Hz, where thresholds for Pacinian
      activation were above detection threshold. The results of these three experiments
      predicted the findings of a fourth masking experiment with a parameter free model
      that treated the Pacinian channel as a filter that integrates stimulus power. The
      results show that the Pacinian channel is analogous to a critical band in the
      auditory system.

PMID- 7722631
TI  - Somatic gene transfer of NGF to the aged brain: behavioral and morphological
      amelioration.
AB  - Primary fibroblasts modified to secrete nerve growth factor (NGF) were implanted
      into the nucleus basalis magnocellularis (NBM) of aged memory impaired rats. The
      NGF-producing fibroblasts survived for 6 weeks following transplantation and
      continued expressing NGF mRNA through the duration of the experiment. A
      significant amelioration of the memory impairment and a significant increase in
      size and number of low-affinity NGF receptor (p75)-positive neurons in the basal
      forebrain were observed. Implantation of NGF-producing cells into normal young
      adult rats resulted in a transient but significant memory impairment and
      hypertrophy of low-affinity NGF receptor-positive neurons. These results show
      that naturally occurring age-related memory loss can be reversed by grafting
      cells engineered to secrete NGF directly to the NBM, and that either cholinergic
      hyper- or hypofunction may lead to cognitive impairments.

PMID- 7722632
TI  - Spontaneous quantal transmitter secretion from myocytes and fibroblasts:
      comparison with neuronal secretion.
AB  - When exogenous ACh is loaded into the cytoplasm of cultured amphibian myocytes
      and fibroblasts, the cells undergo spontaneous quantal ACh secretion, as detected
      by the appearance of pulsatile membrane currents in Xenopus myocytes which are
      manipulated into contact with the cells. These currents resemble in many ways the
      miniature endplate currents (MEPCs) observed at developing neuromuscular synapses
      formed on these Xenopus myocytes. Analyses of the frequency, amplitude, and time
      course of these currents suggests similarity in the cellular mechanisms involved
      in the packaging and secretion of ACh quanta in fibroblasts, myocytes, and
      developing neurons. The size of the ACh packets released by the non-neuronal
      cells were found to be very similar to the size of the neuronal ACh quanta, which
      are thought to result from the exocytotic release of synaptic vesicles. Moreover,
      the kinetics with which the ACh packets are discharged from all three cell types
      are comparable, although the speed of secretion in non-neuronal cells is somewhat
      slower and more irregular. The spontaneous quantal ACh secretion from neurons and
      myocytes was decreased by reducing cytosolic Ca2+ level and enhanced by
      activation of protein kinase C with phorbol ester, but secretion from fibroblasts
      was unaffected by both treatments. The spontaneous secretion from fibroblasts did
      show some sensitivity to a rise in cytosolic Ca2+ after treatment with a Ca2+
      ionophore. These observations support the hypothesis that the basic machinery for
      transmitter secretion operating in neurons derive from a more ubiquitous
      mechanism used for constitutive secretion and membrane trafficking in non
      neuronal cells, and neuronal differentiation involves expression of additional
      unique components for the regulation of the spontaneous quantal secretion.

PMID- 7722633
TI  - Neurexins are differentially expressed in the embryonic nervous system of mice.
AB  - Expression of the major isoforms of three neurexin genes was analyzed in the
      developing embryonic nervous system of mice by Northern blot and in situ
      hybridization. Transcripts of all three genes were detected as early as embryonic
      day 10 (E10) and increased with maturation of the nervous system. RNAs of the
      major neurexin isoforms (alpha and beta) were found throughout the central
      nervous system exclusively in postmitotic neurons and at least 1 d before
      synapses are formed. In contrast, in the PNS the alpha- and beta-isoforms
      displayed differential expression patterns. Neurexin III mRNA showed a more
      restricted regional expression than neurexin I and II transcripts. These
      expression profiles are consistent with the hypothesis that the neurexins have a
      function in early neuronal differentiation and axogenesis.

PMID- 7722634
TI  - N-acetylcysteine (D- and L-stereoisomers) prevents apoptotic death of neuronal
      cells.
AB  - In the present study we tested whether N-acetyl-L-cysteine (LNAC) affects
      apoptotic death of neuronal cells caused by trophic factor deprivation. LNAC, an
      antioxidant, elevates intracellular levels of glutathione. We used serum-deprived
      PC12 cells, neuronally differentiated PC12 cells deprived of serum and NGF, and
      NGF-deprived neonatal sympathetic neurons. In each case LNAC prevents apoptotic
      DNA fragmentation and maintains long-term survival in the absence of other
      trophic support. Unlike NGF, LNAC does not induce or maintain neurite outgrowth
      or somatic hypertrophy. To rule out actions of LNAC metabolic derivatives, we
      assessed N-acetyl-D-cysteine (DNAC). DNAC also prevents death of PC12 cells and
      sympathetic neurons. However, other antioxidants were ineffective in this regard.
      Since it has been hypothesized that trophic factors prevent neuronal death by
      either preventing or coordinating cell cycle progression, we tested whether LNAC
      or DNAC treatment can affect cell cycle. We found that both (but not other
      antioxidants) suppress proliferation and DNA synthesis by PC12 cells and do so at
      concentrations similar to those at which they prevent apoptotic death. Although
      the abilities of LNAC and DNAC to rescue cells from apoptosis triggered by
      trophic factor deprivation could derive from their direct influences on cellular
      responsiveness to oxidative stress, our observations raise the possibility of a
      mechanism involving cell cycle regulation.

PMID- 7722635
TI  - Overexpression of potassium channel RNA: in vivo development rescues neurons from
      suppression of morphological differentiation in vitro.
AB  - Neuronal differentiation often proceeds differently in vitro than it does in
      vivo. Previous work demonstrated that overexpression of potassium channel RNA
      reduces the number of morphologically identifiable neurons that appear in
      cultures prepared from neural plate stage (17-1/2 hr) embryos (Jones and Ribera,
      1994). Here, we report that morphological differentiation of neurons in situ is
      only slightly affected by overexpression of potassium channels. Endogenous
      factors appear to compensate for the effect of channel overexpression. Consistent
      with this view, when cultures are prepared from older neural tube embryos (22-24
      hr), more neurons containing excess potassium channel RNA differentiate
      morphologically in vitro. Exposure in situ to a rapid intracellular calcium
      chelator, but not to tetrodotoxin, omega-conotoxin or a slow calcium chelator,
      prevents the compensation provided by extended development in vivo. Typically,
      RNA overexpression is limited to half of the embryo in order to provide an
      internal control. However, when potassium channel RNA is overexpressed throughout
      the embryo, few neurons differentiate morphologically in vitro, even if cultures
      are prepared from older neural tube embryos. Thus, recovery is possible if a
      minimum of 5 hr of further development in vivo is allowed under conditions in
      which rapid elevations of intracellular calcium are permitted and half of the
      nervous system has normal levels of potassium channel RNA. These results suggest
      that different or additional mechanisms operate in situ than in vitro to promote
      morphological differentiation of neurons.

PMID- 7722636
TI  - Temporal relations of the complex spike activity of Purkinje cell pairs in the
      vestibulocerebellum of rabbits.
AB  - Parasagittal zones in the vestibulocerebellum contain Purkinje cells whose
      complex spike (CS) activity is modulated in response to rotational optokinetic
      stimulation (OKS) about either the vertical axis (VA) or a horizontal axis (HA)
      that is approximately perpendicular to the ipsilateral anterior canal. In
      rabbits, there are two VA zones in both the ventral nodulus and flocculus, two HA
      zones in the flocculus, and one HA zone in the ventral nodulus. We investigated
      the temporal relationship of the CS activity of Purkinje cell pairs in the same
      or different zones of the vestibulocerebellum in ketamine-anesthetized pigmented
      rabbits. A synchronous temporal relationship was defined as the tendency of the
      CS of each Purkinje cell to fire within, at most, 2 msec of one another.
      Generally, neurons in the same zone showed a tendency to exhibit CS synchrony. Of
      82 pairs consisting of two Purkinje cells in the same zone (e.g., two nodulus HA
      cells), 33 were synchronous. In contrast, none of 26 pairs consisting of two
      neurons in functionally different zones (e.g., a VA cell paired with an HA cell),
      showed CS synchrony. Pairs consisting of neurons in spatially separated VA zones
      in the ventral nodulus also showed a tendency to be synchronously related (6/16),
      as did pairs consisting of a nodulus VA cell and a flocculus VA cell (3/14). The
      CS synchrony was higher during OKS in the preferred direction than during
      spontaneous activity. This is the first demonstration that CS synchrony in the
      vestibulocerebellum can be manipulated with a natural sensory stimulus.

PMID- 7722637
TI  - Cellular localization of thrombin receptor mRNA in rat brain: expression by
      mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA.
AB  - Cell culture studies demonstrating that the serine protease thrombin can induce
      neuronal and glial process retraction, glial proliferation, and changes in gene
      expression suggest a role for thrombin in CNS development, plasticity, and
      response to injury. Most cellular responses to thrombin are mediated by
      proteolytic activation of the cloned thrombin receptor (TR), a member of the
      seven transmembrane domain, G-protein-coupled receptor superfamily. As a step
      toward understanding the role of thrombin and its receptor in the CNS, Northern
      blot, in situ hybridization, and immunohistochemical techniques were used to
      analyze the cellular localization of TR mRNA in weanling-age rat brain. TR mRNA
      was broadly distributed across the neuraxis, although expression was very focal
      and often anatomically limited within specific neural structures. The greatest
      hybridization was associated with individual neurons in neocortex,
      cingulate/retrosplenial cortex, and subiculum, subsets of nuclei in hypothalamus,
      thalamus, pretectum, and ventral mesencephalon, and discrete cell layers in the
      hippocampus, cerebellum, and olfactory bulb. Patterns of hybridization included
      neuronal, glial, and ependymal cells, although white matter was uniformly
      negative, as were most cerebrovascular endothelial cells. Expression of TR mRNA
      by astroglia and dopaminergic neurons was confirmed by colocalization with
      immunoreactivity for glial fibrillary acidic protein (GFAP) in hippocampus and
      tyrosine hydroxylase in the substantia nigra. Comparison between TR and
      prothrombin (thrombin's precursor) cRNA hybridization demonstrated distinct but
      overlapping brain distributions of these transcripts, most clearly evident in
      postnatally developing, laminated structures. These results suggest widespread
      utilization of, and multiple physiologic, and possibly pathophysiologic,
      functions for, the thrombin/TR cell signaling system in the CNS.

PMID- 7722638
TI  - The first retinal axons and their microenvironment in zebrafish: cryptic pioneers
      and the pretract.
AB  - The initial development of the optic tract was studied with light and electron
      microscopy in the zebrafish (Danio rerio). Intraocular injections of the
      fluorescent marker, 1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine
      perchlorate (dil), labeled retinal axons and growth cones anterogradely, and
      injections of dil into the optic chiasm labeled retinal ganglion cells
      retrogradely. Labeled tissue was photoconverted and examined electron
      microscopically. The ventronasal retinal quadrant produced the first growth
      cones. They were the first growth cones in the optic stalk. The leading retinal
      growth cones, typically 4-10 in number, advanced alongside the tract of the
      postoptic commissure but rarely sent filopodia into it and never wrapped its
      axons. Instead, the retinal growth cones followed a pretract, a subpial region
      that was morphologically distinct from its surroundings and extended out in front
      of the leading growth cones, presaging the optic tract. Thus, the retinal growth
      cones, previously thought to be followers of preexisting axons, are actually
      cryptic pioneers whose proximity to the earlier axons masks their pioneering
      nature. We suggest that cryptic pioneers and pretracts are probably common
      elsewhere in the nervous system.

PMID- 7722639
TI  - Relative densities of synaptic and extrasynaptic GABAA receptors on cerebellar
      granule cells as determined by a quantitative immunogold method.
AB  - Ion channels gated by the inhibitory neurotransmitter gamma-aminobutyric acid
      (GABA) are thought to be located in synaptic junctions, but they have also been
      found throughout the somatodendritic membrane of neurons independent of synapses.
      To test whether synaptic junctions are enriched in GABAA receptors, and to
      determine the relative densities of synaptic and extrasynaptic receptors, the
      alpha 1 and beta 2/3 subunits of the GABAA receptor were localized on cerebellar
      granule cells using a postembedding immunogold method in cats. Immunoparticle
      density for the alpha 1 and beta 2/3 subunits was approximately 230 and 180 times
      more concentrated, respectively, in the synaptic junction made by GABAergic Golgi
      cell terminals with granule cell dendrites than on the extrasynaptic somatic
      membrane. Quantification of immunoreactivity revealed one synapse population for
      the beta 2/3, but appeared to show two populations for the alpha 1 subunit
      immunoreactivity. The concentration of these subunits on somatic membrane was
      significantly lower than on the extrasynaptic dendritic membrane. Synaptic
      junctions with glutamatergic mossy fiber terminals were immunonegative. The
      results demonstrate that granule cells receiving GABAergic synapses at a
      restricted location on their distal dendrites exhibit a highly compartmentalized
      distribution of GABAA receptor in their plasma membrane.

PMID- 7722640
TI  - ATP causes release of intracellular Ca2+ via the phospholipase C beta/IP3 pathway
      in astrocytes from the dorsal spinal cord.
AB  - Calcium signaling within astrocytes in the CNS may play a role comparable to that
      of electrical signaling within neurons. ATP is a molecule known to produce Ca2+
      responses in astrocytes, and has been implicated as a mediator of intercellular
      Ca2+ signaling in other types of nonexcitable cells. We characterized the signal
      transduction pathway for ATP-evoked Ca2+ responses in cultured astrocytes from
      the dorsal spinal cord. Nearly 100% of these astrocytes respond to
      extracellularly applied ATP, which causes release of Ca2+ from an intracellular
      pool that is sensitive to thapsigargin and insensitive to caffeine. We found that
      intracellular administration of IP3 also caused release of Ca2+ from a
      thapsigargin-sensitive intracellular pool, and that IP3 abolished the response to
      ATP. The ATP-evoked Ca2+ response was blocked by the IP3 receptor antagonist
      heparin, applied intracellularly, but not by N-desulfated heparin, which is not
      an antagonist at these receptors. The Ca2+ response caused by ATP was also
      blocked by a phospholipase C inhibitor, U-73122, but not by its inactive analog,
      U-73343. Increases in [Ca2+]i were elicited by intracellular application of
      activators of heterotrimeric G-proteins, GTP gamma S and AIF4-. On the other
      hand, [Ca2+], was unaffected by a G-protein inhibitor, GDP beta S, but it did
      abolish the Ca2+ response to ATP. Pretreating the cultures with pertussis toxin
      did not affect responses to ATP. Our results indicate that in astrocytes ATP
      evoked release of intracellular Ca2+ is mediated by IP3 produced as a result of
      activating phospholipase C coupled to ATP receptors via a G-protein that is
      insensitive to pertussis toxin. ATP is known to be released under physiological
      and pathological circumstances, and therefore signaling via the PLC-IP3 pathway
      in astrocytes is a potentially important mechanism by which ATP may play a role
      in CNS function.

PMID- 7722641
TI  - Pharmacological dissection of multiple types of Ca2+ channel currents in rat
      cerebellar granule neurons.
AB  - The diversity of Ca2+ channel types in rat cerebellar granule neurons was
      investigated with whole-cell recordings (5 mM external Ba2+). Contributions of
      five different high-voltage-activated Ca2+ channel current components were
      distinguished pharmacologically. Nimodipine-sensitive L-type current and omega
      CTx-GVIA-sensitive N-type current contributed 15 and 20% of the total current,
      respectively. The bulk of the remaining current (46%) was inhibited by omega-Aga
      IVA. The current blocked by this toxin was further subdivided into two
      components, P-type and Q-type, on the basis of differences in their inactivation
      kinetics and sensitivity to omega-Aga-IVA. P-Type current was noninactivating
      during 0.1 sec depolarizations, half-blocked at about 1-3 nM omega-Aga-IVA, and
      contributed approximately 11% of the total current; Q-type current was
      prominently inactivating, half-blocked at approximately 90 nM omega-Aga-IVA, and
      comprised 35% of the total current. Both P- and Q-type currents were potently
      inhibited by the Conus magus toxin omega-CTx-MVIIC. A current component resistant
      to all of the aforementioned blockers (R-type) displayed more rapid inactivation
      than the other components and constituted 19% of the total current. The Q-type
      current, the largest of the current components in the granule neurons, resembles
      currents that can be generated in Xenopus oocytes by expression of cloned alpha
      1A subunits.

PMID- 7722642
TI  - Replacement of hair cells after laser microbeam irradiation in cultured organs of
      corti from embryonic and neonatal mice.
AB  - This study examined the potential for hair cell regeneration in embryonic and
      neonatal mouse organs of Corti maintained in vitro. Small numbers of hair cells
      were killed by laser microbeam irradiation and the subsequent recovery processes
      were monitored by differential interference contrast (DIC) microscopy combined
      with continuous time-lapse video recordings. Replacement hair cells were observed
      to develop in lesion sites in embryonic cochleae and on rare occasions in
      neonatal cochleae. In embryonic cochleae, replacement hair cells did not arise
      through renewed proliferation, but instead developed from preexisting cells that
      changed from their normal developmental fates in response to the loss of adjacent
      hair cells. In cochleae established from neonates, lost hair cells usually were
      not replaced, but 11 apparently regenerated hair cells and a single hair cell
      labeled by 3H-thymidine were observed as rare responses to the creation of hair
      cell lesions in these organs. The results indicate that the organ of Corti can
      replace lost hair cells during embryonic and on rare occasions during early
      neonatal development. The ability of preexisting cells to change their
      developmental fates in response to hair cell death is consistent with the
      hypothesis that during embryonic development hair cells may inhibit neighboring
      cells from specializing as hair cells. In neonatal cultures, the rare occurrence
      of apparently regenerated hair cells indicates that some cells in the
      postembryonic organ of Corti retain response mechanisms that can lead to self
      repair.

PMID- 7722643
TI  - The role of heparin-binding growth-associated molecule (HB-GAM) in the
      postsynaptic induction in cultured muscle cells.
AB  - The heparan sulfate proteoglycan (HSPGs) is a components of the extracellular
      matrix of skeletal muscle that is concentrated at the neuromuscular junction
      (NMJ). Recent studies have suggested that HSPG, together with its bound peptide
      growth factors, plays important roles in autocrine or paracrine types of
      regulation of cell growth and differentiation. Heparin-binding growth-associated
      molecule (HB-GAM; also known as pleiotrophin, or p18) is a newly discovered HSPG
      bound factor that is expressed at high levels in the developing CNS and PNS. In
      this study, we examined the role of this factor in NMJ development by examining
      its relationship to the formation of ACh receptor (AChR) clusters. Using an
      antibody against recombinant rat brain HB-GAM, we found that this protein is
      present prominently on the surface of cultured Xenopus myotomal muscle cells by
      immunocytochemistry. It is associated with HSPGs as evidenced by the fact that
      heparin and heparinase treatment greatly diminished the antibody labeling. HB-GAM
      is concentrated at preexisting AChR hot spots as well as at those induced by
      polystyrene beads. In addition, this molecule is also concentrated at AChR
      clusters induced by spinal cord neurons in nerve-muscle cocultures. To assess its
      function in synaptic induction, we applied recombinant HB-GAM-coated beads to
      cultured muscle cells to effect its focal presentation. Over 70% of these beads
      induced the formation of AChR clusters as shown by fluorescent alpha-bungarotoxin
      labeling. Furthermore, bath application of HB-GAM inhibited the nerve-induced
      formation of AChR clusters. Thus, HB-GAM is an endogenous muscle-derived factor
      that may be a component of the molecular mechanism in postsynaptic induction.

PMID- 7722644
TI  - Maturation-dependent upregulation of growth-promoting molecules in developing
      cortical plate controls thalamic and cortical neurite growth.
AB  - We have tested the hypothesis that maturation-dependent changes in the cortical
      plate affect the spatiotemporal growth patterns of developing thalamocortical and
      corticocortical axonal projections. Given a choice between alternating lanes of
      embryonic (E18-19) and neonatal (P0-1) rat cortical plate membranes, embryonic
      (E18-19) thalamic and cortical neurites prefer to extend on neonatal membranes.
      Thalamic and cortical explants do extend neurites on uniform carpets of E19
      cortical plate membranes, but the outgrowth is consistently greater on uniform
      carpets of P1 cortical plate membranes. These experiments demonstrate a
      maturation-dependent enhancement in the ability of cortical plate to support
      neurite growth from thalamic and cortical explants. In contrast, retinal and
      cerebellar neurites, which do not grow into cortex in vivo, generally grew poorly
      on these membranes, suggesting a degree of specificity to the neurite growth
      response. Immunohistochemical analysis of developing cortex suggests that several
      extracellular matrix (ECM) and cell adhesion molecules are upregulated in
      cortical plate. However, immunocharacterization of membrane carpets for these
      same ECM and cell adhesion molecules suggests that the growth preferences of
      thalamic and cortical neurites in vitro are predominantly influenced by membrane
      anchored, rather than ECM, molecules. Western analysis of E19 and P1 cortical
      plate membranes supports this conclusion, and indicates that the membrane
      anchored cell adhesion molecules L1 and N-CAM are more abundant in the P1
      cortical plate membrane preparation. Experiments in which cortical plate
      membranes were treated to remove molecules sensitive to phosphatidylinositol (PI)
      specific phospholipase C demonstrate that neurite growth promoters present in E19
      cortical plate membranes are predominantly PI linked, whereas those present in P1
      membranes are predominantly non-PI linked. These findings indicate that the
      neurite growth preferences are mediated, at least in part, by an upregulation of
      neurite growth-promoting molecules in developing cortical plate that are not PI
      linked. Taken together, these findings suggest that a maturation-dependent
      upregulation of neurite growth-promoting molecules on cortical plate cells
      controls the invasion of the cortical plate by thalamocortical and
      corticocortical axons.

PMID- 7722645
TI  - Putative pre- and postsynaptic ATP-sensitive potassium channels in the rat
      substantia nigra in vitro.
AB  - Pre- and postsynaptic adenosine 5'-triphosphate-sensitive potassium (ATP-K+)
      currents were studied using whole-cell recordings from substantia nigra zona
      compacta "principal" neurons in midbrain slices. The GABAA and GABAB receptor
      mediated synaptic potentials were unaffected by the ATP-K+ channel inhibitor
      glibenclamide (30 microM) or by the opener diazoxide (500 microM), indicating
      that ATP-K+ channels on GABA-ergic terminals are not active, nor can they be
      activated pharmacologically, under control conditions. However, application of a
      glucose-free solution to reduce intracellular ATP levels caused a reduction of
      the GABAB IPSP in all neurons. This was substantially reversed by the
      sulfonylurea inhibitor tolbutamide (300 microM) in 50% of the neurons tested. The
      reduction of the GABAB IPSP was a presynaptic effect since postsynaptic
      hyperpolarizations induced by the GABAB receptor agonist baclofen (10 microM)
      were unaffected by glucose-free solutions. Diazoxide (500 microM) induced a
      slowly developing hyperpolarization or outward current in 64% of principal
      neurons, which was tolbutamide- (100-300 microM) or glibenclamide- (30 microM)
      sensitive. In contrast, the GABAB receptor agonist baclofen (30 microM) induced a
      rapid hyperpolarization or outward current in all neurons tested that was
      unaffected by tolbutamide (300 microM). Although both the diazoxide-induced
      current and the baclofen-induced current were inhibited by Ba2+ (300 microM), the
      currents elicited by diazoxide and baclofen summated. The reversal potential for
      the diazoxide-induced current was also less negative than that for baclofen,
      which was close to EK. In the presence of intracellular cesium, diazoxide induced
      a tolbutamide-sensitive inward current in a proportion of neurons, indicating
      that it has other actions in addition to activating a potassium current. Our
      results suggest that functional ATP-K+ channels exist both pre- and
      postsynaptically in the SN, where they modulate the activity of principal
      neurons. They are different to the potassium channels activated by the GABAB
      receptor agonist baclofen.

PMID- 7722646
TI  - A novel metabotropic glutamate receptor expressed in the retina and olfactory
      bulb.
AB  - A novel metabotropic glutamate receptor, mGluR8, was identified by screening a
      mouse retina cDNA library. This receptor is most related to mGluR4, mGluR7, and
      mGluR6 (74%, 74%, and 70% identical amino acid residues, respectively). Similar
      to these receptors, stimulation by L-glutamate or L-2-amino-4-phosphonobutyrate
      (L-APB) of Chinese hamster ovary (CHO) cells stably transfected with mGluR8
      result in the inhibition of forskolin-stimulated adenylyl cyclase. In situ
      hybridization studies revealed a strong expression of the mGluR8 gene in the
      olfactory bulb, accessory olfactory bulb, and mammillary body. A weaker
      expression was found in the retina, and in scattered cells in the cortex and
      hindbrain. During development, the distribution of mGluR8 expression was more
      widespread. These results extend the diversity of metabotropic glutamate
      receptors in the CNS. Because at least two APB receptors are expressed in the
      retina, the use of this drug to block selectively the ON pathway needs to be
      reconsidered. The pharmacology and expression of mGluR8 in mitral/tufted cells
      suggest it could be a presynaptic receptor modulating glutamate release by these
      cells at their axon terminals in the entorhinal cortex.

PMID- 7722647
TI  - Differential effects of NGF and BDNF on voltage-gated calcium currents in
      embryonic basal forebrain neurons.
AB  - A number of studies have begun to describe the effects of nerve growth factor
      (NGF) and the closely related brain-derived neurotrophic factor (BDNF) on the
      function of basal forebrain neurons. Little is known, however, about the effects
      of neurotrophins on membrane calcium conductances, which may play a role in
      growth factor signal transduction as well as regulation of neuronal excitability.
      Using the whole-cell patch-clamp technique, we investigated the effects of both
      NGF and BDNF on voltage-gated Ca(2+)-channel currents in cultured embryonic basal
      forebrain neurons. Exposure for 4-6 d to NGF significantly increased both the L
      type and N-type components of the whole-cell current. Conversely, similar
      exposure to BDNF had no effect on Ca(2+)-channel currents. Consequently, one of
      the important effects of NGF may be to enhance calcium entry via voltage
      dependent channels.

PMID- 7722648
TI  - GABAA receptor-mediated inhibition of rat substantia nigra dopaminergic neurons
      by pars reticulata projection neurons.
AB  - Evidence from electrophysiological studies has suggested an inhibitory
      interaction between GABAergic neurons in substantia nigra pars reticulata and
      dopaminergic neurons in pars compacta. However, that this inhibitory interaction
      is due to a projection from pars reticulata to pars compacta has never been
      demonstrated directly, nor has the GABAergic neuron that mediates the interaction
      been identified either electrophysiologically or anatomically. To more closely
      examine interactions between substantia nigra pars reticulata GABA neurons and
      dopaminergic neurons, single unit extracellular recordings were obtained from
      antidromically identified nigrostriatal neurons and their response to antidromic
      activation of nigral GABAergic projection neurons observed. Stimulation of
      superior colliculus or thalamus produced a short latency inhibition of
      dopaminergic neurons. This inhibition was blocked by local application of
      bicuculline but not 2-hydroxysaclofen. Bicuculline caused most dopaminergic
      neurons to fire in a bursty mode, whereas saclofen caused most dopaminergic
      neurons to fire in a pacemaker-like mode. The thalamic-evoked inhibition was not
      affected by kainate lesions of the globus pallidus, but these lesions produced
      effects on firing pattern identical to those produced by saclofen. These data
      demonstrate a short latency inhibition of nigral dopaminergic neurons mediated by
      GABAA receptors that arises from the axon collaterals of pars reticulata
      projection neurons. We propose a model in which the firing pattern of nigral
      dopaminergic neurons in vivo is modulated differentially by disinhibition of
      GABAA inputs arising from pars reticulata projection neuron axon collaterals and
      disinhibition of pallidonigral GABAergic inputs mediated by GABAB receptors.

PMID- 7722649
TI  - Selective increase in T-type calcium conductance of reticular thalamic neurons in
      a rat model of absence epilepsy.
AB  - The properties of voltage-dependent calcium currents were compared in thalamic
      neurons acutely dissociated from a rat model of absence epilepsy, designated as
      Genetic Absence Epilepsy Rat from Strasbourg (GAERS), and from a Nonepileptic
      Control strain (NEC). Two populations of neurons were isolated: thalamocortical
      relay neurons of the nucleus ventrobasalis (VB) and neurons of the nucleus
      reticularis (RT) of the thalamus. Whole-cell patch-clamp analysis demonstrated an
      increase in the amplitude of the calcium (Ca2+) current with a low threshold of
      activation (IT) in RT neurons of GAERS in comparison to that of the seizure-free
      rat strain (-198 +/- 19 pA and -128 +/- 14 pA, respectively), whereas the
      sustained component (IL) was not significantly different. The kinetic properties,
      voltage dependence, and basic pharmacological sensitivity of the Ca2+
      conductances were similar in the two populations of neurons. The amplitude of
      both IT and IL in RT neurons increased after birth, and differences in IT between
      GAERS and NEC attained significance after postnatal day 11. At corresponding
      ages, the Ca2+ currents in VB thalamocortical relay neurons were not altered in
      GAERS in comparison to those in NEC. We conclude that the selective increase in
      IT of RT neurons enhances the probability of recurrent intrathalamic burst
      activity, thereby strengthening the synchronizing mechanisms in thalamocortical
      systems, and, as such, represents a possible primary neuronal dysfunction that
      relates to the pathological increase in synchronization underlying the generation
      of bilateral and synchronous spike and wave discharges (SWDs) in an established
      genetic model of generalized epilepsy.

PMID- 7722650
TI  - The transfer of rats from a familiar to a novel environment prolongs the increase
      of extracellular dopamine efflux induced by CCK8 in the posterior nucleus
      accumbens.
AB  - The effects of cholecystokinin octapeptide (CCK8) on extracellular dopamine (DA)
      and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were
      measured in the nucleus accumbens (N. Acc.). The experiments were carried out
      using in vivo microdialysis in awake rats submitted, or not, to a novel
      environment, the four-hole box. The exploratory behavior of the animals was
      studied concurrently in these boxes and in the elevated plus maze. Without CCK8
      treatment, the transfer of animals from their home cages to the four-hole box
      induced a transient increase in DA efflux and also tended to increase its
      metabolites in the posterior N. Acc. In rats placed in a familiar environment,
      the administration of 25 pmol of CCK8 in this region immediately enhanced DA
      release, with levels rapidly returning to normal at the end of the perfusion. In
      contrast, this treatment produced a longer effect in rats transferred to the four
      hole box, since the DA efflux was still increased 80 min after the removal of
      CCK8. The intra-accumbal administration of CCK8 induced a hypoexploration in the
      four-hole box. Moreover, an anxiogenic-like effect of CCK8 was found in the
      elevated plus maze, only in rats submitted to a novel environment (four-hole
      box). These data show that (1) the postero-accumbens DA neurons can be activated
      by environmental changes and (2) that the intensity of the CCK8 effects on
      extracellular DA levels and on anxiety-like responses seems to depend on the
      activity of these neurons previous to CCK8 treatment. The prolonged DA release
      induced by CCK8 in animals placed in a new situation could correspond to a
      biochemical anticipation preparing them to react when faced by another stimulus.

PMID- 7722651
TI  - Survival of newly postmitotic motoneurons is transiently independent of exogenous
      trophic support.
AB  - We compared the survival requirements of early- and late-born motoneurons from E5
      chicken spinal cord. Density gradient centrifugation followed by immunopanning
      using SC1 antibody allowed us to purify two size classes of motoneuron. Large
      motoneurons retained by 6.8% metrizamide were shown by BrdU labeling in ovo to be
      born on average 1.5 d earlier than the small motoneurons recovered from the
      metrizamide pellet. Large motoneurons were both biochemically and functionally
      more mature: they expressed higher levels of choline acetyltransferase and low
      affinity neurotrophin receptor, and had an acute requirement for trophic support
      from muscle-derived factors. After 24 hr in culture in basal medium, all early
      born motoneurons died, whereas 60% of late-born motoneurons survived. Small
      motoneurons can develop into large motoneurons in ovo, suggesting that they
      represent a general transitional stage in motoneuron development. Our results
      suggest that a defined period elapses between birth of a motoneuron and its
      acquisition of trophic dependence, possibly corresponding to the time required
      for target innervation. This property may have important consequences for the
      timing and regulation of developmental motoneuron death.

PMID- 7722652
TI  - Recordings from slices indicate that octopus cells of the cochlear nucleus detect
      coincident firing of auditory nerve fibers with temporal precision.
AB  - Acoustic information in auditory nerve discharges is integrated in the cochlear
      nuclei, and ascends through several parallel pathways to higher centers. Octopus
      cells of the posteroventral cochlear nucleus form a pathway known to carry
      information in the timing of action potentials. Octopus cells have dendrites
      oriented to receive converging input from many auditory nerve fibers. In all 34
      intracellular recordings from anatomically identified octopus cells in slices,
      shocks to the auditory nerve evoked brief, consistent, graded EPSPs. EPSPs were
      about 1 msec in duration. At all but the lowest shock strengths, the delays
      between shocks and the peaks of resultant EPSPs had SDs of 0.02 msec.
      Polysynaptic excitation, perhaps arising from the axon collaterals of octopus
      cells, was observed. No detectable glycinergic or GABAergic inhibition was evoked
      with shocks. The input resistances were low, around 10 M omega, voltage changes
      were rapid, with time constants of about 1 msec, and action potentials were
      small. The low input resistance resulted in part from a Cs(+)-sensitive
      conductance. In the presence of 10 or 15 mM extracellular Cs+ the time constants
      increased 20-fold in the hyperpolarizing voltage range. As several subthreshold
      inputs were required to produce suprathreshold responses, octopus cells detect
      the coincident firing of auditory nerve fibers. Under physiological conditions
      the low input resistance and resulting short time constant limit the time over
      which temporal summation of excitation from auditory nerve fibers can occur and
      thus provide temporal precision to electrical signaling.

PMID- 7722653
TI  - Antinociception produced by an ascending spino-supraspinal pathway.
AB  - Studies in mice and rats have shown that antinociception produced by intrathecal
      (i.t.) administration of opioids can be partially inhibited by
      intracerebroventricular (i.c.v.) administration of naloxone. In this study we
      tested the hypothesis that this inhibition by i.c.v. naloxone results from
      antagonism of supraspinal endogenous opioid-mediated antinociception produced by
      the action of i.t. opioids on an ascending antinociceptive pathway. In rats
      lightly anesthetized with urethane/alpha-chloralose, i.t. DAMGO, i.t. lidocaine,
      or spinal transection at T5-T6 all attenuated the trigeminal jaw opening reflex
      (JOR) (i.e., were antinociceptive), an effect that was antagonized in each case
      by i.c.v. naloxone. These findings support the suggestion that there exists a
      pathway that ascends from the spinal cord to a supraspinal site that tonically
      inhibits antinociception mediated by supraspinal opioids. When activity in this
      ascending pathway is suppressed (e.g., by i.t. opioids or local anesthetics or by
      spinal cord transection), antinociception mediated by supraspinal opioids is
      disinhibited. To determine the supraspinal site(s) at which endogenous opioid
      dependent antinociception is evoked by i.t. opioids, we microinjected naloxone
      methiodide into several supraspinal sites. Microinjection of naloxone methiodide
      into nucleus accumbens but not into the rostral ventral medulla (RVM) or the
      periaqueductal gray matter (PAG) antagonized the suppression of the JOR produced
      by i.t. DAMGO or lidocaine. The possibility that this ascending pathway may
      represent a source of spinal input to mesolimbic circuitry involved in setting
      the state of sensorimotor reactivity to noxious stimuli is discussed.

PMID- 7722654
TI  - TOPA quinone, a kainate-like agonist and excitotoxin is generated by a
      catecholaminergic cell line.
AB  - The quinone derivative of 2,4,5-trihydroxyphenylalanine (TOPA) is a selective non
      NMDA agonist and excitotoxin. While 3,4-dihydroxyphenylalanine (DOPA)-containing
      physiological solutions have been shown to generate TOPA and TOPA quinone (TOPA
      compounds), there have been no previous reports demonstrating the formation of
      this toxin in biological preparations. Here, using a pheochromocytoma
      catecholaminergic clonal cell line (PC12), we have identified TOPA compounds as
      by-products of catecholamine synthesis. PC12 cells incubated for 45 min with 30
      microM tyrosine as a catecholamine precursor produced 1.0 +/- 0.2 pmol/10(6)
      cells of total TOPA compounds. The formation of these compounds could be enhanced
      nearly twofold when the cells were stimulated with 56 mM KCl. Moreover, the
      addition of a DOPA decarboxylase inhibitor (30 microM NSD-1015) increased the
      formation of TOPA compounds in both the unstimulated and stimulated conditions to
      a maximum of 5.5 +/- 0.7 pmol/10(6) cells after a 45 min incubation. A time
      course analysis revealed that DOPA production above baseline levels coincided
      with the detectable generation of TOPA compounds. Finally, we observed an
      inhibition of TOPA compounds formation by 100 microM reduced glutathione,
      suggesting that these catecholamine products are formed from the extracellular
      autoxidation of DOPA. We propose that TOPA quinone may be an underestimated
      component of catecholamine toxicity that could be partly responsible for the
      demise of neurons in several neurodegenerative disorders, including Parkinson's
      and Huntington's disease. In addition, TOPA quinone may represent the first
      identified selective non-NMDA agonist that may be synthesized in the brain.

PMID- 7722656
TI  - Entorhinal-hippocampal connections and object memory in the rat: acquisition
      versus retention.
AB  - Investigations of the neurobiology of memory using experimental animals have
      modeled many of the characteristic features of amnesia seen in human clinical
      populations. To examine long-term memory, however, animal models of amnesia often
      employ extended measures of acquisition, which stand in contrast to the retention
      measures used with humans. To determine the role of entorhinal-hippocampal
      circuitry on both information acquisition and long-term retention, rats with
      bilateral transections of the angular bundle were trained on three object
      discrimination problems and then retrained two weeks later to measure retention.
      Animals with discrete lesions of the angular bundle, which disrupted perforant
      path connections from the entorhinal cortex to the hippocampus and efferent
      hippocampal-cortical projections, acquired the object discrimination problems
      normally but showed a marked deficit in retention. These findings are important
      because they indicate that the role of entorhinal-hippocampal connections may be
      limited to maintaining some types of information (e.g., single object
      discriminations) for retention. This dissociation, moreover, suggests that
      behavioral paradigms that include a measure of retention may be particularly
      important for characterizing the mnemonic functions of the
      hippocampal/parahippocampal region.

PMID- 7722655
TI  - Presynaptic influence on the time course of fast excitatory synaptic currents in
      cultured hippocampal cells.
AB  - Since the lifetime of synaptically released glutamate is thought to be very
      brief, reflecting diffusion and glutamate uptake, the decay of synaptic currents
      is thought to represent the average elementary lifetime of a receptor channel
      bound only once by transmitter molecules. We show here that the decay of evoked
      non-NMDA synaptic currents can reflect presynaptic factors, in particular, the
      prolonged action of transmitter at postsynaptic receptors under conditions of
      enhanced transmitter release. We show that diffusion, high-affinity glutamate
      uptake, and non-NMDA receptor desensitization are insufficiently rapid to limit
      the decays of evoked synaptic currents to those of miniature synaptic currents in
      microcultures of rat hippocampal cells. Our results are consistent with recent
      studies suggesting that during evoked release, multiple glutamate quanta can
      interact with overlapping postsynaptic receptor domains.

PMID- 7722657
TI  - Excitotoxic activation of the NMDA receptor results in inhibition of
      calcium/calmodulin kinase II activity in cultured hippocampal neurons.
AB  - Neurotoxic effects of excitatory amino acids have been implicated in various
      neurological disorders, and have been utilized for excitotoxic models of delayed
      neuronal cell death. The excitotoxic glutamate-induced, delayed neuronal cell
      death also results in inhibition of calcium/calmodulin-dependent kinase II (CaM
      kinase II). In this report, we characterized the glutamate-induced inhibition of
      CaM kinase II in relation to loss of intracellular calcium regulation and delayed
      neuronal cell death. Glutamate (500 microM for 10 min), but not KCl (50 mM),
      exposure resulted in a significant inhibition of CaM kinase II activity. The
      inhibition of CaM kinase II activity was observed immediately following
      excitotoxic glutamate exposure and present at every time point measured.
      Glutamate-induced inhibition of kinase activity and delayed neuronal cell death
      was dependent upon both the activation of the NMDA glutamate receptor subtype and
      the presence of extracellular calcium. The relationship between inhibition of CaM
      kinase II activity and loss of intracellular calcium regulation was also
      examined. Experimental conditions which resulted in significant neuronal cell
      death and inhibition of CaM kinase II activity also resulted in a long-term loss
      of intracellular calcium regulation. Thus, inhibition of CaM kinase II activity
      occurred under experimental conditions which resulted in loss of neuronal
      viability and loss of neuronal calcium regulation. Since the glutamate-induced
      inhibition of CaM kinase II activity preceded neuronal cell death, the data
      support the hypothesis that inhibition of CaM kinase II activity may play a
      significant role in excitotoxicity-dependent, delayed neuronal cell death.

PMID- 7722658
TI  - Functional analysis of human MT and related visual cortical areas using magnetic
      resonance imaging.
AB  - Using noninvasive functional magnetic resonance imaging (fMRI) technique, we
      analyzed the responses in human area MT with regard to visual motion, color, and
      luminance contrast sensitivity, and retinotopy. As in previous PET studies, we
      found that area MT responded selectively to moving (compared to stationary)
      stimuli. The location of human MT in the present fMRI results is consistent with
      that of MT in earlier PET and anatomical studies. In addition we found that area
      MT has a much higher contrast sensitivity than that in several other areas,
      including primary visual cortex (V1). Functional MRI half-amplitudes in V1 and MT
      occurred at approximately 15% and 1% luminance contrast, respectively. High
      sensitivity to contrast and motion in MT have been closely associated with
      magnocellular stream specialization in nonhuman primates. Human psychophysics
      indicates that visual motion appears to diminish when moving color-varying
      stimuli are equated in luminance. Electrophysiological results from macaque MT
      suggest that the human percept could be due to decreases in firing of area MT
      cells at equiluminance. We show here that fMRI activity in human MT does in fact
      decrease at and near individually measured equiluminance. Tests with
      visuotopically restricted stimuli in each hemifield produced spatial variations
      in fMRI activity consistent with retinotopy in human homologs of macaque areas
      V1, V2, V3, and VP. Such activity in area MT appeared much less retinotopic, as
      in macaque. However, it was possible to measure the interhemispheric spread of
      fMRI activity in human MT (half amplitude activation across the vertical meridian
      = approximately 15 degrees).

PMID- 7722659
TI  - Riding on the information superhighway.

PMID- 7722660
TI  - It's not a drill, it's for real!
AB  - In this article, the authors describe an actual fire on a 40-bed surgical ward in
      a university-affiliated medical center. By the time staff members discovered the
      fire, one patient's bed and room were engulfed in flames and smoke was pouring
      into the hallway. Rapid and appropriate responses of members of the nursing and
      hospital staff prevented injuries to patients and staff members. Eighteen
      patients were evacuated within minutes, and the area of the fire was contained
      quickly. The importance of staff education and preparedness for an internal
      disaster with an emphasis on fire and safety standards is reviewed in this
      article.

PMID- 7722661
TI  - Developing an orientation program for a nurse educator.
AB  - It is ironic that although a major portion of a hospital-based educator's time is
      devoted to planning and teaching new staff members, there is often little or no
      formalized plan for orienting new educators. Nurse educators developed an
      orientation program to address this situation. The orientation program was
      developed, implemented, and evaluated using a model of competency-based
      education, the institution's performance evaluation, and the perceived
      expectations of the educators.

PMID- 7722662
TI  - An approach to presentation skill development of nurses.
AB  - When staff development specialists help nurses gain presentation skills, they
      benefit by increasing the pool of clinically expert nurses who can share
      information and ideas. In this article, the authors describe an approach that
      includes conducting a workshop and providing opportunities for participants to
      make a presentation. Strategies to enhance presentations and reduce fear are
      addressed.

PMID- 7722663
TI  - Knowledge of early intervention in three groups of nurses: implications for
      service and training.
AB  - The mandate for a multidisciplinary approach in early intervention for at-risk
      and developmentally disabled infants and their families is creating new roles and
      opportunities for professionals in a variety of disciplines. The extent to which
      such roles and opportunities will be realized, however, depends on awareness of
      the nature and scope of early intervention efforts. This study was designed to
      examine the awareness of early intervention among nurses as a function of
      professional level. A total group of 64 students, practicing registered nurses,
      and nurse practitioners completed questionnaires assessing (a) their awareness of
      early intervention; (b) their perception of characteristics important in early
      intervention; and (c) assessment of their skill and knowledge in this area.
      Nursing students were significantly less aware than the other two groups of
      nurses who did not differ from each other. Each group differed significantly from
      the other on perceived skills, whereas only the nursing students differed from
      the other two groups in terms of knowledge. The endorsement of family-centered
      intervention did not differ as a function of level of educational preparation. It
      was concluded that nursing education curricula should include information on
      early intervention.

PMID- 7722664
TI  - Nurses as end-user searchers of the literature on CD-ROM.
AB  - As the resource center for nursing information, the staff development department
      is the ideal location for facilitation of end-user searching of the nursing and
      medical literature. The authors report on a project undertaken to encourage
      searching of CD-ROM databases to improve patient care.

PMID- 7722665
TI  - Developing an eclectic model for nursing practice in a community hospital.
AB  - The literature documents the importance of using a conceptual model to explain
      and guide nursing practice (Fawcett, 1989; Riehl-Sisca, 1988; Meleis, 1991).
      However, can a single model describe and guide practice for an entire nursing
      service department? In this article, the author describes and analyzes the
      process of developing an eclectic conceptual nursing practice model as
      experienced by the nursing division of a 250-bed community hospital in the
      midwest.

PMID- 7722666
TI  - Student orientation: a city-wide effort.

PMID- 7722667
TI  - Perspectives on research.

PMID- 7722668
TI  - Computer-assisted instruction using electronic mail.
AB  - A major challenge to nursing staff development departments is how to reach
      individual staff members with new information in a limited period of time.
      Attendance at classroom instruction is not always feasible. The use of electronic
      mail to provide instruction to learners can be an effective teaching strategy.
      Advantages are immediate accessibility to the learner and the opportunity to
      tailor the program to meet specific hospital requirements or individual learning
      needs. Tips on how to develop and send instructional modules through electronic
      mail are included in this article.

PMID- 7722669
TI  - The Nursing Research Journal Club: an ongoing program to promote nursing research
      in a community hospital.

PMID- 7722670
TI  - Assessing and improving nursing feeding skills of geropsychiatric hospital staff
      members, especially psychiatric aides.

PMID- 7722671
TI  - Evaluation of preceptor competence and cost in an acute care hospital.

PMID- 7722672
TI  - Contact hour feature to be reinstated?

PMID- 7722673
TI  - Preceptor development. An opportunity to stimulate critical thinking.
AB  - In this article, the authors describe a preceptor development program with
      several unique features. The program provides preceptors with strategies to
      promote critical thinking and has expanded content on feedback and evaluation
      processes. Ongoing professional development is continued through follow-up
      seminars. These seminars provided preceptors with an opportunity to share their
      experiences, which led to identification of important issues for further
      exploration. For example, preceptors need assistance developing teaching
      strategies to meet the needs of the middle-aged new graduate nurse.

PMID- 7722674
TI  - Eliminating friendly fire. Successful nursing documentation strategies.
AB  - Often, an institution's documentation policies, procedures, and records become
      frustrating instruments of torture rather than helpful resources for the nurses
      who must use them. In this article, the authors highlight several of the
      strategies used by one nursing service department to eliminate barriers to
      adequate documentation.

PMID- 7722675
TI  - Shriners' challenge. A game format for a mandatory inservice program.
AB  - Traditional methods of reviewing required material on Infection Control and Risk
      Management are boring, time-consuming, and costly. Traditionally, several annual
      presentations each year review already known material. In this article, the
      author describes an innovative approach--a game show format--that involves the
      active participation of every staff member. Each employee is required to attend
      only once a year, resulting in significant savings to the hospital.

PMID- 7722676
TI  - Meeting the challenge of mandatory continuing education.
AB  - A state's decision to institute mandatory continuing education has ramifications
      for individuals involved in staff development and inservice education. In
      collaboration with the University of Delaware College of Nursing along with the
      Medical Center of Delaware, the Delaware Nurses' Association in 1990 assessed the
      continuing education needs and interests of a convenience sample of 547
      registered nurse Delaware Nurses' Association members. Analysis of the data
      revealed a variety of interests within practice, education, administration, and
      research. The most preferred method of acquiring continuing education was
      attendance at a live conference, with part-day morning programs favored by a
      majority of the sample. Consequently, staff development and inservice educators
      are challenged with meeting the needs of the organization and the individual
      employee in an era of diminishing resources.

PMID- 7722677
TI  - Understanding research articles. A pilot study of critical reading of research
      publications.
AB  - Developing nurses' ability to understand and evaluate research articles for
      potential application to practice is a challenge for staff development
      professionals. Articles are laden with difficult terminology and may seem too
      difficult. Yet valuable insights for improving patient care rest within the
      literature. In this article, the authors describe an instructional tool, designed
      in the federal nursing sector, called Critical Reading of Research Publications
      (CRRP). The CRRP is an independent study program that helps small groups of
      nurses increase research understanding while reading relevant articles of
      clinical interest.

PMID- 7722678
TI  - Dietary canola oil modifies myocardial fatty acids and inhibits cardiac
      arrhythmias in rats.
AB  - Previous research showed that dietary fish oil was potently antiarrhythmic in
      rats but olive oil was not. This study was designed to test the hypothesis that
      canola oil, another major dietary source of oleic acid additionally containing
      the (n-3) polyunsaturated fatty acid alpha-linolenic acid [18:3(n-3)], can reduce
      vulnerability to cardiac arrhythmia in rats. Rats were randomly assigned to one
      of four experimental diet groups for 12 wk. The fat source in the diets was 12%
      olive (63% oleic acid), canola (55% oleic, 8% alpha-linolenic acid), soybean [50%
      linoleic 18:2(n-6), 7% alpha-linolenic acid] or sunflower seed oil (64% linoleic
      acid). Arrhythmias were induced by coronary artery occlusion and reperfusion.
      Incidence of ventricular fibrillation, mortality and arrhythmia score during
      reperfusion were significantly lower in rats fed the diet containing canola oil
      than in those fed the olive oil diet. No difference in the severity of
      arrhythmias was seen in groups fed diets containing soybean or sunflower seed
      oils. Analysis of myocardial phospholipid fatty acids showed that consumption of
      canola oil decreased the ratio of (n-6)/(n-3) polyunsaturated fatty acids
      relative to the other diets, as does dietary fish oil. These results suggest that
      regular substitution of canola oil for other dietary lipid sources may assist in
      reducing the likelihood of a transient ischemic event leading to life-threatening
      cardiac arrhythmias, but the effectiveness of alpha-linolenic acid is reduced by
      high levels of linoleic acid.

PMID- 7722679
TI  - Fermentable fibers or oligosaccharides reduce urinary nitrogen excretion by
      increasing urea disposal in the rat cecum.
AB  - The availability of fermentable carbohydrates could influence the digestive
      degradation and disposal of blood urea. The effects of a poorly fermented
      cellulosic oat fiber, a soluble fermentable fiber (gum arabic) or one of two
      oligosaccharides (fructooligosaccharide or xylooligosaccharide) on nitrogen
      excretion were compared with a wheat starch-based control diet in male Wistar
      rats. The fibers and oligosaccharides were added to the semipurified diets at 7.5
      g/100 g in place of wheat starch. The diets contained 13 g casein/100 g. Oat
      fiber did not cause an enlargement of the cecum. In contrast, gum arabic and the
      oligosaccharides elicited a 35-60% enlargement of the cecal wall and a 2 to 2.6
      fold mean increase in the cecal pool of short chain fatty acids. Compared with
      rats fed the oat fiber-based diet, urea flux from blood to cecum was nearly 50%
      greater and more than 120% greater in those fed the gum arabic and
      oligosaccharide diets, respectively. In those groups, net nitrogen retention in
      the cecum more than doubled (nitrogen retention was calculated as the difference
      between net urea nitrogen flux into the cecum and ammonia nitrogen reabsorption).
      As a percentage of total excreted nitrogen, fecal nitrogen was 20% in the oat
      fiber group and 27-29% in the gum arabic and oligosaccharide groups, compared
      with only 10% in fiber-free controls. Results indicate that under these dietary
      conditions, the addition of oligosaccharides to the diet induced a 20 to 30%
      decrease in blood urea and renal and renal nitrogen excretion relative to the
      control, indicating a potential for oligosaccharide diet therapy in chronic renal
      disease.

PMID- 7722680
TI  - Protein-energy malnutrition during gestation and lactation in rats affects growth
      rate, brain development and essential fatty acid metabolism.
AB  - The influence of feeding a low protein diet to rat dams during gestation and
      lactation on lipid metabolism in pups was studied. Wistar rats were fed 5, 10, 15
      and 25% dietary protein during gestation and lactation. Pup growth was monitored
      until weaning, and brain weight, protein concentration, proteolipid concentration
      and total lipid phosphorus concentration of brain were analyzed. The levels of
      fatty acids in dam milk as well as in pup liver phospholipids and brain
      prosphatidylcholine and phosphatidylethanolamine were determined. The progressive
      deprivation of maternal dietary protein produced a reduction in the total
      saturated fatty acid concentration of dam milk and an increment in the
      concentration of nonmetabolized linoleic acid. Pup body and brain weights as well
      as proteolipid, protein and total lipid phosphorus concentrations in brain were
      reduced in proportion to the degree of dietary protein deficiency. The
      products:precursor ratio of (n-6) fatty acids in liver phospholipids revealed an
      impairment in the elongation-desaturation pathway due to maternal protein
      deficiency. Both (n-6) and (n-3) polyunsaturated fatty acids within brain
      phosphatidylethanolamine were decreased by reduced maternal dietary protein
      intake, whereas only the linoleic acid-derived products were similarly affected
      in the corresponding phosphatidylcholine fraction. These results demonstrate the
      widespread and profound deleterious effects of low protein levels of maternal
      diet on the growth rate, brain development and fatty acid metabolism in rat pups.

PMID- 7722681
TI  - Dairy proteins protect against dimethylhydrazine-induced intestinal cancers in
      rats.
AB  - The impact of different dietary protein sources (whey, casein, soybean, red meat)
      on the incidence, burden and mass index of intestinal tumors induced by
      dimethylhydrazine in male Sprague-Dawley rats was assessed. A purified diet
      (based on AIN-76A) with a fat concentration of 20 g/100 g and other proteins
      substituted for casein (20 g/100 g) was used. Whey and casein diets were more
      protective against the development of intestinal tumors than were the red meat or
      soybean diets, as evidenced by a reduced incidence of rats affected (P = 0.15),
      fewer tumors per treatment group (burden, P < 0.005), and a reduced pooled area
      of tumors (tumor mass index) that formed (P = 0.39). Intracellular concentration
      of glutathione, an antioxidant and anticarcinogenic tripeptide, measured in
      liver, was greatest in whey protein- and casein-fed rats and lowest in soybean
      fed animals (P < 0.001). For other tissues (spleen, colon, tumor) the differences
      were not significant, although the whey-fed animals had the highest
      concentrations of glutathione (P = 0.8). Whey is a source of precursors (cysteine
      rich proteins) for glutathione synthesis and may be important in providing
      protection to the host by stimulating glutathione synthesis. A positive
      correlation was observed between mean fecal fat concentrations for rats in each
      treatment group and large intestinal tumor burden (r2 = 0.898, P = 0.05). Fecal
      fat could be involved in aiding initiation and/or promotion of carcinogenesis.
      Whatever the mechanism(s), dairy proteins, and whey proteins in particular, offer
      considerable protection to the host against dimethylhydrazine-induced tumors
      relative to the other protein sources examined.

PMID- 7722682
TI  - A mixture of nucleosides and nucleotides increases bone marrow cell and
      peripheral neutrophil number in mice infected with methicillin-resistant
      Staphylococcus aureus.
AB  - We studied the effects of a mixture of nucleosides and nucleotides on the
      peripheral neutrophil number and the proliferation of bone marrow cells in mice
      challenged with methicillin-resistant Staphylococcus aureus. BALB/c mice were fed
      a nucleotide-free 20% casein diet (control) or this diet supplemented with
      nucleosides and nucleotides orally (Expt. 1) or intraperitoneally (Expt. 2 and
      3). On d 10, the mice were challenged intravenously with methicillin-resistant S.
      aureus (6.7 x 10(12) colony forming units/L). In Expt. 1 and 2, numbers of total
      and differential counts of blood leucocytes were counted on d 0 (before), 1, 3
      and 5 after the infection. In Expt. 3, 30 min before killing, bromodeoxyuridine
      (20 mg/kg), an analogue of thymidine, was administered intraperitoneally and its
      incorporation in the DNA synthetic phase of bone marrow cells was determined at 0
      h (before), 3, 6 and 24 h after the infection. Mice fed the supplemented diet had
      higher (P < 0.05) leucocyte and neutrophil numbers on d 0 compared with the
      control group. The neutrophil numbers tended to be greater in the supplemented
      group at 1, 3 and 5 d after the infection. Intraperitoneal administration of
      nucleosides and nucleotides increased (P < 0.05) neutrophil numbers before and
      after the infection. Twenty-four h after the infection, incorporation of
      bromodeoxyuridine into the DNA synthetic phase of bone marrow cells in the group
      administered nucleosides and nucleotides was higher (P < 0.05) than in the
      control group. We conclude that, following methicillin-resistant S. aureus
      injection, intraperitoneal administration of a nucleoside-nucleotide mixture may
      stimulate bone marrow cell proliferation and increase the peripheral blood
      neutrophil numbers. Oral administration may elicit weaker effects.

PMID- 7722683
TI  - Zinc deficiency causes oxidative damage to proteins, lipids and DNA in rat
      testes.
AB  - To investigate the effects of zinc deficiency on oxidative damage to testes
      proteins, lipids and DNA, weanling male rats were allowed free access to low (0.5
      microgram Zn/g) or adequate (25 micrograms Zn/g) zinc diets for 14 d. A third
      group was restricted intake of the adequate Zn diet to the amount consumed by the
      low Zn diet-fed group. Compared with ad libitum-fed controls, testes from rats
      fed the low zinc diet had lower glutamine synthetase activity, lower Fe(2+)
      stimulated 2-thiobarbituric acid-reactive substances (TBARS) production, higher
      protein carbonyl concentrations (P < 0.05), and higher 8-oxo-2'-deoxyguanosine
      levels (P = 0.06). Glutamine synthetase activity in testes of the food-restricted
      controls was between the values for the ad libitum controls and zinc-deficient
      animals. Protein carbonyls were higher in the restricted controls compared with
      the ad libitum controls, whereas stimulated TBARS production was lower (P <
      0.05). Levels of 8-oxo-2'-deoxyguanosine were lower in testes DNA of the
      restricted controls than in the zinc-deficient group (P < 0.05). Testes iron
      concentrations were higher in the zinc-deficient and restricted control rats than
      in ad libitum controls (P < 0.05). The oxidative damage observed may have
      occurred as a consequence of increased reactive oxygen species generation
      secondary to tissue iron accumulation and/or reductions in zinc-dependent
      antioxidant processes.

PMID- 7722684
TI  - Dietary magnesium supplementation modifies blood pressure and cardiovascular
      function in mineralocorticoid-salt hypertensive rats but not in normotensive
      rats.
AB  - The purpose of this study was to determine the effect of dietary magnesium
      supplementation on blood pressure and cardiovascular function of Sprague-Dawley
      normotensive and mineralocorticoid-salt (DOCA-salt) hypertensive rats. The rats
      were pair-fed for 5 wk a purified diet containing either a normal or magnesium
      supplemented diet (1.5 or 10 g/kg diet). Magnesium supplementation significantly
      lowered blood pressure levels in hypertensive rats, but not in normotensive rats.
      Heart rate was not affected in either group. The blood pressure-lowering effect
      of magnesium supplementation in DOCA-salt hypertensive rats was associated with a
      lower in vivo cardiovascular reactivity to norepinephrine and angiotensin II.
      Norepinephrine reactivity in isolated aortae from DOCA-salt hypertensive rats was
      not modified by magnesium supplementation. However, endothelium-dependent
      relaxation to acetylcholine was improved and could be related to the release of
      endothelial relaxant factors. Magnesium supplementation did not affect cardiac
      hemodynamics in isolated heart from either normotensive or DOCA-salt hypertensive
      rats. Furthermore, no protective effects upon myocardial ischemia and ventricular
      arrhythmias were demonstrated. These findings suggest that the lowering effect of
      magnesium supplementation on blood pressure in hypertensive rats may be related
      to a vascular effect of magnesium that reduces vascular tone. Mechanisms related
      to the pathophysiological development of mineralocorticoid-salt hypertension may
      be involved.

PMID- 7722685
TI  - Abomasal nitrogen flow affects the relationship between dietary nitrogen and
      insulin-like growth factor-I in growing lambs.
AB  - Twelve abomasally cannulated wether lambs were fed isocaloric diets containing 9,
      12 or 15% crude protein to determine insulin-like growth factor-I (IGF-I)
      responses to altered abomasal nitrogen flow and nitrogen status. Lambs were
      offered 1100 g/d of their respective diets. Voluntary feed consumption was not
      affected by nitrogen intake. Ruminal and total tract digestibilities of dry
      matter, organic matter and nitrogen increased linearly (P < 0.05) with increased
      dietary nitrogen. Abomasal flows of total, bacterial and rumen escape nitrogen
      increased (linear, P < 0.01), whereas dry matter and organic matter flows
      decreased (linear, P < 0.01). Total amino acid flow was greater (linear, P <
      0.01) in lambs fed additional nitrogen due to increased (linear, P < 0.01) flows
      of essential and nonessential amino acids. Nitrogen retention and blood urea
      nitrogen increased linearly (P < 0.01). Serum IGF-I concentrations and relative
      hybridization intensity of hepatic IGF-I mRNA increased (linear, P < 0.05) as
      lambs consumed more nitrogen. Serum IGF-I and hepatic IGF-I mRNA were correlated
      positively (P < 0.05) with nitrogen intake and abomasal flows of nitrogen and
      various amino acids. These data provide evidence of a relationship between
      abomasal amino acid flow, as influenced by nitrogen intake, and hepatic gene
      expression and serum concentrations of IGF-I in growing lambs.

PMID- 7722686
TI  - L-2-oxothiazolidine-4-carboxylate, a cysteine precursor, stimulates growth and
      normalizes tissue glutathione concentrations in rats fed a sulfur amino acid
      deficient diet.
AB  - The efficiency of L-2-oxothiazolidine-4-carboxylate, a cysteine precursor, in
      stimulating glutathione synthesis and growth was evaluated in growing rats.
      Animals were fed a sulfur amino acid-deficient diet (0.25% L-methionine and no
      cysteine) supplemented with L-2-oxothiazolidine-4-carboxylate (0.35%) for 3 wk
      and compared with age-matched animals receiving the sulfur amino acid-deficient
      diet alone. Rats fed the sulfur amino acid-deficient diet had lower glutathione
      concentrations in bronchoalveolar lining fluid, lung, lymphocytes, and liver than
      rats fed a sulfur amino acid-deficient diet supplemented with L-2-oxothiazolidine
      4-carboxylate. Rats fed the supplemented diet had normal tissue and
      bronchoalveolar lining fluid glutathione levels. Central venous plasma
      glutathione concentrations, mostly reflecting liver excretion, were less affected
      by L-2-oxothiazolidine-4-carboxylate supplementation. Rats fed L-2
      oxothiazolidine-4-carboxylate supplementation had normal weight gain compared
      with a much lower weight gain in animals fed the sulfur amino acid-deficient diet
      alone. Thus, L-2-oxothiazolidine-4-carboxylate increased tissue glutathione
      concentrations and stimulated growth in rats. The lung glutathione status of the
      rats was reflected by glutathione concentrations in lymphocytes and the
      bronchoalveolar lining fluid, but not by the central venous plasma glutathione
      concentrations.

PMID- 7722687
TI  - Gender, dietary copper and carbohydrate source influence cardiac collagen and
      lysyl oxidase in weanling rats.
AB  - The present investigation was conducted to determine the effects of consumption
      of diets containing fructose or cornstarch on cardiac collagen metabolism in
      weanling male and female rats fed copper-deficient or copper-adequate diets for 5
      wk. Although both male and female rats that consumed the copper-deficient diet
      containing fructose were similarly copper deficient, only the males showed severe
      cardiac pathologies and two died prematurely due to heart-related abnormalities.
      These pathologies were accompanied by a significant reduction of cardiac lysyl
      oxidase activity and elevated soluble and total cardiac collagen concentrations
      compared with rats fed copper-adequate diets. These abnormalities were less
      severe in copper-deficient rats fed cornstarch. The data show that the activity
      of the copper-containing enzyme lysyl oxidase is affected by both dietary
      carbohydrate and gender. The pathologies of heart tissue could be the result of
      abnormal crosslinking of collagen induced by the combination of copper
      deficiency, fructose feeding and the sex of the rats.

PMID- 7722688
TI  - Growth and plasma triiodothyronine concentrations are modified by selenium
      deficiency and repletion in second-generation selenium-deficient rats.
AB  - Classical glutathione peroxidase (GPX) is a useful Se-dependent parameter for
      determining Se status, but loss of GPX activity alone cannot explain the full
      effects of Se deficiency. The recent identification of type I thyroxine 5'
      deiodinase as a Se-dependent enzyme provides a new potentially critical role for
      Se. To develop a model of impaired growth due to Se deficiency, second generation
      deficient weanling rats were fed a Se-deficient amino acid diet with adequate
      vitamin E and methionine. Initial growth rates of deficient males and females
      were 53 and 63%, respectively, of rats fed 0.1 micrograms Se/g diet. In short
      term experiments with deficient males, liver Se and GPX activity were reduced
      99%, liver glutathione-s-transferase activity was increased 114%, plasma
      thyroxine concentrations were increased 67%, plasma triiodothyronine was
      decreased 23% and the plasma triiodothyronine:thyroxine ratio was decreased 55%,
      compared with rats fed 0.2 micrograms Se/g diet. When deficient rats were
      injected on d 14 with 0, 1, 5 or 10 micrograms Se/100 g, rats grew 4.45, 7.62,
      7.17 and 9.05 g/d, respectively, over the next 7 d. Injection with 10 micrograms
      Se/100 g restored plasma thyroxine and triiodothyronine concentrations 7 d later.
      Rats injected with 1 microgram Se/100 g rat had significantly altered plasma
      thyroxine and triiodothyronine concentrations 1 but not 7 d after injection.
      Infusion of Se-deficient rats with 438 ng triiodothyronine/d for 7 d restored
      plasma triiodothyronine concentrations but did not increase growth rate compared
      with rats infused with saline. This model produced a significant growth
      depression that was significantly reversed by as little as 1 microgram Se/100 g
      rat, but not by triiodothyronine infusion, suggesting that other Se-dependent
      roles in addition to 5'-deiodinase and GPX are necessary for adequate growth.

PMID- 7722689
TI  - The impaired growth induced by zinc deficiency in rats is associated with
      decreased expression of the hepatic insulin-like growth factor I and growth
      hormone receptor genes.
AB  - This study was conducted to determine whether dietary zinc status affects the
      expression of the insulin-like growth factor I and growth hormone receptor/growth
      hormone binding protein genes in the liver of growing rats. Weanling male Sprague
      Dawley rats were randomly allotted to zinc-deficient, pair-fed or ad libitum-fed
      dietary treatments and fed diets containing no added zinc for 14 d. Zinc acetate
      was added to the deionized, distilled water (30 mg/L) provided to pair-fed and ad
      libitum-fed rats. As expected, zinc deficiency significantly reduced growth rate
      by 60% and was associated with a significantly lower serum insulin-like growth
      factor I concentration (46 and 67% lower than pair-fed and ad libitum-fed rats,
      respectively). The reduction in serum insulin-like growth factor I concentration
      was associated with a decrease in insulin-like growth factor I gene expression.
      The abundance of the 7.5-kb insulin-like growth factor I mRNA transcript in zinc
      deficient and pair-fed rats was 14 and 31% that of the ad libitum-fed rats. The
      0.8-1.2-kb insulin-like growth factor I transcript also was significantly lower
      in the zinc-deficient and pair-fed rats. In contrast, the abundance of the 1.8-kb
      insulin-like growth factor I transcript was unaffected by zinc deficiency. The
      growth hormone receptor mRNA levels of zinc-deficient and pair-fed rats were 17
      and 50% and their growth hormone binding protein mRNA levels were 46 and 65%
      those of the ad libitum-fed rats. In summary, zinc deficiency markedly decreases
      expression of the insulin-like growth factor I and growth hormone receptor
      genes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722690
TI  - Twenty-four-hour recall overestimates the dietary intake of malnourished
      children.
AB  - Food intake and morbidity are the two main proximal determinants of childhood
      malnutrition. Intake is usually assessed through the 24-h recall method. Few
      studies, however, have evaluated the accuracy of this method; in particular, it
      is not known whether accuracy varies according to the child's nutritional status.
      The intake of 50 children (< 2 y old), of whom 25 were underweight (weight-for
      age more than 2 SD below the National Center for Health Statistics reference), as
      evaluated through weighing of all foods (gold standard) and through recall. The
      overall intakes of energy, fat and protein were significantly greater according
      to the recall method than by weighing. The trend towards overestimation was more
      marked for malnourished children than for well-nourished children. The
      possibility of such bias should be taken into account in future studies.

PMID- 7722691
TI  - Growth improvements in children above 3 years of age: the Cali Study.
AB  - The Cali Study involved the random assignment of 301 malnourished children to be
      exposed to one (CT1, n = 113), two (CT2, n = 64), three (CT3, n = 62) or four
      (CT4, n = 62) 9-mo periods of a multifocal day care-based intervention (i.e.,
      education, health and nutrition). The ages at which the intervention was
      initiated for Groups CT4, CT3, CT2 and CT1 were 3.5, 4.2, 5.2 and 6.1 y,
      respectively. After the experimental phase, children were followed up in
      elementary school until they were 10.4 y old. Our secondary data analyses show
      that children who were exposed at an earlier age and for a longer period of time
      showed the highest degree (P < or = 0.05) of improvement in weight and linear
      growth during the pre-school period. These improvements in physical growth could
      no longer be detected 3 y after the termination of the intervention.

PMID- 7722692
TI  - School breakfast improves verbal fluency in undernourished Jamaican children.
AB  - School feeding programs exist in many countries, but few have been properly
      evaluated. In this study, the short-term effects of breakfast on children's
      cognitive functions were examined. The subjects were 97 undernourished (weight
      for-age < or = -1 SD of reference) and 100 adequately nourished (weight-for-age >
      -1 SD) children in four primary schools in rural Jamaica. The children were
      randomly assigned to a group provided with breakfast or a group given a quarter
      of an orange as a placebo, and then given a battery of four cognitive function
      tests. After a few weeks the treatments were reversed and the tests repeated.
      Undernourished children's performance improved significantly on a test of verbal
      fluency when they received breakfast, whereas that of the adequately nourished
      children did not change (breakfast x group interaction, P < 0.05). There were no
      other effects of breakfast on test scores. The findings extend those of a
      previous Jamaican study conducted under more controlled conditions, and support
      the targeting of school meals to undernourished children.

PMID- 7722693
TI  - Patients with anorexia nervosa demonstrate deficiencies of selected essential
      fatty acids, compensatory changes in nonessential fatty acids and decreased
      fluidity of plasma lipids.
AB  - The objective of this study was to assess the essential fatty acid status of
      patients with anorexia nervosa. Blood was collected from eight fasting female
      anorexia nervosa patients with a mean of 81% ideal body weight. Fatty acid
      composition of phospholipids, nonesterified fatty acids, triglycerides and
      cholesteryl esters of plasma were determined by capillary gas chromatography to
      indicate polyunsaturated fatty acids status compared with 19 healthy female
      adults < 25 y old. Subjects with anorexia nervosa showed polyunsaturated fatty
      acid deficiencies in plasma phospholipids different from simple nutritional
      essential fatty acid deficiency or chronic malnutrition. The phospholipid profile
      showed significantly lower (n-6) and (n-3) elongation and desaturation products,
      and elevated short-chain saturated, short-chain monounsaturated, branched-chain
      and odd-chain fatty acids. These elevations indicate enhancement of biosynthesis
      of alternative fatty acids that only partially compensated for the loss of
      polyunsaturated fatty acids in providing membrane "fluidity." Calculated mean
      melting point of the fatty acids of phospholipids in patients with anorexia
      nervosa was elevated 7.7 degrees C above normal values. These results demonstrate
      that patients with anorexia nervosa have deficiencies of selected essential fatty
      acids, compensatory changes in nonessential fatty acids and decreased fluidity of
      plasma lipids.

PMID- 7722694
TI  - Tumor necrosis factor-alpha alters maternal and embryonic zinc metabolism and is
      developmentally toxic in mice.
AB  - We tested the hypothesis that tumor necrosis factor-alpha (TNF-alpha) would be
      teratogenic in mice due in part to its effects on zinc metabolism. In Experiment
      1, nonpregnant mice were injected with a single dose of TNF-alpha (40,000 U) or
      PBS and then received a 65Zn-labeled meal. Mice killed 10 h after TNF-alpha
      treatment had high liver 65Zn and low plasma 65Zn, compared with controls. In
      Experiment 2, gestation day 8 (GD 8) mice were injected with PBS or TNF-alpha and
      then received a 65Zn-labeled meal. Dams killed 10 h after TNF-alpha treatment had
      higher liver and kidney 65Zn and lower plasma and embryonic 65Zn accumulation
      than controls. In Experiment 3, TNF-alpha dosing from GD 7-12 was associated with
      high maternal liver Zn and metallothionein concentrations on GD 13 and a high
      frequency of exencephaly on GD 18. In Experiment 4, dams fed diets containing
      4.5, 12.5 or 50.0 micrograms Zn/g were given PBS or TNF-alpha on GD 7-12. Gross
      fetal defects were not observed in the PBS-treated litters evaluated on GD 18. In
      contrast, TNF-alpha-treated litters were characterized by multiple defects, with
      the incidence and severity being highest in the low Zn diet group. In Experiment
      5, embryos cultured in serum from TNF-alpha-treated animals exhibited a high
      frequency of defects; the developmental toxicity of this serum was ameliorated
      when it was supplemented with Zn. Thus, the developmental toxicity of TNF-alpha
      is due in part to its influence on Zn metabolism.

PMID- 7722695
TI  - Diet-induced thermogenesis is lower in rats fed a lard diet than in those fed a
      high oleic acid safflower oil diet, a safflower oil diet or a linseed oil diet.
AB  - The objectives of the present study were to examine the effects of dietary fats
      differing in fatty acid composition on diet-induced thermogenesis, sympathetic
      activity in brown adipose tissue and body fat accumulation in rats. Rats were
      meal-fed for 12 wk an isoenergetic diet based on lard, high oleic acid safflower
      oil, safflower oil or linseed oil, and norepinephrine turnover rates in brown
      adipose tissue were then estimated. Whole-body oxygen consumption after the meal
      indicated that diet-induced thermogenesis was significantly lower in rats fed the
      lard diet than in those fed the other diets. The norepinephrine turnover rate in
      the interscapular brown adipose tissue was also significantly lower in the lard
      diet group than in the other diet groups. The carcass fat content was
      significantly higher in the lard diet group than in the other diet groups,
      whereas the abdominal adipose tissue weights were the same in all diet groups.
      These results suggest that the intake of animal fats rich in saturated fatty
      acids, compared with the intake of vegetable oils rich in monounsaturated or
      polyunsaturated fatty acids, decreases diet-induced thermogenesis by a decline of
      sympathetic activity in brown adipose tissue, resulting in the promotion of body
      fat accumulation.

PMID- 7722696
TI  - Pyridoxine-5'-beta-D-glucoside influences the short-term metabolic utilization of
      pyridoxine in rats.
AB  - This study was conducted to characterize the initial time course of the apparent
      competitive effect of pyridoxine-5'-beta-D-glucoside against co-ingested
      pyridoxine. Two groups of rats were administered a single oral dose of 100 nmol
      of [14C]pyridoxine along with either 0 or 20 nmol of unlabeled pyridoxine-5'-beta
      D-glucoside. At 6, 12, 24 and 48 h post-dose, the distribution of labeled vitamin
      B-6 metabolites in blood, tissues and urine was determined. Urinary [14C]4
      pyridoxic acid comprised a significantly greater percentage of excreted 14C in
      the control group, with the greatest difference at 12 h post-dose. Pyridoxine-5'
      beta-D-glucoside (10-15 nmol) was excreted mainly in unchanged form within 6 h.
      Rats that received pyridoxine-5'-beta-D-glucoside retained less 14C in liver,
      with a maximal difference between groups at 6-12 h post-dose. The relative
      concentrations of hepatic [14C]pyridoxal 5'-phosphate and [14C]pyridoxamine 5'
      phosphate in the treatment group were greater than in the control group at
      approximately 12 h post-dose. At 48 h post-dose, there was no difference in the
      distribution of any vitamin B-6 metabolite except pyridoxal 5'-phosphate in the
      two groups. These results confirm that a small, nutritionally relevant dose of
      pyridoxine-5'-beta-D-glucoside influences the utilization of pyridoxine and
      indicate that this is a short-term, transient effect.

PMID- 7722697
TI  - Rats fed a low protein diet supplemented with sulfur amino acids have increased
      cysteine dioxygenase activity and increased taurine production in hepatocytes.
AB  - The metabolism of cysteine and cysteinesulfinate and the activities of key
      enzymes in cysteine catabolic pathways were investigated in hepatocytes isolated
      from rats fed a basal (100 g casein/kg) diet or the diet supplemented with L
      methionine (3 or 10 g/kg diet) or the sulfur equivalent as L-cystine (2.4 or 8
      g/kg diet). Cysteine dioxygenase activity was higher in hepatocytes from rats fed
      diets with the higher level of sulfur amino acid supplementation, and the higher
      enzyme activity was paralleled by a greater total catabolite production (taurine
      + sulfate) from cysteine. Taurine production as a percentage of total cysteine
      catabolism was significantly greater in hepatocytes from rats fed the diet with
      excess methionine or cystine (basal, 22%; excess methionine, 61%, excess cystine,
      49%). Glutathione production was markedly lower in hepatocytes from rats fed
      excess sulfur amino acids such that total cysteine utilization was similar for
      all dietary treatments. Cysteinesulfinate decarboxylase activity and catabolism
      of cysteinesulfinate by hepatocytes were unaffected by the dietary
      supplementations. Results are in contrast to previous studies in which increased
      dietary protein resulted in decreased cysteinesulfinate decarboxylase activity
      and decreased partitioning of cysteinesulfinate to taurine vs. sulfate. Thus,
      sulfur amino acids may be less effective than protein in decreasing
      cysteinesulfinate decarboxylase activity and may result in a pattern of sulfur
      catabolite production from cysteine that favors taurine production.

PMID- 7722698
TI  - Biotin accounts for only half of the total avidin-binding substances in human
      serum.
AB  - In studies using an avidin-binding assay to measure the serum or plasma
      concentration of biotin, biotin is sometimes assumed to be equal to the avidin
      binding substances detected. To provide a range of values for serum
      concentrations of biotin, bisnorbiotin, and biotin sulfoxide, HPLC was used to
      separate avidin-binding substances in human serum, and the chromatographic
      fractions were assayed for avidin-binding substances (biotin and biotin
      metabolites). In sera from 15 normal fasting adults, substantial concentrations
      of avidin-binding substances other than biotin were detected. Two of the
      principal substances were identified as bisnorbiotin and biotin sulfoxide based
      on their chromatographic properties. The serum concentrations of bisnorbiotin and
      biotin sulfoxide varied widely among the individuals. In three subjects, the
      concentration of bisnorbiotin exceeded that of biotin. The presence of avidin
      binding substances in addition to biotin may have confounded previous
      measurements of the concentration of biotin in serum, plasma, and blood when
      avidin-binding assays were used. Because bioassay methods for biotin sometimes
      use organisms for which one or more of these biotin metabolites are growth
      factors, measurements of biotin in blood using some bioassays are likely to
      overestimate the concentrations of biotin.

PMID- 7722699
TI  - Free amino acids can replace protein-bound amino acids in test diets for studies
      in rainbow trout (Oncorhynchus mykiss).
AB  - Effects of reducing dietary concentration of protein-bound amino acids on growth,
      feed intake and composition of gain in rainbow trout were studied in four
      experiments. Average initial body weights ranged between 29 +/- 0.7 and 55 +/-
      0.5 g per trout. Diets contained approximately 20 MJ digestible energy/kg dry
      matter. Each diet was fed to satiation to four replicate groups of 20 trout. Feed
      intake and growth rates were recorded for each group. Body composition was
      analyzed in representative groups at the start of each experiment and in all
      experimental groups at the end of each experiment. Reduction of dietary protein
      concentration to < 380 g/kg dry matter caused significantly lower growth rates
      and reduced protein concentrations of gain, but these reductions in growth could
      be offset by the addition of 10 crystalline essential amino acids. Fish meal was
      completely replaced by a mixture of wheat gluten and crystalline amino acids
      without negative influences on growth. In the absence of fish meal, almost half
      the wheat gluten could be replaced by crystalline amino acids in diets containing
      about 32 g N x 6.25/kg dry matter without significant influences on growth. In
      such diets, concentrations of individual amino acids may be varied widely with no
      variation in other amino acids or nutrients.

PMID- 7722700
TI  - Response of rainbow trout (Oncorhynchus mykiss) growing from 50 to 150 g to
      supplements of DL-methionine in a semipurified diet containing low or high levels
      of cystine.
AB  - We studied the effect of increasing dietary concentrations of DL-methionine on
      growth, feed intake, feed conversion ratio and the composition of gain in rainbow
      trout. Twenty-four groups of 20 trout initially weighing 51 +/- 0.5 g/trout were
      fed semipurified diets containing 20.1 MJ digestible energy and either 3.0 or 5.8
      g cystine/kg dry matter. At each level of cystine, 12 levels of methionine (2 to
      11 g/kg dry matter) were achieved by supplementation with graded quantities of DL
      methionine. During an experiment of 49 feeding days, no significant effect of the
      level of dietary cystine was found for any performance trait. Nonlinear responses
      to increasing dietary methionine concentrations were found for feed intake,
      growth rate, protein concentration of gain and protein deposition, whereas fat
      concentration of gain decreased concurrently. Dietary methionine was utilized
      most efficiently at a concentration of 3.5 g methionine/kg dry matter or 0.17
      g/MJ digestible energy. Ninety-five percent of the plateau deposition of body
      protein was achieved at a dietary methionine concentration of 8 g/kg dry matter
      or 0.40 g/MJ digestible energy. For achieving 98%, the required concentration was
      9.0 g/kg or 0.49 g/MJ. Recommended dietary methionine concentration will depend
      on the trait chosen.

PMID- 7722701
TI  - Response of rainbow trout (Oncorhynchus mykiss) growing from 50 to 170 g to
      supplements of either L-arginine or L-threonine in a semipurified diet.
AB  - We studied the effects of increasing dietary concentrations of either L-arginine
      or L-threonine on growth, feed intake, feed conversion ratio and composition of
      gain in rainbow trout. Semipurified diets containing 20.1 MJ digestible energy/kg
      dry matter, with wheat gluten and crystalline amino acids as sole sources of
      amino acids, were fed to rainbow trout (initial mean body weight 47 +/- 0.7 g).
      In one series of 12 diets, arginine concentration ranged from 5.0 to 23.8 g/kg
      dry matter; in a second series of 12 diets, threonine concentration ranged from
      3.7 to 21.0 g/kg dry matter. Each diet was fed to a group of 20 fish. During the
      experiment of 51 feeding days, dry matter intake, weight gain, feed conversion
      ratio, protein concentration of gain and total protein deposition followed
      exponential functions. For achieving 95% of the potential maximum protein
      deposition, dietary concentrations of 11.6 g arginine and 10.4 g threonine/kg dry
      matter were required. Arginine and threonine were both utilized most efficiently
      at dietary concentrations of approximately 6 g/kg dry matter. At low dietary
      concentrations of arginine, deposition of this amino acid exceeded the quantity
      fed. Recommended dietary concentrations of arginine and threonine will depend on
      the trait desired in the trout.

PMID- 7722702
TI  - Carbohydrate utilization and digestibility by tilapia, Oreochromis niloticus x O.
      aureus, are affected by chromic oxide inclusion in the diet.
AB  - A 12-wk feeding trial was conducted to study the influence of chromic oxide
      (Cr2O3) on carbohydrate utilization and digestibility by tilapia, Oreochromis
      niloticus x O. aureus. Two levels of chromic oxide (0.5 and 2%) were each
      incorporated into diets containing glucose or starch. Chromic oxide was added at
      0 or 8 wk. The diets were fed to triplicate groups of fish weighing 1.11 +/- 0.05
      g. Fish fed the starch diet had greater (P < 0.05) weight gain, feed efficiency
      ratio, protein efficiency ratio, protein deposition and digestibility of protein,
      lipid, carbohydrate and dry matter than fish fed the glucose diet irrespective of
      the time and level of chromic oxide supplementation. Fish fed the glucose diet
      with 0.5% chromic oxide had higher weight gain, feed efficiency ratio, protein
      efficiency ratio and protein deposition than fish fed the glucose diet with 2%
      chromic oxide. The ingredient digestibility estimated using 0.5% chromic oxide as
      the marker was greater than that estimated with 2% chromic oxide. Higher
      phosphofructokinase and lower glucose-6-phosphatase activity was found in fish
      fed the starch diet than in fish fed the glucose diet regardless of the time and
      level of chromic oxide inclusion. Fish fed the glucose diet with 0.5% chromic
      oxide had higher phosphofructokinase activity and lower tissue chromium
      concentration than fish fed the glucose diet with 2% chromic oxide irrespective
      of chromic oxide inclusion time. These data suggest that the level of chromic
      oxide in the diet alters glucose utilization by tilapia and affects nutrient
      digestibility by tilapia. The time of chromic oxide inclusion had no effect on
      carbohydrate utilization and digestibility.

PMID- 7722703
TI  - Nutrient infusion into the ileum of rats does not lower plasma lipids or alter
      apolipoprotein mRNA abundance.
AB  - Viscous polysaccharides enhance the delivery of nutrients to the ileum. Our
      objective was to determine if the presence of nutrients in the ileum, in the
      absence of fiber, alters plasma and hepatic lipids. Twenty-four Wistar male rats
      weighing 150-160 g were fed a fiber-free purified diet (30% of energy as fat) for
      7 d. The small intestine was cannulated 30 cm proximal to the ileo-cecal
      junction. The animals consumed the purified diet ad libitum and the intestine was
      infused (3 mL/h) with saline, or an enteral solution contributing 10, 20 or 30%
      total energy for half of a 12-h feeding period. Infusion was performed for 14 d,
      after which the animals were killed. The animals adjusted their food intake so
      that each group had an equivalent energy intake and weight gain over the
      experimental period. The relative ileal mucosa weight was increased with nutrient
      infusion indicating hypertrophy. Plasma cholesterol in the nutrient-infused
      animals tended to be higher than in the saline-infused animals (P < 0.06).
      Apolipoprotein B and A-IV mRNA were not affected by ileal infusion. Thus,
      enhanced delivery of nutrients to the ileum, without fiber present in the diet,
      does not lower plasma cholesterol.

PMID- 7722705
TI  - The effects of improved nutrition in early childhood: the Institute of Nutrition
      of Central America and Panama (INCAP) follow-up study.

PMID- 7722704
TI  - Dietary calcium and lead interact to modify maternal blood pressure,
      erythropoiesis, and fetal and neonatal growth in rats during pregnancy and
      lactation.
AB  - We studied the effects of dietary calcium and lead exposure on lead toxicity,
      fetal and neonatal growth, erythropoiesis and blood pressure during pregnancy and
      lactation in rats. Pregnant Sprague-Dawley rats (n = 43) were randomly assigned
      to one of six treatment groups of 7-8 rats each. Half of the rats were fed diets
      of low (0.1%), normal (0.5%) or high (2.5%) calcium as calcium carbonate and
      exposed to 250 mg/L of lead in their drinking water for the duration of the
      pregnancy and for 1 wk of lactation. Three control groups were fed the same diets
      without lead exposure. Pups were studied at 1 d and 1 wk of age. Maternal and
      fetal blood and organ samples from the groups fed the low calcium diet had the
      highest lead concentrations, whereas the lowest lead concentrations were found in
      the groups fed the high calcium diet. Dam and pup hemoglobin concentrations,
      hematocrits, and body weights and lengths were reduced by lead exposure and by
      the high calcium diet. The latter also reduced organ iron concentrations and
      prevented lead-induced increases in free erythrocyte protoporphyrin. Dam systolic
      blood pressures during the third trimester of gestation were significantly higher
      in rats exposed to lead and fed the low calcium diet than in rats in the other
      five treatment groups. The results demonstrate that dietary calcium and lead
      exposure interact in rats to influence maternal blood pressure, erythropoiesis,
      and fetal and neonatal growth during pregnancy and lactation.

PMID- 7722706
TI  - Nutritional impact of supplementation in the INCAP longitudinal study: analytic
      strategies and inferences.
AB  - From 1969 to 1977 a supplementation trial was conducted in Guatemala to ascertain
      the effects on physical and behavioral outcomes of improved nutrition in pregnant
      women and in preschool children. This paper reviews different strategies to
      analyze the effect of the intervention on physical growth. One strategy compares
      outcomes in two villages that were randomly allocated to receive Atole, a
      supplement containing high amounts of protein and energy, with values in two
      other villages that received Fresco, a beverage containing no protein and little
      energy. Both supplements contained micronutrients. This comparison of village
      means gives a probability significance statement (P < 0.005) that the difference
      in growth was because of the supplement intervention, although it does not
      specify the aspect of the intervention that caused the effect. Complementary
      strategies increase the credibility that the effect of the supplement was
      nutritional. Thus, analysis of the dose response with increasing supplement
      intake within the villages excludes the possibility that the above findings were
      the result of knowing which villages received which supplement (i.e., measuring
      biases). A greater effect in those most likely to respond nutritionally also
      increases the credibility that the mechanism was nutritional. In studying other
      behavioral and biomedical impacts of this supplementation intervention, analyses
      for credibility should always be included.

PMID- 7722707
TI  - Age differences in the impact of nutritional supplementation on growth.
AB  - Supplementary feeding programs are common in developing countries. These programs
      often cannot demonstrate an impact on child growth, however, possibly because
      they tend to reach older children. This study examines the impact of nutritional
      supplementation on annual growth rates in length and weight from birth to 7 y of
      age in 1208 rural Guatemalan children. A series of multiple linear regression
      models is used to control for initial body size, diarrheal disease, home diet,
      socioeconomic status and gender. During the first year of life, each 100 kcal/d
      (418 kJ) of supplement was associated with approximately 9 mm in additional
      length gain and 350 g in additional weight gain; the benefit decreased to
      approximately 5 mm in length gain and 250 g in weight gain during the 2nd y of
      life. Between 24 and 36 mo of age, supplement only had a significant impact on
      length. There was no impact of nutritional supplementation on growth between 3
      and 7 y of age. Patterns were the same if supplement intakes were expressed as a
      percent of recommended allowances or growth was expressed as a percent of the
      expected rate. These impacts of nutritional supplementation on growth coincide
      with the ages when growth velocities, as well as growth deficits, are greatest in
      this population.

PMID- 7722708
TI  - Patterns of linear growth in rural Guatemalan adolescents and children.
AB  - Length and weight data from a longitudinal study of rural Guatemalan subjects
      birth to 7 y of age and height and weight data from a cross-sectional study of
      the same subjects when they were 11-24.9 y old are compared to reference data for
      the USA general population and for Mexican-Americans. At birth, the median length
      of Guatemalan children is at approximately the 16th percentile of the USA
      reference or approximately 2 cm shorter. By 6 mo of age, Guatemalan children are
      shorter, on average, than the 5th percentile of the reference curves and, in
      absolute terms, are approximately 5 cm below the median; by 3 y, the difference
      increases to approximately 10 cm. As adults, Guatemalans have about the same
      absolute level of deficit (approximately 13 cm) as they did at age 3 y. If the
      general USA population is used for comparison, Guatemalans can be said to grow as
      expected during adolescence, neither recuperating the growth retardation of early
      childhood nor falling further behind in size. If the Mexican-American sample is
      selected instead, it would appear that some catch-up in growth occurs in
      Guatemalan adolescents. Regardless of the choice of reference population, growth
      is markedly retarded only in early childhood; adolescence is not a period when
      growth is significantly constrained.

PMID- 7722709
TI  - Nutritional supplementation during the preschool years influences body size and
      composition of Guatemalan adolescents.
AB  - Effects of supplementary feeding during early childhood on body size and
      composition at adolescence are examined in a population with marked growth
      failure in the first 3 y of life. The data came from a supplementation trial
      conducted in rural Guatemala from 1969 to 1977 and a 1988-89 follow-up study of
      the same subjects at adolescence. Two pairs of villages participated in the
      trial. One village from each pair received a high protein-energy supplement
      (Atole), which significantly improved dietary intakes, whereas the other village
      of the pair received a low-energy, no-protein supplement (Fresco), which did not
      impact appreciably on dietary intakes. Children from Atole villages grew better
      during the preschool period than children from Fresco villages. At adolescence,
      subjects from Atole villages were taller, weighed more and had greater fat-free
      masses than subjects from Fresco villages. Differences in height at adolescence
      were slightly reduced in magnitude relative to differences at 3 y of age.
      However, differences in weight were increased in adolescence relative to 3 y of
      age.

PMID- 7722710
TI  - Nutritional supplementation during the preschool years and physical work capacity
      in adolescent and young adult Guatemalans.
AB  - A follow-up study (1988-89) was carried out in 364 rural Guatemalans, 11-27 y of
      age, who earlier had participated in a nutritional supplementation experiment.
      Among its objectives was the assessment of the long-term effects of the nutrition
      intervention on physical work capacity. Subjects and their mothers from two
      villages had available a high-energy, high-protein supplement (Atole: 163
      kcal/682 kJ and 6.4 g protein per serving or 180 mL), whereas in two other
      villages a low-energy, no-protein supplement (Fresco: 59 kcal/247 kJ per 180 mL)
      was provided. Consumption was ad libitum. Maximum oxygen consumption (VO2max) at
      follow-up was significantly greater in Atole compared with Fresco subjects of
      both sexes. In subjects 14-19 y, exposed to supplementation throughout gestation
      and the first 3 y of life, Atole males had a significantly higher VO2max (2.62
      L/min) than Fresco males (2.24 L/min), the differences remaining significant even
      after controlling for body weight and fat-free mass; also, there was a
      significant positive relationship between amount of supplement consumed and
      VO2max. The supplementation effect in females of similar age was not
      statistically significant. It is concluded that early nutritional improvements
      can have long-lasting effects on physical performance.

PMID- 7722711
TI  - Age at menarche and nutritional supplementation.
AB  - Retrospective data on age at menarche were collected for 832 Guatemalans 15-30 y
      in age to test whether exposure to a high energy and high protein supplement
      (Atole: 163 kcals/682 kJ and 11.5 g protein per cup or 180 mL) during childhood
      led to earlier menarche than did exposure to a low energy, no protein supplement
      (Fresco: 59 kcals/247 kJ in 180 mL). Mean age at menarche was similar in Atole
      (13.75 +/- 1.22 y; mean +/- SD) and Fresco (13.74 +/- 1.36 y) groups. The
      corresponding value for immigrants (n = 144), subjects not exposed to the
      supplements, was 13.55 +/- 1.20 y. Year of birth as well as socioeconomic status
      (SES) were associated with age at menarche. Age at menarche declined by 0.69 y
      over the 15-y period and menarche occurred earlier in higher SES households.
      Significant positive interactions between supplement type and SES and between
      supplement type and year of birth were found, but plausible explanations for them
      could not be advanced.

PMID- 7722712
TI  - Early nutritional supplementation and skeletal maturation in Guatemalan
      adolescents.
AB  - The effect of early childhood nutritional supplementation on skeletal maturation
      at adolescence was investigated in 663 rural Guatemalans, aged 11-18 y. Skeletal
      maturation was assessed by the Tanner-Whitehouse-2 method. The subjects were
      former participants in the Institute of Nutrition of Central America and Panama
      longitudinal study of growth and development (1969-77) residing in four villages
      (two large and two small) in eastern Guatemala. The villages were randomized
      within pairs to receive either a high energy, high protein supplement (Atole) or
      a low energy supplement with no protein (Fresco). Skeletal maturity was observed
      across all villages to be delayed significantly relative to a British reference
      for boys < 14 y of age, but not for older boys or for girls < 14 y of age. Delays
      in girls > 14 years could not be determined reliably because many had reached
      maturity. Girls < 14 years from Atole villages were more advanced in skeletal
      maturity than similar age girls from Fresco villages but these differences were
      found only in comparisons of the large villages. The relationship between early
      nutrition and biological maturation at adolescence may be obscured in this sample
      by the advanced age at which the subjects were examined in adolescence.

PMID- 7722713
TI  - Nutritional supplementation during early childhood and bone mineralization during
      adolescence.
AB  - To assess the long-term impact of nutritional supplementation on bone
      mineralization during adolescence, we studied 356 Guatemalan adolescents who
      participated from birth to 7 y of age in a controlled supplementation trial. Bone
      mineralization of the distal radius was assessed using single photon
      absorptiometry. Children who consumed more cumulative energy from the supplement
      during childhood had greater bone mineral content, bone width and bone mineral
      density during adolescence than those who consumed less energy. The associations
      remained after controlling for each subject's age and gender, and for the type of
      supplement consumed, but became statistically nonsignificant after adjusting for
      weight and stature. Because intake of supplement also was associated positively
      with weight and stature during adolescence, it is concluded that supplementing
      malnourished children can have a demonstrable long-term impact on bone
      mineralization, but that the effects are probably not beyond those due to
      improvements in overall somatic growth associated with supplementation.

PMID- 7722714
TI  - Changing concepts in the management of chronic pain.

PMID- 7722715
TI  - Neurosensory disturbances of the trigeminal nerve: a long-term follow-up of
      traumatic injuries.
AB  - PURPOSE: This study assesses the physical and psychosocial consequences of
      trigeminal nerve damage. MATERIAL AND METHODS: A questionnaire consisting of 33
      questions, 30 of which had fixed alternatives, was mailed to 300 persons who had
      received compensation from a syndicate of several insurance companies (Konsortiet
      for Patientforsakring) because of trigeminal nerve damage. One question with no
      alternative reply gave the respondents an opportunity to comment on their
      problems and to rate them on a visual analogue scale. The questionnaire was
      answered by 226 recipients, 72 men and 153 women. RESULTS: Most of the patients
      had sensory disturbances resulting from damage to the inferior alveolar nerve,
      the mental nerve, or the lingual nerve. More than 70% of the respondents
      complained about paresthesia. No fewer than one of five patients suffered from
      pain in the affected area. The altered sensation caused functional disturbances
      in speech and eating which, in turn, had social and psychological consequences.
      CONCLUSIONS: This study shows that mainly women and older persons have the most
      severe discomfort after oral nerve damage.

PMID- 7722716
TI  - Surgical management of benign tumors of the submandibular gland: a follow-up
      study.
AB  - PURPOSE: This retrospective study evaluated data pertaining to history, symptoms,
      diagnosis, and mode of therapy of patients treated for benign tumors of the
      submandibular gland. PATIENTS AND METHODS: The records of 38 patients were
      reviewed. The patients were divided into three groups: pleomorphic adenoma (first
      operation), pleomorphic adenoma (second operation for recurrence), and other
      tumors. Follow-up was done by questionnaires sent to the patient and referring
      doctor. RESULTS: The vast majority of patients treated (92%) had had either a
      first or second operation for pleomorphic adenoma. Follow-up revealed that
      recurrence did not develop in the group of patients with primary surgery.
      However, one patient undergoing surgery for recurrent pleomorphic adenoma
      developed two recurrences. Two patients suffered from slight weakness of the
      lower lip. CONCLUSION: Tumor recurrence was found only in the cases of second
      operation after previous surgery for pleomorphic adenoma. Therefore, the first
      operation should extirpate the entire gland to minimize the risk of recurrence.

PMID- 7722717
TI  - Infected screws in patients treated by mandibular sagittal split osteotomy.
AB  - PURPOSE: The relationship of third molar extraction at the time of mandibular
      sagittal split surgery to infection or exposure of the rigid fixation hardware
      was studied. MATERIALS AND METHODS: The records of 83 patients who had sagittal
      split surgery between July 1987 and July 1991 were reviewed. The groups were
      divided into those who did or did not have third molar extraction during sagittal
      split surgery. Those patients who developed infection or exposure of their
      hardware were identified. RESULTS: Of the 83 patients, 15 had infection or
      exposure of their hardware. Eleven of them (73.3%) had third molar extraction at
      the time of sagittal split surgery. In the uninfected/unexposed group, 26 of 68
      (38.2%) had third molar extraction during their operation. These differences were
      highly significant (P < .05). CONCLUSION: This study shows a definite
      relationship between infected and exposed hardware after sagittal split surgery
      and intraoperative removal of third molars, and suggests that the third molars
      should be removed well in advance of surgery to reduce this complication.

PMID- 7722718
TI  - Baseball bat injuries to the maxillofacial region caused by assault.
AB  - PURPOSE: Baseball bats, although meant for recreational use, are also frequently
      used as assault weapons, resulting in multiple types of injuries including those
      in the maxillofacial region. This report reviews the patients admitted to the
      Maryland Institute of Emergency Medical Service with maxillofacial injuries
      caused by blunt trauma from assault with a baseball bat between July 1989 and
      January 1994. PATIENTS AND METHODS: Records of 29 patients were reviewed for age,
      sex, race, Glasgow Coma Scale, associated drug or alcohol use, type of injury,
      and associated injuries. RESULTS: In this inner city hospital study it was found
      that 18 of the patients (62%) were African-American and that 74% of the victims
      had associated alcohol abuse and 38% had associated drug abuse. Of the 29
      patients, 27 (93%) were men and 23 (79%) were between the ages of 21 and 40
      years. The majority of fractures involved the midface region and nearly half the
      patients had concomitant neurologic injury. Two patients died as a result of
      their injuries. CONCLUSION: Assaults with a baseball bat can result in
      significant morbidity and even mortality.

PMID- 7722719
TI  - Myxoma in childhood: an analysis of 10 cases.
AB  - PURPOSE: The object of this study was to present a series of myxoma in children
      and to evaluate possible differences between young and adults patients. MATERIALS
      AND METHODS: All tumors of patients under 16 years of age (10 cases), were
      separated from the 80 myxomas found in the Oral Pathology Laboratory, Faculty of
      Odontology, Buenos Aires University, and were analyzed in terms of clinical data,
      radiographic image, histopathology, treatment, and evolution. RESULTS: Myxoma in
      childhood represented 12.5% of the 80 cases in our series. The mean age was 11.6
      years. Six patients were boys and four were girls. Both jaws were affected
      equally, predominantly in the premolar-molar region. Eighty percent of the tumors
      were larger than 2 cm. Only one case was clinically diagnosed as myxoma.
      Radiologically the most frequent image was unilocular with cortical expansion and
      tooth displacement. Histologically seven cases were diagnosed as myxoma and three
      as fibromyxoma. Treatment involved surgical resection in most cases. Two patients
      showed recurrence within the first year after surgery. CONCLUSIONS: The frequency
      of myxoma in childhood may be higher than that of other aggressive odontogenic
      tumors, although some literature refers to this tumor as very uncommon in
      children. Clinically this tumor may not always be taken into account in the
      differential diagnosis of intraosseous radiolucencies in young patients. The
      histologic appearance is similar in young and adult patients, but myxoma in
      children may be larger. It was not possible to correlate the histologic type of
      myxoma and the age of the patients.

PMID- 7722720
TI  - Diagnosis of unsuspected facial fractures on routine head computerized
      tomographic scans in the unconscious multiply injured patient.
AB  - PURPOSE: This article assessed the value of routine head computerized axial
      tomographic (CT) scans for diagnosis of unsuspected facial fractures and its
      clinical implications in the multiply injured patient who is intubated,
      unconscious, or sedated at the time of initial assessment and requires a head CT
      scan to assess for brain injury. METHODS: At a level I trauma center from June 1,
      1992 to June 1, 1993 all intubated blunt trauma patients who required routine CT
      scan evaluation at initial assessment were studied prospectively. Routine
      scanning started at the foramen magnum and included the maxilla. Patients who
      died within the first 24 hours were excluded. RESULTS: The study population
      included 116 patients (85 male, 21 female) aged 12 to 85 years (mean, 28 years)
      with injury severity scores ranging from 1 to 50 (mean, 23). The mechanism of
      injury was: motor vehicle accidents (n = 74), motorcycling (n = 5), pedestrians
      accidents (n = 13), falls (n = 10), bicycling (n = 5), assaults (n = 8), and
      boating accident (n = 1). There were 19 suspected facial fractures; 18 required
      surgical repair. There were 27 unsuspected facial fractures; 13 required surgical
      care. Three suspected fractures were ruled out. CONCLUSION: Routine head CT scans
      to assess for brain injury in the multiply injured patient are also very useful
      in the diagnosis of unsuspected facial fractures, almost half of which will
      require surgical intervention.

PMID- 7722721
TI  - Midface advancement in sheep by gradual distraction: a 1-year follow-up study.
AB  - PURPOSE: The purpose of this study was to find a solution to the unsatisfactory
      postoperative maxillary relapse after major maxillary advancement or inferior
      repositioning of the maxilla. MATERIALS AND METHODS: Major midface advancement by
      gradual distraction was performed on three young adult sheep over 21 days. Using
      an external device, the midface was advanced 36 mm in the nasofrontal area and 43
      mm in the lateral aspect of the maxilla. The apparatus remained as an external
      fixation device for 6 weeks after the distraction to allow better ossification.
      After removal of the device, a 1-year clinical and radiographic follow-up was
      conducted. RESULTS: Direct measurements between the markers showed 2- to 3-mm
      relapse after 1 year. Radiologic measurements demonstrated that the relapse
      occurred during the first 3 months after removal of the distraction apparatus.
      CONCLUSION: It was concluded that midface advancement by gradual distraction may
      obviate the need for bone grafting and offer a greater movement of bone segments
      with good skeletal stability.

PMID- 7722722
TI  - Expression of matrix metalloproteinase-3 in stage I and II squamous cell
      carcinoma of the oral cavity.
AB  - PURPOSE: The object of this study was to evaluate the significance of matrix
      metalloproteinase-3 (MMP-3) in tumor invasion and metastasis of early squamous
      cell carcinoma (SCC) of the oral cavity. MATERIALS AND METHODS: Surgical
      specimens from 65 patients with stage I and II SCC of the oral cavity were the
      subjects of this study. Tissue specimens were fixed in formalin and embedded in
      paraffin, and the sections were stained with monospecific antibodies against
      human MMP-3 by the avidin-biotin-peroxidase complex method. RESULTS: Of the 65
      patients, 30 (46.2%) tested positive for MMP-3. Immunoreactivity revealed the
      expression of MMP-3 to be in the small cancer nests in the advancing front of
      invasion, but not in normal oral epithelium. MMP-3 expression was positively
      correlated with tumor size, depth of tumor invasion, diffuse invasive mode, and
      the high incidence of lymph node metastasis. CONCLUSION: MMP-3-containing tumors
      will invade adjacent normal tissues more aggressively, including lymphatic and
      blood vessels. Therefore, the examination of MMP-3 expression in biopsy specimens
      should provide information useful in predicting the malignant potential of early
      SCC of the oral cavity.

PMID- 7722723
TI  - The use of a collagen sheet as a disc replacement in the rabbit temporomandibular
      joint.
AB  - PURPOSE: This study evaluated a biocompatible, preformed collagen sheet as a disc
      replacement after temporomandibular joint (TMJ) surgery in the rabbit and
      compared its performance with that of an autogenous dermal graft. MATERIALS AND
      METHODS: Twenty adult New Zealand white rabbits were divided into four groups of
      five animals: 1) nonoperated control; 2) TMJ discectomy without replacement; 3)
      discectomy with dermal graft replacement; and 4) discectomy with collagen sheet
      replacement. Each operated animal had the same procedure bilaterally. Rabbits
      were killed at 2, 4, 8, 18, and 36 weeks after surgery and the TMJs were
      surgically removed en bloc, decalcified, sectioned, and stained for histologic
      evaluation. RESULTS: There was significant articular destruction in the
      discectomized joints with no disc replacement. Both the dermal and collagen disc
      replacements were resorbed by the eighth week and the articular surfaces
      exhibited cartilaginous hyperplasia, which returned to near normal thickness by
      the 18th week. CONCLUSION: This study demonstrated that both a collagen sheet and
      a dermal graft may act in a protective capacity and may help retard early
      degenerative changes normally seen in the articular surfaces of discectomized
      TMJs.

PMID- 7722724
TI  - Enlargement of the rabbit mandibular condyle after experimental induction of
      anterior disc displacement: a histomorphometric study.
AB  - PURPOSE: Clinical and autopsy studies have shown that patients with
      temporomandibular joint dysfunction are more likely to have enlargement and
      deformity of the condyle and subsequently occlusal disharmony. However, it is not
      known what causes this enlargement. This study was designed to test the
      hypothesis that surgical induction of anterior disc displacement (ADD) in the
      rabbit craniomandibular joint (CMJ) could lead to enlargement and deformity of
      the condyle. MATERIALS AND METHODS: The right CMJ was exposed surgically, and the
      discal attachments were severed except for the posterior discal attachment
      (bilaminar zone). Then, the disc was repositioned anteriorly and sutured to the
      zygomatic arch. The left joint served as a sham-operated control. CMJ tissues
      then were removed after fixation at 24 hours (5 rabbits), 1 week (10 rabbits), 2
      weeks (10 rabbits), or 6 weeks (10 rabbits), processed, and stained with
      hematoxylineosin. Histomorphometric assessment was used to evaluate changes in
      condylar volume, and thickness of the fibrous, reserve cell, and condylar
      cartilage layers. RESULTS: The results showed a progressive enlargement of the
      condylar volume in all experimental joints compared with controls (P < .01). The
      enlargement was attributable to a significant increase in the cartilage thickness
      and surface area of the nonarticulating portion of the condyle in the 1-week
      group (P < .01). In the 2- and 6-week groups, there were significant, progressive
      increases in cartilage thickness and surface area of the articulating portion of
      the condyle (P < .01). In all animals, increased cartilage thickness was
      associated with a decrease in the thickness of the fibrous and the reserve cell
      layers (P < .01). CONCLUSION: It is concluded that surgical induction of ADD in
      the rabbit CMJ causes enlargement of the condyle, which is in part caused by
      hyperplasia of the condylar cartilage.

PMID- 7722725
TI  - Anterior maxillary advancement using tooth-supported distraction osteogenesis.
AB  - PURPOSE: This study used the principle of distraction osteogenesis to advance the
      anterior maxilla of the dog using a totally tooth-supported distraction device.
      MATERIALS AND METHODS: After an anterior maxillary osteotomy, the distraction
      device was activated 0.5 mm every 12 hours to advance the anterior segment 10 mm
      in 10 days. RESULTS: Serial tooth and radiographic measurements indicated that on
      the 10th day the average tooth advancement was 8.4 mm +/- 1.5 mm and the average
      skeletal advancement was 4.0 mm +/- 1.5 mm. After 6 weeks the average tooth
      advancement was 7.2 +/- 1.6 mm and the average skeletal advancement was 3 +/- 1.3
      mm. At 3 months the tooth advancement was 6.2 +/- 1.5 mm and at 6 months the
      tooth advancement was 5.0 +/- 1.1 mm. Bone healing was present in all animals.
      CONCLUSION: This results of this study indicate that a tooth-borne maxillary
      distraction device will result in significantly greater dental movement than
      skeletal movement and that skeletal fixation may be needed for appliances used to
      advance the maxilla.

PMID- 7722726
TI  - Experimental reconstruction of mandibular defects with vascularized iliac bone
      grafts.
AB  - PURPOSE: The study evaluated the processes of incorporation and bone remodeling
      after microsurgical transplantation of iliac crest grafts for mandibular defect
      reconstruction. MATERIALS AND METHODS: A defect in the mandibular angle measuring
      2 x 4 x 1 cm was reconstructed in six Gottingen minipigs with a microvascularized
      iliac bone graft based on the circumflex artery. The animals were killed at 14,
      28, and 56 days after transplantation and the healing process was histologically
      examined. RESULTS: Although a constant vascular supply to the graft was restored
      by the microvascular reanastomosis, necrosis occurred in the major part of the
      bone marrow. New bone formation from the graft was markedly delayed compared with
      that from the mandible. Some osteocytes and marrow survived after grafting, but
      the volume of iliac bone tended to decrease gradually over time. In the 56-day
      specimens, the border between the graft and the mandible was not clear.
      CONCLUSION: These findings indicate that survival of the vascularized iliac bone
      graft in the minipig is not complete.

PMID- 7722727
TI  - Orthognathic surgery versus orthodontic camouflage in the treatment of mandibular
      deficiency.
AB  - Surgical correction of Class II malocclusions, when associated with mandibular
      deficiency, often has improved results with combined orthodontic and surgical
      correction compared with orthodontic treatment alone. Strong consideration of
      surgical correction of mandibular deficiency should be based on the following
      questions: 1) Do the patient's goals for treatment place a high priority on
      improvement in facial esthetics? As a corollary, even patients who are not
      particularly concerned with facial esthetics, but who may have a worsening in
      facial appearance as a result of orthodontic camouflage, should be considered for
      surgical correction. This may include patients with lack of upper lip support, an
      obtuse nasolabial angle, a large nose, and a long lower face height, all of which
      may become more apparent as a result of orthodontic camouflage treatment. 2) Are
      the orthodontic movements required in excess of the envelope of discrepancy so
      that adequate orthodontic correction may not be achieved? 3) Could orthodontic
      surgical treatment result in a significant decrease in treatment time? An example
      would be when surgical treatment in combination with orthodontics could be
      accomplished without extraction, whereas orthodontic treatment alone would
      require extraction and space closure. 4) Is there adequate patient compliance?
      Would orthodontic treatment alone be as ineffective without adequate patient
      cooperation? 5) Are the risks of surgery within acceptable levels? Are the
      benefits of surgical treatment, as previously described, obvious?

PMID- 7722728
TI  - Orthodontic camouflage versus orthognathic surgery in the treatment of mandibular
      deficiency.
AB  - Clearly, there are postpubertal patients with Class II malocclusions for whom
      orthognathic surgery combined with orthodontics is the "best" option, but
      epidemiologic information suggests they are a relatively small percentage of the
      potential patient pool. The majority of patients fall into either an orthodontic
      treatment group or a borderline category. Many of these can be treated
      successfully with orthodontic camouflage. Research has shown psychosocial factors
      play a major role in determining the patient's selection of a treatment option.
      This emphasizes the need for careful attention to global psychologic factors,
      with special emphasis on patient concerns regarding body image. Morphometric
      criteria have been offered describing appropriate candidates for orthodontic
      camouflage. These are supported by a combination of research and clinical
      experience. Patients who do not fit these criteria should not automatically be
      considered candidates for surgery. Psychosocial research suggests a percentage of
      these individuals place less importance on facial change and are content to
      improve dental esthetics and function to the degree possible. To assist in the
      decision-making process, patients should be given the best information available
      regarding potential outcome. Currently this may involve treatment simulation
      using a combination of computer images and dental models. Caution has been
      suggested, given the variability associated with predicting soft tissue change.
      There are additional legal concerns regarding the implied guarantee of treatment
      outcome. Correspondingly, the influence of this technology must be kept in
      perspective. Recent research on the decision-making process found computer
      imaging to be an important factor in only 24% of the patients studied.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7722729
TI  - Ankyloglossia superior: report of a case.

PMID- 7722731
TI  - Infraorbital nerve sharing to restore sensibility to the lower lip: case report.

PMID- 7722730
TI  - Peripheral ameloblastoma: case report and review of literature.

PMID- 7722732
TI  - Botryomycosis with orbital invasion: case report and literature review.

PMID- 7722733
TI  - Pleomorphic adenoma in the parapharyngeal space: report of three cases.

PMID- 7722734
TI  - Rare complications of an odontogenic abscess: mediastinitis, thoracic empyema and
      cardiac tamponade.

PMID- 7722735
TI  - Clear cell odontogenic carcinoma of the mandible: report of a case.

PMID- 7722736
TI  - Multiple schwannomas of the neck, mediastinum, and parapharyngeal space: report
      of case.

PMID- 7722737
TI  - Integration of dental models in a three-dimensional replica.

PMID- 7722738
TI  - Simple device for plate positioning and contouring.

PMID- 7722739
TI  - In defense of the mandibular staple bone plate.

PMID- 7722740
TI  - The sealing of the tooth/amalgam interface by corrosion products.
AB  - A marginal gap exists between the amalgam restoration and the cavity walls. At
      this interface, there is a constant percolation of fluid containing ions,
      molecules and bacteria. With time, corrosion products of the amalgam components
      seal the gap at the amalgam/tooth interface. The corrosion processes for
      conventional and high copper amalgam and factors affecting the corrosion deposits
      are reviewed. Better amalgam adaptation to the cavity walls improves the chances
      of sealing the restoration by corrosion products. The effectiveness of cavity
      varnish in preventing microleakage until corrosive deposits are formed is
      discussed.

PMID- 7722741
TI  - The influence of a flexible coating on the bone stress around dental implants.
AB  - The influence of a three-layered flexible coating of Polyactive on bone stress
      distribution was investigated by three-dimensional finite element models of
      mandibular bone, in which a titanium implant (coated or uncoated) was located.
      Polyactive is a system of poly(ethylene oxide) poly(butylene terephthalate)
      segmented co-polymers with bone-bonding capacity. In the case of sagittal and
      transversal loading, the use of a Polyactive coating reduced both the minimum
      principal stress in the bone and the compressive radial stress at the bone
      implant interface. However, it raised the maximum principal and the tensile
      radial stress. In the case of vertical loading, the application of a flexible
      coating reduced the compressive radial stress at the bone-implant interface
      around the neck of the implant by a factor of 6.6 and the tensile radial stress
      by a factor of 3.6. Variations in composition and thickness of the coating did
      not affect the results significantly.

PMID- 7722742
TI  - Centre and magnitude of vertical forces in complete denture wearers.
AB  - The aim of this study was to examine the centre and magnitude of a vertical
      component of occlusal forces in complete denture wearers during several
      activities using a newly developed method. A lower complete denture was divided
      into upper and lower parts parallel to the occlusal plane. They were connected by
      four force transducers which were embedded in the first premolar and the second
      molar portions on both sides of the denture base. Forces were recorded during
      tapping, chewing peanuts and raisins, and clenching. The centre and the magnitude
      of the forces were calculated from forces recorded by the four transducers. The
      maximum error of the centre was 1 mm, and the maximum error of the magnitude was
      4%. The centre was observed between a first molar and the middle of the
      edentulous dental arch. Maximal mean value of the forces during chewing was 65
      110 N.

PMID- 7722743
TI  - A comparative electrochemical in vitro evaluation of the corrosion behaviour of
      dental amalgams.
AB  - The electrochemical corrosion behaviour of 16 currently marketed amalgams for
      dental fillings was studied in vitro. Depending upon the type of amalgam and the
      treatment of the filling the electrochemical corrosion currents derived from
      cyclic voltammograms varied over several orders of magnitude. Their change as a
      function of time was also very different. Suggestions are made for a stability
      rating of the products based on the results obtained.

PMID- 7722744
TI  - Ultrasonography of masseter muscle size in normal young adults.
AB  - The present study was planned to determine the relationship between linear
      dimensions of human masseter muscle cross-section and cross-sectional area (CSA),
      and to assess symmetry between the two sides in normal young adults. Cross
      sectional images of the masseter muscle were measured bilaterally by real-time
      ultrasound imaging in 39 healthy dentate subjects, 19 males and 20 females, aged
      21-47. From stored images, CSA and two linear measurements of muscle cross
      section were obtained (the shortest and the longest distance through the muscle
      group). Correlation and regression analyses were performed to examine the
      relationship between CSA and the linear dimensions (both individually and with
      the linear dimensions multiplied). Symmetry of CSA between the two sides of the
      face was examined using the paired t-test. The significance of correlation
      coefficients (r) and the difference between the slopes of the regression lines
      were also examined. Masseter CSA was larger in males than in females. All
      correlation values between CSA and linear measurements were significant but
      muscle CSA was most accurately predicted when the linear measurements were
      multiplied (r = 0.97; P < 0.001). Although the correlation in this regard was
      high, the linear dimensions consistently overestimated the actual CSA by
      approximately 25%. Males showed more symmetry of CSA than females. The range of
      values for symmetry of masseter CSA was too large to assess abnormal asymmetry in
      patients with unilateral symptoms.

PMID- 7722745
TI  - Stability of dental waxes following repeated heatings.
AB  - The flow and strength properties of dental waxes were examined following
      excessive and repeated heatings of the materials. For one product, the flow at 40
      +/- 0.5 degrees C was reduced by 25.3% following heating above 200 degrees C. A
      decrease of the elastic modulus at 20 +/- 1 degree C by approximately 66% was
      observed in some cases after the heating temperature had been increased to 300
      degrees C. Property variations were related to compositional changes, which were
      investigated by infrared spectoscopy and thermal analysis. Exposure of dental
      waxes to temperatures higher than 200 degrees C, particularly if it is repeated,
      may affect the composition and properties, resulting in inferior materials.

PMID- 7722746
TI  - Effect of working side interferences on mandibular movement in bruxers and non
      bruxers.
AB  - The effect of working interference on 13 bruxers and 14 non-bruxers was studied
      by applying a metal overlay on the buccal cusps of the adjacent upper premolar
      and molar. The pattern and velocity of cyclic movement during gum chewing before
      and after overlay insertion were observed. EMG of the temporalis and masseter
      muscles were recorded bilaterally during the chewing movement. It was found that
      after insertion, one of the non-bruxers complained of pain in the muscles, while
      such a complaint was not found in bruxers. Bruxing habit was reported to be less
      or eliminated in 44% of the bruxers, but no non-bruxers became bruxers. The
      closing velocity was more often decreased immediately after overlay insertion,
      and the closing path near the occlusal phase was significantly narrower, with
      patterns of over-extension and avoidance before reaching the occlusal phase. The
      delayed effects were a more vertically oriented chewing cycle without over
      extended closing movement, and an unretarded chewing velocity. It was concluded
      that within the experimental period a working side interference was tolerable in
      most of the subjects studied with or without a bruxing habit.

PMID- 7722747
TI  - Automated optical scanning for rapid sizing of chewed food particles in
      masticatory tests.
AB  - Analysis of the reduction in sizes of particles after chewing has been a standard
      method for assessing masticatory efficiency for over 40 years, but the sizing of
      particles with sieves is very time consuming. A rapid simple method of measuring
      chewed almond particle sizes by an optical scanning method has been developed and
      is described. The aim of this study is to validate the accuracy, repeatability
      and speed of the application of an optical scanning system in measuring chewed
      particles. To determine the accuracy, paper circles were measured and compared
      with the travelling microscope measurements. The effect of orientation of the
      images were assessed by measuring three irregular shaped pieces of paper and
      three different sized pieces of chewed almonds. Measurements were taken singly at
      18 degrees increments from 0-180 degrees orientations with each piece of paper.
      To assess the repeatability of measuring chewed particles, the particles from a
      single masticated almond washed with water and absolute alcohol were spread,
      separated and measured by the optical scanning system. The samples were then
      remeasured 10 times. The reproducibility of the method was investigated using
      three repeated masticatory tests for each subject in a group of 13 young dentate
      subjects. The speed of spreading the particles and of measurement was assessed.
      The absolute error range for a mean area of 31 mm2 was 2.85% to 7.32% with a mean
      of 3.86%. The relative accuracy of measurement was higher for larger particles
      but in no case was the standard deviation > 0.4 mm2.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7722748
TI  - Mean power frequency shift during fatigue and recovery in patients with
      craniomandibular disorders.
AB  - EMG spectral shifts of anterior temporal and medial masseter muscles were
      evaluated. Mean power frequency (MPF) shift during fatigue and recovery of 46
      healthy subjects and 46 patients with craniomandibular disorder were recorded at
      the beginning and the end of fatiguing clenching, then 3, 8, 13 and 18 min
      following the fatiguing clenching. The reference clenching force was 80% of each
      subject's maximal voluntary contraction (MVC). Recording was stopped when
      subjects felt pain or discomfort. Significance was found between the healthy
      group (N) and the diseases group (CMD) in the three following points: (i) the
      mean of MPF values of the masseter muscles at the end of fatiguing clenching;
      (ii) the recovery pattern of the temporal muscles; and (iii) MPF shift induced by
      fatiguing clenching. Our results therefore suggest that MPF reflects several
      aspects of craniomandibular disorders. Thus, measuring fatigue and recovery MPF
      could be useful in the screening of CMD.

PMID- 7722749
TI  - Prevalence of signs and symptoms of craniomandibular disorders and orofacial
      parafunction in 4-6-year-old African-American and Caucasian children.
AB  - Children, 4-6 years old, 153 Caucasian and 50 African-American, from a pre-school
      and kindergarten programme in a low income industrial area, who participated in a
      voluntary oral health examination, were questioned and examined for signs and
      symptoms of craniomandibular disorders (CMD) and of oral parafunctions. Most of
      the CMD signs and symptoms were mild. Eight per cent had recurrent (at least 1-2
      times per week) TMJ pain, and 5% had recurrent neck pain, African-American
      children more often than Caucasian children (P < 0.05). Seventeen per cent had
      recurrent headache. Three per cent had recurrent earache. Pain or tiredness in
      the jaws during chewing was reported by 25% of the children, more often by
      African-American than by Caucasian children (P < 0.001) and more often by girls
      than by boys (P < 0.05). Pain at jaw opening occurred in 10% of the children,
      more often in the African-American than in the Caucasian group (P < 0.001).
      Thirteen per cent of the children had problems in opening the mouth. Deviation
      during opening was observed in 17% and reduced opening in 2%. Reduced lateral
      movements, locking or luxation were not observed in any child. Palpation pain was
      found in the lateral TMJ area in 16%, in the posterior TMJ area in 25%, in the
      temporalis and masseter areas in 10%, and pain for all regions was found more
      often in the African-American than in the Caucasian children (P < 0.01). Thirty
      four per cent of the African-American, and 15% of the Caucasian children admitted
      to having ear noises (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722750
TI  - Association between CMD signs and symptoms, oral parafunctions, race and sex, in
      4-6-year-old African-American and Caucasian children.
AB  - The associations between oral parafunctions, signs and symptoms of
      craniomandibular disorders (CMD), race, and sex were analysed in recordings from
      203 4-6-year-old African-American and Caucasian children. Significant
      correlations were found between bruxism, nail biting, thumb sucking and most of
      the CMD signs and symptoms. There were also significant associations between most
      of the signs and symptoms and race, while significant association with sex was
      found only regarding headache, TMJ sounds and chewing pain. Significant
      associations were found between most CMD signs and TMJ sounds supporting the view
      that joint sound recordings have diagnostic value. There were also significant
      associations between the pain variables recorded by questionnaire and those
      recorded by palpation, which indicates that reliable data can be obtained by
      interviewing children as young as five. The results of this study support the
      concept that oral parafunctions have a significant role in the aetiology of CMD.
      The results also show that race and sex need to be considered when analysing the
      possible aetiological role of oral parafunctions in CMD. Longitudinal studies,
      beginning with low age groups are needed to better determine the role of
      childhood oral parafunctions in CMD aetiology.

PMID- 7722751
TI  - Should bone, soft-tissue, and joint injuries be treated with rest or activity?

PMID- 7722752
TI  - Rabbit medial collateral ligament scar weakness is associated with decreased
      collagen pyridinoline crosslink density.
AB  - This study was carried out to quantify the potential associations between
      material strength and both collagen concentration and pyridinoline collagen
      crosslink density in the healing medial collateral ligament of the rabbit and to
      compare these parameters with those of normal ligaments. The right hindlimbs of
      24 skeletally mature (12-month-old) New Zealand White rabbits were subjected to a
      standardized 4 mm midsubstance "gap" injury to the medial collateral ligament.
      The animals were killed in groups of six at postoperative intervals of 3, 6, 14,
      or 40 weeks, and the femur-medial collateral ligament-tibia complexes were
      mechanically tested in tension to failure. Subsequent to mechanical testing, the
      failure sites of the ligaments were assessed for concentrations of hydroxyproline
      and hydroxylysyl pyridinoline. Nine additional rabbits served as age-matched
      normal controls. In healing ligaments, normal collagen concentrations were
      reached in less than 14 weeks, but the hydroxylysyl pyridinoline crosslink
      densities remained low and were only 45% of the control values after 40 weeks of
      healing. Similarly, mechanical values remained much less than the controls.
      Linear regression analysis of data on scar tissue alone showed a moderately
      strong positive correlation between hydroxyproline concentration and material
      strength (r2 = 0.51, p = 0.0001) but no correlation between crosslink density and
      strength of scar tissue. A similar pattern of correlation was obtained between
      the elastic modulus of the scar tissue and the biochemical variables, but the r2
      values were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722753
TI  - Adhesiveness of human ligament fibroblasts to laminin.
AB  - The adhesiveness of fibroblasts from the human anterior cruciate and medial
      collateral ligaments to the laminin molecule was studied, with particular
      emphasis on the intrinsic differences between fibroblasts from the two ligaments.
      Cellular adhesion strength, adhesion area, laminin concentration, and seeding
      time were examined. Cell adhesion to laminin anchored with poly-D-lysine to a
      cleaned cover glass was measured with a micropipette micromanipulation system
      after seeding. The adhesion strength of fibroblasts from the anterior cruciate
      ligament to laminin was greater than and significantly different from that of
      fibroblasts from the medial collateral ligament, depending on the laminin
      concentration. Fibroblasts from the anterior cruciate ligament also exhibited an
      increase in adhesion strength, dependent on laminin concentration of as much as
      30 micrograms/ml, at which the laminin receptors were thought to be saturated.
      Fibroblasts from the medial collateral ligament did not show such an increase
      except at laminin concentrations of 5-10 micrograms/ml. There was no significant
      difference in adhesion area between fibroblasts from the two ligaments except
      after 45 minutes at a laminin concentration of 40 micrograms/ml. For both, the
      adhesion to laminin showed little correlation to seeding time during periods of
      as long as 60 minutes. Measurements of adhesion area also failed to show a
      significant correlation to seeding time for fibroblasts from either ligament at
      laminin concentrations of 20 and 40 micrograms/ml. Adhesion strength normalized
      by adhesion area had no correlation to seeding time.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7722754
TI  - Integrin display increases in the wounded rabbit medial collateral ligament but
      not the wounded anterior cruciate ligament.
AB  - The differential capacities of the anterior cruciate and medial collateral
      ligaments to heal may be related to differences in cellular function. This study
      tested the hypothesis that differential expression of integrins occurs in these
      ligaments after injury. The integrins are a family of cell surface receptors that
      mediate adhesion, migration, and other cellular functions critical to the healing
      of a wound. A similar complement and amount of the beta 1 subfamily of integrins
      are known to be present on the unperturbed anterior cruciate and medial
      collateral ligaments in humans and rabbits. A partial laceration was surgically
      created in these two ligaments in 12 anesthetized New Zealand White rabbits.
      Immunohistochemistry was performed on sections from the ligaments at 1, 3, 7, and
      10 days after injury, using monoclonal antibodies directed against the integrin
      subunits beta 1, alpha 5, alpha 6, and alpha v. Between 3 and 7 days, the wounded
      medial collateral ligament demonstrated a striking increase in staining for the
      beta 1, alpha 5, and alpha v subunits on the fibroblasts, within the repair site,
      and on capillary endothelium. Increased staining was most marked for the beta 1
      subunit and less marked for the alpha 5 and alpha v subunits. The alpha 6 subunit
      stained exclusively vascular structures within the healing medial collateral
      ligament. In marked contrast, the anterior cruciate ligament, which does not
      mount an effective repair response, demonstrated no comparable alteration of
      integrin expression from baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722755
TI  - Effect of growth factors on the proliferation of fibroblasts from the medial
      collateral and anterior cruciate ligaments.
AB  - Growth factors have been shown to stimulate fibroblast division and thus may
      influence ligament healing. We analyzed the effects of individual growth factors
      on the proliferation of fibroblasts from the medial collateral and anterior
      cruciate ligaments of the rabbit in vitro in order to identify growth factors
      that might enhance proliferation of fibroblasts and to compare the responses of
      the fibroblasts from the two ligaments to these growth factors. Through
      measurement of the uptake of [3H]-thymidine into DNA, fibroblasts from these
      ligaments that had been treated with epidermal growth factor and basic fibroblast
      growth factor were found to proliferate nearly eight times more than control
      fibroblasts. Additionally, the fibroblasts of both ligaments proliferated at
      similar rates when exposed to platelet-derived growth factor-AA, platelet-derived
      growth factor-BB, basic fibroblast growth factor, insulin-like growth factor-1,
      and interleukin-1-alpha. However, epidermal growth factor and transforming growth
      factor-beta caused the fibroblasts from the medial collateral ligament to
      proliferate at a rate 1.3-1.4 times greater than that of fibroblasts from the
      anterior cruciate ligament. The reverse was true with acidic fibroblast growth
      factor, which stimulated the fibroblasts from the anterior cruciate ligament to
      proliferate at a rate 1.3-1.6 times greater than that of fibroblasts from the
      medial collateral ligament. This study demonstrated that growth factors can
      stimulate cell division in ligaments and may be effective in enhancing ligament
      healing but that these differences were not great enough to explain fully the
      clinical differences observed between healing of the medial collateral and
      anterior cruciate ligaments.

PMID- 7722756
TI  - Immobilization of the knee joint alters the mechanical and ultrastructural
      properties of the rabbit anterior cruciate ligament.
AB  - The effects of immobilization of the knee joint on the mechanical and
      ultrastructural properties of the anterior cruciate ligament have not been well
      documented. Our goal was to determine these effects in a rabbit model and to
      assess the effect of knee flexion angle during immobilization. The knee joint was
      immobilized in either 170 degrees or 105 degrees of flexion, and new
      methodologies were utilized to determine the mechanical properties of the
      anterior cruciate ligament. In specimens from knees that had been immobilized,
      the cross-sectional area of the ligament was 74% of the control value. The stress
      strain curve was altered slightly, and the strain at failure increased 32-40%.
      The modulus and stress at failure did not decrease significantly. There was no
      significant difference between the mechanical properties of the knees immobilized
      at 170 degrees and 105 degrees of flexion. Histological and ultrastructural
      evaluation demonstrated changes in the shape and intracellular make-up of the
      fibroblasts from the ligament after immobilization. This cellular response may
      account for the alterations in the mechanical properties of the anterior cruciate
      ligament.

PMID- 7722757
TI  - Regional mitogenic response of the meniscus to platelet-derived growth factor
      (PDGF-AB).
AB  - Since meniscal healing is region-specific, we studied the regional (peripheral
      compared with central) response of meniscal explants to human, recombinant
      platelet-derived growth factor-AB. Meniscal explants from the hindlimbs of both
      knees of mature sheep were sectioned and were cultured with variable doses of
      human, recombinant platelet-derived growth factor-AB, and incorporation of [3H]
      thymidine was measured. The mitogenic response was measured at different times in
      culture (48 or 96 hours) and by location (lateral or medial). In the absence of
      the growth factor, the peripheral third of both menisci incorporated 10-fold more
      [3H]-thymidine on a weight basis than did the central two-thirds. Cellularity was
      equivalent in the two regions. Doses of less than 100 ng/ml of growth factor
      produced either no stimulation or a variable response. A dose of 100 ng/ml
      resulted in consistent, significant (p < 0.05) stimulation in all groups in the
      peripheral region, and a dose of 200 ng/ml provided more than a 2.5-fold
      increase. Multiple-factor analysis of variance demonstrated that there were no
      significant differences between experiments, times in culture, or menisci. The
      central region did not respond to stimulation with the growth factor at any of
      the doses tested. These data suggest that regional differences (peripheral
      compared with central) in responsiveness to human, recombinant platelet-derived
      growth factor-AB may reflect a different level of signal transduction machinery
      for growth factor receptors and distinct fibrobchondrocyte populations. These
      findings are consistent with the variable healing capacity of the meniscal
      regions in vivo and suggest a pharmacological means to promote the repair of the
      peripheral meniscal region.

PMID- 7722758
TI  - Dimensional growth and extracellular matrix accumulation by neonatal rat
      mandibular condyles in long-term culture.
AB  - Mandibular condyles in organ culture commonly have been used as a model system
      for examination of the factors that influence skeletal growth and development.
      The work reported here complements previously published histological studies by
      providing quantitative temporal information on growth and matrix accumulation.
      Condyles maintained for as long as 5 weeks in serum-free and 1% serum
      supplemented culture media were found to remain viable and metabolically active
      as demonstrated by continued dimensional growth as well as cell and matrix
      accumulation. Growth occurred by a combination of cell proliferation, matrix
      synthesis and accumulation, and cell hypertrophy (with the latter two mechanisms
      dominating). Increases in tissue volume correlated directly with increased
      glycosaminoglycan content; both increased 7-fold over 5 weeks. In comparison with
      serum-free culture, after 35 days in medium containing 1% serum,
      glycosaminoglycan content was 24% lower and collagen content was 36% higher,
      whereas dry weight, condyle length, and DNA content were not significantly
      different; in addition, histological observation suggested that, for samples
      cultured with serum, chondrogenic phenotype had been lost from some regions. The
      temporal behavior for all growth parameters exhibited a transient phase 1-2 weeks
      in duration followed by a steady-state period in which dimensions and tissue
      constituents or content increased at a constant or near constant rate. Comparison
      of the rates of incorporation of [35S]sulfate with glycosaminoglycan content in
      serum-free cultures suggests that the loss of glycosaminoglycan occurs only
      initially or is negligible; therefore, under these baseline conditions, cartilage
      glycosaminoglycan content reflects the biosynthetic rate. The high degree of
      reproducibility seen during steady-state growth suggests that these data provide
      reliable baseline information and further supports the notion that this model
      system is useful for investigation of the effects of specific physical factors on
      in vitro growth and development.

PMID- 7722759
TI  - Serum fractions and related agonists with calcium-mobilizing activity in the
      bovine growth plate chondrocyte.
AB  - Longitudinal growth of bone involves a complex sequence of cellular events in the
      cartilaginous epiphysis. Whole blood serum has been shown previously to be a
      potent stimulus to the cells of the growth plate, as demonstrated by its ability
      to activate the inositol phosphate-calcium second messenger system, resulting in
      a rise in intracellular Ca2+. By manipulating the preparation of serum to
      functionally separate it into its constituent parts, we have shown that the
      processes of platelet lysis and activation of the clotting cascade are
      responsible for the generation of factors that stimulate this signaling mechanism
      in isolated bovine growth plate chondrocytes. Through a subsequent trial of
      bioactive agents generated in these processes, we identified and partially
      characterized several novel agonists of growth plate chondrocytes:adenosine
      triphosphate and adenosine diphosphate, the purine energy substrates, and
      bradykinin, the bioactive peptide generated in a side reaction of the clotting
      cascade, each induces a rise in intracellular Ca2+ via release from intracellular
      ion stores. Additionally, the three distinct isoforms of platelet-derived growth
      factor (AA, AB, and BB), also released on platelet lysis, were compared with
      respect to their ability to stimulate the inositol phosphate-calcium second
      messenger system in growth plate chondrocytes.

PMID- 7722760
TI  - Structure of chondroitin sulfate on aggrecan isolated from bovine tibial and
      costochondral growth plates.
AB  - The structure of chondroitin sulfate on aggrecan isolated from the rib and
      proximal tibial growth plates of bovine fetuses was investigated, and the
      previously reported increase in the hydrodynamic size of chondroitin sulfate
      chains between the reserve and hypertrophic zones of the rib was confirmed in the
      tibial growth plate. Superose 6 gel chromatography, calibrated for chondroitin
      sulfate chain length by monosaccharide analysis, showed that the average
      molecular mass of chondroitin sulfate in the reserve and maturing zones of both
      growth plates was 21,600 and 30,400, respectively. Determination by capillary
      zone electrophoresis of the disaccharide composition of chains following
      chondroitinase digestion showed that delta Di-0S, delta Di-4S, and delta Di-6S
      together accounted for more than 98% of the disaccharides in the digests from all
      zones of both growth plates; delta disulfated and delta trisulfated disaccharides
      were not detected. Furthermore, this analysis revealed a gradient in chondroitin
      sulfate composition from the reserve to the hypertrophic zone, characterized by a
      marked increase in the content of delta Di-6S (from about 32% to about 52%) and a
      marked decrease in the content of delta Di-4S (from about 53% to about 35%).
      Moreover, this altered pattern of sulfation was detected on chains of all sizes
      in the hypertrophic zone, suggesting that a proportion of the reserve zone
      aggrecan might be removed and replaced with aggrecan rich in chondroitin-6
      sulfate synthesized during the proliferative and maturation stages of the
      resident chondrocytes. These data are discussed in relation to the biosynthetic
      mechanisms that control chondroitin sulfate chain length and sulfation on
      aggrecan and their modification during chondrocyte proliferation, maturation, and
      hypertrophy in the growth plate.

PMID- 7722761
TI  - Fiber composition and fiber transformations in neck muscles of patients with
      dysfunction of the cervical spine.
AB  - Biopsies of ventral neck muscles (sternocleidomastoid, omohyoid, and longus
      colli) and dorsal neck muscles (rectus capitis posterior major, obliquus capitis
      inferior, splenius capitis, and trapezius) were taken from 64 patients who
      underwent spondylodesis for cervical dysfunction of different etiologies. The
      muscle fibers were classified histochemically as type I, IIA, IIB, or IIC
      (transitional or intermediate fibers) according to the pH lability of their
      myofibrillar ATPase. Signs of muscle fiber transformations were observed in all
      muscles investigated, as evidenced by an increased relative amount of type-IIC
      fibers. The transformations occurred independently of (a) the type of muscle
      (i.e., more "postural" or more "phasic"), (b) the sex and age of the patient, (c)
      the type of condition, and (d) the presence of additional neurological deficits.
      Thus, the same pattern of muscular reaction was found in patients with rheumatoid
      arthritis as in patients with soft-tissue injuries of the neck (e.g., "whiplash
      injury"). In the ventral muscles and the obliquus capitis inferior, the
      occurrence of transformations correlated strongly with the duration of symptoms;
      in the ventral muscles the vast majority of transformations were encountered in
      patients with a shorter history of symptoms, whereas in the obliquus capitis
      inferior the reverse occurred. In the other dorsal muscles, no correlation with
      the duration of symptoms was found. Muscles in which transformations had ceased
      displayed, on average, a significantly higher percentage of fast type-IIB fibers
      than were found in muscles with ongoing transformations. This strongly indicates
      that the transformations proceeded in the direction from "slow oxidative" to
      "fast glycolytic."

PMID- 7722763
TI  - Texture correlation: a method for the measurement of detailed strain
      distributions within trabecular bone.
AB  - A new technique, termed texture correlation, is described for the measurement of
      displacement and strain patterns within samples of trabecular bone. Texture
      correlation is a modification of digital image correlation, a method for analysis
      of deformation in objects marked with random surface speckle. Instead of surface
      speckle, the trabecular pattern itself is used as a basis for correlation.
      Digitized contact radiographs of samples in unloaded and loaded states are
      compared by computer to determine displacements of a grid of points.
      Displacements are filtered with Savitsky-Golay polynomial-convolution filters to
      reduce noise, and then strain is calculated with finite element techniques. The
      method is conceptually similar to the manual measurement of surface markers but
      has numerous advantages: no marking of the sample is required, displacements are
      measured automatically by computer, measurement of thousands of displacements is
      practical, and filtering allows calculation of strain over small regions of the
      sample. The validity of the technique is demonstrated by comparison of strain
      patterns measured by texture correlation at low resolution with the same patterns
      measured by a surface marker technique in six samples of trabecular bone from a
      human femoral head. The results of texture correlation at full resolution then
      are presented to demonstrate the capabilities of the method.

PMID- 7722762
TI  - Clinical reproducibility of dual energy x-ray absorptiometry.
AB  - Dual energy x-ray absorptiometry is a technique advocated for the measurement of
      bone mass throughout the skeleton, and recently it has been used to measure
      changes in periprosthetic bone mass after joint replacement. The accuracy and
      precision of the method in clinical patient populations have not been firmly
      established. This study sought to establish the short-term reproducibility of
      measurements made with dual energy x-ray absorptiometry of multiple sites in a
      large sample of elderly patients with rheumatic disease. Reproducibility was
      assessed in the lumbar spine and in three femoral sites in 69 patients
      participating in a longitudinal clinical trial. In each patient, absorptiometry
      was performed twice in the same day at as many as five time points over a 2-year
      period. The mean (+/- SD) baseline bone density was 0.783 +/- 0.128 g/cm2 for the
      femoral neck and 1.015 +/- 0.218 g/cm2 for the lumbar spine. The correlations
      between the duplicate baseline measurements of the spine were excellent (r =
      0.9936, p < 0.001) and were stable over the 2-year period; the mean difference
      between the duplicate baseline measurements was 1.82 +/- 1.54% and the mean
      coefficient of variation was 1.29%. Measurements in the femur were much less
      precise; these values were 3.61 +/- 3.14% and 2.55% in the femoral neck, 3.66 +/-
      4.35% and 2.59% in the greater trochanter, and 5.28 +/- 5.61% and 3.73% in Ward's
      triangle. This study evaluated the short-term reproducibility of dual energy x
      ray absorptiometry in a clinical population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722764
TI  - Subchondral bone density in the human elbow assessed by computed tomography
      osteoabsorptiometry: a reflection of the loading history of the joint surfaces.
AB  - The functional adaptation of bone tissue to the mechanical stresses acting on it
      has been convincingly established. This association should apply as well to the
      subchondral bone, reflecting the long-term distribution of stress over the joint
      surfaces. Thirty-six specimens of the human elbow joint were investigated by
      computed tomography osteoabsorptiometry in order to assess the distribution of
      the subchondral mineralization. The distal surfaces usually were more highly
      mineralized than the proximal components of the joint, whereas the humeroulnar
      and the humeroradial parts exhibited a similar degree of mineralization. The
      fovea of the radial head always showed a central density maximum, and the
      trochlear notch usually presented a bicentric distribution pattern, with maxima
      beneath the ventral and dorsal regions of the articular surface. The different
      patterns of subchondral mineralization were shown to reflect the loading history
      of the overlying articular surfaces, which is determined mainly by geometrical
      factors. The flatter socket of the humeroradial joint leads to central load
      transmission, but the deeper socket of the humeroulnar joint will, by contrast,
      give rise to bicentric stress distribution.

PMID- 7722765
TI  - Reduction of patellofemoral contact forces following anterior displacement of the
      tibial tubercle.
AB  - Retropatellar pain often accompanies malalignment syndromes and frequently is
      attributed to excessive patellofemoral contact stresses. Elevation (anterior
      displacement) of the tibial tubercle has been recommended to relieve these
      conditions. The degree to which patellar contact forces are decreased and the
      extent to which elevation alters medial-lateral forces have not been studied
      directly. We performed anterior translation of the tibial tubercle in knees from
      cadavers and measured the effect on the magnitude of the three-dimensional
      patellofemoral contact force with use of a specially designed 6-degrees-of
      freedom force transducer, with the natural patellar articular surface in place.
      Measurements were made in nine knees (average age 67 years, range 46-92 years).
      The resultant contact force decreased linearly with increasing tubercle
      elevations of as much as 2.5 cm. The average reduction per centimeter of
      elevation was 17% of the force measured with no elevation. Elevation of the
      tubercle had an inconsistent effect on the medial-lateral component of the
      contact force. As the elevation was increased, six knees exhibited an increase in
      the medial-lateral component of the contact force acting medially on the knee and
      three knees exhibited a decrease in this force component. The results of this
      study show that, while elevation of the tubercle without medialization reduced
      the total contact force on the patella, the medial-lateral component of this
      force was altered in an unpredictable way.

PMID- 7722766
TI  - Contaminated fractures of the tibia: a comparison of treatment modalities in an
      animal model.
AB  - External fixation is the current standard treatment for skeletal stabilization of
      open tibial fractures, but intramedullary fixation techniques have become
      increasingly popular. The aim of this study was to compare, in an animal model,
      the susceptibility to infection of contaminated fractures stabilized with
      external fixation with that of contaminated fractures fixed with intramedullary
      locking nails with or without reaming. A unilateral osteotomy of the tibia was
      performed in 15 goats under general anesthesia. Each osteotomy was stabilized
      with either (a) a unilateral biplanar external fixator, (b) an 8 mm diameter
      intramedullary rod inserted without reaming of the medullary cavity, or (c) a 10
      mm diameter rod inserted after reaming. A standardized inoculum of Staphylococcus
      aureus, 10(3) colony forming units per milliliter, was placed at each osteotomy
      site on a piece of absorbable gelatin sponge, to simulate contamination of an
      open fracture. Antibiotics were not administered. The animals were allowed full
      activity after the procedure. Fourteen days postoperatively, the animals were
      killed, radiographs of the tibiae were taken, and the tibiae were harvested in a
      sterile manner. Multiple specimens for quantitative microbiological analysis were
      taken from the fracture site and from sites 3 cm distal and 6 cm proximal to the
      fracture. Additional specimens of bone were taken for histological study.
      Clinical, radiographic, and microbiological analysis demonstrated that, in this
      animal model, there were significantly fewer and less severe infections in
      fractures fixed with external fixation than in those fixed with an intramedullary
      nail with or without reaming. There was marked cortical necrosis in tibiae that
      had been fixed with nailing and reaming.

PMID- 7722767
TI  - Elastase activity, uninhibited by alpha 1-antitrypsin, in the periprosthetic
      connective matrix around loose total hip prostheses.
AB  - To clarify the proteolytic cascade in the loosening of total hip prostheses, the
      presence, tissue localization, and content of the serine proteinase, elastase,
      and its endogenous inhibitor, alpha 1-antitrypsin, were studied in periprosthetic
      tissues around 12 loose hip prostheses by immunohistochemistry,
      spectrophotometric enzyme assay, and immunoblot analysis, and the results were
      compared with those in control synovial tissue samples from eight knees.
      Increased numbers of elastase-immunoreactive cells and elevated elastase
      activity, inhibited by the addition of native alpha 1-antitrypsin, were observed
      both in the interface tissues between the bone and implants and in the
      pseudocapsular tissues from around loose hip prostheses. Elevated elastase
      activity, uninhibited by alpha 1-antitrypsin in situ and inhibited by the
      addition of native inhibitor, suggests a proteinase-inhibitor imbalance that
      contributes to the weakening of periprosthetic tissues and thus causes the
      loosening of hip prostheses.

PMID- 7722768
TI  - NH2-terminal sequence of novel pancreatic stone protein-related protein in human
      urine.
AB  - In a previous report, we detected the novel PSP-related protein in urine from a
      patient with diabetic nephropathy. This protein was different from PSP S1 and PSP
      S2-5 on the elution points of Mono S chromatography. To investigate the NH2
      terminal sequence, we purified this protein by reverse phase chromatography and
      performed amino acid analysis. The results showed that the NH2-terminal sequence
      of this protein was one residue (arginine) longer than that of PSP S1.

PMID- 7722769
TI  - Platelet indices in athletes performing a race in altitude environment.
AB  - Physical activity could modify platelet count and platelet indices. Previous
      reports showed modifications after exercise linked to type and duration of sports
      performances. The shortage of studies in this field stems from the crucial
      methodological problem of EDTA (ethylenediaminetetraacetic acid)-dependent, mean
      platelet volume modifications: the published data on platelets count and indices
      were obtained by using a light-scattering system without standardization of the
      period elapsed from drawing to measurement. We present a study of platelet
      indices performed in athletes participating in an "extreme" performance, a race
      of 30 km in altitude (6,700 m of ascents and descents), using standardized
      measurement by an aperture-impedance instrument transferred in the field. The
      platelet count and mean platelet volume significantly increased in athletes,
      whereas platelet distribution width decreased. The mean initial values were
      240.6*10(9)/L for platelet count, 8.79 fL for mean platelet volume, and 15.79%
      for platelet distribution width. The correspondent mean final values were
      288.4*10(9)/L, 9.14 fL, and 15.48%. The modifications of platelet count and
      indices were always in the physiological reference range. The entity and the
      rapidity of platelet count and indices modifications suggest that the more
      probable source of variation is the recruitment of noncirculating pools of mature
      platelets. Strenuous exercise does not show abnormal changes of platelet
      parameters.

PMID- 7722770
TI  - Racial differences in serum immunoglobulin levels: relationship to cigarette
      smoking, T-cell subsets, and soluble interleukin-2 receptors.
AB  - To investigate the influence of race, cigarette smoking, and immunologic
      parameters on serum immunoglobulins, we analyzed serum IgG, IgA, and IgM levels
      in 455 healthy adults. The study population ranged in age from 20 to 69 years,
      including 282 whites and 173 blacks, 181 never-smokers, 93 ex-smokers, and 181
      current smokers. Race and smoking were independently associated with alterations
      in serum IgG levels. Blacks had significantly higher IgG levels than whites
      (1,587 vs. 1,209 mg/dl; P < 0.001), and never smokers had significantly higher
      levels than current smokers (1,426 vs. 1,287 vs. mg/dl; P < 0.001). IgA and IgM
      levels were unrelated to race or smoking. Serum IgG was also found to be directly
      related to the proportion of HLA-DR+ cells and the level of soluble interleukin-2
      receptors (sIL-2R) and inversely related to the proportion of CD4+ cells.
      Investigation of this racial heterogeneity may provide insights into the
      pathogenesis of immunologic diseases that exhibit unexplained racial variation.

PMID- 7722771
TI  - Magnetophoresis: II. Quantification of iron and hemoglobin content at the single
      erythrocyte level.
AB  - The iron and hemoglobin content of individual erythrocytes was determined using a
      method based on parallel velocity measurements during magnetophoresis and
      gravitational sedimentation of individual erythrocytes in suspension. In previous
      publications we have suggested employing cell magnetophoresis, a biophysical
      phenomenon characterized by cell movement in a fluid under magnetic field
      influence, for cytometry. The paramagnetic ferric iron in methemoglobin is used
      as a magnetic label. The iron content is estimated from the magnetophoresis
      velocity, and hemoglobin content from the gravitational sedimentation velocity of
      erythrocytes. Blood samples are also analyzed in a Coulter counter to determine
      their mean corpuscular hemoglobin. The time course of the reaction of
      methemoglobin reduction is quantified at the single erythrocyte level. The
      methemoglobin content in individual erythrocytes is determined following the
      oxidation reaction. Erythrocytes from patients with normo-, hypo-, or
      hyperchromic anemia exhibit magnetophoresis and gravitational sedimentation
      velocities that correlate closely with mean corpuscular hemoglobin. We propose
      the utilization of magnetophoretic cytometry for detailed diagnostic studies at
      the single erythrocyte level. Furthermore, the magnetophoresis velocity to
      gravitational sedimentation velocity ratio is proposed as a standard value for
      comparative study of magnetically labeled cells in future investigations, as it
      was found to be constant and independent of hemoglobin content.

PMID- 7722772
TI  - Laboratory study on occult gastrointestinal bleedings: differential diagnostic
      method for the parallel study of intact and fragmented hemoglobin.
AB  - The authors produced various degradation products of human hemoglobin. With the
      aid of immune sera raised against native hemoglobin and their fragments, we
      examined the antigenicity of the intact molecule and fragments as well as the
      specificity and reactivity of the immune sera used. Since conventional guaiac
      type reactions make no distinction between the different hemoglobin molecules and
      the methods described in recent years' publications only with immune sera raised
      against native intact hemoglobin, the demonstration of occult fecal blood has not
      reached the desired rate of efficacy in clinical practice. The authors recommend
      the introduction of a simple differential diagnostic methods suitable for the
      parallel examination of intact and fragmented hemoglobin.

PMID- 7722773
TI  - Evaluation of recombinant Ro/SSA, La/SSB, Sm, and U1 RNP autoantigens in clinical
      diagnosis.
AB  - This study comprises an analysis of the diagnostic usefulness of Ro/SSA, La/SSB,
      Sm and U1 RNP autoantigens obtained by DNA recombinant technology. We studied the
      presence of these autoantibodies in 33 patients with systemic lupus erythematosus
      (SLE) and 30 normal individuals by enzyme-linked immunosorbent assay (ELISA)
      using recombinant autoantigens and by Western immunoblot with these same antigens
      obtained from natural sources (rabbit thymus and human spleen). The strength of
      agreement between results found with these two techniques was moderate in the
      case of anti-Ro/SSA (kappa = 0.474, P < 0.001) and anti-U1 RNP (kappa = 0.566. P
      < 0.001) antibodies and almost perfect in the case of anti-La/SSB (kappa = 0871,
      P < 0.001) and anti-Sm (kappa = 0.833, P < 0.001). Furthermore, analysis of the
      disagreement between the two techniques evidenced a measurement bias for anti
      Ro/SSA and anti-U1 RNP antibodies (Mc NEMAR'S statistic 13 and 11, respectively)
      whose direction, though difficult to define in the absence of a gold standard for
      such determinations, could be accounted for by the ELISA technique's greater
      tendency to produce positive results. Our conclusion is that the diagnostic
      usefulness of recombinant La/SSB and Sm autoantigens has been satisfactorily
      proven, whereas the case of the Ro/SSA and U1 RNP systems should be subject to
      further in-depth study of the autoepitopes recognised and the possible
      modifications which the latter might undergo as a result of their obtension from
      procariotic sources.

PMID- 7722774
TI  - A novel magnetic particle agglutination in microtiter plates for rapid detection
      of human T-lymphotropic virus type I antibody.
AB  - We have developed a novel magnetic particle agglutination (MPA) method for rapid
      detection of antibody to human T-lymphotropic virus type I (HTLV-I). This method
      is suitable for screening determination. The assay uses purified viral antigen
      coated on magnetic particles, which are novel artificial particles made of
      gelatin, arabic gum, and ferrite. MPA uses a special magnet and inclined plate
      holder. In MPA, the specimen is incubated with magnetic particles in the well;
      magnetic particles are then magnetically attracted to the bottom of the well.
      Then the plate is inclined and read by the naked eye. In a positive specimen,
      agglutination particles stay at the bottom of the well. On the other hand, non
      agglutination particles with negative sample run down the side of the well. The
      total assay time of MPA was estimated at 8 min/microtiter-plate. The results
      obtained by correlating MPA for the detection of HTLV-I antibody with other
      method emphasized the precision of MPA.

PMID- 7722775
TI  - Apolipoprotein E genotyping methods for the clinical laboratory.
AB  - To select the best method for detecting apolipoprotein E (apo E) genotypes
      determined by the three common alleles epsilon 2, epsilon 3 and epsilon 4, we
      compared the radiolabeled allele-specific oligonucleotide (ASO) probe assay and
      the nonisotopic restriction isotyping assay. Leukocytic DNA was extracted from
      the blood of 93 patients after which the region containing two mutation points
      coding amino acid residues 112 and 158 was amplified by using the polymerase
      chain reaction (PCR). Amplified DNA fragments were spotted on nylon membranes,
      then hybridized for the ASO probe assay. The amplified DNA fragments were also
      digested with restriction endonuclease Hhal, followed by polyacrylamide gel
      electrophoresis for the restriction isotyping assay. The apo E genotypes
      determined by both methods for every specimen studied were in complete agreement.
      Although the radiolabeled ASO probe method was 10 times more sensitive than
      restriction isotyping on polyacrylamide gel, the two were comparable in accuracy.
      Additionally, because it is simpler to perform, is less time consuming, and is
      less expensive, we conclude that the restriction isotyping assay is the more
      suitable of these two methods for use in a clinical laboratory.

PMID- 7722776
TI  - Autoantibodies against oxidized low density lipoprotein: a review of clinical
      findings and assay methodology.

PMID- 7722777
TI  - Stability of blood homocyst(e)ine under epidemiological field conditions.

PMID- 7722778
TI  - Decreased cytoplasmic immunoglobulin A production during Epstein-Barr virus
      immortalization on lymphocytes from patients with ataxia-telangiectasia.
AB  - Previously, we have reported significantly lower immunoglobulin (Ig) A production
      in supernatants of cultured lymphoblastoid cells using enzyme-linked
      immunosorbent assay from patients with ataxia-telangiectasia (AT) when compared
      to that of age- and sex-matched healthy individuals. Here, we further assess the
      degree of cytoplasmic Ig production in these cells and also analyze it during the
      early phase of Epstein-Barr virus immortalization. All classes of cytoplasmic
      IgM, IgG, and IgA productions were demonstrated in cells from healthy controls.
      In contrast, cells from patients with AT showed only cytoplasmic IgM and IgG with
      low or nondetectable levels of IgA during and after the immortalizing process.
      These results suggest B lymphocytes bearing IgA are functionally immature and/or
      defective in patients with AT.

PMID- 7722779
TI  - Candida albicans, the life and times of a pathogenic yeast.

PMID- 7722780
TI  - Changing taxonomic concepts and their impact on nomenclatural stability.

PMID- 7722781
TI  - Mechanisms of cell-mediated immunity in fungal infection.

PMID- 7722782
TI  - Animal ringworm--its aetiology, public health significance and control.

PMID- 7722783
TI  - Host cell-fungal cell interactions.

PMID- 7722784
TI  - The current role of Aspergillus and Penicillium in human and animal health.
AB  - Aspergillus and Penicillium are ubiquitous fungi, usually found as saprophytes.
      Only a few species are considered to be important in human or animal disease.
      However, many otherwise benign species are supreme opportunists and have been
      found increasingly as invaders of the immuno-compromised. This paper first
      describes with a broad brush modern approaches to the classification of these
      genera, the reasons behind some name changes and the effective forces now acting
      to stabilize names. Recent taxonomic schemes are described. The taxonomy of
      pathogenic Aspergillus and Penicillium species is outlined, the subgenera where
      pathogens occur identified, and the question of why particular species are
      pathogens addressed. The significance of Aspergillus and Penicillium in mammalian
      disease is heightened by their production of potent mycotoxins. The importance of
      Aspergillus flavus and aflatoxins as a cause of human death in parts of Africa
      and Asia and the impact of ochratoxins, produced by Penicillium verrucosum, on
      human and animal health in Europe will be emphasized. Possible mycotoxin
      ingestion from spores poses a further health threat.

PMID- 7722785
TI  - Mechanisms and clinical impact of antifungal drug resistance.

PMID- 7722786
TI  - Cytokines in the host response to mycotic agents.
AB  - In summary, different approaches have been taken to understand cytokine responses
      to different fungal infections. Singer-Vermes and co-investigators indirectly
      examined cytokine responses to paracoccidioidomycosis by studying the types of
      cellular and humoral immune responses that were induced in resistant and
      susceptible mouse strains. Their results implicated Th1 cell responses in the
      resistant mouse strain and Th2 cell responses in the mouse strain susceptible to
      paracoccidioidomycosis. By measuring cytokine production and through cytokine
      depletion experiments, Wu-Hsieh showed that besides IFN gamma, TNF alpha was
      important in host defences against the intracellular pathogen, H. capsulatum.
      Both cytokines play important roles in the regulation of other cytokines. In
      histoplasmosis, the dynamics of the complex interactions amongst cytokines govern
      the efficiency of host clearance of the fungus from tissues. Ferrante and
      collaborators, examining TNF alpha and TNF alpha receptors on neutrophils
      presented data showing that TNF alpha plays an important role in the activation
      of neutrophils for anti-Candida activity. Through the detection of cytokine mRNAs
      with RT-PCR, Moser and co-workers found that cytokine mRNAs of macrophage origin
      were produced preferentially in the lungs of mice infected with Histoplasma or
      Blastomyces. A great challenge still lies ahead of us. It is well understood that
      the interactions of cytokines are extremely complex at the levels of the
      induction and expression of the immune responses as well as on effects on natural
      cellular defences. Work accomplished thus far has laid the ground work for future
      studies in the effort to dissect host cytokine responses and to understand the
      roles of cytokines in protection against fungal infections.

PMID- 7722787
TI  - Practical mycology for low budget laboratories.

PMID- 7722788
TI  - Recent advances in the biology of Pneumocystis carinii.

PMID- 7722789
TI  - Pathogenesis of invasive candidiasis.

PMID- 7722790
TI  - Immunodiagnosis of invasive fungal infections.

PMID- 7722791
TI  - Immunomodulation in mycoses.

PMID- 7722792
TI  - Antifungal drug susceptibility testing.

PMID- 7722793
TI  - Household hyphomycetes and other indoor fungi.

PMID- 7722794
TI  - Molecular approaches to identify novel targets for future development of
      antifungal agents.

PMID- 7722795
TI  - Recent developments in the diagnosis and treatment of subcutaneous mycoses.

PMID- 7722796
TI  - Developments in hyalohyphomycosis and phaeohyphomycosis.

PMID- 7722797
TI  - Recent advances in the epidemiology, prevention and treatment of invasive fungal
      infections in neutropenic patients.

PMID- 7722798
TI  - Molecular mycology: DNA probes and applications of PCR technology.

PMID- 7722799
TI  - Malassezia and Trichosporon: two emerging pathogenic basidiomycetous yeast-like
      fungi.

PMID- 7722800
TI  - Stress, immunity and mycotic diseases.

PMID- 7722801
TI  - Molecular biology of Cryptococcus neoformans and therapy of cryptococcosis.

PMID- 7722802
TI  - Molecular biological and biochemical aspects of fungal dimorphism.

PMID- 7722803
TI  - Mycoses in AIDS patients.

PMID- 7722804
TI  - Potential molecular targets of metabolic pathways.

PMID- 7722805
TI  - The miracle at the Radcliffe Infirmary. How a son of Adelaide and a mould changed
      the world.

PMID- 7722806
TI  - Pathogenesis of superficial mycoses.

PMID- 7722807
TI  - Pathophysiology of congenital diaphragmatic hernia. VIII: Inhaled nitric oxide
      requires exogenous surfactant therapy in the lamb model of congenital
      diaphragmatic hernia.
AB  - The pathophysiology of the lamb model of congenital diaphragmatic hernia (CDH)
      involves pulmonary hypoplasia, pulmonary hypertension, and surfactant deficiency.
      Inhaled nitric oxide (NO) is a highly selective pulmonary vasodilator. The aim of
      this study was to determine the effects of inhaled NO on pulmonary gas exchange,
      acid-base balance, and pulmonary pressures in a lamb model of CDH with or without
      exogenous surfactant therapy. At the gestational age of 78 days (full term, 145
      days) 11 lamb fetuses had a diaphragmatic hernia created via a left thoracotomy
      and then were allowed to continue development in utero. After cesarean section,
      performed at term, six lambs received exogenous surfactant therapy (50 mg/kg,
      Infasurf) and five served as controls. All animals were pressure-ventilated for
      30 minutes and then received 80 ppm of inhaled NO at an F1O2 of .9 for a 10
      minute interval. Compared with the control lambs, the lambs with exogenous
      surfactant therapy had higher pH (7.17 +/- .06 v 6.96 +/- .07; P < .05), lower
      PCO2 (73 +/- 8 v 122 +/- 20, p < .05), and higher PO2 (153 +/- 38 v 50 +/- 23; P
      < .05). In control CDH lambs (without surfactant), inhaled NO did not improve pH,
      PCO2, or PO2, or decrease pulmonary artery pressure. In CDH lambs given exogenous
      surfactant, NO decreased pulmonary artery pressures (42 +/- 4 v 53 +/- 5; P <
      .005) and further improved PCO2 and PO2. NO also made the difference between
      pulmonary and systemic artery pressures more negative in the surfactant-treated
      lambs (-15 +/- 4 v -2.3 +/- 2.4; P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722808
TI  - Outcome for infants with congenital diaphragmatic hernia requiring extracorporeal
      membrane oxygenation: the first year.
AB  - Congenital diaphragmatic hernia (CDH) has been associated with a high mortality
      rate. The purposes of this study were to determine the impact of extracorporeal
      membrane oxygenation (ECMO) on the survival of infants with CDH and to document
      the sequelae and 1-year neurodevelopmental outcome for CDH infants who required
      ECMO. Thirty neonates with CDH were admitted between May 7, 1990 and October 1,
      1992. Twenty required ECMO and were enrolled in our neonatal follow-up program.
      Information about the infants' neonatal course was obtained from chart review,
      and the infants were seen at 3, 6, and 12 months of age for medical and
      neurodevelopmental follow-up. Primary diaphragmatic repair was performed in 13
      infants. Five required Goretex graft reconstruction (GGR), and two did not have
      repair. Sixteen (80%) of the 20 infants who required ECMO survived. The overall
      survival rate increased from 31% (10 of 32) in the 5 years previous to the start
      of the ECMO program to 63% (19 of 30) since then (P = .01). The most common
      sequelae noted by the time of discharge included gastroesophageal reflux (GER;
      81%), the need for tube feeding (69%), and chronic lung disease (CLD; 62%). At 1
      year of age, mean cognitive skills were average (87 +/- 23) and motor skills were
      borderline (75 +/- 24) according to the Bayley Scales of Infant Development.
      Hypotonia was present in 10 of 13 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722809
TI  - Treatment of nevi aranei with the pulsed tunable dye laser at 585 nm.
AB  - One hundred children aged < or = 12 years with spider nevi of the face have been
      treated with the SPTL-1 laser. The laser emits pulsed light at a wavelength of
      585 nm, with a pulse duration of 450 microseconds. The series included 37 boys
      and 63 girls. Patients whose spider nevi were previously treated with other
      methods were excluded. In 97 cases the lesions were completely removed, but 29%
      of them required more than one treatment session. Six months later, two patients
      had mild recurrence of the nevi, which required further treatment. No signs of
      scarring or of textural or permanent pigmentary changes have been noted.

PMID- 7722810
TI  - The sea, stingers, and surgeons: the surgeon's role in prevention, first aid, and
      management of marine envenomations.
AB  - Marine envenomations are the statistical price that humankind pays for intruding
      into the aquatic domain. Individual risk can be reduced by knowledge and
      prudence. If envenomations do occur, lives can be saved, complications prevented,
      and convalescence facilitated by knowledge of and interest in these fascinating
      creatures of the sea.

PMID- 7722811
TI  - Injury to the common iliac artery during suction rectal biopsy.
AB  - A case of injury to the common iliac artery during suction rectal biopsy is
      described. Factors that might influence the incidence of complications after
      suction rectal biopsy are considered. Suction rectal biopsy, although invaluable
      in establishing the diagnosis of Hirschsprung's disease, is a potentially
      dangerous technique and should not be delegated to an inexperienced operator. In
      neonates it is unwise to take biopsy specimens more than 4 cm from the anal
      verge. A posterior approach is likely to be safer than an anterior or lateral
      one.

PMID- 7722812
TI  - Anal agenesis associated with rectal atresia.
AB  - The authors report an unusual case of anal agenesis associated with rectal
      atresia. Such an anomaly has been reported only once before. Coincidentally, this
      patient also had a rarely encountered skeletal anomaly--unilateral cleft foot.

PMID- 7722813
TI  - Unconventional treatment of neuroenteric cyst in a newborn.
AB  - Neuroenteric cysts are uncommon congenital malformations that can require early
      surgical treatment. The authors report on an unusual treatment of a very large
      neuroenteric cyst that involved most of the small bowel and extended into the
      chest. A 1-day-old boy was admitted because of abdominal distension. The prenatal
      ultrasound results at 8 and 36 weeks had been normal. Examination showed right
      upper quadrant fullness and mild respiratory distress. A malformed sternum and
      asymmetric upper thoracic vertebra were seen on the initial x-rays. The
      possibility of a midthoracic right paravertebral mass was raised. Abdominal
      ultrasound findings were consistent with a large bowel duplication cyst.
      Laboratory results were all normal except the bilirubin level, which was (59
      mmol/L). During laparotomy, the second part of the duodenum was found to enter a
      dilated cyst, and the terminal ileum arose from the cyst. The total length of the
      intact small bowel was 20 cm including a competent ileocecal valve. The site of
      the biliary duct entering the cyst was not clear. The surgical procedure involved
      partial resection of the anterior wall of the cyst, creation of an enteric tube
      from the posterior cyst wall to communicate between the duodenum and the ileum,
      and addition of another 25 cm of length to the small bowel. An enterocutaneous
      fistula was created with the proximal portion of the cyst because the site of the
      papilla of Vater was suspected to enter this part of the cyst. A postoperative
      HIDA scan showed good uptake with no excretion into the gut or the proximal
      pouch.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722814
TI  - Malignant hemangioendothelioma presenting as omental masses in a child.
AB  - Malignant hemangioendothelioma is an uncommon lesion of the omentum in children.
      Multiple foci of malignant hemangioendothelioma is even more rare in the omentum.
      In the present case, a computed tomography scan of the abdomen showed multiple
      enhanced nodular lesions. To our knowledge, this is the first report of this
      tumor occurring in a child.

PMID- 7722815
TI  - Mesenteric teratoma in an 8-month-old girl.
AB  - The authors report the case of a solid, mature teratoma of the mesentery
      occurring in an 8-month-old girl. The tumor was enucleated from the ileocecal
      mesentery. Histologically the tumor included all three embryonal layers. This is
      the youngest patient reported to have mesenteric teratoma.

PMID- 7722816
TI  - Resection of the inferior vena cava for recurrent Wilms' tumor.
AB  - Wilms' tumor is one of the most common solid tumors of childhood. Approximately
      500 cases occur annually in the United States, and the overall incidence is 0.8
      per 100,000 children per year. Direct involvement of the inferior vena cava
      occurs in 5% to 10% of cases. The National Wilms' Tumor Study (NWTS), an
      intergroup cooperative clinical trial, indicates that aggressive primary surgical
      management combined with chemo-radiation therapy improves (with respect to both
      survival and recurrence) the long-term prognosis for children who have extrarenal
      involvement. In addition, aggressive surgical resection may further improve the
      survival rate for patients with recurrent Wilms' tumor after initial multimodal
      therapy.

PMID- 7722817
TI  - Congenital segmental giant megaureter.
AB  - A case of congenital segmental giant megaureter is reported. The patient
      presented with an asymptomatic abdominal mass resulting from the megaureter. A
      mildly hydronephrotic ipsilateral kidney was palpable as a separate mass. The
      ureter proximal and distal to the dilated segment showed normal peristaltic
      activity. Treatment consisted of excision of the dilated segment, with end-to-end
      ureteric anastomosis.

PMID- 7722818
TI  - Bladder, urethral, and vaginal duplication.
AB  - The authors report on an infant girl with bladder duplication. There was complete
      duplication of the bladder, urethra, uterus, and vagina, associated with a
      urogenital sinus and an anterior ectopic anus. Despite careful attempts at
      examination, endoscopy, and organ imaging, the anatomy was not completely defined
      before surgical exploration. A satisfactory cosmetic result and functional lower
      genitourinary tract has been obtained.

PMID- 7722819
TI  - Pyomyositis in an adolescent female athlete.
AB  - A case of pyomyositis in a healthy 13-year-old female volleyball player is
      presented and discussed. This case is unusual because, historically, pyomyositis
      has been more common in males, especially those who participate in strenuous
      physical activity. However, competitive sports and vigorous exercise programs are
      becoming more widely available to young females. Therefore, a relative increase
      in the number of adolescent women with pyomyositis can be expected.

PMID- 7722820
TI  - Diaphragmatic agenesis as a distinct clinical entity.
AB  - Anatomically, diaphragmatic agenesis (DA) is the most extreme form of congenital
      diaphragmatic defect, but clinically it has not been defined separately from
      Bochdalek's hernia (BH). Between 1986 and 1992, the authors treated 55 neonates
      who had diaphragmatic defects. Forty-eight of these cases presented within 24
      hours of birth. Seventeen of these neonates (35.4%) were found to have DA; the
      other 31 (64.6%) had BH. There were no significant differences in maternal age,
      gestational age, gender ratio, birth weight, and incidence of coexisting
      congenital anomalies between the two groups. However, neonates with DA differed
      significantly from those with BH with respect to incidence of antenatal diagnosis
      (76.4% v 12.5%, P = .0004), mean Apgar scores at 1 (4.1 +/- 2.0 v 5.7 +/- 2.3; P
      = .034) and 5 (5.5 +/- 2.7 v 7.6 +/- 2.2; P = .016) minutes, mean duration of
      preoperative stabilization (2.8 +/- 2.0 v 2.1 +/- 1.9 days; P = .044), and
      postoperative respiratory support (27.7 +/- 13.6 v 9.3 +/- 8.0 days; P = .002).
      Complications occurred in all seven DA survivors (100%) and in only four (19.0%)
      of the 21 BH survivors (P = .0008). The long-term survival rate was significantly
      lower for neonates with DA (29.4% v 64.5%; P = .04). Diaphragmatic agenesis is a
      distinct clinical entity; its unique short- and long-term problems require
      careful management.

PMID- 7722821
TI  - Experience with abdominal wall closure for patients with congenital diaphragmatic
      hernia repaired on ECMO.
AB  - Congenital diaphragmatic hernia (CDH) and its attendant lack of abdominal domain
      can create major technical challenges with respect to diaphragmatic and abdominal
      wall reconstruction, especially in seriously ill infants who require
      extracorporeal membrane oxygenation (ECMO). The authors reviewed the medical
      records of all infants with CDH repaired on ECMO at their institution (group 1,
      15 patients), and compared them with infants having CDH repair before ECMO (group
      2, 20 patients) and with those who had CDH repair but did not require ECMO (group
      3, 15 patients). Thirty-seven of 50 patients survived (74%): 10 in group 1, 12 in
      group 2, and all 15 in group 3. There was a statistically significant difference
      (P < .001) with respect to the requirement of a polytetrafluoroethylene (PTFE)
      diaphragmatic patch for patients in group 1 versus those in both groups 2 and 3.
      There was also a significant difference in the number of patients in whom the
      abdomen could not be closed (P < .001 for group 1 v groups 2 and 3). Infants who
      require ECMO before CDH repair are more likely to have large diaphragmatic
      defects that require prosthetic reconstruction, and abdominal wall closure
      problems resulting from loss of abdominal domain, which further complicate the
      management of the physiological derangements from pulmonary hypoplasia and
      persistent pulmonary hypertension.

PMID- 7722822
TI  - Is early fascial closure necessary for omphalocele and gastroschisis?
AB  - Before the introduction of the "silo" for gastroschisis, the main goal of surgery
      was to cover the defect with skin. Since the silo has been used, the goals have
      been (1) to cover the defect with SILASTIC sheets and return the extraabdominal
      contents to the abdominal cavity by progressive plication of the silo and (2) to
      eventually close the defect by fascia-to-fascia approximation, before 1 month of
      age. In many series, early definitive abdominal wall closure resulted in
      mortality rates of 10% to 30%, usually because of bowel necrosis and resulting
      sepsis. At the author's institution, 20 newborns with large omphaloceles or
      gastroschisis have been treated, and fascial closure was obtained by the second
      week in 10 infants. In ten babies it was impossible to obtain early fascial
      closure without tension, and these children were managed differently. A
      nonaggressive two-stage approach was used, in which the goals were (1) early
      return of contents to the abdominal cavity and (2) only skin and granulation
      coverage of the defect (without aiming for early fascial closure or partial
      fascial closure) with a small central SILASTIC patch. Stage 1 is reduction of
      abdominal contents to the abdomen, through plication of the silo, over a 9 to 14
      day period. Stage 2 is removal of the silo and closure of the ventral abdominal
      wall defect using a SILASTIC patch to close most of the defect, after
      approximating fascia in the superior and inferior portions. If the skin cannot be
      closed, the patch usually separates in 14 to 21 days, the pellicle remaining
      becomes completely epithelialized in 1 to 2 months, and further surgery has not
      been necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722823
TI  - Orogastric magnet removal of ingested disc batteries.
AB  - Ingestion of disc batteries by infants and small children is an increasing
      problem. Batteries that remain in the stomach can corrode and damage mucosa
      and/or produce poisoning. Between 1989 and 1992, 37 children who had swallowed a
      total of 46 disc batteries presented to the Royal Hospital for Sick Children,
      Edinburgh, and were referred for battery removal by use of an orogastric magnet
      under fluoroscopy. Thirty-nine batteries were removed successfully (without
      anesthesia) from 32 children, using a magnet attached to an orogastric tube. In
      three cases the battery had passed into the small bowel. In one case, magnet
      extraction failed, but the two batteries the child had ingested subsequently
      passed into the small bowel. In two cases the patients refused to swallow the
      tube. In one of these cases the battery was removed successfully by the magnet,
      with the patient under general anesthesia; in the other it passed spontaneously
      into the small bowel. The authors conclude that orogastric magnet removal is a
      minimally invasive, well-tolerated method of removing ingested disc batteries.

PMID- 7722824
TI  - Cardiorespiratory changes in children during laparoscopy.
AB  - The authors prospectively examined the cardiorespiratory changes during brief
      laparoscopy (less than 15 minutes) in children. Intraoperative ventilatory
      management included a tidal volume of 12 mL/kg, with the rate adjusted to achieve
      an end-tidal CO2 (PETCO2) of 30 to 35 mm Hg. The initial rate and tidal volume
      were not changed during the procedure. Baseline measurements of heart rate, blood
      pressure, peak inflating pressure (PIP), PETCO2, and oxygen saturation were
      recorded every minute for 5 minutes before the start of the laparoscopic
      procedure, and every minute during the laparoscopic procedure. Fifty-five
      patients were enrolled in the study (age range, 1 month to 7 years; weight range,
      5.2 to 31 kg). PIP increased from the baseline value of 20 +/- 2.5 to 23 +/- 3.2
      cm H2O (P < .01) during laparoscopy. The increase in PIP was 5 or more in six
      patients, with a maximum of 7. PETCO2 increased from the baseline value of 32 +/-
      3.1 to 35 +/- 4.8 mm Hg (P < .01). The PETCO2 returned to baseline within 10
      minutes after completion of the laparoscopy. No increase in ventilatory
      parameters was required during the brief laparoscopic procedure.

PMID- 7722825
TI  - Early experience with laparoscopic pyloromyotomy for infantile hypertrophic
      pyloric stenosis.
AB  - The authors report on 37 infants with infantile hypertrophic pyloric stenosis who
      underwent successful laparoscopic pyloromyotomy. The average age was 6 weeks and
      average weight was 4.5 kg. Three 4-mm ports were used in each procedure. The
      average operating time was 29 minutes (range, 7 to 60 minutes). Feeding was begun
      an average of 5.2 hours (range, 3 to 12 hours) postoperatively, and the average
      time of discharge was 28 hours (range, 16 to 52 hours) postoperatively. There
      were no technical failures. One patient had minor surgical emphysema, which
      resolved spontaneously. Laparoscopic pyloromyotomy can be safe and successful in
      infants with hypertrophic pyloric stenosis.

PMID- 7722826
TI  - Laparoscopic-assisted orchidopexy: a new approach to the impalpable testis.
AB  - A new technique for a single-stage laparoscopic mobilization and fixation of
      impalpable testes is described. It offers the advantages of minimally invasive
      surgery and keeps other options available, including a two-stage procedure. Early
      results are encouraging, and a multicenter trial is necessary for further
      evaluation.

PMID- 7722827
TI  - Laparoscopic approach to surgical management of ovarian cysts in the newborn.
AB  - With the improvement of imaging techniques as well as the trend toward routine
      antenatal ultrasound scanning, the intrauterine diagnosis of fetal ovarian cysts
      is encountered more frequently. The authors describe the laparoscopic approach to
      the management of ovarian cysts. This approach is tolerated well by infants, and
      it may overcome the controversy between conservative and early surgical
      management by facilitating the subtle transition from diagnostic to therapeutic
      means, with salvation of the ovary whenever possible.

PMID- 7722828
TI  - Hemangioendothelioma of the liver in infants.
AB  - Hemangioendotheliomas are the most common type of hepatic vascular tumors that
      present in infancy. Eleven infants (nine boys, two girls) were referred for
      definitive management from 1970 through 1990. Ten were symptomatic, and the
      majority required intensive medical therapy because of cardiac failure. All were
      treated surgically. Three underwent partial hepatectomy for unilobar disease, and
      eight had ligation of the hepatic artery because of bilobar disease. There were
      two deaths (18%) in the early part of the series. Ligation of the hepatic artery
      was completely successful in controlling cardiac failure in six infants and was
      partially successful in one. There are two surgical options for treating
      symptomatic hepatic hemangioendotheliomata in infancy. Bilobar multifocal disease
      can be treated successfully by ligation of the hepatic artery; if localized,
      hemangioendothelioma can be resected, with rapid control of symptoms.

PMID- 7722829
TI  - Prevention of biliary cirrhosis following hepatic arterial thrombosis after liver
      transplantation in children by using ursodeoxycholic acid.
AB  - Hepatic artery thrombosis (HAT) after liver transplantation is a severe
      complication that often requires retransplantation. The authors have adopted a
      different approach, aimed at treating the perioperative HAT complications
      aggressively and early, with ursodeoxycholic acid (UDCA), to try to preserve the
      original graft. Eighty-six liver transplants were performed in 73 children (age
      range, 4.5 months to 17.5 years; median, 2.6 years). HAT occurred eight times, in
      seven patients (9.3%). Patients with HAT were significantly younger and smaller
      (mean age, 0.8 +/- 0.4 v 4.8 +/- 5.3 years; P < .02; mean weight, 7.4 +/- 0.8 v
      18.7 +/- 16.2 kg; P < .05). The incidence of HAT varied significantly according
      to the method of arterial reconstruction used: 4 of 16 (25%) when a donor iliac
      artery interposition graft to the aorta was used, 4 of 61 (6.6%) when the native
      hepatic artery was used, and 0 of 9 when the donor celiac axis was anastomosed
      directly to the aorta (P < .05). The incidence of HAT was not significantly
      different when reduced-size grafts were used. Early retransplantation was
      performed in three of the eight patients; two survived. All other patients were
      treated for 4 to 6 weeks with broad-spectrum antibiotics and amphotericin. Five
      patients were treated with UDCA, three immediately after the acute event and two
      after 4 and 6 months (respectively) post-HAT. The patients who had UDCA
      immediately post-HAT had histologically normal liver biopsy specimens. Results of
      liver function tests have been normal. One of these patients required
      transhepatic stenting of a common bile duct stricture for several
      months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722830
TI  - Reduced-size grafts--the solution for hepatic artery thrombosis after pediatric
      liver transplantation?
AB  - Reduced-size liver grafts (RSG) were developed to alleviate the donor shortage
      for pediatric patients, particularly those requiring emergency transplantation.
      In theory, the large size of the hepatic artery available for anastomosis from
      RSG, as opposed to whole pediatric grafts, is less likely to lead to hepatic
      artery thrombosis (HAT). Therefore, the authors reviewed their experience with
      HAT, comparing RSG and whole-liver grafts in pediatric patients undergoing
      emergency liver transplantation. Despite the severity of illness of the
      recipients (UNOS status IV), and the intrinsic damage to the graft during
      reduction, HAT was not seen after RSG for emergency pediatric transplantation. In
      contrast, 29% of pediatric recipients who received whole grafts for emergency
      transplantation had HAT. RSG is a safe alternative to whole-liver grafts for
      pediatric liver transplantation, and may reduce the incidence of HAT.

PMID- 7722831
TI  - Human hepatocyte isolation and transplantation into an athymic rat, using
      prevascularized cell polymer constructs.
AB  - Human hepatocyte viability and function in vivo in an athymic rat was assessed
      after transplantation on prevascularized polymer constructs with hepatotrophic
      stimulation. Sixteen liver biopsy specimens, weighing 5 to 12 g, were obtained
      from the New England Organ Bank and from the operating room after liver
      resection. In the laboratory they were catheterized and perfused to obtain liver
      cell suspensions. From eight of the 16 cell suspensions, only in vitro studies
      were performed. They showed 40% cell attachment 24 hours after initial cell
      plating. For patients aged 2, 35, and 60 years, they showed a 20% increase, a 1%
      decrease, and a 57% decrease (respectively) in cell number from day 2 to day 4,
      after cell plating. Eight cell suspensions were transplanted into athymic rats.
      On sections examined histologically, implanted hepatocytes were seen within the
      fibroblast ingrowth, in the space of the polymer device, until day 21 after cell
      injection. On day 9 after hepatocyte injection, reorganized hepatic parenchyma
      was seen on the tissue section. Implanted hepatocyte areas, quantitated through
      morphometric analysis on days 0, 3, and 7, showed a 36% increase in engraftment 3
      days after injection, and a 42% decrease 7 days after injection. At the same time
      points, immunoperoxidase staining visualized intracellular albumin, which was
      specific for the implanted hepatocytes. In conclusion, the authors demonstrated
      the feasibility of their technique (prevascularized polymer device with
      hepatotrophic stimulation), using human hepatocytes. Further studies are
      underway, before implementation of human clinical trials.

PMID- 7722832
TI  - Cholelithiasis in pediatric cardiac transplant patients on cyclosporine.
AB  - From June 1984 to June 1993, symptomatic chlolethiasis was observed in six (6.7%)
      of 90 cases of pediatric heart or heart-lung transplants at the author's
      institution. The incidence of cholelithiasis for all children under 16 years of
      age is estimated to be less than 1%. Previously, information on cholelithiasis in
      pediatric transplant patients on cyclosporine therapy had been limited. Studies
      concerning the incidence of gallstones in adult kidney and cardiac transplant
      patients have shown that there is an increase associated with cyclosporine,
      possibly related to elevated levels and hepatoxicity. Five patients underwent
      uneventful cholecystectomy. There was only one death, which occurred after
      emergency cholecysostomy tube placement for biliary sepsis. If indicated, biliary
      tract surgery can be performed safely in cardiac transplant patients. The authors
      report on their experience with symptomatic cholelithiasis in pediatric cardiac
      transplant patients and review the current literature on the hepatotoxic effects
      of cyclosporine.

PMID- 7722833
TI  - The role of endoscopic retrograde cholangiopancreatography in the management of
      choledochal cysts in children.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) was performed in eight
      consecutively treated patients with choledochal cyst to assess its technical
      feasibility and complications. Satisfactory visualization of the complete anatomy
      of the biliary tract was possible in seven patients. Four patients had a type IV
      choledochal cyst and three had type I. In one patient, the procedure showed a
      congenital web in the lower end of the common bile duct; in another, there was
      complete membranous block of the lower end of the common bile duct. The findings
      of ERCP and intraoperative cholangiography were concordant for six patients. Only
      one patient had exacerbation of preexisting cholangitis. The authors conclude
      that ERCP is an essential investigative method in the management of choledochal
      cysts in children.

PMID- 7722834
TI  - The Malone antegrade continence enema.
AB  - The previously reported Malone antegrade continence enema (MACE) was used in 21
      children for intractable fecal incontinence or constipation. Twelve are
      completely clean, and three are much improved (71% success rate). However, only
      four of the 21 have not had some type of complication, either minor or major.
      Five of the 21 now have a colostomy, and one has abandoned the procedure.

PMID- 7722835
TI  - Angiodysplasia of the colon in children.
AB  - Angiodysplasia of the colon as a cause of lower intestinal bleeding is diagnosed
      frequently in the elderly, with defined clinical characteristics. In the
      pediatric population there is little experience; only six cases have been
      reported. The present study evaluates the clinical, radiological, and surgical
      aspects of nine children with angiodysplasia of the colon who were treated at the
      National Institute of Pediatrics in Mexico City between 1970 and 1993. The mean
      age of clinical onset was 2.3 years. In six patients, symptoms appeared before
      the first year of life. Lower intestinal bleeding and severe anemia were present
      in all cases. The diagnosis and localization of the lesions were established by
      selective visceral angiography. Six patients were treated by operative resection
      of the affected colonic segments. For four patients with lesions in the rectum
      and sigmoid, a Swenson pull-through was performed. In one patient the lesion was
      recurrent because of incomplete resection. Follow-up ranges from 8 months to 4
      years; all patients have had normal hemoglobin levels and negative stool results.
      Unlike in the elderly and the cases reported in the literature, the left
      hemicolon was the most frequently involved area.

PMID- 7722837
TI  - Congenital fibrosarcoma masquerading as lymphatic malformation: report of two
      cases.
AB  - Two infants presented with a congenital cervicothoracic mass; both were initially
      diagnosed as having lymphatic malformation. A biopsy specimen for one child and
      excision for the other showed that both lesions were congenital fibrosarcomas.
      Postoperative chemotherapy was administered to both children. One died within 6
      months of incisional biopsy from widespread metastatic disease; the other is
      still being treated. Congenital fibrosarcoma can be confused in its clinical
      presentation, radiographic findings, and histopathology with lymphatic
      malformation (cystic hygroma).

PMID- 7722836
TI  - Enterocolitis associated with Hirschsprung's disease: a clinical-radiological
      characterization based on 168 patients.
AB  - The enterocolitis associated with Hirschsprung's disease (HD) has not been
      clearly characterized. This study was undertaken to analyze the clinical and
      radiological findings of Hirschsprung's enterocolitis (HEC) in 168 patients
      treated from July 1974 through October 1992. HEC occurred in 57 patients (33.9%),
      either preoperatively (13; 7.7%) or postoperatively (36; 21.4%). In eight
      patients (4.8%), it occurred pre- and postoperatively. The number of bouts of HEC
      per patient ranged from one to six (mean, 2.2). The major presenting features
      were abdominal distension (83%), explosive diarrhea (69%), vomiting (51%), fever
      (34%), lethargy (27%), rectal bleeding (5%), and colonic perforation (2.5%).
      There were no deaths directly related to HEC. The analysis of 150 plain x-rays of
      the abdomen, taken at the onset of HEC or in between bouts, showed that colonic
      dilatation was the most sensitive radiological finding (90% sensitivity), but it
      had poor specificity (24%). However, an intestinal cutoff sign (gaseous
      intestinal distension with abrupt cutoff at the level of the pelvic brim) was
      both sensitive (74%) and specific (86%) for HEC. Barium enema was of limited
      value in the diagnosis of HEC bouts because most of the radiographic findings
      persisted for prolonged periods after cessation of such bouts. The authors
      conclude that (1) HEC can be characterized as abdominal distension and explosive
      diarrhea associated with the intestinal cutoff sign and (2) the occurrence of
      explosive diarrhea in any patient with HD is suggestive of HEC, even in the
      absence of systemic symptoms, and should be treated to avoid the morbidity and
      potential mortality of HEC.

PMID- 7722838
TI  - Recurring infantile digital fibromatosis: report of two cases.
AB  - There have been 100 reported cases resembling this rare entity. This type of
      fibroma differs from others in three respects: (1) clinically it is limited to
      the fingers and toes in infants, (2) it has a remarkable tendency to recur, and
      (3) morphologically it is characterized by the presence of cytoplasmic inclusion
      bodies. Herein the authors discuss two cases. This type of fibroma appears from
      birth to age 3 years in the digits; if correctly diagnosed and left alone, it
      will regress spontaneously. On the basis of the literature, the present cases
      were treated conservatively and had follow-up until the fibromas disappeared and
      did not recur.

PMID- 7722839
TI  - Repair of the high vagina in girls with severely masculinized anatomy from the
      adrenogenital syndrome.
AB  - In the most severe form of congenital adrenal hyperplasia in females, the vagina
      is located above the level of the external urethral sphincter. Sixteen of these
      patients had reconstruction with a pull-through technique described previously.
      Nine are now adults; six have coitus and three do not. Five are young and
      sexually immature. Two have been lost to follow-up.

PMID- 7722840
TI  - Transperitoneal closure of the internal ring in incarcerated infantile inguinal
      hernias.
AB  - Over a 6-year period, 14 infants with a total of 16 inguinal hernias (IH)
      underwent transperitoneal closure of the internal ring (TPIR). This was performed
      through a minilaparotomy, using a purse-string suture placed around the internal
      ring from within. A difficult inguinal dissection of an edematous and friable
      spermatic cord was avoided. TPIR was performed for incarceration in 13 of the
      infants and for recurrence of the hernia within 24 hours of herniotomy in one.
      There were no intraoperative problems, and during follow-up there was no evidence
      of testicular atrophy or recurrence of the hernia. This suggests that TPIR is a
      reliable and safe operation in babies for whom the alternative inguinal approach
      would be difficult. These situations include hernias that are irreducible and
      early recurrence in which dissection of the cord would risk damage to the vas
      deferens or testicular vessels.

PMID- 7722841
TI  - Modified Marcy repair of large indirect inguinal hernia in infants and children.
AB  - Based on a review of operative notes of recurrent inguinal hernia cases from the
      authors' primary series, a surgical technique modified from the Marcy repair is
      described. With this technique, emphasis is placed on preservation of the intact
      internal spermatic fascia and reduction in the size of the internal inguinal
      ring. Through the inguinal approach, the sleeve-like extension of the internal
      spermatic fascia is incised longitudinally along the cord and up to the internal
      ring. The cord structures are dissected off the sac, and as much of the fascial
      tissue as possible is preserved intact. Both edges of the fascial defect are
      approximated with an unabsorbable suture; great care is taken to not penetrate
      the wall of the sac. The same suture is then used for high ligation, via a stay
      suture placed on the transversalis fascia on the other side of the neck, to
      reduce the size of the internal ring. The technique can be used in premature
      babies who have a flimsy, easily torn sac, and in some cases of giant hernia with
      a widely dilated internal inguinal ring, if the direct wall integrity remains
      adequate.

PMID- 7722842
TI  - Human antibody responses to outer envelope antigens of Porphyromonas gingivalis
      serotypes.
AB  - Immunological studies examining the homogeneity of the major antigenic components
      of P. gingivalis have suggested 3 serotypes and have indicated a limited
      distribution of the serotypes in an individual patient. These studies prompted us
      to define the immunodominant antigens and distribution of immune responses to P.
      gingivalis serotypes. Serum IgG antibody levels in periodontitis patients in the
      present study were most frequently elevated above the normal subjects when tested
      against P. gingivalis serotype A (i.e., 33277). Nearly 1/3 of the patients showed
      significantly elevated antibody to multiple serotypes of the P. gingivalis
      apparently resulting from cross-reacting antigens. We determined distinctive
      differences among outer envelope protein and antigen patterns obtained from the
      three serotypes. Moreover, the results identified considerable similarities in
      the qualitative and quantitative antigen response patterns among patients to a
      particular serotype. There was a strong positive correlation between IgG antibody
      levels (ELISA) and the total level of reactivity determined in the immunoblots,
      as well as a positive correlation to the proportion of antibody to particular
      antigens. These findings suggest that responses to these antigens comprised a
      major portion of the response to the intact microorganism. Additionally, the
      detection of antibody to particular antigen bands was indicative of early
      responses to each of the P. gingivalis serotypes. The results of our study
      indicate that a subpopulation of periodontitis patients develop an extensive
      serum antibody response often to multiple serotypes of P. gingivalis and may
      define a patient population with a P. gingivalis disease. Finally, our results
      indicate a more consistent antigenic composition for P. gingivalis which may
      enhance the potential for strategies to immunologically interfere with disease
      caused by this microorganism.

PMID- 7722843
TI  - Model fit and measurement outcome in attachment measurements: a simulation study.
AB  - Serial attachment level measurements were simulated based on 2 hypothetical
      models of true change: 1) a burst model, where attachment changes rapidly over
      the duration of one measurement interval, but is unchanging before and after, and
      2) a linear model, where attachment changes at a constant rate over time.
      Normally distributed measurement error was added to the modeled attachment level
      change to produce the series of measurement simulations. It was then determined
      for each series whether a burst model or a linear model best fit the simulated
      measurement series for a range of overall attachment level changes. For series
      generated by a burst model, the burst model fit better than a linear model a
      significant proportion of the time at all attachment level changes. However, for
      series generated by a linear model, the burst model provided the best fit for
      attachment level changes that were less than 4 times the standard deviation of
      the measurement error. Estimates of change based on a linear model slightly
      overestimated change when the true underlying model was a burst model. Estimates
      of change based on a burst model slightly underestimated change when the true
      model was a burst model, but substantially underestimated change when the
      underlying model was a linear model. Model fit when assessed by the least squares
      criterion may not be a reliable guide to model validity.

PMID- 7722844
TI  - Evidence of a direct relationship between neutrophil collagenase activity and
      periodontal tissue destruction in vivo: role of active enzyme in human
      periodontitis.
AB  - To assess the temporal relationship between periodontal tissue destruction and
      the activity of collagenase, exudate from inflamed periodontal tissues was
      collected and latent and active collagenase activities were measured by a
      functional assay in a longitudinal cohort study. Comparisons were made between
      human subjects with either: 1) inflammation with a previous history of
      progressive loss of connective tissue and bone support (n = 14); 2) inflammation
      and previous history of bone loss but now clinically stable (n = 27); or 3)
      inflammation and no loss of bone support (n = 17). Experiments using specific
      enzyme inhibitors, blocking antibodies and SDS-PAGE fluorograph to identify the
      pattern of collagen substrate degradation demonstrated that the collagenase
      activity was derived from neutrophils and not from bacteria or other host cells.
      Active collagenase activity pooled from 6 sites per subject was respectively 5
      and 6-fold higher in the group with progressive loss of connective tissue
      compared to the groups with either inflamed tissues alone or with inflammation
      and previous bone loss. In contrast, latent collagenase was increased up to 2
      fold higher in the group with inflammation but no bone loss compared to the group
      with progressive lesions. Moreover, the ratio of active to total collagenase
      activity was 50% higher in the group with progressive lesions. Although in all
      subjects successive measurements of site-specific active collagenase 1 month
      apart demonstrated wide variation (r < 0.50), only in sites with progressive
      periodontal destruction was there significant increase of active collagenase with
      time (1.28 x 10(-4) collagenase units per day). There were also sharp elevations
      in active enzyme level at the time of detection of loss of connective tissue
      attachment in specific sites of 8 subjects. At the time of detection of
      connective tissue attachment loss, there was an overall 40% increase of pooled
      active collagenase activity in all subjects with progressive loss of connective
      tissue compared to pre-breakdown sampling times. These data provide strong in
      vivo evidence for a direct role of active neutrophil collagenase in the
      pathological destruction of periodontal connective tissue.

PMID- 7722845
TI  - Increased intracellular levels of lysosomal beta-glucuronidase in peripheral
      blood PMNs from humans with rapidly progressive periodontitis.
AB  - Release of potent lysosomal enzymes by degranulation of polymorphonuclear
      leukocytes (PMNs) in host gingiva may contribute significantly to tissue
      destruction and the pathogenesis of periodontal disease. A pilot study
      established that peripheral blood PMNs from humans with rapidly progressive
      periodontitis (RPP) contained significantly increased amounts of intracellular
      lysosomal beta-glucuronidase as compared to healthy controls. This investigation
      gained insight into the question: are the increased levels of beta-glucuronidase
      in persons with RPP an a priori genetically determined PMN characteristic, or a
      reactive phenomenon induced by the periodontal disease process during
      granulopoiesis? Twelve healthy controls and twelve otherwise healthy individuals
      with RPP participated in a repeated measures design to T0 (initial, baseline), T1
      (four weeks after disease control therapy), and T2 (two months later). At each
      visit clinical indices (GI, pocket depths, GCF flow, plaque index) were performed
      and peripheral blood obtained. PMNs were isolated and suspended as 5 x 10(6)
      cells in 2.0 ml of HBSS. PMN suspensions were tested for total intracellular beta
      glucuronidase, degranulation induced by 1 x 10(-6)M and 5 x 10(-7) M FMLP
      challenges, and unchallenged for non-specific enzyme release. PMNs from
      individuals with RPP contained significantly higher absolute amounts of beta
      glucuronidase and released greater absolute amounts at FMLP challenge at T0, T1,
      and T2 compared to controls. No relationship was found between any of the
      clinical indices and beta-glucuronidase levels and no pattern was discovered
      relating to the repeated measures over time. We conclude that RPP peripheral
      blood PMNs contain elevated levels of beta-glucuronidase that are not induced by
      the periodontal disease process.

PMID- 7722846
TI  - Identification and possible function of cathepsin G in gingival crevicular fluid
      from chronic adult periodontitis patients and from experimental gingivitis
      subjects.
AB  - The levels of cathepsin G in gingival crevicular fluid (GCF) from chronic adult
      periodontitis patients and experimental gingivitis subjects were determined both
      by activity measurement using N-benzoyl-(DL)-phenylalanine-2-naphthyl ester as a
      substrate and by enzyme immunoassay using anti-human cathepsin G IgG. The
      activity level of cathepsin G in GCF of both periodontitis and experimental
      gingivitis has no significant correlation with all measured clinical parameters.
      Western immunoblotting using antibodies specific for cathepsin G or alpha 1
      proteinase inhibitor revealed that the difficulty in demonstrating the
      association of its activity with the severity of these diseases was due largely
      to formation of the enzyme-inhibitor complexes. By contrast, statistically
      significant positive correlation was found between cathepsin G content in GCF of
      periodontitis, which was determined by enzyme immunoassay, and such clinical
      parameters as the GCF volume, the gingival index and probing depth. The increased
      cathepsin G content with increasing severity of periodontal inflammation was
      markedly diminished by the initial treatment. Although no significant activity
      was detectable in GCF of experimental gingivitis, a rapid increase of the
      immunoreactive cathepsin G was found in GCF at 3-5 d after refraining from oral
      hygiene measures, which rapidly decreased by 10 d. The progressively increased
      cathepsin G between 10th and 21st d rapidly decreased by cleaning of the teeth.
      The results indicate that cathepsin G is involved in the host's defensive
      mechanism against the invasion of etiologic microbes and/or the development of
      either periodontitis or gingivitis.

PMID- 7722847
TI  - Elastin derived peptides protect elastic fibres degradation by human neutrophil
      elastase: in vitro and in vivo studies using a mechanically induced rat gingival
      inflammatory model.
AB  - An elastin peptide (kE57) obtained from organoalkaline hydrolysis of calf
      ligamentum nuchae insoluble elastin, was isolated by gel permeation on Sephadex
      G150 and high performance liquid chromatography on a TSK G 3000 SW column. It
      possessed an average Mr = 57,000 and similar amino acids composition as its
      insoluble counterpart. kE57 behave as a competitive inhibitor of human neutrophil
      elastase (HNE) with Ki = 1.4 microM; it also inhibited porcine pancreatic
      elastase (PPE) but less efficiently Ki = 180 microM. Identification of elastic
      fibres in rat gingiva was ascertained by light and electron microscopic studies.
      Morphometric studies indicated that rat gingiva contained similar levels of
      elastic fibres (= 2%) as human skin; elastic fibres networks from both tissues
      also displayed high structural analogy. Gingival chronic inflammation was induced
      in rats by mechanical impaction associated with an hyperglucidic diet. After 5
      weeks, the levels of rat gingiva elastic fibres, decreased from Vv = 1.94 +/-
      0.1% to Vv = 1.02 +/- 0.06%. Local injections of kE57: 100 micrograms per day, 5
      days a week for 5 weeks did restore the integrity of the gingiva elastic fibres
      network: Vv = 1.84 +/- 0.1. Without influencing leucocyte infiltration, it is
      proposed that elastin-derived peptides, acting as potent competitive inhibitor of
      neutrophil elastase involved in periodontitis, might be of therapeutic value.

PMID- 7722848
TI  - Predominant microflora of severe, moderate and minimal periodontal lesions in
      young adults with rapidly progressive periodontitis.
AB  - The purpose of this investigation was to study the microflora of severe, moderate
      and minimal periodontal lesions, in young adults with rapidly progressive
      periodontitis (RPP). Subgingival plaque samples were taken from 142 periodontal
      lesions in 10 young adults aging 25 to 35 years. The examination of the
      subgingival microflora indicated that certain species, including Porphyromonas
      gingivalis, Bacteroides forsythus, Fusobacterium nucleatum, Actinobacillus
      actinomycetemcomitans, and Campylobacter species were found to be predominant in
      severe periodontal lesions. B. forsythus, P. gingivalis, Prevotella intermedia,
      F. nucleatum, Capnocytophaga ochracea, were predominant in medium lesions while
      Streptococcus species and Actinomyces species, C. ochracea, Haemophilus segnis
      and Veillonella parvula, were found in higher levels in minimal periodontal
      lesions.

PMID- 7722849
TI  - Calibration and reliability of the Periotron 6000 for individual gingival
      crevicular fluid samples.
AB  - The Periotron 6000 fluid analyser has become widely used as a diagnostic tool for
      a variety of oral diseases and recent work has questioned its reliability. This
      paper investigates for the first time, the detailed calibration curves of 2
      Periotron 6000 machines across a range of 23 different fluid volumes. Within and
      between machine reliability is analyzed and the shape of the calibration line
      determined. The measurement errors incurred by using a single fluid sample, as
      opposed to mean values of triplicate samples are also determined. We conclude
      that there are 3 sections to the calibration line, 2 linear and a quadrilateral
      zone, and that 2 separate regression equations should be used; from 0-0.1
      microliter and from 0.1-1.0 microliter. Within machine calibration errors were
      only 3.2 +/- 7.5%, but values for volumes below 0.2 microliter were as high as
      18.7%. Using a single fluid sample rather than mean values of multiple samples,
      incurred a further 4 +/- 4% error, which was as high as 7% for volumes lower than
      0.12 microliter. Whilst significant differences in volume reading existed between
      different machines (p < 0.0004) and between the same volumes of different fluids
      (p < 0.00001), individual Periotron calibrations were extremely reproducible and
      reliable. We conclude that the Periotron 6000 is a reliable and convenient
      instrument for measuring fluid volumes greater than 0.2 microliter. For volumes
      lower than 0.2 microliter errors in measurement may be too high for some
      investigations, but this is likely to be due to problems with evaporation and
      with measurement technique, rather than errors directly due to the Periotron
      itself. Finally, for optimum accuracy, the digital display should be re-set to
      zero after each sample is measured.

PMID- 7722850
TI  - Shyness and public self-consciousness: additive or interactive relation with
      social interaction?
AB  - Shy people are characterized as engaging in self-derogatory thinking leading to
      anxiousness and inhibition, while people who are publicly self-conscious are
      focused on the impression they create on others. In addition, public self
      consciousness has been described as an antecedent of shyness. In the present
      research, we tested additive versus interactive hypotheses about the association
      of shyness and public self-consciousness with dysfunctional social interaction.
      Undergraduate men varying in shyness and public self-consciousness engaged in a
      conversation with an unfamiliar woman confederate. Following the conversation,
      subjects completed self-report measures focusing on their responses during the
      conversation. Only main effects for shyness and public self-consciousness were
      found, supporting an additive hypothesis. Shyness was related to all dependent
      variables reflecting a negative self-bias, while public self-consciousness was
      not. In particular, shyness was inversely related to the balance of subjects'
      positive and negative thoughts and to reported use of protective as well as
      avoidance of acquisitive self-presentation responses. Public self-consciousness
      was positively related to use of protective self-presentation responses but
      unrelated to acquisitive responses.

PMID- 7722851
TI  - Do obese women have poorer social relationships than nonobese women? Reports by
      self, friends, and coworkers.
AB  - Both theory and research suggest that obese women may have relatively poor social
      relationships even if their self-reports about their relationships do not differ
      from the reports of nonobese women. Seventy-seven obese and 78 nonobese women
      completed self-report measures of social anxiety, social self-esteem, social
      competence, social network size, and perceived social support from friends and
      family. Friends and coworkers also rated these women on the same measures. The
      self-reports of obese and nonobese women did not differ significantly on any of
      these social measures, and ratings from friends and coworkers of obese women were
      not different from ratings of nonobese women by friends and coworkers. These
      results suggest that obese women may be able to overcome prejudice against obese
      people in their relationships with others.

PMID- 7722852
TI  - Development and validation of a new body-image assessment scale.
AB  - This investigation reports the development and validation of a new and improved
      body-image assessment tool, the Contour Drawing Rating Scale, consisting of nine
      male and nine female contour drawings. The drawings were designed with detailed
      features, are of precisely graduated sizes, and are easily split at the waist for
      accurate upper and lower body comparisons. Initial evidence of the scale's
      reliability and validity supports its use as a measure of body-size perception.

PMID- 7722853
TI  - Chronic self-destructiveness and self-defeating personality: similarities and
      differences.
AB  - This study attempts to determine whether the Chronic Self-Destructiveness Scale
      (CSDS; Kelley, Byrne, et al., 1985) would be better described as a measure of
      impulsiveness or self-defeating behavior in the Diagnostic and Statistical Manual
      of Mental Disorders (3rd ed., Rev. [DSM-III-R]; American Psychiatric Association,
      1987) diagnostic sense. Subjects completed the CSDS, the Self-Defeating Scale
      (Schill, 1990), and measures of restraint, distress, and psychopathy. Based on
      the correlations among these scales, we suggest that the CSDS is better described
      as a measure of impulsiveness, poor judgment, and immediate gratification, rather
      than a measure of Self-Defeating Personality, which keeps the individual in a
      victim position.

PMID- 7722854
TI  - Personality, life events, and depression.
AB  - The Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan,
      1976a) and the Sociotropy-Autonomy Scale (SAS; Beck, Epstein, Harrison, & Emery,
      1983) have been used virtually interchangeably to assess personality styles that
      are believed to influence the development of depressive symptomatology in the
      context of specific negative life events. This study examined the extent to which
      these two personality measures overlap and tested the congruency hypothesis. The
      congruency hypothesis predicts that levels of depression vary as a function of
      the interaction between personality and the occurrence of thematically related
      negative life events. Results indicated that the DEQ Dependency and the SAS
      Sociotropy scales appear to measure similar constructs, whereas the DEQ Self
      Criticism and SAS Autonomy scales do not appear to measure similar constructs.
      Further, support was obtained for the congruency hypothesis using either the DEQ
      Dependency scale or the SAS Sociotropy scale; however, support for this
      hypothesis was not obtained for the DEQ Self-Criticism scale or the SAS Autonomy
      scale.

PMID- 7722855
TI  - Impact of simulating borderline personality disorder on the MMPI-2: a costs
      benefits model employing base rates.
AB  - This investigation extends current work on the impact of role-specific response
      sets on dissimulated Minnesota Multiphasic Personality Inventory-2 (MMPI-2;
      Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) profiles. Specifically,
      one group of subjects was given specific symptom information and instructed to
      simulate borderline personality disorder on the MMPI-2. This dissimulation
      performance was compared to a clinical comparison group of clients diagnosed with
      borderline personality disorder, a group of subjects instructed to simulate major
      depression, and a group of subjects who responded honestly to the MMPI-2. In both
      simulating conditions, subjects produced significantly higher elevations on a
      majority of clinical and validity scales than the clinical comparison group. A
      rigorous evaluation of the F scale was conducted to provide a range of predictive
      values for different F scale cutting scores for detecting malingering.
      Sensitivity, specificity, and positive and negative predictive power were
      computed for this range of F scale values. A similar analysis was conducted for
      the Borderline Personality Disorder Scale (BPDsc) of Morey, Waugh, and Blashfield
      (1985). These results are integrated with extant research. A costs-benefits model
      is proposed for employing F scale cutting scores in clinical situations with
      different base rates of malingering.

PMID- 7722856
TI  - Interrelationship between MMPI-2 and Rorschach variables in a sample of Vietnam
      veterans with PTSD.
AB  - We examined interrelationships between theoretically related MMPI-2 and Rorschach
      variables in a sample of Veterans Affairs outpatients with Posttraumatic Stress
      Disorder (PTSD). Subjects were 20 White Vietnam combat veterans diagnosed with
      PTSD who completed the Rorschach and MMPI-2 as part of a comprehensive
      evaluation. Correlations were calculated for variables in three groups: validity,
      depression and anxiety, and thought disturbance. Results showed strong
      relationships between m, MOR, and the Dramatic special score of the Rorschach and
      MMPI-2 indices of distress. Positive relationships were also found for some
      indicators of thought disturbance, whereas correlations for other depressive
      indicators were not significant. Findings are discussed with regard to
      implications for the clinical assessment of combat-related PTSD and future
      directions for assessment research.

PMID- 7722857
TI  - Subscales within the dependency factor of the Depressive Experiences
      Questionnaire.
AB  - Recent theoretical formulations differentiate two types of depressive
      experiences: one focused on interpersonal issues, such as loss, abandonment, and
      loneliness; the other focused on issues of self-esteem, such as failure, guilt,
      and lack of self-worth and autonomy. The Depressive Experiences Questionnaire
      (DEQ; Blatt, D'Afflitti, & Quinlan, 1976, 1979) assesses these two types of
      depression. Symptom-based measures of depression (i.e., the Beck Depression
      Inventory, Beck, Rush, Shaw, & Emery, 1979) have highly significant correlations
      with the DEQ Self-Criticism factor but only marginally significant correlations
      with the DEQ Dependency (or interpersonal) factor. Through the use of facet
      theory and Smallest Space Analysis (Guttman, 1982a), two facets were identified
      within the DEQ Dependency factor that appear to assess two different levels of
      interpersonal relatedness. One facet, labelled dependence, includes items
      expressing feelings of helplessness; fears and apprehensions about separation and
      rejection; and intense, broad-ranging concerns about possible loss unrelated to a
      particular relationship. The second facet, labelled relatedness, includes items
      that consider feelings of loss and loneliness in reaction to disruption of a
      relationship with a particular person. The dependence facet had significantly
      higher correlations with measures of depression, whereas the relatedness facet
      had significantly higher correlations with measures of psychological well-being,
      especially in women. Thus, the DEQ Dependency factor appears to contain two
      facets that assess interpersonal relatedness at different developmental levels
      and correlate differentially with measures of depression and of psychological
      well-being.

PMID- 7722858
TI  - Initial validation of the Personality Assessment Inventory-Spanish version with
      clients from Mexican American communities.
AB  - Psychological assessment of Hispanic populations are thwarted by the absence of
      clinical research on comparability of Spanish translations and the stability of
      their findings. In this study we examined the potential usefulness of the Spanish
      Personality Assessment Inventory (PAI; Morey, 1991) for Hispanic clients residing
      in Mexican American communities. We administered the Spanish version on two
      occasions to 48 monolingual clients and the Spanish and English versions to 21
      bilingual clients. Results indicated that the clinical scales had a moderate to
      good correspondence for Spanish-English (M r = .72) and good test-retest
      reliability for Spanish-Spanish (M r = .79). Much more variation was observed for
      the validity scales and the treatment/interpersonal scales. Also more variability
      was observed in the convergence of elevations across administrations. Because of
      these mixed results, we discuss the potential usefulness of the PAI clinical
      scales to screen for major psychopathology.

PMID- 7722859
TI  - The North Carolina Dissociation Index: a measure of dissociation using items from
      the MMPI-2.
AB  - The development of a new measure of dissociation using items from the Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham,
      Tellegen, & Kaemmer, 1989) is described. In Experiment 1, 525 college students
      were administered a measure of hypnotic susceptibility and completed several
      specialized measures of dissociation or dissociation-like experiences. The new
      measure, the North Carolina Dissociation Index (NCDI) demonstrated adequate
      internal consistency and good convergent validity. In Experiment 2, the NCDI
      demonstrated adequate internal consistency and test-retest reliability with a
      different sample of college students. Moreover, NCDI scores showed a relatively
      strong correlation with an interview-based measure of dissociative symptoms. In
      addition, a small sample of students with dissociative disorders had
      significantly higher NCDI scores than students with anxiety disorders and normal
      control subjects. In Experiment 3, 19 gang combat veterans were administered a
      semistructured diagnostic interview and the MMPI-2. Subjects who were diagnosed
      with Posttraumatic Stress Disorder (PTSD) scored significantly higher on the NCDI
      than subjects who did not have PTSD. The NCDI is intended primarily as a tool in
      settings where the MMPI-2 is routinely administered.

PMID- 7722860
TI  - Development of a short form of the adolescent version of the Defense Mechanisms
      Inventory.
AB  - This article describes the construction of a short form of the adolescent version
      of the Defense Mechanisms Inventory (DMI; Gleser & Ihilevich, 1969; Ihilevich &
      Gleser, 1986). The DMI is a paper-and-pencil test for which subjects are asked to
      describe their reactions to 10 hypothetical dilemmas. The responses involve a
      forced choice method in which each of the alternative responses represent one of
      five defense clusters entitled Turning Against the Object, Principalization,
      Turning Against the Self, Reversal, and Projection. Two hundred ninety-five
      adolescent psychiatric patients (122 boys and 173 girls) ages 12-16 were
      administered the adolescent form of the DMI. Based on an analysis of each of the
      10 dilemma stories, a 6-story short form was devised. Correlations between this
      short form and the long form of the DMI ranged from .90 to .95 on the five
      defense scales, with no significant effect of gender. Internal reliability
      estimates of the short form scales were also favorable. These results indicate
      that the short form of the adolescent DMI is an acceptable substitute for the
      lengthier inventory from which it was derived and is more utilizable in clinical
      and research settings.

PMID- 7722861
TI  - Comparison of MMPI-2 and MMPI clinical scales and high-point scores among
      methadone maintenance clients.
AB  - Methadone client volunteers completed the Minnesota Multiphasic Personality
      Inventory (MMPI; Hathaway & McKinley, 1967) and MMPI-2 (Butcher, Dahlstrom,
      Graham, Tellegen, & Kaemmer, 1989) on consecutive days. MMPI-2 T-scores were
      lower by a mean of 4.7 on the clinical scales; when 5 points were added to MMPI-2
      T-scores the mean difference was 2.3. Rank order of subjects on scale T-scores
      was not significantly different between the two instruments. High-point
      similarity for clinically elevated profile pairs ranged from 61% to 92%,
      depending upon definition of similarity.

PMID- 7722862
TI  - Hopkins Symptom Checklist-25, Hmong version: a screening instrument for
      psychological distress.
AB  - The Hopkins Symptom Checklist (HSCL-25; Mattsson, Williams, Rickels, Lipman, &
      Uhlenhuth, 1969) was translated into the Hmong language and administered to 159
      Hmong adults, 73 nonclinical and 86 mental health clients. The instrument
      demonstrated internal consistency of .97 and had a split-half coefficient of .92
      and test-retest reliability of .90. Mental health clients produced scores that
      were significantly higher than those of nonclinical participants on the Anxiety,
      Depression, and Total scores. Consistent with expectations, Hmong more intensely
      affected by the casualties of war, those currently unemployed, those older, and
      those with less education tended to report more symptoms of anxiety and
      depression. The Hmong version of the HSCL-25 provided a sensitivity of 100%,
      specificity of 78%, and overall accuracy of 89%, demonstrating that it is a
      useful screening tool for assessing general distress and anxiety problems in
      Hmong people.

PMID- 7722863
TI  - Comparison of MCMI-II and 16PF validity scales.
AB  - We administered the Millon Clinical Multiaxial Inventory-II (MCMI-II; Millon,
      1987) and the Sixteen Personality Factors Inventory (16PF; Cattell, Eber, &
      Tatsuoka, 1970) to 131 outpatients in marital therapy and tested the correlation
      between the validity scales of the two instruments. The results indicated that
      MCMI-II Disclosure and Debasement scales were positively correlated with the 16PF
      Fake-Bad scale and negatively correlated with the 16PF Fake-Good scale. The MCMI
      II Desirability scale was significantly correlated with the 16PF Fake-Good scale.

PMID- 7722864
TI  - Correspondence of the MMPI-2 and MCMI-II in male substance abusers.
AB  - The Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom,
      Graham, Tellegen, & Kaemmer, 1989) and the Millon Clinical Multiaxial Inventory
      II (MCMI-II; Millon, 1987) were given to 306 men with substance use disorders,
      and scores on 45 MMPI-2 scales and 25 MCMI-II scales were analyzed separately
      into seven and five principal components. The first two components from both
      tests accounted for a majority of the explained variance and were well correlated
      across tests. They were labeled Emotional Maladjustment and Antisocial Traits for
      both tests.

PMID- 7722865
TI  - Are the annual reproductive and body weight rhythms in the male European hamster
      (Cricetus cricetus) dependent upon a photoperiodically entrained circannual
      clock?
AB  - Most of the data obtained so far on the European hamster (Cricetus cricetus)
      suggest direct photoperiodically driven seasonal changes in sexual activity and
      body weight. The results of the present long-term study support the hypothesis
      that these annual changes are the expression of photoperiodically driven
      endogenous circannual rhythms. When subjected following capture (April-May) to
      constant conditions of long photoperiod (LP) and constant temperature a large
      number of the European hamsters present, in September-December, complete gonadal
      atrophy associated with a decrease in body weight. A sexual reactivation as well
      as an increase in body weight are observed in the same animals between January
      and April. Of the six animals that survived long enough, two only presented
      partial gonadal atrophy during the second year. These observations clearly
      demonstrate that the decline in sexual activity in subjective autumn does not
      require a decrease in photoperiod, at least in the first year. Theoretically, the
      observed rhythms, if circannual in nature, would be generated by a self-sustained
      annual oscillator (circannual clock) able to function in the absence of a
      photoperiodic input. Pinealectomy makes animals unable to detect or measure
      photoperiodic information. Of the six European hamsters tested (pinealectomized
      in June and then kept continuously under LP), five showed clear annual rhythms in
      body weight and reproductive capacities for two consecutive years. Clearly
      endogenous annual rhythms were expressed in these conditions. To be entrained to
      a 1-year period, such a circannual clock should, however, be able to react to
      either LP and/or to short-photoperiod (SP), at least at certain periods of the
      annual cycle. In animals exposed to LP in August or October, after gonadal
      atrophy had been established by exposure to natural SP, gonadal regrowth started
      in December or January, about 2 to 3 months earlier than in animals kept outside
      or in experimental SP. With the same experimental conditions, exactly the same
      results were obtained in pinealectomized animals; thus stimulatory effect of LP
      or LP-induced phase advance of the circannual clock can be excluded. The absence
      of the SP information would then induce such reaction. In animals kept under
      constant LP and temperature following capture, however, pinealectomy in January-
      when all animals are sexually active--induces gonadal atrophy within--weeks. This
      clearly demonstrates that LP is stimulatory at this time of the subjective year.

PMID- 7722866
TI  - Inhibitory effect of melatonin on production of IFN gamma or TNF alpha in
      peripheral blood mononuclear cells of some blood donors.
AB  - Melatonin, the main pineal hormone, has been shown to influence many biological
      functions, including the immune response and cancer growth. The purpose of this
      study was to examine the effect of melatonin on the production of interferon
      gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) by peripheral blood
      mononuclear cells (PBMC) in culture. Melatonin at physiological concentrations
      fails to induce production of IFN or TNF by PBMC in culture but causes a dose
      related inhibition of production of both cytokines if the PBMC are stimulated
      with phytohaemagglutinin. This inhibitory effect occurs in only 22% of cases
      (melatonin-sensitive) but disappears when the cells are stored at 4 degrees C for
      4 days. The effect of melatonin appears not to be mediated by opiates nor to be
      correlated with the age, sex, or blood group of donors, but seems to be
      influenced by the seasonal time of blood collection. These results provide
      further evidence for an interaction between melatonin and the immune system and
      suggest that the effect of melatonin on production of IFN and TNF may be mediated
      by various factors not yet fully understood.

PMID- 7722867
TI  - Response of collared lemmings to melatonin: I. Implants and photoperiod.
AB  - We examined the effect of constant-release melatonin capsules on the physiology
      and morphology of female collared lemmings exposed to either chronic long
      (22L:2D) or short (8L:16D) photoperiod, or to a change in photoperiod. When
      animals were maintained on unchanging long or short photoperiod, subcutaneous
      melatonin implants were without effect. However, when animals were reared on
      either 22L:2D or 8L:16D and transferred to the alternate photoperiod at weaning,
      melatonin (implanted at weaning) prevented most photoperiod-related responses. At
      sacrifice (after 8 weeks of treatment), melatonin-implanted animals exposed to a
      change in photoperiod did not differ from animals remaining in the original
      photoperiod with respect to pelage color, bifid claw size, uterine mass, or serum
      prolactin (PRL). In contrast, regardless of treatment, animals exposed to a
      photoperiod transfer developed a body mass that partially or fully reflected that
      characteristic of the secondary photoperiod; i.e., both control- and melatonin
      implanted animals transferred from long to short photoperiod developed a large
      body mass. These results indicate that masking the endogenous melatonin rhythm
      via constant-release melatonin implants renders collared lemmings unable to
      respond to a change in photoperiod with respect to most physiological parameters.
      However, the striking seasonal change in body mass experienced by collared
      lemmings appears to be at least partially independent of a melatonin signal.

PMID- 7722868
TI  - Response of collared lemmings to melatonin: II. Infusions and photoperiod.
AB  - Collared lemmings (Dicrostonyx groenlandicus) show much phenotypic plasticity
      when exposed to photoperiods of varying length. In addition to "long day" and
      "short day" morphologies, apparent when animals are exposed to 22L:2D and 8L:16D,
      respectively, animals with intermediate features appear when collared lemmings
      are placed on day lengths ranging from 18L:6D to 14L:10D. Body mass, body
      composition, pelage color and length, the presence and size of a bifid claw, and
      reproductive condition are all influenced by ambient day length. We tested the
      hypothesis that variations in the melatonin signal mediate the physiological and
      morphological responses observed in collared lemmings housed in various
      photoperiods. One group of collared lemmings was fitted with a subcutaneous
      cannula at weaning and infused for 8 weeks with 2, 6, or 14 hr melatonin or 14 hr
      vehicle daily while housed in constant light (LL). Additional groups were
      transferred to LL, 20L:4D, 16L:8D, or 8L:16D (all uninfused). The response of the
      animals to both melatonin infusion and photoperiod was graded; the degree to
      which the "winter" morphology developed was proportional to the length of both
      the melatonin infusion and the scotophase. Both the 14 hr infusion and the 8L:16D
      photoperiod promoted development of the characteristic "winter" traits: large
      body size, white pelage, bifid claw, small uterus, and low serum prolactin (PRL).
      Conversely, treatment with the 2 hr infusion or exposure to the long photoperiods
      (LL, 20L:4D) resulted in a "summer-like" morphology. Infusion of 6 hr melatonin
      per day or exposure to 16L:8D produced animals with an intermediate physiology.
      Overall, the results support the hypothesis that variations of the endogenous
      melatonin rhythm mediate the effect of photoperiod length on seasonal
      physiological and morphological changes in collared lemmings.

PMID- 7722869
TI  - Identification and characterization of 2[125I]-iodomelatonin binding sites in the
      rat epididymis.
AB  - Putative melatonin receptors in different parts of the male reproductive system
      of rats (Sprague-Dawley), mice (ICR), hamsters (Syrian) and guinea pigs (Dunkin
      Hartley), rat epididymal sperm, and boar and human semen were studied by a
      radioreceptor assay using 2[125I]iodomelatonin as the radioligand. There was
      limited or no detectable binding of 2[125I]iodomelatonin to membrane preparations
      of rat testis, seminal vesicles, prostate, or sperm from rat, human, and boar.
      However, significant bindings of 2[125I]iodomelatonin to the epididymides of rat,
      mouse, hamster, and guinea-pig were demonstrated. The relative binding capacities
      of 2[125I]iodomelatonin to the distal epididymal segment in different rodent
      species was of the order rat mouse hamster guinea pig. The relative number of
      binding sites was much lower in the proximal segment than in the distal segment
      of epididymis. 2[125I]iodomelatonin binding to the distal segment of rat
      epididymis was studied in detail. The binding sites fulfilled all criteria for a
      receptor site; being stable, saturable, reversible, and of high affinity. The
      binding had an equilibrium dissociation constant (Kd) of 62.6 +/- 7.79 pmol/l (n
      = 7) and a density (Bmax) of 1.55 +/- 0.16 fmol/mg protein (n = 7). The Hill
      coefficient approached 1.0, suggesting a single class of 2[125I]iodomelatonin
      binding sites. Pharmacological studies revealed that these 2[125I]iodomelatonin
      binding sites were specific for melatonin receptors. In addition, there was an
      age-related change in the 2[125I]iodomelatonin binding sites in the rat distal
      epididymal segment. The binding increased from a lower value in 1-month-old rats
      to a higher adult value in the 1 1/2- to 24-month-old animals.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7722870
TI  - [Relationship between myocardial perfusion state immediately after reperfusion
      therapy and left ventricular wall motion improvement in patients with acute
      myocardial infarction].
AB  - The relationship between myocardial contrast echocardiography and improvement of
      the left ventricular wall motion was studied as an indicator of the prognosis of
      patients with acute myocardial infarction. Ten patients with acute anterior
      myocardial infarction who demonstrated successful reperfusion (improved to TIMI
      grade III) and patency of the responsible coronary artery during the chronic
      stage (one month after the onset) were selected. The contrast study used 2 ml of
      sonicated iopamidol injected into the left coronary artery. Two-dimensional
      echocardiograms were taken at the level of papillary muscle on the short axis for
      recording in VTR. The results of the contrast study were evaluated using a
      contrast defect score based on the degree and width of the contrast defect.
      Percent wall motion improvement was measured as an index of improvement of the
      left ventricular wall motion and CKmax was used for estimating the extent of
      myocardial necrosis. There was a good correlation between contrast defect score
      and CKmax (r = 0.853) or % wall motion improvement (r = 0.77). No correlation was
      found between coronary occlusion time and CKmax nor between coronary occlusion
      time and % wall motion improvement. The results suggest that if the score is
      high, recovery of left ventricular wall motion cannot be expected in patients
      with acute myocardial infarction who demonstrate successful reperfusion. In such
      cases, myocardial perfusion has not been effectively restored and myocardial
      necrosis extended over a wide area. If the score is low, recovery of the wall
      motion can be expected in the chronic stage even though abnormal left ventricular
      wall motion area is extensive immediately after reperfusion therapy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7722872
TI  - [M-mode echocardiographic evaluation of contractility and distensibility of
      infarcted area in patients with inferior myocardial infarction].
AB  - The relationship between degree of myocardial damage and distensibility and
      contractility of the infarcted area was evaluated by M-mode echocardiography.
      Echocardiography was performed to evaluate the left ventricular inferior wall
      motion in 33 patients with myocardial infarction (MI) at mean 87.03 days after
      onset. Exercise 201Tl single photon emission computed tomography (SPECT) was also
      performed. Eighteen non-MI subjects were analyzed as a control group. Percentage
      Tl uptake (% TU) of the infarcted area, calculated from SPECT scans, was
      positively correlated with the mean systolic inferior wall velocity (mSIWV), and
      with the mean diastolic inferior wall velocity (mDIWV) (r = 0.36, p < 0.05; r =
      0.47, p < 0.01, respectively). These data indicate that both velocities were
      decreased in proportion to the degree of myocardial damage. The patients with MI
      were divided into two groups based on % TU determined by SPECT. Group I consisted
      of 17 patients with % TU > or = 60%, and group II 16 patients with % TU < 60%.
      The patients in group I were diagnosed as having slight myocardial damage, and no
      relationship between % TU and mSIWV or mDIWV was observed. All patients in group
      II were diagnosed as having severe myocardial damage, and % TU was closely
      correlated with mSIWV (r = 0.72, p < 0.01) and with mDIWV (r = 0.70, p < 0.01).
      All patients in both MI groups displayed a slower mDIWV than the the control
      subjects (p < 0.05 for group I and p < 0.01 for group II).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7722871
TI  - [Serum lipid states in elderly patients with acute myocardial infarction:
      comparison between patients aged 60 to 79 and 80 years and over].
AB  - Recently, the prevalence of acute myocardial infarction (AMI) in the elderly
      patients has increased. The clinical features have not been extensively studied,
      so this study attempted to clarify the clinical course and prognosis of elderly
      patients with AMI. The patients were divided into two groups, those over 80 years
      old and those between 60 and 79 years old. The clinical symptoms,
      electrocardiographic findings, complications, and short-term prognosis were
      compared. The serum lipid levels were compared between the AMI groups and age
      matched control groups consisting of subjects without sclerotic heart disease.
      There was no significant difference in clinical symptoms between the two groups,
      electrocardiographic findings, incidence of complications, and mortality. The
      total cholesterol and LDL cholesterol levels, and atherogenic index were
      significantly higher in the 60-79 years old AMI group, but no significant
      difference was observed in the 80 years and over AMI group compared to the
      control group. The HDL cholesterol level of the 60-79 years old AMI group was
      significantly lower, but no significant difference was observed in the 80 years
      and over group. There was no significant difference in triglyceride level in
      either AMI group. Therefore, in patients aged 60-79 years hyperlipidemia is a
      risk factor for ischemic heart disease, but the relationship between serum lipid
      and AMI is not positively established in patients older than 80 years. These
      results suggest that the significance of hyperlipidemia in patients over 80 years
      old should be reconsidered.

PMID- 7722873
TI  - [Ultrasonic tissue characterization of diseased myocardium by scanning acoustic
      microscopy].
AB  - Ultrasonic tissue characterization of the myocardium has become very important
      because the requirement for evaluating local cardiac function has increased. In
      the present study, the acoustic properties of the tissue elements in myocardial
      infarction were measured by a specially developed scanning acoustic microscope
      (SAM) system, and the echo intensity of the infarcted myocardium was assessed.
      Ten samples of infarcted myocardium obtained at autopsy were formalin-fixed,
      paraffin-embedded and cut into 10 microns thick slices. The SAM system was
      operated in the frequency range of 100 to 200 MHz. The values of the attenuation
      constant and sound speed were measured in five tissue elements, normal
      myocardium, degenerated myocardium, fibrosis, granulation, and hemorrhage by
      comparing the optical microscopic image and acoustic images. The density of each
      tissue element was measured by the CuSO4 method, and the specific acoustic
      impedance was calculated by multiplying the sound speed and the density of each
      tissue element. The specific acoustic impedance was 1.75 x 10(6) Ns/m3 in normal
      myocardium, 1.69 x 10(6) Ns/m3 in degenerated myocardium, and 1.85 x 10(6) Ns/m3
      in fibrosis. The intensity of the reflected ultrasound at the interface between
      two different tissue elements was calculated by the difference of specific
      acoustic impedance. Using the sensitivity changing method in clinical
      echocardiography, the intensity of myocardial scar was -15 dB compared to the
      pericardial echo. The corrected ideal ultrasonic reflection between degenerated
      myocardium and fibrosis was calculated as -15.4 dB. The results suggest that
      measurement of acoustic properties is very important to provide basic data for
      ultrasonic characterization of myocardium tissue.

PMID- 7722874
TI  - [Progression of senile aortic valve calcification: echocardiographic and clinical
      assessment].
AB  - Factors involved in the progression of senile aortic valve calcification were
      evaluated by analyzing the clinical and echocardiographic characteristics of
      patients older than 69 years with senile aortic valve calcification. The patients
      were divided into three groups; group 1: 46 male and 40 female patients with
      calcification of one cusp and almost normal pliability of three cusps, group 2:
      48 males and 55 female patients with calcification of two or three cusps, mildly
      reduced pliability of calcified cusps, and aortic valve area (AVA) > or = 2.0
      cm2, group 3: 26 male and 31 female patients with calcification of two or three
      cusps, significantly reduced pliability of calcified cusps, and AVA < or = 1.5
      cm2. There were no significant differences in age, weight, height, left
      ventricular dimension, or left ventricular wall thickness between these three
      groups. For male patients, the end-diastolic maximum left ventricular outflow
      tract dimensions (LVOT) in groups 1, 2, and 3 were 20 +/- 2 mm, 19 +/- 2 mm (p <
      0.01 vs group 1), and 17 +/- 3 mm (p < 0.001 vs group 1, p < 0.01 vs group 2),
      respectively. For female patients, the LVOTs of groups 1, 2, and 3 were 18 +/- 2
      mm, 16 +/- 2 mm (p < 0.001 vs group 1), and 16 +/- 2 mm (p < 0.001 vs group 1),
      respectively. Reduction in LVOT was not associated with left ventricular
      hypertrophy or decrease in dimension of aortic annulus. In female patients, the
      frequency of mitral annular calcification of group 3 was 61% [p < 0.05 vs group 1
      (35%), p < 0.01 vs group 2 (25%)].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722875
TI  - [Clinical significance of transesophageal echocardiography for evaluation of
      patients after Bentall's operation: detection of graft failure].
AB  - Leakage from the composite graft at the site of coronary anastomosis into the
      perigraftal space (pseudoaneurysm) is an important complication of Bentall's
      operation. The clinical value of transesophageal echocardiography (TEE) for
      detecting this graft failure was evaluated in 30 patients who underwent Bentall's
      operation or Piehler's modification. Three patients (10%) had perigraftal leakage
      (pseudoaneurysm). TEE demonstrated the leakage site which was not clearly showed
      by computed tomography (CT) scan and aortography. The detection rate of the
      anastomosed native coronary artery was 89% (left: 100%, right: 67%).
      Interposition graft by Pichler's modification method was detected in 96% (left:
      100%, right: 92%) of cases by TEE, but only in 43% (left: 57%, right: 29%) by CT
      scan (left: p < 0.005, right: p < 0.0001). The detection rate of the right
      coronary artery, interposition graft to right coronary artery, and their color
      signals were lower than those of the left coronary artery. TEE has considerable
      diagnostic value in evaluating patients after Bentall's operation.

PMID- 7722876
TI  - [Introduction to index of the failing heart syndrome].
AB  - On the occasion of the 42nd Scientific Meeting of the Japanese College of
      Cardiology, a presentation of the methods of the recognition or some indices of
      heart failure was given to encourage comprehensive discussion of failing heart
      syndrome. During the last 10 years, several multicenter, randomized, placebo
      controlled studies of the efficacy and safety of drugs in patients with heart
      failure have been performed in western countries, resulting in the evolution of a
      new concept of heart failure based on pathophysiologic and therapeutic
      approaches. However, many trials of new drugs for heart failure shown to be
      efficacious in western countries have failed to be effective in Japan. The
      reasons for this discrepancy might be based on differences of the causes of
      chronic heart failure, but also on differences in understanding. All Japanese
      cardiologists know that the prevalence of left ventricular failure evolving
      rapidly after acute myocardial infarction in Japan is far less common than in
      western countries. Recent evolution of pathophysiologic concepts of heart failure
      is derived from the experimental and clinical observations of myocardial failure.
      The effects of mechanical overload on failing heart might be an unfashionable
      topic now, but in Japan, all factors affecting failing heart should be carefully
      considered when heart failure is treated, because the controlling factor inducing
      heart failure is hard to identify.

PMID- 7722877
TI  - [Interpretation of the apex beat].

PMID- 7722878
TI  - [Effects of 2-(3,4-dimethoxyphenyl)ethylamine derivative (ecabapide, DQ-2511) and
      its metabolites on water-immersion restraint stress-induced gastric ulcers in
      rats].
AB  - Ecabapide (DQ-2511) has been demonstrated to be effective in preventing water
      immersion restraint stress ulceration of rats. In the present study, we aimed to
      define the active molecular features of ecabapide. Seven of 9 degraded materials
      identified as ecabapide metabolites were synthesized and their antiulcer
      activities were compared with that of the parent compound. Ecabapide was potent
      to prevent gastric ulcer formation at the doses of 30-300 mg/kg i.p. Three
      metabolites (V, VIII and IX) were also active to inhibit ulceration induced by
      the stress. The antiulcer activity of IX was similar to that of ecabapide,
      whereas V and VIII had less activities. After the oral administration of
      ecabapide, the plasma levels of IX reached to less than 15% of that of ecabapide
      and also IX was largely excreted into the feces. Therefore, the potential
      implication of the metabolite (IX) as the active component in the antiulcer
      effect of ecabapide could be excluded. Furthermore, it is also unlikely that the
      high polar metabolites (IV and VII) are implicated in significant contribution
      for antiulcer action. In conclusion, we have shown that ecabapide prevents water
      immersion restraint stress-induced gastric ulcers, and that this activity is
      probably mediated by the action of the parent compound.

PMID- 7722879
TI  - [Metabolism of lomerizine hydrochloride (KB-2796) in rats].
AB  - The metabolism of lomerizine was investigated after the oral administration of
      [methine-14C] or [benzyl-14C]lomerizine hydrochloride in rats. 1. Urinary, fecal
      and biliary excretions of the unchanged drug were less than 1% of dose, showing
      that lomerizine was eliminated by the extensive biotransformation after the oral
      administration. 2. The main metabolites were 1-(2,3,4-trimethoxybenzyl)piperazine
      (M7) and 2,3-dimethoxy-4-hydroxybenzylpiperazine in the urine, and 1-[bis(4
      fuluorophenyl)methyl]-4-(2,3-dimethoxy-4-hydroxybenzyl)pi perazine in the feces
      and bile. 3. The radioactive substances in the plasma, liver and brain mainly
      existed as unconjugated forms, of which the intact drug showed the highest
      concentration. 4. The main metabolites in the plasma, and in the liver and brain
      were 1-[bis(4-fuluorophenyl)methyl]-4-(3,4-dimethoxy-2-hydroxybenzyl)pi perazine
      and bis(4-fluorophenyl)methylpiperazine (M6), respectively. 5. The plasma level
      of M7 and the biliary excretion of bis(4-fluorophenyl)-methanol in male rats were
      higher than those in female rats, suggesting the sex difference in the N
      dealkylation at the 4-position of piperazine ring of the drug.

PMID- 7722880
TI  - [Application of quantitative assay for endotoxin using immobilized histidine and
      filtration plate to parenteral drugs].
AB  - We improved the Limulus amebocyte lysate (LAL) test for endotoxins in parenteral
      drugs using immobilized histidine and a filtration plate. In order to deal with
      many samples at the same time and to apply to a routine assay, we used a
      filtration plate having 96 wells instead of a filter unit with a working volume
      of 2 ml. LAL test-affecting substances which are contained in a parenteral drug
      were separated from endotoxins by adsorbing endotoxins on immobilized histidine
      in the well of a filtration plate. Then the absorbed endotoxins were allowed to
      react with LAL reagent in the same well. We defined that this method had the
      higher precision than conventional methods and was not influenced by the
      concentrations of endotoxin and parenteral drugs. Hence we examined the recovery
      of endotoxin spiked to 23 kinds of parenteral drugs by this method, as a result,
      100 +/- 25% of recovery was obtained from 17 kinds of them.

PMID- 7722881
TI  - [Tannins, a new family of bio-active natural organic compounds (questions and
      answers)].
AB  - Twelve questions concerning tannin selected from questions raised by other
      workers on the author's research were picked up. The answers of each question are
      as follows. 1. What is tannin?--the differences between the old concept and the
      new definition of tannin. 2. Is tannic acid the same as tannin? 3. How could each
      tannin be analyzed as a pure compound? 4. Which tannin found in recent years is
      implicated with the change of the concept of tannin in medicinal plants? 5. Is it
      possible that one to several chemical structures represent tannins contained in
      each plant species? 6. Which tannin-containing plants met in the human life are
      rich in tannins? 7. Is tannin produced by all species of plants?--a correlation
      between the occurrence of hydrolyzable tannins and the plant evolution system. 8.
      When and where are the hydrolyzable tannin oligomers produced, in the plant or
      after extraction? 9. Are tannins bound to other substances in the plants? 10. Is
      it appropriate to call tannins "plant polyphenols"? 11. Is it true that tannins
      are inhibitors of enzymes? 12. What kind of biological activities have been found
      for tannins.

PMID- 7722882
TI  - Pesticides: a review article.
AB  - The use of a wide range of chemicals to destroy pests and weeds is an important
      aspect of agricultural practice in both developed and developing countries.
      Undoubtedly, this has increased crop yield and reduced postharvest losses.
      However, the expanded use of such pesticides expectedly results in residues in
      foods, which has led to widespread concern over the potential adverse effects of
      these chemicals on human health. It is clear that the possibility for exposure to
      pesticides is greatest among farm workers. Also, it is exceedingly plausible that
      less controlled and regulated uses of pesticides may offer the greatest
      opportunity for exposure to toxicologically significant quantities. Very limited
      epidemiological data are available for evaluation of the health effects of
      pesticides on humans. Only a small proportion of a population is likely to
      receive a pesticide dose high enough to cause acute severe effects; however, many
      more may be at risk of developing chronic effects (such as cancer, adverse
      reproductive outcome, and immunological effects) depending on the type of
      pesticide they are exposed to. The pesticides currently in use include a wide
      variety of chemicals with great differences in their mode of action, uptake by
      the body, metabolism, elimination from the body, and toxicity to humans. With
      pesticides that have a highly acute toxicity but are readily metabolized and
      eliminated, the main hazard lies in acute, short-term exposures. With others that
      have a lower acute toxicity but show a strong tendency to accumulate in the body,
      the main hazard is connected with long-term exposure, even to comparatively small
      doses. Other pesticides that are rapidly eliminated but induce persistent
      biological effects also present a hazard connected with long-term, low-dose
      exposures. Adverse effects may be caused not only by the active ingredients and
      the associated impurities, but also by solvents, carriers, emulsifiers, and other
      constituents of the formulated product. This review attempts to describe several
      aspects of the problem.

PMID- 7722883
TI  - Effect of a mixture of 15 commonly used pesticides on DNA levels of 8-hydroxy-2
      deoxyguanosine and xenobiotic metabolizing enzymes in rat liver.
AB  - The level of 8-OH-2-deoxyguanosine in rat liver DNA was measured as an index of
      oxidative damage after treating rats for 10 days at a dose ranging from 0.75 to
      10 mg/kg with a mixture of 15 pesticides (dithiocarbamate, benomyl,
      thiabendazole, diphenylamine, chlorthalonil, procimidone, methidathion,
      chlorpyrifos-ethyl, fenarimol, parathion-methyl, chlorpropham, parathion,
      vinclozolin, chlorfenvinphos, pirimiphos-ethyl) commonly found in foods of
      central Italy. At the doses of 0.75 and 1 mg/kg DNA levels of 8-OH-2
      deoxyguanosine were significantly increased relative to controls, whereas at
      higher doses (2.5, 5, 10 mg/kg) the levels returned to control values. The
      administration of the pesticide mixture dose dependently reduced benzo(a)pyrene
      hydroxylase, N-demethylase activities, glutathione peroxidase, glutathione
      reductase, glutathione-S-transferase and thiol transferase activities in the
      liver. The results show that the pesticide mixture induced free radical DNA
      damage at low doses. However, at higher doses it produced a depression of
      cellular metabolism, inhibiting a further expression of oxidative damage.

PMID- 7722884
TI  - An epidemiological and toxicological evaluation of the carcinogenicity of man
      made vitreous fiber, with a consideration of coexposures.
AB  - Exposure to man-made mineral (or vitreous) fiber (MMMF or MMVF) is a potential
      health concern in both occupational and environmental settings. Previous
      epidemiologic studies have reported a small increase of lung cancer among workers
      exposed to MMVF. Most of these studies were cohort studies and lacked information
      on fiber concentration, occupational coexposures, and cigarette smoking. Some of
      the coexposures were known human lung carcinogens and could have accounted for
      the small lung cancer excess. In a recently completed epidemiologic case-control
      study of lung cancer in MMVF workers exposed to slag wool fibers, we analyzed
      lung cancer risk in relation to cumulative fiber exposure (concentration and
      duration) and smoking history and controlled for other coexposures such as
      asbestos contamination. No increased lung cancer risk with exposure to slag wool
      fibers was found. As expected, however, we detected a strong confounding effect
      of smoking. The findings from this epidemiologic study were consistent with the
      results of recently completed toxicologic studies, which found that slag wool
      fibers of dimension classically associated with tumor induction ("Stanton"
      fibers) do not stay in the lung in sufficient quantity or time to induce tumors
      in animals. In this paper we emphasize the importance of confounding effects due
      to coexposures and provide guidelines to estimate the magnitude of potential
      confounding effects of coexposures such as smoking.

PMID- 7722886
TI  - Specific overexpression of P53 in sarcoma derived from Rat-1 cells transformed by
      cigarette smoking condensate-treated human fetal lung DNA.
AB  - The p53 protein is highly expressed in fibrosarcoma derived from Rat-1 cells
      transfected with cigarette smoke condensate-treated human fetal lung DNA but
      expressed low in the counterparts of nitroso-N-methylurea and dimethyl sulfoxide
      groups. Our results denoted that a high expression of p53 protein specifically
      contributes to the initiation of human lung carcinogenesis induced by cigarette
      smoke condensate. High expression and missense mutation of p53 may probably be a
      potential biomarker of initiation of human lung carcinogenesis.

PMID- 7722885
TI  - A pilot study on polychlorinated biphenyl levels in the bone marrow of healthy
      individuals and leukemia patients.
AB  - In this pilot study the concentrations of polychlorinated biphenyls (PCBs) was
      determined by capillary column gas chromatography in bone marrow from 29 adults.
      The highest concentration in all adult individuals was detected for PCB no. 180
      (mean = 0.991) followed by two other highly chlorinated PCBs, no. 153 (mean =
      0.918) and no. 138 (mean = 0.927). The less chlorinated PCBs, no. 101 (mean =
      0.255), no. 52 (mean = 0.161), and no. 28 (mean = 0.324) contributed to a lesser
      extent. Additional samples from children (N = 19) were used to assess the
      dependence of PCB concentrations on patient age (Scheele et al. Eur J Pediatr
      1992; 151:802-805). When comparing the data of adult leukemia and lymphoma
      patients with a reference group of healthy adult individuals, no significant
      increase in the leukemia patients was found.

PMID- 7722887
TI  - Difference in histology and size in colonic tumors of rats receiving two
      different carcinogens.
AB  - We investigated the histologic phenotype of experimentally induced colonic tumors
      in 412 rats: 300 Sprague-Dawley rats (treated with dimethylhydrazine = DMH) and
      112 F-344 rats (treated with glutamic acid pyrolysate = Glu). Of the 300 DMH
      treated Sprague-Dawley rats, 278 (92.6%) developed a total of 358 colonic tumors:
      60 adenomas and 298 invasive adenocarcinomas. Of the 60 adenomas, 45 (75.0%) were
      exophytic adenomas and the remaining 15 (25.0%) were flat adenomas. Of the 298
      adenocarcinomas, 82 (27.5%) were exophytic adenocarcinomas arising in exophytic
      adenomas, 39 (13%) were flat adenocarcinomas originating in flat adenomas (n =
      38) or intramucosal (n = 1), 90 (30.2%) were lymphoid-associated adenocarcinomas
      (LAC), arising in lymphoid-associated mucosa, and the remaining 87 (29.2%) were
      overt adenocarcinomas (usually signet-ring cell type carcinomas). In contrast,
      among the 112 Glu-treated F-144 rats, 62 (55.3%) developed a total of 63 colonic
      tumors: 52 adenomas and 11 adenocarcinomas. All 52 adenomas were exophytic
      adenomas and all 11 adenocarcinomas were exophytic tumors originating in
      exophytic adenomas. No flat neoplastic lesions or LAC were found. Glu-tumors were
      located predominantly in the cecum and in the right colon and were either tubular
      adenomas or tubular adenocarcinomas. In contrast, the tumors in the cecum and in
      the right colon in DMH-treated rats were usually LAC of signet-ring cell type.
      Neither flat adenomatous lesions (flat adenomas or flat adenocarcinomas) nor LAC
      were recorded in F-344 rats treated with Glu. The colonic adenomas found in the F
      344 rats attained a huge size (when compared with those seen in DMH-treated
      rats). While the cause(s) of the difference in the histologic phenotypes and
      their localization as well as of the difference in the size of the tumors between
      the two experimental groups remains unclear, it is conceivable that Glu binds,
      mutates, suppresses, or interacts with oncogenes in colonic epithelial cells in a
      different fashion than DMH. A review of the literature indicates that the genetic
      differences in the two strains of rats used in the present work may not account
      for the difference in the results obtained.

PMID- 7722888
TI  - Effects of vitamins and methionine on blastogenic response of splenocytes and
      lipid peroxidation in lung and liver of mice exposed to SiO2 dust.
AB  - We studied the effects of nutrients such as vitamin C, E, B6, niacin, and
      methionine on the blastogenic response of splenocytes and lipid peroxidation
      (LPO) in lung and liver of mice exposed to SiO2 dust. The results showed that
      after treatment with SiO2, the blastogenic response of splenocytes decreased
      significantly (p < 0.001), whereas the LPO level in lung and liver increased
      remarkably (lung p < 0.05; liver p < 0.001). Vitamin E, C, and niacin strongly
      enhanced the blastogenic response of T and B splenic lymphocytes to concanavalin
      A and to lipopolysaccharide (p < 0.001). The effects of methionine and B6 were
      much less intense. Other supplied nutrients have been shown to inhibit LPO in
      lung and liver of mice exposed to SiO2 (p < 0.001).

PMID- 7722889
TI  - Effects of dietary supplementation on the function of alveolar macrophages of
      silicosis rats, on the blastogenic response of lymphocytes and on the peroxidase
      activity in blood of silicosis patients.
AB  - We studied the effects of a nutrient supplemented diet on the function of
      alveolar macrophages of silicosis rats and on the blastogenic response of
      lymphocytes, glutathione peroxidase (GSH-PX) activity, and lipid peroxidase (LPO)
      activity in the blood of silicosis patients. The results showed that a nutrient
      supplemented diet increased the phagocytosis rate (p < 0.01) and index (p < 0.05)
      of alveolar macrophages of silicosis rats. A nutrient supplemented diet also
      enhanced significantly the GSH-PX activity (p < 0.001) and the blastogenic
      response of lymphocytes (p < 0.01), and decreased substantially the LPO content
      (p < 0.05) in the blood of silicosis patients. We conclude that a nutrient
      supplemented diet may play an important role in antilipid peroxidation, decreased
      free radical reaction, stabilizing cell membrane, delaying lung fibrosis, and
      enhancing immune functions of the body.

PMID- 7722890
TI  - Subconjunctival anesthesia in cataract surgery.
AB  - This article reports the results of using subconjunctival anesthesia (SCA) in
      cataract surgery. Subjective patient questionnaires and the medical records of
      133 consecutive SCA patients who had scleral tunnel phacoemulsification cataract
      surgery were analyzed. All SCA patients received preoperative medication, but
      most (77%) received no intraoperative medication. Most patients who had SCA (90%)
      reported no pain during surgery. The most common postoperative complaints were
      pain, patching, and headache. Uncorrected visual acuity, tested a mean time of 35
      minutes after surgery, was 20/200 or better in 69% of the SCA patients.
      Subconjunctival anesthesia provided a safe, effective, and minimally invasive
      technique.

PMID- 7722891
TI  - Vacuum capsulorhexis.
AB  - A new method of performing continuous curvilinear capsulorhexis is described. It
      involves the use of a fine point of suction applied to the torn flap of anterior
      capsule through a fine cannula. This technique offers excellent control of the
      tear and requires no viscoelastic to maintain the anterior chamber. Only a few
      inexpensive hand instruments are needed to perform the technique, which is easily
      learned.

PMID- 7722892
TI  - Topical anesthesia using the Bloomberg SuperNumb Anesthetic Ring.
AB  - Advances in phacoemulsification and self-sealing wound construction have made
      topical anesthesia an effective and reliable method of obtaining ocular
      anesthesia. It has many advantages over the traditional retrobulbar or peribulbar
      technique. I have performed more than 1800 cases of phacoemulsification and
      posterior chamber intraocular lens implantation through a 3 mm, self-sealing,
      corneal tunnel incision with topical anesthesia and the use of the Bloomberg
      SuperNumb Anesthetic Ring. This article presents the procedure. Results show the
      benefits of topical anesthesia and the anesthetic ring, including elimination of
      the risks of globe penetration, retrobulbar hemorrhage, respiratory depression,
      intradural or subarachnoid injection, ptosis, and diplopia, as well as instant
      return of vision.

PMID- 7722893
TI  - Prevalence of central islands after excimer laser refractive surgery.
AB  - We conducted a study to determine the prevalence of central islands after
      refractive excimer laser surgery and the factors associated with their
      occurrence. A VISX Twenty/Twenty excimer laser was used to perform 157
      photorefractive keratectomy (PRK) and 263 photorefractive astigmatic keratectomy
      (PARK) procedures. Corneal topography was assessed in 156 patients three months
      postoperatively using a topographic analysis system. Central islands were seen in
      67% of patients; 26% had islands of 3.0 diopters (D) or more in height.
      Occurrence was associated with the laser suction nozzle being fixed during the
      procedure (P < .05). There was no demonstrable effect of central islands on
      visual acuity or refractive outcome, nor was there any relation to the amount of
      attempted correction or type of procedure (PARK or PRK). Central islands with a
      curvature difference of less than 3.0 D were seen more frequently than an absence
      of islands, suggesting these may be a "normal" postoperative topographic
      variation. The effect of nozzle position on island formation suggests that plume
      removal or corneal hydration may be important, as is corneal epithelial healing.

PMID- 7722894
TI  - Minimally invasive radial keratotomy: mini-RK.
AB  - Radial keratotomy (RK) is a common surgical technique for correcting myopia. The
      RK incisions, like any corneal incisions, permanently weaken the cornea and this
      structural weakening can cause several complications and side effects, including
      diurnal fluctuation, progressive hyperopic shift, and the potential for traumatic
      rupture of the keratotomy scars. I describe a new technique--minimally invasive
      RK (mini-RK)--that reduces the millimeters of cornea incised and present
      preliminary laboratory and clinical results. In a cadaver eye study, eight short,
      deep incisions extending from the 3.0 mm optical zone to the 7.0 mm optical zone
      produced 92% of the efficacy of full-length incisions to the 11.0 mm optical
      zone. This finding was confirmed by intraoperative surgical keratometry in six
      patients in whom a 1% increase in central corneal flattening was achieved when
      incisions were extended from the mini-RK configurations to full length. In a
      retrospective evaluation of 100 patients with -1.0 to -6.0 diopters (D) of
      myopia, 92% of eyes were within 1.0 D of emmetropia and 94% had 20/40 or better
      uncorrected visual acuity. No significant complications were encountered. Mini-RK
      may be a useful alternative to reduce the invasiveness of RK but retain its
      efficacy in eyes with low to moderate myopia.

PMID- 7722895
TI  - Vector analysis.

PMID- 7722896
TI  - Preferred postoperative refraction after cataract surgery for high myopia.
AB  - Eighty-four patients (121 eyes) with high myopia who had cataract surgery and
      intraocular lens implantation completed a survey on preferred postoperative
      refraction. Forty-two percent of the sample reported that they were accustomed to
      removing their glasses to read a newspaper or book. These respondents were fitted
      with soft contact lenses and their refraction changed to 0 D, -3.00 D, and -5.00
      D. Of the patients whose best corrected postoperative visual acuity was 20/40 or
      better (n = 63), 48% preferred the -3.00 D correction; 38%, the 0 D correction;
      and 14%, -5.00 D. Of those with a best corrected postoperative visual acuity
      worse than 20/200 (n = 8), 80% preferred the -5.00 D refraction, which allowed
      them to read close up. Most patients with phakic eyes and good visual acuity (n =
      13) preferred the 0 D and -3.00 D corrections. Our results indicate that in
      patients with high myopia, it is important to take patient preference into
      account when selecting postoperative refraction.

PMID- 7722897
TI  - Relative stability of clear corneal incisions in a cadaver eye model.
AB  - Three different clear corneal square incisions--beveled (or paracentesis),
      stepped, and hinged--were studied in a cadaver eye model to determine whether a
      critical width existed for each incision type at which resistance to external
      pressure changed substantially, given identical tunnel length (1.75 mm to 2.00
      mm) for each incision. As a comparison, the beveled (paracentesis) incision was
      also performed as a clear corneal incision at the anterior limbus, making it a
      limbal beveled incision. One surgeon performed all procedures. Incision width
      ranged from 2.5 mm to 5.0 mm in 0.5 mm increments. External pressure as high as
      525 psi was applied to all eyes at two ranges of intraocular pressure (10 mm Hg
      to 15 mm Hg and 20 mm Hg to 25 mm Hg) to determine the relative ability of each
      incision type to resist leakage. The hinged incision performed better than the
      stepped and corneal beveled incisions. When the beveled (paracentesis) incision
      was made as a clear corneal limbal beveled incision at the anterior limbus, the
      limbal structures provided additional support in resisting externally applied
      pressure. When the clear corneal beveled technique is used, incision width should
      be 3.0 mm or less. When clear corneal stepped or hinged techniques are used,
      incision width should be 3.5 mm or less.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722898
TI  - Peribulbar versus retrobulbar.

PMID- 7722899
TI  - Treatment of a monocular patient with an improperly implanted lens.

PMID- 7722900
TI  - Recommendation for correctly analyzing photorefractive keratectomy centration
      data.

PMID- 7722901
TI  - Prospective evaluation of surgically induced astigmatism and astigmatic
      keratotomy effects of various self-sealing small incisions.
AB  - The refractive effects of self-sealing clear corneal and corneoscleral tunnel
      incisions, 3.5 mm and 5.2 mm, in cataract surgery were studied prospectively by
      automatic keratometric evaluation at day one postoperatively and weeks one,
      three, and six. Keratometric readings were converted to polar values. The amount
      of surgically induced astigmatism was calculated for each incision and mean
      postoperative keratometric astigmatism was estimated for patients with
      preoperative against-the-rule and with-the-rule astigmatism to evaluate the
      astigmatic keratotomy effects of the incisions. The corneoscleral incisions were
      almost astigmatically neutral, with no major difference between the 3.5 mm and
      the 5.2 mm incisions after six weeks. The 5.2 mm frown incisions were less stable
      than the straight corneoscleral incisions. Clear corneal incisions resulted in a
      considerable amount of induced astigmatism; there was more with the 5.2 mm
      incisions than with the 3.5 mm incisions. Temporal incisions resulted in a with
      the-rule induced change and superior incisions, an against-the-rule induced
      change. The refractive effect of the clear corneal incisions did not change
      significantly from day one to week six. The astigmatic keratotomy effects of
      these incisions were therefore more useful and predictable. Preoperative against
      the-rule astigmatism was reduced significantly by temporally placed clear corneal
      incisions and preoperative with-the-rule astigmatism, by superiorly placed clear
      corneal incisions. If one considers the preoperative astigmatism when selecting
      incision type and location for small incision cataract surgery, one can minimize
      postoperative keratometric astigmatism.

PMID- 7722902
TI  - Long-term results of combined trabeculectomy and small incision cataract surgery.
AB  - We did a prospective study of 49 eyes (36 patients) with coexisting cataract and
      glaucoma who had combined trabeculectomy, phacoemulsification, and implantation
      of a folded polyHema intraocular lens through the trabeculectomy opening.
      Preoperatively, intraocular pressure (IOP) was controlled (< 20 mm Hg) in 13 eyes
      on a mean of 2.2 medications and uncontrolled (> 20 mm Hg) in 36 eyes on a mean
      of 2.4 medications. Preoperative visual acuity ranged from 20/40 to hand
      movements. At the end of the follow-up, IOP was below 18 mm Hg in all eyes
      (100%), without therapy in 39 (80%) and with reduced therapy in 8 (16%). Two (4%)
      eyes were controlled on the same medication regimen. Visual acuity improved in 42
      patients (86%); 38 (78%) achieved a visual acuity of 20/40 or better. A filtering
      bleb was observed in 45 eyes (92%). The most common early postoperative
      complication was fibrin exudation into the anterior chamber. Late complications
      included posterior synechias and vision-impairing capsule opacifications. Visual
      acuity improved after neodymium:YAG laser treatment in all eyes with
      opacification without further complications. We conclude that the combination of
      small incision cataract surgery and trabeculectomy is a successful surgical
      approach for long-term visual rehabilitation and glaucoma control.

PMID- 7722903
TI  - Donut wedge cataract positioner.

PMID- 7722904
TI  - Comparison of endothelial cell loss and phacoemulsification energy during
      endocapsular phacoemulsification surgery.
AB  - We counted central corneal endothelial cells and measured corneal thickness in 64
      human eyes before and three months after cataract extraction and posterior
      chamber lens implantation. Cataract surgery was the same in all patients and
      included capsulorhexis and posterior chamber phacoemulsification of the nucleus.
      Total phacoemulsification energy and time were recorded. A heparin-surface
      modified intraocular lens or a regular poly(methyl methacrylate) lens, both
      having the same design and a 5.0 mm optic, was implanted in the capsular bag with
      the aid of sodium hyaluronate (Healon). Mean endothelial cell loss was 4%.
      However, the change in cell density did not correlate with the total
      phacoemulsification energy used during surgery. Three months after surgery, the
      central corneal thickness was the same as it had been preoperatively. The results
      suggest that phacoemulsification in the posterior chamber is a safe procedure
      even in cases with a hard nucleus.

PMID- 7722905
TI  - Causes of decreased visual acuity after cataract extraction.
AB  - We analyzed a consecutive series of cataract extractions to determine the causes
      of unsuccessful results. Our criterion was a decrease in visual acuity from the
      preoperative measurement. Fourteen of 1237 eyes met this criterion. In three of
      the 14, visual acuity was decreased by more than two Snellen lines. Vitreous loss
      occurred in seven of the eyes. In six of these, cystoid macular edema developed.
      The reasons for reduced visual acuity were cystoid macular edema (eight eyes), an
      aggravation of age-related maculopathy (three eyes), and vitreous hemorrhage and
      herpetic keratitis (one eye each). A branch vein occlusion caused macular edema
      and vitreous hemorrhage in one eye. From this data, we recognize the importance
      of avoiding vitreous loss. If it does occur, we recommend that meticulous
      anterior vitrectomy be performed, with as little manipulation as possible.

PMID- 7722906
TI  - Origin of hydrodissection.

PMID- 7722907
TI  - Origin of the scleral tunnel incision.

PMID- 7722908
TI  - Surgical management of dislocated intraocular lenses.
AB  - Intraocular lens (IOL) malpositions range from simple IOL decentration to
      luxation into the posterior segment. Many surgical techniques and approaches have
      been devised to treat visually significant IOL dislocation. In this series, 78
      eyes with IOL dislocation were managed by anterior segment and vitreous surgeons
      with a variety of surgical techniques using a limbal, pars plana, or combined
      limbal-pars plana approach. Most of the dislocated lenses were posterior chamber
      IOLs. In 39 of 78 eyes (50%), final visual acuity was 20/50 or better. Neither
      surgical approach nor management technique appeared to be related to outcome. The
      timing of surgery did not appear to affect visual outcome but was not examined in
      a randomized fashion. Guidelines for determining optimal management are
      presented.

PMID- 7722909
TI  - Astigmatism after cataract surgery: nylon versus Mersilene. Five-year data.
AB  - This is a follow-up of a previous study that evaluated astigmatism after cataract
      surgery. In that study with a six-month follow-up, there was no statistically
      significant difference in astigmatism between eyes with nylon sutures and those
      with polyester fiber (Mersilene) sutures. This article reports the five-year data
      on this series of eyes.

PMID- 7722910
TI  - Efficacy of topical flurbiprofen and indomethacin in preventing pseudophakic
      cystoid macular edema. Flurbiprofen-CME Study Group I.
AB  - We evaluated two topical cyclo-oxygenase inhibitors (COIs), 0.03% flurbiprofen
      and 1% indomethacin, for their ability to prevent pseudophakic cystoid macular
      edema (CME). The study was a randomized, double-masked, vehicle-controlled,
      parallel group, clinical trial for six months at eight sites in Canada and two in
      Germany. The study population consisted of 681 patients who had extracapsular
      cataract extraction and posterior chamber lens implantation. Flurbiprofen,
      indomethacin, or the vehicle was instilled into the eye four times daily for two
      days preoperatively and three months postoperatively. Results were measured by
      angiographic and clinical CME at visit 5 (day 21-60) and visit 7 (day 121-240)
      and by contrast sensitivity and Snellen visual acuity at all five postoperative
      visits. At visit 5, the incidence of angiographic CME was comparable in the two
      COI treatment groups (16.8% flurbiprofen, 12.4% indomethacin) and was
      significantly lower than in the vehicle group (32.2%). The incidence of clinical
      CME was also significantly lower in the COI-treated groups (10.7% flurbiprofen,
      9.6% indomethacin) than in the vehicle group (21.9%). By visit 7, the incidence
      of angiographic CME had declined to between 4% and 8% and the incidence of
      clinical CME was less than 2% in all three groups. At visit 5, contrast
      sensitivity scores were significantly worse in vehicle-treated patients with
      angiographic CME than in those without CME, and Snellen visual acuity was one
      line worse in patients with CME. Flurbiprofen-treated patients achieved good
      Snellen visual acuity (better than 20/40) sooner than vehicle-treated
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722911
TI  - Consultation section. Contact-lens-intolerant.

PMID- 7722912
TI  - Effects of flurbiprofen and indomethacin on acute cystoid macular edema after
      cataract surgery: functional vision and contrast sensitivity.
AB  - We examined the effect of acute cystoid macular edema (CME) on contrast
      sensitivity. Eyedrops were instilled into the surgically treated eye f1p4 times
      daily for two days preoperatively and for three months postoperatively.
      Angiographic and clinical CME were measured, as were contrast sensitivity and
      Snellen acuity. Jaeger visual acuity equivalents were calculated and digital
      imaging techniques used to simulate visual function. We found that angiographic
      CME reduces functional vision as measured by contrast sensitivity and visual
      acuity over a large range of sizes. In patients treated with the flurbiprofen
      vehicle, those without CME had higher mean contrast sensitivity scores than those
      with CME; this increased over time. Those treated with flurbiprofen and
      indomethacin had slightly higher contrast sensitivity scores than vehicle-treated
      patients; this also increased over time, most notably in the higher spatial
      frequencies. Flurbiprofen treatment improved contrast sensitivity in patients
      with and without CME significantly at 12 cycles per degree. Flurbiprofen-treated
      patients with CME in general had higher contrast sensitivity scores than vehicle
      treated patients. In this population of patients having cataract surgery,
      treatment with flurbiprofen or indomethacin reduced the loss of functional vision
      associated with CME.

PMID- 7722913
TI  - Long-term results of surgical treatment of high myopia with Worst-Fechner
      intraocular lenses.
AB  - This retrospective study evaluated the results in 90 eyes that had a minuspower
      anterior chamber intraocular lens implanted to correct high myopia. Preoperative
      myopia ranged from -7.00 to -24.00 D. Postoperative spherical equivalent was 
      0.50 D; 80.5% of eyes were within 1.00 D of emmetropia. Two years
      postoperatively, no cataract formation, retinal detachment, glaucoma, or
      significant endothelial damage had occurred. We conclude that minus-power lenses
      can rapidly, safely, and predictably correct high myopia in phakic patients.

PMID- 7722914
TI  - Effect of intraocular lens size on posterior capsule opacification after
      phacoemulsification.
AB  - Posterior capsule opacification (PCO) is one of the most common complications of
      phacoemulsification with intraocular lens (IOL) implantation. This retrospective
      study evaluated the incidence of neodymium: YAG (Nd:YAG) laser capsulotomies for
      PCO in two groups of patients with different sizes of poly(methyl methacrylate)
      (PMMA), capsular bag-fixated IOLs. We evaluated 437 eyes that had
      phacoemulsification with continuous curvilinear capsulorhexis over a four-year
      period. Patients were placed in one of two groups, based on IOL size: large IOL
      (lens length 13.5 mm or greater) and small IOL (lens length less than 13.5 mm).
      In the large IOL group, 106 of 280 patients (38%) required YAG laser posterior
      capsulotomy; in the small IOL group, 25 of 157 patients (16%) did. This
      difference was statistically significant even though the average follow-up was
      84.1 weeks in the large IOL group and 54.1 weeks in the small IOL group.

PMID- 7722915
TI  - Heat shock protein expression in oral lichen planus.
AB  - To assess the potential role of heat shock protein (HSP) in the pathogenesis of
      oral lichen planus (OLP), sections of OLP, normal oral mucosa, non-specific oral
      ulceration (NSOU) and dysplastic OLP were assessed for HSP expression using
      avidin-biotin complex immunohistochemistry with an anti-HSP 70 polyclonal
      antibody. There were statistically significant differences in both the vertical
      and horizontal staining distribution when other groups were compared with the OLP
      group (p < 0.01). Using microdensitometry, the mean staining intensity in OLP,
      dysplastic OLP and NSOU was elevated in comparison with normal oral mucosa (p <
      0.001). In a standard tritiated thymidine uptake assay, lymphocytes extracted
      from nine OLP lesions demonstrated significant proliferation when stimulated with
      purified protein derivative (PPD), of which HSP is a major constituent, with
      stimulation indices ranging from 2 to 132. These results are consistent with the
      hypothesis that, in OLP patients, diverse exogenous agents may cause upregulated
      expression of HSP by oral mucosal keratinocytes. A reaction of cytotoxic T
      lymphocytes to these activated keratinocytes may then result in the tissue
      destruction which is characteristic of OLP lesions.

PMID- 7722916
TI  - Cytomegalovirus (CMV) and Helicobacter pylori (HP) found in oral mucosal ulcers.
AB  - The possible involvement of Cytomegalovirus (CMV) and Helicobacter pylori (HP) in
      oral mucosal ulcers is suggested by their role in the development of ulceration
      at other mucosal sites of the gastrointestinal tract. A series of 29 incisional
      biopsies from 29 consecutive and apparently immunocompetent patients attending
      the clinic for oral ulceration were examined by routine histopathology as well as
      by in situ hybridisation (ISH) with biotinylated CMV and HP DNA probes. In 14/29
      biopsies, Giemsa staining disclosed spiral bacteria. Six (20.7%) of these 14
      Giemsa-positive samples showed HP DNA on ISH and 3 ulcers (10.3%) contained CMV
      DNA. In none of the specimens were CMV and HP detected simultaneously. Two of the
      ulcers containing CMV DNA were found on the labial mucosa and one on the
      posterior palatal mucosa, whereas all HP DNA-positive ulcers were located on the
      buccal mucosa. The results indicate that CMV and HP DNA can be found in separate
      oral mucosal ulcers in apparently immunocompetent adults.

PMID- 7722917
TI  - p53 protein expression in sequential biopsies of oral dysplasias and in situ
      carcinomas.
AB  - Immunohistochemically detectable levels of p53 may be seen early in the malignant
      transformation of some neoplasms. To determine if p53 is immunocytochemically
      detectable, and therefore presumptively abnormal, in oral dysplasias and in situ
      carcinomas, and to explore the natural history of p53 protein expression in these
      lesions, sequential biopsies from patients with lesions occurring in the same
      anatomic site were examined. Formalin-fixed, paraffin-embedded sections from 19
      patients were evaluated immunohistochemically for p53 protein using antibody
      clones Pab1801 and BP53-12. With two exceptions, comparable results were observed
      with these antibodies. p53 protein was detected immunocytochemically in 6 of 13
      patients with dysplasias; 3 of these progressed to p53-positive invasive
      carcinoma, one advanced to a more severe grade of p53-positive dysplasia, one
      developed into a p53-negative verrucous carcinoma, and one represented a p53
      positive dysplasia developing five years after treatment of a p53-positive
      carcinoma. The p53-positive dysplasias, which were found in all subtypes (mild,
      moderate, severe), preceded histologic malignant change by months to years. p53
      detection was evident in 4 of 6 patients with in situ lesions. Sequential
      biopsies of three of these lesions showed no change in lesion histology or p53
      staining, and one lesion advanced to a p53-positive carcinoma. It is concluded
      that p53 protein may be detected early in the development of a subset of p53
      positive oral squamous cell carcinomas. This phenomenon may be seen in dysplasias
      and in situ lesions, and it may have prognostic implications.

PMID- 7722918
TI  - Biotypes of oral Candida albicans isolates in human immunodeficiency virus
      infected patients from diverse geographic locations.
AB  - Oral Candida albicans isolates from HIV-infected individuals in Hong Kong,
      Australia, Germany and England were characterised using a biotyping system based
      on enzyme profiles, carbohydrate assimilation patterns and boric acid resistance
      of the yeasts. A total of 44 biotypes were found amongst the 117 oral C. albicans
      isolates examined. The major biotype A1R accounted for 17.9% of all isolates
      while the second commonest biotype was A1S (11.1% of isolates). Whereas these two
      biotypes were isolated from all the regions studied, there were a number of other
      biotypes unique to individual countries. The data indicate that there are many
      different sub-strains of oral C. albicans in HIV-infected patients, some of which
      are globally prevalent. However, further work is required to ascertain the
      diversity of oral C. albicans biotypes, if any, in health and disease.

PMID- 7722919
TI  - Changes in nerve fibers adjacent to transplanted VX2 carcinoma in rabbit tongue.
AB  - This study was undertaken to examine the relationship between malignant tumor
      tissue and nerve fibers using a transplantation model and nerve fiber strains.
      Most of the neural tissue, as well as the other host tissues, showed severe
      degenerative changes as the transplanted tumor grew. Furthermore, the
      degenerative changes were chiefly confined to the area anterior to the tumor.
      These changes were probably provoked chiefly by the compressive effects of the
      rapidly enlarging transplant. The results could possibly explain clinical
      symptoms such as paralysis or disturbances in the movement of the tongue observed
      occasionally in some patients with lingual carcinomas.

PMID- 7722920
TI  - Oral psoriasis: report of six new cases.
AB  - This article presents six cases of oral psoriasis originally diagnosed by means
      of the histological changes found on biopsies of the oral lesions. Three of the
      patients presented with oral and skin psoriasis. Of the remaining three, two
      presented with oral manifestations alone, although their follow-up was short,
      whilst the third showed delayed dermatological changes. Two of the cases were
      also complicated by psoriatic arthritis, one of them to the temporomandibular
      joint.

PMID- 7722921
TI  - An association between recurrent oro-genital ulceration and non-steroidal anti
      inflammatory drugs.
AB  - Recurrent oro-genital ulceration is a common condition of unknown aetiology. This
      paper describes a patient who had severe recurrent oro-genital ulceration which
      was unresponsive to conventional therapy. The patient was taking non-steroidal
      anti-inflammatory drugs (NSAIDs) prescribed for osteoarthritis. When she stopped
      this medication, she had no further genital ulceration and the pattern of her
      oral ulceration was dramatically improved. There have been no previously reported
      cases of recurrent oro-genital ulceration associated with NSAIDs.

PMID- 7722922
TI  - Characteristics of the oral lesions in patients with cutaneous recurrent erythema
      multiforme.
AB  - Erythema multiforme may be recurrent and the oral cavity is often affected. A
      series of 82 patients with unequivocal recurrent cutaneous erythema multiforme
      were examined to determine the incidence and nature of oral lesions. Seventy per
      cent of patients had oral lesions, comprising multiple, large, shallow, extremely
      painful and debilitating ulcers, which affected the entire oral mucosa in over
      20%. The buccal mucosa and tongue were the most frequently affected sites in the
      remainder and the lips were affected in 13% of patients. Lesions generally lasted
      for 1-3 weeks. In over 60% of cases these attacks followed an episode of herpes
      simplex virus infection during the preceding fortnight. Recurrent attacks showed
      a different site distribution from the initial attacks, with a greater proportion
      having genital as well as skin and oral mucosal involvement. Detailed case
      histories of five patients are presented to illustrate the role of azathioprine
      in treating oral lesions and to document a familial case of recurrent erythema
      multiforme, with severe mucosal involvement.

PMID- 7722923
TI  - Implications of congenitally missing teeth: orthodontic and restorative
      procedures in the adult patient.
AB  - Missing teeth are a concern to the patient and restorative dentist, and this
      social liability can be a multifactorial problem that involves esthetics,
      phonetics, disease, function, and stabilization. Dental caries, trauma, and
      periodontal disease are usually identified by pain, food impaction, discomfort,
      and lack of esthetics or poor phonetics. Restorative dentists are concerned with
      all aspects of the general health and appearance of the stomatognathic system and
      not only have the responsibility for immediate correction of an extant problem,
      but also for ensuring long-term "outcomes." The perceptive integration of
      interspecialty orthodontic treatment before restorative dentistry can obviate
      deleterious circumstances that threaten successful completion of the treatment
      plan. The prerestorative repositioning of malposed adjacent teeth in spaces
      created by congenitally missing teeth is illustrated with clinical treatment of
      three patients.

PMID- 7722924
TI  - Temperature increase during removal of incisal extensions on resin-bonded
      castings.
AB  - To assist seating or relocation of resin-bonded retainers on abutments,
      extensions of the cast framework can be incorporated and removed after
      cementation. There has been apprehension concerning the heat created during the
      grinding of these extensions, particularly if there is a substantial bulk of
      metal. This study recorded the elevation of temperature when cast incisal
      extensions were removed by grinding after cementation. A total of 20 retainers
      were waxed for 0.3 mm thickness, cast in a nickel-chrome alloy, and bonded in
      vitro to an acid-etched natural tooth with composite resin cement. The
      temperature of the coronal dentin was measured while the tag was ground with a
      high-speed dental handpiece. The maximum temperature and mean temperature
      elevations that exceeded the resting temperature were recorded. A significant
      temperature rise was apparent when complete incisal wrapover framework extensions
      were reduced compared with the removal of fingerlike locating extensions. In
      conclusion, care should be exercised when the locating extensions of resin-bonded
      retainers are removed with high-speed dental handpieces.

PMID- 7722925
TI  - Expansion of phosphate-bonded investments: Part II--Thermal expansion.
AB  - This study investigated the thermal expansion of phosphate-bonded investment
      materials. Three investments were mixed with either distilled water or their
      special liquids and allowed a setting time of 1 or 24 hours. Hydration and
      thermal expansions were measured with a vertical dilatometer and were analyzed
      for interactive and main effects. The amount of expansion attributed to hydration
      was minimal, whereas thermal expansions varied and were of greater magnitudes.
      Material I exhibited the greatest thermal expansion. Materials II and III
      recorded smaller thermal expansions that increased when the materials were mixed
      with their special liquids. Setting time did not substantially influence
      hydration expansions but did influence thermal expansions, and heating the
      materials to 800 degrees C instead of 700 degrees C did not dramatically elevate
      expansions.

PMID- 7722926
TI  - Oral findings in elderly nursing home residents in selected countries: quality of
      and satisfaction with complete dentures.
AB  - A total of 249 complete denture wearers were examined from a geriatric population
      of 610 patients in seven institutions in four different countries. The evaluation
      of denture quality was made by the patients' opinions and the examiners rankings
      with a questionnaire on interocclusal distance, occlusal function, extension,
      stability, comfort, and esthetics of the dentures. At each of the surveyed
      institutions, the patients consistently considered their dentures better than did
      the examiners and the maxillary dentures were rated better that the mandibular
      dentures by the clinicians and by the patients.

PMID- 7722927
TI  - Oral findings in elderly nursing home residents in selected countries: oral
      hygiene conditions and plaque accumulation on denture surfaces.
AB  - Many removable-denture wearers do not keep their prostheses clean. One result of
      poor hygiene is the accumulation of plaque and/or food debris on the denture
      surfaces, the oral tissues, the residual ridges, palate, cheeks, and tongue. In
      the study of the oral conditions of geriatric patients living in institutions,
      610 patients were examined in seven old-age homes in four different countries:
      the United States, Peru, Argentina, and Israel.

PMID- 7722928
TI  - The dietary adequacy of edentulous older adults.
AB  - This study tested the null hypothesis that there are no differences in dietary
      patterns or adequacy between edentulous patients and individuals with nearly
      complete dentitions. The research design involved comparing the dietary patterns
      and adequacies of 34 edentulous subjects who regularly wear dentures with 38
      subjects who had nearly complete dentitions. The subjects were between the ages
      of 51 and 83 years and were sampled from patients attending Case Western Reserve
      University Dental Clinic. Although edentulous subjects were more likely to claim
      that they had trouble chewing their food, they were not more likely to select
      easy-to-chew foods. On the other hand, the diet of dentate subjects tended to be
      superior to that of edentulous subjects, as indicated by a lower fat and
      cholesterol consumption and a higher consumption of protein and all of the
      vitamins and minerals (significantly or nearly significantly for vitamin A,
      ascorbic acid, calcium, and riboflavin).

PMID- 7722929
TI  - Neuropathic implications of prosthodontic treatment.
AB  - Associated with prosthodontic procedures, there may be the development of a
      chronic pain state caused by injury to peripheral branches of the trigeminal
      nerve. Neuropathic pains have not been discussed in the prosthodontic literature
      and yet are becoming increasingly common, especially in relation to the placement
      of implant prostheses. This article reviews the pathophysiologic and clinical
      features associated with neuropathic pain after dental procedures (traumatic
      neuralgia). The prosthodontist should become aware of neuropathic pain as a
      possible complication of treatment and informed consent should be obtained before
      procedures are started that might damage nervous tissue.

PMID- 7722930
TI  - Conventional linear tomography: protocol for assessing endosseous implant sites.
AB  - Proper implant dimension and implant site selection are two major factors that
      affect the eventual prosthodontic rehabilitation and long-term serviceability of
      the implant and prosthesis. Conventional linear tomography permits accurate
      measurements and assessment of available bone for both factors. A protocol for
      the use of conventional linear tomography for diagnostic assessment, evaluation
      of proposed implant sites, and the selection of proper implant type and dimension
      is presented.

PMID- 7722931
TI  - A multiple tray technique for implant-retained orbital prostheses.
AB  - The use of implants in retaining orbital prostheses has gained favor in recent
      years. Not all patients may be candidates for use of medical adhesives or
      anatomic retention as advocated by some. Osseointegrated implants offer an
      alternative method for retaining an orbital prosthesis. Because of the confining
      nature of an orbital defect, it may be difficult to reproduce the spatial
      arrangement of implants accurately with one impression. The technique presented
      here accomplishes the objectives of minimal trauma to the tissues, accuracy, and
      elimination of consecutive impression technique.

PMID- 7722932
TI  - Freestanding magnetic retention for extraoral prosthesis with osseointegrated
      implants.
AB  - Implant-retained articular prostheses have commonly had clips or magnets in
      conjunction with a rigid bar splint. New-generation magnets and associated
      abutment magnetic caps now provide for free standing magnetic retention that is
      secure and provides improved abutment access for the patient because the bar is
      absent.

PMID- 7722933
TI  - Technique for magnet replacement in silicone facial prostheses.
AB  - Magnets are often used in silicone facial prostheses for retention. However,
      these magnets may need to be replaced or repositioned as a result of loss, wear,
      or poor initial placement. Replacement can be easily accomplished by use of a
      nylon mesh material and a simple laboratory technique.

PMID- 7722934
TI  - A rationale for a simplified occlusal design in restorative dentistry: historical
      review and clinical guidelines.
AB  - An occlusal contact pattern in which the number of occlusal contacts has been
      substantially reduced as compared with traditional schemes is described. Concepts
      that may have had a justification in balanced occlusions have been needlessly
      transferred to anterior disclusion mechanics. No natural dentition presents
      occlusal contacts as described in many texts and yet stability is established.
      The temporomandibular joint does present structural changes that should be
      accounted for when an occlusal anatomy is designed. The force vectors that are
      active on teeth are not directed along the longitudinal axes of the roots only,
      and thus occlusal contact locations will not determine the direction of
      functional forces. The stability of the teeth on the arch depends primarily on
      the forces of eruption from the periodontium and the balance between the resting
      pressures of the muscles of the cheeks and the tongue. The mechanics of the
      stomatognathic system are not as accurate as their counterpart on an articulator.
      The variability of the guiding surfaces inherent to the temporomandibular joints
      should be incorporated into an occlusal design. Occlusal contacts that do not
      fulfill a justifiable purpose may be eliminated, and the number of contacts may
      be reduced to one per tooth.

PMID- 7722935
TI  - Reliability of a portable electromyographic unit to measure bruxism.
AB  - This study evaluated the effect of different rates of increase of occlusal force
      and of removal and replacement of the electromyographic electrodes on the amount
      of occlusal force needed to trigger a modified electromyographic measuring unit.
      Seven subjects placed the electrodes on the masseter area on one side, and bit
      ipsilaterally on a bite force transducer. The electromyographic recorder was
      adjusted to be triggered only when the subject clenched. Occlusal force was
      recorded simultaneously with triggering of the electromyographic recorder. The
      subjects performed two series of five repetitions of clenching at each of four
      different rates of increase of force, by visual feedback from a second
      oscilloscope until the electromyographic recorder was triggered, and an occlusal
      force measurement was made from the first oscilloscope. Repeated measures of
      ANOVA analysis revealed no statistically significant differences among the
      different rates of increase in occlusal force or between the two recording
      series. Interaction between the two factors also was not significant. The
      intraclass correlation coefficient was large and statistically significant,
      indicating that this device was reliable for this method.

PMID- 7722936
TI  - Clinical study of location and reproducibility of three mandibular positions in
      relation to body posture and muscle function.
AB  - Clinical studies have confirmed the adequate reproducibility of both centric
      occlusion and centric relation when used as reference positions during treatment;
      however, the reproducibility of the neuromuscular position has been found
      inadequate. This study evaluated the location and reproducibility of these three
      mandibular positions in relation to body posture, sitting and supine, and
      bilateral muscle activity before and after the insertion of a flat mandibular
      positioning device equilibrated to balance the muscle functions, as shown by two
      electromyography biofeedback instruments. Intraoral recordings were made in 11
      young subjects with complete natural dentition. Acrylic resin clutches that
      supported a screw point in the maxillary arch and painted glass in the mandibular
      arch were used and positioned not to interfere with the occlusion. The distances
      of the screw scratch from two of the edges of the painted glass were used to
      measure the anteroposterior and mediolateral locations with a micrometer. The
      reproducibility was evaluated by measuring the scratch surface by measuring the
      weight of the print cutouts made from photographs of the scratches taken with a
      stereoscope. The location and reproducibility of centric occlusion and centric
      relation were not affected by body posture. A more precise posterior
      neuromuscular position was obtained in the supine position. The insertion of a
      mandibular positioning device did not affect centric occlusion but gave a more
      precise centric relation. Neuromuscular position became as precise as centric
      occlusion and was located anteroposteriorly between centric occlusion and centric
      relation.

PMID- 7722937
TI  - Amalgam restoration and in vitro caries formation.
AB  - Black's class I classic cavity preparations were completed in 124 extracted
      intact human premolars, of which 120 were restored with one of two silver
      amalgams, five different base combinations, and with or without cavity varnish.
      This resulted in 20 different restoration combinations. The other four teeth
      remained unrestored. Aging for 3 months and 1 year in 1% NaC1 at 20 degrees C
      followed. After aging, 80 of the restored teeth and the four unrestored teeth
      were subjected to an in vitro bacterial challenge for 36 days. The other 40
      specimens were placed in an acidified (pH 4.0) broth for the same length of time.
      Sections were prepared for polarized light microscopy, and outer wall and dentin
      carious lesions were measured. The results were evaluated with one-way ANOVA and
      Tukey's Student range test with a critical level of statistical significance of p
      < 0.05 and p < 0.005. Lesions produced by bacterial challenge were significantly
      smaller than those formed by acidified broth. Aging time and varnish did not
      significantly influence lesion size. Low copper amalgam, a calcium hydroxide
      paste base, and restoration per se significantly reduced lesion size.
      Reproducible measurement of wall lesion length was not possible. Secondary caries
      lesion size can be minimized by judicious selection of restoration material
      combinations.

PMID- 7722938
TI  - Influence of cryolite on the properties of polycarboxylate cement.
AB  - Zinc oxide, the inorganic component of polycarboxylate cement, was mixed with the
      filler cryolite (Na3A1F6) in various proportions that ranged from 10% to 50%.
      These powder combinations were mixed with polyacrylic acid in three powder-to
      liquid ratios of 1:1, 1.5:1, and 2:1 (w/w). The physical properties of the
      resulting cements such as setting time and compressive and diametral tensile
      strengths were determined. It was observed that the setting time increased with
      an increase in cryolite content. The compressive and diametral tensile strengths
      also increased by twofold with a concentration of 20% cryolite.

PMID- 7722939
TI  - An in vivo recording of variations in oral temperature during meals: a pilot
      study.
AB  - Thermocycling is often used in the in vitro evaluation of marginal leakage of
      dental restorations. The in vivo temperatures occurring during meals were
      recorded at different surfaces of restored teeth, to compare the variations in
      temperature with laboratory thermocycling. Temperatures were recorded with
      thermocouples at three different sites: (1) on the facial surface of a silver
      amalgam restoration, (2) at the base of a silver amalgam restoration and (3)
      within the root canal. The maximal temperature differences between upper and
      lower extremes were 29.6 degrees C at the base of a coronal restoration, 27.1
      degrees C at the facial surface, and 11.8 degrees C within the root canal. A
      practical regimen for these experiments is suggested in the light of these ranges
      because many thermocycling regimens in in vitro studies appear extreme or
      unrealistic.

PMID- 7722940
TI  - The effect of dental prophylaxis instruments on the surface roughness of metals
      used for metal ceramic crowns.
AB  - Prophylactic instruments may cause surface deterioration of metal crown margins,
      which could cause or aid the retention and accumulation of plaque. In this
      investigation, highly polished metal disks of high content gold (RX Y), low
      content gold (Aspen), silver palladium (RX 91), and nickel-chrome alloy (REX III)
      had their surfaces tracked with an explorer, hand scaler, curette, and a Dentsply
      Cavitron instrument. The surface roughness was measured with a profilometer. The
      results indicate that the high content gold was the least resistant to surface
      deterioration and the ultrasonic scaler caused the most surface deterioration to
      all the metals.

PMID- 7722941
TI  - Technique to improve surveying in confined areas.
AB  - Current surveying instrumentation precludes the thorough analysis of some areas
      of cast topography. The use of readily available, supplemental instrumentation
      when casts are surveyed will enhance removable partial denture therapy. In
      particular, facial embrasures and rest seats can be advantageously studied with
      this modified technique.

PMID- 7722942
TI  - A simplified method for removing excess cement after final cementation of fixed
      partial dentures.

PMID- 7722943
TI  - What floor nurses want to hear from you.
AB  - This article explores how a thorough, concise, and organized transfer report can
      help the PACU nurse effectively communicate the patient's condition, help the
      floor nurse anticipate the patient's needs, and facilitate the patient's recovery
      period. A three-step process is recommended for developing a systematic approach
      to the transfer report.

PMID- 7722944
TI  - The care of patients with Parkinson's disease.
AB  - Possible etiologies, pathophysiologies, manifestations, and the medical
      management of Parkinson's disease (PD) are discussed. Nursing interventions for
      the perioperative period and special considerations for postsurgical patients
      with PD are presented.

PMID- 7722945
TI  - Reading research critically: assessing the validity and reliability of research
      instrumentation--Part 2.
AB  - Accurate measurement of research variables is necessary so that research
      consumers can trust that it is the research intervention that affected the change
      in the outcome variable, not some extraneous error component. Reliability is the
      accuracy with which the research instruments measure the variable that they are
      designed to measure. A number of known threats to instrument reliability should
      be anticipated by the researcher and looked for the consumer. These threats are
      presented in this article.

PMID- 7722946
TI  - Teams: one kind doesn't fit all.
AB  - The use of teams to implement change and to deal with problems is being presented
      as the most effective and efficient way to manage in the "new" organization.
      Although there are data to support the concept that self-managed teams are
      effective, it is important to note that not all teams can or should be structured
      with that expectation. Choosing the right kind of team for the job at hand is
      equally as important as the use of a team approach.

PMID- 7722947
TI  - A PACU classic. Interview by Anne Allen.
AB  - A classic can be defined as a model, an outstanding representative of lasting
      significance and recognized value. Jovita Keane Gilligan, RN, fits the
      description. This energetic, enthusiastic, and stylish woman by all measures is a
      model, for she certainly has been an outstanding representative of her
      profession. Her work in organizing postanesthesia nurses and supporting their
      continuing education has been significant and of lasting value. This article
      offers a glimpse of a model worthy of emulation, a classic.

PMID- 7722948
TI  - Notes from the American Society of Anesthesiologists annual meeting.

PMID- 7722949
TI  - Seek first to understand.

PMID- 7722950
TI  - From "my patient" to "our patient".

PMID- 7722951
TI  - Forced-air warming versus routine thermal care and core temperature measurement
      sites.
AB  - Hypothermia occurs commonly during the perioperative period and is preventable
      with proper warming measures and body temperature monitoring. Using a
      prospective, randomized study design, we compared forced-air warming (Warm Touch,
      Mallinckrodt Medical, Inc, St Louis, MO) (n = 15) with routine thermal care (n =
      14) during the intraoperative and early postoperative periods. The results show
      that compared with routine thermal care, forced-air warming resulted in higher
      core temperatures both intraoperatively and postoperatively. The incidence of
      shivering was lower and thermal comfort scores were higher in the warming group.
      A secondary focus in this study was to assess the correlation between body
      temperatures measured at the urinary bladder, oral cavity, rectum, and tympanic
      membrane. The results indicated that the sites most highly correlated with
      tympanic temperature (listed in order of most to least correlated) were the
      bladder, rectum, and oral cavity. Assuming tympanic temperature is most
      representative of "core" temperature, oral measurements were likely to
      underestimate core temperature, whereas bladder and rectal temperatures
      overestimated core temperature. The relationship between body temperatures
      measured at commonly used monitoring sites must be recognized by nurses to
      account for the tendency to overestimate or underestimate core temperature. This
      knowledge can be applied in the management of patients in the operating room or
      PACU and specifically in the evaluation of PACU patients before discharge.

PMID- 7722952
TI  - Can advance directives assure that patients' decisions will be considered?
AB  - When the Patient Self-Determination Act of 1990 was enacted, health care
      facilities were mandated to question all patients regarding their choices in
      health care matters. Since that time, advance directives have received mixed
      reviews from health care providers, patients, and families. Much of the
      controversy results because advance directives vary from state to state, are
      poorly understood by health care providers and patients, and the laws are stated
      in vaguely defined terms. Understanding the laws at the state and local level can
      help educate professionals, who can share this information with other staff
      members, family, and patients.

PMID- 7722953
TI  - Death in the operating room and postanesthesia care unit: helping nurses to cope.
AB  - The death of patients in the OR and PACU is an unexpected event that can cause
      grief, burnout, and turnover among the caregivers who work there. In this era of
      emphasis on quality, customer satisfaction, and cost containment, prevention of
      these negative outcomes is important. Although there is scant literature devoted
      to how nurses cope with patient death in this setting, many of the principles
      described in the literature for other settings can be applied to assist
      caregivers to view death as a growth-producing experience, both personally and
      professionally.

PMID- 7722954
TI  - Operation Fascination.
AB  - Operation Fascination is an educational program about the perioperative
      experience targeted at the school-age community. The goals are to help children
      gain a better understanding of the perioperative process by incorporating it in
      the school curriculum and extracommunity curricula and to make the perioperative
      nurse more aware of school-age children's misconceptions. A literature search
      showed that little has been written about perioperative education of school-age
      children outside the health care institution. Therefore, this article shares the
      development and initiation of Operation Fascination as well as describes the
      importance and benefits of offering this type of program to the community.

PMID- 7722955
TI  - A case study: identification and treatment of narcotic depression in the
      ambulatory surgical patient.
AB  - The staff in a freestanding ambulatory surgical center (ASC) must be prepared to
      identify and treat all emergencies and untoward patient responses. This case
      study exemplifies some of the problems encountered with a patient who had surgery
      late in the day and who did not have local anesthetic infiltrated for pain
      control after inguinal herniorrhaphy. In a retrospective analysis and discussion
      of the case, the caregivers identified that, in addition to the narcotics given,
      this patient's lengthy postoperative course was further complicated by inadequate
      intravenous fluid replacement and ambulation too soon after narcotic
      administration. From this case study a number of lessons were identified,
      particularly for the freestanding ASC. These lessons relate to adequate staffing
      (two nurses) for late cases, the importance of the presence of the
      anesthesiologist at the center until all patients have been discharged, the need
      to assure that home conditions are adequate for patients discharged late in the
      day, and the staff's ability to quickly and accurately identify and treat
      untoward patient responses.

PMID- 7722956
TI  - Circadian rhythms of corneal mitotic rate, retinal melatonin and immunoreactive
      visual pigments, and the effects of melatonin on the rhythms in the Japanese
      quail.
AB  - We investigated circadian ocular rhythms in the Japanese quail, Coturnix coturnix
      japonica. The birds were placed under light-dark cycles (LD 12:12), constant
      light (LL) and constant darkness (DD), and the retinas were dissected out at four
      hour intervals throughout 24 h. Following measurements were performed. (1)
      Melatonin content in the retina was measured by radioimmunoassay. It was low in
      light and several folds higher in darkness under LD 12:12. The rhythm continued
      in DD, but disappeared in LL. (2) Mitotic figures in the corneal epithelium were
      counted. Similar rhythms to the melatonin content were observed in the corneal
      mitotic rate with a slight phase delay. (3) The retinas were fixed at 4-h
      intervals and immunostained with anti-bovine rhodopsin serum and anti-chicken
      iodopsin monoclonal antibodies. The outer segments of photoreceptor cells were
      stained intensively throughout 24 h in LD 12:12, LL and DD. In contrast, the
      stainability of the locus close to the outer limiting membrane where the Golgi
      apparatus exists changed diurnally. Scores showing the ratio of cells with
      positive staining indicated high values from 4 h after the onset of light to the
      beginning of dark phase under LD 12:12. The values were high throughout 24 h in
      LL and intermediate or low in DD. (4) To investigate the effect of melatonin on
      the corneal mitotic rate and visual pigments at the Golgi region, melatonin was
      injected into one eye and saline into the contralateral eye. Melatonin induced a
      phase advance in the corneal mitotic rate under LD 12:12, but did not induce a
      rhythm under LL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722957
TI  - Regulation of sex-specific feeding behavior in fiddler crabs: physiological
      properties of chemoreceptor neurons in claws and legs of males and females.
AB  - This study examined properties of chemoreceptor neurons in the claws and legs of
      the fiddler crabs Uca pugilator and U. pugnax. The primary goal was to establish
      the neural basis of previously observed greater female sensitivity to feeding
      stimulants, and secondarily to compare physiological properties of chemoreceptor
      neurons in these semi-terrestrial crustaceans with those of fully aquatic forms.
      Sensitivity of chemoreceptor neurons in claws and legs is sex-specific;
      individual neurons of females respond to lower stimulus concentrations than male
      chemoreceptor neurons, and equivalent concentrations elicit greater spiking in
      female vs male chemoreceptor neurons. Thus, the population of chemoreceptor
      neurons in females expresses lower thresholds and greater average sensitivity
      than in males. Greater sensitivity of claw neurons explains observations
      indicating that females continue to feed at food levels too low to stimulate
      males. Sensitivity differences in leg neurons of males vs females have no clear
      behavioral correlate, but suggest that females can orient to more dilute stimuli
      than males. Chemoreceptor neurons of fiddler crabs have low sensitivities and
      slow rates of adaptation compared to other crustaceans. Also, neurons in claws
      adapt less slowly than neurons in legs, which may reflect subtle differences in
      the chemical stimulus environment experienced by claws vs legs.

PMID- 7722958
TI  - Inhibition of taurine and 5'AMP olfactory receptor sites of the spiny lobster
      Panulirus argus by odorant compounds and mixtures.
AB  - 1. The effects of the odorant compounds adenosine-5'-monophosphate (5'AMP),
      ammonium, betaine, L-cysteine, L-glutamate, DL-succinate, and taurine and of
      mixtures of these compounds on binding of taurine and 5'AMP to dendritic membrane
      from the olfactory organ of spiny lobsters (Panulirus argus) were quantified to
      evaluate the contribution of inhibition of odorant-receptor binding to the
      generation of physiological responses to mixtures. 2. Taurine binding sites
      belong to two affinity classes, while 5'AMP binding sites belong to a single
      affinity class. Binding of either taurine or 5'AMP was partially inhibited in an
      apparently noncompetitive, concentration dependent fashion by most odorant
      compounds, with 25-40% inhibition by 1 mM of odorant. Mixtures of two or more
      odorant compounds also inhibited binding of taurine or 5'AMP to its sites.
      However, the inhibition by mixtures was often significantly less than expected
      from the inhibition produced by a mixture's components assuming either a
      noncompetitive or competitive mechanism. 3. By including this binding inhibition
      between compounds into models for predicting physiological responses to mixtures
      from the responses to the components, the predictive power of the models is
      significantly improved. This result strongly suggests that binding inhibition can
      influence the physiological responsiveness of chemoreceptor cells to mixtures.

PMID- 7722959
TI  - Body image and dieting in pregnancy.
AB  - The present study evaluated body image, body satisfaction and dieting practices
      in pregnancy: a stage of life when social pressures for slimness might be
      expected to be relaxed. Pregnant women had lower scores on the Drive for Thinness
      subscale of the Eating Disorder Inventory, and when Body Mass Index was
      controlled for, had significantly lower Body Dissatisfaction Scale scores than
      non-pregnant women. They also rated themselves as less overweight in terms of
      body size. Dietary restraint was lower and current attempts to lose weight were
      less frequent in the pregnant group. However, there was no evidence that
      pregnancy was associated with any relaxation of body image ideals: pregnant women
      chose a similar size of figure to non-pregnant women as their ideal. These
      results suggest that the state of pregnancy can be associated with reduced weight
      concern despite an increased body size, but the effect appears to be state
      dependent and is not mediated by shifts in body size ideals.

PMID- 7722960
TI  - The experience of food craving: a prospective investigation in healthy women.
AB  - This study aimed to provide a detailed analysis of the experience of food craving
      in a healthy, non-clinical group of women. Twenty-five women who reported food
      cravings prospectively recorded their experiences over a period of 5 weeks using
      a Food Craving Record. The average number of cravings recorded was just under 2
      per week. Craving for chocolate amounted to 49% of all the food cravings. Subtle
      differences in the change in arousal and hunger were noted between chocolate
      cravings and those for other sweet foods. Additional differences were found
      between these cravings and those for savoury foods, in their situational
      circumstances and speed of disappearance. There was a premenstrual increase in
      food cravings but no selective change in the types of food craved. Overall, the
      food cravings reported by these women were hunger-reducing, mood-improving
      experiences, directed at wanting to consume highly pleasant tasting food. This
      analysis should serve as a template against which other subject groups and other
      forms of craving may be explored.

PMID- 7722961
TI  - Gestational diabetes: a case-control study of women's experience of pregnancy,
      health and the child.
AB  - Women with previous gestational diabetes (n = 113) and controls (n = 226) were
      studied retrospectively by means of questionnaires. Women with gestational
      diabetes reported less well-being (p < 0.05), psychic health (p < 0.001) and
      vigour (p < 0.001) during pregnancy and a less positive experience of pregnancy
      (p < 0.001) than controls. They also recalled more worry about health during
      pregnancy than controls (p < 0.001), reported more physical health problems (p <
      0.05), more worry about health (p < 0.05) and kept to a diet more often after
      pregnancy (women with gestational diabetes 34%, controls 13%, p < 0.001).
      Although most of the women in the groups were not troubled, it was clear that the
      gestational diabetes influenced their experience of health negatively but
      motivated them to adopt a healthy lifestyle. Initial treatment with insulin
      seemed to be slightly more stressful than diet only.

PMID- 7722962
TI  - The evaluation of life event data.
AB  - Data from three life event studies are compared. The interviews covered events
      that occurred within a period of 2 years before interview. The same inventory was
      used in each of the studies. Samples were drawn from depressives, myocardial
      infarction patients and an industrial worker population. The patient groups were
      interviewed twice within 4 weeks. Fewer than 50% of the total number of events
      reported in the retests were recorded twice. For events reported in both
      interviews the correlations of subjective appraisals were only moderate. There is
      considerable fall-off for reports of events occurring more than 6 months before
      interview. It was expected that the severest events would have the lowest, and
      the least severe ones the highest frequencies. Instead, inappropriate labels of
      the rating scales led to clusterings of severity ratings at their extreme points.
      Numbers of events and severity ratings were positively correlated with measures
      of depression.

PMID- 7722963
TI  - Life events and the onset of rheumatoid arthritis.
AB  - This study used the Life Events and Difficulties Schedule to assess whether an
      excess of life events occurred prior to onset of rheumatoid arthritis (RA) in 60
      consecutive out-patients. There was no evidence of an excess of events of any
      kind during the 12 months before onset of RA. There was no difference between
      seropositive and seronegative RA or between those with and without a family
      history. There was a non-significant trend for an excess of events before onset
      compared with after; this may be explained by the reduction of events after onset
      as a consequence of disabling disease. The prevalence of psychiatric disorder
      measured using the Psychiatric Assessment Schedule was 13.3% at the time of
      interview.

PMID- 7722964
TI  - Psychological distress and disability in back pain patients: evidence of sex
      differences.
AB  - Using a psychological screening questionnaire, the incidence of psychological
      distress in back pain patients attending a chiropractic out-patient clinic was
      sought. In contrast to other back pain populations, only a small proportion of
      the sample (7.2%) showed overt signs of psychological distress. However, a
      relatively large proportion of these patients (45%) were classified as at risk of
      developing significant psychological distress. Sex, age and clinical history
      appeared to have very little effect on the psychological classification of
      patients, although women scored significantly higher overall on the psychological
      questionnaires. The relationship between distress and patients' self-reported
      disability was also investigated and shown to be particularly sensitive to sex
      effects. Hence, psychological distress accounted for 1 and 32% of the total
      variance in disability scores in male and female patients, respectively.

PMID- 7722965
TI  - Self-esteem and behavioural adjustment in children with epilepsy and children
      with diabetes.
AB  - This paper describes a study to investigate the relationship between self-esteem
      and behavioural adjustment in two groups of children with chronic illness, one
      with epilepsy and the other diabetes. A total of 62 children with epilepsy and 91
      children with diabetes were recruited from the total population of children aged
      8-15 attending the epilepsy and diabetic clinics at a children's hospital over a
      12 month period. Self-esteem and behavioural adjustment were assessed with the
      Harter and Achenbach Questionnaires respectively. The results showed the children
      with epilepsy were consistently more behaviourally disturbed and had lower self
      esteem than children with diabetes. The independent completion of the
      questionnaires, (the Harter by the child and the Achenbach by the parents)
      increases the validity of the findings. Long duration of illness was the most
      consistent illness variable associated with poor behavioural adjustment in the
      two groups. The cross-sectional design of the study did not make it possible to
      draw any definite conclusions about the causal or temporal relationship between
      low self-esteem and behavioural disturbance. Once again, the potential value of
      prospective studies into the psychosocial adjustment of children with chronic
      illness is highlighted.

PMID- 7722966
TI  - Transient loss of serum protective activity following short-term stress: a
      possible biochemical link between stress and atherosclerosis.
AB  - Very low density lipoproteins (VLDL) are toxic to aortic endothelial cells in
      vitro, and toxicity preventing activity (TxPA) inhibits this toxic effect of
      VLDL. Stress, an established arteriosclerosis risk factor, was examined for its
      effect on TxPA and on the ability of serum to protect endothelial cells from in
      vitro injury by VLDL. A standardized mirror tracing task with noise was
      administered to four healthy subjects. Blood samples were obtained at 0, 30,
      (stressor) 35, 50 and 80 min. Cortisol and non-esterified fatty acids increased
      during the stress period. TxPA significantly decreased following the stressor and
      had recovered by 80 min. When the ratio of non-TxPA/TxPA rose above 2, serum was
      no longer able to protect the cells from VLDL injury. If endothelial cells in
      vivo respond similarly to the endothelial cells in culture, the effect of stress
      on atherosclerosis may be mediated through these transient decreases in TxPA.

PMID- 7722967
TI  - Behavioral and psychophysiological predictors of self-monitored 19 month blood
      pressure change in normotensives.
AB  - Selected demographic, behavioral and psychophysiological variables (sex of the
      subject, exercise, coffee and cigarette consumption, baroreceptor stimulation
      dependent pain dampening, initial blood pressure, body mass index, daily stress
      rating, reactivity to mental stress as measured by change in stress rating and
      heart rate and blood pressure from resting to mental arithmetic conditions) were
      entered into a stepwise multiple-regression equation to predict changes of
      oscillometrically self-measured tonic blood pressure in 80 normotensives over a
      19 month period. The prediction equation (r = 0.55) associated increases in
      diastolic blood pressure with baseline diastolic blood pressure, more
      baroreceptor stimulation-dependent pain inhibition, and less heart rate change
      during mental arithmetic. There were no significant predictors of systolic
      changes, and no sex differences. Results are discussed in terms of the learned
      model of hypertension.

PMID- 7722968
TI  - Endometrial biopsy dating. Interobserver variation and its impact on clinical
      practice.
AB  - To determine the degree of interobserver variation and the level of correlation
      in endometrial biopsy (EB) interpretation, five pathologists interpreted 30 EBs
      randomly selected from all EBs performed according to standard criteria. An EB
      was considered out of phase (OOP) if there was greater than a two-day lag in
      histologic development relative to the onset of the next menstrual period.
      Interobserver variation among the five pathologists was 0.85 and 0.82 days for
      one- and two-day dating ranges, respectively. Coefficients of correlation for
      histologic interpretation ranged from 0.839 to 0.934 (P < .0001). Seventy percent
      to 74% of the time all five pathologists agreed that a given EB was in phase or
      OOP. The low interobserver variation and high correlation between observers
      further validates the EB as a diagnostic test. However, up to 30% of the time a
      clinical management decision may be altered depending upon who interprets the EB.
      Thus, even with low interobserver variation, the clinical consequence of small
      changes in EB interpretation may be significant.

PMID- 7722969
TI  - The severely abused woman in obstetric and gynecologic care. Guidelines for
      recognition and management.
AB  - Of women who consult an obstetrician-gynecologist, 1.5-20% have or are
      experiencing severe physical, emotional and/or sexual abuse. These women present
      in characteristic ways that alter the provider-patient interaction. This paper
      describes techniques for taking a history, conducting a physical examination,
      planning therapy and counseling for gynecologic surgery.

PMID- 7722970
TI  - Infertile couples with a normal hysterosalpingogram. Reproductive outcome and its
      relationship to clinical and laparoscopic findings.
AB  - The purpose of this study was to retrospectively investigate the clinical course
      of infertile couples following a normal hysterosalpingogram (HSG) to determine
      the reproductive outcome and assess the diagnostic value of subsequent
      laparoscopy (LSC). The infertile couples (N = 132) were aged 29 +/- 0.5 SD years,
      with 3.2 +/- 0.4 years of infertility, and were followed for an average of 17 +/-
      1.5 months after the HSG. Twenty-nine percent of patients became pregnant after a
      normal HSG performed with water-soluble contrast medium. There was a fourfold
      greater rate of pregnancy during the first three months after a normal HSG than
      during any other three-month interval up to one year. Thirty-four of the initial
      132 patients required laparoscopy because of failure to conceive or suspected
      pelvic disease based on symptoms or the results of a pelvic examination. Among
      the 34 patients receiving LSC, pelvic pathology was found in 19 (56%). Corrective
      surgery and/or a change in therapy occurred in 60% of cases after LSC. There was
      an increased proportion of abnormal findings with increasing time intervals
      between HSG and LSC but not with increasing intervals of infertility before HSG.
      Abnormal uterine bleeding was predictive of abnormalities at LSC, while prior use
      of oral contraceptives correlated negatively with pelvic pathology. In women in
      infertile couples who have a normal HSG: (1) LSC should not be performed before
      three months after a normal HSG because of the potential therapeutic effect of
      HSG, (2) LSC should be performed after a normal HSG if pregnancy has not occurred
      by at least one year because of the high incidence of pelvic pathology, and (3)
      HSG using water-soluble contrast media has a therapeutic effect comparable to
      that described for oil-soluble contrast media.

PMID- 7722971
TI  - Fetal myelomeningocele. Is antenatal ultrasound useful in predicting neonatal
      outcome?
AB  - The objective of this study was to determine if an ultra-sound examination, when
      performed in the third trimester immediately preceding delivery, is useful in
      predicting outcome in infants with a myelomeningocele. A retrospective review was
      undertaken of prenatal ultrasound records and pediatric outcome data on fetuses
      with isolated myelomeningocele referred to our institution after 28 weeks'
      gestation during a three-year period. Macrocephaly proved to be the one antenatal
      ultrasound finding that most correlated with later poor outcomes in infants with
      myelomeningocele. Macrocephalic fetuses had a longer mean hospital stay after
      birth and were more likely to have significant respiratory and feeding
      difficulties. No fetus with macrocephaly had a normal mental score, and all had
      severe motor deficits on later follow-up testing. The ultrasound diagnosis of
      macrocephaly identified a group of fetuses with myelomeningocele, who were at
      highest risk of neonatal problems and developmental delay. Cesarean delivery and
      aggressive medical treatment of complications did not improve the outcome in
      these infants. This finding will be useful when counseling patients regarding
      route of delivery and in pediatric decisions regarding treatment of
      complications.

PMID- 7722972
TI  - Clinical and subclinical condyloma. Rates among male sexual partners of women
      with genital human papillomavirus infection.
AB  - Sixty-three regular male sexual partners of women with proven genital human
      papillomavirus (HPV) infection or its associated lesions were examined by
      colposcopy and biopsy (when necessary) to determine the prevalence of penile
      condyloma among them. Fifteen (24%) were found to have histologic evidence of
      condyloma. The severity of the women's lesions did not necessarily reflect that
      of lesions found in their sexual partners. The majority (54%) of the HPV
      associated lesions were located on the penile body, followed by the penile root
      (25%). We found no cases of premalignant or malignant penile lesions. After
      controlling for the confounding factors of socioeconomic status and lesion
      location and comparing the data to those compiled from the English-language
      literature, we arrived at various theories about the very low rate of infection
      in our population. One possibility is the protective effect of circumcision,
      partly because the preputium is a major site of bacterial and viral colonization.
      The possibility of different strains of HPV in the Jewish Israeli population and
      certain socioeconomic factors that may limit the spread of sexually transmitted
      diseases may be the basis for future study.

PMID- 7722973
TI  - Preventing severe ovarian hyperstimulation syndrome in an in vitro
      fertilization/embryo transfer program. Use of follicular aspiration after human
      chorionic gonadotropin administration.
AB  - In 3,972 human menopausal gonadotropin (hMG) and human chorionic gonadotropin
      (hCG)-stimulated menstrual cycles, severe ovarian hyperstimulation syndrome
      (SOHSS) developed in 10 patients (0.25%), while in 627 hMG-, hCG- and
      gonadotropin releasing hormone analog (GnRH-a)-stimulated cycles, 6 patients
      (0.95%) developed SOHSS. In cases of threatening SOHSS in the follicular phase
      (excessive estradiol values, multiple follicles), a preventive method was
      applied: follicular aspiration 12 hours after hCG administration and regular
      oocyte retrieval 36 hours after hCG (17 patients). The method of post-hCG
      aspiration in one ovary was effective, leading to the withdrawal of all signs of
      SOHSS within six days after the second aspiration. In hMG-stimulated, pretreated
      patients there were four deliveries of seven healthy infants (two singleton, one
      twin and one triplet), while one pregnancy in seven GnRH-a-stimulated and
      pretreated patients ended in a spontaneous abortion. Post-hCG aspiration is a
      quick, simple and effective method that prevents the development of SOHSS and
      permits pregnancy in the treated cycle. Although the pregnancy rate in patients
      who developed SOHSS was higher (100% per embryo transfer), one should also
      consider the high spontaneous abortion rate (33.3% for the hMG- and 50% for the
      GnRH-a/hMG-treated groups) and the fact that SOHSS is a life-threatening
      condition, demanding expensive, intensive care. According to our experience, post
      hCG follicular aspiration is the treatment of choice in patients with signs of
      SOHSS.

PMID- 7722974
TI  - Reduction in the rate of cesarean birth with active management of labor and
      intermediate-dose oxytocin.
AB  - Active management of labor (AML) was introduced to lower the cesarean birth rate
      in nulliparas by using oxytocin at a dose higher than commonly used in this
      country but less than that used in other AML studies. Cesarean birth rates among
      nulliparas were compared before and after introduction of AML. When indicated,
      oxytocin was begun at 2 mIU/min rather than 6 mIU/min, as used in other, similar
      studies. Three-hundred fifty-two historical control and 160 AML study patients in
      labor were compared. Analysis utilized chi 2 and Student's t test. AML patients
      had a lower rate of cesarean birth, 6.3%, than did control patients in
      spontaneous labor, 13.1% (P = .03). The overall cesarean birth rate for all
      nulliparas (including inductions and cesarean sections prior to labor) fell from
      23% to 16% (P = .04). The introduction of an AML program using intermediate-dose
      oxytocin into the clinic service at a large, private teaching hospital has safely
      reduced the rate of cesarean births among nulliparas.

PMID- 7722975
TI  - The cotton swab test. Receiver-operating characteristic curves.
AB  - The purpose of this prospective, cohort study was to perform a receiver-operating
      characteristic (ROC) analysis of the cotton swab test and its ability to predict
      stress incontinence. The study was performed in a tertiary care gynecologic
      urology clinic over a period of 3.5 years. Two hundred sixty-three women
      presenting with the complaint of urinary incontinence formed the basis of the
      cohort. Subjects were classified as having genuine stress urinary incontinence or
      incontinence secondary to another factor following urodynamic testing. The cotton
      swab test was performed as part of the standard urogynecologic assessment.
      Measurement was made of the resting, straining and calculated resultant change in
      angle. ROC curves were calculated for each of the angles measured. The resultant
      ROC curves demonstrated that straining angle has the best discriminatory power in
      the diagnosis of genuine stress urinary incontinence. The optimum cut-off point
      for this discrimination is a deflection of 40 degrees from the horizontal, with a
      resultant sensitivity of 83%. Despite the diagnostic trend, the sensitivity of
      the straining angle does not allow one to confidently make a diagnosis of genuine
      stress urinary incontinence without a confirmatory evaluation. The test, however,
      can be beneficial in the counseling and triage of women with lower urinary tract
      complaints.

PMID- 7722976
TI  - Hemoglobin levels during twin vs. singleton pregnancies. Parity makes the
      difference.
AB  - A retrospective, case-control study of 200 consecutive twin and singleton
      gestations matched for parity was conducted to challenge the hypothesis that
      lower hemoglobin values appear more often during twin gestations. The database
      consisted of hemoglobin levels recorded during each trimester. Comparisons were
      made between the mean hemoglobin levels and incidence of values > 11, 9-11 and <
      9 g/dL. Significantly lower mean (+/- SD) hemoglobin values were observed during
      the first (11.94 +/- 1.1 vs. 12.17 +/- 1.0, P = .026) and second (11.1 +/- 1.0
      vs. 11.48 +/- 0.9, P = .00001) trimesters in twin vs. singleton pregnancies,
      respectively. The differences resulted from lower values in multiparas with twins
      as compared with their singleton-pregnancy controls (11.8 +/- 1.2 vs. 12.2 +/-
      0.9, P = .015, for the first trimester and 11.0 +/- 1.0 vs. 11.5 +/- 0.9, P =
      .0001, for the second trimester). During the second trimester, the lower
      incidence of values > 11 g/dL (P = .005, odds ratio = .475, 95% confidence
      interval = .31-.73) and higher incidence of values between 9 and 11 g/dL (P =
      .0008, odds ratio = 2.06, 95% confidence interval = 1.34-3.19) may account for
      the significant differences in mean values. There were no differences between
      third-trimester values, between nulliparas in both groups or between nulliparas
      and multiparas in each group. We conclude that the lower hemoglobin levels in
      twin gestations were associated with multiparity and were statistically
      significant during the first and second trimesters. This subgroup of twin
      pregnancies may benefit from further research and possibly from closer
      hematologic care and monitored iron supplementation.

PMID- 7722977
TI  - Anastomosis of the freshly divided uterine horns of rats with the CO2 laser vs.
      microsurgery.
AB  - We used the CO2 laser (group 1) and conventional microsurgery (group 2) for
      anastomosis of the freshly divided uterine horns of rats and compared the two
      methods. Each group was then compared with a control group in whom only
      exploration was carried out at laparotomy. Comparison was done regarding the
      clinical and histologic results. In addition, serum levels and tissue
      concentrations of alkaline phosphatase (ALP) and lactic dehydrogenase (LDH) were
      measured, and the three groups were compared. No significant difference was found
      between the mean adhesion scores of groups 1 and 2; however, when the control
      group was compared with the other groups, the differences were statistically
      significant. The tubal patency rates in groups 1 and 2 and the control group were
      83.3%, 79.2% and 100%, respectively, and the pregnancy rates in those groups were
      54.5% (6/11), 45.5% (5/11) and 100% (10/10). The differences in tubal patency and
      pregnancy rates between groups 1 and 2 were not significant, but when each was
      compared with the control group, the differences were significant. The mean
      scores for mucosal regeneration and disruption of the muscularis layer in group 1
      were significantly lower than those in group 2. Serum levels and tissue
      concentrations of ALP and LDH in the control group were lower than in groups 1
      and 2, and the differences between the control group and each of the other groups
      were significant; however, no significant difference was found between groups 1
      and 2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7722978
TI  - Double-balloon instillation device for second-trimester abortion. Outcome in 340
      consecutive cases.
AB  - For the past five years we have used a double-balloon device for extraovular
      instillation of prostaglandin solution for termination of midtrimester pregnancy.
      In 340 consecutive cases a success rate of 91% (abortions within 24 hours) was
      achieved, with a mean instillation-to-abortion interval of 17.5 +/- 6.5 (SD)
      hours in nulliparas versus 12.8 +/- 6.1 in multiparas (P < .005). The
      instillation of continuous, low-dose prostaglandin solution into the extraovular
      space resulted in very few side effects and no complications. Furthermore, the
      technique was used successfully in women who had undergone one or more cesarean
      sections in the past. The use of prostaglandin E2 (PGE2) resulted in shorter
      instillation-to-abortion intervals than did prostaglandin F2 alpha (P < .01); 500
      micrograms/h of PGE2 solution was needed in nulliparas, whereas 250 sufficed in
      multiparas.

PMID- 7722979
TI  - Spontaneously acquired, unilateral absence of the adnexa. A case report.
AB  - A free-floating, calcified cyst was found in the peritoneal cavity in association
      with unilateral absence of the adnexa. The evidence was that it was due to
      torsion and separation of the adnexa from their supporting structures. This
      phenomenon may be a cause of congenital absence of the ovary.

PMID- 7722980
TI  - Doppler velocimetry and fetal heart rate pattern observations in acute cocaine
      intoxication. A case report.
AB  - While the use of cocaine in pregnancy continues to be a significant contributor
      to adverse maternal and perinatal outcomes, systematic study of the physiologic
      effects of cocaine in human gestation remains difficult. In a case of acute
      cocaine intoxication in the third trimester, Doppler velocimetry suggested a
      physiologic response from the uterine artery but not the umbilical artery.
      Furthermore, the abnormal uterine artery velocimetry was associated with a
      positive nonreactive contraction stress test, which became negative and reactive
      as the effects of the cocaine wore off and the velocimetry returned to normal.
      These observations suggest that the uterine arteries are more sensitive to
      cocaine than are the umbilical arteries and that abnormal fetal heart rate
      patterns during acute cocaine intoxication may be transitory.

PMID- 7722981
TI  - Constriction of the umbilical cord by an amniotic band, with fetal compromise
      illustrated by reverse diastolic flow in the umbilical artery. A case report.
AB  - Constriction of the umbilical cord by an amniotic band is a rare entity,
      associated with a high rate of fetal mortality and congenital anomalies. A case
      occurred with early detection and successful intervention for fetal compromise
      caused by the amniotic band, which was associated with first-trimester
      amniocentesis. This is the first known report of ultrasound Doppler flow studies
      in a case of umbilical cord constriction by an amniotic band, showing reverse
      diastolic flow in the umbilical arteries.

PMID- 7722982
TI  - Laser lithotripsy in pregnancy. A case report.
AB  - Laser lithotripsy is a new method of treating symptomatic urolithiasis. The
      pulsed dye laser lithotripter uses coumarin to deliver energy with a visible peak
      wave-length of 504 nm. This energy is transmitted to the calculus through an
      optical fiber, and mechanical disruption of the stone occurs when multiple pulses
      of laser energy are applied to the surface of the stone. The method is safe and
      effective for impacted ureteral calculi. A woman at 20 weeks of pregnancy
      experienced intractable pain secondary to a 9-mm, distal ureteral stone. She was
      treated successfully with endoscopic fragmentation using pulsed dye laser
      lithotripsy.

PMID- 7722983
TI  - Pregnancy and functional deterioration in a woman with a univentricular heart. A
      case report.
AB  - A patient who had undergone Pott's procedure and a right Blalock-Taussig shunt in
      childhood for complex cyanotic congenital heart disease with a single ventricle
      presented with a planned pregnancy at age 22. Although asymptomatic prior to
      pregnancy, she experienced functional deterioration from the first trimester and
      had preterm labor with a footling breech presentation at 29 weeks following
      prelabor rupture of the membranes. A normal, 900-g female infant was delivered by
      cesarean section. Despite delivery the patient continued to experience
      progressive functional deterioration and returned to her prepregnancy cardiac
      status only after a Fontan operation, performed 14 months postpartum.

PMID- 7722984
TI  - Fetal faciocervical teratoma with anemia and thrombocytopenia. A case report.
AB  - A massive teratoma in the faciocervical region was found in a fetus at 21 weeks,
      with laboratory evidence of anemia and thrombocytopenia. Vaginal delivery was
      achieved by cardiocentesis followed by Laminaria tent insertion, dilation and
      evacuation.

PMID- 7722985
TI  - Umbilical cord length and acid-base balance at delivery.
AB  - An abnormally short or long umbilical cord is associated with a greater risk of
      cord compression, variable fetal heart rate decelerations and fetal demise. The
      purpose of the present investigation was to determine whether any relation exists
      between an abnormal length of the umbilical cord and acid-base imbalance at
      delivery. Cord lengths were measured routinely in 3,019 consecutive pregnancies
      undergoing labor beyond 34 weeks. Short cords (13-35 cm) were found in 61 (2.0%)
      cases and long cords (80-121 cm) in 112 (3.7%) cases. Umbilical blood pH and base
      deficit values averaged the same for those pregnancies with short (7.35 +/- 0.09
      and 3.1 +/- 2.7 mEq/L, mean +/- SD), normal length (7.36 +/- 0.03 and 3.8 +/-
      1.7, mEq/L) and long (7.34 +/- 0.06 and 3.7 +/- 3.1 mEq/L) cords. A blood pH <
      7.20 was very uncommon in the presence of a short (two cases, 3.3%) or long (five
      cases, 4.5%) cord and was accompanied by an abnormal fetal heart rate pattern,
      such as severe variable decelerations or bradycardia. Finding an abnormally short
      or long umbilical cord at birth is not by itself associated with an increased
      risk of acid-base imbalance at delivery and does not require routine cord blood
      gas determination.

PMID- 7722986
TI  - Issues in the definition and measurement of drinking outcomes in alcoholism
      treatment research.
AB  - This article reviews methodological and conceptual issues regarding the choice of
      drinking outcome measures in alcoholism treatment research. The following issues
      are discussed: Should drinking outcomes be conceptualized in terms of an
      underlying unitary disorder, or should provision be made for independent outcomes
      that cover a wide variety of dimensions? Which drinking outcomes are typically
      measured in treatment evaluation studies and how are they operationalized? What
      are the empirical associations among drinking outcome measures? If multiple
      outcomes are measured, which should be given primary importance? Over what period
      of time should treatment outcome be evaluated? What procedures can be used to
      detect, correct or prevent the response bias associated with verbal report
      methods? Because outcome measures need to fit the hypotheses and practical needs
      of a particular study, it is unlikely that complete standardization can be
      achieved across all studies. Nevertheless, given the importance of drinking
      outcomes and the need for economy, two primary dependent measures are
      recommended: (1) proportion of available drinking days abstinent; and (2)
      intensity of drinking, as defined by the total amount consumed (in ounces
      absolute alcohol) during the follow-up period divided by the number of actual
      drinking days. This article also proposes a strategy that may help to guide the
      selection of outcome measures in future research.

PMID- 7722987
TI  - Measurement of drinking behavior using the Form 90 family of instruments.
AB  - Although drinking behavior is clearly a central dependent variable in alcoholism
      treatment research, the field has reached no consensus on measurement methodology
      for alcohol consumption. At least four methods for quantifying consumption have
      been commonly used in outcome studies: quantity-frequency questions, average
      consumption grids, timeline follow-back and self-monitoring. The Form 90 family
      of structured interviews was developed by collaboration among the Project MATCH
      investigators, combining the strengths of prior assessment methodologies. The
      development, structure, supporting software and training approaches for the Form
      90 instruments are described.

PMID- 7722988
TI  - Quality of life as an outcome variable in alcoholism treatment research.
AB  - Although a number of approaches to measuring alcohol consumption are available,
      these alone do not reflect the full range of changes that may be associated with
      response to treatment for alcohol abuse and dependence. What constitutes a
      sufficient index of response to alcohol treatment? At the very least, research
      should measure negative consequences of alcohol consumption, although they may be
      difficult to specify beyond the client's own perception. Associations between
      alcohol consumption and dimensions of life quality may be negative or positive in
      value and may be broadly or narrowly conceptualized, depending upon the aims of
      the study. Although models exist for the conceptualization and measurement of
      many aspects of quality of life in alcoholism and other fields, much remains to
      be specified. Still to be accomplished is a careful examination of the
      interrelationships between alcohol consumption and specific dimensions of life
      quality, particularly as these interrelationships are affected by time since
      treatment and client characteristics among other potential mediators and
      moderators. Project MATCH has attempted a broad assessment of dimensions of life
      quality beyond alcohol consumption. These variables are viewed as secondary,
      rather than primary, measures of treatment outcome. The extent to which Project
      MATCH's strategy was effective is a question that will be answered when we
      examine the interrelationships among the various dimensions of outcome and the
      differential effects of treatments on these outcome dimensions.

PMID- 7722989
TI  - Reliability enhancement and estimation in multisite clinical trials.
AB  - Clinical trials, particularly those in addictions research, often rely on self
      report data for primary dependent variables, and it is imperative to evaluate and
      to minimize both random and systematic error. This article describes methods for
      enhancing and assessing reliability of measurement in multisite clinical
      research. It begins with an overview of the two major approaches to evaluating
      the reliability of psychiatric diagnosis and verbal self-reports. A model of the
      interview process is then described, and the major sources of inconsistency that
      arise in the data collection process are identified. Based on the model, staff
      selection criteria, training techniques and quality assurance procedures are
      recommended for enhancing the reliability of interview assessments, and a
      research design appropriate for evaluating reliability in multisite clinical
      investigations is proposed.

PMID- 7722990
TI  - Issues in the selection and development of therapies in alcoholism treatment
      matching research.
AB  - There are a large number of possible approaches to the treatment of alcohol abuse
      and dependence. From a practical and methodological standpoint, however, only a
      limited number of interventions can realistically be included in research studies
      of treatment matching. A key question in planning studies of matching is what
      treatments to include. The recent book by Beutler and Clarkin on systematic
      treatment selection in general psychotherapy provides a framework within which to
      discuss alcoholism treatment matching and the criteria applied to decisions
      concerning (1) modes of treatment, (2) treatment format, (3) specific therapeutic
      strategies and the (4) treatment setting. The methodological and practical issues
      raised and the decisions reached in Project MATCH are presented in each of these
      areas. The therapies chosen for Project MATCH, based on these criteria, are
      described.

PMID- 7722991
TI  - Implementing treatment and protecting the validity of the independent variable in
      treatment matching studies.
AB  - Treatment matching research is predicated on heterogeneity among subjects and
      their differential response to treatments. The sine qua non of a treatment
      matching study is the integrity of the treatment variable, since detection of
      client-treatment interactions requires delivery of treatments that are highly
      specific, consistent and distinct. Matching research thus presents particular
      challenges in treatment implementation, as greater heterogeneity in subjects may
      generate a broader array of problems than study treatments are designed to
      address, leading to several potential threats to treatment integrity. Moreover,
      as practiced outside of research settings, treatments for alcoholism are marked
      by ideological heterogeneity and a lack of purity across approaches. In this
      article we describe the strategies used in Project MATCH to protect treatment
      integrity while treating a large and heterogeneous sample of alcoholics in a
      number of geographically distant sites. These include: strategies for treating a
      variety of alcoholics within a single treatment approach; development of clinical
      care guidelines and clinical deterioration criteria; specification of treatments
      in manuals with minimization of overlapping active ingredients; selection
      criteria for therapists intended to enhance both generalizability of findings as
      well as treatment integrity; and extensive therapist training and monitoring.

PMID- 7722992
TI  - Process assessment in treatment matching research.
AB  - A complete understanding of the effects of treatment requires an examination of
      the process by which the treatment produces the outcome as well as a thorough
      assessment of the outcomes. Process assessment assumes even greater importance in
      matching research than in other types of treatment research, since client
      treatment interactions are hypothesized to be moderated or mediated by specific
      treatment components. The role of process assessment in treatment matching
      research is examined using Project MATCH as an illustrative example. Four process
      domains, including dose of treatment, within-session treatment activities, the
      therapeutic alliance and extra-session activities, are described in terms of
      their role as mediators or moderators of treatment outcome and the perspectives
      by which they are assessed in Project MATCH.

PMID- 7722993
TI  - A chronological review of empirical studies matching alcoholic clients to
      treatment.
AB  - During the past 20 years researchers have become increasingly interested in
      exploring the benefits of differential assignment of alcoholics to treatments
      based on client-specific characteristics, rather than searching for a single
      "most effective" intervention for all clients. Thirty-one empirical studies on
      "client-treatment matching" are reviewed, particularly from the perspective of
      how research methodology in this area has evolved. In addition, general
      observations are provided on how research methodology on this topic can be
      further enhanced. Finally, several promising interactions between client
      characteristics and particular interventions are noted, based on empirical
      studies to date.

PMID- 7722994
TI  - Clinical applications: the transition from research to practice.
AB  - As validated and improved alcoholism treatment methods emerge from Project MATCH
      and other studies, a dedicated and systematic effort will be needed to
      incorporate them into ongoing programs, to monitor their success in real world
      settings and to make adjustments and refinements as needed. Accomplishing this
      involves responsibilities for both researchers and practitioners. A complex
      continuum of activities designed to move interventions from research to practice
      is common to all therapeutic areas, with a fundamental component being researcher
      provider interactions. Challenges include "debunking" myths; realistic
      evaluations of the feasibility of making changes in the treatment system;
      effective communication between providers and researchers; and proactive guidance
      from leaders who set standards of practice. Findings from relevant studies in
      alcoholism research can be assimilated into the treatment system with as little
      delay as possible as linkages between researchers and providers are strengthened.
      These linkages will be further strengthened by research in organizational,
      management and delivery mechanisms conducted by emerging applied research areas
      such as health services.

PMID- 7722995
TI  - Multisite clinical trials in alcoholism treatment research: organizational,
      methodological and management issues.
AB  - Multisite clinical trials have two major advantages over single-site studies: the
      large sample size of multisite studies allows for adequate statistical power and
      better representativeness of the population being studied. However, they are more
      complex to implement than single-site studies. This article reviews previous
      multisite clinical trials of alcohol abuse and alcoholism, reasons for selecting
      a multisite design, management of such studies, and some statistical issues.

PMID- 7722996
TI  - Designing studies to investigate client-treatment matching.
AB  - The process of designing studies of client-treatment matching involves a number
      of methodological complexities. Besides the large number of potential client
      characteristics and a range of possible outcome variables, a variety of treatment
      attributes can be matched including modality, intensity, duration, format,
      setting, therapist and goal. Hindsight matching designs (which can include
      hypothesis testing) examine interactions between client characteristics and
      treatments to which they were not intentionally matched. Foresight matching
      designs involve a prospective experimental test of a matching hypothesis,
      comparing the outcomes of cases matched by specific decision rules with other
      cases not so matched. Under certain conditions, these hindsight and foresight
      matching designs are logically equivalent. Mathematical modeling of clinical
      judgment offers yet another promising avenue for future studies of matching
      schemas. Glaser's core-shell strategy provides a practical model for implementing
      clinical systems and research on matching within ongoing services.

PMID- 7722997
TI  - Issues in the development of client-treatment matching hypotheses.
AB  - This article discusses observations and insights that were gained in the course
      of critiquing the a priori client-treatment matching hypothesis that were
      developed for Project MATCH. A matching taxonomy is offered that differentiates
      eight types of ordinal and disordinal interactions and discusses their clinical
      and substantive implications. Previously reported alcohol treatment studies are
      used to illustrate many of these. Various issues in matching studies, such as
      power versus complexity, prediction versus explanation, matches versus mismatches
      and capitalization versus compensation, are discussed. Selective issues in
      choosing treatment and client-matching variables as they affect matching
      hypotheses are also addressed. The importance of developing a putative "causal
      chain" for testing the theory underlying matching processes is explicated and a
      procedure for testing this causal chain is outlined.

PMID- 7722998
TI  - Alcoholism treatment matching research: methodological and clinical issues.
AB  - Client-treatment matching is an area receiving increased attention both in
      clinical practice and research with alcoholism. While the notion of potentially
      improving treatment outcomes by matching has been suggested for some time, there
      are a number of methodological and practical barriers that have impeded progress
      in the development of theoretically and clinically relevant matching models. This
      article provides an overview of the potential benefits of matching, the
      methodological factors that increase the complexity of research in this area, and
      some of the clinical barriers that make implementation more difficult. This
      overview also serves to introduce this special issue of the Journal of Studies on
      Alcohol, which examines in more detail each of the methodological issues involved
      in clinical research on treatment matching. While these methodological issues
      present unique challenges to the clinical researcher, the potential benefits of
      matching appear promising and should serve to motivate clinicians and researchers
      to pursue continued work in this area.

PMID- 7722999
TI  - Alcoholism treatment matching research: methodological and clinical approaches.

PMID- 7723000
TI  - Issues in the development of subject recruitment strategies and eligibility
      criteria in multisite trials of matching.
AB  - Decision-making in selecting and recruiting subjects for treatment matching
      research is a complex process involving conceptual, methodological and practical
      considerations. In selecting clients, concerns arise about whether the criteria
      will produce a subject population that is (1) relevant to the dimensions
      associated with the treatment matching, (2) representative of persons typically
      seen in alcohol treatment settings and, for practical purposes, (3) able or
      willing to comply with the requirements of the study protocol. Also, in order to
      fulfill sampling requirements, it may be necessary to employ a variety of
      creative outreach methods. However, these recruitment mechanisms can pose
      additional logistical and methodological problems for the research. This article
      focuses on various issues arising in the selection and recruitment of subjects in
      matching research. Project MATCH serves to highlight issues related to client
      eligibility and recruitment and to discuss effective strategies for resolving
      these matters.

PMID- 7723001
TI  - Ensuring balanced distribution of prognostic factors in treatment outcome
      research.
AB  - In comparative or matching research involving two or more treatments, the
      equivalence of the patient groups is of critical importance. In the past,
      equivalence has either been imposed by matching or balancing, or has been assured
      statistically by randomization. Matching and balancing, while useful in many
      contexts, nonetheless have important limitations, as does simple randomization.
      In recent years, a new tool has been developed that represents a compromise
      between balancing and randomization. This method, urn randomization, gives
      clinical investigators new options for improving the credibility of studies at a
      relatively modest cost. Urn randomization is randomization that is systematically
      based in favor of balancing. It can be used with several covariates, both
      marginally and jointly, producing optimal multivariate equivalence of treatment
      groups for large sample sizes. It preserves randomization as the primary basis
      for assignment to treatment and is less susceptible to experimenter bias or
      manipulation of the allocation process by staff than is balancing. Disadvantages
      include the fact that it is more difficult to implement, and that it violates the
      simple probability model of simple randomization. A number of research studies on
      addictions, including client-treatment matching trials, have used urn
      randomization. A summary of the mechanics of urn randomization is presented, and
      guidelines for its use in treatment studies are discussed.

PMID- 7723002
TI  - Classical analytical methods for detecting matching effects on treatment outcome.
AB  - This article presents a classical approach for analyzing repeated measures
      designs with specific application to treatment matching studies. The generic
      treatment matching hypothesis is formulated under the multivariate general linear
      model, transforming the dependent variables to account for the repeated measures
      structure of the data. Issues of primary importance in the use of this approach
      (such as correcting for inflated Type I error and robustness of statistical tests
      to parametric assumptions) are discussed. The article concludes with an
      assessment of the strengths and weaknesses of this approach compared with
      alternative approaches.

PMID- 7723003
TI  - Alternative analytical methods for detecting matching effects in treatment
      outcomes.
AB  - Project MATCH presented a unique opportunity for a team of statisticians, data
      analysts and content experts to come together and explore the strengths and
      weaknesses of the application of various statistical models to the data of the
      type being collected in this large trial. The following models were evaluated:
      multilevel models, event history models, multiple were structural equation
      modeling, time series models, ordinal repeated measures designs and generalized
      estimating equations. No one model was found to be the perfect solution and each
      seemed to have something to recommend it. Future research on these methods will
      shed light on many issues raised. It is hoped that alcohol researchers will find
      useful guidelines within this chapter as they plan and carry out their studies.

PMID- 7723004
TI  - Assessment issues and strategies in alcoholism treatment matching research.
AB  - Sensitive and comprehensive client assessment entails complex conceptual and
      methodological considerations. Such activity is at the heart of matching clients
      to appropriate treatments. This article begins by specifying the goals and
      functions of assessment to support matching. This is followed by a discussion of
      the strategies employed in Project MATCH to identify matching and outcome
      variables. The assessment battery used in Project MATCH is next described.
      Finally, an overview of issues surrounding administration of assessment measures
      is provided. Particular attention is given to the topics of sequencing and timing
      of measures.

PMID- 7723005
TI  - Change in amniotic fluid index after amniotomy during first stage of labor.

PMID- 7723006
TI  - Treatment results in laryngeal carcinoma: a study of 109 patients.

PMID- 7723007
TI  - There is an alternative to litigation.

PMID- 7723008
TI  - Laryngeal carcinoma--a relationship to tobacco and alcohol use.

PMID- 7723009
TI  - Bacteriophage T4 gene 17 amplification mutants: evidence for initiation by the T4
      terminase subunit gp16.
AB  - Bacteriophage T4 genes 16 and 19 containing the 24 bp homology regions that
      recombine to form Hp17 mutants were cloned into plasmids. When the two homology
      sequences were cloned either together into one or separately into two compatible
      plasmids, a polymerase chain reaction assay showed that recombination occurred in
      vivo. The recombinant sequence was identical with that found in T4 phage Hp17
      mutants, and was produced in recombination-deficient Escherichia coli. Mutational
      analysis revealed a requirement for functional gene 16 but not gene 17 to
      recombine the sequences. Moreover, gp16, the terminase small subunit, was
      required, since an amber gene 16 produced the recombinant sequence only when
      suppressed. Mutations in the gene 16 recombination sequence (3GA and 15TG) that
      eliminated Hp17 formation in T4 phage increased the synthesis of the large
      terminase subunit, gp17 in T4 infections, suggesting gp16 interaction with this
      site. gp16 binding to gene 16 and gene 19 pac-like sites may synapse the
      homologous sequences to lead to Hp17 mutant formation, and this suggests a
      synapsis mechanism for control of T4 DNA maturation and concatemer processing in
      packaging.

PMID- 7723010
TI  - Structural studies of HIV-1 Tat protein.
AB  - Tat (trans-activator) proteins are early RNA binding proteins regulating
      lentiviral transcription. These proteins are necessary components in the life
      cycle of all known lentiviruses, such as the human immunodeficiency viruses (HIV)
      or the equine infectious anemia virus (EIAV). Tat proteins are thus ideal targets
      for drugs intervening with lentiviral growth. The consensus RNA binding motif
      (TAR, trans-activation responsive element) of HIV-1 is well characterized.
      Structural features of the 86 amino acid HIV-1, Zaire 2 isolate (HV1Z2) Tat
      protein in solution were determined by two dimensional (2D) nuclear magnetic
      resonance (NMR) methods and molecular dynamics (MD) calculations. In general,
      sequence regions corresponded to structural domains of the protein. It exhibited
      a hydrophobic core of 16 amino acids and a glutamine-rich domain of 17 amino
      acids. Part of the NH2 terminus, Val4 to Pro14, was sandwiched between these
      domains. Two highly flexible domains corresponded to a cysteine-rich and a basic
      sequence region. The 16 amino acid sequence of the core region is strictly
      conserved among the known Tat proteins, and the three-dimensional fold of these
      amino acids of HV1Z2 Tat protein was highly similar to the structure of the
      corresponding EIAV Tat domain. HV1Z2 Tat protein contained a well defined COOH
      terminal Arg-Gly-Asp (RGD) loop similar to the recently determined decorsin RGD
      loop.

PMID- 7723011
TI  - SCOP: a structural classification of proteins database for the investigation of
      sequences and structures.
AB  - To facilitate understanding of, and access to, the information available for
      protein structures, we have constructed the Structural Classification of Proteins
      (scop) database. This database provides a detailed and comprehensive description
      of the structural and evolutionary relationships of the proteins of known
      structure. It also provides for each entry links to co-ordinates, images of the
      structure, interactive viewers, sequence data and literature references. Two
      search facilities are available. The homology search permits users to enter a
      sequence and obtain a list of any structures to which it has significant levels
      of sequence similarity. The key word search finds, for a word entered by the
      user, matches from both the text of the scop database and the headers of
      Brookhaven Protein Databank structure files. The database is freely accessible on
      World Wide Web (WWW) with an entry point to URL http: parallel scop.mrc
      lmb.cam.ac.uk magnitude of scop.

PMID- 7723012
TI  - Application of 1H NMR chemical shifts to measure the quality of protein
      structures.
AB  - We have developed a program that can calculate proton NMR chemical shifts for
      proteins, using a set of co-ordinates provided for example from an X-ray or NMR
      structure. When applied to NMR structures, agreement between calculated and
      observed shifts is generally of the same quality as that for crystal structures
      of resolution between 2.0 and 3.0 A. There is a rather weak correlation between
      standard deviation (SD) and the number of NMR constraints per residue, but none
      with the root-mean-square deviation of one NMR structure from another. Where
      minimised averaged structures are present, they have about the same SD as the
      population from which they were taken. Refinement methods such as energy
      minimisation and the use of relaxation matrices and back calculation produce
      little or no improvement in SD. The calculation has several applications,
      particularly as an independent means of measuring the quality of a structure
      (either in the crystal or in solution), and in identifying possible assignment
      errors.

PMID- 7723013
TI  - ATP hydrolysis is required for DNA cleavage by EcoPI restriction enzyme.
AB  - The type III restriction endonuclease EcoPI, coded by bacteriophage P1, cleaves
      unmodified DNA in the presence of ATP and magnesium ions. We show that purified
      EcoPI restriction enzyme fails to cleave DNA in the presence of non-hydrolyzable
      ATP analogs. More importantly, this study demonstrates that EcoPI restriction
      enzyme has an inherent ATPase activity, and ATP hydrolysis is necessary for DNA
      cleavage. Furthermore, we show that the progress curve of the reaction with EcoPI
      restriction enzyme exhibits a lag which is dependent on the enzyme concentration.
      Kinetic analysis of the progress curves of the reaction suggest slow transitions
      that can occur during the reaction, characteristic of hysteretic enzymes. The
      role of ATP in the cleavage mechanism of type III restriction enzymes is
      discussed.

PMID- 7723014
TI  - Kid, a small protein of the parD stability system of plasmid R1, is an inhibitor
      of DNA replication acting at the initiation of DNA synthesis.
AB  - The Kid and Kis proteins are the killer component and the antagonist belonging to
      parD, a killer stability system of plasmid R1. The Kid and Kis proteins have been
      purified, the second one as a C-LYT-Kis fusion that conserves the antagonistic
      activity of the Kis protein, but not its auto-regulatory potential. Kid inhibits
      in vitro replication of CoEl to a basal level without altering the superhelicity
      of the template but it does not substantially affect in vitro replication of P4,
      a DnaA, DnaB, DnaC and DnaG-independent replicon. Kid inhibits lytic induction of
      a lambda, prophage, but this inhibition can be neutralized by excess DnaB. In
      addition, a multicopy dnaB recombinant, but not a multicopy dnaG recombinant,
      prevents the toxicity associated with this protein. Inhibition of ColE1
      replication by Kid in vitro is prevented by the C-LYT-Kis protein. Functional
      analysis indicates that the antagonistic activity of Kis is independent of its
      activity as a co-regulator of the parD promoter. It is also shown that C-LYT-Kis
      and Kid interact, forming a tight complex. These results strongly suggest that
      the toxicity of the kid protein is due to inhibition of DnaB-dependent DNA
      replication, and that direct protein-protein interactions are involved in the
      neutralization of the activity of the killer protein by the antagonist.

PMID- 7723015
TI  - A functional analysis of the inverted repeat of the gamma delta transposable
      element.
AB  - We have constructed a library of point mutants of the 35 base-pair terminal
      inverted repeat (IR) of the bacterial transposon gamma delta, a member of the Tn3
      family of transposable elements. The effect of the mutant ends, both on the
      immunity conferred on an IR-containing target plasmid and on the transposition of
      model transposons, was determined. The region important for immunity was shown to
      be a 30 base-pair stretch of DNA, running from G8 and A9 to G38; mutations in the
      outermost seven or eight base-pairs did not significantly affect immunity.
      Positions at which mutations disrupted immunity chiefly coincided with positions
      previously determined to constitute three segments of the IR with which gamma
      delta tranposase protein interacts via major groove contacts. We conclude that
      sequence-specific binding contacts between gamma delta transposase and its
      cognate IR are limited to a specific subset of positions (those sensitive to
      mutation in the immunity assay) within this 30 base-pair region. We found that
      the innermost of the three major groove contact regions was the most susceptible
      to mutation, while the outermost was the least. Indications of minor groove
      contacts were also found. Very few point mutations within the 30 base-pair
      sequence-specific binding region had much effect on transposition when the mutant
      ends were in the "wild-type" context with the adjacent integration host factor
      (IHF) binding site. However, deletion of the IHF site, in some cases, revealed a
      transposition defect, suggesting that for transposition (but not immunity), IHF
      transposase cooperation can largely overcome the effects of reduced transposase
      binding. Although the outer seven base-pairs were not important for immunity,
      mutations in the outer three or four eliminated or reduced transposition
      activity, suggesting that these positions are involved in a step in transposition
      that follows transposase binding.

PMID- 7723016
TI  - NCA2, a second nuclear gene required for the control of mitochondrial synthesis
      of subunits 6 and 8 of ATP synthase in Saccharomyces cerevisiae.
AB  - Respiratory-competent nuclear mutants have been isolated which presented a
      cryosensitive phenotype on a non-fermentable carbon source, due to a dysfunction
      of the mitochondrial F1-Fo ATP synthase. This defect results from an alteration
      of the mtDNA-encoded protein synthesis level of subunits 6 and 8 of the Fo
      sector, due to the simultaneous presence of a mutation in two unlinked nuclear
      genes. These mutations promote a modification of the expression of the
      cotranscript ATP8-ATP6 (formerly denoted AAP1-OL12): this mRNA undergoes a
      maturation at a unique site reaching to two cotranscripts of 5.2 and 4.6 kb in
      length: in the mutant, the relative amount of 5.2 kb cotranscript was greatly
      lowered. NCA2 was isolated from a wild-type yeast genomic library by genetic
      complementation. The relative level of the 5.2 kb transcript, as the synthesis of
      subunits 6 and 8, was partly restored in the transformed strain. A 1848
      nucleotide open reading frame was depicted that encoded an amphiphilic protein of
      70,816 Da. Disruption of chromosomal DNA within the reading frame promoted a
      dramatic decrease of the 5.2 kb mRNA but did not abolish the respiratory
      competence of a wild-type strain. Hybridization analyses indicated that NCA2 is
      located on chromosome XVI and produces a single 2750 base transcript.

PMID- 7723017
TI  - Interaction of Fc gamma receptor type IIIB with complement receptor type 3 in
      fibroblast transfectants: evidence from lateral diffusion and resonance energy
      transfer studies.
AB  - To explore potential inter-receptor interactions between Fc gamma RIIIB, a GPI
      linked protein, and the leukocyte integrin CR3, we have prepared transfected 3T3
      fibroblast cell lines expressing Fc gamma RIIIB, CR3, or both Fc gamma RIIIB and
      CR3. We test the hypothesis that Fc gamma RIIIB and CR3 are physically associated
      in membranes using fluorescence recovery after photobleaching (FRAP) and
      resonance energy transfer (r.e.t.) microscopy. Cells expressing Fc gamma RIIIB
      alone displayed a diffusion coefficient (D) of 3.4 x 10(-9) (+/- 2.9 x 10(-9)
      cm2/second and a mobile fraction (m.f.) of 0.73 (+/- 0.10). In contrast, Fc gamma
      RIIIB exhibited D = 2.5 x 10(-9) (+/- 1.4 x 10(-9) cm2/second (n.s.) and a m.f.
      of 0.48 (+/- 0.08) (p < 0.01) on cells expressing both Fc gamma RIIB and CR3,
      thus indicating that co-expression of CR3 constrains the lateral diffusion of Fc
      gamma RIIIB. To further test for a direct physical interaction between these gene
      products, (r.e.t.) microscopy was performed. Donor-labeled anti-CR3 and acceptor
      labeled anti-Fc gamma RIIIB on cells expressing both receptors yielded a r.e.t.
      photon count rate of 8.9(+/- 6.4) kilocounts/second (kC/s), whereas CR3-to-CR3
      measurements gave 1.6(+/- 0.6) kC/s (p < 0.01). Moreover, the addition of
      exogenous agents such as N-acetyl-D-glucosamine, but not indomethacin, diminished
      the magnitude of these interactions in transfectant membranes. These data support
      the notion that a subpopulation of Fc gamma RIIIB is physically associated with
      CR3 and that this association can be affected by exogeneous compounds.

PMID- 7723018
TI  - Mutational analysis of the sequence-specific recombination box for amplification
      of gene 17 of bacteriophage T4.
AB  - Bacteriophage T4 gene 17 amplification mutants Hp17 that carry two to six tandem
      repeats of the genes 17-18 region were isolated by growth of gene 17 amber
      mutants on ochre suppressor strains of Escherichia coli. These mutants arise from
      an initial sequence-specific recombination between two GCTCA sequences in a 24 bp
      imperfect homology box in genes 16 and 19. The initial recombination occurred in
      the wild-type phage T4 population, as shown by polymerase chain reaction, at a
      frequency of about 10(-6), which is consistent with the frequency of mutant
      isolation. T4 phage with mutations of the 3rd, 6th, 9th, 12th, or 15th positions
      in the 24 bp box of gene 16 either failed to produce gene amplification mutant
      Hp17 or produced gene amplification mutants from an initial recombination at
      other regions. Among the mutants that failed to produce gene amplification
      mutants, the initial recombination generally occurred at lower frequencies at
      either the GCTCA sequence or other sequences. Since the gene amplification
      mutations are eliminated or shifted to different sequences by base changes that
      increase as well as decrease homology, the predominant recombination event
      between the gene 16 and 19 recombination boxes appears to be sequence-dependent
      rather than homology-dependent.

PMID- 7723019
TI  - Structural transitions during bacteriophage HK97 head assembly.
AB  - Bacteriophage HK97 builds its head shell from a 42 kDa major head protein, but
      neither this 42 kDa protein nor its processed, 31 kDa form is found in the mature
      head. Instead, each of the major head-protein subunits is covalently cross-linked
      into oligomers of five, six or more by a protein cross-linking reaction that
      occurs both in vivo and in vitro. Mutants that block prohead maturation lead to
      the accumulation of one of two types of proheads, termed Prohead I and Prohead
      II. Prohead I is assembled from about 415 copies of the 42 kDa (384 amino acids)
      protein subunit and accumulates in infections by mutant amU4. Following assembly,
      the N-terminal 102 amino acids of each subunit are removed, leaving a prohead
      shell constructed of 31 kDa subunits, called Prohead II, which accumulates in
      infections by mutant amC2. During DNA packaging, when the prohead shell expands,
      all of the head protein subunits become covalently cross-linked to other
      subunits. Purified Prohead II (or, less completely, Prohead I) becomes cross
      linked in vitro in response to any of a number of conditions that induce shell
      expansion, including conditions commonly used for protein analysis. In vitro
      cross-linking occurs efficiently in the absence of added cofactors of enzymes,
      and we propose that cross-linking is catalyzed by shell subunits themselves.
      Shell expansion is easily monitored by observing a decrease in electrophoretic
      mobility of Prohead II in agarose gels. Using the mobility shift in agarose gel
      to monitor expansion and SDS/gel electrophoresis to monitor cross-linking in
      vitro, we find that expansion precedes and is required for cross-linking, and we
      propose that expansion triggers the cross-linking reaction. Comparison of
      peptides isolated from Prohead II and in vitro cross-linked Prohead II shows a
      single altered major cross-link peptide in which a lysine, originating from
      lysine169 of the protein sequence, is linked to asparagine356, presumably derived
      from the neighboring subunit. Examination of the cross-link-containing peptide by
      mass spectrometry shows that the cross-link bond is an amide between the side
      chains of the lysine and the asparagine residues.

PMID- 7723020
TI  - Genetic basis of bacteriophage HK97 prohead assembly.
AB  - We report studies to determine which bacteriophage genes are required for
      assembly of phage HK97 proheads and what roles they play. We identify the gene
      encoding the major capsid protein of phage HK97 and report its DNA sequence,
      together with the DNA sequences of the two genes immediately upstream from it.
      When the capsid protein is expressed from a plasmid in the absence of other phage
      encoded proteins, it assembles, with good efficiency and accuracy into prohead
      like structures composed of the unprocessed 42 kDa capsid protein. No separately
      encoded scaffolding protein is required for this assembly. If the 25 kDa product
      of the next gene upstream is co-expressed with the capsid protein, the prohead
      structures that are produced undergo the normal morphogenetic cleavage, which
      removes 102 amino acids from the N terminus of each subunit, leaving 31 kDa
      subunits. The 25 kDa protein is therefore probably a phage-encoded protease. The
      third gene, upstream from the protease gene, encodes the portal protein. Presence
      of the portal protein is not required for assembly of the capsid protein.
      Analysis of the phenotypes of four single amino acid-substitution mutants in the
      capsid-protein gene leads to several insights into the functions of the capsid
      protein and its interactions with the putative protease.

PMID- 7723021
TI  - Structural analysis of peptides encompassing all alpha-helices of three
      alpha/beta parallel proteins: Che-Y, flavodoxin and P21-ras: implications for
      alpha-helix stability and the folding of alpha/beta parallel proteins.
AB  - In an attempt to delineate the early folding events of structurally related
      proteins with no sequence homology, peptides including all five alpha-helices of
      three alpha/beta parallel open-sheet proteins, Che-Y, flavodoxin and P21-ras,
      have been analyzed by circular dichroism (far-UV CD) and nuclear magnetic
      resonance (NMR) in water and 30% (v/v) trifluoroethanol (TFE). Comparison between
      the helical content estimations from far-UV CD and the results from the NMR
      analysis renders a reasonably good qualitative correlation, indicating that the
      same phenomenon is underlined by both methods. Helix limits, as indicated by the
      existence of (i,i + 3) nuclear Overhauser effect (NOE) cross-correlations and
      significant up-field conformational shifts of the C alpha H protons, are
      practically coincident with those in the folded protein. On the other hand, the
      conformation of the side-chains differs markedly from those in the folded
      protein. Observation of NOE cross-correlations between pairs of residues at
      positions i,i + 3 has been used to statistically quantify free energies of i,i +
      3 side-chain-side-chain interactions between the different pairs of residues in
      an alpha-helix. This analysis indicates that interactions between hydrophobic
      side-chains seem to be quite favorable for helix formation. The behaviour in
      aqueous solution of the structural equivalent peptides for the three proteins is
      quite unrelated except for the peptides corresponding to helices two and five. We
      postulate that, in the alpha/beta parallel proteins, those helices that join two
      beta-strands flanking another non-consecutive beta-strand should not be stable
      for folding reasons.

PMID- 7723022
TI  - The order of secondary structure elements does not determine the structure of a
      protein but does affect its folding kinetics.
AB  - We have analyzed the structure, stability and folding kinetics of circularly
      permuted forms of alpha-spectrin SH3 domain. All the possible permutations
      involving the disruption of the covalent linkage between two beta-strands forming
      a beta-hairpin have been done. The different proteins constructed here fold to a
      native conformation similar to that of wild-type protein, as demonstrated by
      nuclear magnetic resonance and circular dichroism. Although all the mutants have
      similar stabilities (they are 1 to 2 kcal mol-1 less stable than the wild-type)
      their rate constants for folding and unfolding are quite different. Protein
      engineering, in combination with kinetics indicates that the folding pathway has
      been changed in the circularly permuted proteins. We conclude that neither the
      order of secondary structure elements, nor the preservation of any of the beta
      hairpins present in this domain, is crucial for the ability of the polypeptide to
      fold, but they influence the folding and unfolding kinetics and could determine
      its folding pathway.

PMID- 7723023
TI  - Stability of alpha-helices in a molten globule state of cytochrome c by hydrogen
      deuterium exchange and two-dimensional NMR spectroscopy.
AB  - To distinguish between intrinsically stable helices and those stabilized by the
      protein three-dimensional structure, we report the hydrogen-deuterium exchange
      (H2H) rates of 29 amide protons of ferricytochrome c in a molten globule state
      (at 35 degrees C, pH 2.0 with 0.5 M KCl), monitored by 2D-NMR. The results of the
      H2H-exchange experiments have been analyzed to calculate the protection factors.
      The helices were not uniformly stable and amide protons of residues belonging to
      the N and C-terminal helices had high protection factors. The protection factors
      of amide protons involved in the 50's helix were low, and could not be determined
      quantitatively. In the 60's helix we found two amide protons with protection
      factors comparable to those of the N and C-terminal helices. These results,
      compared with previously reported intrinsic helicities of peptide fragments,
      indicate that the relative helicities of isolated fragments are not directly
      reflected in the stability of the helices in the molten globule state, even
      though this state has no rigid tertiary structure. This suggests that loose
      interactions between helices are present in the molten globule state of
      cytochrome c, and that they are essential for keeping the helicity of the helical
      segments. The loose tertiary interactions discussed here differ from the usual
      tertiary interaction found in the native state in that the specific
      interdigitization between side-chains is absent.

PMID- 7723024
TI  - Structure refinement of the glucocorticoid receptor-DNA binding domain from NMR
      data by relaxation matrix calculations.
AB  - The solution structure of the glucocorticoid receptor (GR) DNA-binding domain
      (DBD), consisting of 93 residues, has been refined from two and three-dimensional
      NMR data using an ensemble iterative relaxation matrix approach followed by
      direct NOE refinement with DINOSAUR. A set of 47 structures of the rat GR
      fragment Cys440-Arg510 was generated with distance geometry and further refined
      with a combination of restrained energy minimization and restrained molecular
      dynamics in a parallel refinement protocol. Distance constraints were obtained
      from an extensive set of NOE build-up curves in H2O and 2H2O via relaxation
      matrix calculations (1186 distance constraints from NOE intensities, 10 phi and
      22 chi 1 dihedral angle constraints from J- coupling data were used for the
      calculations). The root-mean-square deviation values of the 11 best structures on
      the well-determined part of the protein (Cys440 to Ser448, His451 to Glu469 and
      Pro493 to Glu508) are 0.60 A and 1.20 A from the average for backbone and all
      heavy atoms, respectively. The final structures have R-factors around 0.40 and
      good stereochemical qualities. The first zinc-coordinating domain of the GR DBD
      is very similar to the crystal structure with a root-mean-square difference of
      1.4 A. The second zinc-coordinating domain is still disordered in solution. No
      secondary structure element is found in this domain in the free state. As
      suggested by crystallographic studies on the estrogen receptor DBD-DNA and GR DBD
      DNA complexes, part of this region will form a distorted helix and the D-box will
      undergo a conformational change upon cooperative binding to DNA.

PMID- 7723025
TI  - Ligand-induced changes in the conformational stability of bovine trypsinogen and
      their implications for the protein function.
AB  - Bovine trypsinogen was used as a model protein for studying changes in the
      conformational stability induced by pH or binding of the calcium ion.
      Spectrophotometrically monitored thermal unfolding of trypsinogen and beta
      trypsin in the acidic pH range yielded substantial differences in the stability
      parameters. Compared to beta-trypsin, trypsinogen exhibits lower enthalpy of
      denaturation delta Hden, higher denaturational heat capacity change delta Cp,den,
      but very similar temperature of denaturation Tden. pH-dependence of the
      conformational stability of the ligand-free trypsinogen, measured also by GdnCl
      induced unfolding, is bell shaped with the maximum free energy of unfolding delta
      Gden = 10.9 kcal/mole at pH 5.5 (4.5 pH units below its isoelectric point). At pH
      8.3 the conformational stability of the zymogen drops to delta Gden = 3.2
      kcal/mole, but increases by delta delta Gden = 6.1 kcal/mole in the presence of
      Ca2+. This significant stabilization of the zymogen by the calcium ion is also pH
      dependent. To assess the effect of Ca2+ on the trypsinogen molecule, the
      spectrophotometric titrations and NOESY spectra were carried out. Based on the
      structural analysis, the long range effects between Ca2+-->Ile73-->Trp141 and the
      interdomain His40-Asp194 ion pair are proposed to be partially responsible for
      trypsinogen stabilization. Additionally, the steady-state parameters for
      hydrolysis of the oligopeptide amide substrate catalysed by free trypsinogen, its
      complexes with Ca2+ and the IleVal dipeptide and by beta-trypsin were measured.
      It appears that in the pH range 5.5 to 8.3 the stability and the catalytic
      activity/ligand binding properties are fully separated. Whereas the deprotonation
      of His57 accounts for the increase of kcat/km parameter, deprotonation of His40
      is involved in the huge decrease of the conformational stability. Similarly, a
      large stabilization by the calcium ion is not accompanied by changes in enzymatic
      activity. Presented data are encouraging for an enzyme design directed toward
      improved stability.

PMID- 7723026
TI  - Three-dimensional structure of chemotactic Che Y protein in aqueous solution by
      nuclear magnetic resonance methods.
AB  - The three-dimensional structure of chemotactic Che Y protein from Escherichia
      coli in aqueous solution has been determined by nuclear magnetic resonance (NMR)
      spectroscopy combined with restrained molecular dynamics calculations. A total of
      20 converged structures were computed from 1545 conformationally relevant
      distance restraints derived from 1858 unambiguously assigned NOE cross
      correlations. The resulting average pairwise root-mean-square deviation is 1.03 A
      for the backbone atoms and 1.69 A for all heavy atoms. If residues in the regions
      structurally least defined (1 to 5, 47 to 50, 76 to 79, 88 to 91 and 124 to 129)
      are excluded from the analysis, the root-mean-square deviations are reduced to
      0.53 A and 1.23 A, respectively. The solution structure is closely similar to the
      refined X-ray crystal structure, except in the regions found to be less defined
      by NMR spectroscopy. The root-mean-square deviation between the average solution
      structure and the X-ray crystal structure is 0.92 A for the backbone residues (2
      to 129). The highly refined solution structure determined herewith provides an
      essential background to delineate functionally important conformational changes
      brought about by different effectors.

PMID- 7723027
TI  - Three-dimensional structure of halorhodopsin at 7 A resolution.
AB  - Two-dimensional crystalline patches containing the light-driven chloride pump,
      halorhodopsin, appear to form spontaneously in the cell membrane of an
      overproducing strain of Halobacterium. The three-dimensional structure (space
      group p42(1)2, a = 102 A) has been analysed by electron cryo-microscopy of tilted
      specimens. The map shows that halorhodopsin (HR) has an arrangement of seven
      transmembrane helices similar to that found in the related proton pump
      bacteriohodopsin (BR). The orientation of the polypeptide framework of HR in the
      membrane is rotated by 3 degrees relative to BR about an axis in the plane and
      the intramolecular space between the helices BC FG, which line the cytoplasmic
      half channel, appears slightly larger in HR than in BR, as would be expected for
      a chloride channel. The crystals of HR were too small for electron diffraction
      analysis of tilted specimens, so both the amplitudes and the phases of the
      Fourier components were obtained from images. This required anisotropic scaling
      of the image amplitudes in addition to correction for the defocus phase contrast
      transfer function. The procedure of rescaling the data (in this case roughly
      equivalent to sharpening with a temperature factor of-490) to compensate for a
      variety of image and crystal defects may also prove useful in the analysis of
      other structures for which no prior knowledge of a homologous structure exists
      and for which only small crystals can be obtained.

PMID- 7723028
TI  - An RBD that does not bind RNA: NMR secondary structure determination and
      biochemical properties of the C-terminal RNA binding domain from the human U1A
      protein.
AB  - We have obtained backbone 1H, 15N, and 13C assignments and determined the
      secondary structure and folding topology of the C-terminal RNA-binding domain
      (RBD) of the human U1A protein. The secondary structure derived from NOE data is
      in excellent agreement with the predicted structure from the 1H and 13C chemical
      shift indices. This 88 amino acid domain exhibits a beta alpha beta-beta alpha
      beta folding pattern, with conserved RNP1 and RNP2 sequences located in two
      adjacent strands of a four-strand antiparallel beta-sheet. This global folding
      pattern is typical of this class of RNA binding proteins. Although this domain
      contains residues that are conserved in all RBDs, its RNA binding properties are
      very unusual. RNA binding studies show that this domain does not bind U1, U2 or
      U5 snRNA, an RNA hairpin, rA16, rU16, rC16 or rA3U3GUA4, nor does it show
      significant association to populations of random sequence RNAs.

PMID- 7723029
TI  - The zinc coordination site of the bacteriophage Mu translational activator
      protein, Com.
AB  - The bacteriophage Mu Com protein is a small "zinc finger-like" protein that binds
      a specific site in com-mom operon mRNA and activates translation of the mom open
      reading-frame. Com contains six cysteine and five histidine residues that have
      the potential to form several alternative zinc-finger-like motifs. We have used
      oligonucleotide site-directed mutagenesis to individually alter each of these
      amino acids (Cys to Ser, and His to Asn or Gln) and tested the various forms of
      Com for their ability to function in vivo. We observed that mutation of any one
      of the four N-terminal cysteine residues (Cys-6, 9, 26 or 29) resulted in loss of
      Com activity. The Com protein requires zinc in order to fold into its functional
      tertiary structure, as demonstrated by characteristic 1H nuclear magnetic
      resonance (NMR) chemical shifts. 1H chemical shifts revert to random coil values
      in the presence of the metal chelator EDTA. The metal-binding specificity and
      thermal stability of Com also has been investigated using 1H NMR. We report the
      use of 113Cd NMR, 1H-113Cd heteronuclear spin-echo difference spectroscopy HSED
      and Zn extended X-ray absorption fine structure spectroscopy EXAFS to determine
      the zinc/protein stoichiometry as 1:1 and the ligand environment as
      tetrathiolate. Comparative NMR spectra of Com mutants C6S and C39S suggest
      position 6 is involved in zinc coordination, while position 39 is not metal
      liganded. These studies indicate that the metal coordination, site of Com is a
      four-cysteine complex, involving residues 6, 9, 26 and 29.

PMID- 7723030
TI  - Functional significance of arginine 15 in the active site of human class alpha
      glutathione transferase A1-1.
AB  - Arg15 is a conserved active-site residue in class Alpha glutathione transferases.
      X-ray diffraction studies of human glutathione transferase A1-1 have shown that N
      epsilon of this amino acid residue is adjacent to the sulfur atom of a
      glutathione derivative bound to the active site, suggesting the presence of a
      hydrogen bond. The phenolic hydroxyl group of Tyr9 also forms a hydrogen bond to
      the sulfur atom of glutathione, and removal of this hydroxyl group causes partial
      inactivation of the enzyme. The present study demonstrates by use of site
      directed mutagenesis the functional significance of Arg15 for catalysis. Mutation
      of Arg15 into Leu reduced the catalytic activity by 25-fold, whereas substitution
      by Lys caused only a threefold decrease, indicating the significance of a
      positively charged residue at position 15. Mutation of Arg15 into Ala or His
      caused a substantial reduction of the specific activity (200 or 400-fold,
      respectively), one order of magnitude more pronounced than the effect of the Tyr9
      ->Phe mutation. Double mutations involving residues 9 and 15 demonstrated that
      the effects of mutations at the two positions were additive except for the
      substitution of His for Arg15, which appeared to cause secondary structural
      effects. The pKa value of the phenolic hydroxyl of Tyr9 was determined by UV
      absorption difference spectroscopy and was found to be 8.1 in the wild-type
      enzyme. The corresponding pKa values of mutants R15K, R15H and R15L were 8.5, 8.7
      and 8.8, respectively, demonstrating the contribution of the guanidinium group of
      Arg15 to the electrostatic field in the active site. Addition of glutathione
      caused an increased pKa value of Tyr9; this effect was not obtained with S
      methylglutathione. These results show that Tyr9 is protonated when glutathione is
      bound to the enzyme at physiological pH values. The involvement of an Arg residue
      in the binding and activation of glutathione is a feature that distinguishes
      class Alpha glutathione transferases from members in other glutathione
      transferase classes.

PMID- 7723031
TI  - pH dependence of binding reactions from free energy simulations and macroscopic
      continuum electrostatic calculations: application to 2'GMP/3'GMP binding to
      ribonuclease T1 and implications for catalysis.
AB  - An approach is described for extending free energy calculations to take into
      account the pH dependence of the relative binding of ligands to an enzyme or
      other receptor protein. The method is based on the calculation of the free energy
      difference for a single protonation state via the thermodynamic cycle simulation
      approach followed by inclusion of all possible protonation states of the enzyme
      and the inhibitor by use of a macroscopic continuum dielectric (Poisson
      Boltzmann) model. A detailed formulation of the combined model is presented. It
      involves solution of the multiple equilibrium problem and makes use of the
      calculated pKa values of all titrating groups on both enzyme and ligand. The
      method is illustrated by calculations of the pH dependence of the differential
      binding of the inhibitors 2'GMP and 3'GMP to ribonuclease T1. A free energy
      simulation of the differential binding is made for a given protonation state of
      the enzyme and inhibitor. Although only qualitative agreement with experiment is
      obtained, the results provide insights concerning the interactions involved. The
      pH dependence of the binding is calculated by using the protonation state of the
      residues from the free energy simulation as the standard state for a Poisson
      Boltzmann calculation. Information is obtained concerning the pKa values of the
      titrating amino acids in the free, 2'GMP and 3'GMP bound enzyme forms of RNase T1
      and the difference in the pH dependence of the binding of 2'GMP and 3'GMP to
      RNase T1. The contributions of different types of interactions (e.g. protein
      residues versus solvent) to the free energy differences are examined. A free
      energy simulation of the pKa shift of Glu58 shows that it is important to
      consider both carboxyl oxygen atoms as possible protonation sites since they may
      behave very differently in a protein. It is found in the protein that the
      interactions with the solvent favor the neutral (protonated) state of Glu58. This
      contrasts sharply with the solution behavior, where the solvent favors the
      charged state. Analysis of the results shows that the interactions of bound water
      with other protein residues leads to the observed effect. Comparisons are made
      with a continuum calculation that uses the charged state employed in the free
      energy simulation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7723032
TI  - The effect of environment on the stability of an integral membrane helix:
      molecular dynamics simulations of surfactant protein C in chloroform, methanol
      and water.
AB  - A series of three molecular dynamics simulations at 300 K in explicit solvent
      environments of chloroform, methanol and water has been performed on the
      pulmonary surfactant lipoprotein, SP-C, comprising several consecutive valine
      residues in order to investigate the stability of the alpha-helical conformation.
      Two additional simulations were performed on truncated SP-C with a five-residue N
      terminal deletion at 300 K and 500 K in water, the high temperature run in order
      to increase the rate of peptide denaturation. Indications of destabilization
      appear in chloroform during 1 ns while the SP-C alpha-helix is remarkably stable
      during 1 ns in methanol and water. In particular the polyvalyl part comprising
      residues Val15 to Val21 remains intact even at elevated temperature, and the
      valines do not disrupt the alpha-helical conformation. The valyl-rotamer sampling
      is partly restricted. Unfolding takes place successively along the primary
      sequence starting from the C-terminal end. Factors affecting polypeptide
      stability in molecular dynamics simulations are addressed. The intrinsic helix
      forming tendency of valine residues and its dependence on the sequence context,
      and the role of the solvent environment in stabilizing or destabilizing an alpha
      helical fold, are discussed.

PMID- 7723033
TI  - Simple physical model of collagen fibrillogenesis based on diffusion limited
      aggregation.
AB  - Type I collagen is a rod-like protein which self-assembles in a regular array to
      form elongated fibrils. The process of fibril formation, termed fibrillogenesis,
      is driven by the increase in entropy associated with loss of water from the bound
      monomers. A model based on diffusion limited aggregation (DLA) was used to
      investigate some of the mechanisms involved in this process. The aggregates
      created in the model displayed several features in common with collagen fibrils
      including an elongated morphology and a preference for tip growth. Analysis of
      these aggregates revealed a linear relationship between mass and distance from
      the tip, consistent with experimental observations. Intrafibrillar fluidity was
      introduced into the model by using a surface diffusion term. This led to the
      formation of aggregates with more compact morphologies. These results strongly
      implicate the role of diffusion limited growth in collagen fibril formation.

PMID- 7723034
TI  - The folding mechanism of barstar: evidence for multiple pathways and multiple
      intermediates.
AB  - The mechanism of folding of the small protein barstar in the pre-transition zone
      at pH 7, 25 degrees C has been characterized using rapid-mixing techniques.
      Earlier studies had established the validity of the three-state US <--> UF <--> N
      mechanism for folding and unfolding in the presence of guanidine hydrochloride
      (GdnHCl) at concentrations greater than 2.0 M, where US and UF are the slow
      refolding and fast-refolding unfolded forms, respectively, and N is the fully
      folded form. It is now shown that early intermediates, IS1 and IS2 as well as a
      late native-like intermediate, IN, are present on the folding pathways of US, and
      an early intermediate IF1 on the folding pathway of UF, when barstar is refolded
      in concentrations of GdnHCl below 2.0 M. The rates of formation and disappearance
      of IN, and the rates of formation of N at three different concentrations of
      GdnHCl in the pre-transition zone have been measured. The data indicate that in
      1.5 M GdnHCl, IN is not fully populated on the US-->IS1-->IN-->N pathway because
      the rate of its formation is so slow that the US <--> UF <--> N pathway can
      effectively compete with that pathway. In 1.0 M GdnHCl, the US-->IS1-->IN
      transition is so fast that IN is fully populated. In 0.6 M GdnHCl, IN appears not
      to be fully populated because an alternative folding pathway, US-->IS2-->N,
      becomes available for the folding of US, in addition to the US-->IS1-->IN-->N
      pathway. Measurement of the binding of the hydrophobic dye 1-anilino-8
      naphthalenesulphonate (ANS) during folding indicates that ANS binds to two
      distinct intermediates, IM1 and IM2, that form within 2 ms on the US-->IM1-->IS1-
      >IN-->N and US-->IM2-->IS2-->N pathways. There is no evidence for the
      accumulation of intermediates that can bind ANS on the folding pathway of UF.

PMID- 7723035
TI  - Synthesis of simian virus 40 C-family catenated dimers in vivo in the presence of
      ICRF-193.
AB  - The effect of ICRF-193, a non-cleavable, complex-stabilizing type of
      topoisomerase II inhibitor, on SV40 DNA replication in vivo was examined. As
      analyzed by one and two-dimensional gel electrophoresis, C-family catenated
      dimers, each composed of two intertwined, covalently closed SV40 DNAs, were
      mainly synthesized in the presence of the drug. On removal of the drug these C
      family dimers were segregated into monomers. These results indicate that
      topoisomerase II is required for the segregation of replicated daughter
      molecules, but it is not absolutely required for the replication of DNA molecules
      up to the C-family dimers.

PMID- 7723036
TI  - DNA-binding surface of the Sso7d protein from Sulfolobus solfataricus.
AB  - We have used nuclear magnetic resonance (n.m.r.) spectroscopy to identify the DNA
      binding surface of the abundant, small and basic protein Sso7d from the
      hyperthermophilic archaebacterium Sulfolobus solfataricus. The Sso7d protein was
      previously found to bind strongly to double-stranded DNA sequences and to protect
      DNA from thermal denaturation, indicating that it might assume a similar function
      in vivo. Several amide resonances in two-dimensional n.m.r. 1H, 15N correlation
      spectra of 15N-enriched Sso7d are shifted and broadened upon addition of small
      amounts of ten base-pair or 19 base-pair duplex DNA oligomers under conditions
      where Sso7d-DNA complexes exchange rapidly on the n.m.r. time scale. The
      locations of the corresponding amides in the Sso7d structure define the surface
      that interacts with DNA. This surface coincides with a continuous region of
      strong positive electrostatic potential, which was calculated by means of
      numerical solution of the Poisson-Boltzmann equation. A model of the non-specific
      Sso7d-DNA complex is suggested based on the present data and previously obtained
      evidence that Sso7d interacts with the DNA major groove. The protein-DNA
      interface consists of a triple-stranded beta-sheet, which interacts with the DNA
      major groove and a reverse turn connecting the two strands of a double-stranded
      beta-sheet, which interacts with the minor groove. We note that the five (of 14)
      lysine side-chains that are specifically subjected to N zeta-monomethylation in
      the cell are located on surfaces of Sso7d that are exposed to the solvent in the
      proposed Sso7d-DNA complex.

PMID- 7723037
TI  - Triple-helix specific ligands stabilize H-DNA conformation.
AB  - Under superhelical stress, oligopurine-oligopyrimidine mirror-repeat sequences
      are able to adopt H-DNA conformations where a triple-helical and a single
      stranded structure co-exist. We have previously shown that a benzo[e]pyridoindole
      derivative (BePI), an antitumor drug interacting more tightly with triplex than
      with duplex DNA, strongly stabilizes intermolecular triple helices formed upon
      binding of homopyrimidine oligonucleotides to the major groove of double-stranded
      DNA at oligopurine-oligopyrimidine sequences. Here we show that an intramolecular
      triple helix is also strongly stabilized by this ligand. In vitro elongation
      performed by different DNA polymerases (bacteriophage T7, Escherichia coli or Taq
      polymerase) could be irreversibly inhibited by the H-DNA structure in the
      presence of BePI. A mirror-repeat polypurine-polypyrimidine sequence inserted
      between the E. coli beta-lactamase gene (conferring ampicillin resistance) and
      its bla promoter strongly inhibited transcription of the beta-lactamase gene in
      vivo. In the absence of supercoiling, transition to the H-conformation did not
      occur, but BePI stabilized the H-DNA structure induced by supercoiling as shown
      by chemical probes (chloroacetaldehyde). The results presented here open a new
      field of investigation for antitumor agents targeted to a novel class of genetic
      structures able to regulate gene expression.

PMID- 7723038
TI  - Probing the structure of a putative intermediate in homologous recombination: the
      third strand in the parallel DNA triplex is in contact with the major groove of
      the duplex.
AB  - A three-stranded DNA that is a putative intermediate of homologous recombination
      is a novel DNA triplex, R-form DNA. In R-form DNA the third strand includes both
      purines and pyrimidines and is parallel to the identical strand of the duplex. To
      test and refine our previously proposed R-form base triplets we have used two
      approaches: (1) dimethyl sulfate protection of R-form DNA; and (2) thermal
      dissociation of R-form DNAs in which the duplex strands were substituted in a
      strand-specific manner with either 7-deaza-guanine or 7-deaza-adenine. Together,
      the footprinting and isosteric substitution results demonstrate that the third
      strand in R-form DNA is in contact with the purines in the N7 position in the
      major groove of the Watson-Crick duplex in three ((GC):G, (AT):A and (TA):T) out
      of the four possible triplets. Furthermore, these results suggest that the N7
      positions of the duplex play a significant role in stabilizing the DNA-DNA
      contacts during the homology recognition process.

PMID- 7723039
TI  - Specific stimulation of recA-independent plasmid recombination by a DNA sequence
      at a distance.
AB  - Recombination between directly repeated DNA sequences can occur via both recA
      dependent and recA-independent mechanisms. They are differentially affected by
      the length of the repeat and the distance separating the repeats, respectively.
      Interestingly, a 623 base-pairs long DNA sequence of the plasmid pBR322 was found
      to stimulate specifically recA-independent recombination between tandem repeats.
      Analysis of this stimulating sequence has revealed the following features. (1).
      It is cis-acting. (2). No specific region of it appears to be essential for the
      effect. Moreover, a neutral sequence of comparable size was able to substitute
      for the sequence in influencing recombination. (3). The sequence affects
      recombination between tandem repeats within the tetA but not the bla gene of
      pBR322. (4). The sequence exerts its effect in a position-dependent manner. (5).
      It changes not only the frequency but also the products of recombination. Our
      results provide an example that recA-independent recombination can be influenced
      by DNA sequences at a distance.

PMID- 7723040
TI  - Secondary structure model for the last two domains of single-stranded RNA phage Q
      beta.
AB  - We have determined the nucleotide sequence of three positive single-stranded RNA
      coliphages and have used this information, together with the known sequences of
      the related phages Q beta and SP, to construct a secondary structure model for
      the two distal domains of Q beta RNA. The 3' terminal domain, which is about 100
      nucleotides long, contains most of the 3' untranslated region and folds into four
      short, regular hairpins. The adjacent 3' replicase domain contains about 1100
      nucleotides. Hairpins in this protein-coding domain are much longer and more
      irregular than in the 3' untranslated region. Both domains are defined by long
      distance interactions. The secondary structure is not a collection of hairpin
      structures connected by single-stranded regions. Rather, the RNA stretches
      between the stem-loop structures are all involved in an extensive array of long
      distance interactions that contract the molecule to a rigid structure in which
      all hairpins are predicted to have a fixed position with respect to each other. A
      general feature of the model is that helices tend to be organized in four-way
      junctions with little or no unpaired nucleotides between them. As a result, there
      is a potential for coaxial stacking of adjacent stems. The essential features of
      the model are supported by the S1 nuclease cleavage pattern. Viral RNA sequences
      are strongly constrained by their coding function. As a result, structural
      evolution by simple base-pair substitution is not always possible, as this
      usually requires the juxtaposition of the codon wobble positions in stems.
      Rather, we often observe co-ordinate base substitutions that maintain the stem,
      but tend to change the position at which bulges or internal loops are found.
      Structures that differ in this way are apparently equally fit. Also, the relative
      position of hairpin loops can shift several nucleotides through an alignment
      based on maximal sequence identity i.e. amino acid homology. The fact that these
      structural irregularities do not occur at the 3' untranslated region suggests
      indeed that the coding function of the RNA constrains the secondary structure.
      Hairpins with the stable tetraloop motif GNRA and UNCG or their complement are
      over-represented. This suggests their involvement in segregation of plus and
      minus strand. The genome of the coliphages contains a well-defined high affinity
      binding site for the coat protein, which serves to suppress replicase translation
      and also acts as a nucleation point in capsid formation. Close to the 3' end we
      find an additional conserved helix that meets the described consensus criteria
      for coat-protein binding.

PMID- 7723041
TI  - Translational positioning of nucleosomes on DNA: the role of sequence-dependent
      isotropic DNA bending stiffness.
AB  - A model has been derived that accounts for the nucleosome translational position
      in terms of the bending free energy that depends on the nearest-neighbor
      interactions between base-pairs. The available data on the nucleosome positioning
      on defined DNA sequences in the reconstituted systems have been analyzed. It has
      been shown that the model allows one to predict the preferred nucleosome
      translational positioning with an accuracy of about one turn of the double helix.
      The conclusion is made that the isotropic elastic properties of the DNA molecule
      are very important for nucleosome translational positioning. The anisotropic
      flexibility modulates the sequence-dependent preference and defines the precise
      rotational placement. The analysis points to a possible involvement of DNA
      bendability in nucleosome structural transitions. To model the nucleosome
      positioning within the chromatin fiber, the derived algorithm has been applied to
      random DNA sequences. The nucleosome distribution obtained is close to random,
      but nucleosomes, according to calculations, are placed on sites with a low value
      of bending free energy and decreased G+C-content. Relations with other work and
      some implications are discussed.

PMID- 7723042
TI  - Refined structure of cytochrome b562 from Escherichia coli at 1.4 A resolution.
AB  - The structure of cytochrome b562 from Escherichia coli has been refined at 1.4 A
      resolution against X-ray data collected on a Picker four-circle diffractometer.
      The triclinic unit cell parameters are a = 33.68 A, b = 50.48 A, c = 32.67 A,
      alpha = 102.51 degrees, beta = 86.56 degrees and gamma = 107.01 degrees and there
      are two molecules in the asymmetric unit. A total of 138 cycles of restrained
      crystallographic refinement using the program PROLSQ were augmented at
      intermediate stages by two cycles of simulated annealing refinement using X-PLOR.
      The final crystallographic R-factor is 16.4% for data in the resolution range 6.0
      A to 1.4 A for a model containing 1650 protein atoms, 86 heme atoms, 165 water
      molecules and four sulfate anions. The root-mean-square deviations from ideal
      bond lengths and angles are 0.012 A and 2.0 degrees, respectively. Each molecule
      consists of a bundle of four alpha-helices arranged in a simple up-down-up-down
      manner with a non-covalently bound heme group inserted between the first and
      fourth helices. In addition, there is a very short 3(10) helix in the 15-residue
      loop connecting the first and second pairs of helices. The two independent
      molecules show r.m.s. differences of 0.30 A for main-chain atoms and 0.88 A for
      all atoms. A detailed comparison with the structurally similar cytochrome c' from
      Rhodospirulum molishianum is presented. In addition, the titration behavior of
      cytochrome b562 in solution is discussed in terms of its molecular structure.

PMID- 7723043
TI  - The structure of an RNA pseudoknot that causes efficient frameshifting in mouse
      mammary tumor virus.
AB  - The structure of a 34-nucleotide RNA pseudoknot that causes efficient -1
      frameshifting in the messenger RNA of mouse mammary tumor virus has been
      investigated by NMR. Spectral assignment of the pseudoknot was facilitated by
      comparative NMR studies on the pseudoknot and on two smaller hairpin RNAs, and by
      using selective 13C labeling and 13C-edited NMR techniques. The three-dimensional
      structure of the pseudoknot has been determined. The frameshifter pseudoknot
      possesses structural features not observed in previously reported model
      pseudoknots. It has a compact structure with a pronounced bend at the junction of
      its G.C-rich stems. A single adenylate residue is intercalated between the two
      stems so that direct coaxial staking of the stems is not possible. The lack of an
      opposing nucleotide for the stacked, intervening adenylate creates a hinge in the
      pseudoknot. Most of the loop nucleotides are restrained by base staking
      interactions which keep the loops from adopting extended conformations. The
      sterically constrained loops direct the bending of the pseudoknot at the stem
      stem junction. The roles of the intercalated adenylate and loop lengths in
      causing bending can explain their requirement for efficient frameshifting. Our
      NMR data also indicate that there are internal dynamics associated with the
      pseudoknot. The unique, compact structure and conformational flexibility of the
      pseudoknot may be required for recognition and favourable interaction with the
      translating ribosome, or with translation factors associated with the ribosome.

PMID- 7723044
TI  - The solution structure of the F42A mutant of human interleukin 2.
AB  - Interleukin 2 (IL-2) is one of the major cytokines produced by T lymphocytes in
      response to antigen. It is a potent growth and differentiation factor for several
      cell-types and is structurally related to the four-helix bundle family of
      cytokines. Mutation of residue Phe42 to Ala abolishes binding to the alpha chain
      of the tri-partite IL-2 receptor. The three-dimensional structure of the F42A
      mutant IL-2 has been calculated by two dimensional NMR methods and compared to a
      structure of wild-type IL-2 determined by X-ray crystallography. The overall
      topology of the two structures is the same. The main differences between the
      structures are within the ill-defined loops connecting the helices and the region
      of the protein that is believed to interact with the alpha-chain of the receptor.
      Thus, the mutation of Phe42 to Ala does not perturb the overall three-dimensional
      structure of IL-2, and does not appear to change the putative binding sites for
      the beta and gamma chains of the receptor. The structural differences observed in
      this mutant suggest that the replacement of Phe42 with Ala causes the re
      orientation of neighbouring side-chains that are also involved in binding the
      alpha-chain of the receptor.

PMID- 7723045
TI  - Computer modeling of protein folding: conformational and energetic analysis of
      reduced and detailed protein models.
AB  - Recently we developed methods to generate low-resolution protein tertiary
      structures using a reduced model of the protein where secondary structure is
      specified and a simple potential based on a statistical analysis of the Protein
      Data Bank is employed. Here we present the results of an extensive analysis of a
      large number of detailed, all-atom structures generated from these reduced model
      structures. Following side-chain addition, minimization and simulated annealing
      simulations are carried out with a molecular mechanics potential including an
      approximate continuum solvent treatment. By combining reduced model simulations
      with molecular modeling calculations we generate energetically competitive,
      plausible misfolded structures which provide a more significant test of the
      potential function than current misfolded models based on superimposing the
      native sequence on the folded structures of completely different proteins. The
      various contributions to the total energy and their interdependence are analyzed
      in detail for many conformations of three proteins (myoglobin, the C-terminal
      fragment of the L7/L12 ribosomal protein, and the N-terminal domain of phage 434
      repressor). Our analysis indicates that the all-atom potential performs
      reasonably well in distinguishing the native structure. It also reveals
      inadequacies in the reduced model potential, which suggests how this potential
      can be improved to yield greater accuracy. Preliminary results with an improved
      potential are presented.

PMID- 7723046
TI  - Mechanical properties of the skin of Xenopus laevis (Anura, Amphibia).
AB  - The skin of the aquatic pipid frog, Xenopus laevis, was examined for specific
      biomechanical features: 1) thickness, 2) maximal strain at break (epsilon f), 3)
      tensile strength (sigma m), 4) modulus of elasticity (E, stiffness), and 5) the
      area under the stress-strain curve (W) (breaking energy, toughness). Skin freshly
      removed from dorsal, ventral, and lateral areas of the body was subjected to
      uniaxial tension. In both sexes, the dorsal skin is thicker than the ventral. The
      skin of male frogs was consistently thinner in all body regions than that of
      females. Most biomechanical parameters showed a considerable range of values in
      both males (epsilon f = 59-63%, sigma m = 15-16.5 MPa, E = 33.5-38.4 MPa, W = 3.8
      4.5 MJ/m3) and females (epsilon f = 102-126%, sigma m = 11.5 MPa, E = 10.4-12
      MPa, W = 5.2-6.7 MJ/m3). The disparate epsilon f values in males (low) and
      females (high) might reflect sexual dimorphism. Static stress-strain curves were
      typically J-shaped; with the exception of a "toe," the curves rose approximately
      linearly with increasing strain. The skin of X.laevis, although heterogeneous in
      structure, possesses features similar to those found in tissues with aligned
      collagen fibers such as tendons or fish skin. However, in anurans, the skin seems
      to play a more passive mechanical role during locomotion than in fish.

PMID- 7723047
TI  - Structure of the glomerular capillaries of the domestic chicken and desert quail.
AB  - The glomerular capillary architecture of nephrons that include a loop of Henle
      (looped) and those that lack the loop (loopless) nephrons was examined
      qualitatively and quantitatively by electron microscopy in Gallus gallus and
      Callipepla gambelii. The glomerular capillaries of looped nephrons form a
      dichotomously branched network, while those of loopless nephrons are arranged
      loosely, and the majority are unbranched. There was no significant difference in
      the diameter of the glomerular capillaries between looped and loopless nephrons;
      however, in all cases the diameter of the afferent arteriole was significantly
      larger than that of the efferent arteriole. Based on size alone, the predicted
      blood flow rate in the efferent arteriole is 20% that of the afferent arteriole
      in G.gallus and 7% that of the afferent arteriole in C.gambelii. There was no
      significant difference in the volume density (Vv) of the glomerular capillaries
      between looped and loopless nephrons. However, the surface area density (Sv) of
      the glomerular capillaries in loopless nephrons of C.gambelii was significantly
      larger than for the looped nephrons, and for the loopless nephrons in G. gallus.
      This suggests that there may be a decrease in blood flow rate along the
      glomerular capillaries of the loopless nephrons in C. gambelii. Overall, the
      results indicate that the avian glomerular capillaries are less complex than
      those of mammals.

PMID- 7723048
TI  - Superficial mandibular musculature and vocal sac structure in hemiphractine hylid
      frogs.
AB  - Three patterns of superficial mandibular musculature are described in
      hemiphractine hylid frogs. One of these is unique to the morphologically bizarre
      Hemiphractus. A second pattern is found in Flectonotus and also occurs in some
      species of Gastrotheca and Stefania. A third pattern involves a differentiated
      apical element of the m. intermandibularis and is found in Cryptobatrachus, many
      species of Gastrotheca, and one species of Stefania. Evidence supports the
      plesiomorphic state of an undifferentiated m. intermandibularis and two derived
      states of differentiation of that muscle. One of these is the development of
      supplementary posterolateral elements characteristic of the Phyllomedusinae,
      whereas the differentiation of an apical element has occurred in at least six
      independent lineages--the entire Pelodryadinae, three unrelated genera of
      Hylinae, and two genera of Hemiphractinae. Gastrotheca and Stefania are the only
      anuran genera known to include species possessing, and others lacking,
      differentiation of the m. intermandibularis. Vocal sacs and apertures are absent
      in Cryptobatrachus, Hemiphractus, Stefania, and six species of Gastrotheca.

PMID- 7723049
TI  - Mechanical properties of aponeurosis and tendon of the cat soleus muscle during
      whole-muscle isometric contractions.
AB  - Recent studies have suggested that the mechanical properties of aponeurosis are
      not similar to the properties of external tendon. In the present study, the
      lengths of aponeurosis, tendon, and muscle fascicles were recorded individually,
      using piezoelectric crystals attached to the surface of each structure during
      isometric contractions in the cat soleus muscle. We used a surgical microscope to
      observe the surface of the aponeurosis, which revealed a confounding effect on
      measures of aponeurosis length due to sliding of a thin layer of epimysium over
      the proximal aponeurosis. After correcting for this artifact, the stiffness
      computed for aponeurosis was similar to tendon, with both increasing from around
      8 F0/Lc (F0 is maximum isometric force and Lc is tissue length) at 0.1 F0 to 30
      F0/Lc at forces greater than 0.4 F0. At low force levels only (0.1 F0),
      aponeurotic stiffness increased somewhat as fascicle length increased. There was
      a gradient in the thickness of the aponeurosis along its length: its thickness
      was minimal at the proximal end and maximal at the distal end, where it converged
      to form the external tendon. This gradient in thickness appeared to match the
      gradient in tension transmitted along this structure. We conclude that the
      specific mechanical properties of aponeurosis are similar to those of tendon.

PMID- 7723050
TI  - Rabbit mitochondrial DNA diversity from prehistoric to modern times.
AB  - The mitochondrial genetic variability in European rabbit (Oryctolagus cuniculus)
      populations present in Europe and North Africa from 11,000 years ago to the
      present day has been analyzed using ancient DNA techniques. DNA was extracted
      from 90 rabbit bones found in 22 archaeological sites dated between the
      Mesolithic and recent times. Nucleotide sequences present in a variable 233-bp
      domain of the cytochrome b gene were compared to those present in modern-day
      rabbits. The results show that the structure of ancient populations of wild
      rabbit exhibited remarkable stability over time until the Middle Ages. At this
      time, a novel type of mtDNA molecule abruptly appears into most wild populations
      studied from France. This mtDNA type corresponds to that currently present in the
      domestic breeds of rabbit examined so far. The relative rapidity by which this
      mtDNA type established and its absence in all sites examined before 1,700 years
      ago lend support to the hypothesis that between 2,000 and 1,000 years ago, man
      may have favored the development, into all regions of France, of animals carrying
      this particular mtDNA molecule. The origin of such animals has still to be found:
      animals previously living outside of France or within France but in very
      restricted areas? This event was concomitant with the documented establishment of
      warrens after the tenth century A.D. in Europe.

PMID- 7723051
TI  - The expanding small heat-shock protein family, and structure predictions of the
      conserved "alpha-crystallin domain".
AB  - The ever-increasing number of proteins identified as belonging to the family of
      small heat-shock proteins (shsps) and alpha-crystallins enables us to reassess
      the phylogeny of this ubiquitous protein family. While the prokaryotic and fungal
      representatives are not properly resolved, most of the plant and animal shsps and
      related proteins are clearly grouped in distinct clades, reflecting a history of
      repeated gene duplications. The members of the shsp family are characterized by
      the presence of a conserved homologous "alpha-crystallin domain," which sometimes
      is present in duplicate. Predictions are made of secondary structure and solvent
      accessibility of this domain, which together with hydropathy profiles and intron
      positions support the presence of two similar hydrophobic beta-sheet-rich motifs,
      connected by a hydrophilic alpha-helical region. Together with an overview of the
      newly characterized members of the shsp family, these data help to define this
      family as being involved as stable structural proteins and as molecular
      chaperones during normal development and induced under pathological and stressful
      conditions.

PMID- 7723052
TI  - Recombination in AIDS viruses.
AB  - Recombination contributes to the generation of genetic diversity in human
      immunodeficiency viruses (HIV) but can only occur between viruses replicating
      within the same cell. Since individuals have not been found to be simultaneously
      coinfected with multiple divergent strains of HIV-1 or HIV-2, recombination
      events have been thought to be restricted to the rather closely related members
      of the quasispecies that evolves during the course of HIV infection. Here we
      describe examples of both HIV-1 and HIV-2 genomes that appear to be hybrids of
      genetically quite divergent viruses. Phylogenetic analyses were used to examine
      the evolutionary relationships among multiple HIV strains. Evolutionary trees
      derived from different genomic regions were consistent with respect to most of
      the viruses investigated. However, some strains of HIV-1 and HIV-2 exhibited
      significantly discordant branching orders indicative of genetic exchanges during
      their evolutionary histories. The crossover points of these putative
      recombination events were mapped by examining the distribution of
      phylogenetically informative sites supporting alternative tree topologies. A
      similar example of a recombinant simian immunodeficiency virus identified in West
      African green monkeys has also been described recently. These results indicate
      that coinfection with highly divergent viral strains can occur in HIV-infected
      humans and SIV-infected primates and could lead to the generation of hybrid
      genomes with significantly altered biological properties. Thus, future
      characterization of primate lentiviruses should include careful phylogenetic
      investigation of possible genomic mosaicism.

PMID- 7723053
TI  - Mammalian mitochondrial DNA evolution: a comparison of the cytochrome b and
      cytochrome c oxidase II genes.
AB  - The evolution of two mitochondrial genes, cytochrome b and cytochrome c oxidase
      subunit II, was examined in several eutherian mammal orders, with special
      emphasis on the orders Artiodactyla and Rodentia. When analyzed using both
      maximum parsimony, with either equal or unequal character weighting, and neighbor
      joining, neither gene performed with a high degree of consistency in terms of the
      phylogenetic hypotheses supported. The phylogenetic inconsistencies observed for
      both these genes may be the result of several factors including differences in
      the rate of nucleotide substitution among particular lineages (especially between
      orders), base composition bias, transition/transversion bias, differences in
      codon usage, and different constraints and levels of homoplasy associated with
      first, second, and third codon positions. We discuss the implications of these
      findings for the molecular systematics of mammals, especially as they relate to
      recent hypotheses concerning the polyphyly of the order Rodentia, relationships
      among the Artiodactyla, and various interordinal relationships.

PMID- 7723054
TI  - Molecular classification of living organisms.
AB  - Recent studies in molecular evolution have generated strong conflicts in opinion
      as to how world living organisms should be classified. The traditional
      classification of life into five kingdom has been challenged by the molecular
      analysis carried out mostly on rRNA sequences, which supported the division of
      the extant living organisms into three major groups: Archaebacteria, Eubacteria,
      and Eukaryota. As to the problem of placing the root of the tree of life, the
      analysis carried out on a few genes has provided discrepant results. In order to
      measure the genetic distances between species, we have carried out an
      evolutionary analysis of the glutamine synthetase genes, which previously have
      been revealed to be good molecular clocks, and of the small and large rRNA genes.
      All data demonstrate that archaebacteria are more closely related to eubacteria
      than to eukaryota, thus supporting the classical division of living organisms
      into two main superkingdoms, Prokaryota and Eukaryota.

PMID- 7723055
TI  - Nonrandom frequency patterns of synonymous substitutions in homologous mammalian
      genes.
AB  - All 69 homologous coding sequences that are currently available in four mammalian
      orders were aligned and the synonymous positions of quartet and duet (fourfold
      and twofold degenerate) codons were divided into three classes (that will be
      called conserved, intermediate, and variable) according to whether they show no
      change, one change, or more than one change, respectively. We observed (1) that
      the frequencies of conserved, intermediate, and variable positions of quartet and
      duet codons are different in different genes; (2) that the frequencies of the
      three classes are significantly different from expectations based on a random
      substitution process in the majority of genes (especially for GC-rich genes) for
      quartet codons and in a minority of genes for doublet codons; and (3) that the
      frequencies of the three classes of positions of quartet codons are correlated
      with those of duet codons, the conserved positions of quartet and duet codons
      being, in addition, correlated with the degree of amino acid conservation. Our
      main conclusions are that synonymous substitution frequencies: (1) are gene
      specific; (2) are not simply the result of a stochastic process in which
      nucleotide substitutions accumulate at random, over time; and (3) are correlated
      in quartet and duet codons.

PMID- 7723056
TI  - Specific compositional patterns of synonymous positions in homologous mammalian
      genes.
AB  - All 69 homologous coding sequences that are currently available in four mammalian
      orders were aligned and the synonymous (ie., third) positions of quartet
      (fourfold degenerate) codons were divided into three classes (that will be called
      conserved, intermediate, and variable), according to whether they show no change,
      one change, and more than one change, respectively. The three classes were
      analyzed in their compositional patterns. In the majority of GC-rich genes, the
      three classes of positions (but especially conserved positions) exhibited
      significantly different base compositions compared to expectations based on a
      "random" substitution process from the "ancestral" (consensus) sequence to the
      present-day (actual) sequences. Significant differences were rare in GC-poor
      genes. An analysis of the present results indicates that natural selection plays
      a role in the synonymous nucleotide substitution process, especially in GC-rich
      genes which represent the vast majority of mammalian genes.

PMID- 7723057
TI  - Statistical analysis of vertebrate sequences reveals that long genes are scarce
      in GC-rich isochores.
AB  - We compared the exon/intron organization of vertebrate genes belonging to
      different isochore classes, as predicted by their GC content at third codon
      position. Two main features have emerged from the analysis of sequences published
      in GenBank: (1) genes coding for long proteins (i.e., > or = 500 aa) are almost
      two times more frequent in GC-poor than in GC-rich isochores; (2) intervening
      sequences (= sum of introns) are on average three times longer in GC-poor than in
      GC-rich isochores. These patterns are observed among human, mouse, rat, cow, and
      even chicken genes and are therefore likely to be common to all warm-blooded
      vertebrates. Analysis of Xenopus sequences suggests that the same patterns exist
      in cold-blooded vertebrates. It could be argued that such results do not reflect
      the reality because sequence databases are not representative of entire genomes.
      However, analysis of biases in GenBank revealed that the observed discrepancies
      between GC-rich and GC-poor isochores are not artifactual, and are probably
      largely underestimated. We investigated the distribution of microsatellites and
      interspersed repeats in introns of human and mouse genes from different
      isochores. This analysis confirmed previous studies showing that L1 repeats are
      almost absent from GC-rich isochores. Microsatellites and SINES (Alu, B1, B2) are
      found at roughly equal frequencies in introns from all isochore classes.
      Globally, the presence of repeated sequences does not account for the increased
      intron length in GC-poor isochores. The relationships between gene structure and
      global genome organization and evolution are discussed.

PMID- 7723058
TI  - Intrastrand parity rules of DNA base composition and usage biases of synonymous
      codons.
AB  - When there are no biases in mutation and selection between the two strands of
      DNA, the 12 possible substitution rates of the four nucleotides reduces to six
      (type 1 parity rule or PR1), and the intrastrand average base composition is
      expected to be A = T and G = C at equilibrium without regard to the G + C content
      of DNA (type 2 parity rule or PR2). Significant deviations from the parity rules
      in the third codon letters of the four-codon amino acids result mostly from
      selective biases rather than mutational biases between the two strands of DNA
      during evolution. The parity rules lay the foundation for evaluating the biases
      in synonymous codon usage in terms of (1) directional mutation pressure for
      variation of the DNA G + C content due to mutational biases between alpha-bases
      (A or T) and gamma-bases (G or C), (2) strand-bias mutation, for example, by DNA
      repair during transcription, and (3) functional selection in evolution, for
      example, due to tRNA abundance. The present analysis shows that, although the PR2
      violation is common in the third codon letters of four-codon amino acids, the
      contribution of PR2 violation to the DNA G + C content of the third codon
      position is small and, in majority of cases, mildly counteracts the effect of the
      directional mutation pressure on the G + C content.

PMID- 7723059
TI  - Properties of a general model of DNA evolution under no-strand-bias conditions.
AB  - Under the hypothesis of no-strand-bias conditions, the Watson and Crick base
      pairing rule decreases the complexity of models of DNA evolution by reducing to
      six the maximum number of substitution rates. It was shown that intrastrand
      equimolarity between A and T (A*=T*) and between G and C (G*=C*) [corrected] is a
      general asymptotic property of this class of models. This statistical prediction
      was observed on 60 long genomic fragments (> 50 kbp) from various kingdoms, even
      when the effect of the two opposite orientations for coding sequences is removed.
      The practical consequence of the model for estimating the expected number of
      substitutions per site between two homologous DNA sequences is discussed.

PMID- 7723060
TI  - Different evolutionary histories of kringle and protease domains in serine
      proteases: a typical example of domain evolution.
AB  - With the aim of elucidating the evolutionary processes of the kringle and
      protease domains in serine proteases which are involved with the system of blood
      coagulation and fibrinolysis, we constructed phylogenetic trees for the kringle
      and protease domains, separately, by use of amino acid sequence data. The
      phylogenetic trees constructed clearly showed that the topologies were different
      between the kringle and protease domains. Because both domains are coded by
      single peptides of serine proteases, this strongly suggests that the kringle and
      protease domains must have undergone different evolutionary processes. Thus,
      these observations imply that serine proteases evolve in a way such that each
      domain is a unit of evolution, exemplifying a typical mode of domain evolution. A
      possible relationship between the domain evolution and the exon shuffling theory
      is also discussed from the viewpoint of gene evolution.

PMID- 7723061
TI  - Segmented structure of protein sequences and early evolution of genome by
      combinatorial fusion of DNA elements.
AB  - A theory of an early stage of genome evolution by combinatorial fusion of
      circular DNA units is suggested, based on protein sequence "fossil" evidence. The
      evidence includes preference of protein sequence lengths for certain sizes-
      multiples of 123 aa for eukaryotes and multiples of 152 aa for prokaryotes. At
      the DNA level these sizes correspond to 350-450 base pairs--the known optimal
      range for DNA ring closure. The methionine residues repeatedly appear along the
      sequences with the same period of about 120 aa (in eukaryotes), presumably
      marking the sites of insertion of the early genes--rings of protein-coding DNA.
      No torsional constraint in this DNA results in very sharp estimate of the helical
      periodicity of the early DNA, indistinguishable from the experimental mean value
      for extant DNA. According to the combinatorial fusion theory, based on the above
      evidence, in the pregenomic, prerecombinational stage the genes and the noncoding
      sequences existed in form of autonomously replicating DNA rings of close to
      standard size, randomly segregating between dividing cells, like modern plasmids
      do. In the recombinational early genomic stage the rings started to fuse, forming
      larger DNA molecules consisting of several unit genes connected in various
      combinations and forming long protein-coding sequences (combinatorial fusion).
      This process, which involved, perhaps, noncoding sequences as well, eventually
      resulted in the formation of large genomes. The dispersed circular DNA--or,
      rather, evolutionarily advanced derivatives thereof--may still exist in the form
      of various mobile DNA elements.

PMID- 7723062
TI  - Compositional correlations in the nuclear genes of the flatworm Schistosoma
      mansoni.
AB  - We have investigated the genome organization in the flatworm Schistosoma mansoni.
      First, we analyzed the compositional distributions of the three codon positions.
      Second, we investigated the correlations that exist between (1) the GC levels of
      exons against flanking regions, (2) the GC levels of third codon positions
      against flanking regions, (3) the dinucleotide frequencies of exons against
      flanking regions, and (4) the GC levels of 5' against 3' regions. The modality of
      the distribution of third codon positions, together with the significant
      correlations found, leads us to propose that the nuclear genome of this species
      is compositionally compartmentalized.

PMID- 7723063
TI  - Widespread metabolic depression and reduced somatosensory circuit activation
      following traumatic brain injury in rats.
AB  - The effects of fluid percussion brain injury on the basal metabolic state and
      responsiveness of a somatosensory circuit to physiologic activation were
      investigated with [14C]2-deoxyglucose autoradiography. Under controlled
      physiologic conditions and normothermic brain temperature (37 degrees C), rats
      were injured with a moderate fluid percussion pulse ranging from 1.7 to 2.1 atm.
      At 4 or 24 h after traumatic brain injury (TBI), unilateral vibrissae stimulation
      was carried out, resulting in the metabolic activation of the whisker-barrel
      circuit. In sham-operated control animals, whisker stimulation resulted in the
      metabolic activation of the ipsilateral trigeminal medullary complex (177% of
      control), contralateral ventrobasal thalamus (143% control), and primary
      somatosensory cortex (153% control). At 4 h after injury, local cerebral
      metabolic rates of glucose (ICMRglu) were significantly depressed throughout the
      traumatized hemisphere. Although depressed ICMRglu was most pronounced in
      cortical regions adjacent to the evolving contusion (53% of control), significant
      decreases were also seen in more remote areas, including the frontal cortex (75%
      of control), hippocampus (79% control), and lateral thalamus (68% of control). At
      24 h following TBI, ICMRglu remained significantly reduced at the impact site,
      within the ipsilateral somatosensory cortex and lateral thalamus. Stimulus-evoked
      increases in ICMRglu were depressed within all three relay stations of the
      vibrissae-barrel-field circuit at 4 and 24 h after TBI. These results demonstrate
      both focal and diffuse metabolic depression after moderate TBI. Although the most
      severe and longer lasting metabolic consequences occurred in cortical and
      thalamic regions destined to exhibit histopathologic damage, milder
      abnormalities, most prominent in the early posttraumatic period, were also seen
      in noninjured areas. The inability to activate the somatosensory circuit
      metabolically indicates that circuit dysfunction is an acute consequence of TBI.
      Widespread circuit or synaptic dysfunction would be expected to participate in
      the functional and behavioral consequences of TBI.

PMID- 7723064
TI  - Combined fluid percussion brain injury and entorhinal cortical lesion: a model
      for assessing the interaction between neuroexcitation and deafferentation.
AB  - Laboratory studies suggest that excessive neuroexcitation and deafferentation
      contribute to long-term morbidity following human head injury. Because no current
      animal model of traumatic brain injury (TBI) has been shown to combine excessive
      neuroexcitation and significant levels of deafferentation, we developed a rat
      model combining the neuroexcitation of fluid percussion TBI with subsequent
      entorhinal cortical (EC) deafferentation. In this paradigm, moderate fluid
      percussion TBI was induced in each rat, followed 24 h later by bilateral EC
      lesion (BEC). Six conditions were examined: (1) fluid percussion TBI followed 24
      h later by bilateral EC lesion (TBEC), (2) fluid percussion TBI (TBI), (3)
      bilateral EC lesion (BEC), (4) sham fluid percussion TBI (SHAM), (5) TBI followed
      24 h later by unilateral EC lesion (TUEC), and (6) unilateral EC lesion (UEC).
      The first four groups were assessed for motor (with beam-balance and beam-walk
      testing) and cognitive deficits (with the Morris water maze) and hippocampal
      morphology (with immunocytochemistry and electron microscopy). The TUEC and UEC
      groups were assessed for cognitive deficits alone. Motor deficits were greater in
      the TBEC injury than in TBI or sham alone; however, no significant difference was
      observed between the TBEC and BEC conditions in motor performance. Cognitive
      deficits were of a greater magnitude in the combined TBEC injury model relative
      to each individual insult. These cognitive deficits appeared to be additive for
      the two experimental injuries, BEC deafferentation producing deficits
      intermediate between TBI and TBEC insults. Morphologic analysis of the dentate
      gyrus molecular layer at 15 days after TBEC showed that the distribution of
      synaptophysin-positive presynaptic terminals was distinct from that observed
      after either TBI or BEC alone. Specifically, the laminar pattern of presynaptic
      rearrangement induced by BEC lesion did not occur after TBEC injury. The present
      results show that axonal injury and its attendant deafferentation, when coupled
      with traumatically induced neuroexcitation, produce an enhancement of the
      morbidity associated with TBI. Moreover, they indicate that this model can
      effectively be used to study the interaction between neuroexcitation and synaptic
      plasticity.

PMID- 7723065
TI  - Histopathologic consequences of moderate concussion in an animal model:
      correlations with duration of unconsciousness.
AB  - Although duration of unconsciousness is commonly used as a prognostic index
      following traumatic brain injury (TBI), few controlled studies have statistically
      evaluated the relationship between unconsciousness and histologic pathology,
      particularly after moderate head injury. Using a pendulum-striker concussive
      device, a reproducible model of TBI in rats was developed. This model is
      uncomplicated by skull fractures, contusions, or experimenter-induced
      craniotomies. In the present study, the severity of the histopathology observed
      in this model of moderate closed-head injury at 48 h posttrauma is linearly
      related to the duration of unconsciousness (p < 0.0001). The pathology, assessed
      with a silver stain for neurodegeneration, is particularly striking if
      unconsciousness persists for 4 minutes or more. These data suggest that the
      initial period of unconsciousness may be a useful predictor of clinical brain
      histopathology associated with moderate closed-head injury, predicting either the
      degree of pathology and/or the rate it progresses if left untreated.

PMID- 7723066
TI  - Acute subdural hematoma: is the blood itself toxic?
AB  - Recently developed rodent models of acute subdural hematoma have shown an
      associated large area of infarction underlying the clot. Excitotoxic processes
      have been postulated to play an important role in the extensive cell death seen
      with these models. However, whether increased pressure, vasoactive effects, or
      toxicity of the blood itself is responsible for initiating or sustaining these
      processes remains unclear. To study the effect of blood itself, an opaque layer
      of autologous clot was placed on the widely exposed parietal cortex of 15 Long
      Evans rats and left in place for 72 h. In control animals the cortical surface
      was exposed but no blood was placed and contact with blood products was carefully
      limited. These animals were compared to a group in whom blood was injected into
      the closed subdural space. Histologic analysis showed that the majority of the
      cortex in both control and experimental animals in the open cranial model group
      appeared normal. Scattered small, discrete hemorrhagic lesions on the cortical
      surface of both control and experimental animals were seen, which had the
      appearance of focal mechanical trauma or vessel avulsion. There was no
      significant difference in average volume of lesions between experimental and
      control animals (9.1 versus 9.7 mm3, p = 0.85). No areas of infarction or
      selective neuronal loss were seen. In comparison, animals in which blood was
      injected into the subdural space had significantly larger lesions underlying
      clot, averaging 133.6 mm3 in volume (p < 0.0003). Blood in prolonged contact with
      the cortical surface in the absence of increased pressure, ischemia, or other
      insult is insufficient to cause underlying infarction like that seen when a
      similar volume of blood is injected into the closed subdural space.

PMID- 7723067
TI  - Treatment of vasogenic brain edema with the novel Cl- transport inhibitor
      torasemide.
AB  - The efficacy of the diuretic agent torasemide, which antagonizes the Na+/K+/Cl-
      cotransport and Cl- channels, was investigated to determine its inhibition of
      brain edema from a focal cerebral lesion. For this purpose, cold injury of the
      brain was induced in 50 Sprague-Dawley rats while monitoring arterial blood
      pressure. The brain was removed for gravimetric assessment of swelling of the
      traumatized hemisphere 24 h after trauma. The water content was also determined
      after drying the cerebral hemispheres for 24 h. Animals were divided into five
      groups. A control group with trauma received vehicle only; two other groups
      received 1.0 or 10.0 mg torasemide/kg body weight 30 minutes before and 6 h after
      trauma (n = 10-12). Administration of the drug after the insult was also
      investigated in animals with application of vehicle or 10.0 mg/kg of torasemide
      at 30 minutes and 6 h following the brain lesion (n = 8). Torasemide did not
      affect important physiologic variables, such as the arterial pO2, pCO2, pH,
      hemoglobin, hematocrit, or plasma osmolality, while increasing blood pressure (p
      < 0.01). The blood pressure response notwithstanding, treatment significantly
      attenuated hemispheric brain swelling from trauma. In control animals without
      treatment, cold injury led to hemispheric swelling of 8.89%. In animals with 1 mg
      torasemide/kg BW, brain swelling amounted to 8.51% and to 7.04% in animals
      receiving 10 mg/kg before and after the insult (p < 0.005). Treatment was also
      found to attenuate the increase in tissue water content from trauma, but without
      reaching statistical significance. Postinsult treatment with torasemide (10 mg/kg
      BW) at 30 minutes and 6 h after trauma was again associated with a significant
      reduction in hemispheric brain swelling, which in this group amounted to 7.46%
      compared with 9.76% in the untreated controls (p < 0.005). The increase in the
      cerebral water content from trauma was also significantly blunted in the latter
      experiments (p < 0.01). The present data indicate a remarkable therapeutic
      potential of the novel diuretic agent torasemide to reduce vasogenic brain edema
      from an acute cerebral lesion. It is surmised that the compound specifically
      interferes with Cl- transport mechanisms, which apparently are activated in
      edematous brain involving neuronal and glial cells, for example. This conclusion
      is supported by in vitro observations that torasemide inhibits the swelling of
      glial cells from acidosis. On the other hand, it is unlikely that gross
      dehydration of the brain secondary to the induction of diuresis by the agent
      played a role, because hematocrit and plasma osmolality were not found to be
      affected.

PMID- 7723068
TI  - Effect of remacemide hydrochloride on subarachnoid hemorrhage-induced vasospasm
      in rabbits.
AB  - The purpose of this study was to assess the role of an excitatory amino acid
      (EAA) receptor antagonist (remacemide hydrochloride) in a rabbit model of
      subarachnoid hemorrhage (SAH)-induced cerebral vasospasm. Cerebral angiograms
      were performed on 22 rabbits pre-SAH and 72 h post-SAH: 6 rabbits received an
      injection of mock cerebrospinal fluid (1 ml/kg) into the cisterna magna (group I,
      the control group); 6 rabbits were subjected to SAH but received no treatment
      (group II); autologous blood (1 ml/kg) from the central ear artery was injected
      into the cisterna magna of these rabbits; 6 rabbits were subjected to SAH (1
      ml/kg) and treated with intraperitoneal (IP) bolus injections of remacemide
      hydrochloride (15 mg/kg) every 12 h beginning 30 minutes after SAH (group III);
      and 4 rabbits were not subjected to SAH but received IP bolus injections of
      remacemide hydrochloride every 12 h (group IV). Digital subtraction angiography
      was used to measure the diameter of the basilar artery. At 72 h post-SAH,
      vasospasm was evident in all untreated rabbits. The diameter of the basilar
      artery was reduced significantly below pre-SAH levels by 35.3 +/- 5.8% (mean +/-
      standard error of the mean). Treatment with remacemide hydrochloride
      significantly ameliorated vasospasm (27.3 +/- 5.4%, p < 0.001). These findings
      suggest that in this model EAAs may cooperate in the genesis of SAH-induced
      cerebral vasospasm and that NMDA receptor antagonism with remacemide
      hydrochloride can partially prevent the SAH-induced vasospasm of a large cerebral
      artery.

PMID- 7723069
TI  - Electrical field distribution within the injured cat spinal cord: injury
      potentials and field distribution.
AB  - This study investigated the spontaneous injury potentials measured after
      contusion or transection injury to the cat spinal cord. In addition, the
      distribution of electrical field potentials on the surface and within the spinal
      cord were measured following applied electrical fields after transection and
      contusion injuries. After transection of the spinal cord, the injury potentials
      were -19.8 +/- 2.6 mV; after contusion of the spinal cord, the injury potentials
      were -9.5 +/- 2.2 mV. These potentials returned to control values within 2.5-4h
      after injury. The electrical field distribution measured on the dorsal surface,
      as well as within the spinal cord, after the application of a 10 microA current,
      showed little difference between contusion and transection injuries. Scalar
      potential fields were measured using two configurations of stimulating
      electrodes: dorsal to dorsal (D-D), in which both electrodes were placed
      epidurally on the dorsal surface of the spinal cord, and ventral to dorsal (V-D),
      in which one electrode was placed dorsally and one ventrally. As reported in
      normal uninjured cats, the total current in the midsagittal plane for the D-D
      configuration was largely confined to the dorsal portion of the spinal cord; with
      the V-D configuration, the current distribution was uniform throughout the spinal
      cord. In the injured spinal cord, the equipotential lines midway between the
      stimulating electrodes have a wider separation than in the uninjured spinal cord.
      Because the magnitude of the electrical field E is equal to the current density J
      multiplied by the resistivity r, this suggests that either the current density is
      reduced or that the resistivity is reduced.

PMID- 7723071
TI  - Workshop on animal models of traumatic brain injury.

PMID- 7723070
TI  - Reduced transverse spinal area secondary to burst fractures: is there a
      relationship to neurologic injury?
AB  - A retrospective case-control study was undertaken to determine the best technique
      to measure neural canal encroachment at each lumbar level following burst
      fracture and its relationship to the presence of neurologic deficit. Only
      patients with postinjury CT scans demonstrating a disrupted posterior body with a
      retropulsed bone fragment were included. Patients were divided into groups based
      on the level of bony injury (T12-L5) and neurologic status. Neurologic injury was
      classified as follows: normal (N), root (R), or cauda
      equina/conus/paraplegic/paraparetic (C/P). The mean transverse spinal area (TSA,
      cm2), spinal canal percentage patency (PP), and midsagittal diameter (MSD) were
      determined for each neurologic group and lumbar level. A "calculated" TSA, based
      on midsagittal and anterior-posterior diameters, was also derived for each
      patient. The data were compared level by level and correlated with the patient's
      neurologic status. At L1, the critical TSA was 1.0 cm2. All patients with TSAs
      less than this were paraplegic. At both T12 and L1, TSAs in the range of 1.0-1.25
      cm2 were observed in both normal and neurologically impaired patients. A
      critically significant TSA was not established for levels T12, L2, L3, L4, or L5;
      however, the data indicated that a smaller TSA can be tolerated at successively
      caudal levels without neurologic deficit. No meaningful correlation between root
      injury and TSA was observed. The data also indicated that measurement of TSA is a
      more accurate method for evaluating neural canal encroachment than PP or MSD. The
      "calculated" TSA is a simple, objective method for obtaining this information
      without the aid of a computer. This study suggests that absolute TSA should be
      utilized in future studies evaluating decompressive treatment of thoracolumbar
      pathology.

PMID- 7723072
TI  - Accumulation and handling of inorganic mercury in the kidney after
      coadministration with glutathione.
AB  - The accumulation and handling of mercury in the blood, kidneys, and liver were
      evaluated and compared in rats 5 min, 1 h, and 24 h after the intravenous
      administration of either a 0.25 mumol/kg dose of inorganic mercury or a 0.25
      mumol/kg dose of inorganic mercury plus a 0.5 mumol/kg dose of glutathione (GSH)
      to determine the possible role of extracellular GSH and complexes of GSH and
      inorganic mercury in the renal uptake and transport of inorganic mercury.
      Significantly more of the injected dose of inorganic mercury was present in the
      blood of the rats injected with inorganic mercury alone than in the blood of the
      rats injected simultaneously with both inorganic mercury and GSH at all times
      evaluated after injection. Of the mercury remaining in the blood, however,
      significantly more mercury was in plasma fraction of blood in the rats injected
      with both inorganic mercury and GSH than in the plasma fraction of blood in the
      rats injected with inorganic mercury alone. The blood and plasma findings
      indicate that much of the mercury injected with GSH was in some complex that
      allowed the mercury to be cleared from the blood more readily and prevented the
      mercury from entering readily into red blood cells. The renal concentration of
      mercury was significantly greater in the rats injected with both inorganic
      mercury and GSH than in the rats injected with inorganic mercury alone at 5 min
      and 1 h, but not 24 h, after injection. This increased renal accumulation of
      mercury during the initial hours after injection was due mainly to enhanced
      uptake and/or retention of mercury in the renal cortex. Urinary excretion of
      mercury, over 24 h, was also slightly, but significantly, greater in the rats
      injected with both inorganic mercury and GSH simultaneously. These data indicate
      that coadministration of a nontoxic dose of inorganic mercury with a twofold
      higher amount (in moles) of GSH increases significantly the clearance of mercury
      from the blood and increases the renal cortical accumulation of inorganic mercury
      during the initial 1 h after injection. Moreover, the data in this study are
      consistent with the hypothesis that extracellular GSH is an important ligand to
      which mercuric ions bind, and that complexes of inorganic mercury and GSH in the
      blood and/or ultrafiltrate probably play a role in the renal uptake of some of
      the mercury in blood after exposure to mercuric compounds.

PMID- 7723074
TI  - Erythrocyte-aniline interaction leads to their accumulation and iron deposition
      in rat spleen.
AB  - In order to understand the splenic toxicity of aniline in rats, early interaction
      of aniline with erythrocytes and its subsequent deposition and covalent binding
      to macromolecules in target (spleen) and nontarget (liver) organs have been
      studied. Male Sprague-Dawley (SD) rats were given 1 or 3 doses of 1 mmol/kg
      [14C]aniline hydrochloride (1 dose/d) by gavage and euthanized 24 h after the
      treatment. Among blood components, maximum radioactivity was found to be
      associated with red blood cells (RBCs). After 3 doses, there was 112, 79, and 67%
      increase in the radioactivity in the whole blood, RBCs, and hemolysate,
      respectively, in comparison to 1 dose. In comparison to RBCs, plasma had only 40
      and 16% radioactivity after the administration of 1 and 3 doses, respectively.
      Spleen homogenate at 1 dose had one-third of the radioactivity in the TCA
      precipitate, which increased to 40% at 3 doses, while the total radioactivity
      increased 256% over 1 dose. Liver, which had almost double the radioactivity on a
      per gram tissue basis compared to the spleen at one dose, did not show any
      appreciable increase in the radioactivity at three doses. However, radioactivity
      in the TCA precipitate of liver homogenate increased by 92% after 3 doses. The
      iron content of the spleen in rats given 3 doses of [14C]aniline increased by 85%
      compared to the rats given just 1 dose. The iron content of liver did not show
      any change at three doses. These data thus demonstrate a dose-dependent binding
      and accumulation of radioactivity in erythrocytes and spleen. These interactions,
      along with parallel increases in the iron content of the spleen, could be
      critical in the splenic toxicity of anilines.

PMID- 7723073
TI  - Renal disposition of mercury in rats after intravenous injection of inorganic
      mercury and cysteine.
AB  - The disposition of mercury in the blood, kidneys and liver was evaluated and
      compared in rats 5 min, 1 h, and 24 h after the intravenous administration of a
      0.25 mumol/kg dose of inorganic mercury or a 0.25 mumol/kg dose of inorganic
      mercury plus a 0.5 mumol/kg dose of cysteine to determine the possible role of
      extracellular cysteine and complexes of cysteine and inorganic mercury in the
      renal uptake and transport of inorganic mercury. More inorganic mercury was
      present in the blood of the rats injected with inorganic mercury alone than in
      the blood of the rats injected simultaneously with both the inorganic mercury and
      cysteine during the first hour after injection. In addition, significantly more
      mercury was in the plasma fraction of blood in the rats injected with both
      inorganic mercury and cysteine than in the rats injected with inorganic mercury
      alone. These findings indicate that much of the mercury injected with cysteine
      was in some form of a complex that allowed the mercury to be cleared from the
      blood more readily and prevented the mercury from entering readily into the
      cellular components of blood. The renal concentration of mercury was
      significantly greater in the rats injected with both inorganic mercury and
      cysteine than in the rats injected with inorganic mercury alone 1 h, but not 24
      h, after injection. This increased renal accumulation of mercury during the
      initial hour after injection was due mainly to enhanced uptake and/or retention
      of mercury in the renal cortex, although some of the enhanced accumulation of
      mercury also occurred in the outer stripe of the outer medulla during the first
      hour after injection. These data indicate that coadministration of a nontoxic
      dose of inorganic mercury with a twofold higher amount (in moles) of cysteine
      increases significantly the clearance of mercury from the blood and increases the
      accumulation of inorganic mercury in the renal cortex and outer stripe of the
      outer medulla during the initial 1 h after injection. In conclusion, the data in
      this study are consistent with the hypothesis that complexes of inorganic mercury
      and cysteine in the blood and/or ultrafiltrate probably play a role in the renal
      uptake of some of the mercury in blood after exposure to mercuric compounds.

PMID- 7723075
TI  - Differential effects of dietary diallyl sulfide and diallyl disulfide on rat
      intestinal and hepatic drug-metabolizing enzymes.
AB  - The chemopreventive properties of allyl sulfides on carcinogenesis may be related
      to the modulation of drug-metabolizing enzymes involved in carcinogen activation
      or detoxication. In order to investigate the effects of diallyl sulfide (DAS) and
      diallyl disulfide (DADS) on intestinal and hepatic drug-metabolizing enzymes,
      rats were fed a diet containing 0.2% of either allyl sulfide. The DADS enhanced
      intestinal epoxide hydrolase (EH) and cytochrome P-450 (P-450) 2B1/2 protein
      levels and the activities of pentoxy- and benzyl-oxyresorufin O-dealkylases,
      arylhydrocarbon hydroxylase, microsomal epoxide hydrolase, p-nitrophenol UDP
      glucuronyl transferase and glutathione S-transferase, and decreased
      nitrosodimethylamine demethylase activity. In liver, DADS produced similar
      effects and, in addition, increased P-450 1A1/2 protein level and phenoxazone
      metabolizing activities (ethoxy- and methoxyresorufin O-dealkylases), p
      hydroxybiphenyl UDP-glucuronyl transferase, and decreased P-450 2E1 level. The
      DAS enhanced only EH activity in the small intestine and induced P-450 2B1/2 and
      epoxide hydrolase protein levels. In liver, DAS produced similar effects as DADS.
      The different effects of DAS on intestinal drug-metabolizing enzymes, compared to
      liver, could be ascribed to less metabolism of this compound in small intestine.
      It is also suggested that DAS and DADS may not yield the same metabolites and
      therefore would have different effects on intestinal drug-metabolizing enzymes.

PMID- 7723076
TI  - Factors affecting species differences in the kinetics of metabolites of
      trichloroethylene.
AB  - The hepatocarcinogenicity of trichloroethylene (TRI) in mice has been attributed
      to a metabolite, trichloroacetate (TCA). Rats of various strains appear to be
      resistant to TRI-induced hepatocarcinogenesis and produce lower peak
      concentrations of TCA. Mice, however, also form significant amounts of another
      carcinogenic metabolite, dichloroacetate (DCA). The present study was conducted
      to investigate the interspecies differences in the metabolism of TRI between the
      mouse, rat, and dog and to gain further insight into the role metabolic factors
      may play in the apparent species specificity of liver tumor induction by TRI.
      Fischer 344 rats and beagle dogs were dosed orally with TRI and blood was
      analyzed for TRI, DCA, TCA, and trichloroethanol (TCE). Data on the metabolism of
      TRI in mice have been previously published. Limited data are available on the
      metabolism of TRI in humans. Dogs produce higher peak concentrations and have a
      larger area under the concentration-time curve (AUC) for TCA as compared to rats
      given similar doses of TRI. Dichloroacetate was not found in measurable
      concentrations, that is, above 4 nmol/ml, the minimal quantifiable concentration,
      in the blood of either rats or dogs. Appreciable concentrations of DCA were found
      in the blood of mice administered TRI in previous studies. Trichloroethanol was
      found to be present in the blood, urine, and bile, primarily as the glucuronide
      conjugate. In all species, peak TCA concentrations were observed beyond the
      disappearance of TRI. The AUC for TCE glucuronide is consistent with its acting
      as a precursor for TCA and probably contributes to the continued increase in TCA
      concentration after TRI disappears from the system. Investigations into the
      binding of TCA to plasma constituents in the rat, dog, mouse, and human suggest
      that binding also plays a role in species differences in the distribution and
      elimination of TCA.

PMID- 7723077
TI  - Histone nuclear proteins are irreversibly modified by reactive metabolites of
      diethylstilbestrol.
AB  - We demonstrate for the first time that diethylstilbestrol (DES), a synthetic
      estrogen, is converted by nuclei to histone-binding metabolite(s). Reaction of
      [3H]DES with nuclei in the presence of cumene hydroperoxide or NADPH revealed
      binding of [3H]DES to histone nuclear proteins. Gel electrophoresis experiments
      revealed that all five histones, 1, 2A, 2B, 3, and 4, were irreversibly bound to
      [3H]DES. Histones 1 and 3 were more susceptible to the attack by [3H]DES quinone,
      a metabolite of DES, than histones 2A, 2B, or 4. The kinetic constants, Km and
      Vmax, of this binding reaction in the presence of cumene hydroperoxide were 10
      microM and 750 pmol/mg protein/30 min, respectively. This binding was
      significantly inhibited by cytochromes P-450 inhibitors. Low-molecular-weight
      thiols, such as glutathione and cysteine, or thiol modifiers, such as n
      ethylmaleimide, dithionitrobenzoic acid, and hydroxymercuric benzoate,
      drastically inhibited binding of [3H]DES quinone to histone 3. The binding of
      [3H]DES metabolites to both transcriptionally active and inactive chromatin
      histone proteins was observed. We conclude that DES is metabolized to histone
      binding metabolites, presumably by nuclear cytochrome P-450. DES quinone may be
      one of the histone-binding DES metabolites. These data suggest that an analogous
      in vivo modification in the transcriptionally active chromatin histones by DES
      metabolites may influence gene function.

PMID- 7723078
TI  - Triphenyl phosphite-induced impairment of spatial alternation learning.
AB  - Triphenyl phosphite (TPP) is a weak acetylcholinesterase inhibitor and a type II
      organophosphorus compound-induced delayed neurotoxic agent. The current study
      examined the cognitive effects of a single 250 mg/kg ip dose of TPP administered
      to either 3-mo- or 1-yr-old male Sprague-Dawley rats. Starting 4 d after TPP
      administration, the rats began training on a T-maze spatial alternation task for
      food reinforcement. Over five sessions of acquisition training, the TPP-treated
      rats showed significantly lower alternation scores than controls. There was no
      difference in spatial alternation performance in the first session, when both
      groups were performing at near-chance levels. In sessions 2-5, the controls
      improved dramatically to an average of 85.3 +/- 3.2% correct, while the TPP
      treated rats did not significantly change, with 69.7 +/- 3.1 percent correct.
      During sessions 2 and 3 there was a significant TPP treatment-related deficit.
      This TPP-induced choice accuracy deficit was persistent in that it was seen well
      after the acute exposure. With continued training the TPP-exposed rats were able
      to learn the task as well as controls. There were no significant TPP effects on
      response latency. These data show that acute TPP administration has persistent
      effects of impairing T-maze learning that do not appear to result from effects on
      motor function.

PMID- 7723079
TI  - Teratogenesis induced by short- and long-term exposure of Xenopus laevis progeny
      to lead.
AB  - Short-term (96-h) tests on Xenopus laevis embryos are advocated for rapid
      screening of teratogens, as an alternative to the use of mammals. The objective
      of the present investigation was to determine whether extending the short-term
      tests beyond 96 h would detect the teratogenicity of chemicals that would
      otherwise be missed by the short-term tests. Lead teratogenicity was examined in
      Xenopus, using lead concentrations of 0.02, 0.05, 0.1, 0.5, 1.0, and 3.0 mg/L,
      which bracket the U.S. Environmental Protection Agency (EPA) maximum allowable
      concentration of 0.05 mg/L in water. Short-term exposure times were 72 or 96 h,
      starting on d 1, 2, or 3 postfertilization, while long-term exposure covered d 1
      through metamorphosis. Short-term exposure resulted in neural tube defects (when
      exposure included d 1 and/or d 2) and tail curvatures, but only at the higher
      lead concentrations (1 and 3 mg/L). Lower lead concentrations produced no
      malformations upon short-term exposure, and this corresponded with the absence of
      tissue lead uptake. On the other hand, long-term exposure to lead (> 3 wk)
      resulted in the delayed appearance of lordoscoliosis at low lead concentrations
      (0.02-0.1 mg/L). The delayed appearance of lordoscoliosis corresponded roughly
      with the attainment of stable lead tissue levels, and this malformation persisted
      after metamorphosis. Thus, short-term observation tests alone may fail to detect
      the teratogenicity of low concentrations of environmental chemicals, and may
      result in the setting of inappropriately liberal exposure standards.

PMID- 7723080
TI  - Effects of a secondary-treated thermomechanical pulp mill effluent on aquatic
      organisms as assessed by short- and long-term laboratory tests.
AB  - The chronic effects of secondary-treated effluent from a thermomechanical pulp
      (TMP) mill were assessed by means of long-term and short-term laboratory toxicity
      tests. The effluent used for the tests was sampled at a western Canadian mill
      using mostly softwoods and < 10% recycled fiber as furnish. In the long-term
      test, the effects of the effluent on the life cycle of fathead minnows
      (Pimephales promelas) were studied. In this experiment, which began with the egg
      stage and continued through to sexual maturity and reproduction, the fish were
      exposed in the laboratory to well water (control) and five concentrations (1.25%,
      2.5%, 5%, 10%, or 20%) of effluent for 202 d. None of the effluent concentrations
      significantly affected the hatching of the eggs, the mortality, weight, length,
      gonad size, gender balance, and reproduction of the hatched fish, the prevalence
      of gross morphological and histopathological changes, and the hatchability of the
      first generation eggs. Two short-term tests, each lasting 7 d, were also
      performed. In these tests, 100% effluent caused no change in the survival/growth
      of minnow larvae or in the survival/reproduction of Ceriodaphnia.

PMID- 7723081
TI  - Driver fatalities in 1985-1993 cars with airbags.
AB  - OBJECTIVE: Analyses were conducted to estimate the effectiveness of airbags in
      reducing driver fatalities in motor vehicle crashes. DESIGN: Airbag effectiveness
      was estimated by (1) comparing driver fatalities in frontal crashes with driver
      fatalities in nonfrontal crashes for cars with airbags and manual belts and cars
      with manual belts only, and (2) by comparing driver fatal crash rates per 10,000
      registered vehicles for cars with airbags and manual belts and cars with manual
      belts only. MATERIALS AND METHODS: Fatal Accident Reporting System data for 1985
      1993 model year cars were compared. MEASUREMENTS AND MAIN RESULTS: The two
      methods yielded similar results. In the analysis based on location of damage,
      driver fatalities in airbag equipped cars were reduced by 24 percent in frontal
      crashes relative to comparable cars with manual belts only and by 16 percent in
      all crashes. In the analyses based on vehicle registration data, fatality rates
      for frontal crashes were reduced by 23 percent for cars with airbags and manual
      belts compared with the same cars equipped with manual belts only and by 16
      percent for all crashes. CONCLUSIONS: Various estimates of airbag effectiveness
      are beginning to yield consistent results. These analyses confirm that driver
      airbags are reducing fatalities in the frontal crashes for which they are
      designed.

PMID- 7723082
TI  - Airbag deployments: the Canadian experience.
AB  - Transport Canada is undertaking an in-depth study of motor vehicle collisions
      involving airbag deployments. University-based collision investigation teams
      across Canada are used to collect crash data. The primary objective of the study
      is to gain a better understanding of the injuries and the injury mechanisms
      associated with airbag deployments among both restrained and unrestrained
      occupants. Preliminary results show an exceptionally high level of seatbelt use
      in conjunction with the supplemental air cushion restraints. Most crashes are,
      however, of only minor to moderate severity, in which the seatbelt systems alone
      would be expected to provide adequate occupant protection. Initial findings
      indicate that, at the lower end of the collision severity spectrum, deployment of
      an airbag may, in some circumstances, increase the overall likelihood of injury
      to a restrained occupant. This suggests that the current deployment threshold is
      set too low, at least for belted occupants.

PMID- 7723083
TI  - Upper extremity injuries related to airbag deployments.
AB  - OBJECTIVE: Details on airbag injuries to the upper extremity are relatively
      unknown to clinicians. The injuries presented here should provide a clear
      understanding of the mechanisms of forearm, hand, and wrist injuries that may be
      seen by emergency room physicians. MATERIALS AND METHODS: From our crash
      investigations of 325 airbag-equipped passenger cars, a subset of upper extremity
      injuries are presented that are related to airbag deployments. MAIN RESULTS:
      Minor hand, wrist, or forearm injuries--contusions, abrasions, and sprains--are
      not uncommonly reported. Infrequently, hand fractures have been sustained and, in
      isolated cases, fractures of the forearm bones or of the thumb, wrist, and
      fingers. The close proximity of the forearm to the airbag module door is related
      to most of the fractures identified. Steering wheel airbag deployments can fling
      the hand-forearm into the instrument panel, rearview mirror, or windshield, as
      indicated by contact scuffs, tissue debris, or the star burst (spider web)
      pattern of windshield breakage in fron of the steering wheel. CONCLUSION: Minor
      injuries of the upper extremity can occur when contacted by the deploying airbag
      either directly or by flinging the hand-forearm into interior car structures.
      Fractures of the forearm are rare and usually are due to direct impact by the
      forceful opening of the airbag module door.

PMID- 7723084
TI  - Airbag module cover injuries.
AB  - Serious and fatal injuries can be sustained when anatomic structures are in close
      proximity to an airbag module cover at the moment of airbag deployment. Three
      cases of injuries in vehicle operators associated with airbag module covers are
      reviewed and discussed. Injuries ranged from the traumatic avulsion of a thumb to
      the development of a subdural hematoma with associated cerebral edema and
      respiratory arrest. Motor vehicle operators should be aware that although airbags
      can significantly reduce the severity of injuries sustained in frontal collisions
      the module cover has the potential to inflict serious, even fatal injuries.

PMID- 7723085
TI  - Ocular injuries associated with eyeglass wear and airbag inflation.
AB  - OBJECTIVE: The purpose of this report is to detail three cases of serious ocular
      injury associated with eyeglass wear during airbag inflation following motor
      vehicle crashes. DESIGN: Although there were too few cases to provide valid
      statistics, an attempt was made to determine if there were characteristics common
      to the glasses or accidents that would provide preventive information. MATERIALS
      AND METHODS: The emergency room records were reviewed for a 4-year period and
      cases were extracted involving ocular injuries related to airbag inflation.
      Fourteen cases were found, and three patients were wearing glasses. These cases
      were studied in detail. MEASUREMENTS AND MAIN RESULTS: All three patients
      sustained serious, vision-compromising ocular damage. CONCLUSIONS: Eyeglass wear
      presents an additional risk factor for ocular injury during airbag inflation.
      Frame damage and lens shatter provide potential for both blunt and penetrating
      types of ocular injury.

PMID- 7723086
TI  - Airbag deployment and eye perforation by a tobacco pipe.
AB  - Airbags have been shown to reduce injuries and save the lives of car occupants in
      a crash. Like any protection system, airbags potentially introduce some new risks
      if no appropriate countermeasures are taken. A case of a relatively moderate
      frontal impact is described where the driver of an airbag-equipped car suffered a
      severe penetrating eye injury after the airbag deployed. Since the airbag fabric
      itself was excluded as an injury-producing structure, other objects such as
      eyeglasses, a wrist-watch, a bracelet, and a large finger ring had to be
      assessed. The investigation of the car interior as well as the morphologic
      details of the injuries to the eye and the face revealed that the most likely
      candidate for the injury was a tobacco pipe, which was probably being held in one
      hand and was broken apart by the deploying airbag and projected into the face of
      the driver. This case illustrates the hazard of having any rigid object between
      the occupant and the deploying airbag. The desirability of warning car occupants
      of the potential hazards which can result from today's protection systems is also
      discussed.

PMID- 7723087
TI  - Occult abdominal injuries to airbag-protected crash victims: a challenge to
      trauma systems.
AB  - A multidisciplinary, automobile crash investigation team at the University of
      Miami School of Medicine, William Lehman Injury Research Center of Jackson
      Memorial Hospital/Ryder Trauma Center in Miami, Florida, is conducting a detailed
      medical and engineering study. The focus is restrained (seatbelts, airbag, or
      both) occupants involved in frontal crashes who have been severely injured. More
      than 60 crashes have been included in the study to date. Analysis of the initial
      data supports the general conclusion that restraint systems are working to reduce
      many of the head and chest injuries suffered by unrestrained occupants. However,
      abdominal injuries among airbag-protected occupants still occur. Some are found
      among occupants who appeared uninjured at the scene. Case examples are provided
      to illustrate abdominal injuries associated with airbag-protected crashes. The
      challenges of recognizing injuries to airbag-protected occupants are discussed.
      To assist in recognizing the extent of injuries to occupants protected by
      airbags, it is suggested that evidence from the crash scene be used in the triage
      decision. For the abdominal injury cases observed in this study, deformation of
      the steering system was the vehicle characteristic most frequently observed. The
      presence of steering wheel deformation is an indicator of increased likelihood of
      internal injury. This may justify transporting the victim to a trauma center for
      a closer examination for abdominal injuries.

PMID- 7723088
TI  - Lower extremity injuries in drivers of airbag-equipped automobiles: clinical and
      crash reconstruction correlations.
AB  - OBJECTIVE AND DESIGN: To determine the relationship between airbags and lower
      extremity injuries, 10 drivers admitted to a level-I trauma center with
      substantial lower extremity trauma incurred in crashes involving airbag-equipped
      vehicles were studied in depth with regard to their injuries, the circumstances
      of the crashes, and the medical charges for the acute management of those
      injuries. MATERIALS AND METHODS: During the clinical investigation portion of
      this study, we photographed lower extremity injuries, both soft tissue and
      radiographs, and performed a detailed surgical exploration during the debridement
      of open wounds or fracture fixation to treat them appropriately and to define the
      mechanism of injury, the fracture pattern, the pattern of soft-tissue insult, and
      the extent of periosteal stripping. We recorded the hospital and professional
      charges associated with the acute management not only of these injuries, but of
      the other injuries as well. The analysis performed for each case included a
      detailed crash reconstruction, including force, contact point, and vehicle
      intrusion data. Particular attention was paid to the dashboard and toe pan areas
      to determine deformation and intrusion and their association with thigh, leg, and
      foot injuries. Pertinent deformation and trajectory information was entered into
      the Calspan Reconstruction of Accident Speeds on the Highway (CRASH) computer
      program to generate a delta V or change in velocity measurement used as a measure
      of collision severity. When field data were incompatible with the limitations of
      the CRASH program, manual calculations such as "slide to stop" and conservation
      of momentum formulas were used. RESULTS: The seven male and three female drivers
      had a mean age of 39.4 years. Only four used seatbelt restraints. The mean delta
      V was 28.3 mph and the mean maximum crush was 32.4 inches. The mean Injury
      Severity Score of 13.2. Musculoskeletal injuries included 11 foot/ankle
      fractures, 6 tibial fractures, 2 patellar fractures, 6 femoral fractures, and two
      acetabular/pelvic fractures. Other trauma included abdominal, thoracic, head and
      upper torso injuries, it seems that these safety devices do not prevent injuries
      to the lower extremity.

PMID- 7723089
TI  - Air and knee bolster restraint system: laboratory sled tests with human cadavers
      and the Hybrid III dummy.
AB  - Growing evidence from data base and laboratory studies demonstrates effective
      occupant protection with the airbag supplemental restraint and seatbelt restraint
      system. Concern that drivers of vehicles equipped with airbags may assume
      adequate protection without concomitant seatbelt use prompted the study of
      unbelted occupant behavior in frontal crashes. OBJECTIVE: To evaluate the crash
      protection afforded unbelted drivers in airbag-equipped vehicles. DESIGN: Six
      laboratory sled tests were conducted with a production driver's side airbag and
      knee bolster restraint system but without a seatbelt restraint system. MATERIALS
      AND METHODS: Four human cadavers and the Hybrid III dummy were used as occupants
      in 32 km/h and 48 km/h tests with a simulated mid-size vehicle. MEASUREMENTS AND
      MAIN RESULTS: Head contact with the windshield/header region of the simulated
      vehicle and abdominal impingement on the lower rim of the steering wheel were
      noted in all tests. Autopsy examinations and radiographic images identified
      extensive spinal and thoracic trauma in addition to lower extremity and facial
      injuries. Injury Severity Scores were considered severe to critical for all
      occupants. CONCLUSIONS: The evidence suggests the need to emphasize the use of
      seatbelts in conjunction with airbags and to develop a redesigned airbag and knee
      bolster system to control occupant kinematics and loading more effectively.

PMID- 7723090
TI  - Mechanism of induction of asthmatic attacks initiated by the inhalation of
      particles generated by airbag system deployment.
AB  - OBJECTIVE: We have previously demonstrated that inhalation of the dust produced
      by dual frontal airbag deployment can result in significant bronchospasm in
      approximately 40% of mild to moderate asthmatics. This study was performed to
      determine the cause of the asthmatic response. DESIGN: Controlled laboratory
      study. MATERIALS AND METHODS: Asthmatics who were previously tested for their
      response to airbag effluents were exposed for twenty minutes to either 1) airbag
      effluents from airbag systems in which the airbag was insulated from the hot
      deployment module; 2) non-sulfur containing airbag effluents; 3) sodium chloride
      aerosol; or 4) sodium carbonate-bicarbonate aerosol (pH 10). Pre-exposure, post
      exposure, and 2 hour post exposure pulmonary spirometry and mechanics were
      measured. Subject's filled out symptoms questionnaires before exposure, 2, 4, 8,
      12, and 19 minutes into the exposure, immediately post-exposure, and 2 hours post
      exposure. MEASUREMENTS AND MAIN RESULTS: Prevention of the pyrolysis of the
      passenger-side bag as it rested on the hot module after deployment did not
      diminish the asthmatic response. Removal of sulfur-containing oxidants from the
      airbag pyrotechnic chemistry, which may have led to sulfite production, similarly
      did not alleviate the asthmatic response to the airbag effluents. Lastly, when
      asthmatics were exposed to sodium chloride and sodium carbonate-bicarbonate
      aerosols at approximately the same concentration (approximately 220 mg/m3) as the
      airbag aerosol concentration that occurred in the in-car tests, they had
      responses similar to those produced by the airbag exposures. CONCLUSIONS: We
      conclude that the amount of soluble particulate contained in the aerosol
      discharged into the passenger compartment by dual frontal airbag deployment is
      largely the cause of the observed evoked asthmatic attacks. The alkaline pH of
      the airbag and carbonate aerosols may have added an additional degree of
      provocation.

PMID- 7723091
TI  - Physical and chemical characterization of airbag effluents.
AB  - OBJECTIVE: This paper describes a study aimed at characterizing the exposure to
      physical and chemical by-products from the deployment of airbag restraint
      systems. DESIGN, MATERIALS AND METHODS: Specifically, the levels of particulates
      and the composition of gases and bag fabric speed were measured in the passenger
      compartment following deployment of either a driver's side or driver's
      side/passenger's side airbag system. MEASUREMENTS: A Fourier transform infrared
      analyzer (FTIR) and chemiluminescence analyzers were used for gas analysis, a
      cascade impactor and gravimetric filter measurements for aerosol determination
      and high-speed films to determine fabric speed. MAIN RESULTS AND CONCLUSIONS: The
      measured gases were found to be within the recommended guidelines for human
      exposures, but no guidelines exist for particle exposures of this magnitude (150
      220 mg/m3) but short duration. High-speed films were also taken of the
      deployments to obtain an estimate of the fabric speed as it leaves the module.
      The maximum average speed for both types of airbag was approximately 100 mph and
      in both cases average speeds ranged from lows near 50 mph to highs of over 200
      mph.

PMID- 7723092
TI  - The limitations of current seatbelts in Europe--some population considerations.
AB  - Seatbelts are most likely to function as they were designed if the car occupants'
      survival space remains uncompromised during an impact. Crashed cars with
      negligible passenger compartment intrusion were used to study seatbelt
      effectiveness in that situation. Belted front seat occupants were investigated
      together with their front impacted vehicles. Current model seatbelts were seen to
      prevent many more forward contacts than those seen in a similar study 15 years
      ago. In the earlier study, head contacts occurred to 65% of drivers whereas the
      current sample contained 24%. The present study also found that thigh or knee
      contacts were common occurrences for drivers and front seat passengers, as were
      thoracic injuries caused by loads from the belt itself and neck injuries caused
      by deceleration. The results emphasize how real people, unlike crash test
      dummies, have varied characteristics that influence seatbelt performance.

PMID- 7723093
TI  - Restraint effectiveness, availability and use in fatal crashes: implications to
      injury control.
AB  - The effectiveness and benefits of occupant restraint systems are compared by
      seating position in motor vehicles. While safety belts are 42% effective in
      preventing fatalities, the addition of the driver side airbag provides a 12%
      increase in effectiveness. The implications of safety belt use and airbag
      availability over the next decade are considered for fatal injury prevention. The
      analysis includes theoretical relationships and forecasts fatality prevention as
      lap-shoulder belt use increases and airbags phase into the vehicle fleet.

PMID- 7723094
TI  - Vertebral column injuries and lap-shoulder belts.
AB  - OBJECTIVE: To present cases of vertebral column fractures or fracture
      dislocations that occur to restrained front seat occupants where there is no
      evidence of body contact with interior car components based on both medical
      records and car inspection. MATERIALS AND METHODS: Reviewed were car crash injury
      cases investigated at the University of Michigan Transportation Research
      Institute and at the University of Birmingham (England) as well as the National
      Accident Severity Study files of the National Highway Traffic Safety
      Administration. Medical records and car inspections in the cases presented did
      not indicate any evidence of body contact with interior car structures. MAIN
      RESULTS: Vertebral fractures or fracture dislocations sustained by front seat
      occupants who were wearing lap-shoulder belts are rare, as evidenced by the
      relatively few cases identified in the literature and in the crash injury files
      reviewed. CONCLUSIONS: Infrequently, in frontal crashes, vertebral fractures or
      fracture dislocations can occur to lap-shoulder belted front seat car occupants
      without head or torso impacts with interior car structures. Cervical spine
      injuries are due to neck flexion over the shoulder portion of the restraint.
      Thoracolumbar fractures can occur in the frontal crash even at low crash
      velocity.

PMID- 7723095
TI  - The influence of increased roof strength on belted and unbelted dummies in
      rollover and drop tests.
AB  - This report condenses and summarizes two related and previously published
      reports. These two reports analyzed the effect of added roof strength on both
      belted and unbelted dummies. The reports, which have been dubbed Malibu I and
      Malibu II, respectively, presented data from a total of 16 rollover crash tests
      and four test conditions in which vehicles were dropped on their roofs. To
      evaluate the effect of roof strength, half of all test vehicles were modified to
      incorporate rigid rollcages, the other half were production vehicles. To evaluate
      the effect of belt restraints, half of all tests incorporated restrained dummies,
      the other half were unrestrained. The data from these tests clearly demonstrated
      that increased roof strength provided no reduction in dummy neck loads for belted
      or unbelted dummies when they were located over the area of the roof that
      impacted the ground. The tests also demonstrated that the neck loads resulted
      from "diving" type impacts, where the head stops and the torso momentum loads the
      neck. Roof deformation never caused the dummy to be compressed between the roof
      and seat.

PMID- 7723096
TI  - Humanitarian benefits of cadaver research on injury prevention.
AB  - This paper discusses the value of human cadaveric subjects in injury biomechanics
      research. Published data were used to estimate the number of cadavers used in the
      past 30 years and to show that, as a benefit to society, over 60 lives were saved
      and countless injuries prevented for each cadaver used in the development and
      validation of safety improvements. Ethical and religious concerns regarding the
      use of cadavers are also addressed. Because of the substantial humanitarian value
      of cadaver research and the lack of suitable specimens, it is proposed that
      cadaver resources be pooled and that institutions with surplus specimens supply
      the few cadaver testing laboratories with specimens each year. This approach will
      enable further development of safety systems and facilitate achieving the
      national goals for injury control.

PMID- 7723097
TI  - Research in biomechanics of occupant protection.
AB  - This paper discusses the biomechanical bases for occupant protection against
      frontal and side impact. Newton's Laws of Motion are used to illustrate the
      effect of a crash on restrained and unrestrained occupants, and the concept of
      ride down is discussed. Occupant protection through the use of energy absorbing
      materials is described, and the mechanism of injury of some of the more common
      injuries is explained. The role of the three-point belt and the airbag in frontal
      protection is discussed along with the potential injuries that can result from
      the use of these restraint systems. Side impact protection is more difficult to
      attain but some protection can be derived from the use of padding or a side
      impact airbag. It is concluded that the front seat occupants are adequately
      protected against frontal impact if belts are worn in an airbag equipped vehicle.
      Side impact protection may not be uniform in all vehicles.

PMID- 7723098
TI  - Automotive airbag-related upper extremity injuries: a report of three cases.
AB  - Automotive airbag technology has reduced the number of injuries and fatalities
      resulting from motor vehicle crashes. With the increasingly frequent application
      of this safety feature in automobiles, recent reports of airbag-associated
      injuries have emerged, including ocular and non-lethal cardiac trauma. We report
      three cases of airbag-related upper extremity injuries seen at a level-I trauma
      center over a 6-month period. A heightened awareness of this type of injury in
      patients injured in motor vehicle crashes with airbag deployment is recommended.
      The awareness, identification, and management of these high energy injuries will
      take on added meaning as the airbag technology becomes universally applied.

PMID- 7723099
TI  - Retinal hemorrhage secondary airbag-related ocular trauma.
AB  - A case is presented in which a driver, who was wearing a three-point restraint
      system, was involved in a collision that triggered deployment of the vehicle's
      driver's-side airbag. The victim complained of blurred vision after the crash and
      on examination was found to have suffered a retinal hemorrhage in his right eye.
      Since no other cause could be determined, his injury was considered to be a
      result of contact with the deploying airbag.

PMID- 7723100
TI  - Accuracy of emergency physician data collection in automobile collisions.
AB  - OBJECTIVE: Triage decisions must be based on accurate information with a valid
      understanding of injury patterns and their sources. Only a data base that
      includes both medical and collision factors can best provide the breadth of
      information required to achieve this goal. In the study reported here we assessed
      the accuracy of automobile collision data collected by emergency physicians
      compared with Police Accident Reports. DESIGN: Prospective study in which
      emergency medicine attending physicians completed questionnaires placed near the
      entrance to the trauma rooms in the emergency department. MATERIALS AND METHODS:
      During a two-month period the emergency medicine attending physicians obtained
      data concerning vehicle collision factors for all automobile collisions resulting
      in major trauma to patients over 18 years of age who were triaged to the
      Emergency Department at Stanford University Hospital, a level-I trauma center.
      These data were then compared by one of the investigators with the data contained
      in Police Accident Reports, which were available for 50 of the 64 patients who
      met the study eligibility criteria. MEASUREMENTS AND MAIN RESULTS: For each
      automobile collision, the attending physician was asked to collect the following
      data: direction of impact; extrication required; ejection; type and use of
      restraints; deployment of an airbag; type of vehicle; reported severity (minor,
      moderate, or major) of impact; presence and degree of steering wheel deformation;
      presence and degree of intrusion into occupant compartment; estimated speed and
      collision type (i.e., vehicle to vehicle, to fixed object, etc.) Nearly three
      fourths (74%) of all cases had at least one discrepancy when compared with the
      Police Accident Reports, while 46% of these had multiple discrepancies.
      CONCLUSIONS: When data obtained by emergency physicians are compared with the
      information in Police Accident Reports, there are notable differences on several
      collision factors. Triage decisions must be based on accurate information with a
      valid understanding of injury patterns and their sources. Only a data base that
      includes both medical and collision factors can best provide the breadth of
      information required to achieve this goal.

PMID- 7723101
TI  - Anterior lung herniation: another aspect of the seatbelt syndrome.
AB  - Shoulder harnesses can be a source of thoracic injury in motor vehicle crashes.
      Sternal and rib fractures are most commonly reported. We present a case of a
      traumatic anterior lung herniation secondary to shoulder harness trauma in a
      motor vehicle crash victim with multiple injuries. A brief review of lung hernias
      is provided as well as a brief discussion of the thoracic manifestations of the
      seatbelt syndrome.

PMID- 7723102
TI  - Injury severity and probability of survival assessment in trauma patients using a
      predictive hierarchical network model derived from ICD-9 codes.
AB  - Accurate assessment of injury severity is critical for decision making related to
      the prevention, triage, and treatment of injured patients. Presently, the
      standard method of controlling for variations of injury severity between groups
      has been based upon the Injury Severity Score (ISS) and the Trauma Score and the
      Trauma and Injury Severity Score (TRISS) methodology. The purpose of this study
      was to attempt to build upon previous work using International Classification of
      Diseases, ninth revision (ICD-9) coded diagnosis, and procedure information
      available from standard hospital discharge abstracts (UB-82 Billing format) to
      create a hierarchical network to provide a tool for predicting injury severity
      and probability of survival. METHODS: Data were obtained for this analysis from
      the North Carolina Medical Database. Data were available on all trauma patients
      admitted to hospitals in North Carolina from January 1, 1988 until June 30, 1992.
      The dependent variable of interest was the patient's survival after injury, coded
      as live or die. The independent variables used in the study included the ISS
      derived using the technique described by MacKenzie Abbreviated Injury Score (AIS)
      and body system maximum AIS scores, mortality risk ratios derived from the ICD-9
      DM primary, secondary, and tertiary diagnoses, primary and secondary procedures
      as described in previous work, age and gender. Network generation used a
      commercial software package, AIM (Abtech Corp., Charlottesville, Va.), which is a
      numeric modeling tool that automatically "learns" knowledge from a data base of
      examples. RESULTS: In the test data set an ISS and a prediction of survival based
      upon the derived network were calculated for each and every patient. The relative
      predictive power of these two scores were compared by calculating the overall
      accuracy, sensitivity, and specificity and the false positive and false negative
      rates. The receiver operator characteristic curves demonstrate that the network
      is a more effective tool in predicting the outcome of trauma patients. All the
      measures of predictive power show that the network was the better predictor of
      outcome than the ISS. CONCLUSIONS: Given the recognized limitations of the ISS,
      the widespread availability of the ICD-9 coded diagnoses and procedures, and the
      availability of many state and regional data bases that have no ISS or Trauma
      Score, the purpose of this study was to assess the ability of a network derived
      from limited but widely available hospital discharge data to predict the outcome
      of injured patients. The study confirms previous work showing that the ICD-9
      codes were strongly associated with outcome. The study demonstrated that the
      network created from these data was a better predictor of outcome than the
      derived ISS. When the results of the network were compared with other published
      series, the network, created without access to physiologic information, was
      almost as accurate, sensitive, and specific as reported values for TRISS and A
      Severity Characterization of Trauma (ASCOT). Because the present study is the
      first of its type, further investigations are needed to validate these findings.
      If other studies corroborate this study, a network model based upon ICD-9 codes
      could become the principal method for grading injury severity. This would provide
      superior predictive power of injury severity with important cost savings and
      universal application.

PMID- 7723103
TI  - Deep hypothermic circulatory arrest for blunt retrohepatic venous injury: a case
      report.
AB  - A case of major blunt hepatic injury requiring liver resection is described. An
      associated retrohepatic vena cava injury could not be repaired despite the use of
      an atriocaval shunt. Deep hypothermic circulatory arrest was used as a last
      resort.

PMID- 7723104
TI  - Fluid and electrolyte deficit with prolonged pneumatic antishock garment
      application.
AB  - OBJECTIVE: When trauma victims are within 1 hour of definitive surgical care,
      prehospital pneumatic antishock garment (PASG) application has not improved
      outcome. A resuscitative role for PASG has been suggested when transport time is
      longer (e.g., 4 hours). We assessed the fluid and electrolyte cost of treating
      posthemorrhagic hypotension with the PASG in 16 anesthetized Yorkshire piglets
      (30 to 32 kg). DESIGN: Hypotension [30 mm Hg drop in carotid arterial blood
      pressure (CBP)] was produced by arterial line bleeding. Hemodynamics, serum
      electrolytes, lactate, and tissue edema (limb circumference) were monitored.
      MATERIALS AND METHODS: In eight animals (group 1), PASG was inflated to maintain
      prebleed CBP for 4 hours. In group 2, the hypotension was untreated for 4 hours.
      After 4 hours, shed blood (over a period of 15 minutes) and normal saline (1.5
      mL/kg/minute) were infused until CBP returned to normal baseline values.
      MEASUREMENTS AND MAIN RESULTS: Shed blood alone did not restore baseline CBP.
      Serum K+ increased from a baseline of 3.9 to 9.1 mmol/L in group 1, with no
      significant change in group 2. Serum lactate rose from 1.8 to 24.1 and from 1.7
      to 6.8 mmol/L in groups 1 and 2, respectively. After 4 1/2 hours, an increase in
      thigh circumference (6.4 +/- 1.4 vs. 1.9 +/- 1.0 mm) and intravenous fluid
      required after returning shed blood (626 +/- 36 vs. 324 +/- 22 mL) was greater in
      group 1 (means +/- SD, p < 0.05). Other serum electrolyte values were similar for
      the two groups. CONCLUSIONS: We conclude that fluid deficit, lactic acidosis,
      tissue edema, and hyperkalemia are all greater with prolonged PASG application
      when compared with the untreated hypotensive state. These findings must be
      considered when suggesting more prolonged PASG application.

PMID- 7723105
TI  - Pneumatic antishock garment-associated compartment syndrome in uninjured lower
      extremities.
AB  - Pneumatic antishock garment-associated compartment syndrome is a rare and yet
      underrecognized complication that when it occurs, frequently results in
      myonecrosis and loss of limb function, and occasionally loss of a limb or even
      death. We report a case of pneumatic antishock garment-associated compartment
      syndrome in a trauma patient without lower extremity injury and review similar
      published reports. It is only with a high index of suspicion, early recognition,
      and prompt treatment of this complication by fasciotomy and proper wound care
      that associated morbidity and potential mortality of this complication can be
      prevented or minimized.

PMID- 7723106
TI  - Subclavian-carotid transposition: an option for repair of traumatic subclavian
      artery dissection: case report.
AB  - An extremely rare injury, dissection of the subclavian artery from blunt trauma,
      is reported. Arterial flow to the upper extremity was restored by subclavian
      carotid transposition, obviating the need for prosthetic graft repair. Subclavian
      carotid transposition is a useful technique in the repair of selected subclavian
      artery injuries.

PMID- 7723107
TI  - Clinical application of the distally based medial adipofascial flap for soft
      tissue defects on the lower half of the leg.
AB  - OBJECTIVE: Reconstruction of soft tissue defects on the lower half of the leg.
      DESIGN: The distally based medial adipofascial flap nourished by the lower
      perforator originating from the posterior tibial artery was harvested, and the
      pivot point of flap transposition is 9 to 12 cm above the tip of the medial
      malleolus. MATERIALS AND METHODS: Twelve cases of open tibial fracture associated
      with soft tissue defects on the lower half of the leg were reconstructed with
      this flap. The cases consisted of ten males and two females, and their ages
      ranged from 16 to 71 (averaging 41 years). MEASUREMENTS AND MAIN RESULTS: Size of
      the flap varied from 4 x 7 cm to 5 x 18 cm. Eleven flaps had good perfusion and
      survived completely. Tip necrosis of the flap occurred in one case. In the early
      postoperative period, take of the meshed split-thickness skin graft on the flap
      was not complete. All wounds, however, were resurfaced completely without the
      need of a second grafting. Discharging sinuses occurred in one case, which was
      managed by removal of infected bony fragments. All the donor sites were closed
      primarily, and desquamation of wound edges occurred occasionally. CONCLUSIONS:
      The distally based medial adipofascial flap was a reliable and effect local flap
      for the reconstruction of soft tissue defects on the lower half of the leg.

PMID- 7723108
TI  - Early diagnosis of small intestine rupture from blunt abdominal trauma using
      computed tomography: significance of the streaky density within the mesentery.
AB  - Enhanced computed tomography (CT) was done in 430 patients within 3 hours after
      blunt abdominal trauma. Thirteen patients were found to have ruptures of the
      small intestine. Nine of them had "the streaky density within the mesentery" and
      the position was identified by tracing the alimentary tract on each CT slice. The
      sensitivity and specificity of this sign was 69 and 100% respectively. The
      sensitivity for diagnosis of small intestinal rupture by the presence of this
      sign and/or free air was 85%. This was significantly higher than that of free air
      alone (p < 0.05). Eight patients had a rupture on a mesenteric site.
      Histopathological findings of the area with this sign included bleeding and
      cellular infiltration along the mesenteric vasculature. This appearance may be
      related to direct injury and chemical irritation of the mesentery caused by
      intestinal rupture. The streaky density appears to be a significant finding for
      small intestinal rupture.

PMID- 7723109
TI  - Combined hepatic abscess and arterial pseudoaneurysms from blunt trauma: a case
      report and management strategy.
AB  - Hepatic abscess is a known complication following packing for massive liver
      injury. Posttraumatic hepatic arterial pseudoaneurysms are rare. The trend in
      management in each individual complication has been toward minimally invasive
      techniques. We present a case wherein the two processes occurred together and
      were managed safely with a transcatheter approach.

PMID- 7723110
TI  - Open tibia fractures in the splenectomized trauma patient: results of treatment
      with locking, intramedullary fixation.
AB  - OBJECTIVE: To confirm our clinical impression that patients with traumatic
      splenectomy had more complications in the treatment of open tibia fractures, we
      retrospectively reviewed the records of patients with open tibia fractures
      treated between 1989 and 1992. MATERIALS AND METHODS: Eight patients with open
      tibia fractures and traumatic splenectomies were compared to 43 patients with
      open tibia fractures and intact spleens. The latter group typically underwent
      either exploratory laparotomy or peritoneal lavage. The two groups were similar
      with respect to age, mechanism of injury, fracture wound classification, and
      injury severity score (22.4 in the splenectomized patients, 18.6 in the control).
      All tibia fractures were treated with a nonreamed, cross-locked, titanium
      intramedullary nail, and all patients were treated according to the same protocol
      of antibiotic therapy. Patients were followed for two years or until
      roentgenographic and clinical union. RESULTS: The splenectomized patients had a
      significantly higher incidence of chronic osteomyelitis (25% vs. 4.6%), and the
      need for additional tibial surgeries to achieve union (75% vs. 16%). Time to
      union averaged 11.3 months in the splenectomized group and 7.6 months in the
      patients with intact spleens. CONCLUSIONS: The increased risk for chronic
      osteomyelitis and other complications of tibial fracture in the splenectomized
      patients should be taken as an argument favoring splenic, repair, when possible,
      rather than splenectomy in victims of blunt multiple trauma.

PMID- 7723111
TI  - Fracture of the anterior colliculus.
AB  - The authors retrospectively reviewed 33 cases of fracture involving the anterior
      colliculus of the medial malleolus to examine clinical results of operative
      treatment for these fractures. Although this injury appears innocuous, it can be
      difficult to obtain stable fixation of the fragment intraoperatively, and painful
      nonunion can result. A simple reduction maneuver and method of tension band
      fixation are described.

PMID- 7723112
TI  - External fixation of open femoral shaft fractures.
AB  - OBJECTIVE: To determine whether external fixation proves to be a sensible
      technique for definitive stabilization in open femoral fractures. DESIGN:
      Retrospective clinical study. MATERIALS AND METHODS: From 1985 to 1989, 18
      patients (mean ISS 25.4) with open femoral fractures (type II 11%, type III 89%)
      were treated by primary and definitive external fixation. After failure of closed
      reduction procedures, open reduction via debrided soft tissue wounds was employed
      in 72%. Supplemental internal fixation of large wedge fragments was required in
      66%. External fixators were removed after a mean of 166 days. Early deep
      infections developed in 11%. Additional cast, brace, or traction were not
      required. MEASUREMENTS AND MAIN RESULTS: After a mean follow-up period of 58
      months, 88% of the surviving 17 patients were clinically and radiologically
      evaluated and 12% were interviewed by telephone. Eleven percent developed late
      deep infection of the femur concerned. Eighty percent have had full or slightly
      restricted knee motion. The mean knee flexion amounted to 130 degrees. Relevant
      shortening of the femur was diagnosed in 7%. Nonunions or relevant malunions were
      not observed in our series. CONCLUSIONS: These morphologic and functional results
      compare with those published for alternative stabilization techniques of femoral
      fractures. For special indications, external fixation is considered to be a
      sensible technique for primary and definitive treatment of open femoral
      fractures.

PMID- 7723113
TI  - Posterior cruciate avulsion fracture associated with a large inverted medial
      tibial osteochondral fragment.
AB  - A case of traumatic avulsion fracture of the posterior cruciate ligament in
      association with a large osteochondral fracture of the medial tibial condyle is
      described. The osteochondral fragment was inverted 180 degrees. Many associated
      injuries of the posterior cruciate ligament have been described. This unusual
      combination of fractures to the best of our knowledge has not been reported
      before. The mechanism of injury and its clinical implications are discussed.

PMID- 7723114
TI  - Unusual posterior hip dislocation with ipsilateral fractures of the femoral neck
      and head.
AB  - An unusual combination of posterior hip dislocation with ipsilateral femoral neck
      and head fractures is reported. The femoral head migrated too far inferiorly in
      the posterior part of the thigh, making it different from the previously reported
      solitary case report of obturator hip dislocation associated with femoral neck
      and head fractures.

PMID- 7723115
TI  - Free flap reconstructions of tibial fractures complicated after internal
      fixation.
AB  - The cases of 15 patients are presented where microvascular soft-tissue
      reconstructions became necessary after internal fixation of tibial fractures.
      Primarily, seven of the fractures were closed. Eleven fractures had originally
      been treated by open reduction and internal fixation using plates and screws, and
      four by intramedullary nailing. All of the patients suffered from postoperative
      complications leading to exposure of the bone or fixation material. The internal
      fixation material was removed and radical revision of dead and infected tissue
      was carried out in all cases. Soft tissue reconstruction was performed using a
      free microvascular muscle flap (11 latissimus dorsi, three rectus abdominis, and
      one gracilis). In eight cases the nonunion of the fracture indicated external
      fixation. The microvascular reconstruction was successful in all 15 patients. In
      one case the recurrence of deep infection finally indicated a below-knee
      amputation. In another case, chronic infection with fistulation recurred
      postoperatively. After a mean follow-up of 26 months the soft tissue coverage was
      good in all the remaining 13 cases. All the fractures united. Microvascular free
      muscle flap reconstruction of the leg is regarded as a reliable method for
      salvaging legs with large soft-tissue defects or defects in the distal leg. If
      after internal fixation of the tibial fracture the osteosynthesis material or
      fracture is exposed, reconstruction of the soft-tissue can successfully be
      performed by free flap transfer. By radical revision, external fixation, bone
      grafting, and a free flap the healing of the fracture can be achieved.

PMID- 7723116
TI  - Patellar tendon rupture in identical twins.
AB  - We report on identical traumatic injuries in a pair of monozygotic (identical)
      twins treated at the same unit, one year apart. Both had sustained a complete
      tear of the patellar tendon and were treated surgically.

PMID- 7723117
TI  - Intra-articular histopathologic changes secondary to local lead intoxication in
      rabbit knee joints.
AB  - OBJECTIVE: To study the effects of intra-articular lead fragments on articular
      cartilage, synovium, and menisci in rabbit knees. DESIGN: Animal model. MATERIALS
      AND METHODS: Cylindrical lead implants were inserted into a nonarticulating area
      of the medial femoral condyle. Identically sized stainless steel implants were
      used as a control for the mechanical effects of the material, and arthrotomies
      were performed on some of the animals as a control for the effects of surgery.
      MEASUREMENTS AND MAIN RESULTS: Histologic evidence of articular degeneration was
      significantly greater in rabbit knees implanted with lead compared with knees
      with steel implants (p = 0.0625), knees with arthrotomies, or those with no
      procedure performed (p = 0.0325). Changes were also greater in the synovium of
      knees implanted with lead compared with all other specimens. No significant
      degenerative changes were noted in the menisci of any specimen. CONCLUSIONS: Such
      changes may be early signs of degenerative joint disease and may lead to chronic
      damage. Gunshot wounds affecting joints may cause intra-articular retention of
      lead fragments, which are not physiologically inert and may cause degenerative
      joint changes. Even if no mechanical impingement is evident, removal of lead may
      be warranted to prevent early arthropathies in humans.

PMID- 7723118
TI  - Costs of treating gunshot and stab wounds.

PMID- 7723119
TI  - Costs of treating gunshot and stab wounds.

PMID- 7723120
TI  - Costs of treating gunshot and stab wounds.

PMID- 7723121
TI  - Complications of negative laparotomy for abdominal stab wounds.

PMID- 7723122
TI  - DVT prophylaxis in multiple trauma patients.

PMID- 7723123
TI  - ABO-haemolytic disease of the newborn (ABO-HDN): factors influencing its severity
      and incidence in Venezuela.
AB  - The objective of this study was to determine the incidence of the Haemolytic
      Disease of the Newborn due to ABO blood group incompatibility (ABO-HDN) in the
      population of Caracas attending the Maternity Hospital 'Concepcion Palacios'. The
      relationship between A and B antigens density of cord blood erythrocytes and the
      cytotoxic activity of antibodies in mothers' sera with the severity of the
      haemolytic disease, was also studied. From a sample of 245 blood group 'O'
      mothers, 68 gave birth to full term 'A' or 'B' blood group infants. The evolution
      of serum bilirubin and the routine haematological values, were followed in all
      the babies during 72 h after birth, allowing the diagnosis of ABO-HDN in 21
      infants. Taking into account that in Venezuela the frequency of blood group 'O'
      is 59 per cent, it was concluded that in the general population of newborns, 16
      per cent present foeto-maternal ABO incompatibility, and the incidence of ABO-HDN
      was near to 5 per cent. The density of the 'A' and 'B' antigens in cord red cells
      was studied using an immunoenzymatic assay. No statistically significant
      association between antigen maturity and severity of the ABO-HDN could be shown.
      A positive association was found between cytotoxic capacity of mothers' sera and
      development of ABO-HDN (P < 0.05). Twenty ABO incompatibles children presented
      moderate late anaemia at 3 weeks of age.

PMID- 7723124
TI  - Breastmilk immunology.

PMID- 7723125
TI  - Nutritional status and cutaneous leishmaniasis in rural Ecuadorian children.
AB  - The relationship between nutritional status and cutaneous leishmaniasis (CL) was
      evaluated in 230 children living in a rural subtropical rainforest in Northwest
      Ecuador. One-third of the subjects had evidence of either current (13 per cent)
      or past CL infection (21 per cent). Subjects with current (4.71 +/- 0.44 mg) or
      previous disease (4.29 +/- 0.35 mg) had lower mean daily dietary iron intakes
      than non-infected children (5.45 +/- 0.2 mg; chi 2 = 0.048), but not energy,
      protein, or other micronutrients. The low dietary iron intake data was
      corroborated by the reduced mean haemoglobin values observed in children with
      current (11.7 +/- 0.3 mg/dL) or past infection (11.3 +/- 0.2 mg/dL) compared to
      non-infected subjects (12.7 +/- 0.15 mg/dL; F-ratio = 17.0, P < 0.0001). Mean
      hematocrit values were also lower in the two infected groups (37.4 +/- 0.9 per
      cent and 37.4 +/- 0.6 per cent v. 39.5 +/- 0.5 per cent; F-ratio = 4.23, P =
      0.0175). Furthermore, they were more likely to suffer from iron-deficiency
      anaemia than their non-infected counterparts (chi 2 = 4.64, P = 0.03). However,
      the children with active disease accounted for most of the excess risk for anemia
      (Fisher's exact test P = 0.009; OR = 10.0, exact 95 per cent CI = 1.37-111.8).
      Finally, growth stunting (< -2SD height-for-age) was more common in subjects with
      current (54 per cent) or past infection (51 per cent) compared to those without
      CL history (31 per cent; chi 2 = 8.03, P = 0.004).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7723126
TI  - Prolonged breastfeeding without the introduction of supplementary feeding.
AB  - A study on the determinants of nutritional marasmus (NM) and kwashiorkor (K) was
      conducted using Sudanese children aged 6-36 months. The hypotheses tested were
      related to the specific circumstances leading to the development of NM and K.
      Subjects consisted of 55 children with NM and 55 with K, admitted to the
      Children's Emergency Hospital in Khartoum. This paper presents the results of the
      association between NM and prolonged breastfeeding without introduction of
      supplementary feeding between the ages of 6 and 24 months. Mothers were
      interviewed in hospital, and information on duration of breastfeeding, age at
      introduction of supplementary foods, and weaning foods was obtained. Observations
      were made in 20 per cent of homes of study children. The results suggest a
      positive association between prolonged breastfeeding without introduction of
      supplementary feeding between the ages of 6 and 24 months, and NM. Using
      multivariate analysis the data show that late introduction of supplementary foods
      produces an increase of 1.4-fold the odds of developing nutritional marasmus,
      rather than kwashiorkor. In contrast the odds ratio is 1.9 for the two conditions
      in terms of age of cessation of breastfeeding, the kwashiorkor children
      breastfeeding for fewer months. Results suggest strategies to reduce the
      prevalence of NM and K, plus mild and moderate PEM.

PMID- 7723127
TI  - Chest and mid-arm circumferences: identification of low birth weight newborns in
      Turkey.
AB  - The present study was performed to find out which anthropometric measurement(s)
      could efficiently be substituted for weight to detect neonates with low birth
      weight at birth. A total of 874 neonates, between 32 and 43 weeks of gestational
      age were measured within 24 h of birth to interpret the validity of
      anthropometric measurements. Low birth weight was observed in 10 per cent of the
      neonates. The study showed a significant correlation (P < 0.001) between chest
      circumference, mid-arm circumference, head circumference, length, and birth
      weight. However, the correlation was maximum for chest circumference (r = 0.855)
      and mid-arm circumference (r = 0.791). A chest circumference of < 30 cm and a mid
      arm circumference of < 9 cm had the best sensitivity and specificity for
      identifying neonates with a birth weight of < 2500 g. Chest circumference and/or
      mid-arm circumference can be used as simple and reliable indicators for
      predicting low birth weight whenever weighing of newborns is not feasible.

PMID- 7723128
TI  - A normative study of child development using a culture-appropriate test battery
      in rural Haryana, India.
AB  - A culture-appropriate and simple test battery consisting of 67 test items was
      developed and field tested in Haryana, India, in 1987-89. Trained field workers
      administered the tests to 3731 preschool children in 47 randomly selected
      villages of a district, irrespective of their physical/mental status. Centile age
      values were constructed for various developmental milestones included in the
      cultural-appropriate test battery. The locally relevant, simple, and low cost
      developmental tests and reference values will be used for early detection of
      developmental disabilities at primary care level.

PMID- 7723129
TI  - The female street children of Rio de Janeiro: a qualitative study of their
      backgrounds.
AB  - A study of female street children using qualitative methodology revealed a family
      background of poverty, neglect, and violence as key factors in girls taking to
      the streets. Lack of any form of services, either social or medical, which could
      provide a safety net around dysfunctioning families was striking. The role of
      Maternal and Child Health Services in addressing the problem of street children
      is discussed.

PMID- 7723130
TI  - Prevalence of intestinal parasites in Saudi children: a community-based study.
AB  - A community-based study was undertaken to determine the prevalence and types of
      intestinal parasites in the pediatric population of Al-Baha region, Saudi Arabia.
      Stool samples were randomly collected from 19,939 children of whom 4208 (21.1%)
      were found to harbour intestinal parasites. The most affected age group was 5-9
      years and the sex distribution was almost equal in all age groups. Specific
      prevalence rates were Giardia lamblia 9 per cent, entamoeba histolytica 5 per
      cent, Hymenolepis nana 2 per cent, and Enterobius vermicularis 2 per cent. The
      findings of this survey confirm the extremely complex nature of parasitic profile
      in developing communities, and indicate that relationships exist between cultural
      and ecological factors, sanitation, and observed pattern of intestinal parasites.

PMID- 7723131
TI  - Birth asphyxia in a rural community of north India.
AB  - A community-based inquiry was conducted in a rural area of north India to
      estimate extent of the problem of birth asphyxia. Births and neonatal deaths were
      recorded in 54 villages. Trained field workers contacted birth attendants/family
      members within 15 days after the birth, and recorded the symptoms and signs
      related to birth asphyxia on a pre-coded questionnaire. Detailed descriptive
      history of birth events in chronological order was recorded in cases suspected to
      be asphyxiated or stillborn. Two pediatricians reviewed the case histories
      independently to assign the diagnosis. Out of the 1977 recorded livebirths, field
      workers suspected 53 babies to be asphyxiated, 39 of these were diagnosed as
      asphyxiated, four as not asphyxiated by both the experts, and 10 were considered
      as asphyxiated by one of the experts. Prevalence of birth asphyxia was estimated
      to be at least 2 per cent (39/1977). Case fatality in these cases was 74 per
      cent. The verbal diagnosis method adopted in this study can be used to compare
      the prevalence of asphyxia in community studies.

PMID- 7723132
TI  - Incidence of bacteraemia among children with severe anaemia in Wesley Guild
      Hospital, Ilesa, Nigeria.
AB  - One-hundred-and-fifty-two severely anaemic patients, aged 6 months to 14 years
      were studied with a view to ascertaining the incidence of bacteraemia in them.
      Haemoglobin genotype AA was seen in 68 (45 per cent) of the patients, 38 (25 per
      cent) patients were of haemoglobin genotype SS; 35 (23 per cent) patients were of
      haemoglobin genotype AS; three (2 per cent) patients were of haemoglobin genotype
      AC and eight (5 per cent) patients were of haemoglobin genotype SC. Positive
      blood cultures were obtained in a total of 15 (10 per cent) patients. Of these 15
      patients, 10 (22 per cent) patients were sicklers (9 HbSS; 1 HbSC) of a total of
      46 sicklers studied. The remaining five (5 per cent) patients that had positive
      blood cultures were non-sicklers out of a total of 106 non-sicklers studied.
      There was a statistically significant difference between the sicklers and non
      sicklers who had positive blood cultures (P < 0.05). The presence or absence of
      positive blood culture did not correlate with the severity of anaemia in either
      the sicklers or the non-sicklers. It is suggested that any severe anaemic patient
      with clinical features suggestive of sickle cell anaemia must have a blood
      culture done in the course of management. An 'identify at all costs' approach
      should not apply to severe anaemic children who are non-sicklers. The yield is
      low and cost high, clinicians should be selective in deciding in which patients
      blood cultures are warranted.

PMID- 7723133
TI  - Patterns of resistant Salmonella typhi infection in infants.
AB  - Culture-proven cases of enteric fever (182) were studied during the period May
      1991 to April 1992; 39 per cent of the children were below 3 years. There was
      male preponderance. Infants presented within first few days of onset of fever
      with severe systemic manifestation, such as repeated convulsion, puffiness of
      face and oedema, massive hepatomegaly, and bleeds due to thrombocytopenia. Only
      49-52 per cent of the cultures were sensitive to ampicillin, chloroamphenicol,
      and cotrimoxazole. The infants were treated with cephalosporin such as cefotaxime
      or quinolones as ciprofloxacin, since 100 per cent of the cultures were sensitive
      to this drug. Three infants had meningitis, two interstitial nephritis, and six
      had marrow hypoplasia. Two children who had been treated prior to admission with
      ampicillin or chloroamphenicol died within 48 h of admission, one of a liver
      abcess and peritonitis, and the other due to meningitis. Markedly prolonged
      hypothermia was seen during recovery in few cases. Forty-six per cent of infants
      had complications as against 2 per cent in older children. Drug Resistant
      Salmonella typhi infection seems to have a rapidly progressive severe course with
      multiple organ involvement such as meningitis, liver abcess, nephritis, and
      marrow hypoplasia. Initiation of appropriate antibiotics depending on local
      sensitivity pattern is needed early in the disease to avoid mortality and
      morbidity.

PMID- 7723134
TI  - The effect of lactose maldigestion on the stools of young Tswana children.
AB  - During diarrhoeal disease, stool mass is usually increased. Lactose content of
      stools and stool pH have been used as tests for secondary lactose maldigestion.
      The effect of a lactose-free diet and various lactose loads on the stools of 30
      children with primary adult-type lactose maldigestion was investigated. Stool
      mass following the lactose tolerance test was the largest (mean = 80 g/day); that
      following the milk tolerance test less--62 g (not significantly), that on a milk
      containing diet significantly less (35 g), while stool mass produced on a lactose
      free diet (22 g) was significantly less than that produced on any of the three
      lactose-containing diets. The stool pH on a milk containing diet (mean = 6.3) was
      significantly higher than those of the three other diets (after lactose tolerance
      test, pH = 5.85; after milk tolerance test, pH = 5.86; after lactose-free diet,
      pH = 5.83). Although stool bulk was greater when these lactose maldigesters were
      consuming a lactose containing diet, it was still considerably less than the
      stool mass associated with secondary lactose maldigestion, which is believed to
      be a cause of diarrhoeal disease. In contrast, the primary adult-type of lactose
      maldigestion does not commonly cause diarrhoea, as shown in this study.

PMID- 7723135
TI  - Differential clinical and epidemiological features in children with Campylobacter
      diarrhoea, mixed-agent diarrhoea and Campylobacter diarrhoea plus parenteral
      infections.
AB  - A prospective study of 111 young Peruvian children with Campylobacter jejuni
      diarrhoea showed that it behaves as an endemic enterotoxigenic-like, waterborne,
      milkborne, and zoonotic disease. Although there were no definite differential
      features between pure C. jejuni diarrhoea, mixed-agent diarrhoea, and C. jejuni
      diarrhoea plus parenteral infections, children with C. jejuni diarrhoea plus
      parenteral infections were all inpatients, were more frequently malnourished and
      more frequently exhibited systemic symptoms. Campylobacter jejuni associated with
      other enteric pathogens did not seem to act synergistically as the disease was
      not particularly severe in this group.

PMID- 7723136
TI  - Plasma electrolyte pattern of children with protein energy malnutrition and
      children with prolonged diarrhoea.
AB  - We studied the plasma electrolyte pattern of children with prolonged diarrhoea
      and Protein Energy Malnutrition (PEM) as compared to controls to show the values
      to be expected and to determine the need for replacement therapy. Sodium,
      potassium, chloride, and bicarbonate values were found to be similar in 54
      children with clinically manifested PEM and 65 children with prolonged diarrhoea
      who had no full blown malnutrition. There were marked deficits in all the
      parameters estimated. Values were found to be statistically significant at P <
      0.001 when compared to controls.

PMID- 7723137
TI  - New diagnostic tools for tropical primary health care--the 'spectrum' mini
      centrifuge.

PMID- 7723138
TI  - Low incidence of congenital toxoplasmosis in Indian children.

PMID- 7723139
TI  - The effects of malnutrition, parental literacy and household crowding on acute
      lower respiratory infections in young Kenyan children.
AB  - This study investigated risk factors for acute lower respiratory infections
      (ALRI) in young Kenyan children. Exposures included mild-moderate malnutrition,
      household crowding, and low parental literacy. The study population consisted of
      106 toddler-aged children (18-25 months) who were free of ALRI for at least 4
      weeks before beginning a 1-year follow-up period. Subjects were visited weekly
      for morbidity information and monthly for anthropometric measurement. Being
      underweight (weight-for-age < 80 per cent of expected) was positively associated
      with ALRI, as was stunting (height-for-age < 90 per cent of expected). No
      association was found for acute wasting (weight-for-height < 90 per cent of
      expected). Having more than five siblings or parents with low reading skills were
      also risk factors. These data suggest that improving nutrition and parental
      literacy may contribute to lowering the incidence of acute lower respiratory
      infections. Interventions include breastfeeding, full immunization, diets
      adequate in quality and quantity, and early treatment through parental
      recognition of serious infections.

PMID- 7723140
TI  - Creating a basis for good outcomes.

PMID- 7723141
TI  - Putting more prevention into medical training.

PMID- 7723142
TI  - Exciting potential of DNA vaccines explored.

PMID- 7723143
TI  - From the Joint Commission on Accreditation of Healthcare Organizations.

PMID- 7723144
TI  - From the Centers for Disease Control and Prevention. Update: trends in fetal
      alcohol syndrome--United States, 1979-1993.

PMID- 7723145
TI  - From the Centers for Disease Control and Prevention. Sociodemographic and
      behavioral characteristics associated with alcohol consumption during pregnancy-
      United States, 1988.

PMID- 7723146
TI  - From the Centers for Disease Control and Prevention. Mass vaccination with oral
      poliovirus vaccine--Asia and Europe, 1995.

PMID- 7723147
TI  - Changes in Dutch opinions on active euthanasia, 1966 through 1991.

PMID- 7723148
TI  - Should physicians counsel patients to drink alcohol?

PMID- 7723149
TI  - Alcohol consumption and tissue-type plasminogen activator.

PMID- 7723150
TI  - All Vibrio cholerae infections are not created equal.

PMID- 7723151
TI  - Caffeine dependence syndrome.

PMID- 7723152
TI  - Caffeine dependence syndrome.

PMID- 7723153
TI  - Alopecia areata and presence of cytomegalovirus DNA.

PMID- 7723154
TI  - Urinary methylmalonic acid to detect vitamin B12 deficiency.

PMID- 7723155
TI  - Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for
      the Asymptomatic Carotid Atherosclerosis Study.
AB  - OBJECTIVE: To determine whether the addition of carotid endarterectomy to
      aggressive medical management can reduce the incidence of cerebral infarction in
      patients with asymptomatic carotid artery stenosis. DESIGN: Prospective,
      randomized, multicenter trial. SETTING: Thirty-nine clinical sites across the
      United States and Canada. PATIENTS: Between December 1987 and December 1993, a
      total of 1662 patients with asymptomatic carotid artery stenosis of 60% or
      greater reduction in diameter were randomized; follow-up data are available on
      1659. At baseline, recognized risk factors for stroke were similar between the
      two treatment groups. INTERVENTION: Daily aspirin administration and medical risk
      factor management for all patients; carotid endarterectomy for patients
      randomized to receive surgery. MAIN OUTCOME MEASURES: Initially, transient
      ischemic attack or cerebral infarction occurring in the distribution of the study
      artery and any transient ischemic attack, stroke, or death occurring in the
      perioperative period. In March 1993, the primary outcome measures were changed to
      cerebral infarction occurring in the distribution of the study artery or any
      stroke or death occurring in the perioperative period. RESULTS: After a median
      follow-up of 2.7 years, with 4657 patient-years of observation, the aggregate
      risk over 5 years for ipsilateral stroke and any perioperative stroke or death
      was estimated to be 5.1% for surgical patients and 11.0% for patients treated
      medically (aggregate risk reduction of 53% [95% confidence interval, 22% to
      72%]). CONCLUSION: Patients with asymptomatic carotid artery stenosis of 60% or
      greater reduction in diameter and whose general health makes them good candidates
      for elective surgery will have a reduced 5-year risk of ipsilateral stroke if
      carotid endarterectomy performed with less than 3% perioperative morbidity and
      mortality is added to aggressive management of modifiable risk factors.

PMID- 7723156
TI  - Efficacy and safety of lowering dietary intake of fat and cholesterol in children
      with elevated low-density lipoprotein cholesterol. The Dietary Intervention Study
      in Children (DISC). The Writing Group for the DISC Collaborative Research Group.
AB  - OBJECTIVE: To assess the efficacy and safety of lowering dietary intake of total
      fat, saturated fat, and cholesterol to decrease low-density lipoprotein
      cholesterol (LDL-C) levels in children. DESIGN: Six-center randomized controlled
      clinical trial. PARTICIPANTS: Prepubertal boys (n = 362) and girls (n = 301) aged
      8 to 10 years with LDL-C levels greater than or equal to the 80th and less than
      the 98th percentiles for age and sex were randomized into an intervention group
      (n = 334) and a usual care group (n = 329). INTERVENTION: Behavioral intervention
      to promote adherence to a diet providing 28% of energy from total fat, less than
      8% from saturated fat, up to 9% from polyunsaturated fat, and less than 75
      mg/4200 kJ (1000 kcal) per day of cholesterol (not to exceed 150 mg/d). MAIN
      OUTCOME MEASURES: The primary efficacy measure was the mean LDL-C level at 3
      years. Primary safety measures were mean height and serum ferritin levels at 3
      years. Secondary efficacy outcomes were mean LDL-C levels at 1 year and mean
      total cholesterol levels at 1 and 3 years. Secondary safety outcomes included red
      blood cell folate values; serum zinc, retinol, and albumin levels; serum high
      density lipoprotein cholesterol (HDL-C) values, LDL-C:HDL-C ratio, and total
      triglyceride levels; sexual maturation; and psychosocial health. RESULTS: At 3
      years, dietary total fat, saturated fat, and cholesterol levels decreased
      significantly in the intervention group compared with the usual care group (all P
      < .001). Levels of LDL-C decreased in the intervention and usual care groups by
      0.40 mmol/L (15.4 mg/dL) and 0.31 mmol/L (11.9 mg/dL), respectively. Adjusting
      for baseline level and sex and imputting values for missing data, the mean
      difference between the groups was -0.08 mmol/L (-3.23 mg/dL) (95% confidence
      interval [CI], -0.15 to -0.01 mmol/L [-5.6 to -0.5 mg/dL]), which was significant
      (P = .02). There were no significant differences between the groups in adjusted
      mean height or serum ferritin levels (P > .05) or other safety outcomes.
      CONCLUSIONS: The dietary intervention achieved modest lowering of LDL-C levels
      over 3 years while maintaining adequate growth, iron stores, nutritional
      adequacy, and psychological well-being during the critical growth period of
      adolescence.

PMID- 7723157
TI  - Temporal patterns of antihypertensive medication use among older adults, 1989
      through 1992. An effect of the major clinical trials on clinical practice?
AB  - OBJECTIVE: To describe the changing patterns of antihypertensive medication use
      in the years immediately before and after the publication of the results of three
      major clinical trials of the treatment of hypertension in older adults. DESIGN:
      In this cohort study, adults 65 years or older were examined annually on four
      occasions between June 1989 and May 1992, and the use of antihypertensive
      medications was assessed by inventory at each visit. The four visits defined the
      boundaries of three study periods. For each study period, participants receiving
      antihypertensive therapy were either continuous users (n = 1667, 1643, and 1605,
      respectively) or starters (n = 157, 142, 120) of hypertensive therapy. The large
      clinical trials that convincingly proved the efficacy and safety of low-dose
      diuretic therapy in older adults were published during the latter parts of period
      2 and the early parts of period 3. RESULTS: Among starters, the proportion
      initiating therapy on diuretics increased from 35.9% in period 2 to 47.5% in
      period 3, significantly so among women (P = .04). The proportions initiating
      other drugs displayed no significant trends. Among continuous users, the use of
      diuretics, beta-blockers, and vasodilators generally decreased over the 3-year
      period, while the use of calcium channel blockers and angiotensin-converting
      enzyme inhibitors increased significantly in each of the three periods (P < .05).
      The decline of 2.7% in the prevalence of diuretic use in period 1 abated during
      period 2 (1.8% decline), and it slowed significantly (P = .03) to almost a
      complete halt during period 3 (0.2% decline). The rate of increase in the use of
      calcium channel blockers slowed significantly (P = .01) between period 1 (+6.7%)
      and period 3 (+2.8%). CONCLUSIONS: Although other factors such as cost may have
      been important, the temporal trends in antihypertensive drug therapy coincided in
      time with and may have reflected in part the influence of the major clinical
      trials on the patterns of clinical practice.

PMID- 7723158
TI  - Transfusion requirements in critical care. A pilot study. Canadian Critical Care
      Trials Group.
AB  - OBJECTIVE: To evaluate the effects of a restrictive and a liberal red blood cell
      (RBC) transfusion strategy on mortality and morbidity in critically ill patients.
      STUDY DESIGN: Multicenter, prospective, randomized clinical trial. PATIENT
      POPULATION: Sixty-nine normovolemic critically ill patients admitted to one of
      five tertiary level intensive care units with hemoglobin values less than 90 g/L
      within 72 hours of admission. INTERVENTIONS: Patients were randomly allocated to
      one of two RBC transfusion strategies. Hemoglobin values were maintained between
      100 and 120 g/L in the liberal transfusion group and between 70 and 90 g/L in the
      restrictive group. RESULTS: Primary diagnosis and mean +/- SD age (58.6 +/- 15 vs
      59.0 +/- 21 years and Acute Physiology and Chronic Health Evaluation II score (20
      +/- 6.2 vs 21 +/- 7.2) were similar in the restrictive and liberal groups,
      respectively. Daily hemoglobin values averaged 90 g/L in the restrictive group vs
      109 g/L in the liberal group (P < .001). The restrictive group received 2.5 U per
      patient compared with 4.8 U per patient in the liberal group. This represents a
      48% relative decrease (P < .001) in RBC units transfused per patient. The 30-day
      mortality rate was 24% in the restrictive group compared with 25% in the liberal
      group; the 95% confidence interval around the absolute difference was -19% to
      21%. Similar observations were noted for intensive care unit mortality (P = .76)
      and 120-day mortality (P > .99). In addition, survival analysis comparing time
      until death in both groups did not reveal any significant difference (P = .93)
      between groups. Organ dysfunction scores were also similar (P = .44). CONCLUSION:
      In this small randomized trial, neither mortality nor the development of organ
      dysfunction was affected by the transfusion strategy, which suggests that a more
      restrictive approach to the transfusion of RBCs may be safe in critically ill
      patients. However, the study lacked power to detect small but clinically
      significant differences. Therefore, further investigations of RBC transfusion
      strategies are warranted.

PMID- 7723159
TI  - Professional boundaries in the physician-patient relationship.

PMID- 7723160
TI  - Promising new treatments for cytomegalovirus retinitis.

PMID- 7723161
TI  - Endarterectomy for asymptomatic carotid artery stenosis. Resolving the
      controversy.

PMID- 7723162
TI  - Reducing blood cholesterol levels in children. What have we learned from the DISC
      study?

PMID- 7723163
TI  - [Portal hypertension and gastric mucosa lesion--from the stand point of
      microcirculatory disturbance].

PMID- 7723164
TI  - [Study of the changes in portal hemodynamics after endoscopic injection
      sclerotherapy with reference to the variceal recurrence].
AB  - Endoscopic injection sclerotherapy (EIS) combined with percutaneous transhepatic
      obliteration was performed in 63 cirrhotic patients with esophageal varices. In
      all patients, esophageal varices were completely disappeared after EIS. To
      investigate risk factors for recurrence of esophageal varices after EIS,
      hemodynamic changes in the portal system before and after EIS were studied by
      portal vein catheterization and ultrasonography. In patients in whom portal
      pressure rose after EIS, recurrence of varices was observed in high incidence (p
      < 0.05). Furthermore, variceal recurrence appeared frequently in patients with
      progressive splenomegaly after EIS (p < 0.05). During post-EIS course, new
      appearance or increase in size of non-variceal portosystemic collaterals was
      detected by ultrasonography in 22% of the patients. In these patients, variceal
      recurrence rate was low (p = 0.09). In patients with shunts around the splenic
      hilum, variceal recurrence rate was lower compared with the patients with
      paraumbilical vein (p < 0.05). Prognostic factors for variceal recurrence were
      analysed using multiple regression model. It was suggested that the absence of
      non-variceal portosystemic collaterals was the most risky factor. In conclusion,
      observation of portal hemodynamics is considered to be useful for the long-term
      management of patients with esophageal varices treated with EIS.

PMID- 7723165
TI  - [Cell proliferation and cell death (apoptosis) in epithelial tumors of the
      stomach--analysis of tumor tissues by the endoscopic mucosal resection].
AB  - To answer the question why some gastric cancers make elevation while others make
      depression in their early stage, and why polypoid cancers grow larger than their
      benign counterpart adenomas, the distribution of proliferating cells and
      apoptotic cells was compared between these lesions. Proliferating cells and
      apoptotic cells were detected with anti Ki-67 antibody (MIB-1) and with the in
      situ nick end labeling (ISNEL), respectively. A total of 62 gastric tumors, taken
      by the endoscopic mucosal resection method, was assessed. They consisted of 14
      adenomas and 48 mucosal carcinomas (27 polypoid and 21 depressed type). Overall
      positive rates of Ki-67 were 27.5 +/- 9.0% in adenoma, 40.1 +/- 11.1% in polypoid
      cancer and 47.5 +/- 9.7% in depressed cancer. Proliferating cells were
      preferentially found in the cripts of metaplastic mucosa, in the middle to upper
      layer of adenomas, and in the whole layer including their surface of
      adenocarcinomas. Within cancers the polypoid type had more positive cells in the
      upper layer, so did the depressed type in the lower layer. ISNEL positive nuclei
      showed sphere, fragmented, ringed forms, or the same form as neighboring tumor
      nuclei. Apoptotic cells lay scattered throughout tumor glands. Apoptotic cell
      counts per 1000 tumor cells were 26.0 +/- 9.7 in adenoma, 36.3 +/- 32.1 in
      polypoid cancer, and 52.5 +/- 19.3 in depressed cancer. Depressed type cancers
      and a few polypoid cancers rich in non-tumor tissues showed higher numbers of
      apoptotic cells than adenomas and usual polypoid cancers. (ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7723166
TI  - [The development of serum alkaline phosphatase and gamma-glutamyl transpeptidase
      in early stages of primary biliary cirrhosis].
AB  - We carried out a retrospective study for the development of biochemical
      abnormalities in nine patients with early stages of primary biliary cirrhosis
      (PBC). All patients had elevated serum alkaline phosphatase (ALP) and gamma
      glutamyl transpeptidase (gamma-GTP) levels when the diagnosis of PBC was
      obtained. In all cases, serum gamma-GTP levels initially increased, followed by
      the elevation of ALP. In the routine laboratory tests gamma-GTP is more sensitive
      than ALP for the screening for early PBC.

PMID- 7723167
TI  - [A primary squamous cell carcinoma of stomach with cholecystitis and screlosing
      cholangitis caused by hepatic transarterial chemotherapy].

PMID- 7723168
TI  - [A case report of Meckel's diverticulum with axial volvulus and review of the
      literature].

PMID- 7723169
TI  - [A case of superior mesenteric vein thrombosis treated by percutaneous
      transhepatic thrombectomy].

PMID- 7723170
TI  - [A case of primary adenoid cystic carcinoma in right submandibular salivary gland
      which showed an unusual metastasis to the stomach].

PMID- 7723171
TI  - [A case of primary gastric plasmacytoma showing remarkable changes in endoscopic
      findings during five month's follow-up].

PMID- 7723172
TI  - [A case of ulcerative colitis associated with aortitis syndrome].

PMID- 7723173
TI  - [Peliosis hepatis associated with macrothrombocytosis arising in a patient with
      clinical features of systemic lupus erythematosus and rheumatoid arthritis].

PMID- 7723174
TI  - [Studies on sigma receptor in gastric acid secretion using isolated guinea pig
      parietal cells].

PMID- 7723175
TI  - [Relationship between molecular typing of Helicobacter pylori by PCR-RFLP
      analysis and specificity of disease].

PMID- 7723176
TI  - [A case of Munchausen syndrome with frequent bleeding and severe iron deficiency
      anemia].

PMID- 7723177
TI  - [Relationship between chilliness of the limbs and daily-life conditions in young
      females].
AB  - In winter, many people have trouble with chilliness in their arms and legs. Many
      women are especially sensitive to cold, and for them the chilliness of the hands
      and the feet is difficult to ease even after entering a warm room, or taking a
      bath. They even feel pain owing to coldness of their limbs in daily life. This
      symptom has been called "hiesho" in Japanese. The problem of this chilliness is
      difficult to study because this symptom, in general, can be cured when spring
      comes. Coldness of the limbs has been considered to be one of the symptoms of the
      climacteric disturbance among middle-aged females. Recently, however, it was
      reported that many young females also feel pain owing to coldness of the hands
      and legs in their daily life during winter. This study investigates the problems
      of chilliness in the limbs of young females in their daily life. By means of a
      questionnaire, 642 female college students aged from 18 to 20 years answered
      questions concerning: (1) physical characteristics, (2) physical conditions in
      their daily life, (3) physical conditions in winter, and (4) physical conditions
      in summer. The replies to the questionnaires were tested using the chi 2 test.
      The major results were as follows: 1. Half of the subjects were sensitive to
      cold, and had difficulty sleeping owing to chilliness of their limbs in winter
      even in a warm environment. For the following results the subjects who were
      sensitive to cold had significant differences (p < 0.05) compared to non
      sensitive subjects to cold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723178
TI  - [Handicaps in twins and triplets].
AB  - This study was conducted to investigate the prevalence rates of handicaps in
      twins and triplets. The subjects were 252 twins and 287 triplets. The following
      results were obtained. 1) The prevalence rates of the handicapped were 8.7 per
      100 triplets, and 4.4 per 100 twins. The risk of producing at least one
      handicapped child was approximately 22% in triplet pregnancy and 9% in twin
      pregnancy. This means that one in 4 or 5 sets of triplets had at least one
      handicapped child, as did one in 11 pairs of twins. 2) Cerebral palsy was the
      most frequent handicap in twins and triplets. The risks of producing a child with
      cerebral palsy were 2.0% and 3.1% in twins and triplets, respectively. 3) The
      prevalence rates of congenital anomalies (congenital heart disease, limb
      anomalies, and others) were 2.4% in twins and 4.5% in triplets. Approximately 45%
      of the handicaps in twins and triplets resulted from congenital anomalies. 4) The
      prevalence rate of the handicapped in twins and triplets was not associated with
      maternal age, but was associated with the years of delivery in triplets, and was
      higher in babies with shorter gestation periods.

PMID- 7723179
TI  - [Recent progress of epidemiological studies on intractable diseases in Japan].
AB  - Since 1972, the Ministry of Health and Welfare of the Japanese Government has
      been promoting researches on the etiology of and treatment for so-called
      intractable diseases of unknown causes for which no specific medical treatment is
      established. The Research Committee of the Epidemiology of Intractable Diseases
      was first organized in 1976. The committee has continuously undertaken researches
      on the epidemiology of these diseases. The paper shows examples of the results of
      the research projects of the committee. The frequency and distribution of the
      patients with intractable diseases were estimated by the statistics of patients
      receiving financial subsidies, national patient surveys and nationwide hospital
      surveys. Descriptive epidemiology of examples of the diseases are shown. Case
      control studies for selected diseases have been conducted by the Research
      Committee with the cooperation of health centers and university hospitals to
      which members of the committee belonged. A few examples are given in this report.
      Pathologists and epidemiologists are exploring the possibility of applying
      autopsy registration data to epidemiological studies. Examples of such studies
      are also given.

PMID- 7723180
TI  - [Studies on health effects of cadmium exposure in the general environment].
AB  - Effects of exposure to cadmium (Cd) in the general environment on health have
      been studied in several Cd-polluted areas in Japan. In this paper, results of
      investigations in the Kakehashi River basin, Ishikawa, a Cd-polluted area, are
      mainly reviewed as follows. 1. In an epidemiological study, prevalences of beta 2
      microglobulinuria (beta 2-MG-uria) were 14. 3 and 18.7% in Cd-exposed men and
      women over 50 years of age, respectively, when a cutoff level of beta 2-MG of
      1000 micrograms/g.cr. was used. These values are significantly high compared with
      those of nonexposed subjects. 2. Using several urinary indicators of renal
      function, such as alpha 1-microglobulin, N-acetyl-beta-D-glucosaminidase, human
      intestinal alkaline phosphatase, mucoprotein and albumin, levels of all
      indicators were significantly higher in Cd-exposed subjects than in nonexposed
      subjects. Furthermore, in a 5-year follow-up study, irreversibility of Cd-induced
      renal damage was shown after the level of beta 2-MG rose above 1000
      micrograms/g.cr. 3. Exposure to Cd caused marked osteopenia, in particular in
      women, as assessed by microdensitometry, and this osteopenia was significantly
      associated with Cd-induced renal dysfunction. Serum 1 alpha, 25 dihydroxy-vitamin
      D levels were lower and serum parathyroid hormone (PTH) levels were higher in Cd
      exposed subjects with renal damage than in nonexposed subjects. We assume that
      disturbances in vitamin D and PTH metabolism may be one of the causative factors
      for Cd-induced bone damage. 4. The dose-response relationships between Cd
      exposure and renal dysfunction were assessed using several statistical methods
      such as simple linear regression, probit linear regression, logistic regression
      analysis and general linear models. The prevalences of beta 2-MG-uria or
      metallothioneinuria were employed as indices of health effects, while urinary Cd
      and total Cd intake was used as indicators of Cd exposure. As the biological
      threshold, urinary Cd concentrations were calculated to be 3.8-4.2
      micrograms/g.cr. in men and 3.8-4.8 micrograms/g.cr. in women, and a maximum
      allowable intake of about 2 g Cd is considered to be a reasonable estimate for
      preventing Cd-induced renal dysfunction. 5. A significant association was found
      between urinary beta 2-MG and mortality in a 9-year follow-up study of 3178 Cd
      exposed inhabitants, using Cox's proportional hazards model. Moreover, mortality
      rates increased in proportion to increases in the amount of urinary beta 2-MG
      excreted. These results suggest that the prognosis for Cd-exposed subjects with
      renal tubular dysfunction is unfavorable.

PMID- 7723181
TI  - [The study of biological monitoring of inorganic arsenic exposure].
AB  - This review will describe method for biological monitoring of inorganic arsenic
      exposure, that delineates the chemical species of arsenic measured in urine. The
      studies established a method for exposure-level-dependent biological monitoring
      of inorganic arsenic exposure. Low-level exposure could be monitored only by
      determining the urinary inorganic arsenic concentration. High-level exposures
      clearly produced increased urinary inorganic arsenic, methylated arsenic (MA),
      dimethylated arsenic (DMA) and the sum of urinary inorganic arsenic and its
      metabolites (inorganic arsenic+MA+DMA) could be determined. Urinary arsenobetaine
      proved to be specifically seafood-derived arsenic, which could be distinguished
      from occupational arsenic exposure. There is increased use of gallium arsenide
      and indium arsenide in the semiconductor industry today. The determination of
      arsenic in ambient air is difficult to carry out in semiconductor factories.
      Monitoring arsenic exposure by determining the arsenic in the hair appeared to be
      of value only when used for environmental monitoring of arsenic rather than for
      biological monitoring.

PMID- 7723182
TI  - An investigation of the effects of lifestyle on care-seeking behavior using data
      from health insurance claims.
AB  - To clarify the effects of lifestyle on care-seeking behavior, we conducted a
      questionnaire survey using Morimoto's 8 lifestyle factors and tabulated the
      medical evaluations at annual medical checkup of 1212 male white-collar employees
      of a company (aged 21-60 years in 1991), and then extracted the health insurance
      data for these subjects for the first half of 1992 from the health insurance
      carrier computer system. The percentage of employees who visited medical
      facilities, the number of days of medical care, and the medical fees reported on
      the health insurance claims were chosen as indices of care-seeking behavior, and
      the relationship of each index to lifestyle and medical checkup data was
      examined. The health practice index (HPI), which was obtained by summing the
      scores for the 8 lifestyle factors was associated with the medical evaluation as
      expected, but was inversely correlated with the indices of care-seeking behavior.
      The percentage of employees who visited medical facilities, the number of the
      days of medical care, and the total medical fees were all higher for the subjects
      with high HPI scores than for those with low HPIs. Our findings are consistent
      with those of other researchers who have found an inverse relationship between
      tobacco smoking and health insurance claims, which has been attributed to the
      degree of consciousness of health. Compared to smokers, non-smokers have high
      consciousness of health and tend to consult a doctor more frequently, with
      resulting increased frequency of medical facility consultation and days of
      medical care, as well as medical fees. Lifestyle is an important aspect of
      physical and mental health status.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723183
TI  - [Effects of pepsinogen C gene polymorphisms on serum pepsinogen I and serum
      pepsinogen II levels].
AB  - Recently pepsinogens have been considered to be effective markers of terminal
      differentiation of stomach mucosa, and also good markers of preneoplastic and
      neoplastic changes of the stomach mucosa. Not a few studies concerning
      polymorphisms of pepsinogen A and C genes have been reported, however, as far as
      the authors are aware, no study was performed as to the relation between
      polymorphisms and serum pepsinogen I and II levels. Polymorphisms of the
      pepsinogen C (PGC) gene were identified by PCR, which amplifies DNA in the region
      within the intron between exon 7 and exon 8, and 6% polyacrylamide gel (no urea)
      electrophoresis. Six alleles were observed in the Japanese population.
      Frequencies for these alleles in 221 unrelated Japanese individuals were 0.077,
      0.036, 0.328, 0.240, 0.009 and 0.310, respectively. The association between the
      PGC genotype and serum pepsinogen was investigated. A higher serum pepsinogen II
      level was observed in individuals homozygous for allele 6 than in those with
      other genotypes. This result indicates that careful attention should be paid to
      the genetic background of serum pepsinogen in screening of stomach cancer by this
      method.

PMID- 7723184
TI  - [Gastroesophageal reflux and respiratory tract infection in tube-fed elderly
      patients--a comparison between scintigraphy and 24-h pH monitoring].
AB  - Aspiration pneumonia in patients who received enteral feeding via a nasogastric
      tube may result from retrograde colonization from the stomach, and this may be
      more likely when the gastroesophageal reflux is severe and the gastric pH is
      relative high. We investigated 11 elderly patients fed via nasogastric tube with
      suspected recurrent aspiration pneumonia by means of esophageal scintigraphy, 24
      h pH monitoring, gastric pH and concentrations of gram-negative bacilli in
      gastric aspirates. The grade of respiratory tract infection (RTI) was evaluated
      by the frequency of episodes of fever with respiratory symptoms. The correlation
      between the grade of RTI and reflux index by scintigraphy was statistically
      significant (p < 0.05), but the correlation between the grade of RTI and reflux
      rate by 24-h pH monitoring was not statistically significant. Although the
      correlation between gastric pH and log (base 10) concentration of gram-negative
      bacilli/ml of gastric aspirates was statistically significant (p < 0.001), the
      correlation between the grade of RTI and gastric pH was not statistically
      significant. Scintigraphy was superior for evaluation of gastroesophageal reflux
      resulting in aspiration pneumonia in the tube-fed elderly patients.

PMID- 7723185
TI  - [Experimental and clinical studies on ischemic lesions of the large intestine].
AB  - To clarify the pathogenesis and endoscopic features of ischemic lesions of the
      colon, experimental ischemia was induced in dogs by arterial ligation, gelfoam
      injection, and clipping. In addition, clinical and endoscopic features of
      ischemic lesions in ischemic colitis cases in human were studied. In the
      experimental model, arterial ligation including marginal arteries frequently
      induced erosions in the large intestine, whereas ligation of the colic artery
      alone did not induce apparent mucosal lesions of the large intestine. Gelfoam
      injection to produce thrombi into caudal mesenteric artery or middle colic artery
      induced ulcers with a high rate of incidence and frequently accompanied by
      intestinal perforation. Temporal impairment of blood supply by arterial clipping
      produced erosion, but not ulcers. A high incidence of erosion was obtained in a
      group that underwent clipping for a prolonged period and a group of receiving
      Alosenn. Mucosal blood flow measured by the hydrogen gas clearance method was
      significantly decreased at 1 hr and 4 hr after gelfoam injection compared with
      those after arterial ligation. In human cases of ischemia following arterial
      surgery, endoscopic features were similar to those lesions of the experimental
      ischemia induced by gelfoam injection. These results suggest that thrombi in
      peripheral small arteries may play a major role in the pathogenesis of ischemic
      lesions of the large intestine.

PMID- 7723186
TI  - [Effect of warm bathing on short-term and 24-hour blood pressure in bedridden
      elderly patients].
AB  - The effects of the bathing on short-term and ciracadian blood pressure (BP) in
      bedridden elderly patients were investigated in 10 bedridden patients (4 male: 6
      female) living in a community home. The mean age of the subjects was 78.7 years
      old and causes of bedridden status were cerebrovascular disease in 9 and spinal
      damage in one. To study the short-term hemodynamic effect of bathing, BP and
      pulse rate were measured every 2 minutes from 10 minutes before bathing to 14
      minutes after. Blood samples were collected before and after bathing for
      measurements of plasma catecholamine and plasma renin activity. To study the
      effect of warm bathing on circadian, BP, ambulatory BP was non-invasively
      monitored every 15 minutes for 24 hours on days with and without bathing. In the
      short-term phase, BP temporally elevated when washing the body outside the
      bathtub accompanied with a decline soaking in warm water (38 degrees C). Plasma
      catecholamine did not change after warm bathing. In the study of circadian change
      of BP, systolic BP on days of warm bathing remained at a lower level for 12 hours
      after bathing compared to days without bathing. In conclusion, hypotensive
      effects after bathing were prolonged in the bedridden elderly patients.

PMID- 7723187
TI  - [Influence of age on mouse pulmonary alveolar macrophage clonal growth].
AB  - Although monocyte influx has been suggested as the primary source of pulmonary
      alveolar macrophages (AM), increasing evidence from recent studies has indicated
      that AM may be sustained through a self-renewal mechanism. We evaluated the age
      related changes of the clonal growth (colony formation) of AM in mice (C57BL/6N
      mice and senescence accelerated mice). The colony forming unit (CFU) of AM of 24
      month old C57BL/6N mice was lower than that of AM of 4-month-old mice (p < 0.05).
      In SAMP6 (senescence accelerated mice), CFU of AM was decreased with aging (p <
      0.05). In SAMR1 (controls for SAMP6), CFU of AM was decreased with aging (p <
      0.001). In SAMR1, CFU of bone marrow (BM) adherent cells of 12-month-old mice was
      similar to that of 4-month-old mice. In SAMP6, CFU of BM adherent cells of 12
      month-old mice was larger than that of 4-month-old mice (P < 0.005). It was
      concluded that the CFU of AM declined with aging, but the CFU of the BM adherent
      cells did not. The decline of the AM CFU may be partly responsible for the defect
      of the immune response of the alveolar space in the elderly.

PMID- 7723188
TI  - [Relationship between behavioral problems and cognitive status in Alzheimer type
      and mixed Alzheimer and vascular dementia].
AB  - To investigate the relationship between troublesome behavior and cognitive status
      in Alzheimer type dementia (DAT), and to know whether the addition of
      cerebrovascular ischemia modifies that relationship, we studied behavioral and
      cognitive data from a clinical series of 57 DAT patients (mean age: 83.4 yrs) and
      31 patients with mixed Alzheimer and vascular dementia (MIX) (mean age: 83.4
      yrs). All subjects were ambulatory and were recruited from among patients having
      been admitted to our affiliated nursing home. None of them had any serious
      systemic diseases. The Dementia Behavior Disturbance scale (DBD), originally
      developed by Baumgarten et al, and the Mini-Mental State (MMS) were used for the
      evaluation of behavioral problems and cognitive status, respectively. In the DAT
      group, a significant correlation was recognized between DBD and MMS scores. In
      the MIX group, however, DBD scores did not correlate with MMS scores. Among
      patients having MMS scores greater or equal to 20, those with MIX had higher DBD
      scores (mean 19.3) than those with DAT (mean 13.7), although MMS scores in these
      two subgroups were comparable. These findings suggest that in DAT, behavioral
      problems increase in conjunction with cognitive impairments. However, with the
      addition of cerebrovascular ischemia to Alzheimer pathology, behavioral
      impairments may progress independently of cognitive decline, with more frequent
      presentation of troublesome behaviors in the early stage of dementia.

PMID- 7723189
TI  - [Trace elements analysis of serum and cerebrospinal fluid with PIXE--effect of
      age and changes in parkinsonian patients].
AB  - The concentrations of Br, Cu, Fe, Se, Zn, Mg were determined by particle-induced
      X-ray emission (PIXE) in serum and cerebrospinal fluid (CSF) of 13 untreated, 7 L
      dopa treated parkinsonian patients and 25 controls. There were significant
      positive correlations between serum concentrations and CSF concentrations of Br,
      Cu, Fe. The Cu/Zn ratio in the serum and the CSF/serum ratio of Br were
      significantly increased with age in normal controls. The mean CSF concentration
      of Mg in both treated and untreated parkinsonian patients was lower than in
      controls. PIXE is a valuable method for multielemental analysis of the serum and
      CSF.

PMID- 7723190
TI  - [Role of institutions for the elderly in senile dementia].
AB  - The purpose of this study was to assess the role of institutions for the elderly,
      and special nursing homes in particular, with regard to senile dementia. The
      subjects consisted of 81 cases who were institutionalized in our special nursing
      home from early November, 1992 to late October, 1993. Of these, 37 cases (45.7%)
      showed clinical dementia at the time of institutionalization. The severity and
      respective percentages of dementia were as follows: slight degree 32.4%, moderate
      degree 27.0% and severe degree 40.6%. The severity of dementia demonstrated
      significant correlation with age. Hasegawa's Dementia Scale, activity of daily
      living and physical conditions. The admission rate (40.5%) of the demented group
      for physical diseases was significantly higher than that (22.7%) of the non
      demented group. The majority of families of both groups first sought advice at
      institutions other than our special nursing home and the welfare office in the
      city, prior to being institutionalized. The referral rate from such institutions
      was far higher than that for direct entry from their homes. We consider that
      special nursing homes, in addition to carrying for daily living requirements,
      should pay great attention to physical diseases in patients suffering from senile
      dementia, and cooperate with medical institutes, particularly referring
      hospitals, and other welfare and health facilities, in this regard.

PMID- 7723191
TI  - [Brain MRI findings in patients with initial cerebral thrombosis and the
      relationship between incidental findings, aging and dementia].
AB  - To estimate the relationship between aging, dementia and changes observed on
      magnetic resonance imaging (MRI) seen in elderly patients with cerebral
      thrombosis, MRI findings in 103 patients with an initial stroke event (thrombosis
      group) were compared with those of 37 patients with hypertension/diabetes (high
      risk group) and 78 patients without those disorders (low risk group). In addition
      to the causative lesions in the thrombosis group, periventricular
      hyperintensities (PVH), spotty lesions (SL), silent infarctions (SI), ventricular
      dilatation (VD), and cortical atrophy (CA) were analyzed in these groups.
      Infarctions located in the internal capsule/corona radiata were the most frequent
      causative lesion. Compared to the low risk group, a high incidence of
      patchy/diffuse PVH, SI, and severe CA was seen in both the thrombosis group and
      the high risk group. Widespread PVH and multiple SL increased with age in the
      thrombosis group, while severe CA was seen in each group. SI and VD tended to
      increase after age 60, though they were not significant. Dementia, diagnosed in
      40 out of 78 patients, increased with age. Multivariate analysis revealed the
      degree of the effects of MRI findings on dementia to be marked in PVH, brain
      atrophy, causative lesions, and SL, in that order. These results indicated that
      diffuse PVH and brain atrophy, developing with age, promoted dementia in the
      elderly with vascular lesions. Moreover, they suggested that a variety of silent
      brain lesions recognized on MRI other than infarction can affect symptoms in the
      elderly.

PMID- 7723192
TI  - [A survey on elderly patients' knowledge of management of health care].
AB  - We conducted a questionnaire survey on the awareness of elderly patients in our
      hospital concerning medical management. As to the recognition of their own
      diseases, patients aged 80 or older, showed a lower degree of understanding than
      those under age 80. The proportion of patients who wished to known about their
      diagnosis decreased with age, although no statistical significance was
      recognized. Those who wished to known about their diagnosis, even if it were
      malignant, reduced significantly depending on the increase in age. In addition,
      the proportion of patients who would not like to know their diagnosis, if it were
      malignant, increased significantly as age increased. Proportions of patients who
      wanted to know other information, such as prognosis, the aims, methods and
      results of medical examination, the methods and adverse effects of treatment, and
      the names, effects and side effects of drugs, also decreased significantly as age
      increased. However, there were no statistical significant differences in the
      proportion of answers between cases of malignant and non-malignant disease. These
      data show that elderly patients had more anxiety or fear about malignancy, and
      wished to know less about medical management than non-elderly patients.

PMID- 7723193
TI  - [Parkinsonism induced or worsened by cisapride].
AB  - We report one case of parkinsonism induced by cisapride and one case of
      Parkinson's disease whose symptoms were worsened by cisapride. Case 1. A 75-year
      old female who had suffered from constipation and loss of appetite, was treated
      with cisapride for her gastro-intestinal symptoms. One year later, she developed
      progressive parkinsonian gait, cogwheel rigidity She showed parkinsonian gait,
      cogwheel rigidity and slowness in motion. Two months after cisapride was
      discontinued, her parkinsonism and depression disappeared. Case 2. A 66-year-old
      female with Parkinson's disease was given cisapride for constipation. Two months
      after starting cisapride, her akinesia and rigidity deteriorated gradually, and
      she became bed-ridden with dysphagia and dyspnea. After cisapride was
      discontinued, her parkinsonian symptoms improved gradually, and she became
      ambulant three months later. Cisapride is a benzamide derivative with a
      prokinetic action. Experimental studies have revealed that it has indirect
      cholinomimetic effects and potentially stimulates the gastrointestinal motor
      activity without blocking dopamine receptors or activating muscarinic cholinergic
      receptors. However, the present cases showed that cisapride could be a dopamine
      receptor blocker, and either induce or worsen parkinsonism. Therefore, cisapride
      should be avoided or very carefully used in parkinsonian patients and old people.

PMID- 7723194
TI  - [Fundamental and practical study for DNA analysis using tooth as a source of
      DNA].
AB  - Degree of degradation and the yield of DNA extracted from dental pulp tissues
      were examined on the tooth samples (n = 50) stored at room temperature and the
      method of DNA extraction from tooth hard tissues was also investigated. The DNA
      samples obtained were also applied to forensic odontological material examination
      including DNA fingerprinting using a probe Myo and VNTR (variable number of
      tandem repeat) analysis in D4S43 locus by PCR. The amount of DNA obtained from
      the dental pulp tissue of a single tooth varied approximately from 3 to 40
      micrograms. In most cases, high molecular weight DNA was still present in samples
      stored at room temperature for at least 336 days. When the dental pulp tissue
      samples were less than 5 mg in weight, the amount DNA extracted was usually less
      than 10 micrograms, however when the samples were more than 5 mg in weight, the
      amount of DNA extracted was more than 10 micrograms. No correlation was observed
      between the storage period of the tooth samples and the DNA extraction ratio (the
      amount of extracted DNA weight, micrograms/pulp weight, mg). The efficiency of
      DNA extraction from tooth hard tissues was investigated under different
      conditions using 0.005 M and 0.5 M EDTA solutions for decalcification. DNA was
      efficiently extracted from the tooth samples which were decalcified for one week
      without changing the 0.5 M EDTA solution or by changing the solution once within
      a week. Rapid decalcification using formic acid buffer was not suitable for DNA
      extraction from tooth hard tissues. Southern blot hybridization of DNA samples
      extracted from pulp tissues using Myo probe gave multiple bands. Finger print
      patterns obtained from DNA recovered from dental pulp and tooth hard tissues
      samples were identical, however, the number of hybridizing bands obtained from
      tooth hard tissues was less than that obtained from blood and dental pulp
      tissues. The D4S43 typing using DNA recovered from blood stains, dental pulp
      tissues and tooth hard tissues of the same individuals was in agreement with each
      other and the 184bp fragment was efficiently amplified in all the samples tested.
      The DNA obtained from dental pulp tissues usually contains high molecular weight
      DNA and was suitable for multilocus probe and PCR analysis. However, the DNA
      obtained from tooth hard tissues was suitable only for PCR analysis.

PMID- 7723195
TI  - The effects of neurotoxins 6-hydroxydopamine and 5,7-dihydroxytryptamine into the
      rat nucleus accumbens on the alcohol drinking behavior.
AB  - To elucidate the relationship between drinking behavior and brain monoamines in
      the brain rewarding system, the effects of injection of 6-hydroxydopamine (6
      OHDA) and 5,7-dihydroxytryptamine (5,7-DHT) into the rat nucleus accumbens (ACC),
      which would affect dopamine- and indoleamine-containing neurons, respectively, on
      the rat alcohol preference score were examined. The 6-OHDA (4 micrograms/side)
      treated rats showed a higher alcohol preference score for 2 weeks following the
      treatment, and a lowered dopamine (DA) level in the ACC and midbrain after ACC
      injection of 6-OHDA. On the other hand, although the serotonin (5-HT) and DA
      levels in the midbrain and 5-HT level in ACC were lowered after the injection of
      5,7-DHT, the alcohol preference score was not significantly changed in the 5,7
      DHT (4 micrograms/side)-treated rats. Taken together, these findings suggest that
      the alcohol drinking behavior is more influenced by the ACC DA activity than 5-HT
      activity. Changes in alcohol drinking behavior might be related to the
      compensatory mechanism for the rat to restore the original rewarding properties.

PMID- 7723196
TI  - [Age estimation by appearance of gray hair in pubic hair].
AB  - The pubic hair of Japanese males aged 12-90 years old (n = 123) and females 14-85
      ys. (n = 80) autopsied during 1984-1993 was investigated to determine its
      appearance age and possible appearance age of gray hair. As the appearance degree
      of gray hair in pubic hair 5 stages were applied to samples to establish a
      criterion for age estimation. Stage 0; no gray hair, 1; 1-3 gray hairs, 2; a few
      10, 3; 10 gray hairs-2/3 of the entire pubic hair, 4; more than 3/4. The
      appearance age of gray hair with appearance rate 100% (75%) was more than 65 (55)
      ys. in both sex. The possible appearance age was more than 30 ys. in males and 36
      ys. in females, practically younger than "45 years old" which had been described
      in texts. The age range with a hit rate 100% is at stage 0; less than 62 ys. in
      males, less than 59 ys. in females, at stage 1; 30-64 ys. in males, 36-60 ys. in
      females, at stage 2; 43-72 ys., 39-85 ys. and at stage 3; 49-77 ys,--.

PMID- 7723198
TI  - Death in head-down position: an autopsy report with reference to physiological
      mechanism.
AB  - A 74-year-old man was found dead in the head-down position in a hole in a pile of
      trash at his home. There was severe congestion and hemorrhage in the head and
      neck regions, and bronchial petechiae. Head-down tilt is a well-known model in
      studying the effects of weightlessness during space flight. By comparing our case
      with the physiological studies on head-down tilt, we determined that the head
      down posture would increase cardiac output, and systemic and intracranial
      pressure, while it would suppress respiration by a central or peripheral
      mechanism.

PMID- 7723197
TI  - A sandwich enzyme immunoassay for cardiac troponin I.
AB  - A sandwich enzyme immunoassay for cardiac troponin I (caTnI) is a description
      which can identify injuries to the heart. Bovine cTnI was purified from bovine
      cardiac muscle, then an antibody against cTnI was prepared. We confirmed by
      immunoblotting that the anti-cTnI antibody reacted only to proteins extracted
      from the heart and in addition, only to cTnI among them. A mouse monoclonal anti
      cTnI IgG-coated polystyrene ball was incubated with cTnI, and subsequently with
      affinity-purified rabbit anti-cTnI Fab-peroxidase conjugate. Specifically bound
      peroxidase activity was assayed by fluorometry. The detection limit was 3 fmol
      (84 ng) per assay. The cross-reaction of the sandwich enzyme immunoassay in
      regard to proteins from other organs was investigated. A little cross-reaction
      was recognizable only when proteins from skeletal muscle were in high
      concentration, but we supposed that this assay could be applied to identify
      injuries to the heart. We developed a sandwich enzyme immunoassay for bovine
      cTnI. However, further studies will be aimed at developing a sandwich enzyme
      immunoassay for human cTnI.

PMID- 7723199
TI  - [An autopsy case of traumatic subdural hematoma from arterio-venous malformation
      with diffuse axonal injury].
AB  - Diffuse axonal injury (DAI) is defined as widespread damage to axons in the white
      matter of the brain without focal injury such as contusion and acute subdural
      hematoma. A case of traumatic subdural hematoma from arterio-venous malformation
      accompanied by DAI is reported. A 58-year-old man was assaulted, and immediately
      lost consciousness, and remained unconscious during about 44 hours until his
      death. The autopsy revealed acute subdural hematoma (about 160 g) on left
      temporal lobe and left cingular, uncal and cerebellar tonsillar herniation, and
      tear and hemorrhage of the corpus callosum. Under this subdural hematoma, gray
      whitish vascular lesion with subarachnoid hemorrhage was found. Histologically,
      this lesion was diagnosed as the arterio-venous malformation. Neuropathological
      examination of the corpus callosum, dorsolateral part of midbrain and superior
      cerebellar peduncle revealed DAI findings, such as swelling and ballooning of the
      myelin fibers, swelling and waving of axons, and retraction balls. Axon
      degenerations were also observed immunohistochemically by anti-200 kD
      neurofilament antibody. From the results, his unconsciousness from the moment of
      impact might be occurred from not only subdural hematoma but also DAI.

PMID- 7723200
TI  - Suppression of graft rejection in rat keratoepithelioplasty by anterior chamber
      inoculation of donor lymphocytes.
AB  - A newly developed model of keratoepithelioplasty (KEP) in the rat was used to
      analyze the effect of anterior chamber-associated immune deviation on the
      suppression of corneal allograft rejection. The right eyes of Fisher rats
      received an anterior chamber (AC) injection of lymphocyte suspension from Dark
      Agouti (DA) rats (DAL group) or phosphate-buffered saline (positive control
      group). Seven days later, DA corneal lenticules were grafted onto both eyes of
      the recipients. Delayed type hypersensitivity (DTH) was also assessed in another
      group of Fisher rats receiving an AC injection of DA lymphocytes in the right
      eye. Within 15 days, 88% of the eyes in the positive control group demonstrated
      vigorous epithelial edema, a large area of epithelial defect, and
      vascularization. By contrast, in the DAL group, only 37% of the eyes showed
      slight epithelial edema, a small area of epithelial defect, and rare
      vascularization; suppression of graft rejection was observed in both eyes. DTH
      assay demonstrated significant suppression in the recipients of the AC injection
      of donor-type lymphocytes. This study indicates that the AC injection of donor
      type lymphocytes prior to corneal grafting suppresses allograft rejection in the
      rat KEP model, correlative with the suppression of DTH reaction.

PMID- 7723201
TI  - Expression of keratinocyte growth factor mRNA in ex vivo and in vitro specimens
      of human cornea and conjunctiva.
AB  - The expression of keratinocyte growth factor (KGF) messenger RNA (mRNA) was
      examined in both ex vivo and in vitro specimens of human skin, conjunctiva and
      cornea. Total cellular mRNA was extracted from human skin, conjunctiva, cornea,
      cultured skin fibroblasts, cultured conjunctival fibroblasts and cultured
      keratocytes. Oligo dT-primed complementary DNA (cDNA) was synthesized using each
      RNA sample as a template. Polymerase chain reaction (PCR) was used to amplify the
      DNA sequence of KGF using each cDNA sample as a template. PCR products were then
      digested with restriction enzymes in order to determine the KGF prototype. In all
      samples, PCR products of the expected size for KGF were detected. The resulting
      restriction pattern proved that these products were identical to KGF prototype I,
      ie, authentic KGF. In conclusion, human keratocytes and conjunctival fibroblasts
      express mRNA coding for KGF prototype I, ie, authentic KGF, in both ex vivo and
      in vitro specimens.

PMID- 7723202
TI  - Binding of amaranthin in photoreceptors of monkey retina.
AB  - The binding of amaranthin, specific for the Gal beta 1,3 GalNAc and NeuAc alpha
      2,3 Gal beta 1,3 GalNAc sequences, to the photoreceptors of the monkey retina was
      investigated using the avidin-biotinylated peroxidase method. Amaranthin bound to
      the surfaces of both cone and rod photoreceptors. This and previous lectin
      histochemical studies show that O-glycoside-linked glycoconjugates are present on
      the surfaces of both cones and rods: Gal beta 1,3 GalNAc and NeuAc alpha 2,3 Gal
      beta 1,3 GalNAc are the terminal sugars of the glycoconjugates around cones and
      rods, respectively.

PMID- 7723203
TI  - Maackia amurensis lectin binding in developing rat retina.
AB  - The developmental changes in the binding of Maackia amurensis lectin, specific
      for sialic acid alpha 2,3 galactose sequence, to the rat retina was investigated
      using the avidin-biotinylated peroxidase method. The lectin bound to the surfaces
      of photoreceptor outer segments from postnatal day 16 (P16), whereas it had bound
      to the other retinal layers from P14. The intense labelings of the outer segments
      were interspersed with unstained portions, which may correspond to cone
      photoreceptors. These results confirm that the sialic acid residues on the
      terminus of carbohydrate chains increase at P16 and mask the beta-galactose
      residues around rod outer segments.

PMID- 7723204
TI  - The effect of dopamine on the response to pattern stimulation--study of the chick
      ERG.
AB  - The effect of dopamine (DA) on the chick ERG was studied to evaluate its action
      on the on and off pathways and on the contrast mechanism with regard to
      background intensity. After intravitreal injection of DA, the b-wave, one
      component of the on response, was reduced with stimulus intensities lower than
      background intensity and enhanced with stimulus intensities that were higher.
      While the d-wave, one of the off responses, was enhanced with stimulus
      intensities higher than background intensity but not reduced with stimulus
      intensities that were lower. The pattern ERG amplitude was decreased at higher
      spatial frequencies. These results suggest that DA has different effects on the
      on and the off pathways as a function of the adaptive state and could affect the
      contrast mechanism.

PMID- 7723205
TI  - Surface structure of rabbit and human retina after enzymatic separation of inner
      limiting membrane.
AB  - In order to investigate the structure of the retina without the overlying inner
      limiting membrane (ILM), the ILM was separated from the retina in rabbit and
      human specimens by enzymatic digestion with matrisolve and trypsin. Human
      specimens were taken from the area between the optic disc and the fovea, while
      rabbit specimens were taken from 5 mm below the medullary ray. The rabbit
      specimens were immersed and digested in 0.05% trypsin, while the human specimens
      were immersed and digested in crude matrisolve. Digestion was carried out before
      fixation. The structure of the denuded retina without the overlying ILM was
      observed by scanning electron microscopy (SEM) following enzymatic digestion. In
      both the human and rabbit specimens, the ILM appeared to be a structure that was
      independent from the retina. The surface of the denuded retina appeared to be
      covered with Muller cell footplates, which appeared in cobblestone arrangement in
      rabbit specimens and in mosaic arrangement in human specimens. Adhesion between
      the ILM and the retina seemed to be maintained by a biochemical matrix that was
      digested by proteinases, in both rabbit and human specimens.

PMID- 7723206
TI  - Sectorial blood supply to the monkey optic disc surface from the cilioretinal
      artery.
AB  - The cilioretinal artery in one monkey eye (left) was observed using fluorescein
      videoangiography and a scanning laser ophthalmoscope, and was further evaluated
      by scanning electron microscopy after microvascular corrosion casting. Following
      intravenous injection of fluorescent dye, a choroidal flush was observed at 5.7
      seconds. Appearance of the dye in two cilioretinal arteries at the edge of the
      temporal optic disc was at 5.9 seconds, and the capillary phase of these
      arteries, at 6.4 seconds. The dye was first observed in the central retinal
      artery at 6.9 seconds. The cilioretinal arteries directly supplied the
      microcirculation of the temporal quadrant of the optic disc and the retinal
      vasculature in the disc-macular area. The vascular casting showed the entire
      course of the cilioretinal arteries in the retina. The cilioretinal arteries
      entered the temporal edge of the retrobulbar optic nerve head and branched to the
      prelaminar and the temporal edge of the optic disc.

PMID- 7723207
TI  - Immunosuppressive acidic protein in intraocular fluids.
AB  - The levels of immunosuppressive acidic protein (IAP) in the vitreous fluid or the
      aqueous humor were measured in patients with ocular diseases. Undiluted samples
      of vitreous humor were obtained during pars plana vitrectomy in patients with
      uveitis, proliferative diabetic retinopathy, and premacular fibrosis. In patients
      with intraocular tumors, vitreous samples were aspirated after enucleation.
      Aqueous humor was aspirated during cataract surgery, and levels of IAP were
      measured in patients with secondary cataract due to uveitis and senile cataract.
      Single radial immunodiffusion assay was used to quantify IAP levels. To determine
      the intraocular synthesis of IAP, we calculated the percentage of IAP in patients
      with uveitis. Patients with uveitis, tumors, and diabetic retinopathy had
      significantly higher levels of vitreous IAP than patients with premacular
      fibrosis. The percentage of vitreous IAP was higher in patients with uveitis than
      in those with tumors and diabetic retinopathy. Patients with uveitis also had
      markedly higher aqueous IAP levels than patients with senile cataract. In one
      patient with Behcet's disease, the IAP level was higher in the active stage than
      in the inactive stage. Our results suggest that immunosuppressive acidic protein
      could be produced in the eye and that it might modulate intraocular inflammatory
      processes.

PMID- 7723208
TI  - The usefulness of the Noise-Field Test as a screening method for visual field
      defects.
AB  - In 1990, we reported the usefulness of the noise-field spontaneously generated on
      a home television screen for the subjective perception of visual field defects
      (VFD) in glaucoma patients (Noise-Field Test: NFT). Recently, the sensitivity and
      specificity of the NFT for testing 555 eyes of primary open angle glaucoma
      patients and 300 eyes of subjects with normal visual field were 89.2% and 93.7%,
      respectively. We also performed a comparative study among the NFT and Tubingen
      electric campimetry (TEC) and oculokinetic perimetry (OKP), and also evaluated
      the efficiency of the NFT using participants examined in general health check-up
      systems. In the comparative study testing 136 eyes of glaucoma patients who had
      never perceived their VFD, and 114 eyes of subjects with normal visual field, the
      sensitivity of the NFT, TEC (fine), TEC (coarse), and OKP was 85.3%, 75.0%, 71.3%
      or 59.5%, respectively. The specificity was 88.6%, 78.9%, 82.5% or 95.6%,
      respectively. In the study made in the general health check-up system, the NFT
      was carried out on 935 participants (1870 eyes). After the NFT, all participants
      received an ophthalmological examination. Those participants whose fundus was
      suspected to have VFD as well as participants who reported abnormalities of the
      noise-field were examined by static perimetry. One hundred and sixty-two eyes
      perceived abnormalities of the noise-field; 58 eyes were judged as having VFD by
      an ophthalmologist and the defects were confirmed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7723209
TI  - Retinoic acid transport to lens epithelium in human aqueous humor.
AB  - Retinoids, in particular retinoic acid, are required for the normal growth and
      maintenance of many types of cells, including epithelial cells. The metabolism of
      lens epithelial cells, which are exposed to aqueous humor in the anterior
      chamber, is thought to be dependent upon aqueous humor dynamics. In human eyes
      undergoing cataract surgery, we measured retinoic acid levels using reverse-phase
      high performance liquid chromatography to investigate the possible role of
      aqueous humor in the transport of retinoic acid to lens epithelial cells. The
      retinoic acid level in the aqueous humor and the lens epithelial cells was 23.3
      +/- 2.3 pmol/ml and 1.8 +/- 0.8 pmol/micrograms protein, respectively.
      Fluorescence spectra study suggested the presence of endogenous retinoid-protein
      complexes in the aqueous humor. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis showed that the major protein in aqueous humor was albumin, a
      natural carrier protein of retinoic acid in the blood. From these results, we
      conclude that the aqueous humor may supply retinoic acid to the lens epithelial
      cells in human eyes.

PMID- 7723210
TI  - Herpetic epithelial keratitis caused by acyclovir-resistant strain.
AB  - Dendritic keratitis occurred during oral acyclovir (ACV) therapy in a 60-year-old
      man. Corneal stromal edema and iritis were found at his first visit. Herpetic
      keratouveitis was suspected, based on clinical findings and previous history.
      Treatment with steroid eyedrops and ACV ointment was initiated. However, ACV
      [corrected] ointment was changed to oral ACV, since conjunctival ulcer occurred
      as an adverse effect of the ointment. Subsequently, he received long-term oral
      ACV medication and steroid eyedrops for recurrent keratitis. The fifth recurrence
      was also treated with oral ACV and steroid eyedrops. At this time, although the
      stromal keratitis had improved, there was an outbreak of dendritic keratitis. The
      lesion healed spontaneously after only a reduction in the steroid. The 50%
      effective dose (ED)50 of the isolated virus to ACV was 4.4 +/- 0.15 micrograms/ml
      (mean +/- SD), a level considered ACV-resistant in vitro. The clinical course of
      this case emphasizes that it is important to consider the route and duration of
      ACV administration and the use of steroids in the treatment of stromal keratitis
      or keratouveitis.

PMID- 7723211
TI  - Dural sinus thrombosis in Behcet's disease--a case report.
AB  - Sinus thrombosis, which causes pseudotumor cerebri, is difficult to diagnose with
      conventional imaging apparatus, CT and MRI. We report a case of sinus thrombosis
      due to Behcet's disease diagnosed by magnetic resonance angiography (MRA). A
      forty-five-year old man with severe headache and ocular pain was examined. Since
      he had a history of oral ulcers, genital ulcers, and erythema nodosum venous
      thrombosis, he had been diagnosed as having Behcet's disease previously. He
      showed marked papilledema bilaterally but no obvious intracranial lesion was
      observed by CT and MRI. On MRA, an obstruction was apparent at the sagittal
      sinus. Anticoagulant and steroid therapy were effective to relieve the headache,
      and to improve the constricted visual field temporarily. By MRA, blood flow was
      confirmed in the sagittal sinus. However, mild papilledema persisted and finally
      vision was lost because of optic atrophy.

PMID- 7723212
TI  - Fluorescein angiographic features of neovascular maculopathy in angioid streaks.
AB  - Among the 46 eyes of 23 patients diagnosed with angioid streaks, macular
      complications (subretinal neovascularization) were found in 20 eyes of 11
      patients (43.5%): the 14 eyes of 7 males, and 6 eyes of 4 females. Of these
      patients, 81.8% were in their fifties to sixties. The patients with and without
      macular complications did not differ in the incidence of pseudoxanthoma elasticum
      and other ocular findings, including peau d'orange and salmon spots. In 17 eyes
      of 10 patients (85%) with macular complications, fluorescein angiography
      demonstrated multiple small, round, hypofluorescent dots in the area temporal to
      the macula and around the optic disc. The extent of this lesion varied from
      simple hypofluorescent dots to dots each surrounded by a hyperfluorescent area.
      These changes could be detected not by ophthalmoscopic fundus examination but
      only by fluorescein angiography.

PMID- 7723213
TI  - Retinal detachment with tear in the posterior fundus following ocular contusion.
AB  - Two unusual cases of rhegmatogenous retinal detachment following contusion to the
      eyeball showed retinal tears at the posterior fundus close to the optic disc and
      the large retinal blood vessels. In both cases, the tears were not detected
      immediately after the injury due to a coexisting vitreous hemorrhage. Both
      patients were successfully treated by pars plana vitrectomy, air-fluid exchange,
      and endolaser photocoagulation. During vitrectomies, an adhesion of the vitreous
      to the flap or the operculum of the tear was observed, with detachment of the
      remainder of the posterior vitreous from the retina. Vitrectomy allowed a more
      complete resolution of posterior tractional forces than scleral buckling, and
      eliminated the vitreous hemorrhage.

PMID- 7723214
TI  - Inhibitory effects of KW-5092, a novel gastroprokinetic agent, on the activity of
      acetylcholinesterase in guinea pig ileum.
AB  - KW-5092 ([1-[2-[[[5-(piperidinomethyl)-2- furanyl]methyl]amino]ethyl]-2
      imidazolidinylidene] propanedinitrile fumarate) is a novel gastroprokinetic agent
      with acetylcholinesterase (AChE) inhibitory activity and acetylcholine release
      facilitatory activity. The present study used guinea pig ileal homogenates to
      examine the inhibitory effects of KW-5092 on the activities of AChE and
      butyrylcholinesterase (BuChE). KW-5092 inhibited AChE and BuChE with the IC50
      values of 6.8 x 10(-8) M and 2.4 x 10(-5) M, respectively. The IC50 values of
      neostigmine for AChE and BuChE were 3.6 x 10(-8) M and 1.9 x 10(-7) M,
      respectively. HSR-803 (N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4
      dimethoxybenzamide hydrochloride), a gastroprokinetic agent, inhibited AChE and
      BuChE with the IC50 values of 8.6 x 10(-6) M and 6.0 x 10(-4) M, respectively.
      The AChE inhibition by KW-5092 was reversible and noncompetitive, whereas that by
      HSR-803 was reversible and uncompetitive. On the other hand, the AChE inhibition
      by neostigmine was non-competitive when the enzyme was preincubated with this
      inhibitor for 2 min prior to the addition of the substrate, and it was nearly
      competitive when the enzyme, the inhibitor and the substrate were incubated
      simultaneously. The present results demonstrate that KW-5092 is a selective,
      reversible and noncompetitive inhibitor of AChE with different characteristics
      from those of neostigmine and HSR-803. The AChE inhibitory action may contribute
      to its gastroprokinetic effect.

PMID- 7723215
TI  - Acceleration of healing of gastric ulcers induced in rats by liquid diet:
      importance of tissue contraction.
AB  - We examined the effect of a liquid diet or a combined diet of liquid plus
      cellulose on the healing of gastric ulcers induced in rats in comparison with
      that of solid chow. Ulcers were induced in the fundus of the stomach by luminal
      application of an acetic acid solution. The healing of ulcers could be divided
      into two phases based on the healing rate: early phase (days 1 to 10) and late
      phase (days 10 to 20). The liquid diet, but not the combined one, administered
      for 10 days significantly accelerated ulcer healing in both the early and late
      phases. The length of the ruptured muscularis mucosa decreased only in the liquid
      diet group in both phases. Regeneration of the ulcerated mucosa in the chow diet
      group was observed only in the late phase, it being markedly inhibited in the
      liquid diet group. The serum gastrin level significantly decreased in the liquid
      and combined diet groups in contrast to that in the chow group. The liquid and
      combined diets significantly reduced gastric mucosal DNA synthesis. We conclude
      that 1) the healing in this gastric ulcer model comprises two phases, and 2)
      tissue contraction is a major factor for the healing of gastric ulcers in the
      early phase, while both tissue contraction and regeneration of the ulcerated
      mucosa are involved in the healing in the late phase.

PMID- 7723216
TI  - Effect of muscarinic receptor modulators in the hypothalamic supraoptic nucleus
      of the rat.
AB  - Muscarinic antagonists were injected into the hypothalamic supraoptic nucleus
      (SON) and their effects on the acetylcholine (ACh) release of this nucleus were
      studied by in vivo microdialysis techniques. Atropine, AF-DX116 (a M2-receptor
      antagonist), 4-DAMP (a M3-receptor antagonist) and pirenzepine (a M1-receptor
      antagonist) concentration-dependently increased the ACh release. The EC50 values
      for these antagonists were 15 nM for atropine, 7.8 microM for pirenzepine, 0.39
      microM for AF-DX116 and 59 nM for 4-DAMP, suggesting the autoregulation of the
      ACh release through an activation of M2 and M3 subtypes of muscarinic receptors
      in the SON. The postsynaptic effect of muscarinic receptors on urine outflow was
      studied by microinjection of selective muscarinic receptor agonists and
      antagonists into the SON. McN-A-343 (a M1-receptor agonist) had no significant
      effect on urine outflow. Pre-microinjection of atropine, 4-DAMP, p-F-HHSiD (a M3
      receptor antagonist) or pirenzepine into the SON concentration-dependently
      attenuated the oxotremorine-induced antidiuresis. In contrast, AF-DX116 and
      methoctramine had no effect on this oxotremorine-induced action. These results
      suggest that the M3-subtype may contribute to the antidiuretic actions. Nicotine
      produced an increase in ACh release in the SON and also induced potent
      antidiuretic effects, both of which were inhibited by hexamethonium. Thus, in the
      SON, the ACh release may be autoregulated by M2- and M3-subtypes of muscarinic
      receptors and the antidiuretic effects of ACh produced through an activation of
      the M3-subtype.

PMID- 7723217
TI  - Aconitine-induced increase and decrease of acetylcholine release in the mouse
      phrenic nerve-hemidiaphragm muscle preparation.
AB  - The effect of aconitine on acetylcholine (ACh) release from motor nerve terminals
      in the mouse phrenic nerve-diaphragm muscle preparation was studied by a
      radioisotope method. Both electrical stimulation-evoked release and spontaneous
      release of 3H-ACh from the preparation preloaded with 3H-choline were measured.
      The change in the muscle tension was simultaneously recorded in the same
      preparation. Aconitine (0.1 microM) increased electrically evoked 3H-ACh release,
      while at higher concentrations (0.3-3 microM) it decreased the evoked release and
      muscle tension. High concentrations of aconitine (3-30 microM) caused a
      concentration-dependent increase in spontaneous 3H-ACh release. All these effects
      were suppressed by tetrodotoxin. The aconitine-induced spontaneous release
      consisted of two different components: a Ca(2+)-dependent phasic release that was
      inactivated within a few minutes and a Ca(2+)-independent, long lasting release
      at a low level. The depression of the Ca(2+)-dependent quantal release seems
      attributable to the decline of Ca2+ influx into the nerve rather than
      inactivation of sodium channels. We conclude that aconitine increases and then
      decreases electrical stimulation-evoked ACh release from the motor nerve through
      prolonged activation of sodium channels. Further activation of the channels
      enhances spontaneous release and the subsequent complete inactivation of the
      quantal release may be due to block of Ca2+ influx.

PMID- 7723218
TI  - Phorbol ester-induced reversible inactivation of cytotoxic T cell function:
      correlation with down-regulation of protein kinase C activity.
AB  - When an H-2d-specific cytotoxic T lymphocytes (CTL) clone, FC1, was incubated in
      the presence of 10(-7) M phorbol myristate acetate (PMA) for 10-12 hr, the
      cytolytic activity of the CTL against H-2d target cells was abrogated, but was
      reversibly restored to the normal level after subsequent incubation of the cells
      in PMA-free medium for more than 10 hr. These effects of PMA have been reported
      (Russell, J.H.: J. Immunol. 133, 907-912 (1984)), but the mode of its action has
      not been fully investigated. Here, we analyzed the biochemical basis of the PMA
      induced loss of cytolytic activity. Cycloheximide completely blocked the
      restoration of the PMA-suppressed cytolytic activity, suggesting that protein
      synthesis was required in this process. PMA-treatment did not affect the levels
      of CD3 and CD8 molecules expressed on the CTL, nor was the level of a CTL
      specific serine esterase, BLT esterase, affected by this treatment. However, the
      target cell-induced release of BLT esterase from the CTL was suppressed if the
      cells were pretreated with PMA. PMA-treatment of the CTL led to the down
      regulation of protein kinase C (PKC) activity by about 50%. On the other hand,
      staurosporin, an inhibitor of PKC, completely blocked the target cell lysis when
      added at 10(-6) M. These results suggest that the down-regulation of at least
      some isoform(s) of PKC is responsible for the PMA-induced loss of the cytotolytic
      activity of CTL.

PMID- 7723219
TI  - Antitumor effects and distribution of adriamycin incorporated into hydroxyapatite
      implants in a cancer rat model bearing swarm rat chondrosarcoma.
AB  - We investigated the antitumor effects and tissue distribution of adriamycin (ADR)
      incorporated into a hydroxyapatite (HAP) bead in a cancer rat model bearing Swarm
      rat chondrosarcoma. The Porous HAP bead (8.48 mm in diameter, 531 +/- 0.7 mg in
      weight) was used as a model bone graft. One ADR-HAP bead (ADR 0.4 mg-6.0 mg/bead)
      was implanted s.c. into a Sprague-Dawley rat at 6 days postinoculation of Swarm
      rat chondrosarcoma. ADR-HAP beads showed strong antitumor activities in a dose
      dependent manner. The dose of 6.0 mg/bead showed the highest efficacy with no
      toxic death: It caused a 98% growth inhibition on Day 31 postinoculation and a
      survival advantage of a 339% increase in life span. After the implantation of the
      ADR-HAP bead (0.4 mg/bead/body) and the i.v. administration of an equal dose of
      free adriamycin, we determined the tissue distribution of ADR for up to 90 days.
      ADR-HAP bead implanted in the tumors released ADR over a 12-week period in the
      target area. The diffusion of the drug to other organs such as the heart and
      liver was very low compared with the tumors. The area under the ADR concentration
      time curve (AUC) of the tumors was 181.6 micrograms.day/g and 5.22
      micrograms.day/g after the implantation of the ADR-HAP bead and the i.v.
      administration of free ADR, respectively. The targeting index of the tumors,
      defined as the ratio of the AUC after the implantation of the ADR-HAP bead to
      that after administration of free ADR, was 34.8.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723220
TI  - Possible involvement of androgen in increased norepinephrine synthesis in blood
      vessels of spontaneously hypertensive rats.
AB  - We investigated the effects of castration and testosterone propionate on
      sympathetic nervous systems in spontaneously hypertensive rats (SHR) and Wistar
      Kyoto rats (WKY). Four-week-old male rats were castrated. For replacement of
      androgen, testosterone propionate (500 micrograms/rat) was administered
      subcutaneously 2 times a week to castrated rats after their 14th week. The
      systolic blood pressure of the castrated SHR (44 weeks) was significantly lower
      than those of intact SHR and testosterone-replaced SHR. The norepinephrine (NE)
      levels and the tyrosine hydroxylase (TH) activities in the abdominal aorta and
      mesenteric artery of castrated SHR (45-50 weeks) were significantly lower than
      those of intact SHR. The NE levels and the TH activities in these blood vessels
      of testosterone-replaced SHR recovered to the levels obtained in those of intact
      SHR. As well as the systolic blood pressure, the NE levels and TH activities in
      blood vessels of WKY were significantly lower than those of intact SHR and showed
      no significant difference among the three groups. These results suggest that
      androgen may contribute to the development of hypertension in SHR via sustained
      enhancement of TH activity in blood vessels leading to increased NE level.

PMID- 7723221
TI  - Antidiuretic effects of ATP induced by microinjection into the hypothalamic
      supraoptic nucleus in water-loaded and ethanol-anesthetized rats.
AB  - The effects of microinjection of purinoceptor agonists into the hypothalamic
      supraoptic nucleus (SON) on urination were examined in water-loaded and ethanol
      anesthetized rats. Adenosine triphosphate (ATP), but neither adenosine
      diphosphate (ADP), adenosine monophosphate (AMP) nor adenosine, concentration
      dependently decreased the urine outflow with concomitant increase in the urine
      osmotic pressure. The ED50 value for ATP was approx. 60 nmol. The antidiuretic
      effect of ATP was blocked either by prior injection of theophylline (an
      antagonist of the P1-type purinoceptor) or by intravenous administration d(CH2)5
      D-Tyr(Et)-valine-arginine-vasopressin (VAVP). These results suggest that ATP
      injected into the SON has antidiuretic effects due to release of AVP through an
      activation of theophylline-sensitive purinoceptors.

PMID- 7723222
TI  - Enhancement by ascorbic acid 2-glucoside or repeated additions of ascorbate of
      mitogen-induced IgM and IgG productions by human peripheral blood lymphocytes.
AB  - In this study, the effect of ascorbic acid 2-glucoside (AA-2G), a stable
      derivative of ascorbic acid (AsA), or repeated additions of ascorbate on antibody
      productions by human peripheral blood lymphocytes (PBLs) was examined, and the
      physiological function of AsA was evaluated. When human PBLs were stimulated with
      Staphylococcus aureus Cowan I or pokeweed mitogen, AA-2G remarkably increased the
      numbers of IgM- and IgG-secreting cells which were detected by enzyme-linked
      immunospot assay. Although a single addition of ascorbate was without effect, the
      effect of AA-2G was remarkably inhibited by the addition of castanospermine, an
      alpha-glucosidase inhibitor; and moreover, repeated additions of AsA to the
      culture medium during the culture period enhanced the response to the same level
      as did a single addition of AA-2G. These results indicate that AsA has the
      ability to stimulate the immunoglobulin productions by AA-2G. The
      phytohemagglutinin-induced proliferative response of PBLs was also stimulated by
      AA-2G. The intracellular AsA content in PBLs cultured with AA-2G was maintained
      at relatively high levels during the culture period, whereas the content with a
      single dose of AsA reached nearly zero by the end of the experiment. These in
      vitro findings suggest that AA-2G and AsA function as potent immunostimulators of
      antibody production in humans and that the intracellular AsA content is a key
      parameter for establishing the immune response of PBLs.

PMID- 7723223
TI  - Effects of angiotensin II on isolated rabbit afferent arterioles.
AB  - We examined the effects of angiotensin II (Ang II) on isolated rabbit afferent
      arterioles to assess the direct effect of Ang II at the resistance vessel level
      in the kidney. We microdissected the superficial afferent arteriole from the
      kidney of New Zealand White rabbits. The afferent arteriole was cannulated with a
      micropipette system, and the intraluminal pressure was set at 80 mmHg. Ang II did
      not change the lumen diameter of the afferent arterioles. After the afferent
      arterioles were pretreated with aspirin DL-lysine or indomethacin, Ang II (10(-7)
      M) caused transient vasoconstriction in the afferent arterioles. Ang II (10(-7)
      M) caused persistent constriction in the afferent arterioles pretreated with NG
      nitro-L-arginine (10(-4) M). Physiological doses of Ang II decreased the lumen
      diameter of the isolated afferent arterioles pretreated with NG-nitro-L-arginine
      and aspirin DL-lysine. Dup753 (10(-6) M), an AT1-receptor antagonist, abolished
      the vasoconstrictor effects of Ang II. These findings suggest that the isolated
      rabbit afferent arteriole has AT1 receptors, and the vasoconstrictor response of
      Ang II is counteracted by vasodilatory prostaglandins and nitric oxide.

PMID- 7723224
TI  - Effects of a thromboxane A2-receptor antagonist, a thromboxane synthetase
      inhibitor and aspirin on prostaglandin I2 production in endothelium-intact and 
      injured aorta of guinea pigs.
AB  - We examined the effects of KW-3635, a thromboxane (TX) A2-receptor antagonist,
      and OKY-046, a TX synthetase inhibitor, on the prostaglandin (PG) I2 production
      in endothelium-intact and -injured guinea pig aorta and compared them with those
      of aspirin. In the endothelium-intact aorta, both the low (3 mg/kg) and the high
      (100 mg/kg) dose of aspirin similarly reduced the PGI2 production, as measured ex
      vivo 1 hr after the injury. In contrast, neither KW-3635 (10 mg/kg) nor OKY-046
      (30 mg/kg) inhibited the PGI2 production. The endothelial injury, induced by
      balloon catheterization, caused a reduction of PGI2 production in the aorta and
      decline of plasma PGI2/TXA2 ratio. In the endothelium-injured animals, the high
      dose of aspirin further reduced the PGI2 production in the aorta, whereas KW-3635
      and OKY-046 did not affect it. KW-3635 and OKY-046 also ameliorated the reduced
      ratio of PGI2/TXA2 in the plasma. The present results demonstrate that aspirin,
      but not KW-3635 or OKY-046, reduces the PGI2 production in the aorta either in
      the endothelium-intact or -injured state. It is thus suggested that the TXA2
      receptor antagonist and the TX synthetase inhibitor have some advantages over
      aspirin when used for the prevention of acute thrombosis after percutaneous
      transluminal angioplasty.

PMID- 7723225
TI  - Differences in adrenergic nerve and receptor function in dog internal thoracic,
      coronary and mesenteric arteries.
AB  - Isolated dog internal thoracic arteries (ITA) responded to norepinephrine and
      phenylephrine with concentration-related contractions, which were suppressed by
      prazosin, but not by yohimbine. Clonidine did not contract ITA. In coronary
      arterial strips, norepinephrine produced a relaxation. Isoproterenol relaxed
      coronary arterial strips contracted with serotonin but did not alter the tone of
      ITA. Forskolin and beraprost, an analog of prostaglandin I2, relaxed coronary and
      ITA strips to a similar extent. The beta-adrenoceptor density, assayed by
      [3H]dihydroalprenolol binding, was markedly less in ITA than in coronary
      arteries. Nicotine and transmural electrical stimulation did not alter the
      tension of ITA. Immunohistochemical study indicated that nerve fibers containing
      tyrosine hydroxylase immunoreactivity were markedly less in ITA than in coronary
      and mesenteric arteries. These results indicate that beta-adrenoceptor function
      and adrenergic innervation are considerably reduced in dog ITA. Norepinephrine
      induced vasocontraction appears to be mediated by alpha 1-adrenoceptors in the
      arteries.

PMID- 7723226
TI  - Postnatal changes in mRNA expression of the K+ channel in rat cardiac ventricles.
AB  - The reason for the postnatal changes of action potential duration in rat heart
      cells is still a matter of controversy. We have examined mRNA expression levels
      of Kv1.2, one of the K(+)-channel genes, in neonatal (1 week) and adult (8 weeks)
      rat cardiac ventricles. For analysis of mRNA expression, we used the reverse
      transcription-polymerase chain reaction method. The level of Kv1.2 mRNA
      expression in adult rats was significantly higher than that in neonatal rats.
      This result suggests that the levels of ion channel gene expression may be
      responsible for the postnatal changes of the action potential duration.

PMID- 7723227
TI  - IgA nephropathy.
AB  - IgAN is the most common type of glomerulonephritis worldwide, and is found more
      in men and distinctly less in blacks. It presents with macroscopic hematuria in
      about 40 to 45% of patients, with microscopic hematuria and proteinuria in about
      35 to 40%, and with nephrotic syndrome or acute renal failure in the remainder.
      The diagnosis continues to rely on the finding of the dominant or codominant
      mesangial deposition of IgA on immunohistologic examination of the kidney. No
      blood or urine test is sufficiently reliable for diagnosis. While the
      pathogenesis remains unknown, accumulating evidence suggests that polyclonal
      stimulation of immunoglobulins perhaps coupled with structural abnormalities of
      IgA play pivotal roles. These defects may account for the variety of
      autoantibodies detected in patients with both IgAN and HSP. While IgAN has an
      indolent course, about 30% of patients will reach ESRD after 20 years,
      particularly in those who present with hypertension, heavy proteinuria or renal
      insufficiency. At present, therapy is disappointing, but immunoglobulin
      supplementation and newer agents that interrupt the pathways of mesangial
      proliferation and sclerosis hold promise for the future. Kidney transplantation
      has shown excellent allograft survival.

PMID- 7723228
TI  - Targeted oncogenesis: A powerful method to derive renal cell lines.

PMID- 7723229
TI  - Cytotoxicity of mercury compounds in LLC-PK1, MDCK and human proximal tubular
      cells.
AB  - Six mercury compounds [HgCl2 (MC), Hg(CH3COO)2 (MA), Hg(NO3)2 (MN),
      C2H5HgSC6H4COONa (EMT), C6H5HgOCOCH3 (PMA) and CH3CIHg (MMC)] were studied using
      two kidney cell lines (MDCK and LLC-PK1), primary cultures of human proximal
      tubular cells (hPTC) and nonrenal cell lines (SAOS and Hep G2). Cell damage was
      measured with four different tests: neutral red uptake, mitochondrial
      dehydrogenase activity (MTT conversion), thymidine incorporation and protein
      content. Relative toxicity was established by the determination of the
      concentration of test compound inducing a 50% reduction of the parameter
      considered (EC50 value). Two groups could be distinguished: PMA, EMT and MMC are
      one order of magnitude more toxic than MC, MN and MA. Cellular uptake was
      measured by the HPLC-hybrid generation AAS after 24 hours treatment with 1.5
      microM MC, MMC, PMA or EMT in MDCK cells, revealing Hg concentrations of 42.8 +/-
      2.5 ng/mg protein for MC, 596.9 +/- 87.8 ng/mg protein for MMC, 269.8 +/- 75.7
      ng/mg protein for PMA and of 115.9 +/- 25.2 ng/mg protein for EMT. Cytotoxicity
      was positively correlated with cellular uptake. The effect of the cellular GSH
      content on the toxicity of mercury was studied using the GSH synthesis inhibitor
      L-buthionine sulfoximine (BSO). In all cases an enhanced cytotoxicity was
      observed after BSO treatment. 2-Oxo-4-thiazolidine carboxylic acid (OTC) was used
      as a substrate for the GSH synthesis. Although OTC did not enhance the GSH
      content, the cytotoxicity of MC, MN and MA decreased significantly, no changes
      were observed for the other mercurials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723230
TI  - Clusterin expression and apoptosis in tissue remodeling associated with renal
      regeneration.
AB  - To analyze the role of clusterin in renal diseases involving a regenerative
      process, we have used a novel rodent model to compare temporal and spatial
      expression of clusterin mRNA. Thus, renal artery stenosis was used to induce
      unilateral non-infarctive renal atrophy. After several weeks, when cellular
      pathology of atrophic kidneys involved minimal apoptosis or inflammatory response
      and mitosis was at normal levels, regeneration of atrophic kidneys was stimulated
      by removal of the contralateral healthy kidneys. The regrowth response was very
      rapid and involved renal hyperplasia rather than hypertrophy. Regenerating
      kidneys were studied 0, 4, 8, 24 hours and 2, 3, 5, 7, and 14 days after
      contralateral nephrectomy. Several parameters were compared: level and
      localization of clusterin mRNA; cell proliferation; cell dedifferentiation and
      redifferentiation and apoptosis. During the acute regenerative phase (first 24
      hr) clusterin expression was markedly increased, decreasing to untraceable levels
      by five days of regeneration. Clusterin mRNA was localized in dilated or
      collapsed atrophic tubules that had lost identifying surface structures of normal
      tubular epithelium (termed dedifferentiated). Clusterin was also localized in the
      periphery of some blood vessel walls. Cell proliferation peaked at three to five
      days of regeneration, and was also localized in dedifferentiated tubules. Despite
      the regenerative stimulus, an unexpected result was a transient but marked
      increase in apoptotic cell death in atrophic tubules in the first 24 hours of
      regeneration. Our results provide evidence of a temporal association between
      increased clusterin expression and apoptosis, but in situ localization showed
      clusterin mRNA over apparently viable, as well as apoptotic, cells in the
      epithelium of tubules showing clusterin expression. Clusterin mRNA was rarely
      identified over epithelial cells in foci of non-atrophic (non-dedifferentiated)
      nephrons that responded to the regenerative stimulus by cellular hypertrophy. The
      dramatic response after initiation of regeneration, especially the initiation of
      apoptosis in the tubular epithelium, may have applications for the study of
      genetic changes leading to renal oncogenesis.

PMID- 7723231
TI  - Role of receptor-associated 39/45 kD protein in active Heymann nephritis.
AB  - Active Heymann nephritis (HN) of rat, an autoimmune glomerular disease, is an
      experimental model of human membranous glomerulonephropathy (MGN), a common human
      glomerular disease. The putative autoantigen of HN is believed to be a large
      glycoprotein (gp330) present in kidneys of rat and human. Gp330 has sequence
      homology to low density lipoprotein receptor-related protein (LRP)/alpha 2
      macroglobulin receptor and co-purifies with another 45 kD protein called receptor
      associated protein (RAP) which binds to both gp330 and LRP/alpha 2-macroglobulin
      receptor. Since RAP co-purifies with gp330 and is thus present in the immunizing
      material used to induce active HN, the present study was undertaken to determine
      if gp330 or RAP individually could produce active HN and whether RAP had a role
      in the pathogenesis of active HN. Rats immunized with the traditional crude
      antigen (Fx1A) containing both gp330 and RAP developed typical HN. Although these
      rats developed low titers of autoantibody to RAP in their sera, they had no
      deposition of antibody to RAP in their kidneys. Rats immunized with gp330 also
      developed typical HN but had no autoantibody to RAP in their sera or kidneys.
      Rats immunized with RAP developed high titers of autoantibody to RAP in their
      sera but had no antibody in their kidneys and did not develop HN. Three rats were
      injected intravenously with polyclonal antibody to RAP and assessed seven days
      later for the development of passive HN. All three developed mild passive HN
      characterized by granular staining of polyclonal antibody along the capillary
      loops. CONCLUSIONS: (1) This is the first report to show that gp330 alone without
      the accompanying RAP can induce active HN; (2) RAP by itself does not induce
      active HN; (3) Autoantibodies to RAP do not appear to be involved in the
      pathogenesis of active HN induced with the traditional crude antigen, Fx1A; and
      (4) We confirm that polyclonal antibody to RAP can induce passive HN.

PMID- 7723232
TI  - Proteinuria, lipoproteins and renal apolipoprotein deposits in uninephrectomized
      female analbuminemic rats.
AB  - To elucidate the pathogenetic role of hyperlipidemia per se in the development of
      glomerulosclerosis, severely hyperlipidemic female analbuminemic rats (NAR) and
      mildly hyperlipidemic male NAR were studied for a period of 37 weeks after
      uninephrectomy (UNX). Plasma cholesterol increased from 6.3 +/- 0.4 (week 4) to
      11.9 +/- 0.6 mmol/liter (week 37) in the female NAR, and from 4.3 +/- 0.1 to 6.4
      +/- 0.5 mmol/liter in the male NAR in the same period. Plasma protein
      concentration was also consistently higher in female NAR (60 +/- 1 g/liter) as
      compared to male NAR (52 +/- 1 g/liter). Plasma viscosity was higher in female
      NAR than in male NAR, but there were no differences in blood viscosity.
      Proteinuria increased progressively in the UNX female NAR from 25 weeks after
      surgery, reaching a final value of 141 +/- 37 mg/day. No proteinuria occurred in
      the UNX male NAR (final value 15 +/- 2 mg/day). Glomerular capillary pressure,
      measured prior to the onset of proteinuria, was not significantly different in
      UNX female NAR and UNX male NAR. At the end of the study glomerulosclerosis and
      lipid deposition was only found in the UNX female NAR. Throughout the study
      hyperfiltration and hyperperfusion, relative to the one-kidney clearances of the
      sham-operated (2K) animals, were not different in UNX male and female NAR. No
      differences were observed in blood pressure. Hypertrophy, evaluated by glomerular
      diameters, was less pronounced in UNX female NAR (174 +/- 3 microns) than in UNX
      male NAR (190 +/- 7 microns). Glomerular diameters in 2K female and male NAR were
      similar (respectively 158 +/- 2 and 157 +/- 4 microns). Plasma apo B levels were
      similar (2K female NAR: 204 +/- 8 U; 2K male NAR 204 +/- 13 U), but cholesterol
      and triglyceride content of apo B-containing lipoproteins, namely VLDL, IDL and
      LDL, was increased twofold in the female NAR as compared to the male NAR,
      implying a larger particle size in the female NAR. Deposition of apo B and apo E
      was observed in the glomerular mesangium of UNX female NAR, particularly in
      sclerotic lesions. Glomerular apo A-I deposits were localized primarily in
      visceral epithelial cells and were not associated with sclerotic lesions. The
      development of proteinuria and glomerulosclerosis after UNX in female NAR but not
      in male NAR may depend upon differences in plasma lipoprotein composition, but is
      apparently not related to differences in whole kidney hyperfiltration and
      hyperperfusion, glomerular capillary pressure, or blood viscosity.

PMID- 7723233
TI  - Aggravation of rat nephrotoxic serum nephritis by anti-myeloperoxidase
      antibodies.
AB  - To investigate a possible role of anti-neutrophil cytoplasmic antibodies directed
      against myeloperoxidase (MPO-ANCA) in glomerulonephritis, we prepared anti-rat
      MPO antiserum by immunization of rat MPO into a rabbit. Then we administered anti
      rat MPO antiserum (group 1) or normal rabbit serum (NRS) (group 2) into rats
      before injection of nephrotoxic serum (NTS), which induced nephrotoxic serum
      nephritis (NTN). Other groups of rats received either anti-rat MPO anti-serum
      (group 3) or NRS (group 4) before injection of NRS but not NTS. Rats in group 1
      and group 2 were sacrificed at either 3 hours, 15 hours, or 14 days after NTS
      injection. Rats in group 3 and group 4 were sacrificed at 15 hours after the last
      NRS injection. By light microscopy, in rats with NTN sacrificed at 3 hours,
      counts of polymorphonuclear leukocytes (PMN) per glomerulus were 21.6 +/- 3.5 in
      group 1 and 8.4 +/- 1.7 in group 2 (P < 0.01). At 15 hours, massive glomerular
      fibrin deposits were observed in group 1 rats (fibrin score, 131 +/- 8), but not
      in group 2 rats (fibrin score, 27 +/- 21; P < 0.01). By direct immunofluorescence
      microscopy, rat MPO was found along glomerular capillary walls more intensely in
      group 1 rats than in group 2 rats. No pathological alterations were found in
      group 3 and group 4 rats. Further, renal elution studies revealed that eluted
      rabbit IgG contained anti-rat MPO antibodies in group 1 rats but not in group 3
      rats. These results suggest that the anti-MPO antibodies are directly involved in
      the more severe glomerular lesions in group 1 rats via interactions with MPO
      itself or activation of PMN, which release various kinds of mediators including
      MPO.

PMID- 7723234
TI  - Effect of a specific endothelin A receptor antagonist on murine lupus nephritis.
AB  - The present study was designed to assess whether a specific endothelin A (ETA)
      receptor antagonist, FR139317, affects the progression of lupus nephritis and
      affects transcription of mRNA for extracellular matrix (ECM) components,
      metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP)-1, and
      accumulation of ECM proteins in the renal cortex of NZB/W F1 mice. mRNA levels
      for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin B1 and B2
      chains, heparan sulfate proteoglycan (HSPG), MMP-1, -2, -3, and TIMP-1 increased
      significantly as nephritis progressed in NZB/W F1 mice. At 48 weeks of age, the
      levels of mRNA for alpha 1(I), alpha 1(III), alpha 1(IV) collagen chains, laminin
      B1 and B2 chains, HSPG, MMP-1, -2, -3, and TIMP-1 were increased by 5.6- (P <
      0.001), 3.6- (P < 0.01), 6.8- (P < 0.001), 5.2- (P < 0.001), 5.0- (P < 0.001),
      6.0- (P < 0.001), 7.6- (P < 0.001), 4.2- (P < 0.01), 8.2- (P < 0.001), and 15.2
      fold (P < 0.001), respectively, in the renal cortex of NZB/W F1 mice compared to
      NZW mice. Immunofluorescence microscopy showed that the accumulation of collagens
      I, III, and IV, laminin, and HSPG in the renal cortex of NZB/W F1 mice increased
      markedly with the progression of nephritis. At 20 weeks of age, NZB/W F1 and NZW
      mice were divided into two groups that received either FR139317 or its vehicle
      (saline) intraperitoneally, daily, for 28 weeks. The development of histological
      lesions, proteinuria, hypertension, accumulation of collagens I, III, and IV,
      laminin, and HSPG in the renal cortex of NZB/W F1 mice were suppressed by
      FR139317 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723235
TI  - Epidermal growth factor receptor expression is abnormal in murine polycystic
      kidney.
AB  - Renal tubular cyst formation and progressive enlargement in autosomal recessive
      polycystic kidney disease (ARPKD) are mediated by increased epithelial cell
      proliferation and altered transtubular fluid transport. Epidermal growth factor
      (EGF)-like peptides have been proposed to play roles in normal nephrogenesis and
      cystic tubular mitogenesis. Therefore, renal expression of EGF receptor (EGFR)
      protein and mRNA was examined in an animal model for ARPKD, the C57BL/6Jcpk/cpk
      (CPK) mouse. Both quantitative and qualitative abnormalities of EGFR expression
      were demonstrated. While both control and cystic proximal tubules, as well as
      control collecting tubules, demonstrated exclusive basalateral EGFR protein
      expression, cystic collecting tubules exhibited significant apical-lateral
      receptor localization. During nephrogenesis, EGFR protein expression was elevated
      in CPK renal tissue when compared to developmentally staged controls. Control and
      CPK kidneys expressed the same species of EGFR mRNA. Levels increased with
      developmental age, but were significantly higher at each stage of development in
      CPK kidneys. Overexpression of both EGFR protein and mRNA in CPK mice suggests
      altered control of EGFR protein and/or gene expression. EGFR mislocalization and
      overexpression may be mechanisms whereby the EGF-like factors in cyst fluid
      stimulate cystogenesis through an autocrine-paracrine cycle in ARPKD.

PMID- 7723236
TI  - Mechanisms of uremic inhibition of phagocyte reactive species production:
      characterization of the role of p-cresol.
AB  - It is generally recognized that the uremic syndrome results in a depression of
      immune function, but the uremic solutes responsible remain largely unidentified.
      In this study, the effect of 18 known uremic retention solutes, including urea
      and creatinine, on hexose monophosphate shunt (HMS)-dependent glucose-1-C14
      utilization (G1C-U), chemiluminescence production (CL-P) and flow cytometric
      parameters (FCP) of respiratory burst and phagocytosis were evaluated in
      granulocytes and/or monocytes. Among the compounds studied, only p-cresol
      depressed whole blood respiratory burst reactivity (G1C-U, CL-P) dose dependently
      at concentrations currently encountered in end-stage renal disease (ESRD) (P <
      0.05 from 5 micrograms/ml on). The effect of p-cresol was enhanced by increasing
      incubation times from 10 to 120 minutes. HMS activity of isolated packed
      erythrocytes remained unaffected. FCP of respiratory burst activity (Bursttest,
      expressed as log fluorescence units, LFU) revealed a marked depression in the
      presence of p-cresol (from 700 +/- 167 to 291 +/- 128 LFU for granulocytes, from
      278 +/- 102 to 146 +/- 52 LFU for monocytes, P < 0.01), whereas particle
      ingestion (Phagotest) remained unaffected. Cell-free myeloperoxidase activity was
      also markedly depressed in the presence of p-cresol. Polarity based HPLC-elution
      of a standard solution containing all the solutes studied, using a gradient from
      100% formic acid to 100% methanol during 60 minutes, revealed elution of p-cresol
      after 46.6 minutes, pointing to its relative hydrophobicity. Conjugation of p
      cresol to p-cresylsulfate anihilated the depressive effect of p-cresol on
      granulocyte function, and at the same time caused a shift in HPLC-elution pattern
      to a less lipophilic range.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723237
TI  - In vitro nephrotoxicity of Russell's viper venom.
AB  - To assess direct nephrotoxicity of Russell's viper venom (RVV; Daboia russelii
      siamensis), isolated rat kidneys were perfused in single pass for 120 min. Ten
      micrograms/ml and 100 micrograms/ml RVV were administered 60 minutes and 80
      minutes, respectively, after starting the perfusion. Furthermore, cultured
      mesangial cells and renal epithelial LLC-PK1 and MDCK cells were exposed to RVV
      (100 to 1000 micrograms/ml) for 5 minutes up to 48 hours. The IPRK dose
      dependently exhibited reductions of renal perfusate flow (RPF, 7.7 +/- 2.4 vs.
      16.5 +/- 0.7 ml/min g kidney wt in controls, experimental values given are those
      determined 10 minutes after termination of 100 micrograms/ml RVV admixture),
      glomerular filtration rate (GFR 141 +/- 23 vs. 626 +/- 72 microliters/min g
      kidney wt) and absolute reabsorption of sodium (TNa 8 +/- 1.7 vs. 79 +/- 9
      mumol/min g kidney wt), and an increased fractional excretion of sodium (FENa 60
      +/- 7 vs. 8 +/- 0.8%) and water (FEH2O 68 +/- 3.2 vs. 13 +/- 1.2%). Urinary flow
      rate (UFR) showed both oliguric and polyuric phases. Functional alterations of
      this type are consistent with ARF. Light and electron microscopy of perfusion
      fixed IPRK revealed an extensive destruction of the glomerular filter and lysis
      of vascular walls. Various degrees of epithelial injury occurred in all tubular
      segments. In cell culture studies RVV induced a complete disintegration of
      confluent mesangial cell layers, beginning at concentrations of 200
      micrograms/ml. In epithelial LLC-PK1 and MDCK cell cultures only extremely high
      doses of RVV (> 600 and 800 micrograms/ml, respectively) led to microscopically
      discernible damage. These results clearly demonstrate a direct dose dependent
      toxic effect of RVV on the IPRK, directed primarily against glomerular and
      vascular structures, and on cultured mesangial cells.

PMID- 7723238
TI  - A genetic model of malignant phase hypertension in rats.
AB  - A genetic model of malignant phase hypertension in rats is described which
      closely parallels the natural history of untreated human malignant phase
      hypertension. Although the factors initiating transition from essential
      hypertension to the accelerated phase in humans remain unknown, we report the
      characteristics of a genetically determined and reproducible phenotype which was
      found to result from a cross between hypertensive transgenic Ren-2 rats and
      normotensive Sprague-Dawley (Edinburgh) rats. Male F1 hybrids developed malignant
      phase hypertension with a penetrance of 73.5% (95% confidence limits 65.7 to
      81.3%) by 100 days of age. Phenotypic features included an accelerated rise in
      blood pressure, fibrinoid necrosis, activation of the renal renin-angiotensin
      system and microangiopathic hemolytic anemia. In an analytical cross no
      significant difference in blood pressure was observed between malignant phase and
      non-malignant phase animals prior to transition, implying that a factor in
      addition to hypertension appears necessary for inducing transition to the
      malignant phase phenotype. Segregation of the malignant phenotype suggested that
      susceptibility is determined by at most two genetic loci.

PMID- 7723239
TI  - Genetic heterogeneity in tubular hypomagnesemia-hypokalemia with hypocalcuria
      (Gitelman's syndrome).
AB  - To better clarify the genetic inheritance of primary tubular hypomagnesemia
      hypokalemia with hypocalciuria, or Gitelman's syndrome (GS), we studied eight
      families (10 patients aged 11 to 22 years; 16 parents; 9 siblings) in which at
      least one offspring had GS (plasma magnesium < 0.65 mmol/liter; plasma potassium
      < 3.6 mmol/liter; high magnesium and potassium fractional excretions; molar
      urinary calcium/creatinine < 0.10). Two families each had two offspring of
      different sex with GS, who all had tetanic episodes and/or marked weakness during
      childhood or adolescence, whereas in three other families two mothers and three
      offspring presented GS and one father and two other offspring had hypomagnesemia
      and hypocalciuria but normal plasma potassium. The mean plasma magnesium and
      potassium levels of the patients of the first two families were significantly
      lower (P < 0.05) than those of the other three families. Intralymphocytic but not
      intraerythrocytic magnesium and potassium were significantly lower (P < 0.05) in
      patients compared to controls. We hypothesize that there are two different types
      of genetic transmission of GS, one autosomal recessive and one autosomal dominant
      with high phenotype variability. It seems that this genetic heterogeneity is
      associated with a different clinical expression with frequent tetanic episodes
      and lower plasma potassium and magnesium levels in the autosomal recessive form.

PMID- 7723240
TI  - New mouse model for polycystic kidney disease with both recessive and dominant
      gene effects.
AB  - In the course of studying the genetics of chlorambucil mutagenesis, we have
      uncovered a new model for autosomal polycystic kidney disease (PKD). In the
      homozygous condition, the gene, jcpk, causes a very severe disease characterized
      by cysts in all segments of the nephron. Death usually occurs before 10 days of
      age. Extrarenal involvement was also noted; enlarged bile ducts, pancreatic
      ducts, and gall bladder often accompanied the PKD. In addition, approximately 25%
      of the aged +/jcpk heterozygotes show evidence of glomerulocystic disease. This
      gene maps to Chromosome 10 between two DNA markers, D10Mit20 and D10Mit42.
      Because this gene causes extrarenal abnormalities and because it has a
      heterozygote effect, it may be an informative animal model for the commonly
      occurring human adult dominant PKD.

PMID- 7723241
TI  - Production of interleukin-6, tumor necrosis factor alpha and interleukin-10 in
      vitro correlates with the clinical immune defect in chronic hemodialysis
      patients.
AB  - In patients with chronic renal failure alterations in monokine production are a
      common feature. Their clinical relevance has not yet been proven. We show here a
      correlation between an overproduction of interleukin-(IL)-6 and tumor necrosis
      factor alpha (TNF alpha) upon stimulation with LPS by mononuclear cells in vitro
      and the clinical grade of immunodeficiency found in these patients. Higher levels
      of IL-6 and TNF alpha were correlated with an immunocompromized state, that is,
      non-responsiveness to hepatitis B vaccination, whereas patients with a better
      immune competence showed the same levels of these cytokines as healthy controls.
      Only the patients with a good immune function showed a high secretion of IL-10.
      The feedback mechanism of IL-10 for reducing monokine synthesis seems to be
      intact in these patients. Thus the secretion of IL-10 might be regarded as a
      compensatory mechanism which controls monokine induction by chronic renal failure
      and hemodialysis treatment. Immunocompromized patients who are unresponsive to
      hepatitis B vaccination seem to be unable to enhance IL-10 synthesis for control
      of monokine overproduction. This results in higher levels of IL-6 and TNF alpha
      that might be involved in the pathogenesis of reduced immune defense.

PMID- 7723242
TI  - Plasma triglyceride levels are higher in nephrotic than in analbuminemic rats
      despite a similar increase in hepatic triglyceride secretion.
AB  - The relative contributions of increased hepatic secretion of triglyceride (TG)
      and decreased TG catabolism to hypertriglyceridemia in the nephrotic syndrome,
      and their relationship to urinary protein loss and reduced plasma colloid osmotic
      pressure (pi) remain unclear. We measured the activity of acetyl-CoA carboxylase
      (ACC) and fatty acid synthase (FAS), two key enzymes of fatty acid synthesis in
      hepatic cytosol, in fed control rats, in rats with congenital analbuminemia (NA)
      that are free of proteinuria, and in rats with adriamycin-induced nephrotic
      syndrome (ADR). Both NA and ADR rats had decreased pi (respectively 13.2 +/- 0.3
      and 10.7 +/- 0.4 mm Hg vs. control rats 18.3 +/- 0.7 mm Hg, P < 0.05), but only
      ADR rats had increased plasma TG (5.8 +/- 2.6 mmol/liter vs. 1.5 +/- 0.2
      mmol/liter in both control and NA rats, P < 0.05), and were proteinuric: 811 +/-
      45 mg/day, P < 0.01 versus control and NA rats. Total cytosolic ACC activity,
      expressed per g body weight, was increased in both NA and ADR rats by 45% and
      39%, respectively (P < 0.05). Total FAS activity was increased by 65% and 115% in
      NA and ADR rats, respectively (P < 0.05). Thus low pi was consistently associated
      with an increase in total ACC and FAS activities in the livers of fed rats.
      However, low pi was consistently associated with an increase in plasma TG only in
      ADR rats. Hepatic TG secretion rates, measured in vivo after blocking lipolysis
      with Triton WR-1339 in fasting animals, were increased by 33% in both ADR and NA
      rats as compared to controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723243
TI  - Dialysate protein losses with bleach processed polysulphone dialyzers.
AB  - We measured dialysate protein losses from polysulphone dialyzers undergoing
      repetitive processing with bleach and formaldehyde. The entire dialysate was
      collected during the first, fifth and tenth use of F-80 dialyzers. Dialysate
      protein concentration was 1.5 +/- 0.4 mg/dl N = 11 +/- SEM) during the first use,
      2.1 +/- 0.3 mg/dl during the fifth use and 3.6 +/- 0.5 mg/dl (N = 10) during the
      tenth use. In a follow-up study, dialyzers were evaluated for up to 25 uses.
      After 12 to 15 uses dialysate protein was 7.9 +/- 0.8 mg/dl (N = 13), after 16 to
      20 uses; 12.0 +/- 1.2 mg/dl (N = 13) and after 23 to 25 uses; 19.9 +/- 2.1 mg/dl
      (N = 5). Mean dialysate volume was 83.9 +/- 1.1 liters (N = 63) yielding total
      protein losses of up to 20.7 grams per treatment. Dialysate albumin losses, which
      were unmeasurable during the first use of the dialyzers, revealed a similar
      increase with reuse resulting in a mean value of 14.4 +/- 3.2 mg/dl after 23 to
      25 reuses (N = 5). Dialysate beta-2 microglobulin (beta 2m) levels were 1.05 +/-
      0.13 mg/l for dialyzers bleached < 10 times (N = 32) versus 1.54 +/- 0.15
      mg/liter for dialyzers bleached > 10 times (N = 31, P < 0.02 vs. < 10 reuses). A
      random sampling of dialyzers processed without bleach for 8, 14, 15, 24 and 25
      reuses revealed minimal protein losses, ranging from 1.4 to 2.7 mg/dl with no
      relation to reuse number and no measureable albumin.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7723244
TI  - Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of
      hypercholesterolemia alone and combined hyperlipidemia.
AB  - High levels of low-density lipoprotein cholesterol (LDL) (hypercholesterolemia)
      are commonly present in the nephrotic syndrome. Another pattern of dyslipidemia
      in nephrotic patients is an elevation of both cholesterol and triglyceride levels
      (combined hyperlipidemia). It has been postulated that the underlying cause of
      nephrotic dyslipidemia is an hepatic overproduction of apolipoprotein B (apo B)
      containing lipoproteins. To examine this hypothesis, the metabolism of LDL-apo B
      was compared between nephrotic patients with hypercholesterolemia and with
      combined hyperlipidemia. Thirteen patients (7 with hypercholesterolemia, and 6
      with combined hyperlipidemia) underwent measurements of turnover rates of
      autologous LDL apo B. The results were compared to normolipidemic controls and to
      patients with primary combined hyperlipidemia previously studied in our
      laboratory. Nephrotic patients with hypercholesterolemia generally had: (a) lower
      fractional catabolic rates of LDL apo B than normolipidemic healthy individuals;
      (b) LDL particles enriched in cholesterol; but (c) no overproduction of LDL apo
      B. In contrast, patients with combined hyperlipidemia were found to have: (a)
      high fractional catabolic rates for LDL apo B compared to normolipidemic
      controls; (b) cholesterol-poor LDL particles; and (c) markedly elevated
      production rates for LDL. Also, for the group as a whole, there was a positive
      correlation between plasma triglyceride levels and fractional catabolic rates.
      These data indicate that the metabolism of LDL is strikingly different between
      the two forms of nephrotic dyslipidemia. Although there may be common mechanisms
      contributing to LDL levels in nephrotic patients, there also appears to be a
      divergence of mechanisms depending on whether hypertriglyceridemia is associated
      with hypercholesterolemia.

PMID- 7723245
TI  - Role of IL-1 beta and prostaglandins in beta 2-microglobulin-induced bone mineral
      dissolution.
AB  - beta 2-microglobulin (beta 2m) induces an osteoclast-mediated net calcium efflux
      from neonatal mouse calvariae which occurs only after 48 hours of incubation,
      suggesting that beta 2m acts via other growth factors. To further test this
      hypothesis, calvariae were incubated with and without beta 2m in the presence of
      the prostaglandin inhibitor indomethacin, anti-interleukin-1 beta antibody (anti
      IL-1 beta), or interleukin-1 beta receptor antagonist (IL-1 beta RA). The
      addition of beta 2m to the culture medium stimulated, whereas indomethacin
      inhibited basal calcium efflux following 48 hours. However, the difference
      (delta) between the calcium efflux induced in calvariae incubated with and
      without beta 2m in basal medium and that in calvariae incubated with and without
      beta 2m in indomethacin supplemented medium was similar, suggesting a
      prostaglandin independent mechanism. There was a time dependent increase in PGE2
      in basal medium which was unaffected by beta 2m. In contrast, pre-incubating
      calvariae with either anti-IL-1 beta or IL-1 beta RA did not alter basal calcium
      efflux but completely blocked the beta 2m induced calcium efflux. Anti-IL-1 beta
      had no effect on the basal release of beta-glucuronidase but partially blocked
      the beta 2m induced release of beta-glucuronidase. Thus, the beta 2m-induced
      calcium efflux observed in neonatal mouse calvariae is dependent on interleukin-1
      beta but not prostaglandins.

PMID- 7723246
TI  - Heme protein-mediated renal injury: a protective role for 21-aminosteroids in
      vitro and in vivo.
AB  - 21-aminosteroids ("lazaroids") have recently excited much interest by virtue of
      their ability to inhibit lipid peroxidation in vitro and to protect against
      neural injury in vivo. We tested the effect of these compounds in models of heme
      protein-mediated renal injury in vitro and in vivo. We devised an in vitro model
      of heme protein-induced toxicity in which renal epithelial cells were exposed to
      heme proteins for one hour, after which they were subjected to glutathione
      depletion by 1-chloro-2,4-dinitrobenzene (CDNB). This model was associated with
      more than a threefold increase in lipid peroxidation (as measured by
      thiobarbituric acid reactive substances, TBARS) and a marked reduction in
      cellular glutathione content. In this model, 21-aminosteroids virtually prevented
      cytotoxicity as measured by the 51-chromium release assay, and significantly
      reduced TBARS in a dose-dependent manner. Catalase was partially protective in
      this model, thereby indicating hydrogen peroxide-dependent toxicity. While
      pursuing mechanisms accounting for enhanced cellular generation of hydrogen
      peroxide, we uncovered the first direct evidence that the heme prosthetic group
      per se directly stimulates cellular generation of hydrogen peroxide;
      complementing these findings is the remarkable efficacy of 21-aminosteroids in
      protecting against cytotoxicity induced by hydrogen peroxide. We also tested the
      capacity of 21-aminosteroids to protect against heme protein-mediated renal
      injury in vivo. Prior administration of 21-aminosteroids attenuated reductions in
      GFR and renal blood flow rates following the systemic infusion of methemoglobin
      in normal rats. 21-aminosteroids also attenuated renal injury observed over three
      successive days in the glycerol model of heme protein-mediated injury when this
      model was induced at a higher dose of glycerol (8 ml/kg body wt) but not at a
      lower dose (5 ml/kg body wt). We conclude that 21-aminosteroids protect against
      heme protein-mediated renal injury in vitro and in vivo. We suggest that these
      compounds are potentially useful in such clinical conditions as rhabdomyolysis,
      intravascular hemolysis and renal injury associated with hemoglobin-based red
      blood cell substitutes.

PMID- 7723247
TI  - Diffusive and convective transfer of cytokine-inducing bacterial products across
      hemodialysis membranes.
AB  - The widespread use of bicarbonate dialysate, and high-flux and high-efficiency
      dialyzers have raised concerns regarding the transmembrane passage of bacterial
      products from the dialysate into the blood compartment. To study the mechanisms
      as well as magnitude of the transmembrane transfer of bacterial products from the
      dialysate, we developed a computerized in vitro dialysis model which provides
      continuous pressure recording from the arterial, venous, dialysate inflow and
      outflow ports. By virtue of a computer controlled on-line infusion pump, this
      model permits control of ultrafiltration/backfiltration. Heparinized (10 U/ml)
      whole blood (150 ml) was circulated through the blood compartment for 120 minutes
      at 100 ml/min. Bicarbonate dialysate contaminated with Pseudomonas maltophilia
      filtrate was circulated through the dialysate compartment at 100 ml/min. A two
      point pressure of -10 mm of Hg (ultrafiltration) was maintained for the first 60
      minutes and -10 mm of Hg (backfiltration) for the next 60 minutes. Whole blood
      samples (10 ml) were drawn from the blood at 0, 60 and 120 minutes. Peripheral
      blood mononuclear cells (PBMC) harvested from these samples were incubated for 24
      hours in tissue culture medium. In addition, 0.5 ml samples of dialysate were
      collected at 0, 60 and 120 minutes and incubated with PBMC from the same donor
      for 24 hours. After 24 hour incubation, total cell-associated IL-1Ra and IL-1
      beta were measured by specific radioimmunoassay. Paired experiments were
      performed with eight high-flux synthetic membranes (polyamide) and eight low-flux
      cellulose membranes (hemophan). Cytokine production is expressed as pg/2.5
      million PBMC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723248
TI  - Dietary fatty acids and the glomerular hemodynamic response to cyclosporine in
      borderline hypertensive rats.
AB  - We have recently reported that cyclosporine A (CsA) decreases glomerular
      filtration rate in the borderline hypertensive rat (BHR), but that the glomerular
      filtration rate is normal when the rats are maintained on a diet supplemented
      with evening primrose (EP) oil. The current studies were designed to determine
      the glomerular hemodynamic changes responsible for this effect. A first group
      (PLAC-SAFF) received a diet supplemented with safflower oil (SAFF) (10% of
      calories) and placebo (PLAC). A second group (CsA-SAFF) received a diet
      supplemented with SAFF and CsA (10 mg/kg/day). A third group (CsA-EP) also
      received CsA, but the diet was supplemented with EP oil (10% of calories).
      Routine micropuncture studies were performed after five to nine weeks of
      treatment. Single nephron glomerular filtration rate (SNGFR) was lower in CsA
      SAFF than in PLAC-SAFF (36 +/- 2 vs. 46 +/- 1 nl/min, p < 0.05). Maintenance of
      SNGFR in CsA-EP compared to CsA-SAFF (48 +/- 2 nl/min vs. 36 +/- 2 nl/min, P <
      0.05) was due to higher values for single nephron plasma flow rate (156 +/- 16
      vs. 118 +/- 9off/min, P < 0.05), and higher values for the glomerular capillary
      ultrafiltration coefficient (0.091 +/- 0.013 vs. 0.054 +/- 0.010 nl/s/mm Hg, P <
      0.05). Since dietary fatty acids can affect prostaglandin (PG) production, we
      measured PGE production in isolated glomeruli. Mean values for basal production
      rates of PGE were greater in rats maintained on EP than in rats maintained on
      SAFF (3958 +/- 105 vs. 3378 +/- 146 pg PGE/mg glomerular protein, P <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723249
TI  - Long-term predictors of survival in essential mixed cryoglobulinemic
      glomerulonephritis.
AB  - We report the clinical outcome of 105 essential mixed cryoglobulinemia (EMC)
      patients with renal involvement collected throughout 25 years in three renal
      Units of Milan. The median follow-up was 72 months since renal biopsy and 131
      months since the clinical onset of EMC. Patient survival was 49% at 10 years
      after renal biopsy. Forty-two patients died primarily from cardiovascular and
      liver disease or infection, whereas 15 patients developed chronic renal failure.
      Two patients had a complete remission of the disease while 15 had a remission
      only of renal signs. Thirty-one patients are alive with persistent renal and
      extrarenal manifestations. Anti-HCV antibodies were retrospectively detected in
      34 patients and were present in 85% of them. This variable was not included in
      the statistical evaluation. At multivariate analysis, age older than 50 years,
      purpura, splenomegaly, cryocrit levels higher than 10%, C3 plasma levels lower
      than 54 mg/dl, and serum creatinine higher than 1.5 mg/dl were independent risk
      factors for death or dialysis. In conclusion, several factors may influence the
      outcome of patients with EMC nephritis. Markers of disease activity and an
      impaired renal function can herald a bad prognosis. It should be stressed,
      however, that only a minority of patients eventually develop renal failure,
      probably because in the most severe cases patients die earlier.

PMID- 7723250
TI  - A re-evaluation of the urinary parameters of acid production and excretion in
      patients with chronic renal acidosis.
AB  - We have studied acid-base balance in 32 patients attending the renal clinic of
      Mount Sinai Hospital. The parameters of acid-base balance measured included acid
      production measured as urinary sulfate and organic anions, net acid excretion
      measured as urinary ammonia plus titratable acid minus bicarbonate, and net GI
      absorption of alkali measured by a new method utilizing urinary electrolytes. Net
      GI absorption of alkali by urinary electrolytes measures alkali addition to the
      body from the GI tract as well as from any other sources, including bone. All
      patients had a creatinine clearance less than 80 ml/min and they were divided
      into two groups: those with normal serum bicarbonate (Group 1; N = 12) and those
      with subnormal serum bicarbonate (Group 2; N = 20). Hydrogen ion balance was -0.6
      +/- 9 mEq/day in the first group, while those in the second group had a hydrogen
      ion balance of +16 +/- 5 mEq/day. A group of 8 normal controls had a hydrogen ion
      balance of -0.3 +/- 5 mEq/day. When the sum of all cations was compared with the
      sum of all anions in the urine, a cation gap of exactly the same magnitude as the
      positive hydrogen ion balance was found in patients with low serum bicarbonate.
      In conclusion, our data show that patients with decreased GFR and low serum
      bicarbonate appear to have a significantly positive hydrogen ion balance.
      However, we believe that the positive hydrogen ion balance is only apparent, but
      not real for the following reasons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723251
TI  - Obstruction of proximal tubules initiates cytoresistance against hypoxic damage.
AB  - Following acute tubular necrosis (ATN), cytoresistance to further renal injury
      results. However, the initiating events and the subcellular determinants of this
      phenomenon have not been defined. Since tubular obstruction is a consequence of
      ATN, this study evaluated whether it alters tubular susceptibility to hypoxic
      damage. Extrarenal obstruction (ureteral ligation in rats) was used for this
      purpose to dissociate obstructive effects from those of ATN. Twenty-four hours
      following ureteral ligation or sham surgery, cortical proximal tubular segments
      (PTS) were isolated and subjected to hypoxic (15 or 30 min)/reoxygenation injury.
      Since oxidant stress, cell Ca2+ overload, and PLA2 attack are purported mediators
      of hypoxic/reoxygenation injury, degrees of FeS04, Ca2+ ionophore, and
      phospholipase A2-induced PTS damage also were assessed. The cell injury (% LDH
      release) which resulted from each of the above was consistently less in PTS
      obtained from obstructed kidneys. This cytoresistance: (a) did not require prior
      uremia to develop (seen with unilateral obstruction); (b) it did not appear to
      correlate with a tubular proliferative response (assessed by proliferating cell
      nuclear antigen expression); (c) it was uninfluenced by early tubular repair
      (unchanged by 24 hrs of obstruction release); and (d) it occurred without
      increased heat shock protein (HSP-70) or antioxidant enzyme (superoxide
      dismutase, catalase) expression. Total adenylate pools were higher in obstructed
      versus control PTS during injury; however, this appeared to be a correlate of the
      protection, rather than a mediator of it. In contrast, obstructed tubules
      manifested a primary increase in plasma membrane resistance to PLA2 attack
      (approximately 3-fold less lysophosphatidylcholine and free fatty acid generation
      in obstructed vs. control PTS during incubation with exogenous PLA2). In sum,
      these results indicate that: (1) tubular obstruction protects PTS from injury,
      suggesting that its development during ATN may initiate cytoresistance; and (2)
      this cytoresistance appears to be mediated, at least in part, by a direct
      increase in plasma membrane resistance to PLA2 and potentially other forms (such
      as, oxidant stress, cytosolic Ca2+ loading) of attack.

PMID- 7723252
TI  - Heat disinfection of polysulfone hemodialyzers.

PMID- 7723253
TI  - Secondary membranoproliferative glomerulonephritis.

PMID- 7723254
TI  - [Acute paraproctitis: choice of surgical treatment].
AB  - Experience in surgical treatment of more than 16 thousand patients with acute
      paraproctitis is discussed. In most cases the distal part of the main purulent
      passage comes out of the cavity of the abscess into the rectal lumen inside the
      sphincter. This makes possible in most cases simultaneous elimination of the
      inner opening of the paraproctitis in the anal canal.

PMID- 7723255
TI  - [Anaerobic paraproctitis].
AB  - The authors had 80 patients, most of them (90%) of an old age, with anaerobic
      paraproctitis. Delayed hospitalization was encountered in 62 cases, in 16 of
      these cases an erroneous diagnosis had been established. Severe concomitant
      diseases complicated the course of anaerobic paraproctitis in 80% of cases (in
      each group of three patients one had diabetes mellitus). The authors describe
      characteristic clinical manifestations and the course of various forms of
      anaerobic paraproctitis, the results of bacteriological examination, and the
      order in which the surgical treatment is applied. They suggest a scheme of drug
      therapy which is maximally approximated to cleansing of a microbial cenosis,
      including ultraviolet irradiation of the blood. All these measures allowed the
      mortality rate to be decreased from 33.3% to 17.7%.

PMID- 7723256
TI  - [Surgical treatment of colonic fistulas with descending colon].
AB  - Radical operations were conducted on 50 out of 78 patients with coloperineal and
      colovaginal fistulas consequent upon resection of the colon and bringing out its
      segments into the anal canal. The fistulas recurred in 10 patients. Individual
      choice of the operative method and development of a system of pre-, intra-, and
      postoperative special methods should reduce the incidence of recurrences after
      such operations.

PMID- 7723257
TI  - [Surgical treatment of villous tumors of the large intestine].
AB  - During a period of 10 years 487 patients were under observation, in whom 528
      glandular-villous and villous tumors of the rectum and colon were recognized.
      Malignancy was 11-12% in the colon and 26.3% in the rectum. Endoscopic removal of
      villous tumors was conducted in 78.9%, transanal excision in 6.5%, and resection
      of segments of the large intestine in 13.7% of patients. Large villous tumors of
      the large intestine must be managed by operations of a more radical character.

PMID- 7723258
TI  - [Definition, classification and combined treatment of locally invasive rectal
      neoplasms].
AB  - From analysis of 490 case records of patients with stage IV A rectal carcinoma, 3
      groups of patients were distinguished according to the size of the tumor and the
      degree of its fixation to the surrounding tissues and growth into the adjacent
      organs. Such locally spread tumors of the rectum must be subjected to combined
      treatment: preoperative large-fractional radiotherapy in concurrent local SHF
      hyperthermia followed by operation 24-48 hours later. If resectability of the
      tumor is doubtful, a relieving colostoma is formed in the first stage and
      distance gammatherapy is applied in a dose of 4 Gy twice a week to a total dose
      of 32 Gy auring medication with metronidazole and local SHF-therapy. Concurrent
      intraarterial chemotherapy with 5-fluorouracil (15 mg/kg body weight) has been
      lately introduced into practice in the treatment of such patients. The results of
      this complex treatment are evaluated 3-4 weeks after the course is completed.

PMID- 7723259
TI  - [Long-term results of formation of smooth muscle sphincter in the perineal
      colostomy area in patients after rectal extirpation].
AB  - The authors discuss an original method for formation of a smooth-muscle cuff from
      the wall of a pulled-through colon in the region of a perineal colostoma. It was
      applied in 89 patients who had undergone extirpation of the rectum for malignant
      neoplasms. The smooth-muscle sphincter was formed during removal of the rectum in
      72 patients and no earlier than 2 years after the extirpation in 17 patients.
      Inflammatory complications developed in the region of the perineal colostoa in
      the early postoperative period in 13.5% of cases. They were due to necrosis of
      the distal part of the pulled-through intestine in 3.4% of cases. There were no
      fatal outcomes. The late-term results were studied in follow-up periods of up to
      7.5 years. Satisfactory functional results were produced in 83% of the patients.
      Physiological examination showed the presence of a functioning sphincter in the
      region of the perineal colostoma.

PMID- 7723260
TI  - [Primary reconstruction of intestinal continuity in patients with complicated
      colon and rectal neoplasms].
AB  - Experience in surgical treatment of 290 patients with carcinoma of the large
      intestine following a complicated course shows that primary restoration of the
      intestinal continuity is possible. In this event, the allowable operative risk
      with consideration for the pronounced character of the pathological process must
      be analysed, and adequate anesthiological and resuscitation services must be
      provided. It is advisable that such operations are performed in specialized
      surgical institutions.

PMID- 7723262
TI  - [Surgery of the colon and rectum. (30-years of the State Scientific Center of
      Proctology of the Ministry of Health and Medical Industry of Russia)].

PMID- 7723261
TI  - [Prevention of incompetence of sigmoid-rectal anastomosis after frontal resection
      of rectum in the treatment of cancer].
AB  - Planned anterior resection of the rectum for carcinoma was conducted in 111
      patients, 38 of them underwent low resection. The formation of relieving
      transversostomy is suggested as a method for the prevention of early
      postoperative complications resulting from incompetence of the anastomosis. It
      was formed in 51.3% of cases. Besides, for preventing incompetence of
      sigmoidorectal anastomoses, connecting antimicrobial elements with kanmycin,
      dioxydin, and cephamezin were applied in 27 patients (26.2%). Incompetence of the
      anastomosis was not encountered in such cases. Complications occurred in the
      immediate postoperative period in 45 patients (40.5%), 14 of them (12.6%) had
      incompetence of the anastomosis suture. There were no fatal outcomes. The authors
      believe relieving transversostomy to be expedient mainly in low resection of the
      rectum and in patients with partial obstruction of the large intestine.

PMID- 7723263
TI  - [Transanal resection of the rectum].
AB  - A new method of an organ-preserving operation for the management of the initial
      forms of rectal carcinoma and benign tumors of the distal parts of the rectum has
      been elaborated and successfully used at the Scientific Research Institute of
      Proctology. It consists in transanal resection of the rectum with creation of a
      recto-anal anastomosis. Transanal resection of the rectum was performed on 34
      patients. Sixteen patients had giant or recurrent villous tumours of the distal
      part of the rectum 6 of which had undergone malignant degeneration. In a group of
      34 patients 14 had the initial forms of carcinoma of the inferoampular part of
      the rectum, 2 had a deep cystic colitis, and the other 2 patients were operated
      on for neurilemoma and teratoma. Recurrences were not revealed in patients with
      benign diseases in follow-up periods of 2 to 8 years. Recurrent carcinoma of the
      rectum in the region of the anastomosis was found in 2 patients in follow-up
      periods of 25 to 37 months. They underwent extirpation of the rectum. The new
      method enables stable recovery to be achieved and saves the patients from
      crippling abdomino-anal resections and extirpation of the rectum in the
      management of benign new growths and initial forms of carcinoma of the distal
      parts of this organ.

PMID- 7723264
TI  - [Reconstructive and restorative surgeries of the large intestine].
AB  - Reconstructive-restorative operations in 164 cases of colostomy are analysed. The
      colostomy was formed for injury to the large intestine in 45.7%,
      oncoproctological diseases in 35%, complications of diverticulum in 10%, and for
      other diseases (volvulus of the sigmoid colon, unspecific ulcerous colitis, etc.)
      in 9.3% of patients. The terms of the operations were chosen individually: from
      2.5-4 months after injury to 10-14 months after an oncological operation. The
      extraperitoneal method was applied in 93 and the intraperitoneal method in 71
      operations. Mortality was 2.9%.

PMID- 7723265
TI  - [Morphologic and functional aspects in the treatment of patients with intestinal
      fistulas].
AB  - Combination of severe purulent processes (peritonitis, phlegmons, and extensive
      wounds of the abdominal wall), eventration, and complete high unformed intestinal
      fistulas leads to rapid hemostasis disorders and emaciation. In nonoperative
      treatment lethality reaches 70%. Complete bilateral disconnection of the fistula
      bearing intestinal loop is the operation of choice in such situations. In this
      case the length of the disconnected intestinal segments may be two thirds of the
      length of the jejunum and the greater part of the colon. The results of
      morphofunctional study of an intestinal segment disconnected for a long period
      are analysed. The tactics of active surgical treatment is illustrated by clinical
      cases.

PMID- 7723266
TI  - [Polymer materials in laparostomy of peritonitis].
AB  - Cleansing of the abdominal cavity by the open method-laparostomy and the use of
      polymer materials-was conducted in 85 patients with generalized peritonitis
      (mainly due to perforation of a malignant tumor of the colon). With the use of
      this method the incidence of purulent complications reduced from 50% to 35.2% and
      mortality from 42% to 25.8%.

PMID- 7723267
TI  - [Preparation of the large intestine for the surgical treatment of intestinal
      obstruction].
AB  - Obstruction of the large intestine of tumorous origin was treated by the
      traditional methods in 191 patients: an emergency operation in peritonitis or
      nonoperative management of the obstruction by cleansing enema, purgatives, and
      infusion-transfusion therapy. In another group of 341 patients emergency
      colonoscopy and ultrasonic diagnosis were resorted to and the "obstruction index"
      (Deltz et al. 1989) was used for objectification of the indications for an
      emergency operation. The method of fractional oral treatment with 30% solution of
      polyethelyne oxide-400 and 1% chloramphenicol was applied in this group.
      Traditional treatment caused resolution of the obstruction in 22.8% of patients
      in the control and in 28.3% of patients in the experimental group. Postoperative
      mortality was 24.1% and 16.4%, respectively. The obstruction index allowed
      correct evaluation of the indications for operation in 97% of cases, the number
      of forced operation reduced from 52.2% to 14.1%.

PMID- 7723268
TI  - [Orthograde intestinal lavage in the preparation for colonoscopy].
AB  - Thirty-eight proctological patients were prepared for colonoscopy by drinking 2l
      of aqueous solution of polyethylene glycol-4000 and electrolytes, so that
      additional purgatives, cleansing enemas, and waste-free diet are not needed.
      Control of hemodynamics, clinical and biochemical blood tests, and plasma
      electrolyte content revealed no significant changes in these parameters after
      preparation for the examination. Colonoscopy was conducted to a full measure in
      94% of cases. This method was preferred rather than the use of purgatives and
      enemas by 82% of patients. Intestinal lavage with polyethylene glycol and
      electrolyte solution is a simple and effective method, it is convenient for the
      patient and does not cause marked side effects.

PMID- 7723269
TI  - [Therapeutic use of external intestinal stomas].

PMID- 7723270
TI  - [Muscle grafts in the reconstructive surgery of rectal sphincter].
AB  - Analysis of experimental (146 operations) and clinical (14 patients) material
      provides the grounds for recommending plastics with muscles on a mobile
      neurovascular pedicle to be included in the complex of surgical rehabilitation of
      patients with incompetence of the sphincter ani muscles. Optimization of the
      functional results of such operations holds much promise for the use of the
      method of muscular plastics on a mobile neurovascular pedicle in proctology.

PMID- 7723271
TI  - [Management of patients after reconstructive and restorative surgery of the large
      intestine].
AB  - Reconstructive-restorative operations were conducted on the large intestine in
      932 patients. Means of optimization of treatment in the early postoperative
      period in elderly and old-aged patients, who often have concomitant diseases,
      must be searched for. The dynamics of energy consumption in the early
      postoperative period was studied in 15 patients. Considerable effectiveness of
      complex diet including proteins was established during elaboration of individual
      dosed feeding. The immune status was studied in dynamics in 38 patients;
      immunomodulation agents lead in most cases to restoration of the reduced immunity
      indices or have a stabilizing effect on them when used both as a preventive and
      as a therapeutic measure. Percutaneous electrostimulation in the early
      postoperative period proved to be highly effective in arresting the pain
      syndrome, removal of functional intestinal paresis and reflex ischuria.

PMID- 7723272
TI  - [Diagnosis and treatment of inflammatory infiltrates of the abdominal cavity in
      Crohn disease].
AB  - An infiltrate in the abdominal cavity in Crohn's disease does not hinder
      successful drug therapy in most cases. A positive effect (regression or a marked
      decrease in the size of the infiltrate) is achieved in 80% of patients, mostly in
      those with a moderately or mildly severe form of the disease in which a
      sufficiently prolonged, 10-12-week course of antiinflammatory treatment can be
      conducted. Combination of prednisolone with azathioprine and antibiotics is most
      justified. The prednisolone dose is determined by the severity and activity of
      the disease rather than by the infiltrate. Antibiotics are necessary only in high
      fever and treatment with them may be limited to 10-14 days in the absence of
      septicemia. Interrupted seasonal courses of sulfasalazine therapy may fail to
      prevent exacerbation and, consequently, recurrent infiltrates. These respond
      readily to repeated drug therapy and do not expand the indications for surgery.
      Operations were performed on 14 patients, in 11 of them the infiltrate did not
      recur again.

PMID- 7723273
TI  - [Treatment of hemorrhoids].

PMID- 7723274
TI  - [30 years of proctological services of Russian Federation].

PMID- 7723275
TI  - Progress in pancreatic cancer: implications of phenotypic and molecular
      plasticity.

PMID- 7723276
TI  - Adhesion molecules in renal diseases.

PMID- 7723277
TI  - New pancreas cancers cell lines that represent distinct stages of ductal
      differentiation.
AB  - BACKGROUND: Most available pancreas cancer cell lines have been in culture for
      long periods of time, have not been extensively characterized from the cell
      biology standpoint, or lack differentiated properties. EXPERIMENTAL DESIGN: We
      have established four new cell lines from ductal pancreatic cancers (IMIM-PC-1,
      IMIM-PC-2, SK-PC-1, and SK-PC-3). The phenotype and functional properties of the
      cell lines were analyzed using ultrastructural methods, antibodies detecting
      cytokeratin polypeptides and mucin epitopes, and cDNA probes of epithelial
      differentiation markers. RESULTS: IMIM-PC-2 and SK-PC-1 cells grow as a polarized
      monolayer, form domes, and express all CK polypeptides typical of simple
      epithelia and the MUC1 mucin. IMIM-PC-1 and SK-PC-3 are morphologically less
      differentiated and express low or undetectable levels of CK7 and MUC1. By
      Northern blotting, we found that SK-PC-1 and SK-PC-3 cells express carbonic
      anhydrase II and that the cystic fibrosis transmembrane regulator was
      undetectable in the four lines. Secretin induces a marked stimulation of cAMP
      levels in all cell lines except for SK-PC-3. Cytogenetic analysis demonstrates
      their human origin. CONCLUSIONS: Levels of CK7 and MUC1 are associated with less
      differentiated cultures. The new cell lines should be useful tools to study the
      cell biology of exocrine pancreas cancer.

PMID- 7723278
TI  - Karyotype findings and molecular analysis of the bcr gene rearrangement
      supplementing the histologic classification of chronic myeloproliferative
      disorders.
AB  - BACKGROUND: Histologic examination of bone marrow is important in establishing
      diagnoses among chronic myeloproliferative disorders (CMPD). Only a few studies,
      however, have compared cytogenetic or molecular genetic findings to
      histopathology in CMPD. Diverging results on the presence of the Ph1
      translocation in patients with myelofibrosis have been reported. EXPERIMENTAL
      DESIGN: Cytogenetic studies and molecular analysis of the bcr gene were performed
      in bone marrow cells of patients with CMPD simultaneously with histopathologic
      examination of plastic-embedded bone marrow biopsies. RESULTS: The Ph1-chromosome
      was found in 120/128 (93%) cases with histopathologic diagnosis of chronic
      myeloid leukemia (CML), including a notable proportion of cases with an increase
      of megakaryocytes and/or myelofibrosis; the latter was associated with a
      significant increase of chromosome aberrations, in addition to Ph1. Among those
      additional changes in myelofibrosis of Ph1-positive CML were del (13q) and
      t(1;11) in one case each. A bcr gene rearrangement was detected in 92% (24/26) of
      the CML cases examined. All other groups of CMPD, comprising cases of
      myelofibrosis and unclassifiable cases, were Ph1-negative by both cytogenetics (n
      = 102) and molecular analysis (n = 18). Karyotype changes associated with
      myelofibrosis in various CMPD concerned mainly balanced translocations involving
      1p36 and 11q11, deletions of 5q13-34, 3p, 11q23, 13(q12,q22), and 20q12 as well
      as gain of 1q and trisomy 3, 8, 19, or 21. In histologically unclassifiable CMPD,
      karyotyping provided additional information for the differential diagnosis.
      CONCLUSIONS: The correlation of cytogenetic findings and histopathologic features
      is helpful in confirming or supporting histopathologic diagnoses and in
      characterizing new marker chromosomes in CMPD.

PMID- 7723279
TI  - Semiquantitative polymerase chain reaction for t(14;18) in follicular lymphomas:
      a colorimetric approach.
AB  - BACKGROUND: Autologous bone marrow transplantation is increasingly being used in
      the management of several types of cancer, and to avoid reintroduction of
      malignant cells, bone marrow purging is often performed. In such cases, sensitive
      quantitation methods are needed both to assess the efficacy of the purging and
      for surveillance of patients in remission. Polymerase chain reaction (PCR) has
      the necessary sensitivity for this application, but it requires that the cancer
      cells can be recognized by a defined genetic abnormality. In addition, PCR is in
      principle a qualitative technique and must be modified for quantitative purposes.
      In follicular non-Hodgkin's lymphomas, the translocation t(14;18) (q32;q21) is
      common and is used here for model experiments. EXPERIMENTAL DESIGN: A PCR-based
      method for the quantitation of translocation-positive cells was developed on the
      basis of coamplification of cancer-specific target molecules with competitor
      molecules of known concentration. Gel electrophoresis was substituted by a
      colorimetric quantitation system to cope with patient PCR products of the same
      size as the competitor product and ease automation of the method at a later
      stage. Cell line Karpas 422, which contains the t(14;18) (q32;21) translocation,
      was used to validate the method. The method was used to assess the efficacy of a
      patient bone marrow purging where the initial infiltration levels were too low
      for traditional detection systems. RESULTS: A reproducible and near linear
      response was obtained between 70 pg and 200 ng K422 DNA, equivalent to 10 K422
      cells and 30,000 K422 cells, respectively. Bone marrow infiltration in one
      patient was 0.6 to 0.7% before malignant cell removal and 3 to 7 x 10(-4) after
      removal. The corresponding figures for the other patient were 2% and 3 to 7 x 10(
      4), respectively. CONCLUSIONS: The method presented has a sufficient dynamic
      range for applications like evaluation of bone marrow purging or monitoring of
      minimal residual disease. Adaptation of this method to other translocations is
      discussed.

PMID- 7723280
TI  - Numerical sex chromosomal abnormalities in pineal teratomas by cytogenetic
      analysis and fluorescence in situ hybridization.
AB  - BACKGROUND: Central nervous system teratomas are a rare subgroup of extragonadal
      germ cell tumors. Previous studies show ovarian mature teratomas to be
      karyotypically normal; those with increasing immaturity show increasing
      cytogenetic abnormalities. Adult testicular teratomas, regardless of maturity,
      most often show the i sochromosome 12p, a consistent chromosomal abnormality seen
      in adult testicular germ cell tumors. This study investigates the cytogenetic
      abnormalities of six central nervous system teratomas by the use of routine
      karyotypic analysis and fluorescence in situ hybridization. EXPERIMENTAL DESIGN:
      Karyotypic analysis was performed on two tumors. Four additional tumors were
      analyzed by dual-labeled fluorescence in situ hybridization. Paraffin blocks were
      disaggregated, and nuclei were hybridized with both biotin- and digoxigenin
      labeled probes to the centromeric domains of the X and Y chromosomes,
      respectively. Tumor cells were scored for X and Y copy number. Tumor ploidy was
      determined by image analysis of the disaggregated specimens. RESULTS: The
      patients (five male, one female) ranged from 2 to 25 years of age. All presented
      with a solitary mass in the suprasellar region. A mature teratoma was 48, XXYY;
      an immature teratoma was 47, XXY, dir dup 11 (q12-22). Lymphocyte analysis of the
      second patient showed a normal constitutional karyotype. Fluorescence in situ
      hybridization analysis of four additional patients showed both one mature and one
      immature teratoma from male hosts to have 2X and 1Y signals in the majority of
      the cells. An immature teratoma from a male host showed 2X and 2Y signals. The
      above three tumors were diploid by static image analysis. An immature teratoma
      from a female host showed multiple (four to six) X signals in more than 70% of
      the cells. Ploidy analysis was unavailable for this case. CONCLUSIONS: Although
      patients with Klinefelter syndrome (47,XXY) and patients with 46,XY gonadal
      dysgenesis show an increased incidence of germ cell tumors, numerical sex
      chromosomal abnormalities have not been described in extragonadal teratomas. Our
      results support a role for sex chromosomes in the development of central nervous
      system teratomas.

PMID- 7723281
TI  - Overlapping expression of immunohistochemical markers and synaptophysin mRNA in
      pheochromocytomas and adrenocortical carcinomas. Implications for the
      differential diagnosis of adrenal gland tumors.
AB  - BACKGROUND: The differential diagnosis of cortical versus medullary tumors of the
      adrenal gland may be a problem in diagnostic pathology. Conflicting results have
      been reported about the distribution of various immunohistochemical markers in
      the normal as well as neoplastic adrenal cortex and medulla. EXPERIMENTAL DESIGN:
      Archival, formaldehyde-fixed, and paraffin-embedded material comprising 27
      adrenocortical carcinomas (ACC, meeting Weiss' histologic criteria), 28
      pheochromocytomas (PCC), and adjacent nontumorous tissue (13 glands) were
      analyzed by immunogold-silver staining for the expression of polysialic acid
      (poly Sia), cytokeratins (CK), synaptophysin (SYN), chromogranin A (CrgA),
      somatostatin (SOM), calcitonin (CT), and the "adrenocortical marker" D11.
      Further, SYN mRNA expression was studied by nonradioactive in situ hybridization
      using digoxigenin-labeled oligonucleotide probes. RESULTS: In the normal adrenal
      gland, poly Sia was exclusively detected in the medulla and in cortical nerves.
      In ACCs, SYN immunoreactivity was present in 23 of 27 tumors (85%), D11 was
      present in 22 of 27 (81%), poly Sia was present focally in 8 of 27 (29%), and CK
      was present in 7 of 27 (25%). Synthesis of SYN in ACCS was demonstrated by mRNA
      in situ hybridization. Immunoreactivity for CrgA, SOM, or CT was not detectable.
      No difference of the marker profiles was seen in the nine clinically hormone
      producing (three androgen, five corticosteroid, one mineralocorticoid) ACCs
      compared with the clinically silent tumors. In PCCs, all 28 tumors were
      immunoreactive for poly Sia and SYN; CrgA was detectable in 26 of 28 (93%), CT
      was detectable in 6 of 28 (21%), and SOM was detectable in 2 of 28 (7%) tumors.
      Staining for D11 or CK was undetectable. By immunohistochemistry, no distinction
      was possible between the 4 clinically malignant, the 6 multiple endocrine
      neoplasia type 2A-associated, and the 18 sporadic benign PCCs. CONCLUSIONS: Poly
      Sia of the neural cell adhesion molecule is consistently detected in normal
      adrenal medullary cells as well as in PCCs, and is occasionally focally expressed
      in ACCs. CrgA, CK, and D11 are reliable markers to immunohistochemically
      distinguish ACC from PCC. Immunoreactivity for SYN and detection of its mRNA in
      the majority of ACCs indicates the existence of tumor cells sharing both cortical
      and medullary features. Such focal neuroendocrine differentiation in ACCs can
      lead to confusion with PCCs.

PMID- 7723282
TI  - DNA ploidy, proliferative index, and epidermal growth factor receptor: expression
      and prognosis in patients with gastric cancers.
AB  - BACKGROUND: The 5-year survival rate of patients with stomach cancer is usually
      around 20%. The clinico-pathological features that are presently used to assess
      patient prognosis are not sufficient to define gastric tumor behavior. Therefore,
      an accurate analysis of different biological characteristics of gastric cancer
      cells could allow the course of disease to be predicted and may help to improve
      treatment strategies. EXPERIMENTAL DESIGN: The prognostic values of DNA ploidy,
      proliferative activity and epidermal growth factor receptor (EGF-R) expression
      were studied in gastric tumors from a series of 63 patients. DNA ploidy and
      proliferative activity, evaluated in terms of DNA index (DI) and proliferative
      index (PI), respectively, were determined by flow cytometry on paraffin-embedded
      tumor tissues. EGF-R expression was detected by immunohistochemistry on paraffin
      embedded tumor sections of the same specimens. The clinico-pathological and the
      biological parameters were then correlated, and the patients overall survival was
      calculated using a chi-square test and the Kaplan-Meier method. RESULTS: DNA
      ploidy abnormal cell clones were found in 44% of cases (median DI = 1.4, range
      1.04-2.5). Aneuploid tumors showed high PI more frequently than diploids (71%
      versus 36%, p = 0.01). The analysis of the expression of EGF-R revealed that 88%
      of aneuploid tumors were positive for receptor expression. On the contrary,
      diploid tumors showed the presence of EGF-R only in 56% of cases (p = 0.01). DI,
      PI, and EGF-R expression were not related to histological grade. Conversely, the
      three biological parameters were significantly correlated to clinical stage and
      tumor invasion. The Kaplan-Meier survival curves showed a 73% 5-year survival
      rate in patients with diploid tumors whereas only 33% of patients with aneuploid
      lesions had a good prognosis (p = 0.001). CONCLUSIONS: We demonstrate that DNA
      ploidy, PI, and EGF-R expression are closely related to some pathological and
      clinical characteristics in gastric cancer. The close relationship between
      aneuploidy, EGF-R positive expression, node involvement, and tumor invasion
      suggests that these parameters may be indicators of high malignancy. Finally, the
      results also show that aneuploidy and EGF-R-positive expression are indicative of
      a worse prognosis in gastric cancer patients. The study of these parameters might
      allow a more accurate stratification of patients, so that a targeted therapeutic
      protocol may be defined.

PMID- 7723283
TI  - Retinal vascular endothelial cell endocytosis increases in early diabetes.
AB  - BACKGROUND: Several physiological studies in recent years have convincingly
      demonstrated increased clearance of intravascular protein tracers by several
      different tissues, including the retina, during early diabetes and galactosemia
      in the rat. This change has been described as a consequence of increased
      permeation, although vascular leakage has not been demonstrated, and the fate of
      such tracers remains unelucidated. EXPERIMENTAL DESIGN: A pilot study in this
      laboratory showed no evidence of vascular leakage but suggested increased
      endocytosis of horseradish peroxidase (HRP) by retinal vascular endothelial cells
      (RVECs) in early diabetes. We therefore quantified RVEC endocytosis in normal,
      streptozotocin (STZ)-treated nondiabetic and STZ-diabetic rats using the design
      based stereology method of "vertical sections." A duration of diabetes (6 weeks)
      was chosen to approximate the time period in which other workers have
      demonstrated increased protein permeation of the retina. RESULTS: After a 20
      minute exposure to the tracer, HRP reaction product was observed in small
      vesicular and tubular endosomes and larger multivesicular bodies of the RVECs.
      Stereological analysis revealed a 6.5-fold increase in the volume of HRP
      containing organelles in the RVECs of diabetic rats compared with STZ-treated
      nondiabetics or normal controls. None of the animals in this study showed HRP
      reaction product outside the retinal vascular endothelium. CONCLUSIONS: A highly
      significant increase in RVEC endocytosis occurs in early diabetes. Increased RVEC
      endocytosis may contribute to the observed clearance of intravascular protein
      tracers by the retina during early diabetes.

PMID- 7723284
TI  - Expression of membrane glycoconjugates on sheep lung endothelium.
AB  - BACKGROUND: Carbohydrates play an important role in both the regulation and
      expression of endothelial cell surface molecules. EXPERIMENTAL DESIGN: To
      investigate the molecular phenotype of endothelial cells in the sheep lung, we
      used a panel of 39 lectins and carefully titrated lectin histochemistry to
      identify small vessel glycoconjugates. Expression of glycoconjugates on isolated
      cells was studied by flow cytometry and lectin Western blotting. RESULTS: Eight
      lectins stained small vessel endothelium with minimal background staining. To
      confirm cell surface binding, endothelial cells from the peripheral lung were
      isolated and tested for lectin recognition by flow cytometry. Three lectins
      (Datura stramonium, Griffonia simplicifolia-1, Lycopersicon esculentum) also
      stained isolated lung cells by flow cytometry. A lectin Western transfer
      technique demonstrated common binding to a high molecular weight (100 to 130 kD)
      band. CONCLUSIONS: The use of lectins as probes of cell surface carbohydrate
      expression supports the possibility of selective glycoconjugate expression on
      sheep endothelium.

PMID- 7723285
TI  - Human corneal basement membrane heterogeneity: topographical differences in the
      expression of type IV collagen and laminin isoforms.
AB  - BACKGROUND: The corneal epithelium converges at the peripheral zone (limbus) with
      the conjunctival epithelium, forming a continuous sheet with phenotypically
      distinct regions--central, limbal, and conjunctival. The epithelial basement
      membrane (EBM) is important for corneal functions and cell adhesion, but its
      regional composition is poorly understood. Current literature is controversial as
      to the occurrence of type IV collagen in the cornea. The aim of this study was to
      investigate in detail corneal basement membrane (BM) composition and correlate it
      with the differentiation state of contributing cells. EXPERIMENTAL DESIGN: Adult
      human corneas (N = 8) were cryosectioned and analyzed by immunofluorescence with
      antibodies to 15 BM components and to keratin 3, a marker of corneal epithelial
      differentiation. RESULTS: A novel type of spatial heterogeneity ("horizontal") in
      the EBM composition was found between the central cornea, limbus, and
      conjunctiva. Central EBM had type IV collagen alpha 3-alpha 5 chains, whereas
      limbal and conjunctival EBM contained alpha 1-alpha 2 chains and also laminin
      alpha 2 and beta 2 chains. Limbal EBM in addition had alpha 5(IV) chain. Laminin
      1 (alpha 1 beta 1 gamma 1), laminin-5 (alpha 3 beta 3 gamma 2), perlecan,
      fibronectin, entactin/nidogen, and type VII collagen were seen in the entire EBM.
      Another novel type of BM heterogeneity ("vertical") was typical for the corneal
      Descemet's membrane: its stromal face had alpha 1(IV) and alpha 2(IV) chains and
      fibronectin, whereas alpha 3(IV)-alpha 5(IV) chains, entactin/nidogen, laminin-1,
      and perlecan were present on the endothelial face. CONCLUSIONS: Type IV collagen
      controversy is the result of the shifts of isoforms in the limbus and
      conjunctiva. These shifts and the appearance of additional laminins in the limbus
      may be related to the differentiation state of corneal cells contributing to the
      EBM formation. Novel types of BM heterogeneity in the human cornea are described:
      regional (horizontal) in the EBM and vertical in the Descemet's membrane. The
      first one may be a common feature of converging complex epithelia, whereas the
      second one may be another unique property of the Descemet's membrane.

PMID- 7723287
TI  - Immunofluorescence quantitation of stromelysin in human synovial fibroblasts by
      confocal laser scanning microscopy.
AB  - BACKGROUND: Elevated levels of stromelysin have been reported in humans with
      osteoarthritis and rheumatoid arthritis, as well as in animal models of
      arthritis. However, a considerable amount of heterogeneity is observed in the
      expression of this enzyme in pathologic tissues as well as in in vitro systems.
      To analyze this variability, stromelysin expression was quantitated in individual
      human synovial fibroblasts (HSF) obtained from osteoarthritis patients.
      EXPERIMENTAL DESIGN: HSF were incubated with interleukin-1 (40 units/ml), an
      agonist known to induce stromelysin, in the presence or absence of dexamethasone
      (0.01 to 100 nM), an inhibitor of stromelysin transcription. With a stromelysin
      specific antibody and a tetramethyl-rhodamine 5-isothiocyanate-labeled secondary
      antibody, the enzyme was visualized and the fluorescence in individual cells was
      quantified with an ACAS 570 laser cytometer in confocal mode. RESULTS:
      Stromelysin expression varied from one cell to another; however, on the basis of
      the magnitude of expression of stromelysin by each cell, the "nonresponders"
      within each treatment were identified. Approximately 34% of the cells showed a
      higher level of stromelysin expression in IL-1-treated HSF compared with
      controls. A dose-dependent inhibition in the expression of stromelysin was
      observed in response to increasing concentrations of dexamethasone. The dose
      dependent changes in the accumulation of stromelysin protein correlated well with
      the stromelysin mRNA expression. CONCLUSIONS: Confocal laser scanning microscopy
      can be effectively used to analyze cellular heterogeneity in stromelysin
      expression.

PMID- 7723286
TI  - Acquired resistance to acute oxidative stress. Possible role of heme oxygenase
      and ferritin.
AB  - BACKGROUND: Prior administration of endotoxin has conferred resistance to tissue
      damage in a number of models of organ injury. The mechanisms by which this
      resistance is conferred are enigmatic. Recognizing that enhanced tissue oxidative
      stress may be a feature of endotoxin-associated injury and is present in many
      models of tissue injury, we questioned whether the beneficial effect conferred by
      endotoxin is dependent on the up-regulation of antioxidant defenses. EXPERIMENTAL
      DESIGN: We employed the glycerol model of acute renal failure (Gly-ARF), a model
      in which oxidant damage occurs in the kidney and other organs as a result of
      rhabdomyolysis and hemolysis. Rats were pretreated with endotoxin 24 hours
      before, or at the time of, induction of Gly-ARF. Renal functional studies and
      assessment of renal antioxidant status were performed. The effect of prior
      treatment with endotoxin was also examined in models of methemoglobin-induced and
      ischemic ARF. RESULTS: Renal function was improved in rats pretreated with
      endotoxin but worsened in rats subjected to Gly-ARF and endotoxin simultaneously.
      Endotoxin induced heme oxygenase activity and ferritin content in the kidney but
      did not induce other antioxidant systems such as catalase and glutathione
      peroxidase. Treatment with a competitive inhibitor of heme oxygenase blocked
      endotoxin-induced protection on days 2 and 3, while markedly attenuating the
      protective effect on day 1. Pretreatment with endotoxin reduced renal injury
      induced by methemoglobin, but not ischemia. CONCLUSIONS: The resistance to injury
      conferred by endotoxin in Gly-ARF involves induction of an antioxidant response,
      consisting of increased heme oxygenase and ferritin synthesis. This coupled
      response allows degradation of heme as well as chelation of iron, thus decreasing
      oxidant-mediated tissue injury. This novel mechanism of endotoxin-induced
      resistance may be applicable not only to Gly-ARF but also to other models of
      tissue injury in which enhanced oxidative stress is implicated.

PMID- 7723288
TI  - What is your diagnosis? Hypoadrenocorticism.

PMID- 7723289
TI  - Treatment of canine nictitans plasmacytic conjunctivitis with 0.2 per cent
      cyclosporin ointment.
AB  - Nictitans plasmacytic conjunctivitis, commonly referred to as plasma cell
      infiltrate of the nictitans or plasmoma, was diagnosed in 12 dogs (23 eyes) on
      the basis of clinical signs and nictitans conjunctival biopsy specimens. These
      dogs underwent a clinical therapeutic trial with twice daily 0.2 per cent
      cyclosporin ophthalmic ointment. Response to therapy was monitored over a six
      week period and repeat biopsy specimens were then taken. Significant (P < 0.05)
      reductions between pre- and post trial scores were recorded for: mucopurulent
      ocular discharge quantity; degree of bulbar conjunctival hyperaemia; areas of
      nictitans hyperaemia, thickening and depigmentation. Schirmer tear test values
      significantly increased between the start and end of treatment. Biopsy specimens
      were subjected to selective detection procedures for plasma cells (methyl green
      pyronin staining) and T lymphocytes (CD3 antigen labelling). Mean cell counts
      showed a significant reduction in plasma cell numbers, but the trend towards
      reduced T lymphocyte numbers was not significant.

PMID- 7723290
TI  - Encephalomyelopathy in young cats.
AB  - Nineteen cats, aged three to 16 months, developed neurological signs including
      hindleg paralysis, head shaking, nystagmus, defective vision and reduced
      proprioception. Most of the animals were in cat colonies in research centres and
      were derived from specific pathogen-free stock. One was referred from veterinary
      practice. Over 40 per cent of litters could be affected constituting a serious
      commercial loss. Wallerian degeneration affected long tracts in the spinal cord
      and variously in the brain stem and cerebral white matter. In seven animals there
      was loss of Purkinje cells in the cerebellum and in eight there was neuronal loss
      in the spinal cord. Gliosis accompanied all changes. Although no viral agent was
      isolated the clinical pattern of the disease and evidence from other cases
      reported in the literature suggest an infectious cause.

PMID- 7723291
TI  - Effect of the interval between feeding and drug administration on oral ampicillin
      absorption in dogs.
AB  - Eight dogs of various breeds received single oral doses of 20 mg/kg bodyweight
      ampicillin at four different time intervals relative to feeding a meal. In
      treatment A the dogs were fasted for 12 hours before and after ampicillin
      administration. In treatment B the dogs received ampicillin immediately after, in
      treatment C one hour before and in treatment D two hours after the meal. Each dog
      received these treatments during a period of feeding dry and canned dog food
      according to an 8 x 8 Latin square design. Blood samples were taken at specified
      time intervals after drug administration by jugular venepuncture. Antibiotic
      concentrations in plasma were determined by microbiological assay. Non
      compartmental pharmacokinetic parameters were calculated from the individual
      concentration-time curves and were compared by non-parametric statistic tests
      between treatments and types of food. With both dry and canned food ampicillin
      absorption was impaired when the drug and food were given at the same time
      (treatment B) as compared to the absorption in fasting dogs (treatment A and C).
      On dry food, drug absorption was also decreased in treatment D. It is recommended
      for clinical purposes to give ampicillin to fasted dogs, and to wait at least one
      hour before feeding. After a meal (dry food) waiting two hours until drug
      administration is not sufficient to avoid impaired ampicillin absorption.

PMID- 7723292
TI  - Medial displacement of the tendon of origin of the biceps brachii muscle in 10
      greyhounds.
AB  - The history, clinical signs and treatment of 10 greyhounds with medial
      displacement of the tendon of origin of the biceps brachii muscle secondary to
      rupture of the transverse humeral ligament are described. The aetiology of the
      condition and the prognosis for return to racing are discussed.

PMID- 7723293
TI  - Focal cystic endometrial hyperplasia in a bitch.
AB  - Rapid abdominal enlargement and weight gain occurred in a four-year-old Rhodesian
      ridgeback bitch in late oestrus. The bitch was nulliparous. Severe cardiovascular
      dysfunction followed and an exploratory laparotomy was performed. A large,
      single, spheroid mass weighting 17 kg was located in the middle section of the
      left uterine horn. A diagnosis of sterile, focal, cystic endometrial hyperplasia
      was made from gross pathology, histopathology and bacteriology. The bitch made a
      complete recovery following an ovariohysterectomy.

PMID- 7723294
TI  - Ultrasonographic findings in a basenji with immuno-proliferative enteropathy.
AB  - The ultrasonographic findings in a one-and-a-half-year-old female basenji with
      immunoproliferative enteropathy are described. On ultrasonographic examination,
      generalised thickening of the small bowel wall was found, ranging between 4 and 6
      mm. The normal layered appearance of the intestinal wall was replaced by three
      distinct layers; an innermost enlarged hyperechogenic layer; an enlarged poor
      echogenic layer, and an outer hyperechogenic layer. These findings are consistent
      with the histopathological appearance of this particular chronic inflammatory
      bowel disease, since the inner layer probably represents the infiltrated mucosa,
      the middle layer the infiltrated lamina propria and the outer layer the serosa.
      Thus, the ultrasonographic finding of generalised thickening of the intestinal
      wall in a basenji presenting with chronic diarrhoea, weight loss, anorexia or
      vomiting is strongly indicative of immunoproliferative enteropathy.

PMID- 7723295
TI  - Trypanosoma congolense infection in two dogs.
AB  - Trypanosomiasis, caused by Trypanosoma congolense, was diagnosed for the first
      time in Israel in two boxer dogs imported from Kenya. The dogs developed clinical
      signs two days after arrival and succumbed to the disease within four days. The
      major clinical and clinicopathological findings included anaemia, haemorrhages,
      lymphadenomegaly, hepatosplenomegaly and neurological signs. Histopathology
      showed lymphocytic-plasmacytic infiltration in the skin, brain, meninges, kidney
      and liver.

PMID- 7723296
TI  - Cocapropylene (propylcocaine) formation by human liver in vitro.
AB  - Formation of cocapropylene (CP), the n-propyl analogue of cocaine, by human liver
      has been demonstrated for the first time through incubation of whole liver
      homogenates with cocaine (COC) and n-propanol (PrOH). The formation of CP was
      noted by 30 min in each case, and it continued throughout the 6-h study period.
      The concentration of COC declined throughout each incubation. Sodium fluoride was
      found to inhibit completely the formation of CP. For control purposes, the
      capability of each liver to generate cocaethylene (CE), the known
      transesterification product of COC and ethanol (EtOH), was established by
      separate incubation of the homogenate with COC and EtOH. Concentrations of COC,
      CP, and CE in the respective homogenates were measured by reversed-phase high
      performance liquid chromatography, whereas those of EtOH and PrOH were measured
      by gas-liquid chromatography.

PMID- 7723297
TI  - Interference by nonsteroidal anti-inflammatory drugs in EMIT and TDx assays for
      drugs of abuse.
AB  - Fourteen nonsteroidal anti-inflammatory drugs were evaluated for interference in
      EMIT and TDx assays for drugs of abuse. Only tolmetin demonstrated significant
      interferences in the EMIT assay. Urine samples that contained high concentrations
      of tolmetin (1800 mg/L) had characteristic high molar absorptivity at the
      wavelength used in EMIT assays (340 nm). Consequently, EMIT analysis of samples
      resulted in instrument error alarms on a Hitachi 704 instrument and depressed
      milliabsorbance values (delta A) relative to calibrators. Similar results were
      obtained with urine samples collected from an arthritic patient after the
      administration of 200 and 400 mg of tolmetin. When tolmetin samples were mixed
      with drugs of abuse, depressed delta A values were noted in all assays. Samples
      containing opiates and cannabinoids tested negative, and instrument error alarms
      were produced with samples that contained amphetamines. A gas chromatographic
      mass spectrometric (GC-MS) assay for benzoylecgonine in the presence of tolmetin
      was successful, and no interferences were noted. Similar interferences by
      tolmetin were not observed in TDx assays, probably because of the different
      wavelength (525 nm) used in this assay. However, a potential for false-positive
      results in the TDx benzodiazepine assay was noted for urine samples containing
      high concentrations of fenoprofen, flurbiprofen, indomethacin, ketoprofen, and
      tolmetin. Generally, it was concluded that the presence of tolmetin in urine
      samples could lead to the production of unacceptable results by the EMIT assay
      for drugs of abuse. However, TDx and GC-MS assays were useful alternatives for
      the analysis of urine samples suspected of containing tolmetin.

PMID- 7723298
TI  - Quantitative analysis of fentanyl in pharmaceutical preparations by gas
      chromatography-mass spectrometry.
AB  - Fentanyl (1-[2-phenethyl]-4-N-[N-propionylanilino]piperidine) is a potent
      synthetic opiate commonly used for surgical analgesia and sedation. Reports of
      abuse of this highly addictive drug among health care personnel have prompted the
      need to verify the concentration in the unused portion of single-dose ampules
      returned to the pharmacy. We describe a simple quantitative method for the
      analysis of fentanyl citrate (Sublimaze) in syringes returned to the pharmacy
      following surgery. Fentanyl citrate (0.1 mL) and 2H5-fentanyl (internal standard,
      0.05 mL, 100 mg/L) were extracted with Toxi-A tubes (Toxi-Lab, Irvine, CA) and
      analyzed by gas chromatography-mass spectrometry. Calibration was linear from 1
      to 60 mg/L (correlation coefficient of 0.997, n = 13) and had a limit of
      detection of 0.4 mg/L. Mean recovery at concentrations from 5 to 50 mg/L was 89%
      (range, 69-104%). No interferences were found with morphine, ketamine, midazolam,
      sufentanil, or alfentanil. These drugs were not selected for their potential
      chromatographic interference but for their availability in surgical syringes.
      This assay is useful in verifying that any unused fentanyl is discarded according
      to narcotic regulations, thereby avoiding the possibility of diversion for
      illicit consumption.

PMID- 7723299
TI  - Cyanide assay: statistical comparison of a new gas chromatographic calibration
      method versus the classical spectrophotometric method.
AB  - This work compares two different methods for assaying hydrogen cyanide, a
      spectrophotometric method and a headspace gas chromatographic method, each with
      its own reference standard generation. In the first method, the reference
      standards are cyanide solutions. In the second method, the reference standards
      are based upon the in situ reduction of ethyl thiocyanate by dithiothreitol to
      produce hydrogen cyanide. Furthermore, hydrogen cyanide concentration in the
      blood of patients who were poisoned by smoke inhalation or who committed suicide
      by cyanide ingestion is determined using both methods. Results are discussed
      using statistical comparison.

PMID- 7723300
TI  - Screening, identification, and quantitation of benzodiazepines in postmortem
      samples by HPLC with photodiode array detection.
AB  - A high-performance liquid chromatographic method has been developed for the
      simultaneous analysis of eight frequently used benzodiazepines and some of their
      metabolites in postmortem samples. The method includes a liquid-liquid extraction
      with n-hexane-ethyl acetate (70:30, v/v), gradient elution of a C8 reversed-phase
      column with an alkaline water-methanol eluent free of buffer salts, and
      photodiode array detection. This allows rapid detection, a purity check,
      identification, and quantitation of the eluting peaks. Recovery and linearity
      data are good for the chosen parent compounds. The validated procedure has been
      applied routinely in forensic toxicological analyses. The elimination of the
      buffer from the eluent results in a robust procedure, free of technical problems
      and long rinsing periods.

PMID- 7723301
TI  - Monitoring drug use with a sweat patch: an experiment with cocaine.
AB  - Eighteen male subjects participated in a clinical study to examine a skin patch
      method of monitoring drug use. On the first day of each of two periods, 14 Band
      aid type collection devices (sweat patches) were applied to a subject's torso,
      biceps, and back. On the following day, the subject took 50 or 126 mg cocaine
      hydrochloride intranasally. A 1-week interval separated treatment periods, and
      the order of dose levels was counterbalanced. On the days subjects received
      cocaine, one patch was removed before treatment, and five were removed after
      treatment. Subjects then returned over the next 7 days for removal of the
      remaining patches. They provided urine samples immediately after each patch
      removal. A group of 18 nondrug users also wore patches for up to 12 days.
      Analysis of the patch content yielded cocaine levels from the cocaine subjects
      that accurately reflected usage. Mean levels for 16 subjects were significantly
      different for the two treatment doses. However, given the between-dose and
      between-subject variability, the data cannot be used to determine either dose or
      time of use. The data do indicate, however, that the patch technology can be used
      to diagnose a single episode of cocaine use as far back as 7 days.

PMID- 7723302
TI  - Influence of biological matrix on chromatographic behavior and detection of
      selected acidic, neutral, and basic drugs examined by means of a standardized
      HPLC-DAD system.
AB  - Human serum, autopsy blood, and liver samples were extracted by means of liquid
      liquid extraction at acidic and at basic pH and at basic pH following acid
      hydrolysis. Six selected basic and six selected acidic or neutral drugs were
      added to the extracts. The spiked and blank samples were examined by means of
      reversed-phase high-performance liquid chromatography (HPLC) under standardized
      conditions using diode array detection. The retention index (RI) values of drugs
      were determined using a 1-nitroalkane scale and secondary standards. The RI
      values were virtually unaffected by biological matrix. On the other hand, the
      detection of some substances may be impaired by matrix peaks occurring regularly
      in biological extracts. The retention index values and UV spectra of three
      identified (phenethylamine, tryptamine, and indole) and nine unidentified
      substances were included in an HPLC database.

PMID- 7723303
TI  - Validity testing of the accuPINCH THC test.
AB  - Self-contained drug-testing kits are currently being marketed for a variety of
      drugs of abuse. These tests are designed to provide rapid access to test results
      without the need for laboratory facilities. This report describes a validity
      study of the accuPINCH THC test, a self-contained test for cannabinoids in urine.
      Three healthy male volunteers with a history of marijuana use participated in the
      clinical study. Each subject smoked one, two, or four marijuana cigarettes (2.6%
      THC) on each test day. Urine samples were collected and incorporated into a
      specimen set consisting of 178 clinical samples, 72 urine samples containing
      known amounts of drug, and 50 drug-free urine samples. The specimen set was
      randomized and analyzed under blind conditions by the accuPINCH test and by gas
      chromatography-mass spectrometry (GC-MS) for 11-nor-9-carboxy-delta 9
      tetrahydrocannabinol (THCCOOH). AccuPINCH results were interpreted independently
      by three readers as positive at either two calibration points (positive A < 100
      ng/mL THCCOOH; positive B > or = 100 ng/mL THCCOOH) or negative. Concordance
      analysis was performed by comparison of the accuPINCH results with GC-MS. In
      addition, the effects of changes in sample turbidity, temperature, and assay
      reading time on test outcome were assessed. For the clinical samples, positive B
      results were associated exclusively with THCCOOH concentrations greater than or
      equal to 15 ng/mL, whereas positive A and negative results were obtained at all
      concentrations. All drug-free urine samples were interpreted as either negative
      or positive A. The test demonstrated relatively low cross-reactivity with THC and
      other cannabinoids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723304
TI  - Rapid, sensitive, and noninvasive sampling technique for determination of
      chloroform in alveolar breath.
AB  - A sampling technique for the determination of chloroform in alveolar breath is
      presented. Subjects exhale in a homemade device for collection of the alveolar
      fraction. The collected sample is transferred to a partially evacuated headspace
      vial and subsequently analyzed by capillary gas chromatography using electron
      capture detection. Concentrations greater than 50 micrograms/m3 can readily be
      detected. Good correlation observed between chloroform levels in alveolar breath
      and plasma validates the sampling technique.

PMID- 7723305
TI  - Clarification of benzodiazepine structural classes.

PMID- 7723306
TI  - Differing attitudes toward people who have AIDS.

PMID- 7723307
TI  - The predictive relationship between academic self-concept, achievement
      expectancies, and grade performance in college calculus.

PMID- 7723308
TI  - Children's and adults' memories for self-schema consistent and inconsistent
      content.

PMID- 7723309
TI  - Factors affecting the learning environments and school-related outcomes of
      Australian adolescents.
AB  - In this follow-up study of an earlier investigation (Marjoribanks, 1991),
      discriminant analysis was used to examine relationships between social
      categories, defined by ethnicity, gender, and social status, and measures of
      adolescents' family and school-learning environments and their school-related
      outcomes. There were 470 16-year-old Australian adolescents and their parents
      from Anglo-Australian, Greek, and Southern Italian families in the sample. The
      results of this study and of the earlier investigation suggest that differences
      in the profiles of students' learning environments and school outcomes are
      related particularly strongly to ethnicity, but that within ethnic groups there
      are significant gender and social-status variations in such profiles.

PMID- 7723311
TI  - Bacterial translocation and intestinal capillary permeability following major
      liver resection in the rat.
AB  - Bacterial infections constitute a major cause of morbidity and mortality after
      major liver resection and mechanisms of this type of complication have been
      poorly understood. The present study evaluated the translocation of enteric
      bacteria to mesenteric lymph nodes, viscera, and the systemic circulation and gut
      capillary permeability of a fine ultrastructural tracer in rats subjected to sham
      hepatectomy or 70% hepatectomy. Furthermore, the preventive effects of water
      soluble ethylhydroxyethyl cellulose (EHEC) were studied. Cultures of all samples
      from rats subjected to sham hepatectomy or 70% hepatectomy with preoperative
      intravenous administration of EHEC were bacteriologically negative. The incidence
      of bacterial translocation from the gut to the systemic circulation and
      mesenteric lymph nodes was 30 and 80%, respectively (P < 0.01), and to the liver
      and kidneys 50 and 40%, respectively (P < 0.05), 12 hr after 70% hepatectomy.
      Intestinal capillary permeability and endothelial cell membrane permeability
      increased with the development of bacterial translocation. Translocating bacteria
      appeared within the cytoplasm of capillary endothelial cells. EHEC restored the
      changes in gut capillary permeability induced by major liver resection. These
      results indicate that gut capillary permeability may play an important role in
      maintaining the integrity of the gut barrier function and that increased
      permeability may be associated with the development of gut barrier failure.

PMID- 7723310
TI  - Individualism and collectivism as considerations in cross-cultural health
      research.

PMID- 7723312
TI  - Quantitating intestinal ischemia with nitroblue tetrazolium salts.
AB  - We evaluated a spectrophotometric nitroblue tetrazolium (NBT) reduction assay as
      a technique to quantitate experimental intestinal ischemic injury. NBT is a
      tetrazolium salt that is reduced by mitochondrial coenzymes to form a blue
      formazan dye which can be measured on a spectrophotometer. We used a rat model of
      progressive intestinal ischemia to compare NBT reduction with standard histologic
      grading by light microscopy. Isolated segments of small intestine were made
      ischemic for periods of 15, 30, 60, 90, and 120 min in each of five rats (no
      reperfusion). A portion of each segment was prepared for both NBT reduction assay
      and blinded histologic grading. The reproducibility of these results was then
      tested in a second identical study of four rats (Part 2). When compared to
      nonischemic segments of intestine, NBT reduction was significantly decreased
      after 30 min of ischemia (P < 0.05, ANOVA) and continued to decrease as ischemic
      time increased. These findings were reproduced in the second experimental group.
      Overall, NBT reduction correlated closely with duration of ischemia (r = 0.81, P
      < 0.001) and histologic grade (r = 0.77, P < 0.001). Based on criteria developed
      in Part 1, NBT reduction had a sensitivity of 100% and a specificity of 94% for
      detecting ischemia > or = 30 min in Part 2. We conclude that the
      spectrophotometric NBT assay in an accurate technique for quantitating small
      intestinal ischemic injury which also gives useful information about the
      functional status of mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723313
TI  - Effects of TPN on brain, liver, and food intake in rats.
AB  - Postulating that total parenteral nutrition (TPN) has a direct metabolic effect
      in the brain which may be similar to that in the liver, we studied the effects of
      TPN on brain glycogen and triglyceride in rats. Control rats (n = 24) received
      normal saline via jugular catheter for 18 days; TPN rats (n = 24) had normal
      saline for 10 days and then TPN-100 for 4 days, followed by normal saline for 4
      more days. TPN-100 (caloric ratio glucose: fat:amino acid = 50:30:20) provided
      100% of the rat's daily caloric needs. Chow and water were available ad libitum
      during the study. Eight rats from each group were sacrificed after 1 and 4 days
      of TPN-100, and 4 days after stopping TPN-100. Glycogen in brain and liver
      glycogen, triglyceride, and glycogen synthetase and phosphorylase were measured,
      as were plasma glucose and insulin. Data were evaluated using Student's t test.
      With TPN, the following occurred: (a) an 85% decrease (P < 0.05) of spontaneous
      food intake; (b) an elevated plasma glucose; (c) a three- to fivefold increase (P
      < 0.01) in plasma insulin; (d) a 23% increase (P < 0.05) in whole brain glycogen
      but a 22-33% decrease (P < 0.05) in liver glycogen; (e) liver glycogen synthetase
      and phosphorylase activity were unchanged while whole brain glycogen synthetase
      activity decreased by 27% (P < 0.05) and phosphorylase activity increased by 10
      16%; and (f) whole brain triglyceride content did not change, although there was
      a 155-241% increase (P < 0.01) in liver triglyceride.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7723314
TI  - Surgical approach for maintaining nonischemic conditions of the liver in acute
      hepatic vein obstruction.
AB  - To establish a possible surgical approach for preventing warm ischemic injury to
      the liver followed by hepatic vein occlusion (HVO), the hepatic hemodynamics and
      energy metabolism were investigated in an acute canine HVO model with and without
      hepatic arterial blood flow. Arterial blood ketone body ratio (AKBR;
      acetoacetate/3-hydroxybutyrate) and adenylate energy charge potential (ECP = [ATP
      + 1/2 ADP]/[ATP+ADP+AMP]) of the liver tissue were measured during and after 60
      min of HVO. In the group with hepatic arterial blood flow, in which arterial
      blood was drained by hepatofugal portal flow via the venovenous bypass, total
      hepatic blood flow, portal vein pressure, ECP, and AKBR were maintained at almost
      normal level after the termination of HVO, resulting in the survival of all
      animals for 3 days or longer. By contrast, in the group without hepatic arterial
      blood flow (warm ischemic group), total hepatic blood flow was maintained at less
      than 60% of preischemic value, and portal vein pressure gradually increased up to
      twice the preischemic value. ECP decreased from 0.81 +/- 0.06 to 0.71 +/- 0.07
      along with increasing portal venous pressure, and AKBR also decreased from 1.23
      +/- 0.12 to 0.63 +/- 0.23, resulting in no survival longer 6 hr. It was concluded
      that hepatic arterial blood flow during HVO, if drained as hepatofugal portal
      flow, could maintain nonischemic conditions in the liver, despite vena cava
      obstruction, by providing an alternate outflow via reversed flow in the portal
      vein.

PMID- 7723315
TI  - Ethanol ingestion potentiates PMN migration into small intestine after ischemia.
AB  - Neutrophils have been identified to play a major role in ischemia/reperfusion
      injury through several mechanisms. Neutrophil migration into reperfused gut may
      reduce bacterial translocation, but may also enhance the reperfusion injury.
      Ethanol ingestion impairs cutaneous chemotaxis, but its effects on neutrophil
      migration to postischemic small bowel are unknown. This study investigates the
      effects of ethanol on small bowel accumulation of neutrophils after
      ischemia/reperfusion. Ninety-five rats were divided into five groups; normal
      control, sham operation, ethanol-sham, ischemia, and ethanol-ischemia groups.
      Ethanol was given once acutely by gavage (3 g/kg, 20% solution) to the animals in
      the ethanol-sham and the ethanol-ischemia groups 4 hr before ischemic injury.
      Ischemia was produced for 1 hr by placing a vessel loop around the superior
      mesenteric vessels. After 1 hr, 87% of animals had gut ischemia and the loop was
      removed. Three hours later the small bowel was examined for necrosis and the
      reperfused viable small bowel was extirpated for measurement of neutrophil
      infiltration by colorimetric assay for myeloperoxidase (MPO), an enzyme
      restricted to neutrophils. Both ethanol and ischemia/reperfusion produced
      significant independent increase in the MPO activity. When ethanol was given
      prior to ischemia, the MPO activity was further increased by statistically
      significant margin. The present study demonstrated that ethanol enhanced the
      effects of gut ischemia/reperfusion injury on PMN accumulation into the
      intestinal wall. These observations suggest that ethanol may potentiate ischemic
      injury to the gut and lead to increased problems when gut blood flow is
      significantly impaired.

PMID- 7723316
TI  - Biliary nonmucin glycoproteins in patients with and without gallstones.
AB  - Total protein, mucin, and specific nonmucin glycoproteins are proposed
      pronucleating agents in cholesterol gallstone pathogenesis. However,
      characterization of specific nonmucin glycoproteins in patients with and without
      gallstones is unknown. Furthermore, nonmucin glycoproteins may be qualitatively
      different in patients with and without gallstones. Total protein and total and
      specific nonmucin glycoproteins were studied in gallbladder bile of 43 patients
      with cholesterol gallstones and 13 patients without gallstones. Patients with
      cholesterol gallstones had higher concentrations of both total protein and
      nonmucin glycoproteins than that observed in control patients (P < 0.05). SDS gel
      electrophoresis of nonmucin glycoproteins demonstrated an 84-kDa protein that was
      present significantly more often in patients with cholesterol gallstones (87% vs
      8%, P < 0.05). Proposed 130- and 42-kDa pronucleating and 120-kDa anti-nucleating
      nonmucin glycoproteins were present in similar percentages in gallstone and
      control bile. Moreover, gallbladder bile of patients with the 84-kDa protein
      nucleated 50% faster than model bile and > 100% faster than that of patients
      without this protein (P < 0.05). The currently described gallbladder
      pronucleating and anti-nucleating proteins are found with equal frequency in
      cholesterol gallstone and control patients. However, an 84-kDa protein is found
      more commonly in gallstone patients and was associated with a shortened crystal
      observation time. Thus, this glycoprotein may be important in cholesterol
      gallstone pathogenesis.

PMID- 7723318
TI  - Oxidant stress: the role of the glutathione redox cycle in skin preconditioning.
AB  - The role of the glutathione redox cycle in cellular protection form skin necrosis
      during the ischemic stress response (preconditioning) is unknown. In this series
      of experiments, we tested the hypothesis that oxidant stress reduces available
      total glutathione during injury and contributes to skin necrosis in flaps. Dorsal
      skin flaps (10 x 4 cm) were raised as acute flaps and skin grafts were obtained
      from the flaps at 0, 1, 4, 6, 12, or 24 hr. Some flaps were preconditioned as
      bipedicle flaps for 24, 48, 72, or 96 hr and the distal attachment divided before
      skin grafts were obtained 24 hr later. Flap survival was measured at 7 days.
      Total glutathione (GSH) and oxidized GSH (GSSG) were extracted and their levels
      determined enzymatically. Tissue GSH reductase (GR) activity was assayed with a
      spectrofluorometer and expressed as mumoles of NADPH oxidized/hr/g. Biochemical
      data were compared between the proximal and distal ends of the flaps using a two
      tailed Student t test while differences between groups were compared using ANOVA.
      Skin necrosis was 5.4 +/- 0.12 cm in the distal ends at 7 days in acute flaps,
      while there was no skin necrosis in flaps preconditioned for 7 days. In acute
      flaps, total GSH levels fell precipitously in the distal end at 24 hr (P < 0.05).
      However, after 72 hr of preconditioning, the GSH levels in the distal end of the
      flap remained elevated while GSSG levels were undetectable. At 24 hr of ischemia,
      GR activity was 79 +/- 4 in the distal ends of acute flaps, while after
      preconditioning and 24 hr of ischemia, the GR activity increased to 172 +/- 13 in
      the distal ends (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723317
TI  - Parenteral antibiotics and selective intestinal decontamination do not prevent
      enteric bacterial overgrowth or translocation observed in a swine model of small
      bowel transplantation.
AB  - Alterations in the luminal microflora and increased intestinal translocation have
      been reported to occur following experimental and clinical small bowel
      transplantation (SBT). Selective intestinal decontamination (SID) has been used
      to prevent luminal overgrowth and bacterial translocation. Despite the wide use
      of SID in clinical SBT, there are no data supporting its usefulness in this
      situation. Thus, the aim of this investigation was to examine the effects of
      cyclosporine A (CsA) and SID upon bacterial overgrowth and translocation in a
      swine model of SBT. Nineteen Large White female pigs weighing 30 +/- 2 kg
      underwent a total orthotopic SBT and were randomly allocated to one of the
      following experimental groups as follows: Group 1 (No. 8) CSA 25 mg/kg body
      weight (b.w.)/day administered subcutaneously and Cefazolin 2 g/day im. Group 2
      (No. 6) received the identical immunosuppression but the Cefazolin 2 g/day im was
      discontinued on the 5th Postoperative Day (pod) and switched to a SID regimen
      consisting of Vancomycin, 1 g, Nystatin, 500,000 IU, Colistin, 1,500,000 IU, and
      Tobramycin, 100 mg, given through a gastrostomy tube. Group 3 (No. 5) received no
      immunosuppression but antibiotic consisting of Cefazolin 2 g im/day. Group 4 (No.
      7) underwent a small bowel autotransplantation. Group 4 received SID as in group
      2 but no immunosuppression was given. Finally, 17 normal animals were sham
      operated and were used as normal controls (N group). The animals in groups 1, 2,
      and 4 were sacrificed on the 29th pod. Those in group 3 were sacrificed on the
      7th pod.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723319
TI  - Auxiliary heterotopic liver graft using splenopancreatic venous blood flow in
      pig.
AB  - An original model of auxiliary heterotopic liver graft perfused by
      splenopancreatic venous blood flow is studied in pig. Separate portal inflow is
      performed for each liver and permits efficient function in both graft and native
      liver. Ten pigs were evaluated 90 days after transplantation, five without portal
      graft reperfusion (group 1) and five with portal graft reperfusion by
      splenopancreatic venous blood flow (group 2). Mean biliary output was 4.8 +/- 3.3
      ml/hr in group 1, 9.6 +/- 2.3 ml/hr in group 2; biliary conjugated bilirubin
      level was 0 in group 1, 145 +/- 117 mumol/liter in group 2; intrahepatic glycogen
      level was 0.9 +/- 1.1 g% in group 1, 4.25 +/- 1.56 g% in group 2. Livers and
      grafts were weighed to evaluate hepatic mass on the 90th day. A histological
      examination was performed for each graft and native liver. It was shown that an
      auxiliary liver graft perfused by splenopancreatic venous blood flow presents
      satisfying metabolic function for 3 months, without atrophying and without
      functional impairment of native liver. This original model could be indicated in
      acute hepatic failure if regeneration of native liver is expected or in metabolic
      disease when total hepatectomy of the native liver may be unnecessary.

PMID- 7723320
TI  - Impaired connective tissue repair in streptozotocin-induced diabetes shows
      ultrastructural signs of impaired contraction.
AB  - Streptozotocin-induced diabetes mellitus is known to impair connective tissue
      repair in the perforated rat mesentery. The aim of the present investigation was
      to study quantitatively by morphometrical techniques the influence of diabetes on
      some aspects of the cellular ultrastructure related to connective tissue
      contraction in such healing. The cellular volume density increased significantly
      with time, presumably as a consequence of disappearance of interstitial edema. No
      difference was found in the amount of healing tissue formed between controls and
      diabetics. The surface volume density of the plasma membrane was significantly
      higher in control animals on Days 1-10, indicating an increased number of
      cellular protrusions and spikes which relate to the motility of the cells. The
      volume density of contractile filaments did not differ between controls and
      diabetics. The results suggest a reduced surface density of plasma membrane in
      diabetic cells, a finding which is compatible with reduced wound contraction in
      diabetes.

PMID- 7723321
TI  - Healing comparison of small intestine submucosa and ePTFE grafts in the canine
      carotid artery.
AB  - Continuing investigation of small-diameter vascular graft materials suggests that
      unacceptable graft complications continue and that the ideal material has not yet
      been found. We compared healing of xenogeneic small diameter grafts (3.5 to 5.0
      mm diameter) made from porcine small intestine submucosa (SIS) implanted in the
      carotid artery to expanded polytetrafluorethylene (ePTFE) in the contralateral
      carotid in 8 dogs. Two dogs were sacrificed for graft evaluation at 7, 28, 90,
      and 180 days after surgery. Only one SIS graft was occluded at 28 days and the
      other 7 were patent. Six of 8 ePTFE grafts were occluded with thrombi. One was
      patent at 7 and one at 90 days. At 7 days post-implant, the luminal surface of
      the SIS graft was covered by a thick (30 microns), compact fibrin meshwork. By 28
      days endothelial cells were seen completely covering the fibrin meshwork which
      stained for FVIII-related antigen. Smooth muscle cells were observed in the neo
      intima. Most ePTFE grafts had fibrin on the luminal surface which formed fibrin
      thrombi with platelets and numerous red blood cells. Complete endothelial
      coverage of the ePTFE grafts was not observed by 180 days. There was not a
      pronounced neointima seen on the luminal surface of the graft. The vasa vasorum
      was present in the fibrous capsule surrounding the ePTFE graft, but it did not
      penetrate into the graft as seen in the SIS graft. At 90 days the SIS vascular
      graft had the histological appearance similar to a normal artery. The SIS graft
      potency and healing characteristics were superior to the synthetic ePTFE graft
      and warrant further investigation.

PMID- 7723322
TI  - Calcitonin gene-related peptide (CGRP) upregulates the restitution of rat gastric
      mucosa in vitro.
AB  - Calcitonin gene-related peptide (CGRP) is a neuropeptide with many significant
      effects on gastrointestinal function. Among these are gastroprotective effects
      such as inhibition of acid secretion and increase in gastric mucosal blood flow.
      To evaluate whether CGRP has a direct protective effect on gastric mucosa, we
      examined the influence of the peptide on restoration of mucosal integrity
      following mild damage. Mucosal integrity was assayed by measurement of the
      transmucosal potential difference of tissue mounted in an Ussing chamber
      perfusion system. Undamaged mucosa maintained a potential difference of
      approximately -64 mV in both control tissues and tissues serosally treated with
      CGRP. Damage was induced by exposure of the gastric mucosa to solutions of 0.5,
      1.0, and 2.0 M sodium chloride. Each of the hyperosmolar solutions caused mucosal
      injury as evidenced by a rapid decrease in PD, with the most concentrated
      solution causing the greatest decrease and the slowest and least complete
      recovery. CGRP treatment led to a significantly more complete recovery of PD when
      injury was caused by 0.5 M but not by either 1.0 or 2.0 M NaCl. We conclude that
      CGRP is capable of directly enhancing recovery of mucosal integrity after mild
      but not severe damage of rat gastric mucosa in vitro.

PMID- 7723323
TI  - Neural mechanisms in basal and meal-stimulated ileal absorption.
AB  - The ingestion of a meal stimulates absorption from the jejunal lumen and is
      dependent on intact neural pathways. Few studies of ileal absorptive responses to
      a meal have been performed. This study tested two hypotheses: (1) a meal
      stimulates ileal glucose, water, and ion absorption, and (2) intact intestinal
      neurotransmission is necessary to maintain the basal and meal-stimulated
      absorptive states in the ileum. Absorption studies (n = 50) using 14C-labeled PEG
      were performed on six dogs with 25-cm ileal Thiry-Vella fistulas (TVF). Four
      groups were randomly studied over 4 hr. Intraluminal oxethazaine (2 mg/dl) was
      administered to the TVF in Groups 2 and 4 after the 1st hour to produce neural
      blockade. A control volume of water was administered to the TVF in Groups 1 and 3
      after the 1st hour. A 480 kcal meal was ingested at the end of the 2nd hour in
      groups 3 and 4. Ileal water, ion, and glucose absorption were increased
      significantly (P < 0.05) by the ingestion of a meal. TVF oxethazaine
      significantly reduced (P < 0.05) basal water and ion absorption but had no effect
      on meal-stimulated absorption. Ileal absorption of water, ions, and glucose is
      significantly increased by the ingestion of a meal. Basal ileal absorption
      appears to be partly dependent upon intact neurotransmission. Postprandial ileal
      absorption appears to be independent of neural blockade, implicating circulating
      hormones, paracrine mediators, or neurotransmission within the myenteric plexus
      of the enteric nervous system as the primary modulators of meal-stimulated ileal
      absorption.

PMID- 7723324
TI  - Direction or reversal of preshunt portal blood flow as determinants of outcome up
      to 1 year after small-diameter prosthetic H-graft portacaval shunt.
AB  - Partial portal decompression (PPD) is gaining popularity in the treatment of
      portal hypertension. We have achieved PPD in over 80 patients by utilizing an 8
      mm prosthetic H-graft portacaval shunt (HGPCS). We have been pleased with the
      infrequency of encephalopathy and liver failure after shunting. While maintenance
      of portal blood flow would presumably play a role in outcome after shunting,
      changes in portal hemodynamic occurring within the first year after shunting are
      generally unknown. In 31 patients (Child's class 6% A, 61% B, 32% C) of an
      average age of 55 +/- 13.3 (SD) years undergoing HGPCS, clinical outcome was
      prospectively evaluated relative to the direction of portal blood flow determined
      before and after shunting and at 1 year after shunting using color-flow Doppler
      ultrasound. Preshunt hepatopetal flow reversed in 2/29 (7%) patients with
      shunting and in an additional 5/27 (18%) patients by 1 year after shunting. Death
      (due to alcoholism in 1, old age in 1) and encephalopathy (Child's class A = 1, B
      = 2, C = 1) were uncommon by 1 year after shunting. Eighty-one percent had
      excellent outcome (alive without encephalopathy or rebleeding) at 1 year. Though
      preshunt hepatopetal flow is generally maintained postshunt and after one year,
      maintenance of hepatopetal flow does not ensure an excellent outcome and reversal
      of hepatopetal flow does not pre-dispose to a suboptimal outcome. Outcome up to 1
      year after HGPCS is not determined by direction or reversal of portal blood flow.

PMID- 7723326
TI  - Lyme borreliosis.

PMID- 7723325
TI  - Impaired phorbol ester-induced hepatocyte proliferation in cirrhosis.
AB  - Cirrhotic livers are considered to regenerate less actively than normal livers
      after hepatic resection. Little is known about the mechanisms responsible for
      impaired capacity of regeneration in cirrhotic liver. In the present study, we
      investigated the effect of phorbol ester on hepatocyte proliferation in healthy
      and cirrhotic hepatocytes, using one of the phorbol esters, 12-O-tetradecanoyl
      phorbol-13-acetate (TPA), which has a direct effect on activation of protein
      kinase C (PKC). Cirrhosis was established by the administration of carbon
      tetrachloride and phenobarbital to rats. Healthy and cirrhotic hepatocytes were
      isolated from Wistar male rats by a two-step collagenase perfusion technique. DNA
      synthesis was estimated by [3H]thymidine incorporation into DNA and by
      autoradiographic nuclear labeling index. [3H]Thymidine incorporation was measured
      24 hr after hepatocytes were stimulated by appropriate reagents. TPA (50 nM)
      stimulated [3H]thymidine incorporation in healthy hepatocytes (control vs TPA,
      991 +/- 247 vs 2569 +/- 766 mean +/- SEM cpm/microgram DNA; P < 0.05), whereas
      TPA (50 nM) failed to stimulate in cirrhotic hepatocytes (control vs TPA, 1144 +/
      184 vs 1304 +/- 187 cpm/microgram DNA; NS). Staurosporine, a specific PKC
      inhibitor, suppressed [3H]thymidine incorporation in TPA-stimulated healthy
      hepatocytes (806 +/- 263 cpm/microgram DNA; P < 0.05); however, it had no effect
      on cirrhotic hepatocytes (1295 +/- 180 cpm/microgram DNA; NS). An
      autoradiographic nuclear labeling index exhibited the same results with
      [3H]thymidine incorporation. We conclude that TPA stimulates hepatocyte
      proliferation in healthy rat hepatocytes but has no effect on cirrhotic
      hepatocytes.

PMID- 7723327
TI  - Airway compromise in a patient with Parkinson's disease.

PMID- 7723328
TI  - Differentiation of tubo-ovarian abscess from pelvic inflammatory disease, and
      recent trends in the management of tubo-ovarian abscess.

PMID- 7723329
TI  - Blunt carotid artery injury.

PMID- 7723330
TI  - Polymicrobial myositis.

PMID- 7723331
TI  - Chronic histoplasmosis.

PMID- 7723332
TI  - Smoking cessation and the doctor's office.

PMID- 7723333
TI  - Healthy start.

PMID- 7723334
TI  - A good history usually gives a diagnosis.

PMID- 7723335
TI  - Preventive medicine series.

PMID- 7723336
TI  - War is hell.

PMID- 7723337
TI  - . . . where no one has gone before.

PMID- 7723338
TI  - Effects of spirapril and captopril on regional blood flow in chronic congestive
      heart failure: a comparison between a short- and a long-acting angiotensin
      converting enzyme inhibitor.
AB  - Spirapril is a new angiotensin-converting enzyme (ACE) inhibitor with a long
      duration of action. To determine whether duration of inhibition of serum ACE
      activity may affect regional blood flow (RBF), we compared spirapril with
      captopril, an ACE inhibitor with a short duration of action. Both the short- and
      long-term effects were studied in patients with mild to moderate congestive heart
      failure (CHF). Calf, renal, and hepatic BF measurements were performed in the
      morning before intake of the study medication; 24 h after the previous dose of
      spirapril (n = 9 patients) and 12 h after the previous dose of captopril (n = 9
      patients). Serum ACE activity after 1, 6, and 12 weeks was significantly reduced
      in patients receiving spirapril, but not in those receiving captopril. The
      decrease in mean arterial pressure (MAP) was more pronounced in the spirapril
      group. Calf BF showed a slight but not significant increase in both spirapril-
      and captopril-treated patients. Effective renal BF increased significantly only
      in patients treated with spirapril. Although filtration fraction (FF) tended to
      decrease in the spirapril group, the decrease was significant only in the
      captopril group. No changes were observed in hepatic BF. Cerebral BF (CBF)
      measurements were performed after intake of the first dose of study medication
      and after 12 weeks, immediately after drug intake. Significant reduction in MAP
      in the two treatment groups both after the first dose and after 12 weeks did not
      affect CBF. Despite a significantly prolonged decrease in MAP and serum ACE
      activity in spirapril-treated patients, no marked differences in RBF were noted
      between the two ACE inhibitors.

PMID- 7723339
TI  - Contractile effects of prostanoids on fetal rabbit ductus arteriosus.
AB  - We wished to determine whether any evidence indicates that the ductus arteriosus
      has prostanoid receptors coupled to contractile pathways and whether the
      sensitivity of the ductus to the dilator effect of prostaglandin E2 (PGE2) was
      inhibited by other prostanoids. Rings of ductus arteriosus were isolated from
      fetal New Zealand White rabbits (28 days of gestation) and mounted in vitro. In
      the presence of 1 microM indomethacin, the vessel was relaxed with either 300 nM
      forskolin or 10 nM PGE2, and cumulative concentration-contraction response curves
      to several synthetic prostanoids were obtained with or without a receptor
      antagonist when available. The vessel was also precontracted with 1 microM
      indomethacin and 25 mM K+ in 13-14.5 kPa O2, and cumulative concentration
      relaxation response curves to PGE2 were obtained with and without addition of
      prostanoids. In 300 nM forskolin, both U46619 and sulprostone caused
      concentration-dependent contractions of the ductus in the nanomolar range (EC50
      values, i.e., the interpolated molar concentration of the drug causing 50% of its
      own eventual maximum response of 33 and 42 nM, respectively). Responses to
      GR63799X and PGF2 alpha were complicated by the fact that these agonists caused
      relaxation at high concentrations (> or = 30 nM). The response to U46619 was
      shifted to the right by the thromboxane receptor antagonist EP 092. In 10 nM
      PGE2, U46619, sulprostone, and GR63799X elicited similar contractile responses,
      whereas PGF2 alpha had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723340
TI  - Improvement of cardiac function by allopurinol in patients undergoing cardiac
      surgery.
AB  - Allopurinol reduces formation of cytotoxic free radicals during myocardial
      ischemia/reperfusion in animals. To evaluate the effect of allopurinol on cardiac
      performance and metabolism after coronary bypass in humans, we divided 33
      patients into two groups: 15 patients (controls) received no allopurinol and 18
      patients received 200 mg allopurinol intravenously (i.v.) 1 h preoperatively.
      Hemodynamic measurements were made with a triple-lumen thermodilution pulmonary
      artery catheter before cardiopulmonary bypass (CPB), 30 min after completion of
      CPB and 6 h later in the intensive care unit (ICU). A catheter placed into the
      coronary sinus was used for blood sampling for measurement of lactate and
      creatine phosphokinase MB. Peripheral blood was obtained for measurement of
      xanthine oxidase activity (XO), uric acid, and thiol groups. A myocardial biopsy
      was taken for measurement of thiol group content and XO before CPB and after
      heparin neutralization with protamin (a few minutes after CPB). Treated patients
      had better recovery of cardiac output (CO) and left ventricular stroke work
      (LVSW) 30 min and 6 h after completion of CPB than did controls. Allopurinol
      significantly reduced plasma XO. Plasma concentrations of uric acid increased
      significantly in both groups 30 min after completion of CPB, but the increase in
      controls was greater (p < 0.02) than with allopurinol. Thiol group levels
      increased (p < 0.05) only in controls. Our results demonstrate improvement of
      cardiac function in coronary artery bypass surgery with allopurinol that is
      related to its metabolic effects consistent with protection against XO catalyzed
      free radical-mediated injury.

PMID- 7723341
TI  - Attenuation by R 56865, a novel cytoprotective drug, of regional myocardial
      ischemia- and reperfusion-induced electrocardiographic disturbances in
      anesthetized rabbits.
AB  - We investigated the antiischemic and antiarrhythmic effects of R 56865 in
      pentobarbital-anesthetized, open-chest rabbits subjected to 10 min regional
      myocardial ischemia and 20 min reperfusion, using two experimental protocols. In
      the first, R 56865 (0.02-0.16 mg/kg) was administered as a bolus intravenous
      (i.v.) injection 5 min before ligation of a branch of the left circumflex
      coronary artery (LCX); in the second, the drug, at the highest dose studied (0.16
      mg/kg), was injected by the same route during ischemia, 5 min after coronary
      artery ligation. Ischemia-induced ST segment increase and reperfusion-induced
      ventricular arrhythmias were determined in lead II of the four-limb ECG. Mean
      carotid arterial pressure and heart rate (HR) were also measured. When given
      before ischemia, R 56865 dose-dependently prevented ischemia-induced ST segment
      increase and reperfusion arrhythmias. The antiischemic and antiarrhythmic dose
      response curves were superimposable, suggesting a common mechanism of action. R
      56865 (0.16 mg/kg) fully attenuated ischemia-induced ST segment shift and
      ventricular arrhythmias on reperfusion. These protective effects were not
      associated with systemic hypotension or bradycardia. When high-dose R 56865 (0.16
      mg/kg) was given during ischemia, ST segment shift and ventricular arrhythmias on
      reperfusion were not attenuated. The results strongly suggest that R 56865
      affords protection against the deleterious effects of moderate ischemia by
      mechanisms not associated with an indirect reduction of cardiac work. R 56865 may
      elicit cardioprotection directly in ischemic tissue.

PMID- 7723342
TI  - Beta-adrenoceptor subtypes in human coronary artery: desensitization of beta 2
      adrenergic vasorelaxation by chronic beta 1-adrenergic stimulation in vitro.
AB  - We previously demonstrated that right atrial strips from patients treated with
      beta 1-selective antagonists exhibit sensitization of beta 2-adrenergic responses
      in vitro. We also showed that cardiac beta 2-adrenergic sensitization can be
      induced in normal subjects prospectively by beta 1-blocker treatment. To
      determine whether such cross-talk could be induced in vitro, we studied beta
      adrenoceptor-mediated vasorelaxation in deendothelialized rings of human coronary
      artery from patients undergoing cardiac transplantation. After incubation with 10
      microM phenoxybenzamine for 1 h, concentration-effect curves were determined to
      norepinephrine (NE) and epinephrine (EPI), with or without 300 nM CGP 20712A (a
      beta 1-selective antagonist), 50 nM ICI 118551 (a beta 2-selective antagonist),
      or both antagonists. Both beta 1- and beta 2-adrenergic components to
      vasorelaxation were detected. Other rings were incubated for 16 h with either 1
      microM NE (a selective beta 1-adrenoceptor agonist) or 300 nM CGP 20712A, or
      both. After washout, concentration-effect curves were determined to EPI in the
      presence of 300 nM CGP 20712A (beta 2-adrenergic responses). No differences in
      beta 2-adrenergic vasorelaxation were noted after prolonged incubation with
      either CGP 20712A or the combination of CGP 20712A and NE.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7723343
TI  - Species-dependent pharmacodynamic effects of the selective low Km cyclic AMP
      phosphodiesterase III inhibitors WIN 58993 and WIN 62005.
AB  - We describe the biochemical and pharmacologic effects of two novel fused
      pyridinones derived from milrinone: WIN 58993 and WIN 62005. Both WIN 58993 and
      WIN 62005 competitively inhibit cyclic GMP-inhibitable low Km cyclic AMP
      phosphodiesterase (PDE III) from rat heart and canine aorta with Ki values of 25
      +/- 3 and 26 +/- 5 nM, respectively, and are selective (at least 160-fold) for
      PDE III inhibition relative to other PDE isozymes. WIN 58993 and WIN 62005 were
      given to conscious, chronically instrumented rats and dogs intravenously (i.v.)
      or perorally (p.o.). Because the doses of WIN 58993 and WIN 62005 required to
      decrease mean arterial blood pressure (MAP) by 20% were estimated to be 0.9 and
      0.7 mg/kg, respectively, the compounds appear to be equipotent after acute i.v.
      administration in rats. However, the duration of the depressor responses in rats
      apparently differs since MAP remained significantly decreased 6 h after i.v. or
      p.o. administration of WIN 58993, but returned to control levels < or = 4 h after
      administration of WIN 62005. WIN 58993 may be slightly less potent than WIN 62005
      after acute i.v. administration to dogs since significant increases in left
      ventricular (LV)dP/dtmax first occurred at doses of 0.1 and 0.03 mg/kg,
      respectively. LVdP/dtmax significantly increased in 30 min and returned to
      baseline 3 h after p.o. administration of 1 mg/kg WIN 58993. After p.o.
      administration of 1 mg/kg WIN 62005. LVdP/dtmax was significantly increased in 30
      min and remained increased for at least 6 h. These data suggest that WIN 58993
      and WIN 62005 are potent, selective, p.o.-active inhibitors of PDE III.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7723344
TI  - Metabolic effects of atenolol and doxazosin in healthy volunteers during
      prolonged physical exercise.
AB  - Nonselective beta-blockers may reduce exercise performance, not only through
      hemodynamic but also through metabolic effects. During prolonged physical
      exertion, lipolysis induced by plasma epinephrine occurs through beta
      adrenoceptors of adipocytes. Therefore, beta-blockade may reduce release of free
      fatty acids (FFA) from adipocytes and consequently the energy supply for muscle
      cells. In this single-blind study, we compared the metabolic effects of atenolol
      with those of doxazosin, an alpha 1-blocker, during exercise in 26 young
      volunteers (age 20-35 years). All subjects performed an exercise test on a
      bicycle ergometer 5 h after consuming a standard breakfast. The starting workload
      of 50 W was increased by 30 W every 3 min until maximal heart rate (HR) was
      achieved; after a 2-min recovery period at 50 W the test was continued for 15 min
      at 60% maximal workload. Before and at the end of the test, blood samples were
      taken for glucose, lactate, and FFA determination. After 1 week, the test was
      repeated; the volunteers randomly received atenolol or doxazosin for 2 days
      before the second test. Exercise performance, plasma glucose, and lactate were
      not affected by either drug. The concentration of FFA was unchanged in subjects
      treated with doxazosin but was significantly reduced after the test in subjects
      treated with atenolol. Our data demonstrate that neither doxazosin nor atenolol
      impairs exercise performance in young volunteers. Atenolol reduces plasma FFA
      concentration possibly by inhibiting lipolysis. Doxazosin, in contrast, does not
      alter this parameter. Therefore, doxazosin may be a antihypertensive drug of
      potential benefit in treatment of hypertensive patients engaging in sports or
      undergoing a program of physical training.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723345
TI  - Antioxidative properties of histidine and its effect on myocardial injury during
      ischemia/reperfusion in isolated rat heart.
AB  - We wished to determine whether histidine scavenges hydroxyl radical, H2O2, and
      superoxide anion in vitro and to investigate the protective effect of histidine
      on isolated perfused rat hearts after global ischemia (40 min) and reperfusion
      (30 min) (I/R). Left ventricular (LV) function was recorded and coronary effluent
      was collected for measurement of lactate dehydrogenase (LDH) before ischemia and
      at 5, 10, 15, and 30 min of reperfusion. At the end of the experiment, a portion
      of the LV wall was fixed with 2% glutaraldehyde for morphological analysis; the
      remaining heart was immediately frozen in liquid nitrogen for determination of
      adenine nucleotides. Histidine effectively quenched hydroxyl radicals and H2O2,
      but not superoxide anions, in in vitro and in vivo conditions. Hearts treated
      with histidine exhibited significantly greater functional recovery during
      reperfusion as compared with nontreated hearts (p < 0.05). Cell morphology was
      well preserved, and enzyme release was significantly attenuated by histidine
      treatment (p < 0.05). Histidine raised the ATP level to 73% and the creatine
      phosphate level to 68% of normal control during reperfusion. Total adenine
      nucleotide pool and energy charge rate in histidine-treated hearts significantly
      increased as compared with those in nontreated hearts (p < 0.05), but no effect
      on ATP and creatine phosphate was noted during ischemia, Histidine prevents
      postischemic reperfusion injury in isolated heart by inhibiting reactive O2
      species and preserving high-energy phosphates (HEP).

PMID- 7723346
TI  - Effects of R56865, an Na(+)- and Ca(2+)-overload inhibitor, on myocardial injury
      in ischemic, reperfused porcine hearts.
AB  - The cardioprotective effect of R56865, an Na(+)- and Ca(2+)-overload inhibitor,
      was studied in 20 regionally ischemic reperfused (I/R) porcine hearts. Ten pigs
      were treated with a single intravenous (i.v.) injection of 0.4 mg/kg 15 min
      before occlusion of the distal left anterior descending coronary artery (LAD) for
      45 min. Ten other animals served as controls. Infarct size (IS) was determined as
      percentage of infarcted (tetrazolium method) to ischemic (dye technique)
      myocardium after 24-h reperfusion. Regional systolic shortening (SS) was
      determined by sonomicrometry. Fifteen minutes after i.v. administration of
      R56865, a significant decrease in heart rate (HR) (from 83 +/- 15 to 74 +/- 16
      beats/min), dP/dtmax (from 2,033 +/- 604 to 1,822 +/- 524 mm Hg/s), LAD blood
      flow (BF, from 17 +/- 7 to 14 +/- 7 ml/min), and calculated global myocardial O2
      consumption (MVO2) (from 5.9 +/- 0.9 to 5.4 +/- 0.9 ml O2/min x 100 g) was
      observed. Although this investigational drug attenuated the increase in HR during
      early reperfusion, the incidence of ventricular fibrillation (VF) was not
      affected during either ischemia or reperfusion. R56865 reduced IS by 24% from
      67.1 +/- 16% (control group) to 50.8 +/- 13%. In addition, this treatment
      improved systolic shortening after 24-h reperfusion from 6 +/- 8% (control group)
      to 15 +/- 9%. Our results support the concept that inhibition of intracellular
      Na(+)- and Ca(2+)-overload is a promising new principle in treatment of
      myocardial I/R.

PMID- 7723347
TI  - Defective stretch-induced release of atrial natriuretic peptide from aging
      hypertensive rat heart: possible role of phosphatidylinositol pathway.
AB  - Because the phosphatidylinositol pathway may be part of the signaling system
      associated with stretch-induced release of atrial natriuretic peptide (ANP), we
      tested the hypothesis that formation of the intermediate inositol-1,4,5
      trisphosphate (IP3) is impaired when ANP release is decreased in response to
      atrial stretch in hearts from aging genetically hypertensive (GH) rats.
      Immunoreactive ANP release into the coronary effluent and IP3 levels were studied
      in cardiac tissues of isolated perfused hearts from normotensive control (WAG) or
      GH rats aged 4, 11, or 16 months. Left atria were repeatedly distended and
      released with a latex balloon. ANP was measured in coronary effluent, and IP3 was
      measured in cardiac tissues. In all age groups, stretch and relief of stretch
      evoked considerably less ANP release in spontaneously beating hearts from GH than
      from WAG rats. Hearts from GH rats aged 16 months released no ANP, but electrical
      pacing restored some stretch-induced ANP secretion. With repeated stretch and
      release of stretch of the left atrium for 2 min, IP3 levels increased in left
      atrial tissue in WAG but not in GH hearts of all age groups. IP3 levels in
      (unstretched) left ventricles were much lower than in left atria and were
      unaltered by atrial stretch. In aging GH rats, the capacity to release ANP on
      atrial stretch is largely lost, in association with complete suppression of
      stimulus-induced increase in IP3 levels. These data support a role for IP3 in
      stretch-mediated atrial ANP secretion and suggest a progressive uncoupling of
      this signaling pathway in aging hypertensive rats.

PMID- 7723348
TI  - Pharmacological properties of KT3-671, a novel nonpeptide angiotensin II receptor
      antagonist.
AB  - We examined pharmacological profiles of KT3-671, 2-propyl-8-oxo-1-[(2'-(1H
      tetrazole-5-yl) biphenyl-4-yl)methyl]- 4,5,6,7-tetrahydro-cycloheptimidazole, a
      newly synthesized nonpeptide angiotensin II (AII) receptor antagonist in various
      in vitro and in vivo studies. KT3-671 displaced specific binding of [125I]Sar1
      Ile8-AII to AT1 receptor with a Ki value of 0.71 +/- 0.14 x 10(-9) M in rat liver
      membranes, but had no affinity for AT2 receptor in bovine cerebellar membranes
      (Ki > 10(-5) M). In isolated rabbit aorta, KT3-671 produced a parallel rightward
      shift in the concentration-response curve for AII with a pA2 value of 10.04 +/-
      0.12, but had no effect on KCl-, norepinephrine (NE)-, and serotonin (5-HT)
      induced contractions. In conscious normotensive rats, KT3-671 (0.3-10 mg/kg,
      p.o.) inhibited the AII-induced pressor response dose dependently. In renal
      artery-ligated hypertensive rats, KT3-671 (0.1-3 mg/kg, p.o.) decreased arterial
      blood pressure (BP) dose dependently. The hypotensive action of 3 mg/kg KT3-671
      was maintained for at least 24 h. These results suggest that KT3-671 is a potent
      AT1 subtype-selective and competitive nonpeptide AII receptor antagonist and has
      an orally active antihypertensive effect without agonistic activity.

PMID- 7723349
TI  - Regulation by taurine of the spontaneous activity in young embryonic chick
      cardiomyocytes.
AB  - Effects of taurine on the spontaneous action potential (AP) and the ionic
      currents in isolated 3-day-old embryonic chick ventricular cardiomyocytes were
      examined at different intracellular Ca2+ concentrations ([Ca]i) by whole-cell
      voltage-clamp and current-clamp methods. Experiments were performed at room
      temperature (22 degrees C). The firing rate of spontaneous activity was 61.2 +/-
      2.1 beats/min (n = 6) at pCa 10, and 68.2 +/- 1.8 beats/min (n = 6) at pCa 7.
      When [Ca]i was pCa 10, taurine 10 and 20 mM caused a positive chronotropic effect
      and enhanced the maximum rate of depolarization. In contrast, at pCa 7, taurine
      10 and 20 mM had a negative chronotropic effect. In voltage-clamp experiments,
      addition of taurine to the bath solution at pCa 7 inhibited the L-type Ca2+
      current (ICa(L)) and the delayed rectifying K+ current (IK). At pCa 10, both
      ICa(L) and IK currents were enhanced by taurine 10 and 20 mM. The voltage of half
      maximum inactivation for ICa(L) was not modified, nor was voltage of half-maximum
      activation for IK. These results indicate that taurine modulates the ICa(L) and
      IK currents dependent on [Ca]i, resulting in regulation of spontaneous activity.

PMID- 7723350
TI  - Terfenadine increases the QT interval in isolated guinea pig heart.
AB  - Torsades de pointes ventricular tachycardia (VT) has been reported in patients
      taking the nonsedating antihistamine, terfenadine. We performed
      electrophysiologic studies of 14 isolated guinea pig hearts using the Langendorff
      technique to assess whether terfenadine exerted actions that could be responsible
      for inducing the arrhythmia. Twelve hearts were perfused with an oxygenated
      Tyrode's solution containing a 2-microM preparation of either racemic, R-, or S
      terfenadine. QT interval (QT), monophasic action potential duration (APD), and
      ventricular effective refractory periods (ERP) were measured at a fixed range of
      cycle lengths (CL). At 400-ms CL, both isomers and racemate prolonged QT and APD
      by 8% and ERP was increased by 14%. Infusion of vehicle, dimethyl sulfoxide
      (DMSO), alone in two hearts caused a slight decrease in QT and APD, suggesting
      that the direct effect of terfenadine on QT may have been underestimated. One-way
      analysis of variance (ANOVA) showed no statistical difference in effect on QT,
      APD, or ERP for the three forms of terfenadine (p < 0.05). These results support
      the conclusion that terfenadine induces torsades de pointes because of direct
      actions in delaying cardiac repolarization. The lack of stereospecificity in this
      action indicates that chirally pure formulations are not likely to have greater
      safety than the racemate.

PMID- 7723351
TI  - Increase in plasma levels of adenosine and adenine nucleotides after intravenous
      infusion of buflomedil in humans.
AB  - To clarify the mode of action of the vasoactive agent buflomedil, we evaluated
      plasma levels of adenosine and adenine nucleotides after intravenous (i.v.)
      infusion in humans of 50, 100, and 200 mg of the drug in 20 min. Buflomedil
      induced an increase of the same order of magnitude in plasma levels of adenosine
      and adenine nucleotides. Maximal adenosine increase (84%) was observed at the end
      of the infusion period, whereas peak plasma levels of ATP and ADP (69 and 55%,
      respectively) and of AMP (61%) were detected 10 and 5 min after discontinuation
      of infusion, respectively. Although the exact mode of action of buflomedil at the
      molecular level remains unclear, some indirect findings suggest that the increase
      in adenosine may be due to enhanced release rather than to inhibition of cell
      uptake. Because such activity of buflomedil consists of enhancement of
      physiologic mechanisms of vasodilation and tissue protection occurring in the
      course of ischemic events, new pharmacologic perspectives for the drug may arise.

PMID- 7723352
TI  - Cardioprotective profile of the cardiac-selective ATP-sensitive potassium channel
      opener BMS-180448.
AB  - ATP-sensitive potassium channel (KATP) openers have direct protective effects on
      ischemic myocardium that are independent of vasorelaxation. Because reference
      KATP openers (e.g., cromakalim, pinacidil) are potent relaxants of smooth muscle,
      their utility for treating myocardial ischemia may be limited by hypotension.
      Efforts aimed at development of a cardioprotective KATP opener with less
      vasorelaxant activity led to identification of the arylcyanoguanidine analogue
      BMS-180448. In globally ischemic rat hearts, BMS-180448 was cardioprotective
      (EC25 for increasing time to contracture = 2.5 microM), with potency equal to
      that of cromakalim (EC25 = 4.9 microM) despite being significantly less potent as
      a peripheral smooth muscle relaxant (methoxamine-constricted rat aorta). The
      cardioprotective effects of BMS-180448 in isolated perfused rat heart were
      abolished by the KATP blockers glyburide and sodium 5-hydroxydecanoate,
      indicating KATP involvement in its mechanism of action. Further confirmation was
      obtained by demonstration of single KATP opening by BMS-180448 in guinea pig
      cardiac myocytes. In anesthetized dogs, cromakalim was > 100-fold more potent
      than BMS-180448 in decreasing blood pressure (BP). In anesthetized dogs subjected
      to 90-min coronary occlusion/reperfusion, BMS-180448 reduced infarct size (IS) by
      50% without hemodynamic effects. BMS-180448 provides the opportunity to explore
      the cardioprotective actions of this class of agents without the possible
      complications (hypotension, coronary steal) that may be caused by the currently
      available KATP openers.

PMID- 7723353
TI  - Cardiac refractoriness in rats is reduced by angiotensin II.
AB  - We investigated the effect of angiotensin II (AII) on cardiac refractoriness in
      muscle trabeculae isolated from adult rat ventricle. Strength-interval curves
      were initially obtained under control conditions and after exposure of the muscle
      to Tyrode's solution containing 10(-9) M AII. AII displaced the strength-interval
      curves to the left. The minimal current intensity needed to elicit a propagated
      response was reduced by AII for all intervals used. The effect of AII was not
      influenced by propranolol 10(-6) M or phentolamine 10(-7) M but was blocked by
      250 microM DuP 753. No change in resting potential was observed with 10(-9) M
      AII, but action potential duration at 50% APD50 of its amplitude was reduced by
      25% and conduction velocity was appreciably decreased (41%). The effect of the
      peptide on APD was blocked by DuP 753. Spontaneous discharges of APs were
      elicited by a single stimulus in fibers exposed to 10(-9) M AII, supporting the
      view that AII has an arrhythmogenic action.

PMID- 7723354
TI  - Different responses of renal blood flow and sympathetic nerve activity to
      captopril and nicardipine in conscious renal hypertensive rabbits.
AB  - To elucidate the roles of endogenous angiotensin II (AII) and renal sympathetic
      nerve activity (RSNA) in modulation of renal blood flow (RBF), we recorded RBF
      and RSNA in conscious two-kidney, one-clip (2K1C) hypertensive rabbits with blood
      pressure (BP) reduced to a similar extent by captopril (5 mg/kg) and nicardipine
      (4.3 micrograms/kg/min). We measured plasma concentrations of AII, arginine
      vasopressin (AVP), and norepinephrine (NE). Despite comparable depressor effects,
      changes in RBF showed different profiles with the two drugs in renal hypertensive
      rabbits. After captopril injection, RBF was consistently increased to 143 +/- 7%.
      In contrast, with nicardipine infusion, RBF was initially increased to 114 +/- 5%
      and then significantly decreased to 86 +/- 4%. The increase in RSNA was greater
      with captopril than with nicardipine. Plasma concentration of AII was decreased
      with captopril but significantly increased with nicardipine. In sham-clipped
      normotensive rabbits in which plasma AII was not increased, RBF was not reduced
      with nicardipine. Thus, vasoconstrictor actions of RSNA and increased AII may
      have overcome the vasodilatory effect of nicardipine in conscious renal
      hypertensive rabbits. Because the increase in RSNA was smaller with nicardipine,
      we speculate that the vasoconstriction induced by AII, as well as background BP
      level, played a substantial role in determining RBF.

PMID- 7723355
TI  - Differential responsiveness of atrial and ventricular myocytes to potassium
      channel openers.
AB  - We examined the effects of the potassium channel openers (PCOs) pinacidil and
      lemakalim (BRL 38227) on action potential (AP) configurations and outward
      currents in atrial and ventricular myocytes isolated from rabbit and guinea pig
      hearts, using the whole-cell configuration of the patch clamp technique at 33
      degrees-35 degrees C. The PCOs known to activate ATP-sensitive K+ current (IKATP)
      in various tissues, induced this current and decreased AP duration (APD) in
      rabbit ventricular myocytes. In contrast, in rabbit atrial myocytes, PCOs either
      had no effect or increased duration and plateau amplitude of the AP. The
      predominant outward current in rabbit atrial myocytes is a 4-aminopyridine (4-AP)
      sensitive transient outward current (Ito). The PCOs caused a decrease in Ito
      without inducing IKATP in rabbit atria. In identical experimental conditions,
      PCOs activated IKATP in both guinea pig atrial and ventricular myocytes. Our
      results suggest that (a) a species as well as cardiac tissue difference exists in
      responsiveness to PCOs, and (b) the decrease in Ito without concomitant induction
      of IKATP can lead to changes in AP configuration opposite to that expected from
      IKATP activation. Different effects of PCOs on distinct parts of the heart could
      lead to disparity in APD and refractoriness that may contribute to
      arrhythmogenesis.

PMID- 7723356
TI  - Effects of chronic angiotensin I-converting enzyme inhibition on the relations
      between ventricular action potential changes and myocardial hypertrophy in aging
      rats.
AB  - We studied the effect of aging on cardiac hypertrophy and action potential
      duration (APD) in normotensive male WAG/Rij rats and evaluated the role of the
      renin-angiotensin system (RAS) in these effects. Cardiac hypertrophy occurs in 30
      month-old rats, as indicated by an increase in heart weight, and APD gradually
      increases with aging in the epicardial region of the right and the left
      ventricle. Short-term treatment (1 month) with the angiotensin-converting enzyme
      inhibitor (ACEI) perindopril prevented age-related increase in heart weight/body
      weight ratio independent of its antihypertensive effects, but did not prevent
      changes in APD in 30-month-old rats. Our results show a dissociation of changes
      in cardiac mass from changes in APD during aging. The effect of ACEI on
      hypertrophy may be due in part to a direct angiotensin effect on cellular growth.
      Changes in APD are not related to hypertrophy but rather to the process of aging.

PMID- 7723357
TI  - Exploratory study of the effects of single doses of isomazole on hemodynamics and
      heart rate variability parameters in chronic heart failure.
AB  - Ventricular arrhythmias and disturbed autonomic control, as reflected by abnormal
      heart rate variability (HRV), are related to hemodynamic impairment in chronic
      heart failure (CHF). We investigated the effects of orally (p.o.) administered
      isomazole, a new phosphodiesterase (PDE) inhibitor with calcium-sensitizing
      properties, on hemodynamics, ventricular arrhythmias, and HRV and examined a
      possible interaction between these parameters. Hemodynamic measurements and
      ambulatory ECG monitoring were performed in 12 patients with stable CHF class III
      IV after single doses of isomazole 5-30 mg. Pulmonary wedge pressure decreased
      after 5, 10, 20, and 30 mg, but cardiac output, (CO) increased only after the
      higher doses [20 mg, + 20% (p = 0.031)] of isomazole. HR did not change. Mean
      arterial and pulmonary artery pressure, (MAP, PAP) decreased significantly in the
      10- and 20-mg groups [10 mg, -6% (p = 0.035) and -14% (p < 0.001) respectively;
      20 mg, -13% (p = 0.047) and -31% (p = 0.006), respectively]. Isomazole did not
      exert a significant effect on ventricular arrhythmias in the subsequent 24 h
      after acute dosing. Analysis of HRV showed that rMSSD and pNN50 (parameters of
      vagal tone) tended to increase after isomazole administration. Normalized high
      frequency power during the day increased from 17.4 to 22.3 nu (p < 0.05), whereas
      low frequency tended to decrease from 52.7 to 48.2 nu (p = 0.06). Acute isomazole
      administration improves hemodynamics but has no effect on ventricular
      arrhythmias. The HRV variability data suggest development of an increase in vagal
      control of HR, parallel to the acute hemodynamic improvement after isomazole.
      Withdrawal of vagal control of HR in CHF may be a reversible process.

PMID- 7723358
TI  - Does calcium channel blockade and beta-adrenergic blockade affect platelet
      function and fibrinolysis to a varying degree?
AB  - The effects of isradipine and atenolol on platelet function and fibrinolytic
      activity were studied in 10 male patients with mild untreated hypertension. After
      a 2-week placebo run-in period, the volunteers were randomized to either
      isradipine 2.5 mg twice daily or atenolol 100 mg daily for a 6-month period.
      Those initially receiving isradipine then received atenolol and vice versa. After
      each therapy regimen, blood was drawn at rest and 1 h after exercise during a
      maximum exercise test. Platelet activity in vivo was estimated as release of B-TG
      and PF-4. Fibrinolytic activity was estimated as the fast-acting inhibitor
      against tissue plasminogen activator usually termed PAI-1. During atenolol and
      isradipine therapy, blood pressure (BP) was equally reduced (p < 0.05). Heart
      rate (HR) decreased during atenolol treatment but was not changed by isradipine.
      Platelet activity in vivo estimated as B-TG and PF-4 decreased irrespective of
      therapy (p < 0.02). During atenolol, as during placebo therapy, exercise resulted
      in a significant increase in platelet activity, as shown by an increase in B-TG
      (p < 0.02) and in PF-4 (p < 0.01). Such increase was not observed during
      isradipine treatment. Both treatments tended to improve fibrinolysis, as shown by
      a decrease in PAI, 1 h after exercise. Reducing BP with isradipine or atenolol
      results in a similar decrease in platelet activity and PAI-level, tested at rest
      and 1 h after rest, respectively. During exercise, platelet activity increased
      during atenolol treatment; such change did not occur during isradipine treatment.

PMID- 7723359
TI  - Antithrombotic effect of ticlopidine on occlusive thrombi of small coronary
      arteries in (NZWxBXSB)F1 male mice with myocardial infarction and systemic lupus
      erythematosus.
AB  - We examined the antithrombotic effect of ticlopidine on occlusive thrombi of
      small coronary arteries in (NZWxBXSB)F1 [(WxB)F1] male mice with myocardial
      infarction (MI) and systemic lupus erythematosus (SLE). Ticlopidine (3 and 10
      mg/kg) was given to the mice as an additive to a standard laboratory diet from
      the time the mice were aged 16-24 weeks. The higher dose of ticlopidine
      significantly increased survival rate of the mice. In mice that received 10 mg/kg
      ticlopidine, the incidence of MI, the percentage of MI area (%MI), and the
      incidence and number of small coronary arteries with significant stenosis were
      significantly lower than in controls. The stenosed lesions were divided into
      occlusive thrombi related to acute MI and intimal thickening related to old MI.
      No mice had evidence of significant stenosis or thrombosis in the extramyocardial
      coronary arteries. Glomerulonephritis, blood urea nitrogen (BUN), and circulating
      immune complexes were not significantly different among the three groups. A high
      dose of ticlopidine prevented small coronary artery disease and MI and increased
      the survival of (WxB)F1 male mice, suggesting that this agent has an
      antithrombotic effect on occlusive thrombi of the small coronary arteries in such
      mice.

PMID- 7723360
TI  - Racial differences in beta-adrenoceptor-mediated responsiveness.
AB  - Previous studies have suggested that racial differences may exist in beta
      adrenoceptor-mediated responsiveness. However, no clear conclusions can be drawn
      based on these studies because of the confounding effect of the parasympathetic
      nervous system on responses to isoproterenol bolus doses. In this study, we
      blocked the effects of the parasympathetic nervous system with atropine, to
      determine whether racial differences exist in sensitivity to beta-adrenoreceptor
      stimulation and blockade. Sixteen healthy black and white men participated in the
      study. Atropine was administered before all studies to induce parasympathetic
      blockade. Isoproterenol sensitivity studies and treadmill exercise were then
      performed in the with and without beta-adrenoceptor blockade by propranolol.
      Responses measured included heart rate (HR), blood pressure (BP), and tremor. The
      average isoproterenol dose producing a 25-beat/min increase in HR was more than
      twofold higher in blacks than in whites (3.4 +/- 1.2 vs. 1.6 +/- 0.4 micrograms,
      respectively, p < 0.05). There were no racial differences in response to beta
      adrenoreceptor blockade. Our results showed that during parasympathetic blockade
      blacks were less sensitive to the chronotropic effects of isoproterenol than
      whites. We conclude that these response differences are due to greater beta
      adrenoceptor sensitivity in whites than in blacks.

PMID- 7723362
TI  - Laparoscopic colectomy for cancer.

PMID- 7723361
TI  - Ventricular overdrive pacing-induced preconditioning and no-flow ischemia-induced
      preconditioning in isolated working rat hearts.
AB  - To examine preconditioning induced by short periods of ventricular overdrive
      pacing (VOP) as compared with that induced by no-flow ischemia, we subjected
      isolated working rat heart to 10-min coronary artery occlusion (test ischemia)
      followed by 3-min reperfusion after three intermittent periods of VOP (10 Hz) or
      5-min no-flow ischemia, respectively. In the nonpreconditioned group, coronary
      occlusion decreased aortic flow (AF) from 46.6 +/- 2.4 to 13.7 +/- 1.7 ml/min and
      increased left ventricular end-diastolic pressure (LVEDP) from 0.53 +/- 0.05 to
      2.02 +/- 0.07 kPa. Preconditioning by VOP or no-flow ischemia significantly
      increased AF to 25.1 +/- 2.3 ml/min (p < 0.001) and to 27.3 +/- 1.4 ml/min (p <
      0.001) and decreased LVEDP to 1.38 +/- 0.1 kPa (p < 0.001) and to 1.65 +/- 0.05
      kPa (p < 0.05), respectively, after test ischemia. Glibenclamide 10(-7) M which
      blocked the anti-ischemic effect of the ATP-sensitive K(+)-channel (KATP) opener
      cromakalim, inhibited VOP-induced protection (AF 20.3 +/- 2.3 ml/min; LVEDP 1.82
      +/- 0.15 kPa), but did not affect no-flow ischemia-induced preconditioning [AF
      26.6 +/- 2.4 ml/min (p < 0.001), LVEDP 1.60 +/- 0.07 kPa (p < 0.01)]. VOP and no
      flow ischemia precondition heart, however their cardioprotective mechanisms may
      be different in terms of KATP activation in rats.

PMID- 7723363
TI  - Ex vivo activated memory T-lymphocytes as adoptive cellular therapy of human soft
      tissue sarcoma targets with potentiation by cis-diamminedichloroplatinum(II).
AB  - Autolymphocyte therapy (ALT) is tumor-specific, adoptive cellular therapy of
      neoplastic disease using nonspecific ex vivo activation of autologous peripheral
      blood lymphocytes (PBL), which are composed primarily of memory T-cells (ALT
      cells) and are active in patients with metastatic renal cell carcinoma and
      melanoma. Ex vivo pretreatment of tumor target cells with certain
      chemotherapeutic agents can enhance susceptibility to lysis by antitumor
      lymphocytes. To determine if cis-diamminedichloroplatinum(II) (CDDP) enhances ex
      vivo antitumor cytotoxicity of ALT-cells and if this lysis is mediated by T-
      and/or NK-cells and is human leukocyte antigen (HLA)-restricted, human soft
      tissue sarcoma (STS) target cells were derived from primary and metastatic
      surgical specimens and were incubated with and without CDDP. ALT-cells were
      prepared from autologous PBL obtained prior to surgery. Primary (PSTS) and
      metastatic (MSTS) target cells from each group were labelled with chromium 51
      (51Cr) and used as targets for ALT-cells, CD45-depleted ALT-cells, CD56 (NK)
      depleted ALT-cells, and PBL in a standard (4-hour) and delayed (18-hour) 51Cr
      release assay. Interferon-gamma (IFN-gamma) release was measured as an indication
      of antitumor effect and recognition by the noncytolytic lymphocytes in ALT-cells.
      Primary tumor target cells incubated in CDDP showed enhanced lysis as measured by
      the 51Cr release assay compared to non-CDDP-treated controls. Metastatic tumor
      target cells showed less lysis than the primary targets, although this was
      enhanced by pretreating metastatic tumor targets with CDDP. Lysis of all tumor
      targets was significantly greater when ALT-cells were used as the effector cells
      rather than PBL. Depletion of memory T-cells abrogated ex vivo lysis. Depletion
      of NK cells (CD56+) affected ex vivo lysis of autologous targets during the 4
      hour but not the 18-hour assay. Ex vivo ALT-cell lysis and IFN-gamma release
      against only the autologous tumor targets confirmed tumor-specificity in one
      patient. Restriction of ALT-cell lysis and IFN-gamma release against HLA-A2+
      autologous and one allogeneic HLA-A2+ STS tumor target, but not other non-STS
      targets, was demonstrated in another patient. These data suggest that CDDP may
      help render STS susceptible to tumor-specific, immune-mediated attack and that
      the combination of ALT and CDDP may lead to effective tumor-specific
      chemoimmunotherapy in patients with metastatic STS.

PMID- 7723364
TI  - Use of ileal urinary diversion in conjunction with intraoperative radiotherapy.
AB  - Intraoperative radiotherapy (IORT) was introduced in the 1970s as a new modality
      of cancer therapy. It has been especially useful after local irradiation or
      surgical failure. We report on the use of IORT in 13 patients with pelvic tumors
      requiring urinary diversion. All 13 were managed with ileal conduits. Despite the
      associated problems of prior abdominal procedures (11/13 patients), prior
      external beam radiation to the pelvis (11/13 patients), systemic chemotherapy
      (4/13 patients), and prolonged operative time (> 10 hours), perioperative
      mortality (1/13) and morbidity rates were low. We conclude that in cases of prior
      colonic resection and pelvic radiation, potentially irradiated ileum can be
      safely used for urinary diversion.

PMID- 7723365
TI  - Re-excision operations in nonpalpable breast cancer.
AB  - We retrospectively reviewed the records of 317 needle-localization (NL) biopsies
      performed at the Royal Marsden Hospital during 1989-1992. The malignancy yield in
      our centre, where there is an emphasis on cooperation with an experienced
      radiologist and breast pathologist, was 48% (151/317), with benign to malignant
      biopsy ratio of 1:1:1. Analysis of the histopathological findings of the
      malignant lesions revealed a 45% (68/51) incidence of positive microscopic
      margins. Of these 68 patients, 50 had re-excisions, including nine patients who
      required mastectomy. Twenty-eight of the re-excisions (56%) contained residual
      tumour, of which five (18%) were invasive carcinoma > 3 mm (size range 1-19 mm)
      and 13 (46%) were residual DCIS > 1 mm (size range 1-40 mm). Our findings suggest
      a significant incidence of residual disease associated with positive microscopic
      margins in NL-detected nonpalpable cancers. Therefore, our current practice of
      performing a wider re-excision for positive margins is justified. Stereotactic
      fine-needle aspiration cytology was not performed by the radiologist referring
      these cases, but it should be performed preoperatively and if the test is
      positive, definitive treatment in the form of wide local excision or
      quadrantectomy is carried out in the first instance in order to avoid a second
      surgical procedure.

PMID- 7723366
TI  - Needle localization breast biopsy: a model for multidisciplinary quality
      assurance.
AB  - As part of the quality assurance role of the Cancer Committee at Barnes Hospital,
      an institutional audit of Needle Localization Breast Biopsy (NLBB) was performed.
      Mammographic, operative, and surgical pathology reports from 370 consecutive
      patients at our institution undergoing both mammography and needle localization
      biopsy over a 34-month interval were reviewed. Carcinoma was diagnosed
      pathologically in 103 patients (28%), and 27% of these proved to be noninvasive.
      Sixteen patients were found to have histologic or clinical involvement of the
      axillary nodes; no patients with Tis lesions were found to have axillary nodal
      involvement. Of the patients, 73% were found to have either Stage 0 or Stage I
      disease, and 61% with an established malignancy had mastectomy (67% of patients
      with invasive carcinoma, 44% of those with carcinoma-in-situ), whereas 39% had
      some form of conservation therapy (33% of patients with invasive lesions, 56% of
      those with carcinoma-in-situ). Our results have been compared with other
      published studies, and important clinical indicators for evaluating the results
      of individual centers performing NLBB are discussed. It is concluded that NLBB is
      a safe and effective method of biopsying nonpalpable breast lesions, which allows
      for the identification of early stage breast carcinomas. In the present
      environment of concerns about the quality of care and costs, it is the
      responsibility of each center performing NLBB periodically to evaluate their
      results with this multidisciplinary procedure and to bring about change in those
      areas found to be deficient.

PMID- 7723367
TI  - Concomitant and isolated expression of TGF-alpha and EGF-R in human hepatoma
      cells supports the hypothesis of autocrine, paracrine, and endocrine growth of
      human hepatoma.
AB  - Single and double immunohistochemical staining for transforming growth factor
      (TGF)-alpha and epidermal growth factor-receptor (EGF-R) was done in order to
      identify the localization of TGF-alpha and EGF-R in human hepatocellular
      carcinoma (HCC). Single immunohistochemical staining for TGF-alpha showed
      immunoreactivity in the cytoplasm of hepatoma cells in 22 of 30 cases of HCC. The
      localization of TGF-alpha was heterogeneous from HCC cells to HCC cells. In the
      surrounding regenerative nodules, the hepatocytes were mildly to moderately
      positive for TGF-alpha. The proliferating bile ductules and peripheral nerves
      were also immunopositive for TGF-alpha. Single immunohistochemical staining for
      EGF-R demonstrated a linear localization of EGF-R along the cell membrane of the
      HCC cells in 21 of the 30 cases of HCC. In the regenerative nodules, the
      hepatocytes also showed linear staining along the cell membrane. Double staining
      for TGF-alpha and EGF-R in 12 cases of HCC showed a concurrent localization of
      TGF-alpha and EGF-R in some hepatoma cells and isolated localization of the two
      substances of other HCC cells. These combinations either abruptly moved around or
      intermingled with each other. These immunohistochemical results thus support the
      theory of an autocrine, paracrine, and endocrine mechanism of TGF-alpha and EGF-R
      on the proliferation of human hepatocellular carcinoma.

PMID- 7723368
TI  - Diagnosis and treatment of metachronous cancers in the esophagus and the head and
      neck region.
AB  - The esophagus and the head and neck region, both having the squamous epithelium,
      are thought to be subject to the same carcinogenic factors. This report discusses
      the diagnosis and treatment of secondary cancer detected following the treatment
      of primary cancer in 21 patients who had metachronous cancer comprising
      esophageal cancer and head and neck cancer. The secondary cancer was already
      advanced when detected despite the fact that almost all patients were followed up
      regularly at the outpatient clinic of the facility where the primary cancer was
      treated. Although surgical treatment of the secondary cancer was similar to that
      of the usual primary cancer, the prognosis for the former was poor, indicating
      that the prognosis tends to be determined by the disease stage of the secondary
      cancer. Early detection of the secondary cancer requires esophagoscopy using the
      iodine dye method or close examination of the head and neck region at an
      otolaryngologic outpatient clinic at the time of treatment of the primary cancer
      and thereafter at 6- to 12-month intervals.

PMID- 7723369
TI  - Adenomatous polyposis coli, protein kinases, protein tyrosine phosphatase: the
      effect of sulindac.
AB  - A putative explanation of the effect of sulindac on adenomatous colon and
      duodenal polyps from clinical observations and related in vitro experiments is
      presented. In cells with mutant APC genes, persistent high prostaglandin content
      of polyps leads to desensitization, downregulation of adenylate cyclase,
      uncoupling of cAMP synthesis from prostaglandin, and inactivation of protein
      kinase A (PKA). It is suggested that in normal cells, (APC) protein binds to
      catenins and microtubules to maintain structure and contribute to cell-cell
      communication, adherence, and the dephosphorylated state, a necessary condition
      for such functions. Cells with mutant APC product become isolated, deprived of
      communication and adhesion to other epithelial cells, overphosphorylated, and
      without corrective capability. The latter is largely due to downregulation of
      cAMP synthesis and protein kinase A activity secondary to high prostaglandin.
      Three main biochemical defects ensue: (1) the restrictive influence of PKA
      catalyzed phosphorylation of Raf-1 kinase and resultant effects on the MAP kinase
      cascade and transcription is lost, (2) the transcription of immediate early
      genes, including cyclooxygenase is stimulated, and (3) the stimulation of protein
      tyrosine phosphatase (PTPase) by PKA is in abeyance. These putative abnormalities
      are reversed by inhibition of cyclooxygenase-1 by sulindac. cAMP synthesis and
      PKA activity return to normal. PKA catalyzed phosphorylations block Raf-1 kinase
      at the confluence of the Ras and protein kinase C pathways. The MAP kinase
      cascade is inhibited as is transcription of immediate early genes. At the same
      time PKA stimulates PTPase, which dephosphorylates the cytoskeleton and restores
      cell-cell communication, adherence, and structure. The transformed phenotype is
      circumvented by adjustment of the phosphorylation state and mutant cells rejoin
      the epithelial community. The redox state of cytoplasm in mutant cells may be
      shifted toward reduction.

PMID- 7723370
TI  - Quantitative comparison of xenotransplantation of a human soft tissue sarcoma
      into the subcutaneous tissue of normal, postincision, and postincision plus
      indomethacin-treated nude mice.
AB  - The purpose of this study was to test the hypotheses that (1) surgical wounding
      can enhance the xenotransplantability of a human soft tissue sarcoma (HSTS26T)
      into subcutaneous (s.c.) tissue of nude mice, and (2) Indomethacin may reduce the
      xenotransplantability of this human tumor in the surgical wounding animal model
      by suppressing angiogenesis. The experimental method was to employ the
      quantitative transplantation assays (TD50, the number of tumor cells that, on
      average, would be expected to induce a tumor in 50% of the recipients). After an
      incisional wound (1.0-1.2 cm long) was made on the right leg of each experimental
      mouse, tumor cells were inoculated into the surgical wound, or into the
      contralateral leg at 24 and 72 hr postincision, and in another group tumor cells
      were inoculated into the wound at 72 hr postincision, plus daily s.c. injection
      of indomethacin, 2 mg/kg body weight for 8 consecutive days in a separate
      experiment. Nonincisional mice received the same inoculation as the control
      groups. The TD50s of surgically wounded groups were 3.5-10.7 times lower than
      that of the control groups. Significantly lower TD50 values were found in groups
      of cells inoculated into the surgical wound at 72 hr postincision (P < 0.05 or P
      < 0.01) and into the contralateral leg at 24 hr postincision (P = 0.05). No
      significant difference was found between the TD50 values in mice that received
      cells inoculated at 72 hr postincision plus indomethacin treatment, and those
      with no wound controls. Our conclusion is that the surgical wound can enhance the
      xenotransplantability of HSTS26T in nude mice. Indomethacin can decrease this
      enhancing effect level similar to that in no-wound controls and may prevent tumor
      recurrence in a surgical wound.

PMID- 7723371
TI  - Influence of lipiodolization on a cirrhotic liver.
AB  - Lipiodolization--selective regional cancer chemotherapy using Lipiodol plus an
      anticancer drug (LPD)--can prolong survival time of patients with an unresectable
      hepatocellular carcinoma (HCC). To enhance understanding of LPD's influence on
      the cirrhotic liver, we carried out related studies. Forty-three cirrhotic
      patients with HCC were treated with LPD (epirubicin in a dose of 15-40 mg/m2 and
      Lipiodol of 0.02-0.25 ml/kg). Seven cirrhotic patients with HCC were subjected to
      hepatic angiography alone, and these subjects selected randomly served as
      controls. Among the 43 treated with LPD, 23 belonged to Child's class A, 15 to
      class B, and 5 to class C. Blood samples were taken before angiography (pre) and
      at 24 hours after angiography (post) from each patient. Post/pre ratio of the
      following parameters were compared between patients of the two groups: sGOT,
      sGPT, and LDH as a marker for hepatocyte injury; t. bilirubin and hepaplastin
      test (HPT) as hepatocyte function; alkaline phosphatase and gamma-GTP to examine
      bile duct injury; and serum hyaluronic acid level to determine an endothelial
      cell functions. Post/pre ratio of serum GOT, GPT, LDH levels, and HPT in patients
      treated with vs. without LPD were 1.32 +/- 0.59 vs. 0.92 +/- 0.09 (P < 0.001),
      1.18 +/- 0.43 vs. 0.88 +/- 0.09 (P < 0.001), 1.11 +/- 0.20 vs. 1.00 +/- 0.07 (P <
      0.05), and 0.95 +/- 0.10 vs. 1.09 +/- 0.12 (P < 0.01), respectively. There were
      no significant differences in post/pre LPD ratio of other parameters, rates of
      complications, and hospital stay after LPD for patients with Child's class A, B,
      and C. Hepatocytes are apparently the primary site of injury in cases of LPD.
      LPDs, using epirubicin in a dose of 15-40 mg/m2 and Lipiodol in a dose of 0.02
      0.25 ml/kg, proved to be safe for cirrhotic patients with HCC.

PMID- 7723372
TI  - p53 correlates with improved survival in patients with esophageal adenocarcinoma.
AB  - Esophageal adenocarcinoma is a virulent malignancy that is rapidly increasing in
      incidence. Overexpression of p53, a tumor-suppressor gene with prognostic
      significance in many malignancies, has not been adequately evaluated in this
      disease. The purpose of this study was to evaluate the pattern and importance of
      p53 protein accumulation in patients with esophageal adenocarcinoma.
      Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded
      tissue from 24 patients, all of whom had early stage disease. Nineteen of 24
      patients underwent surgery, and 16 had complete tumor resection. p53 oncoprotein
      immunoreactivity was demonstrated in 50% (12/24) of patients overall and 50%
      (8/16) of patients undergoing esophagectomy. p53 overexpression was more common
      in patients with well-differentiated tumors (P = 0.07). The tissue surrounding
      tumor stained positive for p53 in six patients, four of whom had no evidence of
      Barrett's epithelium. Among the 16 patients who underwent esophagectomy, those
      whose tumors demonstrated p53 overexpression had a longer overall (28 vs. 13.5
      months) and disease-free (24.3 vs. 13 months) median survival. The difference in
      disease-free survival was significant (P = 0.05). Our findings suggest that p53
      overexpression may serve as a marker of improved survival in patients with
      esophageal adenocarcinoma.

PMID- 7723373
TI  - Family with nonmedullary thyroid neoplasms.
AB  - This report concerns a family in which papillary thyroid carcinoma appeared in
      the father and two daughters and follicular adenoma in a granddaughter. The
      father died of systemic metastasis of papillary thyroid carcinoma. The two
      daughters and granddaughter felt well postoperatively. We speculate that some
      gene-related factors might play an important role in familial occurrence of
      papillary thyroid carcinoma and follicular thyroid adenoma in the family.

PMID- 7723374
TI  - Needle track seeding after percutaneous ethanol injection therapy for small
      hepatocellular carcinoma.
AB  - We present two cases of patients experiencing needle track seeding after
      undergoing percutaneous ethanol injection therapy (PEIT) for small hepatocellular
      carcinoma, who were treated by surgical resection of the metastases. One patient
      demonstrated metastatic tumors due to needle track seeding 6 months after the
      beginning of PEIT (a total of 7 injection sessions for 2 tumors measuring < 20 mm
      in diameters), whereas the other developed a metastatic tumor 20 months after
      beginning PEIT (a total of 30 injection sessions for 3 tumors measuring < 20 mm
      in diameter). In the two cases, both the primary and metastatic tumors
      histologically revealed moderately differentiated hepatocellular carcinoma.
      Moreover, the histological findings of the metastatic foci did not always appear
      to be more aggressive than those of the primary tumors. Therefore, in order to
      detect such metastasis as early as possible, more careful attention should be
      paid to the appearance of needle track seeding after performing PEIT for
      hepatocellular carcinoma, even if the target of such PEIT is small HCC.

PMID- 7723375
TI  - Bile, bacteria, and gallbladder carcinogenesis.

PMID- 7723376
TI  - Overview of Microwave Applications in the Neurosciences.
AB  - This paper gives an overview of Microwave Applications in the Neurosciences and
      introduces this issue of the Journal of Neuroscience Methods. Emphasis is laid
      on: temperature, hotspots, hazards and cycle times in the use of the microwave
      oven. Consequences of the tissue dimensions and masking of antigens are
      discussed. Special problems encountered are: bulk preparation of specimens, brain
      electron microscopy, cooling of specimens during microwaving and the combination
      of microwave techniques. The recent developments discussed are vacuum-microwave
      application for large brain specimens and antigen retrieval.

PMID- 7723377
TI  - Programming the microwave oven.
AB  - Microwaves can be used to stimulate chemical bonding, diffusion of reagents into
      and out of the specimen, and coagulation processes in preparatory techniques.
      Temperature plays an important role in these processes. There are several ways of
      controlling the temperature of microwave-exposed tissue, fluids and solids that
      are used in these preparatory techniques. In this paper we describe our
      accumulated experience with monitoring and controlling microwave-oven parameters
      with the help of a personal computer (PC). A specially designed microwave oven
      was used with an advanced temperature probe. The oven was connected to an IBM
      compatible PC. This enabled us to analyze the quality of temperature control, and
      the relationship between displayed and actual temperature. We show that for
      microwave-transparent materials the addition of a microwave-absorbent plate to
      the material results in better temperature control.

PMID- 7723378
TI  - Preservation of myelinated fibers for electron microscopy: a qualitative
      comparison of aldehyde fixation, microwave stabilisation and other procedures all
      completed by osmication.
AB  - A qualitative comparison was made of a variety of electron microscopic
      preservation methods for nervous tissue, especially with respect to myelinated
      fiber areas. The methods studied were aldehyde perfusion/immersion fixation,
      aldehyde-tannic acid immersion fixation (stimulated by either microwave or
      conventional heating), microwave stabilisation, saline treatment with
      conventional heating (all with secondary osmication), and primary osmication. For
      all methods three morphological aspects, the ultrastructural quality of myelin
      sheath and axon and the coherence between the two were judged separately. It
      appears that the best version of each method studied is capable of providing a
      good overall ultrastructural result but always shows a preference for one or two
      of the three separate morphological aspects. When aiming at good axon quality
      together with good axon/myelin coherence, aldehyde perfusion/immersion, saline
      treatment or primary osmication are almost equivalent. Microwave stabilisation,
      on the other hand, can be chosen when good myelin quality has to be combined with
      good axon quality. For more specific purposes the following examples can be
      given. When excellent myelin quality is needed both microwave-stimulated aldehyde
      tannic acid fixation or microwave stabilisation can be considered. When the
      preservation of the axon quality has priority the aldehyde-perfused tissue should
      be further immersed in a heated aldehyde-tannic acid solution. Primary osmication
      guarantees excellent axon/myelin coherence. Despite the differences in detail, a
      remarkable correspondence is stressed between the overall results of sometimes
      extremely different methods of tissue preservation. Probably they all guarantee a
      reliable reflection of the in vivo situation. With respect to the use of
      microwave irradiation for tissue preservation, it appeared that stabilisation
      procedures are rather capricious. However, if successful, the results are not
      inferior to those of aldehyde fixation.

PMID- 7723379
TI  - Microwave applications on small insect brain tissue irradiated in a water
      perfused cooling-jacket for temperature control.
AB  - This paper describes a technique for microwave-accelerated fixation, washing and
      pre-embedding immunohistochemistry of insect brains. The temperature of the
      specimens is controlled with a water-cooling device. This device also serves as a
      permanent water load for microwave energy absorption and as a stirrer to avoid
      uneven energy distribution. The set-up described here allows continuous
      irradiation of specimens at full power, for unlimited time, without overheating.
      A considerable reduction in processing time could thus be achieved, along with
      improved immunolabelling.

PMID- 7723380
TI  - Effects of microwave pretreatment on immunocytochemical staining of vibratome
      sections and tissue blocks of human cerebral cortex stored in formaldehyde
      fixative for long periods.
AB  - The effects of the microwave antigen-retrieval method were investigated for five
      antibodies commonly used in neurosciences, i.e., Parvalbumin, Calbindin D28-K,
      MAP-2, MAP-5 and SMI-32. Immunocytochemical stainings were performed on free
      floating vibratome sections of tissue which had been stored in fixative for as
      long as 10 months to compare the effects of microwave treatment in one of the
      different metal solutions or in distilled water. Microwave treatment of free
      floating vibratome sections led to a severe wrinkling of the sections. Therefore
      the possibility of pretreatment of a thick tissue slice before vibratome
      sectioning was investigated. We conclude that microwave pretreatment of tissue
      slices in an aluminium chloride solution is the preferable antigen-retrieval
      procedure for the examined antibody staining when the immunocytochemical staining
      is lost or markedly reduced after storage in formaldehyde fixative for a long
      period. In particular SMI-32 and MAP-2, but also Parvalbumin staining, improved
      enormously after such a pretreatment.

PMID- 7723381
TI  - Application of microwave fixation techniques in pathology to neuroscience
      studies: a review.
AB  - The introduction of microwave energy into the scientist's repertoire of fixation
      modalities offers for the first time in relatively large specimens the potential
      for 'instantaneous' preservation of cellular structure for light and electron
      microscopy with minimal alteration of cellular biochemistry and antigenicity.
      Because of the rapid evolution of this new technology, we provide a
      classification system of newly generated microwave methods as applied to specimen
      preservation for microscopic analysis. With emphasis on neuronal tissue, we
      review qualitative and quantitative microscopy data of specimens fixed by two
      microwave methods in common use: (1) microwave stabilization and (2) fast and
      ultrafast, primary microwave-chemical fixation. In addition, we provide a table
      of neuropeptides or proteins in neuronal tissues that are preserved by various
      microwave fixation methods for histochemistry, immunohistochemistry, and immuno
      electron microscopy studies. Commercial microwave ovens have limitations which
      can result in irreproducible fixation results. Therefore, we present a
      calibration protocol that is used to identify the best locations for fixation
      within large cavity (i.e., household) microwave ovens. We also provide a
      standardization protocol to improve the reproducibility of microwave fixation in
      calibrated, large-cavity microwave ovens.

PMID- 7723382
TI  - Microwave technology in diagnostic neuropathology.
AB  - The microwave oven has a large range of potential applications in diagnostic
      neuropathology, ranging from tissue fixation and processing for light and
      electron microscopy to immunocytochemistry and molecular neuropathology. This
      review highlights the major current applications for the microwave oven and
      emphasises areas of particular recent interest. Established microwave techniques
      are discussed and suggested modifications to published staining techniques are
      included. Future potential diagnostic applications of microwave technology are
      emphasised, particularly in terms of in situ hybridisation and
      immunocytochemistry. Although many microwave techniques for use in diagnostic
      neuropathology are clearly established, widespread use of the microwave oven has
      not yet occurred in most neuropathology laboratories. The reasons for this
      apparent delay and some occasional difficulties in the use of the microwave oven
      are discussed. Increasing clinical demand for rapid diagnosis (particularly with
      the use of stereotactic brain biopsy techniques in providing tissue specimens for
      surgical neuropathology) will enable neuropathologists and laboratory technical
      staff alike to reconsider the use of the microwave oven for many laboratory
      techniques and reassess the wide range of potential applications and benefits
      that this useful tool has to offer.

PMID- 7723383
TI  - Studies of childhood brain tumors using immunohistochemistry and microwave
      technology: methodological considerations.
AB  - The immunohistochemical detection of antigens in archival tissue sections has
      been hampered by the poor reactivity of certain polypeptides in conventional
      formalin-fixed, paraffin-embedded material. For example, the poor reactivity of
      neurofilament proteins (NFPs) in surgical and autopsy specimens has been a major
      drawback of previous large, retrospective, clinicopathologic studies of pediatric
      primitive neuroectodermal tumors (PNETs), also known as medulloblastomas. We
      report our experience with a method of antigen retrieval which greatly enhanced
      the immunohistochemical detection of neuronal and glial intermediate filament
      proteins, retinal S-antigen (RSA), and the proliferating cell nuclear antigen
      (PCNA) in archival, paraffin-embedded, formalin or Bouin's-fixed, pediatric brain
      tumors, particularly PNETs. The technique involves adding a single brief step to
      an established avidin-biotin complex (ABC) immunohistochemical protocol
      (Vectastain Elite Kit). This step involves boiling tissue sections in distilled
      water for 5 min in a microwave oven. The specificity of staining was consistent
      with known cell and tissue specificities of the well-characterized monoclonal
      antibodies used and there was minimal background. Synaptophysin (SYN) staining
      was unaffected by heating and immunoreactivity of the low affinity nerve growth
      factor (p75NGFR) and the neural cell adhesion molecule (NCAM) were lost. The
      enhanced detection of neuronal and glial antigens in routinely prepared, formalin
      fixed, archival material should facilitate large retrospective clinicopathologic
      studies designed to assess the prognostic implications of differentiation in
      PNETs and to better understand the biology of these tumors.

PMID- 7723384
TI  - Hematopoietic growth factor receptors: structure variations and alternatives of
      receptor complex formation in normal hematopoiesis and in hematopoietic
      disorders.
AB  - Receptors of most hematopoietic growth factors are structurally related and
      grouped in the hematopoietin or cytokine receptor superfamily. In this paper, we
      will first review the general principles of hematopoietin receptor complex
      formation and cytoplasmic signaling. Subsequently, the significance of defective
      hematopoietic growth factor receptors for the development of hematological
      diseases will be discussed.

PMID- 7723385
TI  - A prospective evaluation of the roles of allogeneic marrow transplantation and
      low-dose monthly maintenance chemotherapy in the treatment of adult acute
      myelogenous leukemia (AML): a Southwest Oncology Group study.
AB  - Between February 1982 and December 1986, the Southwest Oncology Group conducted a
      prospective study in patients with newly diagnosed acute myeloid leukemia (AML)
      with two objectives: to evaluate the role of allogeneic marrow transplantation
      for patients in first remission, and to evaluate the role of low-dose monthly
      maintenance therapy in those patients not transplanted in first remission. Among
      522 evaluable patients, 295 (57%) achieved complete remission (CR), including 70%
      of patients age 49 or less. Twenty-four patients (15%) age 49 or less in CR were
      not HLA-typed, mostly because of financial constraints. HLA-identical donors were
      found for 39% of patients, of whom two-thirds were transplanted in first CR. The
      5-year disease-free survival among those transplanted in first CR, those with
      donors not transplanted in first CR, and those less than age 50 without donors
      was 41, 42, and 29%, respectively (P = 0.60). A total of 150 eligible patients
      were randomized to receive late intensification alone or late intensification
      plus monthly maintenance. In multivariate analyses, treatment with maintenance
      was associated with prolonged disease-free survival (P = 0.028), but not improved
      overall survival (P = 0.27). Factors associated with improved overall survival
      included younger age, lower white blood count (WBC) at diagnosis, having leukemia
      of M3 morphology, and being of white race. In this study, a diagnosis of M3 AML
      was particularly favorable, with disease-free and overall survivals of 75 and
      56%, respectively, at 7 years.

PMID- 7723386
TI  - Autologous bone marrow transplantation for acute myeloid leukaemia in children
      using total body irradiation and melphalan as conditioning regimen.
AB  - We conducted a phase II study on 19 children with AML in first (10 patients) or
      second (nine patients) complete remission (CR) treated with ABMT, evaluating the
      combination of total body irradiation (TBI, 12 Gy in six divided fractions) and
      high-dose melphalan (140 mg/m2 in single dose) in an attempt to improve
      antitumour efficacy of conditioning regimen. All patients received cryopreserved
      and in vitro purged (mafosfamide at a dose of 100 micrograms/ml) bone marrow. The
      median time from first CR to ABMT was 5 months compared with a median time of 3
      months for patients in second remission. One of the 19 patients, transplanted in
      second CR, died of transplant-related complication 10 days after transplant and
      another second CR patient relapsed on day +28, before engraftment. Three further
      patients in second CR relapsed at 6, 6 and 18 months after marrow transplant,
      respectively, and this determined a relapse rate of 43% in children given ABMT in
      second CR and 0% for patients transplanted in first remission (P < 0.05). Seventy
      two per cent of all patients are projected to be alive and disease-free at 6
      years, whereas the event-free survival of patients in first and in second CR is
      100 and 44%, respectively (P < 0.05). Although the number of patients does not
      allow us to draw any firm conclusion, our results are encouraging and suggest
      that the association of TBI and high-dose melphalan appears to be safe and
      valuable.

PMID- 7723387
TI  - Autologous bone marrow transplantation as consolidation therapy may prolong
      remission in newly diagnosed high-risk follicular lymphoma: a pilot study of 34
      cases.
AB  - We evaluated early intensification followed by autologous bone marrow
      transplantation (ABMT) using marrow purged by mafosfamide in patients with high
      risk low-grade follicular lymphoma (LGFL) reaching a status of minimal disease
      (MD). Thirty-four patients entered the program. All fulfilled at least one of the
      following criteria at diagnosis: a bulky tumor > 7 cm; three or more adenopathies
      > 3 cm; massive pleural or peritoneal effusion; massive splenomegaly; B symptoms;
      platelet count < 100 x 10(9)/l. Twenty-one patients had bone marrow involvement.
      Twenty-six patients received ACVBP, and eight CVP as front-line therapy. Twenty
      one (62%) patients achieved MD status, 18 reached intensification. At 4 years,
      the time to treatment failure is 55 +/- 9%, and the probability of persisting
      remission is 75 +/- 11%. Comparison by intention to treat of the 26 patients who
      received ACVBP as front-line therapy to 14 historical high-risk LGFL similarly
      treated in our institution without intensification, showed better results for the
      intensified group (P = 0.04 for both probability of persisting remission and time
      to treatment failure). These results indicate that early intensification using
      marrow purged with mafosfamide is a therapeutic option which may bring benefit to
      patients with high-risk LGFL.

PMID- 7723388
TI  - Differential TdT expression in acute leukemia by flow cytometry: a quantitative
      study.
AB  - Terminal deoxynucleotidyl transferase (TdT) has long been considered a diagnostic
      marker for acute lymphoblastic leukemia. Reports of TdT-positive cells in acute
      myeloid leukemia have lately questioned its diagnostic value. TDT has been
      detected mainly by microscopy methods: immunofluorescence and
      immunocytochemistry. The aim of this study was to reevaluate the diagnostic
      importance of TdT in acute leukemia by using flow cytometry with a method that
      allows quantitative analysis. Fifty-eight cases of acute leukemia were studied
      and TdT expression was quantified using calibrated fluorescent beads. The highest
      TdT values were found in B lineage acute lymphoblastic leukemia (ALL) while acute
      myeloid leukemia (AML) had the lowest values, even in cases with a high
      percentage of TdT-positive cells. Biphenotypic leukemia had intermediate values
      between B-lineage and T-lineage acute leukemia. The difference between these
      groups was statistically significant (P < 0.0001). The TdT assay by flow
      cytometry was more precise than immunocytochemistry because it recognizes
      quantitative differences between ALL and AML. It is also valuable in better
      defining the maturation stages in pre-B ALL and T-ALL. We conclude that
      quantitative flow cytometry of TdT re-establishes the diagnostic value of this
      enzyme and has potential applications for the study of minimal residual disease.

PMID- 7723390
TI  - Clinical significance of beta 2-microglobulin in serum of adult T cell leukemia.
AB  - To clarify the clinical and biological significance of beta 2-microglobulin (beta
      2-M) in serum of adult T cell leukemia (ATL) associated with human lymphotropic
      virus type-I (HTLV-I), beta 2-M was measured in 52 patients with ATL (acute ATL,
      35 patients; lymphoma ATL, two patients; chronic ATL, 12 patients; smoldering
      ATL, three patients), and it was compared with serum lactic dehydrogenase (LDH).
      Statistical analysis disclosed a correlation between beta 2-M level and the
      percentage of abnormal lymphocytes (P < 0.05) and platelet count (P < 0.01).
      There was a correlation between LDH and platelet count (P < 0.01), and a tendency
      of correlation between LDH and the percentage of abnormal lymphocytes (P < 0.15).
      Significant difference was present in beta 2-M as well as LDH between acute ATL
      and chronic ATL (P < 0.01), and between acute ATL and smoldering ATL (P < 0.01).
      We also investigated a significant inverse correlation between beta 2-M level as
      well as LDH level and the length of survival after the initial diagnosis (P <
      0.01). Thus, the beta 2-M level may indicate the aggressiveness of ATL cells and
      predict the length of survival.

PMID- 7723391
TI  - p53 gene mutation and loss of heterozygosity are associated with increased risk
      of disease progression in adult T cell leukemia.
AB  - Although the prototype of adult T cell leukemia (ATL) is an aggressive T cell
      neoplasm, ATL manifests four major clinical subtypes, acute, lymphoma, chronic,
      and smoldering. We studied the relationship between p53 gene alteration and
      clinical features in 34 patients with ATL, 14 acute type, 15 chronic type, and
      five crisis type transformed from chronic type. Using a polymerase chain
      reaction/single strand conformation polymorphism (PCR/SSCP) assay, followed by
      nucleotide sequencing, we detected mutations of the p53 gene in six of the 14
      acute type patients, two of the five crisis type, and one of the 15 chronic type
      patients. Gene dosage studies, using PCR amplification and Southern blotting,
      showed loss of heterozygosity (LOH) of the p53 gene in four of the 14 acute type
      patients, two of the five crisis type, and one of 14 chronic type patients
      examined. These observations indicated that the frequency of p53 gene alterations
      in the acute and crisis types of ATL was markedly higher than that in chronic
      type, suggesting that p53 gene alteration plays a role in the disease progression
      of ATL.

PMID- 7723389
TI  - Prognostic significance of the RT-PCR assay of PML-RARA transcripts in acute
      promyelocytic leukemia. The Leukemia Study Group of the Ministry of Health and
      Welfare (Kouseisho).
AB  - Minimal residual disease (MRD) was prospectively monitored at the 10(-5) level by
      the reverse transcriptase-polymerase chain reaction (RT-PCR) of PML-retinoic acid
      receptor alpha (RARA) transcripts from 27 acute promyelocytic leukemia (APL)
      patients who achieved complete remission (CR) with all-trans retinoic acid and
      chemotherapy (previously untreated patients, 15; refractory to chemotherapy or
      relapsed, 12). The RNA quality from bone marrow cells was firstly assessed by gel
      electrophoresis to avoid false negativity because of the fragility of the APL
      cells and the PML-RARA transcripts. In 12 of 15 untreated patients, RT-PCR became
      negative during consolidation and intensification therapy 4-16 months after the
      initiation of therapy, whereas it remained positive in nine of 12 refractory
      patients. At the end of therapy, RT-PCR was negative in 14 patients and positive
      in 13 patients. The former patients remained in CR at median follow-up of 9
      months after the end of therapy. In the latter, however, 10 patients relapsed at
      a median of 5 months after the end of therapy. These results suggest that the RT
      PCR assay can evaluate the quality of CR in APL and predict subsequent relapse.

PMID- 7723392
TI  - Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL).
AB  - Pancytopenia followed by a period of spontaneous recovery may precede the
      diagnosis of acute lymphoblastic leukemia (pre-ALL). Although both pre-ALL and
      myelodysplastic syndromes are preleukemic in a strictly temporal sense, there are
      several marked differences between the two conditions. We present eight children
      with pre-ALL who represented 2% of all cases of childhood ALL. The bone marrow
      was normo- or hypocellular with increased reticulin fibrosis during the pre-ALL
      phase. No cytogenetic abnormalities were found at the pre-ALL phase, but had
      developed at the time of overt leukemia in four of the six children examined.
      Based on the findings in our patients and on cases reported in the literature, we
      argue that pre-ALL is likely to represent a paraneoplastic syndrome early in the
      leukemic development that might be mediated via inhibitory properties related to
      clonally expanding but still cytogenetically normal cells. The findings may
      indicate a multistep pathogenesis of ALL.

PMID- 7723393
TI  - Localized gastric non-Hodgkin's lymphoma of high-grade malignancy in patients
      with pre-existing chronic lymphocytic leukemia or immunocytoma.
AB  - Analyses for clonality in cases of Richter's syndrome have provided evidence for
      a clonal evolution of high-grade lymphoma in most patients, while in others an
      independent cellular clone seems to exist in the secondary neoplasm. Richter's
      syndrome with an isolated high-grade lymphoma of the stomach has been rarely
      reported in patients with pre-existing B cell chronic lymphocytic leukemia (CLL).
      We investigated four cases of CLL or lymphoplasmacytoid immunocytoma (LPIC) with
      development of a localized high-grade B cell lymphoma in the stomach. Southern
      blotting showed different rearrangements of the immunoglobulin light and heavy
      chain genes in the tumor cells of the low-grade lymphoma and the gastric tumor in
      two cases. Comparison of the DNA sequences of the CDR3 region of the
      immunoglobulin genes revealed different clones in another case. By means of
      chromosomal in situ hybridization, trisomy 3 was detected in two cases of high
      grade lymphoma of the stomach, but not in the cells of the associated low-grade
      tumor. Our findings indicate that high-grade non-Hodgkin's lymphomas arising
      localized in the stomach of patients with CLL or immunocytoma are not clonally
      related to the pre-existing low-grade lymphoma and, therefore indeed, present
      true secondary neoplasms.

PMID- 7723394
TI  - Prospective monitoring of minimal residual disease during the course of
      chemotherapy in patients with acute lymphoblastic leukemia, and detection of
      contaminating tumor cells in peripheral blood stem cells for autotransplantation.
AB  - A prospective study for detecting minimal residual disease (MRD) was conducted on
      children with acute lymphoblastic leukemia (ALL). Thirty-nine patients (38 B
      lineage ALL, one T-ALL) with TCR delta rearrangements could be followed for 21 to
      44 months (mean 30.9 months) excluding four patients who died. One hundred and
      ninety four bone marrow (BM) samples and 13 peripheral blood stem cell (PBSC)
      grafts were available for detection of MRD. Initially 34 cases were treated
      prospectively according to the CCLSG risk-stratified protocols for ALL (ALL874 or
      ALL911), and five cases according to the other protocols. Conventional
      chemotherapy was replaced by autologous PBSC transplantation (PBSCT) in five
      patients, by allogenic BM transplantation (BMT) in one patient, or suspended in
      another patient. Twenty-nine of 32 children in whom conventional chemotherapy
      could be continued without interruption remain in complete remission (CR). In 24
      of the 29 patients MRD became undetectable within 12 months of their diagnosis.
      In five cases, BM samples obtained during maintenance therapy exhibited residual
      leukemia cells, and yet none of them relapsed (mean follow-up period 28.6
      months). Our results thus indicate that intensive maintenance therapy for
      patients with PCR-positive results during consolidation therapy may prevent
      subsequent relapse. Nine events of relapse were diagnosed in eight patients (five
      BM, two isolated central nervous system (CNS), one combined BM and CNS, one
      isolated skin relapse). An increase or a re-emergence of MRD was detected in BM
      samples obtained from patients prior to BM relapse, but one patient remained in
      CR despite reappearance of leukemic cells following a PCR-negative status.
      Monitoring of MRD failed to predict isolated CNS or skin relapse. PBSCT allows
      high-dose cytoreduction therapy for patients with refractory neoplasia. In our
      study, leukemic cells were identified in eight of 13 PBSC grafts harvested from
      five patients. Three of four children who received PBSC grafts containing
      leukemic cells relapsed within 6 months after PBSCT. Monitoring of MRD as part of
      quality control of PBSC grafts may ultimately contribute to improvements in PBSCT
      procedures.

PMID- 7723395
TI  - Correlation of bone marrow minimal residual disease and apparent isolated
      extramedullary relapse in childhood acute lymphoblastic leukaemia.
AB  - We have used a polymerase chain reaction (PCR) technique capable of detecting one
      leukaemic cell in 10(5) normal cells to monitor minimal residual disease (MRD) in
      a retrospective study of childhood ALL. We were particularly interested in
      comparing MRD findings in patients in long-term remission, bone marrow relapse
      and apparent isolated extramedullary relapse (EMR). Archival slides were
      initially studied from 21 patients. However, on subsequent analysis, only 15
      patients were informative at the molecular level. All seven patients with EMR had
      evidence of MRD in the bone marrow at the time of relapse. Five of the seven also
      had evidence of bone marrow MRD prior to EMR. In one of the seven patients, MRD
      was not detected in a bone marrow sample studied 5 months prior to EMR. The
      remaining EMR patient was not studied prior to EMR. Of five patients who remained
      in long-term remission (mean 144 months), three did not have detectable MRD at
      the end of induction therapy (2 months) and all five were MRD-negative at the end
      of treatment (36 months). This contrasts with the three patients who relapsed in
      the bone marrow at 8, 15 and 88 months post-treatment and who had evidence of MRD
      at the end of therapy.

PMID- 7723396
TI  - The relationship between secondary chromosomal abnormalities and blast
      transformation in chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) is a stem cell disorder which progresses from
      a chronic phase (CP) to an accelerated phase (AP), and/or a blast phase (BP) of
      myeloid (M) or lymphoid (L) phenotype. This progression is frequently preceded or
      accompanied by recurring secondary chromosomal abnormalities which are believed
      to play a role in the transformation. In order to investigate the relationship
      between the secondary change and the development of BP, we undertook a study
      using fluorescence in situ hybridization to determine in which cells the
      secondary abnormalities were present. We observed that in one case of L-BP, the
      secondary change (trisomy 8) appeared to be in a subclone that was different from
      the blast cells, as it was absent from the lymphoblasts but present in
      differentiating erythroid, monocytic and granulocytic cells. In two cases, the
      secondary change (trisomy 8, extra Ph) probably occurred prior to an acute
      transforming event as it was present in CP or AP predominantly in differentiated
      granulocytic or monocytic cells. In one case of M-BP, the secondary change
      (trisomy 8) probably occurred after the acute transformation, as it appeared in
      only a subset of the blasts. Lastly, in four cases of L-BP, the secondary change
      (monosomy 7, extra Ph or hyperdiploidy) was closely associated with the BP as it
      was present in all of the blasts. The findings indicate that some secondary
      abnormalities may be directly related to the development of BP and may provide
      clues to the identity of genes responsible for the acute phase transition. Other
      abnormalities occurring before, or after the acute transformation or in a
      different subclone from the acute phase blasts, may be more important for
      denoting genomic instability than for helping to understand the mechanism of
      blast transformation.

PMID- 7723397
TI  - Jumping translocations in leukemia.
AB  - Jumping translocations are an unusual phenomenon and have been rarely reported in
      leukemia. We report three patients whose leukemic cells had multiple related
      clones resulting from unbalanced jumping translocations of 1q and 7q to
      chromosomes 1, 8, 15, 21 and 22. The chromosome findings, together with limited
      published reports, suggest that jumping translocations are new non-random
      rearrangements and may represent poor prognostic biological markers. Although
      their origin is unknown, circumstantial evidence suggests that telomeric ends of
      receptor chromosomes may play a role in stabilizing jumping translocations in
      dividing malignant cells.

PMID- 7723398
TI  - Late appearance of a Philadelphia translocation with minor-BCR/ABL transcript in
      a t(7;11)(p15;p15) acute myeloid leukemia.
AB  - We describe a patient with a t(7;11)(p15;p15) acute myeloid leukemia who was
      subsequently found to harbor the Philadelphia (Ph) translocation, in addition to
      the t(7;11), at the second relapse. A BCR/ABL transcript was detected at the
      second relapse by reverse transcription-polymerase chain reaction assay; the
      leukemic cells had a BCR/ABL fusion gene involving the minor breakpoint cluster
      region (minor-BCR; situated in intron 1 of the BCR gene). Although the Ph
      translocation is commonly detected in de novo acute leukemia and chronic myeloid
      leukemia as the primary leukemia-specific chromosomal translocation, our case
      suggests that this cytogenetic change might occur as an additional chromosomal
      change in neoplastic cells. Moreover, minor-BCR/ABL rearrangements may also occur
      as a late appearance of Ph translocation.

PMID- 7723399
TI  - Sequence preservation of the third exon of the bcl-2 gene in non-Hodgkin's
      lymphoma: absence of somatic hypermutation.
AB  - The t(14;18) translocation juxtaposes the bcl-2 gene on chromosome 18 to a
      joining (J) gene segment of the immunoglobulin heavy chain gene (IgH) on
      chromosome 14. Up to 85% of non-Hodgkin's lymphomas (NHL) are t(14;18) positive.
      Recent reports have documented point mutations in the second exon of translocated
      bcl-2 alleles and postulated that immunoglobulin variable (V) region somatic
      hypermutation, related to Ig sequences approximately 250 Kb downstream, may be
      mediating these mutations. We have examined the third exon of bcl-2, directly
      adjacent to Ig sequences in the t(14;18), for point mutations. In particular, we
      studied the translated region of exon 3 in 45 NHLs by SSCP analysis and failed to
      detect a single point mutation. Further, we sequenced eleven t(14;18)
      breakpoints, including both bcl-2 and JH sequences, and detected only one point
      mutation, in a JH-derived sequence. We conclude that immunoglobulin V region
      somatic hypermutation does not induce point mutations into the t(14;18)
      breakpoint region or into the translated region of the third exon of bcl-2
      alleles involved in the t(14;18) translocation, conserving the membrane insertion
      properties of the carboxyl tail of this protein.

PMID- 7723400
TI  - Detection of p53 mutations in B cell non-Hodgkin's lymphoma cell lines.
AB  - The p53 tumor suppressor gene is frequently mutated within its evolutionarily
      conserved regions in a number of human cancers. Previous reports demonstrated
      mutations of this gene in both Burkitt's lymphoma and B cell chronic lymphocytic
      leukemia. However, dissimilar results were obtained in non-Hodgkin's lymphoma
      (NHL). In one study, no mutation was detected in 43 NHL tissues. A second study
      reported p53 mutations in eight (all with advanced stage disease) out of 48
      tissues obtained from Japanese NHL patients. Using both immunoblotting and radio
      immunoprecipitation, we detected mutant p53 proteins in nine out of 10 B cell
      lines established from NHL tissues. The mutations were confirmed by reverse
      transcription polymerase chain reaction-mediated single-strand conformational
      polymorphism (RT-PCR-SSCP) analysis in eight cell lines. The high frequency of
      p53 mutation in NHL B cell lines and the relatively low frequency of p53
      mutations in fresh lymphoma tissue suggests that p53 gene alteration may play a
      role in lymphomagenesis and/or disease progression in a subset of B cell
      lymphomas and that the p53 mutation conveys a proliferative advantage on lymphoma
      cells that permits their in vitro growth.

PMID- 7723401
TI  - Presentation of a PCR-nuclease protection strategy for minimal residual disease
      monitoring in B-ALL.
AB  - Methods for detecting residual malignant cells in patients suffering from
      lymphoid malignancies have neither been sufficiently sensitive nor easy to
      routinize, hampering a potential prediction of disease outcome. Taking advantage
      of clone-specific DNA sequences, generated during lymphocyte differentiation and
      the polymerase chain reaction, some strategies have been developed for several
      groups. Up to now the most specific and sensitive methodology, which consists of
      designing leukemia-specific oligonucleotides, requires sequencing of the
      complementary determining region III-DNA for each particular patient and is too
      laborious to be applied to each case for routine monitoring in most hospital
      laboratories. In an attempt to achieve an easy way to detect residual malignant
      cells in B lymphoproliferative diseases, we have used a new PCR-based approach,
      named here as PCR-nuclease protection assay, consisting of: (i) amplification of
      DNA segments corresponding to the complementarity determining region III of the
      immunoglobulin heavy chain genes from samples at disease diagnosis; (ii)
      isolation of the disease-specific single-stranded DNA; (iii) labeling of the
      single-stranded DNA to generate specific probes; (iv) hybridization to amplified
      DNA from samples corresponding to different disease phases; and (v) digestion
      with S1-nuclease. Using this approach, we could detect one malignant cell in a
      background of 10(5) healthy cells. The sensitivity and specificity of this
      approach compares with those of the above mentioned specific oligonucleotide
      strategy in detecting residual malignant B cells. Moreover, this strategy is much
      less tedious and could be used by most hospital laboratories.

PMID- 7723402
TI  - In vivo effect of human granulocyte-macrophage colony-stimulating factor (GM-CSF)
      on neutrophil GM-CSF receptors.
AB  - The effect of in vivo administration of recombinant human granulocyte-macrophage
      colony-stimulating factor (rhGM-CSF) on neutrophils GM-CSF receptor, was
      investigated in patients with neoplastic diseases and normal hematopoiesis.
      Patients were divided into two groups. Group A received a single dose of rhGM-CSF
      (5 micrograms/kg/day) and receptor studies were performed 90 min and 48 h after
      treatment. Group B received three doses, administered subcutaneously every 24 h
      and receptor studies were performed 90 min after first injection and 24 h after
      the last. Before treatment neutrophils only displayed high-affinity receptors (KD
      85 +/- 53 pM; number of receptors/cell 1318 +/- 567). The first injection of rhGM
      CSF produced a transient leucopenia and the internalization of GM-CSF receptor on
      neutrophils in both groups of patients: 90 min after s.c. administration
      receptors could not be detected with conventional binding studies. In group A
      patients, 48 h after a single dose of rhGM-CSF, receptors, albeit with a
      decreased affinity (KD = 240 +/- 131 pM; number of receptors/cell 783 +/- 494)
      were again expressed. In group B patients, 24 h after the last rhGM-CSF
      injection, low intermediate affinity receptors not present before treatment
      appeared (KD 720 +/- 175 pM; number of receptor/cell 1222 +/- 179). They were
      associated with a low number of high affinity receptors (KD = 9 +/- 4 pM; number
      of receptors/cell 106 +/- 44). These observations indicate that more than one
      type of GM-CSF receptor may exist on neutrophils. It may be suggested that in
      vivo the regulation of the GM-CSF receptor is different from that in vitro and is
      related to the presence of the cytokine in patient blood.

PMID- 7723403
TI  - GM-CSF enhances IL-2-activated natural killer cell lysis of clonogenic AML cells
      by upregulating target cell expression of ICAM-1.
AB  - Acute myeloid leukemia (AML) cells express the surface adhesion proteins
      intercellular adhesion molecule-1 (ICAM-1, CD54) and lymphocyte function
      associated molecule-3 (LFA-3, CD58). Exposure to the myeloid growth-promoting
      cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulates
      expression of ICAM-1 and LFA-3 on AML cells but does not increase their
      sensitivity to lysis by interleukin-2-activated natural killer cells (LAK) in
      51Cr assays. However when AML cells are exposed to GM-CSF prior to incubation
      with LAK, their subsequent clonogenic activity is significantly reduced. If a
      blocking antibody to ICAM-1 is added during the incubation period of AML with
      LAK, the inhibitory effect is completely ablated. A less pronounced effect is
      observed with an antibody to LFA-3. ICAM-1 is expressed on a greater proportion
      of CD34+ than CD34- AML cells and exposure to GM-CSF induces a significantly
      greater upregulation of ICAM-1 on leukemic CD34+ cells than their CD34-
      counterparts. These data suggest that the inhibitory effect of IL-2-activated
      natural killer cells on clonogenic AML cells is mediated principally via the
      lymphocyte function associated molecule-1 (LFA-1)/ICAM-1 interaction. Interleukin
      2 upregulates LFA-1 expression on natural killer cells. Simultaneous
      administration of effector cell activators such as IL-2 and target cell
      modulators such as GM-CSF may have a therapeutic benefit in patients with minimal
      residual myeloid leukemia.

PMID- 7723404
TI  - Interferon-gamma inhibits apoptosis induced by wild-type p53, cytotoxic anti
      cancer agents and viability factor deprivation in myeloid cells.
AB  - Different hematopoietic cytokines including colony-stimulating factors and
      interleukins can inhibit apoptotic cell death induced in myeloid cells by the
      tumor-suppressor gene wild-type 53 and a variety of cytotoxic anti-cancer agents.
      In this study we identity interferon-gamma as an anti-apoptotic cytokine for
      myeloid cells in which apoptosis was induced by wild-type p53, cytotoxic anti
      cancer agents or viability factor deprivation. The inhibition of wild-type p53
      mediated apoptosis in myeloid leukemic cells by interferon-gamma was not
      associated with downregulated expression of wild-type p53 or the p53-induced
      cyclin-dependent kinase inhibitor gene WAF-1, or with upregulated expression of
      the apoptosis-inhibiting gene bcl-2. Interferon-gamma also inhibited induction of
      apoptosis by a p53-independent pathway. Interferon-gamma inhibited apoptotic cell
      death caused by withdrawal of viability factors in normal myeloid precursor
      cells, the interleukin 3-dependent 32D cell line and differentiating myeloid
      leukemic cells. Interferon-alpha/beta did not inhibit apoptotic cell death in any
      of these systems. The results indicate that although interferon-gamma can inhibit
      cell multiplication and differentiation in myeloid cells, it shares with other
      hematopoietic cytokines the ability to protect normal and leukemic myeloid cells
      from induction of apoptosis.

PMID- 7723405
TI  - Exposure to occupational and environmental factors in myelodysplastic syndromes.
      Preliminary results of a case-control study.
AB  - We performed a case-control study of occupational and environmental risk factors
      in myelodysplastic syndromes (MDS) diagnosed at our institution, using the method
      of Siemiatycki. A control for each MDS case, matched for age, sex, and residence
      area was chosen. The questionnaire asked demographic data, medical history, and
      information on life-time environmental and occupational exposures. Occupational
      exposures were first assessed by job titles, then by evaluating exposure to a
      list of 70 chemicals, and the level and duration of exposure to those chemicals
      (exposure index). In the first 100 cases and controls analyzed, a significantly
      higher incidence of smokers or ex-smokers was seen in MDS cases (odds ratio, OR =
      1.83, P = 0.03). A significant excess of MDS was found in male patients with jobs
      (or previous jobs) generally exposing to chemical compounds, including plant and
      machine operators and assemblers (odds ratio, OR = 3.73, P = 0.014) whereas, on
      the contrary, technicians and associate professionals were more often seen in
      controls (OR = 0.17, P = 0.002). In males, there was also a trend for more
      skilled agricultural workers and coal miners in MDS cases. In females, there was
      a non-significant trend for more professionals in controls. After adjusting for
      sex, age and smoking habits, significantly more frequent exposure to stone dusts
      (OR = 3.06, P = 0.011), and cereal dusts (OR = 2.27, P = 0.04) was found. There
      was also a trend for higher incidence of exposure to exhaust gases and nitro
      organic explosives. In addition, significantly higher exposure indices to petrol
      and diesel derivatives (P = 0.03) and to fertilizers (P = 0.003) were seen in MDS
      cases, as compared to controls. No significant difference in exposure to other
      chemicals was seen between MDS cases and controls. These preliminary results of
      our study, which is accruing more cases, suggest, as two previously published
      case-control studies of risk factors in MDS, that exposure to some chemicals may
      be involved in the pathogenesis of MDS.

PMID- 7723406
TI  - Perturbations of multiple hemopoietic lineages in retrovirus-induced murine
      malignant histiocytosis.
AB  - A fatal systemic proliferation of malignant histiocytes resembling human
      malignant histiocytosis was induced in susceptible mice following infection with
      the murine retrovirus malignant histiocytosis sarcoma virus (MHSV). It is shown
      that MHSV additionally caused profound alterations of erythropoiesis,
      granulocytopoiesis and thrombocytopoiesis, and in the hemopoietic stem cell
      compartment. In the erythroid lineage, MHSV induced a normocytic peripheral
      anemia, which was paralleled by an unphysiologic, multifocal clonal expansion of
      erythroid blasts in the spleen. These cells were not transformed and appeared to
      have a maturation defect since blood reticulocytes did not increase above control
      values. Moreover, MHSV exerted cytopathic effects on neutrophilic granulocytes
      and megakaryocytes, since their numbers transiently decreased in the spleen, and
      agranulocytosis and thrombocytopenia was observed in the blood. Nonetheless,
      regeneration was found in both lineages at later stages of the infection, which
      was accompanied by a terminal granulocytosis. The number of lineage-committed and
      multipotential colony-forming cells in the CFU-S assay increased transiently, but
      decreased to very low levels in the final stages of the disease. Thus, the
      studies demonstrate that the same etiologic agent, MHSV, had different effects on
      hemopoietic cells, which included malignant transformation, hyperproliferative
      and cytopathic effects.

PMID- 7723407
TI  - Establishment of a novel myeloma cell line KPMM2 carrying t(3;14)(q21;q32), which
      proliferates specifically in response to interleukin-6 through an autocrine
      mechanism.
AB  - We established a new human myeloma cell line, KPMM2, which proliferates
      specifically in response to IL-6 via an autocrine mechanism. The proliferative
      response of KPMM2 cells to exogenous IL-6 was significantly stimulated in a dose
      dependent manner. The growth was markedly inhibited by an anti-IL-6 mAb and an
      anti-IL-6 receptor (IL-6R) mAb in a dose-dependent manner. KPMM2 cells expressed
      IL-6 and IL-6R mRNA by RT-PCR. Flow cytometric analysis showed cell surface
      expression of IL-6R. IL-6 protein was detected in the culture supernatant by
      ELISA. IL-11, oncostatin M and leukemia inhibitory factor had no effect on the
      proliferation of KPMM2 cells although interferon-alpha and interferon-gamma
      inhibited the growth. Furthermore, KPMM2 cells bore a t(3;14)(q21;q32)
      translocation and this finding is of potential interest for future studies in the
      light of the nuclear protein BM28 (CDCL1, for cdc-like 1) mapped on 3q21, which
      plays an important role in the cell cycle. In this report, we demonstrated
      completely an IL-6-dependent autocrine growth mechanism in KPMM2 cell line. This
      cell line may be useful to investigate the pathogenesis of multiple myeloma and
      to evaluate the therapeutic potential of IL-6 blocking agents in vitro and in
      vivo.

PMID- 7723408
TI  - Rapid synthesis of hybrid RNA molecules associated with leukemia-specific
      chromosomal translocations.
AB  - A number of gene arrangements have been described as characteristic abnormalities
      associated with different types of leukemia, and this list is still growing. In
      view of the biological, clinical and prognostic relevance of the pathological
      fusion products, techniques permitting their detection are of paramount
      importance in the clinical setting. In some instances, permanent leukemic cell
      lines carrying the abnormality of interest are available for the establishment
      and standardization of molecular assays. For a number of newly discovered gene
      rearrangements, however, this may not be the case. It is therefore of great
      interest for clinical laboratories to have alternative technical possibilities
      for the set-up of standardized molecular tests. This problem provided the
      stimulus to design a simple and rapid method for in vitro generation of chimeric
      RNA molecules corresponding to pathological fusion transcripts typical for
      chromosomal translocations in leukemias. Two separate fragments are generated in
      a four-primer multiplex PCR. Due to a PCR-generated overlap, a chimeric fragment
      can be synthesized in a second round of PCR. This PCR product is then purified
      with the help of magnetic beads. Due to the SP6 promotor sequence incorporated
      during the second round of PCR, transcription into RNA is easily facilitated
      while the template DNA is still bound to the solid phase. Following this strategy
      we were able to synthesize the fusion transcripts m-BCR/ABL, CBF beta/MYH11, and
      MLL/AFp1 which are the molecular equivalents of t(9;22)(q34,q11), inv16(p13;q22)
      and t(1;11)(p32;q23), respectively. The chimeric RNA will be useful as a control
      template in diagnostic RT-PCR strategies. It can also be further processed in
      translation systems leading to the corresponding chimeric oncoprotein. This
      approach can be easily used to create any hybrid RNA of interest.

PMID- 7723409
TI  - A case of acute megakaryoblastic leukaemia with t(X;6)(p11.21;q23) having an X
      chromosome breakpoint within a 450-Kb region which is also disrupted in two
      classes of solid tumours.
AB  - Karyotype analysis of a case of acute megakaryoblastic leukaemia revealed an X;6
      translocation as the sole abnormality. Using fluorescence in situ hybridisation
      on leukaemic metaphases we demonstrated that the breakpoint on the X-chromosome
      occurred at p11.21, within a region spanned by a YAC probe which has also been
      found to be disrupted in synovial sarcomas and some papillary renal cell
      carcinomas.

PMID- 7723410
TI  - bcl-2 expression in myelodysplastic syndromes and its correlation with
      hematological features, p53 mutations and prognosis.
AB  - We looked for bcl-2 protein expression by immunocytochemistry on bone marrow
      slides from 51 cases of myelodysplastic syndrome (MDS), of whom 25 received some
      form of chemotherapy. Forty-six of them had at least 20% bcl-2 positive blasts
      and the median percentage of positive blasts was 80%, whereas myeloid cells
      beyond blasts were always negative. No correlation was found between bcl-2
      expression and the FAB type of MDS, CD34 expression and P-glycoprotein
      expression. A strong correlation between weak bcl-2 expression and the presence
      of a p53 mutation detected by SSCP analysis and direct sequencing was found.
      Response to chemotherapy (intensive chemotherapy or low-dose Ara-C) and survival
      were not significantly influenced by the intensity of bcl-2 expression in blasts,
      although there was a trend for better response to chemotherapy and longer
      survival in patients with strong bcl-2 expression. This trend was no longer
      found, however, if patients with a p53 mutation were excluded. Our findings show
      that blasts from a majority of MDS cases have bcl-2 expression and that strong
      bcl-2 expression is not associated with a poor prognosis. The correlation between
      weak bcl-2 expression and p53 mutation suggests a possible downregulation of bcl
      2 gene expression by mutated p53, the mechanism of which remains to be
      established.

PMID- 7723411
TI  - Association of myelodysplastic syndrome and relapsing polychondritis: further
      evidence.
AB  - We report five patients with both a myelodysplastic syndrome (MDS) and relapsing
      polychondritis (RP), that represented 0.6% of all MDS and 28% of all RP diagnosed
      over a period of 14 years. Ten other cases had previously been reported (four in
      detail), supporting a non-fortuitous association between the two disorders,
      already suggested for MDS and some other immunological disorders.

PMID- 7723412
TI  - Balanced parental contribution to the ABL component of the BCR-ABL gene in
      chronic myeloid leukemia.
AB  - Genomic imprinting has recently been associated with the reciprocal t(9;22)
      chromosome translocation of chronic myeloid leukaemia (CML). This translocation
      gives rise to a 22q-, or Philadelphia (Ph), chromosome and a derivative 9q+.
      Based on heterochromatin polymorphisms, it was reported that the former is of
      maternal and the latter of paternal origin in every case of CML. This parental
      bias led to the hypothesis that the genes disrupted by the translocation, BCR and
      ABL, were themselves imprinted, and that in CML the BCR-ABL gene was formed by
      BCR sequences of maternal and ABL sequences of paternal origin. We have
      identified a BstNl restriction fragment length polymorphism in the ABL coding
      sequence which enabled us to investigate directly the expression and inheritance
      of the two ABL alleles in heterozygous CML patients. Amplification of the
      specific BCR-ABL and normal ABL mRNA messages by reverse transcriptase-polymerase
      chain reaction in these patients showed that the ABL moiety of the BCR-ABL gene
      has an even chance of being the paternal or the maternal copy. We conclude
      therefore that there is no parental bias in the origin of the translocated ABL
      gene and no evidence for genomic imprinting of ABL in CML.

PMID- 7723413
TI  - Are ABL and BCR imprinted? No definitive answers, but more questions.
AB  - The apparent nonrandom contribution of the paternally-derived chromosome 9 and
      the maternally-derived chromosome 22 to the leukemia-specific translocation
      t(9;22)(q34;q11) obtained by cytogenetic analysis suggested that the two genes
      affected by this rearrangement, namely ABL and BCR, are imprinted. The results of
      recent molecular genetic studies have challenged this notion, since it was shown
      that both the paternal as well as the maternal BCR- and ABL-alleles may be
      affected by the translocation event and that both genes may be expressed from
      both alleles. This paper offers possible explanations for the apparent
      contradictory results obtained through cytogenetic and molecular genetic means.
      Based on the few available data concerning their allelic methylation pattern,
      replication behavior and expression status, as well as by referring to similar
      problems encountered in other genes whose imprinting status had also remained
      elusive for a long time, I argue that it still remains likely that ABL and BCR
      are imprinted.

PMID- 7723414
TI  - Standpoint on imprinting of BCR and ABL.
AB  - Cytogenetic studies of Ph-positive leukemic patients and their parents have
      indicated that chromosome 22 involved in the formation of the t(9;22) is of
      maternal origin, whereas chromosome 9 is preferentially of paternal origin. These
      data have suggested that the two genes BCR and ABL, which become fused through
      the translocation, might be imprinted, ie expressed in a parental-specific
      manner. Recent molecular genetic studies however, have shown that BCR and ABL are
      expressed on both alleles and that the maternal and paternal ABL genes contribute
      equally often to the BCR-ABL fusion messenger. The findings make imprinting of
      these genes unlikely as an explanatory model and necessitate a combined
      cytogenetic and molecular genetic study.

PMID- 7723415
TI  - The parental origin of the Philadelphia chromosome: evidence of additional,
      recurring recombinatorial events.

PMID- 7723416
TI  - Biosensors: a viable monitoring technology?
AB  - Biosensors for practical in vivo and in vitro applications are dependent on the
      effective integration of several biological and physical technologies. This
      review paper was stimulated by an IEE seminar. Some of the more recent advances
      aimed at taking techniques of fundamental and academic interest to various forms
      of practical reagentless biochemical analysis are highlighted, with associated
      clinical and commercial consequences. The paper describes some of the most recent
      developments in biosensor research, in particular those relating to material
      aspects of fabrication, including multilayer films for sensor applications,
      advances in ISFETs, conjugated polymers, new developments in quartz crystal based
      biosensors, as well as advances in amperometric enzyme electrodes and the
      application of devices for continuous monitoring.

PMID- 7723417
TI  - Application of an artificial neural network to the control of an active external
      orthosis of the lower limb.
AB  - The object of this paper is to present a real-time application of an artificial
      neural network (ANN). The application for which this network is demonstrated is a
      motorised orthosis with six degrees-of-freedom for use by a paraplegic; a
      'walking machine'. Theoretical networks and training methods need modification to
      function correctly with a real application. Several complex phenomena that are
      very difficult to model have to be accommodated; the starting threshold of the
      activators, non-linearity, noise, and the non-biunivocity between successive
      system states (position, velocity, actuator controls). The modifications made to
      the network and the associated training method partially alleviate these
      difficulties.

PMID- 7723418
TI  - Artificial neural networks for the diagnosis of atrial fibrillation.
AB  - Different forms of artificial intelligence have been applied to pattern
      recognition in medicine. Recently, however, a relatively new technique involving
      software-based neural networks has become more readily available. Deterministic
      logic is currently applied to rhythm analysis in computer-assisted ECG
      interpretation methods developed in the University of Glasgow. The aim of the
      present study is to compare an artificial neural network with deterministic logic
      for separating sinus rhythm (SR) with supraventricular extrasystoles (SVEs)
      and/or ventricular extra-systoles (VEs) from atrial fibrillation (AF) at a
      particular point in the diagnostic logic of the Glasgow Program. A total of 2363
      ECGs with 1495 AF and 868 SR + (SVEs and/or VEs) are used for training and
      testing a variety of neural networks, and the optimum design is selected. Methods
      for combining the results of the neural-network classification and the
      deterministic interpretation are also developed. A further 717 ECGs are used to
      test the selected network. The results show that the use of an artificial neural
      network can improve the sensitivity of reporting AF from 88.5% using the
      deterministic approach to 92%, without sacrificing specificity (92.3%).

PMID- 7723419
TI  - On-line respiratory artefact removal via adaptive FIR filters in
      rheopneumographic measurement.
AB  - Impedance rheopneumography is a simple non-invasive technique that can reflect
      the vascular condition in the human pulmonary circulatory system. However, the
      much larger and almost in-banding respiratory artefact present has greatly
      restricted its usefulness to only respiratory patients of a less severe type, in
      view of the existing practice of requiring the subject to stop breathing
      momentarily during measurement. Conventional fixed or adaptive filtering cannot
      satisfactorily remove the artefact in view of the non-time stationary
      characteristic of the latter. In the paper, a fast adaptive FIR filter design
      method, which is based on the filter coefficient look-up table (CLT) concept, is
      presented as a solution. The CLT is constructed with the coefficients indexed to
      the cut-off frequency to separate the two components of the plethysmogram. An on
      line fast Fourier transform is calculated to track the cut-off frequency. This
      filter can adaptively change its coefficients, not only for different subjects,
      but also for the same subject during long-term monitoring. Results show that this
      filter design is capable of providing an almost respiratory artefact-free signal
      for a majority of patients. The high speed of implementation also renders it a
      possibility for real-time monitoring applications.

PMID- 7723420
TI  - Corrected formula for estimating peripheral blood flow by impedance
      plethysmography.
AB  - In this paper, the limitations of the conventional formula for the computation of
      peripheral blood flow from impedance plethysmograms are highlighted, and a
      correction to the formula is suggested. A conductivity cell experiment is
      described to show the dependence of the value of the blood flow index (BFI),
      obtained from the conventional formula, on the mean resistivity of the cell. It
      is also shown that the value of the corrected BFI is independent of the mean
      resistivity. Anomalies observed in the amplitude of systolic waves in impedance
      plethysmograms of patients with oedema are explained.

PMID- 7723421
TI  - Dynamic description of stochastic signal by adaptive momentary power and
      momentary frequency estimation and its application in analysis of biological
      signals.
AB  - The importance of dynamic spectral analysis of time-varying signals in medicine,
      biology and technology is increasing rapidly. The basic spectral parameters are
      momentary power and momentary frequency. The paper presents adaptive recursive
      estimation methods for these spectral parameters. Their specific properties are
      investigated, and the possibilities of applications in computer-assisted analysis
      of biological and technical signals are demonstrated, even satisfying real-time
      requirements.

PMID- 7723422
TI  - Measurements of closing force of surgical wounds and relation to the appearance
      of resultant scars.

PMID- 7723423
TI  - Radio-frequency ring applicator: energy distributions measured in the CDRH
      phantom.
AB  - SAR distributions were measured in the CDRH phantom, a 1 cm fat-equivalent shell
      filled with an abdomen-equivalent liquid (sigma = 0.4-1.0 S m-1; dimensions 22 x
      32 x 57 cm) to demonstrate the feasibility of the ring applicator to obtain deep
      heating. The ring electrodes were fixed in a PVC tube; diameter 48 cm, ring width
      20 cm and gap width between both rings 31.6 cm. Radio-frequency energy was fed to
      the electrodes at eight points. The medium between the electrodes and the phantom
      was deionised water. The SAR distribution in the liquid tissue volume was
      obtained by a scanning E-field probe measuring the E-field in all three
      directions. With equal amplitude and phase applied to all feeding points, a
      uniform SAR distribution was measured in the central cross-section at 30 MHz.
      With RF energy supplied to only four adjacent feeding points (others were
      connected to a 50 omega load), the feasibility to perform amplitude steering was
      demonstrated; SAR values above 50% of the maximum SAR were measured in one
      quadrant only. SAR distributions obtained at 70 MHz showed an improved focusing
      ability; a maximum at the centre exists for an electric conductivity of the
      abdomen-equivalent tissue of 0.6 and 0.4 S m-1.

PMID- 7723425
TI  - Magnetohydrodynamic effects on blood flow through a porous channel.

PMID- 7723424
TI  - Statistical relationships between systolic blood pressure and heart rate and
      their functional significance in conscious rats.

PMID- 7723426
TI  - Analysis of non-linearity of optical oxygen sensors based upon phosphorescence
      lifetime quenching.

PMID- 7723428
TI  - Multichannel bacterial growth analyser by impedance and turbidity.

PMID- 7723427
TI  - In-house management of diagnostic imaging equipment.

PMID- 7723430
TI  - Low-power ECG amplifier/detector for dry-electrode heart rate monitoring.

PMID- 7723429
TI  - Variable convergence adaptive filter and its application to cardiac action
      potentials.

PMID- 7723431
TI  - Bio-impedance active electrode for in vivo measurement.

PMID- 7723432
TI  - Real-time processing of ultrasonic Doppler signals of fetal activity.

PMID- 7723433
TI  - Lung sound crackle analysis using generalised time-frequency representations.

PMID- 7723434
TI  - Surface EMG muscular conduction velocity measurement system implemented on a
      standard personal computer without A/D convertor.

PMID- 7723435
TI  - Integrated unit for programmable control of the 21F Hemopump and registration of
      physiological signals.

PMID- 7723436
TI  - Frequency synthesis of digital filters based on repeatedly applied unweighed
      moving average operations.
AB  - Simple formulae are presented for designing filters based on repeatedly applied
      moving average operations with unit coefficients. Design formulae are derived to
      synthesise the filter in a way that satisfies specified passband and stopband
      specifications. These filters are attractive because of the reasonable frequency
      characteristics, the computational efficiency of the design and filter
      algorithms, and the uncomplicated implementation in software.

PMID- 7723437
TI  - Detection of early atherosclerosis by analysis of ultrasonic Doppler signals
      produced by mural flow disturbances.
AB  - The paper describes an in vitro study using a multi-gate Doppler ultrasound
      system to investigate flow disturbances in a blood analogue caused by small
      stenoses (2-25% cross-sectional area reduction), using steady flow (100-600 ml
      min-1) in a 6 mm diameter rigid artery model. The results indicate that stenoses
      greater than 5% were detectable.

PMID- 7723438
TI  - The proceedings of the Conference of Measuring the Effects of Medical Treatment.
      Minneapolis, Minnesota, April 21-22, 1994. Dedicated to Marilyn Bergner.

PMID- 7723439
TI  - Measuring the effects of medical interventions.
AB  - This article reviews a number of important issues in selecting health-related
      quality-of-life measures in studies of the effects of medical interventions.
      Concerning the selection of domains, a plea is made for a greater use of
      qualitative discovery methods than is currently the case. It is also argued that
      measures of specific outcomes are inadequate to describe fully the effects of
      medical interventions, and must be coupled with more general outcome measures.
      Concerning the selection of measures, an argument is made that psychometric
      evaluation should be less concerned with the internal consistency reliability of
      short outcome measures and more with the ability of short-form measures to
      reproduce total scale variance. It is also noted that precision of measurement
      has been a neglected topic in the psychometric evaluation of outcome measures in
      this area of research. Future work should consider precision within the range of
      the outcome where effects are expected much more seriously. Finally, future
      methodologic work is called for using methods based on item response theory to
      study precision and bias.

PMID- 7723440
TI  - Comparison of generic versus disease-specific measures of functional impairment
      in patients with cataract.
AB  - The increased demand for health status measures in evaluating medical
      interventions has increased the importance of clarifying when to use generic
      versus disease-specific health status measures. The authors compared the
      performance of a well known generic health status measure, the Sickness Impact
      Profile (SIP), and a disease-specific measure of functional impairment related to
      vision (the VF-14) in detecting functional impairment in 426 cataract patients
      before and at 12 months after first eye cataract surgery. Using analysis of
      covariance models, the associations were assessed between the SIP and VF-14 and
      four criterion variables--patient ratings of trouble and satisfaction with their
      vision and overall health, and best corrected visual acuity--after controlling
      for patient age and medical comorbidities. Preoperative patient ratings of
      trouble and satisfaction with vision were significantly associated with VF-14
      scores (P < 0.001), but not with SIP scores. Preoperative visual acuity in the
      better eye was significantly associated with both VF-14 and SIP scores (P <
      0.001). Patient general health ratings were significantly associated with SIP
      scores (P < 0.001), but not with VF-14 scores. Postoperative changes in patient
      ratings of their vision and in visual acuity were significantly associated with
      changes in VF-14 scores (P < 0.05), but not with changes in SIP scores. Changes
      in patient ratings of overall health were significantly associated with changes
      in SIP scores (P < 0.01), but not with changes in VF-14 scores. In patients
      undergoing cataract surgery, a disease-specific health status measure is more
      sensitive to preoperative functional impairment related to vision, and to change
      in functional impairment after cataract surgery, than is a generic health status
      measure.

PMID- 7723441
TI  - Comparison of a generic and a disease-specific measure of pain and physical
      function after knee replacement surgery.
AB  - Generic and disease-specific health status instruments are commonly used to
      assess patients' outcomes. The hypothesis that they measure distinct but
      complementary aspects of patients' quality of life was tested using a sample of
      patients aged 67 to 99 years who had undergone knee replacement surgery 2 to 7
      years previously. Patients' scores on a generic health-related quality-of-life
      (HRQOL) measure, the SF-36, were compared to those of the Western Ontario and
      McMaster Universities (WOMAC) Osteoarthritis Index; the WOMAC was developed
      specifically for patients with lower extremity arthritis, whereas the SF-36 is
      aimed at all conditions. A stratified sample of 1,750 Medicare beneficiaries was
      surveyed and an overall response rate of 80.3% achieved, resulting in 1,193
      usable surveys (after adjustment for ineligible, incapacitated, and deceased
      individuals). The distribution of scores on the three dimensions common to both
      instruments (i.e., pain, physical function, and overall score) showed
      consistently higher scores on the WOMAC, on a scale of 0 (worst) to 100 (best),
      than on the SF-36, indicating less disability from arthritis than from other
      conditions after knee surgery in this elderly population. Statistically
      significant differences in the number of people with perfectly healthy scores
      were detected between the instruments; with regard to pain, 32.2% of the sample
      reported no pain due to arthritis on the WOMAC, compared with only 13.6%
      reporting no pain due to any conditions on the SF-36. The figures for physical
      function and overall score were 9.6% versus 1.4%, and 6.9% versus 0.2%,
      respectively. Examination for discriminant validity showed that the scores on the
      two scales followed hypothesized patterns: the WOMAC discriminated better among
      subjects with varying severity of knee problems, whereas the SF-36 discriminated
      better among subjects with varying levels of self-reported health status and
      comorbidity. The results of this study support the inclusion of both a generic
      and a disease-specific HRQOL measure to assess patient outcomes fully.

PMID- 7723442
TI  - Comparison of health-related quality of life in clinical trial and nonclinical
      trial human immunodeficiency virus-infected cohorts.
AB  - Clinical trials randomly assign treatments and select participants to maximize
      internal validity, but such selection threatens generalizability by excluding
      important groups with the diseases under study. Particularly in human
      immunodeficiency virus (HIV) disease, the results of clinical trials are applied
      broadly to populations, despite limited representation by minorities and
      disadvantaged groups. Health-related quality of life (HRQOL), which is
      increasingly recognized as an important outcome in these studies, may be
      sensitive to differences that affect generalization of trial results to target
      populations. This study compared HRQOL in two HIV-infected cohorts: 1)
      multicenter AIDS Clinical Group Trials in which most subjects are white,
      privately insured, and high-income (n = 1,907); and 2) a study of ethnically
      diverse, low-income patients recruited from public clinics (n = 205). Both
      studies included 30 HRQOL items developed in the Medical Outcomes Study (MOS) and
      items on symptoms, medications, and demographic characteristics. HRQOL scores
      were significantly lower in the nontrial sample (P < 0.001) by about one standard
      deviation, even after direct adjustment for clinical and demographic
      characteristics, and also after comparison of the nontrial sample with the most
      symptomatic in the trial sample. The relationships of characteristics with HRQOL
      differed between nontrial and trial samples, suggesting problems generalizing
      results from HIV clinical trials to important target populations. HRQOL measures
      such as those from the MOS can be useful in detecting differences that affect
      generalization.

PMID- 7723443
TI  - A comparison of alternative ways of measuring fatigue among patients having
      hysterectomy.
AB  - In a study of the outcomes of hysterectomy, 1,205 patients rated their fatigue
      levels via three single-item measures and the Profile of Mood States (POMS)
      Fatigue Scale. The single-item fatigue measures asked patients to indicate how
      often they were tired during the day, how often feeling tired had prevented them
      from doing what they wanted to do, and how big a problem feeling tired was for
      them. All four measures of fatigue were found to be correlated with pain,
      activity limitation, and psychological dysfunction, although the POMS Fatigue
      Scale was more strongly related to psychological dysfunction than the other
      fatigue measures. All four measures indicated substantial relief from fatigue 6
      months after hysterectomy among the participants in this study. Patients who
      remained or became fatigued by 6 months posthysterectomy had more physician
      contacts than those not fatigued, and were less satisfied with the results of the
      surgery. Fatigue was found to be a useful outcome measure of medical treatment.
      Each of the fatigue measures examined provided unique and useful information,
      with no one fatigue measure proving to be substantially superior to the others.

PMID- 7723444
TI  - Including deaths when measuring health status over time.
AB  - Measuring health status over time is problematic when some subjects die, because
      death does not have a defined value on most health status measures. This
      situation is different from the usual missing data problem because the health
      status of the dead is, in a sense, known. We examined eight strategies for
      incorporating deaths into such analyses using three health status measures taken
      from two data sets, after which we used computer simulation to explore more fully
      the effect of deaths. The strategies differed in the amount of influence given to
      the deaths, varying from none (deaths were discarded) to complete (mortality
      itself was the health measure). The strategies that gave less influence to deaths
      tended to show more favorable changes in health over time, and therefore, tended
      to favor the group that had more deaths. The strategies that were more influenced
      by death showed more negative changes over time and favored the group with fewer
      deaths. The choice of strategy should depend on the goals of an intervention. For
      health promotion studies, we recommend recoding the health variables to estimate
      the probability that a person will be healthy in 2 years (or in some other period
      that can be estimated from the data).

PMID- 7723445
TI  - Change in clinical status, health status, and health utility outcomes in HIV
      infected patients.
AB  - Psychometric health status scales and health utility scales were compared to
      measure the impact of changes in clinical status in patients infected with the
      human immunodeficiency virus (HIV). The data used included the first two waves of
      a longitudinal study of 160 HIV-infected patients, a population that was 34%
      women and 65% African American. The Medical Outcome Study-HIV Health Survey (MOS
      HIV); sleep, cognitive function, and depression scales; the Sickness Impact
      Profile Home Management Scale; and questions on HIV-related clinical symptoms
      were administered. Standard gamble utilities and categorical rating scale
      preferences were assessed for current health state. The MOS-HIV scale scores of
      asymptomatic patients were significantly higher than those of symptomatic
      patients and patients with acquired immune deficiency syndrome. No differences
      were observed for utilities. Increases in clinical symptoms over 4 months were
      associated with changes in health perception, pain, physical role function,
      social function, mental health, depression, energy, cognitive function, and
      categorical rating scale preferences. The MOS-HIV and other health status
      measures discriminated between HIV disease stages and were associated with
      clinical status. Standard gamble utilities did not discriminate among the three
      groups and were not correlated with clinical status.

PMID- 7723446
TI  - A comparison of various methods of collecting self-reported health outcomes data
      among low-income and minority patients.
AB  - In a randomized trial of different data collection methods, we challenged the
      untested assumption that reliable data cannot be obtained from lower-income
      and/or minority patients by self-administered questionnaires. We tested three
      methods of data collection among a sample of lower-income and minority patients
      (n = 697) in Indianapolis at a site for the Type II Diabetes Patient Outcomes
      Research Team. The study included a questionnaire literacy screening instrument
      to assess patients' functional literacy. Based on their functional literacy,
      patients were randomized to one of three methods of data collection: mail
      out/mail-back, hand-out/assisted, or the in-home interview. We constructed a
      tiered system for reassigning nonresponders to alternative methods of data
      collection, using the in-home interview as the fall-back strategy. We compared
      the response rates, item completion rates, and internal consistency reliabilities
      of self-reported health status measures between patients with and without
      literacy limitations and across the three methods of data collection. Patients
      with and without literacy limitations, across methods of data collection,
      provided high-quality data, as evidenced by high item completion rates (> 84%)
      and high reliability assessments (internal consistency reliability coefficients >
      .80) for each health status measure. As part of the tiered study design,
      nonresponders randomized to either the mail-out/mail-back or the hand
      out/assisted method were interviewed. These patients were significantly older,
      had significantly lower education and income levels, and had significantly poorer
      self-reported visual function as compared with those who responded to the
      originally assigned method. We conclude that expensive, labor-intensive data
      collection methods, such as in-home interviews, are not necessary for many low
      income, minority patients to generate high-quality, reliable health status data.
      Using appropriate screening instruments, those patient subgroups needing special
      help can be screening instruments, those patient subgroups needing special help
      can be identified and targeted for more expensive data collection methods. This
      tiered approach has policy implications for the cost, feasibility, and quality of
      data collection in health outcomes research.

PMID- 7723448
TI  - Choosing questions that people can understand and answer.

PMID- 7723447
TI  - Estimating the value of a generic quality-of-life measure.
AB  - In this paper, data from a clinical trial of a new antiviral agent for treating
      patients with zoster are used to answer the following question: Does the
      Nottingham Health Profile (NHP) add to the information obtained from the clinical
      measures? Three ways in which the NHP could add information are measured. First,
      Cox's regression analysis is used to determine whether health-related quality-of
      life scores obtained at diagnosis give information about disease prognosis.
      Second, changes in mean NHP scores in different dimensions are computed after
      pain resolution to determine whether NHP scores provide more sensitive indicators
      of disease resolution. Third, linear regression is used to determine whether the
      impacts of disease on quality of life are measured adequately by the clinical
      parameters. These analyses show that use of the physical mobility and energy
      dimensions of the NHP increases understanding of disease prognosis; demonstrates
      the continuing impact of zoster on patients' sleep patterns and energy levels,
      disease symptoms not included as clinical measures, that persist after the
      cessation of zoster-associated pain; and gives a measure of the impact of zoster
      on the patient, which includes unmeasured and measured levels of severity.

PMID- 7723449
TI  - Clinical practice and patients' health status: how are the two related?
AB  - Now that we have the ability to measure patients' health outcomes, physicians and
      health care systems need to know how to manage these outcomes. What are the
      causal pathways that link clinical and health status concepts? What are the key
      points at which physicians and health care systems can intervene in effective and
      cost-effective ways? We have argued that the elegant biomedical model that
      physicians use to understand disease is a blunt tool in the dissection of illness
      and that valid, reliable, and richly descriptive measures of HRQL fail at
      clinical tasks because causal linkages between clinical processes and health
      status outcomes have not yet been made convincingly, at either the conceptual or
      the empiric level. One approach to this problem is to develop and test causal
      models that explore the relationships among different measures of health status
      in an attempt to elucidate the "genesis" and "pathogenesis" of disorders of HRQL.
      Once physicians and health care systems know more about the determinants of poor
      health status and the mechanisms by which it occurs, creative attempts to
      intervene at multiple points in a causal pathway may be possible, making outcomes
      management a more realistic goal.

PMID- 7723450
TI  - Use of outcomes studies by a managed care organization: valuing measured
      treatment effects. Aetna Health Plans.

PMID- 7723451
TI  - Measuring the success of treatment in patient terms.
AB  - Measuring the success of major surgeries such as total hip and total knee
      replacement is important for both case selection and public policy. Patients,
      purchasers, and practitioners must choose among clinical scoring systems, health
      status measures, and patient satisfaction ratings to monitor performance and
      ensure appropriate use of costly procedures. The present study compares results
      from the Medical Outcomes Study Short Form 36 (SF-36) Health Status Survey and
      clinical scoring systems to direct patient ratings of success. Data come from a
      study of 128 total knee-replacement procedure and 211 total hip replacements.
      Analyses indicate that for both hip and knee patients, success is related closely
      to posttreatment physical function and bodily pain. Patient ratings of success
      also are related to the clinical scores used by physicians. Success is related
      less to change from pretreatment function for knee patients than for hip
      patients. Although patient ratings of success are generally consistent with other
      outcome measures, their relationship to patient expectations, satisfaction, and
      attributions need to be understood before they can become a useful tool for
      performance monitoring and case selection.

PMID- 7723452
TI  - The proximal-distal continuum of multiple health outcome measures: the case of
      cataract surgery.
AB  - This paper presents the concept of a proximal-distal continuum in health outcome
      measures. It indicates how this continuum can be used in the selection of outcome
      measures in health technology evaluation studies. Finally, it demonstrates
      several ways in which the placement of a specific health outcome measure in the
      proximal-distal continuum determines the overall statistical model of treatment
      and nontreatment variables. We identify five principles that relate to the above
      issues. The first three principles state that a larger effect of treatment on
      health outcomes will be seen when the following occur: 1) more proximal (e.g.,
      signs and symptoms, disease-specific outcomes) measures are examined, 2) the
      initial illness is more severe; and 3) pretreatment distal (e.g., role
      functioning, life satisfaction) outcome measures show relatively high impairment.
      Principle four indicates that distal outcomes are influenced more heavily by
      external (i.e., nontreatment) factors. Principle five states that a causal chain
      links each outcome measure in the continuum to the next more distal outcome
      measure. This last principle enables the determination of indirect relationships
      between treatment and outcomes. These principles are illustrated with data from a
      study on the effects of cataract surgery with intraocular lens implantation on
      patient outcome variables across the proximal-distal continuum.

PMID- 7723453
TI  - Comparing the quality-adjusted life-year output of two treatment arms in a
      randomized trial.
AB  - The quality-adjusted life year (QALY) is an outcome measure with two dimensions:
      wellness and time. It is difficult to compare the QALY output of two groups when
      subjects are observed for varying time periods, because both elements of the two
      dimensional outcome measure vary in all subjects. This paper evaluates the
      strengths and weaknesses of five approaches for making these comparisons. These
      approaches are: a subject-based approach, the elimination of time, calculation of
      the mean of available data, use of quality-adjusted survival analysis, and
      calculation of a maximum likelihood estimation. It is concluded that the maximum
      likelihood estimation offers significant advantages over the other methods.

PMID- 7723454
TI  - The effect of past and present illness experience on the valuations of health
      states.
AB  - The effects of age, sex, income, and other socioeconomic factors on valuations
      for health states have been reported in the literature. However, little attention
      has been paid to the influence of illness experience, either current or past, on
      valuations for of states. This paper addresses that question using six separate
      data sets covering some 1,900 subjects. Each data set contains information on
      self-reported current health status and experience of serious illness in self,
      family, and others. Past experience of illness has not been found to affect
      valuations, but there is some evidence to suggest that, compared with those who
      claim to be in full health, those who describe their current health as
      dysfunctional give higher valuations (i.e., closer to good health) for all health
      states, and particularly so for the more severe states. The most striking result,
      however, concerns the relationship between respondents' valuations of their own
      health and their subsequent valuations of hypothetical health states. In all
      studies, it has been observed that a low self-rated health status is associated
      with significantly lower valuations of less severe states, including full health.
      The findings of this paper suggest a real dilemma for health services researchers
      and policy makers. The importance of the choice of valuations used in the
      evaluation of health care now must be recognized, because different results may
      be obtained according to the current health status of those respondents from whom
      valuations are.

PMID- 7723455
TI  - Comparison of methods for the scoring and statistical analysis of SF-36 health
      profile and summary measures: summary of results from the Medical Outcomes Study.
AB  - Physical component summary (PCS) and mental component summary (MCS) measures make
      it possible to reduce the number of statistical comparisons and thereby the role
      of chance in testing hypotheses about health outcomes. To test their usefulness
      relative to a profile of eight scores, results were compared across 16 tests
      involving patients (N = 1,440) participating in the Medical Outcomes Study.
      Comparisons were made between groups known to differ at a point in time or to
      change over time in terms of age, diagnosis, severity of disease, comorbid
      conditions, acute symptoms, self-reported changes in health, and recovery from
      clinical depression. The relative validity (RV) of each measure was estimated by
      a comparison of statistical results with those for the best scales in the same
      tests. Differences in RV among scales from the Medical Outcomes Study 36-Item
      Short-Form Health Survey (SF-36) were consistent with those in previous studies.
      One or both of the summary measures were significant for 14 of 15 differences
      detected in multivariate analyses of profiles and detected differences missed by
      the profile in one test. Relative validity coefficients ranged from .20 to .94
      (median, .79) for PCS in tests involving physical criteria and from .93 to 1.45
      (median, 1.02) for MCS in tests involving mental criteria. The MCS was superior
      to the best SF-36 scale in three of four tests involving mental health. Results
      suggest that the two summary measures may be useful in most studies and that
      their empiric validity, relative to the best SF-36 scale, will depend on the
      application. Surveys offering the option of analyzing both a profile and
      psychometrically based summary measures have an advantage over those that do not.

PMID- 7723456
TI  - The significance of treatment effects: significance to whom?

PMID- 7723457
TI  - The significance of treatment effects: the clinical perspective.

PMID- 7723458
TI  - Assessing the significance of treatment effects: comments from the perspective of
      ethics.
AB  - The process of designing research protocols for testing treatment effects and
      reporting the results of such research demands both explicit and implicit value
      judgments. When measuring the effects of alternative treatments, those judgments
      can include decisions about what outcomes to measure and for which persons they
      should be measured, how to aggregate disparate outcomes, and how to decide
      whether differences are substantial enough to differentiate between treatments.
      Researchers and reviewers often do not acknowledge problems of this sort, and
      default solutions are based on common usage rather than any epistemologic
      justification. Acknowledging the value commitments inherent in choices about
      research methods should serve to increase variation in methods rather than
      constrain them within conventional patterns. Especially with research intended to
      shape policy and practice, more thoughtful choices, humility in recognizing the
      limits of available methods, and flexibility in establishing the thresholds for
      significant differences for each study seem to be justified. The choices
      researchers make should be documented and the reasons for those choices should be
      given explicitly in publications and presentations so that readers and other
      users of the information are enabled and expected to bear more responsibility for
      interpreting and applying the findings appropriately.

PMID- 7723459
TI  - Public policy and the application of outcomes assessments: paradigms versus
      politics.

PMID- 7723460
TI  - Controlling for confounding by indication for treatment. Are administrative data
      equivalent to clinical data?
AB  - There has been controversy about whether confounding by indication for treatment-
      that is, owing to physicians' conscious efforts to base treatment decisions on
      patients' pretreatment prognoses--makes nonrandomized, observational comparisons
      of treatments invalid. Some now believe evidence from studies of practice
      variation means that physicians' treatment decisions have little relationship to
      patients' prognostic clinical characteristics. They therefore believe that
      patients who receive different treatments should vary little in their baseline
      prognoses, and multivariable statistical methods should easily be able to adjust
      for any resultant confounding, even when analyses are restricted to
      administrative rather than clinical data. The objective of this study is to
      determine whether adjusting for variables found in administrative data sets
      produces the same results as does adjusting for clinical variables. Data were
      reanalyzed from a previously enrolled prospective sequential cohort of 227
      hospitalized patients with suspected bacteremia who had blood cultures. The
      treatment under study was aminoglycoside therapy given empirically, that is,
      before blood culture results were known. The outcome of interest was death during
      hospitalization. Univariable analyses suggest that empiric aminoglycoside therapy
      had a positive association with mortality, by univarible logistic regression,
      odds ratio (OR = 3.1 (95% confidence interval = [1.6, 5.8]). Few administrative
      variables had univariable associations with aminoglycoside use or death.
      Multivariable analyses that controlled for them still suggest that
      aminoglycosides increased mortality; for example, in one model, adjusted OR = 3.2
      (1.6, 6.5). Many clinical variables were strongly associated with aminoglycoside
      use or death. Analyses that controlled for them suggested that empiric
      aminoglycosides did not increase mortality; for example, in one model, adjusted
      OR = 1.2 (0.55, 2.7.) Results of adjustment for confounding using administrative
      data disagreed with the results of adjustment using clinical data. It is
      concluded that nonrandomized, observational outcome studies that fail to control
      for prognostic differences between patients receiving different treatments may
      not always be valid.

PMID- 7723461
TI  - Development and testing of a new measure of case mix for use in office practice.
AB  - Case mix has been shown to be of critical importance in studies of effectiveness
      and quality of care using health outcomes. How these variables are defined,
      combined, and used to adjust or increase precision in tests for differences in
      health outcomes has been a source of controversy. Because existing measures were
      developed to adjust mortality and have marginal relevance for the adjustment of
      functional status outcomes, especially in ambulatory settings, the authors
      developed a measure of case (or patient) mix that is specifically designed to
      adjust functional status outcomes measured in office practice or out-of-hospital
      settings. This measure, developed as part of Type II Diabetes Patient Outcomes
      Research Team project, uses patients' reports of symptoms and conditions, as well
      as patients' ratings of symptom intensity to characterize total disease burden.
      It differs from other measures of case mix in lack of dependence on diagnoses.
      Separate measures were developed for each of 15 different disease categories
      (e.g., chronic lung disease) grouped by body system affected. Within each
      measure, questionnaire items were combined to rate the severity of that disease
      on a 1 to 4 scale, according to definitions provided by clinicians. A single,
      global measure was developed by aggregating the 15 measures, weighted according
      to the expected impact of each disease category on functional outcomes and
      disability. In a sample of 1,738 patients, significant relationships were
      observed between the global case mix measure and functional status, disability
      days, and service utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723462
TI  - Propensity score adjustment for pretreatment differences between hospitalized and
      ambulatory patients with community-acquired pneumonia. Pneumonia Patient Outcomes
      Research Team (PORT) Investigators.
AB  - A primary goal of the Pneumonia Patient Outcomes Research Team (PORT) multicenter
      cohort study is to identify a subgroup of patients with community-acquired
      pneumonia (CAP) who could be safely treated on an ambulatory basis. The medical
      outcomes of inpatients and outpatients are to be compared. Propensity score
      adjustment provides a unified way to control for pretreatment differences in the
      analysis of all the outcomes in this nonrandomized study by defining "comparable"
      patients as those with the same propensity score (i.e., the same probability of
      hospitalization). Data for 747 patients (35.5% hospitalized) with CAP in the
      Pneumonia PORT study illustrate the development and assessment of a propensity
      score adjustment. A classification tree algorithm defined seven propensity score
      strata with hospitalization probabilities ranging from 6.5% to 76.5%.
      Statistically significant pretreatment imbalances favoring the outpatients were
      found for 29 of 44 baseline variables considered; after stratification on the
      propensity score, only 13 of the 29 imbalances remained statistically significant
      at the 0.05 level. Post hoc stratification on the estimated propensity score
      consistently reduced, but did not completely eliminate, systematic baseline
      differences between ambulatory and hospitalized patients with CAP. Regression
      adjustment can be used in conjunction with propensity score stratification to
      adjust further for the remaining identified imbalances.

PMID- 7723463
TI  - Does recollection error threaten the validity of cross-sectional studies of
      effectiveness?
AB  - New cross-sectional studies have been designed to evaluate therapeutic
      effectiveness of medical and surgical treatments. The extent to which error in
      recollection may threaten the validity of conclusions reached in these studies
      has not been determined. The purpose of this research was to evaluate the impact
      of recollection error by comparing patients' prospectively acquired reports about
      their condition before total hip replacement with their recollections of their
      preoperative condition obtained several years after surgery. A total of 104
      patients prospectively completed the Hip Rating Questionnaire (HRQ), a valid,
      reproducible, responsive, disease-specific scale composed of four domains (pain,
      walking, function, and impact of hip arthritis on overall health). These same
      patients then completed the HRQ several years after surgery by recalling their
      preoperative condition. Current postoperative condition was also obtained several
      years after surgery with the HRQ. Patient characteristics include: 55% were
      women, mean age was 67 years, 90% had osteoarthritis, 78% had no prognostically
      significant comorbid disease, and the mean time interval between surgery and
      recall was 2.5 years. Comparison of prospective and recalled responses with the
      weighted kappa and intraclass correlation coefficients showed poor to fair
      agreement in three domains, and moderate agreement in the fourth domain. Overall,
      the directions of the recollection errors were toward patients' recalling more
      pain, better walking, better function, and worse impact of hip arthritis on
      health than they reported before surgery. When the data were stratified to
      determine if there were systematic biases among major patient subgroups, there
      were discrepancies in the percentage of patients within each subgroup who had
      recollection error for the different domains, as well as differences in the
      magnitudes and directions of the recollection errors. These results indicate that
      relying on patients' recollections does not provide an accurate measure of
      preoperative state, and that attempting to adjust data is not feasible because
      the directions and magnitudes of recollection error vary for major subgroups of
      patients. In addition, when outcome was assessed using postoperative HRQ
      responses, the cross-sectional data overestimated the effectiveness of total hip
      replacement in 68% of patients. It is concluded that cross-sectional data do not
      accurately portray baseline preintervention condition and therefore can lead to
      overestimating, as in this instance, or to underestimating effectiveness.

PMID- 7723464
TI  - Measuring effects without randomized trials? Options, problems, challenges.
AB  - The idea of using information routinely generated in the course of health care
      delivery for assessing the relative efficacy of alternative therapies has an
      undeniable attraction. If feasible, it would enable the difficulties of running a
      randomized controlled trial (RCT) to be bypassed. But grave obstacles, both
      practical and theoretical, beset the effort. If, nonetheless, the data base
      approach is chosen, certain suggestions may be helpful. First, make sure that
      necessity actually prevents using an RCT. Reconsider that question. Special
      attention is due to two variants of the usual RCT: the "firms" approach and the
      large simple trial. If, after reconsideration, a data base approach still is
      chosen, then let the undertaking be carefully planned, with participation from
      those who will produce the data and also from future users of the results. Let
      the planning result in a protocol, and in provisions for a quality assurance
      program. Finally, it is time to respond to a challenge left us by David Byar:
      arrange to record why the patient is being given the therapy selected. This
      information should be a powerful adjustment variable; arranging to collect it
      will call for imaginative thinking, experimentation, and patience, but it is an
      idea deserving much effort.

PMID- 7723465
TI  - Reporting current, past, and changed health status. What we know about
      distortion.

PMID- 7723466
TI  - Measuring effectiveness. What to expect without a randomized control group.
AB  - Randomized controlled trials or studies are often considered the ideal way to
      evaluate the effectiveness of a treatment compared to a control. In such a study,
      the randomization procedure ensures that the subjects receiving the treatment and
      control are equal with respect to all conditions except for receiving the
      treatment or the control. Differences found by statistical comparisons of the
      results of such a study can be attributed to the effect of the treatment or how
      much the treatment differs from the control when all other things are held
      constant. Randomized controlled trials are not always possible, and even when
      possible they are often performed with such restrictions that they do not provide
      the true measure of the effectiveness of the treatment in the "real world" or
      under "conditions of usual practice." This article reviews the use of
      nonrandomized studies to measure effectiveness when a randomized control group is
      not available. Various types of nonrandomized studies are reviewed, along with
      their advantages and disadvantages. Often, these studies require statistical
      adjustments such as matching or covariance analysis to adjust for inequalities or
      to remove biases between the treatment and control groups; these are reviewed as
      well.

PMID- 7723467
TI  - Specific neurotropic effects of dihydropyridine calcium channel blockers.

PMID- 7723468
TI  - Comparison of the effects of dopamine1- and dopamine2-receptor agonists on the
      cAMP generating system in canine coronary and renal arteries.
AB  - To further evaluate the functional significance of dopamine (DA) receptors in
      different vasculature, in this study we compared the effects of D1- and D2
      receptor agonists on canine coronary and renal arteries by measuring adenylate
      cyclase (AC) activity as a biomedical index of DA receptor function. It was found
      that both the selective D1-receptor agonist, fenoldopam, and the D2-receptor
      agonist, propyl-butyl-dopamine (PBDA), induced a dose-related increases in cAMP
      formation in coronary and renal arteries; however, the magnitude of increase in
      the renal artery was remarkably greater than that in the coronary artery. The
      stimulatory effect on AC activity of fenoldopam was significantly more potent
      than that of PBDA. The selective D1-receptor antagonist, SCH23390, blocked
      fenoldopam- and PBDA-induced cAMP production, while the selective D2-receptor
      antagonist, domperidone, was without effect on the increase of cAMP elicited by
      PBDA. After beta-adrenergic blockade with propranolol, fenoldopam still increased
      the cAMP level significantly but to a much lesser degree. The existence of
      postsynaptic D2-receptor associated with inhibition of cAMP formation could not
      be demonstrated in this study. These data suggest the presence of D1-receptors
      associated with stimulation of AC activity in both renal and coronary arteries.
      However, there are much fewer receptor sites in the coronary artery than in the
      renal artery, suggesting less physiological importance of such receptors in the
      coronary artery than in the renal artery.

PMID- 7723469
TI  - Indirect talk of signalling systems in endotoxicosis: cross-talk alternatives.
AB  - This work evaluated indirect talk, a system of communication between two
      secondary messengers which uses a third modulating messenger/compound for
      communication. It expands on our previous report (6) of mean levels and
      univariate linear/non-linear relationships. It presents results using
      multivariate testing with vectorial modeling. The signal transduction systems
      (sts) studied through 125I-radioimmunoassay involved: adenosine 3':5' -cyclic
      monophosphate (cAMP); and the guanylate cyclase sts via guanine 3':5' -cyclic
      monophosphate (cGMP). Through multivariate testing, the dependency of a specified
      parameter was determined relative to two or more independent parameters. The
      contributing aspects of each of the independent variables were assigned to either
      2- or 3-dimensional axes. Through the vector analyses the topic of indirect talk
      was well aspected. Multivariate equations showed that communication between two
      systems occurred. Vectorial analysis showed that the direct/indirect mechanism of
      that communication (namely, indirect talk) occurred. Such analysis leads to a
      greater understanding of endotoxemia that adversely affects skeletal muscle.

PMID- 7723470
TI  - Effects of a non-xanthine adenosine antagonist, CGS 15943, and a
      phosphodiesterase inhibitor, Ro 20-1724, in a light/dark test in mice.
AB  - We investigated the effects of a non-xanthine adenosine receptor antagonist, CGS
      15943, and a non-xanthine phosphodiesterase inhibitor, Ro 20-1724, in a
      light/dark test in mice. CGS 15943 at a dose of 50 mg/kg had no significant
      effects on any parameter, although at 10 mg/kg it significantly antagonized
      decreases in locomotion and rearing behavior induced by treatment with A1 and A2
      selective agonists, N6-cyclopentyladenosine and CGS 21680 respectively. On the
      other hand, Ro 20-1724 decreased locomotion and rearing behavior in the light and
      dark zones, number of shuttle crosses between both zones, and the time spent in
      the light zone dose-dependently at doses ranging from 1-10 mg/kg. In conclusion,
      the phosphodiesterase inhibitor decreased all parameters in the light/dark test,
      while the adenosine antagonist showed no effect.

PMID- 7723471
TI  - Effect of polysaccharide peptide (PSP) on glutathione and protection against
      paracetamol-induced hepatotoxicity in the rat.
AB  - The protective effects of polysaccharide peptide (PSP), isolated from Coriolus
      versicolor COV-1, on paracetamol-induced hepatotoxicity was investigated in this
      study. The effect of PSP on hepatic glutathione status was also studied. PSP (300
      mg/kg, i.p.) caused a 40% depletion of hepatic reduced glutathione (GSH) with a
      concomitant 50% increase in oxidized glutathione (GSSG), thus producing a 3-fold
      increase in the GSSG/GSH ratio. The PSP-induced GSH depletion itself had no
      hepatotoxic effects. PSP protected against paracetamol-induced hepatotoxicity by
      decreasing the paracetamol-induced elevation of serum glutamic-pyruvic
      transaminase (SGPT) activity from 511 +/- 71 U/ml to 187 +/- 58 U/ml (controls
      without paracetamol 105 +/- 4 U/ml) and serum glutamic-oxaloacetic transaminase
      (SGOT) activity from 462 +/- 63 to 152 +/- 48 U/ml (controls without paracetamol
      54 +/- 6 U/ml). PSP did not reverse the depletion of total glutathione (GSH+GSSG)
      by the toxic dose of paracetamol. The GSSG/GSH ratio, which is a measure of
      oxidative stress, was significantly (p < 0.05) decreased when PSP was
      coadministered with paracetamol. PSP dose-dependently decreased the covalent
      binding of [14C]-paracetamol to microsomal proteins in vitro. When PSP was given
      to rats subchronically for 7 days (300 mg/kg/day, i.p.), the subsequent
      microsomes obtained also showed a 25% decrease in covalent binding to [14C]
      paracetamol, suggesting that PSP interacted with the microsomal proteins rather
      than the chemically reactive metabolite of paracetamol. The changes in the
      binding affinity and capacity of the microsomal proteins by PSP may be related to
      its ability to alter the redox potential as indicated by the effects of PSP on
      the GSSG/GSH status.

PMID- 7723472
TI  - Caffeine-induced increase of adenosine deaminase activity in mammalian lymphoid
      organs.
AB  - Adenosine deaminase (ADA) activity was increased in spleen and thymus of rat with
      single and multiple caffeine treatments (10 and 20 mg/kg/day). The stimulation
      was greater at the higher dose. ADA activity of liver was not affected under
      these conditions. This study indicates that caffeine may potentiate immunity with
      the modulation of adenosinergic system through increasing splenic and thymic ADA
      activity.

PMID- 7723473
TI  - Kindling model of epilepsy.

PMID- 7723474
TI  - [Three years with Adel--some experiences. Shortages in medical care quality at
      certain nursing homes].

PMID- 7723475
TI  - [Catch 22 in research may be eliminated by registration].

PMID- 7723476
TI  - [Do not remove physicians' names from drug packages].

PMID- 7723477
TI  - [How is a physician being cleared from accusations?].

PMID- 7723478
TI  - [Education of junior physicians deserves first priority].

PMID- 7723479
TI  - [A new mysterious disease group. Autoimmune sensorineural hearing loss].

PMID- 7723480
TI  - [Hirschsprung disease. A receptor defect].

PMID- 7723482
TI  - [PCR in the diagnosis of tuberculosis. A rapid, sensitive and specific
      technique].

PMID- 7723481
TI  - [Diagnosis of distal urinary disorders. Routine determination of resistance of
      low-count bacteria in urinary specimens is not justified].

PMID- 7723483
TI  - [Acute intermittent porphyria. Risk of secondary hypertension--needs follow-up!].

PMID- 7723484
TI  - [Experiences from the amalgam unit at Huddinge hospital. No mercury poisoning was
      diagnosed].

PMID- 7723485
TI  - [Ovarian cancer. New therapeutic techniques and new drugs give the patients
      hope].

PMID- 7723486
TI  - [Ergotamine poisoning in unclear ischemia. Do not overlook unusual effects in
      "acute abdomen"!].

PMID- 7723487
TI  - [How to tell bad news?].

PMID- 7723488
TI  - [Telephone information about malignant melanoma is common. More patients receive
      information about their diagnosis at their second visit].

PMID- 7723489
TI  - [A devastating epidemic on its way to a global outbreak. Women and children are
      most susceptible].

PMID- 7723490
TI  - [Vibrations as the cause of low back pain disorders. Professional drivers are at
      risk].

PMID- 7723491
TI  - [Rapid development within interventional radiology. Special training in new
      radiologic methods is needed].

PMID- 7723492
TI  - [Correct diagnosis means correct compensation. The DRG system needs internal
      control].

PMID- 7723493
TI  - Hepatitis B vaccine boosting: the debate continues.

PMID- 7723494
TI  - Laser tackles bone.

PMID- 7723495
TI  - Physician shortages in rural America.

PMID- 7723496
TI  - Placebo-controlled trial of safety and efficacy of intraoperative controlled
      delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The
      Polymer-brain Tumor Treatment Group.
AB  - Chemotherapy for brain tumours has been limited because of difficulty in
      achieving adequate exposure to the tumour without systemic toxicity. We have
      developed a method for local sustained release of chemotherapeutic agents by
      their incorporation into biodegradable polymers. Implantation of the drug
      impregnated polymer at the tumour site allows prolonged local exposure with
      minimal systemic exposure. We conducted a randomised, placebo-controlled,
      prospective study to evaluate the effectiveness of biodegradable polymers
      impregnated with carmustine to treat recurrent malignant gliomas. In 27 medical
      centres, 222 patients with recurrent malignant brain tumours requiring re
      operation were randomly assigned to receive surgically implanted biodegradable
      polymer discs with or without 3.85% carmustine. Randomisation balanced the
      treatment groups for all of the prognostic factors examined. Median survival of
      the 110 patients who received carmustine polymers was 31 weeks compared with 23
      weeks for the 112 patients who received only placebo polymers (hazard ratio =
      0.67, p = 0.006, after accounting for the effects of prognostic factors). Among
      patients with glioblastoma, 6-month survival in those treated with carmustine
      polymer discs was 50% greater than in those treated with placebo (mortality = 32
      of 72 [44%] vs 47 of 73 [64%], p = 0.02). There were no clinically important
      adverse reactions related to the carmustine polymer, either in the brain or
      systemically. Interstitial chemotherapy delivered with polymers directly to brain
      tumours at the time of surgery seems to be a safe and effective treatment for
      recurrent malignant gliomas.

PMID- 7723497
TI  - Insertion/deletion polymorphism in the angiotensin-converting enzyme gene and
      risk of restenosis after coronary angioplasty.
AB  - Early restenosis in over 30% of cases limits the benefits of percutaneous
      transluminal coronary angioplasty (PTCA). The mechanisms that underlie restenosis
      are uncertain, although experimental evidence suggests that the renin-angiotensin
      system is involved in the vascular response to angioplasty. An
      insertion(I)/deletion(D) polymorphism in the angiotensin-converting enzyme (ACE)
      gene, which influences plasma ACE level, has been associated with an increased
      risk of myocardial infarction in those with the DD genotype. To investigate
      whether this polymorphism influences the risk of restenosis after PTCA, 233
      patients who underwent single-vessel angioplasty in the Subcutaneous Heparin and
      Angioplasty Restenosis Prevention (SHARP) study were genotyped for the I/D
      polymorphism and pre-PTCA, post-PTCA, and 4-month clinical and quantitative
      angiographic data were compared in the three genotype groups. The groups, (II 53,
      ID 117, and DD 63) were well matched for baseline clinical and both pre- and post
      PTCA angiographic features. At 4-month follow-up there was no significant
      difference between the genotype groups with respect to any of the quantitative
      angiographic criteria of restenosis: minimal luminal diameter at the site of the
      angioplasty (DD 1.35 [SE 0.10] mm, ID/II 1.43 [0.05] mm, difference -0.08 [95% CI
      -0.30 to 0.14]), numbers of subjects with more than 50% diameter stenosis (DD
      49%, ID/II 46%, relative risk 1.06 [0.79 to 1.43]), or the number of subjects
      with more than 50% loss of the acute diameter gain after PTCA (DD 54%, ID/II 43%,
      1.26 [0.94 to 1.67]). Likewise, there was no difference in the number of subjects
      with angina or a positive exercise stress test. We conclude that, in patients
      undergoing elective PTCA, the I/D polymorphism in the ACE gene does not influence
      the extent of restenosis, and typing for the polymorphism will not be a useful
      predictor of risk before the procedure.

PMID- 7723498
TI  - Transfer of myeloma idiotype-specific immunity from an actively immunised marrow
      donor.
AB  - The idiotype of myeloma immunoglobulin can be used as a unique tumour-specific
      antigen. We tested the hypothesis that tumour antigen-specific immunity can be
      transferred from bone-marrow-transplant donor to recipient. We immunised a
      healthy sibling donor with myeloma immunoglobulin from the plasma of the
      recipient, conjugated to an immunogenic carrier protein and emulsified in an
      adjuvant, before marrow transplantation. Detection of a lymphoproliferative
      response, a parallel response in the carrier protein, recovery of a recipient
      CD4+ T-cell line with unique specificity for myeloma idiotype, and demonstration
      by in-situ hybridisation that the cell line was of donor origin, proved that a
      myeloma idiotype-specific T-cell response was successfully transferred to the
      recipient. Donor immunisation with myeloma idiotype may represent a new strategy
      for enhancing the specific anti-tumour effect of allogeneic marrow grafts.

PMID- 7723499
TI  - CRIB (clinical risk index for babies), mortality, and impairment after neonatal
      intensive care. Scottish Neonatal Consultants' Collaborative Study Group and the
      International Neonatal Network.
AB  - Risk-adjustment may overcome the disadvantages of birthweight-specific
      comparisons of neonatal units. Risk-adjusted rates of death or impairment after
      18 months were compared in five tertiary and three non-tertiary neonatal units
      for 695 high-risk infants. CRIB (clinical risk index for babies) was more closely
      related than birthweight to death or impairment. After adjustment for risk with
      CRIB, deaths remained more likely after non-tertiary than tertiary care (odds
      ratio 1.90, 95% CI 1.1-3.3) but rates of impairment in survivors were nearly
      identical (0.97, 0.5-2.1). To improve performance further, risk-adjusted rates of
      death and impairment should be monitored for all neonatal units.

PMID- 7723500
TI  - Gastroschisis and reduced fetal heart-rate variability.
AB  - Most liveborn babies with gastroschisis do well after surgical repair, although
      about one-eighth of affected cases die late in utero. Our practice is to use
      weekly computerised cardiotocograph (CTG) analysis after week 34 of gestation in
      cases of gastroschisis. In a look-back at the records in 18 such singleton
      pregnancies, CTG showed 7 to be highly abnormal or preterminal. All but 1 of
      these 7 had a normal fetal heart rate. In all 7 cases, delivery was expedited.
      Only 1 infant had neurological sequelae, and in all the abdominal defect was
      successfully repaired. Monitoring of these high-risk pregnancies with serial
      computerised CTG may be helpful in timing delivery.

PMID- 7723501
TI  - Vertical transmission of hepatitis E virus.
AB  - Little is known about vertical transmission of hepatitis E virus from infected
      mothers to their infants. We studied eight babies born to mothers infected with
      hepatitis E in third trimester. One baby was icteric at birth with elevated
      transaminases and four babies had anicteric hepatitis. Two babies were born with
      hypothermia and hypoglycaemia and died within 24 h; one had massive hepatic
      necrosis. Hepatitis E virus RNA was detected by PCR in cord or birth blood
      samples of five infants. Six infants had evidence of hepatitis E infection. We
      conclude that hepatitis E virus is commonly transmitted from infected mothers to
      their babies with significant perinatal morbidity and mortality.

PMID- 7723502
TI  - Clinical applications of ribozymes.

PMID- 7723503
TI  - After the Republicans' first 100 days.

PMID- 7723504
TI  - Kaposi's sarcoma and new herpesvirus.

PMID- 7723505
TI  - Kaposi's-sarcoma-associated herpesvirus in HIV-negative Kaposi's sarcoma.

PMID- 7723506
TI  - Cot mattresses and sudden infant death syndrome.

PMID- 7723507
TI  - Cot mattresses and sudden infant death syndrome.

PMID- 7723508
TI  - Cot mattresses and sudden infant death syndrome.

PMID- 7723509
TI  - Origin of male mediastinal germ-cell tumours.

PMID- 7723510
TI  - Zinc and duration of treatment of severe malnutrition.

PMID- 7723511
TI  - Posture, blood flow, and prophylaxis of venous thromboembolism.

PMID- 7723512
TI  - Posture, blood flow, and prophylaxis of venous thromboembolism.

PMID- 7723513
TI  - Fatal neonatal tracheal obstruction after expectant management of prolonged
      premature rupture of membrane.

PMID- 7723514
TI  - Accidental hypothermia.

PMID- 7723515
TI  - Malaria prophylaxis dosage.

PMID- 7723516
TI  - Prenatal diagnosis of spinal muscular atrophy by gene deletion analysis.

PMID- 7723517
TI  - Public health advocacy.

PMID- 7723518
TI  - Public health advocacy.

PMID- 7723519
TI  - A suitable case for treatment.

PMID- 7723520
TI  - Ethics committees.

PMID- 7723521
TI  - Ethics committees.

PMID- 7723522
TI  - HIV-1 subtype C in China.

PMID- 7723523
TI  - Transmission of oral Candida albicans strains between HIV-positive patients.

PMID- 7723524
TI  - Trial of streptokinase in ischaemic stroke.

PMID- 7723525
TI  - Smoking, Alzheimer's disease, and confounding with genes.

PMID- 7723526
TI  - Impaired olfactory function in Parkinson's disease.

PMID- 7723527
TI  - Selective MAOIs.

PMID- 7723528
TI  - Prostaglandin E2 and aspirin-induced asthma.

PMID- 7723529
TI  - Insecticide-treated bed nets in control of malaria in Africa.

PMID- 7723530
TI  - Treatment of pyoderma gangrenosum with colchicine.

PMID- 7723531
TI  - AIDS in Manchester, 1959?

PMID- 7723532
TI  - Nicotine for pyoderma gangrenosum.

PMID- 7723533
TI  - HCV-associated liver cancer.

PMID- 7723534
TI  - Ocular safety of antiulcer drugs.

PMID- 7723535
TI  - Body language in the emergency room.

PMID- 7723536
TI  - Cerebellitis associated with Lyme disease.

PMID- 7723537
TI  - Who owns medical technology?

PMID- 7723538
TI  - Colorectal adenomas on follow-up colonoscopy: is the cancer risk unchanged?

PMID- 7723539
TI  - Publishing economically.

PMID- 7723540
TI  - Cryptosporidium and the food supply.

PMID- 7723541
TI  - Advances in epidural analgesia for labour: progress versus prudence.

PMID- 7723542
TI  - Dopamine, dystonia, and the deficient co-factor.

PMID- 7723543
TI  - A randomised trial of compassionate care for the homeless in an emergency
      department.
AB  - Homeless adults often visit emergency departments and often leave dissatisfied.
      We tested whether compassionate care, by improving patient satisfaction, can
      alter subsequent use of emergency services. We identified 133 consecutive
      homeless adults visiting one inner-city emergency department who were not acutely
      psychotic, extremely intoxicated, unable to speak English, or medically unstable.
      Half were randomly assigned to receive compassionate contact from trained
      volunteers. All patients otherwise had usual care and were followed for repeat
      visits to emergency departments. We found that rates of use were high, with
      patients making an average of seven visits a year (0.60 per month). More than a
      third of all patients made two or more visits within two days of each other. The
      average number of visits per month after intervention was significantly lower for
      patients who received compassionate care (0.43 vs 0.65, p = 0.018). Analyses
      adjusting for each patient's previous rate of use confirmed that compassionate
      care led to a one third reduction in the number of return visits within one month
      (95% CI 14 to 40%). Compassionate management of selected homeless adults
      decreases repeat visits to the emergency department. One explanation is that
      patients tend to return frequently until they are satisfied with their treatment.

PMID- 7723544
TI  - Neuropsychological effects of long-term exposure to organophosphates in sheep
      dip.
AB  - Organophosphate-based pesticides are widely used throughout the world. The acute
      effects of over-exposure to such compounds are well known. Concern has also been
      expressed that long-term exposure may result in damage to the nervous system. In
      a cross-sectional study, we compared neuropsychological performance in 146 sheep
      farmers who were exposed to organophosphates in the course of sheep dipping with
      143 non-exposed quarry workers (controls). The farmers performed significantly
      worse than controls in tests to assess sustained attention and speed of
      information processing. These effects remained after adjustment for covariates.
      The farmers also showed greater vulnerability to psychiatric disorder than did
      the controls as measured by the General Health Questionnaire. There were no
      observed effects on short-term memory and learning. Repeated exposure to
      organophosphate-based pesticides appears to be associated with subtle changes in
      the nervous system. Measures should be taken to reduce exposure to
      organophosphates as far as possible during agricultural operations.

PMID- 7723545
TI  - A cost-effectiveness study of a randomised trial of laparoscopy versus laparotomy
      for ectopic pregnancy.
AB  - We compared the cost-effectiveness of therapeutic laparoscopy and open laparotomy
      for treatment of laparoscopically diagnosed ectopic pregnancy. Clinical outcomes
      of ectopic pregnancy treatment were based on results of a randomised trial done
      between 1987 and 1989 at Sahlgrenska University Hospital (Goteborg, Sweden). We
      estimated costs for inpatient and follow-up care of ectopic pregnancy by the two
      methods. Observed resource use (eg, procedure duration) was multiplied by 1992
      estimates of resource unit cost (eg, cost per minute of laparoscopy time), based
      on detailed internal cost accounting data from Huddinge University Hospital. By
      specified criteria, the initial procedure eliminated trophoblastic activity
      without major complications in 81% (95% CI: 68-90) of 52 laparoscopy patients,
      versus 95% (85-99) of 57 laparotomy patients. Residual trophoblast or
      complications were successfully treated in all remaining patients. Mean simulated
      costs (standard error) for the overall laparoscopy strategy were 28,058 (1780)
      Swedish kronor versus 32,699 (1080) kronor for laparotomy (p = 0.03). In the
      baseline simulation and most sensitivity analyses, laparoscopy produced final
      outcomes equivalent to those of laparotomy at lower costs. As laparoscopic
      outcomes improve, this newer approach should become increasingly preferable.

PMID- 7723546
TI  - Impairment of leukaemia-free survival by addition of interleukin-2-receptor
      antibody to standard graft-versus-host prophylaxis.
AB  - Graft-versus-host disease (GVHD) is the most important adverse effect of HLA
      matched allogeneic bone-marrow transplantation. T-cell depletion of the graft
      eliminates GVHD but also causes an unacceptable increase in rejections and
      leukaemic relapses. We have attempted to block the activation of resting T cells
      with a monoclonal antibody against the interleukin-2 receptor (33B3.1). 101
      patients with leukaemia (acute lymphocytic 22, acute myelogenous 34, chronic
      myeloid 45) in first complete remission or first chronic phase were randomly
      assigned to groups receiving standard post-transplantation immunosuppression
      (methotrexate plus cyclosporin; n = 50) or the standard treatment plus antibody
      33B3.1 (n = 51). There were 2 graft failures in the 33B3.1 group. The antibody
      did not significantly affect the cumulative frequency of acute GVHD of grade 2 or
      worse (19 [38%] vs 23 [46%]) but merely delayed its onset (median 36 [IQR 21-70]
      vs 25 [11-44] days; p < 0.01). At median follow-up of 58 (range 41-71) months,
      the antibody-treated group had significantly lower leukaemia-free survival (p <
      0.05) mainly because of a progressive increase in the rate of late relapses (p =
      0.08). Our findings confirm the importance of T cells in transplantation for
      leukaemia. The fine balance between the early modulation of transplant immunity
      and leukaemic control suggests that further anti-leukaemic measures may be needed
      when attempts are made to improve tolerance between the graft and the leukaemic
      host.

PMID- 7723547
TI  - Rapid antibody test for fragile X syndrome.
AB  - Fragile X syndrome is the most common known cause of inherited mental
      retardation. Identification of patients and carriers of fragile X syndrome is
      usually done with a DNA test system but we have developed a rapid antibody to
      identify fragile X patients. This non-invasive test requires only 1 or 2 drops of
      blood and can be used for screening large groups of mentally retarded people and
      neonates for fragile X syndrome.

PMID- 7723548
TI  - Emergence of fluoroquinolone-resistant tuberculosis in New York City.
AB  - 22 patients infected with fluoroquinolone-resistant Mycobacterium tuberculosis in
      New York City were identified between January, 1991, and November, 1993. In 16
      patients resistance arose as a result of inadequate or inappropriate treatment. 6
      patients had primary infection with fluoroquinolone-resistant organisms; 5
      acquired the organisms nosocomially. Seven distinct patterns of restriction
      fragment length polymorphism were identified in isolates from 21 patients.
      Fluoroquinolones should be restricted to patients with multidrug-resistant
      disease or intolerance to other antituberculosis drugs. All patients with
      multidrug-resistant tuberculosis should be on directly observed therapy.

PMID- 7723549
TI  - Examining the educated and the trained.

PMID- 7723551
TI  - European schools of public health in state of flux.
AB  - In 1992 there were in Europe 54 schools of public health and six out of eight
      possible structures were represented. To meet future needs two types (the US
      style school of public health as a stand-alone academic entity and the cross
      school programme in public health with formal ties to national public health
      authorities) seem to be the most promising alternatives. New schools should
      strive to take on one of these shapes, and the rejuvenation of existing schools
      might, via accreditation procedures, evolve in those directions too.

PMID- 7723550
TI  - Prognostic classification of breast ductal carcinoma-in-situ.
AB  - We present a new prognostic classification designated the Van Nuys classification
      for ductal carcinoma-in-situ (DCIS). The classification combines high nuclear
      grade and comedo-type necrosis to predict clinical recurrence. Three groups of
      DCIS patients were defined by the presence or absence of high nuclear grade and
      comedo-type necrosis: 1--non-high-grade DCIS without comedo-type necrosis, 2--non
      high-grade DCIS with comedo-type necrosis, 3--high-grade DCIS with or without
      comedo-type necrosis. There were 31 local recurrences in 238 patients after
      breast-conservation surgery 3.8% (3/80) in group 1, 11.1% (10/90) in group 2, and
      26.5% (18/68) in group 3. The 8-year actuarial disease-free survivals were 93%,
      84%, and 61%, respectively (all p < or = 0.05). The Van Nuys classification
      defines three distinct and easily recognisable groups, each of which has a
      different likelihood of local recurrence if treated with breast conservation.

PMID- 7723552
TI  - Misconduct in medical research.

PMID- 7723553
TI  - Puzzles of MD and PhD employment trends.

PMID- 7723554
TI  - Chernobyl nine years on.

PMID- 7723555
TI  - Antituberculous therapy and acute liver failure.

PMID- 7723556
TI  - Antituberculous therapy and acute liver failure.

PMID- 7723557
TI  - Antituberculous therapy and acute liver function.

PMID- 7723558
TI  - Antituberculous therapy and acute liver function.

PMID- 7723559
TI  - Clozapine therapeutic plunge in patient with Parkinson's disease.

PMID- 7723560
TI  - HCV and organ transplantation.

PMID- 7723561
TI  - Fatal cardiac tamponade after acupuncture through congenital sternal foramen.

PMID- 7723562
TI  - Supreme Court's decision on patients' rights in Japan.

PMID- 7723563
TI  - Who is a surgeon?

PMID- 7723565
TI  - Who is a surgeon?

PMID- 7723564
TI  - Who is a surgeon?

PMID- 7723566
TI  - Telemedicine in the Canary Islands.

PMID- 7723567
TI  - Drug-licensing anomalies and Parkinson's disease.

PMID- 7723568
TI  - Colchicine for secondary nephropathic amyloidosis in cystic fibrosis.

PMID- 7723569
TI  - Kaposi's sarcoma and new herpesvirus.

PMID- 7723570
TI  - Sex in adolescents.

PMID- 7723571
TI  - p53 protein overexpression and chemosensitivity in breast cancer.

PMID- 7723572
TI  - p53 protein overexpression and chemosensitivity in breast cancer. Institut
      Gustave-Roussy Breast Cancer Group.

PMID- 7723573
TI  - Ondansetron for intractable vertigo complicating acute brainstem disorders.

PMID- 7723574
TI  - Interval cancers in hereditary non-polyposis colorectal cancer (Lynch syndrome)

PMID- 7723575
TI  - Adjuvant intraportal chemotherapy for colorectal cancer.

PMID- 7723576
TI  - Leprosy.

PMID- 7723577
TI  - Vitamin D.

PMID- 7723578
TI  - Vitamin D.

PMID- 7723579
TI  - Microbial production of testosterone.

PMID- 7723580
TI  - Darkroom hepatitis after exposure to hydroquinone.

PMID- 7723581
TI  - Enhancing effect of DQ-2511 on gastric emptying of spontaneously hypertensive
      rats.
AB  - The present study was designed to clarify the potential of DQ-2511 (3-[[[2-(3,4
      dimethoxyphenyl)ethyl]carbamoyl]carbamoyl]methyl] amino-N-methylbenzamide:
      ecabapide) as a gastroprokinetic agent in spontaneously hypertensive rats (SHR).
      The gastric emptying of SHR was clearly retarded relative to that of weight
      matched normotensive Wistar-Kyoto (WKY) rats when evaluated by the acetaminophen
      (APAP) method with the semi-solid test meal. There was, however, no significant
      difference between both strains in gastric mucosal blood flow (GMBF) determined
      by means of a laser doppler flowmetry. A 2-week treatment of SHR with DQ-2511 (1
      mg/kg, oral) stimulated gastric emptying without affecting body weight gain or
      indirect systolic blood pressure (SBP), whereas cisapride (3 and 10 mg/kg, oral)
      had no effect under the same conditions. The pharmacological characteristics of
      DQ-2511 as a gastroprokinetic agent are discussed on the basis of these results.

PMID- 7723582
TI  - Central nervous system noradrenergic and dopaminergic turnover in response to
      acute neuroleptic challenge.
AB  - The objective of this study was to obtain direct neurochemical measures of the
      central nervous system's response to a typical neuroleptic, haloperidol, in human
      subjects. Nine healthy volunteers participated in this study. Central nervous
      system neuronal activity was assessed by measuring the plasma concentration and
      overflow from the brain of dopamine, norepinephrine, and their lipophilic and
      acidic metabolites after acute intravenous administration of haloperidol. By
      combining bilateral internal jugular vein blood sampling with cerebral blood flow
      scans we were able to differentiate between cortical and subcortical responses to
      haloperidol. The central nervous system response to haloperidol administration
      displayed a degree of regional specificity. Dopamine release, estimated from the
      overflow of homovanillic and dihydroxyphenylacetic acids, was reduced in cortical
      but not subcortical brain regions. Norepinephrine turnover was increased in
      cortical and subcortical brain regions. The overflow of homovanillic acid from
      the brain into the internal jugular veins was not related quantitatively to the
      arterial plasma concentrations of the catecholamines examined, homovanillic and
      dihydroxyphenylacetic acids or prolactin. Measurements of catecholamines and
      their metabolites in arterial plasma gave little indication as to monoaminergic
      neuronal activity in the brain.

PMID- 7723583
TI  - Conserved delta-activity in reverse enantiomeric opioid peptide.
AB  - A reverse enantiomeric peptide has a reversed amino acid sequence with
      enantiomeric amino acid residues compared with its parent peptide. In most cases
      the random change of amino acid sequence or chirality might be expected to bring
      about significant changes in peptide activity. However, the reverse enantiomeric
      peptides of Leu-enkephalin and Tyr-D-Ala-Gly-Phe-D-Leu (DADLE) have shown
      affinity for the opioid delta-receptor, but not for mu- or kappa-receptors. This
      suggests that delta-opioid receptor recognition occurs primarily through
      interaction with the peptide side chains, since the native opioid peptide and its
      reverse enantiomer are able to have similar side-chain conformation.

PMID- 7723584
TI  - Ameliorating effects of histidine on scopolamine-induced learning deficits using
      an elevated plus-maze test in mice.
AB  - We investigated the effects of histidine on scopolamine-induced learning deficits
      in the elevated plus-maze test in mice. In this test, transfer latency (TL), the
      time mice took to move from the open arm to the enclosed arm, was used as an
      index of learning and memory. Intraperitoneal administration of scopolamine (0.5
      mg/kg) prolonged the TL on day 2 compared with that in the saline-treated group.
      Histidine loading (500, 800 and 1600 mg/kg) reversed the prolongation of the TL
      induced by scopolamine. This ameliorating effect of histidine was abolished by
      alpha-fluoromethylhistidine, an inhibitor of histidine decarboxylase, suggesting
      that histidine itself has no such ameliorating effect. Moreover, the ameliorating
      effect of histidine was antagonized by a histamine H1 receptor antagonist,
      pyrilamine. However, zolantidine, a histamine H2 receptor antagonist, showed no
      antagonism of the effect of histidine. Thus, histamine, a decarboxylated product
      of histidine, elicited an ameliorating effect on scopolamine-induced learning
      deficit via histamine H1 receptors in mice. These findings clearly indicated that
      there is a close relationship between histaminergic and cholinergic systems in
      the brain, and that histamine may play certain important roles in learning and
      memory.

PMID- 7723585
TI  - Anticonvulsant activity of caramiphen analogs.
AB  - Caramiphen potently blocks maximal electroshock (MES)-induced seizures in mice
      and rats. The anticonvulsant mechanism has been hypothesized to be due to high
      affinity binding to sigma recognition sites in brain. To study the structure
      activity relationship for anticonvulsant activity of caramiphen we evaluated 8
      analogs in MES-induced seizures in rats and also determined whether a correlation
      exists between anticonvulsant potency and sigma binding affinity. Some of the
      analogs potently inhibited sigma binding but were devoid of anticonvulsant
      activity. Aminocaramiphen 2 (ED50 = 3.4 mg/kg) and N-methyl-4-piperidinyl 1
      phenylcyclopentanecarboxylate 9 (ED50 = 4.8 mg/kg) showed anticonvulsant activity
      comparable to caramiphen (ED50 = 3.1 mg/kg), although in sigma binding assays the
      affinities were 3-and 30-fold less than caramiphen, respectively. In the presence
      of 250 microM of phenytoin, caramiphen and p-aminocaramiphen showed 3- to 5-fold
      increases in affinity for [3H](+)pentazocine binding, whereas piodocaramiphen,
      which was inactive as an anticonvulsant, showed no change in affinity for sigma
      binding. These results indicate that anticonvulsant activity of the caramiphen
      analogs is not due to interaction with sigma binding sites.

PMID- 7723586
TI  - Ginsenosides of the protopanaxatriol group cause endothelium-dependent relaxation
      in the rat aorta.
AB  - The vasoactive effects of several ginsenosides, purified from Panax ginseng, were
      tested in the rat aorta. Ginsenosides from the protopanaxatriol group and its
      purified ginsenosides Rg1 and Re cause endothelium dependent relaxation which is
      associated with the formation of cyclic GMP. Both responses to these
      protopanaxatriol-containing ginsenosides are inhibited by methylene blue, an
      inhibitor of soluble guanylate cyclase and of nitric oxide synthase. In contrast,
      ginsenosides from the protopanaxadiol group and its purified ginsenosides Rb1 and
      Re do not affect vascular tone or production of cyclic GMP in the rat aorta.
      These findings demonstrate that ginsenosides from the protopanaxatriol group but
      not from the protopanaxadiol group enhance the release of nitric oxide from
      endothelial cells and may contribute to the beneficial effect of ginseng on the
      cardiovascular system.

PMID- 7723587
TI  - Linkage of reduction in 1-phosphatidylinositol 4-kinase activity and inositol
      1,4,5-trisphosphate concentration in human ovarian carcinoma cells treated with
      quercetin.
AB  - Quercetin inhibited 1-phosphatidylinositol (Pl) 4-kinase, EC 2.7.1.67 (Pl kinase)
      activity in a concentration-dependent manner (IC50 = 4 microM) in particulate
      extracts from human ovarian carcinoma. In OVCAR-5 cells quercetin produced growth
      inhibition (IC50 = 63 microM) and cytotoxicity (LC50 = 17 microM). The growth
      inhibition by quercetin was accompanied by an 80% decrease in Pl kinase activity
      and a 65% decrease in the concentration of the second messenger, inositol 1,4,5
      trisphosphate (IP3). When human OVCAR-5 cells were plated and expressed their
      neoplastic proliferative program in the log phase, Pl kinase and Pl 4-phosphate 5
      kinase, EC 2.7.1.68 (PIP kinase) activities coordinately increased to a peak of
      5.8- and 4.5-fold, respectively. The results demonstrate for the first time
      inhibition by quercetin of the enhanced capacity for operation of signal
      transduction in human ovarian carcinoma cells, thus providing a novel target in
      cancer cells.

PMID- 7723588
TI  - Antigen presentation is inhibited in vivo by betamethasone.
AB  - Aim of the present study was to assess whether betamethasone, a synthetic
      glucocorticoid used as immunosuppressant, could modify in vivo the antigen
      presentation by antigen presenting cells (APC). Interleukin-2 (IL-2) production
      by a T cell hybridoma specific for the hen egg white lysozyme (HEL) cultured in
      the presence of HEL and APC from treated or control mice was utilized as read
      out. Betamethasone induced a dose-dependent inhibition of antigen presentation.
      Fifty percent maximal response was observed with 1152 (95% confidence interval:
      948-1419) resident peritoneal macrophages from untreated animals, and 5843 (4700
      7445, 21, 235 (12,857-43,705), 28,313 (20,847-40,955) macrophages from mice
      injected for 3 days with betamethasone 10, 25, and 50 mg/kg respectively. Similar
      findings were obtained with spleen cells. When given for 3 days at 25 mg/kg,
      betamethasone reduced the number of cells recovered from the peritoneum by
      approximately half and from the spleen by one order of magnitude. One day vs. 3
      days treatment resulted in similar recovery of cells but lower inhibition of APC
      function. In the experimental conditions utilized, no carryover of betamethasone
      with APC could be demonstrated and no reversal of inhibition was observed by
      increasing the antigen concentration. The data here presented demonstrate that
      short curses of high dose betamethasone specifically impair antigen presentation.
      Thus, this mechanism appears to be involved in the immunosuppressant activity of
      betamethasone.

PMID- 7723589
TI  - Lidocaine does not prevent the calcium paradox in rat hearts: a laser microprobe
      mass analysis (LAMMA) study.
AB  - The calcium paradox stands for the cell damage that occurs when isolated hearts
      are perfused with a Ca(2+)-free solution followed by perfusion with a Ca(2+)
      containing solution. Although it is generally accepted that a massive Ca2+ influx
      during the Ca(2+)-repletion phase is responsible for the cell damage, there is no
      consensus about what makes the heart susceptible to the calcium paradox during
      the Ca(2+)-depletion phase. It has been suggested that the extent of the calcium
      paradox is primarily determined by accumulation of Na+ during Ca2+ depletion and
      a subsequent accumulation of Ca2+ via reverse Na(+)-Ca2+ exchange during Ca2+
      repletion. According to another theory, weakening of intercalated disc junctions
      during Ca2+ depletion and contracture-mediated disruption of the cell membrane
      during Ca2+ repletion are responsible for the calcium paradox. In the present
      study we further investigated the possible role of Na+ in the development of the
      calcium paradox. During Ca2+ depletion, lidocaine was used to inhibit Na+ entry
      through the Na+ channels. Isolated rat hearts were perfused with Krebs Henseleit
      buffer (KH) containing 1.4 mM Ca2+ for 15 min, followed by 10 min of Ca(2+)-free
      perfusion and 10 min of reperfusion with Ca2+. In the treated group 0.1 mM
      lidocaine was present throughout the experiment. At the end of each experiment,
      Ca2+ cytochemistry was performed and the intracellular Ca2+ content was analyzed
      by laser microprobe mass analysis (LAMMA). The results show that during Ca2+
      depletion, the intracellular Ca2+ content did not change significantly. Ca2+
      repletion, however, gave rise to a full calcium paradox irrespective of the
      presence of lidocaine: massive cell damage and Ca2+ accumulation in the
      mitochondria. The results provide further evidence that intracellular Na+
      accumulation during Ca2+ depletion is not involved in the occurrence of the
      calcium paradox.

PMID- 7723590
TI  - ATP enhances catecholamine uptake into PC12 cells.
AB  - Catecholamine uptake into PC12 cells, in the presence and absence of ATP, was
      measured in a bicarbonate-buffered Krebs Ringer. ATP enhanced significantly the
      uptake in a dose-dependent manner with maximal uptake at 1-3 mM. ATP increased
      the Vmax of uptake by 3-5 fold for both dopamine and norepinephrine, without a
      significant change in the Km. ATP-stimulated amine uptake was temperature- and
      Na(+)-dependent and robust in bicarbonate, but not in HEPES buffer. The ability
      to enhance uptake was not observed with metabolites of ATP. GTP and UTP were
      equally effective to ATP in enhancing CA uptake. This uptake was less sensitive
      to uptake inhibitors in bicarbonate buffered media than in phosphate-buffered
      media, and more so in the presence of ATP. It is suggested that ATP is an
      allosteric modulator of the transporter and that a stable ATP analog, with ATP
      like enhancement of dopamine uptake, may be an effective cocaine antagonist.

PMID- 7723591
TI  - Maturation status of small intestine epithelium in rats deprived of dietary
      nucleotides.
AB  - We describe the changes of several brush-border enzymatic activities in different
      subpopulations of epithelial cells, separated sequentially from the villus tip-to
      crypt axis of the small intestine, induced by deprivation of dietary nucleotides
      for different periods of time in adult rats. Deprivation of dietary nucleotides
      lead to a decrease in the content and specific activity of alkaline phosphatase,
      leucine-aminopeptidase, maltase, sucrase and lactase in the villus tip, but had
      little effect on the crypt zone. The effect of the nucleotide deprivation on the
      enzymatic activity progressively increased towards the tip of the villus. Since
      these enzymes are maturation markers of the intestinal cells, these results
      support the idea that dietary nucleotides affect the maturation status of small
      intestine epithelium.

PMID- 7723592
TI  - Glucose oxidation and monoamine oxidase activity from the fibroblasts of
      schizophrenic patients and controls.
AB  - Fibroblasts have emerged as one of the best systems in which to study several
      genetically inherited diseases. Their use avoids the contaminating effects of
      medication and other environmental factors. Moreover, fibroblast cells cultured
      in vitro can express several biochemical parameters which are characteristic of
      neuronal cells. We have studied fibroblast MAO-A and glucose oxidation and
      platelet MAO-B from schizophrenic patients and control subjects. Fibroblasts from
      schizophrenics showed an increased glucose oxidation in two different experiments
      conducted (122% and 126% compared to controls). No changes were found in the
      levels of fibroblast MAO-A or platelet MAO-B activity. Possibly these alterations
      in glucose oxidation may be associated with a generalized membrane abnormality
      which has been reported in schizophrenia.

PMID- 7723593
TI  - Down-regulation of Th2 cell-mediated murine peritoneal eosinophilia by
      antiallergic agents.
AB  - Local eosinophilia has been linked to the pathogenesis of the inflammatory aspect
      of allergic diseases. The present study found that co-injection of D10G4.1 (D10)
      cells, a murine Th2 clone, with conalbumin (CA) into the peritoneal cavity of
      AKR/J mice increased the number of peritoneal eosinophils. The accumulation of
      eosinophils reached a maximum level at 24 to 48 hr and was accompanied by a
      marked increase in the number of neutrophils and a minor increase in the number
      of mononuclear cells. D10-induced peritoneal eosinophilia was suppressed by
      administration of either anti-IL-4 and anti-IL-5 monoclonal antibodies in an
      additive manner or by cyclosporin A (CsA). Interestingly, suplatast tosilate (IPD
      1151T), known to be antiallergic agent capable of suppressing IgE synthesis and
      chemical mediator release, but not disodium cromoglycate, selectively suppressed
      eosinophil accumulation. Taken together with the observation that CsA and IPD
      1151T suppressed IL-4 and IL-5 production by CA-stimulated D10 cells in vitro,
      the present results strongly suggest that agents capable of down-regulating Th2
      cell cytokine production may attenuate allergic inflammation by impairing the
      recruitment of eosinophils that is mediated by Th2 cells.

PMID- 7723594
TI  - Effect of angiotensin II receptor blocker on angiotensin II stimulated DNA
      synthesis of cultured human aortic smooth muscle cells.
AB  - To examine the role of the renin-angiotensin system on human vascular smooth
      muscle cell (VSMC) replication, we studied the effect of DUP 753, an angiotensin
      II (ANG II) type 1 receptor antagonist, on ANG II stimulated tritiated-thymidine
      (3H-Tdr) incorporation into cultured human aortic VSMC. ANG II stimulated DNA
      synthesis of VSMC in a dose-dependent manner as estimated by 3H-Tdr incorporation
      (control; 2993 +/- 486 cpm, 10(-8)M; 3360 +/- 350 cpm, 10(-7)M; 3474 +/- 516 cpm,
      10(-6)M; 4889 +/- 320 cpm, P < 0.01). The effects of ANG II were clearly
      inhibited by 10(-7) M DUP 753 (ANG II 10(-8) M; 3360 +/- 350 vs 509 +/- 39 cpm,
      10(-7) M; 3474 +/- 516 vs 661 +/- 36 cpm, 10(-6) M; 4889 +/- 320 vs 806 +/- 76
      cpm, each P < 0.01). This receptor antagonist decreased the basal 3H-Tdr
      incorporation of VSMC from 2933 +/- 486 to 411 +/- 78 cpm (P < 0.01).
      Furthermore, DUP 753 decreased 10(-7) M ANG II-stimulated 3H-Tdr incorporation of
      VSMC in a dose-dependent manner (control; 2627 +/- 256 cpm, 10(-9) M; 2145 +/-
      143 cpm, 10(-8) M; 1047 +/- 543 cpm, 10(-7) M; 639 +/- 169 cpm, 10(-6) M; 642 +/-
      59 cpm, P < 0.01). These observations suggest that, in human VSMC, ANG II type 1
      receptors are important for the regulation of both stimulated and basal cell
      proliferation. It may therefore be worth while to examine the clinical usefulness
      of DUP 753 for preventing abnormal VSMC growth.

PMID- 7723595
TI  - Zymosan-induced arthritis in rats. II. Effects of anti-inflammatory drugs.
AB  - As zymosan-induced arthritis in rats combines dual activation of early
      prostaglandin-dependent processes (edema, fever, pain) and IL-1 related effects
      on cartilage metabolism, we compared the respective influences of indomethacin
      (IMT) and dexamethasone (DEX) on its course. Different parameters were assessed:
      knee swelling, febrile response, loss of activity, cartilage metabolism and
      histology. DEX improved all these parameters, while IMT exerted only light
      beneficial effects on fever and knee swelling without obvious beneficial
      influence on cartilage metabolism and histological lesions. These results suggest
      that anti-inflammatory activities of DEX and IMT are due to interferences with
      different pathways during zymosan-induced arthritis in rats.

PMID- 7723597
TI  - Intrauterine exposure to cocaine increased plasma ANP (atrial natriuretic
      peptide) but did not alter hypoxanthine concentrations in the sheep fetus.
AB  - To assess the effects of cocaine, administered to the ewe, on the secretion of
      atrial natriuretic peptide (ANP), Plasma Renin Activity (PRA) and hypoxanthine in
      the fetus we studied 6 chronically cannulated sheep fetuses late in gestation.
      The ewe was given an intravenous injection of cocaine (2 mg/kg). Maternal and
      fetal arterial blood samples were withdrawn prior to the injection and at 2, 5,
      10, 15, 45 and 60 min after the injection for the measurement of ANP, PRA and
      hypoxanthine. Fetal arterial blood pressure (MAP), plasma ANP and protein levels
      increased and pH and pO2 decreased after cocaine was administered to the ewe.
      Fetal plasma hypoxanthine and PRA did not change. These results suggest that
      cocaine administration to the ewe is associated with fetal hypertension,
      hypoxemia and acidemia all of which may serve as stimuli for the secretion of
      ANP.

PMID- 7723596
TI  - GABAA receptor activation induces GABA and glutamate release from preoptic area.
AB  - The effect of GABA receptor agonists on release in vitro of radiolabeled GABA and
      glutamate was studied using a crude preparation of isolated nerve terminals
      (neurosomes). GABA agonists were incubated (2 min, 37 degrees C) with neurosomes
      prepared from hypothalamus, preoptic area (POA) and frontal cortex tissues. Under
      these conditions, GABA and the GABAA receptor agonist muscimol, but not the GABAB
      receptor agonist baclofen, stimulated 3H-GABA and 3H-glutamate release from POA
      but not hypothalamic or cortical neurosomes of gonadally intact male rats. These
      effects were inhibited by the GABAA receptor antagonists picrotoxin, bicuculline
      and SR-95531. Significant efflux of 3H-glutamate could be elicited from cortical
      neurosomes following longer (5 min) incubations with 500 microM GABA and 400
      microM muscimol. Muscimol-induced release of 3H-glutamate and 3H-GABA was
      dependent on extracellular calcium. Muscimol and GABA failed to release 3H-GABA
      or 3H-glutamate from POA neurosomes of ovariectomized female rats. However,
      administration of estradiol and progesterone to ovariectomized females prior to
      sacrifice caused the appearance of muscimol induced-release of amino acids from
      POA neurosomes comparable to that obtained in male rats. GABA-induced release of
      3H-glutamate was similarly dependent on pretreatment of ovariectomized rats with
      ovarian steroids. GABAA receptor-induced release of amino acids is therefore
      brain region-specific and modified by hormonal status.

PMID- 7723598
TI  - Type II and type IIB activin receptors in human placenta.
AB  - The expression of type II activin receptor(ActRII) and type IIB activin
      receptor(ActRIIB) messenger RNA(mRNA) in different stages of development of the
      human placenta was examined by Northern blot analysis. In our experiments, the
      first trimester placenta showed the highest levels of ActRIIB expression and
      human placenta from different stages expressed both type II and IIB activin
      receptor mRNAs. These observations support the hypothesis that activin might act
      as a paracrine/autocrine factor in human placenta and activin might have stage
      specific functions through the different types of receptors.

PMID- 7723599
TI  - Pyrroloquinoline quinone (PQQ) inhibits the expression of tyrosinase mRNA by
      alpha-melanocyte stimulating hormone in murine B16 melanoma cells.
AB  - The biological functions of pyrroloquinoline quinone (PQQ), a bacterial redox
      coenzyme and potent radical scavenger, have not been elucidated in mammals. In
      this paper, we studied the effects of PQQ on tyrosinase activity and subsequent
      melanogenesis in murine B16-F10 melanoma and found that alpha-Melanocyte
      stimulating hormone (MSH)-induced melanogenesis was inhibited by 6.3 to 25 microM
      PQQ in a dose-dependent manner. Moreover, PQQ inhibited MSH-induced tyrosinase
      activity by suppressing tyrosinase mRNA expressed by MSH. However, PQQ had no
      effect on MSH-stimulated cyclic adenosine 3', 5'-monophosphate (cAMP) production.
      These observations suggest that PQQ inhibits the expression of tyrosinase mRNA at
      a post receptor level and that PQQ may be useful in investigating hormone actions
      mediated by cAMP.

PMID- 7723600
TI  - Norharman-induced changes of extracellular concentrations of dopamine in the
      nucleus accumbens of rats.
AB  - In vivo microdialysis was used to investigate the effects of acute injections of
      norharman on extraneuronal concentrations of dopamine (DA) in the nucleus
      accumbens of rats. Administration of norharman (2.44 and 43.97 mumol/kg, i.p.)
      elicited an increase of the DA efflux by 70% and 160% respectively which returned
      to basal levels after 120 and 160 min respectively. In contrast, administration
      of an intermediate dose of norharman (7.33 umol/kg, i.p.) elicited a significant
      decrease to 72% of basal level. These findings indicate that norharman alters the
      activity of mesolimbic dopaminergic neurons in an U-shape manner. The
      observations further suggest several receptor mechanisms mediating the effects of
      norharman.

PMID- 7723601
TI  - Enhancement of hepatic glucose release and bile flow by the phosphodiesterase-III
      inhibitor enoximone in the perfused rat liver.
AB  - The use of phosphodiesterase-III-inhibitors (PDI) as inotropic substances in the
      treatment of cardiac failure can be associated with hyperglycaemia. This
      phenomenon could be caused by hepatic events induced by PDI. The purpose of our
      study was to investigate the effects of the PDI enoximone on hepatic carbohydrate
      metabolism and bile flow. In the rat liver perfusion model, hepatic glucose and
      lactate production, portal flow and bile flow were determined. Administration of
      enoximone (1, 10, 100 microM) increased hepatic glucose output and bile acid
      independent bile flow in a dose-dependent manner. The PDI enhanced the
      glycogenolytic effects of glucagon (from 15.7 to 38.6 mumol glucose/g/20 min), of
      epinephrine (from 7.1 to 38.7 mumol glucose/g/20 min), of norepinephrine (from
      9.8 to 32 mumol/g/20 min) and of phenylephrine (from 25.5 to 40.8 mumol
      glucose/g/20 min). Furthermore, lactate production was significantly reduced by
      enoximone. The effect of epinephrine and phenylephrine on portal flow was blocked
      or diminished by enoximone administration. In summary, it was shown that the PDI
      enoximone is able to enhance hepatic glucose production. Bile acid-independent
      bile flow was increased by the inhibition of phosphodiesterase-III. The effects
      of enoximone and glycogenolytic hormones on glucose release were synergistic. The
      vasoconstrictive action of catecholamines was reduced or completely prevented by
      enoximone. In conclusion, enoximone has glycogenolytic, vasodilatory and
      choleretic properties in the liver.

PMID- 7723602
TI  - Corticosterone secretion in response to serotonin and ACTH by perfused adrenal of
      normal and athymic nude mice.
AB  - Adrenocortical secretory responses to chemical mediators and ACTH in CD1 ICR
      nu/nu (athymic) mice were compared with those in CD1 ICR (normal) mice. The
      bilateral adrenals of normal or athymic mice were perfused in situ with
      artificial medium equilibrated by 95% O2 + 5% CO2. Infusion of serotonin induced
      the secretory response of corticosterone significantly at 10 nM and markedly at
      100 nM and the response at 1000 or 10000 nM declined as compared with that at
      100nM in normal mice. Total corticosterone secretion in response to 100 or 1000
      nM serotonin in athymic mice was about one fourth that in normal mice,
      respectively. Corticosterone responses to ACTH at the range of 10 to 300 pg/ml in
      athymic mice were comparable to those in normal mice. Infusion of histamine,
      platelet activating factor(PAF), or compound 48/80 did not induce significant
      corticosterone response in both normal and athymic mice. The data suggest that
      the congenital defect of the thymus and/or hair causes the hyporesponsiveness of
      adrenocortical cells to serotonin although the adrenal cortex of athymic mice is
      able to perform its function in response to ACTH.

PMID- 7723603
TI  - Monoamine release in the rat striatum is induced by delta-guanidinovaleric acid
      and inhibited by GABA agonists.
AB  - delta-Guanidinovaleric acid (GVA) is an endogenous convulsant and is thought to
      be a specific gamma-aminobutyric acid (GABA) antagonist. In this study, we
      examined the effects of GVA and GABA agonists, GABA, muscimol and baclofen, on
      the release of dopamine (DA) and serotonin (5-HT) in the rat striatum using a
      brain dialysis technique. GVA produced a significant increase in the amount of DA
      and 5-HT released compared with controls. Both GABA (10mM) and muscimol (10mM)
      inhibited the GVA-induced release of DA and 5-HT. Muscimol was a more potent
      inhibitor of 5-HT release than DA release. Baclofen (10mM) inhibited only the GVA
      induced DA release. These results suggest that the activation of GABA receptors
      inhibits the release of DA and 5-HT in the striatum, and that the dopaminergic
      system regulates GABA-B receptors and the serotonergic system mainly regulates
      GABA-A receptors.

PMID- 7723604
TI  - Caring for the morbidly obese pregnant woman.

PMID- 7723605
TI  - Guardianship and the refusal of treatment.

PMID- 7723607
TI  - Research or else.

PMID- 7723608
TI  - AIDS among migrant farmers.

PMID- 7723606
TI  - Tender beginnings: good idea.

PMID- 7723609
TI  - Free access to electronic AIDS information.

PMID- 7723610
TI  - Zidovudine in pregnancy.

PMID- 7723611
TI  - Evaluating case management programs.

PMID- 7723612
TI  - Tender beginnings: good idea.

PMID- 7723614
TI  - Anger in women as an emerging issue in MCH.

PMID- 7723613
TI  - Diagnosis and management of pyelonephritis in infants.

PMID- 7723615
TI  - Does tympanic temperature measure up?

PMID- 7723617
TI  - Modulation of serotonin and corticosteroid receptor gene expression in the rat
      hippocampus with circadian rhythm and stress.
AB  - Glucocorticoids and serotonin (5-HT) modulate behaviour and hypothalamic
      pituitary-adrenal (HPA) axis responses. The two systems interact prominently in
      the hippocampus, where these effects may occur. We have previously shown that
      hippocampal 5-HT2C receptor mRNA expression is increased by adrenalectomy or
      central 5-HT lesions. We have now determined expression of corticosteroid and 5
      HT receptor subtype genes in the hippocampus across the diurnal cycle, when there
      are changes both in plasma corticosterone and hippocampal 5-HT levels, as well as
      the responses of these transcripts to acute and chronic stress, using in situ
      hybridisation histochemistry. Expression of both glucocorticoid (GR) and
      mineralocorticoid (MR) receptor mRNAs was significantly higher (131-153%) in the
      hippocampus at 08.00 h (corticosterone nadir) than at 20.00 h (corticosterone
      peak). 5-HT2C receptor mRNA expression also showed circadian variation (106-184%
      higher in CA1-CA3 in the morning). Hippocampal 5-HT1A and 5-HT2A receptor mRNA
      expression had no diurnal variation. Chronic (15 day) adjuvant arthritis stress,
      abolished the circadian corticosterone nadir, maintaining plasma corticosterone
      around diurnal peak values. Chronic arthritis stress suppressed hippocampal 5
      HT2C receptor mRNA expression at 08.00 h to levels comparable to 20.00 h
      controls. By contrast to chronic stress, 6 h after acute laparotomy stress,
      plasma corticosterone was elevated above control (20.00 h) and 5-HT2C receptor
      mRNA expression was increased (CA2). Neither acute nor chronic stress altered MR,
      GR, 5-HT1A or 5-HT2A receptor mRNA expression in any hippocampal subfield. These
      results show that hippocampal expression of the 5-HT2C receptor gene, but not
      other subtypes, is sensitive to a variety of manipulations.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7723616
TI  - Changes in growth inhibitory factor mRNA expression compared with those in c-jun
      mRNA expression following facial nerve transection.
AB  - We investigated growth inhibitory factor (GIF) mRNA expression within the rat
      facial nucleus with the aid of in situ hybridization. We found that GIF mRNA was
      expressed abundantly in the facial motoneurons of sham operated animals, and that
      this gene expression decreased after transection of the facial nerve. This
      decrease of GIF mRNA was first detected on the third day and was maintained for
      at least five weeks after transection of the nerve. Changes in c-jun, an
      immediate early gene, were also investigated with this model, and it was found
      that c-jun mRNA started to increase in the facial nucleus on the first day and
      that this increase was maintained for at least 5 weeks. These results suggest
      that the facial motoneurons, when their axons are transected, continuously
      respond to the injury and that GIF mRNA is actively suppressed to reduce the
      inhibition of neurite outgrowth in order to regenerate the axons.

PMID- 7723618
TI  - Diurnal variation in kainate-induced AP-1 activation in rat brain: influence of
      glucocorticoids.
AB  - The large diurnal rhythm of circulating glucocorticoid levels was used to
      determine if physiological fluctuations of glucocorticoids were capable of
      modulating kainate-induced immediate early gene (IEG) activation, measured as AP
      1 DNA binding activity, in rat brain since administered dexamethasone previously
      had been shown to be inhibitory. AP-1 activity in the cerebral cortex 1.5 h after
      kainate treatment measured at 08.00 h (4.9-fold control) was more than twice the
      stimulation obtained at 16.00 h (1.8-fold). These times of day are associated
      with reported low and high levels of circulating glucocorticoids at 08.00 and
      16.00 h, respectively. To test if there was a causal relationship, kainate
      induced AP-1 activity was measured at both times in adrenalectomized rats.
      Adrenalectomy abolished the attenuation of the response to kainate found in
      intact rats at 16.00 h, indicating that the diurnal fluctuations in circulating
      glucocorticoids contribute to modulation of IEG responses to kainate. Neither AP
      1 activity in the hippocampus nor cyclic AMP response element activation in
      either brain region measured after kainate treatment was influenced by the time
      of day or by adrenalectomy. Immunoprecipitation of glucocorticoid receptors from
      cortical nuclear extracts co-precipitated c-Jun, indicating that the mechanism
      accounting for the suppression of AP-1 activity by glucocorticoids may involve
      direct interactions between activated glucocorticoid receptors and AP-1
      constituent proteins. These results extend previous reports that administered
      glucocorticoids inhibit AP-1 activity by demonstrating that this occurs with
      endogenous glucocorticoids as a consequence of the circadian rhythm of
      circulating glucocorticoids and demonstrate that responses to kainate vary
      dependent upon the time of day.

PMID- 7723619
TI  - Cloning and expression of SEZ-6, a brain-specific and seizure-related cDNA.
AB  - To clarify the molecular mechanism of neuronal bursting activity of seizures, we
      have constructed a cDNA library from mouse cerebrum cortex-derived cells treated
      with pentylentetrazole (PTZ), one of the convulsant drugs. Using a differential
      screening technique, several cDNA clones whose expressions change with PTZ
      treatment were obtained. Among these clones, SEZ-6 was characterized by increased
      expression with PTZ. Detailed northern analysis showed that expression of SEZ-6
      was limited to the brain and increased by the administration of PTZ not only in
      in vitro cultured cells but also in vivo. Analysis of SEZ-6 cDNA revealed
      multiple motifs, including typical signal sequence, threonine-rich domain, five
      copies of short consensus repeats (SCRs) or sushi domain (complement C3b/C4b
      binding site), two repeated sequences which were partially similar to the CUB
      domain or complement C1r/s-like repeat, one transmembrane domain and a short
      cytoplasmic segment in the C-terminal region. Although many proteins with
      multiple SCRs or CUB domains other than complement-related proteins have been
      found, this is the first report about a brain-specific cDNA which encodes
      membrane protein with both SCRs and CUB domain-like segments. Based on these
      findings, it is evident that SEZ-6 encodes a novel type of protein which may be
      related to seizure.

PMID- 7723620
TI  - The neonatal lesion of the meso-telencephalic dopaminergic pathway increases
      intrastriatal D2 receptor levels and synthesis and this effect is reversed by
      neonatal dopaminergic rich-graft.
AB  - The ascending dopaminergic pathway of 3-day-old rats has been unilaterally
      destroyed by the injection of 6-hydroxydopamine into the lateral hypothalamus.
      Five days later, a suspension containing embryonic dopaminergic neurones was
      injected in the lesioned neostriatum. Rotational responses to dopaminergic
      agonists were tested eight months after grafting and animals were killed one
      month later. Neostriatal dopaminergic D1 and D2 receptors were examined using
      autoradiography while changes in D2 receptor mRNA levels were studied by in situ
      hybridization. The lesion induced a behavioural hypersensitivity - as manifested
      in contralateral rotations - to dopaminergic D1 (SKF 38393) or D2 (LY 171555)
      agonists which was abolished by the graft. Density of D1 receptors was not
      affected by the lesion while D2 receptors density was increased by 20-25% in the
      more rostral part of the neostriatum. Changes in D2 mRNA after the lesion
      paralleled those observed for D2 receptor density, i.e. D2 mRNA level was
      increased by 15-19% in the rostral neostriatum. The graft did not influence D1
      receptor densities but reversed the post-lesion increase of D2 receptors
      associated parameters. It is concluded that dopaminergic grafts implanted in
      neonatal hosts are able to normalise the density of D2 receptors by an action on
      their synthesis.

PMID- 7723621
TI  - Noradrenergic regulation of immediate early gene expression in rat forebrain:
      differential effects of alpha 1- and alpha 2-adrenoceptor drugs.
AB  - Noradrenergic (NAergic) transmission in the rat cerebral cortex has recently been
      shown to be involved in the regulation of the basal expression of NGFI-A, an
      immediate early gene (IEG) which encodes a zinc-finger transcription factor. The
      present study further investigated the role of the NAergic system in mediating
      cortical IEG expression and possible topographical changes in expression of NGFI
      A mRNA in rat forebrain after alpha 1- and alpha 2-adrenoceptor (AR) agonist and
      antagonist treatment. Expression of c-fos and c-jun, which encode leucine-zipper
      class transcription factors, was also studied. Male Sprague-Dawley rats were
      injected intraperitoneally with either an alpha 1-AR agonist (methoxamine, 5 or
      10 mg/kg); an alpha 1-AR antagonist (prazosin, 5 mg/kg); an alpha 2-AR agonist
      (clonidine, 0.5 mg/kg); or an alpha 2-AR antagonist (methoxyidazoxan, 5 mg/kg)
      and killed after 1 h. IEG mRNA levels were detected by quantitative in situ
      hybridization histochemistry using 35S-labelled oligonucleotides. High basal
      levels of NGFI-A mRNA were present in cortical layers IV and VI, hippocampal CA1,
      piriform cortex, amygdala and caudate putamen. alpha 1-AR agonist and antagonist
      treatment had essentially no effect on IEG mRNA, despite producing characteristic
      behavioral and peripheral effects at the doses used. Methoxyidazoxan
      significantly increased (mean%) NGFI-A mRNA in: cerebral cortex (44); caudate
      putamen (82); amygdala (92); and CA1 of hippocampus (48), while clonidine
      significantly decreased NGFI-A mRNA in the various cortical layers to a similar
      extent (27-37%). Basal c-fos mRNA expression was lower than that for NGFI-A in
      forebrain areas including cortex, caudate putamen and hippocampus.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7723622
TI  - NGFR-mRNA expression in sciatic nerve: a sensitive indicator of early stages of
      axonopathy.
AB  - Expression of the low-affinity nerve growth factor receptor (NGFR) in the sciatic
      nerve (particularly Schwann cells) is high during development but is
      downregulated upon establishment of the mature axon-Schwann cell relationship.
      NGFR is re-expressed by Schwann cells if this relationship is altered by
      degeneration of axons (axotomy) or myelin (tellurium intoxication). To determine
      the sensitivity of NGFR expression to axonal injury, we have assayed NGFR-mRNA
      levels in proximal and distal regions of nerves exposed to the axonopathic agents
      acrylamide and isoniazid, as well as in proximal and distal stumps of axotomized
      nerves. NGFR-mRNA was elevated in all three models and correlated regionally with
      sites of axonal perturbation. In distal regions of acrylamide- and isoniazid
      intoxicated nerves, NGFR-mRNA was elevated at least 2 days prior to visible signs
      of axonal degeneration as assayed by morphological techniques utilizing light
      microscopy. NGFR-mRNA was also elevated in proximal regions of axotomized and
      acrylamide-intoxicated nerves prior to signs of axonal degeneration. In these
      models, increased mRNA expression correlated with alterations in the size
      distribution of axonal cross sections. The common response in all of these
      situations indicates that NGFR expression, in addition to being a marker for
      axonal degeneration, is also a sensitive indicator of less profound perturbations
      in normal axon-Schwann cell interactions, including early stages of axonopathy.
      We suggest that assay for NGFR-mRNA may be utilized as a rapid and simple method
      (relative to more labor-intensive morphological methods) to screen for peripheral
      neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723623
TI  - GABAA, GABAC, and NMDA receptor subunit expression in the suprachiasmatic nucleus
      and other brain regions.
AB  - Identification of the neurotransmitter receptor subtypes within the
      suprachiasmatic nuclei (SCN) will further understanding of the mechanism of the
      biological clock and may provide targets to manipulate circadian rhythms
      pharmacologically. We have focused on the ionotropic GABA and glutamate receptors
      because these appear to account for the majority of synaptic communication in the
      SCN. Of the 15 genes known to code for GABA receptor subunits in mammals we have
      examined the expression of 12 in the SCN, neglecting only the alpha 6, gamma 3,
      and rho 2 subunits. Among glutamate receptors, we have focused on the five known
      genes coding for the NMDA receptor subunits, and two subunits which help comprise
      the kainate-selective receptors. Expression was characterized by Northern
      analysis with RNA purified from a large number of mouse SCN and compared to
      expression in the remaining hypothalamus, cortex and cerebellum. This approach
      provided a uniform source of RNA to generate many replicate blots, each of which
      was probed repeatedly. The most abundant GABA receptor subunit mRNAs in the SCN
      were alpha 2, alpha 5, beta 1, beta 3, gamma 1 and gamma 2. The rho 1 (rho 1)
      subunit, which produces GABAC pharmacology, was expressed primarily in the retina
      in three different species and was not detectable in the mouse SCN despite a
      common embryological origin with the retina. For several GABA subunits we
      detected additional mRNA species not previously described. High expression of
      both genes coding for glutamic acid decarboxylase (GAD65 and GAD67) was also
      found in the SCN. Among the NMDA receptor subunits, NR1 was most highly expressed
      in the SCN followed in order of abundance by NR2B, NR2A, NR2C and NR2D. In
      addition, both GluR5 and GluR6 show clear expression in the SCN, with GluR5 being
      the most SCN specific. This approach provides a simple measure of receptor
      subtype expression, complements in situ hybridization studies, and may suggest
      novel isoforms of known subunits.

PMID- 7723625
TI  - Transcript distribution of plasma membrane Ca2+ pump isoforms and splice variants
      in the human brain.
AB  - Plasma membrane calcium pumps (PMCAs) play a major role in the maintenance and
      fine regulation of the intracellular Ca2+ concentration. Fourteen subregions of
      the normal human brain were carefully dissected and analyzed by reverse
      transcriptase-polymerase chain reaction for the distribution of mRNAs
      corresponding to the four known PMCA genes as well as their alternative splicing
      products at two previously defined 'hotspots' A and C. All PMCA genes were found
      to be expressed in every brain subregion; however, consistent differences were
      found in the distribution of alternative splice options. The four cortical
      regions and hippocampus were characterized by the relative preference of variants
      that include an entire exon at site C and lead to the expression of isoforms of
      the a-type. Inferior olive and olfactory bulb showed a relative preponderance of
      the b-form 'default' types of alternative splicing at site C, and a decrease or
      even the lack of 'differentiated' forms such as variants 1a and 1c. At the N
      terminal splice site A, the default x-type variants were predominant in all brain
      regions for PMCA 1, 3, and 4. By contrast, the pattern of PMCA2 variants was the
      most variable, ranging from the presence of the entire set of 2x, 2w, and 2z
      forms in inferior olive to the almost exclusive presence of form 2z (excluding
      all alternatively spliced sequences) in the four cortical regions, caudate, and
      hippocampus. Regional differences in the PMCA splice type distribution in normal
      human brain may correlate with different demands on the regulation of the set
      point resting Ca2+ levels in these areas. Changes in these patterns may correlate
      with altered physiological states of the affected regions and/or reflect an
      (early) sign of Ca2+ dyshomeostasis characteristic of many neurodegenerative
      diseases.

PMID- 7723624
TI  - Estrogen regulates preproenkephalin-A mRNA levels in the rat ventromedial
      nucleus: temporal and cellular aspects.
AB  - Numerous studies suggest that the ventromedial nucleus of the hypothalamus is a
      primary locus of control for reproductive behavior in the female rat. The display
      of lordosis behavior is estrogen dependent and its regulation appears to involve
      the activity of endogenous opioid circuits in the mediobasal hypothalamus and
      brainstem. Hypothalamic levels of preproenkephalin-A mRNA and the neuropeptide
      which it encodes, methionine-enkephalin, are dramatically up-regulated by
      estrogen. To characterize the temporal and cellular aspects of the effect of an
      acute exposure to estrogen on preproenkephalin-A mRNA levels in the ventromedial
      nucleus and arcuate nucleus of the hypothalamus, ovariectomized female rats were
      injected with 50 micrograms estradiol benzoate and used for quantitative in situ
      hybridization histochemistry of preproenkephalin-A mRNA. In the ventromedial
      nucleus, estrogen treatment caused a biphasic increase in the number of
      preproenkephalin-A mRNA cells. Maximal numbers of cells expressing
      preproenkephalin-A mRNA were observed at 1 and 48 h after estrogen injection. At
      4 and 96 h after estrogen injection, the numbers of preproenkephalin-A mRNA cells
      were similar to that which was seen in the ovariectomized female. The induction
      of preproenkephalin-A mRNA expression in cells of the arcuate nucleus followed a
      similar pattern that peaked 48 h after exposure to estrogen. Levels of
      preproenkephalin-A mRNA per cell did not change in either nucleus as a function
      of estrogen treatment. Thus, acute estrogen treatment induces expression of
      preproenkephalin-A mRNA in populations of cells in the ventromedial hypothalamus
      and arcuate nucleus in which preproenkephalin-A mRNA expression is undetectable
      by in situ hybridization in the absence of circulating estrogen.

PMID- 7723626
TI  - Isolation and expression analysis of tyro3, a murine growth factor receptor
      tyrosine kinase preferentially expressed in adult brain.
AB  - Growth factors and their receptors function in the nervous system to induce
      proliferation and differentiation of neuronal precursor cells and to support
      survival of mature neurons. We have isolated a murine growth factor receptor
      tyrosine kinase using an anti-phosphotyrosine antibody screening procedure and
      studied the pattern of expression. The deduced amino acid sequence of the kinase
      has all the characteristics of a growth factor receptor and consists of a
      putative extracellular domain, a transmembrane domain, and a tyrosine kinase
      domain. Sequence comparison with known receptor tyrosine kinases indicated that
      the murine kinase is a mouse homolog of tyro3. tyro3 belongs to the Axl/Ufo
      growth factor receptor family. In the putative extracellular domain, there are
      two Ig-like domains and two fibronectin type III repeats which are conserved in
      other members of the Axl/Ufo family receptors. Northern blot hybridization
      analysis showed that tyro3 is expressed at high levels in the brain of adult
      mice, although considerable expression was also observed in the testis. In situ
      hybridization analysis revealed that high levels of tyro3 are expressed in the
      cerebral cortex, the lateral septum, the hippocampus, the olfactory bulb, and in
      the cerebellum. The highest levels of tyro3 expression in the brain are
      associated with neurons. The preferential expression of tyro3 in specific regions
      of the adult mouse brain suggests that tyro3 may function as a novel neurotrophic
      factor receptor.

PMID- 7723627
TI  - Point mutations of mitochondrial genome in Parkinson's disease.
AB  - Oxidative stress and subsequent energy crisis have been proposed as the cause of
      nigral neuronal cell death in Parkinson's disease. We have reported defects in
      the mitochondrial respiratory chain and increased amount of deleted mitochondrial
      genome in the nigrostriatal system of patients with Parkinson's disease. Deletion
      in mitochondrial DNA could be ascribed to somatically acquired premature aging
      leading to cell death. To elucidate the contribution of maternally transmitted
      point mutations in mitochondrial DNA to the premature DNA damages, we employed a
      direct sequencing system and analyzed the total nucleotide sequences of
      mitochondrial DNA in the brains of five patients with idiopathic Parkinson's
      disease. There were no predominant point mutations among the patients in contrast
      to some neuromuscular diseases. However, each patient had several point mutations
      that would result in a significant change in the gene products. Some of these
      mutations may be involved either in the increased production of oxygen radicals
      from the mitochondrial respiratory chain or in the increased susceptibility of
      the respiratory chain components to oxidative damage. We propose that some of
      these mutations can be regarded as one of the risk factors accelerating
      degeneration of nigrostriatal pathway in Parkinson's disease.

PMID- 7723628
TI  - Localization of parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP
      receptor mRNAs in rat brain.
AB  - Parathyroid hormone (PTH)-related peptide (PTHrP) has been identified in human
      tumors associated with the syndrome of humoral hypercalcemia of malignancy. PTHrP
      mRNA is also expressed in a variety of non-malignant tissues, suggesting that
      PTHrP is an endogenous peptide with as-yet unidentified autocrine or paracrine
      functions in normal tissues, including brain (Weir et al., Proc. Natl. Acad.
      Sci., 87 (1990) 108-112). In the present study, we used in situ hybridization to
      examine the expression of PTHrP and the common receptor for PTH and PTHrP in
      adult rat brain. Widespread yet anatomically discrete patterns of hybridization
      were observed using 35S-labeled antisense cRNA probes. PTHrP gene expression was
      highest in the supramamillary nucleus of the hypothalamus, medial superior
      olivary nucleus, and in subpopulations of cells in the neostriatum, hippocampus,
      and cerebral cortex. Other major sites of PTHrP gene expression included the
      amygdala, midline thalamic nuclei, pontine nuclei, choroid plexus, and the
      anterior pituitary gland. Highest levels of PTH/PTHrP receptor mRNA were in the
      mesencephalic portion of the trigeminal nucleus and the trigeminal ganglion, the
      lateral reticular, pontine and reticulotegmental nuclei, the hypoglossal nucleus
      and area postrema. Other major sites of PTH/PTHrP receptor expression included
      the anterodorsal nucleus of the thalamus, basolateral amygdala, entorhinal
      cortex, parasubiculum, cells in the Purkinje cell layer of the cerebellum,
      vestibular nuclei, ventral cochlear nucleus, the motor nucleus of the trigeminal,
      and the facial and external cuneate nuclei. The expression of genes encoding
      PTHrP and its receptor in discrete areas of the brain suggests that PTHrP may
      function as a neurotransmitter in the central nervous system.

PMID- 7723629
TI  - Tissue pH as an indicator of mRNA preservation in human post-mortem brain.
AB  - The relationship between pH and mRNA preservation in post-mortem human brain was
      examined using in situ hybridization histochemistry and Northern hybridization
      with oligonucleotide probes in a large group of human subjects, including control
      and neuropathological cases. Tissue pH was found to correlate strongly with
      preservation of four mRNA species in three brain areas. Tissue with low pH,
      assumed to result from prolonged terminal hypoxia, contained reduced or absent
      mRNA, while tissue with higher pH was found to contain quantifiable amounts, the
      values for pathological brain samples being comparable to those for control
      material of similar pH. Measurement of tissue pH provides a simple means to
      screen post-mortem brain for mRNA preservation and is suggested as a means to
      match material in case-control studies of human neurodegenerative disease.

PMID- 7723630
TI  - Beta APP mRNA transcription is increased in cultured fibroblasts from the
      familial Alzheimer's disease-1 family.
AB  - Familial (autosomal dominant) Alzheimer's disease (FAD) is a genetically
      heterogeneous disorder. Mutations in exons 16 and 17 of the amyloid beta-protein
      precursor (beta PP) gene currently account for less than 2% of FAD kindreds. No
      known defect in beta PP quantity, structure, or processing accounts for disease
      associated beta-amyloid deposition in the majority of early-onset FAD kindreds.
      Only two out of a sample of 48 pedigrees (particularly the early onset FAD 4
      kindred) contributed noticeably to evidence of linkage at the D21S16/13 and
      S1/S11 loci in the chromosomal region 21q21 [75]. Many early onset FAD pedigrees
      (including the FAD 1 and FAD 4 kindreds) show strong evidence of linkage to
      markers in the chromosome 14q24.3 region. Patients with trisomy 21 (Down's
      syndrome, DS) virtually always develop a histopathological phenotype
      indistinguishable from FAD, presumably on the basis of increased beta PP gene
      dosage and transcription. Whereas no beta PP gene duplication has been found in
      FAD, other mechanisms that augment beta PP production by effects at the
      transcriptional level could explain some FAD cases. Here, we report that cultured
      fibroblasts from affected members of the FAD 1 pedigree show a approximately 1.9
      fold increase (P = 0.007) in beta PP mRNA levels compared to unaffected members
      when the cells are grown under stressed conditions in 0.5% serum. The elevated
      levels of beta PP mRNA in cells cultured in 0.5% serum also cosegregate with
      haplotypes in the 14q24.3 region when analyzed by linkage methods (LOD score =
      3.26 at theta = 0.001). This is the chromosomal region to which FAD in this
      family has previously been mapped. As expected, fibroblasts from patients with DS
      used as a control show a similar beta PP mRNA increase. Fibroblasts from the FAD
      4 pedigree did not show this defect under the conditions utilized here. beta PP
      and A beta protein levels were determined quantitatively after metabolic labeling
      and immunoprecipitation and found to increase 2.0 and 2.5 fold, respectively, in
      the fibroblasts from affected FAD 1 members. Finally, transient transfections of
      a beta PP promoter/chloramphenicol acetyl transferase reporter gene construct
      demonstrated a approximately 3-4 fold increase in beta PP promoter activity in
      affected fibroblasts from the FAD 1 but not the FAD 4 pedigree. Taken together,
      these data raise the possibility that an increase in beta PP transcription may
      underlie the AD phenotype in at least some of the chromosome 14-linked FAD
      families.

PMID- 7723631
TI  - Exposure of neuronal cultures to K+ depolarization or to N-methyl-D-aspartate
      increases the transcription of genes encoding the alpha 1 and alpha 5 GABAA
      receptor subunits.
AB  - The transcription rates of the alpha 1, alpha 5, and alpha 6 gamma-aminobutyric
      acidA receptor subunit genes were analyzed in cultures maintained in low KCl
      (12.5 mM), in low KCl treated with NMDA (10 microM), and in high KCl (25 mM).
      alpha 1 and alpha 5 transcription rates were significantly increased in response
      to NMDA or high KCl treatment, while alpha 6 and cyclophilin transcription rates
      were not changed by either condition. These data suggest that following NMDA or
      high KCl treatment of granule cells, changes in alpha 1 and alpha 5 mRNA content
      are a consequence of a specific transcriptional rate increase of the
      corresponding subunit genes.

PMID- 7723632
TI  - Cloning and expression of a bovine glutamate transporter.
AB  - We have isolated a 3845 base-pair cDNA (BNGLUAS) encoding a bovine glutamate
      transporter (bovine GLAST) by screening a bovine retina cDNA library with an
      oligonucleotide probe corresponding to conserved regions of known glutamate
      transporters. The cDNA sequence predicted a protein of 542 amino acids and
      displayed 96% and 97% amino acid identity with the rat GLAST/GluT-1 and human
      GLAST, respectively. Expression of the bovine GLAST in Xenopus oocytes revealed
      Na(+)-dependent [14C]L-glutamate uptake and electrogenic glutamate uptake.

PMID- 7723633
TI  - Enhanced susceptibility of audiogenic seizures in Fyn-kinase deficient mice.
AB  - Mice with a mutation in fyn genes were examined for their susceptibility to
      acoustically primed audiogenic seizures. Homozygous mutant (fynz/fynz) mice were
      significantly more likely to have seizures and to show the stronger seizure
      syndrome (clonus). These results indicate that the susceptibility of acoustically
      primed audiogenic seizures is enhanced in the Fyn kinase deficient mice.

PMID- 7723634
TI  - The dual specificity phosphatase PAC-1 is transcriptionally induced in the rat
      brain following transient forebrain ischemia.
AB  - PAC-1 mRNA has previously been found only in activated T-cells in vitro and in
      vivo. The gene encodes a dual specificity protein phosphatase that regulates MAP
      kinase activity. Here, I describe that PAC-1 mRNA is induced also in neurons in
      the rat brain following 30 min of forebrain ischemia. At 6, 12 and 24 h after
      ischemia, PAC-1 mRNA was found most prominently in hippocampal cells which are
      resistant to 30 min of forebrain ischemia, but not in the selectively vulnerable
      CA1 sector. At later time points and in control animals no PAC-1 mRNA could be
      detected in any brain region. The protein-tyrosine/threonine phosphatase PAC-1,
      therefore, may be involved in adaptational responses of hippocampal cells
      resistant to ischemic injury.

PMID- 7723635
TI  - Determining the role of exercise in patients with chronic pulmonary disease.
AB  - Chronic pulmonary diseases are common in the community and their pathophysiology
      is complex. The principal symptoms are dyspnea and limited exercise capacity.
      Some, but not all, patients have true ventilatory limitation where the maximal
      exercise ventilation (VEmax) equals the measured maximal ventilatory volume
      (MVV). Those with obstructive disease have impeded expiration requiring an
      obligatory expiratory time for adequate lung emptying (i.e., a timing
      constraint). In these patients, increased breathing frequency during exercise
      tends to lead to hyperinflation and smaller tidal volumes, circumstances that
      predictably worsen breathing efficiency (i.e., result in high VD/VT). Those with
      restrictive disease characteristically have limited inspiratory capacity but
      unimpeded or even accelerated expiration (i.e. tidal volume constraint). These
      patients characteristically exhibit rapid respiratory rates (e.g., > 50.min-1) at
      end exercise.

PMID- 7723636
TI  - Coronary heart disease risk factors, physical activity, and fitness in young
      Danes.
AB  - In a random sample of young Danish adults (86 men and 115 women, 23-27 yr of age)
      maximal oxygen uptake (VO2max), physical activity (PA), blood pressure, blood
      lipids, body fat content, and smoking habits were studied. Cholesterol,
      triglyceride and body fat related negatively to VO2max. The ratio HDL/total
      cholesterol was positively related to VO2max (r = 0.3, P < 0.001), but no
      relationship was observed for HDL cholesterol. No association was found between
      PA and any of the risk factors. The relationships between different measures of
      PA and directly measured VO2max was around r = 0.3. No relationship existed
      between heart rate recorded during submaximal testing and PA (r = 0.0), which
      indicates that the method of assessing VO2max is important in demonstrating
      relationships to PA and risk factors. In conclusion, a favorable coronary heart
      disease risk profile was related to a higher VO2max, but not to time spent on
      physical activity. This suggests that in this age group intensity must be high
      enough to have an effect on VO2max before a preventive effect is present.

PMID- 7723637
TI  - Inverse relation of physical activity and apolipoprotein AI to blood pressure in
      elderly women.
AB  - To study the relation of habitual physical activity, diet, and serum lipoproteins
      to blood pressure, a cross-sectional study was carried out in a cohort of 202
      women, age 60-69 yr. Sitting, supine, and standing blood pressure was measured
      with a standard sphygmomanometer. Physical activity was assessed by
      questionnaire, diet by food records, serum lipoprotein cholesterol enzymatically,
      and apolipoprotein AI turbidimetrically. Among the women not taking
      antihypertensive medication (N = 127), the physically most active (physical
      activity 5 times per week or more) had sitting diastolic blood pressure of 86 mm
      Hg (adjusted for high-density-lipoprotein cholesterol, body mass index, and
      cardiovascular health status), which was 8 mm Hg lower (P = 0.007) than in the
      least active (physical activity twice per week or less) women. Subjects in the
      highest tertile of apolipoprotein AI (> 1.46 g.l-1) had a mean sitting systolic
      blood pressure of 147 mm Hg (adjusted for age, body mass index, and
      cardiovascular health status), which was 16 and 13 mm Hg lower (P = 0.001) than
      in women in the middle and lowest tertiles (< 1.32 g.l-1), respectively. The
      present data suggest that, in elderly women, regular physical activity is
      associated with a clinically significant lowering of diastolic blood pressure.
      Moreover, a higher level of serum apolipoprotein AI, the major protein component
      of high-density lipoprotein particles, is inversely associated with systolic
      blood pressure.

PMID- 7723638
TI  - Effect of recreational exercise on pregnancy weight gain and subcutaneous fat
      deposition.
AB  - This study was designed to test the hypothesis that continuing a regular regimen
      of recreational endurance exercise alters the time-specific rate of maternal
      weight gain and subcutaneous fat deposition during pregnancy. Serial measurements
      of body mass and 5-site skinfold thickness were obtained from 44 women before and
      during pregnancy who continued their preconceptional exercise regimen throughout
      pregnancy and from women who voluntarily stopped their preconceptional exercise
      regimen either before conception (N = 31) or reduced it below baseline fitness
      levels in very early pregnancy (N = 4). In the first and second trimester, the
      rate of weight gain and change in skinfold thicknesses were unrelated to exercise
      performance. However, those who continued exercise had a reduced rate of weight
      gain and change in skinfold thickness at specific sites in the last trimester of
      pregnancy. Overall weight gains were (mean +/- SEM) 13.0 +/- 0.5 kg and 16.3 +/-
      0.7 kg in the exercise and control groups, respectively, and the increases in the
      sum of skinfolds were 22 +/- 2 mm and 31 +/- 2 mm, respectively. We conclude that
      continuing a regular exercise regimen throughout pregnancy does not influence the
      rate of early pregnancy weight gain or subcutaneous fat deposition but decreases
      both in late pregnancy. However, overall pregnancy weight gain remains well
      within the normal range.

PMID- 7723639
TI  - Relationship of regional body composition to bone mineral density in college
      females.
AB  - The purpose of this study was to examine relationships between regional body
      composition and bone mineral density (BMD) in college females. Subjects were 12
      nonathletic females (< 3 h.wk-1 of exercise) and 46 female varsity athletes:
      basketball (N = 14), volleyball (N = 13), gymnastics (N = 13), and tennis (N =
      6). Dual energy x-ray absorptiometry was used to determine BMD and body
      composition. The mean (+/- SD) age, height, weight, and menarche for the subjects
      were 19.9 +/- 2.1 yr, 167.9 +/- 9.4 cm, 62.1 +/- 9.0 kg, and 13.6 +/- 1.7 yr,
      respectively. Mean lumbar (1.327 g.cm-2), femoral neck (1.172 g.cm-2), and total
      body (1.200 g.cm-2) BMD of the athletes were significantly greater than
      nonathletes (P < 0.05) but did not differ among the teams. Significant
      correlations were found between regional leg BMD and leg lean tissue mass (LTM)
      (r = 0.59, P < 0.001) and between arm LTM and arm and lumbar BMD (r = 0.47 and
      0.56, respectively). Significant correlations were also found between leg fat
      mass and leg BMD (r = 0.40). However, only regional LTM was a significant
      predictor of BMD using stepwise multiple regression. In summary, regional LTM
      appears to be a better predictor of BMD than regional fat mass.

PMID- 7723640
TI  - Sympathetic nerve activity to nonactive muscle of the exercising and
      nonexercising limb.
AB  - The purpose of this study was to determine whether efferent sympathetic nerve
      activity is different to resting skeletal muscles from the exercising and
      nonexercising limb. MSNA was measured by microneurography in both legs (peroneal
      nerve) in six subjects during 2 min of unilateral isometric knee extension (IKE;
      10-30% of maximum voluntary contraction (MVC)) followed by postexercise
      circulatory occlusion (PECO). Additional studies using isometric handgrip (30%
      MVC) followed by PECO were performed. IKE produced significant increases in mean
      arterial pressure (15 +/- 2 mm Hg) and heart rate (10 +/- 2 bpm). During PECO,
      mean arterial pressure remained significantly elevated (6 +/- 1 mm Hg) whereas
      heart rate returned to control. MSNA (bursts.min-1) was not different between the
      two limbs during control, IKE, PECO, and recovery. Seventy-five to eighty percent
      of all sympathetic nerve discharges occurred simultaneously in both legs, with
      the remaining percentage of sympathetic nerve discharges being divided almost
      equally between the nonexercising and exercising leg. Isometric handgrip produced
      significant increases in MSNA to the two resting legs with the percent of
      sympathetic discharges to the two legs being similar to that during IKE. These
      results indicate that MSNA is similar to the resting muscle in the exercising and
      nonexercising leg during brief, submaximal isometric exercise (< or = 30% MVC)
      and postexercise muscle ischemia.

PMID- 7723641
TI  - Effect of weight-training on energy expenditure and substrate utilization during
      sleep.
AB  - This study was performed to investigate the effect of weight-training (12 wk; 21
      male subjects) on energy expenditure and substrate utilization during sleep.
      Sleeping metabolic rate (SMR) as measured in a respiration chamber was calculated
      according to three procedures: the lowest mean energy expenditure of a shiftable
      3-h interval between 0:00 and 6:00 (SMR3) and SMR over predetermined intervals
      from 3:00 to 6:00 (SMR3-6) and from 0:00 to 6:00 (SMR0-6). In analogy with SMR
      the corresponding respiratory quotients were expressed as RQ3, RQ3-6, and RQ0-6.
      Changes in body composition were assessed from changes in body weight, body
      volume (densitometry), and total body water (deuterium dilution). Weight-training
      induced an increase in fat-free mass (+1.1 +/- 1.3 kg; P < 0.001) and a decrease
      in fat mass (-2.3 +/- 1.5 kg; P < 0.001) and body weight (-1.1 +/- 2.1 kg; P <
      0.05). There was no significant change in SMR, irrespective of the way SMR was
      expressed. Only RQ3 decreased significantly (from 0.82 +/- 0.04 to 0.79 +/- 0.02;
      P < 0.05). Remarkably RQ3, RQ3-6, and RQ0-6 were highly negative correlated with
      the pre-training RQ (r = -0.93, -0.91, and -0.90, respectively: P < 0.001)
      resulting in a diminished variation in post-training RQ (P < 0.001). These
      results suggest that weight-training has no effect on SMR but increases relative
      fat utilization in low fat oxidizers and vice versa for individuals displaying
      high pre-training lipid oxidation.

PMID- 7723642
TI  - CD4+/CD8+ T-lymphocyte ratio: effects of rehydration before exercise in
      dehydrated men.
AB  - Effects of fluid ingestion on CD4+/CD8+ T-lymphocyte cell ratios were measured in
      four dehydrated men (ages 30-46 yr) before and after 70 min of supine submaximal
      (71% VO2max) lower extremity cycle exercise. Just before exercise, Evans blue dye
      was injected for measurement of plasma volume. The subjects then drank one of six
      fluid formulations (12 ml.kg-1) in 3-4 min. All six mean posthydration (pre
      exercise) CD4+/CD8+ ratios (Becton-Dickinson Fluorescence Activated Cell Sorter
      and FACScan Consort-30 software program [San Jose, CA]) were below the normal
      range of 1.2-1.5; mean (+/- SE) and range were 0.77 +/- 0.12 and 0.39-1.15,
      respectively. The post-exercise ratios increased: mean = 1.36 +/- 0.15 (P < 0.05)
      and range = 0.98-1.98. Regression of mean CD4+/CD8+ ratios on mean plasma
      osmolality resulted in pre- and post-exercise correlation coefficients of -0.76
      (P < 0.10) and -0.92 (P < 0.01), respectively. The decreased pre-exercise ratios
      (after drinking) were probably not caused by the Evans blue dye but appeared to
      be associated more with the stress (osmotic) of dehydration. The increased post
      exercise ratios to normal levels accompanied the rehydration and were not due to
      the varied electrolyte and osmotic concentrations of the ingested fluids or to
      the varied vascular volume shifts during exercise. Thus, the level of subject
      hydration and plasma osmolality may be factors involved in the mechanism of
      immune system modulation induced by exercise.

PMID- 7723643
TI  - Fluid and carbohydrate ingestion independently improve performance during 1 h of
      intense exercise.
AB  - This study determined the effects of fluid and carbohydrate ingestion on
      performance, core temperature, and cardiovascular responses during intense
      exercise lasting 1 h. On four occasions, eight men cycled at 80 +/- 1% (+/- SEM)
      of VO2max for 50 min followed by a performance test. During exercise, they
      consumed either a large volume (1330 +/- 60 ml) of a 6% carbohydrate (79 +/- 4 g)
      solution or water or a small volume (200 +/- 10 ml) of a 40% maltodextrin (79 +/-
      4 g) solution or water. These trials were pooled so the effects of fluid
      replacement (Large FR vs Small FR) and carbohydrate ingestion (CHO vs NO CHO)
      could be determined. Performance times were 6.5% faster during Large FR than
      Small FR and 6.3% faster during CHO than NO CHO (P < 0.05). At 50 min, heart rate
      was 4 +/- 1 b.min-1 lower and esophageal temperature was 0.33 +/- 0.04 degrees C
      lower during Large FR than Small FR (P < 0.05) but no differences occurred
      between CHO and NO CHO. In summary, Large FR slightly attenuates the increase in
      heart rate and core temperature which occurs during Small FR. Both fluid and
      carbohydrate ingestion equally improve cycling performance and their effects are
      additive.

PMID- 7723644
TI  - Local cooling in wheelchair athletes during exercise-heat stress.
AB  - Wheelchair athletes with spinal cord injuries (WA) face challenges to thermal
      homeostasis, including reduced cutaneous vasoaction and sweat production. The
      purpose of this study was to evaluate the efficacy of local cooling to reduce
      heat strain in WA. Six elite, endurance-trained male WA (33 +/- 3 yr, 64 +/- 4
      kg) performed three strenuous exercise tests in a hot-humid environment (32.9 +/-
      0.1 degrees C, 75 +/- 3% RH) by pushing a racing chair on a stationary roller (30
      min, 16.5 km.h-1, 704-766 W metabolic heat) while wearing shorts and socks. The
      three treatments involved an ice-packet vest (V) (0.14 m2 of skin surface), a
      refrigerated headpiece (H) (0.16 m2), or no cooling (C) (control). The vest and
      headpiece offered potential cooling of 388 W and 266 W. Mean body heat storage
      for trials V (117 +/- 26 W), H (117 +/- 22 W), and C (164 +/- 40 W) were
      statistically similar, partly because V (117 +/- 47 W) and H (75 +/- 59 W) cooled
      inefficiently (30 and 28%, respectively). Repeated measure ANOVA indicated no
      significant between-treatment differences (P > 0.05) for any variable in trials
      V, H, and C. We concluded that local cooling during V and H was ineffective
      because heat storage decreased, but was not prevented.

PMID- 7723645
TI  - The relationship between cadence and lower extremity EMG in cyclists and
      noncyclists.
AB  - Male cyclists (N = 8) and noncyclists (N = 8) pedaled under six randomly ordered
      cadences (50, 65, 80, 95, 110 rpm and the preferred cadence) at 200 W to test the
      hypothesis that electromyographic activity of selected lower limb muscles is
      minimized at the preferred cadence. Average preferred cadences for cyclists (85.2
      +/- 9.2 rpm) and noncyclists (91.6 +/- 10.5 rpm) were not statistically
      different. Only gastrocnemius EMG was affected substantially and systematically
      by cadence changes, increasing linearly with cadence increases. Rectus femoris
      and vastus lateralis EMG displayed significant quadratic and linear relationships
      with cadence, respectively, but EMG differences between cadences were small for
      both muscles. Noncyclists did not exhibit significantly different patterns of
      muscle activity from cyclists, although there was a trend for soleus and
      gastrocnemius EMG to be higher in noncyclists. The results did not support our
      hypothesis that lower extremity muscle activation is minimized at an individual's
      preferred pedaling cadence. Thus, preferred cadence selection does not appear to
      be related to minimization of muscle activation. Given the nonlinear
      relationships between muscle mechanical properties, force, and EMG it is unlikely
      that a simple relationship exists between EMG and muscle stress.

PMID- 7723646
TI  - Incline, speed, and distance assessment during unconstrained walking.
AB  - Body accelerations during human walking were recorded by a portable measuring
      device. A new method for parameterizing body accelerations and finding the
      pattern of walking is outlined. Two neural networks were designed to recognize
      each pattern and estimate the speed and incline of walking. Six subjects
      performed treadmill walking followed by self-paced walking on an outdoor test
      circuit involving roads of various inclines. The neural networks were first
      "trained" by known patterns of treadmill walking. Then the inclines, the speeds,
      and the distance covered during overground walking (outdoor circuit) were
      estimated. The results show a good agreement between actual and predicted
      variables. The standard deviation of estimated incline was less than 2.6% and the
      maximum of the coefficient of variation of speed estimation is 6%. To the best of
      our knowledge, these results constitute the first assessment of speed, incline
      and distance covered during level and slope walking and offer investigators a new
      tool for assessing levels of outdoor physical activity.

PMID- 7723647
TI  - Lower and upper body anaerobic performance in male and female adolescent
      athletes.
AB  - Little data exist for upper and lower body mechanical power capability of
      adolescent athletes. This study compared arm (A) and leg (L) anaerobic peak and
      mean power (PP and MP) of 20 male and 20 female adolescent athletes after
      normalization for body mass (BM), fat-free mass (FFM), and lean A and L cross
      sectional area (CSA). Power outputs were assessed by the Wingate anaerobic test.
      FFM and CSA were estimated via anthropometry. No significant (P > 0.05)
      differences existed between the sexes in Tanner sexual maturity, chronological
      age, or overall training activity. Males had higher (P < 0.001) absolute PP (W)
      (L 694 vs 442; A 494 vs 309) and MP (L 548 vs 307; A 337 vs 214). Ratio
      normalization and ANCOVA were used to remove the influence of body size
      differences. Ratio normalization showed that males had greater leg PP/BM, MP/BM,
      MP/FFM, MP/CSA, as well as arm PP/BM and MP/BM, whereas all leg and arm PP and MP
      ANCOVA adjusted means for BM, FFM, and CSA, except arm MP adjusted for FFM, were
      significantly (P < 0.01) higher for males than females. We conclude that factors
      other than muscle mass, possibly qualitative in nature, are responsible for the
      sex difference in anaerobic performance of adolescent athletes.

PMID- 7723648
TI  - Physiological responses to in-line skating compared to treadmill running.
AB  - The physiologic responses to in-line skating were compared to those during
      treadmill running in 16 active males (18-37 yr). Each subject performed a VO2max
      test during in-line skating and treadmill running using speed-incremented,
      discontinuous protocols. Protocols were designed so that each subject completed 4
      6 stages. Stages were 3 min in duration and separated by a 5-min rest period. It
      was found that absolute VO2max (4.19 vs 4.44 l.min-1, P = 0.045), relative VO2max
      (56.8 vs 59.9 ml.kg-1.min-1, P = 0.054), and HRmax (189 vs 194 b.min-1, P < 0.05)
      were lower for in-line skating compared to treadmill running. Regression analyses
      were used to determine the submaximal relationship between modalities. There were
      no significant (P > 0.05) differences in the slope and y-intercept of the HR/VO2
      relationship, indicating a similar metabolic load at a given heart rate for both
      modes of exercise. Skating between 17.7-20.9 km.h-1 corresponded to 60-75% of
      VO2max or 75-90% of HRmax, which are common training intensities and within the
      guidelines recommended by the ACSM. Across the speeds investigated, caloric
      expenditure was 9.5-19.0 kcal.min-1. These results indicate that in-line skating
      elicits physiological responses comparable to treadmill running and thus would be
      another exercise alternative for improving aerobic capacity or maintaining body
      weight.

PMID- 7723649
TI  - VersaClimbing elicits higher VO2max than does treadmill running or rowing
      ergometry.
AB  - Collegiate varsity oarswomen and coxswain (N = 11) completed maximal aerobic
      exercise tests on a treadmill, a rowing ergometer, and a simulated climbing
      machine. Successful completion of each test was evidenced by a plateau in oxygen
      consumption in response to increasing work rates. VO2max (l.min-1), and minute
      ventilation (VE, l.min-1) at VO2max were significantly greater (P < 0.05) during
      simulated climbing compared to treadmill running and rowing ergometry. Maximal
      heart rate (beats.min-1) was significantly greater (P < 0.05) during climbing and
      running than during rowing. Findings indicate that progressive, incremental,
      whole-body climbing exercise elicits significantly greater VO2max values for
      collegiate oarswomen and coxswain than does graded treadmill running or
      progressive rowing ergometry.

PMID- 7723650
TI  - Accumulated oxygen deficit during supramaximal all-out and constant intensity
      exercise.
AB  - Two studies were conducted to test the validity of an all-out procedure for the
      assessment of the maximal accumulated oxygen deficit (AOD). Subjects in study 1
      (N = 9; VO2max = 57 +/- 3 ml.kg-1.min-1 [+/- SEM]) completed three supramaximal
      efforts on a cycle ergometer. Exhaustive exercise during an all-out isokinetic
      procedure (mean intensity of 149% VO2max) was compared with constant intensity
      exercise at approximately 110% and 125% VO2max. Subjects in study 2 (N = 12;
      VO2max = 55 +/- 3 ml.kg-1.min-1) completed a constant intensity test to
      exhaustion at approximately 110% VO2max and a 90 s all-out test on a Monark
      friction loaded cycle ergometer (mean intensity of 143% VO2max). The AOD within
      each study were not significantly different (study 1:43.9, 44.1, and 42.0 ml.kg-1
      for the 110%, 125%, and all-out tests; study 2: 52.1 and 51.2 ml.kg-1 for the
      110% and all-out tests, respectively; P > 0.05). The total amount of work was
      significantly greater the longer the test, the additional work being attributed
      to aerobic processes. The rate of both aerobic and anaerobic energy production in
      the first 30 s of exercise was directly related to exercise intensity and the
      protocol used. The results indicate that an all-out procedure provides a valid
      estimate of the maximal AOD and shows potential for a more complete assessment of
      anaerobic ability as traditional indices of high intensity exercise performance
      are also obtained.

PMID- 7723651
TI  - Age-related patterns in body composition for men aged 20-79 yr.
AB  - Fat-free body mass has been reported to decline by 30% between the ages of 30 and
      70 yr, whereas body weight increases until age 50 yr. This study examined the age
      related patterns in body composition, specifically its two components, fat-free
      body mass and fat mass, in 157 men aged 20-79 yr. Total body composition was
      assessed by hydrodensitometry and subcutaneous fat was measured with skinfolds.
      Approximately 15 men were tested in each of the 12 5-yr age groups (20-24, 25-29,
      30-34, ... 75-79 yr). Body density, as determined by underwater weighing, was
      lower successively from the youngest to oldest age groups; men below age 40 yr
      had significantly higher (P < 0.01) body densities than the older men. Although
      there was a gradual decline in fat-free body mass with increasing age, there was
      not a significant age group effect until age 70 yr. Fat mass gradually increased
      with increasing age; men above age 40 yr had significantly higher (P < 0.01)
      total body fat when compared to the younger men. Subcutaneous body fat was
      similar at the distal limb locations for each age group; however, the proximal
      trunk locations, especially the abdomen, demonstrated significantly (P < 0.01)
      higher skinfold thicknesses with increasing age. In conclusion, fat-free body
      mass was maintained to a later age than previously reported; thus, the age
      related decline in body density could be attributed to an age-related increase in
      body fat.

PMID- 7723652
TI  - Body fat and muscle thickness distributions in untrained young females.
AB  - Brightness-mode (B-mode) ultrasound was used to measure fat and muscle
      thicknesses on 44 untrained females (age = 18-29 yr, body density = 1.050 +/-
      0.009 (SD)g.ml-1, %fat = 21.5 +/- 4.1%) at eight sites (triceps, biceps, forearm,
      subscapular, abdomen, quadriceps, hamstrings, and posterior calf). The
      correlation coefficients between fat and muscle thickness were not significant at
      any measurement site except for the triceps (r = -0.32, P < 0.05).
      Intercorrelation analyses among the eight sites were significant (P < 0.05) in
      almost all cases for fat thickness, while mainly between adjoining sites for
      muscle thickness. However, both tissues had a low degree of generality in
      thickness among sites. Fat thickness at all measurement sites was significantly
      correlated with body density except for the posterior calf; the best correlation
      was found with the quadriceps (r = -0.73). On the other hand, for muscle
      thickness, only the forearm and triceps were significantly correlated with body
      density. These results show 1) the extent of muscled and fat thicknesses are
      independent each of other within the same region, 2) fat and muscle thicknesses
      have a high degree of specificity in site distribution, and 3) fat thickness
      measurements determined from B-mode ultrasound may be of significant value
      assessing total body composition.

PMID- 7723653
TI  - Determining the optimal mix of exercise activities using mathematical
      programming.
AB  - Several mathematical programming models designed to develop optimal exercise
      programs are described. The models can be adapted to various individuals so that
      unique objectives and constraints can be met. The models can be used to design
      individualized exercise programs for a wide variety of people. Models can meet
      the needs of those who exercise for recreational purposes, athletic achievements
      and/or rehabilitative purposes. As the objectives of an exercise program and the
      constraints on it change over time, individuals must occasionally review the
      relevancy of the objective function and constraints. The model must then be
      updated so that the updated optimal exercise program can be designed. An
      illustrative example that deals with the development of an overall fitness
      program for individuals exercising for recreational reasons is described.

PMID- 7723654
TI  - Effect of slope variation and skating technique on velocity in cross-country
      skiing.
AB  - The purpose of the present study was to investigate the effect of slope
      variations upon the maximal velocity attainable by cross-country ski racers using
      three skating techniques (V-1, V-2, and Gunde). Nine (2 females, 7 males) junior
      ski racers (16.0 +/- 0.4 yr of age, mean +/- SEM) exhibiting strong technical
      skills participated in the study. The subjects were required to skate at maximal
      velocity over five different courses (length 120-200 m) with mean slopes of -1,
      0, 6, 9, and 12%. Video analysis was used to determine skiing velocity, cycle
      length, and cycle rate. Heart rate was monitored to verify intensity of exertion.
      Results indicated that intensities were similar to those observed while racing.
      Velocities for the three techniques were not different for -1, 0, and 6% slopes.
      However V-1 was significantly faster (P < 0.01) at 9% and 12% inclines. Velocity
      was highly correlated to cycle length (P < 0.01) but unrelated to cycle rate.
      Cycle length was significantly different between techniques (P < 0.01) and varied
      across slopes. Cycle rate was significantly different between techniques (P <
      0.01) but did not vary across slopes. Thus, our results indicate that any of the
      three techniques is adequate on flat and rolling terrain, but V-1 should be used
      at slopes of 9% and above. It is also concluded that during short trials skied at
      maximal velocity, skiing velocity is highly dependent on cycle length and
      independent of cycle rate.

PMID- 7723655
TI  - The effect of trial size and variability on statistical power.
AB  - A computer model was developed, validated, and used in conjunction with Monte
      Carlo procedures to study the effects of sample size (subjects and trials), mean
      differences, and subject variability on statistical power. Also examined were the
      differences between single subject (SS) and group results. Mean differences were
      varied from 1/4 to 4 times the distribution SD resulting in improved power
      values. Mean group F results ranged from 63.6% to 100% while SS results were
      poorer, especially for the smaller mean differences (16.8%-100%). Subject
      variability was examined for a Simple model and two Complex (MOD1 and MOD4)
      models. MOD1 produced group results similar to the corresponding Simple model
      with an overall mean of 78.2% and a Complex/Simple (C/S) ratio of 0.99. The more
      variable model (MOD4) produced fewer significant results (52.9%) and a lesser C/S
      ratio (0.82). The SS results were more dramatic. The percentages of significant
      values were less (38.1% and 33.9%) and the C/S ratios favored the Complex models
      (1.48 and 3.17). Both sample size and trial size had a major impact on the
      results. In summary, these results provide additional insight into the
      interactive effects and importance of the factors investigated, especially in the
      area of SS experiments.

PMID- 7723656
TI  - Astroglial reactivity in natural scrapie of sheep.
AB  - Astrogliosis is known to be a common histological feature in experimental
      scrapie, but astroglial reactivity in natural scrapie of sheep has not yet been
      precisely studied. We investigated the expression of two markers of glial
      plasticity, glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS),
      by Western and Northern blotting, in different areas of the sheep brain. We
      report that both GFAP-mRNA and GFAP are overexpressed in the cerebellum and the
      pons. In the thalamus, overexpression of GS was demonstrated for the first time
      in this disease. The enhancement of this astroglial metabolic marker, essential
      for glutamate and ammonia neutralization, cellular function and brain
      detoxification, could represent an attempt by astrocytes to maintain and control
      the cerebral homeostasis in this area. Our results show that astrocytes: (i) are
      a target for the scrapie agent even in the early temporal evolution of the
      disease; (ii) react by overexpressing their intermediate filament major protein,
      changing their phenotypic appearance and stabilizing their processes in precise
      brain areas; (iii) overexpress key elements of their metabolism. These changes
      clearly implicate astrocytes in the pathogenesis of the disease.

PMID- 7723657
TI  - Role of leuX in Escherichia coli colonization of the streptomycin-treated mouse
      large intestine.
AB  - Escherichia coli F-18, a normal human fecal isolate, is an excellent colonizer of
      the streptomycin-treated mouse large intestine. E. coli F-18 Col-, a derivative
      of E. coli F-18 that no longer makes the E. coli F-18 colicin, colonizes the
      mouse large intestine as well as E. coli F-18 when fed alone, but is eliminated
      when fed together with E. coli F-18. Recently, a random bank of E. coli F-18 DNA
      was transformed into E. coli F-18 Col-, the resultant population was fed to
      streptomycin-treated mice, and the intestine was used to select the best
      colonizer. In this fashion, a 6.5 kb E. coli F-18 DNA fragment was isolated. This
      fragment was shown to enhance E. coli F-18 Col- mouse large intestinal colonizing
      ability and survival during stationary phase in intestinal mucus in vitro, as
      well as stimulate the synthesis of type-1 fimbriae. Here, we present evidence
      that the gene responsible for the enhanced E. coli F-18 Col- colonizing ability
      and survival during stationary phase in vitro is leuX. This gene encodes a rare
      leucine tRNA specific for the UUG codon. In addition, we show that the presence
      of a functional leuX gene is necessary for E. coli K-12 intestinal colonization
      and for survival in stationary phase.

PMID- 7723658
TI  - Immune response against the L-lactate dehydrogenase of Mycoplasma hyopneumoniae
      in enzootic pneumonia of swine.
AB  - The L-lactate dehydrogenase (LDH) of Mycoplasma hyopneumoniae, formerly named
      protein P36, belongs to the predominant immunogenic proteins in pigs which were
      naturally or experimentally infected with M. hyopneumoniae. The antigenic
      reaction against M. hyopneumoniae LDH has been shown to be species specific.
      Recombinant M. hyopneumoniae LDH, which was genetically engineered to contain six
      histidine residues at its C-terminal end, was expressed in E. coli and purified
      to a high degree using Ni-chelate affinity chromatography. The genetically
      engineered LDH still showed the same biochemical activity and immunological
      specificity as the wild-type LDH and was used as an antigen for a M.
      hyopneumoniae LDH ELISA. Using this assay, we showed that pigs experimentally
      infected with M. hyopneumoniae raised antibodies against LDH in two steps. An
      early, relatively weak anti-LDH response was detected between 5 to 10 weeks post
      infection when clinical signs and lung lesions occur. This first minor raise of
      anti-LDH antibodies occurred simultaneously with the strong appearance of
      antibodies against an antigen consisting of membrane proteins of M. hyopneumoniae
      prepared with Tween 20 extraction. A second, strong raise in anti-LDH antibodies
      was observed from the twelfth week after infection, at a time when the disease
      signs and the infectious agent disappeared. The high anti-LDH titer persisted
      until 21 weeks post-infection, in contrast to the antibody titer against the
      membrane proteins which started to decrease after its peak at 12 weeks post
      infection. A LDH-ELISA may also be useful for detecting past infections.

PMID- 7723660
TI  - Expression and mutagenesis of recombinant cholera toxin A subunit.
AB  - ADP-ribosylating protein exotoxins from Vibrio cholerae (CT) and Escherichia coli
      (LT-I) share two short regions of sequence similarity with Bordetella pertussis
      toxin (PT). Previous studies have indicated that substitution of arginine for
      lysine 7 within the first region of CT drastically decreases ADP
      ribosyltransferase activity. We have more closely defined the role of other amino
      acids in this region by generating modified proteins in which arginine 7 was
      replaced with lysine (R7K), aspartate 9 was replaced with arginine (D9R), glycine
      was substituted for proline 12 (P12G), amino acids 6 to 13 were deleted (delta
      613) or the C-terminal KDEL sequence was changed to NEDL. The modified proteins
      R7K, D9R and delta 613 exhibited undetectable ADP ribosyltransferase activity.
      Comparison of the tryptic digest of R7K with native CT suggested that changes in
      protein conformation may be responsible for the loss of ADP-ribosylation
      activity.

PMID- 7723659
TI  - Localization of protection-eliciting epitopes on PspA of Streptococcus pneumoniae
      between amino acid residues 192 and 260.
AB  - Pneumococcal surface protein A (PspA) is a virulence factor of Streptococcus
      pneumoniae that can elicit a protective antibody response. The pspA gene of
      strain Rx1 encodes a 65 kDa molecule composed of 588 amino acids. The N-terminal
      288 amino acids are highly charged, and predict an alpha-helical coiled-coil
      protein structure. All monoclonal antibodies (MAbs) to PspA, obtained by
      screening against whole pneumococci, bind to the alpha-helical region of PspA,
      suggesting that this region is surface exposed. The C-terminal 217 amino acids of
      PspA contain the surface anchor of PspA and does not appear to be alpha-helical.
      In the middle of the molecule is a proline-rich region that is thought to
      traverse the cell wall. In this study we have mapped the immunogenic epitopes
      detected by 9 MAbs that were made against strain Rx1 PspA. Five of the MAb also
      react with the PspA of mouse virulent strain WU2. All epitopes were found in one
      of two portions of the alpha-helical region. One comprised the first 115 amino
      acids, and the other was within amino acids 192 and 260. The five MAbs that
      recognize WU2 PspA, but not the remaining four MAbs, were protective against
      strain WU2. The epitopes detected by four of the five protective MAbs mapped to
      region 192 to 260 of Rx1 PspA. The existence of protective epitopes in this
      region was confirmed by demonstrating that mice immunized with the cloned
      fragment containing these residues were protected from fatal infection with WU2.
      Since amino acids 192 to 260 are in the region of PspA anticipated to be adjacent
      to the cell wall, and probably well covered by capsule, the means by which
      antibodies to the region lead to protection is not obvious.

PMID- 7723661
TI  - Multiple anti-cytokine activities secreted from tanapox virus-infected cells.
AB  - Tanapox virus (TPV) produces a mild disease in humans characterized by transient
      fever, one or more nodular skin lesions and regional lymphadenopathy. We
      demonstrate that TPV-infected cells, but not mock-infected cells, secrete an
      early 38 kDa glycopeptide that, unlike any other known protein, binds to human
      (h) interferon-gamma, hIL-2 and hIL-5. In concomitant experiments this
      polypeptide failed to bind to hIL-1 alpha, hIL-3, hIL-4, hIL-6, hIL-7, hIL-8 or
      hIL-10. Inhibition of hIL-2 and hIL-5 biological activities were demonstrated
      using a hIL-2-dependent mouse T cell line (HT-2) and a hIL-5-dependent
      erythroleukemia cell line (TF-1), respectively. The 38 kDa polypeptide also
      inhibited the bioactivity of interferon-gamma. Taken together, our results
      suggest that TPV has evolved multiple pathways to disarm both TH1 cell-mediated
      (IL-2 and interferon-gamma) and TH2-associated (IL-5) immune responses for its
      infectivity with remarkable genetic economy.

PMID- 7723662
TI  - Identification of a molecule of Porphyromonas gingivalis that binds to
      Streptococcus gordonii.
AB  - The molecules that mediate the adherence of Porphyromonas gingivalis, a
      periodontal pathogen, to Streptococcus gordonii, a commensal plaque organism,
      were investigated. Outer membrane proteins of P. gingivalis were labelled with
      biotin, extracted by EDTA and reacted with S. gordonii cells. Interactive
      porphyromonas components were identified by SDS-PAGE of the S. gordonii cells
      followed by electroblotting and visualization of the adsorbed porphyromonas
      molecules with streptavidin-alkaline phosphatase. A P. gingivalis molecule of 35
      kDa bound to S. gordonii. Monospecific polyclonal antibodies to the 35 kDa
      protein inhibited binding of P. gingivalis to S. gordonii by 71%. The antibodies
      also reacted with the P. gingivalis fimbriae, indicating that the 35 kDa molecule
      is antigenically related to, or associated with, the fimbriae.

PMID- 7723663
TI  - Effect of testosterone on bone density and bone metabolism in adolescent male
      hypogonadism.
AB  - To assess the influence of gonadal steroid testosterone (T) on bone mineral
      status in males during puberty, we observed the response of cortical bone density
      and serum biochemical parameters of bone metabolism to T treatment in 12
      adolescent patients with hypogonadotropic hypogonadism (11 with both gonadotropin
      and growth hormone deficiency and one with isolated gonadotropin deficiency). The
      12 patients aged 15 to 21 years (Tanner stage I to II) were divided into two
      groups: group 1 (n = 6) given T treatment for 2 consecutive years, and group 2 (n
      = 6) without T treatment for the first year and then with T treatment for the
      second year. Cortical bone density measured in the radius was less than the age
      matched mean value for normal subjects in all 12 patients (groups 1 and 2) at the
      start of the study. Bone density in group 1 increased significantly during the 2
      year T treatment period, but did not increase in group 2 during the first year
      without T treatment, although an increase was observed during the subsequent year
      with T treatment. Among circulating biochemical factors such as osteocalcin,
      parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), and 1,25
      dihydroxyvitamin D [1,25-(OH)2D], only osteocalcin showed an increase in response
      to T treatment in both groups. Levels of insulin-like growth factor-I (IGF-I)
      remained consistently low and did not change in any patients except one with
      isolated gonadotropin deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723664
TI  - Overnight branched-chain amino acid infusion causes sustained suppression of
      muscle proteolysis.
AB  - Short-term (3 to 4 hours) infusion of branched-chain amino acids (BCAA) has been
      shown to suppress muscle protein breakdown. Whether these effects are sustained
      with chronic elevations of BCAA is not known. In the present study, we examined
      the effect of an overnight (16-hour) systemic BCAA infusion on whole-body and
      skeletal muscle amino acid metabolism, as assessed by simultaneously measured 3H
      phenylalanine and 14C-leucine kinetics in eight normal volunteers; 10 overnight
      fasted subjects studied during a 4-hour saline infusion served as controls.
      Overnight BCAA infusion increased plasma BCAA concentrations by fivefold to
      eightfold, and this was associated with a 20% to 60% decline in arterial
      concentrations of other amino acids. For Phe, this decline was mediated by a
      reduction in the systemic rate of appearance ([Ra] 0.38 +/- 0.03 v 0.60 +/- 0.01
      mumol/kg/min for BCAA and saline, respectively, P < .001). Endogenous Leu Ra,
      calculated more indirectly as the difference between the total Leu Ra and the
      unlabeled Leu infusion rate, did not differ between groups. In the forearm,
      overnight BCAA infusion resulted in a diminished net release of Phe (-3 +/- 2 v 
      18 +/- 4 [saline] nmol/min/100 mL, P < .02), and BCAA balance became markedly
      positive (751 +/- 93 v -75 +/- 30, P < .001). The diminished net forearm Phe
      release was accounted for by a decrease in local Phe Ra (P < .02). As with the
      systemic endogenous Leu Ra, forearm Leu Ra was not reproducibly affected by
      infused BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723665
TI  - Effects of weight loss on norepinephrine and insulin levels in obese older men.
AB  - Older individuals have higher plasma insulin and norepinephrine (NE) levels than
      the young. This may be due to biological aging; however, these changes also may
      be due in part to the increase in abdominal obesity that often accompanies aging.
      The latter possibility was tested by examining the effects of weight loss on
      plasma insulin and NE levels in 11 healthy men aged 52 to 72 years who had mild
      to moderate obesity (body mass index [BMI], 27 to 36 kg/m2). Plasma insulin
      levels were measured during an oral glucose tolerance test, and on a second day
      NE levels were measured during supine rest and upright posture. Subjects lost 10
      +/- 5 kg (mean +/- SD) and decreased their waist to hip ratio ([WHR] an index of
      the pattern of regional fat distribution) 2.8% (P < .01) over 9 +/- 3 months
      through mild caloric restriction. This resulted in a 23% decrease (P < .05) in
      fasting insulin levels and a 48% decrease (P < .01) in 2-hour insulin levels.
      Weight loss also resulted in a 31% decrease (P < .001) in supine plasma NE levels
      and an 8% decrease (P < .05) in supine diastolic blood pressure (BP). Decreases
      in supine plasma NE levels correlated with changes in WHR (r = .61, P < .05), but
      did not correlate with changes in other measures of body composition or with
      changes in glucose and insulin levels. These results suggest that higher plasma
      NE levels are related to the distribution of body fat to upper-body or abdominal
      sites in obese older men.

PMID- 7723666
TI  - Effects of nandrolone propionate on experimental tumor growth and cancer
      cachexia.
AB  - We studied the tumor host response to excessive doses of an anabolic steroid
      (nandrolone propionate, 2.5 mg 20 g intraperitoneally every second day for 11
      days) with respect to body composition and tumor cell kinetics in MCG 101 sarcoma
      bearing mice (C57BL/6J) with progressive cachexia. Although survival and food
      intake were not affected, a significant weight gain was observed that was
      essentially attributed to water retention. Net protein content was increased only
      to a minor extent (15%), of which only the liver accounted for a significant part
      of the body compartments. Hepatic protein accumulation was obviously caused by
      decreased protein degradation, since hepatic RNA content was unchanged. After
      anabolic steroid administration, reduced histochemical staining of succinate
      dehydrogenase was observed in skeletal muscles rich in oxidative type 1 fibers,
      but it was not different from that of tumor-bearing control animals, which was
      also confirmed by measurements of citrate synthase and cytochrome c oxidase
      activities in skeletal muscle and liver tissue. The anabolic steroid had no
      significant effect on tumor growth in terms of weight progression, energy state,
      polyamine synthesis rate, cell division rate, and cell cycle cytocompartments. We
      conclude that anabolic steroid supplementation is not therapeutically beneficial
      in counteracting progressive weight loss in experimental cancer.

PMID- 7723667
TI  - Compartmental modeling of glucagon kinetics in the conscious dog.
AB  - The aim of the present study was to examine glucagon metabolism and distribution
      using both compartmental-modeling approaches and steady-state organ-balance
      techniques in conscious, overnight-fasted dogs. Arterial plasma glucose
      concentrations were clamped at 14 mmol/L with a variable exogenous glucose
      infusion. Somatostatin was infused to block endogenous secretion of insulin and
      glucagon. Insulin was replaced intraportally at 2.4 pmol.kg-1.min-1 to maintain
      basal insulin concentrations in the range from 70 +/- 4 to 95 +/- 12 pmol/L.
      Glucagon was not given during the control period, but was subsequently infused
      peripherally in four 1-hour steps of 1.0, 3.0, 6.0, and 3.0 ng.kg-1.min-1.
      Glucagon levels increased from 0 to 68 +/- 6, 195 +/- 19, 378 +/- 47, and 181 +/-
      20 ng/mL. Compartmental analysis of glucagon concentrations showed that glucagon
      was distributed in one compartment with a volume approximately equal to the
      plasma volume. The metabolic clearance rate of glucagon was 17.6 mL.kg-1.min-1.
      The liver cleared 24% of glucagon, and the kidneys, 17%.

PMID- 7723668
TI  - Coexisting type III hyperlipoproteinemia and familial hypercholesterolemia: a
      case report.
AB  - A 39-year-old man presented with type III hyperlipoproteinemia in association
      with heterozygous familial hypercholesterolemia (FH). He had extensive tuberous
      xanthomas over the knees and elbows and xanthomas in the Achilles tendons. He
      also had palmar xanthomas. He exhibited severe hypercholesterolemia and
      hypertriglyceridemia. This patient was heterozygous for FH, as evidenced by low
      low-density lipoprotein (LDL) receptor function on lymphocytes, and had type III
      hyperlipoproteinemia, as determined by apolipoprotein (apo) E phenotype 2/2 in
      isoelectric focusing of the E isoproteins and the presence of a broad beta band
      on electrophoresis. Because therapy consisting of diet restrictions and lipid
      lowering agents such as clinofibrate and niceritrol did not decrease serum total
      cholesterol ([TC] 15.26 mmol/L) and triglyceride ([TG] 10.79 mmol/L) levels
      effectively, the patient underwent plasmapheresis once every 2 weeks using a
      dextran sulfate-cellulose column. Repeated plasmapheresis markedly reduced serum
      TC and TG and induced complete regression of the palmar xanthoma after 6 months.
      The severity of tuberous xanthomas on the knees and elbows was reduced after 2.5
      years. After plasmapheresis, TC decreased to 1.94 mmol/L from 10.40 mmol/L and TG
      decreased to 0.33 mmol/L from 7.90 mmol/L. Plasmapheresis performed with a
      dextran sulfate-cellulose column was highly effective in removing the lipoprotein
      remnant particles in this patient, leading to generalized improvement in the
      lipoprotein profile.

PMID- 7723669
TI  - Isotopic evidence for the differential regulation of arginine and proline
      synthesis in man.
AB  - Arginine and proline derive from the metabolism of delta 1-pyrolline-5
      carboxylate, a product of intestinal glutamic acid metabolism. We studied the
      extent of glutamate, arginine, and proline synthesis in four adult fed and fasted
      women. The subjects ingested a single dose of a mixture of uniformly (U)-13C
      labeled amino acids and carbohydrate of algal origin. Frequent blood samples were
      taken for 24 hours. All the mass isotopomers of plasma lysine, glutamate +
      glutamine (GLX), arginine, and proline were measured using negative chemical
      ionization, selected-ion monitoring gas chromatography-mass spectrometry. In this
      isotopic approach, the appearance of U-13C-amino acid in the plasma reflects
      entry of the dietary amino acids, and the appearance of 13C in lower mass
      isotopomers demonstrates synthesis of the respective amino acids by the subject.
      All the mass isotopomers (including [M + 4]) of GLX became enriched with 13C. We
      suggest that the [M + 4] isotopomer of GLX reflects synthesis of the amino acid
      from alpha-ketoglutarate derived from the metabolism of U-13C-carbohydrate by the
      bacterial flora. Arginine labeling showed two patterns. The [M + 5] isotopomer of
      plasma arginine was labeled as rapidly as [M + 6] (ie, tracer) arginine, and we
      propose that the appearance of the [M + 5] isotopomer reflects the synthesis of
      citrulline from dietary [M + 5]-glutamate in first pass. The [M + 1] to [M + 3]
      isotopomers of arginine were also labeled for a prolonged period of time,
      suggesting that systemic glutamate was also a precursor for arginine
      synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723670
TI  - Fasting plasma insulin level is an important risk factor for the development of
      complications in Japanese obese children--results from a cross-sectional and a
      longitudinal study.
AB  - It is not known what types of factors may contribute to the development of
      complications in obese children. In the current investigation, we have performed
      a cross-sectional and a longitudinal study in Japanese obese children to clarify
      the relationship of the extent of obesity, fat distribution, insulin resistance,
      and aging to the development of obesity-related complications. In the cross
      sectional study of 329 obese boys and 142 obese girls aged 7 to 15 years, the
      fasting plasma immunoreactive insulin (IRI) level was significantly higher than
      that of 46 non-obese boys and 48 non-obese girls (boys, 13.4 +/- 6.7 v 4.9 +/-
      1.9 microU/mL, P < .001; girls, 14.0 +/- 5.9 v 4.8 +/- 1.8, P < .001). Linear
      regression analysis demonstrated that fasting plasma IRI correlated positively
      with fasting plasma glucose (FPG), triglycerides (TG), uric acid (UA), and
      systolic blood pressure (SBP) in obese boys, and with TG, SBP, and diastolic
      blood pressure (DBP) in obese girls, and negatively with serum high-density
      lipoprotein cholesterol (HDL-C) in both obese boys and girls. Multiple regression
      analysis demonstrated that fasting plasma IRI was independently and positively
      correlated with FPG, TG, and SBP in obese boys. Fasting plasma IRI in obese girls
      was positively correlated with TG, SBP, and DBP, and negatively with HDL-C. FPG
      decreased significantly in non-obese children at the onset of puberty, but it
      remained unchanged in obese children. Fasting plasma IRI and the IRI to glucose
      ratio increased with age in obese children, whereas they did not show any
      significant changes in non-obese children.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723671
TI  - Suppression of hepatic gluconeogenesis in long-term Troglitazone treated diabetic
      KK and C57BL/KsJ-db/db mice.
AB  - The orally effective antidiabetic agent Troglitazone (CS-045) exerts hypoglycemic
      effects in various insulin-resistant obese and/or diabetic animals. Since
      increased hepatic gluconeogenesis is a major cause of hyperglycemia in these
      diabetic animals, we evaluated the effect of long-term Troglitazone treatment on
      hepatic gluconeogenesis. Troglitazone was administered for 7 days to normal ddY
      mice, diabetic KK mice, diabetic C57BL/KsJ-db/db mice, and its heterozygote, db/+
      mice, as a 0.1% or 0.2% food admixture. Troglitazone significantly decreased
      plasma glucose in diabetic KK and db/db mice, but not in normal ddY and db/+
      mice. 14C incorporation into blood glucose from NaH14CO3 was measured to assess
      hepatic gluconeogenesis in diabetic KK and normal ddY mice. Hepatic
      gluconeogenesis was significantly increased in diabetic KK mice (P < .01) as
      compared with normal mice, and was significantly suppressed (P < .05) after 7
      days of Troglitazone treatment (approximately 200 mg/kg/d). Glucose-6-phosphate
      (G6P) and fructose-6-phosphate (F6P) were significantly decreased but fructose
      1,6-bisphosphate (FBP) was not significantly increased in the liver of diabetic
      db/db mice treated with Troglitazone for 7 days (approximately 80 mg/kg/d) as
      compared with control db/db mice. These changes in G6P, F6P, and FBP corresponded
      with the activity of fructose-1,6-bisphosphatase (Fru-1,6P2ase) and 6
      phosphofructo-1-kinase (6-PF-1K), which determined the content of F6P and FBP.
      Namely, Fru-1,6P2ase was significantly decreased in Troglitazone-treated db/db
      mice as compared with control mice, whereas 6-PF-1K activity was not affected by
      Troglitazone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723673
TI  - Fatty acid oxidation and cardiac function in the sodium pivalate model of
      secondary carnitine deficiency.
AB  - Carnitine-deficiency syndromes are often associated with alterations in lipid
      metabolism and cardiac function. The present study was designed to determine
      whether this is also seen in an experimental model of carnitine deficiency.
      Carnitine deficiency was induced in male Sprague-Dawley rats supplemented with
      sodium pivalate for 26 to 28 weeks. This treatment resulted in nearly a 60%
      depletion of myocardial total carnitine content as compared with control hearts.
      When isolated working hearts from these animals were perfused with 5.5 mmol/L
      glucose and 1.2 mmol/L palmitate and subjected to incremental increases in left
      atrial filling pressures, cardiac function remained dramatically depressed. The
      effects of carnitine deficiency on glucose and palmitate utilization were also
      assessed in hearts perfused at increased workload conditions. At this workload,
      function was depressed in carnitine-deficient hearts, as were rates of 1.2-mmol/L
      [U-14C]-palmitate oxidation, when compared with control hearts (544 +/- 37 vs 882
      +/- 87 nmol/g dry weight.min, P < .05). However, glucose oxidation rates from 5.5
      mmol/L [U-14C]-glucose were slightly increased in carnitine-deficient hearts. To
      determine whether the depressed fatty acid oxidation rates were a result of
      reduced mechanical function in carnitine-deficient hearts, the workload of hearts
      was reduced. Under these conditions, mechanical function was similar among
      control and carnitine-deficient hearts. Palmitate oxidation rates were also
      similar in these hearts (526 +/- 69 v 404 +/- 47 nmol/g dry weight.min for
      control and carnitine-deficient hearts, respectively).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7723672
TI  - Does lipoprotein or hepatic lipase activity explain the protective lipoprotein
      profile of premenopausal women?
AB  - Numerous studies have reported that women have a lipoprotein profile suggestive
      of a reduced risk of coronary heart disease (CHD). We have therefore tested
      whether the "protective" lipoprotein profile of women could be explained by
      differences in hepatic lipase (HL) or lipoprotein lipase (LPL) activities. In the
      present study, 14 non-obese healthy premenopausal women had higher plasma
      concentrations of high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C,
      and HDL-apolipoprotein (apo) AI, and a higher ratio of HDL-C to low-density
      lipoprotein cholesterol (LDL-C) than 17 non-obese healthy men. Women also had
      lower plasma triglyceride (TG), HDL-TG, and apo B levels than men. Plasma
      postheparin LPL (PH-LPL) and HL activities showed no significant sex dimorphism,
      whereas abdominal and femoral adipose tissue (AT)-LPL activities were
      significantly higher in women (P < .005). In men, PH-LPL activity correlated
      significantly with plasma HDL2-C (r = .52, P < .05), LDL-C (r = -.47, P < .05),
      and apo B (r = -.56, P < .01) levels, as well as with the HDL-C/LDL-C ratio (r =
      .67, P < .005). No such relationships were found in women, with the exception of
      HL activity, which was negatively correlated with HDL-apo AI levels. In both
      genders, abdominal AT-LPL activity showed no significant association with plasma
      lipoprotein levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723674
TI  - Insulin binding in non-insulin-dependent diabetes mellitus (NIDDM) is correlated
      with glycemic control: clinical evidence for abnormal receptor regulation in
      NIDDM.
AB  - Insulin binding has been reported to be decreased in non-insulin-dependent
      diabetes mellitus (NIDDM). Although elevated basal insulin concentrations have
      been correlated with decreased insulin binding in obesity, this relationship has
      not been found in NIDDM. To determine the potential cause(s) of the decrease, we
      measured 125I-insulin binding to circulating monocytes isolated from 31 non
      insulin-treated patients with NIDDM who had a fasting plasma glucose (FPG)
      concentration greater than 7.8 mmol/L and 13 control subjects. We examined the
      influence of obesity, insulin concentration, glycemic control, and treatment with
      oral hypoglycemic agents on insulin binding in a cross-sectional study. Insulin
      binding was significantly decreased in the entire NIDDM group (mean +/- SEM,
      %/10(7) monocytes: 4.65 +/- 0.33) as compared with controls (6.45 +/- .70, P <
      .02). Subgroups defined by obesity (relative body weight > 1.2) and poor glycemic
      control (FPG > 11.1 mmol/L) and those not taking oral hypoglycemic agents had
      significantly lower insulin binding (P < .02). However, neither relative body
      weight nor insulin concentrations (basal or stimulated) correlated with insulin
      binding. Stepwise linear regression analysis showed that only FPG significantly
      correlated with insulin binding (r = -.45, P = .002) even when oral hypoglycemic
      agent-treated patients were removed from the analysis (r = -.50, P = .003). There
      was no significant contribution to explain insulin binding by the other
      variables, including diagnosis of diabetes, obesity, insulin concentration, or
      treatment with oral hypoglycemic agents. We conclude that poor metabolic control
      is associated with an alteration in insulin receptor regulation in NIDDM.

PMID- 7723675
TI  - Reduced testosterone and adrenal C19 steroid levels in obese men.
AB  - It has been reported that a high proportion of abdominal fat is associated with
      increased plasma androgen concentrations in women. Although less evidence is
      available, abdominal obesity appears to be associated with low plasma
      testosterone (T) levels in men. We have therefore examined in 80 men (aged 36.3
      +/- 3.2 years, mean +/- SD) the correlations between body fatness, adipose tissue
      (AT) distribution measured by computed tomography (CT), and circulating levels of
      the following steroids measured by radioimmunoassay after extraction from serum
      and chromatography: dehydroepiandrosterone (DHEA), androstenedione (delta 4
      DIONE), androst-5-ene-3 beta,17 beta-diol (delta 5-DIOL), T, estrone, and
      estradiol. Sex hormone-binding globulin (SHBG) levels were also determined. T,
      adrenal C19 steroids, and SHBG levels were negatively correlated with total body
      fatness indices and abdominal fat deposition measured by CT (-.23 < or = -.55,
      .0001 < or = P < or = .05), whereas estrone showed positive correlations with
      these body fatness and AT distribution indices. Covariance analysis showed that
      after control for the concentration of the adrenal steroid precursor delta 5
      DIOL, there was no residual association between T levels and adiposity variables.
      Furthermore, multivariate analyses showed that steroid and SHBG levels could
      explain from 20% (visceral AT area measured by CT) to 40% and 42% (body mass
      index [BMI], waist circumference, and waist to hip ratio [WHR]) of the variation
      in adiposity variables (.0001 < or = P < or = .05), with delta 5-DIOL being the
      best single correlate of body fatness and abdominal fat deposition in
      men.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723676
TI  - Beta-adrenergically mediated thermogenic and heart rate responses: effect of
      obesity and weight loss.
AB  - beta-Adrenergically mediated thermogenic and heart rate (HR) responses, as
      assessed by stepwise intravenous infusion of the beta-agonist isoprenaline (ISO),
      were evaluated by partial regression analysis in a group of men with a wide range
      of body fat (n = 30) and in a subgroup of 16 obese men after weight loss. beta
      Adrenergically mediated thermogenesis (open-circuit ventilated-hood system) was
      blunted in obese subjects, as reflected by a significant positive correlation
      between percent body fat (hydrostatic weighing) and the plasma ISO concentration
      needed to increase resting energy expenditure (EE) by 15% (P < .001). The
      magnitude of the beta-adrenergically mediated HR response was (negatively)
      associated with the basal plasma norepinephrine (NE) concentration (P < .001).
      Weight reduction resulted in a significant increase in thermogenic and HR
      responses in obese subjects. Furthermore, the increase in thermogenic response as
      a result of weight loss was negatively related to the magnitude of thermogenic
      response (P < .01) and positively related to the initial percent body fat (P <
      .05). The increase in HR response as a result of weight loss was positively
      related to the decrease in basal NE (P < .01) and the change in percent body fat
      (P < .05). In conclusion, the degree of adiposity was shown to be negatively
      related to the magnitude of beta-adrenergically mediated thermogenesis, whereas
      the HR response was merely related to basal NE. Since weight loss resulted in a
      significant increase in the thermogenic response, the blunted beta-adrenergically
      mediated thermogenesis does not seem to be a primary factor contributing to the
      development of obesity.

PMID- 7723677
TI  - Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary
      syndrome.
AB  - Polycystic ovary (PCO) syndrome is strongly associated with insulin resistance
      and the accompanying adverse metabolic profile. To distinguish the mechanisms of
      this association, we determined the interactions of PCO with obesity and the
      influence of ameliorating direct androgenic actions via short-term treatment with
      the antiandrogen flutamide. Insulin sensitivity was determined by the
      hyperinsulinemic euglycemic clamp in groups of lean and obese PCO women and
      weight-matched controls. Compared with control values, insulin-mediated glucose
      utilization in PCO women was significantly lower in lean (1.96 +/- 0.17 v 1.24 +/
      0.10, P < .01) and obese (1.23 +/- 0.18 v 1.03 +/- 0.09 mmol/m2/min, P < .01)
      subjects. ANOVA indicated that the effects of obesity and androgenicity are
      independent and additive. In both lean and obese PCO women, treatment with
      flutamide for 1 or 3 months markedly improved the clinical and biochemical
      androgenic features, but did not significantly influence the overall insulin
      sensitivity. A large disparity between individuals in the response to treatment
      correlated significantly with a simultaneous reduction in plasma levels of
      dehydroepiandrosterone sulfate (DHEA-S). Thus in women, PCO and obesity exert
      synergistic effects on insulin resistance. The decreased insulin sensitivity is
      mediated via indirect androgenic actions or nonandrogenic mechanisms. In some
      individuals, a direct effect of androgens might have been masked by a decrease in
      DHEA-S levels.

PMID- 7723679
TI  - Low-dose ovine corticotropin-releasing hormone stimulation test in diabetes
      mellitus with or without neuropathy.
AB  - The function of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated in
      insulin-dependent diabetics without (group I, n = 10) or with (group II, n = 10)
      established symptomatic neuropathy and in age- and weight-matched normal controls
      (n = 11). Since the corticotropin (ACTH)/cortisol response to the minimal
      effective dose of corticotropin-releasing hormone ([CRH] 0.03 microgram/kg body
      weight) represents a useful tool for HPA axis examination, all subjects were
      tested with the low-dose ovine CRH stimulation test. Experiments started at 8:30
      AM, when CRH was injected after two basal blood samples were withdrawn, and
      lasted 2 hours. Basal serum levels of ACTH were similar in the three groups.
      Administration of CRH induced a small but significant increase in ACTH levels in
      all subjects; however, the CRH-induced ACTH increase was significantly higher in
      normal controls than in diabetic groups I and II. Furthermore, a significantly
      lower ACTH response was observed in group II than in group I. In contrast, basal
      and CRH-induced cortisol levels were significantly higher in diabetics than in
      normal controls. Comparisons between diabetic groups showed that both basal and
      stimulated cortisol secretion was significantly higher in group II than in group
      I. When peak ACTH responses to CRH and basal cortisol levels were combined, a
      significant negative correlation was found (r = .545, P < .02). These data show
      that even uncomplicated diabetes mellitus is associated with adrenal
      hyperfunction. Such an alteration is more pronounced in the presence of
      neuropathy.

PMID- 7723678
TI  - Chronic maternal hypoxia retards fetal growth and increases glucose utilization
      of select fetal tissues in the rat.
AB  - The development of intrauterine growth retardation (IUGR) is frequently
      associated with fetal hypoxia, hypoglycemia, and abnormal fetal glucose
      metabolism. To determine the effects of hypoxia (without concomitant
      hypoglycemia) on fetal glucose metabolism, we continuously exposed pregnant rats
      to 10% (10.1 kPa) ambient oxygen from day 15 through day 20 of gestation (term,
      21.5 days) and used radiolabeled 2-deoxyglucose (2DG) to measure in vivo relative
      glucose utilization (rGU) of several fetal tissues on day 20 of gestation. Pair
      fed rats in room-air oxygen were used as controls. Maternal hypoxia resulted in
      significant IUGR, fetal hypoxia and acidosis, and fetal lactate accumulation on
      day 20 of gestation. Following 5 days of hypoxia, rGU values for fetal lung,
      heart, and kidney were increased by 61%, 54%, and 47%, respectively (P < .05).
      rGU values for fetal brain, liver, muscle, and placenta were not significantly
      affected. Fetal plasma glucose concentrations were similar in hypoxic and control
      fetuses. We speculate that the increased rGU of hypoxic fetal tissues is due in
      part to anaerobic metabolism and increased glycolysis.

PMID- 7723680
TI  - Effect of dehydroepiandrosterone on glucose uptake in cultured human fibroblasts.
AB  - Dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) reportedly have
      antidiabetic and antiobesity effects. The effect of DHEA on glucose uptake in
      cultured human fibroblasts was examined. Incubation of cells with
      supraphysiologic concentrations of DHEA (10(-5) mol/L) for > or = 10 hours
      enhanced 2-deoxyglucose (2-DG) uptake significantly (P < .05). Supraphysiologic
      concentrations of insulin (10(-7) mol/L) increased the sensitivity of glucose
      uptake to DHEA. Conversely, the sensitivity of glucose uptake to insulin was
      increased by incubating cells with 10(-6) mol/L DHEA. Both the abundance of
      transcripts encoding glucose transporter-1 (Glut-1) and the maximal velocity
      (Vmax) of 2-DG transport were increased in cultured fibroblasts incubated with
      DHEA. Cultured fibroblasts expressed a specific binding factor with low affinity
      for [3H]DHEA (maximal number of binding sites, 18,496 sites per cell; Kd, 298
      nmol/L). Other androgen hormones exerted a less-marked effect on glucose uptake;
      DHEA-S had no effect. These results suggested that DHEA increases Glut-1 mRNA
      through binding to a specific factor in cultured human fibroblasts and thereby
      stimulates glucose uptake in these cells.

PMID- 7723681
TI  - Effect of nibbling versus gorging on cardiovascular risk factors: serum uric acid
      and blood lipids.
AB  - Nibbling has been reported to decrease serum cholesterol under fasting
      conditions, as well as the incidence of cardiovascular disease. It has been
      suggested that these effects are partly attributable to reduced concentrations of
      serum insulin, which are also observed. However, data on the effects of nibbling
      on serum lipids throughout the day are not available, nor is it known how
      nibbling affects serum uric acid as a further insulin-related risk factor for
      cardiovascular disease. We have attempted to address these issues. Seven healthy
      men consumed identical diets in a randomized crossover design either as three
      meals daily (control) or as 17 meals daily (nibbling) for 2 weeks. On day 13,
      serum lipid levels were measured over the course of the day (12 hours) together
      with the 24-hour urinary excretion of mevalonic acid as an indicator of hepatic
      cholesterol synthesis. Concentrations of uric acid in serum and 24-hour urinary
      excretion of uric acid were also determined. Mean (+/- SE) percent treatment
      differences in day-long total, low-density lipoprotein (LDL), and non-high
      density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B were
      significant, with lower values on the nibbling diet as compared with the control
      diet (8.1% +/- 1.6%, P = .002; 12.2% +/- 2.6%, P = .005; 10.1% +/- 1.6%, P <
      .001; and 9.9% +/- 2.6%, P = .008, respectively). No significant difference was
      seen in the total to HDL cholesterol ratio or in urinary mevalonic acid
      excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723683
TI  - Tumor necrosis factor receptor expression in HIV-1-infected CD4+ T cells.
AB  - We investigated whether HIV-1 can regulate tumor necrosis factor receptor (TNFR)
      expression in SupT-1, a CD4+ T-cell line. The cells were infected with HIV-1
      containing 1,000 cpm RT activity, as early as day 3 after infection and all along
      the culture the supernatant level of core protein p24 was > 250 pg/ml, and on
      days 6 and 9 after infection, p24 was found in 10% of the cells as determined by
      indirect immunofluorescence assay. The cells were growing without loss of
      viability. The study of TNFR expression was based on a microassay for measurement
      of binding of 125I-TNF alpha to cells, in which free and cell-bound ligand
      separation was performed by centrifugation through oil. Scatchard analysis of TNF
      alpha binding on days 6 and 9 after infection revealed a 90% increase in the
      expression of high-affinity membrane receptors in HIV+SupT-1 culture compared
      with uninfected cells (mean +/- S.D. = 501 +/- 148.5 vs. 263 +/- 77.8
      receptors/cell, n = 9, P < 0.001) with no change in dissociation constants (mean
      +/- S.D. = 4.36 +/- 1.06 vs. 4.00 +/- 1.12 x 10(-10) M).

PMID- 7723682
TI  - Seroepidemiological survey of Coxiella burnetii in domestic cats in Japan.
AB  - Cats are assumed to be one of the most important reservoirs of causative agent of
      human Q fever especially in urban areas. There is no evidence of Coxiella
      burnetii infection in cats in Japan prior to this. Sera from 100 cats, collected
      in various parts of Japan, were examined for antibody against C. burnetii.
      Sixteen out of the 100 samples contained antibodies against C. burnetii. The
      prevalence of the antibody decreased from the northeastern to the southwestern
      part of Japan. A high prevalence of the antibodies was observed in sera from cats
      of more than four years of age. It is difficult to deny that cats would be one of
      the important sources of human Q fever in Japan.

PMID- 7723684
TI  - Molecular and immunological characterization of the fimbriae of Porphyromonas
      gingivalis.

PMID- 7723686
TI  - Inducement of respiratory mucosal immunogenicity for nasal vaccine due to amine-
      and amide-inactivation of parainfluenza virus type 1, Sendai.
AB  - The protective effects in mice by nasal vaccination of amine- and amide
      inactivated Sendai viruses were investigated by a contact exposure experiment,
      immunofluorescent examination of the entire respiratory tract, and checking the
      serum HI antibody development. Of 10 monoamines, ethanolamine and 2
      methoxyethylamine vaccines induced complete protection, and methylamine,
      ethylamine, n-propylamine, n-butylamine, 2-ethoxyethylamine, diethylamine and
      triethylamine vaccines brought about almost complete protection or lower
      respiratory infection. The methoxyamine-treated mouse conferred the least
      protection. Of 5 diamines, 1,3-diaminopropane vaccine inhibited completely the
      infection, but hydrazine, ethylenediamine, putrescine, and cadaverine vaccines
      produced regional infection. Two polyamines, spermine and spermidine, did not
      inactivate the virus. Of 4 amides, only semicarbazide vaccine conferred complete
      mucosal defense, while acetamide, propionamide, and isonicotinic acid hydrazide
      vaccines lead to regional infection. Serum HI titers developed by vaccination
      were low on the whole, following their slight rise, fall or maintenance
      postexposure. In effect, the 4 vaccines inactivated by a best-suited interstrand
      cross-link between phosphate groups in helix of viral RNA brought about the
      strongest protection, and showed the necessity of a definite length of molecules
      for inactivants.

PMID- 7723685
TI  - Isolation and characterization of three porin-like proteins from Vibrio
      vulnificus: effect of different growth media on their production.
AB  - The effect of the culture media on the composition of the outer membrane protein
      of Vibrio vulnificus strain 393 from human blood was examined. Only one major
      outer membrane protein, with an apparent molecular weight of 37,000 (37K protein)
      and 34,000 (34K protein), was formed in the cells grown in 3% NaCl-BHI broth and
      chemically defined medium, respectively. The production of one major outer
      membrane protein was also observed in other isolates from humans and asari clam
      when they were grown in 3% NaCl-BHI broth. On the other hand, three major outer
      membrane proteins, with apparent molecular weights of 48,000 (48K protein),
      37,000 (37K protein), and 34,000 (34K protein), were produced in the cells grown
      in 3% NaCl-nutrient broth. Three proteins, 48K, 37K, and 34K from strain 393,
      were purified and the amino acid compositions were determined. Although there was
      a little difference in the composition of amino acid among three proteins, the
      amino acid compositions of the three porin-like proteins showed characteristic
      properties of the porins of Escherichia coli and Salmonella typhimurium.
      Immunoblot analysis of the outer membrane proteins from four vibrios, E. coli,
      and S. typhimurium using monospecific antisera against these three porin-like
      proteins showed that only the antiserum against 37K protein cross-reacted with
      the outer membrane proteins from all the strains tested.

PMID- 7723687
TI  - Alteration of immune responses of rabbits infected with bovine immunodeficiency
      like virus.
AB  - Nine 3-month-old rabbits were inoculated with bovine immunodeficiency-like virus
      (BIV) to study the pathogenesis of BIV and alteration of the immune responses in
      experimentally infected rabbits. BIV proviral DNA and anti-BIV antibodies were
      detected from all rabbits inoculated with BIV-infected bovine embryo spleen
      (BESP) cells. Rabbits inoculated with spleen cells of the BIV-infected rabbit
      also converted to proviral DNA-positive and BIV-antibody-positive. The
      blastogenic responses to concanavalin A of peripheral blood mononuclear cells
      prepared from BIV-infected rabbits were not significantly different from those
      from uninfected controls at 2 and 4 months post-inoculation (PI). The humoral
      immune responses against bovine serum albumin (BSA) were depressed in two of four
      BIV-infected rabbits at 1 to 3 months PI. The antibody responses against sheep
      red blood cells (SRBCs) were significantly depressed in all BIV-infected rabbits
      at 2 to 4 months PI. BIV was rescued by cocultivation of spleen cells of infected
      rabbits with BESP cells. Distinct development of lymphoid follicle was observed
      in lymph nodes and spleens of uninfected rabbits which received BSA and SRBCs. In
      contrast, moderate lymphoid cell depletion was observed in BIV-infected rabbits
      which received the same immunogens.

PMID- 7723688
TI  - Studies on serological cross-reaction in sequential flavivirus infections.
AB  - Acute- and convalescent-phase sera from patients with dengue (DEN) hemorrhagic
      fever (DHF) and Japanese encephalitis (JE) that contained pre-existing flavivirus
      antibodies were tested for cross-reacting antibodies to DEN, JE and yellow fever
      (YF) viruses by a neutralization (N) test. A fourfold or greater rise in N
      antibody titer in the convalescent-phase was considered significant. Of 39 DHF
      cases, obtained at Chiang Mai University Hospital, Thailand, 15 (38.5%) showed a
      rise in DEN antibody titer, while another 15 (38.5%) showed a significant rise in
      both DEN and JE N antibody titers. On the other hand, eight (61.5%) of 13 JE
      cases obtained at the same Hospital, showed a significant rise in JE antibody
      titer, while two (15.4%) showed a significant rise in both DEN and JE antibody
      titers. Sucrose gradient centrifugation and fractionation of these two cross
      reactive JE sera revealed that IgM class antibody was specific for JE, while IgG
      class antibody was cross-reactive. Of three JE cases with pre-existing YF
      antibody obtained in Okinawa, Japan, two showed a significant rise in YF and JE
      antibodies. Both IgM and IgG class antibodies to YF virus were elevated. These
      results indicate that the cross-reactivity among flaviviruses in different
      subgroups (complexes), was observed quite often, even by the N test, in
      sequential flavivirus infection.

PMID- 7723689
TI  - Thy.1lowCD3- cells sorted from nylon wool-passed bone marrow cells can augment
      the H-2 identical but not non-identical cytotoxic T lymphocyte precursors in
      mixed lymphocyte cultures.
AB  - Thy.1lowCD3- cells obtained from nylon wool-passed murine bone marrow (NW-BM)
      cells by cell sorting did not express CD4, CD8, or T cell receptor-alpha/beta and
      -gamma/delta on their cell surfaces. An extremely limited number of B10.BR (H-2k)
      responder lymph node (LN) cells were stimulated with B10.D2 (H-2d) stimulator
      spleen cells in cultures containing the minimum required dose of rat T cell
      growth factor (TCGF). In these cultures, the generation of cytotoxic T
      lymphocytes (CTL) was very low. B10.BR Thy.1lowCD3- NW-BM cells, added to these
      cultures, could augment the CTL generation vigorously, but neither B10 (H-2b) nor
      B10.D2 cells could. When B10 LN cells were used as responder cells in these
      cultures, B10 Thy.1lowCD3- NW-BM cells could augment the CTL generation, but
      neither B10.BR nor B10.D2 cells could. Similar findings were obtained when Lyt-2+
      cells or Thy.1+L3T4- (CTL precursor) cells sorted from spleen cells were used as
      responder cells. Both elements, rat-TCGF and Thy.1low CD3- NW-BM cells, were
      essential for this augmentation of the CTL generation in this culture system
      because neither one alone could augment generation, and rat-TCGF could be
      replaced by Thy.1+ Lyt-2- helper T (Th) cells sorted from spleen cells. These
      findings showed that NW-BM cells could augment CTL precursors in a self-major
      histocompatibility complex (self-MHC)-antigen restricted manner, and further that
      both NW-BM cells and Th cells had different and independent functions to induce
      CTL.

PMID- 7723691
TI  - Suppression of anti-Candida activity of murine and human neutrophils by
      glucocorticoids.
AB  - Effects of glucocorticoid (GC) compounds on inhibitory activity of neutrophils to
      mycelial growth of Candida albicans were examined by in vitro crystal violet
      staining method with 14 hr coculture. Both GC hormones (hydrocortisone > or = 6 x
      10(-7) M and corticosterone > or = 10(-6)M) and anti-inflammatory GC agents
      (prednisolone > or = 10(-7) M and dexamethasone > or = 10(-8) M) significantly
      suppressed anti-Candida activity of murine casein-induced neutrophils. Anti
      Candida activity of human neutrophils prepared from peripheral blood was also
      suppressed by hydrocortisone (> or = 6 x 10(-7) M). These GC compounds did not
      affect the Candida growth in the absence of neutrophils. Steroidal compounds
      without anti-inflammatory activity, cholesterol, cholic acid, aldosterone did not
      suppress neutrophil activity. These results suggest that GCs at their
      physiological or clinical concentration may suppress anti-Candida activity of
      neutrophils in vivo.

PMID- 7723690
TI  - Signal transmission through MHC class II molecules in a human B lymphoid
      progenitor cell line: different signaling pathways depending on the maturational
      stages of B cells.
AB  - The function of MHC class II HLA-DR molecules expressed on a human B lymphoid
      progenitor cell line FL8.2.4.4 (abbreviated as FL4.4) was examined. FL4.4 cells
      expressed HLA-DR molecules and stimulation of the DR molecules by anti-DR mAb or
      by superantigen TSST-1 induced strong augmentation of homocytic aggregation and
      protein tyrosine phosphorylation in FL4.4 cells. Induced homocytic aggregation in
      FL4.4 consists both of LFA-1/ICAM-1-dependent and -independent pathways as
      revealed by mAb blocking experiments. Metabolic inhibitors, NaN3 and cytochalasin
      B, blocked the induced homocytic aggregation of FL4.4. Early mature Daudi B cell
      lines also showed a similar type of homocytic aggregation by stimulation with
      anti-DR mAb. Daudi cells are more sensitive to protein kinase inhibitors
      herbimycin A and H7 than FL4.4 cells in their blocking of induced homocytic
      aggregation, while W7 showed stronger inhibitory effects on FL4.4 cells than on
      Daudi cells. Western blotting analysis revealed that the stimulation of DR
      molecules induced protein tyrosine phosphorylation of 100-kDa, 90-kDa, 60-kDa and
      55-kDa proteins in FL4.4 cells, while, in Daudi cells 110-kDa, 100-kDa and 80-kDa
      proteins were phosphorylated. These results suggest that different signaling
      pathways through class II molecules are employed depending on the maturational
      stage of B-cell differentiation.

PMID- 7723693
TI  - Identification of Borrelia burgdorferi isolated in Korea using outer surface
      protein A (OspA) serotyping system.
AB  - Two characteristic strains (935T, 934U) of B. burgdorferi isolated from Ixodes
      persulcatus and a wild rodent (Apodemus agrarius) in Korea were selected and
      analyzed by an immunoblot method using the monoclonal antibodies directed to
      different epitopes of outer surface protein A (OspA). The reactive pattern of
      strain 934U with these monoclonal antibodies was identical to that of strains
      belonging to B. afzelii and that of strain 935T was different from other
      isolates. Monoclonal antibody (5TEE3) which is specific to strain 935T did not
      react with any other Western and Japanese isolates. So, it was suggested that
      there exist at least two groups of B. burgdorferi in Korea. One could be
      classified as B. afzelii and the other is a divergent group from three known
      species of B. burgdorferi sensu stricto, B. garinii and B. afzelii.

PMID- 7723692
TI  - Mechanism for macrophage activation against Corynebacterium parvum--participation
      of T cells and its lymphokines.
AB  - It is well known that Corynebacterium parvum activates macrophages to produce
      tumor necrosis factor (TNF). It is suspected that the activation of macrophages
      by C. parvum requires T-cell participation. The purpose of this study was to
      confirm that T cells participate in the activation of macrophages by C. parvum.
      TNF production in vitro from the spleen cells of BALB/c(-)+/+ mice was abrogated
      completely by the pre-treatment of spleen cells with anti-Ia antiserum and
      complement, indicating that Ia+ cells are the source of TNF. TNF production was
      not elicited at all in BALB/c-nu/nu mice. However, there was an increase in the
      number of Ia+ cells as well as an increase in the weight of spleen and liver.
      Supernatant from a culture of spleen cells stimulated with phytohemagglutinin-P
      (a PHA-induced lymphokine) made it possible for BALB/c-nu/nu mice to produce TNF,
      associated with an induction of Lyt-1+ cells and Lyt-2+ cells. However, treatment
      with the lymphokine did not augment the increases of Ia+ cells or liver and
      spleen weights. These results suggest that increasing the number of Ia+ cells is
      not sufficient to bring about TNF production; Ia+ cells must also be stimulated
      by T cells or T-cell lymphokines in order to produce TNF. These results suggest
      that T cells play an essential role in the activation of Ia+ cells against C.
      parvum.

PMID- 7723694
TI  - Isolation and characterization of Staphylococcus aureus mutants which form
      altered cell clusters.
AB  - Staphylococcus aureus FDA 209P produces two extracellular bacteriolytic enzymes,
      51-kDa endo-beta-N-acetylglucosaminidase (GL) and 62-kDa N-acetylmuramyl-L
      alanine amidase (AM), both of which can disperse cell clusters. To characterize
      the physiological roles of these enzymes in vivo, mutants with altered autolysin
      activity were isolated, and their degree of cluster formation in broth culture
      was assessed. Bacteriolytic activities of GL and AM, produced and secreted from
      these mutants into the culture fluid and detected with activity gels, coincided
      well with the degree of cluster formation of the mutants. The mutants with little
      or no enzyme activity grew in clusters, whereas those with high activity grew as
      well-separated cocci, suggesting that these enzymes are involved in cell
      separation of S. aureus in vivo.

PMID- 7723695
TI  - Specialist medical training.

PMID- 7723696
TI  - A General Medical Council report on proposals for the early years of specialist
      training.

PMID- 7723697
TI  - A proposed joint college programme for senior house officer training.

PMID- 7723698
TI  - Implementing Calman: the trainees' viewpoints.

PMID- 7723699
TI  - An overview of educational issues in planning for Calman.

PMID- 7723700
TI  - Medicine and medical specialties.

PMID- 7723701
TI  - Surgery and surgical specialties.

PMID- 7723702
TI  - Training in obstetrics and gynaecology.

PMID- 7723703
TI  - Royal College of Anaesthetists programme.

PMID- 7723704
TI  - Progress in psychiatry.

PMID- 7723706
TI  - Specialist medical training: implementing Calman: summing up.

PMID- 7723705
TI  - Pathology.
AB  - In summary, the College is a long way forward in the preparation for the
      implementation of Calman and the unified training grade. It has identified a
      number of problems that could hinder its implementation and is anxious to
      develop, along with its sister Colleges, a unified approach to these problems to
      ensure that the doctors of tomorrow have an effective and satisfying training
      experience for the benefit of all the patients for whom we care.

PMID- 7723707
TI  - Hospital doctors: training for the future.

PMID- 7723708
TI  - [Genetic technology and the investigative pharmaceutical industry. Prospects for
      the first decade of a new century].

PMID- 7723709
TI  - [Back pain. Epidemiology, causes and treatment possibilities].

PMID- 7723710
TI  - [Iodine administration without risk. Facts on the need and safety of goiter
      prevention with iodized table salt].

PMID- 7723711
TI  - [Trans-fatty acids and atherosclerosis].

PMID- 7723713
TI  - [Incidence of ultrasound detectable liver hematomas after ultrasound controlled
      fine needle puncture with the 0.95 mm cutting biopsy cannula in comparison with
      percutaneous liver biopsy with the 1.4 mm Menghini needle].
AB  - BACKGROUND: Recently, a high incidence of ultrasound-detected hepatic hematomas
      due to percutaneous liver biopsy has been reported. Until yet, little is known
      about the incidence of asymptomatic hepatic hematomas following sonographically
      guided fine-needle biopsy. PATIENTS AND METHODS: For that reason, we carried out
      a prospective study with sonographic examinations before and after liver biopsy
      in 160 patients. 51 patients, aged 50 to 83, median 67 years, with focal liver
      lesions had ultrasound-guided liver biopsy using the 0.95 mm-cut biopsy-needle,
      in 109 patients (17 to 80, median 49 years) with diffuse liver disease
      percutaneous liver biopsy with the 1.4 mm-needle of Menghini was performed.
      RESULT: After fine-needle biopsy none of the 51 patients with focal liver lesions
      displayed liver hematoma on ultrasonography. In the group of patients who
      underwent percutaneous Menghini biopsy a liver hematoma, sized up to 12 x 5 cm in
      diameter, occurred four times (3.7%). CONCLUSION: The results of this study
      indicate that fine-needle biopsy of the liver is a particularly safe diagnostic
      procedure, when compared with percutaneous Menghini biopsy.

PMID- 7723712
TI  - [Protection and "preconditioning" of the human heart during percutaneous
      transluminal coronary angioplasty (PTCA) by intracoronary dipyridamole
      administration].
AB  - BACKGROUND AND AIM: A brief episode of ischemia followed by reperfusion termed
      "ischemic preconditioning" has been identified as a mechanism rendering the
      myocardium more resistant to ischemia. Recently adenosine has been identified as
      an important mediator of ischemic preconditioning. Dipyridamole represents an
      important drug interfering with myocardial adenosine metabolism by inhibiting its
      degradation. The aim of this study was to investigate the effect of an
      intracoronary dipyridamole infusion on the extent and tolerance of myocardial
      ischemia during percutaneous transluminal coronary angioplasty (PTCA). PATIENTS
      AND METHODS: In the first study group 46 patients undergoing coronary angioplasty
      were randomised to receive dipyridamole or conventional treatment before PTCA. In
      the second study group 11 patients were investigated, receiving PTCA of
      restenosis following PTCA carried out 6 months earlier. RESULTS: In the first
      group as a striking result patients receiving pretreatment with dipyridamole
      tolerated longer times of balloon inflations (155.3 +/- 68.9 vs. 93.1 +/- 24.7
      s), expressed lower severity of cardiac pain, demonstrated less pronounced ST
      segment shifts on the surface ECG and showed a lower incidence of arrhythmias. In
      the second group the first dilatation had been performed conventionally, while
      pretreatment with dipyridamole had been performed prior to the dilatation of
      restenosis. Similar to the findings in the first patient group pretreatment with
      dipyridamole resulted in enhancement of balloon inflation times, regression in
      cardiac pain and lower extent of ST-segment shift and incidence of arrhythmias.
      In both study groups intracoronary application of dipyridamole showed no
      significant impact on heart rate and arterial blood pressure. CONCLUSION:
      Summarising our results indicate, that intracoronary application of dipyridamole
      renders the heart more resistant to ischemia.

PMID- 7723714
TI  - [TNF-alpha level in the vitreous body. Increase in neovascular eye diseases and
      proliferative diabetic retinopathy].
AB  - BACKGROUND: Deficient retinal capillary perfusion results in angioneogenesis of
      the eye. Its extension depends on the degree of ischemia. Mild stages are
      restricted to the retina, while marked ischemia results in neovascularization of
      the iris (rubeosis iridis). The neovascularization may be induced by the release
      of growth factors into the vitreous. Tumor necrosis factor alpha seems to be an
      important angiogenetic growth factor. PATIENTS AND METHODS: The patients were
      divided up into three groups with different retinal stages of ischemia, as judged
      by the extension of new vessel formation of the eye: a control group without
      angioneogenesis, a diabetes group with less severe to moderate angioneogenesis of
      patients with proliferative diabetic retinopathy and a rubeosis group with
      massive angiogenesis (rubeosis iridis) resulting from different causes. TNF-alpha
      was determined by immunological methods. RESULTS: The TNF-alpha level of vitreous
      in rubeosis (25.8 pg/ml; n = 6) was 2-fold elevated compared to controls (13.1
      pg/ml; n = 10; p < 0.05) and 1.4-fold elevated compared to the diabetes group
      (18.2 pg/ml; n = 17). The values ranged from unmeasurable values to 41.25 pg/ml.
      Within the rubeosis group similar changes were observed independently of the
      causes of ischemia. There was no correlation between TNF-alpha-levels in the
      diabetes group and serum creatinine. CONCLUSIONS: 1. TNF-alpha is upregulated in
      ischemia. 2. TNF-alpha seems to be a mediator of angiogenesis in the eye. 3.
      Changes in diabetes may be secondary to local ischemia rather than being specific
      for diabetic retinopathy.

PMID- 7723715
TI  - [Sarcoidosis and chronic idiopathic thrombocytopenic purpura].

PMID- 7723716
TI  - [Therapy of acute respiratory failure: noninvasive mechanical ventilation].

PMID- 7723717
TI  - ['94 oncology update].

PMID- 7723718
TI  - [Electrogastrography in diagnosis of gastric motility disorders].

PMID- 7723719
TI  - [Comprehensive and specialty practice-related education in preclinical teaching
      exemplified by neuroanatomy].

PMID- 7723720
TI  - [Infectious endocarditis caused by Erysipelothrix rhusiopathiae].

PMID- 7723721
TI  - [Subacute bromide poisoning caused by a bromine-containing "nerve tonic"].

PMID- 7723722
TI  - [Reactive arthritis and systemic lupus erythematosus. Necessary, useful,
      superfluous aspects].

PMID- 7723723
TI  - [Sjogren syndrome and hepatitis C].

PMID- 7723724
TI  - [Early and middle latency auditory evoked potentials in vertebrobasilar strokes].
AB  - Brainstem auditory evoked potentials (BAEPs) and middle-latency auditory evoked
      potentials (MLAEPs) have been recorded in 67 patients who had a stroke in well
      defined territories of the vertebral and basilar arteries. Either CT scan or MRI
      have been performed in all cases. BAEPs were abnormal in 41/67 patients and
      MLAEPs were abnormal in 25/39 patients. BAEPs abnormalities were either bilateral
      (29/41 cases) or unilateral (12/41 cases). All components of BAEPS were
      unilaterally absent in four cases and bilaterally in one case. Pa component of
      MLAEPs was unilaterally delayed or reduced in five cases and bilaterally in 20
      cases. Considering the topography of the infarct as shown by CT scan or MRI:
      medulla oblongata (13 cases): BAEPSs were normal in nine cases; pons (24 cases):
      BAEPs were abnormal in 16 cases; MLAEPs were abnormal in ten of 15 patients whose
      BAEPs were abnormal as well; mesencephalon (seven cases): BAEPs were abnormal in
      only two cases, and MLAEPs were abnormal in two cases one of which BAEPs were
      normal; in patients with diffuse infarctions either BAEPs or MLAEPs or both were
      abnormal in all cases. Stimulation of the ear ipsilateral to the lesion disclosed
      more BAEPs or MLAEPs abnormalities than stimulation of the contralateral ear.

PMID- 7723725
TI  - BIT-mapped somatosensory evoked potentials in the fragile X syndrome.
AB  - Middle-latency somatosensory evoked potentials (MLSEPs) were recorded from 19
      scalp electrodes in ten male patients with the fragile X (fraX) syndrome and nine
      normal controls. One fraX patient was found presenting the so-called "giant"
      MLSEPs with an amplitude of N60 of about 60 microV and of 40 microV after
      stimulation of the right and left median nerves, respectively. Tapping of the
      right hand, in the same patient, induced the appearance of left parietal evoked
      EEG spikes. These findings further support the already suggested similarity
      between the epileptic picture of several fraX patients with that of the benign
      childhood epilepsy with centrotemporal spikes. Color mapping of the MLSEPs
      recorded in the remaining nine patients, when compared with the control group,
      showed an abnormally large N30 over the frontal regions, together with an
      increase in amplitude of P27, over the parietal areas, and of N60 and P100 which
      also presented abnormal field distributions, being represented preferentially
      over the frontal regions. These data could suggest the existence of a cortical
      dysfunction mostly involving the frontal lobes (supplementary motor area, in
      particular) in the fraX syndrome which could support many behavioral changes
      usually observed in these patients.

PMID- 7723727
TI  - [Value of a rapid method to determine muscle fiber density in amyotrophic lateral
      sclerosis].
AB  - We shortened single fiber electromyography examination by evaluating fiber
      density, jitter and block numbers in the 10th and the 20th different needle
      positions in the extensor digitorum communis. The results obtained in 15 normal
      subjects and 12 amyotrophic lateral sclerosis patients were comparated. There
      were no significant differences with the 10th and 20th needle positions in normal
      subjects or in patients. This method diminished patient discomfort and shortened
      the examination time.

PMID- 7723726
TI  - Abnormal projection of corticospinal tracts in a patient with congenital mirror
      movements.
AB  - A 31 year-old woman with familial congenital mirror movements not associated with
      other neurological defects underwent a detailed neurophysiological evaluation
      including: voluntary electromyographic activity recorded from upper limbs in
      response to acoustic stimuli, motor evoked potentials from the thenar muscles to
      focal transcranial magnetic stimulation, F waves from upper extremities, scalp
      somatosensory evoked potentials and long-latency responses from thenar muscles to
      electric stimulation of the median nerve. The results were consistent with the
      presence of fast-conducting pathways connecting each hand motor cortex with both
      contra- and ipsilateral spinal motoneurones.

PMID- 7723728
TI  - Sequestration and recycling of beta 2-adrenergic receptors permit receptor
      resensitization.
AB  - Stimulation of beta 2-adrenergic receptors in intact cells causes, first, rapid
      functional uncoupling from Gs, which is triggered by receptor phosphorylation,
      and, second, somewhat slower sequestration of the receptors to an internal
      compartment. The present study addresses a possible role of sequestration in the
      resensitization of desensitized beta 2-adrenergic receptors in human A431 cells.
      Exposure of these cells to isoproterenol caused rapid phosphorylation,
      desensitization (as assessed in adenylyl cyclase assays), and sequestration of
      the receptors. Subsequent removal of the agonist led to recycling of the
      receptors to the cell surface, dephosphorylation, and restoration of receptor
      function. These effects occurred without any change in the total receptor number.
      The rate constant of agonist-induced sequestration was 0.03/min; the rate
      constant of receptor recycling was 0.06/min and was not markedly altered by the
      presence of agonist. Blockade of sequestration with concanavalin A or 0.6 M
      sucrose prevented receptor dephosphorylation as well as receptor resensitization.
      Inhibition of protein phosphatases with calyculin A caused a similar blockade of
      beta 2-adrenergic receptor resensitization; the effects of maximally effective
      concentrations of concanavalin A and calyculin A were not additive. Monensin
      impaired recycling of desensitized beta 2-adrenergic receptors to the cell
      surface and also prevented receptor resensitization. We conclude that
      sequestration of beta 2-adrenergic receptors, followed by dephosphorylation and
      recycling to the cell surface, may serve to restore the function of desensitized
      receptors.

PMID- 7723729
TI  - Regulation of the constitutive expression of the human CYP1A2 gene: cis elements
      and their interactions with proteins.
AB  - Cytochrome P4501A2 (CYP1A2) is a member of the cytochrome P450 family that is
      involved in phase I drug metabolism in vertebrates. To understand how the
      constitutive expression of the human CYP1A2 gene is regulated, its 5' flanking
      region was analyzed. The promoter activity of a human CYP1A2 gene sequence [base
      pairs (bp) -3203 to +58 bp] was measured in transiently transfected HepG2 cells
      using fusion constructs containing the luciferase reporter gene. Using 5'-end
      deletion analysis, two functionally important cis elements, i.e., a proximal 42
      bp DNA from bp -72 to bp -31 and a distal 259-bp DNA from bp -2352 to bp -2094,
      were identified. The proximal sequence (bp -72 to -31) contained CCAAT and GC
      boxes, with which well characterized transcription factors such as nuclear factor
      1/CCAT transcription factor and simian virus 40 promoter factor-1 could interact.
      With regard to the 259-bp fragment (bp -2352 to bp -2094), gel mobility shift
      analyses with HepG2 nuclear lysates indicated high affinity, specific
      interactions of several trans-acting factors. Three protein binding sites within
      the 259-bp fragment were identified by DNase 1 footprinting analysis; these sites
      contained activator protein-1, nuclear factor-E1.7, and one-half hepatic nuclear
      factor-1 (HNF-1) binding consensus sequences. Only the region from bp -2124 to bp
      -2098, in which the HNF-1 binding site was located, was markedly protected by a
      HepG2 nuclear extract, compared with a MCF7 human breast cancer nuclear extract.
      These results suggested that the 259-bp DNA fragment contained positive regulator
      binding sites and HNF-1 could contribute to the liver-specific expression of
      human CYP1A2.

PMID- 7723730
TI  - Topoisomerase II alpha promoter trans-activation early in monocytic
      differentiation of HL-60 human leukemia cells.
AB  - The cytotoxic efficacy of antitumor drugs targeted at DNA topoisomerase II (topo
      II) in many cases varies in direct proportion to cellular topo II content. To
      investigate the transcriptional control of the predominant alpha form of topo II,
      the 5' flanking region of the human topo II alpha gene (positions -562 to +90)
      was subcloned into a firefly luciferase reporter plasmid and transiently
      transfected into HL-60 human leukemia cells, a line capable of monocytic
      differentiation after treatment with various agents. Early in phorbol-12
      myristate-13-acetate (30 nM)-induced differentiation (18-24 hr after treatment),
      an unexpected 3-5-fold activation of topo II alpha gene promoter activity was
      observed. Activation was observed in HL-60 cells and U-937 cells, but not in HeLa
      human cervical carcinoma cells. Sodium butyrate (NaB) (0.4 mM) also led to
      activation (4-17-fold) of the topo II alpha promoter in HL-60 and U-937 cells.
      Promoter sequences between position -90 and position +90 mediated the inducing
      effects of NaB. This NaB-dependent promoter-reporter induction was partly
      mirrored by a transient approximately 2-fold increase in endogenous topo II alpha
      enzyme. The stimulus for promoter activation could be partly attributed to a 2
      fold increase in DNA synthesis at 16 hr for NaB, but not phorbol-12-myristate-13
      acetate. Regardless of the primary stimulus for topo II alpha promoter trans
      activation, it could be bypassed by treatment of HL-60 cells with NaB for 48 hr
      before transfection, revealing the expected 60-70% suppression of topo II alpha
      promoter activity. Further study of topo II alpha promoter down-regulation later
      in monocytic differentiation may serve as a model for elucidating the
      transcriptional mechanisms that may also be exploited by tumor cells expressing
      intrinsic or acquired resistance to topo II-directed drugs.

PMID- 7723731
TI  - Comparison of fura-2 imaging and electrophysiological analysis of murine calcium
      channel alpha 1 subunits coexpressed with novel beta 2 subunit isoforms.
AB  - A polymerase chain reaction product was used to isolate mouse brain cDNA clones
      coding for isoforms of the beta subunit of voltage-dependent Ca2+ channels. The
      two mouse brain beta 2 subunit cDNA clones described, beta 2a and beta 2b,
      differed by alternative splicing within the coding region but possessed a unique
      amino terminus not yet reported in other beta 2 subunit cDNAs. Northern blot and
      RNase protection analyses demonstrated that both mRNA isoforms could be detected
      in highest abundance in heart and brain and at lower levels in lung, kidney, and
      testis. In a novel assay for beta 2 subunit function, COS-1 cells were
      transfected with alpha 1 and beta 2 subunit expression vectors and assayed for
      increases in intracellular Ca2+ concentration by using fura-2 imaging. Co
      transfection of COS-1 cells with the mouse brain class C-1 alpha 1 subunit
      expression vector and either of the beta 2 subunit expression vectors resulted in
      increases in intracellular Ca2+ concentration after stimulation with elevated K+
      and the dihydropyridine agonist Bay K 8644. Transfection of either alpha 1 or
      beta 2 subunit expression vectors alone did not result in an elevation of
      intracellular Ca2+ concentration. Electrophysiological recording of human
      embryonic kidney 293 cells transfected with the expression vector for the alpha 1
      subunit alone or with either beta 2 subunit demonstrated expression of voltage
      dependent Ca2+ channels that were dihydropyridine sensitive. Currents formed by
      expression of only the alpha 1 subunit were small and slowly inactivated. In
      contrast, the currents formed by coexpression of alpha 1 subunits with either
      beta 2 subunit were larger and inactivated more rapidly. Dihydropyridine binding
      studies demonstrated that coexpression of alpha 1 subunits with beta 2 subunits
      increased the density of functional receptors, compared with expression of alpha
      1 subunits alone. These experiments suggested that coexpression of the alpha 1
      and beta 2 subunits produced functional dihydropyridine-sensitive Ca2+ channels
      and that both beta subunit isoforms had modulatory effects on these channels.

PMID- 7723732
TI  - Novel subpopulation of neuronal acetylcholine receptors among those binding alpha
      bungarotoxin.
AB  - Neuronal acetylcholine receptors (AChRs) that bind alpha-bungarotoxin (alpha Bgt)
      (alpha Bgt-AChRs) have previously been found to contain at least one of the alpha
      7-alpha 9 gene products. No other gene products of the 11 neuronal AChR genes
      cloned to date from rat and/or chick have been identified in such receptors.
      Chick ciliary ganglia have about 20 fmol of alpha Bgt-AChRs that contain alpha 7
      subunits and 5 fmol of synaptic-type AChRs that bind the monoclonal antibody
      (mAb) 35 and collectively contain alpha 3, beta 4, alpha 5, and, to a lesser
      extent, beta 2 subunits. Using a sensitive solid-phase immunoprecipitation assay,
      we show here that ciliary ganglia have about 1 fmol of novel putative AChRs that
      bind both alpha Bgt and mAb 35 but appear to lack all of the known neuronal AChR
      gene products in ciliary ganglia, including alpha 3, alpha 5, alpha 7, beta 2,
      and beta 4. The putative receptors are also unlikely to contain either alpha 8 or
      alpha 9 gene products, because of the known expression patterns of these gene
      products. Nonetheless, the component sediments at 10 S, as expected for neuronal
      AChRs, and has a nicotinic pharmacology similar but not identical to that of
      alpha 7-containing alpha Bgt-AChRs. The AChR alpha 1 gene product expressed in
      muscle is known to bind both alpha Bgt and mAb 35, and we show here that ciliary
      ganglia contain small amounts of alpha 1 transcript. The putative ciliary
      ganglion AChR defined by joint alpha Bgt and mAb 35 binding, however, does not
      appear to contain alpha 1 subunits. A similar component binding both mAb 35 and
      alpha Bgt can be detected in sympathetic ganglia and dorsal root ganglia but not
      in brain, spinal cord, or retina. The developmental time course of the component
      in ciliary ganglia is comparable to that of the alpha 7-containing alpha Bgt
      AChRs. If the component is a functional AChR on ciliary ganglion neurons, as
      seems likely, it would represent the fourth AChR subtype produced by this
      population of cells. Our inability to identify subunits comprising the putative
      receptors raises the possibility that additional AChR genes remain to be cloned.

PMID- 7723733
TI  - Adaptive supersensitivity and the Na+/K+ pump in the guinea pig vas deferens:
      time course of the decline in the alpha 2 subunit.
AB  - Adaptive supersensitivity in the guinea pig vas deferens has been shown
      previously to be associated with decreases in transmembrane potential, Na+/K+
      ATPase activity, [3H]ouabain binding sites, and density of the alpha 2 subunit of
      the pump. One of several procedures that induce adaptive supersensitivity in the
      guinea pig vas deferens is neurotransmitter depletion by chronic administration
      of reserpine. Guinea pigs were treated with reserpine (1.0 mg/kg/day,
      intraperitoneally) for 2, 5, or 8 days. Tissues were homogenized and the
      concentration of the alpha 2 subunit was quantified by use of the selective
      antibody McB2, slot blot analysis, enhanced chemiluminescence, and densitometric
      analysis. As reported previously, the concentration of the alpha 2 protein was
      reduced 41% after 5 days of pretreatment. The reduction was maintained at 8 days
      (37%). However, there was no change from control after 2 days of pretreatment
      with reserpine. Thus, the time course of the decline in the alpha 2 subunit is
      similar to that of the appearance of supersensitivity, depolarization, and the
      declines in Na+/K+-ATPase and [3H]ouabain binding established earlier. Based upon
      results in the literature for several different tissues and species, membrane
      depolarization and decreases in Na+/K+ pump sites may represent widely occurring
      adaptive mechanisms.

PMID- 7723734
TI  - Antibodies to the cloned mu-opioid receptor detect various molecular weight forms
      in areas of mouse brain.
AB  - Polyclonal antibodies directed against the amino-terminal portion of the cloned
      rat mu-opioid receptor (muOR) were raised in rabbits. The antibodies diminished
      the specific binding of 125I-Tyr27-beta-endorphin-(1-31) (human) and [3H][D
      Ala2,N-MePhe4,Gly-ol5]enkephalin, but not that of the delta OR-selective ligand
      [3H][D-Pen2,5]enkephalin, to mouse brain membranes. The intracerebroventricular
      administration to mice of affinity-purified anti-muOR IgGs impaired the
      antinociception produced by the muOR agonists [D-Ala2,N-MePhe4,Gly-ol5]enkephalin
      and morphine and the mu/delta OR agonists beta-endorphin-(1-31) and [D-Ala2,D
      Leu5]enkephalin, when studied 24 hr later in the tail-immersion test.
      Antinociception produced by the delta OR-selective agonists [D-Pen2,5]enkephalin
      and [D-Ala2]deltorphin II was fully displayed in these mice. Immunoblots of
      sodium dodecyl sulfate-solubilized membranes from mouse central nervous system
      regions revealed protein bands of M(r) 43,000, 51,000, and 58,000. Also detected
      were bands of higher molecular weights, 100,000 and 114,000, which probably
      corresponded to dimeric forms, because they disappeared after sonication of the
      solubilized tissues. This immunoreactivity was present in regions of mouse
      central nervous system and was barely detected in NG108-15 cells. After treatment
      of the solubilized material with endoglycosidase F, the antibodies labeled a band
      of M(r) 43,000, coincident with the weight of the cloned muOR. These results
      confirm the existence of several molecular forms of the muOR due to
      glycosylation.

PMID- 7723735
TI  - Tau phosphorylation in brain slices: pharmacological evidence for convergent
      effects of protein phosphatases on tau and mitogen-activated protein kinase.
AB  - Tau is a neuron-specific, microtubule-associated protein that forms paired
      helical filaments (PHFs) of Alzheimer's disease when aberrantly phosphorylated.
      We have attempted to elucidate the protein kinases and phosphatases that regulate
      tau phosphorylation. Incubation of rat, human, and rhesus monkey temporal
      neocortex slices with the phosphatase inhibitor okadaic acid induced epitopes of
      tau similar to those found in PHFs. Okadaic acid (1-20 microM) induced variant
      forms of tau at 60-68 kDa, which were recognized by the monoclonal antibodies Alz
      50 (in humans only) and 5E2 and two polyclonal antipeptide antisera, OK-1 and OK
      2. The phosphorylation-sensitive monoclonal antibody Tau-1 failed to recognize
      the slowest mobility forms of tau after okadaic acid treatment. FK-520 (1-10
      microM), a potent inhibitor of calcineurin activity, was tested in brain slices
      and found not to alter tau mobility. However, combinations of FK-520 (5 microM)
      and okadaic acid (100 nM) caused tau mobility shifts similar to those seen after
      10 microM okadaic acid treatment; similar results were seen using the calcineurin
      selective inhibitor cypermethrin. Treatment of human slices with 10 microM
      okadaic acid decreased both protein phosphatase 2A and calcineurin activity; FK
      520 inhibited only protein phosphatase 2B activity. A proposed tau-directed
      kinase, 42-kDa mitogen-activated protein kinase (p42mapk), was activated by
      okadaic acid (> 100 nM) but not FK-520 (5 microM). Nerve growth factor (100
      ng/ml) activated p42mapk, particularly when used in combination with 100 nM
      okadaic acid; changes in tau mobility were seen when this kinase was activated.
      Forskolin (2 microM) antagonized the effects of nerve growth factor on both
      p42mapk activity and tau phosphorylation; forskolin alone had little effect on
      PHF-like tau formation induced by phosphatase inhibitors. These results outline
      complex interactions between tau-directed protein kinases and protein
      phosphatases and suggest potential sites for therapeutic intervention.

PMID- 7723736
TI  - Nitric oxide-induced apoptosis in RAW 264.7 macrophages is antagonized by protein
      kinase C- and protein kinase A-activating compounds.
AB  - Endogenously generated or exogenously applied nitric oxide (NO) redox species
      induce apoptotic cell death in murine RAW 264.7 macrophages. Activation of the
      inducible NO synthase by incubation of cells with a combination of
      lipopolysaccharide and interferon-gamma produced internucleosomal DNA
      fragmentation and morphological alterations, i.e., chromatin condensation,
      indicative of apoptotic cell death. These alterations, reflecting the production
      of NO, were prevented by an inhibitor of NO synthase, NG-monomethyl-L-arginine.
      Moreover, NO derived from endogenous or exogenous sources caused accumulation of
      the tumor suppressor gene p53. Proposing a link between NO generation and DNA
      fragmentation, we investigated interfering biochemical signaling pathways.
      Therefore, we tested the ability of four NO-releasing compounds [sodium
      nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1), S-nitroso-N
      acetylpenicillamine (SNAP), and S-nitrosoglutathione (GSNO)] to cause specific
      DNA fragmentation. All NO donors induced DNA fragmentation in a time- and
      concentration-dependent manner. However, substance-specific differences became
      obvious. After an 8-hr incubation period, GSNO proved to be the strongest
      apoptotic inducer, whereas SIN-1 was much less active. Apoptosis was rapid with
      GSNO and SNP, yielding specific DNA fragments after 4 hr and 5 hr, respectively.
      In contrast, SNAP and SIN-1 produced DNA fragmentation after considerable lag
      times of 9 hr and 14 hr, respectively. Furthermore, an inhibitory effect of
      protein kinase C (PKC) and cAMP-dependent protein kinase became apparent. 12-O
      Tetradecanoylphorbol-13-acetate, an activator of PKC, inhibited DNA fragmentation
      by all four NO donors, whereas PKC inhibitors such as staurosporine and
      calphostin C sensitized macrophages to apoptosis induced by SNP and GSNO.
      Lipophilic cAMP analogues suppressed SNP-, SIN-1, and SNAP-induced DNA
      fragmentation. Thus, our study suggests the existence of specific down-modulatory
      mechanisms related to NO-induced apoptotic DNA fragmentation.

PMID- 7723737
TI  - Protein-independent lead permeation through myelin lipid liposomes.
AB  - We have investigated the permeability of protein-free myelin lipid liposomes to
      inorganic lead by using the fluorescent probes fura-2, oxonol V, pyranine, and
      carboxyfluorescein. Inorganic lead readily crossed the lipid bilayer, as detected
      with fura-2, to an extent that depended on the external pH and the total nominal
      lead concentration in the assay medium. Lead entry generated an internally
      positive transmembrane potential, which could be detected by oxonol V
      fluorescence quenching, and dissipated a transmembrane pH gradient by
      alkalinization of the intravesicular space, as measured with pyranine. These
      results cannot be explained by lead-mediated nonspecific damage to membrane
      lipids, based on the following results 1) lead exposure did not increase
      carboxyfluorescein leakage from liposomes, 2) it did not increase the
      permeability of the lipid bilayer to glucose or KCl, 3) it did not generate
      peroxidation products in contact with myelin lipids, and 4) it did not induce
      chemical hydrolysis or modification of any myelin lipid class. We conclude that
      the principal molecular mechanism of lead permeation through a pure lipid bilayer
      is the passive diffusion of Pb(OH)+. We discuss the toxicological relevance of
      these findings for cells in general and for myelin in particular and suggest that
      this mechanism might contribute significantly to the total lead entry into the
      cells.

PMID- 7723738
TI  - Beta-adrenoceptor-G alpha S coupling decreases with age in rat aorta.
AB  - beta-Adrenoceptor (beta AR) responsiveness, receptor density, receptor-G protein
      coupling, and the possible role of membrane fluidity in receptor-G protein
      coupling were investigated in the rat aorta with age. The beta AR agonist
      isoproterenol (ISO) produced relaxation of KCl-induced aortic contractions by
      97%, 21%, and 0% in aortae from 1- 6-, and 24-month-old Fischer 344 rats,
      respectively. Forskolin completely relaxed the contractions at all ages. beta AR
      density was determined in aortic membranes by saturation binding of 125I
      cyanopindolol (125I-CYP). beta AR density was 76, 52, and 47 fmol/mg of protein
      in 1-, 6-, and 24-month-old rats, respectively. To investigate beta AR coupling
      to G proteins, displacement by ISO of 125I-CYP binding was determined in aortic
      membranes in the presence and absence of the GTP analog guanosine-5'-(beta gamma
      imido)triphosphate [Gpp(NH)p] (0.1 mM). The effect of Gpp(NH)p on the ISO
      displacement curve for 125I-CYP binding was greatest in 1-month-old rats and
      decreased markedly with age. In 1-month-old aorta, in the absence of Gpp(NH)p the
      ISO displacement curve was biphasic and two affinity constants were determined
      (KH - 0.061 microM and KL = 2.4 microM). In the presence of Gpp(NH)p the ISO
      displacement curve was monophasic (Kd - 0.72 microM). In 6-month-old aorta,
      whereas an effect of Gpp(NH)p on the ISO displacement curve could still be
      observed [in the absence of Gpp(NH)p, KH = 0.2 microM and KL = 3.5 microM; in the
      presence of Gpp(NH)p, Kd - 0.83 microM], the affinity constant for high affinity
      agonist binding and the percentage of receptors with high affinity for agonist
      were decreased significantly. In 24-month-old aorta there was no effect of
      Gpp(NH)p on the ISO displacement curve and a single affinity constant was
      detected [0.7 microM and 0.8 microM in the presence and absence of Gpp(NH)p,
      respectively]. The presence of two affinity constants for ISO in 1- and 6-month
      old aorta in the absence of Gpp(NH)p and single affinity constants in the
      presence of Gpp(NH)p presumably represent the G protein-coupled and uncoupled
      states of the beta ARs, which are not observed in 24-month-old aorta. The ability
      of the beta AR to form the high affinity nucleotide-sensitive complex with the
      agonist was restored by treatment of the membranes with cis-vaccenic acid, which
      increases the fluidity of the membrane.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7723739
TI  - Selective labeling of the dopamine transporter by the high affinity ligand 3 beta
      (4-[125I]iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester.
AB  - The iodine-125 analog of the dopaminergically selective cocaine analog 3 beta-(4
      iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester (RT1-121) was evaluated
      as a probe for the dopamine transporter in rat striatum. Saturation and kinetic
      studies indicated that [125I]RTI-121 binds to both high and low affinity
      components. The Kd of the high affinity component was 0.14 +/- 0.01 nM (mean +/-
      standard error), whereas the low affinity component demonstrated an affinity of
      1.59 +/- 0.09 nM. The corresponding numbers of striatal binding sites labeled by
      [125I]RTI-121 were 295 +/- 6 and 472 +/- 59 pmol/g of tissue (original wet
      weight), respectively. Intrastriatal injections of 6-hydroxydopamine eliminated >
      90% of specific [125I]RTI-121 binding in the striatum. The pharmacological
      profile of specific [125I]RTI-121 binding in the rat striatum was consistent with
      that of the dopamine transporter. There was a strong (r = 0.98, p < 0.0001)
      correlation between the potencies of drugs that displaced specific [125I]RTI-121
      binding and the potencies of these drugs to inhibit the uptake of [3H]dopamine.
      In contrast, no correlation was found for the potencies of drugs to inhibit the
      uptake of either [3H]norepinephrine or [3H]serotonin. Autoradiographs produced
      using [125I]RTI-121 demonstrated a distribution of label consistent with the
      distribution of dopaminergic neurons in rat brain. Because of its high affinity
      and high selectivity for the dopamine transporter, [125I]RTI-121 may be an
      extremely useful ligand for the dopamine transporter.

PMID- 7723740
TI  - Mastoparan increases the intracellular free calcium concentration in two insulin
      secreting cell lines by inhibition of ATP-sensitive potassium channels.
AB  - The mechanisms underlying mastoparan-induced elevation of the intracellular free
      calcium concentration ([Ca2+]i) were investigated in the insulin-secreting cell
      lines RINm5F and HIT. In both cell types, micromolar concentrations of mastoparan
      induced a prompt increase of [Ca2+]i, measured as an increase in fura-2
      fluorescence. This response was dependent on extracellular calcium entry and was
      suppressed by organic calcium channel blockers; the increase of [Ca2+]i caused by
      high glucose concentrations or tolbutamide was not enhanced by mastoparan. These
      data indicate the involvement of voltage-dependent calcium channels and suggest
      that depolarization, rather than a direct effect on the channels, mediates the
      response to mastoparan. This proposition was supported by the observation that
      whole-cell calcium currents measured using the nystatin-permeabilized patch
      technique were not affected by mastoparan. Mastoparan-induced depolarization was
      observed using the potentiometric indicator bis-oxonol, and it was shown not to
      be additive with the depolarization induced by high glucose concentrations or
      tolbutamide. The mechanism underlying mastoparan-induced depolarization was
      identified in single-channel patch-clamp experiments, where it was shown that
      mastoparan caused closure of ATP-sensitive potassium channels [K(ATP) channels]
      in cell-attached and excised membrane patches. Responsiveness to mastoparan in
      excised patches demonstrated the membrane-delimited character of K(ATP) channel
      inhibition. The observation that the response persisted in the absence of
      exogenous GTP and in the presence of 250 microM GDP or guanosine-5'-O-(2
      thio)diphosphate suggested that this effect is not mediated via enhancement of G
      protein activity. Partial suppression of channel activity by mastoparan did not
      prevent the action of tolbutamide, which fully suppressed the remaining activity
      in excised patches. In summary, the increase of [Ca2+]i in the insulin-secreting
      tumor cell lines RINm5F and HIT in response to mastoparan is mediated via G
      protein-independent suppression of K(ATP) channel activity, cell depolarization,
      and activation of voltage-dependent calcium channels.

PMID- 7723741
TI  - Divergent structural requirements exist for calcitonin receptor binding
      specificity and adenylate cyclase activation.
AB  - The basis of the high potency of salmon calcitonin (sCT) in radioligand binding
      competition and cAMP accumulation studies with cloned calcitonin (CT) receptors
      from rats, pigs, and humans was examined using two sets of CT analogues, i.e.,
      chimeric sCT/human CT (hCT) analogues and analogues of sCT with differing
      capacities to form an amphipathic alpha-helix. In competition for 125I-sCT
      binding the following relative specificities were observed for the chimeric
      peptides: rat C1a CT receptor, sCT > or = (1-16)hCT/(17-32)sCT (ACT-15) > (1
      16)sCT/(17-32)hCT (ACT-27); rat C1b CT receptor, sCT >> ACT-15 > ACT-27; hCT
      receptor, sCT = ACT-15 > ACT-27; porcine CT receptor, sCT > ACT-27 > ACT-15. In
      contrast, in ligand-induced cAMP accumulation studies the relative efficacies
      were as follows: rat C1a CT receptor, sCT = ACT-15 > ACT-27; rat C1b CT receptor,
      sCT = ACT-15 > ACT-27; hCT receptor, sCT = ACT-15 > or = to ACT-27; porcine CT
      receptor, sCT = ACT-15 = ACT-27. The data demonstrate that residues present in
      the carboxyl-terminal half of sCT are more important for binding competition with
      the rat C1a, rat C1b, and human CT receptors, whereas residues in the amino
      terminal half of sCT are more important for binding competition with the porcine
      CT receptor. Carboxyl-terminal sCT residues are also important for full potency
      in adenylate cyclase activation with the rat C1a and rat C1b CT receptors but are
      less important for activation via the hCT receptor. The disparity in the relative
      potencies of the peptides in studies of binding competition and cAMP accumulation
      is suggestive of significant differences in the relative affinities of the
      peptides for active and inactive conformations of the CT receptor. The use of sCT
      analogues with varying capacities to form alpha-helices also revealed divergence
      in the responses of different receptors. This was most apparent for the
      stimulation of cAMP production by the rat receptor isoforms C1a and C1b. In cells
      expressing the C1a receptor, the helical analogues sCT and des-Ser2-sCT were
      equipotent with [Gly8]-des-Leu19-sCT and des-1-amino-[Ala1,7,Gly8]-des-Leu19 sCT,
      analogues that have reduced or absent helical structure, respectively. In
      contrast, the nonhelical analogues were 100-1000-fold less potent than sCT and
      des-Ser2-sCT at the C1b receptor. In general, reduction in the ability of sCT
      analogues to form helix structures had a greater impact on the potency of the
      analogues in competition for 125I-sCT binding than in cAMP accumulation.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7723742
TI  - Inhibition of human 5-phosphoribosyl-1-pyrophosphate synthetase by 4-amino-8
      (beta-D-ribofuranosylamino)-pyrimido[5,4-d]pyrimidine-5'- monophosphate: evidence
      for interaction at the ADP allosteric site.
AB  - The kinetics of inhibition by the aminopyrimidopyrimidine nucleotide 4-amino-8
      (beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine[-5' -monophosphate (APP-MP)
      were assessed with two human isozymes of 5-phosphoribosyl-1-pyrophosphate
      synthetase (PRS) (PRS1 and PRS2) and a mutant enzyme, S.M. PRS1, derived from an
      individual with PRS hyperactivity. In the presence of 1 mM potassium phosphate,
      APP-MP inhibited PRS1 and PRS2 with half-maximal inhibition (IC50) at 5.2 microM
      and 23.8 microM, respectively. The degree of inhibition for both enzymes was
      highly dependent on the phosphate concentration; IC50 values were 70 times higher
      in the presence of 50 mM potassium phosphate. APP-MP exhibited mixed
      noncompetitive-uncompetitive inhibition against PRS1, with a Kii value of 6.1
      microM and a Kis value of 14.6 microM, and produced parabolic secondary plots of
      slope or intercept versus APP-MP concentration. In comparison, inhibition of PRS1
      by ADP was of a mixed noncompetitive-competitive type, with a Kii value of 9.6
      microM and a Kis value of 2.8 microM. A similar kinetic analysis was completed
      using S.M. PRS1, a mutant enzyme with a single amino acid substitution resulting
      in diminished sensitivity to feedback inhibition by nucleotides. The
      noncompetitive component of ADP inhibition of PRS1 was absent with S.M. PRS1 and
      ADP inhibition was purely competitive, with a Ki of 6.4 microM, APP-MP was a very
      poor inhibitor of S.M. PRS1, displaying uncompetitive characteristics and a Ki of
      1.6 mM. These data indicate that APP-MP inhibits PRS1 with a strong element of
      noncompetitive inhibition and appears to interact specifically at the allosteric
      site used by ADP. These results contrast with those obtained with ADP, which has
      a strong component of ATP competitive inhibition and binds at the ATP site as
      well as at a second, allosteric, site.

PMID- 7723743
TI  - Metabolic diversity and antiviral activities of acyclic nucleoside phosphonates.
AB  - The acyclic nucleoside phosphonates (S)-1-(3-hydroxy-2
      phosphonylmethoxypropyl)cytosine (HPMPC), (S)-9-(3-hydroxy-2
      phosphonylmethoxypropyl)adenine (HPMPA), and 9-(2-phosphonylmethoxyethyl)adenine
      (PMEA) inhibited herpes simplex virus-1 replication in Vero cells, and the IC50
      values ranged from 4 microM (for HPMPC and HPMPA) to 40 microM (for PMEA).
      Pretreatment of cells with HPMPC for 12-24 hr induced an effective antiviral
      state, and the cells maintained this antiviral state for > 7 days. In contrast,
      much larger amounts (approximately 2.5-5 x IC50 doses) of PMEA or HPMPA were
      required to establish an antiviral state, which lasted for only approximately 24
      or 72 hr, respectively. A 12-hr treatment of the cells with the phosphonates was
      required for the establishment of optimal antiviral activity; surprisingly,
      longer durations of exposure to PMEA (but not HPMPA or HPMPC) resulted in
      diminished antiviral effect. We investigated the metabolism of PMEA and HPMPC to
      determine the cellular basis for these differences. The cellular uptake of HPMPC
      was approximately 8-fold greater than that of PMEA. The levels of the PMEA
      metabolites PMEA monophosphate and PMEA diphosphate increased for approximately
      12 hr and plateaued thereafter. PMEA and its metabolites were cleared from the
      cells with a half-life of 4.9 hr. In contrast, the HPMPC metabolites HPMPC
      monophosphate (HPMPCp) and HPMPC diphosphate (HPMPCpp) accumulated throughout the
      24-hr study period and, at equimolar drug concentrations (25 microM), reached
      intracellular levels approximately 2-3-fold greater than those of the PMEA
      metabolites. HPMPC also differed from PMEA in its capacity to generate a
      phosphodiester metabolite (HMPCp-choline), which was a predominant metabolite in
      HPMPC-treated cells. In addition, the rates of disappearance of intracellular
      metabolites of the two drugs were significantly different. Thus, the decay of
      HPMPCpp was quite slow and biphasic (t1/2 = 24 and 65 hr) and that of HMPCp
      choline was monophasic (t1/2 = 87 hr). Together, these factors can explain the
      differing antiviral potencies seen with PMEA and HPMPC. The possible role of the
      choline adduct in the expression of antiviral activity of the drug remains to be
      elucidated, but the adduct may serve as an intracellular store for the long term
      maintenance of active HPMPCpp in cells. The results also highlight the extent of
      diversity in the cellular pharmacology and antiviral activities of the acyclic
      nucleoside phosphonates.

PMID- 7723744
TI  - Ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and
      the tyrphostin ST271 inhibit phospholipase C in human platelets by preventing
      Ca2+ entry.
AB  - In the present study, the roles of Ca2+ and fibrinogen receptor occupancy in the
      regulation of phospholipase C by G protein-coupled and tyrosine kinase-linked
      receptor pathways in human platelets have been investigated. Agonist stimulation
      of phospholipase C was not altered significantly in the absence of stirring or in
      the presence of the fibrinogen receptor antagonist arginine-glycine-aspartate
      serine, conditions that prevent platelet aggregation. Similarly, elevation of
      intracellular Ca2+ levels by the ionophores A23187 or ionomycin did not induce
      formation of inositol phosphates. In contrast, chelation of extracellular Ca2+ by
      ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)
      reduced formation of inositol phosphates by G protein receptor (thrombin)- and
      tyrosine kinase (Fc receptor and peroxovanadate)-regulated pathways. Similarly,
      short term exposure to Ni2+ ions, which also prevent Ca2+ entry, inhibited
      thrombin-stimulated formation of inositol phosphates. Loading of platelets with
      the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid (BAPTA) markedly suppressed elevation of intracellular Ca2+ and
      formation of inositol phosphates in platelets stimulated by G protein receptor-
      and tyrosine kinase-regulated pathways. The greater inhibition of phospholipase C
      by BAPTA, relative to that induced by EGTA, is consistent with the more
      pronounced inhibition of intracellular Ca2+ elevation. The tyrphostin tyrosine
      kinase inhibitor ST271 also reduced intracellular Ca2+ levels and inhibited
      activation of phospholipase C. The degree of inhibition of phospholipase C by
      ST271 was slightly greater than that induced by EGTA but was not additive with
      the effect of EGTA, suggesting a common mode of action. It is concluded that
      elevation of intracellular Ca2+ regulates agonist-induced activation of
      phospholipase C and that this contributes to the inhibition of thrombin-induced
      formation of inositol phosphates by the tyrphostin ST271.

PMID- 7723745
TI  - Stimulation of type II adenylyl cyclase by chemoattractant formyl peptide and C5a
      receptors.
AB  - The capacity of N-formylmethionyl-leucyl-phenylalanine (fMLP) and C5a receptors
      to regulate type II adenylyl cyclase was examined in transient transfection
      studies. Coexpression of either one of the chemoattractant receptors with type II
      adenylyl cyclase in human embryonic kidney 293 cells allowed the corresponding
      chemotactic factor to stimulate cAMP accumulation in a dose-dependent manner. The
      chemoattractant-induced stimulation of type II adenylyl cyclase was absolutely
      dependent on the presence of GTP-bound alpha subunit of GS, as revealed by the
      coexpression of alpha s-Q227L, a constitutively activated mutant of alpha s.
      Stimulation of type II adenylyl cyclase by either fMLP or C5a was mediated via
      pertussis toxin-sensitive Gi-like proteins, because the response was abrogated by
      the toxin. The ability of Gz (a pertussis toxin-insensitive G protein that can
      couple to a number of Gi-linked receptors) to replace Gi in chemoattractant
      induced stimulation of type II adenylyl cyclase was examined. The chemoattractant
      induced response became insensitive to pertussis toxin upon coexpression of the
      alpha subunit of Gz. Interestingly, coexpression of alpha z significantly
      enhanced the chemotactic factor-stimulated type II adenylyl cyclase activities.
      When other G protein alpha subunits were tested under similar experimental
      conditions, all three forms of alpha 1 and alpha o1 were able to potentiate the
      fMLP response to various extents, whereas alpha q and alpha t slightly inhibited
      the fMLP response. The alpha subunit-mediated potentiation of the type II
      adenylyl cyclase response appears to reflect a productive coupling between alpha
      subunits and the fMLP receptor, because such enhancements were not seen with the
      constitutively activated alpha subunit mutants. Coexpression of the
      constitutively activated mutants of alpha z, alpha q, alpha 01, and alpha i1-3
      neither enhanced nor inhibited the fMLP-stimulated cAMP accumulation. These
      results indicated that the observed enhancement of type II adenylyl cyclase
      responses was dependent on the ability of the wild-type alpha subunits to
      functionally interact with the fMLP receptor and that the fMLP receptor can
      couple to Gi1-3, Gz, and Go1 but not to Gs, Gq, or Gt.

PMID- 7723746
TI  - Direct block of calcium channels by dioctanoylglycerol in pregnant rat myometrial
      cells.
AB  - The effect of 1,2-dioctanoyl-sn-glycerol (DiC8), a diacylglycerol and potent
      protein kinase C (PKC) activator, on the voltage-dependent slow (L-type) Ca2+
      current [lCa(L)] was examined using whole-cell voltage clamp of myometrial cells
      freshly isolated from late pregnant rats. Bath application of DiC8 (25 microM)
      decreased ICa(L) by 50.7 +/- 2.4% (n = 22). The effect was reversible and dose
      dependent (IC50 of 15.3 microM). The effect of DiC8 was not reversed or prevented
      by application of calphostin C, a selective PKC inhibitor. In addition, 1-oleoyl
      2-acetyl-sn-glycerol, another PKC activator, did not produce an inhibitory effect
      on ICa(L), even at a concentration of 100 microM; ICa(L) was actually slightly
      stimulated (10.6 +/- 5.1%, n = 6). The steady state inactivation curve for ICa(L)
      was shifted to the left by DiC8 application (by approximately 15 mV at 25
      microM), whereas the activation curve was not affected; the shift should produce
      a voltage-dependent block. DiC8 decreased ICa(L) progressively during repetitive
      step depolarizations (use-dependent block). We conclude from these results that
      (a) DiC8 inhibits ICa(L) independently of PKC in uterine muscle cells and (b)
      DiC8 preferentially acts on the inactivated state and/or open state of the L-type
      Ca2+ channels. Therefore, caution must be exercised when studying PKC actions on
      ion channel regulation using DiC8 as a PKC activator.

PMID- 7723747
TI  - Modulation by mu-opioid agonists of guanosine-5'-O-(3-[35S]thio)triphosphate
      binding to membranes from human neuroblastoma SH-SY5Y cells.
AB  - The ability of mu-opioid agonists to activate G proteins has been demonstrated by
      studying the binding of the GTP analogue guanosine-5'-O-(3-[35S]thio)triphosphate
      ([35S]GTP gamma S) to membranes from the human neuroblastoma SH-SY5Y cell line.
      The potent opioid agonist fentanyl caused an approximate doubling of basal
      [35S]GTP gamma S binding in a naloxone-sensitive manner, confirming this to be an
      opioid receptor-mediated process. The presence of GDP was necessary to observe
      this effect. Pretreatment of the cells with pertussis toxin (100 ng/ml, for 24
      hr) completely prevented the fentanyl-stimulated increase in [35S]GTP gamma S
      binding and lowered the basal binding of [35S]GTP gamma S. These latter data
      suggest an involvement of Gi and/or Go proteins and their activation by added
      membrane-bound receptors even in the absence of agonist. The order of potency of
      a series of opioid agonists in stimulating the binding of [35S]GTP gamma S was
      buprenorphine > cyclazocine = levallorphan > nalorphine > [D-Ala2,MePhe4,Gly
      ol5]enkephalin (DAMGO) > fentanyl > morphine > pentazocine. DAMGO, fentanyl, and
      morphine were full agonists but the remaining compounds showed decreasing levels
      of intrinsic activity in the order buprenorphine > pentazocine > cyclazocine =
      nalorphine > levallorphan. The opioid antagonist naloxone was without effect.
      Under the conditions of the [35S]GTP gamma S assay, binding of agonists was to a
      high affinity site, indicating that a high agonist affinity state of the mu
      opioid receptor is responsible for the observed stimulation of [35S]GTP gamma S
      binding. The level of [35S]GTP gamma S binding (597 fmol/mg of protein)
      stimulated by DAMGO was 2-fold greater than the maximal number of mu-opioid
      agonist binding sites (Bmax) determined using [3H]DAMGO (254 fmol/mg of protein).
      The opioid agonist-mediated stimulation of [35S]GTP gamma S binding in SH-SY5Y
      cell membranes thus provides a "functional" measure of agonist occupation of mu
      opioid receptors and offers a simple method for the determination of efficacy and
      intrinsic activity of mu-opioid agonists.

PMID- 7723748
TI  - Extracellular ATP stimulates adenylyl cyclase and phospholipase C through
      distinct purinoceptors in NG108-15 cells.
AB  - In neuroblastoma x glioma hybrid NG108-15 cells, ATP induced a concentration
      dependent increase in the intracellular Ca2+ concentration ([Ca2+]i), accompanied
      by inositol phosphate formation. Under the same conditions, we found a marked
      increase in cAMP levels produced by ATP at concentrations similar to those
      required to increase [Ca2+]i. The Ca2+ ionophore A23187 or bradykinin, which
      evoked inositol phosphate formation and increases in [Ca2+]i, did not increase,
      and instead slightly decreased, cAMP content, indicating that ATP-induced cAMP
      accumulation was not due to activation of Ca(2+)-sensitive adenylyl cyclase. The
      effect of ATP on cAMP production was not dependent on generation of adenosine
      caused by ATP hydrolysis. Among several P2 purinoceptor agonists, adenosine-5'-O
      (3-thio)triphosphate, 5'-adenylylimidodiphosphate, and adenosine-5'-O-(2
      thio)diphosphate evoked both cAMP accumulation and Ca2+ mobilization. In
      contrast, beta,gamma-methylene-ATP selectively elicited cAMP accumulation,
      whereas 2-methylthio-ATP and UTP induced only Ca2+ mobilization, without
      affecting cAMP levels. The potent P2x purinoceptor agonist alpha,beta-methylene
      ATP did not induce cAMP accumulation or Ca2+ mobilization. The cAMP accumulation
      induced by ATP was not affected by the P2 receptor antagonist suramin but was
      inhibited by P1 receptor antagonists such as 8-(p-sulfophenyl)theophylline, 3
      isobutyl-1-methylxanthine, and xanthine amine congener. However, the ATP-induced
      increase in [Ca2+]i was not affected by suramin or xanthine amine congener. Taken
      together, these results indicate that ATP activates two distinct purinoceptors
      that are coupled to different signal transduction systems, one being adenylyl
      cyclase and the other phospholipase C, in NG108-15 cells. Furthermore,
      pharmacological profiles of the adenylyl cyclase-coupled receptor were quite
      different from those of any known purinoceptor subtypes, especially in the
      unusual sensitivity of the receptor to P1 and P2 receptor agonists and
      antagonists. It is therefore suggested that ATP-induced cAMP accumulation may be
      mediated by a novel subtype of purinoceptor in NG108-15 cells.

PMID- 7723749
TI  - Unusual carbachol responses in RINm5F cells: evidence for a "distal" site of
      action in stimulus-secretion coupling.
AB  - The mechanisms by which carbachol stimulates insulin release were studied in
      RINm5F cells. Stimulation was associated with mobilization of Ca2+ from
      thapsigargin-sensitive intracellular stores and elevation of the cytosolic Ca2+
      concentration ([Ca2+]i). However, when the elevation of [Ca2+]i was blocked by
      prior treatment of the cells with thapsigargin or with the anticalmodulin agents
      W-7 or W-13, the effect of carbachol to stimulate insulin release was unchanged.
      Thus, the effect of carbachol to increase [Ca2+]i was dissociated from the
      stimulation of release. The role of protein kinase C (PKC) was next investigated.
      Carbachol-stimulated insulin release was unchanged by phorbol ester-induced down
      regulation of PKC, at a time when the stimulation of release by 12-O
      tetradecanoylphorbol-13-acetate was abolished. Similarly, when the effect of 12-O
      tetradecanoylphorbol-13-acetate to stimulate release was blocked by each of three
      separate PKC inhibitors (staurosporine, bisindolylmaleimide, or 1-O-hexadecyl-2-O
      methylglycerol), carbachol stimulated insulin release normally. Thus, the
      carbachol activation of PKC was also dissociated from the stimulation of insulin
      release. Finally, the effect of carbachol was examined in PKC-down-regulated
      cells in the simultaneous presence of thapsigargin. Carbachol still stimulated
      insulin release normally. It is concluded that carbachol stimulates insulin
      release in RINm5F cells by a novel mechanism that does not involve the elevation
      of [Ca2+]i or the activation of PKC. The action of carbachol appears to be
      exerted at a "distal site," beyond the point of increased [Ca2+]i, in stimulus
      secretion coupling.

PMID- 7723750
TI  - Differential activation of human gastrin-releasing peptide receptor-mediated
      responses by bombesin analogs.
AB  - To enable the detailed pharmacological characterization of five bombesin (BN)
      analogs with respect to the human gastrin-releasing peptide (GRP) receptor, we
      ectopically expressed the receptor in BALB/3T3 cells. In such cells (termed GR1
      cells), GRP stimulated DNA synthesis and Ca2+ mobilization. Two of these analogs,
      D-Phe6-BN(6-13) methyl ester (Ki = 1.38 +/- 0.07 nM) and 4-pyridyl-CO-His7-D
      Ala11-Lys12-COCH2CH2-phenyl- BN(7-13) methyl amide (Ki = 2.17 +/- 0.05 nM), were
      pure antagonists of GRP-stimulated DNA synthesis in GR1 cells (IC50 = 14 +/- 8.5
      nM and 5.1 +/- 2.0 nM, respectively), whereas three analogs, Leu13-psi-Leu14-BN
      (Ki = 21.6 +/- 2.2 nM), D-Phe6-BN(6-13) ethyl amide (Ki = 5.17 +/- 0.64 nM), and
      D-Phe6-BN(6-13) propyl amide (Ki = 0.68 +/- 0.01 nM), displayed significant
      partial agonistic activity. Although three analogs promoted mitogenesis in GR1
      cells, none of the analogs stimulated calcium mobilization in GR1 cells. This
      dichotomy was not limited to transfected cells, because the same result was
      obtained for D-Phe6-BN(6-13) propyl amide using human fetal lung cells, which
      naturally express the GRP receptor. We also assessed the effect of BN analogs on
      calcium mobilization in transfected GR9 cells expressing about 30 times higher
      levels of the GRP receptor, compared with GR1 cells. D-Phe6-BN(6-13) ethyl amide,
      D-Phe6-BN(6-13) propyl amide, and Leu13-psi-Leu14-BN were partial agonists of the
      intracellular Ca2+ mobilization response of GR9 cells. One conclusion consistent
      with our data is that GRP-stimulated DNA synthesis requires the activation of far
      fewer receptors than does GRP-stimulated calcium mobilization. Thus, analogs with
      a small amount of agonist activity can trigger a mitogenic response but not an
      intracellular Ca2+ mobilization response, unless cells express a high level of
      receptors. These studies also provide evidence that the promotion of DNA
      synthesis in quiescent GR1 or human fetal lung cells via the GRP receptor does
      not require mobilization of intracellular Ca2+.

PMID- 7723751
TI  - [Use of continuous stacking hybridization in sequencing using modified
      oligonucleotide matrices].
AB  - The opportunity of DNA sequencing by hybridization with oligonucleotide matrix
      (SHOM) with simultaneously use continuous stacking hybridization and gapped
      matrices is considered. The analysis of reconstruction efficiency for various
      combinations matrices and l-oligonucleotides libraries were made. In most cases
      combine use of continuous stacking hybridization and gapped matrices permits to
      decrease the number of additional stacking hybridization twice without lost of
      efficiency.

PMID- 7723752
TI  - [Functional value of 980-1061 sequences of human 18S ribosomal RNA using
      complementary DNA probes].
AB  - Region 980-1061 in human 18S rRNA was chosen on the basis of our previous results
      indicating, that the cross-linking sites of alkylating mRNA analogs are located
      within this region. In the present study, we have used 10 DNA 15-mers
      complementary to various overlapping sequences within the 18S rRNA positions 980
      1061. Their ability to bind selectively at the desired rRNA sequences was proved
      by hydrolysis of 18S rRNA within heteroduplexes with the corresponding probes by
      RNase H. Only four of the probes were able to bind to 40S subunits indicating,
      that the corresponding 18S rRNA sequences 980-994, 987-1001, 1025-1039 and 1032
      1046 are exposed within the subunits. None of the probes inhibited tRNA-dependent
      binding of oligo(U) messengers to 40S subunits. Nevertheless, two probes
      (complementary to 18S rRNA sequences 987-1001 and 1025-1039) being covalently
      attached to 40S subunits, inhibited translation of poly(U) by human 80S ribosomes
      in a cell-free system. The binding of messenger trinucleotide in the complex
      pAUG.40S.Met-tRNA.eIF-2.GTP was strongly affected by the same oligomers. Thus 987
      1001 and 1025-1039 18S rRNA sequences are supposed to be involved in interaction
      with mRNA in the course of translation.

PMID- 7723753
TI  - [A method of automatic determination of "reference" spectra of CD elements of
      circular structure of proteins with the "aromatic contribution"].
AB  - An algorithm (with appropriate application package) which enables automatic
      determination of "reference" CD spectra of different protein secondary structure
      elements from set of CD spectra of proteins with known contents of the elements
      with taking into account of "aromatic contribution" is elaborated. By means of
      these spectra one can determine contents of secondary structure elements in
      arbitrary proteins and polypeptides.

PMID- 7723754
TI  - [Interaction of DNA with actinocyl-bis-thiazole].
AB  - The DNA complexes with actinocyl-bis-bithiazole have been investigated by
      spectrophotometry, viscometry and flow birefringence. It was estimated, that at
      low degrees of binding (r < or = 0.07) this compound binds to DNA by
      bisintercalation via bithiazole groups located in positions 1 and 9 of the
      phenoxazone chromophore. The phenoxazone moiety plays in this case the role of a
      link connecting two intercalating fragments. As r increases, external groove
      binding becomes the second type of complex formation.

PMID- 7723755
TI  - [Dynamic mobility of the histidine-containing domain of spin-labeled lysozyme].
AB  - The hen egg-white lysozyme was modified by the spin label (2,2,6,6
      tetramethylpiperidine-N1-oxyl-4-iodacetamide) at the single histidine residue His
      15. The rotational correlation time of the molecular carrier was found to be
      defined by the mobility of the histidine-bearing domain and not influenced by the
      protein monomer shape at pH 4.7 and dimer shape at pH 7.1. The dependence of
      viscosity at 1 degree C on the distance between outer wide peaks in the
      immobilized EPR spectra enabled us to evaluate rotational correlation time of the
      domain. The molecular mass of the latter was close to the data obtained by X-ray
      analysis. The spin label was highly mobile at room temperature, as the EPR
      spectrum displayed the triple shape; at 1 degree C it was immobilized. The new
      general approach to the EPR spectra simulation was applied to all experimental
      EPR spectra. This approach is based on a substitution of an undefined stochastic
      process of the spin label reorientation relative to the lysozyme domain by the
      defined modelled stochastic processes: axial rotation of the nitroxide relative
      to the preferable axis and angular oscillations of the nitroxide relative to axes
      of the molecular coordinate system. Each of the modelled stochastic processes
      leads to a relative partial averaging of the magnetic tensor components. A set of
      discrete partially averaged states is introduced with the relative cluster of the
      spin-labelled molecules. The resulting EPR spectrum is assumed to be the sum of
      EPR spectra from all the clusters. A good fitting of all simulated EPR spectra is
      obtained.

PMID- 7723756
TI  - [Analytical description of electron-vibrational protein spectra].
AB  - Electron-vibrational spectra of phosphorescence and fluorescence of tryptophan
      residues in proteins at 77 K are best approximated by theoretical curves computed
      according to a model which suggests the existence of two independent series of
      Gaussian vibrational components. Each series contains one type of vibrations.
      Phosphorescence and fluorescence spectra of proteins with various localizations
      of their single tryptophan residue were fitted by a curve computed according to
      this model. The results obtained show that the phosphorescence band of tryptophan
      residues in proteins seems to contain two types of vibrations with frequencies
      650-800 cm-1 and 1350-1500 cm-1. Since the substitution of H2O by D2O does not
      change the frequencies of both vibrations in the phosphorescence spectra of human
      serum albumin, melittin and tryptophan in 1 M KCl, it is reasonable to suggest
      that the 1350-1500 cm-1 series corresponds to the W5 type vibrations (B19a type
      of vibrations of benzene ring). The 650-800 cm-1 series"can be identified with
      W18 type of vibrations (breathing vibrations of indole ring). Phosphorescence
      parameters of tryptophan residues in proteins correlate with their fluorescence
      parameters.

PMID- 7723757
TI  - [Isolation, study of activity, and characteristics of an immunosuppressive liver
      factor causing apoptosis of EL-4 thymoma cells in vitro].
AB  - Immunosuppressive factor (ISFnp) which inhibits proliferation and viability of
      thymoma EL-4 cells was isolated from mouse liver. The testing procedure based on
      the biotransformation of MTT-tetrazolium by mitochondrial enzymes of viable cells
      allowed us to purify this factor as individual peak of protein, that allowed to
      obtain polyclonal rabbit antibodies to this factor. By the methods of double
      immunodiffusion, gel-filtration and SDS-PAGE with subsequent immunoblotting we
      shown that this factor specifically localized in liver and consists two subunits
      of 40 and 42 kDa which form dimers with apparent M(r) about 70-80 kDa. This
      factor induced olygonucleosomal DNA cleavage in EL-4 cells in vitro similar to
      dexamethasone-induced DNA-degradation in thymocytes. This cleavage preceded to
      lysis of EL-4 cells assessed by 51Cr-release, that strongly suggested an
      involvement of apoptosis in cell death mechanism. ISFnp strongly inhibited blast
      transformation and proliferation in MLC-responses to mutant MHC class 2 molecule.
      This effect was not due to deletion of allo-reactive clones, because removing of
      this factor from MLC cultures treated with one for 4 days resulted in blast
      transformation without any reduction of the number of viable cells as well as
      their capacity for secondary responses to the same antigen as compared with
      control cultures.

PMID- 7723758
TI  - [Liquid crystals and liquid crystal dispersions of DNA-daunomycin complexes].
AB  - The X-ray and optical properties as well as the textures of liquid crystals
      formed of DNA molecules bound in complex with an anthracycline antibiotic
      daunomycin were investigated. It was shown that DNA.daunomycin complexes,
      depending on the extent of alteration of the DNA secondary structure by
      daunomycin, could yield two types of cholesterics differing in the direction of
      their spatial twisting as well as nematics. Liquid-crystalline dispersions of
      DNA.daunomycin complexes have CD spectra with "mirror" bands depending on
      daunomycin concentration. "Testing" of the orientation of daunomycin molecules on
      the DNA in liquid-crystalline particles suggested two types of binding.

PMID- 7723759
TI  - [42K protein of shallot X virus is expressed in infected Allium species plants].
AB  - The main difference between genome structures of shallot virus X (ShVX) and
      related potex- and carlaviruses is the unique gene of ShVX coding for a 42K
      protein. The amino acid sequence of this protein was analyzed and compared with
      those of similar proteins from several newly characterised viruses of garlic.
      Using antibodies against the recombinant 42K protein, expression of the 42K
      protein of ShVX was detected in most of plants where the ShVX coat protein is
      present.

PMID- 7723761
TI  - [Heterologous epitopes in the central part of the hepatitis B virus core
      protein].
AB  - A set of plasmids was constructed determining synthesis of hybrid proteins with
      insertions of antigenic determinants of preS1 and preS2 regions of HBV in the
      middle part of HBcAg. The polypeptides containing the 31-36 or monomeric 94-105
      preS1 epitopes were water-soluble and formed particles similar to the 27-nm ones
      of native HBcAg, possessing antigenic properties of both HBcAg and the inserted
      epitope, while the hybrids containing 133-143 of preS2 or a trimeric form of the
      94-105 preS1 epitope became membrane-bound. Another hybrid encoded by plasmid
      pPS2M31 contained two regions of HBcAg modification: insertion of amino acids 133
      143 a.a. (preS2 region) in the N-terminal part and 31-36 (preS1) in the middle
      part of the carrier. The immunogenicity of the epitope inserted into the middle
      part of the HBcAg molecule was an order of magnitude higher than that of the same
      epitope in the N-part of the protein; the fact might be important for
      constructing artificial immunogens.

PMID- 7723760
TI  - [Introduction of heterologous epitopes at the N-terminal part of the hepatitis B
      core protein].
AB  - For investigation of proteins possessing assigned immunological properties,
      plasmids pPS31-42, pPS1-5, pPS2-17, and pPS1P-30 were constructed encoding the
      hepatitis B core protein (HBcAg) with N-terminally inserted immunodominant
      epitopes of preS regions (amino acids 31-36 or 94-105 of preS1, or 133-143 of
      preS2). Analysis of the hybrid proteins with the use of ELISA and immunoelectron
      microscopy showed that the insertions did not prevent specific aggregation of the
      protein molecules, the inserted sequences being exposed on the surface of the
      particles obtained, and both HBcAg and the corresponding preS determinants were
      antigenically active.

PMID- 7723762
TI  - [Cross reactivity and amino acid structural homology of immunodominant peptide
      fragments of structural viruses from the human retroviruses HTLV-I, HTLV-II, HIV
      1, and HIV-2].
AB  - Twelve synthetic peptides corresponding to 9 immunodominant regions of structural
      proteins of human retroviruses HTLV-I, HIV-1, and HIV-2 were studied in enzyme
      linked immunosorbent assay for cross reactivity with heterotypical for each
      peptide anti-retroviral antibodies. The search of amino acid homologies was
      carried using the special computer program followed by the correspondence
      analysis of the discovered homologies and immunodominant fragments. It was found
      that peptides 100-130 p19 gag HTLV-I, 376-392 gp21 env HTLV-I, 381-400 gp21 env
      HTLV-I, 306-328 gp120 env HIV-1, 495-516 gp120 env HIV-1, 584-612 gp41 env HIV-1,
      and 581-603 gp36 env HIV-2 have type-specific reactivity and also cross react
      with 3-54% human sera containing antibodies against heterotypical retroviruses.
      On the other hand, peptides 120-130 p19 gag HTLV-I, 176-201 gp46 env HTLV-I, 291
      312 gp46 env HTLV-I, 330-363 p24 gag HIV-1, and 602-624 gp41 env HIV-1 have shown
      no cross reactive properties; they may be effectively used for type-specific and
      differential serodiagnosis of human retroviral infections.

PMID- 7723763
TI  - [Molecular interactions during fibrinolysis. Search for new plasminogen
      activators].
AB  - The data on the kinetics of plasminogen activation by its tissue and urokinase
      type plasminogen activators are reviewed. The mechanisms of this interaction in
      the presence of fibrin are analyzed. The regulatory role of fibrin in plasminogen
      activation involving its direct interaction with tissue-type plasminogen
      activator and indirect interaction with urokinase-type plasminogen activator is
      demonstrated. The functions of these activators in fibrinolysis as well as
      clinical and experimental data demonstrating their mutual contribution to
      thrombus elimination were revealed. The criteria of thrombolytic efficacy of
      plasminogen activators were defined, and the data on fibrinolytic preparations
      obtained by chemical modification, recombinant DNA techniques, or their
      combination were analyzed from this standpoint. The prospects for the development
      of new-generation plasminogen activators and the importance of studying the
      properties of thrombolytic compositions were demonstrated. The results of
      molecular, physiological, and clinical studies concerning the therapy with
      plasminogen activators are considered.

PMID- 7723764
TI  - [Effect of on various cell lines of p53 cDNA, expressed under the control of an
      exogenous homologous promotor].
AB  - Previous studies indicate that the wild-type p53 (unlike its mutant forms present
      in tumor cells) possesses growth suppressor activity specific for transformed
      cells. However, recombinant p53 gene governed by strong heterologous promoters
      was used in most of these experiments, that resulting in overexpression of p53.
      In order to create more physiologically adequate system, we placed the wild-type
      p53 gene and the His273 mutant under control of homologous p53 gene promoter
      within self- inactivating retroviral vector. Recombinant viral stocks were used
      to infect LIM1215, SW480, A431, 293, HeLa and K562 cell lines. These cell lines
      were found to be highly sensitive to the wild-type p53. The only cell line
      (LIM1215), that produced few viable colonies expressing wild-type p53, initially
      contained in its genome two unmodified alleles of the p53 gene. For the cell line
      HeLa initial proliferation of resistant colonies was observed, however, after a
      week, the cells stopped to divide and died due to apoptosis. Expression of the
      mutant (His273) p53 was tolerated by most cell lines, although in HeLa cells the
      doubling time and density of confluent culture were slightly reduced. These cells
      become more dependent on serum and factors from the culture medium, contrary ti
      the cell lines SW480 and A431 expressing His273 p53.

PMID- 7723765
TI  - [Methylation of the factor IX gene--a basic reason for the mutation causing
      hemophilia B].
AB  - The analysis of 750 mutations in the gene of blood coagulation factor IX has been
      made for 806 patients with haemophilia B. It has been found that 40% of all point
      mutations take place in 11 "hot spots", i.e., methylated CG sites, and are CG-
      >TG or CA transitions. Mechanism proposed explains the high rate of these
      transitions by m5C deamination during replicative DNA methylation and by mistakes
      of G/T-repair. This is why mutations constantly occur de novo in the factor IX
      gene, and haemophilia B maintains on a high level. Asymmetry of C-->T and G-->A
      transitions is found in some CG sites at different DNA chains, and is related to
      occurring "missense" mutations, which usually escape from the detection. Summing
      up these substitutions, CG methylation of the factor IX gene contributes to 50%
      of all point mutations. Thus, mutations in the CG sites take place in overall 48
      times more frequently than in other sites of the gene. It has been found that at
      least 35 new CG sites are a result of sporadic mutations, and methylation and
      mutations of these sites may cause 14% of substitutions in the factor IX gene.
      The "hot spots" for T-->C transitions in codon of Ile397 can be a result both of
      "founder effect" and of recessive mutations in such CG site in mother's parents.
      It is shown that methylated CTCG sites, as well as G/T-repair mistakes, can be
      potential sources of 5.4% of mutations in the gene. Thus, from 50 to 70% of all
      mutations may be the result of the gene methylation in human genome. The analysis
      of duplex frequencies in the factor IX gene has shown that the loss of 60 CG
      sites and the accumulation of 8% of mutations may be a result of "fossil" CG
      methylation. The remained 20 CG sites are located in the codons of those amino
      acids which positions are more critical for the factor IX activity. It has been
      proposed that the most radical way in haemophilia B therapy can be a protection
      of the factor IX gene from methylation in the human genome.

PMID- 7723766
TI  - [Use of markers for selecting recombinant vaccinia viruses].
AB  - The use of selected and nonselected markers for obtaining vaccinia virus
      recombinants is examined. The advantages of various selection systems are
      discussed.

PMID- 7723767
TI  - [Stability of phosphodiester tRNA bonds lacking minor nucleosides, in aminoacyl
      tRNA-synthetase complexes].
AB  - The stability of phosphodiester bonds in tRNA(Trp) (E. coli, bovine) and
      tRNA(Phe) (yeast) synthesized in vitro was studied in the complexes with cognate
      aminoacyl-tRNA synthetases. In contrast to E. coli tRNA(Gln) where synthetase
      induced cleavage has been reported, we have failed to observe this effect with
      tRNA(Trp) and tRNA(Phe). Consequently, the weakness of sugar-phosphate backbone
      of tRNA-transcripts in the complexes is not a common feature for all tRNA
      synthetase pairs. The cleavage mechanism in the case of tRNA(Gln) remains
      obscure.

PMID- 7723768
TI  - [A normalized cDNA library from human erythroleukemia cells].
AB  - Normalized cDNA library from human erythroleukemia cells has been constructed.
      For equalizing frequencies of different cDNAs denaturation was carried out
      followed by partial reassociation. Single-stranded cDNAs separated by
      hydroxyapatite chromatography were transformed into double-stranded form by PCR
      and cloned in lambda gt11. Frequencies of 10 control nucleotide sequences were
      estimated. After normalization frequencies of the abundant sequences decreased.
      The normalized cDNA library may be used for search of the clones corresponding to
      the rare mRNAs and for human genome mapping.

PMID- 7723769
TI  - Spontaneous and cycloheximide-induced interleukin-10 mRNA expression in human
      mononuclear cells.
AB  - Interleukin-10 (IL-10) is known to be spontaneously produced by human peripheral
      blood mononuclear cells. In order to define the cell type in which IL-10 gene is
      spontaneously expressed we used the reverse polymerase chain reaction for IL-10
      mRNA expression, which was also used to study the effects of cycloheximide (CHX).
      First, we found that IL-10 mRNA is spontaneously expressed in monocytes and B
      cells but not T cells from healthy donors, and second, we demonstrated that CHX
      superinduces IL-10 mRNA in monocytes and B cells. Experiments including nuclear
      run-on analyses established that the effects of CHX on IL-10 gene expression
      involve both gene transcription and mRNA stabilization.

PMID- 7723770
TI  - Preparation and characterization of a disulfide-stabilized Fv fragment of the
      anti-Tac antibody: comparison with its single-chain analog.
AB  - Recombinant DNA techniques now allow the production of "mini-antibodies" called
      Fv fragments. These have been produced either as the independent variable domains
      of the heavy and light chains non-covalently associated in one-to-one
      stoichiometry or as single-chain gene products with the two domains linked by an
      intervening peptide sequence. Although Fv fragments can have excellent binding
      properties, they are often difficult to produce in good yield and lack the
      characteristic stability of whole antibodies. To improve the stability of the Fv
      molecule, we have introduced a cysteine residue into conserved framework regions
      of both the heavy and light variable domains from the anti-Tac antibody at
      positions compatible with the formation of an interdomain disulfide linkage (i.e.
      VH-44 and VL-99). The mutant subunits form a disulfide-bonded Fv molecule, which
      binds to the alpha-subunit of the IL2 receptor (IL2R alpha) with an affinity
      identical to that of humanized anti-Tac IgG. This disulfide-stabilized Fv (dsFv)
      proved to be substantially more resistant to denaturation by heat or urea
      treatment than the single-chain Fv (scFv). Furthermore, the yield of dsFv is 
      four-fold higher than that of the single-chain analog.

PMID- 7723771
TI  - Non-specific cross-reactivity of hydrophobic serum IgE to hydrophobic drugs.
AB  - The purpose of this work was to study the involvement of serum hydrophobic IgE in
      non-specific cross-reactions with hydrophobic drugs such as cyclohexenyl
      derivatives. Hydrophobic IgE were detected by radioimmunoassay. The results were
      expressed as the percentage of labelled anti-IgE which were adsorbed to the drug
      solid phase via IgE of the patient serum. Phenyl-Sepharose IgE-RIA was at 4.6 +/-
      0.7%, 125 +/- 6.5% and 17.8 +/- 8.9% in control subjects (n = 24), in atopic
      patients with positive Phadiatop (n = 30) and in patients with drug allergy (n =
      23), respectively. We selected five patients who were allergic to either
      penicillin, propofol, glafenin or paracetamol and who had a Phenyl-Sepharose IgE
      RIA greater than 20%. In these five cases, IgE-RIA were positive (percentage at
      least twice more than that obtained with control sera) with all the solid phases
      prepared with hydrophobic drugs such as penicillin, propofol, glafenin,
      paracetamol and mexiletine. Inhibition of IgE binding by monoethylene-glycol
      showed that the cross-reactivity was due to hydrophobic binding of IgE to the
      drug. Three of the five patients were allergic to penicillin and underwent on
      adverse reaction against another cyclohexenyl derivative, namely propofol and
      glafenin. In conclusion, we have observed the presence of 'hydrophobic IgE (with
      positive Phenyl-Sepharose RIA)' in 64% of patients allergic to a hydrophobic
      drug.

PMID- 7723772
TI  - Class I MHC alpha 3 domain can function as an independent structural unit to bind
      CD8 alpha.
AB  - Functional interactions between CD8-dependent cytotoxic T cells and their targets
      require physical contact between CD8 and a non-polymorphic determinant on the
      alpha 3 domain of the class I MHC molecule. We developed a cell-free assay to
      directly monitor this molecular interaction, specifically excluding the
      participation of other cellular proteins and lipids. This assay employed a
      soluble CD8 derivative and a plate-bound HLA-A2.1 derivative, alpha 3/MalE, in
      which the alpha 3 domain has been expressed independently of its neighboring
      polypeptide domains on the native class I MHC molecule and beta 2-microglobulin
      (beta 2-m). These proteins were produced using eukaryotic and prokaryotic
      expression systems, respectively. Our data demonstrated specific, saturable
      binding between soluble CD8 alpha (sCD8 alpha) and alpha 3/MalE, and the Kd of
      this interaction was determined to be 4.5 x 10(-7) M. Monoclonal antibodies (mAb)
      directed against either CD8 or the alpha 3 domain of class I MHC inhibited
      binding; mAb directed against other sites on class I MHC and beta 2-m did not.
      Our data suggest that the interaction between CD8 alpha and the alpha 3 domain of
      class I MHC does not require the participation of neighboring class I sequences
      or beta 2-m.

PMID- 7723773
TI  - Alternative processing of IgA pre-mRNA responds like IgM to alterations in the
      efficiency of the competing splice and cleavage-polyadenylation reactions.
AB  - Both the membrane-associated and -secreted Ig proteins are encoded by a single
      gene whose primary transcript is alternatively processed at its 3' end. The
      relative use of the alternative processing pathways is regulated during B cell
      maturation. This alternative RNA processing involves two competing reactions,
      splicing from the last constant region exon to the membrane exon(s) and cleavage
      polyadenylation at the secretory-specific poly(A) site. Studies with the IgM
      encoding mu gene have shown that cell-specific regulation requires that the
      efficiencies of these two reactions be balanced; any gene modifications that
      substantially improve or reduce the efficiency of either reaction also abrogate
      the regulatory shift in alternative processing pathways. All of the Ig isotypes
      that undergo a membrane-to-secreted switch during B cell maturation have a
      similar gene structure, thus suggesting that they might all be regulated by the
      same mechanism. We show that RNA processing of chimeric mu alpha genes containing
      modifications in the C alpha 3 exon size and the C alpha 3-alpha m intron size
      respond to these modifications as predicted by previous mu gene studies. In
      addition, RNA expression ratios from the chimeric mu alpha genes are regulated in
      B cells and plasma cells. This provides good evidence that splicing and cleavage
      polyadenylation in the alpha gene are balanced reactions that are regulated in
      the same way as in the mu gene.

PMID- 7723774
TI  - Enhanced immunoreactivity and preferential heterodimer formation of reassociated
      Fel d I recombinant chains.
AB  - In this study we have addressed the question of whether reassociating the two
      recombinant protein chains that comprise the major cat dander allergen, Fel d I,
      would change the overall IgE and allergic patient T cell immunoreactivity
      compared to the native molecule. To accomplish this, the chains were combined
      under reducing and denaturing conditions, then allowed to reassociate by dilution
      and extensive dialysis against a physiological buffer. An initial examination of
      the reaction products using quantitative capture ELISA demonstrated comparable
      reactivity to Fel d I. Further analysis, using a pool of cat allergic patient
      plasma, showed that the products of the reassociation reaction (rFel d I) also
      possessed an enhanced IgE binding capacity. Depletion ELISA results gave only a
      5% difference in reactivity between rFel d I and the native protein versus a 20%
      difference with the mixture of the two chains. Comparative secondary T cell
      stimulation assays were subsequently performed using cat allergic patient
      peripheral blood lymphocytes. Here the results demonstrated no loss of reactivity
      with the reassociated chains as compared to Fel d I or the two mixed recombinant
      chains. To biochemically characterize the products of the reassociation reaction
      we have performed reverse phase HPLC and then analysed the isolated fractions by
      mass spectrometry. It was clear from these results that like the native Fel d I,
      the products of the reassociation reaction favored heterodimer formation, with no
      homodimer being detected. This implies that the reassociated protein chains had
      preferentially adopted a native-like conformation.

PMID- 7723775
TI  - Mapping of the antigenic and allergenic epitopes of Lol p VB using gene
      fragmentation.
AB  - The recombinant proteins of Lol p VA and Lol p VB expressed in E. coli reacted
      with IgE antibodies from sera of allergic patients and mAbs FMC A7 and PpV1.
      Cross-absorption analyses using these recombinant proteins showed that Lol p VA
      and Lol p VB possess both similar and unique IgE binding determinants. Gene
      fragmentation was utilized to localize the antigenic and allergenic determinants
      of Lol p VB. When full-length cDNA of Lol p VB was digested into three fragments
      and expressed as the fusions from the glutathione transferase of pGEX vectors,
      fragments Met1-Val196 and Asp197-Val339 bound IgE while fragment Met1-Pro96 did
      not. The data suggest that there are at least two IgE binding determinants in Lol
      p VB. In addition, only fragment Met1-Val196 reacted with mAb PpV1. The
      localization of these determinants was further resolved using random fragment
      expression libraries. The mAb PpV1 determinant was near the N-terminal region of
      Lol p VB molecule. The IgE binding determinants were distributed in the central
      region: region I (amino acids 111-195) and II (199-254). These IgE binding
      determinants are conserved in Lol p VA.

PMID- 7723776
TI  - Conservation among Old World Leishmania species of six physical linkage groups
      defined in Leishmania infantum small chromosomes.
AB  - We have characterised 49 DNA probes specific for each of the six smallest
      chromosomes in Leishmania infantum and have examined the allocation of these
      probes in the molecular karyotypes of the other Old World Leishmania species
      Leishmania donovani, Leishmania major, Leishmania tropica and Leishmania
      aethiopica. These 49 probes define 6 physical linkage groups in the molecular
      karyotypes of various strains of L. infantum. 40 of these probes hybridise in the
      other Old World Leishmania species and show a remarkably conserved linkage
      pattern. No interchromosomal exchange nor fusion could be detected. Thus, in
      spite of the chromosomal size polymorphisms, the general structure of the genome
      seems to be conserved in the six smallest chromosomes among Old World Leishmania
      species. This structural genomic homogeneity should be helpful for mapping
      studies of any Old World Leishmania genomes.

PMID- 7723777
TI  - A successful backcross in Trypanosoma brucei.
AB  - Genetic exchange can take place between different strains of Trypanosoma brucei
      ssp. when they are cotransmitted via the tsetse fly vector, but the mechanism and
      limits of compatibility between strains are ill-defined as yet. Following the
      recovery of several hybrid genotypes with single drug resistance from a cross of
      drug resistant parental strains, we attempted a series of backcrosses and F1
      crosses, selecting hybrids by double drug resistance. Of 4 backcrosses, one
      produced hybrid progeny, the analysis of which is presented here, but none of the
      4 F1 crosses produced hybrid progeny. However, among experimental flies from the
      8 crosses, although there were large numbers of salivary gland infections, very
      few consisted of a mixture of parental clones, a prerequisite for mating. In the
      successful backcross both parents were diploid, but none of the crosses involving
      triploid clones produced hybrid progeny. The hybrid-secreting fly from the
      backcross contained a mixture of hybrid and parental clones. The hybrid clones
      had approximately 3n DNA contents relative to the 2n parental clones and fell
      into 2 groups with respect to restriction site polymorphisms in kinetoplast DNA
      maxi-circles. Fingerprinting by random PCR amplification using 8 different
      arbitrary primers showed minor variation between the hybrid clones.

PMID- 7723778
TI  - The sequence of Plasmodium falciparum histone H3.

PMID- 7723779
TI  - Minimal variation in the transmission-blocking vaccine candidate Pfs48/45 of the
      human malaria parasite Plasmodium falciparum.

PMID- 7723780
TI  - The primary structure of an Entamoeba histolytica enolase.

PMID- 7723781
TI  - Specific DNA polymorphisms discriminate between virulence and non-virulence to
      mice in nine Toxoplasma gondii strains.

PMID- 7723782
TI  - Cloning and characterization of a cDNA encoding the catalytic subunit of a cAMP
      dependent protein kinase from Ancylostoma caninum third-stage infective larvae.

PMID- 7723783
TI  - A homologue of the nuclear GTPase ran/TC4 from Trypanosoma brucei.

PMID- 7723784
TI  - Point mutations in the dihydrofolate reductase-thymidylate synthase gene and
      pyrimethamine and cycloguanil resistance in Plasmodium falciparum.

PMID- 7723785
TI  - Mechanism of regulation of malarial invasion by extraerythrocytic ligands.
AB  - Invasion of red cells by Plasmodium falciparum in vitro was inhibited by a range
      of extracellular ligands, none of which block the major receptors for merozoites.
      Most effective, in terms of dose response, were two monoclonal antibodies against
      the Wrb antigen on glycophorin A; wheat germ agglutinin which also binds to
      glycophorin, and an anti-band 3 monoclonal antibody, caused inhibition of
      invasion at higher levels of saturation, while concanavalin A, which binds to
      band 3, was without effect. All the ligands except concanavalin A, increased the
      rigidity of the host cell membrane. The anti-Wrb antibodies generated the highest
      dose response effect, but no correlation between invasion and shear elastic
      modulus of the membrane could be established. All ligands, with the exception of
      concanavalin A, caused a reduction in the translationally mobile fractions of
      band 3 and glycophorin, as revealed by fluorescence recovery after photobleaching
      (FRAP). Invasion diminished with loss of mobile band 3, engendered by bound wheat
      germ agglutinin or anti-band 3, falling precipitately when the mobile fraction
      fell below 40% of that in unperturbed membranes. Both anti-Wrb antibodies
      suppressed invasion completely at concentrations insufficient to affect
      significantly either membrane rigidity or intramembrane protein diffusion. A
      univalent anti-glycophorin A (Fab) fragment, the parent antibody of which was
      previously shown to inhibit invasion strongly, had only a modest effect on
      invasion and induced a correspondingly small change in the mobile fraction of
      band 3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723786
TI  - Activity, pharmacological inhibition and biological regulation of 3-hydroxy-3
      methylglutaryl coenzyme A reductase in Trypanosoma brucei.
AB  - Activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the key enzyme
      in the biosynthesis of steroids and polyisoprenoids in mammalian cells, has been
      detected in both the bloodstream form and the culture-adapted procyclic form of
      Trypanosoma brucei (3.7 +/- 0.6 and 12.7 +/- 1.8 pmol mevalonate produced min-1
      (mg cell protein)-1, respectively). The enzyme activity is enriched 6-fold in
      microsomal fractions. Several competitive inhibitors of mammalian HMG-CoA
      reductase, including synvinolin (simvastatin), inhibit the multiplication of both
      forms of trypanosome in vitro (IC50, approx. 25-50 microM after 2-3 days). This
      growth inhibition is potentiated by agents interfering with the exogenous supply
      of cholesterol, such as antibodies blocking the low-density lipoprotein (LDL)
      receptor, or 5 microM chloroquine. Conversely, growth inhibition by synvinolin
      can be largely reverted either by 300 nM LDL or by products of the mevalonate
      pathway, such as 20 mM mevalonate and in procyclics by 100 microM squalene or
      cholesterol. In procyclics, low concentrations of synvinolin selectively inhibit
      the incorporation of [14C]acetate into sterols, but not into fatty acids. These
      results argue for a critical role in trypanosomes of a mevalonate pathway, that
      is involved in the biosynthesis of sterol and probably of other metabolites. The
      HMG-CoA reductase activity is decreased 2-fold in procyclics incubated with 4 mM
      mevalonate and increased 2-fold in the presence of 2.5 microM synvinolin.
      Synvinolin also upregulates LDL binding up to 4-fold. These data suggest that HMG
      CoA reductase and LDL receptor expression are regulated in T. brucei as in
      mammalian cells, to ensure sterol homeostasis.

PMID- 7723787
TI  - Yeast artificial chromosome (YAC)-based genome mapping of Schistosoma mansoni.
AB  - Schistosoma mansoni has 7 pairs of autosomal chromosomes and one pair of sex
      chromosomes (ZZ for a male worm and ZW for a female), of a haploid genome size of
      2.7 x 10(8) bp. We initiated the molecular genetic approach for the detailed
      characterization and understanding of the evolutionary biology of schistosomes.
      We have constructed a yeast artificial chromosome (YAC)-library with partially
      digested parasite genomic DNA, and the chromosome location of each insert was
      detected by fluorescent in situ hybridization (FISH). The library contains > 2283
      clones with an average insert size of 358 kb, which represents a 2.6-fold
      coverage of the genome (> 7.2 x 10(8) bp). 100 randomly selected YAC clones were
      localized by FISH and found to be distributed widely among all chromosomes. The
      assembly of 14 YACs distributed almost the whole region of chromosome 3.
      Generated expressed sequenced tags (ESTs) derived from a unidirectional cDNA
      library were also used for further characterization of the YAC inserts. These
      results indicate that an extensive contig assembly of the entire chromosomes and
      a reasonably detailed gene map should be feasible in the near future.

PMID- 7723788
TI  - Genomic organization of an invariant surface glycoprotein gene family of
      Trypanosoma brucei.
AB  - The genomic organization of a gene family for the invariant surface glycoprotein,
      ISG75 (invariant surface glycoprotein with a molecular mass of 75 kDa), from
      Trypanosoma brucei is described. In T. brucei strain 427 ISG75 genes are present
      in tandem arrays at two loci, A and B, containing 5 and 2 copies, respectively.
      At the 3'-end of locus A, a single gene was identified that encodes a structural
      isoform of ISG75. This isoform contains a unique amino-terminal domain, whereas
      the rest of the protein is nearly identical to the polypeptides encoded by the
      other genes. This isoform is transcribed into a stable mRNA, but the expression
      of the derived polypeptide was below the detection limit. The ISG75 gene clusters
      are present on chromosomal bands 9' and 10, supporting the hypothesis of
      Gottesdiener et al. [25] that these bands contain allelic chromosomes. The total
      number of ISG75 genes is strain dependent, but at least one copy of the unique
      isoform is present in every variant tested.

PMID- 7723789
TI  - A genetic locus on Plasmodium falciparum chromosome 12 linked to a defect in
      mosquito-infectivity and male gametogenesis.
AB  - Infection of mosquitoes by Plasmodium spp. requires sexual differentiation of the
      malarial parasite in the vertebrate host and mating of the heterogametes in the
      vector midgut. A Plasmodium falciparum clone, Dd2, differentiates into normal
      appearing gametocytes, yet poorly infects mosquitoes. The Dd2 clone, however,
      effectively cross-fertilized HB3, a Central American P. falciparum clone, and
      yielded several independent recombinant progeny. We have examined 11 HB3 x Dd2
      progeny for their ability to infect mosquitoes and to differentiate into male
      gametes. Our analyses indicate that the poor mosquito-infectivity of the Dd2
      clone results from a defect in male gametogenesis. This defect was inherited as a
      single locus in the independent recombinant progeny of HB3 x Dd2. Comparison with
      a restriction fragment length polymorphism map of the HB3 x Dd2 cross indicates
      that the defective phenotype of Dd2 maps to a locus on P. falciparum chromosome
      12. This genetic locus may contain determinants that play a crucial role in male
      gametogenesis by P. falciparum.

PMID- 7723790
TI  - The presence of galactofuranose and ribose units in asparagine-linked
      oligosaccharides of the digenetic trypanosomatid Endotrypanum schaudinni.
AB  - It was found that the digenetic trypanosomatid Endotrypanum schaudinni
      transferred Man7GlcNAc2 in protein N-glycosylation. Endo-beta-N
      acetylglucosaminidase H-sensitive oligosaccharides were identified as
      Man7GlcNAc2, Man6GlcNAc2, Rib1Man6GlcNAc2 and/or Gal1Man6GlcNAc2, Man5GlcNAc
      containing two galactose or ribose units or one of each residues, Rib1Man5GlcNAc2
      and Gal1Man5GlcNAc2. The galactoses were in the furanose configuration. Endo-beta
      N-acetylglucosaminidase H-resistant glycopeptides that were retained by
      concanavalin A-Sepharose and eluted with alpha-methylmannoside were found to
      contain mannose, galactofuranose and ribose units. The presence of
      galactofuranoses in N-glycoproteins has been reported previously in several
      monogenetic trypanosomatids but only in one digenetic parasite (Trypanosoma
      cruzi). This and a recent publication on the structure of Blastocrithidia culicis
      N-linked oligosaccharides are the first reports on the presence of ribose in
      eukaryotic glycoconjugates.

PMID- 7723791
TI  - Chemical characterisation of glycosylinositolphospholipids of Herpetomonas
      samuelpessoai.
AB  - The structure of two glycosylinositolphospholipids of the cell surface of the
      monoxenic protozoan Herpetomonas samuelpessoai have been deduced by methylation
      analysis, fast-atom bombardment mass spectrometry and two dimensional nuclear
      magnetic resonance spectroscopy. These glycolipids have features in common with
      the glycoinositolphospholipids of both Leishmania and Trypanosoma cruzi,
      resembling the former by the presence of the hybrid type core sequence Man alpha
      1-->3(Man alpha 1-->6)Man alpha 1-->4GlcN alpha 1-->6 myo-inositol-1-PO4-lipid,
      while the 2-aminoethylphosphonate substituent on 0-6 of glucosamine and the
      presence of ceramide in place of glycerol lipids is more reminiscent of T. cruzi.
      Possible phylogenetic implications of these observations are discussed.

PMID- 7723792
TI  - Reconstitution of the trypanolytic factor from components of a subspecies of
      human high-density lipoproteins.
AB  - Trypanosoma brucei brucei is non-infectious to man due to the sensitivity of
      these parasites to the lytic activity of normal human serum. Apolipoproteins
      (apo) have been purified, under non-denaturing conditions, from the subclass of
      human high-density lipoprotein (HDL), termed trypanosome lytic factor (TLF),
      which is responsible for the cytotoxicity of human serum to T. b. brucei. The TLF
      apolipoproteins were purified by anion exchange chromatography in the presence of
      the nonionic detergent octylglucoside and a reconstitution method was developed
      which allowed the role of the individual apolipoproteins and different lipids to
      be assessed. The results suggest that the TLF lipids do not have a direct role in
      lysis but are necessary for the correct assembly of the lytic HDL particle. Apo A
      I, apo L-III and apo L-I contribute to lysis in reconstituted particles but
      individually they are not cytotoxic. Apo A-II was not required in the
      reconstituted TLF particle for trypanosome lysis. Formation of a lytic HDL
      particle required apo L-III suggesting its potential role as a toxin. Thermal
      inactivation of TLF activity correlated with the amount of denatured apo L-I,
      indicating that apo L-I was involved in lysis of T. b. brucei by native TLF.

PMID- 7723793
TI  - Characterization of a species-specific satellite DNA from the entomopathogenic
      nematode Steinernema carpocapsae.
AB  - An HaeIII satellite DNA family has been cloned from the entomopathogenic nematode
      Steinernema carpocapsae. This repeated sequence appears to be an unusually
      abundant satellite DNA, since it constitutes about 62% of the S. carpocapsae
      genome. The nucleotide sequences of 13 monomers have been determined. This
      satellite DNA family is represented by two sub-families: one with monomeric units
      of 170 bp and the other with monomeric units of 182 bp. These monomers are quite
      homogeneous in sequence, showing an average intermonomer variability of 6% from
      the consensus sequence. These results suggest that some homogenizing mechanism is
      acting to maintain the homogeneity of this satellite DNA. After hybridization
      with the genomic DNA of several other Steinernema species, this DNA sequence
      appears to be specific to the S. carpocapsae genome. Therefore, the species
      specificity and the high copy number of the HaeIII satellite DNA sequence should
      provide a rapid and powerful tool which could contribute to the identification of
      Steinernema species.

PMID- 7723794
TI  - Mutation of the androgen-receptor gene in metastatic androgen-independent
      prostate cancer.
AB  - BACKGROUND: Metastatic prostate cancer is a leading cause of cancer-related death
      in men. The rate of response to androgen ablation is high, but most patients
      relapse as a result of the outgrowth of androgen-independent tumor cells. The
      androgen receptor, which binds testosterone and stimulates the transcription of
      androgen-responsive genes, regulates the growth of prostate cells. We analyzed
      the androgen-receptor genes from samples of metastatic androgen-independent
      prostate cancers to determine whether mutations in the gene have a role in
      androgen independence. METHODS: Complementary DNA was synthesized from metastatic
      prostate cancers in 10 patients with androgen-independent prostate cancer, and
      the expression of the androgen-receptor gene was estimated by amplification with
      the polymerase chain reaction. Exons B through H of the gene were cloned, and
      mutations were identified by DNA sequencing. The functional effects of the
      mutations were assessed in cells transfected with mutant genes. RESULTS: All
      androgen-independent tumors expressed high levels of androgen-receptor gene
      transcripts, relative to the levels expressed by an androgen-independent prostate
      cancer cell line (LNCaP). Point mutations in the androgen-receptor gene were
      identified in metastatic cells from 5 of the 10 patients examined. One mutation
      was in the same codon as the mutation found previously in the androgen
      independent prostate-cancer cell line. The mutations were not detected in the
      primary tumors from of the two patients. Functional studies of two of the mutant
      androgen receptors demonstrated that they could be activated by progesterone and
      estrogen. CONCLUSIONS: Most metastatic androgen-independent prostate cancers
      express high levels of androgen-receptor gene transcripts. Mutations in androgen
      receptor genes are not uncommon and may provide a selective growth advantage
      after androgen ablation.

PMID- 7723795
TI  - Indicators of life-threatening malaria in African children.
AB  - BACKGROUND: About 90 percent of the deaths from malaria are in African children,
      but criteria to guide the recognition and management of severe malaria have not
      been validated in them. METHODS: We conducted a prospective study of all children
      admitted to the pediatric ward of a Kenyan district hospital with a primary
      diagnosis of malaria. We calculated the frequency and mortality rate for each of
      the clinical and laboratory criteria in the current World Health Organization
      (WHO) definition of severe malaria, and then used logistic-regression analysis to
      identify the variables with the greatest prognostic value. RESULTS: We studied
      1844 children (mean age, 26.4 months) with a primary diagnosis of malaria. Not
      included were 18 children who died on arrival and 4 who died of other causes. The
      mortality rate was 3.5 percent (95 percent confidence interval, 2.7 to 4.3
      percent), and 84 percent of the deaths occurred within 24 hours of admission.
      Logistic-regression analysis identified four key prognostic indicators: impaired
      consciousness (relative risk, 3.3; 95 percent confidence interval, 1.6 to 7.0),
      respiratory distress (relative risk, 3.9; 95 percent confidence interval, 2.0 to
      7.7), hypoglycemia (relative risk, 3.3; 95 percent confidence interval, 1.6 to
      6.7), and jaundice (relative risk, 2.6; 95 percent confidence interval, 1.1 to
      6.3). Of the 64 children who died, 54 were among those with impaired
      consciousness (n = 336; case fatality rate, 11.9 percent) or respiratory distress
      (n = 251; case fatality rate, 13.9 percent), or both. Hence, this simple bedside
      index identified 84.4 percent of the fatal cases, as compared with the 79.7
      percent identified by the current WHO criteria. CONCLUSIONS: In African children
      with malaria, the presence of impaired consciousness or respiratory distress can
      identify those at high risk for death.

PMID- 7723796
TI  - Suppression of retinoic acid receptor-beta in premalignant oral lesions and its
      up-regulation by isotretinoin.
AB  - BACKGROUND: Retinoids are effective in the treatment and prevention of certain
      human cancers. Most of their actions are thought to result from changes in gene
      expression mediated by nuclear retinoic acid receptors and retinoid X receptors.
      We conducted a study to determine whether the expression of these receptors was
      altered in premalignant oral lesions and, if so, whether their expression could
      be restored by treatment with isotretinoin. METHODS: We performed in situ
      hybridization of retinoic acid receptors and retinoid X receptors using antisense
      riboprobes in specimens of oral mucosa from 7 normal subjects and specimens of
      premalignant oral lesions from 52 patients before treatment with isotretinoin and
      from 39 of the 52 patients after three months of treatment. RESULTS: All the
      normal specimens expressed retinoic acid receptor-beta messenger RNA (mRNA). In
      contrast, retinoic acid receptor-beta mRNA was detected in only 21 of the 52
      premalignant oral lesions (P = 0.003). Thirty-five of the 39 specimens available
      for evaluation after treatment expressed retinoic acid receptor-beta mRNA (P <
      0.001). All normal and premalignant specimens expressed similar levels of mRNA
      for retinoic acid receptor-alpha and retinoic acid receptor-gamma and the three
      types of retinoic X receptors, alpha, beta, and gamma. The levels of retinoic
      acid receptor-beta mRNA increased in the specimens from 18 of the 22 patients who
      had responses to isotretinoin and in 8 of the 17 specimens from the patients
      without responses (P = 0.04). CONCLUSIONS: The expression of retinoic acid
      receptor-beta mRNA is selectively lost in premalignant oral lesions and can be
      restored by treatment with isotretinoin. Restoration of the expression of
      retinoic acid receptor-beta mRNA is associated with a clinical response. Retinoic
      acid receptor-beta may have a role in mediating the response to retinoids and may
      be a useful intermediate biologic marker in trials of these agents for the
      prevention of oral carcinogenesis.

PMID- 7723797
TI  - Fertility in men exposed prenatally to diethylstilbestrol.
AB  - BACKGROUND: Prenatal exposure to diethylstilbestrol causes infertility in male
      mice and has been associated with malformations of the genital tract in men.
      However, little is known about the fertility of men who have been exposed
      prenatally to diethylstilbestrol. METHODS: In 1950 through 1952, 1646 pregnant
      women were enrolled in a randomized, placebo-controlled clinical trial of
      diethylstilbestrol at Chicago Lying-in Hospital. We interviewed men who were born
      to the women during that study about their fertility. RESULTS: Four decades after
      their birth, we were able to trace 548 of the surviving sons (68 percent). Ninety
      percent consented to be interviewed (253 who had been exposed to
      diethylstilbestrol in utero and 241 who had not been exposed). Congenital
      malformations of the genitalia were reported three times as often by the
      diethylstilbestrol-exposed men as by the sons of the women in the placebo group.
      Within the exposed group, malformations were reported twice as often among those
      exposed to diethylstilbestrol before the 11th week of gestation as among those
      exposed later (P = 0.05). Men with genital malformations were nonetheless as
      fertile as other men. The diethylstilbestrol-exposed men (with or without genital
      malformations) had no impairment of fertility by any measure, including whether
      they had ever impregnated a women, age at the birth of their first child, average
      number of children, medical diagnosis of a fertility problem, or length of time
      to conception in the most recent pregnancy of the female partner. Finally,
      diethylstilbestrol-exposed men had no impairment of sexual function, as
      indicated, for example, by the frequency of intercourse or reported episodes of
      decreased libido. CONCLUSIONS: High doses of diethylstilbestrol did not lead to
      impairment of fertility or sexual function in adult men who had been exposed to
      the drug in utero.

PMID- 7723798
TI  - Images in clinical medicine. Ehrlichiosis.

PMID- 7723800
TI  - Child abuse and neglect.

PMID- 7723801
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 16-1995. A 35-year-old man with dilated cardiomyopathy, repeated
      ventricular tachycardia, and pulmonary lesions.

PMID- 7723799
TI  - Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as
      compared with streptokinase for acute myocardial infarction.
AB  - BACKGROUND: Patients with acute myocardial infarction who were treated with
      accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2
      hours rather than the conventional 3 hours, and with two thirds of the dose given
      in the first 30 minutes) had a 30-day mortality that was 15 percent lower than
      that of patients treated with streptokinase in the Global Utilization of
      Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries
      (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day
      mortality. We sought to assess whether the use of t-PA, as compared with
      streptokinase, is cost effective. METHODS: Our primary, or base-case, analysis of
      cost effectiveness used data from the GUSTO study and life expectancy projected
      on the basis of the records of survivors of myocardial infarction in the Duke
      Cardiovascular Disease Database. In the primary analysis, we assumed that there
      were no additional treatment costs due to the use of t-PA after the first year
      and that the comparative survival benefit of t-PA was still evident one year
      after enrollment. RESULTS: One year after enrollment, patients who received t-PA
      had both higher costs ($2,845) and a higher survival rate (an increase of 1.1
      percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On
      the basis of the projected life expectancy of each treatment group, the
      incremental cost-effectiveness ratio--with both future costs and benefits
      discounted at 5 percent per year--was $32,678 per year of life saved. The use of
      t-PA was least cost effective in younger patients and most cost effective in
      older patients. At all ages, the use of t-PA in patients with anterior
      infarctions yielded more favorable cost-effectiveness values. In our secondary
      analyses, the cost-effectiveness values were most sensitive to a lowering of the
      projected long-term survival benefits of t-PA and to moderate or greater
      increases in the projected medical costs for patients in the t-PA group after the
      first year. In contrast, our results were not sensitive to even very unfavorable
      assumptions about the additional costs associated with the higher rate of
      disabling stroke that was noted in patients treated with t-PA in the GUSTO study.
      CONCLUSIONS: The cost effectiveness of treatment with accelerated t-PA rather
      than streptokinase compares favorably with that of other therapies whose added
      medical benefit for dollars spent is judged by society to be worthwhile.

PMID- 7723802
TI  - The promiscuous receptor. Prostate cancer comes of age.

PMID- 7723803
TI  - Something new out of Africa.

PMID- 7723804
TI  - Cost effectiveness of tissue plasminogen activator.

PMID- 7723805
TI  - Using newly deceased patients in teaching procedures.

PMID- 7723806
TI  - Using newly deceased patients in teaching procedures.

PMID- 7723807
TI  - Using newly deceased patients in teaching procedures.

PMID- 7723808
TI  - Using newly deceased patients in teaching procedures.

PMID- 7723809
TI  - Deep-vein thrombosis.

PMID- 7723810
TI  - Deep-vein thrombosis.

PMID- 7723811
TI  - Deep-vein thrombosis.

PMID- 7723812
TI  - Thromboembolism after major trauma.

PMID- 7723813
TI  - Thromboembolism after major trauma.

PMID- 7723814
TI  - AMPAC campaign contributions to congress--a correction.

PMID- 7723815
TI  - Nonmelanoma skin cancer associated with use of a tanning bed.

PMID- 7723816
TI  - Patents for what genes?

PMID- 7723817
TI  - HUGO and HGS clash over 'utility' of gene sequences in US patent law.

PMID- 7723818
TI  - Protein institute gets a reprieve--and a new role.

PMID- 7723819
TI  - India seeks source of plague 'peculiarities'.

PMID- 7723820
TI  - Glaxo researchers move to new home.

PMID- 7723821
TI  - Hong Kong inquiry dispute.

PMID- 7723822
TI  - Neuropsychology. Acting without 'seeing'.

PMID- 7723823
TI  - In vitro evolution of a self-alkylating ribozyme.
AB  - RNA enzymes are postulated to have catalysed all chemical reactions in the
      earliest living cells. This idea is now investigated in a search for alkyl
      transferases from a pool of random sequence RNAs. Selection for self
      biotinylation yields a transfer RNA-like ribozyme that efficiently catalyses
      carbon-nitrogen bond formation. Ribozymes can thus promote reactions other than
      those involving the RNA sugar-phosphate backbone, suggesting that RNA may be
      capable of a broad range of catalytic activities.

PMID- 7723824
TI  - A brain-damaged patient with an unusual perceptuomotor deficit.
AB  - When interacting with objects, the pattern of movements is influenced by such
      object characteristics as size and position. Little is known about the effect of
      higher level categorical encoding of objects upon movements. Here we present
      evidence for an approval-for-action process which takes into account such
      encoding. For the brain-damaged subject L.P., the ability to complete actions
      involving two objects in central vision is influenced by the semantic or
      functional relationship between the objects. Even though she perceives only one
      object, she can integrate two related objects into a coordinated action. If the
      objects are not related she is unable to integrate them into a single motor act.
      We propose that selection-for-action systems include processes which gate
      conceptually the behavioural disposition to action.

PMID- 7723825
TI  - Independent neural mechanisms for bright and dark information in binocular
      stereopsis.
AB  - Early visual processing is organized into a number of independent channels. In
      the retina, increments and decrements of brightness are processed independently
      by different groups of neurons. For psychophysical measurements of human vision,
      independence can be tested statistically. Using this criterion in a depth
      judgement task, we show here that, for binocular stereo vision, increments and
      decrements are treated independently, at least as far as the level at which
      information from the left and right eyes is first combined. At later stages of
      stereo processing, the information from the two channels is no longer
      independent. Because the signals for stereo vision are first combined at the
      visual cortex, these results suggest that the neural 'on' and 'off' channels
      remain independent right up to early cortical stages. Theoretical studies of
      stereo vision have proposed that visual features in the views of the two eyes are
      matched on the basis of 'similarity'. Our results show that stereo matching
      treats features as statistically independent (and therefore dissimilar) if they
      appear perceptually bright and dark relative to the background. If features
      differ perceptually but only in the degree of brightness or darkness, human
      stereo vision treats them as similar.

PMID- 7723826
TI  - Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL.
AB  - The proto-oncogene bcl-2, isolated from the t(14;18) chromosomal breakpoint in
      follicular B-lymphoma, and a bcl-2-related gene bcl-x (ref. 4) prevent apoptotic
      cell death induced by various treatments. Although a mechanism has been proposed
      that involves Bcl-2 activity on reactive oxygen species (ROS), expression of Bcl
      2 or Bcl-xL prevents cell death induced by withdrawal of oxygen (hypoxia), which
      drastically decreases the net formation of oxygen free radicals and does not
      increase oxidized lipid, protein or DNA. Furthermore, neither ROS scavenger nor
      inhibitor of ROS scavenger affects cell death, regardless of the expression of
      Bcl-2 or Bcl-xL. Thus our data suggest that Bcl-2 and Bcl-xL exert an anti-cell
      death function by a mechanism other than regulation of ROS activity.

PMID- 7723827
TI  - A kinase from fission yeast responsible for blocking mitosis in S phase.
AB  - In virtually all eukaryotes, mitosis starts after the completion of DNA
      synthesis. This orderly process is ensured by the checkpoint mechanism that
      blocks the onset of mitosis while DNA is being synthesized or is damaged. In the
      fission yeast Schizosaccharomyces pombe, this mechanism involves some rad+ and
      hus+ genes. However, it is not known how the checkpoint system monitors these
      events. Recently a multicopy suppressor of a temperature-sensitive DNA polymerase
      alpha mutant was isolated. This gene, named cds1+ (checking DNA synthesis),
      encodes a typical protein kinase. Here we report that this protein kinase is a
      key component of the DNA replication-monitoring S/G2 checkpoint system. Our data
      suggest that its primary role is to monitor DNA synthesis by interacting with DNA
      polymerase alpha and send a signal to block the onset of mitosis while DNA
      synthesis is in progress.

PMID- 7723828
TI  - Connecting a promoter-bound protein to TBP bypasses the need for a
      transcriptional activation domain.
AB  - Biochemical analyses have suggested potential targets for transcriptional
      activation domains, which include several components of the RNA polymerase II
      machinery, as well as the chromatin template. Here we examine the mechanism of
      transcriptional activation in yeast cells by connecting a heterologous DNA
      binding domain (LexA) to the TATA-binding protein (TBP). LexA-TBP efficiently
      activates transcription from a promoter containing a LexA operator upstream of a
      TATA element. Activation is promoter-specific and is sensitive to mutations on
      the DNA-binding surface of TBP; hence it is not due to a fortuitous activation
      domain on TBP. Thus a promoter-bound protein lacking an activation domain can
      stimulate transcription if it is directly connected to TBP. This suggests that
      recruitment of TBP to the promoter can be a rate-limiting step for transcription
      in vivo, and that interactions between activation domains and factors that
      function after TBP recruitment can be bypassed for activation.

PMID- 7723829
TI  - Stimulation of RNA polymerase II transcription initiation by recruitment of TBP
      in vivo.
AB  - Eukaryotic transcriptional activators may stimulate RNA polymerase II activity by
      promoting assembly of preinitiation complexes on promoters through their
      interactions with one or more components of the basal machinery. On the basis of
      its central role in initiating transcription-complex formation upon binding to
      the TATA box, the general transcription factor TFIID, which includes the TATA
      binding protein (TBP) and several TBP-associated factors, has been implicated as
      a target for activators. Consistent with this idea, an increasing number of
      activators have been reported to bind directly to TBP. To assess the functional
      importance of these in vitro interactions for transcriptional regulation in vivo,
      we made use of a novel strategy in yeast to show that a physical interaction with
      TBP is sufficient for a sequence-specific DNA-binding protein to increase
      initiation of transcription by RNA polymerase II. These results imply that
      binding of TFIID to promoter elements is a limiting step in transcription complex
      assembly in vivo.

PMID- 7723830
TI  - The case for a great many journals.

PMID- 7723831
TI  - Solar system formation. Timing is everything.

PMID- 7723832
TI  - Genomic imprinting. Action at a distance.

PMID- 7723833
TI  - Locomotion. Freeloading women.

PMID- 7723834
TI  - Harold M. Weintraub (1945-95).

PMID- 7723835
TI  - Good manners win out.
AB  - Disputes about priority have no place in the seemly publication of research data.

PMID- 7723836
TI  - Allometry. Big flies have bigger cells.

PMID- 7723837
TI  - Cancer risk and electromagnetic fields.

PMID- 7723838
TI  - Cancer risk and electromagnetic fields.

PMID- 7723839
TI  - Anomaly admitted in 'first' AIDS case.

PMID- 7723840
TI  - MRC agrees terms of access to gene sequence databank.

PMID- 7723841
TI  - Energy-saving gait mechanics with head-supported loads.
AB  - In many areas of the world that lack a transportation infrastructure, people
      routinely carry extraordinary loads supported by their heads, for example the
      Sherpa of the Himalayas and the women of East Africa. It has previously been
      shown that African women from the Kikuyu and Luo tribes can carry loads
      substantially more cheaply than army recruits; however, the mechanism for their
      economy has remained unknown. Here we investigate, using a force platform, the
      mechanics of carrying head-supported loads by Kikuyu and Luo women. The weight
      specific mechanical work, required to maintain the motion of the common centre of
      mass of the body and load, decreases with load in the African women, whereas it
      increases in control subjects. The decrease in work by the African women is a
      result of a greater conservation of mechanical energy resulting from an improved
      pendulum-like transfer of energy during each step, back and forth between
      gravitational potential energy and kinetic energy of the centre of mass.

PMID- 7723842
TI  - Use of implicit motor imagery for visual shape discrimination as revealed by PET.
AB  - Positron emission tomography (PET) can be used to map brain regions that are
      active when a visual object (for example, a hand) is discriminated from its
      mirror form. Chronometric studies suggest that viewers 'solve' this visual shape
      task by mentally modelling it as a reaching task, implicitly moving their left
      hand into the orientation of any left-hand stimulus (and conversely for a right
      hand stimulus). Here we describe an experiment in which visual and somatic
      processing are dissociated by presenting right hands to the left visual field and
      vice versa. Frontal (motor), parietal (somatosensory) and cerebellar
      (sensorimotor) regions similar to those activated by actual and imagined movement
      are strongly activated, whereas primary somatosensory and motor cortices are not.
      We conclude that mental imagery is realized at intermediate-to-high order,
      modality-specific cortical systems, but does not require primary cortex and is
      not constrained to the perceptual systems of the presented stimuli.

PMID- 7723843
TI  - Homeotic genes and the regulation and evolution of insect wing number.
AB  - The evolution of wings catalysed the radiation of insects which make up some 75
      per cent of known animals. Fossil evidence suggests that wings evolved from a
      segment of the leg and that early pterygotes bore wings on all thoracic and
      abdominal segments. The pterygote body plan subsequently diverged producing
      orders bearing three, two or just one pair of thoracic wings. We have
      investigated the role of homeotic genes in pterygote evolution by examining their
      function in Drosophila wing development and their expression in a primitive
      apterygote. Wing formation is not promoted by any homeotic gene, but is repressed
      in different segments by different homeotic genes. We suggest here that wings
      first arose without any homeotic gene involvement in an ancestor with a homeotic
      'groundplan' similar to modern winged insects and that wing formation
      subsequently fell under the negative control of individual homeotic genes at
      different stages of pterygote evolution.

PMID- 7723844
TI  - Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in
      immunodeficient mice blocked by a human pregnancy hormone.
AB  - Kaposi's sarcoma (KS) occurs more often in men than in women and HIV-1-associated
      KS has a high occurrence in homosexual men (over 30%). Most cultures of KS
      tumours yield cells with properties of hyperplastic (not malignant) endothelial
      cells under the control of several cytokines. The role of HIV-1 may be in
      promoting high levels of some cytokines and providing stimulation to angiogenesis
      by the HIV-1 Tat protein, which synergizes with basic fibroblast growth factor in
      promoting these effects. Here we describe an immortalized AIDS-KS cell line (KS Y
      1) and show that these cells produce malignant metastatic tumours in nude mice
      and are killed in vitro and in vivo (apparently by apoptosis) by a pregnancy
      hormone, the beta-chain of human chorionic gonadotropin. Similarly, chorionic
      gonadotropin kills KS SLK, cells from another neoplastic cell line (established
      from a non-HIV-associated KS), as well as the hyperplastic KS cells from clinical
      specimens grown in short-term culture, but does not kill normal endothelial
      cells. These results provide evidence that KS can evolve into a malignancy and
      have implications for the hormonal treatment of this tumour.

PMID- 7723845
TI  - Swedish council is dismissed amid claims of malpractice.

PMID- 7723846
TI  - A calcium-channel homologue required for adaptation to dopamine and serotonin in
      Caenorhabditis elegans.
AB  - Processing and storage of information by the nervous system requires the ability
      to modulate the response of excitable cells to neurotransmitter. A simple process
      of this type, known as adaptation or desensitization, occurs when prolonged
      stimulation triggers processes that attenuate the response to neurotransmitter.
      Here we report that the Caenorhabditis elegans gene unc-2 is required for
      adaptation to two neurotransmitters, dopamine and serotonin. A loss-of-function
      mutation in unc-2 resulted in failure to adapt either to paralysis by dopamine or
      to stimulation of egg laying by serotonin. In addition, unc-2 mutants displayed
      behaviours similar to those induced by serotonin treatment. We found that unc-2
      encodes a homologue of a voltage-sensitive calcium-channel alpha-1 subunit.
      Expression of unc-2 occurs in two types of neurons implicated in the control of
      egg laying, a behaviour regulated by serotonin. Unc-2 appears to be required in
      modulatory neurons to downregulate the response of the egg-laying muscles to
      serotonin. We propose that adaptation to serotonin occurs through activation of
      an Unc-2-dependent calcium influx, which modulates the postsynaptic response to
      serotonin, perhaps by inhibiting the release of a potentiating neuropeptide.

PMID- 7723847
TI  - Chiron expands gene therapy efforts.

PMID- 7723848
TI  - Questionnaire row returns to the courts.

PMID- 7723849
TI  - Allosteric transition intermediates modelled by crosslinked haemoglobins.
AB  - The structural end-points of haemoglobin's transition from its low-oxygen
      affinity (T) to high-oxygen-affinity (R) state, have been well established by X
      ray crystallography, but short-lived intermediates have proved less amenable to X
      ray studies. Here we use chemical crosslinking to fix these intermediates for
      structural characterization. We describe the X-ray structures of three
      haemoglobins, alpha 2 beta 1S82 beta, alpha 2 beta 1Tm82 beta and alpha 2 beta
      1,82Tm82 beta, which were crosslinked between the amino groups of residues beta
      Val1 and beta Lys82 by 3,3'-stilbenedicarboxylic acid (S) or trimesic acid (Tm)
      while in the deoxy state, and saturated with carbon monoxide before
      crystallization. alpha 2 beta 1S82 beta, which has almost normal oxygen affinity,
      is completely in the R-state conformation; however, alpha 2 beta 1Tm82 beta and
      alpha 2 beta 1,82Tm82 beta, both of which have low oxygen affinity, have been
      prevented from completing their transition into the R state and display many
      features of a transitional intermediate. These haemoglobins therefore represent a
      snapshot of the nascent R state.

PMID- 7723851
TI  - [Cadmium concentrations in tobacco in cigarettes smoked in Germany in 1978, 1985
      and 1994: a comparison].

PMID- 7723852
TI  - Specific enhancement of olfactory receptor sensitivity associated with foetal
      learning of food odors in the rabbit.

PMID- 7723850
TI  - Molecular mechanisms of tissue determination and pattern formation in amphibian
      embryos.
AB  - Factors of the TGF-beta superfamily (activin, vegetalizing factor) and the FGF
      family determine endoderm and mesoderm. The dorsoventral polarity of the mesoderm
      depends on additional factors (BMP-4, Wnt-8, noggin). Activin can directly
      activate gene transcription by signal transduction. Mesoderm is determined by
      factors prelocalized in the marginal zone. Its differentiation depends also on
      the animal ectoderm. Neural inducing factors have been partially purified. A
      masked neuralizing factor in the ectoderm is activated by induction of the
      ectoderm to the nervous system. Phorbolester can evoke neuralization signaling.

PMID- 7723853
TI  - NKF finalizes report on controversies in dialysis.

PMID- 7723854
TI  - An alternative view of the consequences of an extension of the Medicare secondary
      payer period.

PMID- 7723856
TI  - Tools are available to conquer vascular access problems--let's use them!

PMID- 7723855
TI  - The costs of hospitalizations due to hemodialysis access management.

PMID- 7723857
TI  - A CQI approach to improved vascular access outcomes.

PMID- 7723858
TI  - RAND Report: Medicare spent $383 million on placing vascular access grafts in
      1990.

PMID- 7723859
TI  - What to do when the water stops.

PMID- 7723860
TI  - Setting up a water treatment system in an acute care setting.

PMID- 7723861
TI  - Evaluation: a progress report on measuring rehabilitation outcome. Part II.

PMID- 7723862
TI  - Dear NKF: "Where's the beef?".

PMID- 7723863
TI  - Medical investigator re-opens case involving dialysis patient's death in New
      Mexico.

PMID- 7723864
TI  - [Anal blood loss in pregnancy, a symptom which should be taken seriously].

PMID- 7723865
TI  - [Quality promotion and re-registration of medical specialists].

PMID- 7723866
TI  - [Diagnosis and treatment of lymphedema].

PMID- 7723867
TI  - [Initial experiences with home care for peritoneal dialysis rendered by district
      nurses].
AB  - OBJECTIVE: To investigate the feasibility of home care for continuous ambulatory
      peritoneal dialysis (CAPD) by district nurses. DESIGN: Descriptive study.
      SETTING: Free University Hospital in Amsterdam. PATIENTS: Patients with end-stage
      renal disease who were eligible for CAPD but were not able to carry out the CAPD
      treatment themselves were given assistance by district nurses. During the study
      period from December 1991 to December 1992 the patients' clinical scores were
      recorded every 3 months, and questionnaires were sent to both the district and
      the hospital nurses. RESULTS: During the study period 58 months of CAPD home care
      were given to ten patients (average age 74 years) by 159 community nurses. These
      had received a preliminary training by the staff of the dialysis department and
      they were supported by consultation. Three patients died during the study period.
      Five patients continued the CAPD home care treatment after December 1992.
      CONCLUSION: CAPD home care by district nurses is feasible on the following
      conditions: extra financing, preliminary training and support for the district
      nurses from the hospital staff by consultation.

PMID- 7723868
TI  - [The Dutch version of the McGill pain questionnaire: a reliable pain
      questionnaire].
AB  - OBJECTIVE: To assess whether the McGill pain questionnaire, translated into Dutch
      (MPQ-DLV), is a reliable instrument to measure pain. DESIGN: Questionnaire study.
      SETTING: Faculty of Social Sciences, University of Leiden, the Netherlands.
      METHOD: The MPQ-DLV was administered three times to 92 patients who had
      physiotherapy: in group I (n = 62) twice before and four hours after
      physiotherapy treatment, in group II (n = 30) before, directly after and four
      hours after treatment. The questionnaire consisted of questions to determine (a)
      the quality and intensity, (b) the localisation and evolution of the pain, (c)
      the effects of the pain on quality of life and further (d) visual analog pain
      intensity scales. Subsets of questions were combined into nine indices. For all
      indices on all three occasions Cronbach's alpha coefficients were determined.
      Moreover, test-retest correlation coefficients were determined between the scores
      of the first and second, the first and third, and the second and third occasions.
      RESULTS: The test-retest correlations of the nine indices and the visual analog
      pain intensity scales ranged from 0.62 to 0.93 (median: 0.84). Cronbach's alpha
      coefficients for the indices varied between 0.61 and 0.85 (median: 0.72).
      CONCLUSION: The MPQ-DLV is a reliable instrument for measuring pain.

PMID- 7723869
TI  - [Life-threatening angioedema as a side effect of angiotensin-converting-enzyme
      (ACE) inhibitors].
AB  - During the past years, angioedema occurring in association with angiotensin
      converting enzyme (ACE) inhibitors is seen more and more often. This is due to
      the increasing use of these drugs for hypertension and congestive heart failure.
      If the diagnosis is missed and prescription of the ACE inhibitor is prolonged,
      recurrent and more severe episodes of angioedema may occur. In case of
      involvement of the upper airway and respiratory distress, the condition may be
      life-threatening. We demonstrate three such patients, men of 84, 73 and 63 years
      old. First of all, the airway should be secured. Administration of epinephrine
      may be indicated. Further use of ACE inhibitors is contraindicated.

PMID- 7723870
TI  - [Prevention and curative health care for children: an interaction].

PMID- 7723871
TI  - [The development of peer review among medical specialists in Dutch hospitals:
      self-regulation under pressure].

PMID- 7723872
TI  - [Practice comparison offers clues for improvement of practice management:
      inspection obstetrics and gynecology as an example].

PMID- 7723873
TI  - [Fewer headaches following lumbar puncture when using an atraumatic needle;
      double-blind randomized study].

PMID- 7723874
TI  - [Fewer headaches following lumbar puncture when using an atraumatic needle;
      double-blind randomized study].

PMID- 7723875
TI  - [Acute rheumatoid arthritis or post-streptococcal reactive arthritis; an
      unexpected reactivation in The Netherlands].

PMID- 7723876
TI  - [Budd-Chiari syndrome: current viewpoints and developments].

PMID- 7723877
TI  - [Surgery? Nearly always!].

PMID- 7723878
TI  - [Treatment of anemia in premature infants using recombinant human
      erythropoietin].

PMID- 7723879
TI  - [Secondary resuscitation treatment: guidelines of the European Resuscitation
      Council 1992. Work Group Advanced Life Support of the European Resuscitation
      Council].

PMID- 7723880
TI  - [Congenital ptosis of the upper eyelid: indication for early ophthalmological
      examination].
AB  - OBJECTIVE: Description of the results of clinical investigation and surgical
      correction in patients with congenital upper eyelid ptosis. DESIGN: Descriptive.
      SETTING: The Eye Hospital, Rotterdam. METHOD: Evaluation of clinical findings and
      results of operative treatment in 114 consecutive patients with congenital
      ptosis. RESULTS: Amblyopia was present in 20% of the 114 patients, and was caused
      by stimulus deprivation due to the ptotic eyelid (22%), strabismus (48%), and
      refraction disorder (30%). Treatment of amblyopia did not induce visual
      improvement in 7% of the patients (8/114). These patients were all older than 7
      years, meaning they were probably too old for treatment. Of the 114 patients, 14%
      showed strabismus without amblyopia, 8% showed abnormalities of eye movement
      without squint, and 6% showed torticollis due to the ptosis. At time of referral
      28% were younger than 6 years and 35% had already been treated surgically for the
      ptosis elsewhere. Operative correction of ptosis induced symmetry within 1 mm in
      62%, and symmetry within 2 mm in 22%. Reoperation was performed in 16%. Previous
      operation elsewhere had no influence on the results. CONCLUSIONS: Patients with
      congenital ptosis frequently show amblyopia, strabismus, and abnormalities of eye
      movement. In the patients referred to us, amblyopia had not always been diagnosed
      and treated in time. Ophthalmological examination in the first year of life is
      indicated in these patients. If the ptotic eyelid induces deprivation amblyopia
      or torticollis, direct ptosis correction is indicated. It is advised for
      psychological reasons to correct elective cases at the age of 4 or 5 years. For
      this reason, also, patients should be referred sooner.

PMID- 7723881
TI  - [Feasibility of transferring medical-technological aid to the home situation for
      patients with cancer or a serious infection].
AB  - OBJECTIVE: To describe the feasibility of home care technology for patients with
      cancer or serious infectious diseases. SETTING: Utrecht. METHODS: One hundred and
      thirty one patients with cancer or serious infections were treated at home with
      parenteral administration of fluid, cytostatics, analgetics, blood products or
      antimicrobial agents. A 24-hour service team was available to support patients,
      their families and professional care-givers. The team is responsible for the
      education, the development of protocols and logistic co-ordination such as the
      supply of materials in the home setting. RESULTS: During a period of about 10,000
      days (median 41 days per patient) the supportive team was consulted 127 times. In
      five cases hospitalization was necessary, no patient died of a complication.
      Instruction was given to 74 general practitioners; 32 of them were able to handle
      medical technology on their own. Time consumption due to incidents was 0.8 minute
      per day and 57 minutes per patient. CONCLUSION: Under certain conditions, notably
      a supporting team, home care technology is feasible.

PMID- 7723882
TI  - [Age, desire for children and probability of pregnancy in The Netherlands].
AB  - OBJECTIVE: To investigate the relation between the age of women and their
      probability of conceiving, and to analyse the factors that influence the age at
      which couples desire to have their first child. METHOD: A national survey among
      women between the ages of 25 and 49. A random sample of 8050 households were
      approached. In these households 3295 women between the ages of 25 and 49 answered
      a short questionnaire about planning of the first pregnancy and fertility. Also
      sociodemographic data were gathered. RESULTS: There was little variation in
      probability of conceiving between the ages of 20 and 28; around 65% to 70% after
      6 months, just below 90% after 12 months and about 93% after 2 years. The
      pregnancy rate after 6 months started to decrease after the age of 33, while
      pregnancy rate after 1 and 2 years decreased gradually from the age of 28 to 75%
      and about 80% respectively at the age of 35. The year of birth of the woman (the
      factor 'time') was the most important factor influencing the age at which couples
      desire their first child. In addition demographic factors particularly a high
      level of education, and furthermore a high professional level and a high level of
      family income were associated with the desire to have the first child at a
      relatively late age.

PMID- 7723883
TI  - [Wilson's disease; diagnosis with the aid of magnetic resonance tomography].
AB  - In a 21-year-old woman with a smaller and sloppy handwriting, drooling especially
      when stooping, sporadic choking, clumsiness, and frequent stumbling, Wilson's
      disease was diagnosed. The medical history disclosed a short period of haemolytic
      anaemia with transient hepatic failure, and irregular menstruation periods with
      infertility. On examination there were no signs of liver or spleen enlargement.
      She was slow, had an expressionless face and mild dysarthria, and slight
      impairment of the coordination of the limbs. Magnetic resonance imaging of the
      brain showed bilateral hyperintensive lesions of the basal ganglia on T2W images.
      Zinc therapy induced a good biochemical response and there was also some clinical
      improvement. Linkage analysis within the family identified one other asymptomatic
      homozygotically affected sister. A diagnostic delay occurs frequently due to
      relative unfamiliarity with this rare disease and due to its variable clinical
      expression.

PMID- 7723884
TI  - [Underestimation of intestinal protozoa as a cause of diarrhea in family
      practice].

PMID- 7723885
TI  - [Underestimation of intestinal protozoa as a cause of diarrhea in family
      practice].

PMID- 7723886
TI  - [Delirium in the nursing home].

PMID- 7723887
TI  - [Delirium in the nursing home].

PMID- 7723888
TI  - [Delirium in the nursing home].

PMID- 7723889
TI  - [Subfertility in South Limburg: calculation of incidence and appeal for
      specialist care].

PMID- 7723890
TI  - [HIV infection in the Rijnmond region, 1985-1993: more transmission via
      heterosexual contact and drug abuse and more female patients].

PMID- 7723891
TI  - [No positive effect of preoperative exercise therapy and teaching in patients to
      be subjected to hip arthroplasty].

PMID- 7723892
TI  - Lipoprotein(a) levels and fibrinolytic activity in patients with nephrotic
      syndrome.
AB  - Recently there has been a renewed interest in the possibility that lipoprotein(a)
      -Lp(a)--may be important in the pathogenesis of thrombosis-related disease. In
      nephrotic syndrome, hyperlipidemia is a common finding, and thrombosis is a major
      complication. With this regard, if Lp(a) levels increase concomitantly with low
      density lipoprotein and/or very-low-density lipoprotein levels in nephrotic
      syndrome, this may be considered a thrombogenic factor. To probe this possibility
      and to corroborate the relationship between Lp(a) and fibrinolytic profiles, we
      measured the Lp(a) levels in patients with nephrotic syndrome (n = 43), in
      patients with chronic glomerulonephritis with less proteinuria than in nephrotic
      syndrome (n = 28), and in healthy controls (n = 50) and observed the relation
      between Lp(a) levels and tissue-type plasminogen activator (t-PA) activity,
      euglobulin fibrinolytic activity, and t-PA antigen. The Lp(a) levels were
      significantly higher in the patients with nephrotic syndrome as compared with
      both patients with chronic glomerulonephritis and healthy controls (p < 0.001).
      There was a direct correlation with serum cholesterol level (r = 0.780; p =
      0.0001), triglyceride level (r = 0.445; p = 0.0001), and urine protein level (r =
      0.675; p = 0.0001) and a reverse correlation with serum albumin levels (r =
      0.566; p = 0.0001). The Lp(a) levels showed a reverse correlation with t-pA
      activity (r = 0.627; p = 0.0001), total fibrinolytic activity in euglobulin
      fraction (r = 0.458; p = 0.0001), and t-PA activity divided by the t-PA antigen
      (r = 0.567; p = 0.0001), but no correlation with t-PA antigen.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7723893
TI  - Clinical course of focal segmental glomerulosclerosis associated with
      hepatosplenic schistosomiasis mansoni.
AB  - To analyze the clinical course and response to therapy 15 patients (9 male and 6
      female) with the hepatosplenic form of schistosomiasis mansoni and focal
      segmental glomerulosclerosis (FSGS) were prospectively studied (mean follow-up =
      115.8 +/- 93.2 months). Nephrotic syndrome was the most frequent clinical
      presentation, followed by abnormalities of urinalysis. The clinical course was
      progressive: at final evaluation 9 patients (60%) had developed renal failure.
      Hypertension or/and renal insufficiency at initial evaluation and persistence of
      the nephrotic syndrome were associated with progression toward advanced renal
      failure. Response to immunosuppressive therapy was recorded in 30% of the
      patients; all responsive patients still had normal renal function at final
      evaluation. The treatment of the Schistosoma mansoni infection did not influence
      the clinical course of the renal disease. It is concluded that FSGS in patients
      with hepatosplenic schistosomiasis mansoni is a disease progressing to advanced
      stage independently of the presence of the parasite.

PMID- 7723894
TI  - Decreased platelet counts and decreased platelet serotonin in poststreptococcal
      nephritis.
AB  - Mean platelet survival time in patients with acute poststreptococcal
      glomerulonephritis (APSGN) is reduced to 50-60% of the control values, and
      glomerular deposits of platelet factor 4 are found in these patients. In order to
      investigate further systemic platelet changes of pathogenic, clinical or
      prognostic significance, we measured the platelet serotonin (5-HT) content and
      the blood platelet counts during the 1st week of the disease in 27 patients with
      APSGN. Platelet 5-HT was significantly reduced in patients with APSGN as compared
      with patients with impetigo without glomerular involvement (785 +/- 54 vs. 1,329
      +/- 94 ng 5-HT/10(9) platelets; p < 0.001). Similarly, the mean blood platelet
      count was reduced to 247 +/- 16 x 10(3) as compared with 303 +/- 14 x 10(3) in
      the controls (p < 0.05). Thirteen (48%) of these patients had individual values
      of platelet 5-HT lower than the 95% confidence interval calculated in the control
      group. No significant correlation was observed between the concentration of 5-HT
      and either the severity of the disease judged by the amount of urinary protein
      excretion and the serum creatinine value or the presence of circulating immune
      complexes. Significant correction of the platelet 5-HT content (to 1,180 +/- 111
      ng/10(9) platelets; p < 0.01) and of the platelet counts (to 309 +/- 21 x 10(3);
      p < 0.01) were observed in the longitudinal study at least 2 weeks later.
      Platelet activation, with secretion of granular content and increased
      consumption, may explain these findings. Additionally, the reduced mean age of
      the circulating platelets could contribute to their decreased 5-HT
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723895
TI  - Glomerular filtration rate and urinary albumin excretion rate in systemic lupus
      erythematosus.
AB  - Our objective was to more precisely determine glomerular function in patients
      with systemic lupus erythematosus (SLE), without abnormalities in renal function,
      as determined by standard clinical laboratory tests. Our long-term goal is to
      identify patients during clinical quiescence who may be at high risk of
      developing progression to renal failure from lupus nephritis. We studied three
      groups of subjects: 8 patients with SLE and a history of nephritis, now in
      remission; 25 patients with SLE, without clinical evidence of nephritis, now or
      in the past; and 5 healthy women (normal controls). At the time of study,
      urinalysis, serum creatinine and 24-hour urine total protein excretion were
      within the normal range in each subject. We measured glomerular filtration rate
      (GFR) by 125I-iothalamate clearance, and albumin excretion rate (AER) by enzyme
      linked immunosorbent assay (ELISA) in timed urine specimens. In addition, we
      compared 4-hour AER with 24-hour AER and spot urine albumin/creatinine ratio
      (A/C). Among patients with a history of nephritis now in remission, mean GFR was
      slightly but not significantly lower and mean AER was elevated (p < 0.03). Among
      patients with SLE without a history of nephritis, mean GFR was normal, but the
      variance in GFR was greater than normal (p < 0.005). Seven patients without
      nephritis (28%) had either hyperfiltration or hypofiltration. Mean AER was
      normal, but 3 other patients (12%) had elevated AER. There was no correlation of
      GFR and AER among patients in either group. Correlations (r) of spot urine A/C
      and 24-hour AER with 4-hour AER were 0.93 (p < 0.001) and 0.88 (p < 0.001),
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723896
TI  - Effects of oral administration of zinc and diiodohydroxyquinolein on plasma zinc
      levels of uremic patients.
AB  - Patients with chronic renal failure often have low plasma zinc (Zn) levels. Some
      factors that may account for abnormal Zn metabolism in these patients are low
      dietary Zn intake, a specific Zn transport defect, or absence of intestinal Zn
      ligand. In this study Zn supplementation and a Zn-chelating drug,
      diiodohydroxyquinolein (DQ), were used to assess the effects of Zn intake and Zn
      transporters on Zn plasma levels in patients with chronic renal failure. To meet
      this objective, 20 uremic patients were randomly assigned to one of the following
      groups of treatment: group 1 received placebo; group 2 Zn sulfate (100 mg/day
      p.o.), group 3 DQ (80 mg/day p.o.), and group 4 received Zn sulfate plus DQ at
      the same dosages as in groups 2 and 3. The Zn plasma levels were measured in
      venous samples, before and after 1 and 2 weeks of treatment, by atomic absorption
      spectrophotometry. The Zn plasma levels increased in group 2 patients from 8 +/-
      0.2 to 10 +/- 0.4 and 11 +/- 0.9 mumol/l by the end of the 1st and 2nd weeks of
      treatment, respectively. In group 4 patients, the Zn plasma levels increased even
      more: from 9 +/- 0.1 to 14 +/- 1.6 and 13 +/- 2.1 mumol/l respectively. The
      plasma Zn concentration of group 1 and 3 patients remained at basal levels. These
      results show that DQ, when given along with Zn sulfate supplements, causes a
      greater increase in plasma Zn levels than that caused by either drug given alone.

PMID- 7723897
TI  - Possible role of mevalonate in the hypercholesterolemia seen in experimental
      chronic renal failure.
AB  - Hypercholesterolemia may contribute to the pathogenesis of atherosclerosis
      associated with chronic renal failure (CRF). The mechanism underlying CRF-induced
      hypercholesterolemia, however, is still unknown. Mevalonate is the direct product
      of the rate-limiting step in cholesterol synthesis which is catalyzed by 3
      hydroxy-3-methylglutaryl coenzyme A reductase. We studied the changes in
      mevalonate metabolism in a mouse model of CRF in which serum total cholesterol
      levels are directly correlated with the degree of severity of the disease as
      measured by serum urea levels. The results of these experiments indicated that in
      CRF mice, the urine mevalonate levels were significantly lower, while serum
      mevalonate and total cholesterol levels were significantly higher than in normal
      mice. We believe that by restricting the normal urinary excretion of mevalonate
      CRF results in more of this precursor being available for direct cholesterol
      synthesis. In addition, an increase in circulating mevalonate may upregulate the
      shunt pathway of mevalonate metabolism in the liver and peripheral tissues, thus
      providing increased levels of the substrates acetoacetate and acetyl coenzyme A
      for cholesterol synthesis.

PMID- 7723898
TI  - Agmatine and spermidine reduce collagen accumulation in kidneys of diabetic db/db
      mice.
AB  - In the present study, we tested the hypothesis whether agmatine and spermidine,
      metabolites of arginine metabolism, share the pharmacological activities of
      arginine reducing collagen accumulation in the diabetic kidney. Eleven db/db mice
      were administered agmatine and 12 db/db mice spermidine (50 mg/kg body weight).
      Ten db/db mice received no treatment as negative controls and 10 db/db mice were
      treated with aminoguanidine (50 mg/kg body weight) as positive controls. Mean
      kidney OH-proline content reflecting kidney collagen content and mean CML
      concentration were significantly higher but acid solubility of collagen
      significantly lower in the untreated group than in the treated groups. Agmatine,
      although missing the alpha-amino group and the carboxyl group, and spermidine,
      although missing the guanidino group, thus still revealed the arginine activity.
      We hypothesize that the strongly nucleophilic structure of polyamines common to
      all active compounds is able to block reactive carbonyls.

PMID- 7723900
TI  - Renal cell carcinoma presenting as nephrotic syndrome.
AB  - A 64-year-old woman presenting with a history of increasing oedema was found to
      have nephrotic syndrome with a 24-hour urinary protein excretion of 20.7 g and
      renal impairment with an initial serum creatinine level of 197 mumol/l (2.16
      mg/dl). A renal tumour was demonstrated by ultrasound scanning and subsequent
      nephrectomy revealed a renal carcinoma extending as far as the resected end of
      the renal vein. Histology of the kidney not involved by the tumour showed normal
      light microscopic appearances, with electron microscopy demonstrating foot
      process fusion, suggesting a diagnosis of minimal-change nephropathy. Nephrotic
      syndrome is a rare complication of renal cell carcinomas, and it is particularly
      uncommon for minimal change nephropathy to be associated with solid tumours.

PMID- 7723899
TI  - Estrogen attenuates progressive glomerular injury in hypercholesterolemic male
      Imai rats.
AB  - Hypercholesterolemic Imai rats spontaneously develop proteinuria and
      glomerulosclerosis, especially in males. A sex difference in glomerular injury
      has been recognized, but the role of sex hormones in glomerular injury remains
      unclear. Therefore, we investigated whether estrogen administration influences
      the progressive glomerular injury in male Imai rats. Estrogen produced a
      significant decrease in body weight. Systolic blood pressure in estrogen-treated
      rats was significantly lower than that in controls. Estrogen attenuated the
      progression of glomerular injury by significantly reducing proteinuria and
      glomerular sclerosis. The glomerulosclerosis index was significantly higher in
      controls than in estrogen-treated rats. Estrogen suppressed serum testosterone
      levels, whereas it increased GH levels. Results suggest that estrogen appears to
      play an inhibitory role on the development of glomerular injury, by itself or in
      association with sex-related factors regulated by estrogen and testosterone.

PMID- 7723901
TI  - Effects of dietary manipulation with fish oil on platelet receptors for von
      Willebrand factor and fibrinogen in patients with end-stage renal disease.

PMID- 7723902
TI  - Vasoactive intestinal contractor as a genesis of renal hypertension.

PMID- 7723903
TI  - Possible protective effect of chronic renal failure against sepsis and endotoxin
      induced organ failure and mortality in acute renal failure.

PMID- 7723904
TI  - Magnetic resonance imaging diagnosis of right atrial septic thrombus caused by
      subclavian catheter in a hemodialysis patient.

PMID- 7723905
TI  - A case of thrombotic thrombocytopenic purpura successfully treated with
      cyclophosphamide.

PMID- 7723906
TI  - Detection of myeloma casts by Evans blue in kidney biopsy specimens and urinary
      sediment.

PMID- 7723907
TI  - Mesangiocapillary glomerulonephritis associated with hereditary angioedema.

PMID- 7723908
TI  - Polymerase chain reaction for the diagnosis of viral hepatitis C in clinical
      medicine.

PMID- 7723909
TI  - Prevalence of hepatitis C virus RNA in hemodialysis patients: comparison of four
      antibody assays.

PMID- 7723910
TI  - Relapse of systemic lupus erythematosus after extracorporeal immunoadsorption.

PMID- 7723911
TI  - Dihydroergocristine-induced retroperitoneal fibrosis with an episode of
      reversible obstructive acute renal failure.

PMID- 7723912
TI  - Paraffin-processed material is unsuitable for diagnosis of thin-membrane disease.

PMID- 7723913
TI  - Gain in recombinant human erythropoietin dosage with continuous intravenous
      intradialytic administration for the treatment of anaemia in end-stage renal
      disease.

PMID- 7723914
TI  - Arteriovenous fistula and renal artery stenosis in a transplant kidney.

PMID- 7723915
TI  - Renal hydatid cyst detected in a child during the course of acute
      poststreptococcal glomerulonephritis.

PMID- 7723916
TI  - Serum lipoprotein(a) as an independent cardiovascular risk factor for patients
      undergoing chronic hemodialysis.

PMID- 7723917
TI  - Correction of amino acid metabolism during rhEPO therapy in hemodialysis patients
      results from a better oxygen availability.

PMID- 7723918
TI  - Blood amino acid levels and erythropoietin treatment in hemodialysis patients.

PMID- 7723919
TI  - Effects of dietary lipids and lovastatin during the course of nephropathies.

PMID- 7723920
TI  - Pulmonary hemorrhage in renal transplant recipients.

PMID- 7723921
TI  - [Does hemangioblastoma exist outside von Hippel-Lindau disease?].
AB  - Hemangioblastoma may arise in isolation ("sporadic" cases) or as a major
      manifestation of von Hippel-Lindau (VHL) disease, an autosomal dominant disorder
      with a prevalence of at least 1/36,000. In addition of central nervous system
      hemangioblastomas (cerebellum, spinal cord and retina), affected patients may
      develop renal cysts or carcinomas, pheochromocytomas and pancreatic cysts. A
      multidisciplinary group including neurosurgeons, geneticists, pathologists and
      clinicians from all involved specialities has been organized to develop a
      national registration of all hemangioblastoma and VHL patients. The findings of a
      preliminary 10-year study (1983-1993) conducted in France are presented. Two
      hundred thirteen cases of hemangioblastoma were reviewed for their location and
      genetic features. The majority (77%) of the tumors were located in the cerebellum
      whereas 23% were located inside the spinal canal. By thorough clinical
      examination of the patients and systematic genetic inquiry of their family
      background, it was found that 34.3% of the total (58.7% before age 30) were
      afflicted with VHL disease. Spinal hemangioblastomas were more often related to
      VHL disease than infra-tentorial locations (50% versus 36.6%). In addition, mean
      age at diagnosis in VHL disease was significantly younger than in sporadic cases
      (33.5 +/- 10 versus 43.6 +/- 15 years). Recent progress in VHL molecular genetics
      led to the identification of the mutated gene to the distal part of the short arm
      of chromosome 3 (3p25-3p26), paving the way to presymptomatic diagnosis and,
      hopefully, to elucidation of pathogenesis, which may offer a further glimpse into
      tumorigenesis in general. Because of the usually early adulthood onset, accurate
      presymptomatic diagnosis of affected members would be of great benefit to VHL
      families. However, the fact that very few mutations in the VHL gene are
      identified precludes molecular diagnosis of "sporadic" hemangioblastomas. In
      summary, this study reveals that VHL-related hemangioblastoma is a more common
      clinical problem that it was previously reported. Thus, all patients with an
      apparently isolated central nervous system hemangioblastoma should be
      investigated for evidence of VHL disease.

PMID- 7723922
TI  - [Magnetic resonance imaging of intraspinal hemangioblastoma].
AB  - Magnetic resonance (MR) findings in 16 patients operated on 21 spinal cord
      hemangioblastomas were reviewed. Three of these patients had von Hippel-Lindau
      syndrome. 13 patients had Gadolinium-DTPA enhanced MR and 2 had dynamic
      sequences. Using Gd-DTPA makes the diagnosis of hemangioblastomas considerably
      easier compared to conventional non contrast MR. Findings are specific: a tumor
      nodule with, as a general rule, an extensive cyst formation; the nodule shows
      intense, earliness, homogeneous contrast enhancement as the cyst wall does not.
      In less typical cases, dynamic sequences may be useful in order to distinguish
      hemangioblastoma from other spinal cord tumor nodules. Today, MRI is the
      diagnostic modality of choice and angiography should not be used. MRI is also an
      excellent way to check the central nervous system and the visceral manifestations
      in a case of von Hippel-Lindau disease and to follow up the patients.

PMID- 7723923
TI  - [Intraspinal hemangioblastoma. Apropos of a recent series of 20 cases].
AB  - This report deals with a series of 20 patients admitted for a spinal
      hemangioblastoma between 1970 and 1993, 18 of whom between 1978 and 1993. There
      are 8 men and 12 women and the onset of spinal symptoms is before the age of 50
      years for 76% of the patients. Nineteen patients have an intra-dural tumor
      (extramedullary 15.5%, intramedullary 75% with 62.5% close to the dorsal surface,
      37.5% partly out, none totally enclosed with spinal cord) and only one patient
      has an extra-dural tumor. Cysts are present in 70% of our cases. Two cases have
      been revealed by an hemorrhagic syndrome. Ten cases belong to a von Hippel-Lindau
      (vHL) disease. Nineteen patients were operated on, one patient died. Total
      resection of the tumor was performed in 17. Symptoms improved postoperatively in
      8 patients, were inchanged in 6, and worsened temporary in 4. MRI with gadolinium
      is the best procedure for both the diagnosis and the follow-up. After surgery,
      the prognosis is very good for sporadic cases with a single spinal lesion whereas
      it is very poor in case of vHl disease. For these patients (50% of our cases),
      half of them died because of the evolution of multifocal lesions even if they
      were operated on several times. Thus, each patient should have a precise check-up
      (SNC and visceral lesions). The gene causing vHL disease located on the short arm
      of the chromosome 3 has just been characterized. This will help to elaborate a
      presymptomatic diagnosis and a better screening of the patients with the hope of
      a specific treatment.

PMID- 7723924
TI  - [Epidemiology of narrow spinal canal].
AB  - During a period of 4.5 years, 199 patients have been operated on by laminectomy
      because of narrow lumbar canal. The incidence in Geneva is about 11.5
      case/100000/year and the ratio between male and female is 1.28. The disease is
      strongly related to aging, but men are affected earlier in their life than women.
      Heavy work, particularly for men, has a part to play in the genesis, like the
      body mass calculated by BMI (Body Mass Index). A comparison between the
      epidemiology of lumbar disc prolapse and lumbar stenosis shows the differences.

PMID- 7723925
TI  - Radicular compression by gas in a spinal extra dural cyst. Report on two cases.
AB  - The authors describe two cases of secondary sciatica due to radicular compression
      by a gas containing cyst in the extra dural space. The diagnosis was realized
      with CT-Scan and magnetic resonance imaging. In both cases removal of the cyst
      provided relief. The pathogenesis of the presence of epidural gas is discussed
      and the literature reviewed.

PMID- 7723926
TI  - [Spinal cord injuries caused by extraspinal gunshot. A historical, experimental
      and therapeutic approach].
AB  - A careful study of all clinical observations reported by various authors during
      one century teaches us that spinal cord wounds caused by a missile path away from
      the spine have always had vague and mysterious mechanisms. We have simulate shots
      near the cervical spine included in gelatin and we have shot at pigs weighing 100
      kilograms, previously anaesthetized and bio-instrumented according to J. Breteau
      methodology. So, we have been able to reproduce medullary wounds by shooting in
      the nape of the neck, away from the cervical spine. The knowledge of all
      mechanisms of balistic wounds, the analysis of the results obtained and a
      histological examination of wounded medulla leads us to the conclusion that this
      type of medullary wound distance from the spinal cord, is not specific and that,
      in fact, the missile causes an ordinary medullary contusion. While waiting for
      forthcoming medicinal progress, a management of treatment is suggested.

PMID- 7723927
TI  - [Anterior osteosynthesis of the cervical spine by phusiline bioresorbable screws
      and plates. Initial results apropos of 5 cases].
AB  - The authors have designed a biocompatible and bioresorbable plate (1) in
      Phusilines* for anterior cervical interbody stabilization. Phusilines* are
      polymer of alpha hydroxyacid (poly lactic acid), and their in vivo degradation
      (in lactic acid and via the Krebs circle, in water and carbon dioxide), is
      complete within 18 months. Screws are available in the same material. Phusilines*
      are radiotransparent and do not interfere with MRI. The size and shape of the
      plate have been determined with three dimensional computed tomography, their
      thickness and their molecular weight and chemical structure have been determined
      to obtain the best compromise in mechanical properties and time of resorption.
      Biomechanical studies have been performed in cadaver, and have showed a good
      quality of the osteosynthesis. Five patients with anterior cervical disco
      ligamental instability were operated on according the french law of bioethic
      (Huriet Law). In these five cases the operation was performed via antero lateral
      approach, and it consisted in a interbody xenograft with Surgibone (2) and
      interbody osteosynthesis with a plate and four screws of 16 mm of length and 4 mm
      of diameter. Clinical and radiological examinations were realised during 18
      months. In all cases, clinical results in rachialgia and neurological signs were
      excellent, in four case the tolerance was excellent, in a case inflammatory
      phenomens were observed the 8th and the 14th month successfully treated with non
      steroid anti-inflammatories. Anatomical results were excellent in two cases, good
      in two cases and incomplete in one case. Reasons of these incomplete results are
      discussed. These preliminary results are sufficient to continue these
      implantations.

PMID- 7723928
TI  - Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease.
AB  - In a double-blind, placebo study, acetyl-L-carnitine was administered to 7
      probable Alzheimer's disease patients who were then compared by clinical and 31P
      magnetic resonance spectroscopic measures to 5 placebo-treated probable AD
      patients and 21 age-matched healthy controls over the course of 1 year. Compared
      to AD patients on placebo, acetyl-L-carnitine-treated patients showed
      significantly less deterioration in their Mini-Mental Status and Alzheimer's
      Disease Assessment Scale test scores. Furthermore, the decrease in
      phosphomonoester levels observed in both the acetyl-L-carnitine and placebo AD
      groups at entry was normalized in the acetyl-L-carnitine-treated but not in the
      placebo-treated patients. Similar normalization of high-energy phosphate levels
      was observed in the acetyl-L-carnitine-treated but not in the placebo-treated
      patients. This is the first direct in vivo demonstration of a beneficial effect
      of a drug on both clinical and CNS neurochemical parameters in AD.

PMID- 7723929
TI  - Food restriction delays the age-related increase in GFAP mRNA in rat
      hypothalamus.
AB  - Astrogliosis with advancing age is correlated with increased expression of glial
      fibrillary acidic protein (GFAP). Hypothalamic GFAP mRNA prevalence was
      determined in male F344 rats of different ages that were fed ad lib (AL) and
      compared with that of rats that were food-restricted (FR) to 60% of AL levels.
      Hypothalamic GFAP mRNA increased 3-fold at 24 to 25 months in AL rats compared
      with 3 and 6 month groups. There were no differences in GFAP mRNA levels between
      AL and FR rats from 3 to 18 months. However, GFAP mRNA was significantly lower in
      FR than in AL rats at 24 to 25 months; FR rats reached the level of GFAP mRNA in
      24 to 25 months AL rats by 33 months. Hypothalamic glutamine synthetase mRNA also
      increased with age in both dietary groups but did not differ between dietary
      groups at any age. The observation that FR delays the increased expression of
      GFAP in the hypothalamus during aging lends support to the hypothesis that
      upregulation of GFAP mRNA is a biomarker of brain aging.

PMID- 7723931
TI  - Schmitt neurological sciences symposium: the cytoskeleton in Alzheimer's disease.

PMID- 7723930
TI  - No vasopressin cell loss in the human hypothalamus in aging and Alzheimer's
      disease.
AB  - The total number of immunocytochemically identified vasopressin (AVP) cells was
      determined morphometrically in the paraventricular (PVN) and dorsolateral part of
      the supraoptic nucleus (dl-SON) of the human hypothalamus in 30 subjects ranging
      in age from 15 to 97 years, including 10 Alzheimer's disease (AD) patients. The
      aim of the present study was to test the hypothesis that the increased activity
      of AVP neurons reported earlier is accompanied by an absence of cell loss in
      these nuclei in senescence and AD. The results show that numbers of
      immunoreactive AVP cells in the PVN and dl-SON do not decline during aging or in
      AD. During aging, the number of neurons expressing AVP even increased in the PVN
      of control subjects. The nuclear diameter of the AVP cells in the PVN and dl-SON
      showed an increase in old AD patients. It is concluded that no cell loss occurs
      in the AVP cell population in the PVN and dl-SON during aging and in AD, and that
      AVP expression increases in the PVN during normal aging, but not in AD.

PMID- 7723932
TI  - Decreased phospholipase C-beta immunoreactivity, phosphoinositide metabolism, and
      protein kinase C activation in senescent F-344 rat brain.
AB  - Phosphoinositide metabolism, phospholipase C immunoreactivity, and protein kinase
      C translocation were measured in brain slices of 6- and 24-month-old F-344 rats.
      Basal phosphoinositide labeling and accumulation of [3H]inositol phosphates were
      reduced in the 24-month-old rats. The cholinergic agonist, carbachol, induced
      lower net accumulations of inositol phosphates in striatal, hippocampal, and
      cortical slices of the aged rats. The dose-response curve for carbachol showed a
      significantly lower maximal response in the striatum of senescent rats, whereas
      the time course of [3H]inositol incorporation into inositol metabolites and the
      accumulation of free [3H]inositol in tissues from young and old animals were not
      different. Quantitative analyses showed marked reductions in endogenous brain
      levels of the phosphoinositides and in phospholipase C-beta 1 immunoreactivity,
      but no marked reductions in endogenous brain levels of the phosphoinositides and
      in phospholipase C-beta 1 immunoreactivity, but no changes in phospholipase C
      gamma levels in aged animals. Moreover, basal protein kinase C activity and
      carbachol-mediated translocation of the enzyme were significantly reduced in the
      cerebral cortex of the senescent animals. These findings imply that aging is
      associated with alterations in the brain content, metabolism, and activity of
      phosphoinositide-derived second messengers in the F-344 rat brain.

PMID- 7723933
TI  - Age-related changes in parvalbumin- and GABA-immunoreactive cells in the rat
      septum.
AB  - The calcium binding protein parvalbumin is present in GABAergic neurons of the
      medial septum-diagonal band of Broca (MS-DBB) region that project to the
      hippocampal formation. We examined the distribution pattern, the number, and the
      morphological features of the parvalbumin-containing cells (parv+) in the MS-DBB
      region of 2- to 3-, 8- to 9-, 15- to 16-, and 26- to 27-month-old Sprague-Dawley
      rats. A significant reduction in the number of parv+ cells was observed as a
      function of age. The mean somal area of the parv+ cells was significantly reduced
      in the 26- to 27-month-old rats. A significant reduction in the number of parv+
      cells was also observed in the 26- to 27-month-old rats in the cingulate cortex,
      but not in the striatum or the hippocampal formation. No significant age-related
      changes were observed in the number of the GABA-immunoreactive cells in the MS
      DBB region nor in the cingulate cortex. In conclusion, there is an age-related
      decrease in the number of parv+ cells, with no change in the number of GABA
      immunoreactive cells in the MS-DBB region of the rat. Because GABA and
      parvalbumin are colocalized in the MS-DBB neurons, the results suggest that the
      level of parvalbumin is decreased, but that the cells are not lost.

PMID- 7723934
TI  - Importance of forebrain cholinergic and GABAergic systems to the age-related
      deficits in water maze performance of rats.
AB  - The present study investigated the performance of rats at 3-4 months and 21
      months of age in the Morris water maze and correlated age-related cognitive
      deficits with changes in both cholinergic and GABAergic systems in the frontal
      cortex. The older rats were divided into two groups, unimpaired old and impaired
      old according to their ability to find a hidden submerged platform in the water
      maze, for electrophysiological, neurochemical, and morphological studies. The
      firing rate of frontal cortical neurones was recorded from the motor area of the
      frontal cortex under urethane anaesthesia and was found to be significantly
      slower in the two aged groups of rats compared to the young rats, but there were
      no differences between the two aged groups. The sensitivity of frontal cortex
      neurones of the impaired and unimpaired old age groups to ACh and to carbachol
      was significantly lower than that of the young group, but there were no
      differences between the two old age groups. In contrast, sensitivity of frontal
      cortex neurones to bicuculline was significantly higher in the aged rats compared
      with the young rats and was significantly greater in the impaired old rats than
      in the unimpaired old rats. The sensitivity of cortical neurones to glutamate was
      unaffected by age. There were also significant correlations between the
      percentages of cortical neurones responding to ACh and bicuculline and different
      parameters of water maze acquisition during days 7-8, but not during days 2-3,
      when spatial learning had not begun, and days 13-14, when spatial learning was
      complete. Biochemical and morphological analyses did not show any significant
      differences in ChAT activity and AChE-positive fibre density in the
      frontoparietal cortices of the three groups of rats. The results demonstrate that
      the learning deficit observed in old age rats cannot be adequately explained
      solely by a reduction in cholinergic receptor sensitivity and that an age-related
      increase in GABAergic tone may be a more important determinant of cognitive
      impairment.

PMID- 7723935
TI  - Neurotoxicity of A beta amyloid protein in vitro is not altered by calcium
      channel blockade.
AB  - In cortical cultures, A beta protein destabilizes calcium homeostasis, but direct
      neurotoxicity of A beta is not observed. In hippocampal cultures, we and others
      find treatment with A beta protein decreases neuronal survival, but the mechanism
      of neurotoxicity is unknown. We have used low-density, serum-free cultures of
      hippocampal neurons to determine whether the neurotoxicity of A beta protein in
      vitro can be altered by voltage- or ligand-gated calcium channel antagonists or
      cyclic nucleotides. In these cultures, neither omega-conotoxin, nifedipine,
      verapamil, APV, nor MK-801 altered the survival of neurons exposed to synthetic A
      beta 1-40. The N-channel antagonist diltiazem decreased A beta 1-40 toxicity
      repeatedly, but slightly, perhaps by indirectly contributing to increased
      neuronal viability. Treatment of cultures with dibutyryl cAMP, 8-bromo cAMP,
      dibutyryl cGMP, and 8-bromo cGMP also failed to alter A beta toxicity. Thus, the
      toxicity of beta protein in low-density hippocampal cultures was not directly
      altered either by calcium channel blockers or by the addition of cyclic
      nucleotides.

PMID- 7723936
TI  - Studies on lipid peroxidation and protein oxidation in the aging brain.
AB  - Lipid peroxidation (LP) and protein oxidation (PO) were investigated in
      hippocampus and frontal cortex homogenates from young (5 months), mature (13
      months) and old (24 months) Wistar rats and young (5 months) and old (24 months)
      Brown Norway rats. LP and PO were determined in basal conditions and after
      incubation without iron (spontaneous condition) or with iron (stimulated
      condition). LP was measured as HPLC-assayed malondialdehyde (MDA) and PO as
      protein carbonyl (CO) content. Brain homogenates formed considerable amounts of
      MDA and CO spontaneously and, to an even greater extent, in the presence of Fe2+.
      Old rats showed greater iron-stimulated LP in the cortex than young rats, but the
      difference was not significant. Basal (but not spontaneous or stimulated) PO was
      significantly increased (19%) in the hippocampus of old compared to young rats.
      This study does not confirm the age-related increase in LP reported in the
      literature and only partially confirms the findings concerning PO.

PMID- 7723937
TI  - Increases of glial fibrillary acidic protein in the aging female mouse brain.
AB  - Age-related increases of the astrocyte marker, glial fibrillary acidic protein
      (GFAP), were further resolved by in situ hybridization and immunocytochemistry in
      female C57BL/6J mice. The age groups represented the major stages of reproductive
      aging: young (5 months), middle-age (18 months), and old (23 and 26 months). GFAP
      mRNA and protein showed generalized increases in old mice. Major white fiber
      tracts, such as the corpus callosum, fimbria, stria terminalis, and optic tract,
      showed increased GFAP immunostaining and mRNA. Gray matter showed robust > or =
      twofold increases in GFAP mRNA with age, especially in the thalamus and
      hypothalamus, areas that expressed little GFAP in the young. These generalized
      age-related increases of GFAP in many brain regions imply the existence of a
      widespread stimulus for increased activity of astrocytes during aging.

PMID- 7723938
TI  - Age-dependent accumulation of advanced glycosylation end products in human
      neurons.
AB  - Glucose can react nonenzymatically with free amino groups on proteins and form
      advanced glycosylation end-products (AGEPs), that have been previously isolated
      and characterised in aging human connective tissues. In this study, we used
      immunocytochemistry to examine the distribution of AGEPs in the aging human
      brain. Our findings show that the pyramidal neurons selectively accumulate AGEP
      containing vesicles in an age-dependent manner. In addition, our results
      demonstrate that AGEPs accumulate in the same type of neuron that degenerates in
      Alzheimer's disease.

PMID- 7723939
TI  - Age-related alterations in tanycytes of the mediobasal hypothalamus of the male
      rat.
AB  - By means of semiquantitative immunocytochemistry, possible age-related changes in
      dopamine and cyclic AMP-regulated phosphoprotein mr 32 (DARPP-32) and glial
      fibrillary acidic protein (GFAP) immunoreactivities (IR) were investigated in
      tanycytes of the arcuate nucleus. These two markers showed opposite changes
      during aging. DARPP-32 IR decreased by around 70%, whereas GFAP IR increased by
      around 300% in 24-month-old vs. 3-month-old rats. These changes were accompanied
      by a progressive loss in the number of tanycytes, measured by counting of their
      long processes in the arcuate nucleus. No significant age-related change was
      observed either in GFAP IR in astrocytic populations of the mediobasal
      hypothalamus or in tyrosine hydroxylase IR in dopaminergic neurons of the dorsal
      arcuate nucleus. These observations indicate that the tanycytic population of the
      arcuate nucleus undergoes important modifications during aging, which include
      cell loss, impairment in the intracellular signalling cascade linked to DARPP-32,
      and hypertrophy. These changes may be related to the alterations in the
      neuroendocrine systems known to occur during aging.

PMID- 7723940
TI  - Relationship of hematological variables to learning performance in aged Fischer
      344 rats.
AB  - The relationship between hematological variables and the ability to perform
      behaviorally in two learning tests was evaluated in male F344 rats aged 22-24
      months. Rats were screened for ability to meet criterion for learning one-way
      active avoidance in a straight runway task. Rats failing to meet criterion were
      given no further testing and were assigned to Group 1 (G1). Rats meeting
      criterion were tested in a 14-unit T-maze (2 days, 10 trials/day). Failure to
      negotiate the T-maze within 600 s on any three trials resulted in assignment to
      Group 2 (G2) with no further testing. Rats successfully completing both tasks
      constituted Group 3 (G3). Trunk blood was collected following behavioral testing
      and was assayed to determine red blood cell count (RBC), hematocrit (HCT),
      hemoglobin (HGB), mean corpuscular volume (MCV), mean corpuscular hemoglobin
      (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count
      (WBC), bands (BND), polymorphs (POLY), lymphocytes (LYM), monocytes (MON), and
      eosinophils (EOS). The combined G1/G2 group had significantly lower RBC, HCT,
      HGB, and EOS but significantly higher MCV and MCH than G3 rats. Correlation
      analysis revealed a positive relationship of group membership (i.e., learning
      test completion) to RBC, HCT, HGB, and EOS, but a negative correlation of group
      membership to MCH. No significant correlation emerged between any hematological
      characteristic and performance in either behavioral task. These results suggest
      that a simple blood test to determine HCT may be a useful screen for removal of
      moribund rats from aging studies attempting to control for effects of health on
      behavioral performance in rodent models.

PMID- 7723941
TI  - Adrenergic and serotonergic receptors in aged monkey neocortex.
AB  - Autoradiography was employed to compare the distribution and density of
      adrenergic (alpha 1, alpha 2, and beta) and serotonergic (5-HT1 and 5-HT2)
      receptors in the neocortex of young adult (3 to 10 years of age) and aged (> 20
      years of age) rhesus monkeys. The age-related changes in the density of
      adrenergic and serotonergic sites were area and layer specific. A decrease in the
      density of alpha 1 receptors occurred only in the superficial layers of the
      somatosensory cortex, whereas the density of alpha 2 receptors declined in layer
      I of the prefrontal cortex and in most layers of the motor and somatosensory
      regions. The increase in beta receptors was largely confined to the deep layers
      of the motor and somatosensory areas. The density of 5-HT1 sites decreased in
      most layers of the somatosensory cortex, while 5-HT2 receptors declined in the
      deep layers of the motor cortex and middle strata of the visual cortex. Overall,
      adrenergic and serotonergic receptors were least affected in the prefrontal
      cortex and most compromised in the motor and somatosensory cortex of aged
      primates.

PMID- 7723942
TI  - Whither clinical research?

PMID- 7723943
TI  - Neuroreality I. Dedicated demolition of the Decade of the Brain: the genuine
      threat to neurologic research from the animal radical right. The American Academy
      of Neurology Animal Studies Subcommittee.

PMID- 7723944
TI  - Age-associated memory impairment: sorting out the controversies.

PMID- 7723945
TI  - Beyond DNR: fine-tuning end-of-life decision-making.

PMID- 7723946
TI  - Binswanger's disease--revisited.

PMID- 7723947
TI  - Do-not-resuscitate orders in acute stroke.
AB  - Although the general guidelines for do-not-resuscitate (DNR) orders apply to
      acute stroke patients, few data are available to aid decision-making. With a view
      to developing specific guidelines for use in patients with acute stroke, we
      decided to evaluate the clinical factors associated with DNR orders at our
      university teaching hospital. We prospectively studied 450 consecutive patients
      with acute hemispheric strokes (237 men and 213 women, mean age 75 +/- 12 years).
      Thirty-six patients (8%) had intracerebral hemorrhage (ICH) and 414 (92%) had
      ischemic strokes. Overall inhospital mortality was 26%. DNR status was given to
      31% of all patients at some time during their admission (83% of those died). DNR
      decision-making was closely associated with the severity of the neurologic
      deficit (Canadian Neurological Scale score < or = 5); the patient's incapacity
      for informed DNR decision-making; age (> 60 years); and devastating ICH
      unsuitable for surgery (p < 0.001). Fifty-three percent of DNR orders were given
      on admission (first 24 hours of the hospital stay), 35% during the first week of
      the hospital stay, due to brain damage, and 12% at any time between days 8 and 44
      due to systemic complications. Once DNR status was given, 53% of patients
      continued to receive normal nutrition and 60% still received medical or surgical
      treatment. Although the current practice of DNR orders in patients with acute
      stroke is generally satisfactory, some criteria (eg, age and operable ICH) need
      revision.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7723948
TI  - Elective intubation for neurologic deterioration after stroke.
AB  - OBJECTIVE: To provide data to guide physicians and family when deciding whether a
      patient should be electively intubated after ischemic stroke. DESIGN: Chart
      review and patient interview. Clinical course, neurologic outcome, and financial
      and psychosocial effect of the decision to intubate were determined. SETTING:
      Neurology/Neurosurgery critical care unit. PATIENTS: Of our last 250 acute
      carotid territory ischemic stroke cases, we found 20 patients (8%) who were
      electively intubated, after CT and neurologic assessment, for neurologic
      deterioration. INTERVENTIONS: All patients received standard medical therapy.
      RESULTS: Intubation occurred 3 hours to 7 days (mean, 41 hours) after the onset
      of symptoms; six of 20 patients required intubation within the first 6 hours.
      Once clinical deterioration began, 10 of 20 patients required intubation within 1
      hour. Six of 20 patients were discharged alive; two subsequently died, one is
      mostly dependent, two became mostly independent (one of these had a
      hemicraniectomy and is still improving, and the other died of an intercurrent
      illness 4 years after her stroke), and one is totally independent. The four
      "good" outcome survivors were distinguished by higher Glasgow Coma Scale scores
      (9.2 versus 5.9), and extubation was usually possible within 72 hours. For
      nonsurvivors, mean hospitalization after intubation was 6.4 days. In survivors,
      the monthly uninsured cost was $0 to $2,000, and caregivers experienced moderate
      stress. The same decision would be repeated by 76% of caregivers; 53% of
      caregivers would want intubation for themselves. CONCLUSIONS: Satisfactory
      outcome is possible in the 8% of ischemic stroke patients requiring elective
      intubation. Possible predictors of good outcome include less severe depression of
      consciousness at the time of intubation, extubation within 3 days, and
      hemicraniectomy. In retrospect, most families would repeat the decision to
      intubate. Further study in more patients of the cost/benefit of cerebral
      resuscitation after stroke is greatly needed.

PMID- 7723949
TI  - Tremor and longevity in relatives of patients with Parkinson's disease, essential
      tremor, and control subjects.
AB  - To study the relation between essential tremor (ET) and Parkinson's disease (PD),
      we compared the frequency of familial tremor in relatives of patients with PD (N
      = 391), ET (N = 140), and the combination of ET and PD (N = 125) with the
      frequency in patients with progressive supranuclear palsy (PSP) (N = 99) and
      normal age-matched controls (N = 104). Tremor was present in 96 (5.1%) of 1,874
      parents and siblings of patients with PD, 152 of 650 (23.4%) relatives of
      patients with ET, 91 (20.7%) of 439 relatives of patients with ET-PD, 12 of 462
      (2.6%) relatives of patients with PSP, and 10 of 448 (2.2%) relatives of normal
      controls. The high frequency of familial tremor among relatives of patients with
      PD, and especially those with the ET-PD combination, compared with relatives of
      patients with PSP or of normal controls suggests that there is an association of
      PD and familial tremor. Since the most common form of familial tremor is ET, our
      study provides support for the notion that ET and PD are pathogenetically
      related. We also found that parents with tremor lived on the average 9.2 years
      longer than those without tremor. The association of familial tremor with
      significantly increased longevity suggests that familial tremor confers some anti
      aging influence. Alternatively, tremor may be a simple byproduct of the aging
      process.

PMID- 7723950
TI  - Clinical features and pathogenesis of intracerebral hemorrhage after rt-PA and
      heparin therapy for acute myocardial infarction: the Thrombolysis in Myocardial
      Infarction (TIMI) II Pilot and Randomized Clinical Trial combined experience.
AB  - Parenchymatous intracerebral hemorrhage (ICH) is a serious, infrequent
      complication of thrombolytic therapy for acute myocardial infarction. We studied
      the clinical and radiologic features, manner of presentation, associated factors,
      and temporal course in 23 patients with ICH associated with 150 mg or 100 mg
      recombinant tissue-type plasminogen activator (rt-PA) and heparin therapy for
      acute myocardial infarction in the Thrombolysis in Myocardial Infarction (TIMI)
      II Pilot and Randomized Clinical Trial. In TIMI II, 13 of the 23 ICH patients
      developed or maintained systolic blood pressure > or = 160 mm Hg or diastolic
      blood pressure > or = 90 mm Hg during the rt-PA infusion and before the onset of
      neurologic symptoms. Six patients (26%) had life-threatening ventricular
      arrhythmias, five before onset of neurologic symptoms. A decreased level of
      consciousness was the earliest neurologic abnormality in 15 (65%) and the most
      common initial physical finding (in 19, or 82%). Onset was usually gradual (70%),
      but time to maximal deficit was frequently (61%) within 6 hours of onset. The
      locations of the primary ICH sites were lobar in 16 (70%), thalamic in four
      (17%), and brainstem-cerebellum in three (13%), but the putamen was never the
      primary site. Multiple lobar hemorrhages occurred in six cases (26%). The timing
      and size of ICH was similar among patients treated with 150 mg rt-PA and 100 mg
      rt-PA. Brain CT demonstrated an arteriovenous malformation in one case. Four
      patients had hypofibrinogenemia, which was profound in three patients. Pathologic
      findings were available for five patients. Of these, three patients had cerebral
      amyloid angiopathy, and one had hemorrhagic transformation of an ischemic
      cerebral infarction found at autopsy. We conclude that ICH following rt-PA and
      heparin therapy for acute myocardial infarction presents as a distinctive
      clinical syndrome. Intracerebral bleeding after combined thrombolytic and
      antithrombotic therapy may be associated with cerebral amyloid angiopathy and
      other vascular lesions. Acute or persistent hypertension before or during rt-PA
      infusion, life-threatening ventricular arrhythmias, and hypofibrinogenemia,
      either alone or in combination, may play roles in some cases. Care should be
      exercised when considering thrombolytic therapy for patients with risk factors
      for ICH.

PMID- 7723951
TI  - Race-ethnic differences in stroke risk factors among hospitalized patients with
      cerebral infarction: the Northern Manhattan Stroke Study.
AB  - African-Americans have an unexplained increased incidence and mortality from
      stroke compared with whites, and little is known about stroke in Hispanics. To
      investigate cross-sectional differences in sociodemographic and stroke risk
      factors, we prospectively evaluated 430 patients hospitalized for acute ischemic
      stroke (black 35%. Hispanic 46%, white 19%) over the age of 39 from Northern
      Manhattan. Blacks and Hispanics were younger than whites (mean ages, blacks 70,
      Hispanics 67, whites 80; p < 0.001) and were more likely to have less than 12
      years of education than whites. Hypertension was more prevalent in blacks and
      Hispanics with stroke than whites (blacks 76%, Hispanics 79%, whites 63%; p <
      0.05) and was often untreated in blacks. Left ventricular hypertrophy by ECG was
      more frequent in blacks (blacks 20%, whites 9%; p = 0.02). History of cardiac
      disease (atrial fibrillation, myocardial infarction, angina, and congestive heart
      failure) was less prevalent in both blacks and Hispanics. Black women were
      significantly more obese than white women (mean Quetelet Index percent, blacks
      3.9%, whites 3.6%; p < 0.05). Heavy alcohol use was more often reported by blacks
      and Hispanics; cigarette smoking was increased only in blacks. Moreover, blacks
      were less likely to have visited a physician 1 year after their stroke (blacks
      85%, whites 98%; p < 0.05), and Hispanics less often lived alone compared with
      whites. These cross-sectional differences suggest that the burden of stroke risk
      factors is increased in both blacks and Hispanics with stroke. Further studies
      controlling for stroke risk factors are needed to establish whether race
      ethnicity is an independent determinant of stroke risk.

PMID- 7723952
TI  - Persistent positive visual phenomena in migraine.
AB  - Ten patients with migraine developed persistent positive visual phenomena lasting
      months to years. The complaints were similar in their simplicity and involvement
      of the entire visual field and usually consisted of diffuse small particles such
      as TV static, snow, lines of ants, dots, and rain. Neurologic and ophthalmologic
      examinations were normal, and EEGs were normal in eight of eight patients tested.
      MRI was normal in all patients except one who had nonspecific biparietal white
      matter lesions and another with a small venous angioma. Treatment of this unusual
      complication of migraine was unsuccessful.

PMID- 7723953
TI  - Mortality and hallucinations in nursing home patients with advanced Parkinson's
      disease.
AB  - We monitored 11 patients with advanced Parkinson's disease (PD) who entered
      nursing homes over a 5-year period and assessed chronicity of nursing home care,
      mortality, and hallucinatory status. Two years after the original study's close,
      none of these patients had ever been discharged from the nursing homes and all
      were dead. The mortality rate among the nursing home patients was significantly
      greater than that in 22 community-dwelling subjects with PD who were matched for
      age, gender, and disease duration. Hallucinatory status was generally stable; 82%
      of patients had the same hallucinatory status (presence or absence) at the two
      assessments. Four subjects from the original community-dwelling control group
      entered nursing homes during the follow-up period. Whereas motor and intellectual
      impairment scores were similar between these patients and the remaining 18 in the
      community, the presence of hallucinations was significantly greater among
      patients transferred to nursing homes. The study demonstrates the permanency of
      nursing home placement in advanced PD and the high mortality associated with such
      placement. It also documents the chronicity of hallucinatory behavior in these
      patients with advanced PD and reinforces our previously reported observations on
      the relationship between hallucinations and placement in chronic-care facilities.

PMID- 7723954
TI  - The influence of depression on cognition in Parkinson's disease: a pattern of
      impairment distinguishable from Alzheimer's disease.
AB  - Conflicting reports about the effects of depression on cognition in Parkinson's
      disease (PD) are difficult to interpret because they are based on small sample
      sizes and confound depression with other variables. We found that a sample of 45
      PD patients with current depression was cognitively more impaired than a sample
      of 45 PD patients without current depression matched for age, education, gender,
      age at disease onset, disease duration, and disease severity. The domains of
      cognition impaired in the two PD groups (compared with 45 age-, education-, and
      gender-matched controls) overlapped considerably, but only the depressed PD group
      had impaired memory relative to the control group. Our comparison of 22 depressed
      PD patients and 22 Alzheimer's disease (AD) patients matched for over-all
      severity of cognitive impairment, age, education, and gender indicated that the
      depressed PD group performed significantly worse on visuoconstructive tasks and
      marginally worse on conceptualization tasks. In contrast, the AD group performed
      significantly worse than the depressed PD group on memory tasks. Together, our
      results suggest that depression has a negative impact on cognition (and, in
      particular, memory) in PD, and that the pattern of this cognitive impairment is
      distinguishable from that associated with AD.

PMID- 7723955
TI  - Genetic and biochemical normalization in female carriers of Duchenne muscular
      dystrophy: evidence for failure of dystrophin production in dystrophin-competent
      myonuclei.
AB  - We studied 19 symptomatic female carriers of the Duchenne muscular dystrophy
      (DMD) gene. Most of these dystrophinopathy patients had had an erroneous or
      ambiguous diagnosis prior to dystrophin immunofluorescence testing. We assessed
      clinical severity by a standardized protocol, measured X-chromosome inactivation
      patterns in blood and muscle DNA, and quantitated the dystrophin protein content
      of muscle. We found that patients could be separated into two groups: those
      showing equal numbers of normal and mutant dystrophin genes in peripheral blood
      DNA ("random" X-inactivation), and those showing preferential use of the mutant
      dystrophin gene ("skewed" X-inactivation). In the random X-inactivation carriers,
      the clinical phenotype ranged from asymptomatic to mild disability, the
      dystrophin content of muscle was > 60% of normal, and there were only minor
      histopathologic changes. In the skewed X-inactivation patients, clinical
      manifestations ranged from mild to severe, but the patients with mild disease
      were young (5 to 10 years old). The low levels of dystrophin (< 30% on average)
      and the severe symptoms of the older patients suggested a poor prognosis for
      those with skewed X-inactivation, and they all showed morphologic changes of
      dystrophy. The random inactivation patients showed evidence of biochemical
      "normalization," with higher dystrophin content in muscle than predicted by the
      number of normal dystrophin genes. Seventy-nine percent of skewed X-inactivation
      patients (11/14) showed genetic "normalization," with proportionally more
      dystrophin-positive nuclei in muscle than in blood. In 65% of the skewed X
      inactivation patients, dystrophin was not produced by dystrophin-positive nuclei;
      an average of 20% of myofiber nuclei were genetically dystrophin-positive but did
      not produce stable dystrophin. Biochemical normalization seems to be the main
      mechanism for rescue of fibers from dystrophin deficiency in the random X
      inactivation patients. In the skewed X-inactivation patients, genetic
      normalization is active, but production failure of dystrophin by dystrophin
      normal nuclei may counteract any effect of biochemical normalization. In the
      skewed X-inactivation patients, the remodeling of the muscle through cycles of
      degeneration and regeneration led to threefold increase in the number of
      dystrophin-competent nuclei in muscle myofibers (3.3 +/- 4.6), while dystrophin
      content was on the average 1.5-fold less then expected (-1.54 +/- 3.38). Our
      results permit more accurate prognistic assessment of isolated female
      dystrophinopathy patients and provide important data with which to estimate the
      potential effect of gene delivery (gene therapy) in DMD.

PMID- 7723956
TI  - Ultrasound findings in carotid artery dissection: analysis of 43 patients.
AB  - BACKGROUND AND PURPOSE: To analyze the value of ultrasound for early diagnosis
      and follow-up of internal carotid artery dissection. METHODS: The carotid
      arteries were evaluated in 43 consecutive patients using extracranial and
      transcranial pulsed-wave Doppler and duplex sonography. RESULTS: Ultrasound
      examination was performed, on average, 7.7 days after the first symptoms. The
      dissections subsequently were verified by MRI (16 patients), angiography (13
      patients), or both (14 patients) on average 4.4 days later. The overall
      sensitivity of the combined examination was 95% (93% for extracranial Doppler,
      86% for transcranial Doppler, and 79% for duplex sonography). All three methods
      detected occlusions or high-grade stenoses in 100% of patients and moderate- or
      low-grade stenoses in 80% (combined methods), 70% (extracranial Doppler), 40%
      (transcranial Doppler), and 20% (duplex) of the patients. The findings in 33
      patients with an occlusion or high-grade stenosis according to neuroradiology
      were as follows: absent flow signal in the internal carotid artery (100%) and
      biphasic (stump) flow in its bulb (86%), high-resistance flow pattern of the
      ipsilateral common carotid artery (91%), signs of collateral flow across the
      circle of Willis (97%), and low flow in the middle cerebral artery (79%) on
      transcranial insonation. In seven patients, a moderate stenosis of the high
      cervical carotid segment was found because of a retromandibular high-velocity
      signal. In five of them this was the only abnormal finding. Duplex examination
      was helpful because it confirmed absent internal carotid artery flow or stump
      flow in the case of occlusion or high-grade stenosis (100%) and excluded an
      atherosclerotic origin by demonstrating a patent bulb (100%) and the absence of
      plaques (95%). Follow-up studies showed recanalization in 63% of patients,
      occurring at variable intervals. Occlusion persisted in 37%. CONCLUSIONS:
      Ultrasound performed within the first weeks can corroborate a clinically
      suspected carotid dissection in up to 95% of patients. Repetitive follow-up
      studies in most cases are sufficient to monitor evolution.

PMID- 7723957
TI  - Autosomal dominant distal spinal muscular atrophy in four generations.
AB  - Distal spinal muscular atrophy is a rare lower motor neuron disorder that may be
      difficult to distinguish clinically from type II Charcot-Marie-Tooth disease. We
      report on clinical and pathologic findings in 13 members of a four-generation
      extended family with autosomal dominant distal spinal muscular atrophy. The
      patients developed a slowly progressive lower motor neuron disorder involving
      mainly the distal lower extremities; onset was from the second to fourth decades.
      Electromyography and muscle biopsy findings were indicative of motor denervation.
      Combined silver/cholinesterase/immunocytochemical staining of intramuscular nerve
      revealed abundant collateral axonal branching in mild disease but marked loss of
      terminal motor endplate innervation in the more severe state, suggesting
      decreased growth of motor axon collaterals with disease progression. Multipoint
      DNA linkage analysis showed that this family's disorder is not linked to the
      chromosome 5q11.2-13.3 spinal muscular atrophy locus.

PMID- 7723958
TI  - Dementia in Parkinson's disease: a population-based study in ambulatory and
      institutionalized individuals.
AB  - We examined the frequency of dementia and depressive symptomatology in 60
      Parkinson's disease (PD) patients, identified in a large representative sample of
      the population, aged 65 years and older, living at home or in institutions in
      Gironde, France. Dementia, diagnosed according to DSM-III-R criteria, was present
      in 17.6%, and depressive symptomatology, assessed by the Center for Epidemiologic
      Studies-Depression Scale, was present in 32.7%. The frequency of dementia in PD
      increased strongly with age and was higher in institutionalized PD patients than
      in those living at home. PD was significantly associated with dementia for
      individuals living at home (odds ratio = 8.2, adjusted for age and symptoms of
      depression.

PMID- 7723959
TI  - Incidental Lewy body disease in a patient with REM sleep behavior disorder.
AB  - We studied an 84-year-old man with a 20-year history of nocturnal violent
      behavior during sleep, but no other clinically evident neuropsychiatric
      disorders. Polysomnographic investigations confirmed that he suffered from REM
      sleep behavior disorder (RBD). Histopathologic examination revealed he had Lewy
      body disease with a marked decrease of pigmented neurons in the locus ceruleus
      and substantia nigra. These histologic findings represent the first documented
      evidence of a loss of brainstem monoaminergic neurons in clinically idiopathic
      RBD and suggest that Lewy body disease might provide an explanation for
      idiopathic RBD in the aged.

PMID- 7723960
TI  - Botulinum toxin A for spasticity, muscle spasms, and rigidity.
AB  - We studied the effects of botulinum toxin A in 12 patients with spasticity and in
      eight patients with rigidity. The study design was a double-blind, placebo
      controlled crossover trial with botulinum toxin A versus saline. Using the
      Ashworth Scale for spasticity and the Unified Parkinson's Disease Rating Scale
      for rigidity, we gave the patients a tone grade before and 2 weeks after
      treatment. Improvement in tone by two grades or more was considered clinically
      significant. In the spasticity group, botulinum toxin A reduced the tone of all
      patients significantly, improved functionality and nursing care in eight of 12
      patients, and alleviated painful spasms in five of five patients. In the rigidity
      group, muscle tone was decreased in seven of eight patients, functionality
      improved in four of seven, and joint and muscle pain decreased in four of five.
      We conclude that botulinum toxin A is effective against the disabling effects of
      spasticity and rigidity. The treatment was well tolerated.

PMID- 7723961
TI  - Identifying multiple sclerosis patients with mild or global cognitive impairment
      using the Screening Examination for Cognitive Impairment (SEFCI).
AB  - Cognitive impairment affects 40 to 70% of patients with multiple sclerosis (MS),
      but its occurrence cannot be predicted from knowledge of the individual patient's
      age, level of physical disability, duration of disease, disease type, or
      performance on standard mental status examinations. To evaluate the usefulness of
      a brief screening battery, the Screening Examination for Cognitive Impairment
      (SEFCI), 103 community-dwelling MS patients and 32 healthy normal controls
      received the SEFCI and a 2-hour battery of other neuropsychological tests chosen
      for their sensitivity to the cognitive impairments most often observed in MS.
      Performance on the SEFCI correctly identified 86% of the patients with impairment
      on any of the 11 measures from the longer battery, 100% of the patients with
      impairments in at least three cognitive domains, and 90% of the patients without
      cognitive impairment. Because the SEFCI is sensitive, specific, and easily
      administered and scored, it should aid the physician in deciding whether to refer
      an MS patient for a complete evaluation.

PMID- 7723962
TI  - A population-based study of neonatal seizures in Fayette County, Kentucky.
AB  - This population-based, retrospective cohort study of neonatal seizures included
      all neonates born to residents of Fayette County, Kentucky, from 1985 to 1989. We
      ascertained potential cases by computer search of hospital-based medical record
      systems, Kentucky Center for Health Statistics birth certificate data files, and
      National Center for Health Statistics multiple-cause-of-death mortality data
      files. Medical records for potential cases were abstracted, and relevant portions
      were reviewed independently by three neurologists using prospectively determined
      case-selection criteria. Seizures occurred in 58 of 16,428 neonates (3.5/1,000
      live births). An additional 15 neonates had possible seizures, for a combined
      risk of 4.4/1,000 live births. Neonatal seizure risk varied inversely with birth
      weight: 57.5/1,000 live births among very low birth weight infants (< 1,500
      grams) compared with 4.4/1,000 for infants with moderately low birth weight
      (1,500 to 2,499 grams), 2.8/1,000 for those with normal birth weight (2,500 to
      3,999 grams), and 2.0/1,000 for those with high birth weight (4,000 or more
      grams). Risk varied among the four hospitals in the county with obstetric units,
      the university hospital having the highest risk. Risk did not differ by race or
      gender. A Cox proportional hazards model confirmed the results of the simpler
      univariate analyses. Differences in birth weight of the subpopulations served by
      each hospital accounted for much but not all the differences in hospital-specific
      risk.

PMID- 7723963
TI  - Physiology of fatigue in amyotrophic lateral sclerosis.
AB  - We investigated the mechanisms of muscle fatigue in ALS. In the muscles of ALS
      patients and healthy control subjects, we examined (1) fatigue using measurements
      of muscle force, (2) energy metabolism using phosphorus-31 magnetic resonance
      spectroscopy, and (3) activation using neurophysiologic measures and MRI. During
      25 minutes of intermittent isometric exercise of the tibialis anterior muscle,
      both maximum voluntary and tetanic force declined more in patients than in
      controls, indicating greater fatigability in ALS. There was a similar decline of
      voluntary and tetanic force, suggesting that much of the fatigue was not central.
      Evoked compound muscle action potential amplitudes were preserved during exercise
      in both groups, indicating no failure of neuromuscular transmission; this result
      suggests that the source of fatigue was not at the neuromuscular junction or
      within the muscle membrane. In spite of greater fatigability, changes during
      exercise in energy metabolites and proton signal intensity tended to be less in
      ALS patients compared with controls, suggesting impaired muscular activation. We
      conclude that the greater muscle fatigue in ALS patients results from activation
      impairment, due in part to alterations distal to the muscle membrane.

PMID- 7723964
TI  - Prevalence of age-associated memory impairment in a randomly selected population
      from eastern Finland.
AB  - Aging has multiple effects on memory in normal subjects. However, information on
      the prevalence of age-associated memory impairment (AAMI) is scanty. We studied
      the prevalence of AAMI in a randomly selected population of 1,049 subjects aged
      60 to 78 years from eastern Finland. Research criteria proposed by the National
      Institute of Mental Health (NIMH) Work Group were applied. We calculated
      prevalence rates for AAMI by the inclusion criteria alone (subjective and
      objective memory impairment and no dementia) as well as by the inclusion and
      exclusion criteria (evidence of any neurologic or other medical disorder that
      could produce cognitive deterioration) for the total study population, for both
      sexes, and for four age groups (60 to 64, 65 to 69, 70 to 74, and 75 to 78
      years). Subjective memory impairment was present in 76.3% of the subjects.
      Prevalence rates for objective memory impairment ranged from 31.9 to 78.4% in
      individual tests. A total of 564 subjects (239 men, 325 women) were classified as
      having AAMI by the inclusion criteria alone, giving a prevalence rate of 53.8%
      (men, 57.4%; women, 51.3%). When we included the exclusion criteria, the
      prevalence of AAMI decreased to 38.4% (men, 42.5%; women, 35.7%). By both
      methods, age- and sex-specific prevalence rates were highest in the youngest
      group, aged 60 to 64 years, and lowest in the oldest group, aged 75 to 78 years.
      We conclude that the prevalence of AAMI, by the diagnostic criteria of the NIMH
      Work Group, is high in the elderly Finnish population.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7723965
TI  - Medial temporal lobe atrophy in an open population of very old persons:
      cognitive, brain atrophy, and sociomedical correlates.
AB  - Medial temporal lobe structures may be important for memory. We examined the
      cognitive, brain atrophy, and sociomedical correlates of medial temporal lobe
      atrophy (MTA) in 59 individuals (79.2 +/- 4.6 years old) randomly selected from a
      population-based study within strata of age and severity of clinically assessed
      DSM-III-R dementia (45 clinically normal and 14 mild/severely demented). MTA was
      qualitatively assessed on coronal T-1-weighted MRI. Thirty-three percent of the
      sample showed MTA, which was associated with dementia severity (p < 0.01), and
      cortical and white matter atrophy. MTA was not associated with age, education,
      sex, depressive symptoms, or presence of infarction. Controlling for age,
      education, and associated brain atrophy, those with MTA performed more poorly on
      a general test of cognitive function (the neuropsychological test component of
      the Cambridge Examination for Mental Disorders of the Elderly; p < 0.04) and its
      subtests of memory function (p < 0.02) and memory-related functions, including
      perception, fluency, and orientation (p < 0.05). In the clinically normal
      subsample, those with MTA performed more poorly on the memory function (p < 0.05)
      subtests. We conclude that MTA is common among very old persons, is associated
      with other brain abnormalities implicated in cognitive function, but may
      specifically contribute to memory dysfunction in the general population of very
      old persons.

PMID- 7723966
TI  - Stereotactic ventral pallidotomy for Parkinson's disease.
AB  - Eighteen patients with medically intractable Parkinson's disease that was
      characterized by bradykinesia, rigidity, and marked "on-off" fluctuations
      underwent stereotactic ventral pallidotomy under local anesthesia. Targeting was
      aided by anatomic coordinates derived from the MRI, intraoperative cell
      recordings, and electrical stimulation prior to lesioning. A nonsurgically
      treated group of seven similarly affected individuals was also followed.
      Assessment of motor function was made at baseline and at 3-month intervals for 1
      year. Following the lesioning, patients improved in bradykinesia, rigidity,
      resting tremor, and balance with resolution of medication-induced contralateral
      dyskinesia. When compared with preoperative baseline, all quantifiable test
      scores after surgery improved significantly with the patients off medications for
      12 hours: UPDRS by 65%, and CAPIT subtest scores on the contralateral limb by
      38.2% and the ipsilateral limb by 24.2%. Walk scores improved by 45%. Medication
      requirements were unchanged, but the patients who had had surgery were able to
      tolerate larger doses because of reduced dyskinesia. Ventral pallidotomy produces
      statistically significant reduction in parkinsonism and contralateral "on"
      dyskinesia without morbidity or mortality and with a short hospitalization in
      Parkinson's disease patients for whom medical therapy has failed.

PMID- 7723967
TI  - High levels of mitochondrial DNA with an unstable 260-bp duplication in a patient
      with a mitochondrial myopathy.
AB  - Other investigators reported the presence of low levels of a 260-bp heteroplasmic
      duplication of mitochondrial DNA in patients with mitochondrial DNA deletions and
      their asymptomatic mothers. In this study, we were not able to detect this
      polymorphism in 30 patients with mitochondrial DNA deletions, but the 260-bp
      duplication was detected in relatively high levels (32% in muscle) in a patient
      with a slowly progressive mitochondrial myopathy. The duplication was also
      present in cultured fibroblasts (10%) and in WBC (< 1%). Mitochondrial
      dysfunction in this patient was evidenced in muscle by the presence of ragged-red
      fibers and a partial decrease in cytochrome c oxidase activity. We also detected
      low levels of mitochondrial DNA harboring a triplication of the 260-bp region,
      indicating that this polymorphism is unstable. Taken together, our results
      suggest that an unstable 260-bp duplication, which includes important
      mitochondrial DNA cis-acting regulatory sequences, may be pathogenic per se, if
      present at high levels.

PMID- 7723968
TI  - Linkage of Miyoshi myopathy (distal autosomal recessive muscular dystrophy) locus
      to chromosome 2p12-14.
AB  - Miyoshi myopathy (MM) is a young-adult-onset, autosomal recessive distal muscular
      dystrophy initially affecting the plantar flexors. We analyzed 12 MM families,
      five with consanguineous marriage, for chromosomal linkage using polymorphic
      microsatellite DNA markers to map the MM gene. A significant lod score was
      obtained with the 2p12-14 locus D2S291 (Zmax = 15.3 at theta = 0). Two additional
      2p12-14 markers, D2S286 (Z = 10.7 at theta = 0) and D2S292 (Z = 7.2 at theta =
      0.05), also gave significant lod scores. These markers will be useful for
      diagnosis of symptomatic and presymptomatic patients, prenatal and carrier
      diagnosis of family members carrying MM, and ultimately identification of a gene
      responsible for MM.

PMID- 7723969
TI  - Neuropathy profile of diabetic patients in a pancreas transplantation program.
AB  - We describe the results of extensive neurologic evaluation of 290 patients with
      insulin-dependent diabetes mellitus who came to our institution as potential
      recipients of a pancreas transplant. Large nerve fibers were evaluated by motor
      and sensory nerve conduction, small sensory fibers by thermal sensation
      thresholds, vagal and vasomotor functions by cardiovascular reflexes, and
      sympathetic sudomotor fibers by silicone imprints and evaporimetry. A scored
      anamnesis revealed symptoms of neuropathy in 86% of patients; 94% had an abnormal
      neurologic examination. The most frequently abnormal measurements of motor
      conduction were the amplitude of the extensor digitorum brevis muscle action
      potential to peroneal nerve stimulation and the conduction velocity of peroneal
      and tibial nerves in more than 80% of patients. Sensory nerve action potentials
      were abnormal in 76% and the distal latency of the sural nerve in 91%. Heart rate
      variability with deep breathing and during a Valsalva's maneuver was abnormal in
      90% and 88%. Sudomotor function was reduced in 59% on the foot. Thermal
      sensitivity limen was above normal limits in 95% in the foot and 77% in the hand.
      Composite indexes of the degree of abnormality found for each type of function
      tested were correlated one with another, but were not predictive of results for
      any other test. The neuropathy of most patients was symmetric, involving to a
      similar degree motor, sensory, and autonomic nerves. Thus, diabetic neuropathy is
      very common and severe among patients who decide to be candidates for pancreas
      transplantation.

PMID- 7723970
TI  - The syndrome of frontal lobe epilepsy: characteristics and surgical management.
AB  - We reviewed the historical features, preoperative diagnostic evaluation,
      operative procedure, and surgical outcome in 16 patients with refractory frontal
      lobe epilepsy. Clinical expression of the epilepsy varied widely, particularly
      with respect to seizure characteristics, although high monthly seizure frequency
      and absence of a risk factor for epilepsy before age 5 occurred more often than
      in reported in temporal lobe epilepsy patients. Seizures often caused early
      bilateral movements, were brief, and lacked oroalimentary automatisms and a
      prolonged postictal state. Both the interictal and ictal scalp EEGs had
      relatively poor sensitivity and specificity and often either contained no
      epileptiform abnormalities or were misleading. MRI usually identified structural
      lesions when these were present, although it was negative in two patients with
      tumors. In the absence of an MRI lesion, intracranial EEG usually identified the
      area to be resected, although it too provided misleading information in one case.
      Surgical procedures consisted of focal resections with or without anterior corpus
      callosotomy, or of corpus callosotomy alone. Nearly all patients improved after
      surgery, with a majority (67%) becoming seizure-free (average follow-up, 46
      months). Preoperative seizure frequency correlated with seizure relief after
      surgery, as did age of seizure onset, whereas presence of tumor did not. We
      conclude that frontal lobe epilepsy warrants aggressive investigation and that
      surgical treatment often can be successful.

PMID- 7723971
TI  - Elevation of microtubule-associated protein tau in the cerebrospinal fluid of
      patients with Alzheimer's disease.
AB  - Currently, there is no biochemical marker clinically available to test for the
      presence of Alzheimer's disease (AD). Recent studies suggest that the core
      component of AD-associated neurofibrillary tangles (NFTs), the microtubule
      associated protein tau, might be present in CSF. This study focuses on
      establishing both the presence of tau in CSF and its potential utility in the
      diagnosis of AD. We obtained CSF from 181 individuals; 71 of these were diagnosed
      as having probable AD by NINCDS-ADRDA criteria. The remaining 110 individuals
      were divided into three groups: (1) age-matched demented non-AD patients (n =
      25), (2) neurologic controls (n = 59), and (3) other controls (n = 26). We
      developed a sensitive enzyme-linked immunosorbent tau assay using monoclonal
      antibodies prepared against recombinant human tau. We confirmed specificity of
      the antibodies by a combination of immunoprecipitation and immunoblot results. By
      this assay we measured that the AD population has a mean level of tau 50% greater
      than the non-AD dementia patients. Comparing AD patients with all other groups,
      the difference in tau levels as analyzed by one-way ANOVA is highly statistically
      significant (p < 0.001). Postmortem analysis of two AD patients with high levels
      of CSF tau revealed a high density of NFTs in the hippocampus. There was no
      significant correlation between tau and age in the non-AD groups. This study
      suggests that CSF tau is elevated in AD and might be a useful aid in antemortem
      diagnosis.

PMID- 7723972
TI  - Has spinocerebellar ataxia type 2 a distinct phenotype? Genetic and clinical
      study of an Italian family.
AB  - The gene for spinocerebellar ataxia type 2 (SCA2) is mapped to chromosome 12q23
      24.1. Using D12S79 and D12S105, we performed linkage analysis in nine individuals
      including six affected members of a four-generation family in which we excluded
      SCA1 by direct mutation analysis. We obtained a lod score = 2.37 at theta = 0.00
      for the compound haplotype. The clinical picture appeared homogeneous, showing
      the absence of corticospinal signs and the presence of peripheral neuropathy. The
      present study suggests that this SCA2 family is clinically different from most
      SCA1 families.

PMID- 7723973
TI  - Verbal memory impairment after right temporal lobe surgery: role of contralateral
      damage as revealed by 1H magnetic resonance spectroscopy and T2 relaxometry.
AB  - We assessed performance on selected tests of verbal memory in 48 patients who had
      undergone either anterior temporal lobectomy or selective amygdalo
      hippocampectomy for the relief of pharmacologically intractable epilepsy. We
      related performance both to the side of surgical excision and to the presence or
      absence of abnormalities in the contralateral, unoperated, temporal lobe, as
      revealed by proton magnetic resonance spectroscopy (1H MRS) or T2 relaxometry.
      There were abnormalities on the unoperated side detected by 1H MRS in 50% of the
      34 patients who successfully underwent spectroscopy, and by T2 relaxometry in 33%
      of the complete series of 48 patients. There was no systematic relationship
      between seizure outcome and the presence or absence of abnormalities on the
      unoperated side. Verbal memory deficits were present in patients with left-sided
      excision, regardless of whether there were abnormalities on the unoperated side.
      The patients with right-sided excision also had verbal memory deficits, but only
      in the group with magnetic resonance abnormalities on the contralateral (ie,
      left) side and only on delayed recall. The study extends previous findings on the
      role of the temporal lobes in memory and highlights the role of these new
      magnetic resonance techniques in relating cognitive processes to brain
      structures.

PMID- 7723974
TI  - Alien hand syndrome: interhemispheric motor disconnection due to a lesion in the
      midbody of the corpus callosum.
AB  - The neuroanatomic substrate of the alien hand syndrome has remained controversial
      due to the noncircumscribed nature of cerebral injuries present in most cases.
      There have been few cases studied in which damage was restricted to portions of
      the body of the callosum, and most of those involved surgical callosotomy for
      tumors or epilepsy. We report the case of a woman with a transient alien hand
      syndrome caused by a stroke limited to the middle and posterior portions of the
      body of the corpus callosum. This case provides supportive evidence for damage to
      the midbody of the corpus callosum as the anatomic basis of nondominant alien
      hand syndrome and conforms to a model of interhemispheric motor disconnection as
      the essential component of this unusual behavioral syndrome. This disconnection
      can occur with injuries involving interhemispheric premotor and motor fibers
      traveling in the midportion of the callosum in individuals with left hemisphere
      dominance for motor activities.

PMID- 7723975
TI  - Multiple sclerosis can cause visual processing deficits specific to texture
      defined form.
AB  - We performed the following tests in 25 patients with multiple sclerosis (MS) and
      25 age-matched control subjects: recognition of texture-defined (TD) letters;
      recognition of motion-defined (MD) letters; and recognition of luminance-defined
      (LD) letters of 96% and 11% contrasts. Six patients with normal visual acuity
      were abnormal on recognizing TD letters, of whom one gave normal results on all
      other tests. Eleven patients were abnormal on MD letter recognition, of whom four
      gave normal results on all other tests. Visual acuity for letters of 11% contrast
      were abnormally low in seven patients, of whom two gave normal results on all
      other tests. We conclude that the neural mechanisms underlying recognition of TD,
      MD, and low-contrast LD letters in subjects with normal visual acuity are
      sufficiently different that they can be differentially damaged by MS. Therefore,
      TD, MD, and LD letter tests provide complementary information. We suggest that
      the detection of TD letters can be disrupted by demyelination of long-range
      horizontal connections between orientation-tuned neurons in the striate cortex.

PMID- 7723976
TI  - Monoclonal antibodies preventing leukocyte activation reduce experimental
      neurologic injury and enhance efficacy of thrombolytic therapy.
AB  - We evaluated the ability of monoclonal antibodies directed against leukocyte
      adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], CD18) to enhance
      the efficacy of thrombolysis in a rabbit cerebral embolism stroke model. Both
      tissue-type plasminogen activator (tPA) and anti-CD18 (alpha-CD18) monoclonal
      antibody administered 5 minutes after embolization increased the quantity of
      clots required to produce neurologic damage, although the combination was no more
      effective than either substance alone. Neither alpha-CD18 nor anti-ICAM-1 (alpha
      ICAM-1) improved neurologic outcome at postischemic delays of 15 or 30 minutes.
      However, the combination of alpha-ICAM-1 (15 minutes after embolization) and tPA
      (2 hours after embolization) significantly improved neurologic outcome even
      though neither substance was effective alone at these postembolization delays.
      These findings suggest that prevention of leukocyte adhesion increases the
      postischemic duration at which thrombolytic therapy remains effective.

PMID- 7723977
TI  - Cheyne-Stokes respiration in ischemic stroke.
AB  - We monitored breathing pattern and arterial oxygen saturation in 32 conscious
      patients with acute ischemic stroke. Seventeen (53%) had Cheyne-Stokes
      respiration with concomitant drops in oxygen saturation, unrelated to infarct
      location. The ventilatory disturbance promptly reversed after intravenous
      theophylline ethylenediamine or oxygen inhalation. The therapy is a simple way of
      improving arterial oxygenation in a large subgroup of patients with acute
      ischemic stroke.

PMID- 7723978
TI  - Botulinum toxin treatment of essential head tremor.
AB  - We examined in a double-blind, placebo-controlled study the effects of botulinum
      toxin in 10 patients with essential head tremor. Each subject received two
      treatments approximately 3 months apart, one with botulinum toxin injections and
      another with normal saline injections into the sternocleidomastoid and splenius
      capitis muscles. The subjects were assessed before each treatment and at 2, 4,
      and 8 weeks after injections. There was moderate to marked improvement in
      clinical ratings in five subjects after botulinum toxin injections and in one
      subject after placebo. There was moderate to marked subjective improvement in
      five patients with botulinum toxin as compared with three subjects with placebo.
      Side effects were mild and transient. We conclude that botulinum toxin may be
      useful for patients with essential head tremor who have failed to benefit from
      oral medications.

PMID- 7723979
TI  - Plasmapheresis in fulminant acute disseminated encephalomyelitis.
AB  - We describe two patients with fulminant acute disseminated encephalomyelitis
      (ADEM) treated with plasmapheresis after they failed to improve on steroids. Both
      patients improved concomitant with the plasma exchange. These are the first
      reported cases of fulminant ADEM with extensive white matter abnormalities on
      imaging studies treated with a regimen of plasmapheresis and steroids.
      Plasmapheresis may be beneficial in this disorder.

PMID- 7723980
TI  - Autopsy-proven amyotrophic lateral sclerosis, Waldenstrom's macroglobulinemia,
      and antibodies to sulfated glucuronic acid paragloboside.
AB  - Antibodies to myelin-associated glycoprotein (MAG) are found in patients with
      both monoclonal gammopathy and sensorimotor peripheral neuropathy but almost
      never in patients with amyotrophic lateral sclerosis (ALS). Ninety percent of
      patients with anti-MAG activity also have antibodies to sulfated glucuronic acid
      paragloboside (SGPG). We studied a patient with autopsy-proven ALS who had high
      titers of anti-SGPG but normal anti-MAG--one more unexplained immunologic
      abnormality in ALS.

PMID- 7723981
TI  - Ginseng-associated cerebral arteritis.
AB  - We report a 28-year-old woman who had a severe headache after ingesting a large
      quantity of ethanol-extracted ginseng. Cerebral angiograms showed "beading"
      appearance in the anterior and posterior cerebral and superior cerebellar
      arteries, consistent with cerebral arteritis. The close temporal association
      between intake of ginseng and cerebral arteries suggests a causal relationship.

PMID- 7723982
TI  - Blink- and saccade-induced seesaw nystagmus.
AB  - A 29-year-old woman with bitemporal hemianopia persisting after a suprasellar
      germinoma was resected twelve years previously had brief periods of pendular
      seesaw nystagmus after blinks and horizontal or vertical saccades. Nystagmus may
      have been suppressed during fixation, and escaped only when fixation was
      interrupted by blinks or saccades.

PMID- 7723983
TI  - Hughlings Jackson's theory of recovery.
AB  - John Hughlings Jackson proposed a mechanism of neurologic compensation based on
      his theory of cerebral localization. According to Hughlings Jackson, there are
      three levels of evolution of the nervous system. Each element of each level
      contains a complete representation of the next lower level. Each element of the
      middle and highest levels contain a representation of the entire body, weighted
      for a particular part of the body. If the nervous system is damaged so that an
      area heavily weighted for a particular part of the body is destroyed, less
      heavily weighted areas are immediately activated according to their weighting.
      This activation partially compensates for the function of the destroyed tissue.
      As time passes, the weighting of representation in the unaffected areas changes,
      amplifying the degree of recovery. Recent clinical studies and PET cerebral blood
      flow studies show that various ipsilateral and contralateral areas are activated
      in recovery. The activated areas reside in what Hughlings Jackson would call the
      middle and highest evolutionary levels. Modern clinical and neurophysiologic
      observations are therefore consistent with Hughlings Jackson's theory of
      compensation.

PMID- 7723984
TI  - Status of clinical research in neurology. Report of the Clinical Research
      Subcommittee of the Scientific Issues Committee of the American Academy of
      Neurology.

PMID- 7723985
TI  - Reversible downbeat nystagmus and ataxia in felbamate intoxication.

PMID- 7723986
TI  - Acute, painful, pupil-involving third nerve palsy in chronic inflammatory
      demyelinating polyneuropathy.

PMID- 7723987
TI  - Secondarily generalized seizures.

PMID- 7723988
TI  - Secondarily generalized seizures.

PMID- 7723989
TI  - Nerve conduction studies in diabetic neuropathy.

PMID- 7723990
TI  - Interventional neurology.

PMID- 7723991
TI  - Interventional neurology.

PMID- 7723992
TI  - Interventional neurology.

PMID- 7723993
TI  - Lorazepam for status epilepticus.

PMID- 7723994
TI  - Operation tropic refuge: the East Wood rescue.
AB  - The U.S. Coast Guard rescued 525 Chinese nationals and ten Indonesian crewmen
      from the disabled motor vessel East Wood. They were participating in a human
      smuggling operation. Subjected to a trying ordeal at sea, these individuals were
      at great risk to life and health but survived remarkably well because of their
      good health, age, and mutual cooperation. The U.S. military organized the joint
      task force, Operation Provide Refuge, to provide humanitarian aid. The task force
      rapidly mobilized resources to support camp development on Kwajalein Island and
      provide nutrition and health care to the stranded travelers. Preventive Medicine
      personnel, called in at the beginning of the operation, helped develop a healthy
      campsite, which contributed to a relatively uneventful refugee experience. Close
      liaison with the local medical resources on Kwajalein was essential to the
      success of the operation.

PMID- 7723995
TI  - Patenting medical inventions.
AB  - Medical, dental, nursing, and biomedical personnel often perform critical
      research that can lead to patents. Similarly, patentable discoveries can be made
      during the normal course of medical practice, e.g., the development of new
      biocompatible polymers, improved dental materials, new or modified catheters, new
      laboratory diagnostic tests, and improved medical devices. Many inventions may
      not be patented in federal organizations due to the lack of information available
      on the patenting process. In this article, the financial benefits that can be
      derived from patenting inventions are discussed, as well as the different types
      of patents that can be obtained, the conditions for patentability, bars or
      restrictions to obtaining a patent, the importance of proper record keeping, and
      the steps to take toward getting an invention patented.

PMID- 7723996
TI  - Regulation of beta-lactamase induction in gram-negative bacteria: a key to
      understanding the resistance puzzle.
AB  - Infections caused by drug-resistant microorganisms have posed a medical challenge
      since the advent of antimicrobial therapy. With the emergence of resistant
      strains, new antibiotics were available and introduced with great success until
      this decade. The appearance of multiresistant microorganisms pose a real and
      immediate public health concern. Are we entering into the post-antibiotic era?
      Will we return to pre-antimicrobial-era conditions, with morbidity and mortality
      resulting from untreatable infectious complications? The race to stay ahead of
      multiresistance involves not only continued drug development and selective use
      but elucidation of bacterial regulation of resistance. One way to ensure
      continued success of antimicrobial therapy is the identification of new bacterial
      targets--genes and their products involved in regulating or mediating resistance.
      Discussion will focus on one well-defined resistance mechanism in Gram-negative
      bacteria, the chromosomally located amp operon, responsible for one mechanism of
      beta-lactam resistance.

PMID- 7723997
TI  - Fine needle aspiration of palpable breast masses with immediate cytologic
      interpretation in an OB/GYN residency training program: a preliminary report.
AB  - Increasing emphasis has been placed on the training of obstetrics and gynecology
      residents in the evaluation of patients with breast disease. In the past, one had
      to refer to the surgery, radiology, or pathology literature to obtain current
      information on fine needle aspiration. With the present mandate to include breast
      disease in the academic curricula of obstetrics and gynecology residency
      training, the Department of Obstetrics and Gynecology, Tripler Army Medical
      Center, initiated training in breast evaluation. This preliminary report
      describes the Tripler Obstetrics and Gynecology Department Breast Evaluation
      Clinic and presents the findings of the first 40 patients.

PMID- 7723998
TI  - Preventing post-traumatic stress disorder resulting from military operations.
AB  - Military personnel are at high risk for developing post-traumatic stress disorder
      (PTSD), historically 10 to 50% of all casualties. The best treatment is to
      provide an opportunity for rest and ventilation of feelings and then to return
      the person to duty and to his or her peer group. Preventing the cycle of PTSD
      from starting and thus decreasing psychiatric casualties is feasible. This can be
      done by promoting unit cohesion and morale, ensuring that individuals know their
      jobs, inducing stress during training so individuals will be better prepared to
      cope, providing realistic information about what to expect in combat, and holding
      group debriefings immediately after any traumatic event. This paper discusses
      various models for preventing PTSD and examines future directions for the
      prevention of PTSD.

PMID- 7723999
TI  - The inpatient experience of a U.S. Army combat support hospital in the Persian
      Gulf during non-combat and combat periods.
AB  - To identify the key factors that control the workload of a U.S. military hospital
      during deployment, we studied all 574 admissions to the 46th Combat Support
      Hospital (CSH) during its deployment during Operations Desert Shield and Desert
      Storm. Date of admission, admission diagnosis, admitting service, length of
      hospitalization, disposition, nationality, and sex for each admission were
      analyzed. The workload of the 46th CSH varied markedly during the different
      periods of its deployment. Three hundred seventy-eight (66%) of the 574
      admissions occurred during Operation Desert Shield, although admissions occurred
      at the greatest rate during the short Ground War phase of Operation Desert Storm.
      Iraqis accounted for 82% of the admissions during the Ground War and 51% of the
      total Desert Storm admissions. The most important factors determining the
      workload of the 46th CSH were the combat situation, effectiveness of the air
      evacuation system, and the obligation to treat enemy soldiers and civilians.

PMID- 7724000
TI  - The effect of the M43 and M17 protective masks on stereoacuity.
AB  - The purpose of this study was to evaluate the effects of the M17 and M43
      protective masks on stereoacuity. Twelve subjects were tested on the Keystone
      diagnostic series stereopsis test at nearpoint and the Howard-Dolman apparatus at
      40 cm and 6 m. Stereopsis was evaluated without a mask and with the M43 and M17
      masks. Stereoacuity was decreased at near point with both masks and was not
      significantly affected at the 6-m distance.

PMID- 7724001
TI  - Bouveret's syndrome: a rare consequence of malignant cholecystoduodenal fistula.
AB  - We report a case of duodenal gallstone obstruction, resulting from
      cholecystoduodenal fistula. Fistulization was associated with a repeat chronic
      inflammation and metastatic carcinomatous infiltration. The diagnosis was
      confirmed by ultrasonography, barium meal examination, and gastroscopy. An
      attempt at endoscopic extraction was unsuccessful and the patient was referred
      for operative therapy. We present a graphic algorithm for decision-making in
      Bouveret's syndrome.

PMID- 7724002
TI  - Kidney transplantation decreases the tissue level of advanced glycosylation end
      products.
AB  - We have studied the effect of chronic renal failure (CRF) and kidney
      transplantation on advanced glycosylation end-products (AGE) measured as collagen
      linked fluorescence (CLF) in the skin and peritoneum of non-diabetic patients. Of
      34 patients with CRF, 18 were studied before the commencement of peritoneal
      dialysis (CRF group), and 16 were studied 5-31 weeks after kidney transplantation
      (transplant group). The control group consisted of 24 patients with normal renal
      function. Skin CLF in the CRF group (20.9 +/- 2.02 U/mg) was higher than in the
      control (8.52 +/- 1.08 U/mg, P = 0.0001) and transplant groups (10.7 +/- 2.43
      U/mg, P = 0.003). Peritoneal CLF in the CRF group (30.5 +/- 5.64 U/mg) was higher
      than in the control group (16.1 +/- 2.25 U/mg, P = 0.031) but was not different
      from the transplant group (19.4 +/- 3.66 U/mg, P = 0.11). Peritoneal CLF of
      control and transplant groups were not different (P = 0.45). The results of this
      study suggest that restoration of renal function affects tissue AGE levels.

PMID- 7724003
TI  - Idiopathic membranous nephropathy in two siblings.

PMID- 7724004
TI  - Renal thrombotic microangiopathy in patients with chronic myelogenous leukaemia
      treated with interferon-alpha 2b.

PMID- 7724005
TI  - Fatal fungal peritonitis by Trichoderma longibrachiatum complicating peritoneal
      dialysis.

PMID- 7724006
TI  - Microalbuminuria in diabetes mellitus--is there a structural basis?

PMID- 7724007
TI  - Mannitol-induced acute renal failure.

PMID- 7724008
TI  - Matrix stones and acquired renal cysts in a non-dialysed patient with chronic
      renal failure.

PMID- 7724009
TI  - The spouse as a risk factor in central venous catheter care for haemodialysis.

PMID- 7724011
TI  - Glomerular involvement in type I monoclonal cryoglobulinaemia.

PMID- 7724010
TI  - Acute renal failure caused by primary splenic plasmacytoma.

PMID- 7724012
TI  - Photosensitivity, proteinuria and membranous nephropathy in a young woman.

PMID- 7724013
TI  - Problems with incomplete parathyroidectomy.

PMID- 7724014
TI  - Urea kinetic modelling.

PMID- 7724015
TI  - In-vitro studies of cytokine-inducing substance (CIS) transfer across
      haemodialysis membranes--a cautionary note.

PMID- 7724016
TI  - Lipids--what is the evidence for their role in progressive renal disease?

PMID- 7724017
TI  - Ondansetron for symptomatic relief in terminal uraemia.

PMID- 7724019
TI  - Fungal peritonitis complicating continuous ambulatory peritoneal dialysis: use of
      high dosages of fluconazole or solely removal of the catheter?

PMID- 7724018
TI  - Streptococcus pyogenes peritonitis associated with genital swelling and
      gastroenteritis caused by Cryptosporidium and Salmonella paratyphi B in an HIV
      infected patient on CAPD.

PMID- 7724020
TI  - Amelioration of cyclosporin nephrotoxicity by Cordyceps sinensis in kidney
      transplanted recipients.

PMID- 7724021
TI  - Low molecular weight heparin--does it favourably affect lipid levels?

PMID- 7724022
TI  - Should older patients receive renal transplants?

PMID- 7724023
TI  - Familial membranoproliferative glomerulonephritis.
AB  - Four and two male sibs of two separate families who had biopsy-proven
      membranoproliferative glomerulonephritis (MPGN) are presented. In the first
      family four sibs of the first-degree consanguineous marriage showed the clinical
      picture of nephrotic syndrome without hypocomplementaemia at initial laboratory
      findings. In the second family two affected sibs showed nephrotic and nephritic
      syndromes on admission. Family investigations showed normal serum complement,
      immunoglobulins, T-cell subsets, urine analysis, and serum biochemistry. HLA
      typing in the two families revealed a common antigen HLA A2 in all affected sibs.
      Some other reports give suggestive evidence of MPGN in siblings but this is the
      first report that showed the occurrence of MPGN in four sibs. Our data
      strengthened the concept that genetic factors are involved in the development of
      MPGN but additional immunogenetic studies will shed light on the genetic aspects
      of the disease.

PMID- 7724024
TI  - Low-dose angiotensin-converting-enzyme inhibitor captopril to reduce proteinuria
      in adult idiopathic membranous nephropathy: a prospective study of long-term
      treatment.
AB  - The objective of this trial was to determine the long-term antiproteinuric effect
      of a low-dose of the angiotensin-converting-enzyme inhibitor (ACEI) captopril in
      patients with idiopathic membranous nephropathy (IMN), stable renal function, and
      no indicators of poor long-term prognosis. Fourteen adult IMN outpatients (median
      age 53 years) with a median duration of disease of 3 years received 12.5 mg of
      captopril twice a day for 12 months in a prospective trial. The effects of
      therapy were evaluated on the basis of plasma creatinine, 24-h proteinuria, the
      proteinuria selectivity index, albuminaemia, and serum IgG levels. Data were
      compared by means of the non-parametric paired Wilcoxon test. Three patients
      withdrew from the trial. Renal function remained stable in the 11 who completed
      the study. A clear decrease in proteinuria was observed after 1 month of therapy,
      which persisted with time and was associated with a trend towards a further long
      term decrease. An increase in serum albumin was only observed after 6 months of
      therapy, again with a trend towards an increase over time. Serum IgG levels
      increased during therapy. This study together with data from the literature
      suggests a potential long-term benefit of angiotensin-converting-enzyme
      inhibitors in moderately proteinuric IMN. Prospective trials comparing low-dose
      and high-dose ACEI to no treatment or a placebo in non-severe IMN are now
      required.

PMID- 7724025
TI  - Cerebral venous sinus thrombosis in minimal change nephrotic syndrome.
AB  - Three cases of cerebral venous sinus thrombosis (CVST) occurring in patients with
      minimal change nephrotic syndrome (MCNS) are described. Personality change in two
      of these patients was wrongly attributed to steroid therapy prior to the
      discovery of the CVST. In addition, von Willebrand factor (vWF) levels were
      grossly elevated in one patient, during a previous relapse of MCNS, prior to
      developing CVST, and may be a useful prognostic tool in predicting thrombotic
      events in nephrotic patients.

PMID- 7724026
TI  - HIV-associated IgA nephropathy--a post-mortem study.
AB  - Between November 1983 and December 1991, we undertook a systematic study of
      kidney in deceased AIDS patients using light and immunofluorescence microscopy.
      Among the 116 examined kidneys (from 106 men and 10 women), nine (7.75%) showed
      diffuse mesangial IgA deposits. By light microscopy, glomerular lesions were
      absent or moderate (mesangial hypertrophy or some mesangial deposits). Urinary
      abnormalities were mild in all cases. Our study shows that the association
      between IgA nephropathy and HIV infection is not rare, and a review of the
      literature disclosed 18 reported cases. Some reported immunopathogenic data
      support the possibility of a link between HIV infection and IgA nephropathy.

PMID- 7724028
TI  - Constant infusion clearance is an inappropriate method for accurate assessment of
      an impaired glomerular filtration rate.
AB  - Recently renewed interest has been focused on constant infusion clearance to
      assess GFR accurately. In this study we compared GFR and ERPF calculated from the
      constant infusion method (CIM = I x V/P) with that calculated from the standard
      method (StM = U x V/P), in 100 patients with renal disease who were subdivided in
      four groups according to their GFR-StM (< 30; 30-60; 60-90; > 90 ml/min). After a
      priming dose, a constant infusion of 125I-iothalamate (= GFR) and 131I-hippurate
      (= ERPF) was started at 9 a.m. The infusion rates were individually adjusted to
      the GFR which was approximated from the serum creatinine concentration. After a
      90-min equilibration period, GFR-StM and ERPF-StM were determined for two 2-h
      periods. These values were compared with GFR-CIM and ERPF-CIM calculated from the
      plasma concentration of the respective tracers at the end of each 2-h period (=
      210 and 330 min). In the patient group with GFR-StM < 30 ml/min, the 125I
      iothalamate plasma concentration increased progressively over time. Consequently,
      average GFR-CIM at 210 min (34.2, SE +/- 2.1 ml/min) was higher than the GFR-CIM
      at 330 min (31.9, SE +/- 2.0 ml/min; P < 0.001). In addition both values were
      significantly higher than the corresponding GFR-StM values (18.1 +/- 2.4 and 15.3
      +/- 1.6 ml/min respectively). In the two patient groups with GFR-StM > 60 ml/min,
      the 125I-iothalamate plasma concentration decreased progressively over
      time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724027
TI  - Light-chain-induced renal tubular acidosis: effect of sodium bicarbonate on
      sodium-proton exchange.
AB  - We measured sodium-proton (Na+/H+) exchange in lymphocytes and platelets of a 46
      year-old woman with the adult Fanconi syndrome before, during, and after
      treatment with NaHCO3. Kappa light chains in her urine and unique but rarely
      observed crystalline structures confirmed the presence of light-chain
      nephropathy. Her glomerular filtration rate was only moderately impaired at 72
      ml/min. NaHCO3 at 1, 3, and 5 mmol/kg/day for 5 days increased her serum HCO3 and
      pH from 17 to 21 mmol/l and 7.28 to 7.39 respectively. Plasma renin and
      aldosterone values were decreased by NaHCO3. Na+/H+ exchange (delta Hi/min) was
      measured with the fluorescent marker BCECF after acidification of lymphocytes and
      platelets with sodium propionate at five (10-50 mM) doses. Na+/H+ exchange was
      accelerated in this patient compared to normal controls. NaHCO3 treatment
      significantly decreased Na+/H+ exchange in lymphocytes, but not in platelets.
      These findings suggest that Na+/H+ exchange can be influenced by NaHCO3 ingestion
      at doses that only modestly affect systemic pH. Since Na+/H+ exchange is involved
      in stimulus response coupling, cell growth regulation, cell differentiation, and
      perhaps the progression of nephrosclerosis, these observations may have clinical
      relevance.

PMID- 7724029
TI  - Diagnostic value of serum peptides of collagen synthesis and degradation in
      dialysis renal osteodystrophy.
AB  - The assay of serum peptides of bone collagen formation and degradation could
      potentially provide an indirect estimate of the rate of bone turnover. In our
      study we have measured serum levels of the carboxy-terminal propeptide of type I
      procollagen (PICP) as a marker of bone formation and serum levels of the
      pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a
      marker of bone resorption in 53 patients (47.7 +/- 10 years, M +/- SD) on
      haemodialysis (for 9.5 +/- 3.8 years) and affected by renal osteodystrophy.
      Besides PICP and ICTP, patients were also sampled for serum intact and C-terminal
      PTH, osteocalcin (BGP) and alkaline phosphatase (AP). A transiliac bone biopsy
      for histomorphometry was also performed in all. As expected both PTH assays, BGP
      and AP, were correlated reciprocally and to histomorphometric parameters. As for
      serum levels of PICP, they were on average increased (268.5 +/- 104.9 ng/ml, M +/
      SD) compared to normals (range 66-176), but not correlated to classical humoral
      markers of hyperparathyroidism (PTH and AP), with the exception of BGP (with a
      rather low r value: 0.365, P < 0.01), nor to histomorphometric indices of bone
      resorption and formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724030
TI  - Ultradian variation in serum phosphate concentration in patients on
      haemodialysis.
AB  - To study how much the serum phosphate concentration could vary on the day before
      scheduled dialysis we obtained 24-37 timed measurements during 24 h in nine
      patients on maintenance haemodialysis. During the observation there was an
      increase in serum phosphate concentration of 0.239 +/- 0.022, P < 0.01).
      Surprisingly six of the nine patients exhibited nine statistically and clinically
      significant nadirs with decrements of 0.21 +/- 0.04 mmol/l against an intra-assay
      standard deviation of about 0.05 mmol/l. Five of the nadirs occurred at 11.40
      14.50, mean 12.59, and three at 19.00-21.30, mean 20.00. We found no coinciding
      changes in the serum calcium concentration. These findings indicate that serum
      phosphate concentrations do not always reflect phosphorus balance or intake.

PMID- 7724031
TI  - Cancer antigen 125: a bulk marker for the mesothelial mass in stable peritoneal
      dialysis patients.
AB  - Mesothelial cells that line the peritoneal cavity are capable of producing
      several proinflammatory cytokines such as interleukin-6 and interleukin-8. Since
      they are the most numerous cell in the peritoneal cavity when the lining
      mesothelial cells are included, they may play a major role in the local
      antibacterial defence mechanism. Cancer antigen (CA)125 is expressed by
      mesothelial cells (as by other coelomic epithelium-derived cells) and might
      therefore be considered a marker of the mesothelium. The aim of this study was to
      determine whether CA125 is a bulk or an activation stage mesothelial cell marker.
      A positive correlation was found between the mesothelial cell number and the
      CA125 concentration in dialysate of stable PD patients (P = 0.03). CA125 release
      by mesothelial cell cultures during confluence showed that the release per cell
      was constant in time. Stimulation of mesothelial cells in a confluential phase
      with IL1 beta, TNF alpha, IFN gamma and TGF beta did not result in an increase in
      CA125 release. Cell lysis showed that CA125 is also present intracellularly. This
      implies that release of intracellular CA125 can be a disturbing factor in
      interpreting the CA125 concentration of dialysate in situations where mesothelial
      cell death may occur, such as in peritonitis. It can be concluded, that our data
      show that dialysate CA125 is a bulk marker for the mesothelial cell mass in
      stable PD patients and can thus provide data on the state of the peritoneal
      membrane in the follow-up of the individual patient.

PMID- 7724032
TI  - On genetic heterogeneity, anticipation, and imprinting in polycystic kidney
      diseases.

PMID- 7724033
TI  - Effect of calcitriol replacement on serum calcitonin and parathyroid hormone
      levels in CAPD patients.
AB  - Calcitonin-secreting cells, 'C cells', have specific receptors for calcitriol,
      thus the calcitriol deficiency in uraemia may affect calcitonin secretion and/or
      production. The aim of the present study was to evaluate in CAPD patients the
      effect of calcitriol replacement (4 weeks of oral calcitriol, 0.5 micrograms/day)
      on both, basal calcitonin concentration and calcitonin response to calcium
      infusion (calcium gluconate, 3 mg/kg/h). Calcitriol replacement produced a
      normalization of serum calcitriol level without a significant change in serum
      calcium concentration. After calcitriol replacement, basal calcitonin increased
      from 78 +/- 15 to 101 +/- 13 pg/ml, P < 0.05. The increment in calcitonin induced
      by a calcium infusion was lower after (15 +/- 4 pg/ml) than before (29 +/- 4
      pg/ml) calcitriol replacement. In addition, calcitriol administration induced a
      decrease in serum PTH level. Replacement of calcitriol in CAPD patients produced
      an increase in serum calcitonin concentration and a decrease in the calcitonin
      response to hypercalcaemia.

PMID- 7724034
TI  - Protein loss and genetic polymorphism of apolipoprotein(a) modulate serum
      lipoprotein(a) in CAPD patients.
AB  - Lipoprotein(a) (Lp(a)) serum concentrations and apoprotein(a) isoforms were
      measured in 64 uraemic patients treated with continuous ambulatory peritoneal
      dialysis (CAPD) and compared with those in 155 normal controls. The mean Lp(a)
      values were 44 +/- 5 mg/dl (median 30 mg/dl) in CAPD patients and 22 +/- 3 mg/dl
      (9 mg/dl) in controls (P < 0.01). Within the most common apo(a) isoform classes,
      higher concentrations of Lp(a) were seen in the CAPD patients compared with the
      controls (P < 0.05). These results were not influenced by differences in the
      frequency distribution of the apo(a) isoforms. Twenty-six CAPD patients (41%)
      were suffering from coronary artery disease and 63% of these patients exhibited
      low-molecular-weight isoforms < or = S2, compared with 31% of the patients
      without coronary artery disease. Furthermore a positive correlation between the
      daily protein (r = 0.4, P = 0.02) and albumin loss (r = 0.39, P = 0.2) into the
      dialysis fluid and the Lp(a) serum concentration was also observed. Therefore we
      suggest that the elevated Lp(a) concentrations in CAPD patients are influenced by
      the amount of protein loss into the dialysate and by the allelic variation of the
      apo(a) isoform. In addition to the typical dyslipidaemia found in CAPD patients,
      high levels of Lp(a) and specific isoform patterns may in turn contribute to the
      elevated risk of coronary artery disease and other cardiovascular complications.

PMID- 7724035
TI  - Is dietary intervention effective in post-transplant hyperlipidaemia?
AB  - Current therapies for hyperlipidaemia following renal transplantation include
      modification of dietary fat. We examined the effect of dietary intervention
      according to the American Heart Association Step One diet on serum lipids and
      lipoproteins among 26 men and women with post-transplant hyperlipidaemia. Weighed
      dietary records showed that the intake of total fat decreased from 30 to 27% and
      the intake of saturated fat decreased from 12 to 8% of total calories. Body
      weight remained stable throughout the study. Serum total, LDL and HDL cholesterol
      levels were unchanged following 12 weeks of therapy. Serum triglyceride levels
      decreased slightly. The decrease was seen only in participants with a body mass
      index < 26 kg/m2, compared to those whose body mass index was > or = 26 kg/m2
      (0.4 versus 0 mmol/l; P = 0.03). Serum LDL cholesterol and triglyceride levels
      were significantly correlated with serum creatinine levels. In conclusion, among
      renal transplant recipients, hyperlipidaemia appears to be partly related to
      impairment of renal function, and may not be responsive to modification of
      dietary fat without weight reduction attempted on an outpatient basis.

PMID- 7724036
TI  - Physical performance does not improve in elderly patients following successful
      kidney transplantation.
AB  - In a prospective study before, and during 1 year following, kidney
      transplantation, physical strength and performance were tested in patients over
      the age of 60 and in younger control patients. Quadriceps strength increased
      significantly in the control patients (+3.3 +/- 3.2 kg, n = 11, P = 0.007) but
      remained stable in the successfully grafted elderly patients (-0.1 +/- 4.2 kg, n
      = 16). Grip strength tended to increase in the control patients (P = 0.064) but
      not in the elderly. Stepping up on a chair--a test of strength and coordination
      in combination--could be performed by all control patients on all occasions.
      Fourteen of 16 elderly patients managed it before transplant, but only 3/12 after
      3 weeks, 5/13 after 6 months, and 10/16 after 1 year. Forced expiratory volume
      during 1 s and working capacity on the ergometer bicycle also tended to decline
      during 1 year. We conclude that the average elderly person does not gain strength
      during 1 year after successful kidney transplantation.

PMID- 7724037
TI  - Hypertension-induced renal injury: is mechanically mediated interstitial
      inflammation involved?

PMID- 7724038
TI  - Outcome of renal transplantation in patients over the age of 60: a case-control
      study.
AB  - The outcome of kidney transplantation in 70 consecutive patients aged 60 years or
      more was compared to that of matched contemporary controls aged 18-54 years.
      Although the elderly patients were a positive selection from a much larger
      population in dialysis their first-year mortality was significantly increased (8
      versus one of the controls, P = 0.016). Morbidity in bronchopneumonia was also
      increased (11 versus 2, P = 0.009). In the group of elderly patients six grafts
      were lost due to the death of the patient. Neither the rate of irreversible
      rejection nor the need for extra antirejection therapy differed between the
      groups. The increased mortality and morbidity suggest that the selection had not
      been too restricted. Thus kidney transplantation should only be offered to a
      minority of elderly uraemic patients.

PMID- 7724039
TI  - Renal allograft histology and correlation with function in children on triple
      therapy.
AB  - Histopathological findings of 13 LRD and 17 CAD renal allografts of paediatric
      recipients were prospectively semiquantitatively scored and correlated with
      clinical and functional parameters 18 and 36 months after transplantation. The
      most common findings at 18 months were diffuse interstitial fibrosis (incidence
      57%), glomerular mesangial matrix increase (91%), arteriolar intimal
      proliferation (70%), and tubular atrophy (83%). Most changes were mild and most
      biopsies were scored normal or borderline (Banff classification). At 18 and at 36
      months 30% of grafts showed mild chronic rejection (CR). Only two grafts showed
      grade II CR at 18 months and one graft grade III CR at 36 months. Progressive CR
      was not seen. Donor source or recipient age had no effect on graft histology.
      Vascular-interstitial cyclosporin (CsA) nephrotoxicity was not found. On the
      contrary, cumulative CsA dose (mg/kg/day) showed an inverse correlation with
      arteriolar intimal proliferation (P < 0.001). 51Cr-EDTA and lithium clearances
      showed inverse correlations with diffuse interstitial fibrosis and lymphocytosis.
      PAH clearance did not correlate with interstitial or vascular changes. The
      results indicate good prognosis in children on triple immunosuppression (with CsA
      administered in three doses/day to pre school children) regardless of donor
      source.

PMID- 7724040
TI  - Calcium-dependent conductances control neurones involved in termination of
      inspiration in cats.
AB  - Intracellular injection of the calcium chelator BAPTA into postinspiratory (PI)
      and late inspiratory neurones (late-I) of the ventral respiratory group of
      anaesthetised cat was performed to study the role of intracellular free calcium
      in patterning the activity of neurones controlling termination of inspiration.
      BAPTA injection into neurones resulted in an increase of input resistance and
      prolongation of action potential discharge with reduced adaptation. In addition,
      late-I neurones developed a secondary burst of action potentials during the
      postinspiratory phase of the cycle. We conclude that intracellular free calcium
      controls (1) the duration of activation and the degree of adaptation of PI
      neurones and (2) repolarisation of late-I neurones during postinspiration.

PMID- 7724041
TI  - Responses of retinal and tectal neurons in non-paralyzed toads Bufo bufo and B.
      marinus to the real size versus angular size of objects moved at variable
      distance.
AB  - Toads judge the real size of moving visual objects during prey-catching. But
      neither ganglion cells of the retinotectal projection nor tectal neurons showed a
      comparable phenomenon in muscle paralyzed toads. In non-paralyzed toads, however,
      tectal neurons, unlike neurons, displayed a sensitivity to the real size of an
      object moving at variable distance to the animal. Interestingly, this property
      was obtained both in monocular T5 smallfield neurons and in most of the
      investigated T4 widefield neurons.

PMID- 7724042
TI  - Melatonin inhibits luteinizing hormone releasing hormone (LHRH) induction of LH
      release from fetal rat pituitary cells.
AB  - The in vitro effect of melatonin on the release of luteinizing hormone (LH) and
      follicle stimulating hormone (FSH) from fetal rat pituitary cells was
      investigated. A significant inhibition of LH release induced by 10(-9) M
      luteinizing hormone releasing hormone (LHRH) was seen when cells were incubated
      with 10(-9) M melatonin. FSH release was unaffected by either LHRH alone or LHRH
      in combination with melatonin. In addition, the significant inhibitory effect of
      melatonin was reduced by pretreatment of the pituitary cells with 10(-10) M
      melatonin. These findings indicate that melatonin can act directly on the fetal
      pituitary gland to suppress LHRH-induced release of LH perhaps by a mechanism
      which eventually involves down-regulation of the melatonin receptors.

PMID- 7724043
TI  - Sulfated glycosaminoglycans and dyes attenuate the neurotoxic effects of beta
      amyloid in rat PC12 cells.
AB  - Glycosaminoglycan (GAG)-containing proteoglycans are associated with the neuritic
      plaques and cerebrovascular beta-amyloid deposits of Alzheimer's disease as well
      as with the amyloid deposits of prion and other disorders. GAGs and other sulfate
      containing compounds have previously been shown to bind beta-amyloid peptide in
      vitro, suggesting possible effects of beta-amyloid deposition and/or toxicity in
      vivo. Using reduction of the redox dye 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) to measure beta-amyloid neurotoxicity in rat
      pheochromocytoma PC12 cells, several polysulfated GAGs and synthetic sulfate
      containing compounds were found to attenuate the neurotoxic effects of beta
      amyloid fragments beta 25-35 and beta 1-40. These results suggest that by binding
      beta-amyloid these compounds may prevent toxic interactions of the peptide with
      cells.

PMID- 7724044
TI  - The ras-like rab3A protein is present in pinealocytes of the gerbil pineal gland.
AB  - As part of our molecular and functional characterization of the compartment of
      synaptic-like microvesicles (SLMVs) in mammalian pinealocytes, we have now
      analyzed the pineal gland of the Mongolian gerbil for the presence of rab3
      proteins. Members of this subfamily of small G proteins are thought to regulate
      the intracellular trafficking and/or membrane fusion of secretory vesicles.
      Immunostaining of serial semi-thin sections of plastic-embedded pineals with
      monoclonal antibodies which recognize rab3A revealed the occurrence of rab3A in
      pinealocytes throughout the gland. Rab3A immunoreactivity was markedly enriched
      in dilated pinealocyte process terminals known to contain accumulations of SLMVs.
      The latter could be labeled with the rab3 antibodies at the ultrastructural level
      when immunogold staining was performed. Our results lend further support to the
      hypothesis that mammalian pinealocytes are endowed with a population of SLMVs
      that serve secretory functions.

PMID- 7724045
TI  - Protein kinase C mediates neurotensin inhibition of inwardly rectifying potassium
      currents in rat substantia nigra dopaminergic neurons.
AB  - Whole-cell voltage-clamp recordings were used to investigate the molecular
      transduction mechanism by which neurotensin decreases the inwardly rectifying
      potassium conductance of dopaminergic (DA) neurons acutely isolated from the rat
      substantia nigra (SN). With sodium-free external solution, neurotensin evoked
      inward currents by reducing the inwardly rectifying K+ conductance. Neurotensin
      inhibition of the K+ current was blocked by the internal perfusion of 1 mM GDP
      beta-S. When DA neurons were internally perfused with 0.5 mM GTP-gamma-S, the
      reduction of K+ conductance produced by neurotensin became irreversible.
      Neurotensin still inhibited K+ currents in DA neurons pretreated with 500 ng/ml
      pertussis toxin (PTX). Dialyzing DA neurons with protein kinase C (PKC)
      inhibitors, staurosporine and PKC(19-31), prevented neurotensin from decreasing
      the potassium conductance. Our results propose that neurotensin activates PKC of
      SN DA neurons via PTX-insensitive G-proteins and that PKC mediates the
      neurotensin inhibition of inwardly rectifying potassium currents.

PMID- 7724046
TI  - Inhibition of brain macrophage/microglial respiratory chain enzyme activity in
      experimental autoimmune encephalomyelitis of the Lewis rat.
AB  - We measured the activities of five respiratory chain enzymes in brain
      macrophages/microglial cells from Lewis rats with experimental autoimmune
      encephalomyelitis (EAE) and found a significant reduction of the activity of
      nicotinamide adenine dinucleotide-dehydrogenase (NADH-DH), succinate cytochrome c
      reductase (SCCR) and succinate dehydrogenase (SDH) when compared with age-matched
      healthy control animals. The inhibition of NADH-DH (complex I) was specific for
      EAE, while we also found a reduction of SCCR and SDH activities (complex II) in
      newborn rats and adjuvant-immunised rats. Activities of NADH cytochrome c
      reductase (NCCR) and cytochrome c oxidase (COX) were not significantly changed.
      These observations demonstrate an impairment of brain macrophage/microglial
      respiratory chain function in central nervous system inflammation.

PMID- 7724047
TI  - Age-dependent increases of immunoreactive imidazoline receptors in the human
      brain: possible association of a 29/30 kDa protein with the I2-imidazoline
      receptor identified by [3H]idazoxan.
AB  - In the postmortem human brain (15 specimens of frontal cortex), the
      immunodetection and quantification of imidazoline receptor (IR) proteins (29/30
      and 47 kDa) and the specific binding of [3H]idazoxan to I2-IR were determined in
      parallel to study the effect of aging (range 3-89 years) on these proteins and
      its possible association. The immunoreactivity of the 29/30 kDa IR protein,
      similar to the I2-IR, showed a significant positive correlation with the age of
      the subjects at death (r = 0.54; P = 0.04). Moreover, the levels of this IR
      protein also correlated significantly with the density of I2-IR in the brain of
      the same subjects (r = 0.67; P = 0.01). It is suggested that the I2-IR labeled by
      [3H]idazoxan in the human brain is related to the 29/30 kDa IR protein identified
      by immunoblot analysis.

PMID- 7724048
TI  - Synaptosomal transport of branched chain amino acids in young, adult and aged rat
      brain cortex.
AB  - Uptake of branched chain amino acids (BCAA, leucine and isoleucine) was studied
      in synaptosomes prepared from the cerebral cortex of rats of 1, 3 and 24 months
      of age. In addition to the conventional low affinity sodium independent transport
      system, a high affinity sodium dependent stereospecific transport system for the
      transport of BCAA was identified in synaptosomes prepared from the cerebral
      cortex of the above three age groups. There was an overall decrease in Km and
      Vmax of both high and low affinity transport systems for leucine and isoleucine
      in the cortical synaptosomes of 24-month-old rats when compared with younger age
      groups. This study indicates that the non-neurotransmitter essential amino acids
      are transported by high and low affinity transport systems and these systems
      undergo age-dependent alterations. These changes might be due to the altered
      synthesis of these transporter proteins and/or synthesis of transporters with
      altered conformation and/or changes in the physical properties (fluidity) of the
      membrane. The decrease in the transport of BCAA is on a par with the decrease in
      the overall metabolism of BCAA in brain. As food consumption decreases in the
      older age groups of animals, the availability of essential amino acids to the
      tissues might also be lowered. Under such conditions, it is suggested that the
      observed increase in the affinity (decreased Km) of the carrier might be helpful
      in the supply of essential amino acids.

PMID- 7724049
TI  - Degeneration of the intrahippocampal routes of the perforant and alvear pathways
      in senile dementia of Alzheimer type.
AB  - In five autopsied brains with senile dementia of Alzheimer type, the
      intrahippocampal routes of the perforant and alvear pathways were demonstrated by
      assessment of the distribution of isomorphic gliosis. Our results suggest that
      the perforant pathway goes along the stratum lacunosum-moleculare of the
      hippocampus proper to end in the dentate gyrus after perforating the prosubiculum
      but does not traverse the hippocampal sulcus, and that the alvear pathway enters
      into the stratum oriens of the hippocampus proper and the alveus from the white
      matter ventral to the subiculum.

PMID- 7724050
TI  - Stria terminalis conveys a facilitatory estrogen effect on female rat lordosis
      reflex.
AB  - The effects of bilateral cut of the stria terminalis (ST) on the dosage of
      estradiol benzoate (EB) needed to induce the lordosis reflex in the
      ovariectomized female rat were examined. Seven different doses ranging 0.5-20
      micrograms were given s.c. in oil, daily for 2 days in a counterbalanced order,
      at 3-week intervals. The log dose-response relationship was linear in both ST-cut
      and sham-operated control rats. A significantly larger dose of 9.3 +/- 1.4 (mean
      +/- SEM) micrograms/day of EB was needed in the ST-cut rats (n = 8) to obtain a
      50% lordosis quotient than in the controls (n = 7), in which a 2.0 +/- 0.3
      micrograms/day dose had a similar effect. The slope of the dose-effect curve was
      significantly steeper in the ST-cut rats than in the controls. The ST mediates
      facilitatory effects of estrogen on the lordosis reflex that originate presumably
      in the amygdala.

PMID- 7724051
TI  - Decreased binding of growth hormone in the rat hypothalamus and choroid plexus
      following morphine treatment.
AB  - Male Sprague-Dawley rats were continuously infused with morphine through
      subcutaneously implanted mini-osmotic pumps over a period of 5 days. The binding
      of rat growth hormone (rGH) to specific sites in choroid plexus, cortex,
      hypothalamus, hippocampus and striatum was determined. It was found that in the
      acute phase of morphine administration the density of growth hormone-binding
      sites was significantly decreased in choroid plexus and in hypothalamus, but not
      in any other of the tissues studied. When tolerance to morphine was developed,
      the level of growth hormone-binding was restored to control level. In the acute
      phase, the plasma levels of GH, as measured by radioimmunoassay, correlated
      negatively with the density of the binding sites in choroid plexus and
      hypothalamus. The decrease in growth hormone-binding in these regions of the rat
      brain was also confirmed by SDS-polyacrylamide gel electrophoresis of cross
      linked complexes of the binding entities to 125I-labelled rGH as visualized by
      autoradiography. In experiments, where morphine was administrated by intermittent
      injections, a similar decrease in rGH-binding was observed. However, the time
      course of this decrease seemed to be dependent upon the route of administration.
      Following intracerebroventricular (i.c.v.) injections, the binding of the hormone
      was already affected after 30 min, whereas the binding of rGH in brain areas
      after subcutaneous (s.c.) injections was affected at a later stage.

PMID- 7724052
TI  - Hypothalamic distribution of astrocytes is gender-related in Mongolian gerbils.
AB  - Hypothalamic neuroglial ontogeny was examined during neonatal development of two
      hormone-sensitive, sex-specific nuclei, the pars compacta of the sexually
      dimorphic area (SDApc) and the suprachiasmatic nucleus (SCN) in the gerbil.
      Specific antibodies against vimentin and glial fibrillary acidic proteins (GFAP)
      identified neuroglia. Unbiased measures of labelled cell anatomical parameters
      were taken using stereomorphometric techniques. High numbers of cells in the
      female and male SCN immunoreacted with vimentin in neonates and GFAP in adults.
      Astrocytes containing vimentin or GFAP were few in number in the SDApc and
      surrounding areas in neonates and adults, respectively. There was a sex
      difference in the numerical density of both vimentin and GFAP-positive cells in
      the SCN. We suggest that (a) pre-astroglia are involved in gender-related
      organization of the SCN but not in SDApc, and (b) neuroglia have a sex-related,
      functional role in the mature SCN.

PMID- 7724053
TI  - Amyloid precursor protein mutation at codon 713 (Ala-->Val) does not cause
      schizophrenia: non-pathogenic variant found at codon 705 (silent).
AB  - In some families with early-onset Alzheimer's disease (AD) pathogenic mutations
      have been found in exons 16 and 17 of the amyloid precursor protein (APP) gene.
      One case of schizophrenia has been described with a mutation at codon 713. We
      have developed a single strand conformation polymorphism (SSCP) method that
      detects mutations in these exons and investigated 98 AD cases and 56 elderly
      healthy controls. An earlier reported mutation at codon 713 in a healthy control
      and a previously undescribed polymorphism at codon 705 in a sporadic case of AD
      were found. These mutations are probably not related to disease pathogenesis.

PMID- 7724054
TI  - Clonidine hypotension in spontaneously hypertensive rats (SHR) depends on the
      functional state of GABAergic and glutamatergic systems.
AB  - The effect of gamma-aminobutyric acid (GABA)A receptors and of the N-methyl-D
      aspartate (NMDA) subtype of glutamate receptor blockade on clonidine hypotension
      was studied. The experiments were performed on spontaneously hypertensive (SHR)
      and normotensive Wistar-Kyoto (WKY) rats. We found that the blockade of GABAA
      receptors line significantly (P < 0.01) reduced hypotensive responses to
      clonidine. Similarly, the NMDA receptor antagonist dizocilpine (MK-801)
      completely abolished the blood pressure lowering effect of clonidine. Our
      findings support the conclusion that clonidine hypotension is closely related to
      the functional state of both inhibitory GABAergic and excitatory glutamatergic
      systems.

PMID- 7724056
TI  - Toward tougher oversight of managed care: MSNJ proposals.
AB  - The Medical Society of New Jersey has developed a detailed position statement on
      the regulation of health maintenance organizations (HMO). This statement has been
      presented to an advisory committee of the New Jersey State Department of Health,
      which is preparing new HMO regulations.

PMID- 7724055
TI  - Adenosine analogs inhibit acetylcholine release and cyclic AMP synthesis in the
      guinea-pig superior cervical ganglion.
AB  - The ability of adenosine agonists to modulate the electrically evoked release of
      acetylcholine (ACh) from [3H]choline preloaded guinea-pig superior cervical
      ganglia (SCG) was investigated. The adenosine A1-receptor selective agonist N6
      cyclohexyladenosine (CHA) and 2-chloroadenosine (2-CADO) inhibited the evoked
      transmitter release, the effect being reversed by the A1-receptor selective
      antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and by sulmazole (SUL),
      which blocks both the A1-receptor and the adenylate cyclase inhibitory regulator
      Gi. In whole ganglia, CHA decreased both the basal and the forskolin (FSK)
      stimulated cyclic AMP synthesis. The latter effect was again prevented by the A1
      antagonist DPCPX. These results are compatible with the existence, in the guinea
      pig SCG, of adenosine A1-receptors, part of which are located on the presynaptic
      nerve terminals mediating an inhibition of ACh release.

PMID- 7724057
TI  - Nutritional implications of significant small bowel resection.
AB  - Nutrition support of the patient with short bowel syndrome is determined by the
      extent and location of bowel resection, the functional status of residual bowel,
      and presence or absence of the ileocecal valve. The authors discuss the
      consequences and treatments for bowel resection.

PMID- 7724058
TI  - Managing the triage of GI hemorrhage as a function of stability.
AB  - The authors present a refined triage tool to assist in the identification of
      patients with GI hemorrhage. Criteria include orthostasis; current, active GI
      hemorrhage; hemoglobin under 10 g/dl or a 3 g/dl drop from a known baseline; and
      history of underlying organ system dysfunction.

PMID- 7724059
TI  - Case report: fatal Pseudomonas aeruginosa pneumonia and sepsis.
AB  - The authors report a case of overwhelming Pseudomonas pneumonia with sepsis and
      death in a 54-year-old male; death resulted from jacuzzi exposure in an
      immunocompetent host. The patient died 24 hours after hospital admission from
      gram negative sepsis shock.

PMID- 7724060
TI  - Case report: intraspinal synovial cyst containing gas.
AB  - With MRI, an intraspinal synovial cyst appears as a hypointense, rounded,
      intraspinal lesion bearing similar signal characteristics to cerebrospinal fluid
      containing a signal void within it; this can be confused with calcium or
      hemosiderin within the cyst. In such cases, CT imaging can lead to a diagnosis.

PMID- 7724061
TI  - Towards the elucidation of the structural-functional relationship of inward
      rectifying K+ channel family.
AB  - With recent cDNA cloning of members of the inward rectifying K+ channel family,
      it was revealed that they have only 2 putative transmembrane regions with no
      voltage-sensor element. Based on the deduced primary structure, possible
      schematic models to explain their characteristic features are proposed in this
      article. The features are (1) blocking by intracellular Mg2+, (2) intrinsic
      gating, (3) the triple barrel structure of the inward rectifier K+ channel and
      (4) the activation by the direct interaction with G-protein subunits of the
      muscarinic K+ channel. The recent findings of the mutagenesis study of voltage
      gated K+ channels, which provide a clue for the structural-functional study of
      the inward rectifying K+ channels, are also looked at.

PMID- 7724062
TI  - Telencephalin: a neuronal area code molecule?
AB  - Cell adhesion molecules (CAMs) with expression restricted to specific
      developmental and structural units of the brain and/or selective neuronal types
      would play critical roles in the formation of functional neuronal networks. In
      this article, we summarize recent progress in knowledge on a brain segment
      specific CAM, telencephalin (TLN). TLN has the following characteristic
      properties. (1) TLN is a neuronal glycoprotein whose expression is restricted
      within telencephalon, the most rostal segment of the brain. (2) TLN is localized
      to the soma-dendritic membrane of subsets of telencephalic neurons, but not to
      the axonal membrane. (3) Abrupt appearance of TLN around birth parallels the
      timing of dendritic development and synapse formation in the telencephalon. (4)
      TLN belongs to the immunoglobulin superfamily and its structure is most closely
      related to intercellular adhesion molecules (ICAMs)-1 and -3. These findings
      suggest that TLN is the first example of dendrite-associated cell adhesion
      molecules (DenCAMs) and that TLN may be involved in the brain segmental
      organization, cell-cell interactions during dendritic development, and
      maintenance of functional neuronal networks. We discuss the possibility that TLN
      is an area code-like address signal that is displayed selectively by
      telencephalic neurons and is decoded by specific subsets of growing axons to make
      proper synaptic connections.

PMID- 7724063
TI  - Blood flow in the sciatic nerve is regulated by vasoconstrictive and vasodilative
      nerve fibers originating from the ventral and dorsal roots of the spinal nerves.
AB  - Anesthetized rats were subjected to repetitive electrical stimulation of either
      the ventral or dorsal root of the spinal nerves between the 11th thoracic and 2nd
      sacral spinal segments. The response of nerve blood flow (NBF) in the sciatic
      nerve was examined using laser Doppler flowmetry. For all nerve fibers
      stimulation was for a 10-30-s period at a supramaximal intensity. (1) Stimulation
      of the T11-L1 ventral roots produced an increase in mean arterial pressure (MAP)
      and a biphasic NBF response was comprised of an initial increase and a subsequent
      decrease. The initial increase was a passive vasodilation due to the increase in
      MAP, while the following decrease in NBF resulted from active vasoconstriction of
      the vasa nervorum due to the activation of sympathetic nerves innervating the
      sciatic vasa nervorum. (2) Stimulation of the ventral root of the L6 segment
      produced an increase in NBF, even though MAP decreased. This increase in NBF was
      apparently mediated by activation of parasympathetic cholinergic vasodilators,
      because the response was abolished by i.v. injection of atropine, a muscarinic
      cholinergic receptor antagonist. (3) Stimulation of the dorsal roots between the
      L3 and S1 segments produced an increase in NBF, independent of changes in MAP.
      This increase in NBF appeared to be mediated by activation of a calcitonin gene
      related peptide (CGRP) containing afferent fibers innervating the vasa nervorum,
      because the response was abolished by topical application of hCGRP (8-37), a CGRP
      receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724064
TI  - Estrogen receptor-immunoreactive neurons contain calcitonin gene-related peptide,
      methionine-enkephalin or tyrosine hydroxylase in the female rat preoptic area.
AB  - We have shown in our previous studies that estrogen treatment selectively
      influences calcitonin gene-related peptide (CGRP)-, methionine-enkephalin (Met
      Enk)- and tyrosine hydroxylase (TH)-immunoreactive (IR) intensities in the
      neurons of the periventricular preoptic nucleus (PPN) and the medial preoptic
      area (MPA) of the female rat. In the present study, we examined whether estrogen
      receptor (ER)-IR neurons in the PPN and MPA contain CGRP, Met-Enk, or TH using a
      double-labeling immunohistochemical method and investigated changes in the number
      of double-labeling cells upon treatment with estrogen. Brain sections of
      ovariectomized rats and ovariectomized and estrogen-treated rat were stained
      using the avidin-biotin-peroxidase complex method followed by the peroxidase-anti
      peroxidase method. The sections were first incubated with an anti-ER antibody in
      conjunction with nickel diaminobenzidine which produces a dark blue reaction
      product in the nucleus. Subsequently, CGRP, Met-Enk or TH antisera were applied
      to these sections and the resulting brown diaminobenzidine reaction product in
      the cytoplasm was examined. Neurons that were double-labeled for ER and CGRP, Met
      Enk or TH were investigated in the PPN and MPA. The number of doubly labeled
      ER/CGRP- and ER/TH-IR neurons was large, whereas the number of ER/Met-Enk-IR
      neurons was small. These results suggest that ER in the PPN and MPA may be more
      closely related to the mechanism of changes in CGRP- and TH-IR intensities upon
      estrogen treatment than that in Met-Enk-IR intensity.

PMID- 7724065
TI  - Pharmacological characterization of serotonin synthesis and uptake suggest a
      false transmitter role for serotonin in the pituitary intermediate lobe.
AB  - A subpopulation of nerve fibers in the rat pituitary intermediate lobe (IL) have
      been shown to exhibit colocalization of serotonin (5-HT-IR) and tyrosine
      hydroxylase immunoreactivities and they are sensitive to neurotoxins specific to
      catecholamine neurons. This study was set out to examine the uptake and synthesis
      mechanisms of serotonin in these fibers. We developed an in vitro technique in
      which the neurointermediate lobe explants were incubated (14 and 48 h) in the
      presence of various drugs and serotonin was subsequently visualized by
      immunohistochemistry. Control incubation in the presence of serotonin (10(-6) M)
      resulted in a rich plexus of 5-HT-IR fibers in both posterior and intermediate
      lobes. Fluoxetine and citalopram (10(-6) M and 10(-5) M), inhibitors of 5-HT
      transporter, did not affect 5-HT-IR in the IL fibers, unless they were used in
      concentrations high enough (10(-4) M and 10(-3) M) to block unspecifically a
      number of monoamine transporters. The same applied for desipramine (10(-5)-10(-7)
      M), an inhibitor of the noradrenaline transporter. However, cocaine (10(-5)-10(
      6) M) blocked serotonin uptake into these terminals, suggesting that serotonin
      uptake occurs through a dopamine transporter. Incubation of the IL in presence of
      L-tryptophan (10(-4) M) did not result in 5-HT-IR in the IL fibers showing
      colocalization of 5-HT-IR and tyrosine hydroxylase, which suggests that these
      fibers do not synthesize serotonin. The present results suggest that serotonin is
      taken up into the IL terminals by a dopamine transporter and is not synthesized
      in them, at least in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724066
TI  - Dopamine modulation of synaptic transmission in rat prefrontal cortex: an in
      vitro electrophysiological study.
AB  - The prefrontal cortex is innervated by a well-defined dopaminergic bundle
      originating from the brainstem and is a key structure in higher order mental
      processes. We have studied the effects of dopamine (DA) on layer V pyramidal
      cells of the prefrontal cortex using intracellular recording in rat brain slices
      maintained in vitro. Bath administration of DA (50-100 microM) had weak effects
      on membrane properties of these neurons. In contrast, DA markedly decreased all
      components of the synaptic responses evoked by electrical stimulation of layer I
      or VI, and in particular the monosynaptic excitatory postsynaptic potential
      (EPSP) which arises from activation of glutamatergic receptors. The afferents
      from layer VI seemed less affected by DA than those from layer I. The NMDA (N
      methyl-D-aspartate) and AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic
      acid) components of monosynaptic EPSPs were equally reduced by DA. The isolated
      fast gabaergic potential (IPSP) resulting from GABAA receptors activation was
      similarly reduced by DA. The suppressive effect of DA on glutamatergic
      transmission was partially mimicked by the D1 receptor agonist SKF 38393 (50
      microM) whereas the D2 receptor agonist quinpirole (50 microM) was ineffective.
      Conversely, this effect was antagonized by the D1 receptor blocker SCH 23390 (100
      microM) but not by the D2 receptor antagonist sulpiride (100 microM). These
      findings indicate that DA decreases both glutamatergic and gabaergic synaptic
      transmission in neurons located in layer V of rat prefrontal cortex. These
      results also suggest that D1 dopamine receptor is involved in the decrement of
      glutamatergic transmission. These interactions between DA and glutamate are
      important in regard to the suspected implications of both neurotransmitters in
      psychiatric diseases.

PMID- 7724067
TI  - Stimulus parameters for induction of long-term depression in in vitro rat
      Purkinje cells.
AB  - Long-term depression (LTD) was induced in rat cerebellar slices by conjunctive
      stimulation of parallel fibers (PFs) and climbing fibers (CFs) under perfusion of
      20 microM picrotoxin. LTD was estimated by the reduction in the initial rising
      slope of EPSPs PF-induced in Purkinje cell dendrites. LTD-inducing efficacy was
      represented by both the average amount of depression and the probability of
      inducing depression greater than 25%, both measured at 40 min after the onset of
      conjunctive stimulation. Using 300 regularly recurring pulses given to both CFs
      and PFs with 0 ms interval, LTD was optimally induced at 1 Hz, and to lesser
      degrees at other frequencies. When the number of conjunctive stimuli at 1 Hz with
      zero CF-PF interval was varied from 50 to 500, 300 stimuli induced LTD most
      robustly. When CF-PF interval was varied while 300 pulses were given at 0.25-4
      Hz, LTD was induced even when PF stimuli were delayed after CF stimuli by as much
      as 2 s, but it was inhibited when PF stimuli preceded CF stimuli by 10-100 ms.
      LTD was also induced by applying repeated short pulse trains to both CFs and PFs,
      but repeated application of a PF stimulus train immediately followed by a CF
      stimulus train as in classical conditioning was effectless. The present results
      suggest complex processes leading to LTD as a result of conjunctive CF and PF
      stimulation.

PMID- 7724068
TI  - Anodal polarization induces protein kinase C gamma (PKC gamma)-like
      immunoreactivity in the rat cerebral cortex.
AB  - Protein kinase C gamma (PKC gamma)-like immunoreactivity was examined in the rat
      brain, employing the monoclonal antibody 36G9 raised against purified PKC gamma,
      after an application of weak anodal direct current to the surface of the
      sensorimotor cortex. Anodal polarization with 3.0 microA for 30 min resulted in a
      pronounced increase in the number of PKC gamma-like-positive neurons in
      accordance with the intensity of PKC gamma-like immunostaining in the neocortex,
      cingulate cortex and piriform cortex ipsilateral to the polarization. The number
      of PKC gamma-like-positive neurons began to increase at 1 h after polarization,
      peaked at 3 h, and thereafter decreased to the control levels by 72 h. The
      increase in expression of PKC gamma-like immunoreactivity in specific areas of
      the cerebral cortex is suggested to serve as a basis for the long-lasting
      hyperexcitability in situ following anodal polarization.

PMID- 7724069
TI  - Mouse fetuses in late gestation maintained in vitro by a transplacental perfusion
      method and their physiological activities.
AB  - The present study demonstrated that live mouse fetuses in late gestation can be
      kept in vitro and their physiological activities maintained for over 24 h.
      Fetuses together with uterus were isolated from pregnant mice at 11.5-17.5 days
      gestation and transplacentally perfused with a physiological solution through a
      cannula inserted into the uterine artery. Under these conditions, various
      physiological activities including heartbeats and spontaneous and stimulation
      induced fetal movements were observed.

PMID- 7724070
TI  - Caring for corpses or killing patients? ... ANA task force responds.

PMID- 7724072
TI  - Managed care contracting: an art or a science?

PMID- 7724071
TI  - Incident reports.

PMID- 7724073
TI  - How to manage in the wired hospital.

PMID- 7724074
TI  - The nurses' agenda: priorities for 1995.

PMID- 7724075
TI  - Pregnancy and the pseudo-diabetic.

PMID- 7724076
TI  - Managed care: whose liability?

PMID- 7724077
TI  - A personal performance checklist.
AB  - Total Quality Management (TQM) principles, practices and tools are used to
      outline a personal checklist. This simple management system allows a manager to
      track undesirable and desirable job performance behaviors and establish a
      proactive, quality-based management style as well as a foundation to effectively
      apply TQM tools.

PMID- 7724078
TI  - A staff-managed ICU.
AB  - After hospital-wide efforts at empowerment, an ICU staff developed and
      implemented a self-governance model. Difficulties included lack of involvement by
      some staff and lack of recognition of the elected Professional Practice Council
      as "director" of ICU. After one year, these problems have been overcome in part.

PMID- 7724079
TI  - Capitation savvy a must.

PMID- 7724081
TI  - Competency assessment: a systematic approach.
AB  - An established clinical development plan was expanded to form a framework for a
      competency assessment model. Each nursing competency has a technical,
      interpersonal and critical thinking component. Behaviors describe all areas from
      novice to expert. The framework identifies and supports a professional model of
      nursing practice.

PMID- 7724080
TI  - Evaluating nursing intensity: it's time to transfer the patient.
AB  - Admission and discharge criteria are important decision-making components.
      Nursing care and management must be considered an imperative part of this
      criteria. The Nursing Evaluation of Nursing Intensity could identify those
      patients that may be passed over under standard admission criteria to Intensive
      Care Units. This tool augments the transfer process as well as helps to determine
      patient location.

PMID- 7724082
TI  - Advanced practice nursing: playing a vital role.
AB  - To clarify the education preparation of advanced practice nurses, a survey of all
      50 states was performed. Results show a high degree of variability from state to
      state in tracking advanced practice nurses. Standardizing the educational
      preparation for the nurse practitioner, clinical nurse specialist, certified
      nurse midwife and the certified registered nurse anesthetist will clarify
      advanced practice nursing.

PMID- 7724083
TI  - Setting up a satellite practice.
AB  - To reach a greater market share, a healthcare facility established two satellite
      practices within the community. This step-by-step process addresses the
      complexities encountered and the services needed when setting up a practice:
      marketing, physician and community participation, physical environment, medical
      service contracts, financial aspects and lease arrangements.

PMID- 7724084
TI  - Analyzing job demands and coping techniques.
AB  - Surviving the stressful days nurses encounter in today's health-care environment
      involves sophisticated coping skills. This qualitative study found nurses
      responded with the use of "I" or "they" approaches to stressful situations.
      Nursing leaders are offered strategies for identifying and relating to these two
      groups of staff.

PMID- 7724085
TI  - Job satisfaction and the 12-hour shift.

PMID- 7724086
TI  - Staff retreats: building a team.

PMID- 7724087
TI  - Leadership from the child within.

PMID- 7724088
TI  - Good intentions pave the road...

PMID- 7724089
TI  - Risk factors for preeclampsia in twin pregnancies: a population-based cohort
      study.
AB  - OBJECTIVE: To evaluate in twin pregnancies the characteristics parity, race,
      smoking, and age, known to be risk factors for preeclampsia in non-twin
      pregnancies. METHODS: All twin pregnancies (3407) and approximately twice as many
      singletons (8287) were assembled using Washington state birth certificates from
      the period 1984-1988. RESULTS: In singleton pregnancies, preeclampsia was more
      common in women who were younger, black, poor, nulliparous, and nonsmokers. In
      twin pregnancies, similar associations were found, but were only statistically
      significant for age, race, and parity. There were no significant differences in
      the risk factors between twin and singleton women. Logistic regression showed
      that twin pregnancy carries a relative risk (RR) of 3.5 (95% confidence interval
      [CI] 3.0-4.2), nulliparity an RR of 4.0 (95% CI 3.3-4.8), and black race an RR of
      1.8 (95% CI 1.2-2.6) for preeclampsia. In each case, this risk is independent of
      the other risk factors. CONCLUSION: Twin pregnancy carries nearly a fourfold
      increased risk of preeclampsia, independent of race and parity, and the risk of a
      nulliparous twin pregnancy is 14 times that of a parous singleton pregnancy. Risk
      factors in a singleton pregnancy act similarly in a twin pregnancy. Thus, any
      pathophysiologic model for preeclampsia needs to account for the risk twin
      pregnancy poses as well as other risk factors, such as parity and race.

PMID- 7724090
TI  - Ability of normal vaginal flora to produce detectable phosphatidylglycerol in
      amniotic fluid in vitro.
AB  - OBJECTIVE: To determine if bacteria are capable of producing phosphatidylglycerol
      in amniotic fluid (AF) and the number of colony forming units (CFU) of bacteria
      necessary to produce this result. METHODS: Eleven species of bacteria and one
      species of yeast, common to the female genital tract and implicated in
      chorioamnionitis, were selected. Amniotic fluid was collected from 21 women and
      inoculated with 10(8) CFU/mL of each isolate. Aliquots of AF were tested at 0, 4,
      12, and 24 hours for colony counts and the presence of phosphatidylglycerol by
      thin-layer chromatography. RESULTS: The mean gestational age (+/- standard
      deviation) of the 21 study patients was 33 weeks and 1 day (+/- 4 weeks). Among
      the 12 species studied, Escherichia coli produced phosphatidylglycerol, at a
      concentration of 1.75 x 10(8) CFU/mL, beginning 12 hours after incubation.
      CONCLUSION: Escherichia coli is capable of producing phosphatidylglycerol in AF
      in vitro and is present in the vagina in 24% of normal pregnant patients. Our
      findings question the validity of using vaginal pool AF specimens for
      phosphatidylglycerol determination. Therefore, we recommend that patients
      presenting with preterm premature rupture of membranes be evaluated by
      amniocentesis to determine fetal lung maturity with phosphatidylglycerol and the
      lecithin-sphingomyelin ratio.

PMID- 7724091
TI  - The relationship between peak velocity in the fetal descending aorta and
      hematocrit in rhesus isoimmunization.
AB  - OBJECTIVE: To correlate the peak velocity in the fetal descending aorta, as
      measured by pulsed Doppler ultrasound, with fetal hematocrit values assessed by
      funipuncture in pregnancies complicated by rhesus isoimmunization. METHODS: One
      hundred twelve consecutive funipunctures were performed on 33 rhesus-negative
      gravidas of 21-36 weeks' gestation (median 30). Doppler flow, corrected for
      angle, was measured on the fetal descending aorta with pulsed Doppler equipment
      immediately before funipuncture. Differences between observed peak velocities and
      the calculated gestational age-dependent upper confidence limits (delta peak
      velocities) were compared with corresponding differences between observed
      hematocrits and the calculated lower confidence limits (delta hematocrits), and a
      regression analysis on the above paired difference values was performed. In
      addition, the correlation coefficient between delta peak velocities and delta
      hematocrits was calculated for the first procedure per pregnancy only. RESULTS:
      The mean peak aortic velocity of anemic fetuses was higher than that of
      unaffected fetuses (P < .001); delta peak aortic velocities correlated negatively
      with delta hematocrits (r = -0.66, P < .001). The correlation coefficient between
      delta peak aortic velocities and delta hematocrits for the first procedure peer
      pregnancy only was r = -0.72 (P < .001). Prediction of fetal anemia by Doppler
      using gestational age-dependent 95% confidence limits was possible with positive
      and negative predictive values of 73 and 66%, respectively. CONCLUSION: Peak
      aortic velocity, a noninvasive assessment of fetal anemia, may be used as an
      additional test for monitoring pregnancies complicated by rhesus isoimmunization.
      However, the limited predictive capacity hampers its clinical usefulness.

PMID- 7724092
TI  - Peak velocity of the outflow tract of the aorta: correlations with acid base
      status and oxygenation of the growth-retarded fetus.
AB  - OBJECTIVE: To correlate the peak velocities of the aortic outflow tract of growth
      retarded fetuses with fetal acid base status and oxygenation measured in utero.
      METHODS: Thirty-one growth-retarded fetuses with abnormal umbilical pulsatility
      index (PI) measurements underwent fetal blood sampling. Blood pH, carbon dioxide
      pressure (PCO2), oxygen pressure (PO2), oxygen saturation, lactate concentration,
      and hemoglobin concentration were measured. Using color Doppler equipment, we
      measured the peak velocities of the outflow tract of the aorta, pulmonary artery,
      and ductus arteriosus before fetal blood sampling. RESULTS: The peak velocities
      measured in the outflow tract of the aorta, pulmonary artery, and ductus were
      significantly lower in growth-retarded fetuses than in 140 normal fetuses of
      comparable weight. The correlation observed between pulmonic and aortic peak
      velocities was significant (r = 0.84), as was that between pulmonic and ductal
      peak velocities (r = 0.74). Growth-retarded fetuses with abnormal aortic peak
      velocities had significantly lower values of PO2, oxygen content and pH, and had
      higher lactate concentration and PCO2 than did growth-retarded fetuses with
      normal peak velocities. Estimated fetal weight and umbilical PI (mean +/-
      standard deviation) were not significantly different in these two groups.
      Moreover, significant direct correlations were found between proximal aortic peak
      velocities and lactate concentrations (correlation coefficient 0.71, P < .0001)
      and O2 content (P < .02, r = 0.42). CONCLUSION: For growth-retarded fetuses,
      Doppler peak velocity in these vessels is significantly lower than in normal
      fetuses of comparable weight. Aortic, pulmonic, and ductal peak velocity
      correlated significantly. Growth-retarded fetuses with abnormally low peak
      velocity in the outflow tract of the aorta have a higher risk of acidemia and
      hypoxia than those with normal velocities.

PMID- 7724093
TI  - Fetal response to carbon dioxide pneumoperitoneum in the pregnant ewe.
AB  - OBJECTIVE: To determine the effects of maternal abdominal carbon dioxide (CO2)
      insufflation on placental blood flow and fetal blood gas measurements in the
      pregnant ewe. METHOD: Five time-bred ewes at 110 days' gestation were surgically
      prepared with maternal and fetal catheters placed for subsequent measurement of
      vascular pressures, blood gas tensions, and placental blood flows. On surgical
      recovery day 3, the ewe was anesthetized, placed on her right side, intubated,
      and manually ventilated to maintain a constant maternal carbon dioxide pressure
      (PCO2) range (37.1 +/- 3.3 mmHg) for the duration of the experiment. The maternal
      abdomen was inflated with CO2 to maintain an intraabdominal pressure of 20.7 +/-
      0.6 mmHg. Maternal and fetal blood flows and blood gases were determined at 30
      minutes of ventilation, 60 minutes of insufflation, and 40 minutes of
      desufflation. Simultaneous maternal and fetal organ blood flows were determined
      using the radioactive microsphere technique. RESULTS: Maternal perfusion pressure
      fell 22% (P = .01) in response to insufflation, whereas pressure in the inferior
      vena cava rose 53% (P = .003). Maternal placental blood flow fell to 61% (P =
      .002) of control. Seventy-seven percent of this blood-flow change was in response
      to the decreased perfusion pressure, with 23% resulting from an increased
      placental vascular resistance of 32% (P = .02). Maternal blood gas values did not
      change with insufflation or desufflation. Despite the marked decrease in maternal
      placental blood flow, the fetal placental perfusion pressure and blood flow, pH,
      and blood gas tensions were unaffected by insufflation or desufflation.
      CONCLUSION: The sheep fetus has sufficient placental flow reserves or
      compensatory responses to maintain adequate gas exchange during a 1-hour, 20 mmHg
      maternal pneumoperitoneum. Laparoscopic surgical procedures may prove to be a
      safe alternative to laparotomy during pregnancy.

PMID- 7724094
TI  - The impact of knowledge of human immunodeficiency virus serostatus on
      contraceptive choice and repeat pregnancy.
AB  - OBJECTIVE: To examine relationships among human immunodeficiency virus (HIV)
      serostatus, postpartum contraceptive choice, and the rate of repeat pregnancy
      within a short interval. METHODS: This retrospective cohort study was performed
      in 83 seropositive and 218 seronegative women identified from an inner-city
      prenatal population undergoing routine voluntary HIV antibody screening from July
      1987 through June 1989. Postpartum contraceptive choices and rate of repeat
      pregnancies were compared based on HIV serostatus. RESULTS: Seropositive women
      were significantly more likely than seronegative women to undergo tubal
      sterilization (27 versus 15%; odds ratio [OR] 2.9, 95% confidence interval [CI]
      1.5-5.9). This relationship persisted after controlling for age, race, marital
      status, and parity by logistic regression modeling (adjusted OR 2.9, 95% CI 1.4
      5.9). Seropositive women were significantly less likely than seronegative women
      to select oral contraceptives (34 versus 68%; OR 0.2, 95% CI 0.1-0.4), a
      relationship that persisted after controlling for age, race, marital status,
      parity, and foam and condom use (adjusted OR 0.2, 95% CI 0.1-0.5). Seropositive
      women were significantly more likely than seronegative women to select foam and
      condoms as their primary method of contraception (30 versus 15%; OR 2.4, 95% CI
      1.2-4.5), a relationship that did not persist after controlling for age, race,
      marital status, and parity (adjusted OR 0.7, 95% CI 0.4-1.3). The risk of repeat
      pregnancy was slightly lower in seropositive versus seronegative women (34 versus
      44%; OR 0.7, 95% CI 0.4-1.3). Most repeat pregnancies among seropositive and
      seronegative women were unplanned (90 and 82%, respectively). CONCLUSION: There
      was a relationship between the method of postpartum contraception and HIV
      serostatus, but no significant difference in repeat pregnancy rates associated
      with choice of method.

PMID- 7724095
TI  - Human papillomavirus infection in human immunodeficiency virus-seropositive
      women.
AB  - OBJECTIVE: To compare the prevalence of human papillomavirus (HPV) infections in
      women who are seropositive and seronegative for human immunodeficiency virus
      (HIV), and to determine if associations between HPV and cervical disease are
      altered in HIV-seropositive women. METHODS: In this cross-sectional study, 344
      HIV-seropositive and 325 HIV-seronegative women underwent colposcopy and HPV DNA
      testing. RESULTS: Human immunodeficiency virus-seropositive women were more
      likely than HIV-seronegative women to have HPV DNA of any type detected (60
      versus 36%, P < .001). Infections with HPV type 16 (27 versus 17%, P < .05), type
      18 (24 versus 9%, P < .05), and more than one type of HPV (51 versus 26%, P <
      .05) were also more common in HIV-positive women. Although both latent HPV
      infection and HPV infections associated with cervical intraepithelial neoplasia
      (CIN) were more prevalent in the HIV-seropositive group, the ratio between these
      two types of infections was altered markedly in the HIV-seropositive women. Human
      immunodeficiency virus-seropositive women who were HPV-infected were
      significantly more likely to have CIN than were HPV-infected HIV-seronegative
      women, an increase observed at all levels of immunosuppression. Analysis of
      specific HPV types associated with latent HPV infection and CIN indicated that
      HIV seropositivity only minimally alters the known associations between specific
      types of HPV and cervical disease. CONCLUSION: Human papillomavirus infections
      are more common among HIV-seropositive women at all levels of immunosuppression.
      However, relationships between HIV and HPV are complex and cannot be explained
      completely by an increased susceptibility to new HPV infections in the
      immunosuppressed patient.

PMID- 7724096
TI  - Reduction of pain and nausea after laparoscopic sterilization with bupivacaine,
      metoclopramide, scopolamine, ketorolac, and gastric suctioning.
AB  - OBJECTIVE: To determine whether postoperative pain and nausea after laparoscopic
      sterilization can be reduced with a combination of bupivacaine, metoclopramide,
      scopolamine, ketorolac, and gastric suctioning. METHODS: Women undergoing
      outpatient laparoscopic sterilization were randomized to protocol management or
      nontreatment groups. Each patient received standard general endotracheal
      anesthesia. Protocol subjects received intramuscular ketorolac 60 mg and
      scopolamine 0.25 mg, intravenous metoclopramide 10 mg, and gastric suctioning;
      bupivacaine (2.5 mg/mL) with epinephrine (5 micrograms/mL) was injected at trocar
      sites and dripped onto the fallopian tubes. The nontreatment group served as
      controls. Visual analogue scales were used to evaluate pain and nausea (measured
      in millimeters). Demographic characteristics, postoperative requirements for
      analgesics and antiemetics, time to discharge, and unscheduled admission were
      also evaluated. RESULTS: During a 7-month period, 71 women were enrolled.
      Protocol subjects (N = 35) reported pain severity of 27.9 +/- 19.1 mm (mean +/-
      standard deviation), whereas controls (N = 36) reported 59.3 +/- 23.3 mm (P <
      .001). Fourteen protocol patients requested additional pain medication, compared
      with 29 controls (P < .001). Protocol patients indicated a nausea severity of 9.9
      +/- 18.7 mm, whereas the controls reported 38.8 +/- 35.5 mm (P < .001). Only one
      protocol patient required nausea medication, compared with nine controls (P <
      .02). Severity of pain correlated with severity of nausea (r = 0.38166, P <
      .001). Protocol patients were discharged from the outpatient surgery unit in
      148.6 +/- 45.0 minutes, compared with 176.4 +/- 58.5 minutes for controls (P <
      .03). CONCLUSION: This regimen reduced the severity of pain and nausea after
      outpatient laparoscopic sterilization. The need for additional analgesics and
      antiemetics was also reduced. Protocol patients were discharged earlier than
      controls. These benefits seem to accrue without significant risk. We believe that
      this regimen may also be useful in other ambulatory laparoscopic procedures.

PMID- 7724097
TI  - A randomized trial of prophylactic doxycycline for curettage in incomplete
      abortion.
AB  - OBJECTIVE: To determine whether prophylactic doxycycline at suction curettage for
      incomplete abortion decreases the rate of postoperative pelvic infection.
      METHODS: We randomized 240 patients to receive intravenous doxycycline or placebo
      at curettage. Cervical specimens for gonorrhea and chlamydia were obtained
      preoperatively. Two weeks post-procedure, we evaluated all patients for
      infectious morbidity and repeated gonorrhea and chlamydia cultures. Statistical
      analysis used Mann-Whitney U test, McNemar test, or Fisher exact test, as
      appropriate. RESULTS: There were no statistically significant differences in age,
      parity, gestational age, history of sexually transmitted disease, pelvic
      inflammatory disease, or multiple sex partners between the doxycycline and
      placebo groups. Preoperative gonorrhea or chlamydia isolates were positive in
      five (4.2%) and six (5%) of 120 doxycycline patients and four (3.3%) and eight
      (6.6%) of 120 controls (not significant). All preoperative gonorrhea isolates
      remained positive postoperatively. Seven (5.8%) controls had positive
      postoperative chlamydia isolates, as did one (0.8%) in the doxycycline group (P =
      .06). We diagnosed eight (6.6%) of 120 doxycycline patients and seven (5.8%) of
      120 controls with infectious morbidity (not significant). CONCLUSION: In our
      population of patients with incomplete abortion, the prevalence of gonorrhea and
      chlamydia was low, and prophylactic doxycycline did not decrease the rate of
      postoperative febrile morbidity.

PMID- 7724098
TI  - Second-trimester abortion by intramuscular 15-methyl-prostaglandin F2 alpha or
      intravaginal prostaglandin E2 suppositories: a randomized trial.
AB  - OBJECTIVE: To compare intramuscular (IM) prostaglandin 15 methyl-F2 alpha (15M
      PGF2 alpha) with prostaglandin E2 (PGE2) vaginal suppositories for second
      trimester abortion in terms of efficacy and side effects. METHODS: Fifty-one
      women were randomized to receive either 15M-PGF2 alpha IM injections or PGE2
      intravaginal suppositories for second-trimester abortion. Efficacy and side
      effects of the two agents were analyzed by two-tailed t tests, chi 2 analysis
      with Fisher exact test, and survival analysis. RESULTS: The mean times to rupture
      of membranes, delivery of fetus, and delivery of placenta were significantly less
      for women receiving PGE2 vaginal suppositories. The cumulative abortion rate
      after 24 hours for the PGE2 group was 96%, compared with 69% for the 15M-PGF2
      alpha group. Although there were few differences in side effects, the 15M-PGF2
      alpha group had significantly fewer headaches, fevers, and chills. CONCLUSION:
      Intravaginal PGE2 is superior to IM 15M-PGF2 alpha for second-trimester abortion.

PMID- 7724099
TI  - Placenta accreta encountered during dilation and evacuation in the second
      trimester.
AB  - OBJECTIVE: To assess the frequency of placenta accreta encountered during
      dilation and evacuation (D&E) in the second trimester. METHODS: Among 16,827
      second-trimester D&E procedures performed at our hospitals and clinics, seven
      cases of placenta accreta, either suspected clinically or proven histologically,
      were encountered. These cases were analyzed for history of prior cesarean
      delivery, placenta localization, and histology of hysterectomy specimens.
      RESULTS: Six of the seven cases suspected clinically were confirmed
      histologically. All placenta accreta patients had at least one cesarean delivery
      (mean 1.7), and five had a preoperative sonogram demonstrating some form of
      placenta previa. The prevalence of clinical placenta accreta encountered during
      D&Es in the second trimester was 0.04%, the same as that reported for placenta
      accreta diagnosed clinically in the third trimester. CONCLUSION: Placenta accreta
      can be a potential complicating factor in the patient undergoing D&E in the
      second trimester.

PMID- 7724100
TI  - A comparison of stress leak-point pressure and maximal urethral closure pressure
      in patients with genuine stress incontinence.
AB  - OBJECTIVE: To determine the correlation between the maximal urethral closure
      pressure and the stress leak-point pressure in patients with genuine stress
      incontinence, and to define a critical stress leak-point pressure value to detect
      patients with a low-pressure urethra, as defined by a maximal urethral closure
      pressure less than 20 cm H2O. METHODS: Fifty-nine patients with genuine stress
      incontinence were evaluated prospectively with multichannel urodynamics. Maximal
      urethral closure pressures and stress leak-point pressures were determined and
      correlated. Several stress leak-point pressure values were evaluated by
      contingency tables to detect a critical level for detecting a low-pressure
      urethra. RESULTS: There is a statistically significant relationship (P < .0001)
      between the stress leak-point pressure and the maximal urethral closure pressure.
      However, a correlation coefficient of 0.56 demonstrates poor clinical
      relationship. A stress leak-point pressure less than or equal to 45 cm H2O was
      found to be 80% sensitive and 90% specific in diagnosing a low-pressure urethra.
      A stress leak-point pressure less than or equal to 60 cm H2O was 90% sensitive
      and 64% specific in detecting a low-pressure urethra. CONCLUSIONS: The stress
      leak-point pressure has poor clinical correlation to the maximal urethral closure
      pressure. A stress leak-point pressure less than or equal to 45 cm H2O has
      adequate sensitivity and specificity to diagnose a low-pressure urethra. A value
      less than or equal to 60 cm H2O would be an appropriate cutoff level to screen
      for those patients at risk of having a low-pressure urethra in need of further
      evaluation.

PMID- 7724101
TI  - Prognostic significance of human papillomavirus DNA in vulvar carcinoma.
AB  - OBJECTIVE: To determine the histopathologic, epidemiologic, and prognostic
      significance of human papillomavirus (HPV) DNA in primary invasive vulvar cancer.
      METHODS: From December 1981 through October 1992, primary tumor tissue from 55
      newly diagnosed vulvar cancers was evaluated for the presence of HPV DNA. The DNA
      was extracted from tumor tissue and subjected to the polymerase chain reaction
      (PCR) using highly conserved consensus L1 primers that detect 25 different HPV
      genotypes and primers specific for HPV type 6/E6, type 16/E7, and type 18/E6 gene
      sequences. All PCR products were hybridized to type-specific radiolabeled probes.
      The association between the presence of HPV DNA and histologic, epidemiologic,
      and clinical characteristics was analyzed. RESULTS: Thirty-three (60%) tumors
      contained HPV DNA. Patients younger than 70 years of age or who smoked were more
      likely to have HPV-positive vulvar cancers. Twenty-one (95%) of 22 tumors
      classified as basaloid, warty, or verrucous contained HPV DNA, whereas 12 (39%)
      of 31 typical squamous tumors contained HPV (P < .001). Two adenocarcinomas were
      negative for HPV. Tumors with or without HPV DNA did not differ with respect to
      International Federation of Obstetricians and Gynecologists stage (size and nodal
      status), tumor grade, or therapy. Using life-table analysis, the absence of HPV
      DNA and the presence of regional nodal metastasis were predictive of recurrence
      and death from vulvar cancer. When controlling for lesion size, age, tumor grade,
      and nodal metastasis using the Cox proportional hazards model, only HPV status
      remained an independent prognostic factor. CONCLUSION: Human papillomavirus DNA
      is more common in vulvar cancers of young women who smoke than in older
      nonsmokers. Patients with HPV-negative tumors are at an increased risk of
      recurrence and death from vulvar cancer.

PMID- 7724102
TI  - Low-grade Papanicolaou smears and the Bethesda system: a prospective
      cytohistopathologic analysis.
AB  - OBJECTIVE: To examine the clinical usefulness of the Bethesda classification
      system of low-grade cervicovaginal cytology as it relates to predicting
      underlying histology and aiding in triage to colposcopy. METHODS: We evaluated
      1454 women with abnormal cytologic screening results: 782 with atypical squamous
      cells of uncertain significance (atypia), 355 with low-grade squamous
      intraepithelial lesions (SIL) determined by the presence of human papillomavirus
      (HPV) alone, and 317 with low-grade SIL determined by the presence of cytologic
      evidence of mild dysplasia (cervical intraepithelial neoplasia [CIN] I) devoid of
      HPV cytopathologic features. All women underwent colposcopy, directed-punch
      biopsy or loop electrosurgical excision, and/or endocervical curettage (ECC), as
      indicated. RESULTS: Women from the low-grade SIL-CIN I referral cytology group
      were significantly more likely to harbor all grades of biopsy-proven dysplasia
      than were those from the atypical squamous cells of uncertain significance and
      low-grade SIL-HPV groups, which showed no statistical differences. CONCLUSIONS:
      Contrary to the Bethesda system, which combines CIN I and HPV changes because of
      cytomorphologic similarities, this study suggests that patients with HPV
      cytologic smears are similar to patients with atypical smears and are less likely
      to harbor any biopsy-proven CIN lesions than are patients with CIN I
      cervicovaginal smears. If excluded from colposcopic triage, approximately 5% of
      patients with atypical cytologic smears from a well-screened population similar
      to ours will harbor high-grade lesions that may progress during any waiting
      period. Triage of low-grade cervicovaginal smears based on histopathologic
      correlation is encouraged.

PMID- 7724103
TI  - HER-2/neu, p53, and DNA analyses as prognosticators for survival in endometrial
      carcinoma.
AB  - OBJECTIVE: To compare the prognostic importance of certain molecular biologic
      characteristics (HER-2/neu and p53 gene overexpression, DNA ploidy, and the S
      phase fraction) to standard clinical-pathologic factors used to predict survival
      in patients with endometrial carcinoma. METHODS: We reviewed archival specimens
      from 128 patients with endometrial cancer diagnosed during the period 1985-1987.
      One hundred four cases were eligible for inclusion in the study.
      Immunohistochemistry was used to detect p53 and HER-2/neu overexpression. We used
      flow cytometry to calculate DNA ploidy and the S-phase fraction. Life-table
      analysis and Cox multiple regression were used to analyze clinical and molecular
      data with respect to survival. RESULTS: International Federation of Obstetrics
      and Gynecology stage, nuclear grade, lymph-vascular space invasion, and adverse
      histopathologic features each significantly correlated with poor outcome (each at
      P < or = .001). Overexpression of p53 was demonstrated in 15% of the tumors and
      was associated with a 12% probability of 5-year survival, compared to a 90%
      probability of 5-year survival for the p53-negative cohort (P = .0001). Thirty
      percent of the tumors were aneuploid, which was also associated with poor
      prognosis (P = .0003). HER-2/neu overexpression and an S-phase fraction greater
      than 10% showed similar trends, but were not statistically significant. On
      multivariate analysis, p53 overexpression was the strongest independent
      prognosticator of survival (P = .0001). CONCLUSION: Molecular characteristics
      provide objective data that may be useful in predicting prognosis in patients
      with endometrial cancer. Further investigation of molecular and genetic
      characteristics are needed to refine our diagnostic and treatment modalities.

PMID- 7724104
TI  - Ovarian malignant mixed mullerian tumors treated with platinum-based
      chemotherapy.
AB  - OBJECTIVE: To characterize the clinical course of patients diagnosed with ovarian
      malignant mixed mullerian tumors treated with platinum-based chemotherapy.
      METHODS: Thirty-six patients received this treatment at The University of Texas
      M. D. Anderson Cancer Center in the period 1979-1993. The mean age was 59 years.
      Stage distribution was as follows: stage IA, one (3%) patient; stage IIIB, two
      (5.5%); stage IIIC, 21 (58%); and stage IV, two (5.5%). Ten (28%) patients were
      unstaged. Chemotherapy regimens included cisplatin, doxorubicin, and
      cyclophosphamide in 16 patients; cisplatin-ifosfamide in five; cisplatin
      cyclophosphamide in four; carboplatinum in three; cisplatin-doxorubicin in three;
      and various other combinations in the remaining five. RESULTS: Of 16 patients
      evaluated for clinical response, seven (44%) had a complete response and four
      (25%) had a partial response, for a total clinical response rate of 69%. Nine
      patients were evaluated for surgical response: five (56%) had a complete response
      and one (11%) had a partial response, for a total surgical response rate of 67%.
      The median survival for the cohort was 18 months. At the time of this analysis,
      five (14%) patients were alive and disease-free, 25 (69%) had died of disease,
      five (14%) were alive with disease, and one had been lost to follow-up.
      CONCLUSION: This study suggests that the clinical course of patients with ovarian
      malignant mixed mullerian tumors treated with platinum-based chemotherapy is
      similar to the clinical course experienced by patients with high-grade epithelial
      carcinoma of the ovary.

PMID- 7724105
TI  - Atrial natriuretic factor in gynecologic malignancy.
AB  - OBJECTIVE: To determine whether plasma atrial natriuretic factor (ANF) levels are
      different in patients with gynecologic malignancy compared with those in healthy,
      nonpregnant women, and if differences do exist, whether chemotherapy plays a
      role. METHODS: We compared the plasma levels of ANF in nonpregnant women free of
      malignancy (group 1, n = 25) and in patients with malignancy receiving at least
      one course of platinum-based chemotherapy (group 2, n = 32). To differentiate the
      contributory role of chemotherapy, another group of patients (group 3, n = 18)
      was studied before the initiation of chemotherapy. RESULTS: The ANF values (mean
      +/- standard error [SE]) in groups 1, 2, and 3 were 7.3 +/- 0.3, 13.8 +/- 0.8,
      and 14.6 +/- 1.8 fmol/mL of plasma, respectively. Significant differences (P < or
      = .001) occurred between groups 1 and 2 and 1 and 3, but not between 2 and 3. In
      comparing groups 2 and 3 for a specific type of cancer, there were no significant
      differences. The respective values (mean +/- SE) for endometrial, ovarian, and
      cervical cancer before chemotherapy were 9.9 +/- 1.7, 15.05 +/- 2.6, and 18.5 +/-
      4.3 fmol/mL. After chemotherapy, the values remained at 9.3 +/- 1.5, 15.03 +/-
      1.06, and 14.6 +/- 2.2 fmol/mL, respectively. CONCLUSION: Plasma ANF levels in
      gynecologic cancer patients were significantly higher than those in healthy,
      nonpregnant women. Levels were higher before chemotherapy started, thus negating
      the idea that chemotherapy may initiate the production and release of ANF.

PMID- 7724106
TI  - The correlation between transperineal sonography and digital examination in the
      evaluation of the third-trimester cervix.
AB  - OBJECTIVE: To determine the correlation between transperineal or translabial
      ultrasound and digital examination of the cervix in the third trimester in women
      presenting to the obstetrical triage area complaining of uterine contractions
      and/or rupture of membranes. METHOD: One hundred women were evaluated initially
      with an ultrasound unit using a 5-MHz glove-covered curvilinear transducer
      applied to the perineum in the sagittal plane. Immediately after the ultrasound
      evaluation, another examiner assessed the cervix digitally, blinded to the
      sonographic results. Cervical dilatation, length, and station were assessed.
      RESULTS: Transperineal ultrasound correlated (P < .001) with digital cervical
      examination in the assessment of dilatation (Pearson correlation coefficient
      0.87), length (Pearson correlation coefficient 0.80), and corrected station
      (Pearson correlation coefficient 0.69). CONCLUSION: There is a statistically
      significant correlation between the digital cervical examination and the
      sonographic assessment of cervical dilatation, length, and station by the
      transperineal approach.

PMID- 7724107
TI  - Epidural analgesia and uterine function.
AB  - OBJECTIVE: To determine whether continuous epidural analgesia with bupivacaine
      and fentanyl affects the rate of cervical dilation and myometrial contractility.
      METHODS: In a 5-week period, 62 consecutive women who received standardized
      epidural analgesia were matched with the next two groups of 124 consecutive women
      of the same parity who did not receive epidural analgesia. The outcome variables
      were uterine activity, rate of cervical dilation, oxytocin therapy, and operative
      deliveries. RESULTS: Continuous epidural analgesia with bupivacaine and fentanyl
      did not result in a change in myometrial contractility in the first hour after
      the initiation of analgesia. However, despite more oxytocin therapy, the rate of
      cervical dilation was significantly lower in the epidural group than in the
      nonepidural group (1.9 versus 5.6 cm/hour, P < .001). Operative deliveries were
      more common in patients with epidural analgesia than in those without it (12 of
      62 versus two of 124, P < .001). CONCLUSION: After epidural analgesia, myometrial
      contractility is maintained with oxytocin, but the ability of the uterus to
      dilate the cervix is reduced significantly.

PMID- 7724108
TI  - The effect of multifetal pregnancy reduction on serum relaxin.
AB  - OBJECTIVE: To determine the effect of multifetal pregnancy reduction on
      circulating relaxin levels. METHODS: Patients with multifetal pregnancies had
      relaxin levels determined on the day of multifetal pregnancy reduction, after the
      procedure, and late in pregnancy. RESULTS: Forty-eight women (26 presenting with
      three fetuses and 22 with four or more) were studied. All pregnancies followed
      some form of ovulation induction. All pregnancies (except for one, which was
      reduced to a singleton) were reduced to twins. Pre-procedure, post-procedure and
      late-pregnancy relaxin levels were significantly higher in the in vitro
      fertilization (IVF)-gamete intrafallopian transfer (GIFT) group compared with the
      human menopausal gonadotropin (hMG)-alone group (P < .05). The initial number of
      fetuses had no significant effect on relaxin levels. Although post-procedure
      relaxin levels were significantly lower than pre-procedure levels (P = .002),
      relaxin levels continued to decrease throughout pregnancy, as evidenced by even
      lower levels later on (P = .0001). CONCLUSIONS: Serum relaxin levels were
      significantly higher in the IVF-GIFT group than in the hMG-alone group, which
      probably reflects more aggressive ovulation induction in the former. Because
      relaxin levels continued to decrease throughout pregnancy, the difference
      observed between pre- and post-procedure levels are not considered to be due to
      the procedure itself.

PMID- 7724109
TI  - Uterine artery Doppler velocimetry in relation to trophoblast migration into the
      myometrium of the placental bed.
AB  - OBJECTIVE: To test the hypothesis that an abnormally high resistance in the
      uterine artery indicates impaired trophoblast migration into the myometrium of
      the placental bed. METHODS: Doppler velocimetry in the uterine artery was carried
      out in 43 pregnant women within 7 days before cesarean delivery and placental bed
      biopsy. A pathologist evaluated the placental bed biopsies histologically.
      Trophoblast migration was absent in 28 cases (impaired migration group) and
      present in 15 (migration group). Clinical characteristics were compared between
      these two groups. RESULTS: There was no significant difference in the mean
      gestational ages at delivery in the two groups, but those with impaired migration
      included a higher incidence of small for gestational age infants (46.4 versus
      6.7%, P < .01) and a lower mean (+/- standard deviation) birth weight (1622 +/-
      528 versus 2287 +/- 748 g, P < .01). The systolic-diastolic ratio (S/D) in the
      uterine artery was higher in the impaired migration group (2.45 +/- 0.81 versus
      1.92 +/- 0.34, P < .05). The absence of migration could be deduced from the S/D
      of the uterine artery, with a predictive value of 92.3% when we set the cutoff
      value of the ratio at 2.5. CONCLUSION: The results suggest that abnormal uterine
      artery flow velocity waveforms may indicate impaired trophoblast migration into
      the myometrium of the placental bed.

PMID- 7724110
TI  - Comparison of 12- and 72-hour expectant management of premature rupture of
      membranes in term pregnancies.
AB  - OBJECTIVE: To compare 12-hour and 72-hour expectant management of premature
      rupture of membranes (PROM) in singleton term pregnancies. METHODS: In a
      prospective, nonrandomized study, 566 low-risk women with singleton term
      pregnancies presenting with PROM were assigned to either 12-hour or 72-hour
      expectant management. Patients who had not entered labor at the end of the
      assigned period were induced with oxytocin. The pregnancy outcome of both methods
      was compared with regard to infectious complications and method of delivery.
      RESULTS: There was no statistical difference in the rate of chorioamnionitis
      between the 12-hour and 72-hour expectant management groups (11.7 versus 12.7%;
      relative risk [RR] 0.9, 95% confidence interval [CI] 0.6-1.5; P = .83). Cesareans
      were performed to a similar degree in both groups (4.7 versus 6.7%; RR 0.7, 95%
      CI 0.3-1.4; P = .39). Fifty-five percent of the 12-hour group underwent oxytocin
      induction, compared with 17.5% of those in the 72-hour group (RR 5.8, 95% CI 3.9
      8.5; P < .001). Women undergoing induction after 72-hour expectant management had
      an increased risk of cesarean delivery compared with those after a 12-hour wait
      (RR 5.9, 95% CI 2.3-15.1; P < .001). Overall, women in the 12-hour group had
      shorter admission-to-discharge times than the 72-hour group (5 versus 6 days, 95%
      CI of the difference 0.6-1.3; P < .01). CONCLUSION: Regimens of 12-hour and 72
      hour expectant management of PROM are comparable regarding infectious
      complications and pregnancy outcome. However, the longer wait prolongs the
      interval to delivery and increases hospitalization costs.

PMID- 7724111
TI  - Outpatient oral sulindac to prevent recurrence of preterm labor.
AB  - OBJECTIVE: To assess the efficacy and safety of oral sulindac in preventing the
      recurrence of preterm labor. METHODS: This was a randomized, double-blind,
      placebo-controlled study of patients between 24-34 weeks' gestation with preterm
      labor treated with intravenous magnesium sulfate. After successful tocolysis,
      patients were randomized by the pharmacy to receive either oral sulindac (200 mg)
      or placebo (once orally every 12 hours) for 7 days. RESULTS: Sixty-nine patients
      were enrolled (34 in the sulindac group, 35 controls). No significant differences
      were found with respect to time gained in utero (40 +/- 4.4 versus 31 +/- 3.4
      days, P = .1), delivery at more than 35 weeks' gestation (20 versus 18, P = .70),
      recurrent preterm labor (11 versus 13, P = .88), birth weight (2528 +/- 646
      versus 2459 +/- 707 g, P = .68), or time spent in the neonatal intensive care
      unit (4.2 +/- 12.9 versus 5.7 +/- 13.5 days, P = .63) for the sulindac and
      control groups, respectively. However, in women who failed therapy (ie, those who
      delivered before 37 weeks' gestation or required readmission for tocolysis),
      there was a significantly longer interval between the start of therapy and
      failure in the sulindac group (25.9 +/- 3.4 days, n = 26) than in the control
      group (15.2 +/- 2.8 days, n = 25; P < .05). CONCLUSION: The use of oral sulindac
      for 1 week after successful parenteral tocolysis failed to reduce the overall
      rate of preterm birth. In women who delivered prematurely or required readmission
      for tocolysis, oral sulindac significantly prolonged the interval from the start
      of therapy until delivery or readmission. Moreover, this benefit was achieved
      without observable adverse effects on the fetus.

PMID- 7724112
TI  - Postpartum ovarian vein thrombosis after vaginal delivery: a report of 11 cases.
AB  - OBJECTIVE: To review and characterize the presentation of postpartum ovarian vein
      thrombosis after vaginal delivery. METHODS: We reviewed medical records of
      patients with the prior diagnosis of septic pelvic thrombophlebitis, deep vein
      thrombosis, and pulmonary embolism associated with pregnancy. The study covered
      the 10-year period from July 1984 through August 1994 and included women
      hospitalized at E.H. Crump Women's Hospital, Regional Medical Center, University
      of Tennessee, Memphis, Tennessee. RESULTS: During the study period, there were
      76,858 deliveries: 13,109 cesareans and 63,749 vaginal deliveries. Eleven
      patients had documented postpartum ovarian vein thrombosis after vaginal
      delivery. Ten patients were readmitted an average of 7.6 days after delivery
      (range 3-17). The diagnosis was documented by computed tomography (CT) scan or
      ultrasound in ten women and laparotomy in one. Nine patients were readmitted with
      the presumptive diagnosis of endometritis, the other two with the presumptive
      diagnosis of pyelonephritis. Nine were treated initially with ampicillin,
      gentamicin, and clindamycin. Heparin therapy was added when failure of clinical
      response was noted. No patient defervesced within 24 hours of beginning heparin
      therapy; only two patients defervesced within 48 hours, and the remaining
      patients became afebrile at an average of 6.8 days (range 4-18, median 5).
      CONCLUSION: The diagnosis of ovarian vein thrombosis should be considered early
      in the care of patients readmitted with a diagnosis of endometritis after vaginal
      delivery. If prompt defervescence does not occur with aggressive intravenous
      antibiotic therapy, a CT scan should be obtained in a timely manner for prompt
      diagnosis and therapy. Our findings do not support the time-honored rule that
      septic pelvic thrombophlebitis and ovarian vein thrombosis respond within 24-48
      hours to therapeutic anticoagulation with heparin.

PMID- 7724113
TI  - Blinded manuscript review: an idea whose time has come?

PMID- 7724114
TI  - Residents' attitudes to training in ethics in Canadian obstetrics and gynecology
      programs.
AB  - OBJECTIVE: To determine residents' attitudes toward their current training in
      ethics, including their preferred learning format, time commitment, and the
      influences of training and personal background on their views and decision-making
      process. METHOD: All 203 residents from English-speaking Canadian obstetrics and
      gynecology programs were mailed an 18-question, numerical-response questionnaire
      in prestamped return envelopes. One hundred thirty-one residents (64.5%)
      responded (81 to the first mailing and 50 to the second). RESULTS: The number of
      hours in the residency program devoted to ethical issues correlated positively
      with the residents' perception of the residency program in shaping their ethical
      views (P = .015, r = 0.22). Of the respondents, 44.7% preferred case
      presentations as their learning format and 30.7% ranked seminars as their first
      choice. Informal discussions and rounds were less popular, and lectures were
      considered least appropriate by 69.3%. When asked what most influenced the
      residents' ethical decision-making process, 34.2% indicated family views, 17.1%
      undergraduate teaching, 15.4% religious background, 12.8% views of consulting
      staff, 11.1% residency training, and 9.4% peer attitudes. Sixty-eight percent of
      residents felt that their training in ethics during their residency program
      should be increased; this may reflect response bias. A position of conscience
      conflict during residency training was reported by 28.9% of residents.
      CONCLUSION: Findings from this survey support the benefit of more discussion of
      ethical issues during residency programs, particularly with the use of case
      presentations.

PMID- 7724115
TI  - Sexuality, reproduction, and contraception among residents in obstetrics and
      gynecology.
AB  - OBJECTIVE: To investigate the contraceptive practices and attitudes of residents
      in obstetrics and gynecology, both personally and professionally. METHODS: We
      conducted a national survey of obstetrics and gynecology residents. RESULTS: One
      thousand ninety-one questionnaires (29% of those mailed) were returned,
      representing 3761 residents in 218 of the 275 programs surveyed. Less than 2% of
      this population wishing to avoid conception failed to use contraception. The oral
      contraceptive (OC) pill, the most common current method of contraception (59%),
      was significantly more prevalent among female residents than among female
      partners of male residents (P < .001). Condom use was more prevalent among male
      residents than among partners of female residents (P = .005). When controlled for
      age, parity, and marital status, and using log linear analysis, gender had a
      statistically significant impact on the use of several contraceptive methods.
      Female residents were five times more likely than a comparably educated,
      nonphysician group of women to use OCs. Twenty-six percent of respondents stated
      that they would not use the intrauterine device (IUD) personally, but might
      recommend it to their patients. CONCLUSIONS: Residents in obstetrics and
      gynecology demonstrate a high prevalence of contraceptive use. Controlling for
      demographic variables, we found that male and female residents have different
      attitudes on contraceptive use. Residents believe that OC use is safe and
      reliable for themselves and their patients, but demonstrate doubt about their own
      use of an IUD.

PMID- 7724116
TI  - Net effect of oral contraceptive use on the risk of cancer in women in the United
      States.
AB  - OBJECTIVE: To estimate by meta-analysis the risk of developing cancer of the
      breast, uterine cervix, endometrium, ovary, and liver from age 20-54 years in the
      United States in women using oral contraceptives (OCs) for 4, 8, or 12 years.
      DATA SOURCES: Using pairs of terms (such as oral contraception and breast
      neoplasms), I searched for English-language literature on OC use and cancer
      published since 1980 and cited through July 1994 in the MEDLINE data base.
      METHODS OF STUDY SELECTION: I analyzed all epidemiologic studies reporting
      estimates of relative risk (RR) by duration and recency of OC use (79 independent
      studies in total). DATA EXTRACTION AND SYNTHESIS: Reported duration-specific and
      recency-specific estimates of RR, with the corresponding numbers of cases and
      controls or person-time at risk for cohort studies, were abstracted from each
      article. Relative risk of cancer as a function of both duration and recency of OC
      use was then estimated by weighted regression and applied, using life-table
      methods, to United States population-based data on age-specific mortality and
      cancer incidence. CONCLUSIONS: For every 100,000 women in the United States who
      never use OCs, the number developing cancer from age 20-54 years is estimated to
      be 2782 (breast), 425 (cervix), 438 (endometrium), 369 (ovary), and 20 (liver).
      For women using OCs for 8 years, the estimated number of additional or fewer
      cases per 100,000 users is +151 (breast), +125 (cervix), -197 (endometrium), -193
      (ovary), and +41 (liver). Therefore, from a population perspective, there are
      only small cancer-related risks and benefits associated with OC use and, on
      balance, the net effect is negligible.

PMID- 7724117
TI  - Fetal acidemia associated with regional anesthesia for elective cesarean
      delivery.

PMID- 7724118
TI  - Fetal acidemia associated with regional anesthesia for elective cesarean
      delivery.

PMID- 7724119
TI  - Histiocytosis X and pregnancy.
AB  - BACKGROUND: Histiocytosis X, a clinically heterogeneous infiltrating disorder, is
      rarely associated with pregnancy. Diabetes insipidus is a common manifestation of
      histiocytosis X. CASE: A 27-year-old pregnant woman was diagnosed with
      histiocytosis X by biopsy. At 31 weeks' gestation, she developed diabetes
      insipidus and required treatment with intranasal 8-D-arginine vasopressin. A
      hypothalamic mass was noted on magnetic resonance imaging. She delivered a 363-g
      male at term by cesarean. Two months postpartum, after a motor vehicle accident,
      she developed a T6 sensory and motor deficit. An intramedullary spinal cord mass
      was diagnosed and surgically removed. She was treated postoperatively with
      radiation therapy to the spine and hypothalamus. Despite systemic chemotherapy,
      the disease progressed, and the patient died 18 months after delivery.
      CONCLUSION: Pregnancy in patients suffering from histiocytosis X is rare. When
      pregnancy and histiocytosis X do coincide, diabetes insipidus may appear or
      worsen. Treatment with intranasal 8-D-arginine vasopressin does not pose risks
      for the fetus or for premature labor.

PMID- 7724120
TI  - Hypoglycemia in pregnancy secondary to a non-islet cell tumor of the pleura and
      ectopic insulin-like growth factor II hormone production.
AB  - BACKGROUND: In nondiabetic women, pregnancy alone rarely causes clinical
      hypoglycemia. Non-islet cell tumors have recently been shown to be associated
      with the production of insulin-like growth factor II (IGF-II) and a
      paraneoplastic syndrome resulting in hypoglycemia. A case report and review of
      pathophysiologic mechanisms involved is presented. CASE: A 38-year-old
      multigravida presented suffering from clinical and biochemical hypoglycemia,
      which was found to be secondary to a mesothelioma of the pleura and ectopic IGF
      II production. Tumor resection was performed during the 13th gestational week.
      The mother became euglycemic immediately after the surgery and remained
      asymptomatic. Clinical indicators of pregnancy and an ultrasound scan after the
      surgery were consistent with a normal viable fetus. CONCLUSION: Symptomatic
      hypoglycemia and other medical conditions occurring during pregnancy require
      immediate diagnosis and treatment. In addition to the more common causes,
      documented cases of medical conditions due to paraneoplastic syndromes of ectopic
      hormone production during pregnancy have been described. This case establishes
      the non-islet cell tumor with IGF-II-induced hypoglycemia as another such
      syndrome to be considered when evaluating hypoglycemia in pregnancy.

PMID- 7724121
TI  - Cutaneous mastocytosis complicating pregnancy.
AB  - BACKGROUND: Telangiectasia macularis eruptiva perstans, a rare form of cutaneous
      mastocytosis associated with elevated histamine excretion, has not previously
      been reported to complicate pregnancy. CASE: A woman presented in the late second
      trimester with an anaphylactoid reaction, rash, uterine contractions, and vaginal
      bleeding. Skin biopsy revealed perivascular mast-cell infiltration. Her urinary
      histamine excretion was markedly elevated. She was treated successfully with
      tocolytics and antihistamines. CONCLUSION: Elevated histamine excretion in biopsy
      proven cutaneous mastocytosis may be associated with preterm labor.

PMID- 7724122
TI  - Polyhydramnios and hypercalcemia associated with congenital mesoblastic nephroma:
      case report and a new appraisal.
AB  - BACKGROUND: Polyhydramnios and hypercalcemia are known complications of
      congenital mesoblastic nephroma. Hypercalcemia has been shown to cause polyuria.
      Polyuria is believed to be the probable cause for the polyhydramnios, but the
      exact mechanism remains unknown. To our knowledge, this is the first reported
      case of a relationship between hypercalcemia and polyhydramnios. CASE: A 26-year
      old primigravida was diagnosed with congenital mesoblastic nephroma and
      polyhydramnios at 36 weeks' gestation. Neonatal hypercalcemia was detected
      immediately after delivery at 40 weeks' gestation. After removal of the nephroma,
      the calcium level normalized. CONCLUSION: Hypercalcemia may be the mechanism
      underlying polyhydramnios in cases of congenital mesoblastic nephroma. Calcium
      levels should be monitored after delivery, and prompt surgical removal of the
      tumor should be performed.

PMID- 7724123
TI  - Coarctation of the abdominal aorta in pregnancy: diagnosis by magnetic resonance
      imaging.
AB  - BACKGROUND: Coarctation of the aorta is rare, affecting one per 2000-3000 women.
      Abdominal coarctation is more commonly identified in women than in men, but only
      two cases have been reported in pregnancy. CASE: A 26-year-old woman was
      diagnosed with hypertension at 15 years of age. Her blood pressure was controlled
      adequately with beta-blockers. During her pregnancy, she was found to have
      coarctation of the abdominal aorta by magnetic resonance imaging. CONCLUSION:
      Magnetic resonance imaging is a safe, reliable means by which to confirm
      clinically suspected coarctation of the aorta during pregnancy.

PMID- 7724124
TI  - Liver transplant after massive spontaneous hepatic rupture in pregnancy
      complicated by preeclampsia.
AB  - BACKGROUND: Spontaneous hepatic rupture associated with preeclampsia is a rare
      but life-threatening situation. Several different surgical treatments have been
      described, depending on the severity of the rupture. Liver transplantation has
      become the mainstay for patients with end-stage liver disease. Transplantation in
      the setting of liver trauma or massive parenchymal disruption is not well
      defined. To our knowledge, this treatment has not been reported for spontaneous
      hepatic rupture in pregnancy. CASE: Massive, spontaneous hepatic rupture occurred
      in a patient at 36 weeks' gestation as a result of severe preeclampsia.
      Conventional surgical therapies were unsuccessful in controlling the massive
      hemorrhage. As a life-saving measure, the patient underwent total hepatectomy
      with the creation of an end-to-side portcaval shunt, thereby rendering the
      patient anhepatic. The patient was listed as urgently needing a liver for
      transplantation through the United Network for Organ Sharing. A suitable donor
      liver was located approximately 8 hours after the emergency hepatectomy. The
      patient underwent orthotopic liver transplantation after being maintained in an
      anhepatic state for almost 13 hours. The patient was discharged on postoperative
      day 41, suffering only from some ischemic lower extremity neuropathy secondary to
      hypovolemic hypotension occurring during the hepatectomy procedure. CONCLUSION:
      In the reported case, spontaneous hepatic rupture resulted in a massive
      hemorrhage that could not be controlled by previously reported techniques and
      required total hepatectomy followed by liver transplantation.

PMID- 7724125
TI  - Endovascular stent placement and magnetic resonance angiography for management of
      hypertension and renal artery occlusion during pregnancy.
AB  - BACKGROUND: Severe renovascular hypertension carries serious maternal and fetal
      risk. In patients failing medical therapy, therapeutic options include surgical
      revascularization, nephrectomy, and percutaneous angioplasty. CASE: A pregnant
      woman with long-standing hypertension developed accelerated hypertension despite
      multiple drug therapy. Magnetic resonance angiography diagnosed an atrophic
      kidney with a critical proximal right renal artery lesion. At 17 weeks'
      gestation, this renal artery occlusion was treated with percutaneous angioplasty
      and endovascular stent placement; hypertension has improved markedly, allowing
      discontinuation and tapering of her antihypertensive medications. Total fetal
      radiation dose was 0.002 Gy. CONCLUSION: Magnetic resonance angiography is a
      promising, noninvasive diagnostic method of evaluating renovascular hypertension
      during pregnancy. Transluminal angioplasty and endovascular stent placement can
      be performed safely and effectively with nominal fetal radiation exposure.

PMID- 7724126
TI  - Pregnancy in a woman with class H diabetes mellitus and previous coronary artery
      bypass graft: a case report and review of the literature.
AB  - BACKGROUND: Maternal and fetal mortality have been reported to be high in
      pregnant women with diabetes mellitus and ischemic heart disease. Review of the
      literature identified only two cases of pregnancy after coronary artery bypass
      surgery in diabetic patients. Because of limited case experience, there are no
      clear recommendations for counseling and managing such patients. CASE: We managed
      a pregnancy complicated by class H diabetes mellitus in which the patient had an
      earlier need for four-vessel coronary artery bypass surgery. The application of
      contemporary techniques for diabetic and cardiac management led to successful
      maternal and perinatal outcomes at 36 weeks' gestation. CONCLUSION: Preconception
      coronary artery bypass surgery, along with contemporary medical and obstetric
      management, may lead to improvement in the outcome of pregnancies complicated by
      class H diabetes.

PMID- 7724128
TI  - Kasabach-Merritt coagulopathy complicating Klippel-Trenaunay-Weber syndrome in
      pregnancy.
AB  - BACKGROUND: Klippel-Trenaunay-Weber syndrome is a sporadic genetic syndrome
      characterized by localized hemangiomas, venous varicosities, and asymmetric
      osseous hypertrophy of the ipsilateral extremities. Most commonly seen in
      association with hemangiomas, Kasabach-Merritt syndrome is defined by the
      presence of thrombocytopenia and a consumptive coagulopathy. CASE: A 22-year-old
      primigravida with a prior diagnosis of Klippel-Trenaunay-Weber syndrome presented
      for genetic counseling and delivery management at 37 weeks' gestation. Large
      varicosities of the vulva required cesarean delivery. Multiple hemangiomas in the
      right lower quadrant of the abdomen necessitated the use of a left paramedian
      cutaneous incision. The patient subsequently developed Kasabach-Merritt syndrome
      and required the transfusion of blood products as well as heparin and
      aminocaproic acid therapy for her postoperative management. CONCLUSION: Klippel
      Trenaunay-Weber syndrome in pregnancy is rare. The potential for a refractory
      coagulopathy presenting as Kasabach-Merritt syndrome should be considered in any
      patient who presents with extensive hemangiomas.

PMID- 7724127
TI  - Pregnancy complicated by von Hippel-Lindau disease.
AB  - BACKGROUND: Von Hippel-Lindau disease is an autosomal-dominant genetic disorder
      with variable penetrance characterized by multiorgan hemangioblastomas and a
      predisposition to carcinoma. CASE: A 23-year-old pregnant woman at 35 weeks'
      gestation, with a family history of von Hippel-Lindau disease, presented with
      paraplegia caused by an acute intramedullary hemorrhage from a spinal hemangioma
      at the thoracic (T) 4-5 level. An unruptured hemangioblastoma was noted at the T7
      8 level. A T3-6 laminectomy resulted in the improvement of symptoms. The
      postoperative period was complicated by autonomic dysreflexia and preterm labor.
      The woman was delivered by cesarean under epidural anesthesia. CONCLUSION:
      Pregnant patients with von Hippel-Lindau disease present problems related to
      hemangioblastomas of the central nervous system. Imaging studies of the central
      nervous system are mandatory for prompt recognition and treatment of
      complications related to intramedullary hemorrhage. If spinal hemangioblastomas
      are identified, cesarean delivery may be the most sensible choice.

PMID- 7724129
TI  - Sacroiliitis associated with pyelonephritis in pregnancy.
AB  - BACKGROUND: Sacroiliitis is a rare infection and an unusual cause of back pain
      during pregnancy. Because pregnancy and infections commonly associated with
      pregnancy are risk factors, this diagnosis should be considered in the gravida
      with sacroiliac pain. CASE: A 17-year-old woman at 24 weeks' gestation, with a
      history of illicit drug use, presented to a local emergency room with back and
      buttock pain. Bacteriuria and pyuria were diagnosed, and cefazolin was initiated.
      Blood cultures grew Staphylococcus aureus and Escherichia coli. Despite prolonged
      antibiotic therapy for possible endocarditis, she had persistent debilitating
      lower back and buttock pain. Radiographic studies detected sacroiliitis, and
      broadened antibiotic therapy effected cure. CONCLUSION: When sacroiliitis is
      suspected, diagnostic imaging with either computed axial tomography, or,
      preferably, magnetic resonance imaging may be helpful. Antibiotic therapy should
      be tailored to the specific organism involved and continued for 3-6 weeks.

PMID- 7724130
TI  - A thrombogenic uterine pack for postpartum hemorrhage.
AB  - BACKGROUND: A low-lying placenta or placenta previa is frequently associated with
      postpartum hemorrhage from a low implantation site. We describe the successful
      use of a thrombin-soaked uterine pack for this condition. CASE: A 30-year-old
      woman, gravida 3, para 0-0-2-0, had placenta previa diagnosed by ultrasound at 26
      weeks' gestation. A repeat examination at 35 weeks demonstrated a low-lying
      placenta. The patient had an uncomplicated intrapartum course and was delivered
      by vacuum extraction, but excessive vaginal bleeding was noted 3 hours after
      spontaneous delivery of the placenta. Oxytocin, prostaglandin, and uterine
      curettage failed to control the hemorrhage. In an attempt to avoid laparotomy, we
      placed a thrombin-soaked uterine pack over the bleeding site. There was minimal
      vaginal bleeding during the following 8 hours, so the pack was removed. The
      patient had no further complications and was released 3 days after delivery.
      CONCLUSION: A thrombin-soaked uterine pack may successfully control lower uterine
      segment bleeding following delivery of a patient with a low-lying placenta. This
      technique offers the obstetrician another treatment option in selected cases of
      postpartum hemorrhage.

PMID- 7724131
TI  - Leuprolide acetate in the management of cesarean scar endometriosis.
AB  - BACKGROUND: Progestin or estrogen-progestin combination therapy has not proven
      useful in the treatment of endometriosis of the abdominal scar after cesarean
      delivery. We report our experience in managing this condition with a gonadotropin
      agonist. CASE: A 22-year-old black woman with a history of two previous cesareans
      developed endometriosis of the abdominal scar. The extent of the lesion was
      estimated by computed tomographic (CT) scan, and a 6-month preoperative course of
      leuprolide acetate was administered. The patient exhibited prompt symptomatic
      response to the gonadotropin agonist, but the physical examination and CT scan
      findings were unchanged. Pathologic examination after surgical removal of the
      lesion confirmed the clinical diagnosis. CONCLUSION: Leuprolide acetate
      administered to a patient with cesarean scar endometriosis was associated with an
      improvement in symptoms, but there was no change in lesion size.

PMID- 7724132
TI  - Postpartum thrombotic thrombocytopenic purpura complicated by Budd-Chiari
      syndrome.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura is an infrequent but devastating
      complication of pregnancy, often difficult to differentiate from severe
      preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low
      platelets (HELLP). To our knowledge, the combination of thrombotic
      thrombocytopenic purpura and hepatic vein thrombosis has not been reported
      previously in pregnancy. CASE: A 33-year-old woman, a multigravida, was delivered
      at 36 weeks' gestation because of pregnancy-induced hypertension and HELLP
      syndrome. Postpartum, the patient became obtunded, disoriented, and anuric. Her
      laboratory values revealed a Coombs-negative, microangiopathic hemolytic anemia,
      modestly abnormal coagulation studies, and thrombocytopenia. She also had
      elevated liver enzymes, lactate dehydrogenase, and creatinine. The largest plasma
      von Willebrand factor multimeric forms were relatively decreased in her
      ethylenediaminetetra-acetic acid-platelet-poor plasma. A diagnosis of thrombotic
      thrombocytopenic purpura was made. The patient received plasma exchange,
      hemodialysis, blood transfusion, and glucocorticoids. She responded to therapy,
      but was later noted to have increasing hepatosplenomegaly, rising levels of
      bilirubin, and elevated alkaline phosphatase. A Doppler study and magnetic
      resonance imaging demonstrated the absence of flow in the middle and left hepatic
      veins, secondary to thrombosis (Budd-Chiari syndrome). She was maintained on
      warfarin therapy and was discharged on postpartum day 50. CONCLUSION: The early
      recognition of thrombotic thrombocytopenic purpura is crucial for the initiation
      of appropriate treatment as soon as possible. The avoidance of platelet
      transfusion and early plasma-exchange therapy may be lifesaving.

PMID- 7724133
TI  - Pregnancy outcome when both members of a couple have balanced translocations.
AB  - BACKGROUND: Couples in which one partner is the carrier of a balanced
      translocation have increased risks of infertility, recurrent abortion, and
      delivery of chromosomally abnormal offspring. Pregnancies in which both partners
      carry balanced translocations are uncommon; therefore, only limited information
      regarding risk figures is available. We present a couple in which both members
      had a balanced translocation and discuss their pregnancy outcomes. CASE: A couple
      had three first-trimester spontaneous abortions at 12, 10, and 8 weeks'
      gestation, respectively. Both partners were found to be carriers of balanced
      autosomal translocations. The mother had a Robertsonian translocation with the
      karyotype 45,XX,t(13q14q). The father had a reciprocal translocation with a
      46,XY,t(1;4)(q32;q25) karyotype. There was no information regarding the karyotype
      of the patient's first-born child with a previous partner. The patient's first
      born child with her current partner carried a double balanced translocation
      karyotype of 45,XX,t(13;14)t(1;4). Their second and third children both had a
      45,XX,t(13q14q) karyotype. CONCLUSION: Couples in which both members have a
      balanced translocation are at increased risk for adverse pregnancy and fetal
      outcomes, but precise information regarding risk estimates for this rare
      circumstance is limited. Genetic counseling of such couples therefore presents a
      unique challenge.

PMID- 7724134
TI  - Prenatal detection of preaxial upper limb reduction in trisomy 18.
AB  - BACKGROUND: Abnormalities of the upper and lower extremities, such as club feet,
      rocker-bottom feet, and abnormal hand posturing, are frequently detected
      prenatally in trisomy 18 fetuses. Aplasia of the radius, usually associated with
      the absence or hypoplasia of the first metacarpal and thumb, is the most
      prevalent reduction malformation in trisomy 18 infants. Because this anomaly is
      easily missed during prenatal ultrasonography, the role of prenatal detection of
      this particular preaxial upper limb reduction has not been emphasized. CASES:
      Three cases of trisomy 18 in which preaxial upper limb reduction (radial aplasia)
      was identified prenatally by ultrasound are reported. Although in all cases there
      were additional ultrasonographic findings suggestive of trisomy 18, the prenatal
      detection of preaxial upper limb reduction facilitated the diagnosis. CONCLUSION:
      Ultrasonographic examination of fetal forearms for the detection of preaxial
      upper limb reduction should be a routine part of the prenatal evaluation of
      fetuses in whom trisomy 18 is suspected.

PMID- 7724135
TI  - Prenatal diagnosis and therapy for a fetal hepatic vascular malformation.
AB  - BACKGROUND: Congenital hepatic arteriovenous malformations complicated by high
      output heart failure and hematologic derangements are associated with up to 90%
      mortality. Prenatal diagnosis alerts the pediatrician to the need for early
      neonatal intervention. CASE: A fetal hepatic arteriovenous malformation with
      associated high-output cardiac failure was diagnosed at 29 weeks' gestation using
      real-time and color flow Doppler sonography. Hydrocortisone injected directly
      into the umbilical vein and the amniotic sac resulted in appreciable improvement
      in hemodynamic and hematologic indices. The pregnancy ended in a preterm delivery
      at 31 weeks with no evidence of heart failure at birth. CONCLUSION: The
      compromised preterm fetus with a hepatic arteriovenous malformation can be
      treated in utero, avoiding early emergency delivery.

PMID- 7724136
TI  - Prenatal diagnosis and management of massive bilateral axillary cystic
      lymphangioma.
AB  - BACKGROUND: Fetal lymphangiomas can occur in many different anatomic locations,
      including the most commonly seen nuchal cystic hygroma. CASE: A fetus at 18
      weeks' gestation was found to have a massive right axillary hygroma. The fetal
      karyotype was normal. Serial ultrasound examinations indicated progressive
      enlargement, but no hydrops. At 32 weeks' gestation, a left axillary hygroma was
      also diagnosed. The patient underwent cesarean delivery. CONCLUSION: Prenatal
      diagnosis of nuchal cystic hygromas has a high association with karyotypic
      abnormalities, hydrops, and fetal demise; however, this association may not apply
      to cystic lymphangiomas at other locations.

PMID- 7724137
TI  - Prenatal diagnosis of congenital imperforate hymen.
AB  - BACKGROUND: Congenital imperforate hymen is an external urogenital anomaly that
      has a small differential diagnosis. With careful antenatal sonographic evaluation
      of the female perineum, identification of a thin protruding membrane consistent
      with imperforate hymen can be made. CASE: We report a case in which an
      imperforate hymen was diagnosed in a fetus at 25 weeks' gestation. It appeared as
      a thin membrane that distended the vagina and spread the labia majora because of
      retained secretions. An associated renal abnormality was present, representing
      either a right multicystic dysplastic kidney or cystic dysplasia. CONCLUSION:
      Imperforate hymen and hydrocolpos can be diagnosed as early as the second
      trimester. Because of the additional renal anomaly in this case, it is suggested
      that the presence of prenatally diagnosed imperforate hymen warrants a careful
      survey of the remaining fetal anatomy to rule out associated abnormalities. The
      possibility of a familial occurrence should be considered, and the appropriate
      history should be obtained.

PMID- 7724138
TI  - Prenatal diagnosis of fetal disseminated intravascular coagulation associated
      with umbilical cord arteriovenous malformation.
AB  - BACKGROUND: Congenital disseminated intravascular coagulation (DIC) has been
      reported in a variety of clinical settings, but to our knowledge, it has never
      been documented before birth. We describe prenatal identification of an umbilical
      cord vascular tumor and echogenic foci in the fetal liver leading to the
      diagnosis of fetal DIC by funipuncture. CASE: A large vascular tumor of the
      umbilical cord was identified using prenatal sonography. At 31 weeks' gestation,
      echogenic areas, which were thought to represent infarcts or thrombi, were seen
      in the liver. When funipuncture revealed florid fetal DIC, delivery was
      accomplished by cesarean to prevent intracranial bleeding. Pathologic examination
      of the umbilical cord tumor showed it to be a large arteriovenous malformation.
      CONCLUSION: Arteriovenous malformations may cause fetal coagulopathy. This case
      illustrates that funipuncture may be used to diagnose this condition and that
      timely cesarean delivery may contribute to a favorable outcome.

PMID- 7724139
TI  - Aorto-pulmonary calcification: an unusual manifestation of idiopathic
      calcification of infancy evident antenatally.
AB  - BACKGROUND: Idiopathic arterial calcification of infancy represents a clinical
      spectrum involving calcification of large and medium-sized blood vessels with an
      unknown etiology. Its complications include severe systemic hypertension and
      cardiomyopathy. CASE: A twin infant with a variant of idiopathic arterial
      calcification was diagnosed antenatally by the detection of hyperechogenicity of
      the proximal aorta and central pulmonary vessels. The calcification was
      apparently isolated to these vessels and was associated with polyhydramnios and
      hypertrophic cardiomyopathy. CONCLUSION: Because antenatal diagnosis is possible,
      we suggest that there should be a high index of suspicion for idiopathic arterial
      calcification when there is sonographic hyperechogenicity of vessel walls,
      evidence of polyhydramnios, cardiomyopathy, or a family history of idiopathic
      arterial calcification.

PMID- 7724140
TI  - Porencephaly secondary to fetal trauma during amniocentesis.
AB  - BACKGROUND: There has been one reported case of porencephaly diagnosed
      postnatally as a result of amniocentesis. We report the first antenatal diagnosis
      of porencephaly, which apparently resulted from penetration of the fetal skull
      during amniocentesis. CASE: A 37-year-old woman had genetic amniocentesis at 16
      weeks' gestation. The fetal skull was penetrated during the unguided procedure.
      Porencephaly discovered at 28 weeks' gestation was confirmed by imaging studies
      in the neonatal period. CONCLUSION: Inadvertent fetal skull penetration appeared
      to result from amniocentesis unguided by continuous ultrasound.

PMID- 7724141
TI  - The relation between pulmonary hypoplasia and amniotic fluid volume: lessons
      learned from discordant urinary tract anomalies in monoamniotic twins.
AB  - BACKGROUND: Adequate amniotic fluid (AF) volume is one of several factors felt to
      be essential for normal lung development. Renal agenesis and urinary tract
      obstruction usually result in oligohydramnios and pulmonary hypoplasia. CASE: Two
      sets of monoamiotic twins with discordant urinary tract anomalies were seen. One
      twin in each set had anomalies that in a singleton or diamiotic pregnancy would
      likely have resulted in fetal pulmonary hypoplasia and subsequent death. However,
      neither of these infants had pulmonary hypoplasia. One infant is unique in being
      the first case reported of normal pulmonary function and survival despite the
      anomaly. CONCLUSION: Adequate AF provided by a monoamniotic twin environment may
      prevent pulmonary hypoplasia, which usually results from oligohydramnios due to
      certain fetal urinary tract anomalies.

PMID- 7724142
TI  - Umbilical artery occlusion and fetoplacental thromboembolism.
AB  - BACKGROUND: To our knowledge, fetoplacental thromboembolism has been described
      only in autopsy specimens. We report the antepartum diagnosis of an umbilical
      artery occlusion and neonatal diagnosis of an aortic thrombus and placental
      emboli. CASE: A gravida at 31 weeks' gestation was referred for evaluation of
      decreased fetal movement and an enlarged fetal bladder. A two-vessel umbilical
      cord with a collapsed, echogenic third vessel was noted, whereas views of a
      normal three-vessel cord were available from an examination 5 weeks earlier. A
      positive oxytocin contraction test prompted delivery. Neonatal color flow Doppler
      imaging demonstrated an aortic thrombus below the renal arteries and above the
      bifurcation. Gross and microscopic study of the placenta demonstrated necrosis of
      the collapsed umbilical artery and numerous placental emboli. The aortic thrombus
      resolved gradually, and the infant went home on the 39th day of life. CONCLUSION:
      Umbilical artery occlusion can be diagnosed ultrasonographically and may be a
      sign of fetoplacental thromboembolism. Assessment of fetal oxygenation status by
      biophysical profile or contraction stress test may be helpful in the evaluation
      of umbilical artery occlusion.

PMID- 7724143
TI  - Direct fetal administration of adenosine for the termination of incessant
      supraventricular tachycardia.
AB  - BACKGROUND: Adenosine terminates supraventricular reentry tachycardia safely and
      effectively in the pediatric age group. CASE: The recurrence of pretreated
      incessant tachycardia led to severe hydrops in a 28-week-old fetus. The
      tachycardia was terminated instantly with direct fetal administration of
      adenosine via the umbilical vein. Normal heart rate and rhythm were then
      preserved temporarily with digoxin and flecainide. CONCLUSION: Direct fetal
      adenosine administration might be helpful in the treatment of fetal reentry
      tachycardias if the sinus rhythm achieved quickly can be preserved by long-acting
      antiarrhythmic drugs. Such a combined therapeutic approach might be especially
      advantageous in hydropic fetuses.

PMID- 7724144
TI  - Constriction of the fetal ductus arteriosus during prenatal betamethasone
      therapy.
AB  - BACKGROUND: Constriction of the fetal ductus arteriosus occurs with maternal
      indomethacin treatment and has been suggested with corticosteroid therapy as
      well. CASE: Fetal ductal constriction was diagnosed by Doppler echocardiography
      at 29 weeks' gestation after a third and fourth course of betamethasone was
      administered to a pregnant woman with placenta previa. Doppler echocardiography
      showed a patent ductus arteriosus 3 days after the treatment. CONCLUSION: The
      risk-benefit ratio of betamethasone should be assessed by large-scale studies
      when repeated courses or chronic maternal administration of betamethasone are
      required.

PMID- 7724146
TI  - Expectant management of a hypothalamic mass: a case report.
AB  - BACKGROUND: Although hypothalamic masses are usually benign, they may infiltrate
      hypothalamic-pituitary structures, resulting in multiple endocrinopathies, optic
      nerve damage, increased intracranial pressure, and death. Controversy exists
      regarding proper management. CASE: A young woman with a hypothalamic mass
      suggestive of craniopharyngioma presented with pubertal delay and hypothalamic
      amenorrhea without evidence of progression over 4 years. She was given sex
      steroid replacement and observed, thereby avoiding surgery or radiotherapy.
      CONCLUSION: Large hypothalamic masses may present with minimal signs and symptoms
      that are not life threatening. Without more serious symptoms, these can be
      managed expectantly to avoid the risks of panhypopituitarism, diabetes insipidus,
      vision loss, and cerebrovascular accidents resulting from any therapy.

PMID- 7724145
TI  - Intrauterine therapy for homozygous alpha-thalassemia.
AB  - BACKGROUND: Alpha-thalassemia is one of the most common genetic disorders in the
      world and is becoming more common in the United States with the increase in
      immigration of susceptible populations. This disease has been stated previously
      to be incompatible with extrauterine life. CASE: A Filipino woman with a prior
      loss due to hemoglobin Bart's underwent prenatal diagnosis that confirmed
      recurrence in the index pregnancy. Intravascular intrauterine exchange
      transfusions maintained appropriate fetal growth. A cesarean delivery yielded a
      2190-g male infant with minor malformations. The postnatal course was
      characterized by mild respiratory insufficiency. Postnatal chronic transfusion
      therapy is underway pending consideration for bone marrow transplantation.
      CONCLUSION: Antenatal diagnosis and therapy of homozygous alpha-thalassemia can
      prevent the prenatal consequences of hydrops and fetal death. New technologies
      such as stem cell transplantation may help to avert both prenatal and postnatal
      consequences.

PMID- 7724147
TI  - Combined abdominal-perineal sonography to assist in diagnosis of transverse
      vaginal septum.
AB  - BACKGROUND: Transperineal sonography has been used to detect incompetent
      cervices, placenta previa, cervical pregnancy, and vaginal and cervical atresia.
      CASE: Transperineal sonography was used to investigate primary amenorrhea in a 14
      year-old girl. A mid-transverse septum was found and confirmed surgically.
      CONCLUSION: Transperineal or translabial sonography assisted in the
      differentiation of primary amenorrhea, when adequate vaginal access was
      prohibited.

PMID- 7724148
TI  - Ultrasound and hookwire needle placement for localization of a hydrocele of the
      canal of Nuck.
AB  - BACKGROUND: Hydrocele of the canal of Nuck is a mobile mass entity that can be
      difficult to locate and excise. We report the use of ultrasound scan and a
      hookwire needle to localize and stabilize this mass, making its excision easier.
      CASE: A 24-year-old white female presented with a 6-month history of a painful
      vulvar mass associated with increased discomfort with prolonged standing.
      Thorough evaluation revealed a suspected hydrocele that was easily palpable in
      the standing position but not in the lithotomy position. Translabial
      ultrasonography and a hookwire needle were used to localize and stabilize the
      mobile vulvar mass, eliminating the need for extensive surgical exploration.
      CONCLUSION: Ultrasound scanning and needle localization is a useful technique to
      identify and stabilize a mobile mass, making its surgical excision possible
      without extensive exploration and trauma.

PMID- 7724149
TI  - Localization of "lost" Norplant capsules using compression film screen
      mammography.
AB  - BACKGROUND: The complications of Norplant removal relate primarily to the length
      of time and amount of dissection required for removal of the capsules.
      Complications include swelling and pain at the removal site and, at times,
      capsule fracture. The inability to locate one or more of the capsules is a rare
      complication. Recommended methods for locating the capsules include plain film
      radiography and ultrasound imaging. However, in circumstances where neither of
      these techniques succeeds, no specific recommendations exist to enhance
      visibility of the capsules. CASE: We used compression film screen mammographic
      techniques of the soft tissue at the site of insertion to locate a "lost"
      Norplant capsule after both plain films and ultrasound images failed to reveal
      the location of the capsule. CONCLUSION: Film screen mammographic techniques may
      help locate "lost" Norplant capsules that are not visualized with either plain
      film radiography or ultrasound imaging of the insertion site.

PMID- 7724150
TI  - Pelvic magnetic resonance imaging in the evaluation of uterine torsion.
AB  - BACKGROUND: Uterine torsion is defined as the rotation of more than 45 degrees
      around the long axis of the uterus. An uncommon but potentially fatal event,
      uterine torsion is rarely diagnosed until the time of surgery. With magnetic
      resonance imaging (MRI), however, an accurate diagnosis of uterine torsion may
      now be made preoperatively. CASE: We describe a patient with uterine torsion in
      whom the correct diagnosis was made prenatally with the use of MRI, by the
      demonstration of an X-shaped configuration of the upper vagina. CONCLUSION:
      Distinctive features suggestive of uterine torsion were demonstrated by MRI and
      enabled an accurate preoperative diagnosis. To our knowledge, this is the first
      reported case of uterine torsion diagnosed on MRI.

PMID- 7724151
TI  - Membranous dysmenorrhea: the forgotten entity.
AB  - BACKGROUND: Membranous dysmenorrhea involves the spontaneous slough of the
      endometrium in one cylindrical or membranous piece that retains the shape of the
      uterine cavity. Because this entity is rarely mentioned in the medical
      literature, the purpose of this report is to describe two such cases. CASES: An
      18-year-old nullipara with regular menstrual cycles presented with membranous
      dysmenorrhea after taking the contraceptive Gynera (Gestodene 0.075 mg, ethinyl
      estradiol 0.030 mg). Symptoms disappeared when the medication was discontinued.
      The second patient, a 26-year-old woman, gravida 1, para 1, was on a 10-day
      monthly regimen of Provera (medroxyprogesterone acetate) 2.5 mg/day for
      dysfunctional uterine bleeding. When the Provera dose was increased to 10 mg/day,
      the symptoms disappeared. CONCLUSION: Membranous dysmenorrhea is "a disease of
      theories" with various recommended medications. When this condition is caused by
      iatrogenic treatment, the best approach is to discontinue the offending drug or
      change its dosage.

PMID- 7724152
TI  - Pyometra after endometrial resection and ablation.
AB  - BACKGROUND: Hysteroscopic endometrial ablation is increasingly accepted as a safe
      means of controlling excessive uterine bleeding. CASE: A 47-year-old woman
      underwent endometrial resection and ablation for menorrhagia and subsequently
      developed pyometra and bacteremia. Placement of an intrauterine drain and
      intravenous antibiotic therapy led to full recovery. CONCLUSION: Postoperative
      pyometra occurred after endometrial resection and ablation, a procedure reported
      to have few complications. To our knowledge, this has not been reported before.

PMID- 7724153
TI  - Pelvic Castleman disease mimicking an adnexal tumor.
AB  - BACKGROUND: Castleman disease, or giant lymph node hyperplasia, is a rare cause
      of lymph node enlargement. Only 11 cases with pelvic localization in women have
      been reported. CASE: A pelvic mass mimicking an adnexal tumor was detected on a
      routine examination in a 26-year-old woman. Surprisingly, the pelvic organs were
      found to be normal at laparotomy. Eight years later, the subject was examined for
      dyspareunia and secondary infertility that lasted 2 years. A pelvic mass,
      evidently the one encountered 8 years previously, was detected; it had enlarged
      only slightly in the intervening time. Surgical exploration of the retropubic
      space revealed a tumor-like mass attached to the periosteum of the left superior
      pubic arch. The mass was removed by simple resection. Histologic investigations
      confirmed a diagnosis of Castleman disease. Three months after the operation, the
      woman conceived without any further treatment. CONCLUSION: The possibility of
      Castleman disease should be considered when assessing a pelvic mass. The
      condition in the retropubic space in women has not been reported previously.

PMID- 7724154
TI  - Asherman syndrome caused by schistosomiasis.
AB  - BACKGROUND: Rare causes of Asherman syndrome include infections of the
      endometrium, such as tuberculosis and schistosomiasis. CASE: A 27-year-old Zulu
      woman, para 1, presented with secondary amenorrhea after an uncomplicated
      cesarean delivery. Hormone levels were in the normal ranges. Laparoscopy revealed
      some pelvic adhesions with patent fallopian tubes, and biopsy of the ovary showed
      schistosomiasis. Diagnostic D&C revealed a uterine cavity partially obliterated
      by adhesions. The patient was treated with praziquantel. CONCLUSION:
      Schistosomiasis should be considered as a possible cause of infertility and
      Asherman syndrome in those parts of the world where it is endemic.

PMID- 7724155
TI  - Recurrent transient superior vena cava-like syndrome possibly associated with
      megestrol acetate.
AB  - BACKGROUND: Superior vena cava syndrome is a rare, life-threatening clinical
      entity associated with occlusion of venous outflow from the head, neck, and upper
      extremities; this syndrome produces facial edema, cyanosis, dyspnea, and
      prominent neck veins, and is usually caused by intrathoracic neoplasms. CASE: In
      this unusual case, a patient receiving megestrol acetate for stage IV endometrial
      carcinoma developed recurrent transient superior vena cava-like syndrome in the
      absence of venous obstruction. CONCLUSION: Superior vena cava-like syndrome may
      occur with megestrol acetate. This unusual complication should be considered in
      patients receiving this medication who present with symptomatology similar to
      that of superior vena cava syndrome.

PMID- 7724156
TI  - Use of a long-acting GnRH agonist for benign cystic mesothelioma.
AB  - BACKGROUND: Benign cystic mesothelioma, a tumor characteristically found in women
      during the reproductive years, is rare after bilateral oophorectomy or menopause,
      suggesting hormonal sensitivity. CASE: We treated a 17-year-old woman with a
      rapidly increasing and symptomatic benign cystic mesothelioma with a long-acting
      GnRH agonist. A rapid and continued reduction in volume corresponded to the
      induction and maintenance of a hypoestrogenic state over a 6-month period.
      However, the subsequent addition of a combination of estrogen and progestin
      (known as add-back therapy) resulted in a gradual increase in cyst volume, which
      progressed after discontinuation of all therapy. Resumption of GnRH-analog
      therapy alone reduced cyst volume again, and the patient underwent surgical
      removal. CONCLUSION: Long-acting GnRH agonists may have a role in the
      conservative management of these rare neoplasms. The reduction in volume
      concomitant with a hypoestrogenic state and regrowth with addition of add-back
      therapy further suggest extreme sensitivity of this tumor to one or both
      hormones.

PMID- 7724157
TI  - A case of uterine cervical adenoid cystic carcinoma: immunohistochemical study
      for basement membrane material.
AB  - BACKGROUND: Adenoid cystic carcinoma is a rare neoplasm of the cervix. Only two
      reports of immunohistochemical studies for basement membrane material in adenoid
      cystic carcinoma of the cervix have been reported. CASE: An 80-year-old Japanese
      woman complained of atypical vaginal bleeding and underwent removal of a cervical
      polyp; the biopsy specimen revealed a solid variant of adenoid cystic carcinoma.
      The tumor was composed of nests and nodules of small carcinoma cells, and there
      were few characteristic cribriform patterns. Immunohistochemical findings for
      type IV collagen and laminin revealed intercellular cylinders composed of
      basement membrane material in the solid area without a cribriform pattern.
      CONCLUSION: The immunohistochemical finding of intercellular cylinders that
      reacted for type IV collagen was useful for the diagnosis of a solid variant of
      adenoid cystic carcinoma.

PMID- 7724158
TI  - Villoglandular adenocarcinoma of the cervix: a case report.
AB  - BACKGROUND: Villoglandular adenocarcinoma of the cervix is a rare neoplasm
      associated with a favorable outcome and has not been described as a complication
      of pregnancy. CASE: A gravida at 20 weeks' gestation was found to have a bulky
      stage-IB adenocarcinoma of the cervix. She was delivered at 32 weeks' gestation
      by cesarean, then a radical hysterectomy and pelvic and periaortic
      lymphadenectomies were performed. Pathology revealed a deeply invasive, grade 1
      villoglandular adenocarcinoma confined to the cervix. The patient remains free of
      disease at 14 months follow-up. CONCLUSION: Villoglandular adenocarcinoma of the
      cervix has a favorable prognosis and can be managed conservatively, even when
      complicated by pregnancy.

PMID- 7724159
TI  - Are your employees fit to drive?

PMID- 7724160
TI  - A smoker's own perspective of policy.

PMID- 7724161
TI  - The OH aspects of working from home.

PMID- 7724162
TI  - The twists and turns of environmental litigation.

PMID- 7724163
TI  - OSHA's TB rulemaking. OSHA is attempting to publish a standard for controlling TB
      exposure in the workplace--in record time.

PMID- 7724164
TI  - Does your audiometric monitoring program measure up?
AB  - All hearing conservation programs under CFR 1910.95 require audiometric
      monitoring. This article provides an overview of OSHA noncompliance citations
      related to audiometric monitoring and associated monetary penalties reported
      between January 1988 and June 1994. The data in this article reflect the degree
      of seriousness of different elements of noncompliance, because monetary
      penalties, at least empirically, are related to severity or importance of the
      element.

PMID- 7724165
TI  - Truckers prepare for alcohol "stupidity test". Final part of DOT regulations
      effective May 1995.

PMID- 7724166
TI  - High-tech surgery for workers. When you consider total costs of an injury,
      advanced surgical techniques may be a bargain.

PMID- 7724167
TI  - Posterior vitreous detachment as a risk factor for retinal detachment.

PMID- 7724168
TI  - Exposed hydroxyapatite implants.

PMID- 7724169
TI  - Clarification of earlier correspondence.

PMID- 7724170
TI  - Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients
      with acquired immune deficiency syndrome.
AB  - PURPOSE: The authors previously conducted a pilot, dose-escalating study which
      suggested that a 20-micrograms dose of intravitreal cidofovir (HPMPC) may be safe
      and effective in treating cytomegalovirus (CMV) retinitis in humans. The purpose
      of this series is to expand the authors' prior experience with the 20-micrograms
      dose of cidofovir as the sole treatment for CMV retinitis in patients with
      acquired immune deficiency syndrome. METHODS: The study design was an unmasked
      consecutive case series trial in a single-center institutional retina referral
      practice. Eligible patients with acquired immune deficiency syndrome had active
      CMV retinitis in at least one eye and no evidence of extraocular CMV disease.
      Patients received a 20-micrograms cidofovir trans pars plana injection and were
      treated with concomitant oral probenecid. Retreatments were performed for
      progression of retinitis as determined by serial fundus photographs judged
      independently by three observers. The primary outcome was time to retinitis
      progression determined by Kaplan-Meier analysis. Both globes of one patient who
      had unilateral retinitis were examined pathologically. RESULTS: There were 37
      cidofovir injections in 24 eyes of 17 patients. The median time to retinitis
      progression after the initial 24 injections was 55 days. The median time to
      retinitis progression after 8 repeat cidofovir injections was 63 days. There was
      a significant decrease in intraocular pressure from baseline to both 2 and 4
      weeks after injection. A mild to moderate iritis developed in five (20.8%) eyes
      that responded well to topical medications. Results of histopathologic
      examination of one treated globe did not show any significant toxic effects.
      CONCLUSIONS: This study demonstrates that prolonged arrest of the progression of
      CMV retinitis may be obtained with a single 20-micrograms cidofovir intravitreal
      injection. In addition, the effect of the drug appears to be maintained after a
      second injection. The effects of cidofovir in causing uveitis and a slight
      lowering of the intraocular pressure require further study.

PMID- 7724171
TI  - Corneal endothelial status 12 to 55 months after excimer laser photorefractive
      keratectomy.
AB  - PURPOSE: To investigate the long-term effect (range, 12-55 months) of
      photorefractive keratectomy (PRK) on the human corneal endothelium. METHODS:
      Specular microscopy of the central corneal endothelium was performed on 106
      patients who underwent PRK to correct myopia. The duration of follow-up varied
      from 12 to 55 months (mean, 33 months; median, 37 months). Patients were divided
      in two groups: group 1 included 32 patients (35 treated eyes) with preoperative
      and postoperative central endothelial images; group 2 included 26 patients from
      group 1 and 74 additional patients with postoperative central endothelial images
      of the treated and untreated fellow eyes. RESULTS: In group 1, preoperative and
      postoperative values were as follows: mean cell density (+/- standard deviation),
      2950 +/- 329 cells/mm2 and 2907 +/- 337 cells/mm2, respectively (P = 0.43);
      polymegathism index, 0.29 +/- 0.06 and 0.28 +/- 0.05, respectively (P = 0.38);
      pleomorphism index, 65.8% +/- 5.6% and 64.2% +/- 5.6%, respectively (P = 0.22);
      figure coefficient index, 0.86 +/- 0.05 and 0.87 +/- 0.02, respectively (P =
      0.20). In group 2, postoperative values of the treated and untreated eyes were as
      follows: mean cell density, 2912 +/- 363 cells/mm2 and 2922 +/- 434 cells/mm2,
      respectively (P = 0.86); polymegathism index, 0.28 +/- 0.05 and 0.30 +/- 0.08,
      respectively (P = 0.04); pleomorphism index, 64.93% +/- 7.49% and 64.07% +/-
      8.31%, respectively (P = 0.45); figure coefficient index, 0.88 +/- 0.03 and 0.88
      +/- 0.03, respectively (P = 0.79). CONCLUSIONS: Photorefractive keratectomy
      caused no damage to the central corneal endothelium. Polymegathism differences in
      treated and untreated eyes could be attributed to modifications in corneal
      metabolism or to a yet unknown mechanism.

PMID- 7724172
TI  - The correlation between incision size and corneal shape changes in sutureless
      cataract surgery.
AB  - PURPOSE: To examine the correlation between incision size and corneal shape
      changes in sutureless surgery using corneal topography. METHODS: Two hundred eyes
      undergoing sutureless cataract surgery were assigned randomly to three groups
      according to the incision size: group A, 3.2-mm incision; group B, 4.0-mm
      incision; and group C, 5.0-mm incision. All eyes were examined by corneal
      topography preoperatively as well as at 1 week and at 1, 3, and 6 months after
      surgery. RESULTS: In the average of difference maps of eyes in the 3.2-mm
      incision group, a wound-related flattening in the peripheral cornea occurred 1
      week after surgery, but decreased rapidly thereafter. Subsequently, no
      significant changes were observed in the cornea after 1 month. In the 4.0-mm
      incision group, with a reduction of the wound-related peripheral flattening, an
      irregular steepening appeared in the lower central cornea 6 months after surgery.
      In the 5.0-mm incision group, a similar steepening in the lower cornea occurred
      just after surgery. This steepening persisted and even extended to the upper
      central cornea in its later postoperative periods. CONCLUSION: The 3.2-mm
      incision hardly produced any irreversible corneal shape changes, whereas both the
      4.0- and 5.0-mm incisions caused a persistent irregular steepening in the central
      cornea.

PMID- 7724173
TI  - Clinical and histopathologic features of corneal dystrophies in Japan.
AB  - PURPOSE: To examine retrospectively the frequency of various corneal dystrophies
      among Japanese patients who underwent keratoplasty or keratectomy at the authors'
      institution over a 34-year period, and to compare the histopathologic features of
      these disorders in the Japanese population with those reported in the Western
      literature. METHODS: Corneal specimens obtained during keratectomy or
      keratoplasty (lamellar and penetrating) performed at the authors' institution
      from 1959 through 1992 were reviewed. Immunohistochemical studies were performed
      using monoclonal antibodies to keratan sulfate and gelsolin, as well as two
      lectins (concanavalin A and wheat germ agglutinin). RESULTS: Of 1259 corneal
      specimens, 159 (12.6%) specimens from a total of 80 patients showed corneal
      dystrophy. Virtually all were non-Fuchs dystrophies; only one case of primary
      Fuchs dystrophy was identified histologically. Granular dystrophy and gelatinous
      drop-like dystrophy were the most common dystrophies identified in the specimens,
      largely because of multiple specimens from individual patients with recurrent
      disease. These two disorders accounted for 86 of the 159 specimens. In terms of
      numbers of patients, lattice dystrophy was the most common (26 patients, 32.5%),
      followed by macular dystrophy (16 patients, 20%), gelatinous drop-like dystrophy
      (15 patients, 18.8%), granular dystrophy (14 patients, 17.5%), and Avellino
      dystrophy (3 patients, 3.75%). Dystrophies represented by only one or two
      patients included congenital hereditary endothelial dystrophy, primary spheroidal
      keratopathy, posterior polymorphous dystrophy, Schnyder crystalline dystrophy,
      and Fuchs dystrophy. CONCLUSIONS: This histopathologic study showed a very low
      incidence of Fuchs dystrophy in the authors' Japanese patient population,
      compared with the incidences seen in studies of populations in Western countries.
      Of the non-Fuchs dystrophies, lattice dystrophy was the most common among the
      patients, although there were large numbers of specimens with granular dystrophy
      and gelatinous drop-like dystrophy due to their recurrent character. The causes
      of clinical and histopathologic differences and similarities among the Japanese
      patients and the patients described in the Western literature are likely related
      to genetic factors, but a complete understanding of their specific mechanisms
      awaits future molecular biologic and genetic elucidation.

PMID- 7724174
TI  - Optical sectioning of the cornea with a new confocal in vivo slit-scanning
      videomicroscope.
AB  - PURPOSE: The purpose of this article is to introduce a newly developed confocal
      in vivo slit-scanning microscope for continuous recording and real-time imaging
      of the various corneal subsegments of the patient's eye with high microscopical
      resolution and adequate contrast. METHODS: One-dimensional confocal slit-scanning
      videomicroscopy of the human cornea was performed with an instrument mainly
      consisting of a scanning module, an image-intensifier video camera, a video
      monitor, and a synchronization unit for matching optical scan and video cycle
      with respect to frequency and phase. Light intensity or fluorescence intensity
      profiles through the cornea could be obtained by microphotometric recording of
      part of the imaging light. An immersion contact technique using an isotonic tear
      replacement liquid with thixotropic properties avoids any mechanical contact
      between the front lens of the microscope objective and the corneal surface.
      RESULTS: In normal human eyes, the corneal micromorphology could be made visible
      with satisfactory lateral and axial resolution and with good contrast. The
      separately focussed sections of the cornea showed the endothelial cells, the
      superficial, intermediary, and basal cells of the epithelium, as well as stromal
      keratocytes and nerves. Even in eyes with significant corneal opacities resulting
      from corneal edema, the endothelial pathology could be imaged with sufficient
      contrast. CONCLUSION: The in vivo slit-scanning videomicroscopy offers real-time
      noninvasive and noncontact serial imaging of corneal subsegments with resolution
      and imaging contrast. Thus, an important step toward using confocal scanning
      microscopy for corneal diagnosis seems to be done.

PMID- 7724175
TI  - Penetrating keratoplasty in cicatrizing conjunctival diseases.
AB  - PURPOSE: The outcome of successful penetrating keratoplasty (PK) typically is
      poor in eyes with end-stage chronic cicatrizing conjunctival diseases such as
      ocular cicatricial pemphigoid (OCP), Stevens-Johnson syndrome, and toxic
      epidermal necrolysis due to immunologically driven conjunctival inflammation
      associated with conjunctival cicatrization and lid abnormalities, severe dry eye,
      and extensive corneal neovascularization. The authors report the results of their
      experience with PK in 13 patients with OCP, Stevens-Johnson syndrome, and toxic
      epidermal necrolysis. METHODS: The authors reviewed the records of patients with
      OCP, Stevens-Johnson syndrome, or toxic epidermal necrolysis seen between 1976
      and 1992. Patients who underwent PK were examined for the purpose of this study.
      Initial and final visual acuity, indications for PK, surgical procedure,
      postoperative therapy, complications, total number of repeat PKs, length of
      follow-up, and the final outcome were recorded. RESULTS: Thirty-two PKs were
      performed in 16 eyes of 13 patients with advanced OCP (6 patients), OCP as a
      sequela of Stevens-Johnson syndrome (2 patients), Stevens-Johnson syndrome (3
      patients), and toxic epidermal necrolysis (2 patients). The indications for the
      first PK were corneal perforation in six eyes (37.5%) and extensive corneal
      scarring in ten eyes (62.5%). Preoperative visual acuity was counting fingers in
      five eyes, hand motions in eight, and light perception in three. Preoperative
      therapy included systemic chemotherapy (8 patients), mucous membrane grafting (9
      eyes), lamellar keratoplasty (2 eyes), superficial keratectomy (1 eye), and
      corneal dye laser photocoagulation (6 eyes). The mean follow-up period was 4.6
      years (3 months-13 years). Eight eyes (50%) had clear grafts, and three eyes
      (18.7%) had 20/200 or better visual acuity at last visit. The major causes of
      graft failure were epithelial defect formation/persistence, stromal ulceration,
      perforation, and graft rejection. CONCLUSIONS: These results indicate that PK may
      be performed for tectonic reasons, but prospects for restoration of sight in
      patients with advanced cicatrizing conjunctival diseases, even after extensive
      preoperative medical and surgical therapy, are limited.

PMID- 7724176
TI  - Orbital infarction syndrome after surgery for intracranial aneurysms.
AB  - BACKGROUND: Global orbital infarction results from ischemia of the intraocular
      and intraorbital structures due to hypoperfusion of the ophthalmic artery and its
      branches. PATIENTS: The authors describe six patients in whom acute proptosis,
      ophthalmoplegia, and blindness developed immediately after surgery for
      intracranial aneurysms. RESULTS: All patients underwent standard frontotemporal
      craniotomies to clip their aneurysms. In all patients, proptosis,
      ophthalmoplegia, and blindness developed in the immediate postoperative period;
      fundus abnormalities included retinal edema, retinal arteriolar narrowing and
      other vascular abnormalities, and pale optic disc swelling. Some patients had
      facial and corneal anesthesia. Ophthalmoplegia and facial anesthesia improved in
      most patients, but none regained any vision in the affected eye. CONCLUSION:
      Orbital infarction syndrome is a rare complication of neurosurgical procedures.
      Increased orbital pressure probably reduced ophthalmic artery and collateral
      arterial perfusion, resulting in ischemia of the intraocular and intraorbital
      structures. There may be multiple factors that compound the risk for orbital
      infarction, and patients with subarachnoid hemorrhage, increased intracranial
      pressure, anomalous arterial or venous circulation, or impaired orbital venous
      outflow seem particularly vulnerable.

PMID- 7724177
TI  - The effect of phenylephrine on Muller muscle. A blepharogram study of eyelid
      motion.
AB  - PURPOSE: The blepharogram technique is used to study the effect of a drug on
      blinking. The authors show that ocular instillation of phenylephrine, a stimulant
      of Muller muscle of the eyelid, accelerates the up phase of the blink. METHODS:
      Motion of a tiny search coil glued to the eyelid moving in a weak magnetic field
      modifies an induced alternating current which is amplified and used to display
      the position of the upper eyelid in degrees on the ordinate of a graph with time
      in milliseconds on the abscissa. The graph is called a blepharogram. Blepharogram
      studies and individual blink analysis show the effect of phenylephrine on eyelid
      motion (blinking). RESULTS: Instillation of phenylephrine accelerated the up
      phase of the blink in all ten experimental subjects. In 65% of subjects,
      phenylephrine also produced or increased newly described N and M blepharogram
      patterns. CONCLUSION: This is the first instrumental detection of the effect of a
      pharmacologic agent on eyelid motion. The blepharogram technique provides insight
      into eyelid physiology and can be used to study any neuromuscular condition that
      affects eyelid motion.

PMID- 7724178
TI  - Congenital fibrosis of the vertically acting extraocular muscles. A new group of
      dominantly inherited ocular fibrosis with radiologic findings.
AB  - BACKGROUND: The authors studied a family with a form of congenital fibrosis of
      the extraocular muscles different from any group previously reported. METHODS: A
      careful examination was done of all affected and all, except one, unaffected
      members of a family of 15 members extending over three generations. The authors
      performed computed tomography on five affected and four unaffected family
      members. RESULTS: All affected family members showed complete loss of vertical
      ocular movement but largely free horizontal movement except for variable
      restriction of adduction in some members. A variable degree of ptosis was
      present, ranging from gross to nil, but with poor levator function and an absent
      Bell phenomenon in all affected members. All affected members showed superficial
      keratopathy, many with corneal scarring. Ocular alignment showed considerable
      variation. Refractive error and amblyopia also were variable. Computed
      tomographic scan indicated reduction in size of the extraocular muscles,
      particularly the superior recti with intracranial ventricular asymmetry in three
      of five patients examined, and abnormality in shape of the eye globes in two
      patients. CONCLUSIONS: The findings indicate a new group best described as
      dominantly inherited congenital fibrosis of the vertical-acting extraocular
      muscles, which is part of the syndrome of congenital ocular fibrosis. Computed
      tomographic scanning suggested that the clinical picture was produced by changes
      present in the orbit, but intracranial ventricular asymmetry also was present in
      some patients and asymmetry of the eye globes in others.

PMID- 7724179
TI  - Sensitivity of laser flare photometry to monitor inflammation in uveitis of the
      posterior segment.
AB  - PURPOSE: Laser flare photometry is a new quantitative method for evaluating
      aqueous flare, making flare the only inflammatory parameter that can be evaluated
      precisely and objectively. The validity of the method already has been
      demonstrated in anterior segment inflammation. The aim of this study is to assess
      the validity and limitations of the method to quantify and monitor inflammation
      in uveitis with predominant involvement of the posterior segment. METHODS: Five
      well-defined conditions with uveitis predominant in the posterior segment were
      analyzed in this study: Behcet uveitis, pars planitis, posterior sarcoidosis,
      posterior pole toxoplasmosis, and birdshot chorioretinopathy. (1) Mean initial
      (pretreatment) flare was determined; (2) in the patients needing systemic steroid
      therapy, introduction of therapy was correlated with evoluting laser flare
      photometry; and (3) in patients with quiescent disease, the predictive value of a
      defined subclinical photometry-detected flare rise for disease recrudescence was
      analyzed. RESULTS: Initial pretreatment flare was 331.8 +/- 47.7 photon counts
      per millisecond (ph/msecond) (mean +/- standard error of the mean) for Behcet
      uveitis, 15.6 +/- 1.3 ph/msecond for pars planitis, 26.9 +/- 4.6 ph/msecond for
      posterior sarcoidosis, 7.5 +/- 1.0 ph/msecond for posterior pole toxoplasmosis,
      5.8 +/- 0.7 ph/msecond for birdshot chorioretinopathy, and 4.7 +/- 0.1 ph/msecond
      for a group of 88 control eyes. A significant flare reduction after start of
      steroid therapy was seen in Behcet uveitis (78% reduction), sarcoidosis (44.8%),
      and pars planitis (51%), but not in toxoplasmosis or in birdshot. A small flare
      rise had a predictive value for disease recrudescence in 27/35 patients
      (predictive value, 0.77; sensitivity rate, 100%). The level of associated blood
      aqueous barrier disruption for reliable follow-up of posterior uveitis was
      empirically determined to be 13 to 15 ph/msecond. CONCLUSION: Laser flare
      photometry was found to be very sensitive to monitor inflammation in uveitis of
      the posterior segment as long as a sufficient level of associated blood-aqueous
      barrier disruption (flare) was present.

PMID- 7724180
TI  - Perfluorocarbon liquid in the management of retinal detachment with proliferative
      vitreoretinopathy.
AB  - PURPOSE: To describe the techniques and results of perfluoro-N-octane used during
      vitrectomy for managing retinal detachment with severe proliferative
      vitreoretinopathy (PVR). METHODS: The authors retrospectively studied 223
      consecutive patients who underwent vitreoretinal surgery for severe PVR (93% D1
      D3). Patients underwent an average of 1.72 prior vitreoretinal surgeries.
      Perfluoro-N-octane was used intraoperatively to flatten the retina, avoiding
      posterior drainage retinotomy, to identify areas of residual retinal traction and
      periretinal membranes, to stabilize the peripheral retina during dissection of
      anterior PVR, and to help determine the extent and location of relaxing
      retinotomies. Extended-term gas tamponade was used in 91% of eyes. All patients
      were followed for a minimum of 6 months. RESULTS: Seventy-eight percent of the
      retinas were reattached posterior to the scleral buckle after a single
      vitreoretinal surgery and 96% were reattached after multiple surgeries. An
      average of 1.24 vitrectomy surgeries were required. The final visual acuity was
      20/400 or better in 74% of eyes and 20/80 or better in 30% (P = 0.004).
      Preoperative hypotony (intraocular pressure < or = 5 mmHg) and multiple prior
      vitreoretinal surgeries were associated with a poor final visual acuity (P = 0.01
      and 0.02, respectively). Preoperative hypotony (intraocular pressure < or = 5
      mmHg) was associated with a greater frequency of relaxing retinotomies (P =
      0.02). Retained perfluoro-N-octane was observed postoperatively in the vitreous
      cavity in 1.3% and subretinal perfluoro-N-octane in 0.9%. CONCLUSION: Experience
      with perfluoro-N-octane has demonstrated its usefulness both diagnostically and
      therapeutically as an intraoperative tool and improved the anatomic and visual
      outcome for retinal detachment complicated by severe PVR.

PMID- 7724181
TI  - Ocular blood flow velocity in age-related macular degeneration.
AB  - BACKGROUND: Changes in the structure of the ocular blood vessels associated with
      age-related macular degeneration (AMD) have been described in some detail, but
      comparatively little is known of the concomitant circulatory changes. The goal of
      this study is to evaluate changes in the ocular circulation that may be
      associated with AMD. METHODS: Ocular blood flow velocities and vessel
      pulsatilities were measured in volunteers with and without AMD using a color
      Doppler imaging unit. Spectral analyses were recorded from the ophthalmic artery,
      central retinal artery and vein, the temporal and nasal short posterior ciliary
      arteries, and the four vortex veins. RESULTS: Adjusting for age, pulsatility
      indices of all arteries were higher in subjects with AMD (central retinal artery
      [P = 0.02]; temporal and nasal short posterior ciliary arteries [P = 0.06 and
      0.002, respectively]; and ophthalmic artery [P = 0.24]). End-diastolic blood flow
      velocity of the short posterior ciliary arteries tended to decrease in the
      presence of AMD. CONCLUSIONS: The combination of increased pulsatility and
      decreased velocity of the short posterior ciliary arteries, observed in the
      presence of AMD, are interpreted as evidence of increased vascular resistance.
      The clinical signs of AMD may be related to degradation of the metabolic
      transport function of the retinal pigment epithelium, resulting from impaired
      choroidal perfusion.

PMID- 7724182
TI  - Progression of retinopathy with intensive versus conventional treatment in the
      Diabetes Control and Complications Trial. Diabetes Control and Complications
      Trial Research Group.
AB  - PURPOSE: To answer the following questions regarding the effect of intensive
      diabetes management on retinopathy in insulin-dependent diabetes mellitus (IDDM):
      (1) Does intensive therapy completely prevent the development of retinopathy? (2)
      Are some states of retinopathy too advanced to benefit from intensive therapy?
      (3) Are the retinopathy endpoints in the Diabetes Control and Complications Trial
      (DCCT) clinically important? and (4) What other factors influence the
      effectiveness of therapy? METHODS: A total of 1441 patients, ranging in age from
      13 and 39 years and with IDDM of 1 to 5 years' duration and no retinopathy at
      baseline (primary prevention cohort) or with 1 to 15 years' duration and minimal
      to moderate nonproliferative retinopathy (secondary intervention cohort), were
      assigned randomly to either intensive or conventional diabetes therapy. Intensive
      therapy, aimed at achieving glycemic levels as close to the normal range as
      possible, included three or more daily insulin injections or a continuous
      subcutaneous insulin infusion, guided by four or more glucose tests daily.
      Conventional therapy included one or two daily injections. Seven-field stereo
      scopic fundus photography was performed every 6 months, for a mean follow-up of
      6.5 years (range, 4-9 years). RESULTS: Intensive therapy reduced the risk of any
      retinopathy (> or = 1 microaneurysm) developing in the primary prevention cohort
      (70% of intensive versus 90% of conventional treatment group; P = 0.002) by 27%.
      It reduced the risk of retinopathy developing or progressing to clinically
      significant degrees by 34% to 76%. Intensive therapy was most effective when
      initiated early in the course of IDDM. It had a substantial beneficial effect
      over the entire spectrum of retinopathy studied in the DCCT and, with rare
      exceptions, in all patient subgroups. CONCLUSION: Although intensive therapy does
      not prevent retinopathy completely, it has a beneficial effect that begins after
      3 years of therapy on all levels of retinopathy studied in the DCCT. The
      reduction in risk observed in the study is translatable directly into reduced
      need for laser treatment and saved sight. Intensive therapy should form the
      backbone of any healthcare strategy aimed at reducing the risk of visual loss
      from diabetic retinopathy.

PMID- 7724183
TI  - Disruption of conserved rhodopsin disulfide bond by Cys187Tyr mutation causes
      early and severe autosomal dominant retinitis pigmentosa.
AB  - PURPOSE: To determine the molecular basis of an early and severe form of
      autosomal dominant retinitis pigmentosa and to characterize the associated
      phenotype. METHODS: Visual function evaluation included electrophysiologic and
      psychophysical testing. Molecular genetic analysis included determining the DNA
      sequence of sections of the rhodopsin gene amplified by polymerase chain reaction
      and screening for changes single-nucleotide by allele-specific oligonucleotide
      hybridization. RESULTS: Affected family members are heterozygous for a unique
      Cys187Tyr rhodopsin mutation which disrupts a highly conserved disulfide bond
      essential to normal rhodopsin function. The retinitis pigmentosa (RP) phenotype
      includes early and severe retinal dysfunction. The full-field electroretinogram
      showed only negligible remaining rod and cone responses by 22 years of age.
      Visual fields were constricted severely by early middle-age years. Macular
      dysfunction caused reduced visual acuity in early adult years, and macular
      atrophy was present in older age. The severity of phenotype generally correlated
      with age, with the exception of an affected 44-year-old patient who had better
      visual acuity, fields, electroretinogram, and dark-adapted thresholds than did
      three younger affected relatives, ranging in age from 22 to 38 years. CONCLUSION:
      An early onset, blinding form of autosomal dominant RP results from a rhodopsin
      Cys187Tyr mutation that eliminates a residue necessary for the formation of a
      highly conserved disulfide bond essential to normal rhodopsin function. The fact
      that one family member is significantly less affected than his younger relatives
      suggests that genetic or environmental factors can modulate the phenotype.

PMID- 7724184
TI  - Histopathologic study of human lacrimal gland. Statistical analysis with special
      reference to aging.
AB  - PURPOSE: Histopathologic changes in human lacrimal gland were investigated, and
      the relation between histopathologic parameters and patient age and sex, as well
      as the histopathologic differences between palpebral and orbital lobes of the
      lacrimal gland were analyzed. METHODS: Samples of the main human lacrimal gland
      that included the palpebral lobes and orbital lobes were taken in 80 autopsies. A
      statistical analysis was made based on light microscope observations with the
      following histopathologic changes as parameters: (1) fibrosis (focal, lobular,
      and diffuse); (2) acinar atrophy (focal, lobular, and diffuse); (3) periductal
      fibrosis; (4) interlobular ductal dilatation; (5) interlobular ductal
      proliferation; (6) lymphocytic foci; (7) periductal lymphocytic infiltration; and
      (8) fatty infiltration. RESULTS: The incidences of these parameters in the
      palpebral and orbital lobes ranged from 3.8% to 35.0%. Lobular fibrosis, lobular
      atrophy, diffuse fibrosis, diffuse atrophy, periductal fibrosis, lymphocytic
      infiltration, and fatty infiltration were more frequent in the orbital lobes with
      statistical significance, whereas interlobular ductal dilatation was more
      frequent in the palpebral lobes. There were statistically significant
      correlations between age and diffuse fibrosis, diffuse atrophy, and periductal
      fibrosis in the orbital lobes of women, and periductal fibrosis in the palpebral
      lobes of men. Diffuse fibrosis and diffuse atrophy in the orbital lobes were
      observed more frequently in elderly women than in elderly men. CONCLUSIONS:
      Various histopathologic changes were observed in the human lacrimal gland.
      Diffuse fibrosis, diffuse atrophy, and periductal fibrosis predominantly found in
      elderly women suggested a relation with keratoconjunctivitis sicca in
      postmenopausal women. The authors speculate the periductal fibrosis is related to
      the decrease in tear fluid outflow with age and that interlobular ductal
      dilatation in the palpebral lobes may be caused by stenosis of the excretory duct
      in the fornix of conjunctiva. Ductal pathologic changes may be important in
      lacrimal gland dysfunction.

PMID- 7724185
TI  - Scleritis associated with systemic vasculitic diseases.
AB  - PURPOSE: Scleritis may occur associated with systemic vasculitic diseases. The
      detection of systemic vasculitic diseases in patients with scleritis is a sign of
      poor general prognosis because it indicates potentially lethal systemic
      complications. This study was undertaken to analyze the ocular prognosis of
      patients with scleritis and the different systemic vasculitic diseases. METHODS:
      Patient characteristics, scleritis type, and ocular complications were evaluated
      in 82 patients with scleritis with systemic vasculitic diseases; comparisons were
      made between patients with scleritis with a specific systemic vasculitic diseases
      and patients with scleritis with the other systemic vasculitic diseases. RESULTS:
      Patients with scleritis with Wegener granulomatosis had more necrotizing
      scleritis (79%, P = 0.0001), decrease in vision (79%, P = 0.014), and peripheral
      ulcerative keratitis (50%, P = 0.0139) than patients with scleritis with the
      other systemic vasculitic diseases. Patients with scleritis with
      spondyloarthropathies had less decrease in vision (8%, P = 0.001) and peripheral
      ulcerative keratitis (0%, P = 0.0256) than patients with scleritis with the other
      systemic vasculitic diseases. Patients with scleritis and systemic lupus
      erythematosus had less necrotizing scleritis (0%, P = 0.0412) than patients with
      scleritis with the other systemic vasculitic diseases. CONCLUSIONS: Ocular
      prognosis of scleritis with systemic vasculitic diseases varies depending on the
      specific systemic vasculitic diseases: scleritis in spondyloarthropathies or in
      systemic lupus erythematosus is usually a benign and self-limiting condition,
      whereas scleritis in Wegener granulomatosis is a severe disease that can lead to
      permanent blindness; scleritis in rheumatoid arthritis or relapsing
      polychondritis is a disease of intermediate severity, which should be monitored
      closely for the development of ocular complications.

PMID- 7724186
TI  - Functional indications for upper and lower eyelid blepharoplasty. American
      Academy of Ophthalmology.
AB  - The purpose of the Committee on Ophthalmic Procedures Assessment is to evaluate
      on a scientific basis new and existing ophthalmic tests, devices, and procedures
      for their safety, efficacy, clinical effectiveness, and appropriate uses.
      Evaluations include examination of available literature, epidemiological analyses
      when appropriate, and compilation of opinions from recognized experts and other
      interested parties. After appropriate review by all contributors, including legal
      counsel, assessments are submitted to the Academy's Board of Trustees for
      consideration as official Academy policy.

PMID- 7724187
TI  - Operative treatment of intra-articular fractures of the calcaneus.
AB  - Displaced intra-articular fractures of the calcaneus remain a diagnostic and
      therapeutic dilemma. The classification of these fractures has been frustrated in
      the past by limitations of radiographic technique. Because of our need to
      consistently analyze our results, a CT scan classification was developed, based
      on the number and location of articular fracture fragments. The authors have
      treated displaced intra-articular calcaneal fractures according to an operative
      protocol using a modified lateral approach, a new plate and lag screws, all
      without the use of bone graft. This article will discuss in depth the treatment
      options available as well as the controversies that surround them.

PMID- 7724188
TI  - Primary subtalar arthrodesis for the treatment of comminuted fractures of the
      calcaneus.
AB  - Comminuted fractures of the calcaneus are extremely difficult to manage, and the
      prognosis after this type of injury is particularly poor. The author has
      approached this problem with precise and anatomic restoration of the height and
      width of the calcaneus with open reduction and internal fixation followed by
      primary subtalar arthrodesis. The surgical technique of primary arthrodesis is
      complex and is described in detail. The rate of arthrodesis and return of
      function is surprisingly good given the magnitude of comminution present and has
      given us renewed hope that these injuries should not be abandoned to later
      salvage attempts at reconstruction.

PMID- 7724189
TI  - Controversies in tarsometatarsal injuries.
AB  - Lisfranc injuries still remain a problematic situation in many clinical cases.
      Although thought to be an uncommon problem, they are actually a common injury.
      This article serves to make the clinician aware of the many recent changes in
      diagnosis and treatment. Emphasis is placed on the precise diagnosis of this
      condition and subsequent follow-up.

PMID- 7724190
TI  - Repair of acute Achilles tendon ruptures.
AB  - Acute Achilles tendon injuries are discussed in terms of various etiologies,
      pathomechanics, and treatment options. Surgical management has evolved to promote
      the athlete's early return to sport utilizing a new suture technique and
      aggressive rehabilitation protocol. The specific training and recovery modalities
      have significantly reduced the morbidity of these injuries by restoring strength,
      range of motion, and preventing disuse atrophy.

PMID- 7724191
TI  - Reconstruction of neglected Achilles tendon injury.
AB  - Chronic Achilles tendon injuries are debilitating injuries that are often
      difficult to treat. A review of previously reported procedures is presented. A
      new technique for repair is presented utilizing a transfer of the flexor hallicus
      longus muscle and tendon to provide a dynamic repair. A review of the clinical
      outcome from this procedure is provided.

PMID- 7724192
TI  - Intramedullary fixation of metatarsal fracture and nonunion. Two methods of
      treatment.
AB  - Fracture of a metatarsal is one of the most common fractures in the foot. The
      location of the fracture depends to some extent on the metatarsal involved, the
      activity, and the foot shape. The goal of treatment is to achieve a successful
      outcome and to avoid prolonged disability. This article covers patient selection,
      surgical technique, and postoperative care.

PMID- 7724193
TI  - Fractures of the tibial plafond. Evolving treatment concepts for the pilon
      fracture.
AB  - Pilon fractures represent a most difficult challenge to the orthopedist.
      Assessment of the degree of energy causing the fracture and careful planning of
      the joint reconstruction will lead to acceptable results in most cases. High
      energy pilon fractures should be treated with great care and respect because the
      risk of complications is high and the likelihood of a good functional ankle is
      less predictable. Detailed and individualized postoperative care coupled with a
      knowledge of salvage procedures, should complications develop, are needed to
      treat the full spectrum of pilon injuries.

PMID- 7724194
TI  - Ring fixators for reconstruction of traumatic disorders of the foot and ankle.
AB  - External fixation methods have an accepted place in orthopedic management of
      problems involving the foot and ankle. Traditionally, reconstruction and
      correction of deformity have been managed with extensive soft-tissue release,
      osteotomies, and arthrodeses. Methods of external fixation have evolved
      dramatically over the past decade with the introduction of the techniques of
      Ilizarov to the Western World. This article covers ankle arthrodesis, burn scar
      contracture, distal tibial deformity, and fractures.

PMID- 7724195
TI  - Soft-tissue coverage for lower-extremity trauma.
AB  - In summary, a rational approach to soft-tissue coverage in the ankle and foot
      should help lower osteomyelitis and bone nonunion rates and yield an excellent
      functional result. In addition to adequate fixation, it is crucial to first
      obtain a clean healthy wound by doing as many debridements as necessary. The goal
      should be to achieve coverage within the first week of injury to avoid the
      sequelae of a later closure; i.e., a potentially much higher infection rate and
      nonunion rate. The reconstructive options range from secondary intention, to
      primary closure, to skin grafts, to local flaps, to microsurgical free flaps. The
      choice should be dictated by the health of the patient, the existing bony and
      neurovascular anatomy, and the desired ultimate objective. Given the currently
      available orthopedic and plastic surgical techniques, it is possible to salvage
      almost any foot or ankle; however, we should not be carried away by our surgical
      armamentorium. If the salvaged extremity will take more than a year to heal, will
      be barely functional, and will be a constant source of pain, then a below-knee
      amputation should strongly be considered. The challenge in the coming decade
      comes both in picking the correct extremity to salvage and in applying the
      techniques described previously to restore it to its preinjury state.

PMID- 7724196
TI  - Controversies in treating talus fractures.
AB  - Controversies of talus fractures are related to the rare incidence of these
      fractures and the even more sparse, clinically based, objective research
      examining treatment outcomes. This article outlines various talus fracture types,
      treatment, and treatment controversies. A discussion section summarizing
      treatment controversies of talar neck fractures, the most common talus fracture,
      is also included.

PMID- 7724197
TI  - Fractures of the proximal fifth metatarsal.
AB  - Most of the controversy regarding fractures of the fifth metatarsal relates to
      injuries sustained in the proximal third of the bone. This article serves as an
      overview of proximal fifth metatarsal fractures, covering the cause, mechanisms
      of injury, and pertinent anatomy of this injury. The author proposes a
      classification scheme for fractures of the fifth metatarsal and gives some
      historical and practical detail with regard to the treatment of each fracture
      type.

PMID- 7724198
TI  - Late reconstruction after failed treatment for ankle fractures.
AB  - The ankle is a very resilient joint, but fractures in this area require accurate
      recognition and aggressive treatment (Fig. 7). Care must be exercised in
      evaluating the radiographics, and further surgical intervention often leads to
      satisfying results. Degenerative changes that may occur years postoperatively can
      turn a "fine" result into an ankle fusion.

PMID- 7724199
TI  - The management of neuroarthropathic fracture-dislocations in the diabetic
      patient.
AB  - Appropriate management for the diabetic patient with a fracture or sprain depends
      on recognition of "at-risk" factors. For patients with stable, minimally
      displaced injuries, conservative modalities (prolonged immobilization and non
      weight-bearing) are sufficient. For patients with unstable or displaced fracture
      dislocations, and whose general condition does not contraindicate surgery, open
      reduction and internal fixation, at times combined with external fixation, is
      recommended. Initial aggressive management can avoid or minimize the disastrous
      sequelae of a destructive neuroarthropathic process and can effect a
      biomechanically sound plantigrade, braceable, and shoeable lower extremity.

PMID- 7724200
TI  - Late reconstruction of the midfoot and tarsometatarsal region after trauma.
AB  - The management of painful arthritis and deformity after trauma to the midfoot
      starts with careful assessment by physical examination and appropriate
      investigation to identify the affected joints. Conservative treatment may be very
      effective and includes the use of NSAIDs, custom insoles with arch support, and a
      rocker-bottom sole with extended steel shank with or without a SACH heel. If this
      treatment fails, usually a year after the injury, then arthrodesis of all the
      symptomatic joints with restoration of the arch and alignment of the weight
      bearing surface is the recommended treatment. The long-term results of these
      fusions may be compromised by the subsequent development of arthritis in adjacent
      joints.

PMID- 7724201
TI  - Nursing practice implications of court decision.

PMID- 7724202
TI  - Staffing documentation = nurse empowerment.

PMID- 7724203
TI  - Inadequate RN staffing issue brought before IOM.

PMID- 7724204
TI  - Assisted suicide creates ethical dilemma for RNs.

PMID- 7724205
TI  - What is the prognosis for national health care reform?

PMID- 7724206
TI  - State health reform: the Oregon Health Plan.

PMID- 7724207
TI  - Defining nurse practitioner scope of practice.

PMID- 7724208
TI  - [Significance of recombinant adenoviruses in experimental gene therapy].
AB  - In the past few years recombinant adenoviruses have emerged as promising
      technology in the gene therapy. They have been used for genetic modification of a
      variety of somatic cells in vitro and in vivo. They offer several advantages over
      other vectors. Replication defective vectors can be produced in very high titers
      (10(11) pfu/ml) thus allowing a substantially greater efficiency of direct gene
      transfer, they have the capacity to infect both replicating and nonreplicating
      cells, and the DNA functions in an extrachromosomal fashion, which eliminates the
      risk of insertional mutagenesis. Several important limitations of adenovirus
      mediated gene transfer are also known, such as the relatively short term
      expression of foreign genes, the dose-related direct toxic effect, and that the
      host immune response to the viral proteins may substantially inhibit the effect
      of repeated infection with recombinant adenoviruses. Recombinant adenoviruses of
      types 2 and 5 are used most frequently as vectors for direct gene transfer. The
      author's experiments with monoclonal antibodies raised against the adenovirus
      hexon proteins revealed the existence of a remarkable homogeneity in the
      antigenic structure among the hexon types of subgenus C (types 1, 2, 5 and 6).
      Besides the genus and type specific epitopes the presence of at least 15
      identical intertype specific epitopes were demonstrated on the surface of the
      hexons. The data suggest that recombinant adenoviruses constructed from the types
      of subgenus C cannot be replaced by each other to avoid the host immune response
      in repeated infections in gene therapy because of their close antigens
      relationships.

PMID- 7724209
TI  - [Correlation between neonatal mortality and hyperinsulinema].
AB  - The authors investigated the correlation among the severity of maternal diabetes,
      the tight control of the maternal blood glucose concentration and the neonatal
      morbidity. Umbilical cord insulin level were measured in 115 newborns, 40 of them
      have diabetic mother. There were significant different in the serum insulin level
      between the low and high morbidity group. The authors suggest the importance of
      the tight blood glucose control during pregnancy, the diagnostic value of
      cardiological ultrasound to decrease the neonatal morbidity.

PMID- 7724210
TI  - [Correlation between ABO and Rh blood groups, serum cholesterol and ischemic
      heart disease in patients undergoing coronarography].
AB  - The associations of the ABO- and Rh-blood groups, the serum cholesterol and the
      extent of the coronary artery disease were examined in 653 patients who underwent
      coronary angiography between 1980 and 1985 in the Hungarian Institute of
      Cardiology. CONCLUSIONS: 1. among the patients with positive coronarography blood
      group A was more frequent and blood group 0 was less frequent than in the
      Hungarian population, 2. in the blood group 0 the left main stenosis, in the
      blood group AB the single-vessel-disease was significantly more frequent, 3. the
      mean serum cholesterol level was almost identical in the ABO-blood groups, but in
      the Rh-negative patients it was significantly higher, showed no difference
      according to age, but closely correlated with the extent of coronary artery
      disease.

PMID- 7724211
TI  - [Multidisciplinary management of breast cancer--(treatment protocol--Albert
      Szentgyorgyi Medical University, Szeged 1994). Organized by the Oncology Team of
      the Albert Szentgyorgyi Medical University].

PMID- 7724212
TI  - [Successfully treated Salmonella enteritidis endocarditis].
AB  - The 60 year old man was admitted because of aphasia and hemiparesis. After
      cranial computed tomography 15 ml parietal hematoma was removed by stereotaxic
      biopsy. The patient had hyperpyrexia, combined mitral vitium and atrial
      fibrillation. There was no symptom of gastroenteritis. Salmonella enteritidis was
      cultured from blood three times. The vegetation was proved by transoesophageal
      echocardiography. Ampicillin + gentamycin, amoxicillin-clavulanate + amikacin
      therapy was ineffective, respectively. During ciprofloxacin therapy of usual dose
      ceased the toxicosis and hyperpyrexia, but remained fever to 38.5 degrees C.
      During 750 mg ciprofloxacin t. i. d. intravenous followed 750 mg t. i. d. per os
      plus 1.5 g cefuroxin t. i. d. intravenous for 46 days became the patient afebrile
      and the vegetation was disappeared. No side effect was observed with
      ciprofloxacin of unusual high daily dose.

PMID- 7724213
TI  - [One-year experience with our antimicrobial protocol].

PMID- 7724214
TI  - Hyperchromatic lenses as potential aids for the presbyope.
AB  - It has been suggested that a 'hyperchromatic' lens which enhanced the
      longitudinal chromatic aberration (LCA) of the eye would increase its depth of
      focus (DOF) and hence might prove a useful aid to presbyopes who have lost their
      natural ability to accommodate for different distances. Experiments are described
      in which high- and low-contrast visual acuity, and contrast sensitivity were
      measured as a function of object vergence using the naked eye and various levels
      of effective lens-eye LCA. It was found that doubling the effective lens-eye LCA
      increased total DOF in the high-contrast acuity task by about 0.5 D, while
      correcting the ocular LCA reduced DOF by about 0.3 D. On the other hand, enhanced
      LCA led to some loss in performance in the low-contrast acuity task and in
      contrast sensitivity.

PMID- 7724215
TI  - Relationship between visual acuity and observation distance.
AB  - The visual acuities of 17 young emmetropes and corrected ametropes were measured
      over the range of 7.5-0.19 m using a Bailey-Lovie chart. Accommodation stimulus
      response measures were also taken over this range using retinoscopy to establish
      whether variations in visual acuity with observation distance could be attributed
      to accommodation behaviour. Tonic accommodation was recorded using the Canon R1
      autorefractor and was compared with visual acuity and stimulus-response results.
      In general, visual acuity was found to be dependent on stimulus distance, being
      significantly reduced for most observers for the closest targets. There were
      three categories of observer performance for visual acuity as a function of
      observation distance; one group showing no change in visual acuity with distance,
      a second showing a flat function for distances 7.55-0.5 m, and then a decrease in
      visual acuity for shorter distances; and a third category that showed a maximum
      visual acuity in the 1.2-1.6 m region. This behaviour was unrelated to individual
      stimulus-response characteristics and there was no significant relationship
      between tonic accommodation and the distance where acuity was best for the third
      category observers.

PMID- 7724216
TI  - Changes in the lower displacement limit for motion with age.
AB  - Previous studies have alleged that the ability to perceive motion remains
      constant with age. We investigated the effect of age on minimum displacement
      thresholds using computer-generated random dot stimuli in 91 healthy, visually
      normal subjects (age range 21-82 years). High and low contrast visual acuity and
      letter contrast sensitivity were also tested. We found that minimum displacement
      thresholds increased significantly at a rate of 0.07 log min arc per decade
      (approximately 17%). The relationship between age and performance was very
      similar for all visual tests.

PMID- 7724217
TI  - Weight of edged lenses in different eyewire shapes and sizes.
AB  - Weights of edged lenses in different eyewire shapes and sizes were studied
      through mathematically generated eyewire shapes. The patterns of weight variation
      are often regular and predictable. The relation of lens weight changes in
      neighbouring sizes of a given eyewire shape and that in different boxed vertical
      lens dimensions of a given general eyewire appearance were established. These
      results were verified with physically edged lenses. Through these relations, it
      will be possible to predict the amount of weight change in a pair of spectacles
      upon changing the frame size and in some cases of eyewire shape modification.

PMID- 7724218
TI  - Two eyes are better than one: binocular enhancement in the contrast domain.
AB  - The purpose of this study was to compare the improvement in visual acuity (VA)
      with the improvement in contrast sensitivity (CS) with two eyes as compared with
      one. Computer generated letter charts were used to measure VA and small letter CS
      (20/25 Snellen equivalent) in 13 emmetropic subjects. Letter size (for VA) and
      contrast (for CS) were varied in equal log steps making the task comparable for
      the two types of measurement. VA improved by an average of 10% (2-3 letters),
      while CS improved by an average of 40% (1 1/2 lines) when tested with two eyes as
      compared with one. Greater sensitivity in the contrast domain prevailed even when
      expressed relative to variability. Using this approach, binocular enhancement was
      identified in 8/13 subjects with CS, but in only 4/13 subjects with VA. Binocular
      enhancement of letter recognition occurs in both size and contrast domains.
      However, the effect is 4x greater when small letters are varied in contrast
      rather than size. Potential applications are considered.

PMID- 7724219
TI  - Optimal temporal frequencies in oscillatory movement hyperacuity measurements of
      visual function in cataract patients.
AB  - Hyperacuity tasks have been suggested for the assessment of potential visual
      function in the presence of cataracts. To test this suggestion, hyperacuity
      thresholds for an oscillating bar were measured in 30 subjects with idiopathic
      cataract and in 24 age-matched normals over a range of oscillation frequencies.
      Each subject's cataract was categorized using the Oxford Clinical Cataract
      Classification and Grading System. Cataract was found to have a significant
      effect on thresholds, although a differential morphological effect on thresholds
      was equivocal. Thresholds at higher temporal frequencies were significantly
      raised when compared to the normal group. The main conclusion to be drawn from
      this study is that motion hyperacuity thresholds appear unaffected by cataract at
      low oscillation frequencies and should be used in preference to higher
      frequencies in the assessment of such patients.

PMID- 7724220
TI  - Effects of exercise on aspects of visual function.
AB  - Strenuous exercise has been reported to affect various aspects of visual and
      ocular function. In the first of two experiments, the effects of cycling, jogging
      and stair running on a range of visual functions were examined. None of these
      forms of exercise was found to have any significant effect on visual acuity,
      refractive error, dark focus, amplitude of accommodation or pupil size. Contrast
      sensitivity (CS), measured by an ascending method of limits (AML), was found to
      improve significantly after cycling and jogging but not after stair running. To
      investigate if the apparent improvement in CS was related to a change in
      'sensitivity' or a change in decision criteria, CS was re-measured before and
      after cycling using both the AML and a 'criterion-free' method of constant
      stimuli (MOCS) procedure. Results obtained using the AML, confirmed the findings
      of the first experiment. However, results obtained using the MOCS procedure
      showed no significant change with exercise. This suggests that the improvement in
      CS found using the AML was due to a shift in subjects' decision criteria rather
      than a physiological change in 'sensitivity'. It is argued that this change in
      decision criteria may be related to the positive mood changes which have been
      found to occur after exercise. This study demonstrates the importance of
      differentiating between changes in 'sensitivity' and changes in decision criteria
      especially where mood or motivation (and hence decision criteria) may be
      confounded with the independent variable. This is particularly important when
      evaluating the effects of exercise on visual function or evaluating the efficacy
      of vision training.

PMID- 7724221
TI  - Fixation disparity and near visual acuity.
AB  - Twenty patients having associated heterophoria values of 2 delta and greater, as
      recorded with a Mallett unit, had their near monocular and binocular visual
      acuities measured. In the latter case, measurements were taken both with the
      associated heterophoria corrected by prisms and without prism correction.
      Bradford Near Vision charts, specially designed to measure visual acuity at near
      in seconds of arc, were used in the acuity measurement. The improvement of
      binocular acuity compared with monocular acuity was less than would occur in
      normal subjects without associated heterophorias. When the associated
      heterophorias were corrected with prisms the improvement in binocular over
      monocular acuity was similar to that found in normal subjects, with zero
      associated heterophoria readings.

PMID- 7724222
TI  - Correcting lens system for perimetry.
AB  - A lens system to correct for both refractive error and perimeter test distance is
      frequently needed for accurate perimetry. Patients often lack appropriate near
      vision corrections and full aperture trial case lenses, when they are available,
      barely cover the central 30 degrees and hence frequently produce lens rim
      artefacts. A special system of correction lenses has been developed for perimetry
      which overcomes these problems. This system is head mounted, being based upon the
      Essilor presbyopia demonstration set, and is suitable for use with most
      perimeters.

PMID- 7724224
TI  - Isogyre formation by isotropic refracting bodies.
AB  - A simple derivation is given of a formula for the intensity pattern produced by a
      diffusely illuminated lens-like body held between a polarizer and an analyser.
      The formula generalizes the results of Charman and of Pierscionek and Chan for a
      dielectric sphere between crossed polaroids. A dark cross is universal for all
      lens-like bodies whose axis of symmetry is normal to the polarizer and analyser.
      Intensity contours are plotted for ellipsoidal lenses.

PMID- 7724223
TI  - Corneal optics from videokeratographs.
AB  - Recent developments in measuring corneal topography make possible an improved
      understanding of corneal optics. It is shown, using a wavefront analysis, that
      optical quantities of interest follow from knowledge of sagittal depths of a
      cornea, and that sagittal depths are provided by or readily found from the output
      of commercially available instruments. The errors for normal corneas are expected
      to be quite small based on measurements on calibration spheres and ellipsoids. As
      an example the optical consequences of a peripheral asymmetry are estimated for a
      particular normal cornea.

PMID- 7724225
TI  - Effect of the constringence of afocal prismatic lenses on monocular acuity and
      contrast sensitivity.

PMID- 7724226
TI  - Reform should include legislative program.

PMID- 7724227
TI  - Opening Dr. Del Grosso's "Black Bag".

PMID- 7724228
TI  - The making of a physician organization.
AB  - In cities and towns across Pennsylvania, many physicians have come to the
      realization that only by working together can they maintain a high level of
      influence over patient care and the business of medical practice. This case
      history focuses on the efforts of one group of physicians that has been helped by
      PennMed Member Services Company (PMSCO). The location and the identity of the
      group have been changed to ensure confidentiality.

PMID- 7724229
TI  - This PUP is not a dog.

PMID- 7724230
TI  - Using my editorial license.

PMID- 7724231
TI  - Networking your way to a new job? Realize its limitations.

PMID- 7724232
TI  - Polymerase chain reaction detection of Trypanosoma cruzi in human blood samples
      as a tool for diagnosis and treatment evaluation.
AB  - Trypanosoma cruzi specific sequences were amplified by the polymerase chain
      reaction from total blood of human chagasic patients and normal individuals. A
      330 bp fragment originating from kinetoplast DNA was specifically detected in
      most chagasic individuals. We tested the sensitivity and specificity of this
      method in normal and affected individuals attending the Evandro Chagas Hospital,
      Rio de Janeiro. The results of these tests were compared with serological
      diagnosis performed using standard techniques, and in some cases with
      xenodiagnosis. We found that none of the serologically negative individuals gave
      any specific amplification product, whereas 55 out of 61 patients previously
      serodiagnosed as chagasic were positive using the PCR method (sensitivity: 90%).
      Xenodiagnosis, which is currently considered to be the most sensitive
      parasitological technique for Chagas' disease diagnosis, detected only 12 out of
      28 serologically positive patients (sensitivity: 43%). The usefulness of the PCR
      method was further investigated with chagasic patients who had received anti
      parasite treatment with benznidazole. It has always been difficult to evaluate
      the incidence of cure in such cases by serology, since a humoral response against
      T. cruzi antigens may remain for years even in the absence of the parasite. We
      observed a positive amplification result in only 9 out of 32 treated patients who
      remained reactive when tested using classical serology. These observations
      suggest that PCR is the most sensitive technique available for direct detection
      of T. cruzi in chagasic patients and that it can be a very useful instrument for
      the follow-up of patients after specific treatment.

PMID- 7724233
TI  - Repetitive proteins from the flagellar cytoskeleton of African trypanosomes are
      diagnostically useful antigens.
AB  - Trypanosome infection of mammalian hosts leads, within days, to a strong early
      response against a small, distinct number of parasite proteins. One of these
      proteins is the variable surface glycoprotein (VSG). Most of the others are
      apparently non-variable, intracellular trypanosome proteins. Two of these
      antigens I2 and I17 are now characterized at the molecular level. Both exhibit a
      highly repetitive amino acid sequence organization, but they show no sequence
      similarity either to each other or to any other proteins known to date.
      Preliminary serological analyses indicate that both allow the early, sensitive
      and specific detection of infections with different species of trypanosomatids,
      making them interesting candidates for the development of diagnostic tools for
      trypanosomiasis detection.

PMID- 7724234
TI  - Detection of parasites of the Leishmania donovani-complex by a polymerase chain
      reaction-solution hybridization enzyme-linked immunoassay (PCR-SHELA).
AB  - A polymerase chain reaction (PCR) based on the detection of the Lmet2 repeat
      sequence specific to members of the Leishmania donovani-complex is described. To
      improve PCR specificity, a post-PCR hybridization step is often performed but
      this usually involves an entirely new procedure with additional manipulations,
      expense and time. We have simplified this post-PCR hybridization by developing a
      strategy which includes the probe in the PCR and enables the hybridization to be
      performed automatically as part of the PCR programme. The hybrids are afterwards
      detected by capture in microtitre wells and colorimetric visualization. This
      method, which we have termed PCR-solution hybridization enzyme-linked immunoassay
      (PCR-SHELA), is rapid, able to detect less than 5 cultured parasites and is
      specific for parasites of the Leishmania donovani-complex. We also describe the
      application of PCR-SHELA to the detection of amastigotes in various tissues of
      infected laboratory animals.

PMID- 7724235
TI  - Genetic and immunological characterization of the microsporidian Septata
      intestinalis Cali, Kotler and Orenstein, 1993: reclassification to
      Encephalitozoon intestinalis.
AB  - The relationships between the Encephalitozoon-like Septata intestinalis and other
      microsporidia that occur in humans; notably Encephalitozoon cuniculi and
      Encephalitozoon hellem, is insufficiently documented using morphological
      descriptions alone. To assess mutual relationships, we have examined other
      phenotypic as well as genetic aspects of S. intestinalis, obtained both from
      tissue culture and clinical specimens, in comparison with a number of other
      microsporidia. Phenotypic characterization was performed by analysis of the
      protein composition and antigenic structure of various microsporidian spores by
      SDS-PAGE and Western blotting. The genetic characterization consisted of the
      determination of the sequence of the S. intestinalis rrs gene encoding the small
      subunit ribosomal RNA (srRNA), restriction fragment length polymorphism (RFLP)
      analysis of amplified rrs genes and establishment of the degree of sequence
      identity between rrs genes of various microsporidian species. The unique sequence
      of rrs of S. intestinalis as well as the distinct RFLP and SDS-PAGE profiles
      indicate that S. intestinalis is clearly different from other human
      microsporidian species. However, its rrs gene shared about 90% sequence identity
      with rrs of both Encephalitozoon spp., E. cuniculi and E. hellem. This is
      remarkably higher than the about 70% identity observed between rrs of
      microsporidian species which belong to different genera and thus suggests that S.
      intestinalis should be regarded as a species of the genus
      Encephalitozoon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724236
TI  - Quantifying parameters in the transmission of Babesia microti by the tick Ixodes
      trianguliceps amongst voles (Clethrionomys glareolus).
AB  - The estimation of two parameters in the transmission of Babesia microti by the
      tick Ixodes trianguliceps amongst small mammals, (1) the duration of infectivity
      in natural hosts and (2) the probability of transmission from an infected to a
      susceptible vole, is described. When B. microti was maintained by direct tick
      transmission, the probability of a complete cycle of transmission via the larval
      nymphal and nymphal-adult transstadial routes was 1.0 and 0.71 respectively, but
      only if the larvae or nymphs had engorged, as distinct from feeding slowly, while
      the source parasitaemia exceeded 2 or 0.2% respectively, but had not yet passed
      the peak level. The duration of this condition for infectivity in voles infected
      by nymphal bites was only 1-4 days, whilst infections delivered by adult ticks
      barely reached the threshold level necessary for successful transmission. When
      syringe passage was introduced into the parasite maintenance schedule (a) the
      probability of transmission declined markedly and (b) the time-course of the
      parasitaemia was altered. If these parameter values are put into a simple model,
      together with field data on tick and host survival rates, it becomes apparent
      that additional factors, such as the highly aggregated distribution of ticks on
      their hosts, must account for the maintenance of B. microti at the levels seen in
      wild small mammal populations.

PMID- 7724237
TI  - Feeding behaviour of tsetse flies (Glossina pallidipes Austen) on Trypanosoma
      infected oxen in Kenya.
AB  - An incomplete ring of electric nets was placed around oxen which were either
      uninfected, infected with Trypanosoma vivax, or infected with T. congolense. The
      numbers of fed and unfed Glossina pallidipes caught on the nets were used to
      estimate the attractiveness of the oxen to tsetse, and the feeding success of the
      tsetse on the oxen. Oxen infected with T. congolense attracted more G. pallidipes
      than the other groups of oxen. Taking into consideration daily variation in the
      abundance or activity of the flies, oxen infected with T. congolense were about
      70% more attractive to G. pallidipes than were uninfected oxen or oxen infected
      with T. vivax. The latter two groups mostly attracted high numbers of G.
      pallidipes on days when the flies were especially abundant or active. The feeding
      success of G. pallidipes declined with increase in the rate at which oxen made
      anti-fly movements. Taking this movement rate into consideration, the feeding
      success of G. pallidipes on oxen infected with T. congolense was approximately
      60% greater than on uninfected oxen or oxen infected with T. vivax. It is
      suggested that vasodilation induced by T. congolense may account for the
      difference in feeding success. The level of parasitaemia of T. congolense or T.
      vivax was not found to affect either the attractiveness of oxen or the feeding
      success on oxen. There was significant daily variation in the mean fat content of
      male G. pallidipes caught around the oxen but not effect of mean daily fat
      content on the proportion of males that fed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724238
TI  - A statistical approach to schistosome population dynamics and estimation of the
      life-span of Schistosoma mansoni in man.
AB  - Dynamic models which predict changes in the intensity of schistosome infection
      with host age are fitted to pre-intervention Schistosoma mansoni data from Kenya.
      Age-specific post-treatment-reinfection data are used to estimate the force of
      infection, thus enabling investigation of the rate of worm death. An empirical
      and statistical approach is taken to the model fitting: where possible,
      distributional properties and function relationships are obtained from the data
      rather than assumed from theory. Attempts are made to remove known sources of
      bias. Maximum likelihood techniques, employed to allow for error in both the pre
      intervention and reinfection data, yield confidence intervals for the worm life
      span (CI95% = 5.7-10.5 years) and demonstrate that the worm death rate is
      unlikely to vary with host age. The possibilities and limitations of fitting
      dynamic models to data are discussed. We conclude that a detailed, quantitative
      approach will be necessary if progress is to be made with the interpretation of
      epidemiological data and the models intended to describe them.

PMID- 7724240
TI  - Chemical guidance of Onchocerca lienalis microfilariae to the thorax of Simulium
      vittatum.
AB  - The behavioural responses of Onchocerca lienalis microfilariae (mf) to tissue
      factors of the surrogate black fly host, Simulium vittatum, were studied using a
      novel in vitro bioassay. Mf accumulated towards thoracic tissues to a density 4
      times higher than towards abdominal tissues, despite the larger surface area and
      volume of abdominal tissues. Mf migrated toward thoracic tissues regardless of
      whether or not contact with thoracic tissues was possible. Therefore, mf directed
      themselves toward the thorax rather than arresting their movement after they make
      contact with thoracic tissues. Chemical cue(s) provided a principal guidance for
      mf to locate thoracic tissues. Mf lost their ability to differentiate thoracic
      and abdominal tissues following addition of thoracic attractant(s) to excised
      abdomens and reversed their differential response when excised thoraces were
      depleted of chemical cue(s). Mf did not respond to salivary gland product, but to
      other thoracic factor(s). Intact thorax that was connected to 1-2 abdominal
      segments attracted considerably less mf than excised thorax. However, intact
      thorax attracted more mf than excised abdomen. Abdominal tissue size did not
      affect thorax attractiveness. Involvement of a large molecular weight protein(s)
      was suggested by the high attractiveness of the 100 kDa Centricon concentrator
      retentate and complete precipitation of attractant(s) by ethanol.

PMID- 7724239
TI  - A molecular phylogeny of the genus Echinococcus.
AB  - Three nucleotide data sets, two mitochondrial (COI and ND1) and one nuclear
      (ribosomal ITS1), have been investigated in order to resolve relationships among
      species and strains of the genus Echinococcus. The data have some unusual
      properties in that mitochondrial heteroplasmy was detected in one strain of E.
      granulosus, and more than one class of ITS1 sequence variant can occur in a
      single isolate. The data failed to support the hypothesis that E. granulosus, as
      it is currently viewed, is a single valid species. Rather, the strains of E.
      granulosus seem to comprise at least three evolutionarily diverse groups, the
      sheep strain group, bovine strain group and horse strain group. Molecular
      distances between them are comparable to, or greater than, molecular evolutionary
      distances observed between recognized species. The affinities of the cervid
      strain of E. granulosus are unclear because of ambiguous data, but this strain
      does not appear to be ancestral to others. E. multilocularis may not be distinct
      from E. granulosus. However, the remaining two species. E. vogeli and E.
      oligarthrus appear distinct and rather distant from the first two. Based on the
      results presented here, taxonomic revision of the genus is clearly warranted.

PMID- 7724241
TI  - GABA in the nervous system of parasitic flatworms.
AB  - In an immunocytochemical study, using an antiserum and a monoclonal antibody
      specific for the amino acid, gamma-aminobutyric acid (GABA), GABA-like
      immunoreactivity (GLIR) has been demonstrated for the first time in parasitic
      flatworms. In Moniezia expansa (Cestoda), GLIR was seen in nerve nets which were
      closely associated with the body wall musculature and in the longitudinal nerve
      cords. In the liver fluke Fasciola hepatica (Trematoda), the GLIR occurred in the
      longitudinal nerve cords and lateral nerves in the posterior half of the worm.
      GLIR was also detected in subtegumental fibres in F. hepatica. The presence of
      GABA was verified, using high-pressure liquid chromatography coupled with
      fluorescence detection. The concentration of GABA (mean +/- S.D.) in M. expansa
      anterior region was 124.8 +/- 15.3 picomole/mg wet weight, while in F. hepatica
      it was 16.8 +/- 4.9 picomole/mg. Since several insecticides and antinematodal
      drugs are thought to interfere with GABA-receptors, the findings indicate that
      GABAergic neurotransmission may be a potential target for chemotherapy in
      flatworms too.

PMID- 7724242
TI  - Iron status of schoolchildren with varying intensities of Trichuris trichiura
      infection.
AB  - The relationship between varying intensities of Trichuris trichiura infection and
      iron status was examined in Jamaican schoolchildren, aged 7 to 11 years. A total
      of 409 children was identified with T. trichiura (epg > 1200). A control group
      comprised 207 uninfected children who were matched by school and class to every
      pair of infected subjects. Blood samples were obtained from 421 children: 264
      infected and 157 controls. Compared to the rest of the children, those with heavy
      infections (epg > 10,000) had significantly lower (P < 0.05) Hb (11.5 +/- 1.3 vs.
      12.1 +/- 1.1 g/dl), MCV (78.6 +/- 6.3 vs. 81.2 +/- 5.5 fl), MCH (26.2 +/- 2.9 vs.
      27.5 +/- 2.5 pg) and MCHC (33.2 +/- 1.5 vs. 33.9 +/- 1.4 g/dl). Similarly, the
      prevalence of anaemia (Hb < 11.0 g/dl) amongst heavily infected children (33%)
      was significantly higher (P < 0.05) than the rest of the sample (11%). These
      differences remained significant after controlling for confounding variables
      including socio-economic status, age, gender, area of residence and the presence
      of Ascaris infections. Differences in red cell count, ferritin, and free
      erythrocyte protoporphyrin were not statistically significant and showed no
      association with the infectious load. These results suggest that in the Jamaican
      children studied, iron deficiency anemia is associated with Trichuris infections
      over 10,000 epg, but not with less intense infections.

PMID- 7724243
TI  - The effects of the nematode peptide, KHEYLRFamide (AF2), on the somatic
      musculature of the parasitic nematode Ascaris suum.
AB  - AF2 is an endogenous RFamide-like peptide from the parasitic nematode Ascaris
      suum. The potent stimulatory effects of this peptide on the somatic musculature
      of Ascaris strongly suggest that it may have an important role in the
      motornervous system. Here we have investigated the possibility that AF2 may
      elicit a stimulatory action on Ascaris muscle by potentiating the actions of the
      excitatory cholinergic motonervous system either pre-synaptically, post
      synaptically or both. In in vitro pharmacological experiments AF2 produced a dose
      dependent increase in the frequency and amplitude of spontaneous contractions of
      Ascaris muscle strip which lasted for more than 1 h after a 3 min application of
      AF2 (10 nM-10 microM; N = 7). In addition, AF2 (100 nM) potentiated the
      contraction elicited by ACh by 43 +/- 9% (P < 0.01; N = 8). In
      electrophysiological recordings from muscle cells, AF2 (10-100 nM; N = 10)
      potentiated the amplitude of EJPs (excitatory junction potentials). For 100 nM
      AF2, the potentiation of the EJP was 218 +/- 48% (N = 7; P < 0.01). This effect
      reversed after a wash of 10 min. AF2 did not potentiate the depolarization of the
      muscle cell elicited by bath applied ACh. These latter two observations are
      consistent with a presynpatic action of AF2. AF2 (10-100 nM) generated
      spontaneous muscle cell action potentials in previously quiescent cells. This
      effect took more than 1 h to wash out. These observations are discussed in terms
      of the paralysis of Ascaris that is elicited by AF2.

PMID- 7724245
TI  - [Digital neurobiology: a new approach to study the nervous system].

PMID- 7724244
TI  - [Ras proteins and promoters of retroelements: the dangerous liaisons].

PMID- 7724246
TI  - [Immunoglobulins E and human immunodeficiency virus infection (HIV)].
AB  - Except for Ig E, serum immunoglobulin abnormalities in persons with human
      immunodeficiency virus (HIV) infection have been well described. Serum IgE levels
      have been shown to rise with progressive disease. The authors evaluated IgE in
      148 HIV-seropositive individuals with or without acquired immunodeficiency
      syndrome (AIDS). Mean serum IgE levels were compared between groups based on
      absolute CD4 lymphocyte counts or clinical status (CDC) and with a seronegative
      control group. Higher serum IgE levels were observed in seropositive-patients. A
      rise in IgE serum is common in patients with HIV infection; it could be link with
      an earlier dysregulation in the IgE synthesis. No correlation was found between
      IgE level and CD4 counts.

PMID- 7724247
TI  - [In vitro antibacterial activity of cefpirome: a new cephalosporin; results of a
      multicenter study].
AB  - The in vitro activity of cefpirome, a new injectable cephalosporin was studied
      against 1,082 clinical isolates in a multicentre study. Minimum inhibitory
      concentrations were determined using an agar dilution method. Cefpirome was
      active against Enterobacteriaceae. On naturally non-producing beta-lactamase
      species, cefpirome was active on most of the strains with MICs < or = 0.5 mg/l,
      including strains producing an acquired penicillinase: E. coli 0.03-0.06, P.
      mirabilis 0.06-0.12, Salmonella spp. 0.06-0.06, Shigella spp. 0.016-0.03. MICs of
      K. pneumoniae (0.06-4) ranged from 0.016 to 32:MICs were high against expanded
      spectrum betalactamase producers strains. Against species producing
      cephalosporinase, cefpirome was also active on most of the strains with MICs < or
      = 0.5: E. cloacae 0.06-2, Citrobacter spp. 0.03-1, S. marcescens 0.06-0.5, P.
      indol + 0.06-0.25, P. stuartii 0.12-0.5. Cefpirome was less active on Pseudomonas
      aeruginosa, (8-32) and on A. baumanii (16-32). MICs of cefpirome were low against
      Haemophilus spp. betalactamase producing or not (0.01-0.03) and M. catarrhalis
      (0.6-4). Activity of cefpirome on methicillin-sensitive staphylococci, was higher
      than other third generation cephalosporins (0.25-2) comparable to that of
      cephalotin and cefamandol. Methicillin-resistant strains should be considered as
      resistant. Pneumococci (0.01-0.03), except for penicillin-R strains, and
      streptococci A, B, C, G (0.01-0.06) were very susceptible. Enterococci were of
      low sensitivity or resistant. Among anaerobes, C. perfringens appeared often
      susceptible, and Bacteroides spp. resistant.

PMID- 7724248
TI  - [Current data on epidermal Langerhans cells].
AB  - The skin may be considered as well as a target and an initiator of self immune
      reactions. Two to 5% of the epidermal cells are Langerhans cells which are the
      only cells to specifically take, process and present the antigens to lymphocytes
      in order to induce an immune response. Such an ability and the location of the
      Langerhans cells enhance the role that they may play in antigenic stimulations or
      immuno-allergic situations. TNF alpha was shown to potentiate the effect of GM
      CSF for the generation of Langerhans cells from their CD34-positive precursors
      found in the cord blood. Originated from the bone marrow, the Langerhans cells
      colonize skin and mucosa where they act as antigen presenting cells (APC) by
      taking, processing antigens, and migrating to lymph nodes in order to sensitize
      lymphocytes. Such a migration was shown, for the first in humans, in an induced
      irritant contact dermatitis. In vitro incubation of isolated Langerhans cells
      induces morphological, phenotypical and functional modifications which make
      Langerhans cells similar to interdigitating cells. Such an observation suggests
      that in vivo Langerhans cells could undergo a maturation when they migrate to
      lymph nodes. Many points remain to be explored in order to clarify the conditions
      which may stimulate or make langerhans migrate and play their immune function.
      For example, cellular interactions or positive/negative effects due to soluble
      mediators (cytokines, neuropeptides) may modulate their role as antigen
      presenting cells. In vitro model of T-cell sensitization confirmed their in vivo
      role of cutaneous surveillance in the recognition and elimination of exogenous
      antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724249
TI  - Four cases of spuriously low WBC count due to in vitro leukocyte agglutination:
      contribution of the hematology analyzer Coulter STKS in detecting this clinically
      misleading artefact.
AB  - Four spuriously lowered WBC counts due to in vitro leukoagglutination were
      reported from an automated cell counter (Coulter STKS). Leukocyte aggregates (3
      to 50 cells), detected in the peripheral blood smears, included different cell
      types, normal (neutrophils, eosinophils, monocytes, lymphocytes) or abnormal
      (lymphoma cells). The phenomenon was associated with either a spurious
      leukoneutropenia or an underestimation of hyperleucocytosis. Leukoagglutination
      was extensively investigated in 3 cases : as shown in several reports,
      leukoagglutination may occur with various features, especially due to temperature
      and anticoagulant dependence. Our four cases reflected this variability.
      Furthermore, one case was found both temperature-dependent and anticoagulant
      independent, a pattern not yet described in the literature. A common STKS graphic
      pattern was found in our 4 cases, suggesting that hematology analyzers such as
      Coulter STKS may be useful to detect leukoagglutination. In conclusion, each
      leukoneutropenia and/or each suggestive graphic pattern must be controlled by
      means of a blood smear examination in order to rule out the possibility of in
      vitro leukoagglutination.

PMID- 7724250
TI  - Platelets, endothelial cells: from autoimmunity to immunomodulation.

PMID- 7724252
TI  - Is the media friend or foe to our children?

PMID- 7724251
TI  - [Fetal-neonatal thrombocytopenia of immunologic origin: current aspects].
AB  - Fetal/neonatal immune thrombocytopenias result from increased platelet
      destruction by maternal antiplatelet antibodies. There is a risk of intracerebral
      haemorrhage and therefore of neurological impairment or death during the
      thrombocytopenic period, especially if a defective platelet function co-exists.
      As no maternal parameter is predictive of the fetal platelet count, the only
      reliable assessment of the fetal status depends on the fetal blood sampling. Only
      in case of materno-fetal alloimmunisation the therapy initiated to reverse fetal
      thrombocytopenia was shown to be effective, but the optimal mode of antenatal
      treatment is currently under study. As the neonatal therapy and the management of
      subsequent pregnancies are somehow different it is mandatory to make the
      distinction between the auto or allo-origin of the fetal thrombocytopenia. The
      definition of high risk pregnancies will be of help for the development of a
      routine screening program.

PMID- 7724253
TI  - Television advertising for health.

PMID- 7724254
TI  - Addressing television sexuality with adolescents.

PMID- 7724255
TI  - Media violence.

PMID- 7724256
TI  - Video game controversies.

PMID- 7724257
TI  - Rock music and music videos.

PMID- 7724259
TI  - Adolescent substance abuse. Risk factors and protective factors.
AB  - The incidence of substance use and abuse by adolescents is influenced by multiple
      risk and protective factors, including genetic influences, predisposition, family
      and peer influences, individual personality traits, and societal influences. The
      potential opportunities for the pediatrician to alter evolving risk factors and
      to foster protective influences are discussed.

PMID- 7724258
TI  - Adolescent substance use. Epidemiology and implications for public policy.
AB  - This article discusses the epidemiology of adolescent substance use, including
      licit drugs and illicit drugs. The focus is on nationally representative samples
      of eighth-, tenth-, and twelfth-grade students from both public and private
      schools. Prevalence rates and recent trends are discussed for subgroups based on
      gender, geographic region, population density, parental education, and racial or
      ethnic groups. Some implications for public policy are presented.

PMID- 7724260
TI  - Basic assessment and screening for substance abuse in the pediatrician's office.
AB  - In summary, it is apparent that discussions on substance abuse should begin at
      the prenatal visit and extend through adolescence. Educational efforts and
      preventive strategies must be given highest priority. Signs and symptoms may be
      subtle, and pediatricians should have a high index of suspicion, particularly for
      high-risk individuals. Practitioners also must be willing to routinely address
      other important psychosocial-medical issues that are closely correlated with the
      use of drugs and alcohol. Laboratory assessment and formal substance abuse
      screening instruments should be used under selected circumstances. Following
      diagnosis, referral to the appropriate resources and coordination of follow-up
      services are important roles for the primary care clinician.

PMID- 7724261
TI  - Clinical toxicology for the pediatrician.
AB  - The pediatrician has at his or her disposal a highly accurate and reliable system
      of drug testing to provide additional information relevant to substance abuse in
      children and adolescents. As always, the judgments engendered in questions such
      as when it is ethical to order such tests, the confidentiality of the results,
      and how to integrate such findings into the overall management of the patient and
      his or her family are much more important and problematic than the technical
      aspects of testing. In selected clinical situations, however, drug testing can
      provide reliable and useful information and is indicated in the diagnosis and
      management of substance abuse in adolescents.

PMID- 7724262
TI  - Principles of brief intervention for adolescent alcohol, tobacco, and other drug
      use.
AB  - Early intervention within a primary health-care setting for problems with ATOD
      use includes screening, assessment, and referral services, and cognitive and
      behavioral brief interventions. All health-care providers who care for
      adolescents should possess the basic skills to communicate effectively with young
      patients and with parents about their concerns about ATOD use problems, should be
      able to identify appropriate substance-abuse services in their communities, and
      should be able to determine the appropriate referral options for a given
      adolescent patients. Some difficulties will be encountered with the introduction
      of behavioral technologies into medical practice. As such, more research is
      needed to determine the most effective approach to incorporate brief
      interventions into the health-care setting. Health-care providers should
      incorporate the principles of effective patient-provider communication and the
      concepts of behavior-changing strategies into their daily practices.

PMID- 7724263
TI  - The assessment of the identified substance-abusing adolescent.
AB  - When an adolescent has been identified as abusing drugs, alcohol, or both, a
      complete assessment of this young person must be completed by qualified health
      professionals before the level of treatment is chosen. With our present state of
      knowledge of substance-abusing adolescents, this assessment must focus on every
      sphere of the child's life, not just the quantity and frequency of the drug use.
      Most substance-abusing young people have experienced deep psychological trauma
      that must be identified and eventually treated. A family evaluation and
      psychological testing are crucial to the evaluation of these adolescents. When
      choosing a treatment facility for a substance-abusing adolescent, it is best to
      select a treatment program that requires family involvement. An adolescent
      treatment program should include treatment of both the family and the child, and
      it must include the goal of abstinence from mood-altering substances as a major
      component of recovery.

PMID- 7724264
TI  - Alcohol and adolescents.
AB  - Alcohol use has persisted over time as the number one drug problem among youth in
      the United States. Many primary care physicians underestimate the seriousness and
      prevalence of teenage alcohol use. The epidemiology of alcohol use among
      adolescents is discussed, as are its dangers and society's attitude toward
      drinking. The effects of alcohol on adolescents are listed. Several types of
      alcoholism are discussed.

PMID- 7724265
TI  - Tobacco use among adolescents. Strategies for prevention.
AB  - Tobacco use is a major public health problem that has its onset during childhood
      and adolescence. To prevent the onset, physicians can reach children and their
      parents in their offices beginning in the prenatal period and continuing through
      adulthood. For pediatricians and other physicians who care for children, NCI
      recommends five office-based activities that begin with the letter A. The 5 As
      include anticipatory guidance, ask, advise, assist, and arrange follow-up visits.
      Elimination of tobacco use requires a comprehensive strategy that includes health
      professional interventions, policy changes, advertising restrictions,
      comprehensive school-based programs, community activities, and advocacy
      approaches. Physicians and health professionals have major roles to play in each
      of these interventions.

PMID- 7724266
TI  - LSD. Its rise, fall, and renewed popularity among high school students.
AB  - LSD is making a comeback nationwide among Caucasian middle-class high school and
      college students. Compared to the mean values during the years 1985 to 1990, an
      approximately 25% increase occurred in lifetime-, annual-, and monthly-use rates
      of LSD, in 1993, according to the annual NIDA high school senior survey. In 1992,
      an increase in LSD-related arrests occurred, as did seizures of larger quantities
      of consumer-ready LSD. The number of LSD-related emergency room visits by
      adolescents increased, and intermittent LSD-related violent behavior, including
      suicide, homicide, and accidental death, were higher than in the previous 5-year
      period. Fewer high school students attribute great danger in trying LSD once or
      twice. The painfully learned lessons about LSD seem, sadly, destined to be
      relearned by the youth of the 1990s.

PMID- 7724267
TI  - Resilience among youth growing up in substance-abusing families.
AB  - This article presents the Challenge Model, a new clinical paradigm for evaluating
      the children of alcoholics and other substance-abusing parents. Unlike
      traditional risk paradigms, the Challenge Model incorporates both the resilience
      and the vulnerabilities that can result from struggling with hardship early in
      life. A developmental vocabulary of strengths is provided for pediatricians to
      use in research, clinical thinking, and treatment and prevention efforts with
      COAs.

PMID- 7724268
TI  - An introduction to ethnic and cultural diversity.
AB  - Ethnic and cultural diversity are important determinants of alcohol and drug use
      patterns and consequences. Cultural differences constitute proximal determinants
      of alcoholism and imply certain differences in attitudes, values, and perceptual
      constructs as a result of different culturally based experiences. Thus, all
      children and adolescents are not equal clinically; transcultural communication is
      necessary for effective identification, diagnosis, and management of substance
      use disorders. Health status antecedents to, and consequences of, substance use
      disorders in ethnic groups of color are examined. Drinking is explored in
      biological, cultural, and social contexts.

PMID- 7724269
TI  - Adolescent treatment. Implications for assessment, practice guidelines, and
      outcome management.
AB  - Treatment for adolescent substance abuse does work. Not only are there clear
      improvements in substance use frequency and in the number of substances used 1
      year after treatment, but also sharp reductions in school and legal problems are
      observed. Improvements in treatment and the continuum of care can be made
      however. Substance abuse treatment cannot end with the formal treatment episode.
      Continuing attendance at support groups, family support, and proactive re-entry
      plans at school all help to ensure continued recovery after treatment. Many
      adolescents receive a large amount of medical care in the year prior to
      admission; however, very few adolescents or their parents list physicians as
      referral sources at admission. Adolescent substance abuse should be identified by
      physicians and thereby treated sooner. Through the use of a three-item screen,
      physicians can reliably identify high-risk adolescents and confidently refer them
      for a formal chemical dependency evaluation. The use of FIRM has provided a means
      of understanding how the interactions of certain pretreatment characteristics
      best predict treatment outcome. Based on such analyses, patient needs can be
      identified, and practice guidelines can be empirically derived through an
      iterative process of implementation and evaluation. As the variability of
      treatment elements increases, treatment process data will become richer. This
      trend will enable providers to further refine the patient-treatment match by
      determining the amounts of exposure to specific treatment elements that are most
      predictive of a positive outcome for a particular group of patients. Efforts have
      been made to classify chemically dependent patients through the use of factor and
      cluster analytic techniques. By first identifying discrete types of patients and
      then measuring how the many services in the treatment experience interact to
      produce favorable outcomes, optimal treatment guidelines could potentially be
      derived for each patient type. Further research in this area would further
      strengthen the bridge between the domains of clinical assessment, practice
      guidelines, and treatment outcome, setting the stage for even more effective
      patient-treatment matching and improved outcomes.

PMID- 7724270
TI  - Preventing relapse. Guidelines for the pediatrician.
AB  - Preventing relapse into substance use means first helping the teenager to develop
      a state of recovery. This involves completing a First Step of a 12-Step program,
      whereby the teenager accepts that drugs and alcohol have been destructive in his
      or her life and that moderate use is impossible. Thus, abstinence is necessary in
      a productive life. Parental support is also established. The two more common
      causes of relapse are being in the presence of alcohol- and drug-using peers and
      the presence of co-existing psychiatric problems.

PMID- 7724271
TI  - Assessment, diagnosis, and treatment of the dually diagnosed adolescent.
AB  - The awareness of the prevalence and presentation of psychiatric diagnoses is
      essential in the quality treatment of adolescent substance abusers. An ongoing
      relationship with a psychiatrist who can be available for consultation as needed
      is helpful. Careful observation and history-taking and appropriate consultation
      results in better detection and treatment of comorbid disorders and, ultimately,
      in better treatment of the patient.

PMID- 7724272
TI  - Vermian agenesis without posterior fossa cyst.
AB  - We report 11 cases of vermian partial agenesis without posterior fossa cyst or
      hemispheric abnormalities. Characteristic MR signs were: absence of the posterior
      lobe, hypoplasia of the anterior lobe, a narrow sagittal cleft separating the
      hemispheres ("buttocks sign") and fourth ventricle deformity. The main clinical
      signs were complex oculomotor dysfunction and developmental delay. None of the
      patients had respiratory symptoms. Consideration is given to the relationship
      between Joubert syndrome and this entity as well as to embryological data.

PMID- 7724273
TI  - Diagnosis of Cushing's disease in children: a challenge for the radiologist.
AB  - Cushing's disease is the most common cause of Cushing's syndrome in children and
      is almost always related to over secretion of ACTH by the pituitary gland. It is
      important to identify a secreting adenoma prior to surgery. Seven cases studied
      with MRI are reviewed. In five cases the MRI findings suggested adenoma. Three
      secreting adenomas were confirmed at surgery. One case was in fact a cyst of the
      pars intermedia, and nothing could be found in the last case. Two patients
      presented with apparently normal findings on MRI, which was confirmed. There is a
      close correlation between identifying an adenoma and the success of surgery.

PMID- 7724275
TI  - Ultrasonographic evaluation of the tongue and the floor of the mouth: normal and
      pathological findings.
AB  - An ultrasonographic study of the tongue and the floor of the mouth was performed
      in 30 healthy children (aged from 1 day to 15 years) in order to assess the
      normal US anatomy of this region. The scans were performed in sagittal and
      coronal planes with a 7.5-mHz transducer. Moreover, 22 children (aged from 1 day
      to 15 years) presenting with various clinical symptoms underwent US examination.
      This series included infectious and congenital diseases. The US findings were
      correlated with surgery and pathology in 19 cases, with the clinical follow-up in
      2 cases and with the nuclear study in 1 case. In each case, US could anatomically
      locate the lesion with very good accuracy. We conclude that US of the tongue and
      the floor of the mouth in children yields overall very good accuracy in the
      investigation of diseases of this region. In this study, our purpose was (1) to
      evaluate the normal sonographic anatomy of the tongue and the floor of the mouth
      in children and (2) to determine whether it was possible to correctly localize
      various lesions and to evaluate their nature in order to guide the therapeutic
      approach.

PMID- 7724274
TI  - Hyperechoic thickened ependyma: sonographic demonstration and significance in
      neonates.
AB  - In the neonate, hyperechoic thickening of the ependyma is believed to be related
      to ventriculitis. Yet, in our experience, this sign is much more often observed
      in association with subacute intraventricular hemorrhage (IVH), without
      infection. Sixty premature neonates were prospectively studied. The observations
      of transfontanellar sonograms (intracranial hemorrhage, ependymal echogenicity,
      and ventriculomegaly) were correlated with the results of MRI, lumbar punctures
      and clinical work-up. Intracranial hemorrhage was detected in 28 patients, and
      hyperechoic thickening of the ependyma was observed in 21 of them, all of whom
      had IVH. In 9 of these 21 patients IVH was diagnosed retrospectively thanks to
      the visualization of the hyperechoic ependyma. In all but one, this sign
      persisted for at least 2 months after disappearance of other signs of IVH. MRI
      demonstrated the presence of hemosiderin and ferritin in ependymal or
      subependymal location only in patients with hyperechoic ependyma. One of our
      patients had in utero diagnosis of IVH owing to the visualization of the same
      hyperechoic aspect of the ependyma. Nine of the neonates with hyperechoic
      ependyma developed ventriculomegaly, and three underwent surgery. Hyperechoic
      thickening of the ependyma in prematures often results from a subacute IVH. It is
      related to hemoglobin catabolites which can be detected by MRI. It does not
      require immediate potentially harmful diagnostic punctures. The presence of this
      hyperechoic rim allows a retrospective diagnosis of IVH and indicates a clinical
      and sonographic follow-up in newborns at risk for secondary hydrocephalus.

PMID- 7724276
TI  - Juvenile chronic arthritis: imaging of the knees and hips before and after
      intraarticular steroid injection.
AB  - Intraarticular steroid therapy in juvenile chronic arthritis (JCA) is performed
      because of high local efficacy with few side effects. Imaging is used for initial
      evaluation and for monitoring of treatment response. The aim of this study was to
      compare imaging findings in diseased hips and knees before and after therapy. A
      prospective study was performed on 10 patients (15 joints) scheduled for
      intraarticular therapy. Pretherapeutic assessment included clinical work-up,
      radiographs, ultrasound (US), and magnetic resonance imaging (MRI) of affected
      joints. Following therapy, clinical and sonographic examinations were performed
      at 1 week and 1 month. MRI was repeated at 1 month. MRI and US demonstrated
      pannus formation and effusion, but differentiation was less distinct on US.
      Popliteal cysts and lymph nodes were visible in both modalities. MRI additionally
      revealed articular cartilage loss and subchondral cysts, not shown by US.
      Epiphyseal overgrowth and osteopenia were best seen radiographically. At present
      MRI is the best tool to assess the inflammatory changes of the joints in JCA.
      Initial staging of the joints may be done with plain films and MRI. US is useful
      to assess effusion and pannus and may be used to monitor treatment response.

PMID- 7724277
TI  - Diaphragmatic paralysis in children: diagnosis by TM-mode ultrasound.
AB  - Diaphragmatic paralysis, a difficult diagnosis in the pediatric age group, has
      classically been made by fluoroscopy or B-mode ultrasound. We report our
      experience with TM-mode exploration. Twenty-seven patients suspected to have
      diaphragmatic paralysis were examined by means of inspiratory and expiratory
      chest radiography, fluoroscopy and B-mode ultrasound. The diaphragmatic echo was
      recorded on TM-tracing during spontaneous breathing using coronal oblique scans.
      Direction, excursion and the pattern of the transition between inspiration and
      expiration were analysed. In 7 patients examination was normal and TM mode
      demonstrated movement of normal direction and excursion with a sharp aspect of
      the transition zone. Diaphragmatic paralysis was present in 11 patients:
      unilateral in 9 and bilateral in 2 cases. TM mode demonstrated paradoxical
      movement, reduced excursion and a smooth transition zone. In 9 patients with
      diaphragmatic dysfunction TM mode demonstrated movement in the normal direction
      but with reduced excursion and a smooth transition zone. Compared to other
      imaging modalities, TM-mode records diaphragmatic movements more objectively. It
      can identify direction of the movement even if they are fast and of weak
      amplitude and in the case of bilateral paralysis. TM can differentiate paralysis
      from dysfunction. Moreover, this low-cost, non-irradiating made of imaging can be
      performed at the bedside and is available on all basic devices.

PMID- 7724278
TI  - Hepatic cysts and hyperechogenicities: perinatal assessment and unifying theory
      on their origin.
AB  - The authors report their experience with the perinatal diagnosis of six cases of
      hepatic cyst and six of liver hyperchogenicities. The in utero diagnosis of
      hepatic cysts was difficult when the cysts were large or subhepatic. A precise
      diagnosis was sometimes achieved only after surgery. Small intraparenchymal cysts
      tended to regress spontaneously. Liver hyperechogenicities were diffuse or
      localized. They were unrelated to liver infection, tumors, meconium peritonitis
      or biliary tract anomaly. Both entities could be related to vascular disruption
      phenomenon (VDP) in which structural anomalies result from damage to normal
      development of embryonic or fetal vessels with anomalies of perfusion to the
      developing organs. The consequences of VDP to the liver are variable depending on
      the time and duration of the phenomenon. Localized infarct or ischemia can
      fibrose or calcify leading to segmental hyperechogenicities. Necrosis with tissue
      reabsorption can be the origin of some (sub)hepatic cysts. When such anomalies
      are detected there should be a careful study of the placentation, and a search
      for potential associated anomalies should be undertaken.

PMID- 7724279
TI  - Blunt renal trauma in children: healing of renal injuries and recommendations for
      imaging follow-up.
AB  - Initial CT grading of renal injury was correlated with the frequency of
      complications and the time course of healing in 35 children. All renal contusions
      (grade 1, 8) and small parenchymal lacerations (grade 2, 8) healed without
      complications. All lacerations extending to the collecting system (grade 3, 9)
      resulted in mild to severe loss of renal function with progressive healing over 4
      months. One of four segmental infarcts (grade 4A), and five of six vascular
      pedicle injuries (grade 4B) resulted in severe loss of renal function.
      Complications, including urinoma (2), sepsis (1), hydronephrosis (1), and
      persistent hypertension (2), were limited to grade 3 and 4 injuries. Our results
      suggest that mild renal injuries do not require follow-up imaging. Major renal
      lacerations and vascular pedicle injuries, however, often result in loss of renal
      function and should be followed up closely due to the risk of delayed
      complications. Follow-up examinations should continue for 3-4 months until
      healing is documented.

PMID- 7724280
TI  - Sonographic detection of internal jugular vein thrombosis after central venous
      catheterization in the newborn period.
AB  - We sonographically investigated the internal jugular veins of 40 children who had
      undergone catheterization of the vein (group A: silastic catheter, n = 24; group
      B: polyurethane catheter, n = 16) in the neonatal period. The average age at
      catheter implantation was 43 +/- 73 days, the average birthweight 2414 +/- 1145
      g, and the average gestational age 34.8 +/- 5.0 weeks. We performed follow-up
      longitudinal and transverse high resolution sonographic scans including routine
      examination of the contralateral jugular vein at a mean age of 3.7 +/- 1.5 years.
      In group A thrombotic alterations were detected in 8 aut of 24 patients. In three
      of these patients we found mild clinical symptoms. In group B thrombotic
      alterations were detected in 1 aut of 16 patients without clinical symptoms. Mean
      birthweight (1815 versus 3313 g) and mean gestational age (32.3 versus 38 weeks)
      were significantly lower and indwelling time of the catheters (18 versus 11 days)
      was significantly longer in group A. Our results indicate that jugular vein
      thrombosis is a frequent long-term complication in neonates after jugular vein
      catheterization. High resolution ultrasonography is an adequate method for
      detecting jugular vein thrombosis and should therefore routinely be performed for
      long-term follow-up.

PMID- 7724282
TI  - Hemolytic uremic syndrome: MR findings of CNS complications.
AB  - MR findings of a patient with hemolytic uremic syndrome involving the CNS are
      described. Abnormal high signal intensity on T2-weighted images combined with
      swelling in the lentiform nucleus, posterior limb of internal capsule, external
      capsule bilaterally, and left extreme capsule was shown on initial MR; a small
      low signal intensity in the left putamen on T1- and T2-weighted images and
      generalized atrophy in the area of high signal intensity on previous T2-weighted
      images was shown on follow-up MR. These findings indicate infarct with focal
      hemorrhage, which is one of the histopathological features of CNS complication in
      hemolytic uremic syndrome.

PMID- 7724281
TI  - Early MR detection of cortical and subcortical hypoxic-ischemic encephalopathy in
      full-term-infants.
AB  - Four observations illustrate the potential of MR imaging in the early depiction
      of multiple types of neuropathologic lesions which may coexist in the full-term
      newborn, upon severe hypoxic-ischemic encephalopathy (HIE). In particular,
      diffuse, postnatal involvement of cerebral cortex and subcortical white matter
      (WM) is demonstrated. Cortical hyperintensity on both proton-density- and T1
      weighted images is probably related to cellular necrosis which is distributed
      diffusely or parasagittally. Hyperintense, frontal, subcortical WM edging on
      proton-density-weighted images results from the increase of water concentration,
      induced either by infarct or by edema. Diffuse WM areas of low intensity on T1
      weighted images and of high intensity on T2-weighted images are presumably
      related to cytotoxic and/or vasogenic edema, proportional to the underlying
      damaged tissues. On follow-up MR examinations, several months later, the
      importance of cortical atrophy and of the myelination delay appeared related to
      the importance of the lesions detected during the postnatal period.

PMID- 7724283
TI  - The "Freddy frog" lateral view of the chest in children. A preliminary report.
AB  - A special new lateral view of the chest, called the "Freddy Frog" view, was used
      in 50 children between the ages of 5 and 7 years. This resulted in optimal
      demonstration of the superior mediastinal and superior bony structures without
      superficial overlying soft tissues and can replace the separate lateral views of
      the neck and chest in cases of stridor.

PMID- 7724284
TI  - Neonatal atypical peripheral atelectasis.

PMID- 7724285
TI  - Bronchial artery aneurysm in hyperimmunoglobulinemia E syndrome.
AB  - A 2-year-old girl presented with a large right middle lobe cavitating lesion,
      complicated by life-threatening hemoptysis secondary to hyperimmunoglobulinemia E
      (hyper IgE) syndrome (Job's syndrome). This proved to be a bronchial artery
      pseudoaneurysm which was successfully embolized.

PMID- 7724286
TI  - Meningitis and sphenoidal sinusitis associated with free gas in the suprasellar
      cistern.
AB  - A case of pneumococcal meningitis in association with sphenoidal sinusitis is
      described. A focal gas collection was demonstrated adjacent to the posterior
      clinoid process. No discernible breach of the sphenoidal sinus walls could be
      shown.

PMID- 7724287
TI  - Fatal brainstem encephalitis caused by Epstein-Barr virus.
AB  - An 8-month-old male infant, previously well, developed acute changes of
      consciousness associated with high fever, vomiting, and respiratory failure.
      Brain CT showed hypodensity of the brainstem, which had shown hyperechogenicity
      on brain ultrasonography. Brainstem encephalitis caused by Epstein-Barr virus
      (EBV) was diagnosed, based on the clinical presentation, neuroimaging and paired
      serological examinations. The patient expired eventually due to central failure.
      We suggest that EBV infection should be a differential diagnosis in cases of
      brainstem encephalitis.

PMID- 7724288
TI  - A patient with facial abnormality, imperforate anus, tetrapolyhypodactyly and
      meningocele: a variable manifestation of the polyoligodactyly/imperforate
      anus/vertebral anomalies syndrome.
AB  - We present a case of an 80-day-old boy with major anomalies consistent with
      polyoligodactyly/imperforate anus/vertebral anomalies (PIV) syndrome. In
      addition, he had facial abnormality, tetrapolyhypodactyly, and sacral
      meningocele. Polydactyly was of postaxial and central types, and all the distal
      phalanges were absent. The association of such anomalies enabled pinpointing of
      the development of this complex anomaly from the 4th to the 6th weeks of the
      embryonic phase. This condition is extremely rare, and the estimated incidence is
      3 in one billion.

PMID- 7724289
TI  - Gastrointestinal bleeding and paraparesis in blue rubber bleb nevus syndrome.
AB  - Blue rubber bleb nevus syndrome (BRBNS), which consists of cutaneous and visceral
      hemangiomas, is a rare disease. Complications such as gastrointestinal (GI)
      bleeding, anemia and coagulopathy have been documented. We report a patient with
      BRBNS who presented with acute paraparesis in addition to GI bleeding and
      coagulopathy.

PMID- 7724290
TI  - Double fetus in fetu: diagnostic imaging.
AB  - Fetus in fetu is a rare pathological condition, presenting as a congenital tumor.
      It consists of a malformed parasitic twin that is found within the body of its
      sibling. Less than 70 cases have been reported and in most of them a definite
      diagnosis was only made during surgery. We present a case with two fetuses in the
      retroperitoneum and describe the criteria to be kept in mind for a correct
      preoperative diagnosis using the current imaging modalities.

PMID- 7724291
TI  - Ureteral quadruplication: the fourth case report.
AB  - Among development abnormalities of the upper urinary tract, ureteral duplication
      is a very common finding while triplication is quite rare. Ureteral
      quadruplication is exceedingly unusual; to our knowledge only three cases have
      been reported over the past 25 years and all of them concerned adult patients. We
      present a case of unilateral quadruplicated ureters in a 9-month-old infant.
      Review of the literature failed to reveal documentation of such a case.

PMID- 7724292
TI  - Severe cystic pulmonary disease associated with chronic Pneumocystis carinii
      infection in a child with AIDS.
AB  - A 3-year-old HIV-positive boy developed Pneumocystis carinii pneumonia (PCP)
      resulting in chronic interstitial pulmonary disease, which persisted for the
      following 3 years; he was essentially asymptomatic and the lung findings had
      therefore been attributed to lymphocytic interstitial pneumonia (LIP). He
      subsequently developed extensive cystic pulmonary disease, documented by CT,
      leading to recurrent pneumothorax and severe pulmonary insufficiency. Lung biopsy
      revealed chronic PCP infection associated with extensive pulmonary fibrosis and
      calcification. This case suggests that Pneumocystis carinii may cause chronic
      progressive pulmonary fibrosis with cyst formation and respiratory failure.

PMID- 7724293
TI  - Pneumatosis intestinalis in a child with AIDS and pseudomembranous colitis.
AB  - Pneumatosis intestinalis (PI) was first reported in three children and one adult
      with acquired immune deficiency syndrome (AIDS) in 1990. The microorganisms
      cultured from these patients included Cryptosporidium, rotavirus,
      cytomegalovirus, and Pseudomonas. We report the fourth child with AIDS and PI,
      and the first with PI to be associated with Clostridium difficile colitis.

PMID- 7724294
TI  - Cerebral infarction in pediatric acquired immunodeficiency syndrome.
AB  - Cerebral infarction is an uncommon complication of AIDS in pediatric patients. We
      have seen three HIV-infected children who developed acute neurological deficits
      due to stroke. Cerebral infarction must be considered in the work-up of a child
      with AIDS who presents with focal neurological deficit, seizure or mental status
      change. Stroke is a complication of HIV infection that occurs in approximately 1%
      of affected children [1]. At autopsy, evidence of cerebral infarction was
      documented in 10-30% of children with HIV infection [2]. We have seen three
      children with focal infarction who are HIV positive.

PMID- 7724295
TI  - The management of febrile infants by primary-care pediatricians in Utah:
      comparison with published practice guidelines.
AB  - OBJECTIVE: To determine primary-care pediatricians' management of febrile infants
      and compare them with published practice guidelines. DESIGN: Case scenarios were
      sent to 194 primary-care pediatricians in Utah, describing three febrile infants,
      ages 21 days, 60 days, and 20 months, corresponding to the three age groups: 0 to
      28 days; 29 to 90 days, and 91 days to 36 months for which the guidelines suggest
      different strategies. RESULTS: Ninety-four pediatricians responded (response
      rate, 48%). Compliance with the guidelines was 39% for the 21 day old, 9.6% for
      the 60 day old, and 75% for the 20 month old. No respondent followed the
      guidelines for all three infants. Performance of tests to determine if an infant
      was low risk varied from 3%, for a stool white cell examination in a febrile 2
      month old with diarrhea, to 75% for a complete blood count in a 20 month old with
      a temperature of 40 degrees C. Compliance did not differ between private and
      academic practitioners. Those in practice less than 5 years (n = 22) were more
      likely than those with more experience to follow the guidelines for the 21 day
      old but not the other two infants. CONCLUSION: Primary-care pediatricians in Utah
      manage febrile infants with fewer laboratory tests and less hospitalization than
      recent practice guidelines developed by an expert panel of academic specialists
      suggest.

PMID- 7724296
TI  - Unintentional perineal injury in prepubescent girls: a multicenter, prospective
      report of 56 girls.
AB  - OBJECTIVE: To determine the pattern of perineal injuries and frequency of hymenal
      involvement resulting from unintentional trauma in prepubescent girls. DESIGN:
      Prospective, multicenter. Observation by skilled observers. Determination of the
      circumstance and physical pattern of injury, with specific attention to the
      hymen. SETTING: Children's emergency department or acute care clinic. PATIENTS:
      Tanner stage 1 girls presenting with acute perineal injury. Criteria for
      unintentional injury: observation of the event or knowledge of the girl's
      engagement in a risky activity (eg, biking or climbing monkey bars) immediately
      before the injury. RESULTS: Fifty-six girls were evaluated. Age range: 1 to 12
      years (median, 6 years; mean, 6.2 years). Associations: bicycle, 39%; other
      outdoor injuries, 25% (climbing apparatus, straddling an object, and falls);
      indoor injuries, 36% (straddling furniture and falls). Most injuries were minor.
      In each group the labia minora was the most frequent structure involved. The
      majority of injuries were anterior or lateral to the hymen. However, in 34% some
      or all of the injuries were posterior to the hymen. Thigh injuries were observed
      only in older children engaged in bicycle riding or outdoor play. In only one
      patient was the hymen involved. That patient was a 2 year old who fell outdoors,
      at a park, abducting her legs in a splits-type mechanism. She had a pinpoint
      abraded area on the hymenal surface at three o'clock. Otherwise, no unique
      pattern of injury was associated with age or circumstance of injury. CONCLUSIONS:
      Hymenal injuries are rarely the result of unintentional injury. The presence of a
      hymenal injury should suggest sexual abuse. Involvement of other perineal
      structures was commonly associated with unintended injury. Given the limited
      resources for prevention, the relative infrequency of perineal injuries and the
      minor nature of most of these injuries, significant preventive efforts are not
      justified.

PMID- 7724297
TI  - Cost-effectiveness of varicella serotesting versus presumptive vaccination of
      school-age children and adolescents.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of presumptive vaccination versus
      serological testing of school-age children (6 to 12 years) and adolescents (13 to
      17 years) with a negative or uncertain history of varicella. DESIGN: Decision
      analysis model based on published and unpublished probabilities and costs.
      PATIENTS: Hypothetical cohorts of 10,000 school-age children and 10,000
      adolescents. MAIN OUTCOME MEASURES: Number of chicken pox cases prevented and
      cost per chicken pox case prevented. RESULTS: For school-age children,
      presumptively vaccinating would prevent 95% of the predicted chicken pox cases,
      would result in net savings when long-term and work loss costs were included, and
      would have a similar cost per case prevented as routinely testing before
      vaccination. For adolescents, presumptively vaccinating would be the most
      effective policy, and would prevent 99% of the projected chicken pox cases. A
      policy of routinely testing before vaccination would be the least effective
      policy for adolescents, preventing 81% of the predicted cases. However, even when
      long-term and work loss costs were taken into account, presumptively vaccinating
      adolescents had a relatively high cost of $329 per chicken pox case prevented and
      extremely high incremental costs per chicken pox case prevented compared with
      policies that involved serological testing. Results for school-age children were
      sensitive to the probability of previously having had chicken pox given a
      negative or uncertain history, to the rate of adherence to follow-up visits, and
      to vaccine price and test price. Results for adolescents were sensitive only to
      the rate of adherence to the first follow-up visit. CONCLUSIONS: Presumptively
      vaccinating all patients with a negative or uncertain history of varicella is
      projected to be a relatively cost-effective policy for school-age children but
      not for adolescents. However, further empirical studies of the accuracy of a
      negative or uncertain history of chicken pox in these age groups are needed.

PMID- 7724298
TI  - Use of a single solution for oral rehydration and maintenance therapy of infants
      with diarrhea and mild to moderate dehydration.
AB  - OBJECTIVE: To compare the efficacy of two commonly used solutions in the
      rehydration of infants with mild to moderate dehydration caused by acute diarrhea
      in the United States. DESIGN AND SETTING: Double-blind, parallel-group,
      randomized study performed at Children's Hospital Medical Center. PATIENTS: Sixty
      infant boys (< or = 2 years old), with mild (< or = 5%) or moderate (6 to 9%)
      dehydration caused by acute diarrhea of less than 1 week's duration were included
      in the study. INTERVENTIONS: Infants were randomly assigned to receive treatment
      with either a glucose-based oral rehydration solution (ORS) (Pedialyte, Ross
      Laboratories, Columbus, OH) or a rice syrup solids-based ORS (Infalyte, Mead
      Johnson Nutritional Group, Evansville, IN). After rehydration was achieved,
      patients entered a maintenance phase during which, in addition to a maintenance
      ORS, breast milk or a soy-based formula was offered; infants older than 1 year
      were also given a lactose-free diet. OUTCOME MEASURES: Rehydration was judged
      clinically. Infants remained on a metabolic bed during the study in to separate
      and quantitate urine and stool output. Therefore, in addition to clinical
      outcome, we compared intake, output and apparent absorption and retention of
      fluid, sodium, and potassium between groups. RESULTS: All patients were
      successfully rehydrated using an ORS without the use of intravenous fluids. No
      differences were detected between treatment groups in time to rehydration,
      percentage of weight gain after rehydration, consumption of ORS to achieve
      rehydration, or stool output. However, the apparent sodium absorption (net intake
      less fecal output) was greater in the Infalyte group than the Pedialyte group
      during the first 24 hours. CONCLUSION: The two maintenance oral electrolyte
      solutions (Pedialyte and Infalyte) most commonly used in the United States are
      effective as rehydration solutions for infants with mild to moderate dehydration.
      We speculate that a strategy for oral rehydration therapy in the United States,
      based on the use of a single solution during the rehydration and maintenance
      phase, might gain additional acceptance by practicing pediatricians and family
      physicians.

PMID- 7724299
TI  - Older children and adolescents living with perinatally acquired human
      immunodeficiency virus infection.
AB  - OBJECTIVE: To describe the clinical, immunologic, and psychosocial
      characteristics of children living with perinatally-acquired human
      immunodeficiency virus (HIV) infection beyond the age of 9 years. METHODS: This
      is a descriptive cohort study of 42 surviving perinatally infected children older
      than 9 years followed at the Children's Hospital Acquired Immunodeficiency
      Syndrome (AIDS) Program (part of a university-based inner city medical center) as
      of June 1993. The study is based on medical record data of clinical, immunologic,
      and psychosocial parameters. RESULTS: The cohort includes 20 boys and 22 girls
      with a mean age of 136 months. The mean age at diagnosis of HIV infection was 88
      months, and 59.5% were asymptomatic at the time of diagnosis. Currently, after a
      mean follow-up period of 48 months from diagnosis, 23.8% remain asymptomatic,
      19.1% have non-AIDS-defining HIV-related symptoms, and 57.1% have AIDS; 85.7% of
      the cohort did not develop HIV-related symptoms until after 48 months of age
      (late-onset prolonged survivors). There was an average annual decline of 71.4
      CD4+ cells/microL in the cohort from the ages of 7 to 16 years, and 21.4% have a
      current CD4+ lymphocyte count of greater than 500 cells/microL, 28.6% between 200
      and 500 cells/microL, and 50% less than 200 cells/microL; 76% are orphaned as a
      result of maternal death, with the majority of the cohort (60%) cared for by
      extended family members. Disclosure of diagnosis has occurred in 57.1%. The vast
      majority of the cohort (76%) are attending regular school, with the remainder in
      special education. CONCLUSIONS: Although close to one quarter of the children and
      adolescents ages 9 to 16 years living with perinatally acquired HIV infection
      described in this cohort remain asymptomatic and have a relatively intact immune
      system, the remainder are living with significant HIV-related symptoms, many of
      which are chronic in nature and have an impact on daily living. The children in
      this cohort had both significant immunologic deterioration and symptomatic
      disease progression during the mean follow-up period of 48 months from the time
      of diagnosis with HIV infection.

PMID- 7724300
TI  - Use of C-reactive protein in differentiation between acute bacterial and viral
      otitis media.
AB  - OBJECTIVES: The objectives of this investigation were: (1) to determine degree of
      elevation of serum C-reactive protein (CRP) in uncomplicated acute otitis media
      (AOM); (2) to compare serum CRP levels in bacterial and viral otitis media; and
      (3) to determine whether a single serum CRP level, obtained early in the course
      of AOM, could be used to differentiate between viral and bacterial otitis media.
      DESIGN AND METHODS: Sera were obtained from otherwise healthy infants and
      children with AOM who were 3 months to 7 years of age between 1989 and 1991.
      Tympanocentesis, bacterial and viral studies of the middle ear fluids, virologic
      studies of nasal wash specimens, measurements of serum antibody titers to
      respiratory viruses, blood counts, and quantitation of serum CRP concentrations
      were performed. After the initial tympanocentesis, an oral antibiotic was given
      for the next 10 days. The patients were clinically reevaluated over next 4 weeks.
      OUTCOME MEASURES: Serum CRP concentrations were compared among subjects with AOM
      who were divided into four groups based on the results of bacteriologic and
      virologic studies: group I, Bacterial infection (n = 82); group II, bacterial and
      viral infections (n = 69); group III, viral infection (n = 12); and group IV, no
      identifiable pathogen (n = 22). RESULTS: There was no statistical difference in
      serum CRP values among the four groups. The ranges of CRP were less than 0.6 to
      22.8, less than 0.6 to 17.8, less than 0.6 to 2.0, and less than 0.6 to 6.8 mg/dL
      in groups I through IV, respectively. However, when CRP values in bacteria
      positive cases were compared with CRP concentrations in bacteria-negative cases
      (1.58 +/- 3.16 vs 0.64 +/- 1.24 mg/dL), the difference was statistically
      significant. Furthermore, a significantly higher proportion of bacteria-positive
      cases had serum CRP concentrations greater than 2 mg/dL, compared with those in
      bacteria-negative cases. There was no correlation between initial CRP values and
      clinical findings and/or the clearance of bacteria from the middle ear. After 10
      days of antibiotic treatment, CRP values returned to normal (< 0.6 mg/dL) in all
      cases. CONCLUSION: In AOM, the range of serum CRP varied from less than 0.6 to
      22.8 mg/dL. High CRP values (> 2.0 mg/dL) were associated with 22% of cases of
      bacterial AOM but only with 6% of nonbacterial AOM. High levels of serum CRP were
      found to be very specific in detecting bacterial AOM, and no cases of viral AOM
      without a concurrent bacterial infection were found to exhibit high serum levels
      of CRP.

PMID- 7724301
TI  - Passive smoke exposure and otitis media in the first year of life. Group Health
      Medical Associates.
AB  - OBJECTIVE: This study examined, in a health maintenance organization population
      of children, the associations between parents' smoking and otitis media (OM) in
      their children while controlling for other known risk factors. METHODS: Healthy
      newborns (1246) in a large health maintenance organization were enrolled at
      birth, and 1013 (81%) were followed prospectively for the first year of life.
      Their medical records were reviewed for the diagnosis of otitis media.
      Information on risk factors for recurrent OM (ROM) was collected, including a
      number of variables related to parental smoking. RESULTS: After controlling for
      other known risk factors for ROM including gender, day care, other siblings in
      the home, parental history of hay fever, and method of feeding, it was found that
      heavy maternal smoking of 20 or more cigarettes per day was a significant risk
      factor for ROM but not for nonrecurrent otitis. Heavy maternal smoking was
      associated with a threefold risk for ROM if the infant weighed less than the mean
      at birth (3.5 kg) after controlling for other risk factors. No association was
      found with paternal smoking. CONCLUSIONS: Heavy maternal smoking is a significant
      risk factor for ROM in the first year of life. This smoking effect seems to be
      stronger among infants of lower birth weight.

PMID- 7724302
TI  - Contribution of heritable disorders to mortality in the pediatric intensive care
      unit.
AB  - OBJECTIVES: To determine the percentage of patients dying in the pediatric
      intensive care unit (PICU) who have heritable disorders and to compare vital
      statistics classification of underlying cause of death with underlying heritable
      disorder identified from medical record review. DESIGN: Retrospective medical
      record review. SETTING: The PICU of a university-affiliated hospital. METHODS:
      Medical records were reviewed for all deaths occurring in the PICA over a 5-year
      period. Further review, including hospital course, clinical findings, and the
      presence or absence of a genetic evaluation, was accomplished for those patients
      found to have a chromosome abnormality, recognized syndrome, single major
      malformation, or unrecognized syndrome. Underlying cause of death classification
      obtained from the Center for Health Statistics, Arkansas Department of Health was
      reviewed to determine the frequency with which the underlying heritable disorder
      was recorded. RESULTS: Fifty-one of 268 (19%) deaths during the study period were
      in patients with heritable disorders. Of these 51 patients, eight (16%) had
      chromosome abnormalities, 17 (33%) had a recognized syndrome, 15 (29%) had a
      single primary defect in development, and 11 (22%) had an unrecognized syndrome.
      Genetic evaluation was carried out on 45% of patients, with the frequency of
      evaluation differing between categories of patients with heritable conditions.
      When underlying cause of death from vital statistics classification was reviewed,
      21 of 51 (41%) records did not include the underlying heritable disorder.
      CONCLUSIONS: Heritable disorders are a frequent cause of mortality in the PICU.
      Vital statistics classification of underlying cause of death in this population
      often fails to identify heritable disorders, leading to an underascertainment of
      these conditions in mortality statistics. Improved cause of death classification
      procedures will be necessary to target public health interventions to etiology
      specific populations.

PMID- 7724303
TI  - Invasive fungal dermatitis in the < or = 1000-gram neonate.
AB  - OBJECTIVE: In 1991, we noted the emergence amongst our extremely low birth weight
      neonates of a new clinical entity, invasive fungal dermatitis, characterized by
      erosive, crusting lesions and a high rate of subsequent systemic fungal
      infection. We sought to define this condition and examine potential risk factors.
      METHODS: Sixteen neonates with invasive fungal dermatitis were seen during a 2
      year period in three Baylor College of Medicine affiliated intensive care
      nurseries. Seven were confirmed cases, with skin biopsy evidence of invasion
      beyond the stratum corneum. Nine had a consistent clinical course and a positive
      potassium hydroxide examination of skin scrapings or isolation of fungi from skin
      or systemic cultures. Three controls were matched to each case by hospital, date
      of admission, and birth weight. Data was collected by retrospective chart review.
      RESULTS: Invasive fungal dermatitis occurred in 5.9% of at-risk infants. Case
      patients had a mean birth weight of 635 g and developed skin lesions at a mean
      age of 9 days (range, 6 to 14). Candida albicans was the most commonly implicated
      pathogen, but other Candida species, Aspergillus, Trichosporon beigelii, and
      Curvularia were also seen. Disseminated infection occurred in 69%, all due to
      Candida sp. Case patients were significantly more premature than controls (mean
      gestation, 24.4 vs 25.9 weeks) and were more likely to be delivered vaginally
      (81% vs 50%). Postnatal steroids were administered to cases (81%) more often than
      controls (46%). Case patients had more prolonged hyperglycemia (as assessed by
      insulin administration) than controls (mean 4.3 vs 2.0 days). CONCLUSIONS:
      Invasive fungal dermatitis is a disease of the smallest, most immature neonates
      and is associated with vaginal birth, steroid administration, and hyperglycemia.
      We speculate that the skin serves as a portal of entry for colonizing fungal
      species and may thus lead to disseminated infection. Methods to improve skin
      barrier function may be useful in preventing this disorder.

PMID- 7724304
TI  - Neonatal pulmonary mechanics and oxygenation after prophylactic amnioinfusion in
      labor: a randomized clinical trial.
AB  - OBJECTIVE: Amnioinfusion has been reported to improve the perinatal outcome of
      pregnancies complicated by decreased amniotic fluid volume, but detailed
      information on its possible adverse effects on neonatal pulmonary mechanics and
      oxygenation is not available. STUDY DESIGN: We evaluated 42 infants with birth
      weights of 2600 to 4320 g and gestational ages of 36 to 44 weeks, who were born
      to mothers enrolled in a prospective, randomized trial of amnioinfusion for
      oligohydramnios in labor. Maternal entry criteria were gestational age 36 weeks
      or older, estimated fetal weight more than 2500 g, oligohydramnios defined as an
      amniotic fluid index of 5 cm or less, and a normal fetal heart rate pattern.
      Evaluation of pulmonary mechanics and oxygen saturation (SaO2) was done with the
      infants breathing room air between birth and day 3 of life. Transpulmonary
      pressure, flow, and tidal volume were recorded simultaneously, and pulmonary
      resistance and lung compliance were calculated. SaO2 was measured for 30 minutes
      with the Nellcor N-200 oximeter and IBM computer oximetry software. RESULTS:
      Evaluation of the data revealed no significant difference between the two groups
      for tidal volume, lung compliance, pulmonary resistance, or work of breathing.
      There were no differences between the two groups in the number of desaturation
      episodes or in percent of desaturations to less than 90%, 85%, or 80% SaO2.
      CONCLUSION: Prior studies have shown amnioinfusion to improve perinatal outcome.
      Our findings demonstrate that amnioinfusion for oligohydramnios in labor does not
      adversely affect neonatal pulmonary mechanics or oxygenation.

PMID- 7724305
TI  - Latex hypersensitivity in children: clinical presentation and detection of latex
      specific immunoglobulin E.
AB  - OBJECTIVE: To better understand the clinical characteristics, diagnosis, and
      possible prevention of immediate hypersensitivity reactions to latex in a
      hospitalized, pediatric patient population. METHODS: We performed a retrospective
      case analysis of the first 35 patients with latex allergy evaluated by our
      service over a 2-year period at our institution. Characteristics of patients and
      clinical reactions were analyzed and the presence of latex-specific
      immunoglobulin E was assessed using in vitro methods. In a limited group of
      patients, the success of strict environmental control and premedication with
      steroids and antihistamines was evaluated for the prevention of latex allergic
      reactions. RESULTS: The majority of our patients had life-threatening reactions.
      In previous reports, most pediatric patients underwent reactions in the
      perioperative period and belonged to two well-recognized "high-risk" patient
      groups (spina bifida and genitourinary malformations). In our series, 21 patients
      (60%) had reactions outside of the operating room setting, and 14 patients (40%)
      had primary diagnoses outside of the previously recognized "high-risk" groups.
      Many patients had a history of multiple surgical procedures, and a history of a
      surgical procedure in the first year of life was very common. A pre-existing
      clinical history of latex allergy was present in only 18 of the 35 patients, and
      a severe or life-threatening allergic reaction was the presenting feature of
      latex allergy in 11 of the 35 patients. Using in vitro assays, we were able to
      detect latex-specific immunoglobulin E in the sera of all but two of our
      patients. Latex gloves and latex-containing intravenous sets were common triggers
      for reactions. When exposure to latex occurs systemically, as through an
      intravenous line, premedication with steroids and antihistamines may fail to
      protect against anaphylaxis. CONCLUSIONS: Our experience indicates that the
      incidence of latex hypersensitivity in children is increasing, that the
      circumstances (patient profile, hospital location, route of exposure) in which
      life-threatening reactions may occur are more broad than previously reported, and
      that a better understanding of both environmental sources of latex antigens and
      host responses to latex exposure are needed for improved prevention of serious
      reactions.

PMID- 7724306
TI  - Acute isoniazid neurotoxicity in an urban hospital.
AB  - OBJECTIVES: To describe the presentation and treatment of acute isoniazid (INH)
      neurotoxicity appearing at an inner-city municipal hospital. DESIGN: Case series.
      PARTICIPANTS: Seven patients (eight patient visits) with an age range of 5 days
      to 14.9 years. RESULTS: At our institution, no children appeared with acute INH
      neurotoxicity in the period 1985 through 1990, whereas seven patients were
      treated from 1991 through 1993. This paralleled the rise in the number of
      children with tuberculous infection and disease seen at our institution, from an
      average 96 per year to 213 per year during these two time periods. All seven
      patients were receiving INH daily for tuberculosis (TB) prophylaxis. Accidental
      ingestion (five episodes) and suicidal attempts (three episodes) accounted for
      these visits. The total amount ingested range from 14.3 to 99.3 mg/kg (mean, 54
      mg/kg). All but one patient presented with afebrile seizures. One patient
      presented twice with seizures. Acute INH neurotoxicity was not suspected on the
      first admission; however, when readmitted 4 weeks later with another seizure, the
      diagnosis of acute INH neurotoxicity was made. INTERVENTION: Intravenous
      pyridoxine was used in five episodes. Because it was not a stocked item in our
      pediatric emergency cart (as well as at another hospital, necessitating a
      transfer of a patient with refractory seizures to our hospital), the average
      delay was 5.8 hours (range, 1.3 to 13 hours) before it was given. Two patients
      with refractory seizures failed to respond to anticonvulsants, and their seizures
      were controlled only after parenteral pyridoxine. CONCLUSIONS: We have seen an
      increased incidence of acute INH neurotoxicity because of the resurgence of TB in
      New York City. Others as well may see a similar rise based on local trends in TB
      infection and disease. Acute INH toxicity should be suspected in children
      presenting with seizures with or without fever. In patients with a known access
      to INH, seizures should be considered to be caused by INH toxicity unless proved
      otherwise. Parenteral pyridoxine, the specific antidote for INH-induced
      refractory seizures, should be readily available in every emergency department in
      the areas similarly experiencing increasing trends of TB.

PMID- 7724307
TI  - Prospective evaluation of complications of dorsal penile nerve block for neonatal
      circumcision.
AB  - OBJECTIVE: To evaluate the complications of the dorsal penile nerve block (DPNB)
      when used for routine neonatal circumcisions. METHODS: All male newborns born in
      a community hospital between November 1, 1989 and August 31, 1990, and
      circumcised after DPNB were evaluated. Questionnaires were completed at the time
      of hospital discharge and at a health supervision visit 2 weeks later. RESULTS:
      Questionnaires were returned for 491 (85%) eligible patients. The only
      complication of DPNB found was bruising at the site of injection in 54 patients
      (11%). All bruising had resolved by the 2-week visit, and none was thought to
      have any clinical significance. CONCLUSION: DPNB is a safe method of decreasing
      the pain and stress of neonatal circumcision.

PMID- 7724308
TI  - Buffered lidocaine: analgesia for intravenous line placement in children.
AB  - OBJECTIVES: To evaluate the effectiveness of intradermal buffered lidocaine as
      analgesia before intravenous line (i.v.) placement in children. METHODS: This was
      a randomized clinical trial undertaken in the emergency department (ED) of a
      regional children's hospital. Participants were children 8 to 15 years old, seen
      in the ED and in need of i.v. lines. They were enrolled by three ED nurses.
      Participants were randomized to receive either intradermal buffered lidocaine or
      no analgesia. Before placement of the i.v. line, patients recorded the amount of
      pain they were in (baseline pain) on a visual analog pain scale. The primary
      outcome measure was amount of pain caused by the initial i.v. attempt, even if
      that attempt was unsuccessful. This was recorded by the participant on a visual
      analog scale. Demographic characteristics, the number of attempts to successful
      placement, and the time required to place the i.v. line were also recorded.
      Differences in pain of initial i.v. attempt and time to place the i.v. line were
      evaluated with the Mann-Whitney U test. Differences in success of i.v. line
      placement were evaluated with the chi 2 test. RESULTS: Fifty-nine patients
      completed the study. Thirty received buffered lidocaine, and 29 received no
      analgesia before i.v. line placement. There was no significant difference between
      the two groups with regard to baseline pain or demographic characteristics. The
      median level of pain of the initial i.v. attempt as measured by the visual analog
      scale was 2.3 in the buffered-lidocaine group and 4.4 in the no-lidocaine group.
      Thirty-three percent of patients in the lidocaine group and 28% percent in the no
      lidocaine group required more than one i.v. attempt. The median time to i.v. line
      placement was 10 minutes in the lidocaine group and 6 minutes in the no-lidocaine
      group. CONCLUSIONS: Use of intradermal buffered lidocaine is an effective way to
      diminish the pain of i.v. line placement in children 8 to 15 years of age. There
      was no difference in i.v. success rate in this study; however, larger numbers of
      patients would be required to detect statistically significant differences. We
      recommend the routine use of intradermal buffered lidocaine for analgesia before
      i.v. line placement in older children in all but emergent situations.

PMID- 7724309
TI  - Adolescents' misinterpretation of health risk probability expressions.
AB  - OBJECTIVE: To determine if differences exist between adolescents and physicians
      in their numerical translation of 13 commonly used probability expressions (eg,
      possibly, might). DESIGN: Cross-sectional. SETTING: Adolescent medicine and
      pediatric orthopedic outpatient units. PARTICIPANTS: 150 adolescents and 51
      pediatricians, pediatric orthopedic surgeons, and nurses. MEASUREMENT: Numerical
      ratings of the degree of certainty implied by 13 probability expressions (eg,
      possibly, probably). RESULTS: Adolescents were significantly more likely than
      physicians to display comprehension errors, reversing or equating the meaning of
      terms such as probably/possibly and likely/possibly. Numerical expressions of
      uncertainty (eg, 30% chance) elicited less variability in ratings than lexical
      expressions of uncertainty (eg, possibly). CONCLUSION: Physicians should avoid
      using probability expressions such as probably, possibly, and likely when
      communicating health risks to children and adolescents. Numerical expressions of
      uncertainty may be more effective for conveying the likelihood of an illness than
      lexical expressions of uncertainty (eg, probably).

PMID- 7724310
TI  - Unrecognized human immunodeficiency virus type 1 infection in a cohort of
      transfused neonates: a retrospective investigation.
AB  - OBJECTIVE: To retrospectively identify unrecognized human immunodeficiency virus
      type 1 (HIV-1) infection among a cohort of children transfused as neonates before
      donated blood was routinely screened for HIV-1 antibody. METHODS: Records at a
      large, private, metropolitan hospital were reviewed to identify children who were
      transfused as neonates between January 1980 and March 1985 and discharged alive
      from the hospital. Multiple data sources were used to locate these children.
      Parents or guardians were contacted, and their children were offered HIV-1
      antibody testing and physical examination. RESULTS: Of the 775 children
      identified as having received transfusions during the project period, 644 (83%)
      were located, and 443 (69%) were evaluated for HIV-1 infection. Among those
      evaluated, 33 (7%) had antibody to HIV-1, including 14 whose infections had not
      been previously diagnosed. At the time of enrollment, 13 children infected with
      HIV-1 were asymptomatic an average of 63 months after transfusion. CONCLUSION:
      HIV-1 antibody testing should be considered for all children, regardless of
      clinical status, who were transfused before routine blood donor screening was
      implemented in March 1985, particularly in areas with a high incidence of
      acquired immunodeficiency syndrome during those years.

PMID- 7724312
TI  - Children's health: racial and ethnic differences in the use of prescription
      medications.
AB  - OBJECTIVES: Although racial and ethnic differences in the use of hospital and
      physician services have been well established, research has not examined the
      relationship between minority status and the use of prescription medications for
      children with some access to the health care system. This study examines
      differences in probability and number of prescribed medications by race and
      ethnicity, and whether the differences remain if socioeconomic factors,
      indicators of need, and number of physician visits are taken into account.
      METHODS: Using data from the 1987 National Medical Expenditure Survey,
      multivariate regression analysis was used to examine the probability of receiving
      a prescription medication and number of medications for two samples of children,
      ages 1 to 5 (N = 1347) and ages 6 to 17 (N = 2155). RESULTS: Descriptive
      statistics indicate that compared with white children, black and Hispanic
      children are less likely to receive a prescribed medication and have on average,
      fewer medications. The multivariate results of this analysis show that those
      differences persist, depending on age group of the child, after adjusting for
      socioeconomic factors, health conditions, and number of physician visits.
      CONCLUSIONS: The relationship between racial and ethnic status and the use of
      prescription medication mirrors other types of services, such as physician
      visits, and affirms that minorities receive fewer services than whites.

PMID- 7724311
TI  - Cardiopulmonary evaluation of exercise tolerance after chest irradiation and
      anticancer chemotherapy in children and adolescents.
AB  - OBJECTIVE: The aim of the study was to evaluate the cardiopulmonary exercise
      tolerance in children and adolescents after chest irradiation and anticancer
      chemotherapy. METHODS: We studied 30 subjectively asymptomatic patients aged 8 to
      25 years treated for pediatric malignancies with chest irradiation (XRT) +/-
      chemotherapy. The median interval since XRT was 7 (range, 2 to 13) years. The
      median XRT dose for mediastinum and/or lungs was 2550 (range, 1000 to 5100) cGy.
      The median cumulative dose of anthracyclines was 250 (range, 0 to 480) mg/m2.
      Cardiac function and exercise tolerance were evaluated by electrocardiography,
      echocardiography, radionuclide cineangiography, and exercise test with gas
      exchange analysis. RESULTS: The patients differed from normal controls in
      systolic indices of myocardial function. In echocardiography, the left
      ventricular contractility was abnormal in 14/30 patients. In radionuclide
      cineangiography, the left ventricular ejection fraction was subnormal in 6/30
      patients, and in 9/30 patients the rise in ejection fraction during exercise was
      inadequate (< 5%). In exercise testing, the mean (+/- SD) maximum workload
      attained was 2.7 (+/- 0.7) watts/kg, and the mean (+/- SD) maximum oxygen
      consumption was 35.4 (+/- 9.7) mL/min/kg. Both variables were < 80% of predicted
      values in 11 patients. CONCLUSIONS: XRT and anticancer chemotherapy very often
      lead to late cardiopulmonary toxicity and impaired exercise tolerance. Although
      in most cases this toxicity seemed to be mild and subclinical, the long-term
      clinical sequels merit further evaluation.

PMID- 7724313
TI  - Inadequate basic preventive health measures: survey of missionary children in sub
      Saharan Africa.
AB  - OBJECTIVE: To determine the prevalence of basic preventive health measures for
      missionary children of sub-Saharan Africa. DESIGN: A retrospective survey of the
      immunization status, water and vegetable treatment, malaria prophylaxis and
      prevention, fluoride prophylaxis, immune globulin (human) prophylaxis, and
      preventive education was completed on 35 missionary children, aged 8 months to 17
      years (7.3 year average), from several sub-Saharan African countries. RESULTS:
      Immunizations were incomplete in 91% of the children. Preventive measures were
      inappropriate for water treatment in 16%, cleaning of vegetables in 35%, malaria
      prophylaxis and prevention in 81%, fluoride prophylaxis in 84%, and immune
      globulin (human) prophylaxis in 94% of veteran children. Blood type was unknown
      in 86% and glucose-6-phosphate dehydrogenase status was unknown in all children.
      Sixty seven percent of the children recently examined received no preventive
      education. CONCLUSIONS: Missionary children of sub-Saharan Africa are not
      provided necessary preventive health services. Physicians and agencies working
      with these children must provide appropriate preventive health guidance and
      services.

PMID- 7724314
TI  - Prenatal tobacco and marijuana use among adolescents: effects on offspring
      gestational age, growth, and morphology.
AB  - OBJECTIVE: This longitudinal study examined the effects of tobacco and marijuana
      use during pregnancy on the gestational age, growth, and morphology of 310
      offspring of adolescents. Data were collected during 1990 through 1993.
      METHODOLOGY: The adolescents were drawn from a prenatal clinic in Pittsburgh, PA.
      They were interviewed at mid-pregnancy and at delivery to obtain information on
      tobacco, marijuana, and other substance use before and during pregnancy. Infants
      were examined 24 to 36 hours after birth. RESULTS: The average maternal age was
      16.1 (range 12 to 18 years); 70% were African-American. Prenatal tobacco use was
      associated with reduced birth weight, length, head and chest circumferences, and
      ponderal index, but not gestational age or the number of morphological
      abnormalities. Prenatal marijuana exposure was associated with reduced
      gestational age. Among whites, first trimester marijuana exposure was associated
      with an increased rate of minor physical anomalies. Prenatal marijuana exposure
      was not associated with any growth outcomes. CONCLUSIONS: These effects of
      prenatal tobacco and marijuana use were prominent despite lower levels of
      prenatal exposure in the offspring of adolescent mothers as compared with the
      offspring of adult mothers from the same clinic. Young maternal age may increase
      the offspring's risk of negative effects from prenatal tobacco and marijuana
      exposure.

PMID- 7724315
TI  - Specification of the neurobehavioral phenotype in males with fragile X syndrome.
AB  - OBJECTIVE: A controlled clinical study was designed to identify the
      neurobehavioral profile that is specific to males with fragile X syndrome.
      DESIGN: Thirty-one males with fragile X syndrome and 30 age and IQ-matched male
      controls were evaluated with instruments that assess multiple domains of adaptive
      functioning and problem behaviors. The Vineland Adaptive Behavior Scales and the
      Aberrant Behavior Checklist were selected for their dimensional scaling of
      behavioral ratings. RESULTS: Parent and Teacher versions of the Aberrant Behavior
      Checklist demonstrated a profile of behaviors specific to males with fragile X
      syndrome characterized by significantly higher levels of hyperactivity,
      stereotypic movements, and unusual speech. The Vineland Adaptive Behavior Scales
      revealed no fragile X-specific profile of adaptive skills development.
      CONCLUSIONS: The distinct pattern of aberrant behavior observed among males with
      fragile X emphasizes the importance of drawing subtype distinctions within the
      classification of individuals with mental retardation on the basis of underlying
      etiology. For clinical research, specifying the fragile X phenotype is a vital
      part in the effort to elucidate the neurodevelopmental pathways of normal
      behavior and psychopathology. Understanding the fragile X symptom pattern is
      essential for designing symptom-specific treatment interventions, as well as for
      research into the efficacy of interventions strategies.

PMID- 7724316
TI  - Telephone calls to an infectious diseases fellow.
AB  - OBJECTIVE: There is no information on the impact and nature of telephone calls
      directed to subspecialists. The main objective was to document prospectively all
      calls directed to a first-year infectious diseases fellow, to determine their
      content, origin, educational value, and time allocation. RESULTS: Three hundred
      fifty-nine calls were received over a 71-day period from March 24 through May 20,
      1992. The mean number of daily calls was 5.1 +/- 3.3. Mean time per call was 7 +/
      5.4 minutes. Cumulatively, 41.7 hours were spent responding to telephone calls.
      The subgroup with the most calls (44.3%) was from pediatricians in practice.
      Seventy percent of calls were for advice about case management. Forty percent of
      calls were considered educational to the fellow. CONCLUSIONS: This study confirms
      the importance of the infectious disease subspecialist as a resource for primary
      care physicians.

PMID- 7724318
TI  - Preventive pediatrics--new models of providing needed health services.

PMID- 7724317
TI  - Screening for retinopathy of prematurity--a problem solved?

PMID- 7724319
TI  - A neonatologist's viewpoint.

PMID- 7724320
TI  - Universal hepatitis B immunization.
AB  - OBJECTIVE: To determine the practices of US nurseries, neonatal intensive care
      units (NICUs), and pediatricians regarding universal hepatitis B vaccination.
      DESIGN: Descriptive cross-sectional survey. PARTICIPANTS: One hundred forty term
      nurseries, 152 NICUs, and 157 pediatricians. Selection procedure. Nurseries and
      NICUs were systematically sampled from the 1992 American Hospital Association
      Guide to provide equal sampling from each region of the country. Pediatricians
      were systematically sampled from a national list of practicing pediatricians
      supplied by Ross Laboratories to provide equal sampling from each state. RESULTS:
      The response rates were 95% (n = 133) for term nurseries, 95% (n = 144) for
      NICUs, and 83% (n = 131) for pediatricians. Sixty-two nurseries (47%) provide
      routine hepatitis B vaccine (HBV) to their infants. Eighty-five NICUs (59%)
      routinely vaccinate their preterm infants; 62 (73%) initiate the series just
      before discharge; and 11 (13%) do so at birth. Principal reasons for not
      vaccinating include cost and a preference to allow the primary-care physician to
      initiate the series. One hundred ten (85%) pediatricians provide universal
      hepatitis B vaccination. Principal reasons for not vaccinating include cost and
      parents opting against vaccination. CONCLUSIONS: More than half of NICUs provide
      HBV routinely to their preterm infants, predominantly just before hospital
      discharge. A minority of NICUs are initiating vaccination at birth, which may
      provide suboptimal seroconversion. Although less than half of participating term
      nurseries are routinely vaccinating before discharge, 85% of pediatricians do
      initiate HBV by two months of age. The principal reasons for not providing
      vaccine are financial.

PMID- 7724321
TI  - Does hunger cause obesity?

PMID- 7724322
TI  - Fatal intramuscular bleeding misdiagnosed as suspected nonaccidental injury.

PMID- 7724323
TI  - Inhaled nitric oxide treatment for stabilization and emergency medical transport
      of critically ill newborns and infants.

PMID- 7724324
TI  - Fluoride supplementation for children: interim policy recommendations. American
      Academy of Pediatrics Committee on Nutrition.

PMID- 7724326
TI  - The pediatrician's role in family support programs. American Academy of
      Pediatrics Committee on Early Childhood, Adoption and Dependent Care.

PMID- 7724325
TI  - Injuries associated with infant walkers. American Academy of Pediatrics Committee
      on Injury and Poison Prevention.

PMID- 7724328
TI  - Cardiac dysrhythmias and sports. American Academy of Pediatrics Committee on
      Sports Medicine and Fitness.

PMID- 7724327
TI  - The role of schools in combatting substance abuse. American Academy of Pediatrics
      Committee on Substance Abuse.

PMID- 7724329
TI  - Mitral valve prolapse and athletic participation in children and adolescents.
      American Academy of Pediatrics Committee on Sports Medicine and Fitness.

PMID- 7724331
TI  - False allegations of sexual touching.

PMID- 7724330
TI  - Recommendations for the use of live attenuated varicella vaccine. American
      Academy of Pediatrics Committee on Infectious Diseases.

PMID- 7724332
TI  - False allegations of sexual touching.

PMID- 7724333
TI  - Kernicterus in a full-term infant: the need for increased vigilance.

PMID- 7724334
TI  - Ultrasound screening for dysplasia of the hip.

PMID- 7724335
TI  - A note of caution about the continuous use of colorimetric end-tidal CO2
      detectors in children.

PMID- 7724336
TI  - No so sunny.

PMID- 7724337
TI  - Are you interested in telephone triage research?

PMID- 7724338
TI  - The plight of American family caregivers: implications for nursing.
AB  - The author conducted a phenomenological study to learn about the caregiving
      experience. In sharing their stories, the caregivers (N = 10) reported common
      themes. The author discusses how psychiatric mental health nurses might become
      sensitive to the needs of caregivers and their families, how public policy is
      failing the American caregiver, and how nurses can become the caregiver's
      advocate.

PMID- 7724339
TI  - Seasonal affective disorder.
AB  - The authors claim psychiatric mental health nurses, particularly those in private
      practice, must recognize symptom patterns of Seasonal Affective Disorder (SAD) so
      that appropriate treatment, including holistic modalities, can be instigated.
      Using a case study presentation, the authors describe the disorder and atypical
      phototherapy treatment.

PMID- 7724342
TI  - The paradox of containing and controlling.

PMID- 7724340
TI  - Serotonin syndrome: a case of fatal SSRI/MAOI interaction.
AB  - The author discusses a relatively new syndrome in which toxic hyperserotonergic
      states can result from the interaction of different classes of antidepressant
      drugs. He also distinguishes between this "serotonin syndrome" and neuroleptic
      malignant syndrome. Using case examples, he demonstrates the potential lethality
      of SS.

PMID- 7724341
TI  - The new statement and standards of psychiatric-mental health clinical nursing.

PMID- 7724343
TI  - The PPC nurse-therapists directory.

PMID- 7724344
TI  - Managed care: friend or foe?

PMID- 7724345
TI  - The pregnant therapist.
AB  - The therapist's pregnancy and subsequent maternity leave affects treatment by
      stimulating many transference and countertransference reactions. Many clients
      will feel abandoned and rejected, and experience sibling rivalry and oedipal
      strivings. The therapist's pregnancy can be an opportunity for clients to work
      through issues of separation and loss, and to make significant progress in
      treatment. Case examples from the author's experience during her first pregnancy
      are used to illustrate how such reactions can be managed in treatment.

PMID- 7724346
TI  - Treatment and service to amputees and other physically disabled patients.

PMID- 7724347
TI  - Benchmark data for elderly, vascular trans-tibial amputees after rehabilitation.
AB  - Benchmark data for lower limb amputees is often limited to young subjects who
      have had their amputations as the result of trauma. The majority of trans-tibial
      amputees rehabilitated are, however, elderly vascular amputees who may have
      different gait characteristics than their younger counterparts. Without
      biomechanical analyses to provide such benchmark data for this group it is not
      possible to compare the effects of different rehabilitation programmes, gait
      training regimens, or prosthetic devices. Twenty elderly vascular trans-tibial
      amputees rehabilitated at The Queen Elizabeth Centre, Ballarat, Australia and at
      least six months post-amputation were measured in respect of kinetic and
      kinematic parameters, and relationships between gait speed, consistency, and
      function were demonstrated. Further, an unexplained vertical ground reaction
      force pattern was demonstrated in faster, more functional amputees.

PMID- 7724348
TI  - Standing balance in trans-tibial amputees following vascular disease or trauma: a
      comparative study with healthy subjects.
AB  - Standing balance measured as sway and standing time both on one and two legs, was
      studied by use of a stable force platform (Kistler) in 36 patients aged 48-87
      years with trans-tibial amputation and 27 healthy subjects matched for age. The
      aim of the study was to compare postural function in standing in two groups with
      unilateral trans-tibial amputations, separating vascular disease from trauma.
      Results revealed that the vascular group had a significantly increased sway in
      the lateral direction compared with the healthy group, when standing on both feet
      close together for 30 seconds, looking straight ahead or blindfolded (p values
      ranging from 0.003 to 0.02). In the sagittal direction the trauma amputees had a
      significantly decreased sway when looking straight ahead, compared to the
      vascular and healthy groups (p values = 0.03). No significant differences in the
      lateral or sagittal direction were seen among the three groups when comparing
      standing on one leg. There was a significant difference, however, in the standing
      time in the one-leg standing test of the vascular group when compared with the
      trauma and healthy groups (p values ranging from 0.0009 to 0.02). In contrast to
      the vascular group, all subjects in the trauma and healthy groups from 48 to 59
      years could stand on the healthy leg for 30 seconds when looking straight ahead,
      and from 60 to 79 years they could stand for 5 seconds. None in the vascular or
      trauma group older than 80 years could stand on the healthy leg for 5
      seconds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724349
TI  - Four-bar linkage prosthetic knee mechanisms: kinematics, alignment and
      prescription criteria.

PMID- 7724350
TI  - A study of 200 cases of congenital limb deficiencies.
AB  - An analysis of 200 patients with congenital limb deficiency who attended the
      Artificial Limb Centre, Pune from January 1984 to April 1990 is presented. This
      group is representative of the congenital limb deficient population of the
      country. The commonest deficiencies were transverse phalangeal total/partial
      deficiency and transverse forearm partial deficiency (below elbow) in upper
      limbs, whereas transverse metatarsal total/partial deficiency and transverse leg
      partial deficiency (below knee) were commonest in lower limbs. Transverse forearm
      partial deficiency was more common in female, while transverse leg partial
      deficiency was more common in male children, 16 patients did not require any
      treatment, 6 needed only surgical correction. Some 30 patients needed surgery
      before prosthetic fitting, while 148 patients required only prostheses. Some 68%
      of patients achieved satisfactory to excellent results; 18% showed poor
      rehabilitation. No definitive cause for the deformities could be isolated;
      however, many parents believed that possible exposure to the eclipse during
      pregnancy was the cause of the deficiency. The eldest child was most affected.

PMID- 7724351
TI  - A pilot study to test the influence of specific prosthetic features in preventing
      trans-tibial amputees from walking like able-bodied subjects.
AB  - The purpose of this pilot investigation was to develop a method to test the
      influence of specific prosthetic features in preventing trans-tibial amputees
      from walking like able-bodied subjects. An able-bodied subject was fitted with a
      patellar-tendon-bearing orthosis incorporating several features of an amputee's
      prosthesis. Kinetic, kinematic and metabolic data were collected as features were
      systematically removed from the orthosis. While wearing the orthosis the gait of
      the able-bodied subject closely simulated trans-tibial amputee gait
      kinematically, kinetically and metabolically. Although it was obvious that the
      various prosthetic features influenced the kinetics and kinematics of gait, they
      were difficult to quantify with only a single subject. However, the two features
      which appeared to have the largest influence in preventing trans-tibial amputees
      from walking like able-bodied subjects were patellar tendon loading and a solid
      ankle.

PMID- 7724352
TI  - [Acute appendicitis].

PMID- 7724353
TI  - [Appendectomy in Sweden. A survey and proposal for quality indicators].
AB  - Something over 12,000 appendectomies are performed in Sweden annually.
      Preoperative diagnosis and outcome were the subject of a survey carried out in
      1991. Based on analysis of the results and a review of recently published
      reports, the article presents proposals for quality markers in appendectomy: the
      frequency of healthy appendixes operated, of perforated appendixes, and of
      postoperative infection.

PMID- 7724354
TI  - [Bleeding complications in oral anticoagulant treatment].
AB  - Vitamin K-antagonists are recommended for the prevention of stroke in patients
      with chronic atrial fibrillation, recent myocardial infarction or prostatic heart
      valves. Anticoagulant therapy is seldom prescribed, however, presumably for fear
      of haemorrhagic sequelae. The risk of bleeding during anticoagulant therapy has
      been evaluated in 10 recent studies of warfarin treatment for the prevention of
      arterial thromboembolism. The mean annual incidences of fatal and major bleeding
      was 0.5 percent and 1.6 percent, respectively, as compared with the placebo
      figures of 0.1 percent and 0.6 percent, respectively. In 3 studies where the
      effect of aspirin has been evaluated the mean annual incidence of fatal and major
      bleeding was 0.2 percent and 0.8 percent, respectively. The figures for warfarin
      therapy where lower than those reported from older studies. The reasons for the
      reduction in incidence may be less intensive anticoagulant treatment than
      formerly, improved laboratory control by the introduction of the International
      Normalized Ratio, and careful pretreatment evaluation of patients selected for
      clinical trials.

PMID- 7724355
TI  - [[Hypertension treatment of elderly men in Iceland].
AB  - Until recently neither the extent of antihypertensive drug usage in Iceland nor
      its distribution among drug classes was known. Of the 1,145 men aged 70-84 years
      alive in 1991, 834 participated in a study carried out by Hjartnavernd, the Heart
      Association. A history of hypertension or the presence of high blood pressure
      when measured at the Associations institute were found in 429 men, of whom 157
      were on medication for hypertension alone: 95 on single drug treatment, 49 on two
      drugs, and five on three drugs, no information being available for the remaining
      eight. The most widely used drugs were diuretics or beta-blockers, of which
      diuretics apparently yielded better results. Of combined regiments, that of beta
      blockers and diuretics was by far the most common, followed by ACE- (angiotensin
      converting enzyme) inhibitors and diuretics, and beta-blockers and calcium
      channel blockers. Thus, both medical and economic factors suggest that diuretics
      should be used in this age group.

PMID- 7724356
TI  - [Care of patients with dementia--a ticking cost bomb?].
AB  - Owing to the increasing number of elderly people, the prevalence of dementia will
      also increase. In 1990, there were about 101,000 people with moderate to severe
      dementia in Sweden, or 6.4 percent of the population over 65 years of age (65+
      pop.). The figure will increase to about 121,000 by the year 2000 (7.7 percent of
      the 65+ pop.), and to 156,000 by 2025 (7.5 percent of the 65+ pop.). The
      corresponding health care costs, which were SEK 30 billion in 1991, are estimated
      to reach SEK 35 billion by 2000, and SEK 46 billion by 2025. Assuming comparable
      increases in the prevalence of dementia in the other Nordic countries, the
      overall number of dementia patients will increase from 247,000 in 1991 to 371,000
      by 2025, and the respective costs from SEK 74 billion to SEK 110 billion.

PMID- 7724357
TI  - [On-duty medical service regulation in Norway, Sweden, Finland and Denmark].
AB  - Out of hours services are under discussion in the Nordic countries, and their
      organisations in Norway, Sweden, Finland and Denmark are compared in the article.
      Only in Denmark all such services are free of charge. In Denmark and in most
      parts of Norway, the patient must first phone a call-in service manned by a
      physician who acts as receptionist cum dispatcher. House calls are very rarely
      made in Sweden and Finland but account for approximately 20 percent of the out of
      hours workload in Norway and Denmark.

PMID- 7724358
TI  - [Somatostatin receptor scintigraphy in medullary thyroid carcinomas, GEP and
      carcinoid tumors].
AB  - For this study, 24 patients with medullary thyroid cancer (MTC) and 10 with
      carcinoid-/GEP-tumours underwent scintigraphy with 123I-Tyr3-octreotide or 111In
      DTPA-D-Phe1-octreotide (Octreoscan) or 99mTc-V-DMSA. Calcitonin and CEA were
      elevated in MTC patients, the other had tumour lesions on CT. Octreoscan
      scintigraphy was positive in 68% of all suspicious cases. On the other hand, 123I
      Tyr3-octreotide showed only rarely positive results. 99mTc-V-DMSA-scans in MTC
      patients were positive in 23%. Liver metastases could be seen only with
      Octreoscan in the non-MTC-group. These results showed better sensitivity of 111In
      labelled octreotide.

PMID- 7724359
TI  - [Iodine deficiency in Southern Badenia--changes during the last 55 years].
AB  - Despite the voluntary iodine prophylaxis in Germany no significant change in the
      iodine supplementation was observed in the last two decades in Southern Badenia.
      This finding relates to urinary iodine excretion as well as to goiter prevalence
      and thyroid volume. The comparison with studies from the 30es and 50es shows
      significant changes, however. There were relevant regional differences in goiter
      prevalence and iodine supply in Southern Badenia at that time. The supply of more
      iodine-containing food could be improved for all walks of life by raising the
      general standard of life. Actually, there are no longer regional differences in
      iodine supply and goiter volume in Southern Badenia. However, in 95% of patients
      investigated the urinary iodine excretion is still below the minimum of 150
      micrograms iodine/g creatinine recommended by WHO.

PMID- 7724360
TI  - [Radioiodine therapy of autonomously functioning thyroid nodules and Graves'
      disease].
AB  - We studied the effects of radioiodine therapy (RIT) for autonomously functioning
      thyroid nodules (AFTNs) and Graves' disease on thyroid function and size up to
      one year after RIT. In 230 patients with AFTNs, a dose of 300 Gy was effective in
      about 90% of the cases 6 months after RIT. Out of 65 patients suffering from
      Graves' disease, 5 patients (8%) had persisting hyperthyroidism 6 months after
      RIT with a dose of 150 Gy. This group consisted exclusively of patients with
      manifest hyperthyroidism at the time of RIT. As determined by ultrasonography 6
      months after RIT, a reduction of thyroid size by about 40% and 60% was observed
      in patients with AFTNs and Graves' disease, respectively.

PMID- 7724361
TI  - [Studies and recommendations on the design ov ROC analyses in nuclear medicine].
AB  - ROC analysis is the method of choice for an objective assessment of diagnostic
      tests; however, it requires large sample sizes. We investigated the influence of
      study design and data analysis on sampling requirements. A sample size of 123 for
      the patient as well as the control group, is required to prove a difference in
      sensitivity of 75% vs 90% (specificity 90%, statistical power 0.8). Analysis with
      the binormal bivariate ROC model allows > 35% reduction in sample size. If the
      patient group is increased the control group can be smaller, and vice versa; here
      the correlated ROC model also allows substantial decreases in sample size. If
      both diagnostic tests are performed in the same patient and control group and
      evaluated with the correlated ROC model, an objective, statistically sound
      assessment of diagnostic performance is possible with relatively small samples.

PMID- 7724362
TI  - [Biokinetics of tumor-affinity yttrium preparations--Part 1].
AB  - Differences of yttrium biokinetics after application to male tumor-bearing mice
      of 87Y-citrate were studied in comparison to a 87Y-NTA-EDTMP-Ca mixture after
      variation of both the manner of application (intraperitoneal vs. intratumoral)
      and the tumor type (mamma carcinoma vs. melanoma). The application of 87Y as NTA
      EDTMP-Ca preparation led--in comparison to the citrate form applied so far--to a
      similar radionuclide tumor accumulation and distinctly lower extratumoral
      radioactivities in liver, spleen and skeleton with clearly more favorable
      tumor/background ratios. Melanomas showed a significantly higher radioactivity
      accumulation (factor 2-3) after injection of 87Y-NTA-EDTMP-Ca than mamma
      carcinomas. Intratumoral application led to high initial radioactivities in the
      tumors. Radioactivity concentrations which are comparable with those after
      intraperitoneal application were achieved within 4 h after intratumoral
      application. The application of the EDTMP-containing mixture promises in
      comparison to the traditional citrate form higher radiation doses in the tumor
      related to the whole-body radiation exposure. The consequences for a possible
      tumor therapy will be further investigated.

PMID- 7724363
TI  - [Performance of a multispect 2 gamma camera for imaging 511-keV gamma rays].
AB  - The performance of a modified Multispect 2 gamma camera, which was supplied with
      two pairs of collimators constructed for imaging positron emitters was tested.
      The measurements involved the determination of sensitivity and of spatial
      resolution. The septal penetration was calculated approximately using two
      different methods. The spatial resolution determined by FWHM as measured by
      planar imaging in water at 10 cm distance from the collimator was evaluated as
      14.0 mm with collimator 511-A and 12.5 mm with collimator 511-B. Using a Gaussian
      fit of the line-spread function septal penetrations of 12% with collimator 511-A
      and of 36% with collimator 511-B were calculated. The absolute system sensitivity
      measured with 18F was 66 cpm with collimator 511-A and 98.7 cpm/37 kBq with
      collimator 511-B. The high sensitivity with collimator 511-B may be explained, at
      least partially, by the high septal penetration.

PMID- 7724364
TI  - [67Ga scintigraphy in acute sarcoidosis with Heerfordt's syndrome].
AB  - Sarcoidosis is a chronic multisystem disorder of unknown etiology characterized
      by non-caseating epitheloid granulomas. We report a case of a 29-year old female
      with acute sarcoidosis and Heerfordt's syndrome (parotid enlargement, anterior
      uveitis and facial nerve palsy) who had a typical clinical constellation but no
      histologic criteria of a granulomatous inflammatory process in transbronchial
      lung biopsy. 67Ga scintigraphy revealed such a typical pattern of accumulation
      that sarcoidosis could be diagnosed despite negative histological findings.

PMID- 7724365
TI  - [Thallium scintigraphy of the myocardium. Uniform research protocols of the
      Austrian Society for Nuclear Medicine].
AB  - A uniform protocol for thallium scintigraphy of the myocardium has been issued in
      Austria to avoid difficulties in interpreting results and to avoid repeated
      examinations to save expenses and radiation burden. From the beginning of 1995
      this protocol will be used in the Austrian departments of Nuclear Medicine,
      differences from this protocol have to be mentioned separately. In this protocol
      the procedure of examination, bicycle and pharmacological stress testing and
      vasodilatation, acquisition techniques for planar and SPECT imaging, data
      processing and quality control of devices are defined.

PMID- 7724367
TI  - The NT guide to PREP.

PMID- 7724366
TI  - [Tc-99m-labeled anti-CEA antibodies in intraoperative diagnosis of colorectal
      cancer].
AB  - Stage-adjusted treatment of colorectal tumors requires precise knowledge of the
      extent of the underlying disease. Reliable staging is mandatory for
      intraoperative treatment planning. In this prospective trial monoclonal
      antibodies to CEA were labeled with 99mTc as tracer. Twenty patients were studied
      intraoperatively with a hand-held gamma detector. The results were compared to
      those obtained by all other diagnostic modalities and they were then confirmed by
      histopathology. Intraoperative scanning can reliably identify all tumor deposits
      and can confirm the radicality of the procedure. Thus, the use of
      immunoscintimetry is helpful in early decision making on adjuvant treatment
      modalities.

PMID- 7724368
TI  - Body blow. Interview by Jane Cassidy.

PMID- 7724369
TI  - Admirable service. Interview by Lynn Eaton.

PMID- 7724370
TI  - Pay campaign. Natural-born militants?

PMID- 7724371
TI  - Pay campaign. Strike ethic. Interview by Janet Snell.

PMID- 7724372
TI  - Nursing input in Ilizarov fixation.

PMID- 7724373
TI  - Orthopaedics. Information as and when required.

PMID- 7724374
TI  - Specialist services for people with learning disabilities.
AB  - Research confirms that the needs of people with learning disabilities are often
      missed out of health promotion. This paper reports the results of health
      screening clinics run for people with learning disabilities.

PMID- 7724375
TI  - Use of anticoagulants in hospital and community.
AB  - Drugs affecting haemostasis can be divided into three main groups depending on
      which component of haemostasis they affect: coagulation, fibrinolysis or platelet
      activity. This paper looks at the anticoagulant group of drugs, the main
      compounds in present use, the indications for use, potential side-effects and the
      implications for nurses when providing patient care.

PMID- 7724376
TI  - The use of magnetic resonance imaging in diagnosis.
AB  - Until recently diagnostic radiology has been restricted to X-ray, computerised
      tomography (CT) and ultrasound. These techniques exploit the absorption of
      reflection of waves passed into or through the body. Magnetic resonance imaging
      (MRI) actually stimulates the body to produce a signal itself.

PMID- 7724377
TI  - Reasons for older people attending A&E.
AB  - This study aimed to identify any shortfalls in the discharge of older people from
      an A&E departments and areas in which improvements could be made. The findings
      highlighted the fact that more than 40% of the attendances to A&E did not require
      urgent treatment and that nearly 59% of attenders lived alone. The terms
      'justifiable' and 'unjustifiable', applied to attendances in the study group, are
      used in the paper to differentiate between cases where immediate attention was
      required and where it was not. This judgement was based on the author's
      professional knowledge (see discussion section).

PMID- 7724378
TI  - Accuracy in ward-based blood glucose monitoring.

PMID- 7724379
TI  - Happy babies.

PMID- 7724380
TI  - Speaking up for others.

PMID- 7724381
TI  - Capital care.

PMID- 7724382
TI  - Body politic. Outlook murky.

PMID- 7724384
TI  - Cardiostim '94. Proceedings. Nice, June 15-18, 1994.

PMID- 7724383
TI  - Homoeopathy: first aid treatments.

PMID- 7724385
TI  - Epicardial and nonthoracotomy defibrillation lead systems combined with a
      cardioverter defibrillator.
AB  - The intraoperative and long-term results were reviewed in 67 patients who
      underwent implantation of the Ventritex Cadence defibrillator with either
      epicardial patch (EPI, 25 patients) or nonthoracotomy CPI Endotak (ENDO, 42
      patients) defibrillation lead systems. In the ENDO group, 35 patients (83%) had a
      defibrillation threshold (DFT) of < or = 20 joules and did not require a
      subcutaneous patch. Intraoperatively, the DFT was 13 +/- 9 joules (mean +/- SD)
      for EPI and 15 +/- 8 joules for ENDO (P = NS). There was no perioperative death
      in either group. During a mean follow-up of 12 +/- 8 months, there was no sudden
      death, and four patients died from congestive heart failure (3 EPI, 1 ENDO).
      During follow-up, 875 spontaneous arrhythmia episodes (AE) occurred in 15 of 25
      EPI patients (60%), versus 652 in 28 of 42 ENDO patients (67%; P = NS).
      Ventricular tachycardia at a rate > or = 222 beats/min or ventricular
      fibrillation represented 167 AE for EPI (19%) and 182 AE for ENDO (28%), and was
      terminated by the first shock in 76% and 75% of attempts, respectively.
      Ventricular tachycardia at a rate < 222 beats/min represented a total of 1,178 AE
      and antitachycardia pacing was successful in 660 of 708 AE (93%) with EPI and 414
      of 470 AE (88%) with ENDO lead systems (P = NS). Therefore, a nonthoracotomy
      approach using the Cadence V-100 is safe and effective and has clinical results
      that are not significantly different from epicardial defibrillation lead systems.

PMID- 7724386
TI  - Results of delivered therapy for VT or VF in patients with third-generation
      implantable cardioverter defibrillators.
AB  - Third-generation implantable cardioverter defibrillators (ICDs) offer tiered
      therapy and can provide significant advantage in the management of patients with
      life-threatening arrhythmias. Three different types of ICDs were implanted in 21
      patients with ventricular tachycardia (VT) or ventricular fibrillation (VF).
      Arrhythmia presentation was VT (76%), VF (10%), or both (14%). The mean left
      ventricular ejection fraction for the group was 32.4 +/- 7%. No surgical
      mortality occurred. Prior to discharge individual EPS determined the final
      programmed settings of the ICDs. During a mean follow-up of 13 +/- 1.4 months
      (range 2-20) the overall patient survival was 85.7%. No sudden arrhythmic or
      cardiac death occurred. Twenty of 21 patients (95%) received therapy by their
      device. In 14 patients (67%) antitachycardia pacing (ATP) was programmed "on," 13
      of which was self-adaptative autodecremental mode. There were 247 VT episodes,
      231 of which were subjected to ATP with 97% success and 3% acceleration or
      failure. Low energy shocks reverted all other VT episodes. VF episodes were
      successfully reverted by a single shock (93%), two shocks (6%), or three shocks
      (1%). We conclude that ATP therapy of VT is successful in the large majority of
      episodes with rare failures, and that VF episodes are generally terminated by a
      single ICD shock.

PMID- 7724387
TI  - Safety of antitachycardia pacing in patients with implantable cardioverter
      defibrillators and severely depressed left ventricular function.
AB  - The purpose of this study was to investigate the efficacy and safety of
      antitachycardia pacing (ATP) in third-generation implantable cardioverter
      defibrillators (ICDs) for terminating spontaneously occurring ventricular
      tachycardias (VTs) in patients with severely depressed left ventricular (LV)
      function. Ninety-one patients with active ATP were followed for 16 +/- 13 months.
      During this period, 775 VT episodes occurring in 36 patients were treated by ATP.
      The patients were divided into two groups according to their LV ejection fraction
      (LVEF): group A with LVEF < or = 30% (n = 20), and group B with LVEF > 30% (n =
      16). There were no differences between both groups in age, gender, underlying
      heart disease, indication for ICD therapy, or drug therapy. The VT rates were
      comparable (group A: 183 +/- 16 beats/min; group B: 180 +/- 21 beats/min; P =
      NS). Eighty-three percent of all episodes (n = 332) in group A and 93% of the VTs
      (n = 443) in group B were ATP terminated (P < 0.01). Ten percent of VTs in group
      A were accelerated by ATP into the ventricular fibrillation zone versus 2% in
      group B (P < 0.01). The individual termination rate and acceleration rate per
      patient were comparable in both groups. All VT episodes unresponsive to ATP were
      converted by backup shocks. The efficacy of first-shock therapy was similar in
      both groups (group A: 89%; group B: 97%; P = NS). The proportion of patients who
      needed at least one backup shock for unsuccessful ATP was comparable in both
      groups (group A: 65%; group B: 56%; P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724388
TI  - AICD automatic cardioverter defibrillator clinical update: 14 years experience in
      over 34,000 patients.

PMID- 7724389
TI  - Management of electrical instability after ICD implantation.
AB  - Postoperative ventricular arrhythmias were studied in 52 patients receiving
      implantable cardioverter defibrillators (ICDs). A group of 9 patients was
      identified who experienced electrical instability (EI). The lead approach was
      thoracotomy in 6 and nonthoracotomy in 3 patients. In 8 of 9 patients VTs started
      soon after surgery. There was no evidence of ischemia, cardiac failure,
      electrolyte imbalance, or drug intoxication. The severity of ventricular
      arrhythmias varied from a considerable increase in incidence of well-tolerated
      VTs in 3 patients (1 incessant) to poorly tolerated frequent VTs in 6 patients (2
      incessant). In 4 patients VTs led to cardiac failure. Ventricular arrhythmias
      during EI were refractory to antiarrhythmic drugs (AAD) in 7 of 9 patients. In 3
      patients VTs accelerated into fast VT or VF with antitachycardia pacing (ATP) or
      cardioversion. The successful management of EI was: sedation in 4 patients (3
      with midazolam 1 with temazepam), ATP and AAD in 2 patients, AAD and hemodynamic
      support in 2 patients, spontaneous resolution in 1 patient. All patients survived
      the period of postoperative EI. Two patients had a relapse of EI at 2- and 9
      months postimplantation, respectively, one of whom eventually died. CONCLUSIONS:
      EI occurred in 17% of patients after ICD implantation, had a varying degree of
      severity and required an individualized approach. Control of EI with AAD was
      successful in only 2 of 9 patients. Sedation with midazolam was useful in the
      management of EI.

PMID- 7724390
TI  - Sudden death and staged therapy for hemodynamic stabilization in patients
      enrolled in a heart transplantation program.
AB  - To investigate the impact of staged therapy for advanced heart failure on
      therapeutic endpoints, 236 consecutive patients (coronary artery disease/dilated
      cardiomyopathy in 61/175 patients, left ventricular ejection fraction 14% +/- 5%,
      New York Heart Association Class II/III/IV in 102/79/55 patients, respectively)
      with advanced heart failure were prospectively followed. One hundred thirty-seven
      patients enrolled from January 1989 to December 1991 were treated conventionally
      with digoxin, furosemide, and low dose angiotension converting enzyme (ACE)
      inhibition. Patients refractory to this therapy underwent urgent heart
      transplantation. Ninety-nine patients enrolled from January 1992 to August 1993
      underwent staged therapy: stage 1: maximal tolerated ACE inhibition; stage 2:
      therapy with PGE1 for pre- and afterload reduction to achieve hemodynamic
      stabilization; or stage 3: refractory patients bridged to heart transplantation
      with continuous outpatient dobutamine. Sudden death was defined as death within 1
      hour of symptoms if heart failure symptoms remained stable over the previous 7
      days. Conventionally treated patients were followed for 10 +/- 9 months; patients
      who underwent staged therapy for 9 +/- 5 months. In the group of patients that
      underwent standard therapy, 39 of 137 (28%) patients died: 5 (13%) deaths
      occurred suddenly, and death due to progressive pump failure occurred in the
      remaining 34 (87%) patients. In the group of patients that underwent staged
      therapy, 25 of 99 (25%) patients died: 13 (52%) deaths occurred suddenly, and 12
      (48%) deaths occurred due to progressive pump failure.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7724391
TI  - Subpectoral implantation of ICD generators: long-term follow-up.
AB  - A nonthoracotomy surgical approach using an endocardial electrode and combined
      implantation of a subcutaneous patch and the implantable cardioverter
      defibrillator (ICD) generator in a subpectoral pocket has been described. We
      report the long-term follow-up results in patients undergoing implantation using
      this approach. The patient population consisted of 28 patients (22 men and 6
      women) with a mean age of 59 +/- 12 years. The underlying heart disease consisted
      of coronary artery disease in 20 patients and dilated cardiomyopathy in 8
      patients. Sustained ventricular tachycardia was the mode of presentation in 16
      patients and sudden cardiac death in 12 patients. The mean left ventricular
      ejection fraction was 31% +/- 6%. The lead system consisted of an 8 French
      bipolar passive fixation rate sensing lead positioned at the right ventricular
      apex, an 11 French spring coil electrode positioned at the superior vena cava
      right atrial junction (surface area 700 mm2), and submuscular placement of a
      large patch (surface area 28 cm2) on the anterolateral chest wall near the
      cardiac apex via a submammary incision. A defibrillation threshold of < or = 15
      joules (J) was required for implantation. This criterion was not satisfied in
      five patients; thus, a limited thoracotomy was performed via the submammary
      incision, and the large patch was placed epicardially. The mean R wave amplitude
      was 12 +/- 3 mV, the mean pacing threshold was 1.0 +/- 0.5 V at 0.5 msec, and the
      mean defibrillation threshold was 12.6 +/- 3 J. ICD generators implanted were the
      Ventak-P in 17, PCD-7217 in 5, and the Cadence V-100 in 6 patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7724392
TI  - Initial clinical experience with a dual lead endocardial defibrillation system
      with atrial pace/sense capability. United States and Canada Enguard
      Investigations.
AB  - Ninety-three patients underwent implants of the Telectronics Model 4211 ICD
      attached to the Enguard PFX endocardial defibrillation lead system. Eighty-one
      males and 12 females ranging in age from 25-85 years (mean = 64). Coronary
      disease was the substrate in the majority (88%); mean left ventricular ejection
      fraction was 30%. VT was present in 66%, VF in 22%, and both in 7%. Three lead
      configurations were used in the study: ventriculo-atrial (U1, 86%); bidirectional
      (B2, 12%); and ventricular to patch (U2, 2%). Mean RV pacing thresholds were 0.46
      V pre- and 0.54 V posttesting, with no significant differences between the two.
      Mean R wave voltage was 11.05 mV pre- and 11.72 mV posttesting, also not
      significantly different. A subgroup of 13 patients had mean atrial pacing
      thresholds of 0.59 V at 0.5 msec pulse width, with mean P waves of 4.01 mV. Mean
      defibrillation threshold for the entire group was 10.6 J using biphasic
      waveforms. Defibrillation thresholds by configuration were: 399 V (U1); 475 V
      (U2); and 350 V (B2). All patients but one had thresholds < 550 V in at least one
      configuration. The 4211/Enguard system was implanted without (86%) or with (14%)
      a subcutaneous patch electrode. Early postoperative findings related to the ICD
      system include: one device circuit failure, one early lead dislodgement, and one
      pacing exist block.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724393
TI  - Cost and length of hospital stay: comparisons between nonthoracotomy and
      epicardial techniques in patients receiving implantable cardioverter
      defibrillators.
AB  - Twenty-five patients with implantable cardioverter defibrillators (ICDs)
      implanted intrathoracically (group I) were compared with 25 patients who
      underwent implant using the nonthoracotomy approach (group II). All systems were
      implanted by the same medical team, in the same high volume implanting center.
      Indications for implantation were comparable in both groups. Patient
      characteristics were not statistically different with the exception of age (66
      group I vs 71-group II; P < 0.05). Although left ventricular ejection fractions
      appeared to differ (32% vs 37%, respectively), this difference was not
      statistically significant (P = 0.06). ICD models used in group I were: Ventritex
      Cadence (16), Telectronics Guardian 4211 (2), Medtronic PCD (7); in group II they
      were: Ventritex Cadence (15), Guardian 4211 (2), and CPI 1600 (1). Total length
      of hospital stay was 16 +/- 6 days for group I versus 12 +/- 5 for group II (P <
      0.05). Number of postoperative days in an intensive care unit was 3.2 +/- 2.8 for
      group I versus 0.5 +/- 0.6 for group II (P < 0.0001). Postoperative length of
      stay was 8.2 +/- 3.1 for group I versus 5.7 +/- 4.4 for group II (P < 0.001).
      Mean total hospital charges for the entire length of stay were $72,918 +/-
      $26,770 in group I versus $55,031 +/- $42,870 in group II, representing a mean
      reduction of 21% in global costs for group II patients. These data confirm that
      nonthoracotomy ICD implantation in an experienced center is associated with
      significantly shorter hospital stays, a virtual elimination of the need for
      postoperative intensive care, and globally lower total hospital costs. In
      addition, the presence of a statistically older population in group II does not
      negate these beneficial effects.

PMID- 7724394
TI  - Low incidence of lead related complications associated with nonthoracotomy
      implantable cardioverter defibrillator systems.
AB  - Implantable cardioverter defibrillators (ICDs) are increasingly being implanted
      without the need for thoracotomy. Long-term lead performance and stability were
      evaluated in 150 consecutive patients in whom 1 of 3 nonthoracotomy ICD lead
      systems was implanted over a 3-year period from September 1990. RESULTS: Twelve
      (8%) patients (7 males, 5 females) experienced 13 lead complications during a
      follow-up period of 12 +/- 10 months. Complications were related to intracardiac
      leads in 7 (4 dislodgments, 2 fractures, 1 right ventricular perforation) and
      patch leads in 6 (2 folding, 1 fracture, 1 erosion, and 2 hematomas) cases.
      Freedom from lead related complications at 1 year was 92% (95% confidence
      interval, 86%-95%). A significant difference in freedom from lead complications
      between the two most frequently implanted lead systems was observed (P = 0.02).
      Complication rates were similar in the initial 75 and the more recent 75 implants
      (P = 0.5). The median time between lead implant and detection of complications
      was 37 days (range 3-1,147). Complications were diagnosed before hospital
      discharge in only two cases. In five patients, complications were asymptomatic
      and in three of these, reoperation was required due to inadequate defibrillation
      thresholds. Reoperation was necessary in 9 of 12 patients. CONCLUSIONS:
      Nonthoracotomy ICD lead systems are associated with a low complication rate.
      Complications may or may not cause symptoms, usually occur after hospital
      discharge, and require reoperation. Complications are not related to a "learning
      curve." There is a significant difference in performance between different lead
      systems.

PMID- 7724395
TI  - Alternative lead positioning in the right ventricular outflow tract in
      transvenous implantation of ICDs.
AB  - Pacing and sensing failure in apical right ventricular coil electrode PCD
      implantation due to ventricular scars or aneurysma may force the implanting
      surgeon to switch to more invasive procedures such as subxyphoidal pericardiotomy
      or thoracotomy for epimyocardial corkscrew electrode and for epicardial patch
      application. In order to avoid this more invasive operation in the most severely
      impaired patients, right ventricular outflow tract positioning of the RV
      electrode is suggested as an alternative RV electrode site for implantation. A
      study of four cases shows that this occasional procedure is a practicable method
      to avoid more invasive techniques. Excellent pacing, sensing, and defibrillation
      characteristics were obtained and application is relatively simple.

PMID- 7724396
TI  - Effect of implantable nonthoracotomy defibrillation system on permanent
      pacemakers: an in vitro analysis with clinical implications.
AB  - Implantable cardioverter defibrillation systems are capable of delivering over
      700 volts, and upwards of 40 joules (J) directly to the heart. Nonthoracotomy
      lead (NTL) systems allow the delivery of this energy to the inside of the heart,
      and potentially in close proximity to the leads of an endocardial pacing system.
      The effect of repeated maximal energy discharges (stored energy 40 J, delivered
      energy 38 J), utilizing both monophasic as well as biphasic shock pulses
      delivered via two different configuration NTL systems on a series of Pacesetter
      polarity programmable present generation single, and dual chamber pacemakers was
      evaluated in vitro using a saline test tank. All pulse generators studied
      demonstrated normal function and were not reprogrammed nor adversely affected by
      repeated defibrillation shocks. The current induced in the leads was assessed,
      and shown to be as high as 1.5 amps in the proximal conductor and 1.2 amps in the
      distal conductor of the ventricular lead, which may cause damage at the electrode
      myocardial interface, and explain some of the postshock rise in capture and
      sensing thresholds that have been reported with implanted pacing systems
      postdefibrillation.

PMID- 7724397
TI  - Effects of internal defibrillation on an implanted pacing system with
      programmable polarity.
AB  - Management of multiple cardiac arrhythmias in some patients with both an
      implantable cardioverter defibrillator (ICD) and a pacemaker has demonstrated
      several advantages. In such circumstances, it is imperative that pacemaker
      function and its programmed parameters be preserved following a defibrillation
      shock. This article describes the effects encountered by a specific programmable
      polarity pacemaker (RelayR 294-03) when subjected to electrical defibrillation in
      a canine model. Three pacemakers were repeatedly tested in three separate dog
      experiments. Each pacemaker, with its leads implanted in the right atrium and the
      right ventricle, was subjected to a minimum total number of 24 high energy
      biphasic and monophasic shocks (600-700 V) delivered by a coexisting ICD system
      using three different defibrillating lead configurations. None of the pacemaker
      systems showed any failure in function; all pacemakers continued to function
      within preshock specification and conversion to unipolar pacing and/or backup
      mode was not observed in any of the tests. Intracardiac electrical potentials
      measured directly off the ICD and the pacemaker leads, during a defibrillation
      shock (mean 566.6 V; 23.7 J), showed that potentials measured in a bipolar
      configuration (tip-ring: mean 21.0 V in atrium, 12.0 V in ventricle) were
      significantly less than potentials measured in a unipolar configuration (tip-can:
      mean 387.9 V in atrium, 394.0 V in ventricle; ring-can: mean 405.6 V in atrium,
      395.4 V in ventricle). Our compatibility tests demonstrate that use of this
      programmable-polarity pacemaker in concert with an ICD system appears to be safe.
      Testing similar to the present study should be conducted prior to complete
      clinical acceptance of combined ICD and pacemaker implantation.

PMID- 7724398
TI  - Transthoracic DC shock may represent a serious hazard in pacemaker dependent
      patients.
AB  - External defibrillation is widely used for the termination of various atrial and
      ventricular tachyarrhythmias, including pacemaker patients. Our study was
      intended to evaluate the effects of DC shocks in 36 patients with unipolar
      pacemakers implanted in the right pectoral region (25 DDD, 10 VVI, 3 AAI). The
      shocks were delivered with paddles on the anterior surface of the thorax, as far
      as possible away from the pacemaker. The pacing output was programmed at 0.5 msec
      and 5 V (25 patients), 4 V (1 patient), and 2.5 V (10 patients). Transient loss
      of capture occurred in 18 patients (50%). These patients, compared with those
      without capture failure, received higher peak and cumulative shock energies,
      respectively, 216 +/- 99 versus 123 +/- 50 joules (P < 0.002) and 352 +/- 62
      versus 147 +/- 98 joules (P < 0.004) and had a lower pacemaker pulse amplitude
      (4.0 +/- 1.2 vs 4.6 +/- 1.0 V, P = 0.11). Failure to capture lasted from 5
      seconds to 30 minutes (mean 157 sec). In 15 patients the ventricular stimulation
      threshold was measured before and serially after cardioversion. A six-fold
      threshold increase was observed 3 minutes after the shock (P < 0.004) with
      gradual recovery to nearly baseline values at 24 hours. Transient sensing failure
      occurred in 7 of the 17 patients in whom it could be evaluated (41%).
      Furthermore, three cases of shock induced pacemaker malfunctions were observed
      requiring replacement of the stimulator in two patients. In conclusion, the
      incidence of loss of capture in pacemaker patients subjected to electrical
      cardioversion/defibrillation is high.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724399
TI  - Implantable defibrillation and thromboembolic events.
AB  - In ICD patients thromboembolic events (TEEs) are described as possible
      complications at implant or during the follow-up. We report four cases of TEEs
      (two peripheral and two cerebral; 6.5% of patients) that occurred in our series
      during a mean follow-up of 19.4 months. The patients had chronic postinfarction
      LV aneurysm (3) and idiopathic dilated cardiomyopathy (1). None had previous
      embolisms nor evidence of left atrial or LV clots at standard preoperative
      transthoracic echocardiography. No paroxysms of atrial fibrillation were
      documented prior or after ICD implant. We discuss the possible causes of
      embolization and the suitability of anticoagulant therapy in ICD patients.

PMID- 7724400
TI  - Large capacitor defibrillation waveform reduces peak voltages without increasing
      energies.
AB  - This study tested the hypothesis that increasing capacitance would allow a
      reduction in ICD size without reducing the deliverable energy. For example, the
      volume of a single 450 microF capacitor (390 V peak) is 1/3 less than that of two
      250 microF capacitors (780 V), but it can store equivalent amounts of energy.
      METHODS: Endocardial defibrillation electrodes (3.4 cm) were positioned in the RV
      apex and at the RA/SVC junction in six mixed-breed, isoflurane anesthetized pigs
      (41 +/- 3 kg). Three 17-cm ribbon wires were positioned subcutaneously on the
      left lateral chest (SQArray). Two CPI VENTAK ECDs were equipped to deliver 60/40
      biphasic waveforms using either 125 microF (STD) or 500 microF (LD) of
      capacitance. A 15 shock up/down protocol was used to determine the 50%
      probability of success levels for each waveform in each animal. Shocks were
      delivered from RV(-)-->SVC + SQArray(+) in random order. Results were compared
      using paired Student's t-tests and are reported as mean +/- SE. RESULTS: The 500
      microF, long duration waveform reduced peak voltage 41% (374 +/- 18 V [STD] vs
      219 +/- 14 V [LD], P < 0.001) and reduced peak current 38% (11.0 +/- 1.1 A [STD]
      vs 6.8 +/- 0.6 A [LD], P < 0.001) but did not significantly change the delivered
      energy (12.4 +/- 1.3 J [STD] vs 13.4 +/- 1.0 J [LD]). Durations increased from
      10.0 +/- 0.2 to 17.6 +/- 0.5 msec (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724401
TI  - Analog-digital recording of current and voltage during high voltage DC shocks.
AB  - Efficient on-line digitization is the prerequisite for computerized analysis of
      the electrical phenomena occurring during defibrillation. Conventional hardware
      presently provides only limited time resolution. The performance of various
      digitization rates for recording of voltage, current, and calculation of derived
      quantities like impedance, energy, and defibrillator capacitance was
      investigated. It was assessed both experimentally and by computer simulation of a
      trapezoidal discharge (of 9 msec duration into a constant resistive load of 50
      omega with a defibrillator capacitance of 132 microF). The accuracy achieved with
      different digitization rates is given. For example, an accuracy of 1% for analog
      digital conversion for impedance calculation during this kind of DC shock
      requires a sampling rate of 8 kHz without, and a rate of 1 kHz with linear
      interpolation to correct for the hardware dependent error due to sequential
      sampling. CONCLUSION: Highly efficient analog-digital conversion of delivered
      voltage and current during DC shocks is available within the limits of
      conventional inexpensive hardware.

PMID- 7724402
TI  - Low voltage shocks have a significantly higher tilt of the internal electric
      field than do high voltage shocks.
AB  - Typically, an implantable cardioverter defibrillator (ICD) uses a cardioversion
      shock that is a lower voltage pulse of the same morphology and tilt as its
      defibrillation pulse. We investigated the internal electric field resulting from
      an ICD low voltage shock to determine whether its field characteristics matched
      those of the internal electric field of a high voltage shock. We attached
      epicardial patch electrodes, for shock delivery, to five fresh pig hearts placed
      in a diluted, heparinized saline bath. We inserted two plunge electrodes into the
      myocardium to measure an internal voltage proportional to the electric field.
      Monophasic 20-msec shocks, from a 140-microF capacitor, ranging from 0.1-30
      joules, were delivered through the patches. We measured the current, external
      voltage, and internal voltage every 0.1 msec throughout the duration of a shock.
      For each shock, we calculated the time point that represented the 65% tilt
      position as measured across the patch electrodes. At this 65% tilt time position,
      we measured the pulse widths and calculated the internal tilt from the internal
      voltage. We found that the initial internal voltage for the 30-joule shock was
      173 +/- 40 volts compared to 10 +/- 2 volts for the 0.1-joule shock. Similarly,
      we found that the final internal voltage for the 30-joule shock was 56 +/- 14
      volts compared to 2 +/- 1 volts for the 0.1-joule shock. Thus, the internal tilt
      for the 30-joule shock was 68 +/- 1% versus 82 +/- 3% for the 0.1-joule shock (P
      < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724403
TI  - A long thin electrode is equivalent to a short thick electrode for defibrillation
      in the right ventricle.
AB  - We hypothesized that a long thin right ventricular (RV) electrode would have
      equivalent defibrillation threshold (DFT) performance to a short thick electrode
      with approximately the same surface area. This could lead to thinner transvenous
      lead systems, which would be easier to implant. A thin (5.1 French) lead was
      compared to a standard control (10.7 French). The thin lead had an 8-cm RV
      electrode length with a surface area of 4.26 cm2. The standard lead had a RV
      electrode length of 3.7 cm and a surface area of 4.12 cm2. A 140-mu French
      capacitor 65%/65% tilt biphasic defibrillation shock was delivered between the RV
      electrode and a 14-cm2 subcutaneous patch. DFTs were determined following 10
      seconds of fibrillation in 11 dogs by a triple determination averaging technique.
      The thin lead had a lower resistance (77.1 +/- 27.4 omega vs 88.9 +/- 30.3 omega,
      P < 0.001) than did the thick lead. There was no significant difference in stored
      energy DFTs (9.9 +/- 2.5 vs 10.3 +/- 2.7, P = 0.098 2-sided, P = 0.049 1- sided).
      This was in spite of the fact that the long thin lead had a portion of its RV
      coil extending above the tricuspid valve and, thus, not contributing efficiently
      to the ventricular gradients in the small dog heart. We conclude that a long thin
      right ventricular electrode and a standard short thick electrode had equivalent
      defibrillation performance. This preliminary result should be confirmed in
      clinical studies as it could lead to significantly thinner transvenous lead
      systems.

PMID- 7724404
TI  - Woven wire patches are superior to solid disks for subcutaneous electrodes:
      implications for active can defibrillation.
AB  - The housing of the implantable cardioverter defibrillator (ICD) is being
      considered for a remote electrode to replace the conventional subcutaneous woven
      wire patch. It is not clear that the solid smooth and rigid metal surface of the
      ICD housing will provide the same performance as does the woven wire patch. We
      compared a solid titanium disk to a titanium woven wire patch for defibrillation
      performance in a canine model. The patch had a smaller outline area, a slightly
      smaller conductive perimeter, and slightly less of a small feature surface area
      than did the disk. The remote electrode (disk or patch) was inserted at the point
      of maximal apical cardiac impulse. A commercially available endocardial electrode
      was placed in the right ventricle (RV). Conventional biphasic shocks (140
      microFrench capacitor and 65% tilt) were delivered between the RV and
      subcutaneous electrode. The patch had significantly lower resistances than did
      the disk (81.6 +/- 8.0 omega vs 90.0 +/- 11.6 omega P < 0.006). The patch also
      had significantly lower stored energy defibrillation thresholds than did the disk
      (8.0 +/- 2.6 J vs 9.3 +/- 3.3 J, P < 0.007). In spite of smaller values for every
      geometrical dimension, the woven wire patch out performed the solid disk for
      defibrillation with conventional biphasic waveforms. Since the ICD housing is
      typically smooth titanium, the use of waveforms better suited for the active can
      configuration may deserve a systematic evaluation.

PMID- 7724405
TI  - Transseptal defibrillation is superior for transvenous defibrillation.
AB  - The conventional electrode configuration of current internal defibrillation
      systems most commonly use superior vena caval (SVC) or combined SVC and
      subcutaneous (SC) electrodes as anode, and right ventricular apex (RVA) electrode
      as cathode. We have demonstrated earlier that the septal mass is important for
      defibrillation. The purpose of the present study was to compare a transseptal to
      a conventional electrode arrangement in the canine model. Three endocardial
      electrodes, 5 French EnGuard were positioned in RVA, SVC, and the right
      ventricular outflow (RVO) in eight dogs. A 5 French SC electrode was positioned
      in the fifth left intercostal space. RVA-RVO-/SC+ (configuration 2) was compared
      to SVC-SC+/RVA- (configuration 1). Defibrillation threshold testing was performed
      using asymmetrical biphasic shock, 6 msec+/2 msec-. Probit fit was used to
      compare the results at 40%, 50%, 60%, and 90% probabilities, and the logistic
      regression analysis to estimate the impact of variables. Electrode configuration
      had the strongest predictive value. Configuration 2 was superior to configuration
      1 (P = 0.0016). At any voltage settings the probability of success for
      configuration 2 was greater, and current less (P < 0.00005). The energy
      requirements were reduced by approximately 33% for configuration 2. There were no
      significant differences in impedance between the two configurations. We conclude
      that transseptal defibrillation is more effective because of the improved lead
      geometry and voltage gradient.

PMID- 7724406
TI  - Electrode surface area is an important variable for defibrillation.
AB  - Previous studies have established efficacy of transseptal defibrillation. The
      purpose of the present study was to evaluate the role of transvenous electrode
      surface area for defibrillation. Sixteen dogs were randomized to 8 French and 5
      French EnGuard electrodes; 8 dogs in each group. The length of the defibrillation
      coils was identical for both, but the surface area was different due to
      differences in the electrode diameters. Defibrillation threshold (DFT) testing
      was performed using a biphasic shock waveform, 6 msec+/2msec-. Logistic
      regression analysis was used to determine if the probability of defibrillation
      adjusted for voltage, current, and energy was different for 8 French electrodes.
      Logistic regression analysis found significant differences between 8 French and 5
      French electrodes, with less voltage (P < 0.005), current (P < 0.03), and energy
      (P < 0.001) required at any level of probability to defibrillate for 8 French
      electrodes. These results support the conclusion that the surface area for
      endocardial electrodes is a significant factor for defibrillation. Therefore,
      when designing endocardial electrodes a desirable objective of reducing the
      electrode size should be weighed against the need to minimize DFTs.

PMID- 7724407
TI  - TiN: a suitable coating for defibrillator electrodes?
AB  - The electrochemical behavior of porous TiN coating for defibrillator electrodes
      was investigated by in vitro studies. A commercially available Ti patch was
      compared with a Ti patch coated with a layer of porous TiN. Similarly, the
      influence of the TiN coating on a Pt/Ir intracardial electrode was tested. Porous
      TiN coatings were made by reactive sputtering on the plain electrodes. Electrode
      potential measurements were performed during monophasic anodic and cathodic
      defibrillator shocks delivering energies between 1 J and 49 J. Porous TiN coating
      of Pt/Ir coils was found suitable to deliver cathodal pulses, while a plain coil
      remains recommended for anodic shocks. TiN coating was of benefit for
      conventional Ti patches. Particularly, in the case of anodic shocks, the TiN
      layer protected the Ti-mesh from immediate oxidation. However, above 70 anodic
      shocks of 49 J, the TiN coating underwent oxidation to an oxynitride. An
      estimated 180 anodic shocks of 10 J could be delivered before TiN oxidation
      became measurable by increased polarization.

PMID- 7724408
TI  - Mother-to-infant HIV transmission: timing, risk factors and prevention.
AB  - Identifying when--during pregnancy, delivery or the postnatal period-
      transmission of human immunodeficiency virus (HIV) from mother to infant usually
      takes place is critical to the development of methods to prevent maternal-infant
      transmission. Evidence is reviewed in this paper as to whether transmission
      occurs prepartum (early or late in gestation), intrapartum, or postpartum with
      breast feeding. Evidence in support of the notion of prepartum transmission has
      come from isolation of HIV from aborted fetal organs, comparison of maternal
      child viral genotypes and study of neonatal cell-mediated immune responses.
      Evidence against prepartum transmission is that fewer than half of the children
      later known to be HIV-infected can be identified by virological tests carried out
      close to birth. A reduced rate of transmission in infants delivered by Caesarean
      section, and a reduced risk of transmission to second-born twins delivered
      vaginally, offers support to the view that intrapartum factors influence the risk
      of HIV transmission. Transmission through breast feeding can occur if a mother is
      infected postpartum and seems to pose some additional risk if she is already
      infected at parturition. The risk of infection increases with the stage of
      maternal HIV disease, but specific immunological, clinical and viral
      characteristics need to be investigated further. A clinical trial of zidovudine,
      used during late pregnancy and delivery and given to the infant at birth, has
      reported a significant reduction in transmission. Primary prevention of HIV
      infection in women remains a principal priority.

PMID- 7724409
TI  - Abstinence from alcohol before pregnancy and reproductive outcome.

PMID- 7724411
TI  - Fumes from the spleen.

PMID- 7724410
TI  - Enrolment into Birth to Ten (BTT): population and sample characteristics.
AB  - The population under study in the South African longitudinal study of urban
      children and their families, 'Birth to Ten' (BTT), comprised all births during a
      7-week period from April to June 1990 in Soweto-Johannesburg. Specification of
      the population base for the cohort was hampered by a number of flaws in the
      notification and record-keeping systems of the local authorities. As far as could
      be ascertained, 5460 singleton births occurred during this time to women who gave
      a permanent address within the defined region. Enrolment into BTT took place over
      the first 15 months of the study and covered the antenatal, delivery, 6-month and
      1-year periods. By the end of this time, and despite a major health service
      strike during the delivery phase, 74% of all births (4029 cases) had been
      enrolled into the study. There were marked variations in levels of enrolment,
      however, by population group membership, residential area and place of delivery.
      In general, there was substantial under-enrolment of largely middle-class white
      women and their babies. Initial non-enrolment of specific segments of the
      population and attrition of the enrolled sample up to the end of the first year
      are discussed in the context of racial and social differentiation in South
      Africa.

PMID- 7724412
TI  - Violence, pregnancy and birth outcome in Appalachia.
AB  - Few studies have followed pregnant women prospectively to examine the impact of
      violence on birth outcome. We included such an assessment in a prospective study
      of pregnancy among low-income women. Nurses and social workers interviewed
      pregnant women (n = 364) and asked if they had been the object of violence since
      they became pregnant. These prenatal interviews were linked with information from
      perinatal records and with birth and death information. In total, 15.9% of women
      in the study indicated they had been abused since they became pregnant. Abused
      women were more likely to be teenagers and to have partners who were teenagers.
      Abused women were more likely to be primiparous, to smoke during pregnancy and to
      have physical problems related to stress. Women battered during pregnancy were
      more likely to suffer fetal distress or fetal death [Odds Ratio (OR) 3.68; 95%
      Confidence Interval (CI) 1.36, 9.94], even after adjusting for maternal age and
      smoking status. Finally the infants of abused women were more likely to remain in
      hospital after their mother's discharge (OR: 3.75; 95% CI: 1.38, 10.23). Our
      findings suggest that fetuses may be compromised in utero, as shown by higher
      rates of fetal distress and fetal death found among women physically abused
      during pregnancy.

PMID- 7724413
TI  - Reproductive history and the risk of neonatal sepsis.
AB  - It was recently suggested that a previous abortion increases the risk of
      intrapartum infection in a following pregnancy. The authors hypothesised that
      abortion also could be associated with a higher risk of neonatal sepsis. A case
      control study of neonatal sepsis was conducted using the Washington State Birth
      Registry. Cases of sepsis were selected among singleton livebirths during the
      period 1984-90, and compared with a control group for the occurrence of
      spontaneous or induced abortion in previous pregnancies. The risk estimates were
      calculated using a stratified analysis. After exclusion of primigravidae, the age
      adjusted odds ratio (OR) was 1.68, with a 95% confidence interval (CI) 1.33, 2.11
      for previous spontaneous abortion, and 2.20 (95% CI 1.73, 2.79) for induced
      abortion, compared with previous livebirth. After exclusion of nulliparous women,
      the OR decreased to 1.19 (95% CI 0.90, 1.58) for spontaneous abortion and 1.45
      (95% CI 1.03, 2.04) for induced abortion. After controlling for the effect of
      parity, induced abortion is associated with an increased risk of neonatal sepsis
      in a subsequent pregnancy, but the association between spontaneous abortion and
      sepsis is small and non-significant. The authors suggest that the procedures
      involved in a therapeutic abortion might produce a latent, sub-clinical infection
      that persists until the next pregnancy, and is then transmitted to the newborn.

PMID- 7724414
TI  - Similarities and disparities in maternal risk and birth outcomes of white and
      Japanese-American mothers.
AB  - This study compares the maternal sociodemographic and prenatal care
      characteristics and birth outcomes of US resident white and Japanese-American
      mothers, using data from the state of Hawaii. The specific focus is to determine
      to what extent these factors can explain variations in newborn maturity and
      mortality indicators. Single livebirths to resident, non-military dependent white
      and Japanese-American mothers were selected for analysis from the 1979-1990
      linked livebirth-infant death files from Hawaii. Compared with white mothers,
      Japanese-American mothers were significantly more likely to be married, age 18
      years and older, have higher educational attainment, and have adequate prenatal
      care utilisation. The majority of Japanese-American mothers were born in Hawaii,
      while the majority of white mothers were born on the US mainland. The mean
      birthweight of Japanese-American infants was 200 g lighter than that of white
      infants. Infant mortality rates (IMRs) for both groups were below the US Year
      2000 Health Objective. After controlling for maternal sociodemographic and
      prenatal care factors with logistic regression, Japanese-American infants had
      significantly higher risks of low birthweight, preterm and very preterm birth and
      of being small-for-gestational age. These findings indicate that populations with
      preferential maternal sociodemographic and prenatal care risk indicators may
      still exhibit higher low birthweight percentages, but achieve comparatively low
      IMRs.

PMID- 7724415
TI  - A multicentre study of perinatal mortality in Nepal.
AB  - A prospective survey was carried out in two Kathmandu hospitals and two rural
      districts to establish urban and rural perinatal mortality rates (PNMRs) for
      these four centres in Nepal and to ascertain the causes of perinatal mortality.
      All perinatal deaths occurring over a 1-year period in the four centres were
      included (during which time there was a total of 14,967 births). Cause of death
      was established by contemporary review of hospital case records or by structured
      questionnaire ('verbal autopsy') in the rural areas. The PNMRs in the hospitals
      were 48.0 and 23.7 per thousand total births respectively, whilst those of the
      rural settings were 96.2 and 42.5 per thousand births. Perinatal asphyxia, low
      birthweight and infection were the most common causes but many of the deaths were
      unexplained. The high mortality rates were felt to reflect the difficult
      circumstances of childbirth in Nepal. It was concluded that a number of
      interventions would appear appropriate, but that these should be introduced in a
      scientific manner.

PMID- 7724416
TI  - High incidence of congenital dislocation of the hip in Northern Ireland.
AB  - To determine the incidence of congenital hip dislocation (CDH) a retrospective
      study was carried out of cases occurring in a defined population using multiple
      information sources. Of 138,600 children born in the period 1983-1987, a total of
      243 were diagnosed with CDH, defined as those requiring splintage or surgery
      whose treatment extended beyond 6 months of age. Incidence and estimates of
      relative risks for pre-disposing factors were determined. The rate was 1.75 cases
      per 1000 livebirths. Major risk factors were female gender and breech
      presentation. The proportions of cases identified before 1, 3 and 6 months of age
      were 8, 14 and 35%, respectively. Despite using a restrictive definition, we have
      obtained an incidence rate among the highest reported in any United Kingdom
      population. Early detection is widely accepted as desirable, but neonatal
      screening has proved ineffective.

PMID- 7724417
TI  - Determination of intra- and inter-individual variability and its effect on the
      number of days required to assess the usual intake of a 1-year-old infant
      population.
AB  - Diet variability influences the accuracy of the assessment of the relationship
      between nutrient intake and disease. The present study investigates intra- and
      inter-individual variability in an infant population at 12 months. The mothers of
      79 infants completed a 7-day weighted food record. No significant difference in
      nutrient intake was observed between males and females. For some nutrients an
      intra-/inter-individual variability ratio > 1 was found. Adjustment for total
      calorie intake slightly altered the intra-/inter-individual variability ratio of
      many nutrients. An error margin of 10% or less for calories can be expected
      within an 18-day study. Most nutrients however would need to be studied for over
      30 days to give an error margin < or = 10%. For dietary cholesterol, vitamins A,
      B6, C, and E, bracketing the error within the 10% margin would require an
      unrealistic time frame. Adjustments for calorie intake reduced the number of days
      in the dietary record for some nutrients. A lower intra/inter-individual
      variability ratio was seen when data for adults and older infants were compared.

PMID- 7724418
TI  - A patient with co-existing bronchial carcinoid tumour and bilateral
      phaeochromocytoma.
AB  - We report a 31-year-old Chinese man with bronchial carcinoid tumour and bilateral
      phaeochromocytoma. His sister also gave a history of bilateral carotid body
      paraganglioma. This case demonstrates the importance of screening for other
      endocrine disorders in patients with foregut carcinoid tumours.

PMID- 7724419
TI  - Primary hyperaldosteronism due to an adrenal adenoma in a 14-year-old boy.
AB  - Conn's syndrome due to an adrenal adenoma is very rare in children. This paper
      reports a 14-year-old boy with primary hyperaldosteronism due to an adrenal
      adenoma. His biochemistry data were compatible with either bilateral adrenal
      hyperplasia or an adrenal adenoma. A dexamethasone test did not suppress
      aldosterone levels. Venous catheter sampling and 75Se-selenomethylcholesterol
      scanning suggested that the hyperaldosteronism originated at the right adrenal.
      Computed tomography showed an 8-mm low-density nodule in the right adrenal gland
      and magnetic resonance imaging confirmed the nodule which had high signal
      intensity on T2-weighted images consistent with a functioning adenoma. Surgery
      confirmed the right adrenal adenoma, and the patient was cured by right
      adrenalectomy. This case illustrates the difficulty of defining the aetiology of
      primary hyperaldosteronism and we review the biochemical and scanning techniques
      available to aid in diagnosis. Hypertension is unusual in children and endocrine
      causes are very rare, but Conn's syndrome should always be considered in the
      differential diagnosis.

PMID- 7724420
TI  - Renal failure due to cholesterol embolisation.

PMID- 7724421
TI  - Yellow nail syndrome and xanthogranulomatous pyelonephritis.
AB  - We report a case of a 74-year-old woman exhibiting the yellow nail syndrome in
      association with ipsilateral xanthogranulomatous pyelonephritis. Nephrectomy
      resulted in complete resolution of the pleural effusion and slow improvement of
      the yellow nails. This report calls attention to the renal-related pleural
      effusion, and to the thorough investigation needed for the yellow nail syndrome.

PMID- 7724422
TI  - Acute myelomonocytic leukaemia complicated by an acute aortic thrombosis.
AB  - Acute aortic thrombosis is a rare condition, occurring mainly as a result of
      trauma or atherosclerosis and occasionally secondary to hypercoagulable states.
      We report a patient with relapsed acute myeloid leukaemia who developed an
      unusual complication, acute aortic thrombosis.

PMID- 7724423
TI  - Streptokinase and facial haematoma.
AB  - We report two cases of facial haematoma following streptokinase therapy. This is
      an important complication as it can have fatal consequences. Early recognition
      and close monitoring are essential as emergency intervention may be required.

PMID- 7724424
TI  - Assessment of pancreatic duct damage following trauma: is endoscopic retrograde
      cholangiopancreatography the gold standard?
AB  - A 12-year-old girl was admitted as an emergency with blunt pancreatic trauma.
      Computed tomography (CT) showed an intact pancreas. She failed conservative
      treatment. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated
      division of the pancreatic duct at the neck of pancreas. At laparotomy, however,
      there was complete necrosis of the pancreatic head. She recovered well following
      enteric drainage of the body of pancreas. CT and ERCP are considered the optimal
      imaging for pancreatic trauma but the findings may be misleading.

PMID- 7724425
TI  - Endocarditis due to high-level gentamicin-resistant Enterococcus faecalis.
AB  - We report a case of aortic valve endocarditis caused by Enterococcus faecalis
      highly resistant to gentamicin, which failed to respond to conventional
      antibiotic combination therapy. Extensive in vitro testing was required to
      determine an appropriate antimicrobial regimen. Despite bacteriological
      resolution and cardiac surgery the patient died from complications of infective
      endocarditis.

PMID- 7724426
TI  - Sciatica.

PMID- 7724427
TI  - Guidelines for the clinical use and dispensing of thalidomide.

PMID- 7724428
TI  - Pituitary apoplexy after stimulation tests.

PMID- 7724429
TI  - Changing clinical spectrum of liver abscess.

PMID- 7724430
TI  - Bone density measurement in osteogenesis imperfecta may well be important.

PMID- 7724431
TI  - Ileal leiomyoma--cause of undiagnosed chronic iron deficiency anaemia.

PMID- 7724432
TI  - Gestational macromastia not responding to termination of pregnancy.

PMID- 7724433
TI  - Heterochromatin heteromorphism and variation in apolipoprotein A phenotype--a
      pilot study.

PMID- 7724434
TI  - Post-bulbar chronic duodenal ulcer with major upper gastrointestinal bleeding
      from the cystic artery.

PMID- 7724435
TI  - Iatrogenic gall bladder perforation.

PMID- 7724436
TI  - ACE inhibitors in heart failure. What dose?

PMID- 7724437
TI  - The pathogenesis of chronic pancreatitis.
AB  - To date, there is no consensus on the evolution of chronic pancreatitis.
      Comfort's initial proposal of acute pancreatitis progressing to chronic
      pancreatitis was discarded by protagonists of the 'separate' theory. Sarles thus
      stresses the de novo evolution of chronic pancreatitis-acinar protein
      hypersecretion associated with an imbalance of pancreatic stone promoting and
      inhibiting factors. However, the 'necrosis-fibrosis sequence' hypothesis of
      Kloppel and Mallet resurrects the probability of acute pancreatitis leading to
      chronic pancreatitis. Dimagno offers a unifying concept that the degree of acinar
      injury determines the natural history of pancreatitis. Uninhibited release of
      toxic free radicals could be a common end point for various aetiologies resulting
      in acute or chronic pancreatitis. The pathogenesis of chronic calcifying
      pancreatitis of the tropics is possibly no different from alcoholic chronic
      pancreatitis. Neurocrine and paracrine mechanisms have been offered to explain
      pain out of proportion to radiological and histological pancreatic abnormalities
      in minimal change chronic pancreatitis.

PMID- 7724438
TI  - Immunotherapy in the management of sepsis.
AB  - The pathophysiological effects of severe sepsis, septic shock and related
      syndromes result from tissues damaged by the uncontrolled production of the
      mediators of inflammation. Early deaths are related primarily to the acute
      effects of the systemic inflammatory response. Later deaths are related more
      closely to the consequences of multiple organ dysfunction. Monoclonal antibodies
      and other immunotherapies have been developed against bacterial products,
      cytokines and other mediators involved in this systemic inflammatory response.
      Immunotherapies may improve outcome in the critically ill with sepsis if used
      early and as part of the therapeutic regimen of antimicrobial agents and
      intensive care support.

PMID- 7724439
TI  - Stents in the biliary tree.
AB  - Biliary stenting has become established as a valuable method of palliation in
      malignant biliary strictures. The development of percutaneous and endoscopic
      techniques is described and illustrative cases are shown. The role of
      percutaneous vs endoscopic procedures is examined.

PMID- 7724440
TI  - A model for rational introduction of new and expensive medicines.
AB  - The reported impact of human monoclonal IgM antibody (HA1A) on the mortality rate
      from Gram-negative bacteraemia aroused considerable interest in its use in
      Glasgow Royal Infirmary. However, the commercial preparation of HA1A was
      extremely expensive. With this in mind, the Infirmary's Drugs and Therapeutics
      Committee introduced a system whereby the commercial preparation of HA1A could be
      introduced in a controlled fashion, thereby establishing a model which would
      encourage targeting the prescription of new, highly expensive treatments to
      appropriate patients. This model provides the clinician with a set of objective
      criteria to be met before prescribing such a preparation, thus preventing
      unnecessary increases in the hospital drug budget and justifying using expensive
      resources.

PMID- 7724442
TI  - Dysphagia, a reversible cause not to be forgotten.
AB  - An 84-year-old man presented with dysphagia two years after the onset of
      symptoms. Repeated assessments at both ENT and neurology clinics had not recorded
      any of the more classical signs of Parkinson's disease and these did not become
      apparent until intercurrent illness had been treated. Once diagnosed, treatment
      was started and dramatic improvement was seen.

PMID- 7724441
TI  - Effect of Helicobacter pylori eradication on peptic ulcer healing.
AB  - In a prospective study designed to assess the effect of Helicobacter pylori
      eradication on peptic ulcer healing, 85 consecutive patients with H. pylori
      positive peptic ulcer disease were treated with a triple therapy regimen
      consisting of colloidal bismuth subcitrate 120 mg four times daily for 28 days,
      with metronidazole 400 mg three times daily and tetracycline 500 mg three times
      daily for the first seven days of treatment. H. pylori status was assessed by CLO
      test and histology at least four weeks after completing therapy. Of 75 patients
      (88%) H. pylori-negative after therapy, 69 (92%) had healed ulcers compared with
      only five of 10 patients (50%) who remained H. pylori-positive (p = 0.003).
      Cigarette smoking had no significant effect on ulcer healing. Our results suggest
      that H. pylori eradication may accelerate ulcer healing and provide further
      evidence that an effective helicobactericidal regimen is the treatment of choice
      in H. pylori-positive peptic ulcer.

PMID- 7724443
TI  - Pneumocystis carinii pneumonia presenting with pneumomediastinum in an HIV
      positive patient.
AB  - A 19-year-old man presented with community-acquired pneumonia, complicated by
      pneumomediastinum. Subsequently he was found to be HIV-positive, and to have
      Pneumocystis carinii pneumonia.

PMID- 7724444
TI  - Descending necrotising mediastinitis.
AB  - Descending necrotising mediastinitis is a rare but serious complication of
      oropharyngeal infections with high mortality. Diagnosis is frequently delayed,
      contributing to this high mortality, but awareness of such a complication and
      early diagnosis using computed tomographic scanning leads to prompt surgical
      drainage, proper antibiotic therapy, and survival.

PMID- 7724445
TI  - Genetic variation in body temperature and its response to short-term acute heat
      stress in broilers.
AB  - Genetic variation in body temperature of broilers and its response to short-term
      acute (43.5 C for 45 min) heat stress was studied. Body temperatures before (T0)
      and after (T45) heat exposure were recorded and the changes in body temperature
      (T delta) were calculated for 5-wk-old chicks from 32 broiler sire families. The
      T0 data were utilized to rank the families as to their relative body temperature
      and used to conduct a one-generation divergent family selection program for high
      basal body temperature (H-BT) and low basal body temperature (L-BT). A control
      (C) line was established by random selection from the nonselected birds. There
      was little genetic variation in the base broiler population for body temperature,
      and one generation of selection for divergence in T0 did not result in
      differences. There were also no differences among lines in T45. Low realized
      heritability estimates of .09 and .17 were obtained for T0 in the L-BT and H-BT
      lines. Phenotypic correlations between body temperature and body weight were very
      low for all groups. Highly significant negative correlations were observed
      between T0 and T delta after heat exposure. The T0 fluctuated during the course
      of each day and between days. The adjustment of the data to eliminate this
      variation did not result in increased heritability estimates.

PMID- 7724446
TI  - Inheritance of carcass variables when giant jungle fowl and broilers achieve a
      common physiological body weight.
AB  - Ten chicks each from Giant Jungle Fowl (JF), broiler breeders (BB), and the
      respective F1 cross between them, were reared under typical broiler management
      practices until they reached a market weight of approximately 1,818 g. When
      individual birds reached market weight they were killed by CO2 asphyxiation and
      variables (length and weight) associated with organ, muscle, and skeletal growth
      were measured. Age to market weight demonstrated parental and heterotic effects.
      The JF had more deboned leg muscle and less Pectoralis major muscle than BB.
      Abdominal fat was higher in BB and showed positive heterosis. Organ weights were
      consistently lower for JF than BB. Positive heterosis was observed for spleen and
      pancreas, and negative heterosis was indicated for heart, liver, and lung. The
      digestive tract generally weighed less and was shorter in length for JF than for
      BB. Positive heterosis was observed for proventriculus and gizzard weight, and
      negative heterosis was noted for duodenum and jejunum lengths. Parental line
      differences were observed for most bone variables, including weight and length.
      Parental lines differed for femur breaking strength, but not for tibiotarsus
      breaking strength. A large negative heterotic effect was observed for tibiotarsus
      bone breaking strength.

PMID- 7724447
TI  - Divergent selection for growth in Japanese quail under split and complete
      nutritional environments. 8. Progress from generations 18 through 30 following
      change of selection criterion.
AB  - Following 17 generations of divergent selection for 4-wk BW under split- (SD) and
      complete- (CD) diet environments, two sublines were established from high (H-SD
      and H-CD) BW lines. Subline H-SDG derived from the H-SD line was selected for BW
      gain from 2 to 4 wk under the SD environment, whereas Subline H-CDG derived from
      the H-CD line was similarly selected under the CD environment. These two sublines
      were maintained and reproduced simultaneously with H-SD, L-SD, H-CD, L-CD lines
      from Generation 18 through 30. The purpose of changing the selection criterion
      was to investigate genetic variation in BW gain independent of changes that occur
      immediately following hatch. Selection progress and heritabilities (approximately
      .3) in BW lines (H-SD, H-CD, and L-SD) were similar from Generation 18 through
      30. However, progress and heritability (approximately .1) was not as great in the
      L-CD line. These responses indicate that considerable additive genetic variation
      for 4-wk BW remains in these lines. Selection for increased BW gain from 2 to 4
      wk in both sublines (H-SDG and H-CDG) resulted in smaller BW at 2 wk of age than
      did selection for 4-wk BW. Under the SD environment, H-SDG quail were smaller at
      4 wk than H-SD quail following 12 generations of selection, whereas under the CD
      environment, H-CDG quail were larger than H-CD quail. Results indicate that
      selection for BW gain was more effective under the CD than SD environment and
      that the lack of improvement in 2-wk BW accompanying the increase in BW gain may
      adversely influence the potential benefits obtainable from selection for gain.

PMID- 7724448
TI  - Daily energy allotments and performance of broiler breeders. 1. Males.
AB  - The effects of daily energy intake on reproductive performance of Arbor Acres
      males and on growth of their offspring was studied. In Experiment 1, 21 males
      were placed in individual pens with 12 females. Three rations, differing in
      energy, were fed from 24 to 57 wk of age with seven males receiving either 300,
      340, or 380 kcal ME/d. In Experiment 2, 32 individually caged males were given
      daily allotments of 280, 320, 360, or 360 kcal ME/d from 26 to 32 wk of age and
      300, 340, 380, or 380 kcal ME/d from 32 to 38 wk. Rations of the two groups of
      males fed the highest energy level differed in formulation, one being the same
      wheat short-based basal ration as fed to the two lower energy groups, only with
      additional fat, and the other being a corn-soybean-based ration. Body weight and
      testes weight were increased with increased energy allotment in both experiments
      but carcass composition was unaltered. There were no significant effects of
      energy intake on fertility or hatchability in either experiment. Even though mean
      differences were not significant, fertility in two pens dropped to near zero at
      38 wk in Experiment 1. Semen characteristics and plasma testosterone
      concentrations were unaffected by energy intake in Experiment 2. There was a
      significant linear increase in 6-wk BW of broilers associated with the increase
      in sire energy intake in each of three batches of broilers grown in Experiment 1
      and in one of two batches of broilers grown in Experiment 2.

PMID- 7724449
TI  - Daily energy allotments and performance of broiler breeders. 2. Females.
AB  - Arbor Acres broiler breeder hens, 21 to 61 wk of age, were given the daily ME
      level recommended by the primary breeder for their age and level of production
      (100% AA) or were given 94 or 88% of that amount. The reduction in daily energy
      allotment had no effect on age at 50% or age at peak production, but there was a
      highly significant linear decrease in the eggs per hen from 165 +/- 2.8 in hens
      given 100% AA to 149 +/- 3.2 and 141 +/- 3.8 in hens given 94 and 88% AA. The
      percentage of nonlaying hens between 44 and 60 wk of age was substantially
      increased as daily energy allotment was reduced. The percentage settable eggs was
      significantly lower in the 100% AA group, but no differences in fertility or
      hatchability were seen. Chicks per hen fell from 123 +/- 2.4 to 116 +/- 2.4 to
      102 +/- 2.6 as energy allotment was progressively reduced. Dietary energy
      allotment had no effect on egg weight, shell weight, shell characteristics, or
      proportion of albumen and yolk. Chick weight was unaffected but chicks' liver
      weight increased with increasing dam energy intake. Percentage lipid in hens'
      carcasses increased with increasing energy intake and percentage protein and
      percentage ash decreased.

PMID- 7724450
TI  - Evaluation of a noninvasive technique for measuring fat-free mass in poultry.
AB  - Total body electrical conductivity (TOBEC) has been successfully used to predict
      fat-free mass and lipid content in various species of mammals and birds. In the
      current trial, TOBEC was used to predict fat-free mass in broiler chicks through
      14d posthatch. To accomplish this, a calibration equation was developed and then
      tested for accuracy of prediction. It was determined that two calibration
      equations (hatch to 4 d and 6 to 14 d) were necessary to predict growth.
      Equations including only the TOBEC reading had R2 values of .92 (6 to 14 d) and
      .96 (hatch to 4 d). Equations including additional measures of length or weight
      had slightly improved R2 values. Through the verification of the calibration
      equations it was found that when the equations were used in the appropriate
      range, 95% of the variation in fat-free mass was explained. It was determined
      that TOBEC measures can be used to predict fat-free mass in live broiler chicks
      to 2 wk posthatch.

PMID- 7724451
TI  - Effects of environment on growth, efficiency of feed utilization, carcass
      fatness, and their association.
AB  - The effects of environmental factors (house type, temperature, and type of
      watering system) on gain (G), feed consumption (FC), feed conversion (FCR),
      accumulation of abdominal fat (AF), and the association between FCR and AF of
      broilers were studied in a series of seven experiments. In addition, the
      adjustment of broilers to new housing environments and the factors affecting this
      adjustment were evaluated. The 4- to 7-wk G and FC were greater in groups raised
      at 21.1 C than 26.7 C. There were no consistent effects of environmental
      temperature on FCR (significantly reduced in 21.1 C groups compared with the 26.7
      C groups in two of four trials) or in AF (significantly greater in 21.1 C groups
      than in 26.7 C groups in one of four trials). Environmental temperatures had no
      consistent effect on the relationship between FCR and AF. Both waterer types and
      environmental temperature affected the adjustment of broilers to placement in
      individual cages. Adjustment was better (less mortality and shorter periods of
      reduced FC) in the 21.1 C environment and when cup instead of trough waterers
      were provided. The 4- to 6-wk G and FC were reduced in the caged birds compared
      with the floor pen birds, but the FCR and AF were not consistently different. The
      initial (4-wk) BW significantly affected the 6-wk BW, G, FC, and FCR, but was not
      correlated with AF.

PMID- 7724452
TI  - Effects of feeding Fusarium fujikuroi culture material, containing known levels
      of moniliformin, in young broiler chicks.
AB  - An experiment was conducted with 270 male broiler chicks to evaluate the effects
      of a Fusarium fujikuroi M-1214 culture material containing moniliformin (M) on
      broiler chicks. Day-old chicks were allotted randomly to dietary treatments
      containing 0, .24, .48, .72, .96, 1.44, 1.92, 2.40, and 2.88% M culture material
      (MCM). These levels of MCM supplied 0, 25, 50, 75, 100, 150, 200, 250, or 300 mg
      M/kg of feed. Each dietary treatment was fed to six pen replicates of five chicks
      per pen for 21 d. Significant mortality (P < .05) occurred in chicks fed 200 (8
      out of 30), 250 (17 out of 30), and 300 (25 out of 30) mg M/kg feed. Chicks fed >
      100 mg M/kg had lower (P < .05) feed intakes and smaller BW gains (P < .05) than
      controls. Increased heart weights (P < .05) were observed in chicks fed > 50 mg
      M/kg, and increased liver weights (P < .05) in chicks fed > 100 mg M/kg. Gross
      lesions of M toxicity included generalized cardiomegaly with dilation of the
      right ventricle. Histopathology revealed a high incidence of large and variably
      shaped cardiomyocyte nuclei and a generalized loss of cardiomyocyte cross
      striations in chicks fed > 75 and 200 mg M/kg, respectively. Results indicated
      that F. fujikuroi culture material containing M is toxic to young broiler chicks.

PMID- 7724453
TI  - Influence of fumonisin B1, present in Fusarium moniliforme culture material, and
      T-2 toxin on turkey poults.
AB  - Diets containing 300 mg fumonisin B1 (FB1)/kg of feed and 5 mg T-2 toxin/kg of
      feed singly or in combination were fed to female turkey poults (Nicholas Large
      White) from day of hatch to 21 d of age. When compared with controls, 21-d body
      weight gains were reduced 21% by FB1, 26% by T-2, and 47% by the combination. the
      efficiency of feed utilization was adversely affected by FB1 and the combination
      of FB1 and T-2. Relative weights (grams/100 g BW) of the liver and gizzard were
      increased in poults fed the FB1 and the combination diets; whereas, the relative
      weight of the pancreas was increased in all treated groups. All poults were
      scored for oral lesions using a scale of 1 to 4 (1 = no visible lesions, 4 =
      severe lesions). Oral lesions were present in all poults fed the T-2 diet
      (average score of 3.29) or the combination diet (average score of 3.54). Serum
      concentration of cholesterol was decreased and lactate dehydrogenase activity was
      increased in poults fed the FB1 and combination diets. The activity of aspartate
      aminotransferase and the values for red blood cells, hemoglobin, and hematocrit
      were increased only in poults fed the combination diet. Inorganic phosphorus
      concentration was decreased only in poults fed the combination diet. The
      increased toxicity in poults fed the combination diet for most variables can best
      be described as additive, although some variables not altered by FB1 or T-2
      singly were significantly affected by the combination, indicating that the
      combination may pose a potentially greater problem to the turkey industry than
      either of the mycotoxins individually.

PMID- 7724454
TI  - Furosemide reduces the incidence of pulmonary hypertension syndrome (ascites) in
      broilers exposed to cool environmental temperatures.
AB  - The incidence of pulmonary hypertension syndrome (PHS; ascites) was evaluated in
      two experiments using broiler breeder male by-product chicks exposed after 3 wk
      of age to cool environmental temperatures (10 to 15 C). In Experiment 1, 3- to 6
      wk-old birds were fed a grower diet to which 0 (Control), .001, .005, .010, or
      .015% furosemide had been added. All groups in Experiment 1 were fed a finisher
      ration containing no furosemide during Weeks 7 to 8. In Experiment 2, the Control
      group received no furosemide, a second group received .015% furosemide during the
      grower phase only (Weeks 3 to 6), and the third group received .015% furosemide
      during the grower and finisher phases (Weeks 3 to 8). Cumulative PHS mortality
      was significantly reduced by furosemide in both experiments. Compared with
      Controls, birds fed .015% furosemide did not have lower (P = .077) final body
      weights in Experiment 1 but did have significantly lower final body weights in
      Experiment 2. Lower levels of furosemide significantly reduced PHS mortality
      without reducing body weights. Furosemide did not improve feed conversion in
      either experiment. Neither body weight on Day 1 or 21 nor net Day 1 to 21 weight
      gain were predictive of susceptibility to PHS during the subsequent grower and
      finisher intervals in either experiment. On Day 55 of Experiment 2, large healthy
      birds fed .015% furosemide had significantly lower right:total ventricular weight
      ratios than control birds, indicating that furosemide reduced right ventricular
      hypertrophy, presumably by reducing pulmonary arterial pressure.

PMID- 7724455
TI  - Supplemental L-arginine attenuates pulmonary hypertension syndrome (ascites) in
      broilers.
AB  - The incidence of pulmonary hypertension syndrome (PHS; ascites) was evaluated in
      two experiments using broiler breeder male by-product chicks exposed after 3 wk
      of age to cool environmental temperatures (10 to 15 C). In Experiment 1, 3- to 6
      wk-old birds were fed a grower diet to which 0 (Control), .25, .5, or 1%
      supplemental L-arginine HCl had been added. During Weeks 7 to 8, all groups in
      Experiment 1 were fed a finisher diet containing no supplemental arginine. In
      Experiment 2, the Control group received no supplemental arginine, a second group
      was fed a grower diet supplemented with 1% L-arginine HCl (Weeks 3 to 6), and a
      third group was fed grower and finisher diets supplemented with 1% L-arginine HCl
      (Weeks 3 to 8). Cumulative PHS mortality was significantly reduced by 1% L
      arginine HCl on Days 34 to 46 in Experiment 1. When data from all birds fed
      grower or finisher diets supplemented with 1% L-arginine HCl were pooled in
      Experiment 2, cumulative PHS mortality was marginally lower (P = .065) than for
      the Control group. Supplemental L-arginine HCl had no effect on final body
      weights, weight gain, or feed conversion in either experiment. Neither body
      weight on Day 1 or 21 nor net weight gain from Days 1 to 21 determined
      susceptibility to PHS during the subsequent grower and finisher intervals in
      either experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724456
TI  - Feeding behavior and growth of broiler chicks fed larvae of the darkling beetle,
      Alphitobius diaperinus.
AB  - Experiments were conducted to determine the effects of feeding larvae of the
      darkling beetle (lesser mealworm), Alphitobius diaperinus (Panzer) (Coleoptera:
      Tenebrionidae) to broiler chicks on chick growth. Chicks readily fed on the
      larvae and exhibited reduced growth in the absence of other feed. Chicks 3 to 8 d
      old restricted to a diet of only larvae consumed 1,552 +/- 172 (mean +/- SD)
      larvae per chick per day and their body weights were significantly less (mean =
      84 g) at the end of the 6 d than for chicks on starter feed during the same time.
      After return to starter feed for 8 d after feeding on larvae for 6 d, the chicks
      did not compensate for the reduced weight and their body weights were
      significantly less (mean = 170 g) than for chicks on starter feed for the 14 d.
      Chicks from age 2 through 9 d were given a choice between broiler starter feed
      and darkling beetle larvae. The numbers (mean +/- SD) of larvae consumed per
      chick per day were: 389 +/- 18, 631 +/- 14, 496 +/- 20, and 287 +/- 33, for Days
      2 to 3, 4 to 5, 6 to 7, and 8 to 9, respectively. The body weight of chicks
      feeding on starter feed and larvae was significantly greater than the weight of
      chicks consuming feed only. In the presence of larvae, the mean feed consumption
      per chick was less than for chicks provided with only starter feed. The beetle
      larvae were 68% crude protein and 21% fat (DM basis) and had higher amounts of 18
      amino acids than the starter feed.

PMID- 7724457
TI  - Validation of an assay to measure adrenocorticotropin in plasma and from chicken
      leukocytes.
AB  - A RIA for mammalian adrenocorticotropic hormone (ACTH) was modified and validated
      to measure chicken ACTH. The assay was capable of detecting an increase in
      chicken plasma ACTH following treatments known to increase plasma ACTH. Both
      splenic and peripheral blood leukocytes stimulated with corticotropin-releasing
      factor (CRF) showed a significant increase in ACTH production compared with
      unstimulated leukocytes. This finding supports the conclusion that the substance
      produced by leukocytes previously shown in our laboratory to stimulate adrenal
      cells to secrete corticosterone is immunoreactive ACTH.

PMID- 7724458
TI  - A modified bioassay for energy utilization in newly hatched chicks. 2.
      Determination of feed input and procedures to estimate endogenous energy loss.
AB  - Two experiments were conducted to develop a modified bioassay system to determine
      bioavailability of dietary energy in newly hatched chicks based on the TME assay
      system. Broiler chicks aged 0, 1, 3, 7, and 14 d old were force-fed or consumed
      feed ad libitum following 24 h of feed withdrawal to determine the optimum level
      for feed input. In the second experiment, 7-d-old chicks were force-fed various
      diets and feedstuffs at three levels following 24 h of feed deprivation. Linear
      regressions (P < .01) between energy input (X) and excreted energy (Y) were
      demonstrated irrespective of diets and feedstuffs at any age in Experiments 1 and
      2. Endogenous energy loss (EEL), estimated by the regression method and
      approximated over a small range was lower than EEL estimated using feed-deprived
      chicks. The TME and TMEn values of diets and feedstuffs calculated using EEL
      estimated by the regression method were not modulated by the feed input level,
      whereas those estimated by feed-deprived chicks tended to increase with decreases
      in the level of feed input. Thus, a modified method for determination of energy
      utilization in newly hatched chicks based on TME assay is proposed, which seems
      to have proper physiological and chemical bases.

PMID- 7724459
TI  - Absorption of silicon and aluminum by hens fed sodium zeolite A with various
      levels of dietary cholecalciferol.
AB  - Two experiments were conducted to determine whether 1) serum Si and Al is
      increased in hens intubated with sodium zeolite A (SZA); and 2) dietary
      cholecalciferol (vitamin D3) influences the absorption of Si or Al by hens fed
      SZA. In Experiment 1, hens were intubated at oviposition with 0, 1, or 2 g of
      SZA. Blood samples were collected from the brachial vein at oviposition, and 4,
      8, 12, 16, and 20 h postoviposition. Serum samples were analyzed for Si and Al.
      Peak serum Si and Al were observed at 4 and 8 h postoviposition, respectively. In
      Experiment 2, hens consumed commercial layer diets ad libitum containing five
      levels of dietary cholecalciferol (100 to 500 IU/kg) with or without .75% SZA for
      6 wk. Blood samples were collected at the end of the 6-wk period by cardiac
      puncture at oviposition. When dietary cholecalciferol was increased from 100 to
      200 IU/kg of diet there was an increase (P < .05) in serum Si but not Al. Levels
      of cholecalciferol above 200 IU/kg did not produce an additional increase in
      serum Si. The results showed increased (P < .01) serum concentrations of Si and
      Al for hens intubated with or fed SZA. It was concluded that Si and Al from SZA
      are absorbed by commercial Leghorn hens, and a possible involvement of Si or Al
      should be considered in the mechanism of action of SZA associated with improved
      eggshell quality and bone development.

PMID- 7724460
TI  - Dietary copper in excess of nutritional requirement reduces plasma and breast
      muscle cholesterol of chickens.
AB  - Male commercial broiler strain chickens were fed from hatching to 42 d of age
      either a control diet (based on corn and soybean meal) or the control diet
      supplemented with 250 mg copper/kg diet from cupric sulfate pentahydrate (for 35
      or 42 d). Hypocholesterolemia (11.8% reduction) and decreased breast muscle
      cholesterol (20.4% reduction) were observed in copper-supplemented birds. There
      was a slight increase (P > .05) in breast muscle copper (14.5%), and all levels
      were very low (< .5 mg/kg). Feeding copper for 42 vs 35 d resulted in lower
      levels of cholesterol in the plasma (12.9 vs 10.8% reduction) and breast muscle
      (24.6 vs 16.2% reduction). Very similar results were found in two additional
      experiments in which hypocholesterolemia and reduced breast muscle cholesterol
      were associated with reduced plasma triglycerides and blood reduced glutathione.
      It is well known that hypercholesterolemia is a symptom of dietary copper
      deficiency. The data presented here indicate that blood and breast muscle
      cholesterol are inversely related to dietary copper in excess of the dietary
      requirement for maximal growth. The cholesterol content of the edible muscle
      tissue of broiler chickens can be reduced by approximately 25% after feeding a
      supranormal level of copper for 42 d without altering the growth of the chickens
      or substantially increasing the copper content of the edible meat.

PMID- 7724461
TI  - Digestion and absorption in the young chick.
AB  - Digestion, enzyme secretion and intestinal rate of passage were determined in
      broiler chicks from hatch until 21 d using 141Ce as a nonabsorbed reference
      substance. Body weight and feed intake increased more rapidly after 10 d
      posthatch, and, in parallel, time of passage of feed through the intestines
      decreased by approximately 33%. Net duodenal secretion of amylase, trypsin, and
      lipase was low at 4 d and increased 100-, 50-, and 20-fold, respectively, by 21
      d. Enzyme activity decreased distally in the small intestine. This change was
      greater with age. The contribution of the ileum to fatty acid absorption
      decreased after 7 d. Small intestine digestion of nitrogen increased from 78% at
      4 d to 92% at 21 d, whereas fatty acid and starch digestion ranged from 82 to 89%
      in this period. It appears that digestibilities of starch and lipids are not
      limiting factors in the growth of young chicks.

PMID- 7724462
TI  - The concentration of different lipid classes during late embryonic development in
      a randombred turkey population and a subline selected for increased body weight
      at sixteen weeks of age.
AB  - Lipid changes in the yolk sac of the embryo were studied in a randombred
      population of turkeys (RBC2) and a subline of the RBC2 selected for increased BW
      at 16 wk (F line). Comparisons of yolk sac and embryonic development were made
      between 22 d of incubation and hatch (28 d). Poults from the F line had heavier
      yolk sacs from 24 to 28 d and yolk free body weight was also heavier at hatch
      (61.1 vs 52.8 g). Yolk sac lipid (percentage of DM) declined faster in F line
      embryos (69 to 39%) compared with the RBC2 line (62 to 48%). In both lines,
      embryonic liver dry matter and lipids (percentage of DM) were similar. Yolk sac
      neutral lipids increased from 22 to 28 d (70 to 80% total lipid) in both lines
      and there was a concomitant decline in phospholipids (30 to 20%). The direction
      of the changes was similar for embryonic liver lipid. At 26 and 28 d, there were
      significantly increased neutral lipids (94 vs 88%) and decreased phospholipids (6
      vs 12%) in RBC2 compared with F line embryonic livers. The concentration of
      cholesterol esters (percentage of total lipid) increased in the yolk sac and
      embryonic liver during the course of incubation. At 26 and 28 d, livers from RBC2
      embryos had increased cholesterol ester concentration compared with livers from
      the F line.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724463
TI  - The effects of halofuginone and salinomycin, alone and in combination, on live
      performance and skin characteristics of female broilers: influence of a high
      proline diet supplemented with ascorbic acid and zinc.
AB  - Live performance and carcass quality of female broilers were evaluated under four
      coccidiostat programs (CP) and two feed treatments. The CP consisted of
      halofuginone (H) and salinomycin (S), fed either continuously (HH and SS) or in
      rotational programs (HS and SH), during the starter (1 to 21 d) and grower (22 to
      35 d) periods, respectively. All groups received an unmedicated withdrawal feed
      from 36 to 42 d. Feed treatments consisted of a control and a fortified diet high
      in proline and supplemented with additional ascorbic acid and zinc (50 birds per
      pen; 4 pens per feed; 8 pens per CP). In addition to live performance and skin
      puncture strength, carcass quality attributes following processing (at 43 d of
      age) were assessed. No CP by feed interactions were detected for any of the
      variables measured. The CP treatments did not differ for live performance. Birds
      on fortified feed were heavier at 21 d (P < .001) and had an improved feed
      conversion at 42 d (P < .05). Skin puncture strength was significantly reduced
      for the birds fed H, either in continuous (HH) or rotational programs (HS and
      SH). Skin sores-scratches and tears were lowest for the SS and SH groups. The HH
      treatment resulted in fewer grade A carcasses (P < .001). Halofuginone, when fed
      continuously or in the starter feed, affected carcass quality of broilers. Higher
      dietary proline or supplementation with ascorbic acid and zinc did not appear to
      alleviate the effects of halofuginone on skin quality.

PMID- 7724464
TI  - The effects of halofuginone and salinomycin, alone and in combination, on live
      performance and skin characteristics of broilers.
AB  - Live performance and skin characteristics of male and female broilers were
      evaluated under four coccidiostat feed additive programs. Treatments consisted of
      halofuginone (H) and salinomycin (S), fed either continuously (HH and SS) or in
      rotational programs (HS and SH) during the starter (1 to 21 d) and grower (22 to
      35 d) periods, respectively. An unmedicated withdrawal feed was provided from 36
      to 42 d of age. Body weights, feed efficiency, and mortality (by pen) were
      determined, in addition to skin puncture strength measurements taken at Days 21,
      35, and 42 on five birds per pen. At 43 d of age, all birds were processed and
      individually graded for skin defects. There were no treatment by sex interactions
      for any variable measured. Male body weights, feed efficiency, and total
      mortality exceeded those of females (P < .05). Skin puncture strength was reduced
      at 21 d in the HH and HS groups, at 35 d in the HH and SH groups, and at 42 d in
      the HH, HS, and SH groups. Thigh sores and scratches were higher for the HH group
      (P < .05), and thigh skin tears were higher for the HH and HS groups (P < .01).
      Males had more swollen hock joints and breast blisters than females (P < .001).
      Females had more thigh skin tears (P < .01) and broken wings (P < .001) than
      males. Results of the present study demonstrated that halofuginone affected skin
      strength of broilers, especially when used continuously or only in the starter
      feed (1 to 21 d).

PMID- 7724465
TI  - Effects of feed restriction on growth and reproduction in randombred and selected
      lines of Japanese quail.
AB  - Feed restriction (70% of ad libitum consumption) was carried out from 1 d after
      hatching until 44 d in a randombred quail line and until 28 d in a quail line
      selected for high 4-wk BW. Body weights of restricted quail were significantly
      lower than ad libitum controls during restriction. Two weeks after restriction
      ended, however, BW were no longer different. Mortalities were twice as high under
      restriction. Hatchability of eggs was not affected by restriction, but restricted
      quail of the selected line laid fewer double-yolk eggs than ad libitum controls.

PMID- 7724466
TI  - Determination of carotenoid pigments, retinol, and alpha-tocopherol in feeds,
      tissues, and blood serum by normal phase high performance liquid chromatography.
AB  - A normal phase HPLC method employing a hexane:ethyl acetate mobile phase solvent
      gradient for the simultaneous separation and quantification of carotenoid
      pigments and vitamins A and E has been developed. The gradient consists of a 10
      min linear change from 1 to 2 mL/min and 95:5 to 70:30 hexane:ethyl acetate
      mobile phase, which is followed by 7 min of isocratic mobile phase of 70:30
      hexane:ethyl acetate at 2 mL/min. The stationary phase consisted of a 4-mu silica
      column. A photodiode array detector generated simultaneous chromatogram data at
      three wavelengths (294, 325, and 445 nm) with broad spectrum data at peaks. The
      method produced good separation of trans-lutein and zeaxanthin.

PMID- 7724467
TI  - Iron requirement of chicks fed a semipurified diet based on casein and soy
      protein concentrate.
AB  - An Fe depletion and repletion study was conducted to determine the Fe requirement
      of chicks fed a casein-dextrose diet containing soy protein concentrate. Weight
      gain, hematocrit, hemoglobin, and serum total Fe showed marked increases when
      graded levels (0, 5, 10, 20, 30, 40, and 50 mg/kg) of Fe from analytical grade
      FeSO4.7H2O were added to an Fe-deficient basal diet containing 46.5 mg Fe/kg.
      Subjecting the hemoglobin data to broken-line analysis indicated that the Fe
      requirement was 38.5 mg/kg of supplemental Fe (i.e., total dietary Fe of 85
      mg/kg). Heart hypertrophy was observed in Fe-deficient chicks, but Fe
      supplementation (more than 20 mg/kg) alleviated the problem.

PMID- 7724468
TI  - Evaluation of different metrics as indirect measures of rate of drug absorption
      from extended release dosage forms at steady-state.
AB  - Bioequivalence assessment of extended release (ER) dosage forms is usually
      carried out at steady-state, using area under the curve (AUC) to evaluate extent
      of absorption and maximum concentration (Cmax) and % peak trough fluctuation
      ratio (%PTF) to evaluate rate of absorption. Other metrics such as Cmax/AUC and
      partial AUCs have recently been proposed as alternatives for assessing the
      absorption rate of drugs from immediate release (IR) dosage forms under single
      dose conditions. The performances of these metrics were assessed using the
      results of two sets of simulated experiments of ER dosage forms at steady-state
      and 2 actual pharmacokinetic studies involving ER dosage forms of a Glaxo drug.
      In the first set of simulations there was no difference in bioavailability
      between the two formulations; in the second set of simulations the test
      formulation had a 50% greater absorption rate-constant (ka) than the reference
      formulation. The following conclusions were reached: 1. For ER dosage forms at
      steady-state, all the metrics, with the exception of %PTF, resulted in much
      smaller increases than the underlying 50% increase in ka. Although, %PTF gave the
      largest effect it was also the most imprecisely estimated. 2. In our studies,
      none of the metrics tested provided reliable information about changes in the
      underlying rate of absorption from ER dosage forms under steady-state conditions.
      3. The current practice of comparing rate of absorption from ER dosage forms
      using steady-state Cmax is inappropriate due to lack of sensitivity. The use of
      %PTF may require a widening in the currently accepted 80-125% permissible range
      set for Cmax and AUC.

PMID- 7724469
TI  - Penetration kinetics of 2',3'-dideoxyinosine in dermis is described by the
      distributed model.
AB  - The present study evaluated the kinetics of drug penetration in the dermis. A rat
      was given a dermal dose of 2',3'-dideoxyinosine (ddI). At 6 hr, the skin tissue
      was excised, immediately frozen and sectioned, and the decline of drug
      concentration as a function of tissue depth was determined. The tissue
      concentration-depth profile showed a semilogarithmic decline, as would be
      expected in a distributed tissue kinetic model which incorporates diffusion and
      capillary membrane transport. The goodness of fit of the profiles by the simple
      diffusion and the distributed models were compared using four statistical
      criteria, i.e., coefficient of determination. Akaike Information criterion,
      Schwartz criterion and Imbimbo criterion. These analyses showed that the decline
      of tissue concentration versus tissue depth in the dermis was better described by
      the distributed model than by the diffusion model in all 7 animals. To examine
      the effect of blood perfusion on the tissue concentration-depth profiles, some of
      the tissues were frozen after 1 and 2 hr storage at room temperature. In contrast
      to the adjacent tissues frozen immediately, the concentration-depth profiles in
      tissues frozen after a 1-2 hr delay were described equally well by distributed
      and diffusion models. A comparison of the concentration-depth profiles in the
      tissues processed immediately or after a delay showed a 7 fold more shallow slope
      and a 60% lower concentration at the epidermis-dermis interface after storage.
      However, storage did not alter the total amount of drug in the entire dermis.
      Drug degradation during storage was further ruled out by the insignificant ddI
      degradation in 10% skin homogenate (a half-life of approximately 70 hr).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7724470
TI  - Pharmacokinetics of antimony in patients treated with sodium stibogluconate for
      cutaneous leishmaniasis.
AB  - The pharmacokinetics of Sb was examined in 29 patients with cutaneous
      leishmaniasis following the intramuscular administration of a dose of sodium
      stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time
      intervals from each patient and Sb was measured in whole blood by electrothermal
      atomic absorption spectrophotometry after an appropriate dilution with Triton X
      100. The 24-hr urine was also collected and analyzed similarly. The blood
      concentration-time data conformed to the one-compartment open model with mean and
      (SEM) of the apparent first-order rate constants for absorption (ka) and
      elimination (kd) of 1.71 (0.15) and 0.391 (0.016) hr-1, respectively. The maximum
      concentration of Sb achieved was 8.77 (0.39) mg/L and the peak time was 1.34
      (0.09) hr. The total body clearance (TBC) and the volume of distribution (Vd)
      were 17.67 (1.38) L/hr and 45.7 (2.6) L, respectively, assuming a complete
      absorption. The fraction of dose of Sb excreted in the urine was 0.80 (0.07) and
      the renal clearance was 12.7 (1.16) L/hr. The frequency distribution pattern of
      the area-under-the-curve (AUC) appears to be bimodal and separates patients into
      those with low exposure to Sb (AUC = 11.7-29.04 mg.hr/L) (i.e., rapid
      eliminators) and those with high exposure to Sb (AUC = 31.5-49.1 mg.hr/L) (i.e.,
      slow eliminators). This may explain the variability observed in the response to
      treatment of leishmaniasis with sodium stibogluconate.

PMID- 7724471
TI  - Assessment of toxicokinetics and toxicodynamics following intravenous
      administration of etoposide phosphate in beagle dogs.
AB  - The toxicokinetics and toxicodynamics of etoposide phosphate (BMY-40481), a water
      soluble phosphate ester derivative of etoposide, were investigated in beagle dogs
      (N = 4) following 5 min i.v. infusion doses equivalent to 57, 114 and 461 mg/m2
      of etoposide. The doses were administered in sequence starting with the low dose.
      There was a 28 day wash-out period between the doses. Serial blood samples were
      collected over 32 hr and the levels of intact BMY-40481 and etoposide in plasma
      were measured using validated HPLC assays. Hematology profiles were obtained at
      pre-dose, and twice a week post-dose for 28 days to correlate systemic exposure
      to etoposide and hematologic toxicity. Following i.v. administration, plasma
      concentrations of BMY-40481 declined rapidly. For the 3 doses, mean t 1/2 of BMY
      40481 ranged from 0.11-0.17 hr (6.6-11 min). The mean Cmax and AUC values of BMY
      40481 ranged from 1.72-40.5 micrograms/ml and 0.16-4.14 hr.micrograms/ml,
      respectively. Both systemic clearance and steady state volume of distribution of
      BMY-40481 decreased significantly at the high dose. In contrast, the mean Cmax
      and AUC values of etoposide ranged from 5.46-39.4 micrograms/ml and 2.28-22.6
      hr.micrograms/ml, respectively. Cmax occurred at the end of infusion (5 min) at
      all dose levels, indicating that etoposide was rapidly formed from BMY-40481. The
      apparent systemic clearance (range: 342-435 ml/min/m2) and apparent steady state
      volume of distribution (range: 21.5-26.6 l/m2) of etoposide were dose
      independent. The AUC of etoposide was significantly correlated with hematologic
      toxicity, i.e., percent decreases in white blood count (WBC), absolute neutrophil
      count (ANC) and platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724472
TI  - Hepatic uptake of octreotide, a long-acting somatostatin analogue, via a bile
      acid transport system.
AB  - The hepatic transport mechanism of octreotide (Sandostatin), a somatostatin
      analogue, was studied using freshly prepared rat hepatocytes. The initial uptake
      rate of octreotide represented exclusively a saturable transport process. The
      half-saturation constant, Kt, and the maximum uptake-rate, Jmax, for the uptake
      of octreotide were 91.1 +/- 28.4 microM and 104.6 +/- 19.7 pmol/mg protein/min,
      respectively. An energy requirement was demonstrated for [14C]octreotide uptake
      since metabolic inhibitors (DNP, rotenone, antimycin and NaCN) significantly
      reduced the initial uptake rate. [14C]octreotide uptake was also significantly
      inhibited by ouabain. [14C]octreotide uptake was reduced in the absence of Na+ in
      the uptake medium. [14C]octreotide uptake was significantly inhibited by bile
      acids, iodipamide, d-tubocurarine, whereas it was not inhibited by bilirubin,
      TEMA and insulin. Competitive inhibition of taurocholic acid was observed for
      octreotide uptake with the inhibition constant, Ki, of 82 +/- 17 microM.
      Moreover, a significant inhibitory effect of octreotide was observed for the Na+
      dependent uptake of [14C]taurocholic acid. These results suggest that octreotide
      is transported into hepatocytes via a bile acid carrier-mediated system.

PMID- 7724473
TI  - Applying Bailer's method for AUC confidence intervals to sparse sampling.
AB  - Bailer developed a method for constructing confidence intervals for areas under
      the concentration-vs-time curve (AUC's) with only one sample per subject but with
      multiple subjects sampled at each of several time points post dose. We have
      modified this method to account for estimation of the variances. How the need to
      estimate variances affects study design is discussed. An extension of Bailer's
      method is proposed where variances are modeled as a function of the means, in
      order to get more precise estimates of variances. The modified and extended
      methods are applied to a rat toxicokinetic study with only two rats per time
      point per treatment group.

PMID- 7724474
TI  - The use of intracerebral microdialysis to determine changes in blood-brain
      barrier transport characteristics.
AB  - The aim of this study was to determine whether changes in the transport of drugs
      into the brain could be determined by in vivo intracerebral microdialysis.
      Atenolol was used as a model drug to determine blood-brain barrier (BBB)
      transport characteristics. In rats, unilateral opening of the blood-brain barrier
      was achieved by infusion of hyperosmolar mannitol (25%, w/v) into the left
      internal carotid artery. BBB transport, expressed as the ratio of the area under
      the curve (AUC) of atenolol in brain extracellular fluid over plasma, was three
      times higher for the mannitol treated hemisphere as compared with the
      contralateral brain or after infusion of saline, being (mean +/- SEM) 0.094 +/-
      0.024 (n = 16), 0.029 +/- 0.007 (n = 12) and 0.030 +/- 0.009 (n = 12)
      respectively. Further evaluation of the data indicated that for experiments
      performed in the morning the mannitol infusion had little effect on the extent of
      transport of atenolol into the brain, while in the afternoon BBB transport was
      about 10-fold higher than in the contralateral and saline group. The mean
      "afternoon" ratios +/- SEM were 0.155 +/- 0.038 (n = 8), 0.012 +/- 0.003 (n = 6)
      and 0.018 +/- 0.006 (n = 6) respectively. It is concluded that intracerebral
      microdialysis is capable of revealing changes in BBB transport and regional and
      time-dependent differences in drug levels can be demonstrated with the use of
      this technique.

PMID- 7724475
TI  - Assessment of glucocorticoid lung targeting by ex-vivo receptor binding studies
      in rats.
AB  - Triamcinolone acetonide (TA, 22 micrograms) was given to rats by intravenous
      (i.v.) injection or intratracheal (IT) instillation. Free glucocorticoid
      receptors were monitored over time in liver and lung using an ex-vivo receptor
      binding technique. After i.v. administration of a TA solution, the reduction of
      free receptors over time was very similar in lung and liver (AUCLung = 280 +/-
      47% h; AUCLiver = 320 +/- 76% h). Intratracheal instillation of the same solution
      produced time profiles which mirrored those of i.v. injection (AUCLung = 260 +/-
      41% h; AUCLiver = 330 +/- 50% h). The lack of lung targeting was also reflected
      in the failure to show any significant difference in the pulmonary targeting
      factor T (AUCLung/AUCLiver) between i.v. (T = 0.84 +/- 0.18) and IT (T = 0.78 +/-
      0.03) administration. In contrast, a certain degree of lung specificity was
      observed after IT instillation of a glucocorticoid suspension (22 micrograms;
      AUCLung = 160 +/- 135% h; AUCLiver = 65 +/- 91% h, T = 2.3 +/- 0.5) as indicated
      by significant differences in T between i.v. injection and IT instillation (p =
      0.038). The method presented provides a means of simultaneously assessing
      pulmonary and systemic effects after different forms and routes of administration
      and might be of value in further studying multiple aspects of inhalation
      glucocorticoid therapy.

PMID- 7724476
TI  - Sumatriptan absorption from different regions of the human gastrointestinal
      tract.
AB  - Sumatriptan exhibits low oral bioavailability partly due to presystemic
      metabolism, which may vary with regional differences in metabolic activity
      throughout the gastrointestinal tract. This study evaluated sumatriptan
      absorption in humans after administration orally and by oroenteric tube into the
      jejunum and cecum. Because the site of cecal administration varied,
      pharmacokinetic parameters for sumatriptan and its major metabolite were compared
      statistically only after oral and jejunal administration. One-half of the oral
      dose was recovered in the urine as parent (3%) and metabolite (46%). Sumatriptan
      was absorbed throughout the gastrointestinal tract; absorption was similar after
      oral and jejunal administration, and less after cecal administration. The
      metabolite AUC and the AUC ratio (metabolite/parent) were significantly lower
      after jejunal compared to oral administration; the AUC ratio was two-fold lower
      after cecal administration. Results suggest that presystemic metabolism of
      sumatriptan varies throughout the gastrointestinal tract and/or regional
      differences exist in the absorption of metabolite formed within the
      gastrointestinal tract.

PMID- 7724477
TI  - Comparison of simulated and in-vivo plasma levels of cilastatin following
      intravenous in-line drug administration.
AB  - The primary objective of this work was to establish a method to simulate the
      plasma levels of cilastatin, a model drug, following an intravenous in-line
      delivery scheme. In-vivo data in dogs obtained from this work were used to
      demonstrate the validity of the proposed approach. The in-line drug delivery
      system consists of a drug containing device which is placed between a large
      volume parenteral and a patient. Numerous advantages have been identified for
      this automatic in-line reconstitution delivery system. The numerical convolution
      integral algorithm was used in this work to perform plasma profile simulation.
      The results indicated that the simulated cilastatin plasma profile following in
      line delivery closely agreed with the in-vivo data.

PMID- 7724478
TI  - Evaluation of the intestinal absorption of erythromycin in man: absolute
      bioavailability and comparison with enteric coated erythromycin.
AB  - To determine the role of acid hydrolysis on the gastrointestinal absorption of
      erythromycin, six healthy subjects received erythromycin as a 240 mg intravenous
      dose, a 250 mg oral solution administered via endoscope directly into the
      duodenum and bypassing the stomach, and an enteric-coated 250 mg capsule. Blood
      samples were collected for 6 hours and serum erythromycin quantified by a
      microbiological method. The time to achieve maximum serum concentrations for the
      solution was 0.25 +/- 0.08 (mean +/- SD) hours and for the capsule was 2.92 +/-
      0.55 hours. The absolute bioavailability of erythromycin from the capsule was 32
      +/- 7% and for the duodenal solution 43 +/- 14%. The ratio of the areas under the
      serum erythromycin concentration-time curve of capsule to solution was 80 +/- 28%
      (range 38 to 110%). There is substantial loss of erythromycin apart from gastric
      acid hydrolysis, which cannot be accounted for by hepatic first-pass metabolism.
      Attempts to further improve the oral bioavailability of erythromycin beyond 50%
      by manipulation of formulation are likely to be futile.

PMID- 7724480
TI  - Determination of moisture in intact gelatin capsules by near-infrared
      spectrophotometry.

PMID- 7724479
TI  - Determination of aliphatic thiols by fluorometric high-performance liquid
      chromatography after precolumn derivatization with 2-(4-N-maleimidophenyl)-6
      methylbenzothiazole.
AB  - A sensitive, fluorometric high-performance liquid chromatographic method for the
      detection of aliphatic thiols, following pre-column derivatization with 2-(4-N
      maleimidophenyl)-6-methylbenzothiazole, has been developed. The N-maleimide, the
      acid and the methyl ester derivatives of the commercially available 2-(4
      aminophenyl)-6-methylbenzothiazole were synthesized and found to be equally
      effective for the precolumn derivatization procedure. The resulting fluorescentic
      derivatives of aliphatic thiols were separated on a reversed-phase column
      (Ultrasphere-ODS) using 0.1% hexane-sulfonic acid in 10 mM potassium hydrogen
      phosphate: acetonitrile (65:35) as a mobile phase and were detected
      fluorometrically (excitation 320 nm; emission 405 nm). The method is highly
      sensitive (femtomole range) and is easily applied for determination of SH
      containing drugs and endogenous thiols in biological samples.

PMID- 7724481
TI  - Metabolism of acetylneurotensin(8-13) by proteolytic activities of intestinal
      enterocytes.

PMID- 7724482
TI  - The influence of the shape of the plasma drug concentration profile upon the
      pharmacological effect.

PMID- 7724483
TI  - Vitamin K prodrugs: 1. Synthesis of amino acid esters of menahydroquinone-4 and
      enzymatic reconversion to an active form.
AB  - The efficacy and toxicity of vitamin K depends on the pathway and the extent of
      enzymatic reductive activation to vitamin K hydroquinone, which is an essential
      cofactor for the synthesis of clotting factors. Parenteral use of vitamin K is
      impaired by its water insolubility. With the aim to improve delivery problems
      associated with menahydroquinone-4 (MKH, 2), an active form of menaquinone-4, N,N
      dimethylglycine esters of 2 (1-mono, 4-mono, and 1,4-bis) were synthesized and
      assessed as potential water-soluble prodrugs for parenteral use. The esters can
      deliver the hydroquinone to its active site without a quinone reductive
      activation step. The hydrochloride salts of the esters were found to be quite
      soluble in water. The hydrolysis of the esters in 20% rat liver homogenate 9000 x
      g supernatant, rat plasma and phosphate buffer, pH 7.4, at 37 degrees C was
      kinetically studied in the presence and absence of an esterase inhibitor. The
      hydrolysis was catalyzed by esterases located in the rat liver and rat plasma and
      quantitatively yielded 2. These results suggest that esterification of 2 with N,N
      dimethylglycine is a promising way for obtaining water-soluble prodrug forms of
      2. Based on the high susceptibility to liver esterase, the esters are potential
      prodrugs for achieving the site-specific delivery of 2.

PMID- 7724484
TI  - Stability of protein formulations: investigation of surfactant effects by a novel
      EPR spectroscopic technique.
AB  - Surfactants are known to stabilize proteins and are often employed as additives
      in protein formulations. We have developed a method to study the interaction of
      these formulation additives with proteins by using the partitioning behavior of a
      spin label. In protein-free formulations, 16-doxyl stearic acid partitions into
      micelles above the critical micelle concentration (CMC) of the surfactant and
      gives rise to composite electron paramagnetic resonance (EPR) spectra composed of
      spectra from "free" label and "rotationally hindered" label. We compute the
      fraction of micelle-associated label by factor analysis and generate a label
      partition curve. When protein is added to the formulation, surfactant-protein
      aggregates form at concentrations below the surfactant's CMC. Partitioning of the
      label into these aggregates causes the EPR spectrum to reflect hindered rotation
      of the label at lower surfactant concentrations than in the protein-free
      solutions. A simple model of label partitioning shows that these partitioning
      shifts can be correlated to the surfactant:protein binding stoichiometry. We have
      studied the interactions of various non-ionic surfactants like Brij and Tween
      with recombinant human growth hormone and recombinant human interferon-gamma and
      obtained corresponding binding stoichiometries. These binding stoichiometries
      match those obtained by other techniques. This technique offers a new method for
      estimating the protein:surfactant binding stoichiometries.

PMID- 7724485
TI  - Investigation of 3,5-isoxazolidinediones as hypolipidemic agents in rodents.
AB  - A series of 2-benzoyl-4,4-dialkyl-3,5-isoxazolidinediones proved to have potent
      hypolipidemic activity, lowering both serum cholesterol and triglyceride levels
      at 10 or 20 mg/kg/day, IP and orally in rodents. 2-(3,4,5-Trimethoxybenzoyl)-4,4
      diethyl-3,5-isoxazolidinedione+ ++ (4) afforded the best hypolipidemic activity
      lowering normolipidemic CF1 mouse serum cholesterol levels 49% and serum
      triglyceride levels 34% at 20 mg/kg/day, IP. Compound 4 was selected as a typical
      derivative of the chemical class for further detailed studies. Serum cholesterol
      levels in normolipidemic Sprague Dawley male rats were reduced 45% after 8 weeks
      at 10 and 20 mg/kg/day of compound, orally. Serum triglyceride levels were
      reduced 38-49% at 10 and 20 mg/kg/day, orally. In vitro liver enzyme activities
      studies in normolipidemic CF1 mice showed the compound inhibited mitochondrial
      citrate exchange, acetyl CoA synthetase, HMG CoA reductase, acyl CoA cholesterol
      acyl transferase, acetyl CoA carboxylase, sn-glycerol-3-phosphate acyl
      transferase, phosphatidylate phosphohydrolase and heparin-induced lipoprotein
      lipase activities with increases in the activities of cholesterol ester hydrolase
      and ATP-dependent citrate lyase. Similar enzyme activities were inhibited in vivo
      except HMG CoA reductase activity was not inhibited in rat liver or small
      intestinal mucosa after 8 weeks drug administration. Cholesterol levels were
      reduced in tissues after 8 weeks administration of compound 4 in normolipidemic
      rats. Bile cholesterol and triglyceride levels were elevated after two weeks
      administration to rats at 20 mg/kg/day. Serum lipoprotein levels in
      normolipidemic and hyperlipidemic rats showed the cholesterol levels in VLDL and
      LDL fractions after 4, 6 and 8 weeks at 10 and 20 mg/kg/day were reduced whereas
      HDL-cholesterol levels were significantly elevated. Studies demonstrated that 3H
      cholesterol and 14C-palmitic acid incorporation into lipids of the lipoprotein
      fraction was reduced by the drug but 32P-incorporation was generally elevated.
      The agent demonstrated no observable toxicity in rats after 8 weeks
      administration, orally. The acute toxicity study in normolipidemic mice at 20, 40
      and 100 mg/kg/day, IP, demonstrated no observable harmful effects of the drug.

PMID- 7724486
TI  - Structures of nanoparticles prepared from oil-in-water emulsions.
AB  - Hydrophobic substances were dissolved in an organic solvent and emulsified with
      an aqueous solution at very high shear. Droplets of very small sizes (50-100 nm)
      were obtained by using surfactants which were combinations of lecithins and bile
      salts. After emulsification, the organic solvent was removed by evaporation,
      yielding stable dispersions of solid particles. The sizes, shapes, and structures
      of the particles were examined through quasi-elastic light scattering, small
      angle neutron scattering and cryotransmission electron microscopy. Cholesterol
      acetate particles stabilized by lecithin and bile salts were found to be
      platelets of 10-20 nm thickness and 80 nm diameter. Cholesteryl acetate particles
      stabilized with POE-(20)-sorbitan monolaurate were dense spherical globules of
      diameter 100 nm. Particles with a composition similar to the endogenously
      occurring, lipoprotein, LDL, were large spherical globules studded with small
      vesicles. The subsequent evolution of the cholesteryl acetate dispersion upon
      aging was examined. There was no transfer of cholesteryl acetate between
      particles nor to large crystals. However, some aggregation of the particles was
      observed when the volume fraction of the particles in the aqueous dispersion
      exceeded 0.05. Thus, the structure of the nanoparticles obtained through
      deswelling of emulsion droplets changes according to the nature of the
      emulsifiers and to the composition of the hydrophobic substances which they
      contain.

PMID- 7724487
TI  - Rates of systemic degradation and reticuloendothelial system uptake of calcein in
      the dipalmitoylphosphatidylcholine liposomes with soybean-derived sterols in
      mice.
AB  - The systemic degradation and the reticuloendothelial system (RES) uptake of
      calcein entrapped in dipalmitoylphosphatidylcholine (DPPC) liposomes with soybean
      derived sterols (SS) were examined after intravenous administration to mice by
      measuring the free and liposomal calcein levels in the blood. The results
      indicate that the rates of systemic degradation and the RES uptake of liposomes
      decrease with the addition of SS in DPPC liposomes since the SS has the ability
      to stabilize the liposomes. The rate of uptake by RES is larger than the rate of
      systemic degradation. The rate of leakage of calcein from liposomes by incubation
      in plasma in vitro is almost the same as that of systemic degradation in vivo.

PMID- 7724488
TI  - Some factors associated with the ultrasonic nebulization of proteins.
AB  - Ultrasonic nebulization of lactate dehydrogenase (LDH) was investigated using a
      DeVilbiss "Aerosonic" nebulizer. The enzyme (8ml, 0.025 mg/ml Na2HPO4, pH 7.0)
      was completely inactivated after 20 minutes of operation. However, the
      inactivation profile observed during ultrasonic nebulization was different from
      that previously observed using air-jet nebulization. At least two mechanisms are
      involved, one associated with heating and the other with aerosol production. By
      preventing heating of the nebulizer fluid during operation, the denaturation
      profile was dramatically altered. By additionally including 0.01% w/v Tween 80 or
      1% w/v PEG 8000, almost all activity was retained. Similar results were obtained
      by preventing aerosol production and heating. However, 100% of activity was lost
      when heating was allowed to occur without aerosol formation. The results
      demonstrate that cooling in conjunction with a surfactant is one approach that
      could be used to stabilize proteins to ultrasonic nebulization. However, cooling
      also significantly reduced solute output from the nebulizer. When operated at 10
      degrees C output was negligible. At 50 degrees C the output was 5x greater than
      that found at room temperature. The median droplet size (micron(s)) was not
      significantly influenced by the operating temperature of the nebulizer fluid (3.6
      +/- 0.4, 21 degrees C; 3.9 +/- 0.2, 50 degrees C, p = NS (n = 6)) although the
      size distribution was noted to increase at the higher temperature.

PMID- 7724489
TI  - Reversible adsorption of soluble hexameric insulin onto the surface of insulin
      crystals cocrystallized with protamine: an electrostatic interaction.
AB  - Mixing pharmaceutical preparations of soluble neutral regular insulin solution
      (NRI) and neutral protamine Hagedorn (NPH) crystalline insulin suspension leads
      to a reduction in the measurable amount of soluble insulin in the formulation
      supernatant. However in spite of the loss in soluble insulin, the time-actions of
      these components have been shown, in clinical trials, to be unaffected. The
      interaction between these different physical forms of insulin has been studied
      using reversed-phase HPLC, isothermal titrating calorimetry, and Doppler
      electrophoretic light scattering analysis. Sorbent surface and solution
      perturbation studies revealed that the NRI adsorbs to the surface of the NPH
      crystal with an equilibrium constant ranging from 10(4) M-1 to 10(7) M-1,
      depending on the protamine concentration, pH, ionic strength, and temperature.
      This adsorption behavior suggests that the binding is mediated by electrostatic
      interactions arising between the positively-charged NPH crystal and the
      negatively-charged NRI hexamer. Doppler electrophoretic light scattering results,
      used to probe the pH-dependent surface charge of NPH and soluble insulin hexamer,
      support the conclusion that electrostatic interactions mediate the adsorption
      process. Adsorption studies under physiological conditions indicate that the
      elevated temperature and ionic strength, in a subcutaneous depot, are sufficient
      to lead to the dissociation of the NRI/NPH complex that exists in these NPH
      mixture formulations.

PMID- 7724490
TI  - Surface denaturation at solid-void interface--a possible pathway by which
      opalescent particulates form during the storage of lyophilized tissue-type
      plasminogen activator at high temperatures.
AB  - During protein lyophilization, it is common practice to complete the freezing
      step as fast as possible in order to avoid protein denaturation, as well as to
      obtain a final product of uniform quality. We report a contradictory observation
      made during lyophilization of recombinant tissue-type plasminogen activator (t
      PA) formulated in arginine. Fast cooling during lyophilization resulted in a
      lyophilized product that yielded more opalescent particulates upon long term
      storage at 50 degrees C, under a 150 mTorr nitrogen seal gas environment. Fast
      cooling also resulted in a lyophilized cake with a large internal surface area.
      Studies on lyophilized products containing 1% (w/w) residual moisture and varying
      cake surface areas (0.22-1.78 m2/gm) revealed that all lyophilized cakes were in
      an amorphous state with similar glass transition temperatures (103-105 degrees
      C). However, during storage the rate of opalescent particulate formation in the
      lyophilized product (as determined by UV optical density measurement in the 360
      to 340 nm range for the reconstituted solution) was proportional to the cake
      surface area. We suggest that this is a surface-related phenomenon in which the
      protein at the solid-void interface of the lyophilized cake denatures during
      storage at elevated temperatures. Irreversible denaturation at the ice-liquid
      interface during freezing in lyophilization is unlikely to occur, since repeated
      freezing/thawing did not show any adverse effect on the protein. Infrared
      spectroscopic analysis could not determine whether protein, upon lyophilization,
      at the solid-void interface would still be in a native form.

PMID- 7724491
TI  - Differential effects of sulfate and sulfobutyl ether of beta-cyclodextrin on
      erythrocyte membranes in vitro.
AB  - The hemolytic activity of beta-cyclodextrin (beta-CyD) on rabbit erythrocytes was
      reduced by the introduction of negatively-charged groups onto the hydroxyls of
      beta-CyD; the membrane disrupting abilities decreased in the order of beta-CyD >
      2-hydroxypropyl-beta-CyD (HP-beta-CyD) > sulfobutyl-beta-CyD (SB-beta-CyD) >>
      beta-CyD sulfate (S-beta-CyD). Under pre-hemolytic concentrations, both beta-CyD
      and SB-beta-CyD induced shape changes of membrane invagination on the
      erythrocytes. In sharp contrast, S-beta-CyD showed biphasic effect on the shape
      of the erythrocytes; i.e. the crenation at relatively low concentrations and the
      invagination at higher concentrations. The S-beta-CyD-induced membrane crenation
      arose from a direct action on the membranes rather than cell metabolism-mediated
      effects. Unlike beta-CyD, S-beta-CyD was found to bind to the erythrocytes and
      may be confined to the outer surface of the membrane bilayer, which may expand
      the exterior layer relative to the cytoplasmic half, thereby inducing the cells
      to crenate. On the other hand, the membrane invagination mediated by the three
      beta-CyDs was initiated by extracting specific membrane lipids from the cells,
      depending upon their inclusion abilities, subsequently leading to the lysis of
      the cells. These results indicate that SB-beta-CyD and S-beta-CyD interact with
      the erythrocyte membranes in a differential manner and possess lower membrane
      disrupting abilities than the parent beta-CyD and HP-beta-CyD.

PMID- 7724492
TI  - Acute renal toxicity of doxorubicin (adriamycin)-loaded cyanoacrylate
      nanoparticles.
AB  - Acute doxorubicin-loaded nanoparticle (DXNP) renal toxicity was explored in both
      normal rats and rats with experimental glomerulonephritis. In normal rats, 2/6
      rats given free doxorubicin (DX) (5 mg/kg) died within one week, whereas all
      control animals and all rats having received free NP or DXNP survived. A 3 times
      higher proteinuria appeared in animals treated with DXNP than in those treated
      with DX. Free NP did not provoke any proteinuria. Two hr post-injection, DXNP was
      2.7 times more concentrated in kidneys than free DX (p < 0.025). In rats with
      immune experimental glomerulonephritis, 5/6 rats given DX died within 7 days, in
      contrast to animals treated by DXNP, NP, or untreated, which all survived.
      Proteinuria appeared in all series, but was 2-5 times more intense (p > 0.001)
      and prolonged after doxorubicin treatment (400-700 mg/day), without significant
      difference between DXNP and DX. Rats treated by unloaded NP behaved as controls.
      These results demonstrate that, in these experimental conditions, DXNP killed
      less animals than free DX, despite of an enhanced renal toxicity of the former.
      Both effects (better survival and nephrosis) are most probably related to an
      enhanced capture of DXNP by cells of the mononuclear phagocyte system, including
      mesangial cells.

PMID- 7724493
TI  - A new method for estimating dermal absorption from chemical exposure: 2. Effect
      of molecular weight and octanol-water partitioning.
AB  - A new method for estimating dermal absorption including the effects of exposure
      time and chemistry is described generally in Part 1 of this series. This method
      accounts for the larger absorption rates during the initial exposure period as
      well as the hydrophilic barrier which the viable epidermis presents to lipophilic
      chemicals. A key parameter in this procedure, the ratio of the stratum corneum
      and epidermis permeabilities (B) depends on molecular weight and octanol-water
      partitioning. Several approaches for approximating B and its affect on the dermal
      absorption prediction are discussed here. Generally, the parameter B is only
      important for highly lipophilic chemicals which also have relatively small
      molecular weights. When B is important, the recommended prediction for B is based
      on the Potts and Guy correlation for human stratum corneum permeability.

PMID- 7724494
TI  - Aerosol deposition as a function of airway disease: cystic fibrosis.
AB  - A mathematical model of aerosol deposition has been developed for drug delivery
      protocols and used successfully to simulate inhalation exposure tests with human
      subjects. Therefore, we have used the validated model to address the delivery of
      inhaled pharmaceuticals as a function of disease-induced changes in airway
      structure. Clinical data from the literature had suggested that progressive lung
      disease associated with cystic fibrosis (CF) could compromise the successful
      administration of pharmacologic drugs used in its treatment, hence it was
      studied. We described the lungs of patients inflicted with CF by different
      morphologies (representing the processes of airway obstruction, infection and
      inflammation) than healthy (control) subjects. Affected ventilatory parameters
      were also examined to demonstrate their effects upon drug disposition. Particle
      distributions were computed on a generation-by-generation basis. Deposition
      patterns were dramatically affected by CF-produced alterations in dimensions. The
      reduced airway caliber in CF enhanced the total dose delivered to the
      tracheobronchial compartment by 200-300% relative to controls. The spatial
      distributions of aerosols were completely different in CF patients, being
      selectively deposited within congested airways. In medical practice the model can
      be tailored to any specific airway disease. Regarding targeted delivery, the
      results have relevance to (1) site-specific acting pharmaceuticals in
      tracheobronchial airways and (2) drugs designed for systemic delivery via
      deposition in alveolated airways.

PMID- 7724495
TI  - Nursing center at UND combined education with innovative health services to North
      Dakota.

PMID- 7724497
TI  - Senior info line.

PMID- 7724496
TI  - They said it couldn't be done.

PMID- 7724498
TI  - Medication assistants: a new chapter in North Dakota nursing.

PMID- 7724499
TI  - The workplace and you. Portable pensions.

PMID- 7724500
TI  - Self-reported risk behaviors and sexual behaviors in North Dakota high school
      juniors and seniors.

PMID- 7724501
TI  - The best prescription--humor in the workplace.

PMID- 7724502
TI  - [Chronic persistent cough: therapy].

PMID- 7724503
TI  - [Fatal pleural mesothelioma diseases caused by familial household contacts with
      asbestos fiber dust].
AB  - The case histories of a family are described where 3 out of 4 developed asbestos
      related diseases. Only the husband had direct occupational exposure handling blue
      asbestos materials while working in a producing insulating factory in 1950-59. He
      died of pulmonary asbestosis as an occupational disease. His wife and his son
      died of asbestos related mesothelioma. Detailed exposure history revealed
      exposure to asbestos by laundering her husband's contaminated working clothes.
      His son was exposed to asbestos during childhood by helping his mother laundering
      the father's working clothes and in addition by visiting his father's working
      place regularly. The significance of nonoccupational exposure to asbestos is
      emphasized as a causative factor in the development of malignant mesothelioma.

PMID- 7724504
TI  - [Drug monitoring: theophylline--comparison of 3 methods for determination].
AB  - Treatment with theophylline requires monitoring of dosage, preferably by
      determining the theophylline content in whole blood or serum, because
      theophylline pharmaco kinetics is most variable and therefore difficult to
      define, and because of possible interactions with other drugs. In medical
      practice, it is important and helpful to get the results of theophylline
      measurements quickly so that the dosage may be corrected directly whenever
      necessary. Two assays for rapid theophylline determination were compared with a
      standard method and with each other in respect of accuracy and practicability.
      Both methods a suitable for practical use.

PMID- 7724505
TI  - [Differential diagnostic significance of complex values of gas exchange during
      submaximal physical effort in patients with emphysema and pulmonary fibrosis].
AB  - The aim of this study was to clarify a) whether the behaviour of functional dead
      space ratio (VD/VE), alveolo-arterial difference of oxygen tensions (AaDO2) and
      the venous admixture ratio (QVA/Qt) differed at rest and during submaximal
      exercise, between patients with pulmonary emphysema and interstitial pulmonary
      fibrosis as well as from the respective findings in healthy controls, and b)
      whether a differentiation between these two diseases could be achieved by
      investigations of complex pulmonary gas exchange. Eleven patients with pulmonary
      fibrosis (F), which had been diagnosed by pulmonary biopsies, 11 patients with
      pulmonary emphysema (E) and 11 healthy controls (C) were subjected to
      conventional pulmonary function tests (PFTs: spirometry, bodyplethysmography,
      DCO) immediately followed by examinations of pulmonary gas exchange conducted at
      rest and during an incremental submaximal cycle spiroergometry (ERGO). With
      normal PFTs for C, vital capacity was diminished in F and the 1" timed vital
      capacity (FEV1) as well as Tiffeneau's index were reduced in E, while air way
      resistance and functional residual capacity were augmented in the latter group.
      In all patients the CO-diffusing capacity was lower compared to C, however,
      without differences between F and E. In both E and F, the arterial O2 tension
      were lower at rest as well as during ERGO when compared to C, whereas VD/VE,
      QVA/Qt and AaDO2 as well as the specific ventilation for O2 were higher,
      respectively. Alveolar ventilation was similar in all groups.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7724507
TI  - [Chronic course of eosinophilic pneumonia in infection with ascaris
      lumbricoides].
AB  - A case of ascariasis-associated Loeffler's pneumonia is reported, which presented
      like Carrington's chronic eosinophilic pneumonia (CEP). It is assumed, that under
      unfavourable conditions (children, old or disabled patients with high worm load)
      Loeffler's pneumonia takes a serious course, which can be confounded with CEP.

PMID- 7724506
TI  - [Ofloxacin-cycloserine-protionamide-INH combination against treatment refractory
      lung tuberculosis].
AB  - Multiresistant tuberculoses are on the increase. The conversion rates in
      "additional" therapy are only modest. 17 multiresistant patients and 6 treatment
      refractory tuberculoses were treated by us with ofloxacin-cycloserin-protionamide
      INH. 16 of these patients were HIV positive. 21 patients converted after 3 months
      of treatment by the latest. 3 patients died of HIV syndrome. There was otherwise
      no difference between HIV positive and HIV negative patients. As a rule, the
      combination was well tolerated. In multiresistant tuberculosis, it is mandatory
      to administer at least 3 drugs to which there is no resistance.

PMID- 7724508
TI  - Use of random amplified polymorphic DNA for identification of ruminant
      trichostrongylid nematodes.
AB  - The aim of this work was to evaluate random amplified polymorphic DNA (RAPD) as a
      source of markers for species identification and phylogenetic analysis of
      ruminant trichostrongylid nematodes. As these nematodes are often polymorphic,
      species identification may be difficult. We tested eight species and several of
      their morphs: Haemonchus contortus (three vulvar morphotypes: flap, smooth, and
      knobbed), Teladorsagia circumcincta, Ashworthius gagarini, Spiculopteragia
      boehmi, Ostertagia leptospicularis (and its morph Ostertagia kolchida), Cooperia
      oncophora (and its morph C. surnabada), Trichostrongylus colubriformis, and T.
      vitrinus. With five chosen 10-mer primers, genetic variations were assessed among
      individuals of each species or morphotype. In trichostrongylid nematodes, the
      identification of species is possible by means of RAPD on adult or larva DNA
      extracts, although the variability observed within species was very important for
      most species studied. The use of RAPD in phylogenetics studies is conversely
      questionable for this superfamily of parasitic nematodes. The interspecific
      distances were always larger than the intraspecific ones and did not vary much
      (between 0.8 and 0.9); they would not be of much use in the construction of a
      phylogenetic tree, at least for the species and the primers involved in this
      study.

PMID- 7724509
TI  - Effect of various doses of infective Toxocara canis and Toxocara cati eggs on the
      humoral response and distribution of larvae in mice.
AB  - The effect of 5-2,500 infective Toxocara canis and 5-1,000 T. cati eggs on the
      humoral immune response and on the distribution of larvae in the organism was
      studied in paratenic hosts--inbred C57BL6/J mice. With each dose of T. canis eggs
      the maximal antibody level was recorded on day 56 post infection and was followed
      by a moderate decline that lasted until day 154 of the experiment. A correlation
      between the antibody level and the egg count was observed only with the infective
      dose of 5-50 eggs. A more rapid occurrence of antibodies was recorded in mice
      infected with a high dose of eggs. In those given 5 and 7 T. cati eggs the
      antibody level exceeded the extinction threshold value only from day 21 to day
      84. Low doses of T. canis (n = 5) and T. cati (n = 7) eggs caused a comparable
      distribution of larvae in mice, and the larval recoveries on day 70 post
      infection ranged between 10.00% and 25.74%. Following a dose of 500 T. cati eggs,
      22.28% of the larvae were recovered, although only 1.08% were localized in the
      brain. A dose of 1,000 T. canis eggs yielded 36.37% of the larvae, with as much
      as 28.13% being found in the brain.

PMID- 7724510
TI  - Bovine cysticercosis: demonstration in experimentally infected calves of serum
      IgG antibodies reactive with neutral glycolipids of Taenia saginata and T.
      crassiceps metacestodes.
AB  - The immunoreactivity of Taenia saginata and T. crassiceps metacestode neutral
      glyco(sphingo)lipids towards IgG antibodies derived from the sera of calves with
      experimental cysticercosis has been established. The glyco(sphingo)lipids are
      separable by normal-phase HPTLC (high-performance thin-layer chromatography) into
      groups of increasing sugar-chain length (lipid/ceramide mono-, di-, tri-, tetra-
      and > tetrasaccharides), with those corresponding to three and four hexoses being
      the main immunoreactive components (HPTLC immunostaining). In ELISA (enzyme
      linked immunosorbent assay), reverse-phase HPTLC-isolated T. crassiceps
      metacestode glyco(sphingo)lipids equivalent to tri- and tetrahexoside allowed a
      discrimination between non-infected and infected calves (at least 80 metacestodes
      recovered). The formation of IgG antibodies was correlated with the infection,
      not with other non-specific inducing factors, as seen by the differential humoral
      response detected in experimentally infected (T. saginata) calves before and
      after Praziquantel treatment (HPTLC immunostaining and ELISA).

PMID- 7724511
TI  - A DNA fingerprinting method for individual characterization of Toxoplasma gondii
      strains: combination with isoenzymatic characters for determination of linkage
      groups.
AB  - The genetic polymorphism of Toxoplasma gondii was evaluated for 14 strains by
      isoenzyme and DNA analysis. The 14 strains belonged to 5 different zymodemes
      defined by the variable patterns of 6 enzyme systems. A restriction-fragment
      length polymorphism analysis was carried out with two endonucleases (Sal I and
      Pst I) and two repetitive probes (TGR1E and TGR6). This kind of repetitive probe
      allowed an individual identification of strain, with 13 schizodemes being
      observed among 14 strains. Only two strains were found to be totally identical
      when DNA and isoenzyme characters were considered. The numerical taxonomy methods
      applied to the results obtained for both types of characters allowed
      determination of linkage groups. Strain clustering obtained by numerical analysis
      of DNA characters alone is similar to the clustering obtained by analysis of
      isoenzyme and DNA characters together. A relationship was observed between the
      defined groups and virulence in Swiss mice.

PMID- 7724512
TI  - Transovarial transmission of Nosema locustae (Microsporida: Nosematidae) in the
      migratory locust Locusta migratoria migratorioides.
AB  - Nosema locustae, a microsporidian parasite of locusts and grasshoppers, was
      transovarially transmitted to the progeny of infected Locusta migratoria reared
      for up to F14 generations. The mortality of infected progeny in each generation
      was higher than that of uninfected controls and ranged from 67.6% to 95.5%.
      Infected female survivors transmitted the microsporidium to the progeny via eggs.
      The developing eggs harboured vegetative stages of N. locustae, and development
      of the microsporidium occurred during embryonation. Spores accumulated in the
      yolk and, after blastokinesis, both the yolk and the spores were enclosed in the
      midgut of the embryo. Germinated spores infected the functional midgut epithelium
      and invaded internal tissues. The mortality of newly hatched instars was high
      when embryonic tissue had been infected during development.

PMID- 7724513
TI  - Light and scanning electron microscopy of Echinostoma caproni (Trematoda) during
      maturation in ICR mice.
AB  - Light (LM) and scanning electron microscopy (SEM) were used to study the
      maturation of Echinostoma caproni in 13 ICR mice, each of which was exposed to 50
      encysted metacercariae and necropsied at 1-20 weeks postinfection (p.i.). All 13
      mice were infected with 20-30 worms/host and half the worms were used for LM and
      the remainder, for SEM. Body area measurements showed that the worms grew rapidly
      from day zero (excysted metacercariae) to 4 weeks p.i. and less rapidly
      thereafter. Area measurements of organs showed that the growth of the acetabular
      area paralleled that of the body. Gonadal area growth was less rapid than
      acetabular growth, and the area of the posterior testis was always greater than
      that of the anterior testis. The most remarkable change in topography occurred by
      5 weeks p.i. when some of the ventral tegumentary spines became multipointed with
      2-5 points/spine. Spine division was associated with a decline in worm growth,
      but the significance of this finding is unclear. Spine division probably
      facilitates the feeding, abrasion, and migration of this echinostome in the mouse
      small intestine.

PMID- 7724514
TI  - Erythrocytes carrying mutations in spectrin and protein 4.1 show differing
      sensitivities to invasion by Plasmodium falciparum.
AB  - The role of the erythrocyte skeleton in the invasion process of Plasmodium
      falciparum was evaluated using genetically variant erythrocytes containing well
      defined molecular defects in alpha spectrin (alpha Sp) or protein 4.1 from eight
      unrelated families. Invasion into red cells from subjects of three black families
      with hereditary pyropoikilocytosis (HPP) due to inheritance of alpha I/74 mutant
      spectrin was significantly reduced in cells both from the patients and from the
      relatives of these who carried asymptomatic hereditary elliptocytosis (HE).
      Likewise, reduced invasion was also seen in red cells from two families with HE
      in which the alpha I/65 variant spectrin was present. Resistance to invasion was
      not absolute in any sample and varied between 38% and 71% of that seen in normal
      cells. The decreased invasion correlated with the percentage of spectrin dimers
      present within the membrane of variant cells. In contrast, invasion into
      elliptocytes from three families that had a partial deficiency in protein 4.1
      (HE/4.1+) but a normal percentage of spectrin dimers was either unchanged or
      increased. The precise mechanism and molecular basis behind the reduced invasion
      into HPP and HE red cells bearing Sp alpha I domain variants remains to be
      elucidated but might relate to alterations in merozoite/red cell-receptor
      interactions and/or merozoite endocytosis. The occurrence of elliptocytosis with
      spectrin defects (in particular, Sp alpha I/65 and Sp alpha I/46 variants in West
      Africa) suggests that these mutations of the alpha Sp gene could be related to
      some protection against malaria.

PMID- 7724515
TI  - Negative tissue parasitism in mice injected with a noninfective clone of
      Trypanosoma cruzi.
AB  - Trypanosoma cruzi is a heterogeneous population of parasites as shown by
      differences between strains and cloned stock from the same strain. Herein we
      present evidence of the noninfectivity of CL-14, a clone derived from the CL
      strain of T. cruzi. In a previous paper we reported the absence of parasitemia
      and mortality in mice injected with metacyclic trypomastigotes of this clone. To
      investigate further this lack of infectivity we did and extensive
      histopathological analysis in mice at different intervals after i.p. (5 and 15
      days as well as 1, 4, and 12 months) or i.v. (5 and 30 days) injection of
      trypomastigotes. In spite of a systematic search in all tissues and organs of the
      animals, no parasite or significant pathological change was detected in any of
      the tissue sections. These data suggest the inability of this clone to mediate
      infection and/or cause pathological alterations in vivo.

PMID- 7724516
TI  - Light and electron microscopy studies on Onchocerca jakutensis and O. flexuosa of
      red deer show different host-parasite interactions.
AB  - Adult filariae of two intranodular Onchocerca species of red deer (Cervus
      elaphus) were examined at the ultrastructural level. In all, 90 nodules of O.
      flexuosa and 20 nodules of O. jakutensis were studied by histology. O. jakutensis
      caused cystic and pus-filled nodules in which the female and male worms were
      motile. Female worms possessed a thick cuticle and a well-developed somatic
      musculature. The basal lamina of the muscular syncytia was connected with the
      transhypodermal fibers through long protrusions. The epicuticle had only few
      protuberances and no visible surface coat. Female O. flexuosa showed
      morphological features similar to those of other intranodular filariae. A surface
      coat could not be detected. In 24% of 33 nodules with young live female worms and
      40% of 38 nodules with older live female O. flexuosa the worms were surrounded by
      giant cells apparently attacking a cuticle. This was found even in nodules
      obtained from animals no older than 9 months. It is probable that the lack of a
      surface coat protecting the female worm and the inability to move due to the
      reduced somatic muscles lead to an early elimination of O. flexuosa by the host's
      immune system.

PMID- 7724517
TI  - Pneumocystitis carinii organisms from in vitro culture are highly infectious to
      the nude rat.
AB  - Many in vitro systems have been used to cultivate Pneumocystis, but only limited
      parasite growth has been obtained by different authors. A reliable in vitro
      system enabling a sustained propagation of Pneumocystis appears to be an
      important condition for a better definition of the transmission of P. carinii
      pneumonia. In this work, Pneumocystis in vitro culture was performed on
      monolayers of L2 rat lung epithelial-like cells. Ultrastructural assessment
      revealed that culture parasites were structurally intact. Pneumocystis culture
      samples were intratracheally inoculated into corticosteroid-treated nude rats
      (nonlatently infected by P. carinii), which developed P. carinii pneumonia at 40
      days postinoculation. The infectious power of parasites obtained in vitro was 7
      10 times higher than that of parasites freshly extracted from parasitized rat
      lung. In summary, the present results show that it is possible to obtain in vitro
      highly infectious Pneumocystis forms, and this study provides a promising
      infectivity test for use by investigators working on Pneumocystis in vitro
      systems.

PMID- 7724518
TI  - Pollen-pistil interactions in compatible pollination.

PMID- 7724519
TI  - Natural killer cell receptors specific for major histocompatibility complex class
      I molecules.

PMID- 7724520
TI  - Pex1, a pollen-specific gene with an extensin-like domain.
AB  - We report here the identification of a pollen-specific gene from Zea mays that
      contains multiple Ser-(Pro)n repeats, the motif found in the cell wall-associated
      extensins. Sequence analysis reveals that the encoded protein has a putative
      globular domain at the N terminus and an extensin-like domain at the C terminus.
      The Pex1 (pollen extensin-like) gene is expressed exclusively in pollen, not in
      vegetative or female tissues, and is not induced in leaves upon wounding. We
      propose that the encoded protein may have a role in reproduction, either as a
      structural element deposited in the pollen tube wall during its rapid growth or
      as a sexual recognition molecule that interacts with partner molecules in the
      pistil.

PMID- 7724521
TI  - NMR of enzymatically synthesized uniformly 13C15N-labeled DNA oligonucleotides.
AB  - A procedure for the enzymatic synthesis of uniformly 13C15N-labeled DNA
      oligonucleotides in milligram quantities for NMR studies is described.
      Deoxynucleotides obtained from microorganisms grown on 13C and 15N nutrient
      sources are enzymatically phosphorylated to dNTPs, and the dNTPs are incorporated
      into oligonucleotides using a 3'-5' exonuclease-deficient mutant of Klenow
      fragment of DNA polymerase I and an oligonucleotide template primer designed for
      efficient separation of labeled product DNA from unlabeled template. The labeling
      strategy has been used to uniformly label one or the other oligonucleotide strand
      in the DNA duplex dGGCAAAACGG.dCCGTTTTGCC in order to facilitate assignment and
      structure determination by NMR. Application of 15N and 13C heteronuclear NMR
      experiments to isotopically labeled DNA is presented.

PMID- 7724522
TI  - High fat diet-induced hyperglycemia: prevention by low level expression of a
      glucose transporter (GLUT4) minigene in transgenic mice.
AB  - High-fat intake leading to obesity contributes to the development of non-insulin
      dependent diabetes mellitus (NIDDM, type 2). Similarly, mice fed a high-fat
      (safflower oil) diet develop defective glycemic control, hyperglycemia, and
      obesity. To assess the effect of a modest increase in the expression of GLUT4
      (the insulin-responsive glucose transporter) on impaired glycemic control caused
      by fat feeding, transgenic mice harboring a GLUT4 minigene were fed a high-fat
      diet. Low-level tissue-specific (heart, skeletal muscle, and adipose tissue)
      expression of the GLUT4 minigene in transgenic mice prevented the impairment of
      glycemic control and accompanying hyperglycemia, but not obesity, caused by fat
      feeding. Thus, a small increase (< or = 2-fold) in the tissue level of GLUT4
      prevents a primary symptom of the diabetic state in a mouse model, suggesting a
      possible target for intervention in the treatment of NIDDM.

PMID- 7724523
TI  - Stathmin interaction with a putative kinase and coiled-coil-forming protein
      domains.
AB  - Stathmin is a ubiquitous, cytosolic 19-kDa protein, which is phosphorylated on up
      to four sites in response to many regulatory signals within cells. Its molecular
      characterization indicates a functional organization including an N-terminal
      regulatory domain that bears the phosphorylation sites, linked to a putative
      alpha-helical binding domain predicted to participate in coiled-coil, protein
      protein interactions. We therefore proposed that stathmin may play the role of a
      relay integrating diverse intracellular regulatory pathways; its action on
      various target proteins would be a function of its combined phosphorylation
      state. To search for such target proteins, we used the two-hybrid screen in
      yeast, with stathmin as a "bait." We isolated and characterized four cDNAs
      encoding protein domains that interact with stathmin in vivo. One of the
      corresponding proteins was identified as BiP, a member of the hsp70 heat-shock
      protein family. Another is a previously unidentified, putative serine/threonine
      kinase, KIS, which might be regulated by stathmin or, more likely, be part of the
      kinases controlling its phosphorylation state. Finally, two clones code for
      subdomains of two proteins, CC1 and CC2, predicted to form alpha-helices
      participating in coiled-coil interacting structures. Their isolation by
      interaction screening further supports our model for the regulatory function of
      stathmin through coiled-coil interactions with diverse downstream targets via its
      presumed alpha-helical binding domain. The molecular and biological
      characterization of KIS, CC1, and CC2 proteins will give further insights into
      the molecular functions and mechanisms of action of stathmin as a relay of
      integrated intracellular regulatory pathways.

PMID- 7724524
TI  - The retinoblastoma-susceptibility gene product binds directly to the human TATA
      binding protein-associated factor TAFII250.
AB  - RB, the protein product of the retinoblastoma tumor-suppressor gene, regulates
      the activity of specific transcription factors. This regulation appears to be
      mediated either directly through interactions with specific transcription factors
      or through an alternative mechanism. Here we report that stimulation of Sp1
      mediated transcription by RB is partially abrogated at the nonpermissive
      temperature in ts13 cells. These cells contain a temperature-sensitive mutation
      in the TATA-binding protein-associated factor TAFII250, first identified as the
      cell cycle regulatory protein CCG1. The stimulation of Sp1-mediated transcription
      by RB in ts13 cells at the nonpermissive temperature could be restored by the
      introduction of wild-type human TAFII250. Furthermore, we demonstrate that RB
      binds directly to hTAFII250 in vitro and in vivo. These results suggest that RB
      can confer transcriptional regulation and possibly cell cycle control and tumor
      suppression through an interaction with TFIID, in particular with TAFII250.

PMID- 7724525
TI  - High incidence of XXY and XYY males among the offspring of female chimeras from
      embryonic stem cells.
AB  - Injecting male embryonic stem cells into the blastocoel of female embryos
      occasionally produces female chimeras capable of transmitting the embryonic stem
      cell genome. In our experiments several embryonic stem cell-derived male
      offspring from female chimeras were observed to be infertile. Karyotypic analysis
      of these infertile animals revealed aneuploidy. We examined the karyotypes of an
      additional 14 offspring not selected for infertility (3 females and 11 males)
      that had received the embryonic stem cell genome from 5 transmitting female
      chimeras. The 3 females and 5 of the males had normal karyotypes. Six of the
      males exhibited nonmosaic aneuploidy, which included four XXY karyotypes, one XYY
      karyotype, and an X,i(Y) karyotype. The high incidence of XXY and XYY males
      supports previous evidence for aberrant pairing and segregation of X and Y
      chromosomes when they are present in oocytes.

PMID- 7724526
TI  - Evolutionary importance for the membrane enhancement of the production of vitamin
      D3 in the skin of poikilothermic animals.
AB  - The photoproduction of vitamin D in the skin was essential for the evolutionary
      development of terrestrial vertebrates. During exposure to sunlight, previtamin
      D3 formed in the skin is isomerized to vitamin D3 (calciol) by a temperature
      dependent process. Since early land vertebrates were poikilothermic, the
      relatively slow conversion of previtamin D3 to vitamin D3 at ambient temperature
      put them at serious risk for developing vitamin D deficiency, thus leading to a
      poorly mineralized skeleton that could have ultimately halted further
      evolutionary development of vertebrates on land. We evaluated the rate of
      isomerization of previtamin D3 to vitamin D3 in the skin of iguanas and found the
      isomerization rate was enhanced by 1100% and 1700% at 25 degrees C and 5 degrees
      C, respectively. It is likely that the membrane entrapment of previtamin D3 in
      its s-cis,s-cis conformation is responsible for the markedly enhanced conversion
      of previtamin D3 to vitamin D3. The membrane-enhanced production of vitamin D3
      ensures the critical supply of vitamin D3 to poikilothermic animals such as
      iguanas.

PMID- 7724528
TI  - Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein.
AB  - The SSN6-TUP1 protein complex represses transcription of diversely regulated
      genes in the yeast Saccharomyces cerevisiae. Here we present evidence that MIG1,
      a zinc-finger protein in the EGR1/Zif268 family, recruits SSN6-TUP1 to glucose
      repressed promoters. DNA-bound LexA-MIG1 represses transcription of a target gene
      in glucose-grown cells, and repression requires SSN6 and TUP1. We also show that
      MIG1 and SSN6 fusion proteins interact in the two-hybrid system. Unexpectedly, we
      found that LexA-MIG1 activates transcription strongly in an ssn6 mutant and
      weakly in a tup1 mutant. Finally, LexA-MIG1 does not repress transcription in
      glucose-deprived cells, and MIG1 is differentially phosphorylated in response to
      glucose availability. We suggest a role for phosphorylation in regulating
      repression.

PMID- 7724527
TI  - Identification of the gene (SSU71/TFG1) encoding the largest subunit of
      transcription factor TFIIF as a suppressor of a TFIIB mutation in Saccharomyces
      cerevisiae.
AB  - Mutations in the Saccharomyces cerevisiae SSU71 gene were isolated as suppressors
      of a transcription factor TFIIB defect that confers both a cold-sensitive growth
      defect and a downstream shift in transcription start-site selection at the cyc1
      locus. The ssu71-1 suppressor not only suppresses the conditional phenotype but
      also restores the normal pattern of transcription initiation at cyc1. In
      addition, the ssu71-1 suppressor confers a heat-sensitive phenotype that is
      dependent upon the presence of the defective form of TFIIB. Molecular and genetic
      analysis of the cloned SSU71 gene demonstrated that SSU71 is a single-copy
      essential gene encoding a highly charged protein with a molecular mass of 82,194
      daltons. Comparison of the deduced Ssu71 amino acid sequence with the protein
      data banks revealed significant similarity to RAP74, the larger subunit of the
      human general transcription factor TFIIF. Moreover, Ssu71 is identical to p105, a
      component of yeast TFIIF. Taken together, these data demonstrate a functional
      interaction between TFIIB and the large subunit of TFIIF and that this
      interaction can affect start-site selection in vivo.

PMID- 7724529
TI  - Phenotypic knockout of the high-affinity human interleukin 2 receptor by
      intracellular single-chain antibodies against the alpha subunit of the receptor.
AB  - The experimental manipulation of peptide growth hormones and their cellular
      receptors is central to understanding the pathways governing cellular signaling
      and growth control. Previous work has shown that intracellular antibodies
      targeted to the endoplasmic reticulum (ER) can be used to capture specific
      proteins as they enter the ER, preventing their transport to the cell surface.
      Here we have used this technology to inhibit the cell surface expression of the
      alpha subunit of the high-affinity interleukin 2 receptor (IL-2R alpha). A single
      chain variable-region fragment of the anti-Tac monoclonal antibody was
      constructed with a signal peptide and a C-terminal ER retention signal.
      Intracellular expression of the single-chain antibody was found to completely
      abrogate cell surface expression of IL-2R alpha in stimulated Jurkat T cells. IL
      2R alpha was detectable within the Jurkat cells as an immature 40-kDa form that
      was sensitive to endoglycosidase H, consistent with its retention in a pre- or
      early Golgi compartment. A single-chain antibody lacking the ER retention signal
      was also able to inhibit cell surface expression of IL-2R alpha although the
      mechanism appeared to involve rapid degradation of the receptor chain within the
      ER. These intracellular antibodies will provide a valuable tool for examining the
      role of IL-2R alpha in T-cell activation, IL-2 signal transduction, and the
      deregulated growth of leukemic cells which overexpress IL-2R alpha.

PMID- 7724530
TI  - Switch from a type 2 to a type 1 T helper cell response and cure of established
      Leishmania major infection in mice is induced by combined therapy with
      interleukin 12 and Pentostam.
AB  - Successful treatment in allergic, autoimmune, and infectious diseases often
      requires altering the nature of a detrimental immune response mediated by a
      particular CD4+ T helper (Th) cell subset. While several factors contribute to
      the development of CD4+ Th1 and Th2 cells, the requirements for switching an
      established response are not understood. Here we use infection with Leishmania
      major as a model to investigate those requirements. We report that treatment with
      interleukin 12 (IL-12), in combination with the antimony-based leishmanicidal
      drug Pentostam, induces healing in L. major-infected mice and that healing is
      associated with a switch from a Th2 to a Th1 response. The data suggest that
      decreasing antigen levels may be required for IL-12 to inhibit a Th2 response and
      enhance a Th1 response. These observations are important for treatment of
      nonhealing forms of human leishmaniasis and also demonstrate that in a chronic
      infectious disease an inappropriate Th2 response can be switched to an effective
      Th1 response.

PMID- 7724531
TI  - A serine proteinase inhibitor locus at 18q21.3 contains a tandem duplication of
      the human squamous cell carcinoma antigen gene.
AB  - The squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin family of
      serine proteinase inhibitors (serpins). A neutral form of the protein is found in
      normal and some malignant squamous cells, whereas an acidic form is detected
      exclusively in tumor cells and in the circulation of patients with squamous cell
      tumors. In this report, we describe the cloning of the SCCA gene from normal
      genomic DNA. Surprisingly, two genes were found. They were tandemly arrayed and
      flanked by two other closely related serpins, plasminogen activator inhibitor
      type 2 (PAI2) and maspin at 18q21.3. The genomic structure of the two genes,
      SCCA1 and SCCA2, was highly conserved. The predicted amino acid sequences were
      92% identical and suggested that the neutral form of the protein was encoded by
      SCCA1 and the acidic form was encoded by SCCA2. Further characterization of the
      region should determine whether the differential expression of the SCCA genes
      plays a causal role in development of more aggressive squamous cell carcinomas.

PMID- 7724532
TI  - Induction of cell proliferation in mammalian inner-ear sensory epithelia by
      transforming growth factor alpha and epidermal growth factor.
AB  - Regenerative proliferation occurs in the inner-ear sensory epithelial of warm
      blooded vertebrates after insult. To determine how this proliferation is
      controlled in the mature mammalian inner ear, several growth factors were tested
      for effects on progenitor-cell division in cultured mouse vestibular sensory
      epithelia. Cell proliferation was induced in the sensory epithelium by
      transforming growth factor alpha (TGF-alpha) in a dose-dependent manner.
      Proliferation was also induced by epidermal growth factor (EGF) when supplemented
      with insulin, but not EGF alone. These observations suggest that stimulation of
      the EGF receptors by TGF-alpha binding, or EGF (plus insulin) binding, stimulates
      cell proliferation in the mature mammalian vestibular sensory epithelium.

PMID- 7724533
TI  - Quantitative measurement of intraorganelle pH in the endosomal-lysosomal pathway
      in neurons by using ratiometric imaging with pyranine.
AB  - Organelle acidification is an essential element of the endosomal-lysosomal
      pathway, but our understanding of the mechanisms underlying progression through
      this pathway has been hindered by the absence of adequate methods for quantifying
      intraorganelle pH. To address this problem in neurons, we developed a direct
      quantitative method for accurately determining the pH of endocytic organelles in
      live cells. In this report, we demonstrate that the ratiometric fluorescent pH
      indicator 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) is the most advantageous
      available probe for such pH measurements. To measure intraorganelle pH, cells
      were labeled by endocytic uptake of HPTS, the ratio of fluorescence emission
      intensities at excitation wavelengths of 450 nm and 405 nm (F450/405) was
      calculated for each organelle, and ratios were converted to pH values by using
      standard curves for F450/405 vs. pH. Proper calibration is critical for accurate
      measurement of pH values: standard curves generated in vitro yielded
      artifactually low organelle pH values. Calibration was unaffected by the use of
      culture medium buffered with various buffers or different cell types. By using
      this technique, we show that both acidic and neutral endocytically derived
      organelles exist in the axons of sympathetic neurons in different steady-state
      proportions than in the cell body. Furthermore, we demonstrate that these axonal
      organelles have a bimodal pH distribution, indicating a rapid acidification step
      in their maturation that reduces the average pH of a fraction of the organelles
      by 2 pH units while leaving few organelles of intermediate pH at steady state.
      Finally, we demonstrate a spatial gradient or organelle pH along axons, with the
      relative frequency of acidic organelles increasing with proximity to the cell
      body.

PMID- 7724534
TI  - Calcium sensing receptor: molecular cloning in rat and localization to nerve
      terminals.
AB  - We have molecularly cloned a calcium sensing receptor (CaSR) from a rat striatal
      cDNA library. Rat CaSR displays 92% overall homology to its bovine counterpart
      with seven putative transmembrane domains characteristic of the superfamily of
      guanine nucleotide-binding proteins and significant homology with the
      metabotropic glutamate receptors. Northern blot analysis reveals two transcripts
      in thyroid, kidney, lung, ileum, and pituitary. In brain highest regional
      expression of the RNA occurs in the hypothalamus and the corpus striatum.
      Immunohistochemistry reveals discrete punctate localizations throughout the brain
      that appear to be associated with nerve terminals. No staining is evident in cell
      bodies of neurons or glia. Cerebral arteries display an intense network of CaSR
      immunoreactive fibers associated with vessel innervation. CaSR on nerve terminal
      membranes may regulate neurotransmitter disposition in response to Ca2+ levels in
      the synaptic space.

PMID- 7724535
TI  - Loss of the catalytic subunit of the DNA-dependent protein kinase in DNA double
      strand-break-repair mutant mammalian cells.
AB  - The DNA-dependent protein kinase (DNA-PK) consists of three polypeptide
      components: Ku-70, Ku-80, and an approximately 350-kDa catalytic subunit (p350).
      The gene encoding the Ku-80 subunit is identical to the x-ray-sensitive group 5
      complementing gene XRCC5. Expression of the Ku-80 cDNA rescues both DNA double
      strand break (DSB) repair and V(D)J recombination in group 5 mutant cells. The
      involvement of Ku-80 in these processes suggests that the underlying defect in
      these mutant cells may be disruption of the DNA-PK holoenzyme. In this report we
      show that the p350 kinase subunit is deleted in cells derived from the severe
      combined immunodeficiency mouse and in the Chinese hamster ovary cell line V-3,
      both of which are defective in DSB repair and V(D)J recombination. A centromeric
      fragment of human chromosome 8 that complements the scid defect also restores
      p350 protein expression and rescues in vitro DNA-PK activity. These data suggest
      the scid gene may encode the p350 protein or regulate its expression and are
      consistent with a model whereby DNA-PK is a critical component of the DSB-repair
      pathway.

PMID- 7724536
TI  - Intersubunit contacts made by tryptophan 120 with biotin are essential for both
      strong biotin binding and biotin-induced tighter subunit association of
      streptavidin.
AB  - In natural streptavidin, tryptophan 120 of each subunit makes contacts with the
      biotin bound by an adjacent subunit through the dimer-dimer interface. To
      understand quantitatively the role of tryptophan 120 and its intersubunit
      communication in the properties of streptavidin, a streptavidin mutant in which
      tryptophan 120 is converted to phenylalanine was produced and characterized. The
      streptavidin mutant forms a tetrameric molecule and binds one biotin per subunit,
      as does natural streptavidin, indicating that the mutation of tryptophan 120 to
      phenylalanine has no significant effect on the basic properties of streptavidin.
      However, its biotin-binding affinity was reduced substantially, to approximately
      10(8) M-1, indicating that the contact made by tryptophan 120 to biotin has a
      considerable contribution to the extremely tight biotin binding by streptavidin.
      The mutant retained bound biotin over a wide pH range or with the addition of
      urea up to 6 M at neutral pH. However, bound biotin was efficiently released by
      the addition of excess free biotin due, presumably, to exchange reactions.
      Electrophoretic analysis revealed that the intersubunit contact made by
      tryptophan 120 to biotin through the dimer-dimer interface is the major
      interaction responsible for the biotin-induced, tighter subunit association of
      streptavidin. In addition, the mutant has weaker subunit association than natural
      streptavidin even in the absence of biotin, indicating that tryptophan 120 also
      contributes to the subunit association of tetramers in the absence of biotin.

PMID- 7724537
TI  - Residue replacements of buried aspartyl and related residues in sensory rhodopsin
      I: D201N produces inverted phototaxis signals.
AB  - Residue replacements were made at five positions (Arg-73, Asp-76, Tyr-87, Asp
      106, and Asp-201) in the Halobacterium salinarium phototaxis receptor sensory
      rhodopsin I (SR-I) by site-specific mutagenesis. The sites were chosen for their
      correspondence in position to residues of functional importance in the homologous
      light-driven proton pump bacteriorhodopsin found in the same organism. This work
      identifies a residue in SR-I shown to be of vital importance to its attractant
      signaling function: Asp-201. The effect of the substitution with the isosteric
      asparagine is to convert the normally attractant signal of orange light
      stimulation to a repellent signal. In contrast, similar neutral substitution of
      the four other ionizable residues near the photoactive site allows essentially
      normal attractant and repellent phototaxis signaling. Wild-type two-photon
      repellent signaling by the receptor is intact in the Asp-201 mutant, genetically
      separating the wild-type attractant and repellent signal generation processes. A
      possible explanation and implications of the inverted signaling are discussed.
      Results of neutral residue substitution for Asp-76 confirm our previous evidence
      that proton transfer reactions involving this residue are not important to
      phototaxis but that Asp-76 functions as the Schiff base proton acceptor in proton
      translocation by transducer-free SR-I.

PMID- 7724538
TI  - Computer determination of peptide conformations in water: different roads to
      structure.
AB  - Fragments of proteins (short peptides) that "fold" suggest a mechanism of how
      complete conformational search in protein folding is avoided. We used a
      computational method to determine structures of two foldable peptides in explicit
      water: RVEW and CSVTC. The optimization starts from random structures and no
      experimental constraints are used. In agreement with NMR data, the simulations
      find a hydrophobic pair (Val/Trp) in REVW. The structure of CSVTC is induced by a
      surface water that bridges two amide hydrogens, a drive to structure hypothesized
      by Ben-Naim [Ben-Naim, A. (1990) J. Chem. Phys. 93, 8196-8210] that is largely
      ignored in studies of folding. Tendency to structure in short peptide chains
      suggests a mechanism for the formation of short-range nucleation sites in protein
      folding.

PMID- 7724539
TI  - Sustained delivery of erythropoietin in mice by genetically modified skin
      fibroblasts.
AB  - We have examined whether the secretion of erythropoietin (Epo) from genetically
      modified cells could represent an alternative to repeated injections of the
      recombinant hormone for treating chronic anemias responsive to Epo. Primary mouse
      skin fibroblasts were transduced with a retroviral vector in which the murine Epo
      cDNA is expressed under the control of the murine phosphoglycerate kinase
      promoter. "Neo-organs" containing the genetically modified fibroblasts embedded
      into collagen lattices were implanted into the peritoneal cavity of mice.
      Increased hematocrit (> 80%) and elevated serum Epo concentration (ranging from
      60 to 408 milliunits/ml) were observed in recipient animals over a 10-month
      observation period. Hematocrit values measured in recipient mice varied according
      to the number of implanted Epo-secreting fibroblasts (ranging from 2.5 to 20 x
      10(6)). The implantation of neo-organs containing Epo-secreting fibroblasts
      appeared, therefore, as a convenient method to achieve permanent in vivo delivery
      of the hormone. We estimated that the biological efficacy of the approach may be
      relevant for the treatment of human hemoglobinopathies.

PMID- 7724540
TI  - In vivo assembly of rhodopsin from expressed polypeptide fragments.
AB  - Rhodopsin folding and assembly were investigated by expression of five bovine
      opsin gene fragments separated at points corresponding to proteolytic cleavage
      sites in the second or third cytoplasmic regions. The CH(1-146) and CH(147-348)
      gene fragments encode amino acids 1-146 and 147-348 of opsin, while the TH(1-240)
      and TH(241-348) gene fragments encode amino acids 1-240 and 241-348,
      respectively. Another gene fragment, CT(147-240), encodes amino acids 147-240.
      All five opsin polypeptide fragments were stably produced upon expression of the
      corresponding gene fragments in COS-1 cells. The singly expressed polypeptide
      fragments failed to form a chromophore with 11-cis-retinal, whereas coexpression
      of two or three complementary fragments [CH(1-146) + CH(147-348), TH(1-240) +
      TH(241-348), or CH(1-146) + CT(147-240) + TH(241-348)] formed pigments with
      spectral properties similar to wild-type rhodopsin. The NH2-terminal polypeptide
      in these rhodopsins showed a glycosylation pattern characteristic of wild-type
      COS-1 cell rhodopsin and was noncovalently associated with its complementary
      fragment(s). Further, the CH(1-146) + CH(147-348) rhodopsin showed substantial
      light-dependent activation of transducin. We conclude that the functional
      assembly of rhodopsin is mediated by the association of at least three protein
      folding domains.

PMID- 7724541
TI  - Crystallization and preliminary x-ray studies of NADPH-cytochrome P450 reductase.
AB  - NADPH-cytochrome P450 reductase (CPR; NADPH:ferrihemoprotein reductase, EC
      1.6.2.4) catalyzes the transfer of electrons to all known microsomal cytochromes
      P450. CPR is unique in that it is one of only two mammalian enzymes known to
      contain both flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN),
      the other being the various isoforms of nitric oxide synthase. Similarities in
      amino acid sequence and in functional domain arrangement with other key
      flavoproteins, including nitric oxide synthase, make CPR an excellent prototype
      for studies of interactions between two flavin cofactors. We have obtained
      diffraction-quality crystals of rat liver CPR, expressed in Escherichia coli and
      solubilized by limited proteolysis with trypsin. The crystals were grown in Hepes
      buffer (pH 7.0), containing polyethylene glycol 4500 and NaCl. The crystals
      belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell dimensions a
      = 103.3 A, b = 116.1 A, and c = 120.4 A. If we assume that there are two
      molecules of the 72-kDa CPR polypeptide per asymmetric unit, the calculated value
      of Vm is 2.54 A3/Da.

PMID- 7724542
TI  - Control of somite patterning by signals from the lateral plate.
AB  - The body musculature of higher vertebrates is composed of the epaxial muscles,
      associated with the vertebral column, and of the hypaxial muscles of the limbs
      and ventro-lateral body wall. Both sets of muscles arise from different cell
      populations within the dermomyotomal component of the somite. Myogenesis first
      occurs in the medial somitic cells that will form the epaxial muscles and starts
      with a significant delay in cells derived from the lateral somitic moiety that
      migrate to yield the hypaxial muscles. The newly formed somite is mostly composed
      of unspecified cells, and the determination of somitic compartments toward
      specific lineages is controlled by environmental cues. In this report, we show
      that determinant signals for lateral somite specification are provided by the
      lateral plate. They result in a blockade of the myogenic program, which maintains
      the lateral somitic cells as undifferentiated muscle progenitors expressing the
      Pax-3 gene, and represses the activation of the MyoD family genes. In vivo, this
      mechanism could account for the delay observed in the onset of myogenesis between
      muscles of the epaxial and hypaxial domains.

PMID- 7724543
TI  - p53-dependent growth arrest of REF52 cells containing newly amplified DNA.
AB  - The rat cell line REF52 is not permissive for gene amplification. Simian virus 40
      tumor (T) antigen converts these cells to a permissive state, as do dominant
      negative mutants of p53, suggesting that the effect of T antigen is due mainly to
      its ability to bind to p53. To manipulate permissivity, we introduced a
      temperature-sensitive mutant of T antigen (tsA58) into REF52 cells and selected
      for resistance to N-(phosphonacetyl)-L-aspartate (PALA). Most freshly isolated
      PALA-resistant colonies, each of approximately 200 cells, selected at a
      permissive temperature, arrested when shifted to a nonpermissive temperature.
      Growth arrest was stable, with no evidence of apoptosis, as long as T antigen was
      absent but was reversed when T antigen was restored. In contrast, PALA-resistant
      clones grown to approximately 10(7) cells at a permissive temperature did not
      arrest when shifted to a nonpermissive temperature. All PALA-resistant clones
      examined had amplified carbamoyl-phosphate synthetase-aspartate transcarbamoylase
      dihydroorotase (CAD) genes, present in structures consistent with a mechanism
      involving bridge-breakage-fusion (BBF) cycles. We propose that p53-mediated
      growth arrest operates only early during the complex process of gene
      amplification, when newly formed PALA-resistant cells contain broken DNA,
      generated in BBF cycles. During propagation under permissive conditions, the
      broken DNA ends are healed, and, even though the p53-mediated pathway is still
      intact at a nonpermissive temperature and the cells contain amplified DNA, they
      are not arrested in the absence of broken DNA. The data support the hypothesis
      that BBF cycles are an important mechanism of amplification and that the broken
      DNA generated in each cycle is a key signal that regulates permissivity for gene
      amplification.

PMID- 7724544
TI  - Non-clathrin-coat protein alpha is a conserved subunit of coatomer and in
      Saccharomyces cerevisiae is essential for growth.
AB  - To complete the molecular characterization of coatomer, the preformed cytosolic
      complex that is involved in the formation of biosynthetic transport vesicles, we
      have cloned and characterized the gene for non-clathrin-coat protein alpha (alpha
      COP) from Saccharomyces cerevisiae. The derived protein, molecular weight of
      135,500, contains four WD-40 repeated motifs (Trp/Asp-containing motifs of
      approximately 40 amino acids). Disruption of the yeast alpha-COP gene is lethal.
      Comparison of the DNA-derived primary structure with peptides from bovine alpha
      COP shows a striking homology. alpha-COP is localized to coated transport
      vesicles and coated buds of Golgi membranes derived from CHO cells.

PMID- 7724546
TI  - Calmodulin is a selective mediator of Ca(2+)-induced Ca2+ release via the
      ryanodine receptor-like Ca2+ channel triggered by cyclic ADP-ribose.
AB  - The ryanodine receptor-like Ca2+ channel (RyRLC) is responsible for Ca2+ wave
      propagation and Ca2+ oscillations in certain nonmuscle cells by a Ca(2+)-induced
      Ca2+ release (CICR) mechanism. Cyclic ADP-ribose (cADPR), an enzymatic product
      derived from NAD+, is the only known endogenous metabolite that acts as an
      agonist on the RyRLC. However, the mode of action of cADPR is not clear. We have
      identified calmodulin as a functional mediator of cADPR-triggered CICR through
      the RyRLC in sea urchin eggs. cADPR-induced Ca2+ release consisted of two phases,
      an initial rapid release phase and a subsequent slower release. The second phase
      was selectively potentiated by calmodulin which, in turn, was activated by Ca2+
      released during the initial phase. Caffeine enhanced the action of calmodulin.
      Calmodulin did not play a role in inositol 1,4,5-trisphosphate-induced Ca2+
      release. These findings offer insights into the multiple pathways that regulate
      intracellular Ca2+ signaling.

PMID- 7724545
TI  - Overexpression of the c-Myc oncoprotein blocks the growth-inhibitory response but
      is required for the mitogenic effects of transforming growth factor beta 1.
AB  - One of the more intriguing aspects of transforming growth factor beta 1 (TGF beta
      1) is its ability to function as both a mitogenic factor for certain mesenchymal
      cells and a potent growth inhibitor of lymphoid, endothelial, and epithelial
      cells. Data are presented indicating that c-myc may play a pivotal role in both
      the mitogenic and antiproliferative actions of TGF beta 1. In agreement with
      previous studies using C3H/10T1/2 fibroblasts constitutively expressing an
      exogenous c-myc cDNA, we show that AKR-2B fibroblasts expressing a chimeric
      estrogen-inducible form of c-myc (mycER) are able to form colonies in soft agar
      in the presence of TGF beta 1 only when c-myc is activated by hormone. Whereas
      these findings support a synergistic role for c-myc in mitogenic responses to TGF
      beta 1, we also find that c-myc can antagonize the growth-inhibitory response to
      TGF beta 1. Mouse keratinocytes (BALB/MK), which are normally growth-arrested by
      TGF beta 1, are rendered insensitive to the growth-inhibitory effects of TGF beta
      1 upon mycER activation. This ability of mycER activation to block TGF beta 1
      induced growth arrest was found to occur only when the fusion protein was induced
      with hormone in the early part of G1. Addition of estradiol late in G1 had no
      suppressive effect on TGF beta 1-induced growth inhibition.

PMID- 7724547
TI  - Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase
      among patients with autosomal recessive retinitis pigmentosa.
AB  - Mutations in the gene encoding the beta subunit of rod cGMP phosphodiesterase are
      known causes of photoreceptor degeneration in two animal models of retinitis
      pigmentosa, the rd (retinal degeneration) mouse and the Irish setter dog with
      rod/cone dysplasia. Here we report a screen of 92 unrelated patients with
      autosomal recessive retinitis pigmentosa for defects in the human homologue of
      this gene. We identified seven different mutations that cosegregate with the
      disease. They were found among four patients with each patient heterozygously
      carrying two mutations. All of these mutations are predicted to affect the
      putative catalytic domain, probably leading to a decrease in phosphodiesterase
      activity and an increase in cGMP levels within rod photoreceptors. Mutations in
      the gene encoding the beta subunit of rod phosphodiesterase are the most common
      identified cause of autosomal recessive retinitis pigmentosa, accounting for
      approximately 4% of cases in North America.

PMID- 7724548
TI  - Two routes of chlorophyllide synthesis that are differentially regulated by light
      in barley (Hordeum vulgare L.).
AB  - NADPH-protochlorophyllide oxidoreductase (POR; EC 1.6.99.1) catalyzes the only
      known light-dependent step in chlorophyll synthesis of higher plants, the
      reduction of protochlorophyllide (Pchlide) to chlorophyllide. In barley, two
      distinct immunoreactive POR proteins were identified. In contrast to the light
      sensitive POR enzyme studied thus far (POR-A), levels of the second POR protein
      remained constant in seedlings during the transition from dark growth to the
      light and in green plants. The existence of a second POR-related protein was
      verified by isolating and sequencing cDNAs that encode a second POR polypeptide
      (POR-B) with an amino acid sequence identity of 75% to the POR-A. In the presence
      of NADPH and Pchlide, the in vitro-synthesized POR-A and POR-B proteins could be
      reconstituted to ternary enzymatically active complexes that reduced Pchlide to
      chlorophyllide only after illumination. Even though the in vitro activities of
      the two enzymes were similar, the expression of their genes during the light
      induced transformation of etiolated to green seedlings was distinct. While the
      POR-A mRNA rapidly declined during illumination of dark-grown seedlings and soon
      disappeared, POR-B mRNA remained at an approximately constant level in dark-grown
      and green seedlings. Thus these results suggest that chlorophyll synthesis is
      controlled by two light-dependent POR enzymes, one that is active only
      transiently in etiolated seedlings at the beginning of illumination and the other
      that also operates in green plants.

PMID- 7724549
TI  - The 62- and 80-kDa subunits of transcription factor IIH mediate the interaction
      with Epstein-Barr virus nuclear protein 2.
AB  - EBNA 2 (Epstein-Barr virus nuclear antigen 2) is an acidic transactivator
      essential for EBV transformation of B lymphocytes. We show that EBNA 2 directly
      interacts with general transcription factor IIH. Glutathione S-transferase (GST)
      EBNA 2 acidic domain fusion protein depleted transcription factor IIH activity
      from a TFIIH nuclear fraction. The p89 (ERCC3), p80 (ERCC2), and p62 subunits of
      TFIIH were among the proteins retained by GST-EBNA 2. Eluates from the GST-EBNA 2
      beads reconstituted activity in a TFIIH-dependent in vitro transcription assay.
      The p62 and p80 subunits of TFIIH independently bound to GST-EBNA 2, whereas the
      p34 subunit of TFIIH only bound in the presence of p62. A Trp-->Thr mutation in
      the EBNA 2 acidic domain abolishes EBNA 2 transactivation in vivo and greatly
      compromised EBNA 2 association with TFIIH activity and with the p62 and p80
      subunits, providing a link between EBNA 2 transactivation and these interactions.
      Antibodies directed against the p62 subunit of TFIIH coimmunoprecipitated EBNA 2
      from EBV-transformed B lymphocytes, indicating that EBNA 2 associates with TFIIH
      in vivo.

PMID- 7724550
TI  - Reconstitution of p53-ubiquitinylation reactions from purified components: the
      role of human ubiquitin-conjugating enzyme UBC4 and E6-associated protein (E6AP).
AB  - The E6 protein of the high-risk human papillomaviruses inactivates the tumor
      suppressor protein p53 by stimulating its ubiquitinylation and subsequent
      degradation. Ubiquitinylation is a multistep process involving a ubiquitin
      activating enzyme, one of many distinct ubiquitin-conjugating enzymes, and in
      certain cases, a ubiquitin ligase. In human papillomavirus-infected cells, E6 and
      the E6-associated protein are thought to act as a ubiquitin-protein ligase in the
      ubiquitinylation of p53. Here we describe the cloning of a human ubiquitin
      conjugating enzyme that specifically ubiquitinylates E6-associated protein.
      Furthermore, we define the biochemical pathway of p53 ubiquitinylation and
      demonstrate that in vivo inhibition of various components in the pathway leads to
      an inhibition of E6-stimulated p53 degradation.

PMID- 7724551
TI  - Addiction protein Phd of plasmid prophage P1 is a substrate of the ClpXP serine
      protease of Escherichia coli.
AB  - Plasmid-encoded addiction genes augment the apparent stability of various low
      copy number bacterial plasmids by selectively killing plasmid-free (cured)
      segregants or their progeny. The addiction module of plasmid prophage P1 consists
      of a pair of genes called phd and doc. Phd serves to prevent host death when the
      prophage is retained and, should retention mechanisms fail, Doc causes death on
      curing. Doc acts as a cell toxin to which Phd is an antidote. In this study we
      show that host mutants with defects in either subunit of the ClpXP protease
      survive the loss of a plasmid that contains a P1 addiction module. The small
      antidote protein Phd is fully stable in these two mutant hosts, whereas it is
      labile in a wild-type host. We conclude that the role of ClpXP in the addiction
      mechanism of P1 is to degrade the Phd protein. This conclusion situates P1 among
      plasmids that elicit severe withdrawal symptoms and are able to do so because
      they encode both a cell toxin and an actively degraded macromolecule that blocks
      the synthesis or function of the toxin.

PMID- 7724552
TI  - Prolactin-immunoglobulin G complexes from human serum act as costimulatory
      ligands causing proliferation of malignant B lymphocytes.
AB  - Several lines of evidence indicate that immunoglobulin-bound prolactin found in
      human serum is not a conventional complex between an anti-prolactin antibody and
      prolactin but a different type of association of prolactin with the Fab portion
      of IgG heavy chains. The complex of prolactin with IgG was purified from serum by
      anti-human prolactin affinity chromatography and was shown to contain close to 1
      mole of N epsilon-(gamma-glutamyl)lysine crosslinks per mole of complex, a
      characteristic feature in structures crosslinked by transglutaminase.
      Interestingly, the complex caused a proliferation of cells from a subset of
      patients with chronic lymphocytic leukemia, while it was inactive in a cell
      proliferation prolactin bioassay. By contrast, human prolactin stimulated the
      proliferation of cells in the bioassay but had no effect on the complex
      responsive cells from the patients. Competition studies with prolactin and free
      Fc fragment of IgG demonstrated a necessity for engaging both the prolactin and
      the immunoglobulin receptors for proliferation. More importantly, competition for
      the growth response by free prolactin and IgG suggests both possible reasons for
      the slow growth of this neoplasm as well as avenues for control of the disease.

PMID- 7724554
TI  - A sampling problem in molecular dynamics simulations of macromolecules.
AB  - Correlations in low-frequency atomic displacements predicted by molecular
      dynamics simulations on the order of 1 ns are undersampled for the time scales
      currently accessible by the technique. This is shown with three different
      representations of the fluctuations in a macromolecule: the reciprocal space of
      crystallography using diffuse x-ray scattering data, real three-dimensional
      Cartesian space using covariance matrices of the atomic displacements, and the 3N
      dimensional configuration space of the protein using dimensionally reduced
      projections to visualize the extent to which phase space is sampled.

PMID- 7724553
TI  - Inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine on visna virus infection
      in lambs: a model for in vivo testing of candidate anti-human immunodeficiency
      virus drugs.
AB  - The acyclic nucleoside phosphonate analog 9-(2-phosphonylmethoxyethyl)adenine
      (PMEA) was recently found to be effective as an inhibitor of visna virus
      replication and cytopathic effect in sheep choroid plexus cultures. To study
      whether PMEA also affects visna virus infection in sheep, two groups of four
      lambs each were inoculated intracerebrally with 10(6.3) TCID50 of visna virus
      strain KV1772 and treated subcutaneously three times a week with PMEA at 10 and
      25 mg/kg, respectively. The treatment was begun on the day of virus inoculation
      and continued for 6 weeks. A group of four lambs were infected in the same way
      but were not treated. The lambs were bled weekly or biweekly and the leukocytes
      were tested for virus. At 7 weeks after infection, the animals were sacrificed,
      and cerebrospinal fluid (CSF) and samples of tissue from various areas of the
      brain and from lungs, spleen, and lymph nodes were collected for isolation of
      virus and for histopathologic examination. The PMEA treatment had a striking
      effect on visna virus infection, which was similar for both doses of the drug.
      Thus, the frequency of virus isolations was much lower in PMEA-treated than in
      untreated lambs. The difference was particularly pronounced in the blood, CSF,
      and brain tissue. Furthermore, CSF cell counts were much lower and inflammatory
      lesions in the brain were much less severe in the treated lambs than in the
      untreated controls. The results indicate that PMEA inhibits the propagation and
      spread of visna virus in infected lambs and prevents brain lesions, at least
      during early infection. The drug caused no noticeable side effects during the 6
      weeks of treatment.

PMID- 7724555
TI  - Gene therapy for diabetes mellitus in rats by hepatic expression of insulin.
AB  - Type 1 diabetes mellitus is caused by severe insulin deficiency secondary to the
      autoimmune destruction of pancreatic beta cells. Patients need to be controlled
      by periodic insulin injections to prevent the development of ketoacidosis, which
      can be fatal. Sustained, low-level expression of the rat insulin 1 gene from the
      liver of severely diabetic rats was achieved by in vivo administration of a
      recombinant retroviral vector. Ketoacidosis was prevented and the treated animals
      exhibited normoglycemia during a 24-hr fast, with no evidence of hypoglycemia.
      Histopathological examination of the liver in the treated animals showed no
      apparent abnormalities. Thus, the liver is an excellent target organ for ectopic
      expression of the insulin gene as a potential treatment modality for type 1
      diabetes mellitus by gene therapy.

PMID- 7724556
TI  - Protein structure-based design of potent orally bioavailable, nonpeptide
      inhibitors of human immunodeficiency virus protease.
AB  - A class of potent nonpeptidic inhibitors of human immunodeficiency virus protease
      has been designed by using the three-dimensional structure of the enzyme as a
      guide. By employing iterative protein cocrystal structure analysis, design, and
      synthesis the binding affinity of the lead compound was incrementally improved by
      over four orders of magnitude. An inversion in inhibitor binding mode was
      observed crystallographically, providing information critical for subsequent
      design and highlighting the utility of structural feedback in inhibitor
      optimization. These inhibitors are selective for the viral protease enzyme,
      possess good antiviral activity, and are orally available in three species.

PMID- 7724558
TI  - Interfacial activation-based molecular bioimprinting of lipolytic enzymes.
AB  - Interfacial activation-based molecular (bio)-imprinting (IAMI) has been developed
      to rationally improve the performance of lipolytic enzymes in nonaqueous
      environments. The strategy combinedly exploits (i) the known dramatic enhancement
      of the protein conformational rigidity in a water-restricted milieu and (ii) the
      reported conformational changes associated with the activation of these enzymes
      at lipid-water interfaces, which basically involves an increased substrate
      accessibility to the active site and/or an induction of a more competent
      catalytic machinery. Six model enzymes have been assayed in several model
      reactions in nonaqueous media. The results, rationalized in light of the present
      biochemical and structural knowledge, show that the IAMI approach represents a
      straightforward, versatile method to generate manageable, activated (kinetically
      trapped) forms of lipolytic enzymes, providing under optimal conditions
      nonaqueous rate enhancements of up to two orders of magnitude. It is also shown
      that imprintability of lipolytic enzymes depends not only on the nature of the
      enzyme but also on the "quality" of the interface used as the template.

PMID- 7724557
TI  - Extracellular pH regulation in microdomains of colonic crypts: effects of short
      chain fatty acids.
AB  - It has been suggested that transepithelial gradients of short-chain fatty acids
      (SCFAs; the major anions in the colonic lumen) generate pH gradients across the
      colonic epithelium. Quantitative confocal microscopy was used to study
      extracellular pH in mouse distal colon with intact epithelial architecture, by
      superfusing tissue with carboxy SNARF-1 (a pH-sensitive fluorescent dye). Results
      demonstrate extracellular pH regulation in two separate microdomains surrounding
      colonic crypts: the crypt lumen and the subepithelial tissue adjacent to crypt
      colonocytes. Apical superfusion with (i) a poorly metabolized SCFA (isobutyrate),
      (ii) an avidly metabolized SCFA (n-butyrate), or (iii) a physiologic mixture of
      acetate/propionate/n-butyrate produced similar results: alkalinization of the
      crypt lumen and acidification of subepithelial tissue. Effects were (i) dependent
      on the presence and orientation of a transepithelial SCFA gradient, (ii) not
      observed with gluconate substitution, and (iii) required activation of sustained
      vectorial acid/base transport by SCFAs. Results suggest that the crypt lumen
      functions as a pH microdomain due to slow mixing with bulk superfusates and that
      crypts contribute significant buffering capacity to the lumen. In conclusion,
      physiologic SCFA gradients cause polarized extracellular pH regulation because
      epithelial architecture and vectorial transport synergize to establish regulated
      microenvironments.

PMID- 7724559
TI  - Human general transcription factor TFIIA: characterization of a cDNA encoding the
      small subunit and requirement for basal and activated transcription.
AB  - The human general transcription factor TFIIA is one of several factors involved
      in specific transcription by RNA polymerase II, possibly by regulating the
      activity of the TATA-binding subunit (TBP) of TFIID. TFIIA purified from HeLa
      extracts consists of 35-, 19-, and 12-kDa subunits. Here we describe the
      isolation of a cDNA clone (hTFIIA gamma) encoding the 12-kDa subunit. Using
      expression constructs derived from hTFIIA gamma and TFIIA alpha/beta (which
      encodes a 55-kDa precursor to the alpha and beta subunits of natural TFIIA), we
      have constructed a synthetic TFIIA with a polypeptide composition similar to that
      of natural TFIIA. The recombinant complex supports the formation of a DNA-TBP
      TFIIA complex and mediates both basal and Gal4-VP16-activated transcription by
      RNA polymerase II in TFIIA-depleted nuclear extracts. In contrast, TFIIA has no
      effect on tRNA and 5S RNA transcription by RNA polymerase III in this system. We
      also present evidence that both the p55 and p12 recombinant subunits interact
      with TBP and that the basic region of TBP is critical for the TFIIA-dependent
      function of TBP in nuclear extracts.

PMID- 7724560
TI  - Delivery of antisense oligodeoxyribonucleotides against the human epidermal
      growth factor receptor into cultured KB cells with liposomes conjugated to folate
      via polyethylene glycol.
AB  - Antisense oligodeoxyribonucleotides targeted to the epidermal growth factor (EGF)
      receptor were encapsulated into liposomes linked to folate via a polyethylene
      glycol spacer (folate-PEG-liposomes) and efficiently delivered into cultured KB
      cells via folate receptor-mediated endocytosis. The oligonucleotides were a
      phosphodiester 15-mer antisense to the EGF receptor (EGFR) gene stop codon
      (AEGFR2), the same sequence with three phosphorothioate linkages at each terminus
      (AEGFR2S), a randomized 15-mer control of similar base composition to AEGFR2
      (RC15), a 14-mer control derived from a symmetrized Escherichia coli lac operator
      (LACM), and the 5'-fluorescein-labeled homologs of several of the above. Cellular
      uptake of AEGFR2 encapsulated in folate-PEG-liposomes was nine times higher than
      AEGFR2 encapsulated in nontargeted liposomes and 16 times higher than
      unencapsulated AEGFR2. Treatment of KB cells with AEGFR2 in folate-PEG-liposomes
      resulted in growth inhibition and significant morphological changes. Curiously,
      AEGFR2 and AEGFR2S encapsulated in folate-PEG-liposomes exhibited virtually
      identical growth inhibitory effects, reducing KB cell proliferation by > 90% 48
      hr after the cells were treated for 4 hr with 3 microM oligonucleotide. Free
      AEGFR2 caused almost no growth inhibition, whereas free AEGFR2S was only one
      fifth as potent as the folate-PEG-liposome-encapsulated oligonucleotide. Growth
      inhibition of the oligonucleotide-treated cells was probably due to reduced EGFR
      expression because indirect immunofluorescence staining of the cells with a
      monoclonal antibody against the EGFR showed an almost quantitative reduction of
      the EGFR in cells treated with folate-PEG-liposome-entrapped AEGFR2. These
      results suggest that antisense oligonucleotide encapsulation in folate-PEG
      liposomes promise efficient and tumor-specific delivery and that phosphorothioate
      oligonucleotides appear to offer no major advantage over native phosphodiester
      DNA when delivered by this route.

PMID- 7724561
TI  - Disaccharide uptake and priming in animal cells: inhibition of sialyl Lewis X by
      acetylated Gal beta 1-->4GlcNAc beta-O-naphthalenemethanol.
AB  - Inhibitors of glycosylation provide a tool for studying the biology of
      glycoconjugates. One class of inhibitors consists of glycosides that block
      glycoconjugate synthesis by acting as primers of free oligosaccharide chains. A
      typical primer contains one sugar linked to a hydrophobic aglycone. In this
      report, we describe a way to use disaccharides as primers. Chinese hamster ovary
      cells readily take up glycosides containing a pentose linked to naphthol, but
      they take up hexosides less efficiently and disaccharides not at all. Linking
      phenanthrol to a hexose improves its uptake dramatically but has no effect on
      disaccharides. To circumvent this problem, analogs of Xyl beta 1-->6Gal beta-O-2
      naphthol were tested as primers of glycosaminoglycan chains. The unmodified
      disaccharide did not prime, but methylated derivatives had activity in the order
      Xyl beta 1-->6Gal(Me)3-beta-O-2-naphthol > Xyl beta 1-->6Gal (Me)2 beta-O-2
      naphthol >> Xyl beta 1-->6Gal(Me)beta-O-2-naphthol. Acetylated Xyl beta 1-->6Gal
      beta-O-2-naphthol also primed glycosaminoglycans efficiently, suggesting that the
      terminal xylose residue was exposed by removing the acetyl groups. The general
      utility of using acetyl groups to create disaccharide primers was shown by the
      priming of oligosaccharides on peracetylated Gal beta 1-->4GlcNAc beta-O
      naphthalenemethanol. This disaccharide inhibited sialyl Lewis X expression on HL
      60 cells.

PMID- 7724562
TI  - The Ran/TC4 GTPase-binding domain: identification by expression cloning and
      characterization of a conserved sequence motif.
AB  - Ran/TC4 is an essential, nuclear GTPase implicated in the initiation of DNA
      replication, entry into and exit from mitosis, and in nuclear RNA and protein
      transport through the nuclear pore complex. This diversity of functions suggests
      that Ran interacts with a large number of down-stream targets. Using an overlay
      assay, we detected a family of putative target proteins that associate with GTP
      bound Ran. The sequence of only one such protein, HTF9a/RanBP1, is known. We have
      now cloned two additional Ran-binding proteins, allowing identification of a
      distinctive, highly conserved sequence motif of approximately 150 residues. This
      motif represents a minimal Ran-binding domain that stabilizes the GTP-bound state
      of Ran. The isolated domain also functions as a coactivator of Ran-GTPase
      activating protein. Mutation of a conserved residue within the Ran-binding domain
      of HTF9a protein drastically reduced Ran binding. Ran-binding proteins
      coimmunoprecipitated with epitope-tagged Ran from cell lysates, suggesting that
      these proteins may associate in vivo. A previously uncharacterized Caenorhabditis
      elegans gene could encode a protein (96 kDa) possessing two Ran-binding domains.
      This open reading frame also contains similarities to nucleoporins, suggesting a
      functional link between Ran and nuclear pore complexes.

PMID- 7724563
TI  - Evolution of the chalcone synthase gene family in the genus Ipomoea.
AB  - The evolution of the chalcone synthase [CHS; malonyl-CoA:4-coumaroyl-CoA
      malonyltransferase (cyclizing), EC 2.3.1.74] multigene family in the genus
      Ipomoea is explored. Thirteen CHS genes from seven Ipomoea species (family
      Convolvulaceae) were sequenced--three from genomic clones and the remainder from
      PCR amplification with primers designed from the 5' flanking region and the end
      of the 3' coding region of Ipomoea purpurea Roth. Analysis of the data indicates
      a duplication of CHS that predates the divergence of the Ipomoea species in this
      study. The Ipomoea CHS genes are among the most rapidly evolving of the CHS genes
      sequenced to date. The CHS genes in this study are most closely related to the
      Petunia CHS-B gene, which is also rapidly evolving and highly divergent from the
      rest of the Petunia CHS sequences.

PMID- 7724564
TI  - The sulfur controller-2 negative regulatory gene of Neurospora crassa encodes a
      protein with beta-transducin repeats.
AB  - The sulfur regulatory system of Neurospora crassa is composed of a set of
      structural genes involved in sulfur catabolism controlled by a genetically
      defined set of trans-acting regulatory genes. These sulfur regulatory genes
      include cys-3+, which encodes a basic region-leucine zipper transcriptional
      activator, and the negative regulatory gene scon-2+. We report here that the scon
      2+ gene encodes a polypeptide of 650 amino acids belonging to the expanding beta
      transducin family of eukaryotic regulatory proteins. Specifically, SCON2 protein
      contains six repeated G beta-homologous domains spanning the C-terminal half of
      the protein. SCON2 represents the initial filamentous fungal protein identified
      in the beta-transducin group. Additionally, SCON2 exhibits a specific amino
      terminal domain that potentially defines another subfamily of beta-transducin
      homologs. Expression of the scon-2+ gene has been examined using RNA
      hybridization and gel mobility-shift analysis. The dependence of scon-2+
      expression on CYS3 function and the binding of CYS3 to the scon-2+ promoter
      indicate the presence of an important control loop within the N. crassa sulfur
      regulatory circuit involving CYS3 activation of scon-2+ expression. On the basis
      of the presence of beta-transducin repeats, the crucial role of SCON2 in the
      signal-response pathway triggered by sulfur limitation may be mediated by protein
      protein interactions.

PMID- 7724565
TI  - Suppression and promotion of tumor growth by monoclonal antibodies to ErbB-2
      differentially correlate with cellular uptake.
AB  - Amplification and overexpression of the erbB-2/neu protooncogene are frequently
      associated with aggressive clinical course of certain human adenocarcinomas, and
      therefore the encoded surface glycoprotein is considered a candidate target for
      immunotherapy. We previously generated a series of anti-ErbB-2 monoclonal
      antibodies (mAbs) that either accelerate or inhibit the tumorigenic growth of
      erbB-2-transformed murine fibroblasts. The present study extended this
      observation to a human tumor cell line grown as xenografts in athymic mice and
      addressed the biochemical differences between the two classes of mAbs. We show
      that the inhibitory effect is dominant in an antibody mixture, and it depends on
      antibody bivalency. By using radiolabeled mAbs we found that all of three tumor
      inhibitory mAbs became rapidly inaccessible to acid treatment when incubated with
      tumor cells. However, a tumor-stimulatory mAb remained accessible to
      extracellular treatments, indicating that it did not undergo endocytosis. In
      addition, intracellular fragments of the inhibitory mAbs, but not of the
      stimulatory mAb, were observed. Electron microscopy of colloidal gold-antibody
      conjugates confirmed the absence of endocytosis of the stimulatory mAb but
      detected endocytic vesicles containing an inhibitory mAb. We conclude that
      acceleration of cell growth by ErbB-2 correlates with cell surface localization,
      whereas inhibition of tumor growth is associated with an intrinsic ability of
      anti-ErbB-2 mAbs to induce endocytosis. These conclusions are relevant to the
      selection of optimal mAbs for immunotherapy and may have implications for the
      mechanism of cellular transformation by an overexpressed erbB-2 gene.

PMID- 7724566
TI  - Immunogenicity of transgenic plant-derived hepatitis B surface antigen.
AB  - The focus of the Children's Vaccine Initiative is to encourage the discovery of
      technology that will make vaccines more readily available to developing
      countries. Our strategy has been to genetically engineer plants so that they can
      be used as inexpensive alternatives to fermentation systems for production of
      subunit antigens. In this paper we report on the immunological response elicited
      in vivo by using recombinant hepatitis B surface antigen (rHBsAg) purified from
      transgenic tobacco leaves. The anti-hepatitis B response to the tobacco-derived
      rHBsAg was qualitatively similar to that obtained by immunizing mice with yeast
      derived rHBsAg (commercial vaccine). Additionally, T cells obtained from mice
      primed with the tobacco-derived rHBsAg could be stimulated in vitro by the
      tobacco-derived rHBsAg, yeast-derived rHBsAg, and by a synthetic peptide that
      represents part of the a determinant located in the S region (139-147) of HBsAg.
      Further support for the integrity of the T-cell epitope of the tobacco-derived
      rHBsAg was obtained by testing the ability of the primed T cells to proliferate
      in vitro after stimulation with a monoclonal anti-idiotype and an anti-idiotype
      derived peptide, both of which mimic the group-specific a determinant of HBsAg.
      In total, we have conclusively demonstrated that both B- and T-cell epitopes of
      HBsAg are preserved when the antigen is expressed in a transgenic plant.

PMID- 7724567
TI  - Habituation of an invertebrate escape reflex due to modulation by higher centers
      rather than local events.
AB  - Learning is widely thought to result from altered potency of synapses within the
      neural pathways that mediate the learned behavior. Support for this belief, which
      pervades current physiological and computational thinking, comes especially from
      the analysis of cases of simple learning in invertebrates. Here, evidence is
      presented that in one such case, habituation of crayfish escape, the learning is
      more due to onset of tonic descending inhibition than to the intrinsic depression
      of circuit synapses to which it was previously attributed. Thus, the altered
      performance seems to depend at least as much on events in higher centers as on
      local plasticity.

PMID- 7724568
TI  - Refinement of odor molecule tuning by dendrodendritic synaptic inhibition in the
      olfactory bulb.
AB  - Mitral/tufted cells (M/T cells) and granule cells form reciprocal dendrodendritic
      synapses in the main olfactory bulb; the granule cell is excited by glutamate
      from the M/T cell and in turn inhibits M/T cells by gamma-aminobutyrate. The
      trans-synaptically excited granule cell is thought to induce lateral inhibition
      in neighboring M/T cells and to refine olfactory information. It remains,
      however, elusive how significantly and specifically this synaptic regulation
      contributes to the discrimination of different olfactory stimuli. This
      investigation concerns the mechanism of olfactory discrimination by single unit
      recordings of responses to a series of normal aliphatic aldehydes from individual
      rabbit M/T cells. This analysis revealed that inhibitory responses are evoked in
      a M/T cell by a defined subset of odor molecules with structures closely related
      to the excitatory odor molecules. Furthermore, blockade of the reciprocal
      synaptic transmission by the glutamate receptor antagonist or the gamma
      aminobutyrate receptor antagonist markedly suppressed the odor-evoked inhibition,
      indicating that the inhibitory responses are evoked by lateral inhibition via the
      reciprocal synaptic transmission. The synaptic regulation in the olfactory bulb
      thus greatly enhances the tuning specificity of odor responses and would
      contribute to discrimination of olfactory information.

PMID- 7724570
TI  - Abnormal junctions between surface membrane and sarcoplasmic reticulum in
      skeletal muscle with a mutation targeted to the ryanodine receptor.
AB  - Junctions that mediate excitation-contraction (e-c) coupling are formed between
      the sarcoplasmic reticulum (SR) and either the surface membrane or the transverse
      (T) tubules in normal skeletal muscle. Two structural components of the
      junctions, the feet of the SR and the tetrads of T tubules, have been identified
      respectively as ryanodine receptors (RyRs, or SR calcium-release channels), and
      as groups of four dihydropyridine receptors (DHPRs, or voltage sensors of e-c
      coupling). A targeted mutation (skrrm1) of the gene for skeletal muscle RyRs in
      mice results in the absence of e-c coupling in homozygous offspring of transgenic
      parents. The mutant gene is expected to produce no functional RyRs, and we have
      named the mutant mice "dyspedic" because they lack feet--the cytoplasmic domain
      of RyRs anchored in the SR membrane. We have examined the development of
      junctions in skeletal muscle fibers from normal and dyspedic embryos.
      Surprisingly, despite the absence of RyRs, junctions are formed in dyspedic
      myotubes, but the junctional gap between the SR and T tubule is narrow,
      presumably because the feet are missing. Tetrads are also absent from these
      junctions. The results confirm the identity of RyRs and feet and a major role for
      RyRs and tetrads in e-c coupling. Since junctions form in the absence of feet and
      tetrads, coupling of SR to surface membrane and T tubules appears to be mediated
      by additional proteins, distinct from either RyRs or DHPRs.

PMID- 7724571
TI  - Development of a K(+)-channel probe and its use for identification of an
      intracellular plant membrane K+ channel.
AB  - Polyclonal antibodies were generated against a 9-amino acid, synthetic peptide
      corresponding to the selectivity filter in the pore region of K(+)-channel
      proteins. The sequence of amino acids in the ion-conducting pore region of K+
      channels is the only highly conserved region of members of this protein family.
      The objectives of the present work were (i) to determine whether the anti-channel
      pore peptide antibody was immunoreactive with known K(+)-channel proteins and
      (ii) to demonstrate the usefulness of the antibody by employing it to identify a
      newly discovered K(+)-channel protein. Anti-channel pore peptide was
      immunoreactive with various K(+)-channel subtypes native to a number of different
      species. Immunoblot analysis demonstrated affinity of the antibody for the drk1,
      maxi-K, and KAT1 K(+)-channel proteins. Studies also suggested that the anti
      channel pore peptide antibody did not immunoreact with membrane proteins other
      than K+ channels. The anti-channel pore peptide antibody was used to establish
      the identity of a 62-kDa chloroplast inner envelope polypeptide as a putative
      component of a K(+)-channel protein. It was concluded that an antibody generated
      against the conserved pore region/selectivity filter of K+ channels has broad but
      selective affinity for this class of proteins. This K(+)-channel probe may be a
      useful tool for identification of K(+)-channel proteins in native membranes.

PMID- 7724569
TI  - Mast cells express a peripheral cannabinoid receptor with differential
      sensitivity to anandamide and palmitoylethanolamide.
AB  - Mast cells are multifunctional bone marrow-derived cells found in mucosal and
      connective tissues and in the nervous system, where they play important roles in
      tissue inflammation and in neuroimmune interactions. Very little is known about
      endogenous molecules and mechanisms capable of modulating mast cell activation.
      Palmitoylethanolamide, found in peripheral tissues, has been proposed to behave
      as a local autacoid capable of downregulating mast cell activation and
      inflammation. A cognate N-acylamide, anandamide, the ethanolamide of arachidonic
      acid, occurs in brain and is a candidate endogenous agonist for the central
      cannabinoid receptor (CB1). As a second cannabinoid receptor (CB2) has been found
      in peripheral tissues, the possible presence of CB2 receptors on mast cells and
      their interaction with N-acylamides was investigated. Here we report that mast
      cells express both the gene and a functional CB2 receptor protein with negative
      regulatory effects on mast cell activation. Although both palmitoylethanolamide
      and anandamide bind to the CB2 receptor, only the former downmodulates mast cell
      activation in vitro. Further, the functional effect of palmitoylethanolamide, as
      well as that of the active cannabinoids, was efficiently antagonized by
      anandamide. The results suggest that (i) peripheral cannabinoid CB2 receptors
      control, upon agonist binding, mast cell activation and therefore inflammation;
      (ii) palmitoylethanolamide, unlike anandamide, behaves as an endogenous agonist
      for the CB2 receptor on mast cells; (iii) modulatory activities on mast cells
      exerted by the naturally occurring molecule strengthen a proposed autacoid local
      inflammation antagonism (ALIA) mechanism; and (iv) palmitoylethanolamide and its
      derivatives may provide antiinflammatory therapeutic strategies specifically
      targeted to mast cells ("ALIAmides").

PMID- 7724572
TI  - Transmembrane signaling characterized in bacterial chemoreceptors by using
      sulfhydryl cross-linking in vivo.
AB  - Transmembrane signaling by bacterial chemoreceptors is thought to involve
      conformational changes within a stable homodimer. We investigated the functional
      consequences of constraining movement between pairs of helices in the four-helix
      structure of the transmembrane domain of chemoreceptor Trg. Using a family of
      cysteine-containing receptors, we identified oxidation treatments for intact
      cells that catalyzed essentially complete sulfhydryl cross-linking at selected
      positions and yet left flagellar and sensory functions largely unperturbed.
      Constraining movement by cross-links between subunits had little effect on tactic
      response, but constraining movement between transmembrane segments of the monomer
      drastically reduced function. We deduce that transmembrane signaling requires
      substantial movement between transmembrane helices of a monomer but not between
      interacting helices across the interface between subunits.

PMID- 7724573
TI  - The alpha and gamma 1 isoforms of protein phosphatase 1 are highly and
      specifically concentrated in dendritic spines.
AB  - Protein phosphatase 1 (PP1) is a highly conserved enzyme that has been implicated
      in diverse biological processes in the brain as well as in nonneuronal tissues.
      The present study used light and electron microscopic immunocytochemistry to
      characterize the distribution of two PP1 isoforms, PP1 alpha and PP1 gamma 1, in
      the rat neostriatum. Both isoforms are heterogeneously distributed in brain with
      the highest immunoreactivity being found in the neostriatum and hippocampal
      formation. Further, both isoforms are highly and specifically concentrated in
      dendritic spines. Weak immunoreactivity is present in dendrites, axons, and some
      axon terminals. Immunoreactivity for PP1 alpha is also present in the perikaryal
      cytoplasm and nuclei of most medium- and large-sized neostriatal neurons. The
      specific localization of PP1 in dendritic spines is consistent with a central
      role for this enzyme in signal transduction. The data support the concept that,
      in the course of evolution, spines developed as specialized signal transduction
      organelles enabling neurons to integrate diverse inputs from multiple afferent
      nerve terminals.

PMID- 7724575
TI  - Decrements in auditory responses to a repeated conspecific song are long-lasting
      and require two periods of protein synthesis in the songbird forebrain.
AB  - Earlier work showed that playbacks of conspecific song induce expression of the
      immediate early gene ZENK in the caudo-medial neostriatum (NCM) of awake male
      zebra finches and that this response disappears with repeated presentations of
      the same stimulus. In the present study, we investigated whether repetitions of a
      song stimulus also elicited a decrement in the electrophysiological responses in
      the NCM neurons of these birds. Multiunit auditory responses in NCM were
      initially vigorous, but their amplitude decreased (habituated) rapidly to
      repeated stimulation, declining to about 40% of the initial response during the
      first 50 iterations. A similar time course of change was seen at the single unit
      level. This habituation occurred specifically for each song presented but did not
      occur when pure tones were used as a stimulus. Habituation to conspecific, but
      not heterospecific, song was retained for 20 h or longer. Injections of
      inhibitors of protein or RNA synthesis at the recording site did not affect the
      initial habituation to a novel stimulus, but these drugs blocked the long-term
      habituation when injected at 0.5-3 h and at 5.5-7 h after the first exposure to
      the stimulus. Thus, at least two waves of gene induction appear to be necessary
      for long-lasting habituation to a particular song.

PMID- 7724576
TI  - Cytokine-mediated survival from lethal herpes simplex virus infection: role of
      programmed neuronal death.
AB  - The mechanisms responsible for cytokine-mediated antiviral effects are not fully
      understood. We approached this problem by studying the outcome of intraocular
      herpes simplex (HSV) infection in transgenic mice that express interferon gamma
      in the photoreceptor cells of the retina. These transgenic mice showed selective
      survival from lethal HSV-2 infection manifested in both eyes, the optic nerve,
      and the brain. Although transgenic mice developed greater inflammatory responses
      to the virus in the eyes, inflammation and viral titers in their brains were
      equivalent to nontransgenic mice. However, survival of transgenic mice correlated
      with markedly lower numbers of central neurons undergoing apoptosis. The
      protooncogene Bcl2 was found to be induced in the HSV-2-infected brains of
      transgenic mice, allowing us to speculate on its role in fostering neuronal
      survival in this model. These observations imply a complex interaction between
      cytokine, virus, and host cellular factors. Our results suggest a cytokine
      regulated salvage pathway that allows for survival of infected neurons.

PMID- 7724574
TI  - Identification of two flavivirus-like genomes in the GB hepatitis agent.
AB  - A subtractive PCR methodology known as representational difference analysis was
      used to clone specific nucleotide sequences present in the infectious plasma from
      a tamarin infected with the GB hepatitis agent. Eleven unique clones were
      identified, seven of which were examined extensively. All seven clones appeared
      to be derived from sequences exogenous to the genomes of humans, tamarins,
      Saccharomyces cerevisiae, and Escherichia coli. In addition, sequences from these
      clones were not detected in plasma or liver tissue of tamarins prior to their
      inoculation with the GB agent. These sequences were detected by reverse
      transcription-PCR in acute-phase plasma of tamarins inoculated with the GB agent.
      Probes derived from two of the seven clones detected an RNA species of > or = 8.3
      kb in the liver of a GB-agent-infected tamarin by Northern blot hybridization.
      Sequence analysis indicated that five of the seven clones encode polypeptides
      that possess limited amino acid identity with the nonstructural proteins of
      hepatitis C virus. Extension of the sequences found in the seven clones revealed
      that plasma from an infected tamarin contained two RNA molecules > 9 kb long.
      Limited sequence identity with various isolates of hepatitis C virus and the
      relative positions of putative RNA helicases and RNA-dependent RNA polymerases in
      the predicted protein products of these molecules suggested that the GB agent
      contains two unique flavivirus-like genomes.

PMID- 7724577
TI  - Ethanol inhibits luteinizing hormone-releasing hormone (LHRH) secretion by
      blocking the response of LHRH neuronal terminals to nitric oxide.
AB  - It has previously been shown that alcohol can suppress reproduction in humans,
      monkeys, and small rodents by inhibiting release of luteinizing hormone (LH). The
      principal action is via suppression of the release of LH-releasing hormone (LHRH)
      both in vivo and in vitro. The present experiments were designed to determine the
      mechanism by which alcohol inhibits LHRH release. Previous research has indicated
      that the release of LHRH is controlled by nitric oxide (NO). The proposed pathway
      is via norepinephrine-induced release of NO from NOergic neurons, which then
      activates LHRH release. In the present experiments, we further evaluated the
      details of this mechanism in male rats by incubating medial basal hypothalamic
      (MBH) explants in vitro and examining the release of NO, prostaglandin E2 (PGE2),
      conversion of arachidonic acid to prostanoids, and production of cGMP. The
      results have provided further support for our theory of LHRH control.
      Norepinephrine increased the release of NO as measured by conversion of
      [14C]arginine to [14C]citrulline, and this increase was blocked by the alpha 1
      receptor blocker prazosin. Furthermore, the release of LHRH induced by
      nitroprusside (NP), a donor of NO, is related to the activation of soluble
      guanylate cyclase by NO since NP increased cGMP release from MBHs and cGMP also
      released LHRH. Ethanol had no effect on the production of NO by MBH explants or
      the increased release of NO induced by norepinephrine. Therefore, it does not act
      at that step in the pathway. Ethanol also failed to affect the increase in cGMP
      induced by NP. On the other hand, as might be expected from previous experiments
      indicating that LHRH release was brought about by PGE2, NP increased the
      conversion of [14C]arachidonic acid to its metabolites, particularly PGE2.
      Ethanol completely blocked the release of LHRH induced by NP and the increase in
      PGE2 induced by NP. Therefore, the results support the theory that norepinephrine
      acts to stimulate NO release from NOergic neurons. This NO diffuses to the LHRH
      terminals where it activates guanylate cyclase, leading to an increase in cGMP.
      At the same time, it also activates cyclooxygenase. The increase in cGMP
      increases intracellular free calcium, activating phospholipase A2 to provide
      arachidonic acid, the substrate for conversion by the activated cyclooxygenase to
      PGE2, which then activates the release of LHRH. Since alcohol inhibits the
      conversion of labeled arachidonic acid to PGE2, it must act either directly to
      inhibit cyclooxygenase or perhaps it may act by blocking the increase in
      intracellular free calcium induced by cGMP, which is crucial for activation of of
      both phospholipase A2 and cyclooxygenase.

PMID- 7724578
TI  - Nitric oxide inhibits hypothalamic luteinizing hormone-releasing hormone release
      by releasing gamma-aminobutyric acid.
AB  - Nitric oxide synthase (NOS)-containing neurons, termed NOergic neurons, occur in
      various regions of the hypothalamus, including the median eminence-arcuate
      region, which plays an important role in controlling the release of luteinzing
      hormone-releasing hormone (LHRH). We examined the effect of NO on release of
      gamma-aminobutyric acid (GABA) from medial basal hypothalamic (MBH) explants
      incubated in vitro. Sodium nitroprusside (NP) (300 microM), a spontaneous
      releaser of NO, doubled the release of GABA. This release was significantly
      reduced by incubation of the tissue with hemoglobin, a scavenger of NO, whereas
      hemoglobin alone had no effect on the basal release of GABA. Elevation of the
      potassium concentration (40 mM) in the medium increased GABA release 15-fold;
      this release was further augmented by NP. Hemoglobin blocked the increase in GABA
      release induced by NP but had no effect on potassium-induced release, suggesting
      that the latter is not related to NO. As in the case of hemoglobin, NG-monomethyl
      L-arginine (NMMA), a competitive inhibitor of NOS, had no effect on basal release
      of GABA, which indicates again that NO is not significant to basal GABA release.
      However, NMMA markedly inhibited the release of GABA induced by high potassium,
      which indicates that NO plays a role in potassium-induced release of GABA. In
      conditions in which the release of GABA was substantially augmented, there was a
      reduction in GABA tissue stores as well, suggesting that synthesis of GABA in
      these conditions did not keep up with release of the amine. Although NO released
      GABA, there was no effect of the released GABA on NO production, for incubation
      of MBH explants with GABA had no effect on NO release as measured by
      [14C]citrulline production. To determine whether GABA had any effect on the
      release of LHRH from these MBH explants, GABA was incubated with the tissue and
      the effect on LHRH release was determined. GABA (10(-5) or 10(-6) M) induced a
      70% decrease in the release of LHRH, indicating that in the male rat GABA
      inhibits the release of this hypothalamic peptide. This inhibition in LHRH
      release induced by GABA was blocked by NMMA (300 microM), which indicates that
      GABA converts the stimulatory effect of NO on LHRH release into an inhibitory
      one, presumably via GABA receptors, which activate chloride channels that
      hyperpolarize the cell. Previous results have indicated that norepinephrine
      stimulates release of NO from the NOergic neurons, which then stimulates the
      release of LHRH. The current results indicate that the NO released also induces
      release of GABA, which then inhibits further LHRH release. Thus, in vivo the
      norepinephrinergic-driven pulses of LHRH release may be terminated by GABA
      released from GABAergic neurons via NO.

PMID- 7724579
TI  - Mos overexpression in Swiss 3T3 cells induces meiotic-like alterations of the
      mitotic spindle.
AB  - High levels of mos protooncogene product are expressed during oocyte meiotic
      maturation and Mos has been implicated in formation of the spindle and spindle
      pole. Here, we show that in Swiss 3T3 cells with 4N DNA content, high levels of
      Mos lead to the production of binucleated cells. The Swiss 3T3 cells in mitosis,
      before binucleation occurs, are anastral and the spindle poles are juxtaposed to
      the cell membrane. These phenotypes may be related to the meiotic process of
      attachment of the spindle pole to the oocyte membrane during polar body
      formation. The production of binucleated somatic cells could result from
      attachment of the altered mitotic spindle pole to the cell membrane that
      interferes with cytokinesis but not karyokinesis. This can explain at least one
      form of genetic instability that leads to altered DNA content in tumor cells.

PMID- 7724580
TI  - Prostate cancer in a transgenic mouse.
AB  - Progress toward understanding the biology of prostate cancer has been slow due to
      the few animal research models available to study the spectrum of this uniquely
      human disease. To develop an animal model for prostate cancer, several lines of
      transgenic mice were generated by using the prostate-specific rat probasin
      promoter to derive expression of the simian virus 40 large tumor antigen-coding
      region. Mice expressing high levels of the transgene display progressive forms of
      prostatic disease that histologically resemble human prostate cancer, ranging
      from mild intraepithelial hyperplasia to large multinodular malignant neoplasia.
      Prostate tumors have been detected specifically in the prostate as early as 10
      weeks of age. Immunohistochemical analysis of tumor tissue has demonstrated that
      dorsolateral prostate-specific secretory proteins were confined to well
      differentiated ductal epithelial cells adjacent to, or within, the poorly
      differentiated tumor mass. Prostate tumors in the mice also display elevated
      levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor
      expression, as observed in advanced human prostate cancer. The establishment of
      breeding lines of transgenic mice that reproducibly develop prostate cancer
      provides an animal model system to study the molecular basis of transformation of
      normal prostatic cells and the factors influencing the progression to metastatic
      prostate cancer.

PMID- 7724581
TI  - Heterogeneity in molecular recognition by restriction endonucleases: osmotic and
      hydrostatic pressure effects on BamHI, Pvu II, and EcoRV specificity.
AB  - The cleavage specificity of the Pvu II and BamHI restriction endonucleases is
      found to be dramatically reduced at elevated osmotic pressure. Relaxation in
      specificity of these otherwise highly accurate and specific enzymes, previously
      termed "star activity," is uniquely correlated with osmotic pressure between 0
      and 100 atmospheres. No other colligative solvent property exhibits a uniform
      correlation with star activity for all of the compounds tested. Application of
      hydrostatic pressure counteracts the effects of osmotic pressure and restores the
      natural selectivity of the enzymes for their canonical recognition sequences.
      These results indicate that water solvation plays an important role in the site
      specific recognition of DNA by many restriction enzymes. Osmotic pressure did not
      induce an analogous effect on the specificity of the EcoRV endonuclease, implying
      that selective hydration effects do not participate in DNA recognition in this
      system. Hydrostatic pressure was found to have little effect on the star activity
      induced by changes in ionic strength, pH, or divalent cation, suggesting that
      distinct mechanisms may exist for these observed alterations in specificity.
      Recent evidence has indicated that BamHI and EcoRI share similar structural
      motifs, while Pvu II and EcoRV belong to a different structural family.
      Evidently, the use of hydration water to assist in site-specific recognition is a
      motif neither limited to nor defined by structural families.

PMID- 7724582
TI  - Retro and retroenantio analogs of cecropin-melittin hybrids.
AB  - Hybrid analogs of cecropin A (CA) and melittin (M), which are potent
      antibacterial peptides, have been synthesized. To understand the structural
      requirements for this antibacterial activity, we have also synthesized the
      enantio, retro, and retroenantio isomers of two of the hybrids and their N
      terminally acetylated derivatives. All analogs of CA(1-13)M(1-13)-NH2 were as
      active as the parent peptide against five test bacterial strains, but one
      bacterial strain was resistant to the retro and retroenantio derivatives.
      Similarly, all analogs of CA(1-7)M(2-9)-NH2 were active against four strains,
      while two strains were resistant to the retro and retroenantio analogs containing
      free NH3+ end groups, but acetylation restored activity against one of them. From
      these data it was concluded that chirality of the peptide was not a critical
      feature, and full activity could be achieved with peptides containing either all
      L- or all D-amino acids in their respective right-handed or left-handed helical
      conformations. For most of the bacterial strains, the sequence of these peptides
      or the direction of the peptide bonds could be critical but not both at the same
      time. For some strains, both needed to be conserved.

PMID- 7724583
TI  - Phosphorylation of ubiquitin-activating enzyme in cultured cells.
AB  - Ubiquitin-activating enzyme, E1, is the first enzyme in the pathway leading to
      formation of ubiquitin-protein conjugates. E1 exists as two isoforms in human
      cells which are separable by electrophoresis. These isoforms migrate with
      apparent molecular sizes of 110 kDa and 117 kDa in SDS/polyacrylamide gels.
      Immunoprecipitation of E1 from lysates of HeLa cells metabolically labeled with
      [32P]phosphate indicated the presence of a phosphorylated form of E1 which
      migrates at 117 kDa. Phospho amino acid analysis identified serine as the
      phosphorylated residue in E1. Phosphorylated E1 was also detected in normal and
      transformed cells from another human cell line. Phosphatase-catalyzed
      dephosphorylation of E1 in vitro did not eliminate the 117-kDa E1 isoform
      detected by Coomassie staining after SDS/polyacrylamide gel electrophoresis,
      thereby demonstrating that phosphorylation is not the sole structural feature
      differentiating the isoforms of E1. These observations suggest new hypotheses
      concerning mechanisms of metabolic regulation of the ubiquitin conjugation
      pathway.

PMID- 7724584
TI  - Molecular cloning and characterization of a cDNA encoding monoclonal nonspecific
      suppressor factor.
AB  - The monoclonal nonspecific suppressor factor (MNSF) is a lymphokine product of a
      murine T-cell hybridoma that inhibits the generation of lipopolysaccharide
      induced immunoglobulin-secreting cells in an antigen-nonspecific manner. A cDNA
      clone encoding MNSF beta (an isoform of MNSF) was isolated and expressed in
      bacteria. The sequence obtained is virtually identical to the Fau protein, a
      product of the ubiquitously expressed fau gene with unknown function. Northern
      blot analysis demonstrated a single, 0.6-kb transcript. Specific polyclonal
      antibodies against synthetic peptides corresponding to the deduced amino acid
      sequences were elicited in rabbits. Immunoprecipitation experiments with these
      antibodies showed that MNSF beta is released extracellularly in an aggregate
      form, albeit it lacks a signal peptide sequence. The anti-MNSF beta affinity
      eluate from the MNSF-producing murine hybridoma (E17) and concanavalin A
      activated splenocyte culture supernatants inhibited the immunoglobulin production
      by lipopolysaccharide-activated splenocytes. Recombinant MNSF beta also showed a
      similar biologic activity. Thus, ubiquitin-like protein(s) may be involved in the
      regulation of the immune responses.

PMID- 7724586
TI  - Two auxin-responsive domains interact positively to induce expression of the
      early indoleacetic acid-inducible gene PS-IAA4/5.
AB  - The plant growth hormone indole-3-acetic acid (IAA) transcriptionally activates
      expression of several genes in plants. We have previously identified a 164-bp
      promoter region (-318 to -154) in the PS-IAA4/5 gene that confers IAA
      inducibility. Linker-scanning mutagenesis across the region has identified two
      positive domains: domain A (48 bp; -203 to -156) and domain B (44 bp; -299 to 
      256), responsible for transcriptional activation of PS-IAA4/5 by IAA. Domain A
      contains the highly conserved sequence 5'-TGTCCCAT-3' found among various IAA
      inducible genes and behaves as the major auxin-responsive element. Domain B
      functions as an enhancer element which may also contain a less efficient auxin
      responsive element. The two domains act cooperatively to stimulate transcription;
      however, tetramerization of domain A or B compensates for the loss of A or B
      function. The two domains can also mediate IAA-induced transcription from the
      heterologous cauliflower mosaic virus 35S promoter (-73 to +1). In vivo
      competition experiments with icosamers of domain A or B show that the domains
      interact specifically and with different affinities to low abundance, positive
      transcription factor(s). A model for transcriptional activation of PS-IAA4/5 by
      IAA is discussed.

PMID- 7724585
TI  - DNA-strand exchange promoted by RecA protein in the absence of ATP: implications
      for the mechanism of energy transduction in protein-promoted nucleic acid
      transactions.
AB  - DNA-strand exchange promoted by Escherichia coli RecA protein normally requires
      the presence of ATP and is accompanied by ATP hydrolysis, thereby implying a need
      for ATP hydrolysis. Previously, ATP hydrolysis was shown not to be required; here
      we demonstrate furthermore that a nucleoside triphosphate cofactor is not
      required for DNA-strand exchange. A gratuitous allosteric effector consisting of
      the noncovalent complex of ADP and aluminum fluoride, ADP.AIF4-, can both induce
      the high-affinity DNA-binding state of RecA protein and support the homologous
      pairing and exchange of up to 800-900 bp of DNA. These results demonstrate that
      induction of the functionally active, high-affinity DNA-binding state of RecA
      protein is needed for RecA protein-promoted DNA-strand exchange and that there is
      no requirement for a high-energy nucleotide cofactor for the exchange of DNA
      strands. Consequently, the free energy needed to activate the DNA substrates for
      DNA-strand exchange is not derived from ATP hydrolysis. Instead, the needed free
      energy is derived from ligand binding and is transduced to the DNA via the
      associated ligand-induced structural transitions of the RecA protein-DNA complex;
      ATP hydrolysis simply destroys the effector ligand. This concept has general
      applicability to the mechanism of energy transduction by proteins.

PMID- 7724587
TI  - Cell cycle-related shifts in subcellular localization of BCR: association with
      mitotic chromosomes and with heterochromatin.
AB  - The disruption of the BCR gene and its juxtaposition to and consequent activation
      of the ABL gene has been implicated as the critical molecular defect in
      Philadelphia chromosome-positive leukemias. The normal BCR protein is a
      multifunctional molecule with domains that suggest its participation in
      phosphokinase and GTP-binding pathways. Taken together with its localization to
      the cytoplasm of uncycled cells, it is therefore presumed to be involved in
      cytoplasmic signaling. By performing a double aphidicolin block for cell cycle
      synchronization, we currently demonstrate that the subcellular localization of
      BCR shifts from being largely cytoplasmic in interphase cells to being
      predominantly perichromosomal in mitosis. Furthermore, with the use of immunogold
      labeling and electron microscopy, association of BCR with DNA, in particular
      heterochromatin, can be demonstrated even in quiescent cells. Results were
      similar in cell lines of lymphoid or myeloid origin. These observations suggest a
      role for BCR in the phosphokinase interactions linked to condensed chromatin, a
      network previously implicated in cell cycle regulation.

PMID- 7724588
TI  - Promotion of purine nucleotide binding to thymidylate synthase by a potent folate
      analogue inhibitor, 1843U89.
AB  - A folate analogue, 1843U89 (U89), with potential as a chemotherapeutic agent due
      to its potent and specific inhibition of thymidylate synthase (TS; EC 2.1.1.45),
      greatly enhances not only the binding of 5-fluoro-2'-deoxyuridine 5'
      monophosphate (FdUMP) and dUMP to Escherichia coli TS but also that of dGMP, GMP,
      dIMP, and IMP. Guanine nucleotide binding was first detected by CD analysis,
      which revealed a unique spectrum for the TS-dGMP-U89 ternary complex. The
      quantitative binding of dGMP relative to GMP, FdUMP, and dUMP was determined in
      the presence and absence of U89 by ultrafiltration analysis, which revealed that
      although the binding of GMP and dGMP could not be detected in the absence of U89
      both were bound in its presence. The Kd for dGMP was about the same as that for
      dUMP and FdUMP, with binding of the latter two nucleotides being increased by two
      orders of magnitude by U89. An explanation for the binding of dGMP was provided
      by x-ray diffraction studies that revealed an extensive stacking interaction
      between the guanine of dGMP and the benzoquinazoline ring of U89 and hydrogen
      bonds similar to those involved in dUMP binding. In addition, binding energy was
      provided through a water molecule that formed hydrogen bonds to both N7 of dGMP
      and the hydroxyl of Tyr-94. Accommodation of the larger dGMP molecule was
      accomplished through a distortion of the active site and a shift of the
      deoxyribose moiety to a new position. These rearrangements also enabled the
      binding of GMP to occur by creating a pocket for the ribose 2' hydroxyl group,
      overcoming the normal TS discrimination against nucleotides containing the 2'
      hydroxyl.

PMID- 7724589
TI  - Synthesis of "Nod"-like chitin oligosaccharides by the Xenopus developmental
      protein DG42.
AB  - The Xenopus DG42 gene is expressed only between the late midblastula and
      neurulation stages of embryonic development. Recent database searches show that
      DG42 has striking sequence similarity to the Rhizobium NodC protein. NodC
      catalyzes the synthesis of chitin oligosaccharides which subsequently are
      transformed into bacterium-plant root signaling molecules. We find that the DG42
      protein made in an in vitro coupled transcription-translation system catalyzes
      the synthesis of an array of chitin oligosaccharides. The result suggests the
      intriguing possibility that a bacterium-plant type of "Nod" signaling system may
      operate during early stages of vertebrate embryonic development and raises issues
      about the use of chitin synthase inhibitors as fungal-specific drugs.

PMID- 7724590
TI  - Fluctuation analysis of rotational speeds of the bacterial flagellar motor.
AB  - We measured the dependence of the variance in the rotation rate of tethered cells
      of Escherichia coli on the mean rotation rate over a regime in which the motor
      generates constant torque. This dependence was compared with that of broken
      motors. In either case, motor torque was augmented with externally applied
      torque. We show that, in contrast to broken motors, functioning motors in this
      regime do not freely rotationally diffuse and that the variance measurements are
      consistent with the predicted values of a stepping mechanism with exponentially
      distributed waiting times (a Poisson stepper) that steps approximately 400 times
      per revolution.

PMID- 7724591
TI  - Isolation of a differentially regulated splicing isoform of human NF-E2.
AB  - The transcription factor NF-E2 (nuclear factor erythroid 2), interacting via DNA
      motifs within regulatory regions of several hematopoietic genes, is thought to
      mediate the enhancer activity of the globin locus control regions. By screening a
      human fetal liver cDNA library with probes derived from mouse NF-E2, we have
      isolated a splicing variant of the NF-E2 gene (fNF-E2) that differs in the 5'
      untranslated region from the previously reported cDNA (aNF-E2). The fNF-E2
      isoform is transcribed from an alternative promoter located in the 3' end of the
      first intron and joined by alternative splicing to the second and third exons,
      which are shared by both RNA isoforms. Although the two forms produce the same
      protein, they are expressed in different ratios during development. fNF-E2 is
      more abundant in the fetal liver and less abundant in the adult bone marrow
      compared to the previously described form. Their distribution apparently follows
      the differential expression of fetal and adult hemoglobins.

PMID- 7724592
TI  - Degradation of sigma 32, the heat shock regulator in Escherichia coli, is
      governed by HflB.
AB  - The heat shock response in Escherichia coli is governed by the concentration of
      the highly unstable sigma factor sigma 32. The essential protein HflB (FtsH),
      known to control proteolysis of the phage lambda cII protein, also governs sigma
      32 degradation: an HflB-depleted strain accumulated sigma 32 and induced the heat
      shock response, and the half-life of sigma 32 increased by a factor up to 12 in
      mutants with reduced HflB function and decreased by a factor of 1.8 in a strain
      overexpressing HflB. The hflB gene is in the ftsJ-hflB operon, one promoter of
      which is positively regulated by heat shock and sigma 32. The lambda cIII
      protein, which stabilizes sigma 32 and lambda cII, appears to inhibit the HflB
      governed protease. The E. coli HflB protein controls the stability of two master
      regulators, lambda cII and sigma 32, responsible for the lysis-lysogeny decision
      of phage lambda and the heat shock response of the host.

PMID- 7724594
TI  - Coexpression of two functionally independent p58 inhibitory receptors in human
      natural killer cell clones results in the inability to kill all normal allogeneic
      target cells.
AB  - In the present study, we define a group of natural killer (NK) clones (group 0)
      that fails to lyse all of the normal allogeneic target cells analyzed. Their
      specificity for HLA class I molecules was suggested by their ability to lyse
      class I-negative target cells and by the fact that they could lyse resistant
      target cells in the presence of selected anti-class I monoclonal antibodies. The
      use of appropriate target cells represented by either HLA-homozygous cell lines
      or cell transfectants revealed that these clones recognized all the HLA-C
      alleles. By the use of monoclonal antibodies directed to either GL183 or EB6
      molecules, we showed that the EB6 molecules were responsible for the recognition
      of Cw4 and related alleles, while the GL183 molecules recognized Cw3 (and related
      C alleles). These data suggest that the GL183 and the EB6 molecules can function,
      in individual NK clones, as independent receptors for two different groups of HLA
      C alleles, (which include all known alleles for locus C), thus resulting in their
      inability to lyse all normal HLA-C+ target cells. Indirect immunofluorescence and
      fluorescence-activated cell sorting analysis revealed that the presently defined
      GL183+EB6+ group 0 NK clones brightly express EB6 molecules (EB6bright) while the
      GL183+EB6+ group 2 clones (unable to recognize Cw4) express an EB6dull phenotype.
      These data also imply that the density of EB6 receptors may be critical for the
      generation of an optimal negative signal upon interaction with appropriate HLA-C
      alleles.

PMID- 7724593
TI  - Regulation of blood pressure by the type 1A angiotensin II receptor gene.
AB  - The renin-angiotensin system plays a critical role in sodium and fluid
      homeostasis. Genetic or acquired alterations in the expression of components of
      this system are strongly implicated in the pathogenesis of hypertension. To
      specifically examine the physiological and genetic functions of the type 1A
      receptor for angiotensin II, we have disrupted the mouse gene encoding this
      receptor in embryonic stem cells by gene targeting. Agtr1A(-/-) mice were born in
      expected numbers, and the histomorphology of their kidneys, heart, and
      vasculature was normal. AT1 receptor-specific angiotensin II binding was not
      detected in the kidneys of homozygous Agtr1A(-/-) mutant animals, and Agtr1A(+/-)
      heterozygotes exhibited a reduction in renal AT1 receptor-specific binding to
      approximately 50% of wild-type [Agtr1A(+/+)] levels. Pressor responses to infused
      angiotensin II were virtually absent in Agtr1A(-/-) mice and were qualitatively
      altered in Agtr1A(+/-) heterozygotes. Compared with wild-type controls, systolic
      blood pressure measured by tail cuff sphygmomanometer was reduced by 12 mmHg (1
      mmHg = 133 Pa) in Agtr1A(+/-) mice and by 24 mmHg in Agtr1A(-/-) mice. Similar
      differences in blood pressure between the groups were seen when intraarterial
      pressures were measured by carotid cannulation. These studies demonstrate that
      type 1A angiotensin II receptor function is required for vascular and hemodynamic
      responses to angiotensin II and that altered expression of the Agtr1A gene has
      marked effects on blood pressures.

PMID- 7724595
TI  - Infection of cells by varicella zoster virus: inhibition of viral entry by
      mannose 6-phosphate and heparin.
AB  - Envelope glycoproteins of varicella zoster virus (VZV) contain mannose 6
      phosphate (Man6P) residues. We now report that Man6P competitively and
      selectively inhibits infection of cells in vitro by cell-free VZV; furthermore,
      dephosphorylation of VZV by exposure to alkaline phosphatase rapidly destroys
      infectivity. Cells are also protected from VZV in a concentration-dependent
      manner by heparin (ED50 = 0.23 micrograms/ml; 95% confidence limits = 0.16-0.26
      microgram/ml) but not by chondroitin sulfate. Both heparin and Man6P are
      protective only when present about the time of inoculation. Heparin but not Man6P
      interferes with the attachment of VZV to cell surfaces; moreover, VZV binds to
      heparin-affinity columns. These data are compatible with a working hypothesis,
      whereby VZV attaches to cell surfaces by binding to a heparin sulfate
      proteoglycan. This binding stabilizes VZV, making possible a low-affinity
      interaction with another Man6P-dependent receptor, which is necessary for viral
      entry.

PMID- 7724596
TI  - Constitutive activation of phototransduction by K296E opsin is not a cause of
      photoreceptor degeneration.
AB  - The missense mutation Lys-296-->Glu (K296E) in the rhodopsin gene produces an
      opsin with no chromophore binding site and therefore is not activated by light.
      Nevertheless, the mutant opsin constitutively activates transducin in vitro and
      causes photoreceptor degeneration in vivo, possibly by continuously activating
      the phototransduction cascade, analogous to constant exposure to environmental
      light. We studied the K296E mutation in eight lines of transgenic mice. Each line
      developed photoreceptor degeneration with the rate of degeneration increasing
      monotonically as the ratio of mutant:wild-type opsin mRNA increased. At no time
      in the course of degeneration was there endogenous light adaptation in the retina
      as measured by the electroretinogram. The mutant opsin was found to be invariably
      phosphorylated and stably bound to arrestin. Light-independent activation of
      transducin was demonstrated only after the removal of arrestin and
      dephosphorylation of K296E opsin. Thus, K296E opsin in vivo does not activate the
      phototransduction cascade because it is shut off by photoreceptor inactivation
      mechanisms. Our data show that the K296E mutation does not cause photoreceptor
      degeneration by continuous activation of phototransduction.

PMID- 7724597
TI  - Feedback from luminosity horizontal cells mediates depolarizing responses of
      chromaticity horizontal cells in the Xenopus retina.
AB  - It has been proposed that the depolarizing responses of chromaticity horizontal
      cells (C-HCs) to red light depend on a feedback signal from luminosity horizontal
      cells (L-HCs) to short-wavelength-sensitive cones in the retinas of lower
      vertebrates. In this regard we studied the C-HCs of the Xenopus retina. C-HCs and
      L-HCs were identified by physiological criteria and then injected with
      neurobiotin. The retina then was incubated with peanut agglutinin, which stains
      red-but not blue-sensitive cones. Electron microscopic examination revealed that
      L-HCs contact all cone classes, whereas C-HCs contact only blue-sensitive cones.
      Simultaneous recordings from C-HC/L-HC pairs established that when the L-HC was
      saturated by a steady bright red light, C-HCs alone responded to a superimposed
      blue stimulus. In response to red test flashes, the C-HC response was delayed by
      approximately 30 msec with respect to the L-HC response. Isolated HCs of both
      subtypes were examined by whole-cell patch clamp. Both responded to kainate with
      sustained inward currents and to quisqualate or alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) with desensitizing currents from a negative
      holding potential; i.e., both have AMPA-type glutamate receptors. gamma
      Aminobutyric acid or glycine opened a chloride channel in the L-HC, whereas the C
      HC was unresponsive to either inhibitory amino acid. Since glycine has been shown
      to abolish selectively the depolarizing response of the C-HC, this finding and
      other pharmacological data strongly implicate the L-HC in the underlying circuit.
      Moreover, because the C-HC does not respond to gamma-aminobutyric acid, the
      neurotransmitter of the L-HC, by elimination, a feedback synapse from L-HC to
      blue cone is the most plausible mechanism for the creation of depolarizing
      responses in C-HCs.

PMID- 7724598
TI  - Induction of the gene encoding mucosal vascular addressin cell adhesion molecule
      1 by tumor necrosis factor alpha is mediated by NF-kappa B proteins.
AB  - Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is involved in
      trafficking of lymphocytes to mucosal endothelium. Expression of MAdCAM-1 is
      induced in the murine endothelial cell line bEnd.3 by tumor necrosis factor alpha
      (TNF-alpha), interleukin 1, and bacterial lipopolysaccharide. Here we show that
      TNF-alpha enhances expression of a firefly luciferase reporter directed by the
      MAdCAM-1 promoter, confirming transcriptional regulation of MAdCAM-1. Mutational
      analysis of the promoter indicates that a DNA fragment extending from nt -132 to
      nt +6 of the gene is sufficient for TNF-alpha inducibility. Two regulatory sites
      critical for TNF-alpha induction were identified in this region. DNA-binding
      experiments demonstrate that NF-kappa B proteins from nuclear extracts of TNF
      alpha-stimulated bEnd.3 cells bind to these sites, and transfection assays with
      promoter mutants of the MAdCAM-1 gene indicate that occupancy of both sites is
      essential for promoter function. The predominant NF-kappa B binding activity
      detected with these nuclear extracts is a p65 homodimer. These findings establish
      that, as with other endothelial cell adhesion molecules, transcriptional
      induction of MAdCAM-1 by TNF-alpha requires activated NF-kappa B proteins.

PMID- 7724599
TI  - Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic
      endothelium during development.
AB  - We have recently cloned the human fms-like tyrosine kinase 4 gene FLT4, whose
      protein product is related to two vascular endothelial growth factor receptors
      FLT1 and KDR/FLK1. Here the expression of FLT4 has been analyzed by in situ
      hybridization during mouse embryogenesis and in adult human tissues. The FLT4
      mRNA signals first became detectable in the angioblasts of head mesenchyme, the
      cardinal vein, and extraembryonally in the allantois of 8.5-day postcoitus (p.c.)
      embryos. In 12.5-day p.c. embryos, the FLT4 signal decorated developing venous
      and presumptive lymphatic endothelia, but arterial endothelia were negative.
      During later stages of development, FLT4 mRNA became restricted to vascular
      plexuses devoid of red cells, representing developing lymphatic vessels. Only the
      lymphatic endothelia and some high endothelial venules expressed FLT4 mRNA in
      adult human tissues. Increased expression occurred in lymphatic sinuses in
      metastatic lymph nodes and in lymphangioma. Our results suggest that FLT4 is a
      marker for lymphatic vessels and some high endothelial venules in human adult
      tissues. They also support the theory on the venous origin of lymphatic vessels.

PMID- 7724600
TI  - A receptor guanylyl cyclase expressed specifically in olfactory sensory neurons.
AB  - We have cloned an additional member (GC-D) of the membrane receptor guanylyl
      cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] family that is
      specifically expressed in a subpopulation of olfactory sensory neurons. The
      extracellular, putative ligand-binding domain of the olfactory cyclase is similar
      in primary structure to two guanylyl cyclases expressed in the retina but
      diverges considerably from other known guanylyl cyclases. The expression of GC-D
      RNA is restricted to a small, randomly dispersed population of neurons that is
      within a single topographic zone in the olfactory neuroepithelium and resembles
      the pattern of the more diverse seven-transmembrane-domain odorant receptors.
      These observations suggest that GC-D may function directly in odor recognition or
      in modulating the sensitivity of a subpopulation of sensory neurons to specific
      odors.

PMID- 7724602
TI  - A constant radius of curvature model for the organization of DNA in toroidal
      condensates.
AB  - Toroidal DNA condensates have received considerable attention for their possible
      relationship to the packaging of DNA in viruses and in general as a model of
      ordered DNA condensation. A spool-like model has primarily been supported for DNA
      organization within toroids. However, our observations suggest that the actual
      organization may be considerably different. We present an alternate model in
      which DNA for a given toroid is organized within a series of equally sized
      contiguous loops that precess about the toroid axis. A related model for the
      toroid formation process is also presented. This kinetic model predicts a
      distribution of toroid sizes for DNA condensed from solution that is in good
      agreement with experimental data.

PMID- 7724601
TI  - Conditional transformation of a pancreatic beta-cell line derived from transgenic
      mice expressing a tetracycline-regulated oncogene.
AB  - Conditional oncogene expression in transgenic mice is of interest for studying
      the oncoprotein requirements during tumorigenesis and for deriving cell lines
      that can be induced to undergo growth arrest and enhance their differentiated
      functions. We utilized the bacterial tetracycline (Tet)-resistance operon
      regulatory system (tet) from Tn10 of Escherichia coli to control simian virus 40
      (SV40) large tumor (T) antigen (TAg) gene expression and to generate
      conditionally transformed pancreatic beta cells in transgenic mice. A fusion
      protein containing the tet repressor (tetR) and the activating domain of the
      herpes simplex virus protein VP16, which converts the repressor into a
      transcription activator, was produced in beta cells of transgenic mice under
      control of the insulin promoter. In a separate lineage of transgenic mice, the
      TAg gene was introduced under control of a tandem array of tet operator sequences
      and a minimal promoter, which by itself is not sufficient for gene expression.
      Mice from the two lineages were then crossed to generate double-transgenic mice.
      Expression of the tetR fusion protein in beta cells activated TAg transcription,
      resulting in the development of beta-cell tumors. Tumors arising in the absence
      of Tet were cultured to derive a stable beta-cell line. Cell incubation in the
      presence of Tet led to inhibition of proliferation, as shown by decreased BrdUrd
      and [3H]thymidine incorporation. The Tet derivative anhydrotetracycline showed a
      100-fold stronger inhibition compared with Tet. When administered in vivo, Tet
      efficiently inhibited beta-cell proliferation. These findings indicate that
      transformed beta cells selected for growth during a tumorigenesis process in vivo
      maintain a dependence on the continuous presence of the TAg oncoprotein for their
      proliferation. This system provides an approach for generation of beta-cell lines
      for cell therapy of diabetes as well as conditionally transformed cell lines from
      other cell types of interest.

PMID- 7724603
TI  - Quantitative analysis of senile plaques in Alzheimer disease: observation of log
      normal size distribution and molecular epidemiology of differences associated
      with apolipoprotein E genotype and trisomy 21 (Down syndrome).
AB  - The discovery that the epsilon 4 allele of the apolipoprotein E (apoE) gene is a
      putative risk factor for Alzheimer disease (AD) in the general population has
      highlighted the role of genetic influences in this extremely common and disabling
      illness. It has long been recognized that another genetic abnormality, trisomy 21
      (Down syndrome), is associated with early and severe development of AD
      neuropathological lesions. It remains a challenge, however, to understand how
      these facts relate to the pathological changes in the brains of AD patients. We
      used computerized image analysis to examine the size distribution of one of the
      characteristic neuropathological lesions in AD, deposits of A beta peptide in
      senile plaques (SPs). Surprisingly, we find that a log-normal distribution fits
      the SP size distribution quite well, motivating a porous model of SP
      morphogenesis. We then analyzed SP size distribution curves in genotypically
      defined subgroups of AD patients. The data demonstrate that both apoE epsilon
      4/AD and trisomy 21/AD lead to increased amyloid deposition, but by apparently
      different mechanisms. The size distribution curve is shifted toward larger
      plaques in trisomy 21/AD, probably reflecting increased A beta production. In
      apoE epsilon 4/AD, the size distribution is unchanged but the number of SP is
      increased compared to apoE epsilon 3, suggesting increased probability of SP
      initiation. These results demonstrate that subgroups of AD patients defined on
      the basis of molecular characteristics have quantitatively different
      neuropathological phenotypes.

PMID- 7724604
TI  - Proprotein convertases in amphioxus: predicted structure and expression of
      proteases SPC2 and SPC3.
AB  - SPC2 and SPC3 are two members of a family of subtilisin-related proteases which
      play essential roles in the processing of prohormones into their mature forms in
      the pancreatic B cell and many other neuroendocrine cells. To investigate the
      phylogenetic origins and evolutionary functions of SPC2 and SPC3 we have
      identified and cloned cDNAs encoding these enzymes from amphioxus (Branchiostoma
      californiensis), a primitive chordate. The amino acid sequence of preproSPC2
      contains 689 aa and is 71% identical to human SPC2. In contrast, amphioxus
      prproSPC3 consists of 774 aa and exhibits 55% identity to human SPC3. These
      results suggest that the primary structure of SPC2 has been more highly conserved
      during evolution than that of SPC3. To further investigate the function(s) of
      SPC2 and SPC3 in amphioxus, we have determined the regional expression of these
      genes by using a reverse transcriptase-linked polymerase chain reaction (RT-PCR)
      assay. Whole amphioxus was dissected longitudinally into four equal-length
      segments and RNA was extracted. Using RT-PCR to simultaneously amplify SPC2 and
      SPC3 DNA fragments, we found that the cranial region (section 1) expressed equal
      amounts of SPC2 and SPC3 mRNAs, whereas in the caudal region (section 4) the SPC2
      to-SPC3 ratio was 5:1. In the mid-body sections 2 and 3 the SPC2-to-SPC3 ratio
      was 1:5. By RT-PCR we also determined that amphioxus ILP, a homologue of
      mammalian insulin/insulin-like growth factor, was expressed predominately in
      section 3. These results suggest that the relative levels of SPC2 and SPC3 mRNAs
      are specifically regulated in various amphioxus tissues. Furthermore, the
      ubiquitous expression of these mRNAs in the organism indicates that they are
      involved in the processing of other precursor proteins in addition to proILP.

PMID- 7724605
TI  - A regulatory element in the promoter of the human granulocyte-macrophage colony
      stimulating factor gene that has related sequences in other T-cell-expressed
      cytokine genes.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine with a
      broad spectrum of cell-differentiating and colony-stimulating activities. It is
      expressed by several undifferentiated (bone marrow stromal cells, fibroblasts)
      and fully differentiated (T cells, macrophages, and endothelial cells) cells. Its
      expression in T cells is activation dependent. We have found a regulatory element
      in the promoter of the GM-CSF gene which contains two symmetrically nested
      inverted repeats (-192 CTTGGAAAGGTTCATTAATGAAAACCCCCAAG -161). In transfection
      assays with the human GM-CSF promoter, this element has a strong positive effect
      on the expression of a reporter gene by the human T-cell line Jurkat J6 upon
      stimulation with phorbol dibutyrate and ionomycin or anti-CD3 antibody. This
      element also acts as an enhancer when inserted into a minimal promoter vector. In
      DNA band-retardation assays this sequence produces six specific bands that
      involve one or the other of the inverted repeats. We have also shown that a DNA
      protein complex can be formed involving both repeats and probably more than one
      protein. The external inverted repeat contains a core sequence CTTGG...CCAAG,
      which is also present in the promoters of several other T-cell-expressed human
      cytokines (interleukins 4, 5, and 13). The corresponding elements in GM-CSF and
      interleukin 5 promoters compete for the same proteins in band-retardation assays.
      The palindromic elements in these genes are larger than the core sequence,
      suggesting that some of the interacting proteins may be different for different
      genes. Considering the strong positive regulatory effect and their presence in
      several T-cell-expressed cytokine genes, these elements may be involved in the
      coordinated expression of these cytokines in T-helper cells.

PMID- 7724606
TI  - Differential modulation of Th1- and Th2-related cytokine mRNA expression by a
      synthetic peptide homologous to a conserved domain within retroviral envelope
      protein.
AB  - The influence of a synthetic retroviral peptide, CKS-17, on T helper type 1 (Th1)
      or Th2-related cytokines was investigated in human blood mononuclear cells.
      Cells were stimulated with staphylococcal enterotoxin A, anti-CD3 plus anti-CD28
      monoclonal antibodies, or lipopolysaccharide to induce cytokine mRNA. mRNA was
      detected by a reverse transcription-polymerase chain reaction or Northern blot
      analysis. CKS-17 down-regulated stimulant-induced mRNA accumulation for
      interferon gamma (IFN-gamma), interleukin (IL)-2, and p40 heavy and p35 light
      chains of IL-12, a cytokine that mediates development of Th1 response. CKS-17 up
      regulated stimulant-induced mRNA accumulation of IL-10 and did not suppress Th2
      related cytokine (IL-4, IL-5, IL-6, or IL-13) mRNA expression. A reverse sequence
      of CKS-17 peptide, used as a control, showed no such action. Anti-human IL-10
      monoclonal antibody blocked ability of CKS-17 to inhibit mRNA accumulation for
      IFN-gamma but not the CKS-17 suppressive activity of IL-12 p40 heavy chain mRNA.
      Thus, CKS-17-mediated suppression of IFN-gamma mRNA expression is dependent upon
      augmentation of IL-10 production by CKS-17. This conserved component of several
      retroviral envelope proteins, CKS-17, may act as an immunomodulatory epitope
      responsible for cytokine dysregulation that leads to suppression of cellular
      immunity.

PMID- 7724607
TI  - Identification of a DNA transformation gene required for com101A+ expression and
      supertransformer phenotype in Haemophilus influenzae.
AB  - DNA sequencing, RNA mapping, and protein expression experiments revealed the
      presence of a gene, tfoX+, encoding a 24.9-kDa polypeptide, that is transcribed
      divergently from a common promoter region with the Haemophilus influenzae rec-1+
      gene. H. influenzae strains mutant for tfoX failed to bind transforming DNA and
      were transformation deficient. Primer extension experiments utilizing in vivo
      total RNA from precompetent and competent H. influenzae cells demonstrated that
      transcription of tfoX+ increased immediately upon competence induction,
      suggesting that tfoX+ is an early competence gene. Similar experiments showed
      that the expression of the late competence-specific gene, com101A+, was tfoX+
      dependent. Moreover, expression of plasmid-borne tfoX+ in H. influenzae resulted
      in constitutive competence. The addition of cyclic adenosine monophosphate (cAMP)
      to strains carrying a tfoX::lacZ operon fusion resulted in an immediate increase
      in beta-galactosidase activity that correlated with an increase in genetic
      transformability. Collectively, our results suggest that TfoX may play a key role
      in the development of genetic competence by regulating the expression of late
      competence-specific genes.

PMID- 7724608
TI  - The glucocorticoid receptor type II complex is a target of the HIV-1 vpr gene
      product.
AB  - The vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a 15-kDa
      virion-associated protein that functions as a regulator of cellular processes
      linked to the HIV life cycle. We report the interaction of a 41-kDa cytosolic
      viral protein R interacting protein 1 (Rip-1) with Vpr in vitro. Rip-1 displays a
      wide tissue distribution, including relevant targets of HIV infection. Vpr
      protein induced nuclear translocation of Rip-1, as did glucocorticoid receptor
      (GR)-II-stimulating steroids. Importantly, Vpr and Rip-1 coimmunoprecipitated
      with the human GR as part of an activated receptor complex. Vpr complementation
      of a vpr mutant virus was also mimicked by GR-II-stimulating steroids. Vpr and GR
      II actions were inhibited by mifepristone, a GR-II pathway inhibitor. Together
      these data directly link the activity of the vpr gene product to the
      glucocorticoid steroid pathway and provide a biochemical mechanism for the
      cellular and viral activity of Vpr, as well as suggest that a unique class of
      antivirals, which includes mifepristone (RU486), may influence HIV-1 replication.

PMID- 7724609
TI  - Toward an outline of the topography of a realistic protein-folding funnel.
AB  - Experimental information on the structure and dynamics of molten globules gives
      estimates for the energy landscape's characteristics for folding highly helical
      proteins, when supplemented by a theory of the helix-coil transition in collapsed
      heteropolymers. A law of corresponding states relating simulations on small
      lattice models to real proteins possessing many more degrees of freedom results.
      This correspondence reveals parallels between "minimalist" lattice results and
      recent experimental results for the degree of native character of the folding
      transition state and molten globule and also pinpoints the needs of further
      experiments.

PMID- 7724611
TI  - Genetic modulation of sickle cell anemia.
AB  - Sickle cell anemia, a common disorder associated with reduced life span of the
      red blood cell and vasoocclusive events, is caused by a mutation in the beta
      hemoglobin gene. Yet, despite this genetic homogeneity, the phenotype of the
      disease is heterogeneous. This suggests the modulating influence of associated
      inherited traits. Some of these may influence the accumulation of fetal
      hemoglobin, a hemoglobin type that interferes with the polymerization of sickle
      hemoglobin. Another inherited trait determines the accumulation of alpha-globin
      chains. This review focuses on potential genetic regulators of the phenotype of
      sickle cell anemia.

PMID- 7724610
TI  - Activation of the interleukin 6 gene by Mycobacterium tuberculosis or
      lipopolysaccharide is mediated by nuclear factors NF IL 6 and NF-kappa B.

PMID- 7724612
TI  - Low CO2 stimulates inositol phosphate turnover and increased inositol 1,4,5
      trisphosphate levels in piglet cerebral microvascular smooth muscle cells.
AB  - In contrast to hypercapnic dilation, hypocapnia-induced cerebral vasoconstriction
      does not involve prostanoids in newborn pigs. The hypothesis that increased pH or
      decreased CO2 tension increases inositol phosphate turnover in piglet cerebral
      microvascular smooth muscle (SM) cells was addressed to begin to assess the
      possibility that this second-messenger system is involved in hypocapnia-induced
      cerebral vasoconstriction. Cerebral microvascular SM cells in primary culture
      prelabeled with [3H]-myoinositol were stimulated for 30 sec with artificial
      cerebrospinal fluid of increased or normal pH, (7.80 vs 7.40), constant PCO2 36
      mm Hg. Following extraction from cells, radiolabeled inositol phosphates were
      separated by HPLC. These metabolic alkalosis studies were repeated using an
      inositol 1,4,5-trisphosphate (Ins[1,4,5]P3 protein-binding assay (PBA).
      Respiratory alkalosis using aCSF with pH 7.60, PCO2 20 mm Hg versus control pH
      7.40, PCO2 36 mm Hg was similarly tested with PBS measurement of Ins(1,4,5)P3.
      aCSFs of control pH 7.40, and PCO2s of 70, 36, or 25 mm Hg were studied both by
      [3H]-myoinositol (HPLC) and PBA to further determine the importance of CO2
      tension, in the presence of fixed pH, on Ins(1,4,5)P3 production. When PCO2 was
      constant, inositol phosphate turnover (as measured by [3H]-Ins[1,4,5]P3
      accumulation) increased when pH was increased from 7.40 to 7.80 at 30 sec of
      stimulation. Mean [3H]-Ins(1,4,5)P3 accumulation at pHs of 7.40 and 7.80,
      constant PCO2 of 36 mm Hg, were 2.9 +/- 0.7 and 4.1 +/- 0.8 cpm/micrograms
      protein, respectively. Ins(1,4,5)P3 levels for pH of 7.40 or 7.80 and constant
      PCO2 of 36 mm Hg, were 25.4 +/- 1.8 and 38 +/- 8 pmol/well, respectively, by PBA.
      Respiratory alkalosis also increased Ins(1,4,5)P3 levels. For pH of 7.40, PCO2 36
      mm Hg and pH 7.60, PCO2 20 mm Hg, Ins(1,4,5)P3 levels were 37.6 +/- 16 and 64.1
      +/- 25 pmol/well, respectively. Decreasing CO2 tension (from 70 mm Hg to 25 mm
      Hg) in the presence of fixed pH 7.40 failed to increase Ins(1,4,5)P3 levels. The
      present data demonstrate that decreased CO2 tension stimulates an increase in
      Ins(1,4,5)P3 production in piglet cerebral microvascular smooth muscle cells.
      Increasing pH via lower PCO2 increases the level of Ins(1,4,5)P3 even more than
      increasing pH with fixed base, but extracellular pH appears to be important since
      decreased PCO2 without changing extracellular pH had no effect. We conclude that
      the inositol phosphate second messenger system in cerebral microvascular smooth
      muscle responds appropriately to acute alkalosis to be involved in hypocapnia
      induced cerebral vasoconstriction.

PMID- 7724613
TI  - Release of kaliuretic peptide during immersion-induced central hypervolemia in
      healthy humans.
AB  - Kaliuretic peptide, a new peptide hormone consisting of amino acids 79-98 of the
      126 amino acid atrial natriuretic factor (ANF) prohormone, is synthesized in the
      heart and is a potent stimulator of potassium excretion. The mechanism(s)
      controlling the release of kaliuretic peptide heretofore has not been defined.
      Because water immersion to the neck provides an acute central volume expansion
      identical to that produced by 2 liters of saline but without the plasma
      compositional change, immersion to the neck (NI) was utilized to assess
      kaliuretic peptide responses to acute central blood volume expansion in seven
      seated sodium-replete normal subjects. Since atrial natriuretic factor (ANF;
      amino acids 99-126 of the prohormone) originates from the amino acids adjacent to
      kaliuretic peptide in the ANF prohormone but is proteolytically cleaved from the
      rest of the prohormone before release, measurement of ANF was incorporated into
      this study to determine if there are differences with respect to release of these
      two portions of the ANF prohormone. Both kaliuretic peptide and ANF increased
      promptly with NI, with ANF peaking at 1 hr of immersion, whereas kaliuretic
      peptide peaked at the 3rd hr of immersion. With cessation of immersion, ANF
      decreased to preimmersion levels within 0.5 hr while kaliuretic peptide was still
      significantly (P < 0.05) elevated at 1 hr postimmersion. These findings indicate
      that kaliuretic peptide and ANF are released simultaneously but that kaliuretic
      peptide peak circulating concentration and its return to preimmersion values are
      prolonged compared with ANF. These last findings suggest a slower clearance from
      the circulation for kaliuretic peptide. The diuretic peak response to NI
      corresponded in a temporal manner to the peak circulating concentration of
      kaliuretic peptide, suggesting a possible physiologic role for kaliuretic peptide
      in modulating volume homeostasis in humans.

PMID- 7724614
TI  - Humoral factors trophic for vascular smooth muscle during the development of
      hypertension in rats.
AB  - There is evidence that a humoral factor or factors in rats with one-kidney, one
      clip (1K1C) hypertension increase growth of cultured vascular smooth muscle
      cells. Such humoral trophic factors may contribute to the abnormal growth of
      arterial muscle in hypertension. To further study the longitudinal expression of
      this trophic factor or factors, we prepared rats with 1K1C hypertension of
      different durations. To determine if the factor or factors are also expressed in
      other forms of experimental hypertension, we additionally prepared rats with two
      kidney, one-clip (2K1C) hypertension and paired two-kidney (2K) normotensive
      controls; we also studied Spontaneously Hypertensive Rats (SHR) plus appropriate
      controls. In the presence of growth stimulated by background levels (1%) of fetal
      calf serum, 20% platelet-poor, plasma-derived serum (PDS) from 1K1C rats 8-14
      days (n = 10) and 28 days (n = 12) after clipping increased [3H]-thymidine
      incorporation of growth-arrested cultured rat aortic smooth muscle cells more
      than the paired 1K PDS, by up to +67% and +40%, respectively (P < 0.01). However,
      with PDS from 1K1C rats 4 days (n = 11) and 38 days (n = 6) after clipping there
      was no evidence for a differential effect (P > 0.5 and P > 0.1, respectively).
      PDS from seven 2K1C rats (at 9 days) also increased [3H]-thymidine incorporation
      of the assay cells more than PDS from the paired 2K rats, by up to +19% (P <
      0.05). However, there was no evidence that PDS from SHR differentially increased
      cellular thymidine incorporation. Thus, evidence from this study suggests that
      the humoral factor or factors trophic for vascular smooth muscle are expressed in
      both low- and high-renin forms of experimental renovascular hypertension, but not
      in the very early or in the late complicated stages of the hypertension, or in
      genetic hypertension in rats.

PMID- 7724616
TI  - Increased dipsogenic responsiveness to angiotensin II in rats exposed to cold:
      rate of loss after return to thermoneutral ambient temperature.
AB  - Subcutaneous administration of angiotensin II (Ang II) to rats exposed
      chronically to 5 degrees C induced an increased drinking response compared with
      that of warm-acclimated controls. The exaggerated drinking response was also
      observed when graded doses of Ang II were administered into the lateral
      cerebroventricle (icv) of chronically cold-exposed rats. A maximal drinking
      response occurred in cold-treated, but not in control, rats when the lowest dose
      of Ang II (1.6 ng/rat) was administered icv. Thus, it is clear that the
      dipsogenic responsiveness to either centrally or peripherally administered Ang II
      is increased by chronic exposure to cold. To assess whether the increased
      responsiveness was retained after removal from cold, graded doses of Ang II were
      administered to rats removed from cold to a thermoneutral environment. The
      results again showed a maximal responsiveness to the lowest dose of Ang II
      administered (25 micrograms/kg, sc) to cold-treated rats that had either just
      been removed from cold or removed from cold 2 hr prior to treatment. Cold-exposed
      rats had an ED50 for Ang II-induced drinking that was about half that of their
      warm-acclimated controls. To assess how long the cold-induced increase in
      dipsogenic responsiveness to Ang II lasted after return to a thermoneutral
      temperature, rats were removed from cold for 24, 48, or 60 hr and then
      administered graded doses of Ang II (25, 50, or 100 micrograms/kg, sc). The
      results suggest that between 46 and 52 hr after removal from cold, the cold
      induced increase in dipsogenic responsiveness to Ang II returned to the level of
      the controls. Hence, the physiological changes in the dipsogenic mechanism
      induced by exposure to cold are not immediately reversible when the rats are
      returned to a thermoneutral ambient temperature.

PMID- 7724615
TI  - Cloning of the rat ecotropic retroviral receptor and studies of its expression in
      intestinal tissues.
AB  - A long-term goal of our laboratory is to establish a rat model to study the
      feasibility of using the intestinal tract as a site for somatic gene therapy. As
      a step toward that goal, the current study reports the cloning of the rat
      ecotropic retroviral receptor (EcoR) cDNA and the study of various aspects of its
      expression in the intestinal tissues. The cDNA for rat EcoR was cloned by
      screening a size-selected rat intestinal cDNA library with mouse EcoR cDNA. A
      clone of approximately 7 kb, designated MP10, was obtained. Partial sequencing of
      MP10 from the 5' end revealed a level of similarity of 92% compared with mouse
      EcoR. The presence of a 5' untranslated region and a 3' poly(A) tract, together
      with the overall size of the cDNA, suggest that is very close to being a full
      length cDNA for this large transcript. Northern blots with MP10 showed an RNA of
      approximately 7.9 kb present along the entire length of the small intestine and
      somewhat less abundant in the colon. Developmental studies showed high levels of
      EcoR in fetal rat intestine, a decline in the early postnatal period, then a
      gradual rise to adulthood. Caco-2 cells were used to assess the expression of
      EcoR in proliferating compared with differentiated intestinal epithelial cells.
      EcoR mRNA was found to be very much more abundant in nondifferentiated cells and
      declined to low levels as the cells underwent spontaneous differentiation. These
      patterns of EcoR expression indicate that ecotropic retroviruses should be
      suitable vectors with which to attempt gene transfer into the intestinal
      epithelium. In addition, since the endogenous role of EcoR is as the y+ cationic
      amino acid transporter, these data have significance for understanding patterns
      of amino acid transport in the intestinal epithelium.

PMID- 7724617
TI  - Growth in iron-deficient rats.
AB  - Poor growth in iron deficiency is commonly observed in animal studies. Previous
      studies from our laboratory showed that iron-deficient rats are metabolically
      inefficient and have less body fat than controls and proposed that iron
      deficiency was related to increased metabolic rates and heat loss. To examine
      these points more completely, we examined growth and metabolic rate of iron
      deficient rats at two environmental temperatures, 25 degrees C and 32 degrees C,
      and feed efficiency in separate groups of rats during a period of rapid growth.
      Iron deficiency (hemoglobin [Hb] approximately 60 g/liter) was associated with a
      systematic elevation of metabolic rate over the 24-hr day with animals at 25
      degrees C. This did not occur in animals living in thermoneutrality. Iron
      deficiency affected growth of animals at 25 degrees C but not at 32 degrees C.
      Feed efficiency (kcal retained/kcal absorbed) was 25 +/- 4.2 and 31 +/- 4.9 kcal
      (P < 0.0001), respectively, in iron deficient rats and animals were not anorexic.
      Use of food-restricted animals allowed the direct calculation that iron
      deficiency was associated with a 10%-15% increase requirement for growth. We
      conclude that iron deficiency anemia is associated with a poor feed efficiency
      and that it is attenuated when nonshivering thermogenesis is minimized by a
      thermoneutral environment.

PMID- 7724619
TI  - 5-Hydroxytryptaminergic receptor-stimulated growth hormone secretion occurs
      independently of changes in peripheral somatostatin concentration.
AB  - Effects of activation or blockade of 5-hydroxytryptaminergic receptors on
      concentrations of growth hormone and somatostatin in serum were studied in
      Holstein steers (mean +/- SEM: 159 +/- 8 days of age; 160 +/- 9 kg of body wt). A
      pelleted diet was available ad libitum between 1000 and 1200 hr each day. Blood
      was sampled from a cannula in a jugular vein. Peak concentration of growth
      hormone in serum within 1 hr before feeding (12.8 +/- 3.8 ng/ml) was greater than
      peak concentration within 1 hr after removal of feed (3.3 +/- 1.0 ng/ml). In
      contrast, concentration of somatostatin in plasma did not change from 1 hr before
      feeding through 1 hr after removal of feed (47.3 to 43.0 +/- 4.5 pg/ml). Relative
      to saline-injected controls, activation of 5-hydroxytryptaminergic receptors with
      quipazine (0.5, 0.1, and 0.2 mg/kg body wt, iv) increased the area under growth
      hormone response curves 5.5- to 25-fold before and after feeding. In another
      experiment, injection of 0.1 mg of quipazine/kg body wt at 1300 hr increased the
      concentration of growth hormone in serum 7.8-fold compared with controls, but had
      no effect on concentration of somatostatin in plasma. Relative to water-injected
      controls, blockade of 5-hydroxytryptaminergic receptors with cyproheptadine (0.2
      mg/kg body wt, sc) decreased the area under growth hormone response curves for at
      least 110 min before feeding (71%) and after removal of feed (69%). The data
      support the hypothesis that 5-hydroxytryptaminergic receptors are involved in
      stimulation of pulsatile growth hormone secretion in meal-fed cattle. Lack of a
      change in concentration of somatostatin in plasma with respect to time of meal
      feeding or after injection of the 5-hydroxytryptaminergic-receptor agonist
      quipazine suggests that 5-hydroxytryptaminergic receptor-stimulated growth
      hormone secretion is likely mediated within the central nervous system, rather
      than by meal-induced changes in peripheral secretion of somatostatin.

PMID- 7724618
TI  - Transformation of primary cultures of shrimp (Penaeus stylirostris) lymphoid
      (Oka) organ with Simian virus-40 (T) antigen.
AB  - Primary cultures of lymphoid (Oka) organ from Penaeus stylirostris were
      transformed with naked or Lipofectin-mediated pSV-3 neo, a shuttle vector
      containing the tumor (T) antigen gene from Simian virus-40. The transformed
      cells, OKTr-1 and OKTr-23, exhibited the following characteristics: rounded
      morphology forming grapelike aggregates, loosely adhesive, increased growth rate
      in Medium-199, resistance to G-418 (a neomycin analog marker in the shuttle
      vector), cloning efficiencies of 68.7% and 36.7% in soft agarose, respectively,
      and stability in liquid nitrogen storage. Immunofluorescence staining (IFA) of
      the transformed cells using a monoclonal antibody against SV-40 tumor antigen
      showed positive results. In contrast, primary cell cultures exhibited fibroblast
      like morphology and formed a tight, adhesive monolayer on the surface of the
      culture vessel. They were sensitive to G-418, and showed negative results with
      IFA. To date, OKTr-1 and OKTr-23 have undergone 44 and 18 passages, respectively.
      Primary cultures of the lymphoid organ have not been successfully passaged beyond
      the primary stage.

PMID- 7724621
TI  - [Apprenticeship of nursing students. Accreditation criteria].

PMID- 7724620
TI  - Myosin heavy chain gene expression in bovine fetuses and neonates representing
      genotypes with contrasting patterns of growth.
AB  - Fetal and neonatal myosin heavy chain (MHC) gene expression was examined in
      bovine genotypes that differed in their postnatal growth pattern and mature size.
      Pregnancies were established that would be expected to produce early-,
      intermediate-, or late-maturing postnatal growth. Fetal skeletal and cardiac
      muscles were collected at 100 and 200 days of gestation and at 30 days of age.
      Muscle tissue was analyzed for relative levels of MHC RNA and protein.
      Longissimus muscle MHC RNA/microgram RNA was greater at the 100-day time point
      for the intermediate maturity type (P < 0.05), which differed from the 200-day
      time point where the early maturity type had the greater RNA level (P < 0.05).
      Triceps muscle MHC RNA/microgram RNA weights differed due to genotype at 200 days
      gestation but did not differ at 100 days gestation or at 30 days postnatal.
      Ventricular muscle MHC RNA did not differ due to genotype at any of the three
      developmental stages. Differences due to maturity type in MHC protein/mg DNA were
      observed at 30 days of age, but no differences due to maturity type were observed
      at the prenatal time points. These results indicate that bovine fetal skeletal
      muscle MHC RNA production can be influenced by genotype and that genotype may be
      an important factor for future studies examining the role of external influences
      on fetal muscle growth.

PMID- 7724622
TI  - [Nursing practice as a free profession: is society ready for it?].

PMID- 7724623
TI  - [Protocol for total parenteral nutrition at home. Personal experiences].

PMID- 7724624
TI  - [Gigi Ghirotti: neoplastic disease within the walls of home].

PMID- 7724626
TI  - Nurse and patient perceptions of pain.
AB  - Patient pain is a problem frequently encountered by nurses, who are often
      directly responsible for its management. Accurate pain assessment is vital for
      appropriate management. The nurse's role in pain control should evolve to one of
      empowering patients to determine the management of their own pain where possible.

PMID- 7724625
TI  - Accountability in practice.

PMID- 7724628
TI  - The relationship between obesity, dieting and eating disorders.
AB  - Obesity is not only a major health problem in Western society. It is also a
      social and personal one. Staying on a diet demands constant self-control. Failure
      to stay on a diet causes stress to dieters. Unsuccessful dieting could be more
      harmful than not dieting at all.

PMID- 7724629
TI  - The nurse's role in giving nutritional advice.
AB  - Nurses are ideally placed to advise on nutrition and diet. Using the principles
      of the nursing process, nurses can assess clients, plan and help them implement
      changes in diet and evaluate the results. Everyday language should be used and
      practical advice must be given.

PMID- 7724630
TI  - The care of patients with dementia in general wards.
AB  - More people are surviving into old age. General nurses should therefore be
      prepared to care for increasing numbers of patients with dementia. Nurses must
      understand the problems of dementia and how these are made worse by
      hospitalisation. Good care is founded on thorough assessment of the patient's
      problems, needs and abilities.

PMID- 7724627
TI  - Assessing counselling skills in nurse education.
AB  - Nurses frequently employ counselling skills in their work. Competent practice in
      counselling is achieved by self-exploration, supervised work, acquiring skills
      and the study of theory. Competence can be assessed by trainers, managers,
      supervisers, external judges, peers, the counsellor or the client.

PMID- 7724631
TI  - Infusion devices: volumetric and peristaltic pumps.
AB  - Infusion pumps are an essential part of any acute unit's equipment. But as such
      pumps become increasingly sophisticated, selecting the appropriate machine has
      become a more difficult task. Infusion pumps are expensive, and it is essential
      to balance the features required with the investment made.

PMID- 7724632
TI  - Toxoplasmosis and pregnant women.
AB  - Screening pregnant women should reduce the incidence of toxoplasmosis. Education
      of midwives and the public is a prime factor in prevention.

PMID- 7724633
TI  - Patients' experiences of chemotherapy treatment.
AB  - Patients' views on chemotherapy should always be obtained. Vomiting and, in
      particular, nausea remain significant problems for individuals receiving
      cisplatin-based chemotherapy. Home chemotherapy may reduce the life disruption of
      those receiving chemotherapy.

PMID- 7724634
TI  - Developing a philosophy for nursing practice.
AB  - Establishing a nursing philosophy is the first step in achieving an integrated
      approach to nursing care provision. A nursing philosophy should reflect the
      beliefs and values of the whole nursing team. It should be realistic and
      manifested through nursing action. Implementing change in professional practice
      requires thorough planning. This encompasses identifying and involving the target
      group and selecting the most appropriate strategy.

PMID- 7724635
TI  - The use of erythropoietin to treat anaemia in end-stage renal disease.
AB  - Recombinant human erythropoietin (r-HuEPO) has greatly improved the lives of
      renal patients with anaemia. Nurses who administer r-HuEPO should be aware of its
      side-effects. Studies are still needed to elicit the most efficient route of
      administration of r-HuEPO.

PMID- 7724636
TI  - More and more pieces of equipment are labelled 'disposable' or 'single use only'.

PMID- 7724637
TI  - Injections.
AB  - An update on injection techniques, with a review of their indications, choice of
      routes and ideal sites. A discussion of potential complications for the patient
      and practitioner is also provided.

PMID- 7724638
TI  - Wound dressings on the Drug Tariff.
AB  - Nurses in the community need to be aware of the range of dressings available.
      Hospital nurses also need this knowledge to inform discharge planning.

PMID- 7724639
TI  - Fear of acquiring HIV is receding.

PMID- 7724640
TI  - Ward sisters' influence on use of care plans.
AB  - The ward sister's influence affects nurses' attitudes to care plans. This
      influence may be positive or negative. There may be other factors that affect
      nurses' attitudes to care plans, which should be addressed in future research.

PMID- 7724641
TI  - The implications of PREP for practitioners.
AB  - The UKCC's proposals for PREP take effect on April 1, 1995. There are three major
      proposals: preceptor support; maintenance of effective registration and standard
      setting for post-registration courses. There are four requirements for
      maintaining effective registration: notification of practice; return to practice
      programmes; five days of study every three years; and professional profiling.

PMID- 7724642
TI  - Molecular neurobiology. Mechanisms common to brain, skin and immune system.
      Proceedings of the International Symposium on Molecular Neurobiology. Tokyo,
      November 1992.

PMID- 7724643
TI  - The cadherin cell adhesion receptor family: roles in multicellular organization
      and neurogenesis.

PMID- 7724645
TI  - Trophic interactions at developing synapses.

PMID- 7724644
TI  - Pharmacologic regulation of striatal proenkephalin gene expression via
      transcription factor CREB.

PMID- 7724646
TI  - Cytokines and graft-V-host disease.

PMID- 7724647
TI  - Nerve-skin interactions in adult and aged animals.

PMID- 7724648
TI  - Nerve and mast cell interaction: cell conflict or information exchange?

PMID- 7724649
TI  - Neurotrophins: a family of proteins supporting the survival of neurons.
AB  - NGF, BDNF, NT-3, and NT-4/5 are all members of a structurally related family of
      molecules that function to prevent the death of embryonic neurons during
      development. The presence of these molecules in the targets of innervating
      neurons is likely to explain at least in part why many neurons depend on their
      target tissues for survival. A small family of related membrane proteins with a
      ligand-activable tyrosine kinase and expressed in the nervous system represents a
      significant part of the structural basis explaining how neurons discriminate
      between the neurotrophins and transduce the consequence of neurotrophin binding.
      Thus, much structural information has been obtained that contributes to better
      understand some important aspects of vertebrate neurogenesis, particularly those
      related to selective cell survival in a very diverse cellular system like the
      nervous system. Future studies will have to explain how the role of these
      molecules has to be understood in the context of the characteristic features of
      the nervous system, in particular neurotransmission and electrical activity.
      Finally, while the role of neurotrophins has been discussed here in the context
      of the developing nervous system, it will be important to understand what
      functions these molecules might play in the central nervous system. For example,
      neurotrophins might function as long term mediators of changes in cellular shapes
      under the influence of electrical activity, as well as in pathological situations
      when axonal elongation is needed to restore connections, or to maintain the well
      being of neurons that are eliminated during the course of neurodegenerative
      diseases.

PMID- 7724650
TI  - Gene targeting: a new approach for the analysis of mammalian memory and learning.

PMID- 7724651
TI  - The involvement of amyloid associated proteins in the formation of beta-protein
      filaments in Alzheimer's disease.

PMID- 7724653
TI  - The molecular diversity of glutamate receptors.

PMID- 7724652
TI  - Odorant receptor diversity and patterned gene expression in the mammalian
      olfactory epithelium.
AB  - The mammalian olfactory system is capable of discriminating a vast array of
      structurally diverse odors. We have identified a novel multigene family whose
      unusual size and diversity suggest that odor discrimination may rely heavily on
      the existence of many hundreds of different types of odorant receptors which are
      differentially expressed by olfactory sensory neurons in the nasal cavity. We
      have found that the members of this family are segregated in their expression
      into a series of distinct, and highly specified, zones within the olfactory
      epithelium. Our experiments suggest that the odorant receptor expression zones
      may provide for an initial organization of sensory information in the nasal
      cavity which is maintained in the transmission of this information to the
      olfactory bulb of the brain.

PMID- 7724654
TI  - Function and mode of action of small G protein.

PMID- 7724655
TI  - Regulation of the early development of the nervous system by growth factors.
AB  - Development of the nervous system, although patterned by intrinsic genetic
      expression, appears to be dependent on growth factors for many of the
      differentiation steps that generate the wide variety of neurons and glia found in
      the both the central and peripheral nervous system. By using in vitro assays,
      including clonal analysis, the precise function of the various growth factors and
      the differentiation potential of the various neural populations has begun to be
      described. This review discusses some of the recent findings and examines how
      neuronal differentiation may result from the interaction of several growth
      factors.

PMID- 7724656
TI  - Calcium signalling in platelets and other nonexcitable cells.
AB  - By virtue of their biological simplicity and widespread availability, platelets
      frequently have been used as a model system to study signal transduction. Such
      studies have revealed that changes in intracellular free calcium concentration
      are central to platelet functioning. The following article reviews current
      concepts of platelet structure and function, with particular emphasis on the
      mechanisms involved in platelet Ca2+ signalling.

PMID- 7724657
TI  - Purinoceptors: are there families of P2X and P2Y purinoceptors?
AB  - There has been an exponential growth in interest in purinoceptors since the
      potent effects of purines were first reported in 1929 and purinoceptors defined
      in 1978. A distinction between P1 (adenosine) and P2 (ATP/ADP) purinoceptors was
      recognized at that time and later, A1 and A2, as well as P2x and P2y subclasses
      of P1 and P2 purinoceptors were also defined. However, in recent years, many new
      subclasses have been claimed, particularly for the receptors to nucleotides,
      including P2t, P2z, P2u(n) and P2D, and there is some confusion now about how to
      incorporate additional discoveries concerning the responses of different tissues
      to purines. The studies beginning to appear defining the molecular structure of
      P2-purinoceptor subtypes are clearly going to be important in resolving this
      problem, as well as the introduction of new compounds that can discriminate
      pharmacologically between subtypes. Thus, in this review, on the basis of this
      new data and after a detailed analysis of the literature, we propose that: (1)
      P2X(ligand-gated) and P2Y(G-protein-coupled) purinoceptor families are
      established; (2) four subclasses of P2X-purinoceptor can be identified (P2X1
      P2X4) to date; (3) the variously named P2-purinoceptors that are G-protein
      coupled should be incorporated into numbered subclasses of the P2Y family. Thus:
      P2Y1 represents the recently cloned P2Y receptor (clone 803) from chick brain;
      P2Y2 represents the recently cloned P2u (or P2n) receptor from neuroblastoma,
      human epithelial and rat heart cells; P2Y3 represents the recently cloned P2Y
      receptor (clone 103) from chick brain that resembles the former P2t receptor;
      P2Y4-P2Y6 represent subclasses based on agonist potencies of newly synthesised
      analogues; P2Y7 represents the former P2D receptor for dinucleotides. This new
      framework for P2 purinoceptors would be fully consistent with what is emerging
      for the receptors to other major transmitters, such as acetylcholine, gamma
      aminobutyric acid, glutamate and serotonin, where two main receptor families have
      been recognised, one mediating fast receptor responses directly linked to an ion
      channel, the other mediating slower responses through G-proteins. We fully expect
      discussion on the numbering of the different receptor subtypes within the P2X and
      P2Y families, but believe that this new way of defining receptors for
      nucleotides, based on agonist potency order, transduction mechanisms and
      molecular structure, will give a more ordered and logical approach to
      accommodating new findings. Moreover, based on the extensive literature analysis
      that led to this proposal, we suggest that the development of selective
      antagonists for the different P2-purinoceptor subtypes is now highly desirable,
      particularly for therapeutic purposes.

PMID- 7724658
TI  - Oral rehydration therapy.
AB  - Oral rehydration therapy (ORT) with glucose-electrolyte solutions has been
      considered to be one of the greatest therapeutic advances of this century. ORT is
      effective in acute diarrheal disease of diverse etiology. The most widely used
      oral rehydration solution (ORS) worldwide is that recommended by the World Health
      Organisation (Na 90, K 20, glucose 111 and citrate 10 mmol/L). Attempts to
      improve the efficacy of ORS have been made by using complex substrates (rice and
      other cereals) in place of glucose, and by reducing osmolality by decreasing
      glucose and sodium concentrations in monomeric ORS. ORS may have wider
      applications in the management of patients with the short bowel syndrome and in
      post-surgical patients.

PMID- 7724659
TI  - Intracellular Ca2+ release in cerebral arteries.
AB  - Vasoconstricting agonists elevate the intracellular Ca2+ concentration and induce
      tension development in vascular smooth muscle cells by inducing both Ca2+ influx
      from the extracellular space and Ca2+ release from cellular stores. The relative
      importance of Ca2+ release has been found to vary between different sites in the
      vasculature. This review examines the role of Ca2+ release in the activation of
      cerebral arteries produced by several vasoconstricting stimuli. Although the
      activation of cerebral arteries by agonists such as 5-hydroxytryptamine and
      noradrenaline has typically been found to have little dependence on Ca2+ release,
      other vasoconstrictors such as thromboxane A2, which may be released from the
      endothelium by other agonists, appear to induce a substantial intracellular Ca2+
      release in cerebral arteries. The limited efficacy of Ca2+ influx blockers in the
      treatment of delayed cerebrovascular constriction occurring as a result of
      subarachnoid haemorrhage suggests that intracellular mechanisms such as Ca2+
      release and/or the activation of protein kinase C may be important determinants
      of vasoconstriction under pathological conditions.

PMID- 7724660
TI  - A review of stonefish venoms and toxins.
AB  - Venoms from stonefish (genus Synanceja) have marked effects on the cardiovascular
      and neuromuscular systems and on vascular permeability; the venoms also exhibit
      haemolytic and hyaluronidase activity. Recently, a toxic protein, stonustoxin
      (SNTX), was purified from the venom of S. horrida: the primary lethal action of
      SNTX has been attributed to its potent endothelium-dependent vasorelaxant
      activity causing a rapid, marked and irreversible hypotension; the other actions
      of SNTX resemble those of the stonefish crude venoms.

PMID- 7724661
TI  - Coley's toxins, tumor necrosis factor and cancer research: a historical
      perspective.
AB  - As far back as the 1700s, it was recorded that certain infectious disease
      processes could exert a beneficial therapeutic effect upon malignancy. Most
      prominent among the numerous deliberate efforts made to take advantage of these
      observations was that of a pioneering New York surgeon, William B. Coley, active
      career 1891-1936. Using a bacterial vaccine to treat primarily inoperable
      sarcoma. Coley accomplished a cure rate of better than 10%. This review examines
      the history of these efforts and presents a discussion of their corresponding
      relevance to present day immunotherapy.

PMID- 7724662
TI  - Humoral thermogenesis and its role in maintaining energy balance.

PMID- 7724663
TI  - ATP-dependent transport systems in the canalicular membrane of the hepatocyte.

PMID- 7724665
TI  - Influence of extraocular muscle proprioception on vision.

PMID- 7724664
TI  - Neuropeptides as regulators of airway function: vasoactive intestinal peptide and
      the tachykinins.

PMID- 7724666
TI  - Acetylcholine receptor gene expression at the developing neuromuscular junction.

PMID- 7724667
TI  - Vesicular neurotransmitter transporters: from bacteria to humans.

PMID- 7724668
TI  - The septohippocampal pathway: structure and function of a central cholinergic
      system.

PMID- 7724669
TI  - A beta-glucosidase from lodgepole pine xylem specific for the lignin precursor
      coniferin.
AB  - Coniferin, the glucoside of the monolignol coniferyl alcohol, accumulates to high
      levels in gymnosperms during spring-cambial reactivation. A cinnamyl alcohol
      glucoside/beta-glucosidase system is thought to play a key role in lignification
      by releasing the monolignol aglycones. Investigation of such an enzyme system in
      the xylem of Pinus contorta var latifolia Engelm. revealed two major beta
      glucosidases. One efficiently hydrolyzed the native substrate, coniferin, and the
      other was more active against synthetic glucosides. The coniferin beta
      glucosidase was purified to apparent homogeneity using anion exchange,
      hydrophobic interaction, and size-exclusion chromatography. The apparent native
      molecular weight was estimated to be 60,000. A dominant 28-kD protein and a minor
      24-kD protein were detected in the purified preparation following sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Immunological evidence from
      polyclonal antibodies directed against the synthetic N-terminal peptide of the 24
      kD protein suggested that the native protein is a dimer of 28-kD subunit size.
      The N-terminal sequence showed that coniferin beta-glucosidase has high homology
      to known plant beta-glucosidases. Coniferin, syringin, and a synthetic coniferin
      analog were preferred substrates for the coniferin beta-glucosidase. In situ
      localization using the chromogenic coniferin analog showed the exclusive presence
      of beta-glucosidase activity in the differentiating xylem, similar to peroxidase
      activity.

PMID- 7724670
TI  - RML1 and RML2, Arabidopsis genes required for cell proliferation at the root tip.
AB  - New cells are produced from the meristematic tissues located at the shoot and
      root tip throughout the life of higher plants. To investigate the genetic
      mechanism regulating meristematic activity, we isolated and characterized four
      single-gene, recessive mutants in Arabidopsis thaliana called root meristemless
      (rml). Complementation tests identified two RML loci; RML1 maps to chromosome IV
      and RML2 maps to chromosome III. These mutants produce normal embryonic roots
      that either did not undergo or experienced limited cell division following
      germination, resulting in primary roots of less than 2.0 mm in length. Mutants
      can produce lateral and adventitious roots, which can grow to a length comparable
      to the embryonic root and arrest, indicating that the growth arrest is unrelated
      to the embryonic dormancy process. Neither the addition of growth regulators to
      the media nor the removal of shoots can rescue mutant roots from growth arrest,
      indicating that the mutant phenotype is not caused by a shortage of known growth
      regulators or by a transmissible shoot inhibitor. Normal cell division ability in
      mutant embryo, shoot, and callus cells indicates that the RML gene functions are
      not part of the general cell division processes; rather, they are involved
      specifically in activating the cell division cycle in the root apical cells.

PMID- 7724672
TI  - Immunoaffinity purification and comparison of allantoinases from soybean root
      nodules and cotyledons.
AB  - Allantoinase (allantoin amidohydrolase, EC 3.5.2.5) catalyzes the conversion of
      allantoin to allantoic acid in the final step of ureide biogenesis. We have
      purified allantoinase more than 4000-fold by immunoaffinity chromatography from
      root nodules and cotyledons of soybean (Glycine max [L] Merr.). We characterized
      and compared properties of the enzyme from the two sources. Seed and nodule
      allantoinases had 80% identity in the first 24 amino acid residues of the N
      terminus. Two-dimensional gel electrophoresis of the purified enzymes showed that
      multiple forms were present in each. Allantoinases from nodules and cotyledons
      had very low affinity for allantoin with a Km for allantoin of 17.3 mM in
      cotyledons and 24.4 mM in nodules. Both had activity in a broad range of pH
      values from 6.5 to 7.5. In addition, purified allantoinase from both sources was
      very heat stable. Enzyme activity was stable after 1 h at 70 degrees C, decreased
      gradually with heating to 85 degrees C, and was lost at 90 to 95 degrees C.
      Although these studies have revealed some differences between allantoinases in
      seeds and nodules, the differences were not reflected in key enzyme properties.
      The immunoaffinity approach enabled purification of allantoinase from soybean
      root nodules and simplified its purification from cotyledons, thereby allowing
      characterization and comparison of the enzyme from the two sources.

PMID- 7724671
TI  - Purification and cDNA isolation of chloroplastic phosphoglycerate kinase from
      Chlamydomonas reinhardtii.
AB  - Chloroplastic phosphoglycerate kinase (PGK) was purified to homogeneity from a
      soluble fraction of chloroplasts of a cell-wall-deficient mutant strain of
      Chlamydomonas reinhardtii (cw-15) using ammonium sulfate fractionation, Reactive
      Blue-72 column chromatography, and native polyacrylamide gel electrophoresis. PGK
      activity was attributed to a single polypeptide with a molecular mass of 42 kD.
      Relative purity and identity of the isolated enzyme was confirmed by N-terminal
      amino acid sequence determination. Antiserum against this enzyme was raised and a
      western blot analysis of whole-cell lysate from cw-15 cells using this anti
      chloroplastic PGK serum detected a single polypeptide with a molecular mass of 42
      kD. The cDNA clone corresponding to the Chlamydomonas chloroplastic PGK was
      isolated from a Chlamydomonas cDNA expression library using the anti-PGK serum.
      The cDNA sequence was determined and apparently codes for the entire precursor
      peptide, which consists of 461 codons. The results from Southern and northern
      blot analyses suggest that the chloroplastic PGK gene exists as a single copy in
      the nuclear genome of C. reinhardtii and is expressed as a 1.8-kb transcript. The
      C. reinhardtii chloroplastic PGK cDNA has 71 and 66% homology with wheat
      chloroplastic PGK and spinach chloroplastic PGK, respectively. Based on the
      deduced amino acid sequence, the chloroplastic PGK of C. reinhardtii has more
      similarity to plant PGKs than to other PGKs, having both prokaryotic and
      eukaryotic features.

PMID- 7724673
TI  - Analysis of the pigment stoichiometry of pigment-protein complexes from barley
      (Hordeum vulgare). The xanthophyll cycle intermediates occur mainly in the light
      harvesting complexes of photosystem I and photosystem II.
AB  - The carotenoid zeaxanthin has been implicated in a nonradiative dissipation of
      excess excitation energy. To determine its site of action, we have examined the
      location of zeaxanthin within the thylakoid membrane components. Five pigment
      protein complexes were isolated with little loss of pigments: photosystem I
      (PSI); core complex (CC) I, the core of PSI; CC II, the core of photosystem II
      (PSII); light-harvesting complex (LHC) IIb, a trimer of the major light
      harvesting protein of PSII; and LHC IIa, c, and d, a complex of the monomeric
      minor light-harvesting proteins of PSII. Zeaxanthin was found predominantly in
      the LHC complexes. Lesser amounts were present in the CCs possibly because these
      contained some extraneous LHC polypeptides. The LHC IIb trimer and the monomeric
      LHC II a, c, and d pigment-proteins from dark-adapted plants each contained, in
      addition to lutein and neoxanthin, one violaxanthin molecule but little
      antheraxanthin and no zeaxanthin. Following illumination, each complex had a
      reduced violaxanthin content, but now more antheraxanthin and zeaxanthin were
      present. PSI had little or no neoxanthin. The pigment content of LHC I was
      deduced by subtracting the pigment content of CC I from that of PSI. Our best
      estimate for the carotenoid content of a LHC IIb trimer from dark-adapted plants
      is one violaxanthin, two neoxanthins, six luteins, and 0.03 mol of antheraxanthin
      per mol trimer. The xanthophyll cycle occurs mainly or exclusively within the
      light-harvesting antennae of both photosystems.

PMID- 7724674
TI  - Light-regulated and organ-specific expression of types 1, 2, and 3 light
      harvesting complex b mRNAs in Ginkgo biloba.
AB  - In a prior study (E. Chinn and J. Silverthorne [1993] Plant Physiol 103: 727-732)
      we showed that the gymnosperm Ginkgo biloba was completely dependent on light for
      chlorophyll synthesis and chloroplast development and that expression of light
      harvesting complex b (Lhcb) mRNAs was substantially increased by light. However,
      dark-grown seedlings that were transferred to constant white light took
      significantly longer than angiosperm seedlings to initiate a program of
      photomorphogenesis and the stems failed to green completely. We have prepared
      type-specific probes for mRNAs encoding major polypeptides of light-harvesting
      complex II (Lhcb1, Lhcb2, and Lhcb3) and have used these to analyze the
      expression of individual Lhcb mRNAs during greening. All three sequences
      accumulated in the top portions of dark-grown seedlings transferred to light,
      but, as was seen previously for total Lhcb mRNAs, there was a transient,
      reproducible decline in the levels of all three mRNAs after 4 d in the light.
      This transient decrease in Lhcb mRNA levels was not paralleled by a decrease in
      Chl accumulation. By contrast, there were significantly lower levels of all three
      Lhcb mRNAs in the lower portions of greening dark-grown stems as well as lower
      Chl levels. We conclude that although the tops of the plants have the capacity to
      etiolate and green, Gingko seedling stems continue a program of development into
      woody tissue in darkness that precludes greening when the seedlings are
      transferred to the light.

PMID- 7724675
TI  - Near-isogenic lines of maize differing for glycinebetaine.
AB  - A series of near-isogenic glycinebetaine-containing and -deficient F8 pairs of
      Zea mays L. (maize) lines were developed. The pairs of lines differ for
      alternative alleles of a single locus; the wild-type allele conferring
      glycinebetaine accumulation is designated Bet1 and the mutant (recessive) allele
      is designated bet1. The near-isogenic lines were used to investigate whether
      glycinebetaine deficiency affects the pool size of the glycinebetaine precursor,
      choline, using a new method for glycinebetaine and choline determination: stable
      isotope dilution plasma desorption mass spectrometry. Glycinebetaine deficiency
      in maize was associated with a significant expansion of the free choline pool,
      but the difference in choline pool size was not equal to the difference in
      glycinebetaine pool size, suggesting that choline must down-regulate its own
      synthesis. Consistent with this, glycinebetaine deficiency was also associated
      with the accumulation of the choline precursor, serine. A randomly amplified
      polymorphic DNA marker was identified that detects the bet1 allele. In 62 F8
      families tested the 10-mer primer 5'-GTCCTCGTAG produced a 1.2-kb polymerase
      chain reaction product only when DNA from Bet1/bet1 or bet1/bet1 lines was used
      as template. All 26 homozygous Bet1/Bet1 F8 families tested were null for this
      marker.

PMID- 7724676
TI  - Ascorbate peroxidase cDNA from maize.

PMID- 7724677
TI  - Molecular cloning of the gene (SodCc1) that encodes a cytosolic copper/zinc
      superoxide dismutase from rice (Oryza sativa L.).

PMID- 7724678
TI  - A cDNA clone for an ATP-sulfurylase from Arabidopsis thaliana.

PMID- 7724679
TI  - The gdcsPA gene from Flaveria pringlei (Asteraceae).

PMID- 7724680
TI  - Nucleotide sequence of a cDNA clone from Arabidopsis thaliana encoding a small A
      T tract-binding protein.

PMID- 7724681
TI  - A second cell wall acid invertase gene in Arabidopsis thaliana.

PMID- 7724682
TI  - Cloning and sequencing of a second ribosome-inactivating protein gene from maize
      (Zea mays L.).

PMID- 7724683
TI  - RNA editing of the mitochondrial atpA/atp9 co-transcript of triticale, carrying
      the timopheevi cytoplasmic male sterility cytoplasm from wheat.

PMID- 7724684
TI  - The glycinin A3B4 mRNA from wild soybean Glycine soja Sieb. et ZUCC.

PMID- 7724685
TI  - Nucleotide sequence of a cDNA clone encoding an acidic laccase from sycamore
      maple (Acer pseudoplatanus L.).

PMID- 7724686
TI  - Molecular cloning and nucleotide sequence of a lipoxygenase cDNA from ripening
      tomato fruit.

PMID- 7724687
TI  - A contrarian view of the five-factor approach to personality description.
AB  - The 5-factor approach (FFA) to personality description has been represented as a
      comprehensive and compelling rubric for assessment. In this article, various
      misgivings about the FFA are delineated. The algorithmic method of factor
      analysis may not provide dimensions that are incisive. The "discovery" of the
      five factors may be influenced by unrecognized constraints on the variable sets
      analyzed. Lexical analyses are based on questionable conceptual and
      methodological assumptions, and have achieved uncertain results. The
      questionnaire version of the FFA has not demonstrated the special merits and
      sufficiencies of the five factors settled upon. Serious uncertainties have arisen
      in regard to the claimed 5-factor structure and the substantive meanings of the
      factors. Some implications of these problems are drawn.

PMID- 7724688
TI  - Solid ground in the wetlands of personality: a reply to Block.
AB  - The five-factor model (FFM) of personality offers a structural organization of
      personality traits in terms of 5 broad factors. J. Block's (1995) critique of the
      FFM failed to recognize the utility of a trait taxonomy and the intent of
      research designed to test the 5-factor hypothesis. In a number of instances he
      omitted reference to empirical evidence that addresses concerns he raised; this
      evidence shows strong support for the FFM beyond the lexical and questionnaire
      traditions he reviews. Many of his suggestions for improving the quality of
      personality research are valuable, but are likely to be more fruitful when used
      in conjunction with established knowledge about the structure of personality
      traits: the FFM.

PMID- 7724689
TI  - So what do you propose we use instead? A reply to Block.
AB  - Unfortunately, Block's brilliant critique is terribly biased, much like a legal
      brief that presents only one side of the issues at suit. It does not distinguish
      between the Big Five model of phenotypic personality attributes from alternative
      models of the causal underpinnings of personality differences. Ironically, it
      attempts to explain away the extensive evidence for the Big Five model as largely
      the result of data prestructuring, with no acknowledgement of the unique
      contribution of the lexical approach to minimizing such problems. Even more
      seriously, it omits a good deal of crucial evidence favorable to the Big Five
      model, including studies of Block's own Q-set and independent investigations of
      personality-related terms in other languages. Sadly, Block's closing suggestions
      provide little in the way of specific proposals for alternatives that he would
      have us use instead.

PMID- 7724690
TI  - Magnitude of sex differences in spatial abilities: a meta-analysis and
      consideration of critical variables.
AB  - In recent years, the magnitude, consistency, and stability across time of
      cognitive sex differences have been questioned. The present study examined these
      issues in the context of spatial abilities. A meta-analysis of 286 effect sizes
      from a variety of spatial ability measures was conducted. Effect sizes were
      partitioned by the specific test used and by a number of variables related to the
      experimental procedure in order to achieve homogeneity. Results showed that sex
      differences are significant in several tests but that some intertest differences
      exist. Partial support was found for the notion that the magnitude of sex
      differences has decreased in recent years. Finally, it was found that the age of
      emergence of sex differences depends on the test used. Results are discussed with
      regard to their implications for the study of sex differences in spatial
      abilities.

PMID- 7724691
TI  - Selection and related threats to group comparisons: an example comparing
      factorial structures of higher and lower ability groups of adult twins.
AB  - Is it possible to construct valid explanations of behavioral phenomena from
      differences found among naturally existing groups? Many of psychology's cherished
      findings in such domains as intellectual performance and temperament rest on
      differences of this kind. A venerable and rich literature on selection and
      selection effects both reminds us that naturally existing groups might or might
      not derive from a common parent population and warns that valid decisions between
      these alternatives are often jeopardized by the very methods on which those
      decisions rest. We examine these matters within the context of intellectual
      performance, illustrate key points with an analysis of data, and examine the
      implications for current research on differences in ability levels.

PMID- 7724692
TI  - Depression and memory impairment: a meta-analysis of the association, its
      pattern, and specificity.
AB  - The existing evidence paints an unclear picture of whether an association exists
      between depression and memory impairment. The purpose of this investigation was
      to determine whether depression is associated with memory impairment, whether
      moderator variables determine the extent of this association, and whether any
      obtained association is unique to depression. Meta-analytic techniques were used
      to synthesize data from 99 studies on recall and 48 studies on recognition in
      clinically depressed and nondepressed samples. Associations between memory
      impairment and other psychiatric disorders (e.g., schizophrenia, dementia) were
      also examined. A significant, stable association between depression and memory
      impairment was revealed. Further analyses indicated, however, that it is likely
      that depression is linked to particular aspects of memory, the linkage is found
      in particular subsets of depressed individuals, and memory impairment is not
      unique to depression.

PMID- 7724693
TI  - Temporal factors in the effect of restraint stress on morphine-induced behavioral
      sensitization in the rat.
AB  - The role of associative factors in the effect of 15 min/day of restraint stress
      on morphine-induced behavioral sensitization was examined. Male rats were
      initially given seven systemic (10 mg/kg, IP) or intraventral tegmental area
      (VTA, 5 micrograms/side) [corrected] injections of morphine, and were exposed to
      restraint, either just prior to drug injection (Paired-Stress) or 24 h after
      injection (Unpaired-Stress), or to no restraint (Control). In subsequent tests
      for behavioral sensitization to low doses of morphine (0.75 or 3.0 mg/kg, IP),
      animals in the Paired-Stress condition were more active than animals in the
      Unpaired-Stress or Control conditions. These results indicate that temporal and
      possibly associative factors may contribute to stress-induced changes in
      sensitization to the behavioral activating effects of opioids.

PMID- 7724694
TI  - The addictive role of nicotine in tobacco use.

PMID- 7724695
TI  - Nicotine intake in smokers increases following a single dose of haloperidol.
AB  - The effects of oral haloperidol on nicotine intake, subjective measures of
      craving and smoking satisfaction were compared with placebo in light-to-moderate
      smokers from a post-prandial cigarette and during the subsequent hour of
      unrestricted smoking. Subjects smoked significantly more, as measured by blood
      nicotine levels, when they had received haloperidol, although there was no
      difference between haloperidol and placebo on any subjective measures. These
      findings may be interpreted to reflect a compensatory increase in smoking in
      order to obtain the usual nicotine reward. Having achieved usual levels of
      reward, subjects did not experience a decrease in subjective measures of smoking
      satisfaction or an increase in nicotine craving.

PMID- 7724696
TI  - Social deprivation enhances the vulnerability of male Wistar rats to stressor-
      and amphetamine-induced behavioral sensitization.
AB  - The aim of the present study was to assess the influence of experiential factors
      on the vulnerability of rats to develop amphetamine (AMPH)- and stressor-induced
      behavioral sensitization. Young male Wistar rats with previous social experience
      were isolated from their peers for 2 weeks. 1) The effect of this short-lasting
      social deprivation were: a) a reduced tendency to explore a fearful environment;
      b) a prolonged exploratory activity in response to a novel but little fearful
      environment; and c) a dose-dependent increase in the psychomotor stimulation
      induced by systemic AMPH injection. 2) After repeated AMPH injections (injection
      every other day for 10 days), isolated rats exhibited behavioral sensitization at
      lower doses (0.5 and 0.75 mg/kg) than those required for group-housed rats (1
      mg/kg). 3) After being submitted to a repeated stressor (3, 7 or 14 footshock
      sessions, with 2 days between sessions), the isolated rats exhibited a greater
      increase in the behavioral responsivity to a subsequent AMPH challenge (1 mg/kg)
      than did the group-housed rats regardless of the number of stress sessions. In
      conclusion, these results suggest that experiential factors such as privation of
      contact with peers (social isolation) may make rats more vulnerable to the long
      term repercussions of chronic environmental and pharmacological challenges.

PMID- 7724698
TI  - Commentary on the nicotine is/is not addictive debate.

PMID- 7724697
TI  - The scientific case that nicotine is addictive.
AB  - Despite the wide-ranging and authoritative 1988 review by the US Surgeon General,
      views questioning the addictiveness of nicotine contine to be expressed in some
      quarters. This lack of complete consensus is not unexpected, since no universally
      agreed scientific definition of addiction exists. In this paper we briefly
      consider a number of lines of evidence from both the human and animal literature
      bearing on the addictiveness of nicotine. Patterns of use by smokers and the
      remarkable intractability of the smoking habit point to compulsive use as the
      norm. Studies in both animal and human subjects have shown that nicotine can
      function as reinforcer, albeit under a more limited range of conditions than with
      some other drugs of abuse. In drug discrimination paradigms there is some cross
      generalisation between nicotine on the one hand, and amphetamine and cocaine on
      the other. A well-defined nicotine withdrawal syndrome has been delineated which
      is alleviated by nicotine replacement. Nicotine replacement also enhances
      outcomes in smoking cessation, roughly doubling success rates. In total, the
      evidence clearly identifies nicotine as a powerful drug of addiction, comparable
      to heroin, cocaine and alcohol.

PMID- 7724699
TI  - Opioid operant self-administration, analgesia, stimulation and respiratory
      depression in mu-deficient mice.
AB  - It is commonly thought that mu-receptors play an important role in the
      reinforcing effects of opioids. In the present study, inbred strains widely
      divergent in CNS opiate receptor densities were used to investigate the influence
      of genetic variation in receptor concentration on opioid-reinforced behavior. In
      particular, the CXBK/ByJ mice were used as an investigative tool because of their
      significantly lower number of CNS mu opioid receptors. The behavioral
      pharmacology of opioids in the mu-deficient CXBK/ByJ mice was compared to other
      commonly used inbred mouse strains, C57BL/6J and BALB/cJ, and the opiate receptor
      rich CXBH/ByJ mice. Operant opioid reinforced behavior, opioid-induced locomotor
      stimulation, analgesia and respiratory depression were investigated in all four
      inbred strains. To assess the acquisition and maintenance of opioid reinforced
      behavior, oral self-administration of the potent benzimidazole opioid,
      etonitazene, was determined using an operant fixed-ratio schedule of
      reinforcement (FR 8). Acquisition of etonitazene-reinforced behavior was
      established in all four strains including the mu-deficient CXBK/ByJ mice.
      However, there were significant genetic differences in the amount of drug intake
      during the maintenance of opioid-reinforced behavior and extinction behavior
      following vehicle substitution. For example, drug intake was significantly
      greater in the BK versus BH mice during the maintenance phase and an extinction
      burst was seen in the BH but not the BK mice following vehicle substitution.
      Thus, mu-receptor density may not account for individual variability in the
      acquisition of opioid-reinforced behavior under these conditions. Sensitivity to
      etonitazene-induced respiratory depression, stimulation of locomotor activity and
      analgesia were unrelated to drug intake during self-administration sessions
      across these four inbred strains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724700
TI  - Conditioned ultrasonic distress vocalizations in adult male rats as a behavioural
      paradigm for screening anti-panic drugs.
AB  - Rats may produce ultrasonic vocalizations (USV) in threatening situations. USV of
      adult male rats in association with aversive stimulation was evaluated as a
      screening method for anxiolytic drugs. The triazolobenzodiazepine alprazolam, the
      5-HT uptake inhibitors fluvoxamine and clomipramine, the mixed 5-HT/NA uptake
      inhibitor imipramine, the full 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan,
      the partial 5-HT1A receptor agonists buspirone, ipsapirone and BMY 7378, the
      alpha 2-adrenoceptor agonist clonidine and the alpha 2-adrenoceptor antagonist
      yohimbine reduced conditioned USV. The classical benzodiazepines (BZD) diazepam
      and chlordiazepoxide were ineffective or had a very low potency to decrease USV.
      The partial BZD receptor agonists bretazenil, alpidem and zolpidem, the BZD
      receptor antagonist flumazenil, the NA uptake inhibitors desipramine and
      maprotiline, and the 5-HT3 receptor antagonist ondansetron had no effect on
      conditioned USV. The dopamine-D2 receptor antagonist haloperidol reduced USV at a
      very high dose. In separate experiments the effects of these drugs on locomotor
      activity were assessed. There was, however, no direct relationship between
      effects on motor behaviour and USV. In conclusion, the sensitivity of conditioned
      USV to 5-HT uptake inhibitors and alprazolam versus the insensitivity to
      classical benzodiazepines and NA uptake inhibitors provides a very interesting
      profile, which closely resembles the psychopharmacology of panic disorder. Also
      the face validity of conditioned USV towards situational panic attacks is high.
      We therefore propose conditioned USV in adult male rats as a novel behavioural
      paradigm to screen for anti-panic drugs.

PMID- 7724701
TI  - 8-OH-DPAT disruption of prepulse inhibition in rats: reversal with (+)WAY 100,135
      and localization of site of action.
AB  - Recent studies have implicated central serotonergic systems in the modulation of
      prepulse inhibition (PPI), an operational measure of sensorimotor gating, which
      has been used to identify gating deficits in psychiatric disorders, such as
      schizophrenia, Huntington's disease, and obsessive compulsive disorder. Both
      serotonin (5-HT) releasers and agonists at 5-HT1A, 5-HT1B, and 5-HT2 receptors
      reduce PPI in the rat. The present experiments demonstrate that the disruption of
      PPI in rats induced by the systemic administration of the 5-HT1A agonist, 8-OH
      DPAT (8-hydroxy-2(di-n-propylamino)tetralin; 0.2 mg/kg), can be attenuated by the
      novel, selective 5-HT1A antagonist (+)WAY 100,135, (20.0 mg/kg), N-tert-butyl-3
      (4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenyl-propa namide. Further experiments
      addressing the central site of action of 8-OH-DPAT revealed that the
      microinjection of 8-OH-DPAT (5.0 micrograms/0.5 microliter) into either the
      median raphe nucleus (MR) or dorsal raphe nucleus (DR) disrupts PPI. The
      reduction in PPI produced by intra-raphe microinjections of 8-OH-DPAT was
      prevented by a systemic injection of (+)WAY 100,135. These results support the
      hypothesis that somatodendritic 5-HT1A autoreceptors within the midbrain raphe
      subserve the PPI-disruptive effects of systemically administered 8-OH-DPAT. The
      decrement in PPI after intra-raphe infusions of a high dose of 8-OH-DPAT,
      however, was substantially less than the decrement in PPI after systemic
      administration of the drug. Hence, sites in addition to the somatodendritic
      autoreceptors may also play an important role in 8-OH-DPAT-induced disruption of
      PPI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724702
TI  - Development and reversal of sensitization to amphetamine-induced hypophagia: role
      of temporal, pharmacological, and behavioral variables.
AB  - This study shows that sensitization can develop to amphetamine-induced hypophagia
      and examines the stability of this effect following subsequent pharmacological
      and behavioral experience. Rats given 36 injections of either amphetamine (2.5
      mg/kg; Group A) or saline (Group S) at 3-day intervals developed sensitization of
      hypophagia, as assessed by a shift to the left in the dose-response (DR)
      function. Group A also displayed sensitization of stereotypy, whereas Group S
      showed little change except at the highest dose. Subgroups from each group were
      then given daily injections of amphetamine (2 mg/kg) either before or after
      access to milk for 4 weeks. Other subgroups were given injections of saline as a
      control. On a final DR determination, these control groups showed no further
      changes in milk intake. In contrast, groups given chronic injections of
      amphetamine after milk showed a loss of sensitization (DR3 = DR1), whereas groups
      given the drug before milk developed tolerance that was limited to the chronic
      dose. These results demonstrate that (1) sensitization of amphetamine-induced
      hypophagia and stereotypy can develop independently; (2) sensitization of
      hypophagia can be reversed, without inducing tolerance, by subsequent daily
      exposure to the drug; and (3) prior sensitization of hypophagia does not preclude
      the subsequent development of tolerance if the drug is later given in the context
      of feeding.

PMID- 7724703
TI  - Chromosomal mapping of loci influencing sensitivity to cocaine-induced seizures
      in BXD recombinant inbred strains of mice.
AB  - Among inbred mice, genetic factors mediate differences in sensitivity to the
      convulsant properties of cocaine; however, the gene(s) underlying cocaine's
      effects have not been identified. To help elucidate the gene(s) responsible for
      cocaine seizure susceptibility, we used recombinant inbred-quantitative trait
      loci (RI-QTL) analyses to identify chromosomal loci associated with cocaine
      induced seizures. RI-QTL analyses seek to identify associations between a
      quantitative measure of a particular phenotype and one or more previously mapped
      marker genes across a panel of RI strains. This report describes an RI-QTL
      analysis of cocaine seizure susceptibility among 26 BXD RI strains. These strains
      showed a skewed, bimodal range of seizure susceptibility which could be the
      result of one or more modifying genes acting in concert with a major gene to
      influence cocaine sensitivity. Correlating the percent seizures displayed by each
      strain following 60 mg/kg cocaine with chromosomal marker data for these strains
      revealed a number of significant correlations clustered in two regions on
      chromosomes 12 and 6. This is the first identification of putative chromosomal
      loci associated with a cocaine-related phenotype and should facilitate
      identification of the gene(s) underlying cocaine toxicity and other cocaine
      related phenotypes.

PMID- 7724704
TI  - In vivo pharmacological effects of dihydro-beta-erythroidine, a nicotinic
      antagonist, in mice.
AB  - The comparative in vivo pharmacology of mecamylamine and dihydro-beta
      erythroidine (DH beta E) in mice was studied. Modulation of the behavioral
      effects (antinociception, hypomotility, motor impairment and hypothermia) of
      nicotine in mice by DH beta E and mecamylamine were carried out. After SC
      administration, DH beta E and mecamylamine were nearly equipotent in blocking
      nicotine's effects except for antinociception, in which mecamylamine was clearly
      more potent. Intrathecal injection of DH beta E was also effective in blocking
      the antinociceptive effect of nicotine. In vivo interaction of DH beta E with
      calcium and calcium channels, involved in the central actions of nicotine, showed
      that intrathecal administration of DH beta E failed to reduce the antinociception
      induced by diverse drugs which increase intracellular calcium such as
      thapsigargin, (+/-)-BAYK 8644 and calcium, indicating that this antagonist does
      not affect calcium-dependent mechanisms involved in antinociception. On the other
      hand, mecamylamine blocked the antinociceptive effect of the calcium modulatory
      drugs, suggesting that it may be acting on calcium-dependent mechanisms involved
      in the intracellular signaling process. We conclude that DH beta E, a nicotinic
      neuromuscular antagonist, is able to block some of the central actions of
      nicotine after systemic and intrathecal administration. The mechanism of blockade
      is different from that of mecamylamine, a classical ganglionic antagonist, and
      may involve a direct action of DH beta E on nicotine receptor.

PMID- 7724705
TI  - Neuroleptic-induced vacuous chewing movements in rodents: incidence and effects
      of long-term increases in haloperidol dose.
AB  - Rats treated chronically with neuroleptics develop vacuous chewing movements
      (VCMs), similar in some respects to tardive dyskinesia (TD) in man. The VCM
      syndrome was used as a model of TD to examine the ability of increased
      neuroleptic doses to produce long-term suppression of dyskinetic movements. The
      incidence and persistence of the VCM syndrome in individual rats were also
      assessed to look for affected and unaffected subgroups. Rats were initially
      treated for 15 weeks and haloperidol decanoate. For the next 21 weeks, half the
      group received a 50-150% increase in dose while the other half continued to
      receive the same dose. Animals were also followed during a 28-week withdrawal
      period. Total VCM ratings showed a skewed distribution, with some rats exhibiting
      few movements while others developed marked and persistent movements. Increasing
      doses did not suppress VCMs, nor did they exacerbate movements during the
      withdrawal period. To the extent that the VCM syndrome models TD, the absence of
      long-term suppression of the VCM syndrome suggests that, at this dosage range,
      increasing depot neuroleptic doses may not be a useful long-term strategy for TD
      suppression.

PMID- 7724708
TI  - The clinical and financial burden of mood disorders. Cost and outcome.
AB  - Depressive disorders are a chronic, recurrent, and severe burden to both patients
      and their families. Depressive disorders represent a major national public health
      problem, ranking within the top 10 most costly diseases in the United States. In
      1990, depressive disorders afflicted at least 11 million Americans and cost the
      U.S. economy an estimated $44 billion. In addition, affective disorders are
      associated with increased accident rates, increased rates of substance abuse
      (especially alcoholism), increased medical hospitalization, and an increase in
      somatic illnesses and outpatient medical utilization. Despite their ranking as a
      major health problem, depressive disorders are often underdiagnosed and
      undertreated. Brief treatment strategies that focus only on acute episodes are
      often ineffective and result in chronic impairment, impairing performance at work
      and socially. Inadequate treatment increases costs, suffering, and lost
      productivity. Recent data suggest that effective treatment of depression requires
      long-term, skillful follow-up and active pharmacotherapy.

PMID- 7724706
TI  - Analysis of the effects of intra-accumbens SKF-38393 and LY-171555 upon the
      behavioural satiety sequence.
AB  - The outcome of intra-accumbens infusions of the dopamine D1 receptor family
      agonist SKF-38393 and the D2 receptor family agonist LY-171555 upon measures
      taken during the behavioural satiety sequence was assessed (0.01 micrograms, 0.1
      micrograms, 1.0 micrograms in each case). Each drug was infused either
      separately, or together as a co-infusion in order to examine the functional
      relationship between these dopamine receptor subtypes within the nucleus
      accumbens. Measures of feeding did not change following infusions of SKF-38393 or
      LY-171555, whether infused separately or together. However, following separate
      infusion of the lowest dose tested of each drug (0.01 micrograms), the onset of
      resting was advanced. Moderate to high doses of SKF-38393 and LY-171555 (0.1
      micrograms, 1.0 micrograms) infused separately resulted in a marked increase in
      activity at the expense of resting. Co-infusion of 0.01 micrograms of each drug
      also resulted in a dramatic increase in activity. Thus, measures of feeding
      behaviour were unchanged following excitation of D1 and D2 dopamine receptor
      families within the nucleus accumbens. In marked contrast, locomotor behaviour
      appeared to be under the potent synergistic control of these receptor families.

PMID- 7724709
TI  - Expanding psychopharmacologic treatment options for the depressed medical
      patient.
AB  - Psychopharmacologic treatment of depression in medically ill patients is greatly
      enhanced by the availability of new antidepressant medications that have low or
      no anticholinergic, anti-alpha-adrenergic, antihistaminic, and quinidine-like
      properties. This article discusses the important pharmacodynamic and
      pharmacokinetic properties of the selective serotonin reuptake inhibitors
      (fluoxetine, paroxetine, and sertraline), bupropion, venlafaxine, and nefazodone-
      with an emphasis on their side effects relevant to medical patients as well as
      important drug interactions. In addition, the safety of these newer medications
      is compared with that of tricyclics; the role for continued tricyclic use in the
      medical-psychiatric population is examined; the use of electroconvulsive therapy
      in medically ill patients who are refractory to antidepressants is also briefly
      discussed.

PMID- 7724707
TI  - Effects of indorenate on food intake: a comparison with fenfluramine and
      amphetamine.
AB  - Indorenate (TR3369, 5-methoxytryptamine b-methylcarboxylate HCl) is a 5-HT1-like
      receptor agonist with hypotensive activity. Here, we describe that indorenate
      also decreases food intake (ED50 26.1 mg/kg) without an appreciable effect in
      water intake (the estimated ED50 for water was 589.8 mg/kg). The anorectic
      activity of indorenate was compared to the effects of amphetamine and other
      serotonin agonists; the effect of indorenate was smaller than those of the other
      compounds; however, the effect of indorenate was specific to food, whereas all
      the other drugs also produced significant decrements in water intake. The
      serotonin antagonists cinanserin, cyproheptadine, methergoline and methysergide
      effectively prevented the decrease in food intake produced by indorenate and
      fenfluramine. Haloperidol, a dopaminergic antagonist, was ineffective in
      preventing the effect of indorenate although it prevented the anorectic effect of
      amphetamine. The present results suggest the participation of serotoninergic, but
      not dopaminergic mechanisms, in the decrease in food intake produced by
      indorenate.

PMID- 7724710
TI  - Depressive disorders in the medically ill. An overview.
AB  - Depressive disorders are far more serious than most people realize, and
      depressive disorders are disabling affected persons progressively earlier in
      life. Heavy utilization of medical services, extensive disability and morbidity,
      and high suicide risk exact a staggering economic toll in the United States
      annually. Depressive illness is, like pneumonia and septic shock, a dread
      complication of major medical illness, and depressive illness appears more
      frequently as the medical illness worsens; diseases affecting the brain may have
      the highest rates of depressive symptoms. Correctly diagnosing a depressive
      disorder in a medically ill patient is a clinical challenge that requires
      systematic, persistent clinical scrutiny. Compassion demands that depressive
      disorders, when diagnosed, be treated aggressively.

PMID- 7724711
TI  - Intractable sneezing as a conversion symptom.
AB  - A literature review of reported cases of intractable sneezing reveals that
      intractable sneezing typically occurs in children or adolescents and is a
      manifestation of conversion disorder. Analysis of these cases demonstrates a
      number of features that are helpful in differentiating psychogenic from organic
      sneezing. Also discussed are aspects of patient management once a diagnosis of
      conversion disorder is established.

PMID- 7724712
TI  - Composition and funding. Consultation-liaison psychiatry services.
AB  - All of the programs in the Academy of Psychosomatic Medicine directory of U.S.
      consultation-liaison (C-L) fellowship training (N = 49) responded to a
      questionnaire to document composition and funding of their staff. The mean annual
      budget was $324,664 (range $40,000-$550,000), with a mean of 2.4 full-time
      equivalents and 1.6 fellowship training positions. A significant patient cohort
      and C-L staff and fellows exist in these programs to launch important hypothesis
      generation studies.

PMID- 7724713
TI  - Health care utilization of somatizing patients in a pulmonary subspecialty
      clinic.
AB  - Somatizing patients present with medically unexplained physical complaints,
      repeat clinic visits, and a history of prior extensive testing. The authors
      reviewed 1,908 pulmonary consultation reports for 1990-1991 for evidence of
      somatization, yielding a group of 41 (2%) patients for study. Billing records
      were obtained and were compared to asthmatic patients and those in a health
      maintenance organization (HMO). Health care costs for the somatizing patients
      were significantly higher than the average cost for HMO patients and comparable
      to the health costs for patients with asthma. Half of the somatizing patients had
      psychological problems indicated in their medical records, but few received
      psychiatric referral or treatment. Management of the somatizing patient within
      the specialty clinic and on-site psychiatric treatment are suggested as ways to
      decrease unnecessary health care utilization.

PMID- 7724714
TI  - Major depression in primary care practice. Clinical characteristics and treatment
      implications.
AB  - Major depression is thought to be underdiagnosed and undertreated in primary
      medical care facilities. The authors conducted a clinical trial that included a
      three-phase assessment so only ambulatory medical patients judged eligible for
      treatment of this disorder in medical settings were recruited. In addition to
      administering the Center for Epidemiologic Studies-Depression scale and the
      Diagnostic Interview Schedule's (DIS) Depression section, the psychiatrists
      evaluated the DIS-positive patients. This third assessment determined that
      clinical characteristics of DIS-positive patients were such that 70% of the
      patients could be treated for major depression in a primary care setting, 13%
      should probably be referred to a mental health facility, and 17% were
      experiencing conditions other than major depression.

PMID- 7724715
TI  - Course and outcome of conversion and somatization disorders. A four-year follow
      up.
AB  - Although the two disease concepts have very different histories, many previous
      studies have mixed conversion disorder and somatization disorder and none has
      made direct comparison between them. The authors applied DSM-III criteria to
      inpatient and outpatient medical records and attempted to follow 98 patients who
      met criteria for somatization disorder or conversion disorder. Five of these
      patients died 4 years later and, of those who survived, 70 (75.3%) were given
      follow-up interviews by a rater blind to baseline diagnosis. The 32 patients with
      a baseline diagnosis of conversion disorder were significantly less likely than
      the 38 patients with somatization disorder to be given the same diagnosis at
      follow-up. Six of the conversion disorder patients were given follow-up diagnoses
      of somatization disorder and, in four other cases, subsequent developments
      revealed medical explanations for the presenting complaint. Of the two baseline
      diagnoses, somatization disorder predicted substantially more impairment in a
      variety of domains.

PMID- 7724716
TI  - Hypomania precipitated by psychostimulant use in depressed medically ill
      patients.

PMID- 7724717
TI  - Obsessive-compulsive disorder in HIV disease. Response to fluoxetine.

PMID- 7724718
TI  - Neuropathogenesis of delirium.

PMID- 7724719
TI  - Neuropathogenesis of delirium.

PMID- 7724720
TI  - Serotonin syndrome produced by paroxetine and low-dose trazodone.

PMID- 7724721
TI  - Academic consultation-liaison services. The problems and the promise.

PMID- 7724722
TI  - Recent changes in consultation-liaison psychiatry. A blueprint for the future.
AB  - To better understand the changes in the past 5 years on consultation-liaison (C
      L) services in the United States, 119 university programs were surveyed. The
      return response was 64%. Of the 76 respondents, 32% had decreased funding, 54% no
      changes or stable finding, and 14% improved funding. Nonetheless, 57% of the
      programs reported funding difficulties as a major problem. Understaffing was
      reported by 51% of the programs. Liaison activities have ceased or are reduced in
      70% of the programs; 15% reported an increase in liaison, particularly for
      transplantation. C-L services have been affected by illness acuity (68%), shorter
      hospital stays (79%), and older populations (54%). The diagnostic mix shows
      increases in HIV-related disorders, drug abuse, and delirium. The discussion
      includes recommendations for C-L services given these findings.

PMID- 7724723
TI  - A study in Renaissance psychotropic plant ointments.
AB  - Various historical sources from the Renaissance--including transcripts of trials
      for witchcraft, writings on demonology and textbooks of pharmaceutical botany-
      describe vegetal ointments prepared by women accused of witchcraft and endowed
      with marked psychoactive properties. Here, we examine the botanical composition
      and the possible pharmacological actions of these ointments. The results of our
      study suggest that recipes for narcotic and mind-altering salves were known to
      Renaissance folk healers, and were in part distinct from homologous preparations
      of educated medicine. In addition, our study reveals an unexpected connection of
      these vegetal psychotropes with archaic chtonic beliefs, confirming the tight
      association between rituals and cults entered on the Underworld and the image of
      the Medieval witch.

PMID- 7724724
TI  - [AIDS in Naples in 1800. 12 cases of Kaposi sarcoma described by Tommaso de
      Amicis].
AB  - In 1882, Tommaso de Amicis, dermatologist and venereologist at the University of
      Naples, Italy, published a description of twelve cases of Kaposi's sarcoma. This
      article is the second report about the above-mentioned disease after the first
      description of five cases by Moritz Kaposi ten years earlier. The publication by
      De Amicis was organized as a collection of case reports followed by a section
      containing general considerations about the etiopathogenesis, pathology,
      diagnosis and therapy of Kaposi's sarcoma. Ten cases are typical of the so-called
      'classic' form of the disease, that has a peculiar indolent chronic course, while
      two out of the twelve cases strongly resemble the clinical form of Kaposi's
      sarcoma currently recognized as that associated with the acquired
      immunodeficiency syndrome (AIDS). The nature of Kaposi's sarcoma is still being
      debated, but current evidence suggests that it is a viral-associated, if not
      viral-induced, tumor and its relationship with AIDS is that of an opportunistic
      disease. Thus, the presence of the clinical form of AIDS-related Kaposi's sarcoma
      can be used as a marker of the presence of sporadic cases of AIDS much earlier
      than its pandemic diffusion.

PMID- 7724725
TI  - [History of virology, viral diseases, and virologists].

PMID- 7724727
TI  - Role of scavenger-derived radicals in the induction of double-strand and single
      strand breaks in irradiated DNA.
AB  - Studies of intact cells have generally shown a substantial enhancement by oxygen
      of radiation-induced cell killing or DNA breakage, with an oxygen enhancement
      ratio (OER) of 2.5-3. Analogous studies of radiation damage to purified DNA in
      aqueous solution, performed at much lower .OH scavenging efficiencies, have
      usually shown little or no damage enhancement by oxygen (OER approximately 1)
      unless reduced thiol compounds were also present during irradiation. Milligan and
      Ward (Radiat. Res. 137, 295-299, 1994) recently observed an excess of DNA single
      strand breaks (SSBs) in nitrogen compared to air (OER < 1) for SV40 DNA
      irradiated in the presence of high concentrations of DMSO, and they presented
      evidence that this excess resulted from secondary DMSO radicals. We have here
      investigated the role of secondary radicals from glycerol, another non-thiol .OH
      scavenger, in the induction of DNA double-strand breaks (DSBs), lesions which are
      critical to cell death. Superhelical SV40 DNA, 25 micrograms/ml, was irradiated
      in air or nitrogen in the presence of 0-2500 mM glycerol. Resultant DSBs and SSBs
      were measured simultaneously by computer analysis of digital video images of
      ethidium bromide-stained gels. The OERs for DSBs and SSBs decreased from 1.3 at
      the lowest glycerol concentration to 0.65 and 0.45, respectively, at the highest
      concentration, consistent with an important role for anoxic secondary radicals in
      the presence of high glycerol concentrations. The dose-response curves for SSBs
      due to glycerol radicals are predominantly "one-hit" over the entire glycerol
      concentration range where they were observable (> or = 75 mM). The dose-response
      curves for DSBs due to glycerol radicals are predominantly one-hit at high
      glycerol concentrations (> or = 750 mM). Analysis of the data suggests that the
      dominant mechanism for the formation of glycerol radical-induced one-hit DSBs at
      lower glycerol concentrations (< or = 750 mM) involves a single glycerol radical
      resulting in two nearby SSBs on opposite DNA strands, analogous to the mechanism
      proposed by Siddiqi and Bothe (Radiat. Res. 112, 449-463, 1987) for the induction
      of a DSB by a single OH radical. Our data for the highest concentration (2500 mM)
      imply that it is now important to take into account a second mechanism.

PMID- 7724726
TI  - Effects of low doses and low dose rates of external ionizing radiation: cancer
      mortality among nuclear industry workers in three countries.
AB  - Studies of the mortality among nuclear industry workforces have been carried out,
      and nationally combined analyses performed, in the U.S., the UK and Canada. This
      paper presents the results of internationally combined analyses of mortality data
      on 95,673 workers (85.4% men) monitored for external exposure to ionizing
      radiation and employed for 6 months or longer in the nuclear industry of one of
      the three countries. These analyses were undertaken to obtain a more precise
      direct assessment of the carcinogenic effects of protracted low-level exposure to
      external, predominantly gamma, radiation. The combination of the data from the
      various studies increases the power to study associations between radiation and
      specific cancers. The combined analyses covered a total of 2,124,526 person-years
      (PY) at risk and 15,825 deaths, 3,976 of which were due to cancer. There was no
      evidence of an association between radiation dose and mortality from all causes
      or from all cancers. Mortality from leukemia, excluding chronic lymphocytic
      leukemia (CLL)--the cause of death most strongly and consistently related to
      radiation dose in studies of atomic bomb survivors and other populations exposed
      at high dose rates--was significantly associated with cumulative external
      radiation dose (one-sided P value = 0.046; 119 deaths). Among the 31 other
      specific types of cancer studied, a significant association was observed only for
      multiple myeloma (one-sided P value = 0.037; 44 deaths), and this was
      attributable primarily to the associations reported previously between this
      disease and radiation dose in the Hanford (U.S.) and Sellafield (UK) cohorts. The
      excess relative risk (ERR) estimates for all cancers excluding leukemia, and
      leukemia excluding CLL, the two main groupings of causes of death for which risk
      estimates have been derived from studies of atomic bomb survivors, were -0.07 per
      Sv [90% confidence interval (CI): -0.4, 0.3] and 2.18 per Sv (90% CI: 0.1, 5.7),
      respectively. These values correspond to a relative risk of 0.99 for all cancers
      excluding leukemia and 1.22 for leukemia excluding CLL for a cumulative
      protracted dose of 100 mSv compared to 0 mSv. These estimates, which did not
      differ significantly across cohorts or between men and women, are the most
      comprehensive and precise direct estimates of cancer risk associated with low
      dose protracted exposures obtained to date. Although they are lower than the
      linear estimates obtained from studies of atomic bomb survivors, they are
      compatible with a range of possibilities, from a reduction of risk at low doses,
      to risks twice those on which current radiation protection recommendations are
      based.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7724728
TI  - Radiation-induced DNA double-strand breaks produced in histone-depleted tumor
      cell nuclei measured using the neutral comet assay.
AB  - Removal of histones and other nuclear proteins greatly enhances the sensitivity
      of mammalian cells to DNA damage by ionizing radiation. We examined the
      possibility that the ease of dissociation of histones, or the association of
      other nuclear proteins with DNA, may differ between radioresistant and sensitive
      human tumor cells. Cells embedded in agarose were exposed to increasing salt
      concentrations prior to irradiation and examination using a microscopic gel
      electrophoresis method, the neutral comet assay. Induction of double-strand
      breaks increased by a factor of about 20 when cells of four human tumor cell
      lines, HT144 melanoma, HT29 adenocarcinoma, DU145 prostate carcinoma and U87
      glioma, were exposed to 2 M NaCl prior to irradiation. Subtle differences in
      sensitivity to induction of double-strand breaks by radiation between cells of
      the four cell lines were also observed after extraction with 0.7-1.1 M NaCl;
      however, no correlation with radiosensitivity was apparent. While a significant
      number of histone and non-histone proteins are present after extraction with 1.2
      M NaCl, these proteins apparently have only a minor influence on
      radiosensitivity. However, if they are allowed to remain with DNA during
      electrophoresis, about 15 times more strand breaks are required to produce a
      similar amount of DNA migration in both DU145 and HT144 cells. These results
      suggest that the association between proteins and DNA within the nucleus, as
      probed by extraction with sodium chloride, does not help to explain differences
      in intrinsic radiosensitivity among cells of these diverse tumor cell lines.

PMID- 7724729
TI  - Linear induction of DNA double-strand breakage with X-ray dose, as determined
      from DNA fragment size distribution.
AB  - Pulsed-field gel electrophoresis has been applied to separate DNA from mouse
      L1210 cells exposed to X-ray doses of 1 to 50 Gy. Simultaneous separation of
      marker chromosomes in the range 0.1 to 12.6 Mbp allowed calculation of the size
      distribution of the radiation-induced fragments. The distribution was consistent
      with a random induction of double-strand breaks (DSBs). A theoretical
      relationship between the size distribution of such fragments and the average
      number of induced breaks was used to calculate the yield and dose response. The
      DNA distribution was determined by both radiolabeling and fluorescence staining.
      Two independent methods were used to evaluate the radiation-induced yield of
      DSBs, both assuming that all DNA is broken at random. In the first method we
      compared the theoretical and experimental fraction of DNA that is below a given
      size limit. By this method we estimated the yield to be 0.006-0.007 DSB/Gy per
      million base pairs using the radiolabel and 0.004-0.008 DSB/Gy per million base
      pairs by fluorescence staining. The dose response was linear in both cases. In
      the second method we looked only at the size distribution in the resolving part
      of the gel and compared it to the theoretical distribution. By this method a
      value of approximately 0.012 DSB/Gy/Mbp was found, using fluorescence as a
      measure of DNA distribution. In a normal diploid mammalian genome of size 6000
      Mbp, this is equivalent to a yield of 25-50 DSBs/Gy or 70 DSBs/Gy, respectively.
      The second approach, which looks only at the smaller fragments, may overestimate
      the yield, while the first approach suffers from uncertainties about the fraction
      of DNA irreversibly trapped in the well. The assay has the capacity to detect a
      dose of less than 1 Gy.

PMID- 7724730
TI  - Radiation-induced DNA damage in tumors and normal tissues. III. Oxygen dependence
      of the formation of strand breaks and DNA-protein crosslinks.
AB  - Results from several laboratories, including ours, have suggested that
      measurements of radiation-induced DNA strand breaks and DNA-protein crosslinks
      (DPCs) may be used to estimate the hypoxic fraction or fractional hypoxic volume
      of tumors and normal tissues. This suggestion has been predicted on both
      published and unpublished information that (1) the oxygen dependence of the
      formation of strand breaks in irradiated mammalian cells is similar to the oxygen
      dependence of radiation-induced cell killing, and (2) the oxygen dependence of
      the formation of DPCs in irradiated mammalian cells is the mirror image of the
      oxygen dependence of radiation-induced cell killing. However, the published
      studies that attempted to determine the relationship between the oxygen
      dependence of the formation of strand breaks and the radiation sensitivity of
      mammalian cells were not performed at 37 degrees C, the exact oxygen
      concentrations were not always known, and the results were conflicting. In
      addition, most of the data on the oxygen dependence of the formation of DPCs are
      unpublished. Consequently, we have undertaken a comprehensive investigation of
      one cell line, 9L/Ro rat brain tumor cells, to determine if the shape of the
      oxygen dependence curve and the Km value for radiation-induced strand breaks and
      DPCs were similar when 9L cells were irradiated under both ideal gas-liquid
      equilibrium conditions at 4 degrees C and nonideal gas-liquid equilibrium
      conditions at 37 degrees C. At 4 degrees C under ideal gas-liquid equilibrium
      conditions, the Km for the formation of strand breaks was approximately 0.0045
      mM, and the Km for radiation sensitivity was approximately 0.005 mM. A similar
      comparison for the formation of DPCs at 4 degrees C could not be made, because
      the efficiency of the formation of DPCs was much lower at 4 degrees C than at 37
      degrees C. At 37 degrees C under nonideal gas-liquid equilibrium conditions, the
      apparent Km for the formation of strand breaks and radiation sensitivity was
      approximately 0.032 mM, and the Km for the formation of DPCs was approximately
      0.02 mM. The data for strand breaks are in agreement with the published data of
      Chapman et al. (Int. J. Radiat. Biol. 26, 383-389, 1974), and the data for DPCs
      are in agreement with the unpublished data of Meyn (personal communication).
      These results support the suggestion that measurements of radiation-induced
      strand breaks and/or DPCs may be used to detect hypoxic cells and estimate the
      hypoxic fraction or fractional hypoxic volume of tumors and normal tissues.

PMID- 7724731
TI  - Regulation of DNA replication in irradiated cells by trans-acting factors.
AB  - We compared DNA replication activity in cytoplasmic extracts prepared from
      irradiated and nonirradiated HeLa cells using a simian virus 40 (SV40)-based in
      vitro replication assay. The assay measures semi-conservative DNA replication in
      a plasmid carrying the SV40 origin of replication and requires SV40 T antigen as
      the sole noncellular protein. The plasmid DNA used in the replication reaction is
      never exposed to radiation. We find that replication of plasmid DNA is
      significantly reduced when cytoplasmic extracts from irradiated cells are used.
      Since plasmid replication proceeds to completion in extracts from irradiated
      cells, the observed reduction in the over-all replication activity is probably
      due to a reduction in the efficiency of initiation events. The degree of
      inhibition of DNA replication after exposure to 10, 30 and 50 Gy X rays as
      measured in vitro using this assay is similar to that measured in intact cells
      immediately before processing for extract preparation. These observations are
      compatible with the induction or activation by ionizing radiation of a factor(s)
      that inhibits in trans DNA replication. The results contribute to our
      understanding of the mechanism(s) developed by the cells to regulate DNA
      replication when exposed to clastogenic agents. Such processes may be of
      significance in the restoration of DNA integrity, and may define yet another
      checkpoint operating during S at the level of clusters of replicons.

PMID- 7724732
TI  - Cultured cells from a severe combined immunodeficient mouse have a slower than
      normal rate of repair of potentially lethal damage sensitive to hypertonic
      treatment.
AB  - The effects of hypertonic 0.5 M NaCl treatment after irradiation on the repair of
      DNA damage were examined in fibroblasts of the severe combined immunodeficient
      (scid) mouse. These cells are hypersensitive to ionizing radiation because of a
      deficiency in the repair of double-strand breaks. Hypertonic treatment caused
      radiosensitization due to a fixation of potentially lethal damage (PLD) in scid
      cells, demonstrating that scid cells normally repair PLD. To assess the kinetics
      of the repair of PLD, hypertonic treatment was delayed for various times after
      irradiation. Potentially lethal damage was repaired during these times in
      isotonic medium at 37 degrees C. It was found that the rate of repair of PLD was
      much slower in scid cells than in BALB/c 3T3 cells, which have a "wild-type"
      level of radiosensitivity. This fact indicates that the scid mutation affects the
      type of repair of PLD that is sensitive to 0.5 M NaCl treatment. In scid hybrid
      cells containing fragments of human chromosome 8, which complements the
      radiosensitivity of the scid cells, the rate of repair was restored to a normal
      level. An enzyme encoded by a gene on chromosome 8 may also be connected with PLD
      which is sensitive to hypertonic treatment.

PMID- 7724733
TI  - Primary explants of human uroepithelium show an unusual response to low-dose
      irradiation with cobalt-60 gamma rays.
AB  - Recent results using very low doses of radiation have suggested that there is a
      hypersensitive region where cultures show an enhanced level of cell killing
      leading to a non-monotonic survival curve. This effect has been observed at doses
      below 2 Gy in mammalian systems and at much higher doses in insect cells. In this
      paper we report observation of the effect in primary human uroepithelial cell
      cultures. The effect was measured using a postirradiation proliferation assay
      where irradiated explants of standard size were allowed to proliferate for 14
      days after exposure to 60Co gamma irradiation. By 14 days the majority of
      cultures derived from explants irradiated with 2-5 Gy showed little evidence of
      growth inhibition and cell numbers approached or even exceeded those obtained in
      the controls. There was, however, a significant reduction in cell number and
      growth rate in all cultures exposed to doses lower than 1 Gy. Oncoprotein (p53, c
      myc, bcl-2, p21 ras) and EGFR expression were also measured in these cultures and
      were significantly increased. Morphological evidence of apoptosis was present in
      all irradiated cultures at 4 h after exposure, but this persisted for longer
      periods in cultures exposed to low doses.

PMID- 7724734
TI  - Heterogeneity in c-jun gene expression in normal and malignant cells exposed to
      either ionizing radiation or hydrogen peroxide.
AB  - We investigated the role of reactive oxygen intermediates and protein kinase C in
      the induction of expression of the c-jun gene in human ML-2 leukemic cells and
      normal human DET-551 fibroblasts by comparing the effects of exposure to either
      ionizing radiation or H2O2 in the presence or absence of appropriate inhibitors.
      In these cell types, the radiation- and H2O2-mediated increase in c-jun mRNA
      levels could be prevented by pretreatment of the cells with N-acetylcysteine, an
      antioxidant, or H7, an inhibitor of protein kinase C and protein kinase A, but
      not by HA1004, a specific inhibitor of protein kinase A and G. These results
      suggest a role for protein kinase C and reactive oxygen intermediates in the
      induction of c-jun gene expression in both normal and tumor cells. We also
      investigated potential differences in c-jun gene expression induced by radiation
      or H2O2 in normal and tumor cells by examining steady-state c-jun mRNA levels in
      a number of human fibroblast, leukemia, melanoma, sarcoma and carcinoma cell
      types. We observed heterogeneity in the steady-state level of c-jun mRNA in both
      the untreated normal and tumor cells and in such cells exposed to ionizing
      radiation or to H2O2. Exposure to radiation produced a varied response which
      ranged from little or no induction to an increase in the steady-state level of
      the c-jun mRNA of more than two orders of magnitude. Exposure to H2O2 gave a
      pattern similar to that of ionizing radiation. The basis for the differential
      induction in response to these agents may be attributable to either cell lineage
      or genetic heterogeneity or a combination of these two parameters.

PMID- 7724736
TI  - The relative significance of repopulation and hypoxic clonogens in the
      fractionated radiotherapy of a mouse tumor.
AB  - The aim of this study was to analyze the significance of the repopulation of
      tumor cell clonogens, reoxygenation and hypoxic cells for the outcome of
      fractionated radiotherapy. Our previous fractionation study using a murine tumor
      was used for the analysis (Nishimura and Urano, Int. J. Radiat. Oncol. Biol.
      Phys. 29, 141-148, 1994). In the previous study, single cell suspensions were
      prepared from the early-generation isotransplants of a spontaneous fibrosarcoma,
      FSa-II, in a C3Hf/Sed mouse and transplanted into the foot of C3Hf/Sed mice.
      Fractionation schedules consisted of equal graded daily doses (1-20 fractions)
      given in air or under hypoxic conditions with 137Cs. Treatment was initiated when
      tumors reached an average diameter of 4 mm. A twice-a-day (b.i.d.) irradiation
      was tested for 20 doses. Tumor control was the end point, and the TCD50 (50%
      tumor control dose) was obtained. The surviving fractions resulting from these
      TCD50 doses were calculated using the alpha and beta values for the FSa-II cells,
      assuming that these values were constant throughout the fractionation period.
      These surviving fractions were used to calculate the clonogen repopulation and
      the reoxygenation of the hypoxic cells. Tumor clonogens repopulated rapidly and
      the hypoxic cells appeared to reoxygenate substantially during 10-20 doses. In
      the fractionation regimens consisting of more than 5 doses, the repopulation
      became significant. This rapid repopulation was reflected as a small alpha/beta
      ratio on the Fe plot. During 20 daily doses given under hypoxic conditions,
      clonogens (including both oxygenated and hypoxic) repopulated by a factor of 1.9
      x 10(6). The hypoxic clonogens (based on the TCD50 after doses in air)
      repopulated to a much lesser extent than did the total clonogens. Reoxygenation
      was not substantial up to 5 daily doses but appeared to become significant during
      10 to 20 doses. The magnitude of reoxygenation appeared to be substantially
      greater during 20 daily doses than during 20 b.i.d. doses. The significance of
      the hypoxic cells appeared to be less with increasing fractionation for the tumor
      control, but still remained critical in 20 daily doses. This study also suggested
      that the inhibition of clonogen repopulation could improve the outcome of
      radiotherapy, but this inhibition should be accompanied by further reoxygenation
      as long as hypoxic clonogens remain critical for the tumor control.

PMID- 7724735
TI  - Differences in correlation of mRNA gene expression in mice sensitive and
      resistant to radiation-induced pulmonary fibrosis.
AB  - Fibrosis, characterized by the accumulation of collagen, is a late result of
      thoracic irradiation. The purpose of this study was to determine if extracellular
      matrix protein and transforming growth factor beta mRNA expression are altered
      late in the course of pulmonary fibrosis after irradiation, and then to determine
      if these changes differ between two strains of mice which vary in their
      sensitivity to radiation. Radiation-sensitive (C57BL/6) and radiation-resistant
      (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax.
      Total lung RNA was prepared and immobilized by Northern and slot blotting and
      hybridized with radiolabeled cDNA probes for collagens I, III and IV,
      fibronectin, and transforming growth factor beta 1 and beta 3. Autoradiographic
      data were quantified by video densitometry and results normalized to a control
      probe encoding for glyceraldehyde-3-phosphate dehydrogenase. Alterations in mRNA
      abundance were observed in the sensitive mice at all times, while levels in the
      resistant mice were unaffected until 26 weeks after irradiation. The relationship
      between extracellular matrix protein per se and increased mRNA abundance suggests
      that late matrix protein accumulation may be a function of gene expression.
      Differences in levels of transforming growth factor beta mRNA may lead to strain
      dependent variation in fibrotic response and may also contribute to the radiation
      induced component of pulmonary fibrosis.

PMID- 7724738
TI  - A transient mathematical model of oxygen depletion during photodynamic therapy.
AB  - A transient one-dimensional mathematical model is presented to help visualize the
      qualitative and quantitative effects on inter-capillary tissue undergoing
      photodynamic therapy (PDT). The model is solved by a Crank-Nicholson finite
      difference formulation to provide time-dependent concentrations of the Type II
      mechanism's photo-oxidation species in the tissue surrounding a capillary. The
      time-dependent solution allows educated decisions to be made as to the optimum
      timing of light fractionation (on/off) cycles. Qualitative and quantitative
      optimization of the PDT process is considered along with a case study of data in
      the literature, the main goal being to provide optimized light therapy regimens
      for eventual clinical use.

PMID- 7724739
TI  - Kinetics and products of OH radical addition to baicalin.
AB  - The reaction of OH radicals with baicalin was studied by pulse and gamma
      radiolysis in N2O-saturated aqueous solutions. The addition of an OH radical to
      baicalin produced an intermediate species that shows a maximum UV absorbance band
      at 420 nm and decays with a unimolecular rate constant of 1.25 x 10(4) s-1 and a
      bimolecular rate constant of 6.1 x 10(8) mol-1 dm3 s-1. Four major final products
      were obtained by gamma irradiation, and their structures were identified. Two of
      them (P1 and P2) are suggested to originate from the unimolecular reaction and
      the other two (P3 and P4) from the bimolecular reaction of the radicals.

PMID- 7724737
TI  - Radiation inhibition of intimal hyperplasia after arterial injury.
AB  - To demonstrate the effect of gamma radiation on proliferating smooth muscle cells
      in vivo, a standardized bilateral carotid balloon catheter arterial injury was
      produced in 45 rats and doses from 0-20 Gy were delivered to the right carotid
      artery at 24 h after injury. At 20 days after injury, cross-sectional area of
      intima was determined from axial histological sections. Compared to
      contralateral, nonirradiated balloon-injured arteries, radiation produced a
      significant dose-dependent reduction in intimal cross-sectional area, with a 50%
      decrease at 5-7.5 Gy. To determine the effect of timing of irradiation on intimal
      hyperplasia, 30 rats with bilateral carotid injury received unilateral cervical
      irradiation at doses of 1, 5 or 10 Gy administered at either 1, 3 or 5 days after
      injury. The radiation dose (P = 0.0002), timing of irradiation (P = 0.003) and an
      interaction between timing and dose (P = 0.0278) were significantly associated
      with reduction in neointimal cross-sectional area. To determine the effects of
      radiation on intimal hyperplasia at later intervals, rats irradiated with 15 (n =
      5) or 20 Gy (n = 5) were euthanized at 3 months after injury. A significant
      persistent reduction in intimal cross-sectional area for irradiated arteries at 3
      months was associated with minimal apparent radiation effects upon adjacent
      tissue. These data suggest that external gamma irradiation at the single doses
      used effectively inhibits smooth muscle proliferation and intimal hyperplasia in
      the rat balloon catheter injury model in a time- and dose-dependent manner.

PMID- 7724741
TI  - Description of the chronic radiation syndrome in humans irradiated in the former
      Soviet Union.

PMID- 7724740
TI  - The antitumor effect of hyperthermia combined with fluorouracil and its
      analogues.
AB  - The effectiveness of 5-fluorouracil (5-FU), FT-207 and FT-207 + uracil in
      combination with two repetitions of 43 degrees C hyperthermia in the treatment of
      the Meth-A-Fibrosarcoma and Sarcoma-180 was examined in vivo in BALB/c mice. The
      antitumor effect was evaluated in terms of inhibition of tumor growth by
      measuring the tumor for 7 days. The 5-FU concentration in each tumor was also
      monitored. Hyperthermia combined with FT-207 or FT-207 + uracil showed a
      synergistic effect for the inhibition of growth of both tumors which was not
      observed with 5-FU. There were no significant differences in the intratumoral
      concentration of 5-FU in unheated or heated Sarcoma-180 for any drug treatment
      after the first hyperthermia treatment, except for significant decreases in the
      group given 5-FU with the first hyperthermia treatment. After the second
      hyperthermia treatment, significant decreases in the concentration of 5-FU and FT
      207 + uracil were observed. In the Meth-A-Fibrosarcoma, the intratumoral
      concentration of 5-FU decreased significantly in the group given 5-FU and
      increased significantly in the group given FT-207 + uracil after the first
      hyperthermia treatment, while there were significant decreases in 5-FU, FT-207
      and FT-207 + uracil administered with the second hyperthermia treatment.
      Hyperthermia combined with FT-207 or FT-207 + uracil is considered to be
      effective.

PMID- 7724742
TI  - On the issue of citation of "relevant" published studies in widely different cell
      systems.

PMID- 7724743
TI  - A perspective on K-space.

PMID- 7724744
TI  - Spiral CT angiography: an alternative to conventional angiography.

PMID- 7724745
TI  - Pancreatic tumors: imaging with PET.

PMID- 7724746
TI  - The natural history of lumbar spine disease.

PMID- 7724747
TI  - Hyperintense disks on T1-weighted MR images: are they important?

PMID- 7724748
TI  - Pancreatic adenocarcinoma: CT versus MR imaging in the evaluation of
      resectability--report of the Radiology Diagnostic Oncology Group.
AB  - PURPOSE: To compare findings with computed tomography (CT) and magnetic resonance
      (MR) imaging in pancreatic adenocarcinoma and to determine optimal pulse
      sequences for MR imaging. MATERIALS AND METHODS: CT scans and MR images were
      compared of 189 adult patients with known or suspected adenocarcinoma of the
      pancreas. Levels of confidence were correlated with surgical and pathologic
      results. RESULTS: The accuracy of CT was 0.73 and of MR imaging was 0.70. The
      negative predictive value of CT was 0.28 and of MR imaging was 0.23. The positive
      predictive value of CT was 0.89 and of MR imaging was 0.88. Gradient-echo and T1
      weighted spin-echo sequences ranked equally in evaluation of vascular invasion,
      T1-weighted spin-echo sequences were preferred for assessing lymphadenopathy, and
      T2-weighted spin-echo sequences were preferred for detecting hepatic metastases.
      CONCLUSIONS: Cross-sectional imaging modalities are useful in the identification
      of unresectable pancreatic carcinoma. CT is recommended for initial imaging
      assessment.

PMID- 7724749
TI  - Pancreatic neuroendocrine tumors: diagnosis with PET.
AB  - PURPOSE: To evaluate the use of carbon-11-labeled L-dihydroxyphenylalanine (L
      DOPA) and hydroxytryptophan (5-HTP) in the diagnosis of pancreatic endocrine
      tumors with positron emission tomography (PET). MATERIALS AND METHODS: Twenty-two
      consecutive patients with clinically and biochemically verified pancreatic
      endocrine tumors were examined with computed tomography (CT) and PET with L-DOPA
      alone (n = 16) or both C-11-L-DOPA and C-11-5-HTP (n = 6). RESULTS: Tumor uptake
      of L-DOPA was found in 11 patients, eight of whom had metastatic disease.
      Heterogeneity of tracer uptake was noted among different lesions in the same
      patient (ie, high uptake in some lesions and low uptake in others). Results in
      patients examined with both L-DOPA and 5-HTP correlated well, but the uptake
      levels of 5-HTP were higher in two of three patients with positive findings. In
      two additional patients, CT enabled detection of tumors not detected at PET.
      CONCLUSION: The current PET technique can be a valuable complement to CT in
      demonstration of functional pancreatic endocrine tumors, in particular,
      glucagonomas, but is less useful in detection of nonfunctional tumors.

PMID- 7724750
TI  - 2-(fluorine-18)-fluoro-2-deoxy-D-glucose PET in detection of pancreatic cancer:
      value of quantitative image interpretation.
AB  - PURPOSE: To evaluate use of positron emission tomography (PET) versus computed
      tomography (CT) in detection of pancreatic cancer and determine the value of
      quantitative and visual image interpretation of these techniques. MATERIALS AND
      METHODS: Within 8 weeks before surgery, 73 patients with suspected pancreatic
      cancer or chronic pancreatitis underwent imaging with CT and with static PET
      after injection of 250-350 MBq of 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (FDG).
      Focal FDG uptake, considered a sign of malignancy, was calculated with
      standardized uptake values (SUVs) 60 minutes after injection. RESULTS: With FDG
      PET, pancreatic carcinoma was correctly diagnosed in 41 (95%) of 43 patients, and
      chronic pancreatitis in 27 (90%) of 30 patients. With an SUV cutoff value of
      1.53, both sensitivity and specificity for detection of malignancy were 93%. With
      CT, pancreatic cancer was correctly diagnosed in 33 (80%) of 41 patients, whereas
      results in seven (26%) of 27 patients with chronic pancreatitis were false
      positive (specificity, 74%). CONCLUSION: FDG PET enabled reliable differentiation
      of pancreatic adenocarcinoma from chronic pancreatitis. The sensitivity and
      specificity of visual image interpretation with FDG PET was statistically
      significantly higher (P < .05) than with CT.

PMID- 7724751
TI  - Evaluation of pancreatic tumors with positron emission tomography and F-18
      fluorodeoxyglucose: comparison with CT and US.
AB  - PURPOSE: To assess the clinical value of positron emission tomography (PET) with
      fluorine-18-labeled fluorodeoxyglucose (FDG) for identification of pancreatic
      carcinoma. MATERIALS AND METHODS: Forty-six patients suspected of having a
      pancreatic neoplasm and who were to undergo surgery prospectively underwent FDG
      PET, computed tomography (CT), and transabdominal ultrasound (US). Endoscopic US
      was performed in 40 patients. Images were independently interpreted and compared
      with the histopathologic findings at surgery (41 patients) or with clinical
      follow-up findings (five patients). RESULTS: In 33 of 35 patients, foci of
      pancreatic carcinomas (10-100 mm in diameter) were identified as an increase in
      FDG uptake, whereas CT, transabdominal US, and endoscopic US depicted the foci in
      31, 31, and 28, cases, respectively. Among 11 benign lesions, nine showed no
      increased FDG uptake (specificity = 82%). Specificities of the other modalities
      were lower. False-positive findings were obtained in a case of chronic active
      pancreatitis and in a serous cystadenoma. CONCLUSION: FDG PET, which provides
      "biochemical" information, is accurate in identifying pancreatic carcinoma and
      may be a method of choice when imaging equivocal masses detected with other
      "anatomic" imaging studies.

PMID- 7724752
TI  - Dynamic incremental CT: effect of volume and concentration of contrast material
      and patient weight on hepatic enhancement.
AB  - PURPOSE: To develop an individualized approach to the intravenous administration
      of contrast material for hepatic computed tomography (CT). MATERIALS AND METHODS:
      Two hundred patients were randomized into eight protocols. Each group received
      different volumes and concentrations of contrast material. For each protocol,
      maximum hepatic enhancement (MHE) was calculated, with an adjustment for iodine
      dose and patient weight. The contrast enhancement index (CEI) and optimum
      scanning interval were calculated for hepatic enhancement thresholds of 10-60 HU.
      RESULTS: The MHE calculated as a function of patient weight was 96 HU +/- 19 per
      gram of iodine per kilogram of body weight. CEIs obtained with a contrast
      material concentration of 240 mg of iodine per milliliter were inferior to those
      obtained with a concentration of 320 or 350 mg I/mL. At low enhancement
      thresholds, the volume of contrast material had a more important effect than the
      concentration on CEI and optimum scanning interval; at high thresholds,
      concentration had a more important effect. CONCLUSION: For a patient of known
      weight, one can calculate the iodine dose needed to provide a desired level of
      hepatic enhancement. Use of a contrast material with a concentration of 240 mg
      L/mL is not recommended for dynamic incremental hepatic CT, except in small
      patients (eg, those weighing less than 73 kg).

PMID- 7724753
TI  - Quantitative evaluation of pancreatic enhancement during dual-phase helical CT.
AB  - PURPOSE: To determine the improvement in pancreatic enhancement at helical
      computed tomography (CT) performed with an early delay after administration of
      contrast material compared with that performed with a standard delay. MATERIALS
      AND METHODS: Dual-phase helical CT of the abdomen was performed in 120 patients
      with a 150-mL bolus of contrast material infused at 5 mL/sec. Early and standard
      delayed scanning was performed beginning at 20 seconds and 49-71 seconds,
      respectively. Regions of interest were measured in the head, body, and tail of
      the pancreas in 92 patients. The difference in enhancement between early and
      standard delayed scanning was calculated. RESULTS: Mean pancreatic enhancement
      was 82 HU +/- 3 (standard error) with an early delay, whereas enhancement on
      standard delay scans was 62 HU +/- 2 (P < .001). An improvement in enhancement
      greater than 10 HU was attained in 66 of 92 cases (72%). CONCLUSION: Pancreatic
      enhancement at helical CT with an early delay after contrast material
      administration is often significantly greater than the enhancement seen with a
      standard delay when a monophasic, rapidly infused bolus of contrast material is
      used.

PMID- 7724754
TI  - Hepatic arterial anatomy in transplantation candidates: evaluation with three
      dimensional CT arteriography.
AB  - PURPOSE: To assess the utility of three-dimensional (3D) hepatic helical computed
      tomographic (CT) arteriography as a replacement for conventional angiography in
      the evaluation of the arterial anatomy of patients being considered for liver
      transplantation. MATERIALS AND METHODS: Three-dimensional CT arteriograms were
      obtained in 115 patients. Seventeen patients also underwent conventional
      angiography, and 16 patients who did not undergo angiography underwent hepatic
      transplantation. RESULTS: Among the 3D CT arteriograms, 106 delineated the major
      arteries that supplied the liver. Nine were considered technical failures. In the
      17 patients with angiographic correlation, there was only one marked disagreement
      with 3D CT arteriography. In the 16 patients with surgical correlation, no marked
      discrepancies were found. CONCLUSION: In transplantation candidates, successful
      3D CT arteriography was as accurate as angiography in the assessment of hepatic
      arterial anatomy. It was also safer, more convenient, and more easily tolerated.
      Conventional CT plus 3D CT arteriography was only 25% as expensive as the cost of
      conventional CT and conventional angiography.

PMID- 7724755
TI  - Sonoelasticity imaging of prostate cancer: in vitro results.
AB  - PURPOSE: To compare sonoelasticity imaging versus ultrasound (US) in detection of
      prostate cancer. MATERIALS AND METHODS: Sonoelasticity imaging and US were
      performed on 10 prostatectomy specimens in which cancer was detected at previous
      biopsy. Six patients had no palpable lesions at digital rectal examination.
      Specimens were imaged axially at the apex, middle, and base of the gland to
      correlate with location of pathologic sections. All images were interpreted
      blindly and prospectively, and results were compared with pathologic findings.
      RESULTS: Sensitivity and specificity with sonoelasticity imaging were 85% and
      84%, respectively, and 30% and 100% with standard US when compared with
      pathologic findings. Sixty-four percent of pathologically confirmed tumors
      detected at sonoelasticity imaging were isoechoic on conventional US images.
      CONCLUSION: In this limited study, sonoelasticity imaging was more sensitive for
      tumor detection and more accurate for assessment of tumor location than was
      conventional US.

PMID- 7724756
TI  - Prostate cancer: effect of postbiopsy hemorrhage on interpretation of MR images.
AB  - PURPOSE: To assess the frequency of changes in signal intensity after prostatic
      biopsy and the effect of these changes on the magnetic resonance (MR) imaging
      staging of prostate cancer. MATERIALS AND METHODS: Seventy-three patients with
      biopsy-proved prostate cancer were divided into two groups according to time
      between biopsy and imaging (less than and more than 21 days). The findings at MR
      imaging were compared with those at pathologic examination. RESULTS: Postbiopsy
      hemorrhage was detected in 21 of 26 (81%) patients who underwent imaging less
      than 21 days after biopsy and in 23 of 47 (49%) patients who underwent imaging
      more than 21 days after biopsy (P < .01). Postbiopsy changes persisted for as
      long as 4 1/2 months. Less than 21 days after biopsy, there was a tendency to
      overestimate tumor presence and extracapsular extension. After 21 days, tumor
      presence was underestimated but the positive predictive value for extracapsular
      extension was improved. Staging accuracy less than 21 days after biopsy was 46%;
      this improved to 83% after 21 days (P < .01). CONCLUSION: Staging accuracy is
      significantly improved when imaging is deferred for 21 days after biopsy.

PMID- 7724757
TI  - Ovarian cancer: comparison of findings with perfluorocarbon-enhanced MR imaging,
      In-111-CYT-103 immunoscintigraphy, and CT.
AB  - PURPOSE: To determine the accuracy of breath-hold gadolinium- and perflubron
      enhanced magnetic resonance (MR) imaging, immunoscintigraphy with indium-111-CYT
      103 (planar and single photon emission computed tomography [CT]), and contrast
      material-enhanced CT for the detection of ovarian cancer prior to laparotomy.
      MATERIALS AND METHODS: Sixteen patients with primary (n = 3) or treated (n = 13)
      ovarian cancer underwent imaging of the abdomen and pelvis with each modality.
      All images were reviewed prospectively for tumor location, and results were
      compared with findings at surgery. RESULTS: With CT or MR imaging, tumor was
      detected in 11 of 13 (85%) patients compared with 11 of 12 patients (92%) with
      immunoscintigraphy. Per patient accuracy for CT was 81% compared with 75% for MR
      imaging and 86% for immunoscintigraphy. For detection of individual sites of
      tumor, the sensitivity of MR imaging was highest (81%) compared with CT (51%, P <
      .001) and immunoscintigraphy (50%, P < .01). The combination of MR imaging and
      immunoscintigraphy depicted 89% of sites of tumor involvement confirmed at
      laparotomy. CONCLUSION: MR imaging and immunoscintigraphy show promise for the
      evaluation of patients with ovarian cancer.

PMID- 7724759
TI  - Soft-tissue sarcomas: MR imaging findings after treatment in three pediatric
      patients.
AB  - PURPOSE: To characterize the skeletal and bone marrow magnetic resonance (MR)
      imaging changes during and after treatment of childhood soft-tissue tumors.
      MATERIALS AND METHODS: Three boys with soft-tissue sarcomas of the popliteal
      fossa underwent surgery, radiation therapy, and chemotherapy. Plain radiographic
      and MR imaging findings were correlated with the effect of treatment. RESULTS:
      After radiation therapy, MR images revealed findings that resembled those of
      rickets at sites of irradiation in the three patients. These findings included
      metaphyseal sclerosis, metaphyseal fraying, and epiphyseal plate widening. Bone
      marrow imaging changes were temporally related to therapy. During chemotherapy,
      reconversion to hematopoietic marrow was noted in nonirradiated areas in two
      patients, but after cessation of all treatment, these areas converted back to
      fatty marrow. Irradiated areas of bone marrow remained fatty throughout therapy
      in the three patients. CONCLUSION: Awareness of the MR imaging findings related
      to antineoplastic treatment of soft-tissue tumors is important to distinguish
      these changes from progression of primary disease.

PMID- 7724758
TI  - Renovascular hypertension in children: curability predicted with negative
      intrarenal Doppler US results.
AB  - PURPOSE: To assess whether intrarenal Doppler ultrasound (US) enables prediction
      of the outcome of renovascular hypertension in a pediatric population. MATERIALS
      AND METHODS: A prospective study of 29 children with renin-mediated hypertension
      was performed. In these patients, intrarenal Doppler US was performed before
      angiography. Doppler US and angiographic findings were compared with patient
      outcome with respect to treatment required and blood pressure (BP) status after
      therapy. Cure was defined as a normal BP without medication. RESULTS: Intrarenal
      Doppler US was positive in 15 patients (52%), group 1, and negative in 14
      patients (48%), group 2. In 10 patients (67%) in group 1, the severity of the
      vascular lesion precluded permanent cure. Cure was achieved in all patients in
      group 2, except for patients with neurofibromatosis. Thus, there was a
      statistically significant association (P < .05) between cure and a negative
      Doppler US result. CONCLUSION: In children with renovascular hypertension, a
      negative Doppler US result enables the prediction that a cure is more likely to
      be achieved with endovascular therapy or surgery.

PMID- 7724760
TI  - Major geometric variations between multiple high-dose-rate applications of
      brachytherapy in cancer of the cervix: frequency and types of variation.
AB  - PURPOSE: To evaluate major geometric variations in multiple intracavitary
      applications for carcinoma of the cervix. MATERIALS AND METHODS: Orthogonal
      radiographs were reviewed of 17 consecutive patients with carcinoma of the cervix
      treated with 70 applications of high-dose-rate brachytherapy. In seven patients,
      conscious sedation was used for all applications. In 10 patients, general
      anesthesia was used for the first application and conscious sedation for
      subsequent applications. Major geometric variation between applications in axis,
      length, and slippage in tandem placement and separation, packing, and slippage in
      colpostats placement were reviewed. A major variation was defined as more than
      1.0-cm deviation. RESULTS: Major variations between applications occurred more
      commonly in colpostats placement than in tandem placement. For tandems, the rates
      of variation were 5.7% in axis, 4.3% in length, and 1.4% in slippage. For
      colpostats, rates of variation were 7.1% in separation, 25.7% in vaginal packing,
      and 7.1% in slippage. No consistent pattern of variation was found between
      applications except in vaginal packing. CONCLUSION: Awareness of geometric
      variations should improve proper placement of intracavitary applicators for
      brachytherapy.

PMID- 7724761
TI  - Ocular trauma: evaluation with US.
AB  - PURPOSE: To examine the value of real-time ultrasonography (US) in the assessment
      of traumatized eyes with opaque ocular media. MATERIALS AND METHODS: Sixty-one
      eyes in 60 patients were prospectively examined with US; findings were correlated
      with findings of clinical and surgical follow-up. Patients with an intraocular
      foreign body (IOFB) also underwent computed tomography (CT). RESULTS: US
      demonstrated 56 vitreous hemorrhages, 21 retinal detachments, 12 vitreous
      detachments, five choroidal detachments, seven IOFBs, three dislocated lenses,
      and two retrohyaloid hemorrhages. Findings of US and surgery or clinical follow
      up were in complete concurrence in 55 cases (90%) and partial concurrence in two
      cases (3%). US findings were incorrect in four cases (7%). In four cases, US
      allowed diagnoses that were unsuspected clinically. CONCLUSION: US accurately
      demonstrates ocular damage and may reveal unsuspected problems. US was superior
      to CT in demonstration of intraocular damage associated with IOFBs, although CT
      was superior in determination of the size and site of the IOFB. The presence of
      dense vitreous traction bands may indicate impending retinal detachment.

PMID- 7724762
TI  - Contrast-enhanced MR imaging in acute lumbar radiculopathy: a pilot study of the
      natural history.
AB  - PURPOSE: To prospectively study clinical findings and contrast material-enhanced
      magnetic resonance (MR) images over time in patients with acute lumbar
      radiculopathy. MATERIALS AND METHODS: Twenty-five patients underwent physical
      examination and MR imaging at presentation, 6 weeks, and 6 months. Initial
      symptoms and clinical course were correlated with type, size, location, and
      enhancement of disk herniations. RESULTS: Eighteen patients had a herniated
      nucleus pulposus (HNP) at one or more levels, two had synovial cysts and
      stenosis, and five had normal findings. Patients with an HNP had marginally more
      severe neurologic symptoms than did patients without an HNP (P = .07) at
      presentation. Twenty-two patients completed the 6-week examinations and 14
      patients the 6-month examinations; three patients were eliminated from the study
      after surgical treatment. Among HNPs larger than 6 mm, substantial reduction in
      size was noted in 36% at 6 weeks and in more than 60% at 6 months after
      presentation. CONCLUSION: Agreement between clinical and MR findings for level
      and side of HNP and radicular symptoms was excellent. There was no correlation of
      pain and disability with disk size, behavior, or type.

PMID- 7724763
TI  - Hyperintense disks on T1-weighted MR images: correlation with calcification.
AB  - PURPOSE: To determine if calcification in the intervertebral disk is associated
      with hyperintensity on T1-weighted spin-echo magnetic resonance (MR) images.
      MATERIALS AND METHODS: Sagittal T1-weighted MR images that showed one or more
      hyperintense intervertebral disks and correlative computed tomographic (CT)
      scans, plain radiographs, or both, were obtained in 11 patients retrospectively
      and in 43 patients prospectively. Six patients underwent MR imaging with a fat
      suppression technique. Histologic analysis of two disks was performed. RESULTS:
      Absence of calcification was associated with disks that were isointense relative
      to normal disks (P < .001), mild to moderate calcification was associated with
      hyperintense disks (P < .001 and P = .004 [two readers]), and both mild to
      moderate and marked calcifications were associated with hypointense disks (P <
      .001). Fat suppression resulted in a decrease in hyperintense signal in two
      patients. CONCLUSION: The results indicate that hyperintensity is associated with
      calcification. In the absence of clinical findings that suggest other causes,
      hyperintense disks are suggestive of degenerative disk disease.

PMID- 7724764
TI  - Circle of Willis: evaluation with spiral CT angiography, MR angiography, and
      conventional angiography.
AB  - PURPOSE: To evaluate the use of spiral computed tomographic (CT) angiography in
      the analysis of the arteries of the circle of Willis and compare these results
      with magnetic resonance (MR) angiography and conventional angiography. MATERIALS
      AND METHODS: The results in 17 patients who underwent examination were
      prospectively studied in a blinded fashion. The presence or absence of the
      arteries of the circle of Willis was determined by using maximum intensity
      projection reconstructions from CT angiography and MR angiography. These results
      were compared with results from conventional angiography. RESULTS: Similar
      sensitivities were determined for CT angiography (88.5%) and MR angiography
      (85.5%); however, MR angiography was found to differ significantly (P = .005)
      from conventional angiography. No significant differences (P > .05) were found
      between the two modalities and conventional angiography in the detection of the
      anterior, middle, or posterior cerebral arteries or the anterior communicating
      artery. CONCLUSION: Spiral CT angiography is highly sensitive in the detection of
      arterial anatomy in the circle of Willis and is a reliable alternative to MR
      angiography.

PMID- 7724765
TI  - Intracranial arteries: prospective blinded comparative study of MR angiography
      and DSA in 50 patients.
AB  - PURPOSE: To compare the reliability of magnetic resonance (MR) angiography
      performed with magnetization transfer suppression and variable flip angle
      excitation with that of intraarterial digital subtraction angiography (DSA) in
      imaging of the cerebral arteries. MATERIAL AND METHODS: Fifty nonconsecutive
      patients referred for intraarterial DSA gave informed consent to also undergo MR
      angiography of the intracranial arteries. RESULTS: MR angiography had a
      sensitivity of 100% and a specificity of 95% for detection of vessel occlusion
      (10 abnormalities). For detection of substantial vessel stenosis (seven
      abnormalities), sensitivity and specificity were both 86%; for detection of
      aneurysm (six abnormalities), sensitivity was 83% and specificity was 98%.
      Sensitivity and specificity were 100% for detection of arteriovenous malformation
      (three abnormalities), vessel displacement (three abnormalities), and
      extracranial-intracranial bypass (two abnormalities). MR angiography did not
      reliably demonstrate small feeding vessels of a tumor or faint residual perfusion
      of a thrombosed aneurysm. CONCLUSION: MR angiographic diagnosis of disease of the
      intracranial vasculature has high sensitivity and specificity but still is
      limited in comparison with intraarterial DSA.

PMID- 7724766
TI  - Assessment of living renal donors with spiral CT.
AB  - PURPOSE: To determine whether spiral computed tomography (CT) can be used to
      evaluate potential living renal donors. MATERIALS AND METHODS: Twelve potential
      living renal donors underwent spiral CT and conventional arteriography. CT
      angiography was performed with 30-second spiral acquisition during injection of
      150 mL of nonionic iodinated contrast material into an antecubital vein at 5
      mL/sec. Five minutes after injection, a frontal abdominal scout projection was
      obtained to assess the renal collecting system. Results of blinded
      interpretations of axial CT angiograms, three-dimensional CT angiograms, and
      conventional arteriograms were correlated with intraoperative findings in 11
      cases. RESULTS: Axial and three-dimensional CT angiography were 100% sensitive
      for identifying seven accessory renal arteries and 14% and 93% sensitive for
      identifying five prehilar renal artery branches. Renal venous anomalies were
      confirmed in three patients at surgery. Operative management changed in four of
      11 patients who underwent donor nephrectomy. CONCLUSION: Spiral CT holds promise
      as a single examination for anatomic assessment of living renal donors.

PMID- 7724767
TI  - Incidence of pseudoaneurysm after diagnostic and therapeutic angiography.
AB  - PURPOSE: To investigate prospectively with color flow duplex (CFD) sonography the
      incidence of pseudoaneurysm or arteriovenous fistula (AVF) after transfemoral
      arterial catheterization with angiography, percutaneous transluminal angioplasty
      (PTA), or local lysis (LL). MATERIALS AND METHODS: CFD sonography was used to
      examine the puncture site in 565 consecutive patients who had undergone PTA, LL,
      or angiography (581 procedures). RESULTS: The incidence of pseudoaneurysm in the
      first 300 procedures in which standard compression was used was 14.0% overall,
      27.0% after LL with antegrade-puncture PTA, 18.5% after antegrade-puncture PTA,
      9.3% after retrograde-puncture PTA, and 1.2% after angiography. To decrease the
      high incidence, in the next 281 procedures manual compression was continued for
      at least 5 minutes after local bleeding had stopped. This significantly reduced
      the incidence to 1.1% overall, 8.0% after LL in combination with PTA, 0.9% after
      antegrade PTA alone, 0.9% after retrograde PTA, and 0% after angiography (P <
      .01). CONCLUSION: The incidence of pseudoaneurysm after transfemoral arterial
      catheterization depends on the type of intervention. The main risk factor is too
      brief a period of manual compression.

PMID- 7724768
TI  - Azygos venous blood flow: measurement with direct bolus imaging.
AB  - PURPOSE: To evaluate a magnetic resonance (MR) imaging technique for measurement
      of azygos blood flow volume, which is an important indicator of superior
      collateral circulation in patients with portal hypertension. MATERIALS AND
      METHODS: Azygos blood flow was measured by means of direct bolus (DB) imaging, an
      MR flow measurement technique. A presaturation pulse was applied in combination
      with electrocardiographic gating. RESULTS: The measured flow volume was 320
      mL/min +/- 30 (mean +/- standard error of mean) in the control subjects, 550
      mL/min +/- 130 in patients with cirrhosis of the liver and without varices, and
      660 mL/min +/- 60 in patients with cirrhosis of the liver and with varices. The
      flow volume was significantly higher in each of the groups with cirrhosis of the
      liver than in the control group (P < .01). Furthermore, a significant correlation
      was shown between DB imaging and continuous thermodilution measurements (r =
      .707, P < .01). CONCLUSION: DB imaging, which is noninvasive, was useful in the
      monitoring of the effect of treatment and in determination of the prognosis in
      patients with portal hypertension.

PMID- 7724770
TI  - Use of Wallstents for hemodialysis access-related venous stenoses and occlusions
      untreatable with balloon angioplasty.
AB  - PURPOSE: To determine whether the Wallstent endoluminal prosthesis can be used to
      maintain patency of venous stenoses and occlusions related to hemodialysis
      access. MATERIALS AND METHODS: Wallstents were placed in 52 patients with 56
      lesions. Thirty-two lesions were in central veins and 24 were in peripheral
      veins. Stents were placed immediately after failed angioplasty in 39 patients,
      because of early restenosis after angioplasty in four, and for treatment of a
      lesion unsuitable for angioplasty in eight. The remaining five lesions were
      treated at the operator's discretion after predilation. RESULTS: The procedural
      success rate was 96%. The cumulative primary patency rate was 46% at 6 months and
      20% at 12 months; however, with repeat treatment, the cumulative assisted patency
      rate was 76% at 6 months and 33% at 12 months. Known causes of recurrence
      included intimal hyperplasia in or near the stent, stent slippage, and remote
      stenoses. Complications included two stent migrations due to central line
      placement and one stent-related pseudoaneurysm. CONCLUSION: Wallstents are safe
      to deploy for dialysis access. Wallstents are useful for treating lesions that
      fail angioplasty and catheter-related central venous occlusions.

PMID- 7724769
TI  - Improved ejection fraction and flow velocity estimates with use of view sharing
      and uniform repetition time excitation with fast cardiac techniques.
AB  - PURPOSE: To improve the accuracy of ventricular volume estimates and effective
      temporal resolution in fast cardiac acquisitions. MATERIALS AND METHODS: Data
      sets at intermediate temporal phases were generated by means of sharing of views
      from two temporally adjacent data sets. A simulated model was used, and studies
      with patients and volunteers were conducted. View sharing was implemented in both
      fast gradient-echo and fast phase-contrast cine acquisitions; breath holding was
      used when possible. RESULTS: Uniform repetition time (TR) radio-frequency (RF)
      excitation allowed a better assessment of the end-diastolic ventricular volume.
      In addition, view sharing provided a better estimate of end-systolic ventricular
      volume in cases in which rapid changes in volume occurred at or about the
      temporal boundary of the source images. View sharing also provided a much
      smoother representation of dynamic cardiac motion when viewed in a cine loop.
      CONCLUSION: View sharing and uniform TR RF excitation improve the accuracy of end
      systolic and end-diastolic ventricular volume measurements by improving the
      effective temporal resolution.

PMID- 7724771
TI  - Intentional reversible thrombosis of transjugular intrahepatic portosystemic
      shunts.
AB  - PURPOSE: To assess whether balloon occlusion of a transjugular intrahepatic
      portosystemic shunt (TIPS) will allow permanent yet reversible shunt thrombosis.
      MATERIALS AND METHODS: A balloon catheter was inflated in the midportion of the
      TIPS in two women with severe, uncontrollable encephalopathy or liver failure
      (aged 42 and 65 years, respectively) to allow occlusive thrombus to develop below
      the balloon. RESULTS: Balloon occlusion led to rapid TIPS thrombosis, which was
      readily reversible. CONCLUSION: Balloon thrombosis is a simple technique for
      complete occlusion of a TIPS. This technique may also be useful for occlusion of
      surgical mesocaval H-graft shunts or dialysis access shunts.

PMID- 7724772
TI  - Clinical results with Resovist: a phase 2 clinical trial.
AB  - PURPOSE: To investigate the superparamagnetic iron oxide (Resovist) designed for
      contrast material-enhanced magnetic resonance imaging of the liver. MATERIALS AND
      METHODS: A phase 2 trial was performed in 33 patients with no more than five
      known focal solid liver lesions. Resovist was administered intravenously at doses
      of 4, 8, and 16 mumol of iron per kilogram of body weight. Postcontrast 1.0-T
      imaging was started 30 minutes after injection. RESULTS: Resovist significantly
      (P < or = .05) decreased liver signal intensity and increased lesion-to-liver
      contrast-to-noise ratio (C/N) and the number of detectable liver lesions: fast
      spin-echo (SE) (echo time, 90 msec) precontrast C/N, 11.7 +/- 7.9 [standard
      deviation]; postcontrast [8-mumol Fe/Kg] C/N, 29.2 +/- 14.2). The dose of 8 mumol
      Fe/kg was sufficient for the detection of focal liver lesions, and T2-weighted
      fast SE with an echo time of 90 msec was the overall best pulse sequence.
      CONCLUSION: Resovist is a safe contrast agent, and a dose of 8 mumol Fe/kg is
      sufficient to enhance detection of focal liver lesions at T2-weighted fast SE MR
      imaging.

PMID- 7724773
TI  - Rotator cuff tendon tears: evaluation with fat-suppressed MR imaging with
      arthroscopic correlation in 100 patients.
AB  - PURPOSE: To evaluate the diagnostic accuracy of fat-suppressed magnetic resonance
      (MR) imaging of rotator cuff tears in a large symptomatic population. MATERIALS
      AND METHODS: One hundred patients underwent both MR imaging and arthroscopy of
      the shoulder. Ninety-two patients underwent fat-suppressed conventional spin-echo
      MR imaging (repetition time msec/echo time msec = 2,500/20, 60), and eight
      patients underwent fat-suppressed, fast spin-echo MR imaging (2,000/80). RESULTS:
      With data combined for complete and partial tears of the rotator cuff (n = 31),
      MR imaging had an accuracy of 93%; sensitivity, 84%; and specificity, 97%.
      Seventeen of 20 complete tears and nine of 11 partial tears were properly
      identified with MR imaging. Two partial tears were not detected and three
      complete tears were incorrectly called partial tears at MR imaging. Of two false
      positive MR imaging findings, one was called a complete tear and the other, a
      partial tear. CONCLUSION: Fat-suppressed MR imaging has high diagnostic accuracy
      in evaluating tears of the rotator cuff tendon.

PMID- 7724774
TI  - Acromial arch shape: assessment with MR imaging.
AB  - PURPOSE: To test the hypothesis that acromial shape is comparable on
      supraspinatus outlet view radiographs and parasagittal magnetic resonance (MR)
      images. MATERIALS AND METHODS: Supraspinatus outlet view radiographs of a dried
      scapula were obtained in the neutral position and with various degrees of caudal,
      cranial, anterior, and posterior angulation. Sagittal MR images of 41
      asymptomatic and 39 symptomatic shoulders were reviewed and compared with outlet
      view radiographs from the 39 symptomatic cases. Acromial shape was assessed with
      published classification schemes. RESULTS: Minor variations in angulation
      produced changes in apparent acromial shape and thickness on the radiographs. MR
      imaging from a lateral to a more medial section changed the shape or thickness
      grade in 39 of 41 asymptomatic shoulders. There was poor correlation between
      findings at radiographic and MR assessment of acromial shape in the symptomatic
      group. CONCLUSION: Apparent acromial shape is sensitive to minor changes in
      radiographic technique and MR section viewed.

PMID- 7724776
TI  - Intraosseus ganglia of the wrist.
AB  - PURPOSE: To determine the prevalence of intraosseous ganglion cysts in patients
      with unexplained wrist pain and evaluate the radiographic methods used for their
      detection. MATERIALS AND METHODS: Four hundred patients with unexplained wrist
      pain were prospectively examined. All patients underwent standard three-view
      radiography of the wrist. Patients with cystic areas on conventional radiographs
      underwent further examination with bone scanning. Ultimately, 17 patients whose
      bone scans demonstrated increased radiotracer uptake that localized to a
      particular carpal bone underwent magnetic resonance (MR) imaging. RESULTS: Of
      these 17 patients, intraosseous ganglion cysts were diagnosed in 15. Some of
      these ganglia were occult on conventional radiographs and were detected only at
      bone scanning and MR imaging. CONCLUSION: Intraosseous ganglion cysts in the
      wrist are more common than previously reported. In some patients, bone scanning,
      conventional radiography, and/or MR imaging will aid surgical resection that
      could provide symptomatic relief of unexplained wrist pain.

PMID- 7724775
TI  - Subungual glomus tumors: evaluation with MR imaging.
AB  - PURPOSE: To determine the magnetic resonance (MR) imaging features of subungual
      glomus tumors. MATERIALS AND METHODS: Thirty-one patients with a clinical
      suspicion of glomus tumor and 10 control subjects underwent MR imaging at 1.5 T.
      MR images of normal glomus bodies of a cadaver finger were correlated with
      histologic slices. With a local surface gradient coil, the pixel size reached 117
      microns in one direction. Relaxation times were measured. Gadoterate meglumine
      was injected in 19 patients. RESULTS: Normal glomus bodies were visualized in the
      reticular dermis of the nail bed. Twenty-seven of 28 pathologically confirmed
      glomus tumors were detected with MR imaging. A peripheral capsule was present in
      most tumors. The nail matrix was compressed in 13 cases. The authors were able to
      differentiate three subtypes of glomus tumors (vascular, solid, and myxoid) on
      the basis of relaxation times and enhancement characteristics. Four patients had
      mucoid cysts or angioma in the nail bed. CONCLUSION: MR imaging can help
      accurately define the location and limits of glomus tumors before excision.

PMID- 7724777
TI  - Triangular fibrocartilage complex: normal appearance on coronal three-dimensional
      gradient-recalled-echo MR images.
AB  - PURPOSE: To evaluate the usefulness of three-dimensional gradient-recalled-echo
      (GRE) sequences in demonstration of the triangular fibrocartilage complex (TFCC).
      MATERIALS AND METHODS: Appearance of the TFCC in wrists of 11 cadavers, 17
      patients, and six volunteers at three-dimensional GRE magnetic resonance (MR)
      imaging was evaluated and compared with that at dissection. RESULTS: MR
      appearance of the TFCC was similar for all wrists. Volar and dorsal radioulnar
      ligaments were identified. The TFCC had two types of attachments to the ulna: The
      more common consisted of two striated attachments, one to the tip and the other
      to the base of the styloid; the less common consisted of a broad-based striated
      attachment along the styloid. MR appearance of the ulnotriquetral and ulnolunate
      ligaments and meniscus homologue varied but correlated with observations at
      dissection. CONCLUSION: The three-dimensional GRE sequence consistently
      demonstrated most TFCC components. Dissection helped confirm MR-demonstrable
      variability in the ulnar aspect of the TFCC.

PMID- 7724778
TI  - U.S. screening mammography services with mobile units: results from the National
      Survey of Mammography Facilities.
AB  - PURPOSE: To investigate elements of mobile facilities for mammography in the
      United States. MATERIALS AND METHODS: The prevalence and performance of mobile
      facilities for mammography in the United States were studied with regard to cost,
      price, quality assurance, and access. Data were acquired from the National Cancer
      Institute's National Survey of Mammography Facilities, conducted in 1992.
      RESULTS: Of the 1,057 facilities surveyed, 2.4% were identified as mobile and
      accounted for 3% of mammography examinations performed. All mobile facilities
      reported accreditation by the American College of Radiology, and 92% were in
      Statistically Metropolitan Areas. Most were affiliated with community hospitals
      or private radiology practice and were more likely to be associated with lower
      fees, convenient operating hours, batch interpretation, and computerized
      reporting than were their stationary counterparts. CONCLUSION: Mobile mammography
      facilities compare favorably with stationary facilities. The use of these mobile
      units in the United States, however, has been limited.

PMID- 7724779
TI  - MR imaging-guided breast intervention: experience with two systems.
AB  - PURPOSE: To evaluate two different systems for magnetic resonance (MR) imaging
      guided breast intervention. MATERIALS AND METHODS: Thirty-four patients with 34
      lesions detected exclusively with contrast material-enhanced MR imaging underwent
      51 interventional procedures (23 needle biopsies and 28 preoperative wire
      localizations) with two different systems. An add-on device for surface coils was
      used in 25 cases, and a dedicated single breast biopsy coil was used in 26. For
      needle biopsies, material was aspirated with nonmagnetic 19.5-gauge needles. For
      preoperative localizations, nonmagnetic hook wires were used. RESULTS: Surgical
      excision or follow-up verified the cytologic findings in 19 of the 23 cases
      sampled for biopsy. Cytologic diagnosis was impossible in three of the 23 cases.
      One technical failure occurred with the biopsy coil. Open biopsy performed after
      MR imaging-guided localization successfully removed 26 of the 28 lesions. One
      missed carcinoma was found at repeat localization and removed. One technical
      failure occurred with the biopsy coil. In that case, the lesion was close to the
      chest wall. CONCLUSION: Both systems are suitable for fine-needle biopsy and
      preoperative localization of lesions seen exclusively on MR images.

PMID- 7724780
TI  - Complications after emergency tube thoracostomy: assessment with CT.
AB  - PURPOSE: To assess the spectrum of complications after emergency tube
      thoracostomy (TT) and show the role of computed tomography (CT) in detection of
      these abnormalities. MATERIALS AND METHODS: CT scans, chest radiographs, and
      clinical data were reviewed in 51 patients (77 tubes) who underwent emergency TT
      after trauma. CT scans were analyzed for chest tube malposition (CTM) and
      persistent pneumo- or hemathoraces. RESULTS: The complication most often seen
      after emergency TT, as demonstrated with CT, was CTM (20 of 77 tubes [26%]). Only
      seven of the CTMs seen at CT were evident on chest radiographs. Two extrathoracic
      and 18 intrathoracic (five intraparenchymal, nine intrafissural) malpositioned
      tubes were seen at CT. Other findings included persistent pneumo-and hemathoraces
      in 16 patients. CONCLUSION: Patients undergoing emergency TT are at increased
      risk for complications. CTM is the most common abnormality and should be
      diagnosed promptly to prevent additional problems. CT is more useful than plain
      radiography for establishing a diagnosis.

PMID- 7724781
TI  - AIDS-related Kaposi sarcoma of the lung: radiographic findings and staging system
      with bronchoscopic correlation.
AB  - PURPOSE: To determine the chest radiographic findings in patients with
      tracheobronchial Kaposi sarcoma (KS) and to develop a radiographic staging system
      that allows comparison of radiographic to bronchoscopic findings and allows
      assessment of the typical temporal progression of pulmonary KS. MATERIALS AND
      METHODS: The chest radiographs and medical records of 76 male patients, aged 23
      60 years (mean, 36 years 4 months) with bronchoscopically proved KS were
      retrospectively reviewed. Tumor extent at bronchoscopy (grade 1-3) was compared
      with severity of parenchymal disease (radiographic stage 0-3). RESULTS: There was
      a statistically significant relationship between extent of tracheobronchial
      disease and radiographic stage (P = .01). However, in some patients, parenchymal
      KS of advanced stage was present with no visible endobronchial disease.
      CONCLUSION: The proposed staging system describes features of early, moderate,
      and advanced KS. Although there is a correlation between tracheobronchial and
      parenchymal disease, the latter can occur in the absence of endobronchial
      lesions.

PMID- 7724782
TI  - Cardiophrenic varices in portal hypertension: evaluation with CT.
AB  - PURPOSE: To determine the prevalence and appearance of cardiophrenic angle (CPA)
      varices at computed tomography (CT) in patients with portal hypertension (PHT).
      MATERIALS AND METHODS: A retrospective review was performed of 148 consecutive
      contrast material--enhanced abdominal CT scans of patients with PHT. The
      paracardiac region was assessed for tubular structures suggestive of varices.
      Variceal diameter and CT attenuation relative to adjacent liver were noted.
      RESULTS: Tubular structures consistent with CPA varices were noted in 29 cases
      and were more common on the right side than on the left. Mean CPA variceal
      diameter was 2.6 mm. In three cases, right CPA varices measured 10-13 mm in
      diameter, but no variceal enhancement was noted on initial dynamic CT images.
      Delayed CT demonstrated contrast enhancement that reflected delayed enhancement
      of the portal venous system. CONCLUSION: CPA varices, particularly on the right
      side, are not uncommon in patients with PHT. Varices should be considered and
      excluded as a cause of CPA masses, particularly before percutaneous biopsy.
      Delayed CT may be necessary to correctly delineate CPA varices.

PMID- 7724783
TI  - Radiation exposure of patients who undergo CT of the trunk.
AB  - PURPOSE: To determine the radiation dose delivered to organs during standard
      computed tomographic (CT) examination of the trunk. MATERIALS AND METHODS: In
      vivo locations and sizes of specific body organs were determined from CT images
      of patients who underwent examinations. The corresponding CT investigations were
      then simulated on an anthropomorphic phantom. The resulting doses were measured
      at 70 different sites inside the phantom by using thermoluminescent dosimeters.
      On the basis of measurements of free-in-air air kerma at the rotation axis of the
      CT gantry, conversion factors were calculated so that measurements could be used
      with different models of CT equipment. RESULTS: Starting from the dose values
      recorded, the mean organ doses were determined for 21 organs. The skin received
      22-36 mGy; the lungs, less than 1-18 mGy; the kidneys, 7-24 mGy; and the ovaries,
      less than 1-19 mGy, depending on the type of CT examination performed.
      CONCLUSION: These values are high compared with other x-ray examinations and
      should be minimized as much as possible. The number of tomographic sections
      obtained should be kept as low as possible according to diagnostic need.

PMID- 7724785
TI  - A simple method of duct cannulation and localization for galactography before
      excision in patients with nipple discharge.
AB  - A monofilament polypropylene guiding suture was inserted into a secreting duct in
      72 female patients (aged 15-78 years) with nipple discharge. Cannulation and
      injection of contrast material was successful in all patients before
      galactography and of methylene blue dye before excision. Patients did not report
      discomfort, no injuries ensued, and no duct was perforated. This technique should
      expedite excision of a discharging duct and any lobules.

PMID- 7724786
TI  - Device to enhance visibility of needle or catheter tip at color Doppler US.
AB  - The authors tested a device that allows the tip of a needle to be visualized at
      color Doppler ultrasonography. The device directs an oscillating air column
      through a 0.016-inch inner-diameter hollow stylet, creating movement at only the
      needle tip. The movement is reliably and accurately displayed as a beacon of
      color at depths of 15 cm in vitro.

PMID- 7724784
TI  - Correction of distortion in US images caused by subcutaneous tissues: results in
      tissue phantoms and human subjects.
AB  - PURPOSE: To correct distortion in ultrasonic images caused by refraction at fat
      muscle interfaces in the subcutaneous tissues. MATERIALS AND METHODS: A forward
      propagation technique was developed that used a priori information of the
      acoustic properties of the layers. The thickness and shape of these tissues were
      measured, and a correction was applied for the different velocities in the
      tissues. A synthetic-aperture scanning technique was used to allow correction to
      be applied with data obtained in a single scan. The technique was tested in three
      tissue phantoms with overlying aberrating layers (six images) and in eight
      volunteer subjects (37 images). The superior mesenteric artery and the aorta were
      used as test sites within the body, because it is relatively easy to obtain
      double images of these vessels owing to refraction of the scanning beam by the
      rectus muscles. RESULTS: Distortions such as double-image artifacts and texture
      disruption were corrected with use of this technique. Six of the six phantom
      images and 22 of the 37 images in humans were corrected with use of this
      technique. CONCLUSION: The forward-propagation technique compensates for
      refraction at subcutaneous fat-muscle interfaces.

PMID- 7724787
TI  - Fat tissue: relationship between chemical shift and magnetization transfer.
AB  - The middle calves of the legs of 25 volunteers (12 men and 13 women, aged 18-25
      years), as well as phantoms, were examined with 1.5-T magnetic resonance imaging.
      Gradient-recalled technique was combined with magnetization transfer contrast
      (MTC) and chemical shift imaging. Periodic oscillation of the MTC effect in fat
      tissue with variation of echo time was identified at the frequency corresponding
      to the water-fat chemical shift difference.

PMID- 7724788
TI  - Breast and chest wall hemorrhage after routine mammography in a patient receiving
      heparin.

PMID- 7724789
TI  - Painful transient tibial edema.

PMID- 7724790
TI  - Morison pouch.

PMID- 7724791
TI  - In defense of a missed lesion.

PMID- 7724793
TI  - Failure to obtain informed consent to surgery. Case in point: Butler v. South
      Fulton Medical Center, Inc. 452 S.E.2d 768--GA (1994).

PMID- 7724792
TI  - Nurses delay reporting paralysis: "Loss of Chance".

PMID- 7724794
TI  - Legal case briefs for nurses. NY: patients with same name misidentified: failure
      to timely notify spouse of death; NY: home health care rep a no-show: injured pt.
      sues--waiver against public policy.

PMID- 7724795
TI  - Can a nurse be individually liable for violating EMTALA? Case in point: Repp v.
      Anadarko Mun. Hosp. 43 F. 3d 519--OK (1994).

PMID- 7724796
TI  - Neural mechanisms involved in the corticosteroid feedback effects on the
      hypothalamo-pituitary-adrenocortical axis.

PMID- 7724797
TI  - Can computers think? Differences and similarities between computers and brains.

PMID- 7724798
TI  - [Scientific achievement of Professor Shiro Akabori].

PMID- 7724799
TI  - Shiro Akabori--October 20, 1900-November 3, 1992.

PMID- 7724800
TI  - [Studies on the Src protein].

PMID- 7724801
TI  - [Search for a regulatory system common to neurogenesis, oncogenesis and immune
      response].

PMID- 7724802
TI  - [Neuronal apoptosis].

PMID- 7724803
TI  - [A search for new functions of proteins].

PMID- 7724804
TI  - [Iron-sulfur electron transfer protein and assimilation of inorganic compounds in
      plants].

PMID- 7724805
TI  - [Pistil RNases and gametophytic self-incompatibility].

PMID- 7724806
TI  - [Chemical synthesis of proteins].

PMID- 7724807
TI  - [Recent advance in X-ray protein crystallography].

PMID- 7724808
TI  - [NMR studies on structure and interaction of proteins and nucleic acids in
      solution].

PMID- 7724810
TI  - [New aspects of electrophoresis and concern about manufacturing].

PMID- 7724809
TI  - [Mass spectrometry of proteins].

PMID- 7724811
TI  - [Sodium channel functioning based on an octagonal structure model].

PMID- 7724812
TI  - [Amino-terminal processing of nascent proteins: their rule and implication on
      biological function].

PMID- 7724813
TI  - [Structure and expression of an inducible prostaglandin endoperoxide synthase
      gene].

PMID- 7724814
TI  - [The trend of Simons Lab. in EMBL].

PMID- 7724815
TI  - [Non-linear response applied to chemical sensor--structure of taste-smell model
      system].

PMID- 7724816
TI  - Rapid MR imaging of the liver: comparison of twelve techniques for single breath
      hold whole volume acquisition.
AB  - Twelve magnetic resonance imaging pulse sequences for single breath-hold whole
      volume acquisition of the liver were evaluated on volunteers. Liver and spleen
      contrast to noise ratio (C/N), overall image quality, and grade of artifacts were
      compared. The 12 sequences included T2-weighted fast spin echo (FSE) with or
      without fat suppression (FS), fast multiplanar spoiled gradient recalled imaging
      (FMPSPGR), fast gradient recalled imaging without preparation pulses (FGR), FGR
      with inversion recovery preparation pulse nulling the liver or fat (IR-FGR-L and
      IR-FGR-F), FGR with driven equilibrium preparation pulse (DE-FGR), single shot
      moderately or heavily T2-weighted spin echo echo planar imaging (SE-EPI-mT2 and
      SE-EPI-hT2), multi-shot moderately T2-weighted spin echo echo planar imaging
      (multi-shot SE-EPI-mT2), inversion recovery EPI, and gradient echo EPI. In the
      quantitative analysis, FSE + FS showed a significantly higher C/N ratio than the
      others (p < 0.05). In the qualitative evaluation, DE-prepFGR, and single and
      multi-shot SE-EPI-mT2 had good results, as did FSE and FSE + FS. Further studies
      should be conducted to determine whether or not these breath-hold sequences can
      obviate current conventional non-breath-hold sequences.

PMID- 7724817
TI  - Nodular lesions in renal tuberculosis.
AB  - We retrospectively studied the CT findings of renal tuberculosis in 27 cases (32
      kidneys). As a characteristic CT finding, nodular lesions were recognized in 20
      kidneys. Low density nodules were found in three kidneys, isodensity nodules in
      seven, and high density nodules in 10. In a case examined by follow-up five years
      later, the low and isodensity nodules changed to high density nodules with
      decreasing volume. Ultrasound demonstrated the high density nodules as low-echo
      mass lesions. These nodular lesions corresponded with the localized foci in the
      renal parencyma and/or pyocalyx. We consider that the density differences in
      nodular lesions reflect the process of water absorption from the caseous
      necrotizing materials of tuberculosis.

PMID- 7724818
TI  - Intracranial ependymomas: treatment results and prognostic factors.
AB  - Forty-nine intracranial ependymoma patients were postoperatively irradiated with
      craniospinal, cranial, or wide local fields. Thirty-two patients received an
      adjuvant chemotherapy regimen of vincristine and CCNU with or without
      procarbazine. The 10-year actuarial overall and progression-free survival rates
      were 57% and 57%, respectively. Age was the only significant prognostic factor in
      favor of adults (p = 0.01).

PMID- 7724819
TI  - Magnetic resonance imaging of subacute thyroiditis.
AB  - Clinical, laboratory, and scintigraphic findings, and magnetic resonance (MR)
      images of three patients with subacute thyroiditis are presented in all three at
      the time of diagnosis. On T1-weighted images, regions of abnormality with
      irregular margins and slightly high intensity were demonstrated. On T2-weighted
      images, markedly increased intensity was shown in the same sites. On follow-up
      MRI in two patients after treatment, these findings had disappeared or become
      more normal.

PMID- 7724820
TI  - Persistent common bile duct hematoma caused by a small cancer: case report.
AB  - We report a case in which an intrabiliary duct hematoma secondary to a coexisting
      smaller choledochal cancer was observed for more than a month. Initial
      noncontrast enhanced X-ray computed tomography (CT) showed the hematoma as a high
      attenuation mass, leading to the preoperative diagnosis of choledochal stone or
      calcified tumor.

PMID- 7724821
TI  - Right perirenal biloma due to a common bile duct stone: CT demonstration.
AB  - Most reported extrahepatic bilomas have been located around the liver, especially
      in the intraperitoneal cavity. A case of a right perirenal biloma due to a common
      bile duct stone is presented. Intraoperative cholangiography revealed
      extravasation of bile from the branch in the caudate lobe. CT accurately
      demonstrated the fluid around the inferior vena cava and in the right perirenal
      space, which indicated continuity of the liver and right perirenal space.

PMID- 7724822
TI  - Modified Inoue applicator for endometrial brachytherapy.
AB  - The Inoue applicator (3 channels) for endometrial cancer with a microSelectron
      HDR was modified to enable both intrauterine and vaginal treatments to be done at
      the same time. The applicator is described together with a case report.

PMID- 7724823
TI  - Modified ovoid applicator for intracavitary radiation therapy with a Selectron
      MDR or microSelectron-HDR.
AB  - A modified ovoid applicator for intracavitary radiotherapy was developed for
      Japanese and other Asian women. It has more variations of smaller sized ovoids
      than the original rigid standard applicator of the Selectron-MDR and
      microSelectron-HDR. In addition, application of the ovoid pair and tandem flange
      is easy due to the flat surface of the inner aspect of the ovoid pairs, which
      prevents slippage of the ovoids and flange. The applicator is described together
      with source loading and dose distribution.

PMID- 7724825
TI  - Effects and mechanisms of action of endothelins on non-vascular smooth muscle of
      the respiratory, gastrointestinal and urogenital tracts.

PMID- 7724824
TI  - Preoperative diagnosis of the follicular variant of papillary carcinoma of the
      thyroid: discrepancy between image and cytologic diagnoses.
AB  - Preoperative diagnosis of the follicular variant of thyroid papillary carcinoma
      has not been examined sufficiently. The preoperative diagnosis of six patients
      with the follicular variant was investigated retrospectively as compared with 46
      cases of the common type of papillary carcinoma (papillary structure dominant
      type), four of follicular carcinoma, 27 of follicular adenoma, and 42 of
      adenomatous goiter. Cervical soft radiography of the disease exhibited
      calcification in three of six cases (50%), all of which showed coarse
      calcification not accompanied by minute type. 201Tl scintigraphy of the disease
      revealed that four of six cases (66.7%) showed abnormal accumulation in the
      delayed phase. Four cases had favorable washout and one (16.7%) unfavorable
      washout. On ultrasonography, one of six cases (16.7%) was diagnosed as papillary
      carcinoma, four as follicular adenoma, and one as adenomatous goiter. In fine
      needle aspiration cytology, two of five cases were diagnosed as papillary
      carcinoma of class V, two as papillary carcinoma of class IV, and one as
      follicular tumor suspected of class IIIa. On the other hand, true positive
      diagnostic rates of the histological types of tumors other than follicular
      carcinoma by ultrasonography or fine-needle aspiration cytology were
      approximately 80% and relatively satisfactory. Fine-needle aspiration cytology
      was the most useful method of diagnosing the follicular variant of papillary
      carcinoma. It seems necessary to consider the possibility of the follicular
      variant in diagnosis when papillary carcinoma is suspected from fine-needle
      aspiration cytology by preoperative diagnosis, while imaging suggests follicular
      tumor.

PMID- 7724827
TI  - Inhibition of murine peritoneal macrophage functions by sulfated cholecystokinin
      octapeptide.
AB  - The effect in vitro of the sulfated octapeptide form of cholecystokinin, CCK-8,
      at concentrations from 10(-12) M to 10(-6) M on several functions of resting
      peritoneal macrophages from BALB/c mice: adherence to substrate, mobility
      (spontaneous and directed by chemical gradient or chemotaxis), ingestion of inert
      particles (latex beads) or cells (Candida albicans), and production of superoxide
      anion measured by nitroblue tetrazolium reduction was studied. CCK-8, at
      concentrations from 10(-10) M to 10(-8) M, inhibited significantly all functions
      studied with the exception of adherence to substrate, which was increased. A dose
      response relationship was observed, with a maximum inhibition of macrophage
      functions found at 10(-8) M. This neuropeptide induced in murine macrophages a
      significant, but transient, increase of cAMP levels at 60 sec. On the contrary,
      CCK-8 produced a slight but significant decrease of protein kinase C (PKC)
      activity at 5 min of incubation. These results suggest that CCK-8 is a negative
      modulator of several macrophage functions, and that the inhibition of these
      activities is carried out through an increase of intracellular cAMP levels and a
      decrease in PKC activity.

PMID- 7724826
TI  - Expression of pituitary adenylate cyclase activating polypeptide (PACAP) gene by
      rat spermatogenic cells.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) a neuropeptide
      recently isolated from hypothalamus, exists in two biological active forms:
      PACAP38 and PACAP27. The PACAP precursor (preproPACAP) contains besides PACAP a
      29 amino acid peptide designated PACAP related peptide (PRP) in its sequence. The
      hypothalamus has the highest concentration of PACAP, but PACAP mRNA and
      immunoreactivity are found in several other tissues including the testis. Here we
      demonstrate that extracts of testis contain all preproPACAP derived peptides the
      concentrations being: PACAP38 2.8 +/- 0.14 pmol/g wet weight, PACAP27 0.18 +/-
      0.02 pmol/g and PRP 0.84 +/- 0.14 pmol/g, respectively. By in situ hybridization
      PACAP/PRP mRNA was located near the perimeter of the seminiferous tubules in
      early germ cells, and by immunocytochemistry PACAP immunoreactivity was shown in
      spermatids near the lumen, in spermatogonia and primary spermacytes, but not in
      mature spermatids or spermatozoa. The findings suggest that PACAP might be an
      autocrine regulator in developing germ cells during spermatogenesis.

PMID- 7724828
TI  - Specific monoclonal antibodies neutralize the action of PACAP 1-27 or PACAP 1-38
      on intestinal muscle strips in vitro.
AB  - The gut-brain neuropeptide pituitary adenylate cyclase activating polypeptide
      (PACAP) is a novel highly conserved member of the secretin-glucagon-VIP peptide
      family comprising 38 or 27 amino acid residues. In this study, we investigate the
      actions of PACAP 1-27 or PACAP 1-38 on jejunal and caecal muscle strips from pig
      or guinea pig and demonstrate the neutralizing effect of two PACAP-specific
      monoclonal antibodies of the IgG1 subtype, RSP27II and RSP38. These antibodies
      were used to set up assay systems specific for PACAP 1-27 or PACAP 1-38.
      Monoclonal antibody RSP27II recognizes exclusively PACAP 1-27, whereas RSP38
      binds only PACAP 1-38. PACAP 1-27 and PACAP 1-38 relax taenia caeci dose
      dependently in the presence of guanethidine and scopolamine. Both peptides
      inhibit the spontaneous contractions of porcine jejunal muscle strips
      equipotently. Monoclonal antibodies RSP27II and RSP38 specifically neutralize the
      actions of either exogenously applied or endogenously released PACAP. Thus, they
      represent processing-specific tools to examine the physiological role of both
      molecular forms of PACAP in the gastrointestinal tract.

PMID- 7724829
TI  - Developmental expression of transforming growth factor-alpha in the upper
      digestive tract and pancreas of the rat.
AB  - This study was designed to examine the developmental expression and the
      localization of the transforming growth factor alpha (TGF-alpha) in the upper
      gastrointestinal tract and pancreas of the rat. Immunohistochemical techniques
      using an antibody against rat TGF-alpha were performed on the stomach, duodenum
      and pancreas of fetuses (19 to 21 days of gestation), of pups during the suckling
      period (days 0 to 13 postpartum) and after weaning (day 25 postpartum) and of
      adults. The temporal appearance of TGF alpha varied depending on the tissues. In
      the antral mucosa it likely appeared before 19 days of gestation. In this tissue,
      the immunostaining was intense from 20 days of gestation and did not decline
      after birth. In the duodenum, the TGF alpha immunoreactivity was definitely
      present with a high intensity at 20 days of gestation in villi, crypts and
      Brunner's glands and there after became irregular. In the fundic mucosa, TGF
      alpha expression was weak but clearly-established at 21 days of gestation, at
      least in parietal cells, and regularly increased after birth. In the pancreas, it
      appeared only after birth and solely in the exocrine gland. The TGF alpha
      immunoreactivity displayed as age progressed, first a granular pattern apparently
      confined in the supranuclear, i.e., Golgi area, then a diffuse cytoplasmic
      pattern. These findings suggest that TGF alpha may have a functional role during
      the developmental process of the digestive system.

PMID- 7724830
TI  - Purification and amino acid sequence of human motilin isolated from a motilin
      containing liver metastasis.
AB  - The acid extract of a liver metastasis from a patient with elevated plasma
      motilin levels contained large quantities of motilin (3.37 micrograms/ml). The
      extract was concentrated on a C18-column and motilin was isolated by gel
      chromatography (Sephadex G-50) followed by cation ion exchange chromatography
      (HR5/5 Mono-S) and three successive steps of reverse phase chromatography
      (Nucleosil 300-5 C18). The pure peptide was sequenced and the identity of porcine
      and human motilin was confirmed. This is the first report of a tumor containing
      large amounts of motilin.

PMID- 7724832
TI  - Protocols for deriving Canadian water quality guidelines for the protection of
      agricultural water uses. Canadian Council of Ministers of the Environment.

PMID- 7724831
TI  - Comparison between rodent carcinogenicity test results of 44 chemicals and a
      number of predictive systems.
AB  - A comparison is made between a number of predictive systems including bacterial
      mutagenicity, structure alert and chronic toxicity (Tennant et al., 1990),
      COMPACT, Hazardexpert, and DEREK, with the outcome of the two species rodent
      carcinogenicity bioassay for 44 chemicals conducted under the NTP protocol. It is
      shown that, following minor updating of the rodent data in the light of pathology
      reports, there is a generally good agreement between various predictions and the
      actual carcinogenicity results. In particular, a combination of two methods of
      prediction produces an over 80% concordance with the rodent bioassay. Possible
      reasons for various discrepancies are discussed in light of xenobiotic metabolism
      and activation mechanisms of chemical carcinogenesis.

PMID- 7724833
TI  - Interspecies extrapolation in safety evaluation of human medicines in The
      Netherlands (1990-1992): practical considerations.
AB  - Doses used in animal toxicity studies can be extrapolated to therapeutic doses in
      man on the basis of body weight equivalence, metabolism equivalence, or
      toxicokinetics. The validity of extrapolation rules is a matter of debate.
      However, extrapolation on the basis of toxicokinetics is often preferred for
      human medicines, provided that adequate data are available. In registration
      dossiers on human medicines, often insufficient data are available to extrapolate
      on toxicokinetics only. This prompted us to study whether extrapolation on the
      basis of body weight equivalents or metabolism equivalents resembles the
      toxicokinetic way of extrapolation best. A survey was made of new chemical
      entities that have been applied for registration to the Medicines Evaluation
      Board in The Netherlands (College ter Beoordeling van Geneesmiddelen) between
      1990 and 1992. In the majority of cases, larger margins of safety were achieved
      by extrapolation on the basis of body weight equivalents as compared to
      toxicokinetic data. Extrapolation on the basis of metabolism equivalents
      resembled toxicokinetic extrapolation factors better. The method of extrapolation
      using metabolism equivalents was rarely encountered in the registration dossiers
      on human medicines submitted to the Board.

PMID- 7724834
TI  - The EPC approach to estimating safety from exposure to environmental chemicals.
AB  - Reference doses (RfDs) and reference concentrations (RfCs) developed by the
      United States Environmental Protection Agency (USEPA) are typically used in the
      quantitation of risk of potential adverse human health effects from exposure to
      environmental chemicals. For a large number of chemicals, however, USEPA RfDs and
      RfCs have not yet been determined. Thus, for risk assessments that involve a
      large number of chemicals, there is insufficient toxicity information with which
      to evaluate potential adverse human health effects for all chemicals present at a
      particular site. Due to this insufficiency, the risk assessor must either (1)
      ignore potential exposures on the assumption that omitting these exposures does
      not significantly alter decisions concerning the remediation of the site or (2)
      undertake a lengthy and costly analysis to generate the necessary RfDs or RfCs. A
      potential solution to this problem is to develop estimated permissible
      concentrations (EPCs), values which represent permissible environmental
      concentrations or related acceptable daily dosages derived from occupational
      exposure limits. In the present analysis, acceptable daily dosages determined
      using the EPC method were compared to USEPA RfDs or RfCs which were converted to
      dosages based on standard exposure assumptions. Based on a comparative analysis
      of EPCs and USEPA reference values for 103 chemicals, it was found that EPC daily
      dosages represent a reasonably conservative surrogate value when USEPA or state
      reference values are unavailable. Given that there are hundreds of chemicals with
      occupational exposure limits but no state or USEPA reference values, acceptance
      of the EPC methodology would provide an interim solution for the problem of
      insufficient toxicity information for a substantial number of environmental
      chemical contaminants.

PMID- 7724835
TI  - The rodent carcinogenicity bioassay produces a similar frequency of tumor
      increases and decreases: implications for risk assessment.
AB  - We examined the overall results of 124 consecutive rodent carcinogenesis assays
      carried out at the maximum tolerated dose on 37 chemicals reported recently by
      the Toxicology Program of the United States. In 31 experiments each in male and
      female F-344 rats and in male and female B6C3F1 mice, tumor increases and
      decreases occurred in 41 and 46% of the experiments, respectively. In 22
      experiments both increases and decreases in tumor incidence were reported. Of the
      experiments with decreases in tumor incidence, about 70% were associated with
      lower body weights of the treated animals. However, of the 30 chemicals producing
      some tumor decreases, 12 showed decreases in some experiments without any
      association with bodyweight. Ten chemicals that were Salmonella positive produced
      increases and decreases in tumor incidences and three produced only decreases in
      tumor incidence. If it is considered that the bioassay provides information
      relevant to the carcinogenic potential of a chemical, then logically it must also
      be considered that information about the cancer-preventive potential of a
      chemical is provided. When a chemical causes increases and decreases in tumors,
      several questions follow. First, which are more relevant to the health of an
      exposed individual: tumor increases or tumor decreases? Second, should such a
      chemical be stigmatized as a "carcinogen," in view of all the legal and economic
      implications that ensue from such a label? Third, how should one define a
      carcinogen?

PMID- 7724837
TI  - International harmonization for the risk assessment of pesticides: results of an
      IPCS survey.
AB  - Risk assessment harmonization has become an important issue on the environmental
      agendas of numerous countries. The benefits of an international consensus on risk
      assessment methodologies include decreased duplication of toxicity testing
      through the sharing of experimental data, decreased barriers to trade, and more
      consistency and cooperation within the scientific community. This paper presents
      the findings of an international survey of regulatory scientists in OECD and
      select non-OECD countries. The survey was sponsored by the International
      Programme on Chemical Safety (IPCS), which itself was formed by a cooperative
      agreement between the World Health Organization, the International Labor
      Organization, and the United Nations Environment Program. The survey results
      represent the first step in a project initiated by the IPCS to harmonize risk
      assessment methodologies used worldwide for the toxicological evaluation of
      chemicals. In this phase, the primary focus was on the health risk assessment of
      pesticides. Participants responded to questions regarding: (1) the support or
      review documents relied on for performing risk assessments; (2) procedures used
      and criteria applied when evaluating carcinogenicity data, including issues
      relating to mechanism of action, the maximum tolerated dose, and doses used in
      carcinogenicity bioassays; (3) risk assessment methodologies, such as the use no
      effect levels with safety factors or risk assessment models; (4) methods for
      assessing occupational and dietary exposure to pesticides; and (5) the primary
      areas of interest for the commencement of international harmonization efforts.
      There was significant consensus on specific issues relating to risk assessment
      methods and carcinogenicity assessment, as well as strong positive support for
      international harmonization activities. Differences existed with respect to the
      doses used in bioassays and data interpretation.

PMID- 7724838
TI  - Dichlorvos carcinogenicity: an assessment of the weight of experimental evidence.
AB  - After 30 years of experience with human exposure to dichlorvos (DDVP) in the
      home, workplace, and sickroom, the U.S. EPA has published its intent to revoke
      the food additive registration of this cholinesterase-inhibiting insecticide. The
      basis for the Agency action is the result of the National Toxicology Program
      (NTP) toxicology and carcinogenesis study of DDVP in rats and mice (NTP Technical
      Report No. 342, September 1989). In those experiments the NTP considered the
      result in the female mouse portion of the study to afford unequivocal evidence of
      carcinogenicity. The NTP considered the interpretations of the male and female
      rat and the male mouse studies to be less than clear. Despite the NTP
      interpretation, the EPA considers the male rat data (increased incidence of
      mononuclear cell leukemia) to be sufficient to warrant the regulatory change. The
      purpose of this report is to summarize a review of the interpretation of the NTP
      data and to assess the predictive validity of the results relative to potential
      human health impact. Critical review of experimental data indicates that the
      evidence for a carcinogenic effect of DDVP in animals is equivocal. Further, DDVP
      possess no in vivo mutagenic activity in mammalian assay systems and it bears no
      significant structural similarity to known carcinogens. Therefore, a weight-of
      the-evidence analysis leads to the conclusion that DDVP poses neither mutagenic
      nor carcinogenic risks to humans exposed under normal conditions of use of
      foreseeable conditions of misuse.

PMID- 7724836
TI  - Carcinogen risk assessment: international comparison.
AB  - This report compares carcinogen risk assessment methodologies used by various
      countries as a basis for regulatory actions. The methodologies are based on
      scientific analysis, but national governments have used different approaches for
      dealing with uncertainties in the analysis. Both scientific judgment and social
      policy play a role in resolving scientific uncertainties. Since risk assessment
      methodologies, and subsequent regulatory policies, ultimately impact world trade,
      efforts to harmonize approaches to risk assessment are important. This paper
      represents an effort to understand current approaches to carcinogen risk
      assessment as a first step toward harmonization.

PMID- 7724839
TI  - A comparison of liver tumor diagnoses from seven PCB studies in rats.
AB  - Through a policy assumption, all polychlorinated biphenyls (PCBs) are considered
      probable human carcinogens by most regulatory agencies based on experimental
      studies in rodents where an increased incidence of liver tumors has been
      observed. Recognizing that new consensus criteria for the diagnoses of liver
      tumors in rats had been promulgated, a reevaluation of liver tumor diagnoses from
      seven PCB studies in rats was undertaken. These seven studies, in which rats were
      fed PCB mixtures containing 42, 54, or 60% chlorine, were considered to be the
      best studies from which to evaluate the cancer potential of PCB mixtures. The
      reevaluation results, where consistent diagnoses now exist across all studies,
      clearly indicate major differences in carcinogenic potential based on degree of
      chlorination. Studies of mixtures with 60% chlorination consistently resulted in
      a high incidence of liver tumors, whereas studies in which rats were fed mixtures
      with 54 or 42% chlorination showed no statistically significant increases in
      liver tumors. These data indicate that continuation of a science policy of
      assuming that all PCBs are probable human carcinogens with a potency equivalent
      to the mixture that contains 60% chlorine has no scientific foundation and should
      be reconsidered.

PMID- 7724842
TI  - Role of fiber dissolution in biological activity in rats.
AB  - This report deals with the role of dissolution in removing long fibers from the
      lung and with a mathematical model that predicts chronic effects in rats
      following inhalation or intraperitoneal (i.p.) injection of fibers. Results of
      intratracheal instillation studies and inhalation studies in rats demonstrate
      clearly that long vitreous fibers dissolve in vivo at about the same rate
      measured in vitro in fluid designed to stimulate the extracellular lung fluid.
      For the glass, rock, and slag wool fibers tested, dissolution removed most of the
      fibers longer than 20 microns inhaled into the rats' lungs within 6 months after
      both short-term (5 days) and long-term (1 to 2 years) exposures. A mathematical
      model was developed that is based on fiber dissolution and allows one to predict
      the development of chronic lung diseases in rats. The model predicted the
      incidence of fibrosis and lung tumors in a series of recent inhalation studies
      and tumors following ip injection to within about the error of the experiments.
      The model suggests that all fibers, regardless of their dissolution rate in lung
      fluid, can produce tumors after ip injection because the dose can be unlimited by
      this route. After inhalation, in contrast, dissolution of many types of long
      vitreous fibers occurs rapidly, and disease does not ensue for these fibers.

PMID- 7724841
TI  - Proceedings of Symposium on Synthetic Vitreous Fibers: Scientific and Public
      Policy Issues. Arlington, Virginia, March 2-3, 1994.

PMID- 7724840
TI  - The Delaney debate is losing focus.

PMID- 7724843
TI  - A review of some biophysical factors and their potential roles in the development
      of fiber toxicity.

PMID- 7724844
TI  - Assessing health risks of synthetic vitreous fibers: an integrative approach.
AB  - This paper reviews a tiered approach to acquiring information from multiple
      experimental systems to understand and assess the potential human health risks of
      exposure to airborne synthetic fibers. The approach is grounded in the now widely
      accepted research-risk assessment-risk management paradigm. It involves the
      acquisition of information that will provide mechanistic linkages within the
      exposure-dose-response paradigm. It advocates the use of the inhalation route of
      exposure for developing relevant information for assessing human health risks and
      calls attention to serious problems encountered using nonphysiologic routes of
      administration to assess human health risks.

PMID- 7724845
TI  - Default assumptions in carcinogen risk assessment used by regulatory agencies.
AB  - Uncertain components in carcinogen risk assessment are bridged in different ways
      in various regulatory agencies, depending on the goal of risk assessment. The
      U.S. EPA's goal in carcinogen risk assessment is to derive an estimate of the
      upper bound to risk. Generic default assumptions, designed to obtain a plausible
      upper bound to risk, are used to bridge uncertain components. The EC, and several
      member countries, seek estimates of the incidence of cancer likely to occur in
      the human population. Little or no use is made of genetic default assumptions.
      Uncertain elements of risk assessment are handled on a case-by-case basis,
      applying scientific judgement in light of the data available for each individual
      substance.

PMID- 7724846
TI  - A commentary on the NRC report "Science and judgment in risk assessment".
AB  - This article provides a brief overview of the report "Science and Judgment in
      Risk Assessment," prepared by a Committee of the National Research
      Council/National Academy of Science in response to a U.S. Environmental
      Protection Agency request mandated by the Clean Air Act Amendments of 1990 (CAAA
      1990). The report critiques EPA's current approaches for characterizing human
      cancer risks from exposure to chemicals and offers recommendations for the
      conduct of future cancer risk assessments, especially those required in
      implementing the CAAA-1990 provisions which are concerned with hazardous air
      pollutants. The report offers specific recommendations that address the role of
      default options, data needs, methods and models, uncertainty, variability, and
      the aggregation of data. A cross-cutting theme of the report is the use of an
      iterative approach in which screening assessments with limited data and, of
      necessity, default options used in the absence of specific scientific data may be
      performed initially followed by subsequent assessments, as needed, in which
      increasing amounts of data are developed and incorporated. In some instances, the
      specific data on a given chemical or pollutant source will replace conservative
      default options used in earlier assignments. The report includes two authored
      appendices that address issues related to the use of default options and their
      replacement by specific scientific information. One appendix by Finkel advocates
      a principle of "plausible conservatism" for choosing and altering default options
      and in making cancer risk estimates. A second appendix by McClellan and North
      advocates the full use of scientific information in the risk assessment process.
      This article gives major attention to the key aspects of the NRC/NAS report,
      especially those dealing with the use and replacement of default options. The
      default options and the extent to which the options are replaced with specific
      science have major impact on the final quantitation of cancer risk for exposure
      to chemicals.

PMID- 7724847
TI  - Health risk assessment research: implications for synthetic vitreous fibers.
AB  - While synthetic vitreous fibers (SVFs) are thought responsible for respiratory
      illnesses, more research is needed to understand the nature of exposure. Much of
      the research necessary to evaluate the risk of the possible health effects to
      humans will be supported by the U.S. Federal Government, either specifically to
      elucidate the effects from exposure to SVFs, or more generally to improve the
      process of risk assessment. In this context, the Office of Technology Assessment
      (OTA) examined the Federal research activities to improve risk assessment, with a
      focus on current activities and the funding and management of that research. OTA
      defined risk assessment research as research designed to improve the process of
      health risk assessment or chemical-specific risk estimates. OTA found that risk
      assessment is not a national research priority. Environmental health research
      funding has neither kept up with increases in health research nor with increases
      in environmental mandates that depend on that research for decision making. OTA
      finds the need to stress the interdependency and the linkage of the various
      research activities, risk assessment, and policy making. Finally, the exploration
      of many promising areas for research requires linkages not only among various
      scientific disciplines but also with decision makers.

PMID- 7724848
TI  - Carcinogenicity assessment of synthetic vitreous fibers--international regulatory
      perspective.

PMID- 7724849
TI  - International lists and regulatory reactions: good science needed.

PMID- 7724851
TI  - A multiyear workplace-monitoring program for refractory ceramic fibers.
AB  - This paper summarizes interim results of a 5-year workplace monitoring program
      conducted by firms belonging to the Refractory Ceramic Fibers Coalition (RCFC)
      pursuant to a Consent Agreement with the U.S. EPA. The exposure monitoring
      program is part of a model Product Stewardship Program (PSP) developed by RCFC.
      This paper reviews the refractory ceramic fiber (RCF) industry, findings of
      animal bioassay and epidemiological investigations, and the regulatory approach
      used by EPA. The scope, protocols, sample collection budgets, and experimental
      design of the monitoring program are summarized. In brief, the program will
      gather 720 time-weighted average (TWA) workplace concentration measurements
      annually, partitioned among 8 functional job classifications, both from plants
      that manufacture and from those that process or use RCF. Statistical analyses
      reveal that: workplace airborne RCF concentration data are approximately log
      normally distributed, 93% of workplace TWAs are beneath the industry's
      recommended exposure guideline of 1 fiber per cubic centimeter (f/cc), there are
      significant differences in average workplace RCF concentrations among job types,
      and PSP activities are effective in lowering workplace exposure. Results of this
      effort provide an interesting illustration of a successful cooperative effort
      between a responsible industry and regulatory agencies.

PMID- 7724850
TI  - Science, public policy, and stewardship.
AB  - Synthetic vitreous fibers play an important role in today's economy. Glass
      fibers, as an example, have found uses in more than 30,000 products that include
      insulations, reinforcements, fire resistant fabrics, and protective armor.
      Vitreous fibers also play a direct role in energy conservation. For example, in
      1992, a study by Arthur D. Little found that the annual production of fiber glass
      batts and blowing wool used in U.S. buildings--only a fraction of the current
      production and use of glass wool--saved the equivalent of 33.4 million barrels of
      oil in 1992, avoiding the need for nearly 6800 megawatts of power. This is
      equivalent to 34 new 200-megawatt power plants. An ongoing commitment by the
      manufacturers to assure the safety of their products paralleled the growth of the
      vitreous fiber industry. Soon after commercialization of glass wool manufacturing
      in the mid-1930s, worker concerns about silica gave rise to the first study on
      the health of fiber glass workers (Siebert, 1942). Since that time, there have
      been hundreds of studies, published papers, and international reviews that have
      evaluated potential health effects and exposures associated with synthetic
      vitreous fibers.

PMID- 7724852
TI  - Postscript: science and public policy on synthetic vitreous fibers.
AB  - Rapid advances are being made in our understanding of the interaction of airborne
      fibers with biological tissues. It is possible to reduce human exposures and
      potential risk to lung cancer and fibrosis if current science and models are
      fully utilized. However, the criteria used by IARC and NTP in their cancer
      classifications have not kept pace with current science and, in fact, remain
      entrenched in the scientific vagaries present in the 1960's. As long as public
      policy cannot keep pace with contemporary scientific understanding, we are doomed
      to a world of exaggerated risks, inappropriate regulations, misguided priorities,
      inadequate funding for social and environmental programs, mass anxiety, and
      skepticism about scientific research.

PMID- 7724853
TI  - Synthetic vitreous fibers--inhalation studies.
AB  - Synthetic vitreous fibers (SVFs), often referred to as "man-made vitreous
      fibers," are a class of materials that have their major uses for insulation
      against heat and sound. The original fibers are produced by melting various types
      of rock, clay, etc. and then blowing or extruding them into fibers of particular
      properties. During production and use small fractions of airborne fibers can be
      generated. Because of this a series of state-of-the-art inhalation studies was
      initiated to study the possible health hazards presented by the four major types
      of vitreous materials [two types of insulation glass wool, rock wool, slag wool,
      and four types of refractory ceramic fibers (RCF)] found in the workplace or to
      which the general public may be exposed. Rats and hamsters (30 mg/m3 kaolin-based
      RCF only) were exposed by nose-only inhalation to 3, 16, or 30 mg/m3 for 6
      hr/day, 5 days/week, for 18 (hamsters) or 24 (rats) months and were held for
      lifetime observation (until approximately 20% survival) to study the chronic
      toxicity and potential carcinogenic activity of these classes of SVFs. Chrysotile
      or crocidolite asbestos served as positive controls. All of the fibers stimulated
      an inflammatory response characterized by an increase in the number of pulmonary
      macrophages at the level of the terminal bronchioles and proximal alveoli. RCF
      produced interstitial fibrosis in the walls of the proximal alveoli as early as 3
      months and rock wool by 12 months. The only fiber which showed carcinogenic
      activity was RCF which produced a dose-related increase in both primary lung
      neoplasms (rats only) and mesotheliomas (rats and hamsters).

PMID- 7724854
TI  - A comparison of human exposures to fiberglass with those used in a recent rat
      chronic inhalation study.
AB  - In a recent rat inhalation study, 2 years of exposure to high concentrations of
      fiberglass (FG) resulted in no treatment-related fibrosis or thoracic tumors. To
      determine the relevancy of this study for human risk assessment, it is important
      to compare the rat experimental exposure levels with those of humans. Data on
      human exposures were taken from several studies and included FG manufacturing,
      installation and removal, and ambient air. FG levels in the rat aerosol were
      200,000-fold higher than indoor air, > 2000-fold higher than during FG insulation
      manufacturing, and > 1000-fold higher than FG batt installation. The rat aerosol
      was 30-fold more concentrated than the highest human exposure (blowing
      installation of unbound FG). Rat FG lung burden also vastly exceeded that of FG
      workers, which was not significantly elevated above nonworker levels. The amount
      of fibers/mg dry lung for the rat after lifetime exposure was > 4000-fold greater
      than for the FG worker, average exposure 11 years. Aerosol and lung fiber
      dimensions in the rat study were comparable to those of human exposures. From
      these comparisons, it can be concluded that the exposure level in the rat
      inhalation study was sufficiently, if not excessively, high in comparison to
      human exposures. Increasing the experimental exposure in the rat studies would
      not serve to mirror human environmental or occupational exposures.

PMID- 7724856
TI  - Epidemiology studies of synthetic vitreous fibers: methods used and current
      studies.
AB  - Epidemiologic designs (case control, cohort, and surveillance) and measures of
      association are discussed in the context of studies in the Synthetic Vitreous
      Fibers industry. Current investigations including a case control study for Owens
      Corning's Newark, Ohio plant and a Corporate-wide Mortality Surveillance System
      are described. The importance of internal validity and the need to account for
      confounding are demonstrated. Estimates of the prevalence of smoking developed
      for the Newark plant and the U.S. population have been used to adjust a
      previously reported statistically significant lung cancer Standardized Mortality
      Ratio (SMR) for Owens-Corning's Newark plant. After adjusting for the confounding
      effect of cigarette smoking, the Newark SMR based on national mortality rates is
      reduced to a statistically insignificant 107.7, a level quite similar to that
      obtained using local mortality rates. While smoking does not account for all of
      the excess lung cancer mortality in this population compared to U.S. mortality,
      these investigations make it clear that plant exposures including respirable
      glass fibers are not responsible for the remaining excess; rather, this excess
      reflects the effect of some unknown set of social, demographic, or chance
      factors.

PMID- 7724855
TI  - World health organization (WHO) consensus questionnaire on validity of methods
      for assessment of carcinogenicity of man-made fibers.
AB  - In May 1992, the WHO European Office held an expert consultation on the
      assessment of carcinogenicity of man-made fibers. WHO decided to determine
      whether the conclusions of such an expert consultation would be supported by
      scientific opinion internationally. For this experiment, WHO sent the 28
      conclusions of the consultation, as a Consensus Questionnaire, to scientists
      worldwide seeking agreement, or otherwise, with the conclusions. Two hundred
      scientists responded. For every conclusion, at least 70% of respondents agreed,
      and for over half the conclusions more than 90% agreed. For some conclusions
      there were significant differences by country of respondent and/or by work
      environment. Respondents from the U.S.A., or in Government employ, tended to
      agree with the questions less often, and those from Germany, or from Industry,
      most often. The disagreements were most often related to questions concerned with
      the models for assessing carcinogenicity, but in every case the disagreements
      were expressed by fewer than one in three of respondents. There was minority
      opinion that the inhalation model was not adequately sensitive for assessing
      human hazards and that the intraperitoneal test could give validated answers on
      the carcinogenicity of fibers. Three questions demonstrated significant
      variability in response rate both from country to country and by work environment
      group. Each of the original WHO conclusions was concerned with shortcomings of
      the intraperitoneal test, when used for carcinogenicity classification. For these
      questions, the overall agreement rates were 85 to 91%. Respondents from U.S.A.
      and from Government disagreed with the WHO conclusions more often than others.
      Those from Germany and in Research agreed most often. This experiment has shown
      that the Consensus Questionnaire approach can be used to seek international
      scientific opinion. It has also shown that the conclusions of future expert
      consultations need to be formulated in a manner suitable for the Consensus
      Questionnaire approach, to avoid the ambiguities that can arise if too many
      concepts are included within a single conclusion.

PMID- 7724857
TI  - Mechanisms of fiber-induced diseases: implications for the safety evaluation of
      synthetic vitreous fibers.
AB  - Inhalation of certain natural mineral fibers, such as amphibole asbestos, is
      associated with the development of inflammatory, fibroproliferative, and
      neoplastic diseases in the lung and pleura of man and experimental animals. The
      mechanisms by which fibers induce fibrosis and cancer are largely unknown, but
      are thought to be modulated by reactive oxygen species and altered growth factor
      pathways. Studies in rats using intracavitary implantation and instillation of
      fiber preparations led to the belief that all fibers with certain dimensional
      characteristics had similar toxic potential. It is now known that different fiber
      types of similar dimension can vary substantially in biological activity. A
      variety of physicochemical properties govern fiber toxicity and carcinogenicity,
      including: size and shape; surface chemistry; solubility and biopersistence; and
      chemical composition. Although the molecular event(s) that translate fiber
      induced cellular injury into a pathologic state are unknown, there is strong
      evidence in man and laboratory animals to suggest both dose dependency and
      thresholds for effects.

PMID- 7724858
TI  - An overview of animal models for assessing synthetic vitreous fibers (SVFs)
      safety.
AB  - Synthetic vitreous fibers (SVFs) are materials with many important commercial
      applications. The fibrous nature of the SVFs raises concerns about their
      potential human health hazards. However, sufficient epidemiological data do not
      exist to establish the hazardous nature of all SVFs. In addition, the cellular
      and molecular mechanisms underlying the induction of pulmonary lesions are only
      partially understood. Without sufficient evidence to associate fiber exposure and
      lung disease, animal bioassays have been used to identify specific hazardous
      fibers. These bioassays include inhalation exposures, intratracheal instillation,
      and intracavitary injection (intrapleural and intraperitoneal). Inhalation
      exposures of animals most closely represent the human experience, but these
      exposures are costly and time-consuming to conduct. Intratracheal and
      intracavitary administrations of fiber are alternatives to inhalation exposures;
      however, they do not represent human exposures and can give false positive
      results. The limitations of the noninhalation approaches must be considered when
      addressing the potential for a respirable fiber to induce human lung disease. In
      addition, when the results from inhalation exposures do not agree with the
      alternative animal assays, most weight should be given to the animal inhalation
      assays because of the limitations of the alternative approaches. To determine the
      safety of SVFs, both the inhalation and noninhalation approaches are suggested.

PMID- 7724859
TI  - Measurement of respirable glass and total fiber concentrations in the ambient air
      around a fiberglass wool manufacturing facility and a rural area.
AB  - Little data are available on ambient concentrations of glass fibers which along
      with other manmade vitreous fibers are receiving increased regulatory attention.
      The purpose of this study was to measure glass and total respirable fibers around
      a large fiberglass wool manufacturing plant and a rural area. Samples were
      collected on mixed esters of cellulose filters using high-volume air samplers at
      flow rates of 1.2 m3/min. Fibers were counted using a modified NIOSH 7400B
      procedure. Glass fibers were found in very low concentrations for both areas
      sampled; 90% of the samples were below the detectable limit of 0.00001 fibers/cc.
      Average glass fiber concentrations accounted for less than 1% of the total fibers
      measured. Dispersion modeling was used to estimate ambient glass fiber
      concentrations around the plant. Predicted and measured results showed relatively
      good agreement.

PMID- 7724860
TI  - The behavior of glass fibers in the rat following intraperitoneal injection.
AB  - Potential carcinogenicity of fibers is believed to be determined by three
      factors: the dose, dimensions and durability of the fibers concerned. Currently
      there is considerable debate on the appropriateness of using results from
      intraperitoneal (i.p.) injection studies to predict the potential carcinogenicity
      of airborne fibers following inhalation. For ip results to have any significance
      to potential inhalation hazards, there should be some relation between the
      biopersistence, dose, and dose distribution of fibers in the serosal cavity and
      in the lung. Preliminary results on the durability of one experimental glass
      fiber in the peritoneal cavity suggest differences in dissolution when compared
      with durability in the lung. In the lung, the diameters of the long fibers (> 20
      microns) were observed to decline at a rate consistent with their exposure to a
      neutral pH environment. The diameter of shorter fibers declined much more slowly,
      consistent with exposure to a more acidic environment such as is found in the
      phagolysosomes of alveolar macrophages. In the peritoneal cavity all fibers,
      regardless of length, dissolved at the same rate as short fibers in the lung. The
      effect of dose on the distribution of fibers in the peritoneal cavity was
      investigated using similar experimental glass fibers and compared with that of a
      powder made from ground fibers. For both materials at doses up to 1.5 mg,
      material was taken up by the peritoneal organs roughly in proportion to their
      surface area. This uptake was complete 1-2 days after injection. At higher doses,
      the majority of the material in excess of this 1.5 mg formed clumps of fibers
      (nodules) which were either free in the peritoneal cavity or loosely bound to
      peritoneal organs. These nodules displayed classic foreign body reactions with an
      associated granulomatous inflammatory response. The findings on both durability
      in the peritoneal cavity and the presence of two distinct populations of material
      following i.p. injection have implications for the justification of the use of
      i.p. injections to assess potential carcinogenicity of fibers following
      inhalation.

PMID- 7724861
TI  - Peptic ulcer: psychosomatic or infectious disease? Etiologic factors revisited
      ten years after the Campylobacter-helicobacter advent.

PMID- 7724862
TI  - Cardiac plexus of dogs experimentally infected with Trypanosoma cruzi:
      inflammatory lesions and quantitative studies.
AB  - Qualitative and quantitative aspects of the superficial and profound cardiac
      plexus of dogs experimentally infected with Be-62 and Be-78 strains of
      Trypanosoma cruzi were studied. Animals were autopsied in the acute phase of
      infection. The inflammatory process, lesions and number of parasites were more
      intense and frequent in animals infected with the Be-78 strain than in those
      infected with Be-62. Despite this, no statistically significant differences could
      be found between the number of neuron bodies in the ganglia of infected and
      control dogs.

PMID- 7724863
TI  - Evaluation of platelet number and function and fibrinogen level in patients
      bitten by snakes of the Bothrops genus.
AB  - Platelet function and plasma fibrinogen levels were evaluated in 14 patients, 10
      males and 4 females, aged 13-59 years bitten by Bothrops genus snakes. There was
      a statistical difference (p < 0.05) among plasma fibrinogen levels evaluated 24
      and 48 hours after envenomation. There was a tendency towards normalization after
      48 hours of treatment. The low platelet number was clear in 24-48 hour
      evaluations with a tendency towards normalization after 48 hours of treatment (p
      < 0.05). When platelet function was stimulated by collagen and epinephrine, it
      appeared to be within normal values. On the other hand, when it was stimulated by
      adenosine diphosphate (ADP), platelet function was hypoaggregated by a single
      micromol concentration until 48 hours after treatment. At a 3 micromol
      concentration, there were alterations only before specific treatment (p < 0.05).
      Fibrinogen levels and fibrin degradation product (FDP) levels appeared to be
      altered in 83.33% of patients evaluated. The authors suggest that platelet
      hypoaggregation is related to decreased fibrinogen and increased FDP levels.

PMID- 7724864
TI  - [Prevalence and epidemiolgic aspects of giardiasis in day care centers in the
      Municipality of Aracaju, SE, Brazil].
AB  - A survey of the giardiasis prevalence was done in children from 2 till 5 years
      old who frequented two day nurseries ("A" and "B"). Its relation with some
      epidemiological aspects through the realization of parasitological exams of stool
      and an inquiry applied to mothers. In day nursery "A" with a high standard a
      life, 20 (66.6%) of 30 inquired children were parasitised and all the children in
      day nursery "B" had some enteroparasite. Giardia lambia was found in 15 (50%) of
      the children in better standard of life and in 19 (63.3%) of the children with a
      lower one. The ingesting of vegetables was the only allied factor to the high
      degree of giardiasis in day nursery "A". The day nursery "B" suffered influences
      from other aspects: no potable water in the residences, the inappropriate destiny
      of the garbage, the ingesting of vegetables habit and collective bedroom. The
      adequate sanitation and the existence of domestic animals were not related to
      parasitism by Giardia lamblia.

PMID- 7724866
TI  - [Congenital Chagas in Bolivia: comparative study of the effectiveness and cost of
      diagnostic methods].
AB  - Eight hundred and twenty newborn babies with a mean weight of < or = 2500g from
      the Maternity Hospital P Boland in Santa Cruz- Bolivia were examined in 1988-1989
      by different methods to diagnose Chagas disease, (placental pathology, serology,
      parasitologically and clinically) to determine the efficiency and cost of these
      methods. The histopathological exam detected 87 cases of placenta infection. Out
      of this total 43 (49%) newborns were positive on the parasitological exam of the
      chord blood. This number increased by repeating the blood test during the first
      month of the baby's life, reaching the same level as the histopathology. With the
      serology, only 2 cases were detected as positive. The clinical sign with a high
      specificity in children infected with Chagas disease is the hepatosplenomegaly.
      The advantages and disadvantages regarding the cost and feasibilty of two
      strategies to detect congenital Chagas disease are being discussed. The first in
      based on the histopathology and the other over on parasitology. It is concluded
      that the control programs for this non vectorial form of Chagas' disease cannot
      be uniform since the aspects to consider are: prevalence of the disease,
      existence of the vector and availability to laboratory techniques.

PMID- 7724865
TI  - [Frequency of intestinal helminth eggs in public restrooms in Sorocaba, SP].
AB  - Four hundred and five water closets were investigated: 11 located at public
      squares, 2 at the railroad station, 4 at the bus station, 55 at bars and
      restaurants, 146 at state schools, 116 at municipal schools, 8 at private
      schools, 36 at public health centers, 16 at sports centers, 8 at orphanages and 3
      at shopping malls. Microscopy slides with adhesive tape were used. The material
      was obtained by sticking the tape onto the following elements: 4 spots on the
      toilet seat, internal and external door knobs, latch, faucet handle and discharge
      valve (push button or pulling string). Out of the 405 water closets studied, 22
      (5.43%) were contaminated. Eggs of Ascaris lumbricoides, Ancylostomatidae,
      Enterobius vermiculares, Taenia sp and Hymenolepis nana were found. In 2 water
      closets eggs of 2 parasites were found simultaneously.

PMID- 7724867
TI  - Spontaneous regional healing of extensive skin lesions in diffuse cutaneous
      Leishmaniasis (DCL).
AB  - The authors report a case of diffuse cutaneous leishmaniasis, with longstanding
      evolution and presenting with diffuse infiltrated lesions rich in amastigotes in
      the absence of mucosal involvement. In situ characterization with monoclonal
      antibodies revealed Leishmania amazonensis. Large regional lesions have presented
      spontaneous healing without specific therapy. Considering that DCL presents with
      a defect in the cellular immune response, this fact demonstrate that this patient
      may develop a regional cellular immune response enough to destroy the parasites
      and to produce clearing of some lesions.

PMID- 7724868
TI  - [The coconut babacu (Orbignya phalerata martins) as a probable risk of human
      infection by the agent of chromoblastomycosis in the State of Maranhao, Brazil].
AB  - During a survey of 30 patients with chromoblastomycosis followed at the Hospital
      dos Servidores do Estado do Maranhao, the authors observed in 2 (6.6%) patients
      with lesions on the buttock. This is an uncommon site for the initial lesions of
      chromoblastomycosis. There is often a history of microtraumatism during the
      farming job hence the more frequent development of lesions in the lower limbs.
      Both patients had 10 years disease, with the presence of nodules and vegetant
      warty lesions in coalescent plaques on the right buttock. Etiologic diagnosis
      made through histopatologic and culture exams, with Fonsecaea pedrosoi isolated.
      The epidemiological exposure of the patients, was suggested by the fact that both
      worked as babacu coconut cutters a common activity in Maranhao State. The
      relation between this kind of professional activity and the development of
      infection merits for the investigation.

PMID- 7724869
TI  - No change in one biological parameter for Dipetalogaster maximus after 20 years
      of laboratory colonisation.

PMID- 7724870
TI  - [Bone alterations observed in diffuse cutaneous leishmaniasis in the State of
      Maranhao].

PMID- 7724872
TI  - [Acute respiratory disease caused by Hantavirus Four Corners].

PMID- 7724873
TI  - Effects of water deprivation on renal hydroelectrolytic excretion in chronically
      Trypanosoma cruzi-infected rats.
AB  - The effect of an 8 hour-period of water deprivation on fluid and electrolyte
      renal excretion was investigated in male Wistar rats infected with the strain Sao
      Felipe (12SF) of Trypanosoma cruzi, in comparison with age and sex matched non
      infected controls. The median percent reductions in the urinary flow (-40% v-63%)
      and excretion of sodium (-57% v -79%) were smaller in chagasic than in control
      rats, respectively. So, chagasic rats excreted more than controls. On the other
      hand, the median percent decrement in the clearance of creatinine was higher in
      chagasic (-51%) than in controls (-39%). Thus, chagasic rats showed some
      disturbed renal hydroelectrolytic responses to water deprivation, expressed by
      smaller conservation, or higher excretion of water and sodium in association with
      smaller glomerular filtration rate. This fact denoted an elevation in the
      fractional excretion of sodium and water.

PMID- 7724871
TI  - [Total length of 2 populations of Dipetalogaster maximus].

PMID- 7724875
TI  - Bioeffects of weak electromagnetic fields.
AB  - Time varying magnetic fields are most often employed for therapeutic purposes and
      are present in environmental sources. In order for an electromagnetic field
      bioeffect to be possible, the signal parameters should not only satisfy the
      dielectric properties of the target, but also induce sufficient voltage to be
      detectable above thermal noise. The problem of the sensitivity of living cells
      and tissues is discussed in relation to signal/noise ratio at the target site.
      Some biophysical models for interactions of weak electromagnetic fields with
      biological systems are summarized. Cell studies and therapeutic application of
      electric and magnetic fields indicate that weak electromagnetic fields can have a
      profound effect on a large variety of biological systems.

PMID- 7724874
TI  - An outline on electromagnetic radiation and public health.

PMID- 7724876
TI  - Melatonin suppression by static and extremely low frequency electromagnetic
      fields: relationship to the reported increased incidence of cancer.
AB  - An increased cancer incidence has been reported in individuals living and/or
      working in an environment in which they are exposed to higher than normal
      artificial electromagnetic fields. One of the most uniform changes associated
      with the exposure of animals to either pulsed static geomagnetic fields or to
      sinusoidal extremely low frequency magnetic fields has been a reduction in high
      night-time levels of melatonin. Melatonin is a hormone produced especially at
      night in the pineal gland, a pea-sized organ near the center of the human brain.
      The high nocturnal production of melatonin leads to elevated blood melatonin
      levels at night as well. The exposure of humans or animals to light (visible
      electromagnetic radiation) at night rapidly depresses pineal melatonin production
      and blood melatonin levels. Likewise, the exposure of animals to various pulsed
      static and extremely low frequency magnetic fields also reduces melatonin levels.
      Melatonin is a potent oncostatic agent and it prevents both the initiation and
      promotion of cancer. Reduction of melatonin, at night, by any means, increases
      cells' vulnerability to alteration by carcinogenic agents. Thus, if in fact
      artificial electromagnetic field exposure increases the incidence of cancer in
      humans, a plausible mechanism could involve a reduction in melatonin which is the
      consequence of such exposures.

PMID- 7724877
TI  - Assessment of exposure to EMF in a Danish case-control study of childhood cancer.
AB  - In Denmark it is permitted to draw overhead lines across residential areas. In
      connection with a Danish case-control study we developed a method for estimating
      the historical values of magnetic fields at residences. The study included 1,707
      cases with childhood cancer and 4,788 matched population controls. A total of
      16,082 different addresses had been occupied by the families from the time of
      conception until the date of diagnosis. The values of the extreme, maximum,
      middle and minimum 50 Hz magnetic field strengths originating from a 50-400 kV
      high-voltage installation were estimated for each of the dwellings included in a
      potential exposure area. 30 children were exposed to an average level of magnetic
      fields of 0.1 microT or more. The evaluated Danish method of exposure assessment
      was compared with the method for residential wiring codes developed by Wertheimer
      and Leeper /1/. We concluded that the US wiring codes are inappropriate for use
      in connection with the Danish electricity transmission system.

PMID- 7724878
TI  - Non-ionizing electromagnetic radiation: a study of carcinogenic and cancer
      treatment potential.
AB  - Non-ionizing electromagnetic radiation (NIEMR), particularly the magnetic field
      component, has been implicated in the development of human neoplasia. Research
      suggests that if these fields are part of the carcinogenic pathway, they may act
      as a promoter or in the progression of established cancer. Active progression of
      cancer cells by NIEMR negate the possible early detection of clinically silent
      neoplasms. We have observed the effect of non-ionizing electromagnetic fields on
      an established breast carcinoma cell line MCF-7, and found no stimulation of
      growth when exposed to a low-frequency magnetic field. The same magnetic field
      has been used as an adjuvant to anti-neoplastic chemotherapeutic agents. The
      results of this study have shown an improvement in the neoplastic cell kill by
      antineoplastic chemotherapy when coupled with a low frequency magnetic field. Non
      ionizing electromagnetic radiation may be involved in the carcinogenic process;
      however, the answer to this question awaits further studies. We are exploring new
      methods of cancer treatment using non-ionizing electromagnetic radiation.

PMID- 7724879
TI  - Setting exposure limits for radiofrequency radiation and microwaves in China.
AB  - This review presents Chinese ELVs for radiofrequency radiation and microwaves.
      The ELVs were based on thermal or on non-thermal effects.

PMID- 7724880
TI  - The effects of radiofrequency (< 30 MHz) radiation in humans.
AB  - 121 workers who were exposed to RFR (< 30 MHz) over one year were examined. They
      were divided into two groups: one group was exposed to high electric field
      intensity (> or = 100 V/m), another to low intensity (< 100 V/m) and both groups
      were compared to control subjects. No significant changes in the functioning of
      the autonomic nervous system and blood parameters (Hb, WBC and blood platelets)
      occurred in the exposed subjects of either group. Some changes in ECG (ST-T
      interval and abnormal heart rate) were observed in the group exposed to high
      intensity (> or = 100 V/m) radiation. 100 V/m is suggested as an exposure limit
      for RF (< 30 MHz) radiation.

PMID- 7724881
TI  - Exposure limits for ultra-short wave radiation in work environments.
AB  - Exposure limit values for ultra-short wave radiation of humans were derived on
      the basis of epidemiological survey and experimental exposure of rabbits.
      Eighteen male rabbits were divided into 4 groups randomly. Three groups were
      irradiated with ultra-short waves (100 MHz) at 35, 1.5-3.5, and 0.07 mW/cm2 power
      density in an E-polarized TEM Cell at 24 +/- 4 degrees C ambient temperature. The
      last group in a sham chamber served as controls. Irradiation was performed 3
      hours per day, 5 days per week for 24 weeks. Thermal effects occurred in the
      group irradiated at 35 mW/cm2. The thermal threshold limit value was set at 1.5
      mW/cm2. An epidemiological survey was carried out on 136 factory workers and TV
      operators exposed over one year to ultra-short wave radiation at 0.2 mW/cm2. They
      were compared with 108 controls. The only complaint of the exposed group was
      neurosis. The exposure limit value (ELV) to short wave radiation was set at 0.2
      mW/cm2 by using a 15- and 20-fold safety factor.

PMID- 7724882
TI  - Long term effects of a 50 Hz electric field on the life-expectancy of mice.
AB  - The objective of our study was to determine the effect of an electric field (EF)
      on the life-span of mice. Male and female mice were paired and separated into two
      experimental groups: EF exposed and controls. The exposed mice were subjected to
      a 50 Hz, 10 kV/m electric field for 20 h/day. Offspring from both groups were
      identified as generation one and allowed to live for 18 months. Offspring from
      generation one were identified as generation two and allowed to die naturally.
      The age at which death occurred in both groups was recorded and post mortem
      examinations were performed. The obtained results were statistically analyzed by
      means of the chi-squared test. A statistically significant higher incidence of
      deaths before 18 months occurred in the first generation of the exposed group.
      The second generation of the exposed group showed a higher incidence of death at
      an earlier age. No increased incidence of malignant tumors nor any single
      specific cause of death was disclosed in the exposed animals. The results of this
      study indicate that continuous long-term exposure to a 10 kV/m electric field may
      shorten life-expectancy.

PMID- 7724883
TI  - Study of the effects of 50 Hz magnetic field on embryonic development: dependence
      on field level and field vector.
AB  - We studied the influence of power frequency and vector of EMF on avian and
      mammalian embryogenesis at a high level of magnetic induction (10 mT professional
      exposures and using therapeutic devices of Czech provenance) and at a low level
      (6 microT-environmental occurrence). No significant alterations of either avian
      or mammalian embryogenesis were found after repeated exposures to 50 Hz MF at 10
      mT or 6 microT, nor with different vectors.

PMID- 7724884
TI  - Interaction of MF 50 Hz, 10 mT with high dose of X-rays: evaluation of
      embryotoxicity in chick embryos.
AB  - We studied the combined effects of exposure to magnetic field (MF) 50 Hz 10 mT
      and X-ray ionizing radiation on developing chick embryos. When chick embryos at
      early stages were repeatedly exposed to MF prior to X-ray radiation, reduction of
      X-ray teratogenicity was observed. When MF exposures started immediately after X
      ray radiation, the adverse developmental effects of ionizing radiation were
      potentiated. Embryotoxicity was more pronounced in X-ray irradiated and MF
      exposed groups. We present a hypothesis about the mechanisms of MF effect based
      on enhancement of oxidative processes, followed by stimulation of antioxidant
      systems.

PMID- 7724885
TI  - Use of lectins as indicators for magnetic field action on erythrocyte membranes.
AB  - The effects of magnetic fields on biological membranes in general and on the red
      blood cell membrane in particular have been studied intensively in the last two
      decades. A variety of methods for evaluation of magnetic field action on the
      structure and function of biological membranes has been used. It has been
      suggested /1/ that the cell membrane can be considered as one of the primary
      targets affected by magnetic field exposure.

PMID- 7724886
TI  - Charge transfer in cell compartments--the problem of its adequate description.

PMID- 7724887
TI  - [Molecular study of 6 episodes of nosocomial infections produced by methicillin
      resistant Staphylococcus aureus].
AB  - A critical step in any epidemiologic research concerning nosocomial infections is
      the precise identification of the responsible pathogen. The present work utilized
      a molecular approach -plasmids identification, restriction length polymorphism
      DNA analysis, and random amplified polymorphic DNA- for the characterization of 6
      nosocomial outbreaks due to 52 strains of methicillin-resistant Staphylococcus
      aureus (MRSA). In these episodes, the clinic-epidemiologic and phenotypic
      analysis (antibiotype) pointed to a nosocomial infection. Through molecular
      analysis it was possible to establish, in a very precise way, clonality due to
      MRSA strains in 2 of the studied outbreaks; the same type of analysis allowed to
      eliminate a MRSA clonal origin in the remainder 4 episodes. The antibiogram was
      not an useful analytic tool due to its poor discriminatory power. Also, through a
      PCR procedure, it was possible to identify the presence of the gen mecA in every
      of the 52 MRSA strains studied.

PMID- 7724888
TI  - [Influence of ethnic and environmental factors the lipid profile in school
      children from the VIII Region].
AB  - We studied fasting total, HDL cholesterol and triglycerides in 329 children aged
      from 6 to 15 years. One hundred and ten lived in Concepcion and were considered
      urban. Two hundred nineteen lived in Alto Bio-Bio and were considered rural; of
      these, 173 had a pehuenche aboriginal origin. Rural pehuenche, rural non
      pehuenche and urban children had a total cholesterol of 123.7 +/- 23, 133.7 +/-
      25.8 and 153.7 +/- 29.7 mg/dl respectively, a HDL cholesterol of 39.2 +/- 9.1,
      38.8 +/- 9.1 and 46.2 +/- 11.3 mg/dl respectively and triglycerides of 83.3 +/-
      33.5, 96.7 +/- 33.5 and 81.9 +/- 33.3 mg/dl respectively. Lipid levels were above
      safe values in 2.9% of pehuenche, 8.7% non pehuenche rural and 13.6% or urban
      children. It is concluded that the higher lipid levels of urban and non pehuenche
      children supports the favorable effect of rural environment and pehuenche ethnic
      origin on cardiovascular risk factors.

PMID- 7724889
TI  - [Modification of the lipid profile of human placenta by moderate maternal
      undernutrition].
AB  - The lipid composition of human placenta phospholipids, coming from 9
      undernourished women that gave birth to low weight newborns and 9 well nourished
      women, was analyzed using gas-liquid chromatography. Phospholipids of placentas
      coming from undernourished women, when compared to well nourished women, had
      significantly lower amounts of w-6 and w-3 fatty acids (40.1 +/- 1.5 vs 42.4 +/-
      1.4 and 6.0 +/- 0.7 vs 7.1 +/- 1.3% respectively). The calculated mean melting
      point was higher in plancetas coming from undernourished women. It these women,
      the low content of polyunsaturated fatty acids and its replacement by short chain
      fatty acids was not able to balance the high mean melting points. The relative
      deficiency of essential fatty acids, the low saturation index and the high mean
      melting point of undernourished women's placental phospholipids, may suggest a
      lower membrane fluidity and a subnormal essential fatty acid content of fetal
      organs, that are essential for normal growth and development.

PMID- 7724890
TI  - [Psychosocial and familial variables associated with teenage pregnancy].
AB  - Preventive measures for teenage pregnancy (TP), would decrease infant mortality,
      early undernutrition and statal social expenditure. The cost of programs for TP
      would decrease with a sensitive risk indicator. We searched some pysoshocial and
      familial parameters, useful to built up this indicator. Self esteem (Piers-Harris
      test), intrafamilial relationship (Familial Apgar of Magdaleno) and the use of
      break time were studied in 60 pregnant teenagers (PT), 60 non pregnant teenagers
      at a low risk of pregnancy (LRP) and 60 non pregnant teenagers at a high risk of
      pregnancy (HRP). PT and HRP showed lower self esteem than LRP (88.3, 70.0 Y 41.6%
      respectively, under 7 points) lower familial Apgar (61.6, 50 y 8.3% under score
      6) and lower the quality of use of break time (66.7, 74.1 y 31.7% respectively
      with regular or deficient quality). The self esteem, intrafamilial relationship
      hand use of break time were associated to early pregnancy and high risk of
      pregnancy. These parameters are important to built up a sensitive risk indicator
      of early pregnancy in order to decrease the prevalence of this serious problem.

PMID- 7724891
TI  - [Morphine infusion for postoperative pain management in patients who have
      undergone upper abdominal surgery].
AB  - We compared the efficacy and side effects of postoperative continuous infusions
      versus intermittent intravenous on-demand morphine, with or without the addition
      of clonixin. Eighty five healthy patients, aged 18 to 65 years, scheduled for
      elective cholecystectomy, were prospectively randomized: Group 1 (n = 22)
      received morphine 2.5 mg i.v. on-demand; group 2 (n = 22) received a clonixin 400
      mg/day i.v. infusion; group 3 (n = 19) a morphine 0.4 mg/kg/day i.v. infusion;
      and group 4 (n = 22) received a clonixin 400 mg/day plus a morphine 0.4 mg/kg/day
      i.v. infusion. Groups 2, 3 and 4 also received, on-demand, 2.5 mg i.v. bolus
      doses of morphine. A blind observer recorder analogue and descriptive pain
      scores, respiratory rates and side-effects for 72 hours postoperatively. Groups
      with morphine infusions had less overall pain scores for the first day when
      compared with intermittent dosing (p < 0.05); these groups also had less pain
      during the night (p = 0.0016) and required less additional morphine (p < 0.0001).
      Side-effects were similar and no cases of heavy sedation or respiratory
      depression were observed. We conclude that a morphine 0.4 mg/kg/day infusion is a
      safe and effective alternative to on demand dosing in healthy patients after
      elective cholecystectomy, achieving better analgesia without increasing side
      effects. Clonixin 400 mg/day seems to add no significant benefits.

PMID- 7724892
TI  - [Adult pulmonary stenosis: percutaneous balloon valvuloplasty].
AB  - The results of balloon valvuloplasty as treatment for pulmonary stenosis in 8
      adults (6 male) whose ages ranged from 17 to 58 years are presented. Three
      patients had been subjected to cardiac surgery 32, 40 and 10 years before. The
      procedure was performed through the right femoral vein using one or two balloons
      with a diameter of not less than 20 mm, without complications and excellent
      tolerance. The pulmonary gradient and the right ventricular pressure were reduced
      in 7 patients from 81.4 +/- 26.9 to 26.6 +/- 11.3 and from 99.3 +/- 25.5 to 47.7
      +/- 13.6 mm Hg respectively (p < 0.0005). During follow up, 6 of the patients
      have remained in functional capacity I and in two, Doppler ultrasound examination
      showed a further reduction in valvular gradient. These results are in accordance
      with other reports and confirm that this technique is the treatment of choice for
      adult pulmonary stenosis.

PMID- 7724893
TI  - [Prevalence of digestive symptoms in normal adult women and its association with
      cholelithiasis].
AB  - The aim of this work was to study the prevalence of biliary diseases and
      digestive symptoms in normal adult women. Four hundred nineteen women were
      chosen; of these 145 were discarded due to previous gastrointestinal diseases
      (20), previous gastrointestinal complaints (38) and previous cholecystectomy
      (85). Two hundred seventy six women were subjected to abdominal ultrasound
      examination; of these 53 had cholelithiasis and in three a gallbladder cancer was
      suspected (and confirmed by surgery). Considering women with previous
      cholecystectomy, cholelithiasis and gallbladder cancer, a 33.6% prevalence of
      biliary diseases can be inferred. An interrogation about gastrointestinal
      symptoms was performed to women subjected to ultrasound examinations, by 2
      professionals unaware of ultrasound results. A high frequency of pyrosis, food
      intolerance and constipation was found, not observing differences between women
      with or without cholelithiasis. However, these last women had a higher frequency
      of upper abdominal pain. Both groups had also a high rate of previous surgical
      procedures.

PMID- 7724894
TI  - [Perineal endometriosis. Clinical experience with 8 patients].
AB  - We report our experience with 8 women with perineal endometriosis managed in a
      period of 20 years. All were multiparae women presenting with cyclical perineal
      painful masses related to menstrual periods. Symptomatology started 6 months to
      16 years after last delivery. Three patients had partial involvement of the anal
      sphincter. The endometriosis area was locally resected in all women. There were
      no complications and no problems with anal continence. Two patients had local
      recurrences. The different lapses between delivery and symptomatic presentation
      can be related to the amount of endometrial basal cells implants in the
      episiotomy. The treatment is always surgical. All endometrial implants must be
      resected and sphincteric structures must be repaired posteriorly.

PMID- 7724895
TI  - [Hereditary chronic pancreatitis. Report of a case].
AB  - Childhood hereditary pancreatitis is a rare entity of uncertain etiology,
      characterized by recurrent episodes of acute pancreatitis, abdominal pain and
      other unspecific symptoms. Among several therapeutic alternatives,
      pancreatojejunostomy is presently the treatment of choice. We report a 17 years
      old male with chronic hereditary pancreatitis that was treated with
      pancreatojejunostomy drainage.

PMID- 7724896
TI  - [POEMS syndrome. A case report].
AB  - A 48 years old male is reported. He presented with lower limb progressive and
      severe polyneuropathy, hypertrichosis, endocrinological alterations
      (hypothyroidism and hypogonadism) and organomegaly (hepatosplenomegaly and
      lymphadenopathies). This syndrome was associated with an osteosclerotic myeloma.
      The patient died two months after admission.

PMID- 7724897
TI  - [Cardiac involvement in polymyositis--dermatomyositis associated with Sjogren's
      syndrome].
AB  - A 41 years old woman with polymyositis-dermatomyositis with cardiac involvement
      is presented. The patient evolved with congestive heart failure, the
      electrocardiogram showed a left anterior hemiblock, lack of progression of R
      waves from V1 to V4 and unspecific ST and T alterations. Echocardiogram and
      cardiac catheterization showed global ventricular disfunction and pulmonary
      hypertension. An endomyocardial biopsy performed at the apex of the right
      ventricle showed mononuclear inflammatory infiltration, myocardial fiber
      degeneration and fibrosis. Initially, the patient responded well to diuretic,
      vasodilator and steroid therapy. Posteriorly she developed an atrial flutter that
      required electrical cardioversion and later died suddenly during the course of an
      acute pneumonia.

PMID- 7724899
TI  - [Ethical and clinical decisions in a terminally ill cancer patient with
      metastatic cancer. The problem of euthanasia].
AB  - The easiness of medical technology to prolong life in patients with severe
      cognitive or biological deterioration, the existence of cultural tendencies that
      underscore the importance of patient's self determination and economical
      considerations have posed the problem of euthanasia among patients, their
      families, society and medical teams. A propos of an exemplary patient, the
      ethical principles that allow the distinction between passive euthanasia and
      withdrawal of life support measures are analyzed. The analysis of active
      euthanasia, leads to the conclusion that it is not compatible with the ethical
      principles that classically have inspired medical actions.

PMID- 7724898
TI  - [Cardiovascular diseases secondary to active and passive smoking].
AB  - This articles reviews the effects of smoking on the cardiovascular system.
      Smoking accelerates and aggravates atherosclerosis and increases the risk of
      coronary artery disease and its clinical manifestations (unstable angina, acute
      myocardial infarction and sudden death), cerebrovascular diseases, aortic
      aneurysms and peripheral artery occlusive diseases. Smoking is considered the
      most important modifiable risk factor for these diseases. Fortunately, quitting
      smoking reduces and even normalizes cardiovascular risk.

PMID- 7724900
TI  - [The training of specialists. The case of nephrologists].
AB  - Specialists must be trained in properly certified university centers. There are
      established applicant selection programs and mechanisms and faculties maintain a
      favorable learning environment. The careful selection of teachers must be based
      in their personal attributes, their interest and dedication to academic work and
      their real concern about ethical issues. The center's technological equipment, as
      a means to favor the action of future specialists, is considered important.
      Several critical aspects of the training centers that, at the present time
      threaten post graduate training, are mentioned. The teaching activities of
      scientific societies and private and public health organisms should concentrate
      around training centers to reinforce their academic work, favoring their
      scientific and practicing activities. The interests of faculties and Ministry of
      Health medical centers should be made compatible for their own benefit. Medical
      specialties are closely interrelated. Therefore, the boundaries of nephrology
      should be established to define a training program. A common environment for
      pediatric and adult nephrology should be created, training centers should be
      accredited and specialists should be certified using common criteria. Our country
      has a deficit of nephrologists and scientific societies should encourage
      cooperative actions between the different training centers.

PMID- 7724901
TI  - [Laparoscopic cholecystectomy and gallbladder carcinoma].

PMID- 7724902
TI  - [Traffic accidents as a cause of death in Chile].

PMID- 7724903
TI  - [Resuscitative thoracotomy].

PMID- 7724905
TI  - [A study on the usefulness of stress assessment based on the THP health
      measurement--comparison with the general health questionnaire].
AB  - Although the "Total Health Promotion Plan (THP)" drawn up by the Labor Ministry
      includes a self-administered stress checklist (THP-SC) as a health measurement,
      THP-SC has not been utilized in the way that it had been planned. Hence, we
      studied the usefulness of this list by comparing it with the General Health
      Questionnaire (GHQ). We made a questionnaire that included both THP-SC and the 60
      item GHQ, and collected answers from 261 white-collar workers (male, average age
      43.7). The GHQ was evaluated using the Goldberg's method. When analyzing THP-SC,
      the number of answers indicating stress was counted, and the respondents were
      divided into two groups based on the cut-off points of 75 percentile or 90
      percentile. In the 60-item GHQ, 48 respondents out of 243 with valid answers had
      a higher score than the cut-off point, and in the 12-item GHQ, 77 out of 256 had
      a higher score. The average number of THP-SC was 5.67 +/- 3.19. Concerning the
      relationship with GHQ, many items of the 'A' section of THP-SC were significant.
      The comparison also suggested that four or more items checked in 'A' section or
      seven or more items checked in the whole list would mean that a respondent may be
      under stress.

PMID- 7724904
TI  - [Self esteem, affectivity perception, aims, and risk behaviors among teenagers of
      both sexes].
AB  - A self applied and anonymous enquiry was answered by 948 teenagers (600 female),
      participating in an integral health education plan and coming from a school
      located in a low income community of Metropolitan Santiago. Twenty nine percent
      came from single or foster parent families and 18.4% of parents were separated.
      Nineteen percent of women and 9.8% of men felt that they were not loved by their
      parents; 30.5% of women and classified as bad or regular their relationship with
      their fathers and 22.1% of men similarly classified their relationship with their
      mothers. Eighteen percent of men and 16.5% of women ignored their parent's
      educational level. Ten to 24% had a negative self image and 50% were unsure about
      their study goals. Forty eight percent of men and 25.5% of women had get drunk;
      24.1 and 12.8% had smoked marihuana. Half of the sample manifested attraction to
      dangerous situations; 22% had participated in quarrels and 34% had attacked other
      people. Twenty three percent of men and 35% of women had considered committing
      suicide. It is concluded that the lack of affection, a deteriorated self image,
      difficult parental relationships and orientation toward violence appear as the
      main problems in this sample of teenagers.

PMID- 7724906
TI  - [Obesity and liver dysfunction in UOEH employees--multiple regression analysis of
      the annual physical checkup data of 1991].
AB  - For the purpose of evaluating the significance of obesity as a risk factor toward
      various chronic geriatric diseases, a multiple regression analysis was performed
      on the annual physical checkup data of UOEH employees in 1991. The following
      results were obtained. (1) The average obesity index of the UOEH employees showed
      a progressive and significant increase in the 10 years from 1981 to 1991. (2) A
      close relation between the obesity index and serum GPT was recognized by
      elevation of the standard partial regression coefficients of serum GPT to obesity
      index and that of the obesity index to serum GPT when the data from all 1591 UOEH
      employees were analysed in one group. This finding was derived from a significant
      contribution of obesity to the liver dysfunction in the young male obese
      population under 30 years of age. (3) Systolic blood pressure was related to age
      rather than the obesity index, indicating that the development of hypertension is
      more closely related to aging than obesity. (4) No significant relation was found
      between the serum total cholesterol level and the obesity index in any group
      analysed. From the above findings, it can be suggested that the obesity in young
      male employees is more closely related to liver dysfunction than other
      abnormalities.

PMID- 7724907
TI  - [A case of pulmonary hyalinizing granuloma with its occupational history of dust
      exposure].
AB  - Multiple pulmonary nodules were found in a patient who had an occupational
      history of coal mining for eleven years and road construction for fifteen years.
      An open lung biopsy was performed, because nodules had increased in size compared
      to previous ones and a trasbronchial biopsy was not diagnostic. The nodules were
      composed of dense concentric lamellar collagenous structures with a serpentine
      pattern surrounded by an infiltration of histiocytes, lymphocytes and plasma
      cells with Russel bodies. These findings are compatible with pulmonary
      hyalinizing granuloma (PHG) named by Liebow A. A. The etiopathogenetic mechanism
      and the difference between PHG and silicotic nodule is discussed.

PMID- 7724909
TI  - Adaptive assignment versus balanced randomization in clinical trials: a decision
      analysis.
AB  - We compare balanced randomization with four adaptive treatment allocation
      procedures in a clinical trial involving two treatments. The objective is to
      treat as many patients in and out of the trial as effectively as possible.
      Randomization is a satisfactory solution to the decision problem when the disease
      in question is at least moderately common. Adaptive procedures are more difficult
      to use, but might play a role in clinical research when a substantial proportion
      of all patients with the disease are included in the trial.

PMID- 7724908
TI  - [A case of diffuse brain injury involving the medial part of the brain--its
      difference from diffuse axonal injury].
AB  - A 30-year-old male clinico-pathological case survived for 1 year and 9 months
      after being hit by a truck while riding on his motorbike on Aug. 21, 1988. On
      admission, his consciousness level was 5 according to the Glasgow Coma Scale, and
      a traumatic intraventricular hemorrhage and cerebral contusion were revealed by
      CT scanning. He underwent immediately an operation in order to drain blood from
      the ventricles at which time a right side dominant quadriplegia was noted. He
      made a gradual improvement and by January 1989 was able to tell us his name and
      address correctly. However, he remained incontinent and bedridden owing to the
      contracture of joints. He was put on rehabilitation exercises in March 1989 which
      trained him to operate a wheelchair. In April 1990 he regained urinary control,
      but was remarkably devoid of will power, perseverance and memory. He expired of
      pneumonia on May 11, 1990. At autopsy, his brain weighed 1180g. The cerebral
      convexity was discolored, especially the rectal gyri and bilateral olfactory
      bulbs were brownish-yellow. Old gross contusional scars were observed on the left
      rectal and orbital gyri, and the 3rd ventricle and inferior horns of the lateral
      ventricles were enlarged. Holzer's method revealed fibrillary gliosis in the
      corpus callosum, fornix, cingulate gyrus and a part of the caudate nucleus
      adjacent to the thalamus. Microscopically, axons were seen to be disrupted in the
      corpus callosum as well as in the anterior commissure, having the appearance of
      macrophages. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7724910
TI  - Binary regression with continuous outcomes.
AB  - Clinical research often involves continuous outcome measures, such as blood
      cholesterol, that are amenable to statistical techniques of analysis based on the
      mean, such as the t-test or multiple linear regression. Clinical interest,
      however, frequently focuses on the proportion of subjects who fall below or above
      a clinically relevant cut-off value, as a measure of the risk of disease. The
      customary approach to analyse such data is to dichotomize the continuous outcome
      measure and use statistical techniques based on binary data and the binomial
      distribution. In this paper, we use a parametric approach and the framework of
      generalized linear models to fit various regression models, including the
      logistic, on the basis of the original continuous outcome. We consider the
      Gaussian and the three-parameter log-normal distributions for the continuous
      outcome, assessing both precision and bias under various conditions. In
      simulation analyses, we find that we are unable to fit some of the samples with
      the 'dichotomous' approach, but we can with the 'continuous' approach, and that
      the latter yields estimates between 25 and 85 per cent more efficient than the
      former. We illustrate the method, programmed using GLIM macros, with data from
      clinical studies of the risk of hypoxaemia during open thoracic surgery and the
      risk of nocturnal hypoglycaemia among diabetic children.

PMID- 7724911
TI  - Age-related standards for ordinal data: modelling the changes in visual acuity
      from 2 to 9 years of age.
AB  - The visual acuities of 1140 children between the ages of 2 and 9 years were
      measured using the Sonksen-Silver Acuity System (SSAS) from a distance of 3
      metres. Ordered logistic regression was used to construct smoothly changing age
      related reference ranges for the proportions of children at different ages
      expected to have acuities in each of three ordinal categories. Exponential
      functions of age fitted the data better than polynomials. The resulting reference
      ranges can be used to derive the ages at which a given percentage of children
      achieve each of the acuity cut-offs. However, since it is unlikely that all
      children will be available for testing at the exact appropriate age, two possible
      alternatives are introduced and discussed. First, a new ordinal category that
      would result in a chosen outcome at a pre-selected age is calculated. Secondly,
      because it may be more feasible to use the current SSAS system whilst varying the
      distance of measurement, age-related standards showing the distances required to
      give constant pass-rates with the usual letter-sizes are also presented.

PMID- 7724912
TI  - Comparison of additive and multiplicative models for reproductive risk factors
      and post-menopausal breast cancer.
AB  - The mathematical multistage model of carcinogenesis proposed by Breslow and Day
      indicates that if hormonal risk factors for breast cancer are late-stage
      carcinogens then the use of an additive model (excess absolute risk) should be
      preferrable to the present standard use of the multiplicative model (excess
      relative risk). To test different models, information from a large prospective
      study of 431,604 women aged 45-74 years in 1970 with follow-up to 1985 on
      reproductive factors and post-menopausal breast cancer mortality was used to
      compute goodness-of-fit statistics. The relative risk function, ranging from
      multiplicative to additive, was explored by changing the exponent in a power
      transformation. The analysis found evidence of better fit by the additive
      compared with the multiplicative models, consistent with the proposed
      mathematical model.

PMID- 7724913
TI  - Non-parametric estimation for the difference or ratio of median failure times for
      paired observations.
AB  - We propose a non-parametric method to calculate a confidence interval for the
      difference or ratio of two median failure times for paired observations with
      censoring. The new method is simple to calculate, does not involve non-parametric
      density estimates, and is valid asymptotically even when the two underlying
      distribution functions differ in shape. The method also allows missing
      observations. We report numerical studies to examine the performance of the new
      method for practical sample sizes.

PMID- 7724914
TI  - A simulation study of estimators for rates of change in longitudinal studies with
      attrition.
AB  - Many longitudinal studies and clinical trials are designed to compare rates of
      change over time in one or more outcome variables in several groups. Most such
      studies have incomplete data because some patients drop out before completing the
      study. The missing data may induce bias and inefficiency in naive estimates of
      important parameters. This paper uses Monte Carlo methods to compare the bias and
      efficiency of several two-stage estimators of the effect of treatment on the mean
      rate of change when the missing data arise from one of four processes. We also
      study the validity of confidence intervals and the power of hypothesis tests
      based on these estimates and their standard errors. In general, the weighted
      least squares estimator does relatively well, as does an analysis of covariance
      type estimator proposed by Wu et al. The best estimates of variance components
      are based on complete cases or maximum likelihood.

PMID- 7724915
TI  - Modelling covariate effects in observer agreement studies: the case of nominal
      scale agreement.
AB  - Correction for chance-expected agreement has become an accepted technique in the
      analysis of observer agreement data and may be particularly useful when the level
      of agreement achieved in different populations is compared. However, formal
      methods for making comparisons of chance-corrected agreement or, more generally,
      for studying the effects of covariates on chance-corrected agreement have not
      received much attention. For nominal scale agreement data we show how Tanner and
      Young's model for observer agreement can be applied to this problem. The models
      discussed can be fitted using existing software and certain model parameters have
      interpretations in terms of positive and negative agreement odds ratios. The
      proposed methodology facilitates investigation of issues such as confounding of
      covariate effects and interaction between covariates in their effect on chance
      corrected agreement. The methods outlined therefore allow observer agreement data
      to be analyzed in a manner strongly analogous to the logistic modelling of the
      association between disease and suspected risk factors. The methods are
      illustrated using data on the comparability of primary and proxy respondent
      reports of the primary respondents participation in physically vigorous leisure
      time activity.

PMID- 7724916
TI  - A comparison of methods that characterize pulses in a time series.
AB  - There is general recognition that some glands secrete hormones primarily as a
      series of pulses. One can generally classify the proposed methods of pulse
      identification and characterization as either (i) criterion-based, that is, they
      use a criterion such as a test statistic to identify a rise and/or fall in
      hormone level within a moving window, or (ii) model-based, that is, they specify
      a statistical model for the time-varying portion of the signal and estimate its
      parameters. Using simulated data, we compare and contrast seven criterion-based
      methods and three model-based methods. The model-based methods perform better in
      estimating the parameters of interest; they are most effective with the sampling
      rate chosen so that there are 3-5 samples taken during the half-life of the
      hormone. At higher sampling rates the methods may overidentify pulses (false
      positives) and at lower sampling rates they may miss pulses (false negatives),
      both of which lead to biased estimates for the parameters of the signal.

PMID- 7724917
TI  - Divergent biases in ecologic and individual level studies.

PMID- 7724918
TI  - The dilemma of caring science.

PMID- 7724919
TI  - A comparison of nursing implications for elder care in Sweden and the United
      States.
AB  - The number of elderly are increasing at a rapid rate in both Sweden and the
      United States. Despite differences in governance, size, and health care systems,
      the two countries share similar problems and, perhaps, similar responses to care
      of aging persons. International educational exchange of successful interventions
      can promote better delivery of nursing care in both countries.

PMID- 7724920
TI  - Science and tradition in the nursing discipline--a theoretical analysis.
AB  - The purpose of the article is to argue for a conception of nursing knowledge that
      stresses theoretical and practical knowledge as equally important, and to analyze
      the roles of nursing science and nursing tradition in the discipline of nursing.
      Nursing knowledge is characterized as involving values, sets of beliefs, and
      procedural knowledge. Practical nursing knowledge is viewed as an integration of
      values, beliefs and procedural knowledge into action, whereas theoretical
      knowledge is viewed as a conception of nursing. Nursing tradition is described as
      the main organizer of practical nursing knowledge at the collective level, and
      nursing science as the main organizer of collective theoretical knowledge.

PMID- 7724921
TI  - Nursing absenteeism--one determining factor for the staffing plan.
AB  - The purpose of the present study was to quantify factors which contribute to the
      absenteeism of nursing personnel and affect staffing patterns. Absenteeism in a
      general hospital was studied for the period 1975-1990 in relation to the number
      and level of nursing personnel, the number of discharged patients in the same
      period, and the existing relevant policy. The variables were analyzed by the
      multiple regression method having an initial estimator the existing situation in
      1990 and what is expected for the year 2000. The results showed that the mean
      value days of absenteeism for each registered and assistant nurse in 1975 was
      22.4 days and in 1990, 51.9 days, sickness raised from 12.6 days in 1975 to 16.6
      in 1990, maternity from 9.1 in 1975 to 25.3 in 1990, educational leave for
      registered nurses was 0.02 in 1975 and 3.8 in 1990 and for assistants 2.1 in 1985
      and 17.3 in 1990 due to the new policy, and social fringe benefits raised from
      0.71 days in 1975 to 3.65 in 1990. The expected rate of absenteeism by the year
      2000 will be 67 to 83 days per person, an increase by 56% in relation to 1990
      data.

PMID- 7724922
TI  - Parental participation in the care of hospitalized children.
AB  - The purpose of this study was to investigate those parts of the care of
      hospitalized children that their parents perform, the nursing tasks the parents
      themselves felt they could manage and whether parents' and staff members'
      opinions coincided. A questionnaire was given to parents of children between one
      week and five years of age who were hospitalized at a pediatric surgical
      department during a 6-week period (n = 40), a similar questionnaire being
      distributed to all the staff (n = 44). The results indicate that parents stay
      with their children during hospitalization and that they take responsibility for
      their children's basic care and needs. Parents and staff members believed that
      parents might be able to take on a greater share of caring activities if they
      were given instruction and support, though there was disagreement as to which
      nursing tasks are appropriate for parents to take on.

PMID- 7724923
TI  - Stroke patients in long-term care--the relatives' conception of functional
      capacity and appropriate care.
AB  - The closest relatives of 29 permanently institutionalized stroke patients were
      interviewed about their relationship to the patient before and after stroke, the
      functional ability of the patient before and after stroke, and their opinion of
      an appropriate care setting for the patient. The patients had all been
      independent before stroke, but were now dependent on help with most primary
      activities of daily living. Twelve patients had severe communicative
      difficulties. Most relatives could not suggest a realistic alternative to nursing
      home care, due to the patients' severe disabilities and extensive need for care.
      One patient was, however, later discharged to a sheltered living facility in
      accordance with her relative's wishes. One-third of the relatives expressed need
      for more information and support and wanted to take part in a support group. The
      nursing staff need high competency in providing good care for the patients and
      offering psychological support to the relatives, and should include the relatives
      in the overall treatment plan.

PMID- 7724924
TI  - Characteristics of low back pain patients who do not complete physiotherapeutic
      treatment.
AB  - Patients' problems in following recommendations of health professionals is an
      issue of great concern. The purpose of the present study was to investigate
      whether patients with low back pain (n = 46) who dropped out of a treatment
      programme differed in characteristics measured prior to treatment from a matched
      comparison group (n = 46) who completed the programme. Data collected on work
      disability and sick leave, frequency, duration and intensity of pain, physical
      function, and personality characteristics were compared. The results indicated
      that the groups differed significantly on 3 of 16 variables. The non-completers
      had been on sick leave for a longer time period prior to treatment, experienced
      more intense pain and performed at a lower level on the test of physical function
      than those who completed the treatment programme.

PMID- 7724925
TI  - Health-care screening among the elderly--a comparison between participants and
      non-participants.
AB  - Geriatric screening at health clinics has become a regular feature of the health
      care services offered in some Norwegian municipalities. Normally there is good
      participation in such screening programmes, but there are always some non
      attenders. There is little published material showing the intervention needs
      among non-respondents. In a municipality in the middle parts of Norway, screening
      was offered to the municipality's elderly inhabitants at the local health clinic.
      Those who did not attend were offered a domiciliary visit. The findings indicate
      that there is a category of people among those who do not attend for screening at
      the health clinic who have less need of a medical examination and socioeconomic
      support than those who do attend the screening. There is also a category in need
      of community nursing, technical aids and health care because of senile dementia,
      depression and unsought social isolation.

PMID- 7724926
TI  - Ability to solve problems, professionalism, management, empathy, and working
      capacity in occupational therapy--the professional self description form.
AB  - The majority of occupational therapists in Sweden previously worked on large
      occupational therapy wards. Health care policy has changed over the years and the
      system has been reorganized accordingly. The employment situation for
      occupational therapists has also changed. This paper focuses on the perception of
      professional self among occupational therapists. The objective was to explore the
      professional self and to suggest components important to the occupational
      therapist profession. The Professional Self Description Form (PSDF) was used for
      the exploration of self. The 19 items in the PSDF cover areas relevant to
      professional functioning and activity. Sixty-eight employed occupational
      therapists participated. The results of the PSDF were subjected to factor
      analysis and five factors were obtained; Ability to solve problems,
      Professionalism, Management, Empathy, and Working capacity. We believe that these
      five factors can function as improving domains of the role of the professional
      occupational therapist in Sweden.

PMID- 7724927
TI  - Evaluation of a Swedish version of the Ostomy Adjustment Scale.
AB  - The main aim of the present study was to adapt an instrument measuring patients'
      adjustment to life with an ostomy to Swedish conditions and to test reliability
      and validity of the adapted instrument. The Ostomy Adjustment Scale (OAS), which
      is focused on three domains: physical function, psychologic state, and social
      interaction, was selected as suitable. After translation into Swedish,
      equivalence and internal consistency of the scale were calculated. Subjects with
      various types of urine or faeces diversions were recruited for self-rating with
      the OAS and a visual analogue scale estimating total quality of life (QOL). The
      instruments were tested in 48 patients with five different diagnoses, 36 with and
      12 without ostomy, and re-tests were carried out in 25 of the patients.
      Reliability (Cronbach's alpha) was 0.95. A positive correlation was found between
      the OAS and QOL (r = 0.67), indicating that the instrument has some validity.

PMID- 7724928
TI  - Distribution of working time and contents of physiotherapy activities in a
      clinical setting--methodological considerations.
AB  - The purpose of the present study was to collect personnel utilization data in the
      physiotherapy department of a general hospital as a basis for improving the
      practice of physiotherapy. Over a four-week period in a process of continuous
      observation 12 physiotherapists recorded their activities under predefined task
      categories. The percentages of total time used in the observed activities were as
      follows: direct patient treatment 31%, other work (planning, recording, arranging
      walking aids and student guidance) 10%, and cooperation (consultation, meetings,
      arranging patients' affairs, counselling relatives and parents) 9%. The
      proportion of uncategorized work amounted to half of the total working time.
      Physical exercise and counselling in direct patient care, preparation and records
      in other work and teamwork and cooperation with parents were the commonest
      activities recorded. The physiotherapists' time schedule in the different wards
      differed in terms of mean treatment time per patient and amount of patients per
      day. The major problems were felt to be the lack of assessment methods of follow
      up and feed-back systems for patients after hospital care and uncertainty as to
      what the content of practise should contain. The observation method appeared to
      be a useful tool for collecting personnel utilization data in a physiotherapy
      department.

PMID- 7724929
TI  - Network in scientific publishing.

PMID- 7724930
TI  - The VIPS-model used by nursing students--review of educational care plans.
AB  - The VIPS-model developed by Ehnfors et al. (1991) for nursing documentation and
      writing of care plans was used and evaluated by nursing students in connection
      with their final assignments. In addition to their evaluation by the use of a
      questionnaire, the students' written care plans were reviewed. Three instruments
      were used, two were tested in earlier studies when reviewing registered nurses'
      care plans, and one was developed especially for this review of the quality of
      the students' care plan assignments. The results showed that the key words for
      nursing assessment were evaluated as both useful and easy to use while the key
      words for nursing interventions were considered useful but more difficult and
      were used to a less extent. Many students did not document any outcome or any
      discharge notes. The instruments that were used for the review of the care plans
      were of great help in analyzing the use of the model as well as the content and
      comprehension of the key words.

PMID- 7724931
TI  - Perceptions of caring behaviors and patient anxiety and depression in cancer
      patient-staff dyads.
AB  - Cancer patient and staff perceptions of the importance of caring behaviors
      (Caring Assessment Instrument, CARE-Q) and patient levels of anxiety and
      depression (Hospital Anxiety and Depression Scale, HADS) were determined in 19
      matched patient-staff dyads. Both groups perceived comforting and anticipating
      behaviors to be among the most important ones. Patients considered behaviors
      focused on staff explaining and facilitating to be more important than did staff,
      whereas staff rated behaviors concerning accessibility as more important than did
      patients. Patient and staff perceptions of the importance of comforting behaviors
      were negatively associated. No significant mean value difference or correlation
      was found on the HADS anxiety or depression subscales. Members of matched patient
      staff dyads did not agree strongly on the importance of caring behaviors and
      patient levels of anxiety and depression.

PMID- 7724932
TI  - Cancer patients' hopes and expectations of nursing practice in Stockholm-
      patients' descriptions and nursing discourse.
AB  - Although nursing literature on 'caring' has proliferated in recent years,
      relatively little empirical data exists about which aspects of nursing practice
      are those recognized and valued by patients. The purpose of the qualitative study
      presented here is to explore the manner in which one group of Swedish patients
      describe and explain the domain of nursing. The data presented derives from
      interviews with persons diagnosed with cancer during 1987 at one general hospital
      in the greater Stockholm area. Forty-six patients were interviewed in 1988-89,
      and 20 of these survivors were interviewed again in 1992. The domain of nursing
      practice 'expected' by the patients was seen to be defined positively, both by
      what nurses 'are' and 'do', as well as negatively, by what they do not do. It was
      found that the patient--nurse contact, as described by these patients, was
      between an individual patient and a nursing collective. Finally, the need for
      local rather than global criteria for evaluating nursing care is discussed.

PMID- 7724933
TI  - Testing a Swedish version of OCAIRS on two different patient groups.
AB  - Occupational Case Analysis Interview and Rating Scale (OCAIRS) is an instrument
      for assessing occupational performance. Consisting of a semi-structured interview
      and a rating scale, OCAIRS is based on the Model of Human Occupation (Kielhofner
      1985) and has been translated into Swedish. The rater reliability of the Swedish
      version (OCAIRS-S) was tested on two different populations: acute psychiatric in
      patients and patients suffering from chronic muscular pain. The Intraclass
      Correlation Coefficient and the Percentage Agreement methods were used to
      calculate the strength of agreement between raters. Content validity was tested
      using the Percentage Agreement method. Research results indicate that the
      instrument has a reasonable rater reliability. Although the content validity
      study produced insufficient information, it nevertheless supports the use of
      OCAIRS-S as a reliable instrument. Further research and development on the
      instrument is recommended.

PMID- 7724934
TI  - Life control among young men in view of their childhood and adolescence.
AB  - The analysis of life control and its development is an issue of central concern
      to modern health research. This article discusses longitudinal questionnaire data
      in an attempt to identify factors that predict young men's life control in early
      childhood and adolescence. No factors in the childhood family background
      predicted strong life control in adulthood. A positive development in the
      family's social situation showed a positive association with life control in
      adulthood. Poor school performance and unhealthy habits in adolescence were
      associated with poor life control in adulthood. According to a regression
      analysis, the following factors predicted a strong life control in adulthood:
      regular physical exercise, positive changes in the family's social situation, no
      school class repeats, no experimentation with intoxicants in adolescence,
      admission into intermediate level of education, and no smoking in adolescence. It
      is crucially important for purposes of health promotion to identify factors which
      predict life control in adulthood. By helping adolescents to achieve life
      control, we are also helping them to cope with developmental tasks and therefore
      to promote their health.

PMID- 7724935
TI  - The impact of public health in Norwegian postgraduate programmes of psychiatric
      nursing.
AB  - The purpose of this descriptive study was by means of a questionnaire to obtain
      data on how 13 nursing schools, offering a postgraduate specialization in
      psychiatric nursing in Norway, have incorporated a public health perspective into
      their curricula. Since the mid-1980s, national health policies and Health for All
      by A.D. 2000 have placed emphasis on decentralization of all health care
      services, including services for the mentally ill. The Community Health Law of
      1984 guarantees all Norwegian citizens such services in their local communities.
      The schools have traditionally emphasized curative services in hospitals, rather
      than health promotion and preventive measures at community level. Are the new
      graduates prepared for psychiatric work at community level? A content analysis of
      a semistructured questionnaire revealed that a social psychiatric perspective has
      indeed been incorporated in today's curricula. This was supported by reviewing
      the required reading lists for each of the 13 schools. Roughly one can say that
      the schools represent two perspectives: 1) those focusing primarily on relational
      aspects, and 2) those focusing on relational aspects within a social psychiatric
      framework.

PMID- 7724936
TI  - [Clinical case of the month. Apropos of a case of amiodarone-induced lung
      disease].

PMID- 7724937
TI  - [Origin, prevention and treatment of decubitus ulcers].

PMID- 7724938
TI  - [BOOP: bronchiolitis obliterans organizing pneumonia, myth or reality?].

PMID- 7724940
TI  - [Study of sinus variability using temporal and spectral analysis: value and
      perspectives].

PMID- 7724939
TI  - [Interventional breast disease management].

PMID- 7724941
TI  - [Major principles of general medical terminology].

PMID- 7724942
TI  - [How I examen... a patient with suspected hypoglycemia].

PMID- 7724943
TI  - [Drug of the month. Lansoprazole (DakaR)].

PMID- 7724944
TI  - [What is your diagnosis? Sinus rhythm with complete right bundle branch block and
      status following antero-septal infarct].

PMID- 7724945
TI  - [Beta blockers in secondary prevention following acute heart infarct].
AB  - Prospective studies have confirmed a preventive effect of beta-adrenergic agents
      in the early as well as the late postinfarction period. In the early
      postinfarction period (first week), mortality is decreased by 13% by a lower
      incidence of myocardial ruptures and by stabilization of the size of the
      infarcted area. Prevention of reinfarction and sudden cardiac death in the late
      period of secondary prevention (up to six years) leads to additional reduction of
      mortality by 22 to 35%, depending on the risk group. The preventive effect of
      beta-blocking agents is not only attributed to their anti-ischemic properties but
      also to their antihypertensive, antiarrhythmic and antithrombotic effects. Beta-1
      selective and not selective blockers show preventive effects. Beta-1-selective
      blockers are preferred because of fewer side effects. The effect of partially
      agonistic beta-blocking agents is low and thus of no use for secondary
      prevention. The elimination pathway and the price should be considered in the
      choice of the beta-blocking drug.

PMID- 7724946
TI  - [Beta blockers in arrhythmias].
AB  - Beta blockers are effective antiarrhythmic agents. In this survey we discuss the
      indications of beta blockers in supraventricular tachycardias as well as in
      ventricular tachyarrhythmias. Clinical studies of beta blockers in myocardial
      infarction are reviewed. In patients with suspected infarction and without
      contraindications, early treatment with an intravenous dose is of paramount
      importance. Oral therapy should be continued for at least a year or two. Although
      only few data are available on the effects of beta blockers in preventing sudden
      death in patients who have not suffered a myocardial infarction, it may be
      reasonable to treat all patients with cardiac arrest due to ventricular
      fibrillation--irrespective of etiology--unless there is a strong
      contraindication. Nevertheless, the favorable results of treatment with
      cardioversion defibrillators must be considered.

PMID- 7724947
TI  - [Beta blockers in heart insufficiency].
AB  - Congestive heart failure is common. Since prognosis depends on activation of
      neurohumoral systems, treatment with beta-blocking agents seems to be appropriate
      in spite of their negative inotropic effects. According to the results of the
      studies published hitherto, mortality was not reduced by beta blockers, but the
      clinical course, symptoms and hemodynamic parameters were influenced positively,
      particularly in patients with congestive cardiomyopathy. Further studies are
      necessary in order to establish specific advantages of beta-blocking agents in
      patients with heart failure, before they are recommended for routine therapy in
      medical practice.

PMID- 7724948
TI  - [Beta blockers and bronchial asthma].
AB  - Worsening or precipitation of asthma by beta-adrenoceptor antagonists is well
      recognized. Severe bronchoconstriction may be induced even in 'mild' asthmatics,
      and the dose of beta blocker required may be low, as in the case of eye drops of
      timolol, a nonselective beta blocker used to treat glaucoma. The severity of
      bronchoconstrictor response is not predictable. Nonselective beta blockers are
      more likely to precipitate bronchospasms in patients with asthma. The mechanism
      of beta-blocker-induced asthma is still not certain. Normal subjects develop
      neither a deterioration in lung function nor an increased bronchial
      hyperreactivity; therefore, beta blocker drugs should in general be avoided by
      asthma patients. Safe alternative therapies exist for both hypertension (calcium
      antagonists, ACE inhibitors, diuretics) and ischemic heart disease (calcium
      antagonists, nitrates).

PMID- 7724950
TI  - [Complement in 1994: clinical importance and perspectives].

PMID- 7724949
TI  - [What is your diagnosis? Heart aneurysm, sinus bradycardia and 1st-degree AV
      block].

PMID- 7724951
TI  - [Cardiac interventions in Switzerland 1993].
AB  - As in the previous years, a survey of all cardiac invasive, interventional and
      surgical procedures was carried out 1993 by a detailed questionnaire, which was
      sent to all Swiss centers. The resulting data are presented here for the whole of
      Switzerland and per individual center. The outstanding findings are: For the
      first time, more coronary angioplasties than coronary bypass graft operations
      were performed. At the same time, angioplasty in two or more vessels during the
      same session was attempted in 10% only. Overall the coronary stent represents the
      most frequently used new device in interventional cardiology in Switzerland, but
      large differences regarding the incidence of stent implantations exist among the
      centers. Compared with the public or university hospitals, the private centers
      have increased their interventional and surgical volume dramatically during the
      past years.

PMID- 7724952
TI  - [Multiple familial glomangiomas].
AB  - Multiple glomus tumours represent a special variant of glomangiomatosis. Based on
      our observation, the clinical features, diagnosis and differential diagnosis are
      presented and possible therapeutic approaches are discussed.

PMID- 7724954
TI  - [Knee joint arthroscopy in the growth years].
AB  - An increasing number of children and adolescents are complaining about knee pain.
      Because of unspecific patient history and the difficulty of clinical examination
      a correct diagnosis can be made in only half of the patients. The importance of
      the diagnostic and therapeutic knee arthroscopy has therefore increased.
      Indication, technique, complications and results are discussed.

PMID- 7724955
TI  - [A case from practice (321). Rubella arthritis].

PMID- 7724953
TI  - [Indications for, diagnostic conclusions and therapeutic consequences of
      echocardiography. Studies in a medium-sized hospital].
AB  - Within a period of three months indications and diagnostic as well as therapeutic
      consequences of all echocardiographic studies were investigated in a middle-size
      hospital. 174 of a total of 188 examinations were usable. Most examinations were
      performed in order to detect or to verify left-ventricular failure or coronary
      heart disease. The diagnostic and therapeutic consequences were enormous; more
      than 90% of all pathological findings were listed as diagnoses in the final
      medical report. In terms of valvular heart disease, pericardial effusion and left
      ventricular failure the echocardiographic study was most essential for diagnosis.
      In contrast most normal findings were seen with suspicion of coronary heart
      disease. Changes in medication or new prescription of oral anticoagulation, ACE
      inhibitors and beta-adrenergic antagonists were significantly related to the
      therapeutic recommendations of the echocardiographic studies. The recommendations
      concerning antibiotic prophylaxis of endocarditis or further diagnostic
      investigation were respected with few exceptions. Obviously little conclusion
      could be drawn from a normal echocardiographic study; a well-established
      indication is essential for the benefit of echocardiography.

PMID- 7724956
TI  - [What is your diagnosis? Sinus rhythm with antesystole in Wolff-Parkinson-White
      syndrome].

PMID- 7724957
TI  - [Necessity should become wish again].

PMID- 7724958
TI  - [Crystal-associated destructive arthropathy of the shoulder].
AB  - Crystal-associated destructive arthropathy of the shoulder is most commonly
      observed in elderly women. Functional impairment and social impact define its
      importance especially in this group. Clinical features include pain at rest and
      on use, large cool effusion and instability. Radiographs show attrition of bone
      and cartilage with a paucity of reparative changes. Synovial fluids are viscous,
      with low cell counts, and stain positively for the presence of apatite-containing
      particles and often also for calcium-pyrophosphate crystals.

PMID- 7724959
TI  - [Gastric lipoma as an unusual cause of upper gastrointestinal bleeding].
AB  - This is a case report of a gastric lipoma causing a severe upper gastrointestinal
      bleeding. About 200 cases of this very rare benign gastric tumor have been
      reported so far. Symptoms are not characteristic, but may also mimic malignancy
      when occurring with bleeding, obstruction or weight loss. Malignant
      transformation is possible, but extremely rare. Because the tumor is situated
      under the submucosal layer in 90%, preoperative diagnosis by endoscopic biopsy is
      almost never possible. The tumor has to be treated by resection. A diagnosis by
      frozen section during the operation is recommended.

PMID- 7724960
TI  - [Differential diagnostic aspects of progressive spastic paraplegia in adults with
      emphasis on neurometabolic diseases].
AB  - The differential diagnosis of a progressive spastic paraparesis in the young
      adult is broad and includes rare neuro-metabolic diseases like cerebro-tendinous
      xanthomatosis, adrenomyeloneuropathy and hypovitaminosis. Their clinical
      presentation as well as the result of paraclinical examinations can be similar to
      those of multiple sclerosis. The early recognition of these diseases is
      important, because a dietary regimen may reduce the severity and progression of
      symptoms and signs and genetic counselling can be important. The relevant
      biochemical examinations for their detection are discussed. These neuro-metabolic
      diseases have to be differentiated from other neuro-degenerative diseases like
      amyotrophic lateral sclerosis and hereditary spastic paraplegias.

PMID- 7724961
TI  - [A case from practice (322). Suspicion of hand, foot and mouth disease with acute
      virus disease cause by Coxsackie virus].

PMID- 7724962
TI  - [Atherosclerosis and menopause].

PMID- 7724963
TI  - [The threat syndrome of the anterior descending coronary artery].
AB  - Some patients with unstable angina develop a deep T-wave inversion in ECG leads
      V1 to V4. It has been suggested that this special ECG pattern is associated with
      a severe stenosis of the left anterior descending (LAD) coronary artery. We have
      studied 73 of this patients. All of them had an LAD involvement, nearly always as
      severe atherosclerotic plaque and in 5% of the cases due to non-atherosclerotic
      alterations (milking or spasm). Angioplasty was performed in 33% and bypass
      surgery in 61%. In both cases the immediate results were good (0% and 4%
      respectively in-hospital mortality) as well as the outcome (12% restenosis and 0%
      late mortality respectively). The ECG signs disappeared in the year after.

PMID- 7724964
TI  - [Controversies and progress in the management of idiopathic hypertrophic
      cardiomyopathy].

PMID- 7724965
TI  - [Dynamic cardiomyoplasty with latissimus dorsi muscle. An alternative to heart
      transplantation?].

PMID- 7724966
TI  - [New pharmacologic agents: amlodipine++].

PMID- 7724967
TI  - [Applications of nuclear magnetic resonance in the diagnosis of cardiopathies].
AB  - Applications of nuclear magnetic resonance imaging in cardiovascular diagnosis.
      The role of magnetic resonance imaging in the evaluation of cardiovascular system
      is still evolving. Nevertheless, this technique is of great promise for cardiac
      patient management in the near future. Magnetic resonance imaging provides a high
      contrast between the blood pool and myocardial function that has been shown to be
      effective for the evaluation of a wide variety of anatomic abnormalities as well
      as to assess cardiac contractile function or myocardial perfusion. Moreover,
      magnetic resonance spectroscopy has provided a new research tool for the
      evaluation of myocardial metabolism. Such performances indicate the potential of
      magnetic resonance techniques to establish the link between myocardial function
      and metabolism. In this presentation we will review the current status of
      magnetic resonance imaging for the diagnosis and evaluation of a wide variety of
      cardiovascular diseases and discuss its future potential.

PMID- 7724968
TI  - [Mind and soma in our era].

PMID- 7724969
TI  - [Current epidemiology of tuberculosis].
AB  - A major health threat in developing countries, the incidence of tuberculosis has
      decreased steadily in Western countries over the last century. However, since
      1986, first in the United States, then more recently in several European
      countries, the number of declared cases has increased. The current epidemiology
      of tuberculosis is presented with special emphasis on French data. The possible
      causes of this revival have been carefully analyzed: better registration, role of
      immunodepression and particularly the HIV epidemic, geographical origin, drug
      abuse, poor living conditions.... Based on the description of resistant forms and
      the observations of hospital epidemics, particularly in the United States and in
      patients with HIV infection, curative and preventive measures may and must be
      undertaken whenever a case of tuberculosis is observed.

PMID- 7724970
TI  - [Prevalence of pneumocystosis in HIV infected patients in a pneumology unit.
      Autopsy study performed in Abidjan (Cote d'Ivoire)].
AB  - Autopsies were performed in the Pathology Department of the Treichville
      University Hospital, Abidjan, Ivory Coast in 70 HIV infected subjects who had
      died in the Department of Pneumophtisiology. The prevalence of Pneumocystis
      carinii pneumonia was determined. None of the patients had received prophylaxis
      against P. carinii and none had bee treated for pneumocystosis. Autopsies were
      performed within 6 to 48 hours after death and the diagnosis of pneumocystosis
      was confirmed with the Gomori-Grocott staining technique on lung specimens. Among
      the 70 autopsies Pneumocystis carinii pneumonia was observed in 6. Thus the
      prevalence of P. carinii pneumonia in these patients infected with HIV was 8.57%.

PMID- 7724971
TI  - [Endoscopic case: she was "between the sheets!"].

PMID- 7724972
TI  - [Plurifocal alveolar pneumonia in a patient with AIDS: disseminated Mycobacterium
      avium intracellulare infection with difficult diagnosis].
AB  - In patients with the acquired immunodeficiency syndrome (AIDS), manifestations of
      generalized Mycobacterium avium intracellulare infection are non-specific and
      pneumopathy is rarely encountered. We report a case of a patient with AIDS who
      had clinical and radiological manifestations of multifocal alveolar pneumopathy
      which was found on autopsy to be due to disseminated Mycobacterium avium
      intracellulare.

PMID- 7724973
TI  - [Radiation-induced cancer after treatment of mediastinal seminoma. Apropos of a
      case].
AB  - Radiation-induced cancer is a rare complication of radiotherapy. The diagnosis
      relies on chronological, topographical and histological data distinguishing the
      lesion from tumoural relapse. We report the case of a second cancer, meeting the
      criteria of radiation-induced malignancy, and attempt to define the frequency,
      clinical situations and risk man. In addition to gentic mechanisms, other factors
      appear to play a role in the genesis of radiation-induced cancer.

PMID- 7724975
TI  - [Radiological case: diagnosis of left para-cardiac opacity].

PMID- 7724974
TI  - [Thoracic meningocele and neurinoma complicating von Recklinghausen disease.
      Value of imaging in therapeutic management. Apropos of 2 cases].
AB  - We report two cases neurogen tumors (neurinoma and meningocele) in
      neurofibromatosis. The progress of imaging techniques, with the use of CT and
      MRI, is helpful for evaluating these patients, distinguish malignant from benign
      neoplasm and screening the therapeutic indication.

PMID- 7724976
TI  - [Pierre-Marie-Bamberger syndrome and hydro-aeric lesion].

PMID- 7724978
TI  - [Is PCR a pertinent diagnostic device of tuberculosis in 1994? Groupe ECRIR.
      Entretiens du Club de Reflexion sur l'Infection Respiratoire].

PMID- 7724977
TI  - [A new case of spontaneous regression of metastasis of kidney cancer].

PMID- 7724979
TI  - [Antiphospholipid syndrome and the pneumologist].
AB  - The antiphospholipid syndrome (APS) is usually defined by the association of a
      clinical manifestation (venous or arterial thrombosis or miscarriage) with the
      presence of antiphospholipid antibodies (lupus anticoagulant and/or
      anticardiolipin antibodies). It frequently occurs in the course of systemic lupus
      erythematosus but is also encountered as a "primary" disease. APS is responsible
      for diverse respiratory manifestations. Pulmonary embolism is common. The site of
      the causal venous thrombosis is frequently unusual. Pulmonary hypertension may be
      a consequence of repeated embolism or may belong to the primary idiopathic
      variety. Pulmonary manifestations may also result from left-sided heart failure
      due to mitral or aortic valve abnormalities, myocardial infarction or a specific
      myocardiopathy. APS is probably involved in the occurrence of some cases of adult
      respiratory distress syndrome. Long term secondary prevention of recurrent
      thrombosis is a central point in the management of APS.

PMID- 7724980
TI  - [For a better recognition of occupational respiratory diseases].

PMID- 7724981
TI  - [Neo-adjuvant chemotherapy of locally advanced non-small cell bronchial cancers].
AB  - Locally advanced non-small cell lung cancers have a poor prognosis following
      surgery alone when this has been possible, because of a high rate of local and
      metastatic relapses. Probability of five years survival for these patients ranges
      between 5 and 15%. Thus, locally advanced non small cell lung cancer for which
      resection is potentially possible but poorly curative are usually designated as
      marginally resectable. Adjuvant postoperative chemotherapy or radiation therapy
      hardly seem to improve survival. Therefore, other combined modality treatments
      might be proposed. Neoadjuvant chemotherapy may be used for non small cell lung
      cancer in an attempt (a) to improve complete resection rate and (b) to treat non
      detectable metastatic disease. Numerous phase II studies have demonstrated the
      faisability of this combined modality in locally advanced non small cell lung
      cancers, particularly in stage N2 patients. Until the results of the ongoing
      phase III studies would be known, neoadjuvant chemotherapy might be considered as
      an investigational approach.

PMID- 7724982
TI  - [Surgery of bronchial cancer in patients aged 75 and over].
AB  - From April 1984 to December 1990, 66 patients 75 years of age or older underwent
      curative mediastinal lymph node dissection. There were 37 pneumonectomies. Post
      operative mortality was 12% and was not affected by the type of dissection. Five
      year survival was 16.2 +/- 6.29% (median 23 months) and was more than 45% in less
      elderly patients. Survival rate was highly affected by presence of metastasis in
      the mediastinal nodes and was zero in N2 cases. More than half of the patients
      died from cancer-related causes. Generally, we operate all the N2 cases which
      appear technically dissectable. Retrospectively, we think that N2 stage detected,
      and confirmed histologically in patients over 75, would be the only contra
      indication for this attitude.

PMID- 7724983
TI  - [Pleural fibrous mesothelioma. Apropos of a case].
AB  - A 27-year-old man with an uneventful history was hospitalized after fortuitous
      discovery of an opacity in the right lung field. The clinical examination
      revealed a multi-nodular euthyroidian goiter. Laboratory tests, including blood
      glucose, were normal. Computed tomography of the chest showed a pleural formation
      and associated pleural effusion. Complete surgical exeresis led to the diagnosis
      of benign fibrous pleural mesothelioma. Fibromas of the pleura are rare and
      usually discovered due to extra thoracic signs. The clinical course is long and
      often silent. Surgical removal is indicated and usually is complete.

PMID- 7724984
TI  - [Interstitial pneumopathy in a woman treated with althiazide].
AB  - The authors report the case of interstitial pneumopathy in a woman treated with
      althiazide, thiadizical diuretic. This observation bring the discussion on
      responsibility to this drug in the origin of this pulmonary disease.

PMID- 7724985
TI  - [Refractory hypoxemia caused by transient opening of the foramen ovale after
      pneumonectomy].
AB  - A patient with bronchogenic cancer underwent right pneumonectomy. Surgical and
      infectious criteria were normal during the postoperative period when immediate
      postoperative severe hypoxeamia occurred. Pure oxygen only incompletely corrected
      the situation. Transoesophageal echocardiography with injection of microbulles
      for contrast imaging demonstrated a right-left shunt due to an open foramen
      ovale. Reopening the foramen ovale is rare but well documented complication of
      pneumonectomy. The pathogenics is still debated since hyperpressure in the right
      atria usually is not present. Echocardiography with contrast test is the best
      means of making the diagnosis.

PMID- 7724986
TI  - [Small-cell carcinoma of the trachea in a 27-year-old patient].
AB  - A rare small-cell carcinoma of the trachea was observed in a 27 year-old man.
      Treatment included chemotherapy and radiotherapy as for bronchogenic small cell
      carcinomas. This treatment regimen led to complete but temporary remission. The
      patient died 4 months after the end of the treatment due to multiple cerebral
      metastases.

PMID- 7724987
TI  - [Association of pseudochylothorax and pleural tuberculosis. Apropos of a case].
AB  - The authors report a case of pseudochylothorax revealed by pleural tuberculosis.
      Classically, pseudochylothorax is a late complication of chronical and calcified
      pleurisy especially sequellae of tuberculosis treated by induced pneumothorax.
      Treatment consist on thoracentesis or aspiration with frequent remove. Surgical
      decortication can be useful. Specific chemotherapy is only necessary in the
      patients in whom tuberculosis is present or never treated with antibiotics.

PMID- 7724988
TI  - [Bilateral and multiple round pulmonary opacities].

PMID- 7724989
TI  - [Right hilar mass and pleural effusion].
AB  - One case of bronchogenic cyst associated with a pleural effusion is reported.
      Computed tomography and magnetic resonance imaging (MRI) findings are described.

PMID- 7724990
TI  - [Pulmonary cryptococcosis: an uncommon opportunistic infection in AIDS on the
      Ivory Coast].

PMID- 7724991
TI  - [Bilateral pneumothorax of unusual origin].

PMID- 7724992
TI  - [Release of balloons].

PMID- 7724993
TI  - [Limitations of transtracheal anesthesia in bronchial endoscopy].

PMID- 7724994
TI  - Effects of exercise on synovium and cartilage from normal and inflamed knees.
AB  - The effect of running activity on normal and inflamed knees was determined by
      light microscopic (LM) and scanning electron microscopic (SEM) observations on
      hamster articular cartilage. Animals were split into two groups; one housed in
      standard cages and one given free access to running wheels. Twenty-one days prior
      to analysis, half of each group was given an intra-articular injection of
      lipopolysaccharide (LPS) to cause an inflammation, the other half were
      uninjected. No remarkable changes were observed by LM in either the control
      running or nonrunning groups. In contrast, cartilage proteoglycan depletion, and
      pannus and synovial hyperplasia were equally observed in both groups of LPS
      injected animals. SEM observations on the patellae from control animals found
      them to be free from damage to the articular cartilage. The joints of both the
      LPS nonrunning and running animals contained synovial hypertrophy with villus
      projection from the synovial lining. However, only the LPS-injected running
      hamsters had cartilage fraying over large areas of the articular surface, as well
      as areas in which the villus projections had been flattened. These results
      demonstrated that mechanical stress applied to a proteoglycan-depleted cartilage
      enhances the breakdown of the collagen matrix as judged by fibrillation, and may
      aggravate the inflammation by crushing the swollen synovial lining where it
      encroaches on the joint space.

PMID- 7724995
TI  - Influence of interleukin-1 beta, tumour necrosis factor alpha and prostaglandin
      E2 on chondrogenesis and cartilage matrix breakdown in vitro.
AB  - Inflammatory mediators such as the cytokines interleukin-1 (IL-1) or (TNF alpha),
      and prostaglandins [predominantly prostaglandin E2 (PGE2)] are generally
      considered to be involved in the breakdown of cartilage matrix in
      chondrodestructive diseases, especially rheumatoid arthritis and osteoarthritis.
      Their mode of action is not yet completely understood. Blastemal cells or
      differentiated chondroblasts/chondrocytes of limb buds from mouse embryos (day
      12) in organoid cultures provide an efficient system to investigate the mechanism
      of action of these substances. Using recombinant human IL-1 beta, TNF alpha and
      PGE2 alone or together (in pairs) in this culture system, we found that none of
      these substances alone could affect chondrogenesis. TNF alpha, however, when
      combined with IL-1 beta, proved to be the more potent cytokine causing a
      transformation of embryonal chondrogenic cells into fibroblast-like cells and
      thus inhibiting the expression of the cartilage cell phenotype. This might be due
      to inhibition of both the morphogenetic and cytodifferentiation phases of
      chondrogenesis. The well-known synergistic interaction between both cytokines
      seems to be phase limited and may not occur in the postchondrogenesis phase. In
      addition, our results showed that TNF alpha alone or combined with PGE2 caused a
      marked breakdown of the cartilage matrix. These in vitro findings might be useful
      to elucidate the complexity of interactions between different cytokines and PGE2
      involved in cartilage destruction processes in vivo.

PMID- 7724996
TI  - Serum IL-4, IL-10 and IL-6 levels in inflammatory arthritis.
AB  - As the available in vitro and in vivo data suggest that interleukin (IL)-4 and IL
      10 have immunosuppressive activity, our hypothesis was that serum IL-4 and IL-10
      levels would correlate inversely with parameters of inflammation in patients with
      inflammatory arthritis. IL-4 was detected in the serum of 12 out of 140 patients
      with rheumatoid arthritis (RA), which was increased compared to the proportion
      found with patients with osteoarthritis (OA; P < 0.02). In addition, IL-4 was
      detected in the serum of 2 of 19 patients with systemic lupus erythematosus
      (SLE), 2 of 24 patients with psoriatic arthritis and 1 of 5 patients with
      Behcet's syndrome. No IL-4 was detected in patients with the following
      conditions: OA (58 patients), gout (17 patients), ankylosing spondylitis (6
      patients), Reiter's syndrome (6 patients), polymyalgia rheumatica (6 patients),
      temporal arteritis (5 patients) and scleroderma (3 patients). No IL-10 was
      detected in any of the sera tested. We discuss the possible relevance of these
      results to the regulation of the immune response evident in inflammatory
      arthritis.

PMID- 7724997
TI  - Fibrinolysis and coagulation abnormalities in systemic lupus erythematosus.
      Relationship with Raynaud's phenomenon, disease activity, inflammatory indices,
      anticardiolipin antibodies and corticosteroid therapy.
AB  - Endothelial cell damage in systemic lupus erythematosus (SLE) was evaluated by
      measuring fibrinolytic activity and von Willebrand factor levels. Tissue-type
      plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI)
      activity, and von Willebrand factor antigen (vWF:Ag) and activity (vWF:RCof) were
      measured in 21 SLE patients (12 of whom were therapy free) and 22 controls. In
      addition, the relationship between such parameters and Raynaud's phenomenon,
      disease activity [according to personal criteria, Systemic Lupus Activity Measure
      (SLAM) and European Consensus Lupus Activity Measurement (ECLAM) scores]
      inflammatory indices [ESR, C-reactive protein (CRP), alpha 2-globulin],
      anticardiolipin antibodies and corticosteroid therapy was investigated. Lower
      levels of t-PA antigen (P = 0.003) and higher levels of vWF:Ag (P = 0.001) were
      found in SLE patients in comparison with controls. Moreover, t-PA antigen was
      lower (P = 0.02) in steroid-free patients in comparison with those taking
      steroids. No relationship was found between fibrinolysis and coagulation
      abnormalities and Raynaud's phenomenon, disease activity, inflammatory indices
      and anticardiolipin antibodies. Endothelial cell damage is probably a common
      feature in SLE patients; nevertheless, we were unable to clarify the nature of
      such abnormality. It is worth noting that low doses of steroids seem to be
      effective in improving endothelial cell function in SLE patients.

PMID- 7724998
TI  - Activated CD4+ and CD8+ T-cell subsets in Wegener's granulomatosis.
AB  - Several lines of evidence argue in favour of an involvement of T cells in the
      pathogenesis of Wegener's granulomatosis (WG). These include the presence of
      highly specific IgG autoantibodies to proteinase 3, perivascular T-cell
      infiltrates and elevated amounts of soluble interleukin-2 (IL-2) receptors in
      patient's serum. In order to further address this question we evaluated by double
      immunofluorescence and flow cytometry the expression of several cell surface
      molecules associated with T-cell activation. As compared to healthy controls (n =
      15), the CD4+ subset was significantly diminished, while the percentage of CD8+ T
      cells was elevated in WG patients (n = 24). Within the CD4+ T-cell subset we
      found a highly significant increase in activation/memory markers (CD25, CD29, HLA
      DR). Within the CD8+ T-cell subset the expression of CD11b, CD29 and CD57 was
      significantly elevated, while the expression of VD28 was reduced. The use of 10 V
      beta-, 1 V alpha- and 1 V gamma-specific monoclonal reagents failed to reveal any
      significant bias in the peripheral T-cell receptor V-gene repertoire of WG
      patients. There was also no correlation between T-cell activation markers and
      laboratory parameters [C-reactive protein (CRP), ESR], disease duration or
      therapy. A significant correlation was found only for the degree of organ
      involvement and the increase in CD4+ T cells coexpressing HLA-DR, as well as the
      increase in CD57 expression on CD8+ T cells. In conclusion, both CD4+ and CD8+ T
      cell subsets were activated in WG. Cytotoxic CD8+CD57+CD11b+CD28- T cells may
      directly contribute to damage of vascular endothelium.

PMID- 7724999
TI  - Basic Research and Clinical Application in Human Tumor Immunology and Molecular
      Biology. 22nd meeting of the Society for Oncodevelopmental Biology and Medicine.
      Groningen, The Netherlands, September 18-22, 1994.

PMID- 7725000
TI  - [Macrocytic anemia in adults. Physiopathology, etiology, diagnosis, treatment].

PMID- 7725001
TI  - [Psychomotor development in infants and young children].

PMID- 7725003
TI  - [Decubitus ulcer. Etiology, physiopathology, prevention].

PMID- 7725002
TI  - [Acute diarrhea. Diagnostic orientation and emergency treatment].

PMID- 7725004
TI  - [Cauda equina syndrome. Diagnosis].

PMID- 7725005
TI  - [Description and mechanisms of sclerotic arterial diseases of the lower limbs].
AB  - Sclerotic involvement of abdominal aorta and lower limb arteries is related to 2
      types of fundamental lesions: atherosclerosis and arteriosclerosis.
      Atherosclerosis is a focal intimal thickening (plaque) of large- and medium-sized
      arteries, which combines atheroma (lipid deposition) and fibrosis. Plaque rupture
      is the crucial event in the progression of atherosclerosis, directly causing most
      acute thrombotic events, and contributing in great part to plaque expansion.
      Arteriosclerosis is a diffuse fibrosis of the arterial wall with thickening of
      the intima, and thinning of the media. Two forms of arteriosclerosis probably
      exist with distinct mechanisms and consequences. Obliterating arteriosclerosis
      mainly involves leg arteries (causing poor distal run-off) and appears to be
      essentially enhanced by ageing, diabetes and chronic renal insufficiency.
      Dilating arteriosclerosis involves large arteries where it provokes aneurysm
      formation; it is related to ageing, but seems also to be dependent upon an inborn
      dystrophy of arterial connective tissue. These 3 components of sclerotic arterial
      diseases of the lower limbs are often combined in the same individual.

PMID- 7725006
TI  - [Epidemiology and natural history of arterial diseases of the lower limbs].
AB  - Symptomatic arterial disease in the legs is common and asymptomatic disease is
      even more common. However the majority of these patients do not develop disabling
      intermittent claudication and the local disease tends to run a benign course,
      particularly in women, with less than 10% to 15% ever requiring active
      intervention. With current therapy the incidence of major amputation is only 1%
      to 3%. By contrast however the very few patients who develop critical leg
      ischaemia have a prognosis as serious of that as an incurable malignant cancer.
      Only little over half of these patients will be alive without a major amputation
      a year after developing critical leg ischaemia. Perhaps the most important
      results of epidemiological studies in patients with arterial disease in the legs
      is that both symptomatic and asymptomatic disease increases mortality by a factor
      of 2 to 3 compared to subjects without significant arterial disease in the legs.
      One obvious implication of this is the need to redirect attention to the
      secondary prevention of cardiovascular morbidity or mortality in these patients
      even though their symptoms may be confined to the leg.

PMID- 7725007
TI  - [Diagnosis of sclerotic arterial diseases of the lower limbs].
AB  - Diagnosis and treatment of lower limbs arterial disease do not depend exclusively
      on functional staging. Fontaine's classification has to be replaced by a
      classification based on clinical and complementary investigations to understand
      better the evolutive risks, and guide management. Distal systolic pressures along
      with symptom analysis and clinical examination allow a more precise diagnosis.
      Complementary investigations aim at assessing, the localization and extension of
      atherosclerotic lesions; the severity of tissue ischaemia. The concept of
      critical ischaemia has tried to insure greater diagnostic homogeneity for
      patients with rest ischaemia. The role of complementary investigation can only
      increase for the diagnosis and management sclerotic arterial disease. The
      detection of the other localizations of atherosclerosis and arteriosclerosis are
      essential to prevent complications which are responsible for the prognosis of the
      disease. Sclerotic arterial diseases represent approximately 90 to 95% of the
      causes of arterial diseases. Identification of these other causes remains,
      however, essential as it can greatly influence prognosis.

PMID- 7725008
TI  - [Evaluation of the coronary risk in sclerotic arterial diseases of the lower
      limbs].
AB  - The prevalence of coronary artery disease is very high among patients with
      peripheral arterial disease. The fate of these patients mainly depends on their
      coronary risk. Most often, the evaluation of coronary risk is performed when a
      surgical intervention on the aorta or lower limb arteries is decided. However,
      the late risk, at medium and long term, of coronary disease is much higher than
      its immediate perioperative risk. Diagnostic work-up is complex. Symptoms of
      coronary insufficiency may be masked by the limited capacity to physical
      exercise, but remain essential indices. None of the available complementary
      investigations has a satisfactory predictive value. Diagnostic explorations and
      therapeutic decisions for coronary heart disease have to be discussed in each
      case, according mainly to age and symptoms, and to whether peripheral arterial
      surgery is required.

PMID- 7725009
TI  - [Arterial disease of the lower limbs in diabetic patients].
AB  - Lower limb arterial disease in diabetics resembles that in non diabetics.
      However, some important differences include the vessels involved and the extent
      of the involvement. In the diabetic, the arteries most frequently involved are
      those below the knee. Arterial occlusions are bilateral, multisegmental, and
      involve unusual vessels such as the internal iliac artery, the deep femoral
      artery, the small branches and the collateral circulation. Arterial disease in
      the diabetic appears at a younger age, advances more rapidly, is more diffuse,
      and is almost as common in women as in men. Interaction of arterial disease,
      neuropathy and infection produces a wide away of clinical findings, including
      callus formation, foot ulcers, cellulitis, osteomyelitis and patchy areas of
      gangrene. Foot abscess and cellulitis require emergency debridement and drainage.
      Arterial reconstruction, including endovascular procedures, lessen the rate of
      amputation, allow partial foot amputation, and prevent from recurrent foot ulcer.
      Soft tissue repair, and especially fasciocutaneous flaps or musculocutaneous
      flaps, provide the means to heal most of the patients without infection, and
      avoid below-knee amputation.

PMID- 7725010
TI  - [Cholesterol embolism in the lower limbs].
AB  - An atheromatous aorta may be the source of micro-emboli composed of cholesterol
      crystals. These cholesterol emboli presumably result from dislodgment of
      atheromatous material occurring either spontaneously, or consecutively to a
      coronary angiography, an aortic surgery or even an anticoagulant or thrombolytic
      treatment. Even if the best known clinical feature is the "blue toe" syndrome
      together with renal insufficiency, the spectrum of disease caused by cholesterol
      emboli ranges from asymptomatic to rapidly progressive multiple system failure.
      Therefore cholesterol embolism is a serious complication of aortic
      atherosclerosis and often holds a poor prognosis. Diagnosis is confirmed by skin
      or muscle biopsy and fundoscopic examination. The optimal treatment remains to be
      established.

PMID- 7725011
TI  - [Medical treatment of sclerotic arteriopathies of the lower limbs].
AB  - The medical treatment of sclerotic arterial disease in the lower limbs is only
      one facet in the management of generalized arterial disease. Clinical and
      ancillary investigations estimate not only the severity of arterial
      insufficiency, but also the diffusion of arterial disease and the existence of
      threatening lesions. Medical treatment has 2 essential aims: to limit the
      progression of lesions by risk factor control and antithrombotic drugs; to
      improve arterial insufficiency using adapted rehabilitation and, if necessary,
      drugs with vasodilatating or haemorrheological properties.

PMID- 7725012
TI  - [Endovascular treatment of sclerotic arteriopathies of the lower limbs].
AB  - Percutaneous transluminal angioplasty is performed to treat arterial stenoses or
      occlusions. Currently, balloon angioplasty is still considered as the gold
      standard even if new interventional devices and techniques have been proposed to
      improve immediate and long-term results: stents, intraarterial thrombolysis,
      percutaneous aspiration embolectomy, atherectomy, laser and ultrasound
      angioplasty. Evaluations of these methods in the treatment of peripheral arterial
      diseases are ongoing. An interventional procedure is indicated only after a
      thorough analysis of the medical and anatomo-angiographic data. A stenosis or a
      short occlusion of the iliac or the femoro-popliteal arteries are typical
      indications for percutaneous angioplasty in case of claudication; more complex
      lesions become gradually accessible to percutaneous methods in patients with
      chronic critical and even acute arterial ischaemia of the lower limbs. During the
      follow-up, the development of a restenosis is detected by careful clinical
      examination and ultrasound duplex scanning.

PMID- 7725013
TI  - [Surgical treatment of sclerotic arterial diseases of the lower limbs].
AB  - Among arterial reconstruction procedures, thromboendarterectomy has progressively
      left place to prosthetic grafts for aorto-iliac surgery. At infra-inguinal level,
      inversed or in situ venous grafts allow distal revascularisations down to the
      foot. Lumbar sympathectomy keeps some indications. Indications depend upon the
      level of arterial obstruction, the symptoms, and the operative risk of the
      patient. At aorto-iliac level surgery provides excellent results; indications for
      proximal surgery are large; operative risk is the main limiting factor. At infra
      inguinal level surgery is well tolerated but permeability rates are not as good
      as with aorto-iliac surgery; distal surgery is appropriate only is case of
      critical ischaemia, when everything must be done for limb salvage.

PMID- 7725014
TI  - [Rheumatoid purpura. Diagnosis, development, prognosis].

PMID- 7725015
TI  - [Bacterial infections in newborn infants. Diagnostic criteria, treatment,
      prevention].

PMID- 7725016
TI  - [Hepatitis viruses].
AB  - Five different hepatitis viruses that cause acute and chronic hepatitis in human
      beings have been identified. Hepatitis viruses are designated by the letters A,
      B, C, D and E and abbreviated as HAV, HBV, HCV, HDV, and HEV, respectively.
      Although each belongs to a distinctly different virologic group, they share the
      feature of hepatotropism, which remains poorly understood. HAV and HEV are
      transmitted through a fecal-oral route. HDV, also referred to as the delta agent,
      is a defective, parenterally transmitted virus that uses the hepatitis B surface
      antigen (HBsAg) of HBV as its envelope. Thus, HDV infection occurs only in
      patient with HBV infection. Application of molecular biologic techniques has been
      instrumental in elucidating the genomic sequences of the individual hepatitis
      viruses and in understanding viral gene expression and mechanisms of viral
      replication. Knowledge of the genomic structure of these viruses and perfection
      of molecular biological techniques have also led to clinical applicability of
      molecular diagnostic techniques. Indeed, these molecular diagnostic techniques
      have rapidly become the standards against which serologic tests are compared.

PMID- 7725017
TI  - [Serum biological markers and screening of viral hepatitis].
AB  - The diagnosis of hepatitis A is based on IgM anti-HAV positivity. IgG anti-HAV
      indicates immunity from further infections of hepatitis A. In acute hepatitis B,
      HBs Ag is the first marker to appear in the serum, followed by HBe Ag and anti
      HBc. After recovery, HBs Ag disappears, anti-HBs appears with anti-HBe and anti
      HBc and persists for many years. Anti-HBs is indicative of recovery and immunity.
      Chronic hepatitis B infection is defined as the persistence of HBs Ag for more
      than 6 months. The presence of HBeAg and HBV DNA in the serum of HBsAg positive
      carriers has been considered as indication of active viral replication. After a
      variable period, often several years, viral replication disappears. The patient
      displays serum anti-HBe antibodies and HBV DNA is not detected in the serum. This
      state is the most frequently observed and has been classified as wild type.
      Mutations have been described. The delta virus is not able to replicate on its
      own, but is capable of infection when activated by the presence of hepatitis B
      virus. The appearance of serum IgG anti-delta is the simplest method of
      diagnosing delta infection. Serological tests for HCV detect antibodies to viral
      antigens (Elisa assay). Each positive anti-HCV assay must be followed by a
      complementary confirmation test. The most widely used method for supplementary
      testing is the recombinant immunoblot assay in which antibodies are sought for
      recombinant antigens of HCV coated on nitrocellulose strips.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7725018
TI  - [Transmission and prevention of viral hepatitis].
AB  - The ways of transmission of hepatotropic viruses are now fairly known.
      Populations at risk for these infections are precisely identified and preventive
      measures are efficient. Safe hygiene for oro-fecal as well as for sexual or blood
      transmission is accurately determined. Vaccines exist against some viruses. In
      the future, efforts will have to be made in several directions: a) education of
      individuals at risk, in order to further diminish the transmission of the viruses
      in these groups; b) identification of the mode of transmission of sporadic
      hepatitis which, so far, has escaped any prevention; c) design of a vaccine
      against virus C, which will make mass prevention possible.

PMID- 7725019
TI  - [Hepatitis C].
AB  - Hepatitis C is usually poorly symptomatic, particularly in the acute phase. After
      an incubation period ranging from 5 to 12 weeks, the symptoms are nonspecific and
      icterus is rarely present. Laboratory results are more suggestive, showing
      characteristic fluctuations in transaminases comprising periods with normal
      values. Chronic hepatitis is probable when elevation of transaminases persists
      for more than 6 months. Chronic virus C hepatitis is usually asymptomatic.
      Clinical manifestations are poorly specific and transaminase concentrations are
      generally little increased and variable in over 75% of the cases. Some
      histological lesions are more often observed in the chronic stage, particularly
      steatosis, presence of intraportal lymphoid nodules and bile duct involvement.
      The natural history is dominated by the risk of development to cirrhosis and
      hepatocellular carcinoma. A course to chronic hepatitis C is observed in 20 to
      70% of cases, while the risk of developing cirrhosis is between 10 and 38% within
      approximately 20 years. Prognosis is then linked to decompensation of cirrhosis
      and especially to the development of hepatocellular carcinoma, within
      approximately 10 years after appearance of cirrhosis, with a prevalence of at
      least 20%. The association of other factors such a hepatitis B virus or alcohol
      can accelerate this course.

PMID- 7725020
TI  - [Extra-hepatic manifestations of viral hepatitis].
AB  - A variety of prodromal symptoms of viral hepatitis (urticaria, fever,
      arthralgias, headache, polyradiculonevritis) are attributed to A, B, C, D or E
      hepatitis only when jaundice appears, and because they disappear with it.
      Spectacular extrahepatic symptoms (polyarteritis nodosa, cryoglobulinemia,
      glomerulonephritis, marrow aplasia...) may be associated with B or C hepatitis
      without any liver symptom. Some of the extrahepatic symptoms observed during
      chronic hepatitis C therapy with interferon (thyroid dysfunctions, cutaneo-mucous
      lichen) may be related to the immunomodulatory effects of interferon rather than
      to virus C itself.

PMID- 7725021
TI  - [Hepatitis B and C viruses and primary liver cancer].
AB  - Chronic infections by hepatitis B and C viruses are major risk factors for
      primary liver cancer. In both infections, induction of chronic active hepatitis
      followed by cirrhosis precedes development of the tumor and is a major mechanism
      of liver carcinogenesis. For hepatitis B virus, several elements indicate that
      the virus might also exert direct effects through cis and transactivation of
      cellular genes. For hepatitis C virus, such a direct effect has not yet been
      demonstrated.

PMID- 7725022
TI  - [Viral hepatitis and liver transplantation].
AB  - Chronic liver diseases due to hepatitis viruses are the main indication for liver
      transplantation. Recurrence of viral infection on the liver graft is responsible
      for the occurrence of chronic hepatitis, liver cirrhosis, or liver failure. The
      risk of viral recurrence may influence the indications for liver transplantation.
      The risk of viral B recurrence is higher in patients transplanted for viral B
      liver cirrhosis than for viral B-delta liver cirrhosis, and for fulminant
      hepatitis B. This risk is higher in patients with active viral B replication at
      time of transplantation. Long-term administration of anti-HBs immunoglobulins
      reduces significantly the HBV recurrence rate and the related mortality,
      especially in patients without active HBV replication at transplantation. Middle
      term results for patients transplanted for viral C related liver cirrhosis are
      good, but the recurrence rate of HCV infection is high. Protocols of prevention
      of HCV recurrence after transplantation are mandatory.

PMID- 7725023
TI  - [Trisomy 21. Epidemiology, diagnosis, prognosis].

PMID- 7725024
TI  - [Acute intestinal invagination in infants. Physiopathology, diagnosis,
      development, prognosis, treatment].

PMID- 7725025
TI  - [Threatened premature labor. Etiology, diagnosis, treatment].

PMID- 7725026
TI  - [Hypercalcemia. Etiology, diagnosis, treatment].

PMID- 7725027
TI  - [Oligoarthritis or polyarthritis of less than three months of development.
      Diagnostic orientation].

PMID- 7725028
TI  - [Lipothymia, syncope and brief loss of consciousness].

PMID- 7725029
TI  - [Confusion syndrome. Diagnostic orientation].

PMID- 7725030
TI  - [Epidemiology and psycho-social consequences of urinary incontinence].
AB  - Previous studies about urinary incontinence epidemiology are disparate.
      Incontinence affects about 7% of children between 5 and 14, without predominance
      of sex. Among adults, prevalence is higher for female. In male patients
      incontinence percentage varies between 1.4% and 2.9% according to the age, with a
      low increase in prevalence after the age of 40. In female population, the
      percentage varies between 4 and 57% according to age after 45, and menopause
      status. The menopause occurrence is not unanimous admitted as causal factor.
      Obstetrical traumatism, pelvic surgery, child enuresis, postpartum urinary
      incontinence increase the risk of urinary incontinence. Overall in France, we
      estimate that 39% of adult women have micturition disorder: 24% with urgency, 25%
      with pollakiurie and 21% with incontinence. A lot of studies underline that
      incontinence exists in young nullipara woman. Over the age of 65, prevalence of
      urinary incontinence is estimated between 14 and 55% (average 30%). Incontinence
      rate is higher in institution than at home.

PMID- 7725031
TI  - [Physiology of continence and micturition].
AB  - Continence and micturition result from an inversely related evolution of urethra
      and bladder pressures. On filling, the bladder pressure remains low and the
      urethral pressure is high: filling bladder pressure mainly depends on its visco
      elastic property while urethral pressure is actively kept high by the tonic
      activity of smooth and striated urethral sphincters, respectively maintained by
      sympathetic and somatic spinal reflexes. It is the other way round when the
      bladder empties: bladder pressure rises and urethral pressure lower, because the
      parasympathetic impulses brings about a massive contraction of the detrusor
      musculature, and a reflex relaxation of both sympathetic and somatic systems. In
      the adult, the reflex loop passes through the pontine center. The volitional
      control of this micturitional reflex, which is not only the privilege of human
      beings, implies an ability to recognize a specific feeling: the desire to
      urinate. It involves brain centers located in the inner aspect of the frontal
      lobe and in the underlying structures of the archaic cortex (limbic system).

PMID- 7725032
TI  - [Paraclinical explorations of urination disorders in men].
AB  - The uroflowmetry is still the only criteria to show and analyse a dysuria unknown
      by the patient two times out of three. This analysis will allow us to appreciate
      the follow-up of the desobstruction regarding the therapeutic which has been
      chosen. The ultrasonography (renal ultrasonography and prostate) can easily
      detect bladder and renal failures. It provides good information on anatomical and
      shape of the prostate but less information on urethral obstruction because
      dynamic ultrasonography is carried out in a few cases. The intravenous
      pyelography seems to be out of date but it will give the most important
      parameters to appreciate the urinary problems allowing the analysis of the
      physiological micturation by voiding urethrography. The retrograd urethrography
      provides good imaging diagnosis but gives a better image of urethral stenosis in
      a very important dysuria. It is not appropriate to say that it is an invasive
      procedure. The endoscopy is very convenient. It could be used during an
      examination and need no anesthetic to be performed with an optical fibroscope.
      The urodynamic examination is needed only in a major dysuria without real
      obstruction or detrusor instability. First the obstruction has to be evaluated by
      the previous examinations. It could point out that some bladders are
      hypocontractile and in these cases, surgery will be inappropriate. Also it allows
      us to test the effectiveness of external sphincter pressure to determine the
      prognostic of continence and even to treat the incontinence by biofeedback.

PMID- 7725033
TI  - [Surgery of urinary incontinence in men].
AB  - Male urinary incontinence needs usually a surgical treatment. Over-flow
      incontinence is due to bladder neck, prostatic or urethral obstruction and is
      treated by transurethral resection of the prostate or uretrotomy. Intrinsic
      sphincter deficiency needs an artificial sphincter implantation or an endoscopic
      periurethral injection of teflon particles or collagen. Incontinence due to
      detrusor over-activity is rarely treated by subtrigonal phenol injection or ileal
      detubularized cystoplasty augmentation.

PMID- 7725034
TI  - [Exploration of urinary incontinence in women].
AB  - The diagnosis of urinary incontinence is based on history and physical
      examination. For the patient, the incontinence is related with a wet vulva, but
      history differentiate stress from urge incontinence and note the associated
      urinary symptoms and alterations in bowel habit or sexual function. Physical
      examination confirms urinary incontinence and assess pelvic prolapses, perineal,
      muscle tone and skin condition. Specialized tests include imaging and urodynamic
      tests. Imaging tests are dynamics and identify the position and the aspect of the
      bladder neck during resting and straining view. Urodynamic tests are designed to
      determine the functional status of the bladder. They assess the detrusor
      function, the urethral pressure, the transmission of the pressure from the
      bladder to the urethra. After clinical evaluation and specialized tests, the
      urinary incontinence could be identified and evaluated so that an adapted
      treatment can be proposed.

PMID- 7725035
TI  - [Micturition disorders in women others than incontinence].
AB  - Micturitional disorders in the adult female occur more frequently than
      incontinence and are psychosocially more invalidating. Although they were long
      considered psychogenic, such disorders can now be more clearly divided into
      urgency-pollakiuria and micturitional difficulties. Although these symptoms can
      reflect severe disease of variable cause and duration, they can also be due to
      ineluctable physiologic changes in the female, subjected throughout life to the
      influence of hormones and to disfavourable anatomic conditions. These disorders
      are also sometimes the tribute of bladder "corticalisation" and of the highly
      reflexogenic character of the urethra. This article proposes a simple diagnostic
      approach and a diagram for decision making, based on clinical data and on
      urodynamic (cystoscopic and radiologic) findings. Various disorders can be
      associated; the treating physician, taking into account the patient's
      psychological status and behavioural disorders, must aid such support-seeking
      patients by careful listening, reinsurance and using simple methods of
      deconditioning and rehabilitation.

PMID- 7725036
TI  - [Rehabilitation of female urinary incontinence].
AB  - Perineal rehabilitation is an appropriate alternative to surgery in the treatment
      of urinary female incontinence. The most important factors influencing the
      success of this technique is the ability of the patient to identify correctly the
      muscles of the pelvic floor, to strengthen this muscles using exercises,
      electrical stimulation and biofeedback, to contract voluntarily the pelvic floor
      musculature during stress or sensation of voiding for having a preventive effect
      on loss of urine, and also to change, if necessary, the micturitional and
      drinking customs. Some conditions are required to complete a good result: strong
      motivation of the woman, ability of the physiotherapist or the midwife, quality
      of care and follow-up of the physician who must clearly know the place of this
      conservative treatment in selected patients, particularly in moderate stress
      incontinence, without important prolapse, urge incontinence, pregnancy and post
      partum, two conditions in which this technique must have a preventive and
      curative efficiency.

PMID- 7725037
TI  - [Surgical indications in female urinary incontinence].
AB  - In addition to artificial urinary sphincters, the surgical management of female
      urinary incontinence includes many surgical procedures of the bladder neck: its
      retropubic placement within the confines of abdominal pressure, posterior support
      preventing effort opening or the reduction of its diameter. Whatever the surgical
      procedure, surgical indications depend on discomfort and patient desire after
      complete assessment to evaluate risk of failure and postoperative complications.
      Choice of a technique depends on the surgeon's individual preference; success
      rate varies from 50 to 80% after 5 years follow-up.

PMID- 7725038
TI  - [Vesico-sphincter disorders of nervous origin].
AB  - Neurogenic bladder is a common feature in many neurological disorders such as
      stroke, multiple sclerosis, paraplegia, Parkinson disease, peripheral neuropathy.
      Specific treatment is always necessary to improve quality of life and decrease
      renal potential risk. Urodynamic investigations (cystometry, pelvic floor
      electromyography) are very useful to determine physiopathologic mechanisms of
      bladder dysfunction.

PMID- 7725039
TI  - [Medical treatment of disorders of the bladder sphincter].
AB  - A lot of drugs can increase or decrease bladder activity or urethral sphincter
      activity. Some of them are used for treatment of incontinence or chronic
      retention. In case of severe pollakiuria or urge incontinence secondary to
      bladder instability, numerous medications can be used: anticholinergic agents,
      musculotropic relaxants, calcium antagonists, prostaglandin inhibitors, beta
      adrenergic agonists, tricyclic antidepressants. Anticholinergic agents are
      regularly used on first choice. When stress incontinence is present, alpha
      agonists administered with estrogen and perineal reeducation represent the first
      stage before surgery. For medical treatment of retention, if there is not outlet
      obstruction, one can increase detrusor activity with betanechol chloride. In case
      of outlet obstruction, alpha-blockers or 5 alpha-reductase inhibitors can be
      used, if there is benign prostatic hyperplasia. Pygeum africanum can be used, but
      to date there is no clinical study proving its efficacy.

PMID- 7725040
TI  - [Sickle cell anemia. Physiopathology and diagnosis].

PMID- 7725041
TI  - [Hemoptysis. Diagnostic orientation].

PMID- 7725042
TI  - [Venous access. Techniques, complications].

PMID- 7725044
TI  - [Dyspnea. Diagnostic orientation].

PMID- 7725045
TI  - [Cancer of the thyroid gland].

PMID- 7725043
TI  - [Angiotensin-converting enzyme inhibitors. Principles and rules of use].

PMID- 7725046
TI  - [Work accidents and occupational diseases. Definition, role of the practitioner].

PMID- 7725047
TI  - [Towards the prevention of chronic diseases].

PMID- 7725048
TI  - [The general criteria and recommendations for the elaboration of programs for the
      early detection of breast cancer and cervical cancer in Spain. The Working Group
      for the Early Detection of Breast Cancer and Cervical Cancer].
AB  - Cancer screening and primary prevention of cancer are effective strategies to
      reduce cancer morbidity and mortality. The experience gained in several European
      countries about breast and cervical cancer has been growing in the last decades.
      This fact facilitates the adoption of the most convenient strategies to implement
      screening programmes in Spain. The Spanish Ministry of Health and Consumer
      Affairs set up a work group of experts and health managers to make
      recommendations and to define the basic criteria to take into account when
      planning and implementing these programmes. The article describes those
      recommendations as well as the priorities to be established regarding the target
      population, and the strategies to increase efficiency of those programmes.
      Recommendations were made according with scientific evidences and the current
      situation and resources in Spain.

PMID- 7725049
TI  - [The utilization of a hospital emergency service].
AB  - BACKGROUND: The use of the emergency room of a hospital during a year has been
      studied, in the last few years, the use of hospital emergency rooms has increased
      alarmingly, and a large number of patients come by their own initiative. With
      regard to this problem, we have considered it adequate to carry out this survey,
      in order to know the situation of hospital emergency rooms in our community.
      METHODS: We carry out a retrospective study from an aleatory representative
      sample of patients, cared during a year (from June, 1987 to June 1988) in the
      hospital emergency room of a health area in Asturias. RESULTS: Frequentation was
      116 per a thousand inhabitants a year and old-aged population constituted the
      largest number of people using this unit. The largest inflow of patients took
      place at 12 to 14 hours. Men came with a significant higher frequency than women.
      More than a half of patients came upon their own initiative. The percentage of
      justified admissions and emergencies was significatively higher among the
      patients sent by a doctor than among those ones who came by their own initiative,
      an it was higher when the doctor belonged to a Health Care Center, compared with
      doctors belonging to the traditional model. CONCLUSIONS: There exists a high
      index of non-justified emergencies and the hospital is used as a Primary Health
      Care center.

PMID- 7725050
TI  - [The effect of the socioeconomic level on the lipid pattern in children and
      adolescents].
AB  - BACKGROUND: The aim of this study was to evaluate the association between
      socioeconomic status and the presence of cardiovascular risk factors in children
      from Madrid. METHODS: We studied 2224 boys and girls, ages 2-18 years, attending
      five different school centers. They were divided into three socioeconomic groups:
      low class, middle-low class and middle high class, in regard to their parent's
      occupation and educational attainment. The evaluation included a blood analysis
      of serum triglycerides (TG), total cholesterol (CT), low density lipoprotein
      cholesterol (LDL), high density lipoprotein cholesterol (HDL), apolipoprotein A1
      (ApoA), apolipoprotein B100 (Apo B), and the Apo A/Apo B and LDL/HDL ratios.
      RESULTS: There was a positive correlation between socioeconomic status and total
      cholesterol, Apo A, Apo B and Apo A/Apo B, whereas socioeconomic status and
      triglycerides were inversely related. The LDL/HDL ratio varied according to age.
      CONCLUSIONS: Unlike some previously published studies, we found that children
      belonging to high socioeconomic status have a more atherogenic lipid profile than
      those of middle low or low socioeconomic levels.

PMID- 7725051
TI  - [Guidelines for the elaboration of programs for the primary prevention of
      cardiovascular diseases. The Working Group for Primary Cardiovascular
      Prevention].
AB  - This paper, elaborated by consensus between experts from Scientific Societies and
      the Health Administration, is aimed at providing general guidelines for the
      elaboration and prompting of cardiovascular disease primary prevention
      programmes, through individual risk factors screening and control. It is expected
      to be helpful for primary care professionals. After reviewing the rationale and
      logistics of the programmes starting in the Spanish context, an outline for the
      risk screening and assessment of the individuals attending the health services is
      set out. The strategies for high risk individuals control and the periodic health
      examination of low risk subjects are developed, emphasizing the multifactorial
      approach. Lastly operational criteria for the management of each risk factor
      taking simultaneously into account the whole risk picture, embracing definition
      criteria and consensus recommendations, are stated.

PMID- 7725053
TI  - [Health promotion policies].

PMID- 7725054
TI  - [An analysis of the potential years of life lost to cancer in Asturias and
      Spain].
AB  - BACKGROUND: Potential years of life lost (PYLL) constitute a health indicator,
      used to study premature mortality. If applied, it produces an order in causes of
      death, which can be very different from that one, obtained with mortality rates.
      METHODS: Mortality, due to different pathologies, was analyzed with this
      indicator and, particularly, mortality due to cancer in Asturias and Spain. The
      estimation of (PYLL) was made using fixed age limits: the first anniversary, as
      the lowest limit, and 65 years, as the highest limit. RESULTS: Cancer happened to
      be the first cause of (PYLL) in both populations (286,473 PYLL in Spain; out of
      them 9,985 belonging to Asturias); road accidents were the second cause (139,673
      and 4,755 respectively) and acute myocardium infarcts were the third cause
      (70,106 PYLL and 2,897 PYLL). Lung tumours, leukaemias and breast cancer in women
      are the malignant tumours which produce the highest number of PYLL. CONCLUSIONS:
      Malignant tumours, road accidents and ischaemic heart disease are the three major
      causes responsible for the PYLL production in Spain and Asturias. These three
      pathologies are associated to well known risk factors, whose disappearance would
      considerably reduce early mortality. Likewise, an excess of premature mortality
      is observed in Asturias compared with Spain, and in men compared with women.

PMID- 7725052
TI  - [The Canadian Heart Health Initiative: from policy to putting into practice].

PMID- 7725055
TI  - [The competence and skills of the family physician in ophthalmology].
AB  - BACKGROUND: In order to facilitate interprofessional collaboration and continuing
      education, it is necessary to define the family doctor (FD) work profile in
      ophthalmology and that this profile is accepted by FD and specialized doctors.
      METHODS: A questionnaire with 42 activities and 18 skills, belonging to the scope
      of ophthalmology was sent to 20 ophthalmologists in the Health Area of Pamplona.
      They were asked to value each item and to express whether they thought it
      belonged to the FD activity scope. The answers from 16 specialized doctors are
      compared with the answers from 16 FD. RESULTS: 30 activities and 12 skills are
      considered to be a part of the FD scope by 75% of them, compared with 22
      activities and 10 skills accepted by the ophthalmologists. More that 75% of these
      ones express their disagreement with three activities: identification of
      traumatic wounds in both cameras, surveillance of eye-pressure in patients at
      risk, surveillance of chronic glaucoma and early care of wounds in the eye globe;
      and in three skills: valuation of iridocorneal angle, enlargement of the eye
      pupil and verification of lacrimal conduct permeability. In 9 items,
      statistically significant differences were found (p 0.05) between both groups
      answers. Among them, the examinations and surveillance of retinopathies in
      vascular and metabolic diseases, stands out. CONCLUSIONS: Our study shows a
      disparity of positions, which may raise difficulties to the interprofessional
      collaboration between both groups. It is recommended to study the factors, which
      might have an influence on this disagreement. The elaborated list constitutes a
      progress in the definition of FD profile in ophthalmology, although it would be
      necessary to carry out more studies.

PMID- 7725058
TI  - [The Victoria Declaration: a call to action].

PMID- 7725057
TI  - [The International Colloquium on the Econometrics of AIDS].

PMID- 7725056
TI  - [Nosocomial infection and its impact on the stay in a neonatal intensive care
      unit (1988-1991)].
AB  - BACKGROUND: Neonatal intensive care units show one of the highest frequencies of
      nosocomial infections (NI), specially in teaching hospitals. METHODS: The
      cumulative incidence and distribution of NI in a neonatal intensive care unit of
      a teaching hospital during three years and three months (536 children) is
      studied, evaluating the relation between NI and its risk factors with X2 and
      variance analysis and, finally, estimating the excess stays with a multiple
      linear regression. RESULTS: The global cumulative incidence of NI was 11% (or an
      incidence density of 30.7 per 100 children/month); the prevailing etiological
      agents were negative coagulase Staphylococcus and fungi of Candida Sp. When
      analyzing, according to the kind of infection, sepsis associated to catheter,
      stands out. The relation between the different intrinsic or extrinsic risk
      factors and the NI was studied as well, and it stood out that infected children
      suffer manipulations as: Central catheter, assisted respiration, parenteral
      feeding et cetera, with a greater frequency (twice as much) that of non infected
      children. CONCLUSIONS: The cumulative incidence of NI is moderate-low; but is is
      necessary to continue insisting and increasing the current control measures and
      on the other hand, is is necessary to calculate the excess stays, due to NI, with
      multivariate methods because the direct estimation produces an overestimation of
      that one.

PMID- 7725059
TI  - [The Victoria Declaration. Closing the gap: science and policy in action. The
      Advisory Board of the International Conference of Cardiovascular Health].

PMID- 7725060
TI  - Local T-cell proliferation and differentiation in inflammatory myopathies.
AB  - Our objective was to investigate the patterns of proliferation and
      differentiation of infiltrating cells in inflammatory myopathies.
      Immunohistochemical staining was performed on muscle biopsy specimens from 18
      patients with inclusion body myositis, polymyositis and dermatomyositis using
      monoclonal and polyclonal antibodies. An abundance of cells were TNF-alpha+ (4
      8%), ICAM-1+ (7-65%), IFN-gamma+ (3-6%), and Ki-67+ (4-8%). It was shown that 70%
      of the Ki-67+ cells were Ki-67+CD3+ cells. Very few mononuclear cells were IL
      2R+. MHC-I expression was found on nearly all muscle fibres in all cases, while
      MHC-II expression was found on occasional muscle fibres in 1/3 of cases. Analysis
      of repeated biopsies from four IBM patients after prednisolone treatment showed
      no change in the proportions of TNF-alpha, ICAM-1, IFN-gamma or Ki-67 positive
      cells. In inflammatory myopathies there is an intense proliferation and
      differentiation of inflammatory cells in situ, indicating a local stimulation of
      the inflammatory process.

PMID- 7725061
TI  - Placental thrombosis and fetal loss after passive transfer of mouse lupus
      monoclonal or human polyclonal anti-cardiolipin antibodies in pregnant naive
      BALB/c mice.
AB  - In the present study we evaluated the effect of passive transfer of a mouse
      monoclonal (CAM) or a human polyclonal anti-cardiolipin IgG on pregnancy outcome
      in BALB/c mice. The mice were immunized through the tail vein immediately after
      mating with 10 micrograms of monoclonal or polyclonal anti-cardiolipin
      antibodies. Two other groups of mice were given a mouse irrelevant monoclonal
      antibody or normal human polyclonal IgG respectively, at the same dose. In mice
      immunized with monoclonal or polyclonal anti-cardiolipin antibody we observed a
      significant increase in the number of fetal resorptions and a significant
      reduction of the mean weights of the embryos and the placentas. In mice immunized
      with CAM we also found a significant decrease in the number of healthy pups,
      while mice infused with human aCL antibody expressed a significant reduction in
      the fecundity rate. The histological examination showed widespread thrombosis and
      necrosis in the placentas derived from the mice immunized with the anti
      cardiolipin antibodies. The model supports a possible direct pathogenetic effect
      of anti-phospholipid antibodies in recurrent fetal loss and points out that
      thrombotic events at placental level can be instrumental in the pathogenesis of
      the obstetric complications.

PMID- 7725064
TI  - S. typhi vaccine strain Ty21a can cause a generalized infection in whole body
      irradiated but not in hydrocortisone-treated mice.
AB  - Various mutations including galE- in the S.typhi vaccine strain Ty21a are thought
      to prevent proliferation of these micro-organisms in the host, and elimination of
      Ty21a would occur independent of the immune system of the host. To investigate
      this issue, we determined whether Ty21a can proliferate in immunosuppressed mice,
      and assessed the role of phagocytes in the eradication of Ty21a from tissues.
      Mice were rendered lymphocytopenic and monocytopenic by hydrocortisone s.c., or
      were made leucocytopenic by whole body irradiation. Bacteria were injected into a
      tail vene to evaluate eradication from the blood, liver and spleen, and into
      thigh muscle, i.e. a tissue that lacks resident macrophages. Ty21a were grown
      overnight in glucose [glu], or galactose and glucose [gal.glu]; only the Ty21a
      [gal.glu] expressed somatic O-antigens. After i.v. injection of 10(4) to 10(6)
      micro-organisms, Ty21a were rapidly eliminated from the liver and spleen of
      normal and immunosuppressed mice, i.e. within 1 day a 95% reduction of bacterial
      counts was observed. After i.m. injection of 10(4) to 10(6) bacteria, the number
      of viable Ty21a decreased in normal and hydrocortisone-treated mice, but in
      irradiated mice the micro-organisms proliferated and caused generalized
      infection. In all cases, Ty21a [glu] was eliminated more rapidly than Ty21a
      [gal.glu], confirming reports that killing of bacteria that lack O-antigens is
      more rapid than that of smooth bacteria of the same species. These results
      indicate that elimination of the vaccine strain against typhoid fever, Ty21a,
      from host tissues is not due to an intrinsic property of the micro-organisms that
      prevents proliferation but instead depends on the action of resident macrophages
      and exudate monocytes and granulocytes.

PMID- 7725062
TI  - Characterization of the gene encoding the MPB51, one of the major secreted
      protein antigens of Mycobacterium bovis BCG, and identification of the secreted
      protein closely related to the fibronectin binding 85 complex.
AB  - The secreted protein MPB51 is one of the major proteins in the culture filtrate
      of Mycobacterium bovis BCG (BCG) and is a protein immunologically cross-reacting
      with the fibronectin binding 85 complex secreted by this bacterium. The gene
      encoding MPB51 (mpb51) was cloned, sequenced, and expressed in Escherichia coli.
      The mpb51 gene was mapped downstream of the gene for 85A component with 179 bp
      spaces. The mpb51 gene encoded 299 amino acids, including 33 amino acids for the
      signal peptide, followed by 266 amino acids for the mature protein with a
      molecular mass of 27807.37 Da. This is the first complete sequence of MPB51.
      MPB51 showed 37-43% homology to the components of 85 complex. Two-dimensional
      electrophoresis of culture fluids of BCG and Western blotting indicated the
      existence of the other novel protein(s) which strongly cross-reacted with the
      alpha antigen (85B) and MPB51.

PMID- 7725063
TI  - Inhibition of complement-mediated red cell lysis by immunoglobulins is dependent
      on the IG isotype and its C1 binding properties.
AB  - We have investigated the effect on complement activation of human immunoglobulins
      (Ig) using several therapeutic Ig preparations including two for intravenous use
      (IVIG), and various purified myeloma proteins. Ig inhibited lysis in a dose
      dependent manner in the classical pathway assay whereas no alternative pathway
      inhibition was observed. The Fc part of the molecule was responsible for all the
      inhibitory effect. Purified IgG3 myeloma proteins were potent inhibitors whereas
      IgG1 inhibited to a lesser extent and IgG2 and IgG4 did not inhibit at all.
      Inhibition was obtained both when Ig was added to the solution and when it was
      coated onto a solid matrix. Analysis of the soluble and solid phase Ig after
      incubation revealed binding of C1q and activated C4 and C3 to the isotypes which
      inhibited lysis. Using selectively depleted sera and reconstitution with their
      respective purified components, efficient inhibition of lysis was seen when Ig
      was added prior to serum (C1), some inhibition was seen at the C4 level, whereas
      no effect was seen when Ig was added at the C9 level. We conclude that the
      complement-modulatory effect of Ig in vitro is isotype specific and dependent
      mainly on competitive C1 binding by the Ig molecule in the absence of antigen.

PMID- 7725065
TI  - Interleukin-10 directly inhibits the interleukin-6 production in T-cells.
AB  - IL-6 is a potent regulator of T-cell activation, proliferation and
      differentiation. Since IL-10 inhibits cytokine production by T cells, the effect
      of IL-10 on IL-6 production by T cells was investigated. IL-6 production by
      purified monocytes or T cells was detected from cell-free culture supernatants by
      ELISA after stimulation of the cells with LPS or an anti-CD3 monoclonal antibody
      for 3 days. Although the main source of IL-6 are LPS activated monocytes (29.6 +/
      10 ng/ml), T cells secreted sufficiently high levels of IL-6 (790 +/- 200 pg/ml)
      to stimulate the high affinity IL-6 receptor. IL-10 decreased anti-CD3 induced IL
      6 mRNA expression by up to 80%. In addition, IL-10 significantly inhibited IL-6
      release from T-cells. Highly purified, anti-CD3 activated T-cells secreted 600 +/
      150 pg/ml IL-6 compared to 21 +/- 2 pg/ml IL-6 following addition of IL-10 (10
      ng/ml; P < 0.001). FACS analysis revealed a monocyte contamination of the T-cell
      preparations of less than 0.5%. In addition, no IL-1 production was detectable.
      Thus, in our experiments the effect of IL-10 on IL-6 production was independent
      of the presence of monocytes. Finally, inhibition of IL-6 production was not
      reversed by IL-2 (100 U/ml). In conclusion, IL-10 suppressed the synthesis of IL
      6 by T-cells via a monocyte- and IL-2-independent mechanism. These results may
      help to understand the complex regulation of T-cell mediated cytokine production
      by IL-10.

PMID- 7725066
TI  - Impaired antigen-specific B-cell response and altered splenic microstructure in
      mice following continuous administration of IL-4 in vivo.
AB  - The effect of long term in vivo administration of IL-4 on the induction of
      antigen-specific B cells, the splenic microenvironment and the yield of antigen
      specific antibody producing hybridomas was studied. Immunization with DNP-KLH,
      followed by 12 weeks continuous IL-4 treatment resulted in increased numbers of
      total splenic (non-DNP) IgM and IgG AFC (antibody forming cells) on day 5 after
      booster, whereas the DNP-specific IgG and IgG1 AFC were reduced compared to age
      matched control animals not treated with IL-4. In addition, an almost 300-fold
      increase in non-DNP IgE was found while the IgE anti-DNP response was minimal.
      When the splenic cells were used in a fusion protocol, a relative decrease in
      yield of antigen-specific hybridomas was found in the long term IL-4 treated
      mice. Immunohistological staining of spleen sections from mice treated with IL-4
      up until the time of booster revealed reduced B-cell follicle area and germinal
      centre numbers. These results show that extensive IL-4 treatment reduced antigen
      specific B-cell formation and suggests a reduction in the number of B cells
      entering the memory B-cell pathway in the spleen.

PMID- 7725067
TI  - The identification of germinal centres and follicular dendritic cell networks in
      rheumatoid synovial tissue.
AB  - We document here the identification of germinal centres with dark and light
      zones, a follicular dendritic cell network and clonal expansion in the synovium
      of rheumatoid arthritis patients. Synovial tissue from 24 patients suffering from
      rheumatoid arthritis or the polyarticular form of juvenile rheumatoid arthritis
      were screened for the presence of lymphoid follicles. The synovial tissues of 14
      patients contained follicles and four of these had germinal centres and a
      follicular dendritic cell network. There was a statistically significant
      association between follicles in the synovium and the presence of rheumatoid
      factor autoantibodies in the patients' serum indicating a link between local
      germinal centre formation and the presence of pathological rheumatoid factors.
      Nucleotide sequencing of monoclonal rheumatoid factors from one of the patients'
      synovial tissue which contained germinal centres clearly supports the possibility
      that these rheumatoid factors have gone through a germinal centre reaction. While
      rheumatoid factors from healthy immunized donors are regulated through a
      tolerization mechanism which selects against replacement mutations and does not
      allow affinity maturation, synovial rheumatoid factors seem to lack this
      tolerization mechanism. The formation of germinal centres where B cells affinity
      mature and expand at the central site of disease in rheumatoid arthritis may
      explain why rheumatoid factors in rheumatoid arthritis develop into auto
      aggressive antibodies.

PMID- 7725068
TI  - V beta-specific activation of T cells by the HIV glycoprotein gp 160.
AB  - Studies by several groups have suggested that HIV infection in vivo results in a
      V beta-specific alteration of the TCR repertoire and that this might play a role
      in the pathogenesis of AIDS. However, there is very little agreement as to which
      V beta segments are affected. In order to circumvent the confounding factors
      present in vivo we have examined the abilities of both a crude protein extract of
      HIV and purified gp160 to alter the V beta repertoire of normal T cells in vitro.
      We find that both a crude extract of HIV as well as gp160 specifically activate T
      cells expressing a common set of V beta segments (V beta 3, 12, 14, 15, and
      sometimes V beta 17 and 20) in individuals of disparate HLA type. This set of V
      beta segments is remarkably similar to those recognized by staphlococcal
      enterotoxin B and supports the hypothesis that bacterial superantigens produced
      by opportunistically acquired micro-organisms could have an exacerbating effect
      in AIDS.

PMID- 7725069
TI  - Identification of two distinct function gamma delta TCR complexes on the surface
      of a human T cell clone.
AB  - In this study we describe the expression of two T cell receptor (TCR) gamma
      chains on the surface of a human T cell clone isolated from the peripheral blood.
      Each gamma chain was part of an independent and functional TCR. The dual receptor
      T cell clone (and all subclones derived from this clone) had stable expression of
      this phenotype. Immunoprecipitation studies revealed the expression of non
      disulfide linked TCRs by this V gamma 4+V gamma 9+V delta 1+ T cell clone, which
      was in agreement with the finding that both V gamma gene transcripts were
      rearranged to C gamma 2-associated joining elements. Both gamma chains were
      derived from productive rearrangements of different (allelic) genes coding for a
      V gamma 4+ and a V gamma 9+ gamma-chain, and both were coupled to a V delta 1+
      delta chain. Incubation of this V gamma 4+V gamma 9+V delta 1+ T cell clone with
      TCR gamma-chain-specific MoAbs rapidly induced an increase in intracellular Ca++,
      indicating that both gamma-chains are functional. Furthermore, this clone
      responded to stimulation with S. aureus derived superantigens. We suggest
      therefore that exogenous (super)antigens can trigger dual receptor T cells
      resulting in activation of these T cells.

PMID- 7725070
TI  - T lymphocytes bearing the gamma delta T cell receptor are susceptible to steroid
      induced programmed cell death.
AB  - The mechanisms by which glucocorticoids suppress immune responses have not yet
      been clearly defined. In steroid-sensitive pathological conditions, an increase
      in gamma delta T cells can occur in certain untreated systemic autoimmune
      disorders and seems to be a peristent feature in most cases of systemic lupus
      erythematosus (SLE). Our previously published data demonstrated that
      immunosuppressive therapy normalized this expanded SLE T cell subset in parallel
      with clinical remission of the symptoms. To establish how corticosteroid
      treatment determines the disappearance of peripheral blood gamma delta T
      lymphocytes, circulating alpha beta and gamma delta T lymphocytes from seven SLE
      subjects with active disease and seven healthy individuals were cultured in the
      presence or absence of 10(-7) M Dexamethasone (DEX). Cell suspensions were then
      analysed for DNA fragmentation, characteristic of apoptotic cell death, by a new
      cytofluorimetric method. Conventional agarose-gel electrophoresis on the same T
      cell populations was carried out for comparison. Regular follow-ups for 6 months
      revealed in vivo steroid treatment determined a dramatic fall in SLE blood gamma
      delta T cells, and in vitro experiments seem to indicate that DEX-triggered
      apoptotic signals are confined to the double negative (CD4-CD8-) gamma delta T
      cell subpopulation which disappears after in vivo immunosuppressive therapy.
      Clinical and pathological remission of some autoimmune diseases is often obtained
      by corticosteroids. Our results offer new insights on the mechanisms through
      these hormones exert their potent inhibitory activities on immune system cells
      postulated to play a role in the generation of autoimmune responses.

PMID- 7725071
TI  - The distribution and abnormal morphology of plasma cells in rheumatoid synovium.
AB  - This study assessed the distribution and structural features of plasma cells in
      rheumatoid synovial tissue. Plasma cells were found to be the predominant
      infiltrating mononuclear cells (mean 40%) in relation to lymphocytes and
      monocytes, and there was a direct relationship between their number in the
      infiltrates and the total number of mononuclear leucocytes (P = 0.007). Plasma
      cells were also seen in intimate contact with macrophages intermixed with
      synovial lining cells, and closely associated with small blood vessels. They
      often surrounded these blood vessels and sometimes were seen lying within the
      vessel walls themselves. Ultrastructural analysis revealed that many synovial
      plasma cells were considerably larger than plasma cells of a normal size and
      possessed a marked distension of the cisternae of rough endoplasmic reticulum.
      Furthermore, plasma cells in close proximity to blood vessels often appeared to
      be undergoing migration. These observations imply that in rheumatoid synovium,
      plasma cells are metabolically very active and occupy a pivotal position for the
      secretion of antibodies into both the vascular and the extravascular
      compartments.

PMID- 7725072
TI  - Visual search at different spatial scales.
AB  - Treisman and Gelade's (1980) feature-integration model claims that the search for
      separate ("primitive") stimulus features is parallel, but that the conjunctions
      of those features require serial scan. Recently, evidence has accumulated that
      parallel processing is not limited to these "primitive" stimulus features, but
      that combinations of features can also produce parallel search. In the
      experiments reported here, the processing of feature conjunctions was studied
      when the stimulus features of a combination were at different spatial scales. The
      patterns in the search array were composed of three cross-shaped or T-shaped
      (local) elements, which formed an oblique bar (the global pattern) 45 deg or 135
      deg in orientation. When the target and distractors differed from each other at
      one spatial scale only (either in the bar orientation or in the shape of the
      local elements), target detection was independent of the number of distractors,
      i.e., the search was parallel. In the conjunction task, in which the target and
      distractors were defined as the combinations of the bar orientation and the
      element shape, i.e., both spatial scales were relevant, the detection of the
      target required slow serial scrutiny of the search array. It is possible that the
      conjunction search could not be performed in parallel because switches between
      the two scales (or spatial frequency channels) are linked to attention and the
      task required the use of both scales in order to find the target.

PMID- 7725073
TI  - Acculturative stress among young immigrants in Norway.
AB  - The study examined the relationship between migration and the incidence of
      emotional disorders among 568 young Third World immigrants in Norway.
      Participants were 10-17 years of age. Using a questionnaire, acculturative stress
      (i.e., change in health status as a result of acculturation) was found to exist
      among the children, although having to migrate or being born in Norway was not
      related to mental health status. A stressful acculturative experience (i.e.,
      difficulties in initiating friendship with Norwegian peers) alone could account
      for only 1% of the self reported emotional disorders. Incidence of depressive
      tendencies, poor self image, and psychological and somatic symptoms were found to
      be related to close and supportive parents, marginality, integration, gender and
      the number of friends the child had. These accounted for between 12 and 15% of
      the explained variance. The paper theoretically discusses how these factors may
      be related to acculturative stress, and recommends them as starting points for a
      primary intervention program to reduce emotional disorders among these children.

PMID- 7725074
TI  - Risk perception and the location of a repository for spent nuclear fuel.
AB  - This study investigates lay people's reactions to a repository for nuclear waste.
      Risk perception is seen as a complex concept, comprising both affective and
      cognitive components. Attitude towards nuclear power and trust in experts and
      authorities had a substantial impact on risk perception, while personal knowledge
      about nuclear waste disposal had no effect. Thus, the more positive one's
      attitude towards nuclear power is and the more trust one has in experts and
      authorities, the lower one's risk perception is. Also, reactions were expected to
      vary with distance between the home district and the location of a repository.
      These variations differed in nature for people with alternative levels of risk
      judgement. The distance between the home and a repository affected approval of
      the proposed site. Distance between home and repository also had an effect on
      risk feelings and somewhat less on beliefs about consequences. Estimated total
      risk was directly mediated by beliefs about consequences, but even more so by
      risk feelings. With regard to risk, one can conclude that it is important to make
      a distinction between an emotional and a cognitive component of risk perception.

PMID- 7725075
TI  - Memory in schizophrenia and affective disorders.
AB  - The purpose of the present study was to investigate the stability of memory and
      information processing in schizophrenics and affectively disturbed patients.
      Twenty-two schizophrenics, eight affectives and 14 normal controls were tested
      twice, with an interval of approximately one year. Results showed that normals
      performed better than schizophrenics and affectively disturbed patients on almost
      all of the cognitive measures. The differences reached a level of significance on
      a reaction time test, a vigilance task and a long-term memory task. The only
      measure where the difference did not reach a level of significance was on a short
      term memory test. Groups' performance to some extent changed over time on most of
      the measures, but the changes were not significantly different for different
      groups.

PMID- 7725076
TI  - To drive or not to drive: neuropsychological assessment for driver's license
      among stroke patients.
AB  - Seventy-two stroke patients, 43 with right hemisphere (RHD) and 29 with left
      hemisphere damage (LHD), and 7 coronary infarct controls with no evidence of
      cerebral damage, were neuropsychologically tested as part of an assessment
      program for driver's license. Mean age in the group was 53 years. Stroke patients
      were tested on average 4 months post injury. The groups did not differ on major
      demographic variables except that RHD patients were more often hemiplegic than
      LHD patients. The test battery was factor analyzed into 4 valid principal
      components: (I) visual perception, (II) spatial attention, (III) visuospatial
      processing, and (IV) language/praxis. The presence of hemianopia (factor I)
      excludes driving. In addition, measures of neglect and reduced speed of mental
      processing from factor II, III and IV, were found to be the most discriminating
      variables when classifying patients for driving. Even though neglect was more
      frequently observed among RHD than LHD patients, the two hemisphere groups did
      not differ significantly in number of patients denied driving, 58% RHD compared
      to 41% LHD patients. The need for comprehensive neuropsychological assessment is
      underlined.

PMID- 7725077
TI  - Determinants of word fragment completion.
AB  - A current debate in the memory literature concerns the validity of word fragment
      completion (WFC) as a test of implicit memory. It has been claimed that language
      variables exert a strong influence on the task, and that the task reflects memory
      only to a small extent (Hintzman & Hartry, 1990). For these reasons, the use of
      contingency analyses of recognition and WFC performance as a means of studying
      underlying memory processes has been criticized. The present study addressed this
      issue by examining the influence of language variables on completion of a set of
      computer generated single-solution fragments of Swedish words (Olofsson & Nyberg,
      1992). It was found that language variables indeed had a large effect on
      completion performance, and that priming only accounted for a small portion of
      variance in the task. It is therefore suggested that the method of triangulation
      should be employed for contingency analyses involving WFC.

PMID- 7725078
TI  - The empirical relationships of the religious orientations to personality.
AB  - The aim of this study was to investigate the relationships between the religious
      orientations and the psychoanalytic character types, as assessed by the Basic
      Character Inventory (BCI). A person with an intrinsic religious orientation is
      sincere and integrated in his religiousness. A person with an extrinsic religious
      orientation uses his religion to promote his personal, social and economic goals.
      A person with a quest religious orientation is seeking, doubting and changeable
      in his religiousness. In a sample of 471 subjects, 168 men and 303 women, the
      level of intrinsic religious orientation was not related to the BCI scores. The
      levels of extrinsic and quest religious orientations were positively related to
      the BCI Oral score. Since the oral persons are dependent and craving, it seems
      likely that they may be extrinsically oriented. And as they also may be insecure,
      vague and indecisive, it is not unexpected that they also are quest oriented. The
      changeable quest orientation was also positively related to the changeable BCI
      Hysterical character.

PMID- 7725079
TI  - Inducible enterobacterial responses to environmental pollution by sodium ions and
      alkalinisation.

PMID- 7725080
TI  - Possible function of the cytoplasmic axial filaments in chromosomal segregation
      and cellular division of Escherichia coli.
AB  - Expression of the cafA gene at 71 min on the E. coli chromosome map by use of a
      high copy number expression vector caused (1) overproduction of the 51 kDa CafA
      protein, (2) formation of chains of normal cells and shorter anucleate cells, and
      (3) formation of flexible, tough structures, which we call 'cytoplasmic axial
      filaments', running throughout the centre of the chained cells. In this article
      we shall describe the morphology, physiology and possible functions of the
      cytoplasmic axial filament structure. This structure could be a strong candidate
      for one of the procaryotic cytoskeletal/cytokinetic elements functioning in
      cellular extension and division, chromosomal segregation and other important
      mechanisms involved in the proliferation of procaryotic cells.

PMID- 7725081
TI  - Photodynamic therapy.

PMID- 7725082
TI  - Hair trace element analysis in human ecology studies.
AB  - Concentrations of Zn, Cu, Se, Mn, Hg, Fe, Cr, Co, Sb, Sc and Au were determined
      in hair samples of 17 ethnic and territorial groups from the former USSR. Hair
      samples (837 males, 965 females) were taken from individuals of non-industrial
      native populations of unpolluted areas. Geographical, geochemical, racial and
      nutritional aspects of inter-group variations of trace element concentrations are
      discussed. The significance of hair analysis as a biological indicator of
      abnormal intake of trace elements in man is confirmed. Geographical variations of
      hair trace element concentrations, on the whole, depend on geochemical conditions
      or nutritional factors. The concentration of elements in hair is highly variable
      because of local factors, which makes racial or ethnic identification impossible
      for trace element analysis.

PMID- 7725083
TI  - Chemical forms of gamma-emitting radionuclides in soils adjacent to the Chernobyl
      NPP.
AB  - Samples of sandy forest soils, meadow sandy-peat soil and meadow sandy-loam soil
      were taken at different sites within a 30-km zone around the Chernobyl NPP
      (ChNPP). The samples were extracted with water and a 0.1-N solution of ammonium
      acetate. The extracts were measured for gamma-radionuclides and stable cation
      content. The content of all mobile forms of the radionuclides present in the 0-10
      cm soil layer accounts for 0.5-5% of the total radionuclide content in this
      layer, depending on the type of radionuclide and soil. Water soluble forms of the
      radionuclides were found in the 0-5-cm layer only. Exchangeable radionuclide
      forms were represented, as a rule, by radiocaesium in both the 0-5- and 5-10-cm
      layers. Content of Cs-137 exchangeable forms in the organic-mineral horizon were
      roughly inversely proportional to the sum of stable exchangeable cations and
      organic matter content. Forest vegetation takes up a significant share of the
      mobile forms of radiocaesium from the soils.

PMID- 7725084
TI  - Paint as a source of recontamination of houses in urban environments and its role
      in maintaining elevated blood leads in children.
AB  - A detailed lead isotopic and scanning electron microscope investigation of
      particulates from three houses in urban Sydney, previously decontaminated by
      their owners, has shown that they have been recontaminated over varying periods,
      as short as 6 months. The source of recontamination is lead paint from adjoining
      dwellings whose paint is thoroughly deteriorated, as well as from unknown
      sources. In one house, the external to internal lead loading was > 10:1. The
      pathway for the lead paint contaminants is both airborne and mechanical transport
      into the houses. Recontamination of houses provides an explanation for the
      maintenance of elevated blood lead levels in the children residing in these
      houses. Recontamination can be a major urban problem applicable in any community
      which used leaded paints on dwellings in the past. It is a matter of concern for
      families with young children and couples, especially women who are, or intend to
      become, pregnant.

PMID- 7725085
TI  - On the potential of molecular computing.

PMID- 7725086
TI  - On the potential of molecular computing.

PMID- 7725087
TI  - On the potential of molecular computing.

PMID- 7725088
TI  - U.K. panel weighs tissue ownership.

PMID- 7725089
TI  - Companies fear FDA rule on antibodies.

PMID- 7725090
TI  - Multiple 'SIDS' case ruled murder.

PMID- 7725091
TI  - Old dates for modern behavior.

PMID- 7725092
TI  - NASA's space biology program shows signs of life.

PMID- 7725093
TI  - A boom in plans for DNA computing.

PMID- 7725094
TI  - Catching fly balls: a new model steps up to the plate.

PMID- 7725095
TI  - Functions of the proteasome: the lysis at the end of the tunnel.

PMID- 7725096
TI  - From the cradle to the grave: ring complexes in the life of a protein.

PMID- 7725097
TI  - Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A
      resolution.
AB  - The three-dimensional structure of the proteasome from the archaebacterium
      Thermoplasma acidophilum has been elucidated by x-ray crystallographic analysis
      by means of isomorphous replacement and cyclic averaging. The atomic model was
      built and refined to a crystallographic R factor of 22.1 percent. The 673
      kilodalton protease complex consists of 14 copies of two different subunits,
      alpha and beta, forming a barrel-shaped structure of four stacked rings. The two
      inner rings consist of seven beta subunits each, and the two outer rings consist
      of seven alpha subunits each. A narrow channel controls access to the three inner
      compartments. The alpha 7 beta 7 beta 7 alpha 7 subunit assembly has 72-point
      group symmetry. The structures of the alpha and beta subunits are similar,
      consisting of a core of two antiparallel beta sheets that is flanked by alpha
      helices on both sides. The binding of a peptide aldehyde inhibitor marks the
      active site in the central cavity at the amino termini of the beta subunits and
      suggests a novel proteolytic mechanism.

PMID- 7725098
TI  - DNA solution of hard computational problems.
AB  - DNA experiments are proposed to solve the famous "SAT" problem of computer
      science. This is a special case of a more general method that can solve NP
      complete problems. The advantage of these results is the huge parallelism
      inherent in DNA-based computing. It has the potential to yield vast speedups over
      conventional electronic-based computers for such search problems.

PMID- 7725099
TI  - Dating and context of three middle stone age sites with bone points in the Upper
      Semliki Valley, Zaire.
AB  - The extent to which the earliest anatomically modern humans in Africa exhibited
      behavioral and cognitive traits typical of Homo sapiens sapiens is controversial.
      In eastern Zaire, archaeological sites with bone points have yielded dates older
      than 89(-15)+22 thousand years ago by several techniques. These include electron
      spin resonance, thermoluminescence, optically stimulated luminescence, uranium
      series, and amino acid racemization. Faunal and stratigraphic data are consistent
      with this age.

PMID- 7725100
TI  - A middle stone age worked bone industry from Katanda, Upper Semliki Valley,
      Zaire.
AB  - Three archaeological sites at Katanda on the Upper Semliki River in the Western
      Rift Valley of Zaire have provided evidence for a well-developed bone industry in
      a Middle Stone Age context. Artifacts include both barbed and unbarbed points as
      well as a daggerlike object. Dating by both direct and indirect means indicate an
      age of approximately 90,000 years or older. Together with abundant fish
      (primarily catfish) remains, the bone technology indicates that a complex
      subsistence specialization had developed in Africa by this time. The level of
      behavioral competence required is consistent with that of upper Paleolithic Homo
      sapiens sapiens. These data support an African origin of behaviorally as well as
      biologically modern humans.

PMID- 7725101
TI  - Crystal structure of DCoH, a bifunctional, protein-binding transcriptional
      coactivator.
AB  - DCoH, the dimerization cofactor of hepatocyte nuclear factor-1, stimulates gene
      expression by associating with specific DNA binding proteins and also catalyzes
      the dehydration of the biopterin cofactor of phenylalanine hydroxylase. The x-ray
      crystal structure determined at 3 angstrom resolution reveals that DCoH forms a
      tetramer containing two saddle-shaped grooves that comprise likely macromolecule
      binding sites. Two equivalent enzyme active sites flank each saddle, suggesting
      that there is a spatial connection between the catalytic and binding activities.
      Structural similarities between the DCoH fold and nucleic acid-binding proteins
      argue that the saddle motif has evolved to bind diverse ligands or that DCoH
      unexpectedly may bind nucleic acids.

PMID- 7725102
TI  - Masking of the CBF1/RBPJ kappa transcriptional repression domain by Epstein-Barr
      virus EBNA2.
AB  - Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) is a transcriptional activator
      that is essential for EBV-driven B cell immortalization. EBNA2 is targeted to
      responsive promoters through interaction with a cellular DNA binding protein, C
      promoter binding factor 1 (CBF1). A transcriptional repression domain has been
      identified within CBF1. This domain also interacts with EBNA2, and repression is
      masked by EBNA2 binding. Thus, EBNA2 acts by countering transcriptional
      repression. Mutation at amino acid 233 of CBF1 abolishes repression and
      correlates with a loss-of-function mutation in the Drosophila homolog Su(H).

PMID- 7725103
TI  - Expression cloning of a protective Leishmania antigen.
AB  - Parasite-specific CD4+ T cells have been shown to transfer protection against
      Leishmania major in susceptible BALB/c mice. An epitope-tagged expression library
      was used to identify the antigen recognized by a protective CD4+ T cell clone.
      The expression library allowed recombinant proteins made in bacteria to be
      captured by macrophages for presentation to T cells restricted to major
      histocompatibility complex class II. A conserved 36-kilodalton member of the
      tryptophan-aspartic acid repeat family of proteins was identified that was
      expressed in both stages of the parasite life cycle. A 24-kilodalton portion of
      this antigen protected susceptible mice when administered as a vaccine with
      interleukin-12 before infection.

PMID- 7725104
TI  - How baseball outfielders determine where to run to catch fly balls.
AB  - Current theory proposes that baseball outfielders catch fly balls by selecting a
      running path to achieve optical acceleration cancellation of the ball. Yet people
      appear to lack the ability to discriminate accelerations accurately. This study
      supports the idea that outfielders convert the temporal problem to a spatial one
      by selecting a running path that maintains a linear optical trajectory (LOT) for
      the ball. The LOT model is a strategy of maintaining "control" over the relative
      direction of optical ball movement in a manner that is similar to simple predator
      tracking behavior.

PMID- 7725105
TI  - Potentiated necrosis of cultured cortical neurons by neurotrophins.
AB  - The effects of neurotrophins on several forms of neuronal degeneration in murine
      cortical cell cultures were examined. Consistent with other studies, brain
      derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 all attenuated
      the apoptotic death induced by serum deprivation or exposure to the calcium
      channel antagonist nimodipine. Unexpectedly, however, 24-hour pretreatment with
      these same neurotrophins markedly potentiated the necrotic death induced by
      exposure to oxygen-glucose deprivation or N-methyl-D-aspartate. Thus, certain
      neurotrophins may have opposing effects on different types of death in the same
      neurons.

PMID- 7725106
TI  - In vivo functional analysis of the Ras exchange factor son of sevenless.
AB  - The Son of sevenless (Sos) protein functions as a guanine nucleotide transfer
      factor for Ras and interacts with the receptor tyrosine kinase Sevenless through
      the protein Drk, a homolog of mammalian Grb2. In vivo structure-function analysis
      revealed that the amino terminus of Sos was essential for its function in flies.
      A molecule lacking the amino terminus was a potent dominant negative. In
      contrast, a Sos fragment lacking the Drk binding sites was functional and its
      activity was dependent on the presence of the Sevenless receptor. Furthermore,
      membrane localization of Sos was independent of Drk. A possible role for Drk as
      an activator of Sos is discussed and a Drk-independent interaction between Sos
      and Sevenless is proposed that is likely mediated by the pleckstrin homology
      domain within the amino terminus.

PMID- 7725107
TI  - Proteasome from Thermoplasma acidophilum: a threonine protease.
AB  - The catalytic mechanism of the 20S proteasome from the archaebacterium
      Thermoplasma acidophilum has been analyzed by site-directed mutagenesis of the
      beta subunit and by inhibitor studies. Deletion of the amino-terminal threonine
      or its mutation to alanine led to inactivation of the enzyme. Mutation of the
      residue to serine led to a fully active enzyme, which was over ten times more
      sensitive to the serine protease inhibitor 3,4-dichloroisocoumarin. In
      combination with the crystal structure of a proteasome-inhibitor complex, the
      data show that the nucleophilic attack is mediated by the amino-terminal
      threonine of processed beta subunits. The conservation pattern of this residue in
      eukaryotic sequences suggests that at least three of the seven eukaryotic beta
      type subunit branches should be proteolytically inactive.

PMID- 7725108
TI  - Herpes-like sequences in HIV-infected and uninfected Kaposi's sarcoma patients.

PMID- 7725109
TI  - Building an associative memory vastly larger than the brain.

PMID- 7725110
TI  - Neutrophils and drug metabolism.

PMID- 7725111
TI  - Thumbs, tools, and early humans.

PMID- 7725112
TI  - Thumbs, tools, and early humans.

PMID- 7725113
TI  - Thumbs, tools, and early humans.

PMID- 7725114
TI  - Incentives can lower the incidence of HIV/AIDS in Africa.

PMID- 7725115
TI  - Health and social sciences in Sri Lanka. An overview of the Triangle Programme.
      Introduction.

PMID- 7725116
TI  - Protective measure use and symptoms among agropesticide applicators in Sri Lanka.
AB  - Sri Lankan farmers use large amounts of pesticides to control the pests affecting
      their vegetable crops. Improper use of pesticides by farmers has resulted in
      poisoning of occupational origin. This paper examines the use of protective
      measures by pesticide applicators and its relationship to their illness symptoms.
      The data were collected by interviewing a stratified random sample of 150 farmers
      from predominantly vegetable growing areas of the Matale district during 1990/91
      using structured questionnaires. These data were supplemented with secondary data
      and observation of all stages of pesticide application. Scales were constructed
      to measure the domains of material style of life, awareness and use of protective
      measures, and illness symptoms experienced by pesticide applicators. It was found
      that most of the farmers were aware of the protective measures to be used when
      applying pesticides. There was, however, no significant positive relationship
      between awareness and use of protective measures. The main reason for not using
      protective measures was discomfort. The most common symptoms reported by
      pesticide applicators were faintish feeling, headache and dizziness. A
      significant negative relationship was observed between use of protective measures
      and symptoms exhibited within four hours of application. It is recommended that
      protective materials adapted to the climate and socio-economic conditions of
      farmers be developed, and that farmers be encouraged to use these protective
      materials through appropriate educational efforts and incentives.

PMID- 7725117
TI  - Health and social status of an elderly urban population in Sri Lanka.
AB  - Although Sri Lanka has generally a young demographic profile, with decreasing
      overall mortality and birth rates, its population is aging gradually and will
      continue to do so in the future. In order to have an idea of the needs of the
      elderly a survey was conducted in a sample of randomly selected Sinhalese elders
      living in an urban community. Activities of Daily Living (ADL) and Instrumental
      Activities of Daily Living (IADL) assessments were done. Ten percent of the
      respondents had at least one ADL impairment. Another ten percent had only IADL
      impairment. The commonest ADL to be affected were bathing and feeding. Children
      and the family provide all care for the impaired elderly. The family support
      system should be encouraged and assisted to prevent the necessity for more formal
      and expensive institutional care. A large proportion of the elderly were
      handicapped with defects in vision and hearing and the absence of teeth.
      Correction of these defects would improve both quality of life of these subjects
      and reduce their risk of accidents.

PMID- 7725118
TI  - First trimester feeding in a rural Sri Lankan population.
AB  - One hundred Sinhalese mothers with infants at three months age in a rural
      population in Central Sri Lanka were interviewed by questionnaire on the feeding
      of their infants from birth to 3 months of life. 96% of babies were being breast
      fed at 3 months age. However, 32% have already been started on formula. Of this
      32, eight mothers were from poor families receiving state subsidies. 20 of the 32
      were giving expensive formulas made by multinational companies, (including four
      of the eight mothers receiving state subsidies and feeding formula) in spite of
      the availability of cheap comparable state subsidized formulas. In rural Sri
      Lanka only about a quarter have access to drinking water but 96% were giving
      water or other weak nutritional solutions at 3 months of age. 72% were using
      bottles for feeding. 77% were being given sugar and, 13% salt through non-milk
      solutions while 11% were getting sugar through their formula. Maternal
      employment, increasing maternal age, less than sixteen hours of maternal contact
      time per day with child, delay in initiation of breast feeding after birth were
      all significantly associated with a higher risk of formula feeding. A lower birth
      order and early initiation of breast feeding after birth were associated with a
      higher risk of babies being fed on non-milk solutions. In the light of these
      findings it is suggested that the time is now opportune for the National
      Nutritional Programme to shift its present emphasis from the promotion of breast
      feeding in these (and similar) areas to the promotion of exclusive breast feeding
      in the early infant's diet, while discouraging formulas, non-milk solutions,
      weaning foods, salt, sugar and the use of the bottle as a feeding utensil.

PMID- 7725119
TI  - Heart specialists' art of care.
AB  - Primary care physicians who encourage patients to interact in the medical
      interview receive high ratings of patient satisfaction with art of care. To
      determine if this finding holds true in specialty medicine, we designed a two
      factor [art of care (high/low); heart specialty (cardiology/cardiovascular
      surgery)] four-group analogue study. Videotapes for each of the four conditions
      depicted the first interview between (actor) patient with coronary artery disease
      and (actor) specialist. The high art of care physicians elicited the patient's
      story in his own words and encouraged questions and feedback during the
      interview; the low art of care physicians did not encourage patient interaction.
      The cardiologists discussed medical treatment and the cardiovascular surgeons
      discussed surgical treatment. A pilot study of the instrument we developed
      indicated that the Art of Care Scale, Technical Quality of Care Scale, and
      Willingness to be Treated Scale demonstrated high internal consistency and that
      the Art of Care Scale and the Technical Quality of Care Scale defined two
      dimensions. In the final study, 124 graduate students in education in a
      midwestern United States university each viewed one videotape and used the
      instrument to evaluate the physician. Subjects rated the specialists who
      encouraged patients to interact higher on the Art of Care Scale than specialists
      who did not encourage interaction. Art of Care Scale Scores predicted subjects'
      willingness to be treated by the physician they viewed on the videotape. No
      significant differences in ratings of Art of Care could be attributed to
      specialty.

PMID- 7725120
TI  - Researching public health: behind the qualitative-quantitative methodological
      debate.
AB  - Debates about appropriate methodologies for studying public health problems have
      tended to be polarized. Traditionalists, advocating the use of epidemiology and
      other methods drawn from a reductionist research tradition have tended to devalue
      the potential contribution of more interpretive research methods. Those
      advocating the use of more qualitative methods have often established the
      legitimacy of these methods by criticising the contribution of quantitative
      techniques. These debates often mask more fundamental differences in epistemology
      and approaches to dealing with the issues of power raised by research which aims
      to be compatible with the philosophy of the new public health. This paper argues
      that these underlying issues are crucial to contemporary public health debates
      and the methods are simply tools that are used to further knowledge and have no
      inherent status as sound or unsound. Public health problems result from complex
      social, economic, political, biological, genetic and environmental causes. A
      range of methods are needed to tackle these and public health researchers are
      most effective when they are eclectic in their choice of methods.

PMID- 7725121
TI  - Heavy users of emergency services: social construction of a policy problem.
AB  - A relatively small subgroup of emergency department (ED) patients is responsible
      for a disproportionate amount of ED visits and costs. This subgroup, the heavy
      users of ED services, is identified as a medically and socially vulnerable
      population. Heavy users of ED services are identified as a 'problem' in the
      United States that opens a 'window' on the wider social issues critical to
      consensus on health care reform. The problem is nested within a complex of
      larger, interdependent problems including access to care, lack of
      primary/preventive services, absent or inadequate social services, and fragmented
      service delivery. This article uses the literature on heavy users of ED services
      to argue that social constructions of the problem and articulation of solutions
      by different key players in health care reform are based on divergent and often
      conflicting premises.

PMID- 7725122
TI  - Quality of life of 125 adults surviving 6-18 years after bone marrow
      transplantation.
AB  - BACKGROUND: Recent studies examining the medical and psychosocial sequelae of
      bone marrow transplantation have reported most survivors do relatively well while
      a smaller group continues to experience less than optimal quality of life (QOL).
      Many of these studies are limited by small sample sizes, limited scope, and focus
      on a narrow (1-4 year) window of survival. METHODS: The descriptive survey
      examined the QOL, late medical complications, psychological distress, demands of
      long-term recovery, and health perceptions of 125 adults surviving 6-18 (mean 10)
      years after marrow transplantation. Seven wide-ranging tests covering 271 items
      were completed on average in 90 min. Two tests were developed by the authors
      specifically for assessing QOL in this population. RESULTS: 74% of long-term
      survivors of bone marrow transplantation reported their current QOL was the same
      or better than before transplantation, 80% rated their current health status and
      QOL as good to excellent, and 88% said the benefits of transplantation outweighed
      the side effects. Ten years or more post-transplantation, long-term survivors
      continued to experience a moderate incidence of lingering complications and
      demands, including emotional and sexual dysfunction, fatigue, eye problems, sleep
      disturbance, general pain and cognitive dysfunction. However, the severity or
      degree of distress attributed to those complications was, for most survivors,
      consistently low. Nearly all were back to work or school. Only 5% rated both
      their QOL and health status as poor. Long-term survivors demonstrated good mood
      and low psychological distress compared to cancer and population norms, and had
      the same perceptions as the general population of their current health and
      expectation of future health. Demands attributed to long-term survival appeared
      to impose little hardship. The most frequently cited demand of recovery was the
      perceived lack of social support as time went on. CONCLUSIONS: Almost all long
      term survivors were leading full and meaningful lives. Persistent complications
      were, on the whole, dismissed as relatively trivial and the overwhelming majority
      viewed themselves as cured and well.

PMID- 7725123
TI  - Why do women report 'sick building symptoms' more often than men?
AB  - The prevalence of general, mucosal and skin symptoms compatible with the 'Sick
      Building Syndrome' (SBS) was studied in Swedish office workers. The marked excess
      in symptom prevalence among females, 12% SBS cases as compared to 4% among males,
      was analysed with respect to differences in biological or acquired risks and
      different illness and reporting (interview) behaviour among males and females.
      The distribution of risk indicators for symptoms was recorded in a questionnaire
      to 4943 employees. The skin symptom questions were validated in a clinical
      examination. Most risk indicators, such as paper work and psychosocial work load,
      had an unfavourable distribution for females. In the multivariate analysis
      however, female sex remained the most prominent risk indicator almost unaffected
      by the addition of other factors. Neither did effect modification contribute to
      the excess prevalence among females. The results from the clinical examination
      indicate that the excess symptom prevalence among females is real and not a
      reporting artefact. As the factors studied did not explain the excess symptom
      prevalence among females, the sex differential observed can be a reflection of a
      general excess of psychosomatic symptoms among women. Although inequalities in
      social conditions did not substantially explain the sex differential in symptom
      reporting, the importance of life situation and social roles should be further
      explored. As the studied variables are surrogates for actual measurements,
      another important issue is whether sex differences in working conditions,
      entailing different hierarchical positions in the office, have consequences for
      indoor air quality factors that are important for the symptoms. The study
      strongly underlines the importance of taking the sex distribution into account
      when surveying risk indicators for SBS symptoms.

PMID- 7725124
TI  - The experience of an AIDS prevention program focused on South African traditional
      healers.
AB  - A national HIV/STD prevention program focused on traditional healers was started
      in South Africa in late 1992. An initial group of 28 healers (the 'first
      generation') was trained in HIV/AIDS and STD prevention. These 28 in turn trained
      a total of 630 additional healers (the 'second generation') in formal, week-long
      workshops within seven months of the first workshop (this figure grew to 1510
      healers by the end of the tenth month). This paper reports results of an
      assessment of the impact of training during the first seven months of the
      program. The second generation appeared to be as well trained as the first, if we
      can rely on measures such as reporting correctly how HIV is transmitted and how
      HIV transmission can be prevented. Healers also reported advising their patients
      to use condoms, and demonstrating methods of correct condom use. Healers were
      initially recruited through national, formal associations of traditional healers,
      of which there are several in South Africa. Yet several months into the program,
      healers were critical of donor groups working with and through such associations.
      Most preferred that membership in such associations not be a prerequisite for
      participation in donor group-supported collaborative programs. The present
      program accordingly began to explore the possibility of recruiting healers
      through existing, indigenous associations of diviner-mediums known as impandes.

PMID- 7725125
TI  - A problem solving intervention for caregivers of cancer patients.
AB  - Effects of a psychosocial intervention program on spouses of cancer patients, and
      on the cancer patients themselves, will be described. A six session intervention
      program, which included support, problem-solving and coping skills, was designed
      to help spouses to cope with the stress of caring for their partner. Forty male
      and forty female spouses of cancer patients of a regional oncology center were
      randomly assigned to intervention or usual treatment conditions. Spouses and
      patients were interviewed prior to intervention, and within two weeks after
      intervention on a battery of assessment instruments including: (1) demographic
      variables; (2) psychological variables; (3) health status; (4) social supports;
      (5) assessment of pressing problems; (6) coping skills; (7) burden levels; and
      (8) marital satisfaction. Participants were found to be more psychologically
      distressed than the general population but were not as distressed as psychiatric
      outpatients. Differences were also found in marital satisfaction and coping
      activities, when compared to the general population. No significant differences
      between the conditions were found on any of the measures. Caregivers' level of
      caregiving activities proved to be low. It is suggested that this may account for
      why the intervention only appeared effective for a distressed subsample of the
      caregivers in the study. The implications of these findings is discussed.
      Recommendations are also made for future research on cancer caregivers.

PMID- 7725126
TI  - The strategy of risk approach in antenatal care: evaluation of the referral
      compliance.
AB  - The main goal of antenatal care in developing countries is to identify women
      whose pregnancy or delivery is likely to raise problems and to refer them at the
      appropriate time to a hospital facility where the necessary medical equipment and
      expertise (vacuum extractors, cesarian sections, human skill, etc.) is available.
      This approach, which is known as the Risk Approach (RA) strategy, is expected to
      significantly reduce maternal morbidity and mortality. However, the RA will
      function properly only if the women identified at risk agree to give birth in a
      hospital on the one hand, and if they can indeed reach this hospital on the other
      hand. In this article the authors assess to what extent women with a risk of
      difficult labor (nulliparous or primiparous women under 150 cm, history of
      previous difficult delivery or stillbirth, women with transverse lie) agreed to
      give birth in a hospital. This descriptive survey, which covered 5060 pregnancies
      monitored in the Kasongo District, Maniema, in eastern Zaire, showed that the
      referral success rate in this socioeconomically very disadvantaged region was
      only 33%, despite some favorable conditions, such as a strong emphasis on
      community participation, a complementarity of health centers and hospital, and
      the absence of financial barriers within the health services system. Of the
      various hypotheses tested, the geographic accessibility of the hospital and the
      parturient's perception of the risk status were the two most important factors
      determining the compliance rate. A stratified analysis shows that the intensity
      of the parturient's perception has a different impact on compliance whether rural
      or urban situations are considered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725128
TI  - Directness and deference in pharmacy students' messages to physicians.
AB  - The profession of pharmacy is in the midst of an attempted role expansion.
      Advocates of a philosophy of practice known as pharmaceutical care want to expand
      the traditional role of the pharmacist to include patient counseling, drug use
      monitoring, clinical consultation with physicians, and responsibility for patient
      outcomes. Other health professions are resisting this role expansion, and it has
      proven difficult to socialize students into a professional role that is not yet
      widely accepted. To better prepare students for the workplace, pharmacy educators
      need a way of assessing the extent to which students have accepted and begun to
      enact the expanded clinical role. Since role and identity disputes are negotiated
      in routine interactions between pharmacists and other health professionals, an
      assessment tool was devised to mimic a common interprofessional interaction.
      Written messages to physicians were gathered from pharmacy students in response
      to a hypothetical drug allergy scenario. Pharmacist-physician communication is
      especially problematic because many of the acts pharmacists routinely perform
      (e.g. correcting, reminding, reporting, etc.) are intrinsically threatening to a
      physician's professional identity and sense of self worth. Brown and Levinson's
      politeness theory explains how situational factors influence peoples' choices in
      dealing with such identity threatening acts. As an act becomes more threatening,
      the degree of politeness accompanying the act also increases. Detailed content
      analysis of pharmacy students' messages to physicians determined that allergy
      reports were more likely to be made directly than alternative drug
      recommendations. Recommendations were more likely than reports to be omitted
      entirely. Implications for pharmacy students' emerging professional identities
      are discussed.

PMID- 7725127
TI  - Appearance-based information about coping with pain: valid or biased?
AB  - Previous research led to the conclusion that patient characteristics such as
      physical attractiveness and non-verbal expressiveness affected judgements of
      patient pain and distress. This study investigated whether this represents an
      intrusive bias or whether there indeed are psychological differences between
      physically attractive vs physically unattractive and expressive vs inexpressive
      pain patients. The findings led to the conclusion that both variables are related
      to the types of coping strategies pain patients use. Specifically, physically
      attractive and nonverbally expressive patients were found to be less likely to
      utilize passive coping strategies. Coping style also was found to be related to
      demographic characteristics of the patients. Theoretical reasons for the
      identified relationships are discussed as are the implications of these findings
      for the assessment of pain.

PMID- 7725129
TI  - Role orientation and community pharmacists' participation in a project to improve
      patient care.
AB  - Community pharmacists are being assigned increased responsibility in assuring the
      appropriateness and effectiveness of drug therapy. This increased responsibility
      is reflected in recently passed legislation (OBRA '90) in the United States that
      requires pharmacists to counsel patients about prescriptions received and to
      engage in prospective drug use review for Medicaid recipients. The potential
      impact of this legislation is unclear due to a dearth of research evaluating the
      effects of community pharmacists' activities on medication use. In addition,
      there is little research on pharmacists' willingness to assume increased
      responsibility. Research that would demonstrate the effectiveness of community
      pharmacists in improving therapeutic outcomes is hampered by problems inherent in
      conducting experimentally designed research in field settings. This paper
      examines two issues of concern in such studies--namely, the extent to which those
      who agree to participate in a demonstration project differ from those who decline
      to participate and the extent to which differential dropout from treatment and
      control conditions compromise the comparability of the two groups. Specifically,
      this report examines pharmacist characteristics related to participation in a
      demonstration project to improve the care of elderly patients. Community
      pharmacists in Florida who had earlier been asked to participate in a
      demonstration project (N = 418) were sent mail questionnaires to assess their
      attitudinal, demographic and employment characteristics. In particular,
      researchers were interested in the role orientation of pharmacists in regard to
      patient counseling and physician consultation, satisfaction with current jobs and
      career choices, employment settings and treatment vs control group assignment as
      predictors of participation in the research project. Demographic characteristics
      were also examined as possible predictors of participation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7725131
TI  - [24 hours at the Mobile Emergency and Resuscitation Service].

PMID- 7725130
TI  - Psychosocial and medical factors in pregnancy outcomes: a case study of Israeli
      women.
AB  - Building on a body of research which confirms that psychosocial factors have an
      important influence on health in general and on pregnancy outcomes in particular,
      we carried out a prospective study of pregnant women in Israel. We hypothesized
      that medical pregnancy and delivery outcomes are mediated by psychosocial coping
      resources and risks. Resources were defined as social ties, and risks as life
      events self-reported as stressful. The population studied included 233 women who
      responded to questionnaires after the second trimester of pregnancy. Medical data
      on the delivery were collected from hospital archives. The questionnaire measured
      biomedical risks, including general medical and obstetrical history, as well as
      health behaviours, social ties, and perceived stress. Pregnancy outcomes were
      classified according to medical measures of abnormalities in mother and child at
      birth. Our findings show that resources such as the variety of social ties
      (family, friends, neighbours and colleagues) interacted significantly with
      biomedical risk. It was found that low scores for social ties anticipated 3.6
      times higher negative medical outcome in otherwise healthy women than in those
      with higher scores for social ties. The findings of the study are discussed in
      terms of their implications for relating to social competence as a determining
      element in health and health behaviour.

PMID- 7725132
TI  - [The Mobile Emergency and Resuscitation Service at Eaubonne-Montmorency].

PMID- 7725133
TI  - [Collective emergency service].

PMID- 7725134
TI  - [The activities of teaching and training].

PMID- 7725135
TI  - [Mobile emergency and resuscitation service--intoxication. A smiling explanation
      of the passion for emergencies].

PMID- 7725136
TI  - [Prevention and treatment of bedsores. At each stage a precise therapeutic
      intervention and an adjusted nursing process].

PMID- 7725137
TI  - [The nurse at the Mobile Emergency and Resuscitation Service].

PMID- 7725138
TI  - [The Mobile Emergency and Resuscitation Service. Evolution and perspectives].

PMID- 7725139
TI  - [Cardio-respiratory arrest].

PMID- 7725140
TI  - [Thrombolysis].

PMID- 7725141
TI  - [Childbirth at home].

PMID- 7725143
TI  - [Purpose and risks].

PMID- 7725142
TI  - [History of emergency medical services].

PMID- 7725144
TI  - [Unstable blood products. Establishment of their traceability].

PMID- 7725145
TI  - [Is the patient the beneficiary of the practice of confidentiality?].

PMID- 7725146
TI  - [The neuroleptics. Methods of use and contraindications].

PMID- 7725147
TI  - [Medical regulations].

PMID- 7725148
TI  - [Fixation of tubules with radioactive technetium dimercaptosuccinate in
      parenchymal diseases of the kidney].
AB  - In order to evaluate tubular function 99mTc-DMS dynamic kidney scintigraphy and
      99mTc-DMS uptake determinations were performed in 55 patients with endemic
      nephropathy, diabetic nephropathy and glomerulo nephritis. From 64-656th segment
      of computerized radiorenograms 99mTc-DMS uptake and curve slope were assessed and
      compared with the corresponding parameters of 20 healthy subjects. Both
      parameters were decreased in patients of all three groups. Tubular uptake of
      99mTc-DMS measured during 60 sec. 4 hours after 99mTc-DMS administration, was
      decreased in endemic nephropathy and diabetic nephropathy, but without a
      significant difference in glomerulonephritic patients. The study of the
      relationship between 4 hour 99mTc-DMS tubular fixation and glomerular filtration
      rate, estimated by 99mTc-DTPA clearance, showed a positive correlation only in
      patients with diabetic nephropathy. Patients with renal failure from all three
      groups had more seriously impaired tubular handling of 99mTc-DMS, that correlated
      with reduction of the glomerular filtration rate. The present data showed more
      severe impairment of tubular function in patients with endemic nephropathy and
      diabetic nephropathy than in glomerulonephritic patients. The method was suitable
      for estimation of the tubular function.

PMID- 7725149
TI  - [Coronary arteries in the Macaca fascicularis monkey].
AB  - The coronary arterial epicardial network in the monkey Macaca fascicularis was
      studied. The study concerned 11 hearts of healthy and fertile animals of both
      sexes. The morphological and morphometric results of the studies performed by
      microdissection revealed that: In all examined cases of the Macaca fascicularis
      the heart was supplied by blood through the left and right coronary arteries. The
      left coronary artery had a larger external diameter (1.2 mm-2.5 mm, average 1.8
      mm) than the right one (0.7 mm-1.2 mm, average 0.9 mm). The left coronary artery,
      with the average length of 4.3 mm (1.8 mm-6.5 mm), usually (82%) ended by
      bifurcation in to the anterior interventricular and the circumflex branch, and
      less frequently (18%) by trifurcation forming, in this way, another branch: the
      left marginal branch. The anterior interventricular branch had the larger
      external diameter (0.9 mm-1.7 mm, average 1.3 mm) than the circumflex one (0.7 mm
      1.7 mm, average 1.1 mm). Most frequently (73%) it could be traced along the
      diaphragmatic cardiac surface. The circumflex branch usually (73%) terminated as
      the posterior interventricular branch, and less frequently (9%) as one of the
      right posterior ventricular branches. The long type of the right coronary artery
      was observed in 45% of the cases. The presence of the myocardial bridges over the
      branches of the left coronary artery was found in 54% of the examined hearts. The
      great resemblance between the Macaca fascicularis subepicardial network with the
      corresponding one in humans suggest that Macacus fascicularis is a suitable
      experimental animal for functional studies of the cardiovascular system.

PMID- 7725150
TI  - [Histologic manifestations in the skin in alpha-lactoalbumin intradermal tests in
      patients with chronic urticaria].
AB  - Intradermal injection with alpha-lactoalbumine, 2000 PNU/ml was carried out in
      seven patients (1 male, 6 females, mean age 32.4 years) suffering from milk
      intolerance. None of the patients had a positive allergen-specific IgE antibodies
      in the sera (RAST). Skin test was performed on the volar part of the forearms at
      the same time. The area of skin reaction was estimated and measured within 36
      hours on the right arm. Skin biopsy was done with a 4 mm punch after 8 hours from
      site of antigen injection on the left arm. Various cells infiltrating the site of
      antigen instillation were present. Leukocytoclastic vasculitis was only found in
      patients with dual intradermal reaction (immediate and late onset of response; 8
      12 hours). These results indicate that local skin reaction to alpha-lactoal
      bumine is mediated by diverse immune mechanisms, and that it may be of clinical
      significance for the diagnosis of cow milk allergy in adults.

PMID- 7725152
TI  - [Complications in secretory otitis media treated with aeration-drainage tubes].
AB  - Nine hundred and twenty aeration-drainage tubes were implanted in 500 patients
      suffering from secretary otitis media. Besides visible improvement of the hearing
      in 85% of operated ears, the importance of some sooner or later complications
      should be pointed out. Usually this is intraoperative haemorrhage (50%). However
      tube obstruction (8%) or perception deafness were not rare. The importance of
      myringosclerosis (35%), and of the elimination of implant (12%) is emphasised.
      The appearance of postimplantation cholesteatoma and many other sooner or later
      complications are also analysed. The basic principles of microsurgical technique
      for the prevention of complications are enumerated.

PMID- 7725151
TI  - [Use of pulsating high-frequency electromagnetic fields in patients with diabetic
      neuropathies and angiopathies].
AB  - High-frequency pulsating electromagnetic field therapy was carried out in 22
      patients with diabetic polyneuropathy and angiopathy manifested on lower
      extremities (18 men, 4 women, aged 48.2 +/- 6.3 years; 10 insulin-dependent
      persons, and 12 on oral antidiabetic treatment). The aim of the study was to
      verify the effect of this therapy on symptoms, neurophysiological findings and
      peripheral circulation. The diagnose of diabetic polyneuropathy was based on the
      electromyographic examination of foot and calf muscles, measurement of motor
      nerve conduction velocity of peroneal and tibial nerve, and sensory nerve
      conduction velocity of sural nerve. Diagnosis of diabetic polyneuropathy was
      based on electromyographic examination of the foot and calf muscles, measurement
      of the motor nerve conduction velocity of peroneal and tibial nerves, and the
      sensory nerve conduction velocity of the sural nerve. Diagnosis of diabetic
      angiopathy was established by oscillometric examination, measurement of skin
      temperature and claudication distance. The same methods were used for the
      evaluation of the therapeutical effect of electromagnetic field. Significant
      improvement of symptoms, and of all registered parameters of peripheral
      circulation was established after the therapy, but there were no significant
      changes of neurophysiological parameters. Therefore, high-frequency pulsating
      electromagnetic field is recommended for the treatment of diabetic angiopathy. In
      patients with neuropathic changes it can be used as an introduction procedure, or
      as an additional procedure to physical agents which are commonly used in the
      treatment of peripheral nerve lesion.

PMID- 7725153
TI  - [Arterial hypertension in patients with primary glomerulonephritis].
AB  - Arterial hypertension is a state of blood pressure permanently higher than 160/90
      mm Hg (21.3/12.6 kPa). The renal cause of hypertension occurs in about 10% of all
      cases. The aim of this article was to establish the frequency, the level, and the
      connection of the hypertension in different types of primary glomerulonephritis.
      In this study 90 patients with primary glomerulonephritis were observed.
      Hypertension was present in 45 patients (50%) and different frequency were
      noticed in different types of glomerulonephritis. The smallest frequency was
      recorded in the group with minimal changes and IgA nephritis. In the group with
      mesangioproliferative glomerulonephritis 52% of patients had hypertension and in
      the group with focal segmental sclerosis 78%. The most frequent hypertension was
      observed in the group with rapidly progressive glomerulonephritis. Renal failure
      was more frequent in patients with hypertension. Different frequencies of
      hypertension was established in different types of glomerulonephritis. It was not
      severe and was well controlled by remedies. In most cases it suggest a severe
      glomerular lesions and fast progression of the disease.

PMID- 7725154
TI  - [Is penicillin still the drug of choice in the treatment of diseases caused by
      beta-hemolytic streptococci?].
AB  - During the last ten years a new pathomorphosis of streptococci was noticed and
      described in the USA, Europe and New Zealand. It was expressed by the rise of
      virulence of beta haemolytic streptococci (BHS) and development of new clinical
      and epidemiological features. In such circumstances it appears to be very
      relevant to examine the susceptibility of BHS to penicillin, which is still
      considered as a drug of choice for the most of streptococcal diseases. Therefore
      it was decided: 1. to make an analysis of continuous susceptibility testing of
      BHS to penicillin and 2. to test the possibility of induction and selection of
      penicillin resistant mutants in vitro. Penicillin susceptibility was examined by
      broth dilution method Penicillin tolerant strains were separated on the basis of
      MBC/MIC ratio MBC/MIC > 16 and construction of "killing curves". The possibility
      of induction and selection of penicillin resistant mutants was tested by
      subcultivation technique. MIC values for BHS groups: A, B, C and G were: 0.015,
      0.060, 0.015 and 0.030 micrograms/ml respectively. The percentage of penicillin
      tolerant strains was in the range of 3% for group A BHS to 33% for group G BHS.
      After 60 subcultures in liquid medium containing increasing concentrations of
      penicillin. MIC values were raised by 2-32 times in comparison with parental
      strains. As the maximal induced MIC values were 1 and 2 micrograms/ml (one group
      G and three groups B BHS strains) it can be concluded that BHS at least in vitro
      expressed penicillin resistance. Although the obtained results are encouraging
      (there is so far no penicillin resistant clinical isolates), the increasing
      percent of penicillin tolerant strains and the possibility to induce penicillin
      resistance in vitro should be considered as a very serious warning. That makes
      further investigation of the development of penicillin tolerance and resistance
      mechanisms very current.

PMID- 7725155
TI  - [Temporary arterial occlusion and intraoperative monitoring of somatosensory
      evoked potentials during treatment of cerebral aneurysms].
AB  - Temporary occlusion of the main artery feeding aneurysm with intraoperative
      monitoring of somatosensitive evoked potentials was performed in 10 patients: in
      the majority of them because premature aneurysm rupture, and in 3 patients to
      facilitate the dissection of the aneurysm and application of a definitive clip.
      The duration of temporary occlusion was between 5 to 20 minutes. The basic
      changes of SEP abnormalities were manifested in the prolongation of absolute
      latencies and the central conduction time. The changes were reversible. One
      patient died 30 days after the operation from lung infection; the condition of
      one was unchanged; two patients with mental sequelae had good but long recovery;
      outcome in one patient was good and in the others it was excellent. Temporary
      occlusion may not have disastrous consequences, and it can be well tolerated if
      performed in a reasonable period of time. The SEP monitoring is helpful in the
      operative management of aneurysms showing early signs of ischaemia.

PMID- 7725156
TI  - [Chronic airway obstruction in allergic bronchial asthma].
AB  - In the group of 161 patients with allergic bronchial asthma, a chronic
      obstruction in the respiratory ways was diagnosed in 85 cases (52%), and
      reversible in 76 cases (48%). An unexpectedly high percentage of obstruction in
      the respiratory ways among the patients is interpreted as a result of continued
      or frequently repeated exposure to allergens, air pollution and respiratory
      infection. For prevalence of chronic obstruction in the airways it is important
      to reach an early diagnosis, preventive measures, an appropriate and everyday
      therapy, regular control of the lung function, as well as mutual cooperation of
      the patient and physician.

PMID- 7725157
TI  - [Miliary tuberculosis of the lungs].
AB  - The study concerned 37 adults patients with miliary tuberculosis, who were
      treated at the Institute for Lung Diseases and Tuberculosis in Belgrade, over the
      period from 1987 to 1990. This number of patients is 1.37% of the total number of
      hospitalized patients with TB. The average age was 51 yrs (21-78). The sex
      distribution was equal. Associated diseases and predisposing conditions existed
      in 28 (76%) patients, most often haematologic diseases, systemic diseases of the
      connective tissue, and alcoholism. Classical X-ray finding of the lungs was
      present in 89% of the patients, and poor and atypical in 11%. The accompanying
      pleural exudation was observed in 13.5% of the patients, smaller cavernae in
      5.4%, and enlarged mediastinal lymph nodes in one patient. The diagnosis of
      miliary TB was bacteriologically or pathohistologically confirmed in 31 (84%)
      patients, on autopsy in 2 cases and by antituberculotic test in 4 cases. Positive
      Loewenstein culture media were obtained in 62% of patients, from sputum in 64% of
      cases, in the liquor in 5.4%, and from the pleural fluid in 2.7% of patients. (BK
      was found by direct sputum microscopy in 6 pts - 16%). Positive pathohistological
      findings was obtained in 18 (49%) patients: by pleural biopsy in 2 cases, lung
      biopsy in 8 (bronchoscopy in 5 pts, aspiration needle biopsy in 2 pts), and by
      biopsy of extrathoracic tissues and organs in 8 pts. Early diagnosis was
      established in 62% patients.

PMID- 7725158
TI  - [The effect of body height, age, sex and cerebral hemisphere dominance on
      somatosensory evoked potentials induced by stimulation of the median nerve].
AB  - Spinal and cortical somatosensory evoked potentials (SEP) to median nerve
      stimulation were recorded in 72 healthy subjects (38 men, 34 women, aged 44.5 +/-
      9.4 years, height 172 +/- 7.9 cm), with the intention to establish the influence
      of age, height, sex and dominant hemisphere on the latencies of components N9,
      N13, P15, N20, P22, P40, and the N9-N13, P15-N20, P15-P22 and N13-N20 condition
      times (interpeak latencies). Significant correlation was found between the age,
      the height, and all registered SEP components. No significant correlation was
      found between conduction times and the height, with the exception of N9 N13
      conduction time. Significant correlation was found between the age, the sex, and
      N13-N20 conduction time. For the P15-N20 and P15-P22 conduction times,
      correlation with the age and sex was poor, and it did not exist for the N9-N13
      conduction time. Between the dominant and non-dominant hemisphere there were no
      significant differences in latencies of SEP components and conduction times.
      Therefore, the analysis of SEP components and conduction times, must concern the
      age, the height and the sex. Dominant hemisphere can be neglected because it has
      no influence on SEP components.

PMID- 7725159
TI  - [Emergencies in arterial hypertension in children].
AB  - From March 1982 to March 1992 at the Nephrology Department of Belgrade University
      Children's Hospital 25 patients (16 females and 9 males, aged from 1.5 to 14
      years) were treated for hypertensive emergency. Twenty patients had chronic
      severe hypertension of whom in 19 it was of renal origin. Five patients had acute
      hypertension during acute poststreptococcal glomerulonephritis. In 15 patients
      hypertensive emergency was manifested by neurologic disorders, while in the other
      patients signs of cardiac failure prevailed. Deterioration of renal function was
      observed in 9 patients and 2 had sec. haemolytic-uremic syndrome. Three patients
      died during hypertensive crisis, and the others were successfully treated. The
      fact that in 50% of patients chronic hypertension could not be revealed until the
      occurrence of hypertensive emergency, suggests the need of its early detection
      during systemic check-up.

PMID- 7725160
TI  - [Biologic effects and possible therapeutic use of the granulocyte-macrophage
      colony-stimulating factor. Modern treatment of leukopenia].
AB  - This review is a brief overview of recent advances in biology as well as in
      potential clinical application of recombinant human granulocyte-macrophage colony
      stimulating factor (rhGM-CSF). Biologically active rhGM-CSF is a recombinant
      human protein expressed in Escherichia coli. GM-CSF is produced by nontransformed
      (T-lymphocytes, trophoblasts, keratinocytes, osteoblasts, tracheal epithelial
      cells, renal mesangial cells, endothelial cells, macrophages, fibroblasts, smooth
      muscle cells) and transformed (murine plasmocytoma, bladder carcinoma HIBY cell
      line, anaplastic carcinoma of the gall bladder, Yoshida sarcoma cell line, HC3T3
      osteoblast cell line) cells. RhGM-CSF increases the number of circulating
      neutrophils, monocytes and eosinophils and increases chemotactic, microcidal
      killing and cytotoxic activity of monocytes and granulocytes. The present
      clinically relevant uses of rhGM-CSF two general areas: restoration of
      haematopoietic dysfunction by raising cell counts from suppressed to normal
      levels, and augmentation of host defence against infection. Thus, rhGM-CSF
      reduces risk of infections. In addition, rhGM-CSF may increase tumour cell
      destruction in some malignant diseases. RhGM-CSF produces dose-dependent toxicity
      consisting of myalgic fever, fluid retention and serosal effusions.

PMID- 7725162
TI  - [The erythrocyte sedimentation test (part 2)].
AB  - The article deals with progression in the knowledge about erythrocyte
      sedimentation, and factors responsible of their sedimentation. Problems in the
      interpretation of results are also emphasized, as well as relation between some
      diseases and erythrocyte sedimentation velocity. Test indications are enumerated.

PMID- 7725161
TI  - [Administration of intravenous immunoglobulins in adult patients with hematologic
      diseases].
AB  - Abnormalities in serum immunoglobulin levels or in antibody production may
      develop as a result of many different diseases. Antibody deficiency may occur in
      previously normal persons with haematologic malignancies or who received
      immunosuppressive agents in treatment of cancer or in anticipation of bone marrow
      transplantation. Effective regimens may develop in primary immunodeficiencies and
      secondary immunodeficiencies as well as in idiopathic thrombocytopenic purpura.
      Some reports and information about the other haematological indications were
      published in medical literature. However, the consensus conference on IVIG at the
      National Institutes of Health (Bethesda--May 21, 1990) recommended treatment with
      IVIG in haematology only for CLL, ITP and after bone marrow transplantation, as a
      prevention for GVHD. The adverse effects of IVIG therapy are minimal, but they
      exist. The other important subject is the cost of widespread use of IVIG;
      therefore the indications must be carefully concerned and documented before
      therapy is started.

PMID- 7725163
TI  - [Methods of whole body irradiation].
AB  - Total body irritation, the essential method of pretreatment of a patient for bone
      marrow transplantation has not yet been a routine practice in our radiotherapy
      centres. Basic components of total body irradiation methods are reviewed, because
      they should be considered as a background for the very first decision in the
      choice of a method and details of pretreatment of a patient facing bone marrow
      transplantation.

PMID- 7725164
TI  - [Aleksandar Dj. Kostic, a historical personality in Serbian medical science].

PMID- 7725165
TI  - [100 years since the death of Peter Illich Tschaikovsky (1840-1893)].

PMID- 7725166
TI  - [Experiences with an over 8-year MR and 15-year CT cooperation from general
      practice of the Passau clinic].

PMID- 7725167
TI  - [CT follow-up after transjugular intrahepatic portosystemic stent shunt (TIPSS)].

PMID- 7725168
TI  - [BOOP (bronchiolitis obliterans with organizing pneumonia) syndrome: value of
      high-resolution CT within the scope of clinical and radiologic diagnosis].

PMID- 7725169
TI  - [Contrast medium-induced renal structural changes in healthy and ill rats].

PMID- 7725170
TI  - [Changes in the spine with MRI and skeletal scintigraphy after supra- and
      infradiaphragmatic radiotherapy of patients with Hodgkin's disease].

PMID- 7725171
TI  - [Diagnosis and therapy of post-traumatic hemobilia].
AB  - The submitted case-history deals with a successfully diagnosed and treated case
      of post-traumatic hemobilia in a 13-year-old girl. Hemobilia was manifested
      clinically by the typical Sandblom triad of symptoms. It was due to a
      pseudoaneurysm of the peripheral arteriole of the hepatic artery diagnosed by
      selective liver angiography. In treatment selective intraarterial embolization of
      the supplying artery proved useful.

PMID- 7725172
TI  - [Adnexal torsion in childhood].
AB  - During the 7-year period (1987-1993) the authors treated nine girls on account of
      torsion of the adnexa. In six girls torsion of primarily unaltered adnexa
      occurred, in one girl torsion of an ovary enlarged by a cyst and in two torsion
      of the ovary affected with a benign tumour, a coetaneous teratoma. In seven
      instances the organ affected with ischaemic necrosis had to be resected. In two
      girls detorsion of the ovary was performed, according to a sonographic control
      examination, however, in one the affected ovary atrophied. In the discussion the
      authors deal with the diagnosis of torsion of the adnexa and the method of
      treatment. The authors consider ultrasonic examination of organs of the abdominal
      cavity and retroperitoneum a very suitable method in all cases of abdominal pain
      in childhood, as this method can greatly contribute to the diagnosis of acute
      abdominal and gynaecological attacks. During surgery they recommend to preserve
      adnexa with a doubtful vitality because there is certain hope that they will be
      saved. During the postoperative period they recommend the long-term follow up of
      girls clinically and by ultrasonographic checks. If pathological changes are
      detected on the preserved adnexa, they recommend early re-operation and
      elimination of the risk factor (cysts etc.). The operation should be supplemented
      by prophylactic fixation of the preserved adnexa if this fixation was not done
      already during the primary operation.

PMID- 7725173
TI  - [Use of heterotopic substitutes in the urinary bladder in children and adults].
AB  - Intestinal replacements of the urinary bladder are a solution of severe
      congenital damage of the lower urinary pathways also in young patients. The
      children tolerate the operation very well. Already at the age of four years they
      are able to cope with the catheterization of the stoma of the urinary reservoir.
      The continence of the lower urinary pathways contributes also considerably to
      improvement of the mental development of the child.

PMID- 7725174
TI  - [A non-traditional procedure in the surgical treatment of portal hypertension in
      a child].
AB  - The authors present the case-history with a uncommon surgical procedure in a
      child with portal hypertension and hypersplenism. Half the spleen was resected
      and concurrently a distal splenorenal anastomosis of the Warren type was created.
      This procedure was selected because the child had a very enlarged spleen and
      marked hypersplenism. The postoperative course was free from complications and
      the satisfactory condition of the child 15 months after operation with normal
      haematological values confirms the justification of the selected procedure.

PMID- 7725175
TI  - [Comparison of the results of conservative and surgical therapy of dislocated
      supracondylar fractures of the humerus in children].
AB  - The authors evaluate retrospectively in a group of 121 children with a dislocated
      supracondylar fracture in 1984-1993 the results of different therapeutic methods.
      The highest percentage of excellent and satisfactory results was recorded in
      children treated by closed reposition with percutaneous pinning with Kirschner
      wires (88%). In open reposition with Kirschner wires 60% of the results were
      excellent of satisfactory. The lowest percentage of excellent and satisfactory
      results was recorded when fixation with a plaster bandage was used (48%). The
      highest percentage of poor results was observed in surgical reposition with
      internal fixation (37%). The cause of failure in the majority of patients is
      according to the authors inadequate reposition of fragments. The authors discuss
      different types of treatment. They recommend non-surgical reposition with
      percutaneous pinning, even for less dislocated extension supracondylar fractures
      of the humerus as well as for fractures complicated by vascular injuries.

PMID- 7725176
TI  - [A solitary congenital hepatic cyst].
AB  - The author discusses a congenital, solitary, multilocular liver cyst in a two
      year-old boy. The cyst originated in the margo ventralis of the right liver lobe.
      Clinically it was manifested by marked enlargement of the abdomen. The diagnosis
      was established by ultrasonography. The whole cyst was removed surgically.

PMID- 7725177
TI  - [Surgical laparoscopy in inguinal hernias, results of 143 operations].
AB  - The authors present a new surgical approach in inguinal hernias by the
      laparoscopic route, using a prolene mesh and a transabdominal preperitoneal
      approach. The advantages are excellent anatomical orientation, reduction of
      relapses, reduction of the postoperative discomfort, shorter convalescence and
      more rapid return to work. The future will show whether the described procedure
      is optimal.

PMID- 7725178
TI  - [The V-Y surgical flap vascularized by the musculoaponeurotic layer for covering
      scalp defects].
AB  - The author describes a method for covering skin defects of the scalp combining
      the principles of V-Y plasty and vascularization by means of the
      musculoaponeurotic layer. It is a simple operation, using the hairy skin in the
      vicinity of the defect with direct closure of the defect after transposition of
      the flap. With regard to the satisfactory cosmetic results, the method is
      suitable not only for primary defects after excision of tumours but also for
      medium-sized alopecias.

PMID- 7725179
TI  - [Peroperative prophylaxis with peroral Tarivid (Hoechst) in laparoscopic
      cholecystectomy].
AB  - The author gives an account on the healing of surgical wounds in a group of 111
      patients operated on account of cholelithiasis. The patients were given ofloxacin
      by the oral route during the peroperative stage as ultra-short antimicrobial
      prophylaxis. The possibility to administer the drug by the oral route in the
      peroperative period is a new finding.

PMID- 7725180
TI  - [Personal experience with laparoscopic cholecystectomy].
AB  - During the period of 29 months the first 100 laparoscopic cholecystectomies were
      performed at the Department of Surgery of the Ruzinov Hospital in Bratislava.
      There were 79 women and 21 men with mean age of 41.5 years (16-67). All
      operations were modified by the use of only 3 incisions. In 2 patients were the
      operations converted to open colecystectomy because of perforation of gallbladder
      in 1 patient because of bleeding. The average operating time was 99.1 minutes (35
      225). Intraoperative cholangiography was not carried out in any patient. 2
      patients were reoperated because of slipping of the clips from ductus cysticus
      and 1 patient because of hernia in a scar. All laparoscopic cholecystectomies
      were planned. The average hospital stay was 5.8 days (3-12). There was no death
      in our series.

PMID- 7725181
TI  - [Collagen with gentamicin in the treatment of an infected vascular prosthesis
      (case report)].

PMID- 7725182
TI  - [Serum levels of cytokines as a measure of response to stress after various types
      of elective gallbladder surgery].
AB  - The authors investigated the cytokine levels in patients after laparoscopic
      cholecystectomy (LCHE), conventional open cholecystectomy (OCHE) and complicated
      open cholecystectomy (KOMPL) in order to assess whether there is a relationship
      between cytokine levels and the general reaction of the organism, the type and
      extent of the operation. They did not find an increase of IL-1 or IL-2 levels in
      any of the patient groups. The IL-6 concentration was slightly raised only in
      three patients of the OCHE group three hours after surgery and this rise
      persisted for 24 hours. In the KOMPL group there was a more marked rise of IL-6
      in 9 patients within 3 hours after surgery, persisting in 6 patients for 24 hours
      and in 2 patients for 48 hours. The TNF values were similar; in group OCHE they
      were slightly elevated in 2 patients 24 hours after operation. In the KOMPL group
      these values were elevated in 5 patients for 3 hours after surgery and this
      increase persisted in 2 for 24 hours after surgery. Based on the investigation of
      cytokine levels, which is a recent indicator for evaluating the reaction of the
      organism to stress, conclude that laparoscopic cholecystectomy is a minimal
      stress for the patient and is associated with a zero defence reaction of the
      organism, if evaluated according to serum cytokine concentrations.

PMID- 7725183
TI  - [Distant heart procurement in the Czech and Slovak Republics].
AB  - Heart transplantation (HTx) became an established treatment of the end stage
      heart failure. The limiting factor of transplantation activity is the
      availability of donors which could be expanded by multiorgan harvesting and
      distant heart procurement (DHP). In spite of the fact that only 4-5 hours of
      could ischaemia (CI) is favourable it is still acceptable to organize the DHP
      within the radius over 1000 km from a recipient hospital. Good co-ordination, he
      best communication and transportation technology are absolutely necessary. Only
      in the case when there is no local recipient on the waiting list fr the HTx we
      offer an organ abroad. Paediatric Transplant Center Motol has been offered such
      19 heart donors since 1992. 7 of them were accepted and in 4 (donor age 10-40 y.)
      successful DHP was performed, the organs were transported (900-1100 km) and HTx
      were performed at Harefield Hospital, UK. CI was 4:20-5:05 hours (mean 4:36). Two
      organs were used for orthotopic HTx (OHTx), two for heterotopic HTx (HHTx). Two
      failed due to the acute rejection. One was successfully retransplanted, went into
      chronic renal failure and is maintained on dialysis. Another recipient died 1 w.
      after HHTx due to the failure of his own heart. One recipient has been living
      already 1 y. since his OHTx. This experience demonstrates the ability and
      competence to organize and perform the DHP by a local team even in our
      conditions. We consider it suitable and necessary prerequisite to be able to
      start our own paediatric HTx programme.

PMID- 7725185
TI  - College Medical Francais des Professeurs d'Anatomie (CMFPA) membership list.

PMID- 7725186
TI  - Anatomy between humanism and the renaissance.

PMID- 7725184
TI  - [Endoscopic therapy of an adenoma of Vater's papilla].
AB  - The authors give an account of a case-history of a patient admitted to the
      department of surgery on account of obstructive jaundice. ERCP revealed a tumour
      of the ampulla of Vater and was removed by means of an polypectomy loop. After
      operation a prompt drop of bilirubin and liver test values was recorded. After
      three months a check-up ERCP revealed at the site of the papilla patent orifices
      of the d. choledochus and d. pancreaticus without signs of a relapsing tumour. In
      benign tumours and under optimal local conditions an endoscopic procedure can be
      selected.

PMID- 7725187
TI  - Anatomic bases of the forearm compartment syndrome.
AB  - One of the most common sites for the compartment syndrome (CS) is the forearm.
      Its compartments have been studied by injection of colored gelatin into the
      particular anatomical spaces. The three "pressure-measuring-points" recommended
      in the clinical literature to measure intracompartmental tissue pressure in
      equivocal diagnostic cases were used for the dye injections on the forearms of
      five preserved cadavers of adults. However, instead of the compartments
      especially affected in CS two adjacent spaces were revealed. In order to
      elucidate the clinical relevant spaces two additional approaches for the
      injection had been used. Cross-sections at 15 mm intervals of the injected
      forearms had been performed. Some of them are presented and schematically
      summarized in this article. Recent studies have suggested that there are
      different guidelines for description of the anatomically isolated spaces.
      However, especially one of these spaces seems to be responsible for the CS on the
      forearm. The remarkable features of this so called "deep flexor compartment" are
      its very restrictive envelopes, its rare fascial contacts, its impermeable seal
      in proximal-radial direction as well as the extremely endangered structures
      within the compartment. The flexor carpi ulnaris muscle is recommended to be the
      "primary structure" for measuring the tissue pressure as well as for surgical
      decompression. The article reviews the anatomical base of the CS.

PMID- 7725188
TI  - Anatomic basis of venous drainage in donor flaps.
AB  - The venous architecture in donor flaps was observed in 17 fresh cadavers by
      injection of latex or ink into the vessels or by making corrosion-cast specimens.
      The pattern of the veins resembles that of the arteries, with the difference that
      there is another set of venous trunks which do not accompany the arteries.
      Because these trunks are of larger caliber, they are the main drainage route for
      flaps. There are three types of drainage based on the anatomical architecture: 1)
      the superficial trunk is the main drainage path; 2) the deep trunk is the main
      path; 3) both superficial and deep veins are involved. These morphological
      considerations are the basis for selection of veins for anastomosis in
      microsurgery. The axial veins in temporal, frontal and facial flaps on the dorsum
      of the hand and the foot usually loosely accompany the axial arteries. The
      characteristics of these vascular pedicules should be studied in transplant
      operation.

PMID- 7725189
TI  - Anatomical basis for the separation of four cardiac zones in the walls of human
      heart ventricles.
AB  - The coronary vessels of 70 human hearts were visualized postmortem by injection
      of the coronary arteries with a X-ray opaque substance (for angiographic studies)
      or with a low viscosity resin (to obtain vascular casts). Analysis of the data
      suggests a new anatomical systematization of the vascularization of the
      myocardial tissue of human heart ventricles: it can be divided into four zones
      each having a different origin of the arterial vessels. These four components of
      the heart ventricles are the antero-septal (AS), postero-septal (PS), left
      lateral (LL), and right-lateral (RL) zones. They correspond to the territories of
      the anterior interventricular branch of the left coronary artery (AS zone), of
      the posterior interventricular branch of the right coronary artery (PS zone), of
      the left circumflex artery (LL zone), and of the right coronary artery (RL zone)
      up to the origin of the posterior interventricular artery. This systematization
      of the arterial heart ventricles in zones offers a balanced division of the
      myocardial tissue, since each of the four zones occupied about one fourth of the
      total volume of the ventricles. In our samples, the most common distribution of
      segments in the wall of heart ventricles was the following: 16 segments in the AS
      zone, 11 segments in the PS zone, 5 segments in the LL zone, and 4 segments in
      the RL zone. The separation of four zones in the walls of heart ventricles, each
      of them made up of different segments, may be helpful in the understanding of the
      pathophysiology of myocardial ischemia, and also in the choice of surgical
      strategies to treat aneurisms of the heart ventricle wall.

PMID- 7725190
TI  - Morphological variants of the suprapatellar septum. An anatomical study in
      neonatal cadavers.
AB  - In order to study the incidence and variations of the suprapatellar septum, 100
      knee joints of 50 neonatal cadavers were examined anatomically. In 26% of the
      neonatal knee joints, a complete septum was found. Perforated septa with
      different shapes and residual septa were seen in 64% knees. A complete involution
      of the former septum was found in 10 of our cases. A suprapatellar septum
      combined with a mediopatellar plica was found in 18 knees.

PMID- 7725191
TI  - Longus colli has a postural function on cervical curvature.
AB  - To determine the postural role of longus colli (LC) and dorsal neck muscles, we
      have studied the relationship between their cross-sectional areas related to
      their force of contraction and the lordosis and the length of the cervical spine.
      This study was carried out in 36 healthy subjects. Muscle cross-sectional areas
      were measured by computerized tomography. The index of lordosis and the length of
      the cervical spine were measured on an X-ray profile. The cross-sectional area of
      LC was correlated to the lordosis index (R = -0.432, p < 0.02) whereas all the
      other parameters were not correlated. The authors conclude that LC counteracts
      the lordosis increment related to the weight of the head and to the contraction
      of the dorsal neck muscles. Postural functions of LC and postcervical muscles are
      complementary. They form a sleeve which encloses and stabilizes the cervical
      spine in all positions of the head.

PMID- 7725192
TI  - Vascular networks of the nucleus lentiformis.
AB  - The nucleus lentiformis vascular networks were studied in 30 brains by injecting
      the vascular system with gelatinous Indian ink. The nucleus lentiformis is
      divided into a medial part, the globus pallidus, and a lateral part, the putamen.
      These two parts differ completely from one another in their embryology, structure
      and functions. For these reasons, each part presents a specific vascular network.
      The putaminal network is dense and shows many similarities with the cerebral
      cortex vascular network; the pallidal one is simpler and less dense. These two
      vascular networks are located close to each other without overlapping. Their
      specificity may be in relation with the histological structure, with the
      morphogenetic evolution or with the functional activity of both nuclei to which
      they provide the vascularization.

PMID- 7725194
TI  - Preliminary opto-electronic study on vertebral movement.
AB  - Opto-electronic systems utilising measurement of displacement of skin markers
      allows study of movement in the living subject. The authors have used this method
      in a kinematic study of the thoracic and lumbar spine measuring the displacement
      of skin markers placed over the spinous processes. It was possible to approach
      the physiological state of these complex movements once the apparatus had been
      calibrated to the correct level, and the error margins minimised. Repeated
      measurements confirmed the reliability of this method even if movement of the
      skin with respect to the bony reference points introduced some margin of error.
      Three dimensional displacement of the vertebrae were measured during voluntary
      movements of the spine demonstrating the complex geometry. Since opto-electronics
      are non-invasive they constitute an important advance in the study of the
      kinematics of the spine.

PMID- 7725193
TI  - On the presence of a secondary cartilage in the mental symphyseal region of human
      embryos and fetuses.
AB  - The presence of a secondary cartilage in the mental symphyseal region was
      examined in this study. A double-staining method with alcian blue and alizarin
      red S was performed on both whole human embryos and fetuses (developmental age
      between 8 and 17 weeks, crown-rump length, CRL, between 37 and 124 mm) and their
      disjointed mandibles. Histological and histochemical techniques were applied to
      transverse serial sections of whole disjointed fetal heads. The ossification
      process observed in the mental symphysis is quite different from that of the
      mandibular body, whose membranous ossification is induced by the contiguous
      Meckel's cartilage. No evidence of any fusion of Meckel's cartilage with the
      symphyseal cartilage, that lies within the symphyseal space, was detected. On the
      basis of these findings, we suggested that the mental secondary cartilage is able
      to change into bone according to an endochondral ossification process. Moreover,
      the role of mechanical causes in the development of the mental symphysis was
      hypothesized.

PMID- 7725195
TI  - Preliminary findings on the effect of load-carrying to the structural integrity
      of the cervical spine.
AB  - Carrying loads on the head is a common practice in rural Zimbabwe. Headloading
      imposes a considerable amount of strain to the axial skeleton. The cervical
      spine, being the most cranial and mobile part of the vertebral column, may be
      susceptible to spondylosis or disc degeneration in headloading. Age as well as
      the effects of intrinsic factors on cervical spondylosis have been well
      documented. However, studies on the effect of extrinsic weight bearing to
      spondylosis on the cervical spine are lacking. In this study, the effect of
      headloading on the pattern of spondylosis attributed to aging was examined.
      Results indicated that age led to significant degeneration of the fifth
      intervertebral disc space (P < 0.05) as well as significant straightening of the
      lordotic curve (P < 0.01). Load carrying seems to accentuate the straightening of
      the curve (P < 0.001). The results also suggest that headloading creates a shift
      in the degeneration from the fifth intervertebral disc space to higher levels. It
      is concluded that carrying heavy loads on the head alters the pattern of
      degenerative changes of the cervical spine.

PMID- 7725197
TI  - A study of the nutrient foramina of lower limb long bones.
AB  - In this study a total of 269 adult lower limb long bones were examined to
      determine the number and location of the nutrient foramina in the shafts of
      bones. The mean of foraminal index was 48.82 for femur, 33.17 for tibia, and
      47.82 for fibula. The number of foramina noted were: two on the linea aspera in
      the middle third of the femur, one on the posterior surface of the upper third of
      the tibia, and one on the posterior surface of the middle third of the fibula.

PMID- 7725196
TI  - Direct lymphatic drainage from the esophagus into the thoracic duct.
AB  - The lymphatic vessels from around the esophagus which drain into the thoracic
      duct were identified macroscopically and histologically in 106 cadavers. Direct
      lymphatic drainage to the duct was macroscopically demonstrated by 84 vessels in
      46 cases (43.4%). In 23 cases (19.8%), large collecting vessels arose from the
      thoracic esophagus and opened directly into the duct. In most of these cases
      (15/23) these lymphatic connections were found at the levels of the 1st-3rd or
      6th-8th thoracic vertebrae. Histologic study revealed that two vessels originated
      from the fine lymphatic plexus in the esophageal adventita, which showed
      monocytic infiltration. In 11 of the 23 cases, an intercalated node was found
      along the thoracic duct. The results suggest that lymph drains rapidly into the
      systemic circulation via the thoracic duct. In view of the clinical applications
      in esophageal carcinoma, previous accounts of the extramural esophageal
      lymphatics concerned in direct drainage are discussed.

PMID- 7725199
TI  - A computerised technique for morphometry and 3D reconstruction of embryological
      structures.
AB  - In the last decade we have witnessed the development of software technology
      capable of image analysis and morphometry [1, 8-12]. Although these methods are
      sometimes difficult to master in a practical sense, they are tremendously
      efficient and precise when applied to the study and measurement of developing
      biological structures, particularly in the field of embryology. In this study we
      describe the application on human embryos of an image analyzing system that
      enables one to perform quantitative analyses of the morphology and size of
      developing organs and structures as well as their ultimate three-dimensional
      reconstruction (3DR).

PMID- 7725198
TI  - Radioanatomic study of the gastrocolic venous trunk.
AB  - The mode of formation, measurements and frequency of occurrence of the
      gastrocolic venous trunk were studied by the injection-corrosion technique in a
      series of 54 anatomic specimens and by the analysis of 50 CT studies in patients
      without hepatic or pancreatic disease. The gastrocolic trunk was found in 51 of
      the 54 anatomic specimens and in 27 of the 50 CT studies. The great variability
      in its formation, whether bipodal, tripodal or quadripodal, was noted. With a
      mean diameter of 4.9 mm, it opened into the anterior, right or antero-left
      aspects of the superior mesenteric v. at a mean distance of 15 mm below the
      inferior border of the spleno-mesenteric confluence. The value of preliminary CT
      assessment before an operation for portal hypertension or a pancreatic tumor or
      in the diagnosis of a splenic thrombosis is emphasised.

PMID- 7725200
TI  - Imaging of the facial canal by means of multiplanar angulated 2-D-high-resolution
      CT-reconstruction.
AB  - The facial canal containing the intratemporal portion of the facial nerve is very
      important for the otologist and radiologist concerning fractures and other
      lesions of the temporal bone. Axial and/or coronal standards are sufficient for
      imaging of the labyrinthine and the mastoidal segment of the facial canal. The
      sensitivity of visualization (sensitivity = number of identified structures per
      number of examinations) of the tympanic segment, however, is low and particularly
      the pyramidal segment (elbow, posterior knee) is not visualized in these
      standards. Based on anatomical considerations a new plain for imaging both the
      tympanic and mastoidal segment in continuity was obtained. The pyramido
      longitudinal plain is achieved by a twice angulated 2-D-reconstruction based on
      axial high-resolution CT-scans.

PMID- 7725201
TI  - The morphology of articular cartilage assessed by magnetic resonance imaging
      (MRI). Reproducibility and anatomical correlation.
AB  - Quantitative assessment of cartilage volume and thickness in a formalin-alcohol
      fixed specimen of a human patella was conducted with magnetic resonance imaging
      (MRI), as it is still unclear whether the morphology of normal and damaged
      cartilage can be accurately demonstrated with this technique. MR imaging was
      carried out at 1.0 T (section thickness 2 mm, in-plane-resolution 0.39-0.58 mm)
      with the following pulse sequences: 1) T1-weighted spin-echo, 2) 3D-MPRAGE, 3) 3D
      FISP, 4) 3D-MTC-FISP, 5) 3D-DESS, 6) 3D-FLASH. Following imaging, the patella was
      sectioned perpendicular to the articular surface at intervals of 2 mm with a
      diamond band-saw. The volume of its cartilage was determined from the anatomical
      sections and the MR images, using a Vidas IPS 10 image analysing system
      (Kontron). Measurements were carried out with and without the low-signal layer in
      the transitional zone between the articular cartilage and the subchondral bone.
      If the low-signal layer was included, the volume was overestimated with MRI by 16
      to 19%. Without the low-signal layer the volumes were less than those determined
      from the anatomical sections: T1-SE-18.2%, MPRAGE -22.6%, FISP -17.1%, MTC-FISP 
      9.5%, DESS -9.3% and FLASH -6.1%. The coefficient of variation for a 6-fold
      determination of the volume amounted to between 6.2% (T1-SE) and 2.6% (FLASH).
      The FLASH sequence allowed the most valid and reproducible assessment of the
      cartilage morphology. The remaining difference from the real volume of the
      cartilage may be due to the fact that the calcified zone of the cartilage is not
      delineated by MRI.

PMID- 7725202
TI  - Submandibular gland with multiple ducts.
AB  - A morphological peculiarity was observed in the form of a submandibular gland
      having three ducts. These ducts opened separately into the oral cavity. Only the
      upper and the largest of these three ducts was in the usual position and had the
      expected relation to the lingual nerve. Such a condition is to be kept in mind by
      a surgeon or a radiologist performing sialography. Unless each of the duct in
      instilled he may miss pathological findings.

PMID- 7725203
TI  - Vagocervical complex replacing an absent ansa cervicalis.
AB  - Absence of the ansa cervicalis was noticed in only one out of 200 cadavers, and
      that only on the right side, where it was replaced by the vagocervical complex.
      This complex was formed by the vagus nerve with the C1 and C2 components from the
      cervical plexus, giving off a descending branch to supply the infrahyoid muscles
      of the neck.

PMID- 7725204
TI  - In memoriam Miltiades Papamiltiades (1910-1987): eminent Greek anatomist and
      ambassador of Franco-Hellenic friendship.

PMID- 7725205
TI  - Minimal access surgery and the "golden period" for conversion.

PMID- 7725206
TI  - Laparoscopic hernia repair. Three-year experience.
AB  - The basis of laparoscopic transabdominal preperitoneal repair (LTPR) of herniae
      rests upon the utilization of a prosthetic screen to cover hernia defects.
      Preperitoneal prosthetic screen interposition reproduces the effect of the
      inguinal shutter mechanism. In this 3-year longitudinal study, one surgeon
      performed 224 laparoscopic hernia repairs (LTPR) on 164 patients. These patients
      have been examined postoperatively by that surgeon and a trained research
      assistant according to an established protocol. Patient mean age was 50.6 years;
      45 cases involved bilateral inguinal herniae (21.5%); 20 laparoscopic repairs
      were for failed open repair (9.6%); and 46 herniae were incarcerated (22%) at the
      time of laparoscopic repairs. There were no intraoperative complications. Two
      procedures required conversion to open repair, the first because of uncertainty
      regarding incarcerated bowel viability and the second for massive abdominal-wall
      adhesions. Two laparoscopic repairs recurred and required subsequent repair.

PMID- 7725207
TI  - Incidence of complications following laparoscopic hernioplasty.
AB  - Smaller individual series on the outcome of laparoscopic hernioplasty techniques
      have been reported. This study reports on the complications of 3,229 laparoscopic
      hernia repairs performed by the authors in 2,559 patients. The TAPP
      (transabdominal preperitoneal) technique was the most frequently performed: 1,944
      (60%). The totally preperitoneal technique was performed 578 (18%) times. The
      IPOM (intraperitoneal onlay mesh) repair was performed 345 (11%) times. The plug
      and-patch technique was used 286 (9%) times and simple closure of the hernia
      defect without mesh was used in 76 (2%) repairs. Overall, there were 336 (10%)
      complications: 17 (0.5%) major and 265 (8%) minor. There were 54 (1.6%)
      recurrences, with a mean follow-up of 22 months. The TAPP technique had 19 (1%)
      recurrences and 141 (7%) complications. There were four bowel obstructions in
      this subgroup from herniation of small bowel through the peritoneal closure and
      trocar sites. The totally preperitoneal technique had no recurrence and 60 (10%)
      complications. The IPOM group had 7 (2%) recurrences and 47 (14%) complications.
      The plug-and-patch technique had 26 (9%) recurrences and 24 (8%) complications.
      The simple closure of the internal ring had 2 (3%) recurrences and 10 (13%)
      complications. Laparoscopic hernioplasty is not without complications.
      Laparoscopic hernioplasty is not without complications. Training, experience, and
      attention to technique will prevent some of these complications.

PMID- 7725208
TI  - Documentation of abdominal exploration during laparoscopic cholecystectomy.
AB  - To assess the documentation of intraperitoneal exploration and events during
      laparoscopic cholecystectomy, we reviewed 200 dictated operative reports from
      eight different institutions. The 200 laparoscopic cholecystectomies were
      performed by 40 different surgeons on 158 female patients and 42 male patients. A
      description of the gallbladder was included in 134 (67%) reports and not
      mentioned in 66 (33%) reports. Fifty-four (27%) reports did not mention any
      intraperitoneal findings away from the gallbladder. Another 36 (18%) of the
      reports contained only a general comment indicating that no abnormalities were
      seen in the abdomen (excluding the gallbladder). The other 110 (55%) reports
      mentioned at least one specific site or finding in the abdomen other than the
      gallbladder. The most commonly mentioned sites were the liver, bowel, and
      stomach. Only 42 (21%) operative notes described what happened to the gallbladder
      contents: 30 described spillage of bile and/or gallstones and 12 stated that no
      spillage occurred. CONCLUSIONS: Laparoscopic cholecystectomy operative notes have
      often lacked a description of gallbladder appearance, documentation of abdominal
      exploration, and/or documentation of complete removal of the gallbladder and its
      contents.

PMID- 7725209
TI  - Laparoscopic cholecystectomy. Cause of conversions in 1,300 patients and analysis
      of risk factors.
AB  - In 1,300 patients undergoing laparoscopic cholecystectomy (LC) 56 patients (4.3%)
      required conversion to open cholecystectomy (OC); 41 (73%) of the conversions
      were elective, whereas 15 (27%) were enforced. The causes of the 56 conversions
      are described and analyzed. Logistic regression analysis of 23 parameters
      identified the following data as associated with a higher risk for conversion:
      pain or rigidity in the right upper abdomen (P < 0.01), thickening of the
      gallbladder wall on preoperative ultrasound (P < 0.05), intraoperatively found
      dense adhesions to the gallbladder or in Calot's triangle (P < 0.001), and
      intraoperatively found acute inflammation of the gallbladder (P < 0.01). Clinical
      findings of an acute cholecystitis associated with intraoperative dense scarring
      in Calot's triangle were the best factors predicting conversion from LC to OC. As
      a result of the study we preoperatively select our patients for either LC or OC,
      and a difficult case is performed by a more experienced surgeon to keep
      conversion rate and complications low.

PMID- 7725211
TI  - Symptomatic gallbladder stones. Cost-effectiveness of treatment with
      extracorporeal shock-wave lithotripsy, conventional and laparoscopic
      cholecystectomy.
AB  - In order to strike the most favorable balance between health benefits and costs,
      three treatment modalities for symptomatic cholelithiasis were compared in a cost
      effectiveness study: extracorporeal shock-wave lithotripsy (ESWL), conventional
      cholecystectomy (CC), and laparoscopic cholecystectomy (LC). Data were analyzed
      from 55 patients who were treated by ESWL, 45 patients who had CC, and 47
      patients who had LC. The study was performed by analysis of patients charts and a
      written questionnaire. After ESWL 35% of the patients were free of stones, 23%
      had fragments < or = 5 mm, and 42% had fragments > 5 mm at 1-year follow-up.
      Persistent complaints were reported by 59% after ESWL, 11% after CC, and 14%
      after LC (P < 0.001). New complaints arose in 12% after ESWL, 11% after CC, and
      in 5% after LC (P = NS). Patient appreciation score was highest for LC and lowest
      for ESWL. Mean hospital stay was 2.4 days for ESWL, 10 days for CC, and 3.5 days
      for LC. Overall costs of treatment were: $5,066 for ESWL; $5,893 for CC; and
      $3,117 for LC. This study reveals that laparoscopic cholecystectomy is the most
      effective treatment of the large majority of patients with symptomatic
      cholelithiasis. ESWL should only be considered in the case of a solitary,
      relatively small, completely radiolucent stone.

PMID- 7725210
TI  - Complications after laparoscopic cholecystectomy. Coordinated radiologic,
      endoscopic, and surgical treatment.
AB  - The diagnostic and therapeutic approaches used for patients referred for bile
      duct injuries and other major complications after laparoscopic cholecystectomy
      (LC) were reviewed and the results of a coordinated radiologic, endoscopic, and
      surgical approach were assessed. From April 1991 to October 1993, 23 patients
      were observed. Seven patients had biliary strictures, five had biliary lesions,
      five presented with retained common bile duct (CBD) stones, and one had a minor
      cystic duct leak. Five patients had miscellaneous abdominal fluid collections; in
      addition, biloma or bile ascites were present in 10/23 cases. Correct definition
      of iatrogenic lesions was mainly made by endoscopic retrograde cholangiography
      (ERCP) (n = 15), associated in six cases also with percutaneous cholangiography
      (PTC). "Minimally invasive" treatment included the full range of endoscopic and
      interventional radiological procedures. Six patients with biliary strictures, one
      patient with a biliary lesion, all five patients with residual CBD stones, and
      four patients with abdominal collections were treated by "minimally invasive"
      techniques: Therefore, laparotomy was avoided in 70% of cases (16/23 patients).
      Open surgery was necessary in 7/23 patients (30%), because of ductal lesion (n =
      4), ductal stricture by endoloop (n = 1), iliac artery injury (n = 1), and
      phlegmon of gallbladder bed (n = 1). It appears that careful assessment of
      complications after LC is mandatory and often requires the combined use of
      ERCP/PTC and cross-sectional imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725212
TI  - Evaluation of the shock-wave pattern for endoscopic electrohydraulic lithotripsy.
AB  - We evaluated the electrical events and the resulting shock waves of the spark
      discharge for electrohydraulic lithotripsy at the tip of a 3.3F probe. Spark
      generation was achieved by variable combinations of voltage and capacity. The
      effective electrical output was determined by means of a high-voltage probe, a
      current coil, and a digital oscilloscope. Peak pressures, rise times, and pulse
      width of the pressure profiles were recorded using a polyvinylidene difluoride
      needle hydrophone in 0.9% NaCl solution at a distance of 10 mm. The peak pressure
      and the slope of the shock front depend solely on the voltage, while the pulse
      width was correlated with the capacity. Pulses of less than 1-microsecond
      duration can be obtained when low capacity is applied and the inductivity of the
      cables and plugs is kept at a low level. Using chalk as a stone model it was
      proven that short pulses of high peak pressure provided by a low capacity and a
      high voltage have a greater impact on fragmentation than the corresponding
      broader shock waves of lower peak pressure carrying the same energy.

PMID- 7725213
TI  - Survey on Torino courses. The impact of a two-day practical course on
      apprenticeship and diffusion of laparoscopic cholecystectomy in Italy.
AB  - Since March 1991 a monthly course on laparoscopic cholecystectomy has been
      organized at the Department of Surgery of the University of Turin. To evaluate
      the impact of this course and to obtain feedback from surgeons in order to
      improve the teaching of laparoscopic surgery, detailed questionnaires were sent
      to the participants of the first 20 courses. The outcome of this survey shows
      that short-residency "hands on" courses do not represent a completely
      satisfactory training, either for practicing surgeons or for residents, mainly
      because of the constraints of time and the lack of proctoring and supervision.
      Besides, the present study shows a significant difference in the diffusion of
      laparoscopic surgery in different areas of Italy. However, clinical results
      reported by this group of surgeons are satisfactory and comparable to the best
      multicentric series: 2,127 laparoscopic cholecystectomies were performed by 48
      surgeons with a conversion rate of 6% and a complication rate of 2.4%.

PMID- 7725214
TI  - Tumor growth after laparotomy or laparoscopy. A preliminary study.
AB  - We investigated the effects of laparotomy and insufflation on tumor establishment
      and growth in a murine model. Twenty female mice received intradermal inoculation
      of a low dose of tumor cells (2 x 10(3)) derived from the MC2 mouse mammary
      carcinoma cell line. Ten of these mice underwent laparotomy and ten received
      intraperitoneal insufflation with carbon dioxide gas at a pressure of 5 mmHg for
      30 min. Tumor growth was followed postoperatively. By postoperative day 14,
      tumors had grown in zero of the ten insufflated mice and in seven of the ten
      laparotomy-group mice (P < 0.005). By postoperative day 30, tumors had grown in
      one of the ten insufflated mice and in eight of the ten laparotomy-group mice (P
      < 0.007). Ten additional mice received a high-dose inoculum of cells (1 x 10(6))
      followed by either laparotomy or intraperitoneal insufflation. Upon sacrifice 12
      days later, all mice had developed tumors, but the laparotomy group's tumors were
      almost three times as large, by mass, as tumors in the insufflated group (70.5 +/
      23.5 mg vs 25.8 +/- 9.5 mg; P < 0.02). These results suggest that laparotomy
      confers a permissive effect on tumor establishment and growth in a murine model
      not seen after peritoneal insufflation. We hypothesize that this may be a
      function of relative immunosuppression following laparotomy which is not present
      following peritoneal insufflation. These data may be important when choosing a
      route of access to the peritoneal cavity for cancer resection.

PMID- 7725215
TI  - The use of pancreatic ductoscopy in the operative management of benign and
      malignant pancreatic disorders.
AB  - Direct visualization of the pancreatic duct was helpful in decision making during
      complex pancreaticobiliary operations. Two-, 3-, or 5-mm scopes were introduced
      into the pancreatic ducts of 32 patients with pancreatic disorders. Scopes were
      passed into the ductal system of: (1) 16 patients undergoing
      pancreaticojejunostomy; (2) six patients undergoing pancreaticoduodenectomy; (3)
      four patients with pancreatic pseudocysts or choledochal cysts: (4) two patients
      undergoing resection of the pancreatic tail; and (5) two patients undergoing
      accessory ductoplasty for pancreas divism or stricture. Eight patients had
      calculi removed utilizing the scope, and multiple strictures were identified and
      filleted. Pancreatic ductoscopy was used in two patients to document successful
      sphincteroplasty of an accessory duct. In two instances benign pancreatic duct
      tumors were removed. Pancreatic ductoscopy was used to search for coexistent duct
      neoplasms in the eight patients who underwent resection. The technique permits
      intraoperative inspection, biopsy, and removal of lesions intrinsic to the ductal
      system. Combined with surgical procedures this endoscopic method proved a useful
      adjunct in difficult cases.

PMID- 7725216
TI  - Transanal endoscopic microsurgery. Results of the initial ten cases.
AB  - Transanal endoscopic microsurgery (TEM) permits precise excision of favorable
      tumors from the mid and proximal rectum, thus avoiding transsacral and low
      anterior resection in select cases. Ten patients underwent TEM resection of
      rectal tumors by a single surgeon between April 1992 and August 1993. All
      patients first underwent endorectal ultrasound. Villous adenomas ranging from 3.2
      to 4.5 cm in size (mean, 3.9 cm) in eight patients and T1 adenocarcinomas of 1.5
      and 2.5 cm (mean, 2 cm) in two patients were excised. Resection was performed
      using the mucosectomy method in three and by full-thickness excision in seven
      patients. Distal extent of tumors ranged from 6 to 11 cm from the anal verge. The
      operative time in these initial ten cases ranged from 75 to 220 min (mean, 138
      min). Estimated blood loss ranged from 0 to 550 cc (mean, 85 cc). Complications
      occurred in two patients (pseudomembranous colitis; fever of unknown origin). The
      mean length of hospital stay was 2.7 days. To date, one tumor has recurred,
      requiring an abdominoperineal resection. In no case was conversion to
      conventional method of resection necessary at the time of TEM resection. TEM is a
      safe and effective method for resecting favorable tumors in select cases.

PMID- 7725217
TI  - Endoscopic retrograde cholangiographic demonstration of a double gallbladder
      following laparoscopic cholecystectomy.

PMID- 7725218
TI  - Experience with laparoscopic double gallbladder removal.
AB  - Double gallbladder is a rare congenital anomaly and an encounter with it while
      performing cholecystectomy laparoscopically is a challenge to the laparoscopic
      surgeon. A 28-year-old man complaining of epigastric pain was evaluated at Teikyo
      University Hospital, Mizonokuchi, Japan. There were no abnormal laboratory
      findings. Ultrasonography revealed an acoustic shadow in each compartment without
      any inflammatory changes in the gallbladder. No lesions were endoscopically noted
      in the stomach. CT scan could not demonstrate the anomaly. ERCP revealed a
      duplication of the gallbladder shadow with a stone in each vesicle and also the
      confluence of two cystic ducts from both the gallbladders draining into the
      common bile duct (CBD). Laparoscopic cholecystectomy was performed successfully
      in this case. This paper presents this particular case because of double
      gallbladder's rarity in the literature and to emphasize the importance of
      preoperative cholangiographic evaluation for double gallbladder. The laparoscopic
      surgeon is given an idea of the meticulous dissection at the "hepatocystic
      triangle" due to the various other vascular and other congenital anomalies
      associated with it. An account of the classification of this congenital
      abnormality and its various types is also discussed here.

PMID- 7725219
TI  - Incomplete excision of the gallbladder during laparoscopic cholecystectomy.
AB  - Dissection and transection of the cystic duct close to the gallbladder has been
      advocated as a means of avoiding common bile injury during laparoscopic
      cholecystectomy (LC). We present three cases in which inadequate identification
      of the gallbladder-cystic duct junction resulted in incomplete cholecystectomy.
      In two patients an unsecured gallbladder infundibulum presented as cystic duct
      leaks and one patient developed recurrent symptomatic cholelithiasis. These cases
      emphasize the need for complete dissection and visualization of the cystic duct
      at the gallbladder prior its division and secure ligation during LC.

PMID- 7725220
TI  - Conservative laparoscopic treatment of a posttraumatic splenic cyst.
AB  - Laparoscopy has recently been demonstrated to be a useful alternative to open
      surgery for the surgical treatment of spleen disorders, and it can also
      facilitate a conservative approach for treatment of selected spleen lesions. We
      present the laparoscopic spleen-preserving treatment of a post-traumatic spleen
      cyst. A 28-year-old female presented a mass in the left hypochondrium immediately
      after an uneventful pregnancy. CT revealed a splenic cyst of 10 x 8 cm.
      Laparoscopic exploration showed a cyst located in the lower pole of the spleen.
      All the cyst wall not covered by spleen tissue (70%) was excised, and the
      fragment of cyst wall was recovered through a bag. The patient recovered
      uneventfully and was discharged 72 hours later. The laparoscopic approach should
      be considered for evaluation and treatment of selected benign cystic lesions of
      liver, retroperitoneum or spleen origin.

PMID- 7725221
TI  - Meralgia paraesthetica following laparoscopic inguinal hernia repair. An
      anatomical analysis.
AB  - Entrapment of the lateral cutaneous nerve of the thigh (LCNT) is a recognized
      complication of laparoscopic hernia repair. In our first 10 patients in a series
      of 30 laparoscopic herniorrhaphies we encountered two cases of meralgia
      paraesthetica, leading us to review our surgical technique and analyze the local
      anatomy in 20 LCNT cadaver dissections. The distances of the LCNT from fixed
      anatomical points were analyzed and safe margins of mesh placement at
      laparoscopic herniorrhaphy were defined.

PMID- 7725222
TI  - Endoscopy under operating microscope. A new device.
AB  - Existing technical conditions make it difficult for a single surgeon to
      simultaneously observe the endoscope and the observation field of the operating
      microscope. Video endoscopy is not adapted, because it respects neither the
      constraints of microsurgery (the surgeon has to stop observing the binoculars of
      the microscope to watch the video screen) nor the micromanipulations necessary
      for the specialties using micro endoscopy. A new device is described that closely
      joins endoscope and microscope. This coupling device allows the surgeon to
      permanently control and alternate the images according to his choice. The surgeon
      is able to observe in the binoculars the images transmitted by the endoscope
      and/or the operating microscope. This device respects the requirements of the
      microscope and, thanks to its optical capabilities, the endoscopic image is
      improved. The professions requiring double observation will improve their ability
      in diagnosis and therapy.

PMID- 7725223
TI  - Different techniques of laparoscopic end-to-end small-bowel anastomoses.
AB  - The aim of the study was to prove that laparoscopic stapling devices can be used
      to create a bowel anastomosis. Three groups with n = 6 pigs each were subjected
      to different techniques of small-bowel anastomoses. In groups I and II
      anastomosing of the bowel ends was carried out with singly placed staples using a
      hernia stapler. (Group I: Two-thirds of the circumference became inverted and one
      third everted. Group II circumferentially everted). In group III triangular
      everted anastomoses were produced using a linear noncutting stapler. All animals
      survived the observation period of 14 days and were postmortally examined.
      Average construction time was 59 min for groups I and III and 47 min for group
      II. Average diameters were 14 mm, 16 mm, and 18 mm for groups I, II, and III,
      respectively. There were no significant differences between the techniques
      concerning the stability of the anastomoses as expressed by bursting pressures.
      There were two stenoses in group I animals caused by electrocautery during
      preparation of the bowel ends prior to anastomosing. Anastomotic insufficiencies
      or fistulas were not observed clinically or with Gastrografin studies. We
      conclude that anastomoses in the pig can laparoscopically be constructed by
      employing singly placed staples as well as a linear stapler. Further
      investigations of these techniques on large bowel and human specimens are
      required prior to their clinical use in humans.

PMID- 7725224
TI  - Laparoscopic cholecystectomy with an ultrasound surgical aspirator.
AB  - Laparoscopic cholecystectomy using an ultrasound surgical aspirator has been
      performed in our department since March 1991. The horn cover was altered in order
      to be inserted through a trocar 10 mm in diameter. The main purpose of this
      device is to explore Calot's triangle by fragmentation and aspiration of the
      fatty tissue without damaging the nerves, vessels, and cystic duct. First the
      serosa of the Calot's triangle is cut via electrocautery with the sharp-angle
      hook dissector we designed. Then the cystic duct and cystic artery are
      efficiently exposed by the ultrasound surgical aspirator. This procedure is
      perfectly adapted for laparoscopic cholecystectomy. We obtained favorable results
      with the ultrasound surgical aspirator in 135 cases including 40 cases with a
      negative gallbladder, as evaluated by endoscopic retrograde cholangiography. In
      conclusion, the ultrasound surgical aspirator is suitable for skeletonizing the
      cystic duct and cystic artery, and the procedure is perfectly safe.

PMID- 7725225
TI  - Abdominal adhesions and laparoscopic hernia repair.

PMID- 7725226
TI  - Flexible sigmoidoscopy in the detection of asymptomatic neoplasia.

PMID- 7725227
TI  - Vogt-Koyanagi-Harada syndrome.
AB  - The Vogt-Koyanagi-Harada syndrome (VKH) is a bilateral, diffuse granulomatous
      uveitis associated with poliosis, vitiligo, alopecia, and central nervous system
      and auditory signs. These manifestations are variable and race dependent. This
      inflammatory syndrome is probably the result of an autoimmune mechanism,
      influenced by genetic factors, and appears to be directed against melanocytes. On
      histopathologic examination typical cases show nonnecrotizing diffuse
      granulomatous panuveitis with initial sparing and late involvement of the
      choriocapillaris and formation of Dalen-Fuchs' nodules. Fluorescein angiography,
      lumbar puncture, and echography are useful adjuncts in the diagnosis and
      management of VKH syndrome. Patients with this syndrome are treated generally
      with high dose systemic corticosteroids or, when necessary, with cyclosporine or
      cytotoxic agents. The prognosis of patients with VKH syndrome is fair, with
      nearly 60% of patients retaining vision of 20/30 or better. The complications of
      VKH syndrome that lead to visual loss include cataracts in about 25% of patients,
      glaucoma in 33%, and subretinal neovascular membranes (SRNVMs) in about 10%; the
      latter, however, are an important cause of late visual loss. These complications
      usually require medical and/or surgical intervention, including photocoagulation.
      The major risk factor for the development of cataracts, SRNVMs, and, to some
      extent, glaucoma, is chronic recurrent intraocular inflammation that may be
      resistant to corticosteroid therapy. It appears that initial treatment with high
      dose corticosteroids, combined with prolonged corticosteroid therapy at
      appropriate dosage, may minimize these complications and may improve visual
      prognosis.

PMID- 7725228
TI  - Intraepithelial sebaceous neoplasia without underlying invasive carcinoma.
AB  - Two patients with intraepithelial sebaceous neoplasia of the conjunctiva and
      cornea without an underlying invasive carcinoma are described. This
      intraepithelial disease displays the same cytologic features found in the
      conjunctival epithelium of patients with an invasive sebaceous carcinoma. The
      natural history of this incipient carcinoma is unknown. Anecdotal evidence
      indicates that some lesions can remain in situ for prolonged periods without
      undergoing transformation to an invasive carcinoma. The diagnosis of
      intraepithelial sebaceous neoplasia of the ocular surface is established by
      excluding an occult invasive carcinoma with appropriate biopsies.

PMID- 7725229
TI  - von Hippel-Lindau disease manifesting as a chiasmal syndrome.
AB  - A 21-year-old woman presented with a two year history of progressive loss of
      vision in the left eye. Brain MRI revealed a supresellar mass felt to be most
      consistent with a meningioma. However, pathologic examination including special
      stains disclosed features characteristic of hemangioblastoma. Further evaluation
      established the diagnosis of von Hippel-Lindau disease by demonstrating retinal
      capillary hemangiomas, small renal and hepatic cysts, and cervico-medullary
      masses later confirmed to be hemangioblastomas. To date, no other family members
      have displayed features of this inherited syndrome.

PMID- 7725230
TI  - Disk edema in an overweight woman.
AB  - A 46-year-old extremely obese black woman presented with headaches, blurred
      vision, and visual obscurations. Her exam was notable for bilateral severe
      papilledema, retinal hemorrhages, and lethargy. Her CAT scan was normal, and a
      spinal tap revealed a very high opening pressure. Although this patient's
      presentation mimicked pseudotumor cerebri, the lethargy and retinal hemorrhages
      were atypical. Her hospital evaluation was notable for elevation of the serum
      bicarbonate level, and she was subsequently found to have hypoxia and hypercapnia
      on a blood gas. The patient was diagnosed as Pickwickian syndrome, with
      obstructive sleep apnea. Treatment of the pulmonary problem resulted in dramatic
      improvement in her eye findings and her lethargy, and optic nerve sheath
      fenestration was not necessary.

PMID- 7725231
TI  - The incredible shrinking brain.
AB  - A 65-year-old white woman developed progressive visuospatial abnormalities over
      an eight-year course, secondary to Alzheimer's disease with amyloid angiopathy.
      Imaging studies demonstrated focal atrophy of the parietal and occipital lobes
      without hemorrhage. This patient manifested simultagnosia without ocular
      dysmetria or optic ataxia; hence, a true Balint's syndrome was not present. Her
      visual acuities and fields have remained stable status post-occipital lobe
      biopsy.

PMID- 7725232
TI  - Epidemiology of risk factors for age-related cataract.
AB  - Epidemiologic studies on risk factors for cataract have progressed significantly
      over the last decade. Age-related cataract is a multifactorial disease, and
      different risk factors seem to play a role for different cataract types. Cortical
      and posterior subcapsular cataracts appear to be most closely related to
      environmental stresses such as ultraviolet exposure, diabetes, and drug
      ingestion. Nuclear cataracts appear to be associated with smoking. Alcohol use
      seems to be associated with all cataract types. Consistent evidence also suggests
      that the prevalence of all cataract types is lower among those with higher
      education. Most of the current data support a role for antioxidants associated
      with decreased rates of all cataract types, but further studies are needed. More
      data are needed to establish the association, if any, of diarrhea, blood
      pressure, and use of allopurinol and phenothiazines with senile cataracts.

PMID- 7725233
TI  - Recollections of European ophthalmology in the 1940s and 1950s: a view from Albi.
AB  - The author recalls his medical/ophthalmologic education and his career and
      travels during the middle decades of this century. He provides colorful
      descriptions of his professors, friends and colleagues throughout the world,
      highlighting not only their accomplishments, but also their personalities.
      Special tribute is given to his dear friend, Dr. Edward Norton, whose death in
      July 1994 saddened many in the worldwide ophthalmic community.

PMID- 7725235
TI  - Preoperative radiographic evaluation of implant sites by computed tomography.
      Radiation dose profiles.
AB  - The purpose of the present study was to compare radiation dose profiles for one
      and two mm slice thicknesses typically used for preoperative computed tomographic
      examination of potential implant sites. A Siemens Somatom DRH CT-system was used.
      A single two mm slice absorbed only 29% of the integral dose and a single one mm
      slice, absorbed only 17% of the integral dose. This is because the radiation beam
      was unchanged between the two different examinations. The integral dose is
      therefore identical for a single one mm slice and for a single two mm slice. When
      10 consecutively two mm thick slices were exposed, approximately 50% of the
      integral dose was absorbed within the examined region. When 20 one mm thick
      slices were exposed, slightly less of the integral dose was absorbed within the
      examined region. This difference may be explained by uncertaines in the measuring
      instruments. The integral dose is, with the 10 two mm thick slices, half the
      integral dose compared to a serie of 20 one mm slices. In spite of a well
      restricted beam, more than half of the integral dose is absorbed outside the
      examined part. Consequently, during examination the thyroid gland, the eyes lens
      and the pituitary gland will be exposed to some irradiation.

PMID- 7725236
TI  - Knowledge among Swedish dentists about rules for patient records.
AB  - Some Swedish dentists chosen at random answered a questionnaire in 1992. The aim
      was to find out if the knowledge among dentists as a whole about patient record
      matters is as bad as patient records in disciplinary cases imply. The knowledge
      was good and better than expected. Specialists have a better knowledge than
      private practitioners and they also more often have a secretary to handle the
      patient records. Time of licensation and the dentist's age were of no importance.
      If the standard of knowledge in a few formal matters corresponds to a high
      standard in the observance of the rules will be investigated in the second part
      of this investigation (Rasmusson et al 1994), which will scrutinize patient
      records from the same dentists who answered the questionnaire.

PMID- 7725237
TI  - Quality evaluation of patient records in Swedish dental care.
AB  - The purposes of this study were to evaluate systematically five patient records
      each from randomly selected dentists in different regions of Sweden in 1992, and
      to see whether the good knowledge of some record-keeping rules, noted earlier,
      was reflected in practical observance of the rules as a whole. Observance was
      generally poor: in nearly 40% of the variables investigated, the documentation
      did not follow the rules. Patient history, status, diagnosis, therapy plans and
      other important information were often missing among the records from the general
      practitioners. The specialists' records, however, were in general very accurate.
      As a whole, Swedish dental patient records constitute poor antemortem material
      for forensic odontology. The dentist's age is related to the quality of the
      records. The standard of the patient records must be improved.

PMID- 7725234
TI  - Retrobulbar injections: standards of care.

PMID- 7725238
TI  - Dental assistants' ability to select caries risk-children and to prevent caries.
AB  - A new model for dental care in children has been used since 1987 in a small-town
      clinic in the county of Blekinge in southern Sweden. The model is based on early
      screening of caries risk, performed by dental assistants. The purpose is to
      obtain an individual assessment of the need of preventive dental care among pre
      school children, in order to prevent dental caries and gingivitis. The aim was to
      1) evaluate the dental assistants' selection of caries risk children up to the
      age of three by comparing dental health variables in 4 yr olds in the test clinic
      with those for the whole county and 2) compare the time spent by the dentists and
      the dental assistants in the test clinic and in the whole county per child up to
      the age of four. 102 children participated. Specially trained dental assistants
      screened children likely to develop caries lesions using background factors
      combined with clinical examinations at ages 1, 2 and 3. A systematized form for
      questioning the parents was used. Individual caries prevention was given. Dental
      health and time spent were analyzed. The proportion of children with caries
      lesions at four years and a caries risk assessment up to the age of three was
      11/19 = 0.58 (sensitivity). The proportion of children with no caries lesions at
      four years and no caries risk assessment up to the age of three was 82/83 = 0.99
      (specificity). The proportion of children with no caries lesions at 4 yr of age
      in the test clinic was 81.4% compared to a county mean of 77.2%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7725239
TI  - 6 beta-[125iodo]-3, 14-dihydroxy-17-methyl-4, 5 alpha-epoxymorphinan ([125I]IOXY
      AGO): a potent and selective radioligand for opioid mu receptors.
AB  - The recent cloning and expression of an opioid mu receptor has opened up new
      opportunities for research in opioid pharmacology. The relatively low level of
      transient receptor expression in COS cells emphasizes the need for radioligands
      with high specific activity and low nonspecific binding with which to label
      receptors. In addition, recent data indicating that agonists and antagonists bind
      to different domains on the same receptor protein indicate the utility of having
      both agonist and antagonist radioligands available for the study of opioid
      receptor mechanisms. Previous studies characterized the binding of the opioid
      antagonist 6 beta-[125iodo]-3,14-dihydroxy-17-cyclopropylmethyl-4,5 alpha
      epoxymorphinan ([125I]IOXY) and showed that this naltrexone analog labels mu and
      kappa 2 receptors in rat and guinea pig brain with high affinity and low
      nonspecific binding. In the present study, we synthesized the agonist congener of
      IOXY, 6 beta-iodo-3,14-dihydroxy-17-methyl-4,5 alpha-epoxymorphinan. We named
      this novel agent IOXY-AGO for IOXY-agonist. Competition binding studies showed
      that IOXY-AGO has high affinity for mu receptors (Ki = 0.28 nM) and lower
      affinity for delta (Ki = 18.7 nM) and kappa 1 (Ki = 33.9 nM), kappa 2a (Ki = 38.4
      nM) and kappa 2b (Ki = 58.2 nM) binding sites. IOXY-AGO was radioiodinated to a
      specific activity of 2,200 Ci/mmol. [125I]IOXY-AGO binding was rapid, readily
      reversible, and characterized by low nonspecific binding.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7725240
TI  - Cellular colocalization of dopamine D1 and D2 receptors in rat medial prefrontal
      cortex.
AB  - In a recent study in rat medial prefrontal cortex (mPFC), a fluorescently
      coupled, high-affinity ligand for the D1 receptor subtype was localized to
      nonpyramidal neurons, while a ligand selective for the D2 subtype was found on
      neurons with a size distribution overlapping with both small pyramidal and large
      nonpyramidal cells. These observations raised the possibility that a
      subpopulation of cortical neurons with an intermediate size range may coexpress
      both the D1 and D2 receptor subtypes. In the present study, the D1 and D2
      receptor subtypes have been simultaneously localized in layer VI of rat mPFC
      using 20 nM SCH 23390-Bodipy and 20 nM N-(p-aminophenethyl) spiperone-Texas red,
      respectively, in the presence of 100 nM mianserin (5-HT2 receptor antagonist).
      The localization of receptor binding fluorescence was assessed in paired images
      using fluoroscein isothiocyanate (FITC) and rhodamine dichroic filters for the D1
      and D2 subtypes, respectively. Under the conditions employed here, most cell
      bodies showed either D1-like or D2-like receptor binding fluorescence, while a
      colocalization of both fluoroprobes was observed on only 25% of the labeled
      cells. When the size of each single-labeled cell body was measured using the
      respective FITC (D1-probe) and rhodamine (D2-probe) epifluorescence filters, the
      distribution of cells showing only D1-like receptor binding fluorescence was
      similar to nonpyramidal neurons (68.6 +/- 1.8 microns 2), while that for cells
      showing only D2-like receptor binding fluorescence was similar to that of both
      large interneurons and small pyramidal cells (106.9 +/- 2.4 microns 2).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7725241
TI  - Different mechanisms may be required for maintenance of NMDA receptor-dependent
      and independent forms of long-term potentiation.
AB  - In hippocampal area CA1, long-term potentiation (LTP) is induced by tetanic
      stimulation protocols that activate N-methyl-D-aspartate (NMDA) receptors. In
      addition, some stimulation protocols can induce LTP during NMDA receptor
      blockade. An initial signal in both NMDA receptor-dependent and independent LTPs
      is increased intracellular Ca2+ concentration in postsynaptic neurons. It
      therefore seems possible that subsequent steps leading to expression and
      maintenance of potentiation are shared whether or not LTP is induced through NMDA
      receptor activation. We tested this hypothesis by applying a broad spectrum
      protein kinase inhibitor, previously shown to inhibit NMDA receptor-dependent
      LTP. In agreement with earlier reports, we found that H-7 inhibited NMDA receptor
      dependent LTP when applied either during tetanic stimulation, or beginning 30 min
      following tetanic stimulation. In contrast, NMDA receptor-independent LTP was not
      inhibited by H-7 applied during or following tetanic stimulation. We also tested
      for mutual occlusion between NMDA receptor-dependent and independent LTPs.
      Although induction of NMDA receptor-independent LTP did not occlude later
      induction of NMDA receptor-dependent LTP, induction of NMDA receptor-dependent
      LTP did occlude NMDA receptor-independent LTP. While the kinase inhibitor
      experiment showed a clear difference between NMDA receptor-dependent and
      independent LTPs, the occlusion experiments suggest an interaction between the
      signalling pathways for the two LTPs.

PMID- 7725242
TI  - Anatomical localization of SKF-38393-induced behaviors in rats using the
      irreversible monoamine receptor antagonist EEDQ.
AB  - This study was designed to localize the population of dopamine D1-like receptors
      involved in grooming and oral movements elicited by systemic administration of
      the D1-selective agonist SKF-38393. Receptors in specific dopamine terminal
      regions were inactivated by intracranial injection of the nonselective
      irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ).
      The effect of these injections on behaviors induced by systemic administration of
      SKF-38393 (10 mg/kg) was measured 48 hours later. The specific populations of D1
      like receptors inactivated by the EEDQ injections were identified as a loss of 3H
      SCH-23390 binding in a given region using quantitative autoradiography. EEDQ (1.5
      micrograms/microliters/side) injected into the nucleus accumbens (NAc) did not
      alter SKF-38393-induced behaviors. Similarly, injection of EEDQ into the medial
      caudate-putamen (CPu) failed to alter these behaviors. In contrast, EEDQ (0.15
      1.5 micrograms/microliters/side) injected into the lateral CPu decreased both SKF
      38393-induced grooming and oral movements, with complete blockade of grooming
      observed at the highest dose. To determine whether this effect of EEDQ was due to
      inactivation of D1-like receptors, separate groups of animals were pretreated
      with SCH-23390 (3 mg/kg, S.C.) 15 min prior to injection with EEDQ. Pretreatment
      with SCH-23390 prevented the disruption of SKF-38393-induced behaviors, as well
      as the loss of 3H-SCH-23390-labeled binding sites observed after injection of
      EEDQ into the lateral CPu. EEDQ injections that produced disruption of SKF-38393
      induced behaviors were associated with a greater loss of binding in the lateral
      CPu relative to other regions examined including the NAc, medial CPu, and globus
      pallidus. Furthermore, EEDQ injections that produced the greatest loss of 3H-SCH
      23390 binding in the latter three regions did not disrupt SKF-38393-induced
      behavior. These results demonstrate that stimulation of D1-like receptors in the
      lateral CPu is necessary for behaviors induced by systemic administration of SKF
      38393. The results also demonstrate the utility of this "receptor lesion"
      technique to localize receptor-mediated behaviors.

PMID- 7725243
TI  - How can exocytosis account for the actual properties of miniature synaptic
      signals?
AB  - It is broadly accepted that a postsynaptic "miniature" is the most elementary
      chemically transmitted signal and results from the all-or-none release of
      transmitter packaged in a single presynaptic vesicle. Hitherto, it has not been
      possible to directly verify this renowned representation, although it is
      consistent with evidence of vesicle traffic and, following an intense period of
      release, vesicle depletion. However, vesicle traffic involving molecular
      components similar to those implicated in transmitter release has been attributed
      to other functions including membrane repair. Furthermore, as a number of
      investigators have recently proposed, miniature signals recorded at peripheral
      and central synapses may actually reflect several rather than a single discharge
      of transmitter. It is not clear whether such putative multiple-discharge
      miniatures represent near-synchronous exocytoses of several vesicles or a burst
      of openings in a pore that couples a vesicle with the outer membrane. In any
      case, despite the popularity of the vesicular hypothesis, the molecular mechanism
      involved in synchronizing fast elementary secretion has not yet been elucidated.
      Interdependencies among subminiature discharges composing a miniature have
      suggested that the underlying process is a regenerative signal restricted to a
      presynaptic terminal unit, confirming Fatt and Katz's first speculation on
      miniatures, which was not vesicular exocytosis [Fatt and Katz (1952), J.
      Physiol., 117:109-128]. Here we discuss the possibility that this regenerative
      signal might be a localized cytosolic Ca2+ transient and attempt to reconcile
      this hypothesis with the exocytotic models proposed to explain fast transmitter
      release.

PMID- 7725245
TI  - Modulation of GABAA receptor binding in human brain by neuroactive steroids:
      species and brain regional differences.
AB  - Allosteric modulation by neuroactive steroids of radioligand binding sites on the
      GABAA receptor complex was demonstrated by autoradiography in vitro in several
      regions of human brain and the effects compared to those in rat brain. Comparing
      human and rat, two steroids known to be active in enhancing GABA-mediated
      postsynaptic inhibition, 5 alpha-pregnane-3 alpha,21-diol-20-one (tetrahydro
      deoxycorticosterone, THDOC) and alphaxalone (5 alpha-pregnane-3 alpha-hydroxy
      11,20-dione), allosterically inhibited [35S]T-BPS binding to the
      picrotoxin/convulsant site in both species in several regions including the
      hippocampus. Unlike rat, human brain binding of [3H]flunitrazepam to the
      benzodiazepine site was not enhanced by alphaxalone (at any concentration), but
      was unaffected in many regions and inhibited in others. Binding of [3H]muscimol
      to high and low affinity GABA sites were enhanced by both steroids in all tested
      regions of rat brain, although to varying degrees. However, several lobes of
      human cortex showed no modulation of muscimol binding by either steroid, and
      THDOC, but not alphaxalone, inhibited in some areas. Comparing regions, THDOC at
      high concentrations (10 microM) enhanced in human frontal lobe and primary
      sensory and motor cortex, with greater effect in deep layers than superficial.
      This steroid had no effect in other parts of parietal lobe and inhibited muscimol
      binding in temporal lobe, primary visual cortex, and other parts of occipital
      lobe. Concentration-dependence curves for THDOC showed regional variation, e.g.,
      in the hippocampal formation and surrounding neocortex. These regional and
      species differences are consistent with the existence of multiple GABAA receptor
      subtypes that differ in pharmacology. This heterogeneity provides both the
      opportunity and the difficulty of targeting clinically useful medications such as
      antiepileptic drugs to the appropriate human brain regions, and the species
      differences in regional subtype expression suggest caution in use of animal
      models.

PMID- 7725244
TI  - Evidence against differential release of noradrenaline, neuropeptide Y, and
      dopamine-beta-hydroxylase from adrenergic nerves in the isolated perfused sheep
      spleen.
AB  - The subcellular storage and release of noradrenaline (NA), dopamine-beta
      hydroxylase (D beta H), and neuropeptide Y (NPY) was studied in the isolated
      perfused sheep spleen. Subcellular distribution studies showed a bimodal
      distribution for NA which was well reflected by D beta H and indicated the
      occurrence of two types of NA storage vesicles. The most dense, presumably large
      dense-cored vesicles (LDV), contain both membrane-bound and soluble D beta H; the
      less dense presumably corresponds to small dense-cored vesicles (SDV) and at
      least does not contain soluble D beta H. The distribution of NPY is extended but
      shows a peak only at the position of LDV, indicating that LDV contain NPY.
      Continuous electrical stimulation of the splenic nerve at 2 Hz, 5 Hz, 10 Hz, and
      20 Hz or at 20 hz with bursts induced the release of NA, NPY, and D beta H. The
      ratio among these components was constant. The fractional release of D beta H and
      NA was comparable at all frequencies used; that of NPY was 10-20 times lower,
      suggesting the occurrence of a large nonreleasable NPY pool. The present data
      argue against a high frequency stimulation or intermittent stimulation-induced
      preferential release of NPY from adrenergic neurons and question the concept of
      frequency-dependent chemical coding of sympathetic transmission in general. The
      simplest interpretation of our data is that NA and NPY are released at all
      frequencies from a single pool. The present finding might signify that only large
      dense-cored vesicles are involved in the sympathetic stimulation-evoked secretion
      of catecholamines from adrenergic nerve terminals of the isolated sheep spleen.

PMID- 7725246
TI  - Effect of injury on the bi-affinity alpha 1-adrenoreceptor binding in rat brain
      in vivo.
AB  - Focal freezing lesions in rats cause a widespread decrease of cortical glucose
      utilization in the lesioned hemisphere, probably as a reflection of depressed
      cortical activity. The noradrenergic neurotransmitter system was implicated in
      these alterations when it was demonstrated that prazosin, a specific
      norepinephrine (NE) antagonist at alpha 1-adrenergic receptors, prevented their
      development. In normal rat brain, specific binding of [125I]HEAT [(+/-)2-(3
      [125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone], another selective alpha
      1-adrenoreceptor ligand, was demonstrated in vivo at sites consistent with the
      alpha 1A- and alpha 1B-adrenoreceptor subtypes. In the present study, the effect
      of a freezing lesion on specific binding of [125I]HEAT in rat brain in vivo was
      determined three days after traumatization when cortical glucose use suggested
      the greatest degree of functional depression. The steady-state volumes of
      distribution of [125I]HEAT three days after injury were significantly increased
      in all the cortical areas of the lesioned hemisphere, but not in the subcortical
      structures. Injury did not modify the binding affinities for HEAT. However, a
      statistically significant increase in the number of low-affinity binding sites
      for this ligand was demonstrated in all cortical areas of the lesioned
      hemisphere, but not in subcortical structures. The traumatization did not modify
      Bmax estimates for the high-affinity binding of HEAT. The results support the
      hypothesis that changes in the noradrenergic system are of functional importance
      in brain injury and that at least some effects of injury are mediated by alpha 1B
      adrenergic receptors.

PMID- 7725247
TI  - Protective effects of MK-801 on methamphetamine-induced depletion of dopaminergic
      and serotonergic terminals and striatal astrocytic response: an
      immunohistochemical study.
AB  - It has been shown previously that methamphetamine induces dopaminergic nerve
      terminal degeneration, serotonin depletion and striatal reactive astrogliosis,
      and that the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 can
      block methamphetamine (MA)-induced depletion of dopamine and serotonin and
      reduction in activity of their synthetic enzymes. In this study,
      immunohistochemistry was used to evaluate the effect of MK-801 on methamphetamine
      induced neuropathological alterations of dopaminergic and serotonergic terminals
      and striatal astrocytic responses. Adult male rats were treated with
      methamphetamine (4 injections of 10 mg/kg at 2 hour intervals) in conjunction
      with MK-801 which was administered 15 min before each methamphetamine
      administration at doses of 1 mg/kg or 2 mg/kg. Brains were examined three days
      following treatment. MK-801 administration prevented methamphetamine-induced
      depletion of 5-hydroxytryptophan (5-HT) terminals in the forebrain and depletion
      of tyrosine hydroxylase-positive dopaminergic terminals and astrocytic response
      in the neostriatum in most animals. These results support the concept that
      excitatory amino acids acting through an NMDA receptor are involved in
      methamphetamine-induced neuronal damage on dopaminergic and serotonergic terminal
      fields. A minor depletion of TH-positive terminals and astrogliosis in the
      neostriatum was seen in three of nine MA-MK-801-treated animals. This indicates
      that the protective effects of MK-801 on MA-induced dopaminergic terminal
      degeneration varies among animals with complete protection in most animals and
      partial protection in the others using the present doses and dosing regimen.

PMID- 7725248
TI  - [The echographic assessment of the activity of the inflammatory process in
      patients with chronic acalculous cholecystitis in the choleretic test].
AB  - Ultrasonic investigations of the gallbladder in choleretic test were carried out
      in 186 patients with chronic acalculous cholecystitis (CAC): 47 with intensive,
      76 with moderate and 31 with minimal exacerbation, 32 patients in remission and
      36 control subjects. As shown by choleretic test, a reduction of latent period
      and gallbladder contraction duration, a decrease in discharged bile amount, bile
      discharge velocity, initial and final gallbladder volumes' ration and increased
      final gallbladder volume occurred in CAC patients. These changes were parallel to
      inflammation intensity. Three types of gallbladder contraction were revealed in
      choleretic test: a 3-phase contraction curve with the initial fast evacuation
      period, relaxation wave (enlarged gallbladder) and slow evacuation period (type
      1); a 2-phase curve with fast and slow evacuation (type 2); a monophasic curve
      with slow evacuation (type 3). In the patients studied type 1 prevailed, while
      type 3 was not observed in the controls. With increasing inflammation activity in
      CAC patients a type-1 contraction frequency declined and disappeared in active
      exacerbation, whereas type 2 and especially type 3 contractions became more
      frequent.

PMID- 7725249
TI  - [The characteristics of the development of gallbladder and biliary tract
      pathology under the influence of vibration].
AB  - The examination of 86 helicopter pilots has shown that their exposure to
      vibration leads to biliary and gallbladder damage which aggravates with longer
      service. As indicated by spectroscopy and gas-liquid chromatography, vibration
      affects colloid-osmotic properties of bile: molecules grow in size, bile acids
      retention becomes longer.

PMID- 7725251
TI  - [The mental status characteristics of patients with peptic ulcer and chronic
      cholecystitis].
AB  - Mental status examinations (V. P. Zaitsev's clinical scale. MMPI test modified by
      F. B. Berezin et al.) were performed in 90 patients with duodenal ulcer (DU) and
      142 patients with chronic acalculous cholecystitis (CAC). Mental changes were
      revealed in 93.3% and 86.6% of DU and CAC patients, respectively, in the disease
      aggravation. These changes persisted more continuously in CAC patients as they
      remained after the disease treatment unlike those in DU. Therefore, mental status
      of CAC patients needs correction.

PMID- 7725250
TI  - [The interdigestive phasic motility of the gallbladder and bile excretion in
      healthy subjects and in patients with duodenal peptic ulcer].
AB  - Interdigestive phasic motility of the gallbladder and bile excretion into the
      duodenum were studied in 100 patients with duodenal ulcer (DU) and 20 healthy
      subjects. Gall bladder motility and bile excretion in both healthy and DU
      subjects directly depended on interdigestive phasic activity of the duodenum and
      gastric antrum. In health, gallbladder volume reached its maximum within
      termination of phase II, minimum in the end of phase III-beginning of phase I.
      Maximal bile production occurred at phase II-III and coincided with pH decline in
      the stomach. The mixture of the vesicular and duct bile flowed out in the end
      phase III-beginning of phase I. The range of volumetric bladder contraction made
      up 33% of its capacity. In DU patients this reached 35%, the bladder capacity was
      reduced, the maximum bile production occurred at phase II, bile flowed out
      intermittently, its color changed from achromatic to dark yellow. The latter fact
      suggests hypertensive and hypermotor dyskinesia of the gallbladder as well as its
      sphincter system and bile duct functional impairment. This requires adequate
      therapeutic correction with consideration of relevant motor and secretory
      disturbances.

PMID- 7725252
TI  - [The characteristics of the present-day course of peptic ulcer in childhood and
      the approaches to the staged treatment of patients].
AB  - A prospective clinico-epidemiological trial entered 13000 children and 1432 ulcer
      pediatric patients. The data were obtained on the disease prevalence, structure
      and risk factors. Childhood ulcer is shown to affect more children, to occur at
      younger age, to become more serious. Differentiation was carried out of clinico
      paraclinical manifestations of ulcer depending on ulcer location. Individual
      approaches are promoted to treatment of patients in outpatient, inpatient and
      sanatorium settings.

PMID- 7725253
TI  - [The drug prophylaxis of peptic ulcer exacerbations].
AB  - 453 patients with ulcer located in the duodenal bulb and pyloric part of the
      stomach in the presence of Helicobacter pylori were examined before and followed
      up after hospital treatment of the ulcer. The authors findings support the
      importance of maintenance with current antisecretory drugs and on-demand therapy
      as well as of combined antibacterial therapy against Helicobacter pylori.
      Adequate chemotherapy in the ulcer exacerbation was able to reduce the number of
      recurrences and complications.

PMID- 7725254
TI  - [The efficacy of pharmacotherapy in patients with chronic liver pathology and the
      function of the antioxidant defense enzymes].

PMID- 7725256
TI  - [Esophageal function based on esophageal manometric data in cardiospasm].

PMID- 7725258
TI  - [Lipid peroxidation and the antioxidant system in chronic cholecystitis in
      persons located in an area of increased radiation].
AB  - The studies covered 35 subjects with chronic cholecystitis who had to work in
      radionuclide-contaminated territory. There appeared changes in examinees' lipid
      peroxidation and antioxidant defense systems. These were more pronounced in
      leukocytes, possibly due to direct action of radiation on cell membrane, and may
      contribute to disease chronicity and recurrences.

PMID- 7725255
TI  - [The clinico-morphological characteristics of the nonulcerative dyspepsia
      syndrome].
AB  - The examination of 453 new cases of young-age gastroduodenal affections
      demonstrates that two-thirds of the patients have non-ulcerative dyspepsia
      presenting as a symptom complex associated with heterogeneous group of gastric
      and duodenal diseases with specific pathomorphological alterations in the absence
      of ulcers and cancer. The problem of nonulcerative dyspepsia needs further
      detailed specification studies.

PMID- 7725257
TI  - [Anthropogenic sources of radiation hazards].

PMID- 7725259
TI  - [The characteristics of the morphological changes in the digestive canal, the
      clinical course of digestive organ diseases and the immune status of persons
      subjected to radiation exposure as a result of the accident at the Chernobyl
      Atomic Electric Power Station].

PMID- 7725260
TI  - [The characteristics of the prevention of HB viral infection in hemodialysis
      units].
AB  - Patients and medical personnel of some hemodialysis centres of the north-west
      region of the Russian Federation were examined for HB-virus infection markers
      using enzyme immunoassays. Subjects free of HB markers were immunized with
      ENGEPIX-B vaccine. Immunogenicity of the vaccine was assessed one month and one
      year after the immunization. Epidemiological HB factors in hemodialysis centers
      were studied on the simulation computer model. HB-virus-containing blood
      transfusion factor is not the only determinant of HB-virus infection prevalence.
      The virus can be transmitted via hemodialysis facilities. Immunization effects
      proved inferior in the hemodialysis unit patients. It is stated that
      vaccinoprophylactic policy in the patients of the dialysis centers and relevant
      equipment need serious improvement to prevent hepatitis B outbreaks.

PMID- 7725261
TI  - [Blood phospholipids in patients with different clinical manifestations of
      chronic glomerulonephritis and preserved kidney function].

PMID- 7725265
TI  - [A case of the development of a chronic internal interintestinal fistula].

PMID- 7725263
TI  - [Cisapride and other prokinetic agents in the treatment of gastroenterological
      diseases].

PMID- 7725266
TI  - [A case of a combination of acute myelomonoblastic leukemia with pulmonary
      tuberculosis].

PMID- 7725262
TI  - [The correction of the hemodynamic disorders in patients with IHD complicated by
      intraventricular blocks by using beta-adrenergic agents].
AB  - Basing on ECG findings, the authors compare hemodynamic effects of a single dose
      of isadrin, obsidan and spesicor in patients with coronary heart disease
      complicated by bundle-branch block. Isadrin improves left ventricular
      contractility, reduces pulmonary hypertension and right heart overload. Obsidan
      and spesicor aggravate the existing hemodynamic disorders in the above patients.

PMID- 7725264
TI  - [The enhancement of treatment efficacy in chronic liver failure by using
      hemoperfusion across donor hepatocytes and spleen fragments].
AB  - Hemoperfusion via donor hepatocytes and splenic fragments is an effective
      adjuvant method of treatment of hepatic insufficiency, especially in patients
      with autoimmune disease. Hemoperfusion effect occurs due to normalization of
      mesenchymoinflammatory and immunological indices as a result of positive action
      of hepatotropic and immunotropic factors of the spleen. The highest effectiveness
      of the above hemoperfusion is reached in its early use, that is before the
      disease becoming chronic.

PMID- 7725267
TI  - [A. A. Ostroumov--on the 150th anniversary of his birth].

PMID- 7725268
TI  - [The echographic and biochemical signs of liver and splenic involvement in
      patients with aplastic anemia].
AB  - Sonography of the liver, gallbladder, portal and splenic veins, biochemical
      hepatic tests were conducted in 35 patients with aplastic anemia (AA). The
      patients were ill from 3 months to 20 years. Depending on AA, duration some
      patients displayed a small enlargement of the liver, changes in its echo
      structure, increased calibre of the portal veins. Moderate hepatomegaly was
      associated with biochemical shifts reflecting dysfunction of hepatic tissue. The
      above sonographic and biochemical changes observed usually in toxic hepatitis
      result from different chemical compounds produced within AA genesis, from
      administration of anabolic hormones and other drugs, frequent transfusion of red
      cells and other blood components. The size of the spleen was not changed, though
      its echo pattern was abnormal.

PMID- 7725269
TI  - [Acute aortic dissection].

PMID- 7725270
TI  - [Acute aortic dissection].
AB  - The acute aortic dissection is a relatively rare event carrying a grave
      prognosis. It is the most common fatal condition involving the aorta. A high
      index of suspicion is mandatory because of a mortality rate of 1 to 2% per hour
      in the first 48 hours. A recent series from the Mayo Clinic using modern
      diagnostic methods showed that in 62% of the patients the initial impression of
      aortic dissection was correct, but in 28% this diagnosis was only made post
      mortem. The clinical suspicion arises from a history of sudden severe pain in the
      chest or the back, sometimes wandering downwards, and from certain clinical
      findings like aortic regurgitation, pulse deficits or neurologic manifestations
      such as cerebrovascular accidents or ischemic paraparesis. ST-segment elevation
      in the ECG is very unusual in aortic dissection and should direct the clinical
      focus to acute myocardial infarction. Large-bore peripheral venous access should
      be established, and pain control should start immediately. Hypertensive patients
      should be treated first with an intravenous beta-blocking agent. Vasodilators
      increase aortic wall stress, they should only be administered after a beta
      blocking agent. Transfer to a hospital with appropriate diagnostic and surgical
      is mandatory.

PMID- 7725271
TI  - [Acute pulmonary embolism].
AB  - Pulmonary embolism is a frequent event, even today the diagnostic comes often too
      late or not at all. Symptoms, clinical results and additional examinations like
      ECG, echocardiography, scintigraphy and angiography permit the differentiation
      between small peripheral and massive central pulmonary embolism [PE], important
      for the therapeutic procedure. Patients with peripheral PE have to be
      heparinized, sometimes they can be treated at home. The acute massive PE
      represents an emergency situation, the patient must be hospitalized immediately.
      The goals of therapy in massive PE consist in a rapid reduction of the
      threatening load on the right ventricule by the embolism. If the patient is in
      cardiogenic shock, surgical embolectomy is indicated, without shock the immediate
      start of thrombolytic therapy must be considered.

PMID- 7725272
TI  - [Acute vertigo].
AB  - Among all patients presenting with acute vertigo, majority will be suffering from
      benign paroxysmal positional vertigo, vestibular neuritis or Meniere's disease.
      One of the most important central vestibular disorder that imitates labyrinthine
      dysfunction is vertebrobasilar artery disease. To differentiate this condition
      from peripheral vestibular lesions, particular attention should be directed to
      the type of nystagmus which is present. Additionally, duration of vertigo and
      further neurological symptoms and signs are crucial for correct localization and
      etiology of the underlying disorder.

PMID- 7725273
TI  - [Diarrhea, coli infection, septic encephalopathy: escalation of a seemingly banal
      symptom].
AB  - Septic encephalopathy is an early manifestation of sepsis. Changes in
      consciousness, focal or generalized seizures, multifocal myoclonus and/or varying
      hemiparesis are common clinical findings. All of these symptoms are reversible
      when sepsis has been successfully treated. Because there are no generally
      accepted criteria for the diagnosis of septic encephalopathy, it is a diagnosis
      of exclusion. We report the case of a 68-year-old patient who developed septic
      encephalopathy secondary to diarrhea and E. coli sepsis. In this case, symptoms
      of septic encephalopathy were fully reversed after the patient's E. coli sepsis
      had been adequately treated.

PMID- 7725274
TI  - [Ethanol ingestion following Antabus overdose: acetaldehyde-induced cardiological
      emergency].
AB  - The differential diagnosis of chest pain is challenging, when the clinical
      presentation appears pathognomonic, yet conventional diagnostic tests fail to
      reveal the suspected cause. We report the case of a 38-year-old patient who had
      an acetaldehyde intoxication (antabuse syndrome) in the setting of disulfiram
      overdose and ethanol ingestion. The patient presented with severe angina
      pectoris. Coronary artery disease was suspected, because the patient had risk
      factors and electrocardiographic repolarization changes were present. During the
      further investigation it became evident that symptoms were solely caused by
      acetaldehyde intoxication following disulfiram and alcohol ingestion. Toxic
      levels of acetaldehyde were found in the patient's serum. Coronary artery disease
      was ruled out by cardiac catheterization.

PMID- 7725275
TI  - [Acute glaucoma attack].
AB  - An acute angle-closure glaucoma is thought of as a sudden, mostly unilateral
      marked increase in intraocular pressure. The patient complains of strong,
      sometimes radiating pain as well as a reduction in visual acuity. The affected
      eye is severely reddened, the cornea is cloudy, and the ocular globe feels rock
      hard under palpation. Immediate therapy is decisive for maintaining visual
      function. In an acute case, therapy should include local pressure-reducing eye
      drops and systemic diuretics. Surgical intervention should always be made to
      prevent repeated occurrence and as a prophylaxis in the partner eye.

PMID- 7725276
TI  - [Emergency therapy of burns].
AB  - Burns are among the most common accidental injuries, occurring in almost any
      environment to victims of all ages. Most of them are minor injuries and may be
      treated on an out-patient basis. Superficial (first-degree and superficial second
      degree) burns will heal uneventfully in about two weeks without scarring, as long
      as no infection complicates the healing process. Major burns, however, are life
      threatening, and professional treatment is crucial for survival. The intensive
      care and the surgical treatment in these patients demand a major commitment in
      terms of personnel and material resources; in addition, emotional reactions by
      any person involved in the case are not uncommon. A skilled and knowledgeable on
      scene emergency treatment may diminish the depth of the burn wound and will
      furthermore reduce the number of complications like hypovolemic shock and
      infection. A complete clinical assessment including the patient history gives the
      rationale for any therapy and will help determine the appropriate referral
      center. The emergency treatment primarily includes the cooling of the burn wound
      to stop the burning process and to reduce pain, the insertion of an intravenous
      line, including the infusion of 1 to 2l of an isotonic electrolyte solution per
      hour, and the management of pain with intravenous boluses of morphine. The
      patient should also receive supplemental oxygen, and the burn wound should be
      covered by sterile drapes. Finally, every burn victim requires tetanus
      prophylaxis. Major burns and burn wounds at sensitive locations such as head and
      hands should be treated in specialized burn centers. This provides best chances
      for survival and increases the probability for a good cosmetic result.

PMID- 7725277
TI  - [Panic disorders in the emergency room].
AB  - Patients with panic disorder perceive physical symptoms which they interpret as
      dangerous phenomena; therefore, they normally seek help from physicians in
      somatic medicine and do not consult with a psychotherapist or psychiatrist. The
      combination of physical symptoms and catastrophic thinking induces such an
      intense feeling of anxiety that patients often visit an emergency unit. Thus, the
      prevalence of panic disorder is high among patients who seek help for heart
      symptoms within the setting of an emergency department (18%); in other clinical
      populations it may even be higher (patients with negative coronary angiography 33
      to 59%, with irritable bowel syndrome 29 to 38%, with migraine headache 5 to
      15%). Already in the emergency department it is possible to establish with the
      patient an understanding of the impact such catastrophic interpretations of
      basically benign physical changes have on the development of panic. This helps to
      avoid long-standing and expensive patient careers that have often been described
      in the literature. The present review includes a description of the cognitive
      model of the origin and the treatment of panic disorder as well as an overview of
      drug treatments with benzodiazepines and antidepressive drugs.

PMID- 7725278
TI  - [Emergencies in ORL practice].
AB  - Emergencies are frequent in the everyday ENT outpatient clinic. From a great
      variety of emergencies only the most frequent ones were outlined, such as
      epistaxis, acute unilateral deafness, injuries of the tympanic membrane, foreign
      bodies events and acute external otitis. The clinics, etiology and therapy are
      discussed in order to help the general practitioner to cope with emergencies in
      the ENT field.

PMID- 7725279
TI  - ["The new North"--a schizoid disorder?].

PMID- 7725280
TI  - [The electronic hospital record--will it be realized?].

PMID- 7725281
TI  - [Back to a more health-oriented narcotic policy?].

PMID- 7725282
TI  - [Mortality among drug addicts in Norway].
AB  - Current drug abusers in Norway seem to differ from those of 25-30 years ago in
      several respects, namely with regard to selection to drug abuse, living
      conditions, and the social responses to drug abuse. These factors may all be
      relevant for morbidity and mortality. Mortality and excess mortality under the
      age of 50 was assessed on the basis of data on 1,491 drug abusers admitted to the
      National Clinic for Drug Abusers (Statens klinikk for narkomane) during the years
      1961-91. A significant excess mortality among the drug abusers was found for both
      genders, in all age groups and for all three decades. Males displayed a higher
      mortality than females, and the mortality among drug abusers increased with
      increasing age. Excess mortality was higher for women than for men and decreased
      with increasing age. The most prevalent causes of death were overdoses, suicides
      and accidents. Mortality from overdoses and diseases was higher among persons
      admitted during the 1970s and 1980s compared with persons admitted during the
      1960s. The results are discussed in light of the qualitative differences between
      the former and present populations of drug abusers in Norway.

PMID- 7725283
TI  - [What nobody thought possible--a "demobilization chain" gone astray. Foreign body
      in the urinary bladder--a current differential diagnosis].
AB  - Intravesical foreign bodies should be considered in cases of unexplainable lower
      urinary tract symptoms or recurrent urinary tract infections with therapy
      resistant microbes like Proteus mirabilis and Pseudomonas. Usually these
      conditions are due to accidents in genitourinary surgery or instrumentation, but
      in our case occurred as a complication to an erotic procedure. This paper
      describes a case with a so-called "dimme-lenke", i.e. a chain used to count down
      days until demobilization from compulsory military service for Norwegian
      recruits, found in the bladder of a 13-year-old boy. A knot at the end of the
      chain made endoscopic removal impossible and it had to be removed by cystotomy.

PMID- 7725284
TI  - [From a registry to a clinical information system. Development of the Datacor
      system at the surgery department A, Rikshospitalet].
AB  - Based on a simple register for thoracic and cardiovascular operations a modulated
      system has been built up at Department of Surgery A. The register covers waiting
      list, a basic patient record, extensive operative data, the postoperative course
      and the final outcome. A local area network includes 36 microcomputers with
      approximately 75 users. Owing to lack of commercially available programs, local
      applications based on dBase have been developed. In this article we discuss our
      positive experiences from use of the local system with respect to administration,
      quality assurance and local research, its future place within a larger hospital
      system interconnected via a backbone, the need for better support and graphic
      user interface.

PMID- 7725285
TI  - [Fall-related injuries among elderly at home].
AB  - The aim of this study was to describe the extent of the problem of injuries from
      falling among elderly people at home. The study is based on data from the
      National Injury Register, which contains information on all inpatients and
      outpatients treated for injuries by hospitals and emergency clinics in four
      Norwegian towns. This study included 594 cases of accidental fall-related
      injuries which occurred at home in 1992 among a total population of 23,942
      persons aged 65 years and over living in two towns, Drammen and Stavanger. The
      incidence of fall-related injuries at home was 25 per 1,000. The incidence was
      higher among women than men (32 and 13 per 1,000 respectively). The ratio between
      falls to the same level and falls to lower levels was 2:1 in the age group 65-79
      year and 4:1 in the age group over 80 years. The most common mechanisms causing
      injuries were loss of balance (46%), stumbling (19%) and sliding (12%). 60% of
      all patients sustained fractures (15 per 1,000). 50% of all patients were
      hospitalised. The findings show that possibilities exist for preventing these
      injuries. The strategies must be directed both at the home environment and at
      individual factors among the elderly population.

PMID- 7725287
TI  - [Traditional and non-traditional curricula. Definitions and terminology].
AB  - Differences between traditional (conventional) and innovative curricula are
      described. Technical terms are defined or explained. In traditional tracks, basic
      and clinical sciences are studied separately. The students meet the first patient
      after several years. The education is mainly discipline-, teacher-, lecture- and
      hospital-based. In innovative programmes, basic sciences are taught throughout
      the study parallel with clinical subjects (vertical integration), and subjects
      from related disciplines are often taught concurrently (horizontal integration).
      The students meet patients from the first day at the university, participate from
      the first week in courses in clinical skills, and, after some months, attend
      continuity clinics in the community. Teaching is student-directed, problem-based
      and/or community-oriented, with several electives. Many of the strategies above
      are also used in traditional curricula. The main difference between traditional
      and innovative curricula is whether basic and clinical sciences are vertically
      integrated or not.

PMID- 7725286
TI  - [Medical emergency service. Descriptions of a one-year activity at an emergency
      communication center].
AB  - The emergency medical communication centre, Vestfold Central Hospital, receives
      emergency medical calls (phone 113), from 200,000 citizens in Vestfold county.
      Calls are categorised by urgency (red, yellow or green) according to the
      Norwegian Index to Emergency Medical Assistance, a criteria-based dispatch
      manual. In 1993, 2,440 red (suspected life-threatening conditions), 3,502 yellow
      and 6,505 green calls were received. The frequency of red and yellow calls did
      not differ much through the day, but varied between different municipalities in
      the county. The cause of emergencies varied by month. Acute illness increased in
      May and December, accidents in June, July and December. Psycho-social emergencies
      (violence, suicide, drug abuse) seemed to vary in a circadian manner. Efforts
      were made 628 times to give basic life support instruction by telephone. An
      ambulance was the most frequent response, general medical practitioners were
      called upon relatively seldom. The response was estimated to adequate in 79% of
      the incidents, exaggerated in 9% and inadequate in 3%.

PMID- 7725288
TI  - [Medical practice in Vestlandet at the turn of the century].

PMID- 7725290
TI  - [Sleep disorders].
AB  - There has been a great development in sleep medicine during the past 20-25 years
      and the International Classification of Sleep Disorders now lists about 90
      relatively well-defined conditions related to sleep. Several of them are severely
      underdiagnosed. This review considers frequent and/or disabling sleep disorders,
      in particular disorders for which treatment is available.

PMID- 7725289
TI  - [Alcohol--bad for the brain?].
AB  - The consumption of alcohol and other addictive drugs is quite low in Norway
      compared with other European countries. Nevertheless, many will experience some
      of the various drug effects on the brain. Alcohol, the legal substance, is
      responsible for most drug-related neurological effects in Norway. Alcohol use
      results in a variety of different effects in different parts of the central
      nervous system. Headache and alcohol withdrawal symptoms are frequent complaints,
      and atrophy of the cerebellar vermis and Wernicke Korsakoff syndrome often result
      in chronic sequelae. Most other drugs cause less structural damage to the nervous
      system than alcohol does. Clinical findings, pathogenetic mechanisms and
      treatment of some drug-related neurological disorders are discussed.

PMID- 7725291
TI  - [Insomnia and hypnotics].
AB  - This article outlines some of the new developments in the field of insomnia. To
      obtain a better understanding of insomnia and avoid the diversities of
      impractical diagnosis, the medical profession must universally agree on the
      classification of insomnia. This knowledge has to be available to all levels of
      the medical community, especially general practitioners. The article reviews some
      new data about classification, diagnosis, and treatment of insomnia. It discusses
      the definition of insomnia and sets up the accepted criteria for the severity of
      its various forms. The policy of using hypnotics in Norway is fairly restrictive.
      Only three hypnotics are available, two benzodiazepins (nitrazepam and
      flunitrazepam) and the newly introduced cyclopyrrolone (zopiclone). The
      mechanisms of action of various hypnotics on the gamma-aminobutyric acid system
      are briefly discussed, and guidelines are given for use and choice of hypnotics,
      their indications and contraindications. In any modern society like Norway, there
      should be a clear awareness of the impact of insomnia on the quality of life and
      the seriousness of the effects it can have on the everyday activities of subjects
      suffering from this disorder.

PMID- 7725292
TI  - [With Rudolf Ludwig Karl Virchow as a guide into the new community medicine].
AB  - Internationally there is an urge to vitalize the theory and practice of public
      health. A new public health emerges, characterized by: Knowledge base on
      anthropology and ecology, not on epidemiology Export of health expertise and
      commitment to other sectors: agriculture, urban planning, media, etc. Mobilizing
      and qualifying the individual as well as the local community to invest in
      personal and environmental health Focus on public health threats deriving from
      political and economic power structures. The new public health needs the old
      virtues of the pioneers of social medicine, in this article represented by
      Virchow (1821-1902): One half of the brain in biomedicine, one in social medicine
      Courage to confront the Establishment Respect for the people and a dedication to
      democratize medicine A basic instinct for social justice.

PMID- 7725295
TI  - [Quality assurance of emergency medical work].
AB  - Patients attending a casualty department often have diseases or injuries needing
      urgent medical attention. Early and correct diagnosis and treatment may be of
      major importance for the medical outcome. The continuity of staff is often low,
      with many doctors and nurses working part time. This may represent a threat to
      the quality of the medical work. Quality assurance at a casualty department
      through good training, introduction of written rules, a good flow of information
      to the staff and local licensing of doctors are factors which can assure that the
      quality of the medical service remains the best. This paper presents the work
      done at The Tromso Municipal Casualty Department to assure the quality of the
      medical service to the population.

PMID- 7725294
TI  - [What impact do social inequalities have on health status in Norway?].
AB  - OBJECTIVE: To examine the joint effects of social class, education and income on
      self-reported ill health. SETTING: A nationwide representative sample of employed
      adult Norwegians. MATERIAL: 2,134 employed Norwegians aged 20-64 years derived
      from the 1991 Survey of Level of Living. Three measures of ill health were
      studied: Long-standing somatic illness, reduced work potential because of long
      standing somatic illness, and mental health. METHODS: The relationships between
      the health outcomes and the socioeconomic indicators were modelled by means of
      multiple logistic regression. CONCLUSION: Among the selected socioeconomic
      indicators, occupational class appeared to be the most important predictor of ill
      health.

PMID- 7725293
TI  - [The conceptual values of community medicine].
AB  - The original basis of community-related medicine, hygiene, has academic
      traditions reaching back to early in the last century. The newer "free", "social
      medicine", burst forth after World War II. In the recent years, many new branches
      have arisen from these main trunks, e.g. public health, community medicine,
      epidemiology, occupational medicine, environmental medicine, health promotion
      etc. The new branches are frequently given designations that lead to false ideas
      of consistent conceptual structures that do not exist, and only contribute to
      considerable professional confusion. The author considers conceptual
      clarification to be urgent. A limited number of simple, understandable and
      logically developed main designations and classifications are needed.
      Scandinavian classification principles should be harmonized with common
      international concepts.

PMID- 7725296
TI  - [What should be done about social inequality in health? A discussion of three
      different health perspectives].

PMID- 7725297
TI  - [Intermittent claudication and beta blockaders. An unfortunate combination?].

PMID- 7725298
TI  - [Grants--length of employment and duty to work].

PMID- 7725299
TI  - [Utilization of specialists' fees during emergency service].

PMID- 7725300
TI  - [Production management on dairy farms: the road to the future].
AB  - In this paper the developments in the field of bovine herd health and production
      management are illustrated. The current use of herd health and production
      management methods in veterinary practices are illustrated, and a uniform concept
      for execution of herd health and production management programs is given. The
      expected future developments and the critical points in these developments are
      discussed. The changing role of the veterinarian in bovine practice with the
      application of herd health is outlined.

PMID- 7725303
TI  - [Computer program 'Dekt Perfekt'].

PMID- 7725302
TI  - [Pathogenic studies of Escherichia coli mastitis].
AB  - In this paper research about the pathogenesis of Escherichia coli mastitis,
      executed by the Department of Herd Health and Reproduction, is reviewed. The use
      of experimental infection models to study the systemic clinical symptoms of an
      Escherichia coli mastitis and the effect of anti-inflammatory drugs on this
      symptoms are described. Additionally, correlations between pre-infection in vitro
      leucocyte function tests and the severity of an Escherichia coli infection are
      discussed. Finally, some future developments and their possible applications are
      revealed.

PMID- 7725304
TI  - [Professor Brand's viewpoint--'The veterinarian has to come around!'. Interview
      by Sophie Deleu].

PMID- 7725301
TI  - [Subclinical and clinical mastitis on dairy farms in The Netherlands:
      epidemiological developments].
AB  - In this review a number of the main epidemiological developments in the field of
      udder health in the Netherlands are summarized. The changes considering the bulk
      milk somatic cell count are described, as are the population dynamics of
      subclinical mastitis. Additionally, clinical mastitis caused by Escherichia coli
      and Staphylococcus aureus and their risk factors are reviewed. Finally, some
      future developments and the possible applications of these developments are
      discussed.

PMID- 7725305
TI  - Locus-specific amplification of HLA class I genes from genomic DNA: locus
      specific sequences in the first and third introns of HLA-A, -B, and -C alleles.
AB  - We have identified locus-specific sequences in the first and third introns
      flanking the polymorphic second and third exons of HLA class I genes. PCR primers
      derived from these conserved sequences produced DNA fragments of the expected
      sizes for each of the HLA-A, -B, and -C loci in the amplification of genomic DNA.
      PCR products generated using each of the locus-specific sets of primers displayed
      exquisite locus specificity, as assessed by hybridization with oligonucleotide
      probes specific for ten classical and non-classical HLA class I genes.
      Amplification with these primer sets was effective and specific for the HLA
      alleles tested under the given PCR conditions. When hybridized with
      oligonucleotides derived from shared polymorphic sequence motifs, reaction
      patterns of PCR products from each locus were precisely as expected from
      published or database sequences. Chemiluminescent signals generated from
      digoxygenin-ddUTP-labeled probes were even for all samples and as strong as those
      obtained in MHC class II typing. These locus-specific primer sets derived from
      intron sequences provide an effective means to amplify genomic DNA which will
      facilitate PCR-based HLA class I typing methods. This will also allow HLA class I
      typing to be conducted with greater precision, at lower cost, and faster than
      previously described class I typing methodologies.

PMID- 7725306
TI  - HLA class I variation in Australian aborigines: characterization of allele
      B*1521.
AB  - Traditional methods of serological typing have largely used antisera of Caucasoid
      origin, which can overlook HLA heterogeneity in non-Caucasoid populations.
      Therefore, we have used molecular techniques to evaluate potential polymorphism
      in HLA class I molecules of Aborigines from the central desert and northern coast
      of Australia. The DNA sequence of common Aboriginal HLA-A and B antigens were
      compared with serological reaction patterns which suggested new polymorphisms.
      Although serological data indicated that long and short variants of A34 may
      exist, regardless of the serological pattern, all individuals carried the A*3401
      allele. Therefore, the variation in A34 reaction pattern observed serologically
      was not attributable to primary sequence variation in the HLA A*3401 allele.
      Similarly, there was no detectable polymorphism in the sequences of selected HLA
      B alleles, even though some of these alleles showed unusual serological reaction
      patterns. However, a new allele of B15 (B*1521) was detected in two individuals
      carrying this serotype. The cells from both of these individuals showed ambiguous
      reaction patterns with monospecific B62 and B75 sera. cDNA sequencing of the HLA
      B15 gene from these cells revealed a B15 allele that differed from B*1502 by a
      single nucleotide change. This change occurred at position 272, resulting in a C
      to G substitution at residue 67 in the consensus B15 cDNA sequence. Hence, the
      Australian Aborigines as an ethnic group show very little primary sequence
      polymorphism within the class I loci, consistent with the results obtained from
      previous serological studies.

PMID- 7725307
TI  - HLA-B16 antigens: sequence of the ST-16 antigen, further definition of two B38
      subtypes and evidence for convergent evolution of B*3902.
AB  - The ST-16 antigenic specificity of the HLA-B locus is defined as a B39 variant of
      Mexican-Americans. Nucleotide sequencing of cDNA shows the ST-16 allele (B*3905)
      differs from B*39011 by a single substitution that substitutes tyrosine for
      aspartic acid at position 74 of the mature class I heavy chain. The complete
      coding region sequence for the common caucasoid allele encoding the B38 antigen
      has been determined. This B*3801 allele differs from B*3802 at two nucleotide
      substitutions within the Bw4 sequence motif. B*3801 and B*3802 may have been
      derived independently from B*39011 by conversion events with B alleles donating
      distinctive Bw4 motifs. A novel allele B*39022 derived from a Colombian Indian
      differs from the B*39021 allele of Japanese origin at two widely separated silent
      substitutions. Comparison of sequences for the known B16 alleles suggest that
      B*39021 and B*39022 were independently derived by recombination from B*39013 and
      B*39011 respectively.

PMID- 7725308
TI  - Low resolution DNA typing of the HLA-B5 cross-reactive group by nested PCR-SSP.
AB  - We have established a DNA typing system for the HLA-B5 serologically cross
      reactive group (CREG) by means of a two-step PCR amplification with nested
      sequence-specific primers (nPCR-SSP). The present study provides a low resolution
      definition of the HLA-B5 CREG, i.e. identifying polymorphism equivalent to
      serology. Two different primer combinations allow group-specific amplification of
      all HLA-B5 CREG alleles and other related HLA class I alleles from genomic DNA.
      The amplified DNA is subjected to a second amplification step using eleven nested
      primer pairs. This assay permits the detection of the HLA-B5 CREG specificities
      B35, B51, B52, B53, and B7801 in all homozygous and heterozygous combinations.
      Sensitivity and specificity as judged by a blind quality control study
      investigating a reference panel (n = 50) is 100%. Extension of this approach
      should allow rapid DNA typing of all serologically defined HLA-B specificities by
      nPCR-SSP.

PMID- 7725309
TI  - Serology versus PCR-SSP in typing for HLA-DR and HLA-DQ: a practical evaluation.
AB  - In this study, serological HLA-DR and -DQ typing results were compared to typing
      results obtained with sequence-specific primers in the polymerase chain reaction
      (PCR-SSP). HLA-DR typing was performed on a random caucasian population
      consisting of 31 patients and 73 healthy individuals. Considering HLA-DR1-10,
      differences in typing results were found in 3 out of 73 healthy individuals and 8
      out of 31 patients. When HLA-DR1-16 alleles were taken into account, differences
      in typing results were found in 11 out of 31 patients and 14 out of 73 healthy
      individuals. Typing results of PCR-SSP, different from that of serology, were all
      confirmed by sequencing-based typing of HLA-DRB1 alleles. HLA-DQ1-3 typings were
      performed on 40 individuals consisting of 17 patients and 23 healthy individuals.
      Differences in typing results were found in 5 out of 17 patients and 1 out of 23
      healthy individuals. From the results of this study it can be concluded that
      serology is a reliable technique, when restricted to identification of HLA-DR1-10
      and HLA-DQ1-3 antigens in healthy individuals. By PCR-SSP, however, reliable HLA
      DR1-16 and -DQ1-3 typings can be obtained both in patients and healthy
      individuals.

PMID- 7725310
TI  - High resolution HLA-DRB1 SSP typing for cadaveric donor transplantation.
AB  - An HLA-DRB1 typing procedure by means of sequence-specific primer (SSP)
      amplification was developed for 65 different DRB1 subtypes. Subtyping is achieved
      by the performance of two subsequent PCR assays (PCR-1 assay and PCR-2 assay)
      using a limited number of reactions. The PCR-1 assay determined low-resolution
      HLA-DRB1 typing, i.e. the serologically defined specificities DR1, 2, 3, 4, 11,
      12, 6, 7, 8, 9 and 10. The second exon of the DRB1 gene is amplified also in this
      PCR-1 assay. High-resolution subtyping for positively identified alleles was
      performed in the PCR-2 assay with the exon-2 product from PCR-1 assay as DNA
      template. PCR reactions were carried out using unpurified primers in reaction
      volumes of 20 microliters and 100 ng of chromosomal DNA. After 3 hours, the
      results of the PCR-1 assay were analyzed and subsequently subtyping results in
      the PCR-2 assay were obtained in another 1.5 hours. A total of 249 DNA samples
      was typed by this method. No false positive nor false negative results were
      obtained in DRB1 typing of 32 homozygous cell lines, 56 serologically well
      defined panel cells and 125 unrelated individuals. Segregation of the
      amplification patterns was investigated in 36 members of 7 two-generation
      families. DRB1 subtyping revealed codominant Mendelian segregation for all
      subtypes investigated. In conclusion, LR-HR-PCR-SSP typing is a fast and reliable
      typing technique for routine DNA typing purposes which gives complete DRB1
      subtyping within 4.5 h. Besides low-resolution DRB typing, also high-resolution
      DRB subtyping for prospective HLA-DR matching in cadaveric renal transplantation
      is possible by this method.

PMID- 7725311
TI  - Significance of the HLA-DQB matching in one-haplotype identical kidney transplant
      pairs and the matching analysis by the polymerase chain reaction (PCR)-
      heteroduplex--polymorphism method.
AB  - Sixty-five living related kidney transplant pairs were analyzed for matching at
      HLA class II loci by the polymerase chain reaction (PCR)--sequence specific
      oligonucleotide probe (SSOP) method. The retrospective HLA matching study
      revealed that there were many early graft loss cases despite the DQB
      compatibility, contrary to our expectation. There were 54 DRB1 one-mismatched
      cases, in which 7 of the 11 (64%) DQB zero-mismatched cases had lost their
      grafts, while the graft loss cases were only 10 of the 43 (23%) DQB one
      mismatched pairs (P value = 0.0006). The DQB matching of these cases was studied
      in detail, because the PCR-SSOP methods are based on the detection of sequence
      polymorphisms in a relatively narrow range, i.e., recognized sequences by SSOPs.
      The PCR--heteroduplex--polymorphism analysis method was developed to analyze the
      polymorphism in exon 2 of the DQB1 gene. However, all the pairs proved to be
      compatible for the DQB, demonstrating that the DQB compatibility was associated
      with a harmful influence on the graft outcome. These observations suggested that
      the DQB1 incompatibility might exert the low responsiveness to HLA haplo
      identical allogeneic transplants.

PMID- 7725312
TI  - Sequencing-based typing reveals new insight in HLA-DPA1 polymorphism.
AB  - An HLA-DPA1 sequencing-based typing (SBT) system has been developed to identify
      DPA1 alleles. Up to now eight DPA1 alleles have been defined. Six can be
      discriminated based upon exon 2 polymorphism. The three subtypes of DPA1*01:
      DPA1*0101, DPA1*0102 and DPA1*0103, have identical exon 2 sequences but show
      differences in exon 4. Exon 4 sequences were known for only the three DPA1*01
      subtypes and for DPA1*0201. We now present additional sequence information for
      exon 4 and the unknown segments at the 3' end of exon 2. Additionally with the
      use of this sequencing technique it is also possible to identify previously
      unidentified polymorphism. We have studied the exon 2 and exon 4 polymorphism of
      DPA1 in 40 samples which include all known DPA1 alleles. A new allele, DPA1*01
      new, was identified which differs by one nucleotide in exon 2 from DPA1*0103,
      resulting in an aspartic acid at codon 28. The DPA1*01 subtypes DPA1*0101 and
      DPA1*0102 could not be confirmed in samples which previously were used to define
      these subtypes, and consequently they do not exist. The exon 4 sequence of
      DPA1*0201 is corrected based on sequence data of DAUDI, the cell line in which
      DPA1*0202 was originally defined. The exon 4 regions of the remaining four
      alleles were resolved: the exon 4 regions of the alleles DPA1*02021 and
      DPA1*02022 were found to be identical to the--corrected--DPA1*0201 whereas the
      exon 4 region of DPA1*0301 differs by one nucleotide compared to DPA1*0103. The
      DPA1*0401 exon 4 region differs by one nucleotide compared to the corrected
      DPA1*0201.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725315
TI  - Molecular characterization of a novel HLA-A33 allele (A*3303).

PMID- 7725313
TI  - HLA class II gene polymorphism in Tunisians.
AB  - The polymorphism of HLA class II genes (HLA-DRB, DQB, DPB) was investigated in
      101 Tunisians using polymerase chain reaction. (PCR) amplification and reverse
      dot blot (RDB) hybridization. Allele and haplotype frequencies, as well as DRB1
      DQB1 linkage disequilibria, were calculated. A total of 26 DRB1 alleles were
      detected and the most prevalent variant was DRB1*0301 with an allelic frequency
      at 21.87%. In the DR1 group, DRB1*0102 was most frequent than DRB1*0101. In the
      DR4 group, DRB1*0403 was the most common allele and was associated with
      DQB1*0402. Interestingly this DRB1-DQB1 association has not been observed in
      other populations. With regard to the DR8 group, DRB1*0804 was the unique variant
      detected, whereas with the DR13 specificity, the most common variant was
      DRB1*1303 in Algerians also. Although the DQB1 polymorphism analysis showed an
      allelic distribution very close to that observed in caucasoids, many DRB1-DQB1
      associations which have not been reported in studies of other populations, were
      described. Finally at the DPB1 locus DPB1*1701 and *1301 allele frequencies
      distinguish clearly this Tunisian sample from a French caucasoid panel of 83
      subjects. In conclusion, a specific distribution of HLA components in terms of
      gene and haplotype frequencies characterizises this Tunisian population. This
      specific pattern may reflect the great ethnic diversity of this community. All
      these informations may be helpful in the future for HLA and disease association
      studies.

PMID- 7725314
TI  - Genotyping of the granulocyte-specific NA antigens from small quantities of blood
      or serum.
AB  - To avoid the well-known shortcomings of phenotyping granulocytes for the NA
      antigens using NA-specific human sera, a DNA-based method to determine the NA
      genotype was developed. Genomic DNA was isolated from blood cells or serum,
      amplified by polymerase chain reaction (PCR), immobilized on nylon membrane and
      genotyped using digoxigenin-labeled, sequence-specific oligonucleotides (SSO).
      The genotyping results of whole blood samples from 54 and of serum from 20
      individuals correlated perfectly with our phenotyping using the antigen capture
      assay MAIGA. In three cases with the phenotype "NA-null" no hybridization of the
      NA-specific oligonucleotides occurred. These data show that SSO is a reliable
      method for NA genotyping especially if only small volumes of blood or even only
      serum probes are available.

PMID- 7725316
TI  - Caucasian patients with rheumatoid factor-positive RA.

PMID- 7725317
TI  - Isolation of a toxin from Centruroides infamatus infamatus Koch scorpion venom
      that modifies Na+ permeability on chick dorsal root ganglion cells.
AB  - A novel toxin was isolated and characterized from the venom of the Mexican
      scorpion Centruroides infamatus infamatus. It has an apparent mol. wt of 7600,
      compatible with the presence of 66 amino acid residues per molecule. The N
      terminal amino acid sequence was determined (up to residue 48) and showed
      approximately 95% similarity with toxins from other Mexican scorpions of the gnus
      Centruroides. Experiments conducted with chick dorsal root ganglion cells showed
      that toxin 1 is a Na+ channel effector, causing a decrease in the peak Na+
      permeability, similar to decreases observed for typical beta-scorpion toxins.

PMID- 7725318
TI  - Use of a colorimetric protein phosphatase inhibition assay and enzyme linked
      immunosorbent assay for the study of microcystins and nodularins.
AB  - Microcystins and nodularins are cyclic peptide hepatotoxins and tumor promoters
      produced by several genera of cyanobacteria. Using a rabbit anti-microcystin-LR
      polyclonal antibody preparation, the cross-reactivity with 18 microcystin and
      nodularin variants was tested. A hydrophobic amino acid, 3-amino-9-methoxy-10
      phenyl-2,6,8-trimethyl-deca-4(E),6(E)-dienoic acid (Adda), which has the (E) form
      at the C-6 double bond in both microcystin and nodularin, was found essential for
      these toxins to express antibody specificity. Modification of -COOH in glutamic
      acid of microcystin and nodularin did not alter their antigenicity. Antibody
      cross-reactivity of these toxins was compared with their ability to inhibit
      protein phosphatase type 1 (PP1). Detection of PP1 inhibition was done by
      measuring the inhibition effect of the toxins on p-nitrophenol phosphate activity
      toward PP1. PP1 was obtained as recombinant PP1 expressed in E. coli. The
      inhibition effect of five microcystins and two nodularins on recombinant PP1
      activity toward p-nitrophenol phospate was measured in a microwell plate reader.
      The concentration of microcystin-LR causing 50% inhibition of recombinant PP1
      activity (IC50) was about 0.3 nM, while that of two modified microcystins had a
      significantly higher IC50. Microcystin-LR and nodularin with the (z) form of Adda
      at the C-6 double bond or having the monoester of glutamic acid did not inhibit
      PP1. These three toxins were also nontoxic in the mouse bioassay. These results
      show the importance of Adda and glutamic acid in toxicity of these cyclic
      peptides and that PP1 inhibition is related to the toxins' mechanism of action.

PMID- 7725319
TI  - Purification and characterization of a coagulant enzyme, okinaxobin II, from
      Trimeresurus okinavensis (himehabu snake) venom which release fibrinopeptides A
      and B.
AB  - A coagulant enzyme, okinaxobin I, which was purified from Trimeresurus okinavenis
      (himehabu snake) venom, released specifically fibrinopeptide B from fibrinogen to
      form fibrin clots. In the present study, its isozyme denoted as okinaxobin II has
      been purified to homogeneity from the same venom by chromatographies on Sephadex
      G-100, CM-Toyopearl 650M, and FPLC Mono-Q columns. Differently from okinaxobin I,
      okinaxobin II specifically cleaved fibrinopeptides A and B from fibrinogen
      similarly as found for alpha-thrombin. The enzyme acted on fibrinogen with
      specific activity of 42 NIH units/mg at optimum pH of 8.0. Okinaxobin II was a
      monomeric glycoprotein with a mol. wt of 37,500 on SDS-PAGE, which was reduced to
      29,500 after treatment with N-glycanase. Okinaxobin II was much more basic (pI =
      8.1) than okinaxobin I (pI = 5.4). The N-terminal sequence was highly similar to
      those of okinaxobin I and some other snake venom coagulant enzymes such as
      flavoxobin (Trimeresurus flavoviridis), batroxobin (Bothrops atrox and Bothrops
      moojeni), and catroxobin (Crotalus atrox). Okinaxobin II hydrolyzed tosyl-L
      arginine methyl ester and benzoyl-L-arginine p-nitroanilide. The esterase
      activity was strongly inhibited by diisopropylfluorophosphate and to a lesser
      extent by tosyl-L-lysine chloromethyl ketone, indicating that the enzyme is a
      serine protease like alpha-thrombin. In terms of amino acid composition,
      okinaxobin II was similar to okinaxobin I and dissimilar to alpha-thrombin.

PMID- 7725320
TI  - Purification and characterization of fibrolase isoforms from venom of individual
      southern copperhead (Agkistrodon contortrix Contortrix) snakes.
AB  - Fibrolase, a zinc metalloproteinase possessing direct-acting fibrinolytic
      activity, has been previously purified from southern copperhead (Agkistrodon
      contortrix contortix) snake venom. We recently reported that a pool of southern
      copperhead venom from different geographical locations possesses two isoforms of
      fibrolase (fib1 and fib2) [Loayza, S. L. et al. (1994) J. Chromat. B, in press].
      We now report that venom from individual southern copperhead snakes contains the
      two isoforms which can be separated by a three-step high performance liquid
      chromatography (HPLC) procedure consisting of hydrophobic interaction
      chromatography, hydroxylapatite chromatography and weak cation exchange
      chromatography. Utilizing mass spectrometry we determined that fib1 has a
      molecular mass of 22,879 atomic mass units (amu) compared to 22,753 amu for fib2.
      These results support earlier observations during amino acid sequence analysis
      that a truncated version of the enzyme is produced which is missing the amino
      terminal amino acid (< Glu-Arg-Phe-Pro vs. the intact enzyme < Glu-Gln-Arg-Phe
      Pro, where < Glu is cyclized glutamine). The truncated version of fibrolase
      (fib2) has full fibrinolytic activity compared to fib1. EC50 values
      (concentration of enzyme required to degrade 50% of fibrin in a micro-fibrin
      plate assay) are 6.4 (+/- 1.0) microM and 5.2 (+/- 0.8) microM for fib 1 and
      fib2, respectively. Therefore, loss of the amino-terminal amino acid does not
      appear to influence enzymatic activity. We conclude that the two isoforms of
      fibrolase arise from variations in the molecular processing of the enzyme by the
      snake venom gland rather than being caused by the pooling of southern copperhead
      venoms from different geographical locations.

PMID- 7725321
TI  - Poisoning by the red alga 'ogonori' (Gracilaria verrucosa) on the Nojima Coast,
      Yokohama, Kanagawa Prefecture, Japan.
AB  - A food poisoning case due to the ingestion of 'ogonori', an edible red alga,
      occurred at Yokohama, Kanagawa Prefecture, Japan, in late October 1993, resulting
      in two victims, including one death (female). No causative agent present in the
      ogonori was found from a routine bioassay for marine toxins. From the production
      of increased amounts of prostaglandins (PGs), mainly PGE2, by the alga on
      stimulation by cutting or soaking in fresh water, and further increase of PGE2 by
      addition of arachidonic acid, it appeared that an enzyme, probably fatty acid
      cyclooxygenase, in the ogonori and the body of the victim, was acting on the
      highly unsaturated fatty acids in the oil of the ingested seafood and in the
      blood hemorrhaged from the stomach of the victim. This resulted in the production
      of over 30 mg of PGE2 and small amounts of other PGs in a comparatively short
      time. With this dosage the victim suffered from nausea, vomiting, and
      hypotension, and died of hypotensive shock. PGE2 seems to work more selectively
      on females. This type of poisoning is very unusual, and differs from the more
      familiar forms of poisoning occurring after ingestion of marine organisms.

PMID- 7725322
TI  - Severe ciguatera poisoning in Madagascar: a case report.
AB  - In a single outbreak on the East coast of Madagascar, more than 500 people, 98 of
      whom died, were poisoned by the flesh of a shark, Carcharhinus amboinensis. From
      clinical symptoms it can be concluded that this poisoning is due to ciguatera
      toxins. It is the first case of a severe outbreak caused by a shark, and it is
      the first case with a mortality rate of 20%.

PMID- 7725323
TI  - Some enzymic activities of two Australian ant venoms: a jumper ant Myrmecia
      pilosula and a bulldog ant Myrmecia pyriformis.
AB  - Venoms from two related Australian ants, a jumper ant (Myrmecia pilosula) and a
      bulldog ant (Myrmecia pyriformis), were quantitatively analysed for the following
      enzymic activities: phospholipase A2, phospholipase B, phospholipase C,
      hyaluronidase, esterase, acid phosphatase, alkaline phosphatase and
      phosphodiesterase. Both venoms contained phospholipase A2, phospholipase B,
      hyaluronidase, acid phosphatase and alkaline phosphatase activities. Myrmecia
      pyriformis venom had significantly greater phospholipase B, acid phosphatase and
      alkaline phosphatase activities than Myrmecia pilosula venom. No detectable
      quantities of phospholipase C, esterase or phosphodiesterase activities were
      found in either venom.

PMID- 7725324
TI  - Isolation, purification and partial characterization of viper venom inhibiting
      factor from the root extract of the Indian medicinal plant sarsaparilla
      (Hemidesmus indicus R. Br.).
AB  - An organic acid, isolated and purified from the root extract of an Indian
      medicinal plant sarsaparilla Hemidesmus indicus R. Br, possessed viper venom
      inhibitory activity. The compound (designated HI-RVIF) was isolated by solvent
      extraction, silica gel column chromatography and thin layer chromatography, and
      was homogeneous in nature. The white needle-shaped crystals were soluble in
      water, methanol and chloroform and had a melting point of 155-158 degrees C and
      lambda max 260 nm. Spectral analysis confirmed the presence of a benzene ring,
      methoxy group, and hydroxyl group; the mol. wt of the compound was 168. HI-RVIF
      significantly antagonized viper venom-induced lethal, haemorrhagic, coagulant and
      anticoagulant activity in experimental rodents.

PMID- 7725325
TI  - The effects of five phospholipases A2 from the venom of king brown snake,
      Pseudechis australis, on nerve and muscle.
AB  - The effects on vertebrate neuromuscular function of five homologous
      phospholipases A2 (PLA2) (Pa-3, Pa-8, Pa-9C, Pa-10F and Pa-12B) from the venom of
      the Australian king brown snake, Pseudechis australis, were determined. These
      isoenzymes (0.2-1.6 microM) reduced, with different potencies, responses of chick
      biventer cervicis preparations to nerve stimulation and to exogenously applied
      acetylcholine, carbachol and KCl in a time- and concentration-dependent way but
      with different potencies. They also blocked twitches of mouse hemidiaphragm
      preparations evoked by nerve and by direct muscle stimulation. Pa-8 was the most
      active and Pa-9C was the least potent. There was a strong correlation between the
      enzymatic activity and the effect of toxins on the responses of mouse
      hemidiaphragm to direct muscle stimulation, but weak correlation between the
      effects on indirect responses and enzymatic activity. Intracellular recording
      from endplate regions of mouse triangularis sterni nerve-muscle preparations
      showed that Pa-10F and Pa-12B at 0.2 microM significantly reduced quantal content
      after 10 min. Pa-8 (0.2 microM) reduced the amplitude of endplate potentials by
      about 25% and abolished miniature endplate potentials within 15 min. Pa-3 (0.2
      microM) and Pa-9C (0.8 microM) also significantly reduced quantal content by
      about 30% of control after 30 min. Among these toxins, Pa-3 and Pa-8 at 0.2
      microM depolarised mouse muscle fibres after 30 min. Extracellular recording of
      action potentials at motor nerve terminals of mouse triangularis sterni
      preparations indicated that these isoenzymes reduced the waveforms associated
      with both Na+ and K+ conductances. Since no facilitatory effect on the release
      process has been observed, the apparent blockade of K+ conductance by some of
      these toxins may not be a selective action on K+ channels, but may be secondary
      to membrane depolarisation. An in vivo study with Pa-8 and Pa-10F demonstrated
      myotoxic effects. Light microscopic examination showed a degeneration of mouse
      and rat skeletal muscle fibres caused by Pa-8 and Pa-10F. For the in vivo study,
      rats received 80 micrograms/kg of the toxins s.c. and mice were injected i.m.
      with the toxins (40 micrograms/kg). Myotoxicity appears to be the predominant
      effect of these five toxins.

PMID- 7725326
TI  - Gonyautoxin-3 as a minor toxin in the gastropod Niotha clathrata in Taiwan.
AB  - Paralytic toxicity was detected in the gastropod mollusc Niotha clathrata
      collected from South Taiwan in April and November 1993. Each seasonal toxin was
      partially purified from toxic specimens of N. clathrata by ultrafiltration using
      a membrane (Diaflo YM-2), followed by chromatography on a column (Bio-Gel P-2).
      Two toxin fractions (I and II) were then obtained for each seasonal shell toxin.
      The ratio of fraction I to fraction II for each seasonal shell toxin was about
      4:1 according to tetrodotoxin bioassay. Based on analyses by TLC,
      electrophoresis, and HPLC, fraction I toxin contained tetrodotoxin and its
      derivative anhydrotetrodotoxin, and fraction II toxin contained gonyautoxin-3 for
      each seasonal shell toxin.

PMID- 7725327
TI  - Clostridium sordellii cytotoxin induces phosphorylation of an 80,000 mol. wt
      protein in McCoy cultured cells.
AB  - The cytotoxins from Clostridium difficile (toxin B) and Clostridium sordellii
      (toxin L) induce rounding of cultured cells. The cellular effects induced by
      these two cytotoxins are clearly distinct, suggesting that both toxins use a
      similar, but not identical mechanism for cell intoxication. We have employed the
      technique of two-dimensional PAGE for the separation of 32P-labelled cell lysates
      of McCoy cultured cells to investigate changes in the phosphorylation status of
      cellular proteins after treatment with toxin B and with toxin L. The two
      dimensional electrophoresis patterns suggest the implication of an 80,000 mol. wt
      cellular protein (named pp80c) in the cytopathic action of the cytotoxin from C.
      sordellii. This protein shows immunoreactivity with non-muscle caldesmon. Toxin
      B, however, does not affect the phosphorylation of pp80c, but alters the
      phosphorylation of another cellular protein, pp77, indicating another mechanism
      for cell intoxication. In addition, our experiments suggest that the mechanism of
      action of okadaic acid, a phosphatase inhibitor which causes cell rounding
      similar to that induced by C. sordellii, and these two cytotoxins are different.

PMID- 7725328
TI  - Comparative study of the stability of saxitoxin and neosaxitoxin in acidic
      solutions and lyophilized samples.
AB  - Paralytic shellfish poison (PSP) has historically been a problem for the
      shellfish industry. In order to prevent the marketing of contaminated seafood
      products, governments have implemented monitoring programs where standards of
      toxins are necessary. The stability of these standard toxins is very important.
      In this paper we analysed the stability of saxitoxin (STX) and neosaxitoxin in
      acidic solution and lyophilized samples. Individual toxins were determined in
      each sample using a high-performance liquid chromatographic procedure employing
      post-column oxidation of the toxins to form fluorescent derivatives. Our results
      demonstrate that STX is very stable in solution samples and could be adopted as a
      reference standard. This toxin can be kept in dilute acidic solutions for 18
      months without loss of potency. However, neosaxitoxin is unstable, possibly due
      to transformation to other toxins.

PMID- 7725330
TI  - Action of Calloselasma rhodostoma (Malayan pit viper) venom on human blood
      coagulation and fibrinolysis using computerized thromboelastography (CTEG).
AB  - The effects of Malayan pit viper (Calloselasma rhodostoma) venom on human blood
      coagulation and fibrinolysis were studied in vitro using computerized
      thromboelastography. At low concentrations the venom had a coagulant effect shown
      by faster onset of the coagulation process (shortened SP and R), faster progress
      of the clot (increased angle and shortened K), and increased coagulation (TEG)
      index. The maximum amplitude (MA) was not affected, suggesting that the venom had
      no apparent effect on platelet function; and clot lysis was similar to that in
      the controls, suggesting that there was no primary fibrinolytic activity. At
      higher concentrations the venom had anticoagulant effects, SP and R were
      progressively shortened, but there was poor/no progress in the clot formed,
      evident from prolonged or absent K, diminished MA and reduced angle. These
      results show that C. rhodostoma venom has both coagulant and anticoagulant
      actions. The coagulant action may be due to Factor X activator predominance at
      low concentrations, while the anticoagulant action could be due to ancrod action.
      TEG is able to demonstrate the dual effect of this venom, previously described as
      a paradox, and may be a useful tool in the diagnosis and monitoring of
      envenomation patients.

PMID- 7725329
TI  - Androctonus crassicauda (Olivier), a dangerous and unduly neglected scorpion--I.
      Pharmacological and clinical studies.
AB  - Androctonus crassicauda venom has an i.v. LD50 in mice of 0.32 +/- 0.02 mg/kg,
      which makes the scorpion among the most toxic species in the world. Fifty-one non
      fatal and one fatal cases of scorpion sting were presented. Pain and tenderness
      were very common following the sting. Generalized erythema occurred in 20-25% of
      all infants and children below the age of 5 years. Severe CNS manifestations
      including seizures, unconsciousness and marked irritability occurred mainly in
      infants and young children, while hypertension occurred in the majority of
      victims below the age of 11 years. Two pregnant victims were treated with
      antivenom with no bad consequences on mothers or foetuses. The fatal case
      described was inadequately treated with antivenom and presented a rare situation
      of intracranial coagulation in the basal cisterns or low in the cranial
      subarachnoid space. The victim developed moderate hydrocephalus of the
      communicating type with clear ventricular CSF and strongly xanthocromic fluid
      from lumbar puncture. The effects of A. crassicauda venom on isolated hearts,
      atria and anaesthetized rat blood pressure appeared to be mediated largely
      through stimulation of the autonomic nervous system with predominance of
      sympathetic stimulation and release of tissue catecholamines. Electrocardiograms
      recorded simultaneously with blood pressure changes showed evidence of ectopic
      foci during the hypertensive phase and ischaemia, inferior wall infarction and
      different degrees of heart block during the late hypotensive phase. Androctonus
      crassicauda venom was unique in following a three-compartment open model
      comprising a central compartment 'blood', a rapidly equilibrating 'shallow'
      tissue compartment and a slowly equilibrating 'deep' tissue compartment. The
      overall elimination half-life, t1/2 beta, was 24 hr, indicating that the venom
      has the slowest elimination among all known scorpion venoms. The long stay of the
      venom in the body might explain the increased risk of toxicity and the good
      potential for treatment with serotherapy even hours after the sting.

PMID- 7725332
TI  - ELISA for the detection of toxic antigens in experimental and clinical envenoming
      by Tityus serrulatus scorpion venom.
AB  - An ELISA was developed for identification of circulating toxic antigens from
      Tityus serrulatus scorpion venom. The toxic fraction from the scorpion venom was
      purified by Sephadex G-50 chromatography and immunoaffinity techniques were used
      for identifying antibodies that reacted with this fraction. These antibodies were
      used to develop a sandwich-type ELISA. The specificity of the assay was
      demonstrated by its capacity for identifying mice that were experimentally
      inoculated with T. serrulatus venom from those inoculated with Phoneutria
      nigriventer spider venom, Apis mellifera bee venom and Bothrops atrox, Crotalus
      durissus terrificus, Lachesis muta muta and Micrurus frontalis snake venoms.
      Measurable absorbance signals were obtained with 0.1 ng of venom per assay. The
      ELISA also detected antigens in the sera of patients systemically envenomed by T.
      serrulatus. Therefore, this ELISA could be a valuable tool for clinicians and
      epidemiologists, owing to its sensitivity and specificity.

PMID- 7725331
TI  - Effects of Tityus serrulatus crude venom on the GABAergic and dopaminergic
      systems of the rat brain.
AB  - This study was designed to investigate the effect of T. serrulatus scorpion venom
      on dopamine (DA) and gamma amino butyric acid (GABA) concentrations in different
      regions of the brain. The ratio of homovanillic acid (HVA) to DA, and the
      glutamic acid decarboxylase (GAD) activity were determined following intravenous
      or intracerebral venom injections. The increase in the HVA/DA ratio in the
      striatum after i.v. or intrastriatal injection could indicate an increase in DA
      turnover. One hour after i.v. injection of the venom GAD activity was shown to be
      decreased in the striatum and hypothalamus. After 24 hr GAD activity increased in
      the striatum and decreased in the hypothalamus and brain stem. These results
      could indicate different effects of the venom on the GABA system in different
      areas of the brain. After intrastriatal injection of the scorpion venom, the
      animals showed stereotyped behavior and rotation activity. Following
      intrahippocampal injection, myoclonus and orofacial automatisms, which constitute
      pro-convulsive signals, were observed. These behavioral alterations could be, at
      least in part, related to the GABA and dopamine alterations caused by the venom,
      since stereotypy, circling behavior and convulsions are dependent on dopamine
      and/or GABA.

PMID- 7725333
TI  - Experimental evaluation of ovine antisera to Thai cobra (Naja kaouthia) venom and
      its alpha-neurotoxin.
AB  - Conventional treatment of Naja kaouthia (Thai cobra) envenoming requires large
      volumes (up to 600 ml) of equine antivenom, which results in a high incidence of
      serum reactions. The inefficiency of the antivenom is assumed to be related to
      the high percentage (approx. 20%) of alpha-neurotoxin, a relatively weak and
      highly toxic immunogen, present in the native venom. First, antibodies to N.
      kaouthia venom were raised in sheep, which protected mice against challenge with
      whole venom. Second, ovine antibodies to the purified neurotoxin and to three
      different neurotoxin conjugates were developed and their neutralising abilities
      against either whole venom or neurotoxin were compared using murine ED50 tests.
      High titre antibodies, assessed by enzyme immunoassay and Western blot, were
      obtained from all four neurotoxin immunisation regimens. Neurotoxin conjugated to
      rabbit anti-sheep IgG produced the highest titres against both neurotoxin and
      whole venom. This antiserum provided protection against neurotoxin challenge but
      failed to protect against whole venom. Furthermore, the addition of neurotoxin
      antibodies to whole venom antiserum did not enhance the neutralisation efficacy
      of the latter. These findings raise the possibility that in mice other toxins
      apart from the neurotoxin may significantly contribute to the lethal effect of N.
      kaouthia venom.

PMID- 7725334
TI  - Development of alpha-neurotoxin antibodies in patients envenomed by the
      monocellate Thai cobra (Naja kaouthia).
AB  - Serum samples from 50 patients envenomed by the Thai cobra (Naja kaouthia) were
      tested by enzyme immune assay for the presence of antibodies against the
      principal neurotoxin. Samples were taken between 1 month and 19 years after the
      bite. Only 16% (8/50) of the samples were positive for antibodies against
      neurotoxin, while 76% (38/50) were positive for antibodies against whole venom.
      There was no clear correlation between the presence of antibodies against
      neurotoxin and clinical features.

PMID- 7725335
TI  - Isolation and structure determination of a new marine neurotoxin from the New
      Zealand shellfish, Austrovenus stutchburyi.
AB  - A new marine neurotoxin was isolated from a water extract of the New Zealand
      shellfish, Austrovenus stutchburyi, by chromatography on columns of Sephadex G-15
      and LH-20, followed by reverse-phase HPLC. It was identified as (4
      methoxycarbonylbutyl)trimethyl-ammonium chloride, and this was confirmed by
      synthesis.

PMID- 7725336
TI  - Abnormal coronary perfusion in experimental scorpion envenomation.
AB  - Perfusion defects and left ventricular dilation after experimental scorpion
      envenomation were evaluated in five dogs. Left Left ventricular dilation was
      observed in three dogs and right ventricular dilation in one other, in scans
      immediately after envenomation. Perfusion defects were inferred from scans in
      four dogs. The data are strongly suggestive of coronary hypoperfusion, and the
      mechanics of abnormal coronary flow after scorpion envenomation are discussed.

PMID- 7725338
TI  - A genomic region encoding stonefish (Synanceja horrida) stonustoxin beta-subunit
      contains an intron.
AB  - The polymerase chain reaction (PCR) has been used to amplify a 1899 base pair
      fragment from stonefish genomic DNA. A comparison of the translated nucleotide
      sequence of this product with the separately determined N-terminal amino acid
      sequence of the beta-subunit reveals the presence of a 416 bp intron at Gly 18.
      The nucleotide sequence following this intron encodes 476 amino acids whose
      sequence showed no homology to other known toxins. This region, however,
      contained amino acid sequences identical to internal peptide sequences determined
      separately from the toxin's beta-subunit.

PMID- 7725339
TI  - Effect of various Viperidae and Crotalidae snake venoms on endothelial cells in
      vitro.
AB  - The effect of various crotalid and viperid venoms at 10, 50 and 100 micrograms/ml
      was examined on bovine and murine endothelial cells in vitro. The venoms caused
      the cells to lose their processes, leading to the appearance of spaces which were
      gradually enlarged between clusters of cells. The cells became round and finally
      detached from the substrate. This effect was more pronounced on bovine normal
      cells than on murine transformed cells. Most of the venoms did not affect the
      viability of the cells even after 24 hr of incubation, as determined by the
      trypan blue dye exclusion procedure. Moreover, after the cells were washed from
      the venoms and transferred into fresh medium, they regained their original
      morphology after spreading on the substrate and they then proliferated normally.
      This reversible effect shows that most of the crotalid and viperid venoms
      examined were not directly cytotoxic to the endothelial cells at the
      concentrations tested.

PMID- 7725337
TI  - Expression of glutathione S-transferase-cardiotoxin fusion protein in Escherichia
      coli.
AB  - We report here the construction of cardiotoxin V gene, from cobra snake venom
      (Naja naja atra), by chemically synthesized oligonucleotides and its expression
      as a glutathione S-transferase-cardiotoxin fusion protein in the inclusion bodies
      of Escherichia coli. The expression of cardiotoxin fusion protein in protein with
      a yield of about 35 mg/liter culture was confirmed by highly specific anti
      peptide antibodies generated against the unique amino acid residues located at
      the tip of loop II of cardiotoxin V. Since the fusion protein can be easily
      treated by CNBr to free the toxin moiety, as revealed by immunoblotting of the
      cleaved protein, the results provide an avenue for future structural and
      functional studies of cardiotoxin molecules.

PMID- 7725340
TI  - Bibliography of toxinology.

PMID- 7725341
TI  - Acute regulation of hepatic glutathione S-transferase by insulin and glucagon.
AB  - The intravenous administration of insulin plus glucose in anesthetized rats
      caused, within 30 min, an increase of about 56% in hepatic cytosolic glutathione
      S-transferase (GST) activity, but it did not affect the microsomal enzyme. The
      injection of glucagon resulted, at the same time, in a 43% drop in the hepatic
      cytosolic GST, without affecting the microsomal GST. The insulin-dependent
      increase in cytosolic GST activity was abolished by the pretreatment of the
      animals with an inhibitor of protein synthesis (cycloheximide). A kinetic
      analysis revealed a non-competitive inhibition caused by glucagon upon the
      cytosolic enzyme. In addition, the presence of insulin did not interfere with the
      effectiveness of glucagon, and vice versa. We propose that: (1) the effect of
      insulin on hepatic cytosolic GST activity requires protein synthesis; (2)
      glucagon produces an inhibition of hepatic cytosolic GST, which could be mediated
      by cytosolic effectors such as adenosine 3'-5'-cyclic monophosphate (cAMP); (3)
      the effects of glucagon and insulin were not mutually exclusive; (4) hepatic
      microsomal GST is regulated by different mechanism(s).

PMID- 7725342
TI  - Chromosomal damage in workers occupationally exposed to chronic low level
      ionizing radiation.
AB  - Chromosomal aberrations were evaluated in cultures of peripheral lymphocytes from
      subjects working in diagnostic X-ray and nuclear medicine areas, exposed to
      electromagnetic ionizing radiation and particulate ionizing emissions,
      respectively. A 4-fold increase in the level of chromosomal aberrations was found
      between the exposed and control groups without qualitative or quantitative
      cytogenetic differences between X-rays and nuclear medicine-exposed workers.
      Results are discussed in view of the early damage detection from chronic
      exposures particularly related to biological controls, hygienic improvements and
      overwork in a developing country.

PMID- 7725343
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) distribution and cytochrome P4501A
      induction in young adult and senescent male mice.
AB  - While the developmental toxicology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      and its congeners has received considerable attention, the impact of advanced age
      on the biochemical effects and the pharmacokinetics of dioxins remains largely
      undetermined. In the present investigation, TCDD tissue distribution and
      cytochrome P4501A (CYP1A) induction were characterized in male C57BL/6N mice aged
      10 weeks and 28 months at 7 days after administration of single oral [3H]TCDD
      doses ranging from 0.015 to 15 microgram/kg body wt. Determinations of hepatic
      marker enzyme activities for CYP1A1 (ethoxyresorufin O-deethylation, EROD) and
      1A2 (acetanilide-4-hydroxylation, ACOH) indicated that the dose response curves
      for EROD induction by TCDD were nearly identical for the 2 age groups, but the
      ACOH induction response was greater in old mice. After receiving the 15
      micrograms/kg dose, an increase (approximately 35%) in relative liver weight was
      observed 7 days after dosing in the 10-week mice, but not in the aged mice, and
      the hepatic concentration of TCDD was approximately 25% greater in young than old
      mice. No age difference was found in hepatic nuclear concentrations of TCDD. A
      dose-dependent increase in liver:fat tissue concentration ratios was noted at
      both ages, and adipose tissue and blood concentrations of TCDD did not vary
      significantly with age. In old mice however, TCDD concentrations in skin, kidney
      and muscle were all approximately twice those of young mice at the 15
      micrograms/kg dose. These results suggest that advanced age may have differential
      effects on Ah receptor-mediated enzyme induction, while increased TCDD
      concentrations in certain tissues may have toxicological implications for older
      animals.

PMID- 7725344
TI  - Gentamicin-induced kidney damage and lipid peroxidation in rats.
AB  - Although it has been reported that injections of gentamicin induces lipid
      peroxidation in rat renal cortex (Ramsammy et al. (1985) Biochem. Pharmacol. 34,
      3895-3900), our results showed no modification of thiobarbituric-reagent
      substances (TBARS) or in analysis of the polyunsaturated fatty acid profile.
      Moreover, endogenous vitamin E and glutathione were not consumed. In in vitro
      systems, gentamicin incubated with microsomes, homogenates and kidney slices from
      the normal rat failed to induce lipid peroxidation. We show that the increase in
      TBARS in vivo detected by Ramsammy et al. was wrongly attributed to the oxidant
      power of gentamicin. As this antibiotic does react positively to thiobarbituric
      acid in the presence of a system generating free radicals, it is possible that
      these authors accidentally introduced such a system into their experiments.

PMID- 7725345
TI  - Benomyl affects the microtubule cytoskeleton and the glutathione level of
      mammalian primary cultured hepatocytes.
AB  - Rat primary hepatocyte cultures have been used to study the effect of Benomyl
      alone or in combination with Pirimiphos-methyl. The results presented demonstrate
      that Benomyl alone is responsible for the microtubular disorganization in both a
      time- and dose-dependent manner, that the effect is reversible after the agent is
      removed, and that Benomyl is a potent glutathione-depleting agent. Pirimiphos
      methyl, alone or combined with Benomyl had no effect on microtubule organization,
      but reinforced the decrease in glutathione.

PMID- 7725346
TI  - Differential effects of 3 dipyridyl isomers on hepatic microsomal cytochrome P450
      and heme oxygenase in rats.
AB  - We compared the effects of 3 dipyridyl isomers, 2,2'-dipyridyl, 2,4'-dipyridyl
      and 4,4'-dipyridyl, on hepatic microsomal heme oxygenase and drug-metabolizing
      enzyme activities in male rats. 2,2'-Dipyridyl increased cytochrome P450 (P450)
      content at lower doses, but decreased with increasing dose levels. Immunoblot
      analysis revealed that 2,2'-dipyridyl did not induce both P450 1A1/2 and P450
      2B1/2, in contrast to 2,4'- and 4,4'-dipyridyls, both of which were inducers of
      either P450 1A1/2 and/or P450 2B1/2. Some drug-metabolizing enzyme activities
      gradually declined with the increasing dose level of 2,2'-dipyridyl. 2,2'
      Dipyridyl was able to induce hepatic microsomal heme oxygenase in a dose
      dependent manner, but 2,4'- and 4,4'-dipyridyls did not, even at the highest dose
      (0.80 mmol/kg) examined. Treatment of rats with 2,2'-dipyridyl resulted in the
      increase of glutathione (GSH) content in a dose-dependent manner, but not 4
      substituted isomers. A time course study with 2,2'-dipyridyl revealed that it
      produced a significant decrease in hepatic GSH content at early time periods (2-6
      h) after its administration with an inverse increase in heme oxygenase activity.
      The present investigation has revealed that in contrast to the induction of P450
      by 4-substituted dipyridyl compounds, 2,2'-dipyridyl is a novel inducer of
      hepatic microsomal heme oxygenase, together with the change in hepatic GSH
      content. This study would provide information on the differential effects of
      simple dipyridyl isomers on hepatic enzymes involved in heme and drug metabolism.

PMID- 7725347
TI  - A comparison of the lactational and transplacental deposition of mercury in
      offspring from methylmercury-exposed mice. Effect of seleno-L-methionine.
AB  - Females exposed to methylmercury expose their offspring to mercury across the
      placenta as well as through milk. The relative importance of these two routes of
      exposure has hitherto been unresolved. Using a cross-fostering model with female
      mice, the transplacental and lactational exposures to mercury were evaluated
      separately. In female mice exposed to low, non-toxic levels of methylmercury in
      the drinking water the deposition of mercury in offspring before birth was
      quantitatively more important than later transfer of mercury from milk to
      offspring. Seleno-L-methionine supplementation of the dams increased the whole
      body deposition in offspring. As methylmercury is anticipated to be absorbed
      completely and the young mice are unable to excrete mercury, these data indicate
      that seleno-L-methionine affects the kinetics of the inorganic mercury pool,
      which, due to demethylating processes, is present in both blood and milk of
      methylmercury-exposed females.

PMID- 7725348
TI  - Binding of pesticides to alpha, mu and pi class glutathione transferase.
AB  - The binding of fluorodifen, fenarimol, acifluorfen, 2,4-DES, methyl parathion,
      paraquat and pyrazophos by alpha, mu and pi class glutathione transferases (GST)
      was determined by the 2-p-toluidinylnaphthalene-6-sulphonate (TNS) binding
      fluorescence inhibition technique. Although all the 3 GST classes appear to be
      capable of binding the pesticides investigated, mu class exhibited somewhat
      higher affinity than the alpha and pi classes.

PMID- 7725349
TI  - Inhibitors of renal chloride transport do not block toxicant-induced chloride
      influx in the proximal tubule.
AB  - We have previously demonstrated that chloride influx occurs during the late
      stages of mitochondrial inhibitor-induced renal proximal tubule (RPT) cell
      injury. The purpose of this study was to determine if chloride influx is a common
      pathway in toxicant-induced cell injury and if inhibitors of renal chloride
      transport block the chloride influx. Chloride influx occurred in the late stages
      of RPT cell injury induced by the diverse toxicants mercuric chloride, t-butyl
      hydroperoxide, bromohydroquinone, and tetrafluoroethyl-L-cysteine. Specific
      inhibitors of known renal chloride transport did not prevent antimycin A-induced
      chloride influx. Toxicant-induced chloride influx occurred prior to cell swelling
      and decreasing the extracellular chloride concentration diminished toxicant
      induced cell death. Thus, chloride influx is a common pathway in the late stages
      of toxic cell injury and does not occur through known mechanisms of renal
      chloride transport. Further, we propose that toxicant-induced chloride influx is
      mediated by a novel receptor related to the neuronal strychnine-sensitive glycine
      receptor and that chloride influx is a key step in cell swelling and lysis.

PMID- 7725350
TI  - Chromosome damage induced by carboplatin (CBDCA).
AB  - The chromosome damage induced by carboplatin (CBDCA) was evaluated in vitro. In
      human lymphocytes 5 micrograms/ml CBDCA produced a 7-fold increase in the
      frequency of sister chromatid exchanges (SCE) and a 3-fold increase in the number
      of cells with structural abnormalities compared with the control. Likewise, at
      this highest dose a significant increase was induced in the value of micronuclei
      (MN) and an important delay in the lymphocyte cycle progression was observed. In
      Chinese hamster ovary (CHO) cells, CBDCA showed a significant increase in
      chromosome aberrations (CA) at the doses assayed. The increase of SCE, CA and MN
      by CBDCA remained much lower than that produced by mitomycin C (positive
      control). The results suggest that CBDCA is a DNA-damaging drug with similar
      behaviour as an alkylating agent.

PMID- 7725351
TI  - [The study of a diagram of the dorsum of the tongue for determining individual
      identifying characteristics].
AB  - Patterns of the back of the tongue were studied in 80 normal subjects and 200
      corpses of both sexes to detect the individual personality characteristics. A
      technique of impression making using alginate mass and plaster casts has been
      developed. A chart and arithmetic scheme is offered for accurate presentation of
      the number and localization of papillae. Study of the patterns of the mucosa of
      the back of the tongue revealed individual features in the structure of sulcated,
      foliated, fungiform, and filiform papillae, which may be significant in
      identification expert evaluation.

PMID- 7725352
TI  - [Sex crimes committed by family members against children and adolescents].

PMID- 7725353
TI  - [Microscopic changes in the brain in combined poisonings with alcohol, morphine,
      psychotropic and soporific substances].

PMID- 7725354
TI  - [The preparation of an anti-A reagent from the lectin of hairy vetch (Vicia
      villosa) for detecting antigen A in human erythrocytes and saliva].
AB  - Anti-A reagent for the detection of the relevant antigen in human red cells and
      saliva has been developed. The reagent is prepared by dissolution of purified
      Vicia villosa lectin in the serum of group AB or B diluted 8 times with PBS. This
      solvent appreciably improves the anti-A selectivity of lectin and is used for
      titration. Purification of lectin by ammonium sulfate precipitation is described.
      The reagent agglutinates group A red cells in the minimal lectin concentration of
      2.5 to 10 micrograms/ml and does not agglutinate group 0 and B red cells in
      concentration 10 mg/ml. Moreover, the reagent is fit for the detection of antigen
      A in traces of blood and saliva by the absorption-elution method.

PMID- 7725355
TI  - [The thermal analytical characteristics of the shaft of human hair in order to
      determine sex and age].
AB  - Differential thermal and thermogravimetric analyses (DTA and TGA, respectively)
      of hairs at temperature range of 20 to 250 degrees C were carried out to
      determine the age and sex. Results of DTA and TGA unambiguously indicate that
      rhombic modification of sulphur (alpha-S) predominates in female hairs, whereas
      the monoclinal one (beta-S) prevails in male hairs whatever the age of examinees,
      that is, the sex can be identified with the use of these characteristics.

PMID- 7725356
TI  - [The forensic chemical determination of kurantil and verapamil].

PMID- 7725357
TI  - [The participation of the forensic physician in investigative actions to verify
      the evidence in cases of injuries from sharp implements].
AB  - The problem of contribution of a forensic medic to verification of testimony at
      the site of criminal event is seldom, if ever, discussed. Tasks facing the
      specialist, some aspects of preparation to work, and methods of verifying the
      testimony on the spot, when the details of infliction of injuries with sharp
      instruments are investigated (the most frequent cause for calling forensic medics
      to verification of testimony on the spot) are discussed.

PMID- 7725358
TI  - [The forensic medical assessment of light bodily injuries. 1].
AB  - The authors discuss the essence and the criteria of assessment of slight bodily
      injuries and subdivide such injuries into two categories: those involving short
      term health disorders and involving no disorders of this kind. They propose to
      alter the relevant sections of the actual "Regulations of the Forensic Medical
      Assessment of the Severity of Bodily Injuries".

PMID- 7725359
TI  - [Establishing the location of the driver and passenger with fastened seatbelts at
      the moment of a traffic accident].
AB  - The authors developed a method for determination of the place occupied by driver
      and passengers with fastened safety belts at the moment of a car accident. Traces
      impressions on the clothes, macro- and microelements of the clothes and safety
      belts not found in the control were obtained.

PMID- 7725360
TI  - [The use of monoclonal antibodies for analyzing clues of biological origin].

PMID- 7725361
TI  - [The dynamics of the early changes in the monoaminergic nervous apparatus of the
      spinal cord arteries in blunt trauma].
AB  - Changes in the adrenergic nervous system and population of tissue basophils of
      human spinal arteries in the course of 24 h after a blunt injury to the spine
      were studied. A staged pattern of development of compensatory adaptive reaction
      of the mechanisms regulating the spinal circulation has been revealed. The
      detected time course of posttraumatic changes may be interesting as it concerns
      the diagnosis of the time when a blunt injury to the spine was inflicted.

PMID- 7725362
TI  - [The action of tear-gas and irritant substances on the human body].

PMID- 7725363
TI  - [Injuries to the hyoid bone and laryngeal cartilages in hanging].

PMID- 7725364
TI  - [The fate of Marshall Lin Biao].

PMID- 7725365
TI  - [The 50th anniversary of the Department of Forensic Medicine of the Yaroslavl
      State Medical Institute].

PMID- 7725366
TI  - [The embedding of fragments of fabric and jersey fibers in the natural openings
      of the bones of the cranial vault in trauma from blunt solid objects].
AB  - The authors present data on the possibility of knocking in the fibers into the
      natural orifices of cranial vault bones during strikes inflicted with blunt
      instruments through textiles and jersey. Detection of such a sign indicates a
      strike through a tissue pad and shows the localization of the contact with the
      instrument.

PMID- 7725367
TI  - [The gas weapon--a new problem for forensic toxicology].
AB  - Current status of the problem of toxicologic assessment of irritants used for gas
      weapon charge is presented, classification and parameters of toxicity of clinical
      picture in poisoning with, and mechanisms of toxic action of irritants are
      described. Trends in research aimed at improvement of forensic medical diagnosis
      of lesions caused by irritants are discussed.

PMID- 7725368
TI  - Aminopyrine metabolism in man: the acetylation of aminoantipyrine cosegregates
      with acetylation of caffeine.
AB  - Aminopyrine and caffeine metabolism was evaluated in vivo in 21 healthy
      volunteers in order to elucidate whether the acetylation capacity of the two
      substances correlates. The ratio of the aminopyrine metabolites 4
      acetylaminoantipyrine (AAA)/4-aminoantipyrine (AA) was compared with the ratios
      of caffeine metabolites AAMU/1-X and AAMU/(AAMU + 1-X + 1-U). All the subjects
      phenotyped as slow acetylators with caffeine displayed AAA/AA ratios lower than
      3.4, whereas the extensive acetylators had ratios higher than 3.8. Therefore, the
      acetylator phenotype determined with caffeine cosegregated with the capacity to
      acetylate the aminopyrine metabolite AA. The N-demethylation of aminopyrine and
      caffeine correlated strongly in the subjects studied (p < 0.001). A highly
      significant correlation (r = 0.92; p < 0.001) was also observed between caffeine
      N(1)- and N(7)-demethylation activities. In addition, most N-demethylation steps
      of both drugs significantly correlated, suggesting partial contributions by
      identical or closely related enzymes in their metabolism.

PMID- 7725369
TI  - Time course of appearance of ofloxacin in human scalp hair after oral
      administration.
AB  - The time course of appearance of antimicrobial ofloxacin (OFLX) in human scalp
      hair was monitored in three healthy male volunteers after the oral administration
      of 100 mg OFLX three times daily for 2 consecutive days. Hair samples were
      collected from each subject by plucking several strands of frontal hair every day
      from 1 till 16 days after administration. A single hair was dissolved in 1 M NaOH
      to extract OFLX by chloroform, and the drug was measured by high-performance
      liquid chromatography and fluorescence detection. OFLX started to appear in the
      hair 1 to 3 days after administration and reached the maximal level approximately
      4 to 9 days, remaining at almost the same level thereafter. This finding suggests
      the slow transfer of OFLX from hair follicle cells to hair matrix may be due to
      the slow dissociation of OFLX from bound melanin.

PMID- 7725370
TI  - Modified enzyme-multiplied immunoassay technique valproic acid test kit.

PMID- 7725371
TI  - Systematic approach to a dosage regimen for phenytoin based on one-point, steady
      state plasma concentration.
AB  - A systematic approach to individualizing the phenytoin (PHT) dose from a previous
      dose (D) and steady-state concentration (Css) pair was established by the
      combined use of two methods based on recently reported population pharmacokinetic
      parameters. This system applies the Michaelis-Menten equation to the initial data
      pair (D1-Css1) and solves for (a) maximum metabolic rate constant (Vmax) assuming
      the population mean for the Michaelis constant (Km) (method 1), and (b) Km
      assuming the population mean for Vmax (method 2). The derived estimates of Vmax
      and Km are then put through a series of filters, which results in the selection
      of method 1 and/or method 2 or allocation of a third category that needs further
      evaluation. A simulation study was performed to find a series of filters. The
      presented approach was applied retrospectively to the patients' data of 35 sets.
      Accurate predictions of the Css error within 5 micrograms/ml were obtained in 84%
      of the 25 cases, and in 30% of the 10 cases excluded. This systematic approach
      gives better prediction performance in mean error, mean absolute error, and root
      mean square error than a Bayesian feedback method.

PMID- 7725372
TI  - Immunoreactivity of endogenous digitalis-like substances in cord blood sera
      studied with antidigitoxin monoclonal antibodies.
AB  - The presence of digitoxin-like immunoreactive substances, whose nature is yet
      unknown, has been demonstrated in the umbilical cord blood. We selected six
      antidigitoxin monoclonal antibodies (MAb) having different specificity profiles
      concerning digitoxin analogs and steroid hormones. These antibodies were tested
      in a digitoxin radioimmunoassay (RIA). With the help of this technique, we
      measured the concentrations of apparent digitoxin in the cord blood drawn either
      at birth or in utero from mothers not undergoing any digitalis treatment. In the
      cord blood of newborns, the concentrations of apparent digitoxin, measured by the
      two MAbs that have the highest cross-reactions with dehydroepiandrosterone (DHEA)
      (123A23 and 145A41), were two or three times higher than with the other
      antibodies. In the fetal cord blood, where the concentration of DHEA is five to
      seven times lower than that observed at birth, these antibodies revealed a
      threefold lower concentration of apparent digitoxin than that observed in blood
      drawn at birth. Furthermore, MAbs that had similar specificities towards
      digitoxin analogs and steroids showed different measurements of digitoxin-like
      concentrations. These observations suggest that digitoxin-like immunoreactive
      compounds detected by the RIA may constitute a group of different molecules, one
      of which would be the DHEA.

PMID- 7725373
TI  - Cisplatin pharmacokinetics using a five-day schedule during repeated courses of
      chemotherapy in germ cell tumors.
AB  - Total and ultrafilterable platinum (Pt) disposition was investigated during 49
      courses of chemotherapy in 13 patients with germ cell tumor treated with
      cisplatin (DDP), 20 mg/m2/day on 5 consecutive days. The following
      pharmacokinetic parameters were analyzed: distribution (t1/2 alpha) and
      elimination (t1/2 beta) half-lives, total body clearance (ClT), renal clearance
      (ClR), and areas under the concentration versus time curve (AUCs). Blood samples
      were collected immediately before and after DDP infusion (Day 1 through Day 5);
      in addition, on Day 5, samples were collected at 0.25, 0.5, 1, 8, 24, and 48 h
      after DDP infusion. Urine was collected during each day of treatment and up to 48
      h after the last DDP dose. During each chemotherapy cycle plasma levels of total
      and ultrafilterable Pt progressively increased from the first to the last day of
      treatment. At the first cycle, total Pt concentrations ranged from 0.67 to 1.46
      micrograms/ml (mean increase, 118%), and those of ultrafilterable Pt from 0.117
      to 0.205 micrograms/ml (mean increase, 75%). Mean +/- SD total Pt plasma levels
      immediately postinfusion increased from 0.67 +/- 0.20 microgram/ml at the first
      cycle (first day of therapy) to 1.13 +/- 0.21 microgram/ml at the same time point
      at the fourth cycle. Mean total Pt peak levels were reached at the end of
      infusion on the last day of each cycle, and increased from 1.46 +/- 0.29
      microgram/ml (first cycle) to 1.89 +/- 0.40 microgram/ml (fourth cycle). Total Pt
      was detectable in plasma before the beginning of all cycles following the first.
      As a result, AUC significantly increased and ClR significantly
      decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725374
TI  - Evaluation of a potential enantioselective interaction between ticlopidine and
      warfarin in chronically anticoagulated patients.
AB  - Ticlopidine is a novel antiplatelet drug reported to cause significant inhibition
      of several drugs metabolized by the hepatic cytochrome P-450 enzyme system,
      including antipyrine and theophylline. Warfarin, a racemic mixture of two
      enantiomers (R and S), is extensively metabolized by the CYP-450 system. S
      Warfarin is five to eight times as active as R-warfarin. The effects of
      ticlopidine on the pharmacokinetics and pharmacodynamics of warfarin were
      examined in nine elderly men (69 +/- 4 years) receiving long-term warfarin
      therapy. Steady-state warfarin enantiomer concentrations and International
      Normalized Ratios (INRs) were determined at baseline and after 14 days of
      treatment with oral ticlopidine, 250 mg twice daily. Warfarin enantiomer serum
      concentrations were determined by high-performance liquid chromatography after
      chiral derivitization. Ticlopidine co-medication resulted in a significant
      increase in mean R-warfarin concentrations (+25.7%, p < 0.05), while no
      significant difference in S-warfarin concentrations was noted (+0.8%). Mean INR
      values were not significantly different from the baseline (+8.3%), although
      substantial interindividual variability was noted. We conclude that ticlopidine
      co-medication does result in an enantioselective kinetic interaction with
      warfarin; however, this interaction is likely to be of minimal clinical
      significance in most patients.

PMID- 7725375
TI  - Potential of concentration monitoring data for a short half-life drug: analysis
      of pharmacokinetic variability for moclobemide.
AB  - The pharmacokinetic variability of moclobemide, a new short half-life reversible
      selective inhibitor of monoamine oxidase (MAO) was investigated through analysis
      of concentrations measured during early open clinical use. Eighty-nine depressed
      patients, aged 21-96 years, were included in the present study. Doses ranged from
      200 to 900 mg/day, and the time interval between blood sampling and last drug
      intake on the previous day was between 8 and 23 h. Intraindividual variability
      was generally moderate, with a few patients displaying consistently high
      concentrations despite moderate doses. Interindividual variability for measured
      concentrations was approximately 300-fold. After concentration decrease with time
      was taken into account (average half-life estimate of 4.6 h), age was identified
      as a major factor responsible for between-patient variability. Average
      concentration increase per decade of age was 38%. Neither gender, weight, height,
      smoking, nor alcohol intake explained a significant additional part of the
      variance. Analysis of residuals also suggested that phenytoin co-medication may
      induce moclobemide metabolism. The present study indicates that concentration
      monitoring of a newly marketed drug can contribute to gaining insight into its
      pharmacokinetic behavior and to enhancing its rational use in clinical practice.

PMID- 7725376
TI  - Factors influencing plasma concentrations of carbamazepine and carbamazepine
      10,11-epoxide in epileptic children and adults.
AB  - Plasma carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) concentrations
      were measured in 160 epileptic patients in order to determine the effect of
      factors such as age, daily dosing schedule, formulation, and combination with
      other antiepileptic drugs on these concentrations in relation to the daily dose.
      The results showed that the CBZ plasma level/dose ratio was affected by all
      factors studied, whereas the CBZ-E plasma level/dose ratio was affected only by
      formulation and age. The ratio of CBZ-E to CBZ plasma levels (CBZ-E/CBZ) was
      affected by daily dosing schedule, age, and combination with other antiepileptic
      drugs. The present study demonstrated that many factors affect plasma CBZ/dose
      ratios, explaining the discrepancies observed in the literature.

PMID- 7725377
TI  - Treatment of human serum with sulfosalicylic acid structurally alters digoxin and
      endogenous digoxin-like immunoreactive factor.
AB  - Pretreatment of human serum with 5-sulfosalicylic acid (SSA) as used in the
      Abbott TDx digoxin assay produces deglycosylated congeners of digoxin (DIG) and
      of endogenous digoxin-like immunoreactive factor (DLIF). Using high-performance
      liquid chromatography analysis, we observed differences in the degree and pattern
      of DIG breakdown products among five patients. The aglycone digoxigenin was the
      major product in several samples. Smaller amounts of the bis- and mono
      digitoxosides and unidentified products less polar than DIG were sometimes
      present. Treatment of DLIF-containing plasma with SSA produced similar patterns
      of DLIF-breakdown products. Incubation of normal plasma containing DIG with SSA
      for up to 30 min caused little change in measured DIG by TDx and radioimmunoassay
      (RIA) but decreased to 50% in the ACS DIG assay. These results are consistent
      with the near 100% cross-reactivities of deglycosylated DIG congeners in the TDx
      and RIA assays compared to their lower cross-reactivities in the ACS assay. We
      conclude that the breakdown of DIG and DLIF during treatment of serum with SSA
      may compromise the accuracy of TDx DIG assays and may explain discrepancies
      observed in other studies between digoxin immunoassays. This study underscores
      the importance of understanding the effects of pretreatment strategies used for
      analytes measured by immunoassay.

PMID- 7725378
TI  - Pharmacokinetic study of valproic acid sustained-release preparation in patients
      undergoing brain surgery.
AB  - Pharmacokinetics of valproic acid sustained-release preparation (VPA-SR) were
      studied in nine patients undergoing surgery for brain tumor. Total (t) and free
      (f) serum concentrations were analyzed in samples drawn during the day of brain
      surgery and compared with levels from a postoperative day. The area under the
      curve (AUCt) and clearance (CLt) of the total concentration did not differ on
      these occasions. In contrast, statistically significant differences were observed
      in AUCf and CLf between the two occasions; increased AUCf and decreased CLf were
      observed on the day of surgery. A significant relation was found between the
      average free fraction (AUCf/AUCt on operation day per AUCf/AUCt on postoperative
      day) and estimated blood loss during operation (r = 0.82; p < 0.001). In
      addition, a significant relation was found between simple free fraction and the
      intraoperative albumin level in serum (r = -0.68; p < 0.001). These findings
      indicate that the increased VPA free concentration is due to low serum albumin
      level secondary to blood loss and that there has been a decrease in intrinsic
      clearance during operation.

PMID- 7725379
TI  - Verapamil and norverapamil plasma levels in infants and children during chronic
      oral treatment.
AB  - Verapamil and norverapamil trough plasma levels were measured in 22 children,
      aged from 15 days to 17 years, under chronic oral treatment with the drug (mean
      daily dose +/- SD: 4.9 +/- 1.4 mg/kg) for supraventricular tachyarrhythmias (n =
      20) or hypertrophic cardiomyopathy (n = 2). Overall, 67 determinations were
      available (1 to 11 per patient) and the mean concentration values (+/- SD) were
      43.3 +/- 36.4 ng/ml for verapamil and 41.7 +/- 28.9 ng/ml for norverapamil.
      Verapamil and norverapamil trough concentrations were correlated with the daily
      dose (p < 0.05) but a wide intersubject variability was present at any given dose
      and the regression line did not pass through the origin of axes (x-axis
      intercept: 1.2 mg/kg for verapamil, 0.9 mg/kg for norverapamil). To study the
      influence of age on drug kinetics, verapamil plasma concentrations corrected by
      daily dose/kg ([V]/D) and norverapamil to verapamil concentration ratios (N/V)
      (taken as an index of metabolic clearance) were divided according to age
      quartiles. The median [V]/D was higher in the first and in the fourth age
      quartile than in the other two age groups. On the contrary, median N/V ratio
      increased with age, suggesting that drug metabolism was improving during the
      first year of life. Four children developed typical adverse reactions to the drug
      (bradycardia, AV block, hypotension). In one case verapamil plasma levels were
      definitely high (294 ng/ml). In the other three cases, concomitant factors (such
      as very young age and heart disease) seem to have contributed to drug toxicity.

PMID- 7725380
TI  - Evaluation and comparison of the TDxII, Stratus, and OPUS digoxin assays.
AB  - Three automated immunoassays for digoxin in serum were evaluated--Abbott TDxII,
      Baxter Stratus, and Behring OPUS. The accuracy and precision of the assays were
      assessed by weighed-in controls and an external quality control program.
      Coefficients of variation of all methods in serum were < or = 10% at weighed-in
      concentrations of digoxin of 1 and 2.5 micrograms/L. Accuracy relative to weighed
      in concentrations of 1 and 2.5 micrograms/L ranged from 98 to 126% for all
      methods. Comparative results from patient samples showed little difference
      between the TDxII and Stratus and a greater difference observed between the TDxII
      and OPUS assays. The detection of digoxin-free samples containing digoxin-like
      immunoreactive substances (DLIS) in neonatal cord blood, pregnant patients, and
      liver and renal recipients by each assay was then assessed. The TDxII exhibited
      the highest incidence of DLIS. This is evident in neonatal cord blood in which
      40.4% of samples tested positive. In comparison, the extent of DLIS detected by
      Stratus was less and OPUS exhibited no DLIS in any of the groups studied. A case
      study of a patient treated with anti-digoxin Fab fragments (Digibind) also was
      included for analysis by each method. Fourteen hours after Digibind
      administration, the TDxII registered a digoxin concentration of 49.5 micrograms/L
      compared with 3.73, 1.80, and 2.49 micrograms/L for Stratus, OPUS, and
      ultrafiltered TDxII methods, respectively. The results indicate that to determine
      the concentration of digoxin after the administration of Digiband, the OPUS or
      fluorescence polarization immunoassay (FPIA)-ultrafiltered samples by TDxII are
      the assays of choice.

PMID- 7725381
TI  - An inexpensive and sensitive method for the determination of quinidine in plasma
      by high-performance liquid chromatography with ultraviolet detection.
AB  - A sensitive, specific, and rapid high-performance liquid chromatographic method
      with ultraviolet detection for therapeutic drug monitoring of the cardioactive
      compound quinidine is described. The method uses only 50 microliters of serum,
      which is extracted into methyl-t-butylether at an alkaline pH and consequently
      reextracted into dilute hydrochloric acid. Quinidine is separated from quinine,
      the internal standard, and dihydroquinidine on a reversed phase C18 column. The
      minimum detectable amount is 1 ng injected on column. The method is both precise
      and accurate, as shown by the validation data presented, and can also be of use
      in pharmacokinetic investigations.

PMID- 7725382
TI  - High-performance liquid chromatography determination of dapsone,
      monoacetyldapsone, and pyrimethamine in filter paper blood spots.
AB  - A high-performance liquid chromatography method for the simultaneous analysis of
      dapsone (DDS), the major metabolite of DDS, monoacetyldapsone (MADDS), and
      pyrimethamine (PYR) was modified for capillary blood samples obtained by finger
      prick and dried on filter paper. Limit of quantitation using 150 microliters
      whole blood dried on filter paper was found to be 20 ng/ml for DDS and PYR and 15
      ng/ml for MADDS (precision < 15%). The clinically relevant concentrations of DDS
      are 50-2,000 ng/ml and for PYR 25-150 ng/ml. No interference from several drugs
      were observed. The accuracy of the filter paper method and the original whole
      blood method was almost comparable. Standardization could therefore be obtained
      by the more simple whole-blood method. Dried filter paper samples stored at 19-22
      degrees C were stable for months and for 2 weeks stored at 35 degrees C. The
      concentrations of simultaneously collected capillary blood and conventional
      venous blood samples correlated well. The present method using capillary blood
      dried on filter paper is reliable, simple, sensitive, and applicable in the field
      with limited technical facilities.

PMID- 7725383
TI  - Measurement of the active leflunomide metabolite (A77 1726) by reverse-phase high
      performance liquid chromatography.
AB  - The immunosuppressive activity of leflunomide is expressed after conversion to
      its pharmacologically active metabolite A77 1726. Leflunomide is a potent
      immunosuppressant that inhibits both T-cell and B-cell activity. To date, no
      pharmacokinetic data have been reported on leflunomide or A77 1726, primarily
      because of lack of a suitable method for its analysis. We describe here the
      development and evaluation of a reverse-phase high-performance liquid
      chromatographic (HPLC) method for the analysis of A77 1726 in whole blood or
      plasma from humans or rabbits. In human blood, the method exhibited good analytic
      recoveries from 78 +/- 13.5% to 108 +/- 4.8% (mean +/- SD) for drug
      concentrations ranging from 400 to 100,000 micrograms/L. When using a sample
      volume of 0.25 ml the sensitivity of the method was found to be 400 micrograms/L,
      with a working standard range of up to 200,000 micrograms/L. The sensitivity of
      the method can be increased to 40 micrograms/L when 1.0 ml of sample is used.
      Between-run coefficients of variation of 12.2 and 14.7% at A77 1726 mean
      concentrations of 1,006 and 8,146 micrograms/L were found for this method. No
      significant differences in recovery of drug were noted when either human or
      rabbit plasma or whole blood was used as the medium of analysis. In whole-blood
      specimens, A77 1726 was found to be stable for up to 10 days at -20 or -70
      degrees C.

PMID- 7725384
TI  - Response of EMIT amphetamine immunoassays to urinary desoxyephedrine following
      Vicks inhaler use.
AB  - The cross-reactivity of l-methamphetamine (l-desoxyephedrine) to the EMIT-d.a.u.
      class (EC) and EMIT-d.a.u. monoclonal amphetamine/methamphetamine (EM) assays was
      evaluated in urine specimens collected from six subjects using Vicks inhalers.
      The subjects were five men and a woman ranging from 27 to 47 years old. Four
      subjects used the inhaler as recommended by the manufacturer for five consecutive
      days; two subjects used double this dosage for three consecutive days. All urine
      voids were collected, totaling 132 specimens. All specimens were analyzed by the
      EC and EM assays. Specimens yielding a positive response were then analyzed by
      chiral and achiral gas chromatography/mass spectrometry (GC/MS). No specimen was
      positive by the EM assay, whereas 17 specimens yielded positive EC results. One
      subject for form the "as recommended" group had six positive specimens with
      maximum l-desoxyephedrine of 872 ng/ml. Both subjects using twice the recommended
      dosage had positive specimens, maximum l-desoxyephedrine of 1,560 ng/ml. No
      positive specimen contained > 200 ng/ml l-amphetamine.

PMID- 7725385
TI  - Development of a gas chromatography-mass spectrometry method for determination of
      ketamine in plasma and its application to human samples.
AB  - A sensitive and precise gas chromatography-mass spectrometry method with selected
      ion monitoring has been developed for identification and quantification of the
      phencyclidine derivative ketamine in human plasma. The assay is based on an
      alkaline extraction from aqueous to organic solvent from plasma and an efficient
      gas chromatographic separation on a DB-5 capillary column. The analytical
      procedure has a coefficient of variation of 0.7-6.2% and from 1.3 to 8.7% within
      day and from day-to-day analysis, respectively. The low level of sensitivity was
      10 ng/ml. It was used to measure low plasma concentrations in volunteers during
      ketamine-induced experimental psychosis. The method is not enantio selective.

PMID- 7725386
TI  - Cloning of a cDNA coding for the acetylcholine receptor alpha-subunit from a
      thymoma associated with myasthenia [correction of myastenia] gravis.
AB  - To investigate the role of the acetylcholine receptor (AchR) in the pathogenesis
      of paraneoplastic Myasthenia gravis (MG), we screened a cDNA library of a MG
      associated thymoma with a DNA oligonucleotide coding for aa 371-378, i.e. for
      part of the very immunogenic cytoplasmatic epitope (VICE-alpha, aa 373-380) of
      the human AChR alpha-subunit. We isolated two cDNA clones. Analysis of these
      clones has identified an open reading frame of 1371 bp, coding for the AChR alpha
      subunit. No point mutation, insertion or deletion could be detected. Since the
      thymoma did not contain thymic myoid cells, which normally express AChR, the
      origin of the AChR transcripts must be the tumor cells itself. These findings
      confirm former results, where AChR alpha-subunit sequences from MG-thymomas were
      amplified by PCR.

PMID- 7725387
TI  - Distribution of molecules mediating thymocyte-stroma-interactions in human
      thymus, thymitis and thymic epithelial tumors.
AB  - Two findings in thymic epithelial tumors are correlated with the occurrence of
      myasthenia gravis(MG): (1) the expression of an acetylcholine receptor (AChR)
      like-epitope in the neoplastic epithelium, and (2) the preservation of thymus
      like features in the neoplasms, indicated by the presence of immature thymocytes.
      On this background it has been proposed that paraneoplastic MG may start with an
      intratumorous abnormal T cell selection due to aberrantly expressed AChR-epitopes
      (self-peptides). As appropriate thymocyte-stroma-interactions are prerequisites
      for thymocyte development in the thymus (and probably in MG-associated thymic
      tumors, too), we analyzed the expression of CD28/B7(BB1), CD2/:LFA3, LFA-1/ICAM-1
      and VLA-4/VCAM-1 in human thymus and thymomas by immunohistochemistry. In normal
      thymuses and thymitis the stromal molecules were expressed at higher levels in
      the medulla than in the cortex. This was particularly true for B7(BB1) that was
      undetectable by immunoperoxidase techniques in the cortex. In contrast, cortical
      type thymic epithelial tumors (cortical thymoma and well differentiated thymic
      carcinoma), known to exhibit the highest association with myasthenia, expressed
      the stromal molecules at almost medullary levels. The findings may be a clue to a
      functional difference between neoplastic and normal cortical epithelial cells:
      while we find the former to have the capacity to present soluble antigen to
      antigen-specific CD4+ T cells in vitro, normal cortical epithelium failed to do
      so. This altered microenvironment in thymomas might contribute to the
      autoimmunization by stimulating mature recirculating AChR-specific T cells.

PMID- 7725388
TI  - Effect of bovine growth hormone administration on the pattern of thymic
      involution in mice.
AB  - Age-related decline of the thymus in mice was reversed by repeated injections of
      bovine growth hormone. After hormone administration that was begun at 5, 8, or
      11.5 months of age, the cortical volume fraction (Vc), cortical/medullary ratio
      (C/M) and thymocyte numbers found were in the range obtained with younger mice.
      Growth hormone injection reduced the slope of the curves for Vc and C/M as a
      function of age, indicating a slowing down of the involution process.

PMID- 7725389
TI  - Current status of the major histocompatibility complex in the rat.

PMID- 7725390
TI  - Cosmid cloning of the RT1.A encompassing region of the rat major
      histocompatibility complex.

PMID- 7725391
TI  - Fifty-six new microsatellite markers in the rat genetic linkage map.

PMID- 7725392
TI  - Analysis of a portion of the RT1 region containing H beta, H alpha, and DOa class
      II genes.

PMID- 7725393
TI  - Mechanism of interaction between 70-kd heat shock proteins and rat CD3+, 4-, 8-
      killer T cells--implication in tumor rejection activity.

PMID- 7725394
TI  - Molecular cloning of the rat CD3 zeta/eta/theta gene.

PMID- 7725395
TI  - Identification of the functional class I genes of the rat by cDNA cloning.

PMID- 7725396
TI  - Identification of complementary DNAs for RT1.A(n) and an additional class I
      molecule in the RT1n haplotype.

PMID- 7725398
TI  - RT1.Al and class I genes deleted in the mutant haplotype lm1 share a similar
      promoter region.

PMID- 7725397
TI  - A monoclonal antibody (L21-6) recognizing an invariant chain expressed on the
      cell surface in rats with the exception of the BN (RT1n): a study of tissue and
      strain distributions.

PMID- 7725399
TI  - Anti-ICAM-1/LFA-1 monoclonal antibody therapy prevents graft rejection and IDDM
      recurrence in BB rat pancreas transplantation.

PMID- 7725400
TI  - The EKER rat, a model of dominantly inherited cancer syndrome.

PMID- 7725401
TI  - Susceptibility to oil-induced arthritis in the DA rat is determined by MHC and
      non-MHC genes.

PMID- 7725402
TI  - Transforming growth factor beta and interferon gamma modulate the development of
      TH-1-mediated autoimmunity in susceptible and resistant strains of rats.

PMID- 7725403
TI  - Selection for susceptibility to experimental allergic encephalomyelitis also
      selects for high IFN-gamma production.

PMID- 7725404
TI  - Nitric oxide production during adjuvant-induced arthritis is associated with
      tumor necrosis factor genotype.

PMID- 7725406
TI  - Beige (bg) rat: its usefulness for examining the relation of mastocytosis to worm
      loss shown in DA strain infected with Hymenolepis diminuta.

PMID- 7725405
TI  - Responsible gene for hepatitis of the LEC rat (hts) is the homolog of the human
      Wilson's disease (WD) gene.

PMID- 7725407
TI  - Activation patterns of specialized dendritic cells of the gut-associated
      lymphatic tissues following heterotopic small bowel transplantation in a graft
      versus-host model of the rat.

PMID- 7725408
TI  - Microchimerism and liver graft acceptance.

PMID- 7725409
TI  - Donor-specific transfusion: critical role of class I antigen presenting molecules
      in rat liver transplantation.

PMID- 7725410
TI  - Enhanced sensitivity to endotoxin shock following liver transplantation.

PMID- 7725411
TI  - Analysis of immunosuppressive mechanisms in deoxyspergualin-treated rat renal
      transplants in the early postoperative phase.

PMID- 7725414
TI  - T-cell responses in the thymus after hepatic transplantation in the rat.

PMID- 7725412
TI  - Histologic changes of autonomic nerves following heterotopic cardiac
      transplantation in rats.

PMID- 7725413
TI  - Phenotype and function of dendritic cells derived from rat bone marrow cell
      cultures.

PMID- 7725415
TI  - Kinetic studies of alloantibody response to donor alloantigens following donor
      specific transfusion and lung transplantation in rats.

PMID- 7725416
TI  - Microchimerism and lung allograft acceptance.

PMID- 7725418
TI  - Detection of H-Y-reactive T lymphocytes in primary mixed lymphocyte reaction in
      DA rats.

PMID- 7725417
TI  - Elucidation of rejection mechanisms using the splenocyte injection model in
      concordant xenotransplantation.

PMID- 7725419
TI  - Graft-versus-host reactivity of rat T-cell subsets in isolated class I
      difference.

PMID- 7725420
TI  - Polymerase chain reaction of the rat sex-determining region of the Y-chromosome
      and its application to estimating a state of sensitization to minor
      histocompatibility antigen H-Y.

PMID- 7725421
TI  - Ischemia-reperfusion injury: the role of Kupffer cells in the production of
      cytokine-induced neutrophil chemoattractant, a member of the interleukin-8
      family.

PMID- 7725422
TI  - Analysis of deoxyspergualin-induced host resistance to graft-versus-host reaction
      induced with small bowel transplantation in rats.

PMID- 7725423
TI  - Protective effects of glutamine for cold-preserved small bowel grafts.

PMID- 7725424
TI  - Proliferative activity in the splenic compartment during hepatic allograft
      rejection in the rat.

PMID- 7725425
TI  - Orthotopic reduced-size hepatic transplantation in rats.

PMID- 7725427
TI  - Characterization of hepatic allograft infiltrates in rats pretreated with donor
      specific blood transfusion: the role of OX-22(-)CD4+ Th2-like cells.

PMID- 7725426
TI  - Paradoxical rejection pattern of donor small bowel in young F1-rats in a graft
      versus-host strain combination.

PMID- 7725428
TI  - Suppression of hepatic allograft rejection in the rat by mitomycin C-treated
      donor splenocytes: tissue distribution of donor class I major histocompatibility
      complex antigen-positive cells in the recipient.

PMID- 7725429
TI  - Effect of tetrahydropyranyladriamycin on concordant xenotransplantation in the
      splenocyte injection and heart transplantation model.

PMID- 7725430
TI  - Fate of intrasplenically transplanted allogeneic hepatocytes and fetal liver
      tissue in different rat strain combinations.

PMID- 7725431
TI  - Evaluation of serum IL-8 concentrations after orthotopic liver transplantation in
      rats.

PMID- 7725432
TI  - Plasma levels of hepatocyte growth factor in prolonging hepatic allografts in
      rats pretreated with donor-specific blood transfusion.

PMID- 7725433
TI  - Kidney graft quality: 490 kidneys procured from brain dead donors in one center.

PMID- 7725435
TI  - Consequences of brain death on myocardial metabolism: experimental study using
      31P-nuclear magnetic resonance spectroscopy.

PMID- 7725434
TI  - Influence of epinephrine treatment of the organ donor on acute tubular necrosis
      following renal transplantation.

PMID- 7725436
TI  - Ultrastructure of UVB-irradiated and organ-cultured human donor corneas.

PMID- 7725437
TI  - Experimental preservation of the heart transplant: effects of deferoxamine on
      functional recovery and lipid peroxidation of the isolated-perfused rat heart
      subjected to ischemia and reperfusion.

PMID- 7725438
TI  - Transesophageal echocardiography assessment of heart in brain dead patients
      before harvesting.

PMID- 7725439
TI  - Donor liver glutathion S-transferase activity during graft preservation.

PMID- 7725440
TI  - Activation of the endothelial cell in rat liver during preservation by cold
      storage.

PMID- 7725441
TI  - Extraction and purification of human pancreatic islets using automated methods:
      cryopreservation in dimethyl sulfoxide versus modified University of Wisconsin
      solution.

PMID- 7725442
TI  - Preliminary results of a survey on the information of families of organ and
      tissue donors.

PMID- 7725443
TI  - Donor factors influencing organ transplant prognosis.

PMID- 7725444
TI  - Specific anti-HLA antibody immunoadsorption with columns of fibroblasts or
      membrane proteins coupled to microcarriers--methodology.

PMID- 7725445
TI  - Differential IFN-gamma and IL-10 production by subsets of T lymphocytes
      corresponding to a differential outcome of human kidney grafts.

PMID- 7725446
TI  - Soluble HLA class 1 antigens in kidney allograft recipients.

PMID- 7725447
TI  - Allogenic microchimerism following auxiliary heterotopic liver transplantation in
      rat and swine.

PMID- 7725448
TI  - Human TNF-alpha induces major histocompatibility complex class-II molecules on
      porcine endothelial cells without affecting the proliferative response of human
      lymphocytes.

PMID- 7725449
TI  - Heart transplantation is a valid therapeutic option for anthracycline
      cardiomyopathy.

PMID- 7725450
TI  - Tracheal transplantation: an experimental technique with revascularisation and
      venous drainage.

PMID- 7725451
TI  - Recurrence of sarcoidosis in a human lung allograft.

PMID- 7725452
TI  - Predictors of late death in 5-year survivors of heart transplantation.

PMID- 7725454
TI  - Echocardiography is not a good way of monitoring cardiac grafts after abdominal
      heterotopic transplantation in the rat.

PMID- 7725453
TI  - Heart transplantation for valvular heart disease.

PMID- 7725455
TI  - An immunological score for prediction of acute rejection of heart transplants.

PMID- 7725456
TI  - Study of bone mineral density after cardiac transplantation.

PMID- 7725459
TI  - No requirement of fresh frozen plasma during liver transplantation: preliminary
      study.

PMID- 7725458
TI  - Fungal infections in lung transplant recipients.

PMID- 7725457
TI  - Combined heart and kidney transplantation.

PMID- 7725460
TI  - Long-term results of ABO-incompatible liver transplantation.

PMID- 7725461
TI  - Liver transplantation for hepatitis C virus cirrhosis: risk factors of graft HCV
      infection.

PMID- 7725462
TI  - Liver transplantation in end-stage biliary cirrhosis in infants weighing less
      than 12 kilograms.

PMID- 7725463
TI  - Liver transplantation in children with inherited metabolic disorders.

PMID- 7725464
TI  - Surgical technique of left lateral hepatic lobectomy in a related living donor
      for pediatric transplantation.

PMID- 7725466
TI  - Renal function after orthotopic liver transplantation without inferior vena cava
      occlusion.

PMID- 7725465
TI  - Post-liver transplantation thrombocytopenia: a persistent immunologic
      sequestration?

PMID- 7725467
TI  - Intrahepatic portocaval shunt in patients waiting for transplantation.

PMID- 7725469
TI  - Biliary duct lesions following xenogeneic liver and peripheral blood lymphocyte
      grafts in SCID mice.

PMID- 7725468
TI  - Perfecting a model of orthotopic liver/small bowel transplantation in pigs:
      determination of the best harvesting and transplantation technique.

PMID- 7725470
TI  - Blood transfusions under cyclosporine coverage before renal transplantation in
      children.

PMID- 7725473
TI  - Automated renal transplant biopsy with real-time ultrasonic guidance.

PMID- 7725471
TI  - Follow-up of renal allograft recipients from HBsAg positive donors. GCIF.

PMID- 7725474
TI  - Combined liver-kidney transplantation for primary hyperoxaluria: a report of two
      cases.

PMID- 7725472
TI  - CD4 and CD25 monoclonal antibody cocktail in kidney transplant rejection
      prophylaxis: clinical results of a pilot study.

PMID- 7725476
TI  - Toxoplasmosis in two renal transplant recipients: diagnosis by bone marrow
      aspiration.

PMID- 7725475
TI  - Cryptococcosis after renal transplantation.

PMID- 7725477
TI  - Hepatitis C virus infection in renal transplantation.

PMID- 7725480
TI  - False-positive p24 antigenaemia detected in renal allograft recipients: possible
      role of rabbit antithymocyte globulins.

PMID- 7725478
TI  - Dialysis arthropathy after renal transplantation.

PMID- 7725479
TI  - Impact of HLA-DR matching assessed by genomic analysis in long-term kidney
      allograft survivals.

PMID- 7725482
TI  - Treatment of kidney graft lithiasis.

PMID- 7725481
TI  - Azathioprine-induced pancytopenia in homozygous thiopurine methyltransferase
      deficient renal transplant recipients: a family study.

PMID- 7725483
TI  - Flow-cytometry monitoring of antilymphocyte globulin therapy in pediatric renal
      transplantation.

PMID- 7725484
TI  - Severe recurrence of type I membranoproliferative glomerulonephritis after
      transplantation: remission on steroids and cyclophosphamide.

PMID- 7725485
TI  - Late relapse of rapidly progressive glomerulonephritis (RPGN) in a transplant
      patient: efficacy of apheresis.

PMID- 7725486
TI  - Mass isolation of human islets of Langerhans favored by the prior development of
      a semiautomatic technique in the pig model.

PMID- 7725487
TI  - Evaluation of pancreas grafts in the Wistar rat after variable perfusion flow
      rates in two organ procurement procedures.

PMID- 7725488
TI  - Extraperitoneal placement of the bladder-drained pancreas transplant: why not?

PMID- 7725489
TI  - Hemolysis after kidney transplant with and without whole pancreas
      transplantation.

PMID- 7725490
TI  - Pregnancy after pancreas transplantation: report of a new case.

PMID- 7725491
TI  - Tumours in kidney-transplanted patients: a comprehensive one-centre study.

PMID- 7725492
TI  - Incidence of noncutaneous malignancies in kidney transplant recipients: a 20-year
      follow-up.

PMID- 7725493
TI  - Cancers following thoracic organ transplantation: a single center study.

PMID- 7725494
TI  - Aggressive squamous cell carcinomas in organ transplant recipients.

PMID- 7725495
TI  - Incidence of cutaneous tumors in kidney transplant patients: a 20-year follow up.

PMID- 7725496
TI  - Lymphoproliferative disorders in four orthotopic liver transplant patients.

PMID- 7725497
TI  - T-cell gamma-delta lymphoproliferative disorders after renal transplantation.

PMID- 7725498
TI  - Epstein-Barr virus lymphoblastoid cell lines from transplanted patients induce B
      lymphomas in SCID/hu mice: study of EBV replication.

PMID- 7725499
TI  - Post-transplant B-cell lymphomas--correlation of late stage B-cell
      differentiation and progression of disease; treatment with chimeric monoclonal
      antibody.

PMID- 7725500
TI  - Decreased incidence of lymphomas after heart transplantation under low-dose
      immunosuppression.

PMID- 7725501
TI  - Primary brain lymphoma in a renal transplant patient: unsuccessful intrathecal
      treatment with anti-B cell monoclonal antibodies (anti-CD21).

PMID- 7725502
TI  - Liver B cell lymphoma after liver transplantation.

PMID- 7725503
TI  - Hodgkin's disease and cadaveric renal transplantation.

PMID- 7725504
TI  - Hodgkin's disease after renal transplantation.

PMID- 7725505
TI  - Host renal cell carcinoma in kidney transplanted patient: ultrasonography
      screening study.

PMID- 7725506
TI  - Inadvertent transfer of choriocarcinoma with renal transplantation:
      characteristics of the donor-recipient pairs.

PMID- 7725507
TI  - Graft of a trophoblastic neoplasia by a kidney transplant.

PMID- 7725508
TI  - Liver transplantation in patients with preexisting malignancy.

PMID- 7725509
TI  - Quality of life after liver transplantation for cancer.

PMID- 7725513
TI  - Berger's disease in living-related donors.

PMID- 7725510
TI  - Recurrence of hepatocellular carcinoma in cirrhotic patients after liver
      resection or transplantation.

PMID- 7725512
TI  - Effect of cyclosporine administration on vascular reactivity of the isolated
      mesenteric bed.

PMID- 7725511
TI  - Renal transplantation and dyslipidemia: characterization of a population and
      treatment with diet and low dose lovastatin.

PMID- 7725514
TI  - HLA antigen expression and panel reactive antibodies.

PMID- 7725516
TI  - Pharmacokinetics of oral cyclosporine A in stable kidney transplant recipients: a
      critical review.

PMID- 7725515
TI  - Preliminary pharmacokinetic evaluation of a new galenical formulation of oral
      cyclosporine A: Neoral TM.

PMID- 7725517
TI  - Loss of renal allograft function caused by Histoplasma capsulatum.

PMID- 7725518
TI  - Strategy for improvement of graft survival in kidney recipients of nonrelated
      living donors.

PMID- 7725519
TI  - Liver function tests in hepatitis C virus infected kidney transplant recipients.

PMID- 7725520
TI  - Kidney allograft outcome analyzed by donor-reactive antibodies after
      transplantation.

PMID- 7725521
TI  - Morbidity after renal transplantation: role of bacterial infection.

PMID- 7725522
TI  - Combined kidney and pancreas transplantation: a Latin American center experience.

PMID- 7725523
TI  - Transplant coordinators in Rio Grande Do Sul: evaluation of activities.

PMID- 7725524
TI  - Pediatric renal transplantation in the state of Rio Grande Do Sul, Brazil.

PMID- 7725525
TI  - Comparative study of two protocols for living-related renal transplantation:
      donor-specific transfusion versus cyclosporine.

PMID- 7725526
TI  - Pediatric renal transplantation in a single center from Brazil.

PMID- 7725527
TI  - Attitudes and awareness regarding organ donation in the western region of Sao
      Paulo, Brazil.

PMID- 7725528
TI  - Oxidative damage markers in a renal ischemic-reperfusion model: the protective
      effect of monoamine oxidase inhibition.

PMID- 7725529
TI  - Monoamine oxidase inhibition prevents ischemia reperfusion damage in rat kidneys.

PMID- 7725530
TI  - Economic analysis of Sandimmune Neoral in Canada in stable renal transplant
      patients.

PMID- 7725531
TI  - A double-blind randomized study of Sandimmun Neoral versus Sandimmun in new renal
      transplant recipients: results after 12 months. The International Sandimmun
      Neoral Study Group.

PMID- 7725532
TI  - Effect of lovastatin and bezafibrate on cyclosporine-induced hyperlipidemia in
      rabbits.

PMID- 7725534
TI  - Late hepatic allograft failure associated with diffuse biliary sclerosis and
      ductal proliferation.

PMID- 7725535
TI  - Lactate dehydrogenase isoenzyme LD5/LD2 ratio as an indicator of early graft
      function and complications following pediatric orthotopic liver transplantation.

PMID- 7725533
TI  - Reduction of primary nonfunction with prostaglandin E1 after clinical liver
      transplantation.

PMID- 7725536
TI  - Antioxidative vitamins reduce fibrous tissue overgrowth of the bioartificial
      pancreas.

PMID- 7725537
TI  - Organ preservation by a new pulsatile perfusion method and apparatus.

PMID- 7725539
TI  - Decapitation of a pregnant sheep: a contribution to the brain death controversy.

PMID- 7725538
TI  - Modulation of neutrophil infiltration through nitric oxide in the ischemic rat
      kidney.

PMID- 7725541
TI  - Organ donation awareness: knowledge, attitudes and beliefs in a Puerto Rican
      population.

PMID- 7725542
TI  - Suppression of corneal allograft rejection after penetrating keratoplasty by
      antibodies to ICAM-1 and LFA-1 in mice.

PMID- 7725543
TI  - Identification of primary source of oxygen radicals in hepatic reperfusion
      injury: use of novel leucocyte removal system and nitro blue tetrazolium
      perfusion.

PMID- 7725540
TI  - The myth of presumed consent: ethical problems in new organ procurement
      strategies.

PMID- 7725544
TI  - Systemic and hepatic circulatory responses caused by head tilting in liver
      transplanted pigs.

PMID- 7725545
TI  - [Deep-freezing of semen from cancer patients--a public task?].

PMID- 7725546
TI  - [Quality of cryopreserved ejaculate in Hodgkin disease].
AB  - Each year approximately 70 males are diagnosed with Hodgkin's disease (HD) in
      Denmark. Most of these are less than 50 years of age. Since chemotherapy and
      radiotherapy may induce infertility in about 80% of patients, it has become
      routine to offer cryopreservation of semen prior to initiation of treatment. In
      41 men aged 17-42 years at diagnosis we evaluated the quality of semen (according
      to the WHO criteria) prior to cryopreservation and after thawing. The median
      sperm concentration at the time of diagnosis was 33 x 10(6)/ml (range: 0.3-458 x
      10(6)/ml) and positively correlated to age (rs = 0.36 p = 0.02) and to the
      histopathological classification (highest for patients with nodular sclerosis (p
      = 0.04) but not to semen volume, stage or presence of B-symptoms. The percentage
      of motile spermatozoa (range: 0-90%, median value 72%) was correlated to the
      sperm concentration; but not to any of the other parameters studied. Prior to
      freezing, 19 of 41 patients had normal semen quality according to the WHO
      criteria, whereas following thawing this was the case for only 14 semen samples.
      Ten of 23 patients with nodular sclerosis HD had normal semen quality (according
      to the WHO criteria) after thawing whereas this was the case for only 2 of 15
      patients with mixed cellularity HD (p = 0.05). Cryopreservation of semen may
      secure the possibility of fathering children for patients with HD following
      therapy, and is to be recommended.

PMID- 7725547
TI  - [Alcohol and the heart].
AB  - Structural cardiac morphological changes develop in a considerable number of
      chronic alcoholics, and preclinical cardiomyopathy is frequent especially among
      those with alcoholic liver disease. Alcohol exerts an acute albeit transient
      toxic effect on cardiac performance resulting in an impaired contraction of the
      myocardium. The effect is dose-dependent at rest, whereas compensatory mechanisms
      counterbalance the alcohol-induced changes during exercise. Similar
      cardiovascular reactions are recorded in patients with coronary artery disease,
      in whom the vasodilatory effect is measurable. In predisposed individuals heavy
      alcohol intake may induce atrial fibrillation or even malignant arrhythmias.
      Arterial hypertension is often found during the period following an alcohol
      excess, but this effect seems to be reversible. Alcohol intake inhibits
      aggregation of blood platelets and induces an increase in the level of high
      density lipoprotein cholesterol inhibiting atherogenesis. These mechanisms may
      well be dominant factors in the interpretation of the obvious protective effect
      of alcohol as seen in the U- or J-shaped relation between daily alcohol
      consumption and rate of survival. This relation clearly demonstrates a lower
      mortality among people consuming one to two drinks per day compared with both
      those who drink more and with alcohol abstainers, justifying that these people
      should continue their drinking habits unless they have diseases contraindicating
      alcohol consumption or have an increased risk of developing chronic alcoholism.

PMID- 7725548
TI  - [Transcutaneous evaluation of icterus in healthy mature newborn infants. A
      substitution for blood tests].
AB  - The conventional determination of plasma bilirubin concentration in the icteric
      mature healthy newborn infants may frequently be replaced by transcutaneous
      assessment. Depending on the desired exactitude and the prevailing consensus on
      plasma bilirubin determination it is possible to halve the necessary number of
      blood tests. However, the yellow colour of the skin is influenced by several
      factors. Thus, transcutaneous measurements of the plasma bilirubin concentration
      are inaccurate. The yellow colour of the skin should be considered as an
      important parameter which, at least theoretically, provides information
      concerning the risk of bilirubinencephalopathy beyond the mere relationship to
      the plasma bilirubin concentration. Introduction of the method as a test of
      hyperbilirubinaemia requires taking a stand on several practical circumstances,
      determination of a standard curve with the risk of selection borne in mind and
      the establishment of cut-off levels.

PMID- 7725549
TI  - [Prader-Willi syndrome--clinical picture and genetics].
AB  - Characteristics are hypotonia, problems with feeding and thriving in the neonate
      and infant, later hyperphagia and severe obesity. Other findings are dysmorphic
      traits, hypogonadism, short stature, developmental delay, mental retardation and
      behavioural problems. Diabetes mellitus (NIDDM) is frequent in adults. Treatment
      is symptomatic. Prognosis is determined by obesity. PWS occurs almost always
      sporadically and is found in all ethnic groups and in both sexes. The
      epidemiology of PWS in Denmark is unknown. In 95% of cases with PWS cytogenetic
      and molecular genetic investigations show either deletion of the paternal
      chromosome 15q11q13 or uniparental maternal disomy of chromosome 15. Since 1992
      150 bloodsamples of patients suspected for PWS have been investigated by
      cytogenetic and molecular genetic techniques at the John F. Kennedy Institute, DK
      2600 Glostrup; deletion of the paternal chromosome 15 was found in 15 and
      uniparental maternal disomy of chromosome 15 in eight cases.

PMID- 7725550
TI  - [Occupation and lumbar disk prolapse].
AB  - All Danish occupational groups were screened for an increased risk of
      hospitalization due to a prolapsed lumbar intervertebral disc (PLID) (ICD-8:
      725.11). A cohort of all gainfully employed Danes aged 20 to 59 years in 1981 was
      followed-up for 10 years for first hospitalization with PLID. A Standardized
      Hospitalization Ratio was calculated using all economically active persons as the
      reference group. Male groups with an elevated risk were found in building and
      construction, the iron and metal industry, in the food and nutrition sector and
      in occupational driving. Almost all groups of professional drivers had an
      elevated risk. Female groups with an elevated risk were mainly found in the same
      industries, but home helps, service workers in the private sector and sewing
      machine operators also had an elevated risk. We conclude that there are
      significant and systematic differences between occupational groups as concerns
      the risk of hospital admission due to PLID.

PMID- 7725552
TI  - [Augmentation ileo-cystoplasty in women with disabling urge incontinence].
AB  - The results after "clam"-augmentation cystoplasty are assessed in 11
      consecutively operated women aged 35-78. All were suffering from severe urgency.
      Eight were urge-incontinent and six of these stress-incontinent as well. Nine
      patients had been operated before with a total of 14 operations. Bladder
      distension and parasympatholytic medication had been tried in two and seven
      instances respectively. One patient died of a pulmonary embolism three weeks
      postoperatively. Follow-up ranged from 12-52 months, mean 29 months. Eight (80%
      (44-97)%) of the remaining 10 patients were cured with respect to urgency. One
      patient was improved, and one unchanged. Three (60% (15-95)%) out of five
      previously stress-incontinent patients were dry, one was improved and one
      unchanged in spite of a subsequent stamey urethrosuspension. Eight patients (80%
      (44-97)%) had spontaneous micturition, one used self-catheterisation once daily
      and one patient was retained on an indwelling catheter. It is concluded that
      augmentation cystoplasty is a procedure of considerable value in patients with
      disabling non-neurogenic urgency, where conservative therapy and previous surgery
      has failed.

PMID- 7725553
TI  - [Arteriohepatic dysplasia (Alagille syndrome)].
AB  - Alagille syndrome (AS) is the second most frequent cause of intrahepatic
      cholestasis in children under one year of age. The disease has an autosomal
      dominant mode of inheritance with reduced penetrance and variable expressivity.
      It has been stated that this form of biliary paucity has a good long-term
      prognosis, but recent studies have revealed that the syndrome may be accompanied
      by long-term manifestations extending beyond childhood. Based on a case story the
      syndrome is described, and the diagnostic criteria, treatment and prognosis of AS
      are discussed.

PMID- 7725551
TI  - [Alcohol, drugs and narcotics in suicides in the Aarhus police district].
AB  - For a period of one year all suicides in Aarhus police district were investigated
      with a view to identifying the presence of alcohol or drugs in the body of the
      deceased. Fifty-one suicides occurred, 46 of which were examined. One third of
      the suicides were due to poisoning and one fourth to hanging. Alcohol was
      detected in 20% and drugs or narcotics were found in approximately 60%. The most
      frequent findings were benzodiazepines, analgetics, antidepressants and carbon
      monoxide. Approximately 40% of the deceased had received psychiatric treatment.

PMID- 7725554
TI  - [Fatty acids and confusing signals].

PMID- 7725556
TI  - [Treatment of severe staphylococcal infections].

PMID- 7725555
TI  - [Sexuality and secondary sterility--on the necessity of focusing on sex in
      medicine].

PMID- 7725557
TI  - [Forensic genetics].

PMID- 7725558
TI  - [Gatroesophageal reflux in pregnant women].
AB  - Heartburn is a common symptom in pregnancy, affecting about two-thirds of
      pregnant women. The aetiology of gastro-oesophageal reflux in pregnancy is
      multifactorial. Reduced lower basal gastro-oesophageal sphincter pressure,
      increased intragastric pressure, delayed intestinal transit time and
      duodenogastric reflux have been found in pregnant women with heartburn, all
      factors which dispose to increased gastro-oesophageal reflux. Gastric emptying is
      apparently normal during pregnancy, but delayed during delivery. Therapy involves
      lifestyle modification and nonsystemic medication as the initial choices. H-2
      antagonists should only be used in severe and refractory cases.

PMID- 7725559
TI  - [Psychosocial aspects of disseminated sclerosis].
AB  - Using multiple sclerosis as a model, it is demonstrated how a chronic
      neurological disorder has psychosocial consequences during the period between
      onset and diagnosis, at the time of diagnosis, and in the post-diagnostic period.
      The impact of the disorder on self-esteem, civil status, habitation, economy,
      social and leisure activities and need for help is described. It is concluded
      that it will increasingly be expected that the physician has knowledge of these
      relations.

PMID- 7725560
TI  - [Rectal exploration and transrectal ultrasound scanning of rectal cancer. A
      prospective, blind study].
AB  - Staging of rectal carcinoma before surgical treatment was performed in a
      prospective blind study, comparing digital rectal exploration and transrectal
      linear ultrasonography (TRUS) with the resulting pathological examination. TRUS
      underestimated the depth of penetration in three of 33 patients and overestimated
      it in nine of 74. The figures for digital examination were five of 18 and 20 of
      76, respectively. Penetration of the rectal wall was correctly identified in 56
      of 61 patients by digital rectal examination and in 59 of 61 by TRUS. Specimens
      without penetration of the rectal wall were identified in 26 of 33 patients by
      TRUS, but in no more than 13 of 33 by digital examination. Regional lymph node
      metastases were present in 19 patients; none were diagnosed by digital
      examination, but TRUS identified 11 of the 19. It is concluded that TRUS will
      result in more patients being given the possibility of curative local surgery.

PMID- 7725561
TI  - [Fear of dental treatment. Prevalence and characteristics among adult Danes].
AB  - A random sample of residents of the municipality of Aarhus were telephone
      interviewed about fear of dental treatment and characteristics of any pre
      existing dental anxiety. Results showed that 4.2% of 539 residents surveyed had
      extreme anxiety and 6% were moderately afraid. Results of dental anxiety,
      especially in the odontophobic group, were years of avoidance of treatment and
      associated poor subjective perceptions of oral health. Logistic analyses revealed
      that although dental drilling was the identifying feature of dental anxiety
      characteristics, the drill could be symbolic for the many persons who perceived
      dentists as treating them with putdowns, angry comments and hardhandedness. Other
      persons suffered from multiple fears, which may have an accumulative effect on
      dental treatment anxiety. A conceptual model is presented as derived from present
      results and existing clinical and epidemiologic literature.

PMID- 7725562
TI  - [Symptoms of depression in cancer patients undergoing chemotherapy].
AB  - Symptoms of depression and anxiety were measured in a prospective follow-up study
      of 36 cancer patients before and during chemotherapy by means of the Hamilton
      rating scales and the Melancholia Scale. These scales proved useful in the
      examined population. Moderate or severe depression was seen in almost half of the
      patients before chemotherapy, but this figure decreased during follow-up. The
      symptomatology resembled that of primary depression, and the brief rating scales
      for depression seemed suitable for screening purpose. Problems in identifying
      morbid states of anxiety and depression are discussed.

PMID- 7725563
TI  - [Geographic variations in first-admission rates for patients with mental
      disorders in Denmark 1971-1990].
AB  - In the period 1971-1990 the first admission rate to Danish psychiatric hospitals
      and wards decreased by approximately 45%. This might reflect the similar decrease
      in number of available psychiatric beds. Generally, the decrease of first
      admission rates was larger in the metropolitan area than in the rest of the
      country. Consequently, the disparity in admission rates between town and country
      was reduced. This is probably due to the decentralization initiated in the mid
      seventies when the counties were made responsible for the psychiatric services in
      Denmark. Furthermore, changes in morbidity could add to the occurrence of
      regional variations. Number of available beds has gained increasing importance as
      a predictor of variations between counties and municipalities whereas the
      importance of distance to hospital and degree of urbanization has declined. As
      regards sociodemographic variables special importance should be attached to
      variables for the amount of social aid and the employment rate in the social and
      health sector. However, it is generally difficult to determine whether regional
      variations are due to differences in treatment facilities or morbidity
      differences.

PMID- 7725564
TI  - [Lumbar disk prolapse. A comparison of expected and observed waiting time for
      surgery].

PMID- 7725565
TI  - [Is methicillin better than cloxacillin in serious infections caused by strong
      penicillinase-producing staphylococci (phage-type 94/96)?].
AB  - An intravenous drug addict was treated with cloxacillin for septicaemia with
      Staphylococcus aureus because of pneumonia and suspected endocarditis. After 51
      days of treatment Staphylococcus aureus was still found in blood and expectorate
      despite continued treatment with intravenous cloxacillin 1 g three and later four
      times daily and oral rifampicin. The staphylococcal isolates were all of phage
      type 94/96. Investigations have shown that Staphylococci aurei of phage type
      94/96 produce large amounts of penicillinase, and that methicillin is the most
      penicillinase-resistant of the penicillinase-resistant penicillins followed by
      dicloxacillin and cloxacillin. The penicillinase production of the patient's
      Staphylococcus aureus strain was 304-362 units per mg bacteria which is high
      compared to typical values of 50-200. After 50 days of cloxacillin treatment, the
      treatment was changed to methicillin 2 g four times daily. Within a week the
      staphylococci had disappeared from the expectorate, and were never again
      recovered from the blood. It is suggested that methicillin should have superior
      efficiency in serious infections with Staphylococcus aureus of phage type 94/96.

PMID- 7725566
TI  - [Spinal fractures in adults in bob-sled accidents].
AB  - A case study of two adults who sustained severe burst fractures of the
      thoracolumbar spine (T12, L1) after trivial accidents using plastic sledges. In
      one case a transient conus medullaris lesion was encountered. The fractures were
      reduced indirectly by internal fixation as well as by direct anteposition of the
      fragments from the spinal canal after laminectomy. The fracture mechanism is
      probably a result of hyperflexion combined with very little shock absorbtion from
      this sledgetype. Plastic sledges seem particularly hazardous for adults.

PMID- 7725567
TI  - [Micro-mercurialism and medical ethics].

PMID- 7725568
TI  - [Stress-induced abdominal pain or Helicobacter pylori infection?].

PMID- 7725569
TI  - [On rabies, ignorance and humility].

PMID- 7725570
TI  - [Smoking cessation and nicotine therapy].

PMID- 7725571
TI  - Implementation of an NSOM system for fluorescence microscopy.
AB  - We describe our progress toward an NSOM system intended for fluorescence imaging
      of biological samples. This process included integration of shear-force feedback
      into an existing NSOM system. Topographic images acquired using uncoated tips are
      presented. We also present our initial effort at simultaneous acquisition of
      topographic and fluorescence data using an aluminum coated tip.

PMID- 7725572
TI  - [Suppurative otitis media, bacteriologic study and therapeutic management].
AB  - The patients of the ENT clinic at the Gabriel Ture hospital (Bomako, Mali)
      suffering from otitis media purulenta (96 patients under 70) were examined for
      pathogenetic agents in their purulent exudate. The infection was found in 96.9%
      of the samples. Monoflora dominated in 74%, mixed flora in 26% of the examinees.
      The patients received antibiotics. The antibioticograms proved high effectiveness
      of gentamycin, colistin, sisomicin and cefatoxin in the treatment of acute and
      chronic otitis media purulenta.

PMID- 7725573
TI  - [Otoneurologic symptoms of temporal pyramidal neoplasms].
AB  - The paper reports 3 cases of primary tumors in the temporal bone. The diagnosis
      was confirmed clinically, by CT and NMR-tomography findings. The pyramid tumors
      are characterized by involvement of the VII and VIII nerves and tactile disorders
      on the anterior and middle tongue. The images obtained visualized destruction
      foci. When the tumor spreads to the top of the pyramid, it destroys the function
      of the acoustic tube, the tympanic membrane acquires remarkable sucked-in
      appearance. Symptoms of focal neurological affection are usually absent,
      intracranial pressure is not elevated. The symptom complex may be incomplete
      depending the tumor location on the pyramid. Tumor lesion occurs in the pyramid
      or may invade the posterior cranial fossa.

PMID- 7725574
TI  - [Predictions of occupational noise-induced hearing loss].
AB  - Mathematical modelling is attempted to prognosticate occupational hypoacusis by
      Robinson's formula, 1999 International standard (1990), first-hand experience
      gained in hearing control in subjects occupationally exposed to noise and
      domestic expert criteria of hearing loss quantitation. Factors of risk to develop
      hypoacusis in noisy environment were put to the correlation analysis which showed
      their pathogenetic significance in the internal ear cochlear affections.

PMID- 7725575
TI  - [Etiology and treatment results of laryngeal and tracheal stenosis].
AB  - The paper provides results of examinations and surgical treatment in 190 patients
      with laryngeal and tracheal stenosis of different origin. The most favourable
      results were obtained in patients with postresuscitation stenosis, middle
      paralysis, posttraumatic stenosis: up to 75%, 71% and 55% of the responders,
      respectively. The canule remains for life in 20% of the surgical patients,
      because they have severe laryngeal and tracheal deformities associated with other
      affections.

PMID- 7725576
TI  - [Endoscopic diagnosis and treatment of cicatricial esophageal strictures].
AB  - The paper summarizes the experience gained by the authors in 10-year treatment of
      esophageal cicatricial strictures. Work-up and treatment results available on 107
      relevant patients provided evidence on the leading role of endoscopic diagnosis
      in cicatricial strictures, while endoscopic bouginage is effective treatment of
      the strictures. To prevent recurrences esophageal bouginage should be combined
      with drug and laser therapy. The immediate response was reached in 91 (85%)
      patients. Long-term response was good only in 34 (46.6%) patients. Six slight
      complications passed off without special treatment.

PMID- 7725577
TI  - [Acoustic and radiologic analysis of speech formation in patients with laryngeal
      cancer before and after total laryngectomy with tracheoesophageal shunting and
      prosthesis].

PMID- 7725579
TI  - [Respiratory tract and immune status in patients with saturnism].

PMID- 7725580
TI  - [Cytologic analysis of benign neoplasms and some pseudotumors of
      otorhinolaryngologic organs].
AB  - The authors detail cytological picture of some benign tumors and pseudotumors
      encountered in otorhinolaryngological practice: oncocytoma, angioma, lipoma, soft
      fibroma, mixoma, paraganglioma, chondroma, angiogranuloma, cholesteatoma of the
      ear, protein pseudotumors (early-stage fibrinoid-hyaline nodes), polyps of the
      nose and ear, sarcoidosis. Cytological techniques made it possible to establish
      accurate diagnosis in 90% and 82% of cases with benign tumors and pseudotumors,
      respectively.

PMID- 7725578
TI  - [Sinus-catheter "Iamik" in the treatment of combined forms of acute suppurative
      sinusitis].
AB  - The efficacy of "YAMIK" sinus catheter versus conventional sinus punctures has
      been tried in acute purulent polysinusitis. "YAMIK" provides atraumatic
      evacuation of the discharge from all the sinuses on one side as well as
      introduction of the drugs into the sinuses via natural shunts by means of
      controlled intermittent pressure produced in the nasal cavity and paranasal
      sinuses. The methods was tested in 101 patients with acute purulent polysinusitis
      versus punctures of the maxillary and frontal sinuses in 30 controls. The
      differences in the outcomes were insignificant, through the catheter has the
      advantage of more rapid sinus cleansing. The authors recommend the above
      catheterization as pathogenetic, usable in inpatient and outpatient settings.

PMID- 7725581
TI  - [Effectiveness of low-frequency ultrasound in the treatment of chronic
      tonsillitis].
AB  - 500 patients with chronic tonsillitis (450 patients with toxicoallergic form I
      and 50 patients with toxico-allergic form II according to Palchun and
      Preobrazhensky) have been exposed to low-frequency ultrasound. Content of the
      tonsillar lacunae was extracted under vacuum, the lacunae were washed with
      antiseptic under the effect of ultrasound followed by introduction of the drugs
      into the tonsillar tissue (phonophoresis). The above method proved effective: 64%
      responded immediately, 56% of the patients sustained the effect at follow-up. Low
      frequency ultrasound treatment should be supported with therapeutic measures to
      prevent development of autoimmune processes capable of provoking systemic
      complications. For patients who failed 3-4 courses of the ultrasound treatment
      surgery is indicated. Contraindications concern subjects suffering from toxico
      allergic form II of chronic tonsillitis.

PMID- 7725582
TI  - [Surgical methods in the treatment of peritonsillitis].
AB  - The authors summarize the experience gained in paratonsillitis treatment
      conducted in the ENT clinic of Minsk Medical College for 1992-1993. The
      preference is given to surgical policy. The results of the treatment evidence for
      better tonsillectomy outcomes in warm seasons of the year.

PMID- 7725583
TI  - [Oropharyngeal resection in stage III cancer].
AB  - The oral part of the pharynx affected by cancer is subject to radiation, surgical
      and combined treatment. In stage IIIb the author practices resection of the oral
      pharynx by means of posterolateral pharyngotomy. This provides an adequate
      approach to the lesion area (the root of the tongue, vallecules, posterior and
      lateral walls of the pharynx) to perform ablastic resection of the oral pharynx
      with radical dissection of cervical fat.

PMID- 7725584
TI  - [Unilateral laryngeal paresis as an early symptom of recurrent nerve compression
      caused by tumor or trauma].
AB  - Out of 19 patients with unilateral laryngeal paresis, 8 patients developed the
      paresis early after strumectomy, 4 had lung tumors, 2 tumors of the esophagus, 2
      stab cervical wounds, 2 aortal arch dilatation, 1 patient had retrosternal
      goiter. Peripheral paralysis of the recurrent nerve is caused most frequently by
      the nerve compression in the thoracic cavity. The disease may be diagnosed
      accurately by ascertaining the causes underlying the nerve compression in the
      thoracic cavity using x-ray, ultrasound and computed tomography. Early diagnosis
      of mediastinal and pulmonary tumors enable conservative surgery with good
      functional results.

PMID- 7725585
TI  - [Ultraviolet irradiation of blood in acute sinusitis].

PMID- 7725586
TI  - [Audiometry in the diagnosis of cerebral ischemia complicated with acute
      subarachnoidal hemorrhage].
AB  - Hearing investigations (speech, tuning fork, pure-tone threshold audiometry) were
      conducted in 35 patients (18 males and 17 females aged 30-55) with acute
      subarachnoidal hemorrhage (ASH) which was spontaneous in 16 and resultant from
      rupture of the arterial aneurysm in 19 patients. Angiography registered in them
      local (11 patients), regional (14 patients) and diffuse (10 patients) spasm of
      cerebral vessels. Speech and tuning fork testing proved no hearing loss. Pure
      tone audiometry, on the contrary, revealed bilateral or symmetrical (in 91% and
      71% of the examinees, respectively) hearing loss in the majority of the patients
      (95.5%). Low-frequency and medium-frequency tones were received at slightly
      higher thresholds (20-25 dB). These thresholds were virtually similar in all the
      patients irrespective of the spasm severity and site. High-frequency sounds,
      especially 8000 Hz, were received inadequately almost by all the test subjects,
      the hearing thresholds being related to vasospasm severity, spread and location.
      These were 17-31 dB, 35-52 dB, 35-60 dB, 42-70 dB in patients with compensated
      and local arterial spasm, subcompensated and regional spasm, decompensated and
      diffuse spasm, basilar artery spasm, respectively. Pure-tone threshold audiometry
      can provide the basis for evaluating the severity, spreading and location of
      arterial spasm in ASH in acute phase and is recommended for examination of the
      above patients.

PMID- 7725587
TI  - [Surgical and microsurgical treatment of middle cysts and fistulas of the neck].
AB  - The paper presents the results obtained at the treatment of middle neck cysts and
      fistulas. Introduction of the surgical microscope contributed to radical
      dissection of the fistula passages which prevented the disease recurrences.

PMID- 7725588
TI  - [Lymphosarcoma of the papillary region invading the external acoustic meatus].

PMID- 7725589
TI  - [Generalized tuberculosis of the middle ear in newborn].

PMID- 7725590
TI  - [Sarcoidosis of the upper respiratory airways and ear].

PMID- 7725591
TI  - [Correction of immunologic disorders in patients with chronic suppurative otitis
      media].
AB  - The absolute and relative content of T- and B-lymphocytes, T-helpers (CD4), T
      suppressors (CD8), phagocytosis, complement and immunoglobulins A, M, G in the
      blood serum was examined in patients with chronic purulent otitis media. The
      investigation also involved tests on immunological activity of tymoptin (T),
      sodium nucleinate (SN), prodigiosan (PR), the combination of SN with PR. 148
      patients aged 15-56 years were subdivided into 5 groups. In pretreatment
      immunological status of all the patients the count of T- and B-lymphocytes, T
      helpers, phagocytosis were reduced against increased counts of IgM and T
      suppressora. All the patients received similar conventional treatment with
      adjuvant SN (group 2), PR (group III), SN + PR (group 4), T (group 5). The
      conventional conservative and especially surgical treatment aggravated
      immunodeficiency. The adjuvant immunocorrectors potentiated the treatment effects
      which appeared to be most beneficial in group V followed by by groups IV, II and
      III in diminishing order.

PMID- 7725592
TI  - Morphologic changes in the nasal cavity associated with sialodacryoadenitis virus
      infection in the Wistar rat.
AB  - A sequential study of lesions of the nasal cavity associated with
      sialodacryoadenitis virus (SDAV) infection was made in the laboratory rat. Wistar
      rats were intranasally inoculated with approximately 10(3) TCID50 of the
      coronavirus SDAV. Transverse sections of four regions of the nasal cavity from
      inoculated and control animals were examined by light microscopy and
      immunohistochemistry at 2, 4, 6, 8, 10, and 14 days postinoculation (PI). Lesions
      were observed in the following regions of the upper respiratory tract:
      respiratory epithelium, transitional epithelium, olfactory epithelium,
      nasolacrimal duct, vomeronasal organ, and the submucosal glands of the nasal
      passages. In general, in structures lined by ciliated epithelial cells, there was
      focal to segmental necrosis with exfoliation of affected cells and
      polymorphonuclear cell infiltration during the acute stages, progressing to
      squamous metaplasia during the reparative stages. Repair in these regions was
      essentially complete by 14 days PI. In the olfactory epithelium and the
      vomeronasal organ, there was interstitial edema with necrosis and exfoliation of
      epithelial cells and minimal to moderate inflammatory cell response during the
      acute stages. Residual reparative lesions were still evident in the olfactory
      epithelium, the columnar epithelium and neuroepithelium of the vomeronasal organ,
      and the nasolacrimal duct at 14 days PI. Viral antigen was demonstrated by
      immunohistochemistry in all regions during the acute stages of the disease, with
      the exception of the vomeronasal organ. In view of these findings, infections of
      the respiratory tract with viruses such as SDAV could have significant effects on
      functions such as olfaction and chemoreception for > or = 2 weeks postexposure in
      this species.

PMID- 7725594
TI  - Experimental transmission of enzootic intranasal tumors of goats.
AB  - The successful experimental transmission of enzootic intranasal tumor (EIT) from
      goat to goat is described. Ten kids, less than 48 hours old, from a flock free of
      the disease and seronegative for ruminant lentiviruses were inoculated
      intranasally or intrasinusally with either nasal fluid from goats with naturally
      occurring EIT or EIT retrovirus concentrated from such fluids. EIT was induced in
      three kids after 12-24 months. The EIT retrovirus was demonstrated in tumor
      material from each of the three kids by western blotting and electron microscopy.
      All kids were seronegative for ruminant lentiviruses.

PMID- 7725593
TI  - Occurrence of keratoconjunctivitis apparently caused by Mycoplasma gallisepticum
      in layer chickens.
AB  - Natural cases of keratoconjunctivitis, apparently caused by Mycoplasma
      gallisepticum (MG), in layer chickens are described. The disease occurred in a
      commercial flock consisting of 36,000 pullets (Babcock), first appearing around
      30 days of age. Clinically, affected chickens showed unilateral or bilateral
      swelling of the facial skin and the eyelids, increased lacrimation, congestion of
      conjunctival vessels, and respiratory rales. Some of the severely affected
      chickens closed their eyes. The morbidity reached 27.8%, and it was estimated
      that approximately 10% died from reduced feed intake due to impaired vision. Ten
      70-day-old chickens with clinical diseases were examined for lesions. There was
      acute to subacute keratoconjunctivitis in all of the chickens, and some exhibited
      laryngitis. Adherence of mycoplasma organisms to epithelial cells of the
      conjunctiva, cornea, and larynx was frequently observed. These organisms had an
      ultrastructure characteristic of MG and showed a positive reaction with rabbit
      polyclonal antibodies against the S6 strain of MG by immunohistochemical
      analysis. MG was isolated from tissue homogenates of the eyelids and tracheas of
      the affected chickens. Many of the chickens had atrophic bursae, and infectious
      bursal disease virus antigens were detected in necrotic bursal follicles by
      immunostaining. Therefore, immunosuppression due to infectious bursal disease was
      implicated in the pathogenesis of keratoconjunctivitis in the present cases.

PMID- 7725595
TI  - Susceptibility of porcine ileal enterocytes to the cytotoxin of Serpulina
      hyodysenteriae and the resolution of the epithelial lesions: an electron
      microscopic study.
AB  - The cytotoxin from Serpulina hyodysenteriae was injected into ileal loops of
      eight germ-free pigs, and the effects on the villi were observed after 1, 3, and
      18 hours of exposure. The mature vacuolated villus enterocytes of the proximal
      part of the absorptive villi were most susceptible to the lethal effects of the
      cytotoxin and were extensively exfoliated. The enterocytes at the base of the
      villi, the goblet cells, and the follicle-associated epithelium of the dome
      villi, particularly the M cells, were less affected. As the enterocytes were
      shed, the villi progressively shortened and the basement membrane became
      extensively folded. The absorptive villi were markedly stunted at 3 hours, and
      flattened globlet cells predominated at the site of restitution of the lesion.
      The myofibroblasts were also damaged, apparently subsequent to the exfoliation of
      the enterocytes. There was no further damage at 18 hours. The absorptive villi
      were stunted and were devoid of the large interstitial spaces of the normal
      lamina propria; the enterocytes were generally columnar, and at the apex of each
      villus there was an accumulation of goblet cells. There was a preponderance of M
      cells at the apices of the dome villi. Restitution of the lesions was not as
      rapid as observed in in vitro systems. The changes observed indicated that as the
      proximal enterocytes of the absorptive villi were shed, the loss of hydrostatic
      forces in the lamina propria allowed the myofibroblasts to collapse the villi by
      progressively retracting the basement membrane. This reduced the surface area to
      be covered during restitution. Resolution of the lesions was still incomplete
      after 18 hours.

PMID- 7725597
TI  - Lung lesions induced by continuous- and pulsed-wave (diagnostic) ultrasound in
      mice, rabbits, and pigs.
AB  - These studies documented the presence or absence of macroscopic and microscopic
      intraparenchymal hemorrhage in individual lung lobes of mice, rabbits, and pigs
      exposed to continuous- and pulsed-wave (diagnostic) ultrasound; we described the
      character of and lesions associated with the hemorrhage and compared differences
      in the lesions among species and exposure conditions to investigate the
      pathogenic mechanisms and species differences associated with ultrasound-induced
      lung hemorrhage. In a series of three sequential interdependent studies, 312
      mice, 91 rabbits, and 74 pigs were divided at random into experimental groups and
      exposed to continuous-wave ultrasound (3 kHz modulated at 120 Hz) of acoustic
      pressure levels ranging from 0 to 490 kPa for 5, 10, or 20 minutes. In a fourth
      study, three mice, 43 rabbits, and six pigs were divided at random into
      experimental groups and exposed to pulsed-wave ultrasound (3- and 6-MHz center
      frequency) of peak rarefactional acoustic pressure levels ranging from 0 to 5.6
      MPa for 5 minutes. Macroscopic lesions induced by continuous- and pulsed-wave
      ultrasound consisted of dark red to black areas of hemorrhage that extended from
      visceral pleural surfaces into lung parenchyma. Hemorrhage appeared spatially
      related to the edges of lung lobes where pleura of dorsal and ventral surfaces
      met, occurred in specific lung lobes in all three species, and appeared
      anatomically related to lung that was closest to and in contiguous alignment with
      the ultrasound transducer and thus the path of the sound beam. Macroscopic
      lesions were similar in all species under all exposure conditions for both
      continuous- and pulsed-wave ultrasound; however, hemorrhage was not induced in
      pig lung exposed to pulsed-wave ultrasound at any peak rarefactional acoustic
      pressure level. Eighteen mice (145 kPa exposure pressure), 60 rabbits (145-460
      kPa exposure pressure), and 58 pigs (145-490 kPa exposure pressure) from study 3
      were used for microscopic evaluation of lung exposed to continuous-wave
      ultrasound; three mice (6 MHz; 2.9 and 5.4 MPa), 39 rabbits (3 and 6 MHz; 2.3-5.4
      MPa), and six pigs (3 and 6 MHz; 3.3, 5.4, and 5.6 MPa) from study 4 were used
      for microscopic evaluation of lung exposed to pulsed-wave ultrasound. Microscopic
      lesions and the character of hemorrhage induced by continuous-wave ultrasound
      were different from those induced by pulsed-wave ultrasound. Lesions induced by
      continuous-wave ultrasound under all exposure conditions were similar in all
      three species. Lesions induced by pulsed-wave ultrasound under all exposure
      conditions were similar in all three species.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7725596
TI  - Ultrastructural and histomorphometric evaluations of gallium nitrate on bone in
      nude mice bearing a canine adenocarcinoma (CAC-8) model of humoral hypercalcemia
      of malignancy.
AB  - Gallium is a group IIIa transition metal that lowers serum calcium by an unknown
      mechanism and has been utilized in the treatment of cancer-associated
      hypercalcemia. The purpose of this study was to histomorphometrically investigate
      the ultrastructural effects of gallium nitrate on osteoclasts and osteoblasts in
      trabecular bone of normal nude mice and nude mice with humoral hypercalcemia of
      malignancy. Two groups of normal nude mice (n = 7 and n = 8, respectively) and
      two groups of hypercalcemic nude mice (n = 9) bearing a serially transplantable
      canine adenocarcinoma (CAC-8) were treated with vehicle or gallium nitrate.
      Osteoclasts were hypertrophied in vehicle-treated tumor-bearing nude mice as
      compared with vehicle-treated nontumor-bearing nude mice. Osteoclasts from tumor
      bearing nude mice treated with gallium nitrate were significantly decreased in
      size and had fewer intracytoplasmic vesicles as compared with osteoclasts from
      vehicle-treated tumor-bearing nude mice. Degenerate osteoclasts, characterized by
      pyknotic nuclei and increased cytoplasmic vacuolation, were observed in both
      groups of gallium-treated nude mice. Osteoblasts from vehicle-treated tumor
      bearing nude mice were hypertrophied and had extensive lamellar arrays of rough
      endoplasmic reticulum as compared with osteoblasts from vehicle-treated nontumor
      bearing nude mice. Osteoblasts in gallium-treated nude mice (tumor-bearing and
      nontumor-bearing) were small and flattened with poorly developed cytoplasmic
      organelles. This investigation demonstrated that osteoclasts and osteoblasts in
      nude mice treated with gallium nitrate had ultrastructural evidence of decreased
      metabolic and functional activity. The results suggest that gallium nitrate
      lowers serum calcium by inhibiting osteoclastic bone resorption.

PMID- 7725598
TI  - Cutaneous lymphoma in a ferret (Mustela putorius furo).

PMID- 7725599
TI  - Naturally occurring Tyzzer's disease in a puppy.
AB  - A naturally occurring case of Tyzzer's disease due to infection with Bacillus
      piliformis in a wolf-dog hybrid resulted in widely disseminated lesions,
      including severe myocarditis, hepatitis, enterocolitis, intestinal leiomyositis,
      and adrenal cortical adenitis. Previously reported lesions for canine Tyzzer's
      disease have been limited to hepatic necrosis and a necrotizing enterocolitis.

PMID- 7725600
TI  - Intracranial lipoma in a laboratory rat.

PMID- 7725601
TI  - Local production of tumor necrosis factor-alpha in corynebacterial pulmonary
      lesions in sheep.
AB  - Corynebacterium pseudotuberculosis infection is a common cause of pyogranulomas
      in ovine lungs and often occurs as a dual infection with lentiviruses. This
      coinfection usually leads to the development of chronic pneumonia and cachexia
      that is similar to the clinical syndrome seen in human beings with AIDS-related
      pneumonias. Recent in vitro studies indicate that monokines such as tumor
      necrosis factor-alpha (TNF alpha) are induced by C. pseudotuberculosis,
      suggesting that TNF alpha is involved in the pathogenesis of corynebacterial
      lesions in vivo. To substantiate in vitro observations concerning bacterial
      induction of TNF alpha in ovine pulmonary macrophages, immunohistochemical
      labeling techniques were used in combination with in situ hybridization to
      identify TNF-producing cells in corynebacterial lesion sites in vivo. TNF alpha
      message and translation product were found in macrophages comprising
      pyogranulomas that were induced by naturally acquired and experimental pulmonary
      C. pseudotuberculosis infections.

PMID- 7725602
TI  - Congenital axonopathy in a brown Swiss calf.

PMID- 7725603
TI  - Identification of a spontaneous pleomorphic rhabdomyosarcoma in the thoracic and
      abdominal cavities of a female Wistar rat.

PMID- 7725604
TI  - Disseminated Rhizopus infection with ocular involvement in a calf.

PMID- 7725605
TI  - Concurrent central nervous system toxoplasmosis and simian immunodeficiency virus
      induced AIDS encephalomyelitis in a Barbary macaque (Macaca sylvana).

PMID- 7725606
TI  - Subcutaneous and hepatic myelolipomas in four exotic birds.

PMID- 7725607
TI  - Multihormonal pancreatic endocrine tumor in a European lynx (Lynx lynx).

PMID- 7725608
TI  - Granulosa cell tumor of the testis in a CD-1 mouse.

PMID- 7725609
TI  - Assessment of proliferative activity by anti-PCNA monoclonal antibodies in
      formalin-fixed, paraffin-embedded samples and correlation with mitotic index.

PMID- 7725611
TI  - Comparison of isolates of canine parvovirus by restriction enzyme analysis, and
      vaccine efficacy against field strains.
AB  - Canine parvovirus isolates from clinical cases of enteritis were obtained from
      the United Kingdom, Germany and the USA and differentiated by restriction enzyme
      analysis into three groups, namely CPV2, CPV2a and CPV2b. The three groups were
      readily identified by their HphI restriction profile. CPV2 was not prevalent in
      cases of canine parvovirus disease after 1986. Only two CPV2 strains (original
      type) were found among 110 strains isolated after 1980. In Europe the frequency
      of isolation of the CPV2a and CPV2b field strains was similar whereas in the USA
      the CPV2b strain predominated. Dogs inoculated with a vaccine strain were
      resistant to infection after challenge with UK isolates of CPV2a and CPV2b.

PMID- 7725610
TI  - Plasma cortisol as an indicator of stress due to capture and translocation in
      wildlife species.
AB  - Plasma cortisol concentrations were determined by radioimmunoassay in 712
      individual animals of 18 wildlife species after either physical or chemical
      restraint, tranquillisation or trauma, in order to define baseline values and to
      assess the possibility of using cortisol as an indicator of stress. The cortisol
      levels appeared to rise after capture in all the species examined except the Cape
      buffalo. On the basis of the plasma cortisol levels, chemical capture was less
      stressful than physical restraint. Animals which were tranquillised had lower
      than 'normal' cortisol levels, whereas animals that had suffered trauma or which
      died after they were captured had higher than normal cortisol levels.

PMID- 7725612
TI  - Tenotomy of the tibial insertion of the semitendinosus muscle of two horses with
      fibrotic myopathy.
AB  - Two horses with fibrotic myopathy of the semitendinosus muscle are described. The
      report deals with the aetiology, clinical signs and diagnosis of the condition,
      and discusses the different surgical techniques described in the literature.
      Tenotomies were performed on both horses. Excellent results were obtained in the
      horse in which only the semitendinosus muscle was affected, but in the horse in
      which the semimembranosus and gracilis muscles were also involved the results
      were less satisfactory.

PMID- 7725613
TI  - Aneurysm of the cranial mesenteric artery in a cow.
AB  - An exploratory laparotomy of a four-year-old red Holstein cow with signs of
      abdominal discomfort revealed a painful pulsating mass in the cranial part of the
      abdomen. The cow died suddenly. A post mortem examination showed that a ruptured
      aneurysm of the cranial mesenteric artery had been the cause of death.

PMID- 7725614
TI  - Pathological diagnoses in dogs with lymph node enlargement.

PMID- 7725615
TI  - Possible involvement of Planococcus halophilus in an outbreak of necrotic
      hepatitis in chickens.

PMID- 7725616
TI  - Failure of the single enterotomy technique to remove a linear intestinal foreign
      body from a cat.

PMID- 7725617
TI  - Somatic cell count campaign.

PMID- 7725618
TI  - Treponemal infection in wild hares.

PMID- 7725619
TI  - Black hair follicular dysplasia.

PMID- 7725620
TI  - Bovine osteodystrophies.

PMID- 7725621
TI  - Neosporosis-associated bovine abortion in Israel.

PMID- 7725622
TI  - Specific amplification of Sarcocystis cruzi DNA using a randomly primed
      polymerase chain reaction assay.
AB  - The polymerase chain reaction (PCR) method to randomly amplify polymorphic DNA
      (RAPD) was used to differentiate between Sarcocystis cruzi DNA and bovine DNA.
      This assay was also exploited to identify a S. cruzi DNA fragment which may be
      useful as a probe. Five primers ranging in length from 16 to 20 nucleotides were
      analyzed for their ability to direct the amplification of either bovine or
      parasite DNA fragments. Two primers, TGA and TGD, preferentially amplified bovine
      DNA in a mixture of S. cruzi and bovine DNA. The primers TGB and TGF each
      directed the amplification of S. cruzi DNA instead of bovine DNA. Assays using
      TGF and S. cruzi DNA resulted in the production of a unique 0.8 kilobase (kb) DNA
      fragment. This fragment was not amplified from two other closely related
      coccidian species, Toxoplasma gondii and Sarcocystis campestris. When the 0.8 kb
      DNA fragment was purified and used as a DNA probe, it only hybridized with DNA
      from S. cruzi. The results of this study indicate that this DNA fragment may be
      developed into a useful DNA probe for S. cruzi, and that the RAPD-PCR method may
      be successfully exploited for the rapid development of DNA probes for parasites
      and other organisms.

PMID- 7725623
TI  - Increased susceptibility of erythrocytes to in vitro peroxidation in acute
      Trypanosoma brucei infection of mice.
AB  - Trypanosoma brucei, Wamba strain, produced an acute infection in mice, and
      mortality was observed 2 days after the onset of parasitaemia which occurred 3-5
      days postinfection. Anaemia was observed in the tail blood of the survivors. When
      washed erythrocytes from the heart blood were incubated in physiological saline
      containing 1.5% hydrogen peroxide, the erythrocytes of the infected mice produced
      significantly greater amounts of by-products of lipid peroxidation (measured as
      thiobarbituric acid reactive substances) than the erythrocytes of the control
      mice. This observation suggested that the infected mice may have a reduced
      ability in the prevention of free radical mediated lipid peroxidation in the
      erythrocyte membrane. It is concluded that peroxidative injury to the
      erythrocytes may contribute to the pathogenesis of anaemia in trypanosomosis.

PMID- 7725624
TI  - Quantitative estimation of the level of exposure to gastrointestinal nematode
      infection in first-year calves.
AB  - In two experiments groups of calves were exposed to different levels and patterns
      of infection with Ostertagia spp. and Cooperia spp. The experimental design
      simulated the stereotypic pattern of herbage infestation, including a normal or a
      delayed midsummer increase, under conditions of set-stocking. The purpose of the
      experiments was to investigate the accuracy of egg counts, pepsinogen and gastrin
      values and antibody titres as estimators of the level of exposure to infection.
      Faecal egg counts significantly reflected levels of exposure during the first
      half of the simulated grazing season. Antibody titres and pepsinogen values
      reflected levels of exposure best during August and September, partly depending
      on the pattern and range of levels of exposure. Antibody titres against Cooperia
      spp. were particularly useful when levels of exposure to gastrointestinal
      nematode infection were low. Gastrin values were elevated only at high levels of
      exposure, which caused large weight gain reductions, in the later part of the
      simulated first grazing season. It is suggested that antibody titres and
      pepsinogen values can be used for prognostic diagnosis, indicating whether or not
      control measures should be taken. Both estimators of infection correlated
      significantly with the realised weight gain at the end of the simulated grazing
      season. Egg counts in the second month after the initial infection (turnout) also
      may be of significant value to support decisions concerning control measures.
      Comparisons with data from field trials and experiments conducted by others under
      various conditions suggested that the conclusions of the present experiments are
      also valid under field conditions. Furthermore, the results supported the
      conclusions drawn from previous field work, that levels of exposure are often
      very low on commercial farms in the Netherlands.

PMID- 7725625
TI  - Relative effect of temperature and moisture on the development of strongyle eggs
      to infective larvae in bovine pats in Argentina.
AB  - To determine the most efficient microclimatic factors in bovine faeces that could
      explain the rate of development of parasitic nematode species, experimental pats
      were deposited in three locations (sun, shade and laboratory) in central-west
      Argentina during summer, autumn and winter seasons. Faecal water content (FWC)
      and temperature inside the pats were recorded during the duration of the
      experimental periods. The mean temperature and minimal values of FWC explained
      54% of the variability of the rate of development of Haemonchus (third-stage
      larvae per 100 eggs) and mean maximal temperature and minimal FWC values were the
      two main factors regulating Cooperia development (R2 = 0.42). Rainfall was the
      third factor. No microclimatic component explained the development of Ostertagia
      in our experiments.

PMID- 7725626
TI  - Anthelmintic resistance in goats in peninsular Malaysia.
AB  - Ninety-six randomly selected farms, located throughout peninsular Malaysia, were
      surveyed for goat nematodes resistant to benzimidazoles (BZ). On 33 farms BZ
      resistance was demonstrated by means of an egg hatch assay. Haemonchus contortus
      was found to be the main species involved in anthelmintic resistance. There was a
      positive association between the frequency of anthelmintic treatments on a farm
      and the presence of benzimidazole resistance. To assess the value of the egg
      hatch assay, faecal egg count reduction (FECR) tests were also performed on 20
      farms. On six farms the LD50 of thiabendazole (TBZ) was less than 0.10 micrograms
      ml-1 and the FECR higher than 95% and on ten farms with an LD50 TBZ of over 0.10
      micrograms ml-1 a FECR of less than 95% was measured. On four farms the FECR was
      less than 95%, although the egg hatch assay showed LD50 TBZ values of less than
      0.10 micrograms ml-1 and on two of these three farms a controlled efficacy test
      confirmed the presence of BZ resistant H. contortus. From these results it can be
      concluded that the egg hatch assay underestimated the true incidence of
      benzimidazole resistance. Levamisole resistance was detected with a FECR test on
      two of ten farms investigated.

PMID- 7725627
TI  - Ivermectin resistant Haemonchus contortus in Louisiana lambs.
AB  - Fifteen weaned crossbred (Suffolk x Louisiana Native) lambs were treated with
      albendazole (10 mg kg-1) to remove existing nematode infections. They were
      inoculated with Haemonchus contortus infective larvae from a residual population
      surviving treatment with the oral formulation of ivermectin (0.2 mg kg-1). One
      group of five lambs remained untreated, another group of five was treated with
      the injectable formulation of ivermectin (0.2 mg kg-1), and a third group of five
      was treated with the oral formulation of ivermectin (0.2 mg kg-1). Subsequent to
      the treatments, there was essentially no difference in mean fecal egg count or
      mean number of H. contortus recovered at necropsy between the three groups.

PMID- 7725628
TI  - Analysis of leucocytes and lymphocyte subsets for different clinical stages of
      naturally acquired feline immunodeficiency virus infection.
AB  - We report alterations in leucocytes numbers and lymphocyte subset percentages,
      determined by flow cytometry, for three observed and previously defined clinical
      stages (asymptomatic carrier (AC), AIDS-related complex (ARC) and AIDS) of
      naturally occurring FIV infection. Unstaged FIV-positive cats had significantly
      lower numbers of total leucocytes (WCC) and neutrophils, lower percentages of
      PanT+ and CD4+, lower CD4:CD8 ratio and a higher percentage of B cells compared
      with unstaged FIV-negative cats. When FIV-positive cats were separated into
      clinical stages and compared with matched FIV-negative cats, AC FIV-positive cats
      had a significantly lower WCC, lower absolute numbers of neutrophils and
      lymphocytes, lower percentages of CD4+ and CD8+ cells, lower CD4:CD8 ratios and a
      higher percentage of B cells than healthy FIV-negative cats. ARC FIV-positive
      cats had lower percentages of PanT+ and CD4+ cells, lower CD4:CD8 ratios and
      higher percentages of B cells than matched FIV-negative cats. FIV-positive cats
      with AIDS had significantly lower percentages of CD4+ cells than matched FIV
      negative cats. Comparisons among the three observed clinical stages of FIV
      positive cats showed that AC FIV-positive cats had significantly lower WCC,
      significantly lower absolute numbers of neutrophils and a significantly lower
      percentage of CD8+ cells than ARC FIV-positive cats. AIDS FIV-positive cats had a
      significantly lower percentage of B cells than AC or ARC FIV-positive cats. FIV
      positive cats had a similar leucocyte response to illness as FIV-negative cats
      but had consistently lower percentages of CD4+ lymphocytes. Thus, in the staging
      of FIV, a rise in the percentage of CD8+ lymphocytes could be used to distinguish
      between AC and ARC and a fall in the percentage of B lymphocytes could
      distinguish AIDS from AC and ARC.

PMID- 7725629
TI  - Immunopathology of experimental Jembrana disease in Bali cattle.
AB  - Sequential immunohistochemical studies of the lymphoreticular responses of Bali
      cattle (Bos javanicus syn. Bos sondaicus) after inoculation with the Jembrana
      disease virus were carried out using the peroxidase-antiperoxidase test for
      immunoglobulin containing cell assessment and the indirect immunoperoxidase test
      for lymphocyte subset assessment. The prevalence of immunoglobulin G-containing
      cells declined during the acute phase of the disease but became significantly
      elevated during convalescence. This trend was consistent with serological
      responses previously observed using an enzyme linked immunosorbent assay.
      Temporary immunosuppression appeared to occur during the acute phase of the
      disease as indicated by a decrease in the immunoglobulin G-containing cells in
      the lymphoid organs and an observed decrease in the BoCD4/BoCD8 lymphocyte ratio
      in lymph node follicles.

PMID- 7725630
TI  - Syngeneic lysis of reticuloendotheliosis virus-transformed cell lines transfected
      with Marek's disease virus genes by virus-specific cytotoxic T cells.
AB  - Cell-mediated immune responses against Marek's disease virus (MDV) antigens were
      examined using reticuloendotheliosis virus (REV)-transformed cell lines of two
      haplotypes (B19B19 and B13B13). These cell lines were stably transfected with
      cloned fragments of MDV DNA resulting in the expression of the MDV-specific
      phosphoprotein pp38. Effector cells were obtained from P2a (B19B19) and S13
      (B13B13) chickens at 7 days post inoculation with REV, oncogenic or attenuated
      serotype 1 MDV (JM-16/O and JM-16/A, respectively), serotype 2 MDV (SB-1), or
      herpesvirus of turkeys (HVT). Transfection of MDV genes did not influence the
      expression of Class I major histocompatibility complex antigens. The optimal
      effector to target cell ratio was determined to be 100:1. REV-sensitized effector
      cells lysed REV cell lines and REV cell lines transfected with MDV DNA in a
      syngeneic fashion. Effector cells from chickens inoculated with JM-16/O, JM-16/A,
      SB-1 or HVT lysed only the syngeneic, transfected cell lines, but not the parent
      REV cell lines. The percentage specific release caused by the MDV-sensitized
      effector cells was low, but statistically significant.

PMID- 7725631
TI  - Genetic variation in the humoral immune response against Vibrio salmonicida and
      in antibody titre against Vibrio anguillarum and total IgM in Atlantic salmon
      (Salmo salar).
AB  - Total IgM level and antibody titre to Vibrio anguillarum O-antigen after bath
      vaccination, and specific antibody response to V. salmonicida O-antigen at three
      different samplings were analysed in family material of Atlantic salmon (Salmo
      salar), consisting of 791 fish belonging to 34 maternal full-sib groups within 12
      paternal half-sib groups. The fish were immunized twice, and blood samples
      collected three times. After the third blood sampling, the fish were challenged
      with V. anguillarum. Medium to low genetic variation was recorded in total IgM
      and in the antibody titres against V. anguillarum O-antigen and V. salmonicida O
      antigen, with heritability estimates of 0.12, 0.18 and from 0.03 to 0.12,
      respectively. Moderate to high genetic and phenotypic correlations were found
      between the V. salmonicida O-antigen titres at different samplings. Genetic and
      phenotypic correlations between the initial titres were moderate to low. The
      effect of different immune traits, including Aeromonas salmonicida A-layer titres
      (previously described), on the ability to survive the challenge was examined. The
      likelihood of surviving the challenge was affected positively by the A.
      salmonicida A-layer titre at the second sampling, and almost significantly
      affected by the initial V. anguillarum O-antigen titre. Production traits, such
      as mean slaughter weight and mean proportion of survivors in a corresponding full
      sib material, were obtained in the sea-rearing period. No significant full-sib
      correlation between immune parameters and production traits was detected.

PMID- 7725632
TI  - Detection of interleukin-6 and prostaglandin E2 in bronchoalveolar lavage fluids
      of pigs experimentally infected with Mycoplasma hyponeumoniae.
AB  - In this study, interleukin-6 (IL-6) and prostaglandin E2 (PGE2) were detected in
      the bronchoalveolar lavage fluids (BALF) from pigs experimentally infected with
      Mycoplasma hyopneumoniae. IL-6 was detected at 2 weeks post-inoculation (PI), and
      significantly increased levels of PGE2 were observed at 4 weeks PI. In the BALF
      collected from infected pigs at 4 weeks PI, the levels of IL-6 increased
      significantly in the pigs with pneumonic lesions. However, increased levels of
      PGE2 were observed in all the infected pigs.

PMID- 7725633
TI  - [Insulin resistance and hyperlipoproteinemia].
AB  - Insulin resistance is part of the so-called plurimetabolic syndrome where it was
      observed in association with various signs among which the association with
      impaired serum lipids is very frequent. The most frequent deviations are
      hypertriacylglycerolaemia (in particular VLDL), low HDL-cholesterol and elevated
      serum levels of non-esterified fatty acids. Some hitherto assembled findings
      suggest a close relationship between glucose and lipid metabolism. Enhanced
      oxidation of non-esterified fatty acids leads to inhibition of glucose oxidation
      and this may participate in the development of insulin resistance. Changes in
      cholesterol and triacylglycerol levels seem to be rather the consequence than
      cause of the development of insulin resistance. It cannot be ruled out that
      insulin resistance is genetically conditioned and this would explain the other
      associated changes as secondary ones.

PMID- 7725634
TI  - [Insulin resistance and arterial hypertension].
AB  - The hypothesis of insulin resistance in the pathogenesis of arterial hypertension
      as part of the hormonal metabolic X syndrome and our 5H syndrome resp.
      (association of hyperinzulinism with hyperglycaemia-NIDDM-hyperlipoproteinaemia,
      hypertension and a hyperandrogenic state in women) is based on sympathomimetic,
      sodium retention and trophic effects of insulin. In the submitted paper the
      authors review opinions supporting and refuting the validity of this hypothesis.
      Based on the results of different studies in recent years another genetic
      predisposition comes also to the foreground, i.e. reduced vascularization of the
      skeletal muscles which on the background of insulin resistance leads to enhanced
      development of hypertension with subsequent hypertrophy of the vascular wall and
      left ventricle and to the development of arteriosclerosis. From the clinical
      aspect this stimulating pathogenetic concept within the framework of the hormonal
      and metabolic X syndrome and 5H syndrome makes it possible to use a more adequate
      approach to prevention and treatment not only of arterial hypertension but also
      of associated phenomena which enhance the risk of cardiovascular morbidity and
      mortality in the population. The authors summarize factors which during non
      pharmacological treatment promote insulin resistance and those which improve it.
      When drugs are selected for pharmacological treatment, priority is given to those
      which improve the insulin sensitivity index (ACE-inhibitors, alpha blockers) or
      are at least neutral in this respect (Ca antagonists, beta blockers with ISA and
      cardioselective). The drugs must not enhance associated hyperlipoproteinaemia,
      hypercoagulability, hyperviscosity, hyperuricaemia) and they should exert a
      positive effect on the regression of hypertrophic vascular walls and the left
      ventricle.

PMID- 7725635
TI  - [Ischemic heart disease with significant coronary stenosis and insulin
      resistance].
AB  - The authors examined a group of 22 patients with significant stenoses revealed on
      coronarographic examination. None of the patients were diabetic.
      Hyperinsulinaemia was found in 12 patients (54.5%). The hyperinsulinaemic and
      normoinsulinaemic groups differed significantly as to the type of obesity
      expressed by the W/H ratio, the incidence of hypertension and triglyceride
      levels. The authors discuss the direct participation of insulin resistance and
      compensatory hyperinsulinism in the pathogenesis of atherosclerosis and its
      participation in the manifestation of associated risk factors (dyslipidaemia,
      hypertension, obesity and NIDDM).

PMID- 7725638
TI  - [Insulin resistance in kidney diseases].
AB  - Insulin resistance (IR) is found in different kidney diseases in almost half the
      patients with mild to medium severe disorders of renal functions; in advanced
      renal failure it is almost constant. In addition to pathogenetic mechanisms known
      in other diseases of Reaven's syndrome it has some specific features: Already in
      the early stages calcitriol production is impaired, and if the calcium intake is
      not increased and calcitriol is not substituted, secondary hyperparathyroidism
      with osteodystrophy develops. The intracellular concentration of free Ca
      increases and the intracellular concentration of free Mg declines. Activation of
      the renin angiotensin system (RAS) stimulates Ca release from intracellular
      reserves and potentiates thus the cumulation of free Ca in the cytoplasm.
      Magnesium plays a special part as it influences glucose utilization by several
      mechanisms. Diagnosis, prevention and therapy of IR are an essential part of
      comprehensive prevention of progressing nephropathies with a predicted decline of
      patients requiring dialysis by cca 30% by the year 2000. This calls, however, for
      concentrated efforts of all health professionals.

PMID- 7725637
TI  - [Hyperandrogenic states in women (polycystic ovary syndrome) and insulin
      resistance].
AB  - In the submitted paper the authors try to explain the relationship between
      hyperinsulinism as the cause and the polycystic ovary syndrome as the consequence
      of hyperinsulinism. This takes place via the insulin like growth factor I, the
      luteinizing hormone, sex binding hormone globulin, insulin like growth factor I
      binding protein and growth hormone. By varying interactions of the regulatory
      hormones gradually the granulosa cells are destroyed and replaced by
      androstendione producing thecal and stromal cells with impaired folliculogenesis.
      Chronic hyperestrogenism interferes also with hypothalamic regulation in the
      nucleus arcuatus. As almost identical changes are found in polycystic ovary
      syndrome and puberty, genetic and/or environmental factors certainly play a part.
      Their more detailed specification is a task for the future.

PMID- 7725636
TI  - [Microvascular angina pectoris and insulin resistance].
AB  - The authors examined 29 patients with the syndrome of microvascular angina
      pectoris. In 12 patients (41.4%) they recorded hyperinsulinaemia as a
      manifestation of insulin resistance. The body weight, HDL cholesterol level, LDL
      cholesterol and triglycerides did not differ significantly in the two groups and
      were at the upper borderline of the range of reference values. The authors
      analyze mechanisms common to the pathophysiology of the syndrome of microvascular
      angina pectoris and the syndrome of insulin resistance.

PMID- 7725639
TI  - [The importance of diet therapy in the prevention and treatment of manifestations
      of metabolic syndrome X].
AB  - The authors present an account of dietetic principles in the treatment of the
      metabolic syndrome X (Reaven 1988). Principles valid til recently are compared
      with the most recent views based on experimental and clinical investigations,
      using molecular methods. The authors explain in detail the importance of
      monounsaturated and polyunsaturated fatty acids in the oil of marine fish which
      are important not only for reducing the blood lipid level but also to improve the
      insulin resistance and they reduce slightly the blood pressure.

PMID- 7725641
TI  - [Anti-insulin antibodies and insulin resistance].
AB  - The submitted review deals with the phenomenon of immunological insulin
      resistance in insulin dependent diabetics which develops as a result of the
      presence of circulating anti-insulin antibodies as a response of the organism to
      administered insulin. This phenomenon is a liminal situation when anti-insulin
      antibodies exceed as to their concentration and affinity a certain arbitrary
      limit and the increasingly impaired pharmacokinetics of insulin cause a
      clinically manifest metabolic decompensation of the disease with the necessity of
      large daily doses of exogenous insulin. The authors discuss factors ensuing from
      the type of the administered insulin preparation, as well as the biological
      predisposition of the patient which potentiates the production of anti-insulin
      antibodies. Some laboratory methods are discussed which are used for the
      assessment of anti-insulin antibodies in vitro and the authors summarize
      individual physical variables which characterize the antibody system and which
      can be extracted by special mathematical procedures from experimental
      radioimmunoanalytical data. Only a detailed characterization of the antibody
      system makes it possible to evaluate the influence of this system on the
      pharmacokinetics of insulin.

PMID- 7725640
TI  - [Insulin resistance and combined therapy with sulfonylurea and insulin in non
      insulin dependent diabetics].
AB  - The author explains the mechanisms of insulin resistance and impaired insulin
      secretion which are the main signs in the pathogenesis of non-insulin-dependent
      diabetics. Both reasons are the basis of secondary failure of sulphonylurea
      treatment or the necessity to administer large doses of insulin to achieve a
      normal blood sugar level in these patients. By combined treatment, i.e. by adding
      small amounts of insulin to the original treatment with sulphonylurea
      antidiabetics or by adding sulphonylurea to large insulin doses, it is possible
      to compensate the patient as effectively as with insulin treatment alone. The
      author analyzes the procedure of changing over to combined treatment which should
      be implemented during hospitalization of the patient. Finally the author
      evaluates the effect of combined treatment from data in the literature as well as
      his own experience which indicate that to achieve equal metabolic compensation
      combined treatment with sulphonylurea and insulin requires substantially lower
      insulin doses, as compared with insulin treatment only.

PMID- 7725642
TI  - [Patient education in the metabolic syndrome].
AB  - In the treatment of the metabolic syndrome which comprises the most serious risk
      factors of atherosclerosis education is a basic prerequisite of treatment and
      prevention of complications. In the submitted review the authors analyze basic
      procedures of education from the general aspect as well as in individual
      disorders and diseases which characterize the metabolic syndrome
      (dyslipoproteinaemia, obesity, diabetes mellitus and impaired glucose tolerance,
      hypertension). They emphasize that a comprehensive change of the patient's life
      style and the life style of his whole family is necessary. This cannot be
      achieved within a short time and therefore motivation of the patient as well as
      of the health professionals engaged in the educational work is essential.

PMID- 7725643
TI  - [The insulin resistance syndrome].

PMID- 7725644
TI  - [Cellular and molecular mechanisms of insulin resistance].
AB  - In the submitted review the authors give an account of contemporary knowledge
      regarding the mechanism of insulin action, including a brief account of
      pathological conditions associated with insulin resistance. The development of
      knowledge of problems of insulin resistance syndromes was always very dynamic,
      and due to the introduction of techniques of molecular biology and genetics at
      the turn of the eighties and nineties, a further very marked step forward was
      made. Despite this it will take some time before molecular mechanisms which will
      confirm (or rule out?) the etiopathogenetic importance of insulin resistance not
      only for diabetes but also for hypertension, dyslipidaemia, IHD will be revealed.

PMID- 7725645
TI  - [Review of in vivo technics in the quantification of insulin sensitivity].
AB  - The ability to measure insulin sensitivity plays important role mainly in
      investigation of pathogenesis of noninsulin-dependent diabetes mellitus. The
      measurement of insulin sensitivity means to measure the insulin's effect on
      glucose metabolism--on hepatic glucose production and peripheral glucose uptake.
      From all in vivo techniques for measurement of insulin sensitivity are considered
      for most suitable at the present time next 2: clamp technique (euglycemic
      hyperinsulinemic and hyperglycemic hyperinsulinemic clamp) and Bergman's minimal
      model technique. Clamp methods and minimal model method are significantly
      correlated in vivo methods for measurement of insulin sensitivity and beta-cell
      secretory function as well.

PMID- 7725646
TI  - [Clinical manifestations of the insulin resistance syndrome. The hormonal
      metabolic syndrome X, the 5H syndrome and their etiopathogenesis].
AB  - The author summarizes mechanisms by which insulin resistance and compensatory
      hyperinsulinism are manifested in the clinical picture. He divides the mechanisms
      into prereceptor, receptor and postreceptor mechanisms. The latter dominate in
      the population quantitatively and thus also by their impact because they create
      the so-called 5H syndrome (association of hyperinsulinism with hyperglycaemia
      (NIDDM), hyperlipoproteinaemia, hypertension, hirsutism and the polycystic ovary
      syndrome) or the so-called hormonal metabolic syndrome X, lethal tetrad,
      metabolic syndrome, syndrome of insulin resistance). The term syndrome X does not
      appear suitable as it is frequently mistaken for coronary X syndrome which
      probably is also conditioned by hyperinsulinism, for the hormonal metabolic X
      syndrome and probably also fot the "fragile X syndrome" in genetics. The 5H
      syndrome is caused by a postreceptor disorder of insulin efficiency for which so
      far the molecular basis and dominating organ site have not yet been defined
      adequately. Hyperinsulinism is conceived as an insulin resistance compensating
      phenomenon. In its development participates, however, in addition to compensatory
      hypersecretion also impaired insulin utilization (liver, muscles) and an impaired
      primary secretory response caused probably by a disorder of blood sugar control
      (glucokinase, GLUT 2). This is suggested by the frequently inadequate response of
      the blood sugar level, IRI and C-peptide during the oral glucose tolerance test
      (OGGT). A hyperinsulinaemic response may be encountered when the blood sugar
      curve is normal, flat, in impaired glucose tolerance and in diabetes. Thus OGGT
      alone is not suited for the early detection of the 5H syndrome unless
      concurrently the IRI and C-peptide response is recorded.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7725647
TI  - [Insulin resistance and non-insulin dependent diabetes mellitus].
AB  - Normal glucose tolerance depends primarily on 1) the ability of the body to
      secrete insulin, 2) the normal insulin action in target tissues, it means the
      ability of insulin to inhibit hepatic glucose production and to promote glucose
      uptake, 3) and the ability of glucose to enter the cells in the absence of
      insulin. Clinically overt non-insulin-dependent diabetes mellitus (NIDDM) is
      characterized by abnormality of insulin secretion combined with insulin
      resistance in glucose metabolism of all major target tissues. While the fasting
      hyperglycaemia depends primarily on decreased insulin ability to inhibit hepatic
      glucose production, in the postabsorptive state the main role is played by
      decreased insulin-stimulated glucose uptake in muscles and impaired glycogen
      synthesis. Because of hyperglycaemia, and increased insulin-independent glucose
      uptake, whole glucose utilisation is not altered in NIDDM. Combination of genetic
      and environmental factors leading to secondary changes in insulin action,
      contribute to the pathogenesis of insulin resistance and progression of NIDDM.

PMID- 7725650
TI  - [Let us do everything for the fastest recovery of victims. Interview by G. G.
      Piskunov].

PMID- 7725648
TI  - [Current problems in organizing therapeutic care].
AB  - The article studies the problems in organization of therapeutical care in Mobile
      Forces on the basis of the analysis of medical support of troops in local wars.
      The authors emphasize the high dynamics of changes in the structure of military
      disease hazards depending on different combat theaters. This fact proves the
      necessity to make a transition to a module principle of formation of medical
      units and establishments which provide medical care to the wounded and sick.

PMID- 7725649
TI  - [The organization of qualified and specialized medical care for light casualties
      and the mildly ill requiring therapy].

PMID- 7725651
TI  - [The diagnosis and surgical procedure in chest trauma].

PMID- 7725652
TI  - [The control of acute blood loss at the advanced stages of medical evacuation].

PMID- 7725653
TI  - [Variants in using the tubed pedicle in restorative operations on the face and
      the organs of the oral cavity].
AB  - This article is based on 83 histories (89% male, 11% female) of patients who were
      operated for penetrating or superficial maxillofacial defects and deformations.
      293 step-by-step operations were conducted using the bucket-handle graft in
      combination with nearest tissues. Age of patients: from 18 to 65. The Filatov
      Gillies tubed pedicle was used as a carrier for hair-covering chin grafts which
      were implanted into de-epidermized zones during the formation of eyebrows in
      supraorbital areas. Bucket-handle graft was also used for reconstruction of lips,
      including vermillion border. The article contains the history and a photo of a
      woman who was operated for basaloma of nose and upper lip. After the destruction
      of a new growth by cryogenic method the plasty of upper lip and vermillion border
      was carried out with the help of one Filatov-Gillies tubed pedicle. The healing
      of wounds have proceeded without complications in 93.9 +/- 1.4% of cases. In 2
      patients a partial necrosis of graft took place. One graft was removed. The
      divergence of stitches was marked in 15 (18%) of patients. Nevertheless it did
      not influence upon the outcome of reconstructive treatment.

PMID- 7725654
TI  - [Loyalty to professional and military duty].
AB  - The author of this article--Chief of the Russian Armed Forces Medical Service-
      analyses the trends of optimization of medical support of the Army and Navy,
      taking into account the experience of combat casualty care during Chechen crisis.
      In order to enhance the efficiency of medical support during combat activities
      all the personnel is supplied with first-aid kits. Each company is reinforced
      with a medical assistant or army physician; battalion medical posts--with
      physicians, medical assistants, aidmen, mobile dressing room and ambulances;
      regiment medical posts--with two surgeons, an anaesthesiologist, an instrument
      nurse and nurse-anaesthetist. The primary medical care is provided at the
      battalion medical post; qualified (secondary) surgical care--at regiment medical
      posts, and specialized (tertiary) medical care--at special medical detachments
      (SMD) and military hospitals. The wounded are evacuated from the zone of combat
      actions by APC or MICV, and then by helicopters. The further evacuation of
      wounded is realized by transport or medical aircraft, including "Skalpel" flight
      surgery plane. The experience of army physicians has proved the necessity of
      multilateral development of Mobile Forces Medical Service and the formation of
      aeromobile hospitals. An airborne infantry battalion must have a medical company
      in its organic structure, and respectively a separate medical battalion must have
      an aeromobile medical company. The SMD which are assigned to act in the emergency
      situations of peaceful time also can be effective in providing medical care
      (including specialized care) during local military conflicts. Thinking over the
      further development of medical support in the Armed Forces the author assigns a
      number of tasks throughout all the chain of medical command, including medical
      establishments, medical examination boards, the Corps of Senior medical
      specialists (in surgery, internal medicine, pathologicoanatomy, sanitary
      supervision, etc). A special attention is paid to the formation of an efficient
      system of sanitary-epidemiological supervision in the Armed Forces; the
      improvement of medical assistance for servicewomen, retired officers and their
      dependents; the enforcement of military and labour discipline in the units and
      establishments of medical service; training and education of medical personnel;
      the strict adherence to the principles of medical ethics, deontology, and oath of
      physician.

PMID- 7725655
TI  - [Acute pneumonia as a problem of hospital infection].
AB  - The article is about an acute pneumonia which develops in weak patients in
      nosocomial conditions. The authors study the question of secondary pneumonia, its
      etiology, systematization, diagnosis and treatment including application of
      immunocorrectors.

PMID- 7725656
TI  - [The concept of epidemiological health well-being in the Armed Forces].

PMID- 7725657
TI  - [The assessment and prognosis of body functional states in servicemen].

PMID- 7725658
TI  - [Enhancement of the fixation potentials of the Dietrich splint].

PMID- 7725659
TI  - [A universal transport splint for the extremities].

PMID- 7725660
TI  - [The organization of medical support for the troops in the Vistula-Oder Offensive
      Operation].

PMID- 7725661
TI  - [The chief infectious disease specialist of the Red Army (on the centenary of the
      birth of I. D. Ionin)].

PMID- 7725662
TI  - [Mil'tiad Ivanovich Teodori (on the 90th anniversary of his birth)].

PMID- 7725663
TI  - [Aleksei Epifanovich Kurashvili (on the 80th anniversary of his birth)].

PMID- 7725664
TI  - [The characteristics of the organization of hospital and outpatient polyclinic
      care abroad (a review of the literature)].

PMID- 7725665
TI  - [The contribution of aviation medicine to military science and practice (on the
      60th anniversary of the State Research Experimental Institute of Aviation and
      Space Medicine of the Ministry of Defense of the Russian Federation)].

PMID- 7725667
TI  - Blood exchange [correction of exchance]-a rescue procedure for complicated
      falciparum malaria.
AB  - Falciparum malaria is the most hazardous form of malaria. Its high degree of
      parasitemia interferes with vital functions of most organs and is directly
      responsible for its high rate of mortality and morbidity. Quinine and other
      antimalarial drugs are relatively slow acting and not always effective due to the
      growing resistance developed by Plasmodium toward these drugs. Another emergency
      modality, which would remove the parasitic burden quickly and effectively, is
      thus much needed. We present a case of a 51-year-old sailor, who was admitted to
      the hospital because of complicated falciparum malaria. His situation
      deteriorated rapidly into a desparate stage, despite the various intensive
      treatments and quinine. He soon developed a systemic inflammatory response
      syndrome manifested as cerebral malaria, renal failure, acute respiratory
      distress syndrome and disseminated intravascular coagulation. An emergency blood
      exchange reversed the situation dramatically, and the patient recovered
      completely. It is recommended that any doctor, both in endemic and in non endemic
      areas, dealing with blood transfusions or infectious diseases, should be
      acquainted with this lifesaving modality, regardless of the controversy still
      surrounding this subject.

PMID- 7725666
TI  - Thermal stability of human immunoglobulins with sorbitol. A critical evaluation.
AB  - The effect of the additive sorbitol on the thermal stabilization of human IgG was
      investigated by differential scanning calorimetry and size exclusion
      chromatography. In the presence of 33% sorbitol, the temperature at which
      denaturation of IgG began (Ti) was increased from 52 to 65 degrees C. Similarly,
      the temperature of the maximum heat capacity (Tmax) was increased from 69 to 76
      degrees C. Sorbitol also decreased dimer aggregation and the extent of
      oligomerization during heating compared with IgG dissolved in phosphate buffer.
      Sorbitol at 33% prevented massive protein denaturation but a 10-15% of
      oligomerization of high molecular weight aggregates with turbidity could not be
      avoided when heating for 10 h at 60 degrees C. The use of sorbitol 33% to avoid
      heat denaturation of human IgG during viral inactivation did not prevent protein
      aggregation or the appearance of turbidity. Consequently, further processing will
      be required to achieve a product suitable for pharmaceutical use.

PMID- 7725668
TI  - A solid-phase test using antiglobulin and enzyme-enhanced techniques for
      erythrocyte antibody screening during pregnancy.
AB  - We have modified previously described solid-phase tests for erythrocyte antibody
      screening to develop a method, suitable for antiglobulin- and enzyme-enhanced
      techniques (SPH-IAT and SPH-ENZ). In this study we compared the SPH tests with an
      autoanalyzer (AA) technique. The results were more specific with the SPH tests
      than with the AA. Of 4,234 unselected samples from pregnant women, screen
      positive samples were reduced from 96 (2.27%) by the AA, to 56 (1.32%) by the SPH
      tests. This difference was due to the reduced number of false-positive reactions
      with the SPH tests, 0.47% compared to 1.44% with the AA. Antibodies detected by
      the AA and the SPH-IAT and -ENZ were: 9 Rh prophylaxis, 2 anti-c, 1 anti-K and
      anti-M, and 1 anti-Jka. Antibodies detected only by the SPH tests were 1 anti-K,
      1 anti-Le(a) (SPH-IAT and -ENZ), 1 anti-M (SPH-IAT) and 4 anti-Jka (SPH-ENZ). One
      anti-C, 2 anti-D, 3 Rh prophylaxis and 1 anti-E were detected by the AA and the
      SPH-ENZ but failed to react by the SPH-IAT. One anti-Le(a) and 8 Rh prophylaxis
      antibodies were detected by AA only. All clinically important antibodies were
      detected by the SPH tests. We conclude that the SPH-IAT and SPH-ENZ are screening
      methods with high specificity that are readily adaptable to larger series of
      samples from pregnant women and suitable for automated handling throughout the
      screening and identification process.

PMID- 7725669
TI  - Incidence and diagnosis of EDTA-dependent pseudothrombocytopenia in a consecutive
      outpatient population referred for isolated thrombocytopenia.
AB  - Among 111 patients referred to our outpatient clinic for isolated
      thrombocytopenia during a 24-month period, 17 (15.3%) cases of EDTA-dependent
      pseudothrombocytopenia (EDTA-PTCP) were identified. EDTA-PTCP represented the
      second most frequent cause of thrombocytopenia in this population. The diagnosis
      was confirmed by the following findings: (a) normal platelet numbers immediately
      after blood withdrawal; (b) progressive fall of platelet counts and evident
      platelet clumping over time, only in EDTA-anticoagulated blood. A simple,
      inexpensive and quick diagnostic method was devised, that consists in evaluating
      the platelet number in a blood sample anticoagulated with EDTA immediately after
      blood withdrawal and 4 h later.

PMID- 7725671
TI  - Pharmacokinetics of single and multiple infusions of 5S intravenous
      immunoglobulin.
AB  - A prospective, open and uncontrolled trial was performed to investigate the
      pharmacokinetics of a 5S intravenous immunoglobulin (IVIG) after single and
      multiple infusions. Twelve healthy volunteers received a 5S-IVIG enriched in
      antibodies against Staphylococcus aureus alpha-toxin (aSAT) either as a single
      infusion or as three infusions in daily intervals. The fate of the injected
      immunoglobulin was observed by serial measurements of the serum level of aSAT
      titres. The 5S-IVIG had a half-life with a median of 0.24 (distribution) and 2.0
      (terminal) days, respectively. The pharmacokinetic parameters did not differ with
      dose groups or number of applications. The study medication was well tolerated.

PMID- 7725670
TI  - K12 is located on the Kell blood group protein in proximity to K/k and Jsa/Jsb.
AB  - K12 is a high-prevalence antigen, with no known antithetical partner, that is
      associated with the Kell blood group system. We report studies on the 5th
      propositus (MS) with the K:-12 phenotype and the second case to show that the K12
      is inherited. The anti-K12 in his serum did not destroy antigen-positive
      incompatible red cells transfused on at least 3 occasions over 6 years. Red cell
      membranes from MS possessed the Kell protein that was indistinguishable from
      control membranes. K12 antigen was shown by immunoprecipitation to be on a
      protein with an apparent molecular mass of 93,000 and by monoclonal antibody
      immobilization of erythrocyte antigens (MAIEA) assay to be on the Kell protein in
      proximity to K/k and Jsa/Jsb antigens. These data remove the K:-12 phenotype from
      its current Kell-related (or para Kell) status and elevates the K12 antigen to a
      bona fide member of the Kell blood group system.

PMID- 7725672
TI  - Characterization of mutants of the vitamin-D-binding protein/group specific
      component: GC aborigine (1A1) from Australian aborigines and South African
      blacks, and 2A9 from south Germany.
AB  - The structure and organization of the human vitamin-D-binding protein gene (DBP,
      group-specific component, GC) have recently been determined. Each exon may now be
      amplified by the PCR method using oligonucleotide primers deduced from the intron
      sequences near their 5' ends and 3' ends. In this study we examined the anodal GC
      variants 1A1 and 2A9. Genomic DNA of the variant 1A1 was obtained from Australian
      Aborigines and from South African Bantu-speaking Blacks. Amplification and
      sequencing of exon 11 of 1A1 revealed a point mutation in codon 429 at the second
      position. It is remarkable that this mutation was found in the Australian 1A1
      variant and in the African 1A1 variant, and raises the question whether the
      mutation in these two ethnic groups has a common origin. Genomic DNA of the 2A
      variant called 2A9 was obtained from South Germany and a point mutation also
      concerning position 429 in exon 11 was found. The nucleotide exchange in this
      case, however, was at the first position of the codon. The widely distributed
      genetic polymorphism of DBP/GC is located in exon 11 and is characterized by
      substitution at amino acid positions 416 and 420. Variant 1A1 is due to a second
      site mutation of the allele GC*1F; variant 2A9 is due to a mutation in the GC*2
      allele.

PMID- 7725674
TI  - Severe heat treatment of freeze-dried coagulation factor concentrates: is hotter
      necessarily better?

PMID- 7725673
TI  - Toxic shock syndrome after staphylococcal pneumonia treated with intravenous
      immunoglobulin.

PMID- 7725675
TI  - Prevalence of antibodies to HTLV-I/II in high-risk patients and blood donors in
      Denmark.

PMID- 7725676
TI  - Clinically significant anti-LWab by monocyte monolayer assay.

PMID- 7725677
TI  - Lewis phenotypes in Orientals.

PMID- 7725678
TI  - Human cytomegalovirus DNA is not detectable with nested double polymerase chain
      reaction in healthy blood donors.
AB  - The PCR method was introduced to detect cytomegalovirus (CMV) DNA from 189
      peripheral blood samples of volunteer donors. We adopted the nested double PCR
      method with primers specific for immediate early gene 1 followed by
      electrophoresis and ethidium bromide staining. This nested double PCR method was
      sensitive enough to detect approximately a single copy of CMV DNA. However, we
      failed to obtain positive amplification of CMV DNA from any of these donor
      samples. In contrast, CMV DNA could be detected in all 3 tested immunocompromised
      patients who had undergone bone marrow transplantation. These results support our
      previous report that the frequency of CMV DNA is of an order lower than 1
      copy/10(5) leucocytes in the peripheral blood of healthy seropositive
      individuals.

PMID- 7725679
TI  - [A new zoonosis--investigation of Gardnerella vaginalis disease of fox. I.
      Causative agent isolation and artificial infection].
AB  - It is the first time that this paper reports on using improved rabbit blood agar
      culture medium to isolate 145 strains Gardnerella vaginalis from the foxes and
      their abortion fortus organs of main fox farms. Among the strains, 26 strains
      were isolated from the abortion foetus organs, isolation rate was 92.86%; 118
      strains were isolated from the vaginal exeretion of the abortion and empty foxes,
      isolation rate was 34.01%; 1 strain was isolated from inguinal lymph node of the
      pelted positive fox, isolation rate was 2%. None was isolated from blood. By
      causative agent isolation, we revealed the bacterium survival position in vivo,
      and the best isolation route isolation opportunity and isolation methods were
      selected. By artificial infection test, we have proved pathogenicity of the
      bacterium.

PMID- 7725680
TI  - [A new zoonosis--investigation of Gardnerella vaginalis disease of fox. II.
      Identification of pathogenic bacteria].
AB  - 16 strains isolated from aborted foetus and vaginal exeretions of foxes were used
      for examination of cell morphology including fine structure of the cell wall and
      septa, test for homolysis, biochemical reactions and analysis of G+C content of
      the bacterial DNA. The cells are pleomorphic bacilli and coccobacilli, Gram stain
      reaction appear positive to variable, catalse and oxidase-negative, with a
      fermentative type of glucose metabolism, giving acetic and lactic acid as the
      major end products of fermentation. It's differentiated from the human strains of
      G. vaginalis by its less fastidious in growth requirements and being
      facultatively anaerobic to aerobic. We propose the name: a new subspecies-
      Gardnerella vaginalis subsp. fox, the type strain is U80.

PMID- 7725681
TI  - [Studies on elastase from Flavobacterium. I. Strain screening and enzyme
      purification].
AB  - 132 strains bacteria secreting extracellular elastase were isolated from soil
      samples, 5 of them possessed considerably high elastiolytic activity of more than
      100 u/ml. The highest-yield strain No. 17-87 was characterized as Flavobacterium
      odoratum, studies on the condition of elastase production revealed that its
      optimum carbohydrate and nitrogen source were glucose and casein respectively,
      and that it could utilize fowl ferther meal and wheat bran to give 80% relative
      yield. The culture exhibited maximum elastase activity at 26 degrees C for 21
      hours, the productivity could be increased when the aeration was improved. The
      PAGE-homogenous elastase preparation was obtained from the culture broth by
      (NH4)2SO4 fractionation, DEAE-cellulose column chromatography and gel filtration
      on Sephadex G-75. The molecular weight was determined to be 21380 by SDS-PAGE,
      the elastiolytic activity was optimal at pH7.4 and 50 degrees C. The enzyme was
      stable over the range of pH4.5-9.5 and below 40 degrees C, but the activity was
      inhibited completely by Fe3+, Zn2+, Cu2+, Cr3+, Co2+, Ni2+, Hg2+, Ag+.

PMID- 7725682
TI  - [The investigation on actinomycete population and resources in some areas in
      Yunnan. IX. The actinomycetes in the west and the northeast of Yunnan].
AB  - Two hundred of soil samples of primeval forest, secondary forest, wasteland,
      nonirrigated farmland, vegetable farmland and paddy farmland were collected from
      both the west and the northeast of Yunnan in February, 1989. The actinomycetes in
      the samples were isolated and identified by various methods. This paper discussed
      the actinomycete population and its difference in the both areas of Yunnan.

PMID- 7725683
TI  - Prospective evaluation of the safety and efficacy of laparoscopic jejunostomy.
AB  - We prospectively assessed the safety and efficacy of laparoscopic jejunostomy
      done by 11 surgeons in 8 medical centers using the T-fastener technique. In all,
      23 men and 13 women aged 19 to 84 (mean, 59) years required enteral feeding, but
      could not undergo gastrostomy and had no contraindication to laparoscopy. Of
      these patients, 12 had head and neck cancer and 11 had neurologic swallowing
      dysfunction. The procedure took 25 to 180 minutes (mean, 75). Three (8%) early
      cases were converted to open jejunostomy because of accidental enterotomies
      caused by inappropriate techniques that were avoided in later cases. Minor
      technical problems, such as passing a needle through the back wall of the
      jejunum, occurred in 7 patients, but they were easily corrected and produced no
      complications. Feedings were routinely begun within 24 hours of the surgical
      procedure. All jejunostomy catheters functioned well. This is a safe and
      effective technique when done by experienced laparoscopic surgeons, and serious
      complications are rare.

PMID- 7725684
TI  - California physicians' willingness to care for the poor.
AB  - Although generalist physicians appear to be more likely than specialists to
      provide care for poor adult patients, they may still perceive financial and
      nonfinancial barriers to caring for these patients. We studied generalist
      physicians' attitudes toward caring for poor patients using focus groups and used
      the results to design a survey that tested the generalizability of the focus
      group findings. The focus groups included a total of 24 physicians in 4
      California communities; the survey was administered to a random sample of 177
      California general internists, family physicians, and general practitioners. The
      response rate was 70%. Of respondents, 77% accepted new patients with private
      insurance; 31% accepted new Medicaid patients, and 43% accepted new uninsured
      patients. Nonwhite physicians were more likely to care for uninsured and Medicaid
      patients than were white physicians. In addition to reimbursement, nonfinancial
      factors played an important role in physicians' decisions not to care for
      Medicaid or uninsured patients. The perception of an increased risk of being sued
      was cited by 57% of physicians as important in the decision not to care for
      Medicaid patients and by 49% for uninsured patients. Patient characteristics such
      as psychosocial problems, being ungrateful for care, and noncompliance were also
      important. Poor reimbursement was cited by 88% of physicians as an important
      reason not to care for Medicaid patients and by 77% for uninsured patients.
      Policy changes such as universal health insurance coverage and increasing the
      supply of generalist physicians may not adequately improve access to care unless
      accompanied by changes that address generalist physicians' financial and
      nonfinancial concerns about providing care for poor patients.

PMID- 7725687
TI  - Female athlete triad.
AB  - The Council on Scientific Affairs of the California Medical Association presents
      the following epitomes of progress in physical medicine and rehabilitation. Each
      item, in the judgment of a panel of knowledgeable physicians, has recently become
      reasonably firmly established, both as to scientific fact and clinical
      importance. The items are presented in simple epitome, and an authoritative
      reference, both to the item itself and to the subject as a whole, is generally
      given for those who may be unfamiliar with a particular item. The purpose is to
      assist busy practitioners, students, researchers, and scholars to stay abreast of
      progress in medicine, whether in their own field of special interest or
      another.The epitomes included here were selected by the Advisory Panel to the
      Section on Physical Medicine and Rehabilitation of the California Medical
      Association, and the summaries were prepared under the direction of Murray E.
      Brandstater, MD, and the panel.

PMID- 7725686
TI  - Obstructive sleep apnea. Trends in therapy.
AB  - The National Commission on Sleep Disorders Research, in its report to Congress,
      concluded that the primary care community generally does not understand sleep
      disorders. Obstructive sleep apnea carries a risk of substantial morbidity and
      mortality. Excessive daytime sleepiness results from fragmented sleep and
      microarousals associated with apneic events. It causes poor work performance and
      increases the incidence of automobile accidents due to driving while drowsy. The
      commission estimates that the loss of productivity in the United States from
      excessive daytime sleepiness is more than $20 billion per year. Obstructive sleep
      apnea is strongly associated with hypertension, myocardial infarction, and
      stroke. Risk factors for obstructive sleep apnea include male sex, obesity, older
      age, craniofacial anomalies, and familial risk. Treatment is based on documenting
      the disorder by polysomnography. Medical management of the syndrome includes
      weight loss and nasal continuous positive airway pressure. A network of follow-up
      and support is necessary to maintain compliance. Surgical treatment is reserved
      for those for whom nasal airway pressure treatment fails. A surgical protocol is
      presented that demonstrates efficacy equal to nasal airway pressure treatment.
      Primary care physicians should assume the responsibility of identifying patients
      at risk for obstructive sleep apnea and refer them appropriately.

PMID- 7725685
TI  - Fulminant Mycoplasma pneumoniae pneumonia.
AB  - The frequency of fulminant pneumonia due to Mycoplasma pneumoniae is relatively
      rare despite the high prevalence of Mycoplasma species infection in the general
      population. We recently encountered such a case and have reviewed the English
      language literature on cases of M pneumoniae pneumonia that have resulted in
      respiratory failure or death. Due to host factors or on epidemiologic grounds,
      fulminant cases seem to be more common in young healthy adults, in males, and
      possibly in smokers among the 46 patients we found. An enhanced host cellular
      immune response may be responsible for the development of severe cases. A
      spectrum of small airways disease is characteristic, including cellular
      bronchiolitis and bronchiolitis obliterans with and without organizing pneumonia.
      Based largely on anecdotal experience, corticosteroid use may be salutary in
      patients with respiratory failure. For reasons that are not well known, the
      incidence of pulmonary thromboembolism is increased in fatal cases.

PMID- 7725688
TI  - Diagnosing tibial stress injuries in athletes.

PMID- 7725689
TI  - Alcohol use and traumatic brain injury.

PMID- 7725690
TI  - Hemiplegic shoulder pain--early prevention and rehabilitation.

PMID- 7725691
TI  - Acute ankle and foot injury--guidelines for radiography.

PMID- 7725692
TI  - Influence of disability on pregnancy and motherhood.

PMID- 7725693
TI  - Birth brachial plexus injury.

PMID- 7725694
TI  - Urticarial skin lesions and polymyositis due to lymphocytic vasculitis.

PMID- 7725695
TI  - Impotence related to anabolic steroid use in a body builder. Response to
      clomiphene citrate.

PMID- 7725696
TI  - Lead poisoning in a radiator repairer.

PMID- 7725697
TI  - Scenarios for success--enhancing women physicians' professional advancement.

PMID- 7725698
TI  - Treating obstructive sleep apnea syndrome--a complex task.

PMID- 7725699
TI  - Severe Mycoplasma disease--rare or underdiagnosed?

PMID- 7725700
TI  - More on lovastatin.

PMID- 7725701
TI  - A patient's paper chase.

PMID- 7725702
TI  - Pregnant teenagers.

PMID- 7725703
TI  - Hypertension. Preoperative assessment and perioperative management.
AB  - Hypertension is a frequently encountered abnormality in patients being prepared
      for surgical procedures. This condition complicates anesthetic and postoperative
      management, but careful monitoring and treatment allow hypertensive patients to
      tolerate surgery safely. Particular attention should be directed toward
      continuing antihypertensive medicine until the time of the surgical procedure or
      initiating treatment before it, monitoring the blood pressure frequently after
      the operation, and controlling postoperative hypertension with one of many
      parenteral agents available. The possibility of the presence of secondary
      hypertension and cardiovascular complications of hypertension should be
      considered during the preoperative assessment.

PMID- 7725704
TI  - Review of hepatic abscess from Klebsiella pneumoniae. An association with
      diabetes mellitus and septic endophthalmitis.
AB  - I present the only comprehensive review of hepatic abscess from Klebsiella
      pneumoniae. The world literature contains 46 individually reported cases and 3
      large studies of K pneumoniae liver abscess. The source of the abscesses
      frequently was not found. Diabetes mellitus was a frequent underlying condition
      and may predispose patients to the development of liver abscess with this
      organism. The exact mechanism is unclear, and further investigation is necessary.
      In addition, extrahepatic metastases, such as septic endophthalmitis, often
      occurred with serious complications, particularly in patients with diabetes. The
      association between K pneumoniae liver abscess and diabetes is so close that a
      search for underlying diabetes mellitus is warranted in all patients with K
      pneumoniae liver abscess. Fortunately, earlier diagnoses and better treatment
      modalities have improved the outcome for these patients.

PMID- 7725705
TI  - Methotrexate therapy. Nonsurgical management of ectopic pregnancy.
AB  - Ectopic pregnancy has become a surgical epidemic over the past two decades. To
      minimize the morbidity, mortality, and financial burden created by this rapidly
      growing health problem, nonsurgical alternatives have been investigated,
      including treatment with methotrexate. We reviewed current literature to evaluate
      the safety, efficacy, and costs associated with methotrexate treatment of tubal
      pregnancy. To date, 17 studies have reported on 400 patients with tubal
      pregnancies treated with parenteral methotrexate; the overall success rate was
      92% (95% confidence interval, 89% to 95%). Single-dose parenteral methotrexate
      has been shown to be safe, effective, and associated with minimal costs when used
      in carefully selected patients. A prospective, randomized clinical trial
      comparing medical and surgical management of ectopic pregnancy is needed to
      assess the risks, benefits, and costs of these two approaches.

PMID- 7725706
TI  - Making the health care system 'safe' for persons with HIV infection or AIDS.
AB  - If health care reform is implemented in states and nationally, the safety of this
      process needs to be examined for persons with human immunodeficiency virus (HIV)
      infection or the acquired immunodeficiency syndrome (AIDS). Reform should assure
      ongoing prevention and transmission control of HIV and continuous coverage of
      medical costs for persons ill with HIV or AIDS. These persons currently benefit
      from various state and federal categoric programs designed to assure access to
      preventive and personal care services. Washington State has passed health care
      reform legislation that envisions integrating these programs to provide a system
      of population-based and personal health care. This legislation was analyzed using
      existing epidemiologic and entitlement information about persons with HIV
      infection or AIDS in the state to assess its effect. The relationship between
      public health and personal care services will be a central concern for those with
      HIV infection or AIDS, and complete coverage of this group may be achieved
      relatively late in the process of implementing health care reform. Health
      personnel planning under health care reform will affect the delivery of HIV- and
      AIDS-related services. Including treatment of AIDS in the basic benefit package
      merits particular attention. These issues parallel those being faced by the
      nation as a whole as it seeks to ensure epidemic disease control and
      compassionate care for long-term disabling illness if health care reform is
      implemented.

PMID- 7725707
TI  - Total hip arthroplasty.
AB  - Total hip arthroplasty, or surgical replacement of the hip joint with an
      artificial prosthesis, is a reconstructive procedure that has improved the
      management of those diseases of the hip joint that have responded poorly to
      conventional medical therapy. In this review we briefly summarize the evolution
      of total hip arthroplasty, the design and development of prosthetic hip
      components, and the current clinical indications for this procedure. The possible
      complications of total hip arthroplasty, its clinical performance over time, and
      future directions in hip replacement surgery are also discussed.

PMID- 7725709
TI  - Stereotactic neurosurgery for Parkinson's disease.
AB  - The Council on Scientific Affairs of the California Medical Association presents
      the following epitomes of progress in neurosurgery. Each item, in the judgment of
      a panel of knowledgeable physicians, has recently become reasonably firmly
      established, both as to scientific fact and clinical importance. The items are
      presented in simple epitome, and an authoritative reference, both to the item
      itself and to the subject as a whole, is generally given for those who may be
      unfamiliar with a particular item. The purpose is to assist busy practitioners,
      students, researchers, and scholars to stay abreast of progress in medicine,
      whether in their own field of special interest or another. The epitomes included
      here were selected by the Advisory Panel to the Section on Neurosurgery of the
      California Medical Association, and the summaries were prepared under the
      direction of John H. Neal, MD, and the panel.

PMID- 7725708
TI  - A 15-year-old girl with acute renal failure. Clinicopathologic conference.

PMID- 7725710
TI  - Cardiac bypass and hypothermia in the treatment of complex aneurysms.

PMID- 7725711
TI  - Functional mapping for surgically removing brain tumors.

PMID- 7725713
TI  - Tethered cord syndrome.

PMID- 7725712
TI  - Percutaneous discectomy--update.

PMID- 7725714
TI  - Managing chronic intractable pain.

PMID- 7725716
TI  - Stabilizing the cervical spine.

PMID- 7725718
TI  - Role of spinal instrumentation in fusion for degenerative disease of the
      lumbosacral spine.

PMID- 7725715
TI  - Dorsal rhizotomy for spasticity.

PMID- 7725717
TI  - Neuroendoscopy.

PMID- 7725719
TI  - Carotid endarterectomy.

PMID- 7725720
TI  - California's public health policy on preventing neural tube defects by folate
      supplementation.

PMID- 7725721
TI  - Sustained atrial fibrillation after dobutamine stress echocardiography in an
      older patient with left atrial enlargement.

PMID- 7725722
TI  - Rhabdomyolysis from tourniquet trauma in a patient with hypothyroidism.

PMID- 7725723
TI  - Total hip arthroplasty--a cure?

PMID- 7725724
TI  - Intracavitary mass in a patient with tuberculous pneumonia.

PMID- 7725725
TI  - Ocular infections.

PMID- 7725726
TI  - Intravenous immune globulin.

PMID- 7725727
TI  - Rural physicians--in crisis?

PMID- 7725730
TI  - "The" pheochromocytoma: a benign, intra-adrenal, hypertensive, sporadic
      unilateral tumor. Does it exist?
AB  - This study aims to examine the frequency of the pheochromocytoma (pheo), defined
      as a "benign, intra-adrenal, hypertensive, sporadic, unilateral tumor." Three
      large series amounting to 310 subphrenic chromaffin tumors operated over periods
      of 17, 23, and 41 years, respectively, have been reviewed. Among those combined
      310 pheos, 48 (15.5%) were malignant (i.e., metastatic) and 262 (84.5%) were
      benign; 42 (13.5%) were ectopic (35% of malignant tumors versus 9.5% of benign
      tumors); 230 (74.2%) were hypertensive (74% of benign tumors versus 73% of
      malignant tumors); 29 (9.4%) were bilateral, including 23 patients with a family
      history; 41 (13.2%) of patients had MEN II type A or B syndrome; and 20 (6.5%)
      occurred in a phacomatosis setting. Some of the patients had a non-MEN family
      history of pheo (n = 5), seemingly sporadic hyperparathyroidism (n = 4), or other
      associated neuroendocrine tumor (n = 9). Sometimes several of these features were
      combined. Finally 125 (40.3%) cases fitted the classic description of the tumor,
      47.0% at the time of initial presentation and 40.3% at the end of follow-up. Late
      occurrence of metastases or metachronous diagnosis of familial disease make
      lifelong follow-up mandatory. Genetic studies may be indicated in
      pheochromocytoma patients.

PMID- 7725728
TI  - Point mutations of ras genes in human adrenal cortical tumors: absence in
      adrenocortical hyperplasia.
AB  - Point mutations of ras genes (K-, H-, and N-ras) at codons 12, 13, and 61 and of
      the Gi2 alpha gene at codons 179 and 205, were studied in 56 primary adrenal
      cortical tumors and 6 adrenal cortical hyperplasias. Of 56 tumors, 24 were
      carcinomas and 32 were benign. The 24 carcinomas and 20 of the benign tumors were
      from American patients; the 12 remaining adenomas were from Japanese patients. Of
      the benign tumors 12 were cortisol-producing adenomas, 15 were aldosterone
      producing adenomas, 3 were nonfunctioning adenomas, and 2 were adenomas that
      produced a virilizing syndrome. Tumor DNA obtained from archival formalin-fixed,
      paraffin-embedded tissue or fresh frozen tissue was amplified by polymerase chain
      reaction; and point mutations were detected by sequence-specific oligonucleotide
      hybridization. Activating ras mutations were found in 7 of 56 (12.5%) of all
      tumors: 3 of 24 (12.5%) carcinomas and 4 of 32 (12.5%) adenomas. Of adenomas from
      an American population, 4 of 20 (20%) exhibited positive ras mutations, whereas
      none was present in the Japanese tumors. All mutations detected were adenine to
      guanine transitions at the second position of N-ras codon 61, resulting in a
      conversion from glutamine to arginine. No mutations were found in K-ras or H-ras
      genes. Furthermore, no mutations of the Gi2 alpha gene were identified. These
      findings demonstrate that N-ras mutations at codon 61 may contribute to the
      genesis of both benign and malignant human adrenal cortical tumors. Finally, no
      mutations of the ras or Gi2 alpha genes were identified in hyperplastic
      adrenocortical tissues.

PMID- 7725731
TI  - Diverse clinical and pathologic features of gastric carcinoid and the relevance
      of hypergastrinemia.
AB  - The etiology, prognosis, and optimal management of primary gastric carcinoids
      remain controversial. Records of 36 consecutive patients with gastric carcinoid
      (15 men) were reviewed retrospectively between 1975 and 1990. Follow-up was
      complete in 97% of cases. Mean age at diagnosis was 58.4 years (range 24-82
      years). The clinical presentations included anemia (72%), pain (69%), and
      carcinoid syndrome (11%). Associated autoimmune and endocrine abnormalities were
      common and included atrophic gastritis (67%), pernicious anemia (58%),
      hypothyroidism (39%), diabetes (19%), Addison's disease (6%), and
      hyperparathyroidism (6%). Lesions were nonantral in 78%, involving only the
      corpus in 42%, the fundus in 28%, and only the antrum in 8%; 42% were multiple.
      Urinary 5-hydroxyindoleacetic acid (5-HIAA) and serum gastrin levels were
      elevated in 17% and 50% of those tested, respectively. Histologic examination
      revealed that 28% of lesions were > or = 2 cm, and 33% had liver metastases on
      presentation or developed them during follow-up. Eight patients (22%) died of
      tumor with a median survival of 39 months. The presence of metastases, atypical
      histology, serosal involvement, and size > 2 cm were adverse prognostic factors.
      In patients without hypergastrinemia (n = 6), 66% developed metastases, 60% had
      elevated 5-HIAA, and 50% died of carcinoid tumor. In sharp contrast, those
      patients with hypergastrinemia and "typical" gastric carcinoids (n = 15),
      metastases and death did not occur (p < 0.003 and p < 0.005, respectively,
      compared with eugastrinemic patients).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725729
TI  - Role of bilateral adrenalectomy in Cushing's disease.
AB  - Of 206 patients with Cushing's syndrome observed from 1975 through 1991, 144
      (69.9%) had pituitary-dependent Cushing's disease. Of the 110 patients who
      underwent pituitary surgery, 31 (28%) developed an early recurrence and 23
      patients (20%) had a late relapse 1 to 5 years after primary pituitary
      exploration. We performed a one- or two-step total bilateral adrenalectomy in 43
      patients-9 men and 34 (79.4%) women, with an average age of 47.5 years (range 13
      58 years). Thirty-three of these patients had already been treated by previous
      transsphenoidal surgery or alternatively by external pituitary irradiation over a
      period of 1 to 10 years prior to adrenal surgery. Thirty-one patients underwent
      adrenalectomy by a double lumbar access or left lumbar and right subcostal
      incisions. In our series of 55 operations, perioperative complications included
      two splenectomies and two hemorrhages (7.3%). The early mortality rate was 3.6%
      (two patients). Minor complications consisted of wound infection (13.5%),
      bronchopneumonia or pneumothorax (four cases) with a 7- to 12-day longer hospital
      stay. Nelson syndrome occurred in 6 of 41 patients (14.6%). We therefore believe
      that bilateral adrenalectomy does play a major role in the treatment of patients
      with pituitary-dependent Cushing's disease unsuccessfully managed by
      transphenoidal surgery. It represents the definitive therapy for those patients
      in whom hypophysectomy was not able to provide satisfactory control of the
      disease.

PMID- 7725733
TI  - Surgical management of insulinoma associated with multiple endocrine neoplasia
      type I.
AB  - Insulinoma in patients with multiple endocrine neoplasia (MEN) is a rare
      condition that because of its usual multicentricity presents difficulties not
      encountered in sporadic patients. In contrast to gastrinoma, which is the most
      common pancreatic neoplasm associated with MEN I, malignancy and duodenal tumors
      are much less common for patients with insulinomas, and excellent palliative
      medication is not available. Accordingly, there is a much greater reliance on
      surgical therapy for this group of patients. Between 1970 and 1991 a total of 19
      patients had surgical treatment of MEN I-related insulinoma. Each patient had
      hyperinsulinemic hypoglycemia. One patient, with extensive metastases, had
      unresectable disease. Of the remaining 18, there were 16 (89%) multiple
      pancreatic tumors. Tumors were located in the neck, body, or tail in 17 cases, 10
      of whom also had tumors in the head. Pancreatic resections performed were 1
      total, 12 subtotal (7 also had enucleation of tumors from the pancreatic head),
      and 5 limited distal resections and/or enucleation (conservative resection).
      There was no operative mortality. One patient developed pancreatitis, fistula,
      and diabetes following subtotal resection and enucleation. Postoperative cure was
      achieved in 17 of 18 cases. Recurrent disease occurred in 2 of 5 conservative
      resections compared to 0 of 12 subtotal resections, with median follow-up times
      of 10.4 and 10.3 years, respectively. During the follow-up period, four patients
      died, possibly all due to MEN I-related conditions. Hyperinsulinism in MEN I is
      associated with the occurrence of multiple, usually benign, pancreatic islet cell
      tumors, and surgery is an effective treatment modality.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7725734
TI  - Fate of untreated benign thyroid nodules: results of long-term follow-up.
AB  - The fate of benign thyroid nodules has been unknown because there has been no
      study in this regard. We re-examined 134 patients with thyroid nodules who had
      had benign aspiration biopsy cytology 9 to 11 years ago. The thyroid gland was
      palpated by the same two thyroidologists throughout the study. Ultrasonography,
      fine-needle aspiration biopsy (FNAB), and ultrasound-guided FNAB were employed to
      examine the nature of nodules of 9 to 11 years' duration. Patients (n = 61) who
      had nodules difficult to palpate (small nodules), multiple nodules, or cystic
      nodules with papillomatous proliferation underwent ultrasound-guided FNAB;
      patients (n = 55) having a distinctly palpable single nodule underwent usual
      FNAB. None of the patients received any medical or surgical treatment. There were
      86 single nodules, 14 multiple nodules, and 34 cystic nodules on the first
      examination. These benign nodules were reexamined for changes in size and
      cytology 9 to 11 years later. The most striking finding was a decrease in size or
      disappearance of the nodule in 42% to 79% of benign nodules. About 92% of nodules
      remained benign without changing cytologic classification. Only one case (0.9%)
      previously regarded as benign turned out to be malignant; this nodule grew in
      size compared with the previous examination. Among single and multiple nodules,
      21% to 23% of the nodules increased in size; however, most patients with enlarged
      nodules (86%) showed the same class 2 cytology as before. Our present study
      indicates that biopsy-proved benign thyroid nodules remain benign over a
      prolonged period. Thus no medical or surgical treatment is required so long as
      the nodules do not grow.

PMID- 7725732
TI  - MHC class I and II antigen expression and interferon alpha treatment of human
      midgut carcinoid tumors.
AB  - Cryosections of 28 primary and metastatic midgut carcinoid tumors from 12
      patients with carcinoid syndrome were investigated immunohistochemically with
      antibodies that recognize human MHC class I (HLA-ABC) and class II (HLA-DR)
      antigens. The tumor parenchyma of all six patients treated with interferon alpha
      (IFN-alpha) during a mean 8.6 months (3 x 10(6) to 5 x 10(6) U three times
      weekly) exhibited unequivocal HLA-ABC immunoreactivity, with only minor
      discrepancies between primary lesions and metastases in mesenteric lymph nodes
      and liver. Class I staining was absent on the tumor cells of all 14 specimens
      from the patients without IFN therapy but was induced by culturing freshly
      dispersed tumor cells in vitro for 48 hours in the presence of recombinant IFN
      alpha. The stroma of all neoplasms displayed class I and II immunostaining, as
      did usually a few CD4-expressing cells. The carcinoid specimens lacked
      parenchymal HLA-DR immunoreactivity, which is interesting considering suggestions
      on improved prognosis for bowel carcinomas lacking the class II expression. The
      study supports the idea that induction of MHC class I antigens could contribute
      to the beneficial clinical effect of IFN-alpha treatment in patients with midgut
      carcinoid tumors.

PMID- 7725735
TI  - Expression of basic fibroblast growth factor in thyroid disorders.
AB  - Morphologic and biologic studies were undertaken to clarify the biologic
      significance of basic fibroblast growth factor (bFGF) in human thyroid neoplasms.
      A total of 71 malignant tumors (50 papillary carcinomas, 14 follicular
      carcinomas, 7 anaplastic carcinomas), 11 follicular adenomas, 6 adenomatous
      goiters, and 6 Graves' disease tissues were examined employing
      immunohistochemical methods (avidin-biotin-peroxidase complex technique). An
      affinity-purified polyclonal rabbit antiserum to human bFGF was used as a primary
      antibody. The eluate of malignant thyroid tumor tissues from the heparin
      Sepharose column was examined by Western blot analysis to elucidate the molecular
      weight form. With immunohistochemical staining, bFGF was frequently detected in
      the cytoplasm of malignant thyroid tumors compared to tissues of the benign
      diseases and normal controls. With anaplastic carcinoma, immunoreactivity of the
      tumor cells was particularly strong. In the correlative analyses between UICC TNM
      classification and bFGF staining in papillary carcinoma, there were significant
      differences when relating positive staining to the grade of nodal metastases. By
      Western blot analysis, the bFGF immunoreactivity was specifically detected in the
      two forms, with molecular weights of 18 and 33 kDa. The high-molecular-weight
      form was detected in only anaplastic carcinoma. The present investigations
      demonstrated a close correlation between the expression of bFGF and the degree of
      malignancy. bFGF might play an important role in promoting lymph node metastases.
      Moreover, the high-molecular-weight form of bFGF might have an intense influence
      on tumor growth.

PMID- 7725736
TI  - Preoperative diagnostic tests for operable thyroid disease.
AB  - Although the availability and acceptance of fine-needle aspiration biopsy (FNAB)
      of thyroid nodules has increased, many physicians still use thyroid scintigraphy
      for distinguishing benign from malignant lesions. We evaluated these diagnostic
      tests in 350 patients who had thyroid surgery in our institution between 1977 and
      1990. Histologic confirmation of FNAB was obtained in 265 patients. In the group
      of patients having surgery, 247 thyroid scintigraphies were performed. Our
      patients were divided into two groups (1977-1986 and 1986-1990). The first group
      comprised 173 patients with 173 FNABs and 126 scintigrams. The second group
      consisted of 177 patients having 92 FNABs and 121 scintigrams. Results of
      scintigrams were analyzed in the second group only. In 5 out of 120 cases where
      the FNAB result was "benign or probably benign" the lesion appeared to be
      malignant postoperatively. If the FNAB result was "malignant or probably
      malignant" (n = 83) the pathology report confirmed a malignancy in 68 cases
      (81.9%). In 56 instances of all 265 FNABs the cytology report was not conclusive
      ("uncertain"); in 21.4% of these cases a malignancy was found postoperatively. An
      FNAB-result "(probably) malignant" had a positive predictive value of 0.819 while
      the negative predictive value of a result "(probably) benign" is 0.950. An
      "uncertain" result does not take away our concern so this result should have the
      same consequences as those of a result "(probably) malignant". In that case, FNAB
      sensitivity is 93.0% and specificity 66.1%. Eighty-five of the last 116
      scintigraphies showed a solitary node. Eleven of these nodes were hot while 74
      were cold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725737
TI  - Proton magnetic resonance and human thyroid neoplasia. II: Potential avoidance of
      surgery for benign follicular neoplasms.
AB  - Thyroid cancer is rare, but many thyroidectomies continue to be performed simply
      to exclude a diagnosis of malignancy. The purpose of this study was to determine
      the potential financial savings associated with the use of proton magnetic
      resonance analysis of follicular neoplasms. Proton magnetic resonance
      spectroscopy was performed on tissue obtained at the time of surgery from 98
      consecutive solitary or dominant thyroid nodules. Fine-needle biopsies were also
      performed on operative specimens, and the tissues assessed by proton magnetic
      resonance; these spectra were then compared with those obtained from tissue
      specimens. An estimate of potential savings was obtained by comparing the
      magnetic resonance data with the indications for surgery and pathology on all
      patients having thyroidectomy over a 10-year period. Proton magnetic resonance
      spectroscopy was able to distinguish between normal thyroid tissue and invasive
      thyroid cancer with 100% specificity. Benign follicular adenomas fall into two
      groups: 44% having a spectral pattern comparable with normal thyroid, and the
      remaining 56% demonstrating an altered spectral pattern more comparable to the
      malignant magnetic resonance profile. Proton magnetic resonance spectroscopy on
      fine-needle biopsy specimens produced spectra similar to those from tissues from
      the same patient. From a fine-needle biopsy specimen, proton magnetic resonance
      spectroscopy can identify a group of benign follicular adenomas with spectral
      profiles akin to those of normal thyroid cells, thus avoiding the need for
      unnecessary surgical excision. The potential savings in one surgical unit alone
      were over $1 million in 10 years.

PMID- 7725738
TI  - Thyroid carcinoma after radioactive iodine therapy for Graves' disease.
AB  - Although the causal relation between radioactive iodine therapy (RIT) for Graves'
      disease and the subsequent occurrence of thyroid carcinoma is not definite,
      surgeons may be faced with the treatment of such patients. We studied the
      clinicopathologic features of patients with thyroid carcinoma following RIT for
      Graves' disease. From January 1983 to December 1991, 11 patients with thyroid
      carcinoma occurring 1 year or more after RIT for Graves' disease underwent
      surgery at Ito Hospital. These 11 patients accounted for 0.51% of 2146 surgical
      cases of thyroid carcinoma and 0.17% of 6419 RIT cases of Graves' disease during
      the period. They were all women, and their mean ages at RIT and surgery were 44.3
      and 51.4 years, respectively. The administered dose of RI was 222.1 MBq and the
      absorbed dose 45.3 Gy on average. Total thyroidectomy was performed in two
      patients, subtotal thyroidectomy in three, and lobectomy in six. Bilateral
      modified neck dissection (MND) was added in two patients, and ipsilateral MND in
      seven. Histology revealed 10 papillary and 1 follicular carcinoma. The mean
      diameter of the tumor was 18.5 mm. Intraglandular dissemination of the tumor was
      noted in only one case and solid growth pattern in two. Nodal metastasis was
      disclosed in six cases, but in five of them only one node was involved. The
      present study indicated that thyroid carcinoma occurring after RIT for Graves'
      disease is not an aggressive variety, and thyroid lobectomy with ipsilateral MND
      would be sufficient as surgical treatment for such patients.

PMID- 7725739
TI  - Radioiodine-associated thyroid cancers.
AB  - Numerous investigations document that exposure to low dose external therapeutic
      radiation leads to the development of benign and malignant thyroid neoplasms.
      There is considerable controversy, however, concerning whether radioactive iodine
      (131I) causes thyroid cancer. The aim of this investigation was to examine our
      experience and that in the literature related to this problem. From 1982 to March
      1993 seven of 373 patients (1.9%) with thyroid cancer who were treated by one
      surgeon had a history of treatment with radioactive iodine for Graves' disease
      and toxic nodular goiter. Sixty-five patients have previously been reported in
      the literature from 1957 to present. Our patients (five women, two men) ranged in
      age from 26 to 80 years (mean 57 years). The interval between the exposure to the
      internal radiation and development of cancer ranged from 3 to 29 years (mean 11.4
      years), and the mean age at the time of 131I treatment was 45 years (18-76
      years). The therapeutic dose of 131I was 5 to 100 mCi (mean 25.3 mCi) in our
      patients. Two of our patients received 131I twice. The age of patients reported
      in the literature at the time of 131I treatment ranged from 7 to 74 years (mean
      48 years). The mean therapeutic dose of 131I was 20.6 mCi (1.25-180.0 mCi) and
      the latent period was documented for a mean 8.7 years (0.25-28.0 years) in these
      patients. Three of 29 patients in the literature received 131I twice. Fine-needle
      aspiration cytology of thyroid nodules was positive for cancer in six of our
      patients (86%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725740
TI  - Thyroperoxidase immunodetection for the diagnosis of malignancy on fine-needle
      aspiration of thyroid nodules.
AB  - We have previously demonstrated that in 95.6% of malignant thyroid tumors the
      enzyme thyroid peroxidase (TPO) presents antigenic changes detectable by a
      monoclonal antibody termed MoAb47. The aim of this study was to investigate the
      interest of TPO immunodetection for the diagnosis of malignancy on fine-needle
      aspiration biopsy (FNAB) of thyroid nodules. The study was performed on 300
      patients. Slides of FNAB aspirate were air-dried and stained by anti-TPO-MoAb47.
      According to the percentage of TPO-positive epithelial cells, patients were
      divided into two groups: benign (> 80%) and malignant (< 80%). In 279 cases
      additional slides were available for Giemsa stain and standard cytology. All the
      patients were operated on, and the final diagnosis was recorded as benign in 248
      cases (183 macrofollicular nodules, 23 microfollicular adenomas, 18 atypical
      adenomas, 11 oncocytomas, 11 thyroiditis, 2 Graves' disease) and malignant in 52
      cases (44 papillary carcinomas and 8 follicular carcinomas). Samples from 215 of
      248 benign nodules yielded 80% to 100% TPO-positive cells, whereas samples from
      all malignant tumors yielded less than 80% positive cells. The sensitivity of TPO
      staining for diagnosis of malignancy was thus 100%, its specificity 86.7%, and
      its overall accuracy 89%. With conventional cytology, sensitivity, specificity,
      and accuracy were 91.6%, 79.2%, and 81.0%, respectively. We conclude from this
      study that TPO staining with MoAb47 should become an essential adjunct in the
      preoperative cytologic diagnosis of thyroid nodules.

PMID- 7725742
TI  - Rarity of squamous cell carcinoma of the thyroid: autopsy review.
AB  - Squamous cell carcinoma (SCC) of the thyroid is thought to be rare. However, SCC
      not infrequently occurs in conjunction with other histologic types of tumor. We
      reviewed 67 thyroid cancer autopsy cases obtained from two institutions from 1969
      to 1981 and from 1975 to 1992, respectively. SCC was found in 19 cases (28.4%): 2
      SCCs as the only malignancy and of uniform histologic type, 9 cases of tumors
      mixed with papillary carcinoma, and 8 cases of SCC mixed with papillary and
      anaplastic carcinomas. In only four of these cases was the SCC component found in
      the surgical specimens. These results indicate that the presence of SCC component
      is more likely to be found at the later stage of the disease.

PMID- 7725741
TI  - Significance of P53 in human thyroid tumors.
AB  - Mutational changes in the p53 tumor suppressor gene are the most frequent genetic
      alterations in human malignant tumors. Studies have shown a correlation of p53
      expression in breast cancer with tumor prognosis. In contrast to mutational
      activation of ras and GSP in thyroid tumors, little is known about the role of
      p53 in thyroid tumor development. Therefore thyroid tumors and thyroid tumor cell
      lines were studied for the presence of p53 mutations. Snap-frozen tissues from 57
      differentiated thyroid carcinomas (DTCs) and 5 goiters were studied by
      immunohistochemical methods. A panel of six antibodies (pAb 240, 421, 1620, 1801,
      DO7, and CM1) was employed by using the ABC technique. Five cell lines from DTCs
      (FTC133, 236, 238, PTC337, MTC164) were examined by the same technique.
      Additionally, genomic DNA from the cells was amplified by the polymerase chain
      reaction (PCR) and the PCR product studied for p53 mutations (R273H) by mutation
      specific oligonucleotide hybridization (MOH) and temperature gradient gel
      electrophoresis (TGGE) for the p53 exon 8. None of the benign thyroid tumors and
      7 of 57 (12%) DTCs strongly express p53 with a heterogeneous distribution in the
      tumor tissue. All seven patients have metastatic disease or dedifferentiated
      tumors G3 (three of seven). CM1 was positive in two cell lines (FTC-133, PTC
      337), questionable in FTC-238, and negative in FTC-236 and MTC-164. All three
      follicular cell lines, however, and the original tumor tissue showed the same p53
      mutation (R273H) in MOH analysis and TGGE. P53 mutations are rare in thyroid
      tumors, but the presence of p53 mutations indicates a poor prognosis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7725743
TI  - Multivariate analysis of risk factors influencing survival in 110 ethnic Chinese
      with papillary thyroid cancer.
AB  - Data from 110 Chinese patients presenting with papillary thyroid cancer to a
      single institution up to December 1985 have been analyzed to evaluate the
      possible risk factors affecting survival. There were 83 women and 27 men with an
      age range of 15 to 78 years (mean 45 years, median 42 years). The longest follow
      up period is 39 years and the median 10 years. Cervical lymph node recurrence
      more than 6 months after surgery developed in 12 patients, of whom 1 died with a
      concomitant distant metastasis. "Thyroid bed" tumor recurrence, after apparently
      complete surgery, presented in 10 patients and resulted in 5 deaths. Distant
      metastases were identified in 17 patients with 7 deaths. Another 4 patients died
      from advanced local disease incompletely resectable on presentation. The
      following seven risk factors for survival were selected for multivariate
      analysis: age, sex, tumor size, histologic evidence of extrathyroidal spread,
      lymph node recurrence, neck recurrence, and distant metastases. Age, size, neck
      recurrence, and distant metastases were all significant on univariate analysis.
      Using Cox proportional hazards regression in the multivariate analysis of these
      seven factors, only age (p < 0.0001) was shown to be significant. Age over 40
      years on first diagnosis was a highly significant indicator of high risk (p =
      0.0003, log-rank).

PMID- 7725744
TI  - Classification of papillary cancer of the thyroid based on prognosis.
AB  - Between 1965 and 1988 there were 2953 patients with papillary carcinoma treated
      at Noguchi Thyroid Clinic. Among them 761 patients were excluded because the
      primary tumor was < 10 mm in maximum diameter, the patient's age was > 80, or the
      patient underwent noncurative surgery. The remaining 2192 patients, 192 men and
      2000 women, were analyzed. The mean follow-up period was 12.5 years. Total
      thyroidectomy, subtotal thyroidectomy, lobectomy with or without isthmectomy, and
      less than lobectomy were performed in 2.3%, 40.3%, 44.2%, and 13.2%,
      respectively. Modified radical neck dissection, partial node excision, and no
      node excision were performed in 77.8%, 6.4%, and 15.8%, respectively. Men and
      women were separately analyzed because their risk factors and prognosis were
      significantly different. Multivariate analysis was carried out according to Cox's
      regression hazard model. Independently significant factors affecting prognosis in
      men were aged and gross nodal metastasis; and age, gross nodal metastasis, tumor
      size, and number of adhered tissues or organs were the factors in women. Based on
      those risk factors patients were classified into three groups. For men, 65.6%
      were classified in the excellent group and their 10-year survival was 98.4%;
      17.2% were classified as intermediate and 17.2% as poor with survival rates of
      90.1% and 74.4%, respectively. For female patients 69.6% were classified in the
      excellent group, 18.6% in the intermediate group, and 11.9% in the poor group
      with 10-year survivals of 99.3%, 96.4%, and 88.8%, respectively.

PMID- 7725745
TI  - Prognostic significance and surgical management of locoregional lymph node
      metastases in papillary thyroid cancer.
AB  - We studied the records of 342 patients with papillary thyroid carcinoma out of a
      total of 728 thyroid cancer patients treated at the Medical School of Hannover
      (MHH) from 1972 through 1992. The comprehensive data-abstracting forms were
      designed, and the acquired information was coded, stored, maintained, and
      evaluated by the Clinical Cancer Registry of the MHH. A total of 160 patients
      (46.8%) initially had lymph node metastases (N1 status). The N status
      significantly influenced recurrence (p < 0.00001) and survival (p < 0.00001).
      Excluding other risk factors developed by univariate and multivariate analysis,
      such as high age (age > 45 years, p < 0.001), tumor invasion (T4 tumor, p <
      0.005), and distant metastases (M1, p < 0.001), lymph node metastases remained an
      independent, highly significant prognostic marker for more aggressive papillary
      thyroid cancer. N1 status did not influence survival of patients with T4 tumor
      but did influence those with T1-T3 status (p < 0.001). The influence of N1 status
      remained significant in patients older (p < 0.001) and younger (p < 0.05) than 45
      years of age. Systematic compartment-oriented dissection of lymph node metastases
      improved survival (p < 0.005, T1-T3) and recurrence (p < 0.00001, T1-T3)
      especially in patients with T1-T3 tumors. In conclusion, lymph node metastases
      with a significant incidence at a young age and male sex had a substantial effect
      on survival and recurrence especially in those with tumor status T1-T3.
      Systematic compartment-oriented dissection of the lymph node metastases results
      in better survival and a lower recurrence rate.

PMID- 7725746
TI  - Diminished expression of the alpha 5 beta 1 integrin (fibronectin receptor) by
      invasive clones of a human follicular thyroid cancer cell line.
AB  - Altered adhesion plaques have been observed in transformed cell lines and are
      associated with enhanced metastatic potential. The prototypical adhesion plaque
      is formed by alpha 5 beta 1 fibronectin receptors (FnRs) interacting with the
      cellular actin network. We have found differences in the actin networks of
      noninvasive (FTC-133) and invasive (FTC-236, FTC-238) clones of a human
      follicular thyroid cancer cell line. Furthermore, thyroid-stimulating hormone
      (TSH) induces stress fibers in FTC-133. In order to investigate differences in
      adhesion plaques, expression of fibronectin (FN) and its receptor by these cells
      was analyzed. For these studies FTC-133, FTC-236, and FTC-238 were cultured in
      serum-depleted DME-H21 medium for 24 hours before the addition of TSH 30 mU/ml.
      No quantitative differences were noted in FN expression on Western blot in either
      the conditioned medium or cellular extracts. Western blots and
      immunohistochemical studies indicated that TSH induced secretion of FN only in
      FTC-133. Flow cytometry with an alpha 5 antibody demonstrated a 52% and 45%
      reduction (p < 0.01) in expression of FnR by FTC-236 and FTC-238, respectively,
      compared to FTC-133; this finding was supported by immunohistochemistry results.
      TSH treatment did not alter FnR expression. From these studies, we conclude that
      invasive clones of FTC decrease their expression of FnRs without changing their
      expression of FN. Furthermore, TSH treatment may promote FN secretion by FTC-133,
      although it does not seem to affect FnR or absolute FN expression. The diminished
      expression of FnR adhesion plaques may enhance metastatic potential in some
      follicular thyroid cancers.

PMID- 7725747
TI  - Presymptomatic screening for medullary thyroid carcinoma in patients with
      multiple endocrine neoplasia type 2A.
AB  - Presymptomatic screening of medullary thyroid carcinoma in MEN IIA families
      enables the early diagnosis of this tumor with its significant morbidity.
      Biochemical screening consists of basal and stimulated serum calcitonin
      evaluation. Genetic screening is based on DNA analysis using linked DNA markers.
      Thyroidectomy at an occult tumor stage may be curative. Calcitonin measurement
      was carried out in 58 apparently unaffected family members at risk and 11 MEN IIA
      patients. Calcitonin elevation was detected in nine individuals. All nine
      underwent thyroidectomy. Histologic examination confirmed medullary thyroid
      carcinoma in eight patients and in one case C cell hyperplasia. Postoperatively,
      eight patients (89%) are clinically and biochemically tumor-free (mean follow-up
      30 months). DNA screening results in one affected family are presented. DNA
      analysis allowed recognition of one apparently unaffected individual at risk as a
      MEN IIA gene carrier. One family member at risk was found not to carry the gene
      and may be excluded from further screening.

PMID- 7725748
TI  - CD15 (LeuM1) immunoreactivity: prognostic factor for sporadic and hereditary
      medullary thyroid cancer? Study Group on Multiple Endocrine Neoplasia of Austria.
AB  - Patients treated for sporadic and hereditary medullary thyroid carcinoma (MTC)
      have varying rates of persistent disease, recurrence, and survival. The aim of
      this study was to correlate the immunoreactivity of the monoclonal antibody CD15
      (LeuM1) to initial clinical findings and the outcome of treatment. The primary
      tumors of 75 patients with sporadic MTC, 7 with hereditary disease, and 3 members
      of MEN 2A families were studied. Of these subjects 74 (87%) showed no or little
      immunoreactivity (< 15% positive cells; score 0) in most tumors. The remaining
      13% had surgery for tumors with more than 15% cells with positive staining (score
      I). There was no correlation between LeuM1 immunoreactivity and sex, age, and
      type of MTC. There was, however, a significant correlation with the pTNM
      classification and UICC staging. The prognosis for patients with score 0 was
      significantly better than score 1 patients. CD15 immunoreactivity appears to be a
      predictive factor in sporadic and hereditary MTC. Lymph node dissection seems to
      be more successful in patients with score 0 tumors than in those with score 1
      tumors. The question of reoperation in patients with recurrence of disease
      (especially with biochemical recurrence or persistence) should be discussed on
      the basis of CD15 immunoreactivity.

PMID- 7725749
TI  - Expression of calcitonin and somatostatin peptide and mRNA in medullary thyroid
      carcinoma.
AB  - We have studied a series of 22 human medullary carcinomas (MCTs), both primary
      and metastatic, using immunocytochemistry (ICC) to localize calcitonin and
      somatostatin peptide and in situ hybridization (ISH) to localize calcitonin and
      somatostatin mRNA. All tumors were positive for calcitonin peptide with ICC,
      which often showed considerable intercellular heterogeneity, with many cells
      having undetectable levels of calcitonin. However, calcitonin mRNA localized by
      ISH was much more uniformly distributed, indicating that MCT tumor cells may
      retain the capacity to both synthesize and store calcitonin, whereas others lose
      their storage but not their synthetic capacity. Somatostatin peptide and mRNA
      were found in tumors from 15 patients. In contrast to the pattern seen with
      calcitonin, somatostatin mRNA and peptide were usually found in single scattered
      cells. When correlation was possible, the same cell showed positivity for
      somatostatin mRNA on ISH and positivity for somatostatin peptide on ICC. However,
      in one tumor many more cells were positive for mRNA than for peptide, suggesting
      that only a proportion of cells retained the ability to store the peptide. The
      variation in cellular content of immunoreactive calcitonin is interpreted as
      resulting from either an increased tumor growth rate or reduced ability to store
      peptide in a less differentiated tumor. With somatostatin there was good
      correlation between mRNA and peptide content, but it occurred in single widely
      scattered cells, most tumor cells being negative for both peptide and mRNA. It is
      suggested that somatostatin production might be associated with a reduction in
      the growth of the cell concerned, either through a differentiation step or
      through a direct effect of the hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725751
TI  - Outcome of 309 patients with metastatic differentiated thyroid carcinoma treated
      with radioiodine.
AB  - From 1969 to 1990 there were 309 patients with differentiated thyroid carcinoma
      (241 papillary and 68 follicular) treated with radioactive iodine for functioning
      node metastases alone (n = 191) or distant metastases (n = 118) with or without
      node metastases. These patients represented 32.7% of 945 patients treated in our
      institution during the same period. Initial treatment included near-total
      thyroidectomy and 131I ablation of postsurgical thyroid residue, followed by L
      thyroxine suppressive therapy. At the end of follow-up (mean 5.8 years), 146
      patients (76.4%) in the group with nodal metastases were considered cured, as
      assessed by clinical and laboratory evaluation including whole body scan (WBS)
      and serum thyroglobulin (Tg) levels; 32 patients (16.7%) had persistent disease.
      Loss of 131I uptake in persistent metastatic lesions occurred in five patients
      (2.6%), and newly developed distant metastases occurred in eight patients (4.2%).
      Of the patients with distant metastases, 36.4% were cured by 131I. Distant
      metastases from papillary carcinomas had a higher cure rate than follicular
      carcinomas (p < 0.01). The metastases of four patients (5.2%) lost the property
      to take up radioiodine. Lung and bone metastases detectable by WBS but not by
      radiography were most likely to be cured by 131I. The overall survival at the end
      of follow-up was 95.8% in patients with only lymph node metastases and 76.0% in
      those with distant metastases. Tumor-related deaths were 3.6% and 23.7%,
      respectively. Our data indicate that 131I therapy is highly effective in the
      treatment of lymph node metastases from differentiated thyroid
      carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725750
TI  - Clinical course of metastatic parathyroid cancer.
AB  - In a retrospective study the clinical course of 40 patients with symptomatic
      persistent or recurrent parathyroid cancer was analyzed in order to assess the
      value of aggressive surgical intervention. Recurrence was diagnosed after a
      median period of 33 months (1-228 months). Twenty-two patients had locoregional
      disease, whereas 14 patients had both local and distant spread. The remaining
      four patients had distant spread. Patients with just locoregional disease were
      subject to one to nine reoperative procedures. The median survival time from the
      last operation was 39 months (1-204 months). Eight patients then had no evidence
      of disease, three were hypercalcemic and 9 of 11 had died of parathyroid cancer.
      Distant spread was demonstrated in 17 of 40 patients. Pulmonary metastases
      predominated (14 of 17). Surgical excision was performed in 9 of 14 cases. Of
      these nine, two patients had a subsequent disease-free interval of 36+ and 72+
      months, respectively. One patient was reported hypercalcemic after 84 months,
      whereas five patients died of cancer between 4 and 60 months after their last
      surgical exploration. One patient was lost to follow-up. In all, 21 patients
      (53%) died of parathyroid cancer. Conspicuous nuclear atypia and frequent mitoses
      predominated. Image cytometric DNA analysis showed high rates for all three
      groups (median p90 = 80%, range 21-98%).

PMID- 7725752
TI  - Parathyroid localization by catheterization of large cervical and mediastinal
      veins to determine serum concentrations of intact parathyroid hormone.
AB  - A success rate of about 90% has been achieved after primary operations for
      hyperparathyroidism, compared with 60% to 80% in most series of secondary
      operations. The present reoperative series involved 29 patients who underwent
      venous catheterization with blood sampling for the determination of intact
      parathyroid hormone before undergoing repeat parathyroid surgery. Blood samples
      were taken from the internal jugular veins, innominate veins, and superior caval
      vein. No attempt was made to perform superselective catheterization of the small
      neck and mediastinal veins. The reoperations were done by four surgeons who did
      1, 2, 13, and 13 of the reoperations, respectively. In all patients, distinct
      step-ups in parathyroid hormone concentrations were found. On average, the
      gradient between the highest and lowest value was about 5. Close to the location
      of the step-ups, diseased parathyroid tissue was found in 27 of the patients. In
      two cases no parathyroid tissue was found, and these patients remained
      hyperparathyroid postoperatively. They had been treated by the surgeon who did
      only two of the operations. When the step-up was observed in the left innominate
      vein, we could not differentiate mediastinal from low cervical adenomas. No
      patient developed hypoparathyroidism. To avoid this complication,
      autotransplantation of diseased parathyroid tissue into the abdominal
      subcutaneous fat was done in nine patients. No case of recurrent laryngeal nerve
      paralysis occurred. The introduction of reliable assays for the analysis of
      parathyroid hormone can make selective catheterization unnecessary when
      localizing remaining parathyroid glands in patients with persistent
      hyperparathyroidism.

PMID- 7725753
TI  - Surgery for sporadic primary hyperparathyroidism in the elderly.
AB  - Retrospective analysis has been performed on 108 consecutive patients operated
      for primary hyperparathyroidism (HPT) at 75 to 85 years of age (mean 79 years).
      The preoperative serum calcium value averaged 2.99 mM, and six patients had
      hypercalcemic crisis. Psychic disturbances were seen in 60 patients (56%), 40% of
      whom demonstrated dementia. Skeletal and muscular complaints were registered in
      29% and 19%, respectively, and only 6% were overtly asymptomatic. Cardiovascular
      diseases were presented by 69% of the patients, 13% had diabetes mellitus, and
      26% were institutionalized prior to surgery. Bilateral neck exploration disclosed
      a single adenoma in 69%, which was of the oxyphil cell type in 13%, and water
      clear (n = 3) or chief cell hyperplasia in 27%. The total glandular weight
      averaged 1085 mg. Altogether 72 patients operated on after 1980 demonstrated a
      perioperative (30-day) mortality of 1.4%; the corresponding morbidity of 8.7%
      mainly included infections as well as a vocal cord paralysis in one patient and
      two incisional hematomas. Analysis for mean 3.1 years postoperatively displayed
      reversal of hypercalcemia in 95% of the patients; 2.8% of those operated after
      1980 had persistent disease. Symptoms seemed to be alleviated in 62%, with a
      similar rate attained in patients with dementia. Altogether 60 patients died from
      mainly cardiovascular diseases mean 4.2 years after the operation. Those
      succumbing the first postoperative year (n = 21) showed overrepresentation of
      cardiac diseases and diabetes mellitus. The results demonstrate prevalent psychic
      disturbances, oxyphil adenomas, and multiglandular parathyroid disease in elderly
      patients with primary HPT and favor rather liberal application of parathyroid
      surgery among these individuals.

PMID- 7725754
TI  - Primary hyperparathyroidism and the heart: cardiac abnormalities correlated to
      clinical and biochemical data.
AB  - Comparing patients with primary hyperparathyroidism (PHP) to a normocalcemic
      control population, those with PHP have a higher incidence of cardiovascular
      disease and cardiac abnormalities. This study aimed at correlating cardiac
      findings (valvular and myocardial calcification, myocardial hypertrophy) with
      clinical data (age, sex, clinical manifestation, nephrolithiasis,
      nephrocalcinosis, hypertension, skeletal abnormalities, hypercalcemic syndrome)
      and biochemical data (serum calcium, serum phosphate, serum iPTH level, serum
      creatinine). A group of 132 consecutive patients with surgically verified PHP (94
      women, 38 men; ages 15-86, mean age 57 +/- 16 years) were included in this study.
      Blood chemistry, clinical presentation, radiography, and echocardiography were
      carried out in all patients for univariate and multivariate analyses of all
      parameters. There was no statistical correlation between clinical symptoms,
      biochemical data, and cardiac calcific alterations. Typical skeletal
      manifestations (osteolysis/subperiostal resorption) and valvular calcifications
      were significantly correlated to left ventricular hypertrophy (p = 0.005).
      Cardiac abnormalities such as calcific myocardial deposits or mitral and aortic
      valvular calcifications do not correlate with laboratory findings and clinical
      presentation at the time of diagnosis. There was no biochemical or clinical
      variable that could predict the frequency or severity of valvular sclerosis or
      calcific deposits in the myocardium. However, PHP-related skeletal abnormalities
      and valvular calcification were predicting factors for left ventricular
      hypertrophy, a reversible cardiac manifestation of PHP. Myocardial hypertrophy is
      more often found with classic symptomatic PHP with osseous abnormalities.

PMID- 7725755
TI  - Expression of proliferating cell nuclear antigens in parathyroid glands of renal
      hyperparathyroidism.
AB  - Total parathyroidectomy with autotransplantation of a small piece of the resected
      hyperplastic gland is currently the usual surgical procedure for renal
      hyperparathyroidism in Japan. Empirically, the smallest glands showing diffuse
      growth are selected for the graft. In order to seek the rationale for this
      procedure, we examined 50 cases of both nodular and diffuse hyperplastic
      parathyroid glands and five cases of recurrent grafted tissues histologically and
      immunohistochemically with anti-proliferating cell nuclear antigen (PCNA)
      antibody. The proliferative activity of the glands growing in diffuse fashion was
      much lower than that of those growing in nodular fashion (p < 0.05). All the
      parathyroid glands selected for grafting in the recurrent cases showed nodular
      growth. No relation was revealed between PCNA expression and the size of the
      glands, or between the former and the type of cell components (chief and
      oxyphilic cells). In nodular lesions, immunopositive cells were frequently
      distributed near the thick fibrous capsule. From these results, we conclude that
      parathyroid glands showing a diffuse growth pattern are indeed suitable for the
      graft. When only a nodular hyperplastic parathyroid gland is available, it is
      suggested that the central portion of the nodule may provide a better source for
      the graft with little change of recurrence.

PMID- 7725756
TI  - Successful allotransplantation of microencapsulated parathyroids in rats.
AB  - Allotransplantation of parathyroid tissue in humans is desirable for treating
      long-term hypoparathyroidism (e.g., after inadvertent removal of parathyroid
      glands during thyroid surgery). Until now, parathyroid allotransplantation was
      not used clinically because its advantages were outweighted by the need of
      immunosuppression. To overcome the immunogenicity of the tissue to be
      transplanted, we employed the method of microencapsulation; first tried in islet
      cell transplantation for experimental allotransplantation of parathyroid tissue.
      We have been able to achieve long-term success in a rat model. After isolation
      and tissue culture, tissue pieces from parathyroid glands of 280 Lewis rats were
      encapsulated in barium alginate and grafted into hypocalcemic DA rats. From the
      7th to the 90th day after transplantation the recipient rats (DA rats) showed a
      normal serum calcium concentration. This is the first report of successful long
      term survival and function of microencapsulated allotransplanted parathyroid
      tissue.

PMID- 7725757
TI  - The significance of electrogastrographically determined amplitudes--is there a
      correlation to sonographically measured antral mechanical contractions?
AB  - Cutaneous electrogastrography (EGG) allows the measurement of gastric electrical
      activity. An association of EGG with gastrointestinal motility disorders has been
      shown. Abnormalities of electrical rate or rhythm are accepted as the most
      important parameters in EGG. However, the reliability of the magnitude of
      electrical amplitude in the assessment of motility is discussed controversially.
      Therefore in a prospective study we investigated the relation between amplitude
      and antral contractions by means of ultrasonography. 8 healthy volunteers (4 men,
      4 women, 24-31 years) ingested 400 ml carbonated mineral water after an overnight
      fast at two separate study days. Over a period of 10 min preprandial and 10 min
      postprandial small and intense antral contractions were measured employing
      sagittal antral planimetry. Simultaneous amplitudes were determined during
      contractions and at 1 min intervals (average amplitude) by cutaneous
      electrogastrography. Data were analyzed by Wilcoxon's rank sum test and Spearman
      rank correlation test. The coefficient of variation of the
      postprandial/preprandial amplitude ratio was nearly two times greater between
      subjects than between recordings in the same subject, which reflects a moderate
      intraindividual reproducibility. We found a significant increase in the average
      amplitude postprandially (p < 0.05). Although postprandial contractions (n = 243)
      predominated preprandial contractions (n = 127) significantly (p = 0.02), no
      significant correlation between the number of contractions and the average
      amplitude existed (R = 0.1; p = 0.7). Moreover the average amplitude did not
      differ from amplitudes during intense and small contractions significantly (p =
      0.7; p = 0.1). The magnitude of the amplitude measured by EGG does not correlate
      with the mechanical gastral activity significantly.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7725758
TI  - [Clip migration in the common bile duct and consecutive calculus formation after
      laparoscopic cholecystectomy].
AB  - In 1991 a 64-year old woman underwent laparoscopic cholecystectomy for
      symptomatic gallstones. The follow-up was uneventful. Two years later a painless
      obstructive jaundice appeared. Endoscopic retrograde cholangio-pancreatography
      revealed a freely floating surgical clip within the common bile duct. It was a
      FILSHIE-Clip, commonly used to ligate the cystic duct. The endoscopic extraction
      of the foreign body was unsuccessful because the clip slipped into a small
      intrahepatic bile duct. Smaller gallstones that had probably crystallized around
      the clip could be extracted. Finally the clip itself disappeared spontaneously
      after endoscopic sphincterotomy through the papilla. It is discussed why movement
      of a surgical clip into the common bile duct appears after laparoscopic
      cholecystectomy.

PMID- 7725759
TI  - [Villous rectal adenomas and secretory diarrhea].
AB  - Hypersecretion following villous adenomatosis of the rectum is demonstrated by
      two single case studies. Both patients exhibited a secretory diarrhea with a
      2.000-2.500 and 1.000 ml daily stool volume respectively, resulting in severe and
      life-threatening (first patient) loss of water and electrolytes. With increasing
      stool volume, rising concentrations of Na and Cl were observed in the stool and
      approached plasma levels. Consecutively the potassium concentration decreased to
      values between 15 and 23.4 mmol/l in the first severe case and to 28 and 31
      mmol/l in the patient with the lowest stool volume. Elevated PG-E2 concentrations
      in the fluid moiety of the stool (up to 13.3 ng/ml and 0.98 ng/ml respectively)
      as well as the response to treatment with Indomethacin support the idea of a PG
      E2 induced pathological loss of water and electrolytes. While 100 mg
      Indomethacin/day led to cessation of symptoms in the less severe case, even 400
      mg Indomethacin/day were not able to reduce the massive rectal water loss in the
      first most severe patient to less than 1,000 ml/day. Surgical removal of villous
      adenoma showing hypersecretory activity is the only promising therapy. In case of
      inoperability, denial of surgical intervention or just for palliative treatment
      prior to surgery we recommend the inhibition of PG-synthesis with Indomethacin.

PMID- 7725760
TI  - [Antibiotic therapy of primary MALT stomach lymphomas--have surgery and radiation
      been replaced?].

PMID- 7725762
TI  - Relationships between the degree of Helicobacter pylori colonisation and the
      degree and activity of gastritis, surface epithelial degeneration and mucus
      secretion.
AB  - This study investigates the question as to whether, in Helicobacter pylori (H.p.)
      gastritis, any statistically significant relationships are to be found between
      the following histological parameters: degree of H.p. colonisation, the degree
      and activity of gastritis, degree of replacement of the foveolar epithelium by
      regenerating epithelium, and degree of mucus depletion. Forceps biopsy material
      obtained from 240 patients with NUD and H.p. gastritis (3 specimens from the
      antrum, 2 from the corpus) were investigated. The 5 histological parameters
      employed were graduated semiquantitatively as follows: 0 = normal findings, 1 =
      minimal, 2 = low-grade, 3 = medium-grade, 4 = high-grade. The evaluation showed
      that the degree and activity of gastritis, the degree of replacement of foveolar
      epithelium by regenerating epithelial cells, and the degree of mucus depletion
      are dependent upon the degree of H.p. colonisation (p < 0.0001). The gastritis
      parameters were more marked in the antrum than in the corpus. The
      intercorrelations were highly significant for all five parameters investigated,
      both in the antrum and corpus (p < 0.0001). On the basis of these results it is
      concluded that for the histological assessment of H.p. gastritis, in addition to
      H.p. colonisation, and the degree and activity of gastritis, but also the state
      of the foveolar epithelium and the mucus production of these epithelial cells
      should be considered.

PMID- 7725761
TI  - [Mutations of the hMSH2 and hMlH1 genes are responsible for 90% of hereditary
      colorectal carcinomas].

PMID- 7725764
TI  - [Fetal development in mild and severe pre-eclampsia: correlation with maternal
      laboratory parameters and Doppler ultrasound].
AB  - During three and a half years we observed 83 single pregnancies all delivered by
      caesarean section. All of them had a mild (systolic blood pressure > 140,
      diastolic > 90 and proteinuria > 0.5 g/dl) or a severe preeclampsia (systolic
      blood pressure > 160, diastolic > 100 and proteinuria > 3.0 g/dl). We found
      significantly twice as many abnormal uteroplacental blood flow velocities in the
      severe preeclampsia group than in the mild one. These results draw us to the
      conclusion that possible pathological changing of the vessels is due to
      preeclampsia which does not need to correlate with a placental insufficiency and
      fetal growth retardation. An abnormal uteroplacental blood flow velocity
      connected with an abnormal umbilical blood flow velocity raises the fetal
      morbidity and the early childhood morbidity. Fetal outcome in mild compared to
      severe preeclampsia definitively shows a worse prognosis for those fetuses whose
      mother developed a prepartal severe preeclampsia. A distinctly increased rate of
      cerebral haemorrhages, abnormal neurological signs, acute respiratory distress
      syndromes and bronchopulmonary dysplasia was found. Finally we show an additional
      risk for fetal outcome in absent or reverse enddiastolic flow velocity (AREDFV)
      in the severe preeclampsia group. We observed in the AREDFV group with severe
      preeclampsia in comparison to a group of AREDFV without maternal preeclampsia
      more than twice as many cerebral haemorrhages, abnormal neurological signs and
      bronchopulmonary dysplasia.

PMID- 7725765
TI  - [Transvaginal Doppler ultrasound in early pregnancy--normal values and comparison
      with a risk sample with threatened abortion].
AB  - In the study introduced here, norm values for embryo-feto-placental circulation
      are illustrated. The values were gained by examining 75 singleton pregnancies of
      uncomplicated course and ending with non-problematic birth of an eutrophic child.
      In addition to qualitative parameters such as A/B-ratio and Pulsatility Index,
      the maximum systolic frequency shift was measured by transvaginal Doppler
      sonography between the fifth and 24th week of gestation (post menstruation), to
      obtain another quantitative parameter. The increasing circulation can be
      impressively visualized by viewing the corresponding norm value curves. This is
      valid for both the embryo-fetal as well as maternal side of the placenta. Over
      the same time period, 53 high-risk pregnancies with symptoms of premature labor
      were followed to enable comparison with the circulatory changes in normal
      pregnancy. It was not possible to differentiate normal and abnormal pregnancy
      regarding premature labor by examining the utero-feto-placental unit with
      transvaginal Doppler sonography. In direct comparison, the Doppler values showed
      no significant differences. The norm curves introduced in this study should be
      considered as a basis to evaluate the utero-feto-placental circulatory system
      using Doppler sonography and be of use to differentiate abnormal changes of
      perfusion during the course of pregnancy, soby making it possible to recognize a
      pregnancy at risk early on.

PMID- 7725766
TI  - [Cerebral Doppler ultrasound in fetal hydrocephalus].
AB  - Within a six-year period (1988-1993), we diagnosed and treated 143 cases of fetal
      hydrocephalus. We investigated the relationship between the degree of dilatation
      of the cerebral ventricles, the thickness of the pallium, and blood flow
      velocities in cerebral arteries. The assumption that progressive dilatation of
      the fetal ventricles leads to increasing resistance of the cerebral blood flow
      and disrupted cerebral perfusion was confirmed. Applying the postnatal pediatric
      principle of indication for shunt implantation based on Doppler sonographic
      diagnosis, delivery was instituted immediately in cases with pathologically
      increased pulsatility indices (PI). In all cases, this indication and the need
      for immediate shunt implantation were confirmed by postnatal pediatric
      ultrasonography. Cerebral Doppler velocimetry enables timely identification of
      fetuses at risk for pressure- or ischemia-induced cerebral tissue damage. The
      timing of delivery and subsequent neurosurgical therapy can thus be optimized.

PMID- 7725763
TI  - [Re-treatment with interferon-alpha in chronic hepatitis B and C virus
      infection].
AB  - The efficacy of interferon-alpha retreatment was assessed in patients with
      chronic hepatitis B or C, not responding to a first cycle of interferon or
      reactivating thereafter. 27 patients with chronic hepatitis B and 25 patients
      with chronic hepatitis C were investigated. After an interval of at least 6
      months these patients received an interferon-alpha retreatment in a higher dosage
      schedule and with a different interferon-alpha subtype. In patients with chronic
      hepatitis B a loss of serum HBV-DNA was observed in 59% patients after interferon
      alpha retreatment. HBeAg seroconversion occurred in 8 of these patients. In
      chronic hepatitis C 32% of the patients responded completely to the second cycle
      of interferon-alpha treatment with a normalization of ALT associated with a loss
      of serum HCV-RNA. A partial response with a marked reduction of ALT was seen in 4
      patients. In chronic hepatitis B and C a complete or partial response to the
      retreatment was closely associated with the response status after the first
      cycle. Thus, interferon retreatment seems to be effective in patients with
      chronic hepatitis B or C, especially in the subgroup of patients exhibiting a
      partial or complete response after the first interferon treatment.

PMID- 7725767
TI  - [Induced labor with prostaglandins: 0.5 mg PGE2 intracervical gel versus 3 mg
      PGE2 vaginal tablet].
AB  - For the induction of labour prostaglandin (PG) E2 has been recommended either as
      intracervical gel (0.5 mg) or as vaginal tablet (3 mg) depending on the Bishop
      score of the cervix. A prospective trial was conducted in 79, mainly postterm,
      pregnancies (59 with a Bishop score < 5), in whom either PG-E2 tablet or gel was
      given randomly without respect to the cervical score. In addition, 51 inductions
      in primiparous women (44 with a Bishop score < 5) were analysed retrospectively.
      In pregnancies with a Bishop score < 5 the rate of successful inductions,
      duration of labour or incidence of neonatal acidosis was not different in both
      groups. Similar results were obtained in the prospective trial for inductions
      with a cervical score > 4. These data suggest the lack of superiority of the
      intracervical over the vaginal route of PG-E2 administration for the induction of
      labour.

PMID- 7725768
TI  - [Is a generalized amalgam ban justified? Studies of mothers and their newborn
      infants].
AB  - To measure the Hg-contamination from amalgam as well as other exposures to
      mothers and their newborns 185 women with tooth filling surfaces from 0 to 780
      mm2 were examined. The Hg-values of mother and child at a time showed a highly
      significant correlation with a median value from 0.4 resp. 0.5 microgram/Hg/l.
      Obviously, the placenta has a retention capability with up to 10 times higher Hg
      values and a low positive correlation to the amalgam surfaces. There was no
      relationship between the blood values of the women and the children and the size
      of the surfaces of the amalgam fillings. Opposite to this a high consumption of
      fish led to higher Hg-values in the umbilical cord blood, this even in children
      with mothers without amalgam fillings. Other exposures through working conditions
      (i.e. dental assistant) or living environment did not lead to higher values.
      Symptoms of diseases such as headaches, allergies, eczemas appeared with those
      patients who had amalgam fillings as well as those in the group without amalgam
      fillings. All women gave birth to healthy children. With all necessary caution
      concerning contamination with heavy metals during pregnancy some of today's panic
      inducing portrayals do not seem justified.

PMID- 7725769
TI  - [Prenatal diagnosis of hypoplastic left heart syndrome--indications for abortion
      or transplantation?].
AB  - Early diagnosis of fetal cardiac malformations in center of Perinatal Medicine is
      now possible with the use of modern high frequency ultrasound technics in
      combination with the 3-step-program of the DEGUM. The diagnosis of most cardiac
      malformations can early already be obtained in the 2nd trimester as for example
      the lethal hypoplastic left ventricle syndrome. We want to discuss the problem of
      prenatal diagnosis of the hypoplastic left heart syndrome and the possibilities
      of therapeutic procedures.

PMID- 7725770
TI  - [Blood flow profile in the uterine artery. Correlation with placental morphology
      and clinico-obstetrical data within the scope of pre-eclampsia].
AB  - Within a group of preeclamptic women we found severe histologic placental
      pathology with functional relevance when both the uteroplacental and
      fetoplacental flow velocity waveforms showed elevated resistance indices. These
      pathological findings were a reduced decidual area, infarction and villus
      maturation failures with a high rate of intrauterine growth retardation, acidosis
      and premature delivery. In cases with normal flow velocity waveforms these
      pathologic findings were much rarer although the patients were preeclamptic, too.

PMID- 7725771
TI  - [Theses of papers presented at the 3rd (XVI) meeting of the Physiological Society
      of the Russian Academy of Sciences].

PMID- 7725772
TI  - Reversal of atherosclerotic obstructions by percutaneous transluminal angioplasty
      raises high-density lipoprotein cholesterol.
AB  - Variation of high-density lipoprotein cholesterol (HDL) levels in man show a
      strong inverse relationship to the incidence of atherosclerotic vascular disease.
      Conversely, effects of atherosclerosis and ischemia on lipoprotein metabolism are
      unclear. We investigated 41 patients, 10 women and 31 men, undergoing
      percutaneous transluminal angioplasty by measuring fasting lipoprotein
      cholesterol including high-density lipoprotein subfraction analysis before and
      one as well as 12 weeks after the procedure. Successful reopening of a
      haemodynamically significant iliac, femoral or popliteal obstruction was achieved
      in all patients. A highly significant (p < 0.001) increase of HDL cholesterol
      from 1.10 +/- 0.05 to 1.31 +/- 0.06 mmol/l was revealed 12 weeks later. This was
      due to a significant (p < 0.001) increase in HDL3 cholesterol by 26%, whereas
      HDL2 cholesterol did not change significantly. We conclude that HDL cholesterol
      levels increase after recanalization of a significant atherosclerotic obstruction
      which may be a direct effect of reperfusion or an indirect effect due to an
      increase in exercise tolerance.

PMID- 7725773
TI  - Influx of antibiotics into diabetic legs with plantar ulcerations: regional and
      systemic Netilmycin levels compared after retrograde-venous and systemic-venous
      application.
AB  - Retrograde venous perfusions (RVP) of antibiotics were proven to be
      therapeutically more effective than systemic venous infusions (SVI) in patients
      with infected diabetic neuropathic plantar ulcers (DNPU: no additional
      macronagiopathy of leg arteries). In order to study some pharmakokinetic features
      of RVP application paratibial tissue levels of Netilmycin (NL; from suction
      blister fluid) and cubital venous NL were compared under each SVI and RVP therapy
      in 8 patients with DNPU. Tissue (11.6 +/- 6.4 micrograms/l) were significantly
      higher (p < 0.001) an within the therapeutic range after RVP (SVI: 4.31 +/-
      1.68). In ulcer transsudate (RVP only; n = 4) NL mounted to 36.4 +/- 11.6
      microgram/ml. Peak and base NL in cubital blood were within the normal range for
      both SVI and RVP (no significant difference). The date indicate that RVP is
      superior to SVI application of Netilmycin (and probably other antibiotics) as
      surmounting the damaged microcirculation in DNPU to achieve effective drug levels
      in the target tissue.

PMID- 7725774
TI  - Biochemical monitoring in patients during revascularization surgery.
AB  - Changes in the metabolism of patients with peripheral arterial occlusive disease
      were studied in the light of biochemical parameters during and after vascular
      reconstructive surgery (aorto-bifemoral bypass). Biochemical parameters were
      determined in arterial and regional venous blood in 10 successive intervals
      covering the period before ischemia, during acute ischemia and in the course of
      reperfusion of the lower extremity. After successful revascularization of the
      extremity, marked increases were recorded particularly in the levels of
      thiobarbituric acid reactive substances and of lactate in the early and late
      period of reperfusion. Monitoring of the given biochemical parameters may yield
      an adequate criterion for determining the degree of ischemia-reperfusion injury
      in vascular reconstructive surgery and may also be of value in assessing the
      effectivity of the applied mode of protecting the patient against functional and
      metabolic injury.

PMID- 7725775
TI  - Surgical aspects of popliteal artery entrapment syndrome: 26 years of experience
      with 26 legs.
AB  - The authors present their experience in diagnosis, therapy and follow up of the
      Popliteal Artery Entrapment Syndrome (PAES) during the last 26 years. PAES
      appears most frequently in young athletic male patients. From 1967 to 1993, 20
      patients, 17 male (85%) and 3 female (15%), with 26 entrapment legs were treated.
      Average age at the time of the first symptoms was 33.5 years and at the time of
      diagnosis 38.5 years. Six patients suffered from PAES on both legs. In 5 of the
      24 operated cases a re-operation was necessary. One case required a third
      operation. To reduce the postoperative complication rate, surgical technique was
      chosen according to the anatomical situation. If there was only slight disease of
      the popliteal wall, the current surgical technique consisted in decompressing the
      artery and replacing it in the orthotopic position through a direct entrance with
      the patient in the prone position. If there was severe disease of the popliteal
      wall, an autologous venous bypass from the popliteal artery segment I to segment
      III should be done with the patient supine. In our opinion, a primary catheter
      lysis therapy, which can be indicated for stenosed arteries, should not be done
      for peristenotic aneurysms. Successful therapy of PAES largely depends on early
      diagnosis that has been confirmed by CT scan.

PMID- 7725776
TI  - [Responsibilities of academic vascular surgery: (between mechanics and ideas-
      from routine to ultimate management)].

PMID- 7725777
TI  - Partial interruption of the inferior vena cava: ten-year evolution in protocols
      at Grenoble University Hospital. Study of 621 patients.
AB  - An evolution in protocols regarding indications and modalities for Partial
      Interruption of the Inferior Vena Cava (PIIVC) on 621 patients at Grenoble
      University Hospital is reported and the influence of new methods in diagnosis
      (vascular sonography) and therapy (percutaneous filters) is assessed. This
      comparative study covers the intervals from 1982-1984 (Period A - 333 patients),
      and 1989-1991 (Period B - 288 patients). The percentage of patients with venous
      thromboembolic disease who underwent PIIVC clearly decreased (21.8% in period A
      vs. 13% in period B, p < 0.01). The incidence of what are currently miscalled
      "prophylactic", but are in fact adjunctive indications also diminished (115
      patients in period A, or 34.5% of the PIIVC cases vs. 60 patients in period B, or
      20.8% of the PIIVC cases, p < 0.05). There was a reduction in the use of Miles
      caval clips (59 patients or 17.7% for period A vs. 34 patients or 11.8% for
      period B, p < 0.05). Although there has been an increase in the use of
      percutaneous caval filters, the use of percutaneous filters has not lead to an
      increase in the real rate of PIIVC performed by an Angiology Unit with a large
      experience in the diagnosis and follow-up of patients with venous thromboembolic
      disease.

PMID- 7725778
TI  - Comparison of long-term survival after repair of ruptured and non-ruptured
      abdominal aortic aneurysm.
AB  - Late survival rates were compared and analysed for 1070 patients undergoing
      repair of ruptured infrarenal abdominal aortic aneurysm (RAAA, n = 364, mean age
      70.0 years, male:female ratio 5.6:1) and non-ruptured abdominal aortic aneurysm
      (AAA, n = 706, mean age 66.6 years, male: female ratio 5.4:1) between January
      1970 and July 1992 at the Department of Thoracic and Cardiovascular Surgery of
      Helsinki University Central Hospital, Finland. There was a statistically
      significant difference in survival rates between the RAAA and AAA groups during
      the first three months after repair of abdominal aortic aneurysm. Operative
      mortality rates were 7.4% for electively repaired abdominal aortic aneurysms and
      48.7% for ruptured abdominal aortic aneurysms. For 3-month postoperative
      survivors there existed no statistically significant difference in late survival
      rates, nor did these rates differ from those of an age- and sex-matched
      population. Five-year survival rates for 3-month postoperative survivors were 60%
      in the RAAA group and 67% in the AAA group. Median survival time was 5.7 years
      and 7.5 years, respectively. Coronary artery disease, hypertension, chronic
      obstructive pulmonary disease and renal insufficiency statistically significantly
      reduced late survival rates after 3 months post-surgery for non-ruptured
      abdominal aortic aneurysm, whereas these risk factors did not alter late
      prognosis after successful repair of ruptured abdominal aortic aneurysm.
      Cerebrovascular disease reduced late survival rates both in AAA (median survival
      time 6.3 years) and RAAA group (median survival time 4.9 years). Of late deaths
      41% were caused by coronary artery disease in the AAA group and 38% in the RAAA
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725779
TI  - [Chronic critical leg ischemia: revascularization of the isolated popliteal
      segment in comparison with femoro-distal bypass].
AB  - Several patients with chronic critical limb ischemia show angiographically an
      isolated popliteal segment (IPS) and a single calf vessel (SCV) with no direct
      communication to the former. In this situation a bypass can be inserted from the
      common femoral artery to the IPS or to the SCV. The results of 73 bypass
      procedures--40 to an isolated popliteal segment and 33 to a single calf vessel
      for limb salvage--were prospectively evaluated. Eighty percent of the grafts were
      performed with an autogenous saphenous vein (ASV), the rest with a thin wall
      polytetrafluoroethylene (PTFE) prosthesis. The mean age of our patients was 75
      years and many suffered from cardiovascular disease. The operative mortality rate
      was 3% and the mean postoperative survival 32 months. Three year patency and limb
      salvage rates for ASV grafts was 83% and 87% (IPS) respectively 77% and 76%
      (MCV); for PTFE grafts 58% and 88% (IPS) respectively 17% and 50% (MCV). There
      was no significant difference found in patency and limb salvage rates of the two
      procedures if the graft was an autogenous saphenous vein (p > 0.05). The PTFE
      prosthesis was only suitable for grafts inserted to the isolated popliteal
      segment.

PMID- 7725780
TI  - The effect of forskolin on blood flow, platelet metabolism, aggregation and ATP
      release.
AB  - Forskolin, a diterpene obtained from coleus forskolii, is a potent cAMP
      stimulator. We have evaluated the effects of forskolin on blood flow, platelet
      aggregation and metabolism. It was found that forskolin has a dose dependent vaso
      relaxing effect in an in vivo sheep model, when infused intra-arterially.
      Furthermore forskolin, in a dose-dependent fashion reduced whole blood platelet
      aggregation and ATP release. Pretreatment of PTFE grafts with Forskolin
      significantly reduced platelet consumption 3 hours postoperatively and on the
      first postoperative day. The overall platelet metabolism, measured by a
      microcalorimetric technique after treatment with forskolin in vitro and ex-vivo
      postoperatively was significantly increased. IN CONCLUSION: Forskolin affects
      blood flow and platelet parameters favourably in the setting of occlusive
      arterial disease and reconstructive arterial surgery.

PMID- 7725781
TI  - [Aneurysm of the descending thoracic aorta in tertiary syphilis].
AB  - A 53-year-old female presented with septicaemia caused by left ureteric
      obstruction due to ureterolithiasis. Further diagnostic work-up for left
      mediastinal widening revealed an asymptomatic aneurysm of the descending aorta.
      Serologic tests for syphilis were highly positive (TPHA 1:10240, 19s-IgM-FTA-Abs
      1:20, Cardiolipin KBR 1:72 IU/ml). After a three weeks course of Penicillin G,
      19s-IgM-FTA-Abs was negative. A successful tube resection of the aneurysm was
      performed. The diagnosis of luetic aneurysm of the descending aorta was confirmed
      histologically. Although rare today, tertiary syphilis should be considered in
      the differential diagnosis of thoracic aneurysm in middle-aged patients lacking
      classical risk factors for atherosclerosis. The immune pathogenesis of
      cardiovascular syphilis still remains subject of controversy.

PMID- 7725782
TI  - Faecaloid breath heralding secondary aorto-enteric fistula.
AB  - A patient underwent simultaneous abdominal aortic prosthetic replacement and
      resection of a Meckel diverticulum. He then developed faecaloid breath. Later
      reoperation for aorto-enteric fistula cured halitosis. We conclude in retrospect
      that faecaloid breath may herald a secondary aorto-enteric fistula. A
      pathophysiological mechanism is suggested and discussed.

PMID- 7725783
TI  - [Left internal thoracic artery as a collateral vessel in chronic occlusion of the
      pelvic artery].
AB  - Four years after implantation of an aorto-bi-iliac artery graft, a 53-year-old
      man suffered from intermittent claudication with a walking distance of 50 meters.
      By transaxillary aortography the left femoral artery could not be visualized.
      Selective angiography of the internal thoracic artery revealed a collateral
      circulation from the subclavian artery via the left internal thoracic artery, the
      superior epigastric artery and the inferior epigastric artery into the left
      external iliac artery (Winslow's pathway). Prior to using the internal thoracic
      artery for coronary bypass surgery, a function of this vessel as a collateral to
      the lower extremities should be excluded.

PMID- 7725784
TI  - [Differential diagnosis of arm swelling after dialysis shunt surgery].

PMID- 7725785
TI  - Atherosclerosis of the visceral arteries.
AB  - Thrombosis in the visceral arteries is the most common cause of acute mesenteric
      ischemia. It typically occurs in areas of atherosclerotic narrowing.
      Atherosclerosis of splanchnic blood vessels also causes chronic mesenteric
      ischemia. In the present study, the occurrence of atherosclerosis in the celiac
      and mesenteric arteries was evaluated in an unselected Finnish autopsy series of
      120 patients. Thirty-five patients (29%) had stenosis in the first few
      centimetres of mesenteric arteries. In 18 cases (15%) at least two mesenteric
      arteries were stenotic. The celiac artery was the most common site of mesenteric
      artery stenosis. More distally, only hemodynamically insignificant signs of
      macroscopic atherosclerosis, fatty streaks or fibrous plaques, observed. The
      occurrence of mesenteric artery stenosis was strongly associated with aging.
      Sixty-seven per cent of the subjects aged 80 or more presented with mesenteric
      artery stenosis, whereas the rate was 6% among those aged less than 40 years.
      Despite sometimes extensive stenotic alterations in the mesenteric arteries, only
      one patient in our study had bowel necrosis at autopsy. We conclude that
      atherosclerosis of mesenteric arteries commonly affects individuals of advanced
      age. As a part of general arteriosclerotic process of the circulatory system,
      mesenteric artery atherosclerosis is strongly associated with atherosclerosis in
      coronary arteries. In addition, there was an association between atherosclerosis
      in mesenteric arteries and cerebral arteries in the skull base. Thus, a
      characteristic triad of postprandial abdominal pain, food aversion, and weight
      loss in an elderly patient with other manifestations of arteriosclerosis should
      suggest a possibility of the visceral arterial insufficiency.

PMID- 7725787
TI  - [The ecological concept of parasitism].
AB  - Analysis of morpho-ecological adaptations of parasites showed that their
      necessary and sufficient characteristic is their inhabiting the host environment.
      Integration with the environment is achieved 1) by adaptations towards a
      particular habitat (first order environment) at certain phases of ontogenesis,
      and 2) by adaptations to the aggregate of hosts, their ecology and factors
      regulating the numbers of parasites (second order environment) at the level of
      their entire life cycle. The evolutionary progress of parasites is sustained by
      the increase in their independence from extrinsic factors not by means of general
      organization complication and integration (as in free-living animals), but by
      elimination of free-living developmental stages and by increase of integration
      with the host environment. The basis of the latter is formed by ecological
      adjusting of parasites to the environment. It is achieved by syncytial
      transformation of the covers and the use of communication means analogous to
      those of host cells. The consequence of host-parasite integration is the
      transition of parasites from resource consumption to the "management" of the
      environment. It is manifested by their influence on defensive reactions and other
      functions of the organism, as well as on its behavior and ecology. Parasitism may
      turn into other forms of coexistence (commensalism, mutualism) in the course of
      coevolution, as a result of dialectical overcoming of antagonistic interactions
      of the two partners.

PMID- 7725786
TI  - [The chemical interaction of tadpoles of the frog Rana arvalis Nilss. with
      conspecific and heterospecific anuran tadpoles].
AB  - In double-choice experiments the tadpoles of Rana arvalis were offered chemical
      cues of con- and heterospecific tadpoles in different combinations. It was shown
      that they are capable of distinguishing these signals. The cues of Bufo bufo and
      Rana lessonae larvae induced a clear reaction of attraction, whereas those of
      Rana temporaria did not cause any visible behavioral response. Conspecific
      tadpoles were more attractive than clear water, irrespective of their
      relationship with the recipients, however, kin chemical signals were more
      preferable than those from non-relatives.

PMID- 7725788
TI  - [The genetic differentiation of mammalian taxa: their assessment by biochemical
      genetic markers].
AB  - A review of data on genetic differentiation of mammalian taxa has been made on
      the basis of estimating the percent of fixed gene differences (PFD). The results
      substantiate the existence of evident differences in the scale of genetic
      divergence between taxa in different mammalian orders. Among smaller mammals
      (marsupials, insectivores, chiropterans, myomorph and sciuromorph rodents,
      african mole rats, and elephant shrews) interspecific differences within a genus
      involve the average of 25-40% of investigated loci. At the genetic level the
      value is 50-60%, whereas at the familial level the differences are beyond the
      resolution capacity of the method (PFD = 60-80%). Orders of larger mammals can be
      divided into two subgroups. One of them that includes carnivores, artiodactylans,
      and hystricomorph rodents is characterised by PFD values of 10-14%, 30-50%, and
      69-70% at respective levels. The other subgroup composed of proboscideans,
      primates, pinnipeds, and toothed whales, has a low level of genetic divergence
      expressed by PFD values of 0-3%, 7-36%, and 50-60% at species, generic and
      familial levels, respectively. Insufficiency of data on baleen whales and
      perissodactyls does not allow to cluster them ultimately with any of these
      groups. There are three possible, but not necessarily alternative, causes for the
      observed differences in genetic divergence: 1) over-ranking of genera in larger
      mammals; 2) different paleontological age of orders; 3) unequal rates of
      molecular evolution.

PMID- 7725789
TI  - Genome renewal: a new phenomenon revealed from a genetic study of 43 strains of
      Saccharomyces cerevisiae derived from natural fermentation of grape musts.
AB  - We have analyzed by genetic means 43 strains of Saccharomyces that had been
      isolated from fermenting grape musts in Italy. Twenty eight of these strains were
      isolated from 28 cellars in the Region of Emilia Romagna. The other 15 strains
      came from 5 fermentations at four cellars near the city of Arpino, which is
      located south and east of Rome. We found that 20 of the 28 strains from Emilia
      Romagna were heterozygous at from one to seven loci. The balance were, within the
      limits of our detection, completely homozygous. All these strains appeared to be
      diploid and most were homozygous for the homothallism gene (HO/HO). Spore
      viability varied greatly between the different strains and showed an inverse
      relation with the degree of heterozygosity. Several of the strains, and in
      particular those from Arpino, yielded asci that came from genetically different
      cells. These different cells could be interpreted to have arisen from a
      heterozygote that had sporulated and, because of the HO gene, yielded homozygous
      diploid spore clones. We propose that natural wine yeast strains can undergo such
      changes and thereby change a multiple heterozygote into completely homozygous
      diploids, some of which may replace the original heterozygous diploid. We call
      this process 'genome renewal'.

PMID- 7725790
TI  - Respiratory inhibitors affect incorporation of glucose into Saccharomyces
      cerevisiae cells, but not the activity of glucose transport.
AB  - Incubation of starved galactose-grown S. cerevisiae cells with cyanide reduced
      glucose uptake as measured over a 5-s period. The Vmax for glucose uptake was
      decreased by over a factor of two but the apparent affinity for glucose doubled.
      When measured in the sub-second time scale, however, there was no significant
      inhibition of glucose uptake, by cyanide, up to 200-ms, clearly demonstrating
      that, in cyanide treated cells, glucose uptake was not linear for the first 5-s.
      After a 200-ms exposure of untreated cells to radio-labelled glucose, less than
      10% of the intracellular label resided in soluble uncharged compounds. In cyanide
      treated cells up to 43% of the labelled compounds were uncharged, with a
      concurrent reduction of intracellular label residing in anionic compounds. The
      results suggest that, in the presence of 10 mM cyanide when respiration is
      inhibited, a reduction in the cellular ATP concentration causes a reduction in
      hexose-kinase activity which results in an accumulation of internal free glucose,
      which in turn causes a reduction in net glucose transport.

PMID- 7725791
TI  - Consideration of the evolution of the Saccharomyces cerevisiae MEL gene family on
      the basis of the nucleotide sequences of the genes and their flanking regions.
AB  - Analysis of the DNA sequences of new members of the Saccharomyces cerevisiae MEL1
      MEL10 gene family showed high homology between the members. The MEL gene family,
      alpha-galactosidase-coding sequences, have diverged into two groups; one
      consisting of MEL1 and MEL2 and the other of MEL3-MEL10. In two S. cerevisiae
      strains containing five or seven MEL genes each, all the genes are nearly
      identical, suggesting very rapid distribution of the gene to separate
      chromosomes. The sequence homology and the abrupt change to sequence
      heterogeneity at the centromere-proximal 3' end of the MEL genes suggest that the
      distribution of the genes to new chromosomal locations has occurred partly by
      reciprocal recombination at solo delta sequences. We identified a new open
      reading frame sufficient to code for a 554 amino acid long protein of unknown
      function. The new open reading frame (Accession number Z37509) is located in the
      3' non-coding region of MEL3-MEL10 genes in opposite orientation to the MEL genes
      (Accession numbers Z37508, Z37510, Z37511). Northern analysis of total RNA showed
      no hybridization to a homologous probe, suggesting that the gene is not expressed
      efficiently if at all.

PMID- 7725792
TI  - Increase in copy number of an integrated vector during continuous culture of
      Hansenula polymorpha expressing functional human haemoglobin.
AB  - Recombinant human haemoglobin A (rHbA) was produced by a leucine-requiring strain
      of Hansenula polymorpha which had been transformed with an integration vector
      containing the Saccharomyces cerevisiae LEU2 gene and cDNAs for the expression of
      alpha and beta globin each driven by the H. polymorpha MOX promoter. After 40
      generations in a chemostat it was found that the integrated vector had become
      amplified in the host strain. In some cases this led to an increase in LEU2 gene
      dosage, but a loss of globin expression cassettes. In other cases the globin gene
      dosage also increased. These changes coincided with an increase in rHbA
      production in the culture, which was reversed when the dilution rate was
      increased. Isolates from a chemostat culture producing elevated levels of rHbA
      were grown in fed-batch fermentations, resulting in higher productivities than
      when inoculated with the parent strain. The rHbA produced was purified and
      characterized. Oxygen binding studies and electrospray mass spectrometry showed
      that the rHbA had been processed and assembled correctly, and behaved as a fully
      functional co-operative tetramer.

PMID- 7725793
TI  - The nucleotide sequence and initial characterization of pyruvate decarboxylase
      from the yeast Hanseniaspora uvarum.
AB  - We have isolated a pyruvate decarboxylase (PDC) gene from the yeast Hanseniaspora
      uvarum using the Saccharomyces cerevisiae PDC1 gene as a probe. The nucleotide
      sequence of this gene was determined and compared to PDC genes from yeast and
      other organisms. The H. uvarum PDC gene is more than 70% identical to the S.
      cerevisiae PDC isozymes and possesses a putative thiamine diphosphate binding
      site. The PDC enzyme was purified and partially characterized. The H. uvarum PDC
      was very similar to other known PDCs; the Km for pyruvate was 0.75 mM, and the
      enzyme is a homotetramer with subunits of M(r) = 57,000.

PMID- 7725795
TI  - Development of a transformation system for the yeast Yamadazyma (Pichia) ohmeri.
AB  - This communication describes the development of genetic tools for the yeast
      Yamadazyma ohmeri. Nystatin enrichment proved highly effective for isolating
      various auxotrophic strains, which were classified by complementation analysis.
      Biosynthetic genes encoding known biochemical functions were isolated by
      polymerase chain reaction, including YoLEU2 and YoURA3 that were sequenced. Using
      these homologous genes as selective markers, DNA transformation was accomplished
      by electroporation. Transformation with pBR322-based plasmids, cut within the
      coding region of the homologous marker gene, yielded 20 to 50 stable
      transformants per microgram of DNA. In about 80% of the cases, integration of
      plasmid DNA sequence occurred by homologous recombination of a single plasmid
      into the chromosome. Excision of the plasmid permitted gene replacement, as
      illustrated by the substitution of a wild-type URA3 gene by an in vitro generated
      deletion. Sequences conferring extrachromosomal replication were isolated from Y.
      ohmeri DNA. Plasmids based on pBR322 carrying such an ARS and either selective
      markers transformed at 10(4)/microgram and were shown to replicate freely in Y.
      ohmeri at an approximate copy number of 40. Unexpectedly, we observed that BS-SKR
      derivatives carrying either YoLEU2 or YoURA3 but no Y. ohmeri ARS also replicated
      extrachromosomally. Linearization of transforming plasmids within regions
      homologous or not to chromosomal sequences stimulated transformation frequencies
      up to four-fold.

PMID- 7725794
TI  - The linkage of (1-3)-beta-glucan to chitin during cell wall assembly in
      Saccharomyces cerevisiae.
AB  - Pulse-chase experiments with [14C]glucose demonstrated that in the cell wall of
      wild-type Saccharomyces cerevisiae alkali-soluble (1-3)-beta-glucan serves as a
      precursor for alkali-insoluble (1-3)-beta-glucan. The following observations
      support the notion that the insolubilization of the glucan is caused by linkage
      to chitin: (i) degradation of chitin by chitinase completely dissolved the
      glucan, and (ii) disruption of the gene for chitin synthase 3 prevented the
      formation of alkali-insoluble glucan. These cells, unable to form a glucan-chitin
      complex, were highly vulnerable to hypo-osmotic shock indicating that the linkage
      of the two polymers significantly contributes to the mechanical strength of the
      cell wall. Conversion of alkali-soluble glucan into alkali-insoluble glucan
      occurred both early and late during budding and also in the ts-mutant cdc24-1 in
      the absence of bud formation.

PMID- 7725796
TI  - Effect of site-directed mutagenesis of conserved lysine residues upon Pas1
      protein function in peroxisome biogenesis.
AB  - The Pas1 protein (Pas1p) is required for peroxisome biogenesis in Saccharomyces
      cerevisiae and contains two putative ATP-binding sites, each within a domain
      which is conserved among members of the recently characterized AAA-family. To
      elucidate whether both putative ATP-binding sites are essential for Pas1p
      function, lysine 467 of the first and lysine 744 of the second putative ATP
      binding site were each changed to glutamate by site-directed mutagenesis. While
      replacement of lysine 744 abolished the function of the Pas1 protein in
      peroxisome biogenesis, replacement of lysine 467 had no obvious effect.

PMID- 7725797
TI  - Kluyveromyces marxianus small DNA fragments contain both autonomous replicative
      and centromeric elements that also function in Kluyveromyces lactis.
AB  - Two fragments containing both an autonomous replicating sequence (ARS) and a
      centromere have been isolated and sequenced from the yeast Kluyveromyces
      marxianus. The ARS and centromeric core sequences are only 500 bp apart, but ARS
      activity could be separated from the centromeric sequences. Centromeric sequences
      are organized in a similar way to those of budding yeasts: two well-conserved
      elements: CDEI (5' TCACGTG 3') and CDEIII (5' TNTTCCGAAAGTWAAA 3'), are separated
      by a 165 bp AT-rich (+/- 90%) CDEII element whose length is twice that of
      Saccharomyces cerevisiae CDEII but almost identical to that of K. lactis. The ARS
      core consensus sequence (5' TTTATTGTT 3') is also similar to that of K. lactis.
      Both ARS and centromeric elements function in this strain, albeit inefficiently,
      but not in S. cerevisiae. A third ARS-containing fragment with a different
      organization has been isolated and sequenced.

PMID- 7725798
TI  - Characterization of an active GST-human Cdc2 fusion protein kinase expressed in
      the fission yeast Schizosaccharomyces pombe: a new approach to the study of cell
      cycle control proteins.
AB  - Characterization of cdk (cyclin dependent kinases) substrates and studies of
      their regulation require purified enzymatic complexes of cdc2-related catalytic
      and cyclin regulatory subunits. We produced human Cdc2 kinase in the fission
      yeast Schizosaccharomyces pombe as a fusion protein with glutathione S
      transferase (GST). The GST-human Cdc2p fusion protein was active in vivo since it
      rescued a temperature-sensitive allele of cdc2. The fusion protein was purified
      using a one-step chromatography procedure with glutathione-Sepharose and
      exhibited a catalytic activity in vitro. Yeast cyclin B and suc1 were found in
      association with GST-Cdc2. A 17-fold stimulation of GST-Cdc2 kinase activity was
      obtained by incubation of recombinant human cyclin A with the S. pombe cellular
      extract prior to affinity purification. This indicates that cyclin concentration
      is limiting in this overexpression system. These findings describe a fast and
      easy production of active recombinant human Cdc2 kinase in yeast that can be used
      for biochemical studies.

PMID- 7725799
TI  - A 21.7 kb DNA segment on the left arm of yeast chromosome XIV carries WHI3, GCR2,
      SPX18, SPX19, an homologue to the heat shock gene SSB1 and 8 new open reading
      frames of unknown function.
AB  - We report the amino acid sequence of 13 open reading frames (ORF > 299 bp)
      located on a 21.7 kb DNA segment from the left arm of chromosome XIV of
      Saccharomyces cerevisiae. Five open reading frames had been entirely or partially
      sequenced previously: WHI3, GCR2, SPX19, SPX18 and a heat shock gene similar to
      SSB1. The products of 8 other ORFs are new putative proteins among which N1394 is
      probably a membrane protein. N1346 contains a leucine zipper pattern and the
      corresponding ORF presents an HAP (global regulator of respiratory genes)
      upstream activating sequence in the promoting region. N1386 shares homologies
      with the DNA structure-specific recognition protein family SSRPs and the
      corresponding ORF is preceded by an MCB (MluI cell cycle box) upstream activating
      factor.

PMID- 7725800
TI  - CAN1, a gene encoding a permease for basic amino acids in Candida albicans.
AB  - The first gene coding for an amino-acid permease of Candida albicans was
      sequenced. The DNA fragment complementing the lysine-permease deficiency was 3385
      bp long. An open reading frame of 1713 nucleotides was found encoding a protein
      of 571 amino acids, with a calculated molecular weight of 63,343. Analysis of the
      deduced primary structure revealed ten membrane spanning regions and three
      potential N-glycosylation sites. The protein sequence is strongly homologous to
      both permeases for basic amino acids (Can1 and Lyp1) of Saccharomyces cerevisiae.
      C-terminal part of another ORF (105 aa), highly homologous to the gene HAL2 of S.
      cerevisiae, was found 133 bp downstream, and in tail-to-tail orientation to the
      permease gene.

PMID- 7725801
TI  - Sequence of the PHO2-POL3 (CDC2) region of chromosome IV of Saccharomyces
      cerevisiae.
AB  - The nucleotide sequence of a 5 kb EcoRI-NcoI fragment of chromosome IV,
      contiguous to gene POL3 (CDC2), has been determined. It contains three open
      reading frames: QRI1, QRI2 and QRI7. Two of them are essential genes. QRI7 is
      homologous to the Escherichia coli orfx gene.

PMID- 7725802
TI  - Sequence analysis of a 40.2 kb DNA fragment located near the left telomere of
      yeast chromosome X.
AB  - We have sequenced on both strands a 40,257 bp fragment located near the left
      telomere of chromosome X of Saccharomyces cerevisiae. The sequenced segment
      contains 21 open reading frames (ORFs) at least 100 amino acids long. Five of the
      ORFs correspond to known amino acid sequences: two hypothetical proteins in the
      subtelomeric Y' repeat region of 65.4 and 12.8 KDa, the cytochrome B pre-mRNA
      processing CBP1 protein, the mitochondrial nuclease NUC1 and the CRT1 protein. Of
      the 16 remaining ORFs, eight show highest homologies with the S. cerevisiae
      hexose transporters family (two ORFs), the yeast alpha-glucosidase (two ORFs),
      the yeast PEP1 precursor, the Escherichia coli galactoside O-acetyltransferase,
      the S. cerevisiae 137.7 KDa protein located in the Y' region and a protein of
      unknown function of Schizosaccharomyces pombe. Finally, eight of the ORFs exhibit
      no significant similarity with any amino acid sequences described in data banks.
      DNA sequence comparison has revealed the presence of different repeated elements
      characteristic of yeast chromosome ends. Disruption studies have been performed
      on two ORFs encoding putative proteins of unknown function.

PMID- 7725803
TI  - Analysis of a 17.4 kb DNA segment of yeast chromosome II encompassing the
      ribosomal protein L19 as well as proteins with homologies to components of the
      hnRNP and snRNP complexes and to the human proliferation-associated p120 antigen.
AB  - We report the nucleotide sequence of a 17.4 kb DNA segment from the left arm of
      Saccharomyces cerevisiae chromosome II. This sequence contains 12 open reading
      frames (ORFs) longer than 300 bp and a putative autonomously replicating sequence
      (ARS). The ORF YBL0418 contains the KH motif present in several nucleic acid
      binding proteins and shares homologies with the mouse X protein of the
      heterogeneous nuclear ribonucleoprotein (hnRNP) complexes involved in pre-mRNA
      processing. YBL0424 is the yeast member of the ribosomal protein L19 (YL14)
      family. YBL0425 is related to the D1 core polypeptide of the small nuclear
      ribonucleoprotein (snRNP) particles involved in the splicing of introns. YBL0437
      is a putative homologue of the human protein p120, one of the major antigens
      associated with malignant tumours. Mcm2, a protein important for ARS activity, as
      well as Aac2, one of the three isoforms of the mitochondrial ATP/ADP carrier,
      were previously described (Yan et al., 1991; Lawson and Douglas, 1988). Four ORFs
      show no homology or particular features that could help to assess their
      functions. The last ORFs are not likely to be expressed for they are localized on
      the complementary strand of longer ORFs.

PMID- 7725804
TI  - Current awareness on yeast.

PMID- 7725805
TI  - [Pathogen-induced arthritis and autoantibody associated systemic diseases-
      diagnostic concepts in transition].

PMID- 7725806
TI  - [Value of antigen, antibody and pathogen-specific lymphocyte detection in
      diagnosis of pathogen-induced arthritis].
AB  - In the differential diagnosis of infection-related arthritis (infectious
      arthritis, viral arthritis, reactive arthritis or Reiter's syndrome, Lyme
      disease) various laboratory methods are applied for the detection of the inciting
      antigen, specific antibodies or microbe-specific T-lymphocytes. In infectious
      (septic) bacterial or fungal arthritis, the definitive diagnosis can be made only
      by recovering the organism from the synovial fluid or membrane. Also, in reactive
      arthritis following extraarticular infection with Yersinia, Salmonella, Shigella,
      Campylobacter, or Chlamydia, one of the major shifts in perception of disease
      pathogenesis has been the detection of bacterial determinants by immunological
      methods and polymerase chain reaction (PCR) actually within the joint. In
      sexually acquired reactive arthritis, the etiologic diagnosis should be based on
      the direct detection of the pathogen (mainly C. trachomatis) from the urogenital
      smear specimen. For clinical routine, serological tests for bacteria specific
      antibodies (IgM and IgA class) are often necessary to show recent or persistent
      infection with the triggering pathogen. However, a cautionary note regarding the
      diagnostic significance of antibacterial antibody profiles has been sounded in
      several studies because of the high prevalence of bacteria-specific antibodies in
      the healthy population. The same problem may arise in the interpretation of virus
      specific antibodies in the differential diagnosis of acute polyarthritis. Antigen
      specific proliferation of synovial fluid lymphocytes can confirm the clinical
      diagnosis in patients with reactive arthritis and Lyme disease, although
      unspecific proliferation to several bacteria can also be observed in reactive
      arthritis as well as in many other arthritis.

PMID- 7725808
TI  - [Antineutrophilic cytoplasmic antibodies (ANCA) in inflammatory rheumatic
      diseases: immunodiagnostic and immunopathogenetic aspects].
AB  - Anti-neutrophil cytoplasmic antibodies (ANCA) are a heterogeneous group of
      autoantibodies with a wide and diverse range of clinical associations. Over the
      past decade ANCA have been the subject of extensive investigations. In vasculitis
      the diagnostic utility of proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA
      for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA),
      respectively, is now well established. Because of their significance as tools for
      diagnosis and prognosis of "ANCA-associated vasculitides," these autoantibodies
      have been analyzed extensively as markers for underlying immunopathogenic
      disturbances. Data regarding the detection of ANCA and their diagnostic value and
      role in the pathogenesis of rheumatic disorders will be discussed in this review.
      Growing evidence points to a pathophysiologic and diagnostic relevance of the
      ANCA target antigens PR3 and MPO. To date, there is mounting evidence that ANCA
      can have pathophysiologic effects on neutrophils, and may play a direct role in
      ANCA-associated vasculitides. A pathogenic model for ANCA-mediated vasculitis
      will be presented in this paper.

PMID- 7725807
TI  - [NSAID-induced ulcers--therapy and prevention].
AB  - There is a lot of epidemiological information to calculate the risk of developing
      gastroduodenal lesions during NSAID therapy on a reliable base in an individual
      patient. In treating NSAID ulcers one has to decide whether the antirheumatic
      treatment can be stopped or whether one has to continue. In the first mentioned
      condition all antiulcer drugs can be used safely like in chronic recurrent ulcer
      disease. However, when NSAID therapy has to be continued proton pump inhibitors
      are necessary in doubled therapeutic dosage. Prophylaxis should not be made in
      all patients on NSAIDs, but is only indicated with convincing cost-benefit ratio
      in high-risk patients. Whereas H2-blockers and proton pump inhibitors seem to
      protect mainly the duodenal mucosa oral prostaglandins (Misoprostol) are
      effective in the stomach as well.

PMID- 7725809
TI  - [Diagnostic significance of scleroderma and myositis-associated autoantibodies].
AB  - In more than 95% of patients with systemic sclerosis and in about 60% of patients
      suffering from idiopathic inflammatory myopathies autoantibodies directed at
      different nuclear or cytoplasmic antigens can be detected with different methods.
      Scleroderma-associated autoantibodies can be visualized as antinuclear antibodies
      (ANA) by immunofluorescence assays using cultured monolayer cells. In case of a
      negative ANA result the diagnosis of systemic sclerosis is unlikely. In
      individual patients the different autoantibodies (against DNA topoisomerase I
      (Scl-70), centromeric antigens, fibrillarin, To (Th), RNA polymerases, NOR-90, U1
      nRNP, PM-Scl, Ku) are mutually exclusive. They can be detected early in the
      course of diseases, most often are persistent, and are closely associated with
      immunogenetic markers. They are characteristic for distinct subsets of patients
      homogeneous in clinical manifestations as well as in disease outcome. Myositis
      associated autoantibodies are directed to nuclear (about 60% of myositis
      patients; PM-Scl, Mi-2) or cytoplasmic antigens (about 35-40%; Jo-1 and other
      aminoacyl-tRNA-synthetases, signal recognition particle (SRP), KJ and others) and
      likewise are related to distinct clinical, prognostic, and immunogenetic traits
      leading to the description of characteristic antibody-based syndromes. Based on
      published results and on our own investigations, the diagnostic potential of
      scleroderma- and myositis-associated antibodies is evaluated and a new
      classification of systematic myositic and sclerodermatous disease is proposed.

PMID- 7725810
TI  - [Erythropoietin--therapeutic option in chronic polyarthritis-induced anemia].
AB  - Twenty-three patients with rheumatoid arthritis and relevant anemia (hemoglobin <
      11 g/dl) received recombinant erythropoietin (epo) in a therapy study; 90% were
      responders. A positive correlation of the total epo dose and the amelioration of
      parameters of red cell line and a negative correlation of the effect of epo and
      the systemic activity of the rheumatoid arthritis was found. The effect of the
      treatment was improved if higher serum iron and serum ferritin values were
      preexistent. Using appropriate doses of epo even patients with very active
      disease could be treated successfully. Especially in these cases epo is a
      valuable expansion of the therapeutic spectrum.

PMID- 7725811
TI  - [Chronic polyarthritis and carpal tunnel syndrome. Results of follow-up].
AB  - Between July 1974 and December 1989, carpal tunnel-syndromes (CTS) were operated
      on in 903 hands of 746 patients. 147 of these patients (191 hands) were suffering
      from chronic inflammatory joint diseases. In 11 patients CTS was the first sign
      of rheumatoid arthritis (R.A.). The hands showed intraoperatively in 44.8% (n =
      86/191) an extensive tenosynovitis with an aggressive infiltration. In 19% (n =
      36/191), we had to extend the obligate tenosynovectomy on the flexor tendon parts
      of the fingers and ligaments (28 hands). 21 articulosynovectomies on the wrist or
      finger joints were performed. In 6 hands (8.0%) tendon ruptures were repaired. A
      questionnaire was completed for 107 of 147 patients (72.8%) (with 145 operated
      hands). Clinical (77 hands) and electromyographical examinations (49 hands) were
      performed an average of 5.1 (0.7-15) years postoperatively. 20 patients (13.6%)
      died, 20 could not be traced. In 86% (n = 125/145) of the patients we achieved
      relief of pain and a marked reduction of neurological deficits. 96.3% of the
      patients were content. The improvement of function of the hand after surgical
      intervention is of a great benefit for the patient with R. A. The overall risks
      of the procedure are low (complications 14%; no recidivism). Therefore, we
      recommend surgery in early stages after a confirmed diagnosis or a reasonable
      suspicion.

PMID- 7725812
TI  - Half a century in the Pecs Anatomy Department.

PMID- 7725813
TI  - The rat dorsal vagal nucleus: features of cellular and synaptic structure.
AB  - Using the stereological, histochemical and electron microscopic approaches the
      cellular and synaptic structure of the rat dorsal vagal nucleus (DVN) were
      studied. Cellular organization of the DVN does not allow to distinguish any
      separate subnuclei but a conspicuous population of mainly small neurons in
      rostral extension of its lateral part lacking AChE activity. DVN neurons with
      high and moderate AChE activities are manifest on the 5th postnatal day. Their
      number increases on the 7th day. In this critical period of the brain sexual
      differentiation, a sexual dimorphism was observed in the activity of DVN
      cholinergic neurons. The electron microscopic studies showed a wide variety of
      the DVN synaptic patterns. In the rat DVN were found complicated synaptic
      structures resembling glomeruli. Two types of synaptic glomeruli are
      distinguished. The results suggest that DVN can be regarded as a sex-dependent
      brain area involved in a high level of information processing.

PMID- 7725814
TI  - Removal of olfactory placode prevents the development of LHRH neurons in the
      forebrain of the chick embryo: possible interaction between migrating LHRH
      neurons and highly polysialylated form of neural cell adhesion molecule (NCAM-H).
AB  - A unilateral olfactory placodectomy prevented the development of LHRH- and NCAM-H
      expressing neurons as well as NCAM-H expressing olfactory nerve on the operated
      side, whereas the development of LHRH- and NCAM-H-expressing neurons and
      olfactory nerve was not disturbed. In the embryos with an incomplete olfactory
      placodectomy, a small number of LHRH-immunoreactive (ir) cells expressing NCAM-H
      were detected in the olfactory epithelial fragments and in the NCAM-H-positive
      olfactory nerve remants which ceased to extend their axons to the forebrain. The
      lack of the central projection of the olfactory nerve caused stagnation of LHRH
      ir cells, no LHRH-ir cells being found in the forebrain. These results clearly
      suggest the importance of the structural support for the migration of LHRH-ir
      cells. Furthermore, the migrating LHRH-ir cells deviated from the poorly
      developed olfactory nerve and migrated not only to the central direction but also
      to the peripheral direction of the NCAM-H-positive medial nasal branch of the
      ophthalmic nerve of the trigeminal nerve. This suggests that the migration route
      of the LHRH neurons is not programmed in detail in the precursor cells of LHRH
      neurons in the olfactory placode. Since the migrating LHRH-ir cells were never
      independent of NCAM-H-positive neural elements in the operated embryos, it is
      suggested that not only the structural support for the migration but also the
      possible interaction between the migration of LHRH-ir cells and NCAM-H and/or
      other unknown factors may be needed for successful LHRH neuronal migration.

PMID- 7725815
TI  - Effect of various partial separations of the litters from their mother on plasma
      prolactin levels of lactating rats.
AB  - Removal of the pups results in an abrupt and marked depression in plasma
      prolactin (PRL) level of the lactating mother. The present studies were
      undertaken to investigate what kind of sensory input (smell, sound, visual, touch
      etc.) from the pups is essential for the mother to avoid the pituitary PRL
      response to pup-removal. Therefore, various partial separations were made and
      their effect on plasma PRL levels tested: a. The pups were placed into a small
      glass having holes on its cover; b. they were put into a long measuring tube not
      covered; c. the pups were placed into the feeding trough made of a wireframe; d.
      a dividing wall made of glass or metal was slowly let down when the mother
      spontaneously went away from her pups; e. the nipples were covered by a cotton
      plaster. Pituitary PRL responses were almost identical after all these
      separations and similar to that one obtained after removal of the pups from the
      cage. In addition, separation of the mother resulted in a rise in plasma
      corticosterone concentrations. The findings suggest that the pup-removal induced
      inhibition of PRL secretion is a very complex event for the mother and cannot be
      prevented by partial separations when the mother can see, smell her pups, or hear
      them or even can touch them with her nose. We assume that separation of the pups
      is a stress for the mother and cannot simply be due to the lack of just one kind
      of sensory input from the pups. This assumption is in line with our recent
      observations indicating that in lactating rat stress causes a decrease in plasma
      PRL level.

PMID- 7725816
TI  - The number of ganglion cells in the intact and regenerated nervous system in the
      earthworm (Lumbricus terrestris).
AB  - 1. The nerve cell number is higher in the cerebral ganglion than in the
      subesophageal or segmental ganglia of Lumbricus terrestris. 2. The nerve cell
      number of the subesophageal ganglion is similar to that of the segmental ganglia
      in spite that the latter developed from a fusion of several ganglia. 3. Segmental
      ganglia in front and behind the clitellum can be considered as "typical" ganglia.
      4. The most caudal segmental ganglia are less differentiated and resembles to the
      embryological state. 5. Nerve cells of the regenerating ganglia, at least in
      part, originate from undifferentiated nerve cells of the intact ganglia.

PMID- 7725817
TI  - Neurotransmitter regulation of luteinizing hormone-releasing hormone neuronal
      function.
AB  - This paper reviews some of the research which was performed in my laboratory over
      the past several years on neurotransmitter regulation of LHRH neuronal function.
      Evidence is provided that LHRH neurons are relatively unresponsiveness to
      norepinephrine in their normal resting state (plasma LH levels are low) and one
      cause of this may be due to inhibitory influences exerted by local GABA
      interneurons. Also described is evidence that concomitant with preovulatory LH
      surges and increases in hypothalamic NE secretion there also is an increase in
      tyrosine hydroxylase mRNA levels and in activity within medullary A1
      noradrenergic neurons. As well, following orchidectomy, A1 neuronal TH mRNA
      levels, hypothalamic NE secretion and plasma LH concentrations increase.
      Moreover, electrical stimuli which evoke hypothalamic NE secretion also elevate
      TH mRNA levels in A1 noradrenergic neurons. These observations indicate that
      increases in hypothalamic NE secretion are due to increases in A1 neuronal
      activity. We also examined the effects of excitatory stimuli such as NMDA and NE
      on LHRH/LH release and determined if such secretion is coupled to increases in
      LHRH mRNA. Both neurotransmitters increase LHRH mRNA levels and LH secretion.
      However, these two events are not coupled as morphine, which amplifies NE-induced
      LHRH/LH release, also blocks NE-induced increases in LHRH mRNA levels. Evidence
      is presented that this amplifying effect of morphine is due to a suppression of
      tuberinfundibular dopamine secretion thus allowing NE to evoke the release of
      LHRH from axon terminals in the median eminence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725818
TI  - Differences in hormone release patterns from the anterior pituitary and the
      pineal gland.
AB  - Patterns of hormone release from peptide- and monoamine-hormone secreting cells
      were compared. LH, GH and PRL secretion from rat anterior pituitary cells and
      melatonin secretion from the rat pineal gland fragments were studied in a
      dynamic, in vitro system. The following fundamental differences were found: 1.
      Adenohypophysial cells respond to a specific stimulus (releasing hormones) with
      hormone secretion within seconds. There is a 90-minute lag, however, between the
      beginning of specific stimulation (norepinephrine, 1 microM for 30 min) and the
      onset of melatonin (MT) release from the pineal cells. 2. Hormone secretion from
      the pituitary cells returns to the basal value five to 10 minutes after the
      stimulus has been stopped. Once initiated, MT release from the pineal lasts for
      five to seven hours even if the NE stimulus was stopped one hour before the
      beginning of the MT response. 3. A transitory increase in potassium concentration
      (by 50-100 mM) induces a sharp, distinct rise of hormone secretion from pituitary
      cells, similar in shape and size experienced as response to releasing hormone
      stimulation. Pineal cells do not respond to elevation of potassium concentration
      at all. 4. High concentration of tropic hormones can be extracted from pituitary
      cells at the end of the superfusion experiment. Their hormone content is
      equivalent to the amount released from non-stimulated cells in a 50 to 80 hours
      period (LH and GH cells). No significant quantity of MT can be extracted from non
      stimulated, disintegrated pineal cells. This diversity in the control of hormone
      secretion from anterior pituitary and the pineal gland can be considered as a
      model for peptide and monoamine-hormone producing glands.

PMID- 7725820
TI  - Estrogen in cognetive behaviors--clinical application of estrogen for dementia of
      Alzheimer type.
AB  - We may assume the presence of specific neuron elements in the region between the
      optic chiasma and the paraventricular nuclei, which are sensitive to estrogen and
      may be inhibited (or excited) by the estrogen level of the blood and in turn
      regulate (increase or decrease) the secretion of gonadotropin.

PMID- 7725819
TI  - Effects of estrogen and estrogen receptor messenger RNA levels in young and
      middle-aged female rats: comparison of medial preoptic area and mediobasal
      hypothalamus.
AB  - We examined the effects of estrogen on estrogen receptor (ER) mRNA in the rat
      hypothalamus during aging. Two-month-old (young) and 9-month-old (middle-aged)
      rats were ovariectomized (OVX) and after 10 days given an injection of estradiol
      benzoate (20 micrograms/rat). The young rats were sacrificed 4 h, 24 h and 72 h,
      and the middle-aged rats 72 h after estrogen injection. Control rats received a
      sesame oil injection. The medial preoptic area (MPO) and mediobasal hypothalamus
      (MBH) were dissected and extracted to obtain total RNAs. The levels of ER mRNA
      were evaluated by northern blotting. We found that, in the MBH, estrogen
      treatment decreased ER mRNA in young but not in middle-aged rats. In addition, ER
      mRNA levels in middle-aged OVX rats were lower than in young OVX rats. By
      contrast, estrogen failed to decrease ER mRNA in the MPO of young OVX rats. The
      ER mRNA levels in the MPO of middle-aged OVX rats were significantly higher than
      in any other groups. The present study indicates that the estrogenic regulation
      of ER mRNA is different between the MBH and the MPO, and impaired in the MBH, but
      not in the MPO of middle-aged rats.

PMID- 7725821
TI  - Reciprocal changes in prolactin and growth hormone secretion in vitro after in
      vivo estrogen treatment.
AB  - Female rats were treated in vivo with estrogen for three weeks. The pituitaries
      were then removed and their responses to somatostatin, dopamine, TRH, hGHRH(1
      44)NH2, or their combination were examined in a superfused pituitary cell system.
      Somatostatin did not decrease basal prolactin secretion in the control cells, but
      it caused a dose-dependent decrease in prolactin release from the estrogen
      pretreated cells. Estrogen pretreatment did not alter the sensitivity of
      pituitary cells to dopamine; dopamine was equally effective in the control and
      estrogen pretreated pituitaries in decreasing the basal prolactin secretion and
      TRH induced prolactin release. Prolactin release from the estrogen pretreated
      cells, stimulated by 25 nM TRH was inhibited by 1 nM somatostatin and nearly
      totally abolished by 25 nM somatostatin, whereas in the control cells only the
      higher dose of somatostatin caused some decrease in the prolactin release.
      Estrogen pretreated cells showed a reduced response to GHRH. Somatostatin did not
      decrease the basal secretion of GH in either group, but at 1 nM dose it
      completely abolished the GH release induced by equimolar concentration of GHRH.
      However, after somatostatin was eliminated from the system, a delayed GH release
      could be observed that was greater in the control pituitaries than in the
      estrogen pretreated pituitaries. It is concluded that in vivo treatment with
      estrogen reduces GH secretion in response to GHRH and increases prolactin
      secretion after TRH stimulation. After estrogen treatment, the basal and TRH
      stimulated prolactin release can be effectively reduced by somatostatin. These
      effects could be observed in vitro using estrogen free tissue culture medium for
      up to 36 hours after the removal of the pituitaries. The reciprocal changes in GH
      and prolactin secretion support the concept of the transdifferentiation of GH and
      prolactin secreting cells.

PMID- 7725822
TI  - Large clear cell adenoma of the parathyroid in a patient with MEN-1 syndrome.
      Ultrastructural study of the tumour exhibiting unusual RER formations.
AB  - A 48 year old man presented with hyperparathyroidism and acromegaly. Although
      pancreatic tumour was not demonstrated, the diagnosis of MEN-1 syndrome was made.
      The parathyroid adenoma was removed surgically and investigated by histology and
      transmission electron microscopy and was diagnosed as large clear cell adenoma
      with extensive deposition of glycogen. Much of the endoplasmic reticulum was
      present in two special forms: annulate lamellae and the rare rail-like
      configurations both of which showed continuity with the conventional RER as well
      as with each other. No obvious correlation was apparent between presence of
      special RER formations and growth rate or endocrine activity of tumour; they may
      be regarded as signs of cellular dedifferentiation.

PMID- 7725823
TI  - Diverse effects of a potent LH-RH antagonist on the LH and FSH release.
AB  - A potent LH-RH antagonist (Ac-D-Trp1,2, D-Cpa2, D-Lys6, D-Ala10 LH-RH (Antag) was
      used to study the differential regulation of FSH and LH secretion by endogenous
      LH-RH in ovariectomized (OVX) and regularly cycling rats. The endogenous LH-RH
      was suppressed by single injections of Antag in OVX animals and by long-term
      treatment with Antag in normal and OVX rats. Serum and pituitary LH and FSH, as
      well as serum estradiol (E2) and progesterone (P) was determined by RIA during
      and/or after the treatment. The direct effect of the antagonistic analog on the
      ovarian P release was tested in vitro using the isolated luteal cell system.
      Single injections of the Antag in OVX animals caused prompt and marked
      suppression of the serum LH (-80%), while no decrease of the serum FSH. Long-term
      treatment with the same analog decreased the serum LH by 50% but did not modify
      the serum FSH. In normal rats, serum LH dropped to undetectable levels, while
      serum FSH did not change significantly. Long-term treatment with the antagonist
      also resulted in divergent alterations in the pituitary gonadotropin
      concentrations. In OVX animals, the pituitary LH content moderately elevated
      (+21%), however, the FSH did not change. In normal rats, ovarian cycles were
      interrupted, and no ovulation appeared during the treatment. The pituitary LH
      concentration increased by 46%, while the FSH decreased by 43%. Marked depression
      was found in the serum P (-60%) but no significant change in the serum E2 levels.
      Incubation of isolated luteal cells with the Antag did not influence the HCG
      induced P secretion in vitro, demonstrating that the in vivo inhibitory effect of
      the antagonistic LH-RH analog on the P secretion asserts not directly on the
      ovarian LH-RH receptors, but through inhibition of the endogenous LH-RH. Our
      studies give evidence that the long-term treatment with LH-RH antagonist suppress
      the LH and P but not the FSH and E2 secretion, and provide new data suggesting
      the presence of a FSH-releasing factor in the CNS.

PMID- 7725824
TI  - Present status of knowledge about the distribution and colocalization of PACAP in
      the forebrain.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a recently
      discovered member of the secretion family. 1. PACAP is a well conserved peptide
      during the phylogenesis. It has two bioactive amidated forms: PACAP38 and PACAP27
      with 38 and 27 residues, respectively. 2. PACAP and its receptors are widely
      distributed in the central and peripheral nervous systems and in non-neural
      tissues. 3. In the central nervous system PACAP immunoreactive neuronal elements
      have been observed in the hypothalamus (magno- and parvocellular cell groups),
      both layers of the median eminence, the septum, the thalamus, the amygdaloid
      complex, the hippocampus, and various regions of the cortex. 4. In the periphery,
      PACAP was found in small sensory and parasympathetic neurons. 5. In the
      hypothalamus PACAP partially colocalizes with oxytocin- and tyrosine hydroxylase
      immunoreactivities. In the septum there is no colocalization between the two
      immunoreactivities, but PACAP- and tyrosine hydroxylase-immunoreactive fibers
      were often found to establish synaptic contacts with the same, unlabeled
      dendrite. It was reported that in the periphery, in sensory neurons PACAP
      colocalized with substance-P and in parasympathetic neurons with acetylcholin. 6.
      PACAP functions as a neurotransmitter, hypothalamic releasing factor, posterior
      pituitary hormone, and trophic factor of the nervous tissue. PACAP also
      participates in neuro-immunoendocrine mechanisms.

PMID- 7725825
TI  - Mesencephalic projections of the cochlear nucleus in the frog, Rana esculenta.
AB  - The lectin Phaseolus vulgaris leucoagglutinin was injected into chochlear nucleus
      in order to study the trajectory and projections of the auditory pathway in the
      frog. A strong contralateral and a weak ipsilateral fiber bundle representing the
      lemniscus lateralis could be followed to the torus semicircularis. The following
      areas of termination could be discerned in the mesencephalon: (1) Each of the
      five subnuclei of the torus semicircularis received fibers from the cochlear
      nucleus, the largest number of fibers terminated in the principal nucleus. (2)
      Nuclei of the mesencephalic tegmentum were supplied by fibers from the cochlear
      nucleus on both sides. (3) The nucleus isthmi was innervated by a few small
      caliber fibers, and (4) the nucleus visceralis secundarius was richly supplied by
      large caliber fibers. Two ill-defined neuron groups in the mesencephalic
      tegmentum, the nucleus reticularis isthmi (5) and (6) the nucleus profundus
      mesencaphali were conspicuously outlined by the terminals of auditory fibers.
      Their positions suggested homology to the mammalian nucleus of the lemniscus
      lateralis. (7) A few fibers and boutons were labelled in the fifth and sixth
      layers of the optic tectum. Retrogradely labelled cells were found in the nucleus
      laminaris of the torus semicircularis and in the nuclei of mesencephalic
      tegmentum. Our results indicate that the frog auditory pathway is more complex at
      the level of the secondary fiber projections than has been previously recognized.
      The retrogradely labelled neurons suggest a descending control of the cochlear
      nucleus from higher structures of the auditory pathway.

PMID- 7725826
TI  - Proctolin immunoreactive elements in the nervous system of earthworm (Lumbricus
      terrestris).
AB  - Proctolin (H-Arg-Try-Leu-Pro-Thr-OH) immunoreactive elements in the nervous
      system of earthworm (Lumbricus terrestris, L.) were detected in paraffin sections
      using peroxidase-antiperoxidase method. Each part of the central nervous system
      contains proctolin immunoreactive cell bodies. The nerve cells, according to
      their locations are motoneurons, sensory neurons as well as interneurons. A part
      of the sensory epithelial cells of the body surface are proctolin immunoreactive,
      too. The body wall muscles receive a rich proctolin immunoreactive network. It is
      supposed that proctolin acts as a neuromodulator in the nervous system of
      Lumbricus terrestris.

PMID- 7725827
TI  - Convergence of topographic projections to the inferior colliculus from the
      auditory subcollicular nuclei.
AB  - Light and electron microscope studies on experimental material were undertaken in
      order to identify the composition of sets of specific subcollicular afferents
      converging to distinct groups of neurons in the inferior colliculus and the
      morphological characteristics of their parent cells. Microinjections of the
      retrograde tracer HRP placed in gride-like distribution into the CNIC revealed
      topographical order and quantitative differences in the convergence of axon
      projections from specific regions of the VCN, DCN, MSO, LSO, VNLL and DNLL. Pilot
      studies indicated very low number of labelled neurons and without discernible
      topographic arrangement in the auditory brain-stem nuclei, when the
      microinjections were in or largely in the cortical or external nuclei of the
      inferior colliculus. Neurons occupying the ventromedial quadrant of CNIC receive
      converging contralateral input projections from the dorsal part of the DCN,
      dorsomedial half of the LSO, and DNLL as well as ipsilateral connections from the
      ventral part of the VNLL, DNLL and the dorsal half of the MSO. The set of
      converging afferents to neurons in the ventrolateral quadrant of CNIC arises from
      the contralateral part of the VCN, the DNLL and from the ipsilateral ventral part
      of the VNLL, dorsal part of the MSO and the dorsolateral half of the LSO.
      Projections to cells of the dorsomedial and dorsolateral quadrants are mirror
      images of those to the ventral ones across the transverse axis of the CNIC.

PMID- 7725828
TI  - Mapping of thyrotropin-releasing hormone (TRH) neuronal systems of rat forebrain
      projecting to the median eminence and the OVLT. Immunocytochemistry combined with
      retrograde labeling at the light and electron microscopic levels.
AB  - The thyrotropin-releasing hormone (TRH)-containing neurons that project to portal
      capillaries of the external zone of the median eminence (ME) and fenestrated
      capillaries of the organum vasculosum of the lamina terminalis (OVLT) were
      identified on thin paraffin and thick vibratome sections using a combination of
      retrograde labeling with peripherally administered Fluoro-Gold and fluorescence
      immunocytochemistry. The results indicate that the vast majority of those TRH
      neurons that project to the ME and the OVLT is located in the paraventricular
      nucleus (PVN), and most abundantly, in its medial parvicellular subdivision.
      Although numerous TRH-immunoreactive (TRH-i) neurons are present in other
      hypothalamic areas of the brain, only a few of them in the dorsal hypothalamic
      area behind the PVN and the periventricular preoptic nucleus could be
      retrogradely labeled. Since only a few Fluoro-Gold-accumulating and TRH-i
      perikarya were seen in other nuclei than the PVN, it is likely that the majority
      of nerve terminals in the OVLT also originates from TRH-i perikarya in the PVN.
      Fluoro-Gold, an electron-dense substance, is stored in the lysosomes of
      hypophysiotropic TRH-i perikarya and thus, it provides an excellent model for
      electron microscopic characterization of hypophysiotropic neurons at both the
      light and electron microscopic levels. The data together provides additional
      morphological evidence for the key role of the PVN in the regulation of TSH
      secretion.

PMID- 7725829
TI  - Schweigger-Seidel sheath or ellipsoid in the spleen of guinea hen.
AB  - Splenic Schweigger-Seidel sheath or ellipsoid was studied by anti-vimentin
      monoclonal antibodies, clones 3B4 and V9. The 3B4 mAb recognizes a cell type with
      cytoplasmic granules and long processes which make a network around the
      endothelial cells of the penicilliform capillaries. The V9 mAb identifies the
      reticular cells of the spleen which form the supporting system of the Schweigger
      Seidel sheath. The sheath covers the entire length of the penicilliform capillary
      from the central artery, including the branching area. The appearance of the
      Schweigger-Seidel sheath in a section depends on the section plane; namely, at
      the branching area its shape is highly irregular, while close to the red pulp it
      looks like a sleeve. Therefore, the English term "ellipsoid" does not cover the
      morphological appearance of this unique splenic structure; the Schweigger-Seidel
      sheath is a correct term.

PMID- 7725830
TI  - The glutamate receptor subunit GLuR1 is expressed in gonadotrophs of the anterior
      pituitary and is regulated by gonadal feedback.
AB  - An antiserum raised against a synthetic peptide corresponding to the C-terminal
      amino acid sequence (880-907) of the cloned glutamate receptor protein GluR1
      stained gonadotrophic cells in the adenohypophysis of normal male rats. The
      staining intensity was greatly increased in the hypertrophic gonadotrophs of long
      term castrated rats. These results indicate that glutamate may act directly on
      pituitary gonadotrophs as a neuroendocrine modulator. Furthermore, the expression
      of GluR1 in gonadotrophs (and thus these cells' ability to respond to glutamate)
      may be regulated by gonadal factors.

PMID- 7725831
TI  - The gonadotropin-releasing hormone (GnRH) neuron system of the clawed toad
      Xenopus laevis.
AB  - The GnRH immunoreactive (GnRH-ir) neuronal system of the Clawed toad Xenopus
      laevis was studied and compared with the GnRH-ir system of the frog Rana
      esculenta. Polyclonal antibodies against mammalian (mGnRH) and chicken type-II
      GnRH (cGnRH-II), and monoclonal antibodies against mGnRH were used in the study.
      In the Xenopus laevis, most of the immunopositive neuronal cell bodies were
      located in telencephalic (35-50 per cent) and diencephalic areas (50-65 per
      cent). About 15-20 per cent of the GnRH perikarya appeared in mesencephalic
      tegmental regions. Besides the larger GnRH fiber tracts present also in mammals,
      the toad has rich mGnRH immunopositive axon population in the mesencephalon and
      in the upper part of the medulla. A similar distribution of the GnRH-ir neuronal
      elements exists in Rana esculenta, but the number of stained cells and fibers was
      less. Specificity of the staining of cGnRH-IIir structures located in the lower
      brainstem could not be proved and therefore the study is only restricted to the
      findings with mGnRH-antibodies.

PMID- 7725832
TI  - Monoamine influence on neuropeptide gene expression during ontogenesis.
AB  - The present study aimed to check the hypothesis concerning the monoamine
      regulation of the differentiation of their target neurons during ontogenesis. For
      this aim, neuropeptide gene expression has been evaluated by in situ
      hybridization in targets for monoamines, differentiating peptidergic neurons,
      after monoamine depletion in rats during prenatal or early postnatal periods. In
      the first series of experiments, the vasopressin (VP) and oxytocin (OT) mRNA
      concentrations were measured in the supraoptic nucleus (SON) of rat fetuses at
      the 21st embryonic day (E21) following daily (E13-E20) treatment with the
      inhibitor of the catecholamine (CA) synthesis, alpha-methyl-m(p)-tyrosine.
      Similar study was performed with rats at the 11th postnatal day (P11) after daily
      (P2-P10) treatment with alpha-methyl-m-tyrosine and the neurotoxin, 6
      hydroxydopamine. In the second series of experiments, the effect of serotonin (5
      HT) depletion by the inhibitor of the 5-HT synthesis, p-chlorophenylalanine, on
      the vasoactive intestinal polypeptide (VIP) mRNA level in the suprachiasmatic
      nucleus (SCN) has been studied in fetuses and in neonates as described above. No
      changes were detected in the VP and OT mRNA concentration in the SON following CA
      depletion in fetuses, while similar treatment of neonates significantly increased
      both mRNA levels. On the contrary, the 5-HT depletion caused an increased VIP
      mRNA concentration in the SCN in fetuses but not in neonates. Thus, our data
      suggest a monoamine inhibitory influence on peptide gene expression in the
      differentiating target neurons during certain periods of ontogenesis.

PMID- 7725833
TI  - Medical experimentation and informed consent.

PMID- 7725834
TI  - Chylothorax and chylous ascites due to malignant lymphoma.
AB  - Chyle is a fluid rich in triglycerides and is characterized by the presence of
      chylomicrons. Chylous effusions are unusual complications of malignant neoplasms,
      usually lymphomas. The combination of chyloperitoneum and chylothorax is very
      rare. When abdominal lymphatics are obstructed, chylous ascites results and
      eventually leads to a chylothorax. We present the case of a 68-year-old woman
      with a chyloperitoneum and a right-sided chylothorax due to an underlying
      malignant B-cell lymphoma. After thoracocentesis and replacement therapy with
      medium chain triglycerides, she was treated with a combination of
      cyclophosphamide, vincristine and prednisone. This has resulted in a regression
      of the chylous effusions. A short review of the literature describes causes,
      diagnosis and therapy of chylous effusions.

PMID- 7725835
TI  - Sister Mary Joseph's nodule and inaugural cutaneous metastases of
      gastrointestinal adenocarcinomas.
AB  - Cutaneous metastases presenting as the first sign of cancer are rare. We present
      two cases of such metastases, one being a so-called sister Mary Joseph's nodule.
      The histologic findings revealed adenocarcinomas with features suggesting a
      primary gastrointestinal neoplasm.

PMID- 7725836
TI  - Poststreptococcal reactive arthritis: a form of acute rheumatic fever in
      adulthood.
AB  - We report the case of a middle-aged woman suffering from a relapsing sterile
      inflammatory arthritis preceded by a streptococcal infection. This observation
      suggests that streptococcal infection may need to be included in the list of
      infections known to precipitate reactive arthritis. The clinical presentation of
      poststreptococcal arthritis in adulthood and its relationship to acute rheumatic
      fever is discussed.

PMID- 7725837
TI  - Pituitary metastasis mimicking a pituitary adenoma. A description of two cases.
AB  - The cases of two elderly women treated for temporal hemianopsia due to a large
      pituitary mass with suprasellar extension are presented. In both cases, the
      clinical picture, without diabetes insipidus and cranial nerve paralysis, as well
      the neuroimaging and endocrinological investigation showing hypopituitarism, were
      suggestive of a non-secreting pituitary adenoma. In the first patient malignant
      tissue was unexpectedly encountered during transsphenoidal surgery.
      Anatomopathological investigation confirmed the presence of a metastasis of a
      breast carcinoma for which she had been treated 17 years earlier. In the second
      patient, a preoperative chest X-ray before transsphenoidal surgery revealed an
      asymptomatic bronchial tumour. Subsequently a squamous cell carcinoma with a
      metastasis in the pituitary was confirmed. These two cases illustrate the fact
      that a pituitary metastasis can closely mimic a pituitary adenoma. Even in the
      absence of suggestive symptoms such as diabetes insipidus and/or cranial nerve
      paralysis the possibility of metastatic disease in the differential diagnosis of
      a pituitary mass should always be considered.

PMID- 7725838
TI  - [Treatment of tuberculosis with a fixed combination antitubercular drug in a
      marginal population in Brussels].
AB  - Tuberculosis is a world-wide persistent problem. Treatment is usually successful
      when the bacteria are drug-susceptible and patient compliance ensured. We report
      our results of treatment of high-risk patients without social security coverage
      in Brussels. Double and triple fixed antituberculous agents in combined tablets
      were used. Cure was obtained without drug toxicity in all patients who completed
      therapy. Only 19.5% of patients failed to complete therapy.

PMID- 7725839
TI  - Towards standardization of specific protein assays.
AB  - A new international reference preparation for proteins in human serum has been
      recently proposed in Europe from the Community Bureau of Reference (Brussels)
      under the name CRM 470 (Certified Reference Material) and in the United States
      from the College of American Pathologists under the name RPPHS (Reference
      Preparation for Proteins in Human Serum). This serum based material offers the
      opportunity to the laboratories to standardize their serum protein
      concentrations, and to improve dramatically the transferability of the results
      from studies to the local working conditions. The International Federation of
      Clinical Chemistry strongly recommends the use of this preparation by all
      laboratories. The Belgian Institute of Hygiene and Epidemiology expects an
      improvement in the agreement of the results of the three proteins (IgA, IgG, CRP)
      included in its external quality control of the clinical laboratories. These
      proteins were omitted from the controls of the second semester of 1994, but would
      reappear in early 1995, after the conversion of the laboratories to the new
      protein calibrators. Of course, this implies the assignment of new reference
      ranges for most of the serum proteins, some of them being significantly modified
      (alpha 1-antitrypsin, haptoglobin, transferrin, C3, IgM). The clinical chemists
      must inform the physicians of these changes.

PMID- 7725840
TI  - Vancomycin-resistant Enterococcus faecalis: now also in Belgium.

PMID- 7725841
TI  - Glycosylation and cirrhosis.

PMID- 7725842
TI  - Epidemiology and laboratory diagnosis of hantavirus (HTV) infections.
AB  - Hantavirus (HTV) is recently discovered "hemorrhagic fever virus" belonging to
      the Bunyaviridae family, which is spread throughout the world by wild rodents
      and/or laboratory rats. During an epidemic in the Belgian-French Ardennes in
      1993, more than 200 acute cases were recorded of the milder European form of HTV
      illness, otherwise known as Nephropathia epidemica (NE). This variant may be
      recognized by the sudden onset of fever, acute renal failure, thrombocytopenia
      and sometimes by ophthalmologic complications. The symptomatology is rather
      aspecific and diagnosis can only be confirmed by serologic tests, of which the
      best option nowadays seems to be: screening by IgG EIA, followed by IgM
      confirmation with a mu-capture EIA test. Some of the tests described allow an
      evaluation of the causative serotype or even the moment of infection. Next to the
      "classic" serologic assays for detection of specific viral antibodies, we
      describe briefly our own experience with newer tests such as "high density
      particle agglutination" and "line immuno assay". Polymerase chain reaction for
      viral RNA genome typing and immunohistochemical colouring of the viral antigen in
      tissues seem to offer promising alternatives for the immediate future.

PMID- 7725844
TI  - Haemostatic abnormalities in multidrug-resistant enteric fever.
AB  - Twenty-five consecutive patients with multidrug-resistant enteric fever were
      evaluated and followed for haemostatic abnormalities. Twenty-one (84%) of the
      patients had evidence of disseminated intravascular coagulation (DIC) and 12
      (48%) also had evidence of associated fibrinolysis. Clinical bleeding was
      observed in 3 (12%) cases, and did not bear any correlation with clotting
      abnormalities. Protein C activity was found to be decreased in 11 of the 15 cases
      with DIC, and a block in its activation, as previously postulated, could not be
      substantiated. DIC was reversed in most cases within 8 days of the institution of
      specific antibiotic therapy.

PMID- 7725843
TI  - Acute myeloid leukemia and diabetes insipidus: results in 5 patients.
AB  - The clinical and hematological characteristics of 5 patients affected with both
      acute myeloid leukemia (AML) and diabetes insipidus (DI) are described. Banded
      chromosomal analysis demonstrated monosomy 7 in 2 patients and a complex
      cytogenetic rearrangement in another. No patient entered complete remission with
      standard induction chemotherapy. These data confirm that in patients with AML,
      the association of DI (with or without monosomy 7) is an unfavorable prognostic
      factor.

PMID- 7725845
TI  - Effects of calcitonin therapy on osteoporosis in patients with thalassemia.
AB  - The aim of this study was to evaluate the effects of calcitonin (CT) treatment on
      bone pain, osteoporosis, bone fractures and blood chemistry in thalassemic
      patients. Twenty-four patients with an age range of 10-24 years were included, 14
      of whom received 100 IU CT and 250 mg calcium 3 times a week. The others (n = 10)
      were followed up as a control group with only routine thalassemia therapy. After
      1 year of treatment, bone pain disappeared and radiological signs of osteoporosis
      had improved significantly (p < 0.01) in the treatment group. CT has no important
      side effects.

PMID- 7725846
TI  - Ten-year survey of incidence of infection as a cause of death in hematologic
      malignancies: study of 90 autopsied cases.
AB  - We investigated 90 autopsied cases with hematologic malignancy, including
      malignant lymphoma (ML), acute leukemia (AL), and adult T-cell leukemia (ATL)
      peculiar to our district, during the 10-year period 1982-1991 to determine the
      change in incidence of infection as a cause of death. We divided the cases into
      two groups representing the first half decade (1982-1986) and the second half
      decade (1987-1991) and compared the findings made in the two groups. Although
      infection was the major cause of death in those autopsied cases, the incidence of
      fatal infections decreased during the latter period. The incidence of fatal
      bacterial infections decreased, while fungal infections showed a relative
      increase. Pneumocystis carinii pneumonia and cytomegalovirus (CMV) infection
      occurred more frequently in patients with ATL than in those with ML or AL.
      Combined infection by more than three pathogens was observed in 2 cases of ATL.
      Our study revealed the characteristics of ATL specific to our district, and
      indicated the need to apply new strategies to prevent and treat fungal and viral
      infections in patients with hematologic malignancies.

PMID- 7725847
TI  - Autoimmune thyroid dysfunctions in hematologic malignancies treated with alpha
      interferon.
AB  - The widespread use of alpha-interferon (IFN-alpha) therapy in different diseases
      draws attention to its side effects, such as autoimmune-related diseases,
      especially thyroid autoimmune dysfunctions. Data about hepatitis and
      nonhematologic neoplasia are available, while data about hematologic malignancies
      are fragmentary. We studied the incidence of autoimmune-related disturbances and
      thyroid dysfunctions in 54 consecutive patients suffering from hematologic
      malignancies, treated with recombinant human IFN-alpha for a mean time of 15.9 +/
      8.9 months. Our results minimize the incidence of autoimmune dysfunctions in
      hematologic malignancies as side effects of IFN-alpha therapy. We registered the
      appearance of autoantibodies in only 3 females (5% of total): 2 patients (1
      affected with essential thrombocythemia and one with multiple myeloma) presented
      antithyroglobulin antibodies with no clinical symptoms; 1 patient, affected with
      essential thrombocythemia, developed antinuclear antibodies with arthralgia and
      myalgia. ARA criteria for systemic lupus erythematosus were not fulfilled but the
      therapy had to be interrupted. No patient developed thyroid dysfunction. In
      patients with hematologic malignancies, the dosage and the duration of IFN-alpha
      treatment do not seem to influence the appearance of autoantibodies, while female
      sex appears to be a risk factor.

PMID- 7725848
TI  - Congenital dyserythropoietic anemia type II associated with G6PD Seattle in a
      Sicilian child.
AB  - A 2-year-old Sicilian boy was investigated because of chronic nonspherocytic
      hemolytic anemia (CNSHA) associated with hepatosplenomegaly. Appropriate studies
      revealed deficiency of glucose-6-phosphate dehydrogenase type Seattle (G6PD
      Seattle). In addition, bone marrow morphology, serological studies and analysis
      of red cell membrane proteins revealed congenital dyserythropoietic anemia (CDA)
      type II (or HEMPAS). Because G6PD Seattle on its own does not cause CNSHA, we
      believe that the clinical manifestations in this patient are essentially due to
      the CDA type II abnormality. However, the coexistence of these two different red
      cell abnormalities may affect the clinical picture specifically by making CDA
      type II more hemolytic than it would have been otherwise.

PMID- 7725849
TI  - Observation of T cell surface antigens in the clinical course of adult T-cell
      leukemia: case report of a spontaneous remission.
AB  - A patient with acute adult T-cell leukemia (ATL) in whom spontaneous remission
      was observed without any specific treatment having been given is described. The
      abnormal cell phenotype was CD4+, CD45RO+ and CD8-. As the number of abnormal
      cells decreased, CD4+ cell count decreased and CD8+ cells and CD45RA+ cells
      increased to normal levels (45 and 77%, respectively). Further, the number of
      cells with CD45RO antigen of intermediate fluorescence intensity increased. Five
      months after admission, we assessed the patient as being in a state of complete
      clinical remission; no abnormal cells were detected in peripheral blood, lymph
      node enlargement had disappeared and the serum chemistry was normal. When the
      abnormal cells in peripheral blood had disappeared, Southern blot analysis for
      HTLV-I proviral DNA still revealed a weak monoclonal band with EcoRI digestion,
      and HTLV-I proviral DNA was detected by polymerase chain reaction analysis. Thus,
      it appeared that very few abnormal cells persisted although the laboratory
      findings for ATL were normal. Our case could contribute to the understanding of
      the mechanism that underlies spontaneous remission in ATL.

PMID- 7725850
TI  - Transient regression in lymphocyte count in B-cell chronic lymphocytic leukemia
      after viral infection.
AB  - Transient regression in the lymphocyte count of a patient with B-cell chronic
      lymphocytic leukemia (B-CLL) after viral infection is reported. A similar event
      occurred under natural interferon-alpha (IFN-alpha) treatment. It was confirmed
      that the event was not caused by a direct cytotoxic effect of IFN-alpha by
      analyzing the DNA fragmentation to estimate apoptotic and necrotic cell death
      before and after the administration of IFN-alpha. The study also suggested that
      the event was not caused by a cytostatic effect of IFN-alpha.

PMID- 7725852
TI  - Congenital dyserythropoietic anaemia type I. Report of two siblings from Saudi
      Arabia.
AB  - This study describes two siblings (a boy and a girl) affected with congenital
      dyserythropoietic anaemia type I. It is the seventh familial occurrence reported.
      The girl presented in the neonatal period with anaemia, jaundice and
      hepatosplenomegaly and required 4 blood transfusions in the first 7 months of
      life, while her brother was discovered to be anaemic and jaundiced only at the
      age of 2 years and did not receive any blood transfusion.

PMID- 7725851
TI  - L-asparaginase in acute lymphoblastic leukemia treatment: the role of human
      antithrombin III concentrates in regulating the prothrombotic state induced by
      therapy.
AB  - It is well known that L-asparaginase (L-Ase) treatment may cause thrombotic
      events in patients with acute lymphoblastic leukemia (ALL). The mechanism of this
      effect is not well understood although a reduction in plasma antithrombin III (AT
      III) levels is observed. In our study, a group of patients treated with L-Ase
      received AT III concentrates as adjuvant treatment. This adjuvant treatment
      reduced the levels of plasma D-dimer and thrombin-antithrombin complex, which are
      considered as early markers of a hypercoagulability state. These preliminary data
      suggest that large randomized trials will have to be conducted to improve our
      understanding of the role of AT III concentrates in ALL therapy.

PMID- 7725853
TI  - Isolated gingival relapse during complete hematological remission in acute
      promyelocytic leukemia.

PMID- 7725854
TI  - Immunological response to influenza virus vaccine in B-cell chronic lymphocytic
      leukaemia patients.

PMID- 7725856
TI  - [25th annual meeting of the Austrian Association of Internal Medicine.
      Abstracts].

PMID- 7725855
TI  - Utility of the Technicon H-1 flags in the detection of peripheral blood blast
      cells of paediatric acute leukaemia patients.
AB  - This study evaluates the sensitivity and positive predictive value of some of the
      morphological flags supplied by the Technicon H-1 haematological analyser to
      detect circulating blasts. A total of 1,269 venous blood samples from 91
      paediatric patients diagnosed of acute leukemia were analysed in the Technicon H
      1. A conventional microscopic manual method was used for reference. The
      prevalence was 17.7% for the presence of blasts. The results showed that all
      samples with more than 5% blasts were detected by some WBC morphological flag:
      only 5 samples (2.2%) with less than 5% blasts showed no morphological flag. In
      most cases (86%), the flags observed were either the 'Atyp' flag or the 'Blast'
      flag or both simultaneously. The positive predictive value obtained by the
      'Blast' flag for the true presence of blasts was 66.8%, and for the 'Atyp' flag
      34.9%; it was 75.8% when both flags were present simultaneously. False positives
      were associated with postchemotherapy monocytosis or severe neutropenia.

PMID- 7725857
TI  - Spinal narcotics: what should be the standard for monitoring?

PMID- 7725858
TI  - The "mark" of an educated anesthetist.

PMID- 7725860
TI  - Joint Commission anesthesia clinical indicators: an update.

PMID- 7725859
TI  - Harris v Miller.

PMID- 7725862
TI  - Analysis of House Ways and Means Health Subcommittee's healthcare reform bill.

PMID- 7725861
TI  - Third World anesthesia.
AB  - The AANA Council for Public Interest in Anesthesia has been very interested in
      the delivery of volunteer anesthesia overseas. This article was developed as part
      of the Council's volunteer anesthesia program activities, as well as in response
      to member inquiries concerning Third World anesthesia.

PMID- 7725863
TI  - The computer database for nurse anesthesia education programs.
AB  - Closures of nurse anesthesia educational programs and a resulting shortage of
      nurse anesthetists were the focus of a study by the National Commission on Nurse
      Anesthesia Education. This study occurred simultaneously with the implementation
      of an accreditation requirement for the submission of Annual Reports by the
      Council on Accreditation of Nurse Anesthesia Educational Programs (COA). Both
      groups recognized a need for routine collection of information about educational
      programs and the result was a cooperative effort between the AANA Education and
      Research Department and the COA to establish a computer database for public
      purposes. This article reviews the need for information, describes the Annual
      Report, and explains the functions and creation of the database.

PMID- 7725864
TI  - Ethical dilemmas and decisions concerning the do-not-resuscitate patient
      undergoing anesthesia.
AB  - The growing geriatric population in this country makes it increasingly difficult
      to deal with the number of do-not-resuscitate (DNR) orders. In part, this is due
      to an increase in the number of elderly undergoing anesthesia and surgery. It can
      also be attributed to a rise in complex legal, ethical, and moral issues these
      orders pose for the healthcare professional caring for the DNR patients,
      including anesthetists. The term "DNR" is confusing to many, including healthcare
      professionals. As patients progress through the perioperative period, this
      confusion is compounded by the fact that administration of anesthesia encompasses
      interventions that include intubation, ventilation, and fluid replacement. These
      interventions may be regarded as resuscitative efforts outside the operating
      room. The anesthetist must identify and sort through a maze of conflicting
      courses of action, which must match the patient's desires and personal rights.
      The topic of DNR orders is addressed as well as some of the moral and ethical
      dilemmas they pose for the Certified Registered Nurse Anesthetist (CRNA). Some
      solutions are offered to help the nurse anesthetist make those decisions that are
      most "right" for the patient.

PMID- 7725865
TI  - Atropine and ephedrine adsorption to syringe plastic.
AB  - The purpose of this study was to compare daily changes in the concentration of
      atropine or ephedrine sulfate solutions that had been stored up to 4 days in
      plastic or glass syringes. Sets of three plastic and one glass syringe were used
      for each drug; the glass syringes acted as controls. Each set of syringes was
      labeled as day 0, 1, 2, 3, or 4. Syringes with medication were laid horizontally,
      had needles attached, and were stored in the dark at an ambient temperature. Each
      day, the assigned set of syringes was analyzed by high-performance liquid
      chromatography. Results showed that the change in the ephedrine sulfate
      concentration in the plastic syringes from day 0 to day 4 was less than 1.4%.
      Atropine sulfate decreased 52% over 4 days, with the largest single drop
      occurring during the first 24 hours. It can be concluded that the two brands of
      ephedrine sulfate stored up to 4 days at ambient temperature in the brand of
      syringe used do not significantly decrease in concentration. However, this was
      not the case with the brand of atropine sulfate studied. The practice of storing
      atropine sulfate in plastic syringes should be discouraged, because of the
      possibility of loss of potency due to medication adsorption to syringe plastic.

PMID- 7725867
TI  - Spinal anesthesia with meperidine: will epinephrine prolong its duration?
AB  - Meperidine (Demerol) has local anesthetic properties separate from its opioid
      receptor agonist effect. Unlike morphine, meperidine is structurally similar to
      local anesthetics. Therefore, it is not surprising that it possesses some
      characteristics of local anesthetics. If meperidine acts like a local anesthetic,
      binding to the same receptor sites and inhibiting nerve conduction, then drugs
      that alter the action and duration of local anesthetics may have a similar effect
      on it. This double-blinded investigation used low-dose meperidine as the sole
      intrathecal agent to determine the effect of epinephrine on the duration of
      sensory blockade. Thirty male ASA physical status I through III patients between
      the ages of 58-81 years who were scheduled for transurethral resection of the
      prostate or of bladder tumors were randomly assigned to receive meperidine with
      or without epinephrine. A continuous spinal technique was utilized, and
      meperidine 0.5 mg/kg was administered after ascertaining the proper position of
      the catheter. Fourteen of the patients received epinephrine, and 16 patients did
      not. There were no statistically significant differences between the two groups
      in terms of age, height, weight, and ASA physical status. No statistically
      significant prolongation of the sensory blockade was observed with the addition
      of epinephrine. There were no statistically significant differences between the
      two groups with regard to onset time or the incidence of complications. The
      occurrence of a full motor block in the group that did not receive epinephrine
      was statistically significant.

PMID- 7725866
TI  - The effects of total intravenous anesthesia using propofol, ketamine, and
      vecuronium on cardiovascular response and wake up time.
AB  - Total intravenous anesthesia (TIVA) can be an effective alternative to
      inhalational anesthesia. Various techniques of TIVA have been associated with
      significant cardiovascular alterations and prolonged wake up times. The purpose
      of this study was to determine if TIVA utilizing propofol, ketamine, and
      vecuronium would provide stable hemodynamics in normotensive ASA physical status
      I and II patients and allow rapid awakening upon completion of surgery.
      Anesthesia was induced with propofol 1.0 mg/kg intravenously (IV), followed
      immediately by ketamine 1.0 mg/kg IV and vecuronium 0.1 mg/kg IV. Anesthesia was
      maintained by constant infusion of propofol 100-200 micrograms/kg/min and
      ketamine 17-34 micrograms/kg/min. This combination maintained hemodynamic
      stability and provided a rapid wake up time in 80% of the 40 subjects. The
      remaining 20% experienced significant tachycardia and hypertension or premature
      ventricular contractions. The mean wake up time was 9.7 minutes from time of
      neuromuscular blocking reversal to time of extubation. TIVA can be accomplished
      with propofol, ketamine, and vecuronium; however, 20% of patients experienced
      side effects, which make this method less attractive compared to alternative
      anesthetic techniques.

PMID- 7725868
TI  - Retropharyngeal dissection: a rare complication of nasotracheal intubation
      revisited--a case report.
AB  - Nasotracheal intubation is commonly performed by anesthesia practitioners.
      Knowledge of nasopharyngeal anatomy is essential to decrease the incidence of
      complications. One such complication is traumatic retropharyngeal dissection.
      Although it is rare, serious sequelae may result. A case of a retropharyngeal
      dissection without untoward sequelae is described. Recommendations and guidelines
      are presented to assist the practitioner in the event this complication is
      encountered.

PMID- 7725869
TI  - AANA journal course: update for nurse anesthetists--patient positioning.

PMID- 7725870
TI  - What is happening to the quality of research--and how can quality be measured?

PMID- 7725873
TI  - Reexpansion of atelectasis during general anaesthesia may have a prolonged
      effect.
AB  - Pulmonary atelectasis, as found during general anaesthesia, may be reexpanded by
      hyper-inflation of the lungs. The purpose of this study was to determine whether
      such a recruitment is maintained and whether this is accompanied by an improved
      gas exchange. We studied a consecutive sample of twelve lung healthy adults,
      scheduled for elective surgery. After induction of intravenous anaesthesia, the
      lungs were hyperinflated manually. The ventilationperfusion relationship (VA/Q)
      was estimated with the multiple inert gas method, and in six patients atelectasis
      was assessed by computed x-ray tomography. The mean pulmonary shunt was 7.5% of
      cardiac output after induction of anaesthesia and this decreased to 1.0% and 2.8%
      at 20 and 40 min after the recruitment manoeuvre. Perfusion of poorly ventilated
      lung regions (low VA/Q), however, increased from 3.7% to 10.6% and 7.8% at 20 and
      40 min after the recruitment, respectively. The mean alveolar-arterial oxygen
      tension difference (PA-aO2) was 14.3 kPa after induction of anaesthesia and 11.1
      kPa immediately after recruitment. Forty minutes later PA-aO2 was still 2.0 kPa
      lower than after induction of anaesthesia (95% confidence interval [CI] 0.3 to
      3.8 kPa). PA-aO2 decreased more in obese patients. The mean area of atelectasis
      decreased from 9.0 cm2 after induction of anaesthesia to 0.1 cm2 immediately
      after recruitment, and there was a slow increase to 1.9 cm2 (95% CI 0.0 to 3.9
      cm2) 40 min later. During general anaesthesia in lung healthy patients, most of
      the reexpanded atelectatic lung tissue remains inflated for at least 40 min. The
      recruitment manoeuvre decreases pulmonary shunt, but increases low VA/Q. The net
      effect on gas exchange is a small reduction of PA-aO2.

PMID- 7725872
TI  - Lactate metabolism and hypocarbic hyperventilation. An experimental study in
      piglets.
AB  - Hyperventilation has been reported to increase blood lactate levels. Uncertainty
      exists as to whether high lactate levels are caused by increased peripheral
      release or decreased hepatic uptake. Seven piglets were investigated during
      controlled normoventilation and 13 piglets during controlled hyperventilation.
      Blood was drawn from catheters in the femoral artery and vein and in the hepatic
      vein. Blood flow was measured in the femoral artery by an electromagnetic flow
      meter and in the splanchnic area by indocyanine green extraction. In addition,
      repeated muscle biopsies from the hind limb and back muscles were taken. The mean
      PaCo2 was 5.4 in the normoventilated and 3.5 kPa in the hyperventilated group.
      The average hind limb oxygen uptake was the same in both groups. The arterial
      blood lactate concentration was significantly higher (P = 0.03) in the
      hyperventilated group (2.6 mmol.l-1) as compared to the normoventilated group
      (1.5 mmol.l-1). However, the release of lactate from the hind limb, and the
      muscular content of lactate were the same in both groups. Similar and unchanged
      skeletal muscle contents of glucose-6-phosphate, fructose-1,6-diphosphate, alpha
      glycerophosphate, pyruvate, citrate and ATP were recorded in both groups. The
      splanchnic region did not take up or release lactate at normal PaCO2, but
      released lactate after 120 minutes of hyperventilation. The results indicate that
      the increased concentration of lactate during hypocarbic hyperventilation was not
      caused by an increased peripheral release from the skeletal muscles of the pig
      but could be caused by an altered splanchnic turn-over of lactate.

PMID- 7725871
TI  - Fatal myocardial depression and circulatory collapse associated with complement
      activation induced by plasma infusion in severe porcine sepsis.
AB  - We have previously reported that fresh frozen plasma (FFP) may induce a rapid
      irreversible shock when repeatedly infused in pigs challenged with Gram-negative
      sepsis. The aims of the present study were to elucidate the cardiovascular nature
      of the shock and determine the aetiologic role of tumour necrosis factor (TNF),
      complement activation and halothane anaesthesia. Three groups of anaesthetized
      piglets were inoculated with a lethal dose of live E. coli bacteria. Groups I (n
      = 8) and III (n = 8) were anaesthetized with halothane and group II (n = 8) with
      ketamine. Animals in groups I and II received repeated infusions of FFP, whereas
      animals in group III received repeated infusions of 7% albumin. Six animals in
      group I and four animals in group II died during the first plasma infusion.
      Survival time was significantly longer in group II (P = 0.04) compared to group
      I. No animals in group III died during the albumin infusions, and no adverse
      effects were observed during the infusions. In group I the plasma induced shock
      was characterized by abruptly falling mean arterial pressure, cardiac index,
      systemic vascular resistance index and left ventricular contractility.
      Concomitant increases were recorded in left ventricular filling pressure and
      central venous pressure. Group II demonstrated a similar, but delayed response.
      Plasma infusion was associated with a significant increase in terminal complement
      complex (TCC) (P < 0.03 in group I, P < 0.05 in group II) and depletion of serum
      ionized calcium. We conclude that FFP may induce fatal myocardial depression and
      circulatory collapse in severe sepsis. Complement activation may be of aetiologic
      importance.

PMID- 7725874
TI  - MEG burst suppression in an anaesthetized dog.
AB  - Recording of the magnetic fields of the brain, magnetoencephalography (MEG), has
      proved to be a valuable method in neurophysiological research. In order to study
      the feasibility of MEG recording during anaesthesia we recorded
      magnetoecephalographic burst suppression in a dog during enflurane and propofol
      anaesthesia. The observed signal distribution implies a complex current
      distribution underlying the burst activity. This experiment also proves that an
      essentially artefact-free MEG recording can be obtained during respirator
      assisted anaesthesia.

PMID- 7725875
TI  - Laryngeal mask airway guided tracheal intubation in a neonate with the Pierre
      Robin syndrome.
AB  - Endotracheal intubation in infants with the Pierre Robin syndrome may sometimes
      be impossible to accomplish by conventional means. To aid difficult tracheal
      intubation many different techniques have been described. We present a case, in
      which we successfully intubated a small-for-date newborn boy with the Pierre
      Robin syndrome by using a modified laryngeal mask airway (no. 1) as a guide for
      the endotracheal tube. The technique is easy to perform, less traumatic and less
      time-consuming than multiple attempts at laryngoscopy or blind tracheal
      intubation.

PMID- 7725877
TI  - Immediate oral hydration after epidural bupivacaine-morphine analgesia.

PMID- 7725876
TI  - Maintained unilateral analgesia.
AB  - We describe a case of a patient subjected to what proved to be an epidural
      puncture with catheter placement resulting in persistent unilateral analgesia.
      The epidurographic study by contrast medium injection through the catheter showed
      unilateral distribution of the contrast following the cranio-caudal axis in the
      anterior epidural space.

PMID- 7725878
TI  - Isoflurane anaesthesia (0.6 MAC) and hypoxic ventilatory responses in humans.
AB  - In order to evaluate the difference between poikilo-capnic (no CO2 added to
      inspired gas) and iso-capnic (CO2 added to keep end-tidal CO2 constant) hypoxic
      ventilatory responses (HVR) awake and during 0.6 MAC isoflurane anaesthesia,
      seven cardio-pulmonary healthy patients were investigated. Pneumotachography and
      capnography were used before and during hypoxia (end-tidal O2 tension approx. 7
      kPa). In the awake state, poikilo-capnic hypoxic challenges resulted in an
      increased HVR as indicated by a VE that on average increased by 1.4 +/- 1.0 (mean
      +/- s.d.) l.min-1, whereas the iso-capnic hypoxic challenges resulted in a VE
      increase that was 4.7 +/- 2.3 l.min-1 on average. In the anaesthetized state, the
      corresponding value during poikilocapnia was 1.3 +/- 0.8 l.min-1 (88% of the
      awake responses, n.s.) and during iso-capnia 2.3 +/- 1.4 l.min-1 (49% of the
      awake, P < 0.02). Awake HVR was achieved by greater tidal volumes during
      poikilocapnia as well as during isocapnic challenges, while respiratory rates
      were unchanged. In the anaesthetized state, during poikilocapnia, however, HVR
      was mediated by an increased respiratory rate, (from 17.5 +/- 1.7 breath.min-1 to
      20.2 +/- 2.2) and during isocapnia by a combination of increased rate (from 17.1
      +/- 1.9 breath.min-1 to 19.1 +/- 1.8) and tidal volume (from 496 +/- 80 to 560 +/
      83 ml). It is concluded that poikilocapnic HVR is maintained at 0.6 MAC
      isoflurane whereas iso-capnic HVR is depressed by 50%.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7725881
TI  - Fibreoptic intubation and bronchofibrescopy in anaesthesia and intensive care.

PMID- 7725879
TI  - Haemodynamic effects of thoracic epidural anaesthesia during proximal aortic
      cross-clamping in pigs.
AB  - Cross-clamping (XC) of the thoracic aorta induces a hyperdynamic circulation
      proximal to the aortic clamp. In this investigation, the effects of thoracic
      epidural anaesthesia (TEA) on the haemodynamic response to XC were studied in
      pigs. Seventeen pigs were anaesthetized with ketamine, and the thoracic aorta was
      cross-clamped for 30 minutes. In eight of the animals (TEA-group) a thoracic
      epidural block (3 ml 0.5% bupivacaine) was added to the general anaesthesia.
      Prior to XC there was a lower heart rate (HR), cardiac output (CO) and mixed
      venous oxygen saturation (SvO2) in the TEA-group compared to the nine animals
      with general anasthesia only (control-group). During XC there was an increase in
      HR, CO, SvO2 and proximal aortic blood pressure (PPROX) in both groups, without
      differences between groups. Following aortic declamping central venous pressure
      (CVP), pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure
      (PCWP) increased in both groups. Fifteen minutes after declamping, one animal in
      each group died. It was concluded that in this experimental model, TEA combined
      with general anaesthesia did not modify the haemodynamic response to XC of the
      thoracic aorta.

PMID- 7725880
TI  - Influence of halothane-diethyl-ether azeotrope and isoflurane on ventilation. Re
      evaluation of an obsolete drug.
AB  - The azeotropic mixture of halothane and diethyl-ether has been claimed to be a
      suitable anaesthetic agent for use during difficult conditions because of its
      negligible effect on circulation and ventilation. The purpose was to evaluate the
      effect of halothane-diethyl-ether azeotrope (HE) and isoflurane (ISO) on
      ventilation. 12 patients scheduled to undergo minor orthopaedic surgery and
      belonging to ASA 1, were randomly allocated to the HE group or the ISO group.
      Evaluation of resting ventilation and ventilation stimulated by hypercarbia and
      hypoxaemia was done on three occasions: (A) before anaesthesia, (B) after
      inhalational induction of anaesthesia and intubation without muscle relaxants
      when the level of anaesthesia was 1 MAC and (C) half an hour after operation and
      during recovery. Resting ventilation and the ventilatory response to hypercarbia
      during anaesthesia were maintained in the HE group but not in the ISO group,
      whereas the ventilatory response to hypoxaemia during anaesthesia was absent in
      both groups. The responses had returned to normal values in both groups during
      recovery. We conclude that halothane-diethyl-ether azeotrope is comparatively
      safe during anaesthesia with spontaneous breathing provided arterial oxygenation
      is adequate. This makes this azeotrope suitable for use by anaesthetists with
      limited experience and during difficult conditions such as civil disaster or war.

PMID- 7725882
TI  - Liver function and halothane-diethyl-ether azeotrope anaesthesia. Re-evaluation
      of an obsolete drug with special reference to early postoperative effects.
AB  - A general anaesthetic drug that fulfils requirements for use under difficult
      circumstances is the inhalation agent halothane-diethyl-ether (HE) azeotrope.
      Although both halothane and diethyl ether have been described in detail, their
      effect on the liver when given together as an azeotrope has not been
      systematically characterised. The effect on liver function was evaluated and
      compared with the effects of halothane anaesthesia (H) and spinal anaesthesia
      with tetracaine (S), the last named serving as controls. The series consisted of
      33 healthy men (ASA 1-2) receiving no medication and scheduled for inguinal
      hernia repair. The patients were randomly allocated to receive HE, H or S. The
      following parameters were estimated the day before surgery and on the first
      postoperative day: liver cell metabolism (bile acids, unconjugated bilirubin),
      cell integrity (aminotransferases), synthesizing capacity (Prothrombin complex),
      cholestasis (conjugated bilirubin, alkaline phosphatase, gamma-glutamyl
      transpeptidase), and global liver function (chenodeoxycholic load test). No major
      differences emerged between the groups. Unconjugated bilirubin was increased in
      all groups. Prothrombin complex activity was reduced in all groups. Conjugated
      bilirubin was increased in the H group. The oral bile acid load test and the
      fasting bile acid were unaltered by anaesthesia in all groups. No major impact on
      liver cell function was seen in the early post-operative period after HE
      azeotrope anaesthesia. The findings support our view that HE azeotrope could be
      considered as an alternative anaesthetic agent under field conditions.

PMID- 7725883
TI  - Failure to influence hypotension during spinal anaesthesia with a limb
      tourniquet.
AB  - Fourty patients undergoing total hip replacement under spinal anaesthesia were
      allocated randomly to have a thigh tourniquet inflated after exanguination of the
      leg not being operated on or to act as controls. Significant hypotension
      (systolic arterial pressure < 70 mm Hg) was treated with i.v. ephedrine in 6 mg
      boluses. There was no significant difference between the two groups with respect
      to systolic blood pressure or requirement of ephedrine, during the hour that the
      tourniquet was applied or the period immediately after the removal of the
      tourniquet.

PMID- 7725885
TI  - Maternal expectations and experiences of labour pain--options of 1091 Finnish
      parturients.
AB  - A prospective survey of 1091 Finnish parturients was conducted in order to
      ascertain mothers' expectations for labour pain relief, to measure the actual
      pain during all three stages of labour and to question their satisfaction and the
      adequacy of pain relief on the third day following delivery. Antenatal
      expectations for pain relief were surveyed. Mothers were questioned on pain
      levels in the delivery room and 3 days after giving birth. Pain levels were
      ascertained using a visual pain score method. Antenatally, 90% of all parturients
      anticipated a need for pain relief during labour. In the delivery room over 80%
      of all parturients described their pain as very severe to intolerable, only 4% of
      the multiparous had low pain scores (0-2). After pain treatment 50% of
      multiparous women still had pain scores from 8 to 10, which reflects a lack of
      effective pain relief. Dissatisfaction with the childbirth experience was very
      low, and was associated with instrumental deliveries, but not with the usage of
      analgesia. 51% of all parturients complained of inadequate pain relief during
      childbirth, which, in multiparous women, was significantly associated with the
      second stage of labour.

PMID- 7725884
TI  - Inhibitory effects of diclofenac on the endotoxin shock response in relation to
      endothelin turnover in the pig.
AB  - During sepsis vasoactive arachidonic acid metabolites of the cyclo-oxygenase
      pathway and the endothelium-derived vasoconstrictor endothelin-1 (ET-1) are
      released. The effects of cyclo-oxygenase pathway inhibition by diclofenac on the
      endotoxin shock response and ET-1 turnover, were investigated in five groups of
      pigs. In the first group (n = 7; controls) endotoxin (15 micrograms.kg-1.h-1
      i.v.) was infused for two hours. In a second endotoxin group (n = 7), the animals
      were pretreated with diclofenac (3 mg.kg-1 i.v.). In a third group (n = 7), high
      dose ET-1 was infused (20 pmol.kg-1.min-1 i.v.) and in a fourth group (n = 7),
      the ET-1 infusion was preceded by diclofenac. In a fifth group (n = 4), a low and
      intermediate dose of ET-1 (0.2 and 4 pmol.kg-1.min-1) was infused. A significant
      increase in ET-1-like immunoreactivity (LI) plasma levels was observed in both
      endotoxin groups, but in the diclofenac group the increase was comparatively
      delayed. Furthermore, this group showed a more stable haemodynamic course and in
      the biphasic increase of pulmonary vascular resistance seen in endotoxin
      controls, the initial peak was abolished by diclofenac. Exogenous ET-1 infusion
      indicated that not only locally released but possibly also circulating ET-1 could
      be a mediator of vascular responses to endotoxin. Indications of release from the
      lungs were seen during endotoxin infusion. Diclofenac had no effect on basal ET-1
      LI plasma levels or on the disappearance rate from plasma of ET-1-LI and the
      haemodynamic changes seen on ET-1 infusion. The inhibition of cyclo-oxygenase
      pathway by diclofenac resulted in prevention of the initial pulmonary
      hypertension and a delayed increase in plasma ET-1-LI levels in porcine endotoxin
      shock and this latter effect is not due to an increased rate of disappearance
      from plasma but rather to a decreased release of ET-1.

PMID- 7725886
TI  - Wound infiltration with ropivacaine and bupivacaine for pain after inguinal
      herniotomy.
AB  - In a double-blind, randomized study, 32 patients scheduled for elective inguinal
      herniotomy under general anaesthesia received subcutaneous infiltration with 40
      ml ropivacaine 2.5 mg/ml or bupivacaine. Postoperative pain intensity was
      assessed repeatedly for 24 hours at rest, during cough and movement on a visual
      analogue scale (VAS) and by means of pressure algometry. No differences between
      pain intensities or wound tenderness were found between the groups. The demand
      for analgesics was similar in the two groups. We conclude that incisional
      ropivacaine is as effective as bupivacaine in the management of post-herniotomy
      pain.

PMID- 7725887
TI  - Minimal influence of anaesthesia and abdominal surgery on computerized
      vectorcardiography recordings.
AB  - Myocardial infarction still represents a major cause of morbidity and mortality
      following surgical procedures. Continuous computerized on-line vector-ECG has
      previously been shown to be useful in the detection of myocardial ischaemia, in
      acute myocardial infarction and unstable angina pectoris and for ischaemia
      monitoring after PTCA procedures. This method was presently tested for the
      possible influence of anaesthesia and surgery during cholecystectomy under
      general anaesthesia (n = 9), and during inguinal hernia repairs using a spinal
      block (n = 5). The patients had no history, symptoms or signs of ischaemic heart
      disease. Analyses of vectorcardiographic changes were made in relation to
      predefined standardized anaesthetic and surgical procedures, all of which
      potentially could influence the vector-ECG. Three vectorcardiographic
      trendparameters were studied: QRS-vector difference, ST-vector magnitude and ST
      change vector magnitude. The overall vectorcardiographic changes were minimal and
      smaller than vectorcardiographic changes previously reported during myocardial
      ischaemia and infarction. Since anaesthetic and surgical procedures per se had
      only minor effects on the vector ECG recordings, it is concluded that continuous
      computerized on-line vectorcardiography will not be skewed by these procedures.
      Hence, vectorcardiography has the potential of becoming a new monitor for the
      detection of perioperative myocardial ischaemia.

PMID- 7725888
TI  - Fentanyl attenuates cardiovascular responses to tracheal extubation.
AB  - We carried out a controlled, randomized, double-blind study to examine the
      effects of intravenous fentanyl (1 or 2 micrograms kg-1) on hemodynamic changes
      during tracheal extubation and emergence from anesthesia in 60 ASA physical
      status I or II patients undergoing elective gynecological surgery. Anesthesia was
      maintained with 0.5%-1.5% isoflurane and 60% nitrous oxide (N2O) in oxygen.
      Muscle relaxation was achieved with vecuronium. The patients were randomly
      assigned to three group (each, n = 20), and fentanyl (1 or 2 micrograms kg-1), or
      saline (as a control) was given at the time of peritoneal closure. Changes in
      heart rate (HR) and blood pressure (BP) were measured during and after tracheal
      extubation. Adverse effects, including postoperative sedation and respiratory
      depression, were also assessed. The HR, systolic BP, and diastolic BP increased
      significantly during tracheal extubation in the control group (P < 0.05).
      Fentanyl 2 micrograms kg-1 attenuated the increases in these variables more
      effectively than fentanyl 1 microgram kg-1. The time interval from the study drug
      to extubation was similar in each group. Postoperative somnolence and respiratory
      depression were not observed in any patients in any of the three groups. We
      concluded that a bolus dose of intravenous fentanyl 2 micrograms kg-1 given at
      the time of peritoneal closure was of value in attenuating the cardiovascular
      changes associated with tracheal extubation and emergence from anesthesia, and
      that this treatment did not prolong the recovery. However, further studies are
      required to assess this technique in patients with cardiovascular or
      cerebrovascular diseases.

PMID- 7725889
TI  - Control of post anaesthetic shivering with nefopam hydrochloride in mildly
      hypothermic patients after neurosurgery.
AB  - Postoperative shivering may be prevented by maintaining normothermia
      intraoperatively or it may be treated using specific drugs. The aim of this study
      was to compare the efficacy of nefopam hydrochloride (nefopam) to that of
      clonidine and meperidine in patients undergoing elective neurosurgical
      procedures. Three groups of patients were included in the study. Patients in
      group A (60) received i.v., at random, 20 mg of nefopam, 50 mg of meperidine or
      150 micrograms of clonidine in the immediate postoperative period. The incidence
      of shivering and the time at which shivering ceased were noted, along with
      central temperature and main haemodynamic changes. Group B (20) received i.v., at
      random, either 10 mg of nefopam or saline before awakening from anaesthesia. The
      effects of nefopam on central temperature, oxygen consumption (Vo2), carbon
      dioxide production (VcO2), basal metabolic rate (BMR) and energy expenditure (EE)
      were investigated. Group C (10) received i.v. 20 mg of nefopam during surgery:
      cerebrospinal fluid pressure (CSFP), cerebral perfusion pressure (CPP) and
      electroencephalogram (EEG) were monitored. In group A nefopam stopped shivering
      in 95% of patients when compared to meperidine and clonidine, which were
      effective in 32% and 40% of patients respectively. In group B, only 10% of
      patients receiving nefopam had postoperative shivering, Vo2, VcO2 and EE were
      significantly lower in patients treated with nefopam than those in the control
      group. No changes in CSFP, CPP or EEG were observed in group C. In conclusion,
      nefopam seems to be more effective than clonidine or meperidine in quickly
      suppressing shivering, without producing significant adverse reactions.

PMID- 7725890
TI  - Comparison of parenteral diclofenac and ketoprofen for postoperative pain relief
      after maxillofacial surgery.
AB  - Non-steroidal anti-inflammatory drugs (NSAID) effectively reduce the need for
      opioid analgesia after various types of surgery. The efficacy of diclofenac and
      ketoprofen to relieve pain after maxillofacial surgery was compared in the
      present study. In a randomized and double-blind fashion, 90 ASA I-II patients (16
      60 yrs) were studied, divided into three groups: Thirty patients received 1.0
      mg.kg-1 diclofenac i.v. after general anaesthesia induction, before surgical
      incision, and four hours later the same dose was given i.m. Thirty patients
      received ketoprofen 1.35 mg.kg-1 i.v. and i.m., as above, and a third group of 30
      patients received a comparable volume of saline i.v. and i.m. The patients
      received supplemental analgesia using a patient controlled analgesia apparatus;
      the rescue medication consisted of 0.03 mg.kg-1 oxycodone i.v. (four-hour maximum
      dose was 0.4 mg.kg-1) during the 24-hour follow-up. The three groups were
      comparable regarding the type of maxillofacial surgery (osteotomies vs. soft
      tissue surgery). Overall, there was a lower need for i.v. oxycodone during the 24
      hour period in the diclofenac group (269 doses) than in the ketoprofen group and
      in the saline group (388 doses, each) (P < 0.01). The significantly lower number
      of oxycodone administrations in the diclofenac group was a result of a
      distinguishable difference, particularly during the first four hours after
      surgery. There was no statistically significant difference in the incidence of
      side effects of the analgesic therapy between the three groups.

PMID- 7725892
TI  - The use of non-medical/alternative treatment in multiple sclerosis. A 5 year
      follow-up study.
AB  - Forty-nine patients (22 males, 27 females) were examined and interviewed with 5
      years interval in order to determine the extent of the use of non-medical
      (alternative) treatment and whether the use influenced the natural course of
      multiple sclerosis (MS). Using clinical course, Kurtzke Disability Status scale,
      bladder and bowel function, neuropsychological tests, psychological tests,
      divorce and self-assessment score as parameters, it was found that non-medical
      treatment did not alter the course of MS. To confirm this result a clinical trial
      in a controlled design is needed. The use of non-medical treatment declined over
      the 5 years from 55% to 27%. The use of non-medical treatment could be
      interpreted as an indicator of psycho-social difficulties in MS patients.

PMID- 7725891
TI  - Central antinociceptive effects of non-steroidal anti-inflammatory drugs and
      paracetamol. Experimental studies in the rat.
AB  - BACKGROUND: These studies were undertaken to investigate the site and nature of
      the antinociceptive effect of NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) and
      paracetamol in the central nervous system (CNS). METHODS: Different nociceptive
      test models were employed: the tail-flick and hot-plate tests (thermoreceptors),
      the writhing test (visceral chemoreceptors) the "scratching, biting, licking"
      (SBL) behaviour and the colorectal distension test (mechanoreceptors). Drugs were
      given intraperitoneally (i.p.), intracerebroventricularly (i.c.v.), intrathecally
      (i.t.) or as local injection via cannulae implanted stereotactically. Nerve
      destruction was made by local injection of the neurotoxin 5,7-dihydroxytryptamine
      (5,7-DHT). Whole brain and spinal cord contents of serotonin and 5-hydroxyindole
      acetic acid (5-HIAA) were analysed by high pressure liquid chromatography (HPLC).
      RESULTS: Injections of diclofenac induced antinociception in visceral pain models
      (writhing test, colorectal distension test), but not in two models of
      somatosensory pain (tail-flick and hot-plate test). The antinociceptive effect of
      diclofenac (i.p., i.c.v., or i.t.) was reversed by i.p. naloxone. Naloxone also
      reversed the effect of diclofenac injected locally into thalamic and hypothalamic
      areas involved in pain transmission as well as in n. paragigantocellularis or n.
      raphe magnus. In addition, chemical destruction of the n. raphe region attenuated
      the antinociceptive effect of diclofenac. Inhibition of serotonergic transmission
      by pretreatment with methiothepin, ritanserin, parachlorophenylalanine (PCPA) or
      5,7-DHT also reduced the antinociceptive effect of diclofenac in a visceral pain
      model. Pretreatment with diclofenac or ibuprofen blocked pain behaviour (SBL)
      after activation of excitatory amino acid receptors of the NMDA type, but not
      pain behaviour after activation of AMPA or substance P (SP) receptors.
      Paracetamol inhibited hyperalgesia after both NMDA and SP. The antinociceptive
      effects of diclofenac, ibuprofen and paracetamol were reversed by L-arginine, but
      not by D-arginine. CONCLUSIONS: The antinociceptive effect of diclofenac involves
      a central nervous component which may be elicited from several defined areas in
      the CNS. Part of the antinociceptive effect seems to be mediated by descending
      inhibitory opioid, serotonin and/or other neurotransmitter systems interfering
      with visceral pain impulse traffic at the spinal level. NSAIDs and paracetamol
      interfere with nociception associated with spinal NMDA receptor activation. This
      effect involves an inhibitory action on spinal nitric oxide (NO) mechanisms.
      Possibly, the supraspinal antinociceptive effect of NSAIDs may be explained by an
      analogous action.

PMID- 7725893
TI  - Neurocysticercosis: a poorly understood disease.
AB  - A 22-year-old male patient of Indian origin presented with generalized seizures.
      Brain magnetic resonance imaging (MRI) showed two cystic lesions. Extensive
      screening only revealed positive skin tests for tuberculosis. Immunoassays for
      cysticerosis were negative in serum and cerebrospinal fluid. Biopsy of the
      temporal lesion revealed a cysticercus. Although neurocysticercosis is a common
      cause of seizures in patients from countries where cysticercosis is endemic, the
      diagnosis can be difficult in a patient with evidence of multiple infections or
      in whom serological evidence is lacking, as is illustrated by the present case.
      Furthermore, because the pathogenic factors determining the activity of the
      disease are poorly understood, its management represents a similar problem as it
      depends upon the activity of the disease as estimated by clinical, radiological
      and laboratory tests. The present case report illustrates these difficulties.

PMID- 7725894
TI  - Chronic colchicine-induced myopathy and neuropathy.
AB  - The presented case concerns a 77-year old man who had been chronically taking
      colchicine for treatment of gout. He was admitted because of a transient ischemic
      cerebrovascular attack with motor aphasia and complained of preexisting
      paraesthesias in the lower extremities. Neurological examination revealed a
      global muscular weakness, absent myotatic reflexes and a diminished sensation.
      Serum creatine kinase (CK) levels were increased and electromyography showed
      spontaneous fibrillations in deltoid muscles, positive spikewaves in deltoids and
      anterior tibial muscles. Motor and sensory conduction velocities were mildly
      reduced. Nerve biopsy findings were compatible with a chronic axonal neuropathy
      having produced a significant loss of myelinated axons and also denervation
      features of unmyelinated axons. In muscle, combined neurogenic and myogenic
      features were found. The former result from the axonal neuropathy. The latter
      were mainly characterized by focal myofibrillar disorganisation and accumulation
      of autophagic vacuoles in muscle fibres. The presented neuromuscular symptoms and
      signs, the increased CK values, the electromyographic and nerve conduction
      velocity findings as well as nerve and muscle biopsy observations, are consistent
      with the diagnosis of colchicine-induced myopathy and neuropathy. Furthermore,
      the disappearance of paraesthesias, normalisation of CK values, and disappearance
      of fibrillations and positive spike waves in deltoid and anterior tibial muscles
      on electromyography, after stopping of the colchicine therapy, supported the
      diagnosis.

PMID- 7725895
TI  - Cordomyelotomy in the treatment of paraplegia pain. Experience in two cases with
      long-term results.
AB  - A new operation is described for the treatment of central pain of cord origin.
      This is termed cordomyelotomy, and differs from cordectomy in that it aims at
      saving all descending neural transmission conveyed through the lateral columns.
      Three cases have been treated, two with excellent results after more than 10
      years. Cordomyelotomy is indicated in cases of paraplegia pain in which the
      paroxysmal component is predominant and the patient is both paraplegic and
      without sphincteric control.

PMID- 7725896
TI  - Distal posterior inferior cerebellar artery aneurysm association with multiple
      aneurysms.
AB  - A rare case of distal aneurysm of the posterior inferior cerebellar artery (d
      PICA) found in association with distal anterior cerebral artery (d ACA) and
      middle cerebral artery (MCA) aneurysms is described. d PICA aneurysm causing
      subarachnoid hemorrhage was successfully clipped. The aneurysmal sac was excised
      and examined pathologically; no infectious etiology was found. Aneurysms at other
      locations were not operated. The association of vascular anomalies with d PICA
      aneurysms is discussed.

PMID- 7725897
TI  - Unusual form of closed dysraphism of the cervical spine.

PMID- 7725898
TI  - Alpha-delta sleep or the continuing alpha-story.

PMID- 7725899
TI  - On the ethical acceptability of placebo application in neuropsychiatric research.

PMID- 7725900
TI  - Radial osteotomy and Sauve-Kapandji procedure for deformities of the distal
      radius.
AB  - We treated 12 patients with a posttraumatic or congenital deformity of the distal
      radius. A radial osteotomy and a Sauve-Kapandji procedure were carried out. In 9
      patients the deformity was caused by a malunited fracture; the other 3 patients
      were referred to us with a Madelung deformity. We performed 6 open wedge
      osteotomies and 6 closing wedge osteotomies. All but one patient rated the result
      of the operation as good or excellent. The reason for the only failure could be
      carpal instability.

PMID- 7725901
TI  - Utility of measurement of gentamicin release from PMMA beads in wound drainage
      fluid after in-vivo implantation.
AB  - Acute or chronic osteomyelitis in 188 patients was treated by surgical
      debridement and filling of the cavity with gentamicin-PMMA beads. The gentamicin
      concentration was measured in the total drainage fluid of the first postoperative
      day. There was no correlation between this concentration and the amount of
      implanted beads. It is impossible to predict preoperatively the gentamicin
      concentration which will be obtained in situ. The measurement of gentamicin
      concentration in the total drainage fluid of the first postoperative day and its
      comparison to the minimal bactericidal concentration of responsible pathogens,
      allow very early assessment of the effectiveness of the local antibiotherapy and
      if necessary, adaptation, of systemic antibiotherapy.

PMID- 7725902
TI  - [Long-term results of Insall's total condylar knee prosthesis (10-to-13-year
      follow-up)].
AB  - We have studied 10 to 13 years postoperatively the first 105 total knee
      arthroplasties using the Total Condylar, a semiconstrained prosthesis with
      sacrifice of the cruciate ligaments, inserted between 1979 and 1983, in 99
      patients (6 were bilateral). The average age of these patients was 73.5 years at
      the time of arthroplasty. At the time of this review, 46 patients had died (49
      prostheses) and 10 were lost to follow-up. Five knees had failed (4 infections),
      requiring prosthesis removal in three cases. The other 38 patients (41 knees)
      survived: 35 were available for detailed clinical and roentgenographic
      evaluation, 6 knees had only a clinical, x-ray, questionnaire or telephone
      evaluation. To evaluate the results of these prostheses, we used 3 different
      rating systems the SOFCOT rating system the Hospital for Special Surgery rating
      system the new scoring system of the Knee Society. The results with the HSS
      system were excellent or good in 80% of the cases. The rate of satisfactory
      results, somewhat lower than those of North American studies, is probably
      explained by the advanced age of our patients. All these prostheses were
      cemented. There was no aseptic loosening at 10 to 13 years follow-up. In
      assessing these results we can confirm the reliability of the first model of the
      Insall prosthesis, in spite of a small range of sizes, and of a rudimentary
      ancillary, which resulted in important positioning mistakes. We can confirm that
      a cemented knee prosthesis with sacrifice of the cruciate ligaments is reliable
      at more than 10 years of follow-up. The technical advancements: larger range of
      component sizes metal backed tibial plates better ancillary, which permits exact
      and reproducible placement posterially-stabilized system should yield even better
      long-term results, approaching those of total hip arthroplasty.

PMID- 7725903
TI  - Classification of bone healing after intertrochanteric osteotomies. Consequences
      for the surgical procedure and postoperative rehabilitation.
AB  - Intertrochanteric osteotomies produce a rate of 1 to 7% delayed union and
      pseudarthrosis, mainly as a result of the quality of the surgical procedure
      employed. In this retrospective and prospective study we have divided the models
      of bone healing after intertrochanteric osteotomy into 4 groups based on the
      postoperative x rays, and have taken into account only the factors of sclerosis,
      radiolucency and fragment contact in the osteotomy plane. This grouping enables
      us to evaluate the quality of the surgical procedure and to predict the
      postoperative course at an early stage, thus facilitating timely modification of
      the postoperative rehabilitation.

PMID- 7725904
TI  - Secondary effects of knee braces on the intracompartmental pressure in the
      anterior tibial compartment.
AB  - In 31 healthy volunteers aged 18 to 33 years we investigated the
      intracompartmental pressure in the anterior tibial compartment while running on a
      treadmill with, and without, a functional knee brace. All volunteers performed
      two test series with a constant running speed of 8 km/h. Prior to running, the
      pressure was documented in the supine, sitting and standing position as well as
      during running. The intracompartmental pressure in the supine position was
      significantly less without a brace compared to the pressure with a brace. This
      was also true for the sitting position and the standing position. While running
      on the treadmill the average pressure was also significantly higher with, than
      without, a brace. CLINICAL RELEVANCE: Running with a functional knee brace leads
      to increased intracompartmental pressure in the anterior tibial compartment and,
      as a consequence, may lead to a chronic compartment syndrome. Wearing a
      functional knee brace may cause secondary muscle ischemia and may be one reason
      for the increased incidence of injuries in athletes.

PMID- 7725905
TI  - [Percutaneous Herbert screw osteosynthesis of the scaphoid bone].
AB  - Scaphoid fractures are the most common carpal fractures. Conservative treatment
      is long, and non-union is frequent after immobilization in a cast. The Herbert
      procedure is an improvement, but access to the scaphoid is through an extensive
      open exposure that damages the blood vessels and the anterior radiocarpal
      ligaments. In order to solve this problem we used the Herbert screw for
      percutaneous internal fixation resulting in minimal operative trauma. This
      procedure requires intraoperative x ray guidance and the use of the accessories
      of the Herbert set except the "Jick". We operated 23 patients for acute fracture
      (19 cases) or nonunion (4 cases) of the waist of the scaphoid. In this study, the
      average follow-up was 16 months and the average age was 32 years. There were 18
      men and 5 women. In 18 cases the fracture occurred on the right side. The average
      immobilization was 15.5 days. Union was obtained in all patients. Postoperative
      range of motion was 95% of the unaffected side. Key pinch was 6% better than on
      the unaffected side (the dominant hand was affected in 81% cases). Patients
      returned to work after an average of 7 weeks.

PMID- 7725907
TI  - Traumatic release of Dupuytren's contracture.
AB  - A case of partial traumatic division of a Dupuytren's band in a 56-year-old man
      with known Dupuytren's disease is described. Management consisted of exploration
      of the wound and limited fasciectomy, with excision of the diseased fascia, the
      pretendinous band, the lateral cord and the spiral cord. Postoperative recovery
      was uneventful, and the patient returned to work. He remains well two years after
      the injury.

PMID- 7725906
TI  - The influence of radiation therapy on the Harris hip score in cementless total
      hip arthroplasty.
AB  - Heterotopic ossification may adversely influence the outcome of total hip
      arthroplasty, causing discomfort or limiting the range of motion and function of
      the hip. In this prospective study we examined the influence of prophylactic
      radiation therapy on the postoperative Harris Hip Score in cementless total hip
      arthroplasty, with a follow-up from 2 to 5 years. Radiation therapy lowered the
      incidence of unsatisfactory results and increased the Harris Hip Score in hips
      with a poor preoperative range of motion.

PMID- 7725908
TI  - Biceps tendon rupture after successful reinnervation: a case report.
AB  - Although rupture of the long head of biceps is a fairly common event, its
      etiology in young healthy individuals has been assumed to be related to an
      extraordinarily strong muscle contraction. In this report we describe such a
      rupture following minor trauma in a reinnervated muscle. The case brings up
      several points of interest concerning tendon tensile strength and potential for
      rupture.

PMID- 7725911
TI  - Scapho-capitate syndrome: distant fragment migration.
AB  - The authors wish to report a case of scapho-capitate syndrome with distant
      migration of the head of the capitate, an injury previously undescribed in
      English literature. The head of the capitate in this case, was found to lie just
      proximal to the transverse carpal ligament, deep to the median nerve which was
      tented over it. It was retrieved and replaced in its anatomical location.
      Following fixation of both fractures, satisfactory stability was restored in the
      wrist. The patient was followed for a period of nine months, at the end of which,
      his wrist was non-tender with a functional range of motion.

PMID- 7725909
TI  - Fibular pachydysostosis: an atypical case.
AB  - Pachydysostosis of the fibula is an isolated deformity of the fibula with bowing
      and lengthening. Only one report has appeared in the literature, describing four
      lesions which underwent spontaneous regression during early childhood; no therapy
      was recommended. We report a 12-year-old boy with this type of deformity, who
      developed progressive angulation and deformation of the ankle joint. An osteotomy
      was necessary to realign the fibula. One year later the patient was free of
      symptoms.

PMID- 7725913
TI  - [Granulocytic sarcoma of the larynx. Report of a case and literature review].
AB  - Granulocytic sarcoma of the larynx. Case report and review of the literature.
      Granulocytic sarcoma is a rare extramedullary tumor. It occurs either as an
      isolated tumor or associated with acute or chronic myelogenous leukemia. It has
      also been reported in patients with myelodysplastic syndromes when the
      granulocytic sarcoma is a harbinger of imminent disease progression. Granulocytic
      sarcoma can occur anywhere in the body. The larynx is a rare site of this lesion.
      A first case of glottic localisation is presented. The treatment of granulocytic
      sarcoma must include surgery, radiation and chemotherapy.

PMID- 7725910
TI  - [Treatment of post-traumatic epiphysiodesis of the radius with osteotomy of the
      2, bones of the forearm].
AB  - The authors report a case of posttraumatic closure of the distal radial
      epiphysis. Wrist pain, grip weakness and gross deformity warranted surgical
      correction of the discrepancy between radial and ulnar lengths. Simultaneous
      osteotomy of the radius and shortening of the ulna offer a less destructive
      alternative to both cosmetic and functional disorders at the wrist than the
      Kapandji-Sauve procedure.

PMID- 7725912
TI  - Degree of tumour differentiation as a prognostic factor in advanced laryngeal
      cancer.
AB  - Degree of tumour differentiation as a prognostic factor in advanced laryngeal
      cancer. As part of a retrospective analysis on treatment results in 139 patients
      with advanced laryngeal squamous cell carcinoma (T3-4) differentiation grade of
      the tumour was analyzed as a prognostic factor. Univariate analysis
      differentiation grade was related to tumour size, presence of neck node
      metastasis and conversion of N-stage during follow-up. For statistical analysis,
      patients with G1-G2 and G3-G4 were grouped. Prognosis for G3-G4 carcinomas is
      significantly worse for disease specific survival (p < 0.025), due to
      significantly more regional recurrence (p = 0.05). At multivariate analysis it
      turned out that regional control and disease specific survival in patients with
      no palpable neck nodes were adversely affected by the histological degree of
      differentiation of the diagnostic biopsy. For this group of patients extensive
      treatment of neck nodes is recommended.

PMID- 7725915
TI  - [Multi-media technique applied to surgical education].
AB  - Multimedia technique applied for surgical training: the microscopic-endoscopic
      sinus surgery. Multimedia technology is characterised by the integration of
      several communication media and by an interactive access. New or difficult
      surgical techniques are made easier and safer thanks to a new program developed
      for training microscopic-endoscopic sinus surgery.

PMID- 7725916
TI  - [Nasal valve surgery using spreader grafts. Patient demonstration].
AB  - Nasal valve surgery with spreader grafts. A case of nasal valve physiology and
      pathology is discussed. Possible surgical techniques are mentioned. The open
      approach using spreader grafts is explained. It gives an excellent view on the
      interstructural relationship between caudal end of triangular cartilage, the
      medial crus of the alar cartilage and the cartilaginous septum.

PMID- 7725917
TI  - [Endonasal ethmoidectomy in the treatment of nasal sinus polyposis].
AB  - Endonasal surgery of paranasal polyposis. Two hundred and fifty one microscopical
      sphenoethmoidectomies with a major complication rate of 2.6% are reported. Long
      term results are analysed. Nasal obstruction disappears in 96% and persists in
      70% of the cases 5 years later. Through topical steroid therapy and surgical
      experience polyp recurrence rate is reduced to 30%.

PMID- 7725914
TI  - Chondrosarcoma of the larynx. A diagnostic and therapeutic dilemma.
AB  - Chondrosarcoma of the larynx. A diagnostic and therapeutic dilemma. Chondromas
      and chondrosarcomas of the larynx are very rare. Differential diagnosis between
      benign chondromas and the different degrees of malignancy in chondrosarcomas is
      difficult. Behaviour of chondromatous tumors of the larynx differs from those of
      the overall head and neck region. A case of chondrosarcoma of the larynx is
      described. A literature review regarding chondro(sarco)mas of the larynx and the
      head and neck region is given presented.

PMID- 7725918
TI  - [Cervical complications in dental infections. Causes--diagnosis--treatment].
AB  - Head and neck complications due to dental infections. Six cases of deep neck
      infection are reported. The odontogenic origin was confirmed in five patients. In
      one case, the aetiology remained unknown. All case reports are discussed
      emphasizing cervical space anatomy, mixed microbial flora and potential
      iatrogenic treatment.

PMID- 7725919
TI  - Sleep related breathing disorders: the respiratory control system and its
      instability during sleep.
AB  - Respiratory control and instability in the breathing pattern during sleep.
      Unstable breathing during sleep plays an important role in the development of
      sleep related breathing disorders (SRBD). Periodic breathing, as a hallmark of
      this instability, is a common initiator of these disorders. In addition,
      structure and function of the upper airway are prone to intrinsic and extrinsic,
      congenital and acquired abnormalities which are as well responsible for the
      pathogenesis of SRBD.

PMID- 7725920
TI  - [Surgical treatment of iatrogenic injuries of the trachea].
AB  - Surgical treatment of iatrogenic tracheal traumata. Eight cases of tracheal
      resection with immediate anastomosis in tracheal stenosis due to prolonged
      intubation are reported. Resection-anastomosis surgery is compared to
      recalibration technique.

PMID- 7725921
TI  - Adenoid cystic carcinoma initially diagnosed and treated as hemangioma.
AB  - Adenoid cystic carcinoma initially diagnosed and treated as hemangioma. A case
      diagnosed as having a hemangioma of the soft palate according to clinical and
      arteriographic findings is discussed. Recurrence appeared one year after
      embolization. Arteriography showed no vascular lesion and histopathologic study
      revealed an adenoid cystic carcinoma. It is stated that imaging studies may be
      insufficient.

PMID- 7725923
TI  - [Guillain-Barre syndrome and hypacusia].
AB  - Guillain-Barre's Syndrome and hearing loss. A child presenting Guillain-Barre's
      syndrome, together with bilateral hearing loss is presented. The incidence of
      hypoacusis is unknown. The necessity of behavioural audiometry and
      electrophysiologic testing is stressed.

PMID- 7725922
TI  - [Swollen ear canal, not always innocent].
AB  - A swollen ear canal: not to be underestimated. The role of radiology in three
      patients with problems due to unaccomplished otitis externa is discussed. The
      choice between CT scanning and MRI in selected cases is balanced.

PMID- 7725924
TI  - Surgical management of chronic otitis media with effusion.
AB  - Surgical management of chronic otitis media with effusion. One hundred and twenty
      six children suffering from chronic otitis media with effusion (OME) were
      operated. Ninety two point eight percent had a satisfactory outcome. Surgical
      management of chronic OME is discussed.

PMID- 7725925
TI  - [Polymer-containing eye drops. II. Isotonicity and pH adjustment of polymer
      solutions].
AB  - Authors studied potentials for isotonizability and isohydria adjustment of
      viscous eye-drops. Various non-ionic, anionic, linear chain, and/or crosslinked
      polymers were applied in order to increase viscosity. They have found that
      rheological features of the solutions do not change either upon the addition of
      electrolytes or upon change in pH value. Modification in equilibrium viscosity
      values indicate the onset of dehydration. Such change occurs in concentrated
      polymer solutions only.

PMID- 7725926
TI  - In vitro biopharmaceutical investigation of antacid activity in standard
      dissolution test apparatus.
AB  - The pH stat titration and the Rossett-Rice test used especially for the reaction
      kinetical and in vitro biopharmaceutical investigation of antacids were
      standardized applying the U.S.P. Dissolution Test Apparatus with paddle stirring
      element. The developed "artificial stomach" is suitable to simulate also the
      gastric emptying. The in vitro model may give a new alternative for the in vitro
      evaluation of antacid effectiveness, because this standardized method may
      perfectly eliminate the deficiencies of the earlier test prescriptions.

PMID- 7725927
TI  - [Changes in fat metabolism in acute carbon tetrachloride intoxication of rats].
AB  - CCl4 is an organic solvent and a well known hepatotoxic agent. Injury is mediated
      by reactive free radicals, mainly-CCl3 (trichloromethyl). Liver lesion develops
      within one-two hours, however, late toxic effects may appear after a delay of
      several hours or two to three days. Some drugs and liver toxicants cause
      disturbances in synthesis and metabolism of triglycerides, cholesterol and
      lipoproteins, thus damaging the basic resource for living cells. In our
      experiments a single 1.25 ml/kg CCl4 dose was administered s.c. to male Wistar
      rats. 24 hours later triglyceride level increased in the plasma by 223%.
      Cholesterol content suffered no changes. HDL-C level decreased by 40%. LDL-C
      concentration was higher by 235%. Cholesterol/HDL-C ratio increased by 0.75% on
      account of the practically unchanged cholesterol amount in the blood. The most
      often used calculation (Friedewald equation) LDL-C/HDL-C ratio was higher by
      305%. The increased triglyceride content in the blood is in correlation with the
      fatty degeneration of the liver. The high LDL-C/HDL-C ratio may point to
      incipient atherosclerotic complications. The pathological lipid levels measured
      24 hours after intoxication claim for delayed toxic effects to be taken into
      consideration. It may be suggested to determine the main lipid parameters after
      carbon tetrachloride exposition.

PMID- 7725929
TI  - [Polymer-containing eye drops. I. Rheological characteristics of polymer
      solutions].
AB  - Authors studied rheological features of opthalmic solutions. They found that
      water soluble polymer solutions of different characteristics (non-ionic, anionic,
      linear chain, and/or cross linked) are pseudoplastic in rheological aspect.
      Rheological features exponentially increase with the concentration of the
      polymer. With the calculation of the constants of the exponential line, polymer
      concentration providing an optimum viscosity can be determined.

PMID- 7725928
TI  - [Interaction between immunomodulatory drugs in mice with special regard to
      changes of drug sensitivity and rate of bacterial translocation].
AB  - In acute toxicity experiments the changes in drug sensitivity and in the rate of
      bacterial translocation (BT) were investigated in mice treated with
      immunomodulatory drugs: dianhydrogalactitol (DAG) in doses 20 and 30 mg/kg,
      chlorpromazine (CPZ) in doses 60 and 75 mg/kg and Mannozym (M) in dose 40 mg/kg
      for zymosan content. The drugs were used separately or in combination. The
      sensitivity of mice to immunosuppressive DAG or CPZ was higher in the case of
      combined treatment, than that of separately treated ones. The rate of BT was also
      higher in combined treated mice. The pretreatment with M that has
      immunostimulatory effect, influenced neither the sensitivity of mice to DAG or
      CPZ, nor the normal very low rate of BT. The present results reinforced the
      authors' earlier observations, that the effects of immunosuppressive drugs could
      cumulate and cause more serious damage of the organism. The authors suggest that
      the increase in drug sensitivity to immunosuppressive agents is in connection
      with increased rate of BT and effect of endotoxin.

PMID- 7725930
TI  - In vitro study of cytotoxic activity of vinblastine in a free form and associated
      with nanoparticles.
AB  - The cytotoxic activities of unloaded polybutylcyanoacrylate nanoparticles (PBCN),
      free vinblastine, vinblastine-loaded nanoparticles (by incorporation and
      adsorption processes) and a mixture of vinblastine-free and unloaded PBCN were
      compared in vitro on human erythroleukemic K-562 cells. Enhanced cytotoxicity was
      observed when vinblastine was either adsorbed on PBCN or mixed with them rather
      than free. When vinblastine was incorporated into polymer matrix of
      nanoparticles, a lag period and postponed cytotoxic effect on K-562 cells were
      observed.

PMID- 7725931
TI  - Professor Dr. Friedrich Loew, 37 years editor-in-chief of Acta Neurochirurgica.

PMID- 7725933
TI  - Removal of aneurysmal bone cyst in the area of C1, C2 and foramen magnum. Follow
      up of surgical osteoplastic repair by means of 3 D CT studies 15 years later.
AB  - First, the author relates his memories of his first encounter with the new Editor
      in-Chief of the Acta Neurochirurgica in 1957 and the reasons why it made such an
      unforgettable impression. Next, follows a discussion of the technical
      difficulties in the treatment of spinal aneurysmal bone cysts, which may produce
      extensive destruction of its bony elements. The relatively rare occurrence of
      these lesions and resulting limited experience provide insufficient grounds for
      developing rigid rules of surgical treatment. Their treatment must rather rely on
      experience by means of examples (paradigms). The present author's principles of
      surgical strategy are total removal of these cysts and repair by means of
      stabilizing bony autotransplants. A description is given of an unusual case of an
      aneurysmal bone cyst localized in the cervical-occipital transition area in which
      3 D CT images give a better view on stabilization reached by osteoplastic repair
      of the destroyed structures than can be achieved with previous imaging methods.

PMID- 7725932
TI  - Resection surgery for partial epilepsy. Relation of surgical outcome with some
      aspects of the epileptogenic process and surgical approach.
AB  - In spite of the progressive improvement of the results of resective surgery for
      epilepsy, the number of not significantly benefited patients remains high. An
      attempt was made to find out a relation between outcome and some aspects of the
      pathophysiological organization of the epileptogenic process and of the surgical
      procedure. Chi-square and logistic regression statistic analyses were utilized.
      The study was retrospectively performed on 138 surgically treated patients having
      a minimum follow-up of three years. Three classes of surgical outcome were
      considered: completely seizure free (including aura; 86 cases, 62.3%),
      significant seizure reduction (31 cases, 22.5%), and no significant improvement
      (21 cases, 15.2%). What follows was brought into evidence by the study. 1) On the
      diagnostic side, the spatial arrangement (focal, unilateral, multifocal) of both
      the interictal and the ictal epileptic electrocerebral activities are
      significantly associated with the surgical outcome. Their relative impact on
      outcome is related to the presence of a structural lesion: when a lesion is
      documented, the interictal activity has the higher value: vice versa, when no
      lesion is apparent, the role of the ictal activity is prevalent. However, the
      presence, as well as the nature of the lesion, per se, are not significantly
      associated with outcome. 2) On the surgical side, the extent of resection of both
      the structural lesion and of the epileptogenic zone are highly associated with
      the surgical result; the extent of lesion resection prevails on that of the
      epileptogenic zone. The type of surgical approach (hemispherectomy: 17 cases;
      temporal lobectomy: 67 cases; extratemporal resection: 54 cases) has no
      significant relation to the outcome. The value and the limits of the results
      obtained are discussed.

PMID- 7725934
TI  - Cause, distribution and significance of episodes of reduced cerebral perfusion
      pressure following head injury.
AB  - A group of 74 patients with head injury (54 severe, 17 moderate and 3 minor) had
      continuous monitoring of both arterial and intracranial pressure with computer
      based registration of these pressures, cerebral perfusion pressure and other
      variables. In 60 patients cerebral perfusion pressure CPP fell below 60 mm Hg for
      periods of 5 minutes or longer. The distribution over time of these reductions in
      CPP during up to 12 days of monitoring was studied, and each episode of reduced
      CPP was attributed to a fall in arterial pressure, an increase in intracranial
      pressure, or both. Two clusters of reduced CPP were found, one during the first
      24 hours of monitoring, when reduced CPP was mainly caused by a reduction in
      arterial pressure, and the other at 5 or 6 days after injury, when reduced CPP
      was due mainly to an increase in intracranial pressure. There was a significant
      correlation between low CPP due to reduced arterial pressure and the Injury
      Severity Score (p < 0.001), suggesting that resuscitative measures may have been
      less than optimal in these cases. There was also significant correlation between
      the duration of low CPP and low arterial pressure and an adverse outcome from
      injury as assessed at 6, 12 and 24 months after injury (p < 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7725935
TI  - Indication, technique and results of facial nerve reconstruction.
AB  - 160 patients with various intra- or extracranial pathologies were treated by
      microsurgical facial nerve reconstruction at Nordstadt Neurosurgical Clinic
      between 1978 and 1993. Facial nerve reconstruction was accomplished along the
      anatomical course of the facial nerve from its origin at the brainstem, within
      the mastoid, at the stylomastoid foramen and within the face. Mostly,
      reconstruction was indicated because of nerve discontinuity (n = 61), whereas
      facial nerve reanimation with a donor nerve such as the contralateral facial
      nerve or the ipsilateral hypoglossal nerve was indicated in 99 cases of loss of a
      proximal nerve stump. Depending on the site of the lesion reinnervation started
      at 5 to 15 months postoperatively lasting for 2 to 3 years with overall
      satisfactory results. 69% of all the patients regained good symmetry on rest,
      complete eye closure equivalent to House-Brackmann-Score III: Patients with
      complete failures either suffered of non-related diseases such as cancer leading
      to death before the estimated time of recovery or were exposed to radiation or
      received facial nerve reconstruction after long-standing facial deficit and
      marked muscular atrophy. The indication of the adequate method depends on the
      clinical course with or without preexisting facial paresis, on considering the
      intraoperative state of the facial nerve, the identification and microsurgical
      preparation of adequate nerve stumps, as well as on the adaptation techniques and
      the postoperative guidance of the patient. We conclude that facial nerve
      reconstruction by transplantation at either site of the nerve course or by
      reanimation with a donor nerve are effective and reliable procedures of treatment
      leading to satisfactory functional and cosmetic results.

PMID- 7725936
TI  - The temporo-polar approach to basilar artery aneurysms with or without zygomatic
      arch translocation.
AB  - Since the publication of the temporo-polar approach to basilar artery aneurysms
      by Sano (1980 and 1987), various modifications of the approach were reported. The
      approach provides a better view and a wider operating field than the subtemporal
      or pterional ones. Usually the approach does not need temporary remove of the
      zygomatic arch. If however, a basilar tip aneurysm is located very high above the
      posterior clinoid, temporary removal of the zygomatic arch is necessary which is
      sutured back to its original position at the end of the operation.

PMID- 7725937
TI  - The invasiveness in vitro of brain tumour derived-cells depends on their micro
      eco system.
AB  - In order to investigate the invasiveness of brain tumours, fragments of freshly
      resected tumours are transferred into cell culture vessels to form monolayers.
      The tumour derived monolayer cells are tested in two different in vitro assays
      for invasiveness: the collagen type I gel and the embryonic chick heart. Nine of
      the 10 tumour derived cells infiltrated into the collagen gel, independently of
      their clinical malignancy. Only 4 of the 10 tumour derived cells invaded the
      embryonic chick heart. Invasion into chick heart in vitro correlated with
      malignancy in vivo. The results speak for the hypothesis that the micro
      environment of the embryonic chick heart allows expression of the invasive
      character of the brain tumour cells, while the collagen type I in contrast
      indicates only cell motility.

PMID- 7725938
TI  - Hypophyseal ligaments.
AB  - Described are for the first time: a. Posterolateral hypophyseal ligament which is
      seen in most dissections b. Anterolateral ligament which is always developed c. A
      middle superior ligament d. Inferior anterior and e. inferior posterior
      hypophyseal ligament.

PMID- 7725940
TI  - Fourteen years to achieve the laying of the foundation of the European
      Association of Neurosurgical Societies (EANS): Brussels (1957)--Madrid (1967)-
      Prague (1971).

PMID- 7725939
TI  - Stereotactic microresection of small cerebral vascular malformations (SCVM).
AB  - Between 1988-1993 we performed CT-stereotactic guided microsurgical resection as
      a one-session-procedure in 46 patients bearing small (< 30 mm) cerebral vascular
      malformations (SCVM). The location of the SCVM was deep subcortical in 38
      patients, temporal medio- basal in 3 and brainstem in 5. The surgical technique
      intended to minimise invasiveness by reducing the operative approach to a size
      less than the diameter of the lesion concerned. The mean diameter of our SCVM's
      was 20 mm ranging from 10 to 30 mm. Histologically we found 23 arteriovenous
      malformations, 22 cavernous malformations and 1 capillary telangiectasia
      (capillary malformation). Clinical symptomatology consisted mainly of seizures,
      (progressive) neurological deficit and (minute) acute intracerebral bleeding. The
      SCVMs could be demonstrated by contrast-enhanced CT as well as by MRI. 15 of the
      AVM's revealed as angiographically occult. Complete microsurgical resection of
      the SCVM was accomplished in all cases with a surgical morbidity of 6.5% and no
      operative mortality. In 14 patients, most of them with initial acute
      intracerebral haemorrhage, the pronounced focal neurological deficit improved.
      During the follow-up period (1/2-5 years) no rebleeding occurred. As far as
      epileptic seizures were concerned 13 patients became seizure-free without
      anticonvulsants and 11 patients seizure-free with anticonvulsant, in the
      remaining 4 patients seizures were reduced in frequency.

PMID- 7725941
TI  - Cavernous malformations of the brain stem. A review of 139 cases.
AB  - A retrospective analysis of 139 patients with brain stem cavernous malformations
      is presented. The material consists of 41 cases from Bern and Phoenix and 98
      further well-documented cases from the literature. Sixty-eight patients were
      male, 70 were female. The average age was 31.8 + 11.8 years. Sixty-two percent of
      the cavernous malformations were in the pons, 14% were in the mesencephalon, 12%
      were in the pontomesencephalic and in the pontomedullary junction, and 5% were in
      the medulla. Eighty-eight percent of the patients showed evidence of recent or
      previous hemorrhage, 55% had one hemorrhage. 17% had two hemorrhages, and 17% had
      three or more hemorrhages. Twelve patients died from a hemorrhage, 5 with the
      first bleeding and 7 with a rebleeding. The minimum bleeding rate was 2.7% per
      year and the average rebleeding rate 21% per year and per lesion. Most lesions
      had a diameter between 10 and 30 mm. Increase in size was observed in 12 of the
      patients; this corresponds to about 21% when only patients with a follow-up of at
      least one year are considered. In 93 patients the cavernous malformation was
      removed operatively while in 30 patients the lesion was not removed. In the group
      with conservative management at the end of the observation period (up to 25 and
      32 years), 66.6% had no or only a slight neurological deficit, 6.7% were
      moderately disabled, 6.7% were completely dependent, and 20% had died. In the
      group treated surgically 83.9% had no or only a slight neurological deficit, and
      15% were moderately disabled. One patient remained severely disabled, no patient
      died. The limitations of the retrospective nature of this study are stressed.

PMID- 7725942
TI  - Sellar and parasellar extra-axial cavernous hemangiomas.
AB  - Cavernous hemangiomas can grow extra-axially within dural sinuses, particularly
      the cavernous sinus and present like tumours. Five cases of cavernous hemangiomas
      arising within or from the wall of the cavernous sinus are reported. Three of
      them had an "endophytic" growth within the cavernous sinus with a lateral
      extension into the middle cranial fossa, a medial extension into the sella and an
      anterior extension into the superior orbital fissure. Two cases presented with an
      "exophytic" extension from the sinus wall at the point of entry of the third and
      fourth cranial nerves respectively. These patterns of growths are best
      appreciated by MRI. Keeping in mind that these lesions are contained within a
      pseudocapsule will help in planing surgical strategy. Characteristic MRI findings
      of cavernous hemangiomas in this location include hypo-intensity on T 1-weighted
      images, marked hyperintensity on T2-weighted images and Gadolinium enhancement.

PMID- 7725944
TI  - Glomus jugulare tumours: a review of 61 cases.
AB  - A retrospective study of 61 patients with glomus jugulare tumours treated at the
      National Hospital for Neurology and Neurosurgery, and at the Royal National
      Throat, Nose and Ear Hospital, London. The average age at presentation was 41.7
      years. The patients were mainly treated by a posterolateral combined
      otoneurosurgical approach. 42/61 of the patients had total or subtotal excision
      of their tumours, 7/61 had partial removal and the remaining 11/61 had no
      operation. Only one case required a 2-staged procedure. There were two deaths in
      the postoperative period, one from intracerebral haemorrhage and the other from
      the left hemisphere infarction. Postoperative radiotherapy was given to 5/7 of
      the patients who had partial removal. 3/40 of the patients with total removal had
      postoperative radiotherapy, and a further 3/40 had received radiotherapy pre
      operatively. Of the 11 patients who did not undergo surgery, 7/11 were treated
      with radiotherapy and 4/11 had embolisation only.

PMID- 7725943
TI  - Frontotemporal epidural approach to trigeminal neurinomas.
AB  - From 1980 through 1993 a series of 44 patients with trigeminal neurinomas was
      treated. Five of them were operated on for the remainder of the tumour as they
      had undergone previous surgery elsewhere, 35 were operated on for the first time,
      and 4 were not operated on for various reasons. An epidural approach to the
      neurinomas originating in the branches of the Vth nerve peripherally to the
      Gasserian ganglion (GG) was used. In the neurinomas originating in the GG or in
      the root of the Vth nerve, either an epidural-transdural approach or an epidural
      transdural-transpetrous approach was used. All tumours operated on using the
      approach described in this article were completely removed. In 10 patients, the
      Vth nerve sensory deficits increased in comparison with preoperative deficits; in
      9 their state remained unaltered; and in 11 the sensory function of the Vth nerve
      improved. In those patients who had experienced pre-operative atypical trigeminal
      pain, the pain disappeared after surgery. There was no additional treatment:
      radiosurgery, irradiation or chemotherapy. Histopathological examination did not
      reveal any malignant changes in the tumours in any of the patients. Based on our
      own experience and on the published data it is believed that the best treatment
      for trigeminal neurinomas is complete microsurgical removal of the lesion.

PMID- 7725946
TI  - Images and icons.
AB  - Modern images have became essential to our daily work because they provide high
      quality representations which, with admittedly some difficulties and pitfalls,
      allow detection and diagnosis of lesions and moreover inspire and guide every
      step of surgery. This place and value of the image as the main source of
      technical information required for the patient's management is straightforward
      and raises no major epistemological problem. However our use of images easily
      escapes critical thinking. Images may impose their own power and rationality.
      Medical images are powerful for the patient and for the doctor because they
      contain an unlimited source of explanation for the disease, they make disease and
      functional complaints, comprehensible. They are important for the surgeons
      because they offer an unique and irreplaceable guide to the lesions, they make it
      visible, they give shape and in fact reality to what in the patient, belongs to
      surgery. This power of medical images is irrefutable because, rather than mere
      representations, they are analogical reflexions of the real body with its real
      lesions, there is an ontological continuity between image and reality. For these
      and some other reasons we are tempted to give to images a consideration which
      should be due only to the patient himself. This temptation is idolatrous in
      nature. Under a number of different aspects this temptation pervades the entire
      field of medicine and might ultimately narrow our vision of patients, our vision
      of man.

PMID- 7725945
TI  - Surgery of giant gliomas of chiasma and IIIrd ventricle.
AB  - During a period of 17 years (from 1976 till now) 45 patients with giant gliomas
      of the chiasma and the IIIrd ventricle out of a total amount of 120 patients with
      hypothalamic gliomas were operated. The following classification of tumours was
      used: I) tumours with predominant anterior growth; II) tumours which infiltrate
      chiasma and penetrate into the IIIrd ventricle; III) gliomas of the floor of the
      IIIrd ventricle and the chiasma, growing into the ventricle cavity; IV) tumours
      of the chiasma, optic tract and thalamus. The authors come to the conclusion,
      that surgical removal of giant tumours of the chiasma and the IIIrd ventricle,
      though risk, may result in an improvement or stabilisation of visual functions
      (77%) and a long period free from recurrencies (9.5%). The postoperative period
      is relatively favourable and the mortality is low (6%). The main contraindication
      in our opinion is a wide infiltration of adjacent brain structures by the tumour
      and spreading along both optical tracts. We consider the giant size of a tumour
      in itself a sufficient indication for surgery.

PMID- 7725948
TI  - Role of pia mater vascularization of the tumour in the surgical outcome of
      intracranial meningiomas.
AB  - The authors reviewed a personal series of 150 consecutive cases of intracranial
      meningiomas operated on between 1974 and 1988 with the aim of finding out the
      main prognostic factors determining surgical outcome. Severity of pre-operative
      clinical status and size of the tumour were found to be significant adverse
      factors, p < 0.001 and p < 0.01, respectively. In this article the authors stress
      on the role played in prognosis by pia mater vascularization of the tumour. When
      the tumour vascular supply predominated from pial-cortical arteries, in most
      cases cleavage could not be found in the arachnoid plane, but only in the subpial
      plane (because of incorporation of pia mater into the tumour "capsule"). Clinical
      consequences were that in the most eloquent areas (for example in the central
      region) a bad outcome--with transient or permanent deficit--frequently occurred
      when cleaving could not be performed in the arachnoid plane (p < 0.001). The
      neurological disorders were due to cortical and underlying sub-cortical ischaemia
      and haemorrhagic infarction. Participation of the pia mater in the tumour
      vascular supply can be predicted pre-operatively, directly on selective
      internal/external carotid angiograms, indirectly by the presence of an important
      peritumoural hypodensity on CT scan (which--according to our findings--is an
      indication of predominant pial-cortical vascular supply to the tumour). The
      positive correlation between cortical-pial supply (and its consequences) and
      tumour size (p < 0.001), pleads for surgery of meningioma at the earliest
      possible stage provided there are no contra-indications.

PMID- 7725950
TI  - Dietary fat and breast cancer: controversy and biological plausibility.

PMID- 7725949
TI  - Cranio-cervical decompression for Chiari I malformation. A retrospective
      evaluation of functional outcome with particular attention to the motor deficits.
AB  - We report a series of 26 patients affected by a Chiari I malformation treated at
      our department between 1987 and 1993. All patients underwent pre- and
      postoperative evaluation by magnetic resonance imaging (MRI). Sequential
      perioperative motor evoked potential (MEP) recordings were performed in 8
      patients. The preoperative symptoms can be divided into four subgroups:
      cephalgias (84.6%), cranial nerve deficits (69.2%), motor deficits (76.9%),
      sensory deficits (73%). Twenty-five out of 26 patients underwent craniovertebral
      decompression, 1 a transoral anterior decompression. One patient died 2 months
      after surgery because of progressive pulmonary failure. We registered following
      postoperative complications transient hypoglossal palsy (1 case), vertigo (2
      cases), meningitis (1 case), minor CSF leaks (3 cases). Cephalgias subsided in 17
      and improved in 4 out of 22 patients. Cranial nerve deficits improved in 8 and
      were stabilized in 7 out of 18 patients. A limited recovery of trigeminal
      function was possibly due to nuclear lesions. Five patients whose vestibular
      disturbances were not relieved by surgery were put on a course of carbazepine.
      Vertigo resolved in one case and in two others improved. While hypesthesia
      improved after decompression, the other sensory deficits were stabilized in 5% of
      the patients. Spasticity improved in 12 out of 18 patients, but weakness only in
      7 out of 17 patients. Motor disturbances were always detected by MEP-recording.
      MEP-characteristics were not specific, resembling those of patients with other
      intra-, extramedullary myelopathies. Functional recovery was not matched by an
      improvement of the MEP parameters. MEP may be used as tool for surveillance of
      patients whose clinical findings are not progressive and are not at first
      surgical candidates.

PMID- 7725947
TI  - Interstitial 125-iodine radiosurgery of low-grade gliomas of the insula of Reil.
AB  - Between 1979 and 1991 67 patients with low-grade gliomas of the insula (of Reil)
      were treated with 125-iodine interstitial radiosurgery. Retrospective analysis
      with a median follow-up of 55 months demonstrated a 5- and 10-year survival rate
      of 54% and 47%, respectively, for all low-grade gliomas treated and a 5- and 10
      year survival rate of 57% for 49 patients with astrocytomas WHO grade II analysed
      separately. The median Karnofsky performance status of survivors was 90%.
      Malignant change was the cause of death in 85%, failure to control tumour growth
      in the remaining cases. Multivariate analysis with a Cox proportional hazard
      model identified solely the pre-operative Karnofsky performance score of 70-80
      vs. 90% as a prognostic factor for outcome (p = 0.001, risk ratio 3.62), but not
      age, gender, tumour volume, length of disease before treatment, mode of
      implantation, or major vs. moderate or no shrinkage of tumour volume after
      interstitial radiosurgery. Thus, 125-iodine radiosurgery yielded survival rates
      in these deep-seated insular gliomas comparable to those reported after surgery
      and radiation therapy of lobar tumours. This was achieved with a low peri
      operative mortality and morbidity and at low costs.

PMID- 7725952
TI  - Vitamin A, retinoids and breast cancer.
AB  - Both epidemiologic and experimental evidence are highly suggestive of an inverse
      relationship between vitamin A status and cancer induction. However, protection
      by vitamin A and retinoids has not been a universal finding, nor are the
      compounds equally effective in inhibiting cancer induction at all organ sites.
      Although the experimental evidence for a protective effect of retinoids is
      especially strong for mammary cancer, the epidemiologic evidence is less
      convincing. Chronic pharmacologic administration of retinoids may be limited by
      their potential toxicity; such potential toxicity is particularly important in
      light of the expectation that, in order to achieve effective anticarcinogenesis
      in a clinical setting, administration of retinoids may be required at relatively
      high doses for extended periods. Clinical trials to determine the efficacy of
      several retinoids as cancer preventive agents are only in the early stages.
      Meanwhile, experimentation to develop synthetic vitamin A analogs with increased
      activity, increased target organ specificity, and reduced toxicity must continue.
      The question of increasing anticarcinogenic activity by increasing vitamin A
      intake in populations whose vitamin A status is normal is more difficult to
      assess. The vast majority of epidemiologic studies indicate that groups with a
      relatively high intake of carotenoids are at a reduced risk for cancer in several
      target tissues. However, in populations whose vitamin A status is not deficient,
      increases in vitamin A and carotene intake are not well correlated with increases
      in serum vitamin A.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7725951
TI  - Proceedings of the 4th annual American Institute for Cancer Research conference
      on diet, nutrition and cancer. Washington, D.C., September 2-3, 1993.

PMID- 7725954
TI  - Dietary fat intake reduction for patients with resected breast cancer.

PMID- 7725953
TI  - Vitamin D adequacy: a possible relationship to breast cancer.
AB  - (1) Low levels of dietary calcium and vitamin D, biochemically interrelated,
      increase the promoting action of high dietary fat on chemically induced mammary
      carcinogenesis in animal studies. (2) High dietary fat increases mammary
      epithelial cell proliferation, particularly the "hormonally driven"
      hyperproliferation during breast growth and development in young animals.
      Increased dietary calcium (and probably vitamin D) lessens the increase of
      proliferation induced by high fat. These data, although limited, suggest that the
      maximum effect of diet (high fat increase, as well as calcium and vitamin D
      modulation) on eventual breast cancer may be during puberty, and adolescence,
      when the mammary gland is actively growing and developing. (3) An inverse
      epidemiological correlation has been developed between sunlight availability as a
      source of vitamin D and the risk of breast cancer in the U.S. and Canada. (4)
      Current vitamin D and calcium dietary intake in the U.S. is far below the RDA in
      all female age groups, particularly for the elderly. (5) Reduction of breast
      cancer risk, and simultaneously osteoporosis, might be achieved by increasing
      dietary intake of calcium and vitamin D to RDA levels. This may be particularly
      applicable to females during puberty and adolescence.

PMID- 7725955
TI  - Vitamin D and breast cancer.
AB  - 1. 1,25-Dihydroxyvitamin D3, the biologically active form of vitamin D, in
      addition to regulating calcium homeostasis, also has antiproliferative and
      prodifferentiating effects. 2. Most studies concerning the therapeutic potential
      of analogs of 1,25(OH)2D3, which are antiproliferative and prodifferentiating but
      do not cause hypercalcemia, have been done using leukemic cells. 3. Recent
      evidence from both in vivo and in vitro studies has indicated that 1,25(OH)2D3 or
      analogs of 1,25(OH)2D3 can inhibit the growth of breast cancer cells, thus
      suggesting the therapeutic potential of analogs of 1,25(OH)2D3 in the treatment
      of breast cancer.

PMID- 7725956
TI  - Some aspects of vitamin E related to humans and breast cancer prevention.
AB  - The biological activities of vitamin E are related to the cellular functions and
      presence of sufficient tissue concentrations of this micronutrient. Most of the
      stored vitamin E is in the adipose tissue where it appears to be distributed
      equally. The breast adipose tissue has similar vitamin E concentrations as other
      parts of the body. The ductal systems also store vitamin E in sufficient
      concentrations to maintain cellular functions. The milk secreted from the ducts
      of the breast contains a high concentration of tocopherol. Whereas the normal
      breast tissue presumably utilizes vitamin E as an antioxidant, tumor tissue
      appears to handle vitamin E differently. Breast tumors possessing estrogen
      negative receptors and having poor histological differentiation have lower
      concentrations of vitamin E than tumors with positive estrogen receptors and well
      differentiated histology. Since vitamin E is considered the principal, if not
      sole, chain-breaking lipophilic antioxidant in plasma and tissue, its role as a
      potential chemopreventive agent in breast cancer should be further investigated.
      The combination of vitamin E with other cancer chemopreventive agents appears to
      be a reasonable procedure.

PMID- 7725957
TI  - Dietary fat reduction as a hypothesis for the prevention of postmenopausal breast
      cancer, and a discussion of hypothesis testing research strategies.

PMID- 7725958
TI  - Hormone studies and the diet and breast cancer connection.

PMID- 7725959
TI  - Dietary fat effects on animal models of breast cancer.

PMID- 7725960
TI  - Effect of conjugated linoleic acid on carcinogenesis.

PMID- 7725961
TI  - A possible mechanism by which dietary fat can alter tumorigenesis: lipid
      modulation of macrophages function.
AB  - It has been known for at least 20 years that fatty acids can alter immune
      functions in vitro. More recently we have begun to understand the role that
      dietary fats play in immunity [formula: see text] and specifically how they may
      alter macrophage function. In the future it will be important not simply to
      redefine that fatty acids can alter select macrophage functions but to understand
      the mechanisms by which that occurs. Whether the same or different mechanisms are
      operational for those functions that are altered by dietary fat remains to be
      determined. Nevertheless, tumoricidal responses can be modified depending on the
      fatty acids in the diet. Hopefully, these recent observations will expand our
      understanding of how lipids regulate macrophage tumoricidal function and thus,
      might lead to new insights of how dietary fat may be manipulated to affect breast
      tumor regression.

PMID- 7725963
TI  - Meta-analysis of animal experiments: elucidating relationships between dietary
      fat and mammary tumor development in rodents.

PMID- 7725962
TI  - Dietary fatty acids and human breast cancer cell growth, invasion, and
      metastasis.

PMID- 7725964
TI  - Dimaprit--[S-[3-(N,N-dimethylamino)propyl]isothiourea]--a highly specific
      histamine H2-receptor agonist. Part 1. Pharmacology. 1977.

PMID- 7725965
TI  - Dimaprit, [S-[3-(N,N-dimethylamino)propyl]isothiourea]. A highly specific
      histamine H2-receptor agonist. Part 2. Structure-activity considerations. 1977.

PMID- 7725966
TI  - Evaluation of the CNS properties of SCH 29851, a potential non-sedating
      antihistamine. 1984.

PMID- 7725967
TI  - The pharmacology of slow reacting substance C and of arachidonic acid. 1973.

PMID- 7725969
TI  - Inhibition of arachidonic acid cyclo-oxygenase and lipoxygenase activities of
      leukocytes by indomethacin and compound BW755C. 1980.

PMID- 7725968
TI  - FPL 55712--an antagonist of slow reacting substance of anaphylaxis (SRS-A): a
      review. 1979.

PMID- 7725970
TI  - Biological effects of cyclosporin A: a new antilymphocytic agent. 1976.

PMID- 7725971
TI  - Thapsigargin, a novel molecular probe for studying intracellular calcium release
      and storage. 1989.

PMID- 7725973
TI  - Salazopyrin in rheumatoid arthritis. 1978.

PMID- 7725974
TI  - Induction of collagenase synthesis in chondrocytes by a factor synthesized by
      inflamed synovial tissue. 1984.

PMID- 7725972
TI  - The possible role of neutrophil proteinases in damage to articular cartilage.
      1978.

PMID- 7725975
TI  - The avian microcrystal arthritis II. Central versus peripheral effects of sodium
      salicylate, acetaminophen and colchicine. 1974.

PMID- 7725976
TI  - How aspirin might work: a pharmacokinetic approach. 1974.

PMID- 7725977
TI  - Calcium pyrophosphate-induced pleurisy in rats: a new model of acute
      inflammation. 1975.

PMID- 7725978
TI  - Inhibition of 5-hydroxytryptamine-induced and -amplified human platelet
      aggregation by ketanserin (R 41,468), a selective 5-HT2-receptor antagonist.
      1982.

PMID- 7725979
TI  - Notes and documents concerning the discovery of LSD. 1970.

PMID- 7725980
TI  - The discovery of librium. 1972.

PMID- 7725981
TI  - A brief survey of the history of inflammation. 1978.

PMID- 7725982
TI  - Metiamide--an orally active histamine H2-receptor antagonist. 1973.

PMID- 7725984
TI  - Evaluation of renal function before and after intravenous injection of non
      cholangiographic water soluble contrast media in rats.
AB  - In the present study, normal laboratory rats (n = 22), were injected
      intravenously with water soluble contrast media (CM) or saline. Renal function
      was monitored before and followed after challenge. Seven animals were injected
      with saline, the others with 3 different types of contrast media. The absolute
      urinary creatinine output decreased significantly in the saline group, from
      0.0247 mumol/min 100 g BW (IR: 0.0052) to 0.0167 mumol/min 100 g BW (IR: 0.0019)
      (p < 0.01), while in the CM groups only a significant decrease was seen after
      ioxaglate injection, from 0.0250 mumol/min 100 g BW (IR: 0.0014) to 0.0174
      mumol/min 100 g BW (IR: 0.0027) (p < 0.01). ANOVA between the groups showed no
      difference. The median values for serum creatinine after injection of the test
      products did not differ from the control values. It seems therefore that the
      challenge of a normal laboratory rat with CM is not a suitable model for the
      detection of subtile nephrotoxic properties of CM.

PMID- 7725985
TI  - Papillary cystadenoma of the epididymis: a case report.
AB  - In this report a case of bilateral papillary cystadenoma of the epididymis is
      described, a tumor associated with the Von Hippel-Lindau's disease
      (cerebelloretinal hemangioblastomatosis). Reports about the Von Hippel-Lindau's
      disease do only infrequently mention epididymal adenomas because the latter is
      mostly not associated with any symptoms. Retinal angiomatosis, cerebellar
      hemagioblastoma, pheochromocytoma and renal cell carcinoma are the lesions in the
      Von Hippel-Lindau's disease which cause symptoms and as a consequence disease.
      Because of some histological similarities between papillary cystadenoma and the
      clear cell type of renal adenocarcinoma a metastasis of a renal cell carcinoma
      has to be added to the list of differential diagnosis in case of an epididymal
      benign tumor apart from adenomatoid tumor, fibroma, lipoma,... The epididymal
      papillary cystadenoma, which is the only known benign epididymal tumor of
      epithelial origin, is considered a hereditary hamartoma. The precise histogenetic
      origin is still controversial.

PMID- 7725986
TI  - [Xanthogranulomatous pyelonephritis. Apropos of 11 cases].
AB  - Xanthogranulomatous pyelonephritis is a rare manifestation of chronic
      pyelonephritis. 11 cases were treated between 1988 and 1993. Patients age ranged
      from 17 to 60 years (mean 34 j). A pseudotumoral form was documented in 3
      patients and pyonephrosis was found in 8 cases. Urine culture was usually
      positive for a non specific germ. Imaging technics could differentiate
      pseudotumoral disease from diffuse disease. Treatment consisted in a nephrectomy.

PMID- 7725983
TI  - Classification and biological distribution of histamine receptor sub-types. 1975.

PMID- 7725987
TI  - [Renal oncocytoma. Apropos of a new case. Diagnostic and therapeutic problems].
AB  - The authors report a case of renal oncocytoma. Ultrasonographic and C.T. imaging
      has considerably simplified a preoperative diagnosis of this rare renal tumor;
      true diagnosis was only confirmed by histological examination. Surgical treatment
      counted in radical nephrectomy.

PMID- 7725989
TI  - [Renal adenocarcinoma and radical nephrectomy].
AB  - 74 cases of radical nephrectomy for adenocarcinoma are reported. The authors
      review the clinical aspects and the accuracy of imaging and insist on fortuitous
      detection of early stages by ultrasound. Survival is studied with regard to tumor
      stage, transfusion and cell type.

PMID- 7725988
TI  - [Efficacy of Doppler color echography in the diagnosis of caverno-venous leakage
      in the impotent patient].
AB  - Duplex sonography is now the gold standard for the non-invasive study of
      cavernous arteries. Many authors consider that this technique allows for the
      exploration of the veno-occlusive system and can detect venous leakage. The most
      common criteria is an end diastolic velocity > 5 cm/s, measured in the cavernous
      arteries. In a retrospective study, 34 impotent patients were reviewed. All of
      them were explored both by doppler sonography and pharmacocavernosometry to
      assess the efficacy of duplex sonography in detecting venous leakage. The data
      show that the doppler detects venous leakage in only 41%. The specificity and the
      sensitivity are both 50% which is clearly disappointing. Therefore, in our
      experience, duplex sonography is not a reliable technique to detect venous
      leakage. We consider that the best method is still pharmacocavernosometry.

PMID- 7725990
TI  - [Value of urodynamic studies in the framework of total radical prostatectomy].
AB  - In the service, sixty patients underwent a radical prostatectomy between 1987 and
      1994. The last 35 candidates to radical prostatectomy were prospectively analyzed
      in urodynamic parameters preoperatively and two months afterwards. Five patients
      present an incontinence: two total incontinence and three moderate incontinence.
      In two of the patients there was a detrusor instability, in two others an
      urethral instability and in the last patient, we discover a diminution of the
      bladder functional capacity on the postoperative urodynamics. So, the question is
      now to determine if incontinence is only caused by a sphincteric insufficiency or
      by a bladder or urethral dysfunction. The preoperative urodynamics are important
      to appreciate the quality of sphincters and the quality of the bladder; it's also
      an important meeting between the patient and the surgeon. The postoperative
      urodynamics seem to be reserved to the patients who have some problems, so to
      search an explanation for the incontinence. All our patients underwent
      rehabilitative physiotherapy, which seems to help them to recover their
      continence.

PMID- 7725993
TI  - [Relationship between intrapenile O2 lever and quantity of intracavernous smooth
      muscle fibers: current physiopathological concept].
AB  - Intracavernous PO2 (mm Hg) was measured during flaccidity in 5 psychogenic
      impotent patients (control), in 9 patients with venous leak and in 10 patients
      with arterial disease. No significant difference was observed in the mean PO2
      value between the control group 36.2 +/- 5.8 and patients with venous leak 35.6
      +/- 6.9 or with arterial disease 34.1 +/- 6.5 at flaccidity. Ten minutes after
      injection of Prostaglandin E1 (PGE1), the mean value of cavernous PO2 in the
      control group 83.8 +/- 6.8 was significantly different (p < 0.01) from that in
      the venous group 67.8 +/- 8.2 and the arterial group 57.8 +/- 10.7 (p < 0.01).
      Using the computerized analysis and the immunohistochemical staining actin anti
      actin, the mean percentage of cavernous smooth fibers was 43.3 +/- 3.6, 34.1 +/-
      4.6, and 29.3 +/- 3.4 in the three groups of patients respectively. At
      flaccidity, the higher the PO2 value, the higher the percentage of cavernous
      smooth muscle fibers was detected (p < 0.05). A high correlation was observed
      between the increase in PO2 value after injection of PGE1 and the increase in
      cavernous smooth muscle content. On the other hand, the mean value of penile
      brachial index in the psychogenic 0.87 +/- 0.07 was significant different (p <
      0.01) from the venogenic group 0.68 +/- 0.06 and the arteriogenic group 0.64 +/-
      0.09 (p < 0.01). Similarly, a high correlation was detected between the increase
      in penile brachial index ratio and the increase in cavernous smooth muscle
      content. A decrease in the percentage of the intracavernous smooth muscle fibers
      could be explained by the low oxygen tension at flaccidity and therefore could be
      responsible for insufficient rigidity during erection.

PMID- 7725991
TI  - [Epipadiac duplication of the urethra].
AB  - Urethral duplication is a less frequent malformation. The Williams
      classification, which is currently admit, classifies them in sagital, hypospadias
      or complex and collateral duplications. They can be complete, incomplete or
      reduced to an incomplete sinus. The most severe cases are often accompanied by
      multi-abnormality syndromes. Clinical manifestations are various: asymptomatic,
      urinary infection, incontinence, double urinary stream,... We will report two new
      cases of incomplete epispadias duplication. The first case presents a purulent
      flow from the fistula, the second a frank epispadiac status. In both cases,
      corrective surgical treatment was performed, after a complete balance-sheet. The
      embryological, diagnostical and therapeutical aspects of the different forms of
      urethral duplication will be studied based on data from literature.

PMID- 7725992
TI  - [Percutaneous treatment of tumors of the upper urinary tract].
AB  - In our Institution, 23 patients were selected for percutaneous resection of
      tumors of the upper urinary tract. Two patients underwent a second procedure: the
      first for ipsilateral recur and the second for an heterolateral tumor. Among
      these 23 patients, 11 presented a benign tumor, 9 were treated for a transitional
      carcinoma of whom 2 invasive state. Both underwent a nephro-ureterectomy. For the
      7 superficial transitional carcinomas, the mean follow-up period is 30.4 months.
      The ipsilateral local recurrencee is 14.3% (1/7), and concern a poorly
      differentiated tumor (G III). The advantage of the endoscopic techniques to
      explore and treat the upper urinary tract tumors is double. With these
      techniques, we can diagnose and treat adequately benign tumors which don't
      justify radical surgery. In the case of transitional tumors, the percutaneous way
      is an acceptable method of management when it appears better to avoid a radical
      treatment (solitary kidney, bilateral synchronous tumors, impairment of total
      renal function, general injuries). However, it must be performed only in selected
      cases, and patients should be carefully selected.

PMID- 7725994
TI  - [Bladder tumors: current prognostic factors].

PMID- 7725995
TI  - [Preliminary results of extracorporeal lithotripsy under local anesthesia using a
      multimodal generator (Tri-gen Compact Direx C)].
AB  - From April till October 1994, 64 patients were treated with the new generation of
      Direx lithotriptors, the Trigen Compact. The treatment was given in one-day
      clinic. The preparation is made of an intravenous hydratation, Dipidolor intra
      muscular, Voltaren intra-rectal and Emla on the skin in the area of the shocks.
      Only 38 patients are estimated at three months. The first results are
      encouraging, with globally 78% of good results (stone free or residual fragments
      inferior to 5 mm) and 22% of failure. The best results (90%) are obtained with
      the ureteral stones. The results of the treatments of caliceal and pyelo
      lithiasis are a little bit less good, with respectively 78 and 71% of good
      results. These data should become better when all the patients will be estimated
      at 3 months.

PMID- 7725999
TI  - Studies on the immune response of foot-and-mouth disease vaccine type Asia-1 in
      pregnant ewes, lambs and evaluation of type O vaccine by challenge.
AB  - Seven pregnant ewes at the 10th to 12th week of pregnancy were vaccinated with
      foot-and-mouth disease (FMD) vaccine type Asia-1. All pregnant animals responded
      well with antibody production without any adverse effects. The maximum antibody
      titer was noted 3 to 4 weeks after the vaccination. In the colostrum a high level
      of maternal antibodies persisted from 12 hrs to 6 weeks after birth. Irrespective
      of the presence of the maternal antibodies, the vaccinated lambs responded with
      antibody production within the first week of vaccination. The antibodies
      persisted up to the 12th week of vaccination. In another experiment five sheep
      were vaccinated with FMD type O vaccine and challenged with 10,000 TCID50 of
      virulent type O cell culture-adapted virus. The antibody titers in the vaccinated
      animals prior to challenge ranged between 1.26 to 1.65, while the four control
      sheep remained free from detectable antibody against virus type O. Pyrexia and
      viraemia developed present in all the control sheep but were absent in the
      vaccinated ones. Characteristic primary lesions on the dorsum of the tongue were
      observed after 48 hrs of virus challenge in the control sheep but were absent in
      the vaccinated ones.

PMID- 7725996
TI  - [Penile prosthesis in case of impotence: 12 years of clinical experience].
AB  - Among 95 patients who have received a penile prosthesis between 1982 and 1993
      (mean follow up of 46 months), 21 (22%) presented complications requiring one or
      more reintervention(s). Only for two patients the problem was mechanical, in the
      majority, they were non mechanical. Five of those subjects (5.5%) presented such
      complications that definitive explanation of the device was necessary. The
      problems presented by the 9 remaining patients were fully satisfactorily managed.
      Presently 94.5 per cent of the patients are using the device. Follow-up study of
      our interdisciplinary group demonstrates the efficacity of the prosthesis for
      revitalisation of the couples. The definitive parameters of implantation
      acceptance are essentially the partner influence and the treatment cost. This
      clinical study shows that the implantation of a penile prosthesis is an effective
      therapy in the treatment of impotence in a selected population. Presently, the
      mechanical reliability of different device has been good to date.

PMID- 7725998
TI  - In vitro infection of mouse pancreatic islet cells with coxsackie viruses.
AB  - We have demonstrated the ability of 4 standard coxsackie viruses (B4, B5, A7, and
      A9) and one fresh isolate (A7) from a newly diabetic child with homologous
      serological response, to infect in vitro grown mouse pancreatic islet cells. Up
      to the 9th day after infection the multiplication of viruses in the cells was
      proved using virus titration and immunofluorescence test. Isolated pancreatic
      cells proved to be a suitable model for detailed studies of experimental
      infection of pancreatic cells with coxsackie viruses.

PMID- 7725997
TI  - Transduction of imipenem resistance by the phage F-116 from a nosocomial strain
      of Pseudomonas aeruginosa isolated in Slovakia.
AB  - Generalized transducting Pseudomonas aeruginosa phage F-116 was propagated in an
      Imipenem (IMI)-resistant clinical isolate of P. aeruginosa No. 191 and the phage
      was then used to transduce the IMI-resistance to a susceptible auxotrophic mutant
      strain of the same species. Transduction seems to be a suitable method for study
      of resistance determinant(s) and mechanism of resistance in this important
      species. It was found that the IMI-resistance of the clinical strain No. 191 is
      caused by production of a betalactamase specifically hydrolyzing this antibiotic.

PMID- 7726000
TI  - Coxiella burnetii phase I and II proteins studied by SDS-page.
AB  - Coxiella burnetii cells in both phase I and II reveal in sodium dodecylsulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) similar protein profiles with only
      small differences. C. burnetii protein profile in SDS-PAGE depended on the method
      of purification of C. burnetii cells from chick embryo yolk sacs. Immune mouse
      sera against C. burnetii phase I cells recognized in phase I and II cell protein
      profiles mainly the 61 K and 29 K proteins by the immunoblot method. Hyperimmune
      mouse and rabbit sera against phase I and II cells reacted in different way with
      phase I and II cells. Sera against phase I cells recognized in both phase I and
      II profiles more protein bands than sera against phase II cells. Thus phase I LPS
      present in phase I cells exerted adjuvant effect on the antibody response in
      animals immunized with phase I cells.

PMID- 7726001
TI  - Differential tropism of EB rotavirus (serotype 3) to small intestine of
      homologous murine model.
AB  - The 4-5 days-old NMRI strain infant mice were orally inoculated with EB rotavirus
      (serotype 3). The intestinal disaccharidases activity was studied separately in
      three segments of the small intestine i.e. duodenum, jejunum and ileum on day 1
      to 7 post inoculation (p.i.). The severity of EB rotavirus infection correlated
      with a significant decrease of small intestinal lactase, maltase and sucrase on
      day 3 p.i. The level of maltase after the initial decline increased in all the
      three segments of small intestine of infected mice. However, the lactase activity
      remained suppressed for a relatively longer period in ileum of infected mice than
      in controls. These enzymes began to approach to normal value by day 5 p.i., but
      in ileum, lactase activity continued to be severely depressed even on day 7 p.i.
      Rotavirus was consistently detected in intestinal contents by ELISA on days 1 to
      7 p.i. The infected mice showed a significant increase in rotavirus (serotype 3)
      specific serum IgG and IgM antibody level during the declining (days 5-7 p.i.)
      phase of infection. Diarrhoea was noted up to day 6 p.i. The protracted
      suppression of the lactase activity in ileum in comparison to duodenum and
      jejunum showed a differential tropism of EB rotavirus (serotype 3) strain to the
      small intestine of homologous murine model.

PMID- 7726003
TI  - Tunis virus: a new Phlebovirus from Argas reflexus hermanni ticks in Tunisia.
AB  - A new Phlebovirus provisionally named Tunis virus has been isolated from Argas
      reflexus hermanni ticks parasitizing domestic pigeons. It is the first isolation
      of an arbovirus from Tunisia and the fourth tick-borne virus to be isolated from
      the Moghreb following Soldado, Essaouira and Kala Iris in Morocco. The pathogenic
      potential of this virus is briefly discussed according to the behaviour of its
      vector and previous serosurveys in the country.

PMID- 7726002
TI  - Factors affecting the sensitivity and reproducibility of passive
      haemagglutination test for the quantitation of measles-specific antibodies.
AB  - Various factors affecting the passive haemagglutination test (PHA) for the
      quantitation of measles-specific antibodies have been evaluated with the aim to
      obtain maximum sensitivity and reproducibility of the test. The antigen used for
      sensitization was prepared in Vero cells using Edmonston 245 strain of measles
      virus. Sheep red blood cells (SRBCs) were found most sensitive for use in PHA
      test. The optimum dilution of tannic acid was found to be 1:40,000 for tanning of
      fixed and 1:10,000 for unfixed SRBCs, when the tanning was carried out at 4
      degrees C overnight. Fixed and tanned SRBCs sensitized with 32 HA units of
      measles HA antigen at 56 degrees C for 30 mins were found optimal. SRBCs from
      different sheep affected the sensitivity of the assay. Stability study of SRBCs
      showed that storage at -70 degrees C of glutaraldehyde-fixed and sensitized SRBCs
      gave better results as compared to those stored at -20 degrees C and +4 degrees
      C. Tanned SRBCs could be stored at -70 degrees C only up to 15 days. Sensitized
      SRBCs with-stood two cycles of freezing and thawing after removal from -20
      degrees C and -70 degrees C. Sensitized SRBCs could be stored for 120 days
      without any significant loss of titer at -20 degrees C, +4 degrees C or 22
      degrees C; when lyophilized with stabilizers, there was a slight decline in the
      titer after exposure at 37 degrees C for 30 days. The lyophilized sensitized
      SRBCs after reconstitution were found to be stable at +4 degrees C for 3 days
      without any loss in the titer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726004
TI  - Plaque assay for Spodoptera exigua and Autographa californica nuclear
      polyhedrosis viruses in a newly established cell line of the beet armyworm,
      Spodoptera exigua.
AB  - The nuclear polyhedrosis viruses of Spodoptera exigua (SeNPV) and Autographa
      californica (AcNPV) produced plaques in a newly established cell line of the beet
      armyworm, Spodoptera exigua. Plaques were composed of infected cells containing
      many polyhedra and were visible without any staining procedure. Dose-response
      assays showed a direct correlation between the number of plaques and the inoculum
      size. Growth kinetic studies of the two viruses, using the developed plaque assay
      system, revealed that the release of extracellular viruses began 6 hrs post
      infection (p.i.) and the titer reached a plateau 48 hrs p.i. The sensitivity of
      this plaque assay system was 100 times greater for the heterologous AcNPV than
      for the homologous SeNPV.

PMID- 7726005
TI  - Serological evidence of Hantaan virus in Slovakia during 1989-1991.
AB  - Nephropathia epidemica was supposed to be an European form of haemorrhagic fever
      with renal syndrome (HFRS). However, in 1989-1991 we found serological evidence
      of infection with Hantaan virus in patients' sera from Slovakia. Higher titers of
      antibodies against Hantaan virus were detected in sera of 6 out of 75 patients
      with febrile disease, renal failure and clinical diagnosis of HFRS. The higher
      titers of antibodies against Puumala virus were detected in sera of 6 out of 75
      patients. Serologic differentiation between Hantaan and Puumala infection in
      patients was based on the detection of higher antibody titers (4-fold or greater
      differences).

PMID- 7726007
TI  - The inflammatory and immune response to mousepox (infectious ectromelia) virus.
AB  - The ectromelia virus (EV) has been recognized as the etiological agent of a
      relatively common infection in laboratory mouse colonies around the world, i.e.,
      Europe (including Poland), USA and Asia. Due to widespread use of mice in
      biomedical research, it is important to study the biology of strains
      characteristic for a given country. This is particularly significant for the
      diagnosis, prevention and control ectromelia. In severe epizootics, approximately
      90% morbidity is observed within colonies and mortality rate exceeding 70% is
      observed within 4 to 20 days from the appearance of clinical symptoms. The
      resistance to lethal infection is mouse strain-dependent. Several inbred strains
      of mice, including C57BL/6 and AKR are resistant to the lethal effects of EV
      infection, while others, such as A and BALB/c are susceptible. Recent studies
      indicate that (1) T lymphocytes, NK cells and interferon (IFN)-dependent host
      defenses must operate for the expression of resistance, (2) virus-specific T-cell
      precursors appear earlier in regional lymph nodes of resistant than susceptible
      mice, and (3) resistance mechanisms are expressed during early stages of
      infection. Over the past several years, (1) induction of anti-EV cytotoxic CD8+ T
      lymphocytes (CTL) responses in vivo in the absence of CD4+ (T helper) cells, (2)
      importance of some cytokines e.g., IFN-gamma in EV clearance at all stages of
      infection, and (3) induction of nitric oxide (NO) synthase, which is necessary
      for a substantial antiviral activity of IFN-gamma, have been
      demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726006
TI  - Identification of an amino acid substitution involved in the reduction of
      sensitivity of HIV-1 to an inhibitor of viral proteinase.
AB  - Clones derived from HIV variants previously characterized as resistant to Ro31
      8959, an inhibitor of viral proteinase (PR), were sequenced. Substitution of
      glycine by valine at position 48 of the PR protein was found. None of the 20
      clones derived from wild type HTLV-IIIB contain this mutation. Since such a
      position is located in a conserved region of PR, it is possible that the
      substitution can affect the interaction of the enzyme with the inhibitor.

PMID- 7726008
TI  - A herpesvirus from an European shrew (Crocidura russula)

PMID- 7726009
TI  - Percutaneous transfemoral repositioning of malpositioned central venous
      catheters.
AB  - Central venous catheters inserted by blind surgical placement may not advance
      into a satisfactory position and may require repositioning. Malpositioning via
      surgical insertion is common in patients in whom central venous catheters have
      previously been placed, as these patients are more likely to have central venous
      thrombosis and distortion of central venous anatomy. This is less of a problem
      when catheter placement is guided by imaging; however, even when insertion is
      satisfactory, central venous catheters may become displaced spontaneously after
      insertion (Fig. 1). Repositioning can be effected by direct manipulation using
      guidewires or tip-deflecting wires [1, 2], by manipulation via a transfemoral
      venous approach [3-5], and by injection of contrast material or saline [6].
      Limitations of the direct approach include (1) the number and type of maneuvers
      that can be performed to effect repositioning when anatomy is distorted, (2)
      difficulty in accessing the catheter, and (3) the risk of introducing infection.
      Moreover, these patients are often immunosuppressed, and there is a risk of
      introducing infection by exposing and directly manipulating the venous catheter.
      Vigorous injection of contrast material or saline may be unsuccessful for the
      same reasons: It seldom exerts sufficient force to reposition large-caliber
      central venous catheters and may cause vessel damage or rupture if injection is
      made into a small or thrombosed vessel. We illustrate several alternative methods
      for catheter repositioning via a transfemoral venous approach.

PMID- 7726010
TI  - Manuscript peer review at the AJR: facts, figures, and quality assessment.
AB  - Concern by the government, funding institutions, and the public for quality
      assurance in all aspects of medical endeavors mandates critical examination of
      various professional activities. Although peer review is generally regarded as
      the best system for selecting and improving scientific papers for publication,
      the efficacy of this process has never been proved. Moreover, the administrative
      functions of the editorial staff are often poorly understood. The purpose of this
      article is to make peer review a the AJR less esoteric and more understandable by
      quantifying some of its activities. This information is then assessed as it
      relates to the quality of this important step in scientific publication.

PMID- 7726013
TI  - Is helical CT more accurate or more sensitive at finding clots than the
      radionuclide study?

PMID- 7726011
TI  - The rise and fall of a radiologic technique.
AB  - As young radiologists read the slightly self-satisfied articles celebrating the
      centennial of radiology, they may conclude that the course of radiology and all
      its components has been smoothly upward, without hesitations, false starts, or
      disappointments. Older radiologists know better. The replacement of a less
      satisfactory technique with a better one is a gain for both patients and
      physicians, but the replacement process itself can be distressing. Much of what
      radiology residents learned in the 1950s and 1960s is no longer of any use. Who
      now employs pneumoencephalography or intravenous cholangiography? Entire books
      were once written about these procedures [1, 2]. Who can now credit the reliance
      once placed on positive-contrast maxillary antrography [3]? Few have even heard
      of eustachian tubography [4]. Radiologists who tried to make a career using those
      techniques learned to their sorrow that although anatomy is permanent and
      diseases change only slowly, techniques are often ephemeral. Total body
      opacification, a technique once of consuming interest to the present writers [5
      7], is an illustration of this.

PMID- 7726012
TI  - American martyrs to radiology. Wolfram Conrad Fuchs (1865-1908). 1936.

PMID- 7726014
TI  - Cluster of calcifications in mammographic screening.

PMID- 7726015
TI  - Pelvic sonogram.

PMID- 7726016
TI  - Small masses in the kidney.

PMID- 7726017
TI  - What are the optimal MR pulse sequences for the detection of intramedullary
      spinal cord lesions?

PMID- 7726018
TI  - A radiologist's guide to Australian history.

PMID- 7726019
TI  - Paleoradiology and European colonization.

PMID- 7726020
TI  - Keloids of the breast: mammographic findings.

PMID- 7726021
TI  - Sonographically guided core-needle biopsy of breast masses: the "bayonet
      artifact".

PMID- 7726022
TI  - Intrarenal arterial Doppler sonography in the detection of renal vein thrombosis
      of the native kidney.

PMID- 7726023
TI  - Extracorporeal liver and spleen in gastroschisis.

PMID- 7726024
TI  - Abnormalities of the bladder in children: imaging findings.

PMID- 7726025
TI  - Tailored low-dose fluoroscopic voiding cystourethrography for the reevaluation of
      vesicoureteral reflux in girls.

PMID- 7726026
TI  - Cord compression by extramedullary hematopoiesis in polycythemia vera.

PMID- 7726027
TI  - Proximal involvement of vertebral artery in fibromuscular dysplasia.

PMID- 7726028
TI  - How many radiologists will be needed in the years 2000 and 2010? Projections
      based on estimates of future supply and demand.
AB  - Predicting the appropriate number of diagnostic radiologists needed in the United
      States for the next decade is an important but difficult task. Previous attempts
      have been characterized by incomplete data, conflicting results, and ultimately,
      as the future revealed itself, erroneous conclusions [1-3]. Nonetheless, with
      major changes expected in health care, estimation of physician workforce needs is
      perhaps more critical than ever before. In this study, both the future supply of
      diagnostic radiologists and the demand for diagnostic radiology services in the
      United States were analyzed. Projected supply of diagnostic radiologists was
      calculated by using data about the number presently in practice, the current
      number of radiology residents, and the rate at which diagnostic radiologists
      leave the profession through either retirement or death. Demand for radiologic
      services in the future was evaluated by estimating effects of possible changes in
      population and demography, health care reform, technology, universal health
      insurance, and women in radiology.

PMID- 7726029
TI  - We've got that durned influenzy agin.

PMID- 7726030
TI  - Recent insights into the etiology and pathogenesis of acute biliary pancreatitis.

PMID- 7726031
TI  - Cyst fluid analysis and imaging of pancreatic cystic lesions.

PMID- 7726032
TI  - Transcatheter treatment of thrombosed hemodialysis access grafts.
AB  - Thrombosis of access grafts is a frequent problem for patients being treated with
      long-term hemodialysis. Transcatheter techniques have recently been used in the
      primary management of failed dialysis grafts. This article reviews current
      methods for transcatheter treatment. Several thrombolytic techniques are
      discussed, including pharmacologic, pharmacomechanical, and mechanical methods.
      Methods for treatment of underlying graft stenosis are considered. Complications
      associated with these procedures are reviewed. The percutaneous techniques are
      compared among themselves and with standard surgical procedures for graft
      revision. Finally, several evolving methods for prevention of dialysis graft
      thrombosis are considered.

PMID- 7726033
TI  - Regional alterations in lung ventilation in end-stage primary pulmonary
      hypertension: correlation between CT and scintigraphy.
AB  - OBJECTIVE: The purpose of this study was to correlate scintigraphic findings of
      regional alterations in lung ventilation and perfusion with regional variations
      in CT attenuation in patients with primary pulmonary hypertension. SUBJECTS AND
      METHODS: Chest CT scans and ventilation-perfusion scans obtained within 24 hr of
      each other in 18 patients with primary pulmonary hypertension referred for lung
      transplantation were reviewed. The lungs were divided into eight regions
      (left/right, superior/inferior relative to the carina, and anterior/posterior
      relative to the trachea). CT scans were evaluated and areas of parenchymal
      inhomogeneities were tabulated for the eight regions. Areas of reverse mismatch
      (perfusion without ventilation) were established by blinded analysis of planar
      scintigraphic studies in six projections using 99mTc-labeled DTPA-aerosol and
      macroaggregated albumin for the eight regions and then were correlated with the
      CT findings. RESULTS: Abnormal findings on ventilation scans and reverse
      ventilation-perfusion mismatches indicating an inadequate hypoxic
      vasoconstriction reflex were found in 91 regions in all 18 patients. Nonuniform
      parenchymal CT density was found in 12 patients. There was a significant
      correlation (p = .009) of scintigraphic reverse mismatches with abnormal CT
      density in 38 regions in 11 patients. In one patient, there was no scintigraphic
      correlation with abnormal CT attenuation. The specificity of abnormal CT density
      for scintigraphic reverse mismatches was 81%, with a sensitivity of 42%.
      CONCLUSION: Scintigraphic reverse mismatches indicate a high prevalence of
      significant pulmonary arterial shunting in patients with ventilatory defects.
      Increased relative CT attenuation in areas of impaired ventilation as shown on
      the ventilation scans is amplified in primary pulmonary hypertension by an
      inadequate hypoxic vasoconstriction reflex. This finding does not signify
      underlying infiltrative lung disease and correlates with regions with reverse
      mismatches.

PMID- 7726034
TI  - Comparison of hard- and soft-copy digital chest images with different matrix
      sizes for managing coronary care unit patients.
AB  - OBJECTIVE: This study was to determine whether different digital display formats
      for portable chest radiographs of coronary care unit patients would provide
      comparable information for clinical care. In particular, we tried to ascertain
      whether 1024 x 1024 pixel (1K) images on a picture archiving and communication
      system (PACS) workstation would be comparable to 1760 x 2140 pixel (2K) images on
      workstations or to digital films. If comparability could be proved, we
      hypothesized that 1K workstations could considerably lower equipment and film
      costs and facilitate image transmission from point to point. MATERIALS AND
      METHODS: Four chest radiologists read a panel of chest studies assembled from 98
      coronary care unit patients, comparing 1K and 2K soft-copy images with digital
      hard copies. For all three image types for the 98 patients, the readers evaluated
      nine image parameters that the cardiologists deemed essential for clinical
      decision making. Two other chest radiologists reviewed each patient's three image
      types, historical chest images, current and prior radiologic reports, and medical
      record to determine the consensus, or "truth findings." RESULTS: With one
      exception (small pleural effusions), the receiver operating characteristic
      analysis showed no significant differences in the clinical information derived
      from the three image types. CONCLUSION: For clinical management in a coronary
      care unit, comparable information can be obtained from digital radiologic chest
      studies using a 1K x 1K soft-copy format, a 2K x 2K soft-copy format, or a hard
      copy (film). Substantial savings in cost and time are therefore possible by using
      soft-copy images and lower resolution (1K x 1K) workstations and, when necessary,
      by transmitting images on regular telephone lines.

PMID- 7726035
TI  - Distension of extrapleural spaces with contrast medium or air: value in creating
      safe percutaneous access to the mediastinum in cadavers.
AB  - OBJECTIVE: We artificially widened the extrapleural space with contrast medium or
      air in 33 cadavers to create a safe extrapleural route to the anterior
      mediastinum and the posterior mediastinum for large-bore needle biopsies.
      MATERIAL AND METHODS: Under CT guidance, 120 ml of diluted contrast medium (10%)
      or 300 ml of air was injected percutaneously into the right paravertebral (n =
      23) and left retroaortic (n = 5) or ventral parasternal (n = 5) extrapleural
      spaces. RESULTS: In six of 18 cases, the paravertebral space was found to be wide
      enough to advance a 14-gauge cannula to the extrapleural paraesophageal space.
      After injection of 120 ml of diluted contrast medium, the width of the right
      paravertebral space at the level of the posterior rim of the vertebral body was
      dilated from a mean of 0.62 cm to 1.06 cm, and the width of the anterior rim was
      dilated from a mean of 0.91 cm to 1.97 cm. In 17 of 18 cases, the paravertebral
      space was wide enough to accommodate a 14-gauge cannula. A large osteophyte
      blocked the access route in one case. Artificial widening regresses within 7 min
      by an average of 33% at the level of the posterior rim of the vertebral body and
      by an average of 18% at the level of the anterior rim. Dilatation was
      significantly more effective with diluted contrast medium than with air. When 120
      ml of diluted contrast medium was injected into the left retroaortic extrapleural
      space, the distance between the aorta and the vertebral column was widened from a
      mean of 0.40 cm to 1.50 cm. Using a ventral approach for injecting 120 ml of
      solution, we widened the parasternal access route from a mean of 0.42 cm to 1.90
      cm. CONCLUSION: In this cadaver study, artificial dilatation of the mediastinum
      with diluted contrast medium allowed extrapleural access from right
      paravertebral, left retroaortic, and parasternal directions for large-bore needle
      biopsies.

PMID- 7726036
TI  - Cardiac myxoma: identification of intratumoral hemorrhage and calcification on MR
      images.

PMID- 7726037
TI  - Mammography of the male breast.
AB  - Mammography of the male breast accounts for less than 1% of mammographic
      examinations done in breast imaging centers [1]. The purpose of this pictorial
      essay is to familiarize readers with diseases of the male breast and their
      mammographic manifestations that were observed during a 40-month period at the VA
      Medical Center, West Los Angeles. The most common presenting signs and symptoms
      that lead to a request for a mammograph in these men included an enlarging
      breast, a palpable lump, and breast tenderness.

PMID- 7726038
TI  - Biliary sludge after liver transplantation: 1. Imaging findings and efficacy of
      various imaging procedures.
AB  - OBJECTIVE: Biliary sludge (inspissated, thickened bile or collective collagen
      tissue from destroyed [or necrotic] bile duct walls) can be found a few days to
      several years after liver transplantation, mainly in the common and main hepatic
      bile ducts. The purpose of this study was to review the imaging findings of
      biliary sludge occurring after liver transplantation and to determine the
      relative merits of various imaging procedures (cholangiography, CT, and
      sonography) for establishing the diagnosis. MATERIALS AND METHODS:
      Cholangiograms, sonograms, and CT scans obtained in 352 patients with 400 liver
      transplants were reviewed retrospectively for evidence of biliary sludge. In all
      patients, T-tube cholangiograms were routinely obtained 7 and 30 days and 3
      months after transplantation. Thereafter, in the absence of findings, the T-tube
      was removed. In all patients, sonograms were obtained immediately, 2 and 7 days
      after transplantation. Additional cholangiograms were obtained when biliary
      complications were suspected (T-tube cholangiograms in 215 patients, percutaneous
      transhepatic cholangiograms in 79 patients, and endoscopic retrograde
      cholangiograms in five patients after T-tube removal). Additional sonograms were
      obtained in 289 patients and CT scans in 238 patients when complications were
      suspected. The findings of these various imaging studies were analyzed and
      compared with each other, with the clinical course of the patient, and with
      surgical and histologic findings to determine the relative merits of each imaging
      method for the diagnosis of biliary sludge. Criteria for the diagnosis of biliary
      sludge were filling defects or pluglike obstruction seen on cholangiograms or
      material filling the bile ducts seen on sonograms or CT scans. The radiologic
      diagnosis of biliary sludge was certified by gross specimens obtained at surgery
      (n = 21) or autopsy (n = 2) or by complete disappearance of the radiologic
      findings with specific oral or interventional treatment (n = 28). RESULTS:
      Biliary sludge was diagnosed on the basis of radiologic findings in 51 (13%) of
      400 transplanted livers. Cholangiograms (T-tube in 34, percutaneous transhepatic
      cholangiography in seven, a combination of T-tube and percutaneous transhepatic
      cholangiography in eight, and a combination of endoscopic retrograde and
      percutaneous transhepatic cholangiography in two cases) showed biliary sludge in
      all 51 cases. Cholangiographic findings included filling defects in 34 (67%) and
      obstruction of the bile duct with pluglike appearance in 17 (33%) of the 51
      cases. Dilatation of bile ducts was present in 32 (63%) of the 51 cases. The
      presence of biliary sludge was certified in 50 of these cases, with one case
      turning out to be a sutural granuloma at autopsy. On sonograms, biliary sludge
      was shown as echogenic material in the main bile ducts in only 16 (31%) of the 51
      cases, with dilatation of bile ducts in 12 of them. In 10 others (20%), sonograms
      showed dilatation of the bile ducts but did not show the sludge itself. CT scans
      did not show the sludge in any of the 12 cases in which they were obtained.
      CONCLUSION: Our results show that cholangiography is the only accurate imaging
      method for diagnosing biliary sludge after liver transplantation. Sonography is
      limited and CT is of no value for this purpose. In the absence of a T-tube,
      endoscopic retrograde or percutaneous transhepatic cholangiography should be
      used. Otherwise, T-tube cholangiography is the method of choice. Filling defects
      and obstruction of the bile ducts with pluglike material are characteristic
      findings of biliary sludge seen on cholangiograms.

PMID- 7726039
TI  - Evaluation of the portal venous system before liver transplantation: value of
      phase-contrast MR angiography.
AB  - OBJECTIVE: The purpose of this study was to assess the accuracy of phase-contrast
      MR angiography with gadolinium in evaluating the patency and blood flow direction
      of the portal venous system; the presence, extent, and type of varices; and the
      patency of surgical decompressive shunts in patients before liver
      transplantation. This information is essential in management and care of patients
      with chronic liver disease and portal hypertension and those who are candidates
      for liver transplantation. SUBJECTS AND METHODS: Twenty-four patients with portal
      venous hypertension were evaluated with phase-contrast MR angiography. Two
      patients had surgical splenorenal shunts and one had a mesocaval shunt. Phase
      contrast angiograms were acquired as a series of two-dimensional sequential
      coronal sections during breath-holding and after IV administration of
      gadopentetate dimeglumine. Correlative findings from color flow Doppler
      sonography, contrast-enhanced CT scanning, and conventional angiography were
      available in 23, 20, and 10 patients, respectively, and were used as standards.
      The images from each technique were analyzed independently for patency of and
      flow direction in the portal vein, splenic vein, superior mesenteric vein, and
      surgically created shunts, and for detection, distribution, and extent of five
      variceal groups. RESULTS: Findings from phase-contrast MR angiography completely
      agreed with those of sonography, CT scanning, and conventional angiography. The
      main portal vein was patent in 18 patients, stenosed in one, partially thrombosed
      in one, and occluded in four. Phase-contrast MR angiography correctly showed
      hepatofugal flow in three patients and hepatopetal flow in 17 patients. Both the
      splenic and superior mesenteric veins were patent in 20, partially thrombosed in
      one, and occluded in three cases. Phase-contrast MR angiograms showed 85% of the
      variceal groups, and MR rating of variceal size was not significantly different
      from that of CT rating. Phase-contrast MR angiography correctly showed the
      patency of all three surgical decompressive shunts. CONCLUSION: Phase-contrast MR
      angiography is accurate for evaluating the patency and flow direction of the
      portal venous system, detecting and determining the distribution and extent of
      varices, and assessing the patency of surgically created shunts. Therefore, it is
      a reliable and noninvasive technique that can provide crucial information in the
      preoperative workup of liver transplant recipients.

PMID- 7726040
TI  - Dual-phase helical CT of the liver: value of arterial phase scans in the
      detection of small (< or = 1.5 cm) malignant hepatic neoplasms.
AB  - OBJECTIVE: Helical CT scanners now allow sequential arterial phase and portal
      venous phase scans of the entire liver to be obtained during a single bolus
      injection of contrast material. The purpose of this study was to determine if
      arterial phase scans improve detection of small (< or = 1.5 cm) malignant hepatic
      neoplasms when compared with portal venous scans alone. MATERIALS AND METHODS:
      Dual-phase helical CT of the liver was done in 96 patients referred for known or
      suspected malignant hepatic lesions. Malignant hepatic neoplasms were detected in
      38 patients (27 with at least one small neoplasm), one patient had undetected
      metastases, one patient had a benign hepatic neoplasm, and 56 patients had no
      hepatic neoplasm. Proof of individual neoplasms was based on biopsy results,
      surgical findings, or findings on other imaging studies (primarily follow-up CT).
      The absence of disease was established by surgical or autopsy findings, findings
      on subsequent imaging studies, or a combination of clinical and laboratory data.
      A total of 150 ml of 60% nonionic contrast material was infused at 5 ml/sec
      followed by sequential arterial phase and portal venous phase helical scans of
      the liver. Three radiologists retrospectively reviewed the scans. Individual
      lesions were measured and the conspicuity of each lesion on arterial phase and
      portal venous phase scans was compared. The percentage of patients in whom some
      malignant neoplasms were detected better on the arterial phase scan was
      calculated using categories based on lesion size and typical tumor vascularity.
      RESULTS: In 10 (37%) of 27 patients who had at least one small malignant
      neoplasm, lesions 1.5 cm or less in diameter were only visible or were more
      conspicuous on the arterial phase scan. No malignant neoplasms more than 1.5 cm
      in diameter were visible only on the arterial phase scan. In four (11%) of 38
      cases, malignant neoplasms more than 1.5 cm in diameter were more conspicuous on
      the arterial phase scan. The arterial phase scans improved lesion conspicuity in
      nine (39%) of 23 patients who had typically hypervascular neoplasms, whereas
      lesion conspicuity was improved in three (20%) of 15 patients who had typically
      hypovascular neoplasms (p = .02). The arterial phase scan resulted in the false
      positive detection of lesions in two (2%) of 96 cases. CONCLUSION: Arterial phase
      helical CT of the liver improves detection of some small, malignant hepatic
      neoplasms when performed in addition to portal venous scanning. The value is
      greatest in those patients who have hypervascular neoplasms.

PMID- 7726044
TI  - Feline esophagus.

PMID- 7726041
TI  - CT diagnosis of early hepatocellular carcinoma: sensitivity, findings, and CT
      pathologic correlation.
AB  - OBJECTIVE: The purpose of this study was to determine the sensitivity of CT in
      detecting early hepatocellular carcinoma and to evaluate its CT appearance. An
      early hepatocellular carcinoma is a nodular lesion with no fibrous capsule
      composed of well-differentiated tumor histologically. It differs from a small
      hepatocellular carcinoma, which is an overt tumor that is moderately to poorly
      differentiated and has a fibrous capsule. Size is not a criterion for
      distinguishing between early and small hepatocellular carcinomas. MATERIALS AND
      METHODS: Thirty-one patients with 39 histopathologically proved early
      hepatocellular carcinomas (mean diameter, 1.7 cm) found by sonography, MR
      imaging, and/or intraoperative sonography were included in a retrospective study.
      We reviewed unenhanced CT scans of the entire liver in 30 patients (37 lesions)
      and early and late (35 sec and 5 min after the beginning of injection of contrast
      material) contrast-enhanced CT scans of the entire liver in all 31 patients
      (table incremental CT in 21; helical CT in 10; 39 lesions). Eighteen
      histologically proved small hepatocellular carcinomas (< or = 3 cm; mean
      diameter, 2.3 cm), present in the same patients, served for comparison.
      Histopathologically, nine patients had chronic hepatitis, and 22 had cirrhosis.
      RESULTS: The overall sensitivity of CT in detecting early hepatocellular
      carcinoma was 56%. These tumors were usually isodense with respect to surrounding
      liver on unenhanced, early enhanced, and late enhanced CT scans (iso-iso-iso).
      This pattern was seen in 17 (46%) of 37 lesions; thus, these 17 histologically
      proved early hepatocellular carcinomas were not detected with CT. An iso-iso-low
      density pattern was recognized in eight (22%), a low-low-low pattern in seven
      (19%), and several different patterns in five (13%) of the 37 lesions. Only two
      (5%) of 39 early hepatocellular carcinomas had a high-density appearance on early
      enhanced CT scans. In comparison, the most common pattern of small overt
      hepatocellular carcinomas on CT scans was low-high-low, seen in 17 lesions (94%)
      detected with CT. When the density of lesions on unenhanced CT scans was compared
      with the histopathologic appearance of the masses, low-density lesions showed
      mild to moderate fatty change and isodense lesions showed no or minimal fatty
      change (p = .006). CONCLUSION: The sensitivity of CT in detecting early
      hepatocellular carcinoma is poor (56%). However, the diagnosis of early
      hepatocellular carcinoma should be considered if CT scans show a small lesion
      with an iso-low or low-low density enhancement pattern on early and late contrast
      enhanced CT scans, respectively, in patients with chronic liver disease.

PMID- 7726043
TI  - Strictures after gastric surgery: treatment with fluoroscopically guided balloon
      dilatation.
AB  - OBJECTIVE: Stricture formation resulting in impedance of gastric emptying is a
      relatively common complication after gastric surgery that involves anastomosis
      creation or pyloroplasty. Treatment of the stenosis with fluoroscopically guided
      balloon dilatation avoids further surgery. Accordingly, we report our experience
      with 32 dilating procedures in 24 consecutive patients who had the postoperative
      complication of obstruction at a surgically created gastric outlet. MATERIALS AND
      METHODS: Out of our series of approximately 650 fluoroscopically guided balloon
      dilatations, 32 procedures were performed on 24 patients with anastomotic
      strictures or pyloric narrowing after gastric surgery (vertical banded
      gastroplasty or gastric bypass surgery [n = 15], partial esophagectomy with
      esophagogastrostomy and pyloroplasty [n = 6], and partial gastrectomy with
      gastrojejunostomy [n = 3]). The group included 13 men and 11 women ranging from
      32 to 79 years old (mean, 51 years). Diameters of the balloons chosen ranged from
      10 to 20 mm, depending on the size of the surgically created anastomosis or
      pyloroplasty. Indications for balloon dilatation were clinical and radiographic
      evidence of gastric outlet obstruction. The procedures were done between 13 days
      and 10 years (mean, 14 months) after gastric surgery. The result of each
      procedure was assessed by evaluating clinical outcome (relief or recurrence of
      symptoms) during the follow-up period of 2 days to 36 months (mean, 8 months)
      after the procedure. RESULTS: In 17 of the 24 patients, the obstructive symptoms
      were treated successfully with a single dilatation procedure, and symptoms did
      not recur during follow-up ranging from 1 to 36 months (mean, 11 months). In the
      other seven patients, the procedure was considered unsuccessful because the
      patients experienced recurrent obstruction within 2 days to 13 weeks (mean, 3
      weeks) after the initial procedure. In one of these, symptoms were relieved by a
      second procedure. Repeat dilatations in the other six patients were unsuccessful,
      and all six eventually required surgical revision for definitive treatment. No
      complicating perforations were noted as a result of dilatation. CONCLUSION: Our
      experience shows that fluoroscopically guided balloon dilatation is a simple and
      safe technique for treating obstructive symptoms caused by strictures occurring
      after gastric surgery. In the majority of patients, symptoms are relieved with a
      single balloon dilatation, eliminating the need for further surgery. However,
      patients whose obstructive symptoms recur after the initial balloon dilatation
      procedure are less likely to benefit from further dilatations and usually require
      surgery.

PMID- 7726042
TI  - Distinction between postoperative ileus and mechanical small-bowel obstruction:
      value of CT compared with clinical and other radiographic findings.
AB  - OBJECTIVE: The expeditious diagnosis of complete and partial mechanical small
      bowel obstruction, as opposed to paralytic ileus, during the immediate
      postoperative period may be difficult on the basis of clinical and plain film
      radiographic findings. For this reason, we prospectively evaluated the use of CT
      in this setting and compared it with the clinical and plain film evaluations as
      well as with various contrast examinations. SUBJECTS AND METHODS: Thirty-six
      postoperative patients with signs and symptoms of paralytic ileus or mechanical
      small-bowel obstruction were examined clinically and had plain abdominal
      radiographs. Based on the findings of these examinations, the surgeon assigned
      patients to one of the following categories: (1) paralytic ileus, (2)
      indeterminate, (3) partial mechanical obstruction, or (4) complete mechanical
      obstruction. CT scans were obtained within 24 hr of the initial diagnostic
      studies, and patients were then recategorized according to the above
      classification solely based on CT findings. Initial examination results were then
      compared with the CT results. In addition, the results of contrast studies,
      namely, enteroclysis and barium enema, performed after CT small-bowel series,
      were evaluated. The gold standard for diagnosis was laparotomy in 20 patients,
      clinical course and follow-up in 13 patients, and clinical course and contrast
      studies in the other three patients. RESULTS: CT was effective (sensitivity and
      specificity, 100%) in distinguishing between postoperative ileus and complete
      mechanical small-bowel obstruction. The combined clinical and plain film findings
      were often confusing and nondiagnostic (sensitivity, 19%). CT was also valuable
      in diagnosing and distinguishing partial mechanical small-bowel obstruction from
      paralytic ileus. Contrast studies (enteroclysis) in four patients with partial
      mechanical small-bowel obstruction were useful in grading the degree and severity
      of the obstruction. CONCLUSION: Our results suggest that in the immediate
      postoperative period, CT is the method of choice for diagnosing mechanical small
      bowel obstruction and distinguishing it from paralytic ileus. Contrast studies
      are useful in further evaluating partial mechanical small-bowel obstruction.

PMID- 7726045
TI  - Ectopic gastric mucosa in the upper esophagus: prevalence and radiologic
      findings.
AB  - OBJECTIVE: Ectopic gastric mucosa of the upper esophagus is an asymptomatic
      benign lesion that may simulate a more serious lesion on radiographs. We studied
      the radiographic findings and prevalence of this abnormality. SUBJECTS AND
      METHODS: During a 1-year period, 1142 consecutive patients (817 men, 325 women)
      who had an upper gastrointestinal series as part of an annual health checkup were
      prospectively studied. Routine examination of the esophagus consisted only of
      fluoroscopy. Radiographs were obtained if any localized irregularities were found
      in the upper esophageal wall at fluoroscopy. The findings were subsequently
      confirmed by endoscopy and biopsy. RESULTS: Ectopic gastric mucosa in the upper
      esophagus was seen in 27 (25 men, two women) of the 1142 patients. Forty-three
      localized ectopic gastric mucosal patches varying in size from 5 mm to 32 mm were
      detected at the level of the thoracic inlet in the 27 patients. The most common
      radiographic finding was a pair of small indentations on the wall of the
      esophagus (18 patches). Other findings included a rimlike shadow (three patches),
      a pair of somewhat large indentations with a shallowly depressed area between
      them (two patches), one indentation (five patches), a small flat elevation (one
      patch), a serrated irregular outline (five radiologic lesions consisted of 11
      patches), other various irregular outlines (two patches), and a polypoid area
      (one patch). CONCLUSION: Prevalence of radiographic evidence of ectopic gastric
      mucosa in the upper esophagus is 2.4%. The lesion was found more commonly in men
      (3.1%) than in women (0.6%). Radiographic findings include a pair of indentations
      along the lateral margin of the esophagus and a rimlike shadow on the anterior or
      posterior wall. Recognition of the characteristic radiographic features of this
      abnormality makes endoscopy and follow-up unnecessary.

PMID- 7726046
TI  - CT diagnosis of acute appendicitis: imaging findings.
AB  - Acute appendicitis, at times, is a difficult clinical diagnosis. CT can play a
      valuable role in selected patients with suspected appendicitis; the CT diagnosis
      of acute appendicitis has high positive and negative predictive values, 96% and
      95%, respectively [1]. In this essay, we review the normal CT anatomy of the
      appendix and the right lower quadrant and illustrate the CT signs of appendicitis
      and important differential diagnostic entities. The CT appearance of
      complications of acute appendicitis is also presented, as are issues concerning
      examination technique and patient preparation.

PMID- 7726047
TI  - Echoplanar MR imaging for characterization of adrenal masses in patients with
      malignant neoplasms: preliminary evaluation of calculated T2 relaxation values.
AB  - OBJECTIVE: We undertook this study to assess the utility of echoplanar MR imaging
      for distinguishing benign from malignant adrenal masses in patients with known
      malignant neoplasms. MATERIALS AND METHODS: Thirty consecutive patients with 31
      adrenal masses and a known malignant neoplasm underwent breath-hold echoplanar MR
      imaging with a repetition time of 6000 msec and four echo times (40, 80, 120, 160
      msec) on a 1.5-T unit before biopsy. Subsequently, 10 masses were shown to be
      malignant at histologic examination, 12 masses were benign at histologic
      examination, and nine were thought to be benign because they had not changed in
      size at follow-up imaging. Mean lesion size was 2.4 +/- 2.1 cm. T2 calculations
      using regions of interest in the liver and adrenal mass were performed in each
      patient. RESULTS: The mean calculated T2 value of benign adrenal masses was 70.3
      msec (SD, 11.6 msec) versus 104.6 msec (SD, 35.2 msec) for malignant adrenal
      masses (p = .013). Using a cutoff T2 value of 84 msec, 19 (90%) of 21 benign
      masses and nine (90%) of 10 malignant masses were correctly classified. The mean
      adrenal/liver T2 ratio was 1.4 (SD, 0.25) for benign lesions, and 2.1 (SD, 0.78)
      for malignant lesions (p = .017). Using a cutoff ratio of 1.60, 19 (90%) of 21
      benign lesions and eight (80%) of 10 malignant lesions would have been correctly
      classified. CONCLUSION: This preliminary work suggests that obtaining T2
      calculations from echoplanar MR images of adrenal masses is a useful technique
      for distinguishing benign from malignant adrenal masses in patients at risk for
      adrenal metastasis.

PMID- 7726048
TI  - Abdominal aortic aneurysms: findings on three-dimensional display of helical CT
      data.
AB  - Excellent vascular opacification, reduction in misregistration artifacts, and the
      option of reconstructing overlapping scans from which three-dimensional (3D)
      models of the abdominal vessels may be rendered are among the benefits of helical
      CT [1-4]. The purpose of this essay is to illustrate the findings of 3D rendering
      of helical CT data in patients with abdominal aortic aneurysms.

PMID- 7726049
TI  - The normal prostate and periprostatic structures: correlation between MR images
      made with an endorectal coil and cadaveric microtome sections.
AB  - This pictorial essay illustrates the normal prostate and periprostatic structures
      seen on MR images obtained with an endorectal coil and correlates them with
      anatomic structures identified on serial microtome sections of a frozen human
      cadaver. The correlation shows that high-resolution MR imaging allows detailed
      visualization of normal anatomic structures. The ability to identify the normal
      anatomy and to recognize pathologic alterations provides valuable information
      concerning clinical decision making for both benign and malignant prostatic
      disease.

PMID- 7726050
TI  - Peritoneal carcinomatosis due to transitional cell carcinoma of the bladder: CT
      findings in two patients.

PMID- 7726051
TI  - Gas bubbles in the hip joint on CT: an indication of recent dislocation.
AB  - OBJECTIVE: The purpose of this study was to determine if gas bubbles in the hip
      joint seen on CT scans after trauma are reliable indicators of recent (< 48 hr)
      hip dislocation. We believe that the gas seen in the hip joint represents
      intracapsular nitrogen bubbles that result from the vacuum created by forcible
      distraction associated with traumatic dislocation. MATERIALS AND METHODS: CT
      scans of 79 consecutive patients with pelvic injury were reviewed
      retrospectively. We noted the number and position of intracapsular gas bubbles,
      presence of joint effusion, soft-tissue injury, and associated fractures or
      dislocations. Intracapsular gas bubbles were defined as round areas of low
      attenuation, in an intracapsular position, that on visual inspection were
      equivalent to air. Seventy-three of 79 patients were imaged within 48 hr of
      injury. Most patients had been involved in a motor vehicle collision or were
      pedestrians struck by a motor vehicle. Fifteen patients had hip dislocation,
      including one patient with bilateral dislocation. Fifty-five patients had pelvic
      fractures without hip dislocation, and nine patients had soft-tissue injury
      without fracture or dislocation. Fourteen of 16 dislocations had been reduced at
      the time of scanning. RESULTS: Gas bubbles were seen in the hip joint on CT scans
      in 13 (81%) of the 16 dislocated hips, including 12 (92%) of 13 dislocations in
      patients scanned within 4 hr of admission. Bubbles were present in 11 (79%) of 14
      hip joints that had dislocations reduced at the time of scanning and in both hip
      joints that remained dislocated. Most bubbles were located anterior to the
      femoral neck; however, bubbles were also seen posteriorly. Bubble size (1-3 mm)
      and number (1-7) varied. Only two (3%) of 64 patients without dislocation had
      intracapsular gas bubbles; one had been shot and the other had extensive soft
      tissue emphysema. CONCLUSION: In the absence of penetrating trauma, intracapsular
      gas bubbles on CT are reliable indicators of recent hip dislocation and may be
      the only objective finding of this injury.

PMID- 7726052
TI  - Normal bone marrow in the sacrum of young adults: differences between the sexes
      seen on chemical-shift MR imaging.
AB  - OBJECTIVE: Age-related changes in the distribution of fatty and nonfatty bone
      marrow in the pelvis and femur are well recognized. However, mapping not only of
      age-related MR appearance of normal bone marrow but also of potential variations
      in females versus males is necessary to differentiate normal findings from marrow
      disease. Accordingly, we studied possible sex-related differences in the MR
      imaging appearance of sacral bone marrow in young adults. SUBJECTS AND METHODS: A
      population of 21 healthy men and 21 healthy women (17-42 years old) was
      prospectively studied with chemical-shift pulse sequences. MR imaging (1.5 T) of
      the sacrum was done with frequency-selective fat images (SENEX [selective
      nonexcitation] 300/27) and water images (SENEX 1000/27) by using an elliptical
      surface coil. Two independent observers compared the signal intensity of sacral
      marrow with the signal of fatty tissue planes adjacent to the sacrum (fat images)
      and the signal of gluteus muscle (water images). T2 relaxation times were
      estimated by using a two-parametric monoexponential fit on SENEX 1000/27 and
      SENEX 1000/54 images. RESULTS: In both sexes, fat MR images showed a higher fat
      content and greater heterogeneity in the bone marrow of the lateral masses than
      in the vertebral bodies of the sacrum (p < .05). Yellow marrow in the lateral
      masses of the sacrum appeared brighter in men than in women (p < .05). The
      heterogeneity of fatty marrow did not differ significantly between the sexes. On
      water MR images, the signal intensity of the sacrum was higher in women (p <
      .05). T2 relaxation times were longer in nonfatty marrow with a high water signal
      intensity (41.8 +/- 5.5 msec versus 33.4 +/- 2.6 msec p < .01). CONCLUSION: Our
      findings show that the normal appearance of the sacral bone marrow depicted on
      chemical-shift MR imaging differs between young men and women. Awareness of these
      differences is important to avoid misinterpretation of normal MR findings seen in
      patients in this age group.

PMID- 7726053
TI  - MR diagnosis of labral tears of the shoulder: value of T2*-weighted gradient
      recalled echo images made in external rotation.
AB  - OBJECTIVE: Because several studies have shown that conventional MR imaging can
      fail to diagnose a significant percentage of labral tears, some authors have
      proposed obtaining T2*-weighted gradient-recalled echo images with the humerus in
      external rotation. The purpose of our study was to determine whether the
      diagnostic accuracy of detecting anteroinferior labral tears by MR imaging would
      be improved by adding a T2*-weighted gradient-recalled echo sequence with the
      humerus in external rotation. MATERIALS AND METHODS: The study included 24
      patients for whom axial MR images of the shoulder were obtained with the humerus
      in both the neutral position and external rotation. Two observers interpreted the
      images made in the neutral position and then noted any change in their
      interpretations after viewing findings on the external-rotation images. MR
      results were correlated with surgical findings. At surgery, 14 anteroinferior
      labra were found to be torn and 10 were found to be intact. RESULTS: Both
      observers identified one patient for whom a surgically proved labral tear was
      seen only on the external-rotation images. The sensitivity increased from 0.43 to
      0.50 (p = .35) for observer 1 and from 0.36 to 0.43 (p = .35) for observer 2. The
      specificity of 0.90 for both observers remained unchanged. The accuracy improved
      from 0.62 to 0.67 for observer 1 and from 0.55 to 0.62 for observer 2.
      CONCLUSION: The addition of external-rotation T2*-weighted gradient-recalled echo
      images to the MR examination for tears of the anteroinferior labrum leads to a
      small but statistically insignificant increase in diagnostic sensitivity. We
      conclude that the small increase in sensitivity does not justify the routine use
      of this sequence.

PMID- 7726054
TI  - Osteoid osteoma: percutaneous excision using a CT-guided coaxial technique.
AB  - OBJECTIVE: We describe a coaxial technique for percutaneous, CT-guided removal of
      osteoid osteoma in children. SUBJECTS AND METHODS: The study included eight
      children aged 3 years to 15 years 9 months who had signs and symptoms of osteoid
      osteoma. The diagnoses were confirmed by CT scans. Seven of nine lesions were
      removed manually with a coaxial technique and a trephine. Power tools were added
      to the technique in the other two cases. Removal of the nidus was confirmed by
      postprocedural CT scans and by histologic examination. RESULTS: All CT-guided
      excisions were technically successful, and only one minor complication occurred.
      One recurrence at 13 months was successfully treated percutaneously. CONCLUSION:
      CT-guided coaxial removal of osteoid osteoma is a safe and effective treatment.
      Increasing experience and the use of power tools in selected cases helps to
      shorten the procedure.

PMID- 7726055
TI  - Pleural hemorrhage in neonates on extracorporeal membrane oxygenation and after
      repair of congenital diaphragmatic hernia: imaging findings.
AB  - OBJECTIVE: The purpose of this study was to determine the frequency and range of
      radiographic and sonographic findings of clinically significant pleural
      hemorrhage in neonates who have had repair of a congenital diaphragmatic hernia
      and are being treated with extracorporeal membrane oxygenation (ECMO) for severe
      respiratory failure due to a combination of pulmonary hypoplasia and persistent
      pulmonary hypertension. Drainage and control of larger pleural hemorrhages and
      hemorrhagic pleural effusions, which may not be apparent clinically, can be
      essential to the successful completion of ECMO bypass support. MATERIALS AND
      METHODS: The medical records, chest radiographs, and thoracic sonograms of 32
      neonates with repaired congenital diaphragmatic hernia who were being treated
      with ECMO bypass were reviewed for radiographic and sonographic findings
      associated with significant pleural hemorrhage, defined as sufficient in amount
      to be recognizable by bedside imaging. Drainage of these hemorrhages was
      considered likely to result in improvement in the patient's clinical status and
      possibly to be essential to the patient's survival. The imaging findings most
      likely to reflect these large pleural hemorrhages were radiographic evidence of a
      rapid accumulation of pleural fluid or an atypical shift of mediastinal
      structures and sonographic demonstration of echogenic fluid in the pleural space.
      RESULTS: Nine patients had 11 episodes of pleural hemorrhage significant enough
      to produce recognizable radiographic and/or sonographic findings and to effect a
      change in clinical management. The imaging findings varied with the evolution of
      the usual thoracic changes after repair of the hernia, severity of pleural
      hemorrhage, and ability to drain the hemorrhage. Both tension and nontension
      hemothoraces and hemopneumothoraces were observed on portable chest radiographs
      before treatment. Atypical shift of mediastinal structures and/or rapid
      accumulation of pleural space fluid were the radiographic findings most
      suggestive of significant pleural hemorrhage and occurred in six of the nine
      patients. Sonography of the thorax confirmed pleural hemorrhage in eight patients
      and was nondiagnostic owing to overlying bandage material in one patient.
      CONCLUSION: The frequency of significant pleural hemorrhage in neonates with
      repaired congenital diaphragmatic hernia who were on ECMO bypass support was
      approximately 30%. The chest radiograph may be the initial indicator of large
      pleural hemorrhages in these patients. The radiographic findings can vary widely,
      from partial to complete opacification of the involved hemithorax and with
      varying degrees of contralateral mediastinal displacement. A shift in position of
      the ECMO cannulas may be the initial and only radiographic sign of pleural
      hemorrhage when both lungs are completely opaque and airless. Sonography is
      helpful in distinguishing hemothorax from pleural effusion. The combined
      radiographic and sonographic findings can be essential in deciding on appropriate
      therapeutic intervention.

PMID- 7726056
TI  - Detection of a poorly functioning malpositioned kidney with single ectopic ureter
      in girls with urinary dribbling: imaging evaluation in five patients.
AB  - OBJECTIVE: Some girls with lifelong continuous dribbling of urine despite
      successful toilet training have urographic or sonographic evidence of only one
      kidney. Such girls are likely to have a contralateral, poorly functioning,
      nonvisualized, malpositioned kidney with a nonduplicated collecting system and
      ureter draining through an ectopic orifice. Our objective was to analyze our
      experience with this group of patients to determine how best to confirm the
      presence and show the location of this abnormal kidney. MATERIALS AND METHODS: We
      reviewed the medical records and imaging studies of five such girls who were
      first seen at our hospital between 1975 and 1993 to determine how their poorly
      functioning, malpositioned kidney was detected. The imaging studies included
      sonography, excretory urography, vaginography, retrograde and intraoperative
      antegrade ureterography, renal cortical scintigraphy using 99mTc
      dimercaptosuccinic acid, CT, and MR imaging. RESULTS: All the abnormal kidneys
      were located on the left side. Excretory urography and sonography showed the
      abnormal kidney in only one of these five patients. In a second girl, retrograde
      ureterography showed the ureter of the dysplastic kidney after an ectopic
      ureteral orifice was discovered in the vagina during examination under general
      anesthesia. In a third, reflux from the vagina during a vaginogram showed the
      abnormal kidney. Renal cortical scintigraphy using dimercaptosuccinic acid showed
      the dysplastic, malpositioned, poorly functioning kidney in three girls. CT with
      special attention to the region of radionuclide uptake seen on scintigram showed
      the location of the dysplastic kidney more precisely in two patients. CONCLUSION:
      A girl with continuous dribbling of urine despite normal voiding habits whose
      excretory urogram and sonogram reveal only one kidney should have a
      dimercaptosuccinic-acid scintigram as the next imaging evaluation. A CT scan
      through the area of interest as determined by the dimercaptosuccinic-acid
      scintigram will more accurately localize the often ectopic kidney, thus
      facilitating its removal.

PMID- 7726057
TI  - Diagnosis of obstructive hydronephrosis in infants: comparison sonograms
      performed 6 days and 6 weeks after birth.
AB  - OBJECTIVE: The purpose of this study was to compare the usefulness of renal
      sonograms obtained 6 days and 6 weeks after birth in differentiating obstruction
      from nonobstruction in patients with antenatal pyelocaliceal dilatation shown by
      sonography and to establish sonographic criteria to determine the degree of
      postnatal pyelocaliceal dilatation that warrants further investigation. MATERIALS
      AND METHODS: Criteria for an infant to enter the study were fetal pyelectasis of
      4 mm or greater, two postnatal sonograms with the second showing persisting
      pyelectasis extending at least into the infundibula, and a voiding
      cystourethrogram showing normal findings. One hundred thirty kidneys in 100
      infants met the study criteria. The first postnatal sonogram was obtained at a
      mean age of 6 days (range, 1-14 days) and the second at a mean age of 6.6 weeks
      (range, 3-16 weeks). The degree of pyelectasis was measured in the
      anteroposterior direction on the transverse postnatal sonograms. The diagnosis of
      obstruction was made by excretory urography in 99 infants and nephrostography in
      one infant. Kidneys were categorized as definitely obstructed, possibly
      obstructed (anatomic features of obstruction on excretory urogram but
      functionally not obstructed), or not obstructed. Receiver-operating
      characteristic (ROC) curves based on renal pelvic diameters were plotted for both
      sonograms; the ability to detect definite obstruction or possible obstruction was
      compared for the two time periods; and optimal cutoff points were determined.
      RESULTS: The mean diameter of the renal pelvis was not significantly different
      between the sonogram obtained at 6 days and the sonogram obtained at 6 weeks for
      the 86 nonobstructed kidneys. For the 27 kidneys that were obstructed, the mean
      pelvic diameter increased from 18 mm (range, 5-54 mm) on the sonogram obtained at
      6 days to 22 mm (range, 11-60 mm) on the sonogram obtained at 6 weeks. The mean
      pelvic diameter of 17 kidneys categorized as possibly obstructed increased from 6
      mm (range, 0-11 mm) to 10 mm (range, 6-20 mm) between the first and second
      sonograms. The ROC curves for all sonograms obtained at 6 weeks provided cutoff
      points with greater sensitivity and specificity than did the curves for the
      sonograms obtained at 6 days. The optimal cutoff points were 6 mm for possible
      obstruction (sensitivity, 100%; specificity, 57%) and 11 mm for definite
      obstruction (sensitivity, 100%; specificity, 57%) and 11 mm for definite
      obstruction (sensitivity, 100%; specificity, 96%). CONCLUSION: Renal obstruction
      may be underestimated or missed on a renal sonogram obtained 6 days after birth.
      A sonogram obtained 6 weeks after birth is more specific for detecting
      obstruction.

PMID- 7726058
TI  - Infantile osteopetrosis complicated by rickets.

PMID- 7726059
TI  - Yolk sac tumor of the testis discovered on a routine annual sonogram in a boy
      with testicular microlithiasis.

PMID- 7726060
TI  - Anomalies of the fetal skeleton: sonographic findings.
AB  - Malformations of the fetal skeleton can be classified into two major categories.
      The generalized skeletal dysplasias are characterized by abnormalities in
      multiple bones throughout the fetus. In contrast, focal skeletal abnormalities
      manifest a variable pattern both in distribution and extent of involvement. This
      pictorial essay illustrates the primary sonographic findings that indicate the
      presence of a skeletal abnormality. The major and minor sonographic features that
      allow formation of a reasonable differential diagnosis are also considered.

PMID- 7726061
TI  - Cavernous sinus air following orbital trauma.

PMID- 7726062
TI  - Squamous cell carcinoma of the oral cavity: MR findings and value of T1-versus T2
      weighted fast spin-echo images.
AB  - OBJECTIVE: The purposes of this study were to describe the characteristics of
      squamous cell carcinomas of the oral cavity on unenhanced and contrast-enhanced
      T1-weighted spin-echo (SE) MR images and unenhanced T2-weighted fast spin-echo
      (FSE) MR images and to determine which sequences best delineate the margins and
      extent of the tumors. MATERIALS AND METHODS: Forty-four patients with proved
      squamous cell carcinoma of the oral cavity (tongue, 24; floor of mouth, seven;
      buccal mucosa, four; maxillary gingiva, two; and mandibular gingiva, seven)
      underwent unenhanced axial T2-weighted FSE MR imaging and unenhanced and enhanced
      axial and coronal T1-weighted SE MR imaging. The appearance, signal
      characteristics, and extent of the tumors were assessed, and the delineation of
      tumor margins with each sequence or combination of sequences was evaluated by use
      of a grading system ranging from 1 (poor) to 3 (excellent). Three patients were
      excluded because of artifacts on the MR images caused by dental restorations.
      RESULTS: Tumors in all 41 patients were depicted on unenhanced T1-weighted SE
      images, but in four patients, tumors were not visible on T2-weighted FSE images.
      Except for tumors that invaded the maxillary gingiva, the tumors generally had
      homogeneous, low signal intensity on unenhanced T1-weighted images and
      nonhomogeneous, high signal intensity on T2-weighted FSE images. All tumors
      showed enhancement, 76% with a nonhomogeneous appearance. The delineation of
      tumor margins was excellent (grade 3) in 31 cases and fair (grade 2) in 10 cases.
      The highest rating was given for unenhanced T1-weighted images in 10 cases, for
      contrast-enhanced T1-weighted images in 10 cases, for the combination of both
      unenhanced and contrast-enhanced T1-weighted images in 18 cases, for the
      combination of unenhanced T1-weighted and T2-weighted FSE images in five cases,
      and for T2-weighted FSE images in one case. In three cases, the highest rating
      was given for both combinations of pulse sequences. CONCLUSION: An unenhanced T1
      weighted sequence should be used as the basic pulse sequence for MR imaging of
      tumors of the oral cavity. When tumor margins are not clearly delineated with
      this sequence, T2-weighted FSE and contrast-enhanced T1-weighted sequences should
      be added. Although both of these sequences provide supplementary information, the
      contrast-enhanced T1-weighted sequence is more useful in delineating the margins
      and extent of tumors than is the T2-weighted FSE sequence.

PMID- 7726064
TI  - Helical CT with topical water-soluble contrast media for imaging of the lacrimal
      drainage apparatus.

PMID- 7726063
TI  - Imaging of the postoperative neck with emphasis on surgical flaps and their
      complications.
AB  - Radiologists are playing an increasingly important role in the management of
      patients with head and neck cancer. Imaging is often essential in preoperative
      planning. It is therefore imperative for the radiologist to be familiar with the
      wide variety of surgical procedures used as well as the normal CT and MR imaging
      appearance after such procedures. In addition, familiarity with the appearance of
      tumor recurrence and postoperative complications is essential. This pictorial
      essay illustrates the appearance of the normal and abnormal postoperative neck on
      CT scans and MR images, with an emphasis on reconstructive flaps. Postoperative
      complications evident on imaging studies are depicted, as is the appearance of
      tumor recurrence. One lymph node classification system is briefly reviewed as a
      basis for discussion of neck dissection and other surgical procedures.

PMID- 7726065
TI  - Short- and long-term hemodynamic effects of transjugular intrahepatic
      portosystemic shunts: a Doppler/manometric correlative study.
AB  - OBJECTIVE: The purposes of this study were to evaluate the effect of a well
      functioning transjugular intrahepatic portosystemic shunt (TIPS) on the
      splanchnic and intrahepatic circulation, to determine if sonographic measurements
      can predict shunt dysfunction before clinical manifestations of portal
      hypertension occur, and to compare Doppler sonographic findings with portocaval
      gradient measurements before and after shunt revision. SUBJECTS AND METHODS:
      Forty-four patients with cirrhosis (n = 43) and myelofibrosis (n = 1) who
      underwent successful TIPS insertion were included in this prospective study.
      Indications for TIPS placement were: refractory ascites (24 patients), bleeding
      esophageal varices (17 patients), portal hypertensive gastropathy (two patients),
      and bleeding colonic varices (one patient). The portal vein and the inferior vena
      cava were catheterized; and the portocaval gradient was recorded before TIPS
      placement, at 2 and 12 months after TIPS placement, and when clinical or Doppler
      findings suggested shunt dysfunction. Doppler studies were done within 1 week
      before TIPS placement, within 2 days after TIPS placement, every 2-3 months
      thereafter, and before and after a TIPS revision. The Doppler studies included
      flow volume measurements in the portal vein and in the stent, as well as
      determination of the direction of flow in the segmental branches of the portal
      vein, in the splanchnic veins, and in portosystemic collaterals. Changes in
      Doppler findings and in catheter pressure measurements were compared using
      Spearman's rank correlation test. Significance was set at the .05 level. RESULTS:
      A marked decrease (-51%) in portocaval gradient was observed after TIPS
      placement. At Doppler sonography, portal vein velocity and diameter were both
      higher after TIPS placement, resulting in a marked increase in portal venous flow
      (170%). Mean flow velocity in the shunt was 55.8 +/- 3.6 cm/sec, and flow volumes
      in the shunt and in the main portal vein were 1596 ml/min and 1731 ml/min,
      respectively (p = nonsignificant). Dysfunction of the stent occurred in 27% of
      the patients. Changes in stent blood flow volume were closely related to changes
      in the portocaval gradient (r = -0.67, p < .001). Reduction of blood flow volume
      in the stent or change of direction of flow in intrahepatic portal veins or in
      collateral veins signaled shunt dysfunction (84% sensitivity, 89% specificity).
      CONCLUSION: Marked hemodynamic changes in the portal venous system occur soon
      after a TIPS procedure. Monitoring of shunt function with periodic Doppler
      sonography, including calculation of shunt blood flow, is useful in detecting
      shunt dysfunction before clinical signs occur.

PMID- 7726066
TI  - Lysolecithin-induced demyelination in primates: preliminary in vivo study with MR
      and magnetization transfer.
AB  - PURPOSE: To study bystander demyelination in multiple sclerosis with an
      experimental in vivo model of toxic demyelination. METHODS: Toxic demyelinating
      lesions were created in two monkeys by injection of lysophosphatidylcholine in
      the centrum semiovale. Follow-up was done clinically and with serial MR studies,
      including T2-weighted and gadolinium-enhanced T1-weighted images and measurement
      of magnetization transfer ratio, until the animals were killed at days 14 and 34,
      respectively. Light and electron microscopy analysis was compared with MR data.
      RESULTS: Interval measurement of magnetization transfer ratio during the course
      of the experiment revealed a maximum decrease at day 7 to day 8, associated with
      the greatest clinical manifestations. The lowest values of magnetization transfer
      ratio correlated with histopathologic findings of myelin and axon destruction.
      Magnetization transfer ratio measurements appear to be sensitive to
      macromolecular destruction and specifically to membrane disorganization. At no
      time was gadolinium enhancement observed in this model of toxic demyelination.
      CONCLUSION: Preliminary results of this study indicated that magnetization
      transfer is a good technique to follow in vivo matrix destruction in brain
      parenchyma lesions. The results suggest also that phases of toxic demyelination
      in multiple sclerosis might not show gadolinium enhancement. Differentiation
      between demyelinating activity and associated inflammation in multiple sclerosis
      lesions should be considered in further in vivo work.

PMID- 7726067
TI  - MELAS syndrome: imaging and proton MR spectroscopic findings.
AB  - PURPOSE: To evaluate imaging findings in MELAS (mitochondrial myopathy,
      encephalopathy, lactic acidosis, strokes) syndrome for the presence and location
      of infarctions and the presence of lactate. METHODS: Eight patients were studied
      with MR (n = 8) and CT (n = 2). One patient underwent single-photon emission CT
      with technetium 99m hexamethyl-propyleneamine oxime and one patient had
      conventional catheter angiography. One fixed brain was studied with MR imaging.
      Five patients underwent single volume proton MR spectroscopy. Imaging studies
      were evaluated for atrophy, edema, and infarctions. Proton MR spectroscopy was
      visually analyzed for presence or absence of lactate. RESULTS: One patient showed
      a cerebral infarction, and later a second distant infarction developed. One
      patient showed a transient area of cortical edema. Two patients had small
      nonspecific periventricular white matter abnormalities and one patient had
      diffuse white matter hyperintensities. Two patients had nonspecific MR
      abnormalities (probably age-related changes), and two had normal MR findings.
      None had basal ganglia involvement. Proton MR spectroscopy showed presence of
      lactate in one case with transient cortical edema; in two cases with nonspecific
      (probably age-related) brain findings; and in two patients with normal MR
      findings. CONCLUSIONS: Patients with MELAS have a variety of MR findings. The
      fact that proton MR spectroscopy showed lactate in all five cases studied,
      regardless of MR findings, indicates that proton MR spectroscopy may be more
      sensitive in the detection of MELAS-associated abnormalities than MR imaging.

PMID- 7726069
TI  - Magnetization transfer imaging of periventricular hyperintense white matter in
      the elderly.
AB  - PURPOSE: To characterize with magnetization transfer imaging the pathologic
      substrate of the nonspecific periventricular hyperintense white matter changes
      seen on T2-weighted images of elderly patients. METHODS: Twenty-one elderly
      patients with periventricular hyperintense white matter on T2-weighted MR images
      and eleven control subjects were studied using MT technique. Magnetization
      transfer ratios (MTRs) were calculated for the periventricular hyperintense white
      matter and normal-appearing white matter. These MTRs were correlated with
      histopathologic changes that have previously been reported as well as with
      established MTRs for other lesions. RESULTS: The MTRs (mean, 35.2; SD, 1.2) in
      the periventricular hyperintense white matter are lower than those in the normal
      white matter of the patient (mean, 40.8; SD, 1.4) and control (mean, 41.3; SD,
      1.8) groups. These MTRs are much higher than those of demyelinating lesions but
      are similar to those of experimental lesions with just edema. CONCLUSION: Because
      MTR may reflect to some extent histopathologic changes and thus provide more
      specificity than conventional pulse sequences, the main pathologic substrate
      accounting for the lower MTR in periventricular hyperintense white matter is
      probably the increased water content in reactive astrocytes.

PMID- 7726068
TI  - Quantitative volumetric analysis of brain MR: normative database spanning 5
      decades of life.
AB  - PURPOSE: To present a normative volumetric database, spanning 5 decades of life,
      of cerebrospinal fluid, subarachnoid cerebrospinal fluid, total brain volume,
      total ventricular volume (component ventricular volumes of lateral, temporal
      horn, and third and fourth ventricles) and estimates of white and gray matter,
      based on a multispectral segmentation of brain MR. This database is presented as
      a reference for future studies comparing pathologic states. METHOD: One hundred
      ninety-four healthy subjects, ranging in age from 16 to 65 years, received
      standard axial intermediate- and T2-weighted spin-echo MR images. Multispectral
      segmentation and volume analysis were performed using ANALYZE. RESULTS: Normative
      volumetric estimates, both uncorrected and corrected for differences in total
      intracranial volume, were obtained for all subjects and presented by decade and
      sex. Age-related cerebrospinal fluid changes were evident for both male and
      female subjects. Most gender differences were eliminated by correction for
      differences in total intracranial volume. Standard and fast spin-echo acquisition
      methods gave comparable volume estimates. Total brain volume measurements from MR
      compare favorably with data from large autopsy series. CONCLUSION: Although there
      may be limitations to generalizations, these normative data tables can provide a
      comparison index for contrasting pathologic groups with a normative sample.

PMID- 7726070
TI  - The effect of gadolinium on the sensitivity and specificity of MR in the initial
      diagnosis of multiple sclerosis.
AB  - PURPOSE: To determine whether gadolinium can improve the sensitivity and
      specificity of MR imaging for the initial diagnosis of multiple sclerosis.
      METHODS: Patients (n = 57) with neurologic symptoms suggesting multiple sclerosis
      were studied prospectively. MR imaging consisted of T2-weighted and gadolinium
      enhanced T1-weighted spin-echo images. Lumbar puncture was performed for
      cerebrospinal fluid analysis in 34 patients. RESULTS: After imaging, 17 patients
      (35%) had clinically definite multiple sclerosis. Cerebrospinal fluid examination
      had a sensitivity of 69% and specificity of 38%. Using liberal criteria, the
      sensitivity of T2-weighted MR imaging was 94% and the specificity 55%; using more
      strict criteria, the specificity increased to 65% with a sensitivity of 88%.
      Gadopentetate dimeglumine enhancement increased the specificity further to 80%
      with a loss of sensitivity (59%). CONCLUSION: Gadolinium enhancement increases
      the specificity of MR imaging in the early diagnosis of multiple sclerosis.

PMID- 7726071
TI  - Contrast enhancement in spinal nerve roots: an experimental study.
AB  - PURPOSE: To examine histopathologically the endothelium of contrast-enhancing
      spinal nerve roots. METHODS: In five adult baboons, chronic compression of the
      left S-1 spinal nerve root sufficient to produce a change in the evoked potential
      was produced by means of a suture tied around the nerve. The animals were studied
      with MR at 8 and 16 days after nerve compression and then killed for
      histopathologic and electron microscopic studies. Histopathologic changes in the
      nerve roots demonstrating contrast enhancement were described. RESULTS: In all
      compressed spinal nerves, contrast enhancement was observed. Histopathologically,
      wallerian degeneration of the root and inflammation and disruption of the
      endothelium of capillaries in the spinal nerve were evident. CONCLUSIONS:
      Degenerative changes in the nerve root and the capillary endothelium of a lumbar
      spinal nerve are associated with contrast enhancement.

PMID- 7726072
TI  - Contrast-enhanced radicular veins on MR of the lumbar spine in an asymptomatic
      study group.
AB  - PURPOSE: To determine whether radicular enhancement occurs in asymptomatic
      persons and, if so, to provide insight into the mechanism of such enhancement.
      METHODS: Thirty asymptomatic volunteers were studied with gadolinium-enhanced MR
      (0.1 mmol/kg) of the lumbar spine. The precontrast axial T1-weighted sequences
      were reviewed for the entry section phenomenon of flow-related enhancement. If
      present, the sequence was repeated in combination with a superior saturation
      pulse in an attempt to eliminate this phenomenon. All studies were reviewed to
      document the incidence of radicular enhancement and determine its association
      with the entry section phenomenon. RESULTS: The entry section phenomenon was
      observed in 16 of 30 volunteers with successful elimination obtained in all
      cases. Eighteen of the volunteers demonstrated radicular enhancement; 16 of the
      18 enhancing roots were associated with the entry section phenomenon.
      CONCLUSIONS: Radicular enhancement occurs commonly in asymptomatic volunteers.
      This phenomenon most likely represents the enhancement of prominent radicular
      veins. We urge caution in interpreting this finding as abnormal in the
      symptomatic population with degenerative disk disease.

PMID- 7726073
TI  - MR of omental myelosynangiosis.
AB  - PURPOSE: To describe MR findings in patients who have undergone omental
      transposition (omental myelosynangiosis) for spinal cord revascularization.
      METHODS: Spin-echo MR images, without and with intravenous gadolinium, were
      obtained before and after surgery in three patients using a quadrature spine
      coil. Three-dimensional time-of-flight spinal MR angiography was also performed.
      RESULTS: On routine MR, the transposed omentum is an irregular, lobulated fat
      equivalent mass, containing serpiginous areas of flow void, which extends through
      the laminectomy site to lie directly adjacent to the cord surface. MR angiography
      demonstrated small omental vessels, some coursing to the omentum-cord interface;
      however, no definite extension into the cord was detected. In all patients, there
      was alteration in cord size and contour after transposition, but no change in
      cord signal. Clinical improvement was observed in one of the three patients. The
      signal characteristics of the transposed omentum changed, showing less
      homogeneity and a gradual loss of the signal over a period of 4 months.
      CONCLUSIONS: MR delineates transposed omentum and associated postoperative
      changes in omental myelosynangiosis. MR angiography is useful as an adjunct to
      demonstrate the small vessels near the omentum-cord interface, but lacks
      sufficient resolution to demonstrate neoangiogenesis within the cord.

PMID- 7726074
TI  - MR evaluation of vertebral metastases: T1-weighted, short-inversion-time
      inversion recovery, fast spin-echo, and inversion-recovery fast spin-echo
      sequences.
AB  - PURPOSE: To compare the detectability of vertebral metastatic disease on T1
      weighted, short-inversion-time inversion recovery (STIR), fast spin-echo (FSE),
      fat-saturated FSE, and inversion recovery FSE (IRFSE) MR sequences using percent
      contrast and contrast-to-noise ratios. METHODS: Patients with proved metastatic
      disease underwent imaging on a 1.5-T MR system with sagittal T1-weighted
      (800/20/2 [repetition time/echo time/excitations]) (91 patients), STIR
      (1400/43/2; inversion time, 140) (91 patients), FSE (4000/180/2) (46 patients),
      fat-saturated FSE (4000/180/2) (16 patients), and IRFSE (29 patients) sequences.
      Percent contrast and contrast-to-noise ratio were calculated for the lesions. The
      number of metastatic lesions detected with each of the pulse sequences was also
      calculated. RESULTS: Mean percent contrast was, for T1-weighted sequence, -42.2
      +/- 1%; STIR, 262 +/- 34%; FSE, 121 +/- 21%; fat-saturated FSE, 182 +/- 6%; and
      IRFSE, 272 +/- 47%. The mean contrast-to-noise ratio for T1-weighted was -4.63 +/
      1.7; STIR, 10.8 +/- .98; FSE, 4.16 +/- .76; fat-saturated FSE, 4.87 +/- .19; and
      IRFSE, 5.2 +/- .87. STIR and IRFSE showed the highest number of lesions, followed
      by T1-weighted, fat-saturated FSE, and FSE sequences. T1-weighted sequences
      showed 94%, FSE 55%, and fat-saturated FSE 78% of the lesions detected. Epidural
      metastatic lesions were better depicted on T1-weighted, FSE, and fat-saturated
      FSE sequences. CONCLUSION: STIR was superior to both T1-weighted and FSE (with
      and without fat saturation) for detection of metastatic lesions, in terms of both
      percent contrast and contrast-to-noise ratio and visibility. IRFSE was equal to
      STIR for the detection of metastasis by both subjective and objective criteria.
      T1-weighted, FSE, and fat-saturated FSE sequences were superior to STIR and IRFSE
      in the detection of epidural metastatic disease. IRFSE provided faster scanning
      time, which could be translated into greater resolution.

PMID- 7726075
TI  - MR angiography of spinal vascular malformations.
AB  - PURPOSE: To determine the potential and limitations of MR angiography in the
      evaluation of spinal vascular malformations. METHODS: Eleven consecutive patients
      with spinal vascular malformations proved with spinal selective arteriography
      underwent two-dimensional phase-contrast MR angiography. RESULTS: Abnormal
      vessels within the spinal canal were identified with MR angiography in 10
      patients. In 1 patient with a dural arteriovenous fistula no definite vascular
      abnormality was seen with MR angiography. Correlation of MR angiography with
      spinal selective arteriography showed that the former allowed identification of
      the arterial feeder in 3 patients with intramedullary arteriovenous malformations
      and 2 with perimedullary arteriovenous fistula, whereas the source of intradural
      draining vein was seen in only 2 of 6 patients with dural arteriovenous fistula.
      CONCLUSION: MR angiography is a promising complementary tool to MR imaging for
      detection and characterization of spinal vascular malformations.

PMID- 7726076
TI  - The efficacy of particulate embolization combined with stereotactic radiosurgery
      for treatment of large arteriovenous malformations of the brain.
AB  - PURPOSE: To evaluate the efficacy of combined particulate embolization and single
      stage stereotactic radiosurgery in the treatment of large arteriovenous
      malformations (AVMs) of the brain. METHODS: Twenty-four patients with large brain
      AVMs (diameter > 3.0 cm; volume > 14 cm3), who had previously undergone
      particulate embolization and stereotactic radiosurgery, were retrospectively
      evaluated 2 or more years after radiosurgery. RESULTS: In 12 (50%) of these
      patients there was complete AVM obliteration, comparing favorably with a 58%
      obliteration rate in a group of AVMs having a 4- to 10-cm3 volume, treated by
      radiosurgery alone. Recanalization of embolized, but not radiated, AVM segments
      was identified in 3 (12%) patients. However, long-term occlusion was demonstrated
      in the embolized portions of most AVMs subsequently treated by radiosurgery.
      Complications included 1 (4%) patient with a mild upper extremity paresis after
      radiosurgery and 2 (8%) patients with transient neurologic deficits after
      embolization. CONCLUSION: Combined embolization and stereotactic radiosurgery was
      more efficacious than radiosurgery alone for large brain AVMs. Recanalization
      after embolization did occur but was a relatively minor cause of treatment
      failure.

PMID- 7726077
TI  - Intraoperative digital subtraction angiography: a review of 112 consecutive
      examinations.
AB  - PURPOSE: To examine the effect of intraoperative angiography on neurosurgery and
      angiographic technical success, safety, and accuracy. METHODS: Angiographic
      studies, surgical reports, and hospital records were reviewed retrospectively for
      112 consecutive procedures in which intraoperative angiography was performed
      during neurosurgery. The results of conventional postoperative angiograms in 28
      of the 112 procedures were also reviewed. A portable digital subtraction
      angiography unit was used for all patients. Decisions in the operating room were
      based on review of stored videotaped images. RESULTS: Eighteen studies were
      obtained in 14 patients after arteriovenous malformation resection. Unsuspected
      residual nidus was identified and resected in 3 patients. The intraoperative
      angiogram also altered therapy for 2 patients undergoing staged resections of
      arteriovenous malformations. Sixty-six studies were performed after aneurysm
      clipping, with clinically significant changes in surgical therapy made in 5
      patients. Of 28 examinations after carotid endarterectomy, 3 led to revision. Two
      complications of angiography occurred. One led to a permanent neurologic deficit,
      yielding a complication rate of 1.5% for stroke. Two examinations could not be
      completed because of technical factors. Two false-negative examinations were
      identified on postoperative studies. One patient with a normal intraoperative
      study after carotid endarterectomy thrombosed the repaired internal carotid
      artery after surgery. CONCLUSIONS: Intraoperative angiography altered surgery in
      13 of 112 procedures on 104 patients. This study supports the use of
      intraoperative angiography in arteriovenous malformation resection and in complex
      aneurysm surgery, but not for routine carotid endarterectomy.

PMID- 7726079
TI  - Embolization of dural arteriovenous fistulas with interlocking detachable coils.
AB  - Our clinical experience with interlocking detachable coils for the embolization
      of high-flow dural arteriovenous fistulas is reported. Interlocking detachable
      coils are useful for transarterial and transvenous embolizations of dural
      arteriovenous fistulas because (a) immediate coil detachment is possible, (b) the
      coils can be replaced easily, (c) detached coils rarely migrate, and (d) fewer
      interlocking detachable coils than conventional fiber coils are required for
      successful embolization.

PMID- 7726078
TI  - Treatment of traumatic arterial vasospasm with intraarterial papaverine infusion.
AB  - We report a case of severe posttraumatic arterial vasospasm treated with
      repetitive intraarterial papaverine infusions. The salient features of the
      mechanism of action of papaverine are included.

PMID- 7726080
TI  - High-flow, small-hole arteriovenous fistulas: treatment with electrodetachable
      coils.
AB  - We present one case of carotid-cavernous fistula caused by percutaneous treatment
      of trigeminal neuralgia and one case of vertebrovertebral fistula caused by
      percutaneous internal jugular vein cannulation. Each fistula had a small
      arteriovenous communication that prevented the use of detachable balloons.
      Endovascular transarterial treatment of these two iatrogenic fistulas with
      electrically detachable platinum coils was performed. Both fistulas were occluded
      with preservation of the parent artery, and the patients have fully recovered.

PMID- 7726081
TI  - Aneurysm formation after carotid occlusion.
AB  - We present two cases of subarachnoid hemorrhage caused by aneurysm development
      and enlargement in the anterior communicating artery complex. The cases occurred
      in a series of 58 balloon occlusions for unclippable giant aneurysms of the
      internal carotid artery.

PMID- 7726082
TI  - Cystic expansile masses of the maxilla: differential diagnosis with CT and MR.
AB  - PURPOSE: To describe the CT and MR findings of various entities causing cystic
      expansile masses in the maxilla and the significance of the cortical bony plate
      between the lesions and sinus cavities in the differential diagnosis. METHODS: CT
      findings of 28 patients with cystic expansile masses of the maxilla, including 20
      cases of maxillary mucoceles (17 postoperative mucoceles, 2 mucoceles of a
      septated compartment of the maxillary sinuses, and 1 maxillary antral mucocele
      with inflammatory ostial obstruction), 3 cases of fissural cyst, 4 cases of
      odontogenic cyst, and 1 case of maxillary cystic ameloblastoma, were reviewed.
      Six cases (4 postoperative mucoceles and 2 odontogenic cysts) were also examined
      with MR. RESULTS: A thin bony plate between the lesion and antral cavity was
      demonstrated in every extraantral lesion (ameloblastoma, fissural cysts, and
      odontogenic cysts) and distinguishing these abnormalities from the antral lesions
      (mucoceles). All mucoceles showed findings of antral lesions except 2 cases of
      mucoceles at the septated compartments of the sinuses, in which thin bony septa
      were identified between the lesions and remaining sinus cavities. Postoperative
      mucoceles showed hyperostotic and retracted bony walls caused by previous surgery
      and localized erosion of bony walls with localized bulging of the cystic masses
      in every case. CONCLUSION: In the differential diagnosis of cystic masses of the
      maxilla, careful identification of the bony walls of the antrum and bony septa
      may allow one to locate the origin of a mass as antral or extraantral. This is
      important to an appropriate differential diagnosis.

PMID- 7726083
TI  - MR in partial epilepsy: value of high-resolution volumetric techniques.
AB  - PURPOSE: To assess the utility of high-resolution volumetric MR examinations with
      thin partition size for patients with simple partial epilepsies that were well
      located with electrical and clinical criteria. METHODS: Fifteen patients with
      normal standard MR findings were studied with three-dimensional Fourier transform
      volumetric MR examinations using thin (1 to 1.5 mm) partition size. Imaging was
      done in the coronal plane, then reformatted manually on an independent console
      with each gyrus analyzed in the planes parallel and perpendicular to its axis.
      RESULTS: Cortical abnormalities were detected in 8 of the 15 patients in the
      study. Surgical resection of the affected cortex in 2 patients showed
      polymicrogyria in one and dysplastic cortical organization in the other.
      CONCLUSION: In this preliminary study, 3-D Fourier transform volumetric MR
      examinations with thin partition size appeared to be useful in identifying
      cortical dysplasias in patients with localized simple partial epilepsies.

PMID- 7726084
TI  - Epilepsy associated with cerebral arteriovenous malformations: a multivariate
      analysis of angioarchitectural characteristics.
AB  - PURPOSE: To identify the morphological vascular characteristics of cerebral
      arteriovenous malformations (AVMs) that predict a clinical presentation of
      epilepsy. METHOD: Fifteen angioarchitectural characteristics of brain AVMs were
      selected for assessment in 100 consecutive patients referred to our institution
      for endovascular treatment. In this population, 47% of the AVMs were diagnosed as
      a consequence of epilepsy. The angioarchitectural characteristics and population
      demographics were statistically analyzed by means of multivariate analysis.
      RESULTS: The following six parameters were found to be the most predictive of
      epilepsy: cortical location of the AVM, feeding by the middle cerebral artery,
      cortical location of the feeder, absence of aneurysms, presence of varix/varices
      in the venous drainage, and association of varix and absence of intranidal
      aneurysms. Three factors were not among the most predictive factors of epilepsy
      but were significantly associated with the onset of seizures: AVM feeding by the
      external carotid artery, a temporal cortical location, and a parietal cortical
      location. CONCLUSION: Detailed analysis of the angioarchitecture of intracranial
      AVMs has helped us identify features that strongly correlate with epilepsy. This
      may aid in future understanding of the physiopathologic mechanisms in epilepsy
      associated with AVMs, and in identifying goals of treatment for epileptogenic
      AVMs.

PMID- 7726085
TI  - The Stockholm School of Neuroradiology.

PMID- 7726086
TI  - In vivo MR determination of water diffusion coefficients and diffusion
      anisotropy: correlation with structural alteration in gliomas of the cerebral
      hemispheres.
AB  - PURPOSE: To determine whether a relationship exists between water diffusion
      coefficients or diffusion anisotropy and MR-defined regions of normal or abnormal
      brain parenchyma in patients with cerebral gliomas. METHODS: In 40 patients with
      cerebral gliomas, diffusion was characterized in a single column of interest
      using a motion-insensitive spin-echo sequence that was applied sequentially at
      two gradient strength settings in three orthogonal directions. Apparent diffusion
      coefficients (ADCs) were derived for the three orthogonal axes at 128 points
      along the column. An average ADC and an index of diffusion anisotropy (IDA =
      diffusion coefficientmax-min/diffusionmean) was than calculated for any of nine
      MR-determined regions of interest within the tumor or adjacent parenchyma.
      RESULTS: In cerebral edema, mean ADC (all ADCs as 10(-7) cm2/s) was 138 +/- 24
      (versus 83 +/- 6 for normal white matter) with mean IDA of 0.26 +/- 0.14 (versus
      0.45 +/- 0.17 for normal white matter). Solid enhancing central tumor mean ADC
      was 131 +/- 25 with mean IDA of 0.15 +/- 0.10. Solid enhancing tumor margin mean
      ADC was 131 +/- 25, with IDA of 0.25 +/- 0.20. Cyst or necrosis mean ADC was 235
      +/- 35 with IDA of 0.07 +/- 0.04. CONCLUSION: In cerebral gliomas ADC and IDA
      determinations provide information not available from routine MR imaging. ADC and
      IDA determinations allow distinction between normal white matter, areas of
      necrosis or cyst formation, regions of edema, and solid enhancing tumor. ADCs can
      be quickly and reliably characterized within a motion-insensitive column of
      interest with standard MR hardware.

PMID- 7726087
TI  - The effect of contrast dose, imaging time, and lesion size in the MR detection of
      intracerebral metastasis.
AB  - PURPOSE: To evaluate the effect of MR contrast dose versus delayed imaging time
      on the detection of metastatic brain lesions based on lesion size. METHODS:
      Contrast MR examinations with gadoteridol were obtained in 45 patients with brain
      metastases. The patients were divided into two groups: 16 received cumulative
      standard dose (0.1 mmol/kg) and 29 received cumulative triple dose (0.3 mmol/kg).
      Both groups were evaluated at two dose levels (lower dose and higher dose) with
      two separate injections. Each patient received an initial bolus injection of
      either 0.05 (cumulative standard dose) or 0.1 (cumulative triple dose) mmol/kg of
      gadoteridol to reach the lower-dose level and underwent imaging immediately and
      10 and 20 minutes later. Thirty minutes after injection, an additional bolus
      injection of 0.05 (cumulative standard dose) or 0.2 (cumulative triple dose)
      mmol/kg was administered to reach the cumulative higher-dose level (cumulative
      standard dose, 0.1 mmol/kg; cumulative triple dose, 0.3 mmol). Images were
      acquired immediately. RESULTS: There was no difference in the detection rate for
      lesions larger than 10 mm among T2-weighted, lower-dose immediate and delayed, or
      immediate higher-dose images in both study groups. Lesions smaller than 10 mm had
      improved detection with delayed imaging in both study groups; however, the
      immediate higher-dose studies still had the highest detection rate. CONCLUSION:
      In the evaluation of small central nervous system metastases, either delayed
      imaging after the injection of standard contrast dose or higher contrast dose may
      improve their detection, and therefore affect clinical management. Higher
      contrast dose (cumulative triple dose) studies appear to be more effective than
      delayed imaging with standard dose.

PMID- 7726088
TI  - Increased brain water self-diffusion in patients with idiopathic intracranial
      hypertension.
AB  - PURPOSE: To investigate changes in brain water diffusion in patients with
      idiopathic intracranial hypertension. METHODS: A motion-compensated MR pulse
      sequence was used to create diffusion maps of the apparent diffusion coefficient
      (ADC) in 12 patients fulfilling conventional diagnostic criteria for idiopathic
      intracranial hypertension and in 12 healthy volunteers. RESULTS: A significantly
      larger ADC was found within subcortical white matter in the patient group (mean,
      1.16 x 10(-9) m2/s) than in the control group (mean, 0.75 x 10(-9) m2/s), whereas
      no significant differences were found within cortical gray matter, the basal
      nuclei, the internal capsule, or the corpus callosum. Four of 7 patients with
      increased ADC in subcortical white matter also had increased ADC within gray
      matter. CONCLUSION: Measurement of diffusion coefficients in vivo demonstrated
      increased local water mobility within subcortical white matter in 7 patients with
      idiopathic intracranial hypertension that otherwise appeared normal on
      conventional MR imaging. Further studies are necessary to assess the clinical
      significance of these observations.

PMID- 7726089
TI  - Analysis of cerebrospinal fluid flow waveforms with gated phase-contrast MR
      velocity measurements.
AB  - PURPOSE: To analyze the characteristics of normal cerebrospinal fluid (CSF) flow
      waveforms and to relate them to the arterial input and venous output flow
      waveforms in healthy volunteers. METHODS: Cine phase-contrast MR was obtained in
      17 volunteers. The temporal velocity information from the cervical pericord CSF
      spaces, basal cisterns, and aqueduct, as well as the internal carotid and
      vertebral arteries and internal jugular veins, were plotted as waveforms. The
      waveforms were analyzed for configurations, amplitudes, and temporal patterns. In
      four volunteers the reproducibility of the precord CSF flow waveforms was
      examined on different days. In three volunteers the effect of jugular venous
      compression on the precord and aqueductal CSF flow waveforms was also evaluated.
      RESULTS: (a) Distinct and reproducible configurational features were observed in
      the CSF flow waveforms. Jugular venous compression produced elevation of the
      disatolic slope of the precord waveforms. (b) The amplitudes were variable.
      Jugular venous compression reduced the precord CSF velocities. (c) The systolic
      temporal parameters were less variable and more reproducible than the diastolic
      temporal parameters. Jugular venous compression resulted in delay in the systolic
      parameters of the precord waveforms. (d) Craniocaudal and caudocranial postcord
      CSF flow occurred either simultaneous with or earlier than the precord CSF flow.
      Pericord CSF flow in either direction preceded that in the cisterns and in the
      aqueduct. (e) A significant temporal relationship was noted in the precord space
      between the time of the R wave to the maximum velocities and the arterial flow.
      CONCLUSION: CSF flow waveform analysis seems to be a reliable, reproducible, and
      sensitive method for assessing the CSF dynamics.

PMID- 7726090
TI  - Essential hypertension and neurovascular compression at the ventrolateral medulla
      oblongata: MR evaluation.
AB  - PURPOSE: To investigate, using MR imaging, neurovascular compression at the
      ventrolateral medulla oblongata in patients with essential hypertension. METHODS:
      Thirty-two patients with essential hypertension (57.6 +/- 7 years of age), 6
      patients with secondary hypertension (56.7 +/- 10.3 years of age), and 18 control
      subjects (50.5 +/- 11 years of age) were evaluated. Transaxial three-dimensional
      fast low angle shot images were obtained (38/6/1 [repetition time/echo
      time/excitations]). The center of a 40-mm-thick slab (16 partitions) was placed
      at the pontomedullary junction. We evaluated the relationships between the upper
      ventrolateral medulla and the vertebral arteries and branches identified by their
      flow-related hyperintensities in each group. RESULTS: In the essential
      hypertension group, 29 (90.6%) of 32 cases showed neurovascular compression. Of
      those, 22 demonstrated neurovascular compression on the left side, 3 on both
      sides, and 4 on the right side. In the control group, 4 cases of 18 showed
      neurovascular compression. In the secondary hypertension group, 1 of 6 cases
      showed neurovascular compression. The rates of observed neurovascular compression
      between controls and essential hypertension group were statistically significant.
      CONCLUSION: We found a close correlation between essential hypertension and
      neurovascular compression at the ventrolateral medulla oblongata on the left
      side. MR with a 3-D fast low-angle shot sequence has acceptable spatial
      resolution and depicts blood vessels simultaneously by flow-related phenomena.

PMID- 7726091
TI  - Automated MR segmentation method clarified.

PMID- 7726092
TI  - In vivo MR study of brain maturation in normal fetuses.
AB  - PURPOSE: To illustrate normal maturation of the fetal brain, including the
      migrational layer, gray matter, early myelination of internal capsules, optic
      radiations, and corona radiata. METHODS: Seventy-seven fetal brains, ranging from
      21 to 38 weeks of gestational age, were examined with MR in vivo; 33 were
      considered normal. MR examinations were performed as T1-weighted sequences in the
      axial, sagittal, and coronal planes. The neuropathologic examination (four cases)
      and clinical and/or neuroradiologic examinations confirmed the antenatal data.
      RESULTS: From 21 to 25 weeks, the cerebral ventricles are large, corresponding to
      the relative fetal hydrocephalus. A slight high signal intensity can be observed
      in the basal ganglia as early as 21 weeks. In the cerebral hemispheres, a
      multilayered pattern that can be observed from 23 to 28 weeks includes the
      cortical ribbon, the germinal matrix, and an intermediate layer corresponding to
      the migrating glial cells. These findings are probably related to areas of
      increased cellularity. A high signal intensity can be seen within the dorsal part
      of the brain stem as early as 23 weeks, within the posterior limb of the internal
      capsules at 31 weeks, and within the central area of the cerebral hemispheres at
      35 weeks. Those patterns are probably caused by the evolving process of
      myelination. CONCLUSIONS: MR allows depiction of signal changes corresponding
      either to an increase in cellularity or to the evolving processes of myelination,
      depending on the stage of the pregnancy.

PMID- 7726093
TI  - MR of benign chondroblastoma of the temporal bone.
AB  - A benign chondroblastoma of the temporal bone in an 8-year-old boy is reported.
      Head CT showed an expansile mass with calcifications in the center. The tumor
      appeared as a well-lobulated, hypointense intraosseous mass on T1-weighted brain
      MR; it was isointense to brain parenchyma on intermediate-weighted images and
      enhanced homogenously with gadolinium.

PMID- 7726094
TI  - Bilateral orbital metastases from prostate carcinoma: case presentation and CT
      findings.
AB  - A patient with known prostatic cancer presented with bilateral orbital masses. On
      CT there was a bulky soft-tissue mass in the cranial aspect of each orbit. An
      open biopsy revealed undifferentiated tissue  that stained strongly positive for
      prostatic-specific acid phosphatase, confirming the diagnosis of metastatic
      prostate carcinoma.

PMID- 7726095
TI  - Annotated bibliography.

PMID- 7726096
TI  - Whose liability is it? The pharmacist on trial.

PMID- 7726097
TI  - Estimating possible fraud in coal mine operators' samples of respirable dust.
AB  - Coal mine operators are required to sample miners' exposure to respirable dust on
      a regular basis. A method has been developed for screening all operator samples
      for detecting possible instances of fraud. This method relies on the occurrence
      of very low concentration (VLC = 0.1 mg/m3) samples more frequently than
      expected. The number of underground mine sections from which 50% or more of all
      samples for FY 1990 were VLC (VLC-50 sections) was compared to the expected
      number, which was estimated by assuming that the occurrence of VLC samples could
      be described with a binomial probability distribution. Out of 1983 continuous
      mining sections, there were 147 VLC-50 sections vs. 7.3 expected (O/E = 20.1).
      Moreover, these 147 sections occurred more frequently than expected among small
      as opposed to large mines. For sections using conventional mining methods, 19 of
      175 were VLC-50 vs. 0.9 expected (O/E = 20.8). There was one VLC-50 longwall
      section vs. 0.003 expected. For 99 bituminous and anthracite hand-loading
      sections the observed number of VLC-50 sections was 65 vs. 78 expected (O/E =
      0.8). It is suggested that, except for hand-loading and longwall sections,
      sampling programs should be investigated at mines with VLC-50 sections.

PMID- 7726098
TI  - The effect of size and fabric weight of protective coveralls on range of gross
      body motions.
AB  - This study evaluated the effects of garment size and fabric weight on range-of
      motion (ROM). Ten male subjects performed a series of twelve gross body movements
      while wearing each of nine similarly styled coveralls. The coveralls were
      undersized, appropriately sized, and oversized, and were constructed from three
      different weights of poly/cotton fabric. A balanced 3 x 3 repeated measures
      experimental design was used, along with a seminude control condition. ROM was
      measured with a two-arm manual goniometer. Garment size significantly affected (p
      < .05) ROM for all movements except shoulder extension and trunk lateral flexion.
      Compared to seminude ROM, undersized garments reduced the mean ROM by as much as
      24% in the case of hip flexion. Fabric weights on ROM were significant for
      shoulder extension and elbow, hip, knee, and shoulder horizontal flexion. Fabric
      weight affected ROM less than garment size. Interaction effects between fabric
      weight and size generally were not significant. These results demonstrate that
      undersized garments can measurably reduce the wearer's movement capability.
      Providers of protective clothing should ensure that garments are not undersized
      and should consider the benefits of oversizing against possible safety and wearer
      acceptance problems.

PMID- 7726100
TI  - Acute and subchronic neurotoxicity studies with tri-N-butyl phosphate in adult
      Sprague-Dawley rats.
AB  - Male and female adult Sprague-Dawley rats received tributyl phosphate (TBP) in
      corn oil by gavage in acute (single-dose) and subchronic (three-month) studies.
      Dosage levels in the acute study were 100, 325, and 1000 mg/kg; they were 32.5,
      100, and 325 mg/kg/day in the subchronic study. Behavioral evaluations were
      performed in both studies, and neuropathological evaluations were performed in
      the three-month study only. The methods used in the studies are as described in
      the U.S. Environmental Protection Agency neurotoxicity guidelines. Mean body
      weight decreases were statistically significant compared to controls for male
      rats at the high-dosage level only in the acute study. Transient changes only,
      attributable to the general toxicity of the material, were noted in forelimb grip
      strength and mean activity level during the first 24 hours after dosing for 1000
      mg/kg rats. In the subchronic study high-dose males and females had statistically
      significant body weight decreases; some mortality also was observed at this
      dosage level. The motor activity levels and qualitative and quantitative
      functional observational battery measurements were comparable between treatment
      and control groups, and there were no gross or neurohistopathological findings in
      the rats indicative of treatment-related effects. Based on these study results,
      TBP was not neurotoxic to rats following either acute or subchronic exposures.

PMID- 7726099
TI  - Comparisons between magnetic field exposure indices in an automobile transmission
      plant.
AB  - Personal monitoring of extremely low frequency magnetic fields was conducted at a
      large automatic transmission plant for a case-control study of primary brain
      cancer. Current workers were selected to represent the jobs most commonly held by
      study subjects. Several exposure indices, corresponding to different plausible
      biological mechanisms, were computed for each of 81 workers who wore the
      monitoring instrument for one-half shift. Average exposures covered a range from
      0.16 to 46 mG; median exposure was 1.3 mG. Nonparametric correlations were
      estimated to learn whether all of these indices rise and fall together. Results
      were mixed, in that indices sensitive to high values showed correlations above
      0.7, but other correlations were between 0.4 and 0.6. Different indices may thus
      identify different groups as "highly" exposed. The authors also tested whether
      indices based on the fraction of time spent above hypothesized thresholds were
      accurately predicted by a lognormal model. For 47% of the workers, the observed
      indices significantly exceeded those predicted by such a model, suggesting that
      lognormality is not a good model for distributions of individuals' short-term
      exposures.

PMID- 7726101
TI  - Most comfortable loudness shift as a measure of speech attenuation by hearing
      protectors.
AB  - The feasibility of using most comfortable loudness (MCL) as a real-world measure
      of speech attenuation introduced by hearing protection devices (HPDs) was
      studied. The authors compared three insert HPDs and an earmuff under three test
      conditions: (a) monaural earphone listening, (b) binaural earphone listening, and
      (c) sound field listening. The earmuff was used only in the sound-field
      condition. In addition, three sets of fitting instructions were utilized. Twelve
      normal hearing subjects participated. Results indicate that MCL shift can be used
      as a simple measure of speech attenuation provided by HPDs. The observed MCL
      shifts were affected by the fitting instruction but not by the listening
      condition. Findings support the notion that MCL-based tests of speech attenuation
      by HPDs can be conducted reliably both in sound field and under earphones and may
      be a simple and valid tool for assessing changes in speech audibility due to the
      wearing of HPDs.

PMID- 7726102
TI  - VOC emission rates and emission factors for a sheetfed offset printing shop.
AB  - Emission rates were determined during production for a sheetfed offset printing
      shop by combining the measured concentrations and ventilation rates with mass
      balance models that characterized the printing space. Air samples were collected
      simultaneously on charcoal tubes for 12 separate 1-hour periods at 6 locations.
      Air samples and cleaning solvents were analyzed by gas chromatography for total
      volatile organic compounds (VOC) and 13 hydrocarbons. The average VOC emission
      rate was 470 g/hr with a range of 160-1100 g/hr. These values were in good
      agreement with the amounts of VOC, hexane, toluene, and aromatic C9s determined
      from estimated solvent usage and measured solvent compositions. Comparison of the
      emission rates with source activities indicated an emission factor of 30-51 g
      VOC/press cleaning. Based on the test observations it was estimated that this
      typical small printing facility was likely to release 1-2 T VOC/year. The
      methodology also may be useful for the surface coating industry, as emission
      rates in this study were determined without recourse to a temporary total
      enclosure and without interfering with worker activities, increasing worker
      exposure, or increasing safety and explosion hazards.

PMID- 7726103
TI  - Arsenic levels in hair of workers in a semiconductor fabrication facility.
AB  - This study examined the relationship between total arsenic levels in hair of
      employees in a semiconductor fabrication facility and job responsibility, a
      surrogate variable for arsenic exposure potential. Maintenance personnel who
      regularly worked in equipment cleaning areas were assumed to have higher
      potential for occupational exposure than other employees. Occipital scalp hair
      samples were collected from 30 maintenance personnel, supervisors, and equipment
      engineers with high, medium, and low potential for exposure and from 26
      administrative employees. Total arsenic in hair was measured by atomic absorption
      spectroscopy with hydride generation. Workplace air and wipe samples were
      analyzed to verify differing exposure potential in fabrication and administrative
      areas. Subjects completed written questionnaires to identify possible
      nonoccupational sources of arsenic. Mean hair arsenic in two of the three groups
      working in or near fabrication areas was slightly higher but not statistically
      different from that of administrative controls. Eliminating smokers, only the
      maintenance group regularly assigned to fabrication areas was higher than
      administrative controls but still not statistically different. A regression
      analysis of all factors indicated that sex, tapwater consumption, and dietary
      habits were significant contributors to arsenic in hair. Trends among these
      groups were consistent with expected exposure potential, although not
      dramatically different from controls. Main study conclusions were that (1)
      nonoccupational sources of arsenic can be expected to contribute more to hair
      levels in employees than that observed in this particular semiconductor work
      environment, where safe work practices were believed to be followed; and (2)
      monitoring should be considered in this industry to identify employees
      experiencing chronic, low-level arsenic exposures only if the facility also
      examines nonoccupational sources of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726104
TI  - Blood lead surveys of communities in proximity to lead-containing mill tailings.
AB  - In former mining communities tailings containing up to 2% (20,000 ppm) lead (Pb),
      frequently as galena (lead sulfide), may be present in large piles near
      residences, as landfill under homes, or mixed with residential soils. The impact
      of tailings on blood lead was assessed by comparing blood lead values obtained
      from residents and environmental lead measured in soils and tailings piles. Data
      from 13 communities were compiled. Approximately 2995 blood lead measurements
      were available from persons residing on or near tailings, with the majority of
      samples from children. Blood lead levels were compared to 1806 controls from
      nearby communities, national norms, and communities with active smelters. Data
      comparisons indicated that blood lead values in tailings residents were usually
      comparable to controls. These data suggest that lead present in mill tailings is
      not readily bioavailable, even to children who played in dirt or tailings piles.
      Consequently, the hazard of lead in soils appears to be site-specific and
      influenced by bioavailability; the bioavailability of galena tailings to humans
      is low. When health risks of lead soils are predicted, factors affecting the
      bioavailability of lead present in tailings need to be taken into account.

PMID- 7726105
TI  - Substitution of dangerous chemicals--the solution to problems with chemical
      health hazards in the work environment?
AB  - For many years efforts have been made toward the substitution of less toxic
      chemicals for particularly toxic ones. Substitutions have been made mainly on the
      basis of the toxic effect of the virgin compound on humans and the environment, a
      rationale that may be open to question. This study evaluated a number of
      substitutions made in recent years. To identify effects on the work and external
      environments, the chemical products were studied in use within a production
      system. The main observation was that substitution is a very complex process that
      might have drawbacks as well as beneficial effects, since new problems may arise
      through the use of new chemicals. In some cases, knowledge about the extent of
      these new problems is inadequate, since the substitutions are sometimes not well
      documented. Substitution may result in reduced use or discontinuance of the
      original toxic substance and may affect the external as well as the workplace
      environment.

PMID- 7726106
TI  - The effect of relative humidity on mouse allergen levels in an environmentally
      controlled mouse room.
AB  - To determine the effect of humidity on the levels of the mouse allergen Mus m 1,
      an experimental animal room was constructed to control environmental variables.
      The sex, strain, age, and number of mice was constant in the room, so that the
      average daily production of Mus m 1 would not vary greatly. Six different levels
      of relative humidity from 15% to 65% were maintained for a minimum of a week
      each. Daily collections of airborne particulates were eluted from filters and Mus
      m 1 content measured by immunological assay. Increasing relative humidity caused
      a decrease in Mus m 1 levels from a high of 3 ng/m3 at 15% humidity to a low of
      0.5 ng/m3 at 65% humidity. Thus, reduction of airborne allergen levels can be
      achieved by careful attention to humidity control, especially during the winter
      heating season when humidity levels may be low. This experimental room can be
      used to measure the effect of other variables such as ventilation rate, caging,
      bedding, and work practices on the levels of mouse allergen in an animal
      facility.

PMID- 7726107
TI  - The Evolving Role of Cardiac Imaging in the Assessment of Coronary Artery
      Disease. Proceedings of a symposium. Carlsbad, California, February 26-27, 1994.

PMID- 7726108
TI  - Optimizing patient selection for coronary angiography.
AB  - Indications for coronary angiography depend on the patient's clinical
      presentation. In many situations, coronary angiography may be reserved for
      patients who have severe symptoms, despite optimal medical therapy, and for
      patients defined to be at high risk, based on noninvasive stress testing. These
      patient groups include those with chest pain syndromes, postmyocardial
      infarction, unstable angina, postcoronary revascularization, severe left
      ventricular dysfunction, survivors of sudden cardiac death, and those about to
      undergo major vascular noncardiac surgery.

PMID- 7726109
TI  - Technical, economic, interpretative, and outcomes issues regarding utilization of
      cardiac imaging techniques in patients with known or suspected coronary artery
      disease.
AB  - In this article, the technical and economic issues that determine the utilization
      of tests used for cardiac imaging in patients with known or suspected coronary
      artery disease are discussed. The interpretative and outcomes issues that should
      determine the utilization of such tests are also discussed. In this regard,
      special emphasis is placed on, among other issues, the level of training and
      competence, the pretest probability of disease, the incremental value of a test
      in the context of what is already known about a patient, and whether risk
      stratification is justified when risk management is not possible.

PMID- 7726110
TI  - Comparison of stress echocardiography and stress myocardial perfusion
      scintigraphy for diagnosing coronary artery disease and assessing its severity.
AB  - The cumulative published literature dealing with the most frequently utilized
      noninvasive cardiac stress imaging modalities (radionuclide myocardial perfusion
      scintigraphy and echocardiography) was reviewed to gain insight on their
      comparative diagnostic accuracies. To be included, studies had to be performed in
      conjunction with exercise or a commonly used intravenous pharmacologic stress
      agent (dipyridamole, adenosine or dobutamine) and had to report temporally
      related coronary angiography findings. A total of > 75 studies were included,
      involving > 7,000 patients. Exercise single-photon emitted computed tomographic
      (SPECT) scintigraphy was more sensitive than exercise echocardiography for
      detecting coronary artery disease (CAD), localizing it to the proper coronary
      artery distribution and correctly identifying the presence of multivessel CAD.
      Adenosine, dipyridamole, and dobutamine provided similar diagnostic accuracy when
      performed in conjunction with SPECT scintigraphy, and all were more accurate than
      dobutamine echocardiography. Clinical specificity was similarly high with
      adenosine SPECT, dipyridamole echocardiography, and exercise echocardiography,
      and lower with exercise SPECT. Normalcy rate was high for exercise SPECT and
      similar to clinical specificity for echocardiography.

PMID- 7726111
TI  - Clinical applications of exercise nuclear cardiology studies in the era of
      healthcare reform.
AB  - The challenge for nuclear cardiology is to demonstrate that it can provide more
      information than competitive modalities at comparable or lower cost. In
      considering patients for nuclear cardiology procedures, presentations can be
      divided into 9 subsets: within each subset, nuclear cardiology tests should be
      employed where incremental information is provided over the information available
      without performing the test. (1) Patients with no known coronary artery disease
      (CAD); for diagnosis, nuclear imaging is useful in patients with intermediate
      probability of CAD. For prognosis, assessment is based on extent of ischemia,
      where we have shown that nuclear testing provides incremental information,
      especially in patients with a high likelihood of CAD, such as those with typical
      angina. In the remaining categories (2-9), nuclear cardiology studies are
      predominantly used for purposes of risk stratification. Here the greatest value
      is in patients deemed to be at intermediate risk before nuclear testing. (2)
      Postmyocardial infarction: stress nuclear imaging provides an alternative to
      angiography for risk assessment of clinically uncomplicated patients. (3) Poor
      ventricular function: Nuclear testing is particularly useful for differentiating
      patients with hibernating myocardium (the defect is reversible), with stunned
      myocardium (no defect is present), or with myocardial infarction (the defect is
      persistent). (4) Unstable angina: Following current federal guidelines, nuclear
      imaging in medically stabilized low-to-intermediate risk patients with unstable
      angina is likely to increase. (5) Postcatheterization patients: Nuclear imaging
      is useful when there is uncertainty regarding the choice of medical management or
      revascularization. (6) Pre-noncardiac surgery patients: Nuclear imaging is
      clearly helpful in patients with intermediate clinical risk and may provide
      useful information in clinically high-risk patients. (7) Post-PTCA patients: Due
      to the intermediate likelihood of restenosis, nuclear scans are frequently
      employed 2-6 months following intervention. (8) Post-CABG patients: We have
      demonstrated that exercise scintigraphy (SPECT) provides incremental prognostic
      information over clinical and exercise electrocardiographic results and is useful
      when clinical risk of events is considered intermediate. (9) Long-term
      management: Scintigraphy provides objective information regarding progression or
      regression of CAD.

PMID- 7726112
TI  - Prognostic value of cardiac imaging in patients with known or suspected coronary
      artery disease: comparison of myocardial perfusion imaging, stress
      echocardiography, and position emission tomography.
AB  - Prior studies have suggested that, compared with angiographic, exercise
      electrocardiographic, and clinical data in patients with known or suspected
      coronary artery disease (CAD), the data provided by exercise thallium-201
      scintigraphy are the best predictor of cardiac events. The most consistent
      finding is that the presence and extent of jeopardized viable myocardium,
      manifest by transient thallium-201 defects, predicts cardiac events. In addition,
      a normal thallium-201 scan reliably predicts an annual event rate for cardiac
      death or nonfatal myocardial infarction of < 1% per year, a rate approaching that
      of a normal aged-matched population. Further, it has been demonstrated that the
      incremental prognostic value of transient thallium-201 defects is statistically
      significant and nearly double that of clinical data and stress
      electrocardiography combined, and, importantly, not significantly different from
      that obtained by adding angiographic data. These results appear to hold for the
      newer, technetium-99m-based perfusion agents such as sestamibi, for which
      sensitivity and specificity for detecting CAD are comparable. Stress
      echocardiography, which depends on development of a secondary phenomenon
      (abnormal wall motion), appears to be less sensitive for the detection of CAD
      than myocardial perfusion imaging (which can detect the primary insult,
      hypoperfusion); stress echocardiography is also less sensitive for detection of
      jeopardized viable myocardium. Because of its lower sensitivity for detecting
      jeopardized viable myocardium, stress echocardiography may underestimate the risk
      of cardiac events, especially in patients with known CAD. Thus it may not
      reliably identify a low-risk group, especially in patients with known
      CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726113
TI  - Preoperative cardiac risk assessment for noncardiac surgery.
AB  - Coronary artery disease (CAD) represents an important risk in patients undergoing
      elective noncardiac surgical procedures, in whom the stress of surgery and
      postoperative recovery can represent a significant ischemic burden. Population
      considerations: Preoperative cardiac assessment should be based on the prevalence
      of CAD (if known) in the population undergoing the procedure and the
      institutional event rate for the procedure. Procedures considered high-risk are
      vascular, intra-abdominal or thoracic, major orthopedic, and any emergency
      procedures. Individual considerations: CLINICAL HISTORY: A history of angina,
      congestive heart failure, diabetes mellitus, prior myocardial infarction,
      ventricular ectopy, and/or elderly (age > 70) are clinical parameters of
      increased risk. Functional capacity: Good functional capacity is the ability of a
      50-70-year-old patient to achieve 6-8 METS of activity without significant
      symptoms of dyspnea on exertion. Further noninvasive testing: Preoperative
      testing may include routine treadmill exercise testing, ambulatory ECG
      monitoring, echocardiographic stress testing with dobutamine or exercise, and/or
      thallium perfusion imaging. Strategy for high risk patients: Assessing the
      severity of an abnormality (e.g., with thallium) results in a small percentage of
      positive test results yielding a high positive predictive value for events.
      Therefore, more aggressive interventions should be reserved for the most abnormal
      noninvasive test results, and the severity of the risk assessment should impact
      the timing of any coronary revascularization procedure, not the decision to
      proceed to more invasive testing and therapies. In summary, it is important to
      realize that most of the patients being screened, even vascular surgery patients
      (with high prevalence of CAD and procedural risk), will be found suitable to go
      to surgery without additional invasive intervention and cardiac
      revascularization. Thus good functional capacity and absence of cardiac risk
      factors should direct 30-40% of this population to elective surgery without
      further evaluation. The finding of high-risk perfusion scan abnormalities appears
      to be limited to 15-20% of those patients being recommended for further
      noninvasive testing.

PMID- 7726114
TI  - Diagnostic testing strategies for coronary artery disease: special issues related
      to gender.
AB  - Early reports of the prevalence, diagnosis, and outcomes of coronary artery
      disease (CAD) in women have led to the acceptance of several myths concerning
      noninvasive diagnostic studies in women. Many of the myths can be explained by
      age-related differences in prevalence, methodological errors that exclude women
      from enrollment, worse clinical baseline risk profiles, comorbid diseases at the
      time of interventions, and smaller coronary vessels. Awareness of these age
      related prevalence factors in women and the potential for delaying the onset of
      CAD by estrogen treatment in postmenopausal women must be considered in assessing
      the accuracy of diagnostic studies. The critical role of noninvasive testing in
      women is to diagnose CAD accurately in a population with a lower prevalence of
      disease prior to the development of more severe clinical manifestations when
      therapeutic interventions have a high risk and a poor outcome. Exercise
      radionuclide ventriculography has lower specificity in women, which may be due to
      gender differences in the response to exercise. Radionuclide perfusion imaging
      for the detection of CAD is accurate, there is extensive published literature,
      and it is used widely. High-dose dipyridamole in combination with
      echocardiography is not widespread in the United States; most pharmacologic
      echocardiographic studies are performed using dobutamine, and there are no
      reports on gender differences using dobutamine echocardiography.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7726115
TI  - Myocardial contrast echocardiography in coronary artery disease: potential
      applications using venous injections of contrast.
AB  - The feasibility of studying myocardial perfusion with myocardial contrast
      echocardiography using intra-aortic or intracoronary injections of contrast
      medium has been established both in animal models and humans. However, the
      assessment of myocardial perfusion using venous injection is dependent on the
      availability of contrast agents that can opacify the left ventricular myocardium
      following a venous injection. Such agents are currently being evaluated in animal
      models. Using data from left atrial injections of contrast, this review briefly
      highlights the principles that govern the study of myocardial perfusion from
      venous injections of contrast. The value of such an approach in the setting of
      chronic coronary artery disease and acute myocardial infarction is discussed.

PMID- 7726116
TI  - Beyond perfusion with ultrafast computed tomography.
AB  - Ultrafast computed tomography (CT) has been available for the clinician for
      nearly 10 years. Although cost, as well as availability of competing
      technologies, have limited its application, several investigative groups have
      demonstrated the feasibility of measuring regional myocardial blood flow by this
      method. Ultrafast CT provides accurate measurements when myocardial blood flow is
      normal or reduced. However, when flow is increased (e.g., by pharmacologic
      vasodilation), the technique underestimates flow. (This can apparently be
      corrected by using a complex curve-fitting technique.) Direct injection of
      contrast medium into the aorta distinguishes differences in endocardial and
      epicardial blood flow. Although imaging of myocardial perfusion has proven
      clinical value, there is a need for new noninvasive approaches for detecting
      silent coronary atherosclerosis before coronary events occur. Here it is possible
      to make use of the close association between coronary atherosclerosis and
      coronary intimal calcium, recognized over 35 years ago. Even though the amount of
      coronary calcium is a function of age, individuals with coronary artery disease
      usually have greater amounts, and the greater the number of coronary vessels with
      calcium, the greater the likelihood of obstructive coronary disease. Ultrafast CT
      has proven value for visualizing coronary calcium. No contrast medium is required
      and radiation exposure is approximately 425 mrads.

PMID- 7726117
TI  - The evolving role of MRI in the assessment of coronary artery disease.
AB  - Magnetic resonance imaging (MRI) methods are positioned to make a major impact in
      the care of patients with ischemic heart disease. Further advances are to be
      expected in the area of myocardial perfusion imaging and noninvasive MRI coronary
      "angiography." Work also continues in determining quantitative flow via MRI.
      Although expensive, the unique ability of MRI methods to provide multiple pieces
      of information in a single examination may make this technology cost effective.
      The concept of a "one-step shop" is progressing steadily toward a clinical
      reality.

PMID- 7726118
TI  - The vicious circle of ischemic left ventricular dysfunction.
AB  - Myocardial ischemia tends to be self-propagating, and minor events such as plaque
      rupture can lead to the catastrophic sequelae of myocardial infarction and death.
      The biology of the endothelium and the cardiac myocyte is crucial to the
      development of these vicious circles. The abnormal responses of the endothelial
      cell in atherosclerosis tend to provoke and propagate ischemia, and because of
      the limited metabolic reserve of the myocyte, even short periods of ischemia can
      lead to left ventricular dysfunction and arrhythmias. This article examines the
      clinical implications of the disordered biology of the endothelial cell and the
      myocyte that is the basis for ischemic left ventricular dysfunction.

PMID- 7726119
TI  - From coronary artery disease to heart failure: role of the hibernating
      myocardium.
AB  - Hibernating myocardium is defined as persistently impaired myocardial and left
      ventricular (LV) function at rest resulting from reduced myocardial blood flow.
      It may occur in unstable angina and chronic stable angina, acute myocardial
      infarction, and LV dysfunction and congestive heart failure. Recovery of the
      hibernating myocardium has clearly been shown to occur with the establishment of
      successful revascularization either by coronary bypass surgery or by percutaneous
      transluminal coronary angioplasty. It may be possible to show recovery of the
      viable myocardium by reducing myocardial oxygen demand and/or by increasing
      coronary blood flow with pharmaceutical agents.

PMID- 7726120
TI  - Clinical and therapeutic implications of chronic left ventricular dysfunction in
      coronary artery disease.
AB  - In patients with myocardial ischemia, left ventricular dysfunction (LV) may arise
      from irreversible damage (cell death), myocardial stunning (postischemic
      dysfunction), or myocardial hibernation (persistent myocardial dysfunction at
      rest due to underperfusion). Chronic LV dysfunction usually refers to hibernating
      myocardium. However, stunning might also become chronic, producing persistent
      myocardial dysfunction. Clinical studies have demonstrated that many patients
      with coronary artery disease have subsequent recurring ischemic (symptomatic or
      silent) episodes at short intervals in the same area and that each episode may be
      followed by myocardial stunning. In these patients the myocardium may not recover
      fully between episodes and function may remain reversibly depressed for long
      periods or may even be clinically depressed. The recognition of both stunning and
      hibernation is very important clinically and therapeutically, since chronic LV
      dysfunction may have a negative effect on mortality and morbidity in patients
      with coronary artery disease. Moreover, both clinical states are potentially
      correctable. Pharmacologic intervention with beta blockers, angiotensin
      converting enzyme inhibitors, or calcium antagonists might improve or protect
      hibernating myocardium. The acute hemodynamic effects of the dihydropyridine
      calcium antagonist nisoldipine have been investigated in patients with chronic LV
      dysfunction probably arising from hibernating myocardium. Nisoldipine was found
      to improve both left ventricular systolic and diastolic function without
      activating the adrenergic system. The improvement in systolic function may be due
      to a redistribution of coronary blood flow and to a slight reduction in afterload
      induced by nisoldipine. On the other hand, nisoldipine may improve diastolic
      function in these patients by an intrinsic mechanism, Reducing intracellular
      calcium overload or balancing intracellular calcium homeostasis in the ischemic
      areas.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726121
TI  - Perfusional and metabolic effects of nisoldipine as shown by positron emission
      tomography after acute myocardial infarction.
AB  - After myocardial infarction, regional dysfunction can occur in viable myocardial
      regions because of the presence of baseline hypoperfusion. Recent evidence
      suggests that these areas may maintain a residual perfusion reserve. The aim of
      the present study was to evaluate whether oral nisoldipine can increase regional
      myocardial blood flow (MBF) in dyssynergic but viable myocardium after myocardial
      infarction. Patients with isolated left anterior descending coronary stenosis
      were studied 1 month after the first myocardial infarction. Patients underwent
      [18F]fluorodeoxyglucose imaging, and MBF was measured, using positron emission
      tomography and [13N]ammonia, at baseline and following dobutamine administration
      (10 micrograms/kg/min over 5 minutes). MBF measurements were repeated 24 hours
      after nisoldipine (10 mg twice daily). Preliminary results suggest that necrotic
      areas showed the largest reduction in baseline MBF. Dyssynergic-viable regions
      showed a reduced resting MBF but maintained a residual perfusion reserve in
      response to inotropic stimulation. Thus, nisoldipine selectively improved basal
      perfusion in dyssynergic-viable myocardium.

PMID- 7726122
TI  - Why is nisoldipine a specific agent in ischemic left ventricular dysfunction?
AB  - Nisoldipine is a dihydropyridine calcium entry blocker that inhibits contraction
      of vascular smooth muscle with a potency that is 2-3 times greater than its
      impact on myocardial contractility. In isolated human coronary arteries, tonic
      contractions induced by serotonin are inhibited by nisoldipine with a potency 10
      times greater than that in internal mammary arteries and 1,000 times greater than
      that in electrically driven myocardium. In contrast, nifedipine had little effect
      and verapamil and diltiazem had none. In this article an hypothesis is reviewed
      that relates vascular smooth muscle selectivity to membrane potential
      sensitivity. Nisoldipine's effect on calcium channel binding and blocking is
      enhanced by the degree of depolarization of the cell membrane. Verapamil and
      diltiazem are not membrane-potential sensitive. Vascular smooth muscle cells are
      more depolarized than myocardial cells, and human coronary arteries have a
      particularly small membrane potential. Thus, the potency of nisoldipine in these
      organs parallels the degree of membrane depolarization. This may then suggest
      ischemia selectivity, since membrane depolarization occurs in ischemic tissue.
      Nisoldipine might therefore have a potent negative inotropic effect and an
      enhanced vasodilator action in ischemic myocardium, yet leave normoxic regions
      functionally intact. Some experimental evidence is discussed.

PMID- 7726123
TI  - Angiotensin-converting enzyme inhibitors and calcium antagonists after acute
      myocardial infarction.
AB  - This article examines trials of the use of two types of drugs in the treatment of
      myocardial infarction: angiotensin-converting enzyme (ACE) inhibitors and calcium
      antagonists. ACE inhibitors are an established treatment for hypertension and
      heart failure and have been shown to reduce mortality from heart failure and
      after myocardial infarction. Six large studies have been carried out. In 1 in
      which an ACE inhibitor was given 3-16 days after infarction in patients with an
      ejection fraction < 40%, mortality was reduced by 17%. In a second study of
      patients who had evidence of heart failure and were followed up for 15 months,
      treatment with ACE inhibitors was given 3-10 days after myocardial infarction and
      mortality was reduced by 27%. Two other studies of 11,000 and 50,000 unselected
      patients with myocardial infarction showed only marginal clinical benefit.
      Calcium antagonists were introduced to treat hypertension and angina pectoris. In
      trials with patients with heart failure, the results have not been encouraging,
      and in some patients these agents seem to be harmful. Recently, long-acting
      calcium antagonists have become available, and these may avoid the deleterious
      effects of short-acting drugs. Since calcium antagonists act on smooth muscle,
      they may increase myocardial blood flow to improve function after "stunning" or
      "hibernation." This idea was investigated with a long-acting dihydroyridine
      calcium, antagonist in a randomized double-blind, placebo-controlled study
      (Doppler Flow, Echocardiography, and Functional Improvement Assessment of
      Nisoldipine Therapy-I--DEFIANT I), and a further study is being carried out. At
      present the widespread use of calcium antagonists after infarction is not
      recommended.

PMID- 7726124
TI  - Clinical pharmacology of nisoldipine coat core.
AB  - Nisoldipine is a second-generation dihydropyridine calcium antagonist
      structurally related to nifedipine and used in the treatment of stable angina and
      arterial hypertension. It is also under investigation for the treatment of left
      ventricular dysfunction. It was first developed as an immediate release tablet,
      but this formulation was not considered optimal for once-daily administration
      because of the variable results obtained at peak and trough in clinical studies.
      Consequently, nisoldipine coat core (CC) was developed with the aim of optimizing
      the drug's time--effect profile over the 24-hour dosing interval. The in vitro
      release pattern classifies this tablet as an "extended release" formulation
      according to European Community guidelines. The present article outlines the
      pharmacokinetic and pharmacodynamic profiles of nisoldipine CC, as obtained from
      recent clinical studies.

PMID- 7726125
TI  - Efficacy and safety of nisoldipine coat core in the management of angina
      pectoris, systemic hypertension, and ischemic ventricular dysfunction.
AB  - The effects of the long-acting dihydropyridine calcium antagonist nisoldipine
      coat core (CC) have been investigated in > 3,500 patients with angina pectoris,
      hypertension, and ischemic ventricular dysfunction. In patients with angina
      pectoris, nisoldipine CC improved total treadmill exercise duration (p = 0.027),
      delayed the onset of angina pectoris (p = 0.009), and increased time to exercise
      induced ST-segment depression (p = 0.061). In general, nisoldipine 20-40 mg was
      effective, and the dose-response curve flattened thereafter. In patients with
      hypertension, 10-40 mg once daily as monotherapy reduced blood pressure (p <
      0.05), with a fall in diastolic pressure of > or = 10 mm Hg or a final diastolic
      pressure of < 90 mm Hg in 35-63% of patients. In most patients followed for a
      year, nisoldipine CC was continued as monotherapy. Efficacy was similar in
      patients < 65 and > 65 years of age. In the Doppler Flow and Echocardiography in
      Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy (DEFIANT-I)
      study of patients recovering from myocardial infarction, nisoldipine CC had a
      salutary effect on diastolic ventricular function, with a higher transmitral
      early filling velocity and shorter isovolumic relaxation time than in patients
      receiving placebo. Bicycle exercise capacity was greater (by 12 W; 95% confidence
      interval, 0.8-23.3) and exercise-induced ischemia occurred less frequently. The
      nisoldipine CC data pool (3,679 patients) showed that the drug was well tolerated
      with a low incidence of side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726126
TI  - Effects of nisoldipine in silent myocardial ischemia after healing of acute
      myocardial infarction.
AB  - Silent myocardial ischemia occurring after acute myocardial infarction is
      classified as Cohn type II and has a frequency of 20-30% in all patients with
      acute myocardial infarction. Follow-up data of patients with either silent or
      anginal ischemia show a poor prognosis. Thus, all ischemic episodes occurring
      after myocardial infarction should be treated aggressively. Many multicenter
      studies have evaluated whether drug treatment can improve prognosis or protect
      from a nonfatal second attack. Calcium antagonists, especially those that
      increase heart rate, have not been considered as drugs of choice for this
      purpose, despite the many beneficial effects shown on myocardial tissue in
      experimental studies. In the study reported here, the effect of nisoldipine on
      postinfarction silent myocardial ischemia was evaluated by ambulatory left
      ventricular function monitoring. Ten patients were selected for study who showed
      silent myocardial ischemia after their first acute infarction. Blood pressure
      fell significantly (p < 0.05) after 4 weeks of treatment with nisoldipine (5-10
      mg/day), but heart rate showed no change at rest. Exercise time improved (p <
      0.05), with increased peak double products. During exercise, there was no
      significant change in end-diastolic volume but there was a marked improvement in
      end-systolic volume, and at the submaximal point the ejection fraction was
      significantly (p < 0.05) increased. Ejection fraction at rest also improved. The
      deterioration in ejection fraction due to dipyridamole was ameliorated by
      nisoldipine. Ejection fraction and blood pressure improved during the calculation
      test, and work performance also improved.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726127
TI  - Stunned myocardium and the attenuation of stunning by calcium antagonists.
AB  - Myocardial "stunning" is characterized by a reversible postischemic contractile
      dysfunction despite full restoration of blood flow. The underlying mechanisms are
      not clearly understood. Inadequate energy supply and impaired sympathetic
      neurotransmission may have been excluded. Potential mechanisms, which are not
      mutually exclusive, may include damage to membranes and enzymes by free radicals,
      an increase in free cytosolic calcium during ischemia and reperfusion, and a
      lower calcium sensitivity of myofibrils. The equally pronounced increases in
      regional contractility in normal and stunned myocardium during postextrasystolic
      potentiation and the infusion of calcium or the calcium-sensitizing agent AR-L
      57, however, suggest an unchanged calcium sensitivity in reperfused myocardium.
      Pretreatment with calcium antagonists before ischemia attenuates myocardial
      stunning. This effect is probably related to a lessened myocardial calcium
      overload during early ischemia. The potential benefit of treatment with calcium
      antagonists after reperfusion is established remains controversial.

PMID- 7726128
TI  - Nisoldipine coat core as concomitant therapy in chronic stable angina pectoris.
AB  - Nisoldipine is a second-generation dihydropyridine calcium antagonist that has
      been extensively studied as an antianginal and antihypertensive agent. As an
      antianginal agent, the immediate release formulation has shown significant
      activity at peak effect but less at trough. As a result, a sustained release
      formulation (coat core) has been developed. This report focuses on the studies
      evaluating the antianginal and anti-ischemic effects of nisoldipine coat core
      (NIS CC) when used alone or with add-on therapy with beta-adrenergic blocking
      agents and/or long-acting nitrates (3 long-term extension trials), or as add-on
      therapy to existent beta-adrenergic blocking treatment (in 1 double-blind, short
      term trial). The long-term extension studies all demonstrated an improvement in
      exercise test variables and a reduction in angina frequency and sublingual
      nitroglycerin usage with NIS CC when compared with baseline. Discontinuation due
      to ischemic adverse events occurred in 5.4-13.6% of patients during the 1-year
      course of these trials. However, only 2 deaths and 9 myocardial infarctions
      occurred (in 503 patients enrolled and 342 patients completing the entire 1 year
      of therapy). The short-term, double-blind study evaluated the addition of NIS CC
      (20 or 40 mg vs placebo) to existent atenolol therapy (50 mg four times daily).
      Exercise test variables at peak and trough showed a trend toward improvement,
      although these changes did not reach statistical significance. Other support for
      the efficacy of NIS CC was also demonstrated, and double-blind studies with the
      immediate release formulation have also shown improvements when nisoldipine was
      utilized as add-on therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726129
TI  - Calcium antagonists and left ventricular dysfunction.
AB  - Calcium antagonists are used in the management of a variety of cardiovascular
      disorders. Ischemia leads to left ventricular dysfunction, which is the clinical
      entity on which the calcium antagonists are expected to have their effect as a
      result of their anti-ischemic action. This article reviews the efficacy of
      calcium antagonists in several different settings of left ventricular dysfunction
      due to ischemia and reperfusion.

PMID- 7726130
TI  - Screening for dyslipidemia. Practice parameter.
AB  - Screening for serum lipid disorders is recommended by numerous specialty
      societies to identify patients at risk for coronary heart disease (CHD). The best
      screening tests will identify patients at highest risk for CHD who would benefit
      from intervention. This report discusses an appropriate test panel to use as the
      initial screen on a healthy outpatient population, and the required accuracy and
      precision of the tests from the Laboratory Medicine perspective. Controversy
      exists regarding which methods to use and at what age testing should begin. The
      following parameters will be modified as studies continue and new tests are
      developed. The recommendations are as follows: (1) Total serum cholesterol (TC)
      and high density lipoprotein-cholesterol (HDL-C) are presently the recommended
      screening tests for dyslipidemia in the general population; (2) The National
      Cholesterol Education Program (NCEP) recommends measuring TC and HDL-C in adults
      with a single sample at 5-year intervals beginning at age 20; (3) The NCEP
      recommends measuring TC in children with at least one parent having TC > or =
      6.24 mmol/L (> or = 240 mg/dL); (4) The NCEP recommends a lipoprotein analysis
      consisting of a 12-hour fasting TC, HDL-C, triglyceride, and estimated low
      density lipoprotein-cholesterol (LDL-C) in adults with the following results: (a)
      TC > or = 6.24 mmol/L (> or = 240 mg/dL); (b) borderline TC of 5.20-6.23 mmol/L
      (200-239 mg/dL) and HDL-C < 0.91 mmol/L (< 35 mg/dL) or two or more risk factors;
      (c) desirable TC of < 5.20 mmol/L (< 200 mg/dL), but HDL-C < 0.91 mmol/L (< 35
      mg/dL); (5) The NCEP recommends a lipoprotein analysis in children with
      documented CHD in a parent or grandparent, or in children that have a TC of > or
      = 5.20 mmol/L (> or = 200 mg/dL); (6) Two or three separate lipoprotein analyses
      should be done to confirm the LDL-C result before therapeutic intervention.
      Specimens should be tested from 1 to 8 weeks apart and the results averaged to
      account for physiologic variability; (7) Enzymatic methods are preferred for TC
      determination, and should be standardized and traceable to the reference method
      and materials at the Centers for Disease Control and Prevention (CDC); (8) The
      analytic method for TC should have a bias against the reference method of < 3%
      and a within laboratory reproducibility of < 3% coefficient of variation; (9)
      Chemical precipitation methods are preferred for HDL-C determination.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7726131
TI  - Biochemical discrimination of pathologic pregnancy from early, normal
      intrauterine gestation in symptomatic patients.
AB  - The authors have examined the utility of using the rate of change of the human
      chorionic gonadotropin (hCG) level and progesterone concentration to distinguish
      ectopic from normal intrauterine pregnancies. Patients suspicious for ectopic
      pregnancy had three outcomes: normal intrauterine gestation (NIUG), ectopic
      pregnancy (ECT), and inevitable abortion (IAB). The rate of change of the hCG
      level and the progesterone concentration distinguish NIUG from ECT with good
      sensitivity and specificity at optimal cut-offs of 0.14 (rate of change of the
      logarithm of hCG) and 8 ng/mL (progesterone). As the biochemical parameters of
      the ECT and IAB groups overlap, stating that NIUG can be biochemically
      distinguished from ECT is misleading. Thus, the authors have grouped them
      together as pathologic pregnancies (PATH). The rate of change of the hCG level
      and the progesterone concentration distinguish NIUG from PATH with good
      sensitivity and specificity with the same optimal cut-offs of 0.14 (rate of
      change of the logarithm of hCG) and 8 ng/mL (progesterone).

PMID- 7726132
TI  - A simple chromogenic substrate assay of tissue factor pathway inhibitor activity
      in plasma and serum.
AB  - A simple chromogenic substrate assay for the quantitation of tissue factor
      pathway inhibitor (TFPI) activity in plasma or serum samples was developed. After
      immobilization on microtiter plates for 20 hours at 4 degrees C, a commercial
      thromboplastin was incubated for 1 hour at room temperature with 1 U/mL of a
      prothrombin complex concentrate (Protromplex). After washing, solid-phase Factor
      Xa activity was measured by a chromogenic substrate (S-2222). Factor Xa
      generation was progressively inhibited when increasing amounts (1-12 microL) of
      heated serum or plasma, and recombinant TFPI (1-5 ng/mL), were coincubated with
      Protromplex. Inhibition by serum or plasma was abolished by anti-TFPI polyclonal
      antibodies. Plasma levels of TFPI in 25 healthy volunteers were found to be 0.98
      +/- 0.19 U/mL (range 0.71-1.52), with an intra- and inter-assay coefficient of
      variation of 10.7 and 11.1%, respectively. The use of a recombinant human
      thromboplastin improved the sensitivity and reproducibility of the assay. Plasma
      levels of TFPI were found to be normal in 10 women at the end of their
      pregnancies, in 10 patients receiving oral anticoagulant therapy, and in 10
      diabetic patients. Significantly higher levels were detected in 10 patients with
      chronic liver disease and in 10 patients with unexplained juvenile thrombosis. In
      patients with cardiovascular disease, a 7-day treatment with subcutaneous
      standard heparin increased TFPI activity. The availability of a simple and rapid
      assay to measure TFPI that does not require purified coagulation proteins may
      facilitate studies of the pathophysiologic relevance of this inhibitor.

PMID- 7726133
TI  - Comparison of nephelometric and hemolytic techniques for determination of
      antistreptolysin O antibodies.
AB  - The sensitivity of a newly devised nephelometric method for determining
      antistreptolysin O antibodies was compared with the hemolytic inhibition assay.
      Three hundred-thirty single serum samples from children with and without evidence
      of group A streptococcal infection were analyzed by the two techniques. The
      nephelometric method results correlated well with those of the reference test
      (concordance: r = 0.88). Furthermore, 134 pairs of acute and convalescent phase
      sera from patients with culture-proven GAS infection and 50 pairs from children
      who served as control subjects were examined. The nephelometric assay was more
      sensitive in detecting significant ASO antibody rises than the hemolytic assay.
      The automated nephelometric method appears to be a much simpler and sensitive
      procedure for testing ASO antibodies.

PMID- 7726134
TI  - Low maternal serum unconjugated estriol during prenatal screening as an
      indication of placental steroid sulfatase deficiency and X-linked ichthyosis.
AB  - Placental sulfatase deficiency is an X-linked metabolic defect that occurs in
      about 1 in 2,000 to 5,000 males. It is associated with congenital ichthyosis. In
      this report, the authors document a case of placental sulfatase deficiency
      detected during routine prenatal screening of maternal serum by the triple test:
      serum alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic
      gonadotropin (hCG). At 16-weeks gestation, her AFP was 20.9 IU/mL (multiple of
      the median [MOM] 0.83), hCG was 14.4 mIU/L (MOM 0.42) and her uE3 was 0.01 nmol/L
      (MOM 0.01). The extremely low uE3 indicated a possible placental sulfatase
      deficiency, congenital adrenal hypoplasia, or other unknown abnormality. On
      receiving this information, the obstetrician obtained a family history that was
      consistent with ichthyosis in the maternal grandfather and his siblings.
      Biochemical analysis of placenta documented the lack of sulfatase activity. This
      case illustrates that an extremely low level of maternal uE3 should prompt
      investigation of the family for evidence of X-linked ichthyosis associated with
      placental sulfatase deficiency.

PMID- 7726135
TI  - PCR-detection of tumor-derived p53 DNA in cerebrospinal fluid.
AB  - The sensitivity of polymerase chain reaction (PCR)-based methods for the
      detection of DNA offers opportunities for tumor diagnosis from the small amounts
      of tumor-derived DNA released into body fluids. Tumor-derived DNA can be
      distinguished from DNA derived from non-neoplastic cells by the presence of tumor
      specific genomic alterations, such as mutations in the p53 gene. This case report
      describes the use of allele-specific PCR (A-PCR) to detect a C-->T transition in
      p53 codon 273 in DNA extracted from the cerebrospinal fluid (CSF) of a patient
      whose glioblastoma contained the same mutation. The results of this study were
      confirmed by a second independent A-PCR reaction that detected the corresponding
      G-->A transition on the opposite strand. The specificity of the A-PCR protocol
      was demonstrated by negative controls, including pooled human placental DNA and
      the patient's non-tumor DNA, and by the use of A-PCR primers to detect all four
      possible bases at the site of the mutation. The methodology used in this study is
      suitable for use as a diagnostic clinical test. Because about half of all human
      tumors contain p53 mutations, PCR examination of CSF for the presence of mutant
      p53 sequences may be useful in the diagnosis of recurrent or metastatic tumors.
      Patients with known carcinoma of the breast or lung might be particularly
      benefited by this test.

PMID- 7726136
TI  - Ploidy analysis of products of conception by image and flow cytometry with
      cytogenetic correlation.
AB  - Ploidy analysis of hydropic placentas is used in conjunction with morphology and
      clinical data to classify hydatidiform moles and hydropic abortuses. In most
      studies, ploidy has been assessed by flow cytometry (FCM). To validate image
      cytometry (ICM) as a method to determine ploidy in this setting, the authors used
      both FCM and ICM to study 19 hydropic placentas in which cytogenetic analysis was
      available. Nuclear suspensions from paraffin-embedded tissue were used for both
      ICM and FCM. Image cytometry of tissue sections was performed in some cases.
      Image cytometry and FCM were concordant in all 19 cases, but discordant with
      cytogenetics in 2 of 19 cases. Two hydropic abortuses (HA) with a diploid
      karyotype were triploid and tetraploid, respectively, by both ICM and FCM, which
      suggested that the cultured tissue was not representative. DNA indices were most
      accurate when an internal diploid control was used as the reference. In ICM,
      higher resolution was achieved by analyzing cell suspensions rather than tissue
      sections. This study shows that ICM is a valid method of determining ploidy of
      hydropic placentas and partial hydatidiform moles in archival tissue.

PMID- 7726137
TI  - Pathologic examination of fetal specimens from dilation and evacuation
      procedures.
AB  - The systematic examination of fetal specimens obtained from dilation and
      evacuation (D & E) procedures with termination of pregnancy for fetal
      malformations and chromosomal abnormalities is described. Although a D & E
      procedure does not yield an intact fetus, pathologic examination of fetal parts
      by use of radiography, gross dissection, microscopic examination, and/or cell
      culture for karyotyping or biochemical analysis can aid in confirming most
      prenatal clinical diagnoses or provide a specific diagnosis. In this study, a
      major abnormality could be detected in 92% of 37 D & E cases examined, and in 46%
      a specific diagnosis was obtained only from pathologic examination. This
      information is useful for genetic counselling and future family planning.

PMID- 7726138
TI  - KP1/CD68 expression in malignant neoplasms including lymphomas, sarcomas, and
      carcinomas.
AB  - Expression of KP1/CD68 macrophage-associated antigen in a series of 840 selected
      malignant neoplasms, including immunomorphologically characterized cases of non
      Hodgkin's lymphoma (NHL) (434), Hodgkin's disease (HD) (115), soft tissue sarcoma
      (147), carcinoma (49), and other tumors (95), was examined. KP1 expression was
      detected in a significant number of NHLs (107 of 434; 24.7%), most of them (65 of
      107; 60.7%) of the diffuse small cell subtype. Only 14 of the 155 large cell
      lymphomas, compared to 10 of the 51 Ki-1/CD30+ anaplastic large cell (ALC)
      lymphomas examined, were KP1 positive. Conversely, none of the T-lineage NHL-
      other than Ki-1/CD30+ ALC lymphomas--or the HD cases tested was labeled by KP1
      antibody. Among the other neoplasms tested, KP1 was reactive with a variable
      proportion of cases of malignant fibrous histiocytoma (19 of 24; 79.2%),
      malignant schwannoma (8 of 22; 36.4%), liposarcoma (3 of 9; 33.3%),
      leiomyosarcoma (8 of 37; 21.6%), cutaneous or metastatic melanoma (51 of 73;
      69.9%), and renal cell carcinoma (3 of 5; 60%). These results indicate that KP1
      shows a relatively wide spectrum of immunoreactivity with malignant neoplasms of
      presumed non-histiocyte origin, thus arguing against its expected specificity and
      high value in diagnostic pathology. Although the significance of KP1 expression
      by some subsets of NHLs remains to be elucidated, its close association with B
      cell NHLs, mostly of the diffuse small cell type, should stimulate further
      pathologic and clinical investigations.

PMID- 7726139
TI  - Epithelial-myoepithelial carcinoma of salivary glands. A clinicopathologic, DNA
      flow cytometric, and immunohistochemical study of Ki-67 and HER-2/neu oncogene.
AB  - Thirty-one salivary gland epithelial-myoepithelial carcinomas from 26 patients
      were studied by DNA flow cytometry, and immunostaining for Ki-67 and HER-2/neu
      oncogene product. The results were correlated with clinicopathologic factors and
      patient outcome. The tumor most commonly involved the parotid gland, and mainly
      affected patients in their 6th to 8th decades. The clinical course was
      characterized by a high incidence of local recurrence (50%) and not infrequent
      distant metastasis (25%). None of the patients in this cohort died of disease.
      DNA content analysis revealed 21 neoplasms with DNA diploidy and 5 tumors with
      DNA aneuploidy; all aneuploid cases were near-diploid (hyperdiploidy) and showed
      low proliferative activity. All aneuploid and 60% of the diploid neoplasms
      developed recurrences and/or metastases. Immunohistochemical analysis of Ki-67
      proliferation markers also showed low overall growth fractions. Interestingly, Ki
      67 immunoreactivity was largely restricted to myoepithelial cells, suggesting a
      central role for this cell in the development of these tumors. HER-2/neu oncogene
      analysis failed to demonstrate overexpression in any of the tumors examined. This
      study indicates that epithelial-myoepithelial carcinoma is a low grade malignant
      neoplasm with a high propensity for recurrence. HER-2/neu oncogene and Ki-67
      offer no additional advantages over current factors in the biologic evaluation of
      these neoplasms. DNA aneuploidy may allow for the identification of a subset of
      tumors that is more prone to recurrence and metastasis, but further studies with
      extended follow-up are needed.

PMID- 7726140
TI  - The cytopathology of proliferative breast disease. Comparison with features of
      ductal carcinoma in situ.
AB  - Epithelial hyperplasia, a component of proliferative breast disease (PBD), is a
      known risk factor for the development of breast carcinoma. To determine if
      criteria established for tissue biopsy could be used to more precisely define
      cytologic criteria for diagnosis of PBD, 37 breast fine-needle aspirates with
      biopsy diagnoses of PBD were studied. In cases with adequate cellularity, the
      following findings were consistently observed: (1) three-dimensional cell
      clusters with outlying myoepithelial cells, swirling intralumenal masses and
      peripheral, slit-like, irregular sublumens (65% of cases); (2) convoluted sheets
      of ductal epithelium with outlying myoepithelial cells and bulbous projections
      tethered to the ductal lining (29%); and (3) a background of discohesive small
      frayed groups of ductal cells (32%). Of the 15 cases that did not meet these
      criteria, most were paucicellular (87%), which suggested sampling error. Other
      cytologic features that were observed included: moderately increased cellularity
      (20 cases), moderate-to-marked nuclear overlap (14 cases), minimal nuclear
      atypia, and few single epithelial cells. Fifteen cases of confirmed ductal
      carcinoma in situ were studied for comparison. In these cases, cellularity,
      nuclear overlap, and atypia were increased, but swirling intralumenal masses,
      prominent myoepithelial cells and slit-like lumens were absent. In conclusion,
      the features of PBD established for tissue biopsy can be applied to cytologic
      specimens, and may provide useful clues to the diagnosis of epithelial
      hyperplasia in breast fine-needle aspiration specimens.

PMID- 7726141
TI  - CD31 quantitative immunocytochemical assays in breast carcinomas. Correlation
      with current prognostic factors.
AB  - The distribution of PECAM-1/CD31 molecule was investigated in 133 breast
      carcinomas using monoclonal antibody and frozen sections. Anti-CD31 labels
      endothelial cells and reflects stromal angiogenesis. The CD31 immunoreactivity
      was evaluated by computer-assisted analysis of digitized microscopic images. The
      automatic screening of the whole preparation and the measurements of the mean
      CD31 immunostained surface was performed in each case. A similar procedure was
      achieved for p53, cathepsin D, P-gp, pHER-2/neu, Ki67, pS2 estrogen and
      progesterone antigenic sites immunodetection. The image analysis of positive CD31
      surface was variable, ranging from 4% to 33% (mean 14.7%, SD = 5.43). The CD31
      positive surface correlated (P < .01) with the Nottingham prognostic index, but
      not with the tumor size, the node status, the tumor grade, nor with the patient
      age. Also the CD31 immunoreactivity was independent of the pHER-2/neu, Ki67
      antigen, p53, ER, PR and pS2 immunodetectable expression in tumors, but
      correlates with that of cathepsin D (P = .024) and P-gp (P = .028), which
      reflects the multi-drug resistance capacity of tumor cells. In conclusion, CD31
      positive vessels assessed on frozen sections by image analysis constitute an
      excellent method of evaluating tumor stromal angiogenesis, and can be further
      used for clinical purposes. The results also suggest that the CD31/PECAM molecule
      may be involved in the spread of tumor by interacting with extracellular matrix
      lysis that results from the tumor cell proteasic activity and with multidrug
      resistance.

PMID- 7726142
TI  - Absence of Epstein-Barr virus in medullary carcinoma of the breast as
      demonstrated by immunophenotyping, in situ hybridization and polymerase chain
      reaction.
AB  - Medullary carcinoma of the breast is an epithelial malignant proliferation that
      shares many characteristics (macroscopic, microscopic, epidemiologic, and
      prognostic) with lymphoepithelioma-like carcinomas of various sites. The authors
      hypothesized that they could also share the same etiologic agent, the Epstein
      Barr virus (EBV). Epstein-Barr virus, a virus of the herpesvirus family, is to be
      associated with lymphoepithelioma-like carcinomas of the nasopharynx, stomach,
      lung, thymus, and salivary gland. Therefore, the authors looked for the virus in
      a series of 10 medullary carcinomas of the breast. Using immunohistochemistry, in
      situ hybridization and polymerase chain reaction, this investigation failed to
      show evidence of EBV. Similar negative results have been reported in
      lymphoepithelioma-like carcinomas arising in the skin and in the uterine cervix,
      which like the breast do not originate in the foregut. These results suggest that
      the pathogenesis of these tumors is not unique, implicating probably different
      etiopathogenic entities.

PMID- 7726143
TI  - Gastric carcinoma with osteoclast-like giant cells. Report of four cases.
AB  - Four cases of gastric carcinoma are described that are associated with an
      osteoclast-like giant cell (OGC) stromal component. The patients were all middle
      aged men (range 53-63 years). Microscopically, the tumors were characterized by a
      bland cytologic appearance, and an either solid or cribriform pattern. Osteoclast
      like giant cells were found adjacent to, or intimately intermixed with, the
      neoplastic cells in the primary gastric masses and in the lymph nodal metastases
      and were often associated with lymphocytes, histiocytes, and desmoplastic stroma.
      By immunohistochemistry, mononuclear cells and OGCs showed diffuse positivity for
      alpha-1-antichymotrypsin, alpha-1-antitrypsin, and CD68. Neoplastic cells that
      were positive for keratin and CEA, also showed reactivity for vimentin and the
      latent membrane protein of Epstein-Barr virus in one case. At follow-up, three
      patients had died at 13, 15, and 24 months after diagnosis, and one is still
      alive, without evidence of disease, after 120 months. This report describes a
      novel variant of gastric carcinoma with distinctive and histologic features.

PMID- 7726144
TI  - Neuromuscular choristoma.
AB  - Neuromuscular choristomas are rare, with only 13 cases having been previously
      reported. They usually arise in association with large nerves, and most often
      occur in the first decade of life. A few have been congenital. Although resection
      is typically curative, in two instances partial resection alone appears to have
      been followed by spontaneous regression. The authors report an unusual example of
      an otherwise classic neuromuscular choristoma where the lesion appeared to grow
      after incomplete initial resection. Re-excision disclosed a fibromatosis
      unassociated with choristoma. Despite its wide excision, a recurrence of the
      fibromatosis required a forequarter amputation. Theories of histogenesis and the
      clinicopathologic features of the neuromuscular choristomas reported to date are
      reviewed. The term "benign Triton tumor," although incorrectly applied to this
      lesion, should be reserved for benign, true nerve sheath neoplasms exhibiting
      myogenic differentiation.

PMID- 7726145
TI  - Inflammatory responses to biomaterials.
AB  - Implanted biomedical devices are of increasing importance in modern medical care.
      However, surprisingly little is known of the factors that determine
      biocompatibility of the materials used in these devices. These materials,
      although generally inert and non-toxic, can mediate a variety of adverse
      reactions, including inflammation, fibrosis, coagulation, and infection. This
      brief review focuses on the inflammatory responses (including fibrosis) that
      commonly occur around implanted biomaterials. Host proteins that spontaneously
      associate with implant surfaces are important determinants of the acute
      inflammatory response. In this regard, adsorbed fibrinogen appears particularly
      pro-inflammatory. Chronic inflammatory processes, in many cases in response to
      fragments of implanted biomaterials, may cause implant failure. In the case of
      silicone-filled mammary prostheses, the extravasation of silicone gel has been
      held responsible for a number of complications, including silicone granuloma,
      synovitis, connective-tissue disease, and lymphadenopathy. In some instances,
      material-mediated inflammatory responses may even cause degradation of the
      material itself (via oxidative products released by implant-associated
      inflammatory cells). Overall, there is insufficient knowledge of the determinants
      and mechanisms of host: implant responses. A clear understanding of
      tissue:biomaterial interactions will be required both to explain the pathogenesis
      of many implant-mediated complications and to aid in the development of more
      biocompatible materials for implantable devices.

PMID- 7726146
TI  - Comparison of cytogenetic analysis, southern analysis, and polymerase chain
      reaction for the detection of t(14; 18) in follicular lymphoma.
AB  - This study was undertaken to compare the ability of cytogenetic analysis (CG),
      Southern analysis (SA) and the polymerase chain reaction (PCR) to detect the
      t(14; 18) in follicular lymphoma (FL). All methodologies were performed by
      standard techniques. The probes used for SA included major breakpoint region
      (mbr) and minor cluster region (mcr) probes. The primers for PCR were identical
      or similar to those used by other investigators. One hundred fifteen cases of FL
      were ascertained by morphologic criteria, from which sufficient fresh tissue was
      available for both CG and molecular analysis. Eleven cases failed by both methods
      (nonrepresentative sampling). One hundred four cases showed evidence of an
      abnormal clone by CG and/or immunoglobulin gene rearrangement (IgH) studies.
      Cytogenetic analysis failed in 2 cases, was positive for t(14; 18) in 91 of the
      remaining 102 cases (89%) and detected a non-t(14; 18) close in 11 cases. An IgH
      clonal rearrangement was confirmed in all 104 cases. Southern analysis detected a
      mbr or mcr rearrangement in 78 of 104 cases (75%). Polymerase chain reaction
      detected an mbr or mcr rearrangement in 68 of 104 cases (65%). The use of PCR as
      a clinical test to detect t(14; 18)-positive lymphomas, with single primer sets
      for the mbr and mcr, will result in a high false-negative rate. The use of
      additional primers to detect uncommon breakpoints sites will be required to
      enhance the sensitivity of PCR for detection of t(14; 18) in malignant lymphoma.

PMID- 7726147
TI  - Hodgkin's disease associated with chronic lymphocytic leukemia. Eight additional
      cases, including two of the nodular lymphocyte predominant type.
AB  - Several reports of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma
      (SLL) and of coexisting or subsequent Hodgkin's disease (HD) have raised the
      question how these two disorders are related. The authors have identified eight
      new cases of B-cell low-grade lymphoproliferative disorders (LGLPD) and HD. Six
      of these cases were similar to those previously reported on by others in that the
      HD were mixed cellularity, nodular sclerosing, and lymphocyte depleted subtypes.
      The morphology in these cases was typical of HD, as was the immunohistochemical
      profile. However, the two remaining cases were notable in that the HD was of the
      nodular lymphocyte predominant type (NLPHD). To our knowledge, this association
      has not been well documented previously. In the two cases in this study, CLL and
      NLPHD were found simultaneously when each patient presented with lymphadenopathy
      and a lymphocytosis that was comprised of small monoclonal B lymphocytes
      coexpressing CD5. Lymph node biopsies in each case revealed typical NLPHD, with
      large, indistinct nodules containing scattered lymphocytic-histiocytic (L&H)
      cells. Focal, but distinct areas of CLL/SLL were also present. Immunostaining of
      the lymph node biopsy specimens showed the L&H cells to be CD20- and CD45
      positive, and to lack CD15 or evidence of light chain restriction. In one of
      these patients, a NLPHD-associated large cell lymphoma developed 8 months later.
      The large cells were CD20- and CD45 positive, with lambda light chain
      restriction. In contrast, the original CLL cells in this patient expressed kappa
      light chains. This report indicates that LGLPD can be associated with all
      subtypes of HD, including the NLP type. The discordant light chain restriction
      between the CLL and the NLPHD-associated large cell lymphoma in one of these
      cases indicates that the CLL and HD were probably not derived from the same
      clone.

PMID- 7726148
TI  - Extranodal lymphocyte predominance Hodgkin's disease. Clinical and pathologic
      features.
AB  - Although B-cell nodular lymphocyte predominance Hodgkin's disease (nodular
      paragranuloma, LPHD) typically presents at low stage, reported series have
      identified a minor population of patients with advanced disease.
      Clinicopathologic findings in 13 cases of LPHD are described that had extranodal
      manifestations. The B-cell immunophenotype was confirmed in all cases with
      paraffin-section immunostains. Nine patients presented with extranodal disease;
      distribution was in Waldeyer's ring (n = 2), spleen (n = 3), spleen and liver (n
      = 3), or bone marrow (n = 1). Three cases, clinically stage III/IV at
      presentation, had involvement of bone marrow (n = 2) or bone marrow, liver and
      spleen (n = 1) at relapse. One patient presented with clinical stage IIe disease
      and had involvement of spleen at relapse. Follow-up was available for 11 patients
      (range 4 months to 11 years; mean, 5 years). One patient died of disease and one
      died with disease because of therapeutic complications. Six patients were disease
      free and three had persistent or recurrent LPHD. Microscopically, LPHD was
      difficult to recognize in extranodal sites and could easily be mistaken for low
      grade non-Hodgkin's lymphoma or conventional Hodgkin's disease. Certain
      morphologic and immunophenotypic findings were effective in avoiding such
      diagnostic confusion. Thorough staging evaluation appears warranted for LPHD
      because it may be responsive to therapy, even in advanced stage or after relapse.
      Although LPHD is unexpected in extranodal samplings, the wary pathologist can
      suspect its presence on the basis of characteristic histopathologic features.
      Confirmation of the diagnosis may require paraffinsection immunostains.

PMID- 7726149
TI  - The H1 automated differential counter in determination of bone marrow remission
      in acute leukemia.
AB  - One hundred eighty-one bone marrow aspirates from 63 patients with acute leukemia
      were evaluated by the Technicon H1 automated differential counter and by
      microscopic examination for remission status after chemotherapy. Of the 163
      marrows that were conclusive by microscopic examination, 130 were in remission (<
      5% blast cells). This study focused on the following H1 alarms/flags to estimate
      their sensitivity for determination of remission: blast signal (BLSI), large
      unstained cells alarm (LUCA), baso blast alarm (BBLA), immature granulocytes
      (IGA) and atypia (ATYP). Basoblast alarm and BLSI revealed to be the most
      sensitive alarms (P < .0000 both), with 6 and 7 false-negative cases,
      respectively. Sensitivity, specificity, positive predictive value, negative
      predictive value and efficiency were: 79%, 92%, 70%, 94%, and 89%, respectively
      for BLSI, and 82%, 90%, 68%, 95%, and 88%, respectively for BBLA. Blast signal
      and BBLA did not turn up in 67 hematologically normal bone marrows. In
      conclusion, the H1, the baso channel in particular, is a sensitive and specific
      tool for estimation of bone marrow remission status in acute leukemia.

PMID- 7726150
TI  - Primary Ki-1 (anaplastic large cell) lymphoma of the brain and spinal cord.
AB  - The authors report a case of primary Ki-1 lymphoma of the brain. The patient was
      a 4 1/2-year-old black girl who presented with a 4- and 5-day history of
      headaches, nausea, vomiting, neck stiffness, and difficulty in walking. Computed
      tomography (CT) scan of the brain showed two discrete densities in the left
      occipital lobe and in the brain stem. Magnetic resonance imaging (MRI) showed
      multiple densities scattered over the brain surface and brain stem.
      Microscopically, the tumor was an anaplastic neoplasm that diffusely infiltrated
      brain parenchyma. The neoplastic cells were large with amphophilic cytoplasm,
      large nuclei with irregular nuclear contours and prominent nucleoli. A high
      mitotic rate including atypical mitotic figures was noted. Immunohistochemical
      stains showed diffuse strong positivity for CD30 and moderate focal staining for
      epithelial membrane antigen. Leukocyte common antigen, cytokeratin, neuron
      specific enolase, monocyte/macrophage and B- and T-marker stains were negative.
      The histology was characteristic for Ki-1 large cell lymphoma. Cytologic
      examination of cerebrospinal fluid (CSF) demonstrated similar neoplastic cells.
      This is one of the first reports of this variant in the pediatric population.

PMID- 7726151
TI  - Comparison of the clinical microscopy laboratory with the cytopathology
      laboratory in the detection of malignant cells in body fluids.

PMID- 7726152
TI  - Diffuse embryoma of the testis.

PMID- 7726153
TI  - Topics in protozoal diseases.

PMID- 7726154
TI  - Segregation patterns of a novel mutation in the mitochondrial tRNA glutamic acid
      gene associated with myopathy and diabetes mellitus.
AB  - We have identified a novel mtDNA mutation in a 29-year-old man with myopathy and
      diabetes mellitus. This T-->C transition at mtDNA position 14709 alters an
      evolutionarily conserved nucleotide in the region specifying for the anticodon
      loop of the mitochondrial tRNA(Glu). The nt-14709 mutation was heteroplasmic but
      present at very high levels in the patient's muscle, white blood cells (WBCs),
      and hair follicles; lower proportions of mutated mtDNA were observed in WBCs and
      hair follicles of all examined maternal relatives. In the patient's muscle,
      abnormal fibers showed mitochondrial proliferation, severe focal defects in
      cytochrome c oxidase activity, and absence of cross-reacting material for
      mitochondrially synthesized polypeptides. These fibers had higher levels of
      mutated mtDNA than did surrounding "normal" fibers. Although the percentage of
      mutated mtDNA in WBCs from family members were distributed around the percentage
      observed in the mothers, the pattern was different in hair follicles, where the
      mutated population tended to increase in subsequent generations. PCR/RFLP
      analysis of single hairs showed that the intercellular variations in the
      percentage of mutated mtDNA differed among family members, with younger
      generations having a more homogeneous distribution of mutated mtDNA in different
      hair follicles. These results suggest that the intercellular distribution of the
      mutated and wild-type mtDNA populations may drift toward homogeneity in
      subsequent generations.

PMID- 7726155
TI  - Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus:
      different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid
      mutation.
AB  - We report the clinical, biochemical, and molecular genetic findings in a family
      with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA
      glutamic acid mutation at position 14709. The proband and his sister presented
      with congenital myopathy and mental retardation and subsequently developed
      cerebellar ataxia. Other family members had either adult-onset diabetes mellitus
      with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and
      cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies.
      Biochemical studies of muscle mitochondria showed reduced complex I and IV
      activities. The mtDNA mutation was heteroplasmic in blood and muscle in all
      matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures
      containing high proportions of mutant mtDNA exhibited impaired mitochondrial
      translation. These observations indicate that mtDNA tRNA point mutations should
      be considered in the differential diagnosis of congenital myopathy. In addition
      they illustrate the diversity of phenotypes associated with this mutation in the
      same family and further highlight the association between mtDNA mutations and
      diabetes mellitus.

PMID- 7726156
TI  - Characterization of phenylalanine hydroxylase alleles in untreated
      phenylketonuria patients from Victoria, Australia: origin of alleles and
      haplotypes.
AB  - Mutations in the phenylalanine hydroxylase (PAH) gene were identified in a group
      of untreated phenylketonuria patients from Victoria, Australia. Ninety-eight
      percent of the alleles were identified, and a total of 26 different mutations
      were detected on 83 independent chromosomes. The three most prevalent mutations-
      R408W, I65T, and IVS12nt1--together accounted for 54% of the alleles. A number of
      alleles were demonstrated, by genealogical studies, to be of Irish or Scottish
      origin, including a newly described mutation 1197/1198 del A. The distribution
      and relative frequencies of the more common alleles in this population parallel
      observed frequencies in the British Isles and are consistent with the known
      history of Caucasian settlement of this region of Australia. We have analyzed the
      haplotype and polymorphic short tandem-repeat allele of the mutant chromosomes
      and describe a number of new associations.

PMID- 7726157
TI  - An atypical case of fragile X syndrome caused by a deletion that includes the
      FMR1 gene.
AB  - Fragile X syndrome is the most common form of inherited mental retardation and
      results from the transcriptional inactivation of the FMR1 gene. In the vast
      majority of cases, this is caused by the expansion of an unstable CGG repeat in
      the first exon of the FMR1 gene. We describe here a phenotypically atypical case
      of fragile X syndrome, caused by a deletion that includes the entire FMR1 gene
      and > or = 9.0 Mb of flanking DNA. The proband, RK, was a 6-year-old mentally
      retarded male with obesity and anal atresia. A diagnosis of fragile X syndrome
      was established by the failure of RK's DNA to hybridize to a 558-bp PstI-XhoI
      fragment (pfxa3) specific for the 5'-end of the FMR1 gene. The analysis of
      flanking markers in the interval from Xq26.3-q28 indicated a deletion extending
      from between 160-500 kb distal and 9.0 Mb proximal to the FMR1 gene. High
      resolution chromosome banding confirmed a deletion with breakpoints in Xq26.3 and
      Xq27.3. This deletion was maternally transmitted and arose as a new mutation on
      the grandpaternal X chromosome. The maternal transmission of the deletion was
      confirmed by FISH using a 34-kb cosmid (c31.4) containing most of the FMR1 gene.
      These results indicated that RK carried a deletion of the FMR1 region with the
      most proximal breakpoint described to date. This patient's unusual clinical
      presentation may indicate the presence of genes located in the deleted interval
      proximal to the FMR1 locus that are able to modify the fragile X syndrome
      phenotype.

PMID- 7726158
TI  - Seven novel mutations in the methylenetetrahydrofolate reductase gene and
      genotype/phenotype correlations in severe methylenetetrahydrofolate reductase
      deficiency.
AB  - 5-Methyltetrahydrofolate, the major form of folate in plasma, is a carbon donor
      for the remethylation of homocysteine to methionine. This form of folate is
      generated from 5,10-methylenetetrahydrofolate through the action of 5,10
      methylenetetrahydrofolate reductase (MTHFR), a cytosolic flavoprotein. Patients
      with an autosomal recessive severe deficiency of MTHFR have homocystinuria and a
      wide range of neurological and vascular disturbances. We have recently described
      the isolation of a cDNA for MTHFR and the identification of two mutations in
      patients with severe MTHFR deficiency. We report here the characterization of
      seven novel mutations in this gene: six missense mutations and a 5' splice-site
      defect that activates a cryptic splice site in the coding sequence. We also
      present a preliminary analysis of the relationship between genotype and phenotype
      for all nine mutations identified thus far in this gene. A nonsense mutation and
      two missense mutations (proline to leucine and threonine to methionine) in the
      homozygous state are associated with extremely low activity (0%-3%) and onset of
      symptoms within the 1st year of age. Other missense mutations (arginine to
      cysteine and arginine to glutamine) are associated with higher enzyme activity
      and later onset of symptoms.

PMID- 7726159
TI  - Seven new mutations in hMSH2, an HNPCC gene, identified by denaturing gradient
      gel electrophoresis.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is a relatively common
      autosomal dominant cancer-susceptibility condition. The recent isolation of the
      DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) responsible for HNPCC
      has allowed the search for germ-line mutations in affected individuals. In this
      study we used denaturing gradient-gel electrophoresis to screen for mutations in
      the hMSH2 gene. Analysis of all the 16 exons of hMSH2, in 34 unrelated HNPCC
      kindreds, has revealed seven novel pathogenic germ-line mutations resulting in
      stop codons either directly or through frameshifts. Additionally, nucleotide
      substitutions giving rise to one missense, two silent, and one useful
      polymorphism have been identified. The proportion of families in which hMSH2
      mutations were found is 21%. Although the spectrum of mutations spread at the
      hMSH2 gene among HNPCC patients appears extremely heterogeneous, we were not able
      to establish any correlation between the site of the individual mutations and the
      corresponding tumor spectrum. Our results indicate that, given the genomic size
      and organization of the hMSH2 gene and the heterogeneity of its mutation
      spectrum, a rapid and efficient mutation detection procedure is necessary for
      routine molecular diagnosis and presymptomatic detection of the disease in a
      clinical setup.

PMID- 7726160
TI  - De novo myotonic dystrophy mutation in a Nigerian kindred.
AB  - An expansion of an unstable (CTG)n trinucleotide repeat in the 3' UTR of a gene
      encoding a putative serine/threonine protein kinase (DMPK) on human chromosome
      19q13.3 has been shown to be specific for the myotonic dystrophy (DM) disease
      phenotype. In addition, a single haplotype composed of nine alleles within and
      flanking DMPK over a physical distance of 30 kb has been shown to be in complete
      linkage disequilibrium with DM. This has led to two hypotheses: (1)
      predisposition for (CTG)n instability results from a founder effect that occurred
      only once or a few times in human evolution; and (2) elements within the disease
      haplotype may predispose the (CTG)n repeat to instability. A detailed haplotype
      analysis of the DM region was conducted on a Nigerian (Yoruba) DM family, the
      only indigenous sub-Saharan DM case reported to date. Each affected member of
      this family had an expanded (CTG)n repeat in one of his or her DMPK alleles.
      However, unlike all other DM populations studied thus far, disassociation of the
      (CTG)n repeat expansion from other alleles of the putative predisposing haplotype
      was found. We conclude that the expanded (CTG)n repeat in this family is the
      result of an independent mutational event. Consequently, the origin of DM is
      unlikely to be a single mutational event, and the hypothesis that a single
      ancestral haplotype predisposes to repeat expansion is not compelling.

PMID- 7726161
TI  - Mutations in the human Ca(2+)-sensing-receptor gene that cause familial
      hypocalciuric hypercalcemia.
AB  - We report five novel mutations in the human Ca(2+)-sensing-receptor gene that
      cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe
      hyperparathyroidism. Each gene defect is a missense mutation (228Arg-->Gln,
      139Thr-->Met, 144Gly-->Glu, 63Arg-->Met, and 67Arg-->Cys) that encodes a
      nonconservative amino acid alteration. These mutations are each predicted to be
      in the Ca(2+)-sensing receptor's large extracellular domain. In three families
      with FHH linked to the Ca(2+)-sensing-receptor gene on chromosome 3 and in
      unrelated individuals probands with FHH, mutations were not detected in protein
      coding sequences. On the basis of these data and previous analyses, we suggest
      that there are a wide range of mutations that cause FHH. Mutations that perturb
      the structure and function of the extracellular or transmembrane domains of the
      receptor and those that affect noncoding sequences of the Ca(2+)-sensing-receptor
      gene can cause FHH.

PMID- 7726162
TI  - Testing parental imprinting in insulin-dependent diabetes mellitus by the marker
      association-segregation-chi 2 method.
AB  - Among patients with insulin-dependent diabetes mellitus (IDDM), an excess of DR3
      and DR4 alleles is classically described when compared with the general
      population. In addition, an excess of maternal DR3 and paternal DR4 alleles among
      patients (DR3DR4) is observed. In order to explain these observations, two
      alternative hypotheses can be tested: maternal effect and parental imprinting.
      Maternal effect has been tested and not rejected on a sample of 416 caucasians
      affected with IDDM. Under this hypothesis, the children of a DR3 mother are
      expected to have an earlier exposure and, hence, an earlier age at onset.
      However, we did not observe such a difference in age at onset in this data set.
      Using the marker-association-segregation-chi 2 method, we have tested four
      hypotheses with different parental effects of two susceptibility alleles, alpha 0
      and beta 0, at two different closely linked loci. Under the hypothesis that best
      fitted the data, the probability of being affected depended on the parental
      inheritance of the susceptibility alleles, suggesting parental imprinting (i.e.,
      differential role of maternal and paternal allele), without evidence for a cis
      trans effect. We conclude that parental imprinting on a specific allelic
      combination may explain the observations on the HLA genotypes of the patients and
      their relatives.

PMID- 7726163
TI  - Random search for shared chromosomal regions in four affected individuals: the
      assignment of a new hereditary ataxia locus.
AB  - Infantile-onset spinocerebellar ataxia (IOSCA) is an autosomal recessively
      inherited progressive neurological disorder of unknown etiology. This ataxia,
      identified so far only in the genetically isolated Finnish population, does not
      share gene locus with any of the previously identified hereditary ataxias, and a
      random mapping approach was adopted to assign the IOSCA locus. Based on the
      assumption of one founder mutation, a primary screening of the genome was
      performed using samples from just four affected individuals in two consanguineous
      pedigrees. The identification of a shared chromosomal region in these four
      patients provided the first evidence that the IOSCA gene locus is on chromosome
      10q23.3-q24.1, which was confirmed by conventional linkage analysis in the
      complete family material. Strong linkage disequilibrium observed between IOSCA
      and the linked markers was utilized to define accurately the critical chromosomal
      region. The results showed the power of linkage disequilibrium in the locus
      assignment of diseases with very limited family materials.

PMID- 7726164
TI  - The gene for hereditary bullous dystrophy, X-linked macular type, maps to the
      Xq27.3-qter region.
AB  - Bullous dystrophy, hereditary macular type (McKusick 302000), is an X-linked
      disorder and was originally described in a single kindred in the Netherlands by
      Mendes da Costa and Van der Valk in 1908. To determine the location of the
      bullous dystrophy gene, segregation studies were performed in this family and in
      a recently described Italian family. Using informative polymorphic markers, the
      gene could initially be localized on the Xq27-q28 region. No recombinants were
      noted with loci in Xq27.3-q28. Fine mapping places the bullous dystrophy locus
      distal to DXS102 (Xq26.3) in the Italian family and distal to DXS998 (Xq27.3) in
      the Dutch family.

PMID- 7726167
TI  - Ataxia with vitamin E deficiency: refinement of genetic localization and analysis
      of linkage disequilibrium by using new markers in 14 families.
AB  - Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease
      characterized clinically by neurological symptoms with often striking resemblance
      to those of Friedreich ataxia. This disorder has been reported previously as
      familial isolated vitamin E deficiency. We have mapped recently the AVED locus to
      a 5-cM confidence interval on chromosome 8q by homozygosity mapping in six
      Mediterranean families. We have now analyzed six new and two previously described
      families and demonstrate genetic homogeneity despite important clinical
      variability and wide geographic origins. Analysis of nine new tightly linked
      microsatellite markers, including four characterized in this study, revealed a
      predominant but not unique mutation in northern African populations, where this
      condition is more frequent. Haplotype analysis but also classical recombinations
      allowed us to refine the AVED position to a 1-cM interval. A YAC contig over this
      interval was constructed from marker STSs and YAC fingerprint data, in order to
      facilitate the search of the AVED gene.

PMID- 7726165
TI  - The severe perinatal form of autosomal recessive polycystic kidney disease maps
      to chromosome 6p21.1-p12: implications for genetic counseling.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is a one of the most common
      hereditary renal cystic diseases in children. Its clinical spectrum is widely
      variable with most cases presenting in infancy. Most affected neonates die within
      the first few hours of life. At present, prenatal diagnosis relies on fetal
      sonography, which is often imprecise in detecting even the severe form of the
      disease. Recently, in a cohort of families with mostly milder ARPKD phenotypes,
      an ARPKD locus was mapped to a 13-cM region of chromosome 6p21-cen. To determine
      whether severe perinatal ARPKD also maps to chromosome 6p, we have analyzed the
      segregation of seven microsatellite markers from the ARPKD interval in 22
      families with the severe phenotype. In the majority of the affected infants,
      ARPKD was documented by histopathology. Our data confirm linkage and refine the
      ARPKD region to a 3.8-cM interval, delimited by the markers
      D6S465/D6S427/D6S436/D6S272 and D6S466. Taken together, these results suggest
      that, despite the wide variability in clinical phenotypes, there is a single
      ARPKD gene. These linkage data and the absence of genetic heterogeneity in all
      families tested to date have important implications for DNA-based prenatal
      diagnoses as well as for the isolation of the ARPKD gene.

PMID- 7726166
TI  - Myotubular myopathy in a girl with a deletion at Xq27-q28 and unbalanced X
      inactivation assigns the MTM1 gene to a 600-kb region.
AB  - A young girl with a clinically moderate form of myotubular myopathy was found to
      carry a cytogenetically detectable deletion in Xq27-q28. The deletion had
      occurred de novo on the paternal X chromosome. It encompasses the fragile X
      (FRAXA) and Hunter syndrome (IDS) loci, and the DXS304 and DXS455 markers, in
      Xq27.3 and proximal Xq28. Other loci from the proximal half of Xq28 (DXS49,
      DXS256, DXS258, DXS305, and DXS497) were found intact. As the X-linked myotubular
      myopathy locus (MTM1) was previously mapped to Xq28 by linkage analysis, the
      present observation suggested that MTM1 is included in the deletion. However, a
      significant clinical phenotype is unexpected in a female MTM1 carrier. Analysis
      of inactive X-specific methylation at the androgen receptor gene showed that the
      deleted X chromosome was active in approximately 80% of leukocytes. Such
      unbalanced inactivation may account for the moderate MTM1 phenotype and for the
      mental retardation that later developed in the patient. This observation is
      discussed in relation to the hypothesis that a locus modulating X inactivation
      may lie in the region. Comparison of this deletion with that carried by a male
      patient with a severe Hunter syndrome phenotype but no myotubular myopathy, in
      light of recent linkage data on recombinant MTM1 families, led to a considerable
      refinement of the position of the MTM1 locus, to a region of approximately 600
      kb, between DXS304 and DXS497.

PMID- 7726168
TI  - Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and
      loss of heterozygosity for EXT-linked markers on chromosomes II and 8.
AB  - Hereditary multiple exostosis (EXT) is an autosomal dominant disorder
      characterized by bony exostoses at the ends of the long bones. Linkage studies
      have recently suggested that there are three chromosomal locations for EXT genes,
      8q24.1 (EXT1), the pericentric region of 11 (EXT2), and 19p (EXT3). As part of a
      larger study to determine the frequencies of the three EXT types in the United
      States, we have ascertained a large multigenerational family with EXT and one
      family member with a chondrosarcoma. This family demonstrated linkage of the
      disease to chromosome 11 markers. The constitutional and tumor DNAs from the
      affected family member were compared using short-tandem-repeat markers from
      chromosomes 8, 11, and 19. Loss of heterozygosity (LOH) in the tumor was observed
      for chromosome 8 and 11 markers, but chromosome 19 markers were intact. An
      apparent deletion of the marker D11S903 was observed in constitutional DNA from
      all affected individuals and in the tumor sample. These results indicate that the
      EXT2 gene maps to the region containing marker D11S903, which is flanked by
      markers D11S1355 and D11S1361. Additional constitutional and chondrosarcoma DNA
      pairs from six unrelated individuals, two of whom had EXT, were similarly
      analyzed. One tumor from an individual with EXT demonstrated LOH for chromosome 8
      markers, and a person with a sporadic chondrosarcoma was found to have tumor
      specific LOH and a homozygous deletion of chromosome 11 markers. These findings
      suggest that EXT genes may be tumor-suppressor genes and that the initiation of
      tumor development may follow a multistep model.

PMID- 7726169
TI  - Loss of heterozygosity in chondrosarcomas for markers linked to hereditary
      multiple exostoses loci on chromosomes 8 and 11.
AB  - Hereditary multiple exostoses (EXT; MIM 133700) is an autosomal dominant
      condition characterized by growth of multiple benign cartilage-capped tumors. EXT
      greatly increases the relative risk to develop chondrosarcoma, although most
      chondrosarcomas are sporadic. This observation suggests that, like the genes
      responsible for retinoblastoma and other dominantly inherited cancer
      susceptibility disorders, the genes that cause EXT may have tumor-suppressor
      function and may play a role in the pathogenesis of the related sporadic tumors.
      To investigate this hypothesis, we evaluated chondrosarcomas for loss of
      constitutional heterozygosity (LOH) at polymorphic loci linked to three recently
      identified genomic regions containing genes involved in EXT. LOH for markers
      linked to EXT1 on chromosome 8 was detected in a chondrosarcoma that arose in a
      man with EXT. Four of 17 sporadic tumors showed LOH for markers linked to EXT1,
      and 7 showed LOH for markers linked to EXT2 on chromosome 11. In all, LOH was
      observed for markers linked to EXT1 or EXT2 in 44% of the 18 tumors, whereas
      heterozygosity was retained for markers on 19p linked to EXT3. These findings
      support the hypothesis that genes on 8q and the pericentromeric region of 11 have
      tumor-suppressor function and play a role in the development of chondrosarcomas.

PMID- 7726170
TI  - Wilson disease in Iceland: a clinical and genetic study.
AB  - A survey of Wilson disease in Iceland has revealed two large kindreds with
      affected individuals. We have carried out studies of haplotypes of dinucleotide
      repeat polymorphisms (CA repeats) flanking the Wilson disease gene. The same
      mutation, a 7-bp deletion, is present in both families, and the clinical features
      are similar. The haplotype data and nature of the mutation support the existence
      of a founder chromosome carrying the mutation. This Icelandic mutation was not
      found in patients of Irish or Scottish origins, who could share some of the
      Icelandic ancestral genes. Although the protein function is predicted to be
      completely abolished by the deletion, predicting early-onset liver disease, we
      find that the patients present with later-onset neurological and psychiatric
      symptoms. We show that alternative splicing of the transcript in the region of
      the deletion could contribute to later onset, suggesting that alternative
      isoforms of the protein might have some functional significance.

PMID- 7726171
TI  - The fragile X premutation in carriers and its effect on mutation size in
      offspring.
AB  - The pattern of inheritance in the fragile X (fra(X)) mutation follows a
      multistage intergenerational process in which the premutation evolves into the
      full mutation and the characteristic phenotype of the fra(X) syndrome after
      passing through oogenesis or a postzygotic event. Findings from our multicenter
      study confirm a strong direct relationship between fra(X) premutation size in the
      mother and probability of a full mutation in offspring with the mutation.
      Remarkably, the best-fitting equations are nonlinear asymptotic functions. The
      close approximation to both the logistic model and Gompertz suggests a process of
      accumulation of errors in DNA synthesis, as has been proposed previously. We also
      note that a larger-than-expected number of daughters of transmitting males have
      premutations that are smaller than their fathers', and that proportion is
      significantly higher than the proportion of daughters whose premutations are
      smaller than their mothers'. Intergenerational decreases in premutation size have
      been reported in other trinucleotide-repeat disorders and also appear to be
      parent-of-origin specific. Thus, while intergenerational expansion to the full
      mutation in fra(X) may manifest a postzygotic event, decreases in mutation size
      may occur during or prior to meiosis.

PMID- 7726172
TI  - Deletions of the elastin gene at 7q11.23 occur in approximately 90% of patients
      with Williams syndrome.
AB  - To investigate the frequency of deletions of the elastin gene in patients with
      Williams syndrome (WS), we screened 44 patients by both FISH and PCR
      amplification of a dinucleotide repeat polymorphism. FISH was performed using
      cosmids containing either the 5' or the 3' end of the elastin gene. PCR analysis
      was performed on the patients and their parents with a (CA)n repeat polymorphism
      found in intron 17 of the elastin locus. Of the 44 patients screened, 91% were
      shown to be deleted by FISH. Using the DNA polymorphism, both maternally (39%)
      and paternally (61%) derived deletions were found. Four patients were not deleted
      for elastin but have clinical features of WS. Since deletions of elastin cannot
      account for several features found in WS, these patients will be valuable in
      further delineation of the critical region responsible for the WS phenotype.
      Although PCR can be useful for determining the parental origin of the deletion,
      our results demonstrate that FISH analysis of the elastin locus provides a more
      rapid and informative test to confirm a clinical diagnosis of WS. The presence of
      two copies of the elastin locus in a patient does not, however, rule out WS as a
      diagnosis.

PMID- 7726173
TI  - Molecular definition of deletions of different segments of distal 5p that result
      in distinct phenotypic features.
AB  - Cri du chat syndrome (CDC) is a segmental aneusomy associated with deletions of
      chromosome 5p15. In an effort to define regions that produce the phenotypes
      associated with CDC, we have analyzed deletions from 17 patients. The majority of
      these patients had atypical CDC features or were asymptomatic. Using these
      patients, we have mapped several phenotypes associated with deletions of 5p,
      including speech delay, catlike cry, newborn facial dysmorphism, and adult facial
      dysmorphism. This phenotypic map should provide a framework with which to begin
      identification of genes associated with various phenotypic features associated
      with deletions of distal 5p. We have also analyzed the parental origin of the de
      novo deletions, to determine if genomic imprinting could be occurring in this
      region. In addition, we have isolated cosmids that could be useful for both
      prenatal and postnatal assessments of del5(p) individuals.

PMID- 7726174
TI  - Homozygosity for Waardenburg syndrome.
AB  - In a large kindred including many individuals affected with Waardenburg (WS) type
      1 (WS1) syndrome, a child affected with a very severe form of WS type 3 was born.
      This child presented with dystopia canthorum, partial albinism, and very severe
      upper-limb defects. His parents were first cousins, both affected with a mild
      form of WS1. Molecular analysis of PAX3, the gene that was determined by linkage
      to cause the disorder in the family, demonstrated a novel missense mutation
      (S84F) in exon 2 of PAX3 within the paired box. While individuals affected with
      WS1 were heterozygous for the mutation, the child with WS3 was homozygous for
      S84F. The observation that the PAX3 homozygote in humans may allow life at least
      in early infancy and does not cause neural tube defects was unexpected, since, in
      all the mutations known in mice (splotch), homozygosity has led to severe neural
      tube defects and intrauterine or neonatal death.

PMID- 7726175
TI  - The genetic epidemiology of leprosy in a Brazilian population.
AB  - Data on leprosy patients have been obtained from the Dispensary of Leprosy of
      Campinas, Sao Paulo, where records on practically all cases of leprosy in the
      Campinas area during the period 1960-70 are filed. The whole sample comprises
      10,886 individuals, distributed among 1,568 families. Complex segregation
      analysis was utilized to determine the nature of the genetic factors that may
      operate on leprosy and its subtypes. The results suggest the presence of a
      recessive major gene controlling susceptibility to leprosy per se, with frequency
      of approximately .05, although there are deviations from the expected Mendelian
      segregation proportions. Possible etiologic heterogeneity was examined by
      considering two subtypes separately: for lepromatous leprosy and tuberculoid
      leprosy there are suggestions for a segregating major effect; however, Mendelian
      transmission could not be demonstrated in either case. Therefore, there is no
      evidence to suggest unique genetic determinants for leprosy subtypes.

PMID- 7726176
TI  - Differential allelic expression of the type II collagen gene (COL2A1) in
      osteoarthritic cartilage.
AB  - Osteoarthritis (OA) is a common debilitating disease resulting from the
      degeneration of articular cartilage. The major protein of cartilage is type II
      collagen, which is encoded by the COL2A1 gene. Mutations at this locus have been
      discovered in several individuals with inherited disorders of cartilage. We have
      identified 27 primary OA patients who are heterozygous for sequence dimorphisms
      located in the coding region of COL2A1. These dimorphisms were used to
      distinguish the mRNA output from each of the two COL2A1 alleles in articular
      cartilage obtained from each patient. Three patients demonstrated differential
      allelic expression and produced < 12% of the normal level of mRNA from one of
      their COL2A1 alleles. The same allele shows reduced expression in all three
      patients, and this allele is more frequent in a well-defined OA population than
      in a control group, suggesting the possible existence of a rare COL2A1 allele
      that predisposes to OA.

PMID- 7726177
TI  - Genetic and environmental sources of fibrinogen variability in Israeli families:
      the Kibbutzim Family Study.
AB  - Genetic and environmental determinants of plasma fibrinogen were investigated in
      a sample of 82 kindreds residing in kibbutz settlements in Israel. The sample
      included 223 males and 229 females ages 15-97 years. Fibrinogen levels were first
      adjusted for variability in sex and age. There was a significant familial
      aggregation of adjusted fibrinogen levels, as indicated by inter- and intraclass
      correlation coefficients significantly different from zero. Commingling analysis
      implied that in this population a mixture of two normal distributions fit the
      adjusted fibrinogen levels better than did a single normal distribution. Complex
      segregation analysis was first applied to these sex- and age-adjusted data.
      Heterogeneous etiologies for individual differences were suggested. There was
      evidence for a nontransmitted environmental major factor in addition to polygenic
      genes that explained the mixture of distributions. In parallel, a single
      recessive locus with a major effect that explained the adjusted variation in
      fibrinogen could not be rejected. However, when the regression model for sex and
      age allowed coefficients to be ousiotype (class)-specific, the recessive genetic
      model was rejected and the mixed environmental one was not. These results
      suggested that particular ousiotypes determined by the major environmental factor
      are associated with a steeper increase of fibrinogen with age. While at the age
      of 20 years, the major environmental factor contributed 10% to fibrinogen
      variability, and 48% was explained by polygenic loci, at 80 years of age, the
      major factor explained 64% and only approximately 20% was explained by polygenic
      factors.

PMID- 7726178
TI  - Segregation distortion in the offspring of Afro-American fathers with postaxial
      polydactyly.
AB  - The unclear pattern of inheritance of postaxial polydactyly prompted this search
      for evidence of imprinting or change of expression in males and females using
      material of the Latin American Collaborative Study of Congenital Malformations.
      The frequency of affected offspring for 196 fathers with polydactyly was compared
      with that for 233 mothers with the same condition, stratified according to
      African and non-African ancestry. The postaxial polydactyly prevalence rate among
      the offspring of affected black fathers (44%) was larger than that in the group
      of affected black mothers (31%), with no difference between affected nonblack
      fathers (34%) and affected nonblack mothers (33%). The sex ratio (.51) observed
      in 631 black propositi and in 829 nonblack propositi with polydactyly (.58) could
      be a further indication of etiologic heterogeneity for polydactyly between these
      two ethnic groups. The segregation distortion in favor of affected among the
      offspring of affected black fathers could be interpreted as the effect of a sex
      linked recessive modifier gene acting during gametogenesis on an autosomal
      dominant polydactyly gene, this modifier being more frequent in Africans.

PMID- 7726179
TI  - High-resolution genetic mapping of complex traits.
AB  - Positional cloning requires high-resolution genetic mapping. To plan a positional
      cloning project, one needs to know how many informative meioses will be required
      to narrow the search for a disease gene to an acceptably small region. For a
      simple Mendelian trait studied with linkage analysis, the answer is
      straightforward. In this paper, we address the situation of a complex trait
      studied with affected-relative-pair methods. We derive mathematical formulas for
      the size of an appropriate confidence region, as a function of the relative risk
      attributable to the gene. Using these results, we provide graphs showing the
      number of relative pairs required to narrow the gene hunt to an interval of a
      given size. For example, we show that localizing a gene to 1 cM requires a median
      of 200 sib pairs for a locus causing a fivefold increased risk to an offspring
      and 700 sib pairs for a locus causing a twofold increased risk. We discuss the
      implications of these results for the positional cloning of genes underlying
      complex traits.

PMID- 7726180
TI  - Multipoint interval mapping of quantitative trait loci, using sib pairs.
AB  - The sib-pair interval-mapping procedure of Fulker and Cardon is extended to take
      account of all available marker information on a chromosome simultaneously. The
      method provides a computationally fast multipoint analysis of sib-pair data,
      using a modified Haseman-Elston approach. It gives results very similar to those
      of the earlier interval-mapping procedure when marker information is relatively
      uniform and a coarse map is used. However, there is a substantial improvement
      over the original method when markers differ in information content and/or when a
      dense map is employed. The method is illustrated by using simulated sib-pair
      data.

PMID- 7726181
TI  - MtDNA haplogroups in Native Americans.

PMID- 7726182
TI  - A mitochondrial mutation at nt 9101 in the ATP synthase 6 gene associated with
      deficient oxidative phosphorylation in a family with Leber hereditary optic
      neuroretinopathy.

PMID- 7726183
TI  - Exclusion of chromosome 1q21-q31 from linkage to three pedigrees affected by the
      pigment-dispersion syndrome.

PMID- 7726184
TI  - Molecular analysis of glucose-6-phosphate dehydrogenase variants in the Solomon
      Islands.

PMID- 7726185
TI  - Race hygiene in Nazi Germany.

PMID- 7726186
TI  - Current status of laboratory diagnosis for Lyme disease.
AB  - Laboratory tests have been used extensively to help diagnose Borrelia burgdorferi
      infections. In many cases, results of indirect fluorescent antibody (IFA)
      staining methods or an enzyme-linked immunosorbent assay (ELISA), combined or
      separate from findings of Western blot analyses, have confirmed clinical
      diagnoses of Lyme disease. Alternative assays, such as culturing or DNA detection
      by polymerase chain reaction (PCR) methods, can provide more definitive evidence
      of B. burgdorferi infection than can antibody assays. However, aside from being
      more expensive, culturing B. burgdorferi from human tissues and fluids gives us a
      low yield, while results of PCR analyses can be as misleading as those obtained
      by performing IFA staining methods or an ELISA if there are false-negative or
      false-positive reactions. With increased knowledge of human immune responses to
      key proteins of B. burgdorferi, such as those with molecular masses of 21, 31,
      34, 39, 41, and 93 kilodaltons, Western blot analyses are being used more
      frequently to confirm B. burgdorferi infections. These methods have been
      particularly helpful in identifying false-positive reactions in an ELISA. Until
      highly sensitive and specific assays have been adequately standardized, diagnosis
      of Lyme disease should be based primarily on clinical and epidemiologic evidence.

PMID- 7726187
TI  - Erythema migrans and early Lyme disease.
AB  - Erythema migrans (EM) must be distinguished from other entities including
      streptococcal and staphylococcal cellulitis, hypersensitivity reactions to
      arthropod bites, plant dermatitis, tinea, and granuloma annulare. Although EM
      lesions may be pruritic or painful, these complaints are generally mild. Central
      clearing may be absent in > 50% of patients. Multiple lesions, formerly present
      in 50% of U.S. patients, now occur in approximately 20%. EM develops days to 1
      month after a tick bite (median 7-10 days), and lesion diameter increases with
      duration. Most patients have associated complaints, with fatigue (54%), myalgia
      (44%), arthralgia (44%), headache (42%), and fever and/or chills (39%) being the
      most common. Respiratory and gastrointestinal complaints are infrequent. Symptoms
      may begin prior to the onset of, concomitant with, or after resolution of the
      rash. The incidence of viral-like illness due to Lyme disease without EM is
      unknown. Antibodies to Borrelia burgdorferi are absent in up to 50% of patients
      at presentation, with initial seropositivity most likely in those with EM of
      longer duration. The vast majority of patients will become seropositive within
      the first month of illness, even with treatment. Although there is evidence that
      B. burgdorferi can spread to the blood and central nervous system soon after
      onset of infection, oral therapy is highly effective in preventing objective
      extracutaneous complications of Lyme disease. The most appropriate choice, route
      of administration, and duration of therapy require further study. Because of
      variations in the etiologic agent between North America and Europe, comparisons
      of disease manifestations, treatment, and prognosis of Lyme disease must be made
      cautiously.

PMID- 7726188
TI  - Environmental risk and prevention of Lyme disease.
AB  - An understanding of the environmental determinants of Lyme disease risk is
      essential to evaluate human disease potential and to recommend strategies for
      disease prevention. Tick vectors of Lyme disease require a vertebrate blood meal
      during each of three motile developmental stages (larva, nymph, and adult).
      Although the immature stages (larvae and nymphs) exhibit broad and overlapping
      host ranges, adult ticks are primarily dependent on deer for feeding and
      reproduction. Consequently, the distribution and abundance of these ticks often
      reflect those of deer. Several species of smaller mammals and some birds that
      host immature ticks are also competent reservoirs for Borrelia burgdorferi, which
      becomes established within the tick population during feeding. The relative
      abundance of these host species and their ability to infect ticks are key factors
      in determining the distribution of Lyme disease risk in the local environment.
      Available methods for reducing the risk of Lyme disease in the environment
      include the application of insecticides and use of deer fencing, which have been
      shown to be 83-97% effective in reducing risk. However, the adverse environmental
      impact of insecticides and high cost of deer fencing limit these methods to high
      risk areas where human exposure is constant and unavoidable (i.e., residential or
      occupational). Personal protection in high-risk areas can lessen the likelihood
      of contact with ticks. Future prevention methods may include host-targeted
      insecticides, environmental alteration, and biologic control. Moreover, research
      is currently directed to identifying antigens for use in recombinant human
      vaccines.

PMID- 7726189
TI  - Early disseminated Lyme disease: cardiac manifestations.
AB  - The cardiac features of Lyme disease usually occur within weeks to months of the
      infecting tick bite; the result may be disruption of the conduction system,
      leading to heart block and muscle dysfunction, causing a mild myopericarditis.
      Lyme carditis is usually mild, although permanent heart block and a few
      fatalities claimed to be due to Lyme carditis have been reported, the latter
      usually with poor documentation. In general, Lyme carditis is treatable and
      curable with antibiotic regimens in current use. Recent reports have suggested
      that Lyme disease may be a cause of chronic congestive cardiomyopathy. Lyme
      carditis should be considered in the proper clinical setting with appropriate use
      of diagnostic tests, recalling that patients with carditis early in Lyme disease
      may be seronegative and that all patients who are seropositive do not necessarily
      have Lyme disease.

PMID- 7726190
TI  - Early disseminated Lyme disease: Lyme meningitis.
AB  - Lyme meningitis is the direct result of invasion of the nervous system by
      Borrelia burgdorferi. Occurring within the first few months of infection, it
      initially presents as a chronic basilar meningitis. Much about the pathogenesis
      of Lyme meningitis has been learned from animal models, the best being the adult
      Rhesus macaque. Injection of these animals with a highly infective strain of B.
      burgdorferi has led to a very predictable course of events: erythema migrans
      within the first few weeks after injection, development of anti-B. burgdorferi
      antibody, detection of spirochetemia in weeks 3 and 4, and central nervous system
      (CNS) invasion within 1 month with cerebrospinal fluid (CSF) pleocytosis. In
      humans, facial palsy is the earliest clinical indicator. Headache and meningismus
      are symptoms of inflammation of the subarachnoid space. Severe fatigue and
      arthralgia are common extra-CNS symptoms. Culture is not generally useful for
      detecting or confirming Lyme meningitis. False-positive serologic tests may occur
      in patients with other infections, inflammatory processes, or malignancies.
      Immunoblotting will differentiate true-from false-positive antibody reactivity.
      Lack of a consistently positive serum antibody titer should make the diagnosis of
      Lyme meningitis suspect. Positive CSF antibody is almost universal in patients
      with Lyme meningitis. Polymerase chain reaction is a direct test that is highly
      specific and sensitive. The antibiotic treatment of choice is intravenous (i.v.)
      cephalosporins or penicillin for 2-3 weeks. If the clinical picture is anything
      less than absolutely classic, a lumbar puncture and Western blot of serum should
      be obtained in a seropositive patient before initiating intravenous antibiotic
      therapy. There is no role at this time for long-term (> 1 month) intravenous
      antibiotics. Nonsteroidal antiinflammatory agents can also be of benefit.

PMID- 7726191
TI  - Musculoskeletal manifestations of Lyme disease.
AB  - Musculoskeletal involvement, particularly arthritis, is a common feature of Lyme
      disease. Early in the illness, patients may experience migratory musculoskeletal
      pain in joints, bursae, tendons, muscle, or bone in one or a few locations at a
      time, frequently lasting only hours or days in a given location. Weeks to months
      later, after the development of a marked cellular and humoral immune response to
      the spirochete, untreated patients often have intermittent or chronic
      monoarticular or oligoarticular arthritis-primarily in large joints, especially
      the knee-during a period of several years. The diagnosis of Lyme arthritis is
      usually based on the presence of this characteristic clinical picture, exposure
      in an endemic area, and an elevated immunoglobulin G antibody response to
      Borrelia burgdorferi. In addition, spirochetal DNA can often be detected in joint
      fluid by polymerase chain reaction. Lyme arthritis can usually be treated
      successfully with 1-month courses of oral doxycycline or amoxicillin or with 2-
      to 4-week courses of intravenous ceftriaxone. However, patients with certain
      genetic and immune markers may have persistent arthritis, despite treatment with
      oral or intravenous antibiotics. B. burgdorferi may occasionally trigger
      fibromyalgia, a chronic pain syndrome with diffuse joint and muscle symptoms.
      This syndrome does not appear to respond to antibiotic therapy.

PMID- 7726192
TI  - Neuroborreliosis.
AB  - Lyme disease is a multisystem infectious disease with frequent nervous system
      involvement. It affects peripheral nerves, the meningeal lining of the central
      nervous system (CNS), and the CNS parenchyma, but the underlying pathophysiology
      remains unclear. Considerable data suggest that dividing Lyme neuroborreliosis
      into early and late disease stages, as has been done with syphilis--the other
      well-known spirochetosis that affects the nervous system--lacks pathophysiologic
      validity. Early CNS seeding has been demonstrated, however, and lymphocytic
      meningitis and facial paralysis tend to occur relatively early in infection,
      although radiculoneuropathy and cranial neuropathies may also occur later. Less
      fulminant forms of peripheral nerve or CNS involvement may present later in the
      disease course. Encephalomyelitis may occur early or late but is rare;
      encephalopathy is far more common and tends to occur in patients with evidence of
      systemic (but not necessarily CNS) Lyme disease. Diagnosis of CNS infection has
      been difficult, and most studies have relied on indirect methods. Demonstration
      of intrathecal production of anti-Borrelia burgdorferi antibodies provides the
      strongest evidence, but correction for the amount of peripheral blood
      immunoreactivity to B. burgdorferi that crosses the blood-brain barrier is
      essential. Newer technologies have been applied in an effort to improve detection
      of B. burgdorferi itself--polymerase chain reaction may provide a sensitive tool
      for organism detection to complement immunologic techniques. The optimal
      treatment regimen for Lyme disease has not been defined, but a course of
      ceftriaxone (2 g/day) or cefotaxime (6 g/day) for 3-4 weeks is commonly
      prescribed. Intravenous penicillin and oral doxycycline (200 mg/day) for 2 weeks
      have been used successfully to treat Lyme meningitis, but these results require
      confirmation.

PMID- 7726193
TI  - Ocular manifestations of Lyme disease.
AB  - Although ocular manifestations of Lyme disease have long been noted, they remain
      a rare feature of the disease. The spirochete invades the eye early and remains
      dormant, accounting for both early and late ocular manifestations. A nonspecific
      follicular conjunctivitis occurs in approximately 10% of patients with early Lyme
      disease. Keratitis occurs often within a few months of onset of disease and is
      characterized by nummular nonstaining opacities. Inflammatory syndromes, such as
      vitritis and uveitis, have been reported; in some cases, a vitreous tap is
      required for diagnosis. Neuro-ophthalmic manifestations include neuroretinitis,
      involvement of multiple cranial nerves, optic atrophy, and disc edema. Seventh
      nerve paresis can lead to neurotrophic keratitis. In endemic areas, Lyme disease
      may be responsible for approximately 25% of new-onset Bell's palsy. Criteria for
      establishing that eye findings can be attributed to Lyme disease include the lack
      of evidence of other disease, other clinical findings consistent with Lyme
      disease, occurrence in patients living in an endemic area, positive serology,
      and, in most cases, response to treatment. Management of ocular manifestations
      often requires intravenous therapy.

PMID- 7726194
TI  - Muscle, reticuloendothelial, and late skin manifestations of Lyme disease.
AB  - In addition to classic organ system involvement, Lyme disease may be
      characterized by myositis, liver and spleen involvement, and atypical cutaneous
      manifestations. Myositis is characteristically localized near an involved joint
      or localized neuropathy. Nuclear imaging with gallium-67 may be useful for
      detection. Myositis responds to treatment with intravenous or oral antibiotics.
      Patients with erythema migrans have been observed to have liver function test
      abnormalities in the absence of symptomatic hepatitis. Splenomegaly has been
      noted infrequently in patients with Lyme disease. Chronic cutaneous
      manifestations of Lyme disease--including erythema migrans, acrodermatitis
      chronica atrophicans, and lymphadenosis benigna cutis--have been observed more
      frequently in Europe than in the United States. It appears that they are caused
      primarily by the Borrelia afzelii genomic group of Borrelia burgdorferi, which
      has been found exclusively in Europe.

PMID- 7726195
TI  - Lyme disease in children.
AB  - Lyme disease is the most common vector-borne disease among children in the United
      States; the incidence of Lyme disease is higher among children than among adults.
      Extensive publicity in the lay press about the effects of Lyme disease has led to
      widespread anxiety about this illness that is out of proportion to the actual
      frequency of severe consequences, especially among children. The problem is
      exacerbated by the difficulty of documenting the diagnosis (or more often of
      ruling out the diagnosis in children with vague symptoms), especially when the
      diagnosis depends on serologic tests that are often inaccurate. This caveat
      applies particularly to commercial laboratories using prepackaged kits, which
      often give inaccurate results that should not be relied on by themselves to make
      a diagnosis. Careful prospective studies have found that nearly 90% of children
      with Lyme disease have erythema migrans. Although there has been great concern
      about congenital Lyme disease, no data suggest that it is a significant problem,
      nor has transmission of Lyme disease through breast milk been documented.
      Virtually all children will respond well to treatment for any stage of Lyme
      disease. Misdiagnosis is the most common reason for treatment failure. Long-term
      follow-up studies indicate that the prognosis for children with Lyme disease is
      excellent.

PMID- 7726196
TI  - Anxiety and persistence of Lyme disease.
AB  - Lyme disease has become a major concern in endemic areas, in large measure
      because of fears that it does not respond to current antibiotic regimens. This
      anxiety has led to the use of untested drugs and longer courses of therapy than
      have been demonstrated to be necessary, with attendant increase in cost and
      toxicity. Concern about the lack of response to such therapy has convinced many
      patients that they have a permanent disease, with profound effects on their lives
      and those of their families. A better understanding of the natural history of
      Lyme disease and of possible causes for persisting symptoms other than active
      infection is needed to optimize management of such patients. Most symptoms
      persisting after adequate therapy can be explained by a small number of
      pathogenic mechanisms, only one of which is ongoing infection. Individualization
      of care and prudent analysis are crucial if overdiagnosis and overtreatment of
      Lyme disease are to be avoided.

PMID- 7726197
TI  - Priorities for neuropsychiatric genetics at the National Institutes of Health.
AB  - Over the last decade, molecular genetics has become one of the most important
      technologies in medical research. However, the application of these approaches to
      neuropsychiatric disorders has been met with both unreasonable expectations, and
      at times, unreasonable criticism. Molecular genetics has opened a new window into
      these disorders that has great promise, but is likely to reveal a complex
      reality. Clearly, the potential exists to actually define some of the disorders
      that make up the syndromes that we are studying. In doing so, we will not only
      begin to address the fundamental pathophysiology of these disorders, but also
      begin to design treatments based on this new understanding. In this report, a
      series of four papers on the genetics programs of the National Institutes of
      Health will be introduced.

PMID- 7726198
TI  - Psychiatric genetic research at the National Institute of Mental Health.
AB  - For some time it has been known through the results of family, twin, and adoption
      studies that heredity appears to play a significant causal role in many mental
      disorders, including schizophrenia, bipolar disorder, and other mood disorders,
      Alzheimer's Disease, panic disorder, obsessive compulsive disorder, autism,
      dyslexia, and Tourette's Syndrome. The precise patterns of inheritance of these
      complex disorders have not been determined, nor have the relevant genes been
      localized or cloned. Because the genetics are complex and because there is also
      clearly an environmental contribution to behavior, we expect the analysis of the
      genetics of mental illness to be arduous, and not quickly resolved. There are
      several compelling reasons to continue to focus our attention on uncovering the
      genetic factors for severe mental illness. Prominent among these are the
      implications for better treatment of mental disorders. The National Institute of
      Mental Health supports a wide range of studies on psychiatric genetic research.

PMID- 7726199
TI  - Human neuroscience at National Institute on Drug Abuse: implications for genetics
      research.
AB  - It is becoming clear that there is a genetic component to drug abuse. Family
      studies, adoption studies, and critical twin studies have all pointed to some
      genetic vulnerability or risk factors for an individual to abuse psychoactive
      drugs depending on certain psychopathologies in the biological parents and/or
      parents' own drug use. The question for the next generation of research at the
      National Institute on Drug Abuse (NIDA) is to apply the rapidly developing
      technology in molecular genetics in an effort to determine the candidate genes
      contributing to the risk.

PMID- 7726200
TI  - Genetic studies in alcohol research.
AB  - The National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports research
      to elucidate the specific genetic factors, now largely unknown, which underlie
      susceptibility to alcoholism and its medical complications (including fetal
      alcohol syndrome). Because of the genetic complexity and heterogeneity of
      alcoholism, identification of the multiple underlying factors will require the
      development of new study designs and methods of analysis of data from human
      families. While techniques of genetic analysis of animal behavioral traits (e.g.,
      targeted gene disruption, quantitative trait locus (QTL) mapping) are more
      powerful than those applicable to humans (e.g., linkage and allelic association
      studies), the validation of animal behaviors as models of aspects of human
      alcoholism has been problematic. Newly developed methods for mapping QTL
      influencing animal behavioral traits can not only permit analyses of human family
      data to be directly informed by the results of animal studies, but can also serve
      as a novel means of validating animal models of aspects of alcoholism.

PMID- 7726201
TI  - Research on neuropsychiatric genetics: interests of the National Institute of
      Neurological Disorders and Stroke.
AB  - The National Institute of Neurological Disorders and Stroke (NINDS) supports
      research concerning the determinants of normal and pathological development of
      the nervous system, from the genetic to the environmental. NINDS also funds basic
      and clinical research concerning the etiology, diagnosis, treatment,
      consequences, and prevention of the spectrum of neurodevelopmental disorders
      including neurobehavioral and neurodegenerative disorders (National Advisory
      Council Neurological Disorders and Stroke, 1989, 1992; Division of Convulsive,
      Developmental and Neuromuscular Disorders, NINDS, 1993).

PMID- 7726202
TI  - Genetic association study in psychiatry: analytical evaluation and a
      recommendation.
AB  - Recent analysis of the candidate gene, association study for psychiatric
      disorders have concluded that most statistically significant results are likely
      to be false positives because there are a large number of potential candidate
      loci and a low a priori probability that a given candidate locus will in fact be
      trait relevant. Hence, it was recommended that the alpha level (P level) be
      lowered for association studies. The present study demonstrates that lowering the
      alpha level to some fixed, predetermined value is not a recommended strategy.
      Rather, the probability of false positives (and false negatives) depends on such
      parameters as the prevalence of the disorder, the prevalence of the genotypes at
      the candidate locus, and the relative risk. In some areas of the parameter space,
      the adjustment to alpha may be modest. In other areas, however, even the
      requirement of one or more independent replications of the original results gives
      false positive rates exceeding 80% or 90%. Hence, the P levels required to
      minimize false positives may have to be changed from one statistical test to
      another even within the same study. A procedure for adjusting the probability
      level for a test of association between genotypes and a disorder is given.

PMID- 7726203
TI  - What association analysis can and cannot tell us about the genetics of complex
      disease.
AB  - Human genetics researchers have been intrigued for many years by weak-to-moderate
      associations between markers and diseases. However, in most cases of association,
      the cause of this phenomenon is still unknown. Recently, interest has grown in
      pursuing association studies for complex psychiatric diseases, either instead of
      or in addition to linkage studies. However, it is one thing to detect
      association; the next important step is to determine why. Here we consider what a
      disease-marker association in the weak-to-moderate range (relative risk < 5) can
      tell us about disease etiology. Two distinct models (not the only possibilities)
      which could explain such an association are formulated. One is a linkage
      disequilibrium or major disease gene model, involving tight linkage with a
      "necessary" major gene. The other is a pure association model, involving a
      "susceptibility" gene that has only a minor effect on disease state. It will be
      shown that association analysis cannot distinguish between these two models, and
      hence cannot elucidate the biological mechanism behind the association. (This
      statement holds for traditional population-based association tests, as well as
      for more recent family-based association tests.) The importance of drawing the
      distinction between these two genetic models and the implications for
      understanding the genetics of complex human disease will also be discussed.

PMID- 7726204
TI  - Candidate genes and association studies in psychiatry.

PMID- 7726205
TI  - Genetics of blood-injury fears and phobias: a population-based twin study.
AB  - Data on unreasonable fears of blood, needles, hospitals, and illness (BNHI) were
      collected by telephone interview from 541 MZ and 388 DZ pairs of female twins
      from the population-based Virginia Twin Registry. BNHI phobia was defined as the
      presence of fear accompanied by interference. Age at onset of phobia was found to
      be very similar to that of situational phobias previously assessed in the sample.
      Using a multiple threshold model, we found no evidence for qualitative
      differences between BNHI fears and BNHI phobia. The familial aggregation of fears
      appears to be entirely due to additive genetic variance. The possible exception
      to this is fear of illness, which, like BNHI phobias, seems to aggregate within
      families because of shared environmental factors. Although power to discriminate
      between the causes of familial resemblance is low, results suggest that random
      traumatic events and some social learning may be responsible for the onset of
      BNHI phobias. About two-thirds of variance is individual-specific environmental,
      and could include genotype x environment interaction and measurement error.

PMID- 7726206
TI  - Is cholinergic sensitivity a genetic marker for the affective disorders?
AB  - The recent literature on the involvement of cholinergic muscarinic mechanisms and
      adrenergic/cholinergic balance in affective disorders is reviewed and integrated
      with the older literature. There is strong evidence supporting the presence of
      exaggerated responses (behavioral, neuroendocrine, sleep) to cholinergic agents
      in affective disorder patients relative to normal controls and certain other
      psychiatric patients. There is also some, albeit less, conclusive evidence that
      these exaggerated responses may occur in euthymic individuals with a history of
      affective disorders, or in children at risk for development of affective
      disorders. Despite these promising results, suggesting a role for acetylcholine
      in the genetics of the affective disorders, further work in biochemistry and
      genetics is needed to link specific muscarinic receptors or other cholinergic
      variables to affective illness.

PMID- 7726207
TI  - Report from the Maryland Epidemiology Schizophrenia Linkage Study: no evidence
      for linkage between schizophrenia and a number of candidate and other genomic
      regions using a complex dominant model.
AB  - Our collaborative group has undertaken a linkage study of schizophrenia, using a
      systematic sample of patients admitted to Maryland hospitals. An initial sample
      of 39 families, each having two or more affecteds, was available for genotyping
      candidate genes, candidate regions, and highly polymorphic markers randomly
      distributed throughout the genome. We used a single complex dominant model (with
      a disease gene frequency of 0.005 and age-dependent penetrance for affected
      phenotype: for under 35, penetrance = .45; for 35 and older, penetrance = .85).
      We report here 130 markers, which met the exclusion criteria of LOD score < -2.00
      at theta > 0.01 in at least 10 informative families, and no evidence for
      heterogeneity. We also report here markers that were tested as candidates for
      linkage to the schizophrenic phenotype. They were selected based on the following
      criteria: a) proximity to reported chromosomal rearrangements (both 5q and 11q),
      b) suggestions of linkage from other families (5q), or c) presence of a candidate
      gene (5q, 11q, 3q: Dopamine receptors 1, 2, and 3, respectively). We also tested
      for mutations of codon 717 in exon 17 of the amyloid precursor protein (APP) gene
      and were unable to detect the C to T substitution in our schizophrenic group.

PMID- 7726208
TI  - Schizophrenia and mental retardation associated in a pedigree with retinitis
      pigmentosa and sensorineural deafness.
AB  - A family is presented with multiple cases of mild mental retardation,
      schizophrenia and other functional psychoses, progressive hearing loss, and
      retinitis pigmentosa (RP). It closely resembles a previously reported Finnish
      family. We suggest that the phenotypes are not associated in this family by
      chance, but define a novel syndrome which may be caused by a mutant allele at a
      single genetic locus.

PMID- 7726209
TI  - No allelic association between Parkinson's disease and dopamine D2, D3, and D4
      receptor gene polymorphisms.
AB  - Parkinson's disease is thought to be caused by a combination of unknown
      environmental, genetic, and degenerative factors. Evidence from necropsy brain
      samples and pharmacokinetics suggests involvement of dopamine receptors in the
      pathogenesis or pathophysiology of Parkinson's disease. Genetic association
      studies between Parkinson's disease and dopamine D2, D3 and D4 receptor gene
      polymorphisms were conducted. The polymorphism was examined in 71 patients with
      Parkinson's disease and 90 controls. There were no significant differences
      between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor
      loci. Our findings do not support the hypothesis that susceptibility to
      Parkinson's disease is associated with the dopamine receptor polymorphisms
      examined.

PMID- 7726210
TI  - Phenotypic definitions of psychotic illness for molecular genetic research.
AB  - New approaches to establish the molecular genetic bases of psychotic illness have
      recently been suggested which make different demands on diagnosticians attempting
      to provide reliable and valid phenotypic definitions. The diagnostic problems
      that have arisen to date and some solutions to these are considered. In addition,
      future diagnostic requirements for linkage and association studies are discussed.

PMID- 7726211
TI  - Study of the possible association of HLA class II, CD4, and CD3 polymorphisms
      with schizophrenia.
AB  - In the present study the HLA-DRB and DPB1 alleles as well as CD4 and CD3
      polymorphisms were tested in 100 Belgian schizophrenic patients and 204 controls.
      Our results indicate a significant negative association of the DPB1 0101 allele
      with schizophrenia (relative risk [RR] = 0.27). Furthermore a significant
      positive and negative association could be noticed for the CD4*A4 allele and
      CD4*A7/A8 genotype, respectively (RR 1.79 and 0.47, respectively). These findings
      suggest that some contribution of HLA class II and CD4 genes to an autoimmune
      like pathogenesis in schizophrenia might exist.

PMID- 7726212
TI  - Neurobehavioral characteristics of CGG amplification status in fragile X females.
AB  - Neurobehavioral correlates of CGG amplification were studied in 17 nonretarded
      adult female carriers of fragile X syndrome. The results revealed a significant
      relationship between IQ and the number of CGG repeats in the 5' untranslated
      region of the FMR1 gene. Women with a full mutation (> 200 CGG repeats) scored
      below average in IQ, visual-spatial perception, visual-spatial organization, and
      executive function. There were no differences in fine motor dexterity or memory
      as a function of CGG amplification status. A history of major depressive disorder
      was identified in 71% of the sample, but incidence of depression was not
      associated with the degree of CGG amplification. Schizotypal features were noted
      in 18%. No intellectual or neuropsychological deficit was found in women with a
      premutation (< 200 CGG repeats). Decrements in IQ, visual-spatial perception, and
      executive function appear to arise as a consequence of the CGG amplification.

PMID- 7726213
TI  - Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians:
      no association with schizophrenia.
AB  - Because antipsychotic drugs selectively block dopamine receptors and since
      dopamine D4 receptors are elevated sixfold in postmortem schizophrenia brain, we
      searched for possible abnormalities in the coding region of the genomic DNA
      sequence for the dopamine D4 receptor in control and schizophrenia tissues. The
      DNA sequence for the first 250 bases of exon 3 of this receptor was examined in
      the genomic DNA from 296 control individuals and 58 schizophrenics. Twenty-three
      out of 183 control blacks (12.6%) and 3 out of 24 (12.5%) schizophrenic blacks
      revealed a replacement of T by G, predicting a substitution of valine by glycine
      at amino acid position 194. The identical prevalence of 12.5% indicates that the
      variant is not associated with schizophrenia. The amino acid replacement occurs
      one amino acid away from a serine amino acid which is critical for the attachment
      of dopamine. None of the 147 Caucasians (113 controls; 34 schizophrenics)
      revealed this variant, termed D4GLYCINE194.

PMID- 7726214
TI  - Theory and practice of psychopharmacogenetics.
AB  - This article attempts to elucidate the theory and practice of
      psychopharmacogenetics. Eight working models were identified and characterized
      with a distinct view of risk factors in the host, the pathophysiology of disease,
      and the strategies for optimum therapy. The biochemical culprits related to
      adverse drug reaction in each case can be used to identify a risk and thus
      contribute to prevention research. Since the phenomenology of these uncommon
      conditions covers a broad spectrum of neuropsychiatric manifestations, the
      insights they generated might presage a better understanding of the natural
      history of a wider range of mental disorders associated with genetic
      vulnerability. The emerging information suggests that psychopharmacogenetics
      could be defined from clinical perspectives as multidimensional analysis of
      genes, drugs, and behaviour for the treatment and prevention of psychiatric
      disorders.

PMID- 7726215
TI  - Initial report of a genome search for the affective disorder predisposition gene
      in the old order Amish pedigrees: chromosomes 1 and 11.
AB  - Family data have suggested that some forms of major affective disorder are
      genetic. Certain of the Old Order Amish pedigrees have a familial form of the
      disease. In this report we present the results of genetic analyses under
      autosomal dominant mode of transmission with reduced penetrance and three
      different disease hierarchies. The pedigrees were genotyped with 28 markers from
      chromosome 1 and 23 markers from chromosomes 11. None of the markers result in a
      significantly positive lod score.

PMID- 7726216
TI  - Recent history of European psychiatry--ideas, developments, and personalities:
      the annual Eliot Slater Lecture.
AB  - Erik Stromgren had planned to revise and expand his Slater lecture to a more
      systematic and comprehensive paper for publication. Shortly before his death, he
      asked for the editorial opinion of one of us (IIG), but unfortunately he did not
      get the opportunity to complete his lecture manuscript. We find, however, that
      although kaleidoscopic and impressionistic, the manuscript, as it is, contains
      historic and autobiographical information of high value, which deserves a
      posthumous publication, for availability to a broader audience. His wife, Dr.
      Lizzie Sand Stromgren, has kindly released the manuscript, which here appears
      essentially as delivered at the Slater lecture in 1986, except for a few minor
      textual adaptions and the addition of a list of references (by A.B.).

PMID- 7726217
TI  - Linkage analysis of bipolar illness with X-chromosome DNA markers: a
      susceptibility gene in Xq27-q28 cannot be excluded.
AB  - Transmission studies have supported the presence of a susceptibility gene for
      bipolar (BP) illness on the X-chromosome. Initial linkage studies with color
      blindness (CB), glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the
      blood coagulation factor IX (F9) have suggested that a gene for BP illness is
      located in the Xq27-q28 region. We tested linkage with several DNA markers
      located in Xq27-q28 in 2 families, MAD3 and MAD4, that previously were linked to
      F9 and 7 newly ascertained families of BP probands. Linkage was also examined
      with the gene encoding the alpha 3 subunit of the gamma-amino butyric acid
      receptor (GABRA3), a candidate gene for BP illness located in this region. The
      genetic data were analyzed with the LOD score method using age-dependent
      penetrance of an autosomal dominant disease gene and narrow and broad clinical
      models. In MAD3 and MAD4 the multipoint LOD score data suggested a localization
      of a BPI gene again near F9. In the 7 new families the overall linkage data
      excluded the Xq27-q28 region. However, if the families were grouped according to
      their proband's phenotype BPI or BPII, a susceptibility gene for BPI disorder at
      the DXS52-F8 cluster could not be excluded.

PMID- 7726218
TI  - Auriculocephalic index: a new anthropometric index for syndrome delineation.
AB  - We describe a new anthropometric index, the "auriculocephalic index." It results
      from the ratio between the length of auricle and the corresponding preauricular
      head height. The index is independent of sex and of age. Normally it ranges
      between 0.25 (-2s) and 0.33 (+2s). In syndrome delineation it may help to
      diagnose more precisely large or small auricles as phenogenetic variants.

PMID- 7726219
TI  - Absent tibiae--polydactyly--triphalangeal thumbs with fibular dimelia: variable
      expression of the Werner (McKusick 188770) syndrome?
AB  - We report on a family in which the autosomal dominant Werner syndrome (WS) (MIM#
      188770) affects ten members in three generations. Besides the absent tibiae the
      propositus had duplication of the fibulae. Possible pathogenetic mechanism is
      discussed.

PMID- 7726220
TI  - Amelia of the arms and femur/fibula deficiency with splenogonadal fusion in a
      child born to a consanguineous couple.
AB  - A male infant was born with symmetrical tetramelic limb deficiency consisting of
      bilateral upper limb amelia with severe symmetrical proximal focal femoral
      deficiency and fibula deficiency associated with left splenogonodal fusion of the
      discontinuous type, micrognathia, and a prominent capillary haemangioma of the
      face. The parents are first cousin Lebanese muslims. This observation suggests
      the possibility of recessive inheritance in some cases of the Amelia, Femur
      Fibula dysostosis syndrome with or without splenogonadal fusion.

PMID- 7726221
TI  - Presence of Y chromosome sequences and their effect on the phenotype of six
      patients with Y chromosome anomalies.
AB  - The extent of Y chromosome material was determined in 6 southern African subjects
      with sex chromosome anomalies. Four of the subjects were phenotypically female,
      and 2 were phenotypically male. Molecular and cytogenetic findings were
      correlated with phenotypic expression. An X;Y translocation was found in both
      male subjects, and in one female subject. The remaining female subjects were
      characterized by an isodicentric Y, an isochromosome Yq, and a micromarker of
      undetermined origin, respectively. The individuals were tested for the presence
      of a number of Y-specific DNA sequences. Molecular findings were generally
      compatible with the cytogenetic findings, and also with the phenotypic sex of the
      patients. All the female subjects had Y material and all but one were negative
      for the sex determining region of the Y (SRY). The somatic Ullrich-Turner-like
      findings present in 3 of the females were attributed to either the presence of a
      45,X cell line and/or a single copy of Xp. The males both showed X;Y
      translocations without any detectable loss of Y DNA. Although molecularly very
      similar, the disparate clinical findings in these 2 subjects could have been
      accounted for by different X inactivation patterns.

PMID- 7726222
TI  - Genital abnormalities in females with Bardet-Biedl syndrome.
AB  - The major manifestations of the Bardet-Biedl syndrome are digital anomalies,
      tapetoretinal degeneration, obesity, renal abnormalities, and hypogenitalism
      (described mainly in males). We report on 2 girls with Bardet-Biedl syndrome who
      also had vaginal atresia. A similar association in females with Bardet-Biedl
      syndrome was suggested in published reports of 11 affected individuals who had
      structural genital abnormalities, (some of which were missed in childhood),
      including persistent urogenital sinus, ectopic urethra, hypoplasia of the uterus,
      ovaries and fallopian tubes, uterus duplex, and septate vagina. The association
      of atresia of the vagina and other malformations of female genital structures in
      individuals with Bardet-Biedl syndrome has often been missed in childhood and
      should be looked for more systematically.

PMID- 7726223
TI  - Prenatal diagnosis of recurrence of short rib-polydactyly syndrome.
AB  - We describe a nonconsanguineous couple whose 3 successive pregnancies, including
      one pair of twins, led to the birth of 4 infants with short rib-polydactyly
      syndrome (SRPS). Flat face, hypoplastic thorax, short limbs and ribs,
      polydactyly, absence of penis, and death after birth were noted in the first
      affected male baby. The affected female twins were detected prenatally by
      ultrasonography and had the same characteristics, but milder than the previous
      one. Serial measurements of the thoracic circumference and the 4 limbs were
      obtained by ultrasound, and showed progressively decreased ratio of thoracic to
      abdominal circumference and shortness of the limbs. The last male baby also had a
      similar but variable expression in prenatal ultrasonography.

PMID- 7726224
TI  - Male pseudohermaphroditism in sibs with the alpha-thalassemia/mental retardation
      (ATR-X) syndrome.
AB  - Genital abnormalities have been noted in several patients with the X-linked form
      of alpha-thalassemia and mental retardation syndrome (ATR-X). The initial
      clinical report of the condition documented a phenotypic female with 46,XY
      karyotype. To this we now add 2 further siblings with abnormalities of the
      external genitalia, manifesting as male pseudohermaphroditism.

PMID- 7726225
TI  - Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental
      retardation syndrome (ATR-X).
AB  - The hallmarks of the X-linked alpha-thalassemia/mental retardation (ATR-X)
      syndrome are severe psychomotor retardation, minor facial anomalies, genital
      abnormalities, and an unusual form of alpha-thalassemia. The demonstration of HbH
      inclusions in red blood cells after incubation with brilliant cresyl blue
      confirms the diagnosis. We describe 15 previously unreported cases and analyse
      the phenotypic and hematologic findings in these subjects and compare them with
      previously published cases. This study demonstrates the consistency of the main
      characteristics of this syndrome and extends the phenotype. Developmental changes
      in phenotype, in particular the coarsening of the facial appearance, are
      illustrated. The hematologic findings are shown to vary widely; in some cases the
      manifestation of alpha-thalassemia may be subtle and missed without repeated
      examination.

PMID- 7726226
TI  - Lumping Juberg-Marsidi syndrome and X-linked alpha-thalassemia/mental retardation
      syndrome?

PMID- 7726227
TI  - X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: a new kindred
      with severe genital anomalies and mild hematologic expression.
AB  - We report a new kindred containing 4 patients with X-linked alpha
      thalassemia/mental retardation syndrome ((ATR-X). Like previously reported ATR-X
      patients, these children are all genetic males with severe developmental delay
      and characteristic facial appearance. The genital anomalies are more severe than
      in most previous cases and have led to a female sex of rearing for 3 of the 4
      patients. The hematologic expression is extremely mild and was not demonstrable
      on routine hematologic studies including hemoglobin electrophoresis, but the
      three living patients all had hemoglobin H inclusions on brilliant cresyl blue
      stained peripheral smears. The combination of skewed X-inactivation and haplotype
      analysis at Xq12-q21.3 confirmed carrier status in the 3 obligate carriers in the
      kindred and led to identification of an additional carrier. Two other women in
      the kindred appear to be noncarriers on the basis of normal X-inactivation and/or
      inheritance of a different Xq12-21.3 haplotype. More widespread use of brilliant
      cresyl blue staining for HbH inclusions in individuals with the facial phenotype
      of ATR-X and/or ambiguous genitalia may lead to the identification of more
      affected patients and improved understanding of the clinical spectrum of ATR-X.

PMID- 7726228
TI  - Familial Mediterranean fever: high gene frequency among the non-Ashkenazic and
      Ashkenazic Jewish populations in Israel.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive recurrent episodic
      inflammatory disorder that occurs with high frequency in certain populations in
      the Mediterranean area. Using extended pedigree data of 90 FMF probands, we
      calculated the FMF gene frequency in various ethnic groups in Israel by analyzing
      the frequency in a total of 2,312 first cousins. The heterozygote frequencies
      were as follows: 1:4.9 (0.2 +/- 0.06) for the Libyan subgroup, 1:6.4 (0.16 +/-
      0.03) for the other North African countries subgroup, 1:13.3 (0.07 +/- 0.04) for
      the Iraqi subgroup, 1:11.4 (0.09 +/- 0.06) for the Ashkenazic subgroup, and
      1:29.4 (0.03 +/- 0.03) for the remaining ethnic groups. The observed number of
      affected parents and offspring of the probands was in agreement with the
      estimated gene frequency. Thus, the FMF gene frequency is very high in all Jewish
      ethnic groups in Israel, especially those originating in North African countries.
      This also explains the parent-to-off-spring transmission of FMF reported in North
      African Jews.

PMID- 7726229
TI  - Ulnar ray defect in an infant with a 6q21;7q31.2 translocation: further evidence
      for the existence of a limb defect gene in 6q21.
AB  - Ectrodactyly is a developmental defect of the distal limbs characterized by
      marked clinical variability and genetic heterogeneity, also reflected in the
      observation of different chromosome abnormalities non randomly associated with
      longitudinal postaxial limb deficiencies. The one most frequently found in
      patients with split hand-split foot (SHSF) involves chromosome band 7q22.
      Recently, structural anomalies of chromosome 6q21 have been reported in 2
      unrelated patients with SHSF, suggesting that this region may also contain genes
      responsible for limb development [Braverman et al., 1993. Am J Hum Genet, suppl
      53: 410; Viljoen and Smart, 1993. Clin Dysmorph 2: 274-277]. We report on a third
      patient who had a de novo, apparently balanced t(6;7)(q21;q31.2) translocation
      and bilateral ulnar aplasia with postaxial oligodactyly. In spite of the
      different phenotypic effects observed in these 3 patients, we consider our case
      as further evidence that genes in 6q21 may play a role in distal limb
      development.

PMID- 7726230
TI  - Lethal congenital non-spherocytic, non-immune hemolytic anemia with genital and
      other anomalies in two brothers.
AB  - Non-consanguineous healthy parents had 2 boys with severe, non-spherocytic,
      nonimmune hemolytic anemia, abnormalities of their external genitalia, flat
      occiput, dimpled earlobes, deep plantar creases, and increased space between
      their first and second toes. The birth of these children was separated by a
      spontaneous abortion at 3 months and delivery of a normal girl. We propose that
      these boys have a heretofore undescribed autosomal or X-linked recessive
      syndrome.

PMID- 7726231
TI  - Clitoromegaly in neurofibromatosis.
AB  - Genitourinary neurofibromas are rare and clitoral involvement in
      neurofibromatosis (NF) has been reported infrequently. However, when it occurs,
      clitoromegaly is often the presenting sign. In many cases, it is congenital. In
      236 families with type 1 neurofibromatosis (NF-1) evaluated through the USF
      Regional Genetics Program between January 1982 and September 1993, four patients
      had clitoral involvement. In three, involvement was limited to the clitoris.
      Biopsy/surgical excision in two of them showed a neurofibroma in one and non
      specific hamartomatous soft tissue overgrowth in the other. In the fourth
      patient, the involvement was asymmetric and extended to the labia majora and mons
      pubis. Endocrine studies and chromosomes in all patients were normal; there was
      no exposure to androgens, progestins, or coumadin. There was no gestational
      history of maternal luteomas. Review of the literature documented 26 patients
      with NF and clitoral involvement. Clitoral involvement in NF-1 appears to be more
      common than previously reported and the differential diagnosis of ambiguous
      genitalia should include clitoromegaly due to NF. Pathogenesis of clitoral
      lesions appears similar to other lesions of NF. Biopsy of such lesions appears to
      be justified only when malignancy is suspected.

PMID- 7726232
TI  - Arthrogryposis multiplex congenita in an Arab kindred: update.
AB  - We have restudied the genetic and clinical characteristics of a large Arab
      kindred previously reported in 1970 by Lebenthal et al. [Pediatrics 46:891-899].
      At total of 40 affected individuals was identified; all, except one, were
      products of 22 different consanguineous matings between the parents. The
      syndrome, which is present at birth, is expressed mainly by flexion contractures
      at the knees and elbows, with muscle hypotrophy/weakness around the involved
      joints. Five of the 6 individuals who were originally reported as having
      congenital and lethal heart defects were limited to one sibship. None of the new
      cases had heart defect or any associated malformation. Neurologic examination and
      electrophysiological studies demonstrated a neuropathic (non-myopathic) type of
      arthrogryposis. This is an autosomal recessive trait with wide variability in
      expression and possibly incomplete penetrance in the females. Because of the high
      consanguinity rate, it allows the use of homozygosity linkage studies to map the
      gene for this disorder.

PMID- 7726233
TI  - Genetic, environmental, and phenotypic links between body mass index and blood
      pressure among women.
AB  - Greater relative weight is associated with higher blood pressure, but the reasons
      are unknown. The inability of current technology to induce sustained weight loss
      among overweight persons precludes experimental tests of whether this association
      is causal. We evaluated the degree to which the covariation between body mass
      index (BMI; kg/m2) and blood pressure (BP) among women is due to pleiotropic
      genetic factors, environmental factors, or phenotypic causation. The sample
      included 75 monozygotic (MZ) and 39 dizygotic (DZ) pairs of adult female twins.
      "BP" was calculated as the unit-weighted mean of systolic and diastolic. Data
      were analyzed through structural equation modeling. A model was specified
      stipulating that additive genetic effects (A) and unique environmental effects
      (E) each contributed to the covariance between BMI and BP, thus allowing for both
      pleiotropic and unique environmental influences on the covariance between BMI and
      BP. Dropping the pleiotropic influences significantly worsened the model (chi 2 =
      4.62, df = 1, P = .032), suggesting significant pleiotropic effects. Dropping the
      environmental influences on the cross-phenotype covariance did not significantly
      worsen the model (chi 2 = 1.42, df = 1, P = .233). This indicates no significant
      effect of the environment on the covariance between BMI and BP. Finally, a model
      of phenotypic causation in which BMI directly influenced BP was fitted. This
      model provided the best single parameter explanation of the BP-BMI covariation.
      These data suggest that, among women, regardless of the source of variation,
      changes in BMI should lead to long-standing changes in BP.

PMID- 7726234
TI  - Duchenne muscular dystrophy and myotonic dystrophy in the same patient.
AB  - We report on the first patient identified with myotonic dystrophy and Duchenne
      muscular dystrophy (DMD). The family of the propositus had a strong history of
      myotonic dystrophy, and there was an intrafamilial pathological expansion of the
      responsible CTG repeat between the mildly affected mother (160 repeats; normal 27
      repeats) and her more severely affected son (650 repeats), and his sister (650
      repeats). The propositus was an isolated case of Duchenne muscular dystrophy with
      marked dystrophin deficiency in muscle biopsy. The patient was still ambulatory
      post age 16. Myotonic dystrophy could interfere to some extent with the
      progression of Duchenne dystrophy. However, other interpretations are possible.
      Twelve percent of dystrophin revertant fibers as observed by immunohistochemistry
      could be sufficient to ameliorate typical DMD clinical severity, or the patient
      may present a somatic mosaic. The pathophysiological interactions of these two
      unlinked disorders are discussed at the clinical and histopathological levels.

PMID- 7726235
TI  - Mulibrey nanism: three additional patients and a review of 39 patients.
AB  - We report on 3 patients with Mulibrey nanism (MN), or Perheentupa syndrome: the
      first 2 sibs from Argentina and a new patient from Spain. All 3 patients had
      growth failure, short stature, abnormal pigmentary retinal changes, and a J
      shaped sella turcica. These findings are considered major criteria of MN. Two had
      pericardial constriction, which is a frequent and life-threatening abnormality in
      this syndrome. MN is a rare autosomal recessive condition. Reviewing the 39
      patients described so far, we have classified the anomalies into the very
      frequent (present in more than 66%), frequent (in at least 25%), and not
      frequent. Identifying the anomalies specific to MN should help its early
      diagnosis and treatment.

PMID- 7726236
TI  - SRY alone can induce normal male sexual differentiation.
AB  - Most individuals with the rare 46,XX male "syndrome" arise due to an unequal
      interchange between Xp and Yp termini during paternal meiosis. The pattern of Y
      sequences in these patients varies considerably, but very few cases have been
      reported showing only SRY. The phenotype in these patients is also variable
      ranging from severe impairment of the external genitalia through hypospadias
      and/or cryptorchidism to occasional normal male phenotype. We report a Mexican
      46,XX male patient without genital ambiguities in whom DNA analysis showed the
      presence of SRY and the absence of ZFY. We conclude that in this case SRY alone
      was enough for complete male sexual differentiation.

PMID- 7726237
TI  - Paracentric inversion X(q21.2q24) associated with mental retardation in males and
      normal ovarian function in females.
AB  - We describe a familial paracentric inversion (X)(q21.2 q24) in a family with 2
      male and 2 female carriers. The males were mentally retarded and the females were
      normal with normal ovarian function. It is suggested that a recessive mental
      retardation (MR) gene was disrupted by one of the inversion breakpoints, although
      an X-linked MR gene which by chance is linked to the inv(X) could not be ruled
      out. In the female carriers of the paracentric inversion a random X-inactivation
      was demonstrated. The normal ovarian function is an exception to the concept of
      "critical region" at Xq13-q26.

PMID- 7726238
TI  - Diabetic embryopathy: possible pathogenesis.
AB  - Despite recent emphasis upon improved metabolic control during early diabetic
      pregnancy, the offspring of insulin-dependent diabetic women continue to have a 2
      to 4-fold increased risk of congenital malformations. We recently evaluated the
      affected offspring of 4 insulin-dependent diabetic women. All had abnormal ears
      in association with vertebral defects. Our analysis of the structural defects of
      these infants and a review of the literature suggest that the pathogenesis of
      some cases of the diabetic embryopathy may involve a primary insult to developing
      somite mesoderm and associated cephalic neural crest cells.

PMID- 7726239
TI  - Myopathy, lactic acidosis, and sideroblastic anemia: a new syndrome.
AB  - We describe 2 sibs (brother and sister) with myopathy, sideroblastic anemia,
      lactic acidosis, mental retardation, microcephaly, high palate, high philtrum,
      distichiasis, and micrognathia. Very low levels of cytochromes a, b, and c were
      detected in the patients' muscle mitochondria. Deposition of iron within the
      mitochondria of bone marrow erythroblasts was observed on electron microscopy.
      Irregular and enlarged mitochondria with paracrystalline inclusions were also
      seen on electron microscopy of the patients' muscle specimen. Examination of DNA
      from the affected sibs showed no deletions in the mitochondrial DNA nor the
      mutations identified in the syndromes of mitochondrial myopathy, encephalopathy,
      lactic acidosis, and strokelike episodes (MELAS) or myoclonus, and epilepsy
      associated with rugged-red fibers (MERRF). Since the parents were first cousins
      and 2 of 6 sibs (male and female) were affected, we suggest that the syndrome
      expressed by our patients represents a previously unknown autosomal recessive
      disorder that includes mitochondrial myopathy, lactic acidosis, and sideroblastic
      anemia.

PMID- 7726240
TI  - De novo interstitial deletion q16.2q21 on chromosome 6.
AB  - A de novo interstitial deletion of 6q16.2q21 was observed in a 23-month-old boy
      with mental and psychomotor delay, obese appearance, minor craniofacial
      anomalies, and brain anomalies. We compare clinical manifestations of this
      patient with those observed in previously reported cases with similar 6q
      interstitial deletions. It is interesting to note the clinical similarities
      between some patients with interstitial deletions of 6q16 or q21 bands and
      patients with Prader-Willi syndrome (PWS) and it may help to keep in mind
      cytogenetic studies of patients with some PWS findings.

PMID- 7726241
TI  - Germline mosaicism at the fragile X locus.
AB  - We have identified a fragile X syndrome pedigree where the disorder is associated
      with a molecular deletion. The deletion was present in the DNA of 2 sons but was
      absent in the mother's somatic cell (lymphocyte) DNA. The results are consistent
      with the deletion arising as a postzygotic event in the mother, who therefore is
      germinally mosaic. This finding has important implications for counseling fragile
      X families with deletion mutations.

PMID- 7726242
TI  - Localization of a gene for X-linked nonspecific mental retardation (MRX24) in
      Xp22.2-p22.3.
AB  - Nonspecific X-linked mental retardation (MRX) includes several distinct genetic
      entities in which mental retardation is not associated with additional
      distinguishing physical changes. We report linkage data in a Spanish family with
      MRX, using polymorphic DNA markers distributed over the X chromosome. Two-point
      linkage analysis demonstrated close linkage between the MRX locus and DXS85 in
      Xp22.3 with a peak lod score of 2.28 at a theta = 0.00. Analysis of multiple
      informative meioses suggested a localization of the MRX locus (MRX24) between
      DXS278 and DXS207. Multipoint linkage analysis resulted in a maximum LOD score of
      2.45 at 3 cM proximal to DXS85, and allowed us to reject a localization of the
      MRX24 gene in all other regions from Xp21-Xqter. These findings localize the
      MRX24 gene in the chromosomal region Xp22.2-p22.3.

PMID- 7726243
TI  - New case of axial mesodermal dysplasia spectrum.

PMID- 7726244
TI  - Future directions for academic obstetrics and gynecology--"... through a glass,
      darkly ...".

PMID- 7726245
TI  - Physician-patient communication using ancestral spirits to achieve holistic
      healing.

PMID- 7726246
TI  - Strategies to respond to polymerase chain reaction deoxyribonucleic acid
      amplification failure in a preimplantation genetic diagnosis program.
AB  - OBJECTIVES: Our purpose was to identify and evaluate practical methods within a
      preimplantation genetic diagnosis program that will increase the percentage of
      embryos for which a genetic diagnosis can be obtained, including clinical
      responses after failure of deoxyribonucleic acid amplification has occurred.
      STUDY DESIGN: Known human lymphoblast cell lines and human embryo blastomeres
      were evaluated in a single-cell, nested primer polymerase chain reaction system
      with primer sequences for the specific locus surrounding the four base pair
      insertion mutation on exon 11 of beta-hexosaminidase A-Tay-Sachs disease, the
      delta F508 mutation of cystic fibrosis, and the sex-determining region on the Y
      chromosome. Reamplification polymerase chain reaction with standard polymerase
      chain reaction and primer extension preamplification was performed in
      deoxyribonucleic acid preparations after previous polymerase chain reaction
      amplification attempts had resulted in failure of amplification. RESULTS: The
      amplification efficiency of Tay-Sachs disease, 51% (97/187), was significantly
      lower than that for cystic fibrosis, 85% (87/107), and for the sex-determining
      region on the Y chromosome, 85% (77/90). Tay-Sachs disease polymerase chain
      reaction amplification occurred in 51% of one-cell lymphoblasts, 89% of two-cell
      lymphoblasts, and 94% of samples when more than two cells were processed
      together. When previous amplification failure had occurred, standard Tay-Sachs
      disease polymerase chain reaction resulted in an amplification efficiency of 16%
      (three of 19), whereas primer extension preamplification polymerase chain
      reaction for Tay-Sachs disease resulted in amplification of 52% (31/59)
      lymphoblasts and 54% (13/24) of polyspermic human blastomeres. Four of six human
      blastomeres in which amplification failure occurred in a Tay-Sachs disease
      preimplantation genetic diagnosis cycle amplified by primer extension
      preamplification polymerase chain reaction, which increased the diagnostic
      information obtained from four to six of the seven embryos on which biopsy was
      performed. CONCLUSIONS: We suggest that practical approaches for consideration
      within a clinical preimplantation genetic diagnosis program to limit the net
      effect of amplification failure (i.e., reduced embryo transfer number) include
      increasing the deoxyribonucleic acid content in the polymerase chain reaction
      tube by using more than one blastomere and by using primer extension
      preamplification when the initial attempt at amplification fails.

PMID- 7726247
TI  - Cervical competence as a continuum: a study of ultrasonographic cervical length
      and obstetric performance.
AB  - OBJECTIVE: Our purpose was to investigate the hypothesis that cervical competence
      is a continuum that is related to cervical length and is reflected by pregnancy
      history. STUDY DESIGN: A cross-sectional study was performed of cervical length
      measured by transvaginal ultrasonography in women with prior preterm delivery at
      < or = 26 weeks, 27 to 32 weeks, and 33 to 35 weeks compared with women with
      cervical incompetence and normal controls delivered at term. RESULTS:
      Transvaginal cervical length was measured during pregnancy in 32 subjects with
      cervical incompetence, 98 with previous preterm birth < or = 26 weeks, 98 with
      previous preterm birth at 27 to 32 weeks, 127 with previous preterm birth at 33
      to 35 weeks, and 106 normal controls. The relationship between obstetric history
      and cervical length was evaluated by analysis of variance. The gestational age at
      the first preterm delivery was significantly correlated with cervical length in
      the current pregnancy at each gestational interval between 20 and 30 weeks in a
      continuous manner. CONCLUSION: Cervical competence is a continuous rather than
      categoric variable and is indicated indirectly by measurement of the length of
      the cervix.

PMID- 7726248
TI  - Postpartum plasma exchange for atypical preeclampsia-eclampsia as HELLP
      (hemolysis, elevated liver enzymes, and low platelets) syndrome.
AB  - OBJECTIVE: Our purpose was to investigate the postpartum use of plasma exchange
      in patients considered to have atypical preeclampsia-eclampsia manifested as
      persistent HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome
      with or without evidence of other organ injury. STUDY DESIGN: During a 10-year
      period, 18 patients with HELLP syndrome were treated post partum with single or
      multiple plasma exchange with fresh-frozen plasma. Each patient was entered into
      the clinical trial either because of persistent evidence of atypical preeclampsia
      eclampsia as HELLP syndrome > 72 hours after delivery (group 1) or with evidence
      of worsening HELLP syndrome at any time post partum in association with single-
      or multiple-organ injury (group 2). All procedures were performed with the IBM
      2997 Cell Separator (IBM, Cobe Laboratories, Inc., Lakewood, Colo.) system.
      Maternal and perinatal outcomes were the main outcomes studied. RESULTS: In the
      absence of other disease conditions, the 9 patients in group 1 with persistent
      postpartum HELLP syndrome complicated only by severe clinical expressions of
      preeclampsia-eclampsia responded rapidly to one or two plasma exchange procedures
      with few complications and no maternal deaths. In contrast, in the 9 patients of
      group 2 with HELLP syndrome presentations complicated by other organ disease, the
      response to plasma exchange was variable and there were two deaths in this group.
      CONCLUSION: The current series of patients details the successful postpartum
      application of plasma exchange therapy for unremitting HELLP syndrome but reveals
      that a uniformly positive response to this therapy will not always be observed
      when there is additional single or multiple organ injury.

PMID- 7726249
TI  - Use of levonorgestrel implants versus oral contraceptives in adolescence: a case
      control study.
AB  - OBJECTIVE: We compared continuation rates, effectiveness, satisfaction with
      method, side effects, and condom practices among adolescents using levonorgestrel
      implants (Norplant, Wyeth-Ayerst Laboratories, Philadelphia) as compared with
      oral contraceptives. STUDY DESIGN: We conducted a case-control study comparing 94
      adolescents < or = 18 years old who received Norplant between March 1, 1992, and
      Nov. 1, 1993 (cases), with 94 age-matched controls who selected oral
      contraceptives during this same time period. By use of a structured
      questionnaire, information was obtained on pregnancy status, duration of use,
      patient satisfaction, side effects, and condom practices 6 months after
      initiation. Objective measures included weight on Norplant and oral contraceptive
      users and hematocrit on implant patients. RESULTS: Forty (43%) oral contraceptive
      patients compared with no Norplant patients discontinued their selected method
      before the 6-month interview (p = 0.00). Six patients prescribed oral
      contraceptives became pregnant. Ninety-three percent of Norplant users expressed
      overall satisfaction despite experiencing menstrual irregularity and cramping,
      amenorrhea, nervousness, abnormal hair growth or loss, rashes, and an increase in
      appetite more often than oral contraceptive users. Although Norplant patients
      also reported an increase in the duration of menstrual flow and number of days of
      spotting more often than oral contraceptive users, evaluation of hematocrits in
      these patients demonstrated a significant increase over the 6-month period (p =
      0.00). Assessment of condom practices since initiation demonstrated that Norplant
      patients used condoms less often than oral contraceptive users (p = 0.00).
      CONCLUSION: Use of levonorgestrel implants may cause more side effects than oral
      contraceptives in the early months after initiation but provide superior
      protection against unintended pregnancy. We concluded that Norplant is a
      reasonable alternative for adolescents, especially when compliance is an issue.

PMID- 7726250
TI  - An evaluation of human papillomavirus testing for intermediate- and high-risk
      types as triage before colposcopy.
AB  - OBJECTIVE: Our purpose was to evaluate the role of testing for intermediate- and
      high-risk human papillomavirus by use of a hybrid capture technique for
      predicting which patients with abnormal Papanicolaou smears are most likely to
      have squamous intraepithelial lesions or cancer. STUDY DESIGN: Cervical cytologic
      studies, hybrid capture tests, and colposcopically directed biopsies were
      performed on 311 women referred to the colposcopy clinics with abnormal cytologic
      study results. RESULTS: There was a highly significant correlation (p < 0.0001)
      between a positive human papillomavirus test and the finding of squamous
      intraepithelial lesions or invasive cancer. The sensitivity of human
      papillomavirus testing to detect high-grade squamous intraepithelial lesions was
      74% when it was used alone and increased to 91% when coupled with abnormal
      cytologic study results of low- or high-grade squamous intraepithelial lesions or
      cancer. In 44 women with atypical squamous cells of undetermined significance on
      cytologic study, human papillomavirus testing identified six of 10 who had high
      grade squamous intraepithelial lesions. For the 96 patients with low-grade
      squamous intraepithelial lesions, human papillomavirus testing was successful in
      identifying 29 of the 37 with high-grade squamous intraepithelial lesions
      (sensitivity 0.76). CONCLUSION: Testing for intermediate- and high-risk human
      papillomavirus types by hybrid capture improves the detection of high-grade
      squamous intraepithelial lesions in women with atypical squamous cells of
      undetermined significance and low-grade squamous intraepithelial lesions over
      cytologic study used alone.

PMID- 7726251
TI  - Amniotic fluid embolism: analysis of the national registry.
AB  - OBJECTIVE: We analyzed the clinical course and investigated possible
      pathophysiologic mechanisms of amniotic fluid embolism. STUDY DESIGN: We carried
      out a retrospective review of medical records. Forty-six charts were analyzed for
      121 separate clinical variables. RESULTS: Amniotic fluid embolism occurred during
      labor in 70% of the women, after vaginal delivery in 11%, and during cesarean
      section after delivery of the infant in 19%. No correlation was seen with
      prolonged labor or oxytocin use. A significant relation was seen between amniotic
      fluid embolism and male fetal sex. Forty-one percent of patients gave a history
      of allergy or atopy. Maternal mortality was 61%, with neurologically intact
      survival seen in 15% of women. Of fetuses in utero at the time of the event, only
      39% survived. Clinical and hemodynamic manifestations were similar to those
      manifest in anaphylaxis and septic shock. CONCLUSIONS: Intact maternal or fetal
      survival with amniotic fluid embolism is rare. The striking similarities between
      clinical and hemodynamic findings in amniotic fluid embolism and both anaphylaxis
      and septic shock suggest a common pathophysiologic mechanism for all these
      conditions. Thus the term amniotic fluid embolism appears to be a misnomer.

PMID- 7726252
TI  - A comparison of cardiopulmonary adaptations to exercise in pregnancy at sea level
      and altitude.
AB  - OBJECTIVE: The purpose of this study was to compare maternal cardiopulmonary and
      fetal responses of lowlander pregnant women in the third trimester to exercise at
      sea level and at an altitude of 6000 feet. STUDY DESIGN: Seven women at 33.86 +/-
      1 weeks' gestation performed a symptom-limited maximal exercise test and a
      submaximal cardiac output exercise test at sea level at an altitude of 6000 feet.
      Cardiopulmonary and metabolic variables were measured and compared at sea level
      and altitude. RESULTS: Maximal oxygen consumption and work levels were limited by
      short-term altitude exposure. Ventilatory variables were not significantly
      influenced by altitude exposure. During submaximal exercise no alteration in
      exercise efficiency or response was seen for most of the variables when altitude
      and sea level data were compared. Both cardiac output and stroke volume were
      elevated at altitude at rest but not during exercise, suggesting a lower reserve
      for both variables at altitude. Level of plasma glucose, lactate, norepinephrine,
      and epinephrine were not significantly influenced by altitude exposure. Fetal
      heart rate responses did not differ between the sea level and altitude
      conditions. CONDITIONS: Lowlander pregnant women in the third trimester have some
      limitations to maximal aerobic capacity but not submaximal exercise on short-term
      altitude exposure. No ominous fetal responses have been observed during this
      study. The results suggest that pregnant women may engage in at least brief
      moderate exercise bouts at moderate altitude without adverse consequences.

PMID- 7726253
TI  - The obstetrician and gynecologist: primary care physician or specialist?

PMID- 7726254
TI  - The obstetrician-gynecologist: specialist and primary care physician.

PMID- 7726255
TI  - The obstetrician-gynecologist--generalist, specialist, subspecialist?

PMID- 7726256
TI  - Assessment of numeric abnormalities of X, Y, 18, and 16 chromosomes in
      preimplantation human embryos before transfer.
AB  - OBJECTIVE: Our purpose was to determine the feasibility of ascertaining
      aneuploidy for chromosomes X, Y, 18, and 16 by use of multiple-probe fluorescence
      in situ hybridization in blastomeres from preimplantation human embryos. STUDY
      DESIGN: A short fluorescence in situ hybridization procedure involving the
      simultaneous use of four deoxyribonucleic acid probes detected with red, green,
      blue, or a mixture of red and green fluorochromes was developed to determine
      numeric abnormalities of chromosomes X, Y, 18, and 16. Embryos underwent biopsy,
      and all or most cells were analyzed to distinguish true aneuploidy from mosaicism
      and to assess technique variations within the same embryo (n = 64). RESULTS: The
      analysis of all the blastomeres of an embryo was achieved in 91% of the embryos.
      Successful analyses including biopsy, fixation, and fluorescence in situ
      hybridization were achieved in 87.8% of the blastomeres. Of the four chromosomes
      tested, numeric aberrations were found in 23% and 42% of normally and abnormally
      developing embryos, respectively, including aneuploidy, polyploidy, haploidy, and
      mosaicism. When diploid embryos containing one or several tetraploid cells are
      counted as chromosomally abnormal, then 49% and 61% of normally and abnormally
      developing embryos, respectively, were chromosomally abnormal. Aneuploid embryos
      consisted of two monosomies for chromosome 16, one for chromosome 18, and a
      trisomy for chromosome 16. There was a tendency for aneuploidy to increase with
      maternal age. CONCLUSIONS: Fluorescence in situ hybridization is a more efficient
      method than cytogenetic analysis to study specific aneuploidies at
      preimplantation stages of development in human embryos. In addition, the
      preimplantation genetic diagnosis of two blastomeres per eight-cell embryo may be
      sufficient to ensure successful analysis of polyploidy, haploidy, and specific
      aneuploidies without endangering the survival of the embryo. The technique can be
      easily modified to consider other chromosomes, including 13 and 21. Because most
      chromosomally abnormal embryos do not develop to term, the use of this technique
      may increase the delivery rate per embryo by allowing only transfer of embryos
      normal for the tested chromosomes. This technique would be most useful for older
      women undergoing in vitro fertilization, because aneuploidy appears to increase
      with advancing maternal age.

PMID- 7726257
TI  - Fetoscopic laser ablation of placental vessels in severe previable twin-twin
      transfusion syndrome.
AB  - OBJECTIVE: We undertook a pilot study to determine the feasibility and efficacy
      of fetoscopic laser occlusion of chorioangiopagous vessels in severe previable
      twin-twin transfusion syndrome. STUDY DESIGN: A total of 35 patients were
      referred to the investigators with ultrasonographic findings consistent with twin
      twin transfusion syndrome, posterior placental implantation, gestational age < 25
      weeks, and clinical hydramnios. Placental vessel occlusion was performed with a
      rigid 2.9 x 3.85 mm dual-channel fetoscope and neodymium:yttrium-aluminum-garnet
      laser light. RESULTS: Of the original 35 patients, 5 were eliminated
      preoperatively and 4 intraoperatively for various factors. The 26 treated
      patients had a mean gestational age of 20.8 weeks (range 18 to 24) and a mean
      fundal height of 36.1 cm (range 29 to 44). One patient has surviving triplets, 8
      have surviving twins, 9 have a single survivor (2 neonatal and 7 fetal deaths
      occurred in this group), and 8 have no survivors (all had pregnancy loss within 3
      weeks of treatment). The cases with survivors were delivered for obstetric
      indications at a mean of 32.2 weeks (range 26 to 37), having gained a mean of
      11.7 weeks (range 6 to 17) in utero. Fifty-three percent (28/53) of the fetuses
      survived with 96% (27/28) developing normally at a mean age of 35.8 months (range
      1 to 68). Thirty-three of 35 placentas were monochorionic with chorioangiopagous
      vessels on gross and microscopic evaluation. CONCLUSIONS: Fetoscopic laser
      occlusion of chorioangiopagous vessels is technically feasible and improves the
      course and outcome of severe twin-twin transfusion syndrome in previable fetuses.

PMID- 7726258
TI  - Markers of acute and chronic asphyxia in infants with meconium-stained amniotic
      fluid.
AB  - OBJECTIVE: Cord blood pH, lactate, hypoxanthine, and erythropoietin levels have
      all been used as markers of either acute or chronic asphyxia. We sought to
      determine whether these index values were significantly different in infants with
      or without meconium-stained amniotic fluid. STUDY DESIGN: Fifty-six pregnant
      women in spontaneous labor at term were divided into two groups on the basis of
      the presence or absence of meconium-stained amniotic fluid. All meconium-stained
      fluid was centrifuged, and the volume percentage of particulate matter (i.e.,
      meconium) was recorded. Umbilical artery blood and mixed arterial and venous cord
      blood were obtained at each delivery. Lactate, hypoxanthine, and erythropoietin
      levels were measured. Statistical analysis included Student t test and rank sum
      statistics where appropriate. Normal and Spearman correlation coefficients were
      also used. RESULTS: There were no significant differences in mean umbilical
      artery pH (7.26 +/- 0.06 vs 7.25 +/- 0.10), lactate levels (32.8 +/- 10 mg/dl vs
      30.4 +/- 14.2 mg/dl), and hypoxanthine levels (13.4 +/- 6.7 mumol/L vs 14.0 +/-
      6.0 mumol/L) in newborns with meconium (n = 28) compared with controls (n = 28).
      Erythropoietin levels were significantly greater in newborns with meconium
      (median 39.5 mIU/ml vs 26.8 mIU/ml, p = 0.039). There was no correlation between
      the amount of particulate matter and any marker of asphyxia. CONCLUSIONS: There
      was no correlation between markers of acute asphyxia (i.e., umbilical artery
      blood pH, lactate, or hypoxanthine) and meconium. However, erythropoietin levels
      were significantly elevated in newborns with meconium-stained amniotic fluid.
      This latter marker may better correlate with chronic asphyxia.

PMID- 7726259
TI  - Fetal membranes inhibit prostaglandin but not oxytocin-induced uterine
      contractions.
AB  - OBJECTIVE: Paracrine signaling in fetal membranes and uterus is hypothesized to
      play a role in the initiation of labor in women. Numerous fetal membrane signals
      that stimulate uterine contractions have been described. Recently, by means of
      the dual-chamber, fetal membrane, uterine muscle model we showed that fetal
      membranes inhibit spontaneous uterine contractions. This study was designed to
      test whether human fetal membranes can also inhibit agonist-induced uterine
      contractions. STUDY DESIGN: A rat uterine muscle strip was mounted into the
      maternal side of a Plexiglas acrylic plastic chamber. Uterine contractions were
      recorded for 3 hours after the addition of either 50 nmol/L prostaglandin E2 or
      0.1 nmol/L oxytocin to the maternal side of the chamber. During the first and
      third hours no fetal membranes were present (basal condition). At the beginning
      of the second hour fetal membranes were inserted into the chamber so that they
      divided the chamber into maternal and fetal compartments. The membranes were
      removed before the beginning of the third hour. The integrated force of uterine
      contractions during the second hour, when the muscle was exposed to fetal
      membranes, was compared with the basal condition (first and third hours) by
      repeated-measure analysis of variance. RESULTS: Fetal membranes reversibly
      inhibited prostaglandin E2-induced uterine contractions by 22%. Fetal membranes
      did not inhibit oxytocin-induced uterine contractions. CONCLUSION: Fetal
      membranes inhibit agonist-induced uterine contractions. The fetal membrane
      inhibitory system is agonist selective.

PMID- 7726261
TI  - Combining humerus and femur length for improved ultrasonographic identification
      of pregnancies at increased risk for trisomy 21.
AB  - OBJECTIVE: Our purpose was to evaluate the value of the combination of femur and
      humerus length measurements in ultrasonographic screening for trisomy 21. STUDY
      DESIGN: Direct necropsy measurements were analyzed on 703 midgestational fetuses
      (641 normal, 62 with trisomy 21). The (leg+arm length)/foot length ratio was
      found to be significantly shortened for fetuses with trisomy 21. On the basis of
      necropsy data 576 midgestational pregnancies were evaluated ultrasonographically
      for (femur+humerus length)/foot length ratio to identify fetuses at increased
      risk for trisomy 21. RESULTS: An ultrasonographic (femur+humerus length)/foot
      length ratio < or = 1.75 gave a 15.3 odds ratio risk for trisomy 21 in our high
      risk population and correctly identified 53% of fetuses with trisomy 21, with a
      false-positive rate of 7%. In addition, the use of this ratio eliminates the need
      for gestational age-corrected nomograms and complicated calculations in
      ultrasonographic screening. CONCLUSION: The (femur+humerus length)/foot length
      ratio may be an additional effective ultrasonographic marker for identification
      of fetuses at increased risk for trisomy 21.

PMID- 7726260
TI  - Fetal behavioral state patterns during and after prolonged exposure to cocaine in
      sheep.
AB  - OBJECTIVE: Studies on the effects of cocaine in fetal animals have been limited
      to acute exposures to the drug. We hypothesized that a prolonged infusion of
      cocaine to the fetal sheep would initially interrupt normal behavioral state
      cycling but the effects would be short lived as the fetus gained tolerance to the
      drug. STUDY DESIGN: The study was performed in a university laboratory on six
      time-dated pregnant ewes at 125 days' gestation. Fetal sheep, surgically
      instrumented 3 days before study, were given cocaine hydrochloride 0.6 mg/min for
      6 hours. Fetal behavioral state before, during, and after the infusion was
      compared by repeated-measures analysis of variance. RESULTS: Infusion of cocaine
      caused a drop in the percentage time that the fetuses spent in both rapid-eye
      movement (p < 0.03) and non-rapid-eye movement (p < 0.001) sleep, which was
      sustained throughout the 6-hour infusion. This was related to a decrease in the
      number of rapid-eye-movement and non-rapid-eye-movement episodes as opposed to a
      decrease in the lengths of these behavioral states. With cessation of cocaine
      infusion, the fetal sheep showed an increase in rapid-eye-movement sleep, with a
      higher percentage than during control periods (p < 0.02). CONCLUSIONS: Cocaine
      disrupts fetal rapid-eye-movement sleep without evidence for tolerance to the
      drug over a 6-hour period. "Catch-up" rapid-eye-movement sleep occurs with
      cessation of cocaine infusion. Neurobehavioral abnormalities associated with in
      utero cocaine exposure may be caused by chronic disruption of rapid-eye-movement
      sleep.

PMID- 7726262
TI  - Carrier diagnosis of the fragile X syndrome--a challenge in antenatal clinics.
AB  - OBJECTIVE: The fragile X syndrome, a common cause of mental retardation, is
      poorly recognized even in families at risk. The aims of our study were to
      evaluate the possibility of finding previously unidentified carriers of the
      genetic defect in fragile X families, to use this information in antenatal
      diagnosis, and to study the attitudes of these families to genetic screening.
      STUDY DESIGN: We identified 59 fragile X families living in a population of
      900,000 inhabitants. A deoxyribonucleic acid test on the FMR1 gene was offered to
      1071 persons in these families who had a risk of at least 12.5% of having the
      fragile X premutation or full mutation. RESULTS: A total of 48.1% of the persons
      who were offered the test accepted it. A diagnosis was made in 20 male and 66
      female subjects with the full mutation and in 30 male and 133 female subjects
      with a premutation. All 21 pregnant carriers of this mutation accepted chorionic
      villus biopsy. CONCLUSION: Pregnant relatives should be informed of the
      availability of screening for fragile X carrier status in families with a member
      having clinical fragile X syndrome. Antenatal clinics offer a good gateway for
      approaching families with this inherited developmental defect.

PMID- 7726263
TI  - Amplifying effect of endothelin-1 on serotonin-induced vasoconstriction of human
      umbilical artery.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of endothelin-1 in
      serotonin-induced vasoconstriction in human umbilical artery. STUDY DESIGN:
      Umbilical arteries collected from 41 normal subjects at term were cut helically
      and suspended in an organ bath for recording isometric mechanical activity. In
      study 1 we measured the concentration-contraction response to serotonin or
      endothelin-1 according to a cumulative concentration schedule. In study 2 vessels
      were preincubated with a subthreshold concentration of endothelin-1 (100, 250, or
      500 pg/ml), and then serotonin was added cumulatively. In study 3 vessels were
      preincubated with H-7 (3 x 10(-6) mol/L), an inhibitor of protein kinase C, or
      with 12-tetradecanoylphorbol-13 acetate (10(-9) to 10(-7) mol/L), an activator of
      protein kinase C; then serotonin was added cumulatively. In study 4 vessels were
      suspended in a calcium-free solution containing 2 mmol/L ethylene glycol-bis(beta
      aminoethyl ether) N,N,N',N'-tetraacetic acid and 60 mmol/L potassium chloride,
      and then a cumulative concentration-response curve to calcium chloride (10(-7) to
      10(-3) mol/L) was constructed for vessels pretreated with endothelin-1, 500 pg/ml
      or 5 ng/ml. RESULTS: The threshold concentrations of serotonin and endothelin-1
      were 5 and 1 ng/ml, respectively. A subthreshold concentration of endothelin-1
      (250 or 500 pg/ml) potentiated significantly the concentration response to
      serotonin (p < 0.084, p < 0.009, by analysis of variance). Pretreatment with H-7
      significantly suppressed the amplifying effect of endothelin-1 on serotonin
      induced contraction. Treatment with 12-tetradecanoylphorbol-13 acetate (10(-7) or
      10(-8) mol/L) significantly potentiated the contractile response to serotonin (p
      < 0.0003, p < 0.015). The sensitivity of the arterial segments to calcium
      chloride in the presence of a subthreshold concentration of endothelin-1 did not
      differ from that in the control group. CONCLUSION: Endothelin-1 at a subthreshold
      concentration amplified the smooth muscle contraction induced by serotonin. The
      mechanism of action may be mediated by activation of intracellular protein kinase
      C.

PMID- 7726265
TI  - Chronic hyperinsulinemia and the adrenal androgen response to acute corticotropin
      (1-24) stimulation in hyperandrogenic women.
AB  - OBJECTIVE: Many women with androgen excess demonstrate elevated circulating
      insulin levels independent of obesity. In addition, in these women some
      investigators have demonstrated a negative correlation between the circulating
      levels of the adrenal androgens, dehydroepiandrosterone or dehydroepiandrosterone
      sulfate and insulin. The mechanism by which insulin decreases adrenal androgens
      is unclear. The objective of this study was to determine whether chronic
      hyperinsulinemia in hyperandrogenic women results in an alteration in the
      adrenocortical response to corticotropin, resulting in decreased androgen
      secretion. STUDY DESIGN: We studied seven hyperandrogenic women with severe
      chronic hyperinsulinemia and eight hyperandrogenic normoinsulinemic patients.
      Nine healthy women served as controls for the basal hormonal levels and the
      response to a 3-hour, 100 gm oral glucose tolerance test. In all subjects insulin
      and glucose were measured hourly during the oral glucose tolerance test and the
      baseline sample was assayed for total testosterone, dehydroepiandrosterone
      sulfate, dehydroepiandrosterone, androstenedione, sex hormone-binding globulin,
      and free testosterone. In hyperandrogenic women cortisol, dehydroepiandrosterone,
      and androstenedione were also measured, before and 60 minutes, after acute
      intravenous administration of 0.25 mg corticotropin (1-24). RESULTS: There was no
      difference in the response of cortisol, dehydroepiandrosterone, or
      androstenedione to corticotropin-(1-24) stimulation between normoinsulinemic and
      hyperinsulinemic hyperandrogenic patients. As defined, the hyperinsulinemic
      patients had higher basal and peak insulin levels and areas under the insulin
      response curve compared with the normoinsulinemic patients or controls. Total
      testosterone and dehydroepiandrosterone did not differ among study groups. As
      expected, hyperandrogenic patients demonstrated lower sex hormone-binding
      globulin activity and higher free testosterone, androstenedione, and
      dehydroepiandrosterone sulfate basal levels compared with controls. CONCLUSIONS:
      The results of this study do not support the hypothesis that chronic
      hyperinsulinemia in hyperandrogenic patients significantly inhibits the
      andrenocortical secretion of dehydroepiandrosterone or androstenedione in
      response to corticotropin stimulation or the basal circulating adrenal androgen
      levels. Additional studies, including a greater number of patients, may be needed
      to fully establish these conclusions.

PMID- 7726264
TI  - The effect of cervical loop electrosurgical excision on subsequent pregnancy
      outcome: North American experience.
AB  - OBJECTIVE: Our purpose was to determine pregnancy outcome and parturition in
      women who were treated by loop electrosurgical excision for squamous
      intraepithelial lesions. STUDY DESIGN: A series of 574 consecutive women of
      reproductive age (15 to 44 years old) were treated by loop electroexcision for
      low- and high-grade squamous intraepithelial lesions. The incidence of
      pregnancies was determined in these women within a 3-year period after therapy by
      comparing the "observed" number of pregnancies with the "expected" number of
      pregnancies in the study population, assuming that fertility rates in these women
      were the same as in the untreated general female population. Pregnancy outcome
      was correlated in the 53 women who were delivered of an infant with the
      posttreatment appearance of the cervix and birth weight with maternal smoking.
      RESULTS: The incidence of pregnancy in the study population was 8.5 per 100 woman
      years compared with 7.4 per 100 woman years in the untreated central population.
      Fifty-three women had 54 pregnancies, of which 46 (84%) were live births either
      at term (40) or between 37 and 39 weeks of gestation (6), and three patients are
      at present at 24, 34, and 36 weeks of gestation. There were two stillbirths and
      three first-trimester spontaneous abortions. Premature delivery was not observed.
      External os stenosis (one case), shortening of the cervix (one case), and repeat
      electroexcision (four cases) had no adverse effect on pregnancy and parturition.
      Smoking > or = 10 cigarettes per day before and during pregnancy, rather than
      loop electrosurgical excision per se, was associated with lower-birth-weight
      babies than those of nonsmokers (p < 0.01). CONCLUSION: Loop electrosurgical
      excision to a maximum depth of 1.5 cm and a mean frontal diameter of 1.8 cm does
      not appear to have adverse effects on subsequent pregnancy outcome and
      parturition.

PMID- 7726267
TI  - Single oral dose fluconazole compared with conventional clotrimazole topical
      therapy of Candida vaginitis. Fluconazole Vaginitis Study Group.
AB  - OBJECTIVES: Candida vaginitis is currently treated with a wide range of
      intravaginal preparations usually prescribed over several days. Fluconazole with
      its marked activity against Candida species and favorable pharmacokinetics
      offered a safe, effective, and convenient alternative to topical therapy in a
      single-dose regimen. STUDY DESIGN: We conducted a multicenter, randomized,
      prospective, single-blinded study of 429 patients with acute Candida vaginitis,
      comparing the efficacy and safety of a single oral 150 mg dose of fluconazole
      with 7-day clotrimazole 100 mg vaginal treatment. Posttherapy evaluations and
      mycologic eradication rates were conducted. RESULTS: No statistically significant
      differences were seen between fluconazole and clotrimazole in the clinical,
      mycologic, or therapeutic responses. At the 14-day evaluation clinical cure or
      improvement was seen in 94% of fluconazole-treated patients and 97% of
      clotrimazole-treated patients. Mycologic and therapeutic cures were seen in 77%
      and 76% of the fluconazole and 72% of the clotrimazole groups, respectively. At
      the 35-day evaluation 75% of both groups remained clinically cured, and 56% of
      the fluconazole and 52% of the clotrimazole group were considered therapeutic
      cures. In both treatment groups patients with a history of recurrent vaginitis
      (33/84) compared with those without a history of recurrent vaginitis (177/266)
      were significantly less likely to respond clinically and mycologically (p <
      0.001). Twenty-seven percent of the fluconazole-treated patients and 17% of the
      clotrimazole-treated patients reported mild side effects only. CONCLUSION:
      Fluconazole administered as a single 150 mg oral dose proved to be as safe and
      effective as 7 days of intravaginal clotrimazole therapy for Candida vaginitis.
      Therapy of vaginitis should be individualized, taking into consideration severity
      of disease, history of recurrent vaginitis, and patient preference.

PMID- 7726266
TI  - Loop electrosurgical excision with a laparoscopic electrode and carbon dioxide
      laser vaporization: comparison of thermal injury characteristics in the rat
      uterine horn.
AB  - OBJECTIVE: Our purpose was to compare the thermal intraperitoneal injury in
      lesions resulting from a monopolar electrosurgical loop electrode designed for
      laparoscopic surgery with similar lesions fashioned by carbon dioxide laser
      vaporization. STUDY DESIGN: A randomized, observer-blinded comparison was made of
      histopathologically measured thermal injury in rat uterine horns. The primary
      outcome measure was the depth of necrotic debris and coagulative necrosis in the
      lesions created by the two methods. RESULTS: The depth of coagulative necrosis
      was similar in the laser vaporization (0.118 +/- 0.028 mm) and the loop excision
      groups (0.165 +/- 0.167 mm). However, the average amount of necrotic debris was
      greater in the lasered lesions (0.053 +/- 0.019 mm) compared with those made with
      the loop electrode (0.013 +/- 0.011 mm). CONCLUSIONS: The depth of coagulative
      necrosis in rat uterine lesions fashioned with a loop electrode is similar to
      that of lesions created by carbon dioxide vaporization at power densities
      comparable with those usually achieved at laparoscopic surgery. There is a
      greater amount of necrotic debris in the lasered lesions. This suggests that
      electrosurgical loops designed for laparoscopic surgery may have promise for the
      cost-effective excision of intraperitoneal tissue.

PMID- 7726268
TI  - Antichlamydial activity of vaginal secretion.
AB  - OBJECTIVE: The purpose of this study was to investigate the possible
      antichlamydial activity of vaginal secretion and to partially characterize the
      inhibitory principle. STUDY DESIGN: Vaginal secretions obtained from 156 women
      attending a family planning or gynecologic outpatient clinic for contraceptive
      advice were studied for the influence on the inclusion formation of Chlamydia
      trachomatis in cycloheximide-treated McCoy cell cultures. RESULTS: Vaginal
      secretions from 156 women inhibited the inclusion formation of Chlamydia
      trachomatis. The inhibition was concentration dependent and the inhibitory
      principle had a molecular weight of < 10,000 d. It was heat labile. It was not
      related to antichlamydial antibodies in vaginal secretions. Only three (2%) of
      the women had a positive culture for Chlamydia trachomatis. Three had
      immunoglobulin A and three had immunoglobulin G antichlamydial antibodies in
      vaginal secretions. Secretions of those with a vaginal pH of 3.5 to 4.5 decreased
      the chlamydial inclusion count by 75% compared with controls. The corresponding
      percentage for those with a pH of 5.0 to 6.0 was 48% and for those with pH > 6
      was 33%. Vaginal secretions of oral contraceptive users and nonusers did not
      differ in the capacity to decrease the chlamydial inclusion count, p > 0.01.
      CONCLUSIONS: When vaginal secretions were added to McCoy cell cultures infected
      by Chlamydia trachomatis, the chlamydia inclusion number decreased. There was a
      correlation between pH of the vaginal secretion and the inhibitory principle.
      Oral contraceptive use had no influence on the inhibition.

PMID- 7726269
TI  - Hormonal status affects the reactivity of the cerebral vasculature.
AB  - OBJECTIVE: We compared the blood velocity and vascular resistance in the central
      retinal and ophthalmic arteries in healthy nonpregnant, pregnant, and
      postmenopausal women (before and after estrogen replacement therapy). STUDY
      DESIGN: Color flow Doppler ultrasonography was used to determine systolic,
      diastolic, and mean velocity, as well as the resistance index in the central
      retinal and ophthalmic arteries in 10 nonpregnant women, 10 third-trimester
      pregnant women, and 10 hypoestrogenic postmenopausal women. The postmenopausal
      patients were again studied 2 months after starting daily oral therapy with 2 mg
      of micronized 17 beta-estradiol. RESULTS: Pregnant women had a significantly (p <
      0.05) higher diastolic blood velocity (4.2 +/- 0.8 cm/sec) and a lower resistance
      index (0.56 +/- 0.05) in the central retinal artery, when compared with
      nonpregnant women (diastolic velocity 2.8 +/- 0.8 cm/sec, resistance index 0.68
      +/- 0.1), and hypoestrogenic postmenopausal women (diastolic velocity 2.6 +/- 0.9
      cm/sec, resistance index 0.73 +/- 0.08). Significant differences were not seen in
      the ophthalmic artery. In the postmenopausal patients estradiol therapy was
      associated with an increase in diastolic velocity (2.6 +/- 0.9 cm/sec vs 4.1 +/-
      1.6 cm/sec) and a decrease in the resistance index (0.73 +/- 0.08 vs 0.66 +/-
      0.1) in the central retinal artery but not in the ophthalmic artery. CONCLUSIONS:
      The blood velocity and vascular resistance in the cerebral microcirculation
      appear to change according to the phases of a woman's reproductive life. This may
      be related, in part, to estrogen levels, because estradiol vasodilates small
      diameter cerebral vessels in hypoestrogenic postmenopausal women.

PMID- 7726270
TI  - Third stage of labor: analysis of duration and clinical practice.
AB  - OBJECTIVES: Our purpose was to record gestational age-specific data for third
      stage duration of labor, frequencies of retained placentas (undelivered at 30
      minutes), manual removal of the placenta, and hemorrhage. STUDY DESIGN: Included
      were 45,852 singleton deliveries > or = 20 weeks' gestation from 1984 to 1992.
      Odds ratios, 95% confidence intervals, and actuarial life analysis with censoring
      of cases with manual placenta removal were performed. RESULTS: The frequency of
      retained placentas (2.0% overall) was markedly increased among gestations < or =
      26 weeks (odds ratio 20.8, 95% confidence interval 17.1 to 25.4) and < 37 weeks
      (odds ratio 3.0, 95% confidence interval 2.6 to 3.5) compared with term. The
      frequency of manual removal (3.0% overall) was increased among gestations < or =
      26 weeks (odds ratio 9.2, 95% confidence interval 7.5 to 11.4) and < 37 weeks
      (odds ratio 2.8, 95% confidence interval 2.4 to 3.1) compared with term.
      Hemorrhage (3.5% overall) was increased among subjects with manual placenta
      removal (odds ratio 10.4, 95% confidence interval 9.1 to 11.9); hemorrhage was
      also increased among gestations < or = 26 weeks (odds ratio 3.0, 95% confidence
      interval 2.3 to 4.0) and < 37 weeks (odds ratio 1.2, 95% confidence interval 1.01
      to 1.3) compared with term. The frequency of hemorrhage peaked by 40 minutes
      regardless of gestational age. Life-table analysis predicted 90% of placentas
      would spontaneously deliver by 180 minutes for gestations at 20 weeks, 21 minutes
      at 30 weeks, and 14 minutes at 40 weeks; the predicted frequency of retained
      placentas was 42% higher than the recorded incidence. CONCLUSIONS: The duration
      of the third stage decreases and the frequencies of hemorrhage and manual removal
      decrease with increasing gestational age. Hemorrhage was associated with manual
      placental removal. Life-table analysis indicated that manual removal of placentas
      shortened the duration of the third stage of labor, especially among preterm
      deliveries. A prospective trial is needed to determine whether manual placental
      removal can reduce hemorrhage among prolonged third stages.

PMID- 7726271
TI  - Gynecologic and obstetric aspects of Gaucher's disease: a survey of 53 patients.
AB  - OBJECTIVE: We report our experience on the gynecologic and obstetric features of
      53 female patients with Gaucher's disease. STUDY DESIGN: Each patient was
      interviewed for a detailed medical history, and all underwent a complete physical
      examination and laboratory work-up. RESULTS: Delay of puberty onset was
      encountered in two thirds of the patients without subsequent infertility. Heavy
      menstrual bleeding was a major problem and was best treated with low-dose oral
      contraceptives. Of the 102 spontaneous pregnancies' 25 (24.5%) ended in
      spontaneous first-trimesters abortions; 72 continued beyond the twenty-second
      week. Nine patients (27.7%) were diagnosed as having Gaucher's disease during
      their first pregnancies. Aggravation of thrombocytopenia and anemia were
      prominent features, but antepartum blood transfusion was not required. Early
      postpartum hemorrhage and fever were increased after both cesarean and vaginal
      deliveries. Development of bone crisis in seven women during the third trimester
      and early postpartum periods recurred in subsequent pregnancies. Genotypes had
      not influenced the gynecologic or obstetric manifestations. CONCLUSIONS:
      Gynecologic and obstetric complications play a significant role in this patient
      population, representing an additional burden to female patients with Gaucher's
      disease.

PMID- 7726272
TI  - Blindness associated with preeclampsia and eclampsia.
AB  - OBJECTIVE: Over a 14-year period at Parkland Hospital, the clinical courses of 15
      women with severe preeclampsia or eclampsia were further complicated by
      blindness. Our purpose is to describe their management and outcome, as well as to
      offer insight to the pathophysiologic characteristics of blindness complicating
      pregnancy-induced hypertension. STUDY DESIGN: Prospective ascertainment of women
      with blindness and pregnancy-induced hypertension was done. These cases were
      managed according to the standardized preeclampsia-eclampsia regimen used at our
      hospital since 1955. Briefly, this regimen includes magnesium sulfate given
      intramuscularly to prevent or control seizures, hydralazine to lower dangerously
      elevated blood pressure, intravenous fluid restriction, and delivery. RESULTS:
      There were 15 women with blindness that persisted from 4 hours to 8 days; it
      subsequently resolved completely in all. Of the 13 women who underwent computed
      tomography, 8 had low-density areas localized predominantly in the occipital
      lobes. Five of these 13 subsequently underwent magnetic resonance imaging and 2
      showed corresponding hyperintense lesions in the occipital areas. CONCLUSIONS: On
      the basis of previously published experiences with computed tomography in women
      with eclampsia, as well as the experiences described here, we conclude that
      cortical blindness associated with preeclampsia-eclampsia results from petechial
      hemorrhages and focal edema in the occipital cortex. These lesions are likely
      stimulated by disparity in cerebral regional blood flow that is characterized by
      vasospasm and diminished flow primarily affecting the posterior circulation.

PMID- 7726273
TI  - A comparison between detailed and simple histories in the diagnosis of genital
      herpes complicating pregnancy.
AB  - OBJECTIVE: All women seropositive for herpes simplex virus-2 are at risk for
      asymptomatic viral shedding at the onset of labor and neonatal transmission of
      the virus. Unfortunately, only 20% to 35% of seropositive adults give a history
      consistent with genital herpes. We evaluated whether more detailed questioning
      during pregnancy might elucidate symptoms predictive of seropositivity and
      therefore better identify women at risk for herpes simplex virus shedding at
      delivery. STUDY DESIGN: During pregnancy 201 randomly selected women were asked
      in-depth questions about recurrent genital symptoms and whether they "currently
      have or have ever had genital herpes." An assessment was made whether the patient
      had a history compatible with genital herpes. This assessment and the "yes/no"
      history of genital herpes obtained by physicians at the initial prenatal visit
      were both compared with herpes simplex virus serologic studies by Western blot.
      RESULTS: Of 201 patients interviewed, 177 gave no history of genital herpes. Of
      these, 30.4% were seropositive for herpes simplex virus-2. Detailed histories on
      these 177 patients indicated that among the 159 subjects without suggestive
      symptoms or with somewhat suggestive symptoms the corresponding rates of
      seropositivity were 28% and 30%. Among the 18 (10.2%) subjects with highly
      suggestive symptoms, only 50% were seropositive. The positive predictive values
      for recurrent genital symptoms to predict herpes simplex virus-2 seropositivity
      ranged from 30% to 57%. CONCLUSION: A detailed history of genital symptoms is no
      better at identifying an herpes simplex virus-2 seropositive patient than is
      simply asking if she has ever had genital herpes. Serologic screening is a more
      accurate method of identifying women with past genital herpes or those who are at
      risk for acquiring genital herpes during pregnancy.

PMID- 7726274
TI  - Placental passage of the oxytocin antagonist atosiban.
AB  - OBJECTIVE: We wanted to determine the degree of placental transfer of atosiban
      (Antocin), an oxytocin antagonist, in pregnant women at term. We also assessed
      the effects of the infusion on umbilical cord blood gases at birth and the
      maternal hematocrit drop after cesarean section. STUDY DESIGN: Eight women
      undergoing elective cesarean section at term were studied. Each received an
      infusion of 300 micrograms/min of atosiban over 208 to 443 minutes; the infusion
      was continued up to the time of cord clamping. Uterine vein and umbilical blood
      samples were obtained simultaneously. They were assayed by specific
      radioimmunoassay. Cord blood gases were obtained and compared with those from a
      control group of women undergoing elective cesarean section. RESULTS: The mean
      (+/- SD) maternal uterine vein concentration was 331.9 +/- 42.9 ng/ml, compared
      with 42 +/- 13 ng/ml in the umbilical vein (p < 0.05). The mean maternal/fetal
      was 12 +/- 0.03, which was not affected by the length of infusion. There was no
      significant difference in the hematocrit drop between the cesarean delivery
      groups: 5.9 +/- 0.4 for the control group versus 5.8 +/- 1.1 for the atosiban
      group (p > 0.1). The mean cord pH was 7.27 for the atosiban group versus 7.27 for
      the control group (n = 141) (p > 0.1). One year follow-up of the infants (n = 7)
      was normal. CONCLUSIONS: Our results show minimal placental transfer of atosiban.
      Drug levels did not increase with longer infusions, and no effect was seen on
      umbilical cord gases. Administration of atosiban even at high doses up to the
      time of delivery did not increase maternal blood loss at cesarean section.

PMID- 7726275
TI  - Pregnancy outcome after gestational exposure to amiodarone in Canada.
AB  - OBJECTIVE: Our purpose was to quantitate the risk of perinatal thyroid
      dysfunction and other amiodarone-induced adverse effects among infants exposed in
      utero to amiodarone. STUDY DESIGN: A historic cohort study of gestational
      exposure to amiodarone was conducted by contacting Canadian cardiac
      electrophysiologists. RESULTS: Twelve cases were identified. Of six with first
      trimester exposure, one child had congenital nystagmus with synchronous head
      titubation. There was one case each of transient neonatal hypothyroidism (9%) and
      hyperthyroidism (9%). A fourth child, exposed to amiodarone from 20 weeks'
      gestation, had developmental delay, hypotonia, hypertelorism, and micrognathia.
      Four small-for-gestational-age infants were also exposed to beta-blockers, which
      in addition to maternal cardiac disease, have been recognized to cause growth
      restriction. beta-Blockers may also have contributed to bradycardia in one of the
      three fetuses in whom this was observed. CONCLUSIONS: Gestational exposure to
      amiodarone may be complicated by perinatal hypothyroidism or hyperthyroidism and
      possibly neurologic abnormalities, intrauterine growth retardation or fetal
      bradycardia. Concomitant beta-blocker therapy should probably be avoided. Full
      neonatal thyroid function tests and developmental follow-up are recommended.

PMID- 7726276
TI  - Resident data collection: do the numbers add up?
AB  - OBJECTIVES: Our purpose was to investigate methods for standardization of data
      collection across residency training programs in obstetrics and gynecology. STUDY
      DESIGN: A survey was developed and sent to all accredited residency programs in
      the United States and Canada. It assessed each program's current data collection
      method and whether the system could track discrepancies, account for completeness
      of data, or collect primary care data. The second part of the survey was designed
      to assess program director consistency in assignment of resident responsibility.
      RESULTS: In 78.5% of programs residents used a paper-based system. Only 27.1% and
      31.3% of the residency programs, respectively, had systems for resolving resident
      responsibility conflicts or determining accuracy percentages. Few (8.3%) program
      directors were able to collect primary care data. There were wide variations
      among program directors in assignment of resident responsibility in the simulated
      cases, indicating different interpretations of Residency Review Committee
      reporting criteria. CONCLUSIONS: Most resident data systems in use do not promote
      or require standardization of data collection; therefore comparisons between
      programs would be difficult. The ideal system would be flexible, require
      standardization of data collection, enable direct transfer to Residency Review
      Committee forms, be translatable to any residency program, and allow meaningful
      intraprogram and interprogram comparisons.

PMID- 7726277
TI  - A treatise of midwifry, in three parts.

PMID- 7726278
TI  - Risk of endometrial hyperplasia progressing to cancer.

PMID- 7726279
TI  - Female genital mutilation.

PMID- 7726280
TI  - On prolonged pregnancy.

PMID- 7726281
TI  - Neurobiology of cocaine binging in pregnancy.

PMID- 7726282
TI  - Angina pectoris and myocardial infarction with the use of leuprolide acetate.

PMID- 7726283
TI  - Ovarian cysts in tamoxifen-treated premenopausal women with breast cancer--a
      management dilemma.

PMID- 7726284
TI  - Posterior presentation revisited.

PMID- 7726285
TI  - Accuracy of oscillometric blood pressure measurements in preeclampsia.

PMID- 7726286
TI  - Validity of the postcoital test.

PMID- 7726287
TI  - Automated blood pressure measurement in pregnancy.

PMID- 7726288
TI  - Death knell for the contraction stress test?

PMID- 7726289
TI  - Epidemiology and clinical pathophysiology of condylomata acuminata.

PMID- 7726290
TI  - Clinical manifestations and modern management of condylomata acuminata: a
      dermatologic perspective.

PMID- 7726291
TI  - Management of condylomata acuminata with Alferon N injection, interferon alfa-n3
      (human leukocyte derived).

PMID- 7726292
TI  - Average menarcheal age of higher socioeconomic status urban Cape coloured girls
      assessed by means of status quo and recall methods.
AB  - The age of the onset of menstruation has been determined for the urban middle
      class Cape Coloured population. From 1987 to 1992 data were collected from 857
      girls aged 8 to 20 years attending primary and secondary schools in Cape Town.
      The schools were specifically selected for the highest socioeconomic status (SES)
      of pupils' parents. Three-quarters of parents fell into the higher three
      categories of the 5-category SES standard. Girls were interviewed with respect to
      their menarcheal status and those who were postmenarcheal were also asked to
      report when they had started to menstruate. The probit analysis of the status quo
      data yielded average of 12.61 years and a standard deviation (s) of 1.25 years.
      The retrospective method was applied only to recall data of 258 girls falling
      into fully postmenearcheal categories (16-20 years). It yielded an average of
      12.75 (s = 1.32), insignificantly different from that obtained from the probit
      analysis. The menarcheal age of higher SES Cape Coloured girls is significantly
      lower than that of white girls in Cape Town (13.30 years) and much lower than
      that of any group of black South African girls. It falls close to the lower limit
      of the range reported worldwide. Body heights, weights, and Body Mass Index
      indicate good growth status of girls studied.

PMID- 7726294
TI  - Heel contact as a function of substrate type and speed in primates.
AB  - In this report we provide detailed data on the patterns and frequency of heel
      contact with terrestrial and arboreal supports in primates. These data can help
      resolve the question of whether African apes and humans are uniquely
      "plantigrade" (Gebo [1992] Am. J. Phys. Anthropol. 89:29-58; Gebo [1993a] Am. J.
      Phys. Anthropol. 91:382-385; Gebo [1993b] Postcranial Adaptation in Nonhuman
      Primates), or if plantigrady is common in other primates (Meldrum [1993] Am. J.
      Phys. Anthropol. 91:379-381). Using biplanar and uniplanar videotapes, we
      recorded the frequency and timing of heel contact for a variety of primates (32
      species) walking on the ground and on simulated arboreal supports at a range of
      natural speeds. Our results indicate that Pongo as well as the African apes
      exhibit a "heel-strike" at the end of swing phase. Ateles and Hylobates make heel
      contact on all supports shortly after mid-foot contact, although spider monkeys
      do so only at slow or moderate speeds. Data available from uniplanar videotapes
      suggest that this pattern occurs in Alouatta and Lagothrix as well. No other New
      or Old World monkey or prosimian in this study made heel contact during
      quadrupedalism on any substrate. Thus, heel contact occurs in all apes and
      atelines, but only the great apes exhibit a heel-strike. We suggest that heel
      contact with the substrate is a by-product of an active posterior weight-shift
      mechanism involving highly protracted hindlimbs at touchdown. Force plate studies
      indicate that this mechanism is most extreme in arboreally adapted primate
      quadrupeds walking on arboreal supports. Although heel contact and heel-strike
      may have no evolutionary link, it is possible that both patterns are the result
      of a similar weight shift mechanism. Therefore, the regular occurrence of heel
      contact in a variety of arboreal primates, and the absence of a true
      biomechanical link between limb elongation, heel contact, and terrestriality,
      calls into question the claim that hominid foot posture was necessarily derived
      from a quadrupedal terrestrial ancestor.

PMID- 7726293
TI  - Anthropometric variation and the population history of Ireland.
AB  - Genetic variation among human populations can reflect a combination of
      contemporary patterns of gene flow and genetic drift as well as long-term
      population relationships due to population history. We examine the likely impact
      of past history and contemporary structure on the patterns of anthropometric
      variation among 31 counties in Ireland (made up of the two nations of the
      Republic of Ireland and Northern Ireland). Data for 17 anthropometric measures
      and parent-offspring migration on 7,214 adult Irish males were taken from the
      large data set originally collected by Dupertuis and Dawson in the mid-1930s
      (Hooton et al., 1955). Patterns of genetic similarity among 31 counties were
      assessed using R matrix methods that allow estimation of minimum genetic
      distances. These distances were compared to distances reflecting history,
      geography, and migration using matrix permutation methods. The results indicate
      that among-group variation in Ireland reflects past population history to a much
      greater extent than contemporary patterns of migration and population size. The
      midland counties are distinct from other populations, and their history suggests
      greater genetic input from early Viking invasions. A second major pattern in
      biological variation is a longitudinal gradient separating western and eastern
      counties. This gradient appears related to patterns of early settlement and/or a
      concentration in the east of later immigrants, particularly from England.
      Comparison of regional means with published data for several other European
      nations confirms these hypotheses.

PMID- 7726295
TI  - Subvertical grooves of interproximal facets in Neandertal posterior teeth.
AB  - Subvertical grooves, located on the interproximal facets of most Neandertal
      posterior teeth, are less frequently noted on the teeth of other hominids,
      including modern humans. These grooves, 0.1-0.5 mm in width, are strictly
      localized within the facet area. Scanning electron microscopic (SEM) examination
      of grooves present on Neandertal teeth from Caverna delle Fate (Liguria, Italy)
      and Genay (Cote d'Or, France) demonstrated that they were produced during the
      life of these individuals. Characteristics of the groove surface suggest an
      erosion-abrasion mechanism of formation. These grooves, which developed in parts
      of the dentition exposed to marked stress, originated in areas characterized by
      changes in the orientation of enamel prism bundles (i.e., Hunter-Schreger bands).
      Observations carried out on modern human molars showed a subvertical disposition
      of these bands near interproximal ridges facilitating subvertical microfractures.
      Possible correlations between enamel structure, masticatory stress, and
      interproximal groove formation in Neandertals are discussed.

PMID- 7726296
TI  - Human (Homo sapiens) and chimpanzee (Pan troglodytes) share similar ancestral
      centromeric alpha satellite DNA sequences but other fractions of heterochromatin
      differ considerably.
AB  - The euchromatic regions of chimpanzee (Pan troglodytes) genome share
      approximately 98% sequence similarity with the human (Homo sapiens), while the
      heterochromatic regions display considerable divergence. Positive heterochromatic
      regions revealed by the CBG-technique are confined to pericentromeric areas in
      humans, while in chimpanzees, these regions are pericentromeric, telomeric, and
      intercalary. When human chromosomes are digested with restriction endonuclease
      AluI and stained by Giemsa (AluI/Giemsa), positive heterochromatin is detected
      only in the pericentromeric regions, while in chimpanzee, telomeric,
      pericentromeric, and in some chromosomes both telomeric and centromeric, regions
      are positive. The DA/DAPI technique further revealed extensive cytochemical
      heterogeneity of heterochromatin in both species. Nevertheless, the fluorescence
      in situ hybridization technique (FISH) using a centromeric alpha satellite
      cocktail probe revealed that both primates share similar pericentromeric alpha
      satellite DNA sequences. Furthermore, cross-hybridization experiments using
      chromosomes of gorilla (Gorilla gorilla) and orangutan (Pongo pygmaeus) suggest
      that the alphoid repeats of human and great apes are highly conserved, implying
      that these repeat families were present in their common ancestor. Nevertheless,
      the orangutan's chromosome 9 did not cross-hybridize with human probe.

PMID- 7726297
TI  - Hominid fossil sample from Kanjera, Kenya: description, provenance, and
      implications of new and earlier discoveries.
AB  - Anatomically modern hominids were first collected from Kanjera, Kenya, by L.S.B.
      Leakey in the 1930s. Their apparent association with an archaic fauna was quickly
      challenged, throwing their age into doubt. Further unpublished hominid fragments
      were collected in 1974, 1975, 1981, and 1987. We review the context and
      morphology of the entire hominid sample. A minimum number of five individuals is
      represented by both cranial and postcranial elements. Several individuals have
      thickened cranial vaults, a characteristic originally thought to reflect their
      great antiquity. Vault thickening resulted from diploic expansion and may have
      been a response to acquired or inherited anemia. The entire hominid sample
      postdates the Kanjera Formation, deposited from the early into the middle
      Pleistocene. Most of the sample was derived from the black cotton soil capping
      the stratigraphic column. The morphology and context of the Kanjera hominids is
      consistent with human skeletal remains from nearby Holocene sites. Hominid 3 was
      probably an intrusive burial into an early Pleistocene bed.

PMID- 7726298
TI  - Habitat, annual, and seasonal effects on positional behavior in red colobus
      monkeys.
AB  - Positional behavior in adult red colobus monkeys (Colobus badius) was examined in
      a variety of ecological contexts. Using a focal-animal methodology, we assessed
      how data collected by different observers, in different years, in different
      seasons, and in different forests affected estimates of positional behavior. In
      all, 23,000 bouts were recorded. Variation in frequency is greatest in the common
      behaviors, especially arboreal quadrupedalism. Significant behavioral differences
      occur more often in the context of different forests than in annual or seasonal
      comparisons. The activity of feeding exhibits the largest frequency changes
      across positional behavior and ecological context. In all, red colobus monkeys
      exhibit substantial amounts of flexibility in positional behavior across
      different ecological contexts.

PMID- 7726299
TI  - Reliability of reliability coefficients in the estimation of asymmetry.
AB  - Although promising to provide insight into the interaction between genotype and
      environment, investigations into fluctuating asymmetry suffer from a lack of
      standardization in the reporting of measurement error. In the present paper we
      show, using both anthropometric and odontometric data, that the use of the
      reliability coefficient calculated for a bilateral measurement provides no
      indication of the reliability of the corresponding asymmetry estimate, because
      reliability of asymmetry depends on the relationship between measurement error
      and the difference between sides. Thus, we suggest that future investigations
      either provide reliability coefficients for asymmetry estimates specifically, or
      use methods that account for measurement error.

PMID- 7726303
TI  - Images in neuroscience. The hippocampus in epilepsy.

PMID- 7726302
TI  - Imaging the mind: magnetic resonance spectroscopy and functional brain imaging.

PMID- 7726301
TI  - Third molar impactions in early hominids.

PMID- 7726300
TI  - Brief communication: cortical remodeling data are affected by sampling location.
AB  - It has been argued that techniques for estimating adult age-at-death from
      cortical histology are deleteriously affected by sampling location. This study
      uses nine complete femoral midshaft cross-sections to test the effect of sampling
      site on measurement of a standard histological variable, percent remodeled bone.
      Circumferential periosteal fields from four anatomically defined locations
      (anterior, posterior, medial, lateral) and four mechanically defined locations
      (maximum and minimum moments of area) were evaluated. Locations deviating from
      the periosteal surface toward the endosteal surface were also compared.
      Significant differences were found for both location and field placement. The
      anatomical axes exhibited greater variability than the mechanical axes, in
      particular the anterior location, a standard sampling site for age-at-death
      estimation techniques. More endosteal fields tended to show elevated levels of
      percent remodeled bone. This study demonstrates that circumferential and radial
      sampling locations are important considerations in deriving and applying
      predictive equations based on cortical remodeling.

PMID- 7726304
TI  - Effect of therapeutic innovation on perception of disease and the doctor-patient
      relationship: a history of general paralysis of the insane and malaria fever
      therapy, 1910-1950.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of therapeutic
      innovation on the interpersonal style of physicians by using the historical
      example of the treatment of general paralysis of the insane by malaria fever
      therapy. METHOD: The study employed historical qualitative and descriptive
      methods to analyze medical and popular literature and medical records. These
      medical records were from a single institution and contained verbatim transcripts
      of patient interviews and doctors' conferences. The author examined records of
      patients diagnosed with neurosyphilis from the periods before (1910-1928) and
      after (1928-1950) the introduction of malaria fever therapy. RESULTS: Before the
      introduction of malaria fever therapy, physicians saw their neurosyphilitic
      patients as "hopeless," "immoral," and "stupid" paretics--objects to be acted
      upon, a view consistent with the cultural belief that syphilitic patients were
      sinful and depraved. After the introduction of malaria fever therapy, doctors
      wrote more positively and empathically about their neurosyphilitic patients,
      allowing patients to become active participants in their therapeutic regimens.
      Patients with neurosyphilis voluntarily sought admission specifically for fever
      therapy, seeing the asylum as a place of cure rather than as an institution of
      confinement. CONCLUSIONS: This history illustrates that biological therapies can
      powerfully affect physicians' perceptions of patients and need not remove them
      from patients' subjective experiences. Instead, biological treatments may enhance
      physicians' ability to empathize with their patients' suffering.

PMID- 7726305
TI  - Proton magnetic resonance spectroscopy investigation of hyperventilation in
      subjects with panic disorder and comparison subjects.
AB  - OBJECTIVE: The purpose of this study was to investigate differential effects of
      hyperventilation on brain lactate in patients with panic disorder and comparison
      subjects as a possible mechanism for explaining previous observations of an
      excess rise in brain lactate among panic disorder subjects during lactate
      infusion. METHOD: Seven treatment-responsive patients with panic disorder and
      seven healthy comparison subjects were studied with proton magnetic resonance
      spectroscopy to measure brain lactate during controlled, voluntary
      hyperventilation over a period of 20 minutes. Hyperventilation was regulated with
      the use of capnometry to maintain end-tidal PCO2 at approximately 20 mm Hg during
      the period of hyperventilation. Blood lactate was measured prior to and at the
      end of hyperventilation. RESULTS: At baseline the two groups had similar brain
      lactate levels. Panic disorder subjects exhibited significantly greater rises in
      brain lactate than comparison subjects in response to the same level of
      hyperventilation. Blood lactate levels before and after 20 minutes of
      hyperventilation were not significantly different between groups. CONCLUSIONS:
      Controlled hyperventilation increases brain lactate and does so
      disproportionately in subjects with panic disorder. This increase in brain
      lactate may result from decreased cerebral blood flow due to hypocapnia, and
      individuals with panic disorder may have greater sensitivity to this regulatory
      mechanism.

PMID- 7726307
TI  - Treatment of panic disorder with agoraphobia: comparison of fluvoxamine, placebo,
      and psychological panic management combined with exposure and of exposure in vivo
      alone.
AB  - OBJECTIVE: The purpose of this comparative outcome study was to investigate
      whether the effects of exposure in vivo treatment for panic disorder with
      agoraphobia could be enhanced by adding interventions specifically for panic
      attacks before the start of exposure treatment. The additional effect of two
      types of treatment for panic attacks--pharmacological (fluvoxamine) and
      psychological (repeated hyperventilation provocations and respiratory training)-
      was examined. Thus, the combined treatment of panic interventions with exposure
      in vivo could be compared to exposure in vivo alone. METHOD: Ninety-six patients
      were randomly assigned to four treatment conditions: double-blind, placebo
      controlled fluvoxamine followed by exposure in vivo, psychological panic
      management followed by exposure, and exposure in vivo alone. Outcome was assessed
      by self-report measures, a standardized multitask behavioral avoidance test, and
      continuous monitoring of panic attacks. Seventy-six patients completed the study.
      RESULTS: All four treatments were effective and resulted in a significant
      decrease of agoraphobic avoidance. Moreover, the combination of fluvoxamine and
      exposure in vivo demonstrated efficacy superior to that of the other treatments
      and had twice as large an effect size (difference between pre- and posttreatment
      scores) on self-reported agoraphobic avoidance. The other treatments did not
      differ among each other in effectiveness. CONCLUSIONS: Results of the study
      indicate that the short-term outcome of exposure in vivo treatment can be
      enhanced by adding fluvoxamine treatment. Psychological panic management combined
      with exposure was not superior to exposure alone of equal duration.

PMID- 7726308
TI  - Effect of chloride or glucose on the incidence of lactate-induced panic attacks.
AB  - OBJECTIVE: This study was designed to test the hypothesis that the addition of
      chloride to a lactate infusion would reduce the frequency of panic attacks.
      METHOD: The subjects included 14 healthy volunteers and 20 patients meeting the
      DSM-IV criteria for panic disorder. All subjects received an infusion of lactate
      dissolved in 0.9% sodium chloride and an infusion of lactate dissolved in 5%
      dextrose in water on separate days in a random-order, double-blind procedure.
      Blood pressure, heart rate, and panic symptoms were measured at 3-minute
      intervals during the infusions. The occurrence of panic attacks was ascertained
      through the subjects' reports of losing control, panicking, or "going crazy" and
      the presence of at least four Research Diagnostic Criteria symptoms of a panic
      attack. RESULTS: Fifteen (75%) of the patients with panic disorder reported a
      panic attack during one of the infusions or both; no healthy volunteers had a
      panic attack. The patients with panic disorder were significantly more likely to
      have a panic attack during the lactate/sodium chloride infusion than during the
      infusion of lactate/5% dextrose in water. The number of panic attack symptoms
      reported at 3-minute intervals did not differ between the two types of infusion.
      CONCLUSIONS: The coadministration of glucose resulted in a reduced sensitivity to
      the panicogenic effects of lactate. The hypothesis that adding chloride to the
      infusion would reduce the frequency of lactate-induced panic attacks was not
      supported.

PMID- 7726309
TI  - Gender differences in onset of illness, treatment response, course, and biologic
      indexes in first-episode schizophrenic patients.
AB  - OBJECTIVE: Gender differences in onset of illness, response to treatment, course,
      and biologic measures have been consistently reported in patients with chronic
      schizophrenia. Patients with first-episode schizophrenia were examined to
      determine whether gender differences also occur in these patients. METHOD: Fifty
      four neuroleptic-naive schizophrenic patients (29 men and 25 women) were studied
      beginning in an initial stage of the first hospitalization for psychosis while
      undergoing treatment with a standardized medication regimen. Before antipsychotic
      drug treatment and during 1 year of follow-up each patient was rated on the
      Schedule for Affective Disorders and Schizophrenia--Change Version (psychosis and
      disorganization items), Scale for the Assessment of Negative Symptoms, Clinical
      Global Impression, modified Simpson Tardive Dyskinesia Scale, and Simpson-Angus
      Rating Scale for extrapyramidal side effects. Methylphenidate challenge testing
      was done at study entry. Plasma neuroleptic, homovanillic acid (HVA), and
      prolactin levels were determined weekly for the first 6 weeks. RESULTS: The
      female schizophrenic patients had a later onset and better treatment response
      than the men. Plasma HVA levels at baseline and week 1 and changes in prolactin
      levels from baseline to weeks 1 through 6 were greater among the women.
      CONCLUSIONS: Gender differences in onset and degree of treatment response in
      first-episode schizophrenic patients are similar to those of chronic patients and
      are apparent at early stages of the illness. The greater pharmacologic
      responsivity of the female patients, as indicated by the neuroendocrine results,
      is consistent with the gender difference in degree of symptom improvement with
      medication.

PMID- 7726310
TI  - Effects of diagnosis, laterality, and gender on brain morphology in
      schizophrenia.
AB  - OBJECTIVE: Structural neuroimaging and neuropathological studies have
      demonstrated a variety of aspects of brain morphology that appear to distinguish
      schizophrenic patients from comparison subjects (diagnostic effects), a
      predominance of left-sided pathology (laterality effects), and a greater
      likelihood of brain abnormality among males (gender effects). However, findings
      have been inconsistent across studies, perhaps reflecting limited power due to
      small study group sizes. The goal of this study was to examine diagnostic,
      laterality, and gender effects of brain morphology as assessed by magnetic
      resonance imaging in a large, carefully evaluated group of schizophrenic and
      comparison subjects. METHOD: One hundred two patients with schizophrenia (DSM-III
      R) (70 men and 32 women) and 87 normal comparison subjects, chosen to be
      equivalent to the patients in terms of familial socioeconomic background,
      underwent magnetic resonance imaging with a 1.5-tesla scanner. All regions of
      interest were outlined manually by an experienced technician on all slices in
      which they were visualized. Region of interest volumes were compared across
      groups, and age, sex, and stature were controlled. RESULTS: Schizophrenic
      patients were found to have larger lateral and third ventricles and smaller
      thalamic, hippocampal, and superior temporal volumes than comparison subjects. No
      significant differences were demonstrated for intracranial, cerebral, cerebellar,
      temporal lobe, caudate nuclei, or temporal horn volumes. There were no
      significant Laterality by Diagnosis effects and no significant Gender by
      Diagnosis effects for any of the regions of interest. CONCLUSIONS: Many, but not
      all, of the hypotheses informed by earlier studies regarding diagnostic effects
      were confirmed, while hypotheses regarding gender and laterality interactions
      with diagnosis were not supported.

PMID- 7726306
TI  - Imipramine treatment of panic disorder with agoraphobia: dose ranging and plasma
      level-response relationships.
AB  - OBJECTIVE: The aim of this study was to characterize the specific effects of
      imipramine in the treatment of panic disorder with agoraphobia and to delineate
      dose-response and possibly plasma level-response relationships. METHOD: Eighty
      patients with panic disorder with agoraphobia were randomly assigned, for an 8
      week, double-blind dose-ranging trial, to placebo or to a weight-adjusted dose of
      imipramine: (low) 0.5 mg/kg per day, (medium) 1.5 mg/kg per day, or (high) 3.0
      mg/kg per day. Plasma levels of imipramine and N-methylimipramine, patients' and
      clinicians' ratings of panic and phobic symptoms, and response to treatment
      according to operationalized criteria were ascertained after 4 and 8 weeks.
      RESULTS: Rates of dropouts due to drug side effects were 6%, 15%, and 36% in the
      low-, medium-, and high-dose groups, respectively; 63 patients completed the
      study. Compliance with the drug regimen was high. There was a positive dose
      response relationship, with significant group differences involving primarily the
      high- and medium-dose groups versus the placebo group. There were no significant
      differences between the placebo and low-dose groups or the medium- and high-dose
      groups. For phobias, the best total drug plasma level was in the range of 110-140
      ng/ml; higher levels had a detrimental effect. For panic, the probability of
      response increased quickly with greater plasma levels and then tapered off, with
      no improvement at levels beyond 140 ng/ml. CONCLUSIONS: The results provide
      strong evidence that imipramine has specific, clinically significant effects in
      this disorder, with practical implications for target doses and optimal plasma
      concentrations, and suggest that different mechanisms underlie the drug's
      antipanic and antiphobic effects.

PMID- 7726311
TI  - Reversal of asymmetry of the planum temporale in schizophrenia.
AB  - OBJECTIVE: The planum temporale is intimately involved in the generation and
      understanding of language and has been suggested to be a key area affected in
      schizophrenia. To explore temporal lobe abnormalities in schizophrenia, the
      authors measured the planum temporale, a normally asymmetric area lying on the
      superior part of the temporal lobe, in schizophrenic patients. METHOD: High
      resolution magnetic resonance imaging (MRI) scans were obtained for 14 right
      handed schizophrenic patients and 14 healthy comparison subjects individually
      matched for age, sex, handedness, race, and parental socioeconomic status. The
      surface area of the planum temporale was measured by using MRI reconstruction
      techniques. RESULTS: There was striking reversal of the normal asymmetry (left
      larger than right) in planum temporale surface area in 13 of the schizophrenic
      patients but in only two of the comparison subjects. However, Heschl's gyrus
      (primary sensory cortex), which served as an anatomically contiguous
      nonheteromodal cortical comparison region, showed no difference between the left
      and right sides in either group. Severity of thought disorder in the patients was
      related to asymmetry. CONCLUSIONS: This is a clear demonstration of a reversal of
      expected symmetry in the brains of right-handed schizophrenic patients, which
      involves a region of key importance in normal human behavior. The nature of the
      abnormality strongly suggests that schizophrenia is a neurodevelopmental
      disorder.

PMID- 7726313
TI  - Prospective clinicopathologic studies of schizophrenia: accrual and assessment of
      patients.
AB  - OBJECTIVE: The purpose of this study was to characterize the neuropsychiatric
      profile of elderly patients with schizophrenia and establish a patient registry
      for prospective ante-mortem and post-mortem studies. METHOD: Medical records of
      all chronically institutionalized patients in eight state hospitals who were over
      the age of 65 and had a chart diagnosis of schizophrenia (N = 528) were reviewed.
      Of the potential subjects, 192 were excluded because of clinical histories
      inconsistent with a diagnosis of schizophrenia, 56 because of insufficient
      information to establish a psychiatric diagnosis, and 122 because of family
      members' refusal to give consent for autopsy in the event of death. To date, 81
      of the remaining 158 patients have undergone neuropsychiatric evaluation with
      standard assessment instruments. RESULTS: Mini-Mental State scores of the 81
      patients indicated severe dementia, and Functional Assessment Scale scores showed
      that patients required assistance with activities of daily living. All patients
      were rated as severely ill on the Brief Psychiatric Rating Scale. Ratings on the
      Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of
      Positive Symptoms indicated a predominance of negative symptoms over positive. Of
      30 patients who have died to date, research autopsies have been conducted on 26.
      CONCLUSIONS: Establishing a well characterized, prospective patient registry for
      clinicopathologic studies of schizophrenia is feasible but labor intensive.
      Diagnosis of schizophrenia with a high degree of confidence can be achieved by
      means of detailed chart review and assessment of current neuropsychiatric
      functioning with standard rating instruments. These data provide a basis for
      correlations of clinicopathologic factors.

PMID- 7726312
TI  - Clinical and neuropsychological characteristics of patients with late-onset
      schizophrenia.
AB  - OBJECTIVE: The goal was to compare clinical and neuropsychological
      characteristics of patients with late-onset schizophrenia, a poorly studied and
      controversial entity, with those of patients with early-onset schizophrenia and
      normal subjects. METHOD: The authors evaluated 25 patients who met DSM-III-R
      criteria as well as their own research criteria for late-onset schizophrenia
      (i.e., schizophrenia with onset after age 45) and compared them with 39 patients
      with early-onset schizophrenia and 35 normal subjects in this nonepidemiologic
      study. RESULTS: Patients with late-onset schizophrenia were similar to patients
      with early-onset schizophrenia and different from normal subjects on most
      clinical and neuropsychological variables assessed, such as psychopathology,
      family history, childhood social adjustment, and overall pattern of
      neuropsychological impairment. Compared with the early-onset group, the group
      with late-onset schizophrenia had a higher percentage of patients who were ever
      married, a better work history, and a greater frequency of paranoid subtype.
      CONCLUSIONS: These results support the diagnostic validity of schizophrenia with
      onset after the age of 45 years.

PMID- 7726314
TI  - Smaller neuron size in schizophrenia in hippocampal subfields that mediate
      cortical-hippocampal interactions.
AB  - OBJECTIVE: The goal of this study was to characterize the hippocampal formation
      in patients with schizophrenia by measuring neuron density, neuron size, and
      variability of neuronal axis orientation. METHOD: Brain tissue was obtained at
      autopsy from 14 prospectively accrued elderly patients with chronic schizophrenia
      and 10 age-compatible individuals without psychiatric disorder. Eight hippocampal
      regions of interest and two internal control regions (primary motor and visual
      cortices) were identified on Nissl-stained sections. Morphometric measurements
      were made without knowledge of diagnosis by means of a computer-based image
      analysis system. RESULTS: The patients exhibited smaller neuron size in the
      hippocampal regions relative to the control regions, which was significant only
      for the subiculum, CA1, and layer II of the entorhinal cortex. Neuron size in the
      control regions was nearly identical in the two groups. No significant
      differences in neuron density or in variability of neuronal axis orientation were
      identified for any region. There was no correlation between neuron size in any
      area and several potentially confounding variables (age, post-mortem interval,
      neuroleptic exposure, sex, brain hemisphere studied, duration of illness), with
      the exception of a negative correlation with age in layer II of the entorhinal
      cortex. Regression analyses indicated that the findings could not be attributed
      to these age effects. CONCLUSIONS: The subiculum, entorhinal cortex, and CA1 are
      the major subfields of the hippocampal region that maintain the afferent and
      efferent connections of the hippocampus with widespread cortical and subcortical
      targets. The smaller size of neurons in these subfields may reflect the presence
      of structural or functional impairments that disrupt these connections, which in
      turn could have important behavioral sequelae.

PMID- 7726315
TI  - Evaluating the spectrum concept of schizophrenia in the Roscommon Family Study.
AB  - OBJECTIVE: The authors sought to evaluate whether the pattern of schizophrenia
      and related disorders in probands and their relatives can be explained by a
      single underlying continuum of liability to the "schizophrenia spectrum." METHOD:
      In the epidemiologically based Roscommon Family Study, the authors separately
      examined--in siblings, parents, and relatives of index and comparison probands-
      the familial aggregation and coaggregation of five hierarchically defined
      disorders: schizophrenia, schizoaffective disorder, schizotypal/paranoid
      personality disorder, other nonaffective psychoses, and psychotic affective
      illness. A multiple threshold model was fitted to these contingency tables by
      maximum likelihood. RESULTS: The multiple threshold model that constrained
      resemblance to be the same in siblings and parents fit the data well and
      estimated the correlation in liability to schizophrenia spectrum disorders
      between probands and first-degree relatives at 0.36. Parents, however, required
      higher levels of liability to manifest schizophrenia spectrum disorders than
      siblings. While schizophrenia and psychotic affective illness could be clearly
      assigned to the two extremes of the schizophrenia spectrum, the proper ordering
      of schizoaffective disorder, schizotypal/paranoid personality disorder, and other
      nonaffective psychoses could not be unambiguously determined. CONCLUSIONS: These
      results are consistent with the existence of a schizophrenia spectrum in which
      these five disorders are manifestations, of varying severity, of the same
      underlying vulnerability. This vulnerability is strongly transmitted within
      families.

PMID- 7726316
TI  - Examining the validity of DSM-III-R schizoaffective disorder and its putative
      subtypes in the Roscommon Family Study.
AB  - OBJECTIVE: The authors sought to assess whether the DSM-III-R category of
      schizoaffective disorder differs meaningfully from schizophrenia and affective
      illness in clinical features, outcome, and familial psychopathology. In addition,
      the authors evaluated the validity of two proposed subtyping systems for
      schizoaffective disorder: 1) bipolar versus depressive (based on presence or
      absence of a full manic syndrome in the past) and 2) good versus poor
      interepisode recovery. METHOD: In the epidemiologically based Roscommon Family
      Study, index probands with diagnoses of schizophrenia or affective illness were
      selected from a case registry. Personal interviews were conducted with 88% of
      traceable, living probands and 86% of traceable, living first-degree relatives.
      RESULTS: Probands with schizoaffective disorder differed significantly from both
      those with schizophrenia and those with affective illness on lifetime psychotic
      symptoms as well as on outcome and negative symptoms assessed as follow-up.
      Relatives of probands with schizoaffective disorder had significantly higher
      rates of affective illness than relatives of schizophrenic probands and
      significantly higher rates of schizophrenia than relatives of probands with
      affective illness. Probands with bipolar and depressive schizoaffective disorder
      did not differ substantially with respect to psychotic symptoms, negative
      symptoms, outcome, or family history. Schizoaffective disorder probands with good
      interepisode recovery had fewer negative symptoms and a better outcome than those
      with poor recovery, but there were no significant differences in family history.
      Both the epidemiologic and family data are consistent with the hypothesis that
      schizoaffective disorder results from the co-occurrence of a high liability to
      both schizophrenia and affective illness. CONCLUSIONS: On the basis of the
      validators examined, DSM-III-R criteria for schizoaffective disorder define a
      syndrome that differs meaningfully from both schizophrenia and affective illness.
      The division of schizoaffective disorder into bipolar and depressive subtypes
      was, however, not validated. The separation of schizoaffective disorder into
      subtypes based on level of interepisode recovery defined subtypes that differed
      clinically but not with respect to familial psychopathology.

PMID- 7726318
TI  - A case-controlled study of repetitive thoughts and behavior in adults with
      autistic disorder and obsessive-compulsive disorder.
AB  - OBJECTIVE: The purpose of this study was to investigate the types of repetitive
      thoughts and behavior demonstrated by adults with autistic disorder and compare
      them with those of age- and sex-matched adults with obsessive-compulsive
      disorder. METHOD: Fifty consecutive patients admitted to the Yale Adult Pervasive
      Developmental Disorders (Autism) Clinic with a primary diagnosis of autistic
      disorder (DSM-III-R and DSM-IV) completed the symptom checklist of the Yale-Brown
      Obsessive Compulsive Scale. Types of current obsessions and compulsions were
      evaluated. The comparison group consisted of 50 age- and sex-matched adults with
      obsessive-compulsive disorder (without tics) (DSM-III-R and DSM-IV). RESULTS:
      Direct discriminant function analysis showed that the patients with autistic
      disorder could be distinguished from those with obsessive-compulsive disorder on
      the basis of the types of current repetitive thoughts and behavior that they
      demonstrated. Compared to the obsessive-compulsive group, the autistic patients
      were significantly less likely to experience thoughts with aggressive,
      contamination, sexual, religious, symmetry, and somatic content. Repetitive
      ordering; hoarding; telling or asking (trend); touching, tapping, or rubbing; and
      self-damaging or self-mutilating behavior occurred significantly more frequently
      in the autistic patients, whereas cleaning, checking, and counting behavior was
      less common in the autistic group than in the patients with obsessive-compulsive
      disorder. In addition, a specific subset of seven obsessive-compulsive variables
      from the Yale-Brown Obsessive Compulsive Scale symptom checklist was identified
      that reliably predicted membership in the autistic group. CONCLUSIONS: These
      results suggest that the repetitive thoughts and behavior characteristics of
      autism differ significantly from the obsessive-compulsive symptoms displayed by
      patients with obsessive-compulsive disorder. Future studies are warranted to
      assess the treatment response and neurobiological underpinnings of repetitive
      thoughts and behavior in patients with autism and obsessive-compulsive disorder.

PMID- 7726317
TI  - Fluphenazine plasma levels, dosage, efficacy, and side effects.
AB  - OBJECTIVE: The authors sought to determine whether fluphenazine dose or plasma
      level predicts clinical improvement or side effects during acute treatment.
      METHOD: Oral fluphenazine was given in fixed, randomized, double-blind doses (10,
      20, or 30 mg/day) for 4 weeks to 72 inpatients with acute schizophrenic
      exacerbations. Outcome measures included percentage improvement in ratings of
      positive symptoms (hallucinations, delusions, and thought disorder), percentage
      improvement in negative symptoms, and maximum score for extrapyramidal symptoms.
      Response was defined as an improvement in positive symptoms of 40% or more.
      RESULTS: The 42 responders had a shorter duration of illness, less chronic
      course, and lower rate of akathisia. Plasma level and dose did not differentiate
      responders and nonresponders, but they did predict percentage improvement in
      positive symptoms within the responder subgroup. Akathisia was more common and
      extrapyramidal symptoms were more severe at higher plasma levels. CONCLUSIONS:
      Responders showed the greatest improvement at fluphenazine plasma levels above
      1.0 ng/ml and doses above 0.20-0.25 mg/kg per day. Since the literature suggests
      that optimal plasma levels are similar during acute and maintenance treatment,
      monitoring of plasma levels may thus be useful. Conditions for applying the
      "responder-only" analytic strategy in future studies are discussed.

PMID- 7726319
TI  - Tryptophan depletion and attenuation of cue-induced craving for cocaine.
AB  - OBJECTIVE: Although cocaine is a potent serotonin (5-HT) reuptake blocker, the
      role of 5-HT systems in cocaine craving and relapse in humans has been unclear.
      The authors evaluated whether acute reductions in central 5-HT synthesis
      modulated craving for cocaine in cocaine-dependent patients. METHOD: Twenty-five
      cocaine-dependent male inpatients were exposed to cocaine-craving cues while
      their 5-HT levels were lowered and during a placebo condition in a
      counterbalanced, double-blind design. 5-HT levels were reduced by rapidly
      lowering plasma levels of its precursor, tryptophan; tryptophan levels were
      reduced by stimulating protein synthesis with a large drink of amino acids devoid
      of tryptophan. During the placebo condition the patients drank an identical amino
      acid drink containing tryptophan. Craving was induced by exposing patients to
      cocaine paraphernalia and a videotape depicting drug use. Craving was assessed 7
      hours after ingestion of the drink. Visual analog ratings of craving for cocaine
      were administered before and after cue exposure at each test session. RESULTS:
      Patients reported less desire for cocaine stimulated by cue exposure after
      drinking amino acids without tryptophan than they did after drinking placebo. The
      order that tryptophan depletion and placebo tests were performed influenced the
      impact of tryptophan depletion on cue-induced craving. CONCLUSIONS: Serotonergic
      systems modulate cue-induced craving for cocaine, a factor implicated in relapse
      to cocaine use.

PMID- 7726320
TI  - Clinical and phenomenological comparisons of late-onset and early-onset
      depression.
AB  - OBJECTIVE: The authors examined the relationship between age at onset of first
      depressive episode and clinical features in elderly depressed patients. METHOD:
      They used data on age at onset and clinical features in 246 elderly depressed
      patients treated at the National Institute of Mental Health Clinical Research
      Center for the Study of Depression in Later Life, located at Duke University.
      RESULTS: Two variables--loss of interest and number of depressive episodes--were
      related to age at onset in all analyses. CONCLUSIONS: This study confirms the
      hypothesis that apathy is more prominent in late-onset than in early-onset
      depression.

PMID- 7726321
TI  - Psychological dimensions of depression in borderline personality disorder.
AB  - OBJECTIVE: The authors' goal was to test empirically a commonly held assumption
      that the depression in borderline personality disorder is primarily anaclitic.
      METHOD: The Depressive Experiences Questionnaire and the Hamilton Rating Scale
      for Depression were administered to 26 patients with borderline personality
      disorder (16 of whom were depressed) and 12 depressed patients without borderline
      personality disorder. RESULTS: Patients with borderline personality disorder
      showed more self-criticism but did not endorse more anaclitic items than
      depressed patients without borderline personality disorder. CONCLUSIONS: These
      findings suggest that self-criticism is an underemphasized characteristic of
      depression in borderline personality disorder.

PMID- 7726322
TI  - Double-blind, controlled trial of inositol treatment of depression.
AB  - OBJECTIVE: CSF levels of inositol have been reported to be lower than normal in
      depressed subjects. The authors administered inositol to depressed patients in a
      double-blind, controlled trial. METHOD: Under double-blind conditions, 12 g/day
      of inositol (N = 13) or placebo (N = 15) was administered to depressed patients
      for 4 weeks. RESULTS: The overall improvement in scores on the Hamilton
      Depression Rating Scale was significantly greater for inositol than for placebo
      at week 4. No changes were noted in hematology or in kidney or liver function.
      CONCLUSIONS: This may be the first use of the precursor strategy for a second
      messenger rather than a neurotransmitter in treating depression. Although
      inositol had a significant antidepressant effect in this study, replication is
      crucial.

PMID- 7726323
TI  - Correlates of stress reactivity in patients with bipolar disorder.
AB  - OBJECTIVE: The authors examined individual differences in stress reactivity as
      well as whether features of the illness itself or psychological characteristics
      differentiate between patients with bipolar disorder who are highly stress
      reactive and those who are not. METHOD: They assessed stressors and bipolar
      episodes in 58 patients with bipolar disorder followed for at least 1 year.
      RESULTS: Not only did stress level predict relapse, so did personality variables
      such as introversion and obsessionality and their interaction with stress. Number
      of previous episodes of bipolar illness, however, did not affect stress response.
      CONCLUSIONS: These results are not consistent with the view that episodes of
      bipolar disorder become increasingly independent of stressors after initial
      episodes. However, psychological traits may affect reactivity to stressors.

PMID- 7726324
TI  - Season of birth and autistic disorder in Israel.
AB  - OBJECTIVE: Variations in month of birth were examined in patients with infantile
      autism to test the hypothesis that birth in a particular month may be a risk
      factor for this disorder. METHOD: Data for autistic patients registered with the
      National League for Autism in Israel (N = 188) during the years 1964-1986 were
      compared with data on monthly distribution of live births in Israel for the
      corresponding period. RESULTS: After risk ratio estimates were computed for
      children born with infantile autism for each month, a significant increase was
      observed for children born in March and August. This association was true for
      each year throughout the study. An additional finding was a significantly higher
      rate of birth of autistic children in the years 1970-1976. CONCLUSIONS: This
      study, although made in a different climatic area than three earlier studies,
      further emphasizes the earlier findings that March and August births are a risk
      factor for development of autistic disorder.

PMID- 7726325
TI  - SIADH associated with sertraline therapy.

PMID- 7726326
TI  - SIADH associated with fluoxetine and sertraline therapy.

PMID- 7726328
TI  - Sertraline in the treatment of social phobia.

PMID- 7726327
TI  - Shock-like sensations after discontinuation of selective serotonin reuptake
      inhibitors.

PMID- 7726329
TI  - Adverse effects of chewing methylphenidate.

PMID- 7726330
TI  - Efficacy of buspirone in the treatment of dementia with aggression.

PMID- 7726331
TI  - Secretion of amitriptyline and metabolites into breast milk.

PMID- 7726332
TI  - Priapism associated with bupropion treatment.

PMID- 7726333
TI  - When is an adolescent too thin?

PMID- 7726334
TI  - Creativity and mental illness.

PMID- 7726335
TI  - Creativity and mental illness.

PMID- 7726336
TI  - Creativity and mental illness.

PMID- 7726337
TI  - Brain and CSF volume differences in schizophrenic subtypes.

PMID- 7726338
TI  - Brain and CSF volume differences in schizophrenic subtypes.

PMID- 7726339
TI  - Acromioclavicular separation. Reconstruction using synthetic loop augmentation.
AB  - A total of 110 patients with a diagnosis of acromioclavicular joint separation
      were seen at our clinic between 1986 and 1991. Of these, 14 patients (12.7%) with
      grade III, IV, or V injuries required surgical reconstruction and were examined 2
      years after surgery. All 14 patients underwent acromioclavicular reconstruction
      using a synthetic loop passed through drill holes in the base of the coracoid and
      the anterior third of the clavicle. When the loop is tightened, the clavicle is
      reduced anatomically without the anterior subluxation caused by simple clavicular
      cerclage. At an average followup of 44.2 months, patients were evaluated using
      the University of California, Los Angeles, rating scale. Twelve of the 14 had
      good or excellent results and returned to normal sport and work activities at 6
      months. Of the two initial poor results, one required revision 1 month post
      operatively because the patient was noncompliant, and the other required
      manipulation under anesthesia 3 months after surgery. The results in these two
      patients at 2 years were good and excellent, respectively. We concluded that,
      when medically indicated, fixation of the clavicle to the coracoid using this
      technique yields satisfactory results in an athletic population.

PMID- 7726340
TI  - Partial tears of the anterior cruciate ligament. Are they clinically detectable?
AB  - Eight cadaveric lower extremities were examined by three experienced knee
      surgeons in blinded fashion. The knees were examined with intact anterior
      cruciate ligaments, sectioned anteromedial bundles, and completely sectioned
      anterior cruciate ligaments to evaluate detectable laxity changes. Lachman,
      anterior drawer, lateral pivot shift, and KT-1000 arthrometer testing were
      performed. Optimized biplanar radiography using a defined spatial coordinate
      reference system was performed with a 30-pound anterior force at 30 degrees of
      flexion to confirm clinical findings. Physical examination and arthrometer
      testing detected no difference between intact and partially sectioned anterior
      cruciate ligaments; these ligaments were significantly different than completely
      sectioned ligaments, with the Lachman test being the most sensitive. Despite
      consistent clinical detection of complete sectioning of the anterior cruciate
      ligament by both physical examination and arthrometer testing, neither method
      proved accurate in the diagnosis of isolated tears of the anteromedial bundle,
      but both did show that partially sectioned anterior cruciate ligament closely
      resembled intact ligament and differed significantly from completely sectioned
      ligament, as confirmed by radiologic data. Clinically diagnosed "partial tear" is
      likely to be complete rupture of the anterior cruciate ligament. Historically,
      clinically diagnosed partial tears of the anterior cruciate ligament have tended
      to "progress" to symptomatic instability. Our data imply these patients may have
      had functionally incompetent ligaments from time of injury and, in fact, were
      demonstrating the expected natural history of an anterior cruciate ligament
      deficient knee.

PMID- 7726341
TI  - An in vitro investigation into the effects of repetitive motion and nonsteroidal
      antiinflammatory medication on human tendon fibroblasts.
AB  - Soft tissue injuries due to repetitive motion are common sports injuries and are
      often treated with antiinflammatory therapies. We investigated the in vitro
      effects of repetitive motion and nonsteroidal antiinflammatory medication on
      human tendon fibroblasts. In addition, we studied the effects related to the
      presence of inflammatory cells. Repetitive motion was associated with an
      increased release of prostaglandin E2 and increased deoxyribonucleic acid (DNA)
      and protein synthesis. The presence of nonsteroidal antiinflammatory medication
      decreased prostaglandin E2 release and DNA synthesis but increased protein
      synthesis. Contact with macrophages caused a marked additional increase in
      prostaglandin E2 and a concomitant increase in DNA synthesis. Release of
      interleukin-6 by the macrophages also suggested that this cytokine plays a role
      in the response to repetitive motion. Our results can aid in the search for a
      more scientific approach to the treatment of soft tissue injuries associated with
      repetitive motion. They suggest that nonsteroidal antiinflammatory medication may
      have potentially negative effects during the proliferative phase of a healing
      since it was associated with decreased DNA synthesis. However, it may be
      beneficial in the maturation and remodeling phase since it stimulated protein
      synthesis.

PMID- 7726342
TI  - Meniscal repair. An experimental study in the goat.
AB  - To evaluate the healing potential of the meniscus, we created a longitudinal
      medial meniscal tear in both knees of 24 adult goats (48 knees). In all goats,
      the meniscus was repaired in one knee and left unrepaired in the other. The goats
      were placed into one of three groups based on the location of the tear and the
      status of the anterior cruciate ligament. At 6 months' followup, an arthrogram
      was obtained and the menisci were examined. In knees with an intact anterior
      cruciate ligament, tears in the peripheral 20% to 25% of the meniscus healed in
      six of seven repaired menisci, but in only one of seven of the unrepaired
      menisci. Tears in the peripheral 40% to 50% healed in only one of the eight
      repaired menisci and in none of the unrepaired menisci. When the anterior
      cruciate ligament was incised, tears in the peripheral 20% to 25% of the meniscus
      healed in only 1 of 8 repaired menisci and in none of the unrepaired menisci; the
      rest developed into complex tears. Arthrography was 92% accurate in predicting
      the status of meniscal repair. This study supports current clinical practices in
      meniscal repair and emphasizes the importance of tear location and knee stability
      in successful meniscal repair.

PMID- 7726343
TI  - The influence of muscle forces and external loads on cruciate ligament strain.
AB  - We know it is important to avoid excessive strain on reconstructed ligaments, but
      we do not know how individual muscles affect cruciate ligament strain. To answer
      this, we studied the effect of muscle forces and external loads on cruciate
      ligament strain. Nine cadaveric knee joints were tested in an apparatus that
      allowed unconstrained knee joint motion. Quadriceps, hamstring, and gastrocnemius
      muscle forces were simulated. Additionally, external loads were applied such as
      varus-internal or valgus-external rotation forces. Cruciate ligament strain was
      recorded at different knee flexion angles. Activation of the gastrocnemius muscle
      significantly (P < 0.05) strained the posterior cruciate ligament at flexion
      angles larger than 40 degrees. Quadriceps muscle activation significantly
      strained the anterior cruciate ligament when the knee was flexed 20 degrees to 60
      degrees (P < 0.01) and reduced the strain on the posterior cruciate ligament in
      the same flexion range (P < 0.05). Activation of the hamstring muscles strained
      the posterior cruciate ligament when the knee was flexed 70 degrees to 110
      degrees (P < 0.05). Combined varus and internal rotation forces significantly
      increased anterior cruciate ligament strain throughout the flexion range (P <
      0.05). The results suggest that to minimize strain on the ligament after
      posterior cruciate ligament surgery, strong gastrocnemius muscle contractions
      should be avoided beyond 30 degrees of knee flexion. The study also calls into
      question the use of vigorous quadriceps exercises in the range of 20 degrees to
      60 degrees of knee flexion after anterior cruciate ligament reconstruction.

PMID- 7726344
TI  - Efficacy of lateral retinacular release for painful bipartite patella.
AB  - We treated painful bipartite patella with a modified lateral retinacular release
      technique in 15 patients (16 knees). Bony union of the separated fragment and the
      patella was obtained in 15 of 16 knees within 8 months of surgery. Sustained
      traction acting on the patella laterally and proximally is presumed to cause the
      pain. The surgical technique to reduce this force proved effective not only in
      relieving the pain but also in achieving bony union. Painful bipartite patella
      can lead to excessive lateral pressure syndrome or patellar compression syndrome,
      these complications can be effectively treated by this surgical technique. In
      contrast to conventional treatments, such as excision of smaller fragments or
      osteosynthesis to achieve bony union, the modified lateral retinacular release
      technique is easy to perform and provides an effective means for relieving
      patellofemoral pain and achieving bony union.

PMID- 7726346
TI  - Surgical reconstruction of severe chronic posterolateral complex injuries of the
      knee using allograft tissues.
AB  - We report for the first time a reconstructive procedure of the posterolateral
      complex using allograft tissue to restore fibular collateral ligament function.
      The procedure is designed for knees where insufficient soft tissues are present
      and suitable autogenous graft tissues are not available. Twenty consecutive
      patients were studied; all returned for follow-up evaluation a mean of 42 months
      (range, 24 to 73) after surgery. The results were evaluated with the use of a
      comprehensive subjective and objective system that rated 20 factors. The success
      rate for the operative procedure was 76% (16 of 21 operations) as judged by knee
      stability examination and stress radiographs. Three of the reconstructions showed
      partial stretching and two failed. There was significant improvement from
      preoperative to follow-up scores of functional limitations in sports activities
      (P < 0.05), symptoms (P < 0.01), and overall scores (P < 0.0001). The immediate
      knee motion and rehabilitation program restored 0 degrees to 135 degrees of
      motion in all knees and was not deleterious to the reconstructions.

PMID- 7726345
TI  - Electromyographic analysis of the scapular muscles during a golf swing.
AB  - To describe the role of the scapular muscles in the golf swing, we studied 15
      competitive male golfers. Four muscles were studied bilaterally using dynamic
      electromyography and cinematography. In the trailing arm, the levator scapulae
      elevates while the rhomboid muscles retract the scapula during takeaway; both
      then stabilize the scapula through the remainder of the swing. In the leading
      arm, these muscles retract the scapula during forward swing and acceleration. The
      trapezius muscle in the trailing arm also demonstrates high activity during
      takeaway to aid in scapular retraction. In the leading arm, trapezius activity is
      high in forward swing and through the remainder of the swing to promote scapular
      retraction. The serratus anterior muscle activity is high in the trailing arm
      during forward swing and through the remainder of the swing to maximize scapular
      protraction. In the leading arm, the serratus anterior muscle has constant
      activity through all phases of the swing, which may explain the clinical scenario
      of muscle fatigue in high demand golfers. The golf swing and uncoiling action
      requires that the scapular muscles work in synchrony to maximize swing arc and
      clubhead speed. This study demonstrates the importance of the scapular muscles in
      the golf swing and the need for specific strengthening exercises.

PMID- 7726347
TI  - Anterior cruciate ligament strain behavior during rehabilitation exercises in
      vivo.
AB  - Before studying the biomechanical effects of rehabilitation exercises on the
      reconstructed knee, it is important to understand their effects on the normal
      anterior cruciate ligament. The objective of this investigation was to measure
      the strain behavior of this ligament during rehabilitation activities in vivo.
      Participants were patient volunteers with normal anterior cruciate ligaments
      instrumented with the Hall effect transducer. At 10 degrees and 20 degrees of
      flexion, ligament strain values for active extension of the knee with a weight of
      45 N applied to a subject's lower leg were significantly greater than active
      motion without the weight. Isometric quadriceps muscle contraction at 15 degrees
      and 30 degrees also produced a significant increase in ligament strain, while at
      60 degrees and 90 degrees of knee flexion there was no change in ligament strain
      relative to relaxed muscle condition. Simultaneous quadriceps and hamstrings
      muscles contraction at 15 degrees produced a significant increase in ligament
      strain compared with the relaxed state but did not strain the ligament at 30
      degrees, 60 degrees, and 90 degrees of flexion. Isometric contraction of
      hamstrings muscles did not produce change in ligament strain at any flexion
      angle. Exercises that produce low or unstrained ligament values, and would not
      endanger a properly implanted graft, are either dominated by the hamstrings
      muscle (isometric hamstring), involve quadriceps muscle activity with the knee
      flexed at 60 degrees or greater (isometric quadriceps, simultaneous quadriceps
      and hamstrings contraction), or involve active knee motion between 35 degrees and
      90 degrees of flexion.

PMID- 7726349
TI  - Revascularization of a human anterior cruciate ligament graft during the first
      two years of implantation.
AB  - The blood supplies of 45 unimpinged, human anterior cruciate ligament grafts were
      studied during the first 2 years of implantation. Grafts were defined as
      unimpinged by the low signal intensity of the graft observed on a sagittal proton
      density magnetic resonance scan. Magnetic resonance imaging with the intravenous
      contrast agent gadolinium diethylenetriamine pentacetic acid was used to evaluate
      the blood supply of the hamstring autograft as well as the periligamentous
      tissues by assessment of enhancement patterns after administration of the agent.
      The unimpinged anterior cruciate ligament graft acquired no discernible blood
      supply during the 2 years of implantation. The graft retained the same
      hypovascular appearance as the normal posterior cruciate ligament. In contrast,
      the periligamentous soft tissues were richly vascularized and covered the graft
      by 1 month. The viability of an unimpinged, human anterior cruciate ligament
      graft may depend more on synovial diffusion than on revascularization.

PMID- 7726348
TI  - Repairs by trephination and suturing of longitudinal injuries in the avascular
      area of the meniscus in goats.
AB  - Trephination may encourage healing of a tear in the avascular area of the
      meniscus, but healing may not be complete in unstable tears. We studied
      trephination with suture of longitudinal injuries in the avascular area of the
      medial meniscus in 20 goats; samples were studied at 3, 8, and 25 weeks. All 20
      tears treated by trephination and suture were completely (4 samples) or partly
      (16 samples) healed. The average tensile strength of the healed repair was 40.4
      kg/cm2 at 25 weeks. The level of DNA synthesis and tissue ingrowth decreased with
      time; DNA synthetic activity was also found in the chondrocytes of the menisci
      treated by suture alone. Only three of the menisci treated by suture alone were
      partly healed, and the remainder showed no gross evidence of healing. The
      addition of trephination to the sutured meniscus appears to promote healing of
      longitudinal injuries in the avascular area and is recommended rather than
      suturing or trephination alone. Meniscal suture alone may stabilize the tear and
      stimulate cell proliferation for healing, but it appears to be significantly
      restricted without an adequate blood supply.

PMID- 7726350
TI  - Local anesthesia for knee arthroscopy. Efficacy and cost benefits.
AB  - We performed a retrospective review of a series of knee arthroscopic procedures
      that were completed using local, general, or regional anesthesia to evaluate the
      efficacy of these anesthetic techniques. Operative time, complications or
      failures, procedures successfully performed, recovery room time and postoperative
      stay, and patient satisfaction were recorded. Local anesthesia with intravenous
      sedation compared favorably with the other techniques: operative time was not
      increased, a large variety of operative procedures were successfully completed,
      recovery time was significantly shortened, and patient satisfaction remained
      high. This technique offers several advantages over other types of anesthesia for
      knee arthroscopy, including improved cost effectiveness.

PMID- 7726351
TI  - Intraarticular lidocaine versus intravenous analgesic for reduction of acute
      anterior shoulder dislocations. A prospective randomized study.
AB  - We performed a prospective, randomized study to evaluate the use of injected
      lidocaine as an anesthetic for closed reduction of acute anterior shoulder
      dislocations. Thirty consecutive patients who presented at the emergency
      department with acute anterior shoulder dislocations were randomly placed in one
      of two groups. One group received an intraarticular injection of 20 ml of 1%
      lidocaine and the other group, intravenous injections of morphine sulfate and
      midazolam. The groups were compared regarding time of reduction maneuver,
      difficulty of reduction, subjective pain, complications, and total time spent in
      the emergency department. The lidocaine provided adequate anesthesia and
      secondary relief of muscle spasm in 15 of 15 (100%) patients. When compared with
      the intravenous sedation group, the lidocaine group showed no statistically
      significant difference in time for reduction maneuver, difficulty of reduction,
      or subjective pain. The lidocaine group had no complications and had a
      statistically significant shorter emergency department visit when compared with
      the intravenous sedation group (mean, 78 minutes versus 186 minutes; P = 0.004).
      Lidocaine provides excellent anesthesia for patients with uncomplicated anterior
      shoulder dislocations and can be very beneficial when sedation is
      contraindicated. Lidocaine injections also proved to be cost effective in our
      institution, reducing total costs by as much as 62%.

PMID- 7726353
TI  - A threshold and continuum of injury during active stretch of rabbit skeletal
      muscle.
AB  - Previous studies of acute muscle injury with active stretch used cyclic
      stretching or stretching the muscle to complete muscle-tendon dissociation. This
      study tried to determine minimal force required for skeletal muscle injury with
      one active stretch to establish an injury "threshold." Tibialis anterior and
      extensor digitorum longus rabbit muscles were actively stretched at 10 cm/sec to
      60%, 70%, 80%, or 90% of the force required to passively fail tibialis anterior
      and extensor digitorum longus muscles of the control (contralateral) limb.
      Maximal isometric contractile force, tensile properties, histology, and
      electromyography were measures of injury. Both muscles of the 60% group showed no
      abnormalities in maximal isometric contractile force, tensile properties,
      histology, or electromyographic activity; 70%, 80%, and 90% groups showed
      diminished maximal isometric contractile force, muscle fiber disruption, edema,
      hemorrhage, and decreased electromyographic maximal voltage amplitude. The 90%
      group also showed alterations in tensile properties at failure along with
      connective tissue damage. Injury site included fiber disruption both at the
      distal myotendinous junction and muscle belly, with injury noted initially at the
      distal myotendinous junction in the 70% group. Electromyographic studies showed
      maximal isometric contractile force and maximal voltage correlated well as
      indices of damage. This study shows that a threshold and continuum for active
      stretch-induced injury exist, with muscle fiber disruption occurring initially
      and connective tissue disruption occurring only with larger muscle displacements.

PMID- 7726352
TI  - The effect of intraarticular injection of morphine and bupivacaine on
      postarthroscopic pain control.
AB  - This study sought to compare the effects of morphine, bupivacaine, and saline
      injected into the knee after arthroscopic surgery. In a double-blind, randomized
      trial, 124 patients received either bupivacaine, morphine, bupivacaine and
      morphine, or saline at the completion of surgery. Postoperative pain was assessed
      with a 100-mm visual analog pain scale. Analgesic requirements were calculated,
      and weightbearing status was recorded. We found that morphine alone injected
      intraarticularly at the completion of arthroscopic knee surgery had no
      significant effect on postoperative pain, need for supplemental analgesia, or
      weightbearing status. Patients receiving morphine in combination with bupivacaine
      did not demonstrate any statistically significant improvement over those
      receiving bupivacaine alone. Therefore, our results failed to show any beneficial
      effect of morphine used for postoperative analgesia, either alone or in
      combination with bupivacaine. The overall pattern in all patients demonstrated
      decreased pain scores, decreased analgesic use, and increased weightbearing
      status as the observation period progressed. Finally, preoperative pain was
      correlated with pain at discharge, indicating that the most significant predictor
      of postoperative pain was preoperative level of discomfort.

PMID- 7726354
TI  - Comparison of various icing times in decreasing bone metabolism and blood flow in
      the knee.
AB  - In a previous study we used technetium-99m bone scans to show that cooling a knee
      for 20 minutes with a standard ice wrap will decrease soft tissue blood flow by a
      mean of 26%, and skeletal blood flow and metabolism by 19%. The present study
      examined the effects of shorter and longer icing periods to determine minimum
      cooling time for a measurable and consistent decrease, and time to produce
      maximal decrease within a safe period of icing (< 30 minutes). Thirty-eight
      subjects were studied. An ice wrap was applied to one knee for an assigned time
      (5, 10, 15, 20, or 25 minutes). Triple-phase bone scans of knees were obtained;
      mean percentages of decrease in the iced knee for each of the five time groups at
      each of the three phases of the bone scan were calculated and compared. Mean
      decreases of 11.1% in soft tissue blood flow, and 5.1% in skeletal metabolism and
      blood flow were measured at 5 minutes; maximums of 29.5% and 20.9%, respectively,
      were obtained at 25 minutes. A small but consistent decrease in soft tissue blood
      flow and skeletal blood flow and metabolism in a knee appear to be obtained with
      as little as 5 minutes of ice application. This effect is time-dependent and can
      be enhanced three- to four-fold by increasing the ice application time to 25
      minutes.

PMID- 7726355
TI  - Observations on the injury mechanism of anterior cruciate ligament tears in
      skiers.
AB  - The purpose of this study was to demonstrate the uniqueness of the injury
      mechanism for acute complete tears of the anterior cruciate ligament in
      recreational alpine skiers by using patterns of osseous injury as detected by
      magnetic resonance imaging. We treated 42 patients (average age, 32 years) who
      met the following criteria: 1) acute complete anterior cruciate ligament tear
      incurred during skiing, 2) no history of knee injury, 3) magnetic resonance
      imaging within 30 days of injury, and 4) arthroscopy and anterior cruciate
      ligament reconstruction or both for documentation of all intraarticular injury.
      An osseous injury detected by magnetic resonance imaging was seen in the lateral
      femoral condyle in 17 (40%) of the patients and was located over the terminal
      sulcus in 15 of these patients; only 1 had arthroscopic evidence of chondral
      injury. Four (10%) of the 42 patients had a bone bruise on the medial femoral
      condyle; all were located at the extreme posterior margin. Thirty-four patients
      (81%) had a bone bruise on the lateral tibial plateau; 33 were located at the
      extreme posterior margin and 27 of these were at the posterolateral tibial rim.
      Twelve patients (29%) had a bone bruise on the medial tibial plateau; all were
      located on the posterior margin.

PMID- 7726356
TI  - Semitendinosus augmentation of acute patellar tendon repair with immediate
      mobilization.
AB  - We report four cases of acute midsubstance rupture of the patellar tendon that
      were treated with primary surgical repair along with semitendinosus autograft
      augmentation. The goal of this treatment was to allow immediate mobilization of
      the knee with a single operative procedure. We also demonstrate a technique for
      determining patellar position intraoperatively. Patients were tested for
      functional performance at an average final followup of 40 months (range, 20 to
      66) including hamstring and quadriceps muscle strength evaluation, completion of
      a functional questionnaire, functional test performance, range of motion
      assessment, and patellar tendon length measurement. In evaluating the results,
      all cases were essentially identical to the nonoperated side, except one knee
      that had multiple associated ligament injuries. The multitude of injuries to this
      knee are likely the cause of the discrepancy. Immediate midsubstance patellar
      tendon repair with semitendinosus augmentation allowed immediate mobilization,
      which decreased the recovery period and improved the outcome of rehabilitation.
      Furthermore, a second surgery for hardware removal was not needed. These two
      factors--early and improved rehabilitation and the decreased chance of a second
      surgery--affect the cost of treatment of this injury. All isolated patellar
      tendon injuries in the study had excellent function at followup. For these
      reasons, we recommend this procedure for acute patellar tendon ruptures.

PMID- 7726357
TI  - Prevention of arthrofibrosis after anterior cruciate ligament reconstruction
      using the central third patellar tendon autograft.
AB  - A retrospective analysis was performed to explain the decreasing incidence of
      postoperative arthrofibrosis of the knee in 191 consecutive patients who had
      anterior cruciate ligament reconstruction using the central third patellar tendon
      from 1987 through 1991. Follow-up data were available on 188 patients (98%). Age,
      sex, time interval from injury, preoperative motion, and concomitant meniscal
      repair or partial meniscectomy were evaluated for their significance as risk
      factors. Twenty-two of 188 patients (12%) developed arthrofibrosis; the incidence
      was lower when the acute anterior cruciate ligament reconstruction was delayed at
      least 3 weeks from the injury, and when preoperative extension was 10 degrees or
      better. Age, sex, preoperative flexion, and need for concomitant meniscal surgery
      were not risk factors. The postoperative motion protocol evolved during the study
      period. Group 1 patients were braced in 45 degrees of flexion for 1 week before
      passive extension was allowed. In Group 2, motion was started after 48 hours.
      Group 3 patients were braced in full extension, with motion starting with 24
      hours. With these changes, the incidence dropped from 23% to 3%. Decreases in the
      incidence of arthrofibrosis with modifications in operative technique and
      postoperative analgesia were not statistically significant.

PMID- 7726358
TI  - Superior labrum-biceps tendon complex lesions of the shoulder.
AB  - The detachment of the superior labrum from anterior to posterior has previously
      been reported. This lesion has been classified into four types. It was our
      impression that not all superior labrum abnormalities fit into such a
      classification system and that the mechanism of injury was distinctly different.
      During a 5-year period, 84 of 712 (11.8%) patients had significant labral
      abnormalities; 52 of 84 patients (6.2%) had lesions that fit within the
      classification system (Type II, 55%; III 4%; IV, 4%), but 32 of 84 patients (38%)
      had significant findings that could not be classified. These unclassifiable
      lesions fit into three distinct categories. Two of three patients described a
      traction injury to the shoulder. Only 8% sustained a fall on an outstretched arm;
      75% had a preoperative diagnosis of impingement based on consistent history and
      provocative testing; however, when examined under anesthesia, 43% of the
      shoulders were considered to have increased humeral head translation when
      compared with the other shoulder. Recognition of superior labrum-biceps tendon
      detachment should prompt the surgeon to investigate glenohumeral instability as
      the source of a patient's complaints.

PMID- 7726359
TI  - Comparison of open and arthroscopically assisted rotator cuff repairs.
AB  - Open rotator cuff repair has shown reliable results in terms of pain relief and
      improved shoulder function. Recently, however, arthroscopically assisted rotator
      cuff repair has shown promising preliminary results. We compared the results of
      these two procedures with regard to pain, function, range of motion, strength,
      patient satisfaction, and return to previous activity. Thirty-seven rotator cuff
      repairs were evaluated in 36 patients with a minimum followup of 2 years. The
      open repair group comprised 20 shoulders with an average followup of 3.3 years;
      the arthroscopically assisted repair group comprised 17 shoulders with an average
      followup of 3.2 years. Overall, the open repair group had 80% good-to-excellent
      results and 88% patient satisfaction, and the arthroscopically assisted repair
      group had 85% good-to-excellent results and 92% patient satisfaction. Shoulder
      flexion and abduction strength, the size of the tear repaired, and the functional
      outcome did not differ significantly between the two groups. In general, however,
      small and moderate-sized tears (< 3 cm) had better functional outcome with
      arthroscopically assisted repair. The arthroscopically assisted repair group was
      hospitalized 1.2 days less and returned to previous activity an average of 1
      month earlier. In the surgical treatment of symptomatic complete rotator cuff
      tears, arthroscopically assisted rotator cuff repair is as effective as open
      repair.

PMID- 7726360
TI  - Clear cell meningioma. A clinicopathologic study of a potentially aggressive
      variant of meningioma.
AB  - Since clear cell meningioma has only recently been recognized as a morphologic
      entity, its pathobiology has not been studied. Fourteen examples occurring in
      seven females and six males, ages 9 to 82 years (mean 29 years), were examined;
      one was associated with type 2 neurofibromatosis. Of these cases, seven (50%)
      were spinal-intradural (six lumbar, one thoracic), three (21%) arose in the
      posterior fossa (cerebellopontine angle), three (21%) were supratentorial, and
      one (7%) was centered upon the foramen magnum. In one case (8%), two tumors were
      considered to be independent primaries. One tumor (8%) appeared to show no dural
      attachment. Thirteen tumors were subject to complete study. All were composed of
      sheets of clear, glycogen-rich, polygonal cells forming only a few vague whorls.
      Hyalinization, both stromal and perivascular, was often extensive. Mitoses were
      rare in primary tumors. Immunohistochemistry showed vimentin and epithelial
      membrane antigen staining to be reactive in 100%. Stains for S-100 protein and
      CAM 5.2 were negative. Progesterone and estrogen receptor staining was observed
      in 77% and 0%, respectively. Ultrastructural study showed abundant cytoplasmic
      glycogen, a few cytoplasmic lumina, intermediate filaments, interdigitation of
      cell membranes, and desmosomal junctions. The means, medians, and ranges of
      proliferating cell nuclear antigen (PCNA) and MIB-1 antigen labeling indices for
      nonrecurring and recurring tumors were 10.4%, 8.8%, 0.8-23.4% and 11%, 1.4%, 0.1
      50.3%, as compared with 7.4%, 6.7%, 2.9-17.2% and 13.3%, 13.4%, 3.3-25.7%,
      respectively. Twelve successful DNA ploidy studies showed that 11 tumors (85%)
      were diploid and one was tetraploid; percentage S-phase determinations varied
      from 4 to 9% (mean 6.0%). Recurrence was noted in eight patients (61%) (five of
      whom had multiple recurrences); there was local discontinuous spread in two cases
      (15%) and widespread cranial to spinal metastasis in one case (8%). Three
      patients (23%) are dead of disease. In summary, clear cell meningiomas are
      morphologically unique, show no sex predilection, affect primarily the lumbar
      region and cerebellopontine angle, and despite their benign appearance, may be
      inordinately aggressive, particularly intracranial examples. No close association
      was noted between recurrence or clinical outcome and such factors as mitotic
      activity, PCNA proliferation indices, percent S-phase determination, or DNA
      ploidy status. In contrast, MIB-1 proliferation indices were appreciably higher
      among recurring tumors.

PMID- 7726361
TI  - Ectomesenchymal chondromyxoid tumor of the anterior tongue. Nineteen cases of a
      new clinicopathologic entity.
AB  - We present 19 cases of a previously undescribed myxoid tumor of the anterior
      tongue. These lesions occurred in nine women and 10 men aged 9 to 78 years
      (median, 32 years). Most tumors were seen as slow growing, painless nodules in
      the anterior dorsal tongue. The duration of growth ranged from a few months to 10
      years. All tumors were treated by surgical excision, and two recurred.
      Microscopically, they exhibited a lobular proliferation of ovoid and fusiform
      cells, which often had multilobated nuclei and occasional foci of atypia, in a
      chondromyxoid background. Some tumors entrapped muscle or nerve fibers and had a
      tendency for blunt infiltration of adjacent tissue. The cells were diffusely and
      intensely immunoreactive for glial fibrillary acidic protein (GFAP) and
      cytokeratin but were decorated less frequently with antibodies for smooth muscle
      actin and S-100 protein. Reactivity for epithelial membrane antigen and desmin
      was not found. We believe these tumors fail to meet established clinicopathologic
      criteria for any existing myxoid neoplasms of the tongue, including nerve sheath
      myxoma, myoepithelioma, benign mixed tumor, ossifying fibromyxoid tumor of soft
      parts, extraskeletal myxoid chondrosarcoma, and glial and chondroid choristomas
      or heterotopias. Although the histogenesis of this neoplasm is unclear, we
      suspect that a cell of undifferentiated ectomesenchyme is the progenitor and
      suggest the descriptive term ectomesenchymal chondromyxoid tumor (ECT) of the
      anterior tongue be adopted.

PMID- 7726362
TI  - B-cell monoclonality, Epstein Barr virus, and t(14;18) in myoepithelial
      sialadenitis and low-grade B-cell MALT lymphoma of the parotid gland.
AB  - Low-grade mucosa-associated lymphoid tissue (MALT) type B-cell lymphomas of the
      salivary gland arise in a background of myoepithelial sialadenitis (MESA),
      usually in association with Sjogren's syndrome. The distinction between benign
      MESA and early lymphoma has proved difficult using histological criteria alone
      and the significance of B-cell monoclonality in this respect is controversial. We
      have used immunohistochemistry and polymerase chain reaction (PCR) amplification
      of immunoglobulin heavy-chain VDJ regions to assess clonality in biopsies from 45
      patients with lymphoid infiltration of the parotid. Sequential biopsies spanning
      3-18 years were available from seven patients, three of whom had developed
      disseminated nodal B-cell lymphoma. In light of previous studies, each biopsy was
      additionally analyzed for the presence of t(14;18) and Epstein Barr Virus (EBV)
      DNA using PCR. Monoclonality was detected in 34/45 cases. Comparison of histology
      with clonality confirmed earlier suggestions that the emergence of an
      identifiable population of centrocyte-like B cells around ducts or epithelial
      islands correlated with monoclonality. In six of seven patients with sequential
      biopsies PCR fragments of identical size were amplified from each biopsy,
      suggesting that demonstrable monoclonality in "lymphoepithelial"
      lymphoproliferative lesions of the salivary gland is indicative of lymphoma. No
      t(14;18) chromosome translocations were identified; EBV sequences were detected
      in three of 45 cases.

PMID- 7726363
TI  - Adenocarcinomatous transformation of intracranial germ cell tumors.
AB  - Germ cell tumors arising in the gonads, retroperitoneum, and mediastinum are
      occasionally overgrown by cancers of somatic type that are widely assumed to
      derive from the "malignant transformation" of included teratomatous tissues.
      These malignant, nongerminal neoplasms are typically chemoresistant, and their
      emergence is often associated with fatal treatment failure. Only rare, well
      documented reports of sarcomatous transformation complicating intracranial germ
      cell neoplasia are on record. We describe two nongerminomatous germ cell tumors
      of the pineal region that underwent transformation into enteric-type
      adenocarcinoma. Both recurred in a locally aggressive fashion, one proving
      rapidly fatal owing to the development of multiple cerebral and cerebellar
      metastases and spinal leptomeningeal adenocarcinomatosis.

PMID- 7726365
TI  - Myoblastomatoid (histiocytoid) carcinoma of the breast. A type of apocrine
      carcinoma.
AB  - Thirteen carcinomas of the breast having in common neoplastic cells with granular
      to foamy cytoplasm are described. These cells exhibit apocrine differentiation as
      demonstrated by immunocytochemical and in situ hybridization studies. These
      tumors can be easily misinterpreted as either fibrohistiocytic or myoblastomatoid
      (granular cell) tumors. Therefore, the designation of myoblastomatoid
      (histiocytoid) invasive carcinomas seems the most appropriate for this specific
      group of apocrine carcinomas.

PMID- 7726364
TI  - Solitary lung lesions in Wegener's granulomatosis. Pathologic findings and
      clinical significance in 25 cases.
AB  - We describe 25 cases of Wegener's granulomatosis presenting with solitary lung
      lesions to compare the clinical and pathologic findings in these cases with those
      of the more common multifocal disease and also to evaluate the clinical
      significance of solitary lung lesions occurring in the absence of extrapulmonary
      disease. The clinical findings in our patients with solitary Wegener's were
      similar to those in generalized disease. Men were affected slightly more often
      than women, and the average age of onset was 53 years. Likewise, no major
      pathologic differences were found between solitary and multifocal disease.
      Classic necrotizing granulomatous inflammation and necrotizing vasculitis were
      the most common findings, although other variants were occasionally encountered,
      including the eosinophilic variant (two cases), the bronchocentric variant (one
      case), and small-vessel vasculitis and capillaritis (one case). Three cases had
      prominent areas of bronchiolitis obliterans-organizing pneumonia. Progressive
      disease occurred in all seven patients who manifested solitary lung lesions
      without extrapulmonary involvement and were not treated because the diagnosis was
      initially unrecognized. Pathologists need to be alert to the possibility of
      Wegener's granulomatosis causing solitary lung lesions because treatment should
      be promptly instituted.

PMID- 7726366
TI  - Placental transmogrification of the lung, a histologic variant of giant bullous
      emphysema. Clinicopathological study of three further cases.
AB  - Placental transmogrification of the lung was described by Chesney in 1978 as an
      unusual cystic lesion involving a single pulmonary lobe (3). We studied three
      additional cases with identical clinical and pathologic features. The patients
      were a 33-year-old woman and men aged 24 and 27 years. Each patient was first
      seen with respiratory distress; one had repeated pneumothoraces.
      Radiographically, an enlarging cystic lesion was present in a lower (two) or
      middle (one) lobe. The lesion had been present for 10 years in one patient. In
      two patients, mediastinal shift was noted. Lobectomy was curative in all
      instances. Grossly there was a uni- or paucilocular cyst lined by papillary
      structures. Microscopically, the papillae contained proliferating blood vessels,
      lymphoid nodules, smooth muscle, and fat. Sclerotic foci obliterated the vessels
      in some areas. The growth pattern and topography resembled those of placental
      villi. Systematic review of the histologic features in other lungs with marked
      emphysema revealed a spectrum of similar changes and suggested that the lesion in
      our patients may be a complication of bulla formation and is most likely the
      clinico-pathologic analog of the "vanishing lung" syndrome (idiopathic giant
      bullous emphysema).

PMID- 7726368
TI  - Intraductal papillary mucinous neoplasms of the pancreas associated with so
      called "mucinous ductal ectasia". Histochemical and immunohistochemical analysis
      of 29 cases.
AB  - Twenty-nine patients (20 men, nine women; mean age, 65.9 years; range, 49-77
      years) with intraductal papillary mucinous neoplasms associated with so-called
      "mucinous ductal ectasia" of the pancreas were studied both histochemically and
      immunohistochemically. These cases included six cases of hyperplasia, 13
      adenomas, and 10 adenocarcinomas. The mean sizes of the hyperplasia, adenomas,
      and adenocarcinomas were 2.0 cm, 3.0 cm, and 4.8 cm in diameter, respectively.
      Tumor size correlated with the degree of cellular atypia. The proliferative rates
      were significantly higher in the carcinomatous epithelium with those in the
      hyperplastic and adenomatous epithelia. The polarity of distribution of
      carcinoembryonic antigen and carbohydrate antigen 19-9 were better preserved in
      the hyperplastic epithelia than in the carcinomatous epithelia. On the other
      hand, the papillary and nonpapillary hyperplastic epithelium contained mainly a
      neutral periodate-reactive glycoprotein with only trace amounts of sialomucins
      and sulphomucins. In addition, the adenomatous epithelium contained mostly
      sialomucins with a small amount of sulphomucins. The carcinomatous epithelium
      contained predominantly sulphomucin. The results of both the histological and
      immunohistochemical studies suggested the possibility of a sequential change from
      nonpapillary and papillary hyperplasia, via adenoma, to carcinoma in intraductal
      papillary-mucinous neoplasms associated with mucinous ductal ectasia. Moreover,
      these results, in combination with the histochemical findings, are considered
      helpful in making an appropriate preoperative diagnosis with endoscopic
      pancreatic ductal biopsy specimens, thus enabling the surgeon to select the most
      appropriate surgical procedure.

PMID- 7726367
TI  - Primary low-grade hepatic B-cell lymphoma of mucosa-associated lymphoid tissue
      (MALT)-type.
AB  - We describe the clinical, histological, and immunohistochemical features of four
      cases of primary low-grade B-cell lymphoma of the liver. The lymphomas were first
      seen as a solitary nodule in two patients and as two nodules in the third
      patient. These were found incidentally in an otherwise normal liver during
      abdominal surgery for other causes. In the fourth patient, several up to 2 cm
      nodules of lymphoma were found in a liver removed before transplant for chronic
      active hepatitis and cirrhosis. There was no evidence of lymphoma elsewhere in
      any of the patients. One patient has remained well, without evidence of lymphoma,
      1 year after resection, one died intraoperatively, one is lost to follow-up, and
      the transplanted patient died 1 year after transplant from complications without
      evidence of recurrent lymphoma. The histology was typical of low-grade B-cell
      lymphoma of mucosa-associated lymphoid tissue (MALT)-type with centrocyte-like
      cells surrounding reactive B-cell follicles and forming lymphoepithelial lesions
      with bile ducts. Primary hepatic lymphomas are rare, and most reported cases have
      been high-grade B-cell lesions. The liver should be added to the list of
      extranodal sites where low-grade MALT lymphoma may occur.

PMID- 7726369
TI  - Interleukin-6 and interleukin-1 beta production in a pediatric plasma cell
      granuloma of the lung.
AB  - Plasma cell granuloma (PCG) is a pseudotumor of unknown origin. It is frequently
      accompanied by acute-phase clinical and biological signs that resume after
      complete surgical removal, suggesting production of soluble mediators. We
      therefore investigated the role of cytokines in a previously healthy 10-year-old
      boy with a PCG of the lung and systemic symptoms. In this case, very high serum
      levels of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) were found
      before tumor excision, associated with inflammatory signs including major hyper
      gamma-globulinemia. Pathologic analysis of the tumor showed an accumulation of
      fibroblasts and plasma cells producing immunoglobulins. Local production of IL-1
      beta and IL-6 could be demonstrated at the messenger RNA (mRNA) level by the
      reverse transcriptase polymerase chain reaction and could be attributed to
      inflammatory cells by in situ hybridization and immunohistochemistry, whereas
      plasma cells exhibited membrane expression of the IL-6 receptor. Postsurgery
      follow-up showed rapid normalization of serum IL-1 beta and IL-6, whereas
      inflammatory protein levels decreased. This confirms the local production of
      cytokine within the PCG and raises the question of whether a dysregulation of
      cytokine production initiates the disease.

PMID- 7726371
TI  - Variants of liposarcoma.

PMID- 7726370
TI  - An unusual round cell tumor of the tibia with granular cells.
AB  - We present the clinical, radiographic and histopathologic findings of an unusual
      tumor that originated in the diaphysis of the tibia in a 10-year-old boy.
      Clinical symptoms had been present for approximately 2 years and radiographic
      abnormalities for > or = 8 months before biopsy and subsequent resection of the
      neoplasm. The child is doing well 4 1/2 years later. Microscopically, the tumor
      was not typical of any bone tumor with which we are familiar. It was a round-cell
      tumor with extensive fibrosis, prominent cytoplasmic granularity, and isolated
      immunoreactivity for vimentin, epithelial membrane antigen, and antichymotrypsin.
      Ultrastructural examination uncovered the presence of both well-formed desmosomes
      and cell-associated basement membrane material in addition to abundant
      phagolysosomes. Classification of this tumor is a challenge; the differential
      diagnosis includes atypical adamantinoma, atypical Ewing's sarcoma, and small
      cell osteosarcoma. We favor the former interpretation, although we raise the
      possibility that it may be a unique lesion.

PMID- 7726372
TI  - Variants of liposarcoma.

PMID- 7726373
TI  - Nerve sheath tumors.

PMID- 7726374
TI  - Experience of King Faisal Specialist Hospital and Research Center with Saudi
      organic acid disorders.
AB  - The Inborn Errors of Metabolism and Neurology Services of the King Faisal
      Specialist Hospital and Research Centre (KFSH&RC) and Armed Forces Hospital have
      received more than 1,500 patients suspected of having an organic acid disorder
      (OAD) during a period of four years. Of these, 307 patients suspected of having
      an organic acid disorder (OAD) during a period of four years. Of these, 307
      patients, approximately 20%, had a clearly identifiable disorder. Identified
      OAD's constituted one-quarter of all patients diagnosed as having various types
      of inborn errors of metabolism during this period, in these clinical services.
      Prolonged follow-up was available in the majority of cases, allowing detailed
      clinical, neuroradiologic and neurophysiologic descriptions. Fifty patients (16%)
      had rare disorders by standards in the West. Approximately 25% were 'neurologic
      organic acidurias.' This is a new term we are introducing for OAD's manifesting
      primarily with neurologic signs, but without appreciable acidosis, hypoglycemia
      or hyperammonemia. In this special issue, we present the KFSH&RC experience with
      the rare disorders as individual articles. We estimate the frequency of OAD's in
      Saudi Arabia as 1/740 births. The increased frequency of OAD's in Saudi Arabia is
      probably due to increased consanguinity, since most OAD's occurred in excess in
      certain tribes; and due to increased surveillance and testing by our group. Saudi
      Arabia provides a unique opportunity for research in this area of pediatrics.

PMID- 7726375
TI  - CT and MR of the brain in the diagnosis of organic acidemias. Experiences from
      107 patients.
AB  - The results of CT and/or MRI of the brain in 107 patients with different types of
      organic acidemia are presented. The CSF spaces were wide in more than two-thirds
      of the patients, in 46 slightly-to-moderately and in 26 markedly-to-severely
      dilated. Marked widening of the operculae was found in all 5 patients with
      glutaric acidemia type 1, but open opercula was also found in other organic
      acidemias. White matter changes were found in about half the patients, in 28
      mildly-to-moderately pronounced, in another 28 marked or severe. Basal ganglia or
      central pathway pathology was seen in a total of 34 patients, i.e. 32%. These
      changes in 25 patients involved the caudate and/or lentiform nuclei: in 14 cases
      the T2 signal was increased and volume loss was present, in 9 cases increased T2
      signal with preserved volume was found (in one of these the changes were
      transient). In 2 patients, both with ethylmalonic aciduria (cause unknown), only
      small high T2 spots were seen in the caudate heads and the putamina. In 4
      patients, all suffering from methylmalonic acidemia, only the globus pallidus was
      affected. In 3 patients, all with beta-ketothiolase deficiency, high T2 intensity
      changes were seen only in the postero-lateral putamina. The remaining 8 patients
      represent a variety of different locations of lesions. The CT or MRI findings in
      many patients with organic acidemias should alert the radiologist that a
      neurometabolic disorder may be present; in some cases the location and appearance
      of the lesions may even suggest the correct diagnosis.

PMID- 7726376
TI  - Ethylmalonic aciduria: an organic acidemia with CNS involvement and vasculopathy.
AB  - Five infants from 3 families, one Egyptian, two Yemeni, are described with a
      progressive encephalopathy, four of whom have been studied in detail. All
      patients showed vascular lesions of the skin, characterized by waxing and waning
      petechiae and ecchymoses. Acrocyanosis was present in three patients. All
      patients showed retinal lesions characterized by tortuous veins. Protracted
      diarrhea was not a consistent finding, although they had metabolic crisis in
      association with diarrhea. They did not show failure to thrive. The neurologic
      symptoms were indicative of a progressive pyramidal tract disease. Three patients
      died following sudden emergence of severe basal ganglia, putaminal and head of
      caudate lesions. In one patient the CT changes in brain were suggestive of
      infarction. The patients who died manifested pulmonary congestion, or wet lung,
      and respiratory difficulties during the terminal stage of the disease. In all
      patients before and during the terminal event, mild-to-moderate hematuria, and in
      two RBC in CSF, was observed. In one patient there was mild hemoperitoneum at the
      terminal event. The urine organic acids indicated increased excretion of
      ethylmalonic, methylsuccinic, glutaric, and adipic acids. The patients invariably
      showed lactic acidosis, but no ketosis, during and in between the acidotic
      attacks of the disease. The acylcarnitine profile in blood of two patients showed
      a pronounced increase in C4 and C5 carnitine esters. In three patients, biopsies
      from petechiae indicated absence of an immune event, showing only fresh
      hemorrhage. An immunologic study in one patient was normal for the
      suppressor:cytotoxic lymphocyte ratio and concentration of interleukin-2 receptor
      during and in between hemorrhagic attacks. The cytochrome c oxidase activity in
      fibroblasts was normal. The rate of oxidation of glucose, leucine, isoleucine,
      valine, propionate and butyrate by fibroblasts was normal. The disease is not
      responsive to treatment with riboflavin, ascorbic acid, vitamin E, glycine, or
      carnitine. One patient remained stable on prolonged large doses of
      methylprednisolone. The biochemical defect leading to ethylmalonic aciduria in
      this disease remains unknown.

PMID- 7726377
TI  - Neurophysiologic correlates of organic acidemias: a survey of 107 patients.
AB  - The files of 107 patients with 19 different types of organic acidemia were
      reviewed retrospectively. Approximately 50% of the patients had abnormal
      electroencephalogram (EEG) at the time of initial study. In patients who had
      serial studies, the EEG deteriorated in 38% and improved in 15%. The predominant
      EEG abnormality encountered was slowing of the background activity in various
      degrees. Focal or generalized paroxysmal activity occurring in conjunction with
      slow background activity indicated a poor prognosis. Brainstem auditory evoked
      potentials (BAEP), visual evoked potentials (VEP), and somatosensory evoked
      potentials (SEP) were analyzed. The VEP was abnormal in 44%, BAEP in 39%, and SEP
      in 29% of the patients. Given the magnitude and frequency by which
      neurophysiological abnormalities occur in organic acidemias, neurophysiology
      testing provides complementary functional information and has an important place
      in the clinical work-up of these diseases.

PMID- 7726378
TI  - 3-Methylglutaconic aciduria: ten new cases with a possible new phenotype.
AB  - 3-Methylglutaconic aciduria is an organic aciduria with diverse phenotypic
      presentations. In more than half of the cases it is a 'neurologic or silent
      organic aciduria', and, except for one subtype, the biochemical defect is
      unknown. This report describes 10 new patients. Four of them presented with early
      global neurologic involvement and arrested development. They rapidly became
      demented, developed myoclonus or tonic-clonic seizures, spastic quadriplegia,
      deafness and blindness, and died. Three had acidosis and hypoglycemia neonatally;
      later, myoclonus and deafness, and eventually severe mental retardation and
      spastic quadriplegia developed. One patient died. In three children who presented
      with sudden onset of extrapyramidal tract symptoms, with or without optic
      atrophy, the clinical presentation was significantly different from that
      described either for 'unspecified' type or for Costeff syndrome. All three
      patients showed clinical improvement soon after treatment with coenzyme Q.

PMID- 7726379
TI  - A new patient with alpha-ketoglutaric aciduria and progressive extrapyramidal
      tract disease.
AB  - A 4.5-year-old boy with chronic progressive encephalopathy is described. The
      clinical presentation initially included seizures and hypotonia which later
      evolved into severe extrapyramidal disease and dementia. The gas
      chromatography/mass spectrometry (GC/MS) analysis of urine indicated that alpha
      ketoglutarate was increased 210 times and aconitic acid 80 times. No disturbance
      of acid/base balance, lactic acid or ammonia metabolism accompanied this clinical
      picture. The fibroblasts contained 29% of normal alpha-ketoglutarate
      dehydrogenase activity, while the activity of another mitochondrial marker
      enzyme, glutamate dehydrogenase, was normal. The neuroimaging studies revealed
      bilateral striatal necrosis. The clinical and biochemical findings were almost
      identical to two previously reported patients. Experience with this patient
      emphasizes the need for detailed organic acid biochemical investigation in any
      progressive encephalopathy and that extrapyramidal tract signs should evoke the
      possibility of alpha-ketoglutaric aciduria, among other 'neurologic organic
      acidemias'.

PMID- 7726380
TI  - 3-Ketothiolase deficiency: a review and four new patients with neurologic
      symptoms.
AB  - 3-Ketothiolase deficiency (3KTD) manifests with intermittent acidosis and is due
      to deficiency of mitochondrial 2-methylacetoacetate thiolase. Only 22 patients
      have been previously reported. Although its variable clinical presentation is
      recognized, the associated neurological findings have not been detailed. We
      report four new patients all with significant neurological symptoms. Three
      patients were examined with MRI of the brain which showed increased T2 intensity
      within the posterior lateral part of the putamen bilaterally. In two the MRI was
      otherwise normal; in one delayed myelination was also seen. These MRI putaminal
      findings may be typical enough to suggest the diagnosis of 3KTD. Two of the three
      had abnormal EEGs; one had an abnormal VEP. 3KTD can thus occur as an organic
      acidemia associated with encephalopathy.

PMID- 7726381
TI  - Unusual presentations of propionic acidemia.
AB  - The files of 25 patients with propionic acidemia (PA), followed by the Inborn
      Errors of Metabolism Service (IEMS) at King Faisal Specialist Hospital and
      Research Centre (KFSH & RC) from 1990 to 1993, were studied retrospectively. In
      14 patients PA presented acutely with acidosis, hyperammonemia and
      thrombocytopenia, while in 11 patients the presentation of the disease was
      unusual. In the latter group, two neonates with PA initially appeared as a
      primarily hyperammonemic metabolic disease. In two other neonates the vomiting
      was so severe that they were diagnosed as intestinal obstruction in referral
      hospitals. The presentation in three infants was primarily as an immune disorder.
      In four infants, PA appeared as an acute or chronic encephalopathy, i.e. as a
      silent organic acidemia, with few other findings of the disease. The clinical
      picture of PA includes facial and nipple dysmorphia, severe hypotonia and
      vomiting. Severe thrombocytopenia is the hallmark of the metabolic crisis. In one
      patient it was noticed late and caused intracranial hemorrhage, while in three
      others intracranial bleeding caused death. The prognosis in PA remained grave
      despite rigorous treatment. Only seven of the 25 PA patients remained to have a
      normal life-style, while eight patients expired. The diagnosis is readily
      achieved by urine gas chromatography/mass spectrometry (GC/MS), by tandem mass
      spectrometry (MS/MS), or by enzyme analysis of fibroblasts. While there may be
      both examiner- and patient-related reasons for the variations in the presentation
      of PA, one other reason may be the heterogeneity of the molecular defect in
      propionyl-CoA carboxylase.

PMID- 7726382
TI  - A study of the response to protein-modified diets for propionic acidemia in
      twelve patients.
AB  - The charts of twelve patients with propionic acidemia (PA) were analyzed
      retrospectively for the outcome of dietary treatment. The diet was prescribed for
      each patient based on their individual needs. We established good diet compliance
      in four PA patients who were alive and well with healthy life-styles at the time
      of this report. The main difficulty causing non-compliance was the parents'
      inability to take care of the patient due to other family responsibilities. In
      two cases, the parents believed their children to be cured and they abandoned
      diet and medications, resulting in the sudden death of both children. In four
      cases, the parents were unable to cope with the demands of the diet and
      medications, while complications and severe classic PA provided no hope for two
      patients.

PMID- 7726383
TI  - 4-Hydroxybutyric aciduria.
AB  - The clinical findings in six patients from three families with 4-hydroxybutyric
      aciduria are described. The onset of disease was in early infancy in all cases.
      All infants presented with severe global delay and severe hypotonia, and all
      patients had seizure disorder. Eye findings included optic atrophy in two
      patients, and retinitis pigmentosa in one. Three patients had choreoathetosis,
      two had myoclonus and one had severe dystonia. The urine 4-hydroxybutyric acid
      was 300-1000 times that of normal, and other organic acids related to its further
      metabolism or to its inhibitory effect on beta-oxidation were also increased. The
      administration of vigabatrine rapidly reduced the excretion of 4-hydroxybutyric
      acid promptly, and in the long-term its excretion could be kept at 80-200 times
      that of normal. However, the clinical course of the disease improved in only two,
      remained the same in two, and worsened in the remaining two patients.

PMID- 7726384
TI  - The clinical spectrum of biotin-treatable encephalopathies in Saudi Arabia.
AB  - Ten patients with biotin-dependent, chronic progressive encephalopathies were
      studied retrospectively. In four patients, the underlying disease was either
      total or partial deficiency of biotinidase. In one patient, the disease was
      caused by a lack of holocarboxylase synthetase activity. Four patients presented
      with Leigh encephalopathy. However, a biochemical defect could not always be
      confirmed. All patients required the administration of large doses of biotin to
      maintain normal neurologic function.

PMID- 7726385
TI  - Comparative frequency and severity of hypoglycemia in selected organic acidemias,
      branched chain amino acidemia, and disorders of fructose metabolism.
AB  - The Institution's experience with hypoglycemia in different types of organic
      acidemias, branched chain amino acidemia (MSUD), and disorders of fructose
      metabolism was reviewed retrospectively. The charts of 144 patients who were
      followed for 1-5 years were studied for the severity and frequency of
      hypoglycemia. The patients were mainly Saudi; however, 10-25% were from
      neighboring countries. Therefore, the observations pertain to the genetic groups
      in the Arabian peninsula. Organic acidemias which primarily manifest with
      neurologic signs, such as 4-hydroxybutyric aciduria, infantile onset 3
      methylglutaconic aciduria, and glutaric aciduria type 1 never showed
      hypoglycemia. Patients with beta-ketothiolase deficiency, biotinidase deficiency,
      or intermittent or intermediate MSUD, also did not have hypoglycemia during
      metabolic crisis. Hypoglycemia was rare and mild among neonates with classic
      MSUD, ethylmalonic aciduria, and isovaleric acidemia. Less than 50% of the
      patients with MSUD older than 8 months, pyruvate carboxylase deficiency,
      methylmalonic acidemia, or propionic acidemia had hypoglycemia during metabolic
      crisis. On the other hand, patients with 3-hydroxy-3-methyl glutaryl-CoA lyase
      deficiency, holocarboxylase synthetase deficiency, medium or long-chain acyl-CoA
      dehydrogenase deficiency, neonatal onset 3-methylglutaconic aciduria, glutaric
      aciduria type 2, and disorders of fructose metabolism invariably had moderate-to
      severe hypoglycemia associated with metabolic crisis. The purpose of this report
      is to provide the pediatrician, particularly in the Middle East, with a
      diagnostic guideline to the identification and management of different types of
      organic acidemias, based on co-existing hypoglycemia.

PMID- 7726386
TI  - Emergency presentations of patients with methylmalonic acidemia, propionic
      acidemia and branched chain amino acidemia (MSUD).
AB  - The charts of 16 patients with branched chain amino acidemia (MSUD) who had 48
      emergency room (ER) visits, of 10 patients with propionic acidemia (PA) who had
      57 ER visit, and of 13 patients with methylmalonic acidemia (MMA) who had 154 ER
      visits, were reviewed retrospectively for the most common clinical presentations,
      physical and laboratory findings. The most common clinical presentation was acute
      or chronic vomiting and the most common physical finding was dehydration. When
      hypoglycemia was found, the mental status of 55% of patients with MSUD and MMA
      and 20% of patients with PA, was alert. Mixed acid/base disturbance, i.e.
      alkalosis caused by vomiting mixed with metabolic acidosis caused by the disease,
      was present in 30% of MSUD, in 33% of PA, and 45% of MMA. There was no
      relationship between acidosis detected by the blood pH and mental status of the
      patients. A good correlation between base excess < -5 and serum bicarbonate < 21
      mmol/l was found. Blood cultures were positive for bacteria and fungi in 15% of
      the visits with MSUD, in 23% with PA, and 3% with MMA. Patients with positive
      blood cultures did not necessarily have a temperature > 39 degrees C nor
      hypothermia. The results suggest that the mental status of the patients should
      not detract the ER physician from obtaining blood pH, gases and glucose and in
      all instances a blood culture should be secured, even if the patient has no
      fever.

PMID- 7726387
TI  - Movement disorders in childhood organic acidurias. Clinical, neuroimaging, and
      biochemical correlations.
AB  - Over the last 5 years the Pediatric Neurology service at King Faisal Specialist
      Hospital and Research Centre (KFSH&RC) has seen 131 infants and children with
      movement disorders. Forty-nine (37%) had identifiable biochemical defects, 25 of
      which were organic acidemias. Nineteen of 29 patients with dystonia had organic
      acidemias, primarily glutaric aciduria type 1 (7 patients), bilateral striatal
      necrosis (4 patients), and 3-methyl glutaconic aciduria (3 patients). All
      patients with parkinsonian rigidity (n = 11) had organic acidemias; again, the
      greatest number accounted for by glutaric aciduria type 1 (7 patients), who had
      both parkinsonian rigidity combined with dystonia. Myoclonus occurred in only 1
      of 25 and chorea in 7 of 25 patients with organic acidemias. At the least all
      patients had bilateral lesions of putamen and head of caudate, seen best in MRI
      brain scans as increased T2 signal intensities with normal volume, and later with
      volume loss.

PMID- 7726388
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- 7726389
TI  - Gap junctions in the rat cochlea: immunohistochemical and ultrastructural
      analysis.
AB  - Gap junctions in the rat cochlea were investigated using immunostaining for
      connexin26 and transmission electron microscopy. Electron microscopy of normal
      and pre-embedded immunostained material showed that there were gap junctions
      between and among all cells that light microscopy showed to have immunostained
      appositions. Light microscopy showed immunostaining between and among cell types
      that electron microscopy showed to be joined by gap junctions. Immunostaining for
      connexin26 was therefore taken as providing a reasonable approximation of the
      locations of gap junctions throughout the cochlea and was used to provide an
      overview of the extent of those locations. Cells interconnected via gap junctions
      fell into one of two groups. The first group consists of nonsensory epithelial
      cells and includes interdental cells of the spiral limbus, inner sulcus cells,
      organ of Corti supporting cells, outer sulcus cells, and cells within the root
      processes of the spiral ligament. The second group consists of connective tissue
      cells and includes various fibrocyte types of the spiral limbus and spiral
      ligament, basal and intermediate cells of the stria vascularis, and mesenchymal
      cells which line the scala vestibuli. The present work represents a first attempt
      towards a description of how serial gap junctions among cochlear cells reflect a
      level of organization of the tissue. The organization described here, together
      with a great deal of information from previous investigators, suggest that
      serially arranged gap junctions of both epithelial and connective tissue cells
      serve as the structural basis for recycling endolymphatic potassium ions that
      pass through the sensory cells during the transduction process.

PMID- 7726391
TI  - Early expression of chromogranin A and tyrosine hydroxylase during prenatal
      development of the bovine adrenal gland.
AB  - The present study was undertaken to define the temporal pattern and distribution
      of cells positive for chromogranin A (CgA) and tyrosine hydroxylase (TH) in
      various developmental stages of fetal bovine adrenal gland. CgA is an acidic
      protein, co-stored and co-released with amines and a variety of peptide hormones
      and neurotransmitters in dense core vesicles of neural and endocrine cells and
      can be used as a marker for these cells and their malignant counterparts. TH is
      the rate-limiting enzyme in catecholamine biosynthesis and reflects noradrenergic
      differentiation. The expression of CgA and TH was examined by
      immunohistochemistry. CgA immunoreactivity appears first in 35-day-old bovine
      fetuses. By the end of the second month, CgA-labelled cells are scattered
      throughout the entire primordium of the adrenal gland, and at a fetal age of 85
      91 days most of these cells concentrate in the developing adrenal medulla. From
      this stage onwards, immunoreactive cells of the marginal zone of the medulla
      exhibit significantly stronger CgA immunoreaction than the central area. TH
      immunoreactivity appeared in the adrenal primordium for the first time at the end
      of the second month of gestation. The distribution pattern of TH-positive cells
      was similar to that described for CgA, and no significant differences in
      topographical arrangement between TH- and CgA-positive cells can be detected. The
      results show that bovine adrenal chromaffin cells express CgA already during
      their earliest stages of development and prior to TH. The stronger immunoreaction
      of marginal adrenal medullary cells suggests an adrenalcortical effect of
      glucocorticoids on the expression of CgA.

PMID- 7726390
TI  - Ontogeny of somatostatin-immunoreactive systems in the brain of the brown trout
      (Teleostei).
AB  - The development of somatostatin-immunoreactive neurons and fibres was studied,
      using immunocytochemistry, in the brain of the brown trout. Somatostatinergic
      perikarya were found in many regions including several telencephalic areas, the
      preoptic nucleus, anterior tuberal and lateral tuberal nuclei, the lateral recess
      nucleus, dorsal tuberal nucleus, the pre- and pseudoglomerular nuclei, central
      thalamic nucleus, optic tectum, interpeduncular nucleus, several isthmal and
      reticular nuclei and the solitary fascicle nucleus. The ventrolateral area of the
      telencephalon and the nucleus lateralis tuberis are the first immunoreactive
      nuclei to appear in ontogeny, and cells of some telencephalic areas and of the
      lateral optic recess nucleus, the latest. Somatostatin-immunoreactive fibre
      tracts innervate the hypophysis and different regions of the brain. The most
      richly innervated areas in adults are the dorsolateral telencephalic area and the
      organon vasculosum laminae terminalis. Two patterns of production of
      somatostatinergic cells were observed: that of populations in which cell numbers
      increase over the lifetime of the fish, and that of populations whose cell number
      is established early in development or even diminishes in adulthood. These
      results provide interesting contrasts to those previously reported in birds and
      mammals.

PMID- 7726392
TI  - Microvascularization of the cerebellum in the turtle, Pseudemys scripta elegans
      (Reptilia). A scanning electron microscope study of microvascular corrosion
      casts, including stereological measurements.
AB  - Cerebellar blood supply and microvascular patterns were studied in 12 freshwater
      turtles Pseudemys scripta elegans by scanning electron microscopy (SEM) of
      microvascular corrosion casts and histology. Vascular densities were estimated by
      point counting methods from casts and thin sections (7 microns). Short A2
      arterioles and recurrent branches from A3-arterioles supply the capillary bed of
      the molecular layer, while V2 and V3 venules drain it. The Purkinje cell layer is
      supplied by horizontal branches ("parallel arteries") of A4 and A3 arterioles,
      which capillarize toward the granular and molecular layers. V2, V3 and V4 venules
      drain the areas supplied by A3 arterioles. The deep granular and subependymal
      layers are supplied by A4 arterioles, those adjacent to the Purkinje cell layer
      also by A3 arterioles. The areas supplied by A4 arterioles drain via V4 venules.
      The granular and Purkinje cell layers taken together have an estimated vascular
      density of 4.1%, while in the molecular layer this value is 3.3%. Our findings
      largely confirm published data from Testudo geometrica and Pseudemys scripta
      elegans with respect to gross supply and drainage. The microvascular patterns are
      similar to those of the human cerebellar cortex, particularly the basic patterns
      of intracortical arterioles and venules. The molecular layer, like that in the
      human brain, has a circulatory bed largely independent of that of the Purkinje
      cell and granular layers. In contrast to the human brain, a cerebellar pial
      capillary network is present in the brain of the turtle.

PMID- 7726393
TI  - Eye primordium transplantation in Xenopus embryo.
AB  - A part of the eye primordium, the presumptive retinal anlage, was transplanted
      from stage-23/24 Xenopus borealis to replace the removed olfactory anlage of
      Xenopus laevis. Cells of the two species can be distinguished under fluorescence
      microscopy, and we used the resulting chimeras to determine whether the
      transplanted eye primordium would inhibit the regeneration of the olfactory
      anlage, whether it would connect with its usual target, the diencephalon, and
      whether migration of cells would occur from the transplant to the host CNS or
      from the host CNS to the transplant. In all cases, the olfactory anlage
      regenerated promptly, and normal olfactory bulbs developed. Omission of the eye
      stalk in the transplant resulted in failure of an optic nerve to develop from the
      developing retina. A cellular bridge containing the optic axons connected the
      transplanted retina to the diencephalon. Cells from the transplant migrated
      freely through the cellular bridge to several CNS regions. Their morphology,
      topographic arrangement, number, and relations with other host elements are
      consistent with the hypothesis that these cells belong to both glia and neuron
      types.

PMID- 7726394
TI  - Cell migration from the transplanted olfactory placode in Xenopus.
AB  - The eye vesicle of Xenopus borealis has been replaced with the transplanted
      olfactory primordium from Xenopus laevis in an attempt to determine whether cells
      from the transplant could migrate along the regrowing olfactory nerve and become
      incorporated into the CNS of the host. The use of X. laevis and X. borealis pairs
      allowed us to distinguish the cells of the host from those of the donor at the
      cellular level by means of the characteristic fluorescent nuclear spots (Q bands)
      of X. borealis. Transplantation was performed on pairs of animals at stages
      23/24. The olfactory anlage was readily incorporated into the host, often fusing
      with the host homolateral organ and inhibiting the regrowth of the eye vesicle.
      An olfactory nerve developed from the transplanted organ. In the majority of
      cases, the nerve reached the diencephalon at the level of entrance of the optic
      nerve. Along the nerve originating from the transplanted organ we observed a
      stream of cells with the characteristics of the donor. These cells penetrated the
      host's CNS and became incorporated into it. The nature of these cells has not
      been ascertained by specific neuronal markers. However, on the basis of their
      morphology and disposition, the hypothesis suggested is that some of the
      migrating cells are neurons.

PMID- 7726395
TI  - Three-dimensional structure of the gustatory cell in the mouse fungiform taste
      buds: a computer-assisted reconstruction from serial ultrathin sections.
AB  - Taste buds in fungiform papillae of the mouse were examined with transmission
      electron microscopy and computer-assisted, three-dimensional reconstruction from
      serial ultrathin sections. In accord with observation by Murray (1971), four
      distinct cell types, type I, II, III and basal cells, were identified. Of these,
      only the type III cell made synaptic contacts with nerve terminals and contained
      both small, clear vesicles and dense-cored granules. The former vesicles were
      synaptic-type and accumulated in the cytoplasm just below the synaptic in
      membrane thickenings. This finding clearly indicates a sensory function for the
      type III cell. One to three type III cells were identified within a taste bud.
      The type III cell had at most eight synapses with nerve terminals. One nerve
      fiber making two synapses with the type III cell was occasionally observed in its
      terminal region.

PMID- 7726396
TI  - Postnatal migration of neurons and formation of laminae in rat cerebral cortex.
AB  - Migration of neurons and formation of laminae in the developing neocortex were
      studied by means of thymidine autoradiography. Timed pregnant rats received a
      single pulse injection of [3H]thymidine in the morning of embryonic day (E)13,
      14, 15, 16, 17, 18 or 19. Pups were killed on postnatal day (P)0, 1, 2, 3, 4, 6,
      10, 30, or 60 and brains were processed for autoradiography. Neurons in posterior
      (visual) cortical areas labeled by [3H]thymidine administration on E13 or E14
      were found predominantly in the cortical subplate; cells labeled on E15 in layer
      VI; cells labeled on E16 in layers VI and V, cells labeled on E17 in layers V and
      IV; E18 in layers IV and III; and E19 in layers III and II. By the day of birth
      (P0), neurons labeled from E13-16 injections were already in their mature laminae
      in cortex. Many of the cells labeled on E17 were still situated within the cell
      dense cortical plate (CP) at P0, and within layer V by P1. Cells labeled on E18
      were found in the most superficial part of the CP on P0, in the deep part of the
      CP on P1, and formed layer IV on P2 and P3. At P0, many E19 labeled cells
      appeared to be in migration to the cortex and were found in the CP on P1, in
      layer III by P4, and in layer II by P6. Cells in the auditory cortex labeled by
      [3H]thymidine injections on a particular day were situated more superficially
      than comparable labeled cells in the visual cortex, indicating a lateral to
      medial gradient in which the auditory cortex is formed earlier than the visual
      cortex. Distributions of labeled cells in the somatosensory cortex were similar
      to those in the visual cortex. These data provide a detailed and comprehensive
      description of the position of varied populations of cortical neurons during the
      early postnatal period, as well as a description of the formation of cortical
      laminae at times when major systems of afferents are growing into the cortex and
      making synaptic connections with their target cells.

PMID- 7726397
TI  - Arterial and jugular venous bulb blood propofol concentrations during induction
      of anesthesia.
AB  - The aim of this study was to show that blood propofol concentrations at loss of
      consciousness vary with the rate of administration. Eighteen patients were
      allocated to receive a propofol infusion at 6 or 12 mg.kg-1.h-1 (approximately 8
      and 15 mg/min) for induction of anesthesia. Propofol concentrations were analyzed
      from simultaneous arterial and jugular bulb venous blood samples. There were no
      significant differences in the dose of propofol administered to induce anesthesia
      (0.52 mg/kg both groups). However there were significant differences between the
      groups in the mean induction times (309 and 156 s), and in median arterial and
      venous concentrations at induction. Arterial concentrations were 1.93 and 2.70
      and venous 1.11 and 1.51 micrograms/mL. There were no significant differences
      between the groups in the area between the arterial and venous time concentration
      curves from start of infusion to loss of consciousness (3.14 and 3.05
      micrograms.mL-1.min-1). This study confirms that a target blood concentration of
      propofol cannot be identified with loss of consciousness under nonsteady state
      conditions. Both arterial and venous blood propofol concentrations at loss of
      consciousness depend on the rate of administration.

PMID- 7726398
TI  - Mild hypothermia alters propofol pharmacokinetics and increases the duration of
      action of atracurium.
AB  - Mild intraoperative hypothermia is common. We therefore studied the effects of
      mild hypothermia on propofol pharmacokinetics, hepatic blood flow, and atracurium
      duration of action in healthy volunteers. Six young volunteers were studied on
      two randomly assigned days, at either 34 degrees C or 37 degrees C. Anesthesia
      was induced with thiopental, 3 mg/kg, and maintained with 70% N2O and 0.6%
      isoflurane. Core hypothermia was induced by conductive and convective cooling. On
      the other study day, normothermia was maintained by a Bair Hugger (Augustine
      Medical, Inc., Eden Prairie, MN) forced-air warmer. Propofol, 1 mg/kg lean body
      mass (LBM), then was given, followed by a 4-h infusion at 5 mg.kg-1.h-1. After 2
      h, atracurium 0.5 mg/kg was administered as an intravenous bolus. Indocyanine
      green was administered for estimation of hepatic blood flow. Arterial blood was
      assayed for propofol and indocyanine green concentration. Pharmacokinetic
      analysis was performed using NONMEM. Results are reported as means +/- SEM.
      Propofol blood concentrations averaged approximately 28% more at 34 degrees C
      than at 37 degrees C (P < 0.05). Hepatic blood flow decreased 23% +/- 11% in
      normothermic volunteers during the propofol infusion, and 33% +/- 11% in
      hypothermic volunteers (P = not significant). A three-compartment mamillary model
      fitted the data best. Inclusion of hepatic blood flow change from the prepropofol
      baseline as a covariate for total body clearance significantly improved the fit.
      The intercompartmental clearances were decreased in the presence of
      hypothermia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726401
TI  - Epidural hematoma after epidural anesthesia in a patient with hepatic cirrhosis.

PMID- 7726399
TI  - Postoperative ischemic optic neuropathy.

PMID- 7726400
TI  - Intrathecal buprenorphine in the treatment of phantom limb pain.

PMID- 7726402
TI  - Bilateral postpartum femoral neuropathy.

PMID- 7726403
TI  - Sudden decreases in mixed venous oxygen saturation during posterior spinal
      fusion.

PMID- 7726404
TI  - Helium/oxygen breathing improved hypoxemia after cardiac surgery: case reports.

PMID- 7726405
TI  - Hyponatremic encephalopathy after rollerball endometrial ablation.

PMID- 7726406
TI  - Probable venous air embolism associated with removal of the Mayfield skull clamp.

PMID- 7726407
TI  - A case of tracheomalacia during isoflurane anesthesia.

PMID- 7726408
TI  - Dantrolene treatment for abrupt intrathecal baclofen withdrawal.

PMID- 7726409
TI  - Allergic reaction to latex from stopper of a medication vial.

PMID- 7726410
TI  - Effect of topical eutectic mixture of local anesthetics on pain response and
      analgesic requirement during extracorporeal shock wave lithotripsy.

PMID- 7726411
TI  - Simple aspiration of a pneumothorax utilizing a triple-lumen catheter.

PMID- 7726412
TI  - Management of meralgia paresthetica: a multimodality regimen.

PMID- 7726413
TI  - Fluid warmer as a potential source of air bubble emboli.

PMID- 7726414
TI  - Nasopharyngeal airway for guiding nasogastric tubes: not the best choice.

PMID- 7726415
TI  - An easy-to-perform test to help confirm intravascular placement of pediatric
      intravenous lines.

PMID- 7726416
TI  - The effect of pregnancy on the plasma protein binding of lidocaine: does it
      matter?

PMID- 7726418
TI  - Epidural pump failure.

PMID- 7726417
TI  - Oral clonidine premedication does not affect preoperative gastric fluid pH and
      volume in children.

PMID- 7726419
TI  - Yes, put on gloves, but also take them off.

PMID- 7726420
TI  - Partial airway obstruction after lingual frenotomy.

PMID- 7726421
TI  - Pain on injection of rocuronium bromide.

PMID- 7726422
TI  - Walk, don't run: alternative methods of changing needle direction.

PMID- 7726423
TI  - Dual causes of vaporizer aberrance lucidly separated.

PMID- 7726424
TI  - When is testing the test dose the wrong thing to do?

PMID- 7726425
TI  - The hemodynamic responses to an intravenous test dose in vascular surgical
      patients.
AB  - The study was designed to investigate the hemodynamic responses to intravenous
      (IV) injections of various epidural test doses in vascular surgical patients to
      determine whether previously established criteria in healthier populations were
      valid in this inherently sicker population. A double-blind, prospective
      randomized study was performed on 50 patients, not receiving beta-adrenergic
      antagonists, presenting for vascular surgery and requiring an arterial line.
      Patients were randomly assigned to receive a 3-mL injection of one of five
      solutions, either saline (Group 1), lidocaine 45 mg (Group 2), lidocaine 45 mg
      and epinephrine 5 micrograms (Group 3), lidocaine 45 mg and epinephrine 10
      micrograms (Group 4), or lidocaine 45 mg and epinephrine 15 micrograms (Group 5).
      After injection, a blinded observer recorded arterial blood pressure and heart
      rate (HR) every 15 s for 3 min. The changes in HR, systolic (SBP), mean (MBP),
      and diastolic (DBP) blood pressure as well as time to maximum change were
      analyzed both within and between groups. Only Group 5 had significant within
      group changes for all hemodynamic variables measured. Only in the comparison
      between Groups 1 and 5 and between Groups 2 and 5 were there significant changes
      in both HR and SBP. The mean increase in HR and SBP within Group 5 was 17.0 +/-
      5.9 bpm and 31.0 +/- 10.5 mm Hg, respectively. No differences were found between
      groups for time to maximum change for HR and SBP which for Group 5 were 64.5 +/-
      37.4 s and 90.0 +/- 56.7 s, respectively. To achieve 100% sensitivity and
      specificity for HR increase, the criterion established was > or = 9 bpm.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7726427
TI  - Fibrous structures in the subarachnoid space: a study with spinaloscopy in
      autopsy subjects.
AB  - The lumbar and lower thoracic subarachnoid space of 26 human autopsy subjects was
      studied using rigid endoscopy, spinaloscopy. Fibrous attachments were found
      between nerve roots and/or nerve roots and the arachnoid membrane at least at one
      spinal level in 16 subjects. The appearance and density of the structures varied,
      and caused restriction of nerve root mobility in nine subjects. In three of them,
      the impeded mobility prevented the nerve root from yielding to the contact and
      pressure exerted either by the tip of the endoscope or by a spinal needle
      introduced into the subarachnoid space. In another three subjects, a distinct
      membranous structure was identified in the posterior midline of the subarachnoid
      space in the lower thoracic and upper lumbar regions. These findings may possibly
      be associated with the variation in the extent of subarachnoid block and to the
      development of isolated nerve root trauma in connection with this procedure.

PMID- 7726426
TI  - Analgesic and hemodynamic effects of epidural clonidine, clonidine/morphine, and
      morphine after pancreatic surgery--a double-blind study.
AB  - This study characterizes analgesia an hemodynamics after epidural clonidine 8
      micrograms/kg (Group C) or clonidine 4 micrograms/kg+morphine 2 mg (Group CM) in
      comparison to epidural morphine 50 micrograms/kg (Group M). Forty-five patients
      scheduled for pancreatectomy in combined general/epidural anesthesia were
      studied. The study drugs were administered 75 min postoperatively and for 10 h
      pain intensity (visual analog scale [VAS]), heart rate (HR), mean arterial
      pressure (MAP), and cardiac output (CO) were measured; filling pressures were
      kept > 5 mm Hg. Adequate analgesia could be achieved within 1 h in all patients
      of Groups C and CM, but only in six patients of Group M (P < 0.001). Quality of
      analgesia was comparable in all groups (VAS reduction 82% +/- 20%, mean +/- SD)
      but duration of analgesic action was longer in Groups CM (586 +/- 217 min) and M
      (775 +/- 378 min) compared to Group C (336 +/- 119 min) (P < 0.001). In Group M,
      no hemodynamic alterations occurred. In Groups C and CM, HR, CO, and MAP were
      reduced significantly compared to baseline within the first 15-90 min, while
      stroke volume and systemic vascular resistance remained stable. We conclude, that
      hemodynamic alteration after epidural clonidine under conditions of stable
      filling pressures is caused mainly by a decrease in HR. It is not an effect of
      analgesia but of the intrinsic antihypertensive action of clonidine.

PMID- 7726428
TI  - A prospective study of the feasibility of continuous spinal anesthesia in a
      university hospital.
AB  - A prospective study was undertaken in an elderly population undergoing orthopedic
      surgery to specifically study the feasibility of continuous spinal anesthesia
      (CSA). In a university hospital, 14 residents and 5 junior staff, using an 18
      gauge needle and a 20-gauge catheter, performed 76 and 24 consecutive CSAs,
      respectively. There was an overall failure rate of 6%, all occurring in the
      residents' group. The causes affecting the success of CSA were inability to
      identify the subarachnoid space in 5/6 cases (all lumbar punctures were performed
      using the midline approach) and, in one case, inability to thread the catheter.
      The six failed CSAs were ultimately performed successfully by one of the senior
      authors. All surgeries were successfully performed with CSA, without requiring
      general anesthesia or intravenous narcotic supplementation. Anesthesia was
      initiated with isobaric bupivacaine in 94/100 cases. In 18% of patients,
      inadequate anesthesia prompted modifications of the local anesthetic solutions
      (i.e., type, baricity, total dosage) before surgery. One case of minor neurologic
      complication was observed, but no postspinal headache occurred. In conclusion,
      our findings led us to pursue CSA with large-bore equipment in an elderly
      population; furthermore, we believe that teaching the earlier use of alternative
      approaches other than the midline approach could further reduce our failure rate.

PMID- 7726429
TI  - Antinociception induced by simultaneous intrathecal and intraperitoneal
      administration of low doses of morphine.
AB  - The application of morphine simultaneously into the spinal cord and brain
      ventricles produces a supraadditive antinociceptive effect. In this study, we
      attempted to determine whether combined intrathecal (IT) and intraperitoneal (IP)
      administration of small doses of morphine also produces such a synergistic
      antinociceptive effect. The experiments were performed on male Wistar rats.
      Nociception was measured using the tail immersion test. For IT administration
      morphine was injected through a catheter implanted in the subarachnoid space.
      Combined administration of small doses of IT (1 microgram) and IP (1 mg/kg)
      morphine resulted in a strong, highly significant antinociceptive effect. This
      effect was not only much higher than that produced by separate administration of
      the same doses of morphine, but also much higher than the expected effect of the
      combination. These results demonstrate that low doses of IT and IP morphine
      interact in a supraadditive fashion to produce potent analgesia.

PMID- 7726430
TI  - Activity changes in rat raphe magnus neurons at different concentrations of
      fentanyl in vitro.
AB  - The nucleus raphe magnus (NRM) is an important descending pain inhibitory system.
      We postulated that the analgesic action of supraspinally administered opiates
      results from increased descending inhibitory control of the NRM. We tested
      whether fentanyl activates NRM neurons in the rat slice preparation using extra
      cellular recording. Eighty-seven percent of NRM neurons (total number = 68)
      tested were spontaneously active with firing frequencies of 0.2-4 spikes/s in
      artificial cerebrospinal fluid. Application of fentanyl (0.25, 0.5, and 1
      mumol/L) increased firing frequencies in 12 of 59 (20%) spontaneously active
      neurons. In 6 of 9 (67%) silent neurons, fentanyl induced firing activities.
      Naloxone (1-2 mumol/L) antagonized the increased or induced activities by
      fentanyl in three neurons. In 13 of 59 (22%) spontaneously active neurons,
      fentanyl decreased the firing frequencies. Although fentanyl was associated with
      increased activity in a total of 18 NRM neurons, fentanyl at a higher
      concentration significantly increased the number of inhibited neurons. The
      results indicate that fentanyl partly activates the descending inhibitory system
      originating from the NRM; however, at higher concentrations, it appears also to
      inhibit this same system.

PMID- 7726431
TI  - Recovery pattern and home-readiness after ambulatory surgery.
AB  - Despite increased use of ambulatory surgery, few data exist regarding patient
      recovery patterns and home-readiness. We prospectively identified the pattern of
      home-readiness, the persistent symptoms after surgery, and the factors that delay
      discharge after home-readiness criteria are satisfied. Five hundred patients were
      scored by the same investigator using the Postanesthetic Discharge Scoring System
      (PADSS) every 30 min, commencing 30 min after surgery, until the PADSS score was
      > or = 9. The same investigator telephoned each patient 24 h after discharge to
      administer a standardized questionnaire so that postoperative symptoms could be
      identified. Eighty-two percent of patients were discharged 2 h and 95.6% 3 h
      after surgery. These patients could have been discharged earlier. After home
      readiness criteria were satisfied, some patients had delayed discharge because of
      the unavailability of immediate escorts or the recurrence of pain. Persistent
      symptoms delaying discharge occurred in 4.4% of patients. Patients who underwent
      certain ambulatory surgical procedures, such as laparoscopy or orthopedic and
      general surgery, had a sixfold increased risk of developing persistent symptoms
      in the ambulatory surgery unit. The time to home-readiness was 2.5-fold longer
      and the incidence of 24-h postoperative symptoms, two- to eightfold higher in the
      group with persistent symptoms in the ambulatory surgery unit. In summary,
      periodic objective evaluation of home-readiness revealed that the majority of
      patients would achieve a satisfactory score on or before 2 h after surgery. The
      time to home-readiness by objective evaluation correlated with the type of
      surgery. Most delays after satisfactory home-readiness scores were reached were
      due to nonmedical reasons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726432
TI  - Postoperative nausea and vomiting after discharge from outpatient surgery
      centers.
AB  - We examined patients' experiences with nausea and vomiting after they were
      discharged from outpatient surgical centers. Data were collected on 211 surgical
      outpatients at 24-48 h after discharge via a telephone interview conducted by
      outpatient surgery nurses, and at 5 days after discharge via a patient-completed
      questionnaire. Telephone interviews were conducted with 193 patients.
      Questionnaires were completed by 154 patients. Over 35% of patients experienced
      postdischarge nausea and vomiting. Most had not experienced nausea and vomiting
      in the recovery room. The severity of nausea for these patients averaged 5 on a
      10-point scale (10 indicating very severe nausea). During the 5 days after
      discharge, these patients reported experiencing nausea for an average of 1.7 days
      and vomiting for 0.7 days. Patients who experienced postdischarge nausea and
      vomiting were not able to resume their normal daily activities as quickly as
      those who did not. Patients managed postdischarge nausea and vomiting with little
      contact or intervention from health professionals and with minimal product
      purchases. The results indicate that postdischarge nausea and vomiting is common
      after outpatient surgery, and that it results in substantial distress and
      impairment for patients who experience it.

PMID- 7726433
TI  - Does hemoglobin concentration affect perioperative myocardial lactate flux in
      patients undergoing coronary artery bypass surgery?
AB  - Increasing concern over complications related to blood transfusions has prompted
      a reevaluation of what constitutes an "adequate" perioperative hemoglobin
      concentration, particularly in patients undergoing coronary artery bypass graft
      (CABG) surgery. Data from 224 patients with preserved ventricular function
      (ejection fraction > 50%), undergoing CABG surgery, previously studied under a
      variety of anesthetic protocols, were reexamined to determine the effect of
      hemoglobin (HGB) concentration on myocardial lactate flux (MLF) (as an index of
      ischemia). The interaction of MLF and HGB concentration, anesthetic technique
      (ANES), and hemodynamic variables (including systemic and pulmonary arterial
      pressures (SAP and PAP), cardiac output (CO), and myocardial oxygen consumption
      (MVO2) was determined from a pool of 1598 data sets obtained from 224 patients.
      Data were collected from just prior to induction of anesthesia until 24 h
      postoperatively. Univariate analysis revealed a statistically significant
      relationship between MLF and HGB concentration (P < 0.001) but the correlation
      coefficient was only 0.09. Multiple regression analysis did not determine HGB
      concentration to be a significant independent term affecting MLF in either the
      overall group or in a subgroup of 22 patients having an adverse outcome
      (myocardial infarction, stroke, or death). For patients undergoing CABG surgery,
      HGB concentrations within the range of 58-172 g/L were not a significant variable
      in production of global myocardial ischemia as evidenced by MLF. This suggests
      that HGB concentrations as low as 60-70 g/L in the perioperative period are well
      tolerated and are not associated with an increased incidence of myocardial
      ischemia.

PMID- 7726434
TI  - Additive cardiac depression by volatile anesthetics in isolated hearts after
      chronic amiodarone treatment.
AB  - Some patients undergoing general anesthesia may be chronically receiving the
      antidysrhythmic drug amiodarone. The half-life of this drug is very long and it
      may not be advisable or possible to discontinue its administration prior to
      anesthesia. We examined depressant effects of three volatile anesthetics in
      hearts isolated from guinea pigs chronically treated with amiodarone. Hearts were
      isolated and perfused retrogradely through the aorta with oxygenated Krebs-Ringer
      solution at 37 degrees C at constant pressure. Variables measured in 26 hearts
      were heart rate (HR), atrioventricular, intraatrial, and intraventricular
      conduction times (AVCT, IACT, IVCT) during pacing at 240 bpm, coronary flow, and
      left ventricular pressure (LVP). Amiodarone (20 mg intraperitoneally) or placebo
      (Group 1) was given once daily for 1 (Group 2) or 4 (Group 3) wk. Cardiac tissue
      concentrations of amiodarone were similar (12.1 micrograms/g wet weight) in
      hearts in Groups 2 and 3 but serum levels were twice as high in hearts in Group 3
      as in Group 2 (0.33 vs 0.17 microgram/mL). Before anesthetic exposure, all
      variables for hearts in Group 2 were not significantly different from those in
      Group 1. Significantly, for hearts in Group 3, compared to those in Group 1, HR
      was slower (-14%), conduction times were longer (IACT + 5 ms, IVCT + 4 ms, AVCT +
      9 ms), coronary flow was higher (+23%), and LVP was lower (-12%). After control
      measurements, hearts were exposed to 0.5 and 1 minimum alveolar anesthetic
      concentration (MAC) halothane, enflurane, and isoflurane in random
      order.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726435
TI  - Etomidate reduces ischemia-induced glutamate release in the hippocampus in rats
      subjected to incomplete forebrain ischemia.
AB  - Etomidate and thiopental reduce ischemic neuronal injury but the mechanism by
      which they do so is not clear. Ischemia-induced release of the excitatory
      neurotransmitters glutamate and glycine is thought to play a major role in the
      pathophysiology of ischemic injury. To determine how etomidate and thiopental
      modulate excitatory transmitter release, their effect on the release of glycine
      and glutamate during ischemia was evaluated by microdialysis in the hippocampus
      and cortex of rats. Three groups of Wistar-Kyoto rats (n = 5/group) were studied.
      In the etomidate and thiopental groups, electroencephalogram (EEG) burst
      suppression was achieved and maintained by a continuous infusion of either
      etomidate (0.6 mg.kg-1.min-1) or thiopental (3 mg.kg-1.min-1) 40 min prior to
      ischemia. Halothane anesthetized (1 minimum alveolar anesthetic concentration
      [MAC]) rats served as controls. Ischemia was induced in all three groups by
      bilateral carotid artery occlusion with simultaneous hypotension to 35 mm Hg for
      10 min. Pericranial temperature was controlled at 38 degrees C. Dialysate was
      collected before, during, and after ischemia. The levels of glutamate and glycine
      in the dialysate were measured by high-performance liquid chromatography. Within
      the hippocampus, both glutamate and glycine levels increased significantly in the
      thiopental and control groups. By contrast, in the etomidate group, glutamate and
      glycine levels did not increase during ischemia, and peak levels were
      significantly less than those in the thiopental group. Peak glutamate levels in
      the thiopental group were significantly larger than in the control group, whereas
      the peak glycine levels were not different among the groups.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7726436
TI  - Effects of sevoflurane on the middle latency auditory evoked response and the
      electroencephalographic power spectrum.
AB  - We investigated the effects of sevoflurane on the middle latency auditory evoked
      response (MLR) and the power spectrum of the electroencephalogram (EEG) in 10
      elective surgical patients. The MLR and the EEG power spectrum were recorded with
      a surface electrode placed at the central (Cz) scalp location. End-tidal
      sevoflurane concentrations of 0%, 0.25%, 0.5%, 0.75%, 1.0%, and 1.5% in 50%
      nitrous oxide and oxygen were studied. The Na, Pa, and Nb components of the MLR
      increased in latency and decreased in amplitude in a dose-dependent manner at
      increasing concentrations of sevoflurane. The latencies for Na, Pa, and Nb
      increased in a linear fashion (correlation coefficients: r = 0.81, r = 0.81, and
      r = 0.89, respectively). The EEG delta power was dominant with increasing
      sevoflurane concentration, and was significantly increased at sevoflurane
      concentrations of 1.0%-1.5%. The beta power, median power frequency (MPF), and
      95% spectral edge frequency (SEF) decreased significantly according to the
      increases by 0.5% sevoflurane. Regarding the changes evoked by 0.25% sevoflurane,
      the Nb latency of the MLR responded significantly under 0.75% of sevoflurane. At
      these low concentrations of sevoflurane, the MLR seemed to be more sensitive to
      changes in anesthetic concentration than the various EEG variables.

PMID- 7726437
TI  - SCH 32615, an enkephalinase inhibitor, enhances pregnancy-induced analgesia in
      mice.
AB  - Increased tolerance to noxious stimuli during pregnancy has been demonstrated.
      The purpose of this study was to examine the effect of SCH 32615, an inhibitor of
      one of the enzymes (enkephalinase) responsible for the degradation of endogenous
      enkephalins, on pregnancy-induced analgesia in mice. Analgesia was tested using
      the hot-plate and tail-flick tests. For the hot-plate test, animals were tested
      in late pregnancy (Day 17 or Day 18 of pregnancy; mice deliver on Day 19) and in
      the postpartum period (Days 2 and 8 after delivery) in the following groups: i)
      no treatment (n = 15); ii) vehicle only (n = 15); iii) SCH 32615 250 mg/kg (n =
      20), 150 mg/kg (n = 15), 50 mg/kg (n = 14); iv) naloxone 5 mg/kg (n = 15); v)
      naloxone 5 mg/kg+SCH 32615 150 mg/kg (n = 10); vi) nonpregnant control given SCH
      32615 150 mg/kg (n = 14). All drugs were given subcutaneously. Hot-plate latency
      (HPL) was significantly higher in pregnant mice (mean hot-plate latency 17.5 s)
      than postpartum mice (mean hot-plate latency 11 s on Day 2 and 8.5 s on Day 8).
      SCH 32615 250 mg/kg and 150 mg/kg significantly enhanced this analgesia in
      pregnant mice (mean percent of maximum possible effect 24.2 and 29.9,
      respectively) but not SCH 32615 50 mg/kg or the vehicle alone (mean percent of
      maximum possible effect 12.4 and 0.5, respectively). Naloxone significantly
      lowered HPL in pregnant mice (19.8 s-16.2 s) and antagonized the effect of SCH
      32615.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726438
TI  - The prone positioning during general anesthesia minimally affects respiratory
      mechanics while improving functional residual capacity and increasing oxygen
      tension.
AB  - We investigated the effects of the prone position on the mechanical properties
      (compliance and resistance) of the total respiratory system, the lung, and the
      chest wall, and the functional residual capacity (FRC) and gas exchange in 17
      normal, anesthetized, and paralyzed patients undergoing elective surgery. We used
      the esophageal balloon technique together with rapid airway occlusions during
      constant inspiratory flow to partition the mechanics of the respiratory system
      into its pulmonary and chest wall components. FRC was measured by the helium
      dilution technique. Measurements were taken in the supine position and after 20
      min in the prone position maintaining the same respiratory pattern (tidal volume
      10 mL/kg, respiratory rate 14 breaths/min, FIO2 0.4). We found that the prone
      position did not significantly affect the respiratory system compliance (80.9 +/-
      16.6 vs 75.9 +/- 13.2 mL/cm H2O) or the lung and chest wall compliance.
      Respiratory resistance slightly increased in the prone position (4.8 +/- 2.5 vs
      5.4 +/- 2.7 cm H2O.L-1.s,P < 0.05), mainly due to the chest wall resistance (1.3
      +/- 0.6 vs 1.9 +/- 0.8 cm H2O.L-1.s, P < 0.05). Both FRC and PaO2 markedly (P <
      0.01) increased from the supine to the prone position (1.9 +/- 0.6 vs 2.9 +/- 0.7
      L, P < 0.01, and 160 +/- 37 vs 199 +/- 16 mm Hg, P < 0.01, respectively), whereas
      PaCO2 was unchanged. In conclusion, the prone position during general anesthesia
      does not negatively affect respiratory mechanics and improves lung volumes and
      oxygenation.

PMID- 7726439
TI  - Ventilatory effects, blood gas changes, and oxygen consumption during
      laparoscopic hysterectomy.
AB  - We evaluated the ventilatory effects and blood gas changes of prolonged CO2
      pneumoperitoneum in nor-moventilated patients and examined the respiratory and
      gas exchange consequences of head-down positioning (25-30 degrees) and CO2
      insufflation into the peritoneal cavity in 20 patients without major
      cardiorespiratory disorders in various phases of laparoscopic hysterectomy. The
      patients received general anesthesia with isoflurane, fentanyl, and vecuronium,
      and minute ventilation (MV) was adjusted to maintain the PETCO2 at 33-36 mm Hg
      throughout the entire procedure, either by increasing the tidal volume (TV) and
      keeping the respiratory rate (RR) at 12/min (10 patients) or by changing the RR
      and maintaining the TV at 8 mL/kg (10 patients). Arterial and mixed venous blood
      samples were collected simultaneously for blood gas analysis and for measurements
      of oxygen consumption, and respiratory mechanics and gases were recorded by an
      anesthetic gas analyzer and side stream spirometry device. Oxygen consumption
      decreased with anesthesia, remained stable to the end of the laparoscopy,
      increased soon after deflation of the pneumoperitoneum, and reached preanesthetic
      values during recovery. The MV requirement increased by approximately 30% after
      the start of CO2 insufflation, then increased somewhat further toward the end of
      the laparoscopy, reaching the highest level a few minutes after deflation of the
      intraabdominal gas. The compliance decreased by 20% with the head-down position
      and by an additional 30% with the increased intraabdominal pressure. PaCO2 and
      mixed venous PCO2 increased with CO2 insufflation, and the arterial to end-tidal
      PCO2 (a-etPCO2) gradient increased by 1.5 mm Hg during laparoscopy. A mild
      metabolic acidosis developed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726440
TI  - The influence of propofol on vomiting induced by apomorphine.
AB  - It has been proposed that propofol has antiemetic effects even in nonsedative
      doses. The aim of this study was to investigate whether propofol influences
      vomiting induced by the dopamine agonist apomorphine. Ten healthy male volunteers
      received apomorphine infusion (1 mg/min) until vomiting was induced on four
      different occasions in a randomized order: a) during propofol infusion (2.4 +/-
      0.7 mg.kg-1.h-1, mean +/- SD) at a sedation score of Grade 2-3 on a 5-grade
      scale; b) during midazolam infusion (0.13 +/- 0.04 mg.kg-1.h-1) at a sedation
      score of Grade 2-3 on a 5-grade scale; c) after a single nonsedating bolus dose
      propofol 0.4 mg/kg; and d) during infusion of normal saline. The amount of
      apomorphine needed to induce vomiting was increased after sedation with propofol
      (P = 0.005) as well as midazolam (P = 0.001). There was no difference in the
      sensitivity to apomorphine between these sedative regimens. The nonsedating
      single bolus propofol did not change the sensitivity to apomorphine compared to
      the saline infusion. We conclude that propofol given in a nonsedative dose has no
      effect on apomorphine-induced vomiting. However, the total amount of apomorphine
      given to induce vomiting was significantly larger during propofol sedation than
      during saline infusion. This was probably an effect of sedation inasmuch as a
      similar result was achieved during midazolam sedation.

PMID- 7726441
TI  - The antiemetic efficacy of prophylactic granisetron in gynecologic surgery.
AB  - Postoperative nausea and vomiting are common after recovery from anesthesia. We
      examined the prophylactic effect of granisetron on postoperative nausea and
      vomiting in 120 female patients (ASA physical status I) undergoing gynecologic
      surgery. They were randomly allocated to one of three groups (n = 40 for each):
      saline (as a control), granisetron 20 micrograms/kg, and granisetron 40
      micrograms/kg. Saline or granisetron was given intravenously (IV) over 5 min
      approximately 30 min before the end of anesthesia. Nausea, vomiting, and safety
      assessments were performed during the 24-h recovery period. For the 24-h period
      after surgery, the number of emesis-free patients was significantly larger in the
      granisetron groups than in the control group (83%, 78%, and 20% of patients
      receiving granisetron 20 micrograms/kg and 40 micrograms/kg, and saline,
      respectively). Granisetron at both doses also was superior to the control for the
      prevention of nausea over the 24-h study period (nausea visual analog scales at
      24-h postsurgery: 49 mm, 17 mm, and 18 mm in the control, granisetron 20
      micrograms/kg, and granisetron 40 micrograms/kg groups, respectively). Fewer
      patients received "rescue" antiemetics in the granisetron groups than in the
      control group (10%, 10%, and 43% of patients in granisetron 20 micrograms/kg and
      40 micrograms/kg, and the control groups, respectively). The adverse events in
      the granisetron groups were similar to those in the control group. The
      administration of granisetron had no significant effect on vital signs or
      clinical laboratory test profiles. Granisetron given at 20 or 40 micrograms/kg
      i.v. during anesthesia appears to be a simple, effective, and safe method for
      preventing postoperative nausea and vomiting.

PMID- 7726442
TI  - The time course of gastric pH changes induced by omeprazole and ranitidine: a 24
      hour dose-response study.
AB  - The time-course of the effects of single-dose acid-reducing therapy in surgical
      patients is not known. Therefore, a prospective, randomized trial compared the
      effects of single-dose administration of omeprazole or ranitidine on gastric pH
      in 52 patients undergoing lower abdominal surgery. The two drugs were
      administered intravenously in random fashion after placement of a gastric
      electrode for continuous 24-h pH monitoring In patients receiving omeprazole 20
      mg (n = 13) and 40 mg (n = 13), gastric pH > or = 2.5 was achieved after a median
      of 80 (range 15-269) min and 40 (6-102) min (P = not significant [NS]), whereas
      in those receiving ranitidine 25 mg (n = 13) and 50 mg (n = 13), this pH was
      reached after a median of 32 (15-82) and 44 (16-84) min, respectively (P = NS).
      Over the first 24 h postoperatively, gastric pH remained less than 2.5 for a
      significantly longer time (1060 min vs 611 min), and more than 4.0 for a
      significantly shorter time (240 min vs 780 min) after omeprazole 20 mg than after
      ranitidine 50 mg. There were no other significant differences among treatment
      groups regarding the duration of gastric pH less than 2.5, between 2.5 and 4.0,
      and more than 4.0. In all treatment groups, the gastric pH returned to the
      baseline value of < 2.0 within 18 h. We conclude that when it is desired that
      gastric pH be more than 4.0 for at least 3 h, a single dose of ranitidine 25 mg
      or 50 mg should be administered 30-45 min prior to induction of anesthesia.

PMID- 7726443
TI  - The incidence of gastroesophageal reflux with the laryngeal mask: a comparison
      with the face mask using esophageal lumen pH electrodes.
AB  - To test the hypothesis that the laryngeal mask airway (LMA) predisposes patients
      to gastroesophageal reflux, we randomly assigned 55 patients having elective
      surgery to receive standardized anesthesia with the LMA or with conventional face
      mask (FM) plus airway. A pH-sensitive probe with two electrodes, 10 cm apart, was
      passed nasally into the esophagus 1 h before induction of anesthesia, and
      recordings were made continuously until 30 min after surgery. At the distal
      electrode, 30 cm from the anterior nares, there was a significant difference in
      the incidence of reflux: 53.6% with the LMA versus 22.2% with the FM (P < 0.05).
      At the level of the proximal electrode, 20 cm from the anterior nares, there was
      no difference between groups. Multiple reflux events, defined as two or more
      reflux events before, during, or after anesthesia, were significantly more
      frequent in the LMA group (P < 0.05). Reflux events continued in the
      postanesthesia care unit (PACU) in both groups with no significant difference
      between groups. There was no clinical evidence of aspiration of gastric contents
      in either group. Use of the LMA appears to result in increased reflux to the
      level of the mid to upper esophagus, and is associated with a more frequent
      incidence of multiple reflux events than use of the FM.

PMID- 7726444
TI  - The effects of chewing gum on gastric content prior to induction of general
      anesthesia.
AB  - To study the effects on gastric content and subjective well being of chewing gum
      in the immediate preoperative period, 60 female nonsmokers were randomized to use
      regular, sugar-free chewing gum preoperatively or to continue the overnight fast.
      In a similar fashion 44 habitual smokers were randomized to use nicotine gum 2 mg
      or not. Nonsmokers using chewing gum had significantly larger gastric fluid
      volumes than controls (mean 30 +/- 19 mL vs 20 +/- 15 mL; 95% confidence interval
      (CI) for difference 1-19 mL; P = 0.03), with no difference in gastric fluid
      acidity. In smokers, neither gastric fluid volume nor acidity differed
      significantly between those who were or were not chewing gum. Although the use of
      nicotine gum in smokers was associated with a reduction in dryness of the mouth,
      thirst, and irritability, nonsmokers chewing regular gum did not report
      significant improvements in patient well being. In habitual smokers unable to
      abstain from nicotine, the use of nicotine gum on the morning of surgery may be
      beneficial. Although it is difficult to prove a direct influence on the incidence
      of pulmonary aspiration of increased gastric contents, the fact that regular,
      sugar-free chewing gum increased gastric fluid volumes probably means that it
      should not be used on the morning of surgery.

PMID- 7726445
TI  - Histamine concentrations and hemodynamic responses after remifentanil.
AB  - Remifentanil is a new potent opioid analgesic that undergoes rapid esterase
      metabolism. The purpose of this study was to investigate hemodynamic responses to
      2-30 micrograms/kg remifentanil (escalating doses) injected as a bolus over 1 min
      during general anesthesia. After general anesthesia with endotracheal intubation,
      placement of a radial artery catheter, and pretreatment with glycopyrrolate,
      remifentanil 2, 5, 15, or 30 micrograms/kg (six patients, three male and three
      female per group) was administered over 1 min. Arterial blood pressure and heart
      rate were measured noninvasively before drug administration, after drug
      administration, and then every minute for 5 min. Arterial blood was taken for
      histamine determinations before drug administration and then at 1, 3, and 5 min
      after drug administration. Administration of remifentanil was associated with a
      reduction in systolic blood pressure from 134 +/- 18 to 91 +/- 16 mm Hg and heart
      rate from 99 +/- 20 to 69 +/- 21 bpm and was not associated with alterations in
      histamine concentration.

PMID- 7726446
TI  - Isoflurane-mediated inhibition of the constriction of mesenteric capacitance
      veins and related circulatory responses to acute graded hypoxic hypoxia.
AB  - We measured the effects of inhaled isoflurane on hypoxemia-induced changes in the
      diameter of small mesenteric (capacitance-regulating) veins, sympathetic efferent
      neural activity, heart rate, and arterial blood pressure. Simultaneous changes in
      these dependent variables were measured in situ in response to 40-s periods of
      sequentially administered 10%, 5%, 2.5%, and 0% inspired oxygen before, during,
      and after either 0.75% or 1.5% vol/vol inhaled isoflurane in alpha-chloralose
      anesthetized rabbits. Isoflurane inhibited hypoxia-mediated venoconstriction,
      increases in sympathetic efferent nerve activity, arterial hypertension, and
      bradycardia. Furthermore, inhibition of diameter, blood pressure, and heart rate
      responses persisted after washout of isoflurane. Differences in the attenuation
      of these respective hypoxia-mediated responses were minimal between the two
      concentrations of inhaled isoflurane. These results further demonstrate that
      isoflurane alters the ability to produce cardiovascular adjustments to
      circulatory stress, including changes in vascular capacitance, which is a major
      regulatory mechanism.

PMID- 7726447
TI  - Effect of lipid-lowering treatment on progression of atherosclerotic lesions--a
      duplex ultrasonographic investigation.
AB  - The Prevenzione Aterosclerosi Studio Torino (P.A.S.T.) was a prospective,
      randomized trial testing the effect on carotid and femoral atherosclerotic
      lesions of lipid-lowering therapy, as assessed by duplex scanning (DS) technique,
      in 85 patients (12 women, 73 men), forty-five to fifty-five years old, with
      ischemic heart disease (IHD), and randomly assigned to a hypolipidemic diet or
      diet + 250 mg acipimox (a nicotinic acid compound) two to three times/day. Forty
      one patients, without inclusion criteria, were compared with the randomized
      groups as a reference population. All three groups were submitted to DS and to
      hematic monitoring of lipid levels at the beginning and at the end of the study.
      During three years of treatment, there was a significant reduction (-6.5%) in
      total plasma cholesterol in the diet + drug group (P = 0.04) and a simultaneous
      elevation of high-density lipoprotein cholesterol, significant in the treatment
      groups (respectively, +15% P = 0.02 in the diet and +16% P = 0.016 in the diet +
      drug group). Every group showed a trend toward the increasing number of lesions
      in all explored areas and toward the progression in size of the already existing
      ones. Whereas in the initial DS the prevalence of lesions was significantly lower
      in the nonrandomized group in every site, at the end of the study the total
      number of lesions did not differ among groups, and there was a significant
      increase of plaques in carotid area in the nonrandomized group in comparison with
      the treatment groups. The final number of stable plaques was greater in the
      treatment groups as compared with the nonrandomized group (P = 0.01 diet vs
      nonrandomized, P = 0.03 diet + drug vs nonrandomized). In conclusion, lipid
      lowering treatment, with diet and with diet + drug, was useful in slowing the
      natural progression of atherosclerosis; particularly, it reduced the development
      of new lesions in the carotid and femoral arteries and increased the stability of
      the already existing ones. In these patients, diet was equivalent to diet + drug
      in regard to progression of lesions. The most favorable results in the treatment
      groups seem to correlate with high-density lipoprotein cholesterol, significantly
      increased in comparison with the nonrandomized group.

PMID- 7726448
TI  - Beneficial effects of antioxidants in hemorrhagic shock.
AB  - The present study was undertaken to investigate the role of endogenous hydrogen
      peroxide (H2O2) in cardiac depression and cytotoxicity during hemorrhagic shock
      and reinfusion. To achieve this objective, the changes in the cardiac function
      and contractility, plasma creatine kinase (CK) and CK-MB activity and lactate
      concentration, oxyradical-producing activity of polymorphonuclear leukocytes
      (PMNL-CL), and cardiac malondialdehyde (MDA) concentration in anesthetized dogs
      were determined before and during shock and reinfusion in the presence of absence
      of catalase (a metabolizer of H2O2). The dogs were divided into three groups
      randomly. Group I: sham, four hour duration; group II: two hours of shock
      followed by two hours of reinfusion; group III: same as group II but pretreated
      with catalase. Hemorrhage shock was produced in the dogs by lowering the mean
      arterial pressure to 50 +/- 5 mm Hg by bleeding into standard blood bank bags
      containing 63 mL of citrate, phosphate, dextrose, and adenine (CPDA)
      anticoagulant for 450 mL of blood. The shock was maintained for two hours by
      bleeding or reinfusing the shed blood as needed. Cardiac function and
      contractility were depressed while plasma CK, CK-MB, and lactate increased during
      shock. Reinfusion after two hours of shock tended to return hemodynamic
      parameters and plasma lactate levels toward control values. Plasma CK and CK-MB
      and PMNL-CL increased further. Cardiac MDA content also increased after shock and
      reinfusion, suggesting oxidative damage. Pretreatment with catalase attenuated
      the deleterious effects of shock and reinfusion on the cardiovascular function
      and contractility, and the rise in plasma CK, CK-MB, and lactate, PMNL-CL, and
      cardiac MDA. However, the protection with catalase was not complete. These
      results suggest that hydrogen peroxide (H2O2) may partly be involved in the
      deterioration of cardiovascular function and cellular injury during hemorrhagic
      shock and reinfusion.

PMID- 7726449
TI  - Experimental prosthetic vein valve. Long-term results.
AB  - Chronic venous insufficiency is a disease that carries significant morbidity and
      represents a sizeable burden to the health care system. Current medical and
      surgical therapies are associated with a high incidence of failure. This has
      prompted the development of a synthetic vein valve for the treatment of chronic
      venous insufficiency. Nine dogs underwent the implantation of ten valves into the
      femoral veins. Initial studies showed the valves to be competent and patent.
      However, over a two-year period dense ingrowth of intimal hyperplasia rendered
      the valves functionless.

PMID- 7726450
TI  - Quality assurance of high-dose i.v. heparin treatment exemplified by patients
      implanted with coronary Palmaz-Schatz stents.
AB  - The need to standardize treatment with high-dose IV standard heparin by using
      activated partial thromboplastin time (APTT) reagents tested for their heparin
      sensitivity and by establishing a standard treatment schedule led to the
      development of the "Lainz concept" of heparin management. The determination of
      heparin sensitivity of the 2 APTT reagents used (APTT Micronized Silica and APTT
      Actin FSL), their good agreement (r = .9977; P = .000), and their therapeutic
      APTT ratio of 1.5-2.5 fold of baseline APTT (therapeutic range, forty-five to
      seventy-five seconds) equivalent to 0.3-0.7 antifactor Xa units are presented.
      The "Lainz concept" was tested in 29 patients receiving high-dose heparin after
      coronary artery stenting. A mean dose of 1,273 U of standard heparin/hour (15.7
      U/kg body weight/hour) was shown to produce APTTs in the therapeutic range. From
      the introduction of the "Lainz concept" 81% of the APTTs were kept within the
      therapeutic range by using a defined heparin-monitoring schedule based on a
      guideline protocol for controlling heparin treatment. Only 19% of the APTTs were
      below the therapeutic range. Factors underlying subtherapeutic APTTs are
      discussed. The reduction in the rate of subtherapeutic APTTs to less than 3% seen
      after the introduction of the "Lainz concept" constitutes an important
      contribution toward quality assurance in high-dose heparin treatment.

PMID- 7726451
TI  - Myocardial 18F-FDG-PET. Experiences with the euglycemic hyperinsulinemic clamp
      technique.
AB  - Myocardial positron emission tomography (PET) with 18F-Fluordeoxyglucose (FDG) is
      increasingly used for the detection of viable tissue in the infarcted myocardium.
      Previous studies show that the variable metabolic conditions determine the
      regional distribution of this tracer and that the inhomogeneities of uptake often
      observed even in the normal myocardium may relate to substrate availability. The
      authors tried to stimulate the myocardial FDG uptake by either the technically
      easier method of glucose loading or by the euglycemic hyperinsulinemic clamp
      (EHC) technique. In their hands both methods could be considered as equally
      practicable but differing in some important details in regard to both the study
      protocol (tracer dose, optimal scanning time) and the reproducibility of results.
      The EHC allows a quick stabilization of the metabolic environment and resulted in
      an earlier and markedly increased FDG uptake. However, the important
      standardization of the method was performed by a computer-controlled system only
      for the glucose and insulin infusions. Their experiences show that the EHC
      provides a useful framework for assessing altered cardiac metabolism and possibly
      describes changes after therapeutic interventions more precisely than the
      commonly used glucose-loading technique.

PMID- 7726452
TI  - Safety of echo-dipyridamole test in elderly patients with coronary artery
      disease.
AB  - The authors prospectively studied the feasibility and safety of high-dose
      dipyridamole echocardiography in 166 patients (77 younger and 89 elderly
      patients) referred for clinical evaluation of coronary artery disease.
      Echocardiographic examinations were adequate for analysis of parameters
      considered in 135 of the 166 patients (81.3%; 73 elderly, 62 younger patients).
      The feasibility of dipyridamole echocardiography test was 80.5% in young and 82%
      in elderly patients (P = ns). The incidence of side effects during dipyridamole
      echocardiography was similar in the two groups, except for dyspnea, which was
      observed in 20.5% of older and 3.2% of younger patients (p < 0.05). These data
      demonstrate that the dipyridamole test combined with echocardiographic monitoring
      of regional myocardial contractility may be considered a valid noninvasive method
      of evaluating coronary artery disease in the elderly.

PMID- 7726453
TI  - Multiple cerebral infarcts associated with an atrial septal aneurysm.
      Superimposed thrombus detected by transesophageal echocardiography.
AB  - The authors describe the case of a patient referred for evaluation of
      multiinfarct dementia. Conventional echocardiography revealed an aneurysm of the
      interatrial septum. A transesophageal echocardiogram demonstrated superimposed
      thrombus. This rare cause of systemic emboli can be diagnosed only by
      transesophageal echocardiography and is of major interest to avoid recurrence of
      ischemic strokes.

PMID- 7726454
TI  - Functional lymphatic alterations in patients suffering from lipedema.
AB  - Lipedema is a chronic vascular disease almost exclusively of female sex,
      characterized by the deposit of fat on the legs, with an "Egyptian column" shape,
      orthostatic edema, hypothermia of the skin, alteration of the plantar support,
      and negativity of Stemmer's sign. The etiology and pathogenesis of this disease
      are still the object of study, and therapy is very difficult. Various authors
      have described morphologic and functional alterations of prelymphatic structures
      and of lymphatic vessels. The big veins remain untouched in the phlebograms and
      an alteration of the skin elasticity is demonstrated. The present authors have
      studied by dynamic lymphoscintigraphy 12 women patients suffering from lipedema,
      and compared the results with those of 5 normal subjects and 5 patients suffering
      from idiopathic lymphedema who were sex and age matched with the patients
      suffering from lipedema. The patients suffering from lipedema showed an abnormal
      lymphoscintigraphic pattern with a slowing of the lymphatic flow that presented
      some analogies to the alterations found in the patients suffering from
      lymphedema. A frequent asymmetry was also noticed in the lymphoscintigraphic
      findings that is in contrast to the symmetry of the clinical profile.

PMID- 7726455
TI  - Diagnosis of right pulmonary artery embolism by transesophageal echocardiography.
      A case report.
AB  - The authors report a case of a fifty-one-year-old man undergoing rehabilitation
      therapy following a stroke who suddenly developed right-sided pleuritic chest
      pain with dyspnea. Transesophageal echocardiography was used to demonstrate a
      nonocclusive right pulmonary artery embolus, when other investigative modalities
      failed to establish the diagnosis.

PMID- 7726456
TI  - Successful reduction of endomyocardial fibrosis in a patient with idiopathic
      hypereosinophilic syndrome. A case report.
AB  - A case of endomyocardial fibrosis in a patient with idiopathic hypereosinophilic
      syndrome is reported and discussed. The authors draw attention to the importance
      of both echocardiography (two-dimensional and Doppler) and nuclear magnetic
      resonance in the detection of cardiac involvement due to this rare pathology.
      Moreover, these imaging techniques appear to be valuable in the evaluation of
      effects of medical treatment. Therapy with corticosteroids alone has shown no
      reliable effectiveness in reducing the absolute eosinophil count. A combined
      immunosuppressive treatment with use of hydroxyurea is required.

PMID- 7726457
TI  - Electrocardiographic appearance of a non-Q wave acute myocardial infarction in a
      patient with thyrotoxicosis. A case history.
AB  - A patient with severe thyrotoxicosis developed the typical electrocardiographic
      (ECG) evolution of a non-q myocardial infarction. This occurred without evidence
      of myocardial necrosis and in the absence of coronary artery disease. Treatment
      with beta blockers resolved the ECG changes despite the persistence of the
      thyrotoxic state.

PMID- 7726458
TI  - Two patients with severely displaced maxillary canines respond differently to
      treatment.
AB  - The patient with a severely displaced maxillary canine continues to challenge the
      orthodontic specialist. When the two patients in the following case reports
      presented, their problems seemed similar: each had a palatally displaced canine.
      However, unique clinical problems were soon diagnosed that led to the development
      of different treatment approaches. These differences are worth discussing,
      especially in light of newly published studies. In planning treatment for these
      two patients, the following questions are worth considering. 1. Is it common for
      other dental anomalies (small lateral incisors, missing teeth) to occur more
      frequently in patients with palatally displaced canines? 2. Following surgical
      exposure of palatally displaced maxillary canines, how significant are the risks
      of tooth movement with regard to periodontal health, vitality, and retention? 3.
      Are new or improved surgical procedures becoming available to bring severely
      impacted teeth into alignment? 4. When planning ahead to replace a missing
      premolar with an endosseous implant, is it better to retain the primary molar as
      long as possible or extract it during treatment? 5. How stable is the closure of
      a maxillary median diastema years after a reasonable period of retention?

PMID- 7726459
TI  - Uncovering labially impacted teeth: apically positioned flap and closed-eruption
      techniques.
AB  - The purpose of this study was to examine the esthetic and periodontal differences
      between two methods of uncovering labially impacted maxillary anterior teeth: the
      apically positioned flap and closed-eruption techniques. The sample consisted of
      30 patients who were recalled a minimum of three months after orthodontic
      treatment of a unilateral labially impacted maxillary anterior tooth. Eighteen of
      the patients had undergone an apically positioned flap (APF) procedure, and the
      remaining twelve had undergone the closed-eruption (CE) technique. In the CE
      group, clinical examination showed less width of attached gingiva on the distal
      surface and increased probing bone level on the facial surface of the uncovered
      teeth relative to their contralateral controls. Uncovered teeth in the APF group
      showed more apical gingival margins on the mesial and facial surfaces; greater
      crown length on the midfacial surface; increased probing attachment level on the
      facial surface; increased width of attached gingiva on the facial surface;
      increased probing bone level on mesial, facial, and distal surfaces; and gingival
      scarring. Radiographic examination showed shorter roots on the uncovered teeth in
      both groups. Photographic examination revealed vertical relapse of the uncovered
      teeth in the APF group. We conclude that labially impacted maxillary anterior
      teeth uncovered with an apically positioned flap technique have more unesthetic
      sequalae than those uncovered with a closed-eruption technique.

PMID- 7726460
TI  - Improving orthodontic bonding to silver amalgam.
AB  - Flat rectangular tabs (n = 84) prepared from lathe-cut amalgam (ANA 2000) were
      subjected to aluminum oxide sandblasting or roughening with a diamond bur.
      Mandibular incisor edgewise brackets were bonded to these tabs using: Concise
      (Bis-GMA resin); one of three metal-bonding adhesives, viz., Superbond C&B (4
      META resin), Panavia Ex (10-MDP Bis-GMA resin) or Geristore (composite base); and
      Concise after application of the intermediate resins All-Bond 2 Primers A+B, or
      the Scotch-Bond Multi-Purpose (SBMP) system. All specimens were stored in water
      at 37 degrees C for 24 hours before tensile bond strength testing. Alignment and
      uniform loading during testing were secured by engaging a hook in a circular ring
      soldered onto the bracket slot before bonding. Similar control brackets (n = 12)
      were bonded with Concise to extracted caries-free mandibular incisors. Bond
      failure sites were classified by a modified ARI system. Mean tensile bond
      strengths in the experimental group ranged from 3.4 to 6.4 MPa--significantly
      weaker than the control sample (13.2 MPa). Bond failure generally occurred at the
      amalgam/adhesive interface. Superbond C&B created the strongest bonds to amalgam;
      according to ANOVA and Duncan's Multiple-Range test, they were significantly
      stronger than the bonds with Panavia Ex and Concise, with Geristore in between.
      However, the bond strength of Concise to sandblasted amalgam was comparable to
      the Superbond C&B bonds when coupled with an intermediate application of All-Bond
      2 Primers A+B. The SBMP, on the other hand, was less effective.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7726461
TI  - The CR-CO discrepancy.

PMID- 7726463
TI  - Class II malocclusion: mandibular retrusion or maxillary protrusion?
AB  - This study was undertaken to evaluate whether the majority of Class II skeletal
      patterns are mandibular retrusive or maxillary protrusive and also to compare
      four maxillary sagittal cephalometric indicators and four mandibular sagittal
      cephalometric indicators in a skeletal Class II sample. The Fishman SMA method
      was used to stratify the subjects into 11 maturity levels. Computerized
      cephalometric programs selected the subjects and compared the different
      indicators for each subject. The results indicate a wide diversity in the
      evaluation of maxillary protrusion and mandibular retrusion in these subjects.
      The Downs facial angle indicated that only 27.0% of the sample had mandibular
      retrusion. The angle NA-FH indicates that 56.3% of the sample had maxillary
      protrusion. These findings are in marked contrast to those evaluated by some of
      the other indicators. Preliminary data from this study was presented at a
      combined meeting of the Orthodontic Society of the Cote D'Azur and the North
      Atlantic Component of the E.H. Angle Society of Orthodontists, Nice, France,
      October 1990 and at the annual meeting of the North Atlantic Component of the
      E.H. Angle Society of Orthodontists, Philadelphia, April 1991.

PMID- 7726462
TI  - Stability of the palatal rugae as landmarks for analysis of dental casts.
AB  - The aims of this study were to determine if the palatal rugae are stable during
      normal growth, and whether treatment with either headgear or functional
      appliances affects the position of the rugae. Initial and 15-month recall dental
      casts of 94 patients enrolled in a study of early Class II treatment were
      evaluated. The children had been randomly assigned to one of three groups:
      control (n = 34), headgear (n = 30), and functional appliance (n = 30). Landmarks
      on the palatal raphe and palatal rugae were recorded using the Reflex Metrograph.
      A median palatal plane was constructed using the digitized raphe points as
      reference. Offsets from this plane to the ruga points and transverse and
      anteroposterior linear distances between ruga points were obtained for all casts.
      Transverse offsets and linear distances between medial points of the first rugae
      and the anteroposterior distances between the medial points of the second and
      third rugae did not show statistically significant changes in all groups.
      Significant changes were observed for the lateral points of the rugae,
      particularly in the headgear group. The medial rugae appear to be suitable
      anatomic points for the construction of stable reference planes for longitudinal
      cast analysis.

PMID- 7726464
TI  - Frictional resistances using Teflon-coated ligatures with various bracket
      archwire combinations.
AB  - Static frictional resistances were compared between Teflon-coated stainless steel
      and clear elastomeric ligatures used with various combinations of brackets and
      archwires. Stainless steel metal, polycrystalline ceramic and single crystal
      ceramic 0.022-inch slot brackets were used in combination with stainless steel
      and nickel titanium archwires, 0.018 inch and 0.016 x 0.022 inch. Friction was
      measured in the dry state at bracket-archwire angulations of 0, 5, 10, and 15
      degrees. Moments induced by engagement of the archwires into the brackets were
      measured for each archwire type and bracket-archwire angulation. Teflon-coated
      ligatures produced less friction than elastomers for all bracket-archwire
      combinations. The ceramic brackets generally elicited greater frictional
      resistances than stainless steel brackets. Regarding both friction and control of
      tooth movement, these data suggest that sliding mechanics are best executed with
      stainless steel brackets and stainless steel archwires. Moreover, these data
      reveal the usefulness of Teflon-coated ligatures in minimizing the high friction
      of ceramic brackets when an esthetic appliance is imperative.

PMID- 7726465
TI  - Associated dental anomalies in an Etruscan adolescent.
AB  - Three fragments of the upper jaw of an Etruscan adolescent of the 6th century
      B.C. discovered at the necropolis of Cancellone 1 (Magliano in Tuscany, Grosseto,
      Italy) were examined. A triad of associated dental anomalies was found:
      congenitally missing second premolars, "peg-shaped" permanent lateral incisors,
      and ectopic (palatal) eruption of a permanent canine. These findings provided the
      opportunity to discuss etiopathogenetic aspects of the associations among
      different types of tooth abnormalities.

PMID- 7726466
TI  - Repelling magnets versus super elastic nickel-titanium coils.

PMID- 7726467
TI  - Animal mind and the argument from design.
AB  - The argument from design has played an important role in the history of
      philosophy and biology. Paley, the 19th-century theologian, was struck by the
      bodily complexity and adaptive fit of animals to their environments; he used the
      argument from design to prove the existence of God. Darwin, however, provided the
      natural evolutionary mechanisms that eliminated the need for positing a divine
      creator to explain the structure of animals; he was thus able to treat the
      historical problem of organic evolution by providing a historical solution.
      Today, some students of behavior are similarly struck by the complexity of
      animals' actions and their adaptive fit to the environment. Like Paley, they use
      the argument from design, but to prove the existence of a conscious designer
      inside the head of the animal--the mind. This mentalistic approach suffers from
      many of the philosophical and empirical problems that plagued similar efforts in
      the past.

PMID- 7726468
TI  - Magnitude of psychological gender differences. Another side to the story.
AB  - A. H. Eagly (1995) argued that feminism created a political climate that has lead
      to research that inaccurately minimizes psychological gender differences. In this
      article, the authors assert that feminist psychologists do not have a uniform
      position on this issue, and that many have argued for large gender differences.
      Meta-analyses indicate great variability in the magnitude of gender differences
      across different behaviors. However, more psychological gender differences (25%)
      fall in the close-to-zero range than do other effects in psychology (6%).

PMID- 7726469
TI  - Gender, politics, and psychology's ways of knowing.
AB  - Recent work on the psychology of gender has emphasized comparisons of men and
      women. Such comparisons rest on a view of gender as an individual difference or
      psychological attribute. Feminist theorists have challenged this view as limited
      and inadequate. In place of it, a variety of alternative conceptions of gender
      are emerging. These conceptions shift the focus of analysis from the individual
      to interpersonal and institutional arenas. Moreover, they dispute the idea of
      gender as static, unitary, and separable from other markers of social identity
      and status. In contrast to Alice Eagly (1995), I assert that the production of
      knowledge (whether by scientific procedures or other means) is not set apart from
      society, but rather is always and inevitably embedded within it. Therefore, I
      call for efforts to uncover the ways in which psychological knowledge is shaped
      by ongoing societal struggles and cultural politics.

PMID- 7726470
TI  - Psychological sex differences. Origins through sexual selection.
AB  - Men and women clearly differ in some psychological domains. A. H. Eagly (1995)
      shows that these differences are not artifactual or unstable. Ideally, the next
      scientific step is to develop a cogent explanatory framework for understanding
      why the sexes differ in some psychological domains and not in others and for
      generating accurate predictions about sex differences as yet undiscovered. This
      article offers a brief outline of an explanatory framework for psychological sex
      differences--one that is anchored in the new theoretical paradigm of evolutionary
      psychology. Men and women differ, in this view, in domains in which they have
      faced different adaptive problems over human evolutionary history. In all other
      domains, the sexes are predicted to be psychologically similar. Evolutionary
      psychology jettisons the false dichotomy between biology and environment and
      provides a powerful metatheory of why sex differences exist, where they exist,
      and in what contexts they are expressed (D. M. Buss, 1995).

PMID- 7726471
TI  - Human respiratory tract model for radiological protection. A report of a Task
      Group of the International Commission on Radiological Protection.

PMID- 7726472
TI  - [Perilymph fistula: diagnosis by detection of perilymph in the middle ear by beta
      2 transferrin immunofixation].
AB  - beta 2-transferrin is a specific protein found in the cerebrospinal fluid and in
      the perilymph. Detecting beta 2-transferrin in the middle ear is of great
      interest when a fistula of the perilymph is suspected. This protein can be
      detected on microsamples with an immunofixation technique. We searched for beta 2
      transferrin in pure perilymph, cerebrospinal fluid and serum in 8 patients
      operated by translabyrinthine approach for acoustic tumor removal. Search for
      beta 2-transferrin was performed in liquid from the inner ear in 3
      labyrinthectomies. Samples were taken on collagen sponges or with micro syringes.
      beta 2-transferrin was detected in the perilymph of patients operated for
      neurinoma and in 2 of the 3 labyrinthectomies. This protein was found in only one
      of the patients for which the diagnosis of perilymphatic fistula had been
      retained. Detection of beta 2-transferrin in the middle ear can be proposed as a
      specific diagnostic test for perilymphatic fistula when the clinical situation
      does not suggest a fistula involving cerebrospinal fluid.

PMID- 7726473
TI  - [Clinical and endoscopic aspects of laryngeal dyskinesia in the infant].
AB  - Laryngeal dyskinesia, also called function stridor or stridor by cordal
      dysfunction, has been described in older children and in adults as episodes of
      acute dyspnea sometimes induced by exertion and in a particular psychological
      context. We report 5 cases of infants with stridor due to defective abduction of
      the vocal cords and normal laryngeal opening which occurred at rest or at
      awakening after anaesthesia. The common point was the clinical course of the
      stridor comparable with stridor which occurs during rapid respiration (crying)
      seen at birth then disappearing during the first 18 months of life, and also
      clinically observed gastro-oesophageal reflux which was confirmed by oesophageal
      pH measurements. Two infants had malaise with vagal hyperactivity. Disappearance
      of the stridor had no times relationship with the initiation of anti-reflux
      treatment and disappeared progressively near the end of the first year of life.

PMID- 7726474
TI  - [Hypoparathyroidism after thyroid surgery].
AB  - The authors report their experience of hypoparathyroidism in thyroid surgery: 538
      patients underwent thyroidectomy, including 45% bilateral resections. In post
      operative period, accurate tests allowed to detect non permanent hypocalcemias in
      60% of cases. Severe hypocalcemia (1.60 mmol/l) is necessary to engage a
      treatment by vitamin D. So, a soft thyroid microsurgery is the only one manner to
      preserve parathyroid stock. 46 patients had parathyroid transplantation, but the
      evaluation is difficult, because the amount of parathyroid gland without
      ischemia, left into the neck, is unknown. In summary, this technique is
      effective, but often useless in thyroid surgery.

PMID- 7726475
TI  - [Value of ultrasonography in the detection of metastatic cervical lymph nodes].
AB  - A prospective study of 18 consecutive patients with carcinoma of upper
      respiratory and digestive tracts is presented. The authors describe the lymph
      node involvement in these cases. Preoperative ultrasound exploration of the
      cervical node regions was performed and US findings were compared with obtain by
      physical examination. Despite the limitations of ultrasonography, the diagnostic
      and prognostic interest were emphasized. Associated with color doppler, higher
      specificity and sensibility were noted.

PMID- 7726476
TI  - [Current aspects of laryngeal tuberculosis. Apropos of 4 cases and review of the
      literature].
AB  - After the discovery of streptomycin 1944, laryngeal tuberculosis became a rare
      complication of advanced pulmonary tuberculosis. Since that time the clinical
      aspects of the disease have changed. We analyzed these changes by reviewing 65
      papers in English and in French published from 1965 to 1991 involving 738 cases
      and added our 4 new personal cases. To our knowledge, we report the first two
      well-documented cases of laryngeal tuberculosis in HIV positive patients. We
      propose a therapeutic and follow-up protocol for laryngeal and chest specialists
      treating such patients.

PMID- 7726477
TI  - [Value of coral implant in the treatment of functional failure after subtotal
      laryngectomy with crico-hyoid fixation].
AB  - Subtotal laryngectomy with CHP have prolongated post operative care because
      aspiration. In 16% of cases a new surgical procedure is necessary. The authors
      have used a implant of madreporic coral placed in the base of the tongue just
      behind the hyoid bone to achieve a total closure of the larynx during swallowing.
      This operation has stopped aspiration in 2 cases very quickly.

PMID- 7726478
TI  - [Surgical approach of the petrous vertical segment and upper cervical internal
      carotid].
AB  - The main obstacle to successful management of aneurysms involving the high
      cervical internal carotid artery (ICA) is to obtain an adequate exposure. In this
      report we describe our experience in 5 patients presenting carotid aneurysms at
      the skull base, intermediately below the carotid foramen. Exposure is achieved in
      two stages. The cervical stage consists in resection of the styloid processes and
      muscles followed by anterior displacement of the mandibular condyle. This exposes
      the vertical segment of the petrous ICA. The petrous stage consists in partial
      petrectomy exposing the jugular bulb and the third segment of the facial nerve.
      Using this route, the vertical intrapetrous segment of the ICA can be drilled
      away without damaging the middle ear. In our series, no vascular complications
      occurred. Damage involving the facial glossopharyngeal and vagal nerves is
      discussed. This approach appears to be a suitable alternative to the conventional
      infratemporal approach which sacrifices the middle ear.

PMID- 7726479
TI  - [Efficacy and tolerance of cefotiam hexetil in the super-infected chronic
      sinusitis. A randomized, double-blind study in comparison with cefixime].
AB  - Efficacy and safety of a new oral third generation Cephalosporin, Cefotiam
      Hexetil (CTM) 200 mg bid were compared with those of Cefixime (CX) 200 mg bid
      over 10 day duration of treatment. One hundred and twenty two ambulatory adults
      suffering from chronic sinusitis were randomized by ENT specialists in this
      multicentre prospective double blind, doubled dummy study. Sinusitis diagnosis
      evocated in front of fascial pain, purulent nasal discharge and/or obstruction
      was confirmed with sinus X-ray. Use of antibiotics or corticosteroids
      concomitantly or 15 days prior inclusion represented one of the major exclusion
      criterion. One hundred and seventy one patients were evaluated for efficacy
      analysis (62 and 59 respectively in CTM and CX groups). Regarding demographic
      data, clinical and radiological signs, the two populations were comparable at
      inclusion excepted for sex and weight (female: 73% in CTM group versus 47% in CX
      group). The overall clinical success rate at the end of treatment
      (cure+improvement) was not significantly different between the two groups (CTM:
      82% versus CX: 80%). The incidence of adverse events was less frequent in the CTM
      group (14.5% versus 19%). In conclusion, CTM 200 mg bid is as efficacious and as
      well tolerated as CX 200 mg bid in the treatment of chronic sinusitis in adults.

PMID- 7726480
TI  - [Small-cell carcinoma of the parotid gland. Apropos of a case].
AB  - One case of primary small cell carcinoma of the left parotid gland is reported. A
      total parotidectomy with facial nerve preservation and left functional neck
      dissection was performed, with postoperative radiotherapy to the surgical area. A
      lymph node metastases appears 4 months later, and it needs radical neck
      dissection followed by chemotherapy. 18 months following initial surgery, our
      patient is free of disease. The ultrastructural and immunohistochemical studies
      does not suggest an origin neuroendocrine of the carcinoma. This tumor appears to
      have a better prognosis than small cell carcinoma of the lung, which it resembles
      histologically.

PMID- 7726481
TI  - [Blue rubber bleb naevus syndrome. Diagnosis and management apropos of 2 cases].
AB  - Blue Rubber Bleb Naevus Syndrome is a rare pathology: 70 cases have been noted
      since the first description, by Gascoyen, in 1860. It is an acquired disease
      which usually appears before the age of ten. It is marked by angiomatic cutaneo
      digestive tumours combined with chronic anaemia and iron deficiency. Its many and
      various complications, particularly cataclysmic haemorrhages, car jeopardize the
      vital prognosis throughout. This little known syndrome is rarely diagnosed at the
      time of its first manifestations. We recall, from two cases and a review of their
      literature, the clinical characteristics of the syndrome, its complications and
      its essentially symptomatic treatment. We therefore suggest an approach to its
      diagnosis.

PMID- 7726482
TI  - [ORL surgery in Albucasis's treatise on surgery. A vision of cervicofacial
      surgical therapeutics in the year 1000].
AB  - The work of the famous Arab doctor, Albucasis, is not well known to head and neck
      surgeons. However, the thirtieth time of his treatise on medicine is essentially
      a surgical textbook and includes many. Facts concerning otorhinolaryngology.
      Albucasis's complete work is an exhaustive compilation of late tenth century
      medical knowhow which ensured the link between ancient medicine, essentially of
      Greek origin, and modern western medicine. The important work of Jewish and Arab
      physicians in the early and late Middle Ages was necessary for the transmission
      of knowledge from the ancient near last to the modern western world. Among
      Albucasis's descriptions of surgical techniques, tonsillectomy and trachestomy
      are particularly interesting. In order to accurately formulate indications for
      surgery, Albucasis endeavors to present the signs and symptoms of pathological
      conditions requiring surgical treatment. Finally, Albucasis reveals himself to be
      a humanist, as well as a physician and surgeon.

PMID- 7726484
TI  - Intranasal pirodavir (R77,975) treatment of rhinovirus colds.
AB  - A randomized, double-blind, placebo-controlled trial assessed the therapeutic
      efficacy of intranasal pirodavir in naturally occurring rhinovirus colds. Adults
      with symptoms of < or = 2 days' duration were randomly assigned to intranasal
      sprays of pirodavir (2 mg per treatment) or placebo six times daily for 5 days.
      In people with laboratory-documented rhinovirus colds (53 in the pirodavir group,
      55 in the placebo group), no significant differences in the resolution of
      respiratory symptoms were apparent between the groups. The median duration of
      illness was 7 days in each group. Similarly, scores for individual symptoms found
      no differences in favor of pirodavir during or after treatment. In contrast,
      reduced frequencies of rhinovirus shedding were observed in the pirodavir group
      on day 3 (70 versus 23%; P < 0.001) and day 5 (38 versus 12%; P = 0.002) but not
      after the cessation of treatment, on day 7 (19 versus 21%). No pirodavir
      resistant viruses were recovered from treated individuals. The pirodavir group
      had higher rates of nasal dryness, blood in mucus, or unpleasant taste on several
      study days. In summary, intranasal sprays of pirodavir were associated with
      significant antiviral effects but no clinical benefit in treating naturally
      occurring rhinovirus colds.

PMID- 7726485
TI  - In vitro antifungal and fungicidal spectra of a new pradimicin derivative, BMS
      181184.
AB  - A new pradimicin derivative, BMS-181184, was compared with amphotericin B and
      fluconazole against 249 strains from 35 fungal species to determine its
      antifungal spectrum. Antifungal testing was performed by the broth macrodilution
      reference method recommended by the National Committee for Clinical Laboratory
      Standards (document M27-P, 1992). BMS-181184 MICs for 97% of the 167 strains of
      Candida spp., Cryptococcus neoformans, Torulopsis glabrata, and Rhodotorula spp.
      tested were < or = 8 micrograms/ml, with a majority of MICs being 2 to 8
      micrograms/ml. Similarly, for Aspergillus fumigatus and 89% of the 26
      dermatophytes tested BMS-181184 MICs were < or = 8 micrograms/ml. BMS-181184 was
      fungicidal for the yeasts, dermatophytes, and most strains of A. fumigatus,
      although the reduction in cell counts was less for A. fumigatus than for the
      yeasts. BMS-181184 was active against Sporothrix schenckii, dematiaceous fungi,
      and some members of the non-Aspergillus hyaline hyphomycetes. BMS-181184,
      however, was not fungicidal against members of the family Dematiaceae. BMS-181184
      lacked activity or had poorer activity (MICs, > or = 16 micrograms/ml) against
      Aspergillus niger, Aspergillus flavus, Malassezia furfur, Fusarium spp.,
      Pseudallescheria boydii, Alternaria spp., Curvularia spp., Exserohilum
      mcginnisii, and the zygomycetes than against yeasts. The activity of BMS-181184
      was minimally (twofold or less) affected by changes in testing conditions (pH,
      inoculum size, temperature, the presence of serum), testing methods (agar versus
      broth macrodilution), or test media (RPMI 1640, yeast morphology agar, high
      resolution test medium). Overall, our results indicate that BMS-181184 has a
      broad antifungal spectrum and that it is fungicidal to yeasts and, to a lesser
      extent, to filamentous fungi.

PMID- 7726486
TI  - Antimicrobial activities of amphiphilic peptides covalently bonded to a water
      insoluble resin.
AB  - A series of polymer-bound antimicrobial peptides was prepared, and the peptides
      were tested for their antimicrobial activities. The immobilized peptides were
      prepared by a strategy that used solid-phase peptide synthesis that linked the
      carboxy-terminal amino acid with an ethylenediamine-modified polyamide resin
      (PepsynK). The acid-stable, permanent amide bond between the support and the
      nascent peptide renders the peptide resistant to cleavage from the support during
      the final acid-catalyzed deprotection step in the synthesis. Select immobilized
      peptides containing amino acid sequences that ranged from the naturally occurring
      magainin to simpler synthetic sequences with idealized secondary structures were
      excellent antimicrobial agents against several organisms. The immobilized
      peptides typically reduced the number of viable cells by > or = 5 log units. We
      show that the reduction in cell numbers cannot be explained by the action of a
      soluble component. We observed no leached or hydrolyzed peptide from the resin,
      nor did we observe any antimicrobial activity in soluble extracts from the
      immobilized peptide. The immobilized peptides were washed and reused for repeated
      microbial contact and killing. These results suggest that the surface actions by
      magainins and structurally related antimicrobial peptides are sufficient for
      their lethal activities.

PMID- 7726483
TI  - Trimethoprim and sulfonamide resistance.

PMID- 7726487
TI  - Development of test panel of beta-lactamases expressed in a common Escherichia
      coli host background for evaluation of new beta-lactam antibiotics.
AB  - A test panel of 35 different beta-lactamases expressed in a common Escherichia
      coli host was created to compare the effect that each beta-lactamase had on
      susceptibility to various beta-lactam antibiotics. A comparison of the MICs
      obtained with this panel generally reflected differences in the substrate
      profiles of the various beta-lactamases examined. In addition, several strains of
      the panel were subjected to selection with porin-specific bacteriophages to
      obtain mutants lacking either the OmpC or OmpF porin protein. A mutation in
      either OmpC or OmpF did change the susceptibilities of certain strains expressing
      beta-lactamase to certain beta-lactam antibiotics. However, the loss of a single
      porin did not predictably alter susceptibility to any given beta-lactam drug.
      This panel of strains producing various beta-lactamases was found to be a useful
      tool for comparing the effects of different beta-lactamases and outer membrane
      permeability upon susceptibility to beta-lactam drugs.

PMID- 7726488
TI  - Comparative and collaborative evaluation of standardization of antifungal
      susceptibility testing for filamentous fungi.
AB  - The purpose of the study was to evaluate the interlaboratory agreement of broth
      dilution susceptibility methods for five species of conidium-forming (size range,
      2 to 7 microns) filamentous fungi. The methods used included both macro- and
      microdilution methods that were adaptations of the proposed reference method of
      the National Committee for Clinical Laboratory Standards for yeasts (m27-P). The
      MICs of amphotericin B, fluconazole, itraconazole, miconazole, and ketoconazole
      were determined in six centers by both macro- and microdilution tests for 25
      isolates of Aspergillus flavus, Aspergillus fumigatus, Pseudallescheria boydii,
      Rhizopus arrhizus, and Sporothrix schenckii. All isolates produced clearly
      detectable growth within 1 to 4 days at 35 degrees C in the RPMI 1640 medium.
      Colony counts of 0.4 x 10(6) to 3.3 x 10(6) CFU/ml (mean, 1.4 x 10(6) CFU/ml)
      were demonstrated in 90% of the 148 inoculum preparations. Overall, good
      intralaboratory agreement was demonstrated with amphotericin B, fluconazole, and
      ketoconazole MICs (90 to 97%). The agreement was lower with itraconazole MICs (59
      to 79% median). Interlaboratory reproducibility demonstrated similar results: 90
      to 100% agreement with amphotericin B, fluconazole, miconazole, and ketoconazole
      MICs and 59 to 91% with itraconazole MICs. Among the species tested, the MICs for
      S. schenckii showed the highest variability. The results of the study imply that
      it may be possible to develop a reference method for antifungal susceptibility
      testing of filamentous fungi.

PMID- 7726489
TI  - Inhibition of human immunodeficiency virus integrase by bis-catechols.
AB  - The human immunodeficiency virus type 1 (HIV-1) integrase protein is required for
      the productive infection of T-lymphoid cells in culture (R. L. LaFemina, C. L.
      Schneider, H. L. Robbins, P. L. Callahan, K. LeGrow, E. Roth, W. A. Schleif, and
      E. A. Emini, J. Virol. 66:7414-7419, 1992). This observation suggests that
      chemical inhibitors of integrase may prevent the spread of HIV in infected
      individuals. In our search for such potential chemotherapeutic agents, we
      observed that beta-conidendrol inhibits both the sequence-dependent and sequence
      independent endonucleolytic activities of integrase with comparable potencies in
      vitro (50% inhibitory concentration, 500 nM). Structurally related compounds
      tested for their abilities to inhibit integrase generated a limited structure
      activity analysis which demonstrated that potency is associated with the bis
      catechol structure: two pairs of adjacent hydroxyls on separate benzene rings.
      beta-Conidendrol did not inhibit several other endonucleases and/or
      phosphoryltransferases. Although beta-conidendrol was not effective in preventing
      HIV-1 infection in cell culture, the in vitro data demonstrate that it is
      possible to identify selective agents targeted against this essential HIV-1
      function.

PMID- 7726491
TI  - Influence of pulmonary surfactant on in vitro bactericidal activities of
      amoxicillin, ceftazidime, and tobramycin.
AB  - The influence of a natural pulmonary surfactant on antibiotic activity was
      investigated to assess the possible use of exogenous surfactant as a vehicle for
      antibiotic delivery to the lung. The influence of surfactant on the bactericidal
      activity of amoxicillin was tested against Staphylococcus aureus and
      Streptococcus pneumoniae, and the influence of surfactant on the activities of
      ceftazidime and tobramycin was tested against Klebsiella pneumoniae, Pseudomonas
      aeruginosa, S. aureus, and S. pneumoniae. In vitro antibiotic activity was
      determined by killing curve studies in media with and without surfactant.
      Amoxicillin and ceftazidime activities were not changed in the presence of
      surfactant, except for a decreased killing rate of S. pneumoniae by ceftazidime
      in medium with additional rabbit serum. In contrast, killing curves with low
      concentrations of tobramycin (0.25x and 1x the MIC) showed a decreased level of
      activity of tobramycin against all pathogens tested in the presence of
      surfactant. With higher tobramycin concentrations (4x the MIC) killing rates were
      decreased less or were unchanged in the presence of surfactant. Concluding from
      the results of the study, both amoxicillin and ceftazidime can be combined with
      surfactant without the loss of activity. For mixing surfactant with tobramycin,
      dosages should be adjusted to overcome the partial inactivation of tobramycin by
      surfactant.

PMID- 7726490
TI  - Effects of atovaquone and other inhibitors on Pneumocystis carinii dihydroorotate
      dehydrogenase.
AB  - Dihydroorotate dehydrogenase (DHOD) is a pyrimidine biosynthetic enzyme which is
      usually directly linked to the mitochondrial respiratory chain. Antimalarial
      naphthoquinones such as atovaquone (566c80) inhibit malarial DHOD by inhibiting
      electron transport. Since atovaquone also has therapeutic activity against
      Pneumocystis carinii, the P. carinii DHOD may also be an important drug target.
      Organisms were obtained from immunosuppressed rats, incubated for 24 h in a short
      term in vitro culture system, and then lysed. P. carinii lysates catalyzed the
      generation of orotate from dihydroorotate at a rate of 852 pmol/mg of protein per
      min. Control preparations made from uninfected mice showed much less total
      enzymatic activity and enzyme specific activity. As expected, P. carinii DHOD
      activity was susceptible to respiratory inhibitors such as cyanide, antimycin A,
      and salicylhydroxamic acid (SHAM). Susceptibility to SHAM suggests the presence
      of an alternative oxidase. In contrast, neither pentamidine nor 5-hydroxy-6
      demethylprimaquine (5H6DP), a quinone metabolite of primaquine, inhibited the
      enzyme. Atovaquone inhibited DHOD by 76.3% at 100 microM and 36.5% at 10 microM.
      A similar degree of inhibition was found when the organisms were preincubated
      with the drug. Atovaquone inhibited P. carinii growth in vitro at a somewhat
      lower concentration (between 0.3 and 3 microM). In contrast, Plasmodium
      falciparum growth and enzyme activity are susceptible to nanomolar concentrations
      of atovaquone. Thus, while it is possible that atovaquone acts by inhibiting the
      P. carinii electron transport chain, the possibility of another drug target
      cannot be excluded.

PMID- 7726492
TI  - Intrapulmonary pharmacokinetics of clarithromycin and of erythromycin.
AB  - The intrapulmonary pharmacokinetics of orally administered clarithromycin (500 mg
      every 12 h for five doses) or erythromycin (250 mg every 6 h for nine doses) were
      studied in 32 healthy adult volunteers. Four of the subjects, two in the
      clarithromycin group and two in the erythromycin group, were smokers.
      Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed at 4, 8,
      12, 24, and 48 h after administration of the last dose of clarithromycin and at
      4, 8, and 12 h after administration of the last dose of erythromycin.
      Clarithromycin was measured by high-performance liquid chromatography, and
      erythromycin was measured by a microbiological assay. No systemic sedation was
      used. There were no major adverse events. The concentrations of antibiotics in
      epithelial lining fluid (ELF) were calculated by the urea dilution method. The
      volumes (mean +/- standard deviation) of ELF were 1.9 +/- 2.0 ml and 1.5 +/- 0.7
      ml in the clarithromycin and erythromycin groups, respectively (P > 0.05). There
      was no effect of smoking on the amount of bronchoalveolar lavage fluid recovered,
      the volume of ELF, or the number of erythrocytes present in the lavage fluid (P >
      0.05 for all comparisons). The total number of alveolar cells, however, was
      almost threefold greater in the smokers versus that in the nonsmokers (P < 0.05).
      Clarithromycin was concentrated in ELF (range, 72.1 +/- 73.0 micrograms/ml at 8 h
      to 11.9 +/- 3.6 micrograms/ml at 24 h) and alveolar cells (range, 505.8 +/- 293.1
      micrograms/ml at 4 h to 17.0 +/- 34.0 micrograms/ml at 48 h). 14-(R)
      Hydroxyclarithromycin was also present in these compartments, but at lower
      concentrations than the parent compound. The concentrations of erythromycin in
      ELF and alveolar cells were low at 4, 8, and 12 h following the last dose of drug
      (range, 0 to 0.8 +/- microgram/ml in ELF and 0 to 0.8 +/- 1.3 microgram/ml in
      alveolar cells). The clinical significance of any antibiotic concentrations in
      these compartments in unclear. The data suggest, and we conclude, that
      clarithromycin may be a useful drug in the treatment of pulmonary infections,
      particularly those caused by intracellular organisms.

PMID- 7726493
TI  - Amoebicidal efficiencies of various diamidines against two strains of
      Acanthamoeba polyphaga.
AB  - The first medical cure of Acanthamoeba keratitis was obtained by use of
      propamidine isethionate. Since then, it has been the basic drug recommended for
      use in treatment. Because some Acanthamoeba strains have been reported to be
      resistant to propamidine and propamidine was found to be only weakly cysticidal,
      superior homologs such as butamidine, pentamidine, hexamidine, heptamidine,
      octamidine, and nonamidine were tested for their amoebicidal effects on two
      Acanthamoeba strains isolated from patients with keratitis. Trophozoicidal and
      cysticidal efficiencies were found to be increased from propamidine to
      nonamidine; i.e., when the alkyl chain connecting the two benzene rings in their
      molecular structures was elongated, in comparison with propamidine, hexamidine
      and octamidine were the most amoebicidal molecules. As a result of these data, a
      kinetic study carried out on propamidine, hexamidine, and octamidine demonstrated
      that the amoebicidal effects resulted from two events: the diffusion of molecules
      through the plasma membrane or the double wall of trophozoites or cysts,
      respectively, and the lethal effects of molecules on amoebic protoplasm. The
      diffusion kinetics were increased when the alkyl chain was elongated, i.e., with
      an increase in the lipophilic properties of molecules. In contrast, the lethal
      effect kinetics were found to be unchanged by this elongation, indicating that
      they originated from the cationic surface-active properties induced by the
      protonated amidine groups attached to each benzene ring, which themselves
      remained unchanged from one molecule to the other. These results strongly
      advocate the immediate replacement of propamidine by hexamidine in the medical
      treatment of Acanthamoeba keratitis; in France, 0.1% hexamidine eyedrops are
      available (Desomedine). The results also advocate clinical investigations on the
      efficiency and toxicity of octamidine, which appears to be the most amoebicidal
      diamidine in vitro.

PMID- 7726494
TI  - Effect of zidovudine on transplacental pharmacokinetics of ddI in the pigtailed
      macaque (Macaca nemestrina).
AB  - Since zidovudine and ddI may be used in combination in the future to treat
      pregnant women who are human immunodeficiency virus positive, we conducted a
      study to determine whether zidovudine affects the transfer of ddI across the
      placenta. Zidovudine and ddI were infused simultaneously to three near-term
      pregnant macaques (Macaca nemestrina) at 156 +/- 1.5 days of gestation. Samples
      of maternal and fetal blood and amniotic fluid were drawn at intervals for 30 h.
      The steady-state dideoxyinosine concentrations in the plasma of the dam (Cssd),
      the fetus (Cssf), and the amniotic fluid (Cssa) and the ratios Cssf/Cssd and
      Cssa/Cssf were found to be not significantly different from the values previously
      determined after the administration of ddI alone during the same pregnancy. We
      conclude that concurrent zidovudine administration does not affect the transfer
      of ddI across the placenta in near-term Macaca nemestrina.

PMID- 7726495
TI  - Distribution of cphA or related carbapenemase-encoding genes and production of
      carbapenemase activity in members of the genus Aeromonas.
AB  - The prevalence of the cphA gene or related carbapenemase-encoding genes was
      investigated in 114 Aeromonas strains belonging to the six species of major
      clinical interest. A species-related distribution of cphA-related sequences was
      observed. Similar sequences were found in A. hydrophila, A. veronii bv. sobria,
      A. veronii bv. veronii, and A. jandaei, but not in A. caviae, A. trota, or A.
      schubertii. However, a single A. caviae strain (of 62 tested) was found carrying
      cphA-related sequences, suggesting the possibility of the horizontal transfer of
      this gene to species which normally do not carry it. Production of carbapenemase
      activity was detectable in 83% of the hybridization-positive strains but in none
      of the hybridization-negative ones. When it was present, carbapenemase activity
      was always inhibitable by EDTA. Either carbapenemase-producing or not, Aeromonas
      strains appeared to be susceptible to imipenem when in vitro susceptibility
      testing was performed with inocula of conventional size (10(5) CFU), for which
      MICs were always < or = 1 microgram/ml. With a larger inoculum (10(8) CFU), the
      MICs for carbapenemase-negative strains always remained < or = 1 microgram/ml,
      while those for carbapenemase-producing strains were always > or = 4
      micrograms/ml, being usually higher than the breakpoint for susceptibility. The
      present results indicate that the production of metallocarbapenemase activity,
      apparently encoded by cphA homologs, is widespread among some of the Aeromonas
      species of clinical interest (A. hydrophila, A. veronii bv. sobria, A. veronii
      bv. veronii, and A. jandaei) and that imipenem MICs for carbapenemase-producing
      strains are subjected to a relevant inoculum size effect.

PMID- 7726496
TI  - Relative importances of outer membrane permeability and group 1 beta-lactamase as
      determinants of meropenem and imipenem activities against Enterobacter cloacae.
AB  - The roles of outer membrane permeability and Bush group 1 beta-lactamase activity
      in determining Enterobacter cloacae susceptibility to either meropenem or
      imipenem were investigated. A beta-lactamase-deficient strain was obtained by
      mutagenesis from a clinical isolate of E. cloacae, and a porin-deficient strain
      was selected from this mutant with cefoxitin. Both strains were transformed with
      the plasmid pAA20R, which contained the gene coding for the carbapenem
      hydrolyzing CphA beta-lactamase, and the carbapenem permeability coefficients
      were measured by the Zimmermann and Rosselet technique (W. Zimmermann and A.
      Rosselet, Antimicrob. Agents Chemother. 12:368-372, 1977). The permeability
      coefficient of meropenem was roughly half that of imipenem in the normally
      permeable strain and almost seven times lower than that of imipenem in the porin
      deficient strain. In the porin-deficient strain, the virtual absence of porins
      caused the MICs of meropenem to increase from 8 to 16 times, while it did not
      affect the MICs of imipenem. Conversely, the beta-lactamase affected imipenem but
      not meropenem activity: meropenem showed a similar activity in the parent strain
      and in the beta-lactamase-deficient mutant with both a low- and high-density
      inoculum, whereas imipenem was 16 times less active against the parent strain
      when the high-density inoculum was used. It is concluded that outer membrane
      permeability and stability to group 1 beta-lactamase have different impacts on
      the activities of meropenem and imipenem against E. cloacae.

PMID- 7726497
TI  - Multiple-dose pharmacokinetics of ceftibuten in healthy volunteers.
AB  - The pharmacokinetics of ceftibuten, a new cephalosporin antibiotic, and its
      conversion product, ceftibutentrans, were studied in healthy male volunteers
      following daily oral administration of a 400-mg capsule for 7 days. Mean
      concentrations of ceftibuten in plasma obtained on day 5 were similar to those
      obtained on day 7. Analysis of variance indicated that the concentrations in
      plasma on days 5 and 7 were at steady state. The mean accumulation factor was
      1.14 for day 5 and 1.13 for day 7. The half-life (2.4 h) was independent of the
      duration of drug administration, and the mean maximum concentration of drug in
      plasma was 18 to 19 micrograms/ml. Urinary excretion was the major elimination
      route for ceftibuten, by which 57 to 59% of the drug was excreted unchanged over
      a 24-h period. The amounts of ceftibuten-trans in plasma and urine were low.

PMID- 7726498
TI  - Pharmacokinetics and dose proportionality of ceftibuten in men.
AB  - The pharmacokinetics and dose proportionality of ceftibuten were evaluated in
      healthy male volunteers receiving single oral doses of 200, 400, and 800 mg of
      ceftibuten. The drug was absorbed with similar times to the maximum concentration
      of drug in plasma for all three doses. Concentrations of ceftibuten in plasma
      increased with increasing dose. Analysis of variance was carried out on the dose
      adjusted values for the maximum concentration of drug in plasma and the area
      under the plasma concentration-time curve; the results indicated that the
      concentrations in plasma after the 200- and 400-mg doses were dose proportional,
      and after the 800-mg of dose they were less than dose proportional. The
      elimination half-life from plasma ranged from 2.0 to 2.3 h and was independent of
      dose. The total excretion of unchanged ceftibuten in urine accounted for 53 to
      68% of the dose, and the renal clearance was estimated to be 53 to 61 ml/min
      after all doses. The amount of ceftibuten-trans, the major in vitro and in vivo
      conversion product of ceftibuten, was low in both plasma and urine.

PMID- 7726499
TI  - Heterogeneity of the vanA gene cluster in clinical isolates of enterococci from
      the northeastern United States.
AB  - In several strains of Enterococcus faecium isolated in Europe, the cluster of
      genes encoding high-level resistance to vancomycin (VanA phenotype) resides on a
      10.85-kb transposon, Tn1546, or closely related elements. To determine whether
      Tn1546 was conserved in recent enterococcal isolates from the northeastern United
      States, seven strains were compared by restriction mapping and DNA hybridization
      with probes from within the van cluster. Two of the seven strains contained
      intact Tn1546-like sequences; however, in five of the strains, the organization
      of the van cluster differed from that of Tn1546. Three of the five strains with
      variations harbored a novel DNA segment within the van gene cluster. This 1,496
      bp segment was similar to IS1165 of Leuconostoc mesenteroides and IS1181 of
      Staphylococcus aureus and was flanked by 24- and 23-bp imperfect inverted repeats
      and 8-bp direct repeats. On the basis of these findings, we propose that this
      element comprises a novel insertion-like sequence, IS1251. Multiple copies of
      IS1251 were also present at other sites in both resistant and susceptible
      clinical isolates. Our findings suggest that the van cluster in recent isolates
      from the northeastern United States differs from that present in the early
      European VanA phenotype strains.

PMID- 7726500
TI  - Prevalence of erm gene classes in erythromycin-resistant Staphylococcus aureus
      strains isolated between 1959 and 1988.
AB  - The epidemiology of the two common erythromycin resistance methylase (erm) genes
      ermA and ermC was analyzed by Southern blotting in 428 erythromycin-resistant
      Staphylococcus aureus strains isolated from blood between 1959 and 1988 in
      Denmark. ermA and/or ermC was present in 98% of the erythromycin-resistant
      strains tested. ermA was found only as a chromosomal insert and was solely
      responsible for erythromycin resistance in these strains until about 1971. ermA
      was the only erm gene found in 337 strains and was a single insert in 61% of
      these strains, two inserts were seen in 37%, and three inserts were found in 2%.
      Thirteen different ermA EcoRI restriction fragment length polymorphisms were
      identified. ermA was not found in strains of phage type patterns group II and
      type 95, which are very common today. ermC was found on a plasmid in 77 strains.
      ermC was first seen in 1971 and spread rapidly in the S. aureus population, with
      a 5- to 10-fold increase every 5 years, and in 1984 to 1988, it was responsible
      for erythromycin resistance in 72% of the strains. The predominant plasmid
      carrying ermC was 2.5 kb, while four plasmids were smaller and three were larger.
      ermC has been found in all phage type patterns. Eight strains contained
      combinations of ermA and ermC, and no erm gene was detected in six strains.

PMID- 7726502
TI  - In vitro activity of BMS-181139, a new carbapenem with potent antipseudomonal
      activity.
AB  - The in vitro activities of the carbapenem BMS-181139 were determined in
      comparison with those of imipenem, meropenem, ciprofloxacin, ceftriaxone, and
      vancomycin. BMS-181139 was the most active against species of Pseudomonas and
      related genera Alteromonas and Burkholderia, with MICs for 147 of 149 isolates of
      < 4 micrograms/ml. Of 22 imipenem-resistant (MIC > 8 micrograms/ml) P. aeruginosa
      strains, only 1 required an MIC of BMS-181139 of > 4 micrograms/ml, compared with
      14 requiring the same meropenem MIC. BMS-181139 was the most active carbapenem
      against the majority of other gram-negative species except members of the tribe
      Proteeae, against which meropenem was more active. Although imipenem was more
      active against gram-positive species, BMS-18139 MICs at which 90% of strain
      tested were inhibited were < 1 microgram/ml for these species. BMS-181139 was
      generally active against isolates resistant to ciprofloxacin or broad-spectrum
      cephalosporins, including those containing plasmid-encoded beta-lactamases or
      high levels of chromosome-encoded beta-lactamases, as well as anaerobes except
      Clostridium difficile. Inoculum effects were noted for all three carbapenems
      against Klebsiella pneumoniae, Enterobacter cloacae, and Serratia marcescens but
      not Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus. BMS
      181139's inoculum effect tended to be more marked. BMS-181139 exhibited
      bactericidal activity at the MIC for some strains and up to four to eight times
      the MIC for others. The postantibiotic effect of BMS-181139 was equal to or less
      than that of imipenem and, like meropenem, exhibited intraspecies variability.
      BMS-181139 was 30-fold more stable than imipenem and 7-fold more stable than
      meropenem to hydrolysis by hog kidney dehydropeptidase.

PMID- 7726501
TI  - Antiviral properties of aminodiol inhibitors against human immunodeficiency virus
      and protease.
AB  - A series of aminodiol inhibitors of human immunodeficiency virus type 1 (HIV-1)
      protease were identified by using an in vitro peptide cleavage assay. BMS
      182,193, BMS 186,318, and BMS 187,071 protected cells against HIV-1, HIV-2, and
      simian immunodeficiency virus infections, with 50% effective doses ranging from
      0.05 to 0.33 microM, while having no inhibitory effect on cells infected with
      unrelated viruses. These compounds were also effective in inhibiting p24
      production in peripheral blood mononuclear cells infected with HIV-1 IIIB and
      against the zidovudine-resistant HIV-1 strain A018C. Time-of-addition studies
      indicated that BMS 182,193 could be added as late as 27 h after infection and
      still retain its antiviral activity. To directly show that the activity of these
      compounds in culture was due to inhibition of proteolytic cleavage, the levels of
      HIV-1 gag processing in chronically infected cells were monitored by Western blot
      (immunoblot) analysis. All compounds blocked the processing of p55 in a dose
      dependent manner, with 50% effective doses of 0.4 to 2.4 microM. To examine the
      reversibility of BMS 186,318, chronically infected CEM-SS cells were treated with
      drug and virions purified from the culture medium. Incubation of HIV-1 particles
      in drug-free medium indicated that inhibition of p55 proteolysis was slowly
      reversible. The potent inhibition of HIV-1 during both acute and chronic
      infections indicates that these aminodiol compounds are effective anti-HIV-1
      compounds.

PMID- 7726503
TI  - Activity of carbapenem BMS-181139 against Pseudomonas aeruginosa is not dependent
      on porin protein D2.
AB  - The broad antipseudomonal spectrum of the carbapenem BMS-181139 includes clinical
      strains and laboratory mutants of Pseudomonas aeruginosa that are resistant to
      imipenem. Unlike other known carbapenems (meropenem, panipenem, biapenem, and BO
      2727), which have reduced activity against imipenem-resistant strains of P.
      aeruginosa, BMS-181139 was equally active against imipenem-susceptible (D2
      sufficient) and imipenem-resistant (D2-deficient) strains. Conversely, imipenem
      and meropenem activities were the same against the susceptible parental strains
      and their BMS-181139-resistant mutants. Whereas basic amino acids antagonized the
      antipseudomonal activities of imipenem and meropenem, they had no effect on the
      activity of BMS-181139. These results suggest that the uptake of BMS-181139 into
      pseudomonal cells occurs by a non-D2 pathway. Compared with imipenem and
      meropenem, BMS-181139 may have a slightly higher affinity for penicillin-binding
      protein 2 (PBP-2) of P. aeruginosa. The rates of resistance development to
      imipenem, meropenem, and BMS-181139 in P. aeruginosa strains were similar;
      resistance occurred at frequencies of approximately 10(-7) to 10(-8). Resistance
      to BMS-181139 in P. aeruginosa is presumed to be caused by its diminished
      permeability since no change in their penicillin-binding protein affinities or
      beta-lactamase levels could be detected. In summary, BMS-181139 is a new
      carbapenem which differs from other known carbapenems in its lack of cross
      resistance with imipenem. This difference could be explained by the permeation of
      BMS-181139 through a non-D2 channel, compared to the preferential uptake of other
      carbapenems by the D2 porin.

PMID- 7726504
TI  - Structure-activity relationships of carbapenems that determine their dependence
      on porin protein D2 for activity against Pseudomonas aeruginosa.
AB  - A number of carbapenem derivatives were examined to determine the structure
      activity relationships required for dependence on porin protein D2 for activity
      against Pseudomonas aeruginosa. As suggested by J. Trias and H. Nikaido
      (Antimicrob. Agents Chemother. 34:52-57, 1990), carbapenem derivatives, such as
      imipenem and meropenem, containing a sole basic group at position 2 of the
      molecule utilize the D2 channel for permeation through the outer membrane of
      pseudomonads; they are more active against D2-sufficient strains of P.
      aeruginosa. Our results indicated that carbapenems with a basic group at position
      1 or 6 of the molecule did not depend on the D2 channel for activity; i.e. they
      were equally active against D2-sufficient and D2-deficient pseudomonal strains.
      However, addition of a basic group at position 1 or 6 of a carbapenem derivative
      already containing a basic group at position 2 resulted in its lack of dependency
      on the D2 pathway. Comparison between meropenem and its 1-guanidinoethyl
      derivative, BMY 45047, indicated that they differed in their dependence on D2;
      while meropenem required the D2 channel for uptake, BMY 45047 activity was
      independent of D2. Meropenem and BMY 45047 had similar affinities for the
      penicillin-binding proteins of P. aeruginosa. However, BMY 45047 and meropenem
      differed in the morphological changes that they induced in pseudomonal cells.
      While meropenem induced filamentation, BMY 45047 induced filaments only in BMS
      181139-resistant mutants and not in imipenem-resistant mutants or in carbapenem
      susceptible P. aeruginosa strains. These results suggested that in Mueller-Hinton
      medium the uptake of BMY 45047 through the non-D2 pathway is more rapid than that
      of meropenem through the D2 porin. In summary, the presence of a basic group at
      position 2 of a carbapenem is important for its preferential uptake by the D2
      channel. However the addition of a basic group at position 1 or 6 of a carbapenem
      already containing a basic group at position 2 dissociates its necessity for
      porin protein D2 for activity.

PMID- 7726505
TI  - Critical influence of resistance to streptogramin B-type antibiotics on activity
      of RP 59500 (quinupristin-dalfopristin) in experimental endocarditis due to
      Staphylococcus aureus.
AB  - In order to determine the microbiological and pharmacokinetic parameters that
      best predicted the in vivo antistaphylococcal activity of the streptogramin RP
      59500 (quinupristin-dalfopristin), we evaluated the activity in rabbit aortic
      endocarditis of three regimens of quinupristin-dalfopristin against five strains
      of Staphylococcus aureus with various streptogramin B-type antibiotic resistance
      phenotypes and susceptible to streptogramin A-type antibiotics. Quinupristin
      dalfopristin was as active as vancomycin against three strains that were
      susceptible to its streptogramin B component quinupristin, including one strain
      that was inducibly resistant to erythromycin, but had a significantly decreased
      activity against two strains that were resistant to quinupristin, for all
      quinupristin-dalfopristin regimens tested (P < 0.05). The area under the
      concentration-time curve for quinupristin-dalfopristin in plasma divided by the
      MIC of quinupristin was the only parameter retained by multilinear regression
      that predicted the in vivo activity of quinupristin-dalfopristin (P = 0.0001),
      emphasizing the importance of determining the susceptibility to quinupristin in
      order to predict the in vivo activity of quinupristin-dalfopristin against S.
      aureus.

PMID- 7726506
TI  - Subinhibitory concentrations of cefpodoxime alter membrane protein expression of
      Actinobacillus actinomycetemcomitans and enhance its susceptibility to killing by
      neutrophils.
AB  - The aim of the present study was to determine the effect of the antibiotic
      cefpodoxime on the gram-negative periodontopathic microorganism Actinobacillus
      actinomycetemcomitans and its interaction with elements of the host immune
      system. Growth of A. actinomycetemcomitans in subinhibitory concentrations of
      cefpodoxime induced morphological changes in the bacteria, causing the organisms
      to grow as filaments rather than coccobacilli. Growth in cefpodoxime did not
      render these bacteria susceptible to killing by serum, nor did it abrogate the
      requirement for serum opsonins to support the bactericidal activity of
      neutrophils. Cefpodoxime enhanced the susceptibility of A. actinomycetemcomitans
      to the bactericidal activity of neutrophils. In the presence of suitable
      opsonins, neutrophils were able to kill four times as many cefpodoxime-induced A.
      actinomycetemcomitans filaments as untreated A. actinomycetemcomitans CFU. This
      effect was due to antibiotic actions on the bacterium and not on the neutrophil.
      At inhibitory concentrations, the bactericidal activities of cefpodoxime and
      neutrophils were additive, and cefpodoxime did not interfere with the normal
      functioning of the neutrophils. Concomitant with these morphological and
      functional changes, the expression of two outer membrane proteins (66 and 29 kDa)
      and one inner membrane protein (57 kDa) was decreased in A. actinomycetemcomitans
      grown in cefpodoxime. The concentration range over which cefpodoxime is effective
      against A. actinomycetemcomitans in vivo may be extended by the ability of
      subinhibitory concentrations to enhance the susceptibility of this organism to
      host immune defenses.

PMID- 7726507
TI  - E-4695, a new C-7 azetidinyl fluoronaphthyridine with enhanced activity against
      gram-positive and anaerobic pathogens.
AB  - E-4695, (-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-cyclopropyl-1,4- dihydro
      6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid, is a new fluorinated
      naphthyridine with an azetidine moiety. The MICs of E-4695 at which 90% of the
      isolates were inhibited (MIC90s) were 0.06 to 0.5 microgram/ml for gram-positive
      cocci, including species of the genera Staphylococcus, Streptococcus, and
      Enterococcus, and the MIC90s against gram-negative pathogens such as members of
      the family Enterobacteriaceae (with the exception of Providencia spp. [MIC90, 8
      micrograms/ml]) and Pseudomonas aeruginosa were 0.015 to 0.5 microgram/ml. E-4695
      inhibited 90% of the Clostridium perfringens and Bacteroides fragilis isolates at
      0.25 and 4 micrograms/ml, respectively. Against gram-positive cocci the potency
      of E-4695 was 2- to 8-fold higher than that of ciprofloxacin, 4- to 8-fold higher
      than that of ofloxacin, and 8- to 16-fold higher than that of fleroxacin. Against
      enteric bacteria and P. aeruginosa the potency of E-4695 was, in general, similar
      to that of ciprofloxacin and eightfold higher than those of ofloxacin and
      fleroxacin. E-4695 was four- and eightfold more potent than ciprofloxacin against
      C. perfringens and B. fragilis isolates, respectively. E-4695 and ciprofloxacin
      showed similar properties when the effects of pH or magnesium concentration were
      tested on them. E-4695 and ciprofloxacin had substantial reductions of activity
      only when pH decreased below 4.8. E-4695 and ciprofloxacin activities were not
      markedly affected by the presence of 5 or 10 mM Mg2+. The presence of serum and
      human urine at pH 7.2 decreased the activity of E-4695 between two- and fourfold.
      After an oral dose of 50 mg/kg of body weight, the maximum level in serum, the
      biological half-life, and the area under the concentration-time curve from 0 to
      10 h for E-4695 were 13.2 microgram/ml, 3.3 h, and 45.6 microgram . h/ml,
      respectively. The area under the concentration-time curve from 0 to 4 h for
      ciprofloxacin was 2.3 microgram . h/ml at the same dose. Fifty-percent effective
      doses (ED50S) against Staphylococcus aureus HS-93 infections in mice were 4.5
      mg/kg with E-4695 and 37.6 mg/kg with ciprofloxacin. Infection with Streptococcus
      pneumoniae 29206 was more effectively treated with E-4695 (ED50, 41,2 mg/kg) than
      with ciprofloxacin (ED50, 200 mg/kg). The ED50 of E-4695 for infections with
      Streptococcus pneumoniae 1625 was 132.2 mg/kg; ciprofloxacin was ineffective at
      400 mg/kg against this strain. E-4695 was also more potent than ciprofloxacin in
      treatment of infections caused by gram-negative organisms such as Escherichia
      coli HM-42 (ED50S, 1.0 and 3.9 mg/kg, respectively). The ED50S of E-4695 and
      ciprofloxacin were 33.0 and 145.5 mg/kg against P. aeruginosa HS-116 and 9.6 and
      18.9 mg/kg against P. aeruginosa B-120, respectively. The therapeutic efficacy of
      E-4695 may depend not only on its in vitro activity but also on its improved
      pharmacokinetic properties.

PMID- 7726508
TI  - Multidrug resistance in Candida albicans: disruption of the BENr gene.
AB  - The BENr gene of Candida albicans, which confers resistance on susceptible
      strains of Saccharomyces cerevisiae to six structurally and functionally
      unrelated drugs, was described recently (R. Ben-Yaacov, S. Knoller, G. Caldwell,
      J. M. Becker, and Y. Koltin, Antimicrob. Agents Chemother. 38:648-652, 1994).
      This gene bears similarity to membrane proteins encoding antibiotic resistance in
      prokaryotes and eukaryotes. The effect of disruption of this gene on viability
      and drug susceptibility was determined. The results indicate that the gene is not
      essential but its inactivation leads to susceptibility to three of the four drugs
      tested. Inactivation of this gene did not increase the susceptibility of the
      mutant to benomyl, suggesting that C. albicans has other mechanisms of
      resistance, some of which may be additional efflux pumps that confer resistance
      to this tubulin-destabilizing agent.

PMID- 7726509
TI  - Molecular characterization of nine different types of mutants among 107 inhibitor
      resistant TEM beta-lactamases from clinical isolates of Escherichia coli.
AB  - DNA-DNA hybridization and sequencing were performed to determine the molecular
      basis of resistance to clavulanic acid in 107 inhibitor-resistant TEM (IRT)
      enzymes produced by Escherichia coli clinical isolates. These beta-lactamases
      derived from TEM-1 enzyme focused at pI 5.2 (n = 68) or 5.4 (n = 39) and were
      very poorly inhibited by clavulanic acid compared with TEM-1 enzyme. Results
      showed that the amino acid sequences of 84 of the 107 enzymes differ from TEM-1
      by one or two substitutions previously described: Arg-244-->Ser (IRT-2) in 22
      strains, Met-69-->Leu (TEM-33) in 17 strains, Met-69-->Val (TEM-34) in 14
      strains, Met-69-->Ile (IRT-3) in 6 strains, Met-69-->Leu associated with Asn-276-
      >Asp (IRT-4) in 13 strains, and Met-69-->Val associated with Asn-276-->Asp (TEM
      36) in 12 strains. A new combination, Met-69-->Ile with Asn-276-->Asp, was found
      in 20 strains and was called IRT-8. Two IRT enzymes not previously described were
      characterized. The substitution Met-69-->Val associated with a novel substitution
      Arg-275-->Leu occurred in one strain. The combination Met-69-->Leu and Asn-276-
      >Asp was associated with the novel substitution Trp-165-->Arg in two strains.
      These two novel enzymes were called IRT-9 and IRT-10, respectively. The
      implication of these novel mutated positions, 165 and 275, in resistance to
      inactivation by clavulanate was supported by crystallographic data on the TEM-1
      enzyme and results of site-directed mutagenesis. Molecular characterization of
      these mutants showed great diversity among the genes coding for inhibitor
      resistant TEM enzymes produced by clinical E. coli isolates.

PMID- 7726510
TI  - Amoxicillin pharmacokinetics in preterm infants with gestational ages of less
      than 32 weeks.
AB  - The multiple-dose pharmacokinetics of amoxicillin (AM [administered twice daily
      in a 25-mg/kg of body weight intravenous dose]) in 17 preterm infants (11 males;
      gestational age, 29 +/- 1.9 weeks; birth weight, 1,175 +/- 278 g) were evaluated
      on day 3 of life. Blood samples were collected from an arterial catheter at 0,
      0.5, 1, 2, 4, 8, and 12 h after the intravenous dose. A high-performance liquid
      chromatography method was used to determine AM concentrations in serum. AM
      pharmacokinetics followed a one-compartment open model. The glomerular filtration
      rates of all patients were simultaneously studied by means of the 24-h continuous
      inulin infusion technique. The elimination half-life, apparent volume of
      distribution, and total body clearance of AM (mean +/- standard deviation) were
      6.7 +/- 1.7 h, 584 +/- 173 ml, and 62.4 +/- 23.3 ml/h, respectively. The mean (+/
      standard deviation) AM peak and trough levels were 53.6 +/- 9.1 and 16.0 +/- 4.9
      mg/liter, respectively. All infants had a serum trough level above 5 mg/liter.
      The total body clearance and apparent volume of distribution of AM and the
      clearance of inulin increased significantly with increasing gestational age. The
      total body clearance of AM (1.0 +/- 0.4 ml/min) and the clearance of inulin (1.0
      +/- 0.3 ml/min) were similar. The total body clearance of AM increased
      significantly with increasing clearance of inulin. We conclude that an AM dose of
      25 mg/kg every 12 h given to preterm infants in the first week of life with
      gestational ages of less than 32 weeks results in serum levels well above the MIC
      for major microorganisms involved in neonatal infections.

PMID- 7726511
TI  - Enhancement of antibiotic susceptibility and suppression of Mycobacterium avium
      complex growth by poloxamer 331.
AB  - The resistance of Mycobacterium avium complex (MAC) to antibiotics is thought to
      be enhanced by its outer glycolipid layer, which protects the organisms from
      antibiotics and host defense mechanisms. We hypothesized that surfactants which
      disrupt the lipid barrier might be of therapeutic value. We evaluated the ability
      of 10 poloxamer surfactants to inhibit the growth of MAC organisms and to
      potentiate antimycobacterial drug activity in broth culture using a radiometric
      assay. Very large, small, or hydrophilic poloxamers had little or no effect.
      However, certain hydrophobic poloxamers, especially P331, retarded the growth of
      most isolates of MAC and produced a synergistic effect with rifampin. The MIC of
      rifampin required to inhibit the growth of MAC was reduced from a mean of 14.6
      micrograms/ml (range, 4 to > 32 micrograms/ml) to 1.4 micrograms/ml (range, <
      1.125 to 4 micrograms/ml) by 1.0 mg of P331 per ml (P < 0.01). Enhancement of
      antibiotic susceptibility was observed with concentrations of poloxamer as low as
      10 micrograms/ml. These studies suggest that P331 might be useful in increasing
      the effectiveness of antibiotic therapy of MAC infections.

PMID- 7726512
TI  - In vitro activity of the benzoxazinorifamycin KRM-1648 against drug-susceptible
      and multidrug-resistant tubercle bacilli.
AB  - We investigated the activity of benzoxazinorifamycin (KRM-1648) against several
      drug-susceptible and multidrug-resistant strains of tubercle bacilli. Since KRM
      1648 is a rifamycin derivative, we included some strains of Mycobacterium
      tuberculosis resistant to rifampin (RIF) among the multidrug-resistant strains.
      For RIF-susceptible strains, the MIC of KRM-1648 was much lower than that of RIF
      (MICs of KRM-1648 and RIF at which 90% of strains are inhibited, < or = 0.015 and
      < or = 0.25 micrograms/ml, respectively). The MBC of KRM-1648 (range, 0.007 to
      0.03 microgram/ml) was also much lower than that of RIF (range, 0.5 to 1.0
      microgram/ml). Postantibiotic effect studies with KRM-1648 showed a rapid
      reduction in the CFU counts with an exposure of 24 h or more, and its sterilizing
      effect was maintained even up to 21 days thereafter. Parallel postantibiotic
      effect studies with RIF showed a less significant effect with a faster recovery
      of growth, and RIF failed to sterilize the organisms even after 72 h of exposure.
      KRM-1648 at 0.125 and 0.25 microgram/ml caused complete inhibition of
      intracellular growth of M. tuberculosis in J774 A.1 macrophages after 48 h of
      exposure. After a similar exposure time RIF at a concentration of 0.25
      microgram/ml caused complete inhibition of growth, but a concentration of 0.125
      microgram/ml caused only a 50% reduction in growth compared with that of controls
      at day 7. With 24 h of pulsed exposure of the intracellular organisms to 0.25
      micrograms of the drugs per ml, KRM-1648 caused complete inhibition of
      intracellular growth, while RIF caused only moderate inhibition of intracellular
      growth. These findings suggest that KRM-1648 is a potentially useful drug for the
      treatment of tuberculosis.

PMID- 7726513
TI  - Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric
      therapy for fever in granulocytopenic patients with cancer. The International
      Antimicrobial Therapy Cooperative Group of the European Organization for Research
      and Treatment of Cancer.
AB  - Gram-positive bacteria have become the predominant infecting organisms in
      granulocytopenic cancer patients. Empiric antibiotic regimens used in febrile
      neutropenic patients often include an extended-spectrum cephalosporin, but the
      response to therapy in gram-positive coccal bacteremia has been unsatisfactory.
      Thus, new antibiotics with better activity against gram-positive bacteria should
      be tested. The objective of this prospective randomized controlled study was to
      evaluate and compare the efficacy and tolerance of piperacillintazobactam plus
      amikacin with that of ceftazidime plus amikacin, the standard regimen of the
      International Antimicrobial Therapy Cooperative Group of the European
      Organization for Research and Treatment of Cancer, in the empiric treatment of
      febrile granulocytopenic cancer patients. A total of 858 episodes were eligible
      for this study, and 706 episodes were assessable for efficacy. The antibiotic
      treatment was successful in 210 (61%) of 342 episodes in the piperacillin
      tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with
      ceftazidime plus amikacin (P = 0.05). The time to defervescence was significantly
      shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in
      the piperacillin-tazobactam-amikacin group. A significant difference in response
      to bacteremic infections between the two patient groups was found: piperacillin
      tazobactam plus amikacin was successful in 40 of 80 episodes (50%), and
      ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05).
      A multivariate analysis showed that the probability of failure was significantly
      greater with ceftazidime plus amikacin than with piperacillin-tazobactam plus
      amikacin (P = 0.02). This trial suggests that piperacillin-tazobactam plus
      amikacin is more effective than ceftazidime plus amikacin for the empiric
      treatment of fever and bacteremia in granulocytopenic cancer patients. Although
      cutaneous reaction was more frequently associated with piperacillin-tazobactam
      plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively
      mild and its incidence was comparable to that of other penicillin compounds.

PMID- 7726514
TI  - Cloning of multidrug resistance gene pqrA from Proteus vulgaris.
AB  - The multiple antibiotic resistance gene pqrA was cloned from the chromosomal DNA
      of a clinical isolate of Proteus vulgaris 881051 into Escherichia coli KY2563.
      The MICs of quinolones tetracycline, cephalosporin, and chloramphenicol for
      transformant strain DNS7020 were from 8 to 32 times higher than those for the
      parent strain, KY2563. The level of expression of outer membrane protein F (OmpF)
      by DNS7020 was lower than that of KY2563 but not as low as that of an OmpF
      deficient control strain. The 1.4-kb fragment containing the pqrA gene had an
      open reading frame encoding a polypeptide of 122 amino acid residues with a
      molecular weight of about 14,000, which was consistent with the experimental
      value identified by the Maxicell method. The putative PqrA polypeptide showed
      significant amino acid sequence similarity to the E. coli proteins SoxS and MarA.
      These polypeptides are strongly conserved in predicted helix-turn-helix DNA
      binding domains. The MarA protein, which is responsible for multiple antibiotic
      resistance in E. coli, also decreases OmpF expression. Moreover, the SoxS
      protein, which is characterized as a superoxide response regulon of E. coli, has
      also been shown to increase resistance to many structurally unrelated
      antibiotics. The soxS gene increases superoxide dismutase levels in addition to
      decreasing OmpF expression. The expression level of superoxide dismutase with
      DNS7020 was about 1.5 times higher than that with KY2563. These findings suggest
      that the pqrA gene in P. vulgaris confers multidrug resistance in a way similar
      to that of the soxS and marA genes in E. coli.

PMID- 7726516
TI  - In vitro and in vivo antistaphylococcal activities of L-695,256, a carbapenem
      with high affinity for the penicillin-binding protein PBP 2a.
AB  - L-695,256 is a synthetic carbapenem beta-lactam antibiotic that binds with a high
      degree of affinity to penicillin-binding protein (PBP) PBP 2a, the protein that
      mediates staphylococcal resistance to methicillin. The concentration of L-695,256
      that inhibited binding of radiolabeled [3H]penicillin to PBP 2a by 50% was 1.2
      micrograms/ml, whereas they were 14 and 68 micrograms/ml for penicillin and
      imipenem, respectively. Cell wall synthesis, determined by incorporation of
      [14C]N-acetylglucosamine into whole cells, was inhibited by 50% at concentrations
      of 1.3, 26, and 132 micrograms/ml for L-695,256, penicillin, and imipenem,
      respectively, for the methicillin-resistant strain COL. Growth of cells of each
      of two homogeneously resistant strains, COL and 76, was completely inhibited by 4
      micrograms of L-695,256 per ml, whereas growth was inhibited by 100 micrograms or
      more of penicillin or imipenem per ml. The efficacies of L-695,256 (10 mg/kg
      given three times daily [t.i.d.]), imipenem (37.5 mg/kg t.i.d.), penicillin
      (300,000 units/kg t.i.d.), and vancomycin (25 mg/kg given twice daily) were
      compared in the rabbit model of aortic valve endocarditis established with these
      homogeneous strains. After 4 days of treatment, mean bacterial densities in
      aortic valve vegetations were reduced by 4.0 to 5.8 log10 CFU/g for L-695,256,
      1.0 to 1.8 log10 CFU/g for imipenem, -1.1 to 3.9 log10 CFU/g for penicillin, and
      1.1 to 3.0 log10 CFU/g for vancomycin in comparison to the densities of controls.
      Compounds such as L-695,256 that are bound by PBP 2a with a high degree of
      affinity are likely to be extremely effective in the treatment of infections
      caused by methicillin-resistant staphylococci.

PMID- 7726515
TI  - New extended-spectrum TEM-type beta-lactamase from Salmonella enterica subsp.
      enterica isolated in a nosocomial outbreak.
AB  - A new extended-spectrum beta-lactamase was detected in a lactose-positive
      Salmonella enterica subsp. enterica strain that caused a nosocomial outbreak
      involving eight patients in a pediatric cardiology unit. This strain showed high
      levels of resistance to ceftazidime and aztreonam and relatively low levels of
      resistance to cefotaxime and ceftriaxone. Resistance was associated with a
      conjugative plasmid of 59 kb, which encoded a new beta-lactamase with an
      isoelectric point of 5.9 that strongly hydrolyzed ceftazidime and to a much
      lesser extent hydrolyzed cefotaxime. The enzyme activity was inhibited by
      clavulanate. The corresponding bla gene was cloned and sequenced. The deduced
      amino acid sequence showed three significant amino acid replacements with respect
      to the TEM-1 sequence: Arg-164-->His, Glu-240-->Lys, and Thr-265-->Met. This
      combination is unique among extended-spectrum beta-lactamases and served to
      characterize the new enzyme, TEM-27.

PMID- 7726517
TI  - Tobramycin uptake in Escherichia coli membrane vesicles.
AB  - The uptake of tobramycin was measured in Escherichia coli membrane vesicles
      prepared in KMES [K(+)-2-(N-morpholino)ethanesulfonic acid] buffer at pH 6.6.
      Uptake occurred in vesicles energized with ascorbic acid and phenazine
      methosulfate, in which the electrical potential (delta psi) was -120 mV, but not
      in vesicles energized with D-lactate (delta psi = -95 mV). The addition of
      nigericin to vesicles energized with D-lactate did not induce tobramycin uptake
      despite an increase in delta psi to -110 mV. However, when delta psi was
      increased or decreased by the addition of nigericin or valinomycin, respectively,
      uptake in vesicles energized with ascorbic acid and phenazine methosulfate was
      stimulated or inhibited, respectively, confirming studies with whole cells
      showing that uptake of aminoglycosides is gated by delta psi rather than by
      proton motive force (delta microH+) or delta pH. N-ethylmaleimide prevented
      uptake, suggesting that the aminoglycoside transporter is a cytoplasmic membrane
      protein with accessible sulfhydryl groups. The observation that uptake is gated
      in vesicles as well as in whole cells suggested that diffusion occurs through a
      voltage-gated channel. In vesicles preloaded with tobramycin, no efflux occurred
      after the addition of the protonophore carbonyl cyanide m-chlorophenylhydrazone.
      In susceptible cells, aminoglycosides themselves decreased the magnitude of delta
      psi. We propose a mechanism of aminoglycoside-induced killing in which
      aminoglycosides themselves close the voltage-gated channel by decreasing the
      magnitude of delta psi. Channel closure causes aminoglycosides accumulated prior
      to the fall in delta psi to be trapped, which in turn causes irreversible uptake
      and subsequent bactericidal effects.

PMID- 7726519
TI  - Development of multiple-antibiotic-resistant (Mar) mutants of Pseudomonas
      aeruginosa after serial exposure to fluoroquinolones.
AB  - Laboratory-derived fluoroquinolone-resistant mutants were created by serially
      passaging wild-type Pseudomonas aeruginosa on fluoroquinolone-containing agar to
      obtain high-level fluoroquinolone resistance (e.g., ciprofloxacin MIC of 1,024
      micrograms/ml). With increases of 4- to 32-fold in MICs of fluoroquinolones,
      these organisms demonstrated (relative to wild-type) normal morphology,
      resistance to fluoroquinolones only, no change in fluoroquinolone uptake, and no
      change in lipopolysaccharide profiles or outer membrane protein profiles.
      Complementation with wild-type Escherichia coli gyrA restored fluoroquinolone
      susceptibility, suggesting that these were gyrA mutants. After 4- to 32-fold
      increases in fluoroquinolone MICs (with continued passage on fluoroquinolone
      containing agar) isolates demonstrated altered morphology, a multiple-antibiotic
      resistant (Mar) phenotype (including cross-resistance to beta-lactams,
      chloramphenicol, and tetracycline), reduced fluoroquinolone uptake and altered
      outer membrane proteins (reductions in the 25- and 38-kDa bands as well as
      several bands in the 43- to 66-kDa region). Complementation with wild-type E.
      coli gyrA partially reduced the level of fluoroquinolone resistance by
      approximately 8- to 32-fold, suggesting that these mutants displayed both gyrA
      and non-gyrA mutations.

PMID- 7726520
TI  - Comparative efficacies of ciprofloxacin and pefloxacin alone or in combination
      with fosfomycin in experimental endocarditis induced by multidrug-susceptible and
      -resistant Pseudomonas aeruginosa.
AB  - The in vivo efficacy of ciprofloxacin or pefloxacin alone or in combination with
      fosfomycin was evaluated in experimental aortic valve endocarditis induced in 133
      rabbits by a multidrug-susceptible or multidrug-resistant strain of Pseudomonas
      aeruginosa. Therapy was initiated early (12 h after infection), when bacterial
      counts in aortic valve vegetations were relatively low, or late (48 h after
      infection), when vegetations contained a larger inoculum. Antibodies were
      administered as a continuous 24-h intravenous infusion. Mean steady-state levels
      of ciprofloxacin (64 mg/kg), pefloxacin (64 mg/kg), and fosfomycin (300 mg/kg) in
      serum were 2.5, 4.2, and 63.9 mg/liter, respectively. For the multidrug
      susceptible strain, all regimens except pefloxacin alone significantly reduced
      the number of CFU per gram of vegetation versus controls, whether treatment was
      performed early or late. For the multidrug-resistant strain, none of the regimens
      showed differences from untreated controls, except ciprofloxacin-fosfomycin,
      which significantly reduced bacterial counts in vegetations compared with
      controls when therapy was begun early (4.1 +/- 1.1 log10 CFU/g of vegetation; P <
      0.001 versus the control). These data suggest that combination of fosfomycin with
      ciprofloxacin or pefloxacin is more effective than ciprofloxacin or pefloxacin
      alone for the therapy of severe infections caused by multidrug-susceptible P.
      aeruginosa.

PMID- 7726518
TI  - CP-115,953 stimulates cytokine production by lymphocytes.
AB  - The cytotoxic quinolone CP-115,953 specifically exerts its inhibitory effect upon
      eukaryotic topoisomerase II. CP-115,953 stimulates DNA cleavage mediated by
      topoisomerase II with a potency approximately 600 times greater than that of
      ciprofloxacin, a quinolone antibacterial agent that currently is in clinical use.
      Because ciprofloxacin has been reported to strongly enhance interleukin-2
      production, we considered it important to study the effect of CP-115,953 on
      interleukin-2 and gamma interferon (IFN-gamma) mRNA and protein expression in
      mitogen-stimulated human peripheral blood lymphocytes. For comparison, novobiocin
      and the antineoplastic drug etoposide were also included in the study. CP-115,953
      (25 microM) enhanced interleukin-2 mRNA levels up to 8-fold and IFN-gamma mRNA
      concentrations up to 6.5-fold. In contrast, ciprofloxacin (282 microM) induced
      mRNAs for interleukin-2 and IFN-gamma up to 20-fold and 7.8-fold, respectively.
      However, CP-115,953 showed more prolonged kinetics of IFN-gamma mRNA production
      than ciprofloxacin. At high concentrations (> or = 141 microM), ciprofloxacin was
      a greater inducer of interleukin-2 production and exhibited a higher level of
      stimulatory action than CP-115,953 on IFN-gamma synthesis. At low concentrations,
      however, CP-115,953 (< or = 25 microM) was more potent than ciprofloxacin in
      inducing interleukin-2 and IFN-gamma synthesis. Etoposide or novobiocin did not
      influence cytokine mRNA expression. Thus, among the topoisomerase II inhibitors
      tested, fluoroquinolones are unique in stimulating cytokine synthesis in
      lymphocyte cultures.

PMID- 7726521
TI  - Conjugative transposition of Tn916-related elements from Enterococcus faecalis to
      Escherichia coli and Pseudomonas fluorescens.
AB  - We studied the ability of transposons Tn916, Tn1545, and Tn916-Km, a Tn916
      derivative expressing kanamycin resistance, to be conjugatively transferred from
      Enterococcus faecalis to various gram-negative bacteria. Our results demonstrate
      that these types of elements can carry out conjugative transposition from the
      chromosome of E. faecalis to those of Escherichia coli and Pseudomonas
      fluorescens and that the accomplishment of this event depends on the donor
      potential of the E. faecalis transposon delivery strain. Since the tet(M) gene
      does not confer a selectable level of tetracycline resistance to gram-negative
      bacteria such as E. coli, the presence of another marker(s) readily expressed in
      these recipients is required for the detection of this type of transfer. Conjugal
      transfer of Tn916-Km from E. faecalis to E. coli is not restricted by the EcoK
      restriction system, nor does it depend on the presence of functional homologous
      recombination system and integration host factor proteins in the recipient
      bacteria.

PMID- 7726522
TI  - Effect of aerobic and anaerobic environments on antistaphylococcal activities of
      five fluoroquinolones.
AB  - A previously established in vitro pharmacodynamic system was used to evaluate the
      antistaphylococcal activities of five fluoroquinolones under both aerobic and
      anaerobic conditions. Staphylococcus aureus ATCC 29213 was exposed to a 5
      micrograms/ml concentration of each of the following fluoroquinolones:
      ciprofloxacin, ofloxacin, temafloxacin, sparfloxacin, and clinafloxacin. Terminal
      elimination half-lives of 4, 6, 8, 8, and 13 h were simulated for the respective
      drugs. Each fluoroquinolone was bactericidal under both aerobic and anaerobic
      conditions. However, the bactericidal activity of each fluoroquinolone was
      delayed by anaerobiosis. This difference in fluoroquinolone activity under
      aerobic and anaerobic conditions could not be attributed to any particular
      parameter or physiochemical property but was most likely caused by a combination
      of factors (e.g., variations in hydrophobicity, intracellular pH, antibiotic
      concentration, and structure-activity relationships). Fluoroquinolone uptake
      studies were also performed to investigate the possibility of active, energy
      dependent transport mechanisms in S. aureus ATCC 29213. Uptake studies indicated
      that active efflux does occur in S. aureus ATCC 29213.

PMID- 7726523
TI  - Pharmacokinetics and tissue penetration of the new fluoroquinolone grepafloxacin.
AB  - A single 400-mg oral dose of grepafloxacin (OPC-17116) was given to each of six
      healthy male volunteers, and the concentrations of the drug in plasma,
      cantharides-induced inflammatory fluid, and urine were measured over the
      subsequent 12 h. The mean peak concentration in plasma of 1.5 micrograms/ml was
      attained at a mean time of 2.0 h postdose. The mean peak concentration in
      inflammatory fluid of 1.1 micrograms/ml was attained at a mean time of 4.8 h
      postdose. The mean elimination half-life in plasma was 5.2 h, and that in
      inflammatory fluid was 12.7 h. The overall penetration into inflammatory fluid
      was 180.6% (or 133% if one aberrant result from one volunteer is excluded).
      Recovery of the drug in urine during the first 24 h postdose was 8.3% of the
      administered dose. Our results indicate that a once- or twice-daily dosage of
      grepafloxacin should be adequate to treat systemic infections caused by most
      bacterial pathogens.

PMID- 7726524
TI  - Skin uptake, distribution, and elimination of antimony following administration
      of sodium stibogluconate to patients with cutaneous leishmaniasis.
AB  - We examined in this study the pharmacokinetics of Sb in the affected skin and
      normal skin of patients treated with sodium stibogluconate for cutaneous
      leishmaniasis and compared the results with those for the blood. The procedure
      was fully explained, and a written consent was obtained from each of nine
      patients. After a dose of sodium stibogluconate equivalent to 600 mg of Sb was
      administered intramuscularly, small skin biopsies were collected under local
      anesthesia at different time intervals from the circumferences of the lesions and
      simultaneously from normal skin. Antimony was measured in these biopsies after
      suitable ashing and processing by flameless atomic absorption spectrophotometry.
      The means (with standard errors of the means in parentheses) of the peak
      concentration, time to peak concentration, area under the curve, half-life, and
      mean residence time in lesions were 5.02 (1.43) micrograms/g, 2.1 (0.4) h, 32.8
      (6.1) micrograms.h/g, 6.88 (0.54) h, and 10.4 (1.2) h, respectively, and those in
      normal skin were 6.56 (2.01) micrograms/g, 2.6 (0.8) h, 44.0 (15.8)
      micrograms.h/g, 5.44 (0.83) h, and 8.08 (1.34) h, respectively. There was no
      significant difference in any of these parameters between lesions and normal
      skin, whereas the differences in peak concentration, half-life, and mean
      residence time between lesions and whole blood were significant (P < or = 0.05).
      The penetration of Sb into skin, either affected or normal, as measured by the
      skin/blood area under the curve ratio appears to be complete, but the disposition
      is slow compared with that from the blood.

PMID- 7726525
TI  - Relationship between quinolone use and emergence of ciprofloxacin-resistant
      Escherichia coli in bloodstream infections.
AB  - From 1988 to 1992, 27 of 855 cases of Escherichia coli bacteremia in
      nonneutropenic adult patients observed at our hospital were due to ciprofloxacin
      resistant (CIPRO-R) strains. Eighteen episodes (67%) were community acquired, and
      nine (33%) were nosocomially acquired. Overall, the rates of E. coli bacteremia
      caused by CIPRO-R strains increased steadily from 0% in 1988 to 7.5% in 1992 (P <
      0.01). There was a statistically significant correlation between the incidence of
      CIPRO-R E. coli bacteremia and the upward trend in fluoroquinolone (norfloxacin
      and ciprofloxacin) use in the community (r = 0.974; P = 0.005) as well as in the
      hospital (r = 0.975; P = 0.005). When we compared the 27 case patients with 54
      simultaneous control patients who had ciprofloxacin-susceptible E. coli
      bacteremia, the case patients more frequently had chronic underlying diseases (71
      versus 37%; P = 0.004), urinary tract infection (74 versus 50%; P = 0.03), prior
      surgery (22 versus 6%; P = 0.02), and prior fluoroquinolone use (63 versus 4%; P
      < 0.001). A logistic regression analysis identified prior quinolone use as the
      only independent risk factor for CIPRO-R E. coli bacteremia. In conclusion, our
      study shows a significant correlation between ciprofloxacin resistance and
      fluoroquinolone use and indicates that prior fluoroquinolone use seems to be the
      most important risk factor for CIPRO-R E. coli bacteremia.

PMID- 7726526
TI  - Right-sided endocarditis caused by Staphylococcus aureus in drug abusers.
AB  - A prospective, open, and randomized study of right-sided endocarditis caused by
      Staphylococcus aureus in drug abuse patients is reported. The following
      parenteral treatments were compared. Group A patients were treated with 2 g of
      cloxacillin every 4 h and 1.5 mg of gentamicin per kg of body weight every 8 h
      for 2 weeks. Group B patients were treated with teicoplanin at 10 mg/kg/12 h on
      the 1st to 3rd days, 6 mg/kg/12 h on the 4th to 7th days, and 7 mg/kg/24 h on the
      8th days. Drug abusers with bacteremia caused by S. aureus and suggestive signs
      of endocarditis were included. Clinical failures were observed in one patient in
      group A and in four of six patients in group B. Three patients in group B
      developed breakthrough bacteremia with teicoplanin-susceptible strains on days
      +6, +14, and +19. Serum teicoplanin levels and serum bactericidal titers showed a
      decrease in the 2nd week, when dosages received were 7 mg/kg/day. In conclusion,
      in treatment of right-sided endocarditis caused by S. aureus in drug abusers with
      teicoplanin, the use of dosages of 7 mg/kg/day is not recommended even if
      patients have received dosages of 12 mg/kg/day during the 1st week.

PMID- 7726527
TI  - Polymyxin B stimulates production of complement components and cytokines in human
      monocytes.
AB  - Polymyxin B (PmB), an agent often used to neutralize the effects of bacterial
      lipopolysaccharide (LPS), was shown to exert a dose-dependent stimulatory effect
      on the biosynthesis of C3, factor B, interleukin-6 (IL-6), and granulocyte
      macrophage colony-stimulating factor (GM-CSF) in human monocytes. A low dose of
      PmB (1 to 5 micrograms/ml) efficiently suppressed the LPS-induced (1 or 100
      ng/ml) production of IL-6, GM-CSF, and factor B, but not the C3 production
      induced by 100 ng of LPS per ml. A reduced level of GM-CSF may have contributed
      to the persisting high C3 concentrations and the apparent lack of LPS inhibition
      in the latter situation, since GM-CSF is an inhibitor of monocyte C3
      biosynthesis.

PMID- 7726528
TI  - Antibacterial activities of cefprozil compared with those of 13 oral cephems and
      3 macrolides.
AB  - Thirteen oral cephems (cefprozil, loracarbef, cefaclor, cefuroxime axetil,
      cefpodoxime proxetil, cefetamet pivoxil, cefixime, cefdinir, cefadroxil,
      cephradine, cephalexin, cefatrizine, and cefroxadine), the cephalosporin class
      representative cephalothin, cefazolin, and the macrolides erythromycin,
      clarithromycin, and azithromycin were compared for their antibacterial activities
      against 790 recent clinical isolates. These oral agents differed in their spectra
      and antibacterial potencies against community-acquired pathogens.

PMID- 7726529
TI  - Susceptibilities of fluoroquinolone-resistant strains of Campylobacter jejuni to
      11 oral antimicrobial agents.
AB  - The resistance of Campylobacter jejuni strains to the fluoroquinolones is
      increasingly frequent, and in our area it reaches nearly 50%. We studied the
      susceptibilities of 60 of these strains to 11 oral antibiotics. All strains
      except one were susceptible to the macrolides tested, with azithromycin being the
      most active agent tested. Of the rest of the antibiotics studied, amoxicillin
      clavulanic acid, clindamycin, and fosfomycin displayed good in vitro activities.
      Knowledge of the susceptibilities of these microorganisms to a varied group of
      oral agents is necessary in view of the appearance of multiresistant strains,
      such as those included in our series.

PMID- 7726530
TI  - Aminoglycoside dosing weight correction factors for patients of various body
      sizes.
AB  - Prior investigations have suggested the use of a dosing weight correction factor
      of ideal body weight (IBW) plus 40% excess body weight (EBW, where EBW = total
      body weight [TBW] - IBW) to determine the weight to use for aminoglycoside dosing
      in morbidly obese (TBW/IBW ratio, > 2) patients. Little data are available to
      provide dosing information for underweight or moderately obese patients. We
      investigated aminoglycoside pharmacokinetics in 1,708 patients receiving
      gentamicin and tobramycin. Patients were stratified into underaverage-weight or
      overweight weight categories based on both TBW/IBW ratio and body mass index
      (weight/height2 ratio), which has been shown to correlate with physiologic
      estimates of body fat. Regression analyses revealed that the TBW/IBW ratio
      predicts the volume of distribution. Dosing weight correction factors to give
      equivalent predicted peak aminoglycoside concentrations with a 2-mg/kg loading
      dose are 1.13 times the TBW for underweight patients and 0.43 times the EBW plus
      IBW for overweight patients. There were no large differences between the dosing
      weight correction factors derived from IBW- and body mass index-based
      classification systems. These data generate useful aminoglycoside dosing weight
      equations for both underweight and overweight patients.

PMID- 7726531
TI  - Effect of inflammation on intraocular penetration of intravenous ofloxacin in
      albino rabbits.
AB  - The effect of inflammation on the intraocular penetration of ofloxacin was
      studied in 20 albino rabbits (New Zealand White). Inflammation was induced in the
      left eye by inoculation of a suspension of 10(9) CFU of heat-killed Staphyloccus
      epidermidis per 0.1 ml of saline solution (0.9%) in the midvitreous cavity. The
      other eye was kept as a control. Twenty-four hours following inoculation,
      ofloxacin was administered in the marginal ear vein at a dose of 15 mg/kg over 20
      min with an infusion pump. Animals were sacrificed at different times up to 24 h
      following drug administration. Ofloxacin levels were determined in aqueous humor,
      vitreous humor, and serum by a bioassay. Inflammation was scored on the basis of
      perilimbal and corneal reactions and vitreoretinal statuses. Inflammation had a
      relevant effect on intraocular penetration of ofloxacin, with levels in the
      ocular fluids of the inflamed eye markedly exceeding the ones of the control eye.
      In the uninflamed eye, the levels were rapidly decaying below assay sensitivity
      and were no longer detectable at approximately 5 h following drug administration
      while they were still detectable in both ocular fluids of the inflamed eye at 24
      h. Ofloxacin levels in the ocular fluids of the inflamed eye were superior to the
      MIC for several of the bacteria which commonly cause endophthalmitis, including
      Staphylococcus epidermidis, Staphylococcus aureus, most members of the family
      Enterobacteriaceae, Haemophilus influenzae, and strains of Pseudomonas
      aeruginosa.

PMID- 7726532
TI  - Fluconazole penetration into the human prostate.
AB  - Fluconazole concentrations in the serum and prostate of human volunteers
      undergoing transurethral resection for benign prostatic hypertrophy were
      measured. There was a high correlation (r = 0.783) between serum (mean = 6.6
      micrograms/ml) and tissue (mean = 1.9 micrograms/g) fluconazole concentrations,
      and these data were used to construct a model for local tissue concentrations.

PMID- 7726533
TI  - Inhibition of duck hepatitis B virus DNA replication by antiviral chemotherapy
      with ganciclovir-nalidixic acid.
AB  - The aim of this study was to examine the effects of ganciclovir and nalidixic
      acid either alone or in combination on duck hepatitis B virus DNA replication in
      vivo with particular reference to production of viral supercoiled DNA and RNA.
      The most effective antiviral response was observed in the livers of ducks treated
      by the combination therapy for 28 days, which resulted in a substantial decrease
      in the amounts of viral supercoiled DNA, relaxed circular and single-stranded
      DNA, and also viral RNA. This combination treatment was not hepatotoxic over the
      study period.

PMID- 7726534
TI  - Comparison of effects of suture and cyanoacrylate tissue adhesive on bacterial
      counts in contaminated lacerations.
AB  - We studied the effects of closing lacerations with suture or cyanoacrylate tissue
      adhesive on staphylococcal counts in inoculated guinea pig lacerations. Wounds
      closed with adhesive alone had lower counts than wounds containing suture
      material (P < 0.05). The results of a time-kill study were consistent with a
      bacteriostatic adhesive effect of the adhesive against Staphylococcus aureus.

PMID- 7726535
TI  - DNA gyrase mutations in quinolone-resistant clinical isolates of Neisseria
      gonorrhoeae.
AB  - Eight quinolone-resistant clinical isolates of Neisseria gonorrhoeae were shown
      to carry mutations in their GyrA proteins. Six isolates had a single amino acid
      change of serine to phenylalanine at the position corresponding to Ser-83 in
      Escherichia coli. In addition to the change of serine to phenylalanine, two
      isolates had another change of aspartic acid to asparagine at the position
      corresponding to Asp-87 in E. coli.

PMID- 7726536
TI  - Low-level resistance to the cephalosporin 3'-quinolone ester Ro 23-9424 in
      Escherichia coli.
AB  - Four spontaneous, single-step mutants of Escherichia coli K-12 resistant to low
      levels of the cephalosporin 3'-quinolone ester Ro 23-9424 were isolated at a
      frequency of 10(-10) to 10(-11) mutants per CFU plated. The mutants were cross
      resistant to both cephalosporin (cefotaxime) and quinolone (fleroxacin)
      components. Accordingly, they had altered porins and replicative DNA biosynthesis
      resistant to fleroxacin. There was no increase in beta-lactamase activity when
      tested with nitrocephin, and the penicillin-binding protein profiles were normal.

PMID- 7726537
TI  - Inhibitory action of lansoprazole and its analogs against Helicobacter pylori:
      inhibition of growth is not related to inhibition of urease.
AB  - The proton pump inhibitors omeprazole and lansoprazole and its acid-activated
      derivative AG-2000, which are potent and specific inhibitors of urease of
      Helicobacter pylori (K. Nagata, H. Satoh, T. Iwahi, T. Shimoyama, and T. Tamura,
      Antimicrob. Agents Chemother. 37:769-774, 1993), inhibited the growth of H.
      pylori. The growth was inhibited not only in urease-positive clinical isolates
      but also in their urease-negative derivatives which had no urease polypeptides.
      AG-1789, a derivative of lansoprazole with no inhibitory activity against H.
      pylori urease, also inhibited the growth of both strains even more strongly than
      the urease inhibitors lansoprazole and AG-2000. Furthermore, the antibacterial
      activity of omeprazole and lansoprazole was not affected by glutathione or
      dithiothreitol, which completely abolished the inhibitory activity of
      lansoprazole against H. pylori urease. These results indicated that the
      inhibitory action of these compounds against the growth of H. pylori was
      independent from the inhibitory action against urease.

PMID- 7726538
TI  - Activities of D0870, a novel triazole, against Candida lusitaniae and
      Trichosporon beigelii in experimental murine infections.
AB  - Candida lusitaniae and Trichosporon beigelii may cause life-threatening
      infections in the immunocompromised host and may be resistant to amphotericin B.
      We assessed the activities of a new triazole, D0870, against one T. beigelii and
      four C. lusitaniae strains, in comparison with those of fluconazole and
      amphotericin B. Immunosuppressed CF1 mice, intravenously infected with each
      fungal strain, received 3 days of therapy with oral D0870 (5 or 25 mg/kg of body
      weight daily), fluconazole (5 to 50 mg/kg daily), or parenteral amphotericin B (1
      or 2 mg/kg daily). Survival was significantly prolonged and kidney fungus titers
      were reduced in mice treated with D0870 compared with untreated mice (P < or =
      0.05). Treatment with D0870 was significantly more effective than that with
      amphotericin B or fluconazole in animals infected with two of the C. lusitaniae
      strains and equally effective for the remaining two C. lusitaniae strains and the
      T. beigelii strain. Fluconazole and amphotericin B failed to improve the survival
      of mice infected with one and two C. lusitaniae strains, respectively. D0870 was
      active against all the organisms tested, including those resistant to fluconazole
      and amphotericin B.

PMID- 7726539
TI  - Effect of various pentoxiphylline concentrations on macrophage inflammatory
      protein 1 alpha production.

PMID- 7726540
TI  - Resistance of the obese Zucker rat to insulin-induced feeding and to satiety
      induced by coinfusion of insulin and glucose.
AB  - In normal rats, hypoglycemic doses of intravenous insulin bring about glucoprivic
      feeding but the same doses of insulin inhibit feeding when combined with doses of
      glucose that prevent hypoglycemia. In this study, these effects were compared
      between obese Zucker rats (fa-fa), known to present several abnormalities related
      to insulin, and normal Wistar rats by infusion of insulin (1 IU over 1 h),
      insulin plus glucose (5.1 g over 2 h) or vehicle. Feeding patterns and
      microstructure were automatically monitored. Contrary to its effect in the normal
      rats, insulin infusion did not enhance feeding in the Zucker rats but rather
      slightly decreased total food intake and meal duration. The insulin plus glucose
      infusion produced a total anorexia in normal rats but only a partial reduction in
      total food intake and meal duration was observed in Zucker rats. The impaired
      feeding effect of insulin in the Zucker rat may be related to its peripheral
      resistance to insulin which prevents a severe hypoglycemia and therefore
      glucoprivic feeding. The lack of inhibition of feeding when both insulin and
      glucose are infused may account for the well-known delayed satiation and large
      meals in the Zucker rats, possibly involving impaired hypothalamic action of
      insulin.

PMID- 7726541
TI  - Development of altered taste preferences in tumor-bearing rats.
AB  - Experimental tumors induce a decline in food intake that may derive from changes
      in taste or the development of taste aversions. The preferences of tumor-bearing
      (TB) and non-tumor-bearing (NTB) rats for five chemicals (three palatable and two
      aversive taste stimuli) were studied in an animal model of experimental cancer
      employing the methylcholanthrene (MCA) sarcoma. In protocol 1, five groups of
      Fischer 344 rats were given 23-h, two-bottle preference tests (taste solution vs.
      water) daily from day 3 after tumor implantation until spontaneous death
      occurred. Both NTB and TB rats avoided quinine hydrochloride and hydrochloric
      acid solutions throughout the experiment indicating that tumor growth produced no
      disruption in the animals' perception of these normally aversive tastes. In both
      groups, preference for sucrose (88% to 97%) and saccharin (75% to 93%) remained
      high until days 22 and 17 respectively, but tended to decline with advanced tumor
      growth. In both cases, a reduction in total calorie intake preceded the changes
      in sucrose or saccharin preference by several days. With or without a tumor, rats
      exhibited approximately 50% preference for NaCl at all times. In protocol 2, a
      four-bottle preference test (sucrose vs. saccharin vs. NaCl vs. water) was
      administered before tumor implantation and again 3 weeks later when a decline in
      food intake was evident. Both TB and NTB rats displayed a dominant preference for
      sucrose over saccharin, NaCl, and water at the pre- and posttests. However, a
      comparison of the difference scores (pre- minus postimplantation) of NTB and TB
      rats showed a small but significant suppression of TB animals' preference for
      sucrose. The altered preferences for sweet but not salt taste stimuli suggest
      that food-related taste cues may be more susceptible to the development of taste
      aversions during cancer. However the contribution of taste changes to the
      anorexia of cancer remains unclear and it is possible that the changes in taste
      preference may be secondary to the reduction in food intake.

PMID- 7726542
TI  - Role of sensory and cognitive information in the enhancement of certainty and
      liking for novel and familiar foods.
AB  - Expected and actual liking for novel and familiar foods were examined under
      various conditions of sensory and verbal information with 121 subjects who
      differed in food neophobia. The possible mediating roles of uncertainty about
      product identity and resemblance to familiar foods were also investigated.
      Subjects were divided into three verbal information groups (no information;
      product name; ingredient and use information) balanced for neophobia, age and
      gender. All groups rated test samples under three sensory conditions: (1)
      appearance only, (2) appearance and smell and (3) appearance, smell and taste.
      Neophilics rated novel foods more favorably than did neophobics. Accumulating
      sensory experience (appearance, smell, taste) decreased liking for novel foods
      but increased liking for familiar foods. Verbal information generally increased
      liking for all samples. Liking and certainty of product identity were
      curvilinearly related for novel foods, but linearly related for familiar foods.
      Liking for products judged to closely resemble the test product predicted up to
      64% of the variability in expected and actual liking. Eight weeks later, subjects
      rated one of the two novel foods higher than in the first exposure, but no other
      exposure effects were observed. Our data suggest that information (possibly via
      reduced uncertainty), resemblance to more familiar foods, and exposure contribute
      to reducing initially negative responses to novel foods; furthermore, neophobia
      decreases liking for novel foods similarly at all levels of sensory input
      (visual, smell and taste).

PMID- 7726543
TI  - Antecedents and consequences of expectations related to fat-free and regular-fat
      foods.
AB  - Hedonic and sensory expectations related to fat-free and regular-fat pound cake,
      crackers and American cheese were studied with 97 subjects divided into three
      subgroups, each testing one type of product. Four study phases were separated by
      1-month intervals: (1) a questionnaire on demographics, dietary practices and
      consumption of the test products, (2) intensity ratings of sensory attributes and
      ratings of liking of unlabeled fat-free and regular-fat samples, (3) ratings of
      expected attribute intensities and liking in response to product labels of "fat
      free" and "regular", and subsequent ratings of these samples and (4) phase 3
      repeated with opposite (incorrect) labels. Fat-free products were expected to be
      less liked than their regular counterparts; however, only cheese was less liked
      in actual taste tests. Expected liking was best predicted by familiarity with the
      product and, in the case of fat-free products, by the extent to which a person
      substituted low-fat for high-fat foods. Actual liking was best predicted by the
      effect of labeling and by expectations. The expected intensities of sensory
      attributes were uniformly higher in regular than in fat-free products. Both
      sensory and hedonic ratings of labeled samples changed in the direction of
      expectations, as compared to baseline values, supporting an assimilation model of
      the effect of disconfirmed expectations on sensory perception and consumer
      acceptance.

PMID- 7726544
TI  - Exposure to milk or water at preschool lunch for 3 months influences children's
      choice of elementary school lunch drink 4 months later.
AB  - The purpose was to study if serving milk or water with the lunch at preschool
      influenced 6- to 7-year-old children's preferences for and later choice between
      milk and water at lunch in elementary school later. Children (n = 147) at 12
      daycare centres were usually served water at lunch but, for 3 months, six
      randomly chosen centres served milk at lunch (Intervention group) and six matched
      centres continued serving water (Control group). The groups did not differ with
      respect to preferences for seven types of beverages (including water and four
      varieties of milk) either before or after the intervention. Four and 12 months
      later, their choice of lunch drink (milk or water) at school was studied for two
      5-week periods. At the 4-month assessment, the children in the Intervention group
      chose milk at lunch significantly more often than did those in the Control group
      (92% vs. 81% of the days), while there were no significant differences at 12
      months (85% vs. 81%). Since there were no demonstrable effects on preferences,
      one interpretation of the results is that children tend to associate the type of
      drink regularly served at a meal with that specific meal.

PMID- 7726545
TI  - Beauty is in the eye of the beholder: media influences on the psychopathology of
      eating problems.

PMID- 7726546
TI  - Food fads during pregnancy: a question of taste?

PMID- 7726547
TI  - Menstrual cycle effects on mood, eating and food choice.

PMID- 7726548
TI  - Barriers to healthy eating: an examination of perceived behavioural control and
      unrealistic optimism.

PMID- 7726549
TI  - Life in unusual environments: progress in understanding the structure and
      function of enzymes from extreme halophilic bacteria.
AB  - Extreme halophilic archaea are saturated with salt and the intracellular
      electrolyte concentration exceeds that of the extracellular environment. Enzymes
      and other proteins from extreme halophilic archaea have been purified for many
      years and studied by biochemical and biophysical solution methodologies. They are
      active and stable at multimolar salt concentrations and denature below 2 to 3 M
      NaCl or KCl. Adaptation to these high concentrations of salt, genetic and
      evolutionary aspects, and the possibility of biotechnological applications are
      problems of considerable interest. Since the status of this fascinating field of
      research was reviewed in 1992, malate dehydrogenase from Haloarcula marismortui,
      now known to be a tetramer, was sequenced, its gene was cloned and expressed in
      active form, and its physical properties were redefined. A single mutation of
      Arg100 (in the enzyme active site) to Gln switched the enzyme specificity from
      malate to lactate dehydrogenase. Recent determination of its molecular structure
      by X-ray crystallography (O. Dym et al., in press) provides an exciting basis for
      the understanding of the structure and function of extreme halophilic enzymes. A
      major problem which so far has not been tackled in the study of extreme
      halophilic archaea is the understanding of protein nucleic acid interactions
      which are essential for the performance of biological function. Whereas the
      stability and activity of enzymes and other proteins can be modified to perform
      at high salt concentrations by use of currently known structural concepts, the
      existence of meaningful protein nucleic acid interactions in physiological
      concentrations of 4 to 5 M KCl constitutes an unsolved enigma worth intensive
      investigation.

PMID- 7726550
TI  - Purification and characterization of an acyclic monoterpene primary alcohol:NADP+
      oxidoreductase from catmint (Nepeta racemosa).
AB  - A soluble monoterpene primary alcohol:NADP+ oxidoreductase has been purified to
      apparent homogeneity from leaves of the catmint, Nepeta racemosa. The purified
      enzyme consisted of two polypeptides, with molecular masses of 42,000 and 40,000
      Da, and contained zinc ions. A number of monoterpene alcohols (geraniol, nerol,
      citronellol, and their hydroxylated derivatives) were substrates, but the enzyme
      was inactive toward ethanol. The enzyme required NADP(H) as cofactor, with NAD(H)
      ineffective. Gas chromatographic and coupled mass spectrometric analysis of the
      reaction products showed that 10-hydroxygeraniol and 10-hydroxynerol were
      oxidized by the enzyme in the presence of NADP+, at both C-1 and C-10. These
      results are consistent with a role for this enzyme in the biosynthesis of iridoid
      monoterpenes.

PMID- 7726552
TI  - Interference with protein kinase C-related signal transduction in vascular smooth
      muscle cells by benzo[a]pyrene.
AB  - Elucidation of the mechanisms involved in the deregulation of vascular smooth
      muscle cell (SMC) growth and differentiation during the course of atherogenesis
      and the putative role of toxic injury in this process have been a subject of
      considerable interest in recent years. In this regard, we have recently shown
      that in vitro exposure of vascular (aortic) SMCs to benzo[a]pyrene (BaP), an
      atherogenic polycyclic aromatic hydrocarbon, initially delays cell cycle
      progression and inhibits cell proliferation and then causes permanent modulation
      to a highly proliferative state. To define the molecular basis of this response,
      we have examined critical components of the protein kinase C (PKC) signal
      transduction system upon exposure to BaP. Marked inhibition of serum-stimulated
      inositol phospholipid turnover was observed in growth-arrested SMC cultures
      challenged with 30 microM BaP for 24 h and then stimulated with 10% fetal bovine
      serum for 120 or 1800 s. Benzo[a]pyrene inhibited PKC-mediated phosphorylation of
      exogenous and endogenous proteins in the cytosolic and particulate fraction of
      cycling, as well as quiescent cultures. The PKC inhibitory response was observed
      as early as 0.5 h following BaP treatment and maintained for at least 5 days.
      Exposure of quiescent SMCs to 30 microM BaP inhibited the ability of serum to
      induce c-fos mRNA expression and decreased AP-1 binding to a 12-O-tetradecanoyl
      phorbol-13-acetate responsive element. Inhibition of PKC-related signal
      transduction was not due to generalized interference with cell cycle events since
      peak expression of the c-myc and c-Ha-ras protooncogenes following serum
      stimulation of quiescent cultures was unchanged, or slightly enhanced, by 30
      microM BaP. Collectively, these data suggest that the ability of BaP to modulate
      growth and differentiation programs in vascular SMCs involves early interference
      with PKC-related mitogenic signal transduction.

PMID- 7726551
TI  - Farnesylation and proteolysis are sequential, but distinct steps in the CaaX box
      modification pathway.
AB  - Membrane localization of Ras proteins requires posttranslational modification of
      a conserved C-terminal sequence motif known as the CaaX box (C is Cys, a is any
      aliphatic amino acid, and X is the carboxyl terminal residue). The modification
      steps include farnesylation, removal of the three C-terminal amino acids,
      carboxyl-methylation, and palmitoylation. In yeast, the farnesyltransferase
      (FTase) is encoded by the RAM1(DPR1) and RAM2 genes, and the methyltransferase is
      the product of STE14. The gene encoding the protease(s) that is responsible for
      modification of the CaaX has not been identified. We have used in vitro
      synthesized Ras2p and synthetic peptide substrates to investigate the
      relationship between farnesylation and proteolysis. Addition of yeast cytosolic
      extracts to rabbit reticulocyte extracts programmed to synthesize Ras2p led to
      prenylation of Ras2p and a change in electrophoretic mobility similar to that
      observed during Ras maturation in vivo. However, it was not possible to determine
      if the mobility shift is the result of prenylation, proteolysis or a combination
      of both steps. Therefore, we examined the relationship between farnesylation and
      proteolysis directly using extracts prepared from bacteria overexpressing the
      genes for the yeast FTase (RAM1 and RAM2) and synthetic CaaX box peptides.
      Extracts from bacteria expressing RAM1/RAM2 efficiently prenylate CaaX box
      peptides, but do not proteolyze the -aaX residues. However, addition of yeast
      extracts from wild type, ram1, or ste14 mutants resulted in the removal of the 
      aaX residues from prenylated CaaX box peptides.

PMID- 7726553
TI  - P450scc-dependent cholesterol metabolism in rat adrenal mitochondria is inhibited
      by low concentrations of matrix Ca2+.
AB  - Pregnenolone formation at P450scc in isolated rat adrenal mitochondria is
      determined equally by the amount of ACTH-stimulated reactive inner membrane
      cholesterol and by the matrix generation of NADPH. Evidence is presented here
      that both are sensitive to an increase in matrix Ca2+ produced by low levels of
      external Ca2+ (0.4-4 microM). Cholesterol availability to P450scc and
      intramitochondrial NADPH are shown to be highly interdependent. The proportion of
      mitochondrial cholesterol which is readily available to P450scc in the intact
      mitochondria increases as conditions become more favorable for NADPH generation.
      Preincubation of mitochondria without reductant causes substantial decreases in
      cholesterol metabolism when weaker reducing conditions are used without effect on
      NADPH generation as evidenced by unchanged metabolism of 20 alpha
      hydroxycholesterol at P450scc or DOC at P450(11) beta. Increased Ca2+free not
      only increases this sensitivity to preincubation but also inhibits reductant
      transfer from succinate and isocitrate to both P450scc and P450(11) beta.
      Succinate activity was inhibited much more than that of isocitrate. These actions
      of Ca2+, which quantitatively explain the stimulatory characteristics of EGTA in
      standard media, were reversible providing exposure was short (< or = 3 min).
      Ruthenium red (inhibits Ca2+ uptake antiporter) is as effective as EGTA in
      preventing all these effects of Ca2+ while cyclosporin A (prevents opening of
      Ca(2+)-activated inner membrane channels) is partially effective. Ca2+ entry into
      the matrix is, therefore a necessary step prior to inhibition of cholesterol
      metabolism by several mechanisms, including the consequences of changes in inner
      membrane permeability.

PMID- 7726554
TI  - Characterization of a novel alpha-tocopherol-binding protein from bovine heart
      cytosol.
AB  - We previously reported the identification of a new alpha-tocopherol-binding
      protein (approximately 15 kDa) in the cytosol of rat liver and heart and in
      rabbit heart (A.K. Dutta-Roy et al., J. Nutr. Biochem. 5, 562-570, 1994). This
      protein specifically binds alpha-tocopherol and enhances its transfer between
      separate membranes. In the present paper we have purified and characterized the
      alpha-tocopherol-binding protein from bovine heart cytosol and compared its
      various structural and functional properties with the similar size (approximately
      15 kDa) cytosolic fatty acid-binding protein of this tissue. alpha-Tocopherol
      binding protein was purified to electrophoretic homogeneity from bovine heart
      cytosol by a procedure involving precipitation with 70% ammonium sulfate,
      followed sequentially by gel filtration chromatography and chromatofocusing. The
      purified protein migrated as a single band on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis with an apparent molecular mass of 16 kDa.
      Isoelectric focusing of the purified protein showed that the pI value is around
      4.5. The binding of alpha-tocopherol to the purified protein was rapid,
      reversible, and saturable. The alpha-tocopherol-binding protein did not bind
      oleate as assessed by direct radiolabeled fatty acid binding and fluorescence
      enhancement assay. Amino acid analysis showed the presence of a large number of
      Ala, Gly, Ser, Lys, and Pro residues and a lesser number of aromatic residues in
      this protein. Anti-bovine heart fatty acid-binding protein antibody did not
      recognize the alpha-tocopherol-binding protein in the Western blot. The Western
      blot, ligand affinity, molecular size, and amino acid analysis data suggest that
      the alpha-tocopherol-binding protein is different from the cytosolic fatty acid
      binding protein and that it may be involved in intracellular transport and
      metabolism of alpha-tocopherol.

PMID- 7726557
TI  - The long amino-terminal tail domain of annexin XI is necessary for its nuclear
      localization.
AB  - Annexin XI is a newly identified annexin which localizes mainly in the nucleus of
      rat embryonic fibroblasts. There are no typical nuclear localization signals
      (NLS) in the molecule. To define the region responsible for its nuclear
      localization, a series of mutants and chimeric cDNA were constructed. These were
      transiently expressed in COS-7 cells, and the subcellular distributions of the
      mutants and chimeric proteins were determined by indirect immunofluorescence
      microscopy. Wild-type annexin XI was located predominantly within the nucleus.
      Deletion of the N-terminal tail domain (residues 3-196) changed the distribution
      of the protein from the nucleus to the cytoplasm whereas deletion of the C
      terminal core domain (residues 208-504) still kept the protein sorting to the
      nucleus. Three other mutants lacking 60-80 amino acids in the N-terminal region
      (residues 3-61, 61-115, and 115-197, respectively) no longer efficiently imported
      into the nucleus. Furthermore, Escherichia coli beta-galactosidase polypeptide
      was efficiently localized to the nucleus only when fused with the whole N
      terminal region of annexin XI (residues 1-207), not with part of the N-terminal
      region. In primary cultured rat hepatocytes, annexin XI was distributed in the
      cytoplasm but not in the nucleus. These results suggest that the whole N-terminal
      tail domain of annexin XI is necessary and sufficient for its nuclear
      localization, and may function as NLS in a cell-type specific manner.

PMID- 7726555
TI  - Fatty acids promote the formation of complexes between choline-phosphate
      cytidylyltransferase and cytidylyltransferase binding protein.
AB  - We previously identified a 112-kDa protein (CTBP) that binds CTP:choline
      phosphate cytidylyltransferase (CT) (D.A. Feldman and P.A. Weinhold, 1993, J.
      Biol. Chem. 268, 3127-3135). In this study we show that fatty acids promote the
      binding of cytidylyltransferase to CTBP. Gel filtration chromatography separated
      CTBP from CT in liver cytosol. CTBP was eluted slightly slower than the
      thyroglobulin standard. The addition of oleate to cytosol followed by incubation
      at 37 degrees C resulted in the formation of aggregates containing both CT and
      CTBP. The aggregates eluted in the void volume of the gel filtration column,
      sedimented to the bottom of glycerol density gradients, and precipitated at
      concentrations of polyethylene glycol lower than required to precipitate CT and
      CTBP in untreated cytosol. Immunoprecipitation by CT antibodies of both CT and
      CTBP in aggregate preparations provided further evidence for the formation of CT
      CTBP complexes. A smaller CT-CTBP complex was isolated by glycerol density
      centrifugation from cytosol incubated with oleate at 4 degrees C. Overall, these
      results suggest that oleate promotes the binding of CT to CTBP. The results
      suggest that a dissociable complex is formed at 4 degrees C in the presence of
      oleate which is polymerized by incubation at 37 degrees C to a large aggregate
      that is more resistant to dissociation. Complex formation at 37 and 4 degrees C
      was dose dependent at oleate concentrations between 50 and 200 microM. Complex
      formation at 4 degrees C was specifically promoted by long-chain, unsaturated
      fatty acids. These results suggest that CTBP may be involved in the fatty acid
      induced translocation of cytidylyltransferase.

PMID- 7726558
TI  - Ah receptor phosphorylation: localization of phosphorylation sites to the C
      terminal half of the protein.
AB  - The aryl hydrocarbon receptor (AhR) is a transcriptional enhancer activated by
      the binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related
      xenobiotics. Ligand binding initiates a series of poorly understood molecular
      events which confers recognition of cis-acting elements located in regulatory
      regions of particular structural genes, such as CYP1A1. Several studies have
      suggested that AhR phosphorylation may be instrumental in activating the AhR to a
      DNA-binding state. In agreement with previous investigations, treatment of the
      AhR with acid phosphatase resulted in the loss of DNA-binding activity. To
      further evaluate the functional role of AhR phosphorylation we determined whether
      TCDD binding altered total AhR phosphorylation, and identified phosphorylated
      regions by the examination of chemical cleavage patterns. The AhR was isolated by
      immunoprecipitation from [32P]-orthophosphate-labeled Hepa 1 cells grown in the
      presence or absence of TCDD. Examination of the amount of 32P associated with the
      AhR indicated that the total level of AhR phosphorylation was not affected by
      ligand binding. Chemical cleavage with hydroxylamine and cyanogen bromide also
      revealed a similar pattern for liganded and unliganded AhR. The shortest regions
      of overlap determined by the chemical cleavage patterns localized phosphorylation
      sites to two regions in the C-terminal half of the AhR. One region is centrally
      located between amino acids 368 and 605 and within or adjacent to a DNA binding
      repressor domain. The other region is located at the glutamine-rich carboxyl
      terminus between amino acids 636 and 759. These data coupled with previous
      observations imply that total AhR phosphorylation is not altered by the ligand
      elicited transformation to a DNA-binding form, but that phosphorylation
      nevertheless plays an important role in the ability of an active AhR-Arnt complex
      to associate with cis-acting regulatory elements.

PMID- 7726556
TI  - The multicatalytic proteinase (proteasome) of the hawkmoth, Manduca sexta:
      catalytic properties and immunological comparison with the lobster enzyme
      complex.
AB  - The proteasome plays a central role in ubiquitin-dependent and -independent
      proteolysis in eukaryotic cells. The hawkmoth proteasome was purified from larval
      body wall and characterized with respect to substrate specificity, sensitivity to
      protease inhibitors, and cross-reactivity with monoclonal antibodies (mAbs)
      raised against human placenta proteasome. Leupeptin selectively inhibited the
      trypsin-like activity (T-L) and N-ethylmaleimide inhibited both T-L and
      chymotrypsin-like activities, whereas 0.02% sodium dodecyl sulfate stimulated the
      peptidylglutamyl peptide hydrolase, branched-chain amino acid preferring, and
      caseinolytic activities 20-, 18-, and 3.8-fold, respectively. All four peptidase
      activities were inhibited by 3,4-dichloroisocoumarin. One-dimensional immunoblot
      analysis showed that the level and subunit composition of the proteasome varied
      between tissues. The relative levels of proteasome were high in intersegmental
      muscle and ovary, lower in Malpighian tubule, male accessory gland, and ventral
      nerve cord, and lowest in flight muscle and fat body. The tissues differed in the
      relative amount of a 41-kDa doublet; a 22-kDa subunit was present only in the
      male accessory gland. Two-dimensional polyacrylamide gel electrophoresis showed
      that the hawkmoth proteasome contained at least 26 subunits, compared with 28
      subunits in lobster. Immunological analysis using four subunit-specific mAbs
      identified the putative homologs of the human zeta, C2, C3, and C8 alpha-type
      subunits in the hawkmoth and lobster enzymes. Two of the four mAbs reacted with
      three or more of the hawkmoth subunits and three of the mAbs reacted with two or
      more of the lobster subunits. In addition, two other mAbs that recognize epitopes
      shared by a number of alpha-type subunits indicated that at least 15 (lobster) or
      16 (hawkmoth) subunits were alpha-type. These results suggest that much of the
      subunit complexity of the arthropod proteasomes is a consequence of extensive
      post-translational modifications.

PMID- 7726560
TI  - Characterization of glycosylphosphatidylinositol (GPI)-anchored NCAM on mouse
      skeletal muscle cell line C2C12: the structure of the GPI glycan and release
      during myogenesis.
AB  - The mouse myoblast cell line C2C12 constitutively expressed 160-kDa transmembrane
      NCAM isoform and 135-kDa GPI-anchored isoform before differentiation. During
      differentiation into multinucleated myotubes, the cells newly expressed 150-kDa
      GPI-anchored isoform and the level of 135-kDa GPI-anchored isoform increased.
      Structural analysis of the GPI glycan of NCAM, which was purified from C2C12
      myotubes after metabolic labeling with [3H]inositol, was performed by sequential
      exoglycosidase digestion and Wistaria floribunda agglutinin-agarose column
      chromatography. The core GPI glycan structure, Man alpha 1-2Man alpha-Man alpha
      GlcNH2-myoInositol, was conserved and variations were observed in additional
      mannose and N-acetylgalactosamine residues. Structural analysis of the GPI
      glycans of the two GPI-anchored isoforms, GPI-NCAM 135 and GPI-NCAM 150, showed
      the enhanced attachment of the N-acetylgalactosamine residue to the GPI glycan
      core of GPI-NCAM 150. These GPI-anchored NCAM isoforms were released from C2C12
      cells during the myoblast differentiation. Release of GPI-anchored NCAMs was
      observed when C2C12 cells were cultured in a serum-free medium, and inositol but
      not inositol phosphate was detected after nitrous acid deamination of the
      released NCAM. These results suggest that the GPI-anchored NCAM was released from
      the cell surface by the action of an endogeneous phospholipase D.

PMID- 7726559
TI  - Dexamethasone induces resistance to the lethal consequences of electron transport
      inhibition in cultured hepatocytes.
AB  - Pretreatment of cultured rat hepatocytes with 1 microM dexamethasone protected
      against cell killing by 5 microM rotenone and 1 mM cyanide. Simultaneous
      treatment (no pretreatment) was ineffective, as was pretreatment with 10 microM
      of sex hormones or the mineralocorticoid aldosterone. Protection by dexamethasone
      was blocked by 10 microM of glucocorticoid receptor antagonist, RU486, and by 1
      microM of the inhibitor of protein synthesis, cycloheximide. Cells pretreated
      with dexamethasone for 6, 12, and 18 h showed increasing degrees of protection.
      Pretreatment with dexamethasone had no effect on either the decline of cellular
      ATP or the loss of the mitochondrial membrane potential. In addition,
      dexamethasone did not prevent the mitochondrial permeability transition. By
      contrast, dexamethasone prevented the increased release of [3H]arachidonic acid
      from phospholipids produced by cyanide. These data describe an inductive effect
      of dexamethasone in protecting cultured hepatocytes against inhibition of
      electron transport by rotenone and cyanide. It is concluded that pretreatment
      with dexamethasone prevents cell killing by inhibiting a mechanism that couples
      the mitochondrial permeability transition to the accelerated degradation of
      plasma membrane phospholipids.

PMID- 7726561
TI  - Metabolism of fructose-3-phosphate in the diabetic rat lens.
AB  - Fructose-3-phosphate and sorbitol-3-phosphate are produced in diabetic rat lenses
      by a 3-phosphokinase. While sorbitol-3-phosphate appears to be an inert polyol
      phosphate, fructose-3-phosphate is a potent cross-linking agent and a potential
      in vivo source of 3-deoxyglucosone. The objective of this study was to
      investigate the production and decomposition of fructose-3-phosphate in the
      diabetic rat lens. The results indicate that this metabolite achieves a steady
      state concentration of almost 1 mumol/g wet weight within 2 weeks after the onset
      of diabetes. These steady-state levels appear to be a consequence of a balance
      between its production from fructose and its further decomposition to 3
      deoxyglucosone. This conclusion is supported by results from disappearance of
      fructose-3-phosphate in insulin-treated diabetic rats and in vitro incubations of
      fructose-3-phosphate with amines where production of 3-deoxyglucosone was
      detected using a number of different methods including mass spectrometry. In
      agreement with these results, elevated concentrations of 3-deoxyglucosone along
      with its detoxification product, 3-deoxyfructose, were detected in the diabetic
      rat lenses. Other sugars and sugar phosphates which were detectable in the
      diabetic rat lenses were glucose, fructose, glucose-6-phosphate, fructose-6
      phosphate, and sedoheptulose-7-phosphate. In conclusion, results from this study
      suggest that fructose-3-phosphate and 3-deoxyglucosone are likely to be important
      contributors to the process of nonenzymatic glycation in diabetic rat lenses.

PMID- 7726562
TI  - DBHBM (3,5-dibromo-4-hydroxy-benzylidenemalonitrile) is a novel inhibitor of
      electron transfer through the QN center of the mitochondrial bc1 complex.
AB  - DBHBM (3,5-dibromo-4-hydroxy-benzylidenemalonitrile) inhibited the NADH- or
      succinate-supported rate of O2 consumption in beef heart submitochondrial
      particles (Ki = 7 x 10(-7) M). Oxygen comsumption was restored with the addition
      of ascorbate/TMPD, indicating that the inhibitory effect was on the ubiquinol
      cytochrome c reductase activity of the respiratory chain. Difference spectra with
      submitochondrial particles indicated that DBHBM blocked electron transport
      through the cytochrome bc1 complex, in a mode closely similar to that of
      antimycin A. The reduction rates of cytochrome b by succinate were strongly
      inhibited in the presence of DBHBM plus myxothiazol, but not by DBHBM plus
      antimycin A. These data suggest that DBHBM may bind primarily to the QN center.
      In the purified bc1 complex, DBHBM and antimycin A induced a red shift from 562
      to 566 nm of the alpha peak of cytochrome b, supporting the idea that DBHBM
      influences predominantly the ligand field of the b562 (bh) heme. Difference
      spectra in the presence or absence of myxothiazol showed that DBHBM induced the
      same red shift with a maximum at 565 nm and a minimum at 559 nm. We conclude that
      DBHBM blocks electron transfer at the QN center and thus may be considered a
      novel group III inhibitor of the bc1 complex.

PMID- 7726563
TI  - Thermally induced unfolding of Acanthamoeba myosin II and skeletal muscle myosin:
      nucleotide effects.
AB  - The thermal unfolding of monomeric Acanthamoeba myosin II and rabbit skeletal
      muscle myosin at pH 7.5 in 0.6 M KCl has been studied by differential scanning
      calorimetry (DSC) and circular dichroism. A single endotherm (at approximately 40
      to 45 degrees C) with a maximum at 41.7 +/- 0.1 degrees C and delta H
      approximately 1080 +/- kcal/mol is observed for both dephospho- and phospho
      myosin II. Skeletal muscle myosin unfolds with less cooperativity over a wider
      temperature range (approximately 40 to 60 degrees C) with delta H approximately
      2500 kcal/mol. The thermal unfolding of either myosin results in a loss of
      approximately 70% of alpha-helical structures. Saturation of dephospho- or
      phospho-myosin II with 5'-adenylylimidodiphosphate (AMPPNP) in the presence of
      Mg2+ produces a second endotherm with a maximum at approximately 49 degrees C.
      The latter observation is attributed to a stabilization of head regions by
      nucleotide binding. Indeed, a purified N-terminal myosin II head fragment has
      been found to unfold with Tmax approximately 41 and approximately 48 degrees C in
      the absence and presence of AMPPNP, respectively. The stabilization of the head
      regions is less with ADP+Pi and still smaller with ADP alone. In summary,
      thermally induced unfolding of myosin II is affected by nucleotide binding to
      heads, but not by phosphorylation or even removal of a 66-amino-acid tailpiece
      containing phosphorylation sites. The observed differences in the cooperativity
      of unfolding myosin II and skeletal muscle myosin relate to differences between
      rod structures and possibly also head-rod interactions.

PMID- 7726564
TI  - Modulation of ADP-stimulated inositol phosphate metabolism in rat alveolar
      macrophages by oxidative stress.
AB  - The present study examined alterations of adenosine-5-diphosphate (ADP)
      stimulated inositol phosphate (IP3) metabolism and the respiratory burst of rat
      alveolar macrophages (AM) under oxidant stress using the model oxidant, tert
      butyl hydroperoxide (tBOOH). Isolated AM were maintained in a system with an air
      liquid interface, which approximates the lung environment. tBOOH produced a dual
      effect on the ADP-stimulated respiratory burst of these AM. Pretreatment of these
      AM with 50 microM tBOOH for 15 min led to a significant enhancement of the
      respiratory burst while significant inhibition was observed with 200 microM
      tBOOH. Treatment of AM with 100 microM ADP led to a significant increase in the
      generation of IP3, reaching a maximum at 30 s. In contrast, treatment of AM with
      50 or 200 microM tBOOH did not stimulate IP3 generation during a 15-min period.
      Pretreatment of AM with 50 microM tBOOH for 15 min had no effect on ADP
      stimulated IP3 generation. Preincubation with 200 microM tBOOH significantly
      inhibited generation of IP3 in response to ADP stimulation; however, this
      probably did not contribute to inhibition of the respiratory burst. The results
      suggest that production of IP3 may participate in stimulation of the respiratory
      burst by ADP but that enhancement of the respiratory burst by 50 microM tBOOH
      probably did not involve alteration of IP3 production.

PMID- 7726565
TI  - Modification of chloride ion transport in human erythrocyte ghost membranes by
      photoaffinity labeling reagents based on the structure of 5-nitro-2-(3
      phenylpropylamino)-benzoic acid (NPPB).
AB  - Using human red blood cell ghost membranes, we have evaluated 5-nitro-2-[N-3-(4
      azidophenyl)-propylamino]-benzoic acid and 5-nitro-2-[N-3-(4-azido-2,3,5,6
      tetrafluorophenyl)-propylamino]- benzoic acid (FAzNPPB) as photoaffinity labeling
      agents based on the structure of the widely important Cl- channel blocker 5-nitro
      2-(3-phenylpropyl-amino)-benzoic acid (NPPB). The tetrafluoro-substituted aryl
      azide was found to be a more effective photoinactivating agent than the
      corresponding protio compound. Using a tritiated version ([3H]FAzNPPB), we
      demonstrated that photoinactivation of Cl- flux was accompanied by photolabeling
      of the band 3 protein and membrane lipids. Both processes were diminished in the
      presence of NPPB and the related arylanthranilate flufenamic acid. Photolabeling
      resulted in the incorporation of 1.0 +/- 0.2 mol 3H/mol protein in the band 3
      integral membrane domain, whereas the cytoplasmic domain was essentially
      unlabeled. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      photolabeling was found to be the result of partial labeling of at least three
      different regions of the membrane domain. Based on trypsin proteolysis, reverse
      phase high-performance liquid chromatography and electrospray ionization mass
      spectrometry analysis, it is proposed that one of the sites of photolabeling is
      the peptide lys-phe-lys (590-592). FAzNPPB is a successful polyfluoro aryl azide
      photoaffinity labeling agent which may be of further use in studying the diverse
      effects of arylanthranilates on biological membranes.

PMID- 7726567
TI  - Tocopherols and 6-hydroxy-chroman-2-carbonitrile derivatives inhibit vascular
      smooth muscle cell proliferation by a nonantioxidant mechanism.
AB  - The effects of two groups of similar compounds, a series of tocopherols and one
      of 6-hydroxy-chroman-2-carbonitrile, have been studied in vascular smooth muscle
      cells. A poor correlation has been found between antiproliferative and
      antioxidant properties of these molecules. D-alpha-Tocopherol inhibits cell
      proliferation, while D-alpha-tocopherylquinone has been found neither to inhibit
      nor to activate. D-beta-Tocopherol, a poor inhibitor of smooth muscle cell
      proliferation, has been shown to be capable of preventing and reversing the
      inhibition by D-alpha-tocopherol. It is concluded that the tocopherols and
      carbonitrile derivatives tested here appear to inhibit smooth muscle cell
      proliferation by a nonantioxidant mechanism. The competition between D-alpha
      tocopherol and D-beta-tocopherol suggests the existence of a common binding site
      for the two molecules.

PMID- 7726566
TI  - Transient adaptation of oxidative stress in mammalian cells.
AB  - We report a transient adaptation to the oxidative stress of hydrogen peroxide
      (H2O2) exposure in several mammalian cell lines: Chinese hamster ovary fibroblast
      (CHO) cells, HA-1 cells (a defined CHO subclone), C3H 10T1/2 cells (embryonic
      mouse fibroblasts), V79 cells (Chinese hamster lung fibroblasts), and Clone 9
      liver cells (rat liver epithelial cells). Up to 40-fold adaptive increases in
      resistance to H2O2 challenge occurred following pretreatment with relatively low
      H2O2 "priming" doses, from as little as 1.9% cell viability for untreated cells
      to as much as 76.5% viability for H2O2 pretreated cells. Detailed studies with HA
      1 cells revealed the following pattern of responses to H2O2: very low H2O2
      concentrations of 0.1 to 0.5 mumol/10(7) cells (3 to 15 microM) stimulated cell
      growth by 25 to 45%; low H2O2 concentrations of 2-5 mumol/10(7) cells (120 to 150
      microM) induced a temporary growth-arrest, a lengthening of cell cycle from 18 h
      to approximately 26 h, and marked adaptive increases in H2O2 resistance;
      intermediate H2O2 concentrations of 9 to 14 mumol/10(7) cells (250 to 400 microM)
      caused permanent growth-arrest (i.e., permanent loss of replicative or divisional
      competence) with no evidence of necrosis; high H2O2 concentrations of 30
      mumol/10(7) cells or greater (> or = 1 mM) caused an apoptotic-like necrotic cell
      death and destruction. The adaptive response to low H2O2 concentrations of 2-5
      mumol/10(7) (120 to 150 microM) was maximal 18 h after pretreatment of HA-1
      cells, declined thereafter toward baseline sensitivity, and was observed with
      both 7-day fix and stain procedures and clonogenic viability assays. Transient
      adaptation following H2O2 pretreatment of 4.15 mumol/10(7) (150 microM) involved
      the de novo synthesis of at least 20 proteins and was blocked by the translation
      inhibitor, cycloheximide. During the 18-h adaptation in HA-1 cells proteins were
      synthesized in three phases; early (0-4 h), middle (4-8 h), and late (8-15 h). No
      H2O2 response proteins were synthesized beyond 18 h after pretreatment, by which
      time adaptation had already maximized. Selective translational inhibition of the
      early, middle, or late proteins revealed that all three sets were necessary for a
      maximal adaptive increase in H2O2 resistance. Northern blot and enzyme activity
      analyses revealed no significant increases in transcription or translation of the
      classical antioxidant enzymes catalase, glutathione peroxidase, phospholipid
      hydroperoxide glutathione peroxidase, Cu, Zn superoxide dismutase, or Mn
      superoxide dismutase in H2O2-adapted HA-1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7726568
TI  - On the mechanism of interaction of steroids with human glucose 6-phosphate
      dehydrogenase.
AB  - Previous studies have demonstrated that certain 17- and 20-ketosteroids are
      potent inhibitors of the NADP-linked oxidation of glucose 6-phosphate by
      mammalian glucose 6-phosphate dehydrogenases. This inhibition is uncompetitive
      with respect to both NADP+ and glucose 6-phosphate. In order to elucidate the
      detailed mechanism of this rare type of inhibition, we examined the effects of
      steroids on human glucose 6-phosphate dehydrogenase catalyzing the reverse
      reaction, i.e., the reduction of the gluconolactone by NADPH. To circumvent
      problems associated with the known instability of 6-phospho-delta-gluconolactone,
      the natural product of glucose 6-phosphate oxidation, the more stable 6-phospho
      gamma-gluconolactone was used. Dehydroepiandrosterone, epiandrosterone, 16 alpha
      bromoepiandrosterone, and dehydroepiandrosterone sulfate all inhibited the
      reverse reaction uncompetitively with respect to both NADPH and the gamma
      lactone. The Ki values for each of these steroids, determined by varying either
      coenzyme or substrate in both the forward and the reverse reactions, are very
      similar. These results demonstrate that steroids inhibit glucose 6-phosphate
      dehydrogenase by binding to the ternary enzyme-coenzyme-substrate ternary
      complex(es). This is the first direct demonstration that uncompetitive inhibition
      of a two-substrate enzyme, by compounds other than its substrates or products,
      can occur by binding of the inhibitor to a ternary enzyme complex.

PMID- 7726569
TI  - Synthesis of glutathione in the preimplantation mouse embryo.
AB  - Depletion and repletion of glutathione in two-cell to blastocyst stage mouse
      embryos was examined. Reduced (GSH) and oxidized glutathione (GSSG) were measured
      by fluorimetric HPLC after derivatization of extracted embryo samples with dansyl
      chloride. Addition of buthionine sulfoximine (BSO) to culture medium for 16 h
      decreased GSH levels in both two-cell and blastocyst stage embryos; however, GSH
      decreased more drastically in blastocysts. Addition of diethyl maleate (DEM) to
      culture medium depleted GSH in both two-cell and blastocyst stage embryos. After
      removal of DEM, GSH levels returned to normal in blastocysts, and addition of BSO
      or removal of cystine from medium blocked GSH repletion. Two-cell stage embryos
      were unable to recover GSH levels after depletion and exhibited decreased in
      vitro development. Addition of methionine to culture medium was unable to
      substitute for cystine as a source of cysteine in glutathione synthesis,
      indicating that the embryos do not use the cystathionine pathway. Embryos
      collected early on Day 3 of development were unable to recover GSH levels within
      5 h, whereas embryos collected late on Day 3 recovered GSH within 5 h. Addition
      of cycloheximide to culture medium at noon on Day 3 of development decreased the
      ability of blastocysts to recover their GSH levels late on Day 3. These data
      indicate that GSH turnover and synthesis increases between the two-cell and
      blastocyst stages. The increase in the ability of embryos to synthesize GSH on
      Day 3 is dependent on protein synthesis. Cleavage stage embryos have limited
      capacity to synthesize GSH and appear susceptible to adverse effects of toxicants
      or conditions that deplete glutathione.

PMID- 7726572
TI  - Evidence for free radical generation due to NADH oxidation by aldehyde oxidase
      during ethanol metabolism.
AB  - Several studies associate ethanol hepatic toxicity to the generation of reactive
      oxygen species. Ethanol metabolism by alcohol dehydrogenase (ADH) originates
      acetaldehyde and NADH, with the subsequent increase of the NADH/NAD+ ratio. Some
      authors have suggested that the oxidation of acetaldehyde by aldehyde oxidase
      (AO) may be responsible for oxyradical generation during ethanol metabolism. In
      this study we demonstrated that AO acts not only upon acetaldehyde but also upon
      NADH, with superoxide anion radical (O2.-) formation. The apparent Km of NADH for
      AO was approximately 28 microM, a much smaller value than the one reported for
      acetaldehyde (1 mM). The NADH oxidation by AO promoted the O2.- generation and
      the ADP-Fe(3+)-dependent microsomal lipid peroxidation in a NADH and AO
      concentration-dependent manner. If in these experiments NADH is substituted by
      ethanol, NAD+, and ADH, a higher level of lipid peroxidation will be obtained. To
      explain this observation a vicious cycle which increases the oxyradical
      production is suggested: ADH reduces NAD+ to NADH, which is oxidized by AO,
      generating reactive oxidative species plus NAD+ available again for reduction by
      ADH. From the studies which were done in the presence of some antioxidants it was
      observed that the addition of SOD and/or catalase did not inhibit lipid
      peroxidation, but these results do not exclude the participation of reactive
      oxygen species. Our studies indicate that the NADH oxidation by AO may play a
      role in ethanol-induced generation of reactive oxygen species, contributing to
      its hepatotoxicity.

PMID- 7726571
TI  - Purification and physicochemical properties of the low-potential cytochrome C549
      from the cyanobacterium Synechocystis sp. PCC 6803.
AB  - A soluble low-potential cytochrome c549 has been purified in milligram quantities
      from the cyanobacterium Synechocystis sp. PCC 6803. The protein exhibits an acid
      isoelectric point of 3.9, a molecular mass of 15.8 kDa, and a midpoint redox
      potential value of -250 mV at pH 7.0 EPR and 1H NMR studies suggest a low-spin
      heme iron with bis-histidine coordination at the fifth and sixth positions. EDTA
      photoreduced 5-deazariboflavin has been used as the electron-donating system to
      study, by laser flash absorption spectroscopy, the electron transfer reactions
      between Synechocystis cytochrome c549 and redox proteins involved in the cyclic
      electron flow around photosystem I. The second-order rate constants (k2) obtained
      for ferredoxin (or flavodoxin) oxidation by Synechocystis cytochrome c549 are
      rather low (ca. 10(5) M-1 s-1), thus suggesting that this low-potential heme
      protein does not operate as the primary electron carrier for either transferring
      electrons to the cytochrome b6f complex in cyclic photophosphorylation or to
      hydrogenase during anaerobic metabolism. The k2 values for plastocyanin reduction
      by cytochrome c549 are about 100 times higher (ca. 10(7) M-1 s-1), but it remains
      to be determined whether or not this reaction actually reflects a physiological
      process.

PMID- 7726570
TI  - Inhibition of interleukin-2/p55 receptor subunit interaction by complementary
      peptides.
AB  - Complementary peptides to interleukin-2 (IL-2) sequences important for receptor
      binding were tested for their ability to mimic natural receptors and act as
      inhibitors of the IL-2/p55 receptor subunit interaction. Peptides hydropathically
      complementary to IL-2 sequences 15-27 and 40-54 were synthesized in a linear and
      in a multimeric form and then characterized first by solid-phase binding assays
      for their ability to interact with IL-2. Binding between the multimeric
      complementary peptides and biotinylated IL-2 was specific, saturable, and
      inhibited by linear as well as multimeric complementary peptides. Saturable
      interactions, characterized by dissociation constants in the micromolar range,
      occurred also between IL-2 immobilized on microtiter plates and biotinylated
      linear and multimeric complementary peptides. Peptides corresponding to the IL-2
      target sequences were able to interfere with this interaction, as well as full
      length IL-2. Peptide recognition was sequence dependent, since scrambling of
      complementary peptide sequences or IL-2 target peptide sequences abolished
      binding. Multimeric complementary peptides after immobilization on solid supports
      proved useful also for affinity purifications of recombinant IL-2 or IL-2
      fragments corresponding to the target sites, directly from crude mixtures, in
      high yield and with high recovery. Complementary peptides to IL-2 sequence 15-27,
      but not to IL-2 sequence 40-54, in the linear or in the multimeric form, even if
      with different potency, interfered with the IL-2/p55 receptor subunit interaction
      in vitro, thus suggesting a possible role of this IL-2 site in receptor
      recognition.

PMID- 7726573
TI  - Characterization of P-S bond hydrolysis in organophosphorothioate pesticides by
      organophosphorus hydrolase.
AB  - The extensive use of organophosphorothioate insecticides in agriculture has
      resulted in the risk of environmental contamination with a variety of broadly
      based neurotoxins that inhibit the acetylcholinesterases of many different animal
      species. Organophosphorus hydrolase (OPH, EC 3.1.8.1) is a broad-spectrum
      phosphotriesterase that is capable of detoxifying a variety of organophosphorus
      neurotoxins by hydrolyzing various phosphorus-ester bonds (P-O, P-F, P-CN, and P
      S) between the phosphorus center and an electrophilic leaving group. OPH is
      capable of hydrolyzing the P-X bond of various organophosphorus compounds at
      quite different catalytic rates: P-O bonds (kcat = 67-5000 s-1), P-F bonds (kcat
      = 0.01-500 s-1), and P-S bonds (kcat = 0.0067 to 167 s-1). P-S bond cleavage was
      readily demonstrated and characterized in these studies by quantifying the
      released free thiol groups using 5,5'-dithio-bis-2-nitrobenzoic acid or by
      monitoring an upfield shift of approximately 31 ppm by 31P NMR. A decrease in the
      toxicity of hydrolyzed products was demonstrated by directly quantifying the loss
      of inhibition of acetylcholinesterase activity. Phosphorothiolate esters, such as
      demeton-S, provided noncompetitive inhibition for paraoxon (a P-O triester)
      hydrolysis, suggesting that the binding of these two different classes of
      substrates was not identical.

PMID- 7726574
TI  - Metabolic regulation of active retinoid concentrations in cultured human
      epidermal keratinocytes by exogenous fatty acids.
AB  - Retinol metabolism was examined in cultured human epidermal keratinocytes
      incubated with medium containing physiological concentrations of bovine serum
      albumin-free fatty acid complexes and [3H]retinol. Unsaturated 16- and 18-carbon
      fatty acids: (1) promoted up to a 50% increase in the steady state total cell
      retinoid mass which was accounted for as retinyl ester corresponding to the added
      fatty acid, (2) decreased the rate of endogenous retinyl ester utilization up to
      80%, (3) decreased the steady state cellular concentrations of retinol, 3,4
      didehydroretinol and their respective carboxylic acids up to 80%, and (4) did not
      alter the rate of retinoic acid metabolism. Increasing the medium retinol
      concentration augmented the fatty acid-stimulated increase in esters and blunted
      the extent of decrease in alcohols and acids. Saturated fatty acids with 14, 16,
      17, and 18 carbons also reduced the rate of retinyl ester utilization and the
      cellular concentrations of the retinoid alcohols and acids but had little to no
      effect on retinyl ester synthesis. The data demonstrate that exogenous fatty
      acids possess the capacity to regulate the cellular concentrations of substrate
      retinoid alcohols, active retinoid acids, and the overall rate of retinol
      metabolism via substrate-mediated stimulation of retinol esterification and
      decreasing retinyl ester utilization. Fatty acids thus possess the potential to
      play a physiological role in modulating retinoid signaling in keratinocytes by
      regulating cellular concentrations of active retinoids.

PMID- 7726575
TI  - Kinetic and pharmacologic characterization of phospholipases A2 from Bothrops
      neuwiedii venom.
AB  - Two phospholipases A2 (PLA2) (EC 3.1.1.4) were purified from Bothrops neuwiedii
      venom (isoenzymes P-1 and P-2). The molecular weights of P-1 and P-2 as estimated
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 15,000 and
      16,200 and the isoelectric points were 4.8 and 4.6, respectively. The N-terminal
      14-amino-acid sequences determined were Asn-Leu-Val-Gln-Phe-Glu-Thr-Leu-Ile-Met
      Met-Ile-Ala-Gly and Ser-Leu-Val-Gln-Phe-Glu-Thr-Leu-Ile-Met-Met-Ile-Ala-Gly for P
      1 and P-2, respectively. Since both show sequence almost identical to that of a
      PLA2 from Crotalus atrox it was tentatively classified as being of group II. The
      enzymatic activity of P-1 and P-2 toward lipid monolayers was studied. The
      hydrolysis of dilauroylphosphatidylcholine (dlPC) shows a broad optimum between 7
      and 18 mN m-1 and a cut-off pressure of 22 mN m-1. The activity toward dlPC
      displays a maximum at pH 8 and is dependent on the presence of Ca2+ with an
      apparent Kd of 0.1 mM, for both enzymes. P-1 and P-2 are heat-stable enzymes,
      unable to hydrolyze dilauroylphosphatidic acid monolayers. The enzymes are not
      lethal to mice at doses up to 5 micrograms/g body weight by intraperitoneal
      injection and they do not show myotoxic (up to 40 micrograms) or hemolytic
      activity (up to 8.5 micrograms/ml). Both lack anti-coagulant activity, determined
      by absence of changes in the recalcification time of platelet poor plasma (up to
      100 micrograms/ml), and are not able to induce platelet aggregation (up to 50
      micrograms/ml). However, both isoenzymes exhibit an important edema-inducing
      activity that is not altered at short times by the irreversible chemical
      inactivation of the hydrolytic activity with phenacyl bromide. P-1 and P-2 are
      able to release arachidonic acid from membrane phospholipids of neutrophils,
      property that is lost by the inactivation of the enzyme. This suggests that the
      edema-inducing activity of the active but not the inactive forms may be partly
      due to arachidonic acid-derived mediators. The edema-inducing activity of the
      active or inactive forms of the enzymes is inhibited by antagonists of histamine,
      suggesting that histamine plays an important role in both the active and the
      inactive B. neuwiedii PLA2s-induced edema. The results suggest that the
      inflammatory and the catalytic activity of these enzymes constitute separate
      properties.

PMID- 7726576
TI  - Transcriptional elements directing a liver-specific expression of P450/6 beta A
      (CYP3A2) gene-encoding testosterone 6 beta-hydroxylase.
AB  - The P450/6 beta A (CYP3A2) gene encoding a testosterone 6 beta-hydroxylase is
      expressed predominantly in liver and induced by the treatment of rats with
      various compounds. To understand the mechanism of the basal transcriptional
      activation of the CYP3A2 gene, the cis-acting elements in the proximal promoter
      region (-165 to -73) of the CYP3A2 gene were identified in this study. Nuclear
      extract from rat livers interacted with three sites, 6 beta A-A (-106 to -87), 6
      beta A-B (-140 to -119) and 6 beta A-C (-163 to -145). These sites were
      detectable by DNase I footprinting and gel mobility shift assays and found to
      share nucleotide sequence similarity with each other
      (T(A/C)(A/C)N(A/G)AAG(G/T)(C/T)CA). Direct repeats of AGTTCA (-134 to -120) and
      AG(G/C)TCA (-162 to -148) are also detected in 6 beta A-B and 6 beta A-C sites,
      respectively. To elucidate the relationship of these sites with basal
      transcriptional activation of the CYP3A2 gene, varying lengths of the proximal
      promoter region (-164 to +41) fused to a CAT reporter gene were transfected in
      human hepatoma (HepG2) and mouse adrenal tumor (Y-1) cells. The relative level of
      CAT activity in HepG2 cells was slightly increased by the deletion of the 5'
      portion from -164 to -111 bp, but was reduced to 14% of the control (the
      construct including from -110 to +41) by the deletion from -110 to -81 including
      the 6 beta A-A site. On the other hand, these deletions have no clear effect on
      the level of the activity in Y-1 cells. Substitution mutations at two nucleotides
      in the 6 beta A-A site resulted in the reduction of CAT activity in HepG2 cells
      to 12% of the activity in the wild-type construct. The interaction of an
      oligonucleotide corresponding to the 6 beta A-A site (-106 to -87) with liver
      nuclear factors was completely inhibited by the addition of a typical
      oligonucleotide for hepatocyte nuclear factor-4 (HNF-4) binding site (F. M.
      Sladek, W. Zhong, E. Lai, and J. E. Darnell, Jr., 1990, Genes Dev. 4, 2353-2365)
      but not of oligonucleotides corresponding to 6 beta A-B or 6 beta A-C sites.
      These results suggest an essential role of the binding of HNF-4 and/or HNF-4
      related nuclear factors to the 6 beta A-A site on the basal transcriptional
      activation of the CYP3A2 gene in liver cells.

PMID- 7726577
TI  - Isolation, characterization, and primary structure of rubredoxin from the
      photosynthetic bacterium, Heliobacillus mobilis.
AB  - Rubredoxin is a small nonheme iron protein that serves as an electron carrier in
      bacterial systems. Rubredoxin has now been isolated and characterized from the
      strictly anaerobic phototroph, Heliobacillus mobilis. THe molecular mass (5671.3
      Da from the amino acid sequence) was confirmed and partial formylation of the N
      terminal methionyl residue was established by matrix-assisted laser desorption
      mass spectroscopy. The complete 52-amino-acid sequence was determined by a
      combination of N-terminal sequencing by Edman degradation and C-terminal
      sequencing by a novel method using carboxypeptidase treatment in conjunction with
      amino acid analysis and laser desorption time of flight mass spectrometry. The
      molar absorption coefficient of Hc. mobilis rubredoxin at 490 nm is 6.9 mM-1 cm-1
      and the midpoint redox potential at pH 8.0 is -46 mV. The EPR spectrum of the
      oxidized form shows resonances at g = 9.66 and 4.30 due to a high-spin ferric
      iron. The amino acid sequence is homologous to those of rubredoxins from other
      species, in particular, the gram-positive bacteria, and the phototrophic green
      sulfur bacteria, and the evolutionary implications of this are discussed.

PMID- 7726578
TI  - Primary structure of a coagulant enzyme, bilineobin, from Agkistrodon bilineatus
      venom.
AB  - The amino acid sequence and disulfide bridge location of the coagulant enzyme,
      named bilineobin, isolated from the venom of Agkistrodon bilineatus was
      determined by Edman sequencing of the peptides derived from digests with cyanogen
      bromide, clostripain, Staphylococcus aureus V8 protease, trypsin, and
      chymotrypsin. This enzyme has a molecular weight of 57,000 Da by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis; however, bilineobin consists of 235
      amino acids and has a calculated molecular weight of 26,481. The enzyme contains
      fucose, GlcNAc, galactose, mannose and NeuAc and six N-linked glycosylation
      consensus sites. The carboxyterminal amino acid, proline, was determined using
      carboxypeptidase Y. The six disulfide bonds of bilineobin link Cys78 to Cys234,
      Cys120 to Cys188, Cys178 to Cys203, Cys7 to Cys141, Cys152 to Cys167, and Cys28
      to Cys44. The amino acid sequence similarity to flavoxobin (T.C. Shieh et al.,
      1988, J. Biochem (Tokyo) 103, 596-605) and batroxobin (N. Itoh et al., 1987, J.
      Biol. Chem. 262, 3132-3135) was 67%. The deglycosylated enzyme more rapidly
      generated fibrinopeptide A than native bilineobin.

PMID- 7726580
TI  - Treatment of chromomycosis with oral high-dose amphotericin B.

PMID- 7726579
TI  - Drug action of ritodrine on the sarcoplasmic reticulum Ca(2+)-ATPase from
      skeletal muscle.
AB  - Ritodrine inhibits the steady-state Ca(2+)-ATPase activity of isolated
      sarcoplasmic reticulum vesicles in a dose-dependent manner. The observed K0.5
      value for inhibition (approximately 3 mM) gives proof of a low-affinity
      interaction. Ritodrine also interferes with the steady-state Ca2+ transport
      ability decreasing the maximal rate without modification of the Ca2+ or ATP
      affinity for the enzyme. This is consistent with an absence of competition for
      the transport and the catalytic sites. Analysis of the catalytic and transport
      cycle shows that: (i) ritodrine inhibits the phosphorylation partial reaction.
      This is supported by pre-steady-state kinetic experiments of Ca2+ transport and
      also by the temperature dependence of the phosphoenzyme level. (ii) At high
      ritodrine concentrations the dephosphorylation step becomes rate-limiting. This
      is suggested by the biphasic profile (V-shape) of phosphoenzyme accumulation at
      different ritodrine concentrations. This was also confirmed by chase experiments
      of radioactive phosphoenzyme decomposition at steady state. These data reveal a
      complex pattern of inhibition involving two sites for interaction with low and
      high ritodrine concentrations. It is envisaged that ritodrine does not exert any
      direct effect on the smooth muscle sarcoplasmic reticulum Ca(2+)-ATPase when used
      in the treatment of preterm birth.

PMID- 7726581
TI  - A personal perspective on residency education.
AB  - Much blame for what ails residency education has been heaped on limited
      resources, the rapid growth in medical knowledge and technology, shifts in
      lifestyle attitudes of trainees, and marked changes affecting the health care
      industry. By contrast, less heed has been given to the possibility that inertia
      and ineffective leadership or oversight may be the major stumbling blocks to
      better education. This essay is dedicated to the belief that what residents are
      taught and how they are taught are of seminal importance to the future of our
      specialty. It focuses attention on constructive mechanisms and strategies that,
      if employed, might improve the processes of teaching and learning during
      residency. Finally, it advances the notion that all dermatologists (academicians
      and community practitioners alike) should harbor concern and demonstrate
      responsibility for the education of our future colleagues.

PMID- 7726582
TI  - The effect of regular sunscreen use on vitamin D levels in an Australian
      population. Results of a randomized controlled trial.
AB  - BACKGROUND AND DESIGN: Studies published have suggested a possibility that
      regular use of sunscreen to prevent skin cancer may put the population,
      particularly elderly people, at risk of vitamin D deficiency. We aimed to
      determine whether regular use of sunscreens in the normal adult population, as
      recommended by public health authorities for the prevention of skin cancer, may
      put individuals at risk of vitamin D deficiency. A randomized double-blind
      control trial of the daily use of a broad-spectrum sunscreen (sun protection
      factor [SPF] 17) vs placebo cream over a summer period in Australia was conducted
      in 113 people aged 40 years and over, with sampling stratified by age. All
      participants had at least one solar keratosis. Serum samples taken at the
      beginning and at the end of the study were analyzed for 25-hydroxyvitamin D3 and
      1,25-dihydroxyvitamin D3. RESULTS: Mean levels of 25-hydroxyvitamin D3 rose
      significantly by the same amount in both groups over the period of the study
      (placebo, +12.8 mmol/L; sunscreen, +11.8 mmol/L). Mean levels of 1,25
      dihydroxyvitamin D3 increased significantly in the placebo group only (placebo,
      +10.8 pmol/L; sunscreen, +1.3 pmol/L), but for no subject in either group was the
      level of 1,25-dihydroxyvitamin D3 outside the reference range either at the start
      or at the end of the study. There were no significant differences by age, sex,
      and skin type in the change in 25-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3
      over the study period. CONCLUSIONS: No person, including those aged 70 years and
      over, developed any vitamin D levels outside the normal reference range during
      the period of the study. The data suggest that over an Australian summer
      sufficient sunlight is received, probably through both the sunscreen itself and
      the lack of total skin cover at all times, to allow adequate vitamin D production
      in people who are recommended to use sunscreens regularly. More work is required
      to elucidate the relationship between 25-hydroxyvitamin D3 and 1,25
      dihydroxyvitamin D3, particularly during the different seasons of the year.

PMID- 7726583
TI  - Skin cancer screening focusing on melanoma yields more selective attendance.
AB  - BACKGROUND: Screening theoretically reduces death and morbidity from malignant
      melanoma. The rationale of screening for nonmelanoma skin cancer is more
      debatable, since mortality is very low. METHODS: We organized a screening
      campaign in Southern Limburg, the Netherlands, in 1993. Press releases and public
      announcements referred only to melanoma. The results were compared with similar
      campaigns in Arnhem and Eindhoven, the Netherlands, in 1990; these, however,
      addressed skin cancer in general. RESULTS: There were 4146 people attending the
      1993 screenings, compared with 2463 in 1990. The proportion of screenees with
      lesions suggestive of melanoma increased from 1.1% in 1990 to 1.7% during the
      1993 campaign (P = .04). The proportion of dysplastic nevi rose from 2.1% to 7.7%
      (P < .001). Nonmelanoma skin cancers were less often encountered (3.7% in 1990 vs
      2.6% in 1993; P = .009). Actinic keratoses were also less numerous (6.3% vs 1.5%;
      P < .001). CONCLUSION: Screening concentrating on melanoma increases the rates of
      lesions suggestive of melanoma and dysplastic nevi, whereas the proportions of
      basal and squamous cell carcinomas and actinic keratoses decrease. These findings
      may have important implications with regard to the cost-effectiveness of skin
      cancer screening efforts.

PMID- 7726584
TI  - Socioeconomic status and attitudes of 51 patients with giant basal and squamous
      cell carcinoma and paired controls.
AB  - BACKGROUND: Giant nonmelanoma skin cancers are disfiguring and clearly visible.
      This prospective study examined tumor characteristics, ie, location, tumor type,
      duration, and the socioeconomic status and attitudinal characteristics of these
      patients and their interactions with the medical community. DESIGN: From 1979
      through 1993, preoperative questionnaires about age, sex, tumor duration, prior
      treatment, socioeconomic status, and attitudinal concerns were completed by 51
      patients with giant tumors and randomly matched controls. Additional data
      completed by the physician included tumor type, location, and preoperative
      clinically apparent diameter of the tumor. RESULTS: Giant tumors were more
      frequent on the scalp in men. Lower socioeconomic status and infrequent physician
      visits were characteristic of those with giant lesions. Those with giant lesions
      were less concerned about their general health, had a greater sense of shame
      about their appearance, had greater belief that since prior treatment did not
      help the problem then nothing else would, and had an increased frequency of
      perceived prior reassurance. Women and those younger than 65 years of both sexes
      were more concerned about economic costs and/or the time lost from work or caring
      for others. CONCLUSIONS: Health promotion by early detection and treatment of
      these nonmelanoma skin cancers in elderly men could prevent extensive surgical
      efforts later in the course of the disease. Skin screening examinations by all
      physicians and better public awareness of the signs of skin cancer, especially
      among elderly men, would enhance early detection; however, it is not clear that
      early detection by physicians enables treatment. Strategies to assist individuals
      in overcoming their barriers to accessing care need to be provided.

PMID- 7726585
TI  - Malignant melanoma and other second cutaneous malignancies in cutaneous T-cell
      lymphoma. The influence of additional therapy after total skin electron beam
      radiation.
AB  - BACKGROUND: Previous large studies have shown that patients with cutaneous T-cell
      lymphoma are at increased risk for basal cell carcinoma and squamous cell
      carcinoma, and anecdotal case reports have suggested an association with
      malignant melanoma. It has been postulated that the exposure of cutaneous
      structures to potentially carcinogenic therapies, such as ionizing radiation or
      alkylating agents, might be causally associated with the development of these
      second cutaneous malignancies, but, to date, no study has directly addressed this
      issue. The purpose of this study was to evaluate the occurrence of second
      cutaneous malignancies in a group of patients with cutaneous T-cell lymphoma
      treated with total skin electron beam therapy and to examine the additional
      effects of oral psoralen with UV-A phototherapy, topical mechlorethamine
      hydrochloride therapy, and further radiation therapy. One hundred sixty-four
      patients with cutaneous T-cell lymphoma who had received total skin electron beam
      therapy between 1974 and 1990 were identified, and information was abstracted
      from their records. RESULTS: Six patients developed malignant melanoma 12 to 95
      months after total skin electron beam therapy. Of the six patients, three had
      received oral psoralen with UV-A as additional therapy and two had received
      topical mechlorethamine. None had received additional radiation therapy. Twenty
      four patients developed more than 37 basal cell carcinomas and 34 squamous cell
      carcinomas from 11 months to more than 10 years after total skin electron beam
      therapy. Of the 24 patients, 15 had received oral psoralen with UV-A and 12 had
      received mechlorethamine as additional therapy. Additional radiation therapy had
      been administered to nine patients. During a median follow-up of 6 years, no
      patients died of any second cutaneous malignancy. CONCLUSION: We found a high
      rate of both melanoma and nonmelanoma skin cancer. The additional use of
      mechlorethamine or oral psoralen plus UV-A, but not radiation, was significantly
      associated with the development of basal cell carcinoma and squamous cell
      carcinoma, but not malignant melanoma.

PMID- 7726586
TI  - The morphologic criteria of the pseudopod in surface microscopy.
AB  - BACKGROUND AND DESIGN: In vivo cutaneous surface microscopy (oil epiluminescence,
      dermatoscopy, and dermoscopy) has been shown to greatly enhance the clinical
      diagnosis of melanoma. The pseudopod is a morphologic feature seen on surface
      microscopy that corresponds to the radial growth of tumor in melanoma. While it
      is one of the most specific surface microscopic features of invasive melanoma, it
      has remained poorly defined. We studied 239 pigmented lesions, 80 melanomas (62
      invasive and 18 in situ) and 159 randomly selected pigmented nonmelanomas. We
      photographed these lesions in vivo using immersion oil and a Heine Dermaphot
      camera (Heine Ltd, Herrsching, Germany). We then scored the lesions in a
      "blinded" fashion for the presence of pseudopods based on strictly defined
      morphologic criteria. RESULTS: We defined the morphologic criteria of the
      pseudopod. As defined, the pseudopod retained a 97% specificity and 23%
      sensitivity for invasive melanoma. No difference was seen in the mean Breslow
      thickness between melanomas with and without pseudopods. None of the in situ
      melanomas were observed to have pseudopods. CONCLUSION: We suggest morphologic
      criteria for a highly specific in vivo cutaneous surface microscopic feature of
      invasive melanoma, the pseudopod.

PMID- 7726587
TI  - Polymerase chain reaction detection of circulating melanocytes as a prognostic
      marker in patients with melanoma.
AB  - BACKGROUND AND DESIGN: Polymerase chain reaction (PCR) detection of circulating
      tumor cells from malignant melanoma (MM) was recently described, but the
      prognostic value of this method in the treatment of patients with MM remained
      unclear. In the present prospective study, blood samples (n = 193) were collected
      from 93 patients with MM: 10 stage I patients after primary tumor resection, 18
      patients with regional lymph node metastases before node resection, 33 disease
      free but high-risk patients (previously treated for node metastases), and 32
      patients with distant metastases. Circulating melanocytes were detected using a
      reverse transcriptase PCR method that analyzes tyrosinase gene expression. All
      patients were kept under regular surveillance. RESULTS: The PCR assay was always
      negative in normal individuals and in subjects with non-MM metastatic cancer,
      while it was positive in 16 of 32 patients with disseminated MM. Five of eight
      patients who were PCR-positive before node dissection vs one of 10 who were PCR
      negative relapsed within 6 months after surgery. In high-risk but apparently
      disease-free patients, the risk of relapse within the next 6 months was 3.8 times
      higher after a positive test result. In patients with distant metastases, a
      positive PCR predicted rapid disease progression. CONCLUSIONS: These data suggest
      that PCR detection of circulating melanocytes can be considered as a marker for
      rapid postoperative relapse after node dissection in patients with MM with
      regional node metastases, for short-term relapse in high-risk disease-free
      patients, and for rapid and severe progression in patients with distant
      metastases. This test may have a crucial interest in the treatment of patients
      with MM.

PMID- 7726588
TI  - Familial pityriasis rubra pilaris.
AB  - BACKGROUND: Familial pityriasis rubra pilaris is a rare autosomal dominant skin
      disorder. Four individuals from one family are described who demonstrate clinical
      features compatible with a diagnosis of familial pityriasis rubra pilaris.
      Results of light and electron microscopic, immunocytochemical, and biochemical
      analysis of skin biopsy specimens from three of these four individuals are
      presented. OBSERVATIONS: All affected individuals demonstrated erythematous scaly
      skin with follicular prominence and islands of sparing. Inheritance was
      consistent with an autosomal dominant trait. Light and electron microscopic
      findings were compatible with those reported in sporadic cases of pityriasis
      rubra pilaris. Immunocytochemistry showed suprabasal staining with monoclonal
      antibody AE1. Immunoblot analysis revealed abnormal keratins with K6/16
      expression, the possibility of an abnormal K14 or K16, and a 45-kd acidic keratin
      not normally expressed in epidermis. Because similar biochemical analyses have
      not been reported previously in other cases of pityriasis rubra pilaris (familial
      or sporadic), comparisons cannot be made. CONCLUSIONS: The observations suggest
      that the cutaneous abnormality in this family extends beyond clinical and
      morphological alterations to abnormalities in biochemical markers of epidermal
      differentiation.

PMID- 7726589
TI  - Congenital generalized follicular hamartoma associated with alopecia and cystic
      fibrosis in three siblings.
AB  - BACKGROUND: Generalized follicular hamartoma is a rare condition that has been
      described in association with alopecia, myasthenia gravis, and circulating
      autoantibodies. To date, all reported cases have appeared in female individuals.
      We report a kindred in which three siblings were affected by this condition in
      association with alopecia and cystic fibrosis. OBSERVATIONS: Three children of
      two consanguineous patients were affected by cystic fibrosis. They also had the
      same phenotype characterized by senilized facies, partial alopecia, and
      hypohidrosis, severe retardation of physical growth, and hyperelasticity of the
      skin. In all three children, skin biopsy specimens revealed the presence of
      basaloid proliferations at the level of the hair follicles that could not be
      demonstrated in their healthy parents. Myasthenia gravis did not appear during
      the clinical course of our patients, and circulating autoantibodies were not
      detected. All three patients died during childhood due to complications of cystic
      fibrosis. CONCLUSIONS: Generalized follicular hamartoma is a rare condition
      previously reported in association with alopecia, myasthenia gravis, and/or
      circulating autoantibodies (antinuclear and antiacetylcholine receptor
      antibodies). These are the first congenital cases of generalized follicular
      hamartoma described, and it is also the first time that an association with
      cystic fibrosis is reported. The striking association of generalized follicular
      hamartoma with cystic fibrosis in these three siblings suggests that there may be
      a genetic linkage between the two conditions.

PMID- 7726590
TI  - Self-healing juvenile cutaneous mucinosis.
AB  - BACKGROUND: Mucinoses represent a puzzling and heterogeneous group of rare
      diseases, and self-healing juvenile cutaneous mucinosis is an extremely rare
      disease among them. OBSERVATIONS: A scleroedematous condition of the face,
      associated with papular lesions and arthropathies, had occurred in a 5-year-old
      boy 10 days after onset of fever, arthralgia, muscle tenderness, and weakness.
      RESULTS: Histologic examination revealed an edematous dermis, occupied by mucin.
      Skin lesions and the joint swellings disappeared spontaneously after 2 months. At
      the follow-up 5 years later, the patient remains in excellent health. CONCLUSION:
      Although exceptional, this entity has a well-defined clinical picture, marked by
      manifestations that are initially worrisome but which, surprisingly, prove to be
      temporary and benign.

PMID- 7726592
TI  - Adverse drug interactions clinically important for the dermatologist.
AB  - BACKGROUND: All physicians, including dermatologists, are at risk for prescribing
      drugs that interact in a harmful way. Although prescribing a harmful drug
      combination may have serious consequences, no review has examined the drug-drug
      combinations that are of greatest concern for dermatologists. Our goal is to
      review the pharmacologic mechanisms of adverse drug interactions, the risky
      drugs, and the patients who are most vulnerable. In so doing, we hope to provide
      guidance through a potential minefield of adverse interactions. OBSERVATIONS:
      Although there are only sparse epidemiologic data regarding the prevalence or
      cost of adverse drug interactions in dermatology, the consequences may range from
      a minor loss of therapeutic effect of an administered agent to a life-threatening
      toxic reaction. We will review methotrexate, cyclosporin A, antifungal agents,
      antibiotics, retinoids, and antihistamine interactions with each other and with
      other systemic medications. CONCLUSIONS: An organized reporting system needs to
      be developed so that statistically meaningful epidemiologic data can be obtained
      for adverse drug interactions, such as the Medwatch program recently proposed by
      the Food and Drug Administration. Such a system will provide valuable data
      regarding drug combinations that may be dangerous and determine the scope of the
      problem as a public health issue.

PMID- 7726591
TI  - Summer in Australia. Skin cancer and the great SPF debate.

PMID- 7726593
TI  - Skin cancer control in Australia. The balance between primary prevention and
      early detection.

PMID- 7726594
TI  - Draining ulcers with lymphadenopathy. Metastatic basal cell carcinoma.

PMID- 7726595
TI  - Small red nodule on the leg of a young woman. Microvenular hemangioma.

PMID- 7726596
TI  - Purpuric nodules along a surgical scar. Metastatic malignant mesothelioma of the
      tunica vaginalis testis.

PMID- 7726597
TI  - Multiple erythematous papules on the back of a patient with ankylosing
      spondylitis. Multiple basal cell carcinomas (BCCs) secondary to radiation
      exposure.

PMID- 7726599
TI  - Pearly penile papules on the shaft.

PMID- 7726598
TI  - Minocycline as possible cause of severe and protracted hypersensitivity drug
      reaction.

PMID- 7726601
TI  - Effects of 0.1% retinoic acid on Bateman's actinic purpura.

PMID- 7726600
TI  - Pregnancy outcome after periconceptional and first-trimester exposure to
      methoxsalen photochemotherapy.

PMID- 7726603
TI  - Generalized linear porokeratosis treated with etretinate.

PMID- 7726602
TI  - Topical cyclosporine in the treatment of oral and vulvar erosive lichen planus: a
      blood level monitoring study.

PMID- 7726604
TI  - Gene therapy for cancers.

PMID- 7726605
TI  - Hypertrophic cardiomyopathy.

PMID- 7726606
TI  - Cognitive abilities associated with the Silver-Russell syndrome.
AB  - There is no consensus opinion on whether or not cognitive impairments are found
      in the Silver-Russell syndrome. An investigation of a substantial sample was
      undertaken, using standardised assessments, in 20 boys and five girls aged 6.0
      years to 11.8 years. Mean (SD) birth weights were -2.65 (0.95) SD scores,
      corrected for gestation. At evaluation the children had a mean (SD) age of 8.8
      (1.8) years and a mean height of -2.26 (1.5) SD scores. Tests of cognitive
      abilities included assessments of general intelligence, reading and arithmetic
      attainments, and a cognitive processing task. Most had some degree of
      developmental delay: mean (SD) full scale IQ was 86 (24); 32% scored within the
      learning disability range (that is, IQ < 70); 40% were reading at least 24 months
      below their chronological age. Current head circumference correlated highly with
      full scale IQ. Assessments of special educational needs had been completed on
      36%; 48% were receiving speech therapy. Approximately half of children with the
      Silver-Russell syndrome have significant impairment of their cognitive abilities.

PMID- 7726607
TI  - Potentially dangerous sleeping environments and accidental asphyxia in infancy
      and early childhood.
AB  - Infants and young children may be exposed to a variety of dangerous situations
      when left sleeping in cots, chairs, or beds. A review of 30 cases of accidental
      asphyxia occurring in infants and young children who had been left to sleep
      unattended was undertaken from the necropsy and consultation files of the
      Adelaide Children's Hospital. Causes of death included hanging from loose
      restrainers, clothing, or a curtain cord (12 cases), positional asphyxia/wedging
      from slipping between a mattress and bed/cot sides or wall, or from moving into a
      position where the face was covered and the upper airway occluded (16 cases), and
      suffocation from plastic bed covers (two cases). Cases of co-sleeping in bed with
      an adult and of non-accidental asphyxia were not included in this review. As the
      pathological findings were on occasion identical to those that are typically
      found in sudden infant death syndrome, adequate death scene examination was vital
      in several cases to allow identification of lethal sleeping environments and to
      enable steps to be taken to minimise the risk of future deaths due to similar
      situations. For example, two cases in which infants asphyxiated in rocking
      cradles led to the investigation of the cradles and to formulation of specific
      safety recommendations regarding the angle of tilt. Two infants who died after
      becoming wedged between the back of a couch and a co-sleeping parent in one case
      and cushions in the other, would indicate that this also represents a potentially
      lethal sleeping position. Other dangerous situations involved infant car seat
      restraints, seats with loose harnesses, cots with movable sides or projecting
      pieces, thin plastic mattress/pillow coverings, and beds with spaces between the
      mattress and cot side or wall. Lack of supervision at the time of death was a
      feature of each case.

PMID- 7726608
TI  - Surfactant abnormalities in ALTE and SIDS.
AB  - Abnormalities in the relative concentrations of the components of surfactant have
      been implicated in prolonged expiratory apnoea (PEA) and sudden infant death
      syndrome (SIDS). Controversy has, however, surrounded these findings, as they may
      be secondary to terminal life events. In this study the physical properties of
      surfactant were measured in children with recurrent apparent life threatening
      events (ALTEs), PEA, and SIDS. Bronchial lavage samples were obtained from 21
      children with recurrent ALTEs, two SIDS victims, and 26 control patients. Lipid
      components were immediately elutriated from these samples with liquid chloroform.
      The physical properties of the extracted surfactant were studied on a Langmuir
      trough in which the area (A) of the monolayer was cycled continuously as the
      surface tension (gamma) was measured by the Wilhelmy method using a platinum
      'flag'. The investigators performing these tests were unaware of the clinical
      diagnosis. Twenty one of 23 patients displayed abnormal physical properties while
      seven of 26 controls displayed similar abnormalities. These abnormalities were
      partially inverted hysteresis (figure of eight) loops and inverted
      (anticlockwise) loops that also generally exhibited less hysteresis. Of the 26
      controls 20 exhibited a wide hysteresis pattern that cycled in a normal
      (clockwise) direction. These differences were significantly different. It is
      concluded that children with recurrent ALTEs have definable abnormalities in the
      physical properties of surfactant and that these findings may provide a sensitive
      means of identifying those at risk of recurrent ALTEs and SIDS.

PMID- 7726609
TI  - Blood eosinophils, leukotriene C4 generation, and bronchial hyperreactivity in
      formerly preterm infants.
AB  - Infants born prematurely are known to display longstanding bronchial
      hyperreactivity. The mechanism responsible for this is still unclear. Eosinophils
      are thought to play a central part in the development of bronchial
      hyperreactivity in asthma. It was the aim of this study to assess the relation of
      bronchial hyperresponsiveness to potential markers of eosinophilic inflammation
      in peripheral blood. Eosinophil count, the concentration of serum eosinophilic
      cationic protein, the capacity of purified eosinophils to generate leukotriene
      C4, and bronchial reactivity was studied in 24 non-atopic children born
      prematurely, 12 healthy controls, and 12 children with asthma aged 6 to 9 years.
      There was no difference in serum concentrations on eosinophil cationic protein
      and eosinophil counts. However, eosinophils from the 15 formerly preterm infants
      with significant bronchial hyperreactivity generated significantly higher amounts
      of leukotriene C4 than normal controls and prematurely born children without
      bronchial hyperreactivity. Levels of leukotriene C4 in this group were comparable
      with those obtained with eosinophils from patients with asthma. In contrast with
      cells from the other groups, eosinophils from the children with bronchial
      hyperreactivity born prematurely show no enhancement of leukotriene C4 generation
      on prestimulation with platelet activating factor. It is concluded that bronchial
      hyperreactivity of children born prematurely is accompanied by the prestimulation
      of eosinophils.

PMID- 7726610
TI  - Pupil size in diabetes.
AB  - Sympathetic function was studied in 101 diabetic children and 102 age and sex
      matched control children, as part of a longitudinal study of the evolution of
      microvascular disease in the population of diabetic children and adolescents in
      Avon County. The median (range) age of the diabetic population was 13.5 (6.0
      17.2) years, the duration of diabetes was 4.0 (0.4-13.9) years, and glycated
      haemoglobin (HbA1) was 10.9 (7.0-18.1)%. Pupillary adaptation in darkness, as an
      index of sympathetic neuropathy, was measured using a Polaroid portable
      pupillometer. Diabetic children had a significantly smaller median pupillary
      diameter, measured as the pupil/iris ratio and expressed as a percentage, than
      control children (median (range) 62.9 (50.3-72.1) v 65.9 (52.2-73.8)). Pupillary
      diameter was significantly related to diabetes duration (r = -0.22), HbA1 (r = 
      0.34), systolic blood pressure (r = -0.25), diastolic blood pressure (r = -0.49),
      and mean albumin/creatinine ratio on random urine samples (r = -0.26). Pupillary
      diameter was not related to age (r = -0.1). Eight (7.9%) diabetic and four (3.9%)
      control children were identified as having abnormal pupillary dilation in
      darkness. In comparison with the rest of the diabetic population, these diabetic
      children had longer diabetes duration and poorer glycaemic control. Polaroid
      pupillometry has demonstrated subclinical autonomic neuropathy in a population of
      diabetic children and adolescents. These abnormalities were related to poor
      metabolic control, long diabetes duration, and also to other indices of
      microvascular disease.

PMID- 7726611
TI  - Birth weight and head circumference standards for English twins.
AB  - This study was undertaken to provide reliable up to date information on birth
      weights and occipitofrontal head circumference measurements in relation to
      gestational age for English newborn twins. Records from 36 maternity units in
      England, mainly from 1988-92, have provided data on birth weights for over 19,000
      newborn twins with gestational ages ranging from 23 to 41 weeks, and on head
      circumference measurements for over 5300 twins ranging from 28 weeks to 40 weeks'
      gestation. Centile charts have been produced for boy and girl twins showing the
      distribution of these values against gestational age. The findings confirm the
      greater weights of boys compared with girls throughout, increasing from a mean of
      about 50 g at early stages to 100 g later, in a similar way to that reported for
      singletons. Twins were lighter than comparable singletons by about 100 g at 24
      weeks, increasing progressively to 4-500 g at 38 weeks' gestation. In contrast,
      differences in occipitofrontal head circumferences between singletons and twins
      were only evident with gestations longer than 35 weeks--and from 37 weeks'
      gestation onwards the mean head circumference of singletons exceeded that of
      twins by about 5 mm. It is recommended that in evaluating the significance of the
      birth weight of a twin in relation to gestation, twin standards such as the ones
      presented here should be used rather than those relating to singletons.

PMID- 7726612
TI  - Alternative treatment to corticosteroids in steroid sensitive idiopathic
      nephrotic syndrome.
AB  - A review was undertaken of the use of alternative immunosuppressive treatment in
      addition to corticosteroids in a cohort of 429 children with steroid sensitive
      nephrotic syndrome (SSNS) treated between 1980 and 1994. Two hundred and twenty
      two children (52%) received at least one course of alternative treatment, 98
      (23%) two, and 43 (10%) three. Cyclophosphamide was administered to 196 children
      (46%); in 181 it was the first course of alternative treatment and in 104 (57%)
      of those it was also the last ('final course'). Levamisole was given to 56
      children (13%) and cyclosporin to 53 (12%). Fifteen children in whom cyclosporin
      failed were treated with chlorambucil. A few patients received azathioprine or
      vincristine. Ten children developed secondary steroid resistance, of whom five
      progressed to chronic renal failure. Acute complications included reversible
      renal failure, septicaemia, peritonitis, convulsions, and cerebral thrombosis.
      There were three deaths. It is concluded that half of the referred children with
      SSNS were deemed to require at least one course of alternative immunosuppressive
      treatment, and that side effects of the treatment and complications of SSNS are
      infrequent but occasionally fatal.

PMID- 7726613
TI  - Manganese in long term paediatric parenteral nutrition.
AB  - The current practice of providing manganese supplementation to neonates on long
      term parenteral nutrition is leading to a high incidence of hypermanganesaemia.
      Magnetic resonance imaging (MRI) studies in adults on long term manganese
      parenteral nutrition have shown changes in TI weighted MRI images and similar
      findings in a neonate receiving trace element supplementation are reported here.
      Whole blood manganese concentration in the infant was 1740 nmol/l (or 8.3 times
      upper reference limit). In all neonates on long term parenteral nutrition with
      evidence of cholestatic liver disease so far investigated, the whole blood
      manganese concentrations were > 360 nmol/l (reference range 73-210). Manganese
      supplementation to patients on long term parenteral nutrition requires
      reappraisal, particularly in those who develop cholestatic liver disease
      associated with parenteral nutrition.

PMID- 7726614
TI  - A survey of recommendations given to patients going home after bone marrow
      transplant.
AB  - A postal questionnaire was sent to 11 UK Children's Cancer Study Group bone
      marrow transplant centres asking them for details of their instructions to
      patients on discharge after either allogeneic or auto transplant; nine centres
      responded. There was no recommendation on which they all agreed. Though all
      centres gave prophylactic septrin, the times of starting and stopping treatment
      varied considerably. Three centres recommended lifelong penicillin after total
      body irradiation, one treated for two years and five gave no such prophylaxis.
      Four of nine centres gave routine acyclovir for herpes simplex prophylaxis. Most
      centres suggested prophylaxis against varicella after contact exposure for one
      year. However, three gave zoster immune globulin alone, one gave this together
      with acyclovir, and five gave acyclovir alone. No two centres recommended the
      same dose of acyclovir. Vaccinations were allowed from 6-18 months after
      transplant. One centre required documentation of recovery of immune function
      first. Four centres recommended a child stay off school for six months; others
      had 'common sense' approaches. Only one centre did not allow family holidays for
      the first six months but many imposed restrictions on these holidays. Dietary
      restrictions varied greatly between centres. It is concluded that there is a need
      for unified and scientifically justified guidelines after transplant for
      paediatric bone marrow transplant patients.

PMID- 7726615
TI  - Preventative policies in transfusion associated graft versus host disease in the
      treatment of cancer.
AB  - Experience of transfusion associated graft versus host disease (TA-GvHD) and
      current preventative policy in 22 UK children's cancer centres was established by
      questionnaire. Cellular blood products were irradiated in all centres during bone
      marrow transplantation, but there was no consensus for children receiving
      standard chemotherapy. Irradiation dose varied from 1500-5000 cGy and was below
      2500 cGy in 12 units. Five cases of TA-GvHD were identified; all five children
      died.

PMID- 7726616
TI  - Systemic vasculitis complicating infantile autoimmune enteropathy.
AB  - An infant with unexplained sideroblastic anaemia and severe protracted diarrhoea
      due to autoimmune gut disease is reported. Despite treatment with an exclusion
      diet and immunosuppressive agents she developed a severe systemic vasculitic
      illness. Intensive treatment with plasmapheresis resulted in resolution of the
      vasculitic process but the child subsequently died after overwhelming
      septicaemia.

PMID- 7726617
TI  - Cycle helmet wearing in teenagers--do health beliefs influence behaviour?

PMID- 7726618
TI  - Child casualties in a Croatian community during the 1991-2 war.

PMID- 7726619
TI  - The use of haemopoietic growth factors in blood disorders.

PMID- 7726620
TI  - Child health statistical review.

PMID- 7726621
TI  - Intravenous midazolam in small bowel biopsy.

PMID- 7726622
TI  - Jet nebulising systems for recombinant human DNase I.

PMID- 7726623
TI  - Adverse events occurring during interhospital transfer of the critically ill.

PMID- 7726624
TI  - Patterns of scald injuries.

PMID- 7726625
TI  - Attitudes and beliefs of Muslim mothers towards pregnancy and infancy.

PMID- 7726626
TI  - The first chairs and professors of dermatology, particularly of 'German'
      dermatology.
AB  - A short outline is given of the establishment of the first chairs in
      dermatology/venerology in Central Europe, starting with the award of the
      Fothergillian Gold Medal to Robert Willan in 1790 and ending past mid-century
      with the establishment of the professorial chairs in Munich in 1863 and of
      Military Dermatology at the Vienna Surgical Academy in 1870.

PMID- 7726627
TI  - Proinflammatory properties of molluscum bodies.
AB  - Molluscum contagiosum, a condition characterized by benign viral tumours,
      occasionally becomes inflamed and regresses spontaneously, an event probably
      initiated by a host cell-mediated immune rejection against the lesion, but it
      inevitably involves the disruption of the epidermal tissue to expose the
      molluscum bodies to the tissue fluids of the dermis. It has been suggested that
      the molluscum bodies induce inflammation by a mechanism similar to that involved
      in ruptured epidermal cysts or in acne. Despite the occasional development of
      inflammation in molluscum contagiosum, the proinflammatory properties of
      molluscum bodies have never been studied in vitro. Thus, in the present study we
      sought to determine whether molluscum bodies exert a proinflammatory effect by
      inducing neutrophil chemotaxis. When exposed to fresh serum in vitro, water
      insoluble components of molluscum bodies activated the alternative complement
      pathway to produce chemotactic C5a/C5a des Arg. We also found that an aqueous
      extract of molluscum bodies exerted potent chemotactic activity for neutrophils.
      Remarkably high amounts of the immunoreactive proinflammatory cytokines IL-8 and
      GRO alpha were present in the extract even when compared with psoriatic scale
      extracts. Gel filtration HPLC of the extract demonstrated the presence of
      neutrophil chemotactic activity over a wide range of molecular mass. These data
      suggest that disruption of the epidermal wall of molluscum bodies induces acute
      inflammatory changes by activation of the alternative complement pathway on
      exposure to the tissue fluids, and that the molluscum bodies themselves release
      proinflammatory cytokines and other neutrophil chemotactic factors on
      decomposition.

PMID- 7726628
TI  - Role of the extracellular matrix in the degradation of connective tissue.
AB  - Cell-matrix interactions have an important impact on regulating connective tissue
      degradation during physiological and pathological processes, e.g., development,
      wound healing and tissue remodeling and tumor invasion and metastasis. Connective
      tissue breakdown is initiated by a specific class of enzymes, the matrix
      metalloproteinases, which include the type I collagenases, the type IV
      collagenases/gelatinases and the stromelysins and which vary with respect to
      their substrate specificities. The activity of the metalloproteinases is
      regulated by de novo synthesis of the proenzymes, the activation of the zymogens
      and by the presence of the inhibitors, TIMPs. This tight control is required in
      order to guarantee normal functioning of connective tissue.

PMID- 7726629
TI  - Role of cytokines in controlling connective tissue gene expression.
AB  - Recently, the role of cytokines in controlling gene expression of connective
      tissue components has been increasingly emphasized. Many cytokines have been
      shown to have specific effects on gene expression of connective tissue
      components, and the roles of cytokines in controlling connective tissue
      metabolism during wound healing and in fibrosis have increasingly been discussed.
      In this article, the effects of cytokines on regulation of gene expression of
      connective tissue components, especially of type I collagen were described. We
      analysed transcriptional control of the alpha 1(I) collagen gene by TNF-alpha by
      means of DNA mediated transfection experiments using recombinant plasmids in
      which the promoter region of the human alpha 1(I) collagen had been fused to the
      chloramphenicol acetyl-transferase (CAT) gene, in human dermal fibroblasts. It
      was found that TNF-alpha reduced alpha 1(I) collagen transcription through at
      least up to -107 bp upstream of the human alpha 1(I) collagen promoter gene in
      dermal fibroblasts.

PMID- 7726630
TI  - Strategies to reduce mortality from cutaneous malignant melanoma.
AB  - The incidence of cutaneous malignant melanoma continues to rise. Strategies to
      reduce mortality in this situation include improving therapy, encouraging earlier
      diagnosis, and promoting prevention. New developments such as epiluminescence,
      sentinel node biopsy, arterial limb perfusion and the use of vaccines are
      discussed in this context.

PMID- 7726632
TI  - The skin immune system: lupus erythematosus as a paradigm.
AB  - Lupus erythematosus (LE) was first described as a clinical dermatological entity
      in 1851. The possibility of serious systemic manifestations became recognized by
      1872 as the result of the work of M. Kaposi. Since then, it took a long time
      before LE was recognized to be an immunological disease. Recognition of
      antinuclear antibodies and their deposition at the basal membrane region in skin
      resulted in two concepts of LE pathogenesis. In one, antibody complexing and
      complement activation with generation of the membrane attack complex (C5-C9) is
      thought to be the origin of the chronic inflammatory reaction. In the other,
      antibody deposition enables antibody dependent cellular cytotoxicity, leading to
      hydropic degeneration of the basal epidermal layer and subsequent chronic
      inflammation. Norris postulated in 1993, that the epidermis acts as a pro
      inflammatory organ, in which an UVB-induced increase in cytokine production is
      followed by increased expression of adhesion molecules on keratinocytes as well
      as dermal endothelial cells. Translocation of certain antigens (i.e. Ro & La) to
      which circulating auto-antibodies exist in LE, enables recognition by adhesion
      molecule directed skin-invading T cells with subsequent cytotoxic effector
      activity. A persistent chronic inflammatory reaction then ensues. A similar
      development in knowledge may be seen in the history of immunodermatology.
      Originally, lupus erythematosus could not be recognized as an immune disease,
      since concepts of immunology were virtually non-existent when LE was first
      described. Immunology, In the first half of this century, was mainly antibody
      oriented and thus came the concept of (S)LE as an antibody-mediated
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726631
TI  - Molecular basis for the dystrophic forms of epidermolysis bullosa: mutations in
      the type VII collagen gene.
AB  - Significant progress has recently been made in understanding the molecular basis
      of heritable skin diseases, such as epidermolysis bullosa, a group of mechano
      bullous genodermatoses. In particular, the dystrophic forms of epidermolysis
      bullosa have been shown to result from distinct mutations in the gene encoding
      type VII collagen, the major, if not the exclusive, component of the anchoring
      fibrils. These mutations result in deficient synthesis and/or altered assembly of
      the anchoring fibrils, thus compromising the integrity of the cutaneous basement
      membrane zone. The mutations in the type VII collagen gene have implications for
      understanding the structure-function relationships of the type VII collagen
      molecule, and also provide the basis for prenatal DNA-based diagnosis in families
      at risk for recurrence of the disease. Finally, understanding the genetic basis
      of dystrophic forms of EB sets the stage for gene therapy approaches for the
      treatment of these devastating skin diseases.

PMID- 7726633
TI  - Immunohistological analysis of anti-melanoma host responses.
AB  - Various clinical and experimental observations point to the existence of an
      immunological host defense in cutaneous malignant melanoma. To identify the major
      effector mechanisms mediating the specific anti-tumor immune response, we
      examined 23 benign and neoplastic melanocytic lesions (3 nevi, 14 primary
      melanomas, and 3 cutaneous and 3 systemic metastases) by quantitative
      immunohistology, and correlated these results with the histopathological and
      clinical subtypes of malignant melanoma. Our analyses indicate that CD3+ T-cell
      receptor alpha/beta-expressing lymphocytes are the prevailing leukocyte subset in
      primary as well as secondary malignant melanoma. We further observed that in
      early lesions (< 0.75 mm) of superficial spreading melanoma the vast majority of
      tumor-infiltrating lymphocytes (TIL) belong to the CD4+ subset and frequently
      express CD45RA antigens. In more advanced tumors, the contribution of CD8+ TIL
      gradually increases, indicating that the quality of the anti-tumor immune
      response changes during the course of the disease. Finally, we found that a
      varying percentage of cutaneous TIL express the cutaneous leukocyte antigen which
      is defined by the monoclonal antibody HECA 452 and preferentially expressed by
      skin-seeking memory T cells. In contrast, extracutaneous melanoma metastases
      (liver, brain, ovary) were completely devoid of HECA 452-reactive lymphocytes.
      These findings suggest that lymphocytes infiltrating cutaneous melanomas belong
      to a memory/effector T-cell subset functionally associated with the skin.

PMID- 7726634
TI  - Detection of HIV-specific DNA sequences in epidermal Langerhans cells infected in
      vitro by means of a cell-free system.
AB  - As dendritic antigen-presenting cells in skin and mucous membranes, Langerhans
      cells (LC) are found in areas at risk of inoculation by the human
      immunodeficiency virus (HIV). LC have been reported as targets for HIV-1. The aim
      of the present study was to investigate whether LC can be experimentally infected
      by HIV provided by a cell-free infection system. A cell-free suspensions was
      prepared from viral particles provided by chronically infected cell lines (U937
      or H9 cells) by low-speed centrifugation followed by 0.45-microns filtration. LC
      enriched epidermal cell (EC) suspensions with no CD3+ cells (assessed by flow
      cytometry and electron microscopy) and uninfected U937 cells (cell-free infection
      system control) were infected with two isolates (HTL VIII-B and RF). The
      infectiousness of the cell-free virus fluids was controlled on U937 cells where
      proviral DNA was amplified (gag, pol, and env gene sequences by the polymerase
      chain reaction, PCR) and release of virus particles into the supernatant was
      controlled either by measure of the reverse transcriptase (RT) activity or
      detection of viral RNA amplified by RT-PCR for the gag gene sequences). Proviral
      DNA (gag gene sequences) was found in LC-enriched epidermal cellular DNA from day
      4 post-infection with isolate HTL VIII-B and from day 7 with isolate RF. Although
      the RT activity did not reach a significantly high level, viral RNA was found in
      the supernatant of LC-enriched EC cultures at the same time as proviral DNA was
      detected in LC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726635
TI  - In vitro genetically aberrant T-cell clones with continuous growth are associated
      with atopic dermatitis.
AB  - Atopic dermatitis is a disease with a genetic predisposition affecting the immune
      system, with T lymphocytes participating in the immune dysregulation. Most in
      vitro T lymphocyte studies of atopic dermatitis have focused on antigen-specific
      T-cell clones. However, antigen-non-specific regulatory T lymphocytes may also
      take part in the pathway leading to antigen-specific clonal T-lymphocyte
      proliferation. T lymphocytes from skin biopsy specimens from three patients with
      severe atopic dermatitis were cultured in the presence of IL-2 and IL-4, but
      without antigen added. Initially, proliferation was oligo- or polyclonal, but in
      all cases overgrowth by T cells with clonal chromosomal aberrations was
      subsequently observed. These abnormal T-cell clones demonstrated continuous
      growth and complete or partial phenotypic loss of the T-cell antigen receptor
      complex. In summary, these findings suggest that a subset of aberrant skin-homing
      T lymphocytes is associated with atopic dermatitis.

PMID- 7726636
TI  - Treatment of severe atopic dermatitis with extracorporeal photopheresis.
AB  - Extracorporeal photopheresis using UVA irradiation of enriched lymphocytes in the
      presence of 8-methoxypsoralen (8-MOP) as a photoactivatable substrate has been
      employed for the treatment of several immunologically mediated disorders. We
      report on the first three patients subjected to extracorporeal photopheresis for
      severe atopic dermatitis. All patients had a lifelong history of atopic skin
      inflammation, and their disease had finally become resistant to well-established
      therapeutic regimes. Extracorporeal photopheresis resulted in a marked clinical
      improvement in the skin lesions of all patients. The decrease in cutaneous
      inflammatory activity became evident by the end of the second photopheresis
      cycle. In two patients skin lesions had virtually disappeared after the fifth
      treatment cycle, while in the third patient a lasting and substantial improvement
      in pruritus and erythema was achieved. Clinical remission was stable under
      maintenance therapy with prolonged intervals between photopheresis sessions.
      Therapeutic efficacy was reflected by a marked reduction in IgE serum levels in
      all three patients, while serum concentration of IgG, IgM and IgA as well as the
      profile of circulating lymphocytes remained essentially unchanged. No clinical
      signs of immunosuppression or other severe adverse events became evident.
      Collectively, our preliminary results indicate that extracorporeal photopheresis
      may interfere with the pathomechanisms leading to atopic dermatitis and therefore
      should be considered as a treatment modality for severe forms of this
      recalcitrant disorder.

PMID- 7726637
TI  - Human in vivo pharmacology of topical retinoids.
AB  - All-trans retinoic acid is used topically for treating a variety of dermatologic
      conditions ranging from acne to photoaged skin. Although the clinical effects of
      retinoic acid treatment are often considerable, relatively little is known about
      the basic mechanisms underlying such effects. With the development of an in vivo
      human assay we have investigated the pleiotypic effects of topical retinoids from
      the histologic to the molecular. Histologically, retinoic acid induces epidermal
      proliferation and differentiation coupled with dermal fibroblast production of
      collagen. Immunologic effects include stimulation of the antigen-presenting
      capacity of Langerhans cells and induction of keratinocyte ICAM-1 expression. At
      the biochemical level, retinoic acid regulates transglutaminase and tyrosinase
      activities and activates protein kinase C. Both polar metabolites and
      stereoisomers of all-trans retinoic acid are also biologically active. Molecular
      biologic techniques have revealed that elevation of mRNA for cellular retinoic
      acid binding protein II is a retinoid-related event and that nuclear receptors
      such as retinoic acid receptors and retinoid X-receptors may transduce the
      retinoid response.

PMID- 7726638
TI  - Mast cell proteinases and cytokines in skin inflammation.
AB  - The role of mast cells in provoking immediate-type hypersensitivity reactions is
      well established, but their involvement in chronic inflammation and immune
      reactions is not so clear. Mast cells synthesize and secrete large amounts of
      active proteinases, including tryptase, chymase, carboxypeptidase and cathepsin
      G, which can rapidly process numerous biologically active peptides and proteins
      or their precursors. Furthermore, mast cells are able to produce a variety of
      cytokines such as interleukin-4 (IL-4), IL-5, IL-6, tumour necrosis factor-alpha
      (TNF-alpha) and interferon-gamma (IFN-gamma) which are known to be intensively
      involved in modulating and directing inflammatory responses in the skin. In this
      review, the role of mast cell proteinases and cytokines in skin inflammation is
      discussed.

PMID- 7726639
TI  - Differential expression of heat shock protein 70 (HSP70) and heat shock cognate
      protein 70 (HSC70) in human epidermis.
AB  - Autoimmunity and microbial agents have been suggested as playing a pathogenetic
      role in psoriasis. Since immune responses to microbial infections are often
      directed towards heat shock proteins (HSP), we investigated the expression of
      three HSP families in normal and inflamed human skin. Specimens from ten patients
      with psoriasis and three patients with positive patch tests for nickel and from
      five healthy volunteers were analysed by means of immunohistochemistry. The
      patterns observed were qualitatively similar in these conditions showing only
      minor quantitative differences. Psoriatic epidermis exhibited the highest level
      of expression. HSP27, HSP70 and heat shock cognate protein 70 (HSC70) were
      readily detectable. HSP27 was homogeneously distributed throughout the epidermis,
      whereas HSP70 was restricted to the basal layer and HSC70 primarily to the
      suprabasal layers. Other HSPs were detected to a lesser degree and showed a more
      irregular pattern. Thus, the qualitative expression pattern of HSPs seems to be
      constant between different skin conditions, but the expression of constitutive
      and inducible HSP70 depends on the differentiation state of keratinocytes.

PMID- 7726640
TI  - Extraction and quantitation of cytokine mRNA from human epidermal blister roofs.
AB  - The demonstration of cytokine mRNA expression in epidermal cells by the
      polymerase chain reaction technique preceded by reverse transcription (RT-PCR)
      requires linear test conditions (i.e. that the product obtained after
      amplification reflects the relative amounts of starting material) and high
      reproducibility, specificity, and sensitivity. By combining well-defined
      techniques for mRNA extraction and concentration measurement with a sensitive and
      well-calibrated RT-PCR technique, we demonstrated the presence of IL-1 alpha, IL
      1 beta, IL-6, and TNF alpha in epidermal cells obtained from suction blister
      roofs from normal volunteers. Messenger RNA was extracted with superparamagnetic
      oligo(dT)25 Dynabeads, and the amount of mRNA was measured by spectrophotometry
      using a Beckman 5-microliters Ultra-Microcell prior to RT-PCR. Linear PCR
      conditions were obtained by carefully titrating the amounts of mRNA and the
      number of cycles. Reproducibility was estimated at different steps of the
      procedure, and the specificity of the enhanced cDNA products was verified by
      liquid hybridization with end-labelled probes. We suggest that this combination
      of techniques might prove useful for the simultaneous assessment of the
      expression of various cytokines from small samples of fresh human epidermal
      cells.

PMID- 7726641
TI  - Proopiomelanocortin production by epidermal cells: evidence for an immune
      neuroendocrine network in the epidermis.
AB  - Proopiomelanocortin (POMC) is known to be synthesized in the pituitary gland and
      is subsequently cleaved by specific prohormone convertases into biologically
      active peptide hormones such as melanocyte stimulating hormones (MSH),
      adrenocorticotropin (ACTH) and endorphins (EP). Guanine nucleotide-binding
      protein (G-protein)-coupled receptors, which have only recently been discovered,
      are involved in the transmission of their message. There is also evidence
      indicating that POMC is not only produced by pituitary cells but is an ubiquitous
      molecule, that is cleaved cell- and tissue-specific. It has also been shown that
      the epidermis keratinocytes as well as melanocytes express POMC upon stimulation
      and release alpha MSH and ACTH. In addition to their function as hormones, POMC
      peptides have been shown to exert a variety of immunoregulatory effects by
      modulating the function of immunocompetent cells as well as cytokines. These
      findings provide further evidence for the immunoneuroendocrine network playing a
      crucial role during the pathogenesis of immune and inflammatory skin disease.

PMID- 7726642
TI  - Genotraumatic T cells and cutaneous T-cell lymphoma. A causal relationship?
AB  - Mycosis fungoides, or cutaneous T-cell lymphoma (CTCL), is a T-cell mediated
      chronic inflammatory skin disease, which can occasionally progress with a
      variable time course to a fatal lymphoma or to a leukaemic form called Sezary's
      syndrome. Extensive research into CTCL has not yet elucidated the primary
      pathophysiological mechanisms. Immunohistological studies are so far less helpful
      than expected in establishing early diagnosis and prognosis of the disease. The
      proposition that an exogenous virus is the cause of CTCL has not been
      substantiated. Karyotypic analysis of lymphocytes from the skin and blood of
      patients with CTCL have shown the existence of several genetically aberrant T
      cell clones in the same patient. These changes are discussed as potential primary
      events for the development of CTCL. The hypothesis is put forward that the
      development of genotraumatic T lymphocytes is involved in the progression of the
      disease.

PMID- 7726643
TI  - Induction of rat liver drug-metabolizing enzymes by tetrachloroethylene.
AB  - The effect of tetrachloroethylene on Phase I and II drug-metabolizing enzymes in
      rat liver was examined. Rats were treated orally with tetrachloroethylene daily
      for five days, at doses of 125, 250, 500, 1,000 and 2,000 mg/kg. The higher doses
      (> 500 mg/kg) of tetrachloroethylene induced the hepatic microsomal 7
      pentoxyresorufin O-depentylase and 7-benzyloxyresorufin O-debenzylase activities
      associated with the CYP2B subfamily. 7-ethoxyresorufin O-deethylase activity was
      also induced about 2-fold compared with that of control rats at 500, 1,000, and
      2,000 mg/kg dose levels of tetrachloroethylene. However, 7-ethoxycoumarin O
      deethylase and 7-methoxyresorufin O-demethylase activities were increased
      significantly at only the 1,000 mg/kg dose level of tetrachloroethylene (1.4- and
      1.5-fold). Although other cytochrome P450-mediated monooxygenase activities such
      as nitrosodimethylamine N-demethylase, aminopyrine N-demethylase and erythromycin
      N-demethylase were also induced by tetrachloroethylene, the relative induction to
      control activity was lower than those of 7-pentoxyresorufin O-depentylase and 7
      benzyloxyresorufin O-debenzylase. Western immunoblotting showed that the levels
      of CYP2B1 and CYP2B2 proteins in liver microsomes were increased at doses of
      1,000 and 2,000 mg/kg of tetrachloroethylene. In addition to cytochrome P450
      mediated monooxygenases, there was significant induction of the Phase II drug
      metabolizing enzymes, DT-diaphorase, glutathione S-transferase activities towards
      1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene, and UDP
      glucuronyltransferase activities towards 4-nitrophenol and 7-hydroxycoumarin. The
      results indicate that tetrachloroethylene induces both Phase I (CYP2B-mediated
      monooxygenase) and Phase II drug-metabolizing enzymes (DT-diaphorase, glutathione
      S-transferase and UDP-glucuronyltransferase) in the rat liver.

PMID- 7726644
TI  - Acute and long-term effects of nine chemicals on the Japanese medaka (Oryzias
      latipes).
AB  - Ninety-six-hour acute and 28-day larval survival and growth tests were conducted
      with nine organic chemicals, using the Japanese medaka (Oryzias latipes) as the
      test organism. The nine tested chemicals were allyl isothiocyanate, aniline,
      benzyl acetate, 4-chloroaniline, 2-chloroethanol, 2,4-diaminotoluene, 1,2
      dibromoethane, 2,4-dichlorophenoxyacetic acid (2,4-D), and phenol. The derived 96
      h LC50 values for medaka for all chemicals ranged from 0.077 mg/L for allyl
      isothiocyanate to 2,780 mg/L for 2,4-D. The chronic values for six of the nine
      chemicals tested ranged from 0.013 mg/L for allyl isothiocyanate to 42.5 mg/L for
      2,4-D. Acute-to-chronic ratios for these six chemicals ranged from 1.4 for 2
      chloroethanol to 70.9 for 2,4-D. Growth of medaka was significantly reduced in
      the lowest exposure concentration during 28-dy larval tests with aniline, 4
      chloroaniline, and 2,4-diaminotoluene. The estimated maximum acceptable toxicant
      concentration was reported as less than the lowest exposure concentration of 4.6,
      2.2 and 40.3 mg/L for tests with aniline, 4-chloroaniline and 2,4-diaminotoluene,
      respectively. Chronic values for 2-chloroethanol and medaka were 12.6 mg/L during
      an embryo-larval test and 22.1 mg/L during the 28-day larval test.

PMID- 7726645
TI  - Dietary exposure of mink to carp from Saginaw Bay, Michigan. 1. Effects on
      reproduction and survival, and the potential risks to wild mink populations.
AB  - Carp (Cyprinus carpio) collected from Saginaw Bay, Michigan, containing 8.4 mg
      total polychlorinated biphenyls (PCBs)/kg and 194 ng of 2,3,7,8-tetrachloro
      dibenzo-p-dioxin equivalents (TEQs)/kg, were substituted for marine fish at
      levels of 0, 10, 20, or 40% in the diets of adult ranch mink (Mustela vison). The
      diets, containing 0.015, 0.72, 1.53, and 2.56 mg PCBs/kg diet, or 1.03, 19.41,
      40.02, and 80.76 ng TEQs/kg diet, respectively, were fed to mink prior to and
      throughout the reproductive period to evaluate the effects of a naturally
      contaminated prey species on their survival and reproductive performance. The
      total quantities of PCBs ingested by the mink fed 0, 10, 20, or 40% carp over the
      85-day treatment period were 0.34, 13.2, 25.3, and 32.3 mg PCBs/mink.
      respectively. The corresponding quantities of TEQs ingested by the mink over the
      same treatment period were 23, 356, 661, and 1,019 ng TEQs/mink, respectively.
      Consumption of feed by mink was inversely proportional to the PCB and TEQ content
      of the diet. The diet containing Saginaw Bay carp caused impaired reproduction
      and/or reduced survival of the kits. Compared to controls, body weights of kits
      at birth were significantly reduced in the 20 and 40% carp groups, and kit body
      weights and survival in the 10 and 20% carp groups were significantly reduced at
      three and six weeks of age. The females fed 40% carp whelped the fewest number of
      kits, all of which were stillborn or died within 24 hours. Lowest observable
      adverse effect levels (LOAEL) of 0.134 mg PCBs/kg body weight/day or 3.6 ng
      TEQs/kg body weight/day for adult female mink were determined. The potential
      effects of exposure of wild mink to contaminated Great Lakes fish were assessed
      by calculating "maximum allowable daily intakes" and "hazard indices" based on
      total concentrations of PCB residues in several species of Great Lakes fish and
      mink toxicity data derived from the study.

PMID- 7726646
TI  - Skeletal malformations induced by the insecticides ZZ-Aphox and Folidol during
      larval development of Rana perezi.
AB  - Tadpoles of Rana perezi were kept for 14 weeks in water containing two sublethal
      levels of the carbamate insecticide ZZ-Aphox or the organophosphate Folidol.
      Approximate concentrations of their active ingredients were 0.25 and 1 mg/L.
      Resulting malformations were studied by skeletal analysis and histological and
      histochemical investigation of te rear limbs of the tadpoles. The pesticides
      caused the animals to have malformations of the spinal column (scoliosis) and/or
      limbs (short and thick long bones with the epiphyses grossly twisted).
      Histochemical study showed differences in the composition of the connective
      matrix, and microscopic examination of the long bones indicated alterations in
      the thickness of the uncalcified bone matrix (osteoid) and the presence of
      abundant vascularised connective tissue in the region of the periosteum. The
      results confirmed changes in the composition of the connective tissue matrix as
      the cause of the defects observed in bone formation which are also discussed in
      relation to vitamin D absorption and calcium homeostasis.

PMID- 7726648
TI  - An evaluation of chemotherapy in patients with cancer of the cervix and lymph
      node metastases.
AB  - During the past twelve years, out of the 288 cervical cancer patients who had
      lymph node involvement, the recurrence rate in the lymph node, was 26.6% if one
      or two nodes were involved and 50.8% if three or more nodes were involved (P <
      0.0001). The recurrence rate of patients who received eight intravenous
      treatments (at monthly intervals) of multi-agent chemotherapy was lower than
      those who did not receive treatment. Of patients with one or two positive lymph
      nodes, 114 received treatment while 50 did not; their respective recurrence rates
      were 19.3% and 42.0%, a statistically significant difference (P < 0.025). Of
      patients with three or more positive lymph nodes, 97 received treatment and 27
      did not, their respective recurrence rates, were 46% and 66% (P = 0.30) and the
      difference is not statistically significant. It would seem that multi-agent
      chemotherapy may reduce the recurrence rate in patients with cancer of the cervix
      and positive lymph nodes.

PMID- 7726647
TI  - Genotoxic risk assessment of drinking water consumed in the city of Tehran, Iran.
AB  - Two hundred liters of drinking water of the city of Tehran were collected as tap
      water in a glass container and passed through a XAD-2 resin column at a flow rate
      of 60-100 ml/minute. The adsorbed materials were eluted with acetone, dried and
      dissolved in 2 ml dimethylsulfoxide (DMSO). Doses up to 10 microliters did not
      elevate sister chromatid exchanges (SCE) in CHO fibroblasts, while 20 microliters
      caused a significant increase in SCE. However, this dose did not show any
      chromosomal aberration (CA) in V79 fibroblasts. Doses up to 50 microliters of the
      extract did not increase his+ spontaneous revertant colonies in Salmonella
      typhimurium tester strain TA98, TA100 and TA102 in the absence of S9 metabolizing
      mixture, neither induced DNA alkaline labile sites in V79 fibroblasts.

PMID- 7726649
TI  - Peritoneal fluid volume and steroid hormone concentrations in baboons with and
      without either spontaneous minimal/mild endometriosis or the luteinized
      unruptured follicle syndrome.
AB  - This study was performed to document for the first time peritoneal fluid volumes
      and steroid hormone levels in baboons with and without endometriosis. A
      laparoscopy was carried out in 19 female baboons (11 with a normal pelvis and 8
      with histologically proven spontaneous minimal/mild endometriosis) during 64
      cycles in the early luteal phase. Peritoneal fluid was measured and aspirated.
      The pelvis was examined for evidence of recent ovulation and endometriosis.
      Peritoneal fluid and serum were assayed for 17 beta-estradiol and progesterone.
      The mean volume of peritoneal fluid and its concentration of 17 beta-estradiol
      and progesterone were 2.6 ml, 679 pmol/l and 64 nmol/l, respectively. No
      differences were observed between animals with or without either endometriosis or
      luteinized unruptured follicle syndrome. The peritoneal fluid and serum steroid
      levels were comparable to those found in women. The results presented are similar
      to those obtained in women with endometriosis and this suggests that the baboon
      can be used for the study of this disease.

PMID- 7726650
TI  - Influence of age and human papillomavirus-infection on reliability of cervical
      cytopathology.
AB  - The aim of the present study was to evaluate the effect of age and human
      papillomavirus (HPV) infection associated cellular changes on the predictive
      value of cervical cytology. In a group of 671 women with Papanicolaou smears
      suggesting low grade squamous intraepithelial lesion (LSIL), a high grade
      squamous intraepithelial lesion (HSIL) or invasive cervical cancer, cervical
      cytology was correlated with the histological finding. Predictive values were
      calculated and related to severity of the lesion, age and HPV associated changes.
      The predictive values of Papanicolaou (cervical) smears suggesting LSIL, HSIL and
      invasive carcinoma were 40%, 86%, and 78%, respectively. A poor predictive value
      of smears suggesting LSIL was found among older women. HPV associated changes
      were diagnosed in 80% of women < or = 25 years of age, 66% in the age group 26 to
      35 years, 51% in the age group 36 to 45 years and 38% in women aged > or = 46
      years (P = 0.03). The presence of HPV associated cellular changes led to a
      significantly higher number of overdiagnoses (9% with HPV infection compared to
      4% without HPV infection) and HPV negative cases were more frequently associated
      with underdiagnosis (15% without HPV infection compared to 8% with HPV infection,
      P = 0.0011). This result remained significant after adjustment for age (P =
      0.004). Cellular changes associated with HPV infection most frequently occurred
      in young women. HPV infection should therefore be acknowledged as source of
      overdiagnosis in the cytological evaluation of SIL especially in young women.

PMID- 7726651
TI  - Gemeprost for first trimester missed abortion.
AB  - In 87 patients with a missed abortion prior to 13 weeks, the application of a
      prostaglandin (PG) E1 derivative (1 mg gemeprost, Cergem) was compared to
      conventional surgical termination of pregnancy by cervical dilatation and
      curettage. In 33 patients with PGE1 application, complete expulsion of the
      abnormal pregnancy occurred after an average of 2.8 +/- 1.5 vaginal
      suppositories. PGE1 treatment was effective in 76.7%, and surgical management was
      effective in 90.9% of patients. Sixty percent of the patients in the PGE1 group
      required analgesia because of uterine pain in comparison to 4.5% in the surgical
      group. The possibility of medical termination with synthetic PG derivatives
      should be further investigated.

PMID- 7726652
TI  - Clomiphene citrate and phocomelia.

PMID- 7726653
TI  - Necrotizing fasciitis following postpartum tubal ligation. A case report and
      review of the literature.
AB  - Necrotizing fasciitis is a rare, but devastating subcutaneous bacterial infection
      which occurs following breaks in skin integrity, either natural, post traumatic
      or post surgical. Although it has been described following many surgical
      procedures, necrotizing fasciitis has not been previously described following
      postpartum tubal ligation. Necrotizing fasciitis was diagnosed four days after an
      uncomplicated postpartum tubal ligation via an infraumbilical incision. Rapid
      surgical debridement with broad spectrum antibiotic coverage provided successful
      therapy. Postpartum tubal ligation is one of the most common surgical procedures
      in obstetrics and gynecology, thus reports of complications resulting from this
      procedure are quite relevant to clinical practice. We present here the first
      reported case of necrotizing fasciitis following postpartum tubal ligation
      through an infraumbilical incision.

PMID- 7726654
TI  - Vaginitis emphysematosa during immunosuppressive therapy.
AB  - We report a case of vaginitis emphysematosa in an immunosuppressed renal
      transplant patient without detectable infection. Immunological factors may have
      been involved in the pathogenesis.

PMID- 7726655
TI  - A large hydatid cyst of the liver in pregnancy.
AB  - We report on a primigravida, who was admitted in the 14th week of pregnancy
      because of recurrent vomiting and upper abdominal pain. The diagnosis of a large
      20 cm echinococcal cyst of the liver was confirmed by ultrasound and an indirect
      hemagglutination test (IHA). In the 19th week of pregnancy a subtotal cystectomy
      was performed under perioperative treatment with the anthelmintic drug
      Albendazole. The patient delivered a 1420 g, 41 cm premature boy in breech
      position at 33 weeks. The significance of echinococcal cysts in pregnancy is
      discussed.

PMID- 7726656
TI  - Lysinuric protein intolerance in pregnancy: case report with successful outcome.
AB  - We present a 28-year-old pregnant woman who exhibited intolerance to lysinuric
      protein. However, she gave birth to a normal child without serious maternal
      complications. Since four of seven similar patients reported previously developed
      serious complications such as hemorrhage and eclampsia, patients with lysinuric
      protein intolerance are considered to be at high risk during pregnancy. A
      successful outcome can be achieved, provided that the anemia, thrombocytopenia,
      toxemia and hyperammonemia are well controlled.

PMID- 7726657
TI  - Relation between gestational sac diameter, crown-rump length, and maternal serum
      estradiol, progesterone, and prolactin levels in early pregnancy.
AB  - In 152 patients with an early pregnancy which was subsequently normal, we
      measured the maternal serum levels of estradiol (E2), progesterone (P4) and
      prolactin (PRL) as well as the diameter of gestational sac (GS) and the crown
      rump length (CRL) of the embryo by transvaginal ultrasonography. The maternal
      serum level of E2 had the closest statistically significant correlation with both
      the GS diameter (r = 0.769, P < 0.01) and the CRL (r = 0.736, P < 0.001). P4 and
      PRL concentrations showed less correlation with embryo development.

PMID- 7726658
TI  - Serial fetal heart rate monitoring in monozygotic twin, one of which was
      anencephalic.
AB  - This report describes FHR patterns of monozygotic twins, one of whom was
      anencephalic. The recording were made from 20 to 36 weeks of gestation.
      Differences were observed in the FHR patterns after week 28.

PMID- 7726659
TI  - A study of serum CASA and CA 125 levels in patients with ovarian carcinoma.
AB  - The assays of Cancer Associated Serum Antigen (CASA) and CA 125 were assessed in
      the management of patients with ovarian cancer. It was shown that CASA is
      sensitive to ovarian carcinoma, and both CASA and CA 125 are more useful when
      used in conjunction.

PMID- 7726660
TI  - Multi drug resistant tuberculosis: what will happen in developing countries?

PMID- 7726661
TI  - [Prospective reflections on malaria field research].

PMID- 7726662
TI  - [Relationship between Plasmodium parasitemia and febrile episodes in various
      population groups in Kinshasa, Zaire].
AB  - The objective of this study was to determine the relative importance of
      determinants of fever-episodes in an environment with perennial malaria
      transmission. In 6 neighbourhoods of Kinshasa with different degrees of
      urbanization, 120 clusters of children younger than 10 years were selected over a
      one year period and followed up for 2 weeks each. In the 4,816 children retained
      for analysis 906 fever episodes were registered, which corresponds to an average
      incidence rate of 4.9 episodes per child per year. Seven hundred (77.3%) of the
      fever cases had a positive thick film (IF) but of the 3,289 children with a
      positive TF only 21.3% presented fever during the observation period.
      Nevertheless, high parasite densities formed, without neglecting the role of
      other infectious etiologies, the mayor pathogenic mechanism associated with
      fever. The risk for a fever episode was, in multivariate analysis, 40 times
      higher in children with at least one positive TF than in children with a negative
      TF on both day 1 and day 14, and amongst the ones with a positive TF the risk was
      3 times higher in children with a parasitemia above 3,000 trophozoites/microliter
      blood. The habitat constituted another important independent determinant: the
      relative risk for fever was 1.48 for non-urbanized neighbourhoods, which probably
      reflects the low malaria transmission in the urbanized ones, but 2.1 for semi
      urbanized against peripheral neighbourhoods, where the parasite index is high.
      Low socio-economic status, the short dry season and young age formed, in this
      order, further factors to the take into account.

PMID- 7726663
TI  - [Diagnostic and therapeutic management of uncomplicated malaria attacks in the
      Dakar region, Senegal].
AB  - A questionnaire survey was conducted in the Dakar region (Senegal) between August
      and October 1992 to investigate diagnosis and treatment practices for
      uncomplicated malaria attacks in the health care facilities. The sample consisted
      of 208 prescribers in the operational sense i.e. 20% of the following
      professional categories: medical doctors, health care technicians, birth
      attendants, qualified nurses, and auxiliary nurses. A thick smear was mentioned
      as a diagnostic element by 23% of the practitioners; chloroquine remained the
      first choice drug for 80% of the personnel but 13% declared prescribing
      parenteral quinine for uncomplicated malaria in patients without vomiting;
      halofantrine and the association sulfadoxine-pyrimethamine-mefloquine are
      prescribed by respectively 7 and 1% of the personnel, also in the public sector;
      chloroquine is prescribed in an effective dose (25-40 mg/kg) by 74% of the
      personnel for adults and by 43% for children; quinine base in a dose below 25
      mg/kg by 100% of personnel for adults and by 99% for children; nearly half of the
      prescribers do not take into account the children's weight; 13% of the
      practitioners prescribe useless expensive symptomatic treatments and 45 to 73%
      ignore the price of the common antimalarials, allowing for a 10% error; health
      care workers have a bad knowledge of the results of chemosensitivity surveys. The
      development of a national malaria control programme that emphasises permanent
      training of the health care workers and control of therapeutic information seems
      mandatory.

PMID- 7726664
TI  - Epidemic schistosomiasis in the delta of the Senegal River Basin, Senegal:
      responses of the health care system.
AB  - Since 1988, the delta of the Senegal River Basin has experienced an exceptional
      epidemic of intestinal schistosomiasis, following the development of large
      irrigation projects. Urinary schistosomiasis was also rapidly spreading. The
      response of the health care system to the epidemics is described. Control was
      integrated in the existing health care system, according to the general health
      policy of Senegal. Control was based on passive detection, treatment, health
      education and information. The availability of praziquantel was assured. Priority
      was given to the development of health services in general. Initial reports have
      also attracted different research groups to the area. The variety of
      epidemiological situations made this area unique for research. Researchers would
      like to observe untreated communities to study the development of immune
      mechanisms. Inevitably such approach must lead to confrontation with local health
      services which should offer ethically and medically correct management of
      infected individuals and affected communities.

PMID- 7726665
TI  - [Diagnosis of anemia at high altitude: problems encountered in Tibet].
AB  - To test the hypothesis that Tibetans do not increase their haemoglobin
      concentration with increasing altitude, haemoglobin concentrations of children
      aged 6 to 72 months were analyzed. The mean haemoglobin concentrations in the
      different age groups are significantly lower than the mean concentrations
      expected at this altitude. Histograms and tests for normality show that the
      haemoglobin distributions are Gaussian. The probability plots confirm the
      coefficients of skewness, which indicate a superimposed subpopulation towards the
      lower range of haemoglobin values. A mixed distribution analysis identifies that
      the curvilinear deviation found in the probability plot encompasses 10 to 12% of
      the studied population. Together with the normality of the haemoglobin
      distributions, we are led to suppose that this is the anaemic population. These
      figures are considerably lower than those found using recommended cut-off values
      for this altitude; 40 and 46%. Two possible explanations are put forward: 1) the
      whole population is submitted to the same factor and hence the whole population
      should be considered anaemic, 2) Tibetans react differently to altitude than
      other mountain people and have adapted themselves without increase in
      haemoglobin.

PMID- 7726666
TI  - [Aedes albopictus and Aedes aegypti at Ile de la Reunion].
AB  - Aedes albopictus and Aedes aegypti are both found on the island. The former,
      being the probable vector of dengue on the island, is highly anthropophilic. It
      breeds in domestic environments as well as in natural breeding sites. The latter
      has a more restricted distribution and is never anthropophilic. Larvae of Ae.
      aegypti are only found in natural habitats, always associated with Ae.
      albopictus, but in small proportions. Such an ecology and behaviour for the
      typicus form of Ae. aegypti are abnormal. Several hypothetic explanations are
      proposed. Dengue prevention should be based solely on Ae. albopictus control.

PMID- 7726667
TI  - Cost of drugs at an urban primary health care centre in Alexandra, South Africa.
AB  - This report provides an analysis of expenditure on pharmaceuticals at the
      Alexandra Health Centre and University Clinic (AHC), South Africa. Drug costs
      increased at a rate higher than for the general expenditure budget. The drug cost
      per script per department varied from R9.43 for patients attending the diabetic
      clinic to R0.60 for antenatal care patients. In general, female consultations at
      the adult outpatient department (AOPD) were more expensive than male's and
      adult's more than paediatric's. The largest share of drug costs went to adult
      female patients in AOPD and the smallest share went into preventive and promotive
      care services. Again the same observations apply for drug costs as percentage of
      the total costs per clinical department. This study shows that drug costs were a
      significant contributor to the level of primary health care (PHC) expenditure. We
      discuss the alternatives to cost-recovery in a concrete situation like the peri
      urban community being served by the AHC. It is concluded that in communities
      similar to Alexandra it would be possible to provide PHC at about R30 per capita
      per annum with about 15% being spent on pharmaceuticals.

PMID- 7726668
TI  - On enteral nutrition during multimodality therapy in upper gastrointestinal
      cancer patients.

PMID- 7726669
TI  - Enteral nutrition during multimodality therapy in upper gastrointestinal cancer
      patients.
AB  - OBJECTIVE: The objective of this study was to evaluate long-term enteral
      nutrition support in postoperative cancer patients. BACKGROUND: Multimodality
      therapy for surgical patients with upper gastrointestinal malignancies may
      improve survival, but often results in substantial malnutrition,
      immunosuppression, and morbidity. The benefits of combined inpatient and
      outpatient enteral feeding with standard diets or diets supplemented with
      arginine, RNA + omega-3 fatty acids are unclear. METHODS: Sixty adult patients
      with esophageal (22), gastric (16), and pancreatic (22) lesions were stratified
      by disease site and percent usual weight and randomized to receive supplemental
      or standard diet via jejunostomy beginning on the first postoperative day (goal =
      25 kcal/kg/day) until hospital discharge. Patients also were randomized to
      receive (n = 37) or not receive (n = 23) enteral jejunostomy feedings (1000
      kcal/day overnight) for the 12- to 16-week recovery and radiation/chemotherapy
      periods. Plasma and peripheral white blood cells were obtained for fatty acid
      levels and PGE2 production measurements. RESULTS: Mean plasma and cellular omega
      3/omega 6 fatty acid levels (percent composition) increased significantly (p <
      0.05) in the arginine + omega-3 fatty acid group by postoperative day 7 (0.30 vs.
      0.13) and (0.29 vs. 0.14) and continued to increase over time. Mean PGE2
      production decreased significantly (p < 0.05) from 2760 to 1600 ng/10(6) cells/mL
      at day 7 in the arginine + omega-3 fatty acid group, whereas no significant
      change over time was noted in the standard group. Infectious/wound complications
      occurred in 10% of the supplemented group compared with 43% of the standard group
      (p < 0.05); mean length of hospital stay was 16 vs. 22 (p < 0.05) days,
      respectively. Of the patients who received postoperative chemoradiation therapy,
      only 1 (6%) of the 18 patients randomized to receive tube feeding did not
      continue, whereas 8 (61%) of the 13 patients not randomized to tube feedings
      required crossover to jejunostomy nutritional support. CONCLUSIONS: Supplemental
      enteral feeding significantly increased plasma and peripheral white blood cell
      omega 3/omega 6 ratios and significantly decreased PGE2 production and
      postoperative infectious/wound complications compared with standard enteral
      feeding. For outpatients receiving adjuvant therapy, those initially randomized
      to oral feedings alone required rehospitalization more frequently, and 61%
      crossed over to supplemental enteral feedings.

PMID- 7726670
TI  - Duodenum-preserving resection of the head of the pancreas in chronic
      pancreatitis. A prospective, randomized trial.
AB  - OBJECTIVE: Two techniques of duodenum-preserving resection of the head of the
      pancreas were compared in a prospective, randomized trial. The technical
      feasibility and effects on quality of life were assessed. SUMMARY BACKGROUND
      DATA: Drainage and resection are the principles of surgery in chronic
      pancreatitis. The techniques of duodenum-preserving resection of the head of the
      pancreas as described by Berger and Frey combine both to different degrees. The
      efficacy of both procedures has not been compared thus far. METHODS: Forty-two
      patients were allocated randomly to either Beger's (n = 20) or Frey's (n = 22)
      group. In addition to routine pancreatic diagnostic work-up, a multidimensional
      psychometric quality-of-life questionnaire and and a pain score were used.
      Assessment of endocrine and exocrine function included oral glucose tolerance
      test, serum concentrations of insulin, C-peptide, and HbA1c, as well as fecal
      chymotrypsin and pancreolauryl test. The interval between symptoms and surgery
      ranged from 12 months to 12 years, with a mean of 5.7 years. The mean follow-up
      was 1.5 years. RESULTS: There was no mortality. Overall morbidity was 14% (20%
      Beger, 9% Frey). Complications from adjacent organs were resolved definitively in
      94% (90% Beger, 100% Frey). A decrease of 95% and 94% of the pain score after
      Beger's and Frey's procedure, respectively, and an increase of 67% of the overall
      quality-of-life index in both groups were observed. Endocrine and exocrine
      function did not differ between both groups. CONCLUSIONS: Both techniques of
      duodenum-preserving resection of the head of the pancreas are equally safe and
      effective with regard to pain relief, improvement of quality of life, and
      definitive control of complications affecting adjacent organs. Neither procedure
      leads to further deterioration of endocrine and exocrine pancreatic function.

PMID- 7726671
TI  - Study of surgical anatomy for duodenum-preserving resection of the head of the
      pancreas.
AB  - OBJECTIVE: The authors precisely examined the topography of the duodenum,
      pancreas, bile duct, and supplying vessels from the perspective of performing
      duodenum-preserving resection of the pancreatic head. SUMMARY BACKGROUND DATA:
      Little has been reported regarding the detailed surgical anatomy that is crucial
      in this procedure. METHODS: The authors precisely examined the local anatomy of
      the pancreas head and duodenum, using materials from 40 autopsy cases. RESULTS:
      Arcade formation between the anterior superior pancreaticoduodenal (ASPD) artery
      and the anterior inferior pancreaticoduodenal (AIPD) artery was found in all of
      the cases. After departing from the gastroduodenal artery, the ASPD ran toward a
      point 1.5 cm below the papilla of Vater, then turned to the posterior aspect of
      the pancreas to joint the AIPD. In 88% of the cases, an arcade was found between
      the posterior superior pancreaticoduodenal (PSPD) artery and the posterior
      inferior pancreaticoduodenal (PIPD) artery. The ASPD, AIPD, PSPD, PIPD, or their
      branches to the duodenum, the bile duct, and the papilla of Vater were not
      completely buried in the pancreatic parenchyma in any of these cases. Generally,
      it was easy to dissect the pancreas from the duodenum because of the loose
      connection. Near the accessory papilla, however, dissection of the vessels was
      difficult, and the pancreatic parenchyma sometimes was found in the wall of the
      duodenum. Dissection of the pancreas from the common bile duct and identification
      of the main pancreatic duct at the junction with the terminal portion of the bile
      duct were straightforward in all cases. CONCLUSIONS: It may be possible to remove
      the head of the pancreas while preserving of the vascular arcades and their
      branches to the duodenum, the bile duct, and the papilla of Vater.

PMID- 7726672
TI  - General stress response to conventional and laparoscopic cholecystectomy.
AB  - OBJECTIVE: In many retrospective and prospective observational studies,
      laparoscopic cholecystectomy (LC) compares favorably with conventional
      cholecystectomy (CC), with respect to length of hospital stay, postoperative
      pain, and pulmonary function, indicating a diminished operative trauma.
      Comparison of laboratory findings (stress hormones, blood glucose, interleukins)
      are a possibility to objectify stress and tissue trauma of laparoscopic and
      conventional cholecystectomy. SUMMARY BACKGROUND DATA: Major body injury,
      surgical or accidental, evokes reproducible hormonal and immunologic responses.
      The magnitude of many of these changes essentially is proportional to the extent
      of the injury. METHODS: In a prospective study, biochemical stress parameters
      were measured in the blood of patients undergoing elective cholecystectomy
      because of symptomatic cholecystolithiasis. Patients with acute cholecystitis,
      pancreatitis, choledocholithiasis, or malignant disease were excluded. Values
      from 40 patients after LC and from 18 patients after CC were compared. Both
      groups had similar patient characteristics, baseline values, and perioperative
      care, except for deeper anesthesia during CC. RESULTS: On postoperative day 1,
      epinephrine (p = 0,05), norepinephrine (p = 0.02), and glucose (p = 0.02)
      responses were higher after CC. Two days postoperatively, norepinephrine remained
      higher after CC (p < 0.01). Interleukin-1 beta responses were higher during (p <
      0.01) and 6 hours after CC (p = 0.03). Interleukin-6 responses were higher 6
      hours (p = 0.03), 1 day (p = 0.02), and 2 days (p < 0.01) after CC. CONCLUSIONS:
      The results show significant lower values of intraoperatively and postoperatively
      measured epinephrine, norepinephrine, interleukin-1 beta, and interleukin-6 in
      patients with laparoscopic cholecystectomy, indicating a minor stress response
      and tissue trauma in this group of patients. The results correspond to the
      favorable results of most other trials evaluating clinical aspects of
      laparoscopic cholecystectomy.

PMID- 7726673
TI  - Multivariate comparison of complications after laparoscopic cholecystectomy and
      open cholecystectomy.
AB  - OBJECTIVE: To answer the question whether laparoscopic cholecystectomy (LC) or
      open cholecystectomy (OC) is safer in terms of complications, the authors
      evaluated complications relating to 1440 cholecystectomies performed by the same
      surgeons in a retrospective study. SUMMARY BACKGROUND DATA: A definite
      pronouncement on whether LC truly is superior to OC is not possible because
      prospective trials are burdened with problems of recruitment. METHODS: After the
      introduction of LC at the authors' institution in April 1991 and until October
      1993, 94.6% (700/740) of all patients admitted for operation because of
      symptomatic gallstone disease could be treated laparoscopically. The clinical
      records of the last 700 patients who underwent OC before the introduction of LC
      were re-evaluated with regard to both overall complications and the grade of
      complication (severity grade 1-4). A comparison of the incidence of complications
      relating to the two surgical methods, age, sex, common bile duct stones, acute
      cholecystitis, concomitant illness, Apache score, and length of operation was
      calculated by multivariate analysis using the logistic regression model. RESULTS:
      The total rate of complications in the OC group was 7.7%, with five postoperative
      deaths, compared with 1.9% and one postoperative death in the LC group.
      Multivariate analysis for OC revealed that both old age (p = 0.014) and the
      existence of common bile duct stones (p = 0.02) had independent prognostic
      influences in increasing the overall complication rate, whereas only old age (p =
      0.019) influenced the overall complication rate after LC. Multivariate analysis
      of all cholecystectomies (n = 1440) showed that the overall complication rate was
      influenced independently by OC as a detrimental factor. CONCLUSIONS: As this
      analysis emphasizes, LC can be performed safely with an overall complication rate
      that is distinctly lower than that of OC. For selective surgery, LC is
      undoubtedly superior to OC and can probably be seen as a new "gold standard" for
      cholecystectomies.

PMID- 7726674
TI  - Gastrogastric fistulas. A complication of divided gastric bypass surgery.
AB  - OBJECTIVE: This report warns that gastrogastric fistulas may follow the division
      of the stomach in bariatric surgery. SUMMARY BACKGROUND DATA: Although surgery is
      the most effective therapy for morbid obesity, the procedures are still
      undergoing evolution. One of the key elements in bariatric surgery is the
      partition of the stomach to develop a much smaller reservoir. The partition has
      been done with single layers of staples with almost universal failure and with
      double layers of staples with a failure rate of 11.8% when observed for a 12-year
      follow-up. METHODS: This report details the experience with a series of 100
      consecutive patients in whom the partition was created by dividing the stomach.
      RESULTS: The course of six patients was complicated by gastrogastric fistulas.
      One of the patients had the gastric bypass as the initial bariatric operation; in
      the other five, the gastric bypasses were carried out to revise failed staple
      lines. Although one of the patients required drainage for a subphrenic abscess,
      two had only self-limited signs of infection. In the remaining three patients,
      there was no evidence of any complication. CONCLUSION: Gastrogastric fistulas
      followed division of the stomach in 6% of our gastric bypass operations. Methods
      for avoiding this complication include oversewing staple lines, using strong
      bites of tissue during the anastomosis, avoiding obstruction of the Roux-en-Y
      jejunal segment, and testing of the integrity of the anastomosis with methylene
      blue dyes. The ideal method for partition of the stomach remains to be developed.

PMID- 7726675
TI  - Hepatic metastases from soft-tissue sarcoma.
AB  - OBJECTIVE: Hepatic metastases from soft-tissue sarcoma are evaluated to define
      treatment and its limitations. METHODS: From 981 adult patients with diagnoses of
      soft-tissue sarcoma, 65 patients with hepatic metastases were studied. RESULTS:
      An intra-abdominal primary site was present in 61 of 65 patients, with 85% high
      grade leiomyosarcoma. Hepatic resection was performed in 14 patients (22%). All
      patients have had recurrences after hepatic resection-11 of 14 in the liver--with
      a median survival of 30 months. Chemotherapy resulted in partial response in
      three patients and no complete responses. Survival is not influenced by grade,
      type, primary site, disease-free interval, chemotherapy, or hepatic resection.
      CONCLUSIONS: The uncommon response to conventional chemotherapy does not support
      its use in the treatment of hepatic metastases from soft-tissue sarcoma. Extent
      of disease limits the application and success of hepatic resection for soft
      tissue sarcoma, and anything less than complete resection is not indicated.

PMID- 7726676
TI  - Pathogenesis of hemorrhage-induced bacteria/endotoxin translocation in rats.
      Effects of recombinant bactericidal/permeability-increasing protein.
AB  - OBJECTIVES: This study was conducted to determine the role of gut-derived
      bacteria/endotoxin in the pathogenesis of the multiple-organ damage and
      mortality, the possible beneficial effect of recombinant
      bactericidal/permeability-increasing protein (rBPl21), and whether neutralizing
      endotoxemia by rBPl21 treatment influences tumor necrosis factor (TNF) formation
      in rats after hemorrhagic shock and resuscitation. SUMMARY BACKGROUND DATA:
      Hypovolemic shock might be associated with bacterial or endotoxin translocation
      as well as systemic sepsis. Similar to bactericidal/permeability-increasing (BPl)
      protein, rBPl21 has been found to bind endotoxin and inhibit TNF production.
      METHODS: A rat model of prolonged hemorrhagic shock (30 to 35 mm Hg for 180 min)
      followed by adequate resuscitation was employed. Recombinant
      bactericidal/permeability-increasing protein was administered at 5 mg/kg
      intravenously. The control group was treated similarly to the BPl group, but
      received thaumatin as a protein-control preparation in the same dose as rBPl21.
      RESULTS: Immediately after resuscitation (230 min), plasma endotoxin levels in
      the control group (61.0 +/- 16.3 pg/mL) were almost neutralized by rBPl21
      treatment (13.8 +/- 4.8 pg/mL, p < 0.05). Plasma TNF levels were not
      significantly influenced by rBPl21 treatment. The 48-hour survival rate was 68.8%
      in the treatment group versus 37.5% in the control group (p = 0.08). Microscopic
      histopathologic examination revealed relatively minor damage to various organs in
      the treatment group. CONCLUSIONS: These data suggest that hemorrhagic shock may
      lead to bacterial/endotoxin translocation with concomitant TNF formation,
      endogenous endotoxemia may play an important role in the pathogenesis of multiple
      organ failure after shock and trauma, TNF formation at an early stage might be
      related mainly to mechanisms other than Kupffer's cells activation via
      lipopolysaccharide, and rBPl21 might be a useful therapeutic agent against
      endogenous bacteria/endotoxin related disorders in severe hemorrhagic shock.

PMID- 7726677
TI  - Short- and long-term outcomes of kidney transplants with multiple renal arteries.
AB  - OBJECTIVE: The authors determined whether the use of kidney allografts with
      multiple renal arteries adversely effects post-transplant graft and patient
      outcome or increases the incidence of vascular and urologic complications.
      BACKGROUND: Kidney grafts with multiple renal arteries have been associated with
      an increased incidence of early vascular and urologic complications. Kidney
      transplants with single versus multiple renal arteries have not been compared in
      regard to long-term graft and patient outcome or post-transplant incidence of
      hypertension, acute tubular necrosis, rejection, and late vascular and urologic
      complications. METHODS: We analyzed 998 adult kidney transplants done from
      December 1, 1985 through June 30, 1993, in which only the recipient's external or
      internal iliac artery was used for anastomosis. We divided the study population
      into 3 groups: Group A-1 renal artery, 1 arterial anastomosis (n = 835), Group B-
      >1 renal artery, 1 arterial anastomosis (n = 112), Group C-->1 renal artery, > 1
      arterial anastomosis (n = 51). We compared the incidence of post-transplant
      hypertension, acute tubular necrosis, acute rejection, and vascular and urologic
      complications; mean creatinine levels at 1, 3, and 5 years post-transplant; and
      patient and graft survival. Univariate and multivariate analyses were done to
      identify risk factors for vascular complications. RESULTS: We found no
      significant differences among the three groups for the following variables: post
      transplant hypertension, acute tubular necrosis, acute rejection, creatinine
      levels, early vascular and urologic complications, and graft and patient
      survival. In kidneys with single arteries, the presence (vs. absence) of an
      aortic patch and the type of the arterial anastomosis (end-to-end to the
      hypogastric vs. end-to-side to the external iliac artery) did not have an impact
      on the incidence of early or late vascular complications. In kidneys with
      multiple arteries, only the rate of late renal artery stenosis was higher, the
      rate of early vascular and urologic complications was not different. Our
      multivariate analysis identified acute tubular necrosis as a risk factor for
      renal artery and vein thrombosis; graft placement on the left side for arterial
      thrombosis; and preservation time > or = 24 hours and multiple renal arteries for
      renal artery stenosis. CONCLUSIONS: Results of kidney transplants using
      allografts with multiple versus single arteries are similar.

PMID- 7726678
TI  - Surgical management of cardiac pheochromocytoma. Resection versus
      transplantation.
AB  - OBJECTIVE: The authors review their experience and that of others who have
      reported cases in the literature on the surgical management of cardiac
      pheochromocytomas. SUMMARY BACKGROUND DATA: Cardiac pheochromocytomas are rare
      cathecolamine-producing tumors that can be densely adherent to myocardium.
      Because resection can be associated with significant morbidity, we sought to
      determine the best mode of treatment for these difficult tumors. METHOD: The
      authors reviewed the experience for management of cardiac pheochromocytomas in
      their two institutions and those reported in the literature. Follow-up was
      available for 21 of 26 patients up to 9 years after resection. RESULTS: Twenty
      five patients had reconstruction of the native heart; five (20%) died
      intraoperatively from hemorrhage, one (4%) died postoperatively from sepsis,
      three (12%) sustained myocardial infarction, one (4%) required a mitral valve
      replacement, and three (12%) had incomplete resections, two of whom subsequently
      developed metastatic disease and died. One patient, thought to be a high risk for
      resection, received an orthotopic heart transplantation. CONCLUSIONS: Surgical
      resection of cardiac pheochromocytomas can be performed successfully. However,
      resection of lesions that aggressively invade adjacent myocardium is associated
      with significant mortality and inadequate control of the neoplasm. Cardiac
      transplantation should be available as an option before embarking on resection,
      and it should be performed if mandated by intraoperative findings.

PMID- 7726679
TI  - Glutamine enhances selectivity of chemotherapy through changes in glutathione
      metabolism.
AB  - OBJECTIVE: Chemotherapy doses are limited by toxicity to normal tissues.
      Intravenous glutamine protects liver cells from oxidant injury by increasing
      intracellular glutathione (GSH) content. The authors hypothesized that
      supplemental oral glutamine (GLN) would increase the therapeutic index of
      methotrexate (MTX) by improving host tolerance through changes in glutathione
      metabolism. The authors examined the effects of oral glutamine on tumor and host
      glutathione metabolism and response to methotrexate. METHODS: Thirty-six 300-g
      Fischer 344 rats were implanted with fibrosarcomas. On day 21 after implantation,
      rats were randomized to receive isonitrogenous isocaloric diets containing 1
      g/kg/day glutamine or glycine (GLY) by gavage. On day 23 after 2 days of
      prefeeding, rats were randomized to one of the following four groups receiving an
      intraperitoneal injection of methotrexate (20 mg/kg) or saline (CON): GLN+MTX,
      GLY+MTX, GLN-CON, or GLY-CON. On day 24, rats were killed and studied for
      arterial glutamine concentration, tumor volume, kidney and gut glutaminase
      activity, and glutathione content (tumor, gut, heart, liver, muscle, kidney, and
      lung). RESULTS: Provision of the glutamine-enriched diets to rats receiving MTX
      decreased tumor glutathione (2.38 +/- 0.17 in GLN+MTX vs. 2.92 +/- 0.20 in
      GLY+MTX, p < 0.05), whereas increasing or maintaining host glutathione stores (in
      gut, 2.60 +/- 0.28 in GLN+MTX vs. 1.93 +/- 0.18; in GLY+MTX, p < 0.05). Depressed
      glutathione levels in tumor cells increases susceptibility to chemotherapy.
      Significantly decreased glutathione content in tumor cells in the GLN+MTX group
      correlated with enhanced tumor volume loss (-0.8 +/- 1.0 mL in GLN+MTX vs. +9.5
      +/- 2.0 mL in GLY+MTX, p < 0.05). CONCLUSION: These data suggest that oral
      glutamine supplementation will enhance the selectivity of antitumor drugs by
      protecting normal tissues from and possibly sensitizing tumor cells to
      chemotherapy treatment-related injury.

PMID- 7726680
TI  - Long-term results of subtotal esophagectomy with three-field lymphadenectomy for
      carcinoma of the thoracic esophagus.

PMID- 7726681
TI  - Are elevated liver enzymes and bilirubin levels significant after laparoscopic
      cholecystectomy in the absence of bile duct injury?

PMID- 7726682
TI  - Overexpression of p53 and HER-2/neu proteins as prognostic markers in early stage
      breast cancer.

PMID- 7726683
TI  - Treatment of breast cancer.

PMID- 7726684
TI  - [Nuclear cardiology in the pediatric patient].

PMID- 7726685
TI  - [The effects of digitalis compounds on K(+)-induced relaxation in aortic rings].
AB  - It has been shown that, changes in the structure of the cardiac glycoside, are
      related to changes in their biological effects. In the present study we compared
      the effects of two structurally different digitalis compound (ouabain and
      ouabagenin), on K+ induced vascular relaxation as an index of the Na+K+ ATPase
      activity. Ouabain was the most potent compound tested, and had vasoconstrictor
      effect on the rat aortic rings, as, well as inhibitory effect on the K(+)-induced
      relaxation. Ouabagenin did not affect either the vascular tone or K(+)-induced
      relaxation. It is well known that changes in the part of the structure of the
      cardiac glycoside that contain the sugar, are important to maintain some of their
      biological effects. In this paper we demonstrate that elimination of the 1
      rhamnose in ouabagenin reduces its vascular effects associated to the inhibition
      of the Na+ K+ ATPase pump.

PMID- 7726686
TI  - [A morphometric study of the right ventricular infundibulum in complete
      transposition of the great arteries].
AB  - To demonstrate that the right ventricular infundibulum changes its spatial
      orientation in hearts with complete transposition of the great arteries, sixty
      five hearts with this malformation, with anterior and right sided aorta were
      studied morphometrically. The inlet apex and infundibular arises in the right
      ventricule were interrelated. The angles formed by the intersection of both
      arises were measured, and the results were compared with those obtained from a
      similar study in thirty five normal hearts. The angles obtained in the hearts
      with transposition of the great arteries were of 156.5 degrees, and those
      measured in the normal hearts were of 126.6 degrees. This difference was
      interpreted as an indicator of a vertical shift of the right ventricular
      infundibulum toward the right, to the same side in which the aorta is located and
      with which it is connected. In this way this outlet looses its leftward direction
      observed in normal hearts. It is concluded that although complete transpositions
      of the great arteries developmentally has its origin primarily in the truncus of
      the embryonic heart, the infundibulum is also involved modifying its position.

PMID- 7726687
TI  - [The late follow-up evolution of myocardial infarct].
AB  - The aim of this paper was to study the long term evolution of patients (one to
      five years) after an acute myocardial infarction. Three hundred and twenty
      questionnaires were sent to patients admitted and diagnosed as acute myocardial
      infarction in the private sector of the Instituto Nacional de Cardiologia
      "Ignacio Chavez". One hundred seventy five useful answers were obtained. Of these
      patients, coronariography was performed in 132 during the acute episode. In 57
      CABG was performed. Most of them had three vessels or main left coronary artery
      occlusions. In the late long term evolution 68 patients had angor pectoris, 16
      had unstable angina, more advanced lesions were found in 14 of them in a new
      angiographic study. In nine CABG was performed, three were treated with
      angioplasty, in two there was no indication for intervention. One had a new
      myocardial infarction and one died. Only four patients had a new myocardial
      infarction, two of them died, and another one had heart failure. In three of them
      a new angiographic study showed significant occlusion of the main left coronary
      artery. Eight patients died between the second and fourth year of evolution, in
      two it was a sudden death, two had a new myocardial infarction, three had heart
      failure and in one the cause of death was a stroke. Ten patients died during the
      first year of evolution the main cause was sudden death.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7726688
TI  - [The first myocardial infarct in the elderly patient].
AB  - Acute myocardial infarction (AMI) in patients over 65 years of age represent more
      than half of the patients with AMI. Among them, between 60 and 80% represent the
      first AMI. The objective of this study is to evaluate the behavior of AMI in this
      group of patients. The clinical charts of patients over 65 years of age with
      ischemic heart disease admitted into the hospital during the past two years, were
      reviewed. We used the international criteria (clinical, ECG, enzymatic,
      echocardiographic and scintigraphic studies) for the diagnosis of AMI. Patients
      with previous AMI were excluded. We included 274 patients (68% males and 32%
      females). The age varied from 65 to 91 years with an average of 71.7 +/- 5.3
      years. Typical symptoms were present in 90.5% and atypical in 9.5% of the cases,
      being the latest most frequent in those over 75 years of age. RISK FACTORS:
      cigarette smoking was present in 60% of the patients, hypertension in 52% and
      diabetes mellitus in 37%. Both of them were associated in 21%. In 144 cases
      (52.5%) the MI localization was anterior and in 130 (47.5%) inferior; among them
      47 patients (36%) had extension to the right ventricle and 7 (2.5%) had a non Q
      AMI. COMPLICATIONS: Type I-II VPCs of Bernard Lown were present in 18% and type V
      10.2%. Compete AV block in 14.2% (all of them with inferior wall MI);
      bifascicular block in 55 and mitral insufficiency due to papillary muscle
      dysfunction in 6.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726689
TI  - [Percutaneous mitral valvuloplasty with the Inoue balloon. The initial experience
      and 3-year clinical follow-up at the Instituto Nacional de Cardiologia Ignacio
      Chavez].
AB  - In 113 patients with mitral stenosis a balloon mitral valvuloplasty (VMPB) was
      performed. There were 97 female and 16 male patients. Mean age was 40 +/- 11 with
      range of 18 and 70 years. 95 patients had sinus rhythm and 18 were on atrial
      fibrillation. Previous mitral commissurotomy was reported in 13 patients and 5
      were pregnant at the moment of the procedure. Patients were carefully selected
      using both clinical and echocardiographic studies as well as the Wilkins score
      (SW). Transesophageal echocardiography (ETE) was performed when transthoracic
      echocardiography was not satisfactory. After right and left catheterization, VMPB
      was performed. In 106 patients (93.8%) a significant increase of the area mitral
      valve (AVM) was obtained. Echocardiographic results showed an AVM increase from
      0.95 +/- 0.19 to 1.61 +/- 0.34 cm2 (p < 0.0001). Mean mitral gradient (GTM)
      decreased from 16.18 +/- 4.69 to 9.14 +/- 3.2 mmHg (p < 0.0001). Functional class
      improved in all patients in the long term. As complications there was severe
      mitral regurgitation (IM) reported in 6 patients who subsequently underwent
      mitral valve exchange, 2 of then died during surgery (one of them by bleeding and
      the other by non reparable rags on the atrium). A patient had cerebrovascular
      event (EVC) one week after the VMPB. In 3 of them non-significant interatrial
      communication (CIA) was produced. One patient died two months after the procedure
      due to bacterial endocarditis (EBSA). VMPB can be considered as a safe and
      effective treatment to patients with mitral stenosis.

PMID- 7726690
TI  - [Ventricular aneurysm in chronic Chagas' disease. The experience of the Instituto
      Nacional de Cardiologia Ignacio Chavez].
AB  - This work describes the incidence of ventricular aneurysms in patients with
      angiographically normal epicardial coronary arteries, who have epidemiological,
      clinical and serologic features suggesting chronic Chagasic cardiomyopathy
      (C.C.C). Eight out of 22 patients (36%) with such features had ventricular
      aneurysm. Three were located on the apex, 3 anteroapical and 2 basal. All
      patients had arrhythmia. In a case it was necessary a surgical approach to
      control a medically intractable life threatening ventricular tachyarrhythmia. In
      regard of the incidence of ventricular aneurysms in C.C.C., our results are in
      agreement with published experiences in South America. Surgical treatment of
      chagasic aneurysm should be considered when medical treatment is unable to
      control dangerous arrhythmia and an electrophysiological study supports this
      approach.

PMID- 7726691
TI  - [Lipoprotein(a) in heterozygote familial hypercholesterolemia].
AB  - Familial hypercholesterolemia (FH) is the genetic lipid disorder with a higher
      risk to develop coronary heart disease (CHD). In the heterozygous patients there
      are, however, variability in the atherosclerosis age of onset and severity. In
      recent years, it has been reported elevated levels of Lp(a) in FH, and it is
      proposed that this lipoprotein contributes to the development of CHD in these
      patients. This study evaluates the relationship between Lp(a) levels and the
      presence of CHD in FH. We included 38 patients with heterozygous FH with or
      without CHD (13 and 25 respectively), and a control group. In comparison to the
      control group, FH patients had significant elevated levels of Lp(a) (median 8.1
      vs 16 mg/dL), and a greater prevalence of hyper Lp(a) (with a cut-off level of 30
      mg/dL) (11.4 vs 25.7%). FH patients with CHD had higher levels of Lp(a) than
      those without CHD (22.8 vs 14.4 mg/dL). A significative negative correlation
      between age of onset of CHD and Lp(a) levels was found in females. CHD in FH was
      associated with male gender, older age, higher prevalence of hypertension, higher
      waist/hip ratios, higher levels of triglycerides and prevalence of
      hypertriglyceridemia. Our findings suggest that Lp(a) may play a role as an
      additional risk factor to develop atherosclerosis in FH.

PMID- 7726692
TI  - [Traumatic rupture of the aorta. A report of a case operated on with success].
AB  - The purpose of this paper is to present the case of a patient with traumatic
      rupture of the aorta, that was diagnosed and treated successfully. We describe
      the clinical data and diagnostic procedures of this case and we analyze the
      diagnostic and treatment aspects in accordance to the review of the literature.
      If, as in this case, the lesion does not extend through the adventitia and the
      entity is suspected based on the mechanism of the traumatism, a successful
      surgical treatment is feasible. This can be done by only clamping the aorta and
      doing the repair without an atrium to aorta by-pass, as was done in this case
      with no complications, or with the use of such a by-pass with a centrifugal pump
      with which it might be possible to prevent, in some cases, the paraplegia that
      can be associated with the clamping of the aorta. We conclude that a high degree
      of suspicion and a precise surgical technique are mandatory for a successful
      treatment of a traumatic rupture of the aorta.

PMID- 7726693
TI  - [Systemic arterial hypertension in pediatrics].

PMID- 7726694
TI  - [The usefulness of multiplanar transesophageal echocardiography].

PMID- 7726695
TI  - [The roots of medical ethics].

PMID- 7726696
TI  - Should a family history be taken from every woman with ovarian cancer.

PMID- 7726697
TI  - Practical approaches to a major educational challenge. Training students in the
      ambulatory setting.
AB  - Medical schools and residency training programs are recognizing the need to
      expand education in ambulatory medicine. Inpatients wards increasingly provide
      treatment for only the most critically ill patients and are required only for
      very specialized procedure-oriented technology. Most diagnostic and management
      decisions are being made in outpatient settings. This shift in where medical care
      occurs has led to a reassessment of the educational value of training students
      and house staff primarily on hospital-based wards. New training initiatives in
      ambulatory medicine are being developed in medicine, pediatrics, and family
      medicine, and the principal sites for most of this training are primary care
      offices, clinics, and health maintenance organizations. Program planners and
      individual preceptors are confronting numerous obstacles in their efforts to find
      effective solutions to the dilemmas raised by the need to train large numbers of
      students in these settings. This article will explore many of these obstacles,
      including the unique learning requirements of third-year students, the elements
      of a quality clinical training environment, and the precepting skills needed for
      this educational task. Finally, we propose for debate a model for ambulatory
      medical education that focuses on strengthening the ties between academia and the
      numerous training sites. By taking optimal advantage of academic and community
      attributes, we are more likely to be assured quality medical education, skilled
      teaching, and rigorous scholarship in ambulatory medicine.

PMID- 7726698
TI  - The impact of family history on ovarian cancer risk. The Utah Population
      Database.
AB  - OBJECTIVE: To estimate the relative risks and population attributable risks of
      ovarian cancer associated with family histories of cancer at several sites.
      METHODS: A matched case-control analytic study (662 cases, 2647 controls),
      employing the Utah Population Database, a genealogy of approximately 1 million
      individuals linked to cancer incidence data from the Utah Cancer Registry. Family
      history was assessed using kinship order and a kinship-weighted familial
      standardized incidence ratio statistic. RESULTS: Family histories of ovarian,
      uterine, breast, and pancreatic cancer were significantly associated with
      increased risk of ovarian cancer. The relative risk of ovarian cancer was 4.31
      (95% confidence interval [CI], 2.35 to 7.90) for women with a first-degree
      relative with ovarian cancer, 2.12 (95% CI, 1.19 to 3.78) for women with an
      affected second-degree relative, and 1.48 (95% CI, 0.98 to 2.24) for women with
      an affected third-degree relative. The odds ratio (OR) was 2.06 (95% CI, 1.44 to
      2.93) for those with the highest familial standardized incidence ratio. No age
      differences were observed between cases with and without a family history of
      ovarian cancer. There was substantial heterogeneity of family history effects by
      cell type. Increased parity was not protective among women with a strong family
      history of cancer at the sites studied (OR, 1.11; 95% CI, 0.38 to 3.26), although
      it was protective among women without a family history of these cancers (OR,
      0.29; 95% CI, 0.11 to 0.62). CONCLUSIONS: The risk of ovarian cancer was
      substantially increased among women with family histories of ovarian, uterine,
      pancreatic, and, to a lesser degree, breast cancer. Among women with family
      histories of any of these cancers, the risk of ovarian cancer is not diminished
      by high parity.

PMID- 7726699
TI  - Antiarrhythmic prophylaxis vs warfarin anticoagulation to prevent thromboembolic
      events among patients with atrial fibrillation. A decision analysis.
AB  - BACKGROUND: Patients with atrial fibrillation compared with those with sinus
      rhythm are at increased risk for thromboembolism, often mandating therapy
      directed at thromboembolism prevention. However, the safest, most efficacious
      strategy to prevent thromboembolism associated with atrial fibrillation is
      unknown. We developed a decision analysis to compare the risks and benefits of
      two common clinical strategies to prevent thromboembolism in the patient with
      atrial fibrillation: (1) sinus rhythm maintenance with quinidine sulfate or with
      amiodarone hydrochloride after cardioversion and (2) long-term anticoagulation
      with warfarin sodium. METHODS: A search was conducted of the English-language
      MEDLINE databases of the National Library of Medicine dated 1966 through December
      1992. The search was conducted by intersecting "quinidine," "warfarin," or
      "amiodarone" with "atrial fibrillation." Six of 249 articles concerning quinidine
      and five of 20 articles concerning warfarin were judged by multiple reviewers to
      meet predetermined inclusion and exclusion criteria. To our knowledge, no
      randomized, placebo-controlled trials of amiodarone therapy for atrial
      fibrillation have been published. Five of 112 identified articles concerning
      amiodarone involved nonrandomized trials that met the remaining selection
      criteria and were included in this analysis. RESULTS: Thromboembolic events and
      fatal nonthromboembolic adverse events during the course of therapy (defined as
      fatal proarrhythmia, fatal hemorrhage, and fatal noncardiac toxic effects) were
      considered to have equivalent weight. The total risk during therapy, defined as
      thromboembolic and fatal nonthromboembolic adverse events during the course of
      therapy, was evaluated over a range of baseline thromboembolism risks, from 1% to
      20% per patient-year. Quinidine therapy compared with no therapy was associated
      with increased total risk, unless baseline thromboembolism risk exceeded 11% per
      patient-year. Total risk during warfarin therapy was less than total risk during
      quinidine therapy for the entire range of baseline thromboembolism risks, from 1%
      to 20% per patient-year. Total risk during warfarin or amiodarone therapy was
      similar and less than that with no therapy for the entire range of baseline
      risks. CONCLUSIONS: Based on data from randomized, controlled trials of quinidine
      and warfarin, warfarin therapy appears to be the safest strategy for
      thromboembolism prevention in the patient with atrial fibrillation. The role of
      low-dose amiodarone therapy appears promising and warrants further study in
      randomized, controlled trials.

PMID- 7726700
TI  - Costs of duodenal ulcer therapy with antibiotics.
AB  - BACKGROUND: Intermittent or maintenance therapy with histamine2 antagonists,
      highly selective vagotomy, or antibiotic therapy to eradicate Helicobacter pylori
      all represent distinct, viable options to manage duodenal ulcer disease.
      Comparing the costs associated with these four approaches could help in deciding
      among them. METHODS: The decision model of a Markov chain was used to compare the
      costs of the four approaches and their influence on the natural course of
      duodenal ulcers. Direct costs were calculated from the average wholesale prices
      of drugs and from charges for medical services submitted to and allowed by the
      Health Care Financing Administration. Average annual income was used to estimate
      indirect costs. RESULTS: The model predicted that after antibiotic therapy, 99.7%
      of patient time is spent free of duodenal ulcer. The corresponding percentages
      were 96.6% for maintenance therapy, 94.4% for vagotomy, 89.4% for intermittent
      therapy, and 82.8% without therapy. For an individual patient after 15 years, the
      expected total costs of a treatment approach involving antibiotics are $995,
      compared with $10,350 for intermittent therapy with histamine2 antagonists,
      $11,186 for maintenance therapy with histamine2 antagonists, and $17,661 after
      vagotomy. Incorporating upper gastrointestinal tract endoscopy to verify
      eradication of H pylori raises the costs of the antibiotic therapy option to
      $2426. Increasing the annual infection rate of H pylori from baseline 1% to 10%
      raises the expected costs after 15 years to $3431. Decreasing the H pylori
      eradication rate from baseline 80% to 50% raises the costs to $2679. CONCLUSIONS:
      Compared with other options, antibiotics to eradicate H pylori are the cheapest
      therapy for duodenal ulcer and provide the least time spent with an active ulcer.
      From an economic perspective, antibiotics represent the treatment of choice.

PMID- 7726701
TI  - Prevalence, predisposing factors, and prognostic importance of postural
      hypotension.
AB  - OBJECTIVES: To determine the prevalence and predisposing factors of postural
      hypotension and to evaluate the effect of postural hypotension on 10-year
      vascular mortality in an elderly population. METHODS: A random sample of 480
      subjects aged 65 years or older was obtained in 1982. The participation rate of
      the subjects in the study was 72%, for a total of 347 subjects. Orthostatic
      testing and continuous ambulatory electrocardiographic recording, as well as
      comprehensive clinical evaluation, including medical history, physical
      examination, standard electrocardiography, chest radiography, blood pressure
      measurement, routine biochemical analysis, and determination of body mass index,
      were performed. In 1992, the 10-year mortality of subjects and causes of death
      were recorded from the mortality statistics. Of the participants, 184 (53%) had
      died and 163 were still alive. To determine the effect of postural hypotension on
      the 10-year mortality, the subjects who were alive and those who had died of
      vascular or nonvascular causes were compared. All of the examinations had been
      completed in 156 subjects who were still alive, in 109 subjects who had since
      died of vascular causes, and in 64 subjects who had died of nonvascular causes.
      RESULTS: An abnormal postural systolic blood pressure drop (-20 mm Hg or less)
      after standing for 3 minutes was demonstrated in 28.0% of subjects. There were no
      sex or age differences between the subjects with and without postural
      hypotension. No predisposing factors for postural hypotension other than elevated
      blood pressure were found. Chronic cardiovascular diseases, disability, body mass
      index, medication, and abnormal findings in ambulatory electrocardiographic
      monitoring were not associated with postural hypotension. In the univariate
      analysis, the extent of systolic or mean blood pressure change predicted neither
      vascular nor nonvascular death during the 10-year follow-up. On the other hand,
      diastolic blood pressure drop, in particular after standing for 1 minute, was
      associated with increased vascular mortality (odds ratio, 2.7; 95% confidence
      interval, 1.3 to 5.6). In the multivariate analysis, however, this association
      disappeared. CONCLUSIONS: Postural hypotension was common in an unselected
      elderly population. No predisposing factors for postural hypotension other than
      elevated blood pressure were found. The 10-year follow-up showed that postural
      diastolic, but not systolic, blood pressure drop predicted excess vascular
      mortality. However, this association disappeared in the multivariate analysis,
      thus being related to background factors such as cardiovascular diseases.

PMID- 7726702
TI  - Bystander cardiopulmonary resuscitation. Concerns about mouth-to-mouth contact.
AB  - BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) is performed on only a
      small percentage of patients who suffer cardiac arrest. We conducted a study to
      elucidate attitudes toward and potential obstacles to performance of bystander
      CPR. METHODS: Attitude survey of 975 people on the University Heart Center,
      University of Arizona, Tucson, mailing list. Participants were asked about their
      willingness to perform CPR under four conditions, with varying relationships
      (stranger vs relative or friend) and CPR techniques (chest compressions plus
      mouth-to-mouth ventilation [CC+V] vs chest compressions alone [CC]). RESULTS:
      Participants rated willingness to perform CPR and concern about disease
      transmission. Both relationship and CPR technique affected willingness to
      respond. Only 15% would "definitely" provide CC+V with strangers compared with
      68% who would "definitely" perform CC. Even with relatives or friends, only 74%
      would "definitely" provide CC+V compared with 88% who would "definitely" provide
      CC. Eighty-two percent of participants were at least "moderately" concerned about
      disease transmission. CONCLUSION: Concerns regarding mouth-to-mouth ventilation
      appear to create substantial barriers to performance of bystander CPR.
      Intensified educational efforts and investigations of new approaches to bystander
      CPR are warranted.

PMID- 7726703
TI  - Postprandial hypotension in elderly patients with unexplained syncope.
AB  - BACKGROUND: Syncope in older patients may be caused by a variety of disorders,
      including hypotension, but frequently remains unexplained. Postprandial
      hypotension is a common disorder of blood pressure regulation in the elderly.
      OBJECTIVE: To determine the pathogenic mechanisms and potential role of
      postprandial hypotension in elderly patients with otherwise unexplained syncope.
      METHODS: We studied 16 elderly patients with unexplained syncope and nine elderly
      controls. Blood pressure, heart rate, forearm vascular resistance, plasma
      norepinephrine level, and cardiac and splanchnic blood volumes were measured
      before and after a 1680-kJ meal. RESULTS: Eight elderly patients with syncope had
      postprandial hypotension, with a decline in supine mean arterial blood pressure
      of 17 +/- 2 mm Hg after a meal (P < .001). The blood pressure remained unchanged
      after the meal in the other patients with syncope and the controls. In patients
      with postprandial hypotension, systemic vascular resistance fell after the meal,
      while it remained unchanged in the other groups. Heart rate and plasma
      norepinephrine level increased to a similar extent in all three groups. Forearm
      vascular resistance increased only in the control subjects. Splanchnic blood
      volume increased by 26% (P < .01) in patients with syncope who had postprandial
      hypotension and by 22% (P < .01) in control subjects. Splanchnic blood volume
      remained unchanged in the patients with syncope without postprandial hypotension.
      CONCLUSIONS: Postprandial hypotension may be an important causative factor in
      elderly patients with unexplained syncope. The evaluation of syncope in elderly
      patients should therefore include blood pressure measurements surrounding a meal.
      Elderly patients with syncope who have postprandial hypotension fail to maintain
      systemic vascular resistance, probably because of splanchnic blood pooling
      without a compensatory increase in peripheral vascular resistance.

PMID- 7726704
TI  - Risk factors for the development of hyponatremia in psychiatric inpatients.
AB  - BACKGROUND: When inpatients who are on psychiatry services develop hyponatremia,
      medical consultation is usually required for evaluation and management, thus
      halting or delaying psychiatric treatment. Risk factors for the development of
      hyponatremia in this population have not been studied. METHODS: A case-control
      study of psychiatric inpatients in a tertiary care facility was performed. Sixty
      four patients who had a serum sodium level of less than 130 mmol/L were
      identified; three control subjects were chosen from the inpatient psychiatry
      service for each case. Risk factors investigated included medications,
      psychiatric diagnoses, basic demographic variables, and medical comorbidities.
      RESULTS: Univariate and logistic regression analyses revealed that, in addition
      to diuretic use (adjusted odds ratio, 8.2; 95% confidence intervals, 2.2 to
      30.8), use of fluoxetine (adjusted odds ratio, 21.4; 95% confidence interval, 5.3
      to 86.9), tricyclic antidepressants (adjusted odds ratio, 4.9; 95% confidence
      interval, 1.6 to 15.2), and calcium antagonists (adjusted odds ratio, 4.0; 95%
      confidence interval, 1.1 to 14.2) were all associated with the development of
      hyponatremia. Important comorbidities included elevated creatinine levels,
      chronic obstructive pulmonary disease, hypertension, systolic blood pressure, and
      diabetes. Although age was significantly associated with hyponatremia in
      univariate analyses, it was not significant in multivariate analyses.
      CONCLUSIONS: Among psychiatric patients, hyponatremia is often associated with
      factors other than psychogenic polydipsia, including medications and medical
      comorbidities. Although elderly psychiatric inpatients seem to develop
      hyponatremia more often than younger patients, once drugs and comorbidities are
      taken into account, age does not appear to be a significant risk factor for
      hyponatremia in this population.

PMID- 7726705
TI  - Zidovudine compared with didanosine in patients with advanced HIV type 1
      infection and little or no previous experience with zidovudine. AIDS Clinical
      Trials Group.
AB  - BACKGROUND: We conducted a trial to compare treatment with zidovudine or
      didanosine in patients with advanced human immunodeficiency virus type 1 (HIV-1)
      infection who had received little or no previous therapy with zidovudine.
      METHODS: Six hundred seventeen patients with acquired immunodeficiency syndrome
      (AIDS), advanced AIDS-related complex (CD4 cell count, < or = 0.30 x 10(9)/L
      [300/microL]), or asymptomatic HIV (CD4 cell count, < or = 0.20 x 10(9)/L)
      received zidovudine, 500 mg/d of didanosine, or 750 mg/d of didanosine in a
      randomized, double-blind allocation, with cross-over to alternative medication
      after development of an end point or serious toxic effect. To be eligible,
      patients must have received either no or up to 16 weeks of zidovudine therapy
      before entry into the study. Primary end points were development of a new AIDS
      defining event or death. Secondary clinical end points were new or recurrent AIDS
      defining events, or death, and survival. RESULTS: In the study as a whole, there
      were no differences in the relative risks (RRs) of the development of end points
      between treatment groups. However, there was a strong interaction between the
      relative efficacies of zidovudine and didanosine and previous experience with
      zidovudine. Among 380 patients with no previous zidovudine therapy, zidovudine
      was more effective than 750 mg/d of didanosine (RR, 1.43; 90% confidence interval
      [CI], 1.02 to 2.00), with a similar trend for zidovudine compared with 500 mg/d
      of didanosine (RR, 1.21; 90% CI, 0.86 to 1.71). However, among 118 patients with
      more than 8 weeks but no more than 16 weeks of previous zidovudine therapy, 500
      mg/d of didanosine was more effective than zidovudine (RR, 0.48; 90% CI, 0.27 to
      0.86); there was a similar trend for increased effectiveness of 750 mg/d of
      didanosine compared with zidovudine (RR, 0.61; 90% CI, 0.36 to 1.03). Among 119
      patients who had some but no more than 8 weeks of previous zidovudine therapy,
      there were no significant differences among the treatment arms. Similar findings
      were noted in the analysis of the two secondary clinical end points. No
      significant differences were found in efficacy between the groups receiving 500
      and 750 mg/d of didanosine. The major toxic effect associated with zidovudine was
      hematopoietic (granulocytopenia) and that associated with didanosine was
      pancreatitis (dosage, 750 mg/d). CONCLUSIONS: In patients with advanced HIV
      disease, zidovudine appears to be more effective than didanosine as initial
      therapy; however, some patients with advanced HIV disease may benefit from a
      change to didanosine therapy after as little as 8 to 16 weeks of therapy with
      zidovudine.

PMID- 7726706
TI  - Intestinal endometriosis masquerading as common digestive disorders.
AB  - Intestinal endometriosis mimics a wide variety of inflammatory, infectious, or
      neoplastic digestive diseases. To alert clinicians to its diverse manifestations,
      we describe nine patients who required laparotomy. The underlying diagnosis was
      elusive initially. In no case were symptoms clearly cyclic or temporally related
      to phases of the menstrual cycle. Presenting complaints included acute or
      subacute lower abdominal pain (three patients), hematochezia (two patients),
      signs or symptoms of small-bowel obstruction (two patients), peritonitis (one
      patient), and a partially obstructing sigmoid lesion (one patient). The findings
      of barium enema were nondiagnostic in the five cases in which it was performed.
      Surgery was needed in each case; indications included inability to exclude
      carcinoma (two patients), small-bowel obstruction (two patients), diffuse
      peritonitis (one patient), persistent colonic obstruction (one patient),
      pericolonic abscess (one patient), and intractable pain (one patient). Intestinal
      endometriosis has a diverse clinical spectrum, with nonspecific features in many
      patients. This disease should be considered during the evaluation of unexplained
      digestive complaints in women of childbearing years.

PMID- 7726707
TI  - Lowering high plasma cholesterol levels is not dangerous.

PMID- 7726708
TI  - Euthanasia.

PMID- 7726709
TI  - More on preconceptional counseling and intervention.

PMID- 7726711
TI  - The significance of glutathione peroxidase on myocardial protection in the rat
      hearts: the key of clarify the cause of vulnerability to reperfusion injury in
      infantile cardiac operations.
AB  - Selenium (Se) is an integral component of glutathione poeroxidase (GSHPx), and
      the serum selenium concentration is age-depend. We speculated that myocardial
      GSHPx had relation to reperfusion injury in open heart operations, especially in
      infants in whom GSHPx activity is low. This study correlated GSHPx activity with
      the serum and myocardial selenium concentrations in Wistar rats, which were
      divided into three groups, infants, Se-deficient rats, and control rats. Serum
      GSHPx activity in infant and Se-deficient rats (22.7 +/- 3.5 U/g protein, 24.6 +/
      22.2 U/g protein) was lower than that in controls (179 +/- 12.0 U/g protein).
      The serum selenium concentration in infant and Se-deficient rats (3.81 +/- 0.81
      micrograms/g protein, 2.06 +/- 1.69 micrograms/g protein) was also lower than
      that in controls (7.32 +/- 2.96 micrograms/g protein). The myocardial GSHPx
      activity was significantly lower in infants and Se-deficient rats (4.76 +/- 1.05
      x 10(-1) U/mg protein, 3.38 +/- 0.32 x 10(-1) U/mg protein) than that in controls
      (8.03 +/- 0.57 x 10(-1) U/mg protein). However, the myocardial selenium
      concentration in infants (1.42 +/- 0.24 x 10(-1) micrograms/mg protein) was
      significantly higher than that in the other groups (0.31 +/- 0.06 x 10(-1)
      micrograms/mg protein, 0.28 +/- 0.04 x 10(-1) micrograms/mg protein). Next, in Se
      deficient and control rats, isolated hearts were perfused for aerobically with
      Krebs-Henseleit solution in the Langendorff mode for 15 minutes, followed by 60
      minutes of global ischemia at 4 degrees C and then reperfused for 30 minutes in a
      working mode. The hemodynamic parameters were measured.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7726710
TI  - [Cancer immunology and preview to active specific cancer immunotherapy (vaccine
      therapy)].

PMID- 7726712
TI  - Cerebellar infarctions secondary to cranio-cervical anomalies: a case report.
AB  - We report a case of cerebellar infarctions which occurred in the territories of
      the bilateral posterior inferior cerebellar arteries. This case was complicated
      with cranio-cervical anomalies composed of assimilation of the atlas, atlanto
      axial dislocation, and basilar impression. The 40-year-old male patient had no
      detectable risk factors predisposing to atherosclerotic arterial occlusion or
      cardiogenic embolism, and there were no angiographic findings of atherosclerosis.
      It was, therefore, postulated that the cerebellar infarctions were secondary to
      those cranio-cervical anomalies. The developing mechanism is discussed.

PMID- 7726713
TI  - [Huge leiomyosarcoma of the mesentery: a case report].
AB  - A patient, a 63 year-old-man, was admitted suffering from discomfort in the left
      abdominal area; this proved to be a case of leiomyosarcoma of the mesentery. An
      upper gastrointestinal series revealed stenosis in the 3rd portion of the
      duodenum, and shift of the entire intestine to the right side. Computed
      tomography showed a giant mass lesion with a central necrosis. Selective arterial
      angiography showed a heterogeneous tumor stain with several feeders and drainage
      veins. A partial resection of the intestine around the Treitz's ligament and left
      hemicolectomy was required due to the tumor's invasion of the intestinal wall and
      transverse colon. The operation was successfully performed supported by the
      angiographic findings. The resected tumor was 23 cm in diameter, 2330 g in
      weight, and was filled with blood. The histological diagnosis was leiomyosarcoma
      of the mesentery. The patient has been doing well during the 6 months
      postoperative period.

PMID- 7726714
TI  - Symptoms of schizophrenia. Methods, meanings, and mechanisms.
AB  - BACKGROUND: The "group of schizophrenias," normally referred to with a single
      nominative, is phenomenologically heterogeneous. Its symptoms represent multiple
      psychological domains, including perception, inferential thinking, language,
      attention, social interaction, emotion expression, and volition. Studies of
      psychopathology have simplified this complex array in several ways, one of which
      is a subdivision into positive and negative symptoms. METHODS: This study
      examined the positive vs negative distinction in a sample of 243 patients with
      schizophrenia or schizophreniform disorder who were evaluated with the Scale for
      the Assessment of Negative Symptoms and the Scale for the Assessment of Positive
      Symptoms. A two-stage factor analysis was applied, beginning with a principal
      components analysis applying varimax rotation, followed by an extension analysis.
      The purpose of these analyses was to evaluate the correlational relationships of
      the various symptoms of schizophrenia. RESULTS: The results confirmed previous
      reports by our group and others suggesting that the symptoms of schizophrenia
      fall into three natural dimensions, as assessed by the correlational
      interrelationships: positive symptoms subdivide into psychotic and disorganized
      dimensions, while a third negative dimension also emerges. CONCLUSION: Because
      these dimensions have impressive consistency across studies, future work must
      examine their relationship to clinically relevant concepts such as prognosis or
      etiology and examine four different aspects: longitudinal course, neural
      mechanisms, relationship to treatment, and interrelationships in other
      pathological conditions.

PMID- 7726715
TI  - A longitudinal study of symptom dimensions in schizophrenia. Prediction and
      patterns of change.
AB  - BACKGROUND: Factor analytic studies have suggested that the symptoms of
      schizophrenia may be divided into three uncorrelated dimensions. This study
      examines the longitudinal course of the symptoms of schizophrenia using this
      three-dimensional perspective. METHODS: The sample was composed primarily of
      neuroleptic-naive patients suffering from schizophrenia. Subjects were studied in
      a prospective longitudinal design, with comprehensive structured assessments at
      index, discharge, and 6-month intervals after discharge over a 2-year period.
      RESULTS: Negative symptoms were already relatively prominent at the time of index
      evaluation; they tended to remain stable throughout the follow-up period. The two
      dimensions of positive symptoms, psychoticism and disorganization, although
      prominent at index evaluation, declined over the course of the follow-up period
      and tended to be less stable. A longitudinal factor analysis was conducted to
      determine whether the changes in symptoms followed any consistent pattern. We
      observed that all three groups of symptoms tended to change in unison and
      independently from one another. CONCLUSIONS: These results suggest that these
      three dimensions of psychopathology show different patterns of exacerbation and
      remission during the course of schizophrenia. This independent pattern of
      evolution suggests that these three dimensions should be studied further with
      respect to response to treatment, cognitive mechanisms, psychosocial correlates,
      and neural substrates.

PMID- 7726716
TI  - Signs and symptoms. What can they tell us about the clinical course and
      pathophysiologic processes of schizophrenia?

PMID- 7726717
TI  - A family study of manic-depressive (bipolar I) disease. Is it a distinct illness
      separable from primary unipolar depression?
AB  - OBJECTIVE: To determine whether bipolar I illness is autonomous or part of a
      multifactorial continuum with unipolar depression. In this study, we compare
      familial bipolar I illness and depression among three groups: probands with
      bipolar I disorder; probands with primary unipolar disorder; and controls. We
      also examine a continuum of severity between psychotic and nonpsychotic patients
      with bipolar I disorder. Considerable data suggest that bipolar I illness is
      distinct from unipolar illness as regards epidemiology, familial psychiatric
      illness, course, response to treatment, and biologic findings. METHOD: Probands
      were separated into bipolar I and primary unipolar depressive groups. Personally
      interviewed family members of these patients were compared on variables of
      bipolar illness or schizoaffective mania and unipolar or schizoaffective
      depression. A personally examined control group was compared with the relatives
      of the two proband groups. Similar analyses were performed using data obtained by
      a systematic family history method. For the same familial variables, psychotic
      and nonpsychotic manic probands were compared. RESULTS: Familial mania is more
      frequent in families of patients with bipolar disease than in controls or in
      families of patients with primary unipolar disorder. The latter two groups did
      not differ in amount of mania. Unipolar depressive illness or schizoaffective
      depression was higher in families of probands with bipolar and unipolar disorder
      than in controls. Probands with bipolar disease separated into those who had
      psychotic symptoms (including schizoaffective mania) and no psychotic symptoms
      did not differ from each other in risk for familial mania or depression.
      CONCLUSIONS: Bipolar I illness is a separate illness from primary unipolar
      illness because of an increase in familial mania. Patients with primary unipolar
      disease and controls show the same amount of familial mania. Lack of an increase
      in familial illness according to the severity of bipolar disease is against an
      affective continuum.

PMID- 7726718
TI  - The structure of the genetic and environmental risk factors for six major
      psychiatric disorders in women. Phobia, generalized anxiety disorder, panic
      disorder, bulimia, major depression, and alcoholism.
AB  - BACKGROUND: Although prior family and twin studies have examined the relationship
      between the genetic and environmental risk factors for pairs of psychiatric
      disorders, the interrelationship between these classes of risk factors for a
      broad range of psychiatric disorders remains largely unknown. METHODS: An
      epidemiologic sample of 1030 female-female twin pairs with known zygosity,
      ascertained from the Virginia Twin Registry, were evaluated by a personal
      interview conducted by mental health professionals, assessing lifetime history of
      phobia, generalized anxiety disorder, panic disorder, bulimia nervosa, major
      depression, and alcoholism. RESULTS: A multivariate twin analysis suggested the
      following. First, genetic, familial-environmental, and individual-specific
      environmental risk factors each cause a unique pattern of comorbidity among the
      six disorders. Second, genetic influences on these disorders are best explained
      by two factors, the first of which loads heavily on phobia, panic disorder, and
      bulimia nervosa and the second, on major depression and generalized anxiety
      disorder. Third, unlike other disorders, genetic influences on alcoholism are
      largely disorder specific. Fourth, familial-environmental influences on these
      disorders are best explained by a single factor that substantially influenced
      liability to bulimia nervosa only. Fifth, individual-specific environmental
      influences on the risk for these psychiatric disorders are best explained by a
      single factor, with highest loadings on generalized anxiety disorder and major
      depression and with large-disorder-specific loadings, especially on phobias,
      panic disorder, and alcoholism. CONCLUSIONS: These results support the following
      hypotheses: First, each major risk factor domain (genes, family environment, and
      individual-specific environment) influences comorbidity between these disorders
      in a distinct manner. Second, genetic influences on these six disorders are
      neither highly specific nor highly nonspecific. Neither a model that contains a
      discrete set of genetic factors for each disorder nor a model in which all six
      disorders results from a single set of genes is well supported. Third, the
      anxiety disorders are not, from a genetic perspective, etiologically homogeneous.
      Fourth, most of the genetic factors that influence vulnerability to alcoholism in
      women do not alter the risk for development of other common psychiatric
      disorders. These results should be interpreted in the context of both the
      strengths and limitations of multivariate twin analysis.

PMID- 7726719
TI  - Cingulotomy for intractable obsessive-compulsive disorder. Prospective long-term
      follow-up of 18 patients.
AB  - BACKGROUND: The purpose of this study was to assess prospectively long-term
      change in obsessive-compulsive disorder (OCD) symptoms in patients with an OCD
      diagnosis that was confirmed by structured interview and with documented
      unsuccessful trials of multiple medications and attempts at behavior therapy.
      METHODS: We conducted an unblinded preoperative and follow-up assessment of
      comorbid diagnosis; OCD, depressive, and anxiety symptoms; and functional status
      in 18 patients who underwent cingulotomy. RESULTS: At a mean follow-up of 26.8
      months, five patients (28%) met conservative criteria for treatment responders,
      and three others (17%) were partial responders. The group improved significantly
      in mean functional status, and few serious adverse events were found. Improvement
      in OCD symptoms was strongly correlated with improvement in depressive and
      anxiety symptoms. CONCLUSIONS: The rate of clinical improvement was consistent
      with a previous retrospective study in the same setting, indicating that 25% to
      30% of the patients who previously were unresponsive to medication and behavioral
      treatments are significantly improved after cingulotomy. Cingulotomy remains a
      last resort treatment for severely incapacitated patients who have not responded
      to all other state-of-the-art pharmacological and behavioral treatments for OCD
      and is not to be taken lightly.

PMID- 7726720
TI  - Reduced caudate nucleus volume in obsessive-compulsive disorder.
AB  - BACKGROUND: Current hypotheses about the neuroanatomical structures involved in
      obsessive-compulsive disorder (OCD) suggest abnormalities in cortical-striatal
      thalamic-cortical circuits. This study examined selected brain regions within or
      adjacent to these circuits. METHODS: Magnetic resonance imaging scans from 26
      patients with OCD and 26 healthy controls were analyzed to determine the volumes
      of the following structures: prefrontal cortex (cortex anterior to the genu of
      the corpus callosum), caudate nucleus, lateral and third ventricles, and whole
      brain. RESULTS: Patients with OCD had significantly smaller caudate nucleus
      volumes than controls (F[1,48] = 9.4, P = .004) but did not differ in prefrontal
      cortex size or in volumes of the lateral or third ventricles. Structural volumes
      were not significantly correlated with the duration or severity of OCD symptoms.
      CONCLUSION: Our findings provide additional evidence for pathological involvement
      of the caudate in OCD.

PMID- 7726722
TI  - Practical topics in neuropathology. College of American Pathologists
      Neuropathology Committee.

PMID- 7726721
TI  - An in vivo study of the prefrontal cortex of schizophrenic patients at different
      stages of illness via phosphorus magnetic resonance spectroscopy.
AB  - BACKGROUND: In this study, phospholipid metabolism of cell membranes, high-energy
      phosphate metabolism, and intracellular free magnesium concentration in the
      prefrontal cortex of first-episode drug-naive schizophrenic patients and
      medicated schizophrenic patients at different stages of illness were compared
      with those of controls. METHODS: Localized in vivo phosphorus 31 magnetic
      resonance spectra of the left dorsolateral prefrontal cortex of 11 drug-native,
      eight newly diagnosed medicated, and 10 chronic medicated patients with
      schizophrenia were compared with controls of similar gender, education, parental
      education, and handedness. RESULTS: Significantly decreased levels of
      phosphomonoesters in drug-native, newly diagnosed medicated, and chronic
      medicated patients and significantly increased levels of phosphodiesters in drug
      native patients were observed when compared with controls. There were no
      significant differences in the levels of high-energy phosphate metabolites
      between the groups except for a significant decrease in the inorganic
      orthophosphate levels of newly diagnosed medicated patients. A significant
      increase in the intracellular free magnesium concentration was observed in drug
      naive, newly diagnosed medicated, and chronic medicated patients compared with
      controls. There were no correlations between the patients' negative and positive
      symptoms and the observed phosphorus-containing metabolites. CONCLUSIONS: A
      reduction in precursors of membrane phospholipid are observed during the early
      and chronic stages of the schizophrenia illness, and breakdown products of
      membrane phospholipids are increased at the early stage of illness before
      medication treatment.

PMID- 7726724
TI  - Proficiency test performance and experience with College of American
      Pathologists' programs.
AB  - We examined rates of unacceptable results in a large interlaboratory proficiency
      test program, which is designed for small hospitals, clinics, and physician
      offices. The objective was to see whether rates of unacceptable results decrease
      as laboratories gain experience in interlaboratory comparison programs. We
      examined data from the College of American Pathologists' Excel Surveys, 1987
      through 1993, in the areas of chemistry, hematology, immunology, and blood bank.
      The data for laboratories with consistent participation show consistent and
      statistically significant improvement in performance for the first 3 to 4 years
      of proficiency testing. The data for all participants also suggest that
      laboratories with more experience with proficiency testing have lower rates of
      unacceptable results, and that these rates tend to decrease with each year of
      experience. These conclusions support the findings of other researchers who have
      documented the benefits of interlaboratory comparison programs and proficiency
      testing.

PMID- 7726723
TI  - Muscle biopsy.
AB  - OBJECTIVE: To provide practical guidelines for handling muscle biopsies to be
      submitted for outside processing and consultation. DESIGN: Review each step of
      handling a muscle biopsy and provide alternative means of tissue processing when
      feasible. RESULTS: Practical guidelines are presented for specimen selection,
      performance of needle biopsy, preparation of tissue for electron microscopy,
      preparation of tissue for shipping, clinical information to be provided, and
      submission of tissue for molecular and biochemical studies. CONCLUSIONS: Muscle
      biopsy samples to be sent to referral centers can be properly handled to avoid
      the problems noted by the Neuropathology Needs Assessment of the College of
      American Pathologists.

PMID- 7726725
TI  - The stability of survey-assigned assay values when surveyed control materials are
      used in a daily interlaboratory quality control program. The College of American
      Pathologists Chemistry Survey--Quality Assurance Service shared pool experience.
AB  - Two pools of lyophilized human control serum, distributed as challenges for the
      1990 and 1991 College of American Pathologists Comprehensive Chemistry Surveys
      were employed consecutively as two-level, daily, quality control materials in
      College of American Pathologists Quality Assurance Service Regional Quality
      Control programs. Because the Chemistry Survey and Quality Assurance Service use
      identical method codes and the materials are essentially stable, the variation of
      differences among Chemistry Survey and Regional Quality Control assay values is a
      sensitive measure of both the variation of accuracy among calibrator-assigned
      values and of the matrix response among calibrator/reagent lots following the
      time of initial Chemistry Survey assay. In the two cycles of data comparison, the
      Regional Quality Control means for the assay values of 15 stable routine
      chemistry analytes showed no statistically significant differences from the
      initial Chemistry Survey for 295 of 361 analyte-method combinations studied 16
      months later. Statistically significant changes between Chemistry Survey assay
      values and Regional Quality Control means most often occurred with closed rather
      than with open analytic systems and were predominantly in the same direction at
      both concentration levels. The magnitude of bias difference was usually less than
      the average within-laboratory standard deviation for the same analyte
      concentration. Of 64 analyte-pool combinations studied, a single instance of
      probable analyte instability was noted, ie, decreasing level I glucose during the
      first cycle. Our findings strongly support the usefulness of Chemistry Survey
      assigned target values to help strengthen the intralaboratory accuracy base. They
      also point out the need for and the utility of Regional Quality Control
      recalculated interlaboratory means to supplement assay values assigned at the
      time a control pool was put into use.

PMID- 7726726
TI  - Primary angiitis and angiopathy of the central nervous system and their
      relationship to systemic giant cell arteritis.
AB  - Three cases of primary angiitis of the central nervous system were compared with
      previously published cases. Most cases occurred in older adults, were diagnosed
      histologically, and had a male-female ratio of 2:1. Angiographically identified
      cases, demonstrating angiopathy but not necessarily vasculitis as might be seen
      in histologically identified cases, were found in younger adults and showed a
      male-female ratio of 1:2. The autopsy cases had some similarities to systemic
      giant cell arteritis, including many cases with vasculitis in large branches of
      the circle of Willis and foci of systemic vasculitis. Vasculitides in arteries of
      different sizes may result from different responses to a variety of antigens or
      immune complexes rather than represent different disease processes. If causative
      immune mechanisms can be identified, primary angiitis of the central nervous
      system may become classified immunologically rather than histopathologically.

PMID- 7726727
TI  - Superiority of neural networks over discriminant functions for thalassemia minor
      screening of red blood cell microcytosis.
AB  - We compared the utility of screening red blood cell (RBC) microcytosis for
      thalassemia minor using backpropagation neural networks, linear and quadratic
      discriminant functions, and previously reported discriminant functions based on
      RBC indices. Screening classification of cases representing possible thalassemia
      minor (n = 60) and non-thalassemic microcytosis (n = 60) were studied. Among
      eight RBC indices evaluated, the RBC count was the best univariate discriminant
      function. Multivariate stepwise discriminant analysis selected the RBC count, the
      mean corpuscular volume, and the percentage of hypochromic cells as the most
      discriminatory subset of RBC indices. Optimized linear and quadratic discriminant
      functions based on these indices performed better than seven previously reported
      multivariate discriminant functions. However, optimized neural networks were
      superior to all other discriminant methods studied, averaging 94.1% discriminant
      efficiency, 94.2% sensitivity, and 94.2% specificity.

PMID- 7726728
TI  - Pathology of the gallbladder in gallstone pancreatitis.
AB  - Although cholecystectomy is routinely performed as a part of treatment for
      gallstone pancreatitis, detailed histopathologic features of the gallbladder have
      not been described. In this study, the pathologic findings of 53 gallbladders
      from patients with clinical and laboratory evidence of gallstone pancreatitis are
      described. The presence of intraepithelial neutrophilic aggregates, a histologic
      finding associated with common bile duct obstruction, was identified in 32
      (60.4%) cholecystectomy specimens and was the most common pathologic findings.
      Changes of acute cholecystitis and chronic cholecystitis were found in 15 (28.3%)
      and 6 (11.3%) gallbladders, respectively. Fat necrosis, which is
      characteristically associated with acute pancreatitis, was the most specific
      histologic change, but it was seen in the adventitia of only four gallbladders.
      The similarities of pathologic findings in gallstone pancreatitis and common bile
      duct obstruction emphasize the role of choledocholithiasis in the pathogenesis of
      pancreatitis associated with cholelithiasis.

PMID- 7726730
TI  - Intraosseous malignant peripheral nerve sheath tumor. Report of a case and review
      of the literature.
AB  - We report a case of a malignant peripheral nerve sheath tumor arising in the
      distal femur of a 28-year-old man who had no stigmata of von Recklinghausen's
      disease. Roentgenograms and computed tomographic scans of the distal femur showed
      a single lytic intraosseous lesion with minimal soft tissue extension. Light
      microscopy demonstrated a tumor composed of spindle cells with myxoid areas.
      There was some nuclear pleomorphism and mitotic activity. The tumor cells were
      immunoreactive for S100 protein and neuron-specific enolase. Ultrastructurally,
      there were cells with long processes, which were focally invested by basal
      lamina. Some cells had numerous micropinocytotic vesicles. The tumor recurred in
      the femur 15 months following the initial curettage. Computed tomographic scan of
      the lungs at that time showed a nodule, which has since enlarged. Primary osseous
      malignant peripheral nerve sheath tumors are uncommon. A literature review
      revealed only 18 previous cases, the majority of which occurred in the mandible
      or maxilla. This is a rare case of intraosseous malignant peripheral nerve sheath
      tumor of a long bone, with both immunohistochemical and ultrastructural
      confirmation of nerve sheath differentiation.

PMID- 7726729
TI  - A microwave method that enhances detection of aberrant p53 expression in formalin
      fixed, paraffin-embedded tissues.
AB  - OBJECTIVE: Detection of aberrantly accumulated p53 protein by
      immunohistochemistry may have prognostic significance in many human neoplasms. We
      wished to identify a technique applicable to formalin-fixed, paraffin-embedded
      sections that would reliably yield results equivalent to frozen-section
      immunohistochemistry. DESIGN: We compared the frequency of p53 immunostaining
      obtained by applying monoclonal antibodies PAb1801, DO7, or DO1, a 1:1 PAb1801
      DO7 cocktail, and a 1:1 PAb1801-DO1 cocktail to fresh-frozen and formalin-fixed,
      paraffin-embedded tissues from 36 lung and upper aerodigestive-tract carcinomas.
      With the formalin-fixed tissues, we compared pepsin predigestion with microwave
      irradiation in citrate buffer as means of enhancing the sensitivity of p53
      detection. SETTING AND PATIENTS: All tissues were obtained from surgical
      resections of tumors, from patients who underwent surgery at the Minneapolis
      Department of Veterans Affairs Medical Center between 1990 and 1992. MAIN OUTCOME
      MEASURES: The sensitivity of different paraffin section techniques for
      immunohistochemical detection of accumulated p53 protein was determined in
      reference to the optimal frozen section method (defined as the method that
      yielded the greatest number of p53-positive cases in frozen tissue). RESULTS:
      Microwave antigen retrieval markedly enhanced staining with PAb1801 and DO7 in
      paraffin sections, as compared with pepsin predigestion and no pretreatment. This
      technique was 100% sensitive relative to the optimal frozen tissue method. In
      contrast, staining with DO1 alone was not enhanced by microwaving. CONCLUSIONS:
      Microwave pretreatment in conjunction with the use of either PAb1801 or DO7 is
      highly efficacious in the immunohistochemical detection of aberrant p53
      expression in formalin-fixed, paraffin-embedded tissues.

PMID- 7726731
TI  - Shadow cells in an intracranial dermoid cyst.
AB  - A case of an intracranial dermoid cyst containing shadow cells is presented. This
      case expands the group of lesions in which shadow cells, indicative of hair
      matrical differentiation, have been described.

PMID- 7726732
TI  - Malignant lymphoma presenting with an elevated serum CA-125 level.
AB  - An 80-year-old woman presented with fevers, night sweats, and weight loss. Her
      serum CA-125 level was markedly elevated (380 U/mL; normal < 35 U/ml). At post
      mortem examination, the patient had widespread intermediate-grade malignant
      lymphoma with extensive infiltration of the greater omentum and pelvic
      peritoneum. Immunohistochemistry for CA-125 documented intense staining in the
      reactive mesothelial cells of the peritoneum; the tumor cells were not
      immunoreactive. CA-125 is a glycoprotein recognized by a monoclonal antibody
      raised against an ovarian-cancer cell line. Elevated levels have been reported
      rarely in patients with malignant lymphoma, and the pathophysiology of this
      finding has not been understood. Our data support the hypothesis that elevated CA
      125 levels may reflect production by reactive mesothelium in patients with benign
      or malignant diseases involving the peritoneum, including malignant lymphoma. The
      clinical application of this marker, therefore, is broader than the recognized
      monitoring of patients with ovarian carcinoma.

PMID- 7726733
TI  - Proliferative glomerulonephritis with unusual, organized, cylindrical deposits
      associated with angioimmunoblastic lymphadenopathy-like T-cell lymphoma.
AB  - We describe an elderly man who developed angioimmunoblastic lymphadenopathy-like
      T-cell lymphoma, followed by acute renal failure 2 months later. Renal biopsy
      revealed proliferative glomerulonephritis, which was characterized by enlarged
      glomeruli with increased cellularity, thickened capillaries, intracapillary
      inflammatory cells, focal necrosis, and fibrin extravasation. Immunofluorescence
      studies revealed capillary and mesangial deposits of IgG, IgM, IgA, Ig kappa, Ig
      lambda, and C3. Electron microscopy revealed unusual, organized, electron-dense
      deposits in the capillary walls and mesangium. The deposits occurred as
      accumulations of large rigid tubules or cylinders, which, in longitudinal
      section, were double-walled. In transverse section, the deposits were annular or
      horseshoe shaped and occasionally had a central filament. The morphologic
      characteristics of these deposits are different from those seen in
      cryoglobulinemia or fibrillary and immunotactoid glomerulopathies. The
      significance of these deposits is uncertain; they may represent a cryoglobulin or
      an abnormal serum protein related to angioimmunoblastic lymphadenopathy-like T
      cell lymphoma. The findings in this case expand the morphologic spectrum of
      glomerular lesions that may be associated with malignant lymphoproliferative
      disorders and, particularly, angioimmunoblastic lymphadenopathy-like T-cell
      lymphoma.

PMID- 7726734
TI  - Peroxidase-catalysed oxidation of different dibenzazepine derivatives.
AB  - According to a recent hypothesis suggesting the potential role of free radical
      formation in the clozapine-induced agranulocytosis, we have evaluated the
      susceptibility to the peroxidase-mediated oxidation of different dibenzazepine
      analogues. On the one hand, compounds with an arylamine group such as clozapine
      or isoclozapine present a high reactivity in the horseradish peroxidase or
      myeloperoxidase systems and, on the other hand, fluperlapine, though known to
      induce agranulocytosis, and other dibenzothiazepine and dibenzoxazepine
      derivatives appear insensitive to oxidation. Consequently, among tricyclic
      derivatives, the way of diaryloxa- and diarylthiazepine compounds could be an
      alternative for the development of safer drugs such as antipsychotics.

PMID- 7726735
TI  - Synthesis of phthalimido-desmuramylpeptide analogues as potential
      immunomodulating agents.
AB  - The preparation of immunologically active phthalimido desmuramylpeptide analogues
      2e-h, 4c-d, and 7b is described. The N-acetylmuramic acid in the muramyl
      dipeptide has been replaced by a phthaloylated acyclic moiety such as N
      phthaloylated amino acids 1a-c, 2-(2-phthalimidoethoxy)acetic acid 3, or by the
      carbocyclic rac. trans-2-(2'-phthalimidocyclohexyloxy)acetic acid 6.

PMID- 7726736
TI  - Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XXVII.
      Inhibition of leucocyte adherence to endothelium by the oligoamine RE 1492C and
      the NO-donor RE 2047.
AB  - The oligoamine RE 1492C (N,N',N"-4-phenylbutyl-1,3,5-benzene-trimethanamine
      N,N',N"- triethylcarbamate ) inhibited the electrically provoked leucocyte
      adhesion to the endothelium of rat mesenteric venoles. An oral dose of 60 mg/kg
      gave a significant inhibition of 65-78%. This is comparable to effects seen after
      i.v. administration of iloprost or PGE1, respectively. In the same dosage the NO
      donor RE 2047 (3-methyl-N-nitroso-sydnone-5-imine) produced an inhibition of 21
      27%.

PMID- 7726737
TI  - Transdermal absorption of dimethindene in man.
AB  - Dimethindene and its metabolite N-demethyldimethindene were determined in human
      urine after dermal administration of dimethindene. The HPLC-method used was
      previously described. Data of 8 volunteers are presented. After 32 h an average
      of 0.023% of the administered dose of dimethindene and 0.022% of N
      demethyldimethindene were excreted into urine. Since also after oral
      administration of dimethindene only about 1% of unmetabolised dimethindene is
      found in urine it can be concluded that a certain amount of dimethindene is
      absorbed through the skin after dermal administration.

PMID- 7726738
TI  - Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XXVIII:
      Oligoamines with fluorescent properties. Part C: Fluorescent oligoamines with
      enhanced hydrophilic properties.
AB  - Fifteen fluorescent oligoamines with one or two fluorescent groups and two or
      three basic N-functions were prepared and tested for antiplatelet activity (Born
      test). Five compounds involving three different fluorophores, i.e. 2-fluorenyl, 1
      pyrenyl, and 9-phenanthryl, show an IC50 of 7-11 mumol/L. They are suitable to
      serve as probes in the field of oligoamine-biopolymere interactions.

PMID- 7726739
TI  - New NO-donors with antithrombotic and vasodilating activities, XII: Mesoionic
      oxatriazoles and related noncyclic nitrosohydrazine derivatives.
AB  - Mesoionic 1,2,3,4-oxatriazolimines and the corresponding oxatriazolones were
      prepared and tested for their antiplatelet and antithrombotic activities. In the
      Born-test 5-amino-3-phenyl-1,2,3,4-oxatriazolimine chloride inhibited the
      platelet aggregation halfmaximally in a concentration of 50 nmol/L. Its N
      ethoxycarbonyl derivative inhibited thrombus formation in arterioles of rats by
      48% (10 mg/kg, 2 h after p.o. administration). These effects appear to be related
      to the formation of intermediate nitrosohydrazine derivatives. This aspect was
      supported by the activities in noncyclic nitrosohydrazines (2 compds.),
      nitrosohydrazones (2) and nitrosohydrazides (11). Five of them exhibited an IC50
      < 100 nmol/L in the Born-test. In a thrombotic model strong inhibition of
      thrombus formation was observed after intravenous application. The 1-nitroso-1
      benzylhydrazine even exhibited strong inhibitory effects after oral
      administration.

PMID- 7726740
TI  - Structure-activity relationship studies of CNS agents, XIX: Quantitative analysis
      of the alkyl chain effects on the 5-HT1A and 5-HT2 receptor affinities of 4-alkyl
      1-arylpiperazines and their analogs.
AB  - The 5-HT1A and 5-HT2 receptor affinity of a set of 44 N-alkylated 1-aryl
      piperazines and their analogs has been analyzed: the n-hexyl derivatives were the
      most potent and the most selective 5-HT1A ligands of all the investigated N-alkyl
      homologues. The alkyl chain may stabilize the 5-HT1A receptor-ligand complex by
      hydrophobic forces. A set of the alkyl substituent contributions (CHT1A) for
      prediction of the 5-HT1A affinity of N-alkyl derivatives of 1-arylpiperazines and
      related compounds have been defined on the basis of the Free-Wilson analysis.

PMID- 7726741
TI  - [Synthesis and reactions of 2-methylene-canrenone].
AB  - Starting from the Mannich salt 1 of the aldosterone antagonist canrenone or from
      2-methylene-canrenone (2) the A-ring annulated hetero- and carbocycles 5, 6, 8-13
      were prepared. Receptor (estradiol, progesterone, androgen, gluco- and
      mineralocorticoid) binding studies and competition studies with the serum
      proteins SHBG and CBG were carried out using the compounds 2, 3, 4b, 5, 6b, 8 and
      12. The relative binding affinities with CBG are below 1%, in all other cases
      lower than 0.01%.

PMID- 7726742
TI  - [Heterocyclic annulated steroids from 2-hydroxymethylene-canrenone].
AB  - A-ring annulated heterocycles, the isoxazole 6, the pyrazoles 8 and the
      pyrimidines 9 are prepared starting from 2-hydroxymethylene canrenone 1. Binding
      studies were carried out with the compounds 1 and 6-8 using estrogen,
      progesterone, androgen, gluco- and mineralocorticoid receptors as well as the
      serum proteins SHBG and CBG: the substances were inactive on the receptor level.
      1, 7 and 8a show weak binding affinity to CBG.

PMID- 7726743
TI  - [Acetylation of spironolactone, canrenone and 2-methyl-canrenone].
AB  - Reaction of the title compounds with acetic anhydride and acetyl chloride yields
      the 3,5-dien-3-yl acetate 2, the isomeric 2,4,6- and 3,5,7-trien-3-yl acetates 3
      and 4 as well as the 2,4,6,8(14)-tetraen-3-yl acetate 7. The 2 alpha-methyl-8,14
      didehydro-canrenone (9) is obtained by hydrolysis of 7. Binding affinities of 7
      and 9 to hormone receptors as well as serum proteins (SHBG, CBG) are
      investigated. The compounds are inactive.

PMID- 7726744
TI  - Synthesis of some thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones as potential platelet
      aggregation inhibitors.
AB  - Twenty new compounds having 2-methyl-6-benzylidenethiazolo[3,2-b]- 1,2,4-triazole
      5(6H)-one (2a-d) and 2-methyl-6-(alpha-aminobenzyl)thiazolo-[3,2-b]-1,2,4-
      triazole-5-ol (5-20) structures were synthesized. Their structures were confirmed
      by elemental and spectroscopic analysis and their platelet aggregation inhibitory
      activities were investigated.

PMID- 7726745
TI  - [Structure-activity relations of isochromanylpenicillins].
AB  - Isochroman is substituted and bound to 6-aminopenicillanic acid either directly
      or by a spacer in 1-position. In addition to the isochromans two homoisochromans
      are tested. The activities of the new penicillins against grampositive and
      gramnegative bacteria are compared with those of benzylpenicillin.

PMID- 7726746
TI  - Some analogues of 1,4-disubstituted piperazines as hypnotic and sedative agents.
AB  - Preparation, analytical data, and biological properties such as acute toxicity,
      influence on spontaneous and amphetamine induced locomotor activity, hypnotic
      activity, influence on hexobarbital narcosis and anticonvulsant activity of new
      analogues of pyrimidyl piperazines--ethyl 3-[4-(2-pyrimidyl)-1-piperazinyl]-3
      oxopropanoate (4), 1-[4-(2-pyrimidyl)-1-piperazinyl]-1,3-butandione (5), ethyl 3
      [4-(2-pyrimidyl)-1-piperazinyl]butanoate (6) and 1-[4-(2-pyrimidyl)-1
      piperazinyl]-2-acetyl-1-hexanone (7)--are reported.

PMID- 7726747
TI  - Cytotoxicity and antimicrobial activity of some naphthol derivatives.
AB  - 2-Hydroxymethyl-1-naphthol diacetate (TAC) and sixteen Mannich base derivatives
      of naphthol were prepared and examined for cytotoxicity and antimicrobial
      activity. Cytotoxicity was examined against four human carcinoma cell lines.
      Several derivatives were effective at concentrations < 4 micrograms/ml. TAC
      showed the highest cytotoxicity. Inhibition of DNA-, RNA-, and protein synthesis
      by TAC was also studied and discussed. TAC also exhibits potent antimicrobial
      activity against Enterobacter clocae 23355, Klebsiella pneumonia 13883, Proteus
      vulgaris 13315, Pseudomonas aeruginosa 27853, Candida parapsilosis, Candida
      tropicalis, Trichosposon beigelli, and Rhodotorul spp. with minimum inhibitory
      concentrations of 0.1-0.4 microM. These results indicate that esterification by
      Bruson reaction of 1-naphthol Mannich base to TAC enhances the cytotoxicity and
      antimicrobial activity.

PMID- 7726750
TI  - [Effect of fog on diurnal changes in peak expiratory flow rates in an asthmatic].
AB  - To evaluate the effects of fog on asthmatics, we analyzed the symptoms of a 45
      year-old female during the foggy season and the relation between diurnal peak
      expiratory flow rate (PEFR) and fog and other meteorological factors. Her asthma
      attacks had been induced by specific smells: perfume, smoke from burning grass or
      industrial smoke. Two years previously, she had moved to the suburbs of Sapporo,
      where fog frequently occurs. From that time her asthmatic symptoms had been
      exacerbated, so it was suspected that the fog might have had some influence. We
      analyzed 251 measures of PEFR from June to August 1994. The average and standard
      deviation of PEFR in the absence of fog and specific smells was 403 +/- 40 L/min
      (n = 195). PEFR was significantly lower (p < 0.01) when it was foggy (347 +/- 60
      L/min; n = 40), when specific smells were present (333 +/- 60 L/min; n = 5) and
      when there were both fog and specific smells (340 +/- 53 L/min: n = 11). On the
      other hand, there were no changes associated with other meteorological factors:
      barometric pressures, relative humidity, mean temperature, minimal temperature
      and most frequent wind direction. These results suggested that the inhalation of
      fog decreases PEFR and is an exacerbating factor in bronchial asthma.

PMID- 7726748
TI  - [Effect of dexamethasone on intercellular adhesion molecule-1 expression on
      cultured bronchial epithelial cells stimulated by inflammatory cytokines].
AB  - Bronchial asthma is characterized as a chronic inflammation of the airway that
      causes an infiltration of lymphocytes and eosinophils. Cell to cell interaction
      or cell to tissue interaction is essential for infiltration of eosinophils to
      underlying tissues. These phenomena are closely related to the expression of
      intercellular adhesion molecule-1 (ICAM-1). Inhalation of steroids, such as
      beclomethasone dipropionate, is commonly used to cure airway inflammation. In
      this study, we investigated the effect of cytokines on ICAM-1 expression on human
      bronchial epithelial cell lines, NCI-H292. Moreover, the effect of dexamethasone
      on ICAM-1 expression stimulated by IL-1 beta, TNF-alpha and IFN-gamma was
      observed. Treatment with IL-1 beta, TNF-alpha and IFN-gamma dose-dependently
      increased ICAM-1 expression on NCI-H292 cells. Inhibitory effects were exerted by
      dexamethasone on ICAM-1 expression in cells stimulated by IL-1 beta and IFN-gamma
      in a dose-dependent manner, but not in cells stimulated by TNF-alpha. These
      results suggest that the inhibition of ICAM-1 expression could be related to the
      pharmacological action of steroid drugs.

PMID- 7726749
TI  - [The host defense--proposal of primitive T cell response (PT response)].

PMID- 7726751
TI  - [Investigation into the therapeutic efficacy of continuous isoproterenol
      inhalation in relation to respiratory infections in asthmatic children].
AB  - In our Department, continuous isoproterenol inhalation therapy has been conducted
      on status asthmatics over the last 10 years. In the present study, we
      investigated whether there are any differences in the therapeutic efficacy of
      continuous inhalation of isoproterenol in the presence or absence of respiratory
      infections which may induce or aggravate asthma attacks. The treatment period was
      significantly longer in patients with pneumonia. Further prolongation of the
      treatment period was noted in patients with atelectasis. However, there were no
      apparent differences in therapeutic efficacy according to age or the severity of
      attacks. These findings suggest that continuous inhalation of isoproterenol is
      very effective for status asthmatics if respiratory infections are thoroughly
      controlled.

PMID- 7726752
TI  - [IgE production and gene expression of interleukin-4 and interferon-gamma by
      peripheral mononuclear cells in asthmatic children].
AB  - In asthmatic children without he egg allergy, spontaneous IgE production of PBMC
      showed 1.27 +/- 0.28 IU/ml (Mean +/- SE) and IgE production of Dermatophagoides
      farinae (Df) stimulated PBMC after which IFN-gamma decreased to 0.89 +/- 0.23
      IU/ml (Mean +/- SE) (p < 0.001). IgE production of Ovalbumin (OVA) stimulated
      PBMC after which IFN-gamma showed no decrease. In asthmatic children with hen egg
      allergy, IgE production of OVA stimulated PBMC and IFN-gamma decreased to 1.0 +/-
      0.52 IU/ml (Mean +/- SE). In spontaneous IgE production it was 1.61 +/- 0.91
      IU/ml. (p < 0.05). IL-4 mRNA was expressed in spontaneous PBMC in asthmatic
      children, but not in healthy non atopic children. The expression of IL-4 mRNA was
      suppressed in Df stimulated PBMC followed by IFN-gamma in asthmatic children. In
      asthmatic children, IFN-gamma mRNA were expressed in Df stimulated PBMC after
      which IFN-gamma. And simultaneously IgE production in Df stimulated PBMC were
      suppressed by addition of IFN-gamma.

PMID- 7726753
TI  - [An epidemiological study of factors relating to mercury sensitization].
AB  - We investigated factors relating to mercury sensitization in 156 medical students
      (mean age 22.7 +/- 2.4, mean +/- S.D., male 113, female 43). Their allergic
      symptoms, lifestyles and family histories were studied by questionnaire. Patch
      tests were performed on them with HgCl2 (0.05%aq.), NiSO4 (5%aq.), PPD (2%pet.)
      and urushiol (0.01%pet.). Anti-dermatophagoides and anti-cryptomeria pollen IgE
      antibodies in serum were also measured. While the positive rates of urushiol,
      nickel and PPD were 11.1%, 5.1% and 2.6%, respectively, that of mercury was as
      high as 12.8%. Each allergen specific antibody positivity and past histories of
      allergic diseases were not associated with mercury sensitization (by the chi
      square test). Mercury sensitized students had significantly more frequently
      experienced eczema caused by cosmetics, shampoos, soaps and haircreams (by the
      chi-square test, p < 0.005). They also had significantly more teeth treated with
      metals compared to the controls (one-tailed t-test, p < 0.05). And their urinary
      mercury concentrations were significantly higher than those of the controls (one
      tailed t-test, p < 0.05). These findings suggest that mercury sensitization is
      associated with exposure to mercury in the living environment.

PMID- 7726754
TI  - [Clinical effect of Nd: YAG laser treatment on the allergic rhinitis].

PMID- 7726755
TI  - [A case of agranulocytosis which occurred several hours after the
      readministration of D-penicillamine accompanied by shivering-chillness].

PMID- 7726756
TI  - [Alcohol beverage advertisements--survey of weekly magazines].
AB  - This paper presents an analysis of alcohol beverage advertisements appearing in
      weekly magazines and comics. Few studies have be undertaken on this sector of the
      mass media in Japan. The results are compared with those of a similar study in
      the United States. We also review alcohol advertisements on television and the
      drinking scenes shown in comics. On the average, Japanese magazines tend to
      contain fewer alcohol advertisements than American magazines. However, 18 (53%)
      in 34 weekly magazines contained alcohol advertisements showing that such
      magazines are an important medium for alcoholic beverage advertising in Japan.
      There were also alcohol advertisements targeting to particular populations,
      youths and women, which may be connected with the increase in drinking in these
      groups. Alcohol advertisements in the mass media should be monitored continuously
      as public health issue.

PMID- 7726757
TI  - [Association between alcoholics and the genotypes of ALDH2, ADH2, ADH3 as well as
      P-4502E1].
AB  - We examined the genotypes of ALDH2, ADH2, ADH3 and P-4502E1 loci of alcoholics
      and nonalcoholics. Also we compared the frequencies of the homozygous ALDH2*1/1
      genotype and heterozygous ALDH2*1/2 genotypes in alcoholics. Our study reported
      differences in the allelic frequencies of ALDH2, ADH2 and ADH3 loci between
      alcoholics and nonalcoholics. For alcoholics, it was indicated that ADH2 and ADH3
      plays an important role for alcoholism. For genotypes of P-4502E1, no significant
      difference was observed between alcoholics and nonalcoholics. Alcoholics with the
      heterozygous ALDH2*1/2 genotype had significantly higher frequency of the ADH2*1
      than that of alcoholics with ALDH2*1/1 genotype. Concerning the alcoholics with
      the heterozygous ALDH2*1/2 genotype, we assumed that ADH2*1 plays a role for the
      development of alcoholism.

PMID- 7726758
TI  - Cost-benefit evaluation of artificial insemination for genetic improvement of
      wool-producing sheep.
AB  - The financial costs and benefits associated with the use of artificial
      insemination (AI) in commercial flocks are evaluated. Benefits are calculated in
      terms of net present values after summing the discounted value of benefits over
      20 years. Two breeding strategies are evaluated. With the first, AI is used to
      produce flock ewes and wethers. The method is unlikely to be profitable unless
      high breeding value rams are available for AI programs with fresh semen. With the
      second, AI is used to produce home-bred rams, which in turn sire flock ewes and
      wethers. This approach is more likely to be profitable. The cost of AI per lamb
      weaned from laparoscopic AI programs is about $100. Benefits exceed this cost for
      rams of very high merit when wool prices are moderate or higher. Flock structure
      has a significant effect on the benefits. Flocks with low wether retention rates
      have benefits half that of flocks that retain most wethers to 6 years of age. AI
      with purchased semen also provides benefits to risk management for owners of
      commercial flocks who wish to breed their own replacement flock rams.

PMID- 7726759
TI  - Intake of trichostrongylid larvae by goats and sheep grazing together.
AB  - Cashmere goats and Merino sheep were grazed together at 7.5 animals per ha on
      annual rye grass and clover pasture in southern Victoria, a winter rainfall area.
      Intake of parasitic larvae was measured in oesophageal extrusa samples collected
      from 2 animals of each species, 4 times in one week, on 7 occasions between mid
      March (autumn) and mid-June (winter). Pasture contamination with larvae was
      measured at the same times. The number of larvae per kg of green grass was lower
      than on green clover; the most heavily contaminated portion of the pasture was
      the mat of dead herbage on the ground. The diet selected by goats contained more
      green grass and dead herbage and less clover that that of sheep (P < 0.01). Goats
      ingested 643 infective trichostrongylid larvae per kg dry matter intake (DMI)
      versus 274 per kg DMI for sheep in autumn, increasing to 1892 versus 1143 in
      early winter. The heavier trichostrongylid burdens of goats compared with sheep,
      when grazed together, are due in part to greater rates of infection consequent on
      different grazing patterns as well as greater susceptibility to infection.

PMID- 7726760
TI  - Diarrhoea in merino ewes during winter: association with trichostrongylid larvae.
AB  - A study on 3 farms, each having a preventive strategy for the control of nematode
      infections, determined the risk factors associated with diarrhoea among Merino
      ewes in winter. Comparisons were made among groups of mated and unmated ewes with
      and without treatment with controlled-release capsules containing albendazole.
      Diarrhoea was assessed from the accumulations of faeces around the breech (dag
      score) and related to worm egg counts, total worm counts and histopathological
      findings. The overall prevalence of severe dag in ewes not treated with a capsule
      was 26% (221/844). In comparison, only 2.7% of treated ewes had severe dag. The
      adjusted odds ratio on each farm indicated that untreated ewes were between 12
      and 16 times more likely to be affected with severe dag than ewes treated with a
      capsule. The effect of lactation was significant on only one farm whereas initial
      body weight had no significant effect. There was no significant association
      between worm egg counts and the occurrence of severe dag. There were
      significantly more eosinophils in the small intestine of ewes affected with
      severe dag compared with unaffected ewes. There were no significant differences
      in mast cell and globule leucocyte numbers between affected and unaffected ewes.
      This study provides strong evidence that the main cause of diarrhoea among Merino
      ewes grazing winter and early spring pastures is the ingestion of
      trichostrongylid larvae even by sheep that have a well-developed protective
      immune response to these parasites. New strategies for the control of nematode
      infections are needed to prevent diarrhoea and dag formation in adult sheep.

PMID- 7726761
TI  - Tackling the knowledge explosion without overloading the student.
AB  - Assessment of today's approach to veterinary education reveals a system
      overloaded with facts and students stressed to memorise and recall medical
      information. The Mississippi State University College of Veterinary Medicine has
      chartered a path to reduce the curricular information overload. The innovative
      incorporation of computers into the curriculum coupled with problem-based
      learning activities are preparing students to find information and learn on their
      own.

PMID- 7726762
TI  - Relationships between electrocardiographic findings, racing performance and
      training in standardbred horses.
AB  - The presence of abnormal T waves in three or more electrocardiographic leads has
      been used to diagnose the cause of poor race performance in horses. This study
      investigated the relationship between previous racing performance in Standardbred
      horses and T waves, and the effect of training on the T wave. Thirty-two horses
      were electrocardiographed in two Sydney racing stables. Sixteen horses (50%) had
      ECGs with three or more leads with abnormal T waves, and these horses had won
      more races, had a greater ratio of wins per start and a greater number of dollars
      earned per start than horses with less than three abnormal T waves (P < 0.05).
      Horses with abnormal T waves also had significantly faster racing times (P <
      0.01). There were significant (P < 0.01) correlations between the number of
      abnormal T waves and both number of wins (R = 0.47) and dollars earned per start
      (R = 0.45). Fastest winning mile rate was also negatively correlated with number
      of leads with abnormal T waves (R = -0.52, P < 0.01). Twenty two horses were also
      electrocardiographed within seven days of good racing performance. The mean
      number of abnormal T waves was 2.7 +/- 0.41, and the mean T wave amplitude in the
      four chest leads (CV, CR, CL, CF) was 0.9 +/- 0.15 mV. Thirteen horses (59%) had
      abnormal T waves in three or more leads. The effect of training on the T wave was
      also investigated in nine previously untrained and unraced Standardbred
      racehorses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726763
TI  - Reconstruction of a maxillary sinus defect in a horse using a levator
      nasolabialis muscle flap.

PMID- 7726764
TI  - The effects of moxidectin against natural infestations of the cattle tick
      (Boophilus microplus).

PMID- 7726765
TI  - The influence of anticoagulant, storage temperature and time on equine plasma
      lactate concentration.

PMID- 7726766
TI  - Antigenic relationship of the picorna-like virus of larval barramundi, Lates
      calcarifer Bloch to the nodavirus of larval striped jack, Pseudocaranx dentex
      (Bloch & Schneider).

PMID- 7726767
TI  - The prevalence of Streptococcus suis type 2 in Western Australian piggeries.

PMID- 7726768
TI  - Rabbit haemorrhagic disease virus.

PMID- 7726770
TI  - Dunlop Asia Awards.

PMID- 7726769
TI  - A comparison of stress in surgically and non-surgically mulesed sheep.

PMID- 7726771
TI  - The fate of eyewear in aircraft ejections.
AB  - Ejection from jet aircraft has been exhaustively studied from many perspectives;
      e.g., causes of ejection, types and causes of ejection injuries, etc. Curiously,
      no reports exist describing the fate of eyewear in ejections. Many pilots wear
      required corrective lenses during flight operations, and many wear tinted lenses.
      What happens to these during ejection? What injuries are a result of the eyewear?
      What factors can be identified that influence retention of the eyewear and
      severity of related injury? Do contact lenses provide significant advantages?
      There were 48 ejections occurring between 1977 and 1990 that involved corrective
      or tinted lens use that were retrospectively examined using Naval Safety Center
      records and personal questionnaires. There were five contact lens wearers
      included. Retention rates were calculated as functions of several variables.
      Although 37 of 46 lost all lenses, each instance of retention occurred with visor
      down, oxygen mask on, helmet properly secured, and at lower ejection speeds.
      Related injuries were minor and occurred in only 20%. The utility and need for
      enforcement of standard operating procedures (i.e., mask on, helmet secured, and
      visor down) was clearly demonstrated. Only 19 of 46 clearly met all 3 criteria.
      Contact lens users were too few to allow meaningful conclusions.

PMID- 7726772
TI  - Neuroendocrine responses to real and simulated BA Hawk MK 51 flight.
AB  - The effects of psychological workload on the plasma levels of eight
      neuroendocrine hormones were studied in 5 undergraduate and 5 senior military
      pilots of the Finnish Air Force (FAF). All subjects performed the same short-term
      basic flight mission, which included the following: 1) start; 2) ILS-approach in
      minimum weather conditions; 3) visual approach; and 4) landing. The mission was
      performed twice: first with the BA Hawk MK 51 simulator with minimal G-forces and
      after that with a BA Hawk MK 51 jet trainer with Gz-forces below +2. Blood
      samples were collected 30 min before and 10 min after the mission and were
      measured for adrenaline, noradrenaline, ACTH, beta-endorphin, prolactin,
      vasopressin (AVP), atrial natriuretic peptide (ANP), and cortisol. The plasma
      levels of adrenaline, noradrenaline, ACTH, beta-endorphin, and cortisol did not
      change significantly in response to simulated or real flight. Plasma prolactin
      levels increased significantly (p = 0.037) in all subjects after the mission
      performed with jet trainer, and the increase was especially great in cadets.
      However, the same mission performed with the simulator did not raise plasma
      prolactin levels. This finding suggests that the psychological workload in a
      flight simulator does not correspond to the psychological workload in a real jet
      trainer, at least not in basic flying. Plasma AVP increased significantly (p =
      0.032) after the mission performed with the simulator in cadets; this increase
      can be described as a "first-time effect." Plasma ANP also increased
      significantly (p < 0.05) after a real jet trainer flight.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7726773
TI  - The psycho-physiological response to parachuting among novice and experienced
      parachutists.
AB  - Elevated heart rate and increased anxiety are two indicators of stress. This
      study investigated the heart rate and anxiety response to parachuting among seven
      novice and six experienced parachutists. Heart rate was measured from the moment
      of boarding the aircraft until landing. Anxiety was measured prior to boarding
      the aircraft. Heart rate was significantly higher among the novice compared to
      the experienced parachutists, especially during takeoff (125 +/- 11 vs. 95 +/- 17
      beats.min-1, respectively), and upon exit or free fall (184 +/- 12 vs. 164 +/- 17
      beats.min-1, respectively). However, due to the difference in ages between the
      groups, when expressed relative to maximal heart rate, there was no difference in
      the heart rate response between groups (e.g., exit/free fall: 93.0 +/- 5.5% vs.
      88.4 +/- 7.8% for novice and experienced, respectively). No statistical
      differences were observed in the anxiety scores between groups, although the
      novice parachutists scored somewhat higher (16.0 +/- 3.7 vs. 12.5 +/- 5.7,
      respectively). A significant correlation (r = 0.72) was observed between heart
      rate upon landing and the state anxiety scores. These results demonstrate a high
      psycho-physiological stress response to parachuting among both novice and
      experienced parachutists. It is likely that novice parachutists are stressed to a
      higher degree and may therefore be more prone to performance-related injury
      (e.g., upon landing). However, since both groups reached a similar percentage of
      their maximal heart rate, they may be at a similar risk of cardiac injury.

PMID- 7726774
TI  - Evaluation of integrated night vision goggle (NVG) helmets under sustained +Gz.
AB  - Three integrated night vision goggle (NVG) helmets from different manufacturers
      were evaluated under high-G conditions. Structural and operational integrity, as
      well as neck forces in pounds, were determined via instrumented manikin testing
      before human exposure with the helmets during sustained +Gz. Results of the
      manikin testing showed that the helmets could withstand the rigors of high-G, and
      that predicted forces (using helmet weights and centers-of-gravity) matched those
      obtained experimentally from load cells in the x-axis of the manikin's neck.
      After manikin testing, 10 subjects were randomly exposed to four different high-G
      profiles on the Dynamic Environmental Simulator (DES) man-rated centrifuge
      located at Wright-Patterson AFB, OH: gradual onset to +8 Gz, a simulated aerial
      combat maneuver (SACM) profile, and two +4 Gz profiles, one with the mask
      dangling from the helmet and the other with the mask removed. Fit assessments
      were conducted before high-G exposure, and one helmet was affected significantly
      by failure of fit. The degree of migration of the NVG intensified image away from
      the eyes was affected most by the following helmet characteristics: design of the
      nape strap, size of the NVG image provided by each helmet system, goodness of
      helmet fit, and the use of the mask as a stabilizer. Although neck strength of
      each subject was measured and compared to the degree of head stability while
      wearing each helmet, no effects were found. However, subjects were not allowed to
      perform fast, high-amplitude head movements in the centrifuge for safety
      reasons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7726775
TI  - Inflight arterial saturation: continuous monitoring by pulse oximetry.
AB  - The ability of newer airliners to fly at higher altitudes has resulted in an
      increased altitude exposure to both airline crews and passengers. This increase
      in altitude exposure has the potential to place some individuals at risk for
      desaturation. Using pulse oximetry, the arterial oxygen saturation of 42 airline
      crew members was continuously monitored on 22 regularly scheduled commercial
      flights. Mean nadir arterial oxygen saturations fell from 97.0% preflight to
      88.6% at cruising altitudes. Pulse oximetry results revealed large variations
      between individuals. Individual nadir saturations ranged from 93% to 80%. Modern
      aircraft flight may result in desaturations even among healthy aircrew. The
      effects on human performance remain unknown.

PMID- 7726776
TI  - Femoral flow response to lower body negative pressure: an orthostatic tolerance
      test.
AB  - The objective was to check, during a lower body negative pressure (LBNP) test,
      new vascular parameters for the detection of orthostatic intolerance induced by
      head-down-tilt (HDT) and spaceflight. METHODS: The lower-limb volume flow and
      vascular resistance were evaluated by Doppler ultrasound. The HDT population
      consisted of two groups: control [6 subjects resting in a HDT (-6 degrees)
      position for 28 d] and countermeasure (6 subjects also in HDT for 28 d, but with
      repeated LBNP and exercise). The LBNP orthostatic test (four steps: -20, -30, 
      40, -50 mm Hg, of 3 min each) was performed before, during, and after the HDT.
      For the 14-d spaceflight (Antares) the cosmonaut underwent the LBNP test (10 min
      at -25 mm Hg and 10 min at -45 mm Hg), at preflight (3 times), inflight (day 11),
      and postflight (twice). RESULTS: HDT--As the LBNP pressure decreased, the femoral
      blood flow decreased and the lower-limb vascular resistances increased in both
      HDT groups. In the control group the femoral flow was less reduced, at each of
      the 4 levels of depressure (p < 0.01). The amplitude of the leg vascular
      resistances was reduced at -40 mm Hg, and at -50 mm Hg, on HDT day 15 in both
      groups (before LBNP, after 1 week's exercise for the countermeasure group), and
      on post-HDT day 1 (p < 0.01) only in the control group. The femoral vascular
      resistance response had completely recovered in the countermeasure group on post
      HDT day 1. During the post-HDT tilt table test, all 6 controls had a drop in
      blood pressure of 20 mm Hg (4 subjects) or 10 mm Hg (2 subjects); 3 had pre
      syncopal symptoms. The HDT countermeasure subjects had neither any clinical signs
      of orthostatic intolerance nor any blood pressure drop. 14d-Spaceflight--During
      the flight, the cosmonaut did not use any countermeasures (exercise, LBNP). On
      flight day +11, and on postflight day 3, the femoral vascular resistance response
      to LBNP was decreased as observed in the control group on HDT day +15 and post
      HDT. On postflight day 7, the femoral response had completely recovered. The
      middle cerebral flow response to the various pre-, in-, and postflight LBNP tests
      consisted of a slight decrease of the cerebral flow together with resistances of
      comparable amplitude (-10 to -20%) to those measured during the same LBNP test in
      the HDT control group. CONCLUSION: The femoral hemodynamics are much more
      disturbed than the cerebral ones in vascular deconditioning. The assessment of
      the lower limb vascular reactivity will be of interest in predicting orthostatic
      intolerance, and checking the efficiency of counter-measures.

PMID- 7726777
TI  - Physiological responses of rhesus monkeys to exercise at varied temperatures.
AB  - This research characterizes the effects of selected physiological stressors such
      as work and various environmental heat loads in rhesus monkeys. Non-human
      primates (N = 6) were behaviorally conditioned to exercise in a wheel ergometer
      at approximately 3 METs (1 MET = 3.5 ml O2 uptake.kg-1.min-1). On separate days,
      each monkey attempted six work/rest cycles (10 min work: 1 min rest) at 15, 25,
      and 35 degrees C (Tdb), vapor pressure < 10 mm Hg. Core temperature (Tco), body
      weight (BW) and blood samples were taken immediately before and after exercise.
      Excessively high heat storage rates dictated that the 35 degrees C trial be
      limited to three work/rest bouts. The change in Tco during exercise was
      significantly greater in the 35 degrees C trial than during the 15 and 25 degrees
      C work bouts. Sweat rate, as determined by the change in BW over time, was also
      significantly greater during the 35 degrees C trial as compared to the 15 and 25
      degrees C trials. Glucose levels (mean +/- SE) declined significantly during
      exercise from 4.35 +/- 0.1 and 4.58 +/- 0.4 mmol to surprisingly low levels of
      1.67 +/- 0.2 and 1.76 +/- 0.2 mmol in the 15 and 25 degrees C trials,
      respectively. Increases in blood lactate, glycerol, and triglycerides were
      observed independent of environmental temperature. Free fatty acids increased
      during exercise in the 15 and 25 degrees C trials but declined slightly during
      the shorter 35 degrees C trial. The findings of this study indicate that the
      increased heat storage observed at higher environmental heat loads appears to
      substantially limit the amount of work these primates can perform, possibly the
      result of a limited sweat production capacity. Additionally, plasma glucose
      following exercise decreased to levels not typically seen in humans. The general
      metabolic profile in these primates was otherwise similar to that observed in
      humans at this work level.

PMID- 7726778
TI  - Splenic effects on hemodynamics induced by hypothermia and rewarming in miniature
      swine.
AB  - Central arterial hemodynamic changes were assessed during cooling, hypothermia,
      and rewarming in splenectomized (SPX, n = 4) and unsplenectomized (SP, n = 4) 8
      10 month old male Yucatan miniature swine (34.0 +/- 1.4 kg). Under isoflurane
      anesthesia, and using circulating-water blankets, pigs were cooled to and then
      maintained for 2 h at a rectal temperature (Tre) of 27 +/- 1 degrees C;
      hypothermia was followed by rewarming to normothermia (37 +/- 1 degrees C). There
      were significantly (p < or = 0.05) greater changes in central arterial hematocrit
      and hemoglobin (delta HCT and delta HGB) from respective precooling baseline
      levels in the SP group during hypothermia and early rewarming (SP: delta HCTmax =
      9-10%RBC, and delta HGBmax = 3.0-3.5 g/dl vs. SPX: delta HCTmax = 3-4%RBC, and
      delta HGBmax = 1.5-1.8 g/dl). By the end of rewarming, splenic resequestration
      and extravascular fluid shifts resulted in these values returning to baseline. In
      addition, cardiovascular instability was seen in the SPX group compared to the SP
      animals as evidenced by significant tachycardia and hypotension during rewarming.
      We have concluded from these studies that hypothermia causes significant
      hemoconcentration, and that splenic contraction is the major cause of this
      hemoconcentration during hypothermia and initial rewarming in miniature swine. A
      splenectomized design should be considered for swine studies that purport to
      pattern human pathophysiology, especially for modelling rewarming shock.

PMID- 7726779
TI  - Symptoms of infection and altitude illness among hikers in the Mount Everest
      region of Nepal.
AB  - Symptoms of acute mountain sickness (AMS) and infection were recorded daily in
      283 hikers walking the Mount Everest base camp trek in the Nepal Himalaya. Some
      57% of subjects developed AMS, and 87% experienced at least one symptom of
      infection during the study period. Coryza (75%), cough (42%), sore throat (39%),
      and diarrhea (36%) were especially prevalent. All symptoms of infection were more
      prevalent among those with AMS. The incidence of AMS was greater among those with
      more symptoms of infection (p = 0.00004), and the number of symptoms of infection
      experienced with positively correlated with AMS score (rs = 0.43, 95% CI = 0.33
      to 0.52). These results suggest that symptoms of infection are common at high
      altitude and are associated with a higher incidence of AMS. People with
      infections should ascend at a slower rate at high altitude.

PMID- 7726780
TI  - The crash of the Partnair Convair 340/580 in the Skagerrak: traumatological
      aspects.
AB  - In September 1989 an aircraft carrying 55 people crashed into the sea north of
      Denmark. There was no warning of the crash. The medico-legal investigation of the
      accident concentrated on finding clues to the cause of the accident, and
      identifying the victims, all of whom perished. These were found in two groups--31
      were immediately recovered from the surface of the sea and 19 were collected from
      the sea or shore during the following months. The injuries in the two groups
      differed, indicating that the aircraft broke up in mid-air. One group probably
      fell into the sea after a free fall, while the other probably remained in the
      wreckage until hitting the surface. The victims' injuries showed no evidence of
      fire or explosion. The technical investigators concluded that the aircraft broke
      up due to a structural failure in the tail.

PMID- 7726781
TI  - The crash of the Partnair Convair 340/580 in the Skagerrak: identification of the
      deceased.
AB  - In 1989, a Norwegian Convair aircraft crashed into the sea near the northwest
      coast of Jutland. Apparently, the aircraft had disintegrated in midair. On board
      were 50 passengers and a crew of 5. There were no survivors. Immediately after
      the crash 31 bodies were found. During the next 10 days, 11 bodies were recovered
      from the seabed and within the next 6 months, a further 8 bodies were found. Five
      bodies were never recovered. All the bodies found were positively identified
      based on personal effects combined with medical and dental findings. Different
      models for cooperation between the Primary ID-group, who were responsible for the
      final identification, and the ID-teams, who performed the examination of the
      bodies, were tested. It was concluded that the fastest and most reliable results
      were obtained when the ID-teams responsible for the examination of the bodies
      also took part in the reconciliation sessions.

PMID- 7726782
TI  - Acute effects of cigarette smoking withdrawal: a review of the literature.
AB  - Smoking among commercial and military aviators is a health hazard in the cockpit.
      Pilots who are required to abstain before and during flight may suffer cockpit
      performance decrements. This study reviews the physiological, cognitive,
      behavioral, and psychological effects of smoking withdrawal as they relate to
      flying performance. The variety of research designs, methodologies, and subject
      groups is discussed. Findings suggest that heart rate, arousal, vasoconstriction,
      vigilance, concentration, and energy increase with nicotine use; stress and
      irritability are reduced with smoking. Withdrawal, on the other hand, produces a
      decrease in carboxyhemoglobin, digit recall, serial addition/subtraction, and job
      satisfaction; blood pressure, depression, absenteeism, caloric intake, craving,
      aggressiveness, confusion, and impulsivity increase with withdrawal. Severity of
      withdrawal symptoms varied, but most studies report psychological, and/or
      physiological responses to nicotine withdrawal. The conflict between health and
      performance is discussed and suggestions for future directions are offered.

PMID- 7726783
TI  - Nathan Zuntz (1847-1920)--a German pioneer in high altitude physiology and
      aviation medicine, Part I: Biography.
AB  - Nathan Zuntz (1847-1920) was a key person in the history of high altitude
      physiology and aviation medicine. As a professor of animal physiology at the
      Landwirtschaftliche Hochschule (Agricultural University) in Berlin from 1881
      until 1918, he carried out laboratory studies on the changes in metabolism at
      rest and during exercise. To this end he, together with August Julius Geppert,
      developed the famous "Zuntz-Geppert'schen Respirationsapparat" (Zuntz-Geppert
      respiratory apparatus) in 1885. In the early 1890's, Zuntz extended his research
      to the field of high altitude physiology. In view of the variety of questions,
      and despite considerable methodological problems, Zuntz first studied the effects
      of lowered PO2 on the human body in a Pneumatischen Kammer (hypobaric chamber).
      In 1893 the newly completed Capanna Regina Margherita, an international research
      station at the top of Monte Rosa, Italy (4,500 m), became the site of Zuntz's
      extensive field studies, where he worked together with his close co-worker Adolf
      Loewy (1862-1936), the Italian Angelo Mosso (1846-1910), and the Austrian Arnold
      Durig (1872-1961). For their investigations Zuntz invented the transportable
      Gasuhr (a gas exchange measuring device). In 1902 Zuntz and the Austrian Hermann
      von Schroetter (1870-1928) made two balloon ascents up to 5,000 m in Berlin. A
      synopsis of these studies was published by Zuntz in 1906: his famous book
      "Hohenklima und Bergwanderungen" (High altitude climate and mountain-touring). A
      few years later Zuntz undertook further expeditions to the Canary Islands (Pico
      de Teide), conducting studies in airships and planes until 1914. Zuntz retired in
      1916 and died in Berlin on March 22, 1920.

PMID- 7726784
TI  - Nathan Zuntz (1847-1920)--a German pioneer in high altitude physiology and
      aviation medicine, Part II: Scientific work.
AB  - For over 52 years, the work of Nathan Zuntz (1847-1920) covered an amazingly wide
      spectrum of research fields; metabolism, nutrition, respiration, blood gases,
      exercise, and high altitude physiology were the main themes. Zuntz achieved fame
      for his invention of the Zuntz-Geppert respiratory apparatus in 1886 and the
      first Laufband (treadmill) in 1889. To this experimental setup Zuntz later added
      an X-ray apparatus in 1914 to determine the changes in heart volume during
      exercise. Moreover, he constructed a climate chamber to study exercise under
      varying and sometimes extreme climates. For field studies Zuntz invented a
      transportable Gasuhr (dry gas measuring device). Zuntz was the first to describe
      the difference between laboratory data gained in a hypobaric chamber and the
      measurements at high altitude. He found that the barometric formula is not
      applicable in the field. Two balloon expeditions in 1902 by Zuntz and his pupil,
      v. Schroetter, marked the step from terrestrial physiology towards aviation
      medicine. An outline of the development of scientific aviation in Berlin from
      1880-1918 elucidates how closely the aviation union, army, and scientific
      departments were connected with and dependent upon each other. In cooperation
      with these institutions Zuntz and v. Schroetter constructed an oxygen supply
      system and planned a pressure cabin for extreme altitudes above 10,000 m, a
      forerunner of modern systems in aviation and astronautics. In 1912, Zuntz and v.
      Schroetter each published papers on aviation medicine, both publications
      internationally unique in style and extent. Zuntz's work in its empirical
      approach was the counterpart to the established formal mathematical-physical
      reductionism of the German Physiological Society.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7726785
TI  - Cases from the aerospace medicine residents' teaching file. Case #61. A case of
      varicella.

PMID- 7726786
TI  - Flight nursing: a unique experience.

PMID- 7726787
TI  - Call for national center(s) of excellence for aerospace medicine.

PMID- 7726788
TI  - You're the flight surgeon. Nontender neck mass.

PMID- 7726789
TI  - You're the flight surgeon. Dengue fever.

PMID- 7726790
TI  - You're the flight surgeon. Migraine.

PMID- 7726791
TI  - Factors related to pilot survival in helicopter commuter and air taxi crashes.
AB  - We examined factors related to pilot survival in 167 consecutive helicopter
      commuter and air taxi crashes that occurred during 1983-88. Case fatality rates
      and adjusted odds ratios from multivariate logistic regression models were
      determined using data from the National Transportation Safety Board (NTSB).
      During this 6-year period, 29 pilots-in-command died in 167 helicopter commuter
      and air taxi crashes, a case fatality rate of 17.4%. Factors significantly
      associated with increased risk of pilot fatality were aircraft fire [odds ratio
      (OR) 20.0, 95% confidence interval (CI) 4.6-86.8], not using shoulder harnesses
      (OR 9.2, 95% CI 2.2-37.3), and aircraft with two engines (OR 4.8, 95% CI 1.3
      17.4). In addition, we present data regarding success and failure of emergency
      flotation devices. The results suggest that the likelihood of pilot survival in
      helicopter crashes could be greatly improved by preventing crash associated fires
      and promoting the usage of shoulder restraints.

PMID- 7726792
TI  - The basis of autoimmunity: an overview.
AB  - Autoimmune diseases represent a failure of control in the immune system. In
      recent years, our understanding of the mechanisms of action of both the innate
      and the specific immune responses has increased greatly. In particular, we now
      know much more about the nature of antigens recognized by lymphocytes, as well as
      how diversity of antigen receptors is generated, antigens and antigen receptors
      interact, and the cells of the immune system communicate. It is apparent that an
      inevitable consequence of the diversity of the potential response to antigen is
      self-reactivity. However, the relative infrequency with which pathological self
      reactivity occurs implies the existence of effective control of immune responses.
      The conditions under which immune responses can be activated, and the factors
      which regulate their progression, have been subjected to detailed scrutiny.
      Several of the mechanisms involved in the removal or inactivation of self
      reactive lymphocytes, the process of self-tolerance, are now understood. What is
      less clear are the conditions under which, and the mechanisms by which, this self
      tolerance can break down, giving rise to autoimmunity. Several classes of
      explanation have been put forward to explain this failure of self-tolerance.
      Although they are of great theoretical interest, proof of their involvement in
      the pathogenesis of the major autoimmune diseases is largely lacking. A further
      expansion of our understanding of the mechanisms by which self-tolerance is
      normally maintained is still needed, in order to comprehend the pathways of
      breakdown of this tolerance in autoimmunity. Only then will sites and mechanisms
      for effective therapeutic intervention be identified.

PMID- 7726794
TI  - Pregnancy and autoimmune endocrine disease.

PMID- 7726793
TI  - Thyroid-associated ophthalmopathy: pathogenesis and clinical management.
AB  - The pathogenesis of thyroid-associated ophthalmopathy is autoimmune. The
      questions to which answers are eagerly awaited are the identification of the
      autoantigen(s) and the definition of the autoimmune processes (cellular or
      humoral) responsible. Cellular and humoral immune responses and modulation by
      cytokines, against orbital tissues have been described. A link between the
      thyroid and the orbit seems inevitable, possibly in the form of a cross-reactive
      antigen, and top of the list of candidate antigens is the TSH receptor. Optimal
      treatment of TAO necessitates careful assessment. Thoughtful planning and timing
      and choice of intervention with conventional therapies, can lead to satisfactory
      results in the majority of cases. In addition to treating the severe
      complications, such as optic neuropathy, corneal exposure and muscle
      misalignment, corrective surgery to reconstruct the appearance of the patient's
      eyes should be made available.

PMID- 7726795
TI  - Autoimmunity to steroid-producing cells and familial polyendocrine autoimmunity.
AB  - New insights into the autoimmune basis for Addison's disease have come from
      identification of at least three P450 cytochrome enzymes as autoantigens, each
      having distinct associations with Addison's disease as part of the APS type 1 or
      2 syndrome. Enzymes are tissue-restricted proteins which are the frequent targets
      of autoimmunity in other organ-specific diseases (Editorial, 1992), and it seems
      likely that further P450 enzymes could be involved in the pathogenesis of other
      components of these syndromes. How adrenal damage is initiated remains unclear.
      Adrenal autoantibodies may have a pathogenic role, as yet obscure, or could arise
      secondary to T cell-mediated tissue damage, although it seems highly likely that
      the same autoantigen provokes cell-mediated and humoral autoimmunity. Sharing of
      autoantigens between ovary and adrenal glands, particularly the side-chain
      cleavage enzyme, is one explanation for the close association of ovarian failure
      and Addison's disease, but other, more common forms of ovarian autoimmune disease
      exist. Their further definition will come from identification of the autoantigens
      involved. By analogy with animal models, T cell-mediated injury is likely to be
      central to pathogenesis. The evidence for antibodies blocking hormone receptors
      in premature ovarian failure is meagre at present, but the availability of
      recombinant LH and FSH receptors should clarify this issue. HLA-DR3 is associated
      with almost all autoimmune endocrinopathies, and this is particularly striking in
      APS type 2. However, there is no such association with APS type 1; the most
      likely genetic candidate in this condition is at a locus controlling T cell
      development. Although the adrenal and ovarian autoimmune processes in APS type 1
      and 2 may be distinct, the characterization of the gene involved in APS type 1
      will have major implications for our understanding of autoimmune endocrine
      disease.

PMID- 7726796
TI  - Animal models of autoimmune endocrine disease and their uses in developing new
      methods of intervention.
AB  - This review provides basic information concerning the major animal models in use
      for the study of autoimmune endocrine diseases (AEDs). Although several other
      models exist which parallel human AEDs such as autoimmune orchitis, most research
      in this area has centred on animal models of insulin-dependent diabetes mellitus
      (IDDM) and thyroiditis. These models, between them, appear to exhibit most of the
      disease manifestations of their human counterparts and thereby permit the study
      of possible methods of intervention in the disease process. While no one model
      represents a perfect correlation with the human disease it represents, common
      characteristics are recognizable between them. For instance, the central role of
      activated T cells in controlling the disease process. The chapter continues by
      examining the various ways in which models of autoimmunity, specifically IDDM and
      experimental allergic thyroiditis (EAT), have been used to investigate the
      possibility of preventing or arresting autoimmune destruction. Several different
      approaches are described that illustrate the variety of techniques that have
      proven both potentially, or in reality, effective and those that have proven less
      efficacious than first hoped.

PMID- 7726797
TI  - Pathogenesis of insulin-dependent diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus is strongly associated with certain HLA types
      and the presence of islet cell-specific autoantibodies. The pathogenesis is a
      specific loss of pancreatic beta cells. The dissection of IDDM genes is
      complicated by the low recurrence rate of the disease among first-degree
      relatives. HLA-DQ2 and 8 are closest to IDDM with a marked synergistic effect of
      DQ2/8 heterozygotes. The associations with other HLA genes are often explained by
      linkage disequilibrium. Genetic factors on other chromosomes which influence the
      pathogenesis are still to be fully identified but candidates are on chromosomes
      11 (insulin gene polymorphisms) and 7 (TCR gene polymorphisms). The
      autoreactivity against the GAD65 isoform is pronounced both before and at the
      clinical onset of IDDM. GAD65 autoantibodies show the highest predictive value
      and may represent an initiating autoantigen. Autoantibodies to numerous other
      beta cell autoantigens are detected at the clinical onset but may represent a
      secondary response and antigen spreading during a sustained autoimmune attack on
      the beta cells. The role of T cells in human IDDM is yet to be defined. GAD65 and
      other islet autoantibodies have a low positive predictive value for IDDM and
      further investigations are needed to clarify ways to predict IDDM in the general
      population.

PMID- 7726798
TI  - Infections and autoimmune endocrine disease.
AB  - The literature examined in this review points to the possible involvement of
      infectious agents in the pathogenesis of autoimmune endocrine diseases, primarily
      autoimmune thyroid disease and diabetes mellitus. Various mechanisms have been
      proposed to explain induction of autoimmunity by infection but it seems that
      three possibilities may be important in individuals susceptible to developing
      autoimmune disease: molecular mimicry (perhaps to retroviruses); polyclonal T
      cell activation (by an endogenous superantigen or an infecting organism); and MHC
      class II antigen induction. It seems reasonable that all three mechanisms operate
      together or separately in different individuals. Data continue to accumulate in
      favour of infectious agents being important initiators of autoimmune disease.

PMID- 7726799
TI  - Cellular immunity in autoimmune thyroid disease.
AB  - Autoimmune thyroid disease occurs in a genetically susceptible patient after
      triggering events including bacterial and viral infections, environmental
      insults, drugs or hormones. These triggering events may break the tolerance to
      self-antigen, leading to emergence of autoreactive T cells. One or more T cell
      clones that recognize the self-antigen is(are) assumed to be involved in
      initiating autoimmune processes. Following this, T cell clones expand and migrate
      from the peripheral blood into the thyroid gland. Migration of mononuclear cells
      is controlled by inflammatory cytokines and adhesion molecules. Intrathyroidal T
      cells may interact with dendritic-like cells, thyrocytes expressed with HLA-DR
      antigens, B cells and extracellular matrix, resulting in the proliferation of T
      cells, production of cytokines and autoantibodies. These interactions are also
      regulated by inflammatory cytokines and adhesion molecules. When the initial
      immune response is completed, a secondary immune response ensues, that may be of
      considerable complexity involving reaction of infiltrating T cells to a variety
      of tissue-specific and tissue-non-specific antigens. These immune responses may
      contribute to the recurring immunologic activity and maintenance of autoantibody
      overproduction.

PMID- 7726800
TI  - The thyrotropin receptor as a model to illustrate receptor and receptor antibody
      diseases.
AB  - The thyrotropin receptor (TSHR) has been used as an example to illustrate how
      disease may be the consequence of: 1. Modifications or inappropriate production
      of the natural ligand. 2. Production of abnormal agonists or antagonists such as
      autoantibodies. 3. Modifications in receptor structure resulting in constitutive
      activation or the absence of activation following ligand binding. 4. Changes in
      the cellular machinery which transduces the signal from the receptor to the
      cytoplasmic or nuclear endpoint target. This chapter concentrates on mechanisms
      (2) and (3). Since the cloning of the TSHR it has been shown that approximately
      50% of cases of toxic adenoma can be explained by somatic point mutations in the
      nucleotide sequence of the receptor gene which causes single amino acid
      substitutions. The resulting modified TSHR structure constitutively activates
      adenylate cyclase (via Gs), intracellular cAMP levels are increased and, since
      cAMP controls both growth and function of the human thyrocyte clonal expansion of
      the mutated cell ensues. Similarly, activating mutations of the TSH receptor gene
      in the germline are responsible for hereditary hyperthyroidism with goitre, which
      is transmitted in the autosomal dominant mode. Changes in receptor primary
      structure, i.e. a modified autoantigen, do not seem to be responsible for the
      escape from tolerance which must precede production of thyroid stimulating
      antibodies (TSAB) which cause hyperthyroid Graves' disease and thyroid blocking
      antibodies (TBAB) which are responsible for some cases of hypothyroid idiopathic
      myxoedema. The eukaryotic expression of wild-type, experimentally mutated and
      chimeric TSHR has enabled some progress in delineating the residues involved in
      binding TSH, TSAB and TBAB. All three ligands bind numerous discontinuous
      residues in the extracellular domain of the receptor. The difference between the
      bioactivity of TSAB and TBAB cannot be explained completely by different binding
      sites on the receptor. Subtle differences in, for example, glycosylation and
      sialation of the immunoglobulins may be implicated, since bioactivity of TSH
      itself seems to depend on these. Attempts to define T cell epitopes have not
      identified a major immunogenic region. Indeed heterogeneity seems to be a
      hallmark of TSHR autoantibodies (TRAB). The possibility that thyroid-associated
      ophthalmopathy and pretibial myxoedema may be receptor antibody diseases is
      discussed. Further progress awaits large-scale production of TSHR able to bind
      TSH to facilitate X-ray crystallographic studies, the development of specific T
      cell clones and the cloning of TSAB autoantibodies.

PMID- 7726801
TI  - Anxiety sensitivity: theoretical perspectives and recent findings.
AB  - Anxiety sensitivity (AS) is the fear of anxiety-related sensations, which arises
      from beliefs that these sensations have harmful somatic, psychological or social
      consequences. According to Reiss (1991), AS is one of three fundamental fears
      that amplify or cause many common fears. AS also is thought to play an important
      role in causing panic attacks. The purpose of the present article is to review
      recent findings concerning the construct of AS and its place in the nomological
      network outlined by Reiss. Although the weight of evidence supports a
      unifactorial model of AS, recent findings suggest AS is multifactorial at the
      level of first-order factors, and these factors load on a single higher-order
      factor. People with elevated AS, compared to those with low AS, are more likely
      to have histories of panic attacks. AS is factorially distinct from other
      fundamental fears, and is more strongly related to agoraphobia than other common
      fears. AS can be regarded as a subfactor of trait anxiety, and is more strongly
      related to agoraphobia than other common fears. AS can be regarded as a subfactor
      of trait anxiety, although the question arises as to whether AS is a cause of
      trait anxiety. Important questions for further investigation concern the etiology
      of AS and whether it can be reduced to still more basic fears.

PMID- 7726802
TI  - The treatment of social phobia: the differential effectiveness of exposure in
      vivo and an integration of exposure in vivo, rational emotive therapy and social
      skills training.
AB  - Thirty-four social phobic patients were treated with either exposure in vivo or
      an integrated treatment, consisting of rational emotive therapy, social skills
      training and exposure in vivo. Comparison with a waiting-list control group
      showed the effectiveness of both treatments. Contrary to expectations, the
      integrated approach was not superior over exposure in vivo alone. Also, the long
      term effectiveness of both treatments was equally good.

PMID- 7726803
TI  - Child, parent and family dysfunction as predictors of outcome in cognitive
      behavioral treatment of antisocial children.
AB  - The present study examined factors that predicted favorable treatment outcomes
      among clinically referred conduct problem children (N = 105, ages 7-13) who
      received cognitive-behavioral treatment. Three domains (severity and breadth of
      child impairment, parent stress and psychopathology and family dysfunction)
      assessed at pretreatment were predicted to affect treatment outcome. The results
      only partially supported the prediction. Less dysfunction in each of the domains
      predicted who responded favorably to treatment on parent ratings of deviance and
      prosocial functioning but not on teacher ratings of these outcomes. The findings
      have implications for identifying youths who respond to available treatments. The
      results also underscore fundamental questions about the assessment of treatment
      effects and the criteria for evaluating outcome.

PMID- 7726805
TI  - Effect of psychological treatment on cognitive bias in generalized anxiety
      disorder.
AB  - Measures of attention and implicit memory for threatening words were obtained
      from anxious patients before and after psychological treatment, and compared with
      data from non-anxious control Ss collected over the same period. Findings
      confirmed the expectation that the presence of threatening distractors would be
      associated with greater interference with the performance of anxious patients
      than with that of controls, in both color-naming and attentional search tasks,
      but failed to confirm the previous finding of related differences in priming on a
      word completion task. Treatment significantly reduced selective interference
      effects in anxious patients, and abolished evidence of differences between the
      treated patients and controls. It is suggested that cognitive bias effects in
      anxiety may either depend on state factors alone, or may represent a more
      enduring individual difference that becomes apparent only when vulnerable
      individuals are primed by mood state or stressful events.

PMID- 7726806
TI  - Memory bias does not generalize across anxiety disorders.
AB  - Individuals with social phobia were compared with normal controls on their memory
      for socially-related threat words in contrast to positive and neutral words. A
      memory paradigm used in a previous study of panic disorder patients [Cloitre, M.
      & Liebowitz, M. R. (1991) Cognitive Therapy and Research, 15, 609-619] was
      applied to test the generalizability of findings of threat-biased memory in a
      semantic memory task (free recall) and a perceptual memory task (high-speed
      recognition) to social phobics. No evidence of threat-related memory bias among
      social phobics was obtained. Since both the social phobic and control groups
      showed better memory for affectively valenced (threat and positive) compared to
      neutral information, it is unlikely that the absence of threat-biased memory
      among social phobics was the result of insensitive measurement.

PMID- 7726804
TI  - An evaluation of a behavioural treatment approach to hearing impairment.
AB  - Twenty-four elderly hearing impaired Ss participated in an experimental treatment
      study and received either behavioural group treatment or served as untreated
      controls. The treatment package included applied relaxation, video self
      modelling, exposure, information and various coping skills. Assessments (pre
      post) were conducted using a structured video-interview measuring coping
      behaviour. In order to evoke behavioural compensation small acoustic provocations
      were included in the interview. The edited videos were then rated blindly by two
      trained observers. Pre-post assessments also included daily registered hearing
      problems on visual analogue scales and a questionnaire. Finally, a one month
      follow-up blind telephone interview was conducted. Results showed significant
      beneficial effects in favour of the treatment package and support the
      implementation of a behavioural approach in audiological rehabilitation research.

PMID- 7726807
TI  - Relapse rate and subsequent parental reaction after successful treatment of
      children suffering from nocturnal enuresis: a 2 1/2 year follow-up of
      bibliotherapy.
AB  - Results 2 1/2 years after an enuresis nocturna training are presented, including
      rate of success, percentage and duration of relapse for 113 children (mean age
      11.6 year at the start of the training). The bibliotherapeutic treatment by
      parents did not require any intervention by a professional. Behaviour of parents
      in the event of a relapse differed between training conditions. Children in the
      Arousal condition recovered faster from a relapse, 90% of their parents used the
      Arousal training again at relapse or did not intervene at all and none of them
      consulted a professional. Clearly they had confidence in the method of Arousal
      training: combining the alarm device with reinforcement for correct behaviour at
      the time the alarm goes off. Parents in control conditions did not use the alarm
      device as often as the parents in the Arousal condition, but tried other means
      with less success, including consulting professionals.

PMID- 7726808
TI  - Origins of childhood dental fear.
AB  - This study explored Rachman's theory of fear acquisition applied to fear of the
      dentist in a large sample of low income American primary school children.
      Children and their mother/guardians were interviewed or completed questionnaires
      in the home about fear acquisition and related concerns. A multivariate logistic
      regression model was evaluated in order to explore the relationship of direct
      conditioning and modeling variables to fear levels. Both direct conditioning and
      parent modeling factors were significant independent predictors of fear level
      even when controlling for gender, age and other sociodemographic and attitudinal
      factors.

PMID- 7726809
TI  - Self selection and sample selection in a treatment study of social phobia.
AB  - The external validity or generalizability of a treatment outcome study may be
      influenced by the choices patients make (self-selection) and by study
      requirements intended to increase internal validity or protect subject welfare
      (e.g. sample selection). Although these effects are well-known, they have rarely
      been studied, and little is known about the impact they may have on
      generalizability of findings. In this study, subjects accepting random assignment
      to a larger study examining pharmacologic and cognitive-behavioral treatments for
      social phobia were compared with subjects refusing random assignment (i.e. self
      selected) and excluded subjects (i.e. "sample-selected"). "Acceptors" differed
      from "refusers" on some measures suggesting that they have a lower annual income
      and may have fewer social supports. Therefore, they may have fewer available
      resources and might be more willing to accept help wherever it is offered.
      Despite these differences, acceptors differed from refusers on just one
      pretreatment measure of clinical functioning. Excluded subjects did not differ
      from refusers or acceptors on demographic or pretreatment clinical measures.
      Refusers and excluded subjects were treated with the same cognitive-behavioral
      treatment used in the comparative outcome study, and their posttreatment data
      were compared with the subgroup of acceptors who were randomly assigned to that
      treatment. Again, there were few significant differences. These results suggest
      that while self-selection and sample selection may have influenced some
      characteristics of the sample in this comparative outcome study, the three groups
      of subjects were clinically similar and responded similarly to cognitive
      behavioral treatment of social phobia.

PMID- 7726810
TI  - Psychometric characteristics of revised Sociotropy and Autonomy Scales in college
      students.
AB  - Beck, Epstein, Harrison and Emery (unpublished manuscript, 1983) developed the
      Sociotropy-Autonomy Scale (SAS) to assess personality constructs that were
      considered possible vulnerability factors to reactive depression. Principal
      components and factor analyses of an expanded 93-item version of the SAS were
      performed with successive samples of undergraduates totalling 2041 Ss. Only 59
      items were needed to establish the generalizabilities of one dimension of
      Sociotropy and two dimensions of Autonomy. Three subscales reflecting Sociotropy,
      Solitude and Independence were constructed from these items. The convergent and
      discriminant validities of the three subscales were assessed with respect to a
      variety of other psychological tests. The overall pattern of relationships
      indicated that Solitude was positively correlated with dysphoria, perfectionism,
      self-criticalness, and loneliness. In contrast, Independence was positively
      correlated with perfectionism and self-efficacy, but inversely related to concern
      about approval from others. Sociotropy was correlated with dependency, self
      criticalness, and affiliation motivation. The findings supported the construct
      validity of the three revised SAS subscales.

PMID- 7726811
TI  - The structure of negative emotional states: comparison of the Depression Anxiety
      Stress Scales (DASS) with the Beck Depression and Anxiety Inventories.
AB  - The psychometric properties of the Depression Anxiety Stress Scales (DASS) were
      evaluated in a normal sample of N = 717 who were also administered the Beck
      Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). The DASS was
      shown to possess satisfactory psychometric properties, and the factor structure
      was substantiated both by exploratory and confirmatory factor analysis. In
      comparison to the BDI and BAI, the DASS scales showed greater separation in
      factor loadings. The DASS Anxiety scale correlated 0.81 with the BAI, and the
      DASS Depression scale correlated 0.74 with the BDI. Factor analyses suggested
      that the BDI differs from the DASS Depression scale primarily in that the BDI
      includes items such as weight loss, insomnia, somatic preoccupation and
      irritability, which fail to discriminate between depression and other affective
      states. The factor structure of the combined BDI and BAI items was virtually
      identical to that reported by Beck for a sample of diagnosed depressed and
      anxious patients, supporting the view that these clinical states are more severe
      expressions of the same states that may be discerned in normals. Implications of
      the results for the conceptualisation of depression, anxiety and tension/stress
      are considered, and the utility of the DASS scales in discriminating between
      these constructs is discussed.

PMID- 7726812
TI  - The Beck Depression Inventory: testing and cross-validating a second-order
      factorial structure for Swedish nonclinical adolescents.
AB  - The intent of the present study was to test for the validity and equivalency of a
      second-order factorial structure of the Beck Depression Inventory for and across
      three independent samples (n1 = 661; n2 = 239; n3 = 196) of nonclinical Swedish
      adolescents. The model under study derived from a cross-validated study of
      Canadian high school adolescents. Model fitting, testing and equating were based
      on the analysis of covariance structures within the framework of a confirmatory
      factor analytic model. Of major importance was the tenability of the hypothesized
      model for Swedish adolescents. Only minor differences where found among samples,
      which involved correlated errors and one cross-loading (Sample 2). Results are
      expected to be of substantial interest to both researchers and clinicians whose
      concerns focus on depression as it bears on this population.

PMID- 7726813
TI  - Microscopic computation in human brain evolution.
AB  - When human psychological performance is viewed in terms of cognitive modules, our
      species displays remarkable differences in computational power. Algorithmically
      simple computations are generally difficult to perform, whereas optimal routing
      or "Traveling Salesman" Problems (TSP) of far greater complexity are solved on an
      everyday basis. It is argued that even "simple" instances of TSP are not purely
      Euclidian problems in human computations, but involve emotional, autonomic, and
      cognitive constraints. They therefore require a level of parallel processing not
      possible in a macroscopic system to complete the algorithm within a brief period
      of time. A microscopic neurobiological model emphasizing the computational power
      of excited atoms within the neuronal membrane is presented as an alternative to
      classical connectionist approaches. The evolution of the system is viewed in
      terms of specific natural selection pressures driving satisfying computations
      toward global optimization. The relationship of microscopic computation to the
      nature of consciousness is examined, and possible mathematical models as a basis
      for simulation studies are briefly discussed.

PMID- 7726814
TI  - Quality improvement in health care organizations: a general systems perspective.
AB  - A systems analysis of healthcare organizations demonstrates that methods for
      improving quality involve the effective feedback regulation of key organizational
      performance parameters. Information flow is impaired in dysfunctional healthcare
      organizations, which often disregard significant clinical problems while
      preferentially tracking nonclinical indicators and clinical data considered most
      likely to meet the organization's standards. Such organizations thus achieve
      "pseudocompliance" with external requirements, but do not systematically work to
      improve the quality of clinical care or their performance as organizations.
      Efforts by government agencies and national organizations to foster quality
      improvement activities have had limited success precisely because local
      organizations perceive these efforts as externally imposed. Leaders' anxieties
      about their own and their organizations' autonomy, control, and performance can
      cause unwillingness to review data indicating performance problems,
      oversimplification of decision criteria, and reluctance to formulate meaningful
      conclusions and act on them. Contemporary quality improvement models, such as
      Continuous Quality Improvement (CQI) and Total Quality Management (TQM),
      reconnect leaders to their organizations' quality processes by emphasizing the
      leaders' roles in promoting quality as an organizational value, setting
      meaningful quality goals, and actively u sing information to improve
      organizational effectiveness.

PMID- 7726815
TI  - Family interaction in the home. Development of a new coding system.
AB  - The Home Interaction Scoring System (HISS) is a recently developed observational
      coding system allowing for the systematic description of naturalistic family
      interaction. After discussing the importance of naturalistic observation
      procedures, we present a brief review of several coding systems that have been
      developed for this purpose. Based on our evaluation of the strengths and
      weaknesses of these systems, our rationale for developing a new system is
      presented, followed by a detailed discussion of the current status of the HISS.
      In a final section, we discuss a number of in-progress and planned analyses of
      the HISS relevant to the instrument's value in the assessment of family process.

PMID- 7726816
TI  - Determining the collateral effects of peer tutor training on a student with
      severe disabilities.
AB  - In one experiment and two case studies, we evaluated the impact of training peer
      tutors without disabilities to provide effective instructional procedures with a
      student with severe disabilities who exhibited aberrant behaviors in the
      classroom. Peer tutors received training on how to provide appropriate commands
      and specific praise statements, as well as to decrease negative statements. In
      the experiment, two peer tutors were taught these skills in a multiple baseline
      design. Two case studies further clarified the impact of the peer tutor training.
      In Case Study 1, one peer tutor received training on the three skills
      concurrently and data were assessed in an AB design. In Case Study 2, one peer
      tutor was trained prior to working with the student to determine if a peer tutor
      who had no prior history with the student could work effectively with minimal
      disruptions from the onset. Data were also measured on the student's aberrant
      behaviors and his compliance before, during, and after training the peer tutors.
      Results indicated that the peer tutors learned to provide appropriate commands
      and specific praise and to reduce negative statements. More important, as a
      collateral effect of the training program, the student's aberrant behaviors
      decreased and his compliance to requests improved.

PMID- 7726817
TI  - The effects of social skills instruction and parental involvement on the
      aggressive behaviors of African American males.
AB  - The purpose of this study was to investigate the effects of social skills
      instruction on identified acts of aggression. Five elementary-aged African
      American male students attending general education classes in an urban public
      school setting were taught social skills using modeling, role playing, corrective
      feedback, and differential reinforcement of alternative or incompatible
      behaviors. Parent training and parent notes were used for the maintenance and
      transfer of newly learned social skills. A multiple baseline design across
      students, combined with a withdrawal feature, was employed to assess the
      effectiveness of the social skills instruction. Data were collected in the
      classroom and cafeteria to assess generalization of the training to naturalistic
      settings. Results indicate the social skills instructional package to be
      functionally related to a decrease in aggressive behaviors with four of the five
      students and maintained by parental involvement.

PMID- 7726818
TI  - Differential effects of methylphenidate and self-reinforcement on attention
      deficit hyperactivity disorder.
AB  - Six boys aged 9 to 12 years attended a tutoring class focusing on reading for 30
      minutes each morning. The investigators employed a modified Latin-square design
      in which each child began with a 5-day baseline phase followed by six 10-day
      treatment phases that used drug placebo, noncontingent reinforcers, 0.3 mg/kg
      methylphenidate, 0.7 mg/kg methylphenidate, and self-reinforcement in various
      combinations. Amount of academic performance was the major measure of outcome and
      the target behavior of self-reinforcement. Drug placebo and noncontingent
      reinforcers had no systematic impact. Methylphenidate had differential effects
      across the recorded behaviors. Self-reinforcement improved the target behavior;
      the mean effect size for self-reinforcement was 2.66. The combined effects of
      methylphenidate and self-reinforcement on academic performance were greater than
      either of the treatments given alone (mean effect size = 2.89).

PMID- 7726819
TI  - A social skills training program for preschoolers with developmental delays.
      Generalization and social validity.
AB  - This investigation was designed to assess a social skills training program with
      32 developmentally delayed preschoolers. Subjects were evaluated in an
      unstructured play session, matched for levels of appropriate and inappropriate
      social behaviors, and assigned to either a treatment or control condition. The
      treatment group (N = 16) was presented with a 6-week protocol involving positive
      reinforcement, modeling, rehearsal, feedback, and time out. Controls (N = 16)
      received no instruction beyond regular classroom activities during the 6 weeks.
      The two groups were reevaluated in a posttest session and again in a
      generalization setting where two peers with developmental delays (not included in
      either experimental condition) were included. Prosocial behaviors were
      successfully taught and maintained in generalization settings. Efforts to reduce
      inappropriate behaviors were less successful. A test of social validity via
      teachers' ratings of videotapes of pretest and posttest assessments was also
      conducted. Implications for generalization and social validity research are
      discussed.

PMID- 7726820
TI  - Cognitive-behavioral treatment of obsessions.
AB  - Three patients with obsessive-compulsive disorder whose major complaints were
      obsessional thoughts with cognitive neutralization as opposed to overt rituals
      were treated with a cognitive-behavioral package. Cognitive neutralization
      involves both cognitive rituals and a variety of less ritualized coping
      strategies all designed to remove the thought and decrease discomfort. In a
      departure from earlier case studies, the patients were treated in a multiple
      baseline design across subjects. All three patients reported decreased discomfort
      and improved their professional and/or interpersonal functioning. Gains were
      maintained at follow-up (8 to 11 months).

PMID- 7726821
TI  - Proline accumulates in plants exposed to UV radiation and protects them against
      UV induced peroxidation.
AB  - Proline accumulated in the shoots of seedlings of rice (Oryza sativa), mustard
      (Brassica juncea) and mung bean (Vigna radiata) exposed to UV radiations. The
      level of proline in the seedlings increased significantly with increase in UV
      exposure time. The production of malondialdehyde (an indice of lipid
      peroxidation) was also higher in the shoots of seedlings exposed to UV radiation
      as compared to controls, suggesting that UV radiations promote lipid
      peroxidation. The extent of UV radiation promoted enhancement in the levels of
      proline as well as that of malondialdehyde was higher in the seedlings of rice
      than those of mung bean or mustard. This lead us to believe that UV radiation
      induced proline accumulation protects plants against UV radiation promoted
      peroxidative processes. UV radiations also promoted peroxidation in linolenic
      acid micelles. The presence of proline along with linolenic acid micelles during
      UV exposure caused a considerable reduction in the production of malondialdehyde.
      This study, for the first time shows that plants exposed to UV radiations
      accumulate proline and proline can protect plant cells against UV radiation
      induced peroxidative processes.

PMID- 7726822
TI  - Native and asialo-Tamm-Horsfall glycoproteins as important ligands for the
      detection of GalNAc beta 1-->and Gal beta 1-->4GlcNAc active lectins.
AB  - The binding properties of human Tamm-Horsfall Sd(a+) urinary glycoprotein(THGP)
      and asialo-THGP with various applied lectins was investigated by quantitative
      precipitin and precipitin inhibition assays. Both glycoproteins completely
      precipitated Abrus precatorius agglutinin(APA). They also reacted well with
      Wistaria floribunda (WFA), Glycine max (soybean, SBA), and Ricinus communis
      agglutinins and precipitated over 78% of the lectin nitrogen added, but reacted
      poorly or weakly with all alpha-anomeric GalNAc specific lectins, such as Helix
      pomatia (HPA), Phaseolus lunatus (lima bean, LBL), and Maclura pomifera (MPL)
      lectins. The glycoprotein-lectin interaction was inhibited by GalNAc beta 1-->,
      Gal beta 1-->4GlcNAc, or by both. The findings suggest that Sd (a+) THGP and
      asialo-THGP are among the best water-soluble glycoprotein ligands for GalNAc beta
      1-->and Gal beta 1-->4GlcNAc active lectins.

PMID- 7726823
TI  - Signals from the IL-1 receptor homolog, Toll, can activate an immune response in
      a Drosophila hemocyte cell line.
AB  - The Toll gene encodes an interleukin 1 receptor-like protein that mediates
      dorsoventral polarity in the Drosophila embryo. The possible involvement of Toll
      or Toll-like proteins also in the Drosophila immune response was investigated by
      overexpressing Toll10B, a constitutively active mutant protein, in the Drosophila
      blood cell line mbn-2. Induction of the Cecropin A1 (CecA1) gene, coding for a
      bactericidal peptide, was used as an indicator for the immune response. Toll10B
      was found to increase CecA1 transcription, as detected with a cotransfected CecA1
      lacZ reporter gene construct. This effect depends on the presence of a kappa B
      like site in the CecA1 promoter. The endogenous Toll gene is expressed in mbn-2
      cells, indicating that this gene may normally play a role in Drosophila blood
      cells.

PMID- 7726824
TI  - Biochemical and calmodulin binding properties of estrogen receptor binding
      cyclophilin expressed in Escherichia coli.
AB  - Bovine estrogen receptor binding cyclophilin (ERBC), a cyclophilin component of
      the unactivated estrogen receptor, has been efficiently expressed in Escherichia
      coli as a fusion with glutathione S-transferase (GST) and purified by single-step
      chromatography on glutathione-agarose. Thrombin cleavage from GST allowed the
      isolation of purified, recombinant ERBC. The fusion protein, GST-ERBC, and
      recombinant ERBC were both characterised for peptidyl prolyl cis-trans isomerase
      activity. With N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as substrate, GST-ERBC
      demonstrated a kcat/KM value of 5.1 x 10(5) M-1s-1 at 5 degrees C. The isomerase
      activity was inhibited by cyclosporin A with an IC50 value of 1030 nM. These
      values indicate that ERBC has a decreased catalytic efficiency and sensitivity to
      cyclosporin A relative to human cyclophilin. Retention of the GST-ERBC fusion
      protein on calmodulin-agarose in the presence of Ca2+ and subsequent elution with
      EGTA has provided evidence that ERBC is a calmodulin-binding protein.

PMID- 7726825
TI  - Interaction between caltropin and the C-terminal region of smooth muscle
      caldesmon.
AB  - Caltropin (CaT) binds caldesmon (CaD) in a Ca(2+)-dependent manner with an
      affinity higher than that of calmodulin (CaM). Photo-crosslinking between CaT and
      a benzophenone-labeled C-terminal CaD fragment (27K) results in a 35-kDa protein
      that corresponds to the 1:1 adduct between CaT and 27K. In the absence of Ca2+,
      no crosslinking is obtained. This result is similar to that obtained with CaM and
      27K. The apparent affinity of CaM for GS17C, a CaM-binding peptide of CaD, is
      weakened by CaT, suggesting CaT competes with CaM for the peptide. In contrast to
      CaM, CaT does not induce changes in the tryptophan fluorescence of GS17C. Thus
      although the two Ca(2+)-binding proteins behave similarly, there are differences
      in their interactions with CaD.

PMID- 7726826
TI  - Mutational study at Ser300 position of the Escherichia coli lactose repressor.
AB  - We have previously reported that a Ser300Asn mutant of the Escherichia coli
      lactose repressor protein produced a temperature-sensitive phenotype. In order to
      analyze the structure-function relationship of the lactose repressor protein, we
      conducted 18 amino acid substitutions at this Ser 300 site by using in vitro
      mutagenesis. The substitutions at this position that exhibited repressors with
      the wild-type phenotype in vivo were Gly, Ala, Ile, Thr, Met and Cys; the other
      10 substitutions examined (Leu, Val, Tyr, Trp, Asp, Glu, Gln, His, Lys and Arg)
      resulted in the lacI- phenotype. In addition, the Ser300Phe mutation resulted in
      the lacIts phenotype, while the Ser300Pro mutation resulted in lacIts,s. It seems
      likely that the Ser300 position plays an important role in oligomer formation and
      inducer binding.

PMID- 7726827
TI  - EGF-induced activation of 70-kDa S6 kinase in CHO cells expressing human EGF
      receptors.
AB  - We investigated epidermal growth factor (EGF)-induced activation of 85-kDa/110
      kDa phosphatidylinositol (PI)-3-kinase and 70-kDa S6 kinase in Chinese hamster
      ovary cells expressing the human EGF receptor. EGF-induced activation of p70 S6
      kinase was comparable to that induced by insulin, whereas that of PI-3-kinase in
      anti-phosphotyrosine immunoprecipitates was very small compared with insulin.
      Wortmannin, a p85/p110 PI-3-kinase inhibitor, inhibited EGF-induced activation of
      p70 S6 kinase in a dose-dependent manner. Given that several proteins homologous
      to catalytic subunit of p85/p110 PI-3-kinase have been identified and that
      wortmannin inhibits distinct form of PI-3-kinase, the present results suggest
      that wortmannin-sensitive kinases that resemble catalytic subunit of p85/p110 PI
      3-kinase may participate in the signaling pathway from EGF receptors to p70 S6
      kinase.

PMID- 7726828
TI  - Human peripheral eosinophils have a specific mechanism to express gp91-phox, the
      large subunit of cytochrome b558.
AB  - Eosinophils as well as neutrophils, monocytes and B lymphocytes are noted for
      lacking normal cytochrome b558 in patients with X-linked chronic granulomatous
      disease. The eosinophils of an X-linked male patient, however, fully expressed
      surface cytochrome b558, generated superoxide anion to a normal extent and
      definitely expressed the large subunit of cytochrome b558 (gp91-phox). His
      mononuclear leukocytes contained a diminished amount of gp91-phox mRNA with
      normal coding sequences. All the coding sequences and a putative poly (A) signal
      of his gp91-phox gene were normal. These results indicate that eosinophils have a
      specific mechanism to express gp91-phox and suggest that the mechanism lies at
      the transcriptional step of the gene.

PMID- 7726829
TI  - Amino acids of the third transmembrane domain of the AT1A angiotensin II receptor
      are involved in the differential recognition of peptide and nonpeptide ligands.
AB  - The differential role of amino acids of the third transmembrane domain on peptide
      and nonpeptide recognition by the AT1 angiotensin II receptor has been evidenced.
      The mutation of Ser105 into alanine completely abolished peptide agonist and
      antagonist binding, while the binding of nonpeptide ligands, including the
      original radioligands [3H] LF 7-0156 and [3H] LF 8-0129, was more moderately
      affected. Reverse pharmacological changes, i.e., unchanged affinities for peptide
      agonists or antagonists and drastically reduced affinities for nonpeptide
      antagonists, were observed upon alanine replacement of Asn111. These results
      confirm that the binding sites for peptide and nonpeptide molecules are not
      totally overlapping and delineate new amino acids as candidates for the selective
      receptor interaction with the two categories of ligands. Their integration in
      topographical studies is discussed.

PMID- 7726830
TI  - Influence of salt loading on the cardiac and renal preproendothelin-1 mRNA
      expression in stroke-prone spontaneously hypertensive rats.
AB  - Endothelin-1 is a potent vasoactive peptide which may play a role in the
      regulation of vascular resistance through its autocrine/paracrine effects. We
      have investigated the influence of salt loading on the renal and cardiac
      production of endothelin-1 in stroke prone spontaneously hypertensive rats, a
      classical model of hypertension. The results show that the dietary salt intake
      did not change systolic blood pressure nor the renal expression of the
      preproendothelin-1 mRNA but increased cardiac expression of the endothelin-1 gene
      transcript and a concomitant ventricular hypertrophy.

PMID- 7726831
TI  - Enzymatic synthesis and degradation of nicotinate adenine dinucleotide phosphate
      (NAADP), a Ca(2+)-releasing agonist, in rat tissues.
AB  - We have recently found that nicotinate adenine dinucleotide phosphate (NAADP) is
      a potent agonist that triggers Ca2+ release from intracellular stores of sea
      urchin eggs, and that its action is distinct from effects of IP3 and cyclic ADP
      ribose (J. Biol. Chem. 270:3216, 1995). Now we report that extracts from rat
      brain, heart, liver, and spleen but not kidney cortex contain enzymatic activity
      which catalyzes NAADP synthesis by exchange of nicotinamide for nicotinic acid
      and which is probably catalyzed by NAD(P)-glycohydrolase. Extracts from these
      tissues also inactivate NAADP in the rank inverse to their ability for NAADP
      synthesis. These results suggest that NAADP, a Ca(2+)-releasing agent, can be
      generated in mammalian tissues, namely in brain.

PMID- 7726832
TI  - Suppression of elastin gene expression in dermal fibroblasts by protein
      phosphatase inhibitor okadaic acid.
AB  - Treatment of human skin fibroblasts with okadaic acid, an inhibitor of
      serine/threonine specific protein phosphatases 1 and 2A, resulted in a marked
      reduction in elastin mRNA levels, with maximal inhibition of 80%. The inhibitory
      effect of okadaic acid on elastin mRNA levels was efficiently prevented by
      retinoic acid and cycloheximide and was further enhanced by phorbol ester
      treatment. Upregulation of elastin mRNA levels by transforming growth factor-beta
      2 was abrogated by simultaneous treatment of cells with okadaic acid. Okadaic
      acid had no effect on the expression of human elastin promoter/CAT chimeric gene
      in fibroblasts cultured from skin of transgenic mice. These results provide
      evidence that protein phosphatases 1 and 2A play an important role as positive
      regulators of elastin gene expression in dermal fibroblasts.

PMID- 7726833
TI  - Selection of glucocorticoid-resistant mutations from an AtT-20 cell line
      containing a glucocorticoid-regulated selectable transgene.
AB  - AtT-20/IDG8 cells contain the stably transfected, selectable gene, neomycin
      phosphotransferase, under negative glucocorticoid regulation. Thus, when cultured
      in the simultaneous presence of the neomycin analogue, G418, and dexamethasone,
      AtT-20/IDG8 cells fail to grow. Our hypothesis was that mutated AtT-20/IDG8 cells
      capable of growth in such medium would have a defect in the glucocorticoid
      mediated regulation of the neor gene. AtT-20/IDG8 cells were chemically
      mutagenized using ethyl-methane sulfonate and cloned in the presence of G418 and
      dexamethasone. Fourteen clones were obtained and loss of glucocorticoid control
      of neor expression was confirmed in them all. The naturally occurring gene, pro
      opiomelanocortin, which is down-regulated by glucocorticoids in parent AtT
      20/IDG8 cells, was down-regulated by dexamethasone in ten of the mutant lines,
      indicating that in those cells the receptor was functional in spite of aberrant
      regulation of neor. In the other four lines, pro-opiomelanocortin regulation was
      lost, also suggesting that a general transcription factor, such as the receptor,
      had been altered. These results indicate that multiple factors are involved in
      glucocorticoid-mediated gene regulation and that new, informative mutations can
      be produced after insertion of a regulated, selectable gene into a previously non
      selectable cell line.

PMID- 7726834
TI  - Expression of insulin-like growth factor receptor mRNA in rabbit atherosclerotic
      lesions.
AB  - We have found by 'in situ' hybridization a high level of expression of insulin-
      like growth factor I receptor (IGF-I R) gene in foam cells of atherosclerotic
      rabbit aortas. By reaction with either anti- rabbit macrophage (RAM11) or anti
      smooth muscle cell antibodies we also found that most cells expressing increased
      amounts of IGF-I R mRNA were of smooth muscle cell origin. Thus, increased IGF-I
      R mRNA levels might be related to the genesis of the atheroma plaque.

PMID- 7726835
TI  - Culture density and the activity, abundance and phosphorylation of the Na+/H+
      exchanger isoform 1 in human fibroblasts.
AB  - The Na+/H+ exchanger isoform 1 (NHE-1) is a ubiquitous membrane glycoprotein
      present on most eukaryotic cells. Its activity, abundance and phosphorylation are
      regulated by a variety of growth factors and agonists. Although cell contact and
      inhibition of proliferation may reduce its activity, little is known of the
      influence of cell culture density on these measurements. The effect of culture
      density on the intracellular pH (pHi) and activity of NHE-1 of human MRC5
      fibroblasts was thus investigated using fluorometry with BCECF, NHE-1 abundance
      with western blotting and NHE-1 phosphorylation using specific polyclonal
      antibodies. Proliferating cells in low density cultures had lower pHi and NHE-1
      activity (per litre of cell water) than contact inhibited confluent cultures.
      Such cells in low density cultures were larger than those in very confluent
      cultures. NHE-1 activity per cell and NHE-1 protein abundance also showed an
      increasing trend with culture density. However, the turnover number of NHE-1
      remained at around 3000 s-1 in low density and sub-confluent cultures, only
      decreasing in very confluent cultures. Moreover, NHE-1 phosphorylation declined
      with increased culture density. Cell culture density has profound effects on NHE
      1 activity, abundance and turnover number, with associated changes in NHE-1
      phosphorylation.

PMID- 7726836
TI  - A cell division inhibitor SulA of Escherichia coli directly interacts with FtsZ
      through GTP hydrolysis.
AB  - E. coli SulA is an SOS-inducible protein that inhibits cell division. FtsZ is a
      protein that plays a central role in bacterial cell division. Using purified SulA
      protein that was fused to the maltose binding protein, we demonstrate in vitro
      that SulA interacts with FtsZ to form a stable complex. The reaction requires GTP
      and Mg ion. GDP and GTP gamma S cannot substitute for GTP, which suggests that
      hydrolysis of GTP is required for the reaction. The complex is formed in a molar
      ratio of approximately one to one of the two proteins. It is likely that the
      complex formation represents the in vivo mechanism by which SulA inhibits cell
      division.

PMID- 7726837
TI  - Antibody against human alpha 1 beta 1 integrin inhibits HeLa cell adhesion to
      laminin and to type I, IV, and V collagens.
AB  - In HeLa cells beta 1 integrin forms heterodimers with alpha 1, alpha 2, alpha 3,
      alpha 5 and alpha 6 integrin subunits. Integrin alpha v beta 5 can also be
      detected. A monoclonal antibody SR-84 identified the alpha 1 integrin subunit in
      immunoprecipitation assays and inhibited alpha 1-related cell adhesion to
      different matrix proteins, laminin-1 and type I, IV, and V collagens, whereas its
      effect on adhesion to type II collagen was marginal. HeLa cells do not attach to
      type VI collagen. The presence of magnesium was essential for HeLa cell adhesion,
      whereas calcium alone was not sufficient and high concentrations of calcium even
      counteracted the effect of magnesium. Cell adhesion to type I collagen was
      sensitive to changes in pH, unlike cell adhesion to type IV collagen. We conclude
      that SR-84 is a valuable tool to study alpha 1 integrin-related functions, and
      that in HeLa cells alpha 1 beta 1 integrin is a magnesium-dependent receptor for
      type I, IV, and V collagens but not for type II and VI collagens.

PMID- 7726838
TI  - Protein tyrosine kinases expressed in glomeruli and cultured glomerular cells:
      Flt-1 and VEGF expression in renal mesangial cells.
AB  - Protein tyrosine kinases play an important role in cellular proliferation and
      differentiation of various cell types. To identify potential tyrosine kinases
      involved in glomerular functions we have utilized the polymerase chain reaction
      (PCR) and degenerate oligonucleotides for isolation of such genes from isolated
      glomeruli, cultured mesangial cell, and glomerular endothelial cells. Sequence
      analysis of PCR-amplified cDNAs resulted in the isolation of 24 tyrosine kinases.
      Here we describe for the first time the constitutive expression of 15 tyrosine
      kinases, tyro-1, tyro-4, tyro-6, hyk, Ptk-3, Ryk, tie, yes, lyn, tec, Jak1, Jak2,
      Jak3, c-abl, and flk, in renal glomeruli. In addition, Flt-1, an endothelial cell
      specific receptor for vascular endothelial growth factor (VEGF), is expressed in
      renal mesangial cells and its gene expression is up-regulated upon the
      stimulation of platelet-derived growth factor (PDGF) with the concomitant up
      regulation of VEGF. These data suggest that possible involvement of VEGF/Flt-1
      system in cytokine-induced mesangial cell proliferations.

PMID- 7726839
TI  - Identification of a putative antioxidant response element in the 5'-flanking
      region of the human gamma-glutamylcysteine synthetase heavy subunit gene.
AB  - We have cloned the human gamma-glutamylcysteine synthetase heavy subunit gene
      (GCSh) from a P1 library and isolated a 5.5kb fragment (P1-GCS5') from the 5'-end
      of the P1 clone. P1-GCS5' has been sequenced from -1460 to +547. Multiple
      transcription start sites were identified by primer extension and S1 nuclease
      protection. Two start sites were identified by primer extension analysis within
      23 bp (+1 and +10) of a consensus TATAAAA box; all sequences were numbered
      relative to the 5'-most of these two sites. Two additional major start sites were
      identified at -106 and +398. This latter site was the most prominent of all the
      initiation sites. In addition to a TATA box, the promoter contains a CCAAT box at
      -125 and GC boxes up- and down-stream of the TATAAAA. In addition, the first few
      hundred base pairs of the sequence are highly GC-rich (approximately 75%). This
      sequence also contains several Sp-1 binding sites, a consensus AP-1 site and
      several AP-1-like binding sites, as well as putative AP-2 sites. A consensus
      metal responsive element (MRE) was identified at position +198. Sequence analysis
      also identified a putative core (5'-TGACnnnGCA-3') antioxidant response element
      (ARE) at -862 to -853. As is typical of other AREs, a second AP-1-like sequence
      is located adjacent to the core sequence. These results suggest that GCSh gene
      expression in response to oxidative challenge may be regulated through an
      antioxidant response element similar to those recently detected in the promoter
      region of several Phase II enzymes.

PMID- 7726840
TI  - Insulin-dependent phosphatidylinositol 3'-kinase activity co-precipitates with
      insulin receptor in human circulating mononuclear cells.
AB  - In order to establish a working cellular model for the study of post-receptor
      signaling events, insulin-dependent phosphatidylinositol 3' (PtdIns 3')-kinase
      activity was investigated in circulating mononuclear cells from normal subjects.
      The p85 alpha regulatory subunit of PtdIns 3'-kinase co-precipitated with
      activated insulin receptor as revealed by immunoblotting. Whereas insulin
      receptor substrate-1 was weakly detected, insulin increased 5.5 +/- 1.5-fold
      (mean +/- SD) PtdIns 3'-kinase activity in receptor immunoprecipitates. We
      conclude that insulin-stimulated PtdIns 3'-kinase activity is measurable in
      circulating mononuclear cells which may constitute an easily available cellular
      model for the detection of post-receptor defects in insulin-resistant states.

PMID- 7726841
TI  - GLY113-->ASP can restore activity to the ASP51-->SER mutant in the melibiose
      carrier of Escherichia coli.
AB  - ASP51 in the putative membrane-spanning helix 2 of the melibiose carrier of
      Escherichia coli was replaced by SER. This mutation caused failure of the cell to
      transport melibiose and failure to ferment melibiose on indicator plates. A
      melibiose-positive revertant was isolated from these plates and was found to have
      two additional mutations, GLY113-->ASP (in helix 4) and PHE16-->LEU (in helix 1).
      The double mutant ASP51-->SER/GLY113-->ASP was constructed and showed
      accumulation of melibiose. On the other hand ASP51-->SER/PHE16-->LEU showed no
      activity. It is concluded that the new carboxyl group at position 113 compensates
      for the loss of the carboxyl group at position 51.

PMID- 7726842
TI  - Suppression of in vitro invasion of human fibrosarcoma cells by a leupeptin
      analogue inhibiting the urokinase-plasmin system.
AB  - A leupeptin analogue, pyroglutamyl-Leu-Arg-CHO (Pyr-Leu-Arg-CHO), is an inhibitor
      of urokinase and plasmin, while leupeptin inhibits only plasmin. Pyr-Leu-Arg-CHO
      was shown to inhibit in vitro invasion of human fibrosarcoma HT1080 cells
      reducing cellular collagenase activity. Pyr-Leu-Arg-CHO suppressed the invasion
      of the cells in a Boyden chamber assay with an IC50 of 12 micrograms/ml. Addition
      of plasminogen to HT1080 cells increased the type IV collagenase activity, and
      Pyr-Leu-Arg-CHO inhibited this activation of the collagenase with an IC50 of 3
      micrograms/ml. Leupeptin inhibited both the invasion and collagenase activation
      at higher concentrations than that of Pyr-Leu-Arg-CHO. The gelatin zymography of
      the conditioned medium revealed that a new gelatinolytic band, possibly an
      activated form of MMP-2, appeared by the addition of plasminogen. The activation
      of MMP-2 was also inhibited strongly by Pyr-Leu-Arg-CHO. These results indicate
      that Pyr-Leu-Arg-CHO suppresses the in vitro invasion by preventing the
      activation of type IV collagenase through inhibition of the urokinase-plasmin
      system.

PMID- 7726843
TI  - Expression and inflammatory regulation of haptoglobin gene in adipocytes.
AB  - Haptoglobin (HP) is the major hemoglobin binding protein which is synthesized
      mainly in the liver. It functions to prevent iron loss and kidney damage in human
      and other mammals. Recently, HP has been shown to possess antioxidant and
      angiogenic properties. As one of the major acute phase reactants, HP's levels in
      plasma increase significantly during inflammation, infection and malignancy. In
      this study, high levels of HP mRNA were found to be transcribed by adipocytes in
      addition to liver cells in mice. After inflammation had been induced in vivo,
      expression of the haptoglobin gene rose six-fold in adipose tissue, an increase
      compatible with that observed in the normal mouse liver. The expression of HP by
      adipocytes presents new directions in which HP's role as an antioxidant or as an
      angiogenic factor can be investigated.

PMID- 7726844
TI  - DNA binding and transcriptional properties of wild-type and mutant forms of the
      homeodomain protein Msx2.
AB  - Msx2 is a mammalian homeodomain protein that is expressed during craniofacial
      development. A proline-to-histidine substitution at residue 148 of human Msx2
      results in an autosomal dominant form of craniosynostosis. In this study, both
      wild-type and mutant Msx2 were shown to specifically bind to a DNA sequence
      previously identified as a high-affinity binding site for the related homeodomain
      protein Msx1. In co-transfection assays both wild-type and mutant Msx2 repressed
      reporter gene transcription in a dose-dependent but binding-site-independent
      manner. These results provide evidence that Msx2 is a transcriptional repressor
      and suggest that the mutant form of Msx2 may exert its pathophysiologic effects
      on craniofacial development by a gain-of-function mechanism.

PMID- 7726845
TI  - Morphological and biochemical changes in a hematopoietic cell line induced by
      jacalin, a lectin derived from Artocarpus integrifolia.
AB  - Treatment of the human erythroleukemia cell line K562 with the galactose-binding
      lectin, jacalin, results in rapid and profound alterations in the morphology and
      biochemistry of the cells. Within minutes of lectin addition, the cells adhere to
      the plastic tissue culture surface, and within hours, the cells spread on the
      surface, acquiring a monocyte-like appearance. Jacalin treatment results in
      elevated expression of CD61 (integrin beta 3) and CD14, a monocyte-associated
      cell surface antigen. These results suggest that jacalin treatment of K562 cells
      triggers intracellular events that result in differentiation along the monocyte
      lineage.

PMID- 7726846
TI  - A mitogen-activated protein kinase independent pathway involved in the
      phosphorylation and activation of cytosolic phospholipase A2 in human neutrophils
      stimulated with tumor necrosis factor-alpha.
AB  - Although tumor necrosis factor (TNF)-alpha stimulation of human neutrophils does
      not result in a significant release of arachidonic acid, it primes the cell for
      arachidonic acid release when cells are further stimulated by agents that induce
      an intracellular calcium increase. We demonstrate that TNF-alpha stimulation of
      neutrophils induces the phosphorylation of cytosolic phospholipase A2 (cPLA2) and
      also increases its activity. These results indicate that although TNF-alpha, by
      itself, does not cause the release of arachidonic acid in intact cells, it
      increases the phosphorylation and activation of the enzyme cPLA2. Since we
      recently found that TNF-alpha stimulation of neutrophils does not increase the
      tyrosine phosphorylation or activation of the p42erk2 and p44erk1 mitogen
      activated protein kinases (MAPKs), the present studies demonstrate the
      involvement of a MAPK independent pathway in the phosphorylation and activation
      of cPLA2.

PMID- 7726848
TI  - ATP bimodal switch that regulates the ligand binding and signal transduction
      activities of the atrial natriuretic factor receptor guanylate cyclase.
AB  - Atrial natriuretic factor (ANF)-dependent guanylate cyclase (ANF-RGC) is a single
      chain transmembrane-spanning protein, containing both ANF binding and catalytic
      cyclase activity. ANF binding to the extracellular receptor domain activates the
      cytosolic catalytic domain, generating the second messenger cyclic GMP.
      Obligatory in this activation process is an intervening step regulated by the ATP
      binding to the cyclase. This is a signal transduction step that bridges the
      events of ligand binding and cyclase activation. A defined structural motif
      (Gly503-Xa-Gly505-Xa-Xa-Xa-Gly509), termed ATP regulatory module (ARM), is
      critical for this step. The present study shows that the ARM-Gly505 residue acts
      as an ATP bimodal switch in regulating both the ligand binding and signal
      transduction activities of ANF-RGC, thus representing a critical site to turn the
      hormone signal on and off.

PMID- 7726847
TI  - Gonadal steroids modulate interleukin-1 receptor antagonist mRNA expression in
      cultured human monocytes.
AB  - This study investigated whether gonadal steroids modulate the expression of the
      cytokine Interleukin-1 receptor antagonist in monocytes. Human male peripheral
      monocytes were isolated and cultured in serum free media with serially diluted
      concentrations of estradiol and progesterone. mRNA expressions with increasing
      steroid concentrations were compared by reverse transcription-polymerase chain
      reaction for intracellular and secretory interleukin-1 receptor antagonist
      specific primers and glyceraldehyde 3-phosphate dehydrogenase primers. Monocyte
      expression of secretory Interleukin-1 receptor antagonist mRNA was significantly
      elevated in the presence of normal physiological levels of estradiol (10(-11) M)
      and progesterone (10(-8) M), while expression was suppressed by higher
      concentrations of steroids. Intracellular receptor antagonist was also detected.
      This study is the first to describe the dose related response of cytokine
      interleukin-1 receptor antagonist to gonadal steroids.

PMID- 7726849
TI  - Glycosylation-dependent binding of pancreatic type I phospholipase A2 to its
      specific receptor.
AB  - Pancreatic group I phospholipase A2 (PLA2-I) elicits various biological responses
      via its specific receptor. The PLA2-I binding to its recombinant soluble receptor
      was considerably reduced after Peptide: N-glycosidase F treatment of the
      receptor. In cultured bovine smooth muscle cells, treatment with tunicamycin, a N
      glycosylation inhibitor, resulted in a decrease in the number of PLA2-I receptor.
      In addition, the PLA2-I binding was blocked by the addition of a lectin, Wheat
      germ agglutinin. These results suggest an involvement of N-linked
      oligosaccharides of the PLA2-I receptor for its ligand recognition.

PMID- 7726850
TI  - Focal adhesion kinase is not essential for in vitro and in vivo differentiation
      of ES cells.
AB  - Focal adhesion kinase, FAK, is a unique protein tyrosine kinase found in cellular
      focal adhesions. It is widely expressed and highly phosphorylated during
      embryogenesis. To examine the function of FAK in cell differentiation, we made
      FAK-deficient embryonic stem (ES) cells by homologous recombination. However, FAK
      deficiency did not interfere with differentiation of the ES cells into cells of
      three germ layers when implanted subcutaneously into nude mice or when treated
      with retinoic acid in vitro, nor was there any evidence of defects in
      hematopoiesis in vitro.

PMID- 7726851
TI  - The unfolded-protein-response element discriminates misfolding induced by
      different mutant pro-sequences of yeast carboxypeptidase Y.
AB  - The C-terminal region of the chaperone-like pro-sequence (py) of yeast
      carboxypeptidase Y (CPY) is suggested to be crucial for the folding of mature
      CPY. In order to study the influence of hydrophobic residues in this domain, a
      set of mutations have been introduced in py. Unexpectedly, only small amounts of
      CPY precursors are expressed when Leu108, at the C-terminal end of py, is
      substituted for polar residues Lys, Arg or Asp. In contrast, substitution with
      hydrophobic residues Val, Ile or Ala permit normal expression. Interestingly, the
      poorly expressed molecules are coreglycosylated, implying that they have failed
      to leave the endoplasmic reticulum (ER). The ER-retained molecules caused an
      induction in the levels of BiP, signifying that polar substitutions at position
      108 of pre-py-CPY induce misfolding. Quite surprisingly, a reporter gene, linked
      to concatamerized unfolded-protein-response elements, reveals that py-mediated
      misfolding of CPY is not really identical in all mutants. This shows that a
      simple transcriptional assay can assess the subtleties of pro-sequence mediated
      protein folding in an eukaryotic cell.

PMID- 7726852
TI  - Zn2+ binding to cardiac calsequestrin.
AB  - Zn2+ binding to canine cardiac calsequestrin was investigated using the Zn2+
      specific fluorescence dye salicylcarbohydrazone (SACH), 65Zn2+ overlay and Zn(2+)
      IDA chromatography. Cardiac calsequestrin binds approximately 200 moles of
      Zn2+/mole of protein with the Kd = 300 microM. Zn2+ binding to calsequestrin was
      further confirmed by 65Zn2+ overlay and Zn(2+)-dependent aggregation of the
      protein. However, calsequestrin did not bind to a Zn(2+)-IDA-agarose column,
      indicating that histidine residues may not be involved in Zn2+ binding to the
      protein. Circular dichroism revealed only minor Zn(2+)-dependent conformational
      changes in calsequestrin. We conclude that calsequestrin is a Ca(2+)- and Zn(2+)
      binding protein and that Zn2+ may modulate the structure and function of the
      protein.

PMID- 7726853
TI  - The Saccharomyces cerevisiae processing alpha 1,2-mannosidase is an inverting
      glycosidase.
AB  - The alpha 1,2-mannosidase from Saccharomyces cerevisiae, which removes one
      specific alpha 1,2-linked mannose residue from Man9GlcNAc2, is a member of the
      Class 1 alpha 1,2-mannosidase family conserved from yeast to mammals. Although
      Class 1 alpha 1,2-mannosidases are essential for the maturation of N-linked
      oligosaccharides in mammalian cells, nothing is known about their mechanism of
      action. The availability of sufficient quantities of recombinant yeast alpha 1,2
      mannosidase and its homology with the mammalian enzymes make it a good model to
      study the catalytic mechanism of this family of alpha 1,2-mannosidases. The
      stereochemical course of hydrolysis of Man9GlcNAc by the yeast enzyme was
      followed by proton nuclear magnetic resonance spectroscopy. It was observed that
      beta-D-mannose is related from the oligosaccharide substrate, thereby
      demonstrating that the enzyme is of the inverting type.

PMID- 7726854
TI  - Drosophila glutathione S-transferase D27: functional analysis of two consecutive
      tyrosines near the N-terminus.
AB  - The Drosophila glutathione S-transferase D27 (GST D27) has been purified and
      characterized after direct expression of the intronless gstD27 gene in E. coli.
      The GST D27 has both conjugation activity against the common substrate 1-chloro
      2,4-dinitrobenzene and peroxidase activity against cumene hydroperoxide. Its pH
      optimum is 8.5 in 0.125 M bis-tris propane buffer at 22 degrees C. It is more
      thermal labile than the human GST121. The GST D27 has two tyrosines at positions
      3 and 4. Both of them appear to be important but neither of them is essential for
      the enzyme activity. Thus, other residues may also participate in catalysis. The
      two tyrosines of GST D27 could also be important in binding to GSH or S-hexyl
      GSH. Results from in vitro biochemical analyses were confirmed by the in vivo
      activity-based CDNB growth inhibition analyses. Our results clearly indicate that
      the Drosophila GST D isozymes are different from any of the known mammalian GSTs.

PMID- 7726855
TI  - Requirement for phosphoinositide 3-kinase in insulin-stimulated GLUT4
      translocation in 3T3-L1 adipocytes.
AB  - Insulin stimulates glucose transport in muscle and fat cells by inducing the
      redistribution of a specific glucose transporter, GLUT4, from intracellular
      vesicles to the cell surface. Phosphoinositide (PI) 3-kinase has been implicated
      as a key intermediate in insulin-stimulated glucose transport by studies that
      have examined the effects of wortmannin and LY294002, which are thought to be
      specific inhibitors of this enzyme. However, the specificity of these compounds
      for PI 3-kinase has recently been questioned. Epidermal growth factor, which
      activates mitogen-activated protein kinase in mouse 3T3-L1 adipocytes, has now
      been shown to have no effect on PI 3-kinase activity or GLUT4 translocation in
      these cells. Furthermore, microinjection of a dominant negative mutant of the 85
      kDa subunit of PI 3-kinase, which lacks a binding site for the catalytic 110-kDa
      subunit, inhibited GLUT4 translocation induced by insulin in 3T3-L1 adipocytes;
      microinjection of the wild-type protein had no effect. These observations
      indicate that PI 3-kinase is necessary for insulin-induced GLUT4 translocation
      and glucose transport in adipocytes.

PMID- 7726856
TI  - Failure of copper incorporation into ceruloplasmin in the Golgi apparatus of LEC
      rat hepatocytes.
AB  - Copper incorporation into ceruloplasmin during ceruloplasmin synthesis was
      studied by comparing LEC and control rats. Major 132 and 136 kDa ceruloplasmins
      were found in microsomes and the Golgi apparatus, respectively, isolated from
      liver homogenates of LEC and control rats. Copper analysis showed that no copper
      was detected in the ceruloplasmin in the microsomes of either rat. Copper was
      present in ceruloplasmin in the Golgi apparatus and serum of controls, while it
      was not detected in ceruloplasmin in the Golgi apparatus and serum of the LEC
      rat. These results indicate that copper is incorporated into ceruloplasmin in the
      Golgi apparatus of normal hepatocytes. LEC rats fail to incorporate copper into
      ceruloplasmin in the Golgi apparatus.

PMID- 7726857
TI  - Phosphorylation of tyrosine residues of RNA polymerase II and other nuclear
      proteins by active chromatin tyrosine kinase(s).
AB  - We demonstrate here for the first time that protein tyrosine kinases are present
      in the active chromatin of nucleus. The presence of tyrosine kinase activity in
      the active chromatin was initially determined using poly (Glu,Na-Tyr;4:1) (PGT)
      as a tyrosine phosphorylatable substrate. Active chromatin in the presence of
      cofactors phosphorylated PGT at a rate of 40 pmol/min. The phosphorylation of PGT
      by active chromatin was inhibited by 41, 47 and approximately 95% with genistein,
      n-ethylmaleimide and quercetin (known inhibitors of tyrosine kinases),
      respectively. A Lineweaver-Burk plot revealed an apparent Km of 50 micrograms/ml
      and Vmax of 45 pmol/min for active chromatin tyrosine kinase(s). Analyses of
      phosphorylation of endogenous substrates by immunoprecipitation, western blotting
      and phosphoamino acids revealed that active chromatin protein tyrosine kinase(s)
      are able to phosphorylate tyrosine residues of the large subunit of RNA pol II
      and several other active chromatin proteins. The ability of AC-PTKs to
      phosphorylate many proteins of active chromatin components argues strongly for
      its role(s) in regulating transcription.

PMID- 7726858
TI  - Characterization of the apolipoprotein(a) gene.
AB  - Five homologous genes have been isolated and characterized and found to belong to
      the plasminogen-apolipoprotein(a) gene family. One of these genes is the true
      apolipoprotein(a) gene because it has typical regulatory elements and exons
      coding for kringle 4 repeats. Nucleotide sequence analysis revealed that each of
      11 types of the kringle 4 repeats is encoded by two exons and that the splice
      junctions of the exons coding for the (pseudo)serine protease domain of apo(a)
      were also located in exactly the same positions as those of plasminogen.

PMID- 7726859
TI  - Detection of polymorphisms in the 5'-flanking region of the gene for
      apolipoprotein(a).
AB  - Concentration of lipoprotein(a) in plasma is inherited in an autosomal co
      dominant manner and its high concentration leads to atherothrombotic disease.
      Nucleotide sequence analysis of the apolipoprotein(a) gene revealed the presence
      of polymorphisms in its 5'-flanking region, which can be analyzed by in vitro
      amplification employing gene-specific primers. Genomic DNAs from normal
      individuals have been subclassified into four alleles according to the patterns
      of restriction digestion. The ratios of these subtypes differed between
      Caucasians and Japanese and in patients with myocardial infarction. It is very
      likely that the 5'-alleles in part control the plasma lipoprotein(a) level.

PMID- 7726860
TI  - Multi-strand binding of nuclear factors to a repressor of mouse mammary tumor
      virus transcription can be distinguished kinetically.
AB  - NRE1 is a DNA sequence element in the long terminal repeat of mouse mammary tumor
      virus that represses viral transcription in mature T cells. In addition to double
      stranded binding activity, factors in Jurkat T cell nuclear extracts bind
      specifically to each of the two single-strands of NRE1. Here we show that binding
      to the three forms of NRE1 can be distinguished kinetically. The on rates for
      double, upper and lower-strand NRE1 binding were 1.5, 3, and 11 min,
      respectively. Binding was extremely stable with off-rates varying from 30 and 60
      min for double and upper-strand binding to 12 h for lower-strand binding. In
      addition, a truncated form of NRE1 that is only bound as a double-strand was
      observed to have an on rate of binding of 4 min and an off rate of 4 h.

PMID- 7726861
TI  - cDNA cloning of murine Nrf 2 gene, coding for a p45 NF-E2 related transcription
      factor.
AB  - A lambda gt11 cDNA library was constructed from poly-A rich RNA prepared from
      circulating murine yolk sac derived nucleated erythroblasts, on day 9 of
      gestation. In addition to the embryonic globin genes, this library was found to
      contain clones for the hematopoietic specific p45 NF-E2, as well as p18 NF-E2 and
      p45 NF-E2 related factor 1 (Nrf 1) genes. Using a degenerate oligonucleotide
      17mer probe coding for a part of the highly conserved DNA binding domain for p45
      NF-E2, we have isolated murine Nrf 2, a second murine homologue related to p45 NF
      E2. The murine Nrf 2 gene is expressed not only in erythroid cells, but also in
      the 3T3 murine fibroblast cell line.

PMID- 7726862
TI  - Intact alpha-subunit is required for membrane-binding of human mitochondrial
      trifunctional beta-oxidation protein, but is not necessary for conferring 3
      ketoacyl-CoA thiolase activity to the beta-subunit.
AB  - We have studied the activities of alpha and beta subunit enzymes of the beta
      oxidation trifunctional protein complex in a patient who does not process the
      alpha-subunit. Long-chain 3-ketoacyl-CoA thiolase, the beta-subunit enzyme, was
      transported into the mitochondrial matrix, where it expressed normal levels of
      activity, but was not translocated to the membrane. Thus, intact alpha-subunit is
      required for trifunctional protein membrane translocation, but is not necessary
      for conferring activity of the beta-subunit.

PMID- 7726863
TI  - Relationship between free iron level and rat liver mitochondrial dysfunction in
      experimental dietary iron overload.
AB  - The concentration of total iron in the hepatic tissue and mitochondria from rats
      fed a 2.5% carbonyl iron supplemented diet progressively increased up to 40 days,
      then reached nearly a steady-state. By contrast the level of free iron
      (desferrioxamine-chelatable) exhibited a transient but significant increase at 40
      days of treatment, only in this period of treatment the induction of lipid
      peroxidation and the resulting mitochondrial abnormalities in calcium transport
      was observed too. The enhancement of the energy dissipating mitochondrial calcium
      cycling was found to be associated with a significant decrease of endogenous
      mitochondrial ATP content. As to the pathophysiological mechanism for
      hepatocellular injury in iron overload, these results indicated that the transit
      pool of free iron may play a critical role in initiating organelle dysfunctions,
      at least in this experimental model of iron overload.

PMID- 7726864
TI  - Inhibition of mitochondrial respiration by a para-quinone methide.
AB  - A relatively stable para quinone methide was prepared from 4-allyl-2,6
      dimethoxyphenol. In aqueous solution the quinone methide had a half-life of 52
      min, yet reacted rapidly with thiols such as glutathione or cysteine. The unusual
      stability of this quinone methide allowed us to directly test its effects on
      mitochondrial respiration. The quinone methide was a potent inhibitor of
      succinate-dependent mitochondrial respiration (IC50 = 47 microM). The inhibition
      appeared to be due to the depletion of protein thiols, since its effects were
      comparable to 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB, Ellman's reagent). This
      quinone methide may prove a useful tool in the investigation of the specific
      effects of quinone methides on cells which lead to cytotoxicity.

PMID- 7726865
TI  - Identification of a phorbol ester responsive region in the myeloid-specific
      promoter of the c-fgr proto-oncogene.
AB  - Expression of the c-fgr proto-oncogene is activated during differentiation of
      myeloid cells. We used a luciferase reporter assay to identify sequences that
      regulate c-fgr gene transcription during differentiation of human U937
      promonocytic cells, induced by phorbol 12-myristate 13-acetate (PMA) or by tumour
      necrosis factor-alpha (TNF-alpha) and 1,25-dihydroxycholecalciferol (1,25-DHCC).
      We found that the region from nucleotides -344 to -116, with respect to the
      transcriptional start site, is required for basal activity of the c-fgr promoter
      in U937 cells, and that the region from nucleotides -1211 to -752 is responsive
      to PMA. No sequence elements responsive to TNF-alpha and 1,25-DHCC were found,
      suggesting that these agents induce c-fgr mRNA accumulation by a mechanism
      differing from that mediating the effects of PMA.

PMID- 7726866
TI  - Retinoid agonist activities of synthetic geranyl geranoic acid derivatives.
AB  - Micromolar concentrations of 4,5- didehydro geranyl geranoic acid (GGA) were able
      to induce up-regulation of retinoic acid receptor-beta gene expression in human
      hepatoma-derived cell line, HuH-7, to the same extent as all-trans RA. In
      chloramphenicol acetyl transferase (CAT) assay with retinoic acid response
      element-beta, GGA and 4,5-didehydro GGA were both positive, but 2,3-dihydro GGA
      was negative, even though these GGA derivatives have been reported to be all
      potent ligands for cellular retinoic-acid-binding protein(CRABP). However,
      10,11,14,15- tetrahydro- 4,5- didehydro GGA, a compound without any affinity for
      CRABP, transactivated CAT gene expression. On the other hand, only GGA and 4,5
      didehydro GGA were active to induce CAT gene expression through retinoid X
      response element of cellular retinol binding protein, type II gene. We show for
      the first time that chemically synthesized acyclic organic acids are potential
      agonists of natural retinoids.

PMID- 7726867
TI  - Identification of the ETA receptor subtype that mediates endothelin induced
      autocrine proliferation of normal human keratinocytes.
AB  - Endothelin-1 has a wide range of pharmacological effects in various tissues and
      acts as autocrine/paracrine factor. The potential of ET-1 to function as an
      autocrine growth factor was evaluated in normal human keratinocytes. Radioligand
      binding studies showed that 125I-ET-1 bound to a single class of high-affinity
      binding sites on the surface of the cells. The dissociation constant was 0.045 nM
      with receptor numbers of 1700 sites/cell. Treatment with serum caused increases
      in expression of binding sites (3500 sites/cell), with no change in binding
      affinity. ET-1 stimulated thymidine incorporation in these cells that expressed
      ET receptors. An ET antagonist selective for the ETA receptor subtype (BQ 123)
      inhibited DNA synthesis stimulated by ET-1 and reduced the basal growth rate of
      unstimulated cells. These data suggest that the ET-1 induced DNA synthesis is
      mediated by ETA receptor subtype and that endogenously produced ET-1 promotes the
      autocrine proliferation of keratinocytes.

PMID- 7726868
TI  - Interleukin-10 decreases tyrosine phosphorylation of discrete lipopolysaccharide
      induced phosphoproteins in human granulocytes.
AB  - Although Interleukin-10 (IL-10) has been recently shown to modulate
      lipopolysaccharide (LPS)-induced release of cytokines in human granulocytes, the
      intracellular signalling pathways of LPS have been only partially defined, while
      those of IL-10 remain unknown. The present study shows that LPS induces an
      increase in tyrosine phosphorylation of a discrete number of proteins, in a time-
      and concentration-dependent manner. In addition, IL-10 negatively influenced
      protein tyrosine phosphorylation in LPS-treated human polymorphonuclear
      leukocytes (PMN). The effect of IL-10 was evident only after 60 min LPS
      stimulation and was detected by analysing either cell lysates or lysates which
      were previously immunoprecipitated with anti-phosphotyrosine antibodies. Amongst
      the tyrosine phosphoproteins mostly affected by IL-10 in LPS-stimulated cells
      were the species with molecular weights ranging from 46 to 49 kDa. The identity
      and possible function of these proteins remain unknown. Taken together, our
      results suggest that tyrosine phosphorylation may constitute one of the
      intracellular events that mediate LPS and IL-10 responses in granulocytes.

PMID- 7726869
TI  - Abundant expression of GLUT1 and GLUT3 in rat embryo during the early
      organogenesis period.
AB  - The developmental change of both GLUT1 and GLUT3 protein in rat embryonal and
      fetal brain was examined using Western blot analysis and immunohistochemistry.
      The brains were collected from fetuses (gestational days 10 to 20), newborn, and
      adult rats. On day 10, the levels of GLUT1 and GLUT3 expressions were twofold
      higher than those of adult levels, but thereafter decreased rapidly as the
      gestation progressed. The tissue distribution of GLUT1 and GLUT3 in embryo was
      apparently distinct. On day 10, GLUT1 was expressed in the neural tube, gut,
      heart and optic vesicle, while GLUT3 was expressed in the surface ectoderm and
      gut. Thus, high affinity glucose transporters may be required in the early
      organogenesis period because their energy requirement is completely dependent
      upon anaerobic glycolysis. GLUT3 may facilitate glucose transfer from amniotic
      fluid to the embryo and GLUT1 may supply glucose for use as an embryonal fuel.

PMID- 7726870
TI  - [Antiganglioside antibodies and neuropathies].

PMID- 7726871
TI  - Scleroderma following silicone implantation: a cumulative experience of 11 cases.
AB  - In the 3 years since the initial report of 5 patients who developed scleroderma
      in association with silicone breast implants, 6 additional silicone implant
      recipients have presented with scleroderma. Two of these patients received
      silicone chin implants. A total of 5 patients elected to remove their prostheses.
      Two patients have had marked improvement of cutaneous scleroderma. The other 3
      patients, however, died secondary to progressive visceral involvement. This
      cumulative experience of 11 cases of scleroderma following silicone implantation
      suggests additional evidence of an association between the 2. Careful case
      control studies over an extended period of time are required to determine the
      incidence of this outcome.

PMID- 7726872
TI  - Co-existence of Capgras and deClerambault's syndromes.

PMID- 7726873
TI  - Performances of family practice diplomates on successive mandatory
      recertification examinations.
AB  - BACKGROUND: In 1969 the American Board of Family Practice (ABFP) became the 19th
      medical specialty board and the first since the inception of medical specialty
      certification to mandate recertification. As of July 1993, 16 other boards have
      adopted time-limited certification, but only two have reached the first
      recertification of their diplomates. As recertification approaches for the 14
      boards, each will be faced with decisions concerning process, examination content
      and scope, and standards for passing. The physicians who will be facing mandatory
      recertification must be adequately prepared or accept the consequences of losing
      their certification. METHOD: This study examined the performances of six cohorts
      of family physicians--three cohorts of 711 practice-qualified physicians
      certified in 1971, 1972, and 1973, and three cohorts of 1,233 residency-trained
      physicians certified in 1977, 1978, and 1979--who were successfully recertified
      on successive six-year cycles from 1977 through 1991. Analyses of variance,
      multiple regression analysis, and Pearson correlation coefficients were used to
      investigate the relationships among the composite scores on the various
      certification and recertification examinations and among examination composite
      scores and demographic variables. RESULTS: There were significant (p < .01)
      declines in performance on each recertification examination. The residency
      trained physicians had higher examination scores than did the practice-qualified
      physicians. Multiple regression analysis showed the last recertification score to
      be the strongest predictor of the next recertification score. The combination of
      previous scores and demographic variables resulted in the ability to predict
      between 63% and 74% of the variance in the most current recertification composite
      score. CONCLUSION: The results raise questions for further investigation, and
      such investigation may affect specialty boards' design of and/or examinees' test
      taking strategies on future recertification examinations. For example, the
      decline in examination performance from certification through successive
      recertifications may result from factors related to the practice of medicine. It
      is possible that as the practice life of a family physician evolves, the focus of
      the practice becomes narrower, and this narrowed focus results in a decline in
      performance on an examination, half of which covers the breadth of the specialty.
      Thus, the medical specialties addressing mandatory recertification may wish to
      give thorough consideration to the focus of the examination--scope of specialty
      or scope of the practice, or some combination of both--as well as the
      implications of the standard-setting process used for recertification.

PMID- 7726874
TI  - The tenth plague--death of the "newborn"?

PMID- 7726875
TI  - Disappearing CT lesion in a nonepileptic patient.
AB  - Despite its high incidence, the exact cause of disappearing CT lesions in
      patients with epilepsy is not clear. We document a non-epileptic patient, whose
      clinical picture simulated idiopathic intracranial hypertension, but CT showed a
      spontaneously resolving ring enhancing lesion.

PMID- 7726876
TI  - Comparison of Hemochron and HemoTec activated coagulation time target values
      during percutaneous transluminal coronary angioplasty.
AB  - OBJECTIVES: The aim of this study was to determine whether activated coagulation
      time measurements from Hemochron and HemoTec machines can be used interchangeably
      and whether similar activated coagulation time target ranges for adequate
      anticoagulation can be applied to both machines. BACKGROUND: Adequate
      anticoagulation is necessary for the safe performance of intravascular
      interventions such as percutaneous transluminal coronary angioplasty. In current
      practice, anticoagulation status is frequently assessed by way of the activated
      coagulation time with one of two commercially available systems, HemoTec and
      Hemochron. Each one employs a different technique to determine the time of clot
      formation; however, the same target activated coagulation time values for
      adequate anticoagulation have been used interchangeably in published studies.
      METHODS: A total of 311 paired samples were compared in 113 high risk patients
      undergoing angioplasty enrolled in a randomized trial of a platelet glycoprotein
      IIb/IIIa receptor antibody. Simultaneous activated coagulation time measurements
      were obtained before and after administration of heparin, and the difference
      between the values of both machines was calculated. The relation between the
      Hemochron and HemoTec values was determined by using linear regression analysis.
      All activated coagulation time measurements were classified as either therapeutic
      or subtherapeutic using an arbitrary activated coagulation time target of 300 s.
      RESULTS: There was a correlation between values from the two machines (r = 0.86),
      but the Hemochron values were consistently higher than the HemoTec values by a
      mean value +/- SD of 28 +/- 29%, with wide individual variation. After heparin
      administration, there was a significant (p < 0.0001) difference between the
      number of measurements classified as therapeutic by HemoTec (53%) and by
      Hemochron (94%). CONCLUSIONS: HemoTec and Hemochron activated coagulation time
      measurements cannot be used interchangeably. Appropriate target activated
      coagulation time ranges to determine adequate anticoagulation during coronary
      angioplasty need to be established for both machines; the target range for one
      machine should not be extrapolated to the other.

PMID- 7726877
TI  - Reflections on radiotherapy in Vietnam: political lessons still to be learned.
AB  - Radiotherapy in Vietnam represents a stark contrast to the level of care
      available in the United States. The issue of efficient administration of cancer
      care with available resources is common to both nations. The challenge for each
      country is to develop treatment strategies and political policies for effective
      and accessible care within budgetary constraints. Results of therapy, defined as
      the restoration of function, must be the measure of efficacy and efficiency. This
      demands a balance between control of tumor-related symptoms and treatment-related
      morbidity. The most inefficient use of resources is an ineffective treatment that
      results in complications, as we observed in Vietnam. As health care policies
      continue to develop in the United States, we must not fail to focus upon
      therapeutic outcome as the single most important parameter for measuring success
      relative to the personal and public investment in medicine.

PMID- 7726878
TI  - The association of mast cells and atherosclerosis: a morphologic study of early
      atherosclerotic lesions in young people.
AB  - Mast cell products, such as histamine, may contribute to the initiation and
      progression of the atherosclerotic plaque. To determine the relationship that may
      exist between early atherosclerotic plaques and mast cells we studied the aortas
      and coronary arteries of 115 young subjects aged 15 to 34 years who had traumatic
      deaths. Lesions were classified as normal intima, fatty streaks, fibro-fatty
      plaques, and fibrous plaques. Aortic and coronary artery segments with raised
      lesions had significantly greater numbers of mast cells in the adventitia (and
      occasionally intima and outer media) compared with those with a normal intima. In
      the aortic segments greater numbers of mast cells were located in the dorsal
      portion (lesion "prone") compared with the ventral half (lesion "resistant") (P <
      .05). These data support the concept that increased numbers of mast cells are
      associated with atherosclerosis and suggest a role for mast cell products in the
      evolution of the atherosclerotic plaque.

PMID- 7726879
TI  - Rationale drug therapy: reasons for failure and suggestions for its
      implementation.

PMID- 7726880
TI  - Are wall thickening measurements reproducible?
AB  - An early transesophageal echocardiography (TEE) study reported that there was
      high inter- and intraobserver variability in measurements of wall thickening
      (WT). This study reevaluated TEE for the measurement of WT in the transverse
      plane and, for the first time, evaluated it in the longitudinal plane. Ten
      patients were studied with a biplane TEE probe inserted and positioned to obtain
      a transverse short-axis (SA) view of the left ventricle at the midpapillary
      muscle level. A longitudinal transgastric long-axis (LA) view of the left
      ventricle was then obtained. This measurement sequence was performed four times
      in each patient. Off-line analysis was performed independently by two observers.
      In each tomographic cut of the ventricle, four locations for measurement were
      defined. WT was measured in three consecutive beats, and the results averaged
      (WT1). The observers repeated the measurements (WT2) 2 wk later, and the intra-
      and interobserver differences (mm) were calculated. Average differences for the
      intraobserver comparisons of wall thickening were small (0.08-0.24 mm), but the
      high standard deviations (1.17-2.44 mm) suggest significant variability between
      individual measurements. Thus it appears that measurements of wall thickening
      with small mean intraobserver bias may be possible, but to offset the potential
      for variability, multiple measurements are necessary. Also, careful
      standardization of location and edge definition is important to limit
      interobserver variability.

PMID- 7726881
TI  - The hippocratic oath: an anachronism?

PMID- 7726882
TI  - Dorsal and circumferential sheath reconstructions for flexor sheath defect with
      concomitant bony injury.
AB  - Dorsal and circumferential flexor sheaths were reconstructed by autogenous sheath
      graft in flexor tendon repair in 28 white leghorn chickens. The effect of the
      sheath reconstructions was evaluated by use of an experimental model of tendon
      transection associated with bony injury, superficial tendon excision, and 3 weeks
      of immobilization. Six weeks after reconstruction, the gliding excursion was
      assessed and adhesion formation, tendon healing, and survival of the grafted
      sheath were evaluated both macroscopically and histologically. Dorsal and
      circumferential sheath grafts resulted in tendon gliding that was significantly
      better than the group with sheath defect not reconstructed. The adhesion
      formation was apparently less severe, and tendon healing was better in the groups
      with sheath reconstruction than in the group without reconstruction. The group
      with dorsal sheath reconstruction did not differ significantly from that with
      circumferential reconstruction in gliding excursion and adhesion formation. This
      study demonstrates that separation of the injured tendons from the bony surface
      by autogenous sheath grafts may be beneficial to tendon gliding and for reducing
      adhesion formation.

PMID- 7726883
TI  - "Mini-congestive splenomegaly".

PMID- 7726884
TI  - Rheumatic heart disease.

PMID- 7726885
TI  - Regression analyses: what to report.

PMID- 7726886
TI  - Epithelioid angiosarcoma of the gallbladder.

PMID- 7726887
TI  - Unplanned extubation. Predictors of successful termination of mechanical
      ventilatory support.
AB  - BACKGROUND: Unplanned extubation (self-extubation or accidental extubation)
      occurs commonly in mechanically ventilated patients, and many patients do not
      receive mechanical ventilation indefinitely. Unfortunately, weaning parameters
      are often unavailable in the setting of unplanned extubation, and it would be
      useful to define pre-extubation respiratory and ventilatory parameters that
      predict which patients require reintubation. METHODS: The medical records of all
      patients who experienced unplanned extubation for the 2-year period of July 1989
      to July 1991 were reviewed. Pre-extubation values of respiratory rate, tidal
      volume (VT), fraction of inspired oxygen (FIo2), PEEP, ventilatory mode, and
      ventilator-delivered minute volume (VVE, ventilator rate multiplied by set VT)
      were recorded. In addition, the following data were obtained: age, gender,
      respiratory failure diagnosis, duration of intubation, amount, and type of
      sedative agents in the 24 h before extubation. Comparisons of these values among
      patients who ultimately required reintubation and those who were not reintubated
      were made using the Mann-Whitney U two-sample test. RESULTS: During this period,
      there were 23 unplanned extubations involving 22 patients. Reintubation was
      required for 18 episodes of unplanned extubation, but was not required for 5
      episodes. There were no significant differences between the two groups for any of
      the parameters except VVE and FIo2. The mean pre-extubation FIo2 of the
      reintubated group (0.49) was significantly higher than that of the patients who
      were not reintubated (0.35) (p = 0.021); all of the patients who remained
      extubated were receiving an FIo2 < or = 0.40. The VVE was also higher in the
      reintubated group (9.73 L/min) than in the patients who were not reintubated
      (1.40 L/min); all patients who remained extubated were receiving < or = 7.0 L/min
      of ventilator-delivered minute ventilation. CONCLUSIONS: Reintubation after
      unplanned extubation should not be considered mandatory. Patients who require
      reintubation have significantly higher preextubation FIo2 and ventilatory
      requirements than patients who remain extubated.

PMID- 7726888
TI  - Genetic conservation within subtypes in the hepatitis B virus pre-S2 region.
AB  - The antigenic determinants for the main hepatitis B virus (HBV) subtypes adw,
      adr, ayw and ayr lie in the S (surface) polypeptide. Two amino acid residues in
      particular, encoded by the S gene at codon positions 122 and 160, have been
      postulated to determine the different antigenic subtypes. In contrast, the 165
      nucleotide pre-S2 gene encodes an immunodominant region common to all subtypes
      that can give rise to neutralizing antibodies. We have characterized the pre-S2
      gene sequences of 29 HBV strains of the three main subtypes, adw, ayw and adr.
      Seven base positions showed variation that was entirely subtype-specific, with
      six of these variations leading to subtype-specific amino acid differences. This
      finding affords the possibility of using pre-S2 sequences for genetic subtyping.
      Two ayw strains from unrelated patients infected in the Middle East had identical
      pre-S2 sequences with a block of 12 nucleotides deleted. A geographical
      correlation with subtype observed from serological results was also apparent from
      phylogenetic analysis of DNA identities within the pre-S2 region. The results
      support the concept that the main HBV subtypes truly represent families of
      phylogenetically different strains.

PMID- 7726889
TI  - Pollen-related allergy in the European Mediterranean area.

PMID- 7726890
TI  - Discontinuing an implantable cardioverter defibrillator as a life-sustaining
      treatment.

PMID- 7726891
TI  - The long-term effects of the lipid-lowering agent fenofibrate in hyperlipidemic
      heart transplant recipients.

PMID- 7726892
TI  - Drug treatment of hypertension in the elderly: a meta-analysis.
AB  - PURPOSE: A meta-analysis of the effect of antihypertensive drug treatment on
      mortality and morbidity in elderly patients. DATA SOURCES: A literature search of
      published articles from January 1980 to February 1992. STUDY SELECTION:
      Randomized controlled trials of drug treatment of hypertension with end points
      for elderly patients reported separately. DATA EXTRACTION: Mortality or morbidity
      end points or both in patients older than 59 years were pooled by determination
      of typical odds ratio. A meta-regression was used to study heterogeneity.
      RESULTS: Nine major trials with 15,559 patients older than 59 years were
      identified. Death rates in the control group varied between 2.7% and 77.2%;
      stroke and coronary mortality increased with the severity-of-illness rank (P <
      0.001). Overall, treated patients had an approximately 12% reduction in all-cause
      mortality (odds ratio, 0.88; 95% CI, 0.80 to 0.97; 953 events compared with 1069
      events, P = 0.009). There was a 36% reduction in stroke mortality (odds ratio,
      0.64; CI, 0.49 to 0.82; 94 events compared with 149 events, P < 0.001) and a 25%
      reduction in coronary heart disease mortality (odds ratio, 0.75; CI, 0.64 to
      0.88; 263 events compared with 350 events, P < 0.001). Coronary morbidity was
      reduced 15% (odds ratio, 0.85; CI, 0.73 to 0.99; 325 events compared with 379
      events, P = 0.036), and stroke morbidity was reduced 35% (odds ratio, 0.65; CI,
      0.55 to 0.76; 247 events compared with 382 events, P < 0.001). CONCLUSION:
      Overall, treatment of hypertension in elderly patients produces a significant
      benefit in total mortality and cardiovascular morbidity and mortality. However,
      this benefit may be reduced in the oldest age groups.

PMID- 7726893
TI  - Intrapartum cardiotocography and the expert witness.
AB  - Fetal heart rate changes occur in the majority of labours and correlate poorly
      with perinatal outcome and subsequent neurological development. Obstetricians
      giving expert evidence related to the interpretation of intrapartum
      cardiotocographs are advised to exercise caution when expressing their opinions.

PMID- 7726894
TI  - A critical appraisal of the quality of quality-of-life measurements.
AB  - OBJECTIVE: To evaluate how well quality of life is being measured in the medical
      literature and to offer a new approach to the measurement. DATA SOURCES: Original
      English-language articles having the term "quality of life" in their titles were
      identified from a recent Quality-of-Life Bibliography and from two MEDLINE
      searches. Articles were eligible for review only if they described or used one or
      more "quality-of-life" instruments. STUDY SELECTION: Twenty-five articles were
      randomly selected from each of the three data sources. DATA EXTRACTION: Each
      article was reviewed for its compliance with two sets of criteria having several
      components, which are cited under "Data Synthesis." DATA SYNTHESIS: (1)
      Investigators conceptually defined quality of life in only 11 (15%) of the 75
      articles; identified the targeted domains in only 35 (47%); gave reasons for
      selecting the chosen quality-of-life instruments in only 27 (36%); and aggregated
      their results into a composite quality-of-life score in only 27 (38%) of 71
      eligible articles. (2) No article distinguished "overall" quality of life from
      health-related quality of life; patients were invited to give their own separate
      rating for quality of life in only 13 articles (17%); and among 71 eligible
      articles, patients were asked to supplement the stipulated items with personal
      responses in only nine (13%) and to rate the importance of individual items in
      only six (8.5%). CONCLUSIONS: Because quality of life is a uniquely personal
      perception, denoting the way that individual patients feel about their health
      status and/or nonmedical aspects of their lives, most measurements of quality of
      life in the medical literature seem to aim at the wrong target. Quality of life
      can be suitably measured only by determining the opinions of patients and by
      supplementing (or replacing) the instruments developed by "experts."

PMID- 7726895
TI  - Catheter-associated bacteremia with Nocardia nova with secondary pulmonary
      involvement.

PMID- 7726896
TI  - Pneumatosis cystoides intestinalis: an incidental finding in a patient with AIDS
      and cryptosporidial diarrhea.

PMID- 7726897
TI  - Side effects of dental materials.

PMID- 7726898
TI  - Studies with MHC-deficient knock-out mice reveal impact of both MHC I- and MHC II
      dependent T cell responses on Listeria monocytogenes infection.
AB  - Mutant mice with a defined genetic defect in the beta 2-microglobulin (beta 2m)
      or the H2-I-A beta chain, which are virtually devoid of functional CD8 or CD4
      alpha beta T cells, respectively, were employed for analyzing immune mechanisms
      involved in acquired resistance against Listeria monocytogenes. Although the
      lethal dose of L. monocytogenes was markedly lower for either mouse mutant as
      compared with their heterozygous control littermates, both beta m -/- and A beta 
      /- mutants were able to resolve low dose infection. However, in both mouse
      mutants, the course of disease was exacerbated and clearance was markedly
      delayed. Vaccine induced immunity against a secondary high dose infection lethal
      for naive animals was also impaired in beta 2m -/- and A beta -/- mice. However,
      both mutant mice were still capable of controlling secondary infection. Based on
      numbers of L. monocytogenes organisms in spleens, beta 2m -/- mutants suffered
      more dramatically from primary and secondary infection than A beta -/- mice. Ag
      induced IFN-gamma secretion was impaired during the early phase of infection in
      beta 2m -/- mice and at later stages in A beta -/- mice. Modulation of gamma
      delta T cells by mAb treatment led to significant increase in bacterial load of
      spleens in both beta 2m -/- and A beta -/- mice. Finally, the development of
      granulomatous lesions was markedly affected in both mutants. In beta 2m -/-
      mutants, infiltrative lesions appeared and in A beta -/- mice few inflammatory
      islets with necrotic centers developed. These data demonstrate the importance of
      both MHC I- and MHC II-dependent immune mechanisms in acquired resistance to L.
      monocytogenes and point to the necessity of a coordinated interaction between CD8
      and CD4 alpha beta T cells (and probably gamma delta T cells) in anti-L.
      monocytogenes resistance.

PMID- 7726899
TI  - Coronary angioplasty compared with bypass grafting.

PMID- 7726900
TI  - Generation and characterization of an ordered lambda clone array for the 460-kb
      region surrounding the murine Xist sequence.
AB  - The Xist sequence has several characteristics that make it a potential candidate
      for the X-inactivation center. To investigate the role of Xist and adjacent
      sequences lying within the X-inactivation center candidate region, a 460-kb
      region surrounding the murine Xist sequence has been arrayed in lambda contigs
      with a combination of IRS-PCR-based hybridization and YAC fragmentation. The
      orientation of the Xist sequence in relation to the telomere and centromere of
      the X Chromosome (Chr) has been established with this contig and shown to be
      inverted compared to that in human.

PMID- 7726901
TI  - In the pipeline: a wave of valuable medical technology.
AB  - Technologic change has proceeded at a rapid pace during the past twenty years,
      and advances that are even more remarkable are in sight over the next decade.
      These changes will be driven largely by advances in molecular and cell biology,
      imaging techniques, and tissue engineering. Therapies directed toward causes
      rather than consequences of disease could conceivably produce inexpensive cures
      and thus slow the rise in medical costs. A more likely scenario envisions a
      continued rise in costs as advances in technology produce many expensive
      interventions that extend life but are not curative.

PMID- 7726902
TI  - Tuberculosis: update and guidelines for management.

PMID- 7726903
TI  - Insulin dependent diabetes mellitus: a lethal disease in the developing world.

PMID- 7726904
TI  - Prescribing exercise in general practice. Encourage active community life.

PMID- 7726905
TI  - Is travel prophylaxis worth while? Economic appraisal of prophylactic measures
      against malaria, hepatitis A, and typhoid in travellers.
AB  - OBJECTIVES: To estimate the costs and benefits of prophylaxis against travel
      acquired malaria, typhoid fever, and hepatitis A in United Kingdom residents
      during 1991. DESIGN: Retrospective analysis of national epidemiological and
      economic data. MAIN OUTCOME MEASURES: Incidence of travel associated infections
      in susceptible United Kingdom residents per visit; costs of prophylaxis provision
      from historical data; benefits to the health sector, community, and individuals
      in terms of avoided morbidity and mortality based on hospital and community costs
      of disease. RESULTS: The high incidence of imported malaria (0.70%) and the low
      costs of providing chemoprophylaxis resulted in a cost-benefit ratio of 0.19 for
      chloroquine and proguanil and 0.57 for a regimen containing mefloquine. Hepatitis
      A infection occurred in 0.05% of visits and the cost of prophylaxis invariably
      exceeded the benefits for immunoglobulin (cost-benefit ratio 5.8) and inactivated
      hepatitis A vaccine (cost-benefit ratio 15.8). Similarly, low incidence of
      typhoid (0.02%) and its high cost gave whole cell killed, polysaccharide Vi, and
      oral Ty 21a typhoid vaccines cost-benefit ratios of 18.1, 18.0, and 22.0
      respectively. CONCLUSIONS: Fewer than one third of travellers receive vaccines
      but the total cost of providing typhoid and hepatitis A prophylaxis of 25.8m
      pounds is significantly higher than the treatment costs to the NHS (1.03m pounds)
      of cases avoided by prophylaxis. Neither hepatitis A prophylaxis nor typhoid
      prophylaxis is cost effective, but costs of treating malaria greatly exceed costs
      of chemoprophylaxis, which is therefore highly cost effective.

PMID- 7726906
TI  - The future of purchasing.

PMID- 7726907
TI  - Epidemic of asthma possibly associated with electrical storms.

PMID- 7726908
TI  - Time for a dental board checkup.

PMID- 7726909
TI  - Plastic surgery needs more training programs--not less!

PMID- 7726910
TI  - Taxonomic descriptions of eight new non-sterol-requiring mollicutes assigned to
      the genus Mesoplasma.
AB  - Twenty mollicute strains isolated primarily from insect hosts were characterized
      and arranged into eight new species in the genus Mesoplasma. Morphological
      examination of the organisms by electron and dark-field microscopic techniques
      revealed that the cells of each strain were small, nonhelical, nonmotile,
      pleomorphic, and coccoid and that each cell was surrounded by a single
      cytoplasmic membrane with no evidence of a cell wall. Although the new mollicutes
      grew well in media containing horse or fetal bovine serum, growth in serum-free
      or cholesterol-free medium occurred only when the medium contained 0.04%
      polyoxyethylene sorbitan (Tween 80). The optimum temperature for growth was
      usually 30 degrees C, but multiplication generally occurred over a temperature
      range of 10 to 32 degrees C. All strains catabolized glucose. Most strains did
      not hydrolyze arginine or urea, although three related strains isolated from
      fireflies (the strain PUPA-2T [T = type strain] group) did hydrolyze arginine.
      The genome sizes ranged from 825 to 930 kbp, and the DNA base compositions
      (guanine-plus-cytosine contents) ranged from 26.5 to 31.6 mol%. The proposed type
      strains of the eight new species were not serologically related to the type
      strains of four other Mesoplasma species, five Entomoplasma species, 11
      Acholeplasma species, and 100 Mycoplasma species and subspecies. Strain PS-1 (=
      ATCC 49582) is the type strain of Mesoplasma pleciae sp. nov., strain PUPA-2 (=
      ATCC 49581) is the type strain of Mesoplasma photuris sp. nov., strain YJS (=
      ATCC 51578) [corrected] is the type strain of Mesoplasma syrphidae sp. nov.,
      strain CHPA-2 (= ATCC 49578) is the type strain of Mesoplasma chauliocola sp.
      nov., strain ELCA-2 (= ATCC 49579) is the type strain of Mesoplasma corruscae sp.
      nov., strain GRUA-1 (= ATCC 49580) is the type strain of Mesoplasma grammopterae
      sp. nov., strain BARC 779 (= ATCC 49583) is the type strain of Mesoplasma
      coleopterae sp. nov., and strain BARC 857 (= ATCC 49584) is the type strain of
      Mesoplasma tabanidae sp. nov.

PMID- 7726911
TI  - RFLVs in mottled dappled alleles.

PMID- 7726912
TI  - Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in
      pancreatic adenocarcinoma.
AB  - The MTS1 gene on chromosome 9p21 encodes the p16 inhibitor of cyclinD/Cdk-4
      complexes, and is deleted or mutated in a variety of tumour types. We found
      allelic deletions of 9p21-p22 in 85% of pancreatic adenocarcinomas. Analysis of
      MTS1 in pancreatic carcinomas (27 xenografts and 10 cell lines) showed homozygous
      deletions in 15 (41%) and sequence changes in 14 (38%). These included eight
      point mutations (four nonsense, two missense and two splice site mutations) and
      six deletions/insertions, all accompanied by loss of the wild-type allele.
      Sequencing of MTS1 from primary tumours confirmed the mutations. Coexistent
      inactivations of both MTS1 and p53 was common and suggests that abnormal
      regulation of cyclin-dependent kinases may play an important role in the biology
      of pancreatic carcinoma.

PMID- 7726913
TI  - Chronic dizziness: an integrated approach.

PMID- 7726914
TI  - Clinical tutor and contract monitoring: a candle in the wind.

PMID- 7726915
TI  - Secrecy in the NHS.

PMID- 7726916
TI  - The association of mast cells and atherosclerosis.

PMID- 7726917
TI  - Driving, glaucoma, and the law. Patients need more information.

PMID- 7726918
TI  - Childhood antecedents of schizophrenia. Conclusions not supported by data.

PMID- 7726919
TI  - Treatment of myocardial infarction.

PMID- 7726920
TI  - Myths in medicine. Jenner did not discover vaccination.

PMID- 7726921
TI  - Incidence of coronary artery disease in asymptomatic uncomplicated essential
      hypertensive patients--evaluation by treadmill exercise test.
AB  - Treadmill exercise test was performed in 100 patients, 50 were hypertensive who
      were not having any clinical or electrocardiographic manifestation of coronary
      artery disease and 50 were controls. The test was positive in 28% of hypertensive
      patients as compared to 6% in controls. This study therefore suggests that
      hypertension is frequently associated with asymptomatic coronary artery disease
      as compared to normotension and it is concluded that exercise electrocardiography
      test is a definite diagnostic tool in diagnosis of coronary artery disease not
      only in symptomatic but also in asymptomatic patients with one or more risk
      factors.

PMID- 7726922
TI  - Computed tomography for single seizures.

PMID- 7726923
TI  - Secrecy in the NHS. NHS chief executive wants a culture of openness.

PMID- 7726924
TI  - Secrecy in the NHS. Creeping censorship occurs.

PMID- 7726925
TI  - Measles campaign. Involve general practitioners in future.

PMID- 7726926
TI  - Measles campaign. Parental awareness was high.

PMID- 7726927
TI  - The perils of povidone-iodine use re-examined.

PMID- 7726928
TI  - Comparison of the supraclavicular lateral paravascular and axillary approaches-
      comments.

PMID- 7726929
TI  - Antichlamydial antimicrobial therapy for asthma.

PMID- 7726930
TI  - Prenatal stress and fetal brain development.

PMID- 7726931
TI  - Comments on "Radiotherapy for nasopharyngeal carcinoma: shielding the pituitary
      may improve therapeutic ratio".

PMID- 7726932
TI  - Actual versus ideal treatment time in radiotherapy for head and neck cancer:
      catching up with the gaps.

PMID- 7726933
TI  - Who bears the costs of antidepressant in Australia?

PMID- 7726934
TI  - Chronic otitis externa due to Demodex canis in a Tibetan spaniel.

PMID- 7726935
TI  - Running and the development of disability with age.

PMID- 7726936
TI  - Dipyridamole and dobutamine for myocardial perfusion imaging.

PMID- 7726937
TI  - Can anyone take the pressure off?

PMID- 7726938
TI  - The NHS's winds of change.

PMID- 7726939
TI  - Prognosis after acute myocardial infarction.

PMID- 7726940
TI  - Improved use of a minisnare and guide wire for removal of a large-bore
      endoprosthesis.

PMID- 7726941
TI  - Error in estimates of size.

PMID- 7726942
TI  - Bifid pancreas.

PMID- 7726943
TI  - Environmental factors and bipolar disorder.

PMID- 7726944
TI  - Periodic paralysis secondary to gastrointestinal potassium loss.

PMID- 7726945
TI  - Is license exam a failure?

PMID- 7726946
TI  - Re: Spontaneous regression of metastases in a case of bilateral renal cell
      carcinoma.

PMID- 7726947
TI  - Core services and cardiac surgery.

PMID- 7726948
TI  - Vulvar intraepithelial neoplasia III: a clinical study of the outcome in 113
      cases with relation to the later development of invasive vulvar carcinoma.

PMID- 7726949
TI  - Collagenous spherulosis and collagenous crystalloids.

PMID- 7726950
TI  - It's time to cease fire.

PMID- 7726951
TI  - Cholesterol and violent behavior.

PMID- 7726952
TI  - Education about autopsies.

PMID- 7726953
TI  - Communicable diseases in child care centres: effects on parental work
      absenteeism.

PMID- 7726954
TI  - The sight test fee. Effectiveness of treatment for glaucoma remains unproved.

PMID- 7726955
TI  - Serum screening for Down's syndrome. Private patients may receive less
      counselling.

PMID- 7726956
TI  - Environmental lead and children's intelligence. Hair lead studies were excluded.

PMID- 7726957
TI  - Measles campaign.

PMID- 7726958
TI  - Immunising infants at risk of hepatitis B. BCG vaccination programmes may provide
      useful guidance.

PMID- 7726959
TI  - Reporting of air pollution levels.

PMID- 7726960
TI  - Cognitive-behavioural therapy for schizophrenia.

PMID- 7726961
TI  - State health spending estimates: concerns from a small state.

PMID- 7726962
TI  - Rational use of new technologies.

PMID- 7726963
TI  - Emergency department treatment of headache.

PMID- 7726964
TI  - New drugs from medicinal plants: opportunities and approaches.

PMID- 7726965
TI  - Thyrotoxicosis--prediction of hypothyroidism.

PMID- 7726966
TI  - Diagnosis of tuberculosis--newer tests.

PMID- 7726967
TI  - Isolation of Ureaplasma urealyticum from low birth weight infants.

PMID- 7726968
TI  - Worsening of the rash of juvenile dermatomyositis with hydroxychloroquine
      therapy.

PMID- 7726969
TI  - Maternal-infant transmission of HIV-1.

PMID- 7726970
TI  - Testing reckless drivers for substance abuse.

PMID- 7726971
TI  - Truth is the daughter of time.

PMID- 7726972
TI  - Gastric emptying in patients with chronic renal failure.

PMID- 7726973
TI  - Visceral leishmaniasis in kidney transplant recipients. An endemic disease.

PMID- 7726974
TI  - Chromium in barley potentiates insulin.

PMID- 7726975
TI  - Omeprazole and the metabolism of caffeine.

PMID- 7726976
TI  - Immunosuppressive treatment of motor neuron syndromes.

PMID- 7726977
TI  - Traditional eye medicines in Sri Lanka.

PMID- 7726978
TI  - Adult diastematomyelia.

PMID- 7726979
TI  - Stents and anticoagulation therapy in diseased saphenous vein grafts.

PMID- 7726980
TI  - Intramucosal pH assessment.

PMID- 7726981
TI  - Transference-countertransference: realizing a love by not actualizing it.

PMID- 7726982
TI  - Aluminium phosphide poisoning.

PMID- 7726983
TI  - Diabetes mellitus--to predict or not to predict.

PMID- 7726984
TI  - Evaluating competence in clinical ethics: is the OSCE the answer?

PMID- 7726985
TI  - Laparoscopic Nissen fundoplication performed in an obese 10-year-old boy.

PMID- 7726986
TI  - Re: Plastic surgery needs more training programs--not less!

PMID- 7726987
TI  - Breastfeeding difficulties.

PMID- 7726988
TI  - Snoring and sleep apnoea.

PMID- 7726989
TI  - AIDS-associated Kaposi's sarcoma. "Duesberg phenomenon'.

PMID- 7726990
TI  - The envelope glycoprotein of HIV-1 alters NMDA receptor function.
AB  - Human immunodeficiency virus (HIV-1) infection often results in central nervous
      system (CNS) dysfunction, yet the mechanism(s) of action for HIV-1 in the CNS are
      not fully understood. In the present study gp120, the HIV-1 envelope
      glycoprotein, was shown to selectively inhibit N-methyl-D-aspartate (NMDA)
      receptor function. In addition to inhibiting radioligand binding to rat NMDA
      receptors, gp120 inhibited NMDA-induced currents in Xenopus oocytes, attenuated
      NMDA-stimulated calcium flux and cytotoxicity in cultured cerebellar granule
      cells, and provided partial protection against NMDA-induced lethality in vivo.
      These findings suggest that NMDA receptor complex is a possible site of action of
      HIV-1 within the CNS.

PMID- 7726991
TI  - Isolation of 3 alpha-hydroxy-3,5-dihydro ML-236C (sodium salt) from paecilomyces
      viridis L-68.

PMID- 7726992
TI  - Phase II trial of LY 186641 in advanced renal cancer.
AB  - LY 186641 is a diarylsulfonylurea with a broad spectrum antitumor activity
      against both murine and human solid tumors. We report here the results of a phase
      II trial of LY 186641 in advanced renal cell adenocarcinoma. The drug was
      administered orally, once daily for 2 weeks, every 21 days at a 700 mg/m2/d dose.
      Sixteen patients were enrolled in this phase II trial; 12 males, 4 females, with
      a median age of 58 years. All patients had progressive measurable metastatic
      disease. The primary tumor was surgically removed in all but one patient. Three
      patients were previously treated by biologic response modifiers (BRMs). A total
      of 72 courses were administered. The most common side effects were
      methemoglobulinemia (MetHgb) and anemia which occurred in 13 and 10 patients
      respectively. The MetHgb did not exceed 15%, and only 3 patients required blood
      transfusion for grade 3 (2 patients) and grade 4 (1 patient) anemia. Reversible
      hepatotoxicity was observed in 3 patients. There were one pathological complete
      response, seven stable disease and 8 progressive disease.

PMID- 7726993
TI  - Commonly asked questions about nightguard vital bleaching.
AB  - There are three basic classes of materials and techniques used for the bleaching
      of vital teeth. These include the in-office bleaching technique with 35 percent
      hydrogen peroxide, the Nightguard vital bleaching technique with 10 percent
      carbamide peroxide, and the over-the-counter bleaching kits with three-to-six
      percent hydrogen peroxide. The most popular of these techniques is Nightguard
      vital bleaching, also referred to as dentist-prescribed, home-applied bleaching.
      This article looks at the current status of the Nightguard vital bleaching
      technique, with a special emphasis on the clinical aspects of the treatment,
      along with the most commonly asked questions concerning the procedure. It would
      still appear than this form of dentist-prescribed, home-applied bleaching, when
      preceded by a proper examination and correct diagnosis, applied with a properly
      fitted prosthesis, and monitored as needed by a dentist, is as safe as other
      accepted dental procedures or commonly ingested foodstuffs.

PMID- 7726994
TI  - Vorozole, a specific non-steroidal aromatase inhibitor.
AB  - Vorozole, the (+)-(S)-isomer of a new triazole compound, is a potent and
      selective aromatase inhibitor. In vitro, the compound is over a thousandfold more
      active than aminoglutethimide. In vivo, the compound very potently inhibits
      ovarian, peripheral, and tumoral aromatase. Vorozole shows an in vitro
      selectivity margin of 10,000-fold for aromatase inhibition as compared to
      inhibition of other P450- and non-P450-dependent reactions. This selectivity was
      confirmed in the rat in vivo. Vorozole, like ovariectomy, almost completely
      reduces tumor growth in the DMBA-induced mammary carcinoma model in the rat. In
      postmenopausal women, vorozole very potently inhibits peripheral conversion of
      androstenedione to estrone. After chronic administration, plasma estradiol levels
      are reduced while the levels of adrenal gluco- and mineralo-corticoids remain
      unchanged. Vorozole has excellent oral bioavailability and exerts linear, dose
      proportional pharmacokinetics.

PMID- 7726995
TI  - [Recent advance in chemotherapy for breast cancer].
AB  - In cases of recurrent progressive breast cancer, ADM, CPM, 5-FU, MTX, MMC and
      vinca alkaloids have proven to be effective, but CMF and CAF have been considered
      the standard chemotherapy regimen. But no regimen can cure recurrent progressive
      breast cancer. Thus, the aim in recent years has been greater efficacy and longer
      survival by means of dose-intensity. The latter has become possible through G
      CSF, the patient's own bone marrow transplant or implantation of peripheral
      vascular cells and the like, resulting in 70-90% efficacy. The CR rate also has
      reached over 50%, and long-term survival has been achieved. Clinical research has
      been thus moving ahead, encouraged by the promise of chemotherapy employing such
      huge doses. However, in combination with other forms of therapy, a great number
      of controversial problems are encountered which require study. Recently, a number
      of agents such as Taxotere or CPT-11 have been used effectively in combination
      for breast cancer, and they appear to be very promising.

PMID- 7726996
TI  - Proteolytic processing of human cytomegalovirus glycoprotein B (gpUL55) is
      mediated by the human endoprotease furin.
AB  - Inhibition of endoproteolytic cleavage of glycoprotein B (gB; gpUL55) of human
      cytomegalovirus was achieved by treatment of infected fibroblasts with decanoyl
      peptidyl chloromethyl ketone (decRVKR-CMK), which inhibits the action of cellular
      subtilisin-like endoproteases with the amino acid recognition motif R x K/R R.
      Uncleaved gB precursor molecules of 160 kDa that were accumulated were
      endoglycosidase H resistant, suggesting that correct cellular transport occurred
      in the presence of the drug. The inhibitor also prevented endoproteolytic gB
      processing in CV-1 cells infected with a recombinant vaccinia virus-gB construct
      (VVgB). Evidence for direct involvement of the ubiquitous subtilisin-like
      endoprotease furin in gB cleavage was obtained from the observation that
      coinfection of CV-1 cells with WgB and a recombinant vaccinia-human furin
      construct reestablished endoproteolytic activity which was normally absent late
      after infection with WgB alone.

PMID- 7726997
TI  - PACAP functions as a neurotrophic factor.

PMID- 7726998
TI  - Role of cysteine 337 and cysteine 340 in flavoprotein that functions as NADH
      oxidase from Amphibacillus xylanus studied by site-directed mutagenesis.
AB  - A flavoprotein from Amphibacillus xylanus catalyzes the reduction of oxygen to
      hydrogen peroxide. Each polypeptide chain in the tetrameric enzyme contains 5
      cysteine residues. The complete reduction of enzyme by dithionite requires 6
      electrons. Such behavior indicates the presence of redox centers in addition to
      the FAD, and these could be disulfides. In order to assess the catalytic role of
      disulfide in the enzyme, 2 of the cysteines (Cys-337 and Cys-340), which show a
      high degree of homology with alkyl hydroperoxide reductase F52a protein and
      thioredoxin reductase, have been changed to serines by site-directed mutagenesis
      of the cloned flavoprotein gene (individually and in a double mutant). Titration
      of the three mutant enzymes, lacking Cys-337, Cys-340, or both cysteines,
      requires only 2 electron eq to reach the reduced flavin state. These results
      indicate the absence of a redox-active disulfide and demonstrate the involvement
      of Cys-337 and Cys-340 in the redox-active disulfide. The catalytic activity of
      the three enzymes was examined by steady-state analysis. The Km for NADH and
      oxygen and the kcat value of these mutant enzymes were essentially the same as
      those of wild type. The NADH oxidase activities were also accelerated markedly in
      the presence of free FAD, which is the case for wild-type enzyme. The NADH:5,5'
      dithiobis(2-nitrobenzoic acid) (DTNB) oxidoreductase activities of all mutant
      enzymes were less than 3% of the activity of wild-type enzyme. The weak DTNB
      reductase activities in the mutant enzymes lacking Cys-337 or Cys-340 may occur
      through direct reduction of the mixed disulfide Cys-337-thiol or Cys-340-thiol
      and nitrothiobenzoate by FADH2. However, the weak DTNB reductase activity in the
      mutant enzyme lacking both cysteines indicates that FADH2 can reduce either DTNB
      or another disulfide directly, albeit inefficiently. These results suggest
      intramolecular dithiol-disulfide interchange reactions in the flavoprotein.

PMID- 7726999
TI  - Comparing conformations at low temperature and at high viscosity. Conformational
      study of somatostatin and two of its analogues in methanol and in ethylene
      glycol.
AB  - The influence of low temperature and high viscosity on the conformation of
      somatostatin and two of its analogues was investigated by 1H NMR in solution. The
      conformation of native somatostatin, a cyclic octapeptide agonist DC13-116 and a
      linear octapeptide agonist were compared in ethylene glycol at 303 K and in
      methanol at low temperature. The first goal of this study was to investigate if
      either low temperature or high viscosity is the more important for the reduction
      of the conformational freedom. Secondly we wanted to compare the amount of
      information concerning the conformation present in both solvents. A larger amount
      of NOESY cross-peaks is observed in ethylene glycol at room temperature compared
      to methanol at low temperature. This indicates that the raising of the viscosity
      is a more important factor in reducing the flexibility of peptides than the
      lowering of the temperature.

PMID- 7727000
TI  - Changes in the activity of NADH-oxidase in rat tissues during experimental
      diabetes.
AB  - The effects of alloxan diabetes and its reversal with insulin treatment, on NADH
      oxidase (E.C.1.6.99.3) was measured in the microsomal fractions of brain, liver
      and kidney at different time interval after diabetes induction. A significant
      increase was found in the enzyme activity in brain and kidney microsomes of the
      diabetic animals, whereas liver showed a decrease. The decrease in the NAD+/NADH
      ratio in the diabetes reported earlier could be due to the changes in the enzyme
      activity as well as other changes in the metabolite concentration.

PMID- 7727001
TI  - Bilateral knee gunshot wounds successfully treated with arthroscopic bullet
      retrieval: a case report.
AB  - One unusual case of bilateral knee joint gunshot wounds caused by a low-velocity
      low-energy missile is presented. Arthroscopic retrieval of the bullets was
      performed resulting in recovery within 5 days.

PMID- 7727002
TI  - The use of the arthroscope as an adjunct in the resection of a chondroblastoma of
      the femoral head.
AB  - We present a case of the use of an arthroscope as an adjunct in the resection of
      a tumor (chondroblastoma) of the femoral head. Use of the endoscope in this case
      allowed preservation of the femoral head and neck. Although the arthroscope has
      been used intraarticularly for the resection of tumors, to our knowledge it has
      not been used endosteally.

PMID- 7727003
TI  - Impingement symptoms caused by a synovial fold in the glenoid fossa projecting
      into the sublabral hole.
AB  - In this case report, an atypical impingement in a 40-year-old male patient with
      terminal restrictions in the shoulder joint is used to show the development of an
      atypical synovial fold through the sublabral hole with protrusion into the
      glenoid fossa.

PMID- 7727004
TI  - Chondromatosis within a meniscal cyst of the knee.
AB  - A 32-year-old man complained of left gonalgia for 2 years and noticed a soft part
      tumor on the lateral side of his left knee. Roentgenograms showed some small
      calcified shadows at the same site of the tumor. Arthroscopy revealed a lateral
      meniscus to be an incomplete discoid with degenerative tears. At the operation, a
      multilocular soft part tumor was noticed in continuity with the lateral meniscus
      macroscopically. Small, loose bodies and gelatinous fluid were found in the
      cavity of the tumor. Histologically loose bodies were chondroma and the soft part
      tumor was meniscal cyst. The meniscal cyst wall contained hyaline cartilagenous
      tissue. Therefore it was thought that chondroma originated from the cyst wall.

PMID- 7727005
TI  - The deadman theory of suture anchors: observations along a south Texas fence
      line.
AB  - Suture anchors are being increasingly reported as a means of fixation of torn
      rotator cuff tendons to bone. The author has developed a mechanical model for the
      suture anchor-rotator cuff construct based on an analogy to the deadman system
      used to stabilize a corner fence post. Using this model, one can demonstrate a
      mechanically favorable angle of insertion of the suture anchor (theta 1) such
      that the anchor's pullout strength is increased at low angles of theta 1. In
      addition, the angle that the suture makes with the direction of pull of the
      rotator cuff (theta 2) has a direct effect on tension in the suture. A low angle
      of theta 2 minimizes the total tension in the suture, thereby minimizing the
      chance of suture breakage.

PMID- 7727006
TI  - Arthroscopic Bankart repair with the Suretac device. Part II: Experimental
      observations.
AB  - Arthroscopic Bankart repair using the Suretac device (Acufex Microsurgical,
      Mansfield, MA) was developed as an alternative to both the staple and suture
      repair techniques. While offering some technical advantages compared with these
      other approaches, it's technical limitations and pitfalls have only been
      described anecdotally based on the clinical experience of several surgeons. The
      purpose of this study was to define these limitations and pitfalls. Eight cadaver
      shoulders underwent arthroscopic Bankart repair using the Suretac device after
      first arthroscopically creating a Bankart lesion. These shoulders were then
      dissected to reveal the placement of the Suretacs and the adequacy of the Bankart
      lesion repair. Glenoids were transected in the transverse plane and embedded in
      clear methylmethacrylate to show placement of the Suretac device relative to the
      articular surface. There were several technical errors that occurred: (1)
      Inadequate abrasion of the anterior and inferior juxta-articular scapular neck;
      (2) inadequate superior and medial shift of the inferior glenohumeral ligament
      before placement of the lowest Suretac, (3) medial placement of the Suretac
      relative to the articular margin; and (4) insufficient capture and compression of
      capsular tissue by the Suretac device. This procedure is technically difficult
      and careful attention must be paid to each step of preparation and repair.
      Recognition of the common errors may help the surgeon to avoid these pitfalls in
      the clinical situation.

PMID- 7727007
TI  - Arthroscopic Bankart repair with the Suretac device. Part I: Clinical
      observations.
AB  - Although arthroscopic Bankart repair has become an accepted surgical
      stabilization technique for anterior shoulder instability, the failure rate
      remains unacceptably high. Little information is available concerning healing of
      the Bankart repair. The purpose of this article is to clarify this issue by
      analyzing a cohort of 15 patients who underwent a "second-look" arthroscopy to
      evaluate and treat pain or recurrent instability following arthroscopic Bankart
      repair with the Suretac device (Acufex Microsurgical, Mansfield, MA). "Second
      look" arthroscopy was performed at an average of 9 months following the index
      surgical procedure. The reasons for this second surgery were recurrent
      instability in 7, pain in 6, and pain and stiffness in 2. In the 7 patients with
      recurrent instability, the Bankart repair was found to be completely healed in 3
      (43%), partially healed in 1 (14%), and had recurred in 3 (43%); however, 6 of 7
      were observed to have lax capsular tissue. In 4 of these cases, retrospective
      review of the index surgical procedure showed that a technical error had been
      made during the repair. Two cases had biopsy of the repair site on "second-look"
      at 6 to 8 months, and this showed residual polyglyconate polymer debris
      surrounded by a histiocytic infiltrate. In the remaining 8 cases with stable
      shoulders, the Bankart repair had completely healed in 5 cases (62.5%) and
      partially healed in 3 cases (37.5%). The higher failure rate with this approach
      compared with open approaches appears to result from improper patient selection
      and errors in surgical technique. There is some question concerning healing
      strength of the Bankart repair, although complete healing of the Bankart does not
      seem to be a prerequesite for shoulder stability. Success of the procedure might
      be expected to improve by selecting only patients with unidirectional,
      posttraumatic, anterior instability who are found to have a discrete Bankart
      lesion and well-developed ligamentous tissue.

PMID- 7727008
TI  - The ultimate strength of suture anchors.
AB  - Suture anchors of various designs are gaining acceptance for open and
      arthroscopic procedures. The rapid proliferation of these devices challenges
      those using them to apply objective criteria for device selection. Comparative
      data on implant security in different settings, modes of failure, and ultimate
      failure strengths is lacking. This study was undertaken to independently develop
      such data for an objective comparison of the suture anchors currently available.
      Using a fresh never-frozen porcine femur model, 10 samples of each of the 14
      different anchors tested were inserted into each of the three different test
      areas; diaphyseal cortex (usually 3- to 4-mm thick), metaphyseal cortex (usually
      1- to 2-mm thick), and a cancellous bone "trough". The suture anchors were
      threaded with 0.018-inch stainless steel wire or, for anchors requiring a more
      flexible suture, 0.018-inch stainless steel 1 x 7 wire braid. Tensile stress
      parallel to the axis of insertion was applied at a rate of 12.5 mm/second by an
      Instron 1321 (Instron Corp, City, State) until failure. Average failure strength
      was calculated for each anchor at each test area. The anchors tested were the
      Mitek G2, Mitek G3, Mitek G4 (Mitek Surgical Products, Norwood, MA), Linvatec
      Revo screw (Linvatec, Largo, FL), Acufex TAG Wedge, Acufex TAG Rod 2 (Acufex
      Microsurgical, Mansfield, MA), Statak models 1.5, 2.5, 3.5, 5.0, and 5.2 (Zimmer,
      Warsaw, IN), Arthrex ESP (Arthrex Inc., Naples, FL), Arthrotek Harpoon, and
      Arthrotek LactoSorb (Arthrotek, Warsaw, IN). The average failure strength of each
      of these anchors in the diaphyseal cortex, metaphyseal cortex, and cancellous
      bone is reported.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727009
TI  - The effects of arthroscopic partial lateral meniscectomy in an otherwise normal
      knee: a retrospective review of functional, clinical, and radiographic results.
AB  - A retrospective review of patients who underwent arthroscopic partial lateral
      meniscectomy for lateral meniscus tears in otherwise normal knees was conducted
      to review the long-term functional, clinical, and radiographic results. Twenty
      six patients (27 knees) were evaluated by questionnaire; 20 patients (21 knees)
      also underwent physical examination and radiographic analysis. Minimum follow-up
      was 5 years and mean follow-up was 8 years. Patient data were obtained from
      detailed questionnaires, knee examinations, and radiographs. Excellent or good
      results decreased from 92% at the time of maximal improvement to 62% at the most
      recent follow-up: 85% of patients were initially able to return to their
      preinjury activity level; however, only 48% were able to maintain this level of
      activity at the most recent follow-up. Seventy-two percent of patients had either
      one or no Fairbank changes and there was no statistical difference when comparing
      radiographic criteria in the operated and nonoperated knee. Early results for
      partial lateral meniscectomy can be quite good; however, significant
      deterioration of functional results and decreased activity level can occur.
      Radiographic changes did not correlate with subjective symptoms and functional
      outcome in our patient population. Our findings suggest that the functional
      outcome for patients undergoing partial lateral meniscectomy may deteriorate with
      time and it may be helpful to counsel patients concerning long-term expectations.

PMID- 7727010
TI  - Assessment of initial fixation of endoscopic interference femoral screws with
      divergent and parallel placement.
AB  - Divergence of the interference screw placement used for femoral fixation during
      endoscopically assisted reconstruction of the anterior cruciate ligament has been
      described. This study is a biomechanical evaluation in 12 pairs of fresh intact
      bovine knees of femoral interference screws placed divergently and parallel
      relative to the bone block and its tunnel. One knee of each pair had the
      interference screw placed in a parallel fashion and the other knee had a 15
      degrees divergence from the bone plug. Paired specimens were used to provide an
      optimal comparison of biomechanical data of the two different screw placements.
      No statistically significant differences were seen between the two groups when
      looking at ultimate load, deformation, and stiffness. Mode of failure was of more
      concern: in 4 of 12 divergent constructs, bone plug pullout occurred compared
      with only 1 of 12 in the parallel construct. The pullout strength remains high
      even with divergence of up to 15 degrees between the bone plug and femoral
      interference screws placed endoscopically.

PMID- 7727011
TI  - Arthroscopic debridement of glenoid labral tears in athletes.
AB  - This is a retrospective study of 46 patients who underwent arthroscopic glenoid
      labral debridement from June 1988 to June 1990. All patients complained of pain
      in the involved shoulder and all were active in sports involving overhead use of
      the shoulder, including 30 baseball players (16 professional, 14 collegiate/high
      school). The average age was 22 years (range 16 to 45) and the average follow-up
      was 2.7 years (range 18 to 50 months). At operation, 35 patients had posterior
      glenoid lesions, 9 had anterior-superior lesions, and 2 had anterior-inferior
      lesions. The posterior lesions were further divided into those that involved a
      horizontal flap tear (n = 19), and those that involved fraying (n = 16). Overall,
      at an average of 31 months follow-up. 54% (25 of 46) of patients had good to
      excellent results. Professional baseball players had a statistically significant
      enhanced outcome with 75% (12 of 16) good-excellent compared with the remaining
      nonprofessional group, with 43% (13 of 30) good-excellent results. Outcome did
      not correlate with shoulder laxity, labral lesion location, mechanism of injury,
      or the presence of a rotator cuff lesion. CONCLUSIONS: Arthroscopic debridement
      of glenoid labral lesions does not yield consistent long-term results.
      Aggressive, supervised physical therapy in highly motivated individuals may be
      the most important factors in influencing outcome in patients having arthroscopic
      labral debridement in the absence of overt shoulder instability.

PMID- 7727012
TI  - Scapulothoracic anatomy for the arthroscopist.
AB  - Because endoscopic management has recently been introduced as treatment for
      painful subscapular snapping, we designed a cadaveric study to identify the
      boundaries of the scapulothoracic spaces and the relationship of important
      neurovascular structures to safe portal sites for arthroscopic surgery. We
      studied eight fresh, unembalmed cadaveric shoulders by anatomic dissection alone
      and eight fresh, unembalmed cadaveric shoulders by dissection after arthroscopy.
      We noted the following findings: (1) the scapulothoracic articulation has two
      triangular spaces, the serratus anterior space and the subscapularis space, that
      are divided obliquely by the serratus anterior muscle; (2) the boundaries of the
      larger serratus anterior space include the chest wall anteriorly, the serratus
      anterior muscle posteriorly, and the rhomboids medially; (3) the boundaries of
      the subscapularis space are the serratus anterior muscle anteriorly, the
      subscapularis muscle posteriorly, and the axilla laterally; and (4) a well
      defined bursa occupies the serratus anterior space. Based on these findings, we
      recommend that portals for arthroscopic surgery should be inferior to the spine
      of the scapula and three to four finger-breadths from the vertebral border of the
      scapula (1) to avoid the neurovascular structures at the superomedial angle of
      the scapula, (2) to avoid the dorsosacpular nerve and artery, and (3) to prevent
      perpendicular orientation of the arthroscope to the lateral chest wall.

PMID- 7727013
TI  - The effects of tibial tunnel placement and roofplasty on reconstructed anterior
      cruciate ligament knees.
AB  - Seventy-five anterior cruciate ligament (ACL) reconstructions augmented with the
      Kennedy Ligament Augmentation Device were evaluated according to classification
      of tibial drill-hole position on the basis of the anatomic landmarks of the ACL
      by two-dimensional radiographic imaging of the fully extended knee. The effects
      of roofplasty to avoid graft impingement were also assessed. The tibial drill
      hole position was classified in relation to the medial intercondylar tubercle on
      anterior-posterior (AP) view, and in relation to Blumensaat's line (B-line) on
      lateral view. Arthroscopic evaluation of the ACL and incidence of chronic
      synovitis as well as Lysholm knee score, manual knee tests, knee extension and
      flexion angles, and knee tester measurements were performed. The results
      indicated that the knee joints in which the tibial drill hole was positioned
      laterally from the medial intercondylar tubercle or in which the tibial drill
      hole was positioned anteriorly to the B-line showed a tendency to develop more
      postoperative chronic synovitis. The knees in which the tibial drill hole was
      positioned anteriorly to the B-line also showed larger AP laxity. There was no
      difference between the non-roofplasty and roofplasty groups.

PMID- 7727014
TI  - Congenital subacromial stenosis.
AB  - Congenital subacromial stenosis is a previously undescribed entity that causes
      narrowing of the height of the subacromial space without proximal migration of
      the humerus. This study comprised 25 shoulders with congenital subacromial
      stenosis. All patients had either an impingement syndrome or rotator cuff tear.
      The average acromiohumeral interval was 4.7 mm. Fifteen of the 25 shoulders (60%)
      had rotator cuff tears. Patients requiring surgery comprised a bimodal age
      distribution: those with an impingement syndrome requiring decompression had an
      average age of 42, whereas those with rotator cuff tears requiring surgical
      treatment had an average age of 66. Study of a separate standard asymptomatic
      population of 84 patients showed that some younger individuals with congenital
      subacromial stenosis may be asymptomatic. However, the natural history seems to
      be a relentless progression to impingement and eventually to complete rotator
      cuff tear. Therefore, subacromial decompression is recommended in younger
      symptomatic individuals to prevent later rotator cuff tear.

PMID- 7727015
TI  - Posterior cruciate ligament tibial inlay reconstruction.
AB  - A patellar bone-tendon-bone tibial inlay reconstruction of the posterior cruciate
      ligament using a popliteal arthrotomy was designed to minimize graft-tunnel wall
      abrasion. Arthroscopic techniques are used for femoral graft fixation. In a small
      series, the procedure decreased the quadriceps active drawer in 70 degrees of
      flexion by an average of 4 mm and improved patellofemoral symptoms.

PMID- 7727016
TI  - The in vivo histology of an absorbable suture anchor: a preliminary report.
AB  - Suture anchors are playing an increasingly important role in attaching tendons or
      ligaments to bone. Anchors are usually made of metallic or other nonbioabsorbable
      materials. The development of an absorbable suture anchor would provide a
      valuable tool for the surgeon; this characteristic would minimize the problems of
      anchor loosening, migration, interference with imaging studies, and the potential
      requirement for later implant removal. This study evaluated the in vivo
      histological response over time of the first generation Arthrex Expanding Suture
      Plug (ESP) (Arthrex Inc, Naples, FL). Suture anchors threaded with nonabsorbable
      No. 2 braided polyester sutures were implanted into ram femurs and removed at
      various intervals over a period of 12 weeks. After preparation, histological
      study showed a gradual healing response in the bone tract. There was no evidence
      of an inflammatory infiltrate or foreign-body reaction during the 12 weeks of
      implantation. A normal bone callus appeared at the insertion tunnel site
      consistent with a fracture-healing response. Later, a fibrous membrane appeared
      at the junction of the implant and the bone tunnel. Over the 12 week interval,
      there was a decrease in osteoblastic activity and the appearance of cavernous
      vascular spaces in the superficial portions of the membrane near the periosteum.
      The ESP anchor composed of poly-L-lactic acid was well tolerated in the in vivo
      setting. Throughout the study, no substantial acute, chronic, or foreign-body
      reaction was observed. These observations are consistent with the expected in
      vivo behavior of poly-L-lactic acid. There is no reason to believe that the ESP
      composed of poly-L-lactic acid should cause a foreign body reaction.

PMID- 7727017
TI  - Palmar uniportal extrabursal endoscopic carpal tunnel release.
AB  - A new technique of endoscopic carpal tunnel release using a 1.5-cm longitudinal
      palmar incision was used in 280 cases. The incision allows identification of the
      superficial palmar arch as well as the median nerve and its branches. A new
      knife/sleeve device that attaches to a standard 4-mm endoscope was created to
      simplify the procedure. The flexor retinaculum is endoscopically divided
      proximally into the distal forearm; the "interthenar fascia" (fascia superficial
      to transverse carpal ligament) can be preserved. Early postoperative results
      include a mean overall return to work and full activity of 14 days. Postoperative
      pinch and grip strengths were near or at the preoperative level by 8 weeks after
      surgery. One third of patients required no postoperative analgesics with minimal
      scar, ulnar pillar, and radial pillar tenderness.

PMID- 7727018
TI  - Arthroscopic synovectomy of the knee: is it helpful?
AB  - We performed 211 arthroscopic synovectomies over a 10-year period. The results
      were assessed at follow-up of at least 2 years using the criteria of pain,
      synovitis, and effusion, range of motion and function. In rheumatoid knees (112
      cases), we had good or excellent results in 80%. However, in seronegative
      arthritides (32 cases), only 60% were successful. Pigmented villonodular
      synovitis was successfully treated with an 11% recurrence rate (19 cases total).
      Synovial chondromatosis (17 cases) had no recurrences. In patients with
      nonspecific synovitis or posttraumatic synovitis, the synovitis was improved in
      60% but only half the patients had pain relief and good function. Looking
      specifically at the posterior portals, there were five complications, all related
      to the posteromedial portal involving the saphenous nerve and vein. Overall
      excellent results can be achieved with due care and attention to detail.

PMID- 7727019
TI  - Meniscus insertion anatomy as a basis for meniscus replacement: a morphological
      cadaveric study.
AB  - A morphological cadaveric study was carried out to gain exact data concerning
      location, shape, and size of the meniscal insertions to bone. Ninety-two knee
      joints were dissected (46 donors; age 18 to 58 years). Peripheral length of the
      menisci, including their insertion ligaments, was measured. The peripheral length
      was 111 +/- 14 mm for the medial and 111 +/- 10 for the lateral meniscus. The
      tibial insertion ligaments for the medial meniscus were fixed in areas that could
      be defined by bony landmarks. The posterior insertion area measured 80 +/- 10
      mm2, the anterior insertion area measured 139 +/- 43 mm2. Bony tibial insertions
      of the lateral meniscus were less well defined. The posterior meniscofemoral
      ligament (Wrisberg) was found in 76% of the knees; the anterior meniscofemoral
      ligament (Humphry) was found in 50% of the specimens. The meniscofemoral
      ligaments in the right knee and the left knee of the same individual were
      frequently different. The anterior transverse ligament was found in 64% of the
      specimens. We concluded that an anatomical attachment of a medial meniscus
      substitute should be possible but to restore the lateral meniscus anatomically
      would be far more complicated.

PMID- 7727020
TI  - [Natural water contents and endemic goiter--a review].
AB  - A review is given of literature which considers water as the cause of endemic
      goitre irrespective of its iodine content and which incriminates goitrogenic
      substances in the water. There are evident connections between the geogenic
      origin of the water and the incidence of goitre insofar as water from shallow
      wells from phyllite, gneiss and slate was linked to an elevated goitre incidence
      as compared to water from igneous rock or from deeper wells with limestone
      underground. Water which caused goitre was often found to be grossly polluted. So
      far, nitrate, humic acids and some of their degradation products have been
      clearly identified to be goitrogenic. Experimental studies by the author
      emphasize the importance of nitrate as well as of humic acids and their
      derivatives as waterborne goitrogens.

PMID- 7727021
TI  - [Burden of fattening pigs and the environment of the pig fattening farms caused
      by lung-passing dust particles, pig stall specific bacteria and ammonia].
AB  - According for their topographic and isolated locations (no built-up area or trees
      down-wind) 13 fattening pig pens with an average stocking rate of 737 (360-2500)
      have been investigated for burden by immission of animals and the environment
      outside the stables up to a distance of 100m downwind of the source. These
      studies have been carried out between June 1988 and April 1989 in monthly
      intervals. The investigated parameters have been: dust of particle size < 5
      microns, stable specific bacteria, ammonia and symptoms of animals respiratory
      diseases. In the stalls could be shown an significant seasonal influence on
      bacteria, lung passing dust content and ammonia concentration with a maximum
      during December/January (1.1 x 10(6) CFU/m3; 0.26 mg/m3; 27 ppm) and minimum
      during June/July (5.7 x 10(5) CFU/m3; 0.075 mg/m3; 11 ppm). In the environment
      outside the pigsties a significant seasonal influence could be found only for the
      stable specific bacteria up to the distance of 100m of the source of emission,
      showing a maximum during fall and winter (1.7 x 10(3) CFU/m3) and minimal
      concentration during spring and summer (9.3 x 10(2) CFU/m3). Due to emission of
      spent air a high significant reduction of the stable specific bacteria and lung
      passing dust concentration could be established outside the stables within a
      distance of 10 m. The content of stable specific bacteria come to 0.2% (1941
      CFU/m3) compared with the amount measured at the air outlet of the spent air
      shaft. At this distance the lung passing dust concentration has been reduced to
      11% (0.016 mg/m3) of the concentration at the emission source. In comparison to
      the examined "neutral air" upwind, the content of lung passing dust downwind has
      not been heightened significantly at any measuring point or time of the year,
      whereas the content of stable specific bacteria downwind was significantly higher
      up to a distance of 50 m (p < or = 0.01). The stable specific bacteria that were
      isolated from the air outside the pigsties, mostly gram positive cocci, had in
      part a strong resistance against Erythromycin, Penicillin, Tetracyclin and
      Ampicillin. The fact that in all investigated farms irritations or diseases of
      the animals respiratory tract in different degrees of intensity could be
      determined shows the urgency to minimize the burden by optimizing the hygienic
      situation inside the stalls. This means especially the colder period of the year,
      because a high frequency of transgression of the ammonia threshold value
      according to German regulations for pig housing could be found in this time.

PMID- 7727022
TI  - Two in-vivo protocols for testing virucidal efficacy of handwashing and hand
      disinfection.
AB  - Whole-hands and fingerpads of seven volunteers were contaminated with poliovirus
      type 1 Sabin strain in order to evaluate virucidal efficacy of different forms of
      handwashing and handrub with alcohols and alcohol-based disinfectants. In the
      whole-hand protocol, handwashing with unmedicated soap for 5 min and handrubbing
      with 80% ethanol yielded a log reduction factor (RF) of > 2, whereas the log RF
      by 96.8% ethanol exceeded 3.2. With the fingerpad model ethanol produced a
      greater log RF than iso- or n-propanol. Comparing five commercial hand
      disinfectants and a chlorine solution (1.0% chloramine T-solution) for handrub,
      Desderman and Promanum, both composed of ethanol, yielded log RFs of 2.47 and
      2.26 respectively after an application time of 60 s, similar to 1.0% chloramine T
      solution (log RF of 2.28). Autosept, Mucasept, and Sterillium, based on n
      propanol and/or isopropanol, were found to be significantly less effective (log
      RFs of 1.16, 1.06 and 1.52 respectively). A comparison of a modified whole-hand
      and the fingerpad protocol with Promanum showed similar results with the two
      systems suggesting both models are suitable for testing the in-vivo efficacy of
      handwashing agents and hand disinfectants which are used without any water.

PMID- 7727023
TI  - Decontamination of dental equipment. A validation of three devices designed for
      cleaning, disinfecting, and lubricating of dental high-speed turbines and
      handpieces.
AB  - This study deals with the decontamination of dental turbines and handpieces (DTH)
      aiming at eliminating the cross-infection risk in dental practice. Three types of
      equipment designed for cleaning/lubricating DTH were validated. The effect of the
      three devices was determined for four different types of DTH, which were
      artificially contaminated with Streptococcus salivarius ATCC 13419 in a
      controlled manner. Sampling was carried out by collecting one ml water flushed
      through the DTH connected to a dental unit. The study resulted in a model for
      testing the decontamination potential of a cleaning/lubrication device for DTH.
      One of the devices could not reduce the contamination, while two others were able
      to reduce the bioburden with at least 3.9 logarithmic steps. However none of the
      devices tested could constantly eliminate the contamination, for which reason an
      additional heat treatment of the DTH is recommended.

PMID- 7727024
TI  - Indicators for microbiologically induced corrosion of copper pipes in a cold
      water plumbing system.
AB  - Corrosion damage in the copper cold-water plumbing system of a large building was
      investigated. An unusual combination of corrosion patterns was found on the inner
      copper pipe surfaces that were in contact with water. Damage was in the form of
      shallow cavities, a surface cover or pinprick-like pits. The corrosion system was
      influenced by thermal treatment and also by cefoxitin dosing. The latter fact in
      particular is a clear indication of microbiological involvement in this corrosive
      action. Different parameters, to be measured in standing water (24-h stagnation),
      are considered typical for this type of corrosion: the detection of Sphingomonas
      spec. and other species in whose cell wall regions copper can accumulate, a
      copper content of more than 2 mg/l, oxygen consumption of more than 4 mg/l and an
      increase in pH. With the help of these indicators, it is possible to recognize
      microbiologically induced corrosion in copper plumbing systems before pipe
      perforation occur.

PMID- 7727025
TI  - Acute and sublethal toxicity of seepage waters from garbage dumps to permanent
      cell lines and primary cultures of hepatocytes from rainbow trout (Oncorhynchus
      mykiss): a novel approach to environmental risk assessment for chemicals and
      chemical mixtures.
AB  - In order to evaluate the suitability of cytopathological criteria in isolated
      fish hepatocytes as endpoints in (eco)toxicological research, liver cells
      isolated from rainbow trout (Oncorhynchus mykiss) by collagenase perfusion were
      exposed in vitro for up to 5 days to sublethal dilutions of two seepage water
      samples collected from garbage dumps. Hepatocytes were analysed with respect to
      acute (lactate dehydrogenase leakage) and sublethal toxicity (electron
      microscopy, stereology). In addition, acute toxicity (24 h) was tested in the
      piscine fibrocytic cell line R1 by means of crystal violet staining and neutral
      red retention. Acute toxicity in R1 cells and isolated hepatocytes could only be
      documented for sample I at dilutions of 1:2 and 1:4. This difference in toxicity
      could be corroborated by cytological alterations in isolated hepatocytes, which
      could be documented for dilutions of 1:100 and 1:8 in samples I and II,
      respectively. Ultrastructural changes were time- and dose-dependent and included
      reduction of hepatocellular volume, disturbance of intracellular
      compartmentation, modified heterochromatin distribution, transformation of rough
      endoplasmic reticulum into concentric membrane whorls, proliferation of lysosomes
      and cytoplasmic vacuoles, as well as reduction of hepatocellular glycogen.
      Although several hepatocellular reactions were found after exposure to either
      sample, the syndrome of ultrastructural alterations allowed clear differentiation
      between the two samples. Results illustrate that cytological effects far below
      macroscopically detectable damage can be discovered not only in intact fish, but
      also in fish cell culture systems. On the basis of the data presented, a multi
      tiered test procedure for aquatic toxicity assessment exclusively based on tests
      with fish cell culture systems is proposed: (1) rapid screening for acute
      toxicity with permanent cell lines; (2) short-term tests with more complex, yet
      more sensitive systems such as primary hepatocytes with straightforward
      biochemical endpoints; (3) prolonged exposure of isolated hepatocytes in
      combination with ultrastructural and biochemical investigations as a sensitive
      tool to detect adverse effects at environmentally relevant toxicant
      concentrations.

PMID- 7727026
TI  - Crystallins: the over-expression of functional enzymes and stress proteins in the
      eye lens.

PMID- 7727027
TI  - The bioremediation of polychlorinated biphenyls (PCBs): problems and
      perspectives.

PMID- 7727028
TI  - The structures and catalytic mechanisms of active-site serine beta-lactamases.

PMID- 7727029
TI  - Enzyme-catalysed lipid modification.

PMID- 7727030
TI  - Enzymes in water-in-oil microemulsions ('reversed micelles'): principles and
      applications.

PMID- 7727031
TI  - Biomedical applications of enzymes and their polyethylene glycol adducts.

PMID- 7727032
TI  - Conjugates of proteins with block co-polymers of ethylene and propylene oxides.

PMID- 7727033
TI  - Liposomes in drug targeting.

PMID- 7727034
TI  - Natural and synthetic saliva: a stimulating subject.

PMID- 7727035
TI  - Methylglyoxal and lipid hydroxperoxide as endogenous cytotoxic molecular species:
      detoxification and regulation of gene expression in yeasts.

PMID- 7727036
TI  - Monoclonal antibody production using free-suspended and entrapped hybridoma
      cells.

PMID- 7727037
TI  - High cell density growth of micro-organisms.

PMID- 7727038
TI  - The genes encoding the major milk-specific proteins and their use in transgenic
      studies and protein engineering.

PMID- 7727039
TI  - Evidence for ras gene mutation in 2-amino-3-methylimidazo[4,5-f]quinoline-induced
      colonic aberrant crypts in the rat.
AB  - Aberrant crypt foci (ACF) are putative preneoplastic lesions that develop after
      treatment of animals with colon carcinogens, including cooked-meat heterocyclic
      amines such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Male F344 rats given
      IQ by gavage on alternating days for 2 wk (130 mg/kg body weight) and killed 12
      wk after the final carcinogen dose had an average of 4.4 ACF/colon and an average
      of 3.2 crypts/focus. The DNA from these ACF was amplified by the polymerase chain
      reaction and analyzed by 3'-primer mismatch and direct sequencing methods for
      mutations in the Ki-ras proto-oncogene. Of the 37 IQ-induced ACF screened, three
      contained a GGT-->GAT mutation in codon 12 and one contained a GGC-->GCC mutation
      in codon 13. The approximately 11% frequency of mutation in IQ-induced ACF is
      within the range of previous ACF studies of azoxymethane, which reported a 7-37%
      incidence of Ki-ras mutation. These findings suggest that for both compounds, ras
      mutations occur during early stages of colorectal tumorigenesis. However, while
      ras mutations can be detected with increasing frequency in azoxymethane-induced
      adenomas and carcinomas, they are reportedly absent in IQ-induced colon tumors.
      Thus, for IQ and related compounds additional factors (possibly increased cell
      proliferation) may be important in the later stages of colorectal tumorigenesis.

PMID- 7727040
TI  - No involvement of Ki-ras or p53 gene mutations in colitis-associated rat colon
      tumors induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate.
AB  - 1-Hydroxyanthraquinone (1-HA), which is present in some herbs, and
      methylazoxymethanol (MAM) acetate, a metabolite of azoxymethane, show synergistic
      carcinogenicity in rat colon, and 1-HA induces ulcerative changes with
      simultaneous severe inflammation of the entire colon. In this study, mutations in
      Ki-ras (exons 1 and 2) and p53 (exons 4-7) were studied by polymerase chain
      reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Of 18
      adenomas and 38 adenocarcinomas induced in male F344 rats (52 tumors induced by 1
      HA plus MAM acetate, three by 1-HA alone, and one by MAM acetate alone), no
      mutations in Ki-ras or p53 were detected under two conditions of PCR-SSCP
      analysis. Because human colon carcinomas from patients with ulcerative colitis
      have a very low incidence of Ki-ras mutation, this experimental system would be a
      good animal model of human colon carcinomas with ulcerative colitis and of human
      colon carcinomas without Ki-ras or p53 mutations.

PMID- 7727041
TI  - Partial restoration of pre-transformation levels of lysyl oxidase and transin
      mRNAs in phenotypic ras revertants.
AB  - Neoplastic transformation mediated by ras oncogenes is associated with
      deregulated expression of genes encoding, for example, various proteases, lysyl
      oxidase, and smooth-muscle alpha-actin. To define the role of these genes in the
      initiation or maintenance of the ras-transformed state, we compared their steady
      state mRNA levels in two different sets of preneoplastic fibroblast lines, ras
      transformed clones, and phenotypic revertants derived from them. Compared with
      the preneoplastic fibroblasts, the ras-transformed derivatives exhibited elevated
      levels of cathepsin L (major excreted protein), transin (stromelysin I, matrix
      metalloproteinase-3), and collagenase I (matrix metalloproteinase-1) mRNA but
      undetectable levels of lysyl oxidase mRNA. Partial restoration of lysyl oxidase
      transcription was observed in four of five phenotypic revertants derived from rat
      FE-8 and NIHpEJcl3 cells. The elevated levels of transin mRNA found in NIHpEJcl3
      cells were diminished to the pretransformation level in interferon revertants but
      were not reduced in phenotypic rat FE-8 revertants expressing a high level of the
      ras oncoprotein. High steady-state levels of collagenase I mRNA were dependent on
      ras expression but were not closely associated with the transformed phenotype.
      High levels of cathepsin L mRNA were associated with neither high ras expression
      nor neoplastic transformation. The downregulation of smooth-muscle alpha-actin,
      characteristic of transformed cell lines, was not reversible in phenotypic
      revertants.

PMID- 7727042
TI  - Inhibition of ras p21 membrane localization and modulation of protein kinase C
      isozyme expression during regression of chemical carcinogen-induced murine skin
      tumors by lovastatin.
AB  - We investigated the ras p21 membrane localization and the expression and
      activation of protein kinase C (PKC) isozymes in activated ras oncogene
      containing tumors and assessed whether these events were related to tumor growth.
      We used 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13
      acetate-promoted SENCAR mouse skin tumors, which were shown to contain Ha-ras
      oncogene activated by point mutation at codon 61, as an in vivo model for these
      studies. Compared with levels in epidermis, highly elevated levels of membrane
      bound Ha-ras p21 were observed in growing tumors, which also showed strong
      expression and membrane translocation of PKC zeta and beta II and weak expression
      of PCK alpha. However, when ras p21 membrane localization was blocked in vivo in
      growing tumors by lovastatin, opposite results were evident. Compared with saline
      treated animals, in which tumor growth continued, lovastatin-treated animals had
      significantly inhibited tumor growth, which led to tumor regression with
      concomitant inhibition of Ha-ras p21 membrane localization. These regressing
      tumors from lovastatin-treated animals also showed a decrease in the expression
      and membrane translocation of PKC zeta and beta II but increased expression of
      PKC alpha. Taken together, our results indicate that ras p21 membrane
      localization and the expression and activation of PKC zeta, beta II, and alpha
      may be the critical events in the regulation of the growth of tumors that contain
      activated ras oncogenes.

PMID- 7727043
TI  - Novel use of a selectable fusion gene as an "in-out" marker for studying genetic
      loss in mammalian cells.
AB  - Recent demonstrations of loss of heterozygosity in a wide variety of human
      cancers suggest that large multilocus genetic deletions (presumably including
      tumor suppressor genes) constitute a major class of genetic alteration in human
      carcinogenesis. Here we show that a bifunctional fusion gene (Hytk), suitable for
      both positive and negative selection, is an effective marker for studying genetic
      loss in mammalian cells with minimal interference from point-mutational changes.
      Studies with a transgenic V79 cell line in which a single functional copy of Hytk
      was stably inserted into the genome in a retroviral vector showed that loss of
      the marker (and presumably flanking cellular genetic material) could be induced
      efficiently by ionizing radiation (gamma-rays and fast neutrons) but only weakly
      by the powerful point-mutagen benzo[a]pyrene diol epoxide. In a first application
      of the system, we provide evidence that radiation-induced loss can occur through
      an indirect mechanism after a high-frequency event. Collectively, our results
      suggest that the Hytk marker should be a valuable tool for studying genome
      position effects on the tolerance of genetic loss in cultured human cells that
      represent different stages in clonal evolution and tumor progression.

PMID- 7727044
TI  - Elevation of transforming growth factor-alpha mRNA and protein expression by
      diverse tumor promoters in SENCAR mouse epidermis.
AB  - The study presented here was designed to further investigate the role of
      transforming growth factor-alpha (TGF alpha) in skin tumor promotion by examining
      the ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) and several non-phorbol
      ester promoters to alter TGF alpha mRNA and protein levels in mouse epidermis.
      Total RNA was isolated from SENCAR mouse epidermis at various times after single
      topical treatments with TPA (3.4 nmol), chrysarobin (220 nmol), okadaic acid (2.5
      nmol), and thapsigargin (8.5 nmol). Northern analyses of these isolated RNA
      samples revealed that all four tumor promoters transiently elevated TGF alpha
      mRNA levels. Whereas TPA, okadaic acid, and thapsigarin elevated TGF alpha mRNA
      levels over similar time courses (peak at 4-8 h), chrysarobin elevated TGF alpha
      mRNA levels with a markedly delayed time course (peak at 24-48 h). More detailed
      studies with TPA also revealed that multiple treatments (four over a 2-wk period)
      transiently elevated TGF alpha mRNA in both the epidermis and the dermis. The
      time courses for changes in TGF alpha mRNA after multiple TPA treatments were
      similar for both tissues. To facilitate studies of altered TGF alpha mRNA
      expression in mouse epidermis and possibly other mouse tissues, a
      semiquantitative reverse transcriptase-polymerase chain reaction method was
      developed. This method faithfully revealed changes in TGF alpha mRNA levels with
      all four tumor-promoting agents similar to those determined by northern blot
      analyses. Immunofluorescence analysis of frozen sections from promoter-treated
      skin revealed elevated TGF alpha protein levels in both epidermis and dermis,
      although staining was most intense in the epidermal layer. Immunofluorescence
      analysis of epidermal hyperplasia adjacent to a full-thickness wound also
      demonstrated significant epidermal TGF alpha staining. Collectively, these
      results indicate that mechanistically diverse tumor promoter stimuli elevate TGF
      alpha mRNA and protein in SENCAR mouse epidermis. Elevated levels of TGF alpha
      may play an essential role in mitogenic stimulation during tumor promotion by
      diverse promoting stimuli.

PMID- 7727045
TI  - p53 status in spontaneous and dimethylnitrosamine-induced renal cell tumors from
      rats.
AB  - Rats carrying the Eker tumor-susceptibility mutation (Eker rats) are predisposed
      to developing renal cell carcinoma. Rats heterozygous for the Eker mutation
      develop spontaneous multiple bilateral renal cell tumors by the age of 1 yr. In a
      previous study, Eker-mutation carrier and noncarrier rats were exposed to the
      renal carcinogen dimethylnitrosamine (DMN), and male rats carrying the Eker
      mutation exhibited a 70-fold increase in the induction of renal adenomas and
      carcinomas when compared with noncarrier rats. In this study, spontaneous and DMN
      induced rat renal cell tumors (adenomas and carcinomas) were analyzed for
      mutations of the p53 gene by direct sequencing of cDNA polymerase chain reaction
      products. There were no mutations in p53 cDNA derived from renal tumors from six
      untreated rats. Mutations were found in one of 15 of the DMN-induced tumors: a
      transition at codon 140, CCT-->CTT, in a renal adenoma. Additionally, seven cell
      lines derived from spontaneous renal cell tumors did not contain mutations in
      p53. The low frequency of p53 mutations (one of 21 renal cell tumors and none of
      seven cell lines derived from renal cell tumors) indicates that the development
      of both spontaneous and carcinogen-induced renal tumors involved a non-p53
      dependent pathway. As p53 is infrequently mutated in human renal cell carcinomas
      and in rat renal mesenchymal tumors, it is likely that a tumor suppressor gene or
      genes other than p53 are involved in the development of renal cancer.

PMID- 7727046
TI  - [Mortality of women of child-bearing age in Costa Rica, 1987-1989].
AB  - The purpose of this descriptive study was to detect regional differences in the
      mortality of women 15 to 44 years of age, especially mortality due to preventable
      causes. The regions studied corresponded to the health regions of Costa Rica. The
      deaths of women 15 to 24, 25 to 34, and 35 to 44 recorded from 1987 to 1989 in
      the National Deaths Register were classified as due to preventable causes or
      nonpreventable causes and grouped by region. The nationwide mortality rate for
      women 15 to 44 years of age was 6.9 per 10,000 women. The highest rates were
      recorded in the Huetar Atlantica (10.05) and Brunca (8.29) regions, and the
      lowest in the West Central region (4.38). Some 44.4% of the deaths were
      preventable, mainly by secondary prevention measures or a mix of measures. The
      lowest proportions of preventable mortality were found in the North Central and
      Brunca regions (35.2% and 36.7%, respectively), and the highest in the West
      Central (64.7%). The nonpreventable deaths mostly corresponded to causes not
      easily avoided and to the remainder of causes not included under other headings
      of the Taucher International Classification. Ill-defined causes represented 1.2%
      of total deaths in the study period. Almost all the peripheral regions showed
      higher mortality than the central plateau, which may be because of their lesser
      degrees of socioeconomic and infrastructure development and of access to health
      services. Another influence may be the more subordinate status of women in rural
      areas. This situation can be changed by making better use of available resources
      and improving the quality of services. It is recommended that this type of study
      be continued in order to monitor trends in women's mortality.

PMID- 7727047
TI  - [Tuberculosis and AIDS in Paraguay].

PMID- 7727048
TI  - [Genetics, individual and society: challenges to social medicine].

PMID- 7727049
TI  - [Health and poverty in Honduras].

PMID- 7727050
TI  - Drug interactions with antacids. Mechanisms and clinical significance.
AB  - Concomitant use of antacid preparations with other medications is common. The
      potential for antacid-drug interactions is dependent upon the chemistry and
      physical properties of the antacid preparation. The intragastric release of free
      aluminum and magnesium ions has potent effects on gastrointestinal function and
      on drug pharmacokinetics. Antacid-drug interactions may occur secondary to
      changes in gastrointestinal motility or alterations in gastric and urinary pH.
      Direct adsorption also results in decreased drug bioavailability. Human drug
      interaction studies are usually performed with healthy volunteers; extrapolation
      of these results to clinical situations may not always be valid. However, the
      current literature would suggest that significant interactions with antacids do
      occur with certain members of the quinolone, nonsteroidal anti-inflammatory drug
      (NSAID) and cephalosporin classes of drugs. Notable interactions also occur with
      tetracycline, quinidine, ketoconazole and oral glucocorticoids. These
      interactions are particularly relevant in the patient with sepsis, cardiac
      disease or inflammatory syndromes.

PMID- 7727051
TI  - Adverse effects of fertility drugs.
AB  - Ovulation-induction agents are commonly used in the treatment of infertility in
      patients with or without ovulatory disturbances. These agents include clomifene,
      bromocriptine, gonadotrophin preparations and gonadotrophin-releasing hormone
      (GnRH) and its analogues. Each agent is associated with its own specific adverse
      effects. Although many of these adverse effects are benign and self-limited,
      some, in particular those effects associated with gonadotrophins, may be life
      threatening. Commonly noted adverse effects encountered with the use of
      pharmacological agents to treat infertility include the following. Clomifene has
      been associated with hot flushes, multiple gestation, visual disturbances,
      cervical mucus abnormalities and luteal phase deficiency. Similarly, most of the
      adverse symptoms associated with bromocriptine are short-lived, such as nausea
      and postural hypotension. On the other hand, gonadotrophin therapy, even when
      used appropriately, may lead to the ovarian hyperstimulation syndrome (which is
      occasionally life-threatening) and a high incidence of multiple gestation.
      Pulsatile GnRH therapy maybe accompanied by similar adverse effects to those of
      gonadotrophins, but with a far lower incidence. With regards to the long term
      safety of these medications, the relationship between fertility drugs and
      epithelial ovarian cancer is controversial, and causality has yet to be proven.
      Indeed, a working knowledge of the many adverse effects associated with these
      medications is essential to any physician prescribing ovulation induction agents,
      in order to ensure maximum patient safety, compliance and understanding.

PMID- 7727052
TI  - The new anticonvulsant drugs. Implications for avoidance of adverse effects.
AB  - Several new antiepileptic drugs offer a worthwhile alternative when standard
      antiepileptic drugs have failed. Suggestions have been made to improve the risk
      benefit ratio of the new antiepileptic agents. More specifically, vigabatrin,
      which is a very useful and well tolerated new antiepileptic drug for refractory
      partial epilepsy, should be started at a low dosage of 0.5 g/day with increments
      of 0.5 g/day every week. Daily dosages exceeding 3 g/day should be restricted to
      patients with improvement. If necessary, the daily dosage of vigabatrin should be
      withdrawn slowly, i.e. by not more than 1 g/week. Lamotrigine is also a
      beneficial new drug for refractory partial and generalized seizures. However, the
      drug is associated with rash. In patients also receiving valproic acid (sodium
      valproate) [which inhibits the metabolism of lamotrigine], the incidence of rash
      can be reduced by slow titration of 25mg every other day for the first week and
      25mg per day for the second week. Rare hypersensitivity reactions, e.g. Stevens
      Johnson syndrome, remain a problem. The risk-benefit ratio of felbamate has
      recently been compromised by fatal aplastic anaemia and fatal liver disease in a
      number of patients. In general, patients should be withdrawn from felbamate, if
      possible, until further clarification of its definitive risk-benefit ratio.
      Finally, gabapentin is a very safe add-on medication. Its remarkably low
      potential to cause adverse effects makes it a welcome addition for the treatment
      of refractory partial epilepsy.

PMID- 7727053
TI  - A risk-benefit appraisal of acarbose in the management of non-insulin-dependent
      diabetes mellitus.
AB  - Acarbose is an alpha-glucosidase inhibitor proposed for the treatment of diabetic
      patients. It acts by competitively inhibiting the alpha-glucosidases in the
      intestinal brush border. The principal action of these enzymes is to convert
      nonabsorbable dietary starch and sucrose into absorbable monosaccharides (e.g.
      glucose). Enzyme inhibitors delay this conversion, slowing the formation and
      consequently the absorption of monosaccharides, and thus reducing the
      concentration of postprandial blood glucose. Both starch and sucrose are
      influenced, whereas lactose and glucose are not. Many studies in experimental
      animals, healthy volunteers and patients with non-insulin-dependent diabetes
      mellitus (NIDDM) have shown that acarbose decreases postprandial blood glucose,
      with a lesser reduction of fasting blood glucose, plasma triglycerides and
      postprandial insulin levels. In long term studies in NIDDM patients, acarbose
      significantly reduced glycosylated haemoglobin levels. Acarbose is only minimally
      absorbed from the gut and no systemic adverse effects have been demonstrated
      after long term administration. The drug allows undigested carbohydrates to pass
      into the large bowel where they are fermented causing flatulence, bloating and
      diarrhoea. These symptoms, which occur in approximately 30 to 60% of patients,
      tend to decrease with time and seem to be dose-dependent. They are minimised by
      starting therapy with low doses (such as 50mg 3 times daily) which may be
      effective in many patients. An increase in serum hepatic transaminases observed
      in earlier studies in the US, where doses of acarbose up to 900mg daily were
      used, has been not reported with the lower doses of the drug actually recommended
      [150 to 300mg (up to 600mg) daily]. In conclusion, acarbose may be useful in
      patients with NIDDM when diet alone is no longer able to maintain satisfactory
      blood glucose control. Furthermore, it may be a valid alternative to
      sulphonylurea or biguanide therapy when these drugs are contraindicated and
      insulin administration may be delayed. Acarbose seems also to be a useful adjunct
      to hypoglycaemic oral agents but its precise role in this field has not been
      fully clarified.

PMID- 7727054
TI  - Idiosyncratic drug-induced haematological abnormalities. Incidence, pathogenesis,
      management and avoidance.
AB  - Haematological dyscrasias remain important because they are potentially fatal.
      Their accurate reporting is required to confirm the cause-effect relationship of
      suspected adverse drug reactions (ADRs); to estimate their incidence; and, by
      risk-benefit analysis of such events, to introduce preventive measures to reduce
      their impact. Limitations within the available data on haematological ADRs are
      reviewed and some suggestions made for improvement. The drugs most commonly
      associated with haematological dyscrasias are listed. An understanding of the
      pathogenesis of haematological dyscrasias is essential for their effective
      management and these are briefly reviewed. Features common to the management of
      the different types of haematological dyscrasia include the early involvement of
      a haematologist and drug information pharmacist and the accurate identification
      and early withdrawal of any likely offending agent. Guidelines for the management
      of drug-induced aplastic anaemia, agranulocytosis, thrombocytopenia and
      haemolytic anaemia are presented and the potential value of granulocyte and
      granulocyte-macrophage colony-stimulating factors (G-CSF; GM-CSF) in the
      management of agranulocytosis is specifically mentioned. Finally, general
      principles are discussed whereby serious haematological ADRs might be prevented.
      These include: the importance of continuing education for drug prescribers;
      policies on the restricted prescribing of likely offending agents; the use of
      written instructions for patients; and, the use of haematological monitoring. The
      guidelines presented in this article should be adapted to meet local
      circumstances and would prove suitable subjects for audit of their effectiveness.

PMID- 7727056
TI  - Omeprazole tolerability.

PMID- 7727055
TI  - Drug-induced torsade de pointes. Incidence, management and prevention.
AB  - Torsade de pointes is a particular form of polymorphic ventricular tachycardia
      causing few haemodynamic symptoms, but carries a poor prognosis because of
      recurrence and sudden death in up to 31% of patients. A wide range of agents have
      been shown to aggravate and even to cause torsade de pointes by prolonging the QT
      interval or increasing QT dispersion. For the majority of substances the
      incidence of torsade de pointes remains unclear, but is of the order of 3 to 15%
      for a wide range of agents. Elicitation of proarrhythmia by drug-induced QT
      prolongation is mainly based on increased cellular excitability and/or abnormal
      dispersion of ventricular repolarisation. Torsade de pointes has been shown to be
      related to bradycardia-dependent early after-depolarisations and/or increased
      dispersion of repolarisation. Clinically, patients with predisposing factors
      prior to medication should be considered at risk of drug-mediated proarrhythmia.
      Typically, torsade de pointes occurs during the first days of antiarrhythmic
      therapy. During this phase, QT interval measurement and assessment of the QTc
      time should be performed frequently. Phases of bradycardia or occurrence of
      ventricular extra beats with a long coupling interval may be of help to identify
      patients at high risk of proarrhythmic events. As a first attempt in managing
      this arrhythmia, magnesium sulphate has been shown to be effective in many
      patients. In case of recurrence of torsade de pointes, the use of a temporary
      pacemaker with pacing at about 100 to 120 beats/min is the therapy of choice
      until the causative agent has been completely eliminated.

PMID- 7727057
TI  - Molecular dynamics simulations suggest that the Eco RI kink is an example of
      molecular strain.
AB  - The energy surface in the vicinity of the "Eco RI kink" was investigated by
      conducting both in vacuo molecular dynamics simulations as well as a simulation
      with explicit solvent. The in vacuo simulations used the "all atom" AMBER 3.0
      force field with a distant dependent dielectric function and "hydrated" counter
      ions while the simulation with explicit solvent used the AMBER 4.0 force field,
      fully charged phosphates and counter ions and a dielectric constant of 1.0. The
      thrust of the simulations was to discriminate between two models of the energy
      surface of the deformed DNA as found in the recognition complex with Eco RI
      endonuclease. In the intrinsic model, the kinked DNA is a local minimum of the
      energy surface intrinsic to the DNA itself while in the strained model there is
      no significant energy barrier separating kinked and regular B-DNA. The two models
      have significant implications for theories of indirect recognition of DNA based
      on sequence-dependent deformability. The simulations suggest that the Eco RI
      kinked structure is an example of molecular strain because it is not near a
      minimum of any of the potential energy functions examined. The simulations leave
      the question of an energy barrier somewhat open and raise the possibility that
      the Eco RI kink is at (or near) a point of dynamic instability of the energy
      surface (either a true maximum or a saddle point).

PMID- 7727058
TI  - Comparison of protein structures in solution using local conformations derived
      from NMR data: application to cytochrome c.
AB  - Structural comparisons of proteins in solution are often required to examine
      structure-functional relationships, study structural effects of mutations or
      distinguish between various forms of the same molecule under different
      conditions. A nuclear magnetic resonance (NMR) based probabilistic strategy is
      presented and used to study the structural differences between the two redox
      states of cytochrome c in solution. A probabilistic approach is employed to
      calculate the main chain conformations of horse ferro- and ferricytochrome c in
      solution, based on the published sequential d connectivity data. Conformational
      differences between the two oxidation states of horse cytochrome c in solution
      are found to be statistically significant. The largest changes in conformation
      are at residues Lys27, Thr28, Leu32, Gln42, Thr47, Tyr48, Thr49, Glu69, Lys72,
      Met80, Phe82, Ile85 and Lys86, all of which are close to the heme (within 14 A of
      the heme iron in the high resolution Xray structure of tuna cytochrome c). We
      suggest that these conformational changes may modulate local dipole moments and
      hence influence the interactions of cytochrome c with its physiological redox
      partners during the electron transfer process. The oxidation state dependent
      conformational differences are found to be much greater in solution than in the
      crystalline state, and the solution and crystal structures differ significantly
      in regions close to the heme. These results suggest that the highly charged
      nature of cytochrome c makes this protein particularly sensitive to the ionic
      strength of its environment and leads to differences between crystal and solution
      structures in the same oxidation state. In such cases, crystal structures must be
      used with caution for modeling molecular interactions in vivo. More generally,
      this analysis indicates that the determination of accurate local conformations
      based on nmr data can provide useful information about structure-functional
      aspects of proteins in solution.

PMID- 7727059
TI  - Interhelical contacts determining the architecture of alpha-helical globular
      proteins.
AB  - An approach based on a presentation of alpha-helical protein topology as a graph
      is presented. The approach allows to estimate a role of each interhelical contact
      in the whole protein topology and to classify the contacts. It is shown that a
      consideration of only about a half of the whole pool of interhelical contacts
      exposed in the protein is enough for a determination of protein architecture.
      Such contacts are called as major and their quantitative characteristics are
      obtained. Moreover, providing a clear and simple presentation of the protein
      topology, the approach can be applied for a description of structural
      domain/subdomain arrangement of alpha-helical proteins and illustration of their
      folding/denaturation paths.

PMID- 7727060
TI  - Characterization of substrate UpA binding to RNase A--computer modelling and
      energetics approach.
AB  - In the past two decades RNase A has been the focus of diverse investigations in
      order to understand the nature of substrate binding and to know the mechanism of
      enzyme action. Although this system is reasonably well characterized from the
      view point of some of the binding sites, the details of interactions in the
      second base binding (B2) site is insufficient. Further, the nature of ligand
      protein interaction is elucidated generally by studies on RNase A-substrate
      analog complexes (mainly with the help of X-ray crystallography). Hence, the
      details of interactions at atomic level arising due to substrates are inferred
      indirectly. In the present paper, the dinucleotide substrate UpA is fitted into
      the active site of RNase A. Several possible substrate conformations are
      investigated and the binding modes have been selected based on Contact Criteria.
      Thus identified RNase A-UpA complexes are energy minimized in coordinate space
      and are analysed in terms of conformations, energetics and interactions. The best
      possible ligand conformations for binding to RNase A are identified by
      experimentally known interactions and by the energetics. Upon binding of UpA to
      RNase A, the changes associated with protein back bone, side chains in general
      and at the binding sites in particular are described. Further, the detailed
      interactions between UpA and RNase A are characterized in terms of hydrogen bonds
      and energetics. An extensive study has helped in interpreting the diverse results
      obtained from a number of experiments and also in evaluating the extent of
      changes the protein and the substrate undergo in order to maximize their
      interactions.

PMID- 7727061
TI  - Human 170 kDa and 180 kDa topoisomerases II bind preferentially to curved and
      left-handed linear DNA.
AB  - The binding activities of the 170 kDa and the 180 kDa human topoisomerases II
      (topo II alpha and topo II beta) to linear DNA fragments with different degrees
      of curvature were characterized. In gel retardation experiments it was shown that
      both forms of the enzyme bind preferentially to a curved 287 bp fragment, forming
      a detectable stable complex. The affinity for straight DNA fragments of similar
      length is significantly lower. Both a commercially available topo II alpha,
      isolated from placenta, and topo II alpha and topo II beta purified from nuclear
      extracts of the Namalwa lymphoma tissue culture line gave similar results. The
      effects of double-stranded poly[d(A-T)], poly[d(G-C)], supercoiled plasmid DNA
      and linear Z-DNA on the topo II-complex with curved DNA were analyzed in
      competition experiments. The hierarchy of affinities of the 180 kDa topo II beta
      for these DNAs has the order: linear left-handed DNA > supercoiled DNA > or =
      curved DNA >> poly[d(A-T)] > poly[d(G-C)]. The 170 kDa topo II alpha binds with
      similar affinity to curved DNA and linear Z-DNA > or = supercoiled DNA >> linear
      B-DNA. The data imply that human topoisomerase II binding is more sensitive to
      DNA secondary structure than to DNA sequence per se. The ability of the enzyme to
      preferentially recognize a wide variety of sequences in unusual secondary
      structures suggests a mode of targeting the enzyme in vivo to regions of high
      negative supercoiling.

PMID- 7727062
TI  - Fluorescence polarization studies of the binding of BMS 181176 to DNA.
AB  - The DNA binding of BMS 181176, an antitumor antibiotic derivative of rebeccamycin
      was characterized by DNA unwinding assays, as well as by fluorescence emission
      and polarization spectroscopic techniques. Unwinding and rewinding of supercoiled
      DNA was interpreted in terms of intercalation of BMS 181176 into DNA. BMS 181176
      shows an enhanced fluorescence emission upon binding to the AT sequence and no
      enhancement upon binding to the GC sequence. BMS 181176 appears to be a weaker
      binder to poly(dAdT).poly(dAdT) compared to doxorubicin and ethidium bromide.
      When bound to DNA, the rotational motion of BMS 181176 is substantially decreased
      as evident from the increase in fluorescence polarization. BMS 181176 exhibits a
      range of binding strengths depending on the DNA. This is demonstrated by the
      Acridine Orange displacement assay using fluorescence polarization.

PMID- 7727063
TI  - Molecular modelling study of DNA-Troeger's bases interactions.
AB  - The two enantiomeric forms: 1R,5R (R) and 1S,5S (S) of the Troeger's base analog,
      9,19-methano-9,10,19,20-tetrahydrodiacridino-[b,f]-[1,5]- diazocine which possess
      a C2 axis of symmetry, are susceptible to interact differently with DNA. This
      paper reports the results of molecular modelling calculations on B DNA-Troeger's
      base complexes. Two interaction modes have been examined: intercalation and
      binding in the grooves. Into the limits of accuracy of such a kind of
      calculations, some tendencies seem to appear. In the intercalation mode, the R
      and S enantiomers exhibit a selectivity for alternating dinucleotidic sequences
      and the minor groove is enantioselective for S. Binding in the major groove is
      selective for S with G-C sequences, and in the minor groove the stereoselectivity
      appears for R with A-T sequences. The S-(dG-dC)5.(dG-dC)5 complex in the major
      groove seems to be the most favoured.

PMID- 7727064
TI  - Fractality of DNA texts.
AB  - By performing several statistical tests, we confirm that long-range correlations
      exist and are typical for long eukaryotic DNA sequences. Different types of
      "critical exponents" for characterization of DNA fractality are discussed. As to
      possible explanation of the phenomenon, our computer simulations indicate that
      simple mosaic structure of genome, without correlations between blocks, cannot be
      solely accounted for the observed statistical properties of DNA texts. We propose
      the concept of "fractal patchiness", which fully explains statistical
      observations, and shed light on the possible origin of long-range correlations in
      DNA sequences.

PMID- 7727065
TI  - G.C base pair in parallel-stranded DNA--a novel type of base pairing: an ab
      initio quantum chemical study.
AB  - It was shown recently that parallel stranded DNA also incorporates the Reverse
      Watson-Crick Guanine. Cytosine (RWC G.C) pair. It contains only one hydrogen bond
      surrounded by mutual carbonyl group and amino group contacts. Here we describe an
      ab initio quantum chemical analysis of this unusual base pair. The conclusions
      can be summarized as follows. (1) The RWC G.C base pair exhibits a previously
      unknown type of DNA base pairing. (2) Its stabilization energy is estimated to be
      above 20 kJ/mol. A significant part of the stabilization originates in attractive
      interactions between the amino group hydrogen atom on one base and lone electron
      pair of the amino group nitrogen atom of the other (opposite) base. (3) In
      contrast to any other base pairing patterns, observed in the DNA molecules, the
      two DNA base amino groups in the RWC G.C base pair are highly nonplanar. They can
      form additional bifurcated hydrogen bonds with neighboring base pairs.
      Coplanarity of the two DNA base rings is energetically acceptable. (4) The unique
      RWC G.C pair cannot be analyzed by the empirical potential calculations.

PMID- 7727066
TI  - Structure sensitivity of amino proton exchange in 2'- and 5' - guanosine
      monophosphate dianions.
AB  - Proton NMR line broadening methods were used to determine the rates of amino
      proton exchange for disordered 2'- and 5' - GMP dianions in aqueous solutions
      containing tetramethylammonium (TMA+) cations. Replacing TMA+ with Na+ does not
      substantially alter the exchange rates, provided that H-bonded, Na(+)-directed
      tetramer structures are absent. Activation enthalpies (kcal/mol) and entropies
      (eu) for 2'-GMP are: delta H not equal to = 18.5 +/- 1.3, delta S not equal to =
      9.6 +/- 4.2 for TMA+ salt at pH 8.10, and delta H not equal to = 14.7 +/- 2.6,
      delta S not equal to = -3.7 +/- 8.0 for the Na+ salt at pH 8.11. Extrapolated
      values of pseudo first-order rate constants at 25 degrees C are in the range of k
      = 1-10 sec-1. At suitable concentrations and temperatures, the Na+ salts of both
      2'- and 5' - GMP formed stacked and unstacked tetramer units. Relative to the
      exchange kinetics observed for the disordered nucleotide, the exchange process in
      the tetramer units was catalyzed in half the amino protons and inhibited in the
      other half. The catalytic process (k > 10(3) sec-1) has been attributed to amino
      protons not involved in interbase H-bonding, where as the inhibited process (k <
      10(-1) sec-1) was assigned to those protons which do form such bonds. The
      structure-catalyzed process in both the stacked and unstacked tetramers was
      manifested by a loss of NMR amino proton intensity due to weighted time-averaging
      with the resonance for bulk water. A bridging water molecule between an amino
      proton and a phosphate on an adjacent nucleotide in the tetramer unit may provide
      a mechanistic pathway for the structure-catalyzed process.

PMID- 7727067
TI  - Thermodynamic and structural properties of r(ACC) as revealed by ultraviolet
      electronic absorption, circular dichroism, 1H-NMR spectroscopy and Monte Carlo
      simulations.
AB  - UV absorption, circular dichroism (CD) and 1H NMR, associated with Monte Carlo
      (MC) molecular structure simulations have been applied to the study of the
      trinucleoside diphosphate: r(ACC). The MC study which has been conducted as a
      function of temperature, is based on random variations of the nucleotide
      conformational angles, i.e. phosphodiester chain torsional angles and sugar
      pucker pseudorotational angles. All of the chemical bond lengths and valence
      angles remained fixed during the structural simulation, except those of the sugar
      pucker. Six different initial structures have been selected in order to explore
      the molecular conformational space as completely as possible. This simulation
      procedure led to distinct families of equilibrium conformations at 283, 298 and
      318 K. The thermodynamical parameters such as variations in entropy, enthalpy and
      also melting temperature (delta SX0, delta HX0 and Tm) of the stacking (X)
      equilibrium were obtained from UV absorption and circular dichroism (CD) spectra
      recorded over a 80K temperature range. Chemical shifts (delta), vicinal coupling
      constants (3Jk,l), and cross-relaxation rate (sigma k,l) of trimers were measured
      at 400.13 MHz over a range of concentrations (2-13 mM) and temperatures (283
      333K). Least-squares fitting of the experimental chemical shifts to simple models
      of association (A) and stacking equilibria allowed separation of the variations
      in the delta values (delta delta X and delta delta A) due to either phenomenon.
      The three NMR data sets (delta delta X, 3Jk,l, and sigma k,l) were then evaluated
      for the minima conformers obtained with the MC stimulations. Theoretical values
      of delta delta X were estimated using the results of an ab initio study while the
      coupling constant data were simulated with Karplus-type equations. Finally, the
      relaxation data were simulated from the distance matrices using treatment for
      cases of both slow conformational exchange accompanied by rapid small-amplitude
      fluctuations about the minima structures. A consistent picture of the large
      amplitude deformations (torsional angle variation) of these trimers has emerged
      from the present study. Optimized conformational blends at 283,296 and 318K were
      obtained by least-squares fitting of the experimental data to the theoretical
      ones, while considering the populations as adjustable parameters. As it would be
      expected, the right-handed helical conformation (A-RNA type) is found to be the
      major stacked species, in the temperature range of 283 to 318K. Limited evidence
      for bulged structures has been obtained, whereas novel reverse-stacked and half
      stacked conformers also presented theoretical data compatible with the NMR
      observables of aqueous r(ACC).

PMID- 7727068
TI  - [Conceptual models, philosophy of care ... only words? The point of view of a
      director of nursing].

PMID- 7727069
TI  - [Conceptual models, philosophy of care. The point of view of a nursing
      professor].

PMID- 7727070
TI  - [From theory to practice: a concrete interiorization experience of the nursing
      process].

PMID- 7727071
TI  - [Training in hospital centers. The students' point of view].

PMID- 7727072
TI  - [The reform of nursing education: an occasion to re-dynamize the school-hospital
      partnership].

PMID- 7727073
TI  - [Everybody's responsibilities in professional development].

PMID- 7727074
TI  - [The patient care team in the pedagogic management of students: a permanent
      challenge].

PMID- 7727075
TI  - [The patient care team in pedagogic management: a permanent challenge].

PMID- 7727076
TI  - [Employment at the end of studies: an end or a means?].

PMID- 7727077
TI  - [Integration of pediatric nursing students in a CPR seminar organized by the
      pediatric intensive care unit].

PMID- 7727078
TI  - [The opening of our hospitals to the European scholarly world].

PMID- 7727079
TI  - [Clinical instruction--a value to preserve. L'equipe enseignante de l'E.I.U.L.B].

PMID- 7727080
TI  - [How to develop and encourage the creativity of our students in our schools and
      hospitals].

PMID- 7727081
TI  - [Which professional competences to answer to health needs of today and
      tomorrow?].

PMID- 7727082
TI  - Pediatric otolaryngology: past, present, and future.

PMID- 7727083
TI  - The Treacher Collins syndrome. A clinical, radiological, and genetic linkage
      study on two pedigrees.
AB  - BACKGROUND: The Treacher Collins syndrome (TCS) is an autosomal dominant
      hereditary syndrome with variable penetrance and expression. The clinical
      characteristics are the result of dysmorphogenesis of the first and second
      embryonal branchial arch systems. The gene responsible has been located on the
      long arm of chromosome 5. Treacher Collins syndrome is rare, and in 60% of the
      patients the family history is negative. Consequently, only a few family studies
      are available. This renders it difficult to make a diagnosis and to comply with
      the increasing demand for genetic counseling. To gain insight into the diagnosis
      and variation in expression and penetrance of TCS, a clinical study was started
      followed by gene linkage research. METHODS: Audiological and physical tests were
      performed on 59 persons belonging to two families. In selected cases (n = 19),
      vestibular and radiological examinations were also conducted. Blood samples were
      taken from 55 persons for gene linkage studies. RESULTS: The diagnosis of TCS
      could be made in 13 persons after clinical examination. The radiological
      detection of zygomatic hypoplasia or aplasia played an important supportive role.
      In addition to the 13 persons with TCS mentioned above, gene linkage studies
      showed positive linkage to chromosome 5q32-33.2 in three persons with clinical
      nonpenetrance. CONCLUSIONS: This is the first time nonpenetrance of TCS has been
      demonstrated convincingly. In individual cases, clinical examination alone cannot
      always remove doubts about the diagnosis. Therefore, gene linkage studies will
      play a decisive role. Identification of the gene responsible for TCS is expected
      to be very useful in clinical practice.

PMID- 7727084
TI  - Transnasal repair of choanal atresia using telescopes.
AB  - OBJECTIVE: Choanal atresia, consisting of a unilateral or bilateral bony or
      membranous septum between the nose and the pharynx, occurs in approximately one
      of 7000 live births. Conventional treatment has consisted of watchful observation
      and elective surgical repair or immediate intervention using a variety of
      surgical techniques. We attempted transnasal repair using a telescope to remedy
      the obstruction. PATIENTS: Over an 18-month period, six female and four male
      patients, who were between 3 weeks and 14 years of age at the time of surgery,
      underwent transnasal repair of unilateral or bilateral choanal atresia with the
      aid of a rod-lens telescope. All 10 patients had nasal stents made from
      endotracheal tubes that were fixed with sublabial and transseptal sutures.
      RESULTS: Seven patients remain free of symptoms 18 to 24 months after surgery.
      Three patients required revision surgery. Two of the revision cases recovered
      completely, with no restenosis 12 months after the second surgery. There were no
      postoperative complications. CONCLUSION: Transnasal repair of choanal atresia
      using a rod-lens telescope appears to be an effective procedure with low
      morbidity.

PMID- 7727085
TI  - Short-stay outpatient tonsillectomy.
AB  - OBJECTIVE: To determine the risk of complications after discharge in outpatient
      adenotonsillectomy after a short (< 6 hours) period of postoperative observation.
      DESIGN: Retrospective chart review. SETTING: Outpatient surgery center at a
      university hospital. PATIENTS: All patients 18 years of age or less who were
      scheduled for adenotonsillectomy or tonsillectomy from January 1988 through
      December 1991. Two hundred fifty-five patient records were reviewed. Twenty-two
      patients were excluded from the study because of various complicating medical
      conditions that required planned overnight hospitalization leaving a study
      population of 233 patients. MAIN OUTCOME MEASURES: (1) Rate and type of
      complications; (2) duration of postoperative observation. RESULTS: Complication
      rates of bleeding, emesis, dehydration, and readmission were compared with rates
      deemed acceptable in the literature (< or = 10%). Power analysis demonstrated
      that the patient number was sufficient to establish a 95% confidence interval for
      a complication rate of 0% to 10%. The mean duration of postoperative observation
      was 136 +/- 48 minutes. Complications included bleeding, emesis, dehydration, and
      nonscheduled admissions. The total complication rate was 9% (95% confidence
      interval, 5.5% to 12.7%). The rate of primary bleeding was 1.4%, and all primary
      bleeding occurred within 75 minutes of arrival in the recovery room; no primary
      bleeding occurred after discharge from day surgery. This complication rate is
      comparable with rates previously described in the literature for patients who
      were observed for a 6- to 12-hour period. CONCLUSION: The findings in this study
      suggest that short periods of observation are safe for outpatient pediatric
      patients undergoing adenotonsillectomy after discharge criteria are met.

PMID- 7727086
TI  - Adenotonsillectomy for treatment of obstructive sleep apnea in children.
AB  - OBJECTIVES: To determine (1) the prevalence of obstructive sleep apnea (OSA) in
      children with a suggestive history; (2) the effectiveness of surgery in treating
      OSA in children; and (3) factors that may help the physician select patients who
      have physiologically significant OSA and are likely to respond to surgery.
      DESIGN: Prospective study. PATIENTS: Sixty-nine children aged 1 to 14 years who
      were referred to the otolaryngologist for evaluation of suspected OSA.
      INTERVENTIONS: Thirty children with a respiratory disturbance index (RDI) greater
      than 5 underwent adenotosillectomy. Twenty-six of the 30 children had follow-up
      polysomnography. MAIN OUTCOME MEASURES: Polysomnography after surgery. RESULTS:
      Thirty-five (51%) of 69 children had an RDI greater than 5 on polysomnography.
      Twenty-six of the 30 children who underwent adenotonsillectomy for OSA had follow
      up polysomnography. All 26 children had a lower RDI after surgery, although four
      patients still had an RDI greater than 5. A preoperative RDI of 19.1 or less
      predicted a postoperative RDI of 5 or less. History and physical findings were
      not useful in predicting outcome. CONCLUSIONS: All patients improved with
      adenotonsillectomy, but patients with the most severe RDI often had many
      respiratory events after surgery. History and physical examination alone are not
      sufficient to assess the severity of OSA or the likelihood of an adequate
      response to surgical treatment.

PMID- 7727087
TI  - Fine-needle aspiration biopsy of cervicofacial masses in children.
AB  - OBJECTIVE: To show the usefulness of fine-needle aspiration biopsy (FNAB) in the
      diagnosis of cervicofacial masses in children. DESIGN: Case series. SETTING:
      Pediatric otolaryngology referral center, ambulatory and hospitalized patients.
      PATIENTS: Seventeen pediatric (age, < 18 years) patients with cervicofacial
      masses. INTERVENTION: Fine-needle aspiration biopsy. OUTCOME MEASURES: Cytologic
      diagnosis, resolution of mass, and need for further surgical diagnosis or
      treatment. RESULTS: Following FNAB, 10 patients underwent open surgery; in seven,
      the surgery was indicated based on FNAB diagnosis; in three, surgery provided
      diagnoses where FNAB was insufficient. Based on FNAB data, seven patients were
      observed without surgery. CONCLUSIONS: Fine-needle aspiration biopsy is a useful
      early step in diagnosing cervicofacial masses in children.

PMID- 7727088
TI  - Acquired laryngeal lesions. Pathologic study using serial macrosections.
AB  - OBJECTIVE: To present the pathologic findings of acquired lesions of the larynx
      in infants. SETTING: The Laryngeal Development Laboratory of Children's Memorial
      Hospital, Chicago, Ill. MATERIALS: One hundred fifteen larynges received at
      postmortem examination from 1975 to 1992. MAIN OUTCOME MEASURE: Acquired
      laryngeal lesions from intubation trauma. TECHNIQUE: Whole-organ serial section
      of larynges. RESULTS: Fifty-three of the 115 specimens exhibited acquired
      laryngeal lesions: 36, submucosal mucous gland hyperplasia; 12, submucosal
      fibrosis; 10, granulation tissue; eight, ulceration; eight, fragmented or
      distorted cricoid; four, cricoid ossification; four, ductal cysts; three, healed
      furrows, and one, anterior glottic synechia. Some specimens exhibited more than
      one type of acquired abnormality.

PMID- 7727089
TI  - Sinus and facial growth after pediatric endoscopic sinus surgery.
AB  - OBJECTIVE: To determine the effect of functional endoscopic sinus surgery (FESS)
      on facial skeletal growth in children. DESIGN: Prospective randomized controlled
      animal study; retrospective histopathologic study of pediatric FESS specimens.
      SETTING: Academic tertiary referral medical center. PARTICIPANTS: Eight newly
      weaned piglets; uncinate and ethmoid bone of FESS specimens from 84 children.
      INTERVENTIONS: The piglets underwent unilateral FESS. When they had developed to
      nearly adult size, computed tomography was used to compare facial and sinus
      development between the surgical and nonsurgical sides. The paranasal sinus
      contents from children were histologically examined to analyze bone types with
      respect to patient age. OUTCOME MEASURES: Sinus development and facial skeletal
      growth after FESS in piglets; histologic maturity of sinus bone in children.
      RESULTS: Facial growth in piglets was significantly reduced on the side treated
      by FESS. When compared with the side that did not undergo the operation, growth
      reached only 57% in the maxillary sinus and 65% in the ethmoid region. Children
      younger than 9 years had woven (immature) bone; children 9 years and older had
      predominantly lamellar (mature) bone. CONCLUSIONS: This preliminary study shows
      that even limited surgery in the anterior ethmoid region can affect sinus and
      facial growth in the piglet. Review of corresponding human histologic specimens
      suggests that further investigation is warranted to rule out the possibility of
      facial and sinus growth disturbance after this surgery in children.

PMID- 7727090
TI  - Craniofacial growth in rabbits. Effects of midfacial surgical trauma and rigid
      plate fixation.
AB  - OBJECTIVE: To examine the effects of soft-tissue manipulation, rigid microplate
      fixation, and multiple osteotomies on the growing midface in rabbits. DESIGN:
      Randomized, controlled experiment. SUBJECTS: Forty 6-week-old male New Zealand
      white rabbits. INTERVENTIONS: Group 1, exposure of the left nasofrontal and
      midzygomatic arch regions with periosteal elevation; group 2, osteotomies at left
      nasofrontal suture and midzygomatic arch; group 3, rigid plate fixation of
      osteotomies; and group 4, rigid plate fixation alone. Animals were killed at age
      20 weeks; growth was assessed by linear and spatial measurements of craniofacial
      regions. RESULTS: Linear data disclosed shortening of the left nasal bone (P <
      .05) in groups 2 through 4. Groups 3 and 4 also had shortened left zygomatic
      arches and orbital diameters (P < .05). Euclidean distance matrix analysis showed
      significant restrictive shape alterations in groups 2 through 4 (P < .05).
      Significant contralateral shape alterations also were found in group 3.
      CONCLUSION: Rigid plate fixation does not cause more severe growth disturbance
      than bony trauma. Use of rigid plate fixation after bony trauma does not seem to
      increase the restrictive effects of trauma on growth. Furthermore, removal of
      rigid plate fixation may not prevent growth disturbances and may induce further
      harmful trauma to the growing midface.

PMID- 7727091
TI  - Antimicrobial activity of silastic tympanostomy tubes impregnated with silver
      oxide. A double-blind randomized multicenter trial.
AB  - OBJECTIVE: To test the null hypothesis that impregnation of tympanostomy tubes
      with silver oxide did not alter the rate of postintubation otorrhea. DESIGN:
      Multicenter, double-blind, randomized clinical trial. OUTCOME MEASURE: Rates of
      postoperative otorrhea during a 1-year study in ears implanted with Silastic
      tubes compared with contralateral, identical tubes impregnated with silver oxide.
      SETTING AND PARTICIPANTS: Eight sites in the United States, 125 children aged 1.5
      months to 12 years who had bilateral otitis media with effusion or bilateral
      recurrent acute otitis media. RESULTS: The overall incidence of postoperative
      otorrhea was 9.78% in the control ears and 5.08% in the ears with silver oxide
      impregnated tubes (P = .01), but no effect was seen during the immediate
      postoperative period. Granulation tissue was seen adjacent to the tube during two
      visits in the ears with standard tubes (0.54%) and during two visits in the ears
      with experimental tubes (0.53%); cholesteatomas did not occur in either group.
      CONCLUSION: Silastic tubes impregnated with silver oxide seem to diminish the
      incidence of postoperative otorrhea in ears requiring long-term ventilation.

PMID- 7727092
TI  - Management of sinusitis in cystic fibrosis by endoscopic surgery and serial
      antimicrobial lavage. Reduction in recurrence requiring surgery.
AB  - OBJECTIVE: An effective treatment program for refractory chronic sinusitis in
      patients with cystic fibrosis has not been achieved. We developed a long-term
      management approach by combining endoscopic surgery with serial antimicrobial
      lavage (ESSAL). DESIGN: In a before and after trial, results of ESSAL in 32
      patients were compared with those of conventional sinus surgery without serial
      antimicrobial lavage in 19 patients. At least 1 year follow-up was available in
      all but one patient. SETTING AND PATIENTS: Patients attending the Stanford
      (Calif) Cystic Fibrosis Center were consecutively referred for otolaryngologic
      evaluation for symptoms and signs of refractory sinusitis. Those subjects who
      were evaluated before 1990 were treated conventionally and afterward by ESSAL.
      INTERVENTION: Conventionally treated patients underwent one or more of the
      following procedures: polypectomy, ethmoidectomy, antrostomy, or Caldwell-Luc
      operation. The ESSAL approach incorporated preoperative rhinosinuscopy and
      computed tomography, endoscopic surgery, a postoperative course of antral
      antimicrobial lavage, and monthly maintenance antimicrobial lavage via brief
      antral catheterization. MAIN OUTCOME MEASURE: Intensity and frequency of sinus
      surgery after initial presentation. RESULTS: The two groups were similar
      demographically and in clinical presentation, including the presence of nasal
      polyposis in 34% and 42%, respectively. The ESSAL group had fewer operations per
      patient, Caldwell-Luc procedures, and a decrease in repeated surgery at 1-year
      (10% vs 47%) and 2-year (22% vs 72%) follow-ups. CONCLUSION: The ESSAL is a
      successful approach to treatment of sinusitis in cystic fibrosis that reduces
      recurrence requiring further surgery for at least 2 years.

PMID- 7727093
TI  - Lymphatic malformations of the head and neck. A proposal for staging.
AB  - OBJECTIVE: To propose a staging system for patients with lymphatic malformations
      of the head and neck. DESIGN: Retrospective chart review. PATIENTS: Fifty-six
      patients were treated for lymphatic malformations from 1983 to 1993 at Children's
      Hospital and Medical Center, Seattle, Wash. The charts were reviewed for anatomic
      location of the lesion, preoperative and postoperative complications, number of
      procedures to control disease, long-term sequelae, and persistence of disease.
      Lesions were characterized as being unilateral or bilateral and suprahyoid and/or
      infrahyoid. The five patient groups were then compared with respect to the above
      categories. RESULTS: Preoperative complications reviewed include preoperative
      infection, respiratory embarrassment necessitating airway intervention, and
      feeding difficulties. Postoperative complications assessed were cranial nerve
      injury, wound infection, and seroma formation. Long-term sequelae included
      malocclusion, speech delay, and cosmetic deformity. The rate of persistent
      disease was also assessed. A staging system was developed based on a progression
      of extent of disease. Stage I patients (n = 12) had unilateral infrahyoid disease
      and a 17% incidence of complications overall. Stage II patients (n = 17) had
      unilateral suprahyoid disease and a 41% incidence of complications. Stage III
      patients (n = 15) had unilateral suprahyoid and infrahyoid disease and a
      complication rate of 67%. Stage IV patients (n = 5) with bilateral suprahyoid
      disease had a complication rate of 80%, while stage V patients (n = 6) with
      bilateral suprahyoid and infrahyoid disease had a 100% incidence of
      complications. CONCLUSION: Anatomic location of lymphatic malformations of the
      head and neck can be used to predict prognosis and outcome of surgical
      intervention.

PMID- 7727094
TI  - Pathologic quiz case 1. Necrotizing sialometaplasia obscuring recurrent well
      differentiated squamous cell carcinoma of the maxillary sinus.

PMID- 7727095
TI  - Pathologic quiz case 2. Tracheobronchopathia osteochondroplastica (TO).

PMID- 7727096
TI  - External septorhinoplasty in children.

PMID- 7727097
TI  - Molecular genetic screening for children at risk of neurofibromatosis 2.

PMID- 7727098
TI  - The role of anaerobes in chronic sinusitis.

PMID- 7727099
TI  - Paediatric dacryocystorhinostomy.
AB  - Of 258 cases of dacryocystorhinostomy performed on children in the period
      September 1981 to September 1991, 130 were for simple, unresolved congenital
      nasolacrimal duct obstruction. Other indications for surgery included punctal
      agenesis, lacrimal fistula, post-traumatic and post-inflammatory canalicular
      obstruction. Of 177 children without canalicular pathology, 171 (96%) were
      relieved of symptoms with one operation, without canalicular intubation. Of 81
      cases with canalicular disease, 55 of 70 (79%) who underwent DCR plus canalicular
      intubation, and 10 of 11 who underwent DCR plus Lester-Jones tube, were
      substantially improved with one operation. No child required peroperative or
      postoperative blood transfusion. Dacryocystorhinostomy in childhood, in
      experienced surgical hands, is a safe procedure, achieving relief of symptoms in
      most cases, particularly in the absence of canalicular disease.

PMID- 7727100
TI  - Corneal astigmatism induced by superior versus temporal corneal incisions for
      extracapsular cataract extraction.
AB  - PURPOSE: We tested the hypothesis that superior corneal sections induce a shift
      to 'against-the-rule' astigmatism and temporal corneal sections lead to the
      preferred 'with-the-rule' astigmatism. METHODS: We conducted a prospective
      randomised trial of superior versus temporal corneal incisions in extracapsular
      cataract surgery in a hospital practice. Thirty nine eyes of 37 patients were
      included. The induced astigmatism was analysed by three methods. RESULTS: When
      analysed by Cravy's method of induced astigmatic cylinders, the superior incision
      induced a greater degree of 'with-the-rule' astigmatic cylinder prior to sutures
      removal on day 77 (P < 0.049). Long term, the temporal incision produced 1.44
      dioptre of 'with-the-rule' astigmatism, while the superior section produced 0.08
      dioptre of 'against-the-rule' astigmatism (P < 0.001). CONCLUSION: The results of
      this small trial indicates that the superior corneal incision produces
      significantly less astigmatism than the temporal incision. The temporal incision
      induces a moderate degree of 'with-the-rule' astigmatism.

PMID- 7727101
TI  - Refractive keratoplasty for post-graft astigmatism.
AB  - Refractive keratoplasty using modified relaxing incisions with compression
      sutures was performed on 33 patients with high post-keratoplasty astigmatism. The
      mean reduction in keratometric astigmatism was 8.38 dioptres from a preoperative
      mean of 12.21 dioptres (SD, 3.59) to 3.93 dioptres (SD, 2.13). All patients noted
      a marked functional improvement. Two patients required reoperation. One patient
      required resuturing. Our modification of undercutting the relaxing incisions
      greatly increases the range of astigmatism that can be treated with this
      technique.

PMID- 7727102
TI  - The long-term results of fistulising trabeculotomy in chronic open-angle
      glaucoma.
AB  - BACKGROUND: Fistulising trabeculotomy has been used for nearly 20 years to
      combine the minimally invasive surgery of trabeculotomy with production of a
      subconjunctival fistula. METHODS: The canal of Schlemm was unroofed 2mm on one
      side of a 3mm half-thickness scleral flap. A trabeculotomy probe was passed about
      30 degrees along the canal on the opposite side and rotated into the anterior
      chamber. RESULTS: Of 99 eyes of 74 patients, 35 eyes of 25 patients were
      available for follow-up at 10 or more years. The mean IOP was 14 +/- 4 mmHg
      (range 7 to 23 mmHg) from a preoperative IOP of 29 +/- 8 mmHg (17 to 60 mmHg).
      Results in 44 similar patients undergoing trabeculectomy and 44 undergoing
      fistulising trabeculotomy were very similar at five-year follow-up. CONCLUSION:
      Fistulising trabeculotomy was effective for lowering intraocular pressure with a
      low complication rate and a large area of subconjunctival fistulisation.

PMID- 7727103
TI  - Efficacy and side effects of botulinum toxin treatment for blepharospasm and
      hemifacial spasm.
AB  - PURPOSE: To analyse the effectiveness and rate of side effects of botulinum toxin
      treatment for blepharospasm and hemifacial spasm. METHODS: In a prospective
      trial, 81 patients with blepharospasm and 70 with hemifacial spasm were treated
      with botulinum toxin A in the neuroophthalmology clinic at St Vincent's Hospital,
      Melbourne. Some 989 treatments were given and the mean follow-up time was 28.7
      months. RESULTS: The duration of action was longer for patients with hemifacial
      spasm than for those with blepharospasm (median 12.0 weeks compared with 7.0
      weeks, P < 0.0001). There was no change in the duration of effect over time with
      repeated treatments of the same dose (F = 0.4, P > 0.05). Once an effective
      dosage was reached, increasing the dose further did not prolong the duration of
      effect. There were no systemic side effects, but there were a number of local
      transient side effects. The most significant side effect was ptosis, which
      occurred in 12% of treatments given to those patients with blepharospasm and
      hemifacial spasm. CONCLUSION: Botulinum toxin is an effective treatment for
      blepharospasm and hemifacial spasm, but there are a number of side effects, the
      most significant being ptosis.

PMID- 7727104
TI  - Edward J Curran and pupillary obstruction.
AB  - PURPOSE: To present the importance of the concepts of Edward J Curran in relation
      to primary angle-closure glaucoma, and include a biographical sketch. METHOD: An
      historical method is adopted. RESULTS: Curran's propositions of pupillary
      obstruction and its relief by peripheral iridotomy were conceded only after 30
      years, and had to await laser surgery for fulfillment. CONCLUSIONS: Edward J
      Curran's name should be enshrined in the history of ophthalmology.

PMID- 7727105
TI  - Albipunctatus retinopathy in inherited interstitial nephritis.
AB  - We describe here a patient with familial interstitial nephritis and albipunctatus
      retinopathy. Albipunctatus is often seen in patients with Alport syndrome, which
      is an X-linked disorder characterised in affected males by renal failure by the
      age of 25, high-tone sensorineural deafness, anterior lenticonus and
      albipunctatus. The diagnosis of Alport syndrome depends on the electron
      microscopic appearance of a trabeculated glomerular basement membrane (GBM); and
      mutations have been demonstrated in the gene for the alpha 5 chain of type IV
      collagen. In the familial interstitial nephritis described here, the inheritance
      was autosomal dominant, renal failure developed in middle age, and there was no
      associated hearing loss or anterior lenticonus. The finding of albipunctatus
      retinopathy in this patient suggests that the genetic mutation responsible
      involves a protein common to both retinal and interstitial basement membranes. In
      addition, we conclude that the demonstration of albipunctatus in an individual
      with familial nephritis does not necessarily indicate that the underlying disease
      is Alport syndrome.

PMID- 7727106
TI  - Ophthalmodynamometry and corticosteroids in central retinal vein occlusion.
AB  - PURPOSE: This is the first report of the monitoring of the clinical progress of a
      central retinal vein occlusion by measuring the retinal venous collapse pressure
      using ophthalmodynamometry. METHOD: A 38-year-old woman with a nonischaemic
      central retinal vein occlusion received systemic prednisone. The dose of
      prednisone was increased and decreased both abruptly and gradually. The response
      was monitored by weekly measurements of visual acuity, retinal appearance and
      retinal venous collapse pressure. The retinal appearance was assessed by
      comparison of repeated stereo colour photographs and fluorescein angiographs.
      Retinal venous collapse pressure was estimated by taking the mean of four or more
      ophthalmodynamometric measurements. RESULTS: An inverse relationship between the
      ophthalmodynamometric retinal venous collapse pressure and systemic prednisone
      dosage was observed. The visual acuity and retinal appearance remained unchanged
      throughout the follow-up. CONCLUSIONS: Ophthalmodynamometry in this case was a
      useful method of quantitatively monitoring the response of central retinal vein
      occlusion to systemic prednisone. The response would not have been detected if
      only visual acuity and retinal appearance were used to monitor the progress.

PMID- 7727107
TI  - Ocular migraine in an eight-year-old girl.
AB  - BACKGROUND: A case of ocular migraine in an eight-year-old girl is presented.
      This is believed to be the youngest reported patient with ocular migraine.
      CONCLUSION: The choroid was noted to darken during an episode of visual loss,
      suggesting choroidal ischaemia as the cause of the visual loss.

PMID- 7727108
TI  - Orbital impalement by steering wheel lock.

PMID- 7727109
TI  - The second two hundred cases of endocapsular phacoemulsification: the learning
      curve levels off.

PMID- 7727110
TI  - A method of estimating optic disc diameter.

PMID- 7727111
TI  - Combinatorial multiple cassette mutagenesis creates all the permutations of
      mutant and wild-type sequences.

PMID- 7727112
TI  - Efficacy of tetracycline-controlled gene expression is influenced by cell type.

PMID- 7727113
TI  - REN display, a rapid and efficient method for nonradioactive differential display
      and mRNA isolation.

PMID- 7727114
TI  - Efficient one-tube RT-PCR amplification of rare transcripts using short sequence
      specific reverse transcription primers.

PMID- 7727115
TI  - PCR-based production of a ribozyme to plasminogen activator inhibitor-1.

PMID- 7727116
TI  - Efficient production of internal standard DNA for quantitative PCR using an
      automated sequencer.

PMID- 7727117
TI  - Single-tube method for plasmid miniprep from large numbers of clones for direct
      screening by size or restriction digestion.

PMID- 7727118
TI  - Purification of DNA from Mycobacterium species without sonication or phenol.

PMID- 7727119
TI  - Recovery of mitochondrial and nuclear DNA from archived allozyme samples.

PMID- 7727120
TI  - Rapid construction of nested deletions of recombinant plasmid DNA for dideoxy
      sequencing.

PMID- 7727121
TI  - Cycle DNA sequencing from a gel band.

PMID- 7727122
TI  - Fluorometric method for the measurement of nuclease activity on plastic plates.

PMID- 7727123
TI  - Rehydration of dried polyacrylamide gels.

PMID- 7727124
TI  - Improved factor Xa cleavage of fusion proteins containing maltose binding
      protein.
AB  - The addition of five glycine residues at a position adjacent to the factor Xa
      cleavage site of a MBP-2C fusion protein, comprising maltose binding protein
      (MBP) and poliovirus 2C, allowed factor Xa to generate both of the component
      proteins. If, however, MBP-2C was without the above modification, it was cleaved
      only at a site located internally within poliovirus 2C, and this protein was not,
      therefore, generated by factor Xa cleavage. A simple procedure is described that
      uses PCR for the introduction of five glycines adjacent to the factor Xa
      recognition site.

PMID- 7727125
TI  - Rapid screening of open reading frames by protein synthesis with an in vitro
      transcription and translation assay.
AB  - The analysis of open reading frames (ORFs) to predict full-length or truncated
      proteins in genes is conventionally achieved by DNA sequencing. This method
      becomes labor-intensive when a large number of specimens or when large genes are
      to be examined. To circumvent this problem, we used an in vitro transcription and
      translation (TT) assay to identify full-length or truncated proteins in PCR
      amplified genes. A total of 47 nef genes from the simian immunodeficiency virus
      (SIV) were cloned from 13 SIV-infected monkeys and were screened for ORFs by
      using the TT assay. Of these 47 genes, 20 had an intact ORF and 27 had premature
      stop codons at variable positions in the nef gene. All 20 nef genes with intact
      ORFs produced full-length proteins, while truncated proteins of different sizes
      were synthesized from all 27 nef genes with premature stop codons. In addition,
      we validated a simplified TT protocol that allows the direct screening of ORFs
      from transformed bacterial colonies, thus eliminating the need for plasmid
      preparations. By being rapid, simple and cost-effective, this technique should be
      widely applicable to examine the integrity of the ORF of any gene.

PMID- 7727126
TI  - Simple plaque hybridization method for the detection of differentially
      represented repetitive DNA.
AB  - A differential DNA hybridization method of detecting moderately repetitive strain
      specific or species-specific DNA is described. Two Drosophila melanogaster
      strains, one with and one without transposable elements, were utilized as a model
      system to demonstrate the effectiveness of this procedure. A genomic library was
      constructed from flies of the pi 2 strain, which contains both P and hobo
      transposable elements. Duplicate plaque lifts of this library were probed with
      DNA from the same strain and with DNA from the Canton-S strain, which contains
      neither of these two families of transposable elements. Plaques that hybridized
      stronger to the genomic DNA that contained elements were noted, and then the
      filters were stripped and reprobed with P and hobo element DNA. Many of the
      differentially hybridizing plaques were shown to contain DNA homologous to one of
      the two known elements. This method should allow the isolation and cloning of any
      repetitive DNA present in one species or isolate, but absent or present in
      reduced copy number in another species or isolate. By analogy to the recent
      invasion of D. melanogaster by P elements, such differentially represented DNA is
      likely to represent recently invading transposable elements that are actively
      mobile.

PMID- 7727127
TI  - Rapid and efficient screening for p53 gene mutations by dideoxy fingerprinting.
AB  - Dideoxy fingerprinting (ddF) is an efficient method for detecting single base and
      other sequence changes in PCR-amplified DNA segments. This screening method is a
      hybrid between single-strand conformation polymorphism analysis (SSCP) and Sanger
      dideoxy sequencing. It involves a Sanger sequencing reaction with one
      dideoxynucleotide followed by non-denaturing gel electrophoresis. We are using
      ddF to screen for mutations in the p53 tumor suppressor gene in primary breast
      cancers. ddF detected more than 100 mutations in different regions of the gene,
      including all types of single-base mutations and microdeletions/microinsertions
      of various sizes. Furthermore, ddF reliably detected heterozygous mutations, if
      the region of interest was screened in both directions. In a blinded, prospective
      study, ddF detected all 25 mutations within exons 4-10 and adjacent flanking
      intronic regions previously found by direct sequencing. ddF was also useful in
      scoring two common polymorphisms within the p53 gene. Guidelines for preventing
      false-positive and false-negative results are summarized.

PMID- 7727128
TI  - PCR cycle sequencing protocol for population mitochondrial cytochrome b analysis.
AB  - Laboratories intending to adopt cycle sequencing of PCR products in their routine
      analysis often face a confusing range of methods and kits. Through the study of
      mitochondrial cytochrome b, we have shown that clean and highly reproducible
      sequences could be obtained by using a combination of existing simple and
      economical methods in the preparation of DNA templates, PCR, purification of PCR
      products and sequencing. Our protocol is useful in itself or as a standard in
      typing other PCR-amplified DNA at the population level.

PMID- 7727129
TI  - Resin-purified digoxigenin-labeled DNA probes: an efficient protocol for mapping
      and fingerprinting sugarcane.
AB  - Nonradioactive Southern blotting using digoxigenin (DIG) has become routinely
      applied to the analysis of single-copy genes for genetic mapping because it is
      fast and safe. Previous studies indicate that DIG-labeled probes are suitable for
      single-gene detection in less complex genomes, but their efficient application to
      mapping a large octoploid genome has not been discussed. We developed a stream
      lined procedure for nonradioactive restriction fragment length polymorphism
      mapping and DNA fingerprinting of sugarcane that combines DIG-11-dUTP and anion
      exchange chromatography. In this report, we show that anion-exchange
      chromatography provides a reliable and simple technique for the resin
      purification of large numbers of DIG-labeled DNA fragments 0.3-3.0 kb in size,
      and it is essential in minimizing contaminants and nonspecific signal.

PMID- 7727130
TI  - DNAOPT: a computer program to aid optimization of DNA gel electrophoresis and SDS
      PAGE.
AB  - Several methods and computer programs have been developed for estimating the size
      of DNA fragments from gel electrophoresis. However, methods are lacking that may
      facilitate in optimization of gel conditions. In this article, a computer program
      called DNAOPT is described, which was developed to assist researchers in tuning
      the gel conditions of gel electrophoresis. The DNAOPT program fits the reciprocal
      of the migration distance vs. the size of the DNA fragments using the hyperbolic
      regression method and computes the hyperbolic parameters such as signal, flatness
      and capacity (optimization parameters). The program further manipulates these
      parameters obtained by running gel electrophoresis under various conditions (i)
      to determine the relationship between the gel conditions (temperature, buffer
      concentration, electric field strength, etc.) and optimization parameters; (ii)
      to demonstrate gel electrophoresis curves and optimization parameters
      graphically; and (iii) to represent the optimizing parameters at different gel
      conditions in tabular form. The above-mentioned program options aid the users in
      selecting optimum gel conditions by running the gel repeatedly under various
      conditions in which the agarose concentration, electric field strength,
      temperature, buffer concentration and so on are varied in a systematic way for
      each set of gel conditions. Similarly, this program can also be used to optimize
      gel conditions of sodium dodecyl sulfate polyacrylamide gel electrophoresis.

PMID- 7727131
TI  - HPLC analysis of synthetic oligonucleotides using spectral contrast techniques.
AB  - The need for high-purity oligodeoxyribonucleotides for various applications has
      resulted in the development of novel synthesis, purification and analytical
      techniques. A diversity of methods, including polyacrylamide slab gel
      electrophoresis, capillary gel electrophoresis, as well as HPLC, have been
      successfully used to analyze material throughout the purification process. This
      study demonstrates how the application of spectral comparison techniques to
      synthetic products resolved by anion-exchange HPLC can distinguish deletion
      fragments (i.e., "N-1" sequences) from full-length products. Such analysis
      techniques can also differentiate partial from fully phosphorothioated DNA
      sequences. In combination, HPLC separation and spectral analysis technology
      provide information not obtainable with any other single analytical method.

PMID- 7727132
TI  - High-performance membrane chromatography.
AB  - In gradient chromatography for proteins migrating along the chromatographic
      column, the critical distance X0 has been shown to exist at which the separation
      of zones is at a maximum and band spreading is at a minimum. With steep gradients
      and small elution velocity, the column length may be reduced to the level of
      membrane thickness--about one millimeter. The peculiarities of this novel
      separation method for proteins, high-performance membrane chromatography (HPMC),
      are discussed and stepwise elution is shown to be especially effective. HPMC
      combines the advantages of membrane technology and high-performance liquid
      chromatography, and avoids their drawbacks.

PMID- 7727133
TI  - Phosphor image analysis of human p53 protein isoforms.
AB  - Phosphor imaging was evaluated for detection, quantitation and resolution of
      multiphosphorylated protein isoforms separated by two-dimensional gel
      electrophoresis. A nuclear phosphoprotein, p53, was isolated by
      immunoprecipitation after biosynthetic labeling with 35S, 32P or 33P in cultured
      human cells. Of the three radionuclides, 35S was the most sensitive in detection
      after a 1-week exposure, although shorter exposure times were effective. In
      dividing cells, 11 35S-labeled isoforms were found, of which 10 were
      phosphorylated by 33P and 32P. Exposure of phosphonuclides for one half-life
      showed that 33P radiolabeling produced better resolution among isoforms than 32P
      but was less sensitive in detection. Volume integration showed phosphorylated
      isoforms comprised from 1% to 25% of total isoform signal. The relative
      phosphorylation of each p53 isoform was estimated by normalizing 33P or 32P
      isoform volumes with the corresponding 35S volume and showed progressive
      phosphorylation of acidic isoforms. Additionally, phosphor imaging capably
      detected quantitative changes among individual isoforms after experimental
      modulation of the isoform pattern by serum deprivation. The described
      electrophoretic isolation and quantitation procedures should find general
      application in discerning active and inactive phosphoisoforms for eventual
      identification.

PMID- 7727134
TI  - In situ hybridization with digoxigenin-labeled RNA probes: facts and artifacts.
AB  - We have developed an easy, stream-lined yet sensitive protocol for in situ
      hybridization to mRNA in frozen tissue sections or cytospins using digoxigenin
      labeled RNA probes detected by alkaline phosphatase. We found the crucial
      parameters for successfully performing this technique to be tissue quality,
      fixation time and effective removal of excess probe. Most preparation, incubation
      steps and washes as described in the literature were found to be unnecessary and,
      therefore, eliminated, making this protocol simple enough to be achieved in any
      laboratory with access to tissue preparation and some molecular biology
      expertise.

PMID- 7727135
TI  - HPLC preparation of highly purified single-stranded M13 DNA.
AB  - Closed-circular, single-stranded viral DNAs are widely employed in DNA cloning
      and sequencing experiments. Because of their well-defined structure and sequence,
      closed-circular, single-stranded DNAs have also been used for ligand binding
      experiments and light scattering measurements. However, there is a high molecular
      weight impurity observed in light scattering experiments, which sometimes
      contaminates single-stranded DNA purified from phage that has been precipitated
      in polyethylene glycol, average molecular weight 8000, and purified by standard
      phenol-chloroform extraction. Three methods have been examined that remove this
      impurity from closed-circular, single-stranded M13mp19 DNA (SS M13 DNA). One
      employs a commercial peparation. This procedure yields pure but degraded SS M13
      DNA, as shown by light scattering measurements and HPLC. Another employs a
      Whatman DE52 (diethylamino cellulose) column. This procedure yields intact DNA,
      but in poor yield (less than 20% of that obtained by phenol-chloroform
      extraction). The last was the most successful. This employs HPLC with a Waters AP
      1 column with DEAE 8HR bedding. This procedure, which provides DNA in high yield
      (80%-90% column recovery) with an intact structure, is an efficient method for
      the isolation of high-purity, closed-circular, single-stranded viral DNA suitable
      for physical investigations and ligand binding measurements.

PMID- 7727136
TI  - Double-stranded DNA analysis by capillary electrophoresis with laser-induced
      fluorescence using ethidium bromide as an intercalator.
AB  - We have developed a rapid and sensitive method to analyze double-stranded DNA by
      capillary electrophoresis equipped with a laser-induced fluorescence detector.
      Using ethidium bromide as an intercalator in polyacrylamide gel-filled
      capillaries along with a green He/Ne laser source (excitation: 543 nm; emission:
      600 nm), we found the detection sensitivity for a single DNA-ethidium bromide
      complex was in the picogram level with a resolution of one base pair separation
      between two DNA fragments. In the case of the separation of a phi X174 DNA-HaeIII
      digest, sizes from 72 to 1353 bp were well resolved within 12 min. For the
      analysis of PCR-amplified DNA, low levels of amplified DNA fragments could be
      detected that could not be visualized in agarose gel after standard ethidium
      bromide staining. Considering the high resolving power and sensitivity, we
      believe that this method can be a useful tool for the analysis of double-stranded
      DNA especially for PCR-amplified DNA fragments.

PMID- 7727137
TI  - Agarose gel electrophoresis of high molecular mass protein complexes.

PMID- 7727138
TI  - Innovations in non-isotopic DNA sequencing: using an electrotransfer unit to blot
      sequencing gels and an automated membrane processor for detecting DNA sequences.
AB  - As alternatives to radiolabeled DNA sequencing, chemiluminescent and chromogenic
      sequencing methods can be comparable in both sensitivity and resolution.
      Chemiluminescent/chromogenic detection procedures are safer because they
      completely eliminate the handling and use of radioisotopes. One method involves
      standard dideoxy DNA sequencing reactions that are initiated with biotinylated
      primers, separated by gel electrophoresis, transferred onto nylon membrane and
      detected utilizing chemiluminescent 1,2-dioxetane substrates for alkaline
      phosphatase. Alkaline phosphatase is linked to the biotinylated sequencing
      products by a streptavidin/alkaline phosphatase conjugate (SAAP). In this paper
      we describe an optimized procedure for transferring sequencing gels. The
      procedure is based on a semidry method developed at Hoefer Laboratories using the
      GeneSweep Sequencing Gel Transfer Unit. Transfer is rapid, uniform and reliable
      from gel to gel. We also describe automation of the development process using a
      fully programmable Gel/Membrane Processor that automates delivery, incubation and
      disposal of reagents. All crucial points for electrotransfer of sequencing gels
      and the detection of biotinylated DNA sequencing reaction products are discussed.

PMID- 7727139
TI  - Results of heart-lung transplantation in children with cystic fibrosis.
AB  - Children with cystic fibrosis represent the largest group referred for, and
      undergoing, heart-lung transplantation at our institute. Between June 1988 and
      July 1993, 76 patients were accepted for transplantation, of whom 25 were
      transplanted, while a further 36 died waiting. Those transplanted ranged from 5
      18 years of age and included 13 males and 12 females. Organs were used from
      donors matched by ABO blood group, size and cytomegalovirus (CMV) status. Post
      transplant maintenance immunosuppression comprised cyclosporin A, azathioprine
      and prednisolone. Anti-thymocyte globulin and high dose methylprednisolone were
      given peri-operatively and for acute rejection episodes. Actuarial survival was
      67% at 1 year, 61% at 2 years and 54% at 3 years. Obliterative bronchiolitis (OB)
      has occurred in 13 patients (52%) and was the major cause of mortality and
      morbidity. In three patients, OB was associated with the development of tracheal
      anastomotic stenosis. Other complications included diabetes mellitus (n = 9),
      pancreatitis (n = 1) and hypertension (n = 8). Despite these problems, those
      surviving the first year post-transplant showed a mean FEV1 of 71% (compared to
      29% pre-transplant) and enjoyed an overall improved quality of life.

PMID- 7727141
TI  - The effects of cardiopulmonary bypass on systemic and coronary levels of von
      Willebrand factor.
AB  - Von Willebrand factor antigen (vWF Ag) is a marker of endothelial injury which
      has been shown to rise during surgical procedures, including cardiopulmonary
      bypass (CPB). The aim of this study was to determine whether intermittent aortic
      cross-clamping during CPB causes the release of vWF Ag from the coronary vascular
      bed, which would suggest coronary vascular endothelial cell perturbation. Fifteen
      consecutive patients undergoing CPB with aortic cross-clamping during coronary
      artery bypass surgery and/or valve replacement by the same surgeon were studied.
      Paired venous and coronary sinus samples were taken pre- and post-thoracotomy,
      prior to cross-clamping on CPB, and 1, 5 and 10 minutes after release of the
      aortic cross-clamp. Plasma vWF Ag (IU/ml) was measured by ELISA. Venous vWF Ag
      measured prior to skin incision was 0.75 +/- 0.11 IU/ml (mean +/- SEM) and fell
      to 0.53 +/- 0.07 IU/ml after institution of CPB but prior to aortic cross
      clamping (P < 0.01 vs pre-incision sample). Coronary sinus vWF Ag measured prior
      to aortic cross-clamping was 0.54 +/- 0.06 IU/ml (P = NS vs paired venous
      sample). At 1, 5 and 10 min after release of the aortic cross-clamp there was a
      progressive rise in vWF Ag in both venous and coronary sinus samples (1 min: 0.67
      +/- 0.05 IU/ml vs 0.75 +/- 0.10 IU/ml, 5 min: 0.73 +/- 0.07 IU/ml vs 0.76 +/-
      0.09 IU/ml, 10 min: 0.74 +/- 0.08 IU/ml vs 0.79 +/- 0.09 IU/ml; P = NS venous vs
      coronary sinus, respectively). Levels of vWF Ag were highest immediately prior to
      the termination of CPB (venous: 0.95 +/- 0.12 IU/ml; coronary sinus: 0.91 +/-
      0.14 IU/ml). We conclude that cardiac surgery using CPB with aortic cross
      clamping is associated with a progressive rise in coronary sinus and venous
      levels of vWF Ag.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727140
TI  - P300-mapping--a neurophysiological tool to quantify cerebral dysfunction after
      coronary artery bypass grafting.
AB  - Objective parameters are needed to quantify cerebral dysfunction following
      cardiac surgery in outcome and comparative studies. In this investigation we
      assessed the value of the late auditory evoked potentials N100 and P300 to
      measure the neuropsychological deficit after coronary artery bypass grafting
      (CABG). N100, an exogenous potential is influenced by the stimulus pattern
      (frequency, intensity and stimulus presentation rate). P300, an endogenous
      potential, depends on the cognitive processing invoked by the stimulus. With
      approval of the Human Investigation Committee and the patients' consents, 52
      subjects undergoing elective CABG were enrolled. Operation, extracorporal
      circulation, anesthesia and postoperative intensive care were standardized.
      Twenty-channel recordings of N100 and P300 were obtained for off-line analysis.
      P300 was elicited using an oddball paradigm with rare target tones interspersed
      among frequent non-target tones. Additionally, neuropsychological tests (syndrome
      short test SKT and letter cancellation test) were carried out. Neurological
      examination and all tests were compared preoperatively and one week
      postoperatively. A significant deterioration in cerebral function was documented
      by the SKT score (P = 0.04), an increase in P300 latency (P = 0.004) and an
      increase of mistake rate in counting the P300 target tone (P = 0.02). No
      differences between preoperative and postoperative testing were found for letter
      cancellation, P300 amplitude and any N100 parameter. No correlation was found
      between the preoperative/postoperative changes in SKT score and P300 latency.
      P300 was proved to be an objective neurophysiological parameter that allows for
      the quantification of cerebral function after CABG.

PMID- 7727142
TI  - Arterial and venous cytokine response to cardiopulmonary bypass for low risk CABG
      and relation to hemodynamics.
AB  - During and after cardiopulmonary bypass (CPB), cytokines may affect cardiac
      performance and the immune response and are therefore of diagnostic and
      therapeutic interest. We have used EIA/EASIA kits to measure arterial and venous
      levels of interleukin-1-beta (IL-1-beta), IL-2, IL-2 receptor (IL-2-R), IL-6,
      tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in 12 men and 3
      women (mean age 59.4 +/- 8.5 years, mean left ventricular ejection fraction 66 +/
      11%, average of 2.5 +/- 0.64 vessels affected by disease) undergoing elective
      coronary artery bypass grafting (CABG). On average each patient received 3 +/-
      0.85 bypass grafts and required a postoperative maximum dopamine-dose of 3.8
      micrograms/kg per min. Mean CPB and operation times were 60 +/- 21 min, and 132
      +/- 16 min, respectively. During CPB, the venous levels of IL-2 temporarily
      decreased from 234 to 0 (p < 0.05) pg/ml and arterial and venous levels of IL-2-R
      temporarily decreased from 28 to 16, and 36 to 18 pM (p < 0.05), respectively.
      After termination of CPB, there was an increase in the arterial and venous levels
      of IL-6 from below 3 to 253 and 277 pg/ml (p < 0.05) and TNF-alpha from 1.1 to
      5.7 and 0.7 to 4.0 pg/ml, respectively (p < 0.05). Tumor necrosis factor-alpha
      increases peaked 30 min, and IL-6 increases peaked 4 h after termination of CPB.
      Twenty-four hours after the end of CPB, IL-6 showed a tendency to return to
      baseline, but still remained significantly elevated.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7727143
TI  - Consistent non-pharmacologic blood conservation in primary and reoperative
      coronary artery bypass grafting.
AB  - Because much interest has been focused on blood conservation using different
      drugs and complicated blood cell processing devices, we analyzed our results with
      the use of a non-pharmacologic, simple and inexpensive program for blood salvage
      in 2326 patients undergoing myocardial revascularization. The material was
      divided into two groups: patients undergoing a primary coronary bypass operation
      (Group P, n = 2298) and a smaller subset of patients undergoing repeat coronary
      bypass operation (Group R, n = 28). At least one internal mammary artery was
      grafted in 99% of the patients, with supplemental saphenous vein grafts.
      Intraoperatively, autologous heparinized blood was removed before bypass and
      retransfused at the conclusion of extracorporeal circulation. The volume
      remaining in the extracorporeal circuit was returned without cell processing or
      hemofiltration. Autotransfusion of the shed mediastinal blood was continued
      hourly up to 18 h after surgery in all patients. The mean postoperative
      mediastinal drainage in group R was 543 +/- 218 ml, compared to 703 +/- 340 ml in
      Group P (P = 0.01). In Group R, 1 patient (3.6%) received packed red cells and no
      patients were given other homologous blood products, compared to 33 patients
      (1.4%) given red cells and 35 patients (1.5%) given plasma transfusion in Group P
      (NS). Thus, in total, 2257 patients (97.0%) were not exposed to any homologous
      blood products during hospitalization. Total hemoglobin loss was significantly
      higher in Group R, resulting in a mean hemoglobin concentration at discharge of
      109 +/- 13 g/l, compared to 121 +/- 14 g/l in Group P (P = 0.0002).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7727144
TI  - Cardiac surgery in patients under chronic hemodialysis.
AB  - A total of 15 chronic renal failure patients on hemodialysis therapy underwent
      some kind of cardiovascular surgery between August 1984 and March 1993. Ten had a
      valve abnormality, and the remaining five had coronary artery disease. All of
      them were hemodialyzed the day before surgery and 24-48 h after the operation.
      Eleven recovered well after surgery, four died of septic shock: two of these were
      in septic shock prior to surgery; one was in acute congestive heart failure, and
      one was operated during an acute myocardial infarction. All operative deaths
      occurred in the patients who underwent non-elective surgery or were
      preoperatively in New Heart Association (NYHA) class IV. The factors having an
      impact on morbidity and mortality seem to be more related to the previous
      clinical situation and to the urgency of the operation than to the status of
      chronic renal failure. An early and adequate assessment of the candidates, when
      possible avoiding emergency surgery and acute left ventricular dysfunction, as
      well as careful management during cardiopulmonary bypass procedures (CPB) and the
      immediate post-surgical period will certainly improve the result of cardiac
      surgery in these patients, making it similar to those who are not in chronic
      renal failure.

PMID- 7727145
TI  - An unusual opportunity to reduce operative risk by combining cardiac and
      pulmonary procedures.
AB  - A case is presented of a successful triple combined procedure consisting of
      coronary artery bypass grafting, mitral valve replacement and pulmonary
      resection. Previous studies have shown the increased risk of surgery for coronary
      occlusive disease when combined with mitral valve replacement or when undertaken
      in the presence of obstructive lung disease. We believe this to be the first
      report describing the reduction of operative risk as a result of combining
      pulmonary resection with mitral valvular and coronary artery surgery.

PMID- 7727146
TI  - "Yellow nail syndrome" associated with chronic recurrent pericardial and pleural
      effusions.
AB  - The authors describe a case of yellow nail syndrome in a 44-year-old male
      patient, with a clinical picture characterized by hand and foot onychodystrophy,
      lymphedema in the legs and recurrent pleural and pericardial effusions. They
      indicate subxiphoid pericardiostomy and pleural drainage as the rational surgical
      procedure for the treatment of this particular associated pathology.

PMID- 7727147
TI  - Optimizing muscle synchronization after dynamic cardiomyoplasty. Two educational
      cases.
AB  - Muscle stimulator programming is fundamental in ensuring optimal latissimus dorsi
      graft function after cardiomyoplasty. The ventricle-muscle synchronization delay
      has a significant effect on graft function, but can be difficult to optimize. The
      established method for ensuring appropriate synchronization involves the use of M
      mode echocardiography. We present two educational cases in which M-mode and
      Doppler echocardiography have been instrumental in illustrating
      electrophysiologic and haemodynamic factors which need to be considered in
      evaluating an appropriate synchronization delay.

PMID- 7727148
TI  - Modification of the Senning repair in a case of transposition of the great
      arteries with juxtaposition of the atrial appendages.
AB  - A further modification of the Senning operation is described in a case of
      transposition of the great vessels with juxtaposition of the atrial appendages in
      which the right atrial appendage was excised and used as a free graft in the
      construction of the venous pathways.

PMID- 7727149
TI  - Should transoesophageal echocardiography be part of the cardiac surgeon's
      repertoire?

PMID- 7727150
TI  - Papillary fibroelastoma of the mitral valve associated with rheumatic mitral
      stenosis.
AB  - Papillary fibroelastoma of the mitral valve diagnosed and treated in life is
      extremely rare. There have been eight cases documented so far. We report the
      first case of a mitral valve papillary fibroelastoma associated with severe
      rheumatic mitral stenosis and tricuspid regurgitation with stenosis. The tumor
      arose from the posteromedial papillary muscle of the mitral valve. The mitral
      valve was replaced after excising the valve with the tumor and the tricuspid
      valve was repaired. The patient did well and remains asymptomatic.

PMID- 7727151
TI  - Late re-interventions following arterial switch operations in transposition of
      the great arteries. Incidence and surgical treatment of postoperative pulmonary
      stenosis.
AB  - Seventy-six patients were studied after arterial switch operation (ASO) between
      May 1977 and February 1992. Pulmonary artery reconstruction was initially
      performed by: conduit interposition in 5 patients, direct main pulmonary artery
      anastomosis and button patches in 60 patients, and pantaloon-like patch repair in
      11 patients. Pulmonary stenosis developed in 17 patients (22%), requiring a total
      of 26 late re-interventions. Re-intervention was required in four out of five
      patients operated with pulmonary artery conduits, 11 out of 60 with a button
      patch repair and 2 out of 11 following pantaloon-type repair. In this series
      pulmonary artery stenosis (PS) involving the pulmonary valve occurred in 9/17
      patients. Involvement of the pulmonary valve was related to the technique of
      pulmonary artery reconstruction. In these patients surgery is necessary. Balloon
      angioplasty can be a valuable tool when the stenosis is more distal. The
      incidence of PS was not influenced by the type of reconstruction or the use of
      Lecompte's maneuver.

PMID- 7727152
TI  - [Excitatory amino acids and neuronal death].
AB  - Glutamic acid has been believed to be an excitatory transmitter in the mammalian
      central nervous system (CNS), and has been implicated in the pathogenesis of
      neuronal damage in the mammalian CNS. There are two major classes of glutamate
      receptors, ionotropic (iGluR) and metabotropic glutamate receptors (mGluR).
      Participation of iGluRs in glutamate mediated neurotoxicity has been well
      documented. However, much less is known about participation of mGluRs than the
      case for iGluRs. The physiological roles of mGluRs have been believed to regulate
      transmitter release and to modulate the function of iGluRs through activating
      various intracellular second messenger system. Recently we have discovered
      several potent agonists for mGluRs which would provide additional information
      about glutamate mediated neurotoxicity. DCG-IV, one of the most potent mGluR
      agonists, alleviated kainate-induced limbic motor seizures in extremely low doses
      in the rat, but the dose response curves showed a bell typed one. DCG-IV also
      demonstrated severe sedative condition and markedly prolonged the sleeping time
      in halothane anesthesia. DCG-IV depressed the duration of after-discharges and
      the seizures evoked by electrical stimulation in the amygdala kindling rat. DCG
      IV significantly decreased in number of kainate-induced degenerated neurons in
      the area of hippocampal CA1, amygdala and septum when DCG-IV was continuously
      applied into the ventricule. In conclusion, activation of mGluRs leads the
      alleviation of neuron damage induced by iGluR agonists.

PMID- 7727153
TI  - [Two dimensional analysis of neural activities by calcium imaging].
AB  - The development of fluorescent Ca2+ indicators made us possible to measure the
      intracellular Ca2+ concentration easily. Furthermore the analysis of fluorescent
      images obtained by a fluorescence microscope became easy and popular, because of
      the tremendous development of computers and related hardwares. Time courses and
      topographical differences in Ca2+ concentration can be demonstrated as two
      dimensional color-coded images. Such images are sometimes quite persuasive. That
      is just "Seeing is believing". We can detect a completely new site of biological
      phenomena through this method. This article will describe many different types of
      Ca2+ indicators and applications to biological image analysis. Especially the
      method called "macro" image analysis can demonstrate the regional difference in
      changes of the Ca2+ concentration of slice preparation during medical treatment
      of cerebral ischemia. Already more than ten years have passed since the first
      demonstration of a fluorescent Ca2+ indicator, quin 2, and the methods using such
      Ca2+ indicators become important in the field of experimental biology.

PMID- 7727154
TI  - [Analysis of functional architecture of the brain by optical recording methods].
AB  - To date, our understanding of the elaborate mechanism that governs the
      information processing of neural tissue or the brain is based mainly on data
      obtained from single-electrode recordings in vivo or in vitro. The refinement of
      electrophysiological techniques has advanced our knowledge about neural
      information processing, but clearly, we are still far from complete and coherent
      understanding of these brain functions. Although conventional approaches have
      provided the bulk of our knowledge about neural information processing, there is
      clearly a need for research tools that are better suited to investigate the
      detailed properties of individual neurons on the one hand and allow for studying
      the interactions between large numbers of neurons on the other hand. The use of
      optical recording methods with voltage-sensitive dyes (extrinsic optical signal
      recording) seems to be one of the most promising ways to attack the above
      problems. This approach allows to record the neural activity at many sites
      simultaneously and thus provides spatio-temporal information about the flow of
      electrical activity in a given preparation. The optical recording without using
      voltage-sensitive dyes, intrinsic optical signal recording, is also useful to
      detect the neural activity in the brain. The signal is thought to be originated
      from the metabolic change of the brain tissue which is associated with the change
      in neural activity. We compared the both activity mapping obtained with extrinsic
      signals and intrinsic signals. This kind of trial seems to be useful not only for
      understanding the origin of the metabolic signal, but also for treating the data
      obtained with PET or functional MRI.

PMID- 7727155
TI  - [Clinical application of magnetoencephalography in pediatric neurologic
      diseases].
AB  - Electrical activities develop simultaneously with the establishment of magnetic
      fields following Biot-Savart's law. Excitation of cerebral neurons causes the
      development of electrical activities, and thereby produces magnetic fields. The
      term "magnetoencephalography (MEG)" refers to the detection and study of these
      magnetic fields. It is therefore possible to estimate accurately the origins of
      the magnetic fields, i.e. deep foci of electrical activities, from the outside of
      the scalp. This report describes the principle of magnetoencephalography, the
      recording method, and the estimation of intracerebral localization for rolandic
      discharges in benign childhood epilepsy with centrotemporal spikes.

PMID- 7727156
TI  - [Metabolic and functional magnetic resonance imaging of the brain: clinical
      application to pediatric brain diseases].
AB  - We have developed 1H-chemical shift imaging (CSI) and functional magnetic
      resonance imaging (FMRI) methods on a clinical MRI system, in which metabolic and
      functional information can be obtained from the brain. 31P- and 1H-CSI are in
      clinical use. Using 1H-CSI, the peaks of N-acetylaspartate (NAA), choline (Cho)
      and creatine (Cr) are clearly detected in multiple small voxels. In normal
      children, the ratio of NAA/Cho increased after birth in different manners in
      different parts of the brain. The peak of NAA decreased in some disorders with
      brain damage or neuronal immaturity. It has been shown recently that functional
      activation of the cortex can be visualized with MR imaging with a blood oxygen
      level dependent (BOLD) effect. At an activated area, the ratio of deoxyhemoglobin
      to oxyhemoglobin decreased in the capillary and venous beds. Therefore, with a
      decrease of the effect of the T2 susceptibility from deoxyhemoglobin, the signal
      intensity of the activated area increased. CSI and FMRI have a unique possibility
      in the field of non-invasive brain analysis.

PMID- 7727157
TI  - [In vivo visualization of neurotransmitter function in the human brain by PET].
AB  - Measurement of cerebral blood flow and energy metabolism using PET with 15O and
      18F labeled tracers allows quantitative evaluation of cerebral metabolism that
      can be perturbed in pathological states. Neurotransmission is a new target that
      is visualized by labeling of substrates of enzymes that are involved in
      neurotransmitter synthesis or degradation. Neuronal receptors are mapped by
      introducing the labeled ligands that are specifically bound to the receptors in
      question. We developed unique tracers that label dopamine D2 or histamine H1
      receptors. With other available ligands for the muscarinic cholinergic receptors
      and [18F] fluorodopa, we started clinical investigations to document the state of
      neurotransmission in patients with epilepsy, Parkinson's disease and dementia.
      Using [11C] doxepin we observed an increase of H1 receptors in the epileptic foci
      that showed decreased glucose metabolic rate at the interictal phase. This
      phenomenon is compatible with reported increase of mu opiate receptors in the
      brains of epileptic patients. Brain uptake of FDOPA (Ki), calculated by the
      graphical plot was found relatively stable with age both in the normal population
      and dementia patients. However, the striatal Ki of FDOPA of severely demented
      patients significantly reduced, compared with the normal aged subjects. The
      correlation analysis between FDOPA Ki and severity of dementia as assessed by
      mini-mental state examination revealed a significant reduction of Ki associated
      with the disease progression. Increase in D2 receptor density as assessed by the
      uptake of YM 09151-2 was observed in cases with reduced FDOPA uptake, which may
      correspond to the state of supersensitivity of the D2 receptors.

PMID- 7727158
TI  - [Molecular pathology of neurogenetic diseases].
AB  - Recently, techniques of molecular biology have been widely applied to child
      neurology, and a new aspect of the pathogenesis of neurogenetic diseases has been
      revealed. In this article, recent results of molecular analysis in my laboratory
      were briefly reviewed on hereditary beta-galactosidase deficiency. After cDNA
      cloning, a number of gene mutations have been identified; mainly missense
      mutations, such as single-base substitution, duplication, insertion, and splice
      site mutation. A clear phenotype-genotype correlation was established for some
      mutations specific to the late-onset forms of the disease. Intracellular events
      of mutant proteins expressed by these mutant genes were heterogeneous, and
      expected to be closely connected to the pathogenesis of each phenotype. On the
      basis of these data, a unified clinical classification was proposed for GM1
      gangliosidosis and Morquio B disease, together with a new concept of "beta
      galactosidosis" for the diseases with beta-galactosidase gene mutations.

PMID- 7727159
TI  - [Wilson's disease--evolutive panorama of diagnosis and treatment in the last
      forty years].
AB  - In 1912, Wilson and Fleischer independently reported autopsied patients with
      progressive neurological disorder associated with cirrhosis of the liver, and
      they proposed that the syndrome could be a specific disease of toxic origin. In
      1952, Scheinberg demonstrated a deficiency of serum ceruloplasmin in Wilson's
      disease, and it became possible to diagnose the illness while the patient was
      still asymptomatic. In 1956, Walshe introduced penicillamine as the most
      excellent drug for treatment of the disease. These epoch-making discoveries
      encouraged Japanese physicians to make early diagnosis and to try prevention of
      the disease. This lecture was to review the changing panorama in the diagnosis,
      treatment and prognosis of the disease in the period of forty years focusing on
      the experiences in Japan. Early detection of the patients based on
      hypoceruloplasminemia made it possible to investigate the onset ages of an
      elevation of serum GOT or GPT and the appearance of Kayser-Fleischer (KF) rings.
      So far, the youngest patients who exhibited high GPT level and KF rings were
      three years and five years old, respectively. It became popular that an
      unexpected elevation of serum transaminase in apparently healthy children of
      three years or more prompted to examine the possibility of Wilson's disease, and
      an increasing number of non-familial patients in late infancy have been detected.
      Now, the mass-screening for Wilson's disease is in progress. Follow-up studies on
      the prophylaxis for more than thirty years definitely proved that the appearance
      of clinical symptoms was prevented with the continued penicillamine
      therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727160
TI  - Findings of scientific misconduct.

PMID- 7727161
TI  - [Risk factors of peptic ulcer hemorrhage].
AB  - A retrospective analysis is made of the risk factors in 229 patients admitted to
      hospital with hemorrhage from peptic ulcer. The factors that have been studied
      are: 1) age. 2) type of ulcer lesion. 3) associated disease. 4) antiinflammatory
      intake. 5) prior ulcer symptoms. 6) intensity and outcome of the bleeding
      episode. 7) endoscopic findings. 8) treatment modality. 9) mortality. The
      analysis of these factors tries to establish, by means of the square chi test
      with Yates correction, the possible relations between the factors, to determine
      which ones will have a pronostic value. From the results obtained we conclude
      that the factors with the highest pronostic importance are: 1) With respect to
      the severity of the bleeding episode, antiinflammatory intake and duodenal
      location of the ulcer lesion. 2) With respect to the need for urgent surgical
      treatment, antiinflammatory intake and prior ulcer symptoms. 3) With respect to
      mortality, severity, persistence and recurrence of bleeding, and the need for
      urgent surgical treatment. Finally, it is important to mention the absence of
      pronostic value, with respect to mortality, of advanced age and the endoscopic
      findings of active and/or recent bleeding.

PMID- 7727162
TI  - [Morphometric study of somatostatin-producing "D" cells in duodenum and pancreas
      of the rat, following experimental antrectomy].
AB  - Given the inhibition of gastric secretion by the "D" cells producing somatostatin
      in antral mucosa, as well as evidence of disorders of the postprandial blood
      glucose after antrectomy, we may expect as a result of the antral resection a
      series of modifications in the content of the "D" cells in duodenum and pancreas.
      The study group was made up of 30 Sprague-Dawley albino rats, distributed in 3
      groups as follows: Billroth I, Billroth II and laparotomy. The "D" cell study and
      the morphometric analysis after immunohistochemical avidin-biotin, was carried
      out with an automatic image analyzer and a morphometric calculation program. The
      results show that: the "D" cell population decreased significantly in the B-II
      group while the number of pancreatic islets and the average insular surface, did
      not show significantly differences in the tree groups, the relationship of the
      average insular surface with respect to the pancreas, decreased significantly in
      the two groups with antrectomy, expressing a hyperplasia of the exocrine pancreas
      and that the number of insular "D" cells decreased significantly in the B-II
      group and didn't change in the B-I group. These findings suggest that antrectomy,
      originates an increase of the exocrine pancreas and that antrectomy with
      gastrojejunal anastomosis excluding the duodenum, decreases the number of
      duodenal "D" cells and number of "D" cells of the pancreatic islets.

PMID- 7727163
TI  - [Changes in plasma levels of intestinal regulatory peptides following colonic
      resection in the rat].
AB  - The colon is considered as an endocrine organ producing regulatory peptides.
      Colon resection exerts an influence on remnant bowel including proliferative
      adaptive phenomena. The aim of this work was to determine the modifications of
      several regulatory peptides after colectomy and its relation with the
      gastrointestinal proliferative changes. 75% proximal colectomy was performed in
      Wistar rats. Seven groups were used according to sacrifice times: 24 h, 48 h, 72
      h, 7 days, 14 days, 21 days and control group without resection. Results show
      significant decreases in somatostatin, neurotensin and cholecystokinin plasma
      levels maintained up to 21 days postsurgery. Gastrin is elevated with a highest
      peak at 72 h achieving basal levels at 21 day. Peptide YY show significant high
      levels between 72 h and 7 days. Secretin plasma levels are increased 24 h post
      surgery, decreasing significantly at day 14. It is suggested that maintained low
      plasmatic levels of somatostatin, a known mucosal growth inhibitor, after
      colectomy may help the proliferative adaptation.

PMID- 7727164
TI  - [Morphopathological changes before and after biliodigestive derivation in
      experimental cirrhosis induced by biliary ligation in the rat].
AB  - OBJECTIVE: Study of the hepatic morphological and biochemical changes in an
      experimental model of cirrhosis in rat by ligation of the common bile duct before
      and after bilioduodenal anastomosis. DESIGN: Ligation of the common bile duct in
      a group of 80 female Wistar rats during 30 days. Liver biopsy for histological
      studies and staining, blood samples for biochemical determination were taken, and
      a bilioduodenal anastomosis was constructed. 30 days later new liver specimens
      and blood samples were taken. A control group consisted of 10 rats. RESULTS: 30
      days after biliary obstruction histological changes were characterized by
      occurrence of bile canalicular proliferation and portal fibrosis that rounded
      hepatic lobules. No well-defined nodules indicative of cirrhosis were seen. There
      was cholestasis with an increase in serum bilirubin, alkaline phosphatase and
      transaminase levels, and a decrease of albumin levels. Survival was 63.7%. Thirty
      days after biliary diversion (60 days after ligation) the normal lobular pattern
      was disorganized and regenerative nodules indicative of cirrhosis appeared,
      separated by narrow fibrous connective tissue septa, in 65% of rats. Bilirubin
      levels returned to normal values. Alkaline Phosphatase and transaminase levels
      remained high and albumin levels remained low. Overall survival was 25%.
      CONCLUSIONS: 30 days after biliary obstruction there are no regeneration nodules
      indicative of cirrhosis. There is a precirrhotic change, biliary fibrosis.
      Biliary diversion does not improve the histological changes and regeneration
      nodules and cirrhosis appear in 65% of animals.

PMID- 7727165
TI  - [Prognostic factors in severe acute pancreatitis. Univariate and multivariate
      study].
AB  - OBJECTIVES: The aim of this study was to analyze the prediction of mortality in
      patients with severe acute pancreatitis. PATIENTS AND METHODS: In a retrospective
      study 43 patients with severe acute pancreatitis were included. All patients
      required ICU admittance and surgical treatment. We evaluated severity according
      to Ranson's criteria, APACHE II score, CT scan classification (Hill),
      intraoperative findings (Vankemmel's classification) and number of organs
      failure. We performed a univariant and multivariant statistic study with lineal
      discriminant analysis. RESULTS: The overall mortality was 46.5%. Ranson's score
      and APACHE II did not correlate with mortality. Hill's classification did not
      reach significance either. However, only the Vankemmel's classification and the
      number of organs failure had statistic value (p < 0.01). After lineal
      discriminant analysis, the association of more than 4 Ranson's criteria, APACHE
      II up to 9 points, grades IV and V in Hill's classification and 4 organs failure
      had a predictive value for mortality. CONCLUSIONS: In our limited experience the
      Vankemmel's classification and the number of organs failure had a predictive
      value for mortality in patients with acute pancreatitis. The association of more
      than 4 Ranson's criteria. APACHE II up to 8 points, grades IV-V in Hill's
      classification and 4 organs failure disclosed poor prognosis.

PMID- 7727166
TI  - [Candida esophagitis and cytomegalovirus gastritis: optic and immunohistochemical
      diagnosis in an HIV+ patient].
AB  - Esophageal candidiasis, along with gastritis caused by cytomegalovirus--CMV--, is
      a common opportunistic infection in immunodepressed patients. A clinico
      pathological description is made of a human immunodeficiency virus-positive
      female (group IV-C-2) with a history of odynophagia and dysphagia resistant to
      treatment. The light microscopy and immunohistochemical study of an endoscopic
      esophago-gastric biopsy allowed the diagnosis of moniliasic esophagitis
      associated with CMV-induced gastritis. Emphasis is placed on the efficacy of
      immunohistochemical techniques over other methods in diagnosing CMV infection.

PMID- 7727167
TI  - [Perforation of small intestine diverticulum in Ehlers-Danlos syndrome].
AB  - We report a case of acute abdomen in a patient previously diagnosed of Ehlers
      Danlos syndrome. The pneumoperitoneum on the chest x-ray demanded urgent
      operative intervention. Laparotomy revealed two diverticula perforations in the
      small bowel. Perforation in the colon is common; however only two cases of small
      bowel perforation have been reported so far.

PMID- 7727168
TI  - [Gastric necrosis caused by acute gastric distention and superior mesenteric
      artery syndrome].
AB  - We report the case of a 14 year-old female patient who was admitted complaining
      of abdominal pain due to gastric distension after an episode of bulimia. The
      patient was diagnosed as having gastric intramural necrosis by CT. An emergency
      laparotomy was performed and a massive gastric necrosis and duodenal compression
      due to the superior mesenteric artery syndrome was found. The patient did well
      after total gastrectomy and Roux-en-Y procedure.

PMID- 7727169
TI  - [Solitary ulcer of the rectum and granulomatous appendicitis, a casual
      association?].
AB  - We report a case of solitary rectal ulcer (SRU) in a patient who had been
      previously diagnosed of granulomatous appendicitis. Both entities were
      histologically confirmed. The patient is asymptomatic after appendectomy done one
      and a half years ago, demonstrating the low recurrence rate of granulomatous
      appendicitis and the silent course of solitary rectal ulcer in many patients.
      Both entities may be related.

PMID- 7727170
TI  - [Retractile mesenteritis. Report of 3 cases].
AB  - Mesenteric panniculitis is an infrequent pathology; the diagnosis is made by the
      pathologist and it is characterized by inflammation, fibrosis and retraction of
      the mesenteric fat. We report three new cases of retractile mesenteritis or
      mesenteric panniculitis, two cases presented with intestinal obstruction and the
      other had an abdominal tumour. In all cases the pathological diagnosis was
      retractile mesenteritis.

PMID- 7727171
TI  - [Mixed cryoglobulinemia associated with hepatitis C virus].
AB  - We report six cases of essential mixed cryoglobulinemia associated with chronic
      liver disease and positive HCV markers, who showed several acute symptoms of
      vasculitis, arthralgias, neuropathy and glomerulonephritis. The presence in the
      serum and cryoprecipitates of anti HCV antibodies detected by the second
      generation ELISA (ELISA 2) and the of HCV RNA by PCR in the serum in all six
      cases, suggest an important role for this virus in the pathogenesis of mixed
      cryoglobulinemia.

PMID- 7727172
TI  - [Retroperitoneal tuberculous abscess].

PMID- 7727173
TI  - [Non-functioning neuroendocrine tumor of the pancreas].

PMID- 7727174
TI  - [Is there a relationship between digestive symptoms and H. pylori infection?].
AB  - Infection by H. pylori is a common finding in the general population, its
      prevalence being higher in certain gastroduodenal diseases, particularly peptic
      ulcer and chronic gastritis. There is no general agreement on whether there is an
      association between digestive symptoms and the presence of H. pylori infection.
      AIM: To study whether there is an association between digestive symptoms and H.
      pylori infection. METHODS: 328 patients with symptoms related to the upper
      gastrointestinal tract who underwent a diagnostic endoscopy were studied.
      Symptoms were classified as: epigastric pain, epigastric burning, heartburn,
      nausea or vomiting, and dyspeptic symptoms suggestive of motility disorders.
      During endoscopy 3 biopsy samples were obtained from both the gastric antrum and
      the body of the stomach. One of the samples from each location was processed for
      microbiology studies, the other two for histological studies. A patient was
      considered to be infected by H. pylori when the organism was detected by
      microbiology and/or histology in any of the locations. RESULTS: The mean age of
      patients was 47.3 + 15.2 years; the male/female ratio was 2.4/1. The endoscopic
      findings and the corresponding percentages of H. pylori infection were: normal
      endoscopy 55 (80%); gastritis 87 (82.7%); gastric ulcer 49 (100%); duodenal ulcer
      88 (100%); duodenitis 20 (95%); gastric cancer 7 (100%), and gastrectomy 22
      (71.4%). The frequency of the different clinical entities according to a positive
      or negative microbiological result was, respectively: epigastric pain
      (78.3/81.8%), epigastric burning (56.9/45.4%), heartburn (30.1/27.3%), nausea or
      vomiting (28.4/33.3%), and dyspeptic symptoms suggestive of motility disorders
      (53.8/54.5%); no significant differences were observed between the different
      groups. CONCLUSION: We found no association between digestive symptomatology and
      H. pylori infection, considering overall the most frequent gastrointestinal
      entities and the subgroup of patients with non-ulcer dyspepsia.

PMID- 7727175
TI  - Coronary surgery without cardiopulmonary bypass.

PMID- 7727176
TI  - Warm blood cardioplegia.

PMID- 7727177
TI  - Is increased tissue ferritin a risk factor for atherosclerosis and ischaemic
      heart disease?

PMID- 7727178
TI  - Preliminary report: genetic variation in the human stromelysin promoter is
      associated with progression of coronary atherosclerosis.
AB  - Stromelysin is a member of the family of metalloproteinases that degrade
      extracellular matrix. In situ hybridisation and histopathological studies suggest
      that stromelysin activity may be important in the connective tissue remodelling
      processes associated with atherogenesis and plaque rupture. Single strand
      conformation polymorphism analysis identified a common polymorphism in the
      stromelysin gene promoter located 1171 bp upstream from the start of
      transcription in which one allele has a run of six adenosines (6A) and another
      has five adenosines (5A). 72 men with coronary heart disease, were genotyped.
      They were participants in the St Thomas' Atherosclerosis Regression Study who
      were randomised to receive usual care (UC), dietary intervention (D), or diet
      plus cholestyramine (DC), with angiography at baseline and at 39 months. In these
      patients the frequency of the 5A allele was 0.49 (95% CI from 0.41 to 0.57) and
      was not significantly different from that in a sample of 354 healthy UK men. In
      the UC group, patients who were homozygous for the 6A allele showed greater
      progression of angiographic disease than those with other genotypes: the minimum
      absolute width of coronary segments decreased by 0.04 (SEM 0.10) mm for 5A5A,
      0.20 (0.07) mm for 5A6A, and 0.67 (0.19) mm for 6A6A (P < 0.01). The findings
      were similar but slightly less significant for the change in mean absolute width
      of coronary segments (P < 0.05). No significant associations were seen in
      patients in the D or DC groups. In data pooled from the three treatment groups,
      the 6A6A genotype was significantly associated with greater progression of
      coronary atherosclerosis than other genotypes in patients with baseline
      percentage diameter stenosis less than 20% (P < 0.05), but not in those with
      baseline percentage diameter stenosis greater than or equal to 20%. These results
      provide the first evidence of a link between genetic variation in stromelysin and
      progression of coronary atherosclerosis and support the hypothesis that
      connective tissue remodeling mediated by metalloproteinases contribute to the
      pathogenesis of atherosclerosis.

PMID- 7727179
TI  - Identification of patients at high risk for adverse coronary events while
      awaiting routine coronary angioplasty.
AB  - BACKGROUND: Identification of patients at risk for progression of coronary
      stenosis and adverse clinical events while awaiting coronary angioplasty is
      desirable. OBJECTIVE: To determine the standard clinical or angiographic
      variables, or both, present at initial angiography associated with the
      development of adverse coronary events (unstable angina, myocardial infarction,
      and angiographic total coronary occlusion) in patients awaiting routine
      percutaneous transluminal coronary angioplasty (PTCA). PATIENTS AND METHODS:
      Consecutive male patients on a waiting list for routine PTCA. Routine clinical
      details were obtained at initial angiography. Stenosis severity was measured
      using computerised angiography. OUTCOME MEASURES: Development of one or more of
      myocardial infarction, unstable angina, or angiographic total coronary occlusion
      while awaiting PTCA were recorded as an adverse event. RESULTS: Some 214 of 219
      patients underwent a second angiogram. One had a fatal myocardial infarction and
      four (2%) were lost to follow up. Fifty patients (23%) developed one or more
      adverse events (myocardial infarction five, unstable angina 35, total coronary
      occlusion 23) at a median (range) interval of 8 (3-25) months. Twenty (57%) of
      the 35 patients with unstable angina developed adverse events compared with 30
      (17%) of the 180 with stable angina (P = 0.0001). Plasma triglyceride
      concentration was 2.6 (1.2) mmol/l in patients with adverse coronary events
      compared with 2.2 (1.1) mmol/l in those without such events (P < 0.05). Patients
      with adverse events were younger than those without (54 (9) years v 58 (9) years,
      P < 0.01). The relative risk of an adverse event in patients with unstable angina
      and increased plasma triglyceride concentrations was 6.9 compared with those
      presenting with stable angina and a normal triglyceride concentration (P < 0.02).
      CONCLUSIONS: The study shows that adverse events are not uncommon in patients
      awaiting PTCA. Patients at high risk for adverse events may be predicted by the
      presence of acute coronary syndrome, increased concentration of plasma
      triglyceride, and younger age at the time of the first angiogram.

PMID- 7727180
TI  - Transient release of lipid peroxidation products as a non-invasive marker of
      successful reperfusion after thrombolysis for myocardial infarction.
AB  - OBJECTIVES: To evaluate an increase in plasma concentration of thiobarbituric
      acid reactive substances as a non-invasive biochemical test of reperfusion after
      thrombolysis and to investigate the relation between the inflammatory response
      after acute myocardial infarction and the production of the substances. METHODS:
      Venous samples were taken from 19 patients receiving thrombolysis for acute
      myocardial infarction before the start of therapy and every hour afterwards up to
      5 hours and then at 24 and 48 hours and the concentration of thiobarbituric acid
      reactive substances measured. These substances are markers of lipid peroxidation
      induced by free oxygen radicals. Early reperfusion was judged by regression of ST
      elevation and late coronary artery patency from the results of coronary
      angiography 24-72 hours after thrombolysis. RESULTS: The concentration of
      thiobarbituric acid reactive substances increased in only 6 out of 14 patients
      with signs of early reperfusion. In patients with late coronary artery patency
      the corresponding number was 6 out of 15. However, a significant increase in the
      concentration of thiobarbituric acid reactive substances was found for the whole
      group 24 and 48 hours after treatment. The change in concentration in serum
      correlated significantly with that of C reactive protein--an acute phase reactant
      (r = 0.62, P < 0.01)--but not to the serum activities of markers of infarct size
      such as creatine kinase B and lactate dehydrogenase. CONCLUSIONS: The
      fluorimetric assay used in this study to measure the concentration of
      thiobarbituric acid reactive substances seems to be an insensitive method of
      detecting reperfusion after thrombolysis for myocardial infarction. The increase
      in concentrations found 24 and 48 hours after treatment correlated with C
      reactive protein concentrations but not with those of markers of infarct size.

PMID- 7727181
TI  - Combining salicylate and enalapril in patients with coronary artery disease and
      heart failure.
AB  - OBJECTIVE: To study the effects of adding a salicylate to the angiotensin
      converting enzyme inhibitor enalapril in patients with heart failure due to
      coronary artery disease. DESIGN: Double blind, crossover study for three days in
      hospital followed by an extended similar study outside hospital over two months
      of once daily enalapril plus salicylate and enalapril plus placebo. SETTING:
      Tertiary referral centre. PATIENTS: 20 patients with heart failure due to
      myocardial infarction (New York Heart Association class II or III) and an
      ejection fraction less than 0.40. Twelve patients completed the two parts of the
      study. MAIN OUTCOME MEASURES: Blood pressure, plasma converting enzyme activity;
      plasma angiotensin II and noradrenaline concentrations; excretion of metabolites
      of renal and systemic prostanoids. RESULTS: The unloading effect of first and
      second dose of enalapril in the morning lasted only during the day; in the
      extended study it lasted 24 hours because of the drug's accumulation. Converting
      enzyme inhibitors attenuate the breakdown of bradykinin and therefore enhance
      prostaglandin E2 synthesis mediated by bradykinin. Evidence was found of such a
      prostaglandin E2 mediated contribution to ventricular unloading by enalapril,
      which was blocked by salicylate. The contribution, however, was small and
      variable, and salicylate addition had on average no significant de-unloading
      effect during the day. Unloading was abolished in only three of the 20 patients
      in the short term study and in one of the 12 in the extended study. At night,
      when other effects of enalapril on blood pressure had waned and the bradykinin
      induced effect persisted, salicylate significantly reduced the remaining small
      unloading effect. No effect was seen of salicylate addition on reversal of
      remodelling. Enalapril reduced angiotensin II induced synthesis of systemic and
      renal prostaglandin I2 and thromboxane A2, initially only during the day, but
      later also at night. It thereby masked suppression of thromboxane A2 synthesis by
      salicylate, which is the effect to which reinfarct prevention by salicylate is
      attributed. CONCLUSION: The risk is low that salicylate will substantially reduce
      the benefit of enalapril in patients with heart failure by de-unloading the
      ventricle. Like other effects induced by bradykinin significant de-unloading
      occurs in only a minority of the patients. In the presence of enalapril, however,
      salicylate will probably not be as effective as expected in reducing reinfarction
      risk, because enalapril already reduces thromboxane A2 synthesis effectively in
      patients with heart failure and no further reduction by salicylate was found.

PMID- 7727182
TI  - Leiomyosarcoma in the right atrium and occluding the inferior vena cava.

PMID- 7727183
TI  - Effects of captopril and oxygen on sleep apnoea in patients with mild to moderate
      congestive cardiac failure.
AB  - OBJECTIVES: To determine the effects of captopril and oxygen on sleep quality in
      patients with mild to moderate cardiac failure. DESIGN: An open observational
      study. PATIENTS: 12 patients with New York Heart Association class II-III heart
      failure were studied at baseline. 9 of these patients were then examined at the
      end of 1 month of treatment with captopril; 9 of the patients were separately
      assessed during a single night of supplementary oxygen. MAIN OUTCOME MEASURES:
      Sleep patterns by polysomnography, overnight oximetry, and subjective sleep
      assessment using visual analogue scores. RESULTS: Abnormal sleep was present in
      all baseline studies. Complete polysomnograms after treatment with captopril were
      obtained in 8 patients. Light sleep (stages 1 and 2) was reduced (mean (SEM)
      61%(8)% to 48%(6)% actual sleep time, P < 0.05) but slow wave (stages 3 and 4)
      and REM (rapid eye movement) sleep increased (25%(6)% to 31%(5)%, 14%(2)% to
      21%(5)% actual sleep time, P < 0.05). Apnoeic episodes (242(59) to 118(30), P <
      0.05), desaturation events (171(60) to 73(37), P < 0.05), and arousals (33(5) to
      18(3) P < 0.01) were reduced. Visual analogue scores of sleep quality increased
      49(5) to 69(5), P < 0.01). Complete polysomnograms were obtained in 7 patients
      treated with oxygen. Light sleep duration was reduced (55% (7)% to 42%(5)% actual
      sleep time, P < 0.05) and slow wave sleep increased (30%(5)% to 38%(6)% actual
      sleep time, P < 0.05). REM sleep duration was not significantly different. Total
      arousals (33(6)% to 20(2) P < 0.05), desaturation events (140(33) to 38(10), P <
      0.01), and apnoeic episodes (212(53) to 157(33), P < 0.05) were reduced. Visual
      analogue scores of sleep quality were unchanged. CONCLUSIONS: Captopril and
      oxygen may improve sleep quality and reduce nocturnal desaturation in patients
      with mild to moderate cardiac failure. Improved sleep quality could explain the
      reduction in daytime symptoms seen after treatment in patients with chronic heart
      failure.

PMID- 7727185
TI  - Radiofrequency catheter ablation of Mahaim tachycardia by targeting Mahaim
      potentials at the tricuspid annulus.
AB  - BACKGROUND: Reentrant tachycardias associated with Mahaim pathways are rare but
      potentially troublesome. Various electrophysiological substrates have been
      postulated and catheter ablation at several sites has been described. OBJECTIVE:
      To assess the efficacy and feasibility of targeting discrete Mahaim potentials
      recorded on the tricuspid annulus for the delivery of radiofrequency energy in
      the treatment of Mahaim tachycardia. PATIENTS: 21 patients out of a consecutive
      series of 579 patients referred to one of three tertiary centres for catheter
      ablation of accessory pathways causing tachycardia. All had symptoms and
      presented with tachycardia of left bundle branch block configuration or had this
      induced at electrophysiological study. In all cases, the tachycardia was
      antidromic with anterograde conduction over a Mahaim pathway. RESULTS: 6 patients
      had additional tachycardia substrates (4 had accessory atrioventricular
      connections and 2 had dual atrioventricular nodal pathways and atrioventricular
      nodal reentry). After ablation of the additional pathways, Mahaim potentials were
      identified in 16 (76%) associated with early activation of the distal right
      bundle branch and radiofrequency energy at this site on the tricuspid annulus
      abolished Mahaim conduction in all 16 cases. In 2 patients there was early
      ventricular activation at the annulus without a Mahaim potential but
      radiofrequency energy abolished pre-excitation. In the remaining patients no
      potential could be found (1 patient), no tachycardia could be induced after
      ablation of an additional pathway (1 patient), or no Mahaim conduction was
      evident during the study (1 patient). During follow up (1-29 months (median 9
      months)) all but 1 patient remained symptom free without medication. CONCLUSIONS:
      Additional accessory pathways seem to be common in patients with Mahaim
      tachycardias. The identification of Mahaim potentials at the tricuspid annulus
      confirms that most of these pathways are in the right free wall and permits their
      successful ablation and the abolition of associated tachycardia.

PMID- 7727184
TI  - Pathophysiology and time course of silent myocardial ischaemia during mental
      stress: clinical, anatomical, and physiological correlates.
AB  - OBJECTIVE: To define the prevalence and pathophysiology of myocardial ischaemia
      induced by mental stress in patients with coronary artery disease and exercise
      inducible ischaemia, and to determine the correlation between the severity of
      coronary artery disease and ischaemia induced by speech. DESIGN: Prospective
      cohort study. SETTING: Tertiary care academic institution. PATIENTS AND PROTOCOL:
      47 patients with coronary artery disease and 20 normal controls were studied
      using standardised exercise and mental stress. The ambulatory nuclear vest
      provided continuous measures of left ventricular ejection fraction and relative
      volume changes: an ischaemic response to mental stress was defined as a decrease
      in ejection fraction of > or = 5% for > or = 60 s. Severity of coronary artery
      disease was assessed by the extent of thallium reversibility on exercise testing
      and the severity of angiographic disease. RESULTS: 23 (49%) of 47 patients with
      coronary artery disease had an ischaemic response to mental stress which occurred
      early, was sustained throughout the task and associated with an increase in end
      systolic volume. In contrast, the pattern of left ventricular response in the
      remaining 24 patients (51%) resembled that in the normal controls. Patients with
      mental stress induced ischaemia tended to have greater severity of coronary
      disease (mean (SD) total number of diseased vessels 1.9 (0.8) v 1.4 (0.9), P =
      0.07), more frequent exercise induced angina (17/23 v 7/24, P = 0.003) and lower
      increases in heart rate (36 (11) v 49 (23) beats per min, P = 0.023) and systolic
      blood pressure (32 (19) v 45 (18) mm Hg, P = 0.03) during exercise. Left
      ventricular responses to speech and exercise were compared in the 23 patients
      with mental stress induced ischaemia: mental stress was associated with a greater
      decrease in ejection fraction at comparable increases in rate pressure product (
      6.5 (6.3)% v 4.7 (11.2)%, P = 0.0001). CONCLUSIONS: These findings suggest that
      mental stress induction of myocardial ischaemia is common in patients with stable
      coronary artery disease. Susceptible patients may have more functionally severe
      coronary disease. The time course, pattern, and haemodynamic features of mental
      stress induced ischaemia suggest a dynamic decrease in coronary supply.

PMID- 7727187
TI  - Effect of exercise on cycle length in atrial flutter.
AB  - OBJECTIVE: To examine the effect of exercise on cycle length in atrial flutter.
      PATIENTS: 15 patients with chronic atrial flutter. Seven patients were taking
      digoxin and six verapamil; two were not taking medication. METHODS: All patients
      underwent bicycle ergometry. Flutter cycle length was measured at rest and at
      peak exercise. RESULTS: Mean flutter cycle length increased from 245 ms to 256 ms
      (P = 0.002). Six patients developed 1:1 atrioventricular conduction. Significant
      increases in flutter cycle length were observed irrespective of development of
      1:1 atrioventricular conduction and use of digoxin and verapamil. CONCLUSION:
      Exercise prolongs flutter cycle length. This effect would promote development of
      1:1 atrioventricular conduction during exercise, causing inordinately high
      ventricular rates.

PMID- 7727186
TI  - Impaired left ventricular filling in hypertensive left ventricular hypertrophy as
      a marker of the presence of an arrhythmogenic substrate.
AB  - OBJECTIVE: To assess the prevalence of ventricular late potentials and
      ventricular tachycardia in hypertensive subjects with left ventricular
      hypertrophy and to study their relation to clinical characteristics. SETTING:
      Teaching and general hospital in Padua. METHODS: 107 hypertensive subjects with
      echocardiographic signs of left ventricular hypertrophy were studied with signal
      averaged electrocardiography and 24 hour Holter monitoring. Signal averaged
      electrocardiogram analysis was performed with high pass filters of 25 Hz, 40 Hz,
      and 80 Hz. Ventricular late potentials were considered to be present if at least
      two determinants of the signal averaged electrocardiogram were abnormal in one of
      the three filters. 70 normotensive subjects served as age matched controls.
      RESULTS: 25% (27) of the hypertensive subjects and 6% (four) of the controls
      showed late potentials on signal averaged electrocardiography (P < 0.0001). The
      hypertensive subjects with late potentials had a higher prevalence of ventricular
      tachycardia (33%, 9/27) than those without late potentials (13%, 10/80; P =
      0.035). Twenty nine per cent (31/107) of the hypertensive subjects had an
      inversion of the early to atrial filling velocity (E/A ratio < 1) on Doppler
      analysis of transmitral flow. Within this group the percentage of subjects with
      late potentials (55%, 17/31) and ventricular tachycardia (42%, 13/31) was much
      greater than that within the group of subjects without an inverted E/A ratio
      (13%, 10/76 (P < 0.0001) and 12%, 9/76 (P = 0.001) respectively). In a
      multivariate analysis only the E/A ratio was related to the presence or absence
      of either late potentials (P = 0.0001) or ventricular tachycardia (P = 0.0008).
      Both late potentials and ventricular tachycardia were unrelated to left
      ventricular mass, geometry, and systolic performance. CONCLUSIONS: A relation was
      found between the occurrence of ventricular tachycardia and the presence of late
      potentials in hypertensive subjects with left ventricular hypertrophy. Impaired
      left ventricular filling was the main marker for the arrhythmogenic substrate
      present in this disease.

PMID- 7727188
TI  - Aortic distensibility and stiffness index measured by magnetic resonance imaging
      in patients with Marfan's syndrome.
AB  - OBJECTIVES: To use magnetic resonance imaging to measure the elastic properties
      of the aorta of adults with Marfan's syndrome and to compare these results with
      those obtained by echocardiography. PATIENTS AND METHODS: 12 patients with
      Marfan's syndrome and 12 controls matched for age. Transverse luminal areas of
      the ascending and descending aorta were measured using electrocardiographic gated
      magnetic resonance imaging. Echocardiography was used to measure the diameter of
      the ascending aorta and aortic arch in patients with Marfan's syndrome. Blood
      pressure was measured during both scans. RESULTS: In diastole, transverse luminal
      areas of the ascending and descending aorta were significantly greater in
      patients with Marfan's syndrome when measured by magnetic resonance imaging and
      corrected for body surface area; P < 0.02 and P < 0.05 respectively. Patients
      with Marfan's syndrome had a higher stiffness index (112.77 v 5.78, P < 0.05) and
      a lower distensibility (0.0066 v 0.0105, P < 0.05) than controls. Results
      produced by MRI and echocardiography were not significantly different.
      CONCLUSIONS: Magnetic resonance imaging gives good quality reproducible images of
      the ascending and descending aorta. In patients with Marfan's syndrome, aortic
      distensibility and stiffness index measured by magnetic resonance imaging were
      abnormal (but did not always relate directly to the size of the aorta.

PMID- 7727189
TI  - Arm-ankle systolic blood pressure difference at rest and after exercise in the
      assessment of aortic coarctation.
AB  - OBJECTIVE: To evaluate the difference in systolic blood pressure at the arm and
      ankle at rest and after various exercise tests for the assessment of aortic
      coarctation. METHODS: 22 patients (mean age 33 years, range 17-66) were
      investigated on the suspicion of having haemodynamically significant aortic
      coarctation. Eight had undergone previous coarctation surgery, of whom five had
      received vascular grafts and three end to end anastomoses. The patients exercised
      submaximally while supine, seated on a bicycle, and walking on a treadmill, as
      well as exercising maximally on a treadmill. Arm and ankle blood pressure were
      measured with a cuff at rest and 1-10 minutes after exercise. Invasive pressures
      and cardiac output by thermodilution were recorded during catheterisation while
      patients were at rest and during and after supine bicycle exercise. The degree of
      constriction was assessed by angiography. Twelve healthy volunteers (mean age 32
      years, range 17-56) provided reference values for cuff pressures after exercise.
      RESULTS: All patients with a difference in cuff pressure at rest of 35 mm Hg or
      more had a difference in invasive pressure of 35 mm Hg or more. Increasing
      severity of constriction on angiography correlated with larger pressure gradients
      at rest and during exercise (P < 0.0001). When cuff measurements after exercise
      were considered singly or combined to form a predictor they did not improve the
      prediction of the invasive pressure gradients at rest or after maximal exercise.
      A pressure gradient between arm and ankle also developed in normal subjects after
      maximal but not after submaximal exercise. CONCLUSION: In most patients with
      suspected haemodynamically significant coarctation the difference in cuff
      pressure between arm and ankle at rest is sufficient to select patients in need
      of further evaluation. If exercise is performed submaximal exercise is
      preferable.

PMID- 7727190
TI  - Nutritional status of children with congenital heart disease.
AB  - OBJECTIVE: To assess the nutritional status of children with congenital heart
      disease. DESIGN: Six anthropometric, 24 biochemical, and five haematological
      markers of nutritional wellbeing were measured in children with congenital heart
      disease. SETTING: The west of Scotland. PATIENTS: 48 children admitted
      consecutively for surgical correction of congenital heart disease. MAIN OUTCOME
      MEASURES: Height, weight, and triceps and subscapular skin fold thicknesses were
      considered abnormal if they were below the third centile compared with standard
      reference data for age matched British children. Mid-arm circumference and arm
      muscle circumference were considered abnormal if they fell below the fifth
      centile compared with standard data. Biochemical and haematological data were
      compared with age matched and locally validated laboratory normals. RESULTS: A
      marked degree of undernutrition was evident in all children; 52% had weight less
      than the third centile, 37% were below the third centile for height, and 12.5%
      were below the third centile for triceps skin fold thickness and 18.8% for
      subscapular skin fold thickness. Mid-arm circumference and arm muscle
      circumference were below the fifth centile in 20.1% and 16.7% of children
      respectively. Five or more of the 29 biochemical and haematological measurements
      were abnormal in 83.3% of patients; 10 or more were abnormal in 12.5% of
      patients. CONCLUSIONS: Children with congenital heart disease are frequently
      undernourished, irrespective of the nature of cardiac defect and the presence or
      absence of cyanosis.

PMID- 7727191
TI  - Endomyocardial fibrosis in Egypt: an illustrated review.
AB  - The detailed features of right sided endomyocardial fibrosis are described in 15
      out of 10,000 consecutive patients who all had infection with Schistosoma mansoni
      and came from rural Egypt. Laboratory investigations, 12 lead
      electrocardiography, chest radiography, and Doppler echocardiography were
      performed in all patients. Cardiac catheterisation and angiography were performed
      in eight. Endomyocardial biopsy specimens were obtained from the right ventricles
      of two patients and pericardial biopsy specimens from two. Pericardiocentesis was
      performed in all patients. All patients were infected with S mansoni and had
      schistosomal hepatic fibrosis and ascites. Eleven had splenomegaly. All patients
      had raised cervical venous pressure with prominent Y descent and atrial
      fibrillation. Eosinophilia was notably absent. Echocardiography showed apical
      fibrosis in the right ventricle, obliteration of the ventricle, and moderate to
      massive exudative pericardial effusion in all patients. Calcification and
      fibrosis extended into the right ventricular outflow tracts in two patients. Huge
      right atrial thrombi occurred in five patients. Tricuspid regurgitation (grades I
      II) was detected in 11 patients by Doppler ultrasonography. Haemodynamic and
      angiographic data confirmed the pure right sided restrictive pathophysiology.
      Pericardial biopsy specimens showed perivascular inflammatory infiltrates in two
      patients and a schistosomal granuloma in one. Endocardial biopsy specimens showed
      dense fibrosis with many fibroblasts. Endomyocardial fibrosis in Egypt is unique
      in several aspects. It always affected only the right side of the heart.
      Calcification and fibrosis extended to the right ventricular outflow tract.
      Pericardial inflammatory reaction was present. The relation to schistosomiasis
      and the link to periportal hepatic fibrosis in these patients is intriguing.

PMID- 7727192
TI  - Twenty four hour continuous non-invasive finger blood pressure monitoring: a
      novel approach to the evaluation of treatment in patients with autonomic failure.
AB  - Occasional sphygmomanometric readings are not an effective way of evaluating the
      effect of treatment in patients with hypoadrenergic orthostatic hypotension. A
      novel non-invasive portable device (Portapres) was used to monitor 24 hour
      continuous finger blood pressure before and during chronic volume expansion in a
      66 year old woman with severe orthostatic hypotension. In both conditions
      pressures while she was standing were lowest in the morning. Her tolerance to
      standing and walking increased during the day and, as a consequence of a higher
      upright mean blood pressure, was improved after treatment. Mean blood pressure
      during sleep was increased after treatment. Continuous 24 hour non-invasive
      finger blood pressure monitoring is a promising technique for the evaluation of
      the effect of treatment in patients with autonomic failure. It provides
      information about situations in daily life that cannot be obtained by laboratory
      tests or conventional sphygmomanometric measurements.

PMID- 7727194
TI  - President's message: survey says....

PMID- 7727195
TI  - Stop, look, listen.

PMID- 7727193
TI  - Comparison of Doppler echocardiographic methods with heart catheterisation in
      assessing aortic valve area in 100 patients with aortic stenosis.
AB  - OBJECTIVE: To examine the practicability and accuracy of Doppler
      echocardiographic methods in determining aortic valve area. METHODS: Aortic valve
      areas determined by three methods using Doppler echocardiography (applying the
      continuity equation and the modified Gorlin formula using data from Doppler
      echocardiography and right heart catheterisation) were compared with values
      obtained by heart catheterisation. PATIENTS: 100 consecutive patients with aortic
      stenosis aged between 34 and 83 years (mean (SD) 66 (10)). RESULTS: Differences
      in individual patients' measurements of aortic valve area by the three Doppler
      techniques varied by up to 0.56 cm2 compared with values obtained by heart
      catheterisation. On average, values obtained from Doppler echocardiographic
      methods lay up to 51% below and 78% above those obtained by heart
      catheterisation. CONCLUSIONS: All three Doppler echocardiographic methods were
      practicable in routine clinical practice for patients of all ages, but they were
      of limited accuracy when compared with the aortic valve areas found invasively
      using the invasive Gorlin equation. However, these deviations may not always be
      due to inadequacies of the Doppler methods: they could also be caused by
      limitations in the Gorlin formula. Doppler methods can be repeated if required,
      they allow examination of the morphology of the valve, and they subject the
      patient to considerably fewer risks than the invasive procedure. An adequate
      strategy in determining the severity of aortic valve stenosis would be to
      calculate the valve area by Doppler echocardiography as well as considering the
      valvar aortic pressure gradient. The valve area alone should not be relied on
      exclusively, as has been the increasing practice in the past few years.

PMID- 7727196
TI  - Cyclosporine: a new therapeutic option for severe, recalcitrant psoriasis.
AB  - Severe, recalcitrant psoriasis can be a physically, emotionally, and socially
      debilitating disease. Cyclosporine is an important new option for the systemic
      treatment of this dermatologic disorder. Cyclosporine, an immunosuppressive agent
      used in the field of organ transplantation for more than a decade, has
      demonstrated marked efficacy in treating severe, recalcitrant psoriasis. However,
      its successful use requires patient education and careful, ongoing patient
      monitoring.

PMID- 7727197
TI  - What's your assessment? Nail changes.

PMID- 7727198
TI  - Clinical practice guidelines: implications for use.
AB  - The differences between standards and clinical practice guidelines are discussed.
      Implications for using guidelines in nursing practice in defining scope of
      practice, evaluating careless or negligent practice, practicing outside of
      clinical guidelines, and using clinical guidelines for cost containment are
      presented.

PMID- 7727199
TI  - DNA. Dermatology nursing scope of practice and dermatology nursing standards of
      clinical nursing practice. Standards and Certification Committee.

PMID- 7727200
TI  - Lymphomatoid papulosis: a model of lymphomagenesis.
AB  - Lymphomatoid papulosis (LyP) is a paradoxical cutaneous lymphoproliferative
      disorder. Clinically, it resembles the lesions of pityriasis lichenoides and
      behaves in a benign fashion in most patients. Histologically, it can mimic either
      Hodgkin's disease because of the presence of large atypical cells resembling Reed
      Sternberg cells (type A LyP) or cutaneous T-cell lymphoma because of the presence
      of cerebriform lymphocytes (type B LyP). A review of this uncommon skin disease
      is presented here.

PMID- 7727201
TI  - [Cytokine mediators in acute inflammation and chronic course of viral hepatitis].
AB  - Cytokines constitute a complex network of molecules involved in the regulation of
      the inflammatory response and the homeostasis of organ functions. Cytokines
      coordinate physiologic and pathologic processes going on in the liver, such as
      liver growth and regeneration, inflammatory processes including viral liver
      disease, liver fibrosis and cirrhosis. Liver growth and regeneration are
      regulated by several cytokines. The platelet-derived hepatocyte growth factor, in
      particular, delivers a strong mitogenic stimulus for hepatocyte regeneration. The
      cell-mediated immune response plays a central role in hepatocellular necrosis and
      in the immunopathogenetic mechanisms involved in viral clearance and persistence
      in liver disease of viral etiology. In this context, cytokines modulate the
      immune system and exert direct antiviral activity by cytopathic and non
      cytopathic mechanisms, as demonstrated in a transgenic mouse model. IL-6, TNF
      alpha, IL-1 and IL-2 increase in acute fulminant viral hepatitis; in fact, they
      have pro-inflammatory and cytotoxic effects. Reduced IL-2 and IFN-alpha synthesis
      and increased serum levels of IL-1 and IL-2 soluble receptor (IL-2R) have been
      observed in HBV chronic liver disease. In HCV chronic hepatitis, IL-2R increases
      as well, while IFN-gamma and IL-2 decrease. In personal experimental
      observations, intra-hepatic messenger RNA expression of several cytokines was
      measured in liver specimens of patients with chronic HBV and HCV infections:
      patients with HCV chronic liver disease had higher levels of IL-2, IL-6, IL-10,
      and IFN-gamma. These data are in accordance with immunological studies showing a
      vigorous cell-mediated immune response in HCV chronic liver disease and a
      deficient immune response in HBV chronic hepatitis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7727202
TI  - [Primary antiphospholipid antibody syndrome: clinical features and analysis of
      personal cases].
AB  - We studied 11 patients with primary antiphospholipid syndrome (PAPS), basing our
      diagnosis on Harris's clinical and serological criteria. Analysis of these cases
      brought to light a number of symptoms that have a statistically significant
      association with PAPS. Although these symptoms have not yet been recognized
      internationally as diagnostic criteria, we anticipate that they will be included
      on a revised and lengthened list of clinical symptoms used for the diagnosis of
      PAPS. There was a high incidence of neurological symptoms in our case group:
      disorders were often observed before the onset of full-blown disease and could be
      confirmed by means of cerebral NMR and SPECT analysis. We believe that further
      investigation will enable researchers to determine the predictive value of these
      PAPS-related neurological disorders.

PMID- 7727203
TI  - [Urinary infections in adults: clinical approach and therapeutic indications].
AB  - Urinary tract infections (UTI) are the most common of all the bacterial
      infections affecting humans during their life span. In adult patients, UTI may be
      categorized into the following groups: acute uncomplicated cystitis, acute
      uncomplicated pyelonephritis, recurrent bacterial UTI infections, asymptomatic
      bacteriuria, complicated UTI, acute and chronic bacterial prostatitis. In
      patients with uncomplicated cystitis, short-course (3 days) empirical therapy is
      more effective than single dose therapy. Recurrent cystitis can be effectively
      managed by continuous antimicrobial prophylaxis. Acute pyelonephritis in patients
      with anatomically normal urinary tracts should be treated with antimicrobial
      therapy for 10 to 14 days. Complicated infections require a full 10- to 14-day
      course of antimicrobial therapy. Urologic evaluation in patients with acute
      pyelonephritis or recurrent infections should not be routinely performed.
      Screening for asymptomatic bacteriuria is unnecessary in adults, except in
      particular circumstances. There is little evidence that UTI in adult patients
      lead to progressive chronic renal injury, unless complicating factors are
      concurrently present.

PMID- 7727205
TI  - [Centenarians: health status and life conditions].
AB  - The progressive lengthening of the average life span and the expanding elderly
      population high-light the phenomenon of "centenarianism" or extreme longevity in
      Italy. A large number of Italian Geriatric and Gerontology Centers throughout
      Italy have joined in the Italian Multicenter Study on Centenarians which
      evaluates the clinical and biological conditions of centenarians. A census of
      centenarians in Italy as of December 31, 1993 is presently in course. Preliminary
      data indicate that about 6000 subjects were alive on that day. Interesting
      epidemiological and biological information is also being processed. Scores based
      on the mini mental state, the index of independence in activities of daily
      living, the instrumental activities of daily living, and the geriatric depression
      scale, as well as laboratory tests, and case histories have evidenced a number of
      particular characteristics of centenarians: their longevity is familiar;
      centenarians live in a familiar and comfortable environment; they have been hard
      workers, and they have a good degree of mental self-sufficiency; they have never
      presented the classic risk factors, have always followed a balanced diet based on
      natural foods; they maintain a well-conserved immune system and especially
      natural killer activity; they have a normal lipidic balance and no symptomatic
      hyperglycemia. Mobility and morbidity rates are high. Further studies and
      interdisciplinary research should enable us to gain better understanding of the
      aging process and of life "over 100".

PMID- 7727204
TI  - [Functional changes of the endothelium and atherosclerotic process].
AB  - The aim of this review is to summarize the current concepts concerning the active
      role of the endothelium in the pathogenesis of atherosclerosis. Activated
      endothelium may promote the adhesion of monocytes and their transmigration into
      the intima. The coordinated expression of adhesion molecules of the selectin,
      integrin or immunoglobulin superfamily on the surface of endothelial cells and of
      monocytes modulates these events. The role of lipoproteins and their oxidative
      derivatives as well as that of selected cytokines and platelet activated factor
      in initiating changes on the endothelial cell surface has been investigated:
      these events are associated with an increased endothelial permeability to lipids
      and lipoproteins with their accumulation in the subendothelium. Once migrated
      into the intima, monocytes undergo morphological and functional modifications
      leading to the generation of a polypeptide mediator network which is instrumental
      in the migration, differentiation and proliferation of smooth muscle cells.
      Mediators produced by macrophages infiltrating the atherosclerotic plaque and by
      the endothelium may render the surface of the endothelial cells thrombogenic thus
      favoring thrombotic occlusion. In conclusion, the most recent studies suggest
      that the endothelium plays an active role in the pathogenesis of atherosclerosis.

PMID- 7727206
TI  - [Centenarians in Milan].
AB  - Demographic analysis of the populations in Italy has confirmed that the number of
      old people, particularly the very old, is progressively increasing. At present,
      92% of the women and 85% of the men reach the age of 60 years, and in 1990, there
      were 1660 centanarians in Italy. In this study we evaluated the demographic
      profile of the very old living in Milan. Data were collected by use of the Milan
      General Registry updated to January 1992. At that time there were 159
      centenarians and 166 persons over 100 years (range 101-106 years). Seventy-seven
      percent of the centenarians were females born in northern Italy who had been
      living in Milan for over 50 years. Of the subjects aged 101-106 years, 79% were
      women. One hundred twenty-five subjects were either widows or widowers, 82% had
      lived in Milan for over 50 years. Only 9% of the centenarians were
      institutionalized. Our survey confirms previous nationwide data obtained on
      centenarians indicating growth of the very old population.

PMID- 7727207
TI  - [The orthopedic-geriatric unit: a new model of hospital care].
AB  - We describe here the basic characteristics and operative modalities of the acute
      care orthopedic-geriatric unit, an innovative model of health care for elderly
      trauma patients. This new unit offers several advantages over traditional models:
      decreased patient mortality and length of hospital stay, a lower incidence of
      complications, and less need for specialist consultations. No particular
      organizational or management problems have arisen, and the cost/benefit ratio is
      very low. This model has also become a valuable teaching tool and a rich source
      of pathophysiological and clinical data for geriatric research.

PMID- 7727208
TI  - Central pontine myelinolysis: report of an asymptomatic case.
AB  - Central pontine myelinolysis (CPM), a disorder occurring for the most part in
      alcohol abusers, is characterized by the symmetric and selective destruction of
      medullated sheaths in the central pontine region. Detection of CPM in the pre
      symptomatic phase may improve the outcome, which is usually serious. We describe
      a case of CPM in a 48-year-old female alcohol abuser who was seen at our out
      patient clinic for a history of generalized seizures. Neurological examination
      was normal while magnetic resonance imaging revealed a pontine lesion consistent
      with CPM. On the basis of this report we hypothesize that the possibility to
      detect CPM in the pre-symptomatic phase will lead to increased diffusion of
      magnetic resonance imaging, and in turn to improved therapeutic strategies, such
      as the use of greater caution when correcting plasma electrolyte imbalance in
      alcoholics.

PMID- 7727209
TI  - [Diffuse symptomatic polypoid lipomatosis of the colon with hyperplasia of
      epiploic appendices: a case report].
AB  - Diffuse and symptomatic lipomatosis of the colon, particularly when associated
      with hyperplasia of the appendices epiploicae, is a rare disease. We report here
      the case of a lean, 26-year-old woman who had polypoid lipomatosis of the colon
      with submucosal and subserous expression (involving the mesentery and peritoneum)
      associated with extreme hyperplasia of the appendices epiploicae. Her disease led
      to a recurrent subocclusive syndrome which required total colectomy. We discuss
      the case and review the literature on this subject. The particular
      characteristics of this case and early onset of disease would suggest that our
      patient was affected by a congenital lipomatous syndrome linked to mesenchymal
      dysplasia. Long-term monitoring will enable prompt intervention in the case of
      reformation of lipomatous tissue.

PMID- 7727210
TI  - [A brief medical glossary].

PMID- 7727212
TI  - [Barrett's esophagus: current status].

PMID- 7727211
TI  - [Apoptosis or programmed cell death: regulatory and pathophysiological
      mechanisms].
AB  - Apoptosis is an active death process genetically encoded to eliminate abnormal or
      unwanted cells. The phenomenon is induced by a cascade of molecular events
      leading to nucleolysis by endonucleases and involves a number of membrane
      receptors and cytoplasmic proteins. These structures (including Fas, mullerian
      inhibiting substance, p53 and the c-myc oncogene) contribute, by interactive
      regulatory mechanisms, to the promotion or inhibition of apoptosis, on the basis
      of both external stimulus and cell activation state. Since apoptosis is a
      selective process to suppress defective cells, deregulation of genes encoding for
      such apoptosis-related proteins could be relevant in the growth of several
      tumors. Remarkably, overexpression of the bcl-2 gene in a few experimental
      lymphomas has been associated with neoplastic proliferation because of its
      inhibitory effect on apoptosis. Conversely, early activation of Fas, an apoptosis
      inducing gene on HIV-infected CD4+ lymphocytes, is thought to aggravate T cell
      lymphopenia in HIV infection by increasing the level of normal apoptosis. Genetic
      deregulation of apoptosis has also been postulated in the pathogenesis of several
      diseases. Indeed, while preliminary studies suggest that apoptosis plays a role
      in autoimmune disorders including systemic lupus erythematosus, the pathogenesis
      of a few degenerative neuropathies, such as Alzheimer's disease, could depend on
      a similar altered mechanism in apoptosis of neuronal cells. However, no studies
      are presently available to suggest that exploitation of molecular events of
      apoptosis would imply therapeutic progress.

PMID- 7727213
TI  - [Leiomyosarcoma of the inferior vena cava: description of a new case and review
      of the literature].
AB  - A case of primary leiomyosarcoma of the inter-renal vena cava is reported. This
      tumor is rare and up to date no more than 100 cases have been reported. Surgical
      treatment consisted in the removal of vena cava from the iliac veins to the
      suprahepatic veins with right nephrectomy. Restoration of vena cava and left
      renal vein continuity was not necessary because of the presence of collateral
      venous circulation at the time of operation. Venous ligation was haemodynamically
      well tolerated and the patient is disease-free at one year from operation.
      However, despite surgical radicality, prognosis remains poor given the frequency
      of metastases reported in more than 35% of cases.

PMID- 7727214
TI  - [Multimodal treatment of intrahepatic lithiasis with traditional surgery,
      endoscopy, and extracorporeal lithotripsy. Report of a clinical case].
AB  - A patient with residual intra-/extra-hepatic bile duct stones, previously
      admitted in emergency for acute necrotic pancreatitis and cholangitis, underwent
      the following procedures: 1) endoscopic sphincterotomy and naso-biliary tube
      drainage; 2) surgical operation (choledocholithotomy, operative choledochoscopy
      and T-tube external biliary drainage); 3) extracorporeal shock-wave lithotripsy;
      4) endoscopic sessions of fragmented stones removal. The above mentioned
      multimodal treatment, which resolved the intrahepatic lithiasis as shown 12
      months later by endoscopic retrograde cholangiography, is therefore suitable in
      order to avoid, at least initially, invasive radiologic or surgical procedures,
      i.e. transparenchymal approaches, intrahepatic derivations and hepatic
      resections.

PMID- 7727215
TI  - [Day surgery and one day surgery in pediatric surgery: personal experience].
AB  - The Authors report their experience with 738 children observed and operated for
      minor diseases in the period January 1989-June 1993. The children were
      hospitalized for day surgery or one day surgery. After some surgical,
      anaesthesiological, and postoperative pathophysiological considerations, and on
      the basis of their results (reduced local and general postoperative
      complications), the Authors confirm the benefit of this type of organization in
      terms of reduced nosocomial infections, reduced psychological traumas and
      increased socio-economic advantages.

PMID- 7727216
TI  - [Surgical repair of laparocele with expanded PTFE: technicalities].
AB  - Surgical repair of ventral hernias may often be quite difficult; however, the use
      of prosthesis, now generally accepted by many surgeons, has improved the results
      of such type of surgery. The Authors experience confirm the safety of the
      expanded PTFE and its versatility of employment, obtaining good functional and
      aesthetic results.

PMID- 7727217
TI  - [Thoracic lymphadenectomy in video-assisted mini-invasive thoracic surgery. First
      experience].
AB  - The Authors report their experience in the thoracoscopic surgical treatment of
      neurovascular abnormalities of the upper extremities. The experience acquired in
      the last two years with mini-invasive video-assisted thoracic surgery of the
      pleura and lung forced the Authors to perform thoracic sympathectomy following
      the same approach. In this way 4 thoracic sympathectomies were performed in 3
      patients. Two of them presented Raynaud's phenomenon, and one was affected by
      bilateral idiophatic upper limb hyperhidrosis. The operation is performed thanks
      to 3 12mm Thoracoports that allow the introduction of the telescope and operative
      instruments. It is easy to recognize and remove the sympathetic gangliar chain
      from T2 to T3. The short operative time required, the absence of mortality and
      morbidity, the regression of the symptomatology, the rapid return to work
      authorize to consider endoscopic transthoracic sympathectomy the gold standard in
      the treatment of neurovascular abnormalities of the upper extremities.

PMID- 7727218
TI  - [Indications and limitations of endoscopic sclerosis in esophageal varices: our
      current approach].
AB  - From January 1987 to December 1993, 171 patients affected by portal hypertension
      with bleeding complications underwent endoscopic variceal sclerotherapy. Results
      show that this technique is particularly effective for the hemostasis, therefore
      in high generic or specific risk patients is becoming a good alternative to
      traditional surgery.

PMID- 7727219
TI  - [Laparoscopic repair of bilateral and/or recurrent inguinal hernia].
AB  - The Authors report their three-year experience in the laparoscopic management of
      bilateral or recurrent hernia using a polypropylene mesh through a transabdominal
      extraperitoneal approach: out of a total of 500 laparoscopic hernioplasties
      performed, 162 patients with bilateral hernias and 51 with recurrent hernia
      underwent this procedure. In bilateral hernias a single wide patch was used to
      cover both the myopectineal foramen, therefore performing a Stoppa procedure by
      laparoscopy. Two major complications were registered in this series: 1 bleeding
      and 1 intestinal obstruction, both managed laparoscopically. Minor complications
      were: 2 cases of neuralgia and 6 seromas which required single or multiple
      evacuations. Patients were carefully followed up (1-31 months), and no relapses
      were recorded. Although the follow up is still too short, the Authors stress the
      characteristics of this technique which shows great advantages mainly represented
      by a good compliance, quick return to normal work and sport activity; in fact,
      recovery is obtained in a shorter period as compared to traditional surgery even
      when the latter includes the use of prosthetic mesh.

PMID- 7727220
TI  - [Acute cholecystitis: elements for diagnosis and therapy].
AB  - The Authors report their experience in the surgical management of 439 patients
      with acute cholecystitis. Symptoms and laboratory findings at onset, preoperative
      diagnostic tools, associated disorders, surgical procedures as well as age
      related postoperative morbidity and mortality and length of postoperative stay
      were analyzed. The most valuable investigation in the diagnosis of acute
      cholecystitis was ultrasound carried within the first 48 hrs, with positive
      results in 81% of cases. Tc-99m-HIDA biliary tract imaging proved to be a rapid,
      highly sensitive and specific, non invasive method of diagnosing acute
      cholecystitis in doubt cases. Morbidity (4.8%) and mortality (0%) rates in
      younger patients were inferior than those (22% vs 1.5%) observed in the elderly.
      Early and late results indicate that early cholecystectomy is the treatment of
      choice in acute cholecystitis.

PMID- 7727221
TI  - [Unusual location of hydatid cysts: clinical and therapeutic aspects].
AB  - Among patients treated for hydatidosis, unusual sites are observed in 5-30% of
      cases, with highest rates in endemic areas; on these basis during the diagnostic
      work up of masses arising from peritoneum, spleen, mediastinum, kidney and
      muscle, this possibility should be always taken into account. In fact, only a
      preoperative diagnosis allows a correct therapeutic approach, especially when
      synchronous lesions coexist. In this paper the Authors report their experience in
      the treatment of 66 (5.2%) hydatid cysts developed in unusual sites, out of 1275
      patients treated for hydatidosis from 1949 to 1993. They discuss the main
      pathogenetic and clinical features as well as the therapeutic management of these
      atypical lesions.

PMID- 7727222
TI  - Infection control: surveying the risks (continuing education credit).

PMID- 7727223
TI  - No smoking day. Starting stopping.

PMID- 7727224
TI  - Kissing it goodbye.

PMID- 7727225
TI  - Community care: redefining homesickness.

PMID- 7727226
TI  - Comparing methods of stoma formation.
AB  - Stoma care nurses have a key role in promoting discussion of anticipated problems
      and have a unique insight into the needs and difficulties of patients with
      temporary stomas. This article reviews the different management problems
      presented by temporary colostomies and ileostomies, and advocates a
      multidisciplinary approach to care.

PMID- 7727227
TI  - Clarifying outcomes in clinical practice.
AB  - The word 'outcome' is very much in vogue within today's healthcare system, yet
      its meaning varies between different levels of service, occupational groups and
      care environments. Using practical examples, this article aims to clarify the
      concept of outcome, and to explore some of the issues surrounding its use.

PMID- 7727228
TI  - Challenging behaviors (continuing education credit).

PMID- 7727229
TI  - Challenging beliefs about tuberculosis.
AB  - Tuberculosis (TB) is still prevalent in the UK, and current prevention strategies
      are largely reactive. This article describes a study of TB patterns in the Dudley
      area, the preliminary findings of which suggest that some commonly-held
      stereotypes about TB should be challenged. The author believes that if TB is to
      be eliminated from the UK, prevention strategies need to be proactive and based
      on locally determined needs. The clinical nurse specialist (TB) is ideally placed
      to lead this work.

PMID- 7727230
TI  - Right to nurse. Pay special: the case for fair pay.

PMID- 7727231
TI  - Right to nurse. Pay special: the bad old days.

PMID- 7727232
TI  - Right to nurse. Pay special: a bit excessive.

PMID- 7727233
TI  - Education: yes, or maybe no.

PMID- 7727234
TI  - Undervalued and underpaid.

PMID- 7727235
TI  - Ethics: moral objections.

PMID- 7727237
TI  - Pay special. Can nurses strike?

PMID- 7727236
TI  - Pay special. Yes, Prime Minister.

PMID- 7727238
TI  - Pay special. Winners and losers.

PMID- 7727239
TI  - Continence: a phone call away.

PMID- 7727240
TI  - Patient education in rheumatic disease.

PMID- 7727241
TI  - Managing people with dementia: CADE units.
AB  - In this, the last article in our series on caring for people with dementia in
      acute units, we depart from our accustomed format and offer an example of
      excellence in long-stay care. The author describes the philosophy and functioning
      of a CADE unit in Australia, which typifies what appropriate care of people with
      dementia is, and demonstrates how careful planning and thoughtful interventions
      can create an environment in which residents, family and staff can develop.

PMID- 7727242
TI  - Working on the bank: why do nurses do it?

PMID- 7727243
TI  - Computerised school health profiles: implementing a new system.
AB  - This paper describes the sequence of events from the instigation of a project
      pilot study, through the implementation of a district school nursing profile, to
      the results of a project which sought standardised information from school nurses
      on the health profiles in their schools. The profile form, which was introduced
      in 1992 and has been in regular use since, has allowed managers to gain accurate,
      easily accessible information on individual school health profiles, and to amend
      and adjust the workloads of school nurses accordingly.

PMID- 7727244
TI  - Right to nurse. A show of strength.

PMID- 7727245
TI  - Right to nurse. What the papers say.

PMID- 7727246
TI  - Media watch: the will to live.

PMID- 7727247
TI  - Pay: nothing to lose.

PMID- 7727248
TI  - Education: kan yu spel propply?

PMID- 7727249
TI  - Education: life in the shadow of the super-nurse.

PMID- 7727250
TI  - Concern over additions to HIV test programme.

PMID- 7727251
TI  - Read the small print.

PMID- 7727252
TI  - Trusts' offers vary around the country.

PMID- 7727253
TI  - Screening: giving the knowledge.

PMID- 7727254
TI  - The shape of time to come.

PMID- 7727255
TI  - Venous and leg ulcers (continuing education credit).

PMID- 7727256
TI  - Mental health. Long-stay service development: 'care'.
AB  - This is the first of two articles which describe the development of a new service
      for long-stay patients with chronic mental health problems. The first article
      highlights the theoretical and historical features of the project, and outlines
      the methods of the study. The second article examines the financial aspects of
      the project development, and draws conclusions from the data obtained.

PMID- 7727257
TI  - Disability and work: risk assessment.
AB  - Recent parliamentary debate has brought the rights of disabled people back into
      the spotlight of media attention. In the workplace, the occupational health nurse
      (OHN) is uniquely placed to make a positive contribution to the achievement of
      equal opportunities for people with disabilities. The author describes a risk
      assessment approach to the occupational health and safety of disabled persons and
      their employers. Such approaches can help to ensure that the work skills of all
      employees are used to maximum potential.

PMID- 7727258
TI  - Research: go on, prove it.

PMID- 7727259
TI  - Media: sick of getting a bad press.

PMID- 7727260
TI  - Learning disabilities: mixed feelings.

PMID- 7727261
TI  - Health education: send them packing.

PMID- 7727262
TI  - Cognitive style and personality in 12-year-old children.
AB  - Three hundred and eighty 12-year-old children were asked to rate the pupils in
      their class on seven personality characteristics (Humorous, Shy, Outgoing,
      Patient, Quiet, Lively, and Serious; part of the sample also rated two additional
      characteristics, Helpful and Sensible). They were also given the Cognitive Styles
      Analysis (CSA) (Riding, 1991a) which measures an individual's position on two
      fundamental cognitive style dimensions; Verbal-Imagery and Wholist-Analytic. A
      factor analysis indicated that the seven personality characteristics could be
      viewed as three variables; and these were labelled as Active, Modest and
      Responsible. Personality characteristic ratings varied significantly as a
      function of Verbal-Imagery Cognitive Style. Verbalisers were more Active than
      Imagers, the intermediate position of Bimodal were most Modest and the Imagers
      were more Responsible than the Verbalisers. There was also a significant gender
      difference with the girls being more Modest and Responsible and the boys more
      Active. For the subsample, the only significant effect that was observed related
      to gender with the girls being rated as more Helpful and more Sensible than the
      boys.

PMID- 7727263
TI  - Characteristics of ego- and task-oriented students: a comparison of two
      methodologies.
AB  - A motivation questionnaire was completely by 79 grade five students. Responses
      were subjected to a factor analysis which was followed by a series of Pearson
      correlations between the resultant factor scores and measures of ability
      perceptions, self-worth, self-efficacy, success and failure attributions,
      positive and negative emotions, and preference for challenge. Responses were also
      subjected to a cluster analysis followed by a series of between-group contrasts
      with each of the aforementioned motivational constructs as the dependent variable
      and cluster membership as the independent variable. Factor analytic-correlational
      methodology was compared to cluster analysis with between-groups contrasts to
      determine the agreement between the two methods. While there was agreement in
      interpretation of the data, several discrepancies appeared. The conclusion is
      that cluster analysis may be a useful way to refine goal theory.

PMID- 7727264
TI  - Burnout and coping among Chinese secondary school teachers in Hong Kong.
AB  - The tripartite components of burnout and eight coping strategies were assessed in
      a sample of 415 Chinese secondary school teachers in Hong Kong. While emotional
      exhaustion and depersonalisation were relatively undifferentiated among these
      teachers, a reduced sense of accomplishment as a distinct component of burnout
      was generally reported. The findings that avoidant coping strategies were
      consistently related to all three aspects of burnout suggested that teachers
      employing escape-avoidance to cope with stressors might be more prone to burnout.
      Implications for promoting certain patterns of coping to combat burnout were
      discussed.

PMID- 7727265
TI  - Conventional wisdom is a poor predictor of the relationship between discipline
      policy, student misbehaviour and teacher stress.
AB  - Will an effective discipline policy improve student misbehaviour and result in a
      reduction of teacher stress? It is commonly believed that student misbehaviour is
      a major cause of teacher stress, and that the degree of student misbehaviour is
      reflected in student suspension rates. Moreover, it is believed that student
      misbehaviour can be reduced by improving a school's discipline policy through the
      collaborative efforts of whole school communities. As a result of growing concern
      about student misbehaviour and teacher stress, a Whole School Approach to
      Discipline and Student Welfare programme was implemented throughout the
      Australian state of Victoria. This paper reports on the evaluation studies that
      were conducted to assess the effectiveness of the programme and examine the
      assumptions which underpinned its implementation. Data were obtained from 4,072
      primary and secondary school teachers. Although longitudinal analyses suggested
      that the programme was effective in reducing teacher stress, there was no mean
      change in student misbehaviour. Structural equation analyses showed that there
      was little relationship between a school's discipline policy and the perceived
      level of student misbehaviour. It was also found that student suspension rates
      were not related to student misbehaviour, but could be predicted on the basis of
      a school's discipline policy and the self-esteem of teachers. Two and three wave
      causal analyses also demonstrated the problems associated with using cross
      sectional research to support major policy decisions. Overall, these studies
      showed that there is little point in trying to reduce teacher stress by reducing
      student misbehaviour. Rather, it is more appropriate to develop a supportive
      organisational climate that enables teachers to cope with the student
      misbehaviour that confronts them.

PMID- 7727266
TI  - Symposium on teacher stress. Occupational stress among vocational teachers.
AB  - There is a widespread belief that work related stress among teachers is serious,
      with implications for teachers' health status and performance. The difficulty
      with interpreting data on teacher stress is that the measuring instruments used
      are often neither standardised nor sometimes focused on stressors pertinent to
      the occupational roles of teachers. This study, therefore, uses a recently
      developed test instrument called the Occupational Stress Inventory (OSI) which
      concisely measures occupational stress, strain and coping resources. Data were
      obtained, using the OSI, from a group of vocational teachers and compared to a
      group of professional non-teachers. Overall the results showed a significantly
      higher level of teacher stress, although only one of 10 stress and strain
      measures contributed to this effect. The implications for teachers, in terms of
      occupational role, are discussed.

PMID- 7727267
TI  - A structural model of the dimensions of teacher stress.
AB  - A comprehensive survey of teacher stress, job satisfaction and career commitment
      among 710 full-time primary school teachers was undertaken by Borg, Riding &
      Falzon (1991) in the Mediterranean islands of Malta and Gozo. A principal
      components analysis of a 20-item sources of teacher stress inventory had
      suggested four distinct dimensions which were labelled: Pupil Misbehaviour,
      Time/Resource Difficulties, Professional Recognition Needs, and Poor
      Relationships, respectively. To check on the validity of the Borg et al. factor
      solution, the group of 710 teachers was randomly split into two separate samples.
      Exploratory factor analysis was carried out on the data from Sample 1 (N = 335),
      while Sample 2 (N = 375) provided the cross-validational data for a LISREL
      confirmatory factor analysis. Results supported the proposed dimensionality of
      the sources of teacher stress (measurement model), along with evidence of an
      additional teacher stress factor (Workload). Consequently, structural modelling
      of the 'causal relationships' between the various latent variables and self
      reported stress was undertaken on the combined samples (N = 710). Although both
      non-recursive and recursive models incorporating Poor Colleague Relations as a
      mediating variable were tested for their goodness-of-fit, a simple regression
      model provided the most parsimonious fit to the empirical data, wherein Workload
      and Student Misbehaviour accounted for most of the variance in predicting
      teaching stress.

PMID- 7727268
TI  - Life at the chalkface--identifying and measuring teacher stress.

PMID- 7727269
TI  - The importance of self-efficacy as a mediating variable between learning
      environments and achievement.
AB  - The purpose of this research was to investigate the extent to which self-efficacy
      acts as a mediating variable between the learning environment and achievement.
      Seven year 5 classes (N = 179 students aged 9 to 10 years) were allocated
      randomly to cooperative, competitive or individualistic environments for twice
      weekly social studies lessons, changing environments after five weeks. Data
      collected on self-efficacy and achievement in weeks 5 and 10 indicated that co
      operative environments led to higher self-efficacy and achievement as well as
      more appropriate behaviour. The performance of particular tasks under competition
      appears to be enhanced when students have previously worked co-operatively, but
      may be difficult to sustain as self-efficacy and behaviour standards decline.

PMID- 7727270
TI  - Shyness and self-esteem in middle childhood.
AB  - The relationship between shyness and self-esteem was assessed for two samples of
      children aged 9 to 12 years. Shyness was measured by a new self-report
      questionnaire based on an elicitation of children's conceptions of shyness.
      Shyness was significantly correlated with measures of global self-esteem, with
      external locus of control and with perceived competence across different domains
      of the self. The relationship among variables were similar to those reported for
      adolescents and adults. Girls were more shy than boys, and there was a suggestion
      that 11-year-old children were more shy in secondary than in primary school.

PMID- 7727271
TI  - Spiroplasma velocicrescens sp. nov., from the vespid wasp Monobia quadridens.
AB  - Spiroplasma strain MQ-4T (T = type strain), which was isolated from the hemolymph
      of the vespid wasp Monobia quadridens, was serologically distinct from other
      spiroplasma species, groups, putative groups, and subgroups. Each strain MQ-4T
      cell was helical and motile and was surrounded by a single cytoplasmic membrane;
      there was no evidence of a cell wall. The strain grew well in 1% serum fraction
      medium, as well as in SM-1, M1D, and SP-4 liquid media, under both aerobic and
      anaerobic conditions. Strain MQ-4T grew at temperatures ranging from 10 to 41
      degrees C but did not grow at 43 degrees C. The strain grew optimally at 37
      degrees C with a doubling time of 0.6 h, the shortest doubling time recorded for
      any spiroplasma. Strain MQ-4T catabolized glucose and arginine but did not
      hydrolyze urea. The guanine-plus-cytosine content of the DNA was about 27.5 +/- 1
      mol%. The genome size was 1,480 kbp (940 MDa). Strain MQ-4 (= ATCC 35262) is
      designated the type strain of a new species, Spiroplasma velocicrescens.

PMID- 7727272
TI  - Random amplified polymorphic DNA fingerprinting of mosquito-pathogenic and
      nonpathogenic strains of Bacillus sphaericus.
AB  - Random amplified polymorphic DNA fingerprinting was used to examine 31 mosquito
      pathogenic and 14 nonpathogenic strains of Bacillus sphaericus. We verified that
      DNA bands that migrated the same distance in an agarose gel were homologous by
      using PCR-generated probes made from the random amplified polymorphic DNA bands.
      The band patterns obtained with eight primers were analyzed by using the Jaccard
      coefficient and unweighted pair group with arithmetic average clustering.
      Pathogenic strains belonging to DNA homology group IIA were similar to strains
      belonging to nonpathogenic homology groups at an average level of similarity of
      6.3%. Individual serotypes were clearly identified among the pathogenic strains.
      This suggests that there is overall genetic homogeneity among strains within
      serotypes. It is also consistent with the uniform toxicity pattern found for each
      serotype (unlike the toxin diversity found in Bacillus thuringiensis serotypes).
      These results, together with DNA homology data, support the proposal that a new
      species should be described for the pathogenic strains.

PMID- 7727273
TI  - Isolation and characterization of a thermophilic sulfate-reducing bacterium,
      Desulfotomaculum thermosapovorans sp. nov.
AB  - Strain MLFT (T = type strain), a new thermophilic, spore-forming sulfate-reducing
      bacterium, was characterized and was found to be phenotypically, genotypically,
      and phylogenetically related to the genus Desulfotomaculum. This organism was
      isolated from a butyrate enrichment culture that had been inoculated with a mixed
      compost containing rice hulls and peanut shells. The optimum temperature for
      growth was 50 degrees C. The G+C content of the DNA was 51.2 mol%. Strain MLFT
      incompletely oxidized pyruvate, butyrate, and butanol to acetate and presumably
      CO2. It used long-chain fatty acids and propanediols. We observed phenotypic and
      phylogenetic differences between strain MLFT and other thermophilic
      Desulfotomaculum species that also oxidize long-chain fatty acids. On the basis
      of our results, we propose that strain MLFT is a member of a new species,
      Desulfotomaculum thermosapovorans.

PMID- 7727274
TI  - Comparative ribosomal protein sequence analyses of a phylogenetically defined
      genus, Pseudomonas, and its relatives.
AB  - I analyzed various families of ribosomal proteins obtained from selected species
      belonging to the genus Pseudomonas sensu stricto and allied organisms which were
      previously classified in the genus Pseudomonas. Partial amino acid sequencing of
      L30 preparations revealed that the strains which I examined could be divided into
      three clusters. The first cluster, which was assigned to the genus Pseudomonas
      sensu stricto, included Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas
      mendocina, and Pseudomonas fluorescens. The second cluster included Burkholderia
      pickettii and Burkholderia plantarii. The third cluster, which was a deeply
      branching cluster in the stem of gram-negative bacteria, included Brevundimonas
      diminuta and Brevundimonas vesicularis. Despite the different levels of
      conservation of the N-terminal sequences of ribosomal protein families (the
      highest level of similarity was 74% for L27 proteins and the lowest level of
      similarity was 42% for L30 proteins), similar phylogenetic trees were constructed
      by using data obtained from sequence analyses of various ribosomal protein
      families, including the S20, S21, L27, L29, L31, L32, and L33 protein families.
      Thus, I demonstrated the efficacy of ribosomal protein analysis in bacterial
      taxonomy.

PMID- 7727275
TI  - A novel approach for discovering retrotransposons: characterization of a long
      terminal repeat element in the spoilage yeast Pichia membranaefaciens and its use
      in strain identification.
AB  - A novel PCR-based approach designed to detect retrotransposon long terminal
      repeat (LTR) elements via their association with tRNA genes was applied to Pichia
      membranaefaciens, an industrially important food spoilage yeast. A single primer
      based on tRNA gene sequences was used to amplify DNA fragments from different
      strains, and an observed fragment size difference among strains was found to
      correspond to the expected size of an integrated LTR. A 289-bp element was cloned
      as part of the larger fragment and shown to be present in a high copy number and
      variable genomic location in all strains examined. Sequence analysis revealed the
      element to be bounded by nucleotides TG at the 5' end and CA at the 3' end and to
      exhibit target site duplication and other sequence motifs diagnostic of
      retrotransposon LTRs. LTR sequence data enabled the development of a rapid
      identification method which distinguished among different strains. The novel
      method for LTR isolation and the strain identification system are both likely to
      prove generally applicable for a wide range of other organisms.

PMID- 7727276
TI  - DNA relatedness among Aeromonas allosaccharophila strains and DNA hybridization
      groups of the genus Aeromonas.
AB  - The genomic relatedness among three Aeromonas allosaccharophila strains,
      including the type strain, and other Aeromonas type and reference strains that
      were assigned to DNA hybridization groups was estimated by DNA-DNA hybridization
      (competition procedure using a membrane method). All A. allosaccharophila strains
      were highly related (70 to 100%) to strains 289T (= CECT 4199T) and ATCC 35942.
      Type strains of other validated Aeromonas species, reference strains of DNA
      groups 8 and 11, and the Aeromonas sp. strain ATCC 43946 (enteric group 501) were
      0 to 41% related to A. allosaccharophila 289T and ATCC 35942. The G+Cs content of
      A. allosaccharophila strains were in the range 55.9 to 57.3 mol%. The G+C content
      of the type strain of this species was 56.9 mol%, a value somewhat lower than
      that reported in the original description.

PMID- 7727277
TI  - Antibiotic susceptibility as a taxonomic characteristic of the genus Bacillus.
AB  - A large number of Bacillus strains assigned to different species were tested to
      determine their susceptibilities to antibiotics. Some clear differences between
      species were observed. The antibiotic susceptibilities of strains isolated from
      natural sources seemed to be stable and to reflect adaptation of the strains to
      specific conditions in certain ecological niches. A method for data processing
      which can be used for rapid species identification is described.

PMID- 7727278
TI  - Attenuation of ultraviolet radiation-induced edema and erythema with topical
      calmodulin and protein kinase C inhibitors.
AB  - We treated Skh:HR1 hairless albino mice, NSA mice and hairless albino guinea pigs
      topically with N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) or
      trifluoperazine (TFP) before or after ultraviolet (UV) irradiation. When applied
      before irradiation, W7 and TFP prevented edema in Skh-1 mice and W7 prevented UV
      induced edema in NSA mice in a dose-dependent manner. Preirradiation treatment
      with 2% W7 reduced erythema in guinea pigs by 50%. Epidermal histology of UVR
      treated Skh-1 mice pretreated with W7 before UVR was similar to unirradiated
      mice. W7 did not reverse or prevent these UV-induced effects when applied after
      irradiation. Neither TFP nor W7 absorbed UV based on forward scattering
      absorbance spectra; we conclude that neither are physical or chemical sunscreens.
      These results suggest that calmodulin and/or protein kinase C-dependent events
      are involved in manifesting some of the effects of UV irradiation on skin.

PMID- 7727279
TI  - Development and characterization of a novel skin model for cutaneous
      phototoxicology.
AB  - The biological consequences of exposure to ultraviolet radiation (UV) has been
      receiving increased attention. Most known biological effects (such as sunburn and
      skin cancer) are attributed to mid-wave UVB (290-320 nm) exposure. Phototoxicity,
      a nonimmunological UV-induced response, has been studied using in vivo (human and
      animal) and in vitro models. Ethical considerations and model limitations
      underscore the need for a reliable in vitro model to assess cutaneous
      phototoxicity that would ideally possess viable cells and have a normal
      anatomical structure with an intact and functional vasculature. This would allow
      therapeutic or preventive drugs to be tested in a system in which their
      disposition (cutaneous concentration-time profile) has been shown to be similar
      to the in vivo setting. In addition, morphological, biochemical and physiological
      changes should be easily monitored within the same system. The purpose of this
      study was to characterize the isolated perfused porcine skin flap (IPPSF)
      developed in our laboratory as a model for UVB exposure. IPPSFs (n > or =
      4/treatment) were irradiated with UVB doses of 1260 mJ/cm2, 630 mJ/cm2, 315
      mJ/cm2 or 0 mJ/cm2 both in vitro and in situ. Biomarkers used to assess
      phototoxicity demonstrated a decrease in glucose utilization, an increase in
      vascular resistance (pressure/flow) and an increase in the release of PGE2.
      Morphologically, intracellular and intercellular epidermal edema and sunburn
      (pyknotic) cells (SBC) increased with dose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727280
TI  - A double-blind study of cysteine photoprotection in erythropoietic
      protoporphyria.
AB  - In an open trial in 9 patients, we found that the ingestion of 500 mg of cysteine
      twice a day could prevent or lessen the photosensitivity associated with
      erythropoietic protoporphyria (EPP). We report here the results of a double-blind
      cross-over design trial in 16 patients. Patients with EPP were randomized into
      two groups, one that received 500 mg twice daily of cysteine during the first
      period and then placebo during the second period, and the second that received
      placebo first and then cysteine. Each drug ingestion period lasted 8 weeks, and
      there was a 1 week wash-out period between them. Patients were seen before the
      first period, at the end of the first period and at the end of the second period
      for phototesting, an objective method of assessing treatment efficacy, and for
      blood tests to monitor cysteine safety. The subjects also were asked to keep
      light-exposure diaries, a subjective method of assessing efficacy. We found that
      cysteine significantly prolonged the time it took to develop erythema by
      phototest, objectively demonstrating efficacy. In addition, analysis of patients'
      diaries showed that cysteine ingestion significantly increased the length of sun
      exposure it took to develop symptoms of photosensitivity. We conclude that
      cysteine ingestion may be an effective therapy in the prevention of
      photosensitivity associated with EPP.

PMID- 7727281
TI  - Minimum erythema dose determination in individuals of skin type V and VI with
      diffuse reflectance spectroscopy.
AB  - Erythema induced by ultraviolet B radiation (UVB) or PUVA (psoralen+UVA) was
      measured by diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry
      (LD) on patients receiving UV phototherapy and on healthy volunteers of skin type
      V and VI. The height of the 577 nm absorbance peak of oxyhemoglobin was taken as
      a measure of erythema intensity. DRS spectra from skin sites exposed to a series
      of doses were similar in shape. The dose necessary to produce a 0.05 difference
      in absorbance between 577 nm and 630 nm was determined to be a good indicator of
      minimal erythema dose (MED) in UVB. DRS measurements proved very reliable in the
      determination of MED or minimum phototoxic dose) of deeply pigmented subjects. In
      individuals with skin types V or VI, DRS detects and provides a measure for UVB
      and PUVA erythema and distinguishes it from melanin pigment, even when the
      erythema is not obvious. LD measurements lose sensitivity with increasing
      pigmentation and fail altogether in highly pigmented skin (types V and VI).
      Diffuse reflectance spectroscopic techniques also make possible the detection of
      sub-visual threshold reactions. DRS improved the accuracy of MED and MPD
      determination and the objective standardization of phototesting procedures
      irrespective of the subject's pigment level.

PMID- 7727282
TI  - Clinical and experimental photosensitivity reaction to tilisolol hydrochloride.
AB  - This report describes a patient who developed a photosensitivity reaction during
      the treatment of hypertension with tilisolol hydrochloride, which is a beta
      blocker agent Although the data are insufficient to distinguish photoallergy and
      phototoxicity, clinical and histologic features suggested that the mechanism
      involved was photoallergic in nature. The action spectrum was mainly the
      ultraviolet A range. The reaction was reproducible on oral readministration of
      the drug and exposure to a low dose of UVA. Photopatch testing with the drug was
      also positive only in the patient. Although the experimental photoallergic
      reaction was not induced in the guinea pig, phototoxic potential was demonstrated
      in the animal. To our knowledge, a photosensitivity reaction due to tilisolol
      hydrochloride has not been previously reported in the English literature.

PMID- 7727283
TI  - Photosensitivity reaction to methenamine hippurate. A case report.
AB  - We describe a 70-year-old woman who in the summer of 1992 presented at our
      department with an erythematous and blistering rash on the sun-exposed areas of
      her face, trunk and upper limbs. She had been taking methenamine hippurate for
      several years to prevent urinary tract infections after an cystopexia operation.
      Oral photoprovocation with the drug revealed an immediate reaction after 3 J of
      ultraviolet A not seen before oral photoprovocation.

PMID- 7727285
TI  - [Care of the premature in Kumamoto, Japan].

PMID- 7727284
TI  - Reproducible elevation of liver transaminases by topical 8-methoxypsoralen.
AB  - We present a case of a 17-year-old woman with vitiligo who had no known previous
      liver diseases nor any exposure to concurrent hepatotoxic drugs and who developed
      a liver injury while on topical methoxypsoralen photochemotherapy (PUVA). The
      reaction, manifested by elevated liver enzymes, was provoked on 3 consecutive
      occasions, and on the last one, with 1% methoxypsoralen lotion only. Although the
      exact mechanism of liver injury in our patient is unknown, it seems to be an
      idiosyncratic hypersensitivity reaction to topically applied methoxypsoralen.

PMID- 7727286
TI  - [The gentle care of prematures].

PMID- 7727287
TI  - [Caring for children with heart disease].

PMID- 7727288
TI  - [Kaiserin-Auguste-Victoria-Haus--an institution at the crossroads?].

PMID- 7727289
TI  - [Violence in family and school].

PMID- 7727291
TI  - [Safe keeping of money and valuables belonging to the patients in the hospital].

PMID- 7727290
TI  - [Questions of hygiene from the practice].

PMID- 7727292
TI  - [Designing of pediatric departments--considerations and experiences on the
      construction and restructuring of pediatric hospitals and departments].

PMID- 7727293
TI  - High standards of practice, education and research.

PMID- 7727294
TI  - Regina health district & management. Southern Saskatchewan Stroke Prevention
      Unit.

PMID- 7727295
TI  - AIDS dementia complex: guidelines for nursing care.
AB  - AIDS dementia complex is one of the most common neurological problems associated
      with HIV-related illness. To date, the nursing care of individual with AIDS
      dementia complex has not been explored to any extent. As a basis for examining
      aspects of nursing care, the epidemiology, neuropathology, clinical presentation
      and diagnosis of AIDS dementia complex are reviewed and medical management
      considered. Using the stages of AIDS dementia complex, guidelines for nursing
      care are proposed. These guidelines are a basis for developing individualized
      care to enhance the abilities of persons with AIDS dementia complex and to
      support caregivers.

PMID- 7727296
TI  - The impact of prevention.
AB  - The vision for nursing in Nova Scotia states "We value the worth, dignity and
      cultural diversity of people. We create mechanisms by which we can continually
      develop our fullest potential as individuals and as a profession." Networking
      with community groups to increase health awareness and promote prevention follows
      this vision. Does a prevention program have an impact on our community? S.C.I.P.
      Nova Scotia (Spinal Cord Injury Prevention) is a volunteer community based injury
      prevention program which is continually evolving. Based on epidemiological
      information this paper will discuss the evolution of our various prevention
      programs due to these statistics.

PMID- 7727297
TI  - Trials and tribulations: patients' perspectives of the Betaseron study.
AB  - The University of British Columbia Multiple Sclerosis (MS) Clinic was one of 11
      North American sites involved in the double-blind, placebo-controlled phase III
      trial of Betaseron in relapsing-remitting MS. UBC participants as a unique sub
      study site which required a rigorous evaluation every six weeks for the first two
      years. Each visit included extensive blood studies, neurological and physical
      exams by separate physicians. Magnetic Resonance Imaging (MRI) and evaluation by
      a research nurse. In addition, participants learned to administer the study
      medication subcutaneously every second day and keep extensive diaries of possible
      side effects, concomitant medications, neurological signs and symptoms, and
      incidental environmental events. The attrition rate was low (8%) despite the
      gruelling requirements of the study. As patients completed their course of
      therapy (and before unblinding took place) they were asked to complete a simple
      questionnaire about various aspects of the study. Questions explored their
      reasons for participation, helpfulness of preparatory information, positive and
      negative aspects during the trial, and their "guess" at what they were receiving.
      This paper will summarize the results of the questionnaires and offer suggestions
      for consideration when organizing long-term outpatient clinical trials.

PMID- 7727298
TI  - Gabapentin (NEURONTIN)--a novel anticonvulsant.
AB  - Gabapentin represents a significant advance in the management of epilepsy. To
      date, it appears to be most useful as an add-on therapy for patients with partial
      seizures uncontrolled by standard anticonvulsants. Side effects are mild and
      often subside with continued therapy. Unlike traditional anticonvulsants,
      gabapentin lacks significant drug interactions.

PMID- 7727300
TI  - An analysis of radiotherapy in the management of 104 patients with parotid
      carcinoma.
AB  - A retrospective analysis was made of 104 patients with parotid carcinoma treated
      with radical radiotherapy between 1977 and 1986. Eighty-seven patients received
      postoperative radiotherapy and 17 had radiotherapy alone. The 5- and 10-year
      survival figures, corrected for intercurrent deaths, were 60% and 49%
      respectively, with primary control rates of 68% and 58%. Local control was
      significantly better for patients initially presenting with T1/T2 disease, but
      local relapse still occurred in 23% of these patients. Of 13 patients with acinic
      cell tumours, four developed local recurrence and a further two had metastatic
      disease. These patterns of relapse suggest that patients with parotid carcinoma
      should receive postoperative radiotherapy irrespective of disease stage or
      histological type.

PMID- 7727299
TI  - Epirubicin chemotherapy and advanced breast cancer after adjuvant CMF
      chemotherapy.
AB  - There have been conflicting reports on the effect of prior adjuvant chemotherapy
      on the response of advanced breast cancer to primary chemotherapy. We report a
      retrospective review of the outcome of chemotherapy with epirubicin 100 mg/m2 for
      advanced breast cancer in 39 patients who had previously received adjuvant
      cyclophosphamide, methotrexate and 5-fluorouracil (CMF). The response rate
      (complete responses plus partial responses) was 38.5%, with a median duration of
      response of 33 weeks. There was no significant difference in the response rate or
      duration of survival when these patients were compared with matched controls who
      had not received adjuvant chemotherapy. However, the limitations of this study
      were such that an adverse effect of adjuvant CMF on the response to epirubicin
      cannot be excluded.

PMID- 7727301
TI  - Non-small cell lung cancer: are we out of step?

PMID- 7727302
TI  - The 1994 Crookshank Lecture of the Royal College of Radiologists, given by
      William Reid. Medical attitudes and patients' perceptions.

PMID- 7727303
TI  - Rare tumours of the cerebellopontine angle.
AB  - The vast majority of cerebellopontine angle (CPA) tumours are acoustic neuromas.
      However, in our series of 305 CPA tumours, one in five was another pathological
      lesion. Of the non-acoustic tumours, the majority were meningiomas, primary
      cholesteatomas and glomus jugulare tumours. A variety of rarely seen but
      fascinating pathologies were also treated. A study of these non-acoustic tumours
      has been carried out, looking at their relative incidence, histology and clinical
      features, as well as the radiological features that make them unusual and help to
      distinguish them from acoustic neuromas (vestibular schwannomas). The
      otoneurosurgical procedures required to excise these intriguing lesions are also
      discussed.

PMID- 7727304
TI  - Gene therapy: from fiction to factual tool?

PMID- 7727305
TI  - Knowing just how effective is treatment: implications for care of cancer
      patients.

PMID- 7727306
TI  - Seminoma and squamous cell carcinomas in association with lymphopenia.
AB  - A patient with a seminoma, squamous cell carcinomas of the skin and anus, Bowen's
      disease and lymphopenia is reported. The underlying aetiology is thought to be
      impaired cell mediated immunity and susceptibility to viral infections.

PMID- 7727307
TI  - External beam radiation therapy as an agent in the aetiology of carcinoma of the
      bile duct: a report on two patients.
AB  - Two cases of biliary duct carcinoma occurring in patients who had received
      prophylactic abdominal irradiation 17 years previously are described. Although
      external beam radiation has been implicated in the aetiology of many
      malignancies, there is only one previous report of it being associated with
      carcinoma of the bile duct. All patients receiving external beam irradiation for
      curable malignancies require long term follow-up so that treatment induced
      malignancies may be detected.

PMID- 7727308
TI  - Squamous cell carcinoma of the anus in patients with AIDS.
AB  - Squamous cell carcinoma of the anus accounts for 2%-3% of all malignancies of the
      lower gastrointestinal tract. There is an increased incidence in homosexual males
      who practise receptive and anal intercourse [1]. We report on three cases of
      squamous cell carcinoma of the anus in patients with the acquired immune
      deficiency syndrome (AIDS), all of whom were treated with conventional
      radiotherapy. Increased normal tissue damage with delayed healing was a severe
      problem in each patient. This led to prolonged delays in delivering an adequate
      dose of radiotherapy to the site of disease. Reasons for this are explored and
      suggestions made for the treatment of such patients in the future.

PMID- 7727309
TI  - Renin-producing leiomyosarcoma originating in the uterus.
AB  - We present a case of uterine leiomyosarcoma in a 60-year-old woman, who had
      severe hypertension with hypokalaemia and metabolic alkalosis. Investigation
      revealed an elevated serum renin level; the tumour stained for renin on
      immunocytochemistry. The serum renin level fell on successful treatment of the
      primary. We suggest that this is the first reported case of uterine
      leiomyosarcoma shown to be producing renin.

PMID- 7727311
TI  - Thrombocytopenia with absent radii (TAR) syndrome: a new increased cellular
      radiosensitivity syndrome.
AB  - A 70-year-old woman with congenital absence of both radii but preservation of the
      thumb developed a marked pancytopenia after two i.v. injections of 1 g of 5
      fluorouracil (5-FU) 1 week apart. She developed bloody diarrhoea after nine
      fractions of 2 Gy to parallel opposed 16 x 15 cm abdominal fields. This unusual
      response prompted an investigation of the radiosensitivity of the patient's cells
      by the sensitive G2 assay of transformed lymphocytes. The radiosensitivity of the
      patient's lymphoblastoid line appeared to be intermediate between that of normal
      individuals and an ataxia telangiectasia line. The clinical response and in vitro
      radiosensitivity testing suggest that the thrombocytopenia with absent radii
      (TAR) syndrome appears to be one of the inherited impaired DNA repair syndromes
      and is a very newly described radiation sensitivity syndrome. The development of
      three separate primary cancers in this patient (small bowel, ovary and bladder)
      suggests there is an increased risk of neoplasia in this condition.

PMID- 7727310
TI  - Primary non-Hodgkin's lymphoma of the thyroid with bone marrow infiltration at
      presentation.
AB  - Primary non-Hodgkin's lymphoma of the thyroid is predominantly a disorder of
      elderly females. Most patients present with limited disease and receive local
      irradiation. Presentation with advanced disease is uncommon and, consequently,
      bone marrow examination is not always done. We report a patient with primary
      thyroid lymphoma who had bone marrow infiltration at presentation and discuss the
      importance of this investigation in management.

PMID- 7727312
TI  - Radiotherapy induced soft tissue sarcoma: an unusual case of a
      dermatofibrosarcoma protuberans.
AB  - We report a patient with unusual high grade dermatofibrosarcoma protuberans,
      confirmed by immunohistochemistry, which developed at radiotherapy field margins
      5.7 years after radiotherapy for a squamous cell glottic cancer. The sarcoma
      relapsed locally after inadequate excision and developed lung metastases, as
      confirmed by fine needle aspiration. Radiotherapy induced soft tissue sarcomas
      may differ histologically from their spontaneous counterparts. Even a low
      radiation dose at the field margins can induce a soft tissue sarcoma.

PMID- 7727313
TI  - Cutaneous B-cell lymphoma with subsequent laryngeal involvement.
AB  - Cutaneous lymphoma is uncommon and lymphomatous infiltration of the larynx,
      occurring either as primary disease or as a feature of multifocal disease, is
      rare. We report a case of cutaneous, high grade non-Hodgkin's lymphoma with
      isolated relapse in the larynx. The laryngeal deposit was identical to the
      original cutaneous lymphoma, demonstrated histologically and using the polymerase
      chain reaction. Complete remission of the primary lesion was attained with local
      radiotherapy, and a second complete remission with chemotherapy. To date, no case
      of primary cutaneous lymphoma with subsequent involvement of the larynx has been
      reported, but the association is worth documenting, since symptoms referable to
      the larynx are easily overlooked. They may indicate incipient embarrassment of
      the airway, thus requiring urgent investigation and treatment, which is generally
      highly effective.

PMID- 7727314
TI  - Peripheral blood film deposits in a patient with lymphoproliferative disorder.

PMID- 7727315
TI  - Adjuvant therapy with 5-fluorouracil for breast cancer of likely poor prognosis:
      15-year results of a randomized trial.
AB  - In a trial conducted in southeast Scotland between April 1974 and December 1979,
      332 women with invasive breast cancer of Stage I and II with histological
      evidence of node involvement, or who had operable or inoperable Stage III
      disease, were randomized, after primary local therapy (mastectomy, node biopsy
      and radiotherapy for all except the inoperable disease patients who underwent
      radiotherapy alone) to receive 12 4-weekly intravenous injections of 5
      fluorouracil (5-FU), 700 mg/m2 or no systemic therapy. After a median follow-up
      of 15 years from randomization, no difference is shown between the two groups in
      terms of distant relapse (hazard ratio (HR) = 1.02; 95% CI 0.78-1.32), event free
      survival (HR = 1.23; 95% CI 0.97-1.56), or total survival (HR = 1.19; 95% CI 0.93
      1.52). Locoregional relapse is significantly reduced by 5-FU administration (HR =
      1.88; 95% CI 1.20-2.96). The results are similar for the trial as a whole or when
      mastectomy patients are considered alone. Toxicity was minimal with marrow
      suppression in only 19 of 147 patients receiving more than one injection; only
      five patients discontinued therapy due to nausea and vomiting. However,
      retrosternal pain occurred in 16 patients, nine of whom had their treatment
      curtailed as a result. Seventy-seven per cent of patients have died, the majority
      from breast cancer. Only 1.2% of deaths are considered attributable to cardiac
      causes of 5-FU is not associated with excess cardiac deaths in these
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727316
TI  - A high-resolution line sensor-based photostereometric system for measuring jaw
      movements in 6 degrees of freedom.
AB  - Photostereometry has widely been applied to the measurement of mandibular
      movements in 6 degrees of freedom. In order to improve the accuracy of this
      measurement, we developed a system utilizing small LEDs mounted on the jaws in
      redundant numbers and a 5000 pixel linear charge-coupled device (CCD) as a photo
      sensor. A total of eight LEDs are mounted on the jaws, in two sets of four, by
      means of connecting facebows, each weighing approximately 55 g. The position of
      the LEDs are detected in three-dimensions by two sets of three CCD cameras,
      located bilaterally. The position and orientation of the mandible are estimated
      from the positions of all LEDs measured in the sense of least-squares, thereby
      effectively reducing the measurement errors. The static overall accuracy at all
      tooth and condylar points was considered to lie within 0.19 and 0.34 mm,
      respectively, from various accuracy verification tests.

PMID- 7727317
TI  - Characterization of the non-linear loading curve of rat skin.
AB  - A phenomenological model was developed to characterize the non-linear portion of
      stress-strain curves for skin tissue removed from laboratory rats and tangent
      modulus calculations were used to characterize the linear portion of the curves.
      Modified coefficient of determination calculations obtained from non-linear
      regression analysis showed that the model was able to fit the actual data above
      the 90% level. The model coefficients and tangent modulus values were used to
      statistical comparisons. Combination treatments of radiation, hyperthermia and
      surgical incision were used to analyze changes in the loading response of rat
      skin. Least significant difference statistical analysis (P < 0.10) of the model
      coefficients showed that radiation treatment affected skin stiffness only in
      tissue when surgical wounding was applied and that radiation-hyperthermia
      treatment affected skin stiffness only in tissue when surgical wounding was not
      applied. Hyperthermia applied with no radiation treatment did not affect skin
      stiffness. Surgical wounding resulted in decreasing skin stiffness.

PMID- 7727318
TI  - Determination of the kinematic axis point of the temporomandibular joint
      regardless of cyclic mandibular movement data.
AB  - The term 'kinematic axis' refers to a theoretical intercondylar axis of the
      mandible, any point on it nearly reciprocating on a single surface during all
      sagittal movements. Thus the axis can simplify kinematic features of the
      temporomandibular joint. In order to locate the axis point on a desired sagittal
      plane kinematically, a cyclic mandibular movement along the sagittal border has
      been employed, due primarily to its locational efficiency. For purposes of
      extracting entire features of condylar movements, however, not only the border
      movement, but as many other types of movements as possible should be employed.
      Location methodology applicable to such a wide variety of movement data has yet
      to be established. To surmount this restriction, this paper presents a technique
      applicable to any sagittal movement data. The axis point can be obtained as a
      condylar point, the motion range of which is the narrowest. This range has been
      provided as the region surrounded by a closed trajectory, whereas it is here
      defined by the region lying between the superior and inferior trajectories,
      thereby achieving a discarding of kinetic cyclicity. A condylar point minimizing
      the area of this region was verified to be a valid estimate of the kinematic axis
      point, through experiments employing actual mandibular movement data.

PMID- 7727319
TI  - Optimum apportionment of presentation time in visual display.
AB  - With regard to the better display of visual stimuli, one of the key parameters to
      match with human short-term memory is the presentation time of the information.
      We have studied the optimum-apportionment modes of the presentation time of seven
      Roman alphabet letters sequentially presented to five young males by means of our
      time-continuous model of short-term memory. These modes are thought to allow for
      the easiest retention by the short-term memory. The average optimum-apportionment
      mode, as an average of individual scores of the optimum-apportionment mode, was
      also obtained. With free-recall experiments using the Roman characters, four
      constants for the model were determined for the subjects. Then, the theoretical
      optimum-apportionment modes were calculated using a computer simulation for each
      subject. With slight modifications of these results, eight types of apportionment
      modes were obtained. The most efficient mode for the recall of the Roman
      characters in the free-recall experiment was determined as the optimum
      apportionment mode of the individual.

PMID- 7727320
TI  - Method for quantifying the contribution of overlying tissue to rat liver 31P-NMR
      spectra using the surface-coil technique.
AB  - A method for quantitatively analyzing the overlying tissue contribution to the in
      vivo 31P-NMR spectra from rat liver observed by the surface-coil technique is
      presented. The peak area of beta-ATP obtained either through the abdominal wall
      or directly from the liver was compared before and after occlusion of the portal
      vein or infusion of fructose. The phosphocreatine (PCr) signal is a
      characteristic signature of the 31P spectrum of muscle, and did not differ before
      and after portal vein occlusion or fructose infusion. After 30 min of occlusion,
      the beta-ATP obtained through the abdominal wall decreased to 25% of its initial
      value and that taken directly from the liver almost disappeared. Accordingly, the
      overlying tissue contribution to the in vivo liver spectra could be
      quantitatively assessed from the post-occlusion reduction of the beta-ATP peak in
      the spectra. The recovery of the beta-ATP concentration 10 min after fructose
      infusion should also reflect the augmentation of ATP synthesis in the liver. The
      difference of 25% in beta-ATP concentration between the spectra obtained through
      the abdominal wall and those directly from the liver following fructose infusion
      showed the overlying tissue contribution. We demonstrated that this contribution
      was 25% for the liver spectra obtained through the abdominal wall and 75% of the
      components in the spectra originated from the rat liver in our surface-coil
      measurements.

PMID- 7727321
TI  - Treatment of sympathetically maintained pain. Quod erat demonstrandum.

PMID- 7727322
TI  - Anatomy of the lumbar sympathetic chain.
AB  - BACKGROUND AND OBJECTIVES: To acquire an accurate knowledge of the relationship
      of the sympathetic chain to the vertebral column. METHODS: In dissections on 65
      cadavers the authors located the sympathetic chain and its ganglia in three
      dimensions with respect to the vertebral column: cephalad-caudad in the sagittal
      plane; ventrally and laterally in the horizontal (axial) plane. The relationship
      of the sympathetic chain to the psoas muscle and that of the psoas muscle to the
      vertebral column was also established. Transparent markers were placed at each
      disk space and colored markers at each grossly recognizable ganglion. Photographs
      and measurements were then made. RESULTS: In the sagittal plane, the lumbar
      ganglia were most often present opposite the middle of the body of the third
      vertebra and at the disks above and below. In the horizontal plane, the ganglia
      lay from 0 to 0.5 cm posterior to the anterior border of the third lumbar
      vertebra and 1.8 to 3.0 cm laterally from the center of the third lumbar
      vertebra. The sympathetic chain always lay anterior to the psoas muscle.
      CONCLUSIONS: Although the location of the ganglia is quite variable, the best
      approach for sympathetic block is to advance the needle paravertebrally through
      the fascia of the psoas muscle slightly cephalad to the midpoint of the body of
      L3.

PMID- 7727323
TI  - Bupivacaine toxicity in lightly anesthetized pigs with respiratory imbalances
      plus or minus halothane.
AB  - BACKGROUND AND OBJECTIVES: Changes in acid base balance within the body, oxygen
      delivery to tissue, and carbon dioxide elimination, as well as general
      anesthetics, influence the toxicity of local anesthetics. The objective of this
      study was to test the hypothesis that light halothane anesthesia, hypercapnia,
      and hypoxia act together to alter the central nervous system and cardiovascular
      toxicity of bupivacaine. METHODS: Three groups of 2-week-old pigs were lightly
      anesthetized with N2O in O2 and paralyzed with pancuronium. One group (n = 6) was
      made hypercapnic (group A; PaCO2 > or = 60 mg Hg), another group (n = 6) was made
      hypercapnic and hypoxic (group B; F1O2 = 0.1, PaCO2 = 66.8 +/- 9.91 mm Hg, PaO2 =
      29.2 +/- 3.53 mm Hg), and another group (group C; n = 5) was made hypercapnic and
      hypoxic and given 0.5% halothane (PaCO2 = 68.54 +/- 4.18, PaO2 = 31.06 +/- 1.96).
      Bupivacaine was infused intravenously at 1 mg.kg-1.min-1 until the animals
      developed cardiac asystole. RESULTS: Arrhythmias, seizures, isoelectric
      electroencephalogram (isoEEG), and asystole were readily identified in groups A
      and B. None of the animals given halothane had seizures, but they did exhibit the
      other three toxic endpoints. The doses of bupivacaine producing asystole were
      significantly less in group C than in group A (7.9 +/- 1.8 versus 17.7 +/- 2.2
      mg.kg-1). The doses of bupivacaine that produced isoEEG were significantly lower
      in groups B and C than in group A (8.9 +/- 6.2, 5.0 +/- 1.1, 14.6 +/- 3.2 mg/kg,
      respectively). Doses of bupivacaine producing all toxic endpoints except seizures
      were lower in group B animals than in group A, but only the isoEEG doses were
      statistically different (arrhythmias 2.3 +/- 1.1 versus 3.7 +/- 1.1; isoEEG 8.9
      +/- 6.2 versus 14.6 +/- 3.2; asystole 12.1 +/- 7.5 versus 17.7 +/- 2.2 mg.kg-1).
      No differences in seizure pattern or type of arrhythmia were detected. Mean
      arterial pressure decreased during bupivacaine infusion, the rate of decrease was
      fastest (P < .05) in the animals receiving halothane and slowest in the
      hypercapnic animals. Mean arterial pressure in group A increased significantly
      compared to control (to 135.5 +/- 14.4% of control; P < .01) before decreasing.
      Heart rate decreased and the differences over time among groups differed
      significantly. CONCLUSIONS: Bupivacaine is significantly more lethal, as judged
      by the doses producing asystole, in young pigs that are hypercapnic, hypoxic, and
      receiving halothane than in young pigs that are hypercapnic.

PMID- 7727324
TI  - Continuous high thoracic epidural administration of morphine with bupivacaine
      after thoracotomy.
AB  - BACKGROUND AND OBJECTIVES: The purpose of the study is to determine the ideal
      concentration of morphine when given with bupivacaine as a continuous high
      thoracic epidural infusion for postthoracotomy pain. METHODS: In a prospective
      study, 60 patients scheduled for thoracic surgery received a high thoracic
      epidural catheter. Postoperative analgesia was provided by a continuous epidural
      infusion for 3 days. The patients were randomly divided into two groups: group 1
      (loading dose 1 mg morphine epidurally and continuous infusion of bupivacaine
      0.75% + 0.2 mg/mL morphine at an infusion rate of 0.8 mL/hr); group 2 (loading
      dose 0.5 mg morphine epidurally and continuous infusion of bupivacaine 0.75% +
      0.1 mg/mL morphine at an infusion rate of 0.8 mL/hr). RESULTS: The visual analog
      scales were not different at rest but with exercise in group 1 there was better
      pain relief than in group 2. The number of patients requiring supplementation of
      analgesia in group 2 (n = 42) was six times that of group 1 (n = 7). PaCO2
      increased in both groups during the first postoperative day. There was no
      difference in the incidence of side effects between the two groups. CONCLUSIONS:
      Continuous high thoracic epidural administration 0.2 mg/mL morphine in
      bupivacaine 0.75% at an infusion rate of 0.8 mL/hr with a loading dose of 1 mg
      morphine is an effective dose for postthoracotomy pain relief in rest, and more
      important, during exercise.

PMID- 7727325
TI  - Radiofrequency lumbar sympatholysis. The evolution of a technique for managing
      sympathetically maintained pain.
AB  - BACKGROUND AND OBJECTIVES: To develop lumbar radiofrequency sympatholysis for the
      relief of pain in patients with neuropathic pain who had previously responded to
      sympathectomy or sympathetic blocks. METHODS: The technique described by Sluijter
      was modified to attempt to obtain long lasting pain relief in each patient. No
      one technique was universally applicable. The variations in technique are
      illustrated by the case reports. The basic technique that evolved is as follows:
      a 20-gauge 15-cm insulated needle with a 5-mm active tip was inserted in the
      direction of an x-ray beam (C arm). The initial target was slightly cephalad to
      the middle of the L3 vertebra. Contrast medium was injected to confirm the
      location of the needle. The temperature of the tip of the needle was controlled
      at 80 degrees C for 90 seconds. RESULTS: Thirty-eight procedures were performed
      on 20 patients. Reproduction of the pain for which the sympatholysis was
      undertaken, induced dysesthesia, spread of dye, rapidity of temperature rise in
      the legs, and increase in pulse volume of the toes were useful guides to proper
      placement of the needle. Five patients continue to be pain free 5 months to 3
      years after the last radiofrequency sympatholysis. Fifteen had temporary relief
      or no relief at all. The procedure was temporarily complicated by an excessively
      hot, swollen foot, and postsympathectomy neuralgia in a few cases. CONCLUSIONS: A
      single technique of radiofrequency sympatholysis does not appear to be applicable
      to all patients with reflex sympathetic dystrophy or sympathetically maintained
      pain. Despite early successful sympathetic block with radiofrequency, as
      confirmed by a warm foot, long lasting pain relief was difficult to obtain. The
      author concludes that individualized patient management is necessary when
      considering radiofrequency sympatholysis in the treatment of patients with
      sympathetically maintained pain.

PMID- 7727326
TI  - Hemodynamic effects of 0.375% versus 0.25% bupivacaine during cervical epidural
      anesthesia for hand surgery.
AB  - BACKGROUND AND OBJECTIVES: Cervical epidural anesthesia with 0.375% or 0.25%
      bupivacaine plus fentanyl is a reliable technique for surgical restoration of
      digital motion-after tourniquet release and rehabilitation. The study was
      designed to assess the hemodynamic effects of this technique in 11 ASA 1
      patients. METHODS: The epidural catheter was introduced at the C7-T1 interspace
      on the day of operation. The volume of 0.375% bupivacaine necessary to block the
      brachial dermatomes was determined. The day after (day 1), every patient received
      epidurally the determined volume of 0.375% bupivacaine plus 1 microgram/kg
      fentanyl (group A). On day 2 the same volume of 0.25% bupivacaine plus 1
      microgram/kg fentanyl (group B) was injected. For each patient one or several
      pairs of injection (A + B) were performed in relation with duration of
      rehabilitation. Cardiac index, stroke volume index, end diastolic index, ejection
      fraction, and systemic vascular resistance were studied by thoracic electrical
      bioimpedance. These parameters, mean arterial pressure and heart rate were
      recorded before and after injection. Sensory level was assessed by loss of cold
      sensation. RESULTS: Nineteen paired injections were performed. Mean volume of
      bupivacaine was 7.1 +/- 2 mL. The caudad sensory level was lower in group A: T7
      (T3-L1) versus T6 (T2-T11) in group B. Hemodynamic variables were not different
      between the 2 groups. Mean arterial pressure cardiac index, heart rate, stroke
      volume index, and ejection fracture decreased slightly as end diastolic index
      remained unchanged and systemic vascular resistance increased slightly. No
      correlation was found between hemodynamic changes and spread of analgesia.
      CONCLUSIONS: Hemodynamic effects, in ASA 1 patients, are moderate and not
      dependent on the studied concentration of bupivacaine, indicating that a similar
      degree of sympathetic block is achieved with 0.375% and 0.25% bupivacaine.

PMID- 7727327
TI  - Prolonged PR interval is a risk factor for bradycardia during spinal anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Bradycardia occurs during 9%-13% of spinal anesthetics
      and may lead to cardiac arrest. Several risk factors for the development of
      bradycardia have been identified, but the risk conferred by presence of
      abnormalities detected on preoperative electrocardiogram (ECG) has not been
      examined. The authors undertook the study to correlate abnormal ECG findings with
      the incidence of bradycardia. METHODS: The data-base was previously collected
      from 952 patients undergoing spinal anesthesia. Patient records were reviewed and
      537 had ECGs performed within 6 months of surgery. Intraoperative bradycardia was
      defined as a heart rate < 50 bpm (plus > 10% decrease from baseline).
      Abnormalities recorded from the ECG were prolonged PR interval (PR > 0.2 sec),
      atrial-ventricular conduction abnormalities, evidence of chamber hypertrophy,
      ischemia, and infarction. The findings were compared with incidence of
      bradycardia using contingency tables. Significant correlations were then
      evaluated with logistic regression. Significance was defined as P < .05. RESULTS:
      The incidence of bradycardia in this population was 12%. Patients with a
      prolonged PR interval had an increased incidence of bradycardia (25%, P = .01).
      Other ECG abnormalities did not correlate with increased incidence of
      bradycardia. Duration of PR interval did correlate significantly (P = .001) but
      poorly (r2 = 0.014) with baseline heart rate. However, logistic regression
      demonstrated that prolonged PR interval was a significant and independent
      predictor for bradycardia (odds ratio = 3.2, P = .01). CONCLUSIONS: Risk factors
      previously identified for the development of bradycardia during spinal anesthesia
      include: baseline heart rate < 60 bpm, ASA physical status 1 versus 3 or 4, use
      of beta-blocking drugs, sensory block height > or = T5, and age < 50. The results
      demonstrate that prolonged PR interval on the preoperative ECG is another
      significant and independent predictor for bradycardia.

PMID- 7727328
TI  - Effects of drug dose, volume, and concentration on spinal anesthesia with
      isobaric tetracaine.
AB  - BACKGROUND AND OBJECTIVES: Factors governing the spread of local anesthetic in
      the subarachnoid space have been controversial because of failure to consider the
      drug related and physical factors. Most studies of isobaric spinal anesthesia in
      the literature were made using plain bupivacaine which is slightly hypobaric. In
      this study the effects of drug dose, volume, and concentration were investigated
      employing isobaric tetracaine (IT). METHODS: One hundred twenty patients were
      randomly allocated to four groups to receive IT diluted to appropriate
      concentrations with cerebrospinal fluid. Drugs were administered in lateral
      position at L3-4 level, with the patient remaining horizontal (supine) during the
      study. Neural block was assessed by pinprick and the Bromage scale. Except for
      the factor under investigation, identical techniques were used. RESULTS: Data
      indicated that volume was the immediate major factor affecting the extent of
      spread reflected by the significant difference in peak levels between group 1 and
      group 2 patients. When volume remained constant, increasing dose (mass)
      concomitantly increased concentration resulting in a faster onset, longer block,
      and a higher peak level. However, this effect was not prominent and often limited
      as increasing the dose from 15 mg to 20 mg had no significant effect on the peak
      levels in group 3 and group 4 patients. CONCLUSIONS: In IT spinal anesthesia, the
      role of baricity/posture interaction no longer exists, the volume appears the
      most significant factor by simple bulk displacement or area of contact. Next in
      significance is the dosage. Increased dose in the same volume implies an increase
      in concentration that results in faster onset and longer duration and, to a less
      extent, the peak level.

PMID- 7727329
TI  - A reevaluation of the association between instrument delivery and epidural
      analgesia.
AB  - BACKGROUND AND OBJECTIVES: Over 100 papers in the medical literature suggest pro
      or con that epidural analgesia is associated with an increase in the incidence of
      instrument delivery. This two-component study was performed to evaluate the
      influence of epidural labor analgesia on the incidence of instrument delivery.
      METHODS: Component 1 was a retrospective analysis of the medical records of
      14,804 mothers having a vaginal delivery before and after implementation of an
      active epidural service. Component 2 was a case control study designed to
      determine factors, in addition to epidural analgesia, associated with an increase
      in instrument delivery. In component 2 11 factors describing maternal, fetal,
      anesthetic, and obstetric factors were analyzed for each of 609 consecutive
      patients having an instrument delivery and 246 controls having a spontaneous
      vaginal delivery. RESULTS: In component 1, despite a tenfold increase in the use
      of epidural analgesia, there was a similar association between epidural use and
      instrument delivery in both time periods. Additionally, the epidural-forceps
      association was twice as strong for parous patients as for nulliparous patients
      (odds-ratios 9.74 and 4.52, respectively). In component 2, five factors were
      significantly (P > .0001) associated with instrument delivery conclusions.
      CONCLUSIONS: While epidural analgesia was one factor, the others were gestational
      age > 41 weeks, a second stage of labor > 2 hours, an occiput posterior or
      transverse fetal position, and previous cesarean section. These four factors are
      individually and independently associated with an increase in the incidence of
      instrument delivery independent of epidural use.

PMID- 7727330
TI  - Addition of clonidine to epidural morphine enhances postoperative analgesia after
      cesarean delivery.
AB  - BACKGROUND AND OBJECTIVES: The randomized, double-blind, dose-response study was
      designed to evaluate the effects of the addition of clonidine to epidural
      morphine on postoperative analgesia and side effects in patients undergoing
      cesarean delivery. METHODS: Sixty patients, undergoing cesarean delivery under
      epidural anesthesia, were randomly divided in three equal groups to receive, at
      the end of surgery, an epidural analgesic mixture consisting of 10 mL solution
      containing 2 mg of morphine diluted with 0.125% bupivacaine plus 1:800,000
      epinephrine and 0, 75, or 150 micrograms of clonidine. Duration of analgesia was
      assessed as the pain-free interval between the end of surgery and patient's first
      analgesic request. The analgesic mixture was repeated, on patient's request, to
      36 hours after the operation. Arterial blood pressure, heart rate, respiratory
      rate, and side effects were noted. The total amount of morphine and clonidine
      delivered was also noted. RESULTS: The addition of clonidine (0, 75, or 150
      micrograms) to morphine significantly increased the duration of postoperative
      analgesia (P < .0001) (6.27 versus 13.25 and versus 21.55 hours) and reduced the
      mean total dose of morphine (9.40 mg versus 5.0 mg versus 3.60 mg) (P < .0001).
      No significant differences in side effects were noted. CONCLUSIONS: A low dose of
      clonidine such as 75 micrograms doubled the duration of analgesia produced by 2
      mg of morphine and a dose of 150 micrograms further increased the duration of
      postoperative complete analgesia without increasing the incidence of side
      effects. The morphine requirements during the postoperative period (36 hours) was
      greatly reduced by the addition of clonidine to the analgesic epidural mixture.

PMID- 7727331
TI  - A retrospective comparison of interscalene block and general anesthesia for
      ambulatory surgery shoulder arthroscopy.
AB  - BACKGROUND AND OBJECTIVES: An increasing percentage of all surgery is performed
      in an ambulatory surgery setting. Concurrently, arthroscopy of the shoulder joint
      has allowed definitive repair of shoulder pathology to occur in this environment.
      This study was designed to ascertain whether interscalene block is reliable and
      efficient for use in same-day surgery compared with general anesthesia for
      shoulder arthroscopy. METHODS: The authors retrospectively reviewed patients
      treated at the University of Connecticut over a 42-month period in the same-day
      surgery unit. Of 263 patients, 160 had a general anesthetic and 103 had an
      interscalene block. All times recorded for the study were contemporaneously
      logged into the operating room computer data base from which they were extracted.
      Data on complications were retrieved from individual patient charts and hospital
      quality assurance files. RESULTS: Compared to general anesthesia, regional
      anesthesia required significantly less total nonsurgical intraoperative time use
      (53 +/- 12 vs. 62 +/- 13 minutes, P = .0001) and also decreased postanesthesia
      care unit stay (72 +/- 24 vs. 102 +/- 40, P = .0001). Interscalene block
      anesthesia resulted in significantly fewer unplanned admissions for therapy of
      severe pain, sedation, or nausea/vomiting than general anesthesia (0 vs. 13, P =
      .004) and an acceptable failure rate (8.7%). CONCLUSIONS: Interscalene block
      should be considered as a viable alternative to general anesthesia for shoulder
      arthroscopy in ambulatory surgery patients.

PMID- 7727332
TI  - Severe lumbar back pain following epidural injection of local anesthetic for
      epidural anesthesia. Case report and literature review.
AB  - BACKGROUND AND OBJECTIVES: An epidural anesthetic was planned for a 75-year-old
      man scheduled for elective femoral-popliteal bypass grafting. METHODS: Severe and
      persistent back pain and posterior thigh muscle spasm abruptly began 10 minutes
      after epidural injection of mepivacaine. RESULTS: Signs of impending or evolving
      neurologic injury completely resolved shortly thereafter. CONCLUSIONS: The worst
      case scenarios, epidural hematoma and unintentional epidural injection of an
      irritant, are discussed along with other differential diagnoses. The literature
      is reviewed to gain insight into this unusual clinical presentation.

PMID- 7727333
TI  - Postlaminectomy pseudomeningocele. An unsuspected cause of low back pain.
AB  - BACKGROUND AND OBJECTIVES: Patients with postlaminectomy pseudomeningoceles may
      present to pain management centers without having been diagnosed previously.
      Practitioners treating chronic low back pain need to be aware of this potential
      hazard. METHODS: Retrospective analyses of six such cases was made including:
      clinical signs and symptoms, radiological findings, and possible therapeutic
      modalities. RESULTS: In every case, there was a palpable fluctuating mass under
      the surgical scar, sensory loss in both lower extremities, and limited leg
      raising; moreover, heel tapping produced pain. Also, every patient had a history
      of long standing cigarette smoking and multiple spinal surgeries. Radiologically
      dural saccular or tubular structures were noted at myelograms, magnetic resonance
      imaging, or computed axial tomography scan, usually at the site of the surgery.
      In one patient with metallic devices, diagnosis was made by ultrasound.
      CONCLUSIONS: The need for a complete examination by the pain specialist is
      emphasized since instrumentation in attempts to perform invasive procedures,
      i.e., inserting needles in the patients, may result in unintentional puncture of
      the pseudomeningocele and cerebrospinal fluid leaks. The clinical features
      accompanying the surgical complications ought to be recognized as a warning
      signal.

PMID- 7727334
TI  - New oxygen mask for clinical practice.

PMID- 7727335
TI  - Comment on sciatic nerve block study by Bailey et al.

PMID- 7727336
TI  - Digital block of the flexor tendon sheath can restore pulse oximeter signal
      detection.

PMID- 7727337
TI  - Response to Dr. Redick's observations.

PMID- 7727338
TI  - Comments to Urban and Urquhart study.

PMID- 7727339
TI  - Special issue: The 1st International Conference on Polysaccharide Engineering.
      Trondheim, Norway, 6-8 June 1994.

PMID- 7727340
TI  - Molecular mechanisms and genetics of hyaluronan biosynthesis.
AB  - Hyaluronan is an extremely important polysaccharide from both the biological and
      commercial points of view. This review summarizes the present state of the art
      concerning the polymer and our understanding of the molecular mechanisms of its
      synthesis with emphasis on the implications of this understanding for
      polysaccharide engineering of hyaluronan.

PMID- 7727341
TI  - Genetic analysis of the acetan biosynthetic pathway in Acetobacter xylinum.
AB  - We have identified, cloned and sequenced an 8422 base pair fragment of
      Acetobacter xylinum genomic DNA containing part of the acetan biosynthetic gene
      cluster. Computer analysis of the nucleotide sequence data generated revealed the
      presence of six open reading frames. Comparison of the translated sequences of
      putative genes to the amino acid sequences of genes from other organisms was used
      to assign functions to the aceA, aceC and manB genes. These genes were predicted
      to encode a UDP-glycosyl transferase, a GDP-mannosyl transferase and a
      phosphomannose isomerase/GDP-mannose pyrophosphorylase, respectively.

PMID- 7727342
TI  - Biosynthesis of a novel polysaccharide by Acetobacter xylinum.
AB  - An Acetobacter xylinum adapted to a medium containing N-acetylglucosamine
      (GlcNAc) has been used to prepare a novel polysaccharide containing residual
      GlcNAc in cellulose. The maximum amount of incorporation was found to be 4 mol%
      in cellulose, when a mixed medium containing 1.4% glucose (Glc) and 0.6% GlcNAc
      was used for the culture of A. xylinum. The resulting polysaccharide was lysozyme
      susceptible. The aminosugar residue incorporated into bacterial cellulose was
      found to be only GlcNAc, even if galactosamine (GalN) and glucosamine (GlcN) were
      applied, whereas there was little effect by mannosamine (ManN). As the major
      component of the resulting polysaccharide was Glc residues, even if the only
      carbon source in the culture medium was GlcNAc, it was suggested that there must
      be several enzyme systems to convert GlcNAc into Glc in the bacteria. Several
      ammonium salts were also found to be effective for the incorporation of GlcNAc
      residues when the incubation system was converted to rotatory and aerobic
      incubation from static incubation. The amount of residual GlcNAc was remarkably
      increased by the addition of lysozyme-susceptible phosphoryl-chitin (P-chitin)
      and increased slightly with addition of P-chitin that was less lysozyme
      susceptible. However, little effect was found on addition of highly substituted P
      chitin.

PMID- 7727343
TI  - Physicochemical properties of extracellular (1-->4)-beta-D-glucuronan produced by
      the Rhizobium meliloti M5N1CS strain during fermentation: evidence of degradation
      by an exoenzyme activated by Mg2+.
AB  - The mutant Rhizobium meliloti M5N1CS (NCIMB 40472) produced a partially
      acetylated (1-->4)-beta-D-glucuronan during fermentation. The polysaccharide
      (EPS) extracted from broth during fermentation by microfiltration and
      ultrafiltration (using a 100 kDa cut-off membrane) was characterized by size
      exclusion chromatography. The weight-average molecular weight (Mw) of the EPS
      decreased from 7.5 x 10(5) to 5 x 10(5) between 27 and 75 h of fermentation. When
      MgSO4.7H2O (0.8 gl-1 per day) was present in the medium during the same period,
      the Mw of the EPS decreased to 1.5 x 10(5). Since EPS degradation was detected
      after microfiltration of the fermentation medium supplemented with magnesium, the
      Mw decrease of the EPS extracted during fermentation may be explained by enzymic
      degradation of the polymer activated by Mg2+ ions.

PMID- 7727344
TI  - Extracellular polysaccharide of Erwinia chrysanthemi Ech6.
AB  - Many strains of Erwinia chrysanthemi, which are Gram-negative bacterial
      phytopathogens, produce copious amounts of extracellular polysaccharides. The
      extracellular polysaccharide from E. chrysanthemi pv. zeae strain SR 260, a
      phytopathogen of corn, is a branched-chain glucomannorhamnan of proven structure
      (Gray et al., Carbohydr. Res. 1993, 245, 271-287). The extracellular
      polysaccharide from E. chrysanthemi Ech6 is different, containing no rhamnose or
      mannose. It is composed of L-fucose, D-galactose, D-glucose and D-glucuronic acid
      in the ratio 2:2:1:1. The structure of the polysaccharide is as follows:
      [sequence: see text]

PMID- 7727345
TI  - Conformation of (2-->1)-beta-D-fructan in aqueous solution.
AB  - The conformation and dilute solution properties of (2-->1)-beta-D-fructan in
      aqueous solution were studied by gel permeation chromatography, low-angle laser
      light-scattering photometry, viscometry, small-angle X-ray scattering and
      electron microscopy. Fractions covering a broad range of weight-average molecular
      weights (Mw) from 1.49 x 10(4) to 5.29 x 10(6) were obtained from a native sample
      by ultrasonic degradation and fractional precipitation. For Mw < 4 x 10(4), the
      intrinsic viscosity [eta] varies with Mw0.71, indicating that the fructan chain
      behaves as a random coil expanded by an excluded-volume effect in this molecular
      weight region. For Mw > 10(5), [eta] exhibits an unusually weak dependence on Mw
      and finally becomes almost independent of molecular weight. This behaviour is
      interpreted in terms of a globular conformation of the high-molecular-weight
      fructan molecules. Small-angle X-ray-scattering measurements and electron
      microscopic observations support this interpretation of the values of [eta]
      observed.

PMID- 7727346
TI  - Hydrodynamic characteristics and equilibrium rigidity of pullulan molecules.
AB  - The hydrodynamic characteristics of the polysaccharide pullulan (polymaltotriose)
      in water have been investigated and its molecular characteristics have been
      determined. Experimental values varied over the following ranges: velocity
      sedimentation coefficient (S): 0.9 < S < 11.2, translational diffusion
      coefficient (10(7) cm2 s-1): 1.1 < D < 14.7 and intrinsic velocity (cm3 g-1): 6.7
      < [eta] < 164, which corresponds to a change in molecular weight (x 10(3)) in the
      range 3.9 < MSD < 644. On the basis of analysis of the literature and our
      experimental data, excluded volume effects have been shown to have a prevailing
      influence on the chain length of these polysaccharides. The equilibrium rigidity
      and hydrodynamic chain diameter of pullulan were evaluated on the basis of the
      theory of hydrodynamic properties of a wormlike necklace, taking into account
      excluded volume effects. At low M (< 30 x 10(3)) the translation friction data
      (in contrast to viscometric data) cannot be described in the framework of the
      theory of linear molecules.

PMID- 7727347
TI  - Physicochemical characterization of an acetan variant secreted by Acetobacter
      xylinum strain CR1/4.
AB  - Chemical mutagenesis has been used to produce mutants of Acetobacter xylinum NRRL
      B42 that are cellulose-negative and that produce variants of the acetan structure
      deficient in the side-chain sugar residues. The product of A. xylinum strain
      CR1/4 has been shown to possess a tetrasaccharide repeat unit with the side chain
      terminating in glucuronic acid. X-ray diffraction studies of oriented fibres
      suggest that the polysaccharide CR1/4 forms a fivefold helix with a pitch of 4.8
      nm. Light-scattering studies on CR1/4 solutions suggest a molecular weight of 1.2
      x 10(6) with radii of gyration values of 86 nm (aqueous solution) and 67 nm (0.1
      M NaCl solution). The magnitude of the measured radii of gyration and the shape
      of the Holtzer plots suggest that CR1/4 can be described as a stiff coil.
      Preliminary differential scanning calorimetry data show melting behaviour
      consistent with order-disorder transitions of a charged helical structure.
      Rheological studies have revealed new synergistic interactions of CR1/4 with
      locust bean gum. Comparative studies of acetan and CR1/4 show that decreasing the
      length of the side chain enhances the solution viscosity.

PMID- 7727348
TI  - Enzymatic synthesis of trisaccharides and alkyl beta-D-glucosides by the
      transglycosylation reaction of beta-glucosidase from Fusarium oxysporum.
AB  - Purified beta-glucosidase from Fusarium oxysporum catalyses hydrolysis and
      transglycosylation reactions. By utilizing the transglycosylation reaction,
      trisaccharides and alkyl beta-D-glucosides were synthesized under optimal
      conditions in the presence of various disaccharides and alcohols. The yields of
      trisaccharides and alkyl beta-D-glucosides were 22-37% and 10-33% of the total
      sugar, respectively. The enzyme retained 70-80% of its original activity in the
      presence of 25% (w/v) methanol, ethanol and propanol. Thus, beta-glucosidase from
      F. oxysporum appears to be an ideal enzyme for the synthesis of useful
      trisaccharides and alkyl beta-D-glucosides.

PMID- 7727349
TI  - Isolation of four major subunits from Clostridium thermocellum cellulosome and
      their synergism in the hydrolysis of crystalline cellulose.
AB  - The cellulosome of Clostridium thermocellum, purified by affinity chromatography,
      was dissociated under mild conditions and separated by SDS-PAGE. Two major p
      nitrophenylcellobiosidases (PNPCases I and II) corresponding to the S5 (103 kDa)
      and S8 (78 kDa) subunits and one major carboxymethylcellulase (CMCase) coinciding
      with the S11 (60.5 kDa) subunit were isolated and characterized using
      carboxymethylcellulose (CMC), H3PO4-swollen cellulose and cello-oligosaccharides.
      Both PNPCases showed little effect on the viscosity of CMC and released twice as
      much total sugar as reducing sugar from H3PO4-swollen cellulose. The CMCase
      released ten times more total sugar than reducing sugar from H3PO4-swollen
      cellulose and reduced the viscosity of CMC rapidly. None of these enzymes was
      active on cellotriose. Both PNPCases released cellobiose from cellotetraose, and
      cellobiose and cellotriose from cellopentaose. In contrast, CMCase was active
      only on cellopentaose and released mainly glucose. Use of MeUmb(Glc)n revealed
      that both PNPCases cleaved preferentially either the second or fourth linkage
      from the non-reducing end while the CMCase was specific for the internal
      glycosidic bonds. Thus, the PNPCases and CMCase behaved as typical exo- and
      endoglucanases, respectively. When tested individually, all three enzymes
      degraded Avicel only to a small extent. A 1.5-2.0-fold increase in sugar release
      was observed when CMCase was combined with either PNPCase I, II or both.
      Combining S1 with either PNPCase II or CMCase resulted in fourfold synergism in
      the hydrolysis of Avicel. Synergism was sevenfold when all three enzymes were
      combined with S1.

PMID- 7727350
TI  - Formation, derivatization and applications of bacterial cellulose.
AB  - Acetobacter xylinum produces highly crystalline cellulose extracellularly using
      glucose as a carbon source. The polymer formed is free of other biogenic
      compounds, separable in a simple way and characterized by its high water
      absorption capacity. Stepwise solvent exchange from water to unpolar solvents
      leads to a drastic decrease of the water content of the bacterial cellulose
      without decrease of the highly swollen and activated state. Heterogeneous as well
      as homogeneous derivatizations, e.g. carboxymethylation, silylation and
      acetylation, were performed on the wet or dried biopolymer. Furthermore,
      different methods for formation of hollow fibres during biosynthesis were
      investigated. Such tubes may have applications as biocompatible material in
      medicine.

PMID- 7727351
TI  - Adjuvant-induced persistent photosensitivity models in guinea pigs. I. Induction
      of persistent photosensitivity.
AB  - Induction of persistent photosensitivity in guinea pigs was carried out in an
      attempt to induce a model suitable to clarify the mechanism of human persistent
      light reactors. Guinea pigs were treated with intradermal injection of adjuvant
      which consisted of desiccated Mycobacteria followed by topical application of
      hapten solution and irradiation with UVA. Unequivocal skin reactions were
      subsequently elicited with UVA exposure in the absence of hapten application.
      This enhanced UVA reactivity persisted and could be elicited for more than 2
      years. In these guinea pigs, remarkably increased sensitivity to UVB was also
      observed. These animals appear quite similar to persistent light reactors among
      humans. Muramyl dipeptide used in place of Mycobacteria was also found to be
      effective in inducing photosensitivity to UVA. There were great differences of
      reactivity noted among different strains of guinea pig, suggesting that
      persistent photosensitivity is influenced by genetic background. Enhanced UV
      sensitivity was induced without hapten application, only with injections of
      adjuvant and UVA irradiation in the immunization procedure. These results suggest
      that this model will be useful to study chronic actinic dermatitis.

PMID- 7727352
TI  - CD4+ T lymphocyte infiltration correlates with regression of a UV-induced
      squamous cell carcinoma.
AB  - It is currently unknown which arm of the immune system is responsible for
      regression of tumours. We have studied the T lymphocytes infiltrating a
      spontaneously regressing murine squamous cell carcinoma during the growth,
      plateau and regression phases of tumour development. In the plateau phase, where
      tumour growth is partially controlled by the immune system so that tumour size
      remains static, there was a considerable influx of CD4+ cells into the tumour.
      There was also an increase in the number of cells expressing the receptor for
      interleukin 2 (IL-2R), indicating that these cells were probably activated. The
      number of CD4+ cells remained high during the regression phase, where
      immunological destruction exceeded tumour growth. In contrast, CD8+ cells were
      only present in low numbers, and did not change during growth or regression of
      the tumours. These results indicate that CD4+ cells are probably responsible for
      tumour destruction. Thus CD4+ T lymphocytes are able to mediate tumour rejection
      and should be given more consideration for immunotherapy.

PMID- 7727353
TI  - Rearrangement of S-100 immunoreactive Langerhans' cells in human psoriatic skin
      treated with peptide T.
AB  - Dendritic cells marked by protein S-100 (S-100) antiserum in the suprabasal
      layers of the epidermis have previously been identified to be Langerhans' cells.
      In this study, S-100 immunoreactive cells have been investigated in psoriatic
      lesioned skin during and after peptide T treatment. Peptide T is an octapeptide
      with affinity for the CD4 receptor. Nine patients were intravenously infused with
      peptide T, 2 mg in 500 ml saline per day for 28 days. Sections from involved skin
      before, every week during, and after the treatment were processed by indirect
      immunofluorescence using S-100 antiserum. Before the treatment the epidermal
      Langerhans' cells were numerically decreased or even completely gone in the
      involved skin of psoriasis as compared to skin from normal healthy controls,
      while the dermal dendritic cells instead were increased and gathered in cell
      clusters around vascular structures. Four of the nine patients had
      histopathological improvements after the peptide T treatment, and, in those
      cases, the dendritic cells in the dermis were reduced in number, and the
      Langerhans' cells in the epidermis were numerically increased as well as even
      reversed to normal position and morphology. These changes in the distribution and
      density of Langerhans' cells represent their rearrangement during the course of
      psoriasis and/or the remission after peptide T treatment.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7727354
TI  - In vivo and in vitro dermal absorption of benzo[a]pyrene in rat, guinea pig,
      human and tissue-cultured skin.
AB  - Cross-species in vitro dermal absorption tests were conducted with 14C-labelled
      benzo[a]pyrene dissolved in acetone and applied to dermatomed skin (0.5 mm
      thickness) at comparable dose rates (8-13 micrograms/cm2). Skin absorption was
      determined using the Bronaugh in vitro flow-through procedure. The percentage (%)
      dermal absorption included the % 14C-activity detected persisting in the skin
      added to that detected in the receiver solution. Listed in decreasing order,
      total % in vitro dermal absorption obtained by 48 h postexposure was: 95 +/- 9.6%
      (rat), 51 +/- 3.0% (hairless guinea pig), 43 +/- 8.7% (human; 50-year-old), 34 +/
      12.4% (Testskin) and 23 +/- 5.3% (human; 32-year-old). Comparative in vivo
      studies demonstrated urinary recovery of 8 +/- 1.8% and 25 +/- 5.0% for rats
      (dose rate: 6 micrograms/cm2) and hairless guinea pigs (dose rate: 9
      micrograms/cm2), respectively. Total faecal recovery was 61 +/- 6.0% and 43 +/-
      6.1% for rats and guinea pigs, respectively. Necropsies conducted at 14 days
      postexposure demonstrated total 14C-activity tissue recoveries of 0.5 +/- 0.13%
      and 0.6 +/- 0.17% in rats and guinea pigs, respectively. Including the 14C
      activity extracted from the skin removed from the dose site at 14 days
      postexposure, the total % in vivo dermal absorbtion was 70 +/- 7.6% and 68 +/-
      9.3% for rats and guinea pigs, respectively. In summary, the in vitro data was
      consistent with the in vivo data in demonstrating that 14C-benzo[a]pyrene was
      well absorbed through skin.

PMID- 7727355
TI  - Effect of donor age on the phosphorylation of the retinoblastoma gene product in
      cultured human keratinocytes.
AB  - The retinoblastoma gene product (pRB) is a tumor suppressor protein. Recently, it
      has been shown that the phosphorylation of pRB is necessary for progression from
      G1 to S phase in a variety of cells. In a word, the phosphorylation of pRB
      accelerates cell growth. In this study, we examined the phosphorylation status of
      pRB in normal human keratinocytes obtained from donors aged from 1 year to 71
      years. The cells of old donors (61-71 years old) presented the more dense
      hypophosphorylated pRB band than cells of young donors (1-19 years old).
      Densitometric measurement showed that 42.3% +/- 4.8% of the total pRB was
      hypophosphorylated in cells of young donors, while 58.1% +/- 6.9% was
      hypophosphorylated in those of old donors. Results indicate that more pRB is
      hypophosphorylated in cells of old donors. The phosphorylated status of pRB might
      be related to the loss of growth fraction in human keratinocytes of old donors.

PMID- 7727356
TI  - Adjuvant-induced persistent photosensitivity models in guinea pigs. II.
      Characterization of immunological mechanisms.
AB  - The immunological characteristics of our adjuvant-induced persistent
      photosensitivity (AIPP) guinea pig model were examined. The sensitivity to long
      wavelength ultraviolet light (UVA) was transferred with peritoneal exudate cells.
      Proliferative response was observed in peritoneal exudate cells and lymph node
      cells concomitantly cultured in the presence of sera that had previously been
      irradiated with UVA. Cervical lymph nodes of AIPP animals were found to be
      hypertrophic, and the ratio of major histocompatibility complex (MHC) class II
      positive cells was increased as compared to that of intact guinea pigs. These
      results suggest that persistent photosensitivity elicited with UVA is based on
      cellular autoimmunity. Thus, the AIPP guinea pig model should be useful to study
      the mechanism of persistent photosensitivity disease in humans.

PMID- 7727357
TI  - Vessel hyalinization phenomenon in the laser treatment of tuberous hemangiomas
      and port wine stains.

PMID- 7727358
TI  - Three-dimensional structure in solution of neurotoxin III from the sea anemone
      Anemonia sulcata.
AB  - The three-dimensional structure in aqueous solution of the 27-residue polypeptide
      neurotoxin Anemonia sulcata toxin III (ATX III) has been determined from 1H NMR
      data. As ATX III self-associates in the millimolar concentration range, causing a
      marked concentration dependence for the chemical shifts of several residues
      [Norton, R. S., Cross, K., Braach-Maksvytis, V., & Wachter, E. (1993) Biochem. J.
      293, 545-551], it was necessary to record NOESY spectra over a range of
      concentrations in order to eliminate any intermolecular interactions from the NOE
      restraint set. The pairings of the six half-cystine residues were also unknown
      and had to be determined (as 3-17, 4-11, and 6-22) from preliminary structure
      calculations performed using both upper bound distance restraints from NOESY data
      and a substantial number of lower bound restraints inferred from the absence of
      NOESY cross-peaks. Final structures were determined, using the program X-PLOR,
      from interproton distance restraints inferred from NOEs, backbone and side chain
      dihedral angle restraints from spin-spin coupling measurements, and a smaller
      number of lower bound restraints. Stereospecific assignments for 11 beta
      methylene pairs were also included. The final set of 28 structures had an average
      pairwise RMS difference of 1.32 A over the backbone heavy atoms (N, C alpha, and
      C) and 2.18 A over all heavy atoms. For the well-defined region encompassing
      residues 3-22, the corresponding values were 0.62 and 1.28 A, respectively. ATX
      III adopts a compact structure containing four reverse turns (a distorted type I
      beta-turn at residues 6-9, a type I beta-turn at residues 8-11, and inverse gamma
      turns at residues 12-14 and 15-17) and two other chain reversals, but no regular
      alpha-helix or beta-sheet. Several of the residues most affected by aggregation
      are located on the surface of the molecule, forming a hydrophobic patch which may
      constitute part of the sodium channel binding surface. Possible relationships
      between the structure of ATX III and those of other sea anemone toxins that
      interact with the same site on the voltage-gated sodium channel are considered.

PMID- 7727359
TI  - Analysis of protein S C4b-binding protein interactions by homology modeling and
      inhibitory antibodies.
AB  - A monoclonal antibody (mAb 6F6) directed against the beta-chain of C4b-binding
      protein (C4BP) was previously shown to inhibit the binding of protein S to C4BP.
      To localize the epitope of this antibody, 23 overlapping synthetic peptides (15
      mers) covering the entire sequence (1-235) of the beta-chain of C4BP were used.
      When the immobilized peptides were screened for their ability to bind mAb 6F6,
      only peptide beta(51-65) showed high-affinity binding. The apparent affinity of
      mAb 6F6 for immobilized peptide beta(51-65) was somewhat similar to that for
      native C4BP with Kd approximately 1 nM for C4BP and approximately 9 nM for
      peptide beta(51-65). Peptide beta(51-65) inhibited the binding of the mAb 6F6 to
      immobilized C4BP with half-maximal inhibition at 30 microM peptide. Clotting
      assays of protein S anticoagulant cofactor activity using a factor Xa-1-stage
      assay with activated protein C allow measurement of free protein S in solution
      since only free protein S is active. Studies using such clotting assays showed
      that preincubation of C4BP with either mAb 6F6 or polyclonal anti-beta(31-45)
      antibodies inhibited the formation of the complex between C4BP and protein S.
      Previous studies showed that, although peptide beta(51-65) itself does not
      inhibit complex formation, peptide beta(31-45) does bind directly to protein S
      and does inhibit protein S binding to C4BP. The three-dimensional structure of
      the first SCR (residues 2-60) of the C4BP beta-chain was made on the basis of
      homology modeling.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727360
TI  - Homo- and heteronuclear two-dimensional NMR studies of the globular domain of
      histone H1: full assignment, tertiary structure, and comparison with the globular
      domain of histone H5.
AB  - The globular domain of chicken histone H1 (GH1) has been studied by 1H
      homonuclear and 1H-15N heteronuclear 2D NMR spectroscopy. After the full
      assignment of the proton and 15N resonances, the tertiary structure of GH1 was
      determined by an iterative procedure using distance geometry and restrained
      simulated annealing. The secondary structure elements of GH1, three helices (S5
      A16, S24-A34, N42-K56) followed by a beta-hairpin (L59-L73), are folded in a
      manner very similar to the corresponding parts of the globular domain of chicken
      histone H5 (GH5) [Clore et al. (1987) EMBO J. 6, 1833-1842; Ramakrishnan et al.
      (1993) Nature 362, 219-223]. However, subtle differences are detected between the
      two structures and between the electrostatic potentials surrounding the
      molecules. The most important differences are located in the loop between the
      second and third helices, a region that could be responsible for the different
      affinity for DNA. The most positively charged regions are not found in exactly
      the same position in GH1 and GH5. Nevertheless, their location seems to agree
      with the model where nucleosome binding takes place through contact points
      located at one DNA terminus and close to the dyad axis of the nucleosome [Schwabe
      & Travers (1993) Curr. Biol. 3, 628-630].

PMID- 7727361
TI  - Solution structure of a low molecular weight protein tyrosine phosphatase.
AB  - Protein tyrosine phosphatases (PTPs) are important enzymes involved in signal
      transduction, cell cycle regulation, and the control of differentiation. Despite
      the importance of this class of enzymes in the control of critical cell
      processes, very little structural information is available for this family of
      proteins. In this paper, we present the first solution structure of a protein
      tyrosine phosphatase. This protein is a low molecular weight cytosolic PTP that
      was initially isolated from bovine heart. The structure that was determined from
      1747 NMR-derived restraints consists of a central four-stranded parallel beta
      sheet surrounded by four alpha-helices and a short 3(10) helix. The phosphate
      binding site, identified by chemical shift changes upon the addition of the
      competitive inhibitors phosphate and vanadate, is in a loop region connecting the
      C-terminal end of the first beta-strand with the first alpha-helix. Residues in
      the second, fourth, and fifth alpha-helices and in some of the loop regions
      connecting the elements of regular secondary structure also contribute to the
      binding site. The structure determined here is consistent with previous
      mutagenesis and chemical modification studies conducted on this protein.

PMID- 7727362
TI  - 2.8-A structure of yeast serine carboxypeptidase.
AB  - The structure of monomeric serine carboxypeptidase from Saccharomyces cerevisiae
      (CPD-Y), deglycosylated by an efficient new procedure, has been determined by
      multiple isomorphous replacement and crystallographic refinement. The model
      contains 3333 non-hydrogen atoms, all 421 amino acids, 3 of 4 carbohydrate
      residues, 5 disulfide bridges, and 38 water molecules. The standard
      crystallographic R-factor is 0.162 for 10,909 reflections observed between 20.0-
      and 2.8-A resolution. The model has rms deviations from ideality of 0.016 A for
      bond lengths and 2.7 degrees for bond angles and from restrained thermal
      parameters of 7.9 A2. CPD-Y, which exhibits a preference for hydrophobic
      peptides, is distantly related to dimeric wheat serine carboxypeptidase II (CPD
      WII), which has a preference for basic peptides. Comparison of the two structures
      suggests that substitution of hydrophobic residues in CPD-Y for negatively
      charged residues in CPD-WII in the binding site is largely responsible for this
      difference. Catalytic residues are in essentially identical configurations in the
      two molecules, including strained main-chain conformational angles for three
      active site residues (Ser 146, Gly 52, and Gly 53) and an unusual hydrogen bond
      between the carboxyl groups of Glu 145 and Glu 65. The binding of an inhibitor,
      benzylsuccinic acid, suggests that the C-terminal carboxylate binding site for
      peptide substrates is Asn 51, Gly 52, Glu 145, and His 397 and that the "oxyanion
      hole" consists of the amides of Gly 53 and Tyr 147. A surprising result of the
      study is that the domains consisting of residues 180-317, which form a largely
      alpha-helical insertion into the highly conserved cores surrounding the active
      site, are quite different structurally in the two molecules. It is suggested that
      these domains have evolved much more rapidly than other parts of the molecule and
      are involved in substrate recognition.

PMID- 7727363
TI  - The activity of carboxypeptidase Y toward substrates with basic P1 amino acid
      residues is drastically increased by mutational replacement of leucine 178.
AB  - A random mutagenesis study on carboxypeptidase Y has previously suggested that
      Leu178 is situated in the S1 binding pocket, and this has later been confirmed by
      the three-dimensional structure. We here report the mutational replacement of
      Leu178 with Trp, Phe, Ala, Ser, Cys, Asn, Asp, or Lys and the kinetic
      characterization of each mutant, using substrates systematically varied at the P1
      position. The general effect of these substitutions is a reduced kcat/Km for
      substrates with uncharged amino acid residues in the P1 position, little effect
      on those with acidic residues, and an increased kcat/Km for those with basic
      amino acid residues. There is a clear correlation between the reduction in
      kcat/Km for substrates with uncharged P1 side chains and the nature of the
      residue at position 178. A small reduction is observed when Leu178 is replaced by
      another hydrophobic amino acid residue, a larger reduction when it is replaced by
      a polar residue, and a very large reduction when it is replaced by a charged
      residue. When Leu178 is replaced by Asp, kcat/Km is reduced by a factor of 2200
      for a substrate with Val in the P1 position. The kcat/Km values for the
      hydrolysis of substrates with charged P1 side chains are increased when Leu178 is
      replaced by an amino acid residue with the opposite charge, and they are
      decreased when it is replaced by a residue with the same charge. Surprisingly,
      all mutants (except L178K) exhibit increased activity with substrates with basic
      P1 side chains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727365
TI  - Primary and NMR three-dimensional structure determination of a novel crustacean
      toxin from the venom of the scorpion Centruroides limpidus limpidus Karsch.
AB  - A crustacean-specific toxin from the Mexican scorpion Centruroides limpidus
      limpidus was purified, and its primary sequence was determined, including
      disulfide bonds. This toxin has 66 amino acid residues and is stabilized by four
      disulfide bridges (Cys12-Cys65, Cys16-Cys41, Cys25-Cys46, and Cys29-Cys48). A
      detailed nuclear magnetic resonance structure of this protein was obtained using
      a combination of two-dimensional proton NMR experiments. The NMR parameters that
      gave 69 dihedral restraints and 418 distance constraints were used in molecular
      dynamics calculations in order to determine the solution conformation of the
      toxin. It is composed of a short alpha-helix and a three-stranded antiparallel
      beta-sheet. Although the regular secondary structure of this crustacean toxin is
      common to the structural motif of other scorpion toxins, detailed conformational
      analysis was performed in order to highlight structural features that might be
      responsible for the differential modulation of the toxin on sodium channels of
      distinct tissues: mammalian versus crustacean.

PMID- 7727364
TI  - Structure of the complex of L-benzylsuccinate with wheat serine carboxypeptidase
      II at 2.0-A resolution.
AB  - The structure of the complex of L-benzylsuccinate (Ki = 0.2 mM) bound to wheat
      serine carboxypeptidase II has been analyzed at 2.0-A resolution for native and
      inhibited crystals at -170 degrees C. The model has been refined and has a
      standard crystallographic R-factor of 0.176 for 57,734 reflections observed
      between 20.0- and 2.0-A resolution. The root mean square deviation from ideal
      bonds is 0.017 A and from ideal angles is 2.6 degrees. The model consists of 400
      amino acids, 4 N-linked saccharide residues, and 430 water molecules. L
      Benzylsuccinate occupies a narrow slot in the active site defined by Tyr 60, Tyr
      239, and the polypeptide backbone. One carboxylate forms hydrogen bonds to Glu
      145, Asn 51, the amide of Gly 52, and the catalytic His 397, suggestive of how
      the peptide C-terminal carboxylate is recognized by the enzyme. The phenyl ring
      stacks between Tyr 239 and Tyr 60, while the other carboxylate occupies the
      "oxyanion hole". One of the oxygens accepts hydrogen bonds from the amides of Tyr
      147 and Gly 53, while the other forms a very close contact (2.3 A) with the O
      gamma of Ser 146, forcing the side chain into a conformation alternative to that
      found in the resting state of the enzyme. The inhibitor occupies the active site
      in a way that suggests that it can be regarded as a transition-state analogue of
      serine carboxypeptidases. The model suggests a novel enzymatic mechanism,
      involving substrate-assisted catalysis, that might account for the low pH optimum
      (4.0-5.5) of peptidase activity unique to this family of serine proteinases.

PMID- 7727366
TI  - Membrane location of spin-labeled apocytochrome c and cytochrome c determined by
      paramagnetic relaxation agents.
AB  - The mitochondrial precursor protein horse heart apocytochrome c was spin-labeled
      on the cysteine residue at position 14 or 17 in the N-terminal region, and the
      mature protein yeast cytochrome c was similarly labeled on the single free
      cysteine residue at position 102 at the C-terminal. The proteins were bound to
      negatively charged phospholipid bilayers, and the accessibility of the spin
      labeled cysteine residues to lipid-soluble molecular oxygen and to the lipid
      impermeant chromium oxalate anion was determined from the saturation properties
      of the ESR spectra. Binding of the protein was found to have a considerable
      effect on the local oxygen concentrations within the lipid bilayer. The
      accessibilities of the spin-labeled proteins relative to those obtained for
      phospholipids spin-labeled either in the headgroup or at positions in the sn-2
      acyl chain, in the presence of unlabeled protein, identify the position of the
      spin-labeled cysteine residues in the phospholipid bilayer. The spin label on
      apocytochrome c bound to phosphatidylglycerol bilayers lies between the 5- and 14
      C positions of the lipid acyl chain. Admixture of > or = 75 mol %
      phosphatidylcholine induces an additional surface-associated apocytochrome c
      population. The spin label on native and heat-denatured cytochrome c is located
      at the membrane surface. These different extents of membrane penetration
      correlate also with the reduction in local oxygen concentration experienced by
      spin-labeled phospholipids on binding of apo- and holocytochrome c. The possible
      biological implications of the data are discussed.

PMID- 7727367
TI  - Conformational properties of four peptides corresponding to alpha-helical regions
      of Rhodospirillum cytochrome c2 and bovine calcium binding protein.
AB  - Four peptides corresponding to alpha-helical regions delimited by residues 63-73
      and 97-112 of cytochrome c2 (Rhodospirillum) and residues 24-36 and 45-55 of
      bovine calcium binding protein are predicted to be alpha-helical by a recently
      developed method [Rooman, M., Kocher, J.P., & Wodak, S.J. (1991) J. Mol. Biol.
      221, 961-979], synthesized by solid phase methods, and purified by HPLC, and
      their solution conformations are determined by NMR and CD. The observed
      conformational properties of these peptides in solution confirmed prediction
      results: in water/TFE (60/40, v/v) at room temperature, these peptides adopt an
      alpha-helical conformation, as shown by an extended pattern of strong, sequential
      dNN(i,i + 1) NOE cross-peaks, d alpha N(i,i + 1) NOEs of reduced intensity,
      several medium-range [d alpha N(i,i + 3), d alpha N(i,i + 4), d alpha beta-(i,i +
      3)] NOE connectivities, small 3JH alpha N values, and more upfield alpha-proton
      chemical shifts. CD studies at different TFE concentrations and at room
      temperature provide further evidence of the propensity of these peptides to adopt
      an alpha-helical conformation in solution, as determined by the ellipticity
      values at 222 nm, and by deconvolution of the CD spectra. According to the method
      used, helicities in the range 34-50% and 55-75% are found for the 63-73 and 97
      112 fragments of cytochrome c2, respectively, and in the range 53-80% and 42-65%
      for the fragments 24-36 and 45-55 of calcium binding protein in water/TFE (60/40,
      v/v) at 298 K. In addition, the experiments and predictions agree for those
      residues that are more flexible. Finally, the relevance of our results for the
      protein folding pathways is discussed.

PMID- 7727368
TI  - Conformation of a peptide corresponding to T4 lysozyme residues 59-81 by NMR and
      CD spectroscopy.
AB  - The conformation, in solution, of a peptide corresponding to residues 59-81 from
      T4 lysozyme [LYS(59-81)] has been determined by 1H NMR and CD spectroscopy. This
      peptide spans the region corresponding to helix C in the crystal structure of T4
      lysozyme. Secondary structure predictions indicated that the peptide would
      possibly be helical in an aqueous environment, but in a more hydrophobic
      environment the peptide would certainly adopt a helical conformation. This
      prediction was confirmed by the far-UV CD and NMR studies, which showed the
      peptide to be relatively unstructured in aqueous solution and significantly
      helical in the presence of either TFE or SDS micelles, although the 1H NMR
      results did give some indication of the presence of nascent helix in aqueous
      solution. For LYS(59-81), in TFE, the three-dimensional structure derived from
      the NMR data showed that the helix had a more pronounced curvature than the
      gradual bend observed in the crystal structure.

PMID- 7727369
TI  - Interactions of nucleotides with fully unadenylylated glutamine synthetase from
      Salmonella typhimurium.
AB  - Glutamine synthetase (GS) catalyzes the ATP-dependent biosynthesis of glutamine
      from glutamate and ammonia in the presence of divalent cations. To gain insight
      into the structural basis of the feedback inhibition of GS by AMP, we have
      studied crystal structures of GS complexes with AMP and the related molecules:
      AMPPNP (a less hydrolyzable ATP analog), ADP, GDP, adenosine, and adenine. AMP is
      a feedback inhibitor of GS; ATP and ADP are cofactors, and AMPPNP, GDP,
      adenosine, and adenine are also GS inhibitors. GS used in this study is from
      Salmonella typhimurium and is free of covalent modification by adenylylation. All
      of the crystals examined contain two bound MN2+ ions per GS subunit. The X-ray
      structures show that all nucleotides bind at the same site, the cofactor ATP
      binding site, as do adenosine and adenine. Thus from X-ray structures, AMP,
      adenosine, adenine, and GDP would be expected to inhibit GS-Mn by competing with
      the substrate ATP for the active site. This suggestion from the crystal
      structures that AMP is competitive with respect to ATP is supported by kinetic
      measurements using the biosynthetic assay.

PMID- 7727370
TI  - The A-state of barnase.
AB  - The acid-induced denaturation of barnase and its mutants has been analyzed to
      search for partly-folded intermediates. Differential scanning calorimetry of
      barnase deviates from two-state behavior below pH 4.0 at low ionic strength, with
      the maximum discrepancy at pH 2.7. Addition of 200 mM KCl apparently restores the
      two-state transitions. Thermograms of barnase mutants at pH 2.7 and low ionic
      strength fall into three classes: alpha, symmetric transitions which fit well to
      a two-state equilibrium; b, asymmetric transitions indicating deviation from two
      state behavior; and c, transitions with an obvious second component. The most
      distorted thermograms are observed for mutants that had previously been
      engineered to accumulate at equilibrium the major kinetic folding intermediate
      state of barnase at neutral pH. Further analysis of these mutants show the
      existence of complex equilibria on thermal denaturation. Addition of KCl leads to
      the slow formation of soluble aggregated forms (A-state) which share some of the
      properties of the "molten globule" state, i.e., significant secondary structure,
      lack of fixed tertiary structure, and solvent-accessible hydrophobic patches. The
      far-UV CD spectrum of the A-state can be explained in terms of native-like
      secondary structure contributions. Kinetic and chemical cross-linking experiments
      show that dimerization of partly-folded molecules occurs in the transition
      region, and such dimerization is probably the rate-limiting step in the formation
      of the A-state in the presence of KCl. As the A-state has been observed clearly
      so far for only the mutants in which the folding intermediate has been designed
      to accumulate, we suggest that the A-state would be related to the main folding
      intermediate state of barnase. The intermediate would be highly stabilized at low
      pH, and it is prone to self-associate in these conditions.

PMID- 7727371
TI  - Ultrafast energy transfer in FMO trimers from the green bacterium Chlorobium
      tepidum.
AB  - Time-resolved absorption difference profiles were obtained for FMO trimers,
      isolated from the green thermophilic bacterium Chlorobium tepidum, using one- and
      two-color femtosecond pump-probe techniques. Uphill and downhill energy transfers
      between inequivalent pigments in this antenna contribute to lifetime components
      that range from approximately 100 to approximately 900 fs in the isotropic
      absorption difference signals, depending on the pump and probe wavelengths.
      Vibrational thermalization of BChl a pigments may also influence the kinetics.
      The major lifetime components in the anisotropy decays at most wavelengths are 75
      135 fs and 1.4-2.0 ps. The slower anisotropy decays probably stem from
      equilibration among equivalent, lowest-energy pigments belonging to different
      subunits in the trimer. The initial anisotropy r(0) is appreciably larger than
      0.4 at several wavelengths, but r(t) typically decays to a value less than 0.4
      within approximately 100 fs.

PMID- 7727372
TI  - Conformational gating of the dissimilatory sulfite reductase from Desulfovibrio
      vulgaris (Hildenborough). Synthesis, characterization, and stopped-flow kinetics
      studies of 1,5-IAEDANS-labeled desulfoviridin.
AB  - The siroheme prosthetic center in the dissimilatory sulfite reductase
      (desulfoviridin) from Desulfovibrio vulgaris (Hildenborough) readily binds
      exogenous ligands in the reduced state, but it does not do so in the oxidized
      state. In contrast, free oxidized siroheme in solution is observed to bind
      ligands rapidly. This can only be explained by a structural barrier that
      precludes ligand binding to the enzyme in the oxidized state but is removed after
      reduction. These observations suggest a redox-linked structural transformation
      that provides a gating mechanism for enzyme activation. The rate constants
      defining these structural perturbations, from oxidized-->reduced and reduced-
      >oxidized states, have been determined by monitoring changes in both the natural
      emission from desulfoviridin and the emission from a surface-bound fluorophore
      (1,5-IAEDANS). Consistent results were obtained from these two independent
      experimental measurements (at 25 degrees C: kox-->red approximately 8 s-1, kred-
      >ox approximately 0.05 s-1). Activation energies for each transition have been
      determined from Arrhenius plots (ox-->red: delta G* 16.5 kcal mol-1, delta H* 3.5
      kcal mol-1, delta S* -43.8 cal K-1 mol-1; red-->ox: delta G* 19.2 kcal mol-1,
      delta H* 11.3 kcal mol-1, delta S* -26.6 cal K-1 mol-1). These data are used to
      further develop a functional model previously proposed for this class of enzyme
      [Lui, S. M., Soriano, A., & Cowan, J. A. (1993) J. Am. Chem. Soc. 115, 10483;
      Lui, S. M., Liang, W., Soriano, A., & Cowan, J. A. (1994) J. Am. Chem. Soc. 116,
      4531].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727373
TI  - Anaerobic pathway for conversion of the methyl group of aromatic methyl ethers to
      acetic acid by Clostridium thermoaceticum.
AB  - Clostridium thermoaceticum and other anaerobic acetogenic bacteria can utilize
      the methyl group of aromatic methyl ethers as a carbon and energy source. It has
      been unclear what pathway is used to metabolize this methyl group. In the work
      reported here, the pathway was established by identifying and quantitating the
      substrates, stable intermediates, and products of O-demethylation of syringic
      acid. By measuring the dependence of the O-demethylation reaction on purified
      enzymes of the acetyl-CoA pathway, it was established that CO dehydrogenase, the
      corrinoid/iron-sulfur protein, and methyltransferase all were required for acetyl
      CoA formation. By 13C-NMR spectroscopy it was shown that the O-demethylase from
      C. thermoaceticum converts the methyl group of syringate to
      methyltetrahydrofolate (CH3-H4folate). When the reaction was conducted in the
      presence of CO, H2, or titanium(III), or in the absence of any electron donor,
      the rate of demethylation of syringic acid at pH 7.2 was approximately 15 nmol
      min-1 mg-1. In the absence of CO, CH3-H4folate accumulated as a stable product.
      When CO was added, 13CH3-H4folate was converted to [2-13C]acetyl-CoA, [2
      13C]acetyl phosphate, and [2-13C]acetate. Therefore, the acetogenic O-demethylase
      uses H4folate as acceptor of the methyl group of phenyl methyl ethers and
      catalyzes the formation of CH3-H4folate. The pathway of conversion of CH3
      H4folate, CO, and CoA to acetyl-CoA has been studied previously.
      Methyltransferase catalyzes the reaction of CH3-H4folate with the corrinoid/iron
      sulfur protein to form a methylcobalt species. The nickel/iron-sulfur enzyme CO
      dehydrogenase then catalyzes the final steps in the formation of acetyl
      CoA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727374
TI  - Kinetics of folding of guanidine-denatured hen egg white lysozyme and
      carboxymethyl(Cys6,Cys127)-lysozyme: a stopped-flow absorbance and fluorescence
      study.
AB  - The folding kinetics of hen egg white lysozyme and of a three-disulfide
      derivative of lysozyme [carboxymethyl(Cys6,Cys127)-hen egg white lysozyme] have
      been studied by absorbance- and fluorescence-detected stopped-flow techniques. A
      "very-fast" phase with a time constant in the millisecond range has been observed
      by both absorbance and fluorescence when unfolded lysozyme in 4 M guanidine
      hydrochloride, 100 mM phosphate buffer, and pH 2.0 is refolded at 0.5 M guanidine
      hydrochloride, 100 mM phosphate, and pH 6.7. Data obtained from fluorescence
      detected refolding studies show that a transient intermediate is formed during
      the very-fast refolding phase. This intermediate is characterized by substantial
      quenching of tryptophan fluorescence. In addition, analysis of the fluorescence
      data indicates the presence of an additional "burst" phase that occurs within the
      dead time of the instrument, < 3 ms. The very-fast phase is not observed during
      the refolding of the three-disulfide derivative. In addition, the three-disulfide
      derivative re-attains the final native folded conformation more rapidly than the
      unmodified protein over the range of temperatures studied (10-20 degrees C). We
      conclude that, not only does the presence of the disulfide bond between Cys6 and
      Cys127 slow down the overall folding process of lysozyme, but it also directs the
      folding of lysozyme through a pathway characterized by a non-native tertiary
      interaction(s).

PMID- 7727375
TI  - Structural requirements for addition of O-linked carbohydrate to recombinant
      erythropoietin.
AB  - To define the structural requirements for addition of O-linked glycosylation in
      vivo, recombinant erythropoietin (rEPO) variants were constructed. Thirty-three
      independent Ser or Thr substitutions were constructed and examined to see which
      were subject to O-linked carbohydrate addition. Variants with Thr mutations at
      positions 123 and 125, but not elsewhere, contained additional carbohydrate,
      which suggests that several positions around the existing O-linked glycosylation
      site (Ser126), but not elsewhere, contain the necessary information for O-linked
      carbohydrate addition. Two forms of the Thr125 variant were identified. One form
      was glycosylated only at residue 125, and a second form was glycosylated at both
      Thr125 and Ser126, the normal O-glycosylation site. We have also found that
      glycosylation is less efficient when rEPO is improperly folded and that prolines
      at -1 and +1 relative to the O-glycosylation site enhance glycosylation.

PMID- 7727376
TI  - Induction of G protein-independent agonist high-affinity binding sites of D-1
      dopamine receptors by beta-mercaptoethanol.
AB  - We have purified the D-1 dopamine receptor 8200-fold to 78% purity from rat
      striatal membranes. Critical to this purification was the N-ethylmaleimide (NEM)
      mediated alkylation of all endogenous sulfhydryl groups, except those associated
      with the D-1 dopamine receptors, which were protected by the D-1 agonist SKF R
      38393. Such NEM treatment of D-1 receptors abolished all agonist high-affinity
      binding sites of the receptors, but did not alter the antagonist binding
      properties. When NEM-treated D-1 receptors were affinity-purified by mercury
      agarose columns, the pharmacological properties of these purified receptors were
      examined, after removal of beta-mercaptoethanol (beta ME), which was used for
      elution of receptors from the affinity column. Purified D-1 receptors displayed
      typical dopaminergic antagonist binding values; however, agonists bound to the
      purified receptors with only high-affinity binding values, despite the prior
      absence of high-affinity sites in crude soluble extracts of NEM-treated
      receptors. The agonist high-affinity binding of purified D-1 receptors was
      insensitive to modulation by the GTP analog Gpp(NH)p and occurred in the absence
      of any G proteins. These Gpp(NH)p-insensitive high-affinity sites appeared to be
      induced by beta ME, since similar high-affinity binding was also restored by beta
      ME to crude soluble and membrane-bound receptors, which had been pretreated with
      NEM. The ability of D-1 dopamine receptors to bind with high-affinity to agonists
      in the absence of functionally active G proteins may be an intrinsic property of
      the reduced state of D-1 dopamine receptors.

PMID- 7727377
TI  - Protein kinase A induces phosphorylation of the human 5-HT1A receptor and
      augments its desensitization by protein kinase C in CHO-K1 cells.
AB  - Protein kinase C has been previously shown both to phosphorylate and to
      desensitize the ability of the human 5-HT1A receptor to inhibit adenylyl cyclase
      [Raymond, J. R. (1991) J. Biol. Chem. 266, 14747-14753]. In this study, we
      examined the effects of short-term treatment with protein kinase A activators on
      coupling to the inhibition of adenylyl cyclase and on phosphorylation of the
      human serotonin 5-HT1A receptor in CHO cells that stably express 1200 fmol of
      receptor/mg of protein. Forskolin induced a concentration- and time-dependent
      phosphorylation of the receptor that was detectable at 5 min and maximal at 15-30
      min with a half-maximal concentration of 10-20 microM. Phosphorylation was also
      induced by Sp-cAMPS or dibutyryl-cAMP, and blocked by Rp-cAMPS and a
      pseudosubstrate inhibitor of PKA, but not by heparin (inhibitor of receptor
      kinase) or sphingosine (inhibitor of PKC). The stoichiometry of phosphorylation
      induced by forskolin was 1 mol of phosphate per mole of receptor. PKA activators
      did not induce a measurable desensitization of 5-HT1A receptor-inhibited adenylyl
      cyclase activity. However, forskolin augmented the desensitization caused by a
      submaximal concentration of phorbol 12-myristate 13-acetate (300 nM PMA) as
      evidenced by a rightward shift of the concentration-response curve for 5-HT, and
      approximately doubled the amount of phosphate incorporated into the receptor by
      PMA. Forskolin did not augment desensitization or increase the degree of
      phosphorylation induced by a maximal concentration of PMA (5 microM).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7727378
TI  - Insulin-like compounds related to the amphioxus insulin-like peptide.
AB  - Three insulin-like compounds consisting of two disulfide-linked polypeptide
      chains have been synthesized. The A-chains of these compounds correspond either
      to the A- or to the A + D-domain of the putative amphioxus insulin-like peptide
      (amphioxus ILP), and their B-chains correspond either to the B-chain of insulin
      or to a slightly modified (i.e., [1-Thr]) B-domain of amphioxus ILP. The
      biological potency of these compounds was evaluated in mammalian cells or cell
      fractions containing either human or rat insulin receptors or human or mouse
      insulin-like growth factor I (IGF-I) receptors, with respect to binding affinity,
      insulin-like metabolic activity (lipogenesis), and growth factor activity
      (mitogenesis). Amphioxus ILP A/bovine insulin B and amphioxus ILP A + D/bovine
      insulin B exhibited potencies ranging from 2.0 to 9.8% relative to natural
      insulin, and both compounds were full agonists in lipogenesis assays, stimulating
      lipogenesis to the same maximal extent as seen with natural insulin. Amphioxus
      ILP A/amphioxus ILP [1-Thr]B stimulated lipogenesis with a potency of 0.01%
      relative to natural insulin. We consider this compound also likely to be a full
      agonist. In assays measuring binding to IGF-I receptors and stimulation of
      mitogenesis, these compounds displayed some activity although the activity was
      too low for exact quantification. These results suggest that amphioxus ILP has
      retained an overall structural similarity to mammalian insulin and IGF-I but has
      also accumulated substantial mutations which markedly reduce its ability to bind
      and activate their cognate receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727379
TI  - Extensively methylated myosin subfragment-1: examination of local structure,
      interactions with nucleotides and actin, and ligand-induced conformational
      changes.
AB  - The atomic structure of myosin subfragment-1 (S1) has been recently solved for
      crystals of extensively methylated S1 [Rayment et al. (1993) Science 261, 50-58].
      In this study, the effect of such a modification on S1 structure and function was
      examined. According to the far- and near-ultraviolet CD spectra, the methylation
      does not affect the secondary structure of S1 but causes limited changes in its
      tertiary structure. The methylation significantly decreases the affinity of S1
      for actin in rigor and, to a lesser degree, that of S1 to actin in the presence
      of MgATP gamma S. This modification, like the trinitrophenylation of Lys-83,
      accelerates the dissociation of a nucleotide trapped on S1 either by phosphate
      analogs or by cross-linking of the SH1 and SH2 thiols. Methylation strongly
      impairs the coupling between the actin- and nucleotide-binding sites as revealed
      by the reduced effect of actin on the release of epsilon ADP from the active
      site. It also causes a complete loss of in vitro motility of actin filaments over
      methylated HMM. In addition to this, methylation also impairs the communication
      between other sites on S1 including that between the nucleotide-binding site and
      SH1, and the actin-binding site and the 27/50 kDa junction and a site at 74 kDa
      from the N-terminus of S1. These changes are revealed in SH1 modification,
      thermolysin digestion, and vanadate-dependent photocleavage experiments,
      respectively. The increased rate of thermal denaturation of S1 and the loss of S1
      protection by ADP and actin from this process also indicate flawed communications
      in methylated S1. It is concluded that these relatively mild but numerous and
      important changes impair the function of methylated S1.

PMID- 7727380
TI  - The dimerization stability of the HLH-LZ transcription protein family is
      modulated by the leucine zippers: a CD and NMR study of TFEB and c-Myc.
AB  - In the HLH-LZ protein family, the helix-loop-helix DNA-binding dimerization
      domain is followed in the sequence by a leucine zipper motif. The precise
      function of this second dimerization domain is still unclear, since the HLH motif
      of a subset of this family has been shown to be necessary and sufficient for
      dimerization. However, deletion and mutagenesis studies of the leucine zipper in
      various HLH-LZ proteins have shown a clear influence of this motif on homo- and
      heterodimerization. In this paper, we present a structural characterization of
      synthetic peptides encompassing the leucine zipper sequences of c-Myc and TFEB,
      using circular dichroism, analytical ultracentrifugation, and nuclear magnetic
      resonance. We show that the different ability of the synthetic leucine zippers of
      c-Myc and TFEB to homodimerize at neutral pH reflects the different dimerization
      properties reported for the entire proteins. The TFEB protein is known to form
      homodimers. c-Myc, on the other hand, does not homodimerize in vivo, but is
      mostly found in heterodimeric complexes with Max, another protein of the HLH-LZ
      family. Accordingly, our results show that the TFEB peptide homodimerizes at
      neutral pH whereas the Myc peptide dimerizes to a comparable amount only at
      acidic pH and high ionic strength. Both synthetic peptides are far less stable
      than leucine zippers of the b-ZIP family. The relative stability of the two
      leucine zippers and the factors which stabilize the dimer formation are
      discussed.

PMID- 7727381
TI  - Structure and function of Escherichia coli DnaB protein: role of the N-terminal
      domain in helicase activity.
AB  - We have analyzed the contributions of specific domains of DnaB helicase to its
      quaternary structure and multienzyme activities. Highly purified tryptic
      fragments containing various domains of DnaB helicase were prepared. Fragment I
      lacks 14 amino acid (aa) residues from the N-terminal of DnaB helicase. Fragments
      II and III are 33-kDa C-terminal and 12-kDa N-terminal polypeptides,
      respectively, of fragment I. The single-stranded DNA-dependent ATPase and DNA
      helicase activities of DnaB helicase and its fragments were examined in detail.
      The ATPase activities of native DnaB helicase and fragment I were comparable;
      however, the ATPase activity of fragment II was somewhat diminished. Unlike the
      ATPase activity, the DNA helicase activity was totally abolished in fragment II
      and was not complemented by the addition of equimolar fragment III. Consequently,
      the N-terminal 17-kDa domain appeared to have an indispensable role in the DNA
      helicase action, but not in other enzymatic activities. Fragment I had a
      hexameric structure similar to that observed with DnaB helicase in both size
      exclusion HPLC (SE-HPLC) and chemical cross-linking studies. SE-HPLC analysis
      indicated that fragment II had an apparent hexameric form. However, a detailed
      chemical cross-linking analysis showed that it formed stable dimers but the
      formation of a stable hexamer was severely impaired. Thus, the N-terminal domain
      appeared to have a strong influence on the hexamer formation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7727382
TI  - Thermal activation of a group II intron ribozyme reveals multiple conformational
      states.
AB  - Conformational changes often accompany biological catalysis. Group II introns
      promote a variety of reactions in vitro that show an unusually sharp temperature
      dependence. This suggests that the chemical steps are accompanied by the
      conversion of a folded-but-inactive form to a differently folded active state. We
      report here the kinetic analysis of 5'-splice-junction hydrolysis (SJH) by
      E1:12345, a transcript containing the 5'-exon plus the first five of six intron
      secondary structure domains. The pseudo-first-order SJH reaction shows (1)
      activation by added KCl to 1.5 M; (2) cooperative activation by added MgCl2,
      nHill = 4.1-4.3, and [MgCl2]vmax/2 approximately 0.040 M; and (3) a rather high
      apparent activation energy, Ea approximately 50 kcal mol-l. In contrast, the 5'
      terminal phosphodiester bond of a domain 5 transcript (GGD5) was hydrolyzed with
      Ea approximately 30 kcal mol-1 under SJH conditions; the 5'-GG leader
      dinucleotide presumably lacks secondary structure constraints. The effect of
      adding the chaotropic salt tetraethylammonium chloride (TEA) was also
      investigated. TEA reduced the melting temperatures of GGD5 and E1:12345. TEA also
      shifted the profile of rate versus temperature for SJH by E1:12345 toward lower
      temperatures without affecting the maximum rate. TEA had little effect on the
      rate of hydrolysis of the 5'-phosphodiester bond of GGD5. The high apparent
      activation enthalpy and entropy for SJH along with the effect of TEA on these
      parameters imply that conversion of an inactive form of E1:12345 to an active
      conformation accompanies enhanced occupation of the transition state as the
      temperature is raised to that for maximum SJH. Analytical modeling indicates that
      either a two-state model (open and disordered, with open being active) or a three
      state model (compact, open, and disordered) could account for the temperature
      dependence of kSJH. However, the three-state model is clearly preferable, since
      it does not require that the activation parameters for phosphodiester bond
      hydrolysis exhibit exceptional values or that the rates for the chemical steps of
      SJH respond directly to TEA addition.

PMID- 7727383
TI  - A novel mutant topoisomerase II alpha present in VP-16-resistant human melanoma
      cell lines has a deletion of alanine 429.
AB  - The human melanoma cell line FEM-X was selected in multiple steps with VP-16
      (etoposide) and an inhibitor of P-glycoprotein (Campain et al., 1993). The
      resulting clones, FVP1b and FVP3, are highly resistant to the nonintercalative
      epipodophyllotoxins and exhibit moderate levels of resistance to doxorubicin. The
      topoisomerase II activity present in crude nuclear extracts from mutant and wild
      type cells is similar in amount and equally sensitive to VP-16. However, in live
      cells, the topoisomerase II from FVP1b and FVP3 is much less susceptible to drug
      induced cleavable complex formation than is that from FEM-X. Using reverse
      transcription followed by the polymerase chain reaction (RT-PCR), we have cloned
      and sequenced the entire cDNA for topoisomerase II alpha from FEM-X and FVP3. The
      only sequence change unique to the cDNA from drug-resistant cells is a 3 bp
      deletion of nucleotide 1320-1322, resulting in a deletion of Ala429. Three FEM-X
      sublines of increasing resistance were tested, and the prevalence of the mutant
      RNA over wild-type increases in these cells in parallel with their resistance to
      VP-16. In FVP3, the most highly resistant line, expression of the wild-type
      allele is barely detectable. Analysis of genomic DNA shows that FEM-X is
      homozygous for the wild-type topoisomerase II alpha sequence and that each of the
      drug-resistant clones possesses both wild-type and mutant alleles. Although not
      definitive, these genetic results suggest that the deletion of Ala429 from
      topoisomerase II alpha makes the enzyme less susceptible to drug-induced
      cleavable complex formation and confers a growth advantage upon cells in the
      presence of VP-16.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727384
TI  - Quinobenoxazines: a class of novel antitumor quinolones and potent mammalian DNA
      topoisomerase II catalytic inhibitors.
AB  - The antineoplastic quinobenoxazines A-62176 and A-74932 were shown to be potent
      inhibitors of mammalian DNA topoisomerase II in vivo. This was demonstrated by
      their selective inhibition of the SV40 DNA replication stages that require
      topoisomerase II. Neither drug stabilized a covalent complex of the enzyme with
      SV40 DNA, which suggests that they are not poisons of DNA topoisomerase II. A
      77601, an analog having little antitumor activity, barely inhibited DNA
      topoisomerase II in vivo, even at high concentrations. These findings were
      supported by in vitro studies which showed that A-62176 and A-74932, but not A
      77601, strongly inhibited the catalytic activity of mammalian DNA topoisomerase
      II. A-62176 did not cause topoisomerase II-mediated DNA strand breaks in vitro
      under conditions in which adriamycin produced extensive DNA breakage. The
      antineoplastic and topoisomerase inhibitory activities of the quinobenoxazines
      correlate with their ability to unwind DNA. A-62176 antagonized the poisoning of
      topoisomerase II by VM-26 in vivo and in vitro, but had no effect on DNA breakage
      induced by camptothecin, a DNA topoisomerase I poison. A-62176 and A-74932 thus
      inhibit DNA topoisomerase II reactions at a step prior to the formation of the
      "cleavable complex" intermediate. These findings indicate that stabilization of
      the DNA topoisomerase II-DNA cleavable complex is not necessary for the antitumor
      activity of this class of quinolones and that the catalytic inhibition of DNA
      topoisomerase II may contribute significantly to the anticancer activity of other
      DNA topoisomerase II inhibitors.

PMID- 7727385
TI  - Fluorescence-detected stopped flow with a pyrene labeled substrate reveals that
      guanosine facilitates docking of the 5' cleavage site into a high free energy
      binding mode in the Tetrahymena ribozyme.
AB  - Fluorescence-detected stopped flow kinetics are reported for binding of pyrene
      (pyr) labeled oligonucleotide substrates, pyrCUCUA and pyrCCUCUA, to the L-21
      ScaI ribozyme from Tetrahymena thermophila. Both oligomer substrates contain a UA
      sequence that mimics the cleavage site where pG attacks the self-splicing group I
      intron from which the ribozyme was derived. Kinetics were measured in the
      presence and absence of saturating 5'-monophosphate guanosine substrate (pG) at 5
      mM Mg2+ and 15 degrees C. In the absence of pG, binding of both oligonucleotide
      substrates is consistent with a one step mechanism involving only base pairing.
      Upon addition of pG, pyrCCUCUA is observed to bind in two steps: base pairing to
      the ribozyme to form the P1 helix and, presumably, subsequent docking of the P1
      helix into the catalytic core. A third transient is also observed, which likely
      includes the chemical step following docking. All rate constants are measured for
      this mechanism. Surprisingly, the equilibrium constant for docking, K2, is
      unfavorable in the absence of pG (K2 < 1) and only modestly favorable in the
      presence of pG (K2 = 4). These results contrast with those for a 5' exon mimic,
      pyrCCUCU, in which docking is strongly favored under the above conditions in the
      absence of pG; K2 = 100 [Bevilacqua, P. C., Kierzek, R., Johnson, K. A., &
      Turner, D. H. (1992) Science 258, 1355-1358]. These results suggest an
      unfavorable interaction between the ribozyme and the pA at the site of cleavage.
      Implications are discussed for the catalytic strategy of the ribozyme and for the
      self-splicing cascade that occurs in nature.

PMID- 7727386
TI  - Structural and functional consequences of a Glu L212-->Lys mutation in the QB
      binding site of the photosynthetic reaction center of Rhodopseudomonas viridis.
AB  - The properties of the quinone acceptor complex in the photosynthetic reaction
      center of the atrazine-resistant Rhodopseudomonas viridis mutant A2 (Glu L212-
      >Lys) were studied by EPR spectroscopy and by photoelectric measurements. The EPR
      signal attributed to the semiquinone-iron (QB-Fe2+) was significantly different
      from wild type and resembled that found in PS II. Essentially normal oscillations
      of QB-Fe2+ were observed upon flash illumination. The kinetics of the first and
      the second electron transfer from QA to QB were characterized by a photoelectric
      double-flash method. Compared to wild type, the rate of the first electron
      transfer in the large majority of reaction centers was decreased drastically from
      k1 = (18 microseconds)-1 in the wild type to (70 ms)-1 in the mutant, whereas the
      second electron transfer was only slightly slowed down with a rate of k2 = (260
      microseconds)-1 compared to (65 microseconds)-1 in wild type (pH 7). When the pH
      was raised above 10, in a major fraction of the reaction centers a fast kinetics
      of the first electron transfer, like that in wild type, reappeared. The
      experimental results are interpreted as an effect of the positive charge on the
      lysine causing a significant structural change of the QB binding pocket and a
      strongly diminished affinity for ubiquinone. The slow QA(-)-->QB electron
      transfer kinetics are thus attributed to ubiquinone binding, which is rate
      limiting. The possible role of the residue Glu L212, which is conserved in all
      purple bacteria, in electron and proton transfer to QB is discussed.

PMID- 7727387
TI  - Synthesis of oligodeoxynucleotides containing analogs of O6-methylguanine and
      reaction with O6-alkylguanine-DNA alkyltransferase.
AB  - O6-Alkylguanine-DNA alkyltransferase (AGT) repairs the mutagenic O6-methylguanine
      (O6-mG) lesion by transferring a methyl group from the 6-position of guanine to a
      cysteine residue on the protein. The simplest possible mechanism is an SN2
      process in which the cysteine displaces the methyl group off of the guanine in a
      concerted reaction. To probe the interactions between the protein and guanine
      leaving group, oligodeoxynucleotide duplexes containing analogs of O6mG were
      synthesized and then reacted with AGT. The analogs, which were incorporated into
      deoxynucleotides include O6-methylhypoxanthine (O6-mH),S6-methyl-6-thioguanine
      (S6mG),S6-methyl-6-thiohypoxanthine (S6mH),Se6-methyl-6-selenoguanine (Se6mG),Se6
      methyl-6-selenohypoxanthine (Se6mH), O6-methyl-1-deazaguanine (O6m1DG), O6-methyl
      3-deazaguanine (O6m3DG), and O6-methyl-7-deazaguanine (O6m7DG), differ from O6mG
      in that the heteroatoms have been replaced so that they are poorer hydrogen bond
      participants and proton acceptors. AGT was reacted with oligonucleotide duplexes
      of the sequence 5'-GGC GCT XGA GGC GTG-3' in which X was O6mG or an analog in
      which X was paired with C. The reactions in 50 mM Tris-HCl and 1 mM EDTA, pH7.6
      and 37 degrees C, were followed by anion-exchange HPLC in 10 mM NaOH with a NaCl
      gradient. All detected reactions were demethylations of the oligodeoxynucleotides
      except for O6m3DG, which reacted in an unknown manner.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7727388
TI  - The disulfide linkages and glycosylation sites of the human natriuretic peptide
      receptor-C homodimer.
AB  - The natriuretic peptide receptor-C (NPR-C) constitutes greater than 95% of the
      natriuretic peptide binding sites in vivo. This cell surface glycoprotein is a
      disulfide-linked homodimer with a subunit molecular weight of 68,000. Two sources
      and types of ANP affinity-purified human NPR-C were used to map disulfide
      linkages and glycosylation sites of this receptor by mass spectrometry: the
      extracellular domain obtained by papain cleavage of a receptor-IgG fusion protein
      expressed in Chinese hamster ovary cells, and a baculovirus/Sf9-expressed
      cytoplasmic truncation mutant in which 34 of 37 cytoplasmic domain amino acids
      were deleted. Two intramolecular disulfide bonded loops were found in the 435
      amino acid extracellular domain (C63-C91, C168-C216). The juxtamembrane residues
      C428 and C431 are involved in homodimer formation, confirmed by site-directed
      mutagenesis of full-length NPR. Three of the four potential Asn-linked
      glycosylation sites are occupied: N41 (complex), N248 (high mannose), and N349
      (complex; partial occupancy). These data describe the intra- and intermolecular
      linkages in NPR-C, providing a model for the homologous guanylyl cyclase
      receptors, NPR-A and NPR-B; both of the cyclase receptors likely contain the
      first amino-terminal 29 amino acid loop, but only NPR-A possesses the second 49
      amino acid loop in common with NPR-C.

PMID- 7727389
TI  - Regulation of in vitro nucleic acid strand annealing activity of heterogeneous
      nuclear ribonucleoprotein protein A1 by reversible phosphorylation.
AB  - Phosphorylation in vivo of several proteins in the mammalian heterogeneous
      nuclear ribonucleoprotein complex (hnRNP), including A1, has been observed and
      proposed as a regulatory step in pre-mRNA splicing [Maryland, S. H., Dwen, P., &
      Pederson, T. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7764-7768]. We examined the
      ability of recombinant hnRNP protein A1 to act as a substrate for a number of
      purified Ser/Thr protein kinases in vitro. A survey of seven protein kinases
      showed that A1 was heavily phosphorylated by protein kinase C (PKC) and also was
      phosphorylated by casein kinase II, protamine kinase, and protein kinase A. In
      contrast, autophosphorylation-activated protein kinase and two forms of myelin
      basic protein kinase failed to phosphorylate A1. Proteolysis with trypsin and V8
      protease revealed that PKC phosphorylates A1 at three main sites, two in the N
      terminal domain (spanning residues 2-196) and one in the C-terminal domain
      (spanning residues 197-320). Amino acid sequencing revealed that these sites were
      Ser95, Ser192, and Ser199; phosphorylation at Ser192 was more abundant than at
      Ser95 and Ser199. Phosphorylation by PKC inhibited the strand annealing activity
      of A1. Protein phosphatase 2A, but not protein phosphatase 1, dephosphorylated A1
      and reversed the inhibitory effect of PKC phosphorylation on the strand annealing
      activity. A conformational change in the C-terminal domain of A1 was observed
      upon PKC phosphorylation, and this was associated with a decrease in A1's
      affinity for single-stranded polynucleotides. The results are consistent with a
      role of phosphorylation of A1 in regulating its strand annealing activity in
      vivo.

PMID- 7727390
TI  - A site-specific endonuclease derived from a mutant Trp repressor with altered DNA
      binding specificity.
AB  - Site-directed mutagenesis was used to construct mutant Trp repressors with each
      of the 38 possible single amino acid changes of the first 2 amino acid residues
      (Ile79 and Ala80) in the second "recognition" alpha-helix of the helix-turn-helix
      DNA-binding motif. Eight of these mutant repressors with Ile79 and Ala80 changes
      are more active than the wild-type protein when tryptophan is limiting, and are
      super-aporepressors. Eleven mutant repressors have extended DNA-binding
      specificies in vivo, and bind operators which the wild-type repressor cannot. One
      mutant repressor, Lys79, has a classical altered specificity phenotype in vivo,
      and binds the wild-type trp operator less well than wild-type repressor, yet
      binds a mutant operator better than wild-type repressor. A site-specific nuclease
      was derived from Lys79 repressor by constructing a double-mutant protein with
      Lys79 and a sole cysteine residue, Cys49, and alkylating this cysteine with a
      1,10-phenanthroline-copper adduct. This nuclease has an altered specificity of
      DNA binding in vitro. When activated by the addition of thiol and hydrogen
      peroxide, the Lys79 nuclease cleaves operator DNA within its new recognition
      sequence with high efficiency.

PMID- 7727391
TI  - Nested cooperativity in the ATPase activity of the oligomeric chaperonin GroEL.
AB  - Initial rates of ATP hydrolysis by wild-type GroEL were measured as a function of
      ATP concentration from 0 to 0.8 mM. Two allosteric transitions are observed: one
      at relatively low ATP concentrations (< or = 100 microM) and the second at higher
      concentrations of ATP with respective midpoints of about 16 and 160 microM. Two
      allosteric transitions were previously observed also in the case of the Arg-196-
      >Ala GroEL mutant [Yifrach, O., & Horovitz, A. (1994) J. Mol. Biol. 243, 397
      401]. On the basis of these observations a mathematical model for nested
      cooperativity in ATP hydrolysis by GroEL is developed in which there are two
      levels of allostery: one within each ring and the second between rings. In the
      first level, each hepatameric ring is in equilibrium between the T and R states,
      in accordance with the Monod-Wyman-Changeux (MWC) model of cooperativity [Monod
      et al. (1965) J. Mol. Biol. 12, 88-118]. A second level of allostery is between
      the rings of the GroEL particle which undergoes sequential Koshland-Nemethy
      Filmer (KNF)-type transitions from the TT state via the TR state to the RR state
      [Koshland et al. (1966) Biochemistry 5, 365-385]. Using our model, we estimate
      the values of the Hill coefficient for the negative cooperativity between rings
      in wild-type GroEL and the Arg-196-->Ala mutant to be 0.003 (+/- 0.001) and 0.07
      (+/- 0.02), respectively. The inter-ring coupling free energies in wild-type
      GroEL and the Arg-196-->Ala mutant are -7.5 (+/- 0.4) and -3.9 (+/- 0.3) kcal mol
      1, respectively.

PMID- 7727392
TI  - Thermodynamic analysis of the structural stability of the tetrameric
      oligomerization domain of p53 tumor suppressor.
AB  - The structural stability of an amino acid fragment containing the oligomerization
      domain (residues 303-366) of the tumor suppressor p53 has been studied using high
      precision differential scanning calorimetry (DSC) and circular dichroism
      spectroscopy (CD). Previous NMR solution structural determinations have revealed
      that the fragment forms a symmetric 29.8 kDa tetramer composed of a dimer of
      dimers (p53tet) [Lee, W., Harvey, T. S., Yin, Y., Yau, P., Litchfield, D., &
      Arrowsmith, C. H. (1994) Nature Struct. Biol. 1, 877-890]. Thermal unfolding of
      the tetramer is reversible and can be described as a two-state transition in
      which the folded tetramer is converted directly to unfolded monomers (N4<==>4U).
      According to the DSC and CD data, the population of intermediate species
      consisting of folded monomers or dimers is insignificant, indicating that
      isolated dimeric or monomeric structures have a much lower stability than the
      dimer and do not become populated during thermal denaturation under the
      conditions studied. The transition temperature of unfolding is found to be highly
      dependent on protein concentration and to follow the expected behavior for a
      tetramer that dissociates upon unfolding. Experiments conducted at pH 4.0 in 25
      mM sodium acetate at a tetramer concentration of 145.8 microM have a transition
      temperature (Tm) of 75.3 degrees C while at 0.5 microM the value drops to 39.2
      degrees C. The enthalpy change of unfolding at 60 degrees C is 26 kcal (mol of
      monomer)-1 with a heat capacity change of 387 cal (K.mol of monomer)-1. The
      stability of p53tet is dependent on pH and salt concentration.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7727393
TI  - Three-dimensional structure, catalytic properties, and evolution of a sigma class
      glutathione transferase from squid, a progenitor of the lens S-crystallins of
      cephalopods.
AB  - The glutathione transferase from squid digestive gland is unique in its very high
      catalytic activity toward 1-chloro-2,4-dinitrobenzene and in its ancestral
      relationship to the genes encoding the S-crystallins of the lens of cephalopod
      eye. The three-dimensional structure of this glutathione transferase in complex
      with the product 1-(S-glutathionyl)-2,4-dinitrobenzene (GSDNB) has been solved by
      multiple isomorphous replacement techniques at a resolution of 2.4 A. Like the
      cytosolic enzymes from vertebrates, the squid protein is a dimer. The structure
      is similar in overall topology to the vertebrate enzymes but has a dimer
      interface that is unique when compared to all of the vertebrate and invertebrate
      structures thus far reported. The active site of the enzyme is very open, a fact
      that appears to correlate with the high turnover number (800 s-1 at pH 6.5)
      toward 1-chloro-2,4-dinitrobenzene. Both kcat and kcat/KmCDNB exhibit pH
      dependencies consistent with a pKa for the thiol of enzyme-bound GSH of 6.3. The
      enzyme is not very efficient at catalyzing the addition of GSH to enones and
      epoxides. This particular characteristic appears to be due to the lack of an
      electrophilic residue at position 106, which is often found in other GSH
      transferases. The F106Y mutant enzyme is much improved in catalyzing these
      reactions. Comparisons of the primary structure, gene structure, and three
      dimensional structure with class alpha, mu, and pi enzymes support placing the
      squid protein in a separate enzyme class, sigma. The unique dimer interface
      suggests that the class sigma enzyme diverged from the ancestral precursor prior
      to the divergence of the precursor gene for the alpha, mu, and pi classes.

PMID- 7727394
TI  - New sodium channel-blocking conotoxins also affect calcium currents in Lymnaea
      neurons.
AB  - Two new conotoxins that affect both sodium and calcium currents have been
      characterized from the venom of Conus marmoreus, using direct assays on voltage
      gated currents in caudodorsal neurons (CDC) of the freshwater snail Lymnaea
      stagnalis. The designations and amino acid sequences of the new toxins are MrVIA,
      ACRKKWEYCIVPIIGFIYCCPGLICGPFVCV, and MrVIB, ACSKKWEYCIVPILGFVYCCPGLICGPFVCV. Both
      toxins block voltage dependent sodium currents in snail neurons with ED50's of
      0.1-0.2 microM. Effects are also observed on the fast-inactivating calcium
      current subtype in the CDC at > or = 1 microM. At concentrations of 1-5 microM,
      MrVIA acts as a calcium current agonist whereas MrVIB acts as a blocker. At
      higher doses both toxins block the fast-inactivating calcium current. Almost no
      effects of MrVIB are seen on the second (sustained kinetics) CDC calcium current
      subtype, while MrVIA also slightly blocks the sustained current. The calcium
      current block is rapidly reversible, whereas in contrast recovery of the sodium
      current requires extensive wash. MrVIA/B have the same cysteine framework as the
      omega- and delta-conotoxins and a high content of hydrophobic residues, in common
      with the delta-conotoxins. There is only one localized concentration of charged
      residues in MrVIA/B, in the first intercysteine loop. These two conotoxins
      provide unique probes for structure and function studies on voltage-gated sodium
      and L-type calcium channels. Their unusual cross-channel activity suggests they
      may represent an "intermediate" variant of conotoxin, in the diversification of
      one conotoxin structural family that selectively targets either sodium or calcium
      channels.

PMID- 7727395
TI  - Reactivity of carbon monoxide dehydrogenase from Rhodospirillum rubrum with
      carbon dioxide, carbonyl sulfide, and carbon disulfide.
AB  - The reactivities of CO2 and the related compounds COS and CS2 with the nickel-
      and iron- sulfur-containing carbon monoxide dehydrogenase (CODH) from
      Rhodospirillum rubrum have been investigated. Both CO2 and COS were substrates
      for CODH in a reductant-dependent reaction resulting in the formation of CO. CO2
      was reduced to CO and H2O, while COS was reduced to CO and H2S. CO was a potent
      inhibitor of CO2 reduction at dissolved concentrations as low as 1 microM, but
      this inhibition could be prevented by quantitatively trapping CO as it was formed
      by including reduced hemoglobin in the assays. The addition of hemoglobin to the
      assays also allowed the formation of CO to be monitored in real time by following
      the decrease in absorbance at 433 nm resulting from carboxyhemoglobin formation.
      A variety of low-potential reductants, including dithionite, titanium(III)
      citrate, and dithionite-reduced viologens (methyl and benzyl), were suitable
      electron donors for the reduction of CO2 and COS. Dithionite-reduced methyl
      viologen supported the highest rates of CO2 and COS reduction, and the
      stimulation of CO2 reduction (170-fold increased rate over dithionite alone) was
      much more dramatic than the stimulation of COS reduction (2.6-fold increased rate
      over dithionite alone). CO2 was reduced to CO with a Km for CO2 of 190 microM and
      a Vmax of 44 mumol of CO formed min-1 (mg of protein)-1, while COS was reduced
      with a Km for COS of 2.2 microM and a Vmax of 0.51 mumol of CO formed min-1 (mg
      of protein)-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727396
TI  - Carbonyl sulfide and carbon dioxide as new substrates, and carbon disulfide as a
      new inhibitor, of nitrogenase.
AB  - Nitrogenase is the metalloenzyme responsible for the biological reduction of N2
      to NH3. Nitrogenase has been shown to reduce a variety of substrates in addition
      to N2 and protons. General properties of alternative substrates for nitrogenase
      are the presence of N-N, N-O, N-C, and C-C triple or double bonds. In the present
      work, we demonstrate that Azotobacter vinelandii nitrogenase can reduce both C-S
      and C-O bonds. Nitrogenase was found to reduce carbonyl sulfide (COS), to CO and
      H2S at a maximum rate of 37.2 +/- 2.0 nmol min-1 (mg of protein)-1 with a Km of
      3.1 +/- 0.6 mM. The formation of CO from nitrogenase reduction of COS was
      monitored spectrophotometrically in real time by following the formation of
      carboxyhemoglobin. In this assay, the change in the visible absorption spectrum
      of reduced hemoglobin upon binding CO provided a sensitive way to quantify CO
      formation and to remove CO, which is a potent inhibitor of nitrogenase, from
      solution. COS reduction by nitrogenase required the molybdenum-iron protein
      (MoFeP), the iron protein (FeP), and MgATP. The reduction reaction was inhibited
      by MgADP, acetylene, and N2, while H2 was not an inhibitor of COS reduction. The
      pH optimum for COS reduction was 6.5. Nitrogenase was also found to reduce carbon
      dioxide (CO2) to CO and H2O. CO2 was reduced at a maximum rate of 0.8 +/- 0.07
      nmole min-1 (mg of protein)-1 with a calculated Km for CO2 of 23.3 +/- 3.7
      mM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727397
TI  - Steady-state kinetic mechanism of Escherichia coli UDP-N
      acetylenolpyruvylglucosamine reductase.
AB  - The Escherichia coli MurB gene encoding UDP-N-acetylenolpyruvylglucosamine
      reductase was expressed to a level of approximately 100 mg/L as a fusion
      construct with maltose binding protein. Rapid affinity purification, proteolysis,
      and anion exchange chromatography yielded homogeneous enzyme containing 1 mol/mol
      bound FAD. Enzyme was maximally activated by K+, NH4+, and Rb+ at cation
      concentrations between 10 and 50 mM. Steady-state enzyme kinetics at pH 8.0 and
      37 degrees C revealed weak and strong substrate inhibition by NADPH and UDP-N
      acetylenolpyruvylglucosamine, respectively, where the KiS were 910 microM and 73
      microM. Substrate inhibition was pH dependent for both substrates. Initial
      velocity measurements as a function of both substrates produced patterns
      consistent with a ping pong bi bi double competitive substrate inhibition
      mechanism. Data at pH 8.0 yielded kinetic constants corresponding to Km,UNAGEP =
      24 +/- 3 microM, Ki,UNAGEP = 73 +/- 19 microM, Km,NADPH = 17 +/- 3 microM,
      Ki,NADPH = 910 +/- 670 microM, and kcat = 62 +/- 3 s-1. A slow anaerobic exchange
      reaction with thio-NADP+ provided evidence for release of NADP+ in the absence of
      UNAGEP. Alternate reduced nicotinamide dinucleotides, including NHXDPH, 3'-NADPH,
      and alpha-NADPH, were substrates, whereas NADH was not. Several nucleotides,
      including ADP and UDP, were weak inhibitors of the enzyme with inhibition
      constants between 5 and 97 mM. Various analogs of NADP+, including 3'-NADP+, thio
      NADP+, APADP+, NEthDP+, and NHXDP+, were inhibitors of the enzyme with respect to
      NADPH and yielded inhibition constants in the range of 110-1100 microM. Analogs
      without the 2'- or 3'-phosphate of NADPH or NADP+ were not substrates or
      inhibitors. Double inhibition experiments with varied APADP+ and UNAG produced
      inhibition patterns consistent with mutually exclusive inhibitor binding. The
      data suggest that NADPH and UNAGEP share a subsite that prevents both molecules
      from binding at once.

PMID- 7727398
TI  - Inhibitors of CoA-independent transacylase block the movement of arachidonate
      into 1-ether-linked phospholipids of human neutrophils.
AB  - The enzyme CoA-independent transacylase (CoA-IT) has been proposed to mediate the
      movement of arachidonate between phospholipid subclasses and influence the
      formation of arachidonic acid metabolites and platelet-activating factor. To
      substantiate the critical role of CoA-IT, we have developed two structurally
      diverse inhibitors of CoA-IT activity, SK&F 98625 [diethyl 7-(3,4,5-triphenyl-2
      oxo-2,3-dihydro-imidazole-1-yl)heptane phosphonate] and SK&F 45905 [2-[2-(3-4
      chloro-3-(trifluoromethyl)phenyl)-ureido]-4- (trifluoromethyl)phenoxy]-4,5
      dichlorobenzenesulfonic acid]. These compounds were tested for their capacity to
      block microsomal CoA-IT activity using two assay systems, the transacylation of 1
      alkyl-2-lyso-sn-glycero-3-phosphocholine (GPC) and the transfer of
      [14C]arachidonate from 1-acyl-2-[14C]arachidonoyl-GPC to lyso-PE. Both SK&F 98625
      and SK&F 45905 inhibited CoA-IT activity (IC50s 6-19 microM) in these two assays.
      In contrast, SK&F 98625 or SK&F 45905 had little or no effect on other lipid
      modifying activities, including CoA-dependent acyltransferase or
      acetyltransferase. Kinetic analysis revealed that both SK&F 98625 and SK&F 45905
      interact directly with the enzyme and prevented the acylation of
      lysophospholipids in a competitive manner. In intact human neutrophils, both SK&F
      98625 and SK&F 45905 completely blocked the movement of [3H]arachidonate from 1
      acyl-linked phospholipids into 1-alkyl-2-arachidonoyl-GPC and 1-alk-1'-enyl-2
      arachidonoyl-GPE. In contrast, these compounds did not inhibit the incorporation
      of free arachidonic acid into cellular lipids indicating that they did not alter
      CoA-dependent acyl transferase activities in the intact cell.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7727399
TI  - Inhibition of ribonucleotide reductase by nitric oxide derived from thionitrites:
      reversible modifications of both subunits.
AB  - Thionitrites are spontaneous nitric oxide (NO) donors in neutral aqueous
      solutions. Consequently, they inhibit ribonucleotide reductase, the rate-limiting
      enzyme in DNA synthesis, from Escherichia coli and murine adenocarcinoma TA3
      cells. They also inhibit tumor cell proliferation. Reaction of thionitrites with
      protein R1, the large subunit, results in the nitrosation of cysteines, as shown
      from the formation of a chromophore with a characteristic absorption at 340 nm.
      EPR spectroscopy both on whole murine R2-overexpressing L1210 cells and on the
      pure protein showed that the tyrosyl radical of protein R2, the small subunit,
      reversibly couples to the NO radical, presumably leading to nitrosotyrosine
      adducts. Both molecular events might be at the origin of the inhibition of
      ribonucleotide reductase by NO, since a number of cysteines and the tyrosyl
      radical are essential for catalysis. These results identify NO donors as a new
      class of inhibitors of ribonucleotide reductase with potential applications as
      anticancer or antiviral chemotherapy agents.

PMID- 7727400
TI  - Indoleglycerol phosphate synthase-phosphoribosyl anthranilate isomerase:
      comparison of the bifunctional enzyme from Escherichia coli with engineered
      monofunctional domains.
AB  - Putative domain--domain interactions of the monomeric bifunctional enzyme
      indoleglycerol phosphate synthase:phosphoribosyl anthranilate isomerase from
      Escherichia coli were probed by separating the domains on the gene level and
      expressing them as monofunctional proteins. The engineered monofunctional enzymes
      were found to be stable, monomeric proteins with virtually full catalytic
      activity. In addition, binding of indolyglycerol phosphate to the active site of
      indoleglycerol phosphate synthase and binding of reduced 1-[(2
      carboxyphenyl)amino]-1-deoxyribulose 5-phosphate, a competitive inhibitor of both
      indoleglycerol phosphate synthase and phosphoribosyl anthranilate isomerase, were
      almost identical in both the mono- and bifunctional enzymes. Furthermore, no
      association between the monofunctional enzymes was found, neither in vitro, by
      sedimentation and gel filtration experiments, nor in vivo, by coexpression of the
      domains in the same cell. Thus, no selective advantages of the bifunctional
      enzyme from Escherichia coli over the respective monofunctional enzymes were
      found on a functional level. However, the phosphoribosyl anthranilate isomerase
      domain appears to stabilize the indoleglycerol phosphate synthase domain of the
      bifunctional enzyme from Escherichia coli by interactions that seem to subtly
      influence the kinetics of ligand binding.

PMID- 7727401
TI  - Phosphoribosyl anthranilate isomerase catalyzes a reversible amadori reaction.
AB  - Data from steady state and transient kinetics show that the functional
      phosphoribosyl anthranilate isomerase domain of the naturally bifunctional enzyme
      from Escherichia coli has properties similar to those of its artificially excised
      domain. The naturally monofunctional enzyme from Saccharomyces cerevisiae has
      significantly higher values of both kcat and kcat/KMPRA. The primary product of a
      single turnover of phosphoribosylanthranilate is fluorescent, but it slowly
      isomerizes to the nonfluorescent stable product. The latter is the competent
      substrate of indoleglycerol phosphate synthase, which catalyzes the subsequent
      step of tryptophan biosynthesis. The isomerization is characterized by a
      monoexponential decay independent of phosphoribosyl anthranilate isomerase. Due
      to a tentative assignment of the fluorescent, primary product and the
      nonfluorescent, stable product to an enol and a keto compound, respectively,
      tryptophan biosynthesis appears to be rate-limited by an uncatalyzed enol/keto
      tautomerization. A formal kinetic mechanism of the reaction catalyzed by
      phosphoribosyl anthranilate isomerase is proposed that is consistent with the
      combined enzymic and ligand binding properties of the three variants of
      phosphoribosyl anthranilate isomerase.

PMID- 7727402
TI  - Raman spectroscopy of the filamentous virus Ff (fd, fl, M13): structural
      interpretation for coat protein aromatics.
AB  - Site-specific isotope substitutions in the coat protein (pVIII) of the
      filamentous bacterial virus Ff (fd, fl, M13) have been employed to advance
      vibrational band assignments and facilitate structural interpretation of the
      Raman spectrum. We report spectra of phage fd assembled in vivo from pVIII
      subunits incorporating either deuteriophenylalanine (Fd5), deuteriotryptophan
      (Wd5), or deuteriotyrosine (Yd4) residues with labeled ring sites. The deuterated
      aromatics were introduced into fd individually and in combination. On the basis
      of observed isotope shifts, definitive assignments have been developed for all
      prominent Raman bands diagnostic of the pVIII aromatic residues (F11, F42, F45,
      W26, Y21, Y24). The present study constitutes the first direct experimental
      determination of Raman fingerprints of tyrosine and phenylalanine side chains
      within hydrophobic alpha-helical domains and yields unexpected results.
      Importantly, neither Y21 nor Y24 of pVIII exhibits the "canonical" Fermi doublet
      expected in the 820-860 cm-1 interval of the Raman spectrum. Instead, each
      tyrosine exhibits a single band near 853 cm-1. Since the application of
      denaturing conditions is sufficient to generate in fd an apparent Fermi doublet,
      it is concluded that the anomalous singlet is intrinsic to tyrosine environments
      in the native virion assembly. In addition, the Raman results clearly demonstrate
      an interdependence of the environments of aromatic side chains in virion
      subunits. We show that the results on fd isotopomers are also confirmed by Raman
      spectroscopy of Ff virions incorporating the tyrosine mutations Y21M, Y24M, and
      Y21F/Y24S. The Raman marker bands identified for pVIII aromatics modify and
      extend Raman correlations proposed previously for proteins. The unusual
      environments detected for aromatic residues in the mature Ff assembly are
      discussed in relation to recently proposed models for filamentous virion
      architecture.

PMID- 7727403
TI  - Nucleotide-free actin: stabilization by sucrose and nucleotide binding kinetics.
AB  - We prepared nucleotide-free actin in buffer containing 48% (w/v) sucrose. Sucrose
      inhibits the irreversible denaturation of actin that follows nucleotide
      dissociation [Kasai et al. (1965) Biochim. Biophys. Acta 94, 494-503]. Our
      conditions removed nucleotide from approximately 80% of the actin. Stabilization
      of nucleotide-free actin depends on the sucrose concentration. The CD ellipticity
      (x 10(3) deg cm2 dmol-1) at 222 nm of nucleotide-free actin in 48% sucrose is 
      3.54. The ellipticity of denatured nucleotide-free actin in dilute buffer is 
      2.01 and that of native actin is -4.19. In 48% sucrose nucleotide-free actin has
      1.12 and native actin has 0.5 solvent-exposed thiol residues. The conformation of
      native actin is recovered when ATP and Mg2+ are added. Our ability to generate
      stable nucleotide-free actin permitted us to study the kinetics of nucleotide
      binding to actin. The observed rate constant of the reaction is linearly
      dependent on the concentration of epsilon ATP, a fluorescent analog of ATP. The
      inverse of the association rate constant is proportional to the viscosity of the
      solvent with an intercept near the origin as expected for a diffusion-limited
      reaction. The second-order association rate constant for Mg(2+)-ATP and Ca(2+)
      ATP binding to nucleotide-free actin in water at 22 degrees C is 5 x 10(6) M-1 s
      1. The Smoluchowski collision rate constant for actin and ATP is calculated to be
      6.5 x 10(9) M-1 s-1, which makes the "orientation factor" 7.7 x 10(-4). From the
      ratio of the dissociation and association rate constants, we calculate
      dissociation equilibrium constants of 1.2 x 10(-9) M for Mg(2+)-ATP-actin, 4.4 x
      10(-9) M for Mg(2+)-epsilon ATP-actin, and 1.2 x 10(-10) M for Ca(2+)-ATP-actin.

PMID- 7727404
TI  - Role of the C-terminal tail of the GLUT1 glucose transporter in its expression
      and function in Xenopus laevis oocytes.
AB  - Structural determinants for the glucose transport kinetics of the erythrocyte
      glucose transporter have not been established. In this work the role of the
      cytosolic carboxy-terminal tail in the expression and function of the human GLUT1
      isoform in Xenopus oocytes was investigated. Oocyte plasma membrane expression of
      GLUT1 was a saturable function of the amount of mRNA injected. Transport activity
      increased as a linear function of the amount of immunoreactive transporter in the
      plasma membrane. Transport kinetics of human GLUT1 expressed in oocytes resembled
      those of human erythrocyte GLUT1. Addition of up to 31 extra amino acids to the
      carboxy-terminal tail of GLUT1 was without effect on its function in oocytes.
      Removal of the carboxy-terminal 21 amino acids also did not affect GLUT1
      expression or transport kinetics in oocytes. Removal of the entire carboxy
      terminal tail to Phe-450 resulted in a transporter that had moderately decreased
      plasma membrane expression compared to that of GLUT1. However, transport activity
      of this construct was less than 5% of that of GLUT1, and was associated with loss
      of its outward-facing inhibitor binding site. When the carboxy-terminal 29 amino
      acids of GLUT1 were replaced with the corresponding region of GLUT4, transporter
      expression in the plasma membrane and the transport Vmax fell to low levels,
      similar to those of native GLUT4. When the carboxy-terminal 29 or 73 amino acids
      of GLUT1 were swapped into the corresponding region of GLUT4, the transport Vmax
      markedly increased to about one-third to one-half that of GLUT1, although the
      affinity for substrate was halved. These results show that the carboxy-terminal
      tail of the GLUT1 is not critical for targeting of the protein to the plasma
      membrane, but that this region is an important determinant of transport function.

PMID- 7727405
TI  - Transport of adenosine triphosphate into endoplasmic reticulum proteoliposomes.
AB  - We have reconstituted a partially purified extract from rat liver endoplasmic
      reticulum membrane proteins into phosphatidylcholine liposomes. The resulting
      proteoliposomes, of an average diameter of 58 nm, transport intact ATP into their
      lumen in a temperature-dependent manner; transport was saturable (apparent Km =
      0.72 microM) and highly specific: CMP-sialic acid and GTP were transported very
      slowly or not at all. Transport of ATP was inhibited by DIDS (4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid) but not by carboxyatractyloside.
      Previously, we showed that vesicles derived from rat liver and dog pancreas
      endoplasmic reticulum translocate ATP into their lumen in vitro but in these
      studies, following incubations with ATP, most of the phosphate was transferred to
      proteins because of the many kinases, endogenous acceptors for phosphorylation,
      and ATP binding proteins present in the vesicle membranes and lumen. This
      reconstituted system, which yielded a highly functional ATP transporter, can be
      used for further characterization and purification of this and probably other
      nucleotide transporters of the endoplasmic reticulum membrane. Previously used
      reconstitution protocols which were successful for Golgi membrane nucleotide
      transporters did not yield a functional endoplasmic reticulum ATP transporter.

PMID- 7727406
TI  - Structural determinants of the ligand-binding site of the human retinoic acid
      receptor alpha.
AB  - The ligand-dependent transactivating properties of retinoic acid receptors are
      controlled through a complex structure at the C-terminus of these proteins,
      commonly referred to as the hormone binding domain. This domain is involved not
      only in ligand recognition but also in protein-protein interactions such as homo-
      and heterodimerization processes. To identify more precisely regions of the human
      all-trans-retinoic acid receptor alpha (hRAR alpha) that are involved in ligand
      binding, we constructed a series of deletion mutants of this molecule and
      overexpressed them in bacteria. We found that the C-terminal part of the D domain
      (amino acids 186-198) was necessary for ligand binding. The F domain and the 10 C
      terminal amino acids of the E domain were dispensable for high-affinity binding
      of various natural and synthetic retinoids. A further deletion to position 403
      resulted in a moderate decrease in affinity for all-trans-(ATRA) and 9-cis
      retinoic acids, whereas the binding of two RAR alpha-specific ligands (Am80 and
      Am580) was abolished. In addition, hRAR alpha and the minimal hormone binding
      domain (amino acids 186-410) bound ATRA with a positive, cooperative mechanism.
      This behavior was not observed with CD367, a conformationally restricted
      synthetic retinoid. The positive cooperativity could be correlated with stable
      ATRA binding to RAR homodimers, whose formation was triggered by ligand. In the
      same conditions, only monomeric CD367-RAR alpha complexes were detected. These
      data indicate that ligand binding to hRAR alpha requires the presence of part of
      the D domain, whereas the C-terminal end of the E domain is involved in more
      subtle ligand recognition processes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727407
TI  - Enzymatic characterization of immunopurified prohormone convertase 2: potent
      inhibition by a 7B2 peptide fragment.
AB  - Prohormone convertase (PCs) are thought to mediate the controlled proteolysis of
      prohormones and neuropeptide precursors. While recombinant PC1 and furin are
      currently available, thus far it has not been possible to produce recombinant
      PC2. We have used conditioned medium obtained from the mouse insulinoma cell line
      beta TC3 to generate a working preparation of enzymatically active PC2 through
      immunopurification. Immunopurified PC2 cleaved the fluorogenic substrate Cbz-Arg
      Ser-Lys-Arg-AMC in a time- and calcium-dependent manner. It was half-maximally
      stimulated at 75 microM Ca2+, had an optimum pH of 5, and exhibited PCMS and EDTA
      sensitivity similar to that reported for furin and PC1. The tight-binding
      inhibitor 27 kDa 7B2 was used to calculate the Kd for this inhibitor and the
      active enzyme concentration. The Kd was 7.3 +/- 1.7 nM, and the turnover rate of
      PC2 was 5.2 molecules substrate per enzyme molecule per minute. The specific
      activity was 4.9 nmol/micrograms/h (assuming a molecular mass for PC2 of 64 kDa).
      The enzyme preparation was able to cleave recombinant proenkephalin at at least
      four of the expected paired basic sites in the absence, but not in the presence,
      of 27 kDa 7B2. Since 21 kDa 7B2 is functionally inactive as a proteinase
      inhibitor, we examined the inhibitory activity of the carboxy-terminal portion of
      27 kDa 7B2 (7B2 CT-peptide). Synthetic peptides were used to demonstrate that the
      7B2 CT-peptide (a) represents a potent inhibitor of PC2 (Ki = 57 nM), (b) can
      block the conversion of proPC2 to PC2, and (c) can block the PC2-mediated
      conversion of proenkephalin to smaller peptide fragments.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7727408
TI  - Blockade by botulinum neurotoxin B of catecholamine release from adrenochromaffin
      cells correlates with its cleavage of synaptobrevin and a homologue present on
      the granules.
AB  - Botulinum neurotoxin type B blocks transmitter release via a selective
      endoproteolysis of the small clear vesicle membrane protein synaptobrevin that is
      essential for neuro-exocytosis. In view of the distinct characteristics of
      exocytosis of adrenochromaffin granules and considering the controversy over the
      presence of synaptobrevin on the latter, this study aimed to determine the
      molecular basis of the inhibition by this toxin of secretion from chromaffin
      cells. Thus, affinity-purified antibodies against a synaptobrevin synthetic
      peptide were used to quantify its concentrations in subcellular fractions of
      bovine adrenal medulla. The latter, as well as density gradient centrifugation
      and size-exclusion chromatography, showed that > 70% of the protein copurifies
      with the granules and their marker, dopamine beta-hydroxylase. Notably, much
      lower concentrations of synaptobrevin and synaptophysin were found in chromaffin
      granules than in synaptic small clear vesicles (approximately 9% and
      approximately 2%, respectively); however, isolated granule membranes exhibited
      greater enrichments (approximately 35% and approximately 9%). A second
      immunoreactive protein was colocalized with synaptobrevin on chromaffin granules;
      in view of its susceptibility to the toxin and lower M(r), it is assumed to be
      cellubrevin and, also, because of its high homology. Involvement of synaptobrevin
      and cellubrevin in Ca(2+)-triggered granule exocytosis was established by the
      demonstrated correlation between the extent of botulinum neurotoxin B-induced
      inhibition of secretion and their selective proteolysis following introduction of
      the toxin into intact chromaffin cells. On the basis of these collective
      findings, it is concluded that these proteins occur on chromaffin granules and
      one or both are essential for exocytosis.

PMID- 7727409
TI  - Resonance Raman studies of catecholate and phenolate complexes of recombinant
      human tyrosine hydroxylase.
AB  - Human tyrosine hydroxylase isoform 1 (hTH1) was expressed in Escherichia coli,
      purified as the apoenzyme, and reconstituted with iron. The resonance Raman
      spectra of hTH1 complexed with dopamine, noradrenaline, tyramine, and catechol
      have been studied and compared to those obtained for TH isolated from bovine
      adrenal glands or rat phaeochromocytoma tissue. A TH-phenolate complex is
      reported for the first time. Using dopamine selectively 18O-labeled in the 3
      position or both 3- and 4-hydroxy positions, we have been able to assign
      unambiguously the origin of the low-frequency vibration bands: the band at 631 cm
      1 involves the oxygen in the 4-position; the band at 592 cm-1 involves the oxygen
      in the 3-position, and the band around 528 cm-1 is shifted by both, suggesting a
      chelated mode vibration. A small shift of the 1275 cm-1 band and no shift of the
      1320 cm-1 band were observed, showing that those two bands involve essentially
      ring vibrations of the catecholate moiety, rather than the C--O stretching
      vibration as previously suggested. The spectrum of the catechol-d6-hTH1 complex
      confirms this assignment. The resonance Raman spectra of the 54Fe, 56Fe, or 57Fe
      isotope-containing enzymes complexed with dopamine are virtually identical,
      showing that the component of the iron in the approximately 600 cm-1 vibrations
      is too small to be observed. These results provide a better understanding of the
      Raman properties of iron-catecholate complexes in this enzyme, as well as in
      other metalloproteins and model compounds.

PMID- 7727410
TI  - Denaturation of cytochrome P450 2B1 by guanidine hydrochloride and urea: evidence
      for a metastable intermediate state of the active site.
AB  - A metastable intermediate was found in the course of the denaturation of purified
      cytochrome P450 2B1 by increasing concentrations of guanidine hydrochloride
      (GuHCl). The metastable intermediate has no or low absorbance at 450 nm in the
      reduced carbon monoxide difference spectrum and has no absorbance at 420 nm. The
      intermediate is easily converted to P420 by increasing concentrations of GuHCl.
      Before it becomes P420, the cytochrome can be completely reconverted to native
      P450 by dilution and incubation at 4 degrees C. Cytochrome P420 resulting from
      exposure to higher concentrations of GuHCl (> 3 M) failed to be reconverted to
      P450 by dilution. Denaturation of P450 2B1 by exposure to low concentrations of
      urea (< 2 M) is also completely reversible but no obvious intermediate is
      detectable. An intermediate is observed, however, when the urea denaturation is
      conducted in the presence of 1 M NaCl. As is the case with higher concentrations
      of GuHCl, cytochrome P450 denatured by exposure to 5 M or higher concentrations
      of urea is not reversible. The failure of reconversion of P420 denatured by
      exposure of cytochrome P450 to high concentrations of GuHCl or urea is probably
      attributable to the extensive unfolding of the apoprotein, which favors
      aggregation, rather than to heme loss. Our results also suggest that the active
      site is more sensitive to denaturants than other regions of the protein.

PMID- 7727411
TI  - A limiting law for the electrostatics of the binding of polypeptides to
      phospholipid bilayers.
AB  - Two cysteine-substituted variants of a peptide derived from the first 25 residues
      of the presequence for subunit IV of cytochrome c oxidase were synthesized and
      modified with a nitroxide spin label. The equilibrium partitioning of these spin
      labeled peptides into negatively charged phospholipid vesicles was studied with
      electron paramagnetic resonance (EPR) to investigate the binding energetics. It
      is found that the binding equilibrium constant is an explicit function of a
      unique variable, the membrane surface potential psi in the Gouy-Chapman-Stern
      theory. Moreover, at low psi (< 0.5RT/F) the binding equilibrium is described by
      the linear dependence of the transfer free energy delta G(el) on psi with a slope
      equal to the full formal charge of the peptides. However, the partition constant
      levels off at higher psi, suggesting departure from the ideal limiting behavior.

PMID- 7727412
TI  - Isolation and spectroscopic characterization of a plantlike photosystem II
      reaction center from the cyanobacterium Synechocystis sp. 6803.
AB  - A chlorophyll-protein complex has been isolated from the cyanobacterium
      Synechocystis sp. PCC 6803 that closely resembles higher plant photosystem II
      reaction centers in spectral properties. The Synechocystis complex has a pigment
      content of 5-7 chlorophyll a molecules:1 Cyt b559:2 pheophytins; an optical
      absorption redmost transition at approximately 675 nm; and a nonconservative
      circular dichroism red signal, with extrema at 682 (+) and 652 (-) nm. Upon
      illumination, the Synechocystis D1/D2/Cyt b559 complex accumulates reduced
      pheophytin. LDS-PAGE and/or immunoblotting showed the D1, D2, and Cyt b559
      proteins, aggregated and degraded forms of D1 and possibly D2, and traces of ATP
      synthase and the CP47 photosystem II chlorophyll protein. The availability of
      such a Synechocystis preparation opens the way for employing site-directed
      mutagenesis in studying primary reactions of oxygenic photosynthesis.

PMID- 7727413
TI  - Infrared-detectable groups sense changes in charge density on the nickel center
      in hydrogenase from Chromatium vinosum.
AB  - Fourier transform infrared studies of nickel hydrogenase from Chromatium vinosum
      reveal the presence of a set of three absorption bands in the 2100-1900 cm-1
      spectral region. These bands, which do not arise from carbon monoxide, have line
      widths and intensities rivaling those of a band arising from the carbon monoxide
      stretching frequency (v(CO)) in the Ni(II).CO species of this enzyme [Bagley, K.
      A., Van Garderen, C. J., Chen, M., Duin, E. C., Albracht, S. P. J., & Woodruff,
      W. H. (1994) Biochemistry 33, 9229-9236]. The positions of each of these three
      infrared absorption bands respond in a consistent way to changes in the formal
      redox state of the nickel center and to the photodissociation of hydrogen bound
      to the nickel. Up to eight different states of the nickel center have been
      produced, depending on the redox state and/or the activity state of the enzyme
      and the presence of carbon monoxide. In seven of these states, the three IR
      absorption bands in the set have unique frequency positions. It is concluded that
      the set is due to intrinsic, non-protein groups in the enzyme, whose identities
      are presently unknown, and that these groups are situated very close to the
      nickel center and sense the charge density at the Ni site.

PMID- 7727414
TI  - Anesthetics reduce the magnitude of the membrane dipole potential. Measurements
      in lipid vesicles using voltage-sensitive spin probes.
AB  - Lipid membranes possess a large internal dipole potential that greatly exceeds
      the magnitude of typical transmembrane or surface potentials. The volatile
      general anesthetics, halothane, isoflurane and enflurane were tested by the use
      of positively and negatively charged hydrophobic ion spin labels in lipid bilayer
      vesicles for their ability to modulate the membrane dipole potential. These
      anesthetics decreased the binding of negatively charged hydrophobic ion spin
      probes based on trinitrophenol, but increased the binding of positively charged
      hydrophobic ion probes based on triphenylalkylphosphoniums. They also enhanced
      the transit rates for both hydrophobic anions and cations; however, translocation
      rates were enhanced to a greater extent for the cation probes compared to the
      anion probes. The changes in binding constant for cations versus anions could be
      accurately accounted for using a simple model for the free energy profile for
      hydrophobic ions across membranes, and indicate that these anesthetics decrease
      the membrane dipole potential. From a fit of the experimental data to this model,
      anesthetics could promote a decrease in the dipole potential in two ways. First,
      anesthetics appear to modify the effective dipole moment in the membrane
      interface and may accomplish this by orienting their molecular dipole
      antiparallel to the intrinsic dipoles at the interface. Second, they modify the
      membrane dielectric constant, leading to a decrease in the field across the
      interface. At equivalent membrane concentrations, isoflurane, enflurane, and
      halothane produced similar changes in the dipole potential and decreased the
      dipole potential as much as 65 mV at a membrane mole fraction of 0.20.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7727415
TI  - Interactions between the amino- and carboxyl-terminal regions of G alpha
      subunits: analysis of mutated G alpha o/G alpha i2 chimeras.
AB  - Receptors activate the G alpha subunits of heterotrimeric G proteins by binding
      to the C-terminus and reducing their affinity for bound GDP, therefore promoting
      exchange of GDP for GTP. Although this general mechanism is the same for all G
      alpha subunits, different G alpha subunits vary in nucleotide binding and
      hydrolysis even though the residues that make up the guanine nucleotide binding
      site are virtually identical. We have shown previously that truncation of 14
      amino acids from the C-terminus of G alpha o decreased the apparent affinity for
      GDP and permitted us to see an activated conformation with GTP [Denker, B. M., et
      al. (1992) J. Biol. Chem. 267, 9998-10002]. To test whether mutations in the
      receptor binding region lead to different phenotypes in closely related G alpha
      subunits, we made the equivalent deletions in G alpha i2, synthesized the
      proteins in vitro in a rabbit reticulocyte lysate and used the pattern of native
      tryptic proteolysis as an index of conformation. The phenotype of truncated G
      alpha i2 was different from that of truncated G alpha o: GDP affinity was
      reduced, but we could not detect an activated conformation with GTP (although GTP
      gamma S activated normally). Analysis of shorter deletions showed that loss of
      three hydrophobic residues (between 11 and 13 residues from the C-terminus) was
      responsible for the phenotypes. To define the regions of G alpha o and G alpha i2
      that were responsible for their different phenotypes, we used a conserved BamHI
      site (codon 212) to make chimeras. Each chimera truncated at the C-terminus had
      the phenotype of the donor of the amino-terminal portion. Both truncated chimeras
      were activated by GTP gamma S-like wild-type proteins, and both had decreased
      apparent affinity for GDP. Full-length chimeric subunits behaved like wild-type
      proteins. The crystal structure of G alpha t and G alpha i1 shows that the three
      hydrophobic amino acids we have identified make contact with residues in the N-
      and C-terminal portions of the protein. Our studies point to the importance of
      the contacts in the N-terminal region (start of beta strands 1 and 3) that may
      stabilize the C-terminal alpha helix, affect nucleotide binding, and determine
      the characteristic features of different G alpha subunits.

PMID- 7727416
TI  - Biosynthetic conversion of phosphatidylglycerol to sn-1:sn-1'
      bis(monoacylglycerol) phosphate in a macrophage-like cell line.
AB  - Bis(monoacylglycerol) phosphate has a unique stereoconfiguration of sn-glycero-1
      phospho-1'-sn-glycerol and is synthesized from exogenous phosphatidylglycerol by
      macrophages. Previous work by our laboratory showed that the macrophage-like cell
      line RAW 264.7 synthesizes sn-glycero-1-phospho-1'-sn-glycerol
      bis(monoacylglycerol) phosphate. Here we describe studies using RAW 264.7 cells
      that examine the biosynthetic pathway by which bis(monoacylglycerol) phosphate is
      formed. Experiments were conducted using precursors that were specifically
      radiolabeled on the glycerol backbone in order to examine the stereoconfiguration
      of the intermediates and products formed in intact RAW 264.7 cells. The results
      of our studies indicate that a complex series of reactions are involved in the
      synthesis of bis(monoacylglycerol) phosphate. In this proposed pathway
      phosphatidylglycerol is hydrolyzed to form 1-acyllysophosphatidylglycerol which
      is then acylated on the headgroup glycerol to form the sn-glycero-1-phospho-1'-sn
      glycerol enantiomer of bis(monoacylglycerol) phosphate. The sn-glycero-1-phospho
      1'-sn-glycerol enantiomer of bis(monoacylglycerol) phosphate is then thought to
      undergo a stereoconversion that proceeds via the required removal of the acyl
      group at the sn-1 position. The resulting sn-glycero-1-phospho-1'-sn-glycerol
      enantiomer of lysophosphatidylglycerol with the acyl moiety on the original
      headgroup glycerol is then acylated to form sn-glycero-1-phospho-1'-sn-glycerol
      bis(monoacylglycerol) phosphate.

PMID- 7727417
TI  - Characterization of the recombinant C-terminal domain of dystrophin:
      phosphorylation by calmodulin-dependent protein kinase II and dephosphorylation
      by type 2B protein phosphatase.
AB  - We report that the C-terminal domain of skeletal muscle dystrophin expressed as a
      fusion protein with glutathione S-transferase (designated GST-CT-1) is a
      substrate for Ca2+/calmodulin-dependent phosphorylation and dephosphorylation.
      GST-CT-1 and GST-CT-1F (GST-CT-1 truncated by 20-25 residues) were phosphorylated
      by Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). The
      stoichiometries of phosphorylation by CaM kinase II were 1.65 mol of Pi/mol of
      GST-CT-1 and 0.39 mol of Pi/mol of GST-CT-1F, respectively, suggesting that the
      principal site(s) of phosphorylation is (are) located in the C-terminal 20-25
      residues that are missing from GST-CT-1F. The GST-CT-1 fusion protein was
      phosphorylated on both serine and threonine residues, whereas GST-CT-1F was
      phosphorylated only on serine. CaM kinase II-phosphorylated GST-CT-1 and GST-CT
      1F were efficiently dephosphorylated by calcineurin, a Ca2+/calmodulin-dependent
      protein phosphatase (type 2B protein phosphatase). Importantly, calcineurin was
      found to be associated with a purified sarcolemmal membrane preparation enriched
      in dystrophin. Type 2A protein phosphatase isolated from smooth muscle (SMP-I)
      and its catalytic subunit (SMP-ic) also dephosphorylated GST-CT-1, but were less
      active toward these substrates than was calcineurin. Type 2C phosphatase (SMP-II)
      and type 1 protein phosphatases [SMP-III, SMP-IV, and myosin-associated
      phosphatase (PP1M) of smooth muscle and skeletal muscle protein phosphatase 1c]
      were ineffective in dephosphorylating the C-terminal region of
      dystrophin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727418
TI  - Enzymatic and metabolic studies on retrograde regulation mutants of yeast.
AB  - Two nuclear genes, RTG1 and RTG2, which sense the functional state of yeast
      mitochondria, have been described recently. Yeast strains with null alleles of
      either of these two genes (delta rtg1, delta rtg2) cannot grow on acetate as the
      sole carbon source and are auxotrophic for glutamate and aspartate. We report
      here a series of metabolic experiments and enzyme activity measurements that were
      made in an attempt to determine the reason for the acetate- phenotype and the
      glutamate/aspartate auxotrophy. Decreases in the activities (approximately 50%)
      in mitochondrial citrate synthase (CS1), acetyl-CoA synthetase, NAD isocitrate
      dehydrogenase, and pyruvate carboxylase were noted. When CS1 was overexpressed in
      the delta rtg1 and delta rtg2 mutants, these strains could grow on acetate but
      were still auxotrophic for glutamate/aspartate. We propose that, in the mutant
      strain, CS1 activity becomes limiting for efficient acetate utilization, but that
      other complex metabolic interactions are affected, limiting production of
      intermediates that would allow synthesis of glutamic and aspartic acids.

PMID- 7727419
TI  - NMR studies of the conformations and location of nucleotides bound to the
      Escherichia coli MutT enzyme.
AB  - The MutT enzyme catalyzes the hydrolysis of nucleoside triphosphates to
      nucleoside monophosphates and pyrophosphate by substitution at the rarely
      attacked beta-phosphorus. Nucleotides containing bulky substituents at the 8
      position of the purine ring are preferentially hydrolyzed. The conformation of
      the MutT-bound nonhydrolyzable substrate analog Mg(2+)-AMPCPP, determined by 10
      intramolecular NOEs and molecular dynamics refinement using a full relaxation
      matrix analysis with back-calculation of the NOESY intensities, is high anti (chi
      = 53 +/- 9 degrees), with a C2'-exo, O1'-endo sugar pucker. Similarly, the
      product of dGTP hydrolysis, dGMP, also binds MutT in a high anti (chi = 73 +/- 9
      degrees) C1'-endo conformation based on seven intramolecular NOEs. Such high anti
      rotations of the base would allow MutT to accommodate nucleotides substituted at
      the C-8 position with no intramolecular clashes. Changes in chemical shifts in
      the 1H-15N spectra of the enzyme induced by Mg2+ and Mg2+ AMPCPP suggest that the
      metal activator and nucleotide interact with residues in loop I, at the carboxyl
      end of helix I, loop II, loop III, and beta-strands A and B of the secondary
      structure of MutT. The displacement of Mg2+ by Mn2+ causes the selective
      disappearance due to paramagnetic broadening of 1H-15N cross peaks from G37, G38,
      and K39 in loop I and E57 in helix I. Eleven intermolecular NOEs between
      Mg2+AMPCPP and hydrophobic residues of MutT are found, three of which are
      tentatively assigned to L67 in loop II and three to L54 in helix I. Similarly,
      seven intermolecular NOEs between dGMP and hydrophobic residues of the enzyme are
      found, four of which are tentatively assigned to L54 and two to V58, both in
      helix I. These interactions indicate that the loop I-helix I-loop II motif
      contributes significantly to the active site of MutT in accord with mutagenesis
      studies and with sequence homologies among MutT-like NTP pyrophosphohydrolases.

PMID- 7727420
TI  - 1H and 15N magnetic resonance assignments, secondary structure, and tertiary fold
      of Escherichia coli DnaJ(1-78).
AB  - We report the 1H and 15N chemical shift assignments along with an NMR-derived
      preliminary structure for DnaJ(1-78), a highly conserved N-terminal domain of
      DnaJ, the Escherichia coli Hsp40 homolog. This 9 kDa domain is believed to
      cooperate with DnaK, the E. coli Hsp70 homolog, in regulating a variety of
      cellular functions. Heteronuclear 3D NMR experiments were carried out on a
      uniformly 15N-labeled DnaJ(1-78), which is a stable, folded fragment. Standard
      15N-edited NMR techniques afforded complete assignment of the backbone amide 1H
      and 15N pairs and partial assignment of the side-chain 1H and 15N atoms. The
      secondary structure of DnaJ(1-78) was determined from NOE connectivities obtained
      from 3D 15N-separated and 2D homonuclear NOESY spectra as well as 3JHNH alpha
      coupling constants obtained from a DQF-COSY spectrum and a 15N-edited HNHA
      experiment. The stability of secondary structural elements was assessed by
      monitoring amide exchange rates, and a model for the three-dimensional fold of
      these elements was derived from a set of long-range contacts extracted from
      homonuclear 2D NOESY experiments. The analysis indicates that DnaJ(1-78) is
      comprised of four alpha-helices and no beta-sheet with a short unstructured loop
      between antiparallel helices II and III. The shorter N-terminal and C-terminal
      helices make contacts with helices II and III at points well removed from the
      central loop. A discussion of how this preliminary structural model may explain
      mutation data from other laboratories is presented.

PMID- 7727421
TI  - Activator carbamino carbon to inhibitor phosphorus internuclear distances in
      ribulose-1,5-bisphosphate carboxylase/oxygenase. A solid-state NMR study.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is a hexadecamer of
      approximately 550 kDa in most organisms. Rotational-echo double-resonance (REDOR)
      and transfer-echo double-resonance (TEDOR) solid-state NMR were used to obtain
      the average internuclear distance between the 99% 13CO2-labeled activator
      carbamino carbon to the phosphate phosphorus nuclei of active-site-bound 2
      carboxy-D-arabinitol 1,5-bisphosphate (CABP), in freeze-quenched, lyophilized
      samples of confrey Rubisco. The distance 7.5 +/- 0.5 A determined by solid-state
      NMR is in agreement with the distance of 7.7 A inferred from the crystal
      structure coordinates for spinach Rubisco-CABP-CO2-Mg2+ quaternary complex.

PMID- 7727422
TI  - Prostaglandin E2 down-regulates the expression of HLA-DR antigen in human colon
      adenocarcinoma cell lines.
AB  - Prostaglandins (PG) have been implicated in the pathogenesis of cancer and play
      an important role in immune regulation. Colon cancer is associated with elevated
      levels of PGE2, while aspirin, the prototypical inhibitor of PG synthesis,
      appears to reduce the incidence of colon cancer by 50%. We have observed that in
      human colon cancer the expression of HLA class I and II antigens is reduced or
      lost; loss of HLA antigens is suspected to be a mechanism by which the malignant
      cell escapes the immune surveillance. We investigated the effect of these
      eicosanoids on the expression of HLA antigens in human colon adenocarcinoma cell
      lines. PGE2 down-regulated the expression of the class II antigen HLA-DR in
      SW1116 cells (65% reduction at 2.8 x 10(-8) M). This effect was dose- and time
      dependent, reversible, and specific (PGF2 alpha and LTB4 had no effect; the
      expression of carcinoembryonic antigen and class I genes were not affected).
      Aspirin induced the expression of HLA-DR in HT29 cells, a cell line not
      expressing constitutively HLA-DR. The reduction of HLA-DR by PGE2 was accompanied
      by reduced messenger RNA (mRNA) levels of HLA-DR alpha and reduced transcription
      of the corresponding gene. In contrast to HLA-DR, none of these three eicosanoids
      affected the expression of HLA class I genes, as assessed via determination of
      protein expression by fluorescence flow cytometric analysis and evaluation of the
      corresponding class I mRNA levels. We conclude that PGE2 specifically down
      regulates the expression of HLA-DR, while it does not affect the expression of
      class I antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727423
TI  - Galactose-1-phosphate uridylyltransferase from Escherichia coli, a zinc and iron
      metalloenzyme.
AB  - Galactose-1-P uridylyltransferase purified from Escherichia coli cells grown in
      enriched medium contains approximately 1.2 mol of tightly bound zinc/mol of
      subunits as well as variable amounts of iron, up to 0.7 mol/mol of subunits, and
      no detectable Ca, Cd, Cu, Mo, Ni, Co, Mn, As, Pb, or Se. The chelators, 1,10
      phenanthroline, 8-hydroxyquinoline, 8-hydroxyquinoline sulfonate, and 2,2'
      bipyridyl remove metal ions from the enzyme and allow the importance of zinc and
      iron to be evaluated. Dialysis of this enzyme against 2 mM 1,10-phenanthroline, 8
      hydroxyquinoline sulfonate, and 2,2'-bipyridyl at millimolar concentrations
      slowly removes both zinc and iron from the enzyme (t1/2 = 4 days at 24 degrees C)
      with concomitant loss of enzymatic activity. In chelation experiments utilizing
      1,10-phenanthroline, residual enzymatic activity was found to be proportional to
      the zinc content, to the iron content, and to the sum of zinc and iron. UDP
      glucose (0.35 mM) protects the enzyme against loss of metal ions and activity in
      the presence of 1,10-phenanthroline, whereas glucose-1-P at 70 mM (400 x Km)
      fails to protect. The enzyme purified from cells grown on a minimal medium
      containing inorganic salts and glucose supplemented with either ZnSO4 or FeSO4
      shows approximately the same level of enzymatic activity as the enzyme from cells
      grown on enriched medium. These experiments showed that enzymatic activity is
      supported by either iron or zinc associated with two sites in the enzyme. Enzyme
      depleted of metal ions by chelators can be partially reactivated by addition of
      ZnSO4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727424
TI  - Role of Tyr-22 in the binding of Pf3 ssDNA binding protein to nucleic acids.
AB  - A Tyr-22-->Phe-22 (Y22F) mutant of the single-strand DNA binding protein (ssDBP)
      of the filamentous phage Pf3 was obtained by site-directed mutagenesis. An
      alignment of protein sequences indicates that Tyr-22 of the Pf3 ssDBP corresponds
      to Tyr-26 of the fd g5p, a tyrosine within the DNA-binding loop. The mutant Y22F
      Pf3 protein had a CD spectrum very similar to that of native, wild-type Pf3 ssDBP
      and could bind to both DNA and RNA polymers. In CD titrations of poly[r(A)],
      poly[r(C)], and Pf3 ssDNA with the Y22F mutant, the saturation endpoints remained
      the same as for titrations performed with wild-type Pf3 ssDBP, indicating that
      the mutant protein retained the same n = 2 mode of binding as the wild-type
      protein. However, a second stoichiometric mode of binding at a ratio of one
      protein monomer to about four nucleotides (n = 4) was observed for titrations of
      these nucleic acids with the Y22F mutant protein. Both proteins showed only an n
      = 2 mode of binding to poly[d(A)], poly[d(C)], and poly[d(T)] and only an n = 3
      mode of binding to poly[r(U)]. Distinctly different CD spectral changes of the
      nucleic acid were observed in titrations of poly[d(A)] with the Y22F mutant and
      the wild-type protein. Therefore, the mutant and wild-type ssDBP interact
      differently with some nucleic acids, depending on the base and sugar composition,
      providing evidence that Tyr-22 is indeed in the DNA-binding loop and may be
      important in the sequence discrimination of the binding of the Pf3 ssDBP.

PMID- 7727425
TI  - Description of an IL-1-responsive kinase that phosphorylates the K protein.
      Enhancement of phosphorylation by selective DNA and RNA motifs.
AB  - The K protein was first identified in the heterogeneous ribonucleoprotein
      particle (hnRNP). Subsequently, K protein was shown to bind sequence-specific
      single-and double-stranded DNA, stimulate transcription, and bind Src, Fyn, Lyn,
      and Vav via SH3 interactions. The K protein also binds to the kappa B enhancer
      motif which stimulates its phosphorylation in vitro by an associated
      serine/threonine kinase. To gain more insight into this unique nucleic acid
      dependent phosphorylation process, we set out to examine the regulation of this
      kinase. We demonstrate that the K protein exists in a complex with an IL-1
      responsive kinase and that phosphorylation of the K protein by this kinase is
      augmented by either cognate DNA or RNA sequences. The IL-1-responsive kinase
      activity associated with the K protein is reduced by phosphatase treatment,
      suggesting that the K protein kinase activity is regulated by phosphorylation.
      The observation that phosphorylation of the K protein is DNA- or RNA-dependent
      and IL-1-responsive suggests that the function of the K protein is tightly
      regulated.

PMID- 7727426
TI  - Folate receptor type gamma is primarily a secretory protein due to lack of an
      efficient signal for glycosylphosphatidylinositol modification: protein
      characterization and cell type specificity.
AB  - A novel isoform of the human folate receptor (FR, type gamma) was recently
      identified in hematopoietic tissues [Shen et al. (1994) Biochemistry 33, 1209
      1215]. In that report, Cos-1 cells, transiently transfected with the cDNA for FR
      gamma, produced relatively poor expression of the receptor on the cell surface.
      In this study, several recombinant Chinese hamster ovary (CHO) cell lines were
      produced by stable transfection with the cDNA for FR-gamma followed by
      amplification. Similar recombinant CHO cell lines were produced that expressed
      the glycosylphosphatidylinositol-(GPI-) anchored FR type beta and a truncated
      form of FR type beta (FR-beta delta), in which the normal carboxyl-terminal
      signal for GPI anchor attachment was deleted. Both FR-gamma-and FR-beta delta
      expressing CHO cells produced a [3H]folic acid binding protein in the medium with
      a similar time course over a 24-h period; in contrast to intact FR-beta,
      relatively insignificant amounts of either FR-gamma or FR-beta delta were
      associated with the CHO cell surface and this was unaltered by the absence of
      serum in the medium. The FR-gamma- and FR-beta delta-producing CHO cells did not
      differ significantly in intracellular FR levels. Furthermore, the mRNA level for
      FR-gamma did not exceed that for FR-beta delta. When deglycosylated with hydrogen
      fluoride, both FR-gamma and FR-beta delta showed similar apparent molecular
      weights on Western blots as predicted for the intact polypeptides.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7727427
TI  - Interactions of lyso 1-palmitoylphosphatidylcholine with phospholipids: a 13C and
      31P NMR study.
AB  - 13C and 31P NMR spectroscopy were used to monitor interactions of lyso 1
      palmitoylphosphatidylcholine (LPPC) in the interfacial region of egg
      phosphatidylcholine (PC) bilayers and determine the effect of LPPC on the
      phospholipid bilayer structure. 13C NMR spectroscopy of small amounts (0.5-10
      mol%) of 13C carbonyl-enriched LPPC cosonicated with egg PC to form small
      unilamellar vesicles (SUVs) revealed separate carbonyl signals for LPPC in the
      inner and outer leaflets of the vesicles. The ratio of LPPC in the outer leaflet
      to that in the inner leaflet was > or = 3/1. Exchange of LPPC between bilayer
      leaflets ("flip-flop") was too slow to be measured (t1/2 > 12 h). Albumin added
      to the external buffer of LPPC/PC vesicles was shown by 13C NMR to extract LPPC
      only from the outer leaflet. LPPC was a poor detergent in egg PC multilayers and
      SUVs. Stable SUVs were prepared by cosonicating egg PC with up to 30 mol% LPPC,
      and preformed SUVs incorporated up to 40 mol % of LPPC (added as an aqueous
      solution) without undergoing any morphological changes as evidenced by 31P NMR
      spectroscopy. The presence of oleic or palmitic acid did not have observable
      effects on properties of LPPC in SUVs, such as the localization of the LPPC
      carbonyl in the interface, and the transbilayer distribution and movement of
      LPPC. The apparent pKa of the fatty acid (FA) carboxyl at the membrane interface
      (7.7) measured by 13C NMR was not affected by LPPC, but the FA carboxyl carbon
      resonance showed linewidth changes near the apparent pKa that were dependent on
      the FA/LPPC ratio. These data suggest weak interactions in the interfacial region
      between FA and LPPC when both lipids are present at low levels in PC vesicles.

PMID- 7727428
TI  - Calorimetric analysis of the binding of lectins with overlapping carbohydrate
      binding ligand specificities.
AB  - The thermodynamics of binding of a system of plant lectins specific for the
      oligosaccharide methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside
      have been studied calorimetrically. This system of lectins consists of
      concanavalin A, the lectin isolated from Dioclea grandiflora, and the lectin from
      Galanthus nivalis. The group thus contains lectins with similar structures and
      similar binding properties as well as lectins with different structures but
      similar binding properties. Concanavalin A and the lectin from Dioclea are highly
      homologous, while the lectin from Galanthus nivalis shares no sequence homology
      with either of the legume lectins, although it also binds the mannose
      trisaccharide tightly. Calorimetric data for oligosaccharide binding to both of
      the legume lectins suggests that the total binding site comprises a single high
      affinity site and an additional extended site. The pattern of binding for the
      lectin from Galanthus is significantly different. Binding studies with the same
      saccharides indicate that the lectin has binding sites designed specifically for
      the 1-->3 and 1-->6 arms of the mannose trisaccharide that are unable to
      accommodate other saccharides. Enthalpy--entropy compensation was observed for
      several saccharides as a function of lectin structure. Contributions of solvation
      effects to the enthalpy of binding and the configurational entropies were
      determined experimentally. For those systems studied here, solute-solute
      attractive interactions and configurational entropies were the greatest
      contributors to enthalpy-entropy compensation. Our studies clearly demonstrate
      that, despite their common affinity for the mannose trisaccharide, the three
      lectins bind oligosaccharides very differently.

PMID- 7727429
TI  - Bulge defects in intramolecular pyrimidine.purine.pyrimidine DNA triplexes in
      solution.
AB  - We report below on NMR studies of single base bulges in intramolecular pyrimidine
      (Y.RY) DNA triplexes in aqueous solution at acidic pH. The structural studies
      were undertaken with the goal of elucidating the dependence of the bulge site
      conformation on the nature of the base (adenine or thymine) and the location of
      the defect site (Watson-Crick pyrimidine and purine strands and Hoogsteen
      pyrimidine strand). The NMR parameters establish that an extra adenine loops out
      of the Y.RY triplex when it is positioned either on the Watson-Crick pyrimidine
      strand I (designated AI bulge triplex) or the Hoogsteen pyrimidine strand III
      (designated AIII bulge triplex) with the associated destabilization greater for
      the AIII bulge triplex relative to the AI bulge triplex. This observation that
      single adenine bulges loop out of Y.RY DNA triplexes contrasts with previous NMR
      structural studies, which established that single adenine bulges stack into DNA
      duplexes in solution. We also establish that an extra thymine on the Watson-Crick
      purine strand II (designated TII bulge triplex) loops out of a Y.RY DNA triplex.
      The single base bulges do not disrupt the pairing alignments of the flanking
      triples in all three bulge Y.RY triplexes. It therefore appears that structural
      constraints energetically disfavor stacking of extra bases into any of the three
      strands of Y.RY DNA triplexes in solution. Our NMR studies also establish that
      while intramolecular Y.RY DNA triplexes at low pH can accommodate single base
      bulges on each of the three strands, the triplex is disrupted following insertion
      of an A-G bulge in Hoogsteen strand III.

PMID- 7727430
TI  - Calorimetric detection of influenza virus induced membrane fusion.
AB  - Membrane fusion induced by the hemagglutinin glycoprotein of influenza virus has
      been extensively characterized, but the mechanism whereby the protein achieves
      the merger of the viral and target membrane lipids remains enigmatic. Various
      lipid intermediate structures have been proposed, and the energies required for
      their formation predicted. Here, we have analyzed the enthalpies of fusion of
      influenza with liposomes by titration calorimetry. If a small sample of virus in
      a weak neutral pH buffer was added to an excess of liposomes at low pH, a two
      component reaction was seen, composed of an exothermic reaction and a slower
      endothermic reaction. The exothermic reaction was the result of acid-base
      reactions between the neutral pH virus sample and low pH buffer and low-pH
      induced changes in the virus. The endothermic reaction was not observed in the
      absence of liposomes and much reduced if acid-inactivated virus, which had lost
      its fusion but not its binding activity, was added to liposomes. The endothermic
      reaction was more temperature dependent than the exothermic reaction; its pH
      dependence corresponded with that of fusion and its enthalpy was higher if fusion
      was more extensive. These data indicate that most of the endothermic reaction was
      due to membrane fusion. The experimentally determined enthalpy of fusion, 0.6-0.7
      kcal per mol of viral phospholipids, is much higher than expected on the basis of
      current theories about the formation of lipid intermediates during membrane
      fusion.

PMID- 7727431
TI  - Electron paramagnetic resonance evidence for a cysteine-based radical in pyruvate
      formate-lyase inactivated with mercaptopyruvate.
AB  - Pyruvate formate-lyase (PFL) is a glycyl radical-containing enzyme that catalyzes
      the reversible, nonoxidative conversion of pyruvate and CoA into acetyl-CoA and
      formate. The radical is located on the alpha-carbon of glycine 734 and is
      required for catalysis. Two cysteine residues, C418 and C419, are also essential
      for catalysis. Mercaptopyruvate, a biologically relevant pyruvate analog, is
      shown here to be a mechanism-based inactivator of PFL. Upon addition of
      mercaptopyruvate to active PFL, an EPR spectrum is generated which exhibits
      components from two sulfur-based radicals. For one of these radicals, a disulfide
      radical, the hyperfine coupling to a single beta-methylene hydrogen is resolved
      in features at g = 2.057 and 2.023. The effects of deuterium labeling of the
      enzyme on the EPR spectrum for this species are consistent with the new radical
      being on a cysteine residue, probably cysteine 418 or 419. This spectrum is not
      formed upon addition of the inactivator to mutant enzymes, C418S and C419S,
      indicating that both active site cysteines are required for formation of the new
      radicals. The identity of the second species is also ascribed to be a sulfur
      based radical on the basis of the EPR feature found at g = 2.01. Our results
      constitute the first direct evidence of sulfur-based radical formation in an
      enzyme. A mechanism for formation of the cysteine-based disulfide radical is
      proposed which requires the participation of the two active site cysteines as
      well as the glycyl radical.

PMID- 7727432
TI  - Side-chain determinants of beta-sheet stability.
AB  - beta-Sheet propensities of different amino acids depend on the context of both
      secondary and tertiary structure. In an attempt to establish general empirical
      relationships that determine this context dependence, we have determined the free
      energy of unfolding of a series of mutants at six positions in the beta-sheet of
      chymotrypsin inhibitor 2 (CI2). We have generated the series Val-->Ala-->Gly and
      Val<==>Thr at five positions, as well as the side-chain deletion Ile-->Val at
      residue 49 and Ala-->Gly at residue 77. In the series Val-->Ala-->Gly, the
      ranking order in terms of stability is Val > Ala > Gly at all positions. However,
      the change in free energy on deletion of methylene groups varies greatly. When
      Val and Thr are interchanged, the wild-type residue is always the more stable,
      but by a different amount at each position. We have attempted to rationalize the
      data by relating it to changes in solvent-accessible surface area, packing
      density, and statistically derived pseudo-energy functions that depend on phi,
      psi angles. There is no significant correlation of the energies with any of the
      variables except with the pseudo-energy function, but the deviations from these
      values are large. We conclude that thermodynamic scales for beta-sheet propensity
      are currently of insufficient precision for general design purposes, although
      they may be useful in special cases.

PMID- 7727433
TI  - Effect of heparin on the inhibition of factor Xa by tissue factor pathway
      inhibitor: a segment, Gly212-Phe243, of the third Kunitz domain is a heparin
      binding site.
AB  - Tissue factor pathway inhibitor (TFPI) inhibits the tissue factor--factor VIIa
      complex and factor Xa with its first and second Kunitz domains (K1 and K2),
      respectively. The inhibitory activity is enhanced by heparin, and the C-terminal
      basic part has been shown to be a heparin-binding site (HBS-1). To characterize
      and localize a second heparin-binding site (HBS-2), we studied the effect of
      heparin on the inhibitory activity of two forms of recombinant human TFPI, the
      full-length TFPI (rTFPI), and TFPI lacking the C-terminal basic part (rTFPI-C),
      by assaying the inhibition of human factor Xa. rTFPI-C inhibited factor Xa with
      an initial Ki of 6.79 nM in the absence of Ca2+ and 22.3 nM in the presence of 5
      mM CaCl2. Heparin decreased the initial Ki to 1.79 nM in the absence of Ca2+ and
      2.68 nM in the presence of 5 mM CaCl2, indicating the presence of HBS-2 in rTFPI
      C. The dissociation constant for the binding of HBS-2 with heparin was determined
      to be 830 nM using fluorescein-labeled heparin and rTFPI-C. Heparin enhanced the
      inhibitory activity of a fragment consisting of the K2 and K3 domains, but it did
      not stimulate the inhibitory activity of the K2 domain. A synthetic peptide
      mimicking from Gly212 to Phe243 in the K3 domain reduced the effect of heparin on
      the inhibition by rTFPI-C and rTFPI. These results defined the location of HBS-2
      in the basic region of the K3 domain between Gly212 and Phe243.

PMID- 7727434
TI  - Complementation of fragments of triosephosphate isomerase defined by exon
      boundaries.
AB  - Chicken triosephosphate isomerase (TIM) has been fragmented by inserting single
      "splits" at three separate exon/exon boundaries, and the complexes have been
      assayed for catalytic activity. In vivo studies show that the expression of both
      portions of each of the three different split genes complements the TIM
      deficiency of Escherichia coli strain DF502 when grown on selective media. The
      expression of only one fragment of each split gene does not complement the TIM
      minus genotype. To assess the catalytic activity that derives from the fragmented
      protein complex, the individual peptide products of one of the three split genes
      were expressed and purified. The purified complex showed isomerase activity,
      albeit of low specific catalytic activity. A catalytically active multichain
      complex composed of separate peptide products of a gene singly split at exon/exon
      junctions has thus been created.

PMID- 7727435
TI  - Structure of zinc-substituted cytochrome c: nuclear magnetic resonance and
      optical spectroscopic studies.
AB  - Optical and proton nuclear magnetic resonance (NMR) studies were carried out to
      assess the structure of the polypeptide chain and metal ligation in zinc
      substituted horse heart cytochrome c (Zn Cyt c). The 1D- and 2D-NMR (COSY, TOCSY,
      and NOESY) spectra allowed the assignment of proton resonances in 67 amino acid
      residues. These residues arose from all structural elements of the protein, alpha
      helices, beta-turns, and segments of the protein with no defined secondary
      structure. Small deviations of the chemical shifts of Zn Cyt c proton resonances
      from native Fe(II) Cyt c of less than 0.1 ppm are due to not fully matching
      solvent conditions. Differences in the chemical shifts between the two proteins
      in the range 0.10-0.20 ppm are not clustered and are observed not only in the
      vicinity of the Zn porphyrin but also on distant surface locations of the
      cytochrome. The resonance positions of the bridge protons, from the thioether
      bonds of the porphyrin with Cys 14 and Cys 17, were conserved in Zn Cyt c.
      Similarly, the Met 80 and His 18 protons had chemical shifts supporting the
      proposal that His 18 and Met 80, as for Fe(II) Cyt c, may provide the axial
      ligation in the Zn protein and that zinc may be in an unusual hexacoordinated
      geometry. Chemical shifts from proton resonances of alternative axial ligands of
      misfolded cytochrome like His 33, Lys 79, and Phe 82 were found to be the same as
      in the Fe(II) protein, excluding the possibility of their axial ligation to Zn.
      The His 18-Zn-Met 80 ligation was also consistent with data from absorption and
      luminescence studies. We conclude that Zn Cyt c is an adequate structural model
      for Fe(II) Cyt c as both share the same overall structure, including axial
      ligands, environment in the porphyrin vicinity, and the same binding interface
      with redox partners.

PMID- 7727436
TI  - Vitamin E oxidation in rat liver mitochondria.
AB  - Antioxidant reactions of alpha-tocopherol (vitamin E, alpha-TH) were studied by
      examining the fate of alpha-TH during oxidative challenge to mitochondrial
      membranes. Rat liver mitochondria were exposed to increasing concentrations of
      the water-soluble radical initiator 2,2'-azobis(2-amidinopropane) dihydrochoride
      (ABAP), and damage was assessed by monitoring mitochondrial respiration, alpha-TH
      oxidation, and lipid peroxidation. Significant lipid peroxidation was observed
      after 50% of the initial alpha-TH was depleted. Oxidative damage produced by ABAP
      generated peroxyl radicals inhibited mitochondrial use of O2, as indicated by
      decreases in the respiratory control ratio and in state 3 and state 4
      respiration. Rat liver mitochondria were supplemented with [14C]-alpha-TH by
      incubation of liver homogenate with [14C]-alpha-TH for 30 min at room
      temperature, followed by isolation of mitochondria by differential
      centrifugation. This supplementation resulted in a distribution of 83.7% and
      14.3% of the added alpha-TH to the inner and outer mitochondrial membranes,
      respectively, which is similar to the distribution of endogenous alpha-TH. [14C]
      alpha-TH-supplemented mitochondria then were treated with ABAP, and alpha-TH
      oxidation products were identified by radiochromatographic analysis of
      mitochondrial extracts. Products observed included alpha-tocopherolquinone, alpha
      tocopherolquinone-2,3-oxide, and alpha-tocopherolquinone-5,6-oxide, which were
      identified by comparing HPLC retention and UV spectra to those of authentic
      standards. Product identities were verified by GC-MS of product O-trimethylsilyl
      derivatives. Another product, which was identified by HPLC, UV, and mass spectral
      analysis as 8a-(ethyldioxy)tocopherone, was found to be an artifact of sample
      workup and was shown to be derived from 8a-hydroperoxytocopherone, which was
      formed by alpha-TH oxidation in the mitochondria. These results indicate that
      alpha-TH antioxidant reactions in mitochondria are similar to those identified in
      homogeneous solutions and model liposomal systems.

PMID- 7727437
TI  - Aggregation and precipitation of human relaxin induced by metal-catalyzed
      oxidation.
AB  - The interactions of proteins with reactive oxygen species may result in covalent
      modifications of amino acid residues in proteins and possible alterations of
      protein conformation. In an attempt to elucidate the mechanisms of the metal
      catalyzed oxidation of human relaxin, we employed ascorbic acid/transition metal
      ion [Cu(II) or Fe(III)]/O2 as a model oxidizing system. Experimental results
      indicated selective oxidation of His and Met residues and rapid formation of
      aggregates (noncovalent, pH dependent) following the oxidation reaction. Amino
      acid analysis and LC/MS data following tryptic digestion demonstrated the
      oxidation of the His A(12) residue, which resulted in 2-oxohistidine and some
      other unidentified degradation products. The oxidation of both Met residues to
      Met-sulfoxides was also identified, and it was found that Met B(4) was more
      easily oxidized than Met B(25). The comparative kinetic studies of two Met
      containing fragments of relaxin suggested that the preferred oxidation of Met
      B(4) is due to its close proximity to some metal-binding neighboring amino acid
      residues. These covalent alterations may lead to the modification of secondary
      and tertiary structure and increase the exposure of the hydrophobic surface of
      the protein which eventually induces aggregation of precipitation. The
      modification of relaxin by ascorbic acid/CuCl2 solution could be totally
      inhibited by the presence of EDTA. In contrast, catalase and superoxide dismutase
      showed no effects on the oxidation process.

PMID- 7727438
TI  - Comparing the refolding and reoxidation of recombinant porcine growth hormone
      from a urea denatured state and from Escherichia coli inclusion bodies.
AB  - Overexpression of cloned genes in bacteria often leads to insoluble refractile
      body formation requiring solubilization and refolding to obtain biologically
      active proteins. A refolding pathway was established for a model protein, porcine
      growth hormone (PGH), yielding an appreciably high recovery of 85%. The
      conditions include the dilution of a urea, beta-mercaptoethanol (beta-ME)
      denatured PGH solution in a refolding environment containing 3.5 M urea and 10 mM
      beta-ME/HED at a 10:1 ratio at pH 9.1 and 0.5 mg/mL PGH. The intrinsic
      fluorescence-detected transition of PGH in urea gives 3.8 kcal/mol for the free
      energy of denaturation (delta GH2O) of PGH. The native-like conformation of PGH
      is dependent on disulfide bonds because reduced and carboxymethylated PGH is
      devoid of tertiary structure as assessed by intrinsic tryptophan fluorescence.
      Physical analysis of C-terminally truncated recombinant PGH indicated no
      significant difference in the free energy of denaturation of P-band in urea as
      full-length PGH. This suggests that the first disulfide, forming the large loop
      domain of PGH, provides a significantly greater contribution to the
      conformational stability of PGH than the second disulfide, which forms the
      carboxy-terminal small loop domain. The rate of formation of native structure
      during refolding was biphasic, with native structure identified by intrinsic
      fluorescence and hydrophobicity spectroscopy prior to disulfide bond formation.
      Thus "framework" intermediates are prerequisites for correct disulfide formation
      and tertiary folding of PGH. This study shows how a protein refolds, forms
      disulfides, and self-associates, which may be useful for examining the refolding
      of other recombinant proteins.

PMID- 7727439
TI  - Structure of a compact peptide from staphylococcal nuclease determined by
      circular dichroism and NMR spectroscopy.
AB  - Compact regions in proteins are thought to correspond to domains. If this is
      true, the structure of a compact region excised from a protein should closely
      resemble the structure in the intact protein. To test this theory, a compact
      peptide corresponding to residues 129-142 of staphylococcal nuclease (Ac
      EAQAKKEKLNIWS-NH2) was synthesized and its solution structure determined using
      circular dichroism (CD) and 2D NMR. In aqueous solution, the peptide exhibits CD
      spectra characteristic of a nascent helix. This nascent helical structure is
      stabilized by the addition of 2,2,2-trifluoroethanol. Under these conditions, the
      chemical shift indexes of the 1H alpha and 13C alpha resonances, temperature
      coefficients of amide protons, and NOE constraints are all consistent with the
      peptide's structure being a helix-turn. This structure is almost identical to
      that found in the intact protein.

PMID- 7727440
TI  - Catalytic characterization of 4a-hydroxytetrahydropterin dehydratase.
AB  - The cofactor product of the aromatic amino acid hydroxylases, 4a-hydroxy-6(R)
      tetrahydrobiopterin, requires dehydration before tetrahydrobiopterin can be
      regenerated by dihydropteridine reductase. Carbinolamine dehydration occurs
      nonenzymatically, but the reaction is also catalyzed by 4a
      hydroxytetrahydropterin dehydratase. This enzyme has the identical amino acid
      sequence to DCoH, the dimerization cofactor of the transcription regulator, HNF-1
      alpha. The catalytic activity of rat liver dehydratase was characterized using a
      new assay employing chemically synthesized 4a-hydroxytetrahydropterins. The
      enzyme shows little sensitivity to the structure or configuration of the 6
      substituent of its substrate, with Km's for 6(S)-methyl, 6(R)-methyl, 6(S)
      propyl, and 6(R)-L-erythro-dihydroxypropyl all between 1.5 and 6 microM. Turnover
      numbers at 37 degrees C are 50-90 s-1 at pH 7.4 and 2.5-3-fold lower at pH 8.4.
      Both 4a(R)- and 4a(S)-hydroxytetrahydropterins are good substrates. The quinoid
      dihydropterin products are strong inhibitors of the dehydratase with KI's about
      one half of their respective Km's, but no inhibition was observed with 7,8
      dihydropterins or tetrahydropterins. The enzyme contains no metals and no
      phosphorus. Reaction mechanisms which involve either acid and/or base catalysis
      are discussed. 4a-Hydroxy-6(R)-tetrahydrobiopterin was determined not to be a
      product inhibitor of phenylalanine hydroxylase. It is concluded that the
      dehydratase (which was found to be 6 microM in rat liver) is essential in vivo to
      prevent rearrangement of 4a-hydroxy-6(R)-tetrahydrobiopterin and to maintain the
      supply of tetrahydrobiopterin cofactor for the hydroxylases under conditions
      where the nonenzymatic rate would be inadequate.

PMID- 7727441
TI  - Activation and characterization of procarboxypeptidase B from human plasma.
AB  - Recently we reported the isolation and cloning of a novel plasma
      procarboxypeptidase B that binds plasminogen [Eaton, D. L., Malloy, B. E., Tsai,
      S. P., Henzel, W., & Drayna, D. (1991) J. Biol. Chem. 266, 21833-21838]. This
      plasma procarboxypeptidase is structurally similar to tissue
      procarboxypeptidases, and initial substrate studies showed that this plasma
      protein behaves like a basic carboxypeptidase and is now known as human plasma
      procarboxypeptidase B (pro-pCPB). However, unlike the tissue
      procarboxypeptidases, pro-pCPB is extremely unstable to trypsin activation.
      Trypsin cleaves pro-pCPB at two sites: Arg-92 and Arg-330. Cleavage at Arg-92
      releases the activation peptide and generates an active enzyme. However, cleavage
      at Arg-330 inactivates pCPB. This renders the characterization of pCPB difficult.
      We have found that 6-amino-n-hexanoic acid (epsilon ACA), a compeptitive
      inhibitor of basic carboxypeptidases, selectively limits trypsin cleavage of pro
      pCPB. In the presence of epsilon ACA, trypsin cleavage at Arg-330 is
      significantly limited while the cleavage at Arg-92 is unaffected. Using this
      approach, active pCPB can now be obtained. Kinetic characterization shows that
      pCPB behaves like other known basic carboxypeptidases. pCPB is more specific for
      substrates with C-terminal arginine than those with C-terminal lysine for all the
      natural and synthetic peptides tested. It also hydrolyzes the synthetic ester
      substrate more efficiently than the synthetic peptide substrate, especially at
      high pH. The active site Zn2+ can be replaced with other metals with change in
      substrate specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727442
TI  - Chloride effect on the early photolysis intermediates of a gecko cone-type visual
      pigment.
AB  - Nanosecond laser photolysis measurements were conducted on the cone-type visual
      pigment P521 in digitonin extracts of Tokay gecko (Gekko gekko) retina containing
      physiological chloride ion levels and also on samples which had been chloride
      depleted or which contained high levels (4 M) of chloride. Absorbance difference
      spectra were recorded at a sequence of time delays from 30 ns to 60 microseconds
      following excitation with a pulse of either 532- or 477-nm actinic light. Global
      analysis showed the kinetic decay data for gecko pigment P521 to be best fit by
      two exponential processes under all chloride conditions. The initial photoproduct
      detected had a broad spectrum characteristic of an equilibrated mixture of a
      Batho P521 intermediate with its blue-shifted intermediate (BSI P521) decay
      product. The first exponential process was assigned to the decay of this mixture
      to the Lumi P521 intermediate. The second exponential process was identified as
      the decay of Lumi P521 to Meta I P521. The initial photoproduct's spectrum
      exhibited a strong dependence on chloride concentration, indicating that chloride
      affects the composition of the equilibrated mixture of Batho P521 and BSI P521.
      These results suggest that the affinity for chloride is reduced approximately 5
      fold in the Batho P521 intermediate and approximately 50-fold in the BSI P521
      intermediate. Chloride concentration also affects the apparent decay rate of the
      equilibrated mixture. When the apparent decay rate is corrected for the
      composition of the equilibrated mixture, a relatively invariant microscopic rate
      constant is obtained for BSI decay (k = 1/55 ns-1).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7727443
TI  - Electron transfer between cytochrome c and the isolated CuA domain:
      identification of substrate-binding residues in cytochrome c oxidase.
AB  - Subunit II of cytochrome c oxidase has a C-terminal domain that is exposed to
      aqueous solution on membrane surface and contains a copper center called CuA. The
      central part of the cytochrome c binding site is thought to reside in this
      domain. We have expressed the subunit II fragment of the Paracoccus denitrificans
      cytochrome c oxidase in a soluble form and studied its interaction with
      cytochrome c by stopped-flow spectroscopy. The oxidation of cytochrome c by the
      CuA domain follows monophasic kinetics, indicating the presence of a single
      kinetically competent binding site. In low ionic strength medium, the domain
      oxidizes Paracoccus cytochrome c-550 and horse mitochondrial cytochrome c at the
      rates of 1.5 x 10(6) and 3 x 10(5) M-1 s-1, respectively. The reaction rates are
      strongly dependent on ionic strength, which must reflect electrostatic
      interactions within the complex. The KD for the complex between the bacterial
      cytochrome c and the domain is 1.6 microM; i.e., it is similar to that between
      the mitochondrial cytochrome c and the intact oxidase, suggesting that both
      contain the same catalytically competent binding site. Using site-directed
      mutagenesis, we have identified five conserved residues of the CuA domain that
      are involved in the cytochrome c binding. Mutations of glutamine 148, glutamate
      154, aspartate 206, aspartate 221, or glutamate 246 lead to a 35-85% decrease in
      the rate of cytochrome c oxidation. The simultaneous substitution of three
      invariant carboxylic acids (aspartate 206, aspartate 221, and glutamate 246)
      leads to a 95% decrease in the reaction rate. Conversely, the reaction can be
      enhanced by removing a positive charge (lysine 219) from the CuA domain.

PMID- 7727444
TI  - Enthalpy of antibody--cytochrome c binding.
AB  - High-sensitivity titration calorimetry is used to measure changes in enthalpy,
      heat capacity, and protonation for binding of two monoclonal antibodies (MAbs) to
      topologically distinct surfaces of cytochrome c. MAb 2B5 binds near the exposed
      heme crevice in a reaction involving proton uptake, while there is no change in
      protonation for MAb 5F8 binding to the opposite side of the molecule. Both
      antibodies have association rate constants with the activation enthalpy and
      viscosity dependence expected of diffusion-limited reactions [Raman et al. (1992)
      Biochemistry 31, 10370-10379], and bind with high affinity (delta Gzerob = -12.6
      kcal mol-1 for MAb 2B5 and -13.9 kcal mol-1 for MAb 5F8, at pH 7, 25 degrees C).
      At 25 degrees C, the equilibrium enthalpy and entropy contributions to the free
      energy of binding are negative for both antibodies (delta Hzerob = -21.0 kcal mol
      1, delta Szerob = -28.2 cal mol-1 K-1 for MAb 2B5; and delta Hzerob = -21.7 kcal
      mol-1, delta Szerob = 26.3 cal mol-1 K-1 for MAb 5F8). The enthalpy of MAb 2B5
      cytochrome c association exhibits a marked temperature dependence (delta Cp = 
      580 cal mol-1 K-1), but the enthalpy for MAb 5F8 binding is much less dependent
      on temperature (delta Cp = -172 cal mol-1 K-1). The large differences in delta Cp
      for binding of the two antibodies suggest corresponding differences in the mode
      of binding, or in the molecular surfaces buried in the binding reactions. In
      particular, factors other than hydrophobic effects may be significant
      contributors to the thermodynamics of antibody-cytochrome c binding, especially
      when delta Cp is small (MAb 5F8).

PMID- 7727445
TI  - Amino acid residues that influence the binding of manganese or calcium to
      photosystem II. 1. The lumenal interhelical domains of the D1 polypeptide.
AB  - To identify amino acid residues that ligate the manganese and calcium ions of
      photosystem II or that are otherwise crucial to water oxidation, site-directed
      mutations were constructed in the unicellular cyanobacterium Synechocystis sp.
      PCC 6803 at all conserved carboxylate, histidine, and tyrosine residues in the
      lumenal interhelical domains of the D1 polypeptide. Mutants with impaired
      photoautotrophic growth or oxygen evolution were characterized in vivo by
      measuring changes in the yield of variable chlorophyll a fluorescence after a
      saturating flash or brief illumination given in the presence of an electron
      transfer inhibitor or following each in a series of saturating flashes given in
      the absence of inhibitor [Chu, H.-A., Nguyen, A. P., & Debus, R. J. (1994)
      Biochemistry 33, 6137-6149]. Mutants were also characterized after propagation in
      media having other cations substituted for calcium. We conclude that Asp-59 and
      Asp-61 may ligate calcium, that Asp-59, Asp-61, Glu-65, and His-92 influence the
      properties of the manganese cluster without significantly affecting its stability
      or ability to assemble, that Glu-189 plays an important structural role in
      maintaining the catalytic efficiency of the Mn cluster and partly influences the
      cluster's stability or ability to assemble, that His-92 and Glu-189 influence the
      binding of calcium, and that His-190 strongly influences the redox properties of
      the secondary electron donor, YZox, and either ligates manganese or serves as a
      crucial base or hydrogen bond donor. In addition, we conclude that Asp-170 may
      ligate manganese, but that its replacement with Val, Leu, or Ile causes
      structural perturbations that partly compensate for the loss of the carboxylate
      moiety.

PMID- 7727446
TI  - Amino acid residues that influence the binding of manganese or calcium to
      photosystem II. 2. The carboxy-terminal domain of the D1 polypeptide.
AB  - To identify amino acid residues that ligate the manganese and calcium ions of
      photosystem II or are otherwise crucial to water oxidation, site-directed
      mutations were constructed in the unicellular cyanobacterium Synechocystis sp.
      PCC 6803 at all conserved carboxylate and histidine residues in the carboxy
      terminal domain of the D1 polypeptide. Mutants with impaired photoautotrophic
      growth or oxygen evolution were characterized in vivo by measuring changes in the
      yield of variable chlorophyll a fluorescence after a saturating flash or brief
      illumination given in the presence of an electron-transfer inhibitor or following
      each in a series of saturating flashes given in the absence of inhibitor [Chu, H.
      A., Nguyen, A. P., & Debus, R.J. (1994) Biochemistry 33, 6137-6149]. Mutants were
      also characterized after propagation in media having other cations substituted
      for calcium. We conclude that His-332 Glu-333, His-337, and Asp-342 influence the
      assembly and/or stability of the manganese cluster, that His-332, Glu-333, and
      His-337 may ligate manganese, that Asp-342 may ligate manganese, calcium, or
      both, that Glu-333 and Asp-342 may play important structural roles, and that His
      332, Glu-333, and His-337 influence the binding of calcium, although Glu-333 is
      unlikely to ligate Ca2+ directly. Several His-332, Glu-333, His-337, and Asp-342
      mutants were very light sensitive, possibly because toxic activated oxygen
      species were released from altered or partly assembled manganese clusters.
      Finally, mutations at Asp-342 do not prevent posttranslational cleavage of the
      carboxy-terminal extension of the D1 polypeptide's precursor form in vivo.

PMID- 7727447
TI  - Studies of the heme coordination and ligand binding properties of soluble
      guanylyl cyclase (sGC): characterization of Fe(II)sGC and Fe(II)sGC(CO) by
      electronic absorption and magnetic circular dichroism spectroscopies and failure
      of CO to activate the enzyme.
AB  - The mechanism of activation of soluble guanylyl cyclase by NO is poorly
      understood although it is clear that NO interacts with a heme group in the
      protein via formation of a heme-nitrosyl adduct. The objective of this study is
      to investigate the coordination environment of the heme in the enzyme
      spectroscopically in the presence of known heme ligands and to correlate the
      spectral characteristics with other heme proteins of known structure. Comparison
      of the electronic and magnetic circular dichroism (MCD) spectra for ferrous
      bovine soluble guanylyl cyclase (Fe(II)sGC) in the absence and presence of the
      common heme ligand CO with those of other hemoproteins suggests that histidine is
      an axial ligand to the heme iron in Fe(II)sGC. Further analysis indicates that
      Fe(II)sGC is predominantly bis-histidine ligated; the ratio of MCD signal
      intensity in the visible region to that in the Soret region is most consistent
      with an admixture of pentacoordinate and hexacoordinate ferrous heme in Fe(II)sGC
      at pH 7.8. Spectral changes upon CO binding have been correlated with the
      activity of the enzyme to determine the relationship between coordination
      structure and activity. Although CO clearly binds to Fe(II)sGC to form a six
      coordinate adduct, it fails to significantly activate the enzyme regardless of
      heme content or CO concentration. In contrast, the extent of activation of sGC by
      NO is dependent on the heme content in the enzyme and on the concentration of NO.
      These observations are consistent with a mechanism for activation of soluble
      guanylyl cyclase in which the bond between the heme iron and the proximal
      histidine must be broken for activation to take place.

PMID- 7727448
TI  - NMR assignment of Rhodobacter capsulatus ferricytochrome c', a 28 kDa
      paramagnetic heme protein.
AB  - The cytochromes c' are paramagnetic heme proteins generally consisting of two
      identical 14 kDa subunits. The 1H and 15N resonances of the ferricytochrome c'
      from the purple phototrophic bacterium Rhodobacter capsulatus have been
      extensively assigned by the TOCSY-HSQC, NOESY-HSQC, HSQC-NOESY-HSQC, and HNHA 3D
      heteronuclear experiments performed on an 8 mM sample labeled with 15N. In
      addition, the 13C alpha and 13CO resonances were assigned by the HNCA and
      multiple-quantum HNCOCA 3D experiments performed on a 0.5 mM sample labeled with
      13C and 15N. The assignment of the backbone 13C resonances was used to confirm
      the 1H and 15N assignments and to better define secondary structure. On the basis
      of medium-range NOEs, 3JHN alpha coupling constants, and backbone 13C chemical
      shifts, the secondary structure consists of four helices: helix-1 (3-29), helix-2
      (33-49), helix-3 (78-97), and helix-4 (103-117). On the basis of long-range NOE
      contacts, the Rb. capsulatus ferricytochrome c' is a four-helix bundle protein in
      which consecutive helices are antiparallel with respect to one another.

PMID- 7727449
TI  - Solution structure of the conserved segment of the Myb cognate DNA sequence by 2D
      NMR, spectral simulation, restrained energy minimization, and distance geometry
      calculations.
AB  - Solution structure of a self-complementary DNA duplex d-ACCGTTAACGGT containing
      the TAACGG recognition segment of Myb protein has been obtained by NMR
      spectroscopy. Complete resonance assignments of all the protons (except H5', H5"
      protons) have been obtained following standard procedures based on two
      dimensional NMR techniques. Using a total of 72 coupling constants, and 95 NOE
      intensities, restrained energy minimization has been carried out, with the X-PLOR
      force field. The distance constraint set has been iteratively refined, for better
      fits with experimental NOE intensities. Using the final constraint set thus
      obtained, and explicit H-bond constraints for A.T, G.C base pairs in the duplex,
      distance geometry calculations have been carried in the torsion angle space with
      the program TANDY-2S to identify the family of structures consistent with the NMR
      data. We observe that the constraint set does indeed define a unique structure
      for the DNA segment. The structural details have been analyzed, and the sequence
      dependent variations in torsion angles, base pair geometries, and helicoidal
      parameters have been documented. We observed that the helix axis displays a
      nonregular path, and three centered H-bonds have been seen at AA, AC, and CC
      steps in the major groove of the helix. Substantial variations have been observed
      for the helix axis and the groove widths at the recognition site. The base pairs
      exhibit high negative propeller twists. The structure is characterized by O4'
      endo geometry for all the sugar rings (expect G10), and the other torsion angles
      belong to the B-DNA families.

PMID- 7727450
TI  - NMR and restrained molecular dynamics study of the three-dimensional solution
      structure of toxin FS2, a specific blocker of the L-type calcium channel,
      isolated from black mamba venom.
AB  - The three-dimensional solution structure of toxin FS2, a 60-residue polypeptide
      isolated from the venom of black mamba snake (Dendroaspis polylepis polylepis),
      has been determined by nuclear magnetic resonance spectroscopy. Using 600 NOE
      constraints and 55 dihedral angle constraints, a set of 20 structures obtained
      from distance-geometry calculations was further refined by molecular dynamics
      calculations using a combined simulated annealing-restrained MD protocol. The
      resulting 20 conformers, taken to represent the solution structure, give an
      average rmsd of 1.2 A for their backbone atoms, relative to the average
      structure. The overall resulting three-fingered structure is similar to those
      already observed in several postsynaptic neurotoxins, cardiotoxins, and
      fasciculins, which all share with toxin FS2 the same network of four disulfide
      bridges. The overall concavity of the molecule, considered as a flat bottomed
      dish, is oriented toward the C-terminal loop of the molecule. This orientation is
      similar to that of fasciculins and cardiotoxins but opposite to that of
      neurotoxins. On the basis of the local rms displacements between the 20
      conformers, the structure of the first loop appears to be less well defined in
      FS2 than in the previously reported neurotoxin structures, but fasciculin 1 shows
      a similar trend with particularly high temperature factors for this part of the X
      ray structure. The concave side which presents most of the positively charged
      residues is quite similar in FS2 and fasciculin 1. The main difference is shown
      by the convex side of the third loop, mostly hydrophobic in FS2, in contrast to
      the pair of negatively charged aspartates in fasciculin 1. This difference could
      be one of the factors leading to the distinct pharmacological properties-L-type
      calcium channel blocker for FS2 and cholinesterase inhibitor for fasciculin-
      observed for these two subgroups of the "angusticeps-type" toxins.

PMID- 7727451
TI  - 2D 1H-NMR conformational study of phosphatidylserine diluted in perdeuterated
      dodecylphosphocholine micelles. Evidence for a pH-induced conformational
      transition.
AB  - The conformation of phosphatidylserine (DMPS) diluted in perdeuterated
      dodecylphosphocholine micelles (DPC) has been investigated by 1D and 2D proton
      NMR spectroscopy. Chemical shift pH dependence showed that the pK relative to the
      serine carboxyl titration (3.4 +/- 0.05) was nearly identical to that measured in
      bilayers. Chemical shift and NOE data revealed that the phosphatidylserine
      molecule undergoes a conformational transition upon titration of the serine
      carboxyl group. The NOE network observed between the different parts of the
      molecule was sufficiently abundant to allow, in combination with molecular
      modeling methods, an assessment of the conformational changes. The conformational
      changes mainly involve the glycerol backbone, which is parallel to the whole
      molecule, that is, to the layer normal, at low pH and becomes perpendicular to
      the whole molecule at neutral pH. In both cases, the conformations are remarkably
      close to those observed for the crystal forms of zwitterionic and negatively
      charged phospholipids. Two-dimensional proton NMR study of phospholipids, diluted
      in perdeuterated DPC micelles, appears to be a simple and relevant method to
      obtain complete and direct information on their conformations in a model membrane
      solution interface.

PMID- 7727452
TI  - Structure and polarity of mouse brain synaptic plasma membrane: effects of
      ethanol in vitro and in vivo.
AB  - Structural and dielectric alteration by ethanol in vitro and chronic ethanol
      consumption were examined in synaptic plasma membranes (SPM) using
      diphenylhexatriene and charged diphenylhexatriene derivatives. These
      fluorophores, in combination with multifrequency phase and modulation
      fluorometry, allowed the examination of the surface and interior core of SPM.
      Limiting anisotropy and rotational relaxation time demonstrated that the
      synaptosomal plasma membrane surface domain was more rigid than the interior core
      domain. Ethanol in vitro fluidized the interior core and surface domains in SPM
      of the control, but not chronic ethanol-treated mice. Although the latter
      membranes were more rigid than control membranes, the intrinsic rigidity of the
      interior core of the synaptosomal plasma membrane did not strictly correlate with
      effects of ethanol in vitro. SPM of irradiated membranes were more rigid, but
      ethanol fluidized those membranes. Diphenylhexatriene lifetime and
      photoreactivity were sensitive to the range of dielectric constants in the SPM
      interior core. Ethanol in vitro increased both the surface and interior core
      range of dielectric constants of SPM from control but not chronic ethanol-treated
      animals. Thus, ethanol in vitro altered not only the fluidity but also the range
      of dielectric constants in both the surface and interior core domains in SPM of
      control but not chronic ethanol-treated mice.

PMID- 7727453
TI  - The human dopamine D5 receptor gene: cloning and characterization of the 5'
      flanking and promoter region.
AB  - Genomic and overlapping cDNA clones encompassing the entire 5'-untranslated
      region of the human D5 receptor gene were cloned and sequenced. Comparison of
      these human D5 receptor genomic and cDNA clones revealed the presence of two
      exons separated by a small and variably sized intron (of either 179 or 155 bp).
      We have determined that the major site of transcription initiation of the D5 gene
      is 2125 bp upstream from the translational initiation start site. The region 5'
      to the transcription initiation site lacked conventional TATA and CAAT sequences,
      but contained several putative binding sites for transcription factors, such as
      Sp1 and Ap1. Luciferase reporter gene constructs containing D5 gene sequence
      information up to 500 bp 5' of the transcription initiation site were able to
      stimulate transcription only in SK-N-SH cells but not in COS-7, CHO, P19EC,
      NB41A3, and SK-N-MC cell lines. Promoter deletion analysis indicated that the D5
      gene promoter contained a positive modulator at 119-182 and a negative modulator
      251-500 bases upstream from the site of transcription initiation. In addition, in
      order to detect the expression of functional D5 receptor mRNAs and not those of
      its expressed pseudogenes, in situ hybridization analysis of monkey and human
      brain using a 5' D5-specific riboprobe revealed that D5 receptor mRNA was most
      abundant in discrete cortical areas (layers II, IV, and VI), the dentate gyrus,
      and hippocampal subfields with very little message detected in the striatum.
      Unexpectedly, D5 mRNA antisense riboprobes labeled discrete cell bodies in the
      pars compacta of the substantia nigra. The characterization of the genomic
      organization of the D5 receptor gene and of those factors involved in its
      transcriptional regulation may aid in our understanding of the role this gene
      product plays in the generation and maintenance of dopamine D1-like receptor
      mediated events.

PMID- 7727454
TI  - Pressure- and thermally-induced reversible changes in the secondary structure of
      ribonuclease A studied by FT-IR spectroscopy.
AB  - Fourier transform infrared (FT-IR) spectroscopy combined with a resolution
      enhancement technique has been used to characterize pressure and thermal effects
      on the secondary structure of ribonuclease A. The experiments were performed at
      pD 7.0 with 50 mg/mL protein solution in D2O buffer. According to the observed
      changes in the amide I' band, secondary structure elements such as alpha-helices,
      beta-sheets, and turns are cooperatively disrupted by application of either
      pressures above 570 MPa at 30 degrees C or temperatures above 60 degrees C at 0.1
      MPa. Pressure- and thermally-denatured ribonuclease A are fully unfolded and do
      not contain any residual secondary structures. Both the structural changes are
      intrinsically reversible, although the pressure-induced transition shows a
      hysteresis. It is found that nonnative turn structures are formed prior to the
      appearance of the native secondary structure in the folding from the pressure
      unfolded state. The structural features upon the pressure-induced unfolding are
      additionally characterized by the interesting behavior of hydrogen-deuterium
      exchange at high pressure. Most of the backbone amide protons protected at
      atmospheric pressure, which are involved in the alpha-helices and beta-sheet, are
      exchanged with solvent deuterons in the pressure range where the two secondary
      structural elements are virtually identified as intact. There is a possibility
      that, for ribonuclease A, application of high pressure up to 570 MPa induces such
      a partially unfolded state as has native-like secondary structure but permits
      solvent to be highly accessible to the internal regions.

PMID- 7727455
TI  - Thermodynamic studies of the core histones: ionic strength and pH dependence of
      H2A-H2B dimer stability.
AB  - The thermal stability of the core histone dimer H2A-H2B has been studied by high
      sensitivity differential scanning calorimetry and circular dichroism
      spectroscopy. The unfolding transition temperature of the 28 kDa H2A-H2B dimer
      increases as a function of both the ionic strength of the solvent and the total
      protein concentration. At neutral pH and physiological ionic strength, the
      thermal denaturation is centered at about 50 degrees C with a corresponding
      enthalpy change of about 40 kcal/mol of 14 kDa monomer unit and an excess heat
      capacity of about 1.4 kcal/(K.mol) of 14 kDa monomer unit. The H2A-H2B dimer is
      stable mainly between pH 5.5 and 10.5. Below pH 4.0, the system is unfolded at
      all temperatures. The thermodynamic analysis is performed at low ionic strength
      where almost complete reversibility is attained, since higher salt conditions
      seem to promote aggregation and irreversibility of the transitions. Analysis of
      the data shows that at low ionic strength and pH values between 6.5 and 8.5, the
      H2A-H2B dimer behaves as a highly cooperative system, melting as a single unit
      without any detectable intermediates of dissociated, yet folded, H2A and H2B
      monomers. This is consistent with the observed protein concentration dependence
      of the midpoint of the thermal denaturation. The two-state unfolding process can
      be described by the general scheme AB-->2U, indicating that the individual H2A
      and H2B polypeptides are folded, stable entities only when complexed as the H2A
      H2B dimer and that the major contribution to the stabilization of the dimer
      derives from the coupling between the H2A and H2B interfaces.

PMID- 7727456
TI  - Tennessee Council of Deans & Directors Career Mobility Plan.

PMID- 7727457
TI  - Meet the Governor--Don Sundquist. Interview by Anita Napier.

PMID- 7727458
TI  - Cellular and molecular mechanisms of human cardiac myocyte injury after
      transplantation.
AB  - BACKGROUND: Fetal human cardiac myocytes or a cell line derived from fetal human
      cardiac myocytes, termed W1, even after experimental induction of "normal" levels
      of major histocompatibility complex class I and II antigens, fail to induce the
      activation of primary allogeneic responses. Therefore, our laboratory has
      investigated the ability of such MHC-expressing cardiac myocytes to induce
      secondary alloproliferative responses or to serve as target cells for cytotoxic T
      lymphocytes. METHODS: Cloned CD4+ and CD8+ T-cell lines having specificity for
      major histocompatibility complex class I and II molecules expressed by the fetal
      human cardiac myocytes and the W1 cell line were used in standard proliferation
      and cytotoxicity assays. RESULTS: Our data show that none of the 19 HLA-DR3 (beta
      1 0301)- or HLA-DR15 (beta 1 1501)-specific CD4+ cloned T-cell lines reacted with
      HLA-DR3- or DR15-expressing W1 or fetal human cardiac myocytes. However, these
      CD4+ T cells did react, as expected, with similar HLA-DR3/DR15-expressing
      homozygous typing cells. Of the 16 cloned CD8+ cytotoxic T lymphocytes with
      specificity for HLA-A2 and the 12 with specificity for HLA-A1, only two of each
      showed weak cytotoxicity against interferon gamma-pretreated HLA-A2 and A1
      expressing W1 and fetal human cardiac myocytes, respectively. Each cloned
      cytotoxic T lymphocytes line, however, was very effective against HLA-A2 and A1
      expressing homozygous typing cells. Although the IFN-gamma-induced W1 and fetal
      human cardiac myocytes were not susceptible to cytotoxic T lymphocytes-mediated
      lysis, they were capable of inhibiting specific cytotoxic T lymphocytes function
      as defined by cold target inhibition studies. CONCLUSIONS: These data suggest
      that peptide-allo major histocompatibility complex presented by human
      cardiomyocytes is recognized by T cells and the these lymphocyte/myocyte
      interactions lead to immunologic ignorance.

PMID- 7727459
TI  - Allograft diastolic dysfunction and chronotropic incompetence limit cardiac
      output response to exercise two to six years after heart transplantation.
AB  - BACKGROUND: Because prolonged survival of heart transplant recipients is expected
      with the current immunosuppressive treatment, the functional capacity of these
      long-term survivors is of interest. Previous exercise studies showed no objective
      improvement in exercise tolerance several years after transplantation, but the
      extent to which chronotropic incompetence and allograft diastolic dysfunction
      observed early after transplantation may improve over time has not been defined.
      METHODS: Thirteen untrained heart transplant recipients without symptoms, between
      27 and 70 months after transplantation, and 13 age-matched sedentary normal
      controls underwent maximal upright bicycle exercise testing with simultaneous
      hemodynamic, radionuclide, and expired gas measurements. RESULTS: Systolic
      function as measured by ejection fraction was supranormal at rest in the
      transplant group and normalized with exercise. Despite their maximal exercise
      effort, transplant recipients had a 60% reduction in their exercise capacity
      compared with nontransplant recipients. Peak oxygen consumption was similarly
      reduced by 52%. Cardiac output response to exercise was 43% lower in the
      transplant group because of a 78% reduction in heart rate reserve and an 18%
      reduction in maximal stroke volume. Ventricular volumes were similarly reduced
      after transplantation, but filling pressures remained normal, indicating
      allograft diastolic dysfunction. Despite the significantly reduced maximal
      cardiac output, maximal arteriovenous oxygen difference was 25% lower in the
      transplant recipients, suggesting a peripheral deficit in oxygen handling.
      CONCLUSIONS: Therefore, patients, 2 to 6 years after transplantation, continue to
      have a significant reduction in exercise tolerance as a result of a combination
      of severe chronotropic incompetence, limited stroke volume reserve caused by a
      reduced ventricular size and allograft diastolic dysfunction, and an abnormality
      in peripheral oxygen delivery or use. Efforts aimed at improving these factors
      may further enhance the functional capacity of these long-term survivors of heart
      transplantation.

PMID- 7727460
TI  - Association of pretransplantation antiheart antibodies with clinical course after
      heart transplantation.
AB  - METHODS: Sera from 129 patients awaiting heart transplantation were assayed for
      the presence of IgM and IgG antiheart antibodies by means of sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis and Western blotting. The patients'
      posttransplantation clinical course was assessed with regard to the amount of
      methylprednisolone, rabbit antithymocyte globulin, and OKT3 anti-T cell antibody,
      and the number of biopsy-confirmed rejection episodes. Before undergoing heart
      transplantation, approximately half the patients had weak IgM (45%) and weak IgG
      (48%) antiheart antibodies. However, 22.5% of the patients had strong IgM
      antiheart antibodies before transplantation, and they required more
      methylprednisolone than those who were negative and weak and approximately twice
      as much rabbit antithymocyte globulin as those who were negative, weak, or
      moderate. Six of the patients in this group required OKT3 therapy, and
      additionally they had a significantly greater number of rejection episodes than
      those patients who were negative (p = 0.006), or who had weak antiheart
      antibodies before transplantation (p = 0.001). RESULTS AND CONCLUSIONS: Analysis
      of the pattern of banding of strong IgM antiheart antibody sera showed antiheart
      antibodies most frequently against myocardial proteins of 35, 42, 50, 60, 70,
      110, 120, 150, 180, and 200 kDa. Several of these proteins were characterized by
      two-dimensional polyacrylamide gel electrophoresis and Western blotting as
      tropomyosin (35 kDa), actin (42 kDa), heat shock protein 60 (60 kDa), and heat
      shock protein 70 (70 kDa). All strong antiheart antibody sera showed reactivity
      against a 200 kDa protein corresponding to myosin heavy chain.

PMID- 7727461
TI  - Triple-drug immunosuppression with steroid discontinuation by six months after
      heart transplantation.
AB  - BACKGROUND: Triple-drug immunosuppression with cyclosporine, azathioprine, and
      prednisone is associated with complications which might be reduced by steroid
      withdrawal. METHODS: In two groups of heart transplant recipients maintained on
      an identical regimen of cyclosporine and azathioprine, prednisone was withdrawn
      in group I patients (n = 35) by 6 months after transplantation, whereas in group
      II patients (n = 49) prednisone was never discontinued. RESULTS: Survival was
      similar in the two groups. The incidence of acute graft rejection was
      significantly higher in group I (54%) than in group II (12%), whereas infective
      complications were significantly lower in group I than in group II (0.63 versus
      1.02 episode/patient). The degree of posttransplantation weight gain, lipid
      abnormalities, and incidence of hypertension were not modified by the fast
      tapering of prednisone, whereas the incidence of cataract and compression
      fracture and the degree of bone loss were significantly reduced in group I. Graft
      function and incidence of coronary artery disease were similar in the two groups.
      CONCLUSIONS: The present data suggest that prednisone can be safely withdrawn in
      heart transplant recipients without jeopardizing survival and graft function.
      Longer follow-up is needed to assess the full impact of early withdrawal of
      steroids from triple-drug immunosuppression, especially on long-term graft
      function and incidence of coronary artery disease. Benefits of early steroid
      withdrawal included a reduction in bone loss, which might ultimately have a major
      positive impact on the extent of long-term rehabilitation and exercise tolerance
      after heart transplantation.

PMID- 7727462
TI  - Efficacy of low-dose OKT3 as cytolytic induction therapy in heart
      transplantation.
AB  - BACKGROUND: The need for prophylactic cytolytic treatment in heart
      transplantation is a controversial issue. Its use, however, might prevent the
      onset of cellular rejection in the immediate postoperative period, facilitating
      patient management. It has recently been suggested that the administration of
      these products at low doses might have the same immunologic impact and would
      reduce secondary effects and the cost of treatment. METHODS: In a nonrandomized
      retrospective study, we assessed 45 consecutive patients who underwent orthotopic
      heart transplantation in 1992 and 1993. Six patients who died before receiving
      the complete OKT3 dose were excluded. Twenty-three patients were treated with
      5mg/day doses of OKT3 for 7 consecutive days. Another 16 patients received 2.5 mg
      of OKT3 for 7 consecutive days. RESULTS: There were no significant differences
      between the two groups with respect to CD3 counts on days 2 (0.1% +/- 0.3% versus
      0.04% +/- 0.25%; p > 0.05) and 6 (0.2% +/- 0.45% versus 0.1% +/- 0.3%; p > 0.05),
      number of rejection episodes (1.45% +/- 0.8% per year of follow-up versus 1.7% +/
      1.2%, p = 0.66), number of infectious complications (8 versus 3, p > 0.05),
      total methylprednisolone dose used to treat rejection crises (3900 +/- 2765
      versus 3600 +/- 1963 mg; p = 0.71), adverse effects attributed to OKT3 (two
      versus none), or length of the postoperative hospital stay (36.8 +/- 19 versus
      30.2 +/- 20.9 days). CONCLUSIONS: As cytolytic induction therapy in heart
      transplantation, a daily regimen of 2.5 mg of OKT3 for 7 days achieves the same
      clinical and immunologic effect as the conventional 5 mg/day dose. In addition,
      it results in a considerable reduction in the cost of treatment.

PMID- 7727463
TI  - Preventive treatment of coronary vasculopathy in heart transplantation by
      inhibition of smooth muscle cell proliferation with angiopeptin.
AB  - BACKGROUND: The underlying mechanism of accelerated coronary vasculopathy in
      cardiac allografts still remains unclear. Our hypothesis was that inhibition of
      smooth muscle cell proliferation with the somatostatine analogue Angiopeptin may
      reduce vasculopathy. METHODS: Fifty-four patients received Angiopeptin injections
      (1500 micrograms x three times daily subcutaneously) for 21 days after the
      operation and three additional injections with every rejection treatment.
      Angiography was performed yearly, and data were compared with a matched historic
      control group. RESULTS: Actuarial survival was 85% at 1 year and 80% at 2 years,
      comparable with our results in general (80%/77%). Forty-six long-term survivors
      could be followed by coronary angiography. At 1 year, vasculopathy was assessed
      in nine patients (17%). Of the 18 patients investigated at 2 years thus far, an
      additional three patients were found to have vasculopathy. In the control group
      vasculopathy was comparable, being 13% after 1 year and 20% after 2 years. A
      significantly lower incidence of rejections and lower creatinine values were
      found in the study group within the entire observation period (p < 0.05).
      CONCLUSIONS: We conclude that Angiopeptin treatment appears to be safe without
      significant side effects; it may reduce the number of acute rejections, at least
      during the first year after heart transplantation. However, the results of the 2
      year follow-up in the remaining patients would have to be included in assessing
      the effect of Angiopeptin. Long-term follow-up will be necessary to decide
      whether Angiopeptin will be helpful in reducing the incidence of transplant
      vasculopathy.

PMID- 7727464
TI  - Clinical-pathologic features of humoral rejection in cardiac allografts: a study
      in 81 consecutive patients.
AB  - BACKGROUND: Humoral rejection is an infrequently reported, poorly understood form
      of cardiac allograft rejection. METHODS: We reviewed 81 consecutive heart
      transplant recipients followed up to 3 years after transplantation to evaluate
      the frequency and significance of humoral rejection in this population.
      Histologic features evaluated included capillary endothelial cell swelling,
      interstitial edema and hemorrhage, and neutrophilic infiltration.
      Immunofluorescence studies with antibodies to immunoglobulin G, immunoglobulin A,
      immunoglobulin M, Clq, C'3, HLA-DR, and fibrinogen and immunoperoxidase staining
      for endothelial cells (factor VIII-related antigen) and macrophages (KP1 [CD68])
      were performed. Minimal criteria for the diagnosis of humoral rejection were
      capillary endothelial cell swelling and any immunoglobulin and complement
      staining in capillaries. Findings were graded and compared with concurrent
      hemodynamic measurements. RESULTS: Immunoperoxidase staining showed that most
      swollen cells in capillaries were macrophages and fewer were endothelial cells.
      Humoral rejection was detected in 102 biopsy specimens from 42 patients (52%),
      within 3 weeks of transplantation in 28, and 3 weeks to 4 months later in the
      other 14 patients. One patient had evidence of humoral rejection almost 3 years
      after transplantation. A third of biopsy specimens with humoral rejection were
      associated with abnormal hemodynamics; of these 33 specimens only five had
      significant (grade 3 or 4) coexisting cellular rejection. Histologic findings
      most often associated with hemodynamic abnormalities were diffuse capillary
      endothelial cell swelling and any interstitial hemorrhage or edema. Three
      patients died of humoral rejection; only 1 had coexisting cellular rejection
      (grade 3A). CONCLUSIONS: In our experience humoral rejection (1) is not uncommon
      (52% of patients), (2) is often (33% of cases) associated with hemodynamic
      abnormalities, and (3) may be fatal.

PMID- 7727465
TI  - Reliability and usefulness of immunofluorescence in heart transplantation.
AB  - BACKGROUND AND METHODS: To study the reliability and usefulness of
      immunofluorescence on heart biopsy specimens for routine monitoring of heart
      transplant recipients for rejection, frozen sections of 72 consecutive
      endomyocardial biopsy specimens from 18 heart transplant recipients during the
      first 6 weeks after transplantation (and later) and from 11 control specimens
      from donor hearts and other nontransplantation patients were studied. Fifteen
      patients received OKT3 induction. The diagnosis of vascular (humoral) rejection
      pattern as defined by Hammond was based on the microvascular deposition of
      immunoglobulin and C3 or C1q. Echocardiographic data and right-sided heart
      catheterization were obtained simultaneously. RESULTS: The results showed that
      immunofluorescence was positive for a vascular rejection pattern in 60% (43 of
      72) overall, in heart transplant recipients it was positive in 59% (36 of 61),
      and in control subjects it was positive in 63% (7 of 11). Most of the patients
      who had positive immunofluorescence had no hemodynamic compromise. Humoral
      rejection was not predicted by positive immunofluorescence in our study. We also
      found no correlation with either positive or negative immunofluorescence for the
      short-term or long-term outcome during the first 6 weeks after transplantation.
      CONCLUSION: The usefulness of routine immunofluorescence in all surveillance
      heart biopsies is questionable as determined by this study.

PMID- 7727466
TI  - Desaturated venous-to-arterial shunting reduces right-sided heart failure after
      cardiopulmonary bypass.
AB  - BACKGROUND: Right-sided circulatory failure is a major cause of morbidity in
      heart transplant and ventricular assist device recipients. METHODS: Several
      systems for managing right-sided circulatory failure with use of a right-to-left
      shunt without need for an oxygenator or systemic heparinization were designed and
      used clinically. RESULTS: A right-to-left shunt was successfully used to treat
      severe right-sided circulatory failure in both a transplant and a left
      ventricular assist device recipient. CONCLUSIONS: If constructed between the
      femoral vein and artery, such a shunt could (1) be easily inserted and removed,
      (2) selectively infuse the lower extremities with desaturated blood while
      maintaining cerebral and cardiac perfusion with saturated blood, (3) selectively
      reduce the risk of paradoxical emboli to the head and heart, and (4) provide a
      known and adjustable degree of shunting depending on the condition of the
      patient, a major advantage of this system compared with creation of an atrial
      septal defect.

PMID- 7727467
TI  - Load-independent analysis of a pulsatile right ventricular assist device.
AB  - BACKGROUND: Right ventricular assist devices are becoming increasingly used as
      both a bridge to heart transplantation and as a means of temporary support after
      cardiopulmonary bypass. There has also been a resurgence of interest in pulsatile
      devices fueled by anecdotal, clinical reports. However, a load-independent
      analysis of biventricular function after right ventricular assistance comparing a
      pulsatile versus a continuous-flow right ventricular assist device has not been
      performed, and we hypothesize that a pulsatile device is less detrimental to
      cardiac function than a conventional, nonpulsatile pump. METHODS: Sixteen dogs
      (20 to 25 kg) were instrumented through a median sternotomy for placement of left
      ventricular and right ventricular epicardial dimension transducers in the major,
      minor, and septal-free wall axes. Intracavitary micromanometers were placed in
      both ventricles as well. Baseline pressure-dimension data were collected, and the
      right atrium and pulmonary artery were cannulated. Right ventricular bypass with
      the use of a pneumatically driven pulsatile right ventricular assist device (SV =
      60 ml; n = 7) or a conventional continuous-flow centrifugal right ventricular
      assist device (n = 9) was instituted for a 4-hour duration. Animals were then
      weaned from right ventricular support and decannulated. After bypass,
      biventricular function data were then collected. The load-insensitive stroke work
      end diastolic volume relationship known as preload recruitable stroke work was
      derived and expressed as a fraction of baseline function along with conventional
      hemodynamic indexes, cardiac output, and pulmonary vascular resistance. RESULTS:
      Results of this analysis show no significant benefit to either right ventricular
      or left ventricular function (right ventricular preload recruitable stroke work
      index: 0.863 +/- 0.3 [pulsatile] versus 0.849 +/- 0.2 [continuous], left
      ventricular preload recruitable stroke work index: 0.880 +/- 0.4 [pulsatile]
      versus 0.821 +/- 0.3 [continuous] after pulsatile right ventricular support.
      Likewise, cardiac output (1.4 +/- 0.1 [pulsatile] versus 1.5 +/- 0.2 [continuous]
      L/min) and pulmonary vascular resistance (4.8 +/- 1.0 [pulsatile] versus 3.2 +/-
      1.1 [continuous] Wood Units) were not significantly different in either study
      group. CONCLUSIONS: We conclude from these data that pneumatically driven
      pulsatile right ventricular assist devices provide no additional benefit to
      myocardial performance beyond that of conventional, nonpulsatile pumps. Further
      studies investigating a speculative benefit from pulsatile circulatory support
      are necessary to further define a potential role for these novel devices.

PMID- 7727468
TI  - Use of a pulsatile right ventricular assist device and continuous arteriovenous
      hemodialysis in a 57-year-old man with a pulsatile left ventricular assist
      device.
AB  - BACKGROUND: Despite advances in the perioperative treatment of both heart
      transplant and left ventricular assist device recipients, right-sided circulatory
      failure refractory to medical management remains a major source of morbidity in
      the immediate postoperative period. In addition, hypervolemia is a frequent
      complication encountered in the treatment of these patients because of their
      large fluid intake requirements and relative potential for kidney failure.
      METHODS: Previous reports have documented the use of continuous-flow devices to
      support the failing right-sided circulation of patients after both left
      ventricular assist device insertion and orthotopic heart transplantation.
      However, such continuous-flow devices may carry the attendant risks of hemolysis
      and bleeding and may further require 24-hour monitoring by trained personnel. We
      report the temporary-use pulsatile Abiomed BVS 5000 right ventricular assist
      device and continuous arteriovenous hemodialysis in the recipient of a pulsatile
      TCI HeartMate 1000 IP left ventricular assist device both after left ventricular
      assist device implantation and after orthotopic heart transplantation. RESULTS:
      The patient was well at 13 months follow-up. CONCLUSIONS: The use of right
      ventricular assist devices and continuous arteriovenous hemodialysis in both
      transplant and left ventricular assist device recipients undoubtedly will remain
      important as the popularity of these two therapeutic modalities continues to
      grow.

PMID- 7727469
TI  - Heterotopic lung transplantation: temporary biologic support for reversible
      pulmonary insufficiency.
AB  - BACKGROUND: The mortality rate resulting from adult respiratory distress syndrome
      in patients awaiting orthotopic lung transplantation remains high. Providing an
      "extra" lung may provide a potential solution to support a failing pulmonary
      system. We hypothesized that using a heterotopic lung transplant can correct
      hypoxemia and hypercarbia in both the short term and the long term. METHODS:
      Seven mongrel dogs underwent transplantation of a left lung into the abdomen.
      Anastomosis between the left atrial cuff and the pulmonary artery of the donor
      lungs was accomplished to systemic venous and arterial circulations,
      respectively. The main stem bronchus was exteriorized, intubated, and ventilated.
      Immunosuppression consisted of prednisone and azathioprine both preoperatively
      and postoperatively. Progressive levels of systemic hypoxemia and hypercarbia
      were induced. The heterotopic lung transplant augmented oxygenation with a tidal
      volume of 300 cc, a fraction of inspired oxygen of 50%, and a respiratory rate of
      10 and then 20 breaths/min. Four animals were studied again at 48 hours. Flow
      through the heterotopic lung transplant ranged from 25% to 33% of the cardiac
      output. RESULTS: Statistically significant improvements were seen in both
      systemic oxygenation and ventilation in the short-term experiment. The systemic
      oxygen pressure improved from 37 +/- 3 mm Hg to 67 +/- 5 mm Hg after ventilation
      of the heterotopic lung transplant, and the carbon dioxide pressure improved from
      56 +/- 1 mm Hg to 43 +/- 2 mm Hg. At 48 hours an improvement in oxygen pressure
      was noted after ventilation of the heterotopic lung transplant, from 42 +/- 3 mm
      Hg to 56 +/- 2 mm Hg and an improvement in systemic carbon dioxide pressure was
      noted after ventilation of the heterotopic lung transplant from 57 +/- 7 mm Hg to
      46 +/- 4 mm Hg. CONCLUSIONS: The heterotopic lung transplant was able to provide
      effective gas exchange and support both oxygenation and ventilation after the
      induction of acute hypoxemia or hypercarbia, both immediately and at 48 hours
      after implantation. The heterotopic lung transplant may serve as an alternative
      mode of temporary support for those with acute respiratory insufficiency or as a
      bridge for those awaiting orthotopic lung transplantation.

PMID- 7727470
TI  - Tricuspid valve repair for tricuspid regurgitation after endomyocardial biopsy.

PMID- 7727471
TI  - Predictors of quality of life in patients with advanced heart failure awaiting
      transplantation.
AB  - BACKGROUND: Quality of life is an important outcome to measure in patients with
      end-stage heart disease who are awaiting heart transplantation. The purposes of
      this study were threefold: (1) to assess life satisfaction in multiple areas, (2)
      to examine correlations between life satisfaction and demographic, physiologic,
      and psychosocial variables, and (3) to identify predictors of quality of life in
      patients with advanced heart failure who were awaiting heart transplantation.
      METHODS: Data were collected from a convenience sample of 359 adult heart
      transplant candidates from a midwestern and a southern medical center. Eight
      instruments were used to gather data from patients. All tools had adequate
      psychometric support. Data were analyzed by using descriptive statistics, Pearson
      correlations, and stepwise multiple regression analysis. RESULTS: Results showed
      that patients were most satisfied with significant others (e.g., emotional
      support from others, children, and family's health) and least satisfied with
      their health and functioning (e.g., current health status, ability to travel, and
      energy for daily activities). Significant correlations were found between total
      life satisfaction and age, New York Heart Association Functional classification,
      total number of daily medications, functional disability, symptom distress,
      stress, coping, helpfulness of heart transplant team interventions, health
      perception, expectation of transplant success, and overall quality of life.
      CONCLUSIONS: Eleven of 19 variables were significant predictors of higher quality
      of life in patients with advanced heart failure awaiting heart transplantation
      and accounted for 49% of explained variance: less symptom distress, better health
      perception, greater helpfulness of heart transplant team interventions, less
      stress, better coping ability, less functional disability, less use of fatalistic
      coping, older age, greater effectiveness of optimistic coping, being unemployed,
      and the expectation of transplant success.

PMID- 7727472
TI  - Ability of antimyosin scintigraphy monitoring to exclude acute rejection during
      the first year after heart transplantation.
AB  - BACKGROUND: Antimyosin Fab fragment has been shown to bind to myosin leaked from
      necrotic cardiac cells but not to myosin in undamaged cells. The purpose of this
      investigation was to evaluate indium 111-antimyosin Fab fragment scintigraphy as
      a noninvasive technique in the diagnosis of acute rejection after heart
      transplantation. Simultaneous endomyocardial biopsy served as the gold standard.
      METHODS: Twenty-two patients had scintigraphic studies at weeks 3 to 4, 6, 10,
      26, and 52, but the next 16 patients underwent scintigraphy more often, that is,
      at all scheduled biopsies performed from week 3 to week 26 after transplantation.
      From analysis of the first 70 studies, an interstudy decrease in the patient's
      heart-to-lung ratio was classified as normal, that is, no rejection, whereas an
      unchanged or increased heart-to-lung ratio was considered pathologic. RESULTS: By
      use of this definition of negative and positive scintigraphic results,
      prospective analysis of 88 conclusive, consecutive studies showed 6 true- and 31
      false-positive studies (prevalence of rejection 8%), giving a low predictive
      value of a pathologic change in heart-to-lung ratio. Of the 51 studies with
      decreasing heart-to-lung ratio only 1 was a false negative, giving a predictive
      value of a negative study of 98% (95% confidence limits 90% to 100%).
      CONCLUSIONS: In conclusion, antimyosin scintigraphy is a promising noninvasive
      technique in the routine surveillance of acute heart rejection. Because of many
      false-positive results in the studies, biopsy should be used as a control for a
      pathologic heart-to-lung ratio.

PMID- 7727473
TI  - A double-blind placebo-controlled trial of low-dose ganciclovir to prevent
      cytomegalovirus disease after heart transplantation.
AB  - BACKGROUND: The aim of this double-blind, placebo-controlled study was to
      determine whether a prolonged course of low-dose ganciclovir prevented the
      development of clinical cytomegalovirus disease after heart transplantation.
      METHODS: Fifty-six consecutive patients were stratified into two groups:
      cytomegalovirus-positive recipients (n = 40) and cytomegalovirus-negative
      recipients of organs from cytomegalovirus-positive donors (n = 16). All patients
      received equine antithymocyte globulin induction for 7 days and maintenance doses
      of cyclosporine, azathioprine, and prednisolone. Ganciclovir (5 mg/kg
      intravenously) or matching placebo was given with the premedication, three times
      weekly for the first 6 weeks after transplantation and for another 2 weeks for
      each treated rejection episode between 6 and 12 weeks. RESULTS: Ganciclovir
      prophylaxis reduced the actuarial incidence of cytomegalovirus disease from 71%
      to 11% in cytomegalovirus-mismatched patients (p < 0.01). Ganciclovir prophylaxis
      did not reduce the incidence of cytomegalovirus disease in cytomegalovirus
      positive recipients (25% in both placebo and ganciclovir groups) but did delay
      its onset and reduce its morbidity. There were no adverse reactions during
      ganciclovir administration. Gastritis was the most common clinical manifestation
      of cytomegalovirus disease. Pneumonitis and myocarditis were seen only in placebo
      treated cytomegalovirus-mismatched patients. All patients with clinical
      cytomegalovirus disease responded to ganciclovir, 10 mg/kg/day for 2 weeks.
      CONCLUSIONS: Prolonged low-dose ganciclovir prophylaxis after heart
      transplantation reduces the incidence of cytomegalovirus disease in
      cytomegalovirus-mismatched patients and reduces the morbidity of cytomegalovirus
      disease in cytomegalovirus-positive recipients.

PMID- 7727474
TI  - Reduced work of breathing after single lung transplantation for emphysema.
AB  - BACKGROUND: Pulmonary emphysema, with or without chronic bronchitis, has emerged
      as the most common indication for successful single lung transplantation.
      Although gas exchange can be expected to improve after successful
      transplantation, such changes do not adequately explain the improvement in
      dyspnea experienced by these patients and resulting in improved quality of life.
      METHODS: We prospectively studied the respiratory mechanics of 14 single lung
      transplantation recipients with pulmonary emphysema, of whom 10 have been
      followed up beyond 1 year. The mean age of the group was 48.8 years (range, 42 to
      60 years) for the seven men and seven women. Average donor-predicted total lung
      capacity was 0.6 L (+0.2 [standard error]) greater than recipient-predicted total
      lung capacity. Comparison of pulmonary resistance, dynamic lung compliance, and
      static lung compliance were taken to examine the possible role of reduced airways
      resistance and of improved elastic recoil in the reduced work of breathing.
      Results were analyzed by means of a one-tailed paired Student t test and linear
      regression analysis (both stepwise and multivariate); results are tabulated by
      mean (+/- 1 [standard error]). RESULTS: Between preoperative measurements and 12
      months postoperatively, maximum lung elastic recoil increased from 8.1 (+/- 0.7)
      to 11.3 (+/- 1.0) cm H2O, p < 0.01; pulmonary resistance fell from 8.3 (+/- 0.8)
      to 5.4 (+/- 0.7) cm H2O sec/L, p < 0.01. Dynamic lung compliance fell from 0.23
      (+/- 0.04) to 0.12 (+/- 0.02) L/cm H2O, p < 0.02, and static lung compliance fell
      from 0.66 (+/- 0.13) to 0.22 (+/- 0.05) L/cm H2O, p < 0.001. CONCLUSIONS: The
      decline in lung compliance after single lung transplantation reflects the
      importance of improvement in elastic recoil and reduced chest wall distention,
      improving the work of breathing. The 67% decline in static lung compliance (300%
      increase in elastic recoil) is probably the single most important mechanical
      factor leading to reduced dyspnea after single lung transplantation for
      emphysema.

PMID- 7727475
TI  - Abdominal complications after lung transplantation.
AB  - BACKGROUND: Serious abdominal complications after heart and heart-lung
      transplantation have been a well-documented source of morbidity and mortality in
      this patient population. This report reviews the incidence and spectrum of
      abdominal complications occurring in lung transplant recipients at a single
      institution. METHOD: Between January 1988 and July 1993, 75 patients underwent
      lung transplantation (58 single lung, 16 bilateral single lung, and 1 double
      lung) at the University of Minnesota. RESULTS: Twelve patients (16%) sustained 20
      abdominal complications. There were 11 early abdominal complications (< or = 30
      days after transplantation) including prolonged adynamic ileus (4), diaphragmatic
      hernia after omental wrap (3), ischemic bowel (2), colitis with hemorrhage (1),
      and splenic injury after colonoscopy (1). There were nine late abdominal
      complications (range, 32 days to 28 months after transplantation) including
      colonic perforation (4), cholelithiasis/choledocholithiasis (2), development of a
      mesenteric pseudoaneurysm (1), fungal hepatic abscess (1), and intraabdominal
      hemorrhage (1). Twenty-six procedures were performed for management of the
      abdominal complications including: colonoscopy (7), colectomy (5), repair of
      diaphragmatic hernia (3), colostomy takedown (4), small-bowel resection (2), open
      cholecystectomy with common bile duct exploration (1), open cholecystectomy (1),
      splenectomy (1), mesenteric arterial pseudoaneurysm embolization (1), and
      percutaneous liver biopsy (1). Four patients died of causes attributable to their
      abdominal complications. CONCLUSIONS: In each case in which a death occurred,
      there was a delay between the onset of symptoms and diagnosis and intervention of
      more than 6 days. Abdominal complications accounted for 22% of all deaths in our
      lung transplantation group. A high index of suspicion and early recognition and
      intervention will decrease the morbidity and mortality caused by abdominal
      complications in lung transplant patients.

PMID- 7727476
TI  - Availability and selection of donors for pediatric heart transplantation.
AB  - METHODS: Applying generally accepted criteria for selection of adult heart
      donors, we conducted a retrospective study of brain-dead infants and children for
      assessment of suitability as donors for heart transplantation. Cardiac
      histopathologic studies were evaluated in all subjects undergoing autopsy.
      RESULTS: In 5 years there were 58 such patients, the majority of whom had head
      injury, near-drowning, near-miss sudden infant death syndrome, infection, or
      asphyxia. Of these, only five met the proposed clinical criteria. Most
      prospective donors were eliminated on the basis of prolonged cardiac arrest (n =
      33), pressor dependency (n = 25), and/or infection (n = 10). Forty-two subjects
      underwent autopsy, of whom 36 would not have been excluded as donors except on
      the basis of ischemic cardiac insult. Of these, 18 subjects were found to have
      essentially normal myocardium, nine had abnormal but potentially reversible
      microscopic changes, and nine had myocardial infarction. The pathologic findings
      were not predicted by the selection criteria, but severe chest trauma was not
      associated with infarction, eight of the nine patients with infarction had had
      cardiac arrest, and most of those with infarction had drowned or had had sudden
      infant death syndrome. CONCLUSIONS: The supply of donor organs for pediatric
      heart transplantation is very limited if selection criteria used for adult donors
      are applied. These criteria, however, do not correlate well with myocardial
      pathologic findings in infants and children. More accurate predictors of donor
      suitability are needed.

PMID- 7727477
TI  - Functional assessment and management of heart donors: a rationale for
      characterization and a guide to therapy.
AB  - BACKGROUND: Traditional methods for the functional evaluation of a donor heart
      have relied on superficial hemodynamic data and visual inspection of the action
      of the heart at sternotomy. The International Registry has continued to report
      significant mortality for heart transplant recipients from primary graft
      dysfunction that may be due to donor management, donor organ selection, organ
      preservation, or recipient factors. The literature reports the loss of at least
      25% of potential donors because of the provision of inadequate physiologic
      support. METHODS AND RESULTS: We have now spent several years in establishing and
      refining a strategy for optimizing donor management, which has resulted in the
      safe expansion of our donor pool by approximately 30%. Central to this management
      regimen has been the use of comprehensive perioperative invasive monitoring used
      by a cardiac anesthetist who takes responsibility for donor management during the
      retrieval operation. CONCLUSION: This article outlines the technique which has
      evolved for the functional evaluation of a donor heart, which is now used in our
      institution as a guide to management and as a basis for decision making regarding
      organ suitability.

PMID- 7727478
TI  - Use of the University of Wisconsin solution for the preservation of cell
      organelle activities in rat heart and lungs.
AB  - BACKGROUND: The University of Wisconsin storage solution has been successful in
      some model systems in extending the storage period of heart-lung grafts for
      transplantation. METHODS: In this study an aerated preparation of rat heart and
      lung was stored for 24 hours at 4 degrees C in either University of Wisconsin or
      St. Thomas' Hospital solution. Cell organelles (reticular, mitochondrial, and
      cell membrane fractions) were isolated from the stored hearts and lungs. Protein
      yield and enzyme activities were assayed for each cell organelle (reticular
      fractions: Ca(2+)-ATPase, NADPH-cytochrome C reductase; mitochondria: Ca(2+)
      ATPase, cytochrome C oxidase; cell membrane fraction: Na+,K(+)-ATPase, p
      nitrophenylphosphatase) as a measure of the recovery of function. RESULTS: Only
      the cell membrane fraction of heart and lung was not affected by storage in
      either St. Thomas' Hospital or University of Wisconsin solution with respect to
      protein yield (milligrams per gram of homogenate) or enzyme activities (nanomole
      per milligram per minute). The reticular fraction was the most sensitive to
      storage, with both protein yield and enzyme activities being significantly
      reduced in both the heart and the lung stored in University of Wisconsin of St.
      Thomas' Hospital solution (p < 0.05). CONCLUSION: The mitochondrial fraction was
      not preserved in lung in either St. Thomas' Hospital or University of Wisconsin
      solution but was preserved in the heart stored in St. Thomas' Hospital solution.
      These criteria provide preliminary screening for a superior solution that may
      then be used in more complicated transplantation models to more fully assess
      cardiac and pulmonary function.

PMID- 7727479
TI  - Distribution of lung preservation solutions in parenchyma and airways: influence
      of atelectasis and route of delivery.
AB  - BACKGROUND: Bronchial healing remains one of the dominant issues in lung
      transplantation. Among other factors the quality of airway protection during lung
      procurement may contribute to improve bronchial healing. METHODS: Thirty-three
      pigs were divided into four groups: controls (n = 6), those receiving antegrade
      delivery of Euro-Collins solution with (n = 4) and without prostacyclin (n = 9),
      and those receiving retrograde delivery of Euro-Collins solution (n = 14). In
      addition, the atelectatic and nonatelectatic regions of the lungs from all groups
      were compared. After preparation and cannulation, cardioplegic solution and Euro
      Collins solution for lung preservation were given simultaneously. After removal
      of the heart the double-lung bloc was harvested. During each experiment lungs
      were assessed by the following methods: dye-labeled microspheres for total and
      regional lung perfusion, tissue water content, pulmonary artery, left atrial and
      left ventricular pressures, cardiac output, lung temperature, and microscopic
      examination. Data were expressed as mean +/- standard error of the mean. RESULTS
      AND CONCLUSIONS: Our data show that (1) injection of modified dye-labeled
      microspheres is a useful method to determine absolute flow in lung parenchyma and
      airways, (2) determination of tissue water content is a simple and reproducible
      method to investigate the distribution of hyperosmolar lung preservation
      solutions, (3) atelectasis leads to a significant maldistribution of lung
      preservation solutions regardless of the route of delivery (0.7 +/- 0.2 versus
      6.5 +/- 1.0 ml/min/gm lung wet weight, p = 0.0001) and a severe increase in water
      content (80.6% +/- 0.4% versus 79.0% +/- 0.5%, p = 0.024), (4) prostacyclin added
      to the pulmonary artery flush solution results in only a slight improvement in
      the distribution, and (5) retrograde delivery of Euro-Collins solution through
      the left atrium is technically feasible and seems to improve flow to the airways
      even without the addition of prostacyclin.

PMID- 7727480
TI  - Effects of hyperkalemia on neonatal endothelium and smooth muscle.
AB  - BACKGROUND: Contradictory results have been reported regarding the effect of
      hyperkalemic cardioplegic or organ preservation solutions on endothelial and
      smooth muscle cells. The present study was designed to determine the effects of
      potassium concentrations and exposure times to hyperkalemia on endothelium
      derived relaxing factor (nitric oxide) biosynthesis and release, and smooth
      muscle function in neonatal vessels. METHODS: Aortic rings taken from neonatal
      rabbits were studied in organ baths at physiologic pressure. The effect of Krebs'
      solution containing 5, 25, 50, or 100 mmol/L potassium incubated for 45 minutes
      (group 1), St. Thomas' Hospital cardioplegic solution containing 16, 25, 50, or
      100 mmol/L potassium for 45 minutes (group 2), and Krebs' solution containing 5
      and 50 mmol/L potassium or St. Thomas' Hospital cardioplegic solution containing
      16 and 50 mmol/L potassium for 135 minutes (group 3) or 270 minutes (groups 4 and
      5) was examined. The rings were then washed and contracted with U46619 (30
      nmol/L). The ability to release endothelium-derived relaxing factor (nitric
      oxide) in response to acetylcholine was tested. RESULTS: The maximal relaxation
      induced by acetylcholine did not decrease in any group. Evidence of slight
      alteration of smooth muscle contraction was seen only in the rings incubated in
      Krebs' solution with 50 mmol/L potassium for 270 minutes (group 4) with unchanged
      maximal contraction and sensitivity to potassium (group 5). CONCLUSIONS: We
      conclude that after exposure for a limited time (4 1/2 hours), hyperkalemia per
      se does not significantly alter the function of endothelium to release
      endothelium-derived relaxing factor (nitric oxide) in response to acetylcholine
      and only slightly alters the contraction speed of smooth muscle in the neonatal
      rabbit aorta.

PMID- 7727481
TI  - Augmentation of oral tissues in rabbit using autogenous fat.
AB  - Patients with mild velopharyngeal incompetence (VPI) may have speech disorders,
      which are not sufficiently severe to warrant extensive surgical intervention, yet
      may not be amenable to correction by speech therapy alone. Augmentation of the
      posterior pharyngeal wall to aid in closure of the velopharyngeal sphincter may
      be beneficial in establishing better speech patterns, especially when combined
      with speech therapy. A variety of materials and techniques have been used in the
      past for this purpose. In this setting, autogenous fat may be transplanted
      without the risks incurred by augmentation with synthetic materials and involves
      very little donor site morbidity. The literature is somewhat contradictory,
      however, regarding the stability of the augmentation achieved using autogenous
      fat and there are no histologic studies describing the fate of fat injected into
      tissues of the oral cavity. Prior to introduction of this technique into clinical
      practice, this study was designed to investigate the fate of autogenous fat
      injected submucosally in the oropharyngeal region. Autogenous fat was injected
      into the anterior soft palate using the rabbit as a model. Histologic and gross
      inspections were performed at 2 days, 1, 2, and 4 weeks after injections. At the
      end of 4 weeks, at least 50% of the injection sites had visible evidence of
      augmentation, and 90% had histologic evidence of submucosal fat. In some
      instances most of the fat was resorbed; however, there were no instances of
      clinical infection or necrosis of the injection site. We conclude that submucosal
      injection of autogenous fat is a feasible alternative to using synthetic or other
      biologic materials for augmentation in the oral cavity.

PMID- 7727482
TI  - Effects of carbon monoxide and hypoxia on cleft lip in A/J mice.
AB  - Epidemiologic evidence indicates an increase in cleft lip with or without cleft
      palate [CL(P)] in infants of mothers who smoke cigarettes. It appears that the
      principle mechanism is through carbon monoxide (CO) decreasing the oxygen (O2)
      available to the embryo. Previous studies have shown that maternal respiratory
      hypoxia can increase the incidence of CL(P) in mice. The present investigation
      was designed to analyze the effects of altered levels of CO and O2 in respiratory
      gases on the incidence of CL(P) in genetically susceptible A/J mice. Results from
      blood gas analysis, after a 24-hour exposure of pregnant mice during the time of
      primary palate development, showed that CO levels of 180 ppm in air decrease
      oxyhemoglobin (%O2Hb) and increased carboxyhemoglobin (%COHb) to slightly above
      the high end of the range found in human studies of cigarette smokers.
      Interestingly, the control COHb levels were higher in our CL(P) sensitive mouse
      strain compared with those of the range of increases found in human smokers,
      versus nonsmoker studies, and that the increase for treated mice (3x) was at the
      low end of the range for smokers. Decreasing O2 levels to 10% from 21% (normal
      percentage in air) more severely decreased %O2Hb and moderately decreased %COHb.
      At 24 hours of exposure, the incidence of CL(P) and resorption was approximately
      the same for both the CO and the control groups, but there were significant
      increases in the incidence of resorptions in the hypoxia group and of CL(P) in
      relation to the CO group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727483
TI  - Cranio-orbito-zygomatic measurements from standard CT scans in unoperated
      Treacher Collins syndrome patients: comparison with normal controls.
AB  - Fourteen reproducible cranio-orbito-zygomatic measurements taken from 26 standard
      axial computed tomographic (CT) scans of unoperated individuals with symmetric
      forms of Treacher Collins syndrome (TCS) were compared to age-matched controls.
      The interorbital measurements of the TCS patients were at the mean when compared
      to their cohort group (medial and lateral orbital wall separation), while the
      zygomatic measurements were significantly less than normal confirming the extent
      of malar hypoplasia. The congenitally deficient lateral aspect of the orbits in
      TCS patients was confirmed by the greater than normal values measured for globe
      protrusion and medial orbital wall protrusion in conjunction with the diminished
      lateral orbital wall lengths, all of which use the lateral orbital rim as a
      reference point. The abnormal shape of the anterior cranial vault in patients
      with TCS was documented as a diminished intercoronal distance (width) and
      decreased cephalic length when compared to normal age-matched controls.

PMID- 7727484
TI  - Treatment of cleft palate associated with Robin sequence: appraisal of risk
      factors.
AB  - Mandibular hypoplasia, airway obstruction, and a typical wide U-shaped cleft
      palate comprise the Robin sequence. Although much has been written regarding the
      treatment of these patients in the neonatal period, the literature reveals little
      information regarding later care of the cleft palate in these patients. The
      purpose of this study is to examine patients with the Robin sequence and evaluate
      the risk of postsurgical problems and outcome related to the neonatal period.
      Thirty-six patients with the Robin sequence presenting from 1972 through 1990
      were reviewed. A majority of patients had feeding and respiratory difficulties,
      to varying degrees, following birth. These problems were treated successfully by
      maneuvers ranging from positioning to two infants who eventually required
      tracheostomy. Thirty-four patients had palate repair. Age at repair averaged 16.2
      months, and one third of patients had associated anomalies. Infants who
      experienced problems following palatoplasty were those who had histories of
      severe difficulties and complications in the early months of life. In addition,
      patients with associated congenital anomalies has significantly more problems at
      the time of palate repair than those without anomalies. Those patients with the
      Robin sequence, who historically had minimal difficulty following birth,
      experienced few complications at the time of palate repair. Of the 34 patients
      with repaired palates, 23 demonstrated sufficient follow-up to allow for
      evaluation of speech outcome. Satisfactory or normal speech production was noted
      in 65.4%. This is not significantly different from that observed in all patients
      undergoing cleft palate repair during this same time period (74.9%). Secondary
      pharyngoplasty procedures were required in 17.4%.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7727485
TI  - Hearing levels in Pierre Robin syndrome.
AB  - Hearing was tested in 18 patients with Pierre Robin syndrome (PRS). These results
      were compared with those obtained for 243 patients with either cleft lip or cleft
      palate, or both. None of the PRS group patients had middle ear or inner ear
      malformations, or sensorineural hearing loss in speech frequencies. Hearing loss
      in PRS is usually conductive, bilateral, and more frequent in PRS patients (30
      ears or 83.33%) than in patients who do not have PRS (290 ears or 59.67%). A
      significantly higher (p < .01) mean of hearing loss for air conduction in speech
      frequencies (MHLSF = 24.5 dB) was found in PRS patients than in patients without
      PRS (MHLSF = 17.8 dB). The ears of the PRS patients with hearing loss were
      examined, revealing middle ear effusion. In all cases, hearing was restored to a
      normal level through suction and the use of ventilation tubes.

PMID- 7727486
TI  - HONC measures in men and women: validity and variability.
AB  - Horii's (1980) Oral Nasal Coupling index (HONC) was used in measures of 20 women
      and 20 men with normal speech to validate procedures used for assessment of
      disordered nasal resonance. Subjects produced sustained vowels [i] and [a],
      repeated single word productions of "baby" and "mamie" and nonnasal and nasal
      sentences. Results showed that the correction factors generated during [m]
      calibration procedures differed significantly between women and men, but not over
      time within the single measurement session. Differences were also found for the
      decibel levels produced in the voice channel during the [m] calibration
      procedure: the women used higher dB levels, particularly towards the end of the
      session, than the men. In addition, dB levels differed over time. Differences of
      13 dB (HONC) were found to separate nonnasal from nasal sentences supporting the
      validity of the HONC measure. Smaller differences were found between sustained
      vowel and repeated single words and nasal sentences. Greater variability found
      for vowel productions also suggests that the sentence stimuli may be more
      effective for demonstrating hyper- or hyponasality.

PMID- 7727487
TI  - Acoustic rhinometric measurements of changes in velar positioning.
AB  - Acoustic rhinometry as a means to detect changes in velar position was examined
      in this study. Videofluoroscopic recordings were made of two normal speakers
      maintaining velopharyngeal open and velopharyngeal closed (silent /f/) targets.
      Simultaneous acoustic rhinometric recordings were made during the production of
      each stimulus. Determinations of changes in velar positioning during the closed
      samples were made from fluoroscopic recordings and compared to nasal cavity
      nasopharynx changes detected by rhinometry. The excellent agreement between the
      measures from the two procedures (less than 1 cm) indicates that acoustic
      rhinometry is capable of detecting changes in velar positioning during "silent"
      speech. Implications for assessment and future research are discussed.

PMID- 7727488
TI  - The role of maternal factors in the adaptation of children with craniofacial
      disfigurement.
AB  - This study hypothesized that maternal adjustment, perceptions, and social support
      would better predict child adaptation to craniofacial disfigurement than medical
      severity. Mothers of 77 children (ages 6-12) completed the Child Behavior
      Checklist, Beck Depression Inventory, Spielberger Trait Anxiety Scale, Social
      Support Questionnaire Revised, and Parenting Stress Index. Medical severity was
      assessed by the number of operations (craniofacial and other), comorbid medical
      conditions, and the Hay Attractiveness Scale. The children and mothers in our
      sample resembled a normal population in terms of their psychological functioning
      and quality of the mother-child relationships. Maternal adjustment and maternal
      perceptions of the mother-child relationship were more potent predictors of
      children's emotional adjustment than either medical severity or maternal social
      support.

PMID- 7727489
TI  - Pfeiffer syndrome: a clinical review.
AB  - The combination of bicoronal craniosynostosis, broad thumbs and great toes, and
      partial variable soft tissue syndactyly of the hands and feet (i.e., Pfeiffer
      syndrome) classically followed a benign clinical course. A review of the clinical
      features of those Pfeiffer syndrome patients presenting to our unit confirm
      another subgroup in whom the craniofacial and associated manifestations are more
      extreme, with a significant risk of early demise. The early aggressive surgical
      management of craniostenosis, hydrocephalus, exorbitism, faciostenosis, and upper
      airway obstruction has provided the potential for prolonged useful survival in
      these cases.

PMID- 7727490
TI  - Parent questionnaire for screening early language development in children with
      cleft palate.
AB  - This study investigated the efficacy of a parent questionnaire as a component for
      screening early language development of children 16 to 30 months of age with
      cleft lip and palate. Thirty nonsyndromic children with cleft lip and palate and
      30 children without clefts received the MacArthur Communicative Development
      Inventory: Toddler (CDI: Toddler), administered by a pediatrician. In addition, a
      speech-language screening was performed by a speech-language pathologist. Results
      of the two assessments indicated that the CDI:Toddler was a valid screener of
      language development when compared with a comprehensive speech-language
      screening. Language and speech characteristics of the subject populations are
      discussed. In particular, differences between the cleft and noncleft groups
      demonstrated evidence of delays in expressive language development in the
      children with cleft lip and palate.

PMID- 7727491
TI  - Planning mandibular distraction: preliminary report.
AB  - Normal lengths of the vertical ramus, body, and angle of the mandible at
      different ages are presented. Before mandibular distraction is embarked on, the
      extent of the deficiency of the mandible is assessed. The length of the vertical
      ramus and body are measured on cephalometric radiographs or three-dimensional
      computed tomography (3D CT) scans. Deficiency of the length of the mandible is
      calculated. The position of the pin placement angle (from the horizontal ramus)
      is calculated by means of the following formula: 180 degrees minus mandibular
      angle times vertical ramus deficiency divided by total deficiency. Placing the
      pins correctly will result in correction of the vertical ramus and body
      deficiency of the mandible and the excessively obtuse angle of the mandible will
      become more acute.

PMID- 7727492
TI  - Kabuki syndrome: underdiagnosed recognizable pattern in cleft palate patients.
AB  - Eight cases of Kabuki syndrome in non-Japanese patients are presented. (Although
      the name Kabuki Make-up syndrome has been used to identify this condition, the
      authors recommend that the term "make-up" be deleted from the designation as it
      has caused problems with some of the families.) Clinical features include a
      characteristic facies, developmental delay, musculoskeletal abnormalities, and
      dermatoglyphic differences. The phenotype appears to evolve over time making the
      diagnosis difficult in infancy. The progressive changes in the facial
      characteristics as well as the musculoskeletal problems suggest an underlying
      defect of the connective tissue. Finally, the syndrome appears to be more common
      in the non-Japanese population than previously appreciated, particularly in the
      cleft palate population.

PMID- 7727493
TI  - Comparison of tongue position during speech before and after pharyngeal flap
      surgery in hypernasal speakers.

PMID- 7727494
TI  - Fast reactions of cytochrome oxidase.

PMID- 7727495
TI  - A model of antimycin A binding based on structure-activity studies of synthetic
      antimycin A analogues.
AB  - The structural factors of antimycin A molecule required for inhibitory action
      were studied using newly synthesized antimycin A derivatives with bovine heart
      submitochondrial particles, in order to probe the interaction between antimycin A
      and its binding site. In particular, we focused upon the roles of the amide bond
      bridge, which connects the salicylic acid and dilactone ring moieties, and the 3
      formylamino group in the salicylic acid moiety. The lack of formation of an
      intramolecular hydrogen-bond between phenolic OH and amide carbonyl groups
      resulted in a remarkable loss of the activity (by four orders of magnitude),
      indicating that this hydrogen-bond is essential for the inhibition. This result
      suggested that both the phenolic OH and the carbonyl groups form a hydrogen-bond
      with some residues at a fixed conformation. In addition, the inhibitory potency
      was remarkably decreased by N-methylation of the amide bond moiety, indicating
      that the NH group might function in hydrogen-bond interaction with the binding
      site. The N-methylation of 3-formylamino group also resulted in a decrease in the
      activity, probably due to a loss of the rotational freedom of this functional
      group. Molecular orbital calculation studies with respect to the conformation of
      the 3-formylamino group indicated that this group takes an active conformation
      when the formyl carbonyl projects to the opposite side of the phenolic OH group.
      Based upon a series of structure-activity studies of synthetic antimycin A
      analogues, we propose a tentative model for antimycin A binding in its binding
      cavity.

PMID- 7727496
TI  - Primary structure and properties of the inhibitory protein of the mitochondrial
      ATPase (H(+)-ATP synthase) from potato.
AB  - The primary structure of the inhibitory protein (IF1) of the potato mitochondrial
      ATPase has been determined by protein sequencing, and its molecular weight
      determined by electrospray mass spectrometry. Both are consistent with a 56
      residue protein of molecular weight 6697. This protein shows only weak homology
      with IF1 sequences from mammals and yeasts, and significant deletions are present
      compared to these sequences. Homology is strongest in the region between residues
      22 and 46 (ox heart numbering), where 5 identities and 6 conserved residues are
      observed across all five IF1 species. In addition, this region shows homology
      with protein inhibitors from ATPases other than mitochondrial F1. It is suggested
      that this region might constitute an ATPase 'inhibitory motif'. Functional
      studies show that, unlike IF1 from mammals or yeasts, potato IF1 binds only
      poorly to ox heart F1, and does not show the ability to exist in 2 (alternate)
      stable conformations.

PMID- 7727497
TI  - Molecular structure of the 8.0 kDa subunit of cytochrome-c reductase from potato
      and its delta psi-dependent import into isolated mitochondria.
AB  - The cytochrome-c reductase (EC 1.10.2.2) of the mitochondrial respiratory chain
      couples electron transport from ubiquinol to cytochrome c with proton
      translocation across the inner mitochondrial membrane. The enzyme from potato was
      shown to be composed of 10 subunits. Isolation and characterization of cDNA
      clones for the second smallest subunit reveal an open reading frame of 216 bp
      encoding a protein of 8.0 kDa. The protein exhibits similarities to a 7.2/7.3 kDa
      subunit of cytochrome-c reductase from bovine and yeast, that is localized on the
      intermembrane space side of the enzyme complex. It also shows similarity to a
      previously unidentified 7.8 kDa protein of cytochrome-c reductase from Euglena.
      The potato 8.0 kDa protein has a segmental structure, as its sequence can be
      divided into four parts, each comprising a central Arg-(Xaa)5-Val motif. N
      terminal sequencing of the mature 8.0 kDa proteins indicates the absence of a
      cleavable mitochondrial targeting sequence. Import of the in vitro synthesized
      8.0 kDa protein into isolated potato mitochondria confirms the lack of a
      presequence and reveals a dependence of the transport on the membrane potential
      delta psi across the inner mitochondrial membrane. These features are unique
      among the intermembrane space proteins known so far.

PMID- 7727498
TI  - Mitochondrial bioenergetics is affected by the herbicide paraquat.
AB  - The potential toxicity of the herbicide paraquat (1,1-dimethyl-4,4'-bipyridylium
      dichloride) was tested in bioenergetic functions of isolated rat liver
      mitochondria. Paraquat increases the rate of State 4 respiration, doubling at 10
      mM, indicating uncoupling effects. Additionally, State 3 respiration is depressed
      by about 15%, at 10 mM paraquat, whereas uncoupled respiration in the presence of
      CCCP is depressed by about 30%. Furthermore, paraquat partially inhibits the
      ATPase activity through a direct effect on this enzyme complex. However, at high
      concentrations (5-10 mM), the ATPase activity is stimulated, probably as
      consequence of the described uncoupling effect. Depression of respiratory
      activity is mediated through partial inhibitions of mitochondrial complexes III
      and IV. Paraquat depresses delta psi as a function of herbicide concentration. In
      addition, the depolarization induced by ADP is decreased and repolarization is
      biphasic suggesting a double effect. Repolarization resumes at a level
      consistently higher than the initial level before ADP addition, for paraquat
      concentrations up to 10 mM. This particular effect is clear at 1 mM paraquat and
      tends to fade out with increasing concentrations of the herbicide.

PMID- 7727499
TI  - F1-ATPase alpha-subunit made up from two fragments (1-395, 396-503) is stabilized
      by ATP and complexes containing it obey altered kinetics.
AB  - Inferred from the crystal structure of mitochondrial F1-ATPase (Abrahams, J.P. et
      al. (1994) Nature 370, 621-628), the proteinase-sensitive region around Phe-395
      of thermophilic F1-ATPase alpha-subunit corresponds to the loop which connects
      main part of the carboxyl-terminal helical bundle domain with the ATP binding
      domain. This loop is in contact with the gamma- and adjacent beta-subunits. Two
      polypeptides corresponding to the sequence 1-395 and 396-503 of the alpha-subunit
      were expressed in Escherichia coli cells and they were copurified as an
      apparently functional alpha-subunit (alpha(395/396)) made up of two polypeptides.
      The isolated alpha(395/396) was stabilized by ATP-Mg, but not by ADP-Mg, although
      it bound both ATP-Mg and ADP-Mg with similar affinities (Kd, 11 microM and 14
      microM, respectively). The alpha(395/396) was reconstitutable into
      alpha(395/396)3 beta 3 and alpha(395/396)3 beta 3 gamma complexes. Different from
      the intact the ATP-Mg-induced dissociation into alpha 1 beta 1 heterodimers. ATP
      hydrolysis by the alpha(395/396)3 beta 3 gamma complex underwent a slow initial
      phase, whereas the intact alpha 3 beta 3 gamma complex exhibited an accelerated
      initial phase. Steady-state ATPase activity at various ATP concentrations showed
      negative cooperativity for the intact alpha 3 beta 3 gamma complex but apparently
      positive cooperativity for the alpha(395/396)3 beta 3 gamma complex. The ATPase
      activities at a saturating ATP concentration of the complexes containing the
      alpha(395/396) were 180% of those containing intact alpha-subunits. These results
      indicate that a loop around Phe-395 is involved in intersubunit interaction in F1
      ATPase.

PMID- 7727500
TI  - Functional expression of the ENA1(PMR2)-ATPase of Saccharomyces cerevisiae in
      Schizosaccharomyces pombe.
AB  - Na+ efflux and Na+ tolerance depend on a putative P-type ATPase encoded by the
      gene ENA1(PMR2) in Saccharomyces cerevisiae and on a putative Na+/H+ antiporter
      encoded by the gene sod2 in Schizosaccharomyces pombe. This report shows that a
      sod2::ura4 mutant of S. pombe transformed with the ENA1 gene of S. cerevisiae
      expressed the ENA1 protein, and recovered Na+ efflux and Na+ tolerance. The
      efflux of Na+ in the wild strain of S. pombe was sensitive to the transmembrane
      Na+ and H+ gradients, whereas in the sod2::ura4 mutant transformed with ENA1 it
      was independent of these gradients. The data give further support to the notion
      that ENA1 and sod2 encode Na+ transporters and not regulators of the process of
      Na+ export; they show also the physiological consequences of exporting Na+
      through an Na(+)-ATPase or an Na+/H+ antiporter.

PMID- 7727501
TI  - Is monoamine oxidase activity in the outer mitochondrial membrane influenced by
      the mitochondrial respiratory state?
AB  - Monoamine oxidase activity was measured in isolated rat liver mitochondria using
      the radiochemical assay with [14C]tyramine as substrate. With toluene as the
      extracting solvent the apparent activity in the resting state (State 4) was much
      higher than in the active state (State 3) in agreement with Smith and Reid
      (Smith, G.S. and Reid, R.A. (1978) Biochem. J. 176, 1011-1014). However, with
      ethyl acetate or diethyl ether as extracting solvents, the activity in both
      states was almost identical and several times higher than that measured with
      toluene. p-Hydroxyphenylacetaldehyde, p-hydroxyphenylacetalcohol and p
      hydroxyphenylacetic acid were identified as final reaction products, the latter
      one being hardly extractable with toluene. It is concluded that monoamine oxidase
      activity is not influenced by the respiratory state of mitochondria and that
      differences found by Smith and Reid are due to different extractability of
      secondary reaction products. NADPH-dependent aldehyde reductase was tentatively
      identified in rat liver mitochondria, its specific activity amounting to about
      one fourth of that in the cytosol.

PMID- 7727502
TI  - Identification of glandular kallikrein in dog pancreas and determination of its
      tissue distribution.
AB  - In order to establish a formal link between previously purified canine urinary
      kallikrein and dog pancreatic kallikrein whose cDNA sequence has recently been
      published, we have isolated the pancreatic kallikrein from that animal species.
      Pancreatic cytosol proteins were sequentially subjected to chromatography on DEAE
      Sepharose CL-6B and Concanavalin A-Sepharose, to an autolysis step and finally to
      two-dimensional gel electrophoresis. Kallikrein immunoreactive spots were
      identified with an antibody directed against canine urinary kallikrein. These
      proteins were isolated after electroblotting and the amino acid sequence of their
      NH2-terminal portion was determined by microsequencing. The sequence was found to
      be identical to the one deduced from pancreatic kallikrein cDNA. Using the same
      antibody and immunohistochemical procedures, kallikrein was found to be present
      in the pancreas, the salivary glands, the kidney, the colon, the lungs and the
      testis. These results thus confirm the molecular nature of a glandular kallikrein
      in the canine species.

PMID- 7727503
TI  - Difference between cancer cells and the corresponding normal tissue in view of
      stereoselective hydrolysis of synthetic esters.
AB  - This study has aimed at taking information necessary for design of anticancer
      prodrugs modified with chiral acyl group, especially about the effect of
      chirality of the acyl group on its enzymic removal in specific cells. Thus, 13
      species of chiral esters were synthesized and stereoselectivity in their enzymic
      hydrolysis was investigated with six cancer cell lines, solid tumors, and the
      corresponding normal tissues. Cultured cancer cells from rat liver, pancreas, and
      muscle hydrolyzed the R enantiomer of (+/-)-ethyl 2-methoxy-2-phenylacetate (3c)
      more preferentially than its antipode, whereas this stereoselectivity was
      reversed in the reaction by homogenate of the corresponding normal tissue of rat.
      The difference in stereoselectivity between cancer cells and normal tissue was
      also found in the hydrolysis of other esters including those of actual anticancer
      agents, p-hydroxyaniline mustard and 5-fluorouridine. The investigation was
      expanded to real tumor to show that the degree of stereoselectivity or the
      hydrolytic activity was significantly different between a human brain tumor and
      its surrounding normal tissue for such substrates as (+/-)-ethyl 2
      phenoxypropanoate and N-trifluoroacetylphenylalaninate. The esterases of rat
      liver cancer cells (Anr4) and normal rat liver gave different band patterns in
      active staining after gel electrophoresis. The enzymes were fractionated by ion
      exchange column chromatography and then tested on their stereoselectivity against
      (+/-)-3c. Comparison of the results and electrophoretograms of the fractions
      suggests that esterases with different stereoselectivity are expressed in
      different ways by normal and cancer cells. These results show that
      stereoselectivity in enzymic hydrolysis of some synthetic chiral esters is
      different between cancer and normal cells, leading to the possibility that
      specific activation of ester-type anticancer prodrugs in cancer cells would be
      controlled by the chiral structure of the acyl group.

PMID- 7727504
TI  - Amino acid sequence of TsTX-V, an alpha-toxin from Tityus serrulatus scorpion
      venom, and its effect on K+ permeability of beta-cells from isolated rat islets
      of Langerhans.
AB  - Highly purified Tityustoxin V (TsTX-V), an alpha-toxin isolated from the venom of
      the Brazilian scorpion Tityus serrulatus, was obtained by ion exchange
      chromatography on carboxymethylcellulose-52. It was shown to be homogeneous by
      reverse phase high performance liquid chromatography, N-terminal sequencing
      (first 39 residues) of the reduced and alkylated protein and by polyacrylamide
      gel electrophoresis in the presence of sodium dodecylsulfate and tricine.
      Following enzymatic digestion, the complete amino acid sequence (64 residues) was
      determined. The sequence showed higher homology with the toxins from the venoms
      of the North African than with those of the North and South American scorpions.
      Using the rate of 86Rb+ release from depolarized rat pancreatic beta-cells as a
      measure of K+ permeability changes, TsTX-V (5.6 micrograms/ml) was found to
      increase by 2.0-2.4-fold the rate of marker outflow in the presence of 8.3 mM
      glucose. This effect was persistent and slowly reversible, showing similarity to
      that induced by 100 microM veratridine, an agent that increases the open period
      of Na+ channels, delaying their inactivation. It is suggested that, by extending
      the depolarized period, TsTX-V indirectly affects beta-cell voltage-dependent K+
      channels, thus increasing K+ permeability.

PMID- 7727505
TI  - Purification and characterization of an alkaline amylopullulanase with both alpha
      1,4 and alpha-1,6 hydrolytic activity from alkalophilic Bacillus sp. KSM-1378.
AB  - The novel alkaline amylopullulanase produced by alkalophilic Bacillus sp. KSM
      1378 was purified to an electrophoretically homogeneous state from culture
      medium. The purified enzyme was a glycoprotein with an apparent molecular mass of
      about 210 kDa and an isoelectric point of pH 4.8. The N-terminal amino acid
      sequence was Glu-Thr-Gly-Asp-Lys-Arg-Ile-Glu-Phe-Ser-Tyr-Glu-Arg-Pro and showed
      no homology to the N-terminal regions of other amylopullulanases reported to
      date. The enzyme was able to attack specifically the alpha-1,6 linkages in
      pullulan to generate maltotriose as the major end product, as well as the alpha
      1,4 linkages in amylose, amylopectin and glycogen to generate various
      oligosaccharides. The pH and temperature optima for the pullulanase and alpha
      amylase activities were pH 9.5 and 50 degrees C and pH 8.5 and 50 degrees C
      respectively. Both activities were strongly inhibited by well characterized
      inhibitors, such as diethyl pyrocarbonate and N-bromosuccinimide. The pullulanase
      activity was specifically inactivated by Hg2+ ions, alpha-cyclodextrin and beta
      cyclodextrin while the amylase activity was strongly inhibited by EDTA and EGTA,
      although inhibition could be reversed by Ca2+ ions. It is suggested that the
      single alkaline amylopullulanase protein has two different active sites, one for
      the cleavage of alpha-1,4-linked substrates and one for the cleavage of alpha-1,6
      linked substrates.

PMID- 7727506
TI  - Characteristic induction of hepatic metallothionein in mice by tumor
      transplantation.
AB  - Based on the previous finding that hepatic metallothionein (MT) level was tumor
      growth dependently elevated in tumor-transplanted mice, the mode of induction of
      hepatic MT in tumor-bearing mice was comparatively studied with inflammation
      induced and stress-subjected mice. The prefeeding with zinc (Zn)-deficient diet
      for 1 wk suppressed both the growth of tumor and the increase of hepatic MT and
      Zn in tumor-bearing mice. The postfeeding with Zn-deficient diet also suppressed
      hepatic MT induction in the course of tumor growth. On the other hand, in the
      other two experimental model mice, the prefeeding with Zn-deficient diet did not
      suppress the increase of hepatic MT and Zn. Further, the dexamethasone treatment
      stimulated hepatic MT induction in tumor-bearing mice, but rather reduced that in
      inflammation-induced mice. These results suggest that hepatic MT was induced
      uniquely in tumor-bearing mice and that Zn may play a key role for the induction
      of hepatic MT by tumor transplantation.

PMID- 7727507
TI  - Long-term maintenance of functional rat hepatocytes in primary culture by
      additions of pyruvate and various hormones.
AB  - Mature adult rat hepatocytes were cultured as monolayers in serum-free Williams
      medium E containing 10(-7) M each of insulin (Ins), dexamethasone (Dex) and
      triiodothyronine (T3) and 30 mM pyruvate. The hepatocytes remained
      morphologically intact for at least 14 days, during which period they maintained
      normal liver functions such as the expressions of cytochrome P-450 mRNA and
      glucokinase and secretion of albumin. They also retained the ability to resume
      proliferation. Cells cultured with pyruvate had a much higher ATP level than
      those without pyruvate, suggesting that pyruvate can sustain functional
      hepatocytes for a long period in culture in the presence of Ins, Dex and T3,
      probably by producing enough energy for their maintenance.

PMID- 7727508
TI  - Regulation of glutamine and glucose metabolism by cell volume in lymphocytes and
      macrophages.
AB  - The effects of osmotically and sucrose-induced cell volume changes on glutamine
      and glucose metabolism were investigated in rat lymphocytes and macrophages
      incubated for 10-60 min at 37 degrees C in Krebs-Henseleit bicarbonate buffer (pH
      7.4). Decreasing extracellular osmolarity from 336 to 286 mOsmol by decreasing
      medium NaCl from 119 to 94 mM increased cell volume and the rates of glutamine
      metabolism and glycolysis in both cell types. Conversely, increasing
      extracellular osmolarity from 286 to 386 mOsmol by the addition of 50 and 100 mM
      D-mannitol progressively decreased both cell volume and the rates of glutamine
      and glucose metabolism in lymphocytes and macrophages. At the same medium
      osmolarity of 336 mOsmol, the rates of glutamine metabolism and glycolysis were
      greater with the addition of 50 mM sucrose than with that of 25 mM NaCl. The
      sucrose-induced increase in cell volume, which is due to the uptake of sucrose by
      lymphocytes and macrophages via pinocytosis, is associated with enhanced rates of
      glutamine metabolism and glycolysis. Our findings suggest that cell volume change
      may be a hitherto unrecognized mechanism for regulating metabolism in lymphocytes
      and macrophages. The enhanced glutamine and glucose metabolism in these cells in
      response to mitogenic stimulation or immunological activation may result, at
      least in part, from the concomitant increase in cell volume.

PMID- 7727509
TI  - Purification, characterization and localization of mitochondrial dihydroorotate
      dehydrogenase in Plasmodium falciparum, human malaria parasite.
AB  - The mitochondrial dihydroorotate dehydrogenase (DHODase), the single redox
      reaction in the pyrimidine de novo synthetic pathway, was purified to near
      homogeneity by detergent solubilization and fast protein liquid chromatography
      (FPLC) techniques from the mature trophozoites and schizonts of Plasmodium
      falciparum, human malaria parasite. The purified DHODase was monofunctional
      protein with a M(r) of 56,000 +/- 4000, based on Superose 12 gel filtration FPLC
      and SDS-PAGE analyses. Polyclonal antibodies raised against the purified P.
      falciparum protein was cross-reacted with P. berghei, rodent malaria parasite.
      The optimal activity of DHODase required long chain of coenzyme Q (CoQ6-10) which
      were essential for electron transfer. The Km and kcat values for L-dihydroorotate
      were 14.4 +/- 5.9 microM and 15.0 +/- 1.4 min-1, respectively; for CoQ6, they
      were 22.5 +/- 6.4 microM and 21.6 +/- 3.4 min-1. L-Orotate, an enzymatic product,
      was a strong competitive inhibitor with Ki of 18.2 +/- 3.6 microM. The 5
      substituted L-orotates having antimalarial activities against P. falciparum in
      vitro were found to be competitive inhibitors. The inhibitory effect by these 5
      substituted L-orotates on the malarial DHODase was different from the mammalian
      enzyme. Various benzoquinones and naphthoquinones were found to inhibit the
      purified DHODase activity at a different degree. Mitochondria from erythrocytic
      cycle of P. falciparum were purified, using differential centrifugation and
      followed by Percoll density gradient separation, with purifications of 13-fold
      and overall yields of 33%. The double-membraned mitochondria had a few tubular
      like cristae structure as what found in many protozoan parasites. DHODase was
      localized inside the mitochondria as probed by immunogold labeling with the
      polyclonal antibodies and selective solubilization by digitonin.

PMID- 7727510
TI  - Mitochondrial sites of hydrogen peroxide production in reperfused rat kidney
      cortex.
AB  - Electron transport and production of O2-/H2O2 by the NADH dehydrogenase flavin
      semiquinone (FMNH.) and ubisemiquinone (UQH.) were studied in a model of in vivo
      ischemia-reperfusion in rat kidney. H2O2 production rates were assessed in
      isolated mitochondria using either succinate, with and without antimycin, or
      malate-glutamate, with and without rotenone. Respiratory activities of isolated
      mitochondria and activity of NADH- and succinate-cytochrome c reductase and of
      NADH- and succinate-dehydrogenase in submitochondrial particles were measured to
      evaluate the electron flux throughout respiratory carriers. The mitochondrial
      H2O2 production rate was approximately 1.5- and 4-times increased in ischemic and
      ischemic-reperfused kidneys, respectively. Ischemia caused a marked decrease in
      the electron transport throughout the NADH-UQ segment with no significant changes
      either in the NADH dehydrogenase activity or in the electron flux trough the
      succinate-cytochrome oxidase segment. Reperfusion did not further affect the NADH
      ubiquinone segment but markedly inhibited the succinate-supported oxygen
      consumption, succinate-cytochrome c reductase and succinate dehydrogenase
      activity. Our results show a redistribution of the electron flux with an
      increased rate of superoxide anion/hydrogen peroxide production at NADH
      dehydrogenase in mitochondria subjected to ischemia only. After 10 min
      reperfusion an impairment of the electron flow at succinate-cytochrome c segment
      is established and hydrogen peroxide production by UQH. increases up to maximal
      values becoming the major source of superoxide anion/hydrogen peroxide.

PMID- 7727511
TI  - Effects of creatine and beta-guanidinopropionic acid on the growth of Ehrlich
      ascites tumor cells: i.p. injection and culture study.
AB  - Growth of Ehrlich ascites tumor (EAT) cells in the abdominal space of mice or in
      cell culture was studied in response to i.p. injection or addition, respectively,
      of creatine or creatine analogue beta-guanidinopropionic acid (beta-GPA). The
      increase in body weight of the mice due to cancer growth was less in the beta-GPA
      injected than in the creatine- or sham-injected group. The volume of abdominal
      ascites and total cell counts at 11th day after implantation of EAT cells was
      significantly less in the beta-GPA than in the other groups. The proliferation
      rate of EAT cells in the beta-GPA group was 27% and 35% of the creatine- and sham
      injected groups, respectively. Supplementation of creatine tended to enhance the
      growth of EAT cells. The creatine concentration in ascites fluid was
      approximately 4-times greater than in blood plasma of sham-injected control mice.
      But the creatine content in EAT cells was significantly reduced to approximately
      50% in response to beta-GPA injection. Cell culture without creatine caused a
      significant decrease in viability. The viability was improved, however, by
      addition of either creatine or serum into the medium. By contrast, it was not
      significantly increased by addition of serum alone which caused only a minor
      elevation of the creatine level (23 microM). It is suggested that EAT cell growth
      is inhibited by lowering the availability of creatine in association with some
      unknown factors in serum or ascites fluid.

PMID- 7727512
TI  - Modulation by iron loading and chelation of the uptake of non-transferrin-bound
      iron by human liver cells.
AB  - Hepatic non-transferrin-bound Fe (NTBI) flux and its regulation were
      characterized by measuring the uptake of Fe from [59Fe]/nitrilotriacetate (NTA)
      complexes in control and Fe-loaded cultures of human hepatocellular carcinoma
      cells (HepG2). Exposure to ferric ammonium citrate (FAC) for 1 to 7 days resulted
      in a time- and dose-dependent increase in the rate of NTBI uptake. In contrast to
      previous studies showing a dependence of the rate of Fe uptake on extracellular
      Fe, this was positively correlated with total cellular Fe content. The Fe3+
      chelating agents deferoxamine (DFO), 1,2-dimethyl-3-hydroxypyrid-4-one (CP 020)
      and 1,2-diethyl-3-hydroxypyrid-4-one (CP 094) prevented or diminished the
      increase in NTBI transport when present during Fe loading and reversed the
      stimulation in pre-loaded cells in relation to their abilities to decrease
      intracellular iron. Although saturation of the Fe uptake process was not achieved
      in control cells, kinetic modelling to include linear diffusion-controlled
      processes yielded estimated parameters of Km = 4.3 microM and Vmax = 2.6
      fmol/micrograms protein/min for the underlying process. There was a significant
      increase in the apparent Vmax (31.2 fmol/micrograms protein per min) for NTBI
      uptake in Fe-loaded cells, suggesting that Fe loading increases the number of a
      rate-limiting carrier site for Fe. Km also increased to 15.2 microM, comparable
      to values reported when whole liver is perfused with FeSO4. We conclude that
      HepG2 cells possess a transferrin-independent mechanism of Fe accumulation that
      responds reversibly to a regulatory intracellular Fe pool.

PMID- 7727513
TI  - A study of binary complexes of Escherichia coli maltodextrin phosphorylase: alpha
      D-glucose 1-methylenephosphonate as a probe of pyridoxal 5'-phosphate-substrate
      interactions.
AB  - The glucose 1-phosphate (Glc-1-P) analog alpha-D-glucose 1-methylenephosphonate
      (Glc-1-MeP) inhibits competitively Escherichia coli maltodextrin phosphorylases
      against Glc-1-P (Ki = 0.20 mM) but also Pi (Ki = 0.36 mM). Exchange of the active
      site residue Glu637 to Asp by site-directed mutagenesis abolishes inhibition only
      in the synthesis direction (S-mode), while the degradative direction (P-mode) was
      not affected. Structural and conformational differences of the S-mode versus P
      mode were also revealed by 31P-NMR spectroscopy by comparing chemical shifts of
      the cofactor pyridoxal-P in binary complexes formed either in the presence of Glc
      1-MeP or of arsenate. In contrast the apparent pK of pyridoxal-P in both binary
      complexes was closely similar. Again, the total chemical shift of pyridoxal-P in
      the synthesis mode respectively degradative mode was differently affected in the
      binary complexes of the Glu637Asp mutant enzyme. This supports the contention
      that differential binding of the substrates in the synthesis or the degradative
      mode changes the arrangement and mutual interactions of cofactor phosphate and
      substrate phosphates.

PMID- 7727514
TI  - Enhanced tropoelastin-degrading activity during cell passages in cultured smooth
      muscle cells.
AB  - Tropoelastin expression in vascular smooth muscle cells during serial cell
      passages from the primary to the tertiary culture was studied. The level of
      tropoelastin was found to be greatly reduced as the number of cell passages
      increased. The translational activity and level of elastin mRNA were essentially
      unchanged throughout the cell passages. The reduction in tropoelastin expression
      was not due to the repetitive trypsin treatment nor to the prolyl hydroxylation
      level of the newly-synthesized elastin. A comparable decline in tropoelastin
      expression was also found with increasing cell division in the primary cultures
      plated at different cell densities. A pulse-chase experiment revealed that the
      newly-synthesized elastin in the tertiary culture degraded more rapidly than that
      in the primary culture. The culture medium harvested from the tertiary culture
      exhibited a higher tropoelastin-degrading activity than that from the primary
      culture in the test-tube. The degrading activity of the tertiary culture was
      inhibited by the addition of 1 mM ethylenediaminetetraacetic acid or 1 mM
      phenylmethylsulfonyl fluoride, but not by 1 mM N-ethylmaleimide. These results
      suggest that the reduction in tropoelastin expression during the cell passages
      from the primary to the tertiary culture is due to the enhanced tropoelastin
      degrading activity of the tertiary culture. The transition to tropoelastin
      degrading phenotype during cell passages may explain the biological mechanisms of
      smooth muscle cell migration from the media to the intima observed in the
      pathological conditions.

PMID- 7727515
TI  - Cytotoxic effects of ricin without an interchain disulfide bond: genetic
      modification and chemical crosslinking studies.
AB  - Ricin is a toxic glycoprotein made of two polypeptide chains (A and B) linked by
      a disulfide bond. Ricin binds to cells by the B chain and is then internalized.
      The interchain disulfide bond is believed to be reduced in endosomes, and the A
      chain is then subsequently translocated to cytoplasm where it inactivates
      ribosomes. To understand the role of the disulfide bond in ricin toxicity, we
      prepared two types of ricin molecules. First, cysteine 259 of the A chain was
      mutated to an alanine residue. The mutant A chain was then reassociated with the
      native B chain to determine whether ricin is biologically active in the absence
      of an interchain disulfide bond. Reassociated mutant ricin showed a 40-fold
      reduction in biological activity. Binding studies using a hydrophobic
      fluorescence probe indicated that the associated complex was stable only at
      neutral pH and became highly unstable at a lower pH characteristic of the
      endosomal milieu. In the second construct, the interchain disulfide bond was
      replaced with a non-reducible bond by chemical derivatization. Interestingly, the
      non-reducible ricin molecule was equally cytotoxic as native ricin. These results
      show: (i) that the interchain disulfide bond is necessary to hold the A chain and
      the B chain together at endosomal pH, and (ii) that intact ricin may be
      transported to the cytoplasm where proteolysis or hydrolysis may occur to release
      the biologically active moiety.

PMID- 7727516
TI  - Activation of alkylhydrazines to free radical intermediates by ethanol-inducible
      cytochrome P-4502E1 (CYP2E1).
AB  - Electron spin resonance (EPR) spectroscopy analysis using the spin trapping agent
      4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) was used to measure the formation of
      free radical intermediates during NADPH-dependent oxidation of 1-methyl-, 1-ethyl
      , and 1-isopropylhydrazine in rat liver microsomes and in reconstituted enzyme
      systems. The experiments in microsomes revealed that the specific activation of
      the hydrazines, as measured by the EPR signal intensities, was about two-fold
      higher, when expressed per nmol of P-450, in microsomes from rats treated with
      ethanol (EtOH) as compared to membranes isolated from either phenobarbital (PB)-,
      beta-naphthoflavone (beta-NF)-treated or control rats. Furthermore, kinetic
      experiments revealed that EtOH-microsomes had an apparent affinity for 1
      ethylhydrazine about one order of magnitude higher than PB-microsomes. In
      reconstituted vesicular systems composed of phospholipids, NADPH cytochrome P-450
      reductase and P-450, the intensities of EPR signals produced by the formation of
      the methyl-, ethyl- and isopropyl-free radicals, were 3- to 5-fold more intense
      in membrane vesicles containing ethanol-inducible CYP2E1 than phenobarbital
      inducible CYP2B1. By contrast, CYP1A2, CYP2B4 and CYP2C4 were inefficient
      catalysts of radical formation. Desferrioxamine, catalase and superoxide
      dismutase did not influence the extent of ethyl radicals formed in EtOH
      microsomes, indicating that hydroxyl radicals are not involved in the CYP2E1
      dependent activation of 1-ethylhydrazine. Addition of cytochrome b5, an efficient
      donor of the second electron to P-450 and hence an inhibitor of the formation of
      the oxy-cytochrome P-450 complex, increased to be consistent with the results,
      did not influence the amount of ethyl radicals trapped. In liver microsomes from
      untreated rats selective substrates of CYP2E1, such as diethyl-dithiocarbamate
      and p-nitrophenol, as well as anti-CYP2E1-IgG, inhibited the free radical
      formation from 1-ethylhydrazine by about 60%. The anti-CYP2E1 IgG used
      significantly inhibited ethyl radical production also in human liver microsomes
      incubated with 1-ethylhydrazine and 4-POBN. Taken together, these results
      indicate that CYP2E1, as compared to other rat liver cytochromes P-450, is an
      efficient catalyst of transformation of alkylhydrazines to free radical
      intermediates, a finding that might be of importance in the development of the
      toxicity of these compounds.

PMID- 7727517
TI  - Effect of detergents and endogenous lipids on the activity and properties of
      tyrosinase and its related proteins.
AB  - Within mammalian melanocytes, melanin biosynthesis is controlled by three enzymes
      structurally related: tyrosinase and two tyrosinase related proteins, TRP1 and
      TRP2. These melanosomal enzymes are integral membrane proteins with a carboxyl
      tail oriented to the cytoplasm, a single membrane-spanning helix and the bulk of
      the protein located inside the melanosome. Their solubilization is usually
      carried out by treatment of melanosomal preparations with non-ionic detergents,
      but, so far, no comparative study of the effect of the detergents employed on the
      properties of the solubilized proteins has been reported. We have compared the
      effect of the detergents Brij-35, Nonidet P-40, Tween-20, sodium deoxycholate and
      Triton X-114 on several properties of the melanogenic enzymes, including the
      solubilization yield, stability, electrophoretic behaviour and accessibility of
      epitopes located in the carboxyl tail to specific antibodies. Our data indicate
      that not only the total amount of enzymes solubilized, but also their relative
      proportions in the solubilized preparations depend on the detergent used. The non
      ionic detergents apparently interact strongly with the melanogenic enzymes,
      affecting their mobility in SDS-PAGE, and might induce different conformations of
      the carboxyl tail. Complete replacement of lipids by the detergents results in a
      decreased stability that can be partially reversed by the addition of endogenous
      lipids. This treatment also produces a noticeable activation of the tyrosinase
      isoenzymes, which is higher for TRP1 than for tyrosinase. Taken together, these
      data show that the transmembrane and carboxyl fragments of the proteins of the
      tyrosinase family might modulate the stability and activity of the melanogenic
      enzymes.

PMID- 7727518
TI  - Identification of essential lysyl and cysteinyl residues, and the amino acid
      sequence at the substrate-binding site of retinal oxidase.
AB  - Retinal oxidase, which synthesizes all-trans and 9-cis retinoic acid from all
      trans and 9-cis-retinal, has been purified from rabbit liver cytosol. The
      substrate-binding site of the retinal oxidase was investigated with some chemical
      modification reagents. Lysyl-specific pyridoxal 5'-phosphate (PLP) and cysteinyl
      specific p-chloromercuribenzoate (PCMB) competitively inhibited the activity of
      the retinal oxidase, and the inhibition could be prevented by the presence of all
      trans-retinal or its derivatives. Treatment with sodium borohydride (NaBH4)
      resulted in covalent attachment of PLP to the lysyl residue of the retinal
      oxidase and the PLP modified-retinal oxidase was cut with cyanogen bromide, and
      the polypeptides modified with PLP were further digested with trypsin. Two of the
      peptides modified with PLP were purified from the digested polypeptide mixture
      and their amino acid sequences were determined.

PMID- 7727519
TI  - Expression and subcellular distribution of phosphoenolpyruvate carboxykinase in
      primary cultures of rabbit kidney proximal tubule cells: comparative study with
      renal and hepatic PEPCK in vivo.
AB  - The behaviour of the phosphoenolpyruvate carboxykinase (PEPCK) in rabbit proximal
      tubule cells in primary culture was investigated and compared with renal and
      hepatic PEPCK in vivo. The enzyme activity decreased rapidly in rabbit proximal
      tubule cells developed in hormonally defined medium supplemented with glucose and
      insulin. In this condition, the cytosolic form disappears with time. Without
      glucose and insulin, the subcellular location of PEPCK is similar to the location
      observed in proximal tubule freshly isolated and in renal cortex, with approx.
      50% of mitochondrial form and approx. 50% of cytosolic form. However, the levels
      of mRNA that encode the cytosolic PEPCK are not detectable in cell cultures,
      whatever the medium composition. Treatment with dibutyryl cAMP caused a 14-fold
      induction of PEPCK mRNA in 6 h. This result indicates that the transcription of
      cytosolic PEPCK can be induced in cell cultures. Lactate or pyruvate additions
      did not modify the levels of PEPCK mRNA whereas specific activity increased
      rapidly, suggesting an activation of an inactive form in cell cultures. Moreover,
      lactate induced increased specific activity of the sole mitochondrial form while
      pyruvate induced increased specific activities of both mitochondrial and
      cytosolic form. Thus, subcellular location of PEPCK in rabbit proximal tubule
      cells appears to be modulated by the available substrate in culture medium. This
      observation parallels the changes observed in vivo since a modification of
      subcellular location of this enzyme was seen between fed and fasted rabbit, when
      subcellular distribution remains similar between fed and starved rats. Moreover,
      in the fasted liver of rabbit, a decrease of the mitochondrial PEPCK specific
      activity is seen concomitant with an increase in cytosolic PEPCK activity. These
      results point out the relative contributions of the cytosolic and mitochondrial
      PEPCK to rabbit gluconeogenesis.

PMID- 7727520
TI  - K rev-1 protein is abundantly expressed in the rat spinal cord.
AB  - The K rev-1 gene, which was originally identified as a dominantly functioning
      tumor suppressor gene inducing a flat revertant of a v-K-ras-transformed NIH 3T3
      cell line, was abundantly expressed in the mammalian brain [Kitayama et al.
      (1989) Cell 56, 77-84]. To investigate where K rev-1 and its family ras proteins
      are distributed in the central nervous system, we isolated the membrane fractions
      from several regions of the brain and spinal cord of rats by subcellular
      fractionation and analyzed those proteins by immunoblot analysis with the
      specific monoclonal antibodies, K rev-1 protein was detected at the highest level
      in the spinal cord among areas of the central nervous system which included
      cerebral cortex, cerebellum, hippocampus, and olfactory bulb. On the other hand,
      ras proteins were found at similar levels in these regions. Within the spinal
      cord, K rev-1 and ras proteins were detected at a comparable level in the ventral
      and dorsal parts, while they were much less in the dorsal root ganglion than in
      the spinal cord. They showed the differential expression during early postnatal
      development: K rev-1 protein increased and ras proteins were at relatively high
      levels. When K rev-1 and ras proteins were examined in synaptosomes from the
      lumbar spinal cord of newborn rats, most of them were detected not in the
      synaptic vesicles but in the synaptic plasma membranes. K rev-1 protein as well
      as ras proteins might be involved in neuronal functions in the spinal cord such
      as sensory processing and motor control.

PMID- 7727521
TI  - Characteristics and regulation of 11 beta-hydroxysteroid dehydrogenase of
      proximal and distal nephron.
AB  - Enzymatic properties of the enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD),
      which confers mineralocorticoid selectivity, have been explored in the
      aldosterone-sensitive collecting duct (CCD) and the aldosterone-insensitive Pars
      Recta (PR) of the rat kidney. After incubation of freshly isolated tubular
      segments with [3H]corticosterone (3H-B) or [3H]dehydrocorticosterone (3H-A), the
      rate of transformation of 3H-B into 3H-A (dehydrogenase activity), or the reverse
      reaction (reductase activity) were measured by HPLC, Vmax for dehydrogenase
      activity was found to be 8- to 10-fold higher in CCD than PR. The enzyme
      functions over a very wide range (0.1-5000 nM) of corticosterone concentration.
      In CCD, enzyme kinetics suggest either the presence of two 11-HSD forms,
      differing by their affinity for corticosterone, or complex kinetics. Addition of
      NAD or NADP to permeabilized tubules revealed that dehydrogenase activity is NAD
      dependent in CCD and NADP-dependent in PR. Cofactor addition was ineffective in
      intact tubules. CCD exhibited an exclusive dehydrogenase activity, whereas in PR
      dehydrogenase and reductase activity were found. No regulation of dehydrogenase
      activity could be evidenced in adrenalectomized rats receiving or not
      aldosterone, corticosterone or dexamethasone, for 2 h, 3 days or 4 days. We
      conclude that 11-HSD in the CCD and PR differs by its Vmax and cofactor
      dependence. Corticosteroid hormones do not influence 11-HSD activity.

PMID- 7727522
TI  - Polymorphism in the glutathione conjugation activity of human erythrocytes
      towards ethylene dibromide and 1,2-epoxy-3-(p-nitrophenoxy)-propane.
AB  - In this study a polymorphism in the conjugating activity of human erythrocyte
      cytosol towards the dihaloethane, ethylene dibromide (EDB; 1,2-dibromoethane) was
      found. Two out of 12 human erythrocyte cytosols did not catalyze the formation of
      glutathione (GSH) conjugates of [1,2-14C]EDB. Ten cytosols formed the S,S'
      ethylenebis(GSH) conjugate at a rate ranging from 0.5 to 3.2 (mean 1.76 +/- 0.95)
      pmol min-1 (mg protein)-1. The activity of the cytosols towards EDB was compared
      with the activity towards 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP) and 1
      chloro-2,4-dinitrobenzene (CDNB). The GSH conjugates formed from EDB, EPNP and
      CDNB were all quantified by HPLC. Every cytosol was active with the classical GST
      substrate CDNB (2.04 +/- 0.74 nmol min-1 (mg protein)-1). The two samples not
      showing any detectable activity towards EDB were also inactive towards EPNP: The
      activity towards EDB correlated significantly with EPNP (rs = 0.90, P < 0.005;
      Spearman's rank correlation), but not with CDNB (rs = 0.36, P > 0.10). In the
      incubations with EPNP, the alpha-, mu-, and pi- class glutathione S-transferase
      (GST) inhibitor S-hexyl(GSH) was included, indicating that the class-theta GST is
      the principal GST class conjugating EDB in erythrocyte cytosol. The apparent
      polymorphism of GST-theta which has recently been recognized to be crucial for
      several mono- and dihalomethanes, will thus also have considerable implications
      for the risk assessment of EDB.

PMID- 7727523
TI  - Isolation and characterization of a flocculating protein from Moringa oleifera
      Lam.
AB  - A flocculating protein from the seeds of Moringa oleifera Lam. was isolated by
      extraction with phosphate buffer followed by cation exchange chromatography. The
      molecular mass of the protein determined by SDS-PAGE was about 6.5 kDa, the
      isoelectric point was above pH 10. Amino acid analysis and sequencing showed high
      contents of glutamine, arginine and proline, and a total of 60 residues. The
      amino terminus is blocked by pyroglutamate. The flocculant capacity, determined
      in glass powder suspension, is comparable to that of a cationic polymer on
      polyacrylamide basis. Flocculation activity may be explained by the patch charge
      mechanism due to low molecular weight and high charge density.

PMID- 7727524
TI  - Beta-N-acetylhexosaminidases A and S have similar sub-cellular distributions in
      HL-60 cells.
AB  - In HL-60 cells the most abundant isoenzymes of beta-N-acetyl-hexosaminidase are A
      (alpha beta) and S (alpha alpha). Sub-cellular fractionation of HL-60 cells by
      differential centrifugation showed that both A and S forms were present in the
      lysosomal and post-lysosomal (soluble) fractions in approximately equal
      abundance. Ion-exchange chromatography showed that a fraction enriched with
      plasma membranes had the A form, and a form of beta-N-acetylhexosaminidase less
      acidic than A, but there was no S. Analysis of the alpha-subunits of beta-N
      acetylhexosaminidases A and S using Western blotting and immuno-detection with
      antisera raised to synthetic peptides showed that mature alpha-subunits were
      present in both A and S isolated from the lysosomal fraction. This observation
      establishes that the alpha alpha-dimer of beta-N-acetyl-hexosaminidase (S) can be
      transported to lysosomes in HL-60 cells whereas there is good evidence that this
      does not take place in fibroblasts. HL-60 cells were not stimulated to secrete
      lysosomal enzymes by incubating them with NH4Cl and, unlike fibroblasts, are
      unlikely to use mannose-6-phosphate mediated transport of beta-N
      acetylhexosaminidases to lysosomes. Comparison of the sequence of the beta-N
      acetylhexosaminidase alpha-subunit with a 43 amino acid sequence of cathepsin D,
      though to function in the mannose-6-phosphate independent targeting of this
      enzyme to lysosomes, showed alignment in a region towards the C-terminus in which
      21% of the residues were identical with the interposition of a one amino acid
      gap.

PMID- 7727525
TI  - Direct measurement of the accumulation and mitochondrial conversion of nitric
      oxide within Chinese hamster ovary cells using an intracellular electron
      paramagnetic resonance technique.
AB  - We have developed an electron paramagnetic resonance (EPR) method for the
      nondestructive detection and quantification of intracellular NO in real time.
      Based upon this technique, we have obtained evidence for the metabolism of this
      bioregulatory molecule by mitochondria. Line-broadening of the EPR signal of a
      coal derivative, fusinite, was calibrated as a function of NO concentration in
      aqueous solution. The methodology was validated using two compounds which release
      NO in a controlled and predictable manner with first-order rate constants k1 =
      5.0 x 0.10(-3) s-1 and k'1 = 3.4 x 10(-4) s-1 (35 degrees C). Fusinite was
      internalized in Chinese hamster ovary cells (CHO) by phagocytosis, after which
      the cells were allowed to consume the available O2, producing an hypoxic
      environment. The NO released from one of the NO donors, added to the culture
      fluid at an initial concentration of 50 microM, was directly measured in the
      intracellular environment as line-broadening of the fusinite EPR signal. The
      linewidth diminished with time, indicating that NO was being converted to a non
      paramagnetic species by the cells with an apparent zero-order rate constant of 5
      x 10(8) NO molecules cell-1 min-1 (20 degrees C). Addition of cyanide to the
      culture medium (5 mM final concentration) inhibited this disappearance of NO. NO
      also was converted in the presence of isolated mitochondria in the absence of
      oxygen. These observations suggest that under hypoxic conditions, there exists in
      CHO cells a metabolic pathway for the conversion of NO to diamagnetic species,
      which involves interactions with mitochondria.

PMID- 7727526
TI  - Kinetic studies on the removal of extracellular tert-butyl hydroperoxide by
      cultured fibroblasts.
AB  - In fibroblasts toxic hydroperoxides are removed mainly by GSH peroxidase. The
      reaction depends on NADPH, since GSSG must be reduced by GSSG reductase for
      recycling. In this work we have studied the kinetics of tert-butyl hydroperoxide
      (tBH) removal by cultured fibroblasts in relation to the GSSG reduction. The rate
      of the reaction showed biphasic dependence on tBH concentration. About a third of
      the reaction was saturated below 10 microM tBH, while the rest of the reaction
      showed less steep dependence, reaching a plateau at 200 microM tBH. The latter
      reaction is thought to be due to GSH peroxidase, and the concentration dependence
      could be explained on the basis of reaction kinetics of GSH peroxidase and GSSG
      reductase. The maximum rate of tBH removal was estimated as 40-50 nmol tBH/min/mg
      of protein, while the glutathione reductase activity is the solubilized cell was
      33.0 +/- 3.5 nmol GSSG/min/mg of protein. It was concluded that, under the
      oxidative stress as in the present experiments, the step catalyzed by GSSG
      reductase is rate-limiting in the reaction sequence.

PMID- 7727527
TI  - Properties of hemagglutinins newly separated from toxic phytoplankton.
AB  - Unique substances of the hemagglutinating activity were separated from unialgal
      cultures of the toxic phytoflagellates, Chattonella marina and Gymnodinium sp.
      Molecular masses of the substances were estimated to be 14,000 in Chattonella and
      15,000 in Gymnodinium. These two substances contained phosphorus, hexose
      (galactose) and glycerol in the following molar ratios; 1.00:1.18:1.24
      (Chattonella) and 1.00:1.07:1.10 (Gymnodinium). Hemagglutinating titres using
      rabbit red blood cells were inferred to be 25,000 in both preparations. In the
      presence of Chattonella hemagglutinin (0.10-0.50 microM), the growth of C. marina
      in Provasoli's ES media was little affected during 24 h of incubation, whereas a
      marked suppression took place in growth in Gymnodinium sp. (50% inhibition, 0.12
      microM) or the diatom Nitzschia closterium (0.17 microM). On the other hand,
      Gymnodinium hemagglutinin inhibited the growth of the three species of
      phytoplankton. A 50% inhibition occurred at 0.12 microM in C. marina, at 0.22
      microM in N. closterium or at 0.50 microM in Gymnodinium sp.

PMID- 7727528
TI  - Changes in [Ca2+]i in cultured rat proximal tubular epithelium: an in vitro model
      for renal ischemia.
AB  - Two components of ischemia, oxygen deprivation and glycolytic inhibition, were
      studied in primary cultures of rat proximal tubular epithelial cells (PTE).
      Changes in cytosolic Ca2+ ([Ca2+]i) and its relationship to loss of mitochondrial
      membrane potential (delta psi m) and cell killing were characterized in single
      cells whereas ATP and LDH release were determined in populations of monolayer
      PTE. (1) Inhibition of mitochondrial respiration with KCN or anoxia resulted in
      little decrease in ATP or cell killing and slight change in [Ca2+]i over many
      hours. (2) Inhibition of respiration and glycolysis with anoxic HBSS minus
      glucose resulted in decreased ATP (54.4%) and cell killing (20%) during 5 h
      anoxic exposure. In all cases, but at highly variable times (113 +/- 62 min),
      [Ca2+]i initially rose to > 1 microM. In some cases it immediately dropped,
      stabilizing at about 500 nM for up to 1 h and rising again just prior to cell
      death. (3) Inhibition with anoxia + 1 mM IAA resulted in rapid depletion of ATP
      and cell killing, with increases in [Ca2+]i to > 1 microM by 20 +/- 2 min. (4)
      Depletion of glycolytic metabolites by depriving cells of substrate for 12 h (in
      HBSS minus glucose) before subjecting to anoxia minus glucose resulted in
      increases in [Ca2+]i at 40 +/- 17 min followed by cell killing. (5) Injury with
      anoxic HBSS minus glucose was reversed by reaeration before or during the initial
      rise in [Ca2+]i. Later reaeration resulted in rapid cell killing. In all cases,
      delta psi m was dissipated only after [Ca2+]i was significantly elevated.

PMID- 7727529
TI  - Effects of surface modification of materials on human neutrophil activation.
AB  - The properties of a polymer surface affect the cellular functions and morphology
      of cells in contact with the polymer. In this paper, we will demonstrate the
      effects of surface modification of materials on various neutrophil markers of
      activation. The sulfonation of a polystyrene surface caused increases in its
      negative charge and hydrophilicity. The sulfonation did not affect the number of
      adhered neutrophils, but the shape of the neutrophils adhered on the material was
      different; a round shape on highly sulfonated polystyrene and a spread shape on
      weakly sulfonated or non-sulfonated polystyrene. Expression of the adhesion
      molecule, CD11b, on neutrophils was also affected by the properties of the
      polymer surface. CD11b was expressed in neutrophils adhered on polystyrene and
      the expression decreased with increasing sulfonation of the surface. The
      expression of CD11b on the neutrophils on highly sulfonated polystyrene was the
      same as that on non-adhered neutrophils. In contrast, the expression of CD11a was
      not affected by the properties of the material surface. The F-actin content of
      activated neutrophils and the production of active oxygen groups detected by
      means of luminol-dependent chemiluminescence were also dependent on the sulfo
      group content of the material surface. Finally, the translocation of protein
      kinase C (PKC) was determined in neutrophils adhered to these materials. Compared
      to non-adhered cells, the ratio of membrane bound to cytosolic PKC increased in
      adhered cells, but the increase was suppressed by sulfonation of the material
      surface. These data suggest that activation of neutrophils on polystyrene is
      suppressed by surface modification with increasing negative charge and/or
      hydrophilicity.

PMID- 7727530
TI  - Amine oxidases from Aspergillus niger: identification of a novel flavin-dependent
      enzyme.
AB  - Upon induction with various amine sources, two different amine oxidases are
      expressed in the filamentous fungus Aspergillus niger. The enzymes which can be
      separated by anion exchange chromatography exhibit a similar substrate
      specificity pattern. From cofactor and inhibitor analysis it was found that one
      amine oxidase is identical to the earlier reported copper-containing amine
      oxidase (Yamada, H., Adachi, O. and Ogata, K. (1965) Agric. Biol. Chem. 29, 912
      917) with 6-hydroxydopa (TOPA) quinone as the active site cofactor. The second
      form is a hitherto unknown flavoprotein of 55 kDa, which shows many of the
      characteristic properties of the mammalian monoamine oxidases (MAO). From
      substrate specificity and inhibitor susceptibility, it is suggested that the
      monoamine oxidase from A. niger (MAO-N) is a prototype of the two mammalian
      enzymes, MAO-A and MAO-B. A partial cDNA clone which encodes an amino-terminal
      peptide of 53 amino acid residues was identified by lambda gt11 immunoscreening.
      The consensus sequence of the putative flavin adenine dinucleotide (FAD) binding
      site is found within this sequence.

PMID- 7727531
TI  - Increased heparin binding by site directed mutagenesis of a recombinant chimera
      of bombyxin and insulin-like growth factor II.
AB  - BOMIGF, a chimera between bombyxin and insulin-like growth factor II (IGF II) has
      been modified and extended to a total of 85 amino acids including 7 additional
      basic amino acids. The new peptide bound heparin as efficiently as GM-CSF and
      much better than IGF II or BOMIGF. It could be retained on albumin-coated tissue
      culture wells without loosing its capacity to stimulate thymidine incorporation
      into erythroid cells of fetal bovine liver and on fibronectin-heparin coated
      wells keeping its mitogenic activity towards L6 muscle cells.

PMID- 7727532
TI  - Consequences of altered aspartate aminotransferase activity on 13C-glutamate
      labelling by the tricarboxylic acid cycle in intact rat hearts.
AB  - The appearance of 13C label in glutamate has been used to quantify cellular
      tricarboxylic acid (TCA) cycle activity using 13C-NMR spectroscopy. Glutamate is
      linked to the TCA cycle by the amino-transferase reactions, however the
      consequences of alterations in amino-transferase activity on glutamate labelling
      kinetics, at a constant total tricarboxylic acid cycle activity, have not been
      investigated. Aspartate amino-transferase activity in [2-13C]acetate-perfused
      beating rat hearts was found to be similar to total TCA cycle flux in the
      presence of normal perfusion conditions and was reduced by more than 50% with the
      subsequent administration of amino-oxyacetic acid (AOA). AOA did not reduce
      contractile or kinetic measures of total TCA cycle flux, but did slow the 13C
      labelling of glutamate, in accord with current mathematical predictions. The
      impact of similar reductions in amino-transferase activity on estimates of total
      TCA cycle flux derived from several previously reported methods was also
      evaluated. Because total TCA cycle and the amino-transferase activities both
      affect the kinetics of 13C-glutamate labelling and because the amino-transferase
      activities are often unknown under physiologic conditions and can be reduced
      under pathologic conditions, the calculation of total TCA cycle flux from 13C-NMR
      data in the future is probably best accomplished either with a sufficiently
      sophisticated mathematical model that assesses amino-transferase activity or with
      an empiric model that is relatively insensitive to variations in amino
      transferase activity.

PMID- 7727533
TI  - Identification of SPT14/CWH6 as the yeast homologue of hPIG-A, a gene involved in
      the biosynthesis of GPI anchors.
AB  - Cwh6 is a temperature-sensitive cell wall mutant of Saccharomyces cerevisiae.
      CWH6 was found to be identical to SPT14, a gene that is highly homologous to both
      human PIG-A and to RFAK from Salmonella typhimurium. PIG-A and RFAK are involved
      in transferring N-acetylglucosamine to, respectively, a GPI anchor precursor and
      to lipopolysaccharides. Because cell walls of cwh6 are greatly reduced in
      mannose, and because some cell wall proteins are known to be incorporated into
      the cell wall through a GPI-anchor dependent mechanism, we propose that
      Spt14p/Cwh6p is involved in transferring N-acetylglucosamine to a precursor of
      GPI anchors. We further propose that the majority of cell wall proteins are
      incorporated into the cell wall through a GPI anchor.

PMID- 7727534
TI  - Cloning and sequencing of beta-mannanase gene from Bacillus subtilis NM-39.
AB  - A gene encoding beta-mannanase from Bacillus subtilis NM-39 was cloned into
      Escherichia coli DH5 alpha by using pUC 18 and its nucleotide sequence was
      determined. The beta-mannanase gene was 1080 base pairs long and encoded a mature
      protein of 336 amino acids and a signal peptide of 24 amino acids. The deduced
      amino acid sequence of the cloned mannanase showed sequence homology with
      mannanase from alkalophilic Bacillus sp. strain AM-001 (about 50%).

PMID- 7727535
TI  - Lysosomal storage diseases.

PMID- 7727536
TI  - Anticholinesterasic drugs: tacrine but not physostigmine, accumulates in acidic
      compartments of the cells.
AB  - Tacrine (THA) and physostigmine (PHS) have been used in Alzheimer's disease
      therapy for their anticholinesterasic activity. Here we show that THA is taken up
      in rat lysosomes in an energy-dependent manner, and that it is also accumulated
      in acidic compartments of rat thymocytes and neuroblastoma cells. A concentration
      of THA less than 1 mM dissipated the pH gradient (delta pH) in all the above
      mentioned in vitro systems. On the contrary higher concentrations of PHS (1-2 mM)
      were ineffective. The accumulation of THA in acidic organelles of the cell may be
      relevant for the pharmacological action of THA in Alzheimer's treatment.

PMID- 7727537
TI  - Hutchinson-Gilford progeria types defined by differential binding of lectin DSA.
AB  - Hutchinson-Gilford Progeria Syndrome (progeria) is an extremely rare childhood
      disorder characterized by precocious senility which presents features similar to
      those seen in human aging. We have previously described a consistent increase of
      the glycoprotein gp200 in progeria skin fibroblasts in vitro. Here we extend
      these glycosylation studies and present evidence for the existence of two types
      of progeria skin fibroblasts. These two forms, called D- and D+, are
      distinguished by their response to the lectin DSA. In the D- group, DSA bound
      glycoproteins from progeria fibroblast strains AG03513B and AG10750 with markedly
      lower affinities compared with glycoproteins from three control fibroblast
      strains. In the D+ group, DSA binding to glycoproteins from four other progeria
      strains AG01972A, AG06297A, AG06917 and AG03198, was comparable to controls.
      Discrimination by DSA is the most distinctive feature of the D- and D+ groups, in
      contrast to binding of lectins Con A, GNA, PHA-L, RCA120, AAA and PNA which show
      no such selectivity. The data are consistent with a model of altered
      glycosylation in the D- type of progeria fibroblasts.

PMID- 7727538
TI  - Protein kinase activities in Leishmania aethiopica: control by growth,
      transformation and inhibitors.
AB  - Promastigotes of L. aethiopica express an ectokinase activity preferring histone
      V-S as substrate. A soluble kinase activity utilizing protamine and histone V-S,
      as well as a particulate fraction associated kinase activity preferring protamine
      are also expressed. The soluble histone kinase activity, but not the ectokinase,
      was expressed at a higher level in cells from late phases of growth, as compared
      to early log phase cultures. Transformation of L. aethiopica to an amastigote
      like stage, resulted in almost complete loss of the kinase activities, with
      retained viability of the cells. Formycin-ATP only weakly inhibited the kinases
      while effectively inhibiting cell growth and thymidine incorporation.
      Staurosporin efficiently blocked the kinase activities and cell growth without
      affecting thymidine incorporation.

PMID- 7727539
TI  - The functional role of glutamine-280 and threonine-282 in human alpha
      galactosidase.
AB  - Our previous study on chimeric mutants of alpha-galactosidase suggested that two
      peptide regions encoded by exons 1-2 and 6 of the enzyme gene contribute to
      substrate recognition (Ishii, S. et al. (1994) Biochim. Biophys. Acta 1204, 265
      270). In this study, we constructed five single amino acid substitutions for
      functional analysis of the amino acid residues around glutamine-279, the mutation
      site detected in an atypical Fabry disease patient. Two mutants, Q280S (Gln280-
      >Ser; CAA-->TCA) and T282A (Thr282-->Ala; ACT-->GCT), showed increased Km and
      decreased thermostability as compared with normal enzyme. Circular dichroism
      spectrum was not modified. An additional chimeric mutation in the exon 1-2 region
      by substitution with the homologous sequence of alpha-N-acetylgalactosaminidase
      cDNA restored catalytic activity and thermostability in both mutants. These data
      indicated the functional significance of glutamine-280 and threonine-282 for
      expressing the activity and stability of alpha-galactosidase molecule, and also
      the presence of an intramolecular interaction between the two peptide regions
      encoded by exons 1-2 and 6.

PMID- 7727540
TI  - Further studies of the in vitro activity of synthetic gliadin peptides in coeliac
      disease.
AB  - Studies of in vitro activity of synthetic peptides derived from the A-gliadin
      structure were carried out using assays based on cultures of foetal chick
      intestinal mucosa and on incubation with rat liver lysosomes. The peptide
      corresponding to residues 11-19, displayed very high activity in the chick
      intestinal assay, but was only weakly active in the lysosomal assay. Peptide 9-19
      was highly active in the chick intestinal assay but was only mildly active in the
      lysosomal assay. Peptide 8-19 was still appreciably active in both assays. The
      results on this group of peptides suggest the importance of residues 8-12 to
      activity and possibly also of a N-terminal glutamine residue. The peptide 213
      227, found in a sub-fraction of fraction 9, was only weakly active in both
      assays, indicating that the PSQQ motif was not solely responsible for toxicity.
      Thus, as the peptide 208-219 was shown previously to be active in the chick
      intestinal assay, it is likely that the 208-212 region of this peptide is of
      prime importance in conferring activity. The results show, for the first time,
      that a nonapeptide from the N-terminal region of A-gliadin is very active in an
      in vitro model of toxicity in coeliac disease.

PMID- 7727541
TI  - In vitro administration of ergothioneine failed to protect isolated ischaemic and
      reperfused rabbit heart.
AB  - Ergothioneine, a natural thiol-containing molecule, has recently been proposed to
      protect the heart against damage caused by ischaemia and reperfusion. We
      investigated the possibility that ergothioneine can have a role in maintaining
      the myocardial thiol/disulfide balance and consequently also a protective effect
      against ischaemic and reperfusion injury. We used isolated Langendorff-perfused
      rabbit hearts subjected to 45 min global and total ischaemia followed by 30 min
      reperfusion at baseline coronary flow (22 ml/min). Ergothioneine was delivered at
      10(-5) M and 10(-4) M 60 min before ischaemia and during reperfusion. Myocardial
      damage was determined in terms of mechanical function, creatine kinase (CK) and
      lactate release, energy phosphate stores and the occurrence of oxidative stress.
      In our experimental conditions the treatment was unable to prevent myocardial
      damage. Ergothioneine, independently from the dosage used, failed to: (i)
      increase recovery of developed pressure upon reperfusion (14.4 +/- 2.3 mmHg in
      control hearts vs. 10.3 +/- 2.9 and 12.5 +/- 2.3 mmHg in 10(-5) M and 10(-4) M
      ergothioneine treated hearts, respectively); (ii) decrease the rise in diastolic
      pressure (44.3 +/- 4.4 mmHg in control hearts vs. 49.8 +/- 5.8 and 48.0 +/- 7.7
      mmHg in treated hearts); (iii) decrease the release of CK and lactate; (iv)
      increase the levels of adenosine triphosphate (ATP) and creatine phosphate (CP)
      in tissue upon reperfusion; (v) maintain ratio between oxidized and reduced forms
      of adenine nucleotide coenzyme, as index of aerobic metabolism; (vi) prevent the
      decline of reduced glutathione (GSH), or the accumulation of oxidized glutathione
      (GSSG) as an index of oxidative stress.

PMID- 7727542
TI  - Calcium and protein kinase C play an important role in Campylobacter jejuni
      induced changes in Na+ and Cl- transport in rat ileum in vitro.
AB  - The pathophysiological mechanism of Campylobacter jejuni (enterotoxigenic)
      induced secretory diarrhoea remains least understood. To investigate the
      mechanism(s) involved, the unidirectional fluxes of Na+ and Cl- were measured
      across the C. jejuni live culture infected and control (non infected) rat ileum
      (unstriped), in vitro by Ussing technique under short circuit conditions, in the
      presence or absence of: Ca2+ ionophore A23187 (5 microM), 1-verapamil (100
      microM), calmodulin (CaM) antagonist W-7 (100 microM), dantrolene (25 microM),
      protein kinase C (PKC) activator PMA (100 ng/ml) and H-7 (60 microM), selective
      inhibitor of PKC. There was net absorption of Na+ and enhanced Cl- secretion in
      infected animals while in control animals there was net absorption of Na+ and
      marginal secretion Cl-.Ca2+ ionophore A23187 mimicked the effects of C. jejuni
      infection whereas 1-verapamil had significant antisecretory effect on Na+ and Cl-
      secretion in infected animals. In vitro measurement of undirectional 45Ca fluxes
      in Ussing chamber experiments revealed net absorption of Ca2+ in infected rat
      ileum as compared to net secretion of Ca2+ in control rat ileum. These
      observations clearly indicate that there is increased stimulation of Ca2+ uptake
      from extracellular milieu to the enterocytes during C. jejuni-induced diarrhoea.
      The intracellular calcium levels (Ca2+]i (as measured by fluorescent probe Fura
      2AM) were found to be raised significantly (P < 0.0001) in enterocytes isolated
      from C. jejuni infected ileum as compared to the enterocytes from control ileum.
      The observed increase in [Ca2+]i in enterocytes isolated from C. jejuni live
      culture supernatant treated rat ileum further shows the involvement of
      enterotoxin in diarrhoeal process. Dantrolene decreased significantly C. jejuni
      induced net Na+ and Cl- secretion but it could not reverse it to absorption
      suggesting the partial involvement of Ca2+ mobilised from intracellular stores in
      mediating secretion. W-7 failed to inhibit the C. jejuni-induced net Na+ and Cl-
      secretion. In addition the CaM activity estimated in intestinal microvillar core
      remained same in both the control and C. jejuni infected animals. This indicates
      that C. jejuni-induced diarrhoea is not mediated through the activation of Ca(2+)
      CaM complex pathway of the Ca2+ messenger system. The PKC activator PMA, induced
      net secretion of Na+ and Cl- in the control animals but it could not enhance
      further the C. jejuni-induced Na+ and Cl- secretion, suggesting that there is
      overlapping effect of PMA and C. jejuni live culture infection.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7727543
TI  - Altered kinetics of cytochrome c oxidase in a patient with severe mitochondrial
      encephalomyopathy.
AB  - Deficiency of cytochrome c oxidase activity was established in a girl born to
      consanguineous parents. She showed symptoms of dysmaturity, generalized
      hypotonia, myoclonic seizures and progressive respiratory failure, leading to
      death on the seventh day of life. Structural abnormalities of the central nervous
      system consisted of severe cerebellar hypoplasia and optic nerve atrophy.
      Biochemical analysis of a muscle biopsy specimen demonstrated deficiency of
      cytochrome c oxidase activity. Cultured fibroblasts from this patient also showed
      a selective decrease in the activity of cytochrome c oxidase, excluding a muscle
      specific type of deficiency. Further investigations in cultured fibroblasts
      revealed that synthesis, assembly and stability of both the mitochondrial and the
      nuclear subunits of the enzyme were entirely normal. The steady-state
      concentration of cytochrome c oxidase in the fibroblasts of the patient was also
      normal, suggesting that the kinetic properties of the enzyme were altered.
      Analysis of the kinetic parameters of cytochrome c oxidase demonstrated an
      aberrant interaction between cytochrome c oxidase and its substrate, cytochrome
      c, most likely because of a mutation in one of the nuclear subunits of the
      enzyme.

PMID- 7727544
TI  - Membrane protein alterations in rodent erythrocytes and synaptosomes due to aging
      and hyperoxia.
AB  - We have applied the technique of electron paramagnetic resonance (EPR) protein
      specific spin labeling to the study of membrane protein alterations occurring
      during age and exposure to isobaric hyperoxia. Cortical synaptosomes and
      erythrocyte membranes (ghosts) were isolated from young rodents (Fisher 344 rats
      or mongolian gerbils, 3-4 months of age) and aged rodents (age 22-27 months for
      rats, greater than 15 months for gerbils). Membrane proteins were spin labeled
      with the thiol-specific spin label MAL-6 (2,2,6,6,-tetramehtyl-4-maleimido
      piperdin-1-oxyl). The relevant EPR spectral parameter of MAL-6 labeled membranes,
      the W/S ratio, decreased significantly with age of animal in both synaptosomes
      and ghosts (P < 0.001). As a paradigm for accelerated oxidative stress, young and
      aged gerbils were exposed to an atmosphere of 90-100% O2 for 0-48 h. In both
      young and aged gerbils, the W/S ratio decreased significantly with hyperoxic
      stress (P < 0.003). The W/S ratio of synaptosomes isolated from aged gerbils
      decreased continually from 0-48 h hyperoxia, whereas the W/S ratio of
      synaptosomes from young animals demonstrated a pronounced rebound effect from 24
      48 h. The results are discussed with reference to membrane protein oxidation in
      aging.

PMID- 7727545
TI  - A novel polymorphism in the human acid sphingomyelinase gene due to size
      variation of the signal peptide region.
AB  - Acid sphingomyelinase (ASM) is the lysosomal enzyme required to hydrolyze
      sphingomyelin into ceramide and phosphocholine. In man, a deficiency of this
      enzymatic activity leads to Types A and B Niemann-Pick disease (NPD), a panethnic
      disease with a relatively high incidence among Ashkenazi Jewish individuals.
      Analysis of the ASM cDNA and genomic sequences revealed a unique hexanucleotide
      sequence, CTGG(TC)(GT), located within the signal peptide region of the ASM
      polypeptide (corresponding to the hydrophobic amino acid sequence LVLALALALALA).
      Notably, five hexanucleotide repeat units were found in the full-length cDNA,
      while the genomic sequence contained six, suggesting that this region of the ASM
      gene may be polymorphic. PCR primers were designed to amplify the repeat region
      and over 700 normal and NPD ASM alleles were analyzed among Ashkenazi Jewish and
      non-Jewish populations. Five alleles were identified corresponding to nine,
      seven, six, five and four hexanucleotide repeats, respectively. The allele
      frequencies were similar among Jewish and non-Jewish populations and no
      differences were found among normal individuals and Type A and B NPD patients.
      Thus, it does not appear to be a common cause of NPD. This intriguing repeat
      polymorphism should be extremely useful to researchers interested in gene
      identification and characterization of the chromosomal region 11p15.1-p15.4, as
      well as individuals interested in the biology of this important lysosomal
      hydrolase.

PMID- 7727546
TI  - Direct sequencing of PCR amplified pig PrP genes.
AB  - The protein coding regions of the PrP genes of six pigs were sequenced directly
      from PCR-amplified genomic DNA. All six sequences were identical. The gene
      encodes a protein of 257 amino acids and shows an overall similarity of 77 to 88%
      with the PrP sequences from other mammalian species. The significance of amino
      acids unique to the pig PrP are discussed.

PMID- 7727547
TI  - Enzymatic amplification and molecular cloning of cDNA encoding the small and
      large subunits of bovine interleukin 12.
AB  - cDNA generated from stimulated abomasal lymph node cells was used to amplify and
      clone the 35 kDa and 40 kDa subunits of bovine interleukin 12 (IL-12) using
      primers derived from semi-conserved regions between human and mouse IL-12
      sequences. The deduced amino acid sequence of the 40 kDa subunit demonstrated
      84.4% and 67.6% homology with human and mouse sequences, respectively. The
      deduced sequence of the 35 kDa subunit exhibited comparable similarities to the
      human 35 kDa subunit (82.2%) but differed significantly (58.6%) from mouse
      derived sequences.

PMID- 7727549
TI  - The pitfalls of clinical acupuncture research: can east satisfy west?

PMID- 7727548
TI  - Association of Rheumatology Health Professionals president's report for 1993.

PMID- 7727550
TI  - Acupuncture for the treatment of pain of osteoarthritic knees.
AB  - OBJECTIVE: The purpose of this study was to determine whether acupuncture was
      more effective than sham acupuncture in the reduction of pain in persons with
      osteoarthritis (OA) of the knee. METHODS: Forty subjects (20 men, 20 women) with
      radiographic evidence of OA of the knee were stratified by gender and randomly
      assigned to either the experimental (real acupuncture) or control (sham
      acupuncture) groups. Subjects were treated three times per week for 3 weeks and
      evaluated at three test sessions. Outcome measures were: 1) the Pain Rating Index
      of the McGill Pain Questionnaire, 2) the Western Ontario and McMaster
      Universities (WOMAC) Osteoarthritis Index, and 3) pain threshold at four sites at
      the knee. RESULTS: The analyses of variance showed that both real and sham
      acupuncture significantly reduced pain, stiffness, and physical disability in the
      OA knee, but that there were no significant differences between groups.
      CONCLUSIONS: Acupuncture is not more effective than sham acupuncture in the
      treatment of OA pain.

PMID- 7727551
TI  - Physical performance characteristics of women with fibromyalgia.
AB  - OBJECTIVE: The aim of this study was to examine physical performance in women
      with fibromyalgia (FM) using methods that are easy to use in clinical settings
      and to compare our findings with published norms or a healthy comparison group.
      METHODS: Measures of shoulder pain and range-of-motion, isometric shoulder
      endurance, neck rotation, leg strength, hand grip strength, back flexibility, 6
      minute walk distance, and symptom duration were completed on 97 subjects with FM.
      The comparison group was 30 age-matched healthy women. RESULTS: The FM group had
      significantly lower physical functioning scores on all variables when compared to
      the healthy group or published norms. When pain at rest was controlled, pain on
      motion was the most significant predictor of variance in shoulder range of
      motion, whereas range of motion was the most significant predictor of right
      shoulder endurance and grip strength of both hands. CONCLUSIONS: Women with FM
      are markedly below average in physical performance abilities when measured by
      clinical tests.

PMID- 7727552
TI  - Weather, beliefs about weather, and disease severity among patients with
      fibromyalgia.
AB  - OBJECTIVE: This investigation 1) examined the relationships among actual weather,
      disease severity, and symptoms for individuals with fibromyalgia, 2) assessed
      subjects' beliefs about weather affecting their symptoms, and 3) examined
      differences between individuals with high and low "weather sensitivity." METHODS:
      Eighty-four individuals meeting Yunus' criteria for the diagnosis of fibromyalgia
      participated. Subjects completed the Weather and Pain Questionnaire (WPQ), the
      Arthritis Impact Measurement Scales (AIMS), the Symptom Checklist-90-Revised (SCL
      90-R), and a Visual Analog Scale (VAS) assessing pain. A tender point index and a
      myalgic score were also obtained. RESULTS: Subjects reported that weather
      affected musculoskeletal symptoms predominantly. The strongest relationship was
      found between weather beliefs and self-reported pain scores. Subjects with high
      weather sensitivity tended to have more functional impairment and psychological
      distress.

PMID- 7727553
TI  - An educational needs assessment of children with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: Our objective is to describe the use of the PRECEDE model
      (predisposing, reinforcing, and enabling causes in educational diagnosis and
      evaluation) to organize needs assessment data in order to define self-management
      behaviors and plan an educational intervention for children with juvenile
      rheumatoid arthritis (JRA) and their families. METHODS: Analysis was done of
      needs assessment data collected from several sources: 1) literature review, 2)
      survey of parents of 51 children with JRA, 3) group interview of seven parents of
      children with JRA, 4) results of pilot programs, and 5) clinical experience of an
      interdisciplinary pediatric rheumatology team. RESULTS: Two sets of interrelated
      behavioral factors were identified through the needs assessment: 1) those related
      to managing the school environment to facilitate optimal participation and to
      minimize school-related disability, and 2) those related to treating pain and
      stiffness, intervening in the disease process, and preserving joint function.
      CONCLUSION: Both of these sets of behavioral factors may be related to the
      optimization of children's mobility, joint function, and autonomy of activities
      of daily living and should be targets of an educational intervention.

PMID- 7727554
TI  - A descriptive study of foot problems in children with juvenile rheumatoid
      arthritis (JRA).
AB  - In this study, we evaluated the feet of 144 consecutive children with juvenile
      rheumatoid arthritis (JRA) during a routine outpatient visit to discover patterns
      of foot problems. We found that all but nine subjects had at least 1 of 21 foot
      problems, categorized as inflammation, limitation of motion, and abnormal
      alignment. Overall, pronated rearfoot and midfoot were observed in 73% and 72% of
      JRA patients, respectively. Additionally, 36% had splayfoot, whereas 35% of
      subjects had ankle limitation of motion. Other common foot problems included
      pronated forefoot, rearfoot and forefoot synovitis, forefoot limitation of
      motion, and toe valgus. Significant differences in the occurrence of various foot
      problems were observed among JRA onset/course subgroups and were influenced by
      both age and disease duration. Specifically, subjects with polyarticular JRA had
      more forefoot limitation and toe valgus, whereas subjects with pauciarticular JRA
      had pronated forefoot more often. Ankle limitation of motion, although unrelated
      to the JRA sub-group, was related to the duration of JRA. Subjects with longer
      disease histories also had toe valgus more often. Conversely, forefoot limitation
      of motion seemed to be more a function of age than of disease duration. These
      results indicate that foot problems are common in the JRA population, and they
      underscore the need for thorough evaluation and physical therapy management.

PMID- 7727555
TI  - Preferred intraarticular corticosteroids and associated practice: a survey of
      members of the American College of Rheumatology.
AB  - OBJECTIVE: To determine which intraarticular steroids are used by rheumatologists
      and whether this use and associated practice vary with time and place of
      training. METHOD: American College of Rheumatology members were mailed
      questionnaires that focused on steroid use in the adult knee. RESULTS: The
      steroids favored by the respondents were methylprednisolone acetate (MPA),
      preferred most by those trained in the eastern U.S.; triamcinolone hexacetonide
      (TH), preferred by those trained in the Midwest and Southwest; and triamcinolone
      acetonide (TA), preferred by those trained in the West. Only TH was chosen
      primarily because of efficacy. Regardless of concentration, respondents used 1 ml
      of steroid. Most (especially those recently trained) combined steroid with local
      anesthetic. Post-injection instructions varied: 29% did not restrict weight
      bearing; 8% recommended limited weight-bearing for 1 week or more. CONCLUSION:
      MPA, TH, and TA were favored. Associated techniques varied, based in part on
      where and when training took place. Research is needed to provide a more rational
      basis for clinical practice.

PMID- 7727556
TI  - Issues in meta-analysis: an overview.
AB  - A summary is provided for the relevant issues that investigators must address
      when wishing to synthesize data via a meta-analysis. The analogy is made to
      conducting a clinical trial and its components. Both design and statistical
      issues are discussed with the goal of assuring that the proper elements are
      included in the meta-analysis. Further, global concerns are presented so that the
      researcher is aware of the clinical controversies faced when conducting a meta
      analysis. Finally a comparison is made of the advantages and disadvantages of a
      large-scale clinical trial versus a meta-analysis.

PMID- 7727557
TI  - Post-traumatic fibromyalgia: a case report narrated by the patient.
AB  - This report describes a case of fibromyalgia developing following a workplace
      injury, but in which the issues of compensation and work disability were not
      relevant. A previously healthy 37-year-old woman developed back and groin pain
      after lifting a heavy box. Over the next months, pain and allodynia gradually
      spread over her body, and headaches, sleep disturbance, paresthesias, and bowel
      symptoms developed for the first time. The pain was constant and severe, invading
      and interfering with every area of daily function. Surprisingly, no previous case
      reports or definition of post-traumatic fibromyalgia could be found. This case
      report, narrated by the patient, suggests that there is such an entity as post
      traumatic fibromyalgia, and that central nervous system plasticity plays a
      central role.

PMID- 7727558
TI  - Keeping our guard up.

PMID- 7727559
TI  - Human breast milk and facilitation of gastrointestinal development and
      maturation.
AB  - Breast milk feedings make important contributions to optimal infant intestinal
      maturation. The current literature provides support for many important benefits
      attributable to breastfeeding. Breast milk feedings encourage helpful intestinal
      bacterial colonization and assist in development of the intestinal mucosa
      barrier. More importantly, breastfeeding provides immunologic properties that are
      delivered directly to the infant's intestinal mucosa. Breastfeeding also seems to
      have a protective effect in preventing allergic conditions.

PMID- 7727560
TI  - Patient teaching methods and materials.
AB  - As a result of the current healthcare politics, nurses are taking a closer look
      at methods to support self-care and wellness. In this article, the author
      discusses methods, materials, cost, and problems of patient education. There are
      barriers to effective patient education. Nurses need to overcome these barriers
      and choose the most effective method and materials for teaching patients.

PMID- 7727561
TI  - SGNA endoscopic disinfectant survey.
AB  - The purpose of this study was to describe the prevalence of health problems, use
      of protective attire, and health surveillance practices in a large group of
      healthcare workers exposed to glutaraldehyde. The results revealed that 37.8% of
      respondents reported at least one symptom/illness before exposure to
      glutaraldehyde. Nearly 60% of respondents reported symptoms/illnesses after
      glutaraldehyde exposure. Healthcare workers employed > or = 5 years tended to
      report fewer health problems preexposure and slightly more problems postexposure
      compared with all respondents. Surprisingly, smokers reported a nearly equal
      number of symptoms/illnesses both pre- and postexposure when compared with the
      total group. Approximately 95% of respondents always wore gloves, usually latex;
      52% always wore moisture-proof outer wear; 28% always wore masks; and 55% always
      wore eye protection when exposed to glutaraldehyde. Those who used protective
      attire reported as many symptoms/illnesses as those who did not. Healthcare
      workers need to demand that the ambient glutaraldehyde level in the endoscopy
      cleaning area be checked periodically and records of these checks kept.
      Manufacturers need to produce more effective protective attire. Employers need to
      purchase protective attire for employees, and employees need to wear it until
      alternative endoscopic disinfectant/sterilization methods can be found.

PMID- 7727562
TI  - Infantile alpha 1 antitrypsin deficiency: a case report.
AB  - Using a case study format, the authors describe an infant with an unusual
      metabolic disorder, Alpha 1 Antitrypsin Deficiency. It is rare to find an infant
      in whom such significant liver and pulmonary disease develops before his first
      birthday. In this article the authors describe the pathophysiology, genetics,
      diagnosis, and treatment of this disorder. The nursing diagnoses alteration in
      nutrition, alteration in skin integrity, ineffective airway clearance, and
      potential for ineffective family coping are the framework used to describe the
      nursing care.

PMID- 7727564
TI  - Computers in nursing: the future revisited.

PMID- 7727563
TI  - The endoscopy technician: a valuable resource.

PMID- 7727565
TI  - Understanding published research reports, or how to "study" a study.

PMID- 7727566
TI  - Antibiotic prophylaxis in patients undergoing endoscopic procedures.

PMID- 7727567
TI  - SGNA approver/provider status official.

PMID- 7727568
TI  - Esophageal bezoar formation in a tube-fed patient receiving sucralfate and
      antacid therapy: a case report.
AB  - In this case report, the authors describe an esophageal bezoar found in a
      mechanically ventilated patient receiving sucralfate, antacid, and tube feeding
      via a nasogastric tube. The presence of a prosthetic device in the esophagus
      (such as a nasogastric or endotracheal tube) in conjunction with functional
      esophageal abnormalities is a common link in the development of esophageal
      bezoars. These bezoars form in the esophagus as a result of regurgitation of
      stomach contents. In addition, bezoars are a known complication of gastric
      motility disorders, such as gastric paresis of diabetes. Critically ill patients
      are frequently given antacid and sucralfate therapy while being enterally tube
      fed, often by nasogastric tubes. This combination of treatment modalities in
      patients with esophageal and/or neurological abnormalities warrants vigilant
      adherence to measures to prevent reflux and gastric pooling.

PMID- 7727569
TI  - Electrocautery and patients with implanted cardiac devices.
AB  - Implanted cardiac devices, pacemakers, and automatic cardioverter/defibrillators
      are becoming more common in the general population. There are more than one-half
      million persons with pacemakers living in North America, and approximately 20,000
      patients have received automatic implantable cardioverter/defibrillators. As
      pacemaker and defibrillator patients experience common gastrointestinal
      afflictions, it is likely that more will require endoscopic procedures.
      Appropriate precautions must be undertaken during electrosurgical procedures in
      order to avoid damage and interruption of pacemaker/defibrillator devices.
      Through careful assessment, intervention, and discharge planning, the GI nurse
      and associate can reduce electrosurgical risks to the gastrointestinal patient
      with an implanted cardiac device. Specific recommendations for preprocedure
      patient assessment and intraprocedure interventions are discussed, and an actual
      case is presented to illustrate a successful plan of care.

PMID- 7727570
TI  - Case studies as a research method.
AB  - Nurses in any field have numerous opportunities for research. Nursing research is
      undertaken to solve specific clinical dilemmas. Case studies may be a reasonable
      choice for the nurse involved in patient care. Following one subject may be less
      overwhelming than studying an entire population of subjects. Case studies provide
      an in-depth look at a single subject over time. The results of this in-depth
      analysis can be applied to a standard of care in order to improve clinical
      practice. Case studies may also be the first step toward a larger research
      project.

PMID- 7727571
TI  - "Oh no, the patient is six, not sixty!": the pediatric endoscopy patient.
AB  - The success of a pediatric endoscopic procedure from the point of view of both
      the nurse and the child depends on many factors. It is necessary for the nurse to
      prepare the pediatric patient both physically and emotionally. The physical
      preparation includes diet orders, colon preps, and venipuncture techniques. The
      emotional preparation includes preparing the pediatric patient in a
      developmentally appropriate manner. Nurses facilitate the child's tolerance of
      the procedure through the processes of trust, understanding, and mastery. These
      preparations are viewed as essential in order for the child to integrate this
      medical experience into his/her already existing repertoire of experiences as
      positive. Conscious sedation and recommendations for monitoring child safely are
      important pediatric considerations, as are recovery and discharge instructions. A
      table for pediatric vital signs, an endoscopy unit scoring sheet, and sample
      discharge instructions are included in this article. The information presented in
      this article can help the experienced pediatric nurse, as well as the nurse who
      only occasionally cares for the pediatric patient, make the endoscopy procedure
      more successful.

PMID- 7727572
TI  - Diagnostic laparoscopy of the liver and peritoneum using conscious sedation.
AB  - Laparoscopic study of the liver is now common in many U.S. medical centers. With
      proper preparation, the procedure can be performed safely in the endoscopy suite
      using conscious sedation. Multiple sites in the liver can be biopsied in a
      directed and rapid sequence. Postbiopsy bleeding can be detected early and
      stopped effectively should it occur. Restrictions after the procedure are similar
      to those for other outpatient surgical procedures along with the typical post
      liver biopsy instructions. A successful laparoscopy requires careful nursing
      evaluation, monitoring, and assistance. In this article, the authors discuss the
      practical aspects of diagnostic laparoscopy performed in the endoscopy suite, the
      nurse's role during and after the procedure, and management of the instruments.

PMID- 7727573
TI  - Celiac disease in childhood.

PMID- 7727574
TI  - The most commonly prescribed medications in the United States.

PMID- 7727575
TI  - The art of being a GIA.

PMID- 7727576
TI  - The sexual transmission of hepatitis C virus.

PMID- 7727577
TI  - Why do condoms break or slip off in use? An exploratory study.
AB  - Men attending 3 sexually transmissible disease clinics and a university health
      clinic in Sydney, Australia, were invited to complete a questionnaire on their
      use of condoms. Respondents were 108 male condom user volunteers aged 18 to 62
      years; in the last five years 47 had had sex with men, 18 with both men and women
      and 43 only with women. They reported using a total of 4809 condoms in the
      previous 12 months (condoms worn by a male partner were not included). The
      overall breakage rate was 4.9% (including condoms breaking during application),
      while 3.1% of condoms reportedly slipped off. On a multivariate analysis, condom
      breakage correlated with: (1) male sexual partner(s), (2) infrequent condom use,
      (3) rolling the condom on as per conventional instructions (modified application
      methods appeared protective) and (4) having trouble with condoms partially
      slipping. Factors associated with condoms slipping off were (1) young age, (2)
      being circumcised, (3) having less life-time condom experience, (4) rolling the
      condom on conventionally, and (5) having trouble with condoms partially slipping.
      Few men used inappropriate lubricants and no association between lubricant type
      and breakage was found. Though common among our respondents, negative attitudes
      towards condoms, loss of erection during condom application or use, finding
      condoms uncomfortable, and prolonged sexual intercourse were not related to
      success in use. Almost half (49%) of the men reported having deliberately removed
      a condom after the beginning of intercourse; 17% had done so 3 or more times.
      Counselling protocols should acknowledge the complexity of condom use.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7727578
TI  - A comparison of zidovudine, didanosine, zalcitabine and no antiretroviral therapy
      in patients with advanced HIV disease.
AB  - Three nucleoside analogues, zidovudine (AZT), didanosine (ddI), and zalcitabine
      (ddC), are approved for use in the treatment of patients with HIV infection. This
      retrospective study compares the 3 drugs and examines the overall utility of
      antiretroviral therapy by way of comparisons to a no treatment (No Rx) group in
      patients with advanced HIV disease. Patients with advanced HIV disease were
      enrolled in didanosine (August 1989-December 1990) or zalcitabine (October 1990
      February 1992) expanded access programmes; continued on zidovudine treatment
      despite fulfilling criteria for zidovudine failure or intolerance; or maintained
      on no antiretroviral treatment. Statistical analysis revealed that patients on
      nucleoside analogue therapy had fewer opportunistic infections (P = 0.001) than
      those who received no antiretroviral treatment. The Kaplan-Meier 12-month
      estimate of survival was significantly longer among patients who switched from
      zidovudine to zalcitabine but not among patients who switched to didanosine, when
      compared to the other 2 groups (P = 0.05).

PMID- 7727579
TI  - Chlamydial urethritis in heterosexual men attending a genitourinary medicine
      clinic: prevalence, symptoms, condom usage and partner change.
AB  - A prospective study of 356 consecutive heterosexual male patients attending the
      Department of Genitourinary Medicine at University College Hospital was carried
      out to determine the prevalence of Chlamydia trachomatis. Patients were asked
      about their symptoms, use of condoms and change of sexual partner. The prevalence
      of non-gonococcal urethritis (NGU--chlamydia positive and negative urethritis)
      was 37% (131 of 356). C. trachomatis was shown to be the causative organism in
      24% (31 of 131) of patients with NGU. The prevalence of other STDs in men with C.
      trachomatis and with non-chlamydial urethritis was 15% and 10% respectively. Men
      with C. trachomatis were significantly more likely than men with non-chlamydial
      urethritis to be asymptomatic (56% vs 35%). The prevalence of C. trachomatis was
      highest in men who had changed partner in the previous 3 months (20 of 32 men). A
      third of men never used condoms in the first 3 months of a new relationship and
      over half failed to use them after 3 months. There was no evidence that the
      reported use of condoms reduced the rate of infection with C. trachomatis.

PMID- 7727580
TI  - Sexual behaviour in the city of Lisbon.
AB  - This study of sexual behaviour in the city of Lisbon is based on data obtained
      from 2 random samples, one of individuals aged 16-20 (n = 400) and another of
      individuals over the age of 20 (n = 400). Samples have been stratified by
      district, gender and age. Data were obtained by personal interview and by
      questionnaires completed confidentially by the interviewees. The data include the
      age of first sexual intercourse, the number of sexual partners, the prevalence of
      casual relations and the type of sexual practices according to sex and age group.
      Results show that despite the high risk of exposure to HIV in a significant
      percentage of the population, AIDS is seen as a personal threat by only 20% of
      the population. Six per cent of the adults (aged 21 and over) and 12% of the
      young people (16-20) replied that they had not yet considered the problem; 73.5%
      of the adults and 67.4% of the young people stated that they did not feel
      threatened by the disease. Data suggest that the differences between men and
      women have decreased. Among the sexually active population, only 12% of
      individuals under 21 and 8% of the adults use condoms regularly. The awareness of
      infidelity among couples is much lower than in reality.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7727581
TI  - Ulcerative disease of the anorectum in AIDS.

PMID- 7727582
TI  - Syphilis and HIV infection among prisoners in Maputo, Mozambique.
AB  - A cross-sectional study was carried out among 1284 male and 54 female prisoners
      to assess the prevalence of and risk factors for sexually transmitted diseases
      (STD) in 4 correctional institutions of Maputo, Mozambique. Among the men, 32%
      reported a history of prostitute contact and 41% reported a history of STD. Only
      9% reported having ever used condoms. Seventy (5.5%) men reported having had
      sexual intercourse while in prison, in all but one instance this involved sex
      with another man. There was no reported intravenous drug use. One hundred and
      four (7.8%) inmates had positive serological tests for syphilis and 8 (0.6%) had
      antibodies to HIV. Among men, syphilis was associated with a history of genital
      ulcer [odds ratio (OR) = 3.1, 95% confidence interval (CI) = 1.4, 6.4] and
      uncircumcised status (OR = 1.5, 95% CI = 1.0, 2.5). This study demonstrates that
      syphilis is common among inmates in Maputo and that risk behaviours for STD
      transmission exist within Maputo prisons. There is a need for STD screening and
      treatment programmes within prisons in Mozambique and the introduction of
      educational interventions, including condom promotion.

PMID- 7727583
TI  - Experience of HIV disease in a London District General Hospital.
AB  - The aim of this paper is to describe and discuss the experience of HIV disease in
      Central Middlesex Hospital, London up to June 1993. A retrospective study of the
      total number of HIV-positive patients cared for was performed. In addition,
      prospectively collected data as part of local epidemiological surveillance from
      January 1987 to June 1993 on all HIV test requests was analysed. Between January
      1987 and June 1993 3695 individuals were tested for HIV-1 antibody at Central
      Middlesex Hospital. Of these, 101 HIV-1 seropositive individuals were identified
      and have attended this District General Hospital. Seven HIV-1 seropositive
      individuals were identified from before December 1986. Sixty (56%) had acquired
      their infection heterosexually. Thirty-eight (35%) originated from the UK and 47
      (44%) from sub-Saharan Africa; the remaining 23 (21%) originated from the rest of
      Europe, South America and the Caribbean. Thirty-four (31%) of the patient group
      developed AIDS during follow-up at the hospital and in 26 individuals AIDs
      developed within 2 months of their first positive HIV result. The mean survival
      of 20 patients after AIDS-defining diagnoses was 7 months 18 days. This
      unselected group of HIV-1 seropositive patients present late in the course of
      their HIV disease and survival following AIDS is poor.

PMID- 7727584
TI  - HIV seroconversion illness after orogenital contact with successful contact
      tracing.

PMID- 7727585
TI  - Unusual manifestations of early syphilis in a married male. Florid manifestations
      of condylomata lata on the face.

PMID- 7727586
TI  - Urethral rupture in a homosexual male following avulsion of a 'Prince Albert'
      penile ring.

PMID- 7727587
TI  - Disseminated candidiasis in two HIV-positive intravenous drug users.

PMID- 7727588
TI  - Screening for hepatitis B, hepatitis C and syphilis at two genitourinary medicine
      clinics.

PMID- 7727589
TI  - Accuracy of computerized diagnostic records for Chlamydia, syphilis, gonorrhoea
      and herpes.

PMID- 7727590
TI  - An audit of pharyngeal infection in patients attending GUM clinic in Sunderland.

PMID- 7727591
TI  - International Union Against the Venereal Diseases and the Treponematoses: an
      overview.

PMID- 7727592
TI  - Report of the Regional Director for North America, International Union Against
      the Venereal Diseases and Treponematoses.

PMID- 7727593
TI  - Referral of cases of gonococcal infection.

PMID- 7727594
TI  - Falling prevalence of Chlamydia trachomatis infection--no time for complacency.

PMID- 7727595
TI  - Developments in the radiological investigation of the lower urinary tract.

PMID- 7727596
TI  - Function and structure in retinal transplants.
AB  - Embryonic mammalian donor retina transplanted into the subretinal space of a
      mature host develops into a graft with well-organized, but atypical retinal
      structure. We tested the effect of this organization on rabbit-to-rabbit graft
      functional properties, isolating the graft to avoid contamination of graft
      responses by host retinal activity. Transient ON or ON-OFF spike-like responses
      and local electroretinograms (L-ERGs) were recorded simultaneously via a single
      electrode on the graft surface. These response components depended on stimulus
      diameter, sometimes in a way indicating antagonistic center-surround receptive
      field organization and spatial tuning (43%). Other times, the responses were an
      increasing function of stimulus diameter which saturated for large spots (57%).
      Response amplitudes were a monotonically-increasing function of light intensity
      over the narrow range tested. The L-ERGs were reminiscent of the proximal
      negative response or M-wave seen in normal retinas, which reflect light-induced
      amacrine cell activity. Thus, for the first time, we have shown that these
      subretinal grafts possess light-transduction and complex functional properties
      like those in normal retinas. They also possess the cellular complement and
      synaptic microcircuitry needed to form these physiological properties, Therefore,
      these results demonstrate a functional ability and capacity in transplants that
      is required if nerve cell transplantation surgery is to be done with therapeutic
      aims.

PMID- 7727597
TI  - Effects of nerve growth factor infusion on behavioral recovery and graft survival
      following intraventricular adrenal medulla grafts in the unilateral 6
      hydroxydopamine lesioned rat.
AB  - NGF was infused into the lateral ventricle of rats with unilateral 6-OHDA lesions
      of the substantia nigra along with adrenal medulla or control grafts. Treatment
      effectiveness, as measured by amphetamine-induced turning behavior, indicated
      that there were no significant differences between treated and control groups in
      spite of the survival of tyrosine hydroxylase (TH) immunoreactive grafts.
      Furthermore, adrenal medulla graft survival was not dependent on NGF infusion.
      These results indicate that TH-positive graft survival is not correlated with
      behavioral recovery as assessed by amphetamine-induced turning. These results
      differ from studies which utilized apomorphine-induced turning as a measure of
      behavioral recovery. We propose that adrenal medulla graft survival alone is not
      sufficient to promote behavioral recovery in the 6-OHDA lesioned rat.

PMID- 7727598
TI  - Intracortical dentate fascia grafts: mossy fiber synapses in the host neocortex.
AB  - Embryonic dentate fascia was grafted into a cavity in the area of the adult rat
      neocortex which represents the vibrissae (barrel field). We wished to test the
      possibility of development of connections between the two brain areas which do
      not have synaptic or tissue contacts in situ. The unique characteristics of the
      giant synaptic boutons of the dentate mossy fibers were used for detection of the
      dentate synaptic contacts with neocortical neurons at the electron microscopic
      level. Ultrastructural analysis nine months postgrafting has shown that the
      bundles of mossy axons enter the host neocortex and develop multiple terminal and
      en passant contacts with typical characteristics. Neuronal perikarya, large
      dendritic trunks and fine caliber terminal dendritic branches were used by the
      mossy fibers as postsynaptic targets, as well as spines of various complexity and
      configurations. The subsynaptic dendrites seemed to be modified by synapsing
      giant boutons. Accumulation of cytoplasmic organelles was observed at these
      sites. Various bumps and protuberances were formed by the subsynaptic dendrite
      surface. The contents of these appendages were variable; some of them contained
      organelles typical of dendroplasm, while others were more spine-like, often with
      inclusion of ribosomes. It is concluded that mossy fibers growing into the host
      neocortex can develop typical contacts with inappropriate targets with all the
      ultrastructural features of functional synapses.

PMID- 7727599
TI  - Ultrastructural signs of regenerative-degenerative processes in long-term dentate
      fascia grafts.
AB  - An ultrastructural investigation of embryonic (E20) dentate fascia grafts
      transplanted into an acute cavity in the somatosensory neocortex of adult rats
      revealed a continuous dynamic state of the tissue nine months postgrafting. The
      grafts consisted mainly of typical granular cells with some admixture of
      hippocampal pyramidal neurons and polymorph hilar cells with a normal, mature
      ultrastructure. Many features of the transplanted tissue suggested continuing
      development and growth. Dendritic branches with growth tips, axonal growth cones,
      synaptic boutons with growth vesicles, immature myelin sheaths and myelin
      producing cells were observed. In contrast, ultrastructural signs of degeneration
      were present in some axons, and, less often, in dendrites. These processes, as
      well as some of the terminal synapses, contained various amounts of lysosomes and
      lipofuscine granules. In many such terminals the signs of degenerative change
      were combined with the presence of multiple mitochondria, polymorph vesicles and
      tubular reticulum, indicating simultaneous reparative processes. It is suggested
      that continuous recycling of neuronal processes occurs in long-term dentate
      grafts. This morphological instability may depend on the paucity of synaptic
      targets within the dentate tissue transplanted with a minimal quantity of
      hippocampal pyramidal cells and on the limitation of the afferent input. However,
      the observed features of the grafted dentate tissue are not qualitatively
      different from those observed in normal dentate with its protracted development
      and active compensatory reorganization.

PMID- 7727601
TI  - Biochemical analysis of peritoneal fluid in patients with and without bacterial
      infection.
AB  - OBJECTIVE: To find out if the concentrations of biochemical variables in
      peritoneal fluid differed in the presence or absence of infection. DESIGN:
      Prospective study. SETTING: University hospital, Switzerland. SUBJECTS: 80
      patients undergoing abdominal operations, 23 of whom were operated on for an
      intra-abdominal infection. 57 Patients with no sign of infection served as
      controls. MAIN OUTCOME MEASURES: Concentrations of 24 biochemical variables
      measured in specimens of peritoneal fluid obtained during the operation. RESULTS:
      Major differences between specimens taken from infected and uninfected patients
      including: glucose 5.4 compared with 0.8 mmol/l, lactate 7.9 and 17.2 mmol/l,
      aspartate aminotransferase 83 and 520 U/l, phosphate 1.1 and 3.7 mmol/l,
      potassium 4.5 and 10.1 mmol/l, lactate dehydrogenase 2021 and 7998 U/l, and gamma
      glutamyl transferase 57 and 169 U/l. CONCLUSION: Intra-abdominal infection
      significantly alters the composition of peritoneal fluid. The assessment of
      milieu factors at the site of infection may help in the design of more predictive
      in vitro tests to guide antimicrobial treatment of intra-abdominal infections. In
      addition, the knowledge of discriminatory variables in peritoneal fluid may be
      useful in the diagnosis of intra-abdominal infection.

PMID- 7727600
TI  - Serum concentrations of interleukin-6, tumour necrosis factor-alpha, and C
      reactive protein in patients undergoing major operations.
AB  - OBJECTIVE: To investigate the kinetics of interleukin-6 (IL-6), tumour necrosis
      factor-alpha (TNF-alpha) and C-reactive protein after a surgical operation.
      DESIGN: Prospective study. SETTING: Teaching hospital, Sweden. SUBJECTS: 28
      patients undergoing cardiac operations, joint replacement, or gastric restrictive
      operations. INTERVENTIONS: Samples of serum were taken before operation; at 0, 6,
      and 12 hours; and then daily for six days. OUTCOME MEASURES: IL-6, TNF-alpha, and
      C-reactive protein concentrations at specified time points, and their correlation
      with complications and outcome. RESULTS: The IL-6 concentration peaked soon after
      operation, and that of C-reactive protein 48-96 hours later. Serum IL-6
      concentrations were highest in the eight patients undergoing cardiac operations.
      In one patient an infective complication occurred resulting in secondary peaks of
      IL-6 and C-reactive protein. Three patients who developed postoperative
      circulatory and respiratory instability had no additional changes in cytokine
      concentrations. The overall concentrations of IL-6 were raised above 100 pg/ml
      for a mean of 36 hours after operation and those of C-reactive protein were over
      100 mg/l for a mean of 106 hours (p < 0.0001). Serum TNF-alpha concentrations
      were low in all patients. CONCLUSION: The maximum serum concentrations of IL-6
      and C-reactive protein after surgical operations were comparable to those in
      patients with sepsis. If IL-6 and C-reactive protein analyses are used in the
      diagnosis of infective complications, evaluation of the results should be related
      to the length of time between the operation and sampling, and to the clinical
      findings. The shorter period during which IL-6 was raised compared with C
      reactive protein indicates that IL-6 may be a more useful marker of postoperative
      infective complications.

PMID- 7727602
TI  - Effect of recombinant human erythropoietin on anaemia after gastrectomy: a pilot
      study.
AB  - OBJECTIVE: To evaluate the role of recombinant human erythropoietin in reducing
      the need for homologous blood transfusion during operations by studying its
      effect on the recovery of postoperative anaemia. DESIGN: Randomised controlled
      trial. SETTING: University hospital, Japan. SUBJECTS: 10 patients with gastric
      cancer undergoing distal gastrectomy. INTERVENTIONS: 5 Patients were given
      erythropoietin 200 IU/kg/day together with ferric pyrophosphate 40 mg/day
      intravenously for seven days before operation and 14 days afterwards, and 5 were
      given ferric pyrophosphate 40 mg/day alone (control group). MAIN OUTCOME
      MEASURES: Packed cell volume, haemoglobin concentration, and white and red cell
      counts. RESULTS: There was no significant change in packed cell volume after the
      operation in the erythropoietin group, but in the control group it dropped from a
      mean (SD) of 0.378 (0.074) before operation to 0.329 (0.068) on day 1 (p < 0.05).
      Haemoglobin concentrations were significantly higher in the erythropoietin group
      than the control group on day 7 (mean (SD) 137 (14) compared with 110 (19) p <
      0.05), and on day 10 (140 (9) compared with 108 (15) p < 0.01) after operation.
      CONCLUSION: Erythropoietin prevented postoperative anaemia after gastrectomy as
      judged by packed cell volume, haemoglobin concentration, and red cell count.
      Erythropoietin given before and after operation therefore has the potential to
      reduce the need for homologous blood transfusion during and after major
      operations.

PMID- 7727603
TI  - Glutamine supplementation does not prevent bacterial translocation after non
      lethal haemorrhage in rats.
AB  - OBJECTIVE: To find out whether supplementation of an enteral diet with glutamine
      would reduce translocation of bacteria to mesenteric lymph nodes or blood after
      major haemorrhage in rats. DESIGN: Open randomised study. SETTING: University
      departments of surgery and microbiology, Sweden. MATERIAL: 49 Sprague-Dawley
      rats. INTERVENTIONS: Rats were fed enterally for 7 days on diets supplemented
      with either glutamine or an isonitrogenous amount of non-essential amino acids.
      After feeding, 8 experimental and 8 control rats underwent sham operation; 9 and
      7, respectively, underwent moderate haemorrhage (to 65 mm Hg); and 9 and 8,
      respectively, underwent severe haemorrhage (50 mm Hg) without reinfusion. MAIN
      OUTCOME MEASURES: Microbiological analyses of samples of blood and mesenteric
      lymph nodes taken 24 hours after haemorrhage. RESULTS: The median (interquartile)
      number of colony forming units/mesenteric lymph nodes after moderate haemorrhage
      in animals who were given glutamine supplementation was 11 (0-34) and in control
      animals 20 (0-178). After severe haemorrhage the corresponding figures were 199
      (10-310) and 22 (0-187). No pathogens were isolated from blood cultures.
      CONCLUSION: Glutamine supplementation before haemorrhage did not reduce bacterial
      translocation to mesenteric lymph nodes in this rat model.

PMID- 7727604
TI  - Pancreatic cystadenoma and cystadenocarcinoma: diagnostic value of preoperative
      morphological investigations.
AB  - OBJECTIVE: To find out whether preoperative morphological investigations
      differentiated between serous cystadenoma, mucinous cystadenoma, and
      cystadenocarcinoma of the pancreas. DESIGN: Multicentre retrospective study of
      casenotes. SETTING: 24 Adult gastroenterology units (1 private, 8 non-university
      teaching hospitals, and 15 university teaching hospitals) in France. SUBJECTS: 71
      Patients with 74 tumours diagnosed between January 1978 and January 1988. MAIN
      OUTCOME MEASURES: Correlation between histological diagnosis and results of
      ultrasonography, computed tomography, angiography, and magnetic resonance
      imaging. RESULTS: 6 of 59 ultrasound scans (10%), 7 of 52 computed tomograms
      (13%), 0 of 18 angiograms, 1 of 12 pancreatograms (8%), and the single magnetic
      resonance scan correctly diagnosed the type of pancreatic tumour. Ultrasonography
      or computed tomography, or both, diagnosed cystadenoma (but not the type) in 26
      cases (37%). "Pseudocyst" was diagnosed in 14 cases (20%). CONCLUSIONS: In
      contrast to other studies, our results indicate that preoperative morphological
      investigations are of limited value in diagnosing cystadenomas of the pancreas.
      In particular, their ability to differentiate between different types of
      cystadenoma is poor.

PMID- 7727605
TI  - Sensitivity of interleukin-6 and C-reactive protein concentrations in the
      diagnosis of acute appendicitis.
AB  - OBJECTIVE: To evaluate the interleukin-6 (IL-6) concentration in the diagnosis of
      acute appendicitis, either as a single or four-hourly test. DESIGN: Open study.
      SETTING: Teaching hospital, Sweden. SUBJECTS: 165 consecutive patients admitted
      with suspected acute appendicitis. MAIN OUTCOME MEASURES: Correlation of
      concentrations of IL-6 and C-reactive protein with white cell count, duration of
      symptoms, and histological appearance of the appendix. RESULTS: Of 165 patients,
      101 patients had their appendices removed, and of these 86 had histologically
      confirmed appendicitis. An IL-6 concentration of less than 15 ng/l was accepted
      as the reference. On admission IL-6 concentrations above 15 ng/l gave a
      sensitivity of 66% and a specificity of 31% for acute appendicitis. Repeated
      tests were of no value. When the patients operated on were divided in groups
      depending on the duration of symptoms, C-reactive protein was the most valuable
      test after 24 hours' abdominal pain. Total white cell count has the most
      sensitive in patients with abdominal pain of less than 24 hours' duration.
      CONCLUSIONS: Measurement of IL-6 concentrations does not increase the accuracy of
      the diagnosis of acute appendicitis. There was no significant correlation between
      IL-6 and C-reactive protein concentrations.

PMID- 7727606
TI  - Modified vein cuff technique for distal polytetrafluoroethylene graft
      anastomoses: how we do it.

PMID- 7727607
TI  - Management of intermittent splenic torsion ("wandering spleen"): a review.

PMID- 7727608
TI  - Angiosarcoma associated with aneurysm of the popliteal artery.

PMID- 7727609
TI  - Isolated ileal perforation after minor blunt abdominal injury.

PMID- 7727610
TI  - Occlusion of the popliteal and tibial artery complicating multiple exostoses.

PMID- 7727611
TI  - Endothelin concentrations in experimental sepsis: profiles of big endothelin and
      endothelin 1-21 in lethal peritonitis in rats.
AB  - OBJECTIVE: To define the profiles of endothelin (ET), both big ET and active 21
      amino acid ET (ET 1-21) in the plasma and peritoneal cavity of rats with
      peritonitis. DESIGN: Open laboratory study. SETTING: University hospital, Norway.
      MATERIAL: 170 adult male Wistar rats. INTERVENTIONS: Lethal peritonitis was
      induced by making a 4 mm caecal perforation. MAIN OUTCOME MEASURES: Mortality,
      together with concentrations of total ET, ET 1-21 (measured by two
      radioimmunoassays), bacteria, endotoxin, tumor necrosis factor (TNF), interleukin
      6 (IL-6), and lactate at baseline, two hours, and then four-hourly intervals for
      24 hours. RESULTS: ET reached its maximum at 8 hours, and had returned to
      baseline after 24 hours. In the first phase of septicaemia there was more big ET
      than ET 1-21, but the proportions had equalised by 8 hours. There were higher
      concentrations of both big ET and ET 1-21 in peritoneal fluid than in plasma.
      CONCLUSIONS: In rats with peritonitis the profiles of big ET and ET 1-21 closely
      followed mortality, and blood concentrations of bacteria, endotoxin, TNF, IL-6,
      and lactate.

PMID- 7727612
TI  - Myoclonus associated with lorazepam therapy in very-low-birth-weight infants.
AB  - Lorazepam is being used with increasing frequency as a sedative in the newborn
      and the young infant. Concern has been raised with regard to the safety of
      lorazepam in this age group, especially in very-low-birth-weight (VLBW; < 1,500
      g) infants. Three young infants, all of birth weight < 1,500 g, experienced
      myoclonus following the intravenous administration of lorazepam. The potential
      neurotoxic effects of the drug (and its vehicle) in this population are
      discussed. Injectable lorazepam should be used with caution in VLBW infants.

PMID- 7727613
TI  - Hemodynamic interaction of chloralose pretreatment with subsequent beta
      adrenergic receptor antagonism in lambs.
AB  - alpha-Chloralose is a commonly used anesthetic agent in cardiovascular research
      despite a paucity of information whether it may have important pharmacologic
      interaction with subsequently given adrenergic drugs. To assess any potential
      pharmacologic interaction, we studied the cardiovascular response to beta
      adrenergic receptor antagonism (propranolol, 1 mg/kg i.v.) after either
      chloralose (30 mg/kg i.v.) or saline control in paired studies in 10 chronically
      instrumented neonatal lambs. Chloralose increased heart rate by 46% as compared
      to control (283 +/- 37 vs. 194 +/- 48 beats/min, p = 0.0002) and had no
      significant effect on cardiac output; chloralose also increased mean pulmonary
      arterial pressure by 45% (27 +/- 13 vs. 19 +/- 6 mm Hg, p = 0.050) and pulmonary
      vascular resistance by 79% (0.211 +/- 0.13 vs. 0.118 +/- 0.04 mm Hg/ml/kg/min, p
      = 0.050). The group pretreated with chloralose had significantly elevated heart
      rate (186 +/- 23 vs. 157 +/- 31 beats/min, p = 0.03), mean pulmonary arterial
      pressure (29 +/- 9 vs. 22 +/- 6 mm Hg, p = 0.03) and pulmonary vascular
      resistance (0.228 +/- 0.13 vs. 0.130 +/- 0.05 mm Hg/ml/kg/min, p = 0.05) after
      propranolol as compared to the conscious saline-treated group. We conclude that
      pretreatment with chloralose as an anesthetic agent may produce important
      pharmacologic interaction with subsequent adrenergic drugs in neonatal lambs.
      While anesthesia may be necessary in animal research, investigators should be
      aware that the anesthetic agent may also qualitatively and quantitatively
      influence measured outcome variables.

PMID- 7727614
TI  - Assessment of gut intraepithelial lymphocytes during late gestation and the
      neonatal period.
AB  - Intraepithelial lymphocyte counts (IEL % enterocytes) were carried out in
      histological samples of jejunal, ileal and appendiceal mucosa of 39 neonates,
      aged from birth to 28 days. Correlations between IEL counts and developmental
      factors, namely gestational age, birth weight and intrauterine growth, as well as
      neonatal infections or feeding state were performed. No significant differences
      were observed among neonates grouped according to birth weight, intrauterine
      growth or neonatal infections. The pattern of feeding, however was associated
      with significantly higher IEL counts (p < 0.02) in the ileum in oral/enterally
      fed neonates than in the unfed or parenterally fed. Full-term neonates also had
      higher counts in the ileum (p < 0.02). In this group, oral/enterally fed neonates
      had the higher values. Thus, besides in utero development, the pattern of feeding
      might be considered as an important modulating factor on IEL postnatal expansion.

PMID- 7727615
TI  - Developmental electrophysiology of encainide and its major metabolites on the
      Purkinje fiber action potential.
AB  - OBJECTIVE: With clinical data suggesting that neonates may be more prone to
      developing electrophysiologic side effects from encainide, this study
      investigates the in vitro developmental electrophysiologic effects of encainide
      and its major metabolites on the action potential parameters of the canine
      cardiac Purkinje fiber. METHODS: With standard microelectrode techniques, the in
      vitro tonic and rate-related effects of encainide, and its major metabolites (3
      methoxy-4-hydroxy encainide, MODE, and O-dimethyl encainide, ODE) were
      investigated using mature and immature canine cardiac Purkinje fibers. RESULTS:
      The significant developmental differences in the effects of these compounds on
      the canine Purkinje fiber illustrated in this study are: (1) 1 x 10(-6) M
      encainide depresses Vmax in neonatal Purkinje fibers, yet not in the adult. (2) 1
      x 10(-6) M MODE lengthens APD90 in the neonate, yet it has no substantial effect
      in the adult. (3) 1 x 10(-6) M ODE shortens APD90 in the adult, yet it has no
      appreciable effect on the neonate. (4) Rate-related effects of encainide and ODE
      are more pronounced in adult Purkinje fibers. CONCLUSION: In contrast to other in
      vitro studies on class I antiarrhythmic agents, neonatal canine Purkinje fibers
      seem to be more sensitive than the adult to the tonic depolarization depressant
      effect of encainide. This in vitro sensitivity parallels clinical experience with
      the drug in neonatal patients. Although encainide is no longer available for
      clinical use, these findings highlight the fact that the immature conduction
      system may show markedly different sensitivities to different class I agents
      despite the fact that these agents share similar qualitative pharmacologic
      properties.

PMID- 7727616
TI  - Prostaglandin E2 in cerebrospinal fluid of fetal and newborn sheep: central
      versus peripheral source.
AB  - During the perinatal period, prostaglandin (PG) E2 levels show parallel changes
      in cerebrospinal fluid (CSF) and blood which may be important for the adaptation
      of the fetus to extrauterine life. It is not known, however, whether PGE2 in the
      CSF originates from a local or a peripheral source. Experiments were carried out
      in term fetal and newborn sheep chronically instrumented with a cannula inside
      the third ventricle and vascular lines. Indomethacin was given
      intracerebroventricularly (i.c.v.) (50 or 100 micrograms at hourly intervals),
      alone or in combination with intravenous (i.v.) PGE2 (1 or 1.5
      micrograms/kg/min). In the fetus, i.c.v. indomethacin reduced PGE2 levels in both
      CSF and plasma. Conversely, no significant change was noted at either site when
      indomethacin was given i.c.v. to the newborn. At both ages, PGE2 increased in the
      CSF during i.v. infusion of the compound, but this elevation was proportionately
      smaller than in plasma. We conclude that, in the perinatal period, brain and
      peripheral circulation function as separate compartments with respect to PGE2,
      though there is passage of the compound across the blood-brain barrier. Results
      provide indirect evidence that perinatal brain produces PGE2 in measurable
      amounts.

PMID- 7727617
TI  - Effects of calcitriol on expression of triiodothyronine-stimulated renal tubular
      transport of p-aminohippurate in rats of different ages.
AB  - Following treatment of rats of various age groups with calcitriol (2
      micrograms/kg b.w., 3 days, once daily) renal tubular transport of p
      aminohippurate (PAH) is reduced in kidney cortical slices prepared from 5-, 15-,
      33-, and 55-day-old rats. The decrease in renal excretion of PAH following such
      treatment has a longer degree and is demonstrable in 15- and 33-day-old rats
      only. Repeated treatment with calcitriol provokes a decrease in body weight,
      statistically significant in 5- and 55-day-old rats. In 33- and 55-day-old rats
      repeated treatment with calcitriol (2 micrograms/kg b.w., 3 days, once daily)
      causes an increase of kidney weight. Repeated treatment with calcitriol is
      connected with an increase in plasma level and in renal excretion of calcium,
      statistically significant in most age groups. In rats of various age groups,
      renal tubular transport of PAH can be stimulated by repeated administration of
      triiodothyronine (T3; 100 micrograms/kg b.w., 3 days, once daily). This increase
      in PAH transport, measured in kidney cortical slices, cannot be observed in rats
      simultaneously treated with calcitriol and T3. Obviously, the expression of
      higher transport rates for PAH can be prevented by renal effects of calcitriol.
      Simultaneous treatment with T3 and calcitriol causes an increase in kidney weight
      and a decrease in body weight in rats of various age groups.

PMID- 7727618
TI  - Brain blood flow responses to indomethacin during hemorrhagic hypotension in
      newborn piglets.
AB  - Indomethacin has been shown to reduce cerebral blood flow and cerebral blood flow
      velocities in newborn infants and animals of various species. To answer the
      question of whether there may be a compromise of cerebral perfusion in
      hypotensive infants who have been treated with indomethacin, cerebral blood flow
      and cerebral vascular resistance were determined in 10 control and 16
      indomethacin-treated 1-day-old piglets during (1) steady state conditions; (2) 10
      min after the administration of saline or a 0.2-mg/kg dose of indomethacin; (3) 1
      h after saline or indomethacin administration, and (4) 10 min after induction of
      moderate hemorrhagic hypotension. Mean arterial blood pressures increased
      immediately after the infusion of indomethacin in the experimental group.
      Cerebral blood flows did not change throughout the study despite hemorrhagic
      hypotension in controls; cerebral blood flows were significantly decreased 10 min
      after indomethacin infusion in the experimental animals. However, total and
      regional cerebral blood flows were not further decreased in the presence of
      moderate hypotension. Cerebral vascular resistance increased 10 min after
      indomethacin infusion but returned to steady state 1 h following the indomethacin
      dose. These results suggest that indomethacin lowers baseline cerebral blood
      flow, but does not impair cerebrovascular regulatory responses during acute,
      moderate hemorrhagic hypotension in the newborn piglet.

PMID- 7727619
TI  - Effect of cyclooxygenase inhibition on brain cell membrane lipid peroxidation
      during hypoxia in newborn piglets.
AB  - To test the hypothesis that indomethacin, an inhibitor of cyclooxygenase, reduces
      free radical-induced brain cell membrane changes during cerebral hypoxia, we
      determined levels of brain cell membrane lipid peroxidation products and Na+,K(+)
      ATPase activity as indicators of free radical production and membrane function,
      respectively, in 29 newborn piglets divided into 4 groups. Eight saline- and 4
      indomethacin-treated normoxic animals served as controls; 8 saline-pretreated
      piglets and 9 piglets pretreated with indomethacin were exposed to hypoxic
      hypoxia for 60 min. Cerebral hypoxia was documented using 31P-NMR spectroscopy.
      In saline-pretreated hypoxic animals Na+,K(+)-ATPase activity decreased
      significantly and levels of membrane lipid peroxidation products increased
      significantly compared to normoxic controls. Indomethacin pretreatment prevented
      the hypoxia-induced increase in membrane lipid peroxidation products but had no
      effect on the decrease in Na+,K(+)-ATPase activity. Thus the apparent reduction
      in free radical production by indomethacin pretreatment did not prevent the
      hypoxia-induced change in Na+,K(+)-ATPase activity.

PMID- 7727620
TI  - Urinary N-acetyl-beta-D-glucosaminidase excretion in newborns.

PMID- 7727621
TI  - Imaging of human brain activation with functional MRI.

PMID- 7727622
TI  - Frontal brain volume and context effects in short-term recall in schizophrenia.
AB  - In a group of schizophrenic patients, magnetic resonance imaging (MRI) measures
      of relative frontal brain volume (total frontal volume/total cerebral volume)
      correlated highly with the capacity to use context as an aid to recall in a
      verbal memory task. The dorsolateral area of the prefrontal cortex appears to
      have contributed most to this effect. Recall of simple word lists without
      contextual features revealed no correlation with relative frontal volume. With
      increasing contextual organization of the material, correlations between frontal
      volume and recall scores increased significantly. These findings are consistent
      with the general proposition that impairment in the use of informational
      redundancy is a significant component of schizophrenic pathology.

PMID- 7727623
TI  - Subcortical hyperintensities on magnetic resonance imaging: clinical correlates
      and prognostic significance in patients with severe depression.
AB  - In 39 hospital inpatients with severe primary depressive disorders, we evaluated
      the relationships between subcortical hyperintensities on magnetic resonance
      imaging (MRI) and clinical features, neuropsychological impairment and response
      to standard therapies. Both white matter and gray nuclei lesions were associated
      with older age and the absence of a family history of affective disorder. White
      matter hyperintensities were also associated with onset of first affective
      episode after the age of 50 years and impaired psychomotor speed. Most
      importantly, the severity of white matter hyperintensities predicted a poorer
      response to treatment (r = -0.44, p < .01). Negative correlations of the same
      order were detected in those (n = 20) who received electroconvulsive therapy (r =
      -0.42, p = .06) and those (n = 19) who received pharmacotherapy alone (r = -.49,
      p < .05). This study provides preliminary evidence supporting the clinical and
      prognostic significance of extensive white matter hyperintensities in patients
      with severe depression.

PMID- 7727624
TI  - Brain hypometabolism of glucose in anorexia nervosa: a PET scan study.
AB  - Cerebral glucose metabolism was studied in 20 underweight anorectic girls and in
      10 age- and sex-matched healthy volunteers using positron emission tomography
      with (18-F)-fluorodeoxy-glucose. Both groups were scanned during rest, with eye
      closed and with low ambient noise. Compared to controls, the underweight
      anorectic group showed a global hypometabolism (p = .002) and an absolute (p <
      .001) as well as relative (p < .01) hypometabolism of glucose in cortical
      regions, with the most significant differences found in the frontal and the
      parietal cortices. Within the underweight anorectic and the control groups, no
      correlations were found between absolute or relative rCMRGlu and BMI, anxiety
      scores, or Hamilton scores of depression. Different factors might explain this
      reduction of glucose metabolism in anorexia nervosa. It might be the consequence
      of neurophysiological or morphological aspects of anorexia nervosa and/or the
      result of some associated symptoms such as anxiety or depressed feelings.
      Supported by cognitive studies, we can also hypothesize a primary corticocerebral
      dysfunctioning in anorexia nervosa.

PMID- 7727625
TI  - Choline ingestion increases the resonance of choline-containing compounds in
      human brain: an in vivo proton magnetic resonance study.
AB  - Choline is a crucial intermediate in several clinically relevant neurochemical
      processes. In this study, choline-containing compounds in human brain
      (principally phosphocholine, glycero-phosphocholine, and choline) were measured
      by 1H-magnetic resonance spectroscopy, before and after the ingestion of 50 mg/kg
      choline in four normal control subjects. Substantial and remarkably similar
      increases in the brain choline resonance occurred in each subject, with a nearly
      two-fold rise in the choline resonance observed 3 hr following choline ingestion
      (p = 0.008 versus baseline). One subject also received a dose of 200 mg/kg
      choline, and exhibited a proportionally larger increase in the brain choline
      resonance. The results are consistent with animal data reporting a rise in
      choline-containing compounds following choline administration. This is the first
      study to our knowledge where an oral nutrient has been shown to produce a
      detectable change in human brain composition in vivo. Studying choline transport
      and biotransformation in human brain may have relevance to several
      neuropsychiatric disorders, including affective disorders and dementia.

PMID- 7727627
TI  - Alcohol abuse and HIV infection have additive effects on frontal cortex function
      as measured by auditory evoked potential P3A latency.
AB  - Both alcohol and human immunodeficiency virus (HIV) infection have been shown to
      produce central nervous system (CNS) morbidity in frontal brain regions. The
      degree to which the CNS morbidity in HIV infection, as it affects frontal cortex
      function, may be preferentially increased by alcohol abuse was examined using the
      auditory P3A evoked potential. The P3A indexes an orienting response, maximal
      over frontal cortex that occurs when novel nontarget stimuli are presented in the
      midst of a target detection paradigm. Four groups of subjects were compared: HIV+
      alcohol abusers, HIV+ light/nondrinkers, HIV- alcohol abusers, and HIV-
      light/nondrinkers. The alcohol abuser and light/nondrinker HIV+ groups were
      matched on percent CD4 lymphocytes, insuring that the results reflected specific
      CNS effects and were not a result of differences between the groups in the degree
      of systemic immune suppression. Alcohol abuse and HIV infection had at least
      additive effects on P3A latency, consistent with alcohol abuse worsening the
      effect of HIV disease on frontal cortex function. Post-hoc analyses suggested
      that concomitant alcohol abuse results in the effects of HIV infection on P3A
      latency becoming manifest earlier in the HIV disease process.

PMID- 7727626
TI  - Age-related changes in [3H]GBR 12935 binding site density in the prefrontal
      cortex of controls and schizophrenics.
AB  - We investigated dopamine transporter receptor ligand binding in the prefrontal
      cortex as a function of age in schizophrenic and control postmortem brains.
      [3H]GBR 12935 binding constants were calculated by Scatchard analysis from the
      autopsied brains from 29 individuals with schizophrenia, and 28 control subjects.
      There were wide interindividual variations in Bmax and KD that were not related
      to gender, age, or postmortem interval (PMI) in controls. While there were no
      significant associations between gender, PMI, and Bmax, or KD in individuals with
      schizophrenia, there was a significant negative correlation between age and Bmax
      (r = -.44, p = .02). The slope of the regression lines between age and Bmax for
      the two groups was significantly different. The results suggest a differential
      effect of age, or something associated with age, on [3H]GBR 12935 binding sites
      in the prefrontal cortex of controls and individuals with schizophrenia.

PMID- 7727628
TI  - The thyroid, sleep, and depression.

PMID- 7727629
TI  - Influence of L-triiodothyronine on memory following repeated electroconvulsive
      shock in rats: implications for human electroconvulsive therapy.

PMID- 7727630
TI  - Pain thresholds in obese binge-eating disorder subjects.

PMID- 7727631
TI  - Absence of reduced platelet adenylate cyclase activity in Vietnam veterans with
      PTSD.

PMID- 7727632
TI  - No association between length of the (CAG)n repeat of the Huntington's disease
      gene and Tourette's syndrome.

PMID- 7727633
TI  - Escherichia coli O157:H7: clinical, diagnostic, and epidemiological aspects of
      human infection.
AB  - E. coli O157:H7 is one of many E. coli organisms that contain genes encoding one
      or more toxins similar in structure and function to Shiga toxin. E. coli O157:H7
      is the most frequently isolated diarrheagenic type of E. coli isolated in North
      America today; this pathogen can cause serious, even fatal disease. Syndromes
      caused by E. coli O157:H7 include diarrhea, hemorrhagic colitis, and HUS. Poorly
      cooked ground beef has been the most frequently implicated vehicle of
      transmission, but additional vehicles are being identified. Treatment consists of
      rehydration during hemorrhagic colitis and support of the patient during the
      multiple systemic complications of HUS. A policy of routine screening for E. coli
      O157:H7 in clinical microbiology laboratories, without reliance on the physician
      to request that this organism be sought or the technician to notice blood in the
      stool, is the most effective way to find cases. Timely and accurate diagnosis can
      prevent secondary transmission, avert unnecessary and possibly dangerous
      procedures and/or therapies, and detect continuing outbreaks. SLTEC strains other
      than E. coli O157:H7 may cause diseases similar to or less severe than those
      caused by E. coli O157:H7. At present, however, screening for such pathogens in
      clinical laboratories is too labor-intensive to be practical. Education and
      legislation should promote safe food-preparation and food-handling practices.
      Research should be directed at reducing the carriage of E. coli O157:H7 at its
      bovine source, minimizing the microbial content of food and water, and averting
      systemic microangiopathic hemolytic anemia after infection with this pathogen.

PMID- 7727634
TI  - Clinical and molecular epidemiology of Enterococcus faecalis bacteremia, with
      special reference to strains with high-level resistance to gentamicin.
AB  - The objective of this study was to characterize the clinical and molecular
      epidemiology of Enterococcus faecalis bacteremia, specifically that involving
      strains with high-level resistance to gentamicin (HLGR). Episodes of E. faecalis
      bacteremia at the Buffalo Veterans Affairs Medical Center from January 1986 to
      September 1989 were retrospectively identified. Of 94 episodes, 45 (48%) were due
      to strains with HLGR. Hemolytic activity was detected with greater frequency
      (85%) among the latter strains than among those without HLGR (P < .001). Of the
      54 episodes for which medical charts were available for review, 94% were hospital
      acquired, and 46% were due to strains with HLGR. An examination of the plasmid
      DNA content of isolates revealed restriction-fragment-length polymorphism. One
      plasmid pattern was identified in 15 isolates with HLGR (P < .001), and
      chromosomal DNA digest patterns suggested a common clonality; there was no direct
      evidence for patient-to-patient spread of these strains. The use of antibiotics,
      the presence of invasive devices, surgery, and admission to an intensive-care
      unit were not significantly associated with HLGR bacteremia. Mortality during
      hospitalization was 65%, with no difference between figures for HLGR and non-HLGR
      infections. This high mortality regardless of gentamicin susceptibility status
      suggests that E. faecalis bacteremia is a marker for severe illness. In contrast
      to previous studies, this investigation identified no clinical factors associated
      with HLGR E. faecalis bacteremia.

PMID- 7727635
TI  - Bacille Calmette-Guerin vaccines: a rough guide.

PMID- 7727636
TI  - Suppurative cutaneous granulomata caused by Microascus cinereus in a patient with
      chronic granulomatous disease.
AB  - We describe a patient with chronic granulomatous disease who presented with
      erythematous papular skin lesions on the chest, back, and arm. Examination of
      biopsy specimens from the lesions on the arm and back showed suppurative
      granulomata in association with acute and chronic inflammation. Histopathologic
      examination of a specimen from the lesion on the arm revealed fungal elements,
      and cultures yielded Microascus cinereus. The patient was treated with 2.5 g of
      intravenous amphotericin B, and the lesions resolved. We report what is, to our
      knowledge, the first case of invasive disease due solely to M. cinereus.

PMID- 7727637
TI  - Importance of Candida species other than C. albicans as pathogens in oncology
      patients.
AB  - A number of surveys have documented increased rates of candida infection over the
      past several decades. In this assessment of the frequency and distribution of non
      albicans Candida species among patients with cancer, 37 reports that were
      published between 1952 and 1992 and that described 1,591 cases of systemic
      candida infection were reviewed. Species other than Candida albicans accounted
      for 46% of all systemic candida infections in patients with cancer; specifically,
      Candida tropicalis accounted for 25%, Candida glabrata for 8%, Candida
      parapsilosis for 7%, and Candida krusei for 4%. Other species were uncommon. C.
      tropicalis was the predominant pathogenic Candida species in five reports, C.
      glabrata in two, C. krusei in two, and Candida stellatoidea in one. The
      perception that, over time, a greater proportion of candida infections have been
      caused by non-albicans species was not borne out. The wide variability in
      reported findings was striking and was due in part to differences in the
      underlying disease affecting the patients described. For example, patients with
      leukemia were more likely to be infected by C. albicans or C. tropicalis but less
      likely to be infected by C. glabrata than patients with other types of cancer.
      The recent increase in the rate of bone marrow transplantation may also have
      contributed to discrepancies among reports. Bone marrow transplant recipients
      were more likely to be infected by C. krusei or C. lusitaniae. The other factors
      partially responsible for the variability among reports included common-source
      contamination and the pressures imposed by antimicrobial measures.

PMID- 7727638
TI  - Relationship between bacille Calmette-Guerin (BCG) strains and the efficacy of
      BCG vaccine in the prevention of tuberculosis.
AB  - Bacille Calmette-Guerin (BCG) vaccination for the prevention of tuberculosis has
      been used in humans since 1921. Furthermore, for > 60 years it has been possible
      to separate BCG strains (defined here as a BCG vaccine maintained in a particular
      laboratory and used in a particular trial or set of trials) on the basis of in
      vitro and in vivo tests. Investigators have concluded that differences in the BCG
      strains used in efficacy trials on humans may be responsible for the wide range
      in levels of protection from tuberculosis reported in those trials. We review the
      development of the separate strains used in the trials included in a recent meta
      analysis and examine data for and against the protective efficacy of different
      BCG strains. The difficulties in correlating results of in vitro and in vivo
      tests with protective efficacy in humans are discussed. The limited data
      available from human studies suggest that the BCG strain used for vaccination is
      not a significant determinant of the overall efficacy in the prevention of
      tuberculosis.

PMID- 7727639
TI  - Bacille Calmette-Guerin vaccination for the prevention of tuberculosis in health
      care workers.
AB  - For 60 years vaccination with bacille Calmette-Guerin (BCG) has been used for the
      prevention of tuberculosis in health care workers. In 1988 the U.S. Advisory
      Committee on Immunization Practices removed the category of health care worker
      from the list of persons for whom vaccination with BCG should be considered.
      Nosocomial epidemics of tuberculosis, especially those caused by multidrug
      resistant strains, have led to the reconsideration of vaccination with BCG for
      this population. We review the available studies of the efficacy of BCG vaccine
      in health care workers. Although the studies had too many methodological flaws to
      be combined in a quantitative meta-analysis, they suggest that vaccination with
      BCG is effective in reducing the incidence of tuberculosis among health care
      workers.

PMID- 7727640
TI  - Adjunctive therapy for septic shock: a review of experimental approaches.
AB  - Septic shock remains a major cause of morbidity and mortality, especially in the
      intensive care setting. A vast array of treatment strategies is under
      investigation; despite success in animal models, no effective adjunctive therapy
      has yet been approved for clinical use. This paper reviews the development of
      experimental therapies for sepsis and discusses those treatments that show
      promise for application in humans. Approaches to treatment fall into three broad
      categories: strategies directed against bacterial components, those directed
      against host-derived inflammatory mediators, and those designed to limit tissue
      damage. Because septic shock is a dynamic and evolving condition, different
      strategies may be needed at different stages in the pathogenesis of sepsis.
      Through carefully performed trials and thoughtful selection of combination
      therapy aimed at different points in the pathological process, it may be possible
      in the future to modify the course of this serious condition.

PMID- 7727641
TI  - Photo quiz. Bacillary angiomatosis.

PMID- 7727642
TI  - Hospital-acquired infectious endocarditis not associated with cardiac surgery: an
      emerging problem.
AB  - To assess the most relevant features of hospital-acquired endocarditis, we
      conducted a retrospective study of cases of infectious endocarditis at a single
      university hospital from 1978 through 1992. During this period 248 episodes of
      infectious endocarditis were documented; 23 (9.3%) of these episodes were
      hospital-acquired and were not associated with cardiac surgery. (This figure
      represented a remarkable rise in the frequency of nosocomial endocarditis, only
      one case of which was identified among 101 cases of endocarditis treated at the
      same institution between 1960 and 1975.) In each of the 23 nosocomial cases,
      endocarditis was the result of bacteremia associated with a hospital-based
      procedure: intravenous catheterization (15 cases), instrumentation of a diseased
      urogenital tract (seven cases), or liver biopsy (one case). Staphylococcus aureus
      and Enterococcus faecalis were the predominant organisms isolated from
      intravenous catheters and the urogenital tract, respectively. Two of seven
      enterococcal isolates were highly resistant to gentamicin (MIC, > 2,000
      micrograms/mL). Overall mortality was 56%. Two subsets of at-risk patients with
      different anatomic and clinical manifestations were identified. Our results
      emphasize that infectious endocarditis must be considered a serious nosocomial
      hazard against which preventive measures must be implemented.

PMID- 7727643
TI  - Elevated serum antibody response to toxin A following splenic abscess due to
      Clostridium difficile.
AB  - Splenic abscess and segmental small-bowel infarction were documented in a patient
      from whose splenic culture Clostridium difficile was isolated. A week and a half
      after splenectomy and partial bowel resection, diarrhea developed and stool
      cultures yielded an isolate of C. difficile that was identical to the abscess
      isolate when subjected to restriction endonuclease analysis. The level of IgG
      antibody to toxin A was markedly higher in serum from this patient than in sera
      from patients with C. difficile diarrhea alone. This case illustrates a rare but
      serious extraintestinal manifestation of infection with C. difficile and suggests
      a correlation between serum levels of IgG antibody to toxin A and systemic
      exposure to C. difficile, a typically noninvasive enteric pathogen.

PMID- 7727644
TI  - Acute invasive rhinocerebral zygomycosis in an otherwise healthy patient: case
      report and review.
AB  - A previously healthy 19-year-old man developed rapidly progressive invasive
      rhinocerebral zygomycosis due to Apophysomyces elegans. He required extensive
      surgery and prolonged treatment with high-dose i.v. amphotericin B for cure. This
      is only the third reported case of acute invasive rhinocerebral zygomycosis in an
      otherwise healthy patient and the first reported case of infection due to A.
      elegans in any patient. We review the literature and clinical spectrum of
      rhinocerebral zygomycosis in otherwise healthy patients and discuss the recently
      recognized association between A. elegans and zygomycosis in immunocompetent
      patients.

PMID- 7727645
TI  - Rhodococcus meningitis in an immunocompetent host.
AB  - Rhodococcus species are increasingly being recognized as pathogens, especially in
      patients infected with the human immunodeficiency virus. Most cases of
      rhodococcus infection in these patients are due to Rhodococcus equi and involve
      the lungs. CNS infections due to Rhodococcus species are rare, and meningitis due
      to non-equi Rhodococcus has never been reported in a healthy host. We report a
      case of meningitis due to non-equi Rhodococcus in a previously healthy 24-year
      old woman. We also review and summarize the reported cases of CNS infections
      caused by Rhodococcus species.

PMID- 7727646
TI  - Infection due to parvovirus B19 in patients infected with human immunodeficiency
      virus.
AB  - Parvovirus B19 has been described as a cause of chronic anemia in
      immunosuppressed patients, including those infected with human immunodeficiency
      virus (HIV). In this study serological assays and the polymerase chain reaction
      (PCR) were used to establish the prevalence of both prior and active infection
      due to parvovirus B19 among a general population of 105 HIV-infected individuals
      (cohort I) and among 22 HIV-infected patients with anemia (cohort II). Eight
      individuals in cohort I (7.6%) had IgG antibodies to parvovirus B19, while none
      had B19-specific IgM antibodies. In cohort II, four patients (18.2%) had B19
      specific IgG antibodies and none had IgM antibodies. Only one person in cohort I
      (0.95%) and one person in cohort II (4.5%) had evidence on PCR of persistent
      infection with parvovirus B19; both of these patients lacked IgG and IgM
      antibodies to parvovirus. Both individuals with B19 viremia were anemic and had
      CD4 lymphocyte counts suggesting advanced immunosuppression (< 50/mm3). The
      observed low prevalences of B19 seropositivity and active B19 infection differ
      from the rates documented in previous studies and indicate that infection with
      parvovirus B19 is uncommon in some groups of HIV-infected patients.

PMID- 7727647
TI  - Relapse of tularemia after aminoglycoside therapy: case report and discussion of
      therapeutic options.
AB  - We describe a patient with ulceroglandular tularemia who initially responded to
      therapy with gentamicin but then clinically relapsed. Ciprofloxacin was
      subsequently given for 28 days, and the patient was clinically cured.
      Aminoglycosides have been considered the drugs of choice in the treatment of
      tularemia; however, potential alternative treatments do exist. We review the
      English-language literature on this topic.

PMID- 7727648
TI  - Fatal disseminated infection due to Exserohilum rostratum in a patient with
      aplastic anemia: case report and review.
AB  - Exserohilum rostratum is a dematiaceous fungus that rarely causes infection in
      humans. We describe a patient with severe aplastic anemia who developed fatal
      disseminated disease caused by E. rostratum, and we review the English-language
      literature on this unusual agent. Our patient initially presented with signs and
      symptoms of sinusitis, which progressed to invasive pulmonary disease. The
      clinical course and histopathologic findings at autopsy were similar to those
      seen in cases of invasive aspergillosis or mucormycosis in that a propensity for
      vascular invasion and dissemination was seen.

PMID- 7727649
TI  - Postulates for the evaluation of adverse reactions to drugs.
AB  - In most large clinical trials, any unexplained adverse event that occurs during
      the administration of the study drug is considered to be possibly drug-related.
      While this approach is effective in identifying the adverse effects of a drug, it
      does not take into account other, non-drug-related factors that may have caused
      the event. In very few of these clinical trials has there been an attempt to
      validate that these events are actually drug-induced; yet, they might still be
      reported as a side effect in the leaflet insert when the drug is later marketed.
      When such adverse events are erroneously attributed to drug toxicity, allergy, or
      idiosyncrasy, it could affect the clinician's decision to use that drug. Some
      patients may therefore be deprived of a valuable therapeutic tool. Certain
      postulates should be answered before an adverse effect is considered to be drug
      related. It should also be determined whether or not a reaction is due to drug
      toxicity rather than to allergy or idiosyncrasy. While all adverse events cannot
      be put to the same stringent tests, under reasonable and safe circumstances, such
      practices will allow for a more accurate evaluation of a drug and its suspected
      adverse effects.

PMID- 7727650
TI  - Yeast in the urine: solutions for a budding problem.
AB  - The significance of candiduria ranges from simple procurement-related
      contamination to disseminated candidiasis. Ensuring that a valid urine specimen
      is collected and carefully assessing patients for risk factors predisposing to
      disseminated candidiasis permit the stratification of cases into three clinical
      categories: (1) asymptomatic candiduria in a previously healthy patient; (2)
      candiduria in a high-risk patient in whom disseminated candidiasis is unlikely;
      and (3) candiduria in a high-risk patient with a potential for disseminated
      candidiasis. Strategies for management are tailored to the individual patient.
      Appropriate management of anatomic genitourinary abnormalities and removal of
      bladder catheters may result in the resolution of candiduria, although some
      patients require systemic antifungal therapy. All patients with candiduria should
      be evaluated for evidence of deep-seated tissue infection or candidemia before
      therapy is instituted. Fluconazole appears to be a safe and effective agent for
      the management of candidal urinary tract infection. Both its safety and its ease
      of administration make it superior to amphotericin B for this purpose.

PMID- 7727651
TI  - Difficulties in diagnosing gonococcemia.

PMID- 7727652
TI  - Efficacy of liposomal amphotericin B in the treatment of visceral leishmaniasis
      in patients coinfected with the human immunodeficiency virus.

PMID- 7727653
TI  - Pneumonia, pericarditis, and endocarditis in a child with Corynebacterium xerosis
      septicemia.

PMID- 7727654
TI  - Bordetella bronchiseptica infection in patients with AIDS.

PMID- 7727655
TI  - Functional asplenia and pneumococcal sepsis in patients with systemic lupus
      erythematosus.

PMID- 7727656
TI  - Acute suppurative Salmonella enteritidis thyroiditis associated with
      thyrotoxicosis in a patient infected with the human immunodeficiency virus.

PMID- 7727657
TI  - Invasive Acremonium falciforme infection in a patient with severe combined
      immunodeficiency.

PMID- 7727658
TI  - Pancreatic abscess due to Eikenella corrodens in association with severe
      ethanolism.

PMID- 7727659
TI  - Lyme borreliosis in a patient with severe multiple cranial neuropathy.

PMID- 7727660
TI  - Use of diclazuril for the treatment of isosporiasis in patients with AIDS.

PMID- 7727661
TI  - Purulent pericarditis due to Clostridium septicum associated with carcinoma of
      the colon.

PMID- 7727662
TI  - Atypical lymphocytosis in babesiosis.

PMID- 7727663
TI  - Community-acquired pneumonia due to Acinetobacter lwoffii in a patient infected
      with the human immunodeficiency virus.

PMID- 7727664
TI  - Myelitis due to varicella-zoster virus in an immunocompromised patient without a
      cutaneous rash.

PMID- 7727665
TI  - Persistence of a multiresistant clone of Staphylococcus epidermidis in a neonatal
      intensive-care unit for a four-year period.
AB  - A cluster of cases of Staphylococcus epidermidis bacteremia in a neonatal
      intensive-care unit (NICU) during 1991 raised the question of whether these
      infections were caused by a single strain. Sixty-seven isolates of S. epidermidis
      from blood cultures of 56 neonates treated in the NICU between 1986 and 1992 and
      54 control strains from other patients with bacteremia were characterized by
      three typing methods: antibiogram, plasmid profile, and ribotype. Plasmid
      profiles and ribotype patterns indicated that 11 (16%) of the 67 episodes of S.
      epidermidis bacteremia in the NICU were caused by a single strain. Although this
      epidemic strain did not account entirely for the increase in the incidence of
      bacteremia in the NICU, it did persist for 4 years during the study period. Other
      clones responsible for smaller outbreaks were also found. These results suggest
      that S. epidermidis cross-infections are very common in the NICU setting.

PMID- 7727666
TI  - The reporting of communicable diseases: a controlled study of Neisseria
      meningitidis and Haemophilus influenzae infections.
AB  - Surveillance systems for communicable diseases in the United States are primarily
      passive. We compared the passive reporting system for invasive disease caused by
      Neisseria meningitidis and Haemophilus influenzae with a concurrent, active
      laboratory-based system in the four metropolitan counties of Tennessee. The
      passive reporting system identified approximately 50% of all cases that were
      identified by the active system and accurately reflected trends in disease
      occurrence during the study period. Of all reported cases, physicians contributed
      fewer than 4%. Nearly 40% of all hospitals in the study area did not participate
      in the passive system. This lack of participation resulted in disproportionately
      increased reporting of disease among blacks. Inconsistencies in case definition
      within the state also contributed substantially to underreporting and lack of
      demographic representativeness of reported cases. The median reporting interval
      (the time from the onset of disease to transmission of the case report to the
      Centers for Disease Control and Prevention) was 24 days (range, 5-157 days).
      Efforts to improve surveillance of those infections for which isolation of a
      pathogen is tantamount to a diagnosis should concentrate on laboratory-based
      reporting and the use of currently available computer telecommunication systems.

PMID- 7727667
TI  - Corynebacterium pseudodiphtheriticum: a respiratory tract pathogen in adults.
AB  - Corynebacterium pseudodiphtheriticum has been reported to be an uncommon
      respiratory pathogen. We describe the clinical and microbiologic features of 17
      patients from whose sputum C. pseudodiphtheriticum was isolated. Patients were
      identified through a review of the reports from the clinical microbiology
      laboratory at York Hospital, a community teaching hospital, from October 1990
      through April 1993; 17 patients with respiratory infection caused by C.
      pseudodiphthriticum were identified. There were 12 cases of bronchitis and five
      of pneumonia. An underlying systemic condition, particularly congestive heart
      failure, chronic obstructive pulmonary disease, diabetes mellitus, or malignancy,
      was common. Onset of symptomatology was acute for most patients, but fever was
      noticeably absent in almost two-thirds of the cases. Isolates were uniformly
      susceptible to the beta-lactam antibiotics, vancomycin, and trimethoprim
      sulfamethoxazole, but resistance to clindamycin and erythromycin was common. The
      isolation of diphtheroids from a properly obtained sputum sample from a patient
      with respiratory tract infection should not always be dismissed as due to
      contamination. The isolation, identification, and susceptibility testing of C.
      pseudodiphtheriticum from respiratory tract specimens may provide information
      useful for treatment of patients.

PMID- 7727668
TI  - Corynebacterium pseudodiphtheriticum: a respiratory tract pathogen.
AB  - From January 1986 through February 1993, there were 16 episodes of respiratory
      infection due to Corynebacterium pseudodiphtheriticum in 13 patients. The ages of
      patients ranged from 24 to 77 years; the ratio of male to female patients was
      3:1. One patient had three episodes of infection, and another patient had two. In
      one patient, who died of disseminated intravascular coagulation, the level of IgG
      was low. One patient was receiving prednisolone when the infection occurred. In
      two cases a mixed infection with Streptococcus pneumoniae was noted. Sputum
      cultures yielded C. pseudodiphtheriticum (> or = 10(7) cfu/mL). An increased
      neutrophil response in the sputum of infected patients was observed. Gram
      staining and electron microscopy of sputum showed phagocytosis of C.
      pseudodiphtheriticum by the neutrophils. ELISAs also showed an increase in the
      level of immunoglobulin against C. pseudodiphtheriticum after infection. Tests
      for determination of MICs of antibiotics revealed that C. pseudodiphtheriticum
      isolates were susceptible to ampicillin, amoxycillin/clavulanic acid, cefazolin,
      cefuroxime, ceftazidime, and imipenem. All strains were resistant to nalidixic
      acid; borderline susceptibility to ofloxacin, norfloxacin, and ciprofloxacin was
      noted. We suggest the use of beta-lactam antibiotics in the treatment of
      infection with C. pseudodiphtheriticum.

PMID- 7727669
TI  - Successful treatment of New World cutaneous leishmaniasis with a combination of
      topical paromomycin/methylbenzethonium chloride and injectable meglumine
      antimonate.
AB  - Colombian patients with New World cutaneous leishmaniasis were treated with a
      combination of a topical formulation (15% paromomycin sulfate/5%
      methylbenzethonium chloride, twice a day) and parenteral meglumine antimonate (20
      mg of antimony [Sb]/kg.d]). Cohort 1 received topical therapy for 10 days and Sb
      for 7 days; 18 (90%) of the 20 patients were cured (follow-up, 12 months). Other
      clinical data suggested that neither the topical formulation alone nor the 7-day
      regimen of Sb alone would have cured many patients. In a subsequent cohort, which
      received topical therapy for 10 days and Sb for 3 days, the cure rate was 42%
      (eight of 19 patients). In Colombian cohorts (historical controls) treated with
      Sb alone for 10-15 days, the cure rate was 31%-36%. Side effects in cohort 1
      patients consisted of local reactions to the topical formulation: burning and
      pruritus in 25% of patients and vesicle formation in 15% of patients. This is the
      first report that a regimen partially composed of topical antimicrobial agents
      can be highly effective for treatment of New World cutaneous leishmaniasis.

PMID- 7727670
TI  - Congenital cytomegalovirus infection in offspring of liver transplant recipients.
AB  - There has been an increasing number of women undergoing liver transplantation
      during their childbearing years. As the number of pregnancies among these women
      increases, complications during pregnancy and risks to the fetus associated with
      liver transplantation will be better defined. We report three cases of
      cytomegalovirus (CMV) infection in offspring of liver transplant recipients. Two
      of these recipients had preterm labor and gave birth at approximately 23 weeks'
      gestation; both neonates had clinical (hydrops fetalis), laboratory, and
      placental evidence of CMV infection. The third recipient gave birth at 26 weeks'
      gestation because of severe preeclampsia, and the neonate died at 12 days of age
      of CMV sepsis. Placental CMV infection was confirmed in this case by polymerase
      chain reaction analysis, which is a valuable tool for prospectively or
      retrospectively diagnosing this infection. Our findings indicate that CMV
      infection poses a significant risk to offspring of liver transplant recipients.

PMID- 7727671
TI  - Randomized comparison of cefepime and ceftazidime for treatment of hospitalized
      patients with gram-negative bacteremia.
AB  - We conducted a randomized, prospective, open comparison to evaluate the efficacy
      and safety of cefepime and ceftazidime in the treatment of hospitalized patients
      with suspected gram-negative bacteremia. Twenty-eight patients with signs and
      symptoms of sepsis were prospectively randomized to receive cefepime (13
      patients) or ceftazidime (15 patients). Cultures of blood obtained at entry into
      the study were positive for 24 (85.7%) of 28 patients. Eight patients had two or
      more positive pretreatment blood cultures, and the remaining 16 had one positive
      pretreatment blood culture. The most commonly isolated blood pathogen was
      Escherichia coli. Eleven of 13 patients treated with cefepime and 12 of 15
      patients treated with ceftazidime were clinically cured. Adverse effects
      attributable to therapy with the study drugs were minimal in both groups of
      patients and included rash, headache, nausea, and diarrhea. Our results suggest
      that cefepime is an efficacious and well tolerated as is ceftazidime in the
      treatment of hospitalized patients with documented gram-negative bacteremia.

PMID- 7727672
TI  - Fatal human pulmonary infection caused by an Angiostrongylus-like nematode.
AB  - An immunocompetent man developed malaise, fever, progressive weight loss,
      eosinophilia, and transient pulmonary infiltrates that responded to steroid
      treatment but recurred after its discontinuation. Examinations of feces,
      bronchoalveolar lavage fluid, and pulmonary tissue obtained during a 50-day
      period of hospitalization yielded negative results. When a new bronchoalveolar
      lavage sample and a new pulmonary biopsy specimen showed nematode larvae and
      adult worms, treatment with thiabendazole was started. However, therapy with this
      agent and then with mebendazole had no impact on the patient's downhill course,
      which ended in respiratory distress and death. Autopsy documented an overwhelming
      pulmonary infection with a metastrongylid nematode resembling a species of
      Angiostrongylus. Histologic study revealed features of necrotizing angiitis
      closely mimicking those of Wegener's granulomatosis. To our knowledge, this is
      the first reported instance of patent metastrongylid parasitism of the human
      pulmonary arteries with necrotizing angiitis caused by a reaction to the parasite
      and/or its metabolic products.

PMID- 7727673
TI  - An epidemic of food-borne listeriosis in western Switzerland: description of 57
      cases involving adults.
AB  - This article describes 57 cases of listeriosis that occurred in adults in western
      Switzerland during an outbreak associated with the consumption of a soft cheese.
      Twenty-one percent of the cases were of bacteremia, 40% were of meningitis, and
      39% were of meningoencephalitis. Overall, 42% of the patients had an underlying
      disease and 54% were > 65 years of age. Patients with bacteremia were
      significantly older than those with meningitis or meningoencephalitis (median
      ages, 75, 69, and 55 years, respectively). The epidemic strain, defined by phage
      typing, was isolated in three-quarters of the listerial cases observed during the
      epidemic period and did not appear to differ significantly from the nonepidemic
      strains in terms of virulence. The overall mortality associated with the 57 cases
      was 32%. Among the patients' characteristics, age and type of clinical
      presentation were independent predictors of death in a multivariate logistic
      regression model (pseudo-r2 [coefficient of determination], .26; both P values <
      .05), and a presentation of meningoencephalitis was associated with an increased
      death risk (odds ratio, 6.5; 95% confidence interval, 1.1-39.5; P < .05).
      Neurological sequelae developed in 30% of the survivors of CNS listeriosis.

PMID- 7727674
TI  - Isolation of nontuberculous, non-avium mycobacteria from patients infected with
      human immunodeficiency virus.
AB  - Mycobacterium avium serovars account for 97% of typeable M. avium complex (MAC)
      organisms causing infection in patients with AIDS. We reviewed 216 consecutive
      cultures that yielded nontuberculous mycobacteria (NTM) from 212 patients. Only
      the first isolate of each species of NTM recovered from each patient was analyzed
      in the study. Among the 92 patients infected with the human immunodeficiency
      virus, 96 NTM organisms were identified; M. avium was recovered from 50 (77%) of
      the 65 NTM-positive cultures of blood or bone marrow, while Mycobacterium
      intracellular and other non-avium NTM accounted for 18% and 5% of the isolates,
      respectively. Little difference in the susceptibility of isolates to antibiotics
      was noted between HIV-positive and HIV-negative patients or between M. avium and
      M. intracellulare. These data demonstrate that HIV-positive patients develop
      disseminated disease with NTM other than M. avium more frequently than has been
      previously reported and that these patients do not appear to be infected with NTM
      that are more resistant to antimicrobial agents than are NTM isolated from HIV
      negative patients.

PMID- 7727675
TI  - Isolation of fluconazole-resistant Candida albicans from human immunodeficiency
      virus-negative patients never treated with azoles.
AB  - Isolation of fluconazole-resistant strains of Candida species from human
      immunodeficiency virus (HIV)-infected patients after repeated or continuous
      courses of treatment has been reported with increasing frequency. During 1991
      1992, MICs of fluconazole for 139 Candida albicans isolates from our institution
      were bimodally distributed: 102 strains were susceptible (MICs, < or = 4
      micrograms/mL) and 37 were resistant (MICs, > or = 8 micrograms/mL). There was
      incomplete cross-resistance between fluconazole and ketoconazole or miconazole,
      and there was no cross-resistance between azoles and amphotericin B or
      flucytosine. Twenty of the 37 fluconazole-resistant strains were isolated from 17
      HIV-negative patients, some with systemic infections, who had never been treated
      with azoles. There were no differences in characteristics or risk factors for
      those patients as compared with those for an equal number of HIV-negative
      patients from whom fluconazole-susceptible strains were isolated. Among patients
      with systemic infection, 6 (50%) of 12 with infection caused by fluconazole
      resistant strains survived and 11 (69%) of 16 with infection caused by
      fluconazole-susceptible strains survived (P = .54). Survival was not found to be
      related to treatment regimen, but the number of patients was small. The emergence
      of fluconazole-resistant C. albicans among HIV-negative patients never exposed to
      azoles is of concern.

PMID- 7727676
TI  - Molecular epidemiology of infections due to Enterobacter aerogenes:
      identification of hospital outbreak-associated strains by molecular techniques.
AB  - Molecular techniques were used to study the epidemiology of infections due to
      Enterobacter aerogenes in a tertiary-care hospital. Sixty-two clinical isolates
      were collected from 43 patients over 3 months. Restriction endonuclease analysis
      (REA) of chromosomal DNA and repetitive-element polymerase chain reaction (rep
      PCR) with primers based on repetitive extragenic palindromic (REP) and
      enterobacterial repetitive intergenic consensus (ERIC) bacterial DNA sequences
      were used for genomic fingerprinting. REA with HindIII or EcoRI yielded complex
      banding patterns that differentiated community-acquired from some hospital
      acquired organisms. Less complex fingerprints were obtained with rep-PCR, which
      also distinguished between epidemiologically unrelated strains. More
      discriminatory DNA fingerprints were provided by rep-PCR when REP primers rather
      than ERIC primers were used. Two clusters of genomically distinct isolates from
      patients with recent or current exposure to the hospital environment were
      identified by REA and rep-PCR. Most isolates within each cluster contained
      characteristic plasmids, and some isolates contained additional plasmids. These
      results suggest colonization and infection with genotypically related strains of
      E. aerogenes in a nosocomial setting. Although REA and plasmid profiling are
      useful techniques for the epidemiological typing of E. aerogenes, genomic
      fingerprinting with rep-PCR may offer the advantages of ease, speed, and broad
      species applicability over existing molecular-typing techniques.

PMID- 7727677
TI  - Persistent and relapsing infections associated with small-colony variants of
      Staphylococcus aureus.
AB  - Small-colony variants (SCVs) of Staphylococcus aureus were cultured from five
      patients with persistent and relapsing infections. All five SCV strains were
      nonhemolytic and nonpigmented and grew very slowly on routine culture media in an
      ambient atmosphere. In several instances, these phenotypic characteristics led to
      the initial misidentification of the organisms in the clinical microbiology
      laboratory. All four strains available for further analysis were shown to be
      auxotrophs that reverted to normal growth and morphology in the presence of
      menadione, hemin, and/or a CO2 supplement. Similarly, these isolates were
      resistant to aminoglycosides under routine conditions but susceptible in the
      presence of the metabolic supplements. For two patients, the large and small
      colony forms isolated concurrently were indistinguishable when analyzed by pulsed
      field gel electrophoresis and thus represented phenotypic variants within
      individual clones. We propose a model relating the phenotypic characteristics of
      S. aureus SCVs with the clinical pattern of persistent and relapsing infection.

PMID- 7727678
TI  - Synthesis and binding properties of several new dopaminergic ligands.
AB  - Four different heterocyclic dopamine bioisosteres were synthesized. The affinity
      and selectivity of these compounds for the D-1 and D-2 classes of the dopamine
      receptor were determined in competition binding experiments using synaptosomal
      membranes from bovine caudate nuclei and [3H]SCH 23390 (D-1 selective) and
      [3H]spiperone (D-2 selective) as radioligands. None of these compounds expressed
      significant affinity for the D-1 receptors, while compounds 3, 4, 2 and 1 in this
      order of potency strongly competed with [3H]spiperone binding to D-2 receptors
      under conditions that prevented radioligand binding to serotonin 5HT2 receptors
      (50 nM ketanserin). Compounds 3 and 4 behave as agonists as judged by the data
      obtained in competition binding experiments in the presence of Gpp(NH)p, the
      former (3) expressing a very high affinity for D-2 receptors.

PMID- 7727679
TI  - Predicting the brain-penetrating capability of histaminergic compounds.
AB  - Recently published data on histaminergic H1-receptor agonists are used to
      evaluate two models for predicting brain penetration. The physicochemical model
      of Young et al., using the parameter delta log P (the difference between the
      measured partition coefficients log octanol/water and log cyclohexane/water) is
      found to overestimate the brain penetration of the agonists by factors of 2-5. A
      theoretical model of van de Waterbeemd and Kansy, using the calculated parameters
      VM (molar volume) and SP (polar surface area) is found to overestimate the brain
      penetration by even larger factors.

PMID- 7727680
TI  - Homology modelling of the dihydrofolate reductase-thymidylate synthase
      bifunctional enzyme of Leishmania major, a potential target for rational drug
      design in leishmaniasis.
AB  - A homology model of the dimeric Leishmania major dihydrofolate reductase
      thymidylate synthase bifunctional enzyme was built based upon the available
      crystallographic structures of the dihydrofolate reductase and thymidylate
      synthase monofunctional enzymes. The corresponding substrates, cofactors and
      inhibitors of the monofunctional enzymes were modelled in the active-sites of the
      homodimeric model of the bifunctional enzyme. The small number of residues in the
      interdomain region of the L. major sequence, compared to the other DHFR-TS
      sequences, imposed severe constraints on the relative locations of the two
      functional domains. The DHFR and TS domains in the malarial, trypanosomal and
      toxoplasmia structures are likely to have comparable locations. The leishmanial
      model reveals features which may be of use in designing novel antifolates for
      leishmaniasis and protozoal parasites in general.

PMID- 7727681
TI  - Structure-based drug design: inhibitors of purine nucleoside phosphorylase.
      Index: structure-based drug design: inhibitors of PNP.

PMID- 7727682
TI  - Synthesis and benzodiazepine receptor activity of some 4,5-dihydro-1H
      pyrazolo[4,3-c][1,8]naphthyridine derivatives.
AB  - The preparation of 5-substituted 1-aryl-4,5-dihydro-1H-pyrazolo[4,3- c][1,8]
      naphthyridines by reaction of 5-substituted 3-hydroxymethylene-2,3-dihydro-1,8
      naphthyridin-4(1H)-ones with various phenylhydrazines is described. The
      benzodiazepine binding activity of these compounds was evaluated in vitro. Only
      the 5-methyl substituted derivatives showed affinity for the benzodiazepine
      receptor, with K1 values ranging from 2.9 to 0.195 microM for the para-phenyl
      substituted compounds. A hypothesis of interaction of these ligands with the
      receptor site is reported.

PMID- 7727683
TI  - Synthesis of new derivatives of flavone-8-acetic acid.
AB  - The synthesis of new flavone-8-acetic acid derivatives is described. It is
      studied the influence of a dialkylaminomethyl group in the 3-position on the
      activity. None of the new compounds showed cytostatic activity.

PMID- 7727684
TI  - To Sheldon M. Wolff, as we commemorate the 10th anniversary of the clonings of IL
      1 alpha and IL-1 beta.

PMID- 7727685
TI  - The biological properties of interleukin-1.
AB  - Interleukin-1 (IL-1) is primarily an inflammatory cytokine. Biologically, IL-1 is
      more closely related to tumor necrosis factor (TNF) than any other cytokine or
      interleukin, although the structure and receptors for IL-1 and TNF are clearly
      distinct. IL-1 is active in the low pM and fM range and IL-1 receptors (IL-1R)
      are expressed in most cells, although less than 100 receptors per cell is not an
      uncommon finding. Based on short-term blockade of IL-1 receptors in humans and
      animals and IL-1 beta knock-out mice, there is no evidence that IL-1 beta plays a
      role in development, or normal homeostasis such as metabolism, hematopoiesis,
      renal and hepatic function or regulation of blood pressure. On the other hand, IL
      1 alpha is found constitutively produced by various epithelial cells,
      keratinocytes of the skin and in the brain. In these locations, IL-1 may
      contribute to cell growth and repair functions. During inflammation, injury,
      immunological challenge or infection, IL-1 is produced and because of its
      multiple biological properties, IL-1 must contribute to disease. Most studies on
      IL-1 are derived from experiments in which humans or animals are injected with IL
      1 or IL-1 is added to cells in vitro. The biological properties of IL-1 suggest
      that its effects often mimic host responses to infection, inflammation, injury or
      immunologic challenge. Using specific IL-1 blockade, it is clear IL-1 is playing
      a critical role in some disease processes. This review will focus on IL-1 as a
      cytokine of primary and strategic importance to the initiation and progression of
      inflammatory and infectious diseases.

PMID- 7727686
TI  - Molecular studies on interleukin-1 alpha.
AB  - When rabbit alveolar macrophages were treated with phorbol-12-myristate-13
      acetate (PMA) and lipopolysaccharide (LPS), the synthesis of interleukin-1 (IL
      1), as well as tumor necrosis factor (TNF), was greatly increased. These
      inducible cytokines were subjected to cloning by the differential colony
      hybridization method and the subsequent mRNA hybridization-translation assay.
      Cloned rabbit IL-1 cDNA was disclosed to encode the sequence of the counterpart
      of the mouse IL-1 alpha. This cDNA was used as a hybridization probe to screen a
      human cDNA library which was constructed from induced HL-60 cells, a human
      promyelocytic leukemia cell line. Isolated human IL-1 alpha cDNA was shown to
      direct the synthesis of a polypeptide with IL-1 activity in E. coli expression
      system. The chromosomal gene for human IL-1 alpha was isolated and characterized
      to elucidate the structural organization of this gene. To identify the region
      that is essential for regulating IL-1 alpha gene expression, various CAT
      (chloramphenicol acetyltransferase) fusion plasmids were constructed and analysed
      for their ability to direct CAT synthesis in a transient expression system. The
      unpublished results obtained in the early stages of these experiments are also
      presented and discussed in this review.

PMID- 7727687
TI  - Interleukin-1 receptors.

PMID- 7727688
TI  - Interleukin-1 signal transduction.

PMID- 7727689
TI  - Interleukin-1, tumor necrosis factor and their specific inhibitors.
AB  - It has become evident during the past years that interleukin-1 (IL-1) and tumor
      necrosis factor alpha (TNF-alpha), mainly produced by monocyte-macrophages, are
      the principal mediators of tissue destruction in many immuno-inflammatory
      diseases such as rheumatoid arthritis (RA). However, the discovery of a
      biologically active monokine of approximately 17 kD preceded the isolation of IL
      1 and TNF-alpha as well as their cloning by more than 16 years. The two latter
      cytokines induce in synergy the production of high levels of matrix
      metalloproteinases (MMP) by fibroblasts, synovial cells and chondrocytes. The
      biological activity of MMP is controlled by tissue inhibitor of MMP (TIMP) which
      also depends on the presence of cytokines in the microenvironment. One of the
      principal stimuli of the production of IL-1 and TNF-alpha is the direct contact
      between the membranes of activated lymphocytes and monocyte-macrophages. Several
      glycoproteins expressed on the surface of activated lymphocytes (CD11, CD69) are
      implicated in this activation process and can be partially blocked by their
      respective antibodies. These prompt the decrease of cytokines and proteases in
      the lymphocyte/monocyte interaction. In the past few years, two pathways for
      inhibiting the activation of macrophages, fibroblasts and synovial cells have
      been elucidated. One of them is due to the action of anti-inflammatory cytokines
      such as IL-4 and IL-10 which considerably decrease production of IL-1, TNF-alpha
      and metalloproteases. In contrast to IL-4, IL-10 is also capable of stimulating
      the production of TIMP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727690
TI  - Interleukin-1: a gene expression system regulated at multiple levels.

PMID- 7727691
TI  - Interleukin-13 gene expression by malignant and EBV-transformed human B
      lymphocytes.
AB  - Expression of the IL-13 gene in malignant tissues from 26 human B-cell lymphoid
      malignancies was analyzed by reverse transcriptase-polymerase chain reaction (RT
      PCR). A positive signal was detected in 16 cases, which included high grade B
      lymphomas, follicular lymphomas and B-cell chronic lymphocytic leukemias. IL-13
      mRNA was also detected in the 9 malignant B cell lines and in the 6
      lymphoblastoid cell lines tested, as well as in freshly isolated malignant B
      cells from 2 patients with a Burkitt's lymphoma. Two of 8 T-cell lymphomas and 2
      of 4 T-cell lines expressed the IL-13 gene. In contrast, IL-13 gene expression
      was not detected in any of the 5 non-lymphoid cell lines tested. No specific
      binding of radiolabeled IL-13 was detected on B cell lines, suggesting an absence
      of IL-13 receptors on such cells. This conclusion was also supported by the
      inability of IL-13 or anti-IL-13 antibodies to affect the growth of malignant B
      cells. Taken together, these results show that both malignant and EBV-transformed
      B lymphocytes, either freshly isolated or maintained as cell lines, express the
      IL-13 gene. This raises the question of the role of B lymphocyte-derived IL-13, a
      B lymphocyte stimulating cytokine, on the in vivo function of normal B
      lymphocytes as well as on the in vivo behaviour of B lymphoid malignancies.

PMID- 7727692
TI  - Hans J. Bremermann: a pioneer in mathematical biology.

PMID- 7727693
TI  - Characterization of prediction in the primate visual smooth pursuit system.
AB  - To define predictive behavior and mechanisms in visual smooth pursuit, various
      target motions were presented to 2 monkeys. Target stimuli included: single
      sinusoids (1's), triangle waves (T's), sums of 4 nonharmonically related
      sinusoids (4's), bandpass limited white noise (B's), and wideband white noise
      (N's). Velocity error was least for 1's, greatest for N's, and intermediate for
      T's, 4's, and B's. For the bandlimited 4's and B's, monkeys demonstrated the
      greatest relative amplitude response at the highest frequencies. Predictive
      mechanisms are classified as short- and long-term, depending on how much past
      target motion information is employed. The T's and a modification of this
      stimulus pattern involving a random perturbation were used to test the hypothesis
      that prediction is based exclusively on short-term signal processing related to
      target position and its derivatives. The existence of long-term predictive
      mechanisms in monkey smooth pursuit was unequivocally demonstrated with the use
      of the latter stimulus.

PMID- 7727694
TI  - Elements of a systematic search in animal behavior and model simulations.
AB  - Starting from a position paper by Hans Bremermann, general aspects of search
      behavior are envisaged: locomotion itself, the capability of orientation and
      possible storage of information about the 'goals' of a search. The importance of
      stochasticity in these processes is briefly discussed. In particular,
      experimental findings and theoretical concepts on the homing search of desert
      isopods (Hemilepistus reaumuri) are presented. Using the general framework of
      stochastic differential equations for the angular turning rate of a migrating
      individual, search paths with characteristic loops and meanders can be modelled
      and simulated. Search success is quantified by measuring the degree of path
      overlap and by computing an index of area search intensity. Quantities are
      plotted versus path length, both for observed isopod data and for typical
      simulated search paths. Certain elements of a systematic search are described and
      explained by a hypothesis about temporal locomotion control, based on the
      isopod's ability for path integration and directional compensation. Finally,
      possible effects of orientational cues are mentioned.

PMID- 7727695
TI  - Parameter identification of a neurological control model for the pathological
      head movements of cerebellar patients.
AB  - The objective of this research is to explore the role of the cerebellum in the
      human motor control system. The present study quantitatively compares the
      neurological control signals effecting fast, horizontal head rotations in normal
      subjects to those in patients with a cerebellar lesion. The method involves the
      use of a computer simulation model for one degree-of-freedom movements. A method
      for unconstrained global optimization, first proposed by Hans Bremermann (1970),
      is used to identify the timing and magnitudes of the input neurological control
      signals to the model, which are compared to recorded electromyograms (EMGs).
      Experimentally recorded kinematics from cerebellar patients and from normal
      subjects were used to drive the parameter search. These simulations found that
      cerebellar patients' neurological control signals were altered with respect to
      those of normal subjects, and suggest that the electromyographic activity of
      cerebellar patients may comprise at least five bursts of activity whereas normal
      subjects typically exhibit only three. The results are discussed with respect to
      the hypothesis that the cerebellum may be involved in both the timing and
      magnitudes of the neurological control signals effecting voluntary movement.

PMID- 7727696
TI  - The role of dehydro-alanine in the design of peptides.
AB  - X-ray crystallography, NMR spectroscopy and theoretical studies on some
      oligopeptides containing dehydro-alanine (delta Ala) have indicated that delta
      Ala adopts an extended conformation and also induces a definite conformation in
      the preceding saturated residue. In order to evaluate the conformational
      constraints imposed by delta Ala on the neighbouring saturated residues, we have
      undertaken a systematic, theoretical study of the preferred conformations of
      tripeptide sequences of the type N-Ac-X-delta Ala-NHCH3 and N-Ac-delta Ala-X
      NHCH3 (X = Gly, L-Ala, L-Val, L-Ile and L-Phe). The methodology and parameters
      used have been standardized against sequences with known crystal structures. The
      significant findings of this study are that delta Ala always adopts an extended
      conformation and induces in both the preceding and the succeeding neighbouring
      saturated residues a conformation in which phi approximately 140 degrees and psi
      approximately -40 degrees. These results have a direct application in the design
      of peptide sequences for specific biological activity.

PMID- 7727697
TI  - Constantly 'awake' brain and Bremermann's question.

PMID- 7727698
TI  - Evolutionary credit apportionment and its application to time-dependent neural
      processing.
AB  - A new approach to training recurrent neural networks is applied to temporal
      neural processing problems. Our method combines Darwinian variation and selection
      with a credit apportionment mechanism for assigning credit to individual neurons
      within the groups of competing networks. Interconnections between the networks
      allow the outputs of neurons in one network to be available to the neurons in
      other networks. The firing behavior of the neurons in a variety of networks is
      compared with the corresponding neurons in high performing networks for specific
      input contexts. Payoffs accorded to neurons in one network can thus be shared
      with neurons in other networks. Only the best neurons over the entire repertoire
      of networks are allowed to pass their crucial function-determining parameters on
      to other neurons. The algorithm is demonstrated with connectionist-type units on
      several temporal processing tasks and compared to genetic algorithms.

PMID- 7727699
TI  - Computing with dynamic attractors in neural networks.
AB  - In this paper we report on some new architectures for neural computation,
      motivated in part by biological considerations. One of our goals is to
      demonstrate that it is just as easy for a neural net to compute with arbitrary
      attractors--oscillatory or chaotic--as with the more usual asymptotically stable
      fixed points. The advantages (if any) of such architectures are currently being
      investigated; but it seems reasonable that the much richer dynamics of recurrent
      networks, so obvious in recordings of brain activity, must be useful for
      something. On the other hand, the constraints of computing with biological wet
      ware may make chaotic dynamics unavoidable in complex nervous systems. We
      hypothesize also that the as yet unrivaled capabilities of the human brain derive
      from an ability to integrate both analog intuitive pattern recognition
      operations, and digital symbolic logical operations at the ground level of its
      hardware. To investigate these possibilities, we have constructed a parallel
      distributed processing architecture inspired by the structure and dynamics of
      cerebral cortex. The construction assumes that cortex is a set of coupled
      associative memories with dynamic attractors. It is guided also by a particular
      concept of the physical structure required of macroscopic computational systems
      in general for reliable computation in the presence of noise. Our challenge is to
      accomplish real tasks that brains can do, using ordinary differential equations,
      in networks that are as faithful as possible to the known anatomy and dynamics of
      cortex.

PMID- 7727700
TI  - A shape representation for computer vision based on differential topology.
AB  - We describe a shape representation for use in computer vision, after a brief
      review of shape representation and object recognition in general. Our shape
      representation is based on graph structures derived from level sets whose
      characteristics are understood from differential topology, particularly
      singularity theory. This leads to a representation which is both stable and whose
      changes under deformation are simple. The latter allows smoothing in the
      representation domain ('symbolic smoothing'), which in turn can be used for
      coarse-to-fine strategies, or as a discrete analog of scale space. Essentially
      the same representation applies to an object embedded in 3-dimensional space as
      to one in the plane, and likewise for a 3D object and its silhouette. We suggest
      how this can be used for recognition.

PMID- 7727701
TI  - A precondition prover for analogy.
AB  - We describe here a prover PC (precondition) that normally acts as an ordinary
      theorem prover, but which returns a 'precondition' when it is unable to prove the
      given formula. If F is the formula attempted to be proved and PC returns the
      precondition Q, then (Q-->F) is a theorem (that PC can prove). This prover, PC,
      uses a proof-plan. In its simplest mode, when there is no proof-plan, it acts
      like ordinary abduction. We show here how this method can be used to derive
      certain proofs by analogy. To do this, it uses a proof-plan from a given guiding
      proof to help construct the proof of a similar theorem, by 'debugging'
      (automatically) that proof-plan. We show here the analogy proofs of a few simple
      example theorems and one hard pair, Ex4 and Ex4L. The given proof-plan for Ex4 is
      used by the system to prove automatically Ex4; and that same proof-plan is then
      used to prove Ex4L, during which the proof-plan is 'debugged' (automatically).
      These two examples are similar to two other, more difficult, theorems from the
      theory of resolution, namely GCR (the ground completeness of resolution) and GCLR
      (the ground completeness of lock resolution). GCR and GCLR have also been
      handled, in essence, by this system but not completed in all their details.

PMID- 7727702
TI  - Wavelet variations on the Shannon sampling theorem.
AB  - The Shannon sampling theorem asserts that a continuous square-integrable function
      on the real line which has a compactly supported Fourier transform is uniquely
      determined by its restriction to a uniform lattice of points whose density is
      determined by the support of the Fourier transform. This result can be extended
      to the wavelet representation of functions in two ways. First, under the same
      type of conditions as for the Shannon theorem, the scaling coefficients of a
      wavelet expansion will determine uniquely the given square-integrable function.
      Secondly, for a more general function, there is a unique extension from a given
      set of scaling coefficients to a full wavelet expansion which minimizes the local
      obstructions to translation invariance in a variational sense.

PMID- 7727703
TI  - Analytic representation of compactly supported wavelets.

PMID- 7727704
TI  - Partitioning non-linearities in the response of honey bee olfactory receptor
      neurons to binary odors.
AB  - In many organisms, of which honey bees are one example, a general (i.e., non
      pheromonal) olfactory receptor neuron may respond to some odorants by increasing
      its firing rate and to others by decreasing its firing rate. In the latter case,
      this decrease will be with respect to a background firing rate determined by
      intrinsic (internal noise) and extrinsic (background odors) factors. To analyse
      receptor neurons of this complexity, we extend Beidler's model of receptor
      protein activation dynamics to account for the competition between depolarizing
      and hyperpolarizing pathways and couple the model to a phenomenological
      description of the non-linear relationship between the proportion of activate
      membrane receptors and the receptor cell spike generation rates. We then examine
      the implications of this theory for predicting the response of receptor neurons
      to odor mixtures based on their response to pure odorants at concentrations
      matched to the mixture. We derive inequalities that must be satisfied under our
      normative model, and propose that deviations from the model be designated as
      synergisms and inhibitions, depending on the direction in which various
      equalities and inequalities are violated. We then apply our inequalities to
      identifying synergisms and inhibitions in data analysed in a different way
      elsewhere (Akers, R.P. and Getz, W.M. Response of olfactory receptor neurons in
      honey bees to odorants and their binary mixtures. J. Comp. Physiol. (in press)).
      In these data regarding the response of honey bee placode sensilla to a number of
      odorants and their binary combinations, we demonstrate the presence of synergisms
      and inhibitions--that is, elevated or repressed responses that are not due to
      competitive interactions of mixture component odorants for receptor sites or
      Beidler (Beidler, L.M., 1962. Taste receptor stimulation. Prog. Biophys. Biophys.
      Chem. 12, 107-151) saturation mechanisms.

PMID- 7727705
TI  - Return to equilibrium--or why we may be losing information from our physiologic
      experiments.
AB  - Many times when we conduct experiments, we often forget that after the system is
      perturbed, it usually returns to an equilibrium state, and analysing the manner
      in which it returns may yield information about the system. In this paper, I
      illustrate this fact by examining two different biomedical systems.

PMID- 7727706
TI  - Network thermodynamics revisited.
AB  - Modeling provides a bridge between the natural sciences (physics, chemistry,
      biology, and the like) and the axiomatic sciences (mathematics and statistics).
      Inductively-derived descriptive models map observations of physical processes
      into mathematical descriptions that can be treated as axioms (e.g., the various
      laws of physics). A synthetic model combines descriptive models of several
      physical processes with a structural model (representing the interactions of
      those processes) for the purpose of deducing or predicting the consequences of
      interactions. When applied together with elementary thermodynamic principles,
      circuit theory provides an excellent framework for synthetic modeling.

PMID- 7727707
TI  - Intercellular signaling in neuronal-glial networks.
AB  - Glial cells have recently been found to exhibit electrophysiological and
      metabolic responses to many neurotransmitters and neuromodulators. These findings
      have focused attention on the possibility that active signaling between neurons
      and glia could represent an important form of intercellular communication within
      the brain. Since glial and neuronal networks are both physically and
      metabolically interlinked, such intercellular signaling may represent a mechanism
      for inducing collective changes in the cellular physiology of neuronal and glial
      cell populations. Within the nervous tissue of both vertebrate and invertebrate
      organisms, glial cells are known to secrete extracellular signal molecules,
      modulate carbohydrate metabolism, and control the volume and ionic composition of
      extracellular space. In this paper, the roles that cytoplasmic [Ca2+] transients
      may play in regulating these glial cell functions are reviewed. Mechanisms by
      which intracellular Ca oscillations and intercellular Ca waves may be generated
      in neurotransmitter-stimulated glial cells are also discussed. In addition, it is
      proposed that rhythmic glial cell contractions and shape changes, which have been
      observed for many decades, are linked to Ca-induced secretion of ions, water, and
      neuroactive compounds. These activities represent mechanisms by which Ca-induced
      changes in glial cell physiology could potentially alter the excitability of
      neuronal networks.

PMID- 7727708
TI  - On the maternal transmission of immunity: a 'molecular attention' hypothesis.
AB  - Maternally-derived antibodies can provide passive protection to their offspring.
      More subtle phenomena associated with maternal antibodies concern their influence
      in shaping the immune repertoire and priming the neonatal immune response. These
      phenomena suggest that maternal antibodies play a role in the education of the
      neonatal immune system. The educational effects are thought to be mediated by
      idiotypic interactions among antibodies and B cells in the context of an
      idiotypic network. This paper proposes that maternal antibodies trigger localized
      idiotypic network activity that serves to amplify and translate information
      concerning the molecular shapes of potential antigens. The triggering molecular
      signals are contained in the binding regions of the antibody molecules. These
      antibodies form complexes and are taken up by antigen presenting cells or
      retained by follicular dendritic cells and thereby incorporated into more
      traditional cellular immune memory mechanisms. This mechanism for maternal
      transmission of immunity is termed the molecular attention hypothesis and is
      contrasted to the dynamic memory hypothesis. Experiments are proposed that may
      help indicate which models are more appropriate and will further our
      understanding of these intriguing natural phenomena. Finally, analogies are drawn
      to attention in neural systems.

PMID- 7727709
TI  - Cancer: causes, prevention, control and treatment (introduction).
AB  - Growth is one of the most complicated phenomena of life in its heterogeneity
      composed of the cooperation of myriads of single processes. This is exemplified
      by the realization that there exists not one cause of cancer but several groups
      often ethnically influenced. Species-specific variations occur during the
      neoplastic development, which exhibits two main phases: I. The change of body
      metabolism leading via the malignant transformation to a primary tumor; II. The
      further progression of the neoplastic disease. This introduction, as a brief
      review, deals with the first phase of neoplastic development examining as
      causative factors, environment and diet on a comparative approach; to this first
      phase also belong the cancer causing therapies of nonneoplastic diseases.

PMID- 7727710
TI  - The clinical use of multimodality therapy in the management of cancer.
AB  - The essential challenge in managing malignant disease with intent of cure is to
      eradicate the last malignant cell without imposing unacceptable burdens regarding
      toxicity, functional loss, or damaged cosmesis. In this review we examine the
      strengths and limitations of surgery, radiotherapy, and systemic chemotherapy
      when used as single modalities and the unique features of each that allow their
      advantageous combination. Finally, we consider newer developments in the
      antineoplastic armamentarium which may soon contribute to the challenges of
      achieving cure with acceptable sequelae.

PMID- 7727711
TI  - Bio-immunotherapy for cancer in experimental studies and clinical application:
      current status and future challenges.
AB  - Although successful treatment of patients with primary tumor by conventional
      surgery and radiotherapy is often possible, death frequently results from tumor
      metastases. Since metastasis has already occurred in many cancer patients at the
      time of diagnosis, a major emphasis of cancer treatment is and will continue to
      be the prevention or successful management of tumor metastases. Systemic
      chemotherapy has been widely used in the past in the hope of preventing or
      controlling micrometastases. The results of this treatment have been
      disappointing with little impact on survival in the vast majority of solid
      tumors. Bio-immunotherapy has emerged as another modality and is finding
      acceptance and use in treating patients with cancer. The role of bio
      immunotherapy in traditional surgery, radiotherapy, chemotherapy and hyperthermia
      will be discussed. In order to evaluate new and innovative treatments, we and
      others have used murine models of erythroleukemia and solid tumors with
      metastatic potential to assess the effects in vivo of bio-immunotherapy. Tumor
      metastases can be dampened and immunosuppression restored by bio-immunotherapy,
      especially when used in combination with other forms of treatment. Most of the
      combination treatments used in animal models are encouraging but are by no means
      totally adequate or curative yet. The molecular basis of cancer is now understood
      to involve activation of dominant oncogenes and inactivation of tumor suppressor
      genes. These genetic events may represent novel targets for cancer treatment. The
      potential use and ethical implications of gene transfer to alter the behavior of
      somatic cells in patients with cancer has been noted. Also reported is genetic
      immunomodulation by introducting genes for cytokines into tumor cells or
      lymphocytes to stimulate a cytotoxic immune response against the tumor. As with
      bone marrow, human cord blood can be used for transplantation in the autologous,
      related allogeneic and unrelated allogeneic settings, and as a target cell for
      gene treatment. It is believed that the greatest therapeutic results of bio
      immunotherapy, including biological response modifiers, cytokines, gene treatment
      and bone marrow transplantation, will come in combination with other established
      effective modalities including surgery, radiation treatment, chemotherapy and
      hyperthermia in the treatment of patients with cancer.

PMID- 7727712
TI  - Relation of apoptosis to cancer therapy.
AB  - Apoptosis, or programmed cell death, is a mode of cell death characterized by
      distinctive biochemical and morphological features that include endonuclease
      activation, chromatin condensation and margination, and cellular shrinkage and
      fragmentation. Its role is homeostatic regulation essential in the maintenance of
      renewable tissues; the process is controlled by the interaction of genes and
      tissue-specific hormones or growth factors. A number of apoptosis-regulating
      genes have recently been discovered including bc1-2, c-myc, and p53. Recent
      experimental evidence suggests that apoptosis plays an important role in
      regulation of tumor growth and tumor response to various forms of cancer therapy,
      including radiotherapy and chemotherapy. Apoptosis develops rapidly, within
      hours, after cytotoxic treatments and is dose dependent. The apoptotic response
      correlates well with the antitumor efficacy of radiation and chemotherapy, which
      makes it a candidate predictor of tumor treatment response. Tumors vary in their
      apoptotic response to cytotoxic agents, with carcinomas being more responsive
      than sarcomas. In addition to this intertumor heterogeneity, there is also
      significant intratumor heterogeneity in apoptosis induction, consistent with the
      idea that the propensity for apoptosis is genetically regulated. Regulating
      apoptosis might be an effective way to improve tumor therapy; therapeutic gain
      would be achieved by increasing apoptotic response of tumors or by inhibiting
      apoptotic response of normal tissues.

PMID- 7727713
TI  - The combination of stem cell transplantation and immunotherapy: future potential.
AB  - In summary, a number of new immunotherapeutic strategies are being developed to
      take advantage of the reduced tumor burden that occurs following induction
      chemotherapy and stem cell transplantation. Novel strategies to accelerate
      hematopoietic reconstitution have become accepted and/or are rapidly being
      implemented. These include the use of PBSC's as compared to BM stem cells. PBSC's
      appear to accelerate hematopoietic reconstitution, have a lower likelihood of
      occult tumor cell contamination and contain a greater number of T cells in the
      product which may allow an accelerated immunologic reconstitution post
      transplantation. Similarly, the concept of GVT is no longer viewed as an
      epiphenomenon but following allotransplantation is an objectively supported and
      clinically important phenomena. Further, post transplantation adjunct therapy
      with a variety of immunoaugmenting agents may induce an autologous GVT response.
      Additional benefits of PBSCT beyond those associated with the accelerated
      hematopoietic reconstitution and concomitant tumor reduction is the reduced
      expense of transplantation due to a shorter stay within the hospital. The
      isolation of stem cells (CD-34+) with or without ex vivo expansion to reduce the
      amount of stem cell product required is also an exciting new clinical strategy.
      This approach may also reduce the tumor cell contamination of the stem cell
      product, result in a more rapid hematologic reconstitution and reduce costs.
      However, it also has a potential down side due to a reduced infusion of mature
      and functional T cells. The comparison of PBSC to BM for transplantation of NHL
      suggests that the infusion of, or rapid reconstitution of, a functional immune
      system may have therapeutic benefit as discussed above. Thus, in addition to
      strategies based on the induction of an autologous GVT there is the need to
      develop/initiate clinic strategies to overcome the immunosuppression-anergy
      associated with stem cell transplantation, as well as, augment tumor specific T
      cell responses to "mop up" the residual tumor cells post transplantation. Clearly
      the clinical use of cytokines, especially in conjunction with PBSCT, has as a
      goal not only the reduction of morbidity and mortality associated with standard
      therapy but also dose intensification and scheduled compression so that
      increasing numbers of individuals may survive their current neoplasia. However,
      to date the use of the ex vivo expansion of stem and progenitor cells remains a
      largely unexplored clinical application for use in transplantation.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7727714
TI  - The influence of microenvironmental factors during cancer therapy.
AB  - The response of tumour cells to chemotherapy or radiotherapy is clearly dependent
      upon the inherent sensitivity of the cells to those agents. That sensitivity can,
      however, be markedly affected by the biochemical and physiological status of the
      tumour cell during treatment. In this review, a critique of the current evidence
      for, and the extent of, microenvironmental heterogeneity in tumours is presented.
      Its influence on radiation and chemotherapy is then examined, with examples from
      the author's studies with spheroids in vitro, and xenografted human tumours in
      vivo. In conclusion, new therapeutic strategies for which the tumour
      microenvironment is an asset (as opposed to a liability) are explored.

PMID- 7727716
TI  - Applications of diagnostic radiology to radiation oncology.
AB  - Despite advances in oncology, the local control of malignancies remains a
      formidable challenge. For the radiation oncologist, this challenge is approached
      by greater precision in the definition of the tumor and normal tissue with the
      intent of encompassing the former and excluding the latter from the high dose
      volume of treatment. Advances in diagnostic imaging have been incorporated into
      radiation therapy planning to achieve this goal. Recent developments in three
      dimensional treatment planning of CNS and pelvic malignancies illustrate the
      extent to which radiation oncology has come to rely on diagnostic imaging and the
      promise it offers for improvement in clinical care.

PMID- 7727715
TI  - Carcinoma of the vocal cord. Results after subperichondral cordectomy.
AB  - The clinical outcome of 110 patients operated upon by subperichondral cordectomy
      between 1982 and 1992 for T1s/T1a, NO, MO carcinomas of the vocal cord has been
      evaluated in this longitudinal epidemiological study. Patients have been followed
      up until the end of 1993 by examinations done once a month (first year), every
      three months (years 2 to 4), every six months (years 5 to 8), and then once a
      year. Life-tables have been computed according to Kaplan and Meier and raw
      survival has been 90.0%. Considering only the mortality due to any type of
      neoplastic disease, the survival reached 93.6%. Finally, considering only deaths
      due to recurrences or metastases of the primary tumor, the survival rate was
      95.5%. Mortality after the first recurrence was 27.3%, after a second recurrence
      50.0%. A correlation between number of cigarettes smoked and the risk of
      recurrence of the tumor could be observed (p < 0.01), while gross appearance and
      histologic grading of the vocal cord carcinoma proved to be uncorrelated with the
      risk of recurrences.

PMID- 7727717
TI  - Cancer prevention clinical trials.
AB  - Many kinds of cancer are preventable. Avoidance of tobacco would essentially
      eliminate lung cancer and most head and neck cancers as well. Other common
      cancers (breast, colon, prostate) are related to diet and therefore may also be
      preventable, at least in part. Abundant epidemiologic and laboratory data link
      specific nutrients including fat, fiber and vitamins to cancer so that
      appropriate manipulation of these constituents might reduce cancer risk.
      Determination of appropriate manipulations requires prospective clinical trials
      in humans. Approximately 40 such trials are in progress. Some have been completed
      with encouraging results. Future large scale trials will require designs that
      overcome the barriers of cost, large subject numbers and long study duration. The
      use of "intermediate markers" rather than cancer end points is a strategy that
      will help overcome these barriers.

PMID- 7727718
TI  - Treatment of circulating neoplastic cells.
AB  - The differentiation of tissues and organs during ontogeny increases the necessity
      of integration of the different structures. These developmental processes of
      integrations by body fluids, immunologic, endocrine and nervous systems culminate
      in mammals, since they possess the most diversified system of body fluids.
      Typical of the most developed mammals are the bone marrow, the lymphatic system
      with regional lymph nodes and consequently the pathologic development of the
      diversity of leukemias, malignancies without stroma. In the German literature the
      leukemias are considered systemic diseases because the floating cells they
      discharge are more or less uniformly pathologically underdeveloped. The leukemias
      are named according to the major abnormal cell type (e.g. monocytic acute
      leukemia). Acute and chronic is the distinction of the time limitation regarding
      the development and duration of the disease. More complicated is the discharge of
      motile cells from primary tumors or daughter tumors deriving from solid tumors.
      These motile cells enter into the circulation via the lymphatic spaces or by
      penetration of the endothelium of the blood vessels. They move freely in the
      circulatory system until settling in a more or less distant region. The process
      of detecting these cells is known as carcinocythemia. Other movable cells during
      neoplastic progression are those populating effusions in the coelomic cavities.
      Non-movable, that is only growing in succession like a tissue chain are those
      tumors which distribute by direct tumor spread within the veins, keeping the
      connection with the primary tumor. This condition is especially well-known in
      renal cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727719
TI  - Cancer related syndromes from a comparative viewpoint.
AB  - Neoplasms are the most prominent portion of the neoplastic disease process. The
      cancer patient is affected by hormonal, metabolic, immunologic and paraneoplastic
      discrepancies. Paraneoplastic syndromes consist a large group of body
      abnormalities which appear in a specific manner. Why special components of such
      abnormalities occur together is nearly always unknown. This article gives a
      tabulation of the paraneoplastic and other neoplasia-related syndromes providing
      certain key characteristics in each case.

PMID- 7727720
TI  - Hodgkin's disease: treatment and secondary neoplasms.
AB  - Hodgkin's disease is a lymphoma which occurs in man in the lymph nodes or in
      extra-lymphatic tissue. The disease was first described in 1832 by Thomas
      Hodgkin, a British physician. The disease develops with different patterns of
      histology in several types which a varying degree of malignancy: stages of the
      disease processes may be encountered. Lymph nodes appear phylogenetically first
      in the mesentery of crocodiles and reach the top of their development in the
      mammal. Here they are important during the neoplastic development as regional
      stations thereof. The treatment, depending on the cellular make-up of the type,
      may vary from advantageous to very toxic. Successful treatment in several cases
      on the one hand, in contrast to high therapeutic toxicity, and the development of
      secondary neoplasms on the other, are outlined.

PMID- 7727721
TI  - Treatment considerations for older patients with cancer.
AB  - It is apparent that cancer is primarily a burden for geriatric populations. This
      conclusion is based both upon the greater incidence of the disease with advancing
      age and the increasing distribution of elderly people in western cultures. Three
      questions have arisen that form the underpinnings of the evolving subspecialty of
      geriatric oncology. These are: Why are tumors more frequent in the elderly? Is
      there a difference in tumor aggressiveness with advancing age? And, should
      treatment be different for the older patient? Experimental data and clinical
      experience have indicated that tumors are not resistant to treatment by virtue of
      age alone. However, age is associated with slight reductions in certain organ
      functions, and these deficiencies might be magnified by comorbid conditions.
      Cancer treatments, especially chemotherapy may therefore be more toxic and
      therefore treatment should be tailored for the individual taking into
      consideration potential increased toxicities balanced by patients expectations.
      Quality of life considerations assume even greater importance in geriatric
      populations.

PMID- 7727722
TI  - Retinoids, gap junctional communication and suppression of epithelial tumors.
AB  - There is increasing evidence that gap junctional communication plays an important
      role in the control of morphogenesis, differentiation and growth. Here we review
      the genetic diversity of connexins, structural proteins which form the gap
      junction, with emphasis on their tissue specific expression and present evidence
      that junctional communication is perturbed during the process of carcinogenesis.
      Finally we discuss the clinical implications of these findings in the light of
      recent experiments demonstrating that increased junctional communication,
      achieved by pharmacological or by molecular means, results in suppression of
      tumorigenicity or in enhanced growth control.

PMID- 7727723
TI  - Anti-oncogene and tumor suppressor gene therapy--examples from a lung cancer
      animal model.
AB  - Rapid advances in cancer gene therapy are driven by an explosive development of
      gene transfer technology and a strong demand for effective alternatives to
      unsatisfactory conventional cancer therapies. Discovery of the genetic basis of
      cancer has indicated that cancer is a disease of genes. Among a variety of
      approaches to gene therapy of cancer, anti-oncogene and tumor suppressor gene
      therapy of cancer are the two strategies that aim at correcting genetic disorders
      of cancer. The potential effectiveness of these approaches is promised by their
      precise targeting at the mechanisms of the disease. Successful examples of human
      lung cancer animal models by applying anti-K-ras retrovirus and recombinant p53
      adenovirus are reviewed. Future development of these approaches towards clinical
      application is also discussed.

PMID- 7727724
TI  - The ENCEL system: a somatic cell protein delivery system.
AB  - A wide variety of somatic cells are being explored for the introduction of
      foreign genes with a view toward gene therapy. A prime requirement for successful
      gene therapy is the sustained expression, effective dosing, and systemic delivery
      of the therapeutic gene product. Microvascular endothelial cells offer several
      advantages over other cell types as a somatic cell gene delivery vehicle in that
      they provide direct secretion of protein into the blood stream and they are
      amendable to highly stable retroviral-based protein expression. Importantly, they
      also offer a large surface volume to size ratio in that they can be induced with
      angiogenic factors to form organized capillary-like structures in vitro when
      grown in a three dimensional culture system using collagen gels. These
      genetically-modified capillary endothelial cells (the ENCEL system) maintained in
      collagen gels can be stably transplanted and removed. The unique biological
      properties of microvascular capillary endothelial cells allows the ENCEL system
      to provide large numbers of cells in a small volume which offers the highly
      desired opportunity for providing a sustained and effective dose of a therapeutic
      protein. Alexion is currently applying its Unigraft immunotherapeutic and
      engineering technologies to commercialize a non-human ENCEL system acceptable for
      implantation into any patient.

PMID- 7727725
TI  - Antisense tumor therapy (a dream under construction).
AB  - Cancer, as a genetic disease, is a logical target for gene-oriented therapy-
      either by replacing the missing/nonfunctioning gene or by depressing the activity
      of an unwanted gene. The latter is really the inhibition of gene expression using
      oligonucleotide-based or "antisense" treatment. There are several strategies to
      achieve this: anti-gene or anti-code with triplex formation; ribozyme with
      endogenous catalytic RNase activity; antisense with oligonucleotides through
      steric inhibition or RNaseH activation; and sense strategy to inhibit or trap
      proteins by nucleic acids. There are two essential partners of the approach:
      targeted sequence in the unwanted gene/molecule and the complementary antisense
      oligo (-ribo- or -deoxyribonucleotide). The antisense sequences require chemical
      modifications (mostly on the phosphodiester backbone, less in the sugar or in the
      bases) to avoid nucleases, to form complexes for better delivery (in the organism
      and also in the cell). The activity of the unwanted target should be non-randomly
      associated with cancer (e.g. abl/ber). Both aspects of antisense treatment
      require further improvements to get longer lasting and real sequence-specific
      antitumor effect which could be competitive with the available therapeutic
      modalities.

PMID- 7727726
TI  - Antisense therapy of cancer.
AB  - Binding sites for the NF-kappa B transcription factor complex, composed of two
      subunits, p50 (NFKB1) and p65 (rel A), are present in many cell adhesion
      molecules, cytokines, and growth-factor receptors. Antisense techniques were used
      to establish the role of NF-kappa B in cell growth. Surprisingly, antisense
      phosphorothioate oligomers to the rel A subunit of NF-kappa B caused a pronounced
      block of cellular adhesion. Since adhesion plays an important role in diseases
      including cancer and inflammation, this chance observation was extended to
      various in vitro and in vivo models. Our results establish the in vivo efficacy
      of phosphorothioate oligomers.

PMID- 7727727
TI  - Differentiation of HL-60 cells by dimethylsulfoxide activates a Na(+)-dependent
      nucleoside transport system.
AB  - Uridine transport in undifferentiated HL-60 cells occurs primarily by facilitated
      diffusion, but a limited Na(+)-dependent process can be demonstrated (Km = 44 +/-
      4.4 microM, Vmax = 0.13 +/- 0.01 microM/s). This latter transport system was
      inhibited by adenosine and inosine (Ki = 110 and 260 microM, respectively),
      whereas guanosine and thymidine were less effective (Ki = 1600 and 1200 microM,
      respectively). Dimethylsulfoxide (DMSO) caused a concentration-dependent decrease
      in facilitated uridine transport. This change was attributable to a decrease in
      the number of transporter molecules as determined by the binding of
      [3H]nitrobenzylthioinosine to cell membranes. Moreover, the Na(+)-dependent
      transport of uridine was enhanced by DMSO at a concentration of the polar solvent
      as low as 0.4%. When HL-60 cells were exposed to 1.0% DMSO, a marked increase in
      Na(+)-dependent uridine transport occurred within 72 hr, a time preceding maximum
      granulocytic differentiation. This change was attributable to an increase in
      transport affinity (Km = 1.54 +/- 0.65 microM), with no change in Vmax (Vmax =
      0.13 +/- 0.02 microM/s). The consequence of these changes was the generation of a
      3- to 4-fold increase in the intracellular concentration of uridine relative to
      the medium at a physiological concentration of 5 microM uridine. Similar
      increases in transport affinity were observed for adenosine, inosine, guanosine
      and thymidine in DMSO-differentiated HL-60 cells (Km values of 2 to 5 microM).
      These results complement our previous studies with phorbol 12-myristate 13
      acetate, in which differentiation to a monocytic phenotype was also associated
      with enhanced Na(+)-dependent nucleoside transport.

PMID- 7727728
TI  - Neuroendocrine modulation of tumor metastases. I. Effect of adrenalectomy on B16
      melanoma metastases.
AB  - There is increasing evidence to suggest a link between the neuroendocrine system
      and the immune system. Since it is well known that the immune response influences
      the establishment, progression or elimination of malignancy, we have examined the
      effects of adrenalectomy on B16 melanoma pulmonary tumor metastases and immune
      function in C57BL/6 mice to investigate the role of adrenal corticosteroids.
      Adrenalectomized mice were injected with 10(5) B16 melanoma cells on day 0. On
      day 9 the mice were sacrificed and the number of lung colonies counted.
      Adrenalectomized animals had a greater than 3 to 4-fold increase in the number of
      metastases as compared with sham operated animals. Steroid replacement therapy
      using dexamethasone delivered at 1 microgram/hr did not lead to any reduction in
      tumor metastases in adrenalectomized animals. These studies indicate that normal
      levels of adrenal steroids may influence the ability of tumor cells to colonize
      target organs and/or the ability of the immune system to mount an effective
      response.

PMID- 7727729
TI  - Cancer cytogenetics and molecular genetics: detection and therapeutic strategy.
AB  - It has become increasingly evident that cancers are "genetic diseases" resulting
      from an accumulation of inherited and environmentally-induced changes or
      mutations in the genome, i.e., the modification, activation, or inactivation of
      various genes, including oncogenes, tumor-suppressor genes, and genes related to
      cell death. Cancer genetics has, therefore, become a burgeoning area of both
      cytogenetic/molecular genetic research and practical clinical application in
      human cancer. This article summarizes the specific types of chromosomal and
      associated molecular genetic alterations in leukemia and cancer. The emphasis is
      on the application of cytogenetics and molecular cytogenetics as diagnostic,
      prognostic and therapeutic indices, as approaches to the evaluation of minimal
      residual disease and as guides for differentiation therapy and the molecular
      localization of oncogenes/tumor suppressor genes related to gene therapy in
      leukemias and cancers. This review is intended to update physicians of various
      disciplines on the rapid advances that have been made in the understanding of the
      chromosomal and molecular basis of cancer and in approaches for improving the
      management of cancer patients through knowledge of genetics.

PMID- 7727730
TI  - Synergistic cytotoxic and antitumor effects of irradiation and taxol on human
      HeLa cervix carcinoma and mouse B16 melanoma cells.
AB  - Several articles have appeared in the scientific literature which report that
      taxol has the ability to block and/or prolong cells in the G2/Mp phase of the
      cell cycle by inducing extremely stable microtubules. The G2/M phase is known to
      be the most radiosensitive phase of the cell cycle. It is the purpose of this
      study to evaluate the effect of combination taxol and ionizing radiation on tumor
      cell lines which have not been previously reported in the literature. Decrease in
      viability and inhibition of proliferation of HeLa and B16 cells induced by
      irradiation were dose-dependent and significantly enhanced by pretreatment the
      cells with taxol. Similar antitumor effects of irradiation and taxol were
      demonstrated by flow cytometric analysis of chromatic fragment formation induced
      in these cells. The exact mechanism by which taxol enhanced the tumoricidal
      effect of irradiation is not known. Cell cycle analysis showed that taxol was
      effective in blocking HeLa and B16 cells at the G2/M stage, at which the tumor
      cells are believed to be most sensitive to irradiation. This study is in
      agreement with others who have found that taxol is a powerful radiation
      sensitizer. Clinical research protocols have been developed and are under way to
      determine if taxol produces similar synergistic effects in patients undergoing
      radiation therapy.

PMID- 7727731
TI  - Feline breast carcinoma as a pathologic and therapeutic model for human breast
      cancer.
AB  - The United States pet population has been a vastly underutilized resource for
      cancer therapy studies. Naturally occurring tumors in pet animals develop twice
      as frequently as in man, have histopathologic features and a biologic behavior
      similar to tumors in man, and progress at a more rapid rate than in man. Cancer
      of the breast is the most common major cancer in women and the third most
      commonly reported cancer in cats. Breast cancer is probably the most feared
      cancer in women because of its frequency and its psychological impact. Breast
      cancer in the cat is highly malignant, rapidly metastasizing, and often a fatal
      disease. This report will discuss the comparative nature of breast cancer and the
      advantage of using the tumor-bearing cat as a pathologic and therapeutic model
      for the study of human breast cancer.

PMID- 7727732
TI  - Modes of resistance to antitumor agents.
AB  - Drug resistance has complicated chemotherapy of neoplastic disease since the
      early beginnings of the field. Successful use of drug therapy requires that tumor
      cells be more drug-responsive than the tissue of origin. This can occur with
      rapidly-dividing tumors which will be highly-responsive to drugs toxic in the S
      phase of the cell cycle. Another drug sensitive population will consist of
      neoplastic cells unable to repair drug-induced damage which can be repaired by
      normal host cells. Even if one of these conditions is initially found, mutational
      events leading to drug resistance often occur. The most thoroughly explored mode
      of drug resistance involves MDR (multidrug resistance), an outward transport
      system which limits penetration of a variety of cytotoxic agents into the
      cytoplasm and nucleus. MDR is expressed by many normal cell types, and attempts
      at MDR circumvention appear to lead to new modes of host toxicity. It appears
      that new directions in cancer therapy will be needed to yield responses in the
      common slow-growing tumors which tend to be inherently drug-resistant.

PMID- 7727733
TI  - Regulation of the multidrug resistance (MDR1) gene expression.
AB  - The emergence of drug resistance poses a major obstacle to the success of
      chemotherapy for a large number of human cancers. Development of the multidrug
      resistance phenotype in human malignancies is an especially pressing problem
      because the tumors become cross-resistant to multiple chemotherapeutic agents
      that are both chemically and physically unrelated. The increased resistance to
      multiple cytotoxic natural product chemotherapeutic drugs is due to
      overexpression of the mdr gene, which encodes a plasma membrane ATP-dependent
      efflux pump. Expression of P-glycoprotein is tissue specific and found in a
      number of normal tissues, including colon, small intestine, kidney, liver and
      adrenal gland, as well as in the capillaries of brain and testis. The precise
      physiological functions in these tissue localizations is unclear at present.
      Intense efforts in many laboratories currently are invested on elucidating the
      functions of P-glycoprotein and investigating mechanisms that regulate the mdr
      gene expression.

PMID- 7727734
TI  - Chromosome alterations in cancer development and apoptosis.
AB  - Normal somatic cells are programmed to die (or undergo apoptosis) whereas cancer
      cells program themselves to survive. Some of the cytogenetic alterations that
      might be involved in apoptosis and continuous cell proliferation of normal and
      cancer cells such as shortening of telomeres, formation of dicentric chromosomes,
      transfer of telomeric DNA to the homologous chromosomes, malfunction
      (inactivation) of the centromeres, endoreduplication of chromosomes and other
      structural and numerical chromosome abnormalities are discussed here.

PMID- 7727735
TI  - Therapeutic hyperthermia: contribution from clinical studies in dogs with
      spontaneous neoplasia.
AB  - Dogs with spontaneously arising tumors have contributed greatly to the field of
      therapeutic hyperthermia. Pharmacologic, physiologic and immunologic
      characterization of the response to hyperthermia combined with radiation and
      chemotherapy in dogs has helped in development of new heating methods, warned of
      significant toxicity prior to human testing, and defined the effect of heat on
      drug distribution and relative potency. Clinical trials have been conducted in
      dogs with spontaneously arising cancer to refine treatment protocols prior to
      human clinical testing and have demonstrated the tumor control advantage of
      combined radiation/hyperthermia compared to radiation only in numerous
      prospective, phase III trials. These studies can be conducted less expensively
      and more rapidly than comparable studies in humans. This paradigm demonstrates
      the value of an intermediate, clinically relevant model in the study of novel
      treatment strategies and should continue to be used to investigate important
      issues for the benefit of both humans and animals with cancer.

PMID- 7727736
TI  - Production of polypeptide regulatory factors by human melanoma cells.
AB  - Peptide regulatory factors, i.e. cytokines, are released spontaneously or upon
      induction by melanoma cells in culture. Among these cytokines there are factors
      such as Il-1, IL-6, IL-8, IL-10 as well as TGF-beta 1 which are basically acting
      as immunoregulatory molecules. However, their contribution to an augmentation
      and/or suppression of local or systemic immune response against melanoma cells in
      situ has not yet been elucidated. On the other hand, some of these molecules,
      e.g. IL-6 and TGF-beta 1, are growth inhibitors, especially in the early phases
      of melanoma development. During tumor progression, resistance to the inhibitory
      effect of these cytokines seems to take place. Whether this resistance is due to
      an excessive production of these cytokines or a downregulation or blockade of
      receptors is still controversial. The aberrant expression of bFGF in melanoma
      cells explains how melanoma cells in vitro and probably also in vivo acquire
      growth autonomy and the capacity of metastasis formation. The expression of bFGF
      by human melanoma cells and its activity as autocrine growth regulator imply that
      agents which interfere with heparin-binding growth factors such as Suramin or
      pentosan sulfate may be of clinical usefulness. Additionally, these latter agents
      have been shown to be potent anti-angiogenic factors. Their clinical efficacy,
      however, has to be established in phase I and II studies.

PMID- 7727737
TI  - Is taxol a surrogate for a universal regulator of mitosis?
AB  - Taxol is well recognized as an antitumor agent and a biochemical tool for studies
      of microtubules. A proposal is made that taxol is a surrogate for a key
      endogenous regulator of microtubules, which has the particular function of
      stabilizing the mitotic spindle. This proposal is based on evidence from the
      breadth of taxol activity across organisms, data supporting a highly conserved
      binding site for taxol, low-dose effects of taxol targeting the mitotic spindle,
      the restriction of the binding site to a highly conserved segment of B-tubulin,
      data on the biosynthesis and distribution of taxol, and the recent discovery of
      an anti-idiotype antibody with taxol-like activity.

PMID- 7727738
TI  - Ethylene dibromide: evidence of systemic and immunologic toxicity without
      impairment of in vivo host defenses.
AB  - Ethylene dibromide was administered intragastrically on 14 consecutive days to
      B6C3F1 female mice. Host resistance was not altered after challenge with B16F10
      tumor cells, Listeria monocytogenes, influenza, or Herpes simplex viruses. In
      contrast, decreases were seen in relative thymus and spleen weights, red blood
      cells, hemoglobin, hematocrit, and in alveolar macrophage, natural killer cell, T
      cell, and mixed lymphocyte culture responses. Increases occurred in relative
      kidney and liver weights, cholesterol, peripheral neutrophils, resident
      peritoneal exudate cells (with increased phagocytosis) and plaque-forming cells.
      There was little difference between the dose that caused immune modulation and
      that which produced significant toxicity.

PMID- 7727739
TI  - Diagnosis and surgical treatment of reptilian neoplasms with a compilation of
      cases 1966-1993.
AB  - Neoplasia is not rare in lower vertebrates, and the tumour types closely resemble
      those observed in mammals. Because of some unique anatomical and cytological
      features found only in reptiles, a few unusual types of neoplasia that are not
      seen in mammals occur in reptiles. Diagnosis and surgical treatment of benign and
      malignant spontaneous tumours and leukaemias generally parallel the methods
      employed in mammals; these include radiographic and other forms of non-invasive
      imaging, fine-needle and excisional biopsy, exfoliative cytology, and
      haematology. Treatment consisting of conventional sharp excisional,
      radiofrequency, and cryosurgical techniques are most often employed.
      Histopathologically confirmed tumours diagnosed in snakes, lizards, and
      chelonians during the 27-year period between 1 January 1966 and 31 December, 1993
      were enumerated and, where appropriate, the epidemiological, pathophysiological,
      and biological features of these cases were investigated.

PMID- 7727740
TI  - Interspecies comparative pathology of colorectal neoplasms: relevance for
      treatment.
AB  - Comparative pathology may serve as a practical tool for therapy by comparison of
      normal and abnormal structures of the digestive tract in animals and men. A
      better understanding of colon cancer as the most common solid neoplasm after lung
      cancer in the industrialized world is sought. In the so-called developed nations
      and in animals colon cancer is less frequent. The pathogenesis of colon cancer
      involves environmental and genetic factors. Several types of colorectal cancer
      can be discerned and the species distribution ranges from invertebrates to man.
      Colorectal neoplastic progression is species-specific. An intraspecies-specific
      comparison of large bowel cancer is also valuable. Alteration of signal
      transduction pathways and somatic mutations of oncogenes are described, as well
      as the occurrence, research and current treatment. Metastasis of neoplasms of the
      colon and of the rectum can be studied by intraspecies-specific comparison.
      Sections of this review deal with vitamin D and cancer and close with present
      therapies for colorectal cancer.

PMID- 7727741
TI  - Development of lymphopoiesis as a function of the thymic microenvironment. Use of
      CD8+ cytotoxic T lymphocytes for cellular immunotherapy of human cancer.
AB  - The mammalian thymic histogenesis can be immunomorphological divided into three
      consecutive states: 1) Epithelial: 2) Lymphopoietic or lympho-epithelial and 3)
      Differentiated cellular microenvironment with formation of Hassall's bodies. The
      embryonic, epithelial pharynx serves as the origin of the mammalian thymus. The
      epithelial cell layer of endodermic origin expands into pharyngeal pouches and
      the thymic anlagen are formed from the dorsolateral portions of the third
      pharyngeal pouch. In absence of humoral and cell to cell interactions with the
      ectomesenchyme, the primary epithelial anlagen are unable to proliferate.
      Experimental or spontaneous neural crest ablation early in ontogenesis also
      results in non-physiologic thymic organogenesis. Earlier thymic studies detected
      a subcapsular A2B5+ and Thy-11+, TE4+, Vimentin+, Cytokeratin+ endocrine reticulo
      epithelial cell or nurse cell subpopulation within the cortical reticulo
      epithelial cell network. Secretion of multiple in situ active, autocrine growth
      factors and a humoral chemotactic factor by the cells of ectomesenchymal origin
      allows the commencement of immigration of hemopoietic stem cells. The thymic
      lymphopoiesis is initiated by the immigration of pluripotent (with cellular
      immunophenotype TdT+, Ki67+, CD3-, CD7+, CD34+, CD38+, CD44+, CD45+ or T200+),
      but already to T lymphocyte cell lineage committed hemopoietic stem cells during
      the 6-7th week of ontogenesis. CD2, a 50-55 kD glycoprotein is the first
      intrathymic, early differentiation antigen expressed during the 8-9th ontogenetic
      weeks. This antigen also serves as a cell surface component of the alternative or
      antigen independent pathway of thymocyte activation. The 10th week is defined as
      the first expression of CD4 and CD8 antigens which determine the basic,
      characteristic dichotomy of the T lymphocytes. The induction of the initial
      proliferative wave of immature cortical thymocytes is carried out by the LFA-3
      (CD58) adherence molecules, the receptors of CD2 antigens located on reticulo
      epithelial cells. As a result of the extremely high proliferation rate the thymic
      mass markedly expands in all dimensions and numerous microlobules are formed.
      Between the 13th to 16th week the typical thymic cell environment is formed and
      the first Hassall's bodies are developed. The outer layer of the bodies contain
      hypertrophized TE8+, TE16+ and TE19+ reticulo-epithelial cells, with an active
      secreting cytoplasmic structure. Cytotoxic cells express special receptors by
      which they are capable to distinguish altered or foreign cells from autologous
      cells of the host. Solid human tumors are characterized with a marked poly- and
      mononuclear cell infiltrate containing phagocytes, various subtypes and clones of
      lymphocytes and granulocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7727742
TI  - Autopsy as clinical quality control: a study of 15,143 autopsy cases.
AB  - The results of autopsy records at the Institute of Pathology of Munster
      University documented between 1961-70, 1978-87 and 1988-92 were compared with the
      documented clinical diagnoses of these cases. In the decade 1961-70, 23% of
      clinical diagnoses were found incorrect (with therapeutic relevance). In the
      decade 1978-87, the error rate was 18% and in 1988-92, 12%. The difference
      between the three groups was statistically significant (p < 0.01). Specific data
      were assembled for the main malignant tumor types. With respect to infectious
      diseases, the agreement between clinical and autopsy diagnosis is even poorer.
      Lues (syphilis) is now rarely recognized in clinical diagnosis, even if it is
      fatal. Merely 50% of all patients with active tuberculosis as primary disease and
      cause of death, had been diagnosed clinically. Endocarditis in all its forms was
      underdiagnosed clinically in 75% of the cases. In view of the widely ranging
      discussion about the value of autopsy today, and in view of the fact that in
      epidemiological studies the correctness of in vivo diagnosis is tacitly presumed,
      it has to be stated that autopsy is the best quality control for progress in
      clinical medicine.

PMID- 7727743
TI  - A pollen-specific DEAD-box protein related to translation initiation factor eIF
      4A from tobacco.
AB  - A pollen-specific sequence, NeIF-4A8, has been isolated from a cDNA library from
      mature pollen of Nicotiana tabacum cv. Samsun. NeIF-4A8 is a full-length cDNA
      whose deduced amino acid sequence exhibits high homology to the eucaryotic
      translation initiation factor eIF-4A from mouse, Drosophila and tobacco. eIF-4A
      is an RNA helicase which belongs to the supergene family of DEAD-box proteins.
      Northern blot analysis with a gene-specific probe showed strict anther-specific
      expression of NeIF-4A8 starting at microspore mitosis. With antibodies raised
      against tobacco eIF-4A the presence of abundant eIF-4A-related proteins in
      developing anthers and pollen grains was demonstrated. The genomic analysis shows
      that the coding region is split by three introns whereas a large, fourth intron
      is situated in the 5'-untranslated region. A promoter construct with 2137 bp of
      upstream sequence fused to the GUS reporter gene was used to confirm that the
      expression is confined to the haploid cells within the anther. NeIF-4A8 is a
      prime candidate formediating translational control in the developing male
      gametophyte.

PMID- 7727744
TI  - Tissue- and cell-specific expression of a cinnamyl alcohol dehydrogenase promoter
      in transgenic poplar plants.
AB  - Cinnamyl alcohol dehydrogenase (CAD) which catalyses the synthesis of the
      cinnamyl alcohols, the immediate precursors of lignins, from the corresponding
      cinnamaldehydes is considered to be a highly specific marker for lignification.
      We have isolated and characterized a CAD genomic clone from eucalyptus, a woody
      species of economic importance. The full-length promoter (EuCAD, 2.5 kb) and a
      series of 5' deletions were fused to the beta-glucuronidase (GUS) reporter gene.
      These constructs were tested in a homologous transient expression system of
      eucalyptus protoplasts which enabled the identification of several regions
      involved in transcriptional control. In order to study the spatial and
      developmental regulation of the CAD gene, the chimeric gene fusion (EuCAD-GUS)
      was then transferred via Agrobacterium tumefaciens-mediated transformation into
      poplar, an easily transformable woody angiosperm. Quantitative fluorometric
      assays conducted on eight independent in vitro transformants showed that GUS
      activity was highest in roots followed thereafter by stems and leaves.
      Histochemical staining for GUS activity on both in vitro primary transformants
      and more mature greenhouse-grown plants indicated a specific expression in the
      vascular tissues of stems, roots, petioles and leaves. At the onset of xylem
      differentiation, GUS activity was detected in parenchyma cells differentiating
      between the xylem-conducting elements. After secondary growth has occurred, GUS
      activity was localized in xylem ray cells and parenchyma cells surrounding the
      lignified phloem and sclerenchyma fibers. This first characterization of a woody
      angiosperm CAD promoter provides functional evidence for the role of CAD in
      lignification and suggests that parenchyma cells expressing CAD may provide
      lignin precursors to the adjacent lignified elements (vessels and fibres).

PMID- 7727745
TI  - Characterization of the signal recognition particle (SRP) RNA population of
      tomato (Lycopersicon esculentum).
AB  - Molecular cloning of 30 cDNAs and subsequent characterization of the
      corresponding SRP RNA from four cultivars of tomato (Lycopersicon esculentum)
      revealed altogether 14 sequence variants, which could be ordered into six groups.
      The expression of five representatives from these groups was examined by reverse
      transcriptase-polymerase chain reaction (RT-PCR) in different cultivars and
      different tissues. Although one cultivar-specific SRP RNA variant could be
      detected in the leaf SRP RNA population, identical SRP RNA populations seem to be
      present in the four different cultivars as well as in different tissues, such as
      leaves, flowers, fruits, stems and roots. Sequence comparison revealed that
      several variants might have evolved by recombination of two different SRP RNA
      sequences. On the basis of five SRP RNA variants, the current secondary structure
      model was refined and a new conserved structural element was detected.
      Comparative sequence analysis of domain II from all known SRP RNA homologues
      reveals a remarkable conservation of this element. As demonstrated previously,
      the corresponding area overlaps with a region that interact with the SRPp68/p72
      heterodimer and/or with ribosomes. Based on structural and functional
      considerations, we propose that the domain IV structure together with the highly
      conserved area of domain II constitutes the essential core of the SRP RNA.

PMID- 7727746
TI  - Molecular cloning and heterologous expression of acridone synthase from elicited
      Ruta graveolens L. cell suspension cultures.
AB  - Cell suspension cultures of Ruta graveolens L. produce a variety of acridone
      alkaloids, and the accumulation can be stimulated by the addition of fungal
      elicitors. Acridone synthase, the enzyme catalyzing the synthesis of 1,3
      dihydroxy-N-methylacridone from N-methylanthraniloyl-CoA and malonyl-CoA, had
      been isolated from these cells, and the partial enzyme polypeptide sequence,
      elucidated from six tryptic fragments, revealed homology to heterologous chalcone
      synthases. Poly(A)+ RNA was isolated from Ruta cells that had been treated for 6
      h with a crude cell wall elicitor from Phytophthora megasperma f. sp. glycinea,
      and a cDNA library was constructed in lambda 2AP. Clones harboring acridone
      synthase cDNA were isolated from the library by screening with a synthetic
      oligonucleotide probe complementary to a short stretch of sequence of the enzyme
      peptide with negligible homology to chalcone synthases. The identity of the
      clones was substantiated by DNA sequencing and by recognition of five additional
      peptides, determined previously from tryptic acridone synthase digests, in the
      translated sequence. An insert of roughly 1.4 kb encoded the complete acridone
      synthase, and alignments at both DNA and protein levels corroborated the high
      degree of homology to chalcone synthases. Expression of the enzyme in vector pET
      11c in the Escherichia coli pLysS host strain proved the identity of the cloned
      cDNA. The heterologous enzyme in the crude E. coli extract exhibit high acridone
      but no chalcone synthase activity. The results were fully supported by northern
      blot hybridizations which revealed that the specific transcript abundance did not
      increase but rather decreased upon white light irradiation of cultured Ruta
      graveolens L. cells, a condition that commonly induces the abundance of chalcone
      synthase transcripts.

PMID- 7727747
TI  - Calmodulin gene family in potato: developmental and touch-induced expression of
      the mRNA encoding a novel isoform.
AB  - Eight genomic clones of potato calmodulin (PCM1 to 8) were isolated and
      characterized. Sequence comparisons of different genes revealed that the deduced
      amino acid sequence of PCM1 had several unique substitutions, especially in the
      fourth Ca(2+)-binding area. The expression patterns of different genes were
      studied by northern analysis using the 3'-untranslated regions as probes. The
      expression of PCM1, 5, and 8 was highest in the stolon tip and it decreased
      during tuber development. The expression of PCM6 did not vary much in the tissues
      tested, except in the leaves, where the expression was lower; whereas, the
      expression of PCM4 was very low in all the tissues. The expression of PCM2 and
      PCM3 was not detected in any of the tissues tested. Among these genes, only PCM1
      showed increased expression following touch stimulation. To study the regulation
      of PCM1, transgenic potato plants carrying the PCM1 promoter fused to the beta
      glucuronidase (GUS) reporter gene were produced. GUS expression was found to be
      developmentally regulated and touch-responsive, indicating a positive correlation
      between the expression of PCM1 and GUS mRNAs. These results suggest that the 5'
      flanking region of PCM1 controls developmental and touch-induced expression. X
      Gluc staining patterns revealed that GUS localization is high in meristematic
      tissues such as the stem apex, stolon tip, and vascular regions.

PMID- 7727748
TI  - An intrinsically bent region upstream of the transcription start site of the rRNA
      genes of Arabidopsis thaliana interacts with an HMG-related protein.
AB  - Intrinsically bent DNA structures are thought to play crucial roles as
      functionally important modules in promoter/enhancer elements. Here we show the
      existence of a DNA bending centre within the intergenic region of the tandemly
      arranged rRNA genes of Arabidopsis thaliana. By use of a circular permutation
      assay, this bending centre was localized to position -284 to -256 upstream of the
      transcription start site. A 143 bp fragment containing the bent region was shown
      to interact with several nuclear proteins. Evidence is presented that one of
      these proteins is related to the high-mobility-group (HMG) proteins, a group
      thought to be involved in transcription and replication processes.

PMID- 7727749
TI  - The Pisum sativum TubA1 gene, a member of a small family of alpha-tubulin
      sequences.
AB  - alpha- and beta-tubulin proteins are subunits of microtubules, which as primary
      elements of the plant cytoskeleton play major roles in plant cell division and
      cell morphogenesis. Several higher-plant alpha- and beta-tubulin gene families
      have been reported to have at least six to nine members each. Using genomic
      Southern hybridizations and polymerase chain reaction (PCR) experiments, we have
      found that the Pisum sativum (garden pea) genome has only four copies of alpha
      tubulin sequences and a similar number of beta-tubulin sequences. We have
      characterized the pea alpha-tubulin gene TubA1. Its nucleotide sequence predicts
      a 452 amino acid product which is 89-98% identical to those predicted for other
      plant alpha-tubulins. By S1 nuclease analysis we have located the transcript
      start site at 102 bases upstream of the ATG. We have also shown that the TubA1
      gene is expressed by northern hybridization with a gene-specific probe.

PMID- 7727750
TI  - Promoter analysis of seed storage protein genes from Canavalia gladiata D.C.
AB  - A number of A/T-rich sequences and a CATGCAT/A sequence are contained in the 5'
      upstream regions of the genes encoding concanavalin A (Con A) and canavalin, two
      major seed storage proteins of Canavalia gladiata D.C. To study the role of these
      sequences in the seed-specific gene expression, we constructed 5'-deletion
      mutants and examined the transient expression of beta-glucuronidase reporter gene
      by particle bombardment and the stable expression by Agrobacterium-mediated
      transformation of tobacco plants. Positive regulatory elements were located in
      the -894/-602 and -602/-74 regions of the Con A gene, and in the -428/-376, -281/
      155 and -155/-50 regions of the canavalin gene. In addition, the results
      suggested that the A/T-rich sequences in the 5'-upstream region of the Con A gene
      play a role in transcriptional activation, but that those of the canavalin gene
      have little effect on the gene expression. The CATGCAT/A sequence was not
      sufficient by itself for high levels of expression of both the Con A and
      canavalin genes. The canavalin polypeptide amounted to about 1% of the total
      extractable protein in the transgenic tobacco seeds, but the Con A polypeptide
      was not detected in the extractable protein.

PMID- 7727751
TI  - GASA, a gibberellin-regulated gene family from Arabidopsis thaliana related to
      the tomato GAST1 gene.
AB  - A multiple gene family of at least four members, related to a GA-stimulated
      transcript (GAST1) from tomato, was characterized in Arabidopsis thaliana by
      analysing four related cDNAs, named GASA1 to GASA4. The corresponding peptides
      display comparable structural features: (1) a putative signal peptide of 18 to 23
      residues; (2) a highly divergent hydrophilic region of about 22 amino acids; (3)
      a conservative 60 amino acid C-terminal domain containing 12 cysteines. This
      organization has also bean shown in two related peptides from tomato, GAST1 found
      in shoots and RSI-1 found in early lateral roots. Southern blot hybridization
      patterns showed single-copy genes for all four members of the GASA family.
      Accumulation of the various transcripts, monitored by northern blot
      hybridization, indicated that the various genes are expressed differentially in
      plant organs: Specific mRNAs were mostly detected in flower buds and immature
      siliques in the case of GASA1, in siliques and dry seeds in the case of GASA2 and
      3, and in growing roots and flower buds in the case of GASA4. At least two of the
      GASA genes are activated in GA-deficient mutant ga5, as early as 4 to 8 h after
      spraying with 50 microM GA3. The complex patterns of expression and regulation of
      the various genes suggest that the related peptides are involved in a
      developmental regulation process in Arabidopsis.

PMID- 7727752
TI  - Existence of two ferredoxin-glutamate synthases in the cyanobacterium
      Synechocystis sp. PCC 6803. Isolation and insertional inactivation of gltB and
      gltS genes.
AB  - The first two genes of ferredoxin-dependent glutamate synthase (Fd-GOGAT) from a
      prokaryotic organism, the cyanobacterium Synechocystis sp. PCC 6803, were cloned
      in Escherichia coli. Partial sequencing of the cloned genomic DNA, of the 6.3 kb
      Hind III and 9.3 kb Cla I fragments, confirmed the existence of two different
      genes coding for glutamate synthases, named gltB and gltS. The gltB gene was
      completely sequenced and encodes for a polypeptide of 1550 amino acid residues
      (M(r) 168,964). Comparative analysis of the gltB deduced amino acid sequence
      against other glutamate synthases shows a higher identity with the alfalfa NADH
      GOGAT (55.2%) than with the corresponding Fd-GOGAT from the higher plants maize
      and spinach (about 43%), the red alga Antithamnion sp. (42%) or with the NADPH
      GOGAT of bacterial source, such as Escherichia coli (41%) and Azospirillum
      brasilense (45%). The detailed analysis of Synechocystis gltB deduced amino acid
      sequence shows strongly conserved regions that have been assigned to the 3Fe-4S
      cluster (CX5CHX3C), the FMN-binding domain and the glutamine-amide transferase
      domain. Insertional inactivation of gltB and gltS genes revealed that both genes
      code for ferredoxin-dependent glutamate synthases which were nonessential for
      Synechocystis growth, as shown by the ferredoxin-dependent glutamate synthase
      activity and western-blot analysis of the mutant strains.

PMID- 7727753
TI  - Studies on the import and processing of the alternative oxidase precursor by
      isolated soybean mitochondria.
AB  - Import of the synthetic precursor of the alternative oxidase from soybean was
      shown to be dependent on a membrane potential and ATP. The membrane potential in
      soybean mitochondria may be formed either by respiration through the cytochrome
      pathway, or through the alternative oxidase pathway with NAD(+)-linked
      substrates. Import of the alternative oxidase precursor in the presence of
      succinate as respiratory substrate was inhibited by KCN. Import in the presence
      of malate was insensitive to KCN and SHAM added separately, but was inhibited by
      KCN and SHAM added together (inhibitors of the cytochrome and alternative
      oxidases respectively). Import of the alternative oxidase was accompanied by
      processing of the precursor to a single 32 kDa product in both cotyledon and root
      mitochondria. This product had a different mobility than the two alternative
      oxidase bands detected by immunological means (34 and 36 kDa), suggesting that
      the enzyme had been modified in situ. When the cDNA clone of the alternative
      oxidase was modified by a single mutation (-2 Arg changed to -2 Gly), the
      processing of the precursor was inhibited.

PMID- 7727754
TI  - A protein is involved in accessibility of the inhibitor acetazolamide to the
      carbonic anhydrase(s) in the cyanobacterium Synechocystis PCC 6803.
AB  - A gene, zam (for resistance to acetazolamide), controlling resistance to the
      carbonic anhydrase inhibitor acetazolamide, is described. It has been cloned from
      a spontaneous mutant, AZAr-5b, isolated from the cyanobacterium Synechocystis PCC
      6803, for its resistance to this drug (Bedu et al., Plant Physiol 93: 1312-1315,
      1990). This mutant, besides its resistance to acetazolamide, displayed an absence
      of catalysed oxygen exchange activity on whole cells, suggestive of a deficiency
      in carbonic anhydrase activity. The gene was isolated by screening a genomic
      library of AZAr-5b, and selecting for the capacity to transfer the AZAr phenotype
      to wild-type cells. A system leading to forced homologous recombination in the
      host chromosome, using a platform vector, was devised in order to bypass direct
      selection difficulties. The putative encoded protein, 782 amino acids long,
      showed some homology with four eukaryotic and prokaryotic proteins involved in
      different cellular processes, one of them suppressing a phosphatase deficiency.
      The mutated allele of AZAr-5b showed an in-frame 12 nucleotide duplication, which
      should not interfere with translation, and might result from transposition of a
      mobile element. Integration into a wild-type genome of either the spontaneous
      mutated allele or one inactivated by insertional mutagenesis conferred the
      character of resistance, but not the deficiency in oxygen exchange, indicating
      that the two phenotypic aspects of AZAr-5b corresponded to two independent
      mutations. A working hypothesis explaining the phenotypes of the mutants is that
      the presence of the Zam protein would be necessary for the inhibitor to reach
      (one of) the two carbonic anhydrases present in this strain. This, however, would
      be a secondary action, the physiological role of the protein still being cryptic.

PMID- 7727756
TI  - Genetic correlation of the orf224/atp6 gene region with Polima CMS in Brassica
      somatic hybrids.
AB  - To identify regions of the mitochondrial genome from the polima or pol male
      sterile cytoplasm of Brassica napus that are genetically correlated with
      cytoplasmic male sterility (CMS) we analyzed mtDNAs of three male-sterile somatic
      hybrids formed by the fusion of broccoli (B. oleracea L. var. italica) and pol
      CMS B. napus protoplasts. Fragments characteristic of a 4.5 kb DNA segment that
      comprises the single organizational difference between sterile pol and fertile
      cam Brassica mitochondrial genomes were found in all three sterile somatic
      hybrids. One of these hybrids possessed a mitochondrial genome that was, apart
      from a limited region around this 4.5 kb CMS-associated segment, collinear with
      B. oleracea mtDNA. Previous studies have indicated that expression of transcripts
      spanning the atp6 gene and a chimeric gene, orf24, located on this 4.5 kb DNA
      segment, is associated with male sterility. The present results indicate that the
      orf224/atp6 gene region is genetically correlated with male sterility and provide
      significant additional support for the view that this gene region may be involved
      in specifying the CMS trait.

PMID- 7727755
TI  - Electron transport controls transcription of the glutamine synthetase gene (glnA)
      from the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The glnA gene, encoding type I glutamine synthetase (GS) in Synechocystis sp. PCC
      6803, showed a high sequence similarity with other cyanobacterial glnA genes. A
      dramatic decrease in the amount of glnA mRNA, a single transcript of about 1.6
      kb, was observed after transfer to darkness, or after incubation with the
      electron transport inhibitors DCMU or DBMIB. The levels of glnA transcript were
      fully recovered after 5 min of reillumination. The glnA mRNA was found to be
      equally stable both in the light and the dark (half-life about 2.5 min). Unlike
      the glnA messenger, the amount of GS protein was not reduced in the dark.
      Synthesis of the glnA transcript in the dark required the presence of glucose. In
      addition, glnA transcription in a Synechocystis psbE-psbF mutant lacking
      photosystem II required the presence of glucose even when grown in the light.
      These observations indicate that glnA transcription is under the control of the
      redox state of the cell. Finally, nitrogen starvation provoked a delay in the
      decrease of glnA transcript in darkness, suggesting a connection between nitrogen
      and redox controls of glnA transcript levels.

PMID- 7727757
TI  - Isolation of new promoter-mediated co-suppressed lines in Arabidopsis thaliana.
AB  - Four new independent lines that exhibit co-suppression of an introduced
      cab140::tms2 gene and the native cab140 gene have been isolated in Arabidopsis
      thaliana. These lines are of particular interest because the homology shared
      between the introduced and native genes is 1.3 kb of promoter DNA that only
      contains 14 bp of transcribed region. Most other reported examples of co
      suppression involve homologies between transcribed portions of genes. A similar
      line, lct, had been isolated previously from EMS-mutagenized seeds, and we
      concluded that this example of co-suppression was probably due to a mutation that
      mapped at or near the introduced cab140::tms2 gene [Brusslan JA, Karlin-Neumann
      GA, Huang L, Tobin EM: Plant Cell 5: 667-677 (1993)]. Our observations with these
      four new lines, however, suggest that an epigenetic event(s) rather than a
      mutation might be the cause of co-suppression in these and the lct line.

PMID- 7727758
TI  - The effect of intracellular pH on the regulation of the Rab 16A and the alpha
      amylase 1/6-4 promoter by abscisic acid and gibberellia.
AB  - Intracellular pH (pHi) of barley aleurone cells is known to be affected by
      hormones and plant growth conditions. The possible mechanisms by which these pHi
      shifts influence the actions of abscisic acid (ABA) or gibberellin (GA) is being
      investigated. Here we report an attempt to study the effect of pHi on hormone
      induced gene expression. We used weak acids and weak bases to artificially mimic
      the pHi changes brought about by ABA and GA and found that chloramphenicol
      acetyltransferase (CAT) expression controlled by the Rab promoter was affected
      while the alpha-amylase promoter seemed insensitive. CAT fused to the 35S
      promoter was used as a control which is not inducible by ABA or GA3. The
      expression of this construct was not significantly affected by artificial pHi
      changes.

PMID- 7727759
TI  - Cloning of a pea cDNA encoding a polypeptide of the light-harvesting complex
      associated with photosystem I using a monoclonal antibody.
AB  - A monoclonal antibody (MAb UB42) is described that binds to thylakoids in pea
      chloroplasts, as shown by EM-immunogold labelling. The antibody recognised
      proteins of ca. 23-29 kDa in western blots of a pea leaf homogenate. A cDNA
      library was prepared from pea epidermal cells in the vector lambda ZAP II, and
      immunoscreening of the library with UB42 led to the isolation of a clone, pUB42.
      This was sequenced and had an open reading frame of 269 codons encoding a
      predicted polypeptide of 28.9 kDa. The sequence showed extensive homology with
      three closely related polypeptides belonging to a family of chlorophyll a/b
      binding proteins from the light harvesting complex of photosystem I (LHCI).
      Collectively, the results suggest that MAb UB42 recognises an epitope on the type
      II chlorophyll a/b-binding protein from LHCI and that clone pUB42 encodes this
      protein.

PMID- 7727760
TI  - Nucleotide sequence of two cDNAs encoding fucoxanthin chlorophyll a/c proteins in
      the diatom Odontella sinensis.
AB  - Two cDNA clones encoding fucoxanthin chlorophyll a/c-binding proteins (FCP) in
      the diatom Odontella sinensis have been cloned and sequenced. The derived amino
      acid sequences of both clones are identical, comparison of the corresponding
      nucleic acids reveals differences only in the third codon position, suggesting a
      recent gene duplication. The derived proteins are similar to the chlorophyll a/b
      binding proteins of higher plants. The presequences for plastid import resemble
      signal sequences for cotranslational import rather than transit peptides of
      higher plants. They are very similar to the presequences of FCP proteins in the
      diatom Phaeodactylum, but different from the presequences of the gamma-subunit of
      CF0CF1 of Odontella and the peridinin chlorophyll a binding proteins (PCP) of the
      dinoflagellate Symbiodinium.

PMID- 7727761
TI  - Frequent in-frame length variations are found in the diverged simple repeat
      sequences of the protein-coding regions of two putative protein kinase genes of
      Brassica napus.
AB  - Two putative protein kinase cDNA clones were isolated from Brassica napus by
      screening with a putative protein kinase cDNA clone of Arabidopsis thaliana. The
      deduced amino acid sequences show a distinct modular composition, consisting of a
      possible protein kinase catalytic region at the amino terminus and a highly
      acidic region encoded from diverged simple repeat sequences at the carboxy
      terminus. Comparison of the nucleotide sequences encoding this acidic region
      revealed a high rate of in-frame length variation, while preserving the acidic
      characteristics. Similar variation is also found in the noncoding regions of
      these clones.

PMID- 7727762
TI  - Barley microsatellites: allele variation and mapping.
AB  - Microsatellites have developed into a powerful tool for mapping mammalian genomes
      and first reports about their use in plants have been published. A database
      search of 228 barley sequences from GenBank and EMBL was made to determine which
      simple sequence repeat (SSR) motif prevails in barley. Nearly all types of SSRs
      were found. The (A)n and (T)n SSRs occurred more often than (C)n and (G)n for n >
      or = 10. Among the dinucleotide repeats, the (CG)n SSRs occurred least often.
      Trinucleotide repeats did not occur with n > 7 and there is no correlation
      between the GC content in the trinucleotide motifs and the number of observed
      SSRs. Analysing 15 different microsatellites with 11 barleys yielded 2.1 alleles
      per microsatellite. Sequencing 25 putative microsatellites showed that the
      resolution capacity of high-quality agarose gels was sufficient to determine
      differences of only three base pairs. Five microsatellites were mapped on three
      different chromosomes of a barley RFLP map.

PMID- 7727763
TI  - Molecular pathogenesis of the chromosome 16 inversion in the M4Eo subtype of
      acute myeloid leukemia.

PMID- 7727764
TI  - CD8+ T lymphocytes in the lung of acquired immunodeficiency syndrome patients
      harbor human immunodeficiency virus type 1.
AB  - Human immunodeficiency virus-1 (HIV-1) infection of CD8+ lymphocytes has been
      described in several in vitro culture systems, but whether CD8+ cells are a
      target and also serve as a reservoir for infection in vivo as yet is unknown. We
      addressed this issue in patients with acquired immunodeficiency syndrome (AIDS)
      related lower respiratory tract chronic inflammation, which is characterized by a
      massive influx of CD8+ HIV-1-specific cytotoxic T lymphocytes (CTL). Proviral
      load in lung T lymphocytes and their subpopulations was evaluated by using the
      DNA-polymerase chain reaction (PCR) technique on cells retrieved by
      bronchoalveolar lavage. To avoid the possibility that the presence of HIV-1 DNA
      could be caused by contaminating CD4+ cells, serial dilutions of highly purified
      CD8+ cells were also analyzed by PCR. Our findings showed that lung CD8+ cells
      harbor and express HIV-1. To explore the possible mechanisms leading to pulmonary
      CD8+ lymphocyte infection, we evaluated CD4 gene expression on highly purified
      CD8+ cells by means of reverse transcriptase PCR. Despite the lack of membrane
      CD4 reactivity, we could show that CD8+ cells may express CD4 RNA. Coinfection of
      lung CD8+ cells harboring proviral HIV-1 sequences by viral agents capable of
      inducing CD4 expression (ie, HHV-6) was not detected. Our data indicate that not
      only CD4+ T lymphocytes and macrophages, but also CD8+ cells, may represent a
      target and/or a reservoir for HIV-1 in vivo, and suggest that lung CD8+
      lymphocytes could derive from precursors equipped with enough CD4 molecules to
      become HIV-1 permissive. Aside from the cell-to-cell contact between activated
      HIV-1 specific CTL and relevant targets, the infection of precursors could
      represent an additional mechanism accounting for the infection of pulmonary CD8+
      cells and their functional impairment.

PMID- 7727765
TI  - Telomerase activity in normal leukocytes and in hematologic malignancies.
AB  - Telomeres are essential for function and stability of eukaryotic chromosomes. In
      the absence of telomerase, the enzyme that synthesizes telomeric DNA, telomeres
      shorten with cell division, a process thought to contribute to cell senescence
      and the proliferative crisis of transformed cells. We reported telomere
      stabilization concomitant with detection of telomerase activity in cells
      immortalized in vitro and in ovarian carcinoma cells, and suggested that
      telomerase is essential for unlimited cell proliferation. We have now examined
      the temporal pattern of telomerase expression in selected hematologic
      malignancies. We found that, unlike other somatic tissues, peripheral, cord
      blood, and bone marrow leukocytes from normal donors expressed low levels of
      telomerase activity. In leukocytes from chronic lymphocytic leukemia (CLL)
      patients, activity was lower than in controls in early disease, and comparable
      with controls in late disease. Relative to bone marrow, telomerase activity was
      enhanced in myelodysplastic syndrome (MDS) and more significantly so in acute
      myeloid leukemia (AML). Regardless of telomerase levels, telomeres shortened with
      progression of the diseases. Our results suggest that early CLL and MDS cells
      lack an efficient mechanism of telomere maintenance and that telomerase is
      activated late in the progression of these cancers, presumably when critical
      telomere loss generates selective pressure for cell immortality.

PMID- 7727766
TI  - Frequent deletion of p16INK4a/MTS1 and p15INK4b/MTS2 in pediatric acute
      lymphoblastic leukemia.
AB  - The tandemly linked p16INK4aMTS1 and p15INK4b/MTS2 genes on chromosome 9, band
      p21 encode proteins that function as specific inhibitors of the cyclin D
      dependent kinases CDK4 and CDK6. This locus undergoes frequent bi-allelic
      deletion in human cancer cell lines, suggesting that the encoded proteins may
      function as tumor suppressors. However, more recent analysis of primary tumor
      samples has shown a much lower frequency of abnormalities affecting this region,
      raising doubt over the importance of these proteins in human malignancies.
      Hemizygous deletions and rearrangements of chromosome 9, band p21, are among the
      most frequent cytogenetic abnormalities detected in pediatric acute lymphoblastic
      leukemia (ALL), occurring in approximately 10% of cases. To determine if the
      p16INK4a/p15INK4b locus might be the target of these chromosomal lesions, we
      analyzed both genes in primary clinical samples from 43 pediatric ALL patients
      using interphase fluorescence in situ hybridization, Southern blot analysis, and
      the polymerase chain reaction. Deletions of p16INK4a/p15INK4b were identified in
      18 of 20 cases with cytogenetically observed abnormalities of 9p and 5 of 23 with
      apparently normal chromosomes 9p, with the majority containing bi-allelic
      deletions (16 homozygous/7 hemizygous). Although most homozygous deletions
      involved both genes, Southern blot analysis showed an interstitial deletion in a
      single case that was confined to p16INK4a, suggesting that p15INK4b was not the
      critical target gene in this case. Sequence analysis of both p16INK4a and
      p15INK4b in all seven cases with hemizygous deletions failed to show mutations
      within the coding regions of the retained alleles. In this select group of
      patients, deletion of p16INK4a/p15INK4b was associated with T-cell phenotype,
      nonhyperdiploid karyotype (< 50 chromosomes), and poor event-free survival. These
      findings indicate that deletion of the p16INK4a/p15INK4b locus is one of the most
      common genetic abnormalities so far detected in pediatric ALL, and that loss of
      one or more of these cell cycle kinase inhibitors is important in leukemogenesis.

PMID- 7727767
TI  - Interleukin-3 (IL-3) poor-responsive inbred mouse strains carry the identical
      deletion of a branch point in the IL-3 receptor alpha subunit gene.
AB  - Interleukin-3 (IL-3) stimulates colony formation of multiple lineages of
      hematopoietic cells. Bone marrow cells of A/J mice are nonresponsive to IL-3, and
      this observation has recently been correlated with aberrant mRNA splicing and
      impaired expression of the IL-3 receptor alpha subunit (IL-3R alpha), a binding
      component of the high-affinity receptors. We examined the IL-3R alpha gene in 27
      inbred mouse strains and found the identical mutation, a 5-bp deletion at the
      branch point of intron 7, in 10 of these mouse strains. Bone marrow cells
      isolated from these 10 mouse strains did not express IL-3R alpha on the cell
      surface and did not form colonies in response to IL-3. Because the defective IL
      3R alpha gene was found in several distantly related mouse strains, it appears to
      be a recessive allele rather than a sporadic mutation. In contrast, only 1 of 21
      wild-derived mouse strains carried the 5-bp deletion in the IL-3R alpha gene.
      This study suggests that IL-3 function is not required for normal hematopoiesis
      in mice, but the retention of the IL-3 and IL-3R system may be of some selective
      advantage in wild populations.

PMID- 7727768
TI  - Randomized study of didanosine monotherapy and combination therapy with
      zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human
      immunodeficiency virus-1 infection. AIDS Clinical Trial Groups.
AB  - To evaluate the safety and efficacy of didanosine (ddl) monotherapy and three
      different combinations of zidovudine (ZDV) and ddl in asymptomatic human
      immunodeficiency virus-1 (HIV-1) infection, we conducted an open-label, phase
      I/II study in 126 asymptomatic HIV-1-infected hemophilic and nonhemophilic
      subjects with a CD4 count of 200 to 500/mm3 stratified for prior zidovudine
      treatment and baseline CD4 count. Study arms included arm A, low-dose combination
      (ZDV 150 mg and ddl 134 mg, daily); arm B, moderate-dose combination (ZDV 300 mg
      and ddI 334 mg, daily); arm C, high-dose combination (ZDV 600 mg and ddl 500 mg,
      daily), and arm D, ddl monotherapy (ddl 500 mg, daily). Earlier, more frequent
      hepatotoxicity was experienced by hemophilic subjects (P = .008), but there were
      no differences in toxicity between treatment arms (P = .51), nor were there any
      differences in the rate of development of clinical endpoints by treatment (P =
      .41). Smaller median CD4 increases occurred over the first 12 weeks for arms A
      and D, 44/mm3 and 42/mm3, than arms B and C, 105/mm3 and 114/mm3, respectively,
      (P = .015). Hemophilia status (P = .0004) and prior ZDV experience (P = .044)
      independently predicted weaker CD4 responses during the first 12 weeks of
      treatment. Using a regression model and adjusting for hemophilia status, prior
      ZDV treatment, and baseline CD4, there was a significant reduction in
      quantitative viral load from baseline by week 12 for all treatment arms combined
      (P = .0001), with significantly lower median percent reduction for arm A (56.3%)
      than arms B, C, and D (94.6%, 98.5%, and 91.9%, respectively, P = .015). Although
      greater hepatoxicity and weaker CD4 responses occur in hemophilic subjects,
      didanosine monotherapy and combination therapy with zidovudine are safe and
      effective in asymptomatic HIV-1-infected patients.

PMID- 7727769
TI  - Unrelated bone marrow donor transplants for children with leukemia or
      myelodysplasia.
AB  - Allogeneic bone marrow transplantation is the treatment of choice for many
      childhood leukemias. The donor of choice-an HLA matched sibling-is only available
      about 30% of the time. Unrelated donors are an alternative choice. In this
      report, we describe the results of unrelated donor bone marrow transplants (BMT)
      in 50 children with leukemia (25 acute lymphoblastic leukemia [ALL], 3 acute
      myeloid leukemia [AML], 3 juvenile chronic myelogenous leukemia [JCML], 10
      chronic myeloid leukemia [CML]) or myelodysplastic syndrome (MDS; 9). The median
      age of the 31 male and 19 female patients was 9 years (range 2 to 18). Only 13
      patients were serologically matched at HLA-A, B, DR, and DQ with their donors; 6
      of these were reactive in mixed lymphocyte culture. The other 37 patients were
      mismatched for one (36 patients) or more (1 patient) HLA antigens. Pretransplant
      conditioning included cytosine arabinoside, cyclophosphamide, fractionated total
      body irradiation (TBI) (with lung, liver, and more recently, kidney shielding),
      and methylprednisolone. High-risk patients also received busulfan. Graft-versus
      host disease (GVHD) prophylaxis consisted of T-cell depletion with IgM monoclonal
      antibody T10B9 plus complement and posttransplant cyclosporine-A. Forty-nine
      patients (98%) engrafted. Median times to greater than 500 polymorphonuclear
      leukocytes (PMN)/microL and greater than 25,000 platelets/microL were 18 and 20
      days, respectively. Acute GVHD > or = grade II occurred in 16 patients (33%); 13
      (81%) of these died. Chronic GVHD developed in 30 of 40 patients at risk, but was
      extensive in only 5. Event-free survival (EFS) for all patients was 44% +/- 7%
      (median follow-up was 49 months), and overall survival was 50 +/- 7%. Patients
      with low-risk disease (ALL or AML in first or second remission and CML in chronic
      phase) had a better EFS than children with high-risk disease (60% v 34%, P =
      .07). There was no significant difference in EFS between patients who were
      serologically matched with their donors (46%) and those who were partially
      mismatched (43%) (P = .97). These data compare favorably with published reports
      for children transplanted with HLA-matched sibling donors and should encourage
      earlier consideration of unrelated donor BMT in children with leukemia or
      myelodysplasia.

PMID- 7727770
TI  - Analysis of hematopoiesis in max 41 transgenic mice that exhibit sustained
      elevations of blood granulocytes and monocytes.
AB  - An unusual mouse line (max 41) that carries an inserted transgene encoding the
      nuclear transcription factor, Max, exhibits a 50- to 60-fold elevation of blood
      neutrophils and a 10-fold elevation of blood monocytes. Analysis showed that
      these elevated levels of blood cells were sustained incrementally by a sevenfold
      increase in mature neutrophils in the bone marrow and spleen and a fourfold
      increase in granulocyte-committed progenitor cells with normal turnover times for
      mature neutrophils and monocytes in the marrow and blood. the progenitor cells
      were not autonomous and exhibited a normal quantitative responsiveness to
      stimulation in vitro by the four colony-stimulating factors. A consistent anomaly
      noted was that, when stimulated by macrophage colon-stimulating factor, max 41
      progenitor cells formed mainly granulocyte-containing colonies, rather than the
      usual macrophage colonies. The blast colony-forming cells from max 41 mice did
      not generate abnormal numbers or types of progenitor cells. The transgenic max 41
      model requires further analysis to establish the regulatory anomaly responsible
      for the excessive production of granulocytes and monocytes, but has emphasized
      that most neutrophils generated in the marrow normally never leave the organ.

PMID- 7727771
TI  - Interleukin-12 enhances peripheral hematopoiesis in vivo.
AB  - Interleukin 12(IL-12) is a cytokine that supports the proliferation and
      activation of cytotoxic T lymphocytes and natural killer (NK) cells. Recent
      evidence has suggested that IL-12 also has hematopoietic activities in vitro. We
      report studies that show that IL-12 has significant in vivo hematopoietic
      stimulating activity that includes enhancement of peripheral (splenic)
      hematopoiesis and mobilization of hematopoietic progenitor cells to the
      peripheral circulation. A single injection of recombinant murine IL-12
      significantly reduced the number of bone marrow (BM) colony-forming unit
      granulocyte-macrophage (CFU-GM) in a time-dependent manner, while concomitantly
      stimulating high proliferative potential. In contrast, splenic CFU-GM and HPP
      were increased in a time- and dose-dependent manner. Chronic administration of IL
      12 resulted in significant splenic hyperplasia with increased progenitor cells,
      increased circulating progenitor cells, and BM hypoplasia with decreased
      progenitor cells. These data show that IL-12 has significant in vivo
      hematopoietic effects that include the ability to mobilize progenitor cells to
      the peripheral circulation, which may prove to be of significant benefit for
      peripheral blood stem cell transplantation. Thus, IL-12 has potential to be an
      important agent for clinical transplantation because of its hematopoietic
      mobilization and its previously shown immune augmenting and therapeutic
      activities. This combination of hematopoietic and immune functions is unique and
      not achievable with currently used hematopoietic growth factors.

PMID- 7727772
TI  - Transforming growth factor-alpha (TGF-alpha) in human bone marrow: demonstration
      of TGF-alpha in erythroblasts and eosinophilic precursor cells and of epidermal
      growth factor receptors in blastlike cells of myelomonocytic origin.
AB  - The expression of transforming growth factor-alpha (TGF-alpha) in human
      differentiating leukemic cell lines and in circulating human eosinophils prompted
      the search for an analogous function in normal human bone marrow (BM) cells.
      Immunohistochemistry, using a monoclonal antibody directed to the mature form of
      the TGF-alpha molecule, showed TGF-alpha on the erythroblasts of normal donors.
      This novel property of erythroid cells was found on cells at all stages of
      maturation, most clearly on nucleated forms but to some extent also on
      erythrocytes within the BM. The presence of membrane-bound TGF-alpha on
      erythroblasts was confirmed by immunomagnetic cell sorting with polyclonal TGF
      alpha antibodies; the recovered cells consisted almost entirely of erythroblasts.
      Using another monoclonal antibody directed to TGF-alpha, immunohistochemistry
      showed a different pattern of positive cells including eosinophilic precursor
      cells, in accordance with earlier findings in blood eosinophils. In addition, the
      TGF-alpha immunoreactivity was shown in promyelocytes and neutrophilic
      myelocytes. The presence of epidermal growth factor (EGF) receptor mRNA in BM
      cells was demonstrated by reverse transcription polymerase chain reaction,
      whereas EGF receptor-carrying cells were recognized by immunohistochemistry,
      using polyclonal antibodies directed to the cytoplasmic part of the EGF receptor.
      The EGF receptor-positive cell constituted about 3% of the nucleated BM cell
      population. It was classified as a blastlike cell of myelomonocytic origin by
      morphologic criteria and CD68 positivity. Our results may indicate a novel
      function of TGF-alpha in erythrocytic differentiation.

PMID- 7727773
TI  - Recombinant human interleukin-1 receptor antagonist protects early myeloid
      progenitors in a murine model of cyclophosphamide-induced myelotoxicity.
AB  - Expression of hematoregulatory cytokines such as interleukin-1 (IL-1) in response
      to cytotoxic chemotherapy hastens hematopoietic recovery, but may also potentiate
      myelotoxicity if myeloid progenitors enter cell cycle before drug clearance. In
      the present study, the ability of recombinant human IL-1 receptor antagonist (IL
      1ra) to protect hematopoietic progenitors was studied in a murine model of
      cyclophosphamide (CPA)-induced myelotoxicity. CF-1 female mice received 200 mg/kg
      CPA and either 10 mg/kg IL-1ra or an equal volume of 0.05% human serum albumin
      (HSA) intraperitoneally (i.p.), followed 12 hours later by IL-1ra or HSA. CPA and
      IL-1ra increased absolute neutrophil counts (ANCs) at days 2 (P = .001) and 14 (P
      = .0025) after CPA. In IL-1ra-treated mice, colony-forming units granulocyte
      macrophage (CFU-GM)/tibia were increased twofold and threefold at days 2 (P =
      .0047) and 7 (P = .023), respectively, whereas high proliferative potential
      colony-forming cells (HPP-CFC)/tibia were decreased twofold to threefold at 8
      hours (P = .039) and 24 hours (P = .0033), but were approximately threefold
      higher than HSA-treated mice at day 7 after CPA. Coadministration of CPA and IL-1
      enhanced myelotoxicity compared with mice injected with CPA and IL-1ra or HSA. In
      vivo, IL-1ra protected HPP-CFC, but not CFU-GM, from hydroxyurea suicide after a
      single dose of CPA, suggesting that IL-1ra inhibited cycling of HPP-CFC. In
      vitro, IL-1ra did not alter proliferation of CFU-GM, but inhibited IL-1-enhanced
      proliferation of HPP-CFC. These data suggest that IL-1ra acts as an indirect
      negative regulator of hematopoiesis and protects HPP-CFC from CPA, possibly by
      inhibiting IL-1-enhanced proliferation of early myeloid progenitors.

PMID- 7727774
TI  - Abnormal subcellular distribution of myosin and talin in Wistar Furth rat
      platelets.
AB  - The roles of most cytoskeletal proteins in platelet formation and function remain
      largely undefined. We earlier detected megakaryocyte membrane blebbing and a
      unique antigenic determinant associated with a missense mutation in the
      cytoskeletal protein, talin, in an animal model of hereditary
      macrothrombocytopenia, the Wistar Furth (WF) rat, which led us to examine the
      distribution of talin and other cytoskeletal proteins in resting normal and WF
      rat platelets. In contrast to the conclusions of an earlier ultrastructural
      analysis, our biochemical and ultrastructural immunogold studies indicate a
      significant membrane-association of talin in both resting normal and WF rat
      platelets as found earlier for rat megakaryocytes. Talin was associated with
      plasma membranes, membranes of the surface-connected canalicular system, and with
      alpha-granule membranes of both normal and WF rat platelets, but as in WF
      megakaryocytes, talin was absent from the large membrane complexes of WF
      platelets. An even more striking difference was seen in the distribution of
      myosin in subcellular fractions of normal and WF rat platelets separated in
      density gradients, in which the proportion of myosin in the least dense WF rat
      platelet membrane fraction was one half that in the same normal platelet
      fraction. This difference was balanced by a fourfold increase in myosin in the
      most dense WF rat subcellular fraction, which is highly enriched for alpha
      granules. These results support our hypothesis that the platelet abnormalities of
      the WF rat are related to defects in the megakaryocyte-platelet cytoskeleton.

PMID- 7727775
TI  - Expression of the blood-clotting factor-VIII cDNA is repressed by a
      transcriptional silencer located in its coding region.
AB  - Hemophilia A is caused by a deficiency of factor-VIII procoagulant (fVIII)
      activity. The current treatment by frequent infusions of plasma-derived fVIII
      concentrates is very effective but has the risk of transmittance of blood-borne
      viruses (human immunodeficiency virus [HIV], hepatitis viruses). Use of
      recombinant DNA-derived fVIII as well as gene therapy could make hemophilia
      treatment independent of blood-derived products. So far, the problematic
      production of the fVIII protein and the low titers of the fVIII retrovirus stocks
      have prevented preclinical trials of gene therapy for hemophilia A in large
      animal models. We have initiated a study of the mechanisms that oppose efficient
      fVIII synthesis. We have established that fVIII cDNA contains sequences that
      dominantly inhibit its own expression from retroviral as well as from plasmid
      vectors. The inhibition is not caused by instability of the fVIII mRNA (t1/2, >
      or = 6 hours) but rather to repression at the level of transcription. A 305-bp
      fragment is identified that is involved in but not sufficient for repression.
      This fragment does not overlap the region recently identified by Lynch et al (Hum
      Gene Ther 4:259, 1993) as a dominant inhibitor of RNA accumulation. The
      repression is mediated by a cellular factor (or factors) and is independent of
      the orientation of the element in the transcription unit, giving the repressor
      element the hallmarks of a transcriptional silencer.

PMID- 7727776
TI  - Mutations causing coagulation factor XIII subunit A deficiency: characterization
      of the mutant proteins after expression in yeast.
AB  - We identified the mutations causing factor XIII A subunit deficiency in two
      families. Two distinct mutations were identified in the S family: the nonsense
      mutation Tyr 441-->stop in exon 11, inherited through the paternal line, and the
      missense mutation Asn 60-->Lys in exon 3, inherited through the maternal line.
      Two members of the J family were heterozygous for the previously described type 3
      A subunit. The substitution giving rise to the type 3 variant was found to be Gly
      501-->Arg in exon 12. The Asn 60-->Lys and Gly 501-->Arg mutations were
      constructed in cDNA clones and expressed in yeast (Saccharomyces cerevisiae
      AH22). Although mRNA could be detected, protein containing the Asn 60-->Lys
      substitution could not be detected, suggesting extreme instability or
      susceptibility to proteolysis. A subunits containing the Gly 501-->Arg
      substitution were expressed and found to be enzymatically active in fresh yeast
      lysates. This variant has thermal instability and lost activity during storage or
      purification. Gel filtration studies suggested that the type 3 variant assembled
      as a dimer, as do normal A subunits. The data suggest that the Gly 501-->Arg
      (Type 3 variant) would cause severe factor XIII deficiency if inherited in the
      homozygous form or as a compound heterozygote with another deleterious mutation.

PMID- 7727777
TI  - Anti-IgM induces transforming growth factor-beta sensitivity in a human B
      lymphoma cell line: inhibition of growth is associated with a downregulation of
      mutant p53.
AB  - We wished to examine the role of transforming growth factor-beta (TGF-beta) in
      the regulation of human lymphoma cell growth. The RL cell line is an
      immunoglobulin M (IgM)+, IgD+ B lymphoma cell line, which does not constitutively
      express receptors for TGF-beta, and thus has lost the ability to respond to the
      inhibitory effects of TGF-beta. We demonstrate here that anti-Ig antibodies can
      efficiently upregulate the expression of TGF-beta receptors and promote
      sensitivity to growth inhibition by TGF-beta. Furthermore, because TGF-beta has
      been shown to function in late G1 of the cell cycle, we examined the ability of
      TGF-beta to modulate two tumor suppressor proteins known to be critical
      regulators of the G1/S transition, Rb and p53. Rb is a 105- to 110-kD
      phosphoprotein, which has been shown to maintain its growth suppressive function
      when it is found in the hypophosphorylated state. Wild-type p53 is a 53-kD
      phosphoprotein that appears to be important in preventing cell-cycle progression
      and promoting apoptosis in cells with DNA damage, whereas mutant p53 can overcome
      those functions. We show here that TGF-beta treatment of phorbol myristate
      acetate (PMA) or anti-Ig-activated RL cells results in growth inhibition through
      a dual effect on Rb and mutant p53. After TGF-beta treatment, we observe a
      predominance of Rb in the hypophosphorylated, growth suppressive form. In
      addition, we show a decrease in levels of mRNA and protein for mutant p53. We
      also show that, although these changes are sufficient to halt progression through
      the cell cycle, the cells do not appear to undergo extensive programmed cell
      death following 72 hours of TGF-beta treatment. Thus, although these lymphoma
      cells maintain the capacity to be negatively growth regulated by TGF-beta, the
      ability of TGF-beta to induce apoptosis must be independently controlled.

PMID- 7727778
TI  - Interindividual conservation of T-cell receptor beta chain variable regions by
      minor histocompatibility antigen-specific HLA-A*0201-restricted cytotoxic T-cell
      clones.
AB  - Minor histocompatibility antigens (mHags) are involved in the induction of graft
      versus-host disease (GVHD) after HLA-identical bone marrow transplantation.
      Previously, we isolated a series of HLA-A*0201-restricted cytotoxic T-cell (CTL)
      clones specific for the same mHag HA-1 from peripheral blood of three unrelated
      patients who were suffering from GVHD. We have now analyzed the composition of
      the T-cell receptor (TCR) V regions of 12 of these mHag HA-1-specific HLA-A*0201
      restricted CTL clones by DNA sequencing of the alpha and beta chains. Of these 12
      clones, derived from three unrelated individuals, five independent TCR alpha V-
      and beta V-region sequences were established. The TCR alpha chains were composed
      of varying TCR alpha V and TCR alpha J genes with no obvious similarities in
      structure in the N regions. However, the TCR beta chains all used the TCR beta
      V6S9 gene segment, and showed remarkable similarities within the N-D-N regions;
      ie, three independent beta-chain sequences (originating from donors Ha and Gy)
      shared a leucine/valine amino acid pair, whereas the other two (originating from
      donors Ha and Wi) shared a serine/threonine pair, all at positions 99 and 100 of
      the TCR beta V region. In conclusion, the TCR analysis of HA-1 mHag-specific CTL
      clones has shown that the HA-1 mHag/HLA-A*0201 complex selects for highly similar
      TCR beta V regions.

PMID- 7727779
TI  - Dependency on intercellular adhesion molecule recognition and local interleukin-2
      provision in generation of an in vivo CD8+ T-cell immune response to murine
      myeloid leukemia.
AB  - The immune response to a murine myeloid leukemia (cell line C1498) was studied in
      vitro and in vivo. Natural killer (NK) cells and CD8+ cytotoxic T lymphocytes
      (CTL) were shown to lyse C1498 in vitro through the binding of leukocyte function
      antigen-1 (LFA-1) on effectors and intercellular adhesion molecule-1 (ICAM-1) and
      ICAM-2 on C1498 target cells. However, the ability of nonimmunized mice to resist
      an in vivo challenge of a low dose (10(4)) of C1498 was NK-cell, but not T-cell
      dependent. The failure of T cells to participate in the immune surveillance of a
      low leukemia burden appeared, in part, because of a lack of expansion of leukemia
      reactive CTL precursors (CTLp). Leukemia reactive CTLp frequency estimations in
      naive and leukemia bearing mice were not significantly different (range, 1:20,600
      to 1:74,000) in contrast to immunized mice (range, 1:1,400 to 1:4,400). Leukemia
      reactive CTLp could be expanded to a level that could apparently mediate in vivo
      immune surveillance of 10(5) leukemia cells by injection of irradiated leukemia
      cells intraperitoneally (IP) or subcutaneously (SC), but not intravenously (IV).
      However, IV injection of 10(5) live leukemia cells engineered to secrete
      interleukin-2 (IL-2) resulted in systemic immunity mediated primarily by CD8+ T
      cells. We conclude that NK cells can mediate immune surveillance of a low
      leukemia burden. CD8+ CTL-mediated immune surveillance can eliminate a higher
      leukemia burden than NK cells, but requires T-cell help, which can be delivered
      by local IL-2. Both NK and CTL-mediated immune surveillance of C1498 murine
      myeloid leukemia is dependent on recognition through the LFA-1:ICAM adhesion
      pathway.

PMID- 7727780
TI  - Interleukin-10 is a proliferation factor but not a differentiation factor for
      human myeloma cells.
AB  - Because interleukin-10 (IL-10) is a potent differentiation factor of human B
      cells into mature plasma cells, we investigated its effect on human malignant
      plasma cells. IL-10 did not induce any differentiation and increase in Ig
      synthesis in four human IL-6-dependent malignant plasma cell lines. However, it
      stimulated the proliferation of two of four cytokine-dependent cell lines in the
      absence of IL-6 and IL-10-dependent myeloma cell lines have been obtained. The
      myeloma cell growth activity of IL-10 was unaffected by anti-IL-6 and anti-IL-6R
      antibodies. Similarly, IL-10 stimulated (P = .001) the proliferation of freshly
      explanted myeloma cells in IL-6-deprived cultures of tumor samples from patients
      with active multiple myeloma (MM) and produced twice as many myeloma cells in
      these cultures. Again, this cytokine was unable to induce further differentiation
      (assessed by rate of Ig production) of fresh myeloma cells. A very sensitive
      enzyme-linked immunosorbent assay (ELISA; 1 pg/mL) only rarely detected IL-10 in
      the sera of MM patients (3 of 89). On the contrary, serum IL-10 was detected in
      60% of patients with plasma cell leukemia (12 of 20). These data show that IL-10
      is an IL-6-unrelated growth factor for malignant plasmablastic cells. This
      cytokine could be involved in the late phase of MM in vivo.

PMID- 7727781
TI  - Lymphoma-associated translocation t(14;18) in blood B cells of normal
      individuals.
AB  - Successive oncogenic steps are necessary to generate cancer. In many B-cell
      lymphomas, chromosomal translocations are considered to be an early oncogenic
      hit. We investigated whether the lymphoma-associated t(14;18) involving the BCL2
      oncogene can occur outside the context of malignancy. To this end, we extensively
      screened blood cells from healthy blood donors by a very sensitive seminested
      polymerase chain reaction (PCR) for breakpoint junctions at JH1-5 on 14q32 and
      the major breakpoint region of BCL2 on 18q21. In each individual, mononuclear
      cells, granulocytes, flow-sorted B cells, and T cells were separately tested in
      five to seven independently performed PCRs (in total, 0.5 x 10(6) to 1.0 x 10(6)
      cells per fraction per individual). Amplification products that hybridized with
      an internal BCL2 probe and a JH probe were sequenced. Six of nine individuals
      harbored t(14;18) breakpoints. Translocations were restricted to B cells, with an
      estimated frequency of 1 in 10(5) or less circulating B cells. In total, 23 of 51
      experiments on B cells were positive in contrast to 1 of 48 on T cells and 2 of
      47 experiments on granulocytes. Consistent with the presence of 4.7% to 13.0% B
      cells in the mononuclear cell fractions, only very few (4 of 47) tests were
      positive in these fractions. Sequence analysis showed that four of six
      individuals harbored two to five unrelated t(14;18)-carrying B-cell clones. All
      breakpoints had a structure similar to that in follicular lymphoma. We propose
      that B cells with the t(14;18) translocation are regularly generated in normal
      individuals, but that only very few cells with the translocation will acquire the
      additional oncogenic hits necessary to establish the malignant phenotype.

PMID- 7727782
TI  - Mutations of the p53 and ras genes in childhood t(1;19)-acute lymphoblastic
      leukemia.
AB  - We have investigated the alterations of p53 and ras genes including H-, K-, and N
      ras genes in 22 acute lymphoblastic leukemia (ALL) cases and five cell lines
      carrying t(1;19) by use of polymerase chain reaction (PCR)-single-strand
      conformation polymorphism (SSCP) analysis and direct sequencing. The mutations of
      the p53 gene were found in 2 of 20 t(1;19)-ALL cases at diagnosis (10%), all of 4
      cases at relapse (100%), and 4 of the 5 cell lines (80%). Four of the five
      patients who died had missense mutations at codons 49, 177, 179, and 248. In
      cases examined sequentially, one had the same point mutation at codon 179 at both
      diagnosis and relapse, and another had the same p53 gene mutation at codon 240
      both in leukemic cells at relapse and in a cell line derived at that time. The
      other case had no mutation at diagnosis but had the mutation at codon 177 at
      relapse and cell lines derived from blast cells at diagnosis, suggesting that a
      small number of leukemic cells with the p53 gene mutation at diagnosis might have
      escaped PCR-SSCP analysis. In cell lines, SCMC-L9 had three point mutations in
      the p53 gene at codons 175, 248, and 358, whereas SCMC-L10 had frame shift at
      codons 209-211. One case had a rare polymorphism at codon 11. We found only one
      mutation of the N-ras gene that was a 2-bp substitution of GGT(Gly) to GTC(Val)
      at codon 13 among 22 t(1;19)-ALL cases and five cell lines. This case showed no
      mutation of the p53 gene and has had a good course. These results suggest that in
      t(1;19)-ALL, mutations of the p53 and ras genes are infrequent at diagnosis and
      that p53 gene alterations may be associated with relapse phase or progression of
      t(1;19)-ALL.

PMID- 7727783
TI  - Interleukin-1-induced leukocyte extravasation across rat mesenteric microvessels
      is mediated by platelet-activating factor.
AB  - Although our understanding of the molecular interactions that mediate the
      adhesion of leukocytes to venular endothelial cells has greatly expanded, very
      little is known about the mechanisms that mediate the passage of leukocytes
      across the vessel wall in vivo. The aim of the present study was to investigate
      the role of endogenously formed platelet-activating factor (PAF) in the process
      of leukocyte extravasation induced by interleukin-1 (IL-1). To determine at which
      stage of emigration PAF was involved, we studied the behavior of leukocytes
      within rat mesenteric microvessels by intravital microscopy. Rats were injected
      intraperitoneally with saline, recombinant rat IL-1 beta (IL-1 beta), or the
      peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) 4 hours before the
      exteriorization of the mesenteric tissue. In animals treated with IL-1 beta there
      was a significant increase in the number of rolling and adherent leukocytes
      within venules (20- to 40-micron diameter) and in the number of extravasated
      leukocytes in the tissue. Pretreatment of rats with the PAF receptor antagonist
      UK-74,505 had no effect on the leukocyte responses of rolling and adhesion, but
      significantly inhibited the migration of the leukocytes across the vessel wall
      induced by IL-1 beta (76% inhibition). A structurally unrelated PAF antagonist,
      WEB-2170, produced the same effect (64% inhibition). However, in contrast, UK
      74,505 had no effect on the leukocyte extravasation induced by FMLP, indicating
      selectivity for the response elicited by certain mediators. These results provide
      the first line of direct evidence for the involvement of endogenously formed PAF
      in the process of leukocyte extravasation induced by IL-1 in vivo.

PMID- 7727784
TI  - Evidence for participation of vicinal dithiols in the activation sequence of the
      respiratory burst of human neutrophils.
AB  - Phenylarsine oxide (PAO) specifically forms a stable ring complex with vicinal
      dithiols that can be reversed with 2,3-dimercaptopropanol (DMP). Pretreatment of
      human neutrophils with micromolar concentrations of PAO inhibited release of
      superoxide anion (O2-) stimulated by N-formyl-methionyl-leucyl-phenylalanine
      (FMLP) or phorbol 12-myristate 13-acetate (PMA); the inhibition was reversed with
      DMP, but not with 2-mercaptoethanol. PAO did not affect O2- release in previously
      stimulated cells. PAO did not affect the FMLP-induced Ca2+ response, suggesting
      that PAO affects a postreceptor event that does not modulate the Ca2+ transient.
      Treatment of isolated membrane or cytosolic fractions with PAO did not change the
      rates of arachidonate-stimulated O2- production in a cell-free system.
      Pretreatment of unstimulated neutrophils with PAO inactivated cytosolic protein
      kinase C (PKC); the inactivation was reversed with DMP. However, PAO did not
      affect PMA-induced translocation of beta-PKC protein or reduce the PKC activity
      translocated to the membrane. PAO had no effect on tyrosine kinase activity but
      inactivated phosphotyrosine phosphatase; stimulus-induced tyrosine
      phosphorylation of several proteins was markedly enhanced. These results suggest
      that vicinal dithiols play an essential role in activation of the respiratory
      burst oxidase. Possible sites for the activity of these essential vicinal
      dithiols include PKC and the regulatory balance of tyrosine phosphatase activity
      and tyrosine phosphorylation.

PMID- 7727785
TI  - Hemolytically inactive C5b67 complex: an agonist of polymorphonuclear leukocytes.
AB  - The activity of hemolytically inactive C5b67, designated iC5b67, was evaluated as
      an agonist for functional responses of human polymorphonuclear leukocytes (PMN).
      C5b67 was formed from purified human complement components and decayed in
      phosphate-buffered saline (PBS) until it had no lytic activity for sheep
      erythrocytes in a standard assay. iC5b67, at nanomolar concentrations, stimulated
      PMN chemotaxis and Ca2+ fluxes, but inhibited superoxide production and failed to
      upregulate CR1 and CR3. There was no significant contamination of the iC5b67 with
      C5a to explain these results. Neither isolated C5b6 nor C7 alone exhibited the
      activities of iC5b67, while insolubilized anti-C7 could remove the PMN agonist
      activity from the iC5b67 preparation. Binding studies to define a specific
      receptor for iC5b67 on PMN were hampered by the very hydrophobic nature of the
      ligand. 125I-iC5b67, by contrast to hemolytically active 125I-C5b67, was unable
      to insert in erythrocytes, suggesting that iC5b67 need not insert in the PMN
      membrane to induce signaling. Two lines of evidence suggest that iC5b67 and C5a
      and FMLP share common steps in intracellular signaling (1) pretreatment of PMN
      with iC5b67 deactivates PMN for C5a- and FMLP-induced chemotaxis; and (2)
      pretreatment of PMN with pertussis toxin inhibits iC5b67-induced chemotaxis.
      Thus, iC5b67 has important effects on the activity of PMN and G-proteins and Ca2+
      are involved in the signaling.

PMID- 7727786
TI  - Association of granulocyte-macrophage colony-stimulating factor with the
      crystalloid granules of human eosinophils.
AB  - We have previously shown that normal-density human peripheral blood eosinophils
      transcribe and translate mRNA for granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and that the intracellular distribution was granular as assessed
      by light microscopy immunocytochemistry. The present study was conducted to
      confirm this apparent association between GM-CSF and the crystalloid granule
      using a subcellular fractionation method for human eosinophils and immunogold
      electron microscopy (EM). Highly purified (> 99%, by negative selection using
      anti-CD16 immunomagnetic microbeads) human peripheral blood eosinophils were
      obtained from four asthmatic subjects (not taking systemic medication),
      homogenized and density fractionated (5 x 10(7) cells/subject) on linear Nycodenz
      gradients. Twenty-four fractions were collected from each cell preparation and
      analyzed for marker enzyme activities as well as total protein. Dot blot analysis
      with specific monoclonal antibodies (MoAbs) was used to detect the eosinophil
      granule proteins major basic protein (MBP) and eosinophil cationic protein (ECP).
      An anti-CD9 MoAb was used as an eosinophil plasma membrane marker. Lactate
      dehydrogenase (LDH) was used as a cytosolic marker. Immunoreactivity for GM-CSF
      was detected by a specific enzyme-linked immunosorbent assay using a polyclonal
      antihuman GM-CSF antibody and confirmed by dot blot. GM-CSF coeluted with the
      cellular fractions containing granule markers (MBP, ECP, eosinophil peroxidase,
      hexosaminidase, and arylsulphatase), but not those containing cytoplasm (LDH+) or
      membrane (CD9+) markers. EM examination of pooled fractions associated with the
      peak of GM-CSF immunoreactivity confirmed that they contained crystalloid and
      small granules, but not plasma membrane. In addition, quantification, using
      immunogold labeling with an anti/GM-CSF MoAb, indicated preferential localization
      of gold particles over the eosinophil granule cores of intact cells. Thus, our
      results indicate that GM-CSF resides as a granule-associated, stored mediator in
      unstimulated human eosinophils.

PMID- 7727787
TI  - Identification of a major positive regulatory element located 5' to the human
      zeta-globin gene.
AB  - The function of the zeta-globin promoter was studied using a series of zeta
      globin promoter deletion constructs to drive luciferase expression in transiently
      transfected human erythroleukemia cells. The promoters were used without
      enhancers, or with enhancers derived from the beta-globin locus control region
      and the alpha-globin HS-40 enhancer. When transfected into K562 cells, which
      express zeta-globin, comparable amounts of activity were obtained from the -557
      and -417 zeta-luciferase constructs and the alpha-luciferase constructs when no
      enhancers or the alpha-globin locus enhancers were used. When the constructs were
      transfected into OCIM1 cells, which do not express zeta-globin, the zeta-globin
      promoters were at best 20% as active as the alpha-globin promoters. When
      sequences from -417 to -207 5' to the zeta-globin mRNA cap site were deleted, up
      to 95% of the zeta-globin promoter activity was lost in K562 cells. Reinsertion
      of these sequences into zeta-luciferase constructs missing the -417 to -207
      region showed that the sequences lack classical enhancer activity. Point mutation
      of a GATA-1 site at -230 reduced promoter activity by 37%. Point mutation of a
      CCACC site at -240 had no effect. Electrophoretic mobility shift assays indicated
      that the -230 GATA-1 site has a relatively low affinity for GATA-1. These
      experiments show the presence of a strong positive-acting element, located
      between -417 and -207 bp 5' to the zeta-globin mRNA cap site, is necessary for
      high-level promoter activity in K562 cells. This element requires GATA-1 and
      additional unknown factors for maximal activity.

PMID- 7727788
TI  - Murine Hertwig's anemia: premature death after normal bone marrow transplantation
      is radiation dose-dependent.
AB  - Marrow transplantation therapy in mice with heritable blood disorders usually
      leads to rapid blood cell normalization, but is sometimes followed by
      pancytopenia and premature death. This is especially true in mice with Hertwig's
      anemia (an/an). Unlike the +/+ recipients, 100% of whom survive for over a year,
      66% of the mutant mice die by 6 months posttransplantation, and the rest die soon
      thereafter. It is not clear whether premature death is due to the radiation dose
      (10 Gy) or to the fact that the F1 mutant mice receive parental-type cells known
      to induce hybrid resistance. In the present report, experiments were designed to
      determine whether the F1-an/an host is more sensitive to radiation and/or
      resistant to continued expansion of the parental-type +/+ cells. The mutant mice
      are, indeed, more sensitive to irradiation, with an LD100/30 of 7 Gy as compared
      with an LD100/30 of 10 Gy for the +/+ mice. The times of anemia onset and death
      for mutant mice implanted with +/+ cells postirradiation is also radiation dose
      dependent. Further evidence that death is due to host radiation damage rather
      than F1 hybrid resistance was provided by transplanting cells from three morbid
      10 Gy-irradiation recipients into unirradiated, anemic, stem cell-deficient, F1
      W/Wv secondary hosts. All recipients were repopulated by the original parental
      cells, were cured of their anemia, and survived for 52 weeks posttransplantation.
      The an/an mouse's heightened susceptibility to radiation damage appears to be the
      major factor in early death after transplantation therapy.

PMID- 7727789
TI  - Polymerase chain reaction detection of the BCR-ABL fusion transcript after
      allogeneic marrow transplantation for chronic myeloid leukemia: results and
      implications in 346 patients.
AB  - We studied 346 patients after bone marrow transplantation (BMT) for chronic
      myeloid leukemia (CML) for the presence of the bcr-abl transcript detected by the
      polymerase chain reaction (PCR) to understand the frequency and implication of a
      positive test. A total of 634 samples of BM and/or peripheral blood were obtained
      for PCR analysis between 3 and 192 months after BMT. A positive PCR test at 3
      months post-BMT was not statistically significantly associated with an increased
      risk of relapse compared with PCR-negative patients. However, a positive PCR
      assay at 6 months and beyond was highly associated with subsequent relapse. The
      Kaplan-Meier estimate of relapse for patients testing PCR-positive at 6 to 12
      months was 42% versus 3% for PCR-negative patients (P < .0001). The Kaplan-Meier
      estimate of survival at 4 years for the PCR-positive patients was 74% compared
      with 83% for the PCR-negative group (P = .002). Multivariable analysis indicated
      that a PCR-positive result at 6 to 12 months post-BMT, the type of BMT donor
      (allogeneic matched donor v mismatched or unrelated), and the presence of acute
      GVHD were independent risk factors for subsequent relapse. The relative risk (RR)
      for relapse for patients PCR-positive at 6 to 12 months post-BMT was 26.1 (95%
      confidence interval, 8.9 to 76.1, P < .0001). The outcome of long-term patients
      (> 36 months post-BMT) who tested PCR-positive was much better, as 15 of 59 (25%)
      tested positive for bcr-abl, but only one patient relapsed. There was a 91%
      concordance between PCR tests of simultaneously obtained BM and peripheral blood.
      These analyses show that the PCR assay of the bcr-abl fusion transcript 6 to 12
      months post-BMT is an independent predictor of subsequent relapse which provides
      an opportunity for early therapeutic intervention.

PMID- 7727790
TI  - Another unique variant pattern of intron 22 rearrangement in factor VIII gene
      seen in a hemophilia A family.

PMID- 7727791
TI  - The genotype of hepatitis C virus does not affect severity of liver disease after
      bone marrow transplantation.

PMID- 7727792
TI  - A second erythropoietin receptor subunit.

PMID- 7727793
TI  - Regulation of feeding behavior, with special reference to histamine.
AB  - Treatment with psychotropic or antiallergic drugs which block histamine H1
      receptors is known to be connected with weight gain. Also in experimental animals
      food intake is changed after manipulation of the histaminergic system, food
      intake may be decreased by various treatments with increase histaminergic
      activity and increased if histaminergic activity is reduced. Recent studies are
      reviewed illustrating the potential role of brain histaminergic system in the
      fascinating and complicated regulation of feeding.

PMID- 7727794
TI  - Are histamine H1 receptors involved in ischaemia/reperfusion injury in rat heart?
AB  - During ischaemia, there was no apparent change in malondialdehyde (MDA) content
      in rat myocardium. However, reoxygenation resulted in a significant increase in
      MDA content. The changes evoked by ischaemia and reoxygenation were significantly
      attenuated by addition of fenistil (histamine H1 receptor antagonist). Enzymatic
      antioxidant systems were not significantly modified in the different periods of
      ischaemia and after 30 min of reoxygenation. It is suggested, that maintenance of
      an adequate endogenous antioxidant reserve during ischaemia may be important in
      recovery upon reoxygenation.

PMID- 7727795
TI  - Synergistic antiplatelet action of nitric oxide (NO) with PGD2 and its metabolite
      PGJ2--relevance for cerebral circulation?
AB  - The PGI2/NO axis is well accepted for its central regulatory role in maintaining
      haemostatic balance in large arteries. Earlier findings suggest that PGD2 may
      also play a role in haemostatic regulation of human cerebral circulation. We
      therefore wondered whether PGD2 and its metabolite PGJ2 synergise in-vitro with
      NO. We approached this question using platelets of ten healthy donors and ADP as
      aggregation-inducing stimulus. Both PGD2 and PGJ2 do inhibit ADP-induced platelet
      aggregation in a dose-dependent manner. Platelet aggregation findings demonstrate
      that PGD2 and NO synergise, as does the metabolite PGJ2. Our data are indicative
      that the PGD2/NO and, in less extent, PGJ2/NO synergism might be of special
      importance for the cerebrovascular haemostatic control.

PMID- 7727796
TI  - Role of nitric oxide in gastroduodenal alkaline secretion.
AB  - This study was designed to determine the involvement of nitric oxide (NO) in
      gastric and duodenal alkaline under basal conditions and in response to exogenous
      and endogenous stimulants in conscious dogs with Heidenhain pouches and duodenal
      loops. A topical application of HCl or capsaicin increased both gastric and
      duodenal alkaline secretion. A meat meal stimulated only duodenal alkaline
      secretion while gastric secretion was not significantly changed. The NO synthase
      inhibitor, NG-nitro-L-arginine (L-NNA), significantly inhibited basal
      gastroduodenal alkaline secretion and almost completely suppressed the alkaline
      responses to food, acid or capsaicin. L-arginine given alone did not affect
      significantly basal or stimulated gastroduodenal alkaline secretion but when
      given together with L-NNA partially reversed the inhibitory effects of L-NNA on
      this secretion. For the comparison, the administration of indomethacin to
      suppress the generation of prostaglandin biosynthesis, also reduced basal and
      stimulated alkaline secretion but this reduction was relatively smaller than that
      attained by the inhibition of NO synthase with L-NNA. Luminal application of
      nocloprost, a stable prostaglandin E2 analog, and glycerin trinitrate caused
      significant increase in both gastric and duodenal alkaline secretion but these
      responses were not affected by the administration of L-NNA or indomethacin. We
      conclude that endogenous NO together with prostaglandins plays a significant role
      in secretory alkaline response of gastroduodenal mucosa to acid, food and
      capsaicin.

PMID- 7727797
TI  - Brain protein synthesis in rats with portacaval shunts.
AB  - Effects of portacaval shunts on the brain protein synthesis were studied in rats
      7, 10 and 13 weeks after the surgery. We evaluated the incorporation of [3H]
      glycine with the usage of liquid scintillation. In comparison to the controls,
      the labelled amino acid was incorporated less effectively in all the examined
      brain regions throughout the experimental period. The lowest values were observed
      10 weeks after the portacaval shunt and the drop was most distinct in the
      cerebellum (47%). The least profound changes occurred within 7 weeks after the
      surgery and the results were statistically significant only in the frontal cortex
      and the brain stem. Thirteen weeks after the shunting the incorporation of [3H]
      glycine was moderately decreased (the drop ranged between 12% and 18%) but all
      the differences were statistically significant. It seems that the inhibition of
      the brain protein synthesis may contribute to the pathogenesis of the portal
      systemic encephalopathy.

PMID- 7727798
TI  - Forms of physiological aliasing within the heart rate fluctuations by higher
      frequent respiratory movements.
AB  - In adult conscious rabbits, the respiratory frequency (RF) is almost always
      higher than half the heart rate (HR) Thus, no "classical" respiratory sinus
      arrhythmia occurred. But now, slow HR fluctuations, which were not synchronous to
      the respiratory rhythm but effected by it, occurred systematically. By
      cholinergic blockade, these slow HR fluctuations could be essentially reduced but
      not completely abolished. Up to now, this phenomenon was not be taken into
      account in the analysis of HR fluctuations. Thus misinterpretations are
      inevitable. During general anaesthesia, the RF decrease up to 2 RF < HR, and now
      classical respiratory sinus arrhythmia occurred which also could be essentially
      reduced but not completely abolished by vagal blockade. The possibilities of
      calculation of such slow HR fluctuations were shown, as those during 1/2 HR < RF
      < 3/2 HR and RF > 3/2 HR.

PMID- 7727799
TI  - Effect of work rate on cardiorespiratory response to rhythmic-static exercise.
AB  - Influence of work rate (30 and 30 rpm) on exercise hyperpnoea, respiratory
      entrainment and cardiovascular system was studied in 9 healthy men performing
      rhythmic-static exercise (RSE). Respiratory frequency (f), tidal volume (VT),
      minute ventilation (VE), heart rate (HR), stroke volume (SV), and cardiac output
      (Q) were continuously measured. RSE was performed in upright position on a
      special motor-driven cycloergometer with an intensity of 40% VO2max for 5 min.
      The subjects opposed the flywheel movement by pressing the pedal alternately with
      left and right leg. It was found that in both work rates respiratory frequency
      followed the rhythm of exercise. The increases in f (28v35 breaths/min. p < 0.05)
      were associated with decreased VT (1.3v1.0L, p < 0.05) but they did not influence
      VE which was 33 and 36 1/min (NS). Accelerations of f and VE were faster for 30
      than 60 rpm reaching respective values of 2.70v0.75 breaths/min/s (p < 0.05), and
      0.59v0.31 1/min/s (p < 0.05). Cardiac response and its kinetics were found to be
      similar for both exercise rhythms. It is concluded that breathing entrainment
      does not affect either ventilation or the cardiac response during the RSE
      exercise. Since changes in acceleration of ventilation were not accompanied by
      appropriate changes in cardiac output acceleration the cardiodynamic hypothesis
      of exercise hyperpnoea does not seem to be valid for rhythmic-static exercise.

PMID- 7727800
TI  - Effect of compound 48/80 on the thalamic mast cells, serotonin level and
      corticosterone secretion in rats.
AB  - The effect of thalamic mast cells (MCs) degranulation and serotonin liberation by
      compound 48/80 on the hypothalamic-pituitary-adrenocortical (HPA) activity,
      measured indirectly through corticosterone secretion, was investigated in
      conscious rats. All drugs were given intracerebroventricularly (icv), the
      serotonin antagonists 15 min prior to compound 48/80. One hour after
      administration, compound 48/80 (1 and 5 micrograms) caused a significant increase
      in degranulated MC number in the thalamus, from control value of 20% up to 58%,
      and a considerable rise in the serum corticosterone level, but only minor
      diminution of the thalamic serotonin content. Pretreatment with methysergide, a
      serotonin receptor antagonist, only slightly dimished the compound 48/80-induced
      corticosterone response, while pretreatment with cyproheptadine, an antagonist of
      serotonin-histamine and cholinergic-receptors, significantly decreased the
      compound 48/80-elicited corticosterone response. These results show for the first
      time that thalamic mast cells contain a very small amount of serotonin, which may
      play only a minor role in increasing the HPA activity by compound 48/80. These
      findings also suggest that other mediators liberated from mast cells by compound
      48/80 are responsible for the considerable increase in the HPA activity.

PMID- 7727801
TI  - Effect of corticotropin releasing hormone on the pituitary-adrenocortical
      activity under basal and social stress conditions.
AB  - The effect of social crowding stress on the CRH-induced hypothalamic-pituitary
      adrenocortical (HPA) responsiveness was assessed in rats crowded for 3 days, when
      the HPA response to neurotransmitter receptors stimulation was powerfully
      reduced. CRH given systemically dose-dependently increased the secretion of
      corticosterone. The increase was not affected by pretreatment with prazosin or
      propranolol, an alpha 1- or beta-adrenergic receptor antagonist, indicating the
      lack of involvement of adrenergic receptors in that stimulation. In the
      corticosterone response to CRH administered icv, a moderate involvement of
      hypothalamic alpha 1-adrenergic receptors and neuronal noradrenaline seems
      possible. The corticosterone responses to CRH given by either route to rats
      exposed to social crowding stress were identical with the responses of unstressed
      controls. Our results for the first have time shown that social crowding stress
      does not impair the HPA responsiveness to CRH stimulation.

PMID- 7727802
TI  - Use of lectins as diagnostic and therapeutic tools for cancer.
AB  - Within the past few years, lectins have become a well-established means for
      understanding varied aspects of cancer and metastasis. Evidence is now emerging
      that lectins are dynamic contributors to tumor cell recognition (surface
      markers), cell adhesion and localization, signal transduction across membranes,
      mitogenic stimulation, augmentation of host immune defense, cytotoxicity, and
      apoptosis. To advance understanding of these lectin-dependent processes, attempts
      are being made to discover new lectins that have one or more of these functions
      and to develop lectin- (or glycoconjugate-) based tools that could be used to
      home in on tumor cells. This review will summarize current research on the
      lectins and recent advances in the development of lectin-based diagnostic and
      therapeutic tools for cancer. Additionally, the future potential of lectin-based
      diagnosis and therapy is discussed.

PMID- 7727803
TI  - Microdialysis probes calibration: gradient and tissue dependent changes in no net
      flux and reverse dialysis methods.
AB  - Probe calibrations are required for accurate estimations of extracellular
      concentrations in microdialysis experiments. Several methods have been developed
      and validated for in vivo determination of dialysis membrane recovery such as the
      perfusion rate method and the No Net Flux method. In this study, the No Net Flux
      and the reverse dialysis methods were investigated. Both measure the net
      transport of drug across the dialysis membrane. The recovery was defined as R =
      (Cin - Cout)/Cin, where Cin and Cout were the concentrations of a compound in the
      perfusate and in the dialysate, respectively. First, the accuracy of the No Net
      Flux method to estimate in vivo recovery was compared in two situations:
      diffusion from the probe into the dialysis medium and diffusion from the outer
      medium into the probe. The point of no net transport was used to estimate the
      concentration surrounding the probe. Neither difference between extracellular
      concentrations (intercept values) nor difference between recoveries were
      observed. Then the reverse dialysis method was tested to estimate the relative
      loss of drug from the perfusate when the probe was placed in a drug-free medium.
      Finally comparisons of the behavior of the drug diffusion across the membrane
      under increasing gradient conditions have shown an asymptotic profile, specific
      of the tissue; blood, muscle, and adipose tissue. The faster a drug was removed
      by microvascular transport (blood > muscle > adipocytes), the higher was the
      recovery, until the perfusate concentration reached a threshold value where the
      transport process became gradient limited and no more tissue limited.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7727804
TI  - A method for frequent measurement of sedation and analgesia in sheep using the
      response to a ramped electrical stimulus.
AB  - A method for the frequent, precise measurement of the analgesic and sedative (or
      anesthetic) effects of drugs after bolus administration to sheep was developed. A
      ramped pulsed DC electrical stimulus was delivered to the hind limb of sheep via
      subcutaneous needles by use of a peripheral nerve stimulator modified to allow
      control of current ramp rate and pulse frequency, and limb withdrawal was used as
      an endpoint. The optimal stimulus pattern was found to be a pulse frequency of 20
      Hz, with a 5-sec ramp time and measurement intervals of 30 sec. The effects of a
      range of analgesic and sedative drugs on the threshold current to produce limb
      withdrawal were examined. Administration of the sedative/anesthetic drugs
      propofol and thiopentone intravenously and of the analgesic xylazine both
      intravenously and intramuscularly resulted in a reproducible dose-dependent rise
      in the threshold current required to produce limb withdrawal. Administration of
      the opioids alfentanil and pethidine produced agitation, making measurements
      unreliable. It is concluded that this device allows repeated reproducible
      measurements of analgesia and sedation to be made in sheep at a frequency
      sufficient to characterize the initial effects of analgesic and sedative drugs,
      particularly after intravenous administration.

PMID- 7727805
TI  - A urine collection system for studying the excretion of xenobiotics from
      Dungeness crabs.
AB  - A technique is described for collecting urine from the Dungeness crab, Cancer
      magister (Dana), a commercially important seafood and an indicator species of
      aquatic pollution. The technique has been modified from previously published
      methods to study the role of urinary excretion in the elimination of lipophilic
      pollutants by the Dungeness crab. The improved urine collection system uses
      chemically resistant and nonreactive materials that are better suited to
      pharmacological and toxicological studies than those used in previous methods.
      The improved method was tested by injecting a vital dye into catheterized
      Dungeness crabs and by measuring urine flows for 10 days. This technique can be
      used to determine the urinary excretion of xenobiotics and facilitate the
      characterization of chemicals and their metabolites accumulated by crabs.

PMID- 7727806
TI  - Brain microdialysis in the mouse.
AB  - Microdialysis of small brain areas of OF1 mice is shown to be feasible using the
      smallest commercially available probes (CMA/11). The brain areas studied were the
      dorsal hippocampus and nucleus accumbens. The basal concentrations of biogenic
      amine metabolites in dialysate samples were measured by HPLC with electrochemical
      detection (ED). The basal levels of MHPG, DOPAC, and HVA in the dorsal
      hippocampus were obtained immediately after probe insertion, whereas the basal 5
      HIAA concentration gradually declined. The stable levels of DOPAC, HVA, and 5
      HIAA in the nucleus accumbens were reached in 80 min. Histological controls
      showed the tract of the dialysis membrane within the studied sites. This
      procedure could allow simultaneous correlation of the neurobiochemical changes
      and pharmacological responses, and could facilitate further biochemical and
      pharmacokinetic research in the mouse.

PMID- 7727807
TI  - Combination of computerized morphonuclear and multivariate analyses to
      characterize in vitro the antineoplastic effect of alkylating agents.
AB  - The influence of 13 anticancer alkylating agents on cell proliferation, cell
      cycle parameters, and morphonuclear characteristics was monitored in vitro on
      three neoplastic cell lines. This monitoring was carried out by means of the
      digital cell image analysis of Feulgen-stained nuclei. This computer-assisted
      microscope analysis of chromatin texture made it possible to assess 15
      morphonuclear parameters. These 15 parameters were submitted to multivariate
      analyses, that is, principal-components analyses followed by the canonical
      transformation of the data. The 13 alkylating agents included four nitrogen
      mustards (chlormethine, chlorambucil, melphalan, and cyclophosphamide), two
      nitrosoureas (carmustine and lomustine), two platinum analogues (cisplatine and
      carboplatine), two ethyleneimine derivatives (thiotepa and investigational
      PE1001), one antibiotic (mitomycin C), one alkylsulfonate (busulfan), and one
      triazene (dacarbazine). The mouse MXT mammary and the human J82 and T24 bladder
      tumor cell lines were used in this study. The results show that these alkylating
      agents induced specific modifications to the chromatin pattern according to the
      subclass to which they belong. In other words, the multivariate statistical
      analyses of the 15 parameters made it possible to identify, at least partly,
      distinct subclasses of alkylating agents according to their mechanisms of action.
      As a validation of the methodology, the results also show that most of the
      alkylating agents induced an increase in the percentage of cells in the G2 phase,
      while some sometimes induced an increase in the percentage of cells in the S
      phase of the cell cycle.

PMID- 7727808
TI  - Effect of inhibitors of factor Xa or platelet adhesion, heparin, and aspirin on
      platelet deposition in an atherosclerotic rabbit model of angioplasty injury.
AB  - Acute thrombotic reocclusion and restenosis after successful coronary angioplasty
      are limitations of the procedure. Although the restenotic process is not
      completely understood, acute platelet deposition and thrombosis are considered
      important initiating mechanisms. The effort to identify pharmacologic agents
      capable of modifying acute platelet action following mechanical injury requires
      an animal model mimicking the clinical pathophysiology as closely as possible. We
      developed a model of angioplasty-induced injury in atherosclerotic rabbit femoral
      arteries. Acute 111indium-labelled platelet deposition and thrombosis were
      assessed four hours after balloon-injury in arteries subjected to prior
      endothelial damage (air desiccation) and cholesterol supplementation (one month).
      The effects of recombinant tick anticoagulant peptide (rTAP), a blood coagulation
      factor Xa (fXa) inhibitor and of recombinant leech antiplatelet protein (rLAPP),
      a platelet adhesion inhibitor, were compared to heparin (HEP) and aspirin (ASA).
      Recombinant TAP and HEP, but not rLAPP or ASA, successfully prevented thrombus
      formation and reduced platelet deposition in balloon-injured vessel segments to
      levels not significantly different from those observed in the contralateral
      atherosclerotic non-balloon-injured vessels. Therefore, this model, incorporating
      balloon catheter dilation of arteries exhibiting neointimal growth and
      atherosclerotic plaque formation, may be useful for evaluation of possible
      adjunctive therapies during angioplasty.

PMID- 7727809
TI  - Design and construction of a portable, single patient, dialysate proportioning
      machine at the University of Washington 1964-65.

PMID- 7727810
TI  - A comparison of solute clearance during continuous hemofiltration,
      hemodiafiltration, and hemodialysis using a polysulfone hemofilter.
AB  - The clearance of urea, creatinine, amino acids, vancomycin, and phenytoin was
      measured in vivo in a small animal model during continuous venovenous (CVV)
      hemofiltration, CVV hemodiafiltration, and CVV hemodialysis using a 0.25 m2
      polysulfone hemofilter. Six domestic piglets (weighing 6-11.8 kg) each received 1
      hr of all three techniques in random order. Blood flow was 50 ml/min. During CVV
      hemofiltration, filtrate production was 500 ml/hr and dialysate flow was zero.
      During CVV hemodiafiltration, filtrate production was 250 ml/hr and dialysate
      flow was 250 ml/hr. During CVV hemodialysis, net filtrate production was zero and
      dialysate flow was 500 ml/hr. The ratio of concentration of solute in filter
      effluent to concentration in whole plasma was derived for each solute during each
      of the three techniques. Mean (SD) effluent:plasma ratio for urea during CVV
      hemofiltration was 0.957 (0.038), CVV hemodiafiltration 0.876 (0.109), and CVV
      hemodialysis 0.754 (0.123); creatinine 0.942 (0.05), 0.934 (0.056), and 0.814
      (0.057); amino acids 0.996 (0.344), 0.904 (0.196), and 0.778 (0.18). For small
      unbound solutes, there is a decrease in clearance of 6% from CVV hemofiltration
      to CVV hemodiafiltration and a further decrease of 14% from hemodiafiltration to
      hemodialysis. The effluent:plasma ratio for vancomycin during CVV hemofiltration
      was 0.739 (0.082), CVV hemodiafiltration 0.643(0.063), and CVV hemodialysis 0.509
      (0.081), corresponding to a decrease of 30% from CVV hemofiltration to CVV
      hemodialysis. The effluent:plasma ratio for phenytoin was 0.302 (0.028) during
      CVV hemofiltration and was not significantly different during CVV
      hemodiafiltration or CVV hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727811
TI  - Change in inferior vena caval diameter detected by ultrasonography during and
      after hemodialysis.
AB  - The diameter of the inferior vena cava (IVC) measured by ultrasonography is used
      as a parameter to estimate right sided cardiac function and central venous
      pressure. In the current study the IVC diameter during and after hemodialysis
      (HD) was measured in chronic HD patients to explore the determinant factors of
      the diameter, and these results were obtained: 1) the maximal diameter of the IVC
      during quiet expiration (IVCe) can be a marker of circulating blood volume during
      as well as after HD, because the linear correlation between IVCe and circulating
      blood volume during and after HD were significant and almost identical; 2) the
      amount of ultrafiltration is the major determinant of IVCe during HD, because
      IVCe and circulating blood volume decreased in parallel with the amount of
      ultrafiltration during HD; and 3) since the recovery of IVCe and circulating
      blood volume, which correlated with the increase in serum protein concentration
      during HD, was almost complete while the body weight remained unchanged after HD,
      plasma refilling rather than body fluid retention was considered important in the
      recovery of IVCe and circulating blood volume after HD.

PMID- 7727812
TI  - Evaluation of an implantable ventricular assist system for humans with chronic
      refractory heart failure. Study overview. LVAS Study Group. Left Ventricular
      Assist System.
AB  - In this summary, the authors provide the background of and proposed protocol for
      a clinical evaluation of the safety and efficacy of the Novacor N120 Left
      Ventricular Assist System, sponsored by the National Heart, Lung, and Blood
      Institute. Although the clinical trial was never carried out, the protocol
      developed for this trial may be useful to other investigators considering a
      clinical trial of a circulatory support device. The protocol is summarized here
      and in five more detailed articles in this issue.

PMID- 7727813
TI  - Phosphorus removal with a variable chloride, CO2 acidified dialysate using an
      unmodified single pass system.
AB  - A method of providing dialysate was developed that used CO2 gas, rather than
      acetic acid, as an acidifying agent, allowing for the delivery of a variable
      chloride concentration. The system can be used on a standard, unmodified dialysis
      machine. The aim of the study was to test the technical feasibility of the
      dialysate delivery system and to determine whether use of the dialysate, which is
      free of acetate and can increase serum chloride concentrations above those
      normally achieved during the early phases of dialysis, could influence mass
      phosphorus removal. Using a crossover design, the effects of a standard acetate
      containing dialysate were compared with the acetate free, variable chloride
      dialysate on serum phosphorus kinetics and mass phosphorus removal in six
      hemodialysis patients. Although, as predicted, the serum chloride levels were
      higher during the initial phases of dialysis and serum bicarbonate concentrations
      were equivalent at the end of treatment, it was not possible to measure any
      differences in serum phosphorus levels during any of the time points during or
      immediately after dialysis, nor was any difference in mass phosphorus removal
      observed. Despite the presence of considerable animal evidence that acetate
      metabolism causes the intracellular shift of phosphorus, our study did not show
      any benefit, in terms of mass phosphorus removal, of an acetate free dialysate
      solution.

PMID- 7727814
TI  - A prescription model for peritoneal dialysis.
AB  - The authors have developed a mathematical model for peritoneal dialysis, based on
      the Popovich-Pyle-Moncrief approach, that is capable of predicting urea Kt/V and
      total weekly creatinine clearance for a variety of peritoneal dialysis therapies.
      This prescription model incorporates both diffusive and convective solute removal
      as well as ultrafiltration and lymphatic absorption. The primary input to the
      model is a single peritoneal equilibration test. Twenty-four hour dialysate
      collection is not required. Results from an extensive prospective clinical study
      performed with 100 patients at five dialysis centers indicate that the model is
      valid for predicting urea Kt/V and creatinine clearance for continuous ambulatory
      peritoneal dialysis and continuous cycling peritoneal dialysis. Predicted
      clearances agree with the clinical data from these patients to within an average
      difference of approximately 10%. This model promises to be a powerful tool to
      assist nephrologists in quantifying the amount of peritoneal dialysis delivered
      by a given prescription, tailoring it to individual patient needs, and
      investigating the potential efficacy of a variety of alternative therapies.

PMID- 7727815
TI  - Elimination of Staphylococcus aureus in hemodialysis patients.
AB  - Staphylococcus aureus infection and its complications are of great concern in the
      care of hemodialysis patients. Nasal contamination with S. aureus seems to be the
      main source of cutaneous contamination. The decontamination and recontamination
      of the skin of hemodialysis patients after using mupirocin nasal ointment was
      followed in a placebo control study. After 10 days of therapy with mupirocin
      nasal ointment, 25 of 33 (73%) patients were free of nasal S. aureus
      contamination in the nares (control subjects 2 of 21, 10%). At the same time, the
      prevalence of positive skin cultures for S. aureus decreased from 30 of 33 (90%)
      to 11 of 33 (33%) patients. However, during the ensuing 130 days, 14 of 25 (58%)
      patients with negative nasal cultures became recontaminated, while the skin
      became recontaminated in 11 of 22 (50%) patients. In 10 of 14 S. aureus
      recontaminated patients the original S. aureus lysotype was documented by
      specific phage reaction. Four of fourteen patients had a new S. aureus lysotype.
      Mupirocin nasal ointment eradicated S. aureus transiently in 75% of the patients
      but continuously in only 11 of 33 (30%) patients.

PMID- 7727816
TI  - Ammonia transport across hydrophobic membranes. Application to dialysate
      regeneration.
AB  - Removal of ammonia from a recirculating dialysate buffer in a portable
      hemodialysis application can be achieved by countercurrent, gas phase ammonia
      transfer across a hydrophobic membrane into an acid solution. Ammonia transfer
      fluxes as high as 0.076 mumol/sec/m2 have been achieved using a Sarns Turbo
      Membrane Oxygenator (Sarns-3M, Ann Arbor, MI) with a 1.9 m2 membrane surface area
      (0.145 mumol/sec actual rate). A simple physical model based upon ammonia
      desorption at the gas-dialysate buffer interface in a membrane pore, ammonia
      diffusion through the gas filled pore, and subsequent ammonia absorption at the
      gas/acid interface side of the pore quantitatively describes the experimental
      data. The ammonia transfer rate is most dependent upon dialysate buffer pH
      (higher pH promoting transfer rate) and ammonia concentration in the dialysate
      buffer (higher concentrations promoting transfer rate). A 500 fold improvement in
      transfer rate, however, will be required for clinical application.

PMID- 7727817
TI  - Evaluation of an implantable ventricular assist system for humans with chronic
      refractory heart failure. Designing a randomized trial.

PMID- 7727818
TI  - Evaluation of an implantable ventricular assist system for humans with chronic
      refractory heart failure. Patient selection. LVAS Study Group. Left Ventricular
      Assist System.

PMID- 7727819
TI  - Evaluation of an implantable ventricular assist system for humans with chronic
      refractory heart failure. Technical considerations. LVAS Study Group. Left
      Ventricular Assist System.

PMID- 7727820
TI  - Evaluation of an implantable ventricular assist system for humans with chronic
      refractory heart failure. Measuring quality of life.
AB  - The development of a multidimensional quality of life protocol to be used in a
      clinical trial of an LVAS was presented. The complexity of the new LVAS
      technology being evaluated added a unique dimension for HQL assessment. The
      rationale and procedures used in developing this protocol were described.
      Although we have elucidated the development of a protocol for a specific clinical
      trial, the principles and procedures employed are widely applicable. To
      summarize, these procedures are as follows: 1. Determine what quality of life
      domains are important to measure. This decision should be based upon the domains
      expected to be affected by treatment, those expected to change as a result of the
      natural course of the disease or condition, and those that may be affected by
      changes in the primary domains. 2. Once the domains are selected, identify
      specific measures for these domains. Where possible, the measures chosen should
      be standardized, well validated, and appropriate to the study population.
      Instrument length and mode of administration are additional considerations. 3.
      Consider any unique aspects of the study population or intervention and develop
      specific questions to address them. 4. Identify and measure important variables
      that may moderate or influence quality of life. 5. Test the protocol on an
      appropriate population for length, flow, and ease of administration. Copies of
      the complete HQL protocol are available by writing to: Dr. Nancy Avis, New
      England Research Institute, 9 Galen Street, Watertown, MA 02172.

PMID- 7727821
TI  - Evaluation of an implantable ventricular assist system for humans with chronic
      refractory heart failure. Device explant protocol.
AB  - An explant protocol was developed to investigate the effects of implantation of a
      left ventricular assist system (LVAS) manufactured by Novacor Division, Baxter
      Healthcare Corporation on the function of end organs (such as the brain, the
      kidney, the liver), with particular interest in examining possible complications
      due to LVAS support. Emphasis was placed on an analysis at the time of device
      removal and/or autopsy of 1) the local LVAS-host interface; 2) remote
      cardiovascular and end-organ effects; and 3) the impact of chronic circulatory
      support on the native heart. To accomplish these objectives, tissue and device
      samples must be obtained in an appropriate fashion to ensure photographic
      documentation, microscopic examination, microbiologic and biochemical assays, and
      compliance with regulatory and manufacturer requirements. This article describes
      the techniques and protocol that were proposed to ensure the quality of device
      explant and tissue analysis.

PMID- 7727822
TI  - The dawn of biotechnology in artificial organs.

PMID- 7727823
TI  - Localization of atherosclerosis in arterial junctions. Concentration distribution
      of low density lipoproteins at the luminal surface in regions of disturbed flow.
AB  - To investigate the role of fluid mechanical factors in atherogenesis and
      anastomotic intimal hyperplasia, the effect of blood flow on the transfer of low
      density lipoproteins from flowing blood to the luminal surface was studied
      theoretically using a two dimensional T-junction model. The flow fields in the
      junction were obtained by solving the Navier-Stokes equations numerically and the
      concentration distribution of low density lipoproteins at the luminal surface was
      determined using a finite difference analysis. The transfer of low density
      lipoproteins from flowing blood to the surface of the vessel wall was greatly
      enhanced in the two regions of disturbed flow, one in the main vessel, the other
      in the subsidiary vessel. The highest concentration of low density lipoproteins
      on the inner surface of the vessel wall was predicted to occur in the areas of
      the reattachment points. The slower the recirculation flow, the higher the lipid
      accumulation at the luminal surface in the disturbed flow regions and the wider
      the highly concentrated low density lipoprotein area. In summary, the authors'
      mathematical model predicts that locally disturbed blood flows at arterial
      bifurcations and surgically created junctions provide favorable conditions for
      the accumulation of atherogenic substances at the luminal surface, thus
      increasing the potential for lipid infiltration into the vessel wall.

PMID- 7727824
TI  - A novel method for the continuous measurement of endotoxin concentration.
AB  - Conventional limulus amebocyte lysate tests involved procedures to prevent
      contamination by atmospheric endotoxins. To address this problem, the authors
      have proposed a technique in which the sampling, reagent mixing, and reaction
      steps are carried out consecutively in a single tube. Since reagents do not come
      in contact with the atmosphere, the new technique promises stable determination
      of the concentration of endotoxins in dialysate fluid. An aqueous solution of
      endotoxin simulating dialysate fluid was sampled in a silicone rubber tube from a
      sterile infusion bag, then mixed with an indicator in the same tube. After
      reaction at 310 K, measurements were made of light absorbance at 405 nm and its
      linearity with endotoxin concentration was determined. Results showed a high
      degree of linearity (correlation coefficient of not less than 0.99) at endotoxin
      concentrations of 0-15 pg/ml. The time for the reaction was shortened to 12 min,
      in which case the response time was 15 min. It is suggested that this new test
      for determining endotoxin concentration using limulus amebocyte lysate reagent,
      in which all three steps--sampling, mixing, and reaction--proceed continuously in
      a single tube, offers higher reliability, greater ease of operation, and shorter
      response time than conventional tests.

PMID- 7727825
TI  - Crosslinkage of collagen by polyglycidyl ethers.
AB  - Calcification is the principal cause of failure of glutaraldehyde treated
      bioprosthetic heart valves. This article reports the crosslinkage of several
      polyglycidyl ethers. Calcification of yak pericardium with polyglycidyl ethers
      was significantly decreased compared with that crosslinked with glutaraldehyde.
      The process of calcification of crosslinked yak pericardium was studied using 21
      day subdermal implants in rats. The uptake of calcium with ethane diglycidyl
      ether was reduced (0.57 +/- 0.19 vs 4.28 +/- 1.62 micrograms/mg) over that with
      glutaraldehyde. Four polyglycidyl ethers were developed and compared. The best
      compound for raising the shrinkage temperature was the shortest chain compound
      without steric hindrance. In the polyglycidyl ether process, a suitable amount of
      alcohol was necessary to promote crosslinking; the catalyst, 2, 4, 6 -tris
      (dimethyl aminomethyl) phenol (TDAMP) and salicylic acid, were not favorable for
      long-term treatment of tissues because of the unnecessarily deep dyeing of the
      tissue, in addition to raising the shrinkage temperature. Unlike glutaraldehyde
      treatment, which reacts with lysine, polyglycidyl ether treated tissues
      maintained flexibility of the pericardial tissue, while binding amino acids such
      as lysine, methionine, tyrosine, aspartic acid and glutamic acid. The authors
      conclude that the ethane diglycidyl ether process combined with formaldehyde
      would further raise the shrinkage temperature from 78 degrees C to 87.5 degrees C
      and sustain it above 80 degrees C. Reverse treatment was not as effective.
      Compared with glutaraldehyde, polyglycidyl ether treatment renders tissue more
      flexible, increases the thermal stability of collagen, and decreases the
      incidence of calcification in vivo.

PMID- 7727826
TI  - New algorithm of intra aortic balloon pumping in patients with atrial
      fibrillation.
AB  - Intra aortic balloon pumps have been operated inaccurately when used in patients
      with atrial fibrillation. In 36 pre-operative cardiac surgical patients with
      atrial fibrillation, the interval between the R wave of the electrocardiogram and
      the dicrotic notch (R-DCN interval) of the aortic pressure waveform showed
      significant correlation with the preceding R-R interval by second degree
      polynomial curves (0.53 < r2 < 0.74, p < 0.01). Based on these results a new
      algorithm for atrial fibrillation was designed. During brief off periods of the
      intra-aortic balloon pump in atrial fibrillation, electrocardiograms and aortic
      pressure waveforms were simultaneously recorded and analyzed to obtain a second
      degree polynomial curve between the preceding R-R and R-DCN intervals. The
      precise timing of balloon inflation was controlled using the equation in response
      to the preceding R-R interval. This new algorithm showed the smallest time lags
      (SD = 8.5 msec) when compared to other existing algorithms (the Kontron model-10,
      53.49 msec; the Aries Medical model-700, 43.69 msec; the Datascope system-90,
      25.98 msec; the Mansfield 3000, 19.65 msec; and the Kontron K-2000, 14.89 msec)
      in mock simulation driving using data obtained from clinically recorded
      waveforms.

PMID- 7727827
TI  - Deterministic chaos in the hemodynamics of an artificial heart.
AB  - To analyze the hemodynamic parameters during prosthetic circulation as an entity,
      non linear mathematical techniques were used. To compare natural and prosthetic
      circulation, two pneumatically actuated ventricular assist devices were implanted
      as biventricular bypasses in chronic animal experiments using adult goats to
      consitute the biventricular bypass complete prosthetic circulation model with
      ventricular fibrillation. After implantation, these goats were placed in a cage
      and extubated after waking. All hemodynamic parameters with the natural
      circulation without biventricular bypass pumping, and the artificial circulation
      with biventricular bypass pumping under ventricular fibrillation were recorded
      under awake conditions. By the use of a non linear mathematical technique, the
      arterial blood pressure waveform was embedded into a four dimensional phase space
      and projected into three dimensional phase space. The Lyapunov numeric method is
      used as an adjunct to the graphic analysis of the state space. A phase portrait
      of the attractor showed a high dimension complex structure, with three
      dimensional solid torus suggesting deterministic chaos during natural
      circulation. However, a simple attractor, such as a limit cycle attractor, was
      observed during artificial circulation. Positive Lyapunov exponents during
      artificial circulation suggest the lower dimensional chaotic system. Thus,
      hemodynamic parameters during prosthetic circulation must be carefully controlled
      when unexpected stimuli are fed from outside.

PMID- 7727828
TI  - In vitro pulsatile flow evaluation of a stentless porcine aortic bioprosthesis.
AB  - Suboptimal hemodynamic performance, tissue calcification, and limitation in long
      term durability have been encountered clinically after aortic valve replacement
      with currently available bioprostheses. It is believed that some of these
      problems may be caused, directly or indirectly, by the stents of the
      bioprostheses. To address these deficiencies, the authors undertook the
      development of the Edwards Prima Stentless Bioprosthesis. This study was designed
      to evaluate the hemodynamic performance of the Edwards Prima Stentless
      Bioprosthesis in a pulse duplicator system. The stented Carpentier-Edwards
      Porcine Bioprosthesis (Baxter Healthcare Corp., Irvine, CA), which has been used
      in United States clinics for more than 10 years, was used as a control device.
      The flow fields in the vicinity of the test bioprostheses were inspected with
      color Doppler flow mapping. The transvalvular pressure gradients were measured
      invasively with a catheter and calculated with the Doppler determined velocity
      using a simplified Bernoulli equation. Additionally, the leakage volumes were
      determined with an electromagnetic flowmeter. In the Doppler flow mapping study,
      during systole, a central flow was observed distal to the stentless and stented
      bioprostheses. The central flow distal to the stentless bioprosthesis was broader
      than that observed distal to its stented counterpart. During diastole, no
      regurgitation was detected by color Doppler flow mapping in either the stentless
      or stented groups. The Doppler determined transvalvular pressure gradients
      correlated well with those measured by catheter (r = 0.990). Moreover, it was
      learned that the transvalvular pressure gradients of the stentless bioprosthesis
      were less than those of its stented counterpart, especially for the smaller
      sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7727829
TI  - Evaluation of the fibrinolytic system in calves implanted with an artificial
      heart and ventricular assist device.
AB  - Thromboembolism is a serious complication of prolonged use of intracirculatory
      devices such as total artificial hearts (TAH) and ventricular assist devices. The
      authors have evaluated alteration in the hemostatic system associated with long
      term use of TAH and ventricular assist devices. This article reports results of a
      prospective evaluation of the fibrinolytic system in four calves implanted with
      TAHs and four with ventricular assist devices. Blood fibrinolytic activity
      measured with a solid phase radiometric assay was elevated in two of four TAH
      calves; plasma plasminogen activity was increased in three. Plasma plasminogen
      activator activity was undetectable (normal) in all animals. Slight to moderate
      hypofibrinogenemia was noted in all TAH calves. Calves implanted with a left
      ventricular assist device had mostly normal blood fibrinolytic activity,
      fibrinogen, and plasminogen levels. Fibrinogen survival was measured in two
      calves with ventricular assist devices and three with TAH and was in the normal
      range in all of these animals. No significant thrombotic lesions were noted at
      autopsy in five calves that died or were electively killed. These observations
      suggest enhanced activation of the fibrinolytic system in some calves implanted
      with a TAH. This may offer a measure of protection against thrombosis in some
      animals.

PMID- 7727830
TI  - Elevated procollagen type I carboxyterminal propeptide production in cultured
      scleroderma fibroblasts.
AB  - BACKGROUND: We recently reported that the serum concentration of procollagen type
      I carboxyterminal propeptide (P1CP) in patients with systemic sclereosis (SSc)
      was elevated. In the present study, we investigated collagen metabolism in in
      vitro cultured scleroderma fibroblasts by measuring P1CP levels in the culture
      medium. METHODS AND RESULTS: Spontaneous P1CP production was 4.2 times higher in
      fibroblast cultures from patients with SSc (n = 11) than in those from healthy
      controls (n = 10). P1CP production in fibroblasts derived from diffuse cutaneous
      SSc patients was significantly greater than that from limited cutaneous SSc
      patients. The serum P1CP level in SSc patients was correlated with the P1CP
      production of cultured fibroblasts (r = 0.815, p < 0.005). Transforming growth
      factor beta increased P1CP production, and gamma-interferon decreased P1CP
      production similarly in both SSc and normal fibroblasts. In contrast, histamine
      dihydrochloride increased P1CP production only in SSc fibroblasts but not in
      controls. CONCLUSION: These findings suggest that P1CP production in SSc
      fibroblasts is relevant to in vivo collagen synthesis in SSc patients.

PMID- 7727831
TI  - Investigation of the personality structure in patients with vitiligo and a
      possible association with impaired catecholamine metabolism.
AB  - BACKGROUND: Patients with vitiligo show an increased beta 2-adrenoceptor density
      in differentiating vitiliginous keratinocytes correlating with a defective
      extracellular calcium uptake. Thirty-one percent of the patients present
      increased norepinephrine levels in their urine and 98% in their plasma.
      OBJECTIVE: The aim of this study was to find out whether these patients may: (a)
      have a characteristic personality structure and/or (b) show an increased stress
      sensitivity towards physical/environmental/hormonal changes in association with a
      defective catecholamine metabolism. METHODS AND RESULTS: The investigation
      included a randomized group of 117 patients with vitiligo (89 female, 28 male).
      Catecholamines were determined in plasma in a random sample of the total group (n
      = 30, M/F = 10/20). Norepinephrine levels in plasma were significantly higher
      compared to controls, whereas epinephrine was within the normal range. No
      specific personality pattern was found although divergencies from the normal
      healthy control were observed in 5 out of 12 personality dimensions. Moderate to
      intolerable disfigurement and psychological disturbance were stated by 75% of the
      patients. Evaluation of the educational status revealed that 26.5% of the
      patients graduated successfully from university compared to 8.4% in the normal
      population. CONCLUSION: The results of this study suggest a possible link between
      catecholamine-based stress and a genetic susceptibility to the onset/progression
      of this depigmentation disorder.

PMID- 7727832
TI  - Factor XIIIa-related antigen immunoreactivity of fungal cell wall: a biologically
      relevant feature?
AB  - BACKGROUND: A positive immunoreactivity of fungal walls for factor XIIIa has been
      recently described. Factor XIIIa is a transglutaminase involved in the formation
      of covalent peptide bounds between some specific proteins. OBJECTIVE: The purpose
      of this study was to explore by experimental approaches the meaning of that
      immunoreactivity. METHODS: The presence of a factor XIIIa-related antigen (FXIIIa
      RA) was searched on fungi by using immunohistochemistry. We studied fungi growing
      on agar plates, stratum corneum, artificial skin as well was in clinical
      conditions. RESULTS: Our present studies show that the cell wall of some
      pathogenic fungi express FXIIIa RA immunoreactivity. This was found in clinical
      infections, as well as in selected in vitro situations including cultures on
      stratum corneum and on reconstructed skin. CONCLUSION: The distinct intensity and
      pattern of FXIIIa RA immunoreactivity may suggest a relationship between this
      biological marker and the pathogenicity of fungi.

PMID- 7727833
TI  - Cutaneous T-cell lymphoma arising from parakeratosis variegata: long-term
      observation with monitoring of T-cell receptor gene rearrangements.
AB  - BACKGROUND: Parakeratosis variegata is a rare skin disease first described in
      1890. Even today, the disease entity remains confusing because various names
      indicating similar skin conditions have been used. Several cases of parakeratosis
      variegata have been reported to develop into cutaneous T-cell lymphoma, but there
      have been no reports describing the occurrence of lymphoma after a long-term
      follow-up period nor have T-cell receptor gene rearrangements been monitored in
      this disease. OBJECTIVE: Our purpose was to determine whether parakeratosis
      variegata (long-standing premycotic condition) can develop into cutaneous T-cell
      lymphoma. METHODS: We analyzed skin specimens from a patient with a 33-year
      history of parakeratosis variegata by Southern blotting using a T-cell receptor
      gene probe. RESULTS: We could detect apparent rearranged bands of T-cell receptor
      gene in the skin specimens taken in 1993 in contrast to the DNA analysis in 1988
      which featured no such rearranged band. CONCLUSION: This case represents a
      critical stage of parakeratosis variegata converting to lymphoma. Our results
      indicate that parakeratosis variegata generated monoclonality of T cells in its
      chronic course.

PMID- 7727834
TI  - Photopheresis in the red man or pre-Sezary syndrome.
AB  - BACKGROUND: The beneficial effect of extracorporeal photochemotherapy has clearly
      been established for patients with cutaneous T-cell lymphoma with Sezary's
      syndrome. But this treatment has not been used in the red man syndrome or pre
      Sezary syndrome. Some of these patients do not respond sufficiently or do not
      tolerate other therapies. OBJECTIVE: The purpose of this open study was to
      evaluate the clinical efficacy of photopheresis in this group of patients.
      METHODS: Seven patients with the red man syndrome were treated on 2 consecutive
      days every 4 weeks for 6-22 months. Six had been on systemic steroids and 3 had
      also received retinoids without sufficient effects. All were initially treated
      with topical nitrogen mustard but no longer tolerated this treatment. RESULTS:
      All signs of erythroderma disappeared in 6 of the 7 patients. All systemic
      therapy could be discontinued in all but 2 patients. No side effects were
      observed. CONCLUSION: Photopheresis may be an effective alternative treatment for
      this group of patients, when other types of therapy have failed.

PMID- 7727835
TI  - Validation of an in vivo wound healing model for the quantification of
      pharmacological effects on epidermal regeneration.
AB  - BACKGROUND: Non-invasive assessment methods such as measurement of the
      transepidermal water loss (TEWL) allow a continuous follow-up of cutaneous
      processes with impairment of the epidermal barrier function. OBJECTIVE: The aim
      of the trial was to establish an in vivo model for the assessment of drug effects
      on epidermal regeneration. METHODS: Twenty healthy volunteers were included in
      this double-blind randomized trial. After setting four suction blisters on the
      volar aspect of the forearm, the epidermis was removed to create a standardized
      subepidermal wound. Thereafter the wounds were treated topically for 6 h daily
      during 14 days. The following treatments were to be compared: a clobetasol 17
      propionate preparation under occlusion, a corticoid-free cream under occlusion,
      no treatment and occlusion (aluminium chamber), no treatment and no occlusion.
      Daily measurement of TEWL above the wounds was performed. RESULTS: The 0.05%
      clobetasol 17-propionate preparation caused a dramatic delay in TEWL decrease,
      whereby the untreated unoccluded field showed a continuous decrease over the
      observed period of 14 days. Occlusion and corticoid-free treatment led to a weak
      but significant delay of TEWL decrease when compared to the untreated unoccluded
      test field. CONCLUSION: This model seems to describe re-epithelialization in a
      reliable manner and can be used for in vivo assessment of drug effects on
      migrating and proliferating epithelial cells.

PMID- 7727836
TI  - Treatment of verrucous carcinoma with recombinant alfa-interferon.
AB  - BACKGROUND: Verrucous carcinoma is an uncommon neoplasm whose medical treatment
      is not well defined. OBJECTIVE: We report the clinical effects of recombinant
      alpha-interferon (IFN) with varying dispensing routes on the tumor size in 3
      patients exhibiting three different subtypes of verrucous carcinoma.
      OBSERVATIONS: In case 1, an oral florid papillomatosis of the upper gingiva, a
      stabilization of the lesion size was observed after the administration of a
      cumulative dose of 45 million IU of IFN alfa-2b. The patient died after
      discontinuation of the treatment due to hepatic toxicity. In case 2, a giant
      condyloma acuminatum of the penis, treatment with a cumulative dose of 522
      million IU of IFN alfa-2a first resulted in stabilization of the disease, and no
      evidence of recurrence was observed after surgical treatment. In case 3, a
      verrucous carcinoma of the leg, a mild decrease in lesion size was observed after
      the administration of a cumulative dose of 174 million IU. Surgery was finally
      required. CONCLUSION: In reducing the growth of the tumor, treatment by IFN
      appears to be an adjuvant therapy of verrucous carcinoma, but it never prevents
      surgery or death.

PMID- 7727837
TI  - Necrotizing fasciitis due to Pasteurella multocida infection.
AB  - Necrotizing fasciitis is a potentially fatal clinical disease caused by infection
      with various bacteria in addition to streptococci, which are common causative
      agents. We report on a rare case of this disease in association with Pasteurella
      multocida infection. A 58-year-old man had systemic features of shock after a 15
      hour history of a painful swelling on the right lower leg. The swelling led to
      skin blistering and necrosis from which P. multocida was isolated. Those lesions
      progressed rapidly. The patient also had a history of chronic liver injury as
      described in previous reports.

PMID- 7727838
TI  - Stiff skin syndrome: a case report and review of the literature.
AB  - Stiff skin syndrome (SSS) is a rare disorder characterized by stony-hard skin,
      limited joint mobility and mild hypertrichosis. We present a severe case in a 4
      year-old boy. In addition to the clinical and histological features of SSS, our
      patient also had muscle and bone involvement along with pyloric stenosis, gastro
      esophageal reflux, inguinal hernias and atopic dermatitis. We highlight the
      complexity of this case and the diagnostic approach to patients with this
      disorder. We also review and summarize the 24 cases previously reported in the
      literature.

PMID- 7727839
TI  - Lichen planus presenting with erythema-multiforme-like bullous lesions in a
      patient with systemic scleroderma.
AB  - A patient with systemic scleroderma is described who developed a cutaneous
      eruption of papules and vesicobullae. Over time, the latter turned into papules.
      The histopathological and immunofluorescence features of the papular lesions were
      unequivocally those of lichen planus, while those of the bullous lesions reminded
      of erythema multiforme. Histologically, erythema multiforme shares common
      features with lichenoid reactions, such as necrotic keratinocytes. Our case
      suggests that erythema multiforme and lichen planus may coexist or succeed each
      other as different stereotype immune reactions against the same antigen(s) within
      the epidermis.

PMID- 7727840
TI  - Sweet's syndrome with myelofibrosis and leukemia: partial response to interferon.
AB  - Sweet's syndrome with malignancy or acute neutrophilic dermatosis (AND) is an
      unusual cutaneous disorder seen most commonly in association with acute
      myelogenous leukemia. A large majority of patients with AND and malignancy have
      neoplasms of hematopoietic, plasma cell or lymphoid nature. The patient reported
      here had myelofibrosis, chronic myelogenous leukemia and Sweet's syndrome. The
      individual lesions responded to intralesional interferon-alpha 2, which has not
      to our knowledge been reported previously. This result, however, was not as great
      as the response of AND to intralesional steroid injections.

PMID- 7727841
TI  - Eosinophilic pustular folliculitis in three atopic children with hypersensitivity
      to Dermatophagoides pteronyssinus.
AB  - Three children will be described who present recurrent episodes of pruritic
      papulopustular follicular lesions on the face, the extremities and the trunk. The
      episodes lasted for 1-3 months with intermittent remission. Each flare was
      accompanied by hypereosinophilia and an increased total IgE titer. RAST and prick
      tests were positive for Dermatophagoides pteronyssinus (DPT). Laboratory tests
      disclosed no infectious or parasitic etiology. Histological examination showed
      eosinophilic pustular folliculitis (EPF) in each of the 3 cases. The lesions
      responded well to topical corticosteroids. The aim of this article is to
      underline the importance of hypersensitivity reactions (in these particular cases
      to DPT) in the pathogenesis of EPF.

PMID- 7727842
TI  - Giant acquired fibrokeratoma of the nail bed.
AB  - A 41-year-old Japanese woman presented with a red, elastically hard, hook-shaped
      hyperkeratotic large tumor on her right third toe, which originated from the nail
      bed. The final diagnosis was acquired fibrokeratoma. Our case is remarkable,
      because acquired fibrokeratoma is usually relatively small and does not involve
      the nails.

PMID- 7727843
TI  - The sunbed suntan sacroscapular sparing sign.

PMID- 7727844
TI  - Chronic hepatitis C infection and psoriasis.

PMID- 7727845
TI  - Darier-White syndrome and cyclosporin.

PMID- 7727846
TI  - Toxic epidermal necrolysis related to ketoprofen.

PMID- 7727847
TI  - Chronic recurrent acyclovir-resistant genital herpes in an immunocompetent
      patient.

PMID- 7727848
TI  - Photopheresis and the red man syndrome.

PMID- 7727849
TI  - Digital image analysis of microcomedones.
AB  - OBJECTIVE: Developing a technique for quantifying the number and size of
      follicular casts and microcomedones. BACKGROUND: There is no human testing that
      is validated up to now to predict comedogenesis and comedolysis following topical
      applications of drugs or cosmetics. DESIGN: Evaluations are performed by digital
      image analysis of cyanoacrylate follicular biopsies. The effects of two topical
      products are compared. RESULTS: Microcomedogenesis was disclosed after a 2-month
      period of application of a cosmetic product aimed at treating acne.
      Microcomedolysis occurred following usage of a topical preparation containing
      benzoyl peroxide 5% and miconazole nitrate 2%. CONCLUSION: Digital image analysis
      of skin surface biopsies is a sensitive method documenting microcomedo formation
      and dissolution.

PMID- 7727850
TI  - [Primary malignant brain tumors].

PMID- 7727851
TI  - [Non small-cell bronchial cancer].

PMID- 7727852
TI  - [Colorectal cancer].

PMID- 7727853
TI  - [Malignant melanoma].

PMID- 7727854
TI  - [Multiple drug resistance to anticancer medications].

PMID- 7727855
TI  - [Drug resistance, oncogenes, and anti-oncogenes in epithelial tumors].
AB  - Twenty four squamous cell carcinomas of the head and neck (HNSCC) of stage II to
      IV were evaluated for the expression of potential markers such as oncogenes and
      tumor suppressor genes in drug-resistance behavior. We have analysed the c-myc, c
      jun, c-raf and N-ras and p53 expression in total RNA preparation from tumor
      biopsies obtained before treatment. The patients underwent chemotherapy including
      5-fluorouracil and cisplatinum. No significant differences in c-raf and N-ras
      expression were found in responding or resistant patients. However, resistance to
      chemotherapy was associated with low expression of c-myc (P < 0.025) or high
      expression of c-jun (P < 0.001). In addition, p53 mRNA pre-therapeutic level was
      increased in unresponsive patients to chemotherapy (P < 0.05). Therefore,
      analysis of the expression of c-myc, c-jun oncogenes and p53 tumor suppressor
      gene in tumor cells before initiation of therapy may define a subset of patients
      with potentially better prognosis.

PMID- 7727856
TI  - [From the research laboratory to the clinical laboratory: reflections on the
      transfer of technology about drug resistance].
AB  - The routine transference of technology necessitates a credibility which must rest
      upon the definition of the parameters which are to be measured and upon a
      complete evaluation which allows one to anticipate the transference. Both aspects
      of chemotherapy are envisaged the qualitative and the quantitative aspects using
      several examples.

PMID- 7727857
TI  - [Resistance and resistances].
AB  - Drug resistance is a frequent clinical event, induced by more than one mechanism.
      It is intrinsic and/or acquired by tumoral cell population. But the failure of
      chemotherapy is also associated to intratumoral drug incorporation and altered
      drug and/or cell metabolism. Prevention of drug resistance needs integration of
      pharmacokinetic, biochemical and pathological characteristics of tumoral cell
      population.

PMID- 7727858
TI  - [Drug resistance: from research to clinical trial. XIth meeting of Grenobloises
      de Cancerologie. 24-25 March 1994].

PMID- 7727859
TI  - [Drug resistance of human tumors: from the laboratory to the clinic].
AB  - Chemoresistance of human malignant tumors causes the failure of anticancer agents
      for most carcinomas and for some hematological tumors. It is due to bad
      pharmacological conditions and also to resistance mechanisms at the cellular and
      at the molecular level. The identification and the comprehension of these
      resistance mechanisms as well as the possibility of circumventing them or
      preventing them might be responsible of a therapeutic progress in the next few
      years. However, at the present time, methodological process of identification and
      quantification of these mechanisms persist and the preliminary results of
      clinical trials with revertant drugs are still weak.

PMID- 7727860
TI  - Chemoresistance in the clinic: overview 1994.
AB  - One of the most exciting areas in clinical oncology today is the translation of
      laboratory research in drug resistance into therapeutic tools to improve
      responses to antineoplastic drugs. Two areas of investigation are currently under
      study in both the laboratory and clinic: reversal of gluthathione-mediated
      resistance and of P-glycoprotein mediated resistance. Studies are directed toward
      determining the role of the resistance mechanism in cancer, and toward its
      reversal. Increased expression of gluthathione and related enzymes, such as the
      gluthathione S-transferases, has been shown in human tumor samples. Phase I
      clinical studies with buthionine sulfoxime (BSO) have shown that gluthathione can
      be depleted without undue normal tissue toxicity. Now, clinical studies are
      underway evaluating the ability of BSO to enhance the efficacy of chemotherapy.
      Expression of P-glycoprotein has been described in human tumors, with increased
      levels observed after natural product chemotherapy in some malignancies. Studies
      with P-glycoprotein antagonists have been conducted in leukemia, lymphoma,
      multiple myeloma and in a variety of advanced malignancies. These studies have
      employed "first generation" antagonists such as verapamil and cyclosporine which
      were toxic at concentrations needed to block P-glycoprotein. Currently, studies
      are underway with "second generation" antagonists such as the dex stereoisomer of
      verapamil and the cyclosporine analogue, PSC 833. These agents may help determine
      the role of P-glycoprotein in clinical drug resistance. Together, these studies
      are aimed toward improving chemotherapeutic sensitivity in human cancer.

PMID- 7727861
TI  - [Pleiotropic resistance associated with topoisomerases].
AB  - There are at least two well-characterized mechanism of resistance to Topo I and
      II inhibitors: modifications of intracellular accumulation and reduced formation
      of cleavable complexes. Limited drug accumulation is usually due to P
      glycoproteinMDR or to Multidrug Resistance associated Protein (MRP). Reduction of
      Topo I (or II) cleavable complexes not related to drug transport can either be
      due to decreased enzyme levels or enzyme mutations. For Topo II inhibitors,
      differential expression of the Topo II isoforms alpha and beta and changes in
      Topo II phosphorylation may also contribute to resistance. For dual Topo I and II
      inhibitors, resistance mechanisms are more complex to analyze but may also
      involve dual Topo I and II alterations. Finally, in a given cell line, several
      mechanisms are commonly associated in pleiotropic resistance to Topo inhibitors.

PMID- 7727862
TI  - [Resistance associated with the glutathione system].
AB  - Several mechanisms of resistance (of bacteria to antibiotics, of plants to
      herbicides, of insects to insecticides, of cancer cells to cytotoxic agents...)
      have now been described. The most studied one is the glycoprotein coded by the
      mdr1 gene, which is involved in the efflux of numerous compounds of natural
      origin (anthracyclines, podophyllotoxins...) thus decreasing the intracellular
      concentration of such drugs. Nevertheless, many chemotherapeutic protocols
      include alkylating agents, such as cyclophosphamide and cisplatin, which are
      electrophilic species prone to react readily with the tripeptide glutathione,
      most often through glutathione-S-transferases. Therefore, it appears of major
      importance to evaluate the role of glutathione and that of the polymorphism of
      the glutathione-S-transferases, as prognostic factors in the response to
      chemotherapy.

PMID- 7727863
TI  - The pharmacologic modulation of 5-fluorouracil with folinic acid, methotrexate,
      trimetrexate, and n-phosphonacetyl-l-aspartic acid (PALA). Mechanisms of the
      interactions and clinical data.

PMID- 7727864
TI  - [Pharmacokinetic mechanisms of resistance to anticancer medications].
AB  - Besides the cellular mechanisms of resistance, which can be described in terms of
      molecular alterations, the lack of sensitivity of a tumour to a drug may result
      from an inadequacy between the pharmacokinetics of the drug and the kinetics of
      the tumour cells. Dose and duration of infusion of a drug may govern its
      activity; the drugs exhibiting a short half-life in plasma and a marked phase
      dependence in their mechanism of action have to be administered as continuous
      infusions. The existence of sanctuary compartments within the body, which are
      protected by barriers such as the blood-brain barrier, may also contribute to the
      failure of the molecules unable to cross these barriers. Finally, the tumour cell
      kinetics may unfavour the general activity of drugs: this is the case of slowly
      growing tumours, which contain an important proportion of GO cells. The
      optimisation of the mode of administration of a drug is a requisite for the
      expression of its activity.

PMID- 7727865
TI  - [Drug resistance: from the laboratory to the clinic. Variations in drug
      resistance with time].

PMID- 7727866
TI  - [Methods for diagnosing MDR: immunohistochemistry versus molecular biology].
AB  - The methods of multidrug resistance (MDR) detection in human malignant tumors are
      numerous. The process of molecular biology (Slot Blot, Northern Blot, Reverse
      Transcription Polymerase Chain Reaction, PCR) and the process of in situ
      hybridization or immunohistochemistry are complementary. The process of molecular
      biology are quantitative and especially sensitive for PCR, by contrast they fail
      in specificity. This specificity is obtained by in situ hybridization and
      immunohistochemistry. However, none of these methods give knowledge of GP170
      functional activity. The detection of functional GP170 can be identified by
      rhodamine or daunorubicin intracellular accumulation with flux cytometry or by
      scintigraphically imaging GP170 expression in vivo with Tc-Sestamibi. The
      multiplicity of methods for detecting multidrug resistance show that there is no
      consensus about the best process to employ commonly. In consequence, the alone
      MDR biological diagnosis should not be the rationale of choice for second line
      chemotherapy or for using MDR revertant agents. In other words, the MDR
      biological diagnosis, keeping in mind that other chemoresistant mechanisms
      (topoisomerases, glutathione system, etc) could be present simultaneously or
      successively during tumor spreading or during successive antineoplastic
      treatments.

PMID- 7727867
TI  - [Drug sensitivity of bronchial small cell cancers transplanted to nude mice.
      Expression of the mdr1 gene and correlation with clinical practice. Effects of
      antagonists].

PMID- 7727868
TI  - [Trials of modulating the MDR1 phenotype in malignant hemopathies].
AB  - The first trials with modifier agents and chemotherapy were conducted in myeloma,
      with verapamil and VAD. The objective responses observed could not be
      undoubtfully rapported to the addition of modifier agent. The cyclosporin A could
      be given at 10 to 18 mg/kg/d by IV route during few days, without nephrotoxicity.
      A bone marrow toxicity was due to the modification of cytostatic
      pharmacokinetics. The remissions observed with addition of cyclosporin A or
      quinine in acute leukemia could be due to either the high dose of ara-C given
      with daunorubicin or mitoxantrone, or to the drug pharmacokinetic modifications,
      or the P-gp inhibition on leukemic cells (or probably a combination of these
      factors). Randomized trials are now going on.

PMID- 7727869
TI  - [Prevention of resistance to chemotherapy in the therapeutic strategy for
      cancer].

PMID- 7727870
TI  - [Use of immunodeficient mice in experimental cancer research].

PMID- 7727871
TI  - [Respective roles of the products of the mdr1 and p53 genes in drug resistance of
      bronchial cancers].
AB  - Expression of mdr1 and p53 was assessed on 119 cases of bronchial carcinomas, and
      compared with clinical chemoresistance. mdr1 expression was evaluated by
      immunohistochemistry (IHC), using the monoclonal antibody JSB1. The study of p53
      expression was performed by both IHC, using six different antibodies, and
      Northern blotting. We observed a correlation between the expression of mdr1 and
      the presence of a mutation of p53 in neuro endocrine (NE) carcinomas (P = 0.02).
      Correlation was not observed when non NE carcinomas were evaluated, nor was found
      any correlation between mdr1 expression and clinical chemoresistance in patients
      with small cell lung carcinoma (SCLC). The frequency of complete response however
      was significantly higher in patients whose tumor did no express mdr1 (P = 0.02).
      Chemoresistance correlated well with the phenotype of p53 mutant in SCC (P =
      0.015). We conclude that p53 mutation is a better predictive factor of clinical
      chemoresistance in SCLC than mdr1 IHC detection.

PMID- 7727872
TI  - Jaundice associated with Pseudomonas aeruginosa bacteremia complicating acute
      leukemia.
AB  - Two adult patients with acute leukemia developed marked jaundice during
      Pseudomonas aeruginosa bacteremia. The progressive increase in serum conjugated
      bilirubin levels was disproportionate to the gradual decrease in serum alkaline
      phosphatase and transaminase activity to or below low normal. The production of
      coagulation factors decreased. Autopsy revealed periportal cholestasis with
      minimal liver-cell damage. These findings suggested decreased metabolic activity
      of liver cells associated with bacteremia, probably leading to impaired bilirubin
      excretion. Both patients died despite appropriate antibiotic therapy. Isolated
      hyperbilirubinemia, thus, seemed to be an ominous prognostic sign in severe
      infection.

PMID- 7727873
TI  - Malignant hypercalcemia due to gastric endocrine cell carcinoma.
AB  - A 62-year-old man was admitted to our Neurology Unit due to consciousness
      disturbance. Laboratory data showed marked hypercalcemia and azotemia. Serum
      parathyroid hormone-related protein (PTHrP) level was extremely high. We
      performed intensive hemodialysis for renal failure, but his condition
      deteriorated rapidly. On day 10, he died of multiple organ failure. The autopsy
      revealed gastric undifferentiated adenocarcinoma with systemic dissemination.
      Immunohistological study showed positive PTHrP staining in carcinoid-like parts
      of the tumor. This is the first reported case of malignant hypercalcemia due to
      PTHrP-producing carcinoid or endocrine cell carcinoma of the stomach.

PMID- 7727874
TI  - Periodic angioedema with eosinophilia: increased serum level of interleukin 5.
AB  - A 48-year-old man developed episodic non pitting edema and eosinophilia. Symptoms
      were alleviated promptly when treated with prednisolone. However, major basic
      protein (MBP), eosinophil cationic protein (ECP), and eosinophil-derived
      neurotoxin (EDN) levels in the serum as well as the total number of eosinophils
      remained high. During periods of attack serum levels of interleukin-5 (IL-5) were
      elevated, but the levels were lowered following treatment, suggesting that IL-5
      is involved in periodic angioedema with eosinophilia.

PMID- 7727875
TI  - Crohn's disease associated with growth hormone secretory dysfunction.
AB  - A 10-year-old boy presented in 1989 with repeated episodes of vomiting, abdominal
      distension and severe growth retardation. Endocrinologic examination indicated
      growth hormone (GH) secretory dysfunction. Administration of recombinant human GH
      (rhGH) led to growth, but the patient discontinued treatment. He was readmitted
      to our hospital in 1993, at the age of 16. His stature was very short. Laboratory
      findings suggested malnutrition. Radiologic examination revealed regional
      stenosis and a cobblestone appearance of the intestine. The histologic diagnosis
      was compatible with Crohn's disease. Administration of prednisolone alleviated
      gastrointestinal symptoms with the improvement of GH secretory function.

PMID- 7727876
TI  - Smoldering adult T-cell leukemia with B-cell lymphoma and early gastric cancer.
AB  - We report a case of smoldering adult T-cell leukemia (ATL) with B-cell lymphoma
      and early gastric cancer. A 64-year-old man was admitted to our hospital because
      of proteinuria and hypergammaglobulinemia. Systemic lymphadenopathy, "flower
      cells" in peripheral white blood cells, and hypergammaglobulinemia with
      monoclonal gammopathy (IgA, lambda type) were found. As Southern blot analysis
      revealed monoclonal integration of human T-lymphotrophic virus type I proviral
      DNA in peripheral blood mononuclear cells, he was diagnosed as having smoldering
      ATL. The tissue specimen of an inguinal lymph node showed proliferation of
      abnormal lymphocytes which were stained with anti-lambda antibody, indicating B
      cell lymphoma. A polypoid lesion in the stomach was histologically diagnosed as
      early gastric cancer.

PMID- 7727877
TI  - Secondary amyloidosis associated with Castleman's disease.
AB  - A rare case of secondary amyloidosis associated with Castleman's disease is
      reported. A 53-year-old woman was referred for investigation of proteinuria.
      Biopsy specimens from kidney and gastric mucosa revealed numerous amyloid
      deposits, defined as AA amyloidosis by immunohistological staining. Castleman's
      disease was found in the abdomen as the primary disease for the amyloidosis.
      Although the urinary protein was somewhat reduced and the inflammatory findings
      were improved after removal of the lymphoma, renal insufficiency progressed and
      hemodialysis was begun.

PMID- 7727878
TI  - T-cell acute lymphoblastic leukemia with transient pure red cell aplasia
      associated with myasthenia gravis and invasive thymoma.
AB  - A 43-year-old male developed rapidly progressing anemia and a bone marrow
      examination revealed pure red cell aplasia (PRCA). He was diagnosed as having
      myasthenia gravis (MG) and invasive thymoma, and achieved complete remission by
      radiation and chemotherapy six years ago. Despite increased doses of oral
      prednisolone from 7.5 mg/day to 60 mg/day, a diagnosis of T-cell acute
      lymphoblastic leukemia (T-ALL) was made one month later based on findings of
      37.2% abnormal lymphoblasts and positive surface markers for CD2, CD3 and CD7 T
      cells. Cases of PRCA associated with MG and thymoma have been reported in the
      literature, however such a case followed by T-ALL is very rare.

PMID- 7727879
TI  - Herpes simplex encephalitis with transient global amnesia as an early sign.
AB  - Cerebral ischemia has been proposed as the etiology of transient global amnesia.
      Recently, however, migranous and epileptic etiologies have attracted attention. A
      56-year-old man had transient global amnesia and the next day began to display
      symptoms of meningoencephalitis. Herpes simplex encephalitis was diagnosed based
      on the titer of herpes simplex virus antibodies. The transient global amnesia
      appears to have occurred as an early sign of herpes simplex encephalitis and may
      have been provoked by an epileptic mechanism.

PMID- 7727880
TI  - Cholesterol emboli following percutaneous transluminal coronary angioplasty as
      speculated by toe skin biopsy.
AB  - A 55-year-old man required hemodialysis for acute renal failure 3 days after
      repeat percutaneous transluminal coronary angioplasty (PTCA). Bilateral
      acrocyanosis and necrotic lesions of the toes occurred 10 days after PTCA. Skin
      biopsy samples revealed needle-shaped cholesterol crystals of the intraluminal
      clefts in his small arteries. He was diagnosed with cholesterol emboli presenting
      as blue toe syndrome. The conditions improved with anticoagulation and
      vasodilation, but improvement in renal function was temporary. He later required
      maintenance hemodialysis. Cholesterol emboli following PTCA are life threatening
      because they are difficult to diagnose and can cause severe complications.

PMID- 7727881
TI  - Prognostic value of electroencephalogram (EEG) in anoxic encephalopathy after
      cardiopulmonary resuscitation: relationship among anoxic period, EEG grading and
      outcome.
AB  - We studied the prognostic applicability of electroencephalograms (EEGs) of
      seventy-nine patients within 24 hours after successful cardiopulmonary
      resuscitation. The EEGs were classified into five grades according to a modified
      Hockaday's scale. The EEGs of grades I and II implied full recovery, while those
      of grade III gave a varied but generally unfavorable prognosis. Patients with
      grades IV and V EEGs survived in a vegetative condition or died without
      awakening. Eighteen patients showed EEG with periodic patterns, all of which led
      to a fatal or vegetative outcome. One case showed EEGs associated with periodic
      triphasic waves and repetitive sharp transients in the same record. Several cases
      showed EEGs with different periodic patterns in consecutive records. We conclude
      that an EEG is a good indicator of patient prognosis after cardiopulmonary
      resuscitation. However, the clinical significance of morphological differences of
      various periodic patterns that can occur during an EEG remains to be established.

PMID- 7727882
TI  - Long-term follow-up of patients with a history of near fatal episodes; can
      inhaled corticosteroids reduce the risk of death from asthma?
AB  - We retrospectively studied the use of inhaled corticosteroids in patients who
      experienced near fatal episodes (NFE) to determine whether such therapy reduces
      the risk of death. Forty-eight patients who had near fatal episodes of asthma
      between January 1981 and December 1989 were divided into two groups. Group A
      comprised 19 patients who received beclomethasone dipropionate (BDP) daily (mean
      dose of BDP:687 micrograms/day: 200-2,000) following NFE, and Group B, 28
      patients who did not take BDP or who took less than 6 mg BDP/month. During the
      follow-up period (Group A:82.9 months, Group B:66.2 months), no patients in Group
      A died, but eight deaths occurred in Group B (mean period between near fatal
      episode and death was 31.5 months: 12-66). These results suggest that the regular
      use of inhaled corticosteroids, even at low doses, may reduce the risk of death
      in patients who experience NFE.

PMID- 7727883
TI  - Isozyme analysis of the high serum adenosine deaminase activity in patients with
      myasthenia gravis.
AB  - The serum activities of adenosine deaminase (ADA) and its isozymes (ADA 1 and ADA
      2) were measured in 31 patients with myasthenia gravis (MG). As compared with 50
      normal controls, in MG the total activity and ADA 1 were significantly high (p <
      0.01, respectively), and ADA 2 tended to be high. The total activity and ADA 2
      were higher in generalized MG than in ocular MG. ADA 2 was significantly higher
      in grade IIB patients as compared with grade I patients divided by Osserman's
      classification (p < 0.05). Patients with bulbar signs showed a significantly high
      total ADA (p < 0.05) with an increasing tendency for ADA 2. There was a
      significant elevation of the total activity and ADA 2 in patients with positive
      anti-acetylcholine-receptor antibody as compared to those of the negative
      antibody (p < 0.05). It was concluded that total ADA, reflecting the increase of
      both ADA 1 and ADA 2, is high in MG; and the measurement of ADA 2 is more
      important because ADA 2 was increased with advancing clinical MG grade.

PMID- 7727884
TI  - Percutaneous intracavitary antifungals for a patient with pulmonary aspergilloma;
      with a special reference to in vivo efficacies and in vitro susceptibility
      results.
AB  - A 61-year-old man with pulmonary aspergilloma received two antifungals
      intracavitarily. Although clinical, serological and roentgenographic improvement
      were observed with fluconazole therapy, bronchial secretions continuously yielded
      Aspergillus fumigatus. When fluconazole was switched to amphotericin B, the
      pathogen was eradicated immediately. The minimal inhibitory concentrations (MICs)
      of the isolate were 400 micrograms/ml for fluconazole, and 0.2 microgram/ml for
      amphotericin B. Although the discrepancy between in vitro and in vivo efficacy of
      antifungals has been argued, it was suggested the drug of choice should be
      selected on the basis of the MIC results at least in the intracavitary antifungal
      therapy for pulmonary aspergilloma.

PMID- 7727885
TI  - Adult-onset Still's disease with submassive hepatic necrosis.
AB  - We present a 74-year old woman who was hospitalized because of typical spiking
      fever, evanescent rash, polyarthralgia, lymphadenopathy, and marked elevation of
      serum transaminases and lactate dehydrogenase (LDH) due to adult-onset Still's
      disease (AOSD) with submassive hepatic necrosis. All of the symptoms and abnormal
      laboratory findings were dramatically improved after treatment with prednisolone.
      The clinical course of this patient indicates that AOSD with severe hepatic
      necrosis can successfully be treated with early administration of corticosteroid,
      although it remains unknown whether the disease can remain in remission with no
      or minimal treatment.

PMID- 7727886
TI  - Torsades de pointes associated with terfenadine in a case of liver cirrhosis and
      hepatocellular carcinoma.
AB  - A 65-year-old woman with liver cirrhosis complicated by hepatocellular carcinoma
      lost consciousness due to torsades de pointes with prolongation of the QT
      interval after 10 days of treatment with terfenadine. Before terfenadine
      administration, she had shown neither symptoms of heart disease nor any
      electrocardiographic abnormalities. Serum electrolytes were all normal, although
      the Ca level was near the lower limit of the normal range. After the withdrawal
      of terfenadine, the QT-interval was normalized and the torsades de pointes
      disappeared. Since she had liver cirrhosis, the development of torsades de
      pointes was thought to be attributable to the impairment of hepatic metabolism by
      terfenadine.

PMID- 7727887
TI  - Severe hyponatremia and hyperkalemia induced by trimethoprim-sulfamethoxazole in
      patients with Pneumocystis carinii pneumonia.
AB  - An antimicrobial agent trimethoprim-sulfamethoxazole (Tmp-Smx) does not usually
      cause electrolyte disturbances at regular doses, and few cases of Tmp-Smx-induced
      electrolyte imbalance have been reported in the English-language literature to
      date. Recently, however, we treated two patients with Pneumocystis carinii
      pneumonia who developed severe hyponatremia and hyperkalemia on administration of
      high-dose Tmp-Smx. These electrolyte disturbances were attributable to the direct
      effect of Tmp-Smx on the renal distal tubules, were reversible, and corrected by
      infusion of a sodium-enriched and potassium-free liquid. Therefore, it is
      suggested that even after electrolyte disturbances have occurred, high-dose Tmp
      Smx therapy may be continued for severe infectious diseases under appropriate
      electrolyte correction.

PMID- 7727888
TI  - Acinetobacter spp., saprophytic organisms of increasing pathogenic importance.
AB  - Acinetobacter spp. are Gram-negative non-fermentative bacteria commonly present
      in soil and water as free-living saprophytes; they are isolated as commensals
      from skin, throat and various secretions of healthy people. There have been
      frequent changes in their taxonomy so that their pathogenic role in humans has
      been understood only recently: Acinetobacter has emerged as an important
      nosocomial pathogen involved in outbreaks of hospital infections. This ubiquitous
      organism can be recovered from the hospital environment, from colonized or
      infected patients or from staff (hand carriage). Acinetobacter as an
      opportunistic pathogen is involved in nosocomial urinary tract infections,
      bacteremia, wound and burn infections. Its predominant role is observed in
      nosocomial pneumonia, particularly in fan-associated pneumonia. Acinetobacters
      are responsible for difficult-to-treat infections due to their frequent multiple
      resistance to major antibiotics available for the treatment of nosocomial
      infections. Various mechanisms of resistance to beta-lactams and aminoglycosides
      have been recognized in these bacteria. Combination therapy is usually
      recommended for the treatment of nosocomial infections. The increasing pathogenic
      importance of Acinetobacter spp. and the increasing frequency of hospital
      outbreaks of acinetobacter infections has made the development of reliable typing
      methods imperative. Beside conventional "phenotypic" methods (serology, phage
      typing), genotypic systems (ribotyping, plasmid profiles, pulse-field gel
      electrophoresis) are currently advancing.

PMID- 7727889
TI  - Characterization of the specific antigenicity of representatives of M.
      senegalense and related bacteria.
AB  - Representative strains of M. senegalense and an unusual strain, labelled M.
      farcinogenes (M280) were examined by thin-layer chromatography for the presence
      of characteristic surface glycolipids. In the case of M. farcinogenes M280 and M.
      senegalense M264, the glycolipids were of the alkali-labile acyltrehalose
      lipooligosaccharide (LOS) class of antigens, whereas M. senegalense M263 was
      found to contain the alkali-stable glycopeptidolipids (GPL). Through a
      combination of 1H-NMR, methylation analysis, FAB/MS, and other analytical
      techniques, the structures of these glycolipids were deduced. The LOS glycolipids
      were found to be similar in structure to the characteristic glucosyltrehalose
      based glycolipids isolated previously from clinical isolates of M. fortuitum, but
      distinct from the diacyltrehaloses characteristic of the type strain of M
      fortuitum. The glycopeptidolipids from M. senegalense M263 were closely similar
      to those characterized previously from M.

PMID- 7727890
TI  - Use of ribotyping, IS200 typing and plasmid analysis for the identification of
      Salmonella enterica subsp. enterica serovar Typhimurium vaccine strain Zoosaloral
      H and its differentiation from wild type strains of the same serovar.
AB  - Fifty Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium)
      isolates obtained from one vaccinated and three non-vaccinated poultry flocks as
      well as the commercially available vaccine strain Zoosaloral H and a S.
      Typhimurium reference strain were characterized genotypically to differentiate
      between S. Typhimurium live vaccine strain Zoosaloral H and wild type strains of
      the same serovar. Ribotyping revealed five different patterns one of which
      exclusively occurred in the vaccine strain. Seven different hybridization
      patterns could be observed by IS200-typing of the S. Typhimurium isolates; one of
      them was only detectable in the vaccine strain. Plasmid analysis showed that 51%
      of the S. Typhimurium isolates including the vaccine strain harboured large
      plasmids of approximately 60 MDa. Hybridization with a virulence gene probe
      identified only 48% of these large plasmids, including that of the vaccine
      strain, to carry this virulence-associated gene. However, restriction
      endonuclease analysis of the hybridizing plasmids showed that the virulence gene
      was located on HindIII fragments of different sizes in the plasmid of the S.
      Typhimurium vaccine strain Zoosaloral H and in the plasmids of the respective
      wild type S. Typhimurium isolates. Thus, ribotyping, IS200-typing and plasmid
      analysis represent at least three independent systems which allow the genotypic
      identification of the S. Typhimurium vaccine strain Zoosaloral H and its
      differentiation from wild type isolates of the same serovar.

PMID- 7727891
TI  - Detection of pneumococcal polysaccharide antigens in the urine of patients with
      bacteraemic and non-bacteraemic pneumococcal pneumonia.
AB  - Countercurrent-immunoelectrophoresis (CIE) was used to detect pneumococcal
      capsular polysaccharide and C-polysaccharide (C-Ps) antigens in urine. The
      neutral capsular polysaccharides of types 7F and 14 were detected by
      coagglutination. We found pneumococcal polysaccharide in urine with the same
      frequency in two groups of patients, i.e. a non-bacteraemic pneumonia group (68%)
      and a group of patients with pneumococcal bacteraemia (66%). C-Ps was detected in
      the urine of two patients (4%) and, therefore, this test has no value in the
      diagnosis of pneumococcal infections. Since there is no sensitive, non-invasive,
      single procedure for the diagnosis of non-bacteraemic pneumococcal pneumonia we
      conclude that attempts to detect pneumococcal capsular polysaccharide by CIE in
      combination with coagglutination (types 7F and 14) may be a useful diagnostic
      supplement in the search for the etiological agent in pneumonia in adults until
      new, more sensitive diagnostic methods have been developed.

PMID- 7727892
TI  - Clamped homogenous electric fields (CHEF) gel-electrophoresis of DNA restriction
      fragments for comparing genomic variations among strains of yersinia
      enterocolitica and Yersinia spp.
AB  - Yersinia enterocolitica gastroenteritis was first recognized in the early 1960s
      and has since been reported with increasing frequency. To determine if strains of
      Y. enterocolitica, within a restricted region isolated over 8 years (1985-1993),
      originated from a single or multiple clones, pulsed-field gel electrophoresis
      (PFGE) of large chromosomal DNA restriction fragments generated by XbaI or NotI
      was used. A total of 27 isolates of Y. enterocolitica were analyzed, 24 from
      Austria (Vienna and Graz) consisting of serogroups 0:3 (17 isolates), 0:9 (6
      isolates), 0:5 (1 isolate); 2 from Germany of serogroups 0:3 and 0:9 (1 isolate
      each); 1 from the U.S.A. of serogroup 0:8. Genomic fingerprints of these strains
      were compared to those of 8 other Yersinia species to ascertain if their
      restriction endonuclease digestion profiles (REDP) were serogroup and/or species
      specific. The 27 Y. enterocolitica strains could be divided into 16 genomic
      varieties according to their restriction patterns with NotI and XbaI. PFGE was
      highly discriminatory as strains belonging to the same serogroup could be
      subdivided into different genomic groups. Furthermore, Y. enterocolitica strains
      isolated from the same region, over an 8 year period, belonged to a few closely
      related clones. The genomic fingerprints of Yersinia were found to be species and
      serogroup specific.

PMID- 7727893
TI  - Increase of ciprofloxacin resistance in Campylobacter species in Styria, Austria.
AB  - Salmonella spp. and thermophilic Campylobacter spp. are the most important
      diarrhea-causing pathogens in the area investigated in Styria, Austria. The
      isolation rate of Campylobacter in the more than 62,000 stool specimens
      investigated in the six-year period between 1988 and 1993 ranged between 1.90% in
      1988 and 3.58% in 1991. The testing of susceptibility to nalidixic acid has been
      an usual characteristic for species identification. Nalidixic acid-resistant
      strains were rare in 1988-1990, but in the summer of 1991, we found an increasing
      number of these isolates. At the same time, we learnt about the increasing use of
      enrofloxacin in veterinary medicine, especially in the poultry industry, and
      therefore we started routine testing of Campylobacter spp. susceptibility to
      ciprofloxacin in 1992. In 1992, the resistance rate to ciprofloxacin was already
      16.9%, rising to 22.1% in 1993.

PMID- 7727894
TI  - Antigenicity and antigenic cross-reactivity of outer membrane proteins of Vibrio
      parahaemolyticus.
AB  - Antigenicity of outer membrane proteins was studied and compared between Kanagawa
      positive (clinical) and negative (environmental) strains of Vibrio
      parahaemolyticus. Murine antibodies recognized a wide range of outer membrane
      proteins of Kanagawa negative strains as antigens with molecular masses ranging
      between 102 kDa to 14 kDa. However, only a few of the total outer membrane
      proteins of clinical isolates were antigenic and comprised a 55kDa protein as the
      major antigen. Although a marked difference in antigenicity was found, molecular
      masses of outer membrane proteins of Kanagawa positive and negative strains
      migrated similarly in SDS-PAGE. Several outer membrane proteins of Kanagawa
      positive strains were found to be antigenic and ubiquitous in a cross-reactivity
      study indicating that the ubiquitous proteins which could not be recognized by
      anti-KP antibodies were buried in the outer membrane.

PMID- 7727895
TI  - Serum antibody responses to vaccination with 23-valent pneumococcal vaccine in
      splenectomized patients.
AB  - Sixty-three patients that have been splenectomized for various disorders were
      vaccinated with Pneumovax 23, the currently available pneumococcal vaccine.
      Before and one month after splenectomy, IgG antibodies against 8 pneumococcal
      polysaccharide antigens (types 3, 4, 6B, 7F, 10A, 14, 19F, and 20) were
      determined by a highly reproducible and type-specific enzyme-linked immunosorbent
      assay (ELISA). In order to increase the specificity of the assay, this method
      involved the use of a capture antibody (F(ab')2-fragments of a type-specific
      rabbit antipneumococcal hyperimmune serum) to bind the pneumococcal antigens to
      the plastic surface of microtiter plates and the absorption of these sera with
      the cross-reacting C polysaccharide. Rates of patients showing a two-fold
      antibody increase were dependent on pneumococcal type, ranging from 12.7% to
      33.3%. Antibody responses of single patients were not uniform for all
      pneumococcal serotypes investigated. Only one patient responded to all of the
      eight antigens tested. In spite of relatively low response rates, splenectomized
      patients should be routinely vaccinated with the pneumococcal vaccine, especially
      when the low rate of adverse reactions is taken into consideration. It is
      emphasised that the results of the present study and those reported in the
      literature have to be compared and interpreted with caution, because the
      available data on the antibody response to pneumococcal vaccination are based on
      assays that differ substantially in methodology.

PMID- 7727896
TI  - Combined immunomodulation (Propionibacterium avidum KP-40) and lectin blocking (D
      galactose) prevents liver tumor colonization in BALB/c-mice.
AB  - The protective effect of combined treatment (immunomodulation with
      Propionibacterium avidum KP-40; liver lectin blocking by D-galactose
      administration) on the liver colonization of RAW 117-H10 lymphosarcoma was
      investigated in BALB/c-mice. Both, immunomodulation with P. avidum KP-40 as well
      as liver lectin blocking by D-galactose treatment significantly decreased the
      number of liver tumor colonies in this experimental model. However, the
      combination of P. avidum KP-40 and D-galactose obviously proved to be superior to
      each monotherapy since the liver colonization by RAW 117-H 10 lymphosarcoma could
      be completely inhibited.

PMID- 7727897
TI  - Role of antibodies against fibronectin-, collagen-binding proteins and alphatoxin
      in experimental Staphylococcus aureus peritonitis and septicaemia in neutropenic
      mice.
AB  - We have investigated the protective role of hyperimmune rabbit IgG against two
      surface structures of Staphylococcus aureus, i.e. fibronectin-, and collagen
      binding proteins as well as alpha-toxin in experimental peritonitis and
      septicaemia in neutropenic mice pretreated with cyclophosphamide. This treatment
      markedly decreased clearance of bacteria from mouse organs. With combined
      immunotherapy given passively bacteria were eradicated more efficiently for all
      animals sampled, comparative to controls.

PMID- 7727898
TI  - Typing and strain differentiation of clinical herpes simplex virus type 1 and 2
      isolates by polymerase chain reaction and subsequent restriction fragment length
      polymorphism analysis.
AB  - In the present study, different combinations of primers were investigated for PCR
      amplification and typing of clinical herpes simplex virus type 1 (HSV-1) (n = 22)
      and herpes simplex virus type 2 (HSV-2) (n = 12) isolates. Intratypic strain
      differentiation was performed by restriction fragment length polymorphism (RFLP)
      analysis of different PCR amplified HSV genome regions. Enzymatic amplification
      of HSV DNA from all the clinical isolates could be achieved using primer
      combinations DNAP5/DNAp3-1 (HSV-1), DNAP5/DNAP3-2 (HSV-2). With the primer pair
      corresponding to the thymidine kinase (TK) genome region, amplification of all
      the HSV-1 isolates was only possible by nested PCR. With primers HSV UP/DOWN, 10
      of 12 HSV-2 isolates could be detected. HSV typing by type-specific primers
      DNAP5/DNAP3-1 (HSV-1), DNAP5/DNAP3-2 (HSV-2) or restriction enzyme analysis (Ava
      II) of amplified DNA with HSV-specific UP/DOWN primers showed results which
      concorded with serotyping by monoclonal antibodies. RFLP analysis of the PCR
      products using selected restriction enzymes showed sufficient diversity of
      profiles among strains to differentiate all the HSV-1 isolates and to distinguish
      four groups of HSV-2 isolates. Amplification of HSV DNA from clinical isolates
      with subsequent typing and strain differentiation represents a valuable
      alternative to conventional methods (virus isolation, serotyping and restriction
      fragment analysis of the entire genomic DNA) and may be suitable for the study of
      HSV transmission and pathogenesis, especially in labour-intensive clinical
      samples with low levels of virus replication (i.e. cerebrospinal fluid, vitreous
      fluid and corneal transplants).

PMID- 7727899
TI  - Comparison of high-performance liquid chromatography and bioassay for the
      determination of 5-fluorocytosine in serum.
AB  - An HPLC method using a reverse phase system, an isocratic mobile phase and simple
      protein precipitation and a plate diffusion bioassay using an amphotericin B
      resistant strain of Candida pseudotropicalis for the measurement of 5
      fluorocytosine in serum were compared. Both methods permit a determination of 5
      fluorocytosine in sera also in the presence of amphothericin B. The correlation
      between bioassay and HPLC runs was found to be r = 0.96. Both methods are useful
      for monitoring the serum level of 5-fluorocytosine in clinical routine.

PMID- 7727900
TI  - Detection of a circulating parasitic antigen in acute infections with Trichinella
      spiralis: diagnostic significance of findings.
AB  - Circulating parasitic antigen was demonstrated in the sera of rats and patients
      infected with Trichinella spiralis. Using a dot-immunobinding method, the antigen
      was detected in the sera of experimental animals from the fourth day of infection
      and in more than one third of the patients by the end of the third week from
      infection. The method proved to be simple, sensitive and specific. It should
      assist an early diagnosis of trichinellosis demonstrating the antigen in some
      cases with negative or doubtful results for specific antibodies.

PMID- 7727901
TI  - Distribution of genes conferring combined resistance to tetracycline and
      minocycline among group B streptococcal isolates from humans and various animals.
AB  - Forty-nine tetracycline and minocycline resistant streptococci of serological
      group B isolated from humans, cattle, pigs and nutrias were investigated for the
      presence of genes conferring this combined resistance. Southern blot
      hybridization of EcoRI-digested chromosomal DNA of the bacteria revealed for 39
      of the cultures a hybridization signal with tet(M), for four of the cultures a
      hybridization signal with tet(O) and for none of the cultures a hybridization
      signal with the tet(Q) gene probe. The restriction endonuclease digested and
      blotted DNA of six tetracycline and minocycline resistant group B streptococci
      did not hybridize with any of the available gene probes. The tet(M) gene probes
      recognized complementary sequences of EcoRI fragments of approximately 10.5 kb
      and 21.5 kb, the tet(O) gene probe hybridized with fragments of approximately 19
      kb. The hybridization of the tet(M) gene probe in two different patterns appeared
      to be related to the origin of the cultures.

PMID- 7727902
TI  - An outbreak due to enterohaemorrhagic Escherichia coli O157:H7 in a children day
      care centre characterized by person-to-person transmission and environmental
      contamination.
AB  - An outbreak of gastrointestinal disease and haemolytic uraemic syndrome caused by
      Escherichia coli O157:H7 was investigated. The outbreak occurred in a day care
      centre located in northern Germany in August 1992 and involved 39 children and
      two adults. Furthermore, four asymptomatic infections were detected among the
      staff. Initial and secondary cases were reported over a 30-day interval, with
      cases occurring in three waves. Person-to-person contact and environmental
      contamination were assumed to be the main mode of transmission. The source of the
      outbreak has remained unknown but it is likely that primary or secondary
      contamination of the day care centre's kitchen, too, played a role in the spread
      of infections. The organisms were isolated from two open packs of deep-frozen
      stuffed cabbage rolls and turkey scallops in batter, and furthermore from swabs
      from two kitchen utensils. Of the 39 cases with diarrhoea, three developed a
      haemolytic uraemic syndrome; one of the latter patients died. In 8 of the cases
      as well as in four healthy adult employees, E. coli O157:H7 was isolated from
      stool samples, and in two stool culture-negative cases the presence of IgM
      antibody to O157 LPS indicated recent infection. The E. coli O157:H7 isolates
      from the cases and the kitchen were of identical phage type and yielded identical
      biochemical reactions. All E. coli O157:H7 isolates harboured stable slt-II
      genes. However, slt-I genes could only be demonstrated in the primary cultures
      and were lost during subcultivation. This is the largest outbreak caused by
      enterohaemorrhagic E. coli O157:H7 that has been documented in Germany so far.
      The high infectivity of the organism which was demonstrated by person-to-person
      transmission and propagation within certain groups of children stresses the need
      for strict hygienic measures and early case reporting when such infections occur
      in susceptible settings like day care centres, nursing homes, or hospitals.

PMID- 7727903
TI  - Campylobacter jejuni infection and the Guillain-Barre syndrome: mechanisms and
      implications.

PMID- 7727904
TI  - The influence of Propionibacterium acnes (Corynebacterium parvum) fractions on
      immune response in vivo.
AB  - Bacterin of Propionibacterium acnes (Corynebacterium parvum), its cellular
      fractions (lipids, fractions obtained by mechanical disruption and differential
      centrifugation, by phenol-water and pyridine extractions), and a polysaccharide
      from culture filtrate were prepared and tested in mice. The activation of RES by
      splenomegaly and hepatomegaly, prevention of listerial infection, prevention of
      the lethal effect of sarcoma 180, and depression of liver microsomal cytochrome P
      450 were employed. The bacterin was effective in all tests. Lipid-free cells were
      less active, in particular in the activation of RES and in the listerial
      infection model. Fractions prepared by the disruption and differential
      centrifugation lost their activity in all tests along with a decrease in
      molecular weight. Lipids extracted by ethanol caused pronounced splenomegaly and
      decreased the cytochrome P-450 content. The residue left after the phenol-water
      extraction was very active, its delipidation did not destroy the activity.
      Pyridine extraction provided a completely inactive extract, but a very active
      residue. The possibility of reducing the complexity of bacterin while preserving
      immunomodulatory effect is demonstrated.

PMID- 7727905
TI  - Collaboration: a critical viewpoint.
AB  - Post-graduate nursing education in Victoria, until recently, has been conducted
      as certificate level courses within hospital-based programs. These programs have
      traditionally drawn on the clinical experience, the supervision and the teaching
      provided by the resources within the hospital. This article describes the nature
      of a collaborative venture, involving regional hospitals and the university, and
      the challenges that emerged during the introduction of a post-graduate critical
      care course. Issues arising out of the course evaluation, which was conducted
      after the first year of the program elaborate aspects of the beginning nature of
      a collaborative venture. These issues include the different emphases and
      expectations of skills and knowledge, perceived as relevant to critical care
      practice. Some of the difficulties encountered by the students are raised. We
      employ the concepts of liberal and vocational/professional education to explore
      the ways in which present tensions signify what we have discovered to be an old
      pedagogical debate. The particular meanings we have as a profession when we speak
      about education are explored in the context of critical care education and
      collaborative practice.

PMID- 7727906
TI  - The use of position during critical illness: current practice and review of the
      literature.
AB  - This descriptive study looked at how nurses positioned the critically ill person
      in the Intensive Care Unit. Its objective was to identify what positions were
      utilised, and whether severity of illness influenced this choice. The findings
      show nurses are conservative in their use of position during critical illness.
      There was only limited use of elevation of the backrest of the bed or rotation to
      the side during the side lying position. As the severity of illness increased,
      more horizontal positions were utilised. These findings and review of the
      literature highlights a need for further research into specific aspects of the
      use of position during critical illness.

PMID- 7727907
TI  - 'Of rocks and hard places'.

PMID- 7727908
TI  - Failure of intravenous low dose midazolam to influence memory recall in drug
      paralysed post-operative patients sedated with papaveretum.
AB  - Sedation of ventilated patients in the Intensive Care Unit generates a tension
      between adequate sedation to maintain comfort and ease of ventilation and over
      sedation with undesirable prolongation of ventilation and delays in discharge.
      Studies in animals suggest very low dose midazolam, but not higher doses,
      potentiate the sedative effects of opiates. We undertook a trial of opiate
      sedation versus opiate sedation plus low dose midazolam (1 mg/hour) to determine
      whether a similar effect could be demonstrated in man. Although ventilator time
      and the duration of admission to Intensive Care was not prolonged by the addition
      of midazolam, we were unable to demonstrate any statistically significant benefit
      with regard to memory recall.

PMID- 7727909
TI  - Funding intensive care in the DRG age: an overview.

PMID- 7727910
TI  - Assessment and management of the client experiencing myocardial ischaemia.
AB  - The management of myocardial ischemia requires prompt assessment and
      intervention. Nursing assessment should be systematic, with every possible clue
      being integrated to help form a diagnostic picture. Assessment includes not only
      pain assessment but also assessment of psychological status and physiological
      response. An understanding is required of normal coronary flow and myocardial
      perfusion in order to then intervene in a therapeutic manner. Management should
      be focused on pain relief, diminution of anxiety and strategies to redress
      myocardial oxygen demand/supply imbalance. This article discusses a systematic
      framework to facilitate prompt and effective assessment and management of a
      client experiencing myocardial ischaemia. It builds on the description of the
      neurological pathways of cardiac pain provided in Part 1, Beetson, R. Pain in the
      client experiencing myocardial ischaemia-Nursing assessment and management. Part
      1-Neurophysiology and clinical manifestations of myocardial ischaemia pain.

PMID- 7727912
TI  - Chest x-rays. Tubes, catheters and wires.

PMID- 7727911
TI  - The basic knowledge assessment tool: is it useful?
AB  - Registered Nurses (RN's) caring for the critically ill, require a wide range of
      specialised skills and knowledge. Assessing knowledge of RN's within Intensive
      Care Units (ICU's) is imperative if we are to ensure that patients are afforded
      quality care. The aim of this study was to evaluate existing knowledge of the
      RN's working in the ICU of a major teaching hospital using the Basic Knowledge
      Assessment Tool (BKAT). Overall mean test scores of 78% were encouraging.
      Knowledge gaps were evident in gastrointestinal and endocrine disorders.
      Significantly higher scores were obtained by RN's trained in the hospital based
      system (p = 0.02) and those possessing ICU qualifications (p = 0.01). There were
      no differences in scores according to age and length of ICU experience.
      Registered nurses scored badly in a number of questions, which highlighted some
      problems in the terminology used in the BKAT.

PMID- 7727913
TI  - World congress on critical care nursing.

PMID- 7727914
TI  - The guidelines for judging abstracts and free papers.

PMID- 7727915
TI  - "The InANE connection".

PMID- 7727916
TI  - New standards for emergency admissions.

PMID- 7727917
TI  - The future for nurses in purchasing.

PMID- 7727918
TI  - Stoma care: finding the most appropriate appliance.
AB  - Over the last 25 years a wide range of stoma appliances have become available via
      the Drug Tarriff because of the post-war development of plastics. Before deciding
      which is the most appropriate appliance for the stoma patient to use, it is
      important to carry out an holistic assessment and understand which type of stoma
      bag is correct for the appropriate stoma.

PMID- 7727919
TI  - Hazards of sharps disposal.
AB  - The disposal of sharps continues to be one of the most hazardous procedures for
      clinical staff. This article looks at the dangers encountered and the precautions
      necessary to ensure the safe disposal of sharps.

PMID- 7727920
TI  - Death of a patient. 1: A personal reflection.
AB  - Reflection on practice has been identified as a means of bridging the theory
      practice gap, encouraging a questioning, self-evaluative approach to nursing
      practice. In this two-part article, a clinical incident regarding the management
      of bereaved relatives is explored, utilising a model of structured reflection.

PMID- 7727921
TI  - Use of physical restraints. 2: Alternatives.
AB  - The first article in this two-part series considered the consequences of physical
      restraints. This article considers the alternatives to physical restraints and
      argues that their use in daily nursing practice raises the quality of care
      provided to elderly patients.

PMID- 7727922
TI  - Building a future for mental health nursing.

PMID- 7727923
TI  - The aftermath of suicide.
AB  - This article discusses the aftermath of a suicide. It describes the patient who
      died and discusses the review that followed the suicide. Many of the issues
      raised are relevant to both community-based and hospital-based care.

PMID- 7727924
TI  - Suicide and psychological debriefing.
AB  - The death of a patient by suicide is one of many upsetting experiences that
      nurses face. However, psychological debriefing after such an event is not
      commonly available.

PMID- 7727925
TI  - Supervising suicidal patients within a hospital setting.
AB  - Recent reports have highlighted areas of inadequacy within mental health services
      which can lead to suicide. This article examines the support mental health nurses
      should be given to improve their clinical practice in an effort to reduce the
      risk of suicide.

PMID- 7727926
TI  - Suicide: the crisis in the prison service.
AB  - Suicide presents major management difficulties in the prison service. This
      article examines factors that contribute towards suicide in prisons and discusses
      recommendations for tackling the problem more effectively.

PMID- 7727927
TI  - The nature of scientific knowledge: fact or theory?
AB  - The complex and confusing literature on nursing theories and theory building is
      considered in this article. The distinction between facts and theories is
      explained.

PMID- 7727928
TI  - Nurses needs a more flexible grading and pay structure.

PMID- 7727929
TI  - Implementing professional profiling.
AB  - This year, UKCC requirements for maintaining an effective registration will
      necessitate practitioners keeping professional development details in a personal
      professional profile. This article describes the former Yorkshire Regional
      approach in preparing for this event and the workshop experiences.

PMID- 7727930
TI  - Law series: 4. Consent to treatment.

PMID- 7727931
TI  - Nurses deserve fair pay for fair play.

PMID- 7727932
TI  - Haematology blood testing for anaemia.

PMID- 7727933
TI  - Assessment of urinary incontinence in neuroscience patients.

PMID- 7727934
TI  - Death of a patient. 2: A personal reflection.

PMID- 7727935
TI  - The support of the family within the acute clinical area.

PMID- 7727936
TI  - Defining specialist nursing.

PMID- 7727937
TI  - Education for specialist and advanced practice.

PMID- 7727938
TI  - The scope of advanced practice: action potential for practice nurses.

PMID- 7727939
TI  - Advocacy: a specialist practitioner role.

PMID- 7727940
TI  - Induction: moving from the specific to the general.

PMID- 7727941
TI  - Iodosorb and Iodoflex.

PMID- 7727942
TI  - Common problems in wound care: wound cleansing.

PMID- 7727943
TI  - Specialisation in nursing comes of age.

PMID- 7727944
TI  - Should resource allocation influence treatment decisions?

PMID- 7727946
TI  - Continence: a challenge for us all.

PMID- 7727945
TI  - The impact of reducing junior doctors' hours on nursing.

PMID- 7727947
TI  - IMMEL: assessing coping responses in the early stages of dementia.
AB  - A sufferer's perspective on ways of coping with the initial and evolving impact
      of dementia is a largely unexplored area of theory and practice. This article,
      the first of two parts, outlines the development of a new instrument: the Index
      for Managing Memory Loss (IMMEL), which considers the early sufferer's response
      to the experience of dementia and can be used to assist practitioners assess
      individuals' coping strategies. Some additional avenues for professional
      intervention are also suggested.

PMID- 7727948
TI  - Use of transcendental meditation to relieve stress and promote health.
AB  - The relief of stress is an important part of health promotion. This article
      examines the effects of transcendental meditation on stress and discusses how it
      can improve health.

PMID- 7727949
TI  - A holistic approach to pressure sore management.
AB  - Caring for a pressure sore requires a holistic approach. Incontinence complicates
      the management of wounds. Encouraging patient participation in pressure sore
      management promotes ownership of the sore. Consistency in documentation allows a
      consistent and objective evaluation of healing. Recognition of any deficits in
      knowledge, and education to meet these, enhances patient safety.

PMID- 7727950
TI  - Stress incontinence: treatment using pelvic floor re-education.
AB  - Stress incontinence is the most common cause of urinary incontinence. A pelvic
      floor assessment is an essential prerequisite to all pelvic floor exercise
      programmes. Many patients with stress incontinence can be cured using a programme
      of exercises. The use of weighed pelvic floor cones with an exercise programme
      increases compliance and enables patients to perform resisted exercises in their
      own homes.

PMID- 7727951
TI  - An investigation of the uncurling forces of indwelling catheters.
AB  - An elastic catheter in the male urethra produces an 'uncurling' force as it
      attempts to straighten itself. Where this force is sustained, it may result in
      some pressure necrosis, or pressure atrophy. This article describes how this in
      vivo situation was modelled and the resultant pressures checked and recommends
      the type and size of catheter that should be used if it is needed for more than 2
      days of continuous use.

PMID- 7727952
TI  - In control with incontinence aids.
AB  - Incontinence is a common condition affecting people of all ages. Many can be
      cured and all can benefit from appropriate treatment and management. Despite huge
      growth in this market, many products are neither appealing nor acceptable to
      those people who have to use them. Whenever practical, it is best that the choice
      of aid should be a collaborative decision between the user and the carer.

PMID- 7727953
TI  - Deduction: moving from the general to the specific.
AB  - This article considers the issue of theory testing, using the hypothetico
      deductive model. The nature and purpose of hypotheses are explored and the
      varying types of hypotheses are described.

PMID- 7727954
TI  - Managed care. 2: An opportunity for nursing.
AB  - The first part of this article described some of the tools of a managed care
      system. This article suggests ways in which the nursing role can be developed to
      take forward the opportunities offered by managed care.

PMID- 7727955
TI  - Nimbus and Alpha X Cell.

PMID- 7727956
TI  - Nurses' role in the decision-making process.

PMID- 7727957
TI  - Law series: 5. Confidentiality.

PMID- 7727958
TI  - [Satisfaction of paid thrombocyte donors with instrumental thrombocytapheresis].
AB  - OBJECTIVE: The increasing need for single-donor platelet concentrates makes it
      necessary to motivate platelet donors to donate regularly. The authors examined
      the contentment of existing donors in order to create a basis for improvements
      and to raise the attractiveness of donation. DESIGN: Open empirical data
      acquisition. SETTING: Institute for Transfusion Medicine at the General Hospital
      Vienna. PARTICIPANTS: 211 platelet donors. INTERVENTIONS: Interview with a self
      developed questionnaire. RESULTS: Whereas donors rate the work of the staff as
      being very good, they are less content with the surroundings in the pheresis
      unit. Younger and higher-educated donors as well as persons who have been
      donating for less than 5 years show more negative ratings than comparable groups.
      The financial compensation is important to ensure a high donation frequency.
      CONCLUSIONS: The attractiveness of donation could be raised by improving certain
      aspects of donation. In order to ensure a high donation frequency donors should
      be granted a financial compensation, as otherwise particularly younger donors,
      who are more likely to be seronegative for antibodies to CMV, would not donate
      any more or at least not that often.

PMID- 7727959
TI  - [Survey of blood donors on the topic of "reimbursement for blood donors"].
AB  - BACKGROUND: Remuneration for blood donors, in the way as presently handled by
      governmental and communal blood transfusion services in Germany, is not generally
      accepted. It is feared that donors are recruited with increased risk to transmit
      infectious diseases, especially AIDS. Alternative incentives are discussed. After
      the so-called AIDS scandal in Germany, a change in the donor motivation was to be
      expected, associated with an increased willingness to renounce remuneration.
      Therefore, we performed the present survey, in which we evaluated the donor's
      willingness to renounce remuneration, possibilities of cashless remuneration and
      other alternative incentives. MATERIAL AND METHODS: During March and April 1994,
      a total of 1,157 blood donors of the University Blood Bank Marburg were
      questioned anonymously by a questionnaire in the framework of whole-blood
      donations. Beside the above-mentioned aspects demoscopic data were included (age,
      sex, profession, journey). RESULTS: Cutting of remuneration without any other
      compensation was refused by 86.1% of the donors, 77% would not want to further
      donate blood in this case. Transfer of money to a bank account instead of cash
      payment was accepted by 78.6%, the use of non-negotiable cheques by 68.7%.
      Alternative compensation by tickets for theater, concert, cinema or coupons for
      restaurants met with the approval of only 27.3%; under these circumstances, 36.9%
      would be willing to continue blood donation. With increasing age and number of
      donations, but largely independent of social status, donors attached greater
      importance to retention of remuneration. DISCUSSION: Cutting of remuneration
      would result in a considerable reduction of the willingness to donate blood
      within the population of donors of the governmental and communal blood
      transfusion services. However, an increase of virus safety of the blood products
      would not be reached in this way, since especially the long-term donors would be
      driven away. Considerable bottlenecks, particularly in the specific blood supply
      of hospital-integrated blood transfusion services, would have to be expected.

PMID- 7727960
TI  - [Observations on antibody determination and differentiation with papain test
      erythrocytes using the gel centrifugation technique (ID-Microtyping System)].
AB  - BACKGROUND: The gel centrifugation system (ID Microtyping System, Fa. Diamed,
      Bensheim, FRG) is one of several new methods, which has become commercially
      available within the last few years for the detection of antibodies against red
      blood cell antigens. MATERIALS AND METHODS: During 1 year we used the gel
      centrifugation method for antibody screening in our routine laboratory by
      performing 3 tests each time: 1. NaCl card (room temperature) with untreated red
      cells; 2. NaCl card (37 degrees C) with papain-treated red cells, and 3. Liss
      Coombs card (37 degrees C) with untreated red cells. RESULTS: The two-stage
      papain test revealed some interesting phenomena: 1. In some cases the sensitivity
      of the papain gel test is higher than that of all other methods tested in this
      study, namely in the gel centrifugation technique and in the tube centrifugation
      technique. 2. There are reactions which seem to be directed against patients' own
      antigens (in the Rhesus or Kidd system), but there are no positive direct
      antiglobulin test and no clinical signs of hemolysis. 3. Some sera show reaction
      patterns which seem to have a distinct specificity, but they cannot be assigned
      to any of the antigens in the manufacturer's antigenogram. CONCLUSIONS: Before a
      general recommendation for antibody screening with the two-stage papain test in
      the gel centrifugation method can be given, further investigations about the
      clinical value of those antibodies which are detectable only by this technique
      are necessary. For antibody identification further declarations in the work sheet
      of the panel would be desirable.

PMID- 7727961
TI  - [Detection and side effects of isoantibodies in intravenously administered
      immunoglobulin preparations].
AB  - BACKGROUND: Intravenous immunoglobulins (IvIg) contain not only the declared
      antibodies against pathogenic microorganisms, but also all the other antibodies
      of the blood donors, e.g. against erythrocytic antigens. MATERIALS AND METHODS:
      We tested 14 IvIg from 7 manufacturers (a total of 40 charges) for isoantibodies
      and irregular antibodies. To improve the reading of our tests we used the gel
      centrifugation method (ID-Microtyping-System, Fa. Diamed, Bensheim, Germany).
      RESULTS: The highest isoantibody titers were (in 8 charges) 1:32 or 1:64 in the
      Liss-Coombs test. Irregular antibodies were found in 5 IvIg (maximal titer 1:8).
      CONCLUSIONS: Isoantibodies in the IvIg can influence blood group serologic tests.
      With an example of a newborn who had received IvIg we point to the potential
      danger of misinterpretation of a positive direct antiglobulin test after
      administration of IvIg. Therefore we recommend to carry out the direct
      antiglobulin test before administration of IvIg and to examine all eluates after
      a positive direct Coombs test not only with 0 RBCs but also with A or B RBCs of
      the AB0 blood group of the patient.

PMID- 7727962
TI  - Participation of the blood platelet in immune reactions due to platelet
      complement interaction.
AB  - OBJECTIVE: Review of different aspects of the primary interaction of complement
      with blood platelets in immunological reactions and the effect on platelet
      activation in healthy people and patients. DATA SOURCES AND SELECTION CRITERIA:
      Relevant original papers and review articles mainly of the English-written
      literature. RESULTS: Besides their major role in hemostasis and wound healing,
      blood platelets are involved in immunological reactions. They are not only able
      to interact with IgG through Fc receptors (FcR), they also react with complement
      components. This review summarizes interactions of complement with mainly human
      platelets. Such interactions may occur through complement receptors of the plasma
      membrane (e.g. C1q receptor, complement receptors 2 and 4), but also in a
      receptor-independent way including activation of the platelet by the membrane
      attack complex of complement C5b-9. In addition, activation of complement at the
      surface of the platelets may be induced after binding of anti-platelet antibodies
      to membrane glycoproteins (e.g. GpIIb/IIIa, GpIb/IX) or after binding of platelet
      nonspecific immune complexes via FcR. Complement activation in turn may be
      regulated by various means including specific plasma or membrane proteins [e.g.
      decay-accelerating factor (DAF), membrane cofactor protein (MCP), membrane
      inhibitor of reactive lysis (MIRL), C8-binding protein (C8bp, homologous
      restriction factor hrf)]. As a further way of self-protection against complement
      attack, platelets may actively release C5b-9, deposited at the surface as C5b-9
      enriched membrane vesicles. CONCLUSIONS: Two lines of interaction of platelet
      with complement can be distinguished. On the one hand, platelets are equipped
      with membrane proteins which protect them from complement attack against
      themselves. On the other hand, membrane receptors for activated complement
      components as well as for IgG are expressed on the surface, which enable the
      platelet to intervene in immunological reactions. This property varies between
      platelets of different species and needs further investigation also in view of
      the platelet as an intersection between immunology and hemostasis.

PMID- 7727963
TI  - [Comment on Hartl WH, Jauch K-W: Post-aggression metabolism: attempt at
      determining current status].

PMID- 7727964
TI  - [Risk of HIV transmission by blood transfusion].

PMID- 7727965
TI  - [Filtration of blood--useful or necessary?].

PMID- 7727966
TI  - [Prevention of HLA antibody formation in patients with hemato-oncologic diseases
      by using leukocyte depleted blood preparations].
AB  - OBJECTIVE: To determine the effect of transfusion therapy with leukocyte-depleted
      platelet concentrates in comparison to transfusion support with standard platelet
      concentrates on the frequency of HLA alloimmunization in hematologic-oncologic
      patients. DESIGN: Prospective randomized study. SETTING: Institute for
      Transfusion Medicine and Immunohematology at a University Hospital. PATIENTS: 52
      hematologic-oncologic patients randomized in 2 groups. INTERVENTIONS: Exclusive
      substitution with leukocyte-depleted blood components (platelet concentrates and
      packed red cells, filter group) or with standard platelet concentrates and
      leukocyte-depleted packed red cells (control group). Determination of the
      development of HLA antibodies. RESULTS: 27% of the patients in the control group
      (4 out of 15) developed HLA antibodies in contrast to zero patients (0 out of 22)
      in the filter group (p < 0.02). CONCLUSIONS: The results of this comparative
      clinical study show that the consequent and exclusive support with leukocyte
      depleted blood components is an effective approach for prevention of HLA
      alloimmunization in long-term substituted patients.

PMID- 7727967
TI  - [Pathogenesis and diagnosis of polycystic ovary syndrome].
AB  - OBJECTIVE: Growth factors (human growth hormone, HGH; insulin-like growth factor
      I, IGF-I) and insulin were evaluated concerning their pathogenetic significance
      in patients with polycystic ovary syndrome (PCOS). METHODS: Twenty-eight women
      with signs of PCOS were examined; 24 women without signs of PCOS served as
      controls. RESULTS: Women with PCOS showed significantly increased androgen, IGF
      I, insulin and glucose levels, higher glucose concentrations in the oral glucose
      tolerance test and a higher body mass index. The concentration of HGH, the
      HGH/IGF-I ratio and the number of insulin receptors on red blood cells were
      significantly decreased in women with PCOS. The insulin receptor affinity, the
      maximum binding and the insulin-receptor complex were increased in PCOS patients.
      CONCLUSION: A decreased number of insulin receptors, a disturbed insulin receptor
      binding, the resulting hyperinsulinemia as well as high levels of IGF-I are to be
      considered as important factors in the pathogenesis of PCOS.

PMID- 7727968
TI  - [Prevention of neural tube defects by folic acid administration in early
      pregnancy. Joint recommendations of the German Society of Nutrition, Gynecology
      and Obstetrics, Human Genetics, Pediatrics. Society of Neuropediatrics].
AB  - OBJECTIVE: Is folic acid supplementation for the prevention of neural tube
      defects effective? How could periconceptional folic acid supplementation be
      recommended in Germany and actually put into practice? METHODS: Analysis of the
      available literature and of the German health care system. RESULTS: According to
      the available data, it is likely that the rate of neural tube defects can be
      reduced by periconceptional folic acid. Matters of concern regarding its
      practical implementation are: difficulties regarding the information of the
      target group; the presently rare ingestion of vitamin supplements by women of
      child-bearing age in Germany; the lack of suitable folic acid preparations.
      CONCLUSIONS: Several German societies have recommended folic acid supplements for
      women who plan to become pregnant: 4 mg for those at high risk (previous child
      with neural tube defect) and 0.4 mg/daily for women without a particular risk.

PMID- 7727970
TI  - [Persistent ductus omphaloentericus--a possible cause of bleeding umbilicus].
AB  - We report the case of a 23-year-old woman with a persistent omphalomesenteric
      duct. The diagnosis was verified by histology. Further differential diagnoses of
      bleeding umbilicus are the urachal fistula and endometriosis.

PMID- 7727969
TI  - [Gynecologic examination: perceptions, fears and expectations of polyclinic
      patients].
AB  - OBJECTIVE: What kind of expectations, desires and fears do patients have
      concerning the pelvic examination, and is it possible to improve the procedure?
      METHODS: We asked 1,061 women of our gynecological outpatient clinic using a
      questionnaire. RESULTS: 48% said that the pelvic examination caused no problem at
      all, while nearly every third patient felt tense and uncomfortable. 75% of the
      women wanted explanations during the examination, which had to be carried out in
      the absence of a third person in 46%. The same percentage said that it did not
      matter. 53% had no preference of gender concerning the examiner, 37% preferred a
      female doctor and 10% gave preference to a male one. CONCLUSIONS: The pelvic
      examination, which is mainly associated with reluctance and discomfort of the
      patient, does not seem to be experienced like this by almost half of our
      patients. It is easily possible to ameliorate the procedure, for example by
      explaining the findings during the examination and by complying with the gender
      preferences of the patients as much as possible.

PMID- 7727971
TI  - [Systemic methotrexate therapy of persistent trophoblast after tube saving
      surgery for extrauterine pregnancy].
AB  - Is single-drug methotrexate therapy for persistent trophoblastic tissue after
      conservative laparoscopic surgery an effective medical treatment? Here we report
      and discuss a case of apparent persistent trophoblastic tissue after salpingotomy
      and removal of an ectopic pregnancy treated with methotrexate and review the
      published cases. Single drug-therapy with methotrexate is an alternate approach
      to a persistent trophoblast after conservative surgery for ectopic pregnancy.
      Having recently undergone surgery, these women suffer when operated again due to
      anesthesiologic, surgical and psychological stress. The current case and the
      published data demonstrate that methotrexate is a simple, efficacious, successful
      and by now established therapy.

PMID- 7727972
TI  - Management of severe blood loss after tumor resection in a Jehovah's Witness.
AB  - This report describes the peri- and postoperative management of a patient with a
      critical blood loss (hemoglobin of 22 g/l) as a consequence of a surgical
      intervention, i.e. a radical resection of an advanced malignant gynecological
      tumor. The patient refused autologous and homologous blood transfusions for
      religious reasons (Jehovah's Witness). During surgery, hemodilution and cell
      salvage were used. Postoperatively she developed coagulopathy and hemorrhage with
      the lowest hemoglobin value of 22 g/l. The patient recovered under a therapy
      regimen of recombinant human erythropoietin and parenteral iron. The hemoglobin
      values returned to the lower normal range within 4 weeks. Consequences of hypoxia
      could not be seen.

PMID- 7727973
TI  - [Transvaginal ultrasound of "placental-site trophoblastic tumor"].
AB  - The case of a placental-site trophoblastic tumor (PSTT) is described.
      Transvaginal sonography revealed a vascularized tumor mass with a deep invasion
      of the myometrium, partly with echogenic, solid parts and partly multiple echo
      free cystic lesions. The maximum size of an echo-free cystic lesion was 4.4 cm.
      Doppler exploration indicated the presence of blood flow in all these cystic
      lesions. Distinctly abnormal low flow indices were prominent in the whole tumor
      area. According to the clinical results and the slightly positive levels of human
      chorionic beta-gonadotropin (100-1,000 IU/l postpartum), this tumor was
      classified as malignant trophoblastic disease, most likely PSTT. The authors
      conclude that, in the case of a patient with suspected trophoblastic disease and
      in view of the sonographic findings, PSTT may be a valid differential diagnosis,
      particularly if larger cystic lesions of more than 3 cm in diameter are found in
      the tumor bed together with evident blood flow at a low vascular resistance.

PMID- 7727974
TI  - [Gynecologic oncology at the Royal Hospital for Women, Sidney. Report on a 10
      month overseas stay].
AB  - Gynecologic oncology is centralized in Australia. In centers like the Royal
      Hospital for Women in Sydney, more than 300 patients/year with gynecologic
      malignancies are operated on. The establishment of gynecologic oncology as a
      special field is illustrated. In addition, the 3-year training program of
      gynecologic oncologists is reviewed. The international trend towards
      specialization is emphasized, and the advantages of centralization and additional
      training are pointed out. An adaptation of the Australian model for Austrian
      circumstances is proposed.

PMID- 7727975
TI  - [Transgressing the limits of naturopathy].
AB  - Three examples of the tendency of nonconventional medicine to transgress its self
      imposed limits are presented: (1) the efforts of Benveniste to confer scientific
      respectability on homeopathy; (2) the attempt, by press conference, to popularize
      home delivery; (3) the creation of a new demand by the offer of subaquatic
      delivery.

PMID- 7727976
TI  - [Position of the German Society of Gynecology and Obstetrics on the intended
      recall of approved CPA-containing drugs].

PMID- 7727977
TI  - [Current therapy of polycystic ovary].

PMID- 7727978
TI  - [Stimulation therapy as an important therapeutic strategy in treatment of
      sterility].

PMID- 7727979
TI  - [Ovulation induction in general practice--possibilities and limits].

PMID- 7727980
TI  - [Histologic changes in ligated stumps of ovarian blood vessels in preoperative
      low-molecular weight preventive heparin administration].
AB  - OBJECTIVE: Thrombotic changes and vascular lesions during adnexectomy were
      observed. We resected the stumps of the ovarian blood vessels after 30 min.
      METHODS: Two hours before surgery we injected a dosis of 20 mg Lovenox s.c.
      Special histological methods of coloring were used. RESULTS: We found evidence of
      only parietal thrombus formation 3 times (10%) in the arteries and 4 times
      (13.3%) in the veins; the endothelial damage was reduced. CONCLUSIONS: Low
      molecular-weight heparin is most effective and safe in the prevention of
      thrombogenesis. We definitively replaced the "old" standard heparin in clinical
      gynecological practice.

PMID- 7727981
TI  - On designing integrated quality oversight policy.

PMID- 7727982
TI  - Total quality management of a medical residency.
AB  - Although many hospitals have begun the long and difficult process of adapting to
      the concepts of total quality management, few have reported efforts to apply
      total quality management to a medical residency. We report here the initial
      results of the Western Pennsylvania Hospital's efforts, as part of the hospital's
      conversion of its management structure to total quality management.

PMID- 7727983
TI  - The July phenomenon revisited: are hospital complications associated with new
      house staff?
AB  - This study was designed to investigate the relationship between the clinical
      experience of resident physicians and quality of care. This investigation was
      done by examining the month of the year when patients were treated by resident
      physicians and a comprehensive set of quality indicators. Quality of care was
      assessed by a severity-weighted index of adverse events consisting of 47 quality
      indicators that were screened from 28,541 medical records during a 12-month
      period. Hospital-wide results indicate that there was no overall relationship
      between the house officers experience and severity-adjusted adverse events, with
      the exception of one surgical department that had a higher index of adverse
      events in the first part of the academic year. Although this study finds no
      support for a "July Phenomenon" in terms of quality of clinical care, house
      officers were found to be more likely to have poor documentation practices
      earlier in the academic year.

PMID- 7727984
TI  - The effectiveness of Medicare Part B medical review: issues and alternatives.
AB  - The part B medical review methods currently used by Medicare carriers to control
      resource use suffer from a series of problems including failure to reward
      deterrence of unnecessary claims, failure to detect substitution of nonreviewed
      claims, reliance on average rather than marginal measures of performance,
      excessive focusing of reviews, and the inability to measure effectiveness
      separately from the intervention. This article describes these problems and
      proposes a series of alternative strategies for review that may improve these
      problems.

PMID- 7727985
TI  - Postoperative adverse events of cholecystectomy in the Medicare population.
AB  - We explored the use of postoperative adverse events of cholecystectomy as
      possible screens for poor quality of care. Retrospective analysis of clinical
      data abstracted from hospital charts between 1985-1986 was conducted on a random
      sample of 3,182 cholecystectomy cases. Severity of illness models were developed
      predicting adverse events following cholecystectomy in patients with and without
      bile duct exploration. Outcome measures included 17 nonfatal adverse events and
      death within 30 days of admission. Adverse event rates were 23.2% for cases with
      bile duct exploration and 14.4% for cases without bile duct exploration. Cross
      validated R-squareds and C-statistics showed that models had real, although
      modest, predictive power. We conclude that clinically meaningful adverse events
      of cholecystectomy can be successfully identified through chart abstraction.

PMID- 7727986
TI  - Quality in the interorganizational setting.
AB  - For many patients, important health services are delivered by a process of care
      that spans several service organizations. Issues influencing the quality of care
      delivered across organizations are infrequently discussed in the health care
      quality literature. In this paper, interorganizational quality problems that
      detract from the care received by children with spina bifida, lead poisoning, and
      children who have been sexually abused are identified. Using concepts from the
      organizational behavior literature, both structural and group process approaches
      to addressing these problems are discussed to enhance the care received by
      children. A broader conceptualization of care delivery is required if patients
      whose care spans institutions are to benefit from quality improvement efforts.

PMID- 7727987
TI  - Carotid endarterectomy clinical pathway: an innovative approach.

PMID- 7727988
TI  - Costs of potential complications of care for major surgery patients.
AB  - We examined computerized hospital discharge abstract data from 372,680 major
      surgery patients admitted to 404 California acute care hospitals in 1988 to
      identify potential complications of care. At least one potential in-hospital
      complication occurred for 10.8% of patients. Patients with complications were
      older and more likely to die in-hospital (9.4% compared to 1.0%, P < 0.0001). On
      average, patients with complications had longer stays (13.5 versus 5.4 days, p <
      0.0001) and higher total charges ($30,896 versus $9,239, p < 0.0001). After
      adjusting for demographic, clinical, and hospital factors, patients with
      potential complications averaged $16,023 higher total hospital charges than
      uncomplicated patients. Complications were associated with 96.6% (95% confidence
      interval = 95.2%, 98.0%) higher hospital charges after adjusting for these
      factors. Across all patients, complications were related to over $647 million in
      additional total hospital charges for these major surgery patients.

PMID- 7727989
TI  - Uproar over confidentiality in New Zealand.

PMID- 7727990
TI  - Screening for breast cancer. Incidence of interval cancer and detection rate of
      first screenings are inconsistent.

PMID- 7727991
TI  - Screening for breast cancer. Recommendations are costly and short sighted.

PMID- 7727992
TI  - Screening for breast cancer. Maximise compliance as well as radiological
      sensitivity.

PMID- 7727993
TI  - Screening for breast cancer. British women are being offered a cheap deal.

PMID- 7727994
TI  - Screening for breast cancer. Informed consent may increase non-attendance rate.

PMID- 7727995
TI  - Screening for breast cancer. Technicians could be trained to interpret screening
      mammograms.

PMID- 7727996
TI  - Screening for the breast cancer. Has increased the workload for primary care
      teams.

PMID- 7727997
TI  - Uptake of breast screening. Accurate addresses will improve uptake rates.

PMID- 7727998
TI  - Uptake of breast screening. May be influenced by practice specific factors.

PMID- 7727999
TI  - Uptake of breast screening. Non-responders can be encouraged to attend.

PMID- 7728000
TI  - Acyclovir and post-herpetic neuralgia. The balance of available evidence supports
      its use.

PMID- 7728001
TI  - Acyclovir and post-herpetic neuralgia. Two other participating study centres
      report different results.

PMID- 7728002
TI  - Needs are never demands.

PMID- 7728003
TI  - Services for cleft lip and palate. All patients should have access to plastic
      surgery.

PMID- 7728004
TI  - Computed tomography in first uncomplicated generalised seizure. Should always be
      performed.

PMID- 7728005
TI  - Computed tomography in first uncomplicated generalised seizure. Should be
      performed irrespective of any history of alcohol misuse.

PMID- 7728006
TI  - Computed tomography in first uncomplicated generalised seizure. Is grossly
      oversold.

PMID- 7728007
TI  - Thrombolysis in patients with diabetes. More evidence that the treatment should
      not necessarily be withheld.

PMID- 7728008
TI  - Thrombolysis in patients with diabetes. Prophylaxis with aspirin should be
      considered.

PMID- 7728009
TI  - Thrombolysis in patients with diabetes. Mersey has changed its policy.

PMID- 7728010
TI  - Thrombolysis in patients with diabetes. Risk of intraocular haemorrhage remains
      unknown.

PMID- 7728011
TI  - Non-insulin dependent diabetes mellitus and non-Hodgkin's lymphoma. Other
      American studies fail to confirm an association.

PMID- 7728012
TI  - Rationing intensive care. Crisis reactions to shortages should be replaced by
      analysis of strategic services.

PMID- 7728013
TI  - Miracle cure [corrected].

PMID- 7728014
TI  - Rationing intensive care. High dependency units may be the answer.

PMID- 7728015
TI  - Failure of consultant expansion.

PMID- 7728016
TI  - Rationing intensive care. Neurosurgical intensive care in the south east.

PMID- 7728017
TI  - Education and dementia.

PMID- 7728018
TI  - Hospital doctors' work.

PMID- 7728019
TI  - Consultants of the future.

PMID- 7728020
TI  - Tuberculosis: old reasons for a new increase?

PMID- 7728021
TI  - Promoting cost effective prescribing.

PMID- 7728022
TI  - Researchers in US dispute first case of AIDS.

PMID- 7728023
TI  - AIDS strategy must pay more attention to human rights.

PMID- 7728024
TI  - Ireland deals with hepatitis C fallout.

PMID- 7728026
TI  - Doctors highlight Australia's youth suicide problem.

PMID- 7728025
TI  - Report of French "blood scandal" is leaked to press.

PMID- 7728027
TI  - Hospital banned from doing neonatal heart operations.

PMID- 7728028
TI  - Medicare trustees call for spending curbs.

PMID- 7728029
TI  - France dilutes tobacco and alcohol advertising ban.

PMID- 7728030
TI  - Socioeconomic deprivation and notification rates for tuberculosis in London
      during 1982-91.
AB  - OBJECTIVES: To investigate the association between four sociodemographic measures
      (unemployment, overcrowding, low social class, and the proportion of migrants
      from areas of high prevalence of tuberculosis) and average level and rate of
      change of notification rates for tuberculosis. DESIGN: Ecological analysis of
      both the average and the rate of change of standardised annual notification rates
      for tuberculosis from 1982-91 and sociodemographic measures from the 1981 and
      1991 censuses. SETTING: 32 London boroughs. SUBJECTS AND DATA: Sociodemographic
      measures from the 1981 and 1991 censuses and tuberculosis notification rates for
      1982-91. MAIN OUTCOME MEASURES: A measure of the association between average
      levels and rate of change in tuberculosis notification rates and four
      sociodemographic measures in 1981 and between the rate of change in tuberculosis
      notification rates between 1981 and 1991 and changes in sociodemographic measures
      between 1981 and 1991. RESULTS: The average level of notifications was correlated
      with overcrowding and the proportion of migrants but not with unemployment or
      social class. No significant association was found between the rate of change in
      notification rates and sociodemographic measures in 1981. An association was
      found between increases in unemployment and the rate of change in notification
      rates, but the effect was small. Changes in the levels of unemployment explained
      23% of the variation between boroughs in the rate of change in their notification
      rates. CONCLUSION: The average tuberculosis notification rates were related to
      overcrowding and the proportion of migrants in 1981. Only increases in
      unemployment from 1981 to 1991, however, were significantly associated with the
      rate of change in notifications over the same period.

PMID- 7728031
TI  - Increasing incidence of tuberculosis in England and Wales: a study of the likely
      causes.
AB  - OBJECTIVE: To examine factors responsible for the recent increase in tuberculosis
      in England and Wales. DESIGN: Study of the incidence of tuberculosis (a) in the
      403 local authority districts in England and Wales, ranked according to Jarman
      score, and (b) in one deprived inner city district, according to ethnic origin
      and other factors. SETTING: (a) England and Wales 1980-92, and (b) the London
      borough of Hackney 1986-93. MAIN OUTCOME MEASURE: Age and sex adjusted rate of
      tuberculosis. RESULTS: In England and Wales notifications of tuberculosis
      increased by 12% between 1988 and 1992. The increase was 35% in the poorest 10th
      of the population and 13% in the next two; and in the remaining 70% there was no
      increase. In Hackney the increase affected traditionally high risk and low risk
      ethnic groups to a similar extent. In the "low risk" white and West Indian
      communities the incidence increased by 58% from 1986-8 (78 cases) to 1991-3
      (123), whereas in residents of Indian subcontinent origin the increase was 41%
      (from 51 cases to 72). Tuberculosis in recently arrived immigrants--refugees (11%
      of the Hackney population) and Africans (6%)--accounted for less than half of the
      overall increase, and the proportion of such residents was much higher than in
      most socioeconomically deprived districts. The local increase was not due to an
      increase in the proportion of cases notified, to HIV infection, nor to an
      increase in homeless people. CONCLUSIONS: The national rise in tuberculosis
      affects only the poorest areas. Within one such area all residents (white and
      established ethnic minorities) were affected to a similar extent. The evidence
      indicates a major role for socioeconomic factors in the increase in tuberculosis
      and only a minor role for recent immigration from endemic areas.

PMID- 7728032
TI  - Prevalence of Alzheimer's disease and vascular dementia: association with
      education. The Rotterdam study.
AB  - OBJECTIVE: To estimate the prevalence of dementia and its subtypes in the general
      population and examine the relation of the disease to education. DESIGN:
      Population based cross sectional study. SETTING: Ommoord, a suburb of Rotterdam.
      SUBJECTS: 7528 participants of the Rotterdam study aged 55-106 years. RESULTS:
      474 cases of dementia were detected, giving an overall prevalence of 6.3%.
      Prevalence ranged from 0.4% (5/1181 subjects) at age 55-59 years to 43.2% (19/44)
      at 95 years and over. Alzheimer's disease was the main subdiagnosis (339 cases;
      72%); it was also the main cause of the pronounced increase in dementia with age.
      The relative proportion of vascular dementia (76 cases; 16%), Parkinson's disease
      dementia (30; 6%), and other dementias (24; 5%) decreased with age. A
      substantially higher prevalence of dementia was found in subjects with a low
      level of education. The association with education was not due to confounding by
      cardiovascular disease. CONCLUSIONS: The prevalence of dementia increases
      exponentially with age. About one third of the population aged 85 and over has
      dementia. Three quarters of all dementia is due to Alzheimer's disease. In this
      study an inverse dose-response relation was found between education and dementia-
      in particular, Alzheimer's disease.

PMID- 7728033
TI  - Severity of heart failure and dosage of angiotensin converting enzyme inhibitors.

PMID- 7728034
TI  - Improving notification rates for tuberculosis.

PMID- 7728035
TI  - Do doctors accurately assess coronary risk in their patients? Preliminary results
      of the coronary health assessment study.
AB  - OBJECTIVE: To evaluate the ability of doctors in primary care to assess risk
      patients' risk of coronary heart disease. DESIGN: Questionnaire survey. SETTING:
      Continuing medical education meetings, Ontario and Quebec, Canada. SUBJECTS:
      Community based doctors who agreed to enroll in the coronary health assessment
      study. MAIN OUTCOME MEASURE: Ratings of coronary risk factors and estimates by
      doctors of relative and absolute coronary risk of two hypothetical patients and
      the "average" 40 year old Canadian man and 70 year old Canadian woman. RESULTS:
      253 doctors answered the questionnaire. For 30 year olds the doctors rated
      cigarette smoking as the most important risk factor and raised serum triglyceride
      concentrations as the least important; for 70 year old patients they rated
      diabetes as the most important risk factor and raised serum triglyceride
      concentrations as the least important. They rated each individual risk factor as
      significantly less important for 70 year olds than for 30 year olds (all risk
      factors, P < 0.001). They showed a strong understanding of the relative
      importance of specific risk factors, and most were confident in their ability to
      estimate coronary risk. While doctors accurately estimated the relative risk of a
      specific patient (compared with the average adult) they systematically
      overestimated the absolute baseline risk of developing coronary disease and the
      risk reductions associated with specific interventions. CONCLUSIONS: Despite
      guidelines on targeting patients at high risk of coronary disease accurate
      assessment of coronary risk remains difficult for many doctors. Additional
      strategies must be developed to help doctors to assess better their patients'
      coronary risk.

PMID- 7728036
TI  - Treating myopia with the excimer laser: the present position.

PMID- 7728037
TI  - The rhetoric of research.

PMID- 7728038
TI  - Commentary: scientific heads are not turned by rhetoric.

PMID- 7728039
TI  - ABC of rheumatology. Osteoporosis.

PMID- 7728040
TI  - Time to leave behind genocidal weapons.

PMID- 7728041
TI  - Continuing medical education: a personal view.
AB  - Over many generations doctors have kept up to date in ways which reflect their
      own learning styles. The current fashion for formalised and policed continuing
      medical education may prove ineffective unless it is recognised that individual
      needs must be taken into account. Attendance at formal courses based on lectures
      and papers may not suit a large proportion of those who attend to acquire the
      necessary points to satisfy their royal college. The ability to show that health
      care teams are up to date should come from effective clinical audit, which should
      also identify local educational needs.

PMID- 7728042
TI  - The importance of quality: sharing responsibility for improving patient care.

PMID- 7728043
TI  - Unified training grade.

PMID- 7728044
TI  - Toxoplasma and the eye.

PMID- 7728045
TI  - Radiation and women of child bearing potential.

PMID- 7728046
TI  - Should herbal medicine-like products be licensed as medicines.

PMID- 7728047
TI  - New draft on European directive on confidential data.

PMID- 7728048
TI  - Germany's home care scheme faces problems.

PMID- 7728049
TI  - Abortion issue goes to US courts.

PMID- 7728050
TI  - Australia launches major study of women's health.

PMID- 7728051
TI  - Report urges better psychological care.

PMID- 7728052
TI  - Tropical diseases move north with global warming.

PMID- 7728053
TI  - Dutch court convicts doctor of murder.

PMID- 7728054
TI  - The French way of controlling drug costs.

PMID- 7728055
TI  - Health and cancer prevention: knowledge and beliefs of children and young people.
AB  - OBJECTIVE: To collect information from children and young people about their
      knowledge of and attitudes towards cancer and their understanding of health and
      health related behaviours to inform future health promotion work. DESIGN:
      Questionnaire survey of 15-16 year olds, and interviews with play materials with
      9-10 year old children. SETTING: Six inner city, suburban, and rural schools.
      SUBJECTS: 226 children aged 15-16 years and 100 aged 9-10 years. MAIN OUTCOME
      MEASURES: Knowledge about different types of cancer; beliefs about health;
      sources of information; quality of research data obtainable from young children
      about cancer and health. RESULTS: Both samples knew most about lung cancer, but
      there was also some knowledge of breast and skin cancer and leukaemia. Smoking,
      together with pollution and other environmental factors, were seen as the
      dominant causes of cancer. Environmental factors were mentioned more often by the
      inner city samples. Television and the media were the most important sources of
      information. Young people were more worried about unemployment than about ill
      health. More than half the young people did not describe their health as good,
      and most said they did not have a healthy lifestyle. Children were able to
      provide detailed information about their knowledge and understanding by using
      drawings as well as interviews. CONCLUSIONS: Children and young people possess
      considerable knowledge about cancer, especially about lung cancer and smoking,
      and show considerable awareness of predominant health education messages. Despite
      this knowledge, many lead less than healthy lifestyles. Health is not seen as the
      most important goal in life by many young people; the circumstances in which many
      children and young people live are not experienced as health promoting.

PMID- 7728056
TI  - Multicentre study of cancer pain and its treatment in France.
AB  - OBJECTIVE: To describe the treatment of cancer pain in France and to evaluate the
      predictive factors for inadequate management. DESIGN: Multicentre, representative
      cross sectional survey. SETTING: 20 treatment centres, including cancer centres,
      university hospitals, state hospitals, private clinics, and one homecare setting
      (in which patients are supported at home). SUBJECTS: 605 patients with cancer.
      MAIN MEASURES: Patients rated prevalence and severity of pain and functional
      impairment related to pain. Doctors reported patients' cancer characteristic,
      performance status, pain severity, and analgesic drugs ordered. RESULTS: 57%
      (340/601) of patients with cancer reported pain due to their disease, and, of
      those with pain, 69% (224/325) rated their worst pain at a level that impaired
      their ability to function. 30% (84/279) were reported as receiving no drugs for
      their pain. Of the 270 patients in pain for whom information on treatment was
      available 51% (137/270) were not receiving adequate pain relief, according to an
      index based on the World Health Organisation's guidelines. French doctors were
      found to underestimate the severity of their patients' pain. Younger patients,
      patients without metastatic disease, patients with a better performance status,
      and patients who rated their pain as more severe than their doctors did were at
      greater risk for undertreatment of their pain. CONCLUSIONS: In the light of the
      high prevalence and the severity of pain among patients with cancer, the
      assessment and treatment of cancer pain in France remain inadequate, emphasising
      the need for changes in patient care.

PMID- 7728057
TI  - Incidence of acute symptomatic toxoplasma retinochoroiditis in south London
      according to country of birth.
AB  - OBJECTIVE: To determine the incidence of acute symptomatic toxoplasma
      retinochoroiditis presenting to ophthalmologists for patients born in Britain and
      elsewhere. DESIGN: Population based, cross sectional study. SETTING: 11 districts
      in south Greater London. SUBJECTS: All patients presenting to NHS
      ophthalmologists with symptoms due to acute toxoplasma retinochoroiditis in 1992
      3. MAIN OUTCOME MEASURE: Intraocular inflammation in association with a
      retinochoroidal scar, active adjoining retinitis, and IgG serum antibodies to
      toxoplasma. RESULTS: The estimated incidence of acute symptomatic
      retinochoroiditis for all people born in Britain was 0.4/100,000/year. If a mean
      of two symptomatic episodes per lifetime is assumed, 100 people born in Britain
      may be affected each year, about a fifth of the estimated 500-600 congenitally
      infected people born each year. CONCLUSIONS: A substantial proportion of people
      with acute symptomatic toxoplasma retinochoroiditis were born outside the
      country, and the number born in Britain was smaller than the number previously
      estimated to develop retinochoroidal lesions due to congenital toxoplasmosis.
      These findings suggest that prenatal screening for toxoplasmosis in Britain may
      be of limited benefit.

PMID- 7728058
TI  - Randomised clinical trial of ultrasound treatment for pressure ulcers.

PMID- 7728059
TI  - The wizard and the gatekeeper: of castles and contracts.
AB  - The wizards and the gatekeepers were unhappy. There were many reasons for their
      unhappiness. They worked hard but felt that too much was being demanded of them.
      The poorly people's charter was resulting in unrealistic expectations, and
      changes in the apprenticeship for wizards were putting great strain on their
      mentors. The wizards enjoyed their work less and less, and it was getting
      difficult to find new gatekeepers. On the other hand, the way the system worked
      meant that there had to be plenty of goblins and the number of scrolls that had
      to be filled in was rising sharply. The wizards and gatekeepers tried to point
      out ways to improve things that would ensure that poorly people were better
      treated, but there was no easy solution. With the ominous sign that the
      recruitment of wizards and gatekeepers was becoming more difficult, an answer was
      needed--and soon.

PMID- 7728060
TI  - NHS "indicators of success": what do they tell us? Radical Statistics Health
      Group.
AB  - In the absence of any systematic evaluation of the changes it has made to the
      NHS, the government cites three "indicators of success." These are record numbers
      of patients treated, shorter waiting times for hospital treatment, and more
      children being immunised against the main childhood diseases. Closer inspection
      of the statistics reveals that they do not support the conclusions inferred from
      them and that they are misleading measures of the impact of the changes made to
      the NHS.

PMID- 7728061
TI  - Vitamin A deficiency and xerophthalmia in the United Kingdom.

PMID- 7728062
TI  - On a front line.
AB  - Like the patients, doctors in Sarajevo depend largely on humanitarian aid;
      everyone in the public sector has worked without pay for almost three years. The
      hospital is on a front line; yet the psychiatric department continues to
      function, even conducting large scale studies of psychosocial aspects of war in
      Bosnia-Hercegovina. The type of inpatient morbidity and treatment patterns have
      changed. A plethora of psychosocial rehabilitation programmes has emerged,
      including counselling, drop in centres, and attending to special needs of elderly
      people, schoolchildren, and women. The most prominent psychological symptoms were
      exhaustion at the prospect of a third winter of war and bewilderment at the
      Western stereotype of Bosnians as Muslim fundamentalists.

PMID- 7728063
TI  - Handling the conflicting cultures in the NHS.

PMID- 7728064
TI  - ABC of rheumatology. Polymyalgia rheumatica and giant cell arteritis.

PMID- 7728065
TI  - Bronchiolitis. Home observation is inadvisable.

PMID- 7728066
TI  - Bronchiolitis. Isolated pulse oximetry readings are unreliable.

PMID- 7728067
TI  - Bronchiolitis. Tribavirin may be helpful.

PMID- 7728068
TI  - Bullying in schools. A more aggressive preventive strategy is required.

PMID- 7728069
TI  - Assessing the consequences of changing childbirth. General practitioners collect
      valuable data.

PMID- 7728070
TI  - Bullying in schools. Accident and emergency departments need management
      guidelines.

PMID- 7728071
TI  - Assessing the consequences of changing childbirth. Smart cards are expensive and
      easily damaged.

PMID- 7728072
TI  - Management of the irritable bowel syndrome. Early reassurance is important part
      of treatment.

PMID- 7728073
TI  - Management of the irritable bowel syndrome. Food intolerance may play a part.

PMID- 7728074
TI  - Proposed new deprivation index. May perpetuate variation in prescribing unrelated
      to patients' need.

PMID- 7728075
TI  - Proposed new deprivation index. Poor correlation with Jarman index may be due to
      changes in deprivation since 1981.

PMID- 7728076
TI  - Academic integrity. Proper review makes funding irrelevant.

PMID- 7728077
TI  - Academic integrity. Most people are not disgusted by the Portman group.

PMID- 7728078
TI  - Appropriate prescribing in asthma. PACT data have drawbacks.

PMID- 7728079
TI  - Appropriate prescribing in asthma. Cost and cost effectiveness are different.

PMID- 7728080
TI  - Appropriate prescribing in asthma. Good prescribing is encouraged.

PMID- 7728081
TI  - Bottle feeding and the sudden infant death syndrome. Study was not large enough
      to show effect.

PMID- 7728082
TI  - Bottle feeding and the sudden infant death syndrome. Type of formula was not
      specified.

PMID- 7728083
TI  - Sudden infant death in France.

PMID- 7728084
TI  - Sampling for analysing blood gas pressures. Arterial samples are the best.

PMID- 7728085
TI  - Geographical relations between patients and general practitioners.

PMID- 7728086
TI  - Paracetamol and self poisoning.

PMID- 7728087
TI  - Sampling for analysing blood gas pressures. Capillary sampling is routine in
      Germany.

PMID- 7728088
TI  - Preventing suicide.

PMID- 7728089
TI  - Multiple significance tests.

PMID- 7728090
TI  - Referencing medical articles on computer networks.

PMID- 7728091
TI  - The Gulf War syndrome.

PMID- 7728092
TI  - Highlights of the Eighteenth Annual Meeting of the American Society of Preventive
      Oncology; Bethesda, MD, USA, 6-9 March 1994.

PMID- 7728093
TI  - A healthy company: enhanced competitiveness through a healthy workforce Berlin,
      Germany, 29-30 September 1994.

PMID- 7728094
TI  - What is health promotion? How does it relate to the workplace? A background paper
      to support the Conference in Berlin on 29-30 September, 1994.
AB  - Can workplaces be successful health promotion settings? Undoubtedly they can, in
      both direct and indirect ways. Directly, in being cost effective for companies,
      and indirectly, in improving the health and well being of all who work in a
      company. Under European directives the workplace has a responsibility to promote
      health promotion: this goes beyond health and safety, and protection of the
      workforce. Using WHO healthy policy principles, workplaces can be seen as a
      microcosm of society and therefore the principles of health promoting policies
      can be used to encourage healthy companies.

PMID- 7728095
TI  - Alcohol in the Mediterranean diet: assessing risks and benefits.

PMID- 7728096
TI  - Epidemiological evidence on hair dyes and the risk of cancer in humans.
AB  - Epidemiological data on occupational exposure and personal use of hair dyes was
      reviewed with specific focus on bladder cancer and lymphoid neoplasms. At least
      seven cohort and 11 case-control studies included data on occupational exposure
      to hair dyes by hairdressers, barbers and beauticians, and their subsequent
      bladder cancer risk. The relative risk (RR) estimate was 1.4 (183 observed vs 129
      expected) for cohort studies, and in several case-control studies the RRs were
      somewhat above unity. These results are compatible with some moderate association
      between past professional exposure to hair dyes and subsequent bladder cancer
      risk, but also with errors and biases in observational epidemiological studies,
      particularly since allowance for smoking was lacking or inadequate in most
      studies. An open question is whether current occupational exposure to modern hair
      dyes is still related to some excess bladder cancer risk. Five case-control
      studies included information on personal use of hair dyes and bladder cancer
      risk. There was no evidence of any association. Nine cohort and eight case
      control studies considering occupational exposure to hair dyes and lymphoid
      neoplasms were reviewed. In the cohort studies, a total of 100 lymphoid neoplasms
      was observed compared with 84.4 expected (RR 1.2). The RR estimates were 1.5 for
      non-Hodgkin's lymphomas (NHL, 17 observed vs 11.2 expected) and 1.1 for multiple
      myeloma (MM, 19 observed cases vs 16.8 expected). Interpretation of case-control
      studies of occupational exposure is seriously hampered by the small number of
      exposed cases. Five case-control studies considered personal use of hair dyes and
      the risk of lymphoid neoplasms. Of these, three reported some association,
      particularly with NHL and MM. However, the RR estimates were only moderately
      above unity, and inadequate allowance was made for potential confounding factors,
      including social class and greying hair, which could be correlates of both hair
      dye use and lymphoid neoplasms. Further, there is little information on the
      biodistribution and bioavailability of potential carcinogens in hair dyes,
      particularly their concentrations in lymphoid tissue. These findings, therefore,
      require further research, particularly since they may be influenced by selective
      publication of positive findings (publication bias). None of the other neoplasms
      extensively studied, including breast, skin and lung was related to hair dye use.

PMID- 7728097
TI  - Role of schistosomiasis in human bladder cancer: evidence of association,
      aetiological factors, and basic mechanisms of carcinogenesis.
AB  - Several epidemiological, clinical and experimental studies have been carried out
      to determine whether there is an aetiological role for schistosomiasis in the
      multi-stage process of bladder carcinogenesis. Lines of evidence supporting the
      association between bladder cancer and schistosomiasis include indications from
      the geographical correlation between the two conditions, the distinctive patterns
      of gender and age at diagnosis, the clinicopathological identity of schistosome
      associated bladder cancer and the extensive experimental evidence in infected
      laboratory animals. Although the causative role of schistosomiasis is now
      accepted, various associated factors have been proposed in the induction of this
      particular type of cancer. While all may contribute to the carcinogenic process
      taking place in the infected bladder, none of these has yet been confirmed. Most
      attention has been directed at theories proposing possible roles for urinary
      chemical carcinogens, particularly tryptophan metabolites, N-nitroso compounds
      and of beta-glucuronidase, as factors that are primarily involved in the
      initiation of bladder carcinogenesis in areas endemic for schistosomiasis.

PMID- 7728098
TI  - Breast self-examination: attitudes and practices among young women in Europe.
AB  - Breast self examination (BSE) is recommended for the early detection of breast
      cancer in the European Code against Cancer. Evidence from North America suggests
      that there is reasonable public awareness of its importance, but compliance with
      regular BSE is reported by only a minority of young women. Attitudes to and
      practice of BSE has rarely been studied outside North America. In the present
      study, attitudes to BSE were evaluated by questionnaire in a sample of 16,486
      students aged 17-30 from 20 European countries. Frequency of BSE practice was
      reported by the 9,181 women in the sample. Information on public recommendations
      concerning BSE was obtained from cancer organizations in each country. The data
      were collected as part of the European Health Behaviour Survey, an international
      study on health beliefs and health behaviour. The results showed that BSE was
      recommended in 16 countries and 'breast awareness' in two, while two countries
      did not recommend self-examination. 54% of women reported as never having
      practiced BSE. Regular practice (monthly) was reported by only 8% of the sample,
      with another 36% reporting occasional BSE. Significant differences emerged
      between centres in different countries ranging from 6% to 15% reporting regular
      BSE. Attitude towards BSE was a significant predictor of BSE practice within each
      centre and across all centres combined. Attitudes towards BSE were significantly
      less positive in the two centres from countries without BSE recommendations than
      in the others, but levels of practice were similar.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7728099
TI  - Number of siblings and subsequent gastric cancer risk.
AB  - The number of siblings is an indirect indicator of living and, possibly, dietary
      conditions in childhood and adolescence. The relationship between the number of
      siblings and subsequent gastric cancer risk was analysed using data from a case-
      control study conducted in Italy between 1985 and 1992 on 723 cases of incident,
      histologically confirmed gastric cancer and 2,024 controls in hospital for acute,
      non-neoplastic, non-digestive tract disorders. After allowance for age and sex,
      there was a significant trend of increasing gastric cancer risk with increasing
      number of siblings (P < 0.01). Compared with subjects with no siblings, the
      relative risk (RR) was 1.1 for those with one, 1.3 for 2, 1.4 for 3-6 and 1.7 for
      7 or more siblings. The association was stronger in subjects above the age of 60:
      the RR for > or = 5 siblings was 1.8, as compared with 1.2 for younger subjects.
      These patterns of trends are consistent with the hypothesis that domestic
      crowding and deprivation in childhood and adolescence is a correlate of
      subsequent gastric cancer risk, and offer therefore interesting clues to our
      understanding of the process of gastric carcinogenesis.

PMID- 7728100
TI  - Prevalence of Helicobacter pylori infection and gastritis among young adults in
      China.
AB  - To investigate the prevalence of gastritis and H. pylori infection among young
      Chinese in Henan Province, a high incidence area for oesophageal cancer in China,
      the gastric mucosa was examined in 194 asymptomatic subjects, aged 15-26 years,
      in the course of an epidemiological study of precursor lesions of oesophageal
      cancer. Histopathological grading of gastritis and determination of H. pylori
      infection were performed on haematoxylineosin and Warthin-Starry stained section.
      An enzyme-linked immunosorbent assay was used to detect the presence of serum IgG
      antibodies to H. pylori. A very high prevalence of gastritis (93.8%) was found:
      71 subjects (36.6%) presented with superficial gastritis (14 active), 94 (48.5%)
      with diffuse gastritis (92 active) and in 17 cases (8.8%) diffuse gastritis (16
      active) was accompanied by focal atrophy. Silver staining detected H. pylori in
      166 (85.6%) of the study participants. However, serological techniques identified
      H. pylori in only 109 (56.2%). H. pylori was seen in all the 119 cases showing
      histological signs of active gastritis, in 41 of the 63 cases (65%) without
      activity, and also in 50% (6/12) of histologically normal subjects. H. pylori
      infection was found to be associated with a 2.5-fold higher prevalence of chronic
      atrophic gastritis compared with non-atrophic gastritis. A family history of
      stomach cancer, consumption of pickled vegetables more than twice a month, and a
      high monthly salt consumption (> 500 g/month) also showed a positive
      association.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728101
TI  - Cancer risks among male farmers in Sweden.
AB  - We have conducted a cohort study of cancer risks among 140,208 Swedish farmers in
      order to compare their cancer risks with those of the general male population.
      Since there were no individual data regarding exposure to agricultural chemicals
      and acquiring such data was not realistic, we obtained crude and hypothetical
      estimates for exposure by dividing the data into time periods, year-of-birth
      cohorts and geographical areas. The cohort was followed-up in the Cancer
      Environment Register from 1 January 1971 either until death or until 31 December
      1987. The relative risk was computed as the ratio of the observed and expected
      number of cases (SIR = standardized incidence ratio). A total of 15,040 cases
      were observed vs 18,918 expected, resulting in a statistically significant
      decreased SIR of 0.80 (95% confidence interval: 0.78-0.81). The SIR was
      significantly decreased for several cancer sites, and the lowest value was found
      for tongue, lung, oesophagus, liver and urinary organs, which is in agreement
      with other studies on cancer risks among farmers. Other major cancer sites with
      decreased SIRs were the colon, rectum, pancreas and kidney. Lip cancer and
      multiple myeloma showed statistically significant increased risks. SIRs for
      stomach cancer, prostate cancer, skin carcinoma, malignant melanoma, tumours in
      connective tissue or muscle, malignant lymphomas and leukaemia were all close to
      unity, which is not consistent with several other studies that have shown
      increased risks for these sites. For malignant lymphomas the SIR increased over
      time, though not significantly, and was highest among younger farmers. The SIR
      for non-Hodgkin lymphoma was lowest in the northernmost region. This gives some
      support to the hypothesis that there is an association between non-Hodgkin
      lymphoma and exposure to pesticides and other agricultural chemicals. It is of
      note that the SIR for multiple myeloma was significantly increased in those parts
      of Sweden where the use of pesticides has been less frequent and in lower
      amounts.

PMID- 7728102
TI  - Stop the natural experimental trial in breast cancer because of rising incidence:
      summarizing the evidence.
AB  - A survey has been conducted during the past decade (starting in 1980) of reported
      new cases of women with breast cancer, in order to assess the interim evidence of
      the natural experiment of the effect of increased use of condoms on the risk of
      breast cancer in the US. Age-adjusted incidence rates of breast cancer (to the
      world standard population) per 100,000 population, and trends of changes, in
      percentages, were used. Prior to the 1980s, breast cancer incidence was in
      decline in seven out of 13 centres in the country. Following the recommendations
      to use condoms in 'safer sex' campaigns, increases of breast cancer incidence
      were recorded during the 1980s, as a reflection of a global phenomenon. Between
      the 5 year periods of 1978-82 and 1983-87, the population of the nine
      Surveillance, Epidemiology and End Results programme (SEER) centres (about 10% of
      the American population), increased by 2.9%, the number of breast cancer cases
      increased by 25.0%; the average annual breast cancer crude incidence rose by
      21.5% (from 100.8 to 122.5 per 100,000). The increase in the average annual
      number of breast cancer cases during the period 1983-87 (the period of increased
      condom usage) was 4.5 times greater than that during the preceding period, 1978
      82. During the 1980s, breast cancer trends rose significantly in the US among
      White women (P < 0.00001) and other ethnic groups (P < 0.005). The difference
      between the expected, 21%, and observed, 79%, probability of adverse effects
      occurring in the natural experimental trial was statistically significant (P =
      0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728103
TI  - Laser sclerostomy ab externo using two different infrared lasers: a clinical
      comparison.
AB  - This study was designed to compare the clinical results of an ab externo approach
      to laser sclerostomy using two different laser sources under identical
      conditions. A pulsed (200 microseconds) erbium-YAG laser (lambda = 2940 nm) and a
      pulsed (200 microseconds) holmium:YAG laser (lambda = 2120 nm) were used. The
      energy of each laser was transmitted via a fiber (300 microns in diameter) and
      applied near the limbus, with the fiber tip remaining in steady contact with the
      sclera. According to the higher tissue absorption coefficient, a shorter
      penetration depth and, therefore, fewer complications were expected for the
      Er:YAG laser. A total of 26 patients with advanced open-angle glaucoma were
      treated and followed for up to 6 months. In all cases a functioning fistula with
      a prominent filtering bleb and a marked reduction in the intraocular pressure
      (from up to 35 mm Hg to < 10 mm Hg) could be achieved primarily. The total energy
      required was about 4 times lower for erbium:YAG laser was compared with
      holmium:YAG laser sclerostomies. No complication occurred intraoperatively.
      Postoperatively, reversible adherence of the iris to the internal ostium was more
      frequently observed in Ho:YAG laser sclerostomies (60%) and small hyphemas were
      more often seen in Er:YAG laser sclerostomies (30%). After 6 months of follow-up,
      about 40% of the fistula remained patent in both groups. In principle, both
      lasers are suited to serve as energy sources for the described approach. Under
      the conditions of the present study, different levels of thermal effects did not
      cause any significant difference in the clinical success rate.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7728104
TI  - Therapeutic range in transscleral contact cyclophotocoagulation.
AB  - Laser contact cyclophotocoagulation (CP) increasingly replaces noncontact CP and
      cryotherapy as it produces less damage to the conjunctiva and sclera. However,
      the optimal wavelength and protocol for treatment have not yet been firmly
      established. We used a contact continuous-wave (cw)-Nd:YAG laser at 1064 nm
      (Meridian-Microruptor III) with a bare fiber. A total of 30 freshly enucleated
      porcine eyes with brown irides were treated within 12 h of enucleation. The
      intraocular pressure was kept at 35-40 mmHg with an infusion system. The fiber
      was placed at a 1.5-mm distance from the limbus perpendicularly to the scleral
      surface, and applications were made using power levels ranging from 1.0 to 10.0 W
      for exposure periods of 0.5, 0.7, 1.0, 1.5, 2.0, 3.0, and 4.0 s. A just-visible
      whitening of the ciliary body was defined as a minimal effect, a complete
      whitening without loss of ciliary structures was defined as a medium effect, and
      a complete whitening with loss of ciliary structures was defined as a maximal
      effect. Supramaximal "pop" effects could be identified by the typical sound and
      the destruction of the ciliary body. Pop effects originate from a sudden
      overheating, which leads to the formation of small gas bubbles. Using an exposure
      duration of 0.5 s, no pop effect or maximal effect was observed. For longer
      exposure periods the therapeutic range decreased continuously (3.7 +/- 2.7 W for
      0.5 s, 0.3 +/- 0.3 W for 4.0 s).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728105
TI  - Cataract extraction combined with trabeculotomy.
AB  - Eyes with glaucomatous damage as well as eyes showing a clear elevation of
      intraocular pressure (IOP) to levels above normal frequently develop a permanent
      elevation of IOP after phacoemulsification or extracapsular cataract extraction,
      whereas the pressure in normal eyes usually decreases. In eyes with glaucomatous
      damage, we therefore combined cataract extraction with an antiglaucomatous
      operation, especially if a moderate pressure elevation was present: trabeculotomy
      and cataract extraction were performed in the same procedure. A corneal incision
      was used for phacoemulsification or extracapsular cataract extraction. The
      effects of the operation on the IOP and the visual acuity as well as the
      incidence of postoperative complications were investigated. In 44 operated eyes,
      the combination of cataract extraction and trabeculotomy proved to result in few
      complications and had a sufficient pressure-decreasing effect that continued
      throughout the 18 months of postoperative follow-up.

PMID- 7728106
TI  - Advanced primary open-angle glaucoma is associated with decreased ophthalmic
      artery blood-flow velocity.
AB  - Recent findings indicate that low-tension glaucoma is associated with impaired
      ocular blood flow. In the present study we evaluated the blood-flow in the
      ophthalmic artery in regulated open-angle glaucoma. Using pulsed Doppler
      sonography (4 MHz), the blood-flow velocity in the ophthalmic artery of 183 eyes
      of 95 persons with open-angle glaucoma was examined (mean age, 66.6 +/- 14.5
      years). The patients showed advanced glaucomatous optic-nerve atrophy (cup-to
      disk ratio, 0.74 +/- 0.27) and regulated intraocular pressure (IOP: range, 8-25
      mm Hg; mean, 16.4 +/- 3.9 mm Hg). The blood pressure (BP) was 140 +/- 22
      (systolic) and 79 +/- 14 mm Hg (diastolic). The control group (84 eyes of 44
      persons: mean age, 69.7 +/- 7.7 years; IOP range, 10-22 mm Hg; mean IOP, 15.2-2.6
      mm Hg; BP, 143 +/- 20/81 +/- 9 mmHg was matched for age and circulatory risk
      factors. The vascular resistance index (RIO) was calculated by the equation RIO =
      (systolic blood velocity-diastolic blood velocity)/systolic blood velocity. We
      found that the blood velocity in the ophthalmic artery was significantly
      decreased in glaucomatous eyes in contrast to normal eyes: systolic peak
      velocity, 36.9 +/- 16.2 cm/s (normal, 40.2 +/- 10.9 cm/s; P < 0.001); diastolic
      peak velocity 9.9 +/- 4.4 cm/s (normal, 11.7 +/- 4.0 cm/s, P < 0.0001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7728107
TI  - Vitreoretinal surgery in advanced Coat's disease.
AB  - Massive subretinal exudates as well as vitreal traction often induce complicated
      retinal detachments in patients with advanced Coats' disease. If left untreated,
      most patients experience secondary glaucoma by rubeosis and phthisis bulbi in
      addition to irreversible visual loss. We report on the surgical procedures used
      and results obtained in three patients aged between 21 and 28 years with combined
      exudative and traction-induced detachment. In all cases, extensive but
      unsuccessful retinal coagulation had been performed. The surgical intervention
      was done by application of an encircling buckle followed by vitrectomy and
      removal of preretinal membranes and subretinal lipid exudates via retinectomies.
      Particular attention was paid to the intensive endodiathermy of retinal
      teleangiectasies during surgery. Surgery was concluded by siliconeoil tamponade.
      Postoperatively, progressive resorption of remaining exudates and teleangiectatic
      vessels could be observed. All patients demonstrated stable functional and
      anatomic results at the last follow-up examination performed at 13 months to 6
      years after surgery. A stabilization of the anatomic and functional situation can
      be achieved even in advanced cases of Coats'-induced traction retinal detachment
      by vitreoretinal surgery.

PMID- 7728108
TI  - Vitreoretinal surgery in intermediate uveitis.
AB  - Between 1987 and 1992, vitrectomies were performed in 42 eyes with intermediate
      uveitis. Pre- and postoperative clinical and ophthalmological parameters were
      reviewed. Especially the pre- and postoperative time courses of visual acuity
      were analyzed. We looked for parameters influencing the final visual results.
      Furthermore, we revised pre- and postoperative recurrent exacerbations of the
      disease and the duration and dosage of postoperative corticosteroid therapy. The
      best final visual results were reached in eyes with the best preoperative visual
      acuities. Anatomic retinal findings and the preoperative duration of intermediate
      uveitis predominantly influenced the final visual results. Overall, 75% of our
      patients reached visual acuities of above 20/200. When asked to state their
      opinion about the final functional result, 80% of the patients were contented. We
      advocate vitrectomy in patients with intermediate uveitis after intensive follow
      up and careful consideration. The anatomic integrity of the retina, a good
      preoperative visual acuity, and a short preoperative duration of intermediate
      uveitis are the most important factors influencing the final visual results.

PMID- 7728109
TI  - Autosomal dominant exudative vitreoretinopathy: linkage analysis and its clinical
      application.
AB  - Close linkage without recombination (Zmax = 7.383 at Theta = 0.00) was found
      between the locus for autosomal dominant exudative vitreoretinopathy (Criswick
      Schepens) and the locus D11S388 in 11q14.3-q21. We report on the application of
      data from linkage studies in the diagnostic management of this disease. To
      determine the disease risk for two newborn children of two affected mothers more
      precisely, indirect genotype analysis was performed by typing their DNA for three
      DNA polymorphisms, the loci of which have been shown to be closely linked to the
      locus of autosomal dominant exudative vitreoretinopathy.

PMID- 7728110
TI  - Indicators of oxidative tissue damage and inflammatory activity in epiretinal
      membranes of proliferative diabetic retinopathy, proliferative vitreoretinopathy
      and macular pucker.
AB  - PURPOSE: To evaluate whether oxidative tissue damage and inflammatory reactions
      occur in epiretinal membranes of eyes suffering from proliferative diabetic
      retinopathy (PDR), proliferative vitreoretinopathy (PVR), and macular pucker
      (MP). METHODS: Epiretinal membranes were removed during surgery and frozen at -80
      degrees C (PDR, n = 26; PVR, n = 24; MP, n = 15), and oxidative tissue damage and
      inflammatory activity (MPO) of the membrane tissue were determined. The values
      are expressed as means of thiobarbituric acid-reactive substances (TBARS,
      nmol/mg) and MPO (units/mg). RESULTS: Both TBARS and MPO activity were
      significantly elevated (P < 0.05) in membranes of eyes suffering from PVR and PDR
      compared to MP. The myeloperoxidase activity in PDR membranes was significantly
      increased (P < 0.05) compared to PVR. CONCLUSIONS: Inflammatory cells and
      oxidative metabolites lead to oxidative reactions in PDR and PVR. The
      proliferation of membrane tissue may be enhanced through products of the
      lipoxygenase pathway, which is active in inflammatory cells and leads to
      oxidative tissue damage. Chemoattraction of leukocytes by oxidative metabolites
      renders the process self-progagating. Since patients suffering from MP have an
      intact vitreous body with an intact antioxidative system, this reaction occurs to
      a lesser degree, resulting in less membrane-growth activity. The cell-growth
      enhancing properties of inflammatory cells should be further investigated in PDR
      and PVR with regard to new therapeutic interventions.

PMID- 7728111
TI  - Centrally tinted contact lenses. A useful visual aid for patients with
      achromatopsia.
AB  - Achromatopsia (rod monochromacy) is a congenital color-vision defect of autosomal
      recessive inheritance due to severely abnormal or totally absent cone function.
      The disease is characterized by markedly reduced visual acuity, nystagmus, and,
      often, ametropia. Even under normal daylight conditions, these patients are
      extremely handicapped by glare because of a lack of rod inhibition by the
      abnormal or deficient cones. Light-absorbing glasses (absorption > 90%) can
      ameliorate this visual impairment to a certain extent but are sometimes not
      accepted by the patient since they are felt to disfigure the face. Especially
      during the first few years of school, this can lead to psychological problems. A
      special contact lens (Hydroflex, Wohlk Company, Kiel) with a centrally tinted
      area (absorption 80%) that is slightly greater in diameter than the pupil under
      daylight conditions can correct ametropia and reduce light exposure and dazzle in
      a cosmetically much better way. Our first experience with this kind of visual aid
      in a 9-year-old girl suffering from incomplete achromatopsia is presented.

PMID- 7728112
TI  - Can potentials from the visual cortex be elicited electrically despite severe
      retinal degeneration and a markedly reduced electroretinogram?
AB  - Outer retinal degenerations can cause severe visual handicap. Specific treatment
      is lacking. There is good histologic evidence that even in the face of total
      photoreceptor loss the ganglion cells remain viable. This study evaluates the
      possibility of eliciting an evoked potential by electrical stimulation of rabbit
      eyes with experimentally induced outer retinal degenerations. Electrical
      stimulation using a bipolar contact-lens electrode was performed in normal
      rabbits as well as in rabbits with experimentally induced outer retinal
      degenerations. Outer retinal degenerations were induced by injecting
      intravenously either monoiodoacetic acid (IAA) or sodium iodate (NaIO3). After
      administration of IAA or NaIO3, the electroretinogram was absent or markedly
      reduced and, histologically, the photoreceptor layer was severely damaged.
      However, the electrically evoked visual cortical response could nonetheless be
      elicited. We conclude that electrical stimulation of the globe can elicit evoked
      potentials from the visual cortex despite severe outer retinal damage. These
      results provide support for future efforts toward testing the feasibility of
      bypassing damaged outer retina and electrically stimulating the inner retina of
      patients with profound visual loss from retinitis pigmentosa.

PMID- 7728113
TI  - Granulomatous posterior uveitis in multiple sclerosis.

PMID- 7728114
TI  - Sclerostomy ab interno using long-wave laser modalities: acute morphological
      effects.
AB  - Sclerostomy fistulas were created ab interno in cadaver porcine eyes by an active
      contact method using a 200-microns-diameter silica optical fiber in conjunction
      with either Ho:YAG-, Nd:YAG-, or diode-laser light, and a qualitative comparison
      of the degree of collateral thermal damage induced in each case was undertaken at
      the light and electron microscopic levels. The apparent breadth of coagulated
      tissue observed in association with cross-sectioned fistula profiles exhibited
      considerable local variation, irrespective of the radiation source employed; no
      intrinsic difference in either the intensity or the extent of the thermal insult
      incurred was noted between the three laser modalities.

PMID- 7728115
TI  - Topological and phenomenological classification of bursting oscillations.
AB  - We describe a classification scheme for bursting oscillations which encompasses
      many of those found in the literature on bursting in excitable media. This is an
      extension of the scheme of Rinzel (in Mathematical Topics in Population Biology,
      Springer, Berlin, 1987), put in the context of a sequence of horizontal cuts
      through a two-parameter bifurcation diagram. We use this to describe the
      phenomenological character of different types of bursting, addressing the issue
      of how well the bursting can be characterized given the limited amount of
      information often available in experimental settings.

PMID- 7728116
TI  - Preparative regimens for patients with leukemias and severe aplastic anemia
      (overview): biological basis, experimental animal studies and clinical trials at
      the Fred Hutchinson Cancer Research Center.
AB  - Two purposes are served by conditioning regimens for allogeneic BMT. One is to
      suppress the patient's immune system so the foreign graft can take. The other
      purpose is to eliminate the underlying disease for which the patient is
      transplanted. This report reviews the recent developments in areas of
      conditioning programs for patients with aplastic anemia and hematological
      malignancies.

PMID- 7728117
TI  - Allogeneic Bone Marrow Transplantation, State of the Art and Future Directions.
      Symposium proceedings. Essen, Germany, October 13-14, 1993.

PMID- 7728118
TI  - Late effects after allogeneic bone marrow transplantation.

PMID- 7728119
TI  - Regimen-related acute toxicities: pathophysiology, risk factors, clinical
      evaluation and preventive strategies.

PMID- 7728120
TI  - The lung as a critical organ in marrow transplantation.
AB  - Respiratory failure is the main cause of death in patients undergoing bone marrow
      transplantation (BMT). In this paper, clinical and research aspects as well as
      diagnostic, prophylactic and therapeutic strategies concerning the various forms
      of pulmonary and bronchial complications, which may evolve after BMT, are
      discussed. Both cytomegalovirus (CMV)-induced interstitial pneumonia (PM) and the
      idiopathic pneumonia syndrome rarely occur in the cytopenic phase post-BMT.
      Haematological reconstitution with donor type cells seems to be a prerequisite to
      the development of these complications, suggesting a key role of immunological
      reactions. While CMV pneumonia can be effectively treated or prevented by
      ganciclovir, the idiopathic syndrome is usually fatal. Due to improved
      prophylaxis and therapy, lethal interstitial PM due to Pneumocystis carinii,
      herpes simplex, varizella zoster or Toxoplasma gondii as well as lethal PM caused
      by bacteria or Candida species are comparatively rare events. Aspergillus
      species, on the other hand, have emerged as frequent causative pathogens in
      lethal PM during the past years. Prolonged granulocytopenia and prolonged
      medication with corticosteroids are major risk factors of pulmonary
      aspergillosis, which is usually fatal; effective prophylaxis may be achieved by
      sterile air supply during the hospital stay and by inhalation of amphotericin B
      thereafter. Pulmonary haemorrhage, as diagnosed by bronchoalveolar lavage (BAL),
      may develop due to the toxicity of the conditioning regimen, or may be secondary
      to infectious PM of various kind. Congestive heart failure or the application of
      cytokines might give rise to the development of pulmonary oedema. Patients with
      hepatic veno-occlusive disease have a high risk of subsequent pulmonary
      complications, possibly on the basis of toxic lung injury. Venous thromboembolism
      or air embolism may occur; they are usually venous catheter-associated. Pleural
      effusions may develop secondary to infection, congestive heart failure, veno
      occlusive disease, pulmonary embolism or malignancy. Patients with bronchiolitis
      obliterans, which leads to progressive respiratory failure, present with an
      obstructive pattern in lung function tests and hyperinflated lungs on chest
      radiographs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7728121
TI  - Functional ability and quality of life of patients after allogeneic bone marrow
      transplantation.
AB  - In recent years, increasing attention has focused on the quality of life of long
      term survivors of bone marrow transplantation. Most survivors appear to have good
      health and high levels of functional capacity, exhibit little psychological
      distress and achieve social adaptation and resumption of valued roles. In
      addition, they conduct educational and employment pursuits and experience
      satisfaction with their lives at levels comparable to the general population.
      However, some survivors, especially those with chronic graft-versus-host disease,
      report low levels of these parameters. Challenges for future studies are to
      identify the various changes that occur over time, the tempo at which they occur,
      how the changes interact, and what parameters predict for positive and adverse
      outcomes. Such investigations will provide the basis of strategies to optimize
      good outcomes.

PMID- 7728122
TI  - Immunogenetic marrow donor search for 1012 patients: a retrospective analysis of
      strategies, outcome and costs.
AB  - To analyse strategies, outcome and costs of immunogenetic marrow donor search
      1012 patients were enrolled in a retrospective single centre study covering the
      period from January 1990 to December 1992. An HLA-compatible donor was identified
      for 562 of the patients (55.4%). Core family donor search (CFDS) provided a donor
      for 39%, extended family donor search (EFDS) for 6.4% and unrelated marrow donor
      search (UMDS) for 10% of the patients. During the period analysed, UMDS success
      rate increased from 13.3% to 47.8%, while mean search length decreased from 7.2
      to 4.8 months. The percentage of donors from German registries rose from 5% in
      1990 to 50% in 1993. Search length was dependent on patient's HLA phenotype
      frequency, but even for patients with frequencies as low as < 1:3 000 000 a donor
      was found in 5 of 24 cases. The mean costs (DM) per donor identified by CFDS,
      EFDS and UMDS were 2921, 19 172 and 24 036, respectively. Thus, CFDS is the
      utmost effective type of search. In view of the clinical outcome of BMT, EFDS
      remains a meaningful strategy and should not be replaced by UMDS despite its
      increasing success rate.

PMID- 7728123
TI  - Marrow transplantation using volunteer unrelated donors in a comparison of
      mismatched family donor transplants: a Seattle perspective.
AB  - Although allogeneic marrow transplantation has evolved into the treatment of
      choice for many otherwise fatal diseases, most patients are not candidates as
      they do not have an HLA-matched sibling donor. The Seattle Marrow Transplant
      Team, among others, has shown that patients who receive grafts from relatives who
      are partially matched for HLA (5 of 6 HLA-A,-B,-DR antigens) have an increased
      risk of graft-versus-host disease, but an overall survival that is comparable to
      that of similar patients receiving grafts from HLA-matched siblings. Similarly,
      patients receiving grafts from HLA-matched unrelated donors are at high risk for
      GVHD, but can look forward to favorable outcomes nearly as frequently as those
      who receive grafts from matched relatives. Grafts from more HLA-disparate donors,
      either related or unrelated, are at substantially increased risk of complications
      and death.

PMID- 7728124
TI  - Radiobiology of total body radiation.
AB  - The first bone marrow transplants (BMTs) in human patients were performed after
      conditioning with total body irradiation (TBI). TBI remains an important part of
      BMT protocols. The morbidity and mortality of BMT remains significant, but can be
      decreased by the introduction of optimized TBI regimens. This requires dosimetric
      control and a detailed analysis and description of the physics of the TBI
      procedure in every BMT center that utilizes TBI. Recommendations for such
      procedures are given. Radiobiological models are of help in developing less toxic
      TBI procedures, but can only be effective after dosimetric control has been
      obtained and if the influence of other variables on the outcome of BMT are taken
      into account. Fractionated TBI (fraction size over 3.0 Gy or higher) appears to
      be more effective and better tolerated than single fraction TBI. Lung shielding
      is possible during TBI. Smaller organs or organs that cannot be imaged easily are
      not recommended for shielding. Radiolabeled immunoglobulins are but low molecular
      weight bone seeking radioisotopes and are not expected to improve the therapeutic
      ratio of TBI. Other variables in BMT are more difficult to quantify and model
      than TBI (e.g. high-dose chemotherapy, graft-versus-host disease) and will be
      more difficult to optimize.

PMID- 7728125
TI  - Molecular techniques for typing unrelated marrow donors: potential impact of
      molecular typing disparity on donor selection.
AB  - HLA matching between a bone marrow recipient and donor is one of the major
      factors influencing transplant success. However, it is not possible to locate an
      HLA-identical donor for about 70% of patients who might benefit from bone marrow
      transplantation (BMT). New molecular biological methods for detection of HLA
      polymorphism currently provide an opportunity to improve HLA matching of
      unrelated donors as well as a research tool to investigate the relationship
      between HLA disparity and transplant complications. These molecular HLA typing
      methods include sequence-specific amplification, hybridization with
      oligonucleotide probes, heteroduplex formation and direct nucleotide sequencing.
      Molecular HLA typing is being utilized to address questions regarding the extent
      of HLA disparity between two unrelated individuals and the effect of HLA
      disparity that is not detected using conventional HLA typing methods.
      Accumulating data suggest some HLA disparities may be tolerated while others are
      very immunogenic. Use of more precise HLA typing may contribute to the success of
      future transplants utilizing alternative donors. A better understanding of the
      relationship between HLA disparity and transplant complications may make it
      possible to relax the stringency of donor matching to make BMT available to
      larger numbers of patients.

PMID- 7728126
TI  - Biology of acute and chronic graft-versus-host reactions: predictive value of
      studies in experimental animals.
AB  - Experimental research on graft-versus-host disease (GVHD) with laboratory animals
      has been performed mainly with rodents, rhesus monkeys and dogs. The basic
      immunological mechanisms operative in GVHD are largely similar in these three
      species and in human patients, although the patterns of GVHD in the three animal
      species show differences. The predictive value for clinical GVHD of the results
      obtained in the different animals species is analysed for the three main
      variables: namely, histocompatibility, T cell numbers in the graft and the
      intestinal microflora. Rhesus monkeys score highest as regards clinical relevance
      for the first two variables. With regards to the unravelling of detailed
      mechanisms of the influence of the microflora, none of the three animal species
      is likely to provide the information needed for identification of the bacterial
      species involved in the induction of GVHD in human patients.

PMID- 7728127
TI  - Prophylaxis and treatment of acute graft-versus-host disease: current state,
      implications of new immunopharmacologic compounds and future strategies to
      prevent and treat acute GVHD in high-risk patients.
AB  - Acute GVHD continues to be a clinical problem, particularly after transplants
      from HLA-non-identical donors. Standard prophylaxis at the present time involves
      the use of MTX and CYA with or without the addition of glucocorticoids. The use
      of moAbs, in particular humanized forms such as HAT, may improve these results. A
      selective manipulation of cytokines (IL-1, tumor necrosis factor and others) or
      their receptors or both may be clinically useful. The current use of a broad
      variety of approaches is a clear indication that the optimum treatment has been
      elusive.

PMID- 7728128
TI  - New approaches to the prophylaxis and treatment of bacterial and fungal
      infections in allogeneic marrow transplant recipients.
AB  - Bacterial and fungal infections continue to be a major threat to bone marrow
      transplant recipients. While standardized approaches to empiric therapy with
      early inclusion of antibiotics active against Gram-positive organisms and against
      fungi may have improved the outcome of these patients during the past decade,
      other developments (e.g. increasing number of patients in older age groups,
      unrelated donors, mismatch transplants) may even have increased the problem.
      Current approaches to the prophylaxis and treatment of these infections are
      discussed. Concerning fungal infections especially the new azoles and new
      approaches of amphotericin B administration are of interest.

PMID- 7728129
TI  - Early detection and treatment of cytomegalovirus infections in marrow transplant
      patients: methodological aspects and implications for therapeutic interventions.
AB  - Major advances have been made in the early detection of CMV infection after
      marrow transplant by the introduction of the polymerase chain reaction (PCR) and
      the CMV antigenemia assay. Numerous studies have established clinical
      correlations of these techniques but there is a need for technical
      standardization as assay sensitivity may vary considerably with different
      modifications. Current prevention strategies for CMV disease after marrow
      transplantation, including options on how the antigenemia assay and PCR assays
      may be used in early treatment strategies, are discussed.

PMID- 7728130
TI  - Role of marrow microenvironment in engraftment and maintenance of allogeneic
      hematopoietic stem cells.
AB  - Following allogeneic marrow transplantation a competent marrow microenvironment
      consists of a complex mixture of both donor and host derived cells. Clearly some
      forms of genetic disparity between donor and host can compromise appropriate
      interactions and function of these cells. The competency of the microenvironment
      can also be compromised by viral infections, and the underlying disease process
      as in rare cases of aplastic anemia. As we come to precisely define each
      component of the microenvironment, it will become possible to accurately diagnose
      causes of poor marrow function and develop methods for prevention and treatment.

PMID- 7728131
TI  - Hematopoietic growth factors after allogeneic marrow transplantation in animal
      studies and clinical trials.
AB  - The use of hematopoietic growth factors after allogeneic bone marrow
      transplantation (BMT) was investigated either in a preclinical canine model or in
      patients. G-CSF administration in dogs after high-dose total body irradiation
      (TBI) and transplantation of DLA-identical littermate marrow significantly
      accelerated recovery of peripheral blood neutrophils, monocytes and lymphocytes,
      but not of platelet counts, without significantly increasing the risks of graft
      failure or graft-versus-host disease (GVHD). GM-CSF given to patients after HLA
      identical sibling BMT was well tolerated at doses < or = 250 micrograms/m2/day
      and resulted in significantly faster neutrophil recovery compared with matched
      historical controls. Risks of graft failure, GVHD or relapse were not increased.
      When GM-CSF was given after matched or 1-antigen mismatched unrelated BMTs, the
      number of febrile days and septic episodes within the first 28 days was reduced
      even though neutrophil recovery was not accelerated. Incidences of graft failure,
      GVHD or relapse were not increased. In recipients of BMT with invasive fungal
      infections, M-CSF in combination with conventional anti-fungal therapy may have a
      beneficial effect on survival. Treatment with GM-CSF in patients with graft
      failure appears to result in improved survival without increasing the risks of
      GVHD or relapse.

PMID- 7728132
TI  - Selective reconstitution of CD8+ cytotoxic T lymphocyte responses in
      immunodeficient bone marrow transplant recipients by the adoptive transfer of T
      cell clones.
AB  - The adoptive transfer of T cells specific for antigens encoded by pathogens and
      tumors has been an effective treatment for infections and malignancies in animal
      models and is potentially applicable for infections occurring in immunodeficient
      bone marrow transplant recipients. This article reviews recent insights derived
      from studies of the immunobiology of human cytomegalovirus (CMV) infection in
      healthy and immunodeficient hosts and the development of adoptive immunotherapy
      as prophylaxis for CMV infection in recipients of allogeneic bone marrow
      transplants.

PMID- 7728133
TI  - Role of etoposide (VP-16) in preparatory regimens for patients with leukemia or
      lymphoma undergoing allogeneic bone marrow transplantation.
AB  - In 1983, we began a series of clinical trials with the goal of reducing the
      relapse rate following allogeneic BMT for hematologic malignancies. Because of
      its anti-leukemic activity, the drug VP-16 was chosen and combined with total
      body irradiation (TBI). The first series (trial I) consisted of patients who had
      advanced leukemia. This trial showed a relapse rate of 32% and a disease-free
      survival rate of 43%. Thereafter, this regimen was tested in a randomized trial
      (trial II) under the auspices of the Southwest Oncology Group (SWOG study 8612).
      The FTBI/VP-16 regimen was compared with the combination of busulfan and
      cyclophosphamide (BU/CY). A recent analysis indicates a disease-free advantage
      for patients prepared with FTBI/VP-16; however this difference is not
      statistically significant. In another trial (trial III), patients in their first
      remission of leukemia were prepared with the FTBI/VP-16 regimen and long-term
      disease-free survival was found to be 60-70% with a relapse rate of approximately
      10%. These results compare favorably with data obtained with alternative
      preparatory regimens. The FTBI/VP-16 regimen is currently being compared to the
      'standard' regimen, FTBI/CY, in a prospective trial (trial IV). Since the regimen
      related toxicity has been relatively low, we have added one dose of CY 60 mg/kg
      to the FTBI/VP-16 combination. This regimen (trial V) is currently being tested
      in patients with advanced leukemia. The preliminary results of this ongoing trial
      indicate further improvement in disease-free survival through a reduction of the
      post-transplant relapse rate.

PMID- 7728134
TI  - Research utilization improves nursing practice.

PMID- 7728135
TI  - The assessment of plutonium and americium in contaminated wounds with high energy
      resolution semiconductor detectors.
AB  - A simple to use method was installed for the measurement of wounds contaminated
      with plutonium and americium by using a semiconductor detector. This technique
      does not explicitly require the knowledge of the detector efficiency but uses a
      plant 241Am calibration source. A computer programme has also been developed for
      the quantification of the contamination according to the shape and the depth of
      the contaminant in the wound.

PMID- 7728136
TI  - The large, free-living amoebae: wonderful cells for biological studies.
AB  - The large, free-living amoebae have been widely used as model cells for studying
      a variety of biological phenomena, including cell motility, nucleocytoplasmic
      interactions, membrane function, and symbiosis. Results of studies by our group
      on amoebae as moving cells, as material for micrurgical manipulations, and as
      hosts for intracellular symbionts are summarized here. In particular, our recent
      studies of the amoeba as a microcosm, in which spontaneously infecting foreign
      microbes have become integrated as necessary cell components, are described in
      some detail. These processes have involved an initial microbial infection, mutual
      adaptation by the host and symbionts, and development of obligatory symbiosis.
      Evidence is presented to show that symbiont-derived macromolecules are involved
      in the protection of symbionts from digestion, the symbionts have acquired
      regulatory elements on their chromosomal genes to enhance production of
      beneficial gene products, and symbionts apparently utilize host-derived
      macromolecules to their benefit. These studies involved morphological
      observations both at light and electron microscopic levels, physiological and
      genetic studies, production and use of poly- and monoclonal antibodies, and
      molecular-biological approaches including gene cloning and sequencing. It is
      shown that amoebae are uniquely suited as model cells with which to study these
      phenomena.

PMID- 7728137
TI  - Transcription factor genes from rat Pneumocystis carinii.
AB  - Genes encoding the TFIID TATA-box binding protein (TBP) from two probable species
      of rat Pneumocystis carinii (prototype and variant) were sequenced. The two P.
      carinii TBP gene sequences were 91% identical to each other, and 65-77% identical
      to TBP genes from other species. A cDNA from one of the two P. carinii TBP genes
      was sequenced, which showed that four small introns resided in identical
      positions within the TBP genes from the prototype and variant rat P. carinii.
      Conservation of the 180 amino acids that constitute the conserved core of TBP was
      97% between the P. carinii TBP, which were 95% and 97% identical to conserved
      core sequences of TBP from Saccharomyces cerevisiae and Schizosaccharomyces pombe
      respectively.

PMID- 7728138
TI  - Polymorphism of the thymidylate synthase gene of Pneumocystis carinii from
      different host species.
AB  - Pneumocystis carinii is an opportunistic agent found in the lung of various
      mammals which often causes severe pneumonia in immunocompromised humans,
      especially in AIDS patients. In the past several years significant additions have
      been made to the collection of knowledge we have concerning the genetic diversity
      of P. carinii. These additions provide new understanding of Pneumocystis
      transmission and the effect of possible reservoirs of Pneumocystis in the various
      species. In this study, a 400-bp fragment of the thymidylate synthase (TS) gene
      of P. carinii has been amplified by PCR from 43 parasite isolates obtained from 4
      mammalian host species: rat, mouse, rabbit and human. A probe selected from the
      TS gene sequence of rat-derived P. carinii was hybridized with the amplified
      products from rat- and mouse-derived P. carinii, but not with rabbit or human P.
      carinii DNA. Restriction profiles were performed on amplified fragments from all
      isolates, and the 4 nucleotide sequences of the TS gene fragment amplified from
      rat, mouse, rabbit and human P. carinii were determined. Differences were
      detected in the gene fragment in P. carinii isolates from the 4 host species;
      however no difference was revealed in P. carinii isolates within a single host
      species, whatever the host strain or its geographic origin. Thus, the sequence
      differences of the P. carinii TS gene appeared as host-species specific. A
      specific probe which recognized all human P. carinii isolates was defined.

PMID- 7728139
TI  - Comparison of coding and spacer region sequences of chromosomal rRNA-coding genes
      of two sequevars of Pneumocystis carinii.
AB  - Two distinct sequevars, denoted Pc1 and Pc2, of the opportunistic pathogen
      Pneumocystis carinii have been previously identified based on the sequence of
      their 26S rRNA genes, the location of group I self-splicing introns and pulsed
      field electrophoretic patterns of chromosomal DNA. This study shows that the
      sequences of 16S and 5.8S rRNA genes also vary between these sequevars, and that
      greater variation was seen in the internal transcribed spacer regions. Polymerase
      chain reaction and restriction analysis can distinguish between these sequevars.

PMID- 7728140
TI  - Effect and localization of trifluralin in Plasmodium falciparum gametocytes: an
      electron microscopic study.
AB  - Trifluralin, a herbicide which is known to bind to plant and algal tubulin,
      induced ultrastructural changes in the microtubules of the mature Plasmodium
      falciparum gametocytes in vitro. Trifluralin treatment led to disassembly of the
      well ordered subpellicular microtubules, whereas it had no effect on microtubules
      of human platelets or of rat neuronal cells in vitro. The disassembled
      microtubules showed fragmented large tubular structures, which frequently were
      associated with the pellicular membranes. Electron microscopic autoradiography
      showed radioactive trifluralin associated with the microtubule fragments. These
      results provide evidence that trifluralin selectively binds to microtubules in
      malaria parasites and causes disruption of their structure.

PMID- 7728141
TI  - Molecular evolutionary analyses of nuclear-encoded small subunit ribosomal RNA
      identify an independent rhizopod lineage containing the Euglyphina and the
      Chlorarachniophyta.
AB  - The Rhizopoda comprise a diverse assemblage of protists which depend on lobose or
      filose pseudopodia for locomotion. The biochemical and morphological diversity of
      rhizopods has led to an uncertain taxonomy. Ribosomal RNA sequence comparisons
      offer a measure of evolutionary relatedness that is independent of morphology and
      has been used to demonstrate a polyphyletic origin of the Lobosea. We sequenced
      complete small subunit ribosomal RNA coding regions from the filose amoebae,
      Euglypha rotunda and Paulinella chromatophora (Euglyphina) to position these taxa
      in the eukaryote phylogeny. The neighbor-joining analyses show that E. rotunda
      and P. chromatophora share a monophyletic origin and are not closely related to
      any lobose amoebae in our analyses. Instead, the Euglyphina form a robust sister
      group to the Chlorarachniophyta. These results provide further evidence for the
      polyphyly of the Rhizopoda and support the creation of a new amoeboid lineage
      which includes the Euglyphina and the chlorarachniophyte algae; taxa with tubular
      mitochondrial cristae and filose or reticulate pseudopodia.

PMID- 7728142
TI  - Isotricha jalaludinii n. sp. found from the rumen of lesser mouse deer, Tragulus
      javanicus, in Malaysia.
AB  - Isotricha jalaludinii n. sp. found in the rumen of lesser mouse deer, Tragulus
      javanicus, in Malaysia was described and illustrated. This new species is
      characterized by the location and direction of the vestibulum, shape of the
      macronucleus, and absence of a dent at the vestibular opening. The presence of
      single peculiar isotrichid species in the rumen of mouse deer, which is
      recognized as one of the most primitive ruminants, suggests that the isotrichid
      ciliates similar to I. jalaludinii and Isotricha intestinalis were established at
      a fairly early period during the evolution of ruminants.

PMID- 7728143
TI  - Induction of antibiotic resistance in Paramecium tetraurelia by the bacterial
      gene APH-3'-II.
AB  - We have generated a transformation marker for Paramecium using a Paramecium
      expression vector (pPXV) and the open reading frame (ORF) of the bacterial
      antibiotic resistance gene aminoglycoside 3'-phosphotransferase-II (APH-3'-II or
      neor) from the transposon Tn5. The expression vector contained a small multiple
      cloning site between the 5' and 3' non-coding regions of the calmodulin gene, and
      Tetrahymena telomere sequences for the stability of the plasmid in Paramecium.
      After the neor ORF was inserted, the plasmid was referred to as pPXV-NEO.
      Delivery of approximately 10-20 picoliters of linearized PXV-NEO at > or = 2000
      copies/pl into the macronucleus effected 100% transformation. Southern and
      Northern blot hybridization showed the presence of neor-specific DNA and RNA,
      respectively, in all of the transformed clones but not in the untransformed
      clones. The degree of resistance to G-418, and the concentrations of neor
      specific DNA and neor-specific RNA in the clones were proportional to the
      concentration of the vector injected. We have demonstrated that when the
      linearized plasmid was injected into the macronucleus, the prokaryotic sequence
      conferred an antibiotic resistance to Paramecium despite codon-usage differences.

PMID- 7728144
TI  - Phylogenetic relationships among anuran trypanosomes as revealed by riboprinting.
AB  - Twenty trypanosome isolates from Anura (frogs and toads) assigned to several
      species were characterized by riboprinting-restriction enzyme digestion of
      polymerase chain reaction amplified small subunit ribosomal RNA genes.
      Restriction site polymorphisms allowed distinction of all the recognized species
      and no intraspecific variation in riboprint patterns was detected. Phylogenetic
      reconstruction using parsimony and distance estimates based on restriction
      fragment comigration showed Trypanosoma chattoni to be only distantly related to
      the other species, while T. ranarum and T. fallisi appear to be sister taxa
      despite showing non-overlapping host specificities.

PMID- 7728145
TI  - Molecular etiology of factor VIII deficiency in hemophilia A.
AB  - Hemophilia is a common X-linked coagulation disorder due to deficiency of factor
      VIII. The factor VIII gene has been cloned in 1984 and a large number of
      mutations that cause hemophilia A have been identified in the last decade. The
      most common of the mutations is an inversion of factor VIII that accounts for
      nearly 45% of patients with severe hemophilia A. This review lists all the factor
      VIII mutations identified to date and briefly discusses their functional
      significance.

PMID- 7728146
TI  - Absence of mutations in the apolipoprotein E (APOE) gene of patients with
      Alzheimer disease.

PMID- 7728147
TI  - Rapid nonradioactive assay for the detection of the common French Canadian
      tyrosinemia type I mutation.

PMID- 7728148
TI  - Molecular, biochemical, and clinical characterization of mitochondrial
      acetoacetyl-coenzyme A thiolase deficiency in two further patients.
AB  - The molecular basis of mitochondrial acetoacetyl-CoA thiolase (T2) deficiency was
      studied in two patients (GK11 and GK16). Fibroblasts from each patient had
      detectable immunoreactive T2 polypeptide (CRM). In pulse-chase experiments,
      fibroblasts from GK11 had two types of CRM: one (type I CRM) disappeared after a
      24-hr chase and migrated more slowly than that of the normal control; the other
      (type II CRM) was detected with a small amount even after a 72-hr chase and had
      normal electrophoretic mobility. GK16's fibroblasts had a CRM (type III) which
      was also detectable even after a 72-hr chase and showed a slower mobility than
      type I CRM. By analyzing amplified cDNA and genomic fragments, we showed that
      both patients are genetic compounds; GK11 for the mutations N158D and T297M, and
      GK16 for the mutations A301P and IVS8 (+1). Expression analyses confirmed that
      mutant T2 subunits with N158D, T297M, and A301P correspond to type I, II, and III
      CRM, respectively. Among them, only the mutant T2 polypeptide with T297M appeared
      to have a detectable residual activity, in spite of its instability.
      Cotransfection of two cDNAs containing N158D and T297M suggested that
      heterotetramer formation reduces residual activity in GK11 cells.

PMID- 7728149
TI  - Somatic spectrum of cancer-associated single basepair substitutions in the TP53
      gene is determined mainly by endogenous mechanisms of mutation and by selection.
AB  - The spectrum of somatic TP53 single basepair substitutions detected in 955
      cancers was compared with that of 2,224 different germline mutations in 279
      different human genes (other than TP53), reported as the cause of inherited
      disease. This comparison reveals that, disregarding a relatively small subset
      (12%) of TP53 mutations that probably result from the action of exogenous
      mutagens, both the relative rates and the nearest-neighbor spectra of single
      basepair substitutions are similar in the two datasets. This spectral resemblance
      suggests that a substantial proportion of cancer-associated somatic TP53
      mutations result from endogenous cellular mechanisms. The likelihood of clinical
      observation of a particular mutation type differs, however, between tumors and
      genetic diseases, when the chemical properties of the resulting amino acid
      substitutions are considered. Together with a sixfold higher observation
      likelihood for mutations at evolutionarily conserved residues, this finding
      argues that selection is a critical factor in determining which TP53 mutations
      are found to be associated with human cancer.

PMID- 7728150
TI  - Apolipoprotein A-IV polymorphism in the Hungarian population: gene frequencies,
      effect on lipid levels, and sequence of two new variants.
AB  - The genetic polymorphism of human apolipoprotein A-IV was investigated in
      Hungarian blood donors (n = 202) by isoelectric focusing (IEF) of plasma samples
      followed by immunoblotting. The frequency of apo A-IV alleles was f(A-IV1) =
      0.95, f(A-IV2) = 0.039 and f(A-IV3) = 0.002. This frequency distribution is
      significantly different from other Caucasian populations (P < 0.05). The
      association of apo A-IV phenotypes with HDL-cholesterol concentration which was
      previously described for two other European populations was only of borderline
      significance (P = 0.08). Three previously undescribed apo A-IV variants,
      designated Budapest-1, Budapest-2 and Budapest-3, were detected by IEF. The
      mutant proteins are not associated with alterations in the lipid/lipoprotein
      concentrations in heterozygotes. DNA-sequencing revealed two point mutations
      (Arg285-->Cys and Thr347-->Ser) in exon 3 of apo A-IV-Budapest-1 and a Glu-->Lys
      substitution at position 24 in exon 2 of apo A-IV-Budapest-2.

PMID- 7728151
TI  - Germline mutations in the von Hippel-Lindau disease tumor suppressor gene:
      correlations with phenotype.
AB  - von Hippel-Lindau disease (VHL) is an inherited neoplastic disease characterized
      by a predisposition to develop retinal angiomas, central nervous system
      hemangioblastomas, renal cell carcinomas, pancreatic cysts, and
      pheochromocytomas. The VHL gene was recently isolated by positional cloning. The
      cDNA encodes 852 nucleotides in 3 exons. The VHL gene is unrelated to any known
      gene families. We identified germline mutations in 85/114 (75%) of VHL families.
      Clinical heterogeneity is a well-known feature of VHL. VHL families were
      classified into 2 types based on the presence or absence of pheochromocytoma. The
      types of mutations responsible for VHL without pheochromocytoma (VHL type 1)
      differed from those responsible for VHL with pheochromocytoma (VHL type 2). Fifty
      six % of the mutations responsible for VHL type 1 were microdeletions/insertions,
      nonsense mutations, or deletions; 96% of the mutations responsible for VHL type 2
      were missense mutations. Specific mutations in codon 238 accounted for 43% of the
      mutations responsible for VHL type 2. The mutations identified in these families
      will be useful in presymptomatic diagnosis. The identification of mutations
      associated with phenotypes contributes to the understanding of fundamental
      genetic mechanisms of VHL disease.

PMID- 7728152
TI  - Dejerine-Sottas neuropathy is associated with a de novo PMP22 mutation.
AB  - We identified a de novo mutation in the peripheral myelin protein (PMP22) gene of
      a patient with Dejerine-Sottas neuropathy. Single-stranded conformation analysis
      of PCR-amplified DNA fragments showed an additional fragment for exon 1 in the
      patient, which was absent in the unaffected parents. Sequence analysis showed a
      de novo point mutation C85-->A that results in an amino acid substitution
      His12Gln in the first transmembrane domain of PMP22. This provides further
      evidence that sporadic cases of Dejerine-Sottas neuropathy can be due to dominant
      single base substitutions.

PMID- 7728153
TI  - Methods for rapid detection of a recurrent nonsense mutation and documentation of
      phenotypic features in neurofibromatosis type 1 patients.
AB  - We have developed a rapid screening method to detect a recurrent mutation in the
      neurofibromatosis type 1 gene. Using gene amplification and hybridization with
      allele-specific oligonucleotides, we screened 97 unrelated affected individuals
      for the recurrent C-->T substitution in codon 1947. The mutation was detected in
      1 patient and found to cosegregate with the disease phenotype in the patient's
      family. Although the estimated prevalence of this mutation is low, rapid
      screening of different patient cohorts would identify multiple individuals
      carrying the same mutation. Such data would provide the first opportunity for
      examining correlations between phenotypic characteristics and molecular genotype
      and would allow clinicians to offer early diagnosis and prenatal screening to
      affected families. A format for the comparison of phenotypic features in other
      settings is presented.

PMID- 7728154
TI  - Deletion detection in the dystrophin gene by multiplex gap ligase chain reaction
      and immunochromatographic strip technology.
AB  - The purpose of this study is to demonstrate the value of a multiplex
      amplification and readout system. The validation was done using as a model system
      the detection of deletions in nine possible dystrophin exons: 4, 8, 12, 17, 19,
      44, 45, 48, and 51. The amplification system was gap ligase chain reaction,
      adapted to amplify selected regions of multiple exons simultaneously. The
      amplified products were read out with an immunochromatographic methodology,
      adapted from that used in the Abbott product line commercialized under the name
      Test Pack Plus. In each amplification, the beta-globin gene was incorporated and
      served as a procedural control. The complete process takes < 3 hr from DNA sample
      to result. The procedure is therefore rapid and simple, as well as being
      potentially very cost effective. The combination of these two technologies is
      shown to be a useful tool for the determination of deletions in the nine exons of
      the dystrophin gene. The results of a 100-patient sample study showed concordance
      with cDNA and PCR in current use. Equivalent performance at two sites was shown.

PMID- 7728155
TI  - Mitochondrial acetoacetyl-coenzyme A thiolase gene: a novel 68-bp deletion
      involving 3' splice site of intron 7, causing exon 8 skipping in a Caucasian
      patient with beta-ketothiolase deficiency.

PMID- 7728156
TI  - Mutations of the iduronate-2-sulfatase gene in 12 Polish patients with
      mucopolysaccharidosis type II (Hunter syndrome).

PMID- 7728158
TI  - FBI: health care fraud the crime of choice.

PMID- 7728157
TI  - Effect of corticosteroids for fetal maturation on perinatal outcomes.
AB  - The National Institutes of Health Consensus Development Conference on the Effect
      of Corticosteroids for Fetal Maturation on Perinatal Outcomes brought together
      specialists in obstetrics, neonatology, pharmacology, epidemiology, and nursing;
      basic scientists in physiology and cellular biology; and the public to address
      the following questions: (1) For what conditions and purposes are antenatal
      corticosteroids used, and what is the scientific basis for that use? (2) What are
      the short-term and long-term benefits of antenatal corticosteroid treatment? (3)
      What are the short-term and long-term adverse effects for the infant and mother?
      (4) What is the influence of the type of corticosteroid, dosage, timing and
      circumstances of administration, and associated therapy on treatment outcome? (5)
      What are the economic consequences of this treatment? (6) What are the
      recommendations for use of antenatal corticosteroids? and (7) What research is
      needed to guide clinical care? Following 1 1/2 days of presentations by experts
      and discussion by the audience, a consensus panel weighed the evidence and
      prepared their consensus statement. The consensus panel concluded that antenatal
      corticosteroid therapy for fetal maturation reduces mortality, respiratory
      distress syndrome, and intraventricular hemorrhage in preterm infants. These
      benefits extend to a broad range of gestational ages (24-34 weeks) and are not
      limited by gender or race. Although the beneficial effects of corticosteroids are
      greatest more than 24 hours after beginning treatment, treatment less than 24
      hours in duration may also improve outcomes. The benefits of antenatal
      corticosteroids are additive to those derived from surfactant therapy. In the
      presence of preterm premature rupture of the membranes, antenatal corticosteroid
      therapy reduces the frequency of respiratory distress syndrome, intraventricular
      hemorrhage, and neonatal death, although to a lesser extent than with intact
      membranes. Whether this therapy increases either neonatal or maternal infection
      is unclear. However, the risk of intraventricular hemorrhage and death from
      prematurity is greater than the risk from infection. Data from trials with
      followup of children up to 12 years indicate that antenatal corticosteroid
      therapy does not adversely affect physical growth or psychomotor development.
      Antenatal corticosteroid therapy is indicated for women at risk of premature
      delivery with few exceptions and will result in a substantial decrease in
      neonatal morbidity and mortality, as well as substantial savings in health care
      costs. The use of antenatal corticosteroids for fetal maturation is a rare
      example of a technology that yields substantial cost savings in addition to
      improving health.

PMID- 7728159
TI  - Managed care ... consumers enrolled in HMOs are more satisfied.

PMID- 7728160
TI  - A patient's home (care) is his castle.

PMID- 7728161
TI  - 25,000 nurses make historic march on Washington.

PMID- 7728162
TI  - Health care's new heavyweights.
AB  - Fresh from delivering the knockout punch to federal health care reform
      legislation, employers have become the new power brokers in health care. Across
      the country, they're forcing unprecedented changes in payment and delivery, both
      individually and through business coalitions. If you're wondering what these new
      players are looking for, start by asking Helen Darling, who's blazing new trails
      at Xerox Corp.

PMID- 7728163
TI  - Don't fence us in. The Marshfield Clinic ruling may be bad news for integrated
      delivery.

PMID- 7728164
TI  - The trouble with CHINS (community health information networks).
AB  - If one had to choose a single acronym that captures both the vision and folly of
      today's health care industry, it would be "CHIN." The term--which stands for
      "community health information network"--combines the idealism of community-based
      health care with the promise of computer automation. Ironically, the acronym may
      come to be synonymous with "sticking your neck out"; these costly computer
      networks presuppose a quixotic collaboration among hospitals and health systems
      long at one another's competitive throats. For CHINs to succeed, they must
      overcome barriers that many industry insiders say are insurmountable.

PMID- 7728165
TI  - Houston. Texas-sized restructuring in a New York minute.

PMID- 7728166
TI  - Profiles in service (1986-1995). The Foster G. McGaw Prize winners. Greater
      Southeast Healthcare System, Washington, DC.
AB  - Greater Southeast Healthcare System, the 1989 award winner, isn't sitting by and
      letting Washington, DC's economic problems get the better of it. The system is
      moving forward to control costs, enhance its bottom line--and improve the health
      and socioeconomic status of its community. CEO Dalton Tong talks about the many
      challenges ahead.

PMID- 7728167
TI  - Prepaid care. I remember profits ... barely.

PMID- 7728168
TI  - HospitalPulse ... November 1994.

PMID- 7728169
TI  - Camp laparoscopy.

PMID- 7728170
TI  - Education. The learning curve.

PMID- 7728171
TI  - Last wishes. A bittersweet valentine.

PMID- 7728172
TI  - California dreaming. The makings of the biggest HMO deal in history.

PMID- 7728173
TI  - Right woman, wrong job.

PMID- 7728174
TI  - Managed care: far from academic.

PMID- 7728175
TI  - Interpreting the market situation--and a federal ruling--in Utah.

PMID- 7728176
TI  - Speech fluency: effect of age, gender and context.
AB  - The effects of age, gender and task on speech fluency performance in three
      speaking conditions were examined in 78 older (55-92 years) talkers. Results were
      analyzed for significant differences (p < or = 0.01) as a function of age, gender
      and task between speakers groups formed on increasingly older chronological age
      and as compared to a young (25-35 years) control group. The relationship between
      speech fluency and speech rate performance data obtained on the same tasks was
      also examined. Only a few significant effects and/or interactions were found for
      the variables in this study. These findings are discussed and compared to those
      of other recent studies.

PMID- 7728177
TI  - Oral diadochokinesis in neurological dysarthrias.
AB  - Rapid syllable repetitions require alternating articulatory movements and, thus,
      provide a test for oral diadochokinesis. The present study performed an acoustic
      analysis of rapid syllable repetitions in patients suffering from idiopathic
      Parkinson's disease (n = 17), Huntington's chorea (n = 14), Friedreich's ataxia
      (n = 9), or from a purely cerebellar syndrome (n = 13). Four parameters were
      considered: the mean number of syllables per train, the median syllable duration
      with its variation coefficient, and articulatory imprecision in terms of the
      percentage of incomplete closures. Apart from a few subjects with minor motor
      deficits only, in all patients at least one of the four measures of
      diadochokinesis exceeded the normal range. Accordingly, discriminant analysis
      revealed a highly significant difference between controls and patients with
      respect to the considered parameters. Thus, oral diadochokinesis tasks represent
      a sensitive measure of orofacial motor impairment. Moreover, multivariate
      analysis showed that Parkinson's disease and Friedreich's ataxia are
      characterized by a highly specific profile of diadochokinesis performance.

PMID- 7728178
TI  - Improving fundamental frequency modulation in head trauma patients: a preliminary
      comparison of speech-language therapy conducted with and without IBM's Speech
      Viewer.
AB  - This study involves a preliminary comparison of traditional speech therapy for
      head trauma patients with therapy assisted by computer. Two subjects were treated
      in a 'crossover' design to compare the effects of each treatment. While both
      subjects improved, there was no obvious difference in treatment effectiveness.
      However, the computer support provided the measures of treatment efficacy which
      made this comparison possible.

PMID- 7728179
TI  - [Apraxia of the larynx].
AB  - Disturbances of vocal function in patients with apraxia of speech are well known
      in the literature and have often been described. Although apraxia of phonation is
      presumed, only 1 case is mentioned in the literature. We present a 51-year-old
      man (with missing signs of dysarthria and aphasia after spontaneous right
      temproparietal hemorrhagia) who had aphonia and missing respiration during
      speaking, whereas articulation was nearly undisturbed. After differential
      diagnostic exclusion of other central disorders of phonation we classify this
      patient as having apraxia of phonation or laryngeal apraxia.

PMID- 7728180
TI  - [Values of certain prosodic parameters obtain with French-speaking probands
      without communication problems].
AB  - Acoustic data are provided in order to facilitate evaluation of the speech of
      adult patients with prosody disorders such as dysarthria. Forty French-speaking
      subjects between 45 and 75 years of age, with neither neurological disease nor a
      communication disorder, were grouped on the basis of sex and age. Subjects were
      required to produce four series of 20 matched interrogative and declarative
      sentences. Their productions were recorded and analyzed with an IBM Speech
      Viewer. Measures of fundamental frequency, of variation in fundamental frequency,
      of rate over the entire sentence, as well as a measure of intonation (defined as
      the difference in fundamental frequency between the last syllable of matched
      declarative and interrogative sentences) are reported in tables for clinical use.
      These data provide information for the evaluation of the prosody of French
      speaking persons.

PMID- 7728181
TI  - [Premature ovarian failure syndrome].

PMID- 7728183
TI  - [Salpingoscopy:fimbria, ampulla, isthmus].

PMID- 7728182
TI  - [Aspirin and pregnancy: present data and future perspectives].

PMID- 7728184
TI  - [Physiology and disorders of the epididymis].
AB  - The authors review first macroscopic and microscopic anatomy of the epididymis.
      They insist on the labyrinth-like structure of the efferent tubules composing
      part of the caput and they do detail the cellular types lining the epididymal
      tubules. Furthermore, they detail the epididymal functions both with regard to
      the epithelium as to the luminal compartment. The epithelium has mainly a
      function of absorption and secretions. In the luminal compartment the
      spermatozoon is the most important element: it undergoes morphological changes
      all along the transit, correlated with development of fertilizing capacity. The
      epididymis is regulated mainly by androgens. An extensive bibliography completes
      the aforesaid survey.

PMID- 7728185
TI  - [Differential effect of estrogens in target tissues].
AB  - Using ER 1D5 new antibody it is shown that the estrogen receptor has an extra
      nuclear localisation in vascular cells. This work exhibits, moreover, that the
      polymorphism of the estrogen receptor is in part regulated at the translation
      step.

PMID- 7728186
TI  - [Women at high risk for breast cancer: can we define a group of women in France
      who could participate in a prevention trial?].
AB  - Each year, more than 10,000 women die of breast cancer in France. Whatever the
      prevention measures adopted, they must be considered with undivided attention.
      Three factors are associated with an elevated risk of breast cancer: to be 50 or
      over, a family history of breast cancer affecting the mother and at least one
      sister (particularly in the event of early-onset breast cancer), or a personal
      history of benign proliferative breast disease with cellular atypia. High risk
      subjects can be defined as those who regroup these three factors, but this
      definition only applies to a population of 800 women in the entire French
      population. By broadening the definition of high risk subjects to include those
      aged 50 or over, who have a benign proliferative breast disease with cellular
      atypia, and a family history defined as "at least two cases if it concerns their
      mother or sister; or at least three cases, if it concerns aunts, grandmothers or
      daughters", the number of women would rise to 40,000 in France. In this high risk
      population, one in every two women will develop a breast cancer during the next
      30 years. We consider therefore it ethically feasible to propose a prevention
      trial to this group of women in France.

PMID- 7728187
TI  - [Voluntary female sterilization. Viewpoint of the medical advisory assurance
      society].
AB  - The author asks himself the reasons why tubular sterilisation up until now
      tolerated by doctors, insurers, judges, is suddenly put into question on the
      initiative of an insurer. The aggravation of the risk linked to the increase in
      the number of demands for indemnity seems to be one of the reasons. This attitude
      leads to either no longer carrying out this act, or reducing the risk by a more
      rigorous control over the patient selection procedure and the operating
      conditions. A change in the law would be the most satisfactory solution.

PMID- 7728188
TI  - [From the gates of pleasure to pain in its place].

PMID- 7728189
TI  - Effects of insulin and glucose tolerance factor on glucose uptake by yeast cells.
AB  - Addition of mammalian insulin or glucose tolerance factor (GTF), to Saccharomyces
      cerevisiae ATCC 7752, increased 2-deoxyglucose uptake by yeast cells. The
      enhancement was dose-dependent, and also dependent on preincubation of the cells
      with glucose, prior to the addition of the hormone. The effect of insulin on
      glucose uptake by the yeast was very similar to the effect of GTF on these cells.
      Insulin and GTF increased also the growth of yeast cells, while denatured insulin
      or glucagon failed to act. Our findings support the view that both insulin and
      GTF might regulate carbohydrate metabolism in microorganisms.

PMID- 7728190
TI  - Melatonin implant decreases the density of 2[125I]iodomelatonin binding sites in
      the chicken spleen.
AB  - Changes in 2[125I]iodomelatonin binding to the chicken spleen following
      disruption of the normal melatonin rhythm by a slow-release melatonin implant
      were investigated. Melatonin capsules were implanted in 6-week-old male and
      female chickens reared under 12 h light/12 h darkness. The mid-light and mid-dark
      serum melatonin was measured throughout the period of implantation. Spleen weight
      and characteristics of splenic 2[125I]iodomelatonin binding sites were studied
      during the mid-light at 4 or 8 weeks after implantation. Melatonin implantation
      disrupted the normal diurnal rhythm of serum melatonin and elevated the mid-light
      level to the control mid-dark value until 5 weeks after implantation. The
      melatonin implant caused a significant decrease in the density of
      2[125I]iodomelatonin binding sites at 4 weeks after implantation while there were
      no significant changes in the binding affinity. The reduction in
      2[125I]iodomelatonin binding may be a result of down-regulation of the melatonin
      receptors by elevated serum melatonin. Alternatively, it may be due to an
      indirect suppression of 2[125I]iodomelatonin binding sites by the elevated sex
      hormones since melatonin implants increased the levels of testosterone in the
      male and estradiol in the female. Implantation of melatonin capsules
      significantly increased the body and spleen weights in the male chicken. These
      weight changes may be partly explained by the anabolic and erythropoietic action
      of the increased circulating testosterone.

PMID- 7728191
TI  - Melatonin in the control of the estrous cycle of the Indian desert gerbil
      (Meriones hurrianae: Jerdon).
AB  - Daily administration of melatonin for 8 weeks, either in the morning (9 a.m.) or
      late in the afternoon (5 p.m.), resulted in significant prolongation of the
      estrous cycle in the Indian desert gerbil Meriones hurrianae. The gonadosomatic
      index increased significantly (p < 0.01) in the melatonin-treated gerbils
      compared to the control animals. Histological study of the ovaries revealed
      enlargement of follicles and corpora lutea with hypertrophied granulosa cells in
      the melatonin-treated gerbils in comparison to their controls. The data suggest
      that the mechanism involved in the gonadal response to melatonin may not be the
      same in the temperate and tropical species.

PMID- 7728192
TI  - Melatonin in the nemertine worm Lineus lacteus: identification and daily
      variations.
AB  - Melatonin, a well-known pineal substance implicated in conveying photoperiodic
      information in vertebrates, appears to be present as well in the eyes and brain
      of the nemertine worm: Lineus lacteus. The nyctohemeral rhythm was studied, too.
      The identification of melatonin in this new invertebrate species corroborates our
      hypothesis that it may be an evolutionarily conserved molecule, principally
      involved in the temporal transduction of photoperiodic information in all living
      organisms.

PMID- 7728193
TI  - Serial transplants of 7,12-dimethylbenz[a]anthracene-induced mammary tumors in
      Fischer rats as model system for human breast cancer. 3. Quantitative
      ultrastructural studies of the pinealocytes and plasma melatonin concentrations
      in rats bearing an advanced passage of the tumor.
AB  - The aim of the present study was to investigate the ultrastructure of
      pinealocytes and plasma melatonin concentrations in Fischer rats bearing an
      advanced (14th) passage 7,12-dimethylbenz[a]anthracene-induced mammary tumor.
      Quantitative ultrastructural analysis of the cell size and relative volumes of
      various cell organelles as well as the number of dense-core vesicles was
      performed in pinealocytes of the animals killed either during the daytime (15.00
      h) or at night (3.00 h) 1 month after tumor transplantation. No significant
      differences between control and tumor-bearing animals were observed either during
      the daytime or at night. However, plasma melatonin concentrations in tumor
      bearing rats killed at 3.00 h were suppressed by 35% (p < 0.025) when compared to
      the control animals killed at the same time.

PMID- 7728194
TI  - Olfactory micturition reflex. Experimental study in dogs.
AB  - The relation of olfaction to urination was studied in 14 dogs. A stimulating
      surface electrode was applied to the nasal mucosa and a recording electrode to
      each of the external (EUS) and internal (IUS) urethral sphincters.
      Electrostimulation of the nasal mucosal led to diminished EMG activity of IUS,
      and effected no change in the response of the EUS. IUS did not respond to
      stimulation of the anesthetized nasal mucosa. The reproducibility as well as the
      non-response of IUS to stimulation of the anesthetized nasal mucosa point to the
      constancy of a reflex relationship between the IUS and nasal mucosa, which we
      call 'olfactory micturition reflex'. The latency of the reflex (mean +/- SD) was
      49.2 +/- 8.2 ms. It seems that the olfactory micturition reflex induces
      micturition in the absence of a full bladder. This would explain the repeated
      successive urination of small amounts of urine, characteristic of dogs, on
      smelling a uriniferous odor.

PMID- 7728195
TI  - Fever without apparent source on clinical examination, lower respiratory
      infections in children, bacterial infections, and acute gastroenteritis and
      diarrhea of infancy and early childhood.
AB  - This section focuses on issues in infectious disease that are commonly
      encountered in pediatric office practice. Paul McCarthy discusses recent
      literature regarding the evaluation and management of acute fevers without
      apparent source on clinical examination in infants and children and the
      evaluation of children with prolonged fevers of unknown origin. David Bachman
      reviews recent literature about lower respiratory tract infection in children and
      focuses on community-acquired lower respiratory infections and respiratory
      syncytial virus. Eugene Shapiro discusses literature concerning several
      infectious diseases commonly seen in office settings and concerning which recent
      developments are of interest: the hemolytic-uremic syndrome and enterohemorrhagic
      Escherichia coli. Streptococcus pneumoniae resistant to penicillin, infections in
      day care centers, and new antimicrobial drugs. Michael Baron reviews recent
      literature about gastroenteritis and diarrhea of infancy and early childhood and
      discusses diagnosis, complications, pathogenesis and physiology, epidemiology,
      and treatment.

PMID- 7728196
TI  - Neonatal group B streptococcal infections.
AB  - Group B streptococci remain a leading cause of life-threatening neonatal
      infection worldwide. The current estimate of incidence in the United States is
      1.8 cases per 1000 live births, with a case-fatality ratio of 10% to 20%.
      Advances in understanding of the pathogenesis of septic shock and meningitis are
      yielding new approaches to the treatment of these serious infections. Selective
      intrapartum chemoprophylaxis with ampicillin has been shown to be both effective
      and cost effective and is gaining more widespread acceptance as a preventive
      measure. Conjugate vaccines consisting of type-specific group B streptococci
      capsular polysaccharides coupled to tetanus toxoid or protein membrane antigens
      of group B streptococci have been shown to prevent neonatal infection in a mouse
      model of maternal immunization. Such vaccines are now in trials of safety and
      immunogenicity in humans.

PMID- 7728197
TI  - Herpes simplex virus infections in children.
AB  - This paper focuses on the advances that have been made in our understanding of
      the pathogenesis, diagnosis, treatment, and prevention of herpes simplex virus
      (HSV) infections. Insights have been gained into the immune defense mechanisms
      that may be active in protecting the fetus from HSV infection. An animal model
      that closely mimics human neonatal HSV disease may permit exploration of novel
      interventional strategies. Brain biopsy for the diagnosis of HSV encephalitis has
      been supplanted by polymerase chain reaction detection of HSV DNA in the
      cerebrospinal fluid and, to a lesser extent, by detection of intrathecal HSV
      specific antibodies. Prolonged immune activation within the nervous system
      following HSV encephalitis has been demonstrated and may implicate immune
      activation in the pathogenesis of HSV-induced neurologic damage. The continuing
      emergence of antiviral drug resistance further underscores the need for new
      strategies for treatment and prevention of HSV infections.

PMID- 7728198
TI  - Enterovirus infections in children.
AB  - International cooperation and widespread use of trivalent oral poliovaccine has
      almost eliminated paralytic poliomyelitis from developed countries and is now
      dramatically decreasing the disease in developing countries. The remarkable
      results are based on the strategies recommended by the World Health Organization,
      which include national mass campaigns for administering oral polio vaccine to all
      children younger than 5 years of age, enhanced surveillance to find patients with
      acute flaccid paralysis, creating a network of laboratories for viral diagnosis,
      and targeted immunization to populations in endemic areas. Another remarkable
      advance in clinical and research fields of enterovirus infections is the
      development of molecular genetic technologies such as polymerase chain reaction
      and in situ hybridization assays. A cloned enterovirus complementary DNA prepared
      from the highly conserved 5' region of the enterovirus genome can be used for
      rapid and sensitive group-specific diagnosis of enterovirus infections. This
      complementary DNA is currently being used to study the molecular mechanisms in
      the pathogenesis of enteroviral heart disease; lesions in acute and chronic
      myocarditis and even in end-stage dilated cardiomyopathy may be associated with
      replication of enteroviruses.

PMID- 7728199
TI  - Influenza immunization: time to stop the charade.

PMID- 7728200
TI  - Hematology and oncology.

PMID- 7728201
TI  - The spleen in children.
AB  - The spleen contributes importantly to the normal and pathologic removal of blood
      cells from the circulation and to defense against infection with encapsulated
      bacteria. Surgical splenectomy provides efficacious treatment for a number of
      pediatric disorders but is associated with perioperative morbidity and a life
      long risk of overwhelming infection. Alternatives to conventional splenectomy
      include laparoscopic splenectomy, partial splenectomy, partial splenic
      embolization, and autologous splenic transplantation. Sickle cell disease is the
      most common cause of functional asplenia in children. Asplenia develops during
      infancy in many infants with sickle cell anemia, and prophylactic penicillin
      markedly reduces mortality from pneumococcal infection. In contrast, recent
      evidence suggests that children with sickle-hemoglobin C disease do not develop
      functional asplenia before 3 to 4 years of age and thus may not benefit from
      penicillin prophylaxis. Recommendations for the treatment of asplenic patients
      include pneumococcal, Haemophilus influenzae type b, and meningococcal
      immunizations, antimicrobial prophylaxis for selected patients, and prompt
      evaluation and aggressive treatment of acute febrile illness.

PMID- 7728202
TI  - Advances in decontamination of blood components.
AB  - Despite improved pretransfusion donor evaluation and testing, there is still
      residual risk of transfusion-associated viral infectious disease. Moreover, other
      important infectious pathogens, including bacteria, protozoa, and nonenveloped
      viruses, are not detected in current testing programs. Recent investigations from
      several laboratories have stimulated interest in decontamination of blood
      products as an additional means to further enhance the safety of blood
      transfusion. Furthermore, because testing is a retrospective strategy, a robust
      decontamination process could provide prospective protection against new
      pathogens that may enter the blood donor population. Recent advances in
      decontamination of fresh frozen plasma, plasma derivatives, platelet
      concentrates, and erythrocytes are reviewed. The introduction of solvent
      detergent-treated plasma fractions marks an important advance in transfusion
      safety. Other technologies for cellular components are emerging to address
      transfusion-associated infectious disease transmission.

PMID- 7728203
TI  - Cord blood as an alternative source for stem and progenitor cell transplantation.
AB  - Blood collected from the umbilical cord and placenta at the birth of a child is a
      rich source of immature blood cell elements and has been used clinically as an
      alternative source of transplantable stem and progenitor cells. Studies on the
      proliferative and replating capacities of cord blood stem and progenitor cells
      have documented their extensive capacity for division and self renewal. Studies
      on the immune cells in cord blood have shown them to be less immunologically
      reactive in a number of situations. These characteristics are consistent with the
      experience in children receiving HLA-matched sibling cord blood cells, in which
      these cells have been transplantable in a large number of clinical disorders with
      low or absent graft-versus-host disease. Stem and progenitor cells from cord
      blood are efficiently transduced with new genetic material by retroviral and
      adeno-associated viral vectors and may be of efficacy in the future for
      autologous gene therapy approaches to treat disease. Efforts in banking of
      cryopreserved cord blood cells have been undertaken, and a number of such stored
      samples have been used for fully and partially HLA-matched unrelated
      transplantation. Efforts to better understand the cells in cord blood and their
      clinical utility are continuing.

PMID- 7728204
TI  - The current status of gene therapy using hematopoietic stem cells.
AB  - Gene transfer into hematopoietic stem cells may provide a novel treatment for a
      number of congenital hematologic and immunologic diseases. Retroviral vectors are
      currently the most effective gene transfer system, but they have significant
      limitations. New approaches using other vector systems, stem cells from umbilical
      cord blood, or cytokine-mobilized peripheral blood stem cells may increase gene
      transfer efficiency. The current capabilities and obstacles to successful
      implementation of gene therapy with hematopoietic stem cells are discussed.

PMID- 7728205
TI  - Tuberculosis in children.
AB  - Tuberculosis in children is a growing problem, both globally and in many
      industrialized countries. With a rising incidence, clinicians will again face the
      challenge of the myriad presentations of tuberculous disease. Multidrug
      resistance and HIV coinfection present additional complications. Renewed interest
      in tuberculosis among scientists has led to progress in our understanding of
      antimycobacterial effector mechanisms, the regulation of Th1 and Th2 immune
      responses, virulence factors, and the potential for immunotherapeutic agents to
      reduce the duration of antituberculous therapy.

PMID- 7728206
TI  - Brain tumors in children.
AB  - Brain tumors are the most common form of solid neoplasm of childhood. Progress in
      the treatment of childhood brain tumors has been frustratingly slow, especially
      in comparison with other pediatric malignancies. The biology of primary pediatric
      brain tumors of childhood is just being unraveled. Chemotherapy is a major
      component of the treatment of many forms of childhood primary central nervous
      system tumors and is being used in attempts to improve survival and to delay or
      decrease the amount of radiotherapy needed. Despite the use of more aggressive
      radiotherapy approaches and intensified chemotherapy approaches, outcome remains
      dismal for brain stem gliomas and high-grade cortical gliomas. Many unsettled
      issues exist concerning the treatment of childhood low-grade gliomas.

PMID- 7728207
TI  - A 5-week-old infant with cyanosis, diarrhea, and dehydration. Case report.

PMID- 7728208
TI  - Screening and ultrasound for neonatal hip instability.

PMID- 7728209
TI  - Initial screening and diagnosis of and referral for developmental dysplasia of
      the hip.
AB  - The continued diagnosis of cases of late developmental dysplasia of the hip
      reaffirms the failure of initial clinical neonatal screening programs. Even the
      identification of an "at risk" patient profile will not eliminate the late
      diagnoses, but referral of these patients will ensure that up to 50% of late
      diagnoses can be eliminated. The role of ultrasound as a screening diagnostic
      tool has not, at this time, been confirmed to eliminate late diagnoses. Its use,
      however, has led to an increased incidence of treatment with the recognition of
      the sonographic "immature hip." This, in turn, will increase the number of
      complications of treatment with iatrogenic avascular necrosis. Therefore, the
      ideal elimination of all late developmental dysplasia of the hip referrals
      remains the unattained goal.

PMID- 7728210
TI  - Office evaluation and treatment of finger and hand injuries in children.
AB  - Injury is our children's greatest health problem, and pediatricians will
      frequently see finger and hand injuries in the office and emergency room. Many of
      these will be fingertip crush injuries, which are quite common in toddlers and
      are often undertreated. Pediatric finger and wrist fractures and sprains
      generally do well but require proper diagnosis and treatment. Innocent-looking
      wounds from glass lacerations may disguise extensive damage to underlying nerves,
      arteries, and tendons. Advances in microsurgery allow replantation of distal
      amputations even in young children and infants, although often not without
      complications. Thermal injuries and animal bites require early and aggressive
      treatment. As with many pediatric hand injuries, these injuries should be
      preventable, and the adverse consequences can be minimized with appropriate
      diagnosis and management.

PMID- 7728211
TI  - Evaluation of limp in children.
AB  - The limping child is a common and often challenging problem for the pediatrician.
      A practical guide is given to the evaluation of normal and abnormal gait,
      important historical and physical findings, and laboratory and radiographic
      studies. The differential diagnosis is quite variable, ranging from benign to
      very serious life- or limb-threatening possibilities. Some of the more common and
      important conditions are summarized.

PMID- 7728212
TI  - Slipped capital femoral epiphysis in children.
AB  - Two new classification schemes have been described for slipped capital femoral
      epiphysis (SCFE); both involve the question of stability and are probably more
      prognostic than the traditional acute or chronic classification. The prevalence
      of bilaterality is approximately 33%, and two recent series regarding bilateral
      SCFE recommend frequent follow-up after a child presents with a unilateral SCFE,
      but they do not recommend prophylactic pinning of the normal hip. In the case of
      a child with an underlying endocrine disorder who presents with a unilateral
      SCFE, however, strong consideration should be given to prophylactic pinning of
      the opposite hip. The most commonly accepted method of fixation at this time is
      in situ pin fixation with a single central screw. The screw head should be no
      more than 1.5 cm from the cortex of the femur to prevent windshield-wiper
      loosening. Chondrolysis, a complication of both untreated and treated SCFE, has a
      more favorable prognosis than idiopathic chondrolysis.

PMID- 7728213
TI  - A review for pediatricians on limb lengthening and the Ilizarov method.
AB  - As recently as 1986, limb lengthening in children was considered by most North
      American orthopedic surgeons to be both dangerous and impractical. Previous
      attempts were plagued by unacceptably high rates of serious complications such as
      nerve palsy, deep infection, malunion, broken hardware, and stiff joints. With
      the recent introduction of the Russian Ilizarov method and apparatus for limb
      lengthening, a tremendous groundswell of interest has risen. Despite a steep
      learning curve, many Western centers have now reproduced Ilizarov's clinical
      results. The important advances over prior methods are partly biologic and partly
      hardware related. Ilizarov's principles require a minimally invasive, low-energy
      osteotomy, stable external fixation, a latency period before commencing
      distraction, and gradual lengthening of 1 mm/d in divided doses (0.25 mm four
      times per day). The article reviews the background of this new technique and
      provides an update on results reported over the past year. There is disagreement
      regarding precise indications for limb salvage (lengthening) of congenital limb
      deficiencies versus amputation. The role of extended lengthening in dwarfism also
      remains controversial.

PMID- 7728214
TI  - Neuronal ultrastructural abnormalities in a patient with frontotemporal dementia
      and motor neuron disease.
AB  - Motor neuron disease (MND) can be associated with frontotemporal dementia (FTD)
      and circumscribed lobar atrophy of frontal and temporal lobes. Neuropathological
      correlations were sought in postmortem studies from a woman with these associated
      conditions. Cerebral blood flow imaging and autopsy showed cortical abnormalities
      in the frontal and temporal lobes, but typical argyrophilic Pick's bodies were
      absent and ubiquitin-positive neuronal cytoplasmic inclusions were rare. However,
      hematoxylin and eosin staining revealed eosinophilic, granular, central
      cytoplasmic 'clearing' in most neurons of the substantia nigra and in cervical
      anterior horn cells. Electron microscopy showed that these neurons contained a
      central cytoplasmic zone cleared of neuromelanin and normal cytoplasmic
      organelles containing small mitochondria with matrix inclusions and randomly
      oriented filamentous material. A mitochondrial dysfunction or defective transport
      of mitochondria into axonal processes needs to be studied as a potential cause
      for the coassociation of MND and FTD.

PMID- 7728215
TI  - Elevated alpha 1-antichymotrypsin serum levels in a subset of nondemented first
      degree relatives of Alzheimer's disease patients.
AB  - A portion of Alzheimer's disease (AD) patients have elevated serum levels of the
      acute phase reactant alpha 1-antichymotrypsin (A1ACT) compared to age-matched
      controls. We measured serum levels of A1ACT in AD patients, age-matched controls,
      Down's syndrome patients, and nondemented first-degree relatives of AD patients.
      Significantly elevated levels of A1ACT were found in both AD patients and first
      degree-relatives. In AD patients, serum A1ACT concentrations decreased with
      increasing severity of cognitive impairment. These results may suggest that
      inflammatory phenomena may be an early component of AD pathophysiology.

PMID- 7728216
TI  - Relative roles of plaques and tangles in the dementia of Alzheimer's disease:
      correlations using three sets of neuropathological criteria.
AB  - We have performed a quantitative analysis of the amyloid load (plaques), neuritic
      plaques and neurofibrillary tangles (NFT) in the frontal, temporal and parietal
      association cortices of autopsied brains from 49 prospectively evaluated patients
      with Alzheimer's disease (AD) diagnosed according to three sets of published
      pathological criteria. These patients had been assessed clinically with
      psychological testing of cognitive abilities within 6 months of death.
      Correlations were sought between severity of pathological change and cognitive
      status before death, duration of disease and age at death. Using Khachaturian and
      CERAD criteria highly positive correlations were obtained between the extent of
      cognitive deficit and the density of NFT in frontal and parietal lobes. The
      percentage area of cortex occupied by amyloid in the parietal lobe was correlated
      to the cognitive deficit only in the CERAD-diagnosed cases. The density of all
      amyloid plaques (AP) showed no correlation with the extent of cognitive deficit,
      but the densities of neuritic plaques did correlate with cognitive deficit. Both
      amyloid load and tangle densities were positively correlated with disease
      duration. All these correlations were reduced or absent in a subgroup of cases
      fulfilling the Tierney et al. A3 diagnostic criteria for AD. We found no
      pathological measure that correlated with the age of patients at death. Amyloid
      loads and NFT densities showed highly significant but selective positive
      correlations, the most striking being between temporal lobe NFT density and
      frontal and parietal lobe amyloid load and between temporal lobe NFT density and
      frontal and parietal lobe NFT densities. Correlations involving AP density as a
      measure of amyloid load were almost always less significant than those involving
      the percentage area of cortex occupied by amyloid, suggesting that the latter
      measures amyloid load more accurately. However, the highest correlations of NFT
      densities were with neuritic plaque densities. Overall this study highlights the
      relevance of neuritic changes (revealed by NFT and neuritic plaques) and the
      irrelevance of amyloid plaques to the dementia of AD.

PMID- 7728217
TI  - Correlations between cognitive impairment, middle cerebral artery flow velocity
      and cortical glucose metabolism in the early phase of Alzheimer's disease.
AB  - In a previous transcranial Doppler (TCD) study, we demonstrated a decrease in
      blood flow velocity in the proximal tract of the middle cerebral artery (MCA) in
      patients with Alzheimer's disease (AD). In these patients there was also an
      asymmetry in blood flow velocity which positively correlated with the cognitive
      asymmetry often seen in the early phase of AD. In this study we found a
      correlation between the absolute values and asymmetry indexes of MCA blood flow
      velocity with adjusted metabolic values and asymmetry indexes of the relative
      cortical frontotemporoparietal (FTP) areas, evaluated by FDG-PET, and with
      neuropsychological asymmetry indexes. Patients with prevalent visuospatial
      deficits (right hemisphere dysfunction) showed significant decreases in right MCA
      blood flow velocity and right FTP cortical glucose hypometabolism, whereas in
      patients with prevalent language deficits (left hemisphere dysfunction), these
      signs were observed on the other side. In AD patients, the decrease of blood flow
      velocity in MCA might be due to reduced metabolic demands in the temporoparietal
      cortical areas primarily affected by AD.

PMID- 7728218
TI  - Chronic obstructive pulmonary disease and associated patterns of memory decline.
AB  - The relationship between chronic obstructive pulmonary disease (COPD) and
      cognitive functioning was analyzed in a study with 50 aging patients. A complex
      pattern of interactions was identified between emotional and cognitive
      functioning and chronic respiratory disease when the effects of age, sex, type
      and severity of disease were controlled. These patients did not show any global
      and diffuse cognitive impairment. Only a portion of COPD patients (about 30%)
      evidenced memory impairment which was confined to immediate memory. Memory
      impairment found in these patients did not appear to be associated with those
      changes present in the aging process but was mainly related to those specific
      clinical and instrumental parameters which are considered valid indicators of
      respiratory efficiency. Two types of cognitive and emotional problems were
      identified. A progressive stage-dependent set of characteristics was associated
      with the course of the disease and a fluctuating, probably reversible state
      dependent set of characteristics was associated with the temporary condition of
      the patients during the period of examination. Patients who had received more
      recent medical treatment or who were under protection of vaccination for
      influenza showed a better cognitive and emotional efficiency.

PMID- 7728219
TI  - Visuospatial performance in very old demented persons: an individual difference
      analysis.
AB  - This study examines selected demographic, psychometric, and biological measures
      as predictors of visuospatial performance in a sample of 98 persons with mild to
      moderate dementia. Visuospatial performance was measured using standardized
      neuropsychology instruments, namely: Poppelreuter's figures, the clock test, and
      block design. Although multiple measures were initially correlated with
      performance on the selected visuospatial tests, the Mini-Mental State Examination
      was the exclusive predictor of Poppelreuter's figures and the clock test scores.
      For block design, years of education also contributed to the prediction model,
      but only among mildly demented persons. These results suggest that disease
      severity plays a dominant role in the prediction of visuospatial performance in
      dementia, particularly in more advanced stages of the disease. The differential
      role of education in predicting block design performance in mild vs. moderate
      dementia was also highlighted.

PMID- 7728220
TI  - Education and occupation as risk factors for dementias of the Alzheimer and
      ischemic vascular types.
AB  - Education and occupation as sociodemographic risk factors for dementias of the
      Alzheimer (DAT) and ischemic vascular types (IVD) were evaluated by two case
      series studies. Cases were compared to well-evaluated individuals identified as
      healthy normals acting as controls. There were 150 patients with probable DAT,
      102 patients with probable IVD, and 188 neurologically and cognitively normal
      subjects. Logistic regression indicated that for DAT, education with occupation
      was the best predictor (OR, 1.51; 95% CI, 1.23-1.87). For IVD, the two predictors
      were: education with occupation (OR, 1.84; 95% CI 1.38-4.50) and education with
      gender (OR, 3.40; 95% CI, 1.29-8.92). We conclude that risk of dementia is
      increased in those with limited educational background and occupational
      achievement.

PMID- 7728221
TI  - Cell-cycle-dependent abnormal calcium response in fibroblasts from patients with
      familial Alzheimer's disease.
AB  - Change in calcium response was studied to clarify the pathological process of
      Alzheimer's disease (AD). Cultured fibroblasts from patients with familial
      Alzheimer's disease (FAD; n = 6), sporadic Alzheimer's disease (SAD; n = 4), and
      age-matched healthy control subjects (n = 4) were studied with an ACAS
      Interactive Laser Cytometer (ACAS-470). Fibroblasts from two independent families
      with FAD (OS-1, and OS-2 families) showed a suppressed calcium response after
      stimulation by 100 nM bradykinin (BK) 100 nM vasopressin (VP) or 10% FCS in
      Ca(2+)-free condition compared with control fibroblasts at 48 h after plating.
      However, on the 7th day after plating, the abnormal calcium response was no
      longer observed. The height of the calcium peak showed periodic variation,
      indicating a relationship of calcium response with the cell cycle. When
      fibroblasts from OS-1 and OS-2 families were arrested in S phase, they showed a
      significantly suppressed calcium peak after BK stimulation. However, when those
      fibroblasts were arrested in other phases, they showed the same calcium peak as
      the other cells. The suppression of calcium response in S phase was
      indistinguishable from the calcium suppression induced by A23187 administration.
      Since Hardy type mutation on amyloid precursor protein gene is found in the OS-1
      family, the observed abnormalities in calcium response might be related with
      pathological processing of amyloid precursor protein in AD. The reported abnormal
      calcium response, which is observed most obviously in fibroblasts in S phase, may
      indicate participation of the cell-cycle-dependent process in the pathology of
      AD.

PMID- 7728222
TI  - Proceedings of International Symposium of Allergy and Asthma Prevention. Berlin,
      April 1993.

PMID- 7728223
TI  - Natural course of asthma and allergy in childhood.

PMID- 7728224
TI  - Atopic diseases in infancy. The German multicenter atopy study (MAS-90).

PMID- 7728225
TI  - Atopy prevention in childhood: the role of diet. Prospective 5-year follow-up of
      high-risk infants with six months exclusive breastfeeding and solid food
      elimination.

PMID- 7728226
TI  - Is maternal diet worthwhile?

PMID- 7728227
TI  - Dietary manipulations in infants and their mothers and the natural course of
      atopic disease.

PMID- 7728228
TI  - Early solid food diet and eczema in childhood: a 10-year longitudinal study.
AB  - The relationship between early solid feeding in the first four months and risks
      of eczema in childhood was examined in a birth cohort of 1265 children studied to
      the age of 10 years. The major findings of this analysis were: 1) children
      exposed to a diverse solid food diet during their first four months had risks of
      eczema in early childhood which were about 1.6 times those of children who were
      not introduced to solid food by age four months. These associations persisted
      when a range of confounding factors (including family history of atopic disease,
      infant milk diet (breast/bottle) and family social background factors) were taken
      into account. 2) Similar associations between early infant diet and risks of
      chronic and recurrent eczema up to the age of ten years were also found. It was
      estimated that after adjustment for confounding factors, children exposed to an
      early diverse solid food diet had risks of eczema which were over 2.5 times those
      of children not introduced to solid feeding. These results are generally
      consistent with the hypothesis that early exposure to a diverse solid food diet
      may increase risks of eczema in children who are susceptible to this condition.

PMID- 7728229
TI  - Childhood asthma and the environment.

PMID- 7728230
TI  - Environmental causes of asthma in children.

PMID- 7728231
TI  - The Isle of Wight study, an approach to allergy prevention.

PMID- 7728232
TI  - Socio-economic burden of asthma, allergy, and other atopic illnesses.
AB  - Asthma and atopic illness account for a substantial burden of social morbidity.
      The purpose of this brief report will be to provide an overview of the different
      dimensions to the socio-economic burden of asthma and other atopic diseases and
      suggest areas where future research in this area may advance our understanding of
      the impact of various treatment strategies of these diseases. While there are
      occasional studies which describe the full dimensions of this social and economic
      burden, more studies are needed to complete our understanding of this burden
      especially studies that investigate the relative cost-effectiveness of medical
      and non-medical interventions. These studies will provide the infrastructure to
      rationally examine the optimal cost-effective strategies for these illnesses. In
      particular economic studies are needed to examine how best to balance resource
      expenditures for preventive versus pharmacologic control. Use of health economic
      methods will provide insights into the most efficient design and implementation
      of current disease control, with potentially concomitant reductions in costs and
      social burden for atopic illnesses, including asthma.

PMID- 7728233
TI  - Anxiety, misinformation and greed.

PMID- 7728234
TI  - Legal liability and re-use of disposables.

PMID- 7728235
TI  - De-coding the code of conduct chaos.

PMID- 7728236
TI  - Here it comes again: the specialist staff shortage cycle.

PMID- 7728237
TI  - Emergency transfer of sick neonates.

PMID- 7728238
TI  - Nurses and medication. Part 6. Ritual+workloads = medication error.

PMID- 7728239
TI  - HIV/AIDS exhibition a first for Australia.

PMID- 7728240
TI  - [Assessment of nursing activities in the program of control of Hansen's disease
      in the state of Sao Paulo].
AB  - The present study assesses nursing actions in the Leprosy Control Program in the
      state of Sao Paulo. Nursing care, education, epidemiological control and
      administrative actions are primitive. Revision of practices being developed in
      the new model of health care are necessary.

PMID- 7728241
TI  - [Lifestyle and work of nursing personnel and back pain].
AB  - This paper is part of a broader study. In order to describe life style and
      occupational history possibly related to back pain, 75 female workers of the
      nursing staff from a University Hospital were interviewed during clinical
      evaluation.

PMID- 7728242
TI  - [Public health nursing, pedagogical and agricultural advice in a rural community
      of landless settled people: report of an experience].

PMID- 7728243
TI  - [Understanding AIDS in Brazil].

PMID- 7728244
TI  - [The patient with essential hypertension. Nursing diagnosis and advice in
      ambulatory care].
AB  - The hypertensive patient: nursing diagnoses and intervention at the ambulatory
      level. The purpose of this study was to analyze nursing diagnoses in adults with
      essential hypertension and the nursing interventions patient education is an
      urgent necessity. There was no reliable parameter to evaluate nursing
      intervention.

PMID- 7728245
TI  - [Historical population laws: theory for the understanding of human reproduction].
AB  - Beginning with the concept of population, the author develops the historical laws
      that rule demographic development, which is an expression of the particular forms
      of organization in different human societies throughout history.

PMID- 7728246
TI  - [The triad configuration, humanist-existential-personal: a theoretical and
      methodological approach to psychiatric and mental health nursing].
AB  - The author establishes a research line based on a theoretical-methodological
      referential for the qualitative investigation of psychiatric nursing and mental
      health. Aspects of humanist and existential philosophies and personalism were
      evaluated integrating them in a unique perspective. In order to maintain the
      scientific method of research in this referential the categorization process
      which will be adopted in this kind of investigation was explained.

PMID- 7728247
TI  - [Mental and physical stress of auxiliary nurses: analysis of management].
AB  - Seeking a better understanding of job stress, auxiliary nurses were evaluated in
      General Hospitais Belo Horizonte. The emotional stress which accompanies
      auxiliary nurses caring for the sick and easing physical and mental suffering
      effects their own mental state and physical health. Elements that cause suffering
      and diseases can be attenuated or intensified depending on labor relations.
      However, organizations have not been concerned about working conditions. This
      paper suggests some protective safety and health measures that can improve labor
      relations and consequently reduce the suffering of working in hospitals.

PMID- 7728248
TI  - [Need of university students for a mental health orientation and education
      service].
AB  - The curative feature of health of university students has gained more attention.
      This study evaluated the needs of university students for an orientational and
      educational service on mental health. For mental health orientation and
      education, an individual consultation service, was implanted as well as lectures
      about the theme. This project gathered data and information important to the
      effective institutionalization of the service.

PMID- 7728249
TI  - [Alternating shifts: mental fatigue in nurses].
AB  - The goal of the present study was to detect signs and symptoms of mental fatigue
      in nurses working in the hospital with shift schedule. The signs and symptoms of
      mental fatigue were measured by a subjective indicator, composed of a check list
      and two objective indicators called critical frequency of light fusion (Flicker)
      and Reaction Time to auditive stimulus (RTs). During fifteen consecutive days,
      morning, afternoon and night shifts of 12 nurses working in three different units
      of a university hospital were analyzed. The great rotation in work schedule, when
      in just one week a nurse can work up to three different shifts, is hazardous to
      the health, social, familiar and professional life of those nurses, who were not
      satisfied with the work schedule adopted by the institution and showed signs and
      symptoms of mental fatigue. The incidence of symptoms was greater for the night
      than for the morning shift which was greater than the afternoon shift and they
      frequently showed irritabilig and sleep disturbances. Indications of mental
      fatigue were detected by Flicker verification in the following order: morning
      shift greater than night shift which was greater than afternoon shift. On the
      other hand, using RTs the following indices of fatigue were detected: greater in
      the evening shift than morning shift which was greater than the afternoon shift.

PMID- 7728250
TI  - [Study of pregnant women at a municipal health center in Botucatu, Sao Paulo.
      Relationship between low maternal weight and low birth weight].
AB  - This study evaluated a group of 15 low-weight pregnant women, who underwent
      prenatal medical examinations at a City Health Center on the outskirts of
      Botucatu-SP, using the "Rosso Curve", and compared them with a group of 8 normal
      weight pregnant women, also screened by the same institution at the same prenatal
      service. We verified that the children born from normal-weight pregnant women
      weighted an average 118 g more than those of low-weight pregnant women.
      Independent of the mother's weight, those born from mothers whose height was
      greater than 155 cm and were non-smokers weighed more. Pregnant women of normal
      weight had, on average, an additional 2 weeks of pregnancy: Amongst those born of
      low weight pregnant women, we noted a connection between medium birth weight and
      an increase on the uterine height curve X gestational age. There was no
      connection between maternal anemia and interpartial intervals less than to 2
      years and birth weight.

PMID- 7728251
TI  - [Investigation of the school life of students entering an undergraduate nursing
      course at a Brazilian school from 1984-1988].
AB  - An investigation of professional nursing training was carried out by examining
      the time spent in nursing school of the 336 students registered at the Nursing
      College of Ribeirao Preto at University of Sao Paulo from 1984 to 1988. The data
      showed that during this time 197 (58.6%) students graduated, two students were
      still enrolled, 26 (7.7%) transferred to other schools, 15 (4.4%) officially
      interrupted their course of study, and 96 (28.5%) abandoned the school.

PMID- 7728252
TI  - Ambulatory care nursing: the wave of the future, not a day at the beach.

PMID- 7728254
TI  - Children of divorced parents.

PMID- 7728253
TI  - Outcomes and geriatric research. Interview by Cynthia Saver.

PMID- 7728255
TI  - Bioethics update: HIV testing.

PMID- 7728256
TI  - Colors of the spectrum. Diabetes nurse educator.

PMID- 7728257
TI  - Coming off isolation.

PMID- 7728258
TI  - So what's to laugh about?--humor in nursing.

PMID- 7728259
TI  - Management perspectives. Trouble recruiting nurses as head nurse of our medical
      center's newly opened subacute care units.

PMID- 7728260
TI  - Jumping on the subacute care bandwagon.

PMID- 7728261
TI  - Colors of the spectrum. Open heart: cardiovascular ICU nursing.

PMID- 7728262
TI  - Real life critical care.

PMID- 7728263
TI  - Critical care sampler.

PMID- 7728264
TI  - Safety monitoring and epidemiological surveillance of blood transfusion in
      Europe.

PMID- 7728265
TI  - [Platelet transfusions in neonatology].
AB  - Thrombocytopenia occurs in 20% to 40% of infants admitted to a neonatal intensive
      care unit. Approximately 30% of the newborns with severe thrombocytopenia below
      50.10(9)/l platelets receive platelet transfusions. The etiology may be:
      bacterial infection, DIC and immune mediated thrombocytopenia. The consequences
      of thrombocytopenia are significant risks of severe intracranial hemorrhage and
      neurologic morbidity. Therapeutic platelet transfusions are given to actively
      bleeding neonates with less than 50.10(9)/l platelets. Prophylactic platelet
      concentrates are usually given to infants with platelets counts below 20.10(9)/l.
      The standard platelet concentrate (CMV-negative donor) is the product of choice
      for newborns. Fetal intracranial hemorrhage is possible as soon as 20 weeks of
      gestation in allo-immune thrombocytopenia. Actually percutaneous umbilical blood
      sampling is very useful to measure fetal platelets count in order to decide in
      utero maternal platelet transfusion. Maternal irradiated plateletpheresis
      concentrates are preferentially infused in this indication. At the end of
      pregnancy, cesarean section is preferred to normal vaginal delivery if fetal
      thrombocytopenia below 100.10(9)/l is observed. In pregnant women with auto
      immune thrombocytopenia, the decision to carry out percutaneous umbilical blood
      samples should be weigh relatively to the 3-5% estimated risk of serious
      consequences. Platelets transfusions are particularly successful in immune
      thrombocytopenia but less effective in other clinical circumstances.

PMID- 7728266
TI  - [Platelet transfusions in medullary insufficiency].

PMID- 7728267
TI  - [Ineffectiveness of platelet transfusions in the course of thrombocytopenia of
      central origin. Work Group coordinated by ANDEM].
AB  - This study, conducted under the auspices of ANDEM, was aimed at determining the
      reasons for the inefficacy of platelet transfusions for thrombocytopenia of
      central origin, and to establish recommendations for therapy and prevention. It
      was based on a critical review of the literature. Three main causes of inefficacy
      were identified: an immunological conflict (mainly anti-HLA alloimmunization),
      clinical status, and the quality of platelet preparations (especially storage
      time). Our recommendations depend on several factors, such as the degree of
      urgency, the cause of platelet refractoriness, clinical status and the
      availability of platelet preparations. The mainstay of the recommendations is
      prevention, based on the quality of platelet preparations (as fresh as possible,
      in adequate number preferably obtained by apheresis and ABO compatible) and on
      the prevention of anti-HLA alloimmunization.

PMID- 7728268
TI  - Platelet transfusion refractoriness--prevention and therapeutical approaches.

PMID- 7728269
TI  - [Antibody idiotypes--contribution of the network of interactions between
      idiotypes and anti-idiotypes to the regulation of antibody production].

PMID- 7728270
TI  - [Use of immunoglobulins G in the treatment of nervous system diseases].
AB  - Short term and long term beneficial effects of IgG administration have been
      studied in 4 groups of neuro-immunological diseases: Polymyositis,
      dermatomyositis and myasthenia. Peripheral neuropathies (myelinopathies),
      primarily in Guillain-Barre syndrome and in chronic inflammatory polyneuropathy.
      Children intractable Epilepsy. Multiple Sclerosis. Actual results are in favor of
      an objective and marked improvement (after 1 or 2 months) in the first 2 groups
      using intravenous IgG. In M.S. patients, the short term treatment of bouts
      (especially: optic neuritis) seems promising. Results of the only one long term
      (later than 10 years) trial are in favor of a significant slowing of the
      progression of M.S. comparatively to the predictive curve of disease.

PMID- 7728271
TI  - Safety monitoring and epidemiological surveillance of blood transfusion in the
      United States.
AB  - Safety monitoring and epidemiological surveillance of blood transfusion in the
      United States is complex and involves government agencies and independent
      organizations. Several systems of control are in place nationwide to ensure that
      blood, blood components, and plasma derivatives meet prescribed standards.
      Control and surveillance of drugs that are biologics, which include human blood,
      blood components and plasma derivatives, are exercised by the Food and Drug
      Administration. Epidemiological surveillance involves several agencies and
      organizations that constitute a network capable of rapidly detecting unusual
      adverse events.

PMID- 7728272
TI  - [Ionizing radiations and the antimicrobial resistance of the body in warm-blooded
      animals].
AB  - Various aspects of ionizing radiation action on microorganisms and course of endo
      and exogenous infections are considered. The immune response is discussed from
      the standpoint of its significance in development of infectious-inflammatory
      processes under conditions of radiation of a microorganism and higher radiation
      background. Quantitative and functional changes in the immune system of the
      organism subjected to radiation are discussed in detail and peculiarities of
      these changes under low doses of radiation are shown. The analysis of the data
      obtained has confirmed a decrease of the natural resistance of organism to
      various infectious agents of endo- and exogenous origin under the effect of
      ionizing radiation; the main reason of that is disturbance of the immunity
      system, particularly at the cellular level.

PMID- 7728273
TI  - [The growth characteristics of the yeast Saccharomyces cerevisiae on media
      containing ethanol and saccharose].
AB  - Joint effect of various concentrations of alcohol and saccharose in the medium as
      well as the influence of temperature are studied under conditions of batch
      cultivation of Saccharomyces cerevisiae. It has been found that saccharose added
      to the medium in the amount exceeding 1% is assimilated less efficiently. So, it
      is not expedient to exceed the above concentration in industrial nutrient media
      with 10-12 vol. % of ethanol. The biomass yield within 18-22 degrees C depends
      only on the alcohol amount in the medium. A further rise in temperature to 35
      degrees C induces its inhibitory effect ever growing with the ethanol
      concentration in the medium. Mathematical modeling shows basic regularities of
      the growth process which permit predicting behaviour of the culture in the
      studied factorial space. Optimal values of saccharose concentrations and
      cultivation temperature for the most efficient cultivation of yeast on the
      ethanol-containing medium are determined.

PMID- 7728274
TI  - [The distribution of bacteria of the genus Bacillus into clusters by their
      spectrum of antagonistic activity].
AB  - The antagonistic activity of Bacillus strains against a lot of the pathogenic
      test-cultures was determined. It was established that strains-antagonists might
      be divided into several groups with a range of the most susceptible test-cultures
      typical of each group. The method of the rapid screening of strains-antagonists
      with the desirable antagonistic quality was suggested.

PMID- 7728275
TI  - [The reaction of Escherichia coli cells to an acid nonnutritive medium].
AB  - Cells of Escherichia coli K 12 grown on nutritious broth and twice washed off
      from medium by 90 mM solution of lithium chloride alkalize to some degree acidic
      non-nutritional medium. Registration of rates of alkalization by the cells at
      constant pH (from 3.0 to 5.5) was made by means of automatic potentiometric
      titration. The initial rate of alkalization was higher at low pH of the
      incubation medium. Different mechanisms of medium alkalization by bacterial cells
      (consumption of protons by cells, antiport proton/metal ion and release of basic
      products by cells) are discussed.

PMID- 7728276
TI  - [The characteristics of pneumococcal contamination of the respiratory tract in
      healthy and sick children].
AB  - The results of six-year-long investigations of microbiological indices of
      pneumococcal microflora in healthy carriers and in children with chronic
      respiratory pathology are presented in the paper. Peculiarities of pneumococcal
      contamination of nasopharynx mucosa in the both groups were detected. A
      difference in the intensity of pneumococcus colonization and localization in
      upper respiratory tract between healthy and sick children was found. Data on
      adhesive and lysozyme activity of the obtained stocks as factors favourable for
      microflora contamination and persistence on nasopharynx mucosa are given. An
      analysis of antibiograms of the obtained pneumococcus cultures was performed. The
      recent trend of preservation of pneumococcus sensitivity to the main groups of
      commonly used antibiotic preparations has been affirmed.

PMID- 7728277
TI  - [A new preparation of biosporin and its effect on the intestinal microflora in
      dysbacterioses in newborn infants].
AB  - Biosporin, a new biological drug made on the basis of sporulating aerobic
      bacteria, has been studied for its effect on the intestine microflora in case of
      dysbacterioses and acute digestive disorders in 53 newborn children with
      perinatal pathology. The results obtained prove high prophylactic and therapeutic
      efficiency (clinical and bacteriological) of biosporin for dysbacterioses and
      diarrheas in the newborn children. No negative after effects were observed. The
      preparation not only decontaminated pathogenic microorganisms, but also promoted
      necessary correction bacteriotherapy.

PMID- 7728278
TI  - [The decontamination of microorganisms in potable water by using ultraviolet
      radiation].
AB  - The inactivation of Escherichia coli, Streptococcus faecalis, Proteus vulgaris,
      Pseudomonas aeruginosa and Bacillus subtilis by UV radiation in batch and flow
      through systems and influence of different factors on inactivation have been
      studied. The necessary required disinfection doses were defined and compared with
      the data of other authors.

PMID- 7728279
TI  - [The destruction of mono- and polycyclic aromatic hydrocarbons by cultures of
      Pseudomonas fluorescens 1-D biovar II and Bacillus subtilis 2-D].
AB  - Cenosis of microorganisms, coal resin destructors, is selected by the percolation
      method. A microbiological analysis of bacterial associations able to destruction
      of aromatic hydrocarbons composing the coal resin is carried out. Pure cultures
      are isolated as the most active destructors of these substrates. Destructive
      cultures are identified as Pseudomonas fluorescens 1-D biovar II and Bacillus
      subtilis 2-D. Efficiency of the microbiological refinement of coal-resin
      contaminated soil by the isolated pure cultures and by their mixture is compared
      with self-refinement of soil. It is shown that complete refinement of soil from
      coal resin with contamination of 1 g per 1 kg of soil was attained after 160 days
      using the mixture of isolated destructive cultures P. fluorescens 1-D biovar II
      and B. subtilis 2-D. Usage of only P. fluorescens 1-D biovar II provided
      destruction of 87% of contaminating substances for the same period, whereas self
      purification of soil by the natural cenosis of microorganisms made the
      purification level of 42%.

PMID- 7728280
TI  - Education and change in cognitive function. The Epidemiologic Catchment Area
      Study.
AB  - The association between educational attainment and decline in cognitive function
      over an interval of 1 year was examined for 14,883 subjects 18 years and older in
      the National Institute of Mental Health Epidemiologic Catchment Area Study.
      Cognitive function was assessed at both time points by the Mini-Mental State
      Examination (MMSE); cognitive decline was coded as a dichotomous variable and was
      defined as 1 if the subject's score had declined 3 or more points from the
      baseline MMSE score at the 1-year follow-up interview and as 0 otherwise. The
      association between educational attainment and decline in cognitive function over
      1 year was examined in logistic regression models that were stratified by age
      group (< 65 years, > or = 65 years) and by baseline MMSE level (MMSE > 23, MMSE <
      or = 23). Covariates included age, baseline MMSE score, ethnicity, residence,
      lifetime diagnosis of abuse of alcohol or other drugs, and gender. In those with
      baseline MMSE > 23, education was a significant predictor of cognitive decline,
      not only in the elderly but also in younger subjects. Among those with baseline
      MMSE < or = 23, education was not a significant predictor of cognitive decline.
      The fact that education provides protection against cognitive decline even in
      those younger than 65 years, in whom the prevalence and incidence of dementia are
      very low, would seem to indicate that education or its correlates provides
      protection against processes other than dementia that might produce a decline in
      test performance in young persons.

PMID- 7728281
TI  - An investigation of the association between exposure to styrene and hearing loss.
AB  - The importance of the association between advancing age and hearing loss is well
      recognized. Further, prolonged significant noise exposures are also known to
      result in permanent hearing loss. However, little is known of the contribution of
      industrial chemical exposures to hearing loss. Information available, from both
      animal and human studies, raises the possibility that certain aromatic
      hydrocarbons are ototoxic. The purpose of this study was to assess whether
      occupational styrene exposure causes hearing loss in a group of workers in the
      fiber-reinforced plastics manufacturing industry. The hearing acuity of 299
      subjects was determined, using pure-tone screening audiometry, at the beginning
      of a single workshift and again at the end of the shift. On the same day, the
      personal, time-weighted average exposures of each subject to both styrene and
      noise were measured. In addition, information on the following factors was
      obtained from each participant: previous work history, including exposures to
      noise and chemicals; use of personal protective equipment for noise or solvents;
      personal and family history of hearing problems; and smoking history. Current
      exposures together with work histories were used to construct lifetime noise and
      styrene exposure indices. No conclusive evidence was found for a chronic styrene
      induced effect on hearing acuity, when both noise and styrene lifetime exposures
      were taken into account. As expected, age and noise exposures were highly
      important variables, both positively associated with hearing loss. In addition,
      the detrimental effect of noise exposure on hearing acuity was found to be
      strengthened with increased age. Noise and styrene exposures were highly
      correlated, clearly illustrating the importance of considering all associated
      variables in analysis of such data. No evidence was found for a relationship
      between smoking, recreational noise, solvent exposures, and hearing loss.

PMID- 7728282
TI  - Long-term survival after coronary heart disease. Comparisons between men and
      women in a national sample.
AB  - This study examined the sex differential in long-term survival after incident
      coronary heart disease (CHD) in the Epidemiologic Followup Study to the First
      National Health and Nutrition Examination Survey. This cohort was first contacted
      in 1971 to 1975 with follow-up through 1987. Of the 1407 white participants for
      whom CHD was identified at some point during the study, 56% of men and 46% of
      women died during the follow-up period. After adjustment for age at incidence,
      traditional heart disease risk factors, and initial coronary disease diagnosis,
      the relative risk of death among women compared to men was 0.70. Women's survival
      advantage after myocardial infarction was 0.81. Women who had ever taken post
      menopausal estrogens were most likely to survive after CHD or myocardial
      infarction compared to men (relative risks [RRs] = 0.42 and 0.57, respectively),
      although women who did not take estrogen were also significantly more likely than
      men to survive after CHD (RR = 0.79) but not after myocardial infarction (RR =
      0.88).

PMID- 7728284
TI  - Red blood cell sodium and potassium concentration and blood pressure. The Gubbio
      Population Study.
AB  - The relations of red blood cell sodium (RBC Na) and potassium (RBC K)
      concentrations to blood pressure and prevalence of hypertension were assessed for
      1805 men and women, aged 25 to 74 years, who participated in the baseline
      examination of the Gubbio Population Study in north central Italy. In men, in
      univariate analyses, RBC Na concentration was not significantly related to
      systolic or diastolic blood pressure, while RBC K concentration was significantly
      and inversely related to blood pressure. In women RBC Na values correlated
      significantly and directly with systolic and diastolic pressure, but RBC K
      concentration was not significantly related to blood pressure. Results of the
      multivariate analyses indicated in men a significant independent and inverse
      relationship of RBC K concentration with hypertension and blood pressure, and in
      women a significant positive association of RBC Na concentration with
      hypertension. RBC Na did not relate independently to either systolic or diastolic
      blood pressure in men or women. Age-specific analyses suggested that the
      relationships between RBC K level and blood pressure in men and the relationship
      between RBC Na level and hypertension in women were stronger in older (age 55 to
      74 years) compared to younger participants (25 to 54 years). These findings
      indicate that the associations of RBC Na and K concentrations and hypertension
      may be sex and age specific. The nature of these gender- and age-specific
      associations remains to be clarified. Prospective data are also needed for
      further clarification of the relation of intracellular Na metabolism to the
      etiology of hypertension.

PMID- 7728283
TI  - Incidence and predictors of diabetes in Japanese-American men. The Honolulu Heart
      Program.
AB  - Reports on the incidence and predictors of diabetes in minority populations are
      infrequent. The 6-year cumulative incidence of diabetes between 1965 and 1974 was
      estimated among 7210 Japanese-American men aged 45 to 68 years who were enrolled
      in the Honolulu Heart Program and were free of clinically recognized diabetes at
      baseline. The incidence of "possible" diabetes (based on history, medication, or
      hospital diagnosis) was 12.8% and the incidence of "probable" diabetes (based on
      diabetic medication) was 5.7%. Estimates of incidence in subjects with a
      nonfasting glucose concentration less than 225 mg/dL 1 hour after a 50-g load
      were 9.7 and 4.0%, respectively. Multivariate adjusted odds ratios (ORs) for
      probable diabetes in all subjects comparing the upper quintile with the lower
      four quintiles combined for continuous variables indicated statistically
      significant direct associations with body mass index (OR, 1.69; 95% confidence
      interval (CI), 1.31 to 2.18), 1-hour postchallenge glucose level (OR, 5.79; 95%
      CI, 4.58 to 7.33), triglyceride levels (OR, 1.47; 95% CI, 1.14 to 1.91), systolic
      blood pressure (OR, 1.36; 95% CI, 1.05 to 1.76), and parental history of diabetes
      (OR, 1.73; 95% CI, 1.29 to 2.33), and an inverse association with physical
      activity (OR, 0.49; 95% CI, 0.34 to 0.72), using logistic regression models
      including these variables as well as age, subscapular/triceps skinfold ratio, and
      hematocrit simultaneously. Associations were similar but slightly weaker in men
      with glucose levels less than 225 mg/dL and in those who remained free of
      cardiovascular disease. When older men (55 to 68 years old) were compared with
      younger (45 to 54 years old) men, associations among the older group were
      stronger for body mass index, physical activity, and systolic blood pressure and
      they were weaker for glucose levels, triglyceride values, and parental diabetes.
      Results suggest that body mass index, physical inactivity, glucose level, and
      parental diabetes appear to be independent risk factors for diabetes, while
      triglyceride and systolic blood pressure levels may be markers for an adverse
      cardiovascular risk factor profile associated with diabetes and may reflect an
      insulin resistance syndrome.

PMID- 7728285
TI  - Effect of vitamin C supplementation on lipoprotein cholesterol, apolipoprotein,
      and triglyceride concentrations.
AB  - Plasma ascorbic acid (AA) frequently is positively correlated with high-density
      lipoprotein (HDL) cholesterol and inversely related to total cholesterol
      concentration. To determine if vitamin C intake can alter cholesterol
      concentration, we examined the effect of vitamin C supplementation (1 g/d) on
      lipoprotein cholesterol and triglyceride levels in 138 subjects, aged 20 to 65
      years, who completed an 8-month randomized, double-blinded, placebo-controlled
      trial. Individuals with higher levels of plasma AA (> 80 mumol/L for men and > 90
      mumol/L for women), HDL cholesterol (> 1.4 mmol/L for men and > 1.7 mmol/L for
      women), and total cholesterol (> 6.7 mmol/L) were excluded from this trial. We
      observed no overall effect of supplementation on plasma concentrations of HDL,
      LDL, or total cholesterol, apolipoprotein (apo) B, or triglyceride. We did
      observe a marginally significant (P < 0.10) increase of 1.9 mumol/L (5.3 mg/dL)
      in apo A-I concentration with supplementation and a significant (P < 0.05)
      difference of 0.10 mmol/L (3.8 mg/dL) in HDL cholesterol concentration between
      vitamin C and placebo treatment in a nonrandomized subgroup of individuals (n =
      43) and a baseline plasma AA level less than 55 mumol/L. Although the apo A-I
      concentration increase was only marginally significant with supplementation,
      change in plasma AA concentration was significantly (P < 0.05) correlated with
      change in apo A-I concentration in the entire sample. The overall results of this
      trial were negative, but our data do not allow us to rule out the possibility
      that vitamin C supplementation might increase HDL cholesterol or apo A-I
      concentrations among individuals with lower plasma AA levels.

PMID- 7728286
TI  - Comparing standardized mortality ratios.
AB  - It is well known that the ratio of two standardized mortality ratios (SMRs) is
      not in general an unbiased estimate of the underlying within-stratum ratio of
      rates of one subcohort relative to another. It is also established, although less
      well known, that a sufficient condition for unbiasedness is that the underlying
      stratum-specific rates in each of the two subcohorts be proportional to the
      reference population. Further, the ratio of SMRs is more precise than the wholly
      internal (Poisson regression) estimate of rate ratio. In data that are compatible
      with the proportionality assumption, use of the ratio of SMRs thus buys precision
      at the cost of increased vulnerability to bias. To further elucidate choice
      between methods, we derive expressions for the asymptotic precision of each.
      These show that improved precision of ratio of SMRs depends on the extent to
      which the distribution of expected deaths over strata is different in the two
      cohorts, or equivalently, on the variance over strata of the proportion of
      expected deaths falling in the first cohort. The results are illustrated by
      hypothetic examples.

PMID- 7728287
TI  - Repeatability of nutrient intakes estimated by a semiquantitative food frequency
      questionnaire in elderly subjects.
AB  - In order to evaluate the repeatability of nutrient values estimated from a
      semiquantitative food frequency questionnaire being used in a longitudinal study
      of the relationships between diet, hemostatic factors, and stroke risk in the
      elderly in Western Sydney, a subsample of 62 participants (24 men, 38 women)
      completed a repeat questionnaire approximately 1 month after baseline data were
      collected. The mean age was 78 years (range, 65 to 88; median, 78). Nutrient
      values calculated from the repeat questionnaire were not significantly different
      from the baseline results by paired t test. Intraclass correlation coefficients
      ranged from 0.63 for beta carotene to 0.82 for saturated fat. Quadratic weighted
      kappa values were calculated for quintile categories and these ranged from 0.50
      for fiber to 0.86 for ethanol. These values are comparable to previously
      published results in elderly subjects and confirm that repeatability of nutrient
      intakes estimated using semiquantitative food frequency questionnaires is very
      high in the elderly. Older subjects may be more established in their dietary
      habits than younger subjects, so any tendency for repeatability to decrease due
      to impaired memory associated with advanced age is offset by a lower
      intraindividual variability in dietary habit.

PMID- 7728288
TI  - Reproducibility of an Italian food frequency questionnaire for cancer studies.
      Results for specific nutrients.
AB  - The reproducibility of measures of the intake of total energy and 27 selected
      nutrients from a quantitative food frequency questionnaire (FFQ) used in a case
      control study on cancer of the breast, ovary, and digestive tract was evaluated.
      The results of two FFQ administrations at an interval of 3 to 10 months (median =
      5.4 months) to 452 volunteers (144 males and 308 females; median age = 50 years)
      from three Italian provinces (Pordenone, Genoa, and Fori) were compared. Pearson
      correlation coefficients (r) between crude nutrient intake (unadjusted for
      energy) ranged from 0.50 for vegetable fat to 0.80 for alcohol, with most values
      falling between 0.60 and 0.70 (median r = 0.67). Adjustment of nutrient intakes
      for total energy slightly decreased most coefficients (median r = 0.60). The
      agreement between the two measurements did not differ substantially by sex, age,
      education, and interval between interviews. The contribution of specific FFQ
      components (i.e., frequency-only questions, open questions, portion size, and fat
      intake pattern) was also assessed separately with respect to the performance and
      reproducibility of nutrient measures, yielding, in general, very similar results.
      The seven questions concerning individual fat intake pattern, which were used to
      modulate the composition of various recipes, led, however, to a significant
      increase in mean daily intake of vegetable fat, oleic acid, and vitamin E, but a
      reduction of estimated daily intake of linoleic acid and polyunsaturated fatty
      acids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728289
TI  - How does education affect cognitive function?

PMID- 7728290
TI  - The complexity of studying coronary heart disease in women.

PMID- 7728291
TI  - Age-related hearing loss and bone mass in a population of rural women aged 60 to
      85 years.
AB  - Demineralization of the cochlear capsule in conjunction with age-related bone
      mass loss may be one biologic factor contributing to hearing loss in the elderly.
      In other metabolic bone diseases, including Paget's disease of the bone and
      cochlear otosclerosis, demineralization of the cochlea has been associated with
      sensorineural hearing loss. In 1988/1989, the relation between hearing loss and
      bone mass of the radius and femoral neck was studied cross-sectionally in 369
      women aged 60 to 85 years from three rural communities. Hearing sensitivity was
      measured using audiometry, and bone mineral density of the radius and femoral
      neck was measured using single- and dual-photon densitometry, respectively. Three
      variables, ascertained by interview, were associated with an increased odds for
      hearing loss: age, family history of hearing loss before the age of 50 years, and
      current use of more than two nonestrogen, nonthiazide prescription medications.
      After consideration of the effect of these three variables, women with femoral
      neck bone mass values below the mean value of 0.696 g/cm2 for this population had
      a 1.9 greater odds of having a hearing loss (confidence interval: 1.30, 2.50).
      This study demonstrated a consistent adjusted association between femoral neck
      bone mass and age-related hearing loss in a population of rural women aged 60 to
      85 years. No consistent association was observed between radial bone mass and
      hearing loss.

PMID- 7728292
TI  - Improved survival of hospitalized patients with acute myocardial infarction from
      1981-1983 to 1992 in Israel. The SPRINT Study Group and The Israeli Thrombolytic
      Survey Group. Secondary Prevention Israeli Nifedipine Trial.
AB  - BACKGROUND: This study compares in-hospital and 1-year mortality rates in two
      large cohorts of patients with acute myocardial infarction (AMI) who were
      admitted to coronary care units in Israel in 1981-1983 and in 1992. Since the
      late 1960s and early 1970s there has been a remarkable decline in mortality from
      cardiovascular causes in most Western countries; the reason for this decline is
      not completely understood. Although several studies have shown a significant
      decrease in in-hospital mortality from AMI between the 1960s and the 1980s,
      studies comparing survival after AMI between the 1980s and 1990s are relatively
      scarce. Over the past decade important medical treatments and procedures for the
      management of AMI were introduced. METHODS: Between August 1981 and July 1983,
      5839 consecutive patients were admitted to 13 coronary care units in Israel with
      a confirmed diagnosis of AMI. Demographic and medical data from hospital charts
      were recorded. Mortality follow-up was complete for 99% of hospital survivors for
      a mean period of 10 years. A second cohort of 623 consecutive patients with AMI
      hospitalized during January and February of 1992 in the same 13 coronary care
      units were followed up for 1 year after discharge. RESULTS: Sex distribution and
      mean age were very similar in the two cohorts. Unadjusted in-hospital mortality
      was 18% in 1981-1983 versus 11% in 1992 (P < 0.001). After multiple regression
      analysis, the in-hospital mortality odds (adjusted for age, sex and history of
      previous infarction) declined from 1981-1983 to 1992 by 22-67%. The reduction in
      in-hospital mortality rates from 1981-1983 to 1992 was more pronounced among
      patients aged over 65 years. One-year survival was 91% and 92% in patients
      discharged in 1981-1983 and 1992, respectively; however, 1-year after discharge,
      the survival rate for patients older than 65 years was 85% in 1981-1983 versus
      89% in 1992. None of the 5839 patients hospitalized in 1981-1983 received
      thrombolytic treatment or mechanical revascularization, whereas 46% and 9% of
      patients received these respective treatments in 1992. CONCLUSIONS: This study
      suggests that, over the past decade, changes in medical treatment, thrombolytic
      therapy and mechanical revascularization have significantly contributed to the
      improvement of the immediate prognosis of patients hospitalized as a result of
      AMI.

PMID- 7728293
TI  - Risk of subsequent cardiac events in stable convalescing patients after first non
      Q-wave and Q-wave myocardial infarction: the limited role of non-invasive
      testing. The Multicenter Myocardial Ischemia Research Group.
AB  - BACKGROUND: Patients recovering from myocardial infarction are frequently
      evaluated by non-invasive tests for evidence of myocardial ischemia before
      returning to work or full activity. The purpose of this study was to evaluate the
      prognostic significance of clinical and non-invasive ischemic test variables
      assessed in 549 stable, convalescing patients (median 2 months) after their first
      Q-wave (n = 363) and non-Q-wave (n = 186) myocardial infarction. METHODS: The
      ischemic tests performed were resting ECG, exercise ECG, ambulatory ECG, and
      stress thallium scintigraphy. RESULTS: Cardiac events (unstable angina requiring
      hospitalization, non-fatal reinfarction, or death from cardiac causes) were
      observed during a mean 23-month follow-up in 57 patients (15.7%) with Q-wave and
      in 31 of patients (16.7%) with non-Q-wave infarction. In a step-wise Cox
      regression model, the only significant independent predictors of subsequent
      cardiac events (P < 0.001) were post-infarction angina and insulin-dependent
      diabetes mellitus. The type of infarction did not make a significant contribution
      to the risk of cardiac events (P = 0.29). However, an interaction between infarct
      type and post-infarction angina was of borderline significance (P = 0.065), with
      angina associated with more cardiac events in patients with non-Q-wave than in
      those with Q-wave infarction. None of the ischemic tests contributed
      significantly to the Cox model in predicting cardiac events in either infarct
      type. CONCLUSION: Stable convalescing patients who have recovered from first Q
      wave and non-Q-wave myocardial infarction have similar long-term prognoses. The
      occurrence of post-infarction angina is associated with increased risk of cardiac
      events in patients with both infarct types, with more marked effect in non-Q-wave
      than Q-wave infarctions. Ischemia detected by non-invasive tests performed in the
      convalescing phase after myocardial infarction was not prognostically useful in
      either infarct type.

PMID- 7728294
TI  - Bibliography of the current world literature.

PMID- 7728295
TI  - Clinical significance of right ventricular dilatation in patients with right
      ventricular infarction.
AB  - BACKGROUND: Right ventricular infarction can be accurately diagnosed by ST
      segment elevation in the right precordial leads. However, the clinical outcome of
      right ventricular infarction encompasses a wide spectrum, ranging from no
      hemodynamic compromise to cardiogenic shock. The present study examined the
      clinical significance of echocardiographic right ventricular dilatation in
      patients with right ventricular infarction. METHODS: We studied 60 consecutive
      patients with ECG evidence of right ventricular infarction (at least 1 mm ST
      segment elevation and QS or QR in V4R) after their first acute Q-wave inferior
      infarction. They had been admitted to the coronary care unit within 24 h of the
      onset of chest pain. The presence of right ventricular dilatation was diagnosed
      when the end-diastolic ratio between right and left ventricle was more than 0.5
      on two-dimensional echocardiogram. RESULTS: Of the 60 patients with ECG evidence
      of right ventricular infarction, 29 had right ventricular dilatation (group 1)
      and 31 did not (group 2). We used four clinical variables in multivariate
      analysis to determine the significant factors related to right ventricular
      infarction. Mean right atrial pressure and number of left ventricular segments
      with advanced asynergy were found to be the important factors. Furthermore, a
      significantly higher incidence of major complications (cardiogenic shock and need
      for temporary pacing) was observed in group 1 than in group 2. Right ventricular
      dilatation was found to be the significant factor related to major complications.
      CONCLUSION: Echocardiographic right ventricular dilatation is an important non
      invasive sign obtained on admission in patients with right ventricular
      infarction, because it is associated with larger left ventricular infarct size
      and increased risk of major complications.

PMID- 7728296
TI  - Direct relationship between ischaemic burden and myocardial release of products
      of lipid peroxidation in patients undergoing percutaneous transluminal coronary
      angioplasty.
AB  - BACKGROUND: Recent studies have shown that free radical activity is increased in
      humans during percutaneous transluminal coronary angioplasty. These studies,
      however, have failed to localize the site of free radical activity or to
      demonstrate a relationship between ischaemic burden and free radical production.
      METHODS: The relationship between ischaemic burden and subsequent lipid
      peroxidation was studied during 16 inflations in eight patients undergoing
      angioplasty to anterior descending artery lesions. Two inflations 15 min apart
      were studied in each patient, one using a conventional (occlusive) balloon and
      one using the ACS Rx 'perfusion' balloon. The severity of the ischaemic insult
      associated with each inflation was assessed by contrast ventriculography, change
      in left ventricular end-diastolic pressure and myocardial lactate release 30 s
      after balloon deflation. Plasma levels of lipid peroxidation products were
      assessed by analysis of thiobarbituric-acid-reactive substances. RESULTS: A
      direct relationship was observed between the ischaemic burden and the myocardial
      release of lipid peroxidation products over the first 4 min after balloon
      deflation (F = 5.6; P < 0.006). In each patient, one of the inflations was
      associated with a greater degree of ischaemia. Left ventricular ejection fraction
      was lower (P < 0.001) and left ventricular end-diastolic pressure was higher (P <
      0.002) during the 'ischaemic' inflations. Myocardial release of lipid
      peroxidation products was significantly higher after the 'ischaemic' balloon
      inflation (F = 7.65; P < 0.009). CONCLUSION: Brief periods of human myocardial
      ischaemia result in myocardial release of lipid peroxidation products in direct
      proportion to the severity of the preceding ischaemic insult.

PMID- 7728297
TI  - In-vitro effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors on non-hepatic LDL receptor activity: evidence of lack of stimulatory
      effect of pravastatin.
AB  - BACKGROUND: It is speculated that, as a result of its tissue selectivity,
      pravastatin may be a safer drug than the lipophilic 3-hydroxy-3-methylglutaryl
      Coenzyme A (HMG-CoA) reductase inhibitors in combination therapy involving drugs
      with potential muscle toxicity. Several studies have shown specific inhibitory
      activity on hepatic cholesterogenesis and a potent induction of hepatic low
      density lipoprotein (LDL) receptors. However, data about its effect on
      stimulation of LDL receptor activity on non-hepatic cells are not available.
      METHODS: Several experiments were carried out in order to assess the in-vitro
      effect of HMG-CoA reductase inhibitors on the activity of LDL receptors of human
      non-hepatic cells. Lymphocytes from both normolipidemic controls and patients
      with heterozygous familial hypercholesterolemia along with human fibroblasts were
      cultured in both the presence and absence of pravastatin and lovastatin. RESULTS:
      Pravastatin, at concentrations of 0.25-50 mumol/l, did not enhance the LDL
      receptor activity of lymphocytes derived from both patients with familial
      hypercholesterolemia and normolipidemic controls. In contrast, lovastatin, at
      concentrations of 0.25 mumol/l, increased the LDL receptor activity in both
      control lymphocytes and lymphocytes from patients with familial
      hypercholesterolemia by 121% and 148%, respectively. Fibroblast LDL receptor
      activity was not altered by pravastatin at a concentration of 50 mumol/l, whereas
      lovastatin at the same concentration increased the LDL uptake by 153%.
      CONCLUSION: From in-vitro experiments of LDL receptor activity stimulation, we
      conclude that pravastatin has little effect on non-hepatic cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7728298
TI  - Coronary vasoconstriction in response to acetylcholine after balloon angioplasty:
      possible role of endothelial dysfunction.
AB  - BACKGROUND: Abnormal endothelium-dependent vasomotion has frequently been
      observed early after coronary angioplasty. The aim of this study was to
      investigate endothelium-mediated coronary vasomotion caused by increasing
      intracoronary infusions of acetylcholine into epicardial coronary arteries 3-6
      months after coronary angioplasty in patients without restenosis (50% luminal
      diameter reduction). METHODS: Intracoronary acetylcholine was infused during
      follow-up coronary angiography followed by an intracoronary bolus of 250 g
      nitroglycerin in 18 patients who had undergone successful angioplasty of 21
      isolated coronary artery lesions. Using an automated edge-detection program,
      coronary artery measurements were performed in the proximal reference segment, in
      the proximal part of the angioplasty site, at the site of previous maximal
      stenosis, in the distal part of the angioplasty site, and in the distal reference
      segment. RESULTS: In the segments of the coronary artery not manipulated by
      balloon catheter, acetylcholine did not produce significant luminal diameter
      changes (+2 +/- 23% in the proximal segment and -3 +/- 27% in the distal segment
      at 10(-4) mol/l). All the angioplasty vessel segments, excluding the proximal
      reference segments, showed an abnormal dose-related reactivity to the
      acetylcholine. Maximal vasoconstriction was observed at 10(-4) mol/l and was 4.9
      +/- 11.1% in the proximal reference segment, 9.3 +/- 19.1% in the proximal
      angioplasty site (P = 0.0314), 20.3 +/- 24.1% at the site of previous maximal
      stenosis (P = 0.0005), 10.7 +/- 16.8% at the distal angioplasty site (P =
      0.0098), and 9.3 +/- 14.1% in the distal reference segment (P = 0.0032). The
      maximal response of the angioplasty site to acetylcholine and to nitroglycerin
      did not correlate either with the time to follow-up or with the follow-up
      stenosis. Nitroglycerin-induced vasodilation was significant in all segments, but
      was lower in the lesion-related segments. Acetylcholine evoked the same effect on
      both the vessels that were manipulated and those that were not. CONCLUSIONS:
      Three to 6 months after coronary angioplasty, endothelium-dependent vasodilation
      was impaired not only at the site of previous maximal stenosis, but also in
      segments directly injured by balloon inflation. In contrast, endothelium
      independent vasodilation by nitroglycerin is maintained in all segments. These
      observations suggest that the endothelium is still functionally impaired in the
      area of balloon dilation.

PMID- 7728299
TI  - Effects of intracoronary infusion of atrial natriuretic peptide on pacing-induced
      myocardial ischemia in patients with effort angina pectoris.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP) has been shown to dilate the
      coronary artery. The aim of this study was to determine whether, in patients with
      effort angina pectoris, intracoronary infusion of ANP attenuates pacing-induced
      myocardial ischemia either by dilating the stenotic lesion in a large coronary
      artery or by dilating collateral vessels. METHODS: We studied six patients who
      had total or subtotal occlusion in one coronary artery and well-developed,
      angiographically visible collateral vessels (group A) and five patients who had a
      significant stenosis in a large coronary artery with no visible collateral
      vessels (group B). Their heart rate was increased by atrial pacing both before
      and after intracoronary infusion of ANP (0.03 microgram/kg/min for 15 min) into
      the donor artery of collateral vessels in group A or into the stenotic artery in
      group B. RESULTS: Before ANP infusion, all patients of both groups developed an
      ischemic ST-segment depression (> or = 0.1 mV) and angina-like chest pain from
      pacing tachycardia. After ANP infusion, significant ST-segment depression was
      induced by rapid pacing in only one out of six patients of group A, whereas it
      was noted in all patients of group B (P < 0.01). After ANP infusion, chest pain
      developed in one out of six patients in group A, whereas it appeared in four out
      of five patients in group B (P < 0.05). ANP significantly dilated the
      angiographically normal segment of the epicardial coronary artery, but it did not
      significantly change the severity of the stenotic lesion in either group. ANP did
      not change the basal arterial pressure or heart rate, nor did it change their
      response to pacing tachycardia. CONCLUSION: Infusing ANP into the donor artery of
      collateral vessels, but not into the artery with culprit stenotic lesion,
      attenuated pacing-induced myocardial ischemia. Therefore, the beneficial effects
      of ANP in reducing pacing-induced myocardial ischemia may result from the
      increase in myocardial perfusion to the ischemic area caused by dilating the
      collateral vessels.

PMID- 7728300
TI  - The surgical management of congenital coronary artery fistula.
AB  - BACKGROUND: Congenital coronary artery fistula (CAF) is a very rare
      cardiovascular anomaly and only 400 cases have been reported. The purpose of this
      study was to analyse the experience of surgical treatments in CAF and evaluate
      the surgical indications, techniques and long-term results. METHODS: A
      retrospective study reviewing 20,000 cardiovascular surgical cases from 1978 to
      1993 was carried out, from which 14 patients with CAF were identified and
      diagnosis was confirmed by both coronary angiography (CAG) and echocardiography.
      Twelve patients had heart-related symptoms. CAG revealed that fistulous channels
      arose from the right coronary artery (RCA) in seven patients, and from the left
      coronary artery (LCA) in six patients. One patient had multiple fistulae, from
      both RCA and LCA. The surgical managements and late follow-up were assessed.
      RESULTS: Surgery was performed on 13 patients; one had died before surgery.
      Cardiopulmonary bypass (CPB) was performed in 11 patients. The presence of
      coronary aneurysm was treated by reduction plasty of the aneurysm (four
      patients). Other procedures were coronary artery bypass grafting (CABG; four
      patients), ventricular septal defect (VSD) and patent ductus arteriosus (PDA)
      closure (one patient), and one patient had mitral valve replacement. The mean
      follow-up time was 7.2 years and all symptomatic patients improved their New York
      Heart Association (NYHA) functional class (average 1.2 classes). Although there
      were no surgical deaths in our group, one late death (6 months after surgery) was
      caused by acute myocardial infarction; this resulted in an annual mortality rate
      of 1%. CONCLUSIONS: Surgical closure of CAF can be recommended because it is a
      low-risk procedure and leads to good long-term results. The problems with
      myocardial protection, residual fistula prevention and surgical techniques must
      be emphasized. For these purposes, special surgical techniques that have been
      introduced are described.

PMID- 7728301
TI  - Generation of therapeutic T-lymphocytes after in vivo tumor transfection with an
      allogeneic class I major histocompatibility complex gene.
AB  - In an effort to enhance the generation of tumor-reactive T-lymphocytes for
      adoptive immunotherapy, we examined the effects of in vivo transfection of an
      allogeneic major histocompatibility complex (MHC) class I gene (H-2Ks) of the
      poorly immunogenic B16BL6 (BL6) melanoma of H-2b origin. Cells from lymph nodes
      (LNs) draining these tumors after transfection were assessed in adoptive
      immunotherapy experiments for tumor reactivity after sequential activation with
      anti-CD3 monoclonal antibody (mAb) followed by culture in interleukin (IL)-2. H
      2Ks lipofection of progressively growing BL6 subcutaneous tumors did not reduce
      tumorigenicity. However, in vivo lipofection of BL6 by intratumor inoculation or
      admixture of H-2Ks cDNA/liposome complexes and tumor cells prior to inoculation
      resulted in enhanced development of sensitized T-lymphocytes in the draining LN,
      which mediated the reduction of the numbers of established 3-day parental lung
      metastases in six of six experiments. In subsequent studies, in vivo transfection
      of BL6 with naked H-2Ks cDNA was found to be more effective than lipofection in
      eliciting sensitized T-cells in the draining LN. Admixture of liposomes alone or
      control plasmid DNA did not have an adjuvant effect similar to H-2Ks cDNA.
      Relative tumor transfection efficiency was assessed by an indirect assay with the
      chloramphenicol acetyltransferase (CAT) reporter gene. BL6 tumors were more
      efficiently transfected by intratumor inoculation with naked cDNA compared with
      lipofection. In summary, in vivo allogenization of the poorly immunogenic BL6
      tumor resulted in enhanced generation of therapeutic T-cells effective in the
      treatment of parental tumor.

PMID- 7728302
TI  - Human class II major histocompatibility complex gene transfer into murine
      neuroblastoma leads to loss of tumorigenicity, immunity against subsequent tumor
      challenge, and elimination of microscopic preestablished tumors.
AB  - Immunological recognition of transformed cells is critically important to limit
      tumor development and proliferation. Because established tumors have escaped
      immune recognition and elimination, novel strategies to enhance antitumor
      immunity have been developed. A unique approach has used the introduction of
      genes encoding major histocompatibility complex (MHC) antigens into tumor cells.
      Experiments in mice have shown that the expression of syngeneic class II MHC
      antigens in tumor cells completely abrogates tumorigenicity and induces tumor
      specific immunity. In this study we sought to determine whether a more effective
      antitumor immune response would be generated by introducing xenogeneic class II
      MHC genes into tumor cells. To address this question we used recombinant
      retroviruses to express human class II MHC genes in a highly malignant murine
      neuroblastoma cell line, Neuro-2a. We found that normal mice inoculated with
      Neuro-2a expressing the human class II MHC antigen did not develop tumors and
      were immune to subsequent challenge with unmodified Neuro-2a cells. In addition,
      mice bearing small established Neuro-2a tumors were cured by vaccination with
      Neuro-2a expressing human class II MHC. We hypothesize that a similar approach
      using retroviral-mediated transduction of class II MHC genes into human tumor
      cells may be an effective alternative to current cancer treatment.

PMID- 7728303
TI  - Hemodynamic evaluation of recombinant human tumor necrosis factor (TNF)-alpha,
      TNF-SAM2 and liposomal TNF-SAM2 in an anesthetized dog model.
AB  - We have evaluated the hemodynamic effects of systemically administered
      recombinant human tumor necrosis factor (TNF)-alpha, TNF-SAM2 and liposome-bound
      TNF-SAM2 in an anesthetized mongrel dog model. A dose of 10 micrograms TNF
      protein/kg of each formulation was injected in a peripheral vein and mean
      systemic arterial pressure (SAP), heart rate (HR) and cardiac output (CO) were
      measured. TNF-alpha induced a marked drop in SAP in all three dogs (mean decrease
      = 59.3 +/- 5.2 mm Hg; to 61.5% of baseline; p = 0.008); whereas TNF-SAM2 caused a
      smaller and transient drop in SAP in four dogs (mean decrease = 25.5 +/- 10.1 mm
      Hg; to 81.2% of baseline; p = 0.086). In three dogs administered liposome-bound
      TNF-SAM2, which retains antitumor activity in vivo, a net slight hypertensive
      phase and sustained elevated CO occurred, followed by a return to an essentially
      normotensive state (101.0% of baseline SAP). This model demonstrates that the
      principal acute systemic toxicity of TNF, i.e., hypotension, can be markedly
      attenuated by liposomal formulation of a second-generation TNF.

PMID- 7728304
TI  - Helper T cells infiltrating human renal cell carcinomas have the phenotype of
      activated memory-like T lymphocytes.
AB  - Human renal cell carcinomas are characterized by an inflammatory infiltrate
      containing many T lymphocytes. Attempts to grow T cells from such tumors by
      culture in interleukin (IL)-2 have yielded heterogeneous populations of cells
      with functional characteristics typical of lymphokine-activated killer cells
      obtained by similar culture of cells from peripheral blood mononuclear cells. We
      examined a panel of surface markers expressed on T lymphocytes to determine if
      the CD4+ T cells infiltrating human renal cell carcinomas are different from
      those in peripheral blood mononuclear cells. By flow cytometry analysis the CD4+
      T cells in a panel of freshly digested human renal cell carcinoma primary and
      metastatic tumors expressed the activation markers CD69 and HLA-DR and manifested
      an increase in CD45RO and a reciprocal decrease in CD45RA expression as compared
      with peripheral blood CD4+ T cells. This suggests that CD4+ T cells infiltrating
      renal cell carcinomas are activated and have encountered antigen. However, the
      expression of the IL-2R alpha chain (CD25) was not different in tumor
      infiltrating CD4+ T cells and peripheral blood CD4+ T cells, suggesting that T
      cells infiltrating human renal cell carcinomas may have a block in proliferative
      capacity. The general failure of cultured tumor-infiltrating lymphocyte (TIL)
      from renal cell carcinoma to demonstrate tumor-specific reactivity may be due to
      the failure of such cells to grow in IL-2.

PMID- 7728305
TI  - Immunologic effects of levamisole in mice and humans: evidence for augmented
      antibody response without modulation of cellular cytotoxicity.
AB  - Selected immunomodulatory effects of levamisole were studied in patients with
      asymptomatic metastatic colon cancer and in a preclinical model (CF1 female mice
      treated with methyl-azoxymethanol acetate) for colon tumors. In the patient
      population studied, there was no augmentation of cellular cytotoxicity or
      alteration in lymphocyte subpopulations that participate in these functions. An
      increase in Fc receptor binding on circulating monocytes was apparent at the 4
      week timepoint; however, a corresponding increase in antibody-dependent cellular
      cytotoxicity was observed in only one of the six patients studied. In most
      patients, cellular cytotoxicity diminished with time. No significant effects on
      cellular immunity or carcinogenesis were observed in our murine studies. However,
      treatment with levamisole did increase circulating immunoglobulin levels and IgM
      response in mice immunized with the T-dependent antigen keyhole limpet
      hemocyanin. This parameter was not tested in the human trial. Failure to
      demonstrate antitumor effects on cellular immunity by levamisole in both human
      and murine studies suggests that these effects, if they do exist, may involve
      immunological parameters that were not tested using our methods or that may not
      be apparent in patients with more advanced malignancy.

PMID- 7728306
TI  - A phase II trial of concomitant interferon-alpha-2b and granulocyte-macrophage
      colony-stimulating factor in patients with advanced renal cell carcinoma.
AB  - This study was undertaken to test the hypothesis that the combination of
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-alpha-2b
      (INF-alpha) would have a favorable clinical impact on patients with advanced
      renal cell carcinoma. Fifteen patients were treated with INF-alpha, 5 million
      U/m2 three times a week and GM-CSF 5 micrograms/kg, subcutaneously, daily.
      Patients received two consecutive 4-week cycles and then restaged. There were no
      complete responses, two of 15 partial responses (13%), and 13 of 15 had no
      response (87%). Biological effects (eosinophilia and leukocytosis) were
      characteristically observed. The therapy was well tolerated, and most side
      effects were attributable to INF-alpha. The study failed to show that the
      addition of GM-CSF to INF-alpha would increase the response rate in patients with
      metastatic renal cell carcinoma by enhancement of macrophage tumoricidal
      activity.

PMID- 7728307
TI  - Intensive regimen of cytokines with interleukin-2 and interferon alfa-2b in
      selected patients with metastatic renal carcinoma.
AB  - We conducted a Phase II trial using an intensive regimen combining interleukin-2
      (IL2), interferon-alfa-2b (IFN), and lymphokine-activated killer (LAK) cells. The
      aim of this study was to evaluate the toxicity and the efficacy of this
      combination in selected patients with metastatic renal cell carcinoma. Thirty-one
      assessable patients were treated with at least one cycle of a regimen consisting
      of 20 x 10(6) IU/day s.c. IFN for 5 days, followed 2 days later by i.v.
      injections of 24 x 10(6) IU/m2/day IL2 every 8 h together with i.v. bolus of 5 x
      10(6) IU/m2/day IFN every 8 h during 5 days. After a 6-day break, during which
      four leukophereses were performed, this i.v. combination was administered along
      with the LAK cell reinjections for a maximum of 5 days. Twenty-seven patients
      underwent the two parts of the first course of treatment; respectively, 42% and
      46% of the planned dose of IL2 and IFN were administered. Several severe
      toxicities were observed including two treatment-related deaths. Significant
      tumor responses were observed in seven patients, including two complete
      remissions. Two of these patients remain alive without evidence of disease 36 and
      40 months after treatment, respectively. This intensive regimen of IL2 together
      with IFN and LAK cells cannot be recommended even in selected patients with
      metastatic renal cell carcinoma. In addition, our results argue against the
      concept of a dose-response relationship in this setting.

PMID- 7728308
TI  - Initial assessment and management of the severely head-injured patient.
AB  - Head injuries account for a significant proportion of acute hospital admissions.
      The first few hours after a serious head injury are extremely important,
      particularly in terms of reducing possible secondary injuries. This article
      addresses the management problems in this group of patients during this initial
      critical period.

PMID- 7728309
TI  - An unusual presentation of aortic dissection.

PMID- 7728310
TI  - Appraisal of doctors in the NHS: merit awards and performance-related pay.

PMID- 7728311
TI  - The role of cholecystokinin in appetite control.

PMID- 7728312
TI  - Central venous catheter care.

PMID- 7728313
TI  - Multidose vials: potential disaster?

PMID- 7728314
TI  - Suppurative thrombophlebitis.

PMID- 7728315
TI  - Fractured hip in a patient with ankylosing spondylitis and pulmonary fibrosis.

PMID- 7728316
TI  - Short-term growth: past, present and future.

PMID- 7728317
TI  - Pamidronate for Paget's disease of the bone.

PMID- 7728318
TI  - Advances in hepatology--transplantation, prognosis and imaging.

PMID- 7728319
TI  - Secondary transfer of patients with fulminant hepatic failure.
AB  - The principles of stabilisation before and monitoring during transportation are
      well established in intensive care practice, but fulminant hepatic failure
      presents especial problems. Transfer of patients to specialist liver failure
      units needs to be carried out without interruption of therapy aimed at delaying
      the onset of cerebral oedema, sepsis and haemodynamic instability.

PMID- 7728320
TI  - Laparoscopy in the diagnosis of chronic liver disease.
AB  - Although laparoscopy has been in use for a substantial length of time, it remains
      a much underused tool in the diagnosis of chronic liver disease. The purpose of
      this review is to assess the present practice of laparoscopy in order to define
      its place as a diagnostic tool for the hepatologist.

PMID- 7728321
TI  - Endometrial resection.
AB  - Transcervical resection of the endometrium (TCRE) is a technique that has gained
      popularity in gynaecological practice as an alternative to hysterectomy for
      patients presenting with menstrual disturbances. The advantages of such a
      technique over traditional hysterectomy include shorter hospital stay, more rapid
      recovery allowing return to normal daily activity and reduced perioperative
      morbidity, with associated health and economic benefits.

PMID- 7728322
TI  - Current management of congenital diaphragmatic hernia.
AB  - Infants born with congenital diaphragmatic hernia have a high mortality which is
      essentially due to the associated lung hypoplasia. However, there have been
      several recent innovations, both in the surgical approach and in techniques of
      neonatal intensive care, which have improved the outlook for some of these
      critically ill infants.

PMID- 7728323
TI  - Neural transplantation into the CNS. Selected articles from the 1st American
      Society for Neural Transplantation meeting. Clearwater, Florida, May 5-7, 1994.

PMID- 7728324
TI  - Excitochemical-induced trophic bridging directs axonal growth of transplanted
      neurons to distal target.
AB  - Brain grafts directly placed in their target regions often lack proper
      connections and normal regulation. When brain grafts are placed in their
      ontogenetic normal area, the axonal outgrowth of grafts to distal target regions
      is a major obstacle. We previously demonstrated that directional axonal growth of
      grafts can be facilitated by laminin. In this study we demonstrated that
      excitochemicals induced trophic environment can be strategically used as a bridge
      to guide transplanted neurons to innervate a distal target of millimeter
      distance, and has a unique effect on fiber expansion in the target region. To
      distinguish dopamine (DA) growth from that of transplants, 6-hydroxydopamine was
      unilaterally injected into medial forebrain bundle to remove dopamine innervation
      to the striatum. Ibotenic acid (IB), kainic acid (KA), or phosphate buffer
      (vehicle) were microinjected through a glass-pipet to make a 7 mm long tract
      between the substantia nigra and the striatum in Sprague-Dawley rats. Gestational
      14-15 days brainstem slurry was transplanted either in the same or a separate
      tract into nigra at the bottom of the bridge. All transplants survived with
      abundant serotonin (5-HT) and DA neurons. Traceable DA fibers formed distinct
      bundles from grafts along the length of IB/KA tracts. Upon arrival at their major
      target regions, fibers from bundles were capable of leaving the tracts, and
      reinnervating the DA-vacated striatum. The 5-HT fibers formed bundles similar to
      DA fibers but left the tract earlier upon arrival at their major target the
      globus pallidus and when arriving at the striatum and cortex. Fibers from grafts
      with vehicle tracts grew randomly and not into the tract. These results indicate
      that the trophic effects of chemical lesioning serves as a remarkably effective
      axonal guidance for more than one type of fetal neuron to innervate distal brain
      regions. This method has great potential in directing fibers in many transplant
      models.

PMID- 7728325
TI  - Fetal Ammon's horn transplants improve acquisition of a radial arm maze and a low
      rate operant schedule in trimethyltin-treated rats.
AB  - The results of previous studies indicated that block grafts of fetal hippocampal
      tissue made into cavities produced by aspiration lesions of the hippocampus in
      rats given the neurotoxin trimethyltin (TMT) significantly worsened the TMT
      induced deficit in water maze acquisition. The purpose of the present study was
      to test the hypothesis that a procedure for transplantation that produced less
      destruction to the host brain and resulted in transplants with less mass might
      produce recovery in a spatial learning task in TMT-exposed rats. Acquisition of
      an externally cued (spatial) version of the radial arm maze (RAM), an internally
      cued version of the RAM, and of a differential reinforcement of low rate (DRL)
      operant schedule was assessed in normal rats, rats given TMT, and rats given TMT
      and stereotaxic implants of either fetal Ammon's horn or entorhinal cortex. The
      rats receiving Ammon's horn transplants made significantly fewer reentries into
      the baited arms in both maze configurations and fewer reentries into the
      nonbaited arms in the spatial RAM than rats in the TMT-only and TMT/entorhinal
      cortex transplant groups. The rats receiving transplants of Ammon's horn made
      significantly fewer responses and received more reinforcements during training on
      the DRL-20 schedule than rats receiving just TMT or rats receiving TMT and
      transplants of fetal entorhinal cortex. These results support the proposal that
      transplantation procedures that cause less damage to the host brain and result in
      transplants that do not occupy a large extent of the ventricular space increase
      the probability of behavioral recovery.

PMID- 7728326
TI  - Fetal neocortical transplants grafted into neocortical lesion cavities made in
      newborn rats: an analysis of transplant integration with the host brain.
AB  - Fetal neocortical transplants placed into frontal cortex aspiration lesion
      cavities in newborn rats have been shown to survive and exchange connections with
      the host brain. To further study the afferent innervation of such transplants,
      enzyme- and immunohistochemical techniques were employed to examine the
      distribution of cholinergic, catecholaminergic and serotonergic fibers within the
      transplants, and radiochemical enzyme assays and high performance liquid
      chromatography were used to determine the content of neurotransmitter markers for
      these same fiber systems. To examine functional integration of the transplanted
      neurons in terms of activation of molecular signaling systems, the graft
      recipient animals were exposed to a novel open field environment. This behavioral
      testing paradigm is known to induce c-fos mRNA and Fos protein within several
      areas of the normal brain, including the sensorimotor cortex. Subsequent
      detection of the induction of this particular immediate early gene (transcription
      as well as translation) in the grafts would gene (transcription as well as
      translation) in the grafts would accordingly indicate genomic activation and
      therefore functional integration at the level of molecular signaling systems. Our
      results showed that these global fiber systems are distributed evenly throughout
      the extent of three mo old neocortical grafts and that the content of transmitter
      related markers for these systems do not differ significantly from control
      cortex. Open field exposure of the grafted animals resulted in c-fos mRNA and Fos
      protein expression of cells distributed throughout the transplants. We conclude
      that the "global" fiber system innervation of neocortical transplants placed into
      newborn rats is similar to the innervation of normal cortex and that grafted
      neurons respond to host brain activation at the level of molecular signaling
      systems.

PMID- 7728327
TI  - Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys.
AB  - Parkinsonism has been reported to improve following transplantation of fetal
      mesencephalic tissue into the striatum of MPTP-exposed monkeys and humans and in
      patients with idiopathic Parkinson's disease. While there is good evidence for
      the survival of grafted tyrosine hydroxylase (TH)-positive cells in animal
      studies, it is not known whether they produce neuronal effects that account for
      behavioral improvement after transplantation or whether spontaneous or graft
      induced changes in the host striatum are at least partly responsible. Are
      neuronal synaptic connections and dopamine release necessary, or would "toenails
      and talcum powder" do the job equally well? We have addressed these questions by
      studying several types of implantation surgeries, including sham surgery, the
      implantation of cerebellar tissue, and the implantation of mesencephalic TH
      positive fetal tissue of various gestational ages into the striatum. Adult male
      African green monkeys received systemic MPTP administration (cumulative doses of
      2.0-2.5 mg/kg) prior to these stereotaxic surgical manipulations. Subjects were
      matched for quantitative behavioral deficits prior to surgery. Subjects were
      examined and assessments made by "blinded" observers who scored individual
      spontaneous and elicited behaviors. Observers were trained and tested repeatedly
      for inter-rater reliability. A "parkinsonian summary score" derived and
      determined using a principal component factor analysis of a large sample of data
      from MPTP-treated and normal monkeys of the same species was used to assess
      behavior. Postmortem brain tissue was prepared for biochemical analysis of
      dopamine concentrations and TH immunohistochemical studies. The most dramatic
      improvement was seen in monkeys with "early" (< 4 cm fetal crown rump length)
      surviving substantia nigra grafts in the caudate nucleus. Some behavioral
      improvements were seen in MPTP-treated sham-operated monkeys, cerebellar-grafted
      monkeys, and "later" (> 14 cm fetal crown rump length) substantia nigra-grafted
      monkeys. These changes in monkeys which did not have surviving dopamine-producing
      grafts probably represent the recovery capacity of MPTP-treated host brain during
      this time interval since un-operated subjects showed similar changes. More
      variable effects were seen with substantia nigra grafts in the putamen. The most
      consistent correlate of behavioral improvement in all experimental groups was
      elevation in dopamine concentrations near the grafts compared with a distant
      striatal location which is believed to represent the depletion without the
      effects of the grafts. While these data do not establish the precise mechanism of
      action, they point to a hierarchy of factors which provide increasingly larger
      restorative effects, including sprouting of host neurons and increased dopamine
      production by grafted fetal dopamine neurons. Sham surgery appears to be
      significantly less effective than early fetal mesencephalic tissue which survives
      and releases dopamine.

PMID- 7728328
TI  - Neither intraocular grafts of retinal cell homogenates nor live non-retinal
      neurons produce behavioral recovery in rats with light-damaged retinas.
AB  - Previously we have observed that fetal retinal cells grafted to the subretinal
      space of blind rats produced a functional recovery as determined by testing the
      visual inhibition of the startle response. Following those studies, we performed
      experiments to test whether the injection itself, cell by-products, or unrelated
      neural cells could also produce an effect. Visual function was tested by
      examining the inhibitory effect of a brief light flash (300 lx) on the acoustic
      startle response to an immediately following intense noise burst in light blinded
      Fischer 344 rats. Animals were tested before and after grafts of fetal retinal
      cell homogenates, dissociated perinatal cerebellar cells, and sham injections in
      the subretinal space. Behavioral testing continued every 2 wk for 14 wk after the
      graft. In the pretests, the light flash inhibited the startle response, maximal
      at intervals of 40-70 ms with recovery thereafter. In contrast, after exposure
      for 4 wk to fluorescent light (300 lx) and a rest in a normal 12/12 h light/dark
      environment the rats showed reflex facilitation to the light, maximal at an
      interval of 110 ms, followed by a late period of reflex inhibition. The light
      flash had no effect on other rats that had been blinded by bilateral enucleation.
      Light blinded animals receiving either cerebellar grafts or retinal cell
      homogenates were no different in performance from their sham injected control
      animals. The present data suggest that neither subretinal injections of neural
      cells nor non-specific neurochemical factors are able to elicit a positive
      behavioral response in visually impaired animals.

PMID- 7728329
TI  - The influence of donor age on the survival of solid and suspension
      intraparenchymal human embryonic nigral grafts.
AB  - In many species, graft survival and graft-derived behavioral recovery are
      affected by the embryonic donor age. We compared the ability of solid and
      suspension grafts of human embryonic mesencephalic dopaminergic (DA) neurons at
      different embryonic stages to survive intraparenchymal transplantation into 6
      OHDA lesioned immunosuppressed rats. Suspension grafts survived best when donor
      age was between postconception (PC) days 34 and 56. Transplants displayed
      numerous healthy tyrosine hydroxylase immunoreactive (TH-IR) neurons which sent
      extensive neuritic processes into the host striatum. Suspension grafts survived
      poorly when donor age was greater than 65 days. Solid implants displayed
      comparable viability of TH-IR neurons when donor age was between 44 and 65 days.
      No solid grafts contained TH-IR cells when donor tissue was older than 72 days.
      The suspension and solid methods of transplantation resulted in comparable
      survival of robust grafts, but solid grafts resulted in more intergraft
      variability than suspension grafts, particularly among the more marginal
      implants. Our results demonstrate that the upper limit for survival of human
      embryonic DA suspension grafts correlates well with the period of development of
      the human nigrostriatal pathway. The "window" for donor age of solid human
      embryonic DA grafts appears to be extended by about 9 days in comparison to
      suspension grafts. These data suggest that the upper age limit for grafting human
      mesencephalic DA neurons should be PC day 56 for suspension grafts, and PC day 65
      for solid implants. Older donors are likely to produce grafts with fewer
      surviving DA neurons.

PMID- 7728330
TI  - Intrastriatal cografts of autologous adrenal medulla and sural nerve in MPTP
      induced parkinsonian macaques: behavioral and anatomical assessment.
AB  - To examine the effects of autologous sural nerve and adrenal medullary tissue
      intrastriatal cografts upon voluntary motor performance in parkinsonism, a non
      human primate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model was
      employed to quantitatively assess skilled hand movements. Motor performance was
      studied in normal, MPTP-induced parkinsonian, and then cografted states. Reaction
      and movement times were prolonged and variability increased in experimental and
      control animals in the parkinsonian state. Animals undergoing autologous cografts
      demonstrated improved motor performance whereas the control animal continued in a
      chronic, stable parkinsonian state. Intrastriatal cografts of autologous adrenal
      medullary tissue and sural nerve resulted in good to excellent chromaffin cell
      survival. The mechanism of the restoration of function in the cografted monkeys
      remains to be determined.

PMID- 7728331
TI  - Synapsin I in intraocular hippocampal transplants during maturation and aging:
      effects of brainstem cografts.
AB  - The role of target innervation for maintenance of synaptic proteins in the
      hippocampal formation during aging was investigated. Fetal CA1 tissue and
      brainstem tissue containing the nucleus locus coeruleus was dissected from albino
      rats and grafted sequentially into the anterior chamber of the eye of adult rat
      recipients. Synapsin protein distribution and levels were evaluated by
      immunohistochemistry and quantitative immunolabeling in single hippocampal grafts
      or brainstem-hippocampal double grafts at 6, 12, or 24 mo postgrafting. The
      synapsin levels in 6-mo-old single hippocampal transplants were significantly
      lower than those in situ, and remained at these lower levels at 12 and 24 mo. On
      the contrary, synapsin levels were close to normal in the hippocampal portion of
      double grafts in the 6- and the 12-mo-group. However, in the 24-mo-old double
      transplants the levels had declined significantly, approaching levels seen in
      single hippocampal grafts. The immunoblot results were supported by morphological
      observations with synapsin antibodies and immunohistochemistry. The present data
      demonstrate that hippocampal tissue maintained near normal synapsin levels when
      grafted together with brainstem tissue, as compared to the lower levels seen in
      single hippocampal grafts. This normalization of synapsin levels was, however,
      not seen in the aged hippocampal-brainstem double grafts.

PMID- 7728332
TI  - Ventral mesencephalic grafts in the neostriatum of the weaver mutant mouse:
      structural molecule and receptor studies.
AB  - Mesencephalic cell suspensions were prepared from E12 wild-type (+/+) mouse
      embryos and stereotaxically implanted into the dorsal neostriatum of weaver
      mutant mice (wv/wv), which have a genetic mesostriatal dopamine (DA) deficiency.
      Survival of DA neurons in the grafts was documented by tyrosine hydroxylase (TH)
      immunocytochemistry. Axon growth was monitored by immunocytochemistry using a
      battery of antibody markers, and the cellular localization of structural protein
      and receptor RNA transcripts was studied by in situ hybridization histochemistry
      using [32P]oligonucleotide probes. The cell suspension grafts exhibited strong
      immunoreactivity for neural cell adhesion molecule (N-CAM), growth-associated
      phosphoprotein GAP-43, microtubule-associated protein 2 (MAP2), beta-amyloid
      protein precursor (beta APP), and phosphorylated neurofilament epitopes (clone
      SMI-31); intermediate-to-high levels of immunoreactivity were seen for
      synaptophysin. High levels of hybridization were found in the grafts for the RNA
      transcripts of GAP-43, MAP2, and isoforms beta APP695, beta APP714 and beta
      APP751 of the beta APP. No hybridization signal was detected in the grafts for DA
      D2 or neurotensin receptor mRNAs, both of which are normally expressed by nigral
      DA neurons. DA receptor autoradiography using the D2/D3 agonist [3H]CV 205-502 as
      a ligand showed no binding in the transplants, indicating an apparent abnormality
      of grafted cells; neurotensin binding sites, labeled with [125I]neurotensin, were
      visualized in the suspensions, indicating the possibility that receptors could be
      present but that RNA message levels might be too low to allow detection. These
      findings offer a molecular correlate of axonal, dendritic and structural protein
      expression by transplanted mesencephalic neurons; further, they suggest that
      specific functional properties of grafted nigral cells are maintained after
      transplantation, while other aspects of their cellular biology may be
      compromised.

PMID- 7728333
TI  - Neural transplantation of cells expressing the anti-apoptotic gene bcl-2.
AB  - Long-term survival of grafted neural cells is a major goal of neural
      transplantation, but typical survival rates of grafted fetal neurons are in the
      range of 5-10%. Whether the death of transplanted neural cells is apoptotic or
      necrotic is unknown. The expression of the proto-oncogene bcl-2 inhibits both
      apoptotic and necrotic neural cell death. In a 6-OHDA induced rat model of
      Parkinson's disease, Hoechst 33258 prelabelled conditionally immortalized nigral
      cells engineered to express bcl-2 were stereotactically transplanted into the
      striatum ipsilaterally to the lesioned nigrostriatal pathway. Sixteen rats
      received bcl-2 transfected cells, 15 received cells transfected with vector
      alone, and 12 received either a nondopaminergic cell line or were sham
      transplanted as controls. Four wk following transplantation, the rats with grafts
      containing bcl-2 expressing cells showed an approximately 43% decrease in
      apomorphine-induced rotational behavior. In contrast, 12% improvement occurred in
      the rats with transplanted cells transfected with vector alone (p < 0.05), and no
      improvement occurred in sham-operated animals (p < 0.05). Histological
      examination showed no tumor formation. Despite the difference in behavioral
      effect, no clear difference in Hoechst fluorescent staining or staining for TH,
      GFAP was noted; therefore, it is unknown at present whether the observed effect
      was due to a difference in survival or to increased efficacy per surviving
      transplanted neural cell, or both.

PMID- 7728334
TI  - Long-term viability of isolated bovine adrenal medullary chromaffin cells
      following intrastriatal transplantation.
AB  - Adrenal medullary grafts generally exhibit poor viability when grafted into the
      striatum. Previous work in our laboratory demonstrated that chromaffin cells can
      survive well for up to 2 mo following grafting into the intact rat striatum after
      cells are isolated from the nonchromaffin supporting cells (fibroblasts and
      endothelial cells) of the adrenal medulla. The aim of the present study was to
      assess the long-term viability of isolated bovine chromaffin cells following
      grafting into the intact rat striatum. The viability of grafted bovine adrenal
      medullary chromaffin cells was compared in rats receiving either (a) perfused
      adrenal medulla; (b) isolated chromaffin cells; or (c) isolated chromaffin cells
      that were subsequently recombined with their nonchromaffin supporting cells. One
      year postimplantation, all graft types which included fibroblasts and endothelial
      cells were infiltrated with macrophages and demonstrated an abundance of cellular
      debris. No viable chromaffin cells were observed. In contrast, healthy tyrosine
      hydroxylase (TH) and dopamine beta hydroxylase (D beta H) immunoreactive
      chromaffin cells survived for 1 yr posttransplantation when grafted in isolation
      from the nonchromaffin constituents of the adrenal medulla. Good xenograft
      survival was achieved in this group despite the fact that these rats were only
      immunosuppressed for 1 mo postimplantation. Grafted cells demonstrated
      morphological characteristics of chromaffin cells in situ and these implants were
      not accompanied by macrophage infiltration. These data demonstrate that long-term
      survival of chromaffin cells can be achieved following intrastriatal implantation
      and the viability of grafted chromaffin cells is dependent upon the removal of
      the nonchromaffin supporting cells.

PMID- 7728335
TI  - Cyclosporine-A increases spontaneous and dopamine agonist-induced locomotor
      behavior in normal rats.
AB  - Cyclosporine-A (CsA) has been increasingly used as an immunosuppressant
      concomitant with neural transplantation treatment for different degenerative
      disorders. However, the possible role that CsA itself may have in the recovery of
      transplant patients is not known. Some investigators have argued that clinical
      improvement following transplantation (e.g., myoblast) may be confounded by CsA
      administration. The present study was conducted to delineate CsA-induced
      behavioral alterations. Four groups of normal 5-wk old Sprague-Dawley rats (n = 8
      per group) were utilized in two separate experiments. In both experiments, two
      groups of animals were used; each group either received daily injections of 15
      mg/kg of CsA or olive oil for 32 days (experiment 1) and 21 days (experiment 2).
      Animals in both experiments were subsequently tested for nocturnal locomotor
      behavior. Animals in experiment 2 were further tested in passive avoidance task,
      motor coordination, and amphetamine-induced locomotor activity. Results
      demonstrated that CsA-treated animals were significantly hyperactive compared to
      controls across the 12-h nocturnal activity periods and in amphetamine-induced
      locomotor activity. No significant differences between the CsA- and vehicle
      treated animals were observed in passive avoidance or in motor coordination.
      Postmortem analyses of dopamine and its metabolites in the striatum and olfactory
      tubercle did not show any significant differences between the CsA- and the
      vehicle-treated groups. In summary, CsA significantly increased nocturnal
      spontaneous and amphetamine-induced locomotor behavior, but the neurochemical
      correlates for these effects need to be investigated. In addition, while the
      present study demonstrated that CsA induced motor alterations, any possible
      effects CsA may have on neurological or dystrophic patients with motor
      dysfunctions remain to be determined.

PMID- 7728336
TI  - How do fetal grafts of the suprachiasmatic nucleus communicate with the host
      brain?
AB  - Fetal grafts containing the hypothalamic suprachiasmatic nucleus (SCN), the site
      of an endogenous circadian pacemaker, can reinstate behavioral rhythms in
      lesioned recipients but the precise routes of communication between the graft and
      the host brain remain unknown. Grafts containing the SCN may convey temporal
      information to the host brain via neural efferents, diffusible factors, or a
      combination of both. We examined graft-host connections in anterior hypothalamic
      homografts (hamster-to hamster) and heterografts (rat-to hamster) implanted in
      the third ventricle by: (a) applying the carbocyanine dye, diI, directly onto
      homo- and heterografts in fixed tissue sections; and (b) using a donor-specific
      neurofilament (NF) antibody to immunocytochemically visualize heterograft
      efferents. DiI applied onto either homografts or heterografts labeled relatively
      few graft efferents which could be followed only short distances into the host
      brain. In contrast, NF-labeled heterograft efferents were both more numerous and
      extended for longer distances into the host brain than anticipated on the basis
      of diI tract tracing. The results suggest that anterior hypothalamic grafts
      implanted in the third ventricle provide substantial input to the adjacent host
      hypothalamus although it is not known whether these projections arise from SCN
      cells or from other extra-SCN hypothalamic tissue within these grafts. Nor is it
      known whether these projections are functional. To determine if neural efferents
      are required for the restoration of rhythmicity after grafting, we have
      encapsulated fetal anterior hypothalamus in a permselective polymer which
      prevents neurite outgrowth but allows diffusible signals to reach the host
      brain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728337
TI  - Diminished expression of microtubule-associated protein (MAP-2) and beta-tubulin
      as a putative marker for ischemic injury in neocortical transplants.
AB  - The present study examined the immunoexpression of the neuronal cytoskeletal
      proteins, MAP-2 and beta-tubulin within a timed series of rat fetal neocortical
      transplants. beta-tubulin is a major component of microtubules and MAP-2
      regulates the assembly and stability of neuronal microtubules and is a major site
      for the phosphorylation cAMP dependent protein kinase in neurons. Both proteins
      are strongly expressed in the soma and dendrites of normal neurons. MAP-2 has
      been shown to be a sensitive marker for ischemia in neurons and is downregulated
      in this form of injury. Immunoexpression of both MAP-2 and beta-tubulin in
      grafted cortical neurons was markedly reduced when compared to age-matched or
      even perinatal specimens at all post-operative times. Dendritic staining was
      confined to random, thin processes with no laminar patterns and staining within
      somata was very weak. In some specimens, somatic expression was increased and
      dendrites were more robustly stained when a portion of the graft was juxtaposed
      to a fiber tract even though in other regions of the same graft there was very
      weak immunostaining. The present results corroborate previous studies of cortical
      transplants indicating an immature structure and metabolism, and it is suggested
      here that the primary factor is a sublethal form of ischemic injury. Another
      possibility for the relative paucity of cytoskeletal protein expression could be
      that transplanted neurons undergo a new developmental scheme (neodevelopment)
      that is brought about by truncated migration patterns and abnormal synaptic
      connections.

PMID- 7728338
TI  - Polymer-encapsulated Schwannoma cells expressing human nerve growth factor
      promote the survival of cholinergic neurons after a fimbria-fornix transection.
AB  - Many investigators have recently used genetically modified primary fibroblasts of
      fibroblast cell lines (e.g., 3T3, 208F, or BHK cells) to deliver recombinant
      nerve growth factor (NGF) into the CNS. In the current study, SCT-1 cells, a
      Schwannoma cell line derived from a transgenic mouse, were transfected with a
      human NGF (hNGF) cDNA. After selection, these cells were encased within a polymer
      capsule and implanted into the ventricles of fimbria-fornix lesioned rats.
      Encapsulated, non-transfected cells served as controls. Results demonstrated that
      the hNGF transgene is expressed for at least 3 weeks after implantation.
      Moreover, the cells did not overgrow the capsule. Recombinant hNGF was able to
      save > 70% of lesioned cholinergic neurons, as assessed by NGF-receptor (NGFr)
      and choline acetyltransferase (ChAT) immunohistochemistry, from cell death. The
      number of cholinergic neurons in animals that received control capsules (i.e.,
      nontransfected SCT-1 cells) was similar to lesion only animals (i.e.,
      approximately 27% and approximately 33% for NGFr- and ChAT-positive neurons,
      respectively. These results show that SCT-1 cells can be used to deliver
      biologically active hNGF into the lesioned rat brain.

PMID- 7728339
TI  - Pancreatic development and anatomical variation.
AB  - The pancreas is formed by the fusion of the ventral and dorsal anlage, and a wide
      spectrum of anomalies or anatomical variations may appear related to this
      complicated process of fusion: e.g., agenesis, aplasia of a pancreatic anlage,
      hypoplasia, annular pancreas, pancreas divisum or nonfusion of the ventral and
      dorsal duct system, pancreaticobiliary maljunction, etc. Every endoscopist who
      engages in pancreatography or related diagnostic and therapeutic procedures
      should always be aware of all sorts of anatomical variations he or she might
      encounter.

PMID- 7728340
TI  - What does an abnormal pancreatogram mean?
AB  - The foregoing discussion emphasized the fact that pancreatography can document
      changes that are relatively specific for chronic pancreatitis but that similar
      changes can be seen in other clinical conditions and even as normal variants. In
      addition, the exact clinical implication of minor or equivocal changes is unclear
      and care should be taken not to overinterpret ERP findings. It also must be
      realized that ERP may miss a substantial number of patients with earlier or less
      advanced chronic pancreatitis. ERP also may document pancreas divisum, but is not
      helpful in explaining the patient's clinical condition in the absence of dorsal
      duct abnormalities. Finally, tests of pancreatic function--in particular,
      hormonal stimulation tests--are complementary to tests of pancreatic morphology
      and allow the diagnosis of less advanced or earlier chronic pancreatitis, as well
      as patients with divisum and normal dorsal ducts who nonetheless have obstruction
      to flow at the minor papilla. The evaluation of a patient with presumed chronic
      pancreatitis therefore should begin with simple, noninvasive tests that are able
      to detect advanced forms of chronic pancreatitis. These include plain abdominal
      radiograph and serum trypsin. If either of these is markedly abnormal, no further
      diagnostic testing is generally required. In patients in whom diagnostic
      uncertainty still exists, reasonable second-echelon tests include abdominal CT,
      bentiromide testing, or secretin stimulation testing. Of these, hormonal
      stimulation testing offers the most sensitivity but is not universally available.
      More invasive evaluations--in particular, ERP--should be reserved for patients in
      whom the diagnosis is still unclear or in whom therapeutic rather than diagnostic
      information is required (e.g., a patient classified a medical failure being
      considered for Peustow procedure).

PMID- 7728341
TI  - Assessment of pancreatic duct strictures.
AB  - It should be fairly clear that the evaluation of pancreatic duct strictures is
      complex. Short of surgical resection, there is no gold standard that will provide
      an etiological diagnosis unless cancer is found on a biopsy specimen. To
      complicate matters further, much of the literature was generated in reference to
      differentiating between pancreatic cancer and pancreatitis. Using the same data
      to evaluate the patient with a pancreatic duct stricture may not be appropriate
      because the clinical scenario may not be comparable. Bearing these shortcomings
      in mind, however, a thoughtful history combined with the judicious use of
      abdominal imaging, ERCP, and the biopsy techniques discussed will lead to a
      clinical diagnosis that usually will prove to be correct in most cases. The role
      of tumor markers in patients with pancreatic duct strictures is still being
      defined. Although no tumor marker has proved especially helpful so far, the
      potential exists that a more useful one is just over the horizon. In situations
      in which the diagnosis remains uncertain, exploratory laparotomy in an
      appropriate surgical candidate by an experienced pancreatic surgeon will provide
      a definitive diagnosis in almost all cases.

PMID- 7728342
TI  - Pancreas divisum. Diagnosis, clinical significance, and management alternatives.
AB  - Pancreas divisum patients make up a small but problematic portion of ERCP cases.
      Minor papilla cannulation techniques have been refined. Recurrent pancreatitis
      patients generally will benefit from minor papilla therapy. Methods to select
      patients who are likely to respond to invasive therapy and further study need
      validation. Clinicians and endoscopists are strongly encouraged to be cautious
      and conservative with this patient group until stronger data indicate optimal
      management schemes.

PMID- 7728343
TI  - Endoscopic therapy for pancreatic pseudocysts.
AB  - The management of pancreatic pseudocysts is complex. It demands an understanding
      of the natural history of the disease and an appreciation of the strengths and
      weaknesses of the treatment options available. Endoscopic therapy represents a
      valuable alternative to surgery in the subset of patients with appropriate
      anatomy. Success and relapse rates for endoscopic treatment of pancreatic
      pseudocysts are comparable to alternative methods, but require careful patient
      selection and operator expertise. Complication rates vary widely in published
      studies. It is hoped that technical innovation will reduce the risks. For
      example, the use of an aspiration needle to localize the pseudocyst and
      endoscopic ultrasound to define local vascular anatomy are significant advances.
      Strictly limiting the size of the opening created in cyst-gastrostomy and cyst
      duodenostomy should reduce the risk of hemorrhage. Although technically
      difficult, transpapillary drainage is an option worth considering in patients
      with fluid collections associated with pancreatic ductal disruption. No single
      technique offers the desired combination of 100% success and no complications.
      Surgery, percutaneous drainage, and therapeutic endoscopy offer a variety of
      treatment options that can be tailored to the needs of individual patients with
      pancreatic pseudocyst.

PMID- 7728344
TI  - Endoscopic therapy of pancreatic stones.
AB  - This chapter provides an overview of the physiology of pancreatic exocrine
      function and the pathophysiology of pancreatic stone formation. The natural
      history and the clinical sequelae are reviewed. Potential pharmacologic
      intervention is addressed and a detailed description and analysis of the
      endoscopic management is outlined.

PMID- 7728345
TI  - Pancreatic and ampullary carcinoma.
AB  - Surgery should be the first therapeutic modality considered in patients with
      pancreatic and ampullary carcinoma. Surgery is the only potentially curative
      therapy and offers the best form of palliation in patients with impending or
      overt duodenal obstruction. Patients with clearly unresectable tumors or those
      considered unfit for surgery should be offered palliative therapy, preferably
      endoscopically. The difficulty, however, arises in patients who undergo
      laparotomy and who subsequently are found to have unresectable tumors. The
      problem of stent occlusion and frequent associated hospital visits has been an
      argument to proceed to palliative double bypass surgery. Against this is the low
      mortality and shorter hospital stay of nonsurgical endoscopic palliative therapy.
      Direct comparisons of surgery versus endoscopic therapy have shown that both are
      equally effective in the initial relief of jaundice (Table 6). Surgery has a
      higher initial mortality and complication rate, but more long-term complications
      and hospital visits were seen in the endoscopic group, suggesting that it offered
      a poorer long-term palliation. There was no significant difference in the
      survival of the patients in the two groups. Patient choice is a major factor in
      the final decision, but current recommendations probably should be that patients
      with a poor short-term survival outlook should be offered nonsurgical palliative
      therapy and those with a longer life expectancy may best be handled with surgery.
      Predicting patient survival, of course, remains a major difficulty. A recent
      publication of the laparoscopic formation of a cholecystojejunostomy for
      palliation of malignant biliary obstruction also offers a promising approach that
      requires further evaluation.

PMID- 7728346
TI  - Mucin-secreting tumors of the pancreas.
AB  - Mucinous pancreatic neoplasms present diagnostic and therapeutic challenges.
      These tumors behave in an indolent nature, with frequent overlap of symptoms and
      radiographic appearance with other forms of pancreatic cysts, pseudocysts, and
      malignancy. Some authors propose that all mucin-producing tumors of the pancreas
      are variants of the same basic entity and have subclassified them on the basis of
      their predominant location within the pancreas. These disorders must be
      considered in the evaluation of chronic abdominal pain, particularly in the
      presence of a cystic pancreatic lesion or when associated with idiopathic chronic
      or acute recurrent pancreatitis. The clinicopathologic features of IMHN overlap
      to a great extent with classic mucinous cystic neoplasms but are different
      significantly enough to be distinct clinical entities. These tumors originate
      from the pancreatic duct epithelium, produce mucin, demonstrate a papillary
      growth pattern, and are considered premalignant or frankly malignant at the time
      of diagnosis. Both lesions biologically are much less aggressive than that of
      pancreatic ductal adenocarcinoma and appear to infiltrate peripancreatic tissue
      and to metastasize to lymph nodes or other adjacent structures late in the course
      of disease. Nevertheless, IMHNs are located primarily in the head of the
      pancreas, commonly affect elderly men, and present clinically with obstructive
      pancreatitis, often leading to pancreatic insufficiency, whereas mucinous cystic
      neoplasms are more likely to develop in the pancreatic body or tail, predominate
      in young women, and present with symptoms referable to tumor compression of
      adjacent structures. The location of the lesion is the primary differentiating
      feature because the lining epithelium of the two tumor types is indistinguishable
      pathologically. In mucinous cystic tumors, the mucus is secreted and retained
      within the cyst lumen because of the absence of communication between the cyst
      and the main pancreatic duct. In contrast, mucus produced in MDE flows into the
      main pancreatic duct, resulting in obstructive pancreatitis and, ultimately,
      dilatation of the pancreatic duct. Intraductal mucus provides an important clue
      to the diagnosis of intraductal pancreatic neoplasms and, whenever present,
      should prompt an aggressive diagnostic evaluation. Both lesions are managed by
      resectional surgery because the opportunity for cure is high in the absence of
      metastatic disease.

PMID- 7728347
TI  - Direct pancreatoscopy.
AB  - Direct pancreatoscopy has inherent limitations, which include lack of instrument
      availability, scope fragility, small image size, lack of traditional endoscope
      features, and need for two endoscopists. Despite the above, centers with large
      pancreaticobiliary referral practice will selectively use this technology both
      diagnostically and therapeutically. The variability of pancreatic duct angulation
      and diameter, the presence of variably obstructing stenoses or filling defects,
      and the need to concomitantly apply this technology to the biliary tree all
      suggest that a family of miniscopes will be required as opposed to a single
      "ideal" instrument.

PMID- 7728348
TI  - Pancreatography and the surgical management of pseudocysts.
AB  - Endoscopic pancreatography has played a dominant role in the evolution of
      surgical treatment of pancreatic pseudocysts. This article presents an algorithm
      for the management of pseudocyst disease, focusing on pancreatography and
      elective treatment. Pancreatography's roles in refining operative strategies,
      identifying associated pancreatic and biliary disease, and predicting outcome of
      nonoperative treatment are reviewed.

PMID- 7728349
TI  - Computed tomography and magnetic resonance imaging in the assessment of
      pancreatic disease.
AB  - Significant technical advances have occurred in both computed tomography (CT) and
      magnetic resonance (MR) imaging that have resulted in improved visualization of
      the pancreas by both techniques. In this article we will consider the advances in
      both modalities and consider the relative roles of each in imaging the spectrum
      of pancreatic pathology.

PMID- 7728350
TI  - Endoscopic ultrasonography of the pancreas.
AB  - The pancreas is the most technically demanding area to image with EUS. This
      technique, however, has found a clinical niche in evaluating patients with
      pancreatic cancer to determine resectability and likely will play a prominent
      role in the future in diagnosis through ultrasonographically directed FNA. Its
      role in localization of neuroendocrine tumors is established as long as
      preoperative localization is important in management. It is unlikely that a
      competing technology will develop in the near future with resolution the same or
      better than EUS. The role of EUS in the evaluation of early chronic pancreatitis
      is still under investigation, but it is likely that it can play a role adjunctive
      to ERCP. If FNA can be demonstrated to be safe and the interpretation of the
      cytology is accurate, then EUS could play an important role in this area. In the
      future, EUS may be used to acutely aspirate pancreatic pseudocysts and
      potentially could be useful in differentiating pseudocysts amenable to endoscopic
      drainage versus those that would be managed best by percutaneous or surgical
      drainage. With some design modifications, it may be feasible in the future to use
      ultrasonographic guidance to puncture pseudocysts and then place nasocystic
      drains or internal stents. These areas will need further investigation and
      further technological development.

PMID- 7728351
TI  - Retrograde pancreatography. Technical tips and spectrum of pathology.
AB  - ERP is an important technique in the diagnosis of diseases involving the
      pancreatic ducts, in determining therapeutic strategy, and in assessing the
      results of surgical bypass procedures. ERP facilitates the diagnosis of the
      majority of pancreatic tumors at a stage when they normally present to the
      clinician. It assists the diagnosis of small tumors in the ampullary region at an
      early stage when other tests are negative. In cases of obscure recurrent
      pancreatitis, ERP may identify a mechanical cause (e.g., stone, stricture). ERP
      is useful in the diagnosis of CCP only in the precalcified stage. If histologic
      confirmation already has been obtained at surgery, ERCP is not required. Compared
      with noninvasive techniques, ERP provides additional information: It enables a
      concomitant examination of the gastroduodenal tract and opacification of the bile
      ducts; additional procedures may be performed, such as intraductal cytologic
      brushings, biochemical and cytologic analysis of pancreatic juice, endoscopic
      manometry, and pancreatoscopy. The diagnostic yield is increased if these
      procedures are performed during ERCP. Because ERP outlines the ductal anatomy, it
      is of great value in assessing therapeutic strategy. In cases of acute recurrent
      pancreatitis or chronic pancreatitis, ERP provides an important baseline for
      performing procedures such as ductal drainage and therefore reduces the
      inappropriate use of exploratory laparotomy. In cases of necrotic pancreatitis or
      pancreatic trauma, ERP enables accurate localization of a pancreatic fistula and
      facilitates any subsequent surgical procedure. Finally, ERP is the method of
      choice when assessing the patency of pancreatic-digestive anastomosis.

PMID- 7728352
TI  - Processing of bacterial antigens for presentation to class I and II MHC
      restricted T lymphocytes.
AB  - Phagocytosis leads to the destruction of many bacteria and the proteolytic
      degradation of bacterial antigens within phagolysosomes to produce immunogenic
      peptides that bind to Class II major histocompatibility (MHC) molecules within
      vacuolar compartments. On the other hand, Class I MHC molecules bind cytosol
      derived peptides, including peptides from bacteria that escape the vacuolar
      system and penetrate into the cytosol. A recently described pathway may also
      allow the presentation of peptides from intravacuolar organisms by Class I MHC
      molecules in some cases. T cell recognition of peptide-MHC complexes then
      provides the primary basis for specific immunity to protein antigens of bacteria.
      This article will review the subcellular compartments and mechanisms involved in
      generating immunogenic peptides, the subcellular localization of MHC molecules
      that bind these peptides, and bacterial parameters that affect antigen
      processing.

PMID- 7728353
TI  - Development of a meningococcal vaccine.

PMID- 7728354
TI  - Hypoxanthine-guanine phosphoribosyltransferase as a therapeutic target in
      protozoal infections.
AB  - The auxotrophy of parasitic protozoa for purines makes purine acquisition from
      the host a nutritional necessity for the survival and growth of these pathogens.
      The parasite hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme has
      been implicated as a critical enzyme in this purine salvage process. Moreover,
      the HGPRT enzyme in some parasites can also initiate the metabolism of purine
      base analogs that have little effect on the mammalian host. This implies that
      either inhibitors or substrates of HGPRT might serve as efficacious and selective
      agents for the treatment of parasitic diseases. This commentary provides an
      overview of recent molecular and biochemical studies on HGPRT proteins from
      parasitic protozoa and a discussion of the potential of HGPRT as a rational
      target for the chemotherapeutic manipulation of parasitic diseases.

PMID- 7728355
TI  - Vibrio cholerae O139 Bengal: emergence of a new epidemic strain of cholera.
AB  - In October 1992, a new strain of cholera, subsequently designated Vibrio cholerae
      O139 Bengal, was detected in Madras, India. This strain spread rapidly through
      the Indian subcontinent and has now been reported in many parts of Asia, with
      additional cases identified in travelers to North American and the Middle East.
      Phylogenetically, V. cholerae O139 Bengal is very closely related to "standard"
      V. cholerae O1 El Tor strains; it produces cholera toxin and causes an illness
      identical that seen with V. cholerae O1. However, prior immunity to V. cholerae
      O1 El Tor does not appear to protect against illness caused by V. cholerae O139
      Bengal. O139 Bengal strains have a short, "semi-rough" O side chain and are
      encapsulated, changes that are likely to have accounted for their ability to
      cause disease in persons with prior exposure to cholera. These changes in surface
      structures appear to have resulted from a limited number of genetic
      modifications. The appearance of V. cholerae O139 Bengal may well herald the
      beginning of the eighth pandemic of cholera--and underscores the tremendous
      potential within nature for creation of new strains of "old" pathogens.

PMID- 7728357
TI  - International policies on addiction. Strategy development and cooperation.

PMID- 7728356
TI  - Proteases and bacterial virulence: a view from the trenches.
AB  - Many species of pathogenic bacteria produce cell-surface or secreted proteases.
      These enzymes have high potential to enhance bacterial pathogenesis through
      degradation of critical host proteins and by mimicking the activity of host
      regulatory proteases that control important zymogen systems. Although many
      bacterial proteases have been implicated in virulence, there is currently no
      system in which both rigorous demonstration of virulence enhancement in vivo and
      convincing identification of the important substrate molecules has been achieved.
      The difficulties inherent in addressing these issues is discussed, and several
      interesting systems under active investigation briefly described. The potential
      of extracellular protease as targets for drug development is also considered.

PMID- 7728358
TI  - The addicted doctor. Caring professionals?

PMID- 7728359
TI  - The Korsakoff syndrome.
AB  - BACKGROUND: Investigations of the Korsakoff syndrome by researchers from
      different disciplines have proliferated in recent years, making it apposite to
      review the various findings. METHOD: This review is based on the author's
      knowledge of reports in the major clinical and neuropsychological journals,
      supplemented by Medline searches to update particular subtopics. RESULTS: The
      Korsakoff syndrome is defined as a disproportionate impairment in memory,
      relative to other aspects of cognitive function, resulting from a nutritional
      (thiamine) depletion. The initial manifestations of the disorder are variable,
      and a persistent memory impairment can result from a non-alcoholic aetiology,
      although this seems to happen much less commonly than in the past - presumably
      because of generally higher standards of nutrition. Although there is agreement
      on the underlying neuropathology, the critical lesion sites for memory disorder
      have been debated. Recent evidence suggests that the circuit involving the
      mammillary bodies, the mammillo-thalamic tract and the anterior thalamus, rather
      than the medial dorsal nucleus of the thalamus, is particularly critical in the
      formation of new memories. The relationship of these deficits to thiamine
      depletion remains a topic of current investigation, as does the purported role of
      neurotransmitter depletions in the cholinergic, glutamate/GABA and catecholamine
      and serotonergic systems. Neuro-imaging studies have confirmed autopsy findings
      of more widespread structural and metabolic abnormalities, particularly involving
      the frontal lobes. CONCLUSIONS: The relationship of these neuropathological,
      neurochemical, and metabolic abnormalities to cognitive functioning, with
      particular reference to specific aspects of memory processing, has been
      considered in some detail. Whereas structural and/or neurochemical abnormalities
      within the limbic/diencephalic circuits account for anterograde amnesia, some
      other factor, such as frontal lobe dysfunction, must underlie the severe
      retrograde memory loss which is characteristically found in this syndrome.

PMID- 7728360
TI  - Dysthymia in clinical practice. The WPA Dysthymia Working Group.
AB  - BACKGROUND: Dysthymia has been reconceptualised in recent years from a
      personality disorder to a chronic affective disorder. It is incorporated into
      both the DSM and ICD diagnostic systems. METHOD: The members of the WPA Dysthymia
      Working Group combined the results of their manual literature searches with a
      search using Medline. RESULTS: Available data are summarised under the headings
      of classification, epidemiology, validity, comorbidity, course and outcome,
      pharmacotherapy and psychotherapy. The coexistence of major depressive disorder,
      constituting 'double depression' is of particular importance. CONCLUSIONS:
      Improved knowledge of this disorder has led to a more positive approach to
      treatment, in which antidepressants can usefully be complemented by psychosocial
      measures. A high proportion of cases remain unrecognised in most populations,
      leading to prolonged morbidity and distress, much of which is now treatable.

PMID- 7728361
TI  - Decision analysis in psychiatry.
AB  - BACKGROUND: Decision analysis is an explicit, quantitative approach to examining
      difficult decisions about course of action. Its applicability to psychiatry is
      considered. METHOD: An example of how decision analysis could be used in
      psychiatry is given, criticism of the technique is discussed, and previous
      attempts to apply it to mental illness problems (from a Medline search from 1966
      onwards) are reviewed. CONCLUSION: The future for decision analysis in psychiatry
      lies in teaching, audit and research, rather than clinical work.

PMID- 7728362
TI  - Course and recurrence of postnatal depression. Evidence for the specificity of
      the diagnostic concept.
AB  - BACKGROUND: It is unclear whether the causative factors of non-psychotic
      postnatal depression are the same as those of depression at other times. METHOD:
      The course and recurrence of postnatal depression was studied in two groups of
      primiparous women experiencing an index episode of postnatal depression: those
      for whom the mood disorder had arisen de novo (n = 34), and those for whom it was
      a recurrence of previous affective disturbance (n = 21). The mental state of
      these two groups, together with a psychiatrically well control group (n = 40),
      was studied for five years. RESULTS: It was found that those for whom the index
      episode was a recurrence of depression were at raised risk of further non
      postpartum episodes but not postpartum episodes, and that those for whom the
      index episode had arisen de novo were at raised risk for further episodes of
      postnatal depression but not for non-postpartum episodes. CONCLUSION: These
      findings suggest a specific nosologic reference for the concept of postnatal
      depression.

PMID- 7728363
TI  - Effect of fluoxetine on melatonin in patients with seasonal affective disorder
      and matched controls.
AB  - BACKGROUND: The aim was to investigate the secretion profile of melatonin and
      seasonal affective disorder before and after treatment with fluoxetine. METHOD: A
      six-week case-controlled study with repeated overnight blood sampling was
      conducted. Ten patients fulfilling the criteria for major depressive disorder,
      seasonal type, with a 29-item Hamilton Depression Rating Scale (HDRS) score of at
      least 20 were compared with ten age- and sex-matched healthy controls in a
      clinical laboratory. The effects of fluoxetine (20 mg/day) on the HDRS and
      melatonin concentration were measured. RESULTS: Fluoxetine significantly reduced
      melatonin levels in both groups. There was no significant difference in melatonin
      secretion between the groups. CONCLUSIONS: The effect of fluoxetine differs from
      tricyclics and fluvoxamine, both of which increase melatonin.

PMID- 7728364
TI  - Diagnosis of depression in alcohol dependence: changes in prevalence with
      drinking status.
AB  - BACKGROUND: Depression and alcohol dependence are frequently found to co-exist
      but the relationship between these disorders requires further elucidation. This
      study tested several hypotheses related to the relevance of whether the diagnosis
      of depression was made before admission or after detoxification in the current
      episode for those with alcohol dependence. METHOD: The Schedule for Affective
      Disorders and Schizophrenia (SADS) was administered to obtain Research Diagnostic
      Criteria (RDC) on 82 randomly selected alcohol dependent in-patients. Alcohol
      related (Severity of Alcohol Dependence Questionnaire (SADQ), alcohol consumption
      and alcohol-related problems), socio-demographic variables and treatment for
      depression were assessed. RESULTS: For the episode of drinking which led to
      admission, a diagnosis of major depression was found in the majority of patients
      (67%). Once detoxification from alcohol took place, only the minority (13%) met
      criteria for major depression. CONCLUSIONS: It is suggested that depression is
      largely associated with the episode of drinking which led to admission in
      patients who are dependent on alcohol and may be due to the effect of chronic
      alcohol intoxication. Socio-demographic and alcohol-related characteristics
      appear to bear little relation to the presence of depression. Clinicians exercise
      appropriate judgement in not prescribing antidepressant treatments to patients
      whose depression may remit with abstinence from alcohol.

PMID- 7728365
TI  - Psychotic states arising in late life (late paraphrenia) psychopathology and
      nosology.
AB  - BACKGROUND: This study explored the psychopathological state of a sample of 'late
      paraphrenic' patients and the reliability of their diagnosis according to the
      most widely used systems of classification of mental disorders. METHOD: The
      presence and severity of psychiatric symptoms were assessed with the Present
      State Examination (PSE), the Scale for the Assessment of Positive Symptoms
      (SAPS), and the High Royds Evaluation of Negativity (HEN) scale. Patient signs
      and symptoms were classified according to the PSE9-CATEGO4, DSM-III-R, DSM-IV,
      and ICD-10 diagnostic systems. Agreement among the 11 most widely used criteria
      for the diagnosis of schizophrenia was assessed for these patients. These
      included DSM-III-R, DSM-IV, ICD-10, Schneider, Langfeldt, New Haven Schizophrenia
      Index, Carpenter, Research Diagnostic Criteria (RDC), Feighner, Taylor & Abrams,
      and PSE9-CATEGO4. The study assessed 47 patients, including in-patients, out
      patients, day-patients, and those in the community. Thirty-three elderly controls
      were recruited from luncheon clubs in Southwark and Lambeth (London, UK).
      RESULTS: Patients showed a wide range of delusional ideas, most frequently
      involving persecution (83.0%) and reference (31.9%). Eighty-three per cent of
      patients reported some sort of hallucination, most frequently auditory (78.7%).
      Formal thought disorder was very rare, only one patient showing mild signs of
      circumstantial speech. No patients exhibited catatonic symptoms or inappropriate
      affect. Shallow, withdrawn, or constricted affect was found in only 8.5% of
      patients. The various systems of classification indicated that most patients
      displayed typical schizophrenic symptoms, although up to one-third of them did
      not meet criteria for the diagnosis of schizophrenia. There was poor agreement
      among the different diagnostic schedules as to whether to classify patients as
      schizophrenic (0.02 < k < 0.45). CONCLUSION: Psychotic states arising in late
      life are accompanied by various psychiatric symptoms that are not entirely
      typical of early-onset schizophrenia. The current trend to include 'late
      paraphrenia' into the diagnosis of schizophrenia or delusional disorder has poor
      empirical and theoretical bases.

PMID- 7728366
TI  - Psychotic states arising in late life (late paraphrenia). The role of risk
      factors.
AB  - BACKGROUND: This study explored the association between 'late paraphrenia' and
      various risk factors such as female gender, sensory impairment, marital status,
      positive family history of psychoses, and the presence of abnormal neurological
      signs. It was hypothesised that patients would show significantly more abnormal
      neurological signs than controls. METHOD: Inclusion criteria for the diagnosis of
      late paraphrenia were fulfilled by 47 patients, including in-patients, out
      patients, day-patients, and those living in the community. Thirty-three age-, sex
      , education-, and premorbid IQ-matched elderly controls were recruited from
      luncheon clubs in Southwark and Lambeth (London, UK). A scale for the assessment
      of neurological soft and hard signs was developed for this study. The Abnormal
      Involuntary Movement Scale (AIMS) and the Tardive Dyskinesia Rating Scale (TDRS)
      were also used. RESULTS: There was a high female-to-male ratio (42:5), and a
      fourfold increase in the risk of patients having hearing impairment (odds ratio =
      4.15, Clodds = 1.36 to 12.63). There was no difference between the two groups in
      visual difficulties nor in marital status. Patients were approximately ten times
      more likely to be living on their own (odds ratio = 10.61; Clodds = 3.59 to
      31.33) and 16 times more likely to be considered socially isolated (odds ratio =
      16.65; Clodds = 5.39 to 51.40). There was no difference between patients and
      controls in frequency of schizophrenia-like family history. Patients were more
      likely than controls to exhibit neurological soft signs (z = 4.70; P < 0.001; Cld
      = 4.61 to 9.63). The presence of abnormal involuntary and tardive dyskinesia
      movements was associated with the use of antipsychotic medication. CONCLUSION:
      Women appear to run a greater risk of developing late paraphrenia, especially
      those who are socially isolated and present with associated hearing impairment.
      The increased presence of neurological soft signs among patients indicates that
      brain disease may be a critical factor in the development of psychotic symptoms
      in late life.

PMID- 7728367
TI  - Mental status examination of an exceptional case of longevity J. C. aged 118
      years.
AB  - BACKGROUND: The mental status examination of an extreme case of longevity, J. C.,
      aged 118 years and 9 months, is documented in order to further knowledge
      regarding profiles of morbidity in the extremely elderly. J. C. is presently
      considered to have the longest authenticated life-span in the history of the
      human species. METHOD: Neuropsychological tests were improvised taking into
      account the subject's severe perceptual deficits. The examination was carried out
      over a six-month period. A CT scan was also conducted. RESULTS: The subject's
      performance on tests of verbal memory and language fluency is comparable to that
      of persons with the same level of education in their eighties and nineties.
      Frontal lobe functions are relatively spared and there is no evidence of
      depressive symptomatology or other functional illness. Cognitive functioning was
      found to slightly improve over a six-month period. CONCLUSIONS: The subject shows
      no evidence of progressive neurological disease. A high initial level of
      intellectual ability may have constituted a protective factor.

PMID- 7728368
TI  - Symptoms of psychoses. A factor-analytic study.
AB  - BACKGROUND: The literature on the statistical analysis of symptoms of psychoses
      was limited to positive and negative symptoms in schizophrenia. The present study
      explored the relationship between positive and negative symptoms as well as
      affective symptoms in a wider category of psychotic disorders. METHOD: The
      symptoms of 584 psychiatric patients, consecutively admitted to any of the 95
      mental hospitals in Japan, were studied. They manifested at least one of the
      following: (a) delusions, (b) hallucinations, (c) formal thought disorder, (d)
      catatonic symptoms, or (e) negative (defect) symptoms. RESULTS: Factor analysis
      yielded five factors interpretable as (a) manic symptoms, (b) depressive
      symptoms, (c) negative (defect) symptoms and formal thought disorders, (d)
      positive (psychotic) symptoms, and (e) catatonic symptoms. CONCLUSION: These
      results suggest that although major symptoms seen among psychotic patients can be
      categorised into positive, negative, manic, and depressive groups, corresponding
      to current knowledge of phenomenology, catatonic symptoms constitute a discrete
      syndrome, while formal thought disorders merge into the negative syndrome.

PMID- 7728369
TI  - Effects of biperiden and amantadine on memory in medicated chronic schizophrenic
      patients. A Double-blind cross-over study.
AB  - BACKGROUND: The effects on memory of an anticholinergic (biperiden) and a
      dopaminergic (amantadine) anti-Parkinsonian agent were compared. METHOD: Twenty
      six chronically medicated schizophrenic (DSM-III-R) in-patients received
      amantadine (200 mg/day) or biperiden (4 mg/day) for two weeks in a double-blind
      cross-over design. RESULTS: Biperiden treatment was associated with significantly
      lower scores on Benton Visual Retention Test (P < 0.003) and the visual subscale
      of Wechsler Memory Scale (WMS) (P < or = 0.02), with a trend to poorer scores on
      WMS total (P = 0.086) and the digit span (P = 0.07) and logical memory (P = 0.06)
      subscales. CONCLUSIONS: In usual clinical doses, biperiden interferes with
      memory, particularly visual, more than amantadine.

PMID- 7728370
TI  - [18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic
      correlation study after treatment.
AB  - BACKGROUND: We used [18F]FDG and PET in patients with obsessive-compulsive
      disorder (OCD) to evaluate cerebral metabolic involvement before and after
      treatment with serotonin-specific reuptake inhibitors. METHOD: In 11 untreated,
      drug-free adults, regional cerebral metabolic rate for glucose (rCMRglu) was
      compared with that of 15 age-matched normal controls. RESULTS: rCMRglu values
      were significantly increased in the cingulate cortex, thalamus and
      pallidum/putamen complex. After treatment a significant improvement in obsessive
      compulsive symptoms on the Y-BOC scale (t = 3.59, P < 0.01) was associated with a
      significant bilateral decrease of metabolism in the whole cingulate cortex (P <
      0.001). Clinical and metabolic data were significantly intercorrelated (Kendall's
      tau = 0.65; P < 0.01). CONCLUSIONS: These findings indicate that OCD is
      associated with functional hyperactivity of a selected neuronal network and that
      treatment to reduce symptoms may have a selective neuromodulatory effect on
      cingulate cortex.

PMID- 7728371
TI  - The influence of Nietzsche on Freud's ideas.
AB  - BACKGROUND: The striking analogies between the ideas of Freud and Friedrich
      Nietzsche, whose works were published from one to three decades before those of
      Freud, have been commented upon, but no previous systematic correlation of the
      ideas of Nietzsche and Freud has been made. METHOD: The major works of Nietzsche
      were read, and each possible analogy to an idea later broached by Freud was
      correlated by a systematic review of his works. Any references to Nietzsche in
      Freud's writings and reported conversation were culled. RESULTS: Concepts of
      Nietzsche which are similar to those of Freud include (a) the concept of the
      unconscious mind; (b) the idea that repression pushes unacceptable feelings and
      thoughts into the unconscious and thus makes the individual emotionally more
      comfortable and effective; (c) the conception that repressed emotions and
      instinctual drives later are expressed in disguised ways (for example, hostile
      feelings and ideas may be expressed as altruistic sentiments and acts); (d) the
      concept of dreams as complex, symbolic "illusions of illusions" and dreaming
      itself as a cathartic process which has healthy properties; and (e) the
      suggestion that the projection of hostile, unconscious feelings onto others, who
      are then perceived as persecutors of the individual, is the basis of paranoid
      thinking. Some of Freud's basic terms are identical to those used by Nietzsche.
      CONCLUSION: Freud repeatedly stated that he had never read Nietzsche. Evidence
      contradicting this are his references to Nietzsche and his quotations and
      paraphrases of him, in causal conversation and his now published personal
      correspondence, as well as in his early and later writings.

PMID- 7728372
TI  - The Charles Bonnet syndrome: a large prospective study in The Netherlands. A
      study of the prevalence of the Charles Bonnet syndrome and associated factors in
      500 patients attending the University Department of Ophthalmology at Nijmegen.
AB  - BACKGROUND: The aims were to determine the prevalence of the Charles Bonnet
      syndrome (CBS) in low-vision patients and analyse possible associated ophthalmic
      and sociodemographic factors. METHOD: A semi-structured interview on visual
      hallucinations was given to 300 adult low-vision patients and 200 elderly general
      ophthalmic patients. Positive cases were examined with the Geriatric Mental State
      Schedule and the Mini Mental State Examination. Diagnostic criteria were as
      follows: complex, persistent, or repetitive visual hallucinations; full or
      partial retention of insight; no hallucinations in other modalities; and no
      delusions. Ophthalmic and sociodemographic data were gathered for all patients.
      RESULTS: The prevalence of CBS in low-vision patients was 11%. CBS was
      significantly associated with an age over 64 years and a visual acuity in the
      best eye of 0.3 or less. No significant associations with ophthalmic diagnoses,
      patient sex, marital status, or social circumstances were found. CONCLUSION: Our
      findings support association of CBS with sensory deprivation and advanced age.

PMID- 7728373
TI  - An investigation of family environmental alteration affecting short-term recovery
      from Schizophrenia in China.
AB  - BACKGROUND: It has been hypothesised that change in the family environment
      affects short-term recovery from schizophrenia. METHOD: Observation and study of
      210 schizophrenic patients who were influenced by family environmental alteration
      show that the prognosis of schizophrenia caused suddenly by family environmental
      alteration is better than that of schizophrenia caused by a persistently
      unfavourable family environment. RESULTS: Hence, we think sudden family
      environmental alterations do not cause psychorrhoea, but slow family
      environmental alteration may cause change in the mental state of patients. The
      prognosis is worse in the countryside than in the city. From the study group, we
      conclude that the first cure rate was 28%, and that 26% of patients were able to
      work. This indicates that there were no typical cases of the core pattern of
      schizophrenia, and that there was a certain potential for recovery. CONCLUSION:
      In the future, the emphasis of prevention and treatment must be placed on the
      countryside, and attention should be paid to the improvement of living and
      working conditions there, to the correct administration of patients, and to the
      improvement of recovery measures and therapy. We advocate that efforts should be
      made in the countryside to raise the national educational and cultural level.

PMID- 7728374
TI  - Asperger's syndrome and violence.

PMID- 7728375
TI  - Mental health reforms in Europe.

PMID- 7728376
TI  - ECT seizure threshold and fluoxetine.

PMID- 7728377
TI  - Discrepancies on prescribing antipsychotics.

PMID- 7728378
TI  - Language and psychiatry.

PMID- 7728380
TI  - Comparing treatments for generalised anxiety disorder.

PMID- 7728379
TI  - Psychiatrists and priests.

PMID- 7728381
TI  - General paralysis.

PMID- 7728382
TI  - The cell biology of disease.

PMID- 7728383
TI  - The Canadian Bacterial Diseases Network: a collaboration of universities,
      industry and government.

PMID- 7728384
TI  - Pathogenic strategies of the oral anaerobe, Porphyromonas gingivalis.
AB  - Adult periodontitis is a chronic inflammatory disease that affects over 49
      million people in the USA alone. Porphyromonas (formerly Bacteroides) gingivalis,
      a Gram-negative anaerobe, has a diverse repertoire of virulence factors that may
      be involved in the induction or progression of periodontitis.

PMID- 7728385
TI  - Host-range control of a retroviral disease: Friend erythroleukemia.
AB  - Since its discovery in 1957, Friend viral erythroleukemia has been the major
      model for understanding host genetic barriers to retroviral diseases and has
      facilitated the discovery of many polymorphic leukemia-control genes of mice.
      Some of these genes limit helper-virus replication, target-cell (erythroblast)
      pools or immune responses. At least one host gene appears to block the viral
      oncoprotein.

PMID- 7728386
TI  - Plant isoflavonoids, pathogens and symbionts.
AB  - It has recently been discovered that when symbiotic Rhizobium and Bradyrhizobium
      cells are outside the plant they are also exposed to the isoflavonoid
      phytoalexins that are normally associated with pathogenic infections. How the
      symbionts elicit and respond to isoflavonoids may help to define the mechanisms
      that are used by other beneficial soil microorganisms to colonize plant roots.

PMID- 7728387
TI  - Borna disease virus: implications for human neuropsychiatric illness.
AB  - The cause of Borna disease, a neurological syndrome affecting mammals and birds,
      has recently been shown to be infection with an RNA virus. Molecular genetic
      analysis suggests that Borna disease virus represents a new viral taxon. It has a
      wide host range and is tropic for specific circuits in the central nervous
      system. There is indirect evidence that links it to diseases of the human central
      nervous system.

PMID- 7728388
TI  - Tissue-culture invasion: fact or artefact?
AB  - Although widely used, tissue-culture assays cannot be exact models of the
      conditions that are met in vivo by pathogenic bacteria. However, recent studies
      of specific mutants suggest that the model is good for highly invasive bacteria,
      but it remains to be seen if this is true for weakly invasive bacteria.

PMID- 7728389
TI  - The defensive role of nonspecific lipid-transfer proteins in plants.
AB  - Plant nonspecific lipid-transfer proteins stimulate the transfer of a broad range
      of lipids between membranes in vitro. In view of their ability to inhibit
      bacterial and fungal pathogens, their distribution at high concentrations over
      exposed surfaces and in the vascular system, and the response of Ltp-gene
      expression to infection with pathogens, they are now thought to be active plant
      defense proteins.

PMID- 7728390
TI  - New therapeutic approaches in autoimmune rheumatic diseases, with special
      emphasis on rheumatoid arthritis.

PMID- 7728391
TI  - Prognostic markers of activity and damage in rheumatoid arthritis: why clinical
      trials and inception cohort studies indicate more favourable outcomes than
      studies of patients with established disease.

PMID- 7728392
TI  - Endothelium-derived haemostatic factors and the antiphospholipid syndrome.
AB  - The cause of thrombosis in the antiphospholipid syndrome (APS) is unknown. There
      have been reports of abnormalities in the antigenic levels or activity of
      endothelium-derived haemostatic factors, such as tissue-type plasminogen
      activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1); however the
      data from these studies are conflicting. We studied plasma from nine patients
      with APS; seven of them had a history of thrombosis, and three had systemic lupus
      erythematosus (SLE). We also studied nine matched control patients who had SLE
      without APS, and 14 healthy individuals. We measured t-PA, von Willebrand factor
      (vWF), anticardiolipin antibody (ACA) and anti-endothelial cell antibody (AECA)
      levels by enzyme-linked immunoassay (ELISA), PAI-1 activity by a parabolic-rate
      chromogenic assay, and lupus anticoagulant (LA) activity by a standard mixing
      test. For t-PA and PAI-1, measurements were made on morning and evening plasma
      samples. The two groups of patients did not differ significantly with respect to
      age, sex, plasma lipids or anti-inflammatory drugs. Most APS patients (7/9) but
      none of the controls were taking warfarin. Between the APS and the control
      patients no significant differences were detected in t-PA, PAI-1, vWF or AECA
      levels. When APS patients were considered alone, vWF levels correlated positively
      with IgG ACA levels (r = 0.81, P < 0.01) and negatively with platelet count (r = 
      0.68, P < 0.05). There was no correlation between levels of ACA or LA activity
      and t-PA, PAI-1 or AECA. Compared with healthy volunteers, the diurnal variation
      of t-PA and PAI-1 was blunted in the two patient groups.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7728393
TI  - Peptide transporter genes (TAP) polymorphisms and genetic susceptibility to
      rheumatoid arthritis.
AB  - The association of rheumatoid arthritis (RA) with HLA-DRB1 alleles indicates that
      at least one RA susceptibility gene is linked to the HLA class II region.
      Transporter associated with protein processing (TAP) genes, which lie upstream of
      the HLA-structural genes, may also contribute to disease susceptibility. We
      investigated polymorphisms of the peptide transporter genes, TAP 1 and TAP 2, by
      PCR-ASO hybridization techniques in 82 RA patients and 66 control individuals.
      Although there was a suggestion of linkage between some TAP polymorphisms and RA,
      these seem to be dependent on HLA-DRB1*04, since these positive associations
      disappeared when HLA-DRB1*04 positive RA patients and controls were compared.
      Furthermore, no particular TAP allele or haplotype was associated with any
      clinical or immunological subgroup of RA. We conclude that the TAP genes do not
      have a major influence on susceptibility to RA in the European Caucasian
      population.

PMID- 7728394
TI  - Heterogeneity of disease phenotype in monozygotic twins concordant for rheumatoid
      arthritis.
AB  - The objective of the study was to investigate the genetic contribution to the
      clinical expression of rheumatoid arthritis (RA) by comparison of disease
      features in RA-concordant monozygotic (MZ) twin pairs. Fourteen RA-concordant MZ
      twin pairs recruited from a nation-wide study were examined to determine the
      degree of similarity in: (a) age of disease onset; (b) pattern of joint
      involvement; (c) pattern of extra-articular disease; (d) toxic reactions to
      drugs; (e) disease course; and (f) serology for rheumatoid factor (RF) and
      antinuclear antibody. There was considerable within-pair diversity in the
      variables studied. Some similarity within twin pairs was observed for the ages at
      disease onset (R = 0.63), presence of erosive changes (kappa = 0.61) and the
      presence of IgM RF (R = 0.87). No important similarity was seen, however, in the
      pattern of joint involvement, the occurrence of extra-articular disease, adverse
      drugs reactions, clinical disease course and reported disability level. There is
      heterogeneity in the genetic contribution to the clinical expression of RA. The
      overall lack of similarity for the majority of clinical variables indicates the
      importance of non-genetic factors on the expression of disease.

PMID- 7728395
TI  - Relative contributions of HLA-DQA and complement C4A loci in determining
      susceptibility to systemic lupus erythematosus.
AB  - The objective of this study was to reassess the role of C4A null alleles in
      systemic lupus erythematosus (SLE) susceptibility after taking into account the
      association of DQA*0501 with this disease. The frequency of C4A null alleles in
      82 SLE patients and 59 controls was determined using both immunofixation and a
      TaqI RFLP method. HLA-DQA and DQB alleles were identified by sequence-specific
      oligonucleotide typing. Empirical logistic analysis was used to assess the
      interactive effects of C4 and DQA alleles. It was found that the strongest
      association with SLE was for the combination of DQA*0501 and C4A*Q0 [odds ratio
      (OR) = 5.4, 95% confidence interval (CI) 2.5-11.7]. Both DQA*0501 (P = 0.02) and
      C4A*Q0 (P = 0.03) appeared to have significant individual effects on SLE
      susceptibility, with a significant statistical interaction between the two loci
      (P = 0.01). However, when anti-La antibody negative patients were examined only
      C4A*Q0 had a significant individual effect (P = 0.04). A significant statistical
      interaction between DQA*0501 and C4A*Q0 was again detected (P = 0.02). These
      results support the hypothesis that susceptibility to SLE is influenced by
      several genes with differing functions: HLA-DQA*0501 may predispose to
      autoantibody formation while C4A*Q0 impairs immune complex clearance.

PMID- 7728396
TI  - Interferon-gamma and epithelial cell activation in Sjogren's syndrome.
AB  - We have examined the hypothesis that interferon-gamma (IFN-gamma) and its
      interaction with epithelium may play a role in the perpetuation of inflammation
      in Sjogren's syndrome (SS). Labial salivary gland primary cell cultures from 16
      patients with primary SS (pSS) and eight cultures from patients with SS symptoms
      but histologically normal biopsies were examined for expression of HLA-DR and
      cytoplasmic La (SS-B). Epithelial HLA-DR expression was found in 80% of cultures
      from pSS patients and 38% of those from patients not fulfilling diagnostic
      criteria. Cytoplasmic La was detected in 50 and 38% of cultures, respectively.
      Treatment of 14 of the cultures with IFN-gamma increased HLA-SR and cytoplasmic
      La expression above that of untreated cultures. Depletion of IFN-gamma using
      neutralizing antibody had the reverse effect. These findings suggest that the
      perpetuation of chronic inflammation of pSS may be due to the induction of HLA-DR
      and La antigen expression on epithelial cells by IFN-gamma.

PMID- 7728397
TI  - T-cell clonality in synovial fluid from rheumatoid joints before and after
      culture in interleukin-2.
AB  - T-cell receptor (TCR) gamma gene rearrangements which have been amplified in
      polymerase chain reactions (PCRs) and analysed by high resolution polyacrylamide
      gel electrophoresis have been used to investigate the clonal diversity of T-cells
      in joint effusions from 16 patients with rheumatoid arthritis, one with systemic
      lupus erythematosus and one with psoriatic arthropathy. Polyclonality was found
      in every case but an oligoclonal subset of dominant rearrangements was also
      demonstrated in all but the patient with psoriasis. Marked changes in the
      relative preponderance of the various clonotypes were observed in 29 of 48 paired
      tests from 12 cases before and after culture in media containing interleukin-2
      (IL-2) showing that SF mononuclear cells cultured in vitro with IL-2 are not
      representative of those present in vivo.

PMID- 7728398
TI  - Rheumatoid factor associated with a secretory component in rheumatoid arthritis.
AB  - The authors' objective was to study the serum secretory immunoglobulin A (S-IgA)
      concentration and the presence of rheumatoid factor (RF) complexed with a
      secretory component (SC) in rheumatoid arthritis (RA). Sixty-three RA patients
      were studied. There were 49 healthy subjects in the control group. The S-IgA
      concentration and the presence of IgA isotype RF were determined by ELISA in the
      serum. The presence of SC complexed to RF (SC-RF) was studied by a sandwich-type
      enzyme-linked immunosorbent assay with an antibody against the SC used to capture
      S-immunoglobulin, and associated anti-globulin activity was revealed with a
      peroxidase-conjugated human IgG Fc fragment. We observed a significant increase
      in S-IgA in RA (mean 76.8 micrograms/ml +/- 152.9 S.D.), as compared to controls
      (mean 13.6 micrograms/ml +/- 11.9 S.D.) (P < 0.01). Forty-one per cent of RA
      patients presented a S-IgA concentration above the upper threshold, but we did
      not observe any association with disease activity. S-IgA concentration was
      correlated with the presence of IgA-RF. Twenty-seven RA patients had a positive
      SC-RF versus one in the control group (P < 0.01). The presence of SC-RF was
      associated with an increased S-IgA concentration (P < 0.0001), and the presence
      of RF-IgA (P < 0.002). However, no association with disease activity was noted.
      Our study showed that serum S-IgA was increased in RA, and that part of the RF
      were complexed with SC. These results suggest contribution of mucosal lymphocytes
      in the pathogenesis of RA.

PMID- 7728399
TI  - The effect of liposomally conjugated methotrexate upon mediator release from
      human peripheral blood monocytes.
AB  - The ability of methotrexate (MTX) and a liposomal preparation containing a
      lipophilic conjugate of methotrexate (MTX-LIPO) to modulate pro-inflammatory
      mediator release from lipopolysaccharide-stimulated human peripheral blood
      monocytes was investigated. At non-toxic concentrations MTX-LIPO (10 micrograms
      MTX per 250 micrograms lipid) was a potent inhibitor of both IL-1 beta and TNF
      release resulting in 70.07 +/- 2.3% and 59.19 +/- 2.36% (mean +/- S.E.M.)
      inhibition, respectively, whereas empty liposomes (E-LIPO; 250 micrograms
      lipid/well) of the same lipid composition and free MTX (up to 100
      micrograms/well) had no effect on either mediator.

PMID- 7728400
TI  - Continuing occurrence of eosinophilia myalgia syndrome in Canada.
AB  - Eosinophilia myalgia syndrome (EMS), was defined by the Centers for Disease
      Control (CDC) as eosinophilia > 1000 mm3 and incapacitating myalgia without
      infection or neoplasm. Studies suggested that use of L-tryptophan (L-T), was a
      risk factor. We conducted a pharmacoepidemiological survey in Canada where access
      to L-T is limited. Using the active surveillance method, a 100% sample of
      potentially involved specialists and a 15% sample of family physicians from
      Ontario and Quebec were surveyed regarding treatment of patients with severe
      myalgia within the past year. Follow-up amplified clinical and laboratory
      information. Overall response rates were 61.4%. Thirty-eight per cent of
      respondents reported at least one patient. Of 6423 patients assessed, 19
      'definite' and 25 'possible' EMS cases were identified. Information from
      physicians did not suggest use of L-T in patients with definite or possible EMS.
      It was considered that the cases found an underestimate of the incidence of EMS.
      Its continuing occurrence in Canada brings causal interpretations of earlier
      studies into question.

PMID- 7728401
TI  - The prevalence of rheumatoid arthritis in affluent and poor urban communities of
      Pakistan.
AB  - Using previously applied methods a survey of joint symptoms was undertaken among
      4232 adults, evenly distributed between affluent and poor areas of Karachi,
      Pakistan. Only six cases of definite rheumatoid arthritis (RA) (1958 ARA
      criteria) were identified in the 245 persons who complained of joint problems of
      at least 4 weeks duration. The prevalence was 0.9 [confidence interval (CI) 0.21
      3.61] and 1.98 (CI 0.55-5.1) per thousand in the poor and affluent districts,
      respectively. These were substantially less than prevalence rates reported in the
      West but were similar to figures derived from other developing countries. There
      was no obvious impact of current living standards on the findings. The relative
      paucity of older female subjects in both the affluent and poor communities may
      account at least in part for the low rates observed. The infrequency of
      rheumatoid nodules in Southern Asians with RA illustrates the difficulty of
      applying existing diagnostic criteria to this community.

PMID- 7728402
TI  - The occurrence, nature and distribution of flares in a cohort of patients with
      systemic lupus erythematosus: a rheumatological view.
AB  - This study examines the occurrence, nature and distribution of disease flares in
      systemic lupus erythematosus (SLE) according to organ involvement. One-hundred
      and-fourteen patients were seen in the Lupus Clinic of the Bloomsbury
      Rheumatology Unit over a 3-yr period. At each visit a data sheet was completed to
      assess their disease activity in eight separate organs/systems according to the
      British Isles Lupus Assessment Group (BILAG) activity index. This information was
      entered into a computer and a score for each organ system was obtained. The
      record of each individual patient was examined to identify flares in the
      individual organs; 458 flares occurred in 107 patients. The majority of patients
      (69%) experienced more than one flare during the study period. Fifty-four per
      cent of patients had flares in more than one system simultaneously, but the
      majority (70%) of flares involved only one system. The most severe organ
      involvement (A score) was most commonly observed in the musculoskeletal system,
      whereas severe renal disease occurred only three times. These results indicate
      that although SLE is a multisystem disease, the flares that occur tend to be
      confined to one system at a time. Further, these results demonstrate that in our
      rheumatology practice the most common 'A' flare observed was severe polyarthritis
      (A score in musculoskeletal).

PMID- 7728403
TI  - Epidemiology and mortality in 220 patients with polymyalgia rheumatica.
AB  - Between 1985 and 1987 a total of 521 people underwent temporal artery biopsy with
      no histological evidence of arteritis in Goteborg, Sweden. Two-hundred-and-twenty
      people were diagnosed as having polymyalgia rheumatica (PMR). Among the patients
      without PMR 30% had rheumatic, 17% malignant and 14% infectious disorders. The
      annual incidence of PMR with negative biopsy was 17/100,000 and for the
      population over 50 yr it was 50/100,000. We found an increased mortality in
      vascular diseases among men with PMR in the first 2 yr after diagnosis with 13
      observed deaths compared to the expected six (P < 0.01). There was also a
      tendency toward an increased mortality among the women with 16 observed deaths
      compared to the expected 11 (not statistically significant). The mortality in
      malignant diseases was not increased.

PMID- 7728404
TI  - Small bowel bacterial overgrowth in systemic sclerosis: detection using direct
      and indirect methods and treatment outcome.
AB  - Twenty-four patients with proven systemic sclerosis and with symptoms suggestive
      of malabsorption (i.e. chronic diarrhoea and weight loss) were investigated for
      small bowel bacterial overgrowth. Of the patients selected, six were suffering
      from the diffuse form of the disease. Jejunal aspiration was performed in all
      patients, and in nine normal volunteers. A specially designed double-lumen
      sterile catheter was used for this purpose and was introduced via a gastroscope.
      Twenty of these patients underwent a glucose hydrogen breath test. Eight patients
      (33%) had significant bacterial counts: > 10(5) colony forming units per ml
      (cfu/ml) of jejunal fluid. Less than 10(2) cfu/ml were found in the jejunal fluid
      from the nine control subjects. Glucose hydrogen breath testing was positive in
      seven patients, all of whom had significant jejunal bacterial growth. Diarrhoea
      rather than weight loss was shown to be the symptom which correlated best with
      the presence of bacterial overgrowth. Ciprofloxacin was used in six patients
      whose diarrhoeal symptoms ceased dramatically within 48 h of commencing the
      antibiotic. Trimethoprim produced a partial response despite bacterial
      sensitivity. A disadvantage of the hydrogen breath test is that subsequent
      antibacterial therapy cannot be specific, as bacterial species, antibiotic
      sensitivity and resistance are unknown. Systemic sclerosis involving the small
      intestine in the past has been said to more prevalent in patients with diffuse
      disease, whereas this study showed a preponderance of patients with long-standing
      limited cutaneous systemic sclerosis and small bowel involvement.

PMID- 7728405
TI  - The effects of elemental diet and subsequent food reintroduction on rheumatoid
      arthritis.
AB  - The role of diet in rheumatoid arthritis (RA) remains controversial and there
      have been no controlled studies on the use of elemental diet in the treatment of
      RA. Elemental diet is an hypoallergenic protein-free artificial diet consisting
      of essential amino acids, glucose, trace elements and vitamins. This study was
      carried out to assess the role of elemental diet and subsequent food
      reintroduction in RA. Elemental diet (E028) (and a small number of foods) was
      given to 24 patients with definite RA in order to induce a remission and then
      foods were gradually introduced. Where a food was suspected of causing symptoms
      it was removed from the diet. Twenty-three control patients supplemented their
      usual diet with E028. After the elemental diet there was a statistically
      significant improvement in the diet group in grip strength (P = 0.008) and
      Ritchie score (P = 0.006) but not in ESR, CRP, thermographic joint score or
      functional score. The diet group lost more weight than the control group and this
      correlated with the improvement in grip strength. This improvement was not
      present following food reintroduction. As the improvements took place in more
      subjective disease parameters and because of the difficulties in adequately
      blinding studies of diet in arthritis, a placebo effect must be considered. There
      was a high default rate, only 38% of those patients originally enrolled completed
      the study. In conclusion, this study shows that elemental diet can cause an
      improvement in a number of disease parameters in RA but this is not sustained by
      an individualized diet. It also illustrates some of the difficulties involved in
      the study of diet in arthritis.

PMID- 7728406
TI  - Surgery to the wrist joint.

PMID- 7728407
TI  - 6th European Regional Conference of Rehabilitation International.

PMID- 7728408
TI  - Type 1 cryoglobulinaemia associated with a thymic tumour: successful treatment
      with plasma exchange.
AB  - Thymic tumours are associated with a wide range of autoimmune and haematological
      disorders, notably myasthenia gravis, red cell aplasia, and systemic lupus
      erythematosus. An association with cryoglobulinaemia has only once been reported
      previously. In this report we describe a 60-yr-old male patient with a spindle
      cell thymoma, treated surgically, who also had type 1 cryoglobulinaemia, with
      severe peripheral circulatory impairment with digital ulceration and a
      mononeutitis multiplex. The patient has been successfully treated with
      prednisolone, immunosuppression and plasma exchange.

PMID- 7728409
TI  - Non-Hodgkin's lymphoma and polyarthritis.

PMID- 7728410
TI  - Pseudogout masking brucellar arthritis.

PMID- 7728411
TI  - Generalized pruritus in the rheumatoid patient--consider all possible causes.

PMID- 7728412
TI  - Transient regional osteoporosis of the hip.

PMID- 7728413
TI  - Role of thromboxane A2 and platelet-activating factor in allergic
      bronchoconstriction in guinea pig airway in vivo.
AB  - Membrane-derived lipid mediators have been considered to play a major role in
      pathogenesis of bronchial asthma. However, the importance of and the interactions
      among each mediator are still unclear. We examined the role of thromboxane A2
      (TXA2) and platelet-activating factor (PAF) in immediate asthmatic response (IAR)
      and interactions between these lipid mediators in guinea pig airway in vivo using
      a specific TXA2 antagonist S-1452 and a specific PAF antagonist Y-24180. We
      confirmed the activity of each antagonist, as S-1452 and Y-24180 significantly
      and dose-dependently inhibited bronchoconstriction induced by respective agonist
      inhalation. S-1452 inhibited IAR but Y-24180 did not, indicating that TXA2 plays
      a major role in IAR but PAF does not. S-1452 significantly inhibited PAF-induced
      bronchoconstriction but Y-24180 did not inhibit synthesized TXA2 (STA2)-induced
      bronchoconstriction, showing that the bronchoconstrictive effect of PAF is at
      least in part dependent on secondarily released TXA2, but TXA2 does not induce
      PAF production.

PMID- 7728414
TI  - PAF and human cardiovascular disorders.

PMID- 7728415
TI  - Acyl-CoA synthetase activity depends on the phospholipid composition of rat liver
      plasma membranes.
AB  - The dependence of acyl-CoA synthetase on the lipid composition of rat liver
      plasma membranes has been investigated. For this purpose the composition of the
      membranes was modified by incorporation of different phospholipids in the
      presence of partially purified lipid transfer proteins. Another approach to the
      modification of the membrane phospholipid composition was treatment with
      exogenous phospholipase C and subsequent enrichment with different phospholipids.
      The experiments performed in vitro indicated that the presence of certain
      phospholipids such as phosphatidylnositol, phosphatidylethanolamine,
      phosphatidylglycerol and phosphatidylserine was essential for the activation of
      long chain fatty acids by acyl-CoA synthetase. However, some differences were
      observed when oleate and palmitate were used as substrates. Sphingomyelin was
      found to inhibit this activity especially when oleic acid served as substrate. In
      addition, we tried to modify in vivo the membrane lipid composition by treatment
      with D-galactosamine, which is known to induce acute hepatitis and cause
      biochemical and biophysical alterations in liver membranes. The results thus
      obtained confirmed the idea that the augmentation of the membrane lipids and
      especially of PI, PE and PG was accompanied by acyl-CoA synthetase activation.
      The presence of two different enzymes, activating the saturated and unsaturated
      fatty acids is discussed.

PMID- 7728416
TI  - Inhibition of prostaglandin E2-responsive adenylyl cyclase in embryonal human
      kidney 293 cells by phorbol esters.
AB  - A clonal primary embryonal human kidney cell line, 293, increased cAMP production
      in response to prostaglandin E2 (PGE2) (0.02-2 microM). The purpose of this study
      was to show the effects of tumor-promoting phorbol esters (e.g., 4 beta-phorbol
      12-myristate 13-acetate, PMA) on PGE2-stimulated cAMP production. Pretreatment
      with PMA (0.2-200 nM) for 30 min markedly reduced PGE2-stimulated cAMP production
      in the presence of 0.5 mM isobutylmethylxanthine. The reduction by PMA was dose-
      and time-dependent. PMA seems to attenuate the increase in cAMP accumulation
      elicited by PGE2 primarily, if not entirely, by inhibiting adenylyl cyclase
      activity, since we were unable to demonstrate an effect of PMA on the degradation
      half-life of cAMP in intact 293 cells. The action of PMA had some specificity for
      the agonist used; thus, PMA inhibited PGE2-activated adenylyl cyclase but had no
      effect on the forskolin-activated enzyme. Co-pretreatment with PMA and H-7, an
      inhibitor of protein kinase C (PKC), partially prevented the PMA-induced
      attenuation of the PGE2-stimulated cAMP accumulation, and 1-oleoyl-2
      acetylglycerol, a synthetic diacylglycerol analog, partially mimicked the PMA
      action. Thus, PMA appeared to decrease cAMP production by a PKC-mediated
      mechanism, inhibiting adenylyl cyclase activity at a point other than the
      catalytic subunit of the enzyme in the kidney 293 cell line.

PMID- 7728417
TI  - Detection of 4-hydroxynonenal (HNE) as a physiological component in human plasma.
AB  - 4-Hydroxynonenal (HNE) is a major aldehydic product formed by peroxidation of
      omega 6-unsaturated fatty acids and is regarded as a specific marker of lipid
      peroxidation. In this paper we demonstrate that there is a physiological steady
      state concentration of HNE in human venous blood plasma. For the quantitative
      determination of HNE a modified version of an existing, but tedious and time
      consuming HPLC method was developed. The extraction of aldehydic hydrazones from
      plasma was performed using an Extrelut column and the separation step by thin
      layer chromatography was replaced by column chromatography on silica gel. The
      concentration of HNE in human blood plasma was in the same range as the
      concentration that was found to inhibit the proliferation of cells of the
      peripheral tissues, i.e., endothelial cells and fibroblasts in vitro. In an
      experiment with reduced peripheral blood flow a temporary significant increase of
      HNE was observed during reperfusion. It was concluded that lipid peroxidation
      occurs in peripheral tissues of humans following temporary congestion of venous
      blood flow.

PMID- 7728418
TI  - Influence of polyunsaturated fatty acids on lipid metabolism in human blood
      mononuclear cells and early biochemical events associated with lymphocyte
      activation.
AB  - n-3 and n-6 polyunsaturated fatty acids are involved in the regulation of the
      immune response. Although different hypotheses related to modifications of
      arachidonic acid metabolism or alterations at the level of the cell membrane have
      been put forward to explain their suppressive effect on the lymphocyte growth,
      their mechanism of action remains largely unknown. Cyclic nucleotide
      phosphodiesterase (PDE) has been shown to be an important target involved in the
      control of lymphocyte proliferation. The present study aimed to determine whether
      in vitro addition of a physiological concentration (5 microM) of n-6 (20:3n-6) or
      n-3 (18:4n-3, 20:5n-3, 22:6n-3) fatty acids to human peripheral blood mononuclear
      cells (PBMC) was able to alter the PDE activity of these cells, and especially
      the PDE increase in response to Con A stimulation. Pretreatment of human PBMC for
      a short period of time (90 min) with 5 microM of either 20:3n-6, 20:5n-3 or 22:6n
      3 was sufficient to induce a significant enrichment of cellular phospholipids in
      the corresponding fatty acid, whereas 18:4n-3 was poorly incorporated. Either
      fatty acid significantly increased both cAMP- and cGMP-PDE activities in the
      cytosolic compartment, the particulate PDE activities being less sensitive to
      their stimulatory effect. In contrast, they significantly lowered the PDE
      increase to Con A stimulation. Except 20:5 n-3, the three other fatty acids did
      not alter significantly the basal or Con A-induced oxygenated metabolism of
      arachidonic acid (AA), appreciated by the measurement of radioactive eicosanoids
      formed in [3H]AA-labelled cells. Furthermore, only 20:5n-3 significantly
      inhibited the lymphoproliferative response to Con A, whereas 16:0, 18:0, 18:1n-9,
      20:3n-6 and 20:4n-6 were inactive. The inhibitory effect was not prevented by
      antioxidant vitamins C and E. The present results suggest that the lymphocyte
      growth suppressive effect of 20:5n-3 20:5n-3 is very likely to be independent on
      both the cAMP system and eicosanoid synthesis, and does not seem to involve their
      conversion to peroxidised products.

PMID- 7728419
TI  - Phosphoinositide hydrolysis by phospholipase C modulated by multivalent cations
      La(3+), Al(3+), neomycin, polyamines, and melittin.
AB  - Second messenger production from phosphoinositide hydrolysis is regulated by
      different pathways, such as G-proteins or tyrosine phosphorylation of
      phosphoinositide phospholipase C (PI-PLC). Another means of altering the activity
      of PI-PLC is through cation interaction with the phosphoinositide substrate. A
      variety of organic and inorganic multi-valent cations were examined for their
      effects on the activity of purified PI-PLC delta. Surprisingly, the cations
      produced both stimulation and inhibition of PI-PLC catalyzed phosphoinositide
      hydrolysis, depending on the substrate and the ion to phosphoinositide
      stoichiometry. These data support the hypothesis that ionic complexes with
      phosphoinositides may alter their hydrolysis by PI-PLC.

PMID- 7728420
TI  - Subgroup analyses: primary and secondary.

PMID- 7728421
TI  - Two weeks post-death report by parents of siblings' grieving experience.
AB  - Nurses who work with children and families need to be aware of the impact that
      the death of sibling has on children. Although many children have experienced
      losses, the loss of a sibling of course has a tremendous affect. Nurses must
      educate parents and children about death and the affect on the entire family.
      Siblings should be involved in the communication about the impending death and in
      the funeral arrangements. Open communication between the dying child, the
      siblings and the parents is very important. Young children will have different
      needs than older children because of their difficulty in understanding the
      finality of death. It is natural for parents to try to protect their children
      from unpleasant experiences such as death and dying. Research supports the dying
      process including the funeral. Children and their families need support through
      out the dying experience including follow up after the actual death. They need to
      be assured that their feelings and actions are common to others that have
      suffered a significant loss.

PMID- 7728422
TI  - Relationship between patterns of infant temperament, child behavior ratings, and
      interactions during toddlerhood.
AB  - This longitudinal study examined the relationship of temperament ratings during
      infancy, subsequent child behavior problems, and mother-child interaction. The
      authors considered the effect of change in mothers' perceptions of their infants'
      temperament during infancy (e.g., from easy to difficult or from difficult to
      easy) on subsequent developmental outcomes. Data from a predominantly middle
      class Caucasian sample of 49 mother-child dyads are presented here. Findings
      revealed that children with discontinuities in 4 and 8-month ratings on the
      Revised Infant Temperament Questionnaire (e.g, Easy/Difficult or Difficult/Easy)
      had significantly higher problem and intensity scores on the Eyberg Child
      Behavior Inventory than those with stable temperament ratings (Carey & McDevitt,
      1978a). No significant differences were found in maternal behaviors between
      mothers of children rated easy or difficult at 4 or 8 months. These results
      suggest that continuity of infant temperament ratings is an important factor for
      consideration in subsequent maternal identification of toddler behavior problems,
      and that difficult temperament alone may not predict such problems.

PMID- 7728423
TI  - The verdict is in: seclusion is out.

PMID- 7728424
TI  - The use of a playroom as a nursing intervention with the early adolescent age
      group.
AB  - Most interventions for adolescents have relied upon a group format. Early-age
      adolescents who demonstrate hyperactivity, cognitive impairment, or regressive
      behavior often find the "talk" format of groups difficult. This article advocates
      the use of a classic playroom equipped with materials for the early adolescent as
      an adjunct intervention to individual and milieu therapy modalities. Two case
      examples illustrate the use of a playroom as an intervention.

PMID- 7728425
TI  - The use of methylphenidate in children with attention-deficit hyperactivity
      disorder.

PMID- 7728426
TI  - The heat is on.

PMID- 7728427
TI  - Transitional objects: a review of the literature.
AB  - The author provides a historical overview of the literature on the topic of
      transitional objects and transitional phenomena. Specific attention is given to
      the literature that has focused on: (a) the meaning and significance of the
      concept, (b) its relation to psychological development, and (c) an exploration of
      cultural and gender differences among users of the transitional object.
      Implications for therapy and suggestions for further research in this area are
      also be addressed.

PMID- 7728428
TI  - [Effect of working shift timing and different workload on development of fatigue
      in workers].
AB  - The authors studied functional changes of central nervous and cardiovascular
      systems among operators having variable work strain (airlines dispatchers,
      operators of robot complexes, TV operators) and changeable duration of working
      shift (8 and 12 hours). Analysis of the materials considered work strain in the
      occupational groups (I, II and III degrees of strain) and duration of the working
      shift. The results proved that the fatigue degree depends on the work strain
      degree and duration of the working shift, so prophylaxis and normal work duration
      could be set.

PMID- 7728429
TI  - [Human factor and occupational standardization].
AB  - Regulation of work is a complex social and biologic task including two
      independent but associated aspects. The first one is technical and economic
      regulation orientated to work results, and the second one, ergonomic, considers
      influence of work on human body. Regulation of work and consumption is based on a
      compromise between those two aspects. Ergonomic regulation covers such
      characteristics of work, as load and intensity, jeopardy and hazard, lack of
      attractiveness and prestige, therefore 3 subunits of ergonomic regulation are
      physiologic, hygienic and psychologic. Physiologic regulation is designed to set
      maximal allowable load (by restricting extremely high and low values which harm
      health) and optimum one (to improve physical and psychic abilities, activate
      resources for functional efforts).

PMID- 7728430
TI  - [Current problems of physiology and pathophysiology of mental work].
AB  - Research concerning physiology and pathophysiology of mental work includes such
      topical spheres as mechanisms maintaining capacity and reliability of the work,
      adaptation and stress in exposure to occupational and social factors, psychologic
      and physiologic functioning in premorbid conditions and chronic diseases,
      physiologic regulation of work, forecast and correction of health and capacity
      for work. These problems of mental work physiology could not be solved without
      thorough studies in prophylaxis and clinical medicine, without cooperative
      activities of scientists and skilled professionals in many countries.

PMID- 7728431
TI  - [Occupational physiology, its achievements and trends in the contemporary
      industry].
AB  - The main task of research in industrial hygiene is to supply various occupations
      with prophylaxis against overstrain and its consequences. The authors studied
      physiologic mechanisms underlying overstrain development and consequences,
      revealed dependences of overstrain degree on work parameters. That helped to
      elaborate efficient measures preventing overstrain and diseases characteristic
      for some occupations. Some scientific and prophylactic items of research for
      oncoming years were defined.

PMID- 7728432
TI  - [Physiologic evaluation of permissible work timing at the video display].
AB  - The studies covered changes in functional state of 42 programmers working at VGA.
      All the examinees reported subjective evaluation of fatigue and variational
      pulsometry before and after the work at VGA, those who worked at the display for
      3 hours underwent blood pressure and pulse rate measurements (with subsequent
      calculation of several hemodynamic parameters) before and after the work. The
      researchers applied Major Components Method to obtain some integral parameters.
      The obtained values described initial state of cardiovascular system and changes
      in autocorellation of some BCG intervals. The fatigue was proved to occur by the
      end of the second working hour, and by the end of the third hour the examines
      demonstrated unfavorable changes of functional state (depression of heart
      activities and increased blood pressure). Only those who worked over 4 hours
      reported discomfort, so functional disorders appear earlier, than individuals
      detect them.

PMID- 7728433
TI  - [Work capacity of the operators of chemical industry and its effect on motor
      activity].
AB  - Motor activity, energy metabolism, work productivity, functioning and regulation
      of cardiovascular system were examined in machine operators working at 2 chemical
      enterprises. The energy loss within the shift appeared to vary from 800 to 1200
      kcal, that within the day--from 2,500 to 2,900 kcal. The examinees demonstrate
      lack of physical training that affects the functioning of cardiovascular system.
      However, the study found no correlation between the Physical State Index and the
      work productivity. The elderly operators show higher work productivity associated
      with more noticeable lack of physical training. The authors conclude also that
      daily amount of physical load should be considered in evaluation of low physical
      training impact.

PMID- 7728434
TI  - [Physiologic characteristics of work capacity using models of nervous and high
      tension job].
AB  - The experiments enabled to design a physiologic curve showing sensomotor
      performance and therefore functional state of the examinees' central nervous
      system in all periods of performing the tasks. Considering correlations between
      the periods and phases, quantitative analysis of the curve defines physiologic
      features and mechanisms underlying performance changes during work associated
      with mental strain.

PMID- 7728435
TI  - [Physiologic and hygienic evaluation of the job and health status in workers of
      shoe factory].
AB  - The article contains materials on complex physiologic and hygienic evaluation of
      work performed by various shoe-making occupations. The main occupational hazards
      are air pollution with chemicals, noise, vibration, considerable physical and
      psychophysiologic strain, visual exertion, inadequate working posture. The
      workers demonstrated fatigue of the main body functions during the shift.
      Diseases of locomotion and nervous system appeared to be prevalent among the shoe
      makers. The complex of prophylactic measures is elaborated.

PMID- 7728436
TI  - [Corrections of functional status of vessels of the legs as a prevention and
      optimization of the weavers job].
AB  - The physiologic studies of weavers' productivity proved that pneumatic
      hydromassage of the legs results in significant relief of unfavorable changes in
      vessels of the lower limbs. Therefore, the work performance and productivity
      increase.

PMID- 7728437
TI  - [Changes of tension in workers on different shifts].

PMID- 7728438
TI  - [Characteristics of super-slow bioelectric reactions in shift workers].

PMID- 7728439
TI  - [Hormonal status evaluation in the production managers for the diagnosis of their
      work intensity].

PMID- 7728440
TI  - [Occupational characteristics of the Criminal Police officers].

PMID- 7728441
TI  - [Electromyography of the neuromuscular fatigue caused by posture of drivers of
      the loading machines].
AB  - The authors studied strain degree and fatigue severity in long-standing
      inconvenient postures at work of automobile loader operators. Those workers
      perform tasks in various postures due to the design of automobile loaders.
      Compared to standardized postures, long-standing inconvenient ones of automobile
      loader operators, characterized by left turn of corpse, appear to result in
      marked overstrain and significant fatigue of neuromuscular apparatus. If specific
      prophylaxis is absent, the work in such postures could induce considerable
      fatigue.

PMID- 7728442
TI  - Skill mix fixed.

PMID- 7728443
TI  - Life and death in the opportunity arena.

PMID- 7728444
TI  - Take control of your budget.

PMID- 7728445
TI  - Many happy returners?

PMID- 7728446
TI  - Test drive an audit.

PMID- 7728448
TI  - Disappointing appointments.

PMID- 7728447
TI  - Where the reforms do and don't deliver.

PMID- 7728449
TI  - Pathway to the heart of care quality.

PMID- 7728450
TI  - Evolved to involve.

PMID- 7728451
TI  - Yet another threatened nurse staffing crisis.

PMID- 7728452
TI  - Recruitment crisis returns.

PMID- 7728453
TI  - The bank manager's account.

PMID- 7728454
TI  - 2001 commission impossible?

PMID- 7728456
TI  - Career off the path.

PMID- 7728455
TI  - Teachers play the triangle.

PMID- 7728457
TI  - Merger or murder?

PMID- 7728458
TI  - Clinical supervision.

PMID- 7728459
TI  - Wage war on your budget.

PMID- 7728460
TI  - Casuals stay in fashion.

PMID- 7728461
TI  - NHS purchaser arrangements.

PMID- 7728463
TI  - Control your consultants.

PMID- 7728462
TI  - Executive execution.

PMID- 7728464
TI  - Nurse practitioners: professional push or patient pull?

PMID- 7728465
TI  - Windows through the glass ceiling.

PMID- 7728466
TI  - Grow your own career (because no one else is going to do it for you...).

PMID- 7728467
TI  - PREPare for the next century.

PMID- 7728469
TI  - A&E--still youthless?

PMID- 7728468
TI  - Value added tacks.

PMID- 7728470
TI  - Negotiating for nursing homes.

PMID- 7728471
TI  - Managing chaos.

PMID- 7728472
TI  - Continuing care continuing where?

PMID- 7728473
TI  - Local difficulties.

PMID- 7728474
TI  - Mohs surgery and malignant melanoma.

PMID- 7728475
TI  - Stump the experts. Cutaneous bronchogenic cyst.

PMID- 7728476
TI  - The prognosis and treatment of true local cutaneous recurrent malignant melanoma.
AB  - BACKGROUND: The prognosis and treatment of true local cutaneous recurrent
      malignant melanoma is presently unknown. We define this entity as melanoma
      bearing an in situ component that recurs contiguous with the scar of the primary
      excision. Although previously uncommon, the incidence of true local recurrent
      melanoma may rise due to the recent use of more narrow margins for excision of
      thin primary melanoma. OBJECTIVE: We hypothesized that there is a difference in
      prognosis between true local cutaneous recurrent melanoma versus local recurrence
      from satellite or in-transit metastases. Also, we defined guidelines for the
      surgical management of true local cutaneous recurrent melanoma. METHODS: We
      calculated the surgical margin necessary to reach a tumor-free plane using Mohs
      surgery in 50 patients with true local recurrent melanoma. Patient survival was
      determined by the Kaplan-Meier method. RESULTS: Seventy-six percent of the tumors
      were completely excised using a margin of less than 1 cm. However, a margin of up
      to 2 cm was required to successfully treat all 50 patients. Thicker tumors did
      require significantly larger margins. The Kaplan-Meier 5-year overall and
      melanoma survival rates were 89% and 98%, respectively. The 5-year disease-free
      survival rate was 66%. CONCLUSION: The prognosis of true local recurrent melanoma
      is related to tumor thickness. We recommend full-thickness excision of the entire
      old scar including a 2-cm margin or Mohs surgery if a narrower margin of
      resection is desired.

PMID- 7728477
TI  - Allergic reactions to tattoo pigment after laser treatment.
AB  - BACKGROUND: Cutaneous allergic reactions to pigments found in tattoos are not
      infrequent. Cinnabar (mercuric sulfide) is the most common cause of allergic
      reactions in tattoos and is probably related to a cell-mediated (delayed)
      hypersensitivity reaction. OBJECTIVE: The purpose of these case presentations is
      to describe a previously unreported complication of tattoo removal with two Q
      switched lasers. RESULTS: Two patients without prior histories of skin disease
      experienced localized as well as widespread allergic reactions after treatment of
      their tattoos with two Q-switched lasers. CONCLUSION: The Q-switched ruby and
      neodymium:yttrium-aluminum-garnet lasers target intracellular tattoo pigment,
      causing rapid thermal expansion that fragments pigment-containing cells and
      causes the pigment to become extracellular. This extracellular pigment is then
      recognized by the immune system as foreign.

PMID- 7728478
TI  - Vitiligo: repigmentation with dermabrasion and thin split-thickness skin graft.
AB  - BACKGROUND: Vitiligo is a common benign condition of great concern. Though a
      large number of medical and surgical treatment methods are available, none of
      them is fully dependable in all the areas. OBJECTIVE: Split-thickness skin
      grafting (STSG) has been used for the treatment of vitiligo for over three
      decades, but it did not gain popularity. This presentation evaluates the degree
      of repigmentation achieved with this technique, its complications, and drawbacks.
      METHODS: A case series of 21 patients with 32 localized, stable, and refractory
      vitiligo patches treated institutionally by dermabrasion and thin STSG has been
      presented. The patients have been followed up for 1-6 years. Three patients lost
      to follow-up before 1 year have not been included. RESULTS: The graft take was
      100% in 27 patches and 90-95% in the remaining five. One hundred percent
      repigmentation was achieved in 22 patches and 90-95% in 10. Time taken for
      satisfactory color match was 4-9 months (average, 6.3 months). The complications
      encountered were all minor and did not affect the results. CONCLUSION: This is a
      simple, outpatient procedure performed under local anesthesia resulting in an
      excellent color match on a long-term follow-up. This technique can be used over
      any part of the body, including the hair-bearing areas, without compromising the
      end results.

PMID- 7728479
TI  - An estimate of the incidence of malignant melanoma in the United States. Based on
      a survey of members of the American Academy of Dermatology.
AB  - BACKGROUND: The incidence of malignant melanoma (MM) in the United States (US)
      must be known to accurately evaluate the costs that MM imposes on the health care
      system and society in general. Furthermore, knowledge of the incidence is needed
      to determine the benefit of MM prevention programs. OBJECTIVE: To obtain an
      estimate of the incidence of MM in the US. METHODS: The data for this study were
      collected by means of a questionnaire that was sent to all members of the
      American Academy of Dermatology practicing in the US (N = 7412). RESULTS: Based
      on the mean number of MMs seen annually per dermatologist in each state and the
      number of dermatologists per state, the number of new in situ and invasive MMs in
      the US in 1992 was calculated to be 80,000. This translates to an incidence of 32
      MMs per 100,000 persons. CONCLUSIONS: Our estimate of 80,000 new MMs diagnosed in
      1992 in the US suggests that MM places much greater burdens on the US health care
      system and society than that based on current published estimates.

PMID- 7728480
TI  - Micrografting in extensive quantities. The ideal hair restoration procedure.
AB  - BACKGROUND: Smaller hair transplant grafts in greater quantities are becoming an
      unmistakable trend. As hair grow in groups of one to four, the process is
      mathematically and aesthetically logical. OBJECTIVE: To produce a natural
      appearing distribution of hair in the balding individual in an acceptable time
      frame. METHODS: Grafts reflecting natural patterns are used. Four hundred one
      hair grafts are densely packed into a frontal hairline 4-5 mm wide to create a
      transition zone between the forehead and a new hairline. Two- to four-hair grafts
      are densely packed behind the frontal zone in a graded fashion. Grafts containing
      no more than four hairs are used. RESULTS: The results produce a slightly less
      dense but better balance that looks like the natural veneer of a normal mature
      male. In women or men with thinning hair, surgically increasing density satisfies
      many patient objectives. CONCLUSION: Transplantation with one- to four-hair
      grafts in extensive quantities produces a natural "hairy" appearance without the
      artificial look typical of the large traditional grafts. By using this technique,
      many patients can be completed in just one session.

PMID- 7728481
TI  - Regrowth of grafted human scalp hair after removal of the bulb.
AB  - BACKGROUND: The bulbar region of the hair follicle contains the dermal papilla,
      hair germinative epithelial component, and active melanocytes. Thus, it has been
      assumed that the bulbar region plays a central role in hair growth,
      differentiation, and pigmentation. OBJECTIVE: To assess the regenerative capacity
      of human hair. METHODS: Individual anagen hair follicles were isolated from the
      occipital scalp and grafted onto the leg after removal of the bulb. RESULTS: The
      grafts of follicles from which the bulb and complete papilla have been excised
      regenerated new papillae and grew new pigmented hairs. CONCLUSION: The middle
      portion of the outer root sheath and dermal sheath may also contain epithelial,
      mesenchymal, and melanocyte reservoirs.

PMID- 7728482
TI  - Ambulatory phlebectomy using the tumescent technique for local anesthesia.
AB  - BACKGROUND: Ambulatory phlebectomy is a cosmetically elegant procedure that
      provides outpatient office-based surgical removal of large truncal varicose
      veins. The process of local anesthetic infiltration using traditional means is a
      time-consuming process that can be painful, and carries with it the inherent risk
      of accidental intravascular injection. OBJECTIVE: To introduce the tumescent
      technique for local anesthesia as it relates to the procedure of ambulatory
      phlebectomy and discuss the benefits of this form of anesthesia. METHODS: A
      description of the technique utilizing a dilute anesthetic solution, an injection
      syringe, and blunt-tipped anesthetic probe is provided. RESULTS: Using the
      tumescent technique for local anesthesia, large areas can be anesthetized
      quickly, safely, effectively, and relatively painlessly, offering multiple
      advantages over simple local infiltration, and eliminating the need for regional
      or general anesthesia. CONCLUSION: The authors consider the tumescent anesthesia
      technique to be highly effective and an important adjunct to the procedure of
      ambulatory phlebectomy.

PMID- 7728483
TI  - Symptomatology of vein disease.
AB  - BACKGROUND: Past studies have shown that dilated leg veins are symptomatic. It is
      not known, however, whether there are symptoms that are specific for vein disease
      and whether vein size alone predicts the presence of symptoms. OBJECTIVE: This
      study retrospectively compares groups matched by age and gender to determine to
      what degree vein disease is symptomatic, which symptoms have specificity for vein
      disease, and whether vein size alone predicts the presence of symptoms. RESULTS:
      Subjects with vein disease were found to be very symptomatic compared with
      controls. Specific symptoms were found to correlate with the presence of both
      small vein and large vein disease. Vein size alone did not predict the presence
      of symptoms. CONCLUSION: In evaluating the patient with leg symptoms the presence
      of specific symptoms increases the likelihood that vein disease is responsible
      independent of the size of the veins.

PMID- 7728484
TI  - Duplex ultrasound scanning for diagnosing lower limb deep vein thrombosis.
AB  - BACKGROUND: Traditionally, venography is used to investigate deep vein thrombosis
      (DVT), though duplex ultrasound offers a challenging, noninvasive alternative
      method and previous reports have described the use of duplex ultrasound for
      detecting proximal lesions. OBJECTIVE: To compare duplex ultrasound imaging with
      venography for both proximal and distal lesions using the probe compression
      technique and a different protocol. METHODS: Duplex scans were done by the same
      operator prior and blind to venography, which was performed using a standard
      protocol with the films being reviewed blindly by a second radiologist at a later
      date. RESULTS: In 74 patients, 21 of 22 above-knee lesions present on venography
      were detected by duplex scanning and there was complete agreement in the 52 of 52
      venogram negatives. For lesions below the knee, duplex detected 26 of 27 lesions
      also present on venography and agreed on 37 of 43 venogram negatives. These
      figures give duplex ultrasound overall accuracies of 99% and 90% (Kappa 98% and
      89%) for above- and below-knee lesions, respectively. CONCLUSION: These figures
      suggest duplex ultrasound technique compares favorably with venography for
      diagnosing both proximal and distal lesions.

PMID- 7728485
TI  - The effect of sclerotherapy on restless legs syndrome.
AB  - BACKGROUND: Restless Legs syndrome (RLS) is a disorder of unknown etiology
      characterized by relentless leg discomfort when stationary, which compels
      voluntary leg movement to obtain temporary relief. We have received anecdotal
      reports of coincidental relief from symptoms of RLS in patients following
      sclerotherapy for varicose vein disease. OBJECTIVE: To prospectively evaluate the
      concomitant occurrence of RLS and varicose veins in a population seeking
      treatment for varicose veins, and to assess the therapeutic response of RLS to
      sclerotherapy. METHODS: One thousand three hundred and ninety-seven patients were
      screened for RLS symptoms by questionnaire and interview, and for saphenous vein
      disease by clinical examination, including continuous-wave Doppler. Sclerotherapy
      with sodium tetradecyl sulphate was performed on 113 RLS patients. RESULTS: RLS
      symptoms were present in 22% (312/1,397), with a Doppler-negative to Doppler
      positive ratio of 3:2. One hundred and eleven of the 113 treated patients (98%)
      reported initial relief from RLS symptoms. Follow-up thus far shows a recurrence
      rate of 8% and 28% at 1 and 2 years, respectively. CONCLUSIONS: RLS is common in
      patients with both saphenous and nontruncal varicose vein disease, and can
      respond frequently and rapidly to sclerotherapy. This subpopulation of RLS
      sufferers should be considered for phlebological evaluation and possible
      treatment before being consigned to chronic drug therapy.

PMID- 7728486
TI  - The Australian polidocanol (aethoxysklerol) study. Results at 2 years.
AB  - BACKGROUND: An ongoing study of the safety and effectiveness of polidocanol by 98
      investigators in Australia infecting 16,804 limbs over 2 years. OBJECTIVE: To
      evaluate the complications of polidocanol and compare its effectiveness and
      complications with sodium tetradecyl sulphate (STD) and hypertonic saline.
      METHODS: A single-arm prospective study of polidocanol complications and its
      effectiveness as a sclerosant was performed. This was compared with each
      investigator's previous experience with other sclerosing agents. Patients had
      either varicose veins or venule ectasias and/or spider veins (telangiectasia). A
      total of 16,804 limbs were injected by 98 investigators. Sclerotherapy was
      performed with 0.5% or 1% polidocanol for telangiectasias or spider veins, and
      with 3% polidocanol for varicose veins. The effectiveness of the sclerotherapy
      and any complications were reported during a 2-year period. RESULTS: There were
      very few complications reported with polidocanol. There were no reported deaths
      or anaphylaxis. The investigators with previous experience of other sclerosants
      considered that the effectiveness of polidocanol was superior to STD (85%) and
      hypertonic saline (84%). Ninety percent of investigators considered that
      polidocanol had less frequent complications than STD, and 80% considered that
      these were less severe. Seventy-four percent considered that polidocanol had
      fewer side effects than hypertonic saline, and 74% considered that these were
      less severe. CONCLUSIONS: Polidocanol is an effective sclerosant that has few
      complications.

PMID- 7728487
TI  - Cutaneous cartilaginous tumor.
AB  - BACKGROUND: Only seven cases of cartilaginous tumors of the skin have been
      described in the dermatologic literature. OBJECTIVE: We studied the nature of
      cutaneous cartilaginous tumors and their clinical spectrum. METHODS: We describe
      a 56-year-old woman with a superficial cartilaginous tumor of the sole of the
      foot. The tumor appeared to be a cutaneous mass and was resected. RESULTS:
      Histologically, the tumor extended from the dermis to the subcutaneous tissue.
      Despite the presence of foci of nuclear changes that suggested a malignancy,
      there has been no recurrence in the 3 years since its removal. Our review of
      previous reports indicated that this case may have been a soft tissue chondroma.
      And it confirmed that cutaneous cartilaginous tumors comprise a superficial soft
      tissue chondroma and a true cutaneous chondroma primarily located in the dermis.
      CONCLUSION: Our case appeared to be a cutaneous cartilaginous tumor. A complete
      local removal is the treatment of choice.

PMID- 7728488
TI  - Successful cryotherapic treatment and overview of multiple clear cell acanthomas.
AB  - BACKGROUND: Clear cell acanthoma (CCA) is a usually solitary benign epidermal
      tumor. Multiple lesions are infrequently reported. OBJECTIVE: A case of multiple
      eruptive CCA is reported in which a successful cryotherapic treatment was
      performed. METHODS: A 59-year-old man with varicose veins and dry skin presented
      with 17 eruptive asymptomatic papulo-nodular lesions on both legs. RESULTS: Two
      lesions were excised with a histologically confirmed diagnosis of CCA. Other
      lesions were treated with liquid nitrogen. All the lesions resolved with minimal
      residual scarring after three to four treatments. CONCLUSIONS: Multiple CCA is a
      rare condition; fewer than 20 cases having been described. The presence of
      associated conditions like dry skin and varicose veins are discussed. Because of
      the tendency of persistence of the lesions, cryotherapic treatment may be a
      useful method of therapy.

PMID- 7728489
TI  - The razor blade biopsy technique. Introduction of the adaptor-designed shave
      biopsy instrument.
AB  - BACKGROUND: Several years ago, the razor blade was introduced as an alternative
      device for performing the shave removal and/or biopsy of skin lesions. Though
      inexpensive and readily available, the razor blade is somewhat cumbersome to use
      and poses a risk for accidental injury to the practitioner. OBJECTIVE: We
      describe a modification of the razor blade shave biopsy procedure utilizing an
      innovative adaptor design. METHODS: A comparison of the adaptor-designed shave
      biopsy instrument to the standard razor blade device is made. RESULTS: The
      modifications implemented in the adaptor design serve to enhance the comfort of
      performing biopsies, minimize accidental injury, help save time, and provide for
      a more professional appearing way in which to obtain skin specimens. CONCLUSION:
      The new adaptor design helps to facilitate the safe and effective use of the
      razor blade in dermatologic practice.

PMID- 7728490
TI  - Tissue atrophy caused by intermittent mechanical pressure on the legs
      (subcutaneous sartorial tissue atrophy)

PMID- 7728491
TI  - Sequential injection of 3% sodium tetradecyl sulphate and 20% sodium chloride in
      the treatment of refractory varicosity of the greater saphenous vein.

PMID- 7728492
TI  - Granuloma telangiectaticum after argon laser therapy of a spider nevus.

PMID- 7728493
TI  - Harvesting split-thickness grafts in direct continuity with "op-site" membrane
      biologic dressings.

PMID- 7728494
TI  - [Local Therapy of acute laryngitis. Local and systemic antibiotic therapy of
      acute respiratory tract infections. Munich, 10 October 1992].

PMID- 7728495
TI  - [Nilvadipine in the hypertensive elderly. Risk factor for cerebral insufficiency.
      Study report].

PMID- 7728496
TI  - [The heart of the matter in cardiovascular therapy. ACE-inhibition with
      Quinapril: hypertension, myocardial infarction, cardiac insufficiency].

PMID- 7728497
TI  - Formation of a primitive nervous system: nerve cell differentiation in the polyp
      hydra.
AB  - Nerve cell differentiation in the polyp Hydra is strikingly patterned: head and
      basal disk contain high densities of nerve cells. The pattern is formed by
      migration of interstitial cell precursors from the gastric region to sites of
      nerve cell differentiation in the head and basal disk. Migration occurs early in
      the final cell cycle of precursors and appears to be coincident with commitment
      to nerve cell differentiation. Following migration, each precursor divides and
      gives rise to a pair of nerve cells. Treatment of whole hydra with a neuropeptide
      stimulates formation of nerve cell precursors; differentiation of these
      precursors is regulated by a second signal, which is provided in vivo by budding
      or in vitro by injuring tissue.

PMID- 7728498
TI  - Cell fate choice during early neurogenesis in Drosophila melanogaster.
AB  - In the neuroectoderm of the Drosophila embryo, cells have to choose between the
      neural and epidermal cell fates. The decision in favor of one or the other is
      under the control of the neurogenic and the proneural genes. Their gene products
      form a signal relay that ultimately leads to the commitment of each cell to a
      given fate. Data derived from various experimental approaches suggest that the
      proteins encoded by the genes Delta and Notch act act at the membrane as signal
      and receptor, respectively, whereas the genes of the Enhancer of split and the
      achaete-scute complexes code for transcription factors, which serve to specify
      the appropriate response by regulating the activities of other genes.

PMID- 7728499
TI  - Neurogenesis in the olfactory epithelium.
AB  - The initial step in the recognition of odors occurs when individual odorant
      molecules enter the nasal cavity and interact with the sensory endings of neurons
      located in the olfactory epithelium. These neurons are unique in several
      respects. First, they are directly accessible to the external environment.
      Second, perhaps because of their exposure to toxic substances in the environment,
      they degenerate and are replenished continuously from a population of stem cells
      at the base of the epithelium. Third, the sensory neurons born in the olfactory
      epithelium of adults retain the ability to differentiate and establish synaptic
      contact with target cells in the mature olfactory bulb. These unique features,
      which are conserved phylogenetically (for example, see Blaustein et al), provide
      substantial rationale for studying neuronal genesis and differentiation in the
      olfactory epithelium. We will summarize much of what is currently known about the
      development of the olfactory epithelium, the birth and differentiation of
      olfactory receptor neurons, and the molecular correlates of these events.

PMID- 7728500
TI  - Influence of the olfactory organ on brain development.
AB  - The olfactory epithelium is a unique sensory structure that has the intrinsic
      ability to renew its receptor neurons naturally throughout the vertebrate
      lifetime. The olfactory epithelium is also a neurogenetic matrix that generates
      various cell populations during embryonic development and adulthood. Some of
      these cell types migrate to the forebrain and therefore contribute to brain
      formation. The molecules involved in cell migration and continuous reconnection
      of olfactory receptor neurons to the bulb are discussed. Experiments involving
      removal or transplants of the olfactory placode in amphibians suggest that the
      olfactory organ influences the development of the telencephalon. We believe that
      the olfactory organ has a morphogenetic influence and even possibly an inducing
      effect on the forebrain. This effect could be mediated by a number of organizing
      factors that we discuss. The profound influence of the olfactory organ on brain
      development underlines the importance of the olfactory organ for survival.

PMID- 7728501
TI  - Neurogenesis in the vertebrate retina.
AB  - Many studies concerned with the control of neurogenesis in the retina, as well as
      other parts of the nervous system, impose the dichotomy of lineage restrictions
      versus environmental regulation on the design and interpretation of experiments.
      Recent work on retinal development has focused primarily on "environmental
      regulation," and this article will review some observations from these studies
      that provide clues about signals and mechanisms that control proliferation and
      cell type determination in the retina. Although still at an early stage, these
      studies already indicate that regulatory signals are not easily categorized as
      affecting only proliferation or differentiation, but are instead pleiotropic.
      Interpretation of these findings will be considered in terms of recent work in
      other systems, which further demonstrates that signals and regulatory mechanisms
      cannot be classified so simplistically and which suggests that polarizing
      regulatory mechanisms in terms of lineage restrictions and environmental
      regulation underestimates the interplay between these types of mechanisms.

PMID- 7728502
TI  - Intrinsic and extrinsic signals in the developing vertebrate and fly eyes:
      viewing vertebrate and invertebrate eyes in the same light.
AB  - The development of complex tissues, such as the nervous system, requires
      coordinated interactions between cells, and defining the molecular basis of these
      interactions is a primary goal of developmental neurobiology. Classic
      experimental embryological studies of the developmental potential of embryonic
      neural tissues have more recently been augmented by genetic and molecular
      approaches to yield a picture of the mechanisms by which such complex neural
      structures arise during development. Perhaps coincidentally, two of the most well
      studied structures in this regard have been the eyes of Drosophila and
      vertebrates. In the past few years, a number of laboratories have focused on the
      development of the eye, of both Drosophila and vertebrates in order to understand
      the role of cell-cell interactions in the generation of organized neural
      structures. Recent evidence from both the vertebrate and Drosophila models
      suggests that common mechanisms apply in both systems, particularly in the role
      of tyrosine kinases in regulating phenotypic choices during histogenesis. Thus,
      although the eyes of flies and vertebrates have very different appearances, we
      examine the possibility that similar developmental processes are used to produce
      tissues with analogous functions.

PMID- 7728503
TI  - MASH-1: a marker and a mutation for mammalian neural crest development.
AB  - The ability to generate mice containing null mutations in any cloned gene
      promises new insights into the molecular control of mammalian neural crest
      development. This approach has recently been applied to MASH-1, a transcription
      factor in the bHLH family that is a mammalian homologue of the Drosophila
      proneural genes achaete-scute. In wild-type embryos, this gene is expressed early
      in the development of the autonomic nervous system, in apparent precursors of
      sympathetic, parasympathetic, and enteric neurons (as well as in restricted
      regions of the central nervous system). A null mutation in the MASH-1 gene
      eliminates sympathetic and parasympathetic neurons and enteric neurons of the
      foregut (esophagus); however, enteric neurons of the stomach and hindgut are only
      partially affected. Analysis with other markers indicates that the mutation acts
      after neural crest cells have localized in the anlagen of the autonomic nervous
      system to prevent neuronal differentiation. The differentiation of autonomic glia
      appears unaffected. Thus, MASH-1 provides one of the most specific mutations
      affecting neural development in mammals, as well as a valuable marker to study
      the early segregation of neural crest cell lineages.

PMID- 7728504
TI  - Neuronal intestinal dysplasia.
AB  - Neuronal intestinal dysplasia (NID) is one of the disorders of gastrointestinal
      motility with defined pathological changes. Although first described more than 20
      years ago, the disease remains controversial. The histological findings do not
      correlate with the degree of symptoms. The etiology of NID is obscure, but an
      immunologic process has been suggested. The diagnosis can be made on biopsy
      specimens performed to identify Hirschsprung's disease, but treatment must be
      individualized. The clinical course is variable, with spontaneous improvement in
      some, relentless constipation or severe dysmotility, unresponsiveness to all
      therapy, in others. Duhamel or Soave pull-through procedures can be effective in
      selected cases.

PMID- 7728505
TI  - Functional constipation.
AB  - Constipation is a common problem in children. Most patients have functional
      constipation, with or without soiling. The treatment program for functional
      constipation includes various forms of behavioral therapy and psychological
      approaches, and consists of education, disimpaction, prevention of reaccumulation
      of stools with fiber and laxatives, and reconditioning to normal bowel habits
      with frequent toileting. Most patients experience dramatic improvement in
      constipation and soiling. Complete recovery, defined as three or more bowel
      movements per week with no soiling while off laxatives, is seen less frequently,
      and often requires years of treatment.

PMID- 7728506
TI  - Methods of assessing motility of the digestive system in children.
AB  - The study of gastrointestinal motility in children has evolved during the past 25
      years. Miniaturization of tools for collecting data has created opportunities to
      study the maturation of gastrointestinal motility patterns in infants and
      complaints of abdominal pain, nausea, diarrhea, constipation and distention in
      children. Available methods, indications for testing, and data evaluation of
      pediatric esophageal, gastrointestinal, and colonic motility and manometric tests
      are discussed.

PMID- 7728507
TI  - Anorectal malformations.
AB  - The posterior sagittal approach was used to treat 792 patients with anorectal
      malformations. From these, 387 cases were evaluated 6 months to 13 years later.
      Voluntary bowel movements were present in 74.3% of the entire series. When
      distributed by diagnosis, the percentages varied: 100% in patients with rectal
      atresia and perineal fistula; 93.2% in those with vestibular fistula; 80.9% in
      those with bulbar fistula; 71.1% in those with cloacas; 66.7% in those with
      prostatic fistula, and 15.8% in those with bladder-neck fistula. Soiling was
      present in 57% of all cases. Patients with voluntary bowel movements and no
      soiling were classified as totally continent; 40.8% of the series belong to this
      group. Distributed by diagnosis, it varied from 100% in cases with rectal atresia
      or perineal fistula, 65.9% in those with vestibular fistula, 34% in those with
      bulbar fistula, 31.6% in those with cloacas, 26.3% in those with prostatic
      fistula; none of the patients with vaginal fistula or bladder-neck fistula was
      totally continent. Constipation was detected in 43.1% of all patients, and was
      more frequent in those with simple defects. Urinary incontinence was found in 19%
      of patients with cloacas who had a common channel shorter than 3 cm, and in 68.8%
      of the patients who had longer common channels. Other patients suffered from
      urinary incontinence only when they had an absent sacrum or other severe bladder
      or urethral congenital defects. An accurate diagnosis and evaluation of the
      sacrum allows us to establish, with reasonable accuracy, functional prognosis in
      most children. Those with functional disorders must be treated properly
      medically, to improve their quality of life.

PMID- 7728508
TI  - Biofeedback therapy for anorectal disorders in children.
AB  - The physiological rationale, methodology, and results of biofeedback therapy in
      the management of anorectal disorders in children are presented. Balloon
      manometry and surface electromyography (EMG) are current biofeedback methods used
      to teach improved recognition of rectal distension and coordination of muscle
      function to either maintain fecal continence or to allow proper defecation. These
      techniques have permitted a success rate of over 70% in the management of
      children with functional or organic anorectal disease refractory to conventional
      medical and behavioral therapy. Biofeedback therapy is recommended to assist in
      the successful rehabilitation of these patients.

PMID- 7728509
TI  - Autologous gastrointestinal reconstruction.
AB  - The patient with short bowel syndrome is essentially unable to absorb sufficient
      nutrients. This is caused by either short mucosal contact time, insufficient
      mucosal surface area (enterocyte mass), or a combination of the two. Management
      consists primarily in sustaining health and growth by intravenous nutrition and
      in enhancing the natural intestinal adaptation response. Surgery in the form of
      autologous gastrointestinal reconstruction (AGIR) is designed to redistribute the
      patient's own residual absorptive bowel to enhance adaptation and, possibly, to
      increase the absorptive mucosal surface by neomucosal growth. The alternative and
      ultimate fallback procedure in the management of intestinal failure is bowel
      transplantation, with its associated serious immunosuppression-related
      complications. Imaginative AGIR techniques provide new hope for the future.

PMID- 7728510
TI  - Short bowel syndrome.
AB  - Improvements in parenteral nutrition and supportive therapy have led to a growing
      population of patients who survive for prolonged periods with short bowel
      syndrome. Definitive treatment for these patients requires innovative therapy
      based on a sound knowledge of small intestinal physiology and adaptation. Current
      understanding of short bowel pathophysiology and of intestinal adaptation are
      reviewed. Medical and surgical therapeutic options are described, highlighting
      the promotion of small bowel adaptation and methods to increase the small
      intestinal mucosal mass.

PMID- 7728511
TI  - Intestinal peptides and their relevance in pediatric disease.
AB  - Gastrointestinal (GI) endocrinology has undergone rapid change during recent
      years. A greater appreciation has been gained for the role of gut peptides in the
      regulation of GI motility, secretion, blood flow, absorption, and immunity.
      Furthermore, it is increasingly recognized that these peptides function in both
      the brain and the gut as neurotransmitters. Many effects initially attributed to
      hormonal influences are now known to be neurocrine in origin. GI peptides can be
      classified into families based on their structural homology. In this article, the
      physiology of the major gut peptides is reviewed, and their role in the
      pathophysiology of GI disorders is highlighted.

PMID- 7728512
TI  - The use of Japanese and bobwhite quail as indicator species in avian toxicity
      test. ECPA/GIFAP Environmental Round Table.
AB  - A comparative analysis was made between the toxicity of plant protection products
      to two species of quail used in regulatory testing. It was shown that in general
      differences in the sensitivity between bobwhite quail and Japanese quail were
      small, and not statistically significant. It was therefore concluded that both
      species should be seen as equally suitable models for avian safety assessment.
      The mutual acceptance of studies carried out on either of these species for US
      and EC registration procedures, would lead to a reduction in vertebrate sacrifice
      and resource spending.

PMID- 7728513
TI  - An automated head space analysis method for xylenes and ethylbenzene in blood and
      water.
AB  - A sensitive, reliable method of analysis was established for water and blood
      samples containing xylene isomers (m-,o- & p-) and ethylbenzene by means of an
      automated head space sampler connected to a GC equipped with a flame ionization
      detector. Minimum detection limits (MDLs) were ca. 1 and 6 ng/mL, respectively,
      for each of the four target compounds in water and blood samples. Practical
      quantitation limits (PQLs) with precision values better than +/- 4% for duplicate
      samples were 40 and 240 ng/mL, respectively, for the individual organic compounds
      in water and blood. The analytical precision was < +/- 4% for concentrations
      above the PQL and up to 50 micrograms/mL. Calibration curves for the C2-benzene
      isomers in water and blood samples were linear (r2 > 0.9999) for individual
      analyte concentration up to ca. 50 micrograms/mL. Blank values were below the
      MDLs. The effect of cocontaminants on head space analyte concentration was
      insignificant for the anticipated range of sample composition.

PMID- 7728514
TI  - Automatic access of lexical information in Broca's aphasics: against the
      automaticity hypothesis.
AB  - A number of recent articles have claimed that the language comprehension
      impairments of so-called agrammatic patients can be characterized as being due to
      problems with the automatic access of semantic and/or syntactic information from
      the lexicon. We describe three experiments, all using tasks which probe the
      immediate and automatic access of lexical information and compare the performance
      of agrammatic patients with that of an anomic and a fluent patient. We find no
      evidence in support of the automaticity hypothesis as an explanatory account of
      the language deficits of agrammatic aphasics. Further, we argue that current
      research does not lend itself to a single-explanation account of agrammatic
      comprehension problems, and that in-depth analyses of individual patients are
      more likely to be fruitful in terms of understanding the nature of comprehension
      deficits.

PMID- 7728515
TI  - The regression hypothesis: communicative continuum vs. parametrically defined
      grammars.
AB  - Proposals concerning the regression hypothesis in aphasia presented in Grodzinsky
      (1990) and Schnitzer (1989, 1990) are compared. It is argued that Grodzinsky's
      model, which is syndrome-based, is observationally inadequate, and thus fails to
      lend aphasiological support to a neurophysiologically realized central language
      system along the lines of Chomsky's Theory of Principles and Parameters.
      Schnitzer's approach rejects the notion of mental grammars and interprets aphasic
      regression microgenetically, along the lines of Givon's continuum. It is argued
      that this approach has the potential to become truly explanatory.

PMID- 7728516
TI  - On the nature of the phonological output planning processes involved in verbal
      rehearsal: evidence from aphasia.
AB  - This paper describes the performance of an aphasic patient, R.W., in producing
      the sounds of words and in verbal rehearsal. R.W. showed evidence of retained
      abilities to access aspects of the forms of spoken words but made numerous
      phonemic paraphasias in single word production tasks. He did not show features of
      dysarthria or apraxia of speech. This pattern indicates that his deficit affected
      a process that plans the phonological forms of spoken words. R.W.'s performances
      in short-term memory and metalinguistic tasks involving single words were
      consistent with impaired rehearsal functions. The pattern of results indicates
      that rehearsal requires planning of the phonological forms of spoken items and
      suggests that activating entries in the phonological output lexicon is not
      adequate to permit rehearsal to proceed normally.

PMID- 7728517
TI  - Thematic role assignment in two severely aphasic patients: associations and
      dissociations.
AB  - Two severely aphasic patients were compared in their abilities to comprehend and
      produce locative prepositional phrases and reversible S-V-O sentences using
      English and C-VIC, a computer-based iconographic communication system. One
      patient demonstrated a significant dissociation between his performance in
      interpreting symbol order in C-VIC prepositional phrases vs. S-V-O sentences.
      Patients were able to comprehend order in C-VIC S-V-O sentences significantly
      better than they were able to assign symbol order when they produced these
      sentences. These data suggest that the procedures for assigning thematic roles to
      nouns in sentences are at least partially distinct for comprehension and
      production and that the ordering of nouns around prepositions involves conceptual
      processes distinct from those involved in ordering nouns around verbs.

PMID- 7728518
TI  - Diverging asymmetries of temporo-parietal cortical areas: a reappraisal of
      Geschwind/Galaburda theory.
AB  - The general theory on the biological foundations of cerebral dominance formulated
      in 1985 by Geschwind and Galaburda entirely relies on a postulated causal
      relationship between anatomical asymmetry of the planum temporale and functional
      lateralization of the human brain, but does not take into account asymmetry of
      another cortical region, the parietal operculum. In 40 normal volunteers whose
      handedness was specified by the Edinburgh Handedness Inventory, we assessed
      asymmetries of these two regions on MRI sagittal scans. For both measurements, a
      significantly larger leftward asymmetry was found in the 24 consistent right
      handers compared to the 16 non-right-handers. Moreover, the combination, for each
      subject, of the two indices of asymmetry, yielded four different subtypes between
      which handedness distribution significantly differed. We conclude that planum
      temporale and parietal operculum asymmetries may be divergent and that their
      convergence is strongly associated with right-handedness. Functional and
      developmental implications of these findings are discussed by reference to the
      Geschwind/Galaburda theory.

PMID- 7728519
TI  - A current-source density analysis of the long-term potentiation in the
      hippocampus.
AB  - Tetanic stimulation of presynaptic fibres induces long-term potentiation (LTP)
      which means enhancement of synaptic efficacy in the stimulated pathway for hours
      or days. In addition to that component, a permanent change occurs in the
      postsynaptic cells promoting their discharges. This latter effect called 'EPSP-to
      spike (E-S) potentiation' is thought to be mediated by voltage-sensitive channels
      in the dendrites. Current-source density (CSD) analysis was made in the CA1 area
      of hippocampal slice preparations to find if LTP causes changes of the
      transmembrane currents in the stratum radiatum which can be detected with this
      technique. Some increase of currents associated with synaptic transmission itself
      at distant dendritic areas was accompanied by a disproportional enhancement of
      other currents attributed to activation of dendritic membranes at approximately
      150 microns away from the pyramidal layer. When this current grew sufficiently
      large, it propagated towards the cell body layer. In slices where LTP had less E
      S potentiation component, the increase in CSD at distant and more proximal
      portions of the dendrites remained proportional. Paired pulse facilitation
      induced in the same slices did not produce disproportional enhancement of
      proximal dendritic currents either. Our findings support the assumptions that
      during LTP associated with E-S potentiation the probability of activation of
      voltage-sensitive channel is enhanced on the dendrites of CA1 pyramidal cells.

PMID- 7728520
TI  - The dopaminergic, glutamatergic, GABAergic bases for the action of amphetamine
      and cocaine.
AB  - The present experiments were designed to evaluate pharmacologically the role of
      three neuroanatomically related systems--dopamine, glutamate and GABA--in the
      motor-stimulant response to amphetamine and cocaine. The data indicate that
      stimulant-induced stereotypy is blocked by antagonists of all three systems and
      that agonists of all three systems administered into the striatum induce
      stereotypy. Furthermore, the interaction among them occurs in the striatum; and
      the reaction sequence, as determined by the effect of the relatively selective
      antagonists on agonist-induced stereotypy, appears to be a dopaminergic
      activation of a glutamatergic system which in turn activates a GABAergic system.
      Because the GABAergic system represents the major efferents from the striatum,
      the evidence suggests that the motor-stimulatory effects of amphetamine and
      cocaine result from a disinhibition of inhibitory systems in the thalamus,
      resulting in facilitation of excitation in the cortex.

PMID- 7728521
TI  - Conserved expression of the opioid growth factor, [Met5]enkephalin, and the zeta
      (zeta) opioid receptor in vertebrate cornea.
AB  - In addition to neuromodulation, endogenous opioids serve as growth factors. The
      naturally occurring opioid peptide, [Met5]enkephalin, termed opioid growth factor
      (OGF), has been found to be a potent and tonic inhibitor of processes related to
      growth and renewal, particularly cell proliferation. OGF mediates its actions
      through the zeta (zeta) opioid receptor. In order to determine if OGF and/or the
      zeta receptor are present in human corneal epithelium, immunocytochemistry was
      utilized. Immunoreactivity with regard to OGF and to the zeta receptor could be
      detected in the cortical cytoplasm of both basal and suprabasal epithelial cells,
      but was not associated with the cell nucleus. Investigation of the ubiquity of
      OGF and zeta receptor in the vertebrate cornea showed that both elements are
      present in a wide variety of classes of the phylum Chordata, including mammalia,
      aves, reptilia, amphibia, and osteichthyes. These results suggest that an
      endogenous opioid system related to growth may have originated as early as 300
      million years ago, and that the function of this system in cellular renewal and
      homeostasis is a requirement of the vertebrate corneal epithelium.

PMID- 7728522
TI  - Calretinin-like immunoreactivity in the optic tectum of the tench (Tinca tinca
      L.).
AB  - The distribution of calretinin-like immunopositive cells and fibers in the optic
      tectum of the tench (Tinca tinca) was studied by using a polyclonal antibody and
      the avidin-biotin-peroxidase technique. A clear laminated pattern of calretinin
      like immunoreactivity was observed. The stratum periventriculare demonstrated a
      large number of strongly labeled cells whereas in the strata album centrale and
      griseum centrale, and at the boundary between the strata griseum centrale and
      fibrosum et griseum superficiale, some scarce, weakly immunostained cells were
      observed. No immunoreactive cells were seen in the strata fibrosum et griseum
      superficiale, opticum and marginale. Cells belonging to neuronal types X and XIV,
      previously characterized using Golgi impregnation, were found to be calretinin
      like immunoreactive. Most calretinin-like immunopositive fibers were found in the
      strata fibrosum et griseum superficiale and opticum with a distribution pattern
      similar to retinotectal axons in these layers. In agreement with previous
      biochemical studies, our data suggest that, by contrast to all other classes of
      vertebrates, instead of calretinin and calbindin D-28k, only one protein is
      present in teleosts. Nevertheless, the calretinin-like immunostaining pattern in
      the teleost optic tectum was more complex than that previously described for
      calbindin D-28k. When compared to the calretinin-immunostaining in the rat
      superior colliculus, it is evident the presence in both amniotes and anamniotes
      of calretinin-immunopositive retinotectal axons. However, the distribution
      patterns of intrinsic calretinin-immunoreactive cells were different.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7728523
TI  - Axonal growth within poly (2-hydroxyethyl methacrylate) sponges infiltrated with
      Schwann cells and implanted into the lesioned rat optic tract.
AB  - Porous hydrophilic sponges made from 2-hydroxyethyl methacrylate (HEMA) have a
      number of possible biomedical applications. We have investigated whether these
      poly(HEMA) hydrogels, when coated with collagen and infiltrated in vitro with
      cultured Schwann cells, can be implanted into the lesioned optic tract and act as
      prosthetic bridges to promote axonal regeneration. Nineteen rats (20-21 days old)
      were given hydrogel/Schwann cell implants. No obvious toxic effects were seen,
      either to the transplanted glia or in the adjacent host tissue. Schwann cells
      survived the implantation technique and were immunopositive for the low affinity
      nerve growth factor receptor, S100 and laminin. Immunohistochemical studies
      showed that host non-neuronal cells (astrocytes, oligodendroglia and macrophages)
      migrated into the implanted hydrogels. Astrocytes were the most frequently
      observed host cell in the polymer bridges. RT97-positive axons were seen in about
      two thirds of the implants. The axons were closely associated with transplanted
      Schwann cells and, in some cases, host glia (astrocytes). Individual axons
      regrowing within the implanted hydrogels could be traced for up to 900 microns,
      showing that there was continuity in the network of channels within the polymer
      scaffold. Axons did not appear to be myelinated by either Schwann cells or by
      migrated host oligodendroglia. In three rats, anterograde tracing with WGA/HRP
      failed to demonstrate the presence of retinal axons within the hydrogels. The
      data indicate that poly(HEMA) hydrogels containing Schwann cells have the
      potential to provide a stable three-dimensional scaffold which is capable of
      supporting axonal regeneration in the damaged CNS.

PMID- 7728524
TI  - In vitro calcium and calmodulin-dependent kinase-mediated phosphorylation of rat
      brain and spinal cord neurofilament proteins is increased by glycidamide
      administration.
AB  - This study was carried out to determine the action of glycidamide (2,3-epoxy-1
      propanamide), a neurotoxic metabolite of acrylamide, on Ca2+/calmodulin (CaM)
      dependent protein kinase phosphorylation of cytoskeletal proteins. Acrylamide has
      been shown to increase Ca2+/CaM-dependent phosphorylation of neurofilament (NF)
      triplet proteins and autophosphorylation of Ca2+/CaM-dependent protein kinase II
      (CaM kinase II; EC 2.7.1.37). A daily intraperitoneal dose of 0.7 mmol/kg b.wt.
      of glycidamide or deionized water was administered to male Sprague-Dawley rats.
      Animals were sacrificed when signs of severe neurotoxicity became apparent at 13
      16 days of treatment. Axonal floatation was used to isolate neurofilaments (NFs)
      and endogenous kinases from brains and spinal cords of treated and control
      animals. Samples isolated from brain and spinal cord of glycidamide-treated
      animals showed increased in vitro Ca2+/CaM-dependent phosphorylation of
      endogenous and exogenous NF proteins and increased autophosphorylation of CaM
      kinase II when compared with controls. CaM binding to the alpha, beta, and beta'
      subunits of CaM kinase II and antibody binding to the alpha-subunit of CaM kinase
      II in brain supernatant isolates was increased as a result of glycidamide
      treatment. These results suggest that increased Ca2+/CaM-dependent
      phosphorylation of cytoskeletal proteins may be involved in the pathogenesis of
      glycidamide-induced neurotoxicity.

PMID- 7728525
TI  - Effects of some excitatory amino acid antagonists on imipenem-induced seizures in
      DBA/2 mice.
AB  - The behavioural and convulsant effects of imipenem (Imi), a carbapenem
      derivative, were studied after intraperitoneal (i.p.) or intracerebroventricular
      (i.c.v.) administration in DBA/2 mice, a strain genetically susceptible to sound
      induced seizures. The anticonvulsant effects of some excitatory amino acid
      antagonists and muscimol (Msc), a GABAA agonist, against seizures induced by i.p.
      or i.c.v. administration of Imi were also evaluated. The present study
      demonstrated that the order of anticonvulsant activity in our epileptic model,
      after i.p. administration, was (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)
      cyclohepten-5,10-imine maleate (MK-801) > (+/-)(E)-2-amino-4-methyl-5-phosphono-3
      pentenoate ethyl ester (CGP 39551) > 3-((+/-)-2-carboxypiperazin-4-yl)propenyl-1
      phosphonic acid (CPPene) > 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic
      acid (CCP) > 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)-quinoxaline (NBQX).
      Ifenprodil, a compound acting on the polyamine site of NMDA receptor complex was
      unable to protect against seizures induced by Imi, suggesting that the poliamine
      site did not exert a principal role in the genesis of seizures induced by Imi. In
      addition, the order of anticonvulsant potency in our epileptic model, after
      i.c.v. administration, was CPPene > MK-801 > Msc > (-)-2-amino-7-phosphonic acid
      (AP7) > gamma-D-glutamylaminomethylsulphonate (gamma-D-GAMS) > NBQX > kynurenic
      acid (KYNA) > 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX). The relationship
      between the different site of action and the anticonvulsant activity of these
      derivatives was discussed. Although the main mechanism of Imi induced seizures
      cannot be easily determined, potential interactions with the receptors of the
      excitatory amino acid neurotransmitters exists. In fact, antagonists of
      excitatory amino acids are able to increase the threshold for the seizures or to
      prevent the seizures induced by Imi. In addition, Imi acts on the central nervous
      system by inhibition of GABA neurotransmission and Msc, a selective GABAA
      agonist, was able to protect against seizures induced by Imi.

PMID- 7728526
TI  - Differentiation between dysmyelination and demyelination using magnetic resonance
      diffusional anisotropy.
AB  - Using magnetic resonance (MR) diffusion-weighted method, we examined the optic
      and the trigeminal nerves of jimpy and twitcher mice, considered to be animal
      models of Pelizaeus-Merzbacher disease, hypomyelination disorder, and Krabbe
      disease, demyelination disorder, respectively. In jimpy mice, diffusional
      anisotropy of optic nerve did not show a significant difference compared to age
      matched control mice, suggesting that diffusional anisotropy does exist in
      absence of multiple layers of myelin sheath. In twitcher mice, diffusional
      anisotropy was attenuated remarkably in the optic and trigeminal nerves. Loss of
      axonal straightness on longitudinal section confirmed by electron microscopy
      appeared to be the principal explanation for it. It is further suggested that
      this MR diffusion-weighted imaging method enables us to differentiate
      hypomyelination from demyelination in vivo.

PMID- 7728527
TI  - Feeding-related immunoreactive insulin changes in the PVN-VMH revealed by
      microdialysis.
AB  - The presence of insulin in the brain and its anorectic effect when centrally
      infused are well-established today. The question of physiological and dynamic
      changes in brain insulin in relation to meals is still unanswered and addressed
      here. Immunoreactive insulin (IRI) was measured using a sensitized RIA in 30-min
      microdialysates from VMH and PVN nuclei during and after a scheduled meal in male
      Wistar rats. We indeed observed elevations in hypothalamic IRI during the first
      30 min of 1-h meals with a progressive return towards premeal levels in spite of
      a robust satiety. When the rats were accustomed to the scheduled meals, an
      anticipatory rise in IRI was found in the hypothalamus, but not in the plasma,
      during the 30 min preceding the due time of the meal whether the meal was
      presented or not. This anticipatory rise was proportional to the number of
      repeated scheduled meals. These results first suggest that hypothalamic IRI
      changes reflect in some instances those in the plasma although there are
      exceptions that cannot be accounted for by a simple plasma-brain tissue delivery.
      Besides, hypothalamic IRI can hardly be proposed as a satiety signal. The present
      data suggest a role in satiation rather than in satiety or, perhaps, in the
      inhibition of the behavioral response of feeding that can include the
      anticipatory rise.

PMID- 7728528
TI  - Age-related changes in the antioxidative potential of cerebral microvessels.
AB  - To determine if aging in rats is associated with increased susceptibility of
      cerebral microvessels to oxidative damage microvessels from the cerebrum of 4-,
      12-, 18- and 26-month-old male Fischer 344 rats were studied. The malondialdehyde
      (MDA) (micrograms/mg protein) content of cerebral microvessels from 12-month-old
      rats (0.032 +/- 0.002) was significantly higher than that in 4-month-old rats
      (0.020 +/- 0.015) P < 0.01. The difference between 26-month-old (0.025 +/- 0.002)
      and 4-month-old rats did not reach statistical significance. The antioxidative
      potential was measured in the presence of a peroxy radical generator 2,2'
      azobis(2-amidionopropane)hydrochloride (AAPH) with monitoring of the fluorescence
      of phycoerythrin at 37 degrees C. The free radical quenching activity of cerebral
      microvessels expressed as % inhibition of phycoerythrin oxidation by AAPH was
      significantly reduced in 12-month-old (33.6 +/- 4.6%) and 18-month-old rats (26.9
      +/- 1.4%) compared with 4-month-old rats (54.3 +/- 4.9%) (P < 0.01). The 26-month
      old rats (46.4 +/- 4.6%) were not significantly different from 4-month-old rats.
      It is concluded that aging is associated with increased lipid peroxidation
      byproducts in cerebral microvessels along with a transient decrease in their
      antioxidative capacity.

PMID- 7728529
TI  - The antioxidative potential of cerebral microvessels in experimental diabetes
      mellitus.
AB  - To determine if experimental diabetes is associated with decreased antioxidative
      potential along with increased peroxidation of lipids in cerebral microvessels,
      streptozotocin-induced diabetic rats were compared with control rats and to
      diabetic rats treated with insulin. Isolated cerebral microvessels from diabetic
      rats had significantly higher concentrations of malondialdehyde (MDA;
      micrograms/mg protein) (0.0283 +/- 0.0017) compared with control (0.0201 +/-
      0.0016) or insulin-treated diabetic rats (0.196 +/- 0.0022) P < 0.01. The
      antioxidative potential was measured in the presence of a peroxy radical
      generator 2,2'-azobis(2-amidinopropane) (AAPH) and hydroxyl radical generator
      CuSO4 with monitoring of the fluorescence of phycoerythrin at 37 degrees C. The
      free radical quenching activity of cerebral microvessels expressed as %
      inhibition of phycoerythrin oxidation by AAPH was significantly reduced in
      diabetic rats (38.7 +/- 4.5%) compared with control (54.3 +/- 4.9%) or insulin
      treated diabetic rats (57.6 +/- 2.9%) (P < 0.01). The % inhibition of oxidation
      by cerebral microvessels in the presence of CuSO4 was only 15.7 +/- 3.1% and did
      not differ significantly in diabetic rats (13.1 +/- 2.1%). The results indicate
      that antioxidative potential of cerebral microvessels, especially in the presence
      of peroxy radical generator, is reduced in diabetes along with increased
      accumulation of lipid peroxidation byproducts. Increased oxidative stress may be
      one of the many mechanisms underlying the diabetes-related changes in the blood
      brain barrier.

PMID- 7728530
TI  - Immunocytochemical localization of non-NMDA ionotropic excitatory amino acid
      receptor subunits in human neocortex.
AB  - The distribution of immunocytochemically localized subunits that comprise
      ionotropic non-NMDA excitatory amino acid receptors was examined in human
      frontal, parietal and temporal association neocortex. AMPA/kainate receptor
      subunits were identified using a monoclonal antibody (3A11) that recognizes an
      epitope common to GluR2 and GluR4 [GluR2(4)], as well as polyclonal antisera that
      recognize GluR2 and GluR3 (GluR2/3). Kainate receptor subunits were identified
      using a monoclonal antibody (4F5) that recognizes an epitope common to GluR5/6/7.
      For all three antibodies used, labeling was observed in a large number of neurons
      throughout the human association neocortex with the highest immunoreactivity
      present in pyramidal-like neurons, a cellular pattern largely similar to that
      observed in the monkey neocortex. These data demonstrate the cellular
      localization patterns for some non-NMDA receptor subunits in human neocortex,
      details upon which further studies on the roles of these subunits in human
      neurological diseases can be based.

PMID- 7728531
TI  - Modulation of baroreflex function by angiotensin II endogenous to the caudal
      ventrolateral medulla.
AB  - Neurons in the ventrolateral medulla (VLM) mainly determine the tonic sympathetic
      activity. The caudal VLM (CVLM) relays baroreflex signals to the rostral VLM. We
      have reported that endogenous angiotensin II (ANG II) contributes to the ongoing
      activity of the VLM neurons. In the present study, we examined if ANG II
      endogenous to the CVLM modulates the baroreflex function in anesthetized
      normotensive Sprague-Dawley rats. Changes in renal sympathetic nerve activity
      (RSNA) in response to changes in mean arterial pressure (MAP) induced by i.v.
      infusion of phenylephrine and nitroglycerin were recorded before and after
      bilateral microinjection of [Sar1, Thr8]-ANG II, an ANG II antagonist, into the
      CVLM. The ANG II antagonist injection into the CVLM significantly increased MAP
      and RSNA by 17.6 +/- 8.0 mmHg (mean +/- S.D.) and 36.3 +/- 18.1%, respectively.
      It also significantly increased the baroreflex sensitivity (BS) from -0.49 +/-
      0.38 to -0.74 +/- 0.37%/mmHg during nitroglycerin infusion. In contrast, the BS
      examined by phenylephrine infusion was not altered by the pretreatment with ANG
      II antagonist. Injection of artificial CSF affected neither the baseline values
      of MAP and RSNA nor the BS. These results suggest that ANG II endogenous to the
      CVLM exert a modulating role in baroreflex control of RSNA.

PMID- 7728532
TI  - Sigma receptor-mediated neuroprotection against glutamate toxicity in primary rat
      neuronal cultures.
AB  - The role of the putative sigma receptor in mediating neuroprotection against
      glutamate-induced neuronal injury was examined in mature cultured rat cortical
      neurons. With the exception of the selective sigma 1 ligand (+)-3-PPP, all of the
      sigma ligands tested were neuroprotective, preventing glutamate-induced
      morphological changes and increases in LDH release. Their rank order of
      neuroprotective potency (and EC50 values) was as follows: (+)-SKF 10,047 (0.81
      microM) > (+)- cyclazocine (2.3 microM) > dextromethorphan (3.1 microM) =
      haloperidol (3.7 microM) > (+)-pentazocine (8.5 microM) > DTG (42.7 microM) =
      carbetapentane (46.3 microM). When corrected for relative sigma versus PCP
      binding affinity, it appears that a positive correlation exists between
      neuroprotective potency and sigma 1 site affinity. However, there does not appear
      to be a significant correlation between neuroprotective potency and the sigma 2
      site. Critically, none of the sigma ligands were neurotoxic when tested alone at
      concentrations at least 5-30 times their respective neuroprotective EC50 values.
      Results from preliminary experiments with the selective sigma 1 ligand (+)
      pentazocine indicated that sigma-mediated neuroprotection may involve the
      buffering of glutamate-induced calcium flux. Collectively, the results of these
      in vitro experiments demonstrate that sigma ligands are neuroprotective and
      therefore deserve further exploration as potential therapeutic agents in in vivo
      models of CNS injury and neurodegenerative disorders.

PMID- 7728533
TI  - The effect of phencyclidine on the basal and high potassium evoked extracellular
      GABA levels in the striatum of freely-moving rats: an in vivo microdialysis
      study.
AB  - The effect of phencyclidine (PCP) on the gamma-aminobutyric acid-ergic
      (GABAergic) transmission in the striatum of freely-moving rats was investigated
      using an in vivo microdialysis. The high potassium (100 mM) increased the
      extracellular GABA level to 4000% of the basal level. Although the basal GABA
      level in the striatal dialysate did not show either calcium dependency or
      tetrodotoxin (TTX) sensitivity, the high potassium evoked GABA level was reduced
      by 82% under calcium-free conditions (with 12.5 mM magnesium) and by 54% in the
      presence of 10 microM TTX. The systemic administration of PCP (7.5 mg/kg) or the
      local perfusion of PCP (100 microM and 1 mM) significantly inhibited the high
      potassium evoked GABA release in the rat striatum. The local perfusion of MK-801
      (10 microM and 100 microM), a more potent and selective N-methyl-D-aspartate
      (NMDA) receptor antagonist, also inhibited the high potassium evoked striatal
      GABA release. These drugs did not show any significant effect on the basal
      extracellular GABA level. NMDA (1 mM) either partly or completely blocked the
      effect of PCP (1 mM) or MK-801 (100 microM) on the high potassium evoked striatal
      GABA release. On the other hand, nomifensine (100 microM), a dopamine uptake
      blocker, did not show any effect on the high potassium evoked GABA release. These
      results suggest that PCP inhibited the striatal GABAergic neuronal transmission
      through its antagonism of the NMDA receptor.

PMID- 7728534
TI  - Glycine receptors in the caudal pontine reticular formation: are they important
      for the inhibition of the acoustic startle response?
AB  - The present paper sought to test the hypothesis that inhibitory glycine receptors
      (GlyRs) on giant neurons of the caudal pontine reticular formation (PnC) are
      involved in the inhibition of the acoustic startle response (ASR) in rats. First
      we provided evidence for the presence of the strychnine-sensitive inhibitory GlyR
      on PnC neurons by immunocytochemical labeling using an antibody against the alpha
      1 subunit of the GlyR. We then measured the ASR as well as two ASR inhibiting
      phenomena, short-term habituation and prepulse inhibition, after microinjections
      of the glycine antagonist strychnine (0, 5 or 10 nmol) or the glycine agonist
      beta-alanine (0, 50 or 100 nmol) into the PnC. Neither strychnine nor beta
      alanine had a measurable influence on any of the parameters of the ASR
      investigated (amplitude, short-term habituation, prepulse inhibition). In
      contrast, systemic injection of strychnine (1 mg/kg) markedly increased the ASR
      amplitude. The systemic administration of strychnine did not impair prepulse
      inhibition. The human 'startle disease' (hyperekplexia), an exaggerated startle
      response, is caused by a defect of the alpha 1 subunit of the inhibitory GlyR,
      but it is unclear at which site in the central nervous system this defect
      ultimately leads to the symptoms of hyperekplexia. Our data indicate that a
      blockade of the inhibitory GlyRs in the PnC does not affect the ASR of rats,
      suggesting that deficient GlyRs in the PnC might not be involved in the etiology
      of the human 'startle disease'. We conclude that the inhibitory GlyRs on PnC
      neurons are not necessary for the inhibition of the ASR and believe that they are
      involved in another behavioral context.

PMID- 7728535
TI  - In vivo or in vitro administration of the nitrone spin-trapping compound, n-tert
      butyl-alpha-phenylnitrone, (PBN) reduces age-related deficits in striatal
      muscarinic receptor sensitivity.
AB  - Previous research has indicated that age-related reductions in muscarinic (m)
      (e.g. oxotremorine, Oxo) agonist enhancement of striatal K(+)-evoked dopamine
      release (K(+)-ERDA) and decreased IP3 release upon m receptor (mAChR) agonist
      stimulation are partially the result of deficits in signal transduction (ST). The
      present experiments were carried out to test the hypothesis that these age
      related ST deficits occur as a result of free radical-induced alterations in
      membranes containing receptor-G protein complexes. To test this hypothesis, the
      effects of in vivo and in vitro administration of the nitrone trapping agent, n
      tert-butyl-alpha-phenylnitrone (PBN), on the Oxo-enhancement of K(+)-ERDA were
      examined. Results showed that: both in vivo (10 mg/kg/2 x day PBN i.p./14 days)
      in vitro (incubation of striatal slices 0-100 microM PBN/30 min) applications of
      PBN were effective in ameliorating age-related deficits in Oxo-enhanced K(+)
      ERDA. The results of the in vivo administration of PBN indicate that the loss of
      mAChR sensitivity in aging may be the result of oxidative stress that can be
      restored by this nitrone trapping agent. These findings show that reductions of
      endogenous or exogenous free radicals may alter one important biomarker of aging,
      i.e. the loss of sensitivity in mAChR systems. However, these results, when
      considered along with those obtained with in vitro administration indicate that
      in addition, PBN may have acute effects (e.g. perhaps membrane structural
      alterations) which can also improve mAChR responsiveness.

PMID- 7728536
TI  - Postural and sympathetic influences on brain cooling during the ultradian wake
      sleep cycle.
AB  - The influence of posture and tonic vasoconstrictor sympathetic outflow on
      systemic (ear pinna-environment) and selective (carotid rete-venous plexus) heat
      exchange underlying brain cooling was studied in cats chronically implanted with
      EEG and EMG electrodes, and transducers that measured hypothalamic, pontine and
      ear pinna temperatures across the ultradian wake-sleep cycle in a thermoneutral
      environment. Transmural pressure on heat exchanger vasculature was varied by
      keeping the animal's head above or at heart level. The vasoconstrictor
      sympathetic outflow to heat exchanger vasculature was varied both by keeping the
      animal's abdomen cool or warm and by means of bilateral common carotid ligature.
      The results show that a rise in transmural pressure enhances selective brain
      cooling and weakens systemic brain cooling. An increase in tonic vasoconstrictor
      sympathetic outflow decreases both systemic and selective brain cooling.

PMID- 7728537
TI  - Cellular and subcellular localization of AMPA-selective glutamate receptors in
      the mammalian peripheral vestibular system.
AB  - The cellular and subcellular distribution of AMPA-selective glutamate receptors
      in the mammalian peripheral vestibular system was examined using antibodies
      against peptides corresponding to the C-terminal portions of AMPA receptor
      subunits: GluR1, GluR2/R3 and GluR4. The light and electron microscopic
      immunocytochemical studies were carried out on Vibratome sections of rat and
      guinea pig vestibular sensory epithelial and ganglia. In the epithelium, GluR1
      subunit immunoreactivity appeared as accumulations of patches outlining the baso
      lateral periphery of the type I sensory cells. The GluR1-immunoreactive
      microareas were postsynaptically distributed on the membranes of calyceal
      afferent fibers. GluR2/R3 immunoreactivity was present in the sensory cells.
      GluR4 was not detected. In the vestibular ganglion, the neurons were densely
      stained with antibodies to GluR2/R3 and GluR4. The fibroblasts and the Schwann
      cells were also intensely stained with antibodies to GluR2/R3 and GluR4. In the
      sensory cells, the AMPA receptors, GluR2/R3, may function as (1) autoreceptors
      controlling afferent neurotransmitter release or (2) 'postsynaptic' receptors
      activated by the neurotransmitter release of the afferent calyx. The detection of
      GluR1 at postsynaptic sites in the afferent fibers provides anatomical evidence
      for the role of glutamate as a neurotransmitter of sensory cells. In the ganglion
      neurons, GluR2/R3 and GluR4 may represent reserve intracytoplasmic pools of
      receptor subunits in transit to the postsynaptic sites. In the Schwann cells,
      GluR2/R3 and GluR4 may be involved in neuronal-glial signalling at the nodes of
      Ranvier.

PMID- 7728538
TI  - Effects of transient forebrain ischemia on long-term enhancement of dopamine
      release in rat striatal slices.
AB  - We studied the effects of transient forebrain ischemia in vivo on long-term
      enhancement of dopamine (DA) release from rat striatal slices. One hour after the
      high-frequency tetanic stimulation (HFTS) or L-glutamate (10(-6) M) application
      in Mg(2+)-free medium to striatal slices, the high concentration of KCl (high K+)
      evoked DA release was measured. Tetanic stimulation or L-glutamate application
      significantly potentiated the high-K(+)-evoked DA release. When striatal slices
      were prepared from rats exposed to 3 min of ischemia followed by 24-h survival,
      the enhancement of DA release by HFTS was unaffected by ischemia. In contrast,
      the enhancement of DA release by HFTS was impaired in rats exposed to 5 min or 10
      min of ischemia. In addition, high K(+)-evoked DA release per se was
      significantly impaired by 10 min of ischemia. The enhancement of DA release
      elicited by pretreatment with L-glutamate was also impaired in the rats exposed
      to 5 min of ischemia. When striatal slices were prepared from rats exposed to 5
      min of ischemia with 7-day survival, the enhancement of DA release by HFTS was
      still impaired. The present results indicate that the neuronal mechanisms of the
      enhancement of DA release may be more sensitive to impairment from short periods
      of ischemia. Furthermore, the results suggest that an impairment of long-term
      enhancement of DA release by ischemia may be related the dysfunction of motor
      performance in rats exposed to ischemia.

PMID- 7728539
TI  - The contribution of quality of life to developing therapeutic nursing in special
      hospitals.
AB  - Many changes have been made to the management of special hospitals (state
      hospitals which house patients for an indeterminate stay who are mentally ill,
      who may have committed a serious offence, and who are considered to be a danger
      to society and/or to themselves). A key objective of the authority which
      currently manages these hospitals is to ensure a good quality of life (QoL) for
      patients and staff. This paper argues first that in order to meet their
      obligation to treat detained patients, mental health nurses in special hospitals
      must aim to improve the QoL of those in their care. This viewpoint is echoed by
      Coid (1993), who considers that society has a moral responsibility, which should
      be expressed formally in legislation to ensure that detained patients have a high
      QoL. The paper then addresses the issues involved in attaining an adequate QoL
      for detained patients, examines the methodological problems in QoL research and
      its indications for nurses working in this field, and outlines appropriate
      indicators for examining QoL for patients living in special hospitals. The
      intention is to initiate debate and outline an approach for mental health nurses
      towards development of a QoL measure for use in special hospitals. This is
      considered a necessary first stage if an adequate QoL is to be attained for
      detained patients.

PMID- 7728540
TI  - Schizophrenia sufferers and their carers: a survey of understanding of the
      condition and its treatment, and of satisfaction with services.
AB  - This paper reports a simple random survey of all identifiable schizophrenia
      sufferers, not in long-term residential or hospital care in one Health Board
      area. The survey was carried out (1) to assess service users' and carers'
      understanding of the illness, and (2) to assess perceptions of services by people
      with schizophrenia and their carers. A response rate of 55.6% from a sample of
      142 was achieved; 79 service users and 22 carers were interviewed. In general
      service users reported a limited understanding of the condition of schizophrenia
      and its treatment. Many reported an understanding that was either neutral or
      negative, as assessed by the Knowledge about Schizophrenia Interview'. Carers
      generally had a more positive understanding of the condition than the user group,
      but considerable scope for improvement by educational intervention remained. It
      was found that people with schizophrenia generally perceived the service in a
      positive light, but had specific dissatisfaction with regard to medication,
      vocational training and hospitalization. Both service users and carers were
      dissatisfied with information and advice from professionals and identified these
      as areas that require improvement. On the whole carers expressed less
      satisfaction with services than did people with schizophrenia.

PMID- 7728541
TI  - Primary health care for adults with learning disabilities who live in the
      community--is a specialist nurse required?

PMID- 7728542
TI  - Data capture using hand-held computers.

PMID- 7728543
TI  - A study of on-call provision in community psychiatric nursing services in
      Scotland.

PMID- 7728544
TI  - Psychological and family-centred nursing in the local community.

PMID- 7728545
TI  - Nurse or psychotherapist? The ongoing identity crisis.

PMID- 7728546
TI  - Facing up to the challenge: a view of the capacity of services to meet the needs
      of people with challenging behaviour.
AB  - Challenging behaviour is a descriptive rather than a diagnostic term. It is
      applied to various types of behaviour shown by people with learning disabilities,
      to which caregivers react strongly. Caregivers respond in this way because these
      types of behaviour are either proscribed by law or contravene a general
      perception of what is normal behaviour. Recently, services have responded to the
      challenge presented by certain clients by seeking to relocate them in less
      institutional settings and by employing staff with the necessary skills to modify
      their behaviour. However, there is considerable disagreement about what forms of
      intervention are effective and ethically acceptable, and consequently, confidence
      in the ability of caregivers to bring about change has been reduced. More recent
      work has emphasized the importance of an organizational response to the
      challenge, focusing on the need for service managers to be more explicit about
      what staff are required to do and to provide consequences for appropriate staff
      performance. The health service reforms are considered to provide sufficient
      incentives for organizations to change.

PMID- 7728547
TI  - Up from depression: strategies used by women recovering from depression.
AB  - Depression has reached epidemic proportions among women. It is estimated that one
      out of every three women between 18 and 24 years is significantly depressed. The
      purpose of this paper is to describe treatment strategies, interventions, and
      skills used by women to recover from depression. Three distinct categories of
      effective strategies that enhanced recovery are described. These include
      cognitive strategies, active behavioral strategies, and information seeking. In
      order to deliver quality psychiatric nursing care, nurses must have knowledge of
      the strategies used by women who are recovering from depression.

PMID- 7728548
TI  - An observational study of associations between nurse behaviour and violence in
      psychiatric hospitals.
AB  - A cyclical model of violence to psychiatric nurses is proposed in this paper and
      a partial test of the model is reported. The model suggests that stress induced
      by exposure to violence leads to impaired staff performance and adoption of
      behaviours which make the re-occurrence of violence more likely. We tested the
      proposal that certain staff behaviours (e.g. expressing verbal hostility) are
      associated with an increased risk of assault by observing nurse-patient
      interaction on 12 psychiatric wards (n = 103 nurses). The verbal and physical
      interaction of (1) assaulted staff, (2) staff on violent wards, and (3) staff in
      grades which experience high levels of assault, were compared with those of
      respective low risk groups. There was some evidence of an association between
      interaction patterns and violence. We conclude this paper by discussing the
      implications of the model for psychiatric nursing practice.

PMID- 7728549
TI  - Assessment of the sexuality needs of individuals with psychiatric disability.
AB  - Individuals with psychiatric disorders are at risk of experiencing a variety of
      difficulties related to their sexuality. The objective of the study described
      here was examination of nursing staff attitudes, assessment of issues related to
      the sexuality of clients, and assessment of clients' perceptions of their own
      sexuality needs. The descriptive design included staff survey, client interviews
      and chart (in-patient record) audits. The setting was a tertiary care provincial
      psychiatric hospital in Ontario, Canada. One hundred in-patient records were
      randomly selected for a concurrent chart audit, followed by client interviews.
      Staff surveys included 68 nurses. Clients were found to be at increased risk for
      sexual aggression and sexually transmitted diseases. Clients identified learning
      needs regarding contraception and safe sexual practices. The nurses who completed
      the staff survey reported high levels of comfort related to clients' sexuality,
      yet infrequent teaching related to safe sexual practices. Individuals with
      psychiatric disorders are at increased risk for a number of problems related to
      sexuality and identify several learning needs. There is also a risk that these
      needs go unrecognized by nursing staff.

PMID- 7728550
TI  - An examination of therapeutic principles and practice in two forensic units.
AB  - The study reported here was conducted following claims made by a forensic
      psychiatric unit (called Ambrose Unit) that, in effect, it functioned as a
      therapeutic community. The study aimed to compare this claim with findings from
      the Attitude to Treatment Questionnaire (ATQ) that was administered to the staff
      of the unit. For the purposes of the exercise, the unit was matched with another
      similar unit that had not claimed to function therapeutically. It was
      hypothesized that, in keeping with their therapeutic claims, scores for staff
      from the Ambrose Unit would be more liberal than those for staff from the other
      unit (called Delphi unit). A series of ANOVA calculations supported this
      hypothesis and other hypotheses regarding political and social attitudes of staff
      working in these units. However, the discussion considers in more detail, scores
      from the ATQ, and questions these results. The nature of therapeutic community
      research in general is also considered and the validity of results generated from
      such research is discussed. Finally, the limitations imposed by the difficulty
      with which terms in this area are defined is acknowledged.

PMID- 7728551
TI  - Nursing advocacy: an ethic of practice.
AB  - Advocacy is an important concept in nursing practice; it is frequently used to
      describe the nurse-client relationship. The term advocacy, however, is subject to
      ambiguity of interpretation. Such ambiguity was evidenced recently in criticisms
      levelled at the nursing profession by hospital ethicist Ellen Bernal. She
      reproached nursing for using 'patient rights advocate' as a viable role for
      nurses. We maintain that, for nursing, patient advocacy may encompass, but is not
      limited to, patients rights advocacy. Patient advocacy is not merely the defence
      of infringements of patient rights. Advocacy for nursing stems from a philosophy
      of nursing in which nursing practice is the support of an individual to promote
      his or her own well-being, as understood by that individual. It is an ethic of
      practice.

PMID- 7728552
TI  - Out on a limb: a qualitative study of patient advocacy in institutional nursing.
AB  - This study explored the nature of patient advocacy among 40 institutionally
      employed registered nurses, nurse managers, clinical nurse specialists and
      nursing administrators. Participants were asked to define patient advocacy, to
      discuss their experiences with advocacy in institutions and their perceptions of
      risk associated with advocacy in institutional settings, and to identify one
      concept central to patient advocacy. The results delineated conceptual
      definitions of advocacy and numerous factors that influence nurses' decisions
      about acting as patient advocates in institutions. Additionally, they showed
      striking similarities between conceptual terms used to define advocacy and terms
      used to define caring.

PMID- 7728553
TI  - Patient advocacy at the end of life.
AB  - Caring for the competent, fragile, elderly patient at the end of life is becoming
      increasingly challenging. This case explores several ethical areas of concern
      that arise when caring for patients who have written durable powers of attorney
      for health care decisions and face life or death choices. Areas covered are
      informed consent with the elderly patient, the family's right to be involved in
      decision-making, futility of treatment, and the nurse's role as patient advocate
      during times of difficult decision-making. Recommendations for increased nursing
      intervention during these times are incorporated.

PMID- 7728554
TI  - Moral rights and the ethics of nursing.
AB  - This paper explores the nature of rights, and their implications for the ethics
      of nursing. A right is seen as an entitlement which is justified on moral and/or
      legal grounds, and which may take the form of a right of action or a right of
      recipience, or both; in either case, correlative duties are generally imposed on
      others. Some of the conflicts which can occur among two or more conflicting
      rights are examined through three hypothetical scenarios, and approaches to their
      resolution are suggested. The question of whether nurses, as nurses, possess
      rights is then considered, and it is suggested that they do not. In conclusion,
      it is argued that, if rights are to be a helpful concept, they must be carefully
      defined and analysed, and their relationship to one another, and to duties, must
      be clarified.

PMID- 7728555
TI  - The influence of gender, education and experience on moral sensitivity in
      psychiatric nursing: a pilot study.
AB  - The purpose of this study was to investigate some factors which may influence
      moral decision-making in psychiatric nursing practice. The Moral Sensitivity
      Questionnaire, a 30-item, seven-point Likert scale, measures six dimensions that
      are assumed to be related to moral sensitivity. In scoring, the test is divided
      into six categories: interpersonal orientation, structuring moral meaning,
      expressing benevolence, modifying autonomy, experiencing conflict, and reliance
      on medical authority. Seventy-nine nurses, employed in the same psychiatric
      district, were included in the sample. Significant differences were found for
      some items in five of the six categories regarding gender, post-basic nursing
      education, experience as a mental care worker and type of clinical setting.

PMID- 7728556
TI  - Ethical aspects of judging the alternative treatment of children with cancer.
AB  - In recent decades the improved treatment of childhood cancer has increased the
      proportion of children being cured. However, the intensive treatment required
      also implies a heavy burden for the children and their families. The purpose of
      this article is to judge the ethical aspects of different treatment regimens used
      for children with cancer by means of a case study. The analysis is based on the
      ethical model by Beauchamp and Childress. The assessment is based on every
      person, or group of persons, involved and is on the principles of autonomy,
      nonmaleficence, beneficence and justice. The analysis shows that intensification
      of treatment of children with cancer is ethically justified from a deontological
      point of view. The consequences are more difficult to anticipate from a
      utilitarian perspective.

PMID- 7728557
TI  - Mass childhood immunization: some ethical doubts for primary health care workers.
AB  - The mass childhood immunization programme has traditionally been viewed as a safe
      and effective preventative measure by health promoters, primary health care
      professionals and governments. This consensus has meant that immunization has
      rarely been viewed as ethically problematic. A number of recent changes in the
      context of the delivery of health care, particularly the emphasis on consumerism
      and the effect of the marketization of services, makes timely an examination of
      ethical, social and political issues. This article examines four main grounds for
      problematizing the mass childhood immunization programme. These are: clinical
      research evidence about the safety and efficacy of vaccines; the masking of wider
      social and political determinants of ill health; the contradictory strictures
      about collective and individual rights in relation to immunization; and the
      uniqueness of childhood immunization as a physical intrusion into a healthy body.
      The implications of these ethical issues are discussed in relation to informed
      consent and the need for a 'greenfield' review that includes the views of
      dissenting parents, lawyers and moral philosophers, as well as health
      professionals.

PMID- 7728558
TI  - Compliance or collaboration? The meaning for the patient.
AB  - Noncompliance exasperates health care professionals, leaves them worrying about
      the effective outcome of medical care, and results in noncompliant patients being
      labelled as 'difficult' or 'troublesome'. It is suggested that professionals who
      label a patient as noncompliant are following convenient paternalistic principles
      rather than considering the impact of a prescribed regimen on an individual
      patient. In this paper, the author considers autonomy and respect to be foremost
      in patient care. Further, compliance does not necessarily indicate that both
      professional and patient have developed a collaborative understanding
      relationship. Noncompliance is described as a lack of recognition by the health
      care professional of the meaning of the regimen to the patient. Treatment
      interventions will be most successful when the patient participates in the
      prescription. Without acknowledgement of the patient as an equal partner, and
      listening to his or her narrative, care will be, at best, paternalistic.

PMID- 7728559
TI  - Nursing ethics in Hungary.

PMID- 7728560
TI  - Code of ethics for nurses in Australia. The Australian Nursing Council Inc., the
      Royal College of Nursing, Australia, and the Australian Nursing Foundation.

PMID- 7728561
TI  - Vulnerability of nurses in private nursing homes.

PMID- 7728562
TI  - Intensive multimodality therapy for carcinoma of the esophagus and
      gastroesophageal junction.
AB  - BACKGROUND: We designed a trial of intensive multimodality therapy for carcinoma
      of the esophagus and gastroesophageal junction to assess tumor response and
      operability after neoadjuvant chemotherapy and to determine the impact of
      trimodality therapy on longterm survival. METHODS: Thirty-two patients with
      resectable (clinical stage IIa, n = 17; IIb, n = 1; III, n = 14) squamous cell
      cancer (n = 15) or adenocarcinoma (n = 17) were treated with neoadjuvant
      chemotherapy (cisplatin, 5-fluorouracil, leukovorin), resection, and
      postoperative chemoradiotherapy (hydroxyurea, 5-fluorouracil; 50-66 Gy). RESULTS:
      Use of neoadjuvant chemotherapy yielded the following results: a measurable
      clinical response in 22 patients, stable disease in eight patients, disease
      progression in one patient, and death in one patient. Thirty-one patients
      underwent resection, with the following results: two operative deaths (6.5%) and
      nonfatal morbidity in 17 (59%); the median hospital stay was 13 days. Pathologic
      staging was stage 0, n = 1; I, n = 2; IIa, n = 11; IIb, n = 5; III, n = 7; and
      IV, n = 5. Postoperative chemoradiotherapy was completed in 23 patients with one
      death, for an overall treatment-related mortality rate of 12.5% (four of 32). At
      a mean follow-up of 22.5 months, median survival is 19.7 months and 14 patients
      are alive and disease free. CONCLUSIONS: Neoadjuvant therapy for cancer of the
      esophagus and cardia results in good tumor response. Esophagectomy in this
      setting can be accomplished with acceptable morbidity and mortality. Results of
      an interim analysis of survival are encouraging and suggest that further
      investigation of this regimen is warranted.

PMID- 7728563
TI  - Validity of major cancer operations in elderly patients.
AB  - BACKGROUND: As the population ages, more elderly individuals will be at risk for
      the development of gastrointestinal malignancies traditionally treated with
      radical operation. In the past, many major cancer operations were reserved for
      patients < 65 or 70 years of age, but as the life expectancy for a 70-year-old
      has improved, this policy has been questioned. METHODS: We examined the records
      of 124 consecutive patients who underwent one of three major operations
      (esophagogastrectomy, major liver resection, pancreatoduodenectomy) for
      gastrointestinal cancer during the past 6 years to determine if preoperative risk
      factors, operative mortality, length of stay, length of procedure, estimated
      blood loss, rate of major complication, or Kaplan-Meier survival was different
      for patients > or = 70 years of age as compared with younger patients. RESULTS:
      For patients at our institution undergoing esophagogastrectomy, major liver
      resection, or pancreatoduodenectomy, we found no significant difference in any of
      the parameters measured. There was no significant difference in any parameter
      when comparing patients > or = 70 versus < 70 years of age. CONCLUSIONS: We
      conclude that patients > or = 70 years of age are not necessarily less suitable
      candidates for major cancer operations than are those < 70 years of age if other
      risk factors are acceptable. Elderly patients should be included in clinical
      trials.

PMID- 7728564
TI  - Breast cancer after breast augmentation with silicone implants.
AB  - BACKGROUND: Although epidemiological studies have failed to demonstrate an
      increased incidence of breast cancer in women who had undergone prior prosthetic
      augmentation mammoplasty (PAM), it has been reported that when breast cancer
      arises in this group it presents mostly in a palpable form and at a more advanced
      stage. This is thought to be secondary to suboptimal mammographic evaluation
      caused by the masking effect of the implant. This study was undertaken to
      determine, in our experience, whether breast cancer arising in women who had
      undergone PAM could be detected in a prepalpable form by mammography and whether
      it presented at a more advanced stage as compared with nonaugmented women with
      breast cancer. METHODS: The charts of 22 patients, treated by at least one of the
      authors, in whom 23 breast cancers developed after PAM (group A) were
      retrospectively reviewed. The comparison groups consisted of 611 nonaugmented
      patients who underwent 636 procedures for the treatment of primary breast cancer
      at our institution (group B) and the surveillance, epidemiology, and end results
      (SEER) data (group C). Parameters studied were mode of detection, tumor size,
      axillary lymph node involvement, and histopathology. RESULTS: No significant
      differences between the groups were found in mean tumor size (group A vs. group
      B), the incidence of preinvasive cancer (group A vs. group B) or axillary lymph
      node involvement (group A vs. group B and group A vs. group C). Breast-preserving
      surgery was performed significantly less in augmented patients (group A vs. group
      B). CONCLUSION: We conclude that prepalpable and preinvasive breast cancer can be
      detected in the PAM patient by mammography and that the stage of presentation in
      this group is not significantly different than in nonaugmented patients. Total
      mastectomy is preferred over breast-preserving procedures for the treatment of
      breast cancer in the PAM patient.

PMID- 7728565
TI  - Extremity malignant peripheral nerve sheath tumors (neurogenic sarcomas): a 10
      year experience.
AB  - BACKGROUND: Prior studies have shown a high rate of local recurrence and a dismal
      overall prognosis in malignant peripheral nerve sheath tumors (MPNSTs). METHODS:
      Thirty-three patients who had undergone primary treatment for localized extremity
      MPNSTs between 1982 and 1992 were reviewed. These cases were derived from a
      prospective database of 890 adult extremity soft-tissue sarcomas (STS). MPNSTs
      were compared with other extremity STS. RESULTS: MPNSTs were more often high
      grade and deep compared with other extremity STS (94% vs. 72% [p = 0.009] and 97%
      vs. 76% [p = 0.01], respectively). Location (upper or lower extremity), size (> 5
      cm vs. < or = 5 cm), and status of margins after surgical resection (positive or
      negative for disease) did not differ between the two groups. When deep and high
      grade MPNSTs were compared with deep and high-grade STS, a more aggressive local
      treatment was applied to MPNSTs with a higher number of amputations for MPNSTs
      (32%) compared with STS (9%; p < 0.001). In order to obtain adequate margins, 16
      of 21 MPNSTs arising from major nerves required either amputation (n = 8) or
      nerve resection (n = 8). Adjuvant radiotherapy was used in 48% of deep and high
      grade MPNSTs, and 3-year local disease-free survival was 70%. Survival of deep
      and high-grade MPNSTs was comparable with other deep and high-grade STS (3-year
      survival 50% vs. 69%, respectively; p = 0.1). CONCLUSION: MPNSTs show adverse
      clinicopathologic features compared with other STS. However, when treated
      aggressively, MPNSTs have an outcome similar to other deep and high-grade
      extremity STS.

PMID- 7728566
TI  - Elective hand surgery in the breast cancer patient with prior ipsilateral
      axillary dissection.
AB  - BACKGROUND: We wished to determine if complications after elective hand surgery
      were greater in women with previous mastectomy and axillary dissection than in
      those without. METHODS: We surveyed records of all women undergoing carpal tunnel
      release by the senior author (W.J.D.) from 1983 to 1993. The postaxillary
      dissection group (group A) was made up of 15 women; seven had some postdissection
      lymphedema. Group B was made up of 302 other patients who had not undergone
      breast surgery or axillary dissection. Anesthetic and surgical techniques were
      identical for both groups, with i.v. regional anesthesia used most commonly.
      RESULTS: No patient in the axillary dissection group developed any postoperative
      infection or had any worsening of preexisting lymphedema or onset of new arm
      swelling after ipsilateral carpal tunnel release. The nonaxillary dissection
      group had a postoperative infection rate of 3.6%; all infections were superficial
      and resolved with conservative therapy. In addition, 31 women experienced other
      complications, including 13 with hand/finger stiffness and four with reflex
      dystrophy. Fifteen required formal hand therapy. CONCLUSIONS: Women with prior
      ipsilateral axillary dissection can safely undergo elective upper extremity
      surgery, provided strict sterile technique and appropriate anesthetic and
      surgical precautions are observed. Patients having undergone previous axillary
      dissection should not be prohibited from future limb manipulations, including
      venepunctures, blood pressure measurements, or elective surgery.

PMID- 7728567
TI  - Recurrence patterns and complications in endometrial adenocarcinoma with cervical
      involvement.
AB  - BACKGROUND: Cervical involvement in endometrial carcinoma is a diverse entity,
      and the optimal management of these patients is not well understood. METHODS:
      Recurrence patterns and complications in 202 patients with histologically
      confirmed endometrial carcinoma with cervical involvement were retrospectively
      studied. RESULTS: The 5-year actuarial survival rate for all patients was 65%.
      Recurrences were documented in 80 (40%) of the patients, and the overall long
      term survival rate in this group was 4%. Patients treated with radical
      hysterectomy (n = 33) had a 6% isolated pelvic recurrence rate and the lowest
      serious complication rate among the five treatment groups despite having the
      highest frequency of risk factors for recurrence among any of the groups studied.
      Patients treated with extrafascial hysterectomy alone (n = 37) had a 14% pelvic
      recurrence rate and very few complications. When radiotherapy preceded
      extrafascial hysterectomy (n = 37), the frequency of pelvic recurrences was 30%,
      and 19% experienced serious gastrointestinal or genitourinary tract
      complications. When radiotherapy followed extrafascial hysterectomy (n = 68), the
      pelvic recurrence rate was 24%, and 13% experienced serious complications.
      Overall, 24% of patients (49 of 202) had isolated pelvic recurrences, whereas 10%
      (21 of 202) had isolated distant recurrences and 5% (10 of 202) were
      simultaneously diagnosed with both pelvic and distant recurrences. CONCLUSIONS:
      This large data base suggests that older conventional forms of therapy,
      particularly those using preoperative radiotherapy, subject the patient to
      significant morbidity over a 5- to 10-year period and, in terms of local control,
      are not necessarily superior to therapeutic modalities using primary surgical
      evaluation, such as radical hysterectomy. Consideration of primary surgery should
      be given in the appropriate situation, and radical hysterectomy should be
      considered when gross cervical involvement is encountered and intraoperative
      exploration does not show obvious extrauterine disease.

PMID- 7728568
TI  - Microvascular craniofacial reconstruction in cancer patients.
AB  - BACKGROUND: Resections of large malignancies involving the middle and upper
      thirds of the face and cranium result in complex defects, posing a difficult
      challenge for the reconstructive surgeon. Free tissue transfer may be the best
      means of reconstruction. METHODS: We reviewed 54 consecutive microvascular
      craniofacial reconstructions after tumor ablation performed at the University of
      Texas M.D. Anderson Cancer Center from May 1988 to September 1992. Information
      regarding patient characteristics, tumor stage and histology, history of prior
      therapy, the defect after tumor ablation, and the details of the reconstruction
      were entered in a microcomputer database at the time of the initial surgery. Free
      flap outcome, the number and type of complications, control of malignant disease,
      and the use of adjuvant therapy were recorded prospectively. RESULTS: Patients
      had defects of the scalp and cranium (15 of 50) or of the maxilla/orbit/cranial
      base (35 of 50) after resections for a variety of tumors. Immediate
      reconstruction was completed in 40 patients and delayed in 10. Prior therapy
      included surgery (39 of 50) and/or radiotherapy (35 of 50). The free flap success
      rate was 96% (52 of 54). In patients with successful flaps, significant wound
      complications occurred in 13.5% of patients (seven of 52) and donor site problems
      in 11.1% (six of 54) for an overall complication rate of 24.1% (13 of 54). There
      were no operative deaths or neurologic complications. The timing of surgery or a
      history of prior surgical therapy or radiotherapy did not significantly influence
      the complication rates. CONCLUSION: Free tissue transfers provide optimal
      restoration of large craniofacial defects resulting from cancer resection.

PMID- 7728569
TI  - Construction and expression in tumor cells of a recombinant vaccinia virus
      encoding human interleukin-1 beta.
AB  - BACKGROUND: Human interleukin-1 beta (hIL-1 beta) injected intratumorally has
      demonstrated growth inhibition of transplanted subcutaneous tumors in mice,
      regression of metastatic lesions, resistance to tumor rechallenge, and increased
      survival. Vaccinia virus (VV) can be genetically engineered to produce cytokines
      and may be an effective vector for gene therapy of cancer. This study was
      designed to (a) construct a VV expressing hIL-1 beta, (b) assess tumor cell
      infection in vitro with this construct, (c) measure hIL-1 beta production, and
      (d) assess the bioactivity of the secreted cytokine. METHODS: The hIL-1 beta gene
      was amplified from a plasmid clone using polymerase chain reaction (PCR) and then
      cloned into a homologous recombination (HR) and expression vector, which was used
      to insert the hIL-1 beta gene into the VV genome. Selection of the recombinant VV
      (vMJ601hIL-1 beta) was based on inactivation of viral TK and expression of beta
      galactosidase. vMJ601hIL-1 beta infectivity and cytokine production was assessed
      by infecting tumor cell lines and analyzing culture supernatants for hIL-1 beta.
      Bioactivity of the hIL-1 beta produced was demonstrated using an IL-1 dependent T
      helper cell line. RESULTS: The hIL-1 beta gene was successfully cloned into the
      VV genome by HR, which was confirmed by PCR. vMJ601hIL-1 beta efficiently
      infected tumor cells, as shown by increased hIL-1 beta secretion (0 to > 500
      ng/ml) and morphologic evidence of viral cytopathic effect. vMJ601hIL-1 beta
      infected cells secreted large amounts of hIL-1 beta (mean 772 ng/10(6) cells/24
      h). The secreted hIL-1 beta was bioactive (mean bioactivity 6.8 x 10(8) U/mg of
      hIL-1 beta). CONCLUSIONS: (a) hIL-1 beta can be cloned into VV, (b) vMJ601hIL-1
      beta retains its infectivity, (c) a large amount of hIL-1 beta is secreted, and
      (d) the secreted hIL-1 beta is bioactive. Recombinant VV may allow in situ
      cytokine gene delivery and expression in established tumors.

PMID- 7728570
TI  - Parietal pleurectomy for malignant pleural effusion.
AB  - BACKGROUND: Malignant pleural effusions are seen frequently in clinical practice
      and are most commonly caused by breast cancer and lung cancer. Standard treatment
      usually consists of complete drainage of the pleural space via a chest tube and
      instillation of a pleural irritant to obtain pleural symphysis. In a majority of
      instances, such treatment effectively controls the pleural space; however,
      standard treatment fails in some cases. METHODS: Twenty-four patients who did not
      respond to standard treatment for malignant pleural effusion were subjects for
      parietal pleurectomy, which was usually performed through an axillary
      thoracotomy. In several cases, decortication was also necessary. The study
      population was composed of 18 women and six men. Twelve of the patients had
      carcinoma of the breast, five carcinoma of the lung, and four carcinoma of the
      ovary. RESULTS: Three patients died in the perioperative period to give an
      operative mortality of 12.5%. The other 21 patients all had satisfactory control
      of their recurrent malignant effusions. Their survival time ranged from 2 to 30
      months (average 10.6). CONCLUSIONS: Parietal pleurectomy is an effective
      operation for recurrent malignant pleural effusion. However, because of its
      significant morbidity and mortality, it should be reserved for failures of
      standard treatment, and patient selection is important.

PMID- 7728571
TI  - Eleven years' experience with pericardial-peritoneal window in the management of
      malignant and benign pericardial effusions.
AB  - BACKGROUND: Before 1983 we routinely used subxiphoid drainage for the management
      of pericardial effusions. Pericardial-pleural window through a left anterior
      thoracotomy was used in selected patients. Due to frustration over the rate of
      recurrent pericardial effusions with subxiphoid drainage alone and concern over
      the higher morbidity with thoracotomy, the creation of a 3-cm pericardial
      peritoneal window in the fused portion of the pericardium and diaphragm overlying
      the left lobe of the liver was added to subxiphoid drainage in 1983. METHODS:
      This study is a retrospective chart review of the 33 patients undergoing
      pericardial-peritoneal window from 1983 through 1993. Eighteen patients had
      malignancies, mainly lung and breast, and 15 had benign pericardial effusions.
      RESULTS: The procedure was well tolerated, with a 30-day mortality of 9%;
      however, no deaths were directly related to the pericardial effusion or the
      procedure. No patient developed peritoneal carcinomatosis or diaphragmatic
      hernia. One patient developed recurrent pericardial effusion during follow-up,
      and two required pericardiectomy for constrictive disease. Among those with
      malignancies, patients with breast cancer had the longest survival after
      pericardial-peritoneal window. CONCLUSIONS: Pericardial-peritoneal window is a
      simple, safe, and effective procedure and applicable to most patients with
      malignant and noninfectious benign pericardial effusion, including those with
      tamponade.

PMID- 7728572
TI  - Stomal seeding of head and neck cancer by percutaneous endoscopic gastrostomy
      tube placement.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes have replaced
      nasogastric tubes and Stamm gastrostomy tubes as a preferred means of feeding for
      patients with head and neck cancers, as recommended by the results of large
      series. A patient with stomal seeding of squamous cell carcinoma of the upper
      aerodigestive tract by PEG placement was reported. A review of literature was
      performed. METHODS: A Medline search of implantation of squamous cell carcinoma
      from the upper aerodigestive tract to PEG exit site since the introduction of PEG
      was performed. RESULTS: Two reports of implantation of squamous cell carcinoma of
      the upper aerodigestive tract to PEG exit site were found. Both patients and our
      patient were staged T4. CONCLUSIONS: Implantation of squamous cell carcinoma from
      the upper aerodigestive tract to the PEG exit site is a rare and late
      complication. Its prevalence is not known. For patients with a significant amount
      of squamous cell carcinoma in the upper aerodigestive tract, we recommend Stamm
      gastrostomy over PEG insertion by the pull technique. There is no report of such
      late complication by the push technique.

PMID- 7728573
TI  - Venographic surveillance of tunneled venous access devices in adult oncology
      patients.
AB  - BACKGROUND: Tunneled venous access devices (VADs) are often essential in the care
      of patients with advanced malignancies, but they carry an uncertain risk of
      thrombosis. METHODS: To determine the incidence of venoocclusion related to
      silicone VADs in a population of adult oncology patients, we prospectively
      studied 50 individuals with upper extremity venograms approximately 6 weeks after
      their VADs had been implanted. Twenty-one of these patients were reevaluated with
      venograms approximately 12 weeks after catheterization. In addition, venograms
      were performed on a separate group of 24 patients who needed catheterization of
      axillary-subclavian veins that had been catheterized in the past. RESULTS: The 6
      week venograms in the prospective study showed partial venous obstruction in 15
      patients (30%), whereas three (6%) had developed symptomatic total venoocclusion
      by this time. The 12-week venograms showed two additional complete occlusions.
      Venograms of 30 previously catheterized veins showed complete venoocclusion in
      nine (30%), although only two had a history of thrombosis. CONCLUSIONS: Our
      observations indicate that VADs frequently cause partial venoocclusion within the
      first 6 weeks of catheterization and that permanent venous damage from VADs is
      common, even without a history of VAD-related thrombosis.

PMID- 7728574
TI  - Gene therapy in surgical oncology.
AB  - BACKGROUND: Surgery remains the only potentially curative treatment modality for
      the majority of patients with solid tumors. Conventional chemotherapy and
      radiotherapy only have roles as adjuvant or palliative therapies for most common
      cancers. Two decades of research have led to the first attempts at producing and
      introducing clinically useful genetically modified cells into humans. METHODS:
      Modern molecular methods have been developed that allow the stable transfer of
      foreign DNA sequences into human and other mammalian somatic cells. At the
      present time, gene therapy predominantly involves gene insertion either directly
      into a target cell in situ or into an appropriate cell in vitro that is then
      introduced to a physiologically relevant site. We present an overview of the
      potential applications of molecular biology for practicing surgeons, particularly
      in the field of surgical oncology, to show how genes are harnessed and inserted
      into target somatic cells. CONCLUSIONS: Although significant clinical therapies
      have and will continue to emerge from these initial experiments, only the future
      will provide evidence of whether the present technical skills are sufficient to
      have an impact on the long-term benefits for patients with cancer and genetic
      defects.

PMID- 7728575
TI  - Metastatic neuroblastoma--does combining several "magic bullets" make a
      difference?

PMID- 7728577
TI  - Making up the medicine: apothecaries in sixteenth- and seventeenth-century
      Edinburgh.

PMID- 7728576
TI  - Complete surgical resection combined with aggressive adjuvant chemotherapy and
      bone marrow transplantation prolongs survival in children with advanced
      neuroblastoma.
AB  - BACKGROUND: A multi-modality approach combining surgery with aggressive
      chemotherapy and radiation is used to treat advanced neuroblastoma. Despite this
      treatment, children with advanced disease have a 20% 2-year survival rate.
      Controversy has developed regarding the efficacy of combining aggressive
      chemotherapy with repeated surgical intervention aimed at providing a complete
      surgical resection (CSR) of the primary tumor and metastatic sites. Several
      prospective and retrospective studies have provided conflicting reports regarding
      the benefit of this approach on overall survival. Therefore, we evaluated the
      efficacy of CSR versus partial surgical resection (PSR) using a strategy
      combining surgery with aggressive chemotherapy, radiation, and bone marrow
      transplantation (BMT) for stage IV neuroblastoma. METHODS: A retrospective study
      was performed with review of the medical records of 52 consecutive children with
      neuroblastoma treated between 1985 and 1993. Twenty-eight of these 52 children
      presented with advanced disease, 24 of which had sufficient data to allow for
      analysis. All children were managed with protocols designed by the Children's
      Cancer Group (CCG). Statistical analysis was performed using Student's t test,
      chi 2 test, and Kaplan-Meier survival curves. RESULTS: Mean survival (35.1
      months) and progression-free survival (29.1 months) for the CSR children was
      statistically superior to that of the PSR children (20.36 and 16.5 months, p =
      0.04 and 0.04, respectively). Similar significance was demonstrated using life
      table analysis of mean and progression-free survival of these two groups (p =
      0.05 and < 0.01, respectively). One-, 2-, and 3-year survival rates for the CSR
      versus the PSR group were 100%, 80%, and 40% versus 77%, 38%, and 15%,
      respectively. An analysis of the BMT group compared with those children treated
      with aggressive conventional therapy showed improvement in mean and progression
      free survival. CONCLUSIONS: Aggressive surgical resection aimed at removing all
      gross disease is warranted for stage IV neuroblastoma. CSR is associated with
      prolonged mean and progression-free survival. BMT prolongs mean and progression
      free survival in children with stage IV disease. These results suggest that CSR
      and BMT offer increased potential for long-term remission in children with
      advanced neuroblastoma.

PMID- 7728578
TI  - Medical controversy in the nineteenth-century American South: botanics vs.
      allopaths.

PMID- 7728579
TI  - Abraham Lincoln, medical jurisprudence, and chloroform-induced insanity in an
      1857 murder trial.

PMID- 7728580
TI  - Reading literary theory, reading Ivan Ilych: old wine in new wineskins.

PMID- 7728581
TI  - Alexander L. Tchijevsky: "exquisite poet-philosopher, " "creator of new sciences,
      "or "charlatan".

PMID- 7728582
TI  - Sepsis decreases phenylephrine- and KCl-induced aortic ring contraction and
      decreases the frequency of oscillations in active wall tension.
AB  - Impaired vascular contractility is a hallmark of sepsis and endotoxemia. The
      purpose of the present investigation was to determine mechanisms responsible for
      the abnormal contractility in sepsis using the rat cecal ligation and perforation
      (CLP) model. 24 h after CLP or sham surgery, rats were anesthetized with
      halothane and a segment of the thoracic aorta removed. Aortic rings measuring 1.6
      2.0 mm in length were mounted in a water bath and stretched to optimal diameter.
      Aortic rings from control rats demonstrated a 57% increase in maximum contraction
      to phenylephrine and a 68% increase to KCl compared to aortic rings from rats
      with sepsis (p < .01). There was no difference in the concentrations of
      phenylephrine or KCl which elicited a half-maximal contraction (EC50) in control
      versus septic aortic rings. Removal of the endothelium increased the sensitivity
      of aortas to both phenylephrine and KCl in septic and control aortic rings but
      did not reverse the defects in contraction in sepsis. Treatment of the aortic
      rings with N gamma-nitro-L-arginine methyl ester (L-NAME), a nitric oxide
      synthase inhibitor, increased contraction in aortic rings from both septic and
      control rats but also failed to correct the contractile defect in sepsis. The
      frequency and amplitude of the oscillations in wall tension which occurred with
      phenylephrine were slower, i.e., .07 +/- .10 vs. .17 +/- .02 Hz, for septic and
      control rings, respectively (p < .05), and had a greater amplitude .65 +/- .01
      vs. .41 +/- .09 mN/mm, for septic and control rings, respectively (p <
      .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728583
TI  - Contractile dysfunction of ventricular myocytes isolated from endotoxemic guinea
      pigs.
AB  - Mechanisms responsible for the decline in cardiac function following sepsis or
      endotoxemia are unclear but may result from indirect effects of cardiodynamic
      readjustments to diminishing venous return or to direct effects of endogenous
      factors on myocardial function. We examined contractile properties of ventricular
      myocytes isolated from endotoxemic guinea pig hearts to 1) verify and
      characterize inotropic dysfunction in the absence of immediate influences from
      extrinsic neurohumoral agents, and 2) assess the ability of beta-adrenergic
      receptor activation to modulate contractility. Myocytes were isolated by
      enzymatic dispersion from hearts 4 h following an intraperitoneal injection of
      Escherichia coli endotoxin. Contractility was assessed using a computer-driven
      image analysis system. Inotropic responsiveness of endotoxemic myocytes to
      changes in frequency of stimulation (.2-2.0 Hz) or increases in extracellular
      calcium ([Ca2+]o, 1.8-8.0 mM) was significantly less than control myocytes, even
      with maximally effective frequencies or [Ca2+]o. These data demonstrate that the
      endotoxin-induced dysfunction is intrinsic to ex vivo cardiac myocytes and
      independent of immediate influence from extracardiac factors by 4 h in vivo
      exposure to endotoxemia. Inotropic responsiveness to beta-adrenergic receptor
      activation remained intact in endotoxemic myocytes; maximally effective
      concentrations (> 10 nM) reversed the endotoxin-induced contractile dysfunction.
      These data confirm that E. coli endotoxemia incorporates intrinsic contractile
      dysfunction of myocardial cells, while sparing their ability to respond to
      inotropic mechanisms activated by beta-adrenoceptor agonists.

PMID- 7728584
TI  - Vagal innervation influences the whole body oxygen consumption-delivery
      relationship in the dog.
AB  - Vagotomy alters regional blood flow distribution by interrupting the tonic
      central inhibitory effect of cardiopulmonary vagal afferent nerves on sympathetic
      outflow predominantly to the renal, splanchnic, and cutaneous circulations. We
      hypothesized that the alteration of blood flow distribution by vagotomy would
      lead to disruption of the oxygen consumption-oxygen delivery relationship
      (VO2/DO2), increase critical DO2 (DO2Crit), and decrease whole-body oxygen
      extraction ratio (O2ER). Nineteen chloralose-anesthetized, paralyzed,
      splenectomized dogs were submitted to either bilateral vagosympathectomy (n = 7),
      bilateral vagotomy (n = 6), or sham denervation (n = 6) following baseline
      cardiorespiratory parameter measurement. VO2 was measured by indirect calorimetry
      and carotid blood flow by ultrasonic flow probe. Incremental hemorrhages (1-5
      mL/kg) were performed to determine the VO2/DO2 relationship. Cardiorespiratory
      parameters were measured after each hemorrhage at steady-state VO2. DO2Crit was
      derived from the VO2/DO2 relationship using a best-fit regression analysis
      technique. The average DO2Crit values of the vagotomy (9.1 +/- .54) and
      vagosympathectomy (11.5 +/- 1.2 mL/min/kg) groups were significantly greater than
      the control group (7.72 +/- .43). After hemorrhage had been performed to a point
      that decreased mean arterial pressure to approximately 70 mmHg from baseline
      values, carotid blood flow in the vagosympathectomy group was significantly
      greater than the control group. We conclude that vagotomy disrupts the VO2/DO2
      relationship. Vagosympathectomy causes a severe disruption of the VO2/DO2
      relationship, probably by the combined effect of vagotomy and interruption of
      sympathetic nervous system control of blood flow to the head and neck.

PMID- 7728585
TI  - Hepatic neutrophil sequestration in early sepsis: enhanced expression of adhesion
      molecules and phagocytic activity.
AB  - Abdominal sepsis was produced by cecal ligation and puncture (CLP) in rats to
      observe neutrophil (PMN) migration into the liver and assess the functional
      alteration in circulating PMNs, liver sequestered PMNs, and Kupffer cells. 7 h
      following CLP, rats demonstrated severe leukopenia and major amount of PMNs
      sequestered into the liver (17.0 +/- 5.5 x 10(6) vs. 3.1 +/- 1.6 x 10(6) in sham
      operated rats, p < .01). Light microscopic evidence demonstrated the presence of
      such PMNs in the sinusoids and in the liver parenchyma. By 20 h following CLP,
      the number of PMNs in the liver was not different from sham controls. CD11b/c
      expression on circulating PMNs was significantly upregulated from 1.6 +/- .3 to
      7.8 +/- .9 mean channel fluorescence (MCF) in 7 h CLP rats. Liver-sequestered
      PMNs showed further enhancement of CD11b/c expression to 10.4 +/- 1.9 MCF than
      the circulating PMNs. However, in the late septic rats, CD11b/c expression on
      circulating PMNs 2.9 +/- .5 MCF returned to the control level of 1.9 +/- .7 MCF.
      Liver-sequestered PMNs and Kupffer cells in septic rats exhibited remarkably
      enhanced phagocytic activities 53.0 +/- 10.8 and 56.9 +/- 7.7% phagocytosis,
      respectively, regardless of the suppression of phagocytosis in circulating PMNs
      (16.0 +/- 5% phagocytosis). In 7 h CLP rats, liver-sequestered PMNs exhibited a
      significantly higher level of superoxide anion generation 21.8 +/- 12.2 nmol/30
      min/10(6) cells than did Kupffer cells (4.2 +/- 3.0 nmol/30 min/10(6) cells).
      These results demonstrate that the liver is a target organ for neutrophil
      sequestration during the septic response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728586
TI  - Thiol reducing agents modulate induced apoptosis in porcine endothelial cells.
AB  - When cultured porcine endothelial cells are exposed first to endotoxin
      (lipopolysaccharide (LPS)) followed by standard inducers of the heat shock
      response in vitro (heat or sodium arsenite), these cells aberrantly execute
      programmed cell death. This cell death is dependent upon two distinct events: the
      LPS-priming step and the heat shock-induced activation step. Prior work
      demonstrated that the LPS-priming step could be blocked by the prior application
      of cell-permeable hydroxyl radical scavengers, suggesting a role for this
      reactive oxygen species as an important intracellular signal mediating the first
      step. In these present experiments, we evaluated the potential role of reduction
      oxidation mechanisms in the heat shock activation step. The thiol reducing agents
      reduced glutathione (GSH), n-acetylcysteine (NAC), and dithiothreitol (DTT) were
      evaluated for their ability to block programmed cell death in LPS-primed porcine
      aortic endothelial cells. Both DTT and NAC, agents that augment intracellular
      reduced glutathione levels, were protective against cell death when applied prior
      to heat shock induction with sodium arsenite (As) in endothelial cells treated
      previously with LPS. The less cell permeable agent GSH was not protective.
      Delayed application of DTT or NAC could block progression to cell death for up to
      1.5 h after initiation of the heat shock response with As. These data show that
      heat shock-induced programmed cell death in LPS-primed endothelial cells can be
      arrested, at least in its early stages, by agents that augment or stabilize the
      reducing potential of the cell.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728587
TI  - Pentoxifylline improves the tissue oxygen extraction capabilities during
      endotoxic shock.
AB  - Pentoxifylline (PTX), a xanthine derivative used in the treatment of circulatory
      insufficiency, has been found to have protective effects in different models of
      sepsis. We hypothesized that this drug might improve the cellular oxygen
      availability following endotoxin challenge by increasing oxygen delivery (DO2)
      and/or tissue oxygen extraction. The oxygen extraction capabilities were studied
      during a reduction in blood flow induced by cardiac tamponade. Fourteen
      anesthetized, ventilated, and paralyzed dogs, received intravenous 2 mg/kg of
      Escherichia coli endotoxin followed by a continuous infusion of 20 ml/kg.h of
      saline. 30 min later tamponade was induced by repeated bolus injections of warm
      saline into the pericardial space. Seven dogs were pretreated with PTX as an
      intravenous bolus of 20 mg/kg, followed by a continuous infusion at 20 mg/kg.h,
      and the other seven dogs served as a control group. PTX largely attenuated the
      systemic and pulmonary vasoconstriction observed in the control group and
      resulted in significant increases in cardiac index, DO2 and oxygen consumption
      (VO2). PTX also improved ventilation/perfusion matching in the lungs as indicated
      by a higher PaO2 and PvO2 and a lower venous admixture than in the untreated
      group during cardiac tamponade (both p < .05). In addition, the critical DO2 (DO2
      crit) was lower and the critical oxygen extraction ratio was higher in the PTX
      treated than in the control group (9.1 +/- 1.8 vs. 11.6 +/- 2.4 ml/kg.min, and
      70.6 +/- 14.0 vs. 49.3 +/- 14.6%, both p < .05). The VO2/DO2 dependency slope was
      also steeper in the PTX-treated than in the control group (.80 +/- .28 vs. .43 +/
      .19, p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728588
TI  - Effects of cholinergic blockade on hemodynamic disturbances and intestinal
      lesions in endotoxic shock in newborn piglets.
AB  - The parasympathetic nervous system actively participates in the regulation of
      pathophysiologic responses in circulatory shock. To determine the effects of
      cholinergic blockade in endotoxic shock in newborn piglets, 16 chronically
      instrumented newborn piglets were infused with 10 mg/kg of endotoxin over 10 min.
      Eight animals were injected intravenously with 10 mg/kg of anisodamine, an
      anticholinergic drug, 10 min before endotoxin and then with escalating doses of
      2, 5, 10, and 20 mg/kg every 10 min, beginning 60 min after endotoxin. The other
      eight animals were given saline as a control. Endotoxin infusion caused
      elevations in mean pulmonary artery pressure and vascular resistance index and an
      initial increase in systemic artery pressure followed by hypotension. Heart rate
      was stable for 45 min and then increased. Cardiac index fell from a baseline of
      173 +/- 20 (mean +/- S.E.) to 136 +/- 23 mL.min-1.kg-1 60 min after endotoxin.
      Pretreatment with anisodamine increased heart rate from 163 +/- 15 to 289 +/- 10
      beats.min-1 and cardiac index from 195 +/- 15 to 238 +/- 14 mL.min-1.kg-1 before
      endotoxin infusion. These variables remained at higher levels than in the control
      group until 60 min after endotoxin infusion; thereafter, the two groups were
      similar. The changes in pulmonary and systemic artery pressures were not
      significantly altered by anisodamine. After 60 min, additional doses of
      anisodamine caused no significant hemodynamic responses, and the differences
      between the two groups were not significant. Arterial plasma thromboxane B2
      levels rose immediately and tumor necrosis factor-alpha levels increased 60 min
      after endotoxin infusion; no significant differences were noted between groups at
      any time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728589
TI  - The ethics of nursing care and 'the ethic of care'.
AB  - Recent discussions concerning the ethics of nursing care have gained added
      impetus from articulations of the so-called 'ethic of care' in moral philosophy.
      This paper addresses the question of recognizing and elaborating the ethics of
      nursing care by exploring the problems and the possibilities of these
      intersecting discourses. In the first part of the paper it is argued that
      appropriation of 'the ethic of care' by nursing theorists as the central value of
      nursing, in contradistinction to other moral values such as beneficence or
      justice, runs the risk of reinforcing the conventional approaches to ethics that
      'the ethic of care' seeks to overturn. Central to 'the ethic of care' is the
      recognition that caring entails a focus on the particularities and context of the
      relationships in which it is expressed. Accordingly the application of a unitary
      concept of care to the context of nursing relations may seriously distort their
      diverse and complex-specific ethical possibilities. The dynamic complexity of
      nursing ethics may be more adequately understood by working through an array of
      specific examples of nursing practice highlighting the differences and
      similarities between them and other ethical practices of care. Experience of a
      set of examples in this way will draw attention to the multiplicity, ambiguity,
      and particularity of the ethics of nursing care. In the second part of the paper
      a beginning is made on this project by addressing the work of several different
      theorists of care who have examined different practices of nursing from the
      overlapping perspectives of nurses, patients and the socio-historical
      construction of their relationships.

PMID- 7728590
TI  - Madness in our methods: nursing research, scientific epistemology.
AB  - This paper is a critique of some research methods evident in contemporary nursing
      literature. The arguments derive from critical-feminist, humanist and ethical
      perspectives. As a consequence of investigating specific aspects of scientific
      method, an approach to research that is congruent with values intrinsic to an
      holistic approach to nursing practice is articulated. Such methodologies also
      render problematic with status quo power relations between nurses and other
      health professionals, as well as between nurses and patients. The central themes
      in this paper are: the absence of overt conceptual frameworks; an avoidance of
      complex social contexts within which research subjects live; an apparent lack of
      empathy; and an apolitical articulation of research problems and data analyses.
      All four of these difficulties may be traced to scientific methodology by many
      researchers. Most nurse researchers may not actually adhere to this technique,
      but I propose that they have been informed by belief systems associated with
      scientific methodology and that these have dire consequences for the discipline
      of nursing. A key argument is that the apparent lack of conceptual frameworks in
      the majority of nursing research is due to the epistemology, which therefore
      provides a pre-existing, non-declared conceptual framework, that is incorporated
      into the research by drawing upon scientific methodology. A further argument is
      that scientific, or scientistic, ways of approaching situations are antithetical
      to nursing values and to constructive social change for the benefit of patients,
      nursing and nurses.

PMID- 7728591
TI  - The impact of postmodernism on research methodology: implications for nursing.
AB  - This article considers what have been referred to as the two major crises in
      research methodology: (i) the crisis of legitimation (to what extent are the
      notions of reliability and validity still meaningful in the light of a posture
      that is said to approach an 'anything goes' standpoint); and (ii) the crisis of
      representation (to what extent is it possible to represent the world view of 'the
      other' without it being merely a construction of the researcher). These are
      discussed in order to identify aspects of a continuing debate that is of
      relevance to nurses for they are integral to graduate research and the ongoing
      application of research in hospital or community contexts. Educating nurses in
      research requires that they learn a repertoire of research skills such as
      literature critiques, developing research questions, interviewing, analysing
      techniques and computer-assisted analysis. However, postmodern debates can also
      be beneficial by facilitating their understanding of contemporary research issues
      so that they can critically integrate such reflexive thinking into their own
      research practices and go on to explore new ways to undertake research.

PMID- 7728592
TI  - A magnificent chaos: feminist (nursing) comments on Western philosophy.
AB  - This paper primarily concerns feminists' problems with Western philosophy and the
      implications of these for nursing. My interest arises from some reading of
      philosophy and a profound disenchantment with its male bias. As Susan Moller Okin
      says, readers should not be misled by the use of supposedly generic terms like
      'mankind' and allegedly inclusive pronouns, into thinking philosophers intended
      to refer to the whole human race. Moira Gatens takes the view that feminists
      cannot ignore the frameworks and assumptions of traditional philosophy and
      identifies three major ways in which the relationship between feminist theory and
      philosophical discourse can be characterized. In contrasting Gatens' thesis with
      a nursing case in point about ways of viewing disciplines, some ideas emerge for
      nurses to find positive ways forward in the philosophical enterprise. The topic
      extends to feminists' reactions to postmodern thinking and subsequent questions
      raised by these for nurses and nursing.

PMID- 7728593
TI  - Humanism in nursing: the emergence of the light.
AB  - This paper examines Western nursing practices by focusing on their spiritual
      aspect. The transformation of the informal and poorly trained nurse into the
      trained and uniform persona of the modern nurse is the subject of many nursing
      histories and part of nursing mythology. Using the work of Michel Foucault and
      Marcel Mauss, the nursing that preceded the 19th century reformers is re-examined
      and continuities between current and quite ancient practices of nursing are
      explored. The development of practices or technologies for care of the sick
      originated with the establishment of hospitals in the 4th century as part of
      pious Christian practice. Current practices of care and the discourse of holistic
      nursing are argued to have grown from these traditional Christian technologies of
      care. Humanist or holistic nursing represents the enshrinement of the Christian
      ethos--freed of doctrine; the discourse of caring a redrafted Christian
      discipline of love.

PMID- 7728594
TI  - Reshaping ethnography: contemporary postpositivist possibilities.
AB  - Following Leinginger's introduction of ethnography into the field of nursing
      research, numerous descriptive and interpretive studies of health care beliefs
      and practices have been conducted. The resultant data have been translated into
      recommendations relative to the areas of nursing education, administration and
      clinical practice in an effort to ensure that the identified cultural needs are
      recognized and met. In this paper the discourses that inform such work are
      explored. Its practices and emergent dilemmas are reassessed in the light of an
      emerging body of work that challenges its foundational assumptions. Linked under
      the umbrella of 'postpositivist ethnography', such work recognizes the research
      area as a social and political field of which the researcher is an integral part.
      Hence, as an informed subject, the researcher, like the informants, is seen to be
      implicated in the generation of data. She, or he, is not charged with occupying
      the opposing roles of objective researcher and subjective participant, nor with
      reporting 'the truth' as told by informants. This emergent tradition is not
      without its dilemmas and of particular concern is the issue of authority; that
      is, whose voice constructs the text? As nursing academics grapple with questions
      regarding the nature of the knowledge that informs their discipline, it is
      imperative that they critique potentially fruitful research practices before they
      appropriate them. Failure to do so may lead them to unwittingly generate
      knowledge that is inimical to their particular quest. The 'new ethnography'
      discussed in this paper, offers academics and others interested in the generation
      of knowledge, not only a methodology that invites the possibility of opening up
      previously hidden areas of practice, but one that actively involves the
      researcher in challenging her taken-for-granted assumptions.

PMID- 7728595
TI  - Hildegard Peplau in a conversation with Mark Welch. Part I.

PMID- 7728596
TI  - Response: to be or not to be? Nurse? Researcher? Or both?

PMID- 7728597
TI  - [Pain and AIDS].

PMID- 7728598
TI  - [Evaluation of laryngeal masks].
AB  - The size 1 laryngeal mask (LMA1) was studied prospectively in a series of 37
      infants (weight less than 6.5 kg) undergoing 42 routine surgical procedures. LMA1
      insertion was successful at first attempt in 80.9% of all cases and a good airway
      control was obtained in 93%. The most frequent cause of insertion failure was an
      insufficient depth of anaesthesia. Only one incident occurred peroperatively. The
      recovery incidents rate, higher than in other studies, was mainly due to the
      laryngeal hyperreactivity of infants. LMA1 provides high safety for infant
      anaesthesia woith food working conditions for bot anaesthetist and surgeon.
      However, an accurate determination of the anaesthesia level and a close
      monitoring of recovery are strongly recommended.

PMID- 7728599
TI  - [Comparative study of propofol versus thiopental-halothane in the occurrence of
      oculocardiac reflex and postoperative vomiting after surgery for strabismus in
      children].
AB  - Strabismus surgery in children is associated with side-effects, intraoperative
      oculocardiac reflexes in relation with muscular tractions and postoperative
      vomiting. Studies with propofol anaesthesia in this surgery have shown a lower
      incidence of these side-effects. So, a prospective study compared these
      incidences with propofol (P) versus thiopental/halothane (T+H) anaesthesia.
      Propofol appears to be efficient in reducing postoperative vomiting but might be
      associated with more frequent OCR.

PMID- 7728600
TI  - [Value of dobutamine in children surgically treated for portal hypertension.
      Apropos of 23 cases].
AB  - In children undergoing mesenterico-caval or distal spleno-renal shunting for
      extrahepatic portal hypertension, dobutamin (3-5 micrograms.kg-1.min-1 for 24 hr
      postoperatively) prevents right ventricle dysfunction and pulmonary hypertension
      resulting from suddenly increased blood return to the heart by the inferior vena
      cava, thus improving cardiac output and myocardial contractility. Twelve 1-15 yr
      children benefitted from this inotropic therapy without any adverse side effect.

PMID- 7728601
TI  - [Mechanical ventilation during MRI in children. Anesthetic constraints].
AB  - Early use of magnetic resonance imaging (MRI) excluded patients needing
      mechanical ventilation. However magnetic resonance imaging is an innocuous
      investigation and affords important elements to the diagnosis of many
      pathologies. Improvement of anaesthetic equipment have led to enlarge MRI
      applications considerably. Ventilations situated outside the MRI room required
      very long tubing, to 9-11 m. Although the ferromagnetic charge of presently used
      ventilators is greatly reduced, it is still necessary to keep them at some
      distance from the patient, with tubing of about 3 m, even in children. Therefore
      the compressible gas volumes are larger than the usual ones. For a tube length of
      3 m, about 2-3 ml.kg-1 should be added to the standard tidal volume (10 ml.kg-1),
      so as to obtain safe normoventilation.

PMID- 7728602
TI  - [Anesthesia for lithotripsy].
AB  - Extracorporeal shock wave lithotripsy has become the standard method of treating
      renal stone disease. The appropriate choice of anaesthetic technique depends on
      the shock wave technic mode. Recent modifications of lithotriptors have reduced
      the physiological consequences of the procedure and most often these treatments
      can be performed without local or general anaesthesia. However, some
      sedation/analgesia may be necessary and a good knowledge of anaesthesia for
      lithotripsy remains most useful so as to meet any particular requirements.

PMID- 7728603
TI  - [Polytraumatized burnt patients].
AB  - In peace time, burn injury combined with traumatic, chemical or radioactive
      casualties, is rarely encountered and often unrecognised; during disasters, burn
      injury is unlikely the only trauma. The authors try to bring out the great
      physiopathologic, diagnostic and therapeutic principles of changes due to
      combined lesions on burn injury and vice-versa.

PMID- 7728604
TI  - [Platelet concentrates: types, costs and indications].
AB  - Platelet transfusion is a widely used form of therapy and a sound knowledge of
      its basic principles is essential to obtain the required efficacity while
      assuring optimal security for the patients. Platelet concentrates (PC) may
      originate from two types of blood donation: whole blood donation or apheresis. In
      the first case, the platelets are separated in sterile closed systems following
      withdrawal of blood from group A or O donors. These so-called "standard" PC (SPC)
      are most often delivered in the form of mixtures constituting the PC from several
      donations. In the second case, the platelets are separated from the red blood
      cells in the course of plasmapheresis or cytapheresis. Generally, these apheresis
      PC originate from a single donor, except in some cases where the PC from two
      plasmapheresis donations may be combined. The French Blood Authorities have
      recently recommended an increase in the proportion of apheresis PC (monodonor)
      with respect to PC mixtures from several donors, essentially in order to further
      increase the security against viral contamination. At present, PC are not
      subjected to viral destruction treatment. In recent times, a number of
      transfusion centres have introduced systematic determination of the platelet
      count and volume in all PC delivered, thus enabling inscription on the bag label
      of the total quantity of platelets (active ingredient) contained in the bag (1
      unit = 0.5 x 10(11) platelets). This is useful to calculate the index of platelet
      recovery after transfusion and to detect refractory states.

PMID- 7728605
TI  - [Pasteurella multocida septicemia. Apropos of a case].

PMID- 7728606
TI  - [HELLP syndrome and pregnancy hypertension: severity? Anesthetic management].
AB  - Four cases of HELLP Syndrome (Haemolysis, Elevated liver enzymes, Low Platelet
      count) (HS) have given the authors an opportunity for this brief review. HS
      should be evoked in any pregnant woman with high blood pressure during the last
      term, for it is a real emergency. Symptomatic treatment and rapid extraction
      constitute the commonly accepted therapy, by which maternal and foetal morbidity
      and mortality can be considerably reduced.

PMID- 7728607
TI  - [Pancytopenia caused by folate deficiency during pregnancy].

PMID- 7728608
TI  - [Emergency and general practitioners].

PMID- 7728609
TI  - [Emergency admission in hospitals].

PMID- 7728610
TI  - [Combined epidural and spinal anesthesia for cesarean section].
AB  - Combined spinal epidural block has proven its efficacy in skilled hands. This
      technique allies advantages of spinal anaesthesia, regarding its speed of action
      and intensity of motor blockade and advantages of postoperative epidural
      analgesia. This block must be performed with great care and method to reach a
      success rate of almost 100%. Local anaesthetics and additives are reviewed and
      commented. The two main complications, hypotension and post dural puncture
      headache can be contained in very low limits.

PMID- 7728611
TI  - [Psychiatric emergency and anesthesiology].

PMID- 7728612
TI  - [The art of reasonable combining drugs in anesthesia].
AB  - As yet no single intravenous anaesthetic drug can effectively and safely provide
      hypnosis, analgesia and amnesia. Thus intelligent combinations of hypnotics and
      opioids are necessary, especially for total intravenous anaesthesia (TIVA).
      Inescapable interactions occur, most of which are synergistic and should be
      evaluated for the optimal care of the patient. This synergism varies considerably
      according to the different drugs, the different endpoints of anaesthesia and the
      differently combined dosage of both agents. Because of their complex
      pharmacological properties, a valuable approach to evaluating interactions
      consists in administering both drugs to known plasma concentrations with the help
      of pharmacokinetic model-driven drug delivery systems (computer assisted
      continuous infusion). The Cp50 concept (plasma concentration that will prevent a
      pre-defined response to a given stimulus in 50% of the patients) is of prime
      interest. Recent (and current) studies have tried to define Cp50s of various
      hypnotics (such as propofol) and opioids (fentanyl, alfentanil, sufentanil). The
      best IV delivery technique appears to be infusing an opioid drug at analgesic
      concentrations (1-3 ng.ml-1 for fentanyl) and the hypnotic drug at modulated (but
      always hypnotic, no less than 3.0 micrograms.ml-1 for propofol) concentrations
      according to the different surgical stimuli and the patient's responses. The
      opposite approach (fixed hypnotic concentration, varying analgesic concentration)
      would be much less satisfactory. In addition, preoperative medications should be
      taken into account. Thus a better knowledge of the type and degree of
      interactions, as in a well-administered inhalational anaesthesia supplemented by
      opioids, will very likely contribute to develop TIVA liability and popularity.

PMID- 7728613
TI  - [Restructuring of emergency services: "hopes and anxieties"].

PMID- 7728614
TI  - [Strategy of erythrocyte transfusion and plasma use in traumatic emergencies].

PMID- 7728615
TI  - [Spinal anesthesia in Africa. Risks, precautions].
AB  - Practice of anaesthesia in Africa rural zones needs adaptation to its
      peculiarities: pathology abundance, equipment and skilled staff shortage, medical
      and surgical acts delegation. It is high risk anaesthesia to do in a perspective
      of public health. Spinal anaesthesia, simple and cheap, is the technique of
      choice used for 86% of operations in our hospital. However it may induce
      sympathetic tone abolishment with marked falls in blood pressure and even cardiac
      arrest. To suppress the part of chance in this high risk context, we have made
      repetitive sympathetic perturbations prophylaxis, thanks to 2 protocoles. One
      issued from "saddle-block" allows genital and below surgery. Main worry is to get
      sure sensitive level, below D10. We use hyperbare technique, so blood pressure
      falls are less than 5%. The other is for abdominal surgery. Main worry is
      hypotension prophylaxis and management. We use hypobare technique, which allows
      Trendelenburg position with low cost and low risk autotransfusion. Other measures
      to reduce incidence of hypotension include prophylactic administration of
      atropine, ephedrine, and oxygen during the installation of anaesthesia.

PMID- 7728616
TI  - [Anesthesia in severely burnt patients: a 10-year experience].
AB  - A retrospective study of our anaesthesiologic activity during the decade 1982
      1991 concerning 314 severely burned patients (53.4% of all the hospitalizations)
      submitted to escharrectomy with cutaneous grafts showed a greatest incidence in
      1990 (19.5% of all the interventions) mostly for 12 to 60 year-old patients. In
      51% of all cases, patients had burns over less than 30% of the body surface. 76%
      got a combined general anaesthesia mainly by isoflurane (68%) and 24%, especially
      0 to 12 year-old patients (63.1%), a monopharmacological anaesthesia by ketamine.

PMID- 7728617
TI  - [Facing emergency in medicine].

PMID- 7728618
TI  - [Reorganization of emergencies: current concept and reality].

PMID- 7728619
TI  - Aspirin-induced early and late asthmatic response.

PMID- 7728620
TI  - Asthma and anaphylaxis: a relevant model for chronic disease? An historical
      analysis of directions in asthma research.

PMID- 7728621
TI  - Allergen nomenclature. WHO/IUS Allergen Nomenclature Subcommittee World Health
      Organization, Geneva, Switzerland.

PMID- 7728622
TI  - Early and late onset asthmatic responses following lysine-aspirin inhalation in
      aspirin-sensitive asthmatic patients.
AB  - Inhalation of aerosolized lysine-aspirin (L-ASA) has been described as an
      alternative diagnostic method in aspirin-sensitive asthma. To further understand
      the pathogenetic mechanism of aspirin-sensitive asthma, we performed L-ASA
      (Inyesprin) bronchoprovocation test (BPT) in 51 asthmatic patients (45 non-atopic
      and six atopic asthma). Twenty-six patients showed significant
      bronchoconstriction after the inhalation of L-ASA. Bronchoprovocation test
      produced immediate asthmatic responses in 13 cases as well as dual asthmatic
      responses in four cases, whose late onset asthmatic response was noted at 4-7 h
      after L-ASA inhalation. We conclude that L-ASA bronchoprovocation might be a
      useful method for the diagnosis and investigation of aspirin-sensitive asthma.
      However, L-ASA inhalation can also induce late onset asthmatic responses.

PMID- 7728623
TI  - Human exposure to environmental pollutants: a decade of experience.

PMID- 7728624
TI  - Mast cell distribution and neutral protease expression in acute and chronic
      allergic conjunctivitis.
AB  - Allergic eye disease has a variety of clinical manifestations including seasonal
      atopic conjunctivitis (SAC), perennial atopic conjunctivitis (PAC), atopic
      keratoconjunctivitis (AKC), and atopic blepharoconjunctivitis (ABC). We have
      investigated the number, distribution and protease expression of mast cells in
      normal and diseased conjunctiva with the use of immunohistochemistry in water
      miscible resin sections. The median mast cell densities in normal subjects were
      17 mm-2 in the bulbar substantia propria and 9 mm-2 in tarsal substantia propria.
      Mast cells were absent from the normal conjunctival epithelium at both sites.
      Mast cell densities were increased in the bulbar substantia propria in SAC, AKC
      and ABC. Tarsal substantia propria showed a significant increase in mast cells in
      ABC and AKC disease states. Mast cells express a range of proteases which varies
      according to their anatomic site. Mast cells in connective tissue are described
      to contain tryptase, chymase, cathepsin-G and carboxypeptidase-A, whereas mucosal
      mast cells contain only tryptase. In the diseased conjunctiva there was a marked
      reduction in proteases other than tryptase in the intraepithelial mast cells.
      There were also significant reductions in protease expression other than tryptase
      in the bulbar substantia propria in AKC and ABC. There appear to be specific
      alterations in the distribution of mast cells in the sub-categories of allergic
      eye disease. The distinction between mucosal and connective tissue mast cell
      phenotypes is not clear-cut and may depend on the functional state of the mast
      cells in relation to the microenvironment.

PMID- 7728625
TI  - Bronchial hyperresponsiveness and airway neutrophil accumulation induced by
      interleukin-8 and the effect of the thromboxane A2 antagonist S-1452 in guinea
      pigs.
AB  - Interleukin-8 (IL-8) has been shown to be a chemotactic factor for neutrophils, T
      lymphocytes and eosinophils, but it is unknown whether the IL-8-induced
      inflammatory cell accumulation into the airways can cause the bronchial
      hyperresponsiveness (BHR) characteristic of asthma. IL-8 at a dose of 0.5 or 5
      micrograms/kg was administered intranasally to guinea-pigs twice a week for 3
      weeks. One day after the last administration, animals were anesthetized and
      artificially ventilated through tracheal cannula and lateral pressure at the
      cannula (Pao) was measured as an overall index of airway responses to increasing
      concentrations of inhaled histamine (25, 50, 100, and 200 micrograms/ml). The IL
      8 treatment significantly enhanced bronchial responsiveness to histamine in a
      dose-dependent manner (ANOVA P < 0.01). The provocative concentration of
      histamine causing a 100% increase in Pao (PC100) at a dose of 0.5 and 5
      micrograms/kg of IL-8 was 68.1 (GSEM 1.12) and 35.6 (GSEM 1.25) micrograms/ml,
      respectively. The latter was significantly (P < 0.01) lower than that in control
      animals treated with PBS (93.3 [GSEM, 1.14] micrograms/ml). The IL-8 treatment
      also induced a significant influx of neutrophils, but not eosinophils, in
      bronchoalveolar lavage (BAL) fluid (18.3 +/- 8.8 and 30.6 +/- 8.3% in animals
      treated with 0.5 and 5 micrograms/kg, respectively, of IL-8 vs 3.6 +/- 0.7% in
      phosphate buffered saline-(PBS)-treated animals). Furthermore, we examined the
      effect of the thromboxane receptor antagonist S-1452 (0.01 or 0.1 mg/kg, i.p. 24
      and 1 h before anesthesia) on this IL-8 induced BHR. S-1452 significantly
      inhibited the BHR dose-dependently (ANOVA P < 0.001).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7728626
TI  - Blood inflammatory response to inhaled endotoxin in normal subjects.
AB  - Previously we have reported that in asthmatics an inhalation of 20 micrograms
      lipopolysaccharide (LPS) produces a bronchial obstruction associated with an
      inflammatory blood response. The aim of the present study was to evaluate this
      response in normal subjects. Eight normal non-atopic subjects were challenged by
      inhalation of a solution containing 20 micrograms LPS (from Escherichia coli
      026:B6) a week after bronchial challenge with control solution. The lung function
      response was evaluated by the changes in forced expiratory volume in one second
      (FEV1), in specific conductance and in airway resistance while the blood
      inflammatory response was evaluated by serial measures of total white blood cells
      (WBC) and polymorphonuclear neutrophils (PMN) count, luminol enhanced
      chemiluminescence (luminol-CL, as a marker of the PMN degree of activation), C
      reactive protein (CRP), haptoglobin, complement fraction C3, tumour necrosis
      factor-alpha (TNF-alpha) and adrenocorticotropic hormone (ACTH). No response in
      lung function was observed for 6 h after the LPS inhalation. The count in WBC and
      PMN increased 300 (P < 0.01) and 360 (P < 0.01) min after the LPS challenge
      associated with an increase in the level of luminol-CL (P < 0.001). This rise in
      luminol-CL level was significant at 120 min (P < 0.05) before any change in the
      PMN count. After 24 and 48 h the acute-phase protein CRP raised significantly (P
      < 0.01), the other proteins C3 and haptoglobin being unchanged. A slight increase
      in ACTH was observed 240 and 360 min (P < 0.05) after the LPS challenge while the
      TNF alpha detectable level was not modified.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728627
TI  - Chronic asthma and chiropractic spinal manipulation: a randomized clinical trial.
AB  - The purpose of this randomized patient- and observer-blinded cross-over trial was
      to evaluate the efficacy of chiropractic treatment in the management of chronic
      asthma when combined with pharmaceutical maintenance therapy. The trial was
      conducted at the National University Hospital's Out-patient Clinic in Copenhagen,
      Denmark. Thirty-one patients aged 18-44 years participated, all suffering from
      chronic asthma controlled by bronchodilators and/or inhaled steroids. Patients,
      or who had received chiropractic treatment for asthma within the last 5 years,
      who received oral steroids and immunotherapy, were not eligible. Patients were
      randomized to receive either active chiropractic spinal manipulative treatment or
      sham chiropractic spinal manipulative treatment twice weekly for 4 weeks, and
      then crossed over to the alternative treatment for another 4 weeks. Both phases
      were preceded and followed by a 2-week period without chiropractic treatment. The
      main outcome measurements were forced expiratory volume in the first second
      (FEV1), forced vital capacity (FVC), daily use of inhaled bronchodilators,
      patient-rated asthma severity and non-specific bronchial reactivity (n-BR). Using
      the cross-over analysis, no clinically important or statistically significant
      differences were found between the active and sham chiropractic interventions on
      any of the main or secondary outcome measures. Objective lung function did not
      change during the study, but over the course of the study, non-specific bronchial
      hyperreactivity (n-BR) improved by 36% (P = 0.01) and patient-rated asthma
      severity decreased by 34% (P = 0.0002) compared with the baseline
      values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728628
TI  - Report on 'Medical and surgical management of rhinitis' course.

PMID- 7728629
TI  - Protozoal causes of reproductive failure in domestic ruminants.
AB  - Protozoan parasites are a significant cause of abortion and infertility in
      domestic ruminants. Toxoplasma gondii, a widespread cause of abortion in sheep
      and goats, and Sarcocystis spp., which cause a common, frequently asymptomatic
      infection of domestic ruminants, both have a two-host life cycle. Carnivorous
      definitive hosts spread the infection through their feces and domestic ruminants
      are intermediate hosts. A similar, recently recognized protozoa, Neospora sp.,
      has emerged as an important cause of reproductive disease, especially as an
      abortifacient in dairy cattle. Neospora is presumed to also have a two-host life
      cycle, although the definitive host(s) has not been identified. The venereally
      transmitted Tritrichomonas foetus is an important cause of pregnancy loss in
      naturally bred cattle throughout the world. In the absence of effective methods
      for vaccination or treatment, control of these parasites is based on management
      procedures to reduce infection and transmission.

PMID- 7728630
TI  - Leptospirosis as a cause of reproductive failure.
AB  - Leptospirosis is a zoonotic disease caused by members of the genus Leptospira.
      Veterinarians' perceptions of leptospirosis as a disease of domestic animals has
      undergone considerable modification in the past decade or so because they have
      increasingly appreciated the role of the host-maintained leptospires as causes of
      reproductive wastage in their respective host species kept under modern intensive
      management systems.

PMID- 7728631
TI  - Ureaplasma diversum as a cause of reproductive disease in cattle.
AB  - This article includes a brief review of the classification, habitat, and
      characteristics of the ureaplasmas, followed by a discussion of the pathogenesis,
      transmission, clinical syndromes, diagnosis, immunity, and treatment of
      Ureaplasma diversum infections in cattle.

PMID- 7728632
TI  - Bacterial endotoxemia and reproductive effects in ruminants.
AB  - Gram-negative bacterial infections are fairly common in domestic ruminants. They
      can cause an endotoxemia with a variety of systemic signs, including fever,
      leukopenia, and ruminal stasis. Reproductive effects of endotoxemia include
      alterations in the estrous cycle and inability to maintain pregnancy. Diagnosis
      of endotoxemia is based largely on clinical evaluation. Confirming the diagnosis
      of endotoxin-induced reproductive alterations also is complicated by the lag
      period between clinical signs and abortion or infertility.

PMID- 7728633
TI  - Impact of bovine viral diarrhea virus on reproductive performance in cattle.
AB  - The major economic impact of BVDV infections is in producing reproductive
      dysfunctions. The virus can have a detrimental impact on the developing fetus at
      all stages, but the most severe consequences occur early in gestation. The virus
      is maintained in the bovine population through the production of PI offspring.
      Only the NCB biotype of the virus can produce PI calves. The NCB biotypes is the
      one that produces the vast majority of BVDV infections and, as a consequence, the
      greatest economic losses. Biotype and antigenic variation are two independent
      variables and vaccines should emphasise antigenic composition, not biotype. A
      BVDV control program that does not emphasize heifers is doomed to failure.

PMID- 7728634
TI  - Cache Valley virus.
AB  - Cache Valley Virus (CVV) is a causative agent of a mosquito-borne disease
      syndrome of sheep and, possibly, of all ruminants, characterized by embryonic and
      fetal death, stillbirths, and multiple congenital malformations. CVV is endemic
      in Canada, Mexico, and the United States. Several related Bunyaviruses also may
      play a role in syndromes of congenital malformations and embryonic losses in
      North America.

PMID- 7728635
TI  - Akabane virus.
AB  - Akabane virus, an arthropod-borne Bunyavirus, is the major cause of epizootics of
      congenital malformations in ruminants in Australia, Japan, Korea, and Israel, and
      is suspected to be a cause of sporadic outbreaks elsewhere. Blood-sucking
      insects, such as biting midges, transmit the virus horizontally to vertebrates.
      Climatic factors influence the seasonal activity and geographic range of the
      vector population and, therefore, occurrence of related disease. Inoculated
      ruminants seroconvert rapidly after a short subclinical viremia. Infection is of
      consequence only if ruminants are pregnant and not protected by adequate specific
      neutralizing antibodies. In naive pregnant animals, virus may spread
      hematogenously to replicate and persist in trophoblastic cells of placental
      cotyledons and subsequently invade the fetus. A distinct tropism for immature
      rapidly dividing cells of the fetal central nervous system and skeletal muscle
      results in direct virus-induced necrotizing encephalomyelitis and polymyositis.
      If fetuses survive, such injury may manifest as arthrogryposis, hydranencephaly,
      porencephaly, microencephaly, hydrocephalus, or encephalomyelitis at term. The
      earlier in gestation that fetal infection occurs, the more severe the lesions,
      reflecting the large population of vulnerable cells and lack of fetal
      immunocompetency at earlier stages of pregnancy. Injury during the period of
      critical cell migration and differentiation in organogenesis may substantially
      disrupt structural development in target organs. Late gestational infections
      cause nonsuppurative inflammation in the brain and spinal cord, premature birth,
      or fetal death with stillbirth or abortion. Affected neonates are nonviable.
      Control is by vaccination but is not always justified economically. Akabane viral
      infections must be differentiated from infections with other teratogenic viruses
      (including related Bunyaviruses), inherited conditions, and maternal
      intoxications. Diagnosis is made by serology and viral isolation.

PMID- 7728636
TI  - Bluetongue virus.
AB  - Bluetongue (BLU) is a noncontagious viral disease. The virus is a member of the
      Orbivirus genus and serves as the prototype virus of the genus. BLU is primarily
      a disease of domestic ruminants, some wild ruminants, and, recently, domestic
      dogs. The disease is caused by 1 of 24 different serotypes of virus that are
      distributed worldwide. This article reviews the viruses, their distribution,
      clinical signs, pathogenesis, and the roles they play in reproductive failure.

PMID- 7728637
TI  - Special tests for the diagnosis of infectious causes of reproductive failure in
      ruminants.
AB  - The detection of many infectious disease agents, including those of importance in
      ruminant reproductive failure, increasingly will be achieved through means other
      than the laborious and time-consuming traditional isolation and culture
      procedures. New diagnostic methodologies are designed both to enhance the
      rapidity with which results are obtained and to increase specificity and
      sensitivity of identification of the causative agent. Immunoenzyme histochemical
      staining of formalin-fixed paraffin-embedded tissues offers, especially in cases
      of abortions in which necropsy material routinely is examined histologically, an
      efficient and timely means of identifying many important pathogens. Antemortem
      serologic diagnostics will continue to be dominated by ELISA technologies. In the
      past decade, the specificity of serodiagnosis has been enhanced greatly by the
      use of monoclonal antibody-based competitive ELISA systems and further
      improvements in such methods will result from the use of defined antigens derived
      by recombinant DNA techniques. Although DNA hybridization technology has been
      applied successfully to detect many important veterinary pathogens and has been
      shown to have merit for improved diagnosis of some fastidious agents, those
      methods, because of their technical complexity, in general, have not been shown
      to be applicable for routine diagnostic uses. In contrast, methods using the PCR
      for specific gene amplification offer exceptional promise. Although the PCR
      presently is too technically exacting for routine use, its broad applicability
      and exquisite sensitivity and specificity suggest that it will play an ever
      increasing role in future veterinary diagnostic techniques.

PMID- 7728638
TI  - Effect of natural toxins on reproduction.
AB  - Poisonous plants grow in most plant communities found on rangelands and pastures.
      They are one of the principal causes of economic loss to the livestock industry.
      One major costly effect is on reproduction, which includes birth defects,
      abortions, lengthened calving intervals, and interference with oogenesis,
      spermatogenesis, libido, and estrus. Those plants that cause wasting, temporary
      illness, and other such effects can adversely effect reproduction livestock.

PMID- 7728639
TI  - CCS consensus conferences.

PMID- 7728640
TI  - Current status of silent myocardial ischemia.
AB  - A significant proportion of myocardial ischemia is 'silent' in nature.
      Furthermore, this asymptomatic ischemia portends an adverse prognosis for
      patients with known coronary artery disease. Silent myocardial ischemia can be
      objectively assessed and quantified by a number of noninvasive means; however,
      ambulatory electrocardiographic monitoring has emerged as a preferred method for
      both detection and analysis in hospital and during daily life conditions. Silent
      myocardial ischemia exhibits a circadian pattern. It represents an imbalance
      between myocardial oxygen supply and myocardial oxygen demand, and can be
      triggered by both physical and mental stress. The important role of endothelial
      dysfunction and autonomic nervous system influences has been recently elucidated.
      Up to 75% of ischemic episodes in patients are silent. Patients with asymptomatic
      coronary artery disease, chronic stable angina and unstable angina, and those
      postmyocardial infarction or postrevascularization who exhibit ST segment shift
      all show adverse short and long term prognosis compared with controls. Treatment
      modalities have included nitrates, beta-blockers, calcium antagonists,
      phosphodiesterase inhibitors, anxiolytics, anti-platelet agents and
      revascularization procedures. While the majority of these studies have
      demonstrated significant reduction in the frequency of silent myocardial
      ischemia, limited data on influencing prognosis are available; thus
      recommendations regarding treatment of these patients await the results of
      ongoing clinical trials.

PMID- 7728641
TI  - Changes in myocardial oxygen consumption and efficiency with heart failure
      therapy measured by 11C acetate PET.
AB  - The application of 11C acetate kinetics determined by positron emission
      tomography (PET) imaging has been proposed as a noninvasive means to measure
      myocardial oxygen consumption in order to determine myocardial efficiency. Such
      an approach considers the balance of the effect of ventricular performance and
      myocardial oxygen consumption (MVO2), which may be important in the assessment of
      heart failure but is not usually evaluated by current methods. In this paper, the
      authors review their previously published series of studies, in which the aim was
      to: first, apply the 11C acetate PET approach in patients with dilated
      cardiomyopathy in order to determine myocardial oxidative metabolism and estimate
      myocardial efficiency; second, verify a correlation between 11C acetate kinetics
      and directly measured MVO2; and third, evaluate the effects of dobutamine and
      nitroprusside on MVO2 and efficiency in dilated cardiomyopathy. In these previous
      studies, 13 patients with severe dilated cardiomyopathy were studied, via
      echocardiography, hemodynamic and PET studies, at baseline and during drug
      infusion. Seven patients were given dobutamine and six were given nitroprusside.
      A two-compartment kinetic model approach was applied to 11C time activity curves
      obtained from dynamic 11C acetate PET imaging to determine the clearance rate
      constant, k2. Myocardial efficiency was estimated from a work metabolic index,
      defined as (stroke work index multiplied by heart rate) divided by k2. The k2
      significantly increased with dobutamine (P < or = 0.05), consistent with
      increased MVO2, and tended to decrease with nitroprusside. The work metabolic
      index derived from hemodynamic parameters increased significantly with both drug
      regimens (P < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728642
TI  - The relationship of serum ferritin with sex and exercise in Canadians of
      Icelandic descent: implications for prevention of coronary artery disease.
AB  - OBJECTIVE: To investigate the relationship of serum ferritin with sex and
      exercise. DESIGN AND SETTING: A cross-sectional design study carried out in
      Winnipeg, Manitoba. SUBJECTS: Urban Canadians of Icelandic descent, aged 21 to 60
      years, took part in this investigation. Subjects were stratified by age, sex and
      menstrual status. INTERVENTIONS: Venous blood samples from fasting subjects were
      drawn for serum ferritin, hemoglobin and hematocrit analyses. Various
      anthropomorphic measurements were taken, and subjects underwent submaximal cycle
      ergometry testing. A health and lifestyles questionnaire and a four-day
      prospective food record were administered. MAIN RESULTS: Mean serum ferritin
      levels obtained were 187.93 and 47.84 micrograms/L for males and females,
      respectively. Mean serum ferritin levels were 33.06 micrograms/L and 71.14
      micrograms/L for premenopausal and postmenopausal females, respectively. The mean
      weekly consumption of alcohol was 190 mL/week and 80 mL/week for males and
      females, respectively. The mean dietary intake of iron was 27.3 and 18.9 mg/day
      for males and females, respectively. Males, but not females, who exercised 45
      mins or more per week had significantly lower levels of serum ferritin than their
      sedentary counterparts. In males, hemoglobin, hematocrit and the consumption of
      alcohol were positively correlated with serum ferritin, while exercise time was
      negatively correlated with serum ferritin. A trend towards lower serum ferritin
      levels at higher workloads was observed in males, but did not reach statistical
      significance. In females, age and dietary intake of iron were found to be
      positively correlated with serum ferritin, while history of anemia, menstrual
      status and workload were negatively correlated with serum ferritin. CONCLUSIONS:
      These findings suggest that regular aerobic exercise may decrease iron stores in
      the body. This may be clinically significant since high serum ferritin has been
      cited as a risk factor for coronary artery disease.

PMID- 7728643
TI  - Takayasu arteritis may be underdiagnosed in North America.
AB  - OBJECTIVES: To summarize some of the literature about Takayasu arteritis, a
      nonspecific chronic inflammatory disease involving the aorta and its main
      branches, and to analyze the criteria for its diagnosis. The pulmonary artery and
      its branches, as well as the coronary arteries, may also be involved. DATA
      ANALYSIS: Although Takayasu arteritis has been commonly reported in Asian
      countries such as Japan, India, China and Korea, case reports from other parts of
      the world describing symptoms of this disease are also available. Because of
      nonspecific pathology, a rather nonspecific initial clinical presentation and an
      obligatory criterion of age (40 years or younger) it is possible that the disease
      may be underdiagnosed in Europe and North America. The cause of this disease
      remains obscure. Various infections have been blamed but genetic and
      immunological disturbances seem to play a major role in bringing Takayasu
      arteritis into the list of autoimmune disease. INTERVENTIONS: Takayasu arteritis
      responds well to glucocorticoids/cyclophosphamide in the acute (prepulseless)
      phase. In the chronic fibrotic phase, treatment of hypertension and various
      angioplastic and surgical interventions are required. CONCLUSIONS: Adoption of
      improved diagnostic criteria may change the prevailing view that Takayasu
      arteritis is an Asian disease. Understanding of the pathogenesis at cellular and
      molecular levels is needed. Creation of an animal model would be a desirable tool
      in that direction.

PMID- 7728644
TI  - Experience of immediate stenting, perfusion balloon and secondary stenting in
      failed angioplasty.
AB  - OBJECTIVE: To present a comparative analysis of the immediate and short term
      experience of stent implantation as the initial treatment for failed angioplasty
      (immediate stenting) with the staged approach of prolonged inflation with a
      perfusion balloon followed by stent implantation if prolonged inflation was
      unsuccessful (secondary stenting). DESIGN: Retrospective analysis of the outcome
      of 90 consecutive patients from a single institution undergoing one of these
      treatment strategies for failed angioplasty. INTERVENTIONS AND MAIN RESULTS: The
      initial treatment for failed angioplasty was prolonged inflation with a perfusion
      balloon in 59 and immediate stent implantation in 31 patients. Angiographic
      success (less than 50% residual and normal flow) was achieved in 24 of 59 (41%)
      with the perfusion balloon (mean duration of inflation 12.2 +/- 8.3 mins) and in
      30 of 31 (97%) with immediate stent implantation (P = 0.0001). Of the 35 patients
      in whom the perfusion balloon was unsuccessful secondary stenting was attempted
      in 27, with angiographic success in 24 (89%). Stent thrombosis occurred in four
      (13%) of the immediate stent group and in three (13%) of the secondary stent
      group. Acute ischemia compatible with vessel occlusion occurred in one (4%) of
      the perfusion balloon alone group following an initially successful result. One
      month following the procedure, 23 (72%) of the patients treated with perfusion
      balloon alone, 26 (84%) of the immediate stent group and 21 (78%) of the
      secondary stent group had a successful outcome and were free from major
      complications. CONCLUSION: Immediate stent implantation and the staged approach
      of prolonged inflation with a perfusion balloon followed by secondary stent
      implantation if prolonged inflation was unsuccessful yielded similar results.

PMID- 7728645
TI  - Adenosine infusion: a rational approach towards induced hypotension.
AB  - OBJECTIVES: To examine the systolic (SBP) and diastolic (DBP) blood pressure
      (mmHg) and heart rate (beats/min) responses to varying doses and rates of
      adenosine administration in awake and anesthetized swine. DESIGN: Adult swine
      underwent sterile insertion of chronic carotid artery and jugular vein catheters.
      After recovery, baseline blood pressure and heart rate values were obtained.
      Three rates (mg/kg/min) of adenosine were infused in a randomized block design
      (low: 0.06 for 20 mins; medium: 0.12 for 10 mins; and high: 0.24 for 5 mins) to a
      total dose of 1.2 mg/kg. After 5 mins of infusion, three separate doses (0.3
      mg/kg; 0.6 mg/kg; and 1.2 mg/kg) were compared. RESULTS: In awake animals, only
      the highest dose significantly decreased (P < or = 0.0001) SBP by 21% and DBP by
      43% while increasing heart rate by 32%. At this high dose, the rate of
      administration was compared. Medium rates significantly decreased (P < or =
      0.0002) SPB by 18%, DBP by 33% and elevated heart rate by 27%. High rates caused
      even greater changes (SBP 21%, DBP 43%, heart rate 32%). The low rate did not
      alter SBP, DBP or heart rate. Anesthetized swine had a greater decrease in blood
      pressure, which was not accompanied by alterations in heart rate. CONCLUSIONS:
      This study clarifies that the blood pressure and heart rate effects of adenosine
      are both dose and rate dependent in awake and anesthetized swine. The dose
      dependent responses can be controlled by the rate of administration. Heart rate
      increased only in the awake state, while in the anesthetized state no alteration
      of heart rate was observed. The greater decline in SBP and DBP found in
      anesthetized swine was likely due to the absence of compensatory increases in
      heart rate as was observed in awake animals.

PMID- 7728646
TI  - Lyme carditis: indications for cardiac pacing.
AB  - Lyme disease is a tick-borne illness caused by the spirochete Borrelia
      burgdorferi. It is the most common reported vector-borne illness in the United
      States. The clinical course of Lyme disease is divided into early and late
      phases. Early disease may be limited or disseminated. Generally, cardiac
      complications occur in the early disseminated phase. Disturbance of
      atrioventricular conduction is the most commonly recognized cardiac manifestation
      of Lyme disease. This is usually self-limited and does not require permanent
      cardiac pacing. A case of Lyme carditis with atrioventricular block requiring
      permanent pacing is reported and the indications for cardiac pacing in this
      disease are reviewed.

PMID- 7728647
TI  - Report of a patient with syndrome X due to excessive adenosine effect: myocardial
      migraine without myocardial ischemia.
AB  - A 53-year-old female presented with disabling chest pain. The pain had most of
      the characteristics of ischemic pain; however, the results of the initial
      clinical investigation were consistent with the diagnosis of syndrome X. That is,
      her treadmill exercise test was positive but her coronary angiogram was normal. A
      dipyridamole-thallium test resulted in severe chest pain, marked ST
      abnormalities, but no evidence of any focal reduction in flow. A dipyridamole
      stress echocardiogram revealed that left ventricular function was entirely normal
      during the dipyridamole-induced pain and ST segment abnormalities, making
      ischemia an unlikely cause for either. To attempt to account for this paradox,
      the hypothesis was generated that both the pain and ST segment abnormalities were
      due to a primary abnormality of adenosine metabolism rather than secondary to
      ischemia. Accordingly, adenosine-MIBI scans were done with and without
      pretreatment with aminophylline. Infusion of adenosine virtually immediately
      resulted in crushing chest pain and profound ST abnormalities again without any
      evidence of focal abnormalities of MIBI estimated flow. By contrast,
      administration of adenosine after pretreatment with aminophylline failed to
      produce either chest pain or ST abnormalities. Moreover, long term therapy with
      aminophylline almost entirely relieved the symptoms which had been so
      distressing. This case indicates that there is a subset of patients with syndrome
      X--in which faults in adenosine metabolism result in excessive adenosine
      accumulation or effect and this results, in turn, in adenosine-induced ischemic
      like chest pain and adenosine-induced ST abnormalities. There is, however, no
      actual ischemia of the myocardium. Given the known effects of adenosine on
      coronary flow, the problem in this subset of patients appears to be equivalent to
      an attack of myocardial migraine and blockers of adenosine action might be of
      help to other patients with a similar pathophysiology for their chest pain.

PMID- 7728648
TI  - The rationale for nitrates in angina pectoris.
AB  - Organic nitrates are among the oldest drugs used in the management of patients
      with ischemic heart disease. The most frequently used nitrates are nitroglycerin,
      isosorbide dinitrate and isosorbide-5-mononitrate. Their duration of action can
      be influenced by choice of substance, frequency of administration, formulation
      (eg, extended release) and route of administration. As well as providing
      effective treatment of acute angina, nitrates produce a long term prophylactic
      effect. Stable plasma nitroglycerin levels lasting longer than 10 to 12 h are not
      desirable due to the rapid development of tolerance. Simple, well-designed dosing
      schedules can avoid tolerance and rebound phenomena and can improve patient
      compliance.

PMID- 7728649
TI  - The evolving role of calcium channel blockers in the treatment of angina
      pectoris: focus on felodipine.
AB  - Calcium channel blockers are used extensively in the treatment of the three major
      anginal syndromes. In the treatment of Prinzmetal's angina, their antivasospastic
      properties account for their therapeutic effectiveness. Calcium channel blockers
      are drugs of first choice in this syndrome. In chronic stable angina, calcium
      channel blockers may be used as monotherapy or in combination with beta-blockers
      and/or nitrates. In patients with unstable angina, reduction in the incidence of
      ischemic episodes produced by calcium channel blockers is well documented. Recent
      data suggest that calcium channel blockers should generally be used in
      combination with beta-blockers, nitrates and antithrombotic agents. Patients with
      ischemic heart disease often exhibit reduced ventricular function. All of the
      first generation calcium channel blockers exacerbate symptoms in patients with
      established heart failure and may precipitate heart failure, particularly when
      combined with beta-blockers. Second generation vascular-selective
      dihydropyridines have been introduced recently. Vascular selectivity determines
      the drug's degree of negative inotropic effect. Felodipine is one of the most
      vascular selective of the available dihydropyridines and has no negative
      inotropic effects at clinically administered doses. In a long term study,
      felodipine, 20 mg/day, abolished symptoms and chronic ischemic episodes in 81% of
      treated subjects with Prinzmetal's angina. In patients with stable angina,
      felodipine has been found to be effective either as monotherapy or in combination
      with beta-blockers. In patients with known or suspected ventricular dysfunction,
      vascular-selective dihydropyridines such as felodipine offer advantages over the
      nonselective calcium channel blockers, particularly in patients receiving beta
      blockers.

PMID- 7728650
TI  - Ischemic heart disease: bridging the gap between theory and practice.

PMID- 7728651
TI  - Nitrates in myocardial infarction: a current perspective.
AB  - In addition to well-established roles in the management of stable angina,
      unstable angina and heart failure, nitrates are widely used in the management of
      acute infarction and the subacute period of recovery after infarction. A meta
      analysis suggested that intravenous nitrate therapy in acute infarction reduced
      mortality by 35%. Subsequently, two recently reported 'mega' trials, GISSI-3 and
      ISIS-4, addressed the role of nitrates during and after infarction. The results
      of the mega trials have failed to substantiate a statistically significant
      benefit for nitrates. The contrast between the promising results of the meta
      analysis and the disappointing results of the mega trials raises a number of
      issues considered in this paper. The role of nitrates in acute myocardial
      infarction remains unclear. The mega trials do offer some suggestive evidence of
      an early benefit of nitrate therapy. If any benefit does exist, it must be much
      smaller than the 35% reduction in mortality suggested by the meta-analysis.
      Further trials are required to assess the possibility of an early acute benefit.
      Any benefits will probably apply only to subgroups of infarcts.

PMID- 7728652
TI  - Lytic infection of Escherichia coli biofilms by bacteriophage T4.
AB  - Escherichia coli 3000 XIII formed biofilms on the surface of polyvinylchloride
      coupons in a modified Robbins device. Bacteriophage T4D+ infected cells in the
      biofilm and replicated. It is commonly held that bacteriophage cannot infect
      surface-attached bacteria (biofilms) because such bacteria are protected by an
      exopolymeric matrix that binds macromolecules and prevents their diffusion into
      the biofilm. To our knowledge this is the first observation that a bacteriophage
      can infect and multiply within cells growing as a biofilm.

PMID- 7728653
TI  - Tryptophan 2,3-dioxygenase in Saccharomyces cerevisiae.
AB  - The tryptophan pyrrole-ring cleavage enzyme (TPCE) was detected in the yeast
      Saccharomyces cerevisiae. TPCE activity existed constitutively and was markedly
      induced by culturing the cells in a medium containing 0.1% (w/v) L-tryptophan. We
      purified partially the enzyme from the L-tryptophan-induced cells by phospho
      cellulose column chromatography. The partially purified enzyme was stimulated
      solely by L-ascorbic acid, a nonspecific reductant, suggesting that the yeast
      TPCE is not indoleamine 2,3-dioxygenase, but rather tryptophan 2,3-dioxygenase.
      The enzyme metabolized L-tryptophan preferentially, and D-tryptophan slightly.
      KCN and NaN3, exogenous ligands of heme, inhibited the enzyme activity
      drastically, indicating that yeast tryptophan 2,3-dioxygenase contains heme(s) in
      its active site. The optimal pH of the enzyme was 6.5. Upon two-dimensional
      polyacrylamide gel electrophoresis, a protein staining spot was identified that
      was induced by L-tryptophan and whose intensity changed in correlation with the
      tryptophan 2,3-dioxygenase activity after phospho-cellulose column
      chromatography. This protein, exhibiting a molecular weight of approximately
      38,000 and an isoelectric point of approximately pH 8.0, may be identified as a
      subunit of yeast tryptophan 2,3-dioxygenase.

PMID- 7728654
TI  - Nucleotide sequence and transcriptional analysis of the celD beta-glucanase gene
      from Ruminococcus flavefaciens FD-1.
AB  - The nucleotide sequence of the celD gene, which encodes endoglucanase and
      xylanase activity, from Ruminococcus flavefaciens FD-1 was determined. The DNA
      sequence of celD contains an open reading frame of 1215 nucleotides that encodes
      a polypeptide of 405 amino acids with a molecular mass of 44,631 Da. The primary
      amino acid sequence of CelD was screened against the GenBank data base for
      similar polypeptide sequences and the analysis indicated that CelD has common
      features with endoglucanases from the family E cellulases. Both hydrophobic
      cluster and BESTFIT (Genetics Computer Group (University of Wisconsin) package)
      analyses confirmed this relationship. Pairwise alignments using BESTFIT revealed
      that CelD was most closely related to endE4 from Thermomonospora fusca over a 160
      amino acid window. The histidine, aspartate, and glutamate residues identified as
      being essential for catalytic activity in family E cellulases are conserved in
      CelD. A Shine-Dalgarno-like sequence was present 5 base pairs (bp) upstream of
      the translation start site. Primer extension analysis indicated that different
      transcription initiation sites are used to initiate transcription of celD in
      Escherichia coli and R. flavefaciens. In the case of R. flavefaciens the
      transcription initiation site is at a T residue (nucleotide 273) 16 bp upstream
      from the translational start site. A region resembling a sigma 70-like-10
      promoter sequence is present upstream from the transcription initiation site but
      there is no apparent-35 region. In contrast, transcription in E. coli is
      initiated at a C residue 258 bp upstream from the translational start site and a
      sequence resembling a omega 70-like-10 region is present 5 bp upstream of this
      residue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728655
TI  - Taxonomy and protein fingerprinting of halophilic Vibrio isolates from bivalves
      of the Ebre delta.
AB  - A total of 380 isolates of halophilic Vibrio and related bacteria isolated from
      shellfish bred in the Ebro delta (in northeastern Spain) were studied by
      biochemical characterization; this allowed the use of numerical taxonomy
      programs. All but 25 isolates fell into 12 phenotypes. The analysis of whole-cell
      electrophoretic fingerprints of 100 isolates confirmed the numerical analysis of
      biochemical and morphological traits.

PMID- 7728656
TI  - Contact-dependent acquisition of transferrin-bound iron by two strains of
      Haemophilus parasuis.
AB  - Two strains of Haemophilus parasuis, namely, the type strain (ATCC 19417) and
      strain E751, were investigated with respect to iron acquisition. Both strains
      produced iron-repressible outer membrane proteins and could acquire iron from
      porcine transferrin but not from porcine lactoferrin. Neither strain used bovine
      transferrin, and human transferrin was used to only a very limited extent, if at
      all. In all cases, iron acquisition from transferrin required direct contact
      between the organisms and the protein. An affinity isolation technique based on
      biotinylated porcine transferrin plus streptavidin-agarose, followed by SDS-PAGE,
      allowed the isolation and identification of two potential porcine transferrin
      binding polypeptides (94 and 60 kDa) from total membranes derived from the type
      strain grown under iron-restricted conditions but only one (96 kDa) from strain
      E751. Each of these polypeptides was iron repressible and was not isolated when
      biotinylated human or bovine transferrin was used instead of biotinylated porcine
      transferrin. It is concluded that both strains acquire transferrin-bound iron by
      means of siderophore-independent mechanisms and that the isolated polypeptides
      represent porcine transferrin receptor components.

PMID- 7728657
TI  - Cloning the gene for the heat shock response positive regulator (sigma 32
      homolog) from Pseudomonas aeruginosa.
AB  - A 31 base pair synthetic oligonucleotide based on the genes for the Escherichia
      coli heat shock sigma factor (rpoH) and the Pseudomonas aeruginosa housekeeping
      sigma factor (rpoD) was employed in conjunction with the Tanaka et al. (K.
      Tanaka, T. Shiina, and H. Takahashi, 1988. Science (Washington, D.C.), 242: 1040
      1042) RpoD box probe to identify the location of the rpoH gene in P. aeruginosa
      genomic digests. This gene was cloned into plasmid pGEM3Z(f+), sequenced, and
      found to share 67% nucleotide identity and 77% amino acid homology with the rpoH
      gene and its product (sigma 32) of E. coli. The plasmid containing the rpoH gene
      complemented the function of sigma 32 in an E. coli rpoH deletion mutant.
      Furthermore, this plasmid directed the synthesis of a 32-kDa protein in an E.
      coli S-30 in vitro transcription-translation system. Primer extension studies
      were used to identify the transcriptional start sites under control and heat
      stressed (45 and 50 degrees C) conditions. Two promoter sites were identified
      having sequence homology to the E. coli sigma 70 and sigma 24 consensus
      sequences.

PMID- 7728658
TI  - Diagnosis of Clostridium difficile associated diarrhea: comparison of three rapid
      methods employing different markers for detection.
AB  - Latex agglutination and the enzyme immunoassays Cytoclone (EIA-C) and VIDAS (EIA
      V) were compared with a cytotoxicity assay for the diagnosis of Clostridium
      difficile associated diarrhea. Among patients with discrepant results, the
      cytotoxicity assay and clinical assessment were used to evaluate the performance
      of the latex agglutination and EIA tests. Clostridium difficile associated
      diarrhea was documented in 30/149 samples (20.1%) from 130 patients. All test
      results matched in 113 instances. Latex agglutination, EIA-C, and EIA-V yielded
      false positive results in 10, 4, and 7 samples and false negative results in 8,
      9, and 14 samples, respectively. Latex agglutination demonstrated 87.8%
      efficiency compared with 91.3% for EIA-C and 85.7% for EIA-V and 3 min hands-on
      time compared with 4.5 min for EIA-V and 10 min for EIA-C. On the basis of these
      findings and given the fact that all rapid tests have their shortcomings, we
      believe that latex agglutination is the most practical method.

PMID- 7728659
TI  - Neither reduced uptake nor increased efflux is encoded by tellurite resistance
      determinants expressed in Escherichia coli.
AB  - Rates of uptake of the TeO3(2-) oxyanion were investigated in Escherichia coli
      cells containing tellurite resistance determinants from both plasmid (RK2Ter,
      R478, pMER610, MIP233, pHH1508a, pMUR) and chromosomal (tehAB) sources. The
      uptake was investigated to determine whether or not reduced uptake or increased
      efflux is involved in the tellurite resistance mechanism. Reduced TeO3(2-) uptake
      generated by cultures harboring arsABC from the plasmid R773, which has been
      previously shown to be an oxyanion efflux transporter, was used as the standard.
      Uptake curves were found to be essentially identical among E. coli cultures
      harboring the tellurite resistance plasmids RK2Ter, pMER610, pHH1508a, and pMUR
      and cultures harboring tellurite-sensitive control plasmids. Cultures harboring
      clones of the tehAB operon from E. coli showed no change in the TeO3(2-)
      accumulation. Cultures harboring R478 demonstrated reduced uptake. However, a
      subclone containing only the tellurite resistance determinant displayed no
      reduced uptake. This suggests that there may be another determinant on R478 other
      than the primary tellurite resistance determinant that gives rise to TeO3(2-)
      efflux. These results demonstrate that neither reduced uptake nor increased
      efflux is responsible for the tellurite resistance in the resistance determinants
      investigated here.

PMID- 7728660
TI  - Defining wound infection in stoma closure.

PMID- 7728661
TI  - Management of contaminated wounds.

PMID- 7728662
TI  - The abnormal mammogram in clinically normal breasts: a challenge for surgeons.

PMID- 7728663
TI  - Diagnostic peritoneal lavage.

PMID- 7728664
TI  - Secondary hyperparathyroidism and renal osteodystrophy.

PMID- 7728665
TI  - Diagnostic peritoneal lavage versus abdominal computed tomography in blunt
      abdominal trauma: a review of prospective studies.
AB  - OBJECTIVE: To determine whether abdominal computed tomography (CT) or diagnostic
      peritoneal lavage (DPL) should be used in the evaluation of hemodynamically
      stable patients with blunt abdominal trauma and equivocal findings on physical
      examination. DATA SOURCE: MEDLINE. STUDY SELECTION: Prospective studies of
      hemodynamically stable trauma patients with blunt abdominal trauma and equivocal
      findings on physical examination that compared abdominal CT and DPL. DATA
      EXTRACTION: Data were extracted by a single observer. DATA SYNTHESIS: Most
      studies had excellent DPL results. The mean sensitivity was 98% (range from 90%
      to 100%), the mean specificity was 92% (range from 73% to 100%), the mean
      positive predictive value (PPV) was 82% (range from 57% to 92%), the mean
      negative predictive value (NPV) was 100% (range from 99% to 100%) and the mean
      accuracy was 93% (range from 80% to 98%). One study reported a low specificity
      (73%), PPV (57%) and accuracy (80%) for DPL, which may have been due to the loose
      criteria for red blood cells used in that study. The mean CT values were as
      follows: sensitivity 60% (range from 20% to 97%), specificity 98% (range from 91%
      to 100%), PPV 88% (range from 50% to 100%), NPV 84% (range from 76% to 93%) and
      accuracy 87% (range from 73% to 97%). In studies done in the mid-1980s the CT
      results were inferior, but they were improved in studies reported in the 1990s
      (sensitivity 88%, NPV 97%, accuracy 92%). These latest studies also suggest that
      CT and DPL are complementary rather than equivalent studies. CONCLUSION: DPL
      should be performed if there are no contraindications and no associated injuries
      that would be better delineated by CT, in which case abdominal CT is indicated.

PMID- 7728666
TI  - The community general surgeon: a time for renaissance.
AB  - The practice of general surgery in smaller Canadian communities requires a broad
      scope of training, and recently the Royal College of Physicians and Surgeons of
      Canada introduced training requirements to meet the needs of these communities.
      The traditional role of physicians and surgeons in relation to the hospital
      boards is changing, with the development of regional health boards. Surgeons must
      be adaptable to these changes while striving to preserve the standards of
      surgical care in the new environment. The 1990 Canadian Medical Association
      manpower studies indicated that there will soon be a major shortage of general
      surgeons in Canada. In 1990, 48% of general surgeons in Canada were over 55 years
      of age. In communities with a population of 10,000 or less, there were relatively
      more general surgeons than other specialists, but, again, they were
      proportionately older. Recruitment to general surgery is a concern. A survey of
      205 residents obtaining the Royal College fellowship in surgery between 1991 and
      1993 revealed that 107 took post-fellowship training; of these, 46 developed
      academic careers, 17 became community surgeons and 44 were lost to surgical
      practice (they went into cardiac surgery or emigrated). Ninety-eight did not take
      further training; of these, 5 developed academic careers, 87 chose community
      practice and 6 emigrated. The role of the general practitioner in providing
      surgical services in remote areas was the topic of discussion between the
      Canadian Association of General Surgeons (CAGS), the Royal College and the
      College of Family Physicians of Canada. Guidelines were developed and approved by
      the CAGS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728667
TI  - From premise to principle: the impact of the gut hypothesis on the practice of
      critical care surgery.
AB  - Clinical decision making is ideally founded on evidence of efficacy derived from
      well-designed randomized clinical trials. In reality, such evidence is rarely
      available to the surgeon caring for the patient with multiple trauma or who is
      critically ill, and complex management decisions must be made by less rigorous,
      more subjective means. An understanding of the normal biologic state and its
      alterations during disease has long been a fundamental component of medical
      education. Although such an understanding does not provide practitioners with
      grounds for assuming therapeutic efficacy in a particular patient, it does shape
      their perception of the important principles that guide the decision-making
      process. In contrast to evidence-based medicine--the making of therapeutic
      decisions through the systematic synthesis of results of clinical trials--a
      knowledge of pathobiology supports a complementary approach that the authors term
      "inference-based medicine"--the use of insights from studies in basic biology to
      establish principles that guide the practitioners' approach to groups of
      patients. The impact of a relatively new area of biologic investigation into the
      effects of the gut flora on systemic homeostasis, and the perturbations of this
      process in trauma and critical illness are reviewed. Re-emergence of the "gut
      hypothesis" has had a relatively modest effect if measured by the introduction of
      promising new forms of specific therapy. However, these investigations have
      resulted in a fundamental paradigm shift in two important areas in the practice
      of trauma and critical care surgery: the use of antimicrobial agents and the
      route of nutritional support.

PMID- 7728668
TI  - Stoma closure and wound infection: an evaluation of risk factors.
AB  - OBJECTIVE: To assess the infection rate in the nonstoma wound in patients who
      undergo stoma closure. DESIGN: Chart review. SETTING: A tertiary-care hospital.
      PATIENTS: Ninety-five patients who underwent elective closure of an abdominal
      wall stoma requiring a separate abdominal incision. INTERVENTIONS: Elective
      general surgery procedures. MAIN OUTCOME MEASURE: Wound infection rate. RESULTS:
      The overall wound infection rate was 29%. Primary wound closure was associated
      with a markedly increased wound infection rate (41%) compared with delayed
      primary or secondary wound closure (15%). No other preoperative factor
      specifically predicted a high rate of postoperative nonstoma wound infection.
      CONCLUSIONS: The nonstoma wound during elective closure of an abdominal stoma is
      at high risk for infection postoperatively. Delayed primary or secondary closure
      may lessen this risk.

PMID- 7728669
TI  - The effect of surgical wound infection on postoperative hospital stay.
AB  - OBJECTIVE: To determine the effect of surgical wound infection on postoperative
      duration of hospital stay. DESIGN: A case-control study nested within a cohort.
      SETTING: A tertiary-care hospital. PATIENTS: Selected from a cohort of 4702
      inpatients who underwent surgical procedures over a 12-month period. There were
      3602 patients, 1100 having been excluded because of lack of infection associated
      with a particular surgical procedure, because of "lumping" of procedures under a
      nonhomogeneous heading or because a procedure was unlikely to be the reason for
      the patient's hospitalization. MAIN OUTCOME MEASURE: Postoperative duration of
      hospital stay. RESULTS: In the cohort 89 wound infections were identified, 73 of
      these occurring with procedures selected for study. Five patients were excluded
      from the study because of data deficiencies, leaving 68 patients who underwent 15
      different procedures. These were compared with 136 control patients selected by
      stratified random sample from a list of patients who underwent the same risk
      indexed procedure in the same surgical division. Wound infection patients and
      controls did not differ in anesthetic risk score or procedure duration. Patients
      with infection remained in hospital 19.5 days longer than controls (95%
      confidence interval, range from 11.0 to 27.9 days). Deep-seated infections
      prolonged the hospital stay more than superficial incisional infections (24.3
      versus 13.2 days). CONCLUSIONS: Surgical wound infection markedly prolonged the
      duration of hospitalization in the University of Alberta Hospitals, longer than
      that documented in previous studies in other countries. Maximizing opportunities
      to prevent wound infection would be beneficial to both patients and hospitals.

PMID- 7728670
TI  - Transfusion practice in support of surgery during introduction of a hospital
      based autologous presurgical blood donor program.
AB  - OBJECTIVES: To assess blood use in support of elective surgery during the
      introduction of a hospital-based presurgical autologous blood donor program and
      to identify changes in transfusion practice. DESIGN: Case series over a 3-year
      period. SETTING: A tertiary-care, university-affiliated hospital. PATIENTS: All
      patients (887) who underwent, electively, one of four major surgical procedures
      between Apr. 1, 1990, and Mar. 31, 1993, during introduction of the hospital's
      autologous blood transfusion program. The criteria for donation were wide.
      INTERVENTIONS: Hip and knee arthroplasty, radical hysterectomy and radical
      prostatectomy. MAIN OUTCOME MEASURES: Increase or decrease in the use of
      autologous or allogeneic blood for transfusion for the four surgical procedures
      over the study period. RESULTS: For hip arthroplasty, the use of blood decreased
      significantly overall. The use of blood in support of radical hysterectomy and
      prostatectomy decreased but not significantly. In knee arthroplasty, blood use
      increased for reasons still under investigation. The contribution of autologous
      blood for the four procedures increased over the 3 years of the study from 17% to
      55%, and constituted 3.8% of red cell and whole blood transfusions. Avoidance of
      allogeneic transfusion in the 3rd year of the study was 64% for patients who
      underwent hip arthroplasty, 71% for those who underwent radical prostatectomy and
      77% for those who underwent knee arthroplasty and radical hysterectomy.
      CONCLUSIONS: Hospital-based autologous blood collection with wide eligibility
      criteria can contribute significantly to the availability of blood for elective
      surgery and can prevent allogeneic blood exposure in about 75% of patients who
      undergo, electively, one of four common procedures. Compared with other centres,
      there is room for further reduction in allogeneic blood exposure.

PMID- 7728671
TI  - The role of extracorporeal shock-wave lithotripsy in the treatment of symptomatic
      cholelithiasis.
AB  - OBJECTIVES: To determine the effectiveness of extracorporeal shock-wave
      lithotripsy (ESWL) and adjuvant bile-salt therapy for the treatment of
      symptomatic cholelithiasis. DESIGN: A prospective case study. Follow-up ranged
      from 3 to 54 months. SETTING: A university teaching hospital. PATIENTS: Two
      hundred and twenty-three patients with symptomatic cholelithiasis, a gallbladder
      that opacified at oral cholecystography and three or fewer radiolucent stones
      with a maximum total dimension of 3 cm. Of these patients, 197 were given bile
      salts (ursodeoxycholic acid or chenodeoxycholic acid, 8 to 10 mg/kg daily) and
      underwent ESWL. Twenty-eight were excluded because of noncompliance with the
      protocol or treatment failure before termination of the ESWL procedure.
      INTERVENTION: ESWL with a piezoelectric lithotripter. MAIN OUTCOME MEASURES: The
      success rate of the intervention, the causes of failure, associated complications
      and the recurrence rate of cholelithiasis. RESULTS: Of the 197 patients who
      underwent ESWL, 85 (43%) were free of stones after treatment. Treatment failure
      was caused by the following: unsatisfactory fragmentation (9%), increase in
      fragment size during bile-salt therapy (8%), severe diarrhea due to bile salts
      (3%), nonvisualization of fragments after the first ESWL (3%), acute
      cholecystitis (2%), persistence of small fragments at the end of the treatment
      protocol (2%) and acute pancreatitis (0.5%). Complications included biliary colic
      (21%), diarrhea (15%), acute cholecystitis (2.5%), acute pancreatitis (2%),
      macroscopic hematuria (2%), perirenal hematoma (0.5%) and vagal shock (0.5%). The
      recurrence rate was 18%. Causes of noncompliance with treatment (26%) were the
      length of treatment, the occurrence of biliary colic during this period and the
      high cost of bile salts. CONCLUSION: ESWL with bile salts as treatment for
      symptomatic cholelithiasis is not recommended for routine use.

PMID- 7728672
TI  - The abnormal mammogram in women with clinically normal breasts.
AB  - OBJECTIVES: To assess the impact of unnecessary referrals to breast surgeons as a
      result of abnormal mammograms in women with clinically normal breasts and to
      determine measures to make the management of such women more efficient. DESIGN: A
      case study. SETTING: A breast clinic in a university-affiliated hospital.
      PATIENTS: From among 6477 women referred for surgical breast assessment, 475 with
      asymptomatic, clinically normal breasts were referred solely on the basis of an
      abnormal mammogram. INTERVENTIONS: Mammography and breast biopsy. MAIN OUTCOME
      MEASURES: Need for surgical assessment as a result of mammographic findings,
      number of biopsies and the diagnosis of cancer. RESULTS: Clinically a breast
      abnormality was evident in 63 (13%) women and a malignant lesion in 14 of them
      (2.9% of the total). Of the 412 women who were confirmed as having clinically
      normal breasts, only 139 (33.7%) had mammograms originally reported as suspicious
      for cancer. After the mammograms were reviewed, 79% of women with such a
      suspicious mammogram underwent mammographic localization and biopsy: a malignant
      lesion was confirmed in 36.4% of these. Of the 475 women referred for assessment,
      only 202 (42.5%) had a significant clinical or mammographic abnormality. Of the
      412 women with clinically normal breasts only 110 (26.7%) required a biopsy and
      only 40 (9.7%) had cancer. CONCLUSIONS: Most women referred because of an
      abnormal mammogram have no significant problem or have one that can be resolved
      without surgical referral. Screening efficiency can be improved, patient anxiety
      controlled and cost controlled by a number of recommended measures.

PMID- 7728673
TI  - Fine-wire localization for nonpalpable mammographic abnormalities.
AB  - OBJECTIVE: To determine the predictive value of fine-wire localization (FWL)
      biopsy. DESIGN: A chart review. SETTING: The Royal Columbian Hospital, New
      Westminster, BC. PATIENTS: Two hundred and thirty-five women who underwent 239
      biopsies for abnormal mammographic findings between Jan. 1, 1991, and Dec. 31,
      1992. The average age was 58 years (range from 33 to 83 years). INTERVENTION: FWL
      biopsy. MAIN OUTCOME MEASURE: Positive findings of cancer on FWL biopsy. RESULTS:
      Mammographic findings were as follows: a mass only in 98 cases (41.0%),
      microcalcification in 90 (37.7%), a spiculated mass in 20 (7.5%), an ill-defined
      density in 18 (8.4%) and a mass with microcalcification in 13 (5.4%). Malignant
      lesions were found in 97 (40.6%) of 239 biopsies. These included 55 infiltrating
      ductal carcinomas, 31 in-situ carcinomas, 7 infiltrating lobular carcinomas and 4
      miscellaneous carcinomas. Spiculated masses were associated with malignancy in 18
      (90%) of the 20 biopsies. Also, 41 (42%) of the 98 masses and 30 (33%) of the 90
      microcalcifications were malignant. Only 4 (31%) of the 13 masses with associated
      microcalcification and 4 (22%) of the 18 ill-defined densities were malignant.
      CONCLUSION: The 40.6% rate of positive findings supports the use of FWL biopsy as
      a valuable tool in the diagnosis of nonpalpable breast cancers.

PMID- 7728674
TI  - Laparoscopic appendectomy versus open appendectomy: retrospective assessment of
      200 patients.
AB  - OBJECTIVE: To compare laparoscopic appendectomy (LA) with traditional methods as
      the primary treatment for acute appendicitis. DESIGN: A retrospective case
      series. SETTING: A regional, nonuniversity hospital in northwestern Quebec.
      PATIENTS: Two hundred patients with a clinical diagnosis of acute appendicitis:
      100 (43 men, 57 women; mean age 27 years) underwent laparoscopic appendectomy and
      100 (67 men, 33 women; mean age 21 years) had an open appendectomy (OA).
      INTERVENTIONS: LA or OA. MAIN OUTCOME MEASURES: Operating time, rate of
      conversion to OA, need for analgesia, morbidity and outcome. RESULTS: LA was
      successful in 88% of patients. The mean operating time was 50 minutes for LA
      versus 24 minutes for OA. On average, patients of the LA group had a 1-day
      decrease in postoperative hospital stay (2.6 versus 3.6 days). The wound
      infection rate was lower in the LA group (2% versus 12%) as was the intra
      abdominal abscess rate (2% versus 6.0%). There were no deaths in either group.
      The overall morbidity was 4.5% for the LA group and 18% for the OA group. A clear
      tendency toward a shorter convalescence was seen in the LA group. CONCLUSIONS: LA
      is a safe and viable treatment alternative for acute appendicitis. Prospective
      randomized studies are needed to confirm its potential advantages.

PMID- 7728675
TI  - The contributions of Alexis Carrel to the management of contaminated wounds.
AB  - Wound care through the ages has ranged from good to bad, and at times has been
      disgusting, with little scientific approach. von Eiselsberg's dictum of no touch
      for military wounds proved disastrous to patients with gunshot and shrapnel
      wounds in the First World War. Alexis Carrel, a brilliant experimental surgeon,
      spearheaded the research that led to the development and application of
      debridement and irrigation for combat wounds. Early in his career, Carrel
      reported on a miraculous cure that he had observed in Lourdes, France. However,
      this report resulted in a strained professional environment in his homeland of
      France, which persisted in spite of his subsequent moves to Canada and then to
      the United States. There he was awarded the Nobel Prize for Physiology and
      Medicine.

PMID- 7728676
TI  - Venous gangrene of the limbs.

PMID- 7728677
TI  - Wound infection during stoma closure.

PMID- 7728678
TI  - Abortion: legal, but right or wrong?

PMID- 7728679
TI  - Abortion: a violent procedure?

PMID- 7728680
TI  - Treatment of carpal tunnel syndrome.

PMID- 7728681
TI  - Treatment of carpal tunnel syndrome.

PMID- 7728682
TI  - Family-medicine centres caught in funding crunch.

PMID- 7728683
TI  - Folic acid and neural tube defects.

PMID- 7728684
TI  - Determining risk of surgical-site infections.

PMID- 7728685
TI  - Determining risk of surgical-site infections.

PMID- 7728686
TI  - Physician supply in Ontario: further observations on SHARP and the SHARP
      projections.
AB  - In this issue (see pages 1395 to 1398) Eva Ryten questions the validity of the
      data that supported the projection of a surplus of physicians in Ontario over the
      next two decades, as presented in an earlier article in CMAJ by Denton, Gafni and
      Spencer. The authors maintain that the data they used were appropriate. Although
      the average annual growth rate for the early 1990s calculated from Ontario Health
      Insurance Plan (OHIP) billing data is somewhat lower than the rate they projected
      for the decade as a whole, the OHIP-based rate is much closer to their figure
      than Ryten's rate. They also disagree with Ryten in their belief that the recent
      reduction of medical school enrollment will have a negligible effect on the
      physician population by the year 2000. They argue too that Ryten misunderstands
      the nature of the imbalance they project between the availability of intern and
      resident services and the requirements for those services. Finally, the authors
      note that there is an argument for setting requirements for practising physicians
      at levels lower than they had assumed. For that reason, even if the supply of
      practising physicians were to grow less rapidly than projected, a substantial
      surplus could still result by the year 2000.

PMID- 7728687
TI  - Physician-workforce and educational planning in Canada: has the pendulum swung
      too far?
AB  - Since the early '80s, and especially since the publication in 1991 of Toward
      Integrated Medical Resource Policies for Canada (the Barer-Stoddart Report),
      received wisdom has been that there is an oversupply of physicians in Canada and
      that medical school enrollment should be cut. In a CMAJ article published July 1,
      1994, that described a computer program to forecast the supply and demand of
      health care resources, Denton, Gafni and Spencer projected a substantial
      physician surplus in Ontario in the years 2000 and 2010, despite substantial cuts
      in Ontario medical school enrollment. The author questions the data used in the
      forecasts and reaches different conclusions. She advances an alternative
      hypothesis that current medical school admission levels are, in fact, too low.

PMID- 7728688
TI  - Defining basic services and de-insuring the rest: the wrong diagnosis and the
      wrong prescription.
AB  - The Canada Health Act of 1984 requires the provinces to cover all "medically
      necessary" services in order to be eligible for full federal contributions.
      However, neither the federal government nor any province has operationally
      defined the term "medically necessary service." As a result, coverage of certain
      medical services across the country is uneven. There is even greater variation in
      the coverage of nonmedical services (such as drugs and home care) that are not
      included in federal legislation. Recently, several provincial medical
      associations, with their respective provincial governments, have agreed to define
      and cover basic services and to de-insure services not found to be "medically
      necessary." The author argues that this process makes the wrong diagnosis of the
      cause of the woes of our health care system and then issues the wrong
      prescription. It also distracts decision makers from more worthwhile policies to
      reform the health care system.

PMID- 7728689
TI  - Core and comprehensive health care services: 3. Ethical issues.
AB  - The CMA's Working Group on Core and Comprehensive Health Care Services recognizes
      ethics to be one of the three key factors in determining which services should be
      publicly funded. The role of ethics is to identify and make explicit the
      principles and values, at individual and societal levels, that lie behind
      judgements and positions. Two types of ethical issues are addressed: one deals
      with the criteria for these services and the other with the process to be
      followed. The five ethical criteria discussed are fairness, age, lifestyle, the
      identifiable versus the statistical patient, and futility. An ethical process
      incorporates appropriate roles for the public physicians and payers (government)
      and accountability of all participants. A provided checklist for determining a
      fair process asks such questions as Do potential users of a service, its
      providers and the public have an adequate say in the decision about whether the
      service should be publicly funded? Are the reasons for the decision communicated
      to those affected by it? and is the service being denied to potential users on
      the basis of unfair discrimination or lifestyle?

PMID- 7728690
TI  - Guidelines for the use of allergen immunotherapy. Canadian Society of Allergy and
      Clinical Immunology.
AB  - OBJECTIVES: To recommend guidelines for the use of allergen immunotherapy to
      treat allergies in patients for whom allergen avoidance and drug therapy have not
      been sufficiently effective. OPTIONS: High-dose or low-dose allergen
      immunotherapy for the treatment of IgE-mediated allergy to insect stings,
      allergic rhinoconjunctivitis and asthma. OUTCOMES: Clinical evaluation of
      symptoms, objective measurement of reactions to nasal or bronchial allergen
      challenge, immunologic changes as a result of allergen immunotherapy and, among
      patients with anaphylactic reactions to stinging insects, clinical outcome of
      intentional sting challenge. EVIDENCE: A search of MEDLINE was conducted to
      identify articles that presented results of allergen immunotherapy. Proceedings
      of symposia held by international subcommittees and of consensus meetings, as
      well as references obtained from these sources, were reviewed. The articles were
      grouped according to their main subject: immunologic effects, specific allergies,
      the results of randomized placebo-controlled clinical trials, types of allergen
      extract and protocols for allergen immunotherapy, adverse effects and
      deficiencies of allergen immunotherapy. VALUES: Each member of the working group
      assessed the importance of such issues as basic immunologic effects, clinical
      efficacy, adverse effects and inappropriate use; the working group then arrived
      at a consensus. BENEFITS, HARMS AND COSTS: Implementation of these guidelines
      would lead to the appropriate use of allergen immunotherapy and control
      inappropriate treatment, which could result in adverse effects and increased
      costs of services for patients with allergies. RECOMMENDATIONS: Allergen
      immunotherapy with specific, standardized allergenic materials, administered in
      high-dose schedules, is effective in patients with an allergy to insect stings or
      allergic rhinoconjunctivitis, and in some patients with asthma, who have been
      correctly diagnosed through a meticulous history corroborated by positive results
      of skin tests and for whom avoidance of the allergen and drug therapy are not
      sufficiently effective. VALIDATION: These guidelines are similar to others being
      developed in the United States and recommended by the Joint Council of Allergy
      and Immunology and the American Academy of Allergy, Asthma and Immunology.
      SPONSOR: These guidelines were developed by a working group of the Canadian
      Society of Allergy and Clinical Immunology; no funding was received from any
      other source.

PMID- 7728691
TI  - Effective physician-patient communication and health outcomes: a review.
AB  - OBJECTIVE: To ascertain whether the quality of physician-patient communication
      makes a significant difference to patient health outcomes. DATA SOURCES: The
      MEDLINE database was searched for articles published from 1983 to 1993 using
      "physician-patient relations" as the primary medical subject heading. Several
      bibliographies and conference proceedings were also reviewed. STUDY SELECTION:
      Randomized controlled trials (RCTs) and analytic studies of physician-patient
      communication in which patient health was an outcome variable. DATA EXTRACTION:
      The following information was recorded about each study: sample size, patient
      characteristics, clinical setting, elements of communication assessed, patient
      outcomes measured, and direction and significance of any association found
      between aspects of communication and patient outcomes. DATA SYNTHESIS: Of the 21
      studies that met the final criteria for review, 16 reported positive results, 4
      reported negative (i.e., nonsignificant) results, and 1 was inconclusive. The
      quality of communication both in the history-taking segment of the visit and
      during discussion of the management plan was found to influence patient health
      outcomes. The outcomes affected were, in descending order of frequency, emotional
      health, symptom resolution, function, physiologic measures (i.e., blood pressure
      and blood sugar level) and pain control. CONCLUSIONS: Most of the studies
      reviewed demonstrated a correlation between effective physician-patient
      communication and improved patient health outcomes. The components of effective
      communication identified by these studies can be used as the basis both for
      curriculum development in medical education and for patient education programs.
      Future research should focus on evaluating such educational programs.

PMID- 7728692
TI  - Quality assessment of a discharge summary system.
AB  - OBJECTIVE: To assess the completeness of hospital discharge summaries and the
      efficiency of the discharge summary system in two urban teaching hospitals.
      DESIGN: Descriptive study, with follow-up telephone survey. SETTING: General
      internal medicine services at two urban tertiary care hospitals affiliated with
      the University of Ottawa. PATIENTS: A total of 135 patient charts, representing
      10% of the patients discharged from the services between Aug. 1 and Dec. 31,
      1993. Three charts were unavailable for review, and 26 were excluded because of
      patient death, early patient discharge (within 48 hours after admission) or lack
      of discharge summary; this left 106 summaries for analysis of completeness and
      114 (including the charts without a summary) for analysis of efficiency. OUTCOME
      MEASURES: Completeness: proportion of summaries in which the following
      information was reported: admission diagnosis, drug allergies, physical
      examination, significant laboratory tests and results, discharge diagnosis,
      discharge medications and medical follow-up. Efficiency: time taken to generate
      the discharge summary and whether the patient's family physician received it.
      RESULTS: Of the 106 charts with a discharge summary, information was available
      from the dictation system database for all but one (99.1% complete). Information
      was missing on the admission diagnosis in 34.0% (36/106) of the summaries, the
      discharge diagnosis in 25.5% (27/106) and the discharge medications in 22.8%
      (23/101). Of the 268 significant laboratory tests and results noted in the charts
      115 (42.9%) were not reported in the discharge summary. Of the 94 discharge
      summaries in charts with the patient's family physician listed on the facesheet,
      38 (40.4%) were not received by the family physician. CONCLUSIONS: Considerable
      deficiencies in the completeness of the discharge summaries and the efficiency of
      the discharge summary system were found in the participating hospitals.
      Replication of this study in other settings is indicated, and strategies to
      improve the process should be pursued.

PMID- 7728693
TI  - Cost-effectiveness of induction of labour versus serial antenatal monitoring in
      the Canadian Multicentre Postterm Pregnancy Trial.
AB  - OBJECTIVE: To determine the cost-effectiveness of induction of labour versus
      serial fetal monitoring while awaiting spontaneous labour in postterm
      pregnancies. DESIGN: Cost-effectiveness and cost-minimization analyses conducted
      as part of a Canadian multicentre randomized clinical trial. SETTING: Twenty-two
      Canadian hospitals, of which 19 were teaching hospitals and 3 were community
      hospitals. PATIENTS: Women with uncomplicated pregnancies of 41 or more weeks'
      gestation were randomly assigned to induction of labour or serial antenatal
      monitoring. Of the 3418 women enrolled, no data were received on 11. Therefore,
      results were based on data from 1701 women in the induction arm of the study and
      1706 women in the monitoring arm. MAIN OUTCOME MEASURES: Perinatal mortality and
      neonatal morbidity, rates of cesarean section and health care costs. Hospital
      costing models were developed specifically for the study. Data on use of major
      resources (e.g., length of hospital stay, surgical procedures, major diagnostic
      tests and procedures, and medications) for all trial participants were collected
      and combined with data on minor tests and procedures (e.g., laboratory tests)
      abstracted from a detailed review of medical records of a sample of patients.
      RESULTS: Because the results of the clinical trial showed a nonsignificant
      difference in perinatal mortality and neonatal morbidity between the induction
      and monitoring arms, the authors conducted a cost-minimization rather than a cost
      effectiveness analysis. The mean cost per patient with a postterm pregnancy
      managed through monitoring was $3132 (95% confidence interval [CI] $3090 to
      $3174) and per patient who underwent induction of labour was $2939 (95% CI $2898
      to $2981), for a difference of $193. The significantly higher (p < 0.0001) mean
      cost per patient in the monitoring arm was due mainly to the costs of additional
      monitoring and the significantly higher rates of cesarean section among these
      patients. Estimated conservatively, the savings resulting from a universal policy
      of managing postterm pregnancies by induction of labour in Canada may be as high
      as $8 million a year. CONCLUSIONS: A policy of managing postterm pregnancy
      through induction of labour not only results in more favourable outcomes than a
      monitoring strategy but does so at a lower cost.

PMID- 7728694
TI  - Age, physical trauma and care.
AB  - To cast light on the effects of aging on the metabolic responses to physical
      trauma an Ottawa researcher has studied strength and blood glucose metabolism in
      elderly people. He finds that because older people have less lean body mass,
      particularly muscle mass, than younger people, they are less able to tolerate
      trauma. They weaken faster and to a greater extent than younger patients who have
      experienced similar trauma, and they recover more slowly. At the same time,
      elderly people are less able to tolerate glucose, which is often given as part of
      their nutritional support. These findings have implications for care: the elderly
      trauma patient will be weaker than a younger counterpart, and nutrition will need
      to be provided early, with the glucose intolerance of elderly people borne in
      mind.

PMID- 7728695
TI  - Uniform requirements for manuscripts submitted to biomedical journals.
      International Committee of Medical Journal Editors.

PMID- 7728696
TI  - When the guns fell silent.

PMID- 7728697
TI  - Manitoba targets patient overuse as it tackles abuse of health care system.
AB  - Manitoba has begun to respond to overuse of its health care system by forcing
      people who visit too many doctors or pharmacies to limit their use to one doctor
      and one drugstore. The province reviewed the records of patients who made more
      than 67 office visits in a year and/or saw more than 12 physicians annually. The
      heaviest user made 247 office visits to 71 different physicians in 1 year. The
      new restriction applies to about 28 patients. The move is expected to save the
      province $116,000.

PMID- 7728698
TI  - Advent of mail-order pharmacy causes concern among some pharmacists.
AB  - MEDITrust, a major mail-order pharmacy, promises low drug prices and dispensing
      fees for people who order drugs via mail. Its arrival has created some strong
      opposition in Quebec. The Canadian Pharmaceutical Association says the arrival of
      mail-order companies may give community pharmacists an opportunity to promote the
      benefits of face-to-face contact with pharmacists. The CMA's Dr. Anne Carter says
      there will always be a need for community pharmacists, who can provide drugs on
      short notice and provide personal counselling for patients.

PMID- 7728699
TI  - Failure to pursue indications of spousal abuse could lead to tragedy, physicians
      warned.
AB  - Many women who are victims of battered-spouse syndrome are unable to disclose
      their abuse, yet cannot leave the relationship either. This frustrates health
      care professionals who want to help them and can lead to tragedy, as it did in
      the case of an Alberta woman who was recently acquitted of murder after using a
      battered-woman defence. The psychiatrist who testified at her trial says the
      challenge for physicians is to be alert for patients who may be victims of
      battery, and to try to encourage the confidence and self-esteem they need to
      break free from violently abusive relationships.

PMID- 7728700
TI  - Disabilities give some physicians a fresh insight into their profession.
AB  - Most physicians see disabilities only in the patients they treat, but some
      doctors speak from personal experience when they say disabilities should not be a
      barrier to practising medicine. Neurologist Gordon Robinson of Vancouver says the
      spinal problems that left him a paraplegic could not stop him from practising.
      Many aspects of his work didn't really require the use of his legs. He could
      still see patients in the office much as he had before simply by using an
      examining table that could be lowered. However, it may be more difficult
      convincing colleagues that physical disabilities are not an insurmountable
      barrier.

PMID- 7728701
TI  - Informed consent by children: the new reality.
AB  - Recent legislative changes in British Columbia and New Brunswick allow children
      to make their own decisions about health care, something that used to be the
      prerogative of their parents. In this article, Eike-Henner Kluge argues that the
      changes hold profound implications for physicians. He says they increase the
      responsibility placed on doctors, who must now consider whether a child is indeed
      competent, and whether the decision made by a competent child is indeed in the
      child's best interests.

PMID- 7728702
TI  - Family physicians can play important role helping women overcome drinking
      problems.
AB  - When alcoholic women seek medical assistance, it is more likely to be because of
      distress over interpersonal or family problems, and their complaints of anxiety,
      depression and insomnia will be treated with prescription drugs. The alcoholism,
      which presents differently in women than men, is often left undiagnosed and
      untreated. However, even when women seek help for a drinking problem, traditional
      and male-dominated support groups may not meet their unique needs. When it comes
      to alcoholism, men and women are certainly not created equal.

PMID- 7728703
TI  - Medicare "Canada's postwar miracle," US management expert tells CMA conference.
AB  - The diagnosis that Canadian medicare is a fundamentally troubled and gravely
      threatened system is quite distorted, says a professor of public policy and
      management at the Yale School of Management. Dr. Theodore Marmor praised medicare
      as "Canada's postwar miracle" during the CMA's 7th Annual Leadership Conference.

PMID- 7728704
TI  - Create culture of integrity to defeat research fraud, funding agencies say.
AB  - Widely reported cases of research fraud have eroded public confidence in
      scientific research. When funding agencies met last fall they underscored the
      importance of integrity in the research process and discussed steps that could be
      taken to promote it.

PMID- 7728705
TI  - Australia hopes new strategy will improve health services for aboriginal
      population.
AB  - Australia has embarked on a National Aboriginal Health Strategy that aims to give
      aboriginals equal access to health services by 2001. Although the harmful effects
      of colonization are now recognized, it is not possible to eradicate overnight the
      health problems resulting from 200 years of mistreatment and neglect, officials
      say. In implementing the strategy, the Australian government is spending $1.3
      billion over 5 years to improve the basic infrastructure of housing, water, waste
      disposal, roads and communications in aboriginal communities, enhance health
      services and encourage more aboriginals to seek careers in health care.

PMID- 7728706
TI  - American cigarettes have become a status symbol in smoke-saturated China.
AB  - Antismoking advocates often complain about smoking levels in Canada but our
      problems pale beside those of China, where it is estimated that 300 million
      people already smoke and more are being encouraged to do so by Western
      advertising. To its credit, the Chinese government is taking steps to discourage
      smoking as it prepares to host the 10th World Conference on Tobacco and Health in
      1997. By 2025, smoking-related disease is expected to kill 2 million Chinese a
      year.

PMID- 7728707
TI  - Cod-liver oil, vitamin D and the fight against rickets.
AB  - Although rickets has all but disappeared as a medical problem, the disease caused
      serious concern in turn-of-the-century England, where it reached epidemic
      proportions. The connection between rickets and a lack of vitamin D wasn't made
      until shortly after World War I, when it was determined that regular exposure to
      sunlight would eliminate the problem; another solution was to provide vitamin D
      supplements in milk. The problem hasn't disappeared entirely, however. Seventeen
      cases of rickets have been diagnosed at Toronto's Hospital for Sick Children in
      the past 5 years.

PMID- 7728708
TI  - The career paths of MHSc graduates in health promotion.
AB  - There is much support for health promotion in Canada, but not much is known about
      the various academic programs in this field or of their impact on the practice of
      community health. A census survey was conducted in 1991 to determine the career
      paths of graduates of the MHSc program in Health Promotion at the University of
      Toronto. Findings from the study indicate that the career paths of graduates
      change following completion of their degree. They are more likely to work in
      health organizations other than hospital or treatment settings, to have more
      responsibility and authority in their positions as reflected by changes in job
      titles and to utilize a wider range of health promotion strategies and methods in
      their work following graduation. The findings indicate that graduate training in
      health promotion has a positive effect on the planning, implementation and
      evaluation of community health programs.

PMID- 7728709
TI  - Characteristics, employment status, and scope of duties of community health
      representatives: a survey of graduates.
AB  - Alberta Vocational College in Lac La Biche started the Community Health
      Representative (CHR) program in 1973 to train public health para-professionals to
      act as community health educators in aboriginal communities. A follow-up study of
      graduates of the program was undertaken in 1993 to determine the extent to which
      the program meets its stated objectives. Study results show that employment
      status, location of employment and scope of duties of responding CHR graduates
      are consistent with the original purpose of the program.

PMID- 7728710
TI  - Public health nursing or community health nursing: examining the debate.

PMID- 7728711
TI  - Service models in community-based health: some findings from a literature review.
AB  - The findings from a review of the literature on community-based health services
      in Canada in 1991 indicate that two systems of health care exist side by side:
      the clinical care of the sick and the supportive care of those seeking to keep
      well. Organizational models of clinical care have not altered much since the
      introduction of health insurance. The medical profession has been resistant to
      changing traditional forms of practice organization from fee-for-service
      businesses treating individuals in isolation to components of an integrated
      comprehensive health care system. Traditional public health departments offering
      supportive and preventive care have been more ready to adapt to change. They are
      now working closely with provincial continuing-care organizers to provide home
      care for those who might otherwise need institutional care; however they are not
      closely linked with the clinical care services. More recently, public health
      departments have engaged in the health promotion movement to give citizens
      increased control over the conditions affecting their health. Yet we perceived a
      conflict between the rhetoric and the reality of their work.

PMID- 7728712
TI  - [Resistance of lice to insecticides: a serious public health problem].

PMID- 7728713
TI  - A comprehensive evaluation of the 1993 city of Toronto smoking by-laws.
AB  - Effective January 1, 1993, the City of Toronto's two smoking by-laws--one
      regarding workplaces and another regarding public places--were replaced and
      amended respectively. Smoking is now prohibited in all workplaces (unless in a
      designated smoking area), and in at least 50% of eating areas in restaurants.
      Through a workplace telephone survey and restaurant inspection records, the
      implementation and enforcement of the by-laws were evaluated. Eighty-three per
      cent of the workplaces were completely smoke-free and 7% had restricted smoking
      to a designated area. A majority (76%) of the managers and owners were in favour
      of regulatory controls on smoking in workplaces. Eighty-six per cent of
      restaurants complied with requirements for a minimum 50% smoke-free area and
      signage, and nearly 4% of the sampled restaurants banned smoking throughout the
      entire premises even though this is not currently required.

PMID- 7728714
TI  - Change in smoking prevalence among pregnant women 1982-93.
AB  - Maternal smoking is the most prevalent risk factor for low birthweight in Canada.
      This study compared the prevalence of maternal smoking before and during
      pregnancy from 1983 to 1992. Population-based surveys of 3,296 women during six
      months in 1983 and 7,940 women during 12 months in 1992 were conducted in Ottawa
      Carleton using a self-administered questionnaire completed in the hospital
      postpartum period. The proportion of women smoking after the first trimester of
      pregnancy decreased from 28.5% in 1983 to 18.7% in 1992. This difference was due
      mainly to a reduction in the proportion of women who smoked before pregnancy
      (37.4% to 26.4%). Another factor was that more women stopped smoking early in
      pregnancy (23.9% to 29.2%). Gradients in levels of smoking by age, education,
      marital status and poverty level still exist; however, this is true for the
      general population. Programs to decrease smoking in pregnancy should continue to
      focus on reducing smoking among women in general and among those in the
      preconception and early stages of pregnancy in particular.

PMID- 7728715
TI  - Importance of physician's role highlighted in survey of women's breast screening
      practices.
AB  - OBJECTIVE: To describe women's breast screening knowledge, attitudes, intentions
      and practices. DESIGN: Telephone survey. PARTICIPANTS: Random population-based
      sample of 383 women aged 50 to 69, living in Ottawa-Carleton, and having no
      history of breast cancer. Participation rates were 81%. RESULTS: Only 47%
      reported having had a mammogram within the two years before the survey, and 57%
      had received a physical breast exam within the previous year. Intentions to
      arrange screening were positively correlated to income, previous mammography,
      encouragement to have a mammogram, knowledge, knowing a person with breast
      cancer, an absence of negative attitudes (i.e., mammograms unnecessary), and low
      decisional conflict. CONCLUSIONS: Improvements in participation rates will be
      achieved only if women are convinced of the need for screening, and physicians
      encourage them to be screened.

PMID- 7728716
TI  - The effects of inspection frequency and food handler education on restaurant
      inspection violations.
AB  - The effectiveness of restaurant inspections and food handler education are not
      known. Consequently, the optimal frequency of neither has been determined. Thirty
      randomly selected restaurants from seven health units in three provinces were
      inspected by one of three senior inspectors. A questionnaire was used to collect
      the data. The violation score worsened when the time since last inspection was
      greater than 12 months, but did not worsen when the interval was shorter. Those
      restaurants in which supervisors and food handlers had completed food handler
      education courses had better inspection scores than those without. Restaurants
      whose food handlers had food service education had better scores only for time
      and temperature violations. These outcomes were all significant in a multiple
      regression model. The duration of most education courses was under five days. The
      time since the last food service education course was not significant. Routine
      inspections should be done yearly. Food service education should be offered to
      both supervisors and food handlers.

PMID- 7728717
TI  - Differences in the history of public health in 19th century Canada and Britain.

PMID- 7728718
TI  - Environmental survey of RCMP detachment building in Powell River, B.C.,
      implicated in a cancer cluster.
AB  - The rationale and approach are presented that were used to investigate the Powell
      River RCMP detachment building, perceived to have a higher than normal cancer
      incidence and whose occupants demanded to know whether the building was safe to
      work in. On the basis of the history of the building and the cancers observed, a
      set of carcinogens were looked for in areas where the worst conditions were
      expected. A positive result would initiate a second more in-depth survey. This
      was done for Fyrol-PCF, which was shown to be a contaminant of the charcoal
      adsorption tubes used. The results of the survey indicated a safe work
      environment. The chemical analyses, complemented by the bioassay and comparison
      with a recognizable control site, were found to be most effective in the
      acceptance of the results by the public. The conclusions from this survey were
      confirmed by the findings of an epidemiological survey.

PMID- 7728719
TI  - Bicycle helmet use and compliance: a northeastern Ontario roadside survey.
AB  - OBJECTIVE: To determine the prevalence of helmet use, compliance with helmet
      wearing recommendations and attitudes to bicycle helmet legislation in a northern
      Ontario community. DESIGN: Prospective roadside survey of pedal cyclists.
      PARTICIPANTS: Cyclists riding in the city of Sudbury completed a survey and
      trained interviewers examined helmet fit. RESULTS: Of 1134 cyclists encountered
      at 28 locations; 472 (42%) completed surveys. Males predominated and the mean age
      was 19.7 years. Overall, helmet use was 20% but helmet ownership was higher
      (32%). Only 49% of helmets were worn correctly. Support for legislation for those
      under the age of 16 (81%) and for all ages (57%) was high. CONCLUSIONS: Helmet
      use in this community is low; one third of helmet owners were found not to be
      using helmets regularly. Efficacy was reduced by nonadherence to helmet-wearing
      standards. Education aimed at correcting these findings should be included in
      safety campaigns.

PMID- 7728720
TI  - The effects of regular moderate to vigorous physical activity on student
      outcomes: a review.
AB  - Studies on the effects of regular (three to five times per week) periods of
      moderate to vigorous physical activity (MVPA) on the health, academic
      performance, attitudes and classroom behaviour of children at school are
      reviewed. Conclusions from the literature provide a basis for enhancement of
      school-based physical education programs that are currently considered to lack
      sufficient intensity, duration and frequency to benefit the children involved.
      The review not only confirms the value of and need for inclusion of MVPA in
      physical education programs but also shows the feasibility of doing so, to the
      advantage of both students and teachers.

PMID- 7728721
TI  - Measuring drug effectiveness by default: the case of Bendectin.
AB  - In 1983, Bendectin was voluntarily removed from the market by Merrell Dow
      Pharmaceuticals Inc. because of the many product liability suits pending.
      Earlier, 10 to 25% of pregnancies were exposed to Bendectin and over the years
      the drug was used in as many as 33 million pregnancies. The scientific evidence
      available pointed to the safety of Bendectin. This article considers some of the
      effects of the withdrawal of the drug. In 1983, hospital admissions for excessive
      vomiting in pregnancy per thousand live births rose by 37% over 1980-82 ratios
      and by 50% in 1984. In the United States, hospitalization rose by similar
      amounts. A rough estimate of excess hospital costs over the years 1983-87 is $16
      million for Canada and $73 million for the U.S. Such estimates do not take into
      consideration other costs, such as extra physician visits, increased absenteeism
      from work, and the effect on quality of life of the pregnant woman and her
      family. No decrease in rates of congenital malformations could be shown to offset
      this increased cost to society.

PMID- 7728722
TI  - [Suicide and mental disorders].

PMID- 7728723
TI  - Complications of chronic uterine torsion in a mare.

PMID- 7728724
TI  - Bovine colostrum as a cause of hemolytic anemia in a lamb.

PMID- 7728725
TI  - Peracute gangrenous mastitis and cheilitis associated with enterotoxin-secreting
      Staphylococcus aureus in a goat.

PMID- 7728726
TI  - Proventricular-ventricular impaction in an ostrich chick.

PMID- 7728727
TI  - An unusual case of hematuria in a Welsh corgi.

PMID- 7728728
TI  - Juvenile bovine angiomatosis in the mandible.

PMID- 7728729
TI  - Prokinetic drugs: metoclopramide and cisapride.

PMID- 7728730
TI  - Veterinary medical imaging: other considerations in critical thinking.

PMID- 7728731
TI  - Preferred treatment for giardiasis.

PMID- 7728732
TI  - Veterinary medical imaging: other considerations in critical thinking.

PMID- 7728733
TI  - An ethicist's commentary on whether veterinarians employed by large corporate
      entities can practise ethically.

PMID- 7728734
TI  - Twin pregnancy diagnosis in Holstein cows: discriminatory powers and accuracy of
      diagnosis by transrectal palpation and outcome of twin pregnancies.
AB  - The objective of this prospective cohort study was to determine the sensitivity,
      specificity, accuracy, and predictive value of twin pregnancy diagnosis by rectal
      palpation and to examine fetal survival, culling rates, and gestational lengths
      of cows diagnosed with twins. In this prospective study, 5309 cows on 14 farms in
      California were followed from pregnancy diagnosis to subsequent abortion or
      calving. The average sensitivity, specificity, accuracy, and predictive value of
      twin pregnancy diagnosis were 49.3%, 99.4%, 96.0%, and 86.1%, respectively. The
      abortion rate for single pregnancies of 12.0% differed significantly from those
      for bicornual twin pregnancies and unicornual twin pregnancies of 26.2% and
      32.4%, respectively (P < 0.05). The early calf mortality between cows calving
      with singles (3.2%) and twins (15.7%) were significantly different (P < 0.005).
      The difference in fetal survival between single pregnancies and all twin
      pregnancies resulted in 0.42 and 0.29 viable heifers per pregnancy, respectively.
      The average gestation for single, bicornual, and unicornual pregnancies that did
      not abort before drying-off was 278, 272, and 270 days, respectively. Results of
      this study show that there is an increased fetal wastage associated with twin
      pregnancies and suggest a need for further research exploring management
      strategies for cows carrying twins.

PMID- 7728735
TI  - Transmission of Loma salmonae (Microsporea) to chinook salmon in sea water.
AB  - Transmission studies were conducted to determine if Loma salmonae was
      transmissible in sea water. Transmission of L. salmonae to chinook salmon
      (Oncorhynchus tshawytscha) held in sea water was achieved by exposing fish to
      macerated, infected gill tissue. Fish were exposed in seawater in a flow-through
      aquarium, and the infection was detected as soon as 5 wk after exposure. Heavily
      infected fish exhibited numerous xenomas in the branchial arteries, central
      venous sinusoids, and within the blood channels of the lamellae. The pathological
      changes were similar to those seen in pen-reared salmon with L. salmonae
      infections. The infection was not observed in Atlantic salmon (Salmo salar),
      Pacific herring (Clupea pallasi, family Clupeidae), or shiner perch (Cymatogaster
      aggregata, family Embiotocidae), experimentally exposed using identical methods.
      This study suggests that L. salmonae is transmissible to chinook salmon in
      seawater netpens. Fish farmers and fish health specialists should consider this
      possibility when developing and implementing strategies to control the infection.

PMID- 7728736
TI  - Carcinoma associated mucins: molecular biology and clinical applications.
AB  - Mucin is a viscous secretion of glycoproteins secreted by epithelial cells of
      normal and cancerous tissues. Excessive and abnormal mucin synthesis has been
      observed in a number of cancers. The conformation and configuration of the
      surface carbohydrates play a key role in generating multiple forms of mucins in
      different cancers. The epitopes on the surface of mucin are recognized by
      antibodies present in different cancer cells. The primary structure of some of
      the cancer-associated mucins has been determined by molecular cloning of their
      complementary DNAs. The detection methods for cancer-associated mucins and their
      clinical applications are discussed.

PMID- 7728737
TI  - DNA fingerprinting analysis of radiation-induced rat skin tumors.
AB  - DNA fingerprinting analysis was performed on rat skin tumors induced by high
      linear energy transfer neon ion radiation. Most of these tumors (13/15) showed
      DNA-fingerprint variability between independently isolated tumors from the same
      animal. These changes include multiple band shifts and extra bands. Comparisons
      of DNA fingerprints were also made on successive biopsy samples from the same
      tumor. Each of 3 neon-induced tumors and 2 of 8 electron (low LET) induced tumors
      showed progressive loss of amplified sequences, gain of amplified sequences,
      deletions, band shifts, and the appearance of extra bands in progressive
      biopsies. These results provide evidence for LET-specific effects on genomic
      instability in radiation-induced rat skin tumors.

PMID- 7728738
TI  - Erythrocyte antioxidant enzyme activity in CMF treated breast cancer patients.
AB  - Most of breast cancer patients are treated with CMF, which is a combination of
      three anticancer agents, cyclophosphamide, methotrexate and 5-fluorouracil.
      Metabolites of CMF induce lipid peroxidation by inactivating the antioxidant
      enzymes, thereby rendering the system inefficient in management of the free
      radical attack. Acrolein and phosphoramide mustard are the metabolites of
      cyclophosphamide which are among the causative agents which reduce the activity
      of superoxide dismultase, catalase, glutathione peroxidase, glutathione
      reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase in
      erythrocytes of CMF treated breast cancer patients.

PMID- 7728739
TI  - Formation of 8-hydroxyguanine in DNA during mitomycin C activation.
AB  - DNA damage caused indirectly via reactive oxygen species generated during
      reductive activation of mitomycin C was evaluated. This oxidative DNA damage was
      measured by determining the formation of 8-hydroxyguanine in DNA exposed to
      chemically or enzymatically activated mitomycin C. The level of 8-hydroxyguanine
      was measured indirectly by determining formamidopyrimidine-DNA glycosylase
      sensitive sites induced in plasmid DNA exposed to mitomycin C and directly by a
      32P-postlabeling assay for the modified base. Activation of mitomycin C by sodium
      borohydride in air, by H2/Pt, or xanthine oxidase in N2 caused increases in the
      level of 8-hydroxyguanine. The extent of the increase varied according to the
      incubation conditions with the greatest increase being observed in DNA exposed to
      mitomycin C activated under hypoxic conditions. These results support a possible
      indirect mechanism for DNA damage caused by mitomycin C that is mediated by
      reactive oxygen species.

PMID- 7728740
TI  - Inhibitory effect of mevalonate on the EGF mitogenic signaling pathway in human
      breast cancer cells in culture.
AB  - The relationship between the effects of EGF and mevalonate on proliferation of
      the breast cancer cell line Hs578T was investigated. When Hs578T cells were
      depleted of serum their proliferation was drastically retarded. This was
      partially counteracted by insulin or IGF-1 but not by EGF. However, if the
      activity of HMG-CoA reductase was inhibited, there was a significant increase in
      DNA synthesis of EGF-treated cells. This effect was not seen in cells stimulated
      by insulin or IGF-1, and was prevented by addition of mevalonate. The results
      suggest that mevalonate, or some of its products, inhibits steps in the EGF
      signal pathway.

PMID- 7728741
TI  - Calcium ion and the membrane potential of tumor cells.
AB  - Calcium ion affects ion permeability and membrane potential among many other
      aspects of cell function. Initial effects of increasing extracellular calcium
      upon membrane potential were studied in a quail fibrosarcoma (QT35) where calcium
      had a dose dependent effect, and normal quail fibroblasts, where there was little
      effect. Comparisons were then made in six different human hepatocellular
      carcinomas (Tong, HepG2, Hep3B, PLC/PRF/5, Mahlavu, and HA22T) in response to
      smaller changes in concentration. There were insignificant changes in membrane
      potential in two cell lines and significant elevations in four. Cytolysis by
      natural killer cells also declined in rough proportion to the increase in
      membrane potential. The less differentiated hepatocellular carcinoma cells have
      both higher baseline membrane potentials and a greater potential increase to
      increased calcium. By contrast, more highly differentiated tumor cells had
      paradoxically smaller membrane potentials and along with normal cells had small
      potential responses to calcium increases.

PMID- 7728742
TI  - Effect of modifiers of arachidonic acid metabolism on radiation transformation
      and eicosanoid formation in C3H/10T1/2 cells.
AB  - In these studies, we performed experiments designed to elucidate the role that
      arachidonic acid metabolism plays in oncogenic transformation in vitro. The
      levels of TxB2 and 6-keto-PGF1 alpha were elevated in cells treated with X-rays.
      A significant increase in the levels of these eicosanoids was observed following
      irradiation. Treatment of cells with the anticarcinogenic protease inhibitors,
      Bowman-Birk Inhibitor (BBI) and N-tosyl-L-phenylalanine chloromethyl ketone
      (TPCK), significantly reduced the levels of TxB2 and 6-keto-PGF1 alpha present.
      Indomethacin treatment significantly reduced the levels of TxB2 and 6-keto-PGF1
      alpha to < 10% of those present in untreated or irradiated cells. We also report
      that addition of lipoxygenase or minoxidil [a selective inhibitor of prostacyclin
      (PGl2) synthetase] led to a highly significant decrease in transformation. In
      addition, minoxidil treatment resulted in a significant reduction in the levels
      of 6-keto-PGF1 alpha in irradiated cells. Our results suggest the hypothesis that
      the relative levels of 6-keto-PGF1 alpha are important in radiation induced
      transformation.

PMID- 7728743
TI  - Inhibition of apoptosis during development of colorectal cancer.
AB  - Colorectal tumorigenesis proceeds through an accumulation of specific genetic
      alterations. Studies of the mechanism by which these genetic changes effect
      malignant transformation have focused on the deregulation of cell proliferation.
      However, colorectal epithelial homeostasis is dependent not only on the rate of
      cell production but also on apoptosis, a genetically programmed process of
      autonomous cell death. We investigated whether colorectal tumorigenesis involved
      an altered susceptibility to apoptosis by examining colorectal epithelium from
      normal mucosa, adenomas from familial adenomatous polyposis, sporadic adenomas,
      and carcinomas. The transformation of colorectal epithelium to carcinomas was
      associated with a progressive inhibition of apoptosis. The inhibition of
      apoptosis in colorectal cancers may contribute to tumor growth, promote
      neoplastic progression, and confer resistance to cytotoxic anticancer agents.

PMID- 7728744
TI  - Up-regulation of the oligosaccharide sialyl LewisX: a new prognostic parameter in
      metastatic prostate cancer.
AB  - Metastatic prostate cancer has an unpredictable long-term prognosis. At present,
      there are few specific predictors to indicate the outcome for the individual
      patient. We have studied immunoreactivity for type-2 carbohydrate structures,
      known to be involved in various cell adhesion processes, in patients with
      metastatic prostate cancer. One group of patients (n = 26) did not progress
      within 3 years after orchiectomy, while another group of patients (n = 33)
      progressed within 1 year following castration and survived less than 2 years.
      Among the parameters studied, sialyl LewisX carbohydrate up-regulation was the
      only variable showing significant association with poor prognosis (P < 0.01).
      Sialyl LewisX discriminated between these two outcome groups with 71%
      predictability and 96% specificity. Our results indicate that up-regulation of
      sialyl LewisX is associated with hormonal-resistant, aggressive disease. This
      prognostic marker may, therefore, have an important role in selecting proper
      treatment for patients with metastatic prostate cancer.

PMID- 7728745
TI  - Decreased expression and function of alpha-2 macroglobulin receptor/low density
      lipoprotein receptor-related protein in photodynamic therapy-resistant mouse
      tumor cells.
AB  - Parental and photodynamic therapy (PDT)-resistant mouse, radiation-induced
      fibrosarcoma cell lines were evaluated using mRNA differential display in an
      attempt to identify unique transcripts. We detected one transcript that was
      consistently present in the parental cells but absent in PDT-resistant cells. The
      transcript was cloned, sequenced, and identified as alpha-2 macroglobulin
      receptor/low density lipoprotein receptor-related protein (alpha-2 MR/LRP).
      Northern and Western immunoblot analysis confirmed that receptor expression was
      present in the parental cell line but barely detectable in PDT-resistant cells.
      Functionality of the receptor was evaluated by exposing cells to Pseudomonas
      exotoxin A. alpha-2 MR/LRP is responsible for Pseudomonas exotoxin A
      internalization, and only the parental cells exhibited toxin-mediated
      cytotoxicity. The binding and endocytosis of activated alpha-2 macroglobulin and
      lipoproteins by alpha-2 MR/LRP are consistent with modulating uptake and
      localization of photosensitizers. Our results demonstrate that PDT-resistant
      murine tumor cells exhibit minimal alpha-2 MR/LRP activity and suggest that this
      receptor plays a role in PDT sensitivity by modulating photosensitizer uptake
      and/or subcellular localization.

PMID- 7728746
TI  - Tumor regression in monoclonal antibody-treated patients correlates with the
      presence of anti-idiotype-reactive T lymphocytes.
AB  - Treatment of cancer patients with unconjugated mAbs directed against tumor
      associated antigens is considered passive immunotherapy due to the main suggested
      effector mechanisms: antibody-dependent cellular cytotoxicity, complement
      dependent cytolysis, and apoptosis. The therapeutic antibody (ab1) may, however,
      also give rise to an idiotypic network response, i.e., an immunizing effect.
      Induced anti-idiotypic antibodies (ab2) mimicking the epitope that ab1 recognizes
      might subsequently induce an anti-anti-idiotypic humoral (ab3) and T-cell (T3)
      response recognizing the nominal tumor-associated antigen. Twenty-four patients
      with metastatic colorectal carcinoma were treated with MAb17-1A against the tumor
      associated antigen GA733-2 and were analyzed for the induction of T3 cells. Five
      of the patients responded to mAb therapy with tumor regression. These five
      patients all had T cells specifically recognizing human ab2 (DNA synthesis) after
      treatment, while all nonresponding patients lacked such T cells. Four of the five
      patients with ab2-reactive T cells also showed induction of T cells recognizing
      GA733-2. The association between T3 cells and tumor regression was highly
      significant (P = 0.0005). Thus, induction of T3 cells might be an important
      secondary antitumor effector function of therapy with unconjugated mAbs. Antibody
      therapy may therefore also be considered active specific immunotherapy.

PMID- 7728747
TI  - Deletion mapping in squamous cell carcinomas of the esophagus defines a region
      containing a tumor suppressor gene within a 4-centimorgan interval of the distal
      long arm of chromosome 9.
AB  - Recent studies in our laboratory indicated that inactivation of a putative tumor
      suppressor gene on chromosome 9q is likely to be associated with an early step of
      esophageal carcinogenesis. To further define a region containing the putative
      tumor suppressor gene, we have examined loss of heterozygosity in 37 esophageal
      squamous cell carcinomas using 14 microsatellite markers mapped to 9q31-q34.1.
      Loss of heterozygosity was observed in 30 (81%) of 37 tumors at one or more of
      the loci examined, and partial or interstitial deletions at 9q31-q34.1 were
      detected in 13 of these tumors. On the basis of these results, we constructed a
      detailed deletion map and defined a commonly deleted region between the D9S262
      and D9S154 loci at 9q31-q32. The genetic distance between these two loci is
      estimated to be approximately 4 cM.

PMID- 7728748
TI  - Loss of imprinting in hepatoblastoma.
AB  - We and others have described loss of imprinting (LOI) of the insulin-like growth
      factor II (IGF2) gene in 70% of Wilms' tumors (WT), an embryonal kidney tumor,
      and we have also found LOI of the H19 gene in 29% of WTs. In WT, LOI of IGF2 is
      coupled to down-regulation of H19. LOI of IGF2 has subsequently been described in
      a second embryonal neoplasm, rhabdomyosarcoma. However, the hypothesis that LOI
      is a general feature of embryonal tumors is challenged by a report of absence of
      LOI in three hepatoblastomas (S. M. Davies, Cancer Res., 53: 4781-4783, 1993). We
      identified five hepatoblastomas informative for a transcribed polymorphism of the
      IGF2 gene. One tumor showed LOI of IGF2, in contrast to the previous report. That
      tumor also showed LOI of H19, further documenting a role for this gene in
      imprinting disturbances in cancer. However, in contrast to WT, LOI in
      hepatoblastoma was not associated with down-regulation of H19. Thus, IGF2 and H19
      expression can be uncoupled in tumors with LOI.

PMID- 7728749
TI  - Alternative splicing of MLH1 messenger RNA in human normal cells.
AB  - The hMLH1 protein, composed of 756 amino acids, is the human homologue of the
      bacterial DNA mismatch repair protein MutL, and germ line mutations of the hMLH1
      gene have been identified in kindreds with hereditary nonpolyposis colorectal
      cancer. We have detected three alternatively spliced forms of hMLH1 mRNA in
      normal lymphocytes and tissues. One of the spliced forms lacks the coding region
      of hMLH1 from codons 227 to 295 and the two other transcripts are predicted to
      encode two truncated proteins retaining the 264 and 226 N-terminal amino acids of
      hMLH1, respectively. The biological significance of this alternative splicing
      remains to be established.

PMID- 7728750
TI  - Relationship between radiation-induced G1 phase arrest and p53 function in human
      tumor cells.
AB  - Three widely studied cell lines were used to examine the nature of the G1 arrest
      induced in human tumor cells by ionizing radiation and its relation to p53
      status. Cell lines MCF-7 and RKO express wild-type p53, whereas HT29 expresses
      mutant p53. Exponentially growing cells were irradiated with 6 Gy, and the
      progression of G1 cells into S phase was monitored at regular intervals by flow
      microfluorimetric and continuous labeling autoradiographic techniques. In some
      experiments, cells were incubated with Colcemid prior to irradiation in order to
      block them in mitosis and to prevent the accumulation of cells in the second post
      irradiation G1 phase. No evidence of a significant arrest at the first post
      irradiation G1-S checkpoint was observed in any of the three cell lines. These
      results suggest that p53 function alone does not control the progression of
      irradiated human tumor cells from G1 into S during the first post-irradiation
      cell cycle. In particular, we found no evidence that radiation induced a
      prolonged G1 arrest in tumor cells expressing wild-type p53 as has been reported
      by some investigators.

PMID- 7728751
TI  - Inhibition of tumor cell invasion through matrigel by a peptide derived from the
      domain II region in urinary trypsin inhibition.
AB  - Urinary trypsin inhibitor (UTI) has a multipotent inhibitory effect on proteases
      such as trypsin, chymotrypsin, plasmin, human leukocyte elastase, or
      hyaluronidase. UTI can bind easily to its receptors on various types of tumor
      cells (human ovarian cancer HOC-I cells, human choriocarcinoma SMT-cc1 cells, and
      murine Lewis lung carcinoma 3LL cells). Our results show that the UTI receptors
      of some tumor cells have a possible role in modulating plasmin activity on the
      cell surface and prevention of tumor cell invasion and metastasis (H. Kobayashi
      et al., J. Biol. Chem., 269; 20642-20647, 1994). UTI interacts with tumor cells
      as a negative modulator of the invasive cells. We investigated whether this
      effect may be mediated by UTI binding to the cell surface receptors. In addition,
      the role of peptide sequences from each UTI domain and their interaction with
      tumor cells were investigated. UTI derivatized with biotin or FITC was taken up
      by tumor cells in a dose-dependent manner. This cell association was inhibited
      with a monoclonal antibody D1, which specifically recognizes NH2 terminus (domain
      I) of UTI. The binding was inhibited by fluid phase UTI, but not HI-8, COOH
      terminus (domain II) of UTI, suggesting that UTI binds to cells through a site in
      the UTI domain I. Furthermore, we found that UTI, HI-8 and a number of peptides
      containing Arg-Gly-Pro-Cys-Arg-Ala-Phe-Ile promoted the inhibition of tumor cell
      invasion. This site corresponds to the plasmin-inhibiting domain within HI-8. The
      possibility that UTI binding to tumor cells might be involved in the prevention
      of tumor cell invasion in vitro was excluded since HI-8, lacking domain I,
      promotes the inhibition of tumor cell invasion with essentially the same affinity
      as UTI. All these data allow us to conclude that inhibition of tumor cell
      invasion is mediated by domain II, which possesses anti-plasmin activity.

PMID- 7728752
TI  - Expression of the gastrin-releasing peptide receptor confers a growth response to
      bombesin in immortalized human bronchial epithelial cells.
AB  - We have introduced a human gastrin-releasing peptide receptor expression vector
      into an immortalized human bronchial epithelial cell normally unresponsive to the
      ligand bombesin. Successfully transfected cells express specific binding sites at
      a density similar to that found at the surface of human lung cancer cells and
      show an elevation of intracellular calcium concentration in response to bombesin.
      We found that cellular strains expressing the receptor showed a growth
      stimulation in response to bombesin in proportion to cell surface receptor
      density. We conclude that expression of bombesin receptors contributes to the
      growth potential of human bronchial epithelial cells.

PMID- 7728753
TI  - Molecular insights into cancer invasion: strategies for prevention and
      intervention.
AB  - The diagnosis and treatment of solid tumors usually begins at a late stage when
      most patients already have occult or overt metastasis. Many years of cancer
      progression precede diagnosis of most solid tumors. Novel noncytotoxic
      therapeutics may be specially suited for administration during this interval. An
      important window of intervention can be defined as the period during which
      transition from a hyperproliferative state to acquisition of the capacity for
      invasion and metastasis occurs. Investigation of the molecular basis of invasion
      is uncovering strategies for delaying progression of preinvasive carcinoma and
      treatment of primary tumors and established metastasis. Although tumor cell
      invasion might not be rate limiting for the growth of metastasis, anti-invasive
      agents can block tumor angiogenesis and thereby indirectly block metastasis
      growth. Two classes of molecular anti-invasion targets exist: (a) cell surface
      and extracellular proteins, which mediate sensing, adhesion, and proteolysis; and
      (b) signal transduction pathways, which regulate invasion, angiogenesis, and
      proliferation. Both categories of targets yield treatment approaches that are now
      being tested in the clinic. Metalloproteinase inhibitors, such as BB94, are based
      on the recognition that metalloproteinases play a necessary role in invasion and
      angiogenesis. The orally active signal transduction inhibitor
      carboxyamidotriazole modulates non-voltage-gated calcium influx-regulated signal
      pathways and reversibly inhibits tumor invasion, growth, and angiogenesis.
      Blockade of invasion, angiogenesis, or cellular signal pathways is likely to
      generate a cytostatic, rather than a cytotoxic effect. Cytostatic therapy
      constitutes an alternative paradigm for clinical translation that may complement
      conventional cytotoxic therapy. For patients with newly diagnosed solid tumors,
      long-term cytostatic therapy could potentially create a state of metastasis
      dormancy or delay the time to overt relapse following cytotoxic agent-induced
      remission. Clinical toxicity and pharmacology using oral cytostatic agents in
      phase I trials and in adjuvant settings will provide an important foundation for
      the translation of this approach to the preinvasive carcinoma period.

PMID- 7728754
TI  - Natural estrogens induce modulation of microtubules in Chinese hamster V79 cells
      in culture.
AB  - Natural estrogens and their derivatives comprising 30 compounds in total were
      tested for their ability to induce microtubule disruption in Chinese hamster V79
      cells. The cytoplasmic microtubule networks were examined by the indirect
      immunofluorescence method using anti-beta-tubulin antibody. The effective
      concentrations of 17 beta-estradiol (E2-17 beta) and 17 alpha-estradiol required
      for the induction of microtubule distribution in 50% of the cells (EC50) in 1 h
      were 10 and 9 microM for V79 cells, respectively, and 2-methoxyestradiol showed
      the strongest activity (EC50 2 microM) among the tested compounds including the
      catechol estrogens 2-hydroxyestradiol, 4-hydroxyestradiol, 2-hydroxyestrone, and
      4-hydroxyestrone. The estrone series of estrogens showed relatively low activity
      for disruption of microtubule networks compared with E2-17 beta, whereas 3-deoxy
      3-methylestradiol showed almost the same EC50 value as E2-17 beta. There was a
      correlation between the EC50 values of the compounds and their growth-inhibitory
      activities. The presence of 1 microM taxol in culture protected against 50 microM
      E2-17 beta-induced microtubule disruption. Cycloheximide and actinomycin D had no
      preventive action on the effect of E2-17 beta, suggesting that the microtubule
      disruptive effect of E2-17 beta is not associated with newly synthesized proteins
      and mRNAs. The present results indicate that some natural estrogens cause
      microtubule disruption in a nongenomic manner.

PMID- 7728755
TI  - Marked differences in the role of O6-alkylguanine in hprt mutagenesis in T
      lymphocytes of rats exposed in vivo to ethylmethanesulfonate, N-(2-hydroxyethyl)
      N-nitrosourea, or N-ethyl-N-nitrosourea.
AB  - The role of DNA alkylation at the O6 position of guanine in the induction of gene
      mutations in vivo was studied in the hprt gene of rat T-lymphocytes from spleen
      exposed in vivo to the monofunctional ethylating agents ethylmethanesulfonate
      (EMS) and N-ethyl-N-nitrosourea (ENU), or the hydroxyethylating agent N-(2
      hydroxyethyl)-N-nitrosourea (HOENU). All chemicals showed an exposure-dependent
      increase in hprt mutant frequency. HOENU and ENU, however, were much more
      mutagenic than EMS when compared at equimolar levels. DNA sequence analysis was
      performed on PCR products of hprt cDNA from 40 EMS-, 35 HOENU-, and 46 ENU
      induced 6-thioguanine-resistant T-lymphocyte clones. Thirty EMS-induced mutants
      contained a single base pair substitution with GC to AT transitions being the
      predominant type of mutation (26 of 30) which are probably caused by mispairing
      of O6-ethylguanine with T during DNA replication. No strand specificity of
      mutated G's among GC to AT transitions was observed. Twenty-three HOENU- and 42
      ENU-induced mutants contained a single base pair substitution. In contrast to
      EMS, GC to AT transitions were found at a low frequency, 4 of 23 for HOENU and 5
      of 42 for ENU, indicating that O6-hydroxyethylguanine and O6-ethylguanine are
      less important in HOENU- and ENU-induced mutagenesis in vivo, respectively. Also
      here no strand bias for mutated G's was observed, although the number of this
      type of mutation was limited. The most frequently induced base pair alterations
      by HOENU and ENU were transversions at AT base pairs, 16 of 23 and 28 of 42,
      respectively, with AT to TA being the predominant type of mutation. In both ENU
      and HOENU mutational spectra, an extreme strand bias for mutated T's toward the
      nontranscribed strand was found. The results suggest that DNA damage induced in
      rat T-lymphocytes in vivo by HOENU and ENU is processed in similar ways.

PMID- 7728756
TI  - Autocrine transforming growth factor alpha is dispensible for v-rasHa-induced
      epidermal neoplasia: potential involvement of alternate epidermal growth factor
      receptor ligands.
AB  - Autocrine epidermal growth factor receptor activation by transforming growth
      factor alpha (TGF alpha) has been implicated in growth stimulation during
      epithelial neoplasia. Using keratinocytes isolated from mice with genetic defects
      in TGF alpha expression, we tested whether TGF alpha is required for
      transformation by the v-rasHa oncogene. Introduction of v-rasHa into primary
      epidermal cultures using a retroviral vector stimulated growth of both control
      (TGF alpha +/+, BALB/c) and TGF alpha-deficient (TGF alpha -/-, wa-1)
      keratinocytes. Moreover, v-rasHa elicited characteristic changes in marker
      expression (keratin 1 was suppressed; keratin 8 was induced), previously shown to
      be associated with epidermal growth factor (EGF) receptor activation, in both TGF
      alpha +/+ and TGF alpha -/- keratinocytes. v-rasHa markedly increased secreted (>
      10-fold) and cell-associated (2-3-fold) TGF alpha levels in keratinocytes from
      TGF alpha +/+ and BALB/c mice, but not TGF alpha -/- or wa-1 mice. Based on
      Northern blot analysis, v-rasHa induced striking up-regulation of transcripts
      encoding the additional EGF family members amphiregulin, heparin-binding EGF-like
      growth factor, and betacellulin in cultured keratinocytes from all four mouse
      strains. Interestingly, in addition to the normal 4.5-kilobase TGF alpha
      transcript, wa-1 keratinocytes expressed two additional TGF alpha transcripts,
      4.7 and 5.2 kilobases long. All three transcripts were up-regulated in response
      to v-rasHa, as well as exogenous TGF alpha or keratinocyte growth factor
      treatment, and were also detected in RNA isolated from wa-1 brain and skin. In
      vivo, v-rasHa keratinocytes from control as well as TGF alpha-deficient mice
      produced squamous tumors when grafted onto nude mice, and these lesions expressed
      high levels of amphiregulin, heparin-binding EGF-like growth factor, and
      betacellulin mRNA, regardless of their TGF alpha status. These findings indicate
      that TGF alpha is not essential for epidermal neoplasia induced by the v-rasHa
      oncogene and suggest that another EGF family member(s) may contribute to
      autocrine growth stimulation of ras-transformed keratinocytes.

PMID- 7728757
TI  - RG-2 glioma growth attenuation and severe brain edema caused by local production
      of interleukin-2 and interferon-gamma.
AB  - Two aspects of cytokine therapy of intracerebral tumors are considered in this
      study: modulation of tumor growth in vivo and central nervous system toxicity.
      Coimplantation of RG-2 glioma cells and retroviral vector producer cell lines was
      performed to provide a local source of interleukin-2 (IL-2) or IFN-gamma within
      the tumor and coinitiate an antitumor immune response. We demonstrated that local
      intratumoral production of IL-2 and IFN-gamma generates a cell-mediated antitumor
      response in vivo. This response was manifest as a diffuse infiltration of
      monocytes/macrophages, CD4+ and CD8+ T cells, and activation of microglial OX42+
      cells in intracerebral RG2 tumors. The cell-mediated antitumor immune response
      resulted in the early suppression of intracranial and subcutaneous tumor growth,
      but the effect was not sustained and there were no tumor regressions. The absence
      of increased survival of animals with intracranial tumors is explained in part by
      the severe central nervous system toxicity caused by local production of IL-2 and
      IFN-gamma. Central nervous system toxicity induced blood-brain barrier
      disruption, vasogenic brain edema, and dislocation of the brain midline
      structures, as observed by dynamic magnetic resonance imaging and direct
      measurements of tissue water content. The clinical application of IL-2 and IFN
      gamma gene transfer therapy for intracerebral tumors must consider the potential
      for severe vasogenic brain edema associated with intracerebral production of
      these cytokines.

PMID- 7728758
TI  - Rejection of tumors in mice with severe combined immunodeficiency syndrome
      determined by the major histocompatibility complex. Class I expression on the
      graft.
AB  - This study addresses the role of MHC class I molecules in the rejection of tumor
      grafts by SCID mice. Tumor cell lines, their corresponding MHC class I
      transfectants, and MHC class I-deficient mutants were inoculated to SCID mice.
      This allowed a study of tumor rejection responses in an environment with normal
      numbers of natural killer cells but largely devoid of functional T and B cells.
      C.B-17 (H-2d) SCID mice were found to reject low (10(2)) but not high (10(4))
      doses of allogeneic (H-2b) tumor cells. The introduction of H-2Dd into such
      allogeneic tumor cells abrogated the rejection response with progressive tumor
      growth as a consequence. Introduction of H-2Kd or Ld had no or only marginal
      effects. The protective ability of H-2Dd was mapped to the alpha 1/alpha 2
      domains of the molecule. H-2Dd protected allogeneic tumors from rejection also in
      C3H SCID mice of the H-2k haplotype, demonstrating that this ability was not
      dependent on H-2Dd expression in the host. Expression of endogenous H-2Kb and/or
      Db molecules partially protected wild-type allogeneic tumor cells from rejection
      since mutant allogeneic cells, devoid of class I expression, were rejected even
      after high-dose inoculation. Introduction of either allogeneic or xenogeneic
      class I molecules did not lead to rejection of otherwise MHC class I syngeneic (H
      2d) tumor cells. The observed tumor cell rejection in SCID mice was dependent on
      natural killer cells. After depletion of asialo-GM1+ cells, all inoculated tumor
      cell lines grew progressively, independently of MHC class I expression. These
      results are compatible with a model where expression of certain, but not all,
      class I molecules protect from natural killer cell-mediated rejection. There was
      no evidence for rejection occurring as a consequence of the expression of
      allogeneic or xenogeneic class I molecules on the grafted cells. MHC class I
      expression may thus influence tumor cell recognition in mice lacking T-cell
      receptor expression.

PMID- 7728759
TI  - Cloning and characterization of TCTA, a gene located at the site of a t(1;3)
      translocation.
AB  - We have cloned and characterized a novel gene at the site of a t(1;3)(p34;p21)
      translocation breakpoint in T-cell acute lymphoblastic leukemia. A cDNA for this
      gene, for which we propose the designation TCTA (T-cell leukemia translocation
      associated gene), has been cloned. TCTA mRNA is expressed ubiquitously in normal
      tissues, with the highest levels of expression seen in the kidney. The TCTA gene
      is conserved throughout evolution in organisms ranging from Drosophila to humans.
      A short open reading frame encodes a predicted M(r) 12,000 protein without strong
      homology to any previously reported proteins. Of note, genomic Southern blots
      demonstrated a reduced TCTA signal in three of four small cell lung cancer cell
      lines tested, suggesting loss of one of the two copies of the gene.

PMID- 7728760
TI  - Allelic loss of sequences from the long arm of chromosome 10 and replication
      errors in endometrial cancers.
AB  - Thirty-seven endometrial cancers were subjected to an allelotype analysis in an
      attempt to identify chromosomal regions that are lost in a significant portion of
      tumors and to identify tumors characterized by replication errors. Thirty-nine
      highly polymorphic microsatellite markers representing all chromosomal arms,
      excluding the X and the short arms of the acrocentrics, were examined. An average
      of 20 informative cases were evaluated for each marker. Genetic alterations were
      detected in 30 of the 37 tumors. Replication errors were identified in 8 tumor
      specimens. Loss of heterozygosity was observed for loci on all chromosomes
      examined with the exception of chromosomes 4 and 20. The two most frequent sites
      of loss were at the marker loci examined on 10q (40%) and 17p (29%). Six
      additional simple sequence repeat markers from 10q were genotyped in an effort to
      refine the region of 10q loss. The chromosome 10 markers used in these studies
      were physically mapped with the use of a panel of somatic hybrids that retain
      defined portions of chromosome 10. The observed patterns of loss of sequences on
      10q suggest a role for a tumor suppressor gene in the 10q23-26 region in the
      development or progression of endometrial cancers.

PMID- 7728761
TI  - Expression of c-fos in quiescent Swiss 3T3 cells exposed to aqueous cigarette
      smoke fractions.
AB  - The exposure of quiescent Swiss 3T3 cells to mainstream cigarette smoke (CS)
      trapped in PBS solution (smoke-bubbled PBS) resulted in the dose-dependent
      expression of c-fos mRNA and protein. Kinetic investigations revealed that in
      contrast to mitogens, which strongly but transiently induce the c-fos promoter
      within minutes, c-fos transcripts in cells exposed to 0.03 puffs (approximately 1
      cm3) of CS/ml of medium accumulated slowly but were still seen after 8 h; the
      maximum expression rates were between 2 and 6 h of exposure. This specific
      expression pattern appears to be the result of altered posttranscriptional as
      well as transcriptional regulation, since a strikingly increased stability of the
      c-fos message (t1/2, > or = 2 h versus < 20 min in serum-stimulated cells) in
      smoke-treated cells was observed in addition to slight transcriptional activation
      of the c-fos promoter. CS-dependent DNA damage can be excluded as the only source
      for this altered expression pattern, since inhibition of DNA strand break
      formation by either catalase or o-phenanthroline had no detectable effect on the
      CS-induced c-fos expression. The results described here, and other CS-dependent
      cellular and biochemical effects, are similar to those induced in vitro by
      okadaic acid, a specific inhibitor of cell growth-regulatory protein phosphatases
      1/2A (PP-1/2A). Hence, the effects of smoke treatment on these key enzymes were
      compared to those of okadaic acid based on the ability of cell-free extracts to
      release radiolabeled phosphate from glycogen phosphorylase a, a substrate of PP
      1/2A. Results from these experiments indicate that both treatments inhibited PP
      1/2A in a concentration- and analogous time-dependent manner. The data presented
      suggest that PP-1/2A may, at least in vitro, be targeted by water-soluble active
      compounds present in cigarette smoke.

PMID- 7728762
TI  - Microsatellite alterations in adenoma and differentiated adenocarcinoma of the
      stomach.
AB  - In order to elucidate the significance of the adenoma-carcinoma sequence in
      gastric carcinogenesis from a genetic point of view, we examined microsatellite
      alterations (replication error and loss of heterozygosity) on chromosomes 2p
      (D2S123), 3p (D3S1317), 5q (D5S409), 9p (IFNA), and 13q (D13S153) as well as p53
      gene mutations in 13 adenomas and 23 differentiated adenocarcinomas including 8
      early carcinomas of the stomach. Replication error was detected in only one of
      the adenomas (8%, 1/13) at the D5S409 locus and in none at the other loci, and
      loss of heterozygosity was also an infrequent event found in one adenoma (14%,
      1/7 informative cases) at D5S409 and in none at the other loci. A p53 gene
      mutation was detected in one (8%, 1/13) of the adenomas. Thus, microsatellite
      alterations and p53 gene mutations are rare events in adenomas. In differentiated
      adenocarcinomas, replication error was detected in 4 (17%, 4/23) at single or
      multiple loci, and loss of heterozygosity was observed frequently at D3S1317
      (25%, 3/12), D5S409 (67%, 6/9), and IFNA (26%, 5/19). Mutations in the p53 gene
      were detected in 9 (39%, 9/23) of the differentiated adenocarcinomas.
      Microsatellite alterations on several chromosomes and mutations in the p53 gene
      were frequent in differentiated adenocarcinomas, even those at an early stage.
      These results suggest that the adenoma-carcinoma sequence is relatively rare in
      gastric carcinogenesis, and that the majority of differentiated adenocarcinomas
      of the stomach may develop through a de novo pathway.

PMID- 7728763
TI  - The CAG and GGC microsatellites of the androgen receptor gene are in linkage
      disequilibrium in men with prostate cancer.
AB  - The androgen receptor genotype was determined in the white blood cell DNA of 45
      African-American, 39 non-Hispanic white, and 39 Asian (Chinese, Japanese) normal
      subjects and 68 patients with prostate cancer (57 whites), all of whom were
      residents of Los Angeles County. For each subject, we measured the number of
      repeats in the polymorphic CAG and GGC microsatellites of exon 1 of the androgen
      receptor gene. In normal subjects, the distributions of CAG and GGC
      microsatellites differed significantly among the races (two-sided P = 0.046 and <
      0.0005, respectively). The prevalence of short CAG alleles (< 22 repeats) was
      highest (75%) in African-American males with the highest risk for prostate
      cancer, intermediate (62%) in intermediate-risk non-Hispanic whites, and lowest
      (49%) in Asians at very low risk for prostate cancer. High-risk African-Americans
      also had the lowest frequency (20%) of the GGC allele with 16 repeats; the
      comparable values for intermediate-risk whites and low-risk Asians were 57% and
      70%, respectively. Consistent with the interracial variation in CAG and GGC
      distributions, there was an excess of white patients with < 22 CAG and not-16 GGC
      repeats relative to white controls (relative risk, 2.1; one-sided P = 0.08). We
      observed no association (linkage) between the two microsatellites among normal
      subjects. On the other hand, there was a statistically significant negative
      association between the numbers of CAG and GGC repeats among the prostate cancer
      patients studied (two-sided P = 0.008). Among the 47 subjects with short CAG
      alleles (< 22 repeats), 43% had long GGC alleles (> 16 repeats) whereas only 15%
      of the 20 subjects with long CAG alleles (> or = 22 repeats) had long GGC
      alleles. Overall, our data suggest a possible association between CAG and GGC
      microsatellites of the androgen receptor gene and prostate cancer development.

PMID- 7728764
TI  - Loss of P16INK4 expression is frequent in high grade gliomas.
AB  - P16INK4 is a cell cycle regulator that specifically binds to and inactivates
      cyclin-dependent kinase 4 (CDK4). Its encoding gene (p16/CDKN2) maps to
      chromosome 9p21, a region that undergoes frequent loss of heterozygosity in a
      variety of human tumors. We have analyzed the p16/CDKN2 gene and its expression
      in a series of primary glioma samples. Although homozygous deletion or mutation
      of the p16/CDKN2 gene was uncommon in this series and P16INK4 protein was
      detectable in all grade II tumors, it was present in only 50% of grade III and
      grade IV samples. Conversely, in some grade IV tumors that level of P16INK4
      protein was elevated; in these cases, its target, CDK4, was amplified and
      overexpressed. These results suggest: (a) the involvement of P16INK4 in glioma
      progression; (b) that mechanisms other than mutation or deletion can down
      regulate expression of the p16/CDKN2 gene; and (c) that the balance between CDK4
      and its cognate inhibitor, P16INK4, may confer a cell growth advantage and
      facilitate tumor progression.

PMID- 7728765
TI  - Activation state-specific monoclonal antibody detects tyrosine phosphorylated
      p185neu/erbB-2 in a subset of human breast tumors overexpressing this receptor.
AB  - Amplification of the neu/erbB-2/HER-2 gene and/or overexpression of its receptor
      tyrosine kinase product, p185neu/erbB-2 (p185), occurs in 15-40% of primary human
      breast tumors and is variably correlated with poor patient prognosis. Variability
      in predictive accuracy likely results from activation of p185 by agonist(s) in
      only a subset of tumors in which it is overexpressed, which may greatly affect
      outcomes. As a first step toward evaluating this hypothesis, we previously
      produced a polyclonal antibody that specifically recognizes the activated,
      tyrosine-phosphorylated forms of p185 and the closely related epidermal growth
      factor receptor (L. Bangalore et al., Proc. Natl. Acad. Sci. USA, 89: 11637
      11641, 1992). We now describe the production of a mAb, PN2A, that specifically
      recognizes tyrosine-phosphorylated p185 and bears no cross-reactivity with
      closely related receptors. Furthermore, we demonstrate its reactivity in
      immunohistochemical staining of paraffin-embedded, formalin-fixed tumor samples.
      In a series of five p185-overexpressing human tumors examined thus far, PN2A
      reactivity was detected in two, indicating that p185 is phosphorylated and hence
      actively signaling in a subset. This reagent will facilitate both clinical and
      research analyses of p185 activity. Furthermore, this work serves as a prototype
      for similar analyses of other tyrosine phosphoproteins.

PMID- 7728766
TI  - Met proto-oncogene product is overexpressed in tumors of p53-deficient mice and
      tumors of Li-Fraumeni patients.
AB  - Inappropriate expression of Met, the receptor for hepatocyte growth
      factor/scatter factor, has been implicated in sarcomagenesis via an autocrine
      mechanism. Sarcomas occur at high frequency in individuals with Li-Fraumeni
      syndrome as well as in p53-deficient mice. Here we show that these tumors express
      high levels of Met. Moreover, late passage fibroblast cell lines established from
      p53-deficient animals overexpress Met and can be tumorigenic in athymic nude
      mice, suggesting that progression occurs in vitro. The tumor explants display
      increased hepatocyte growth factor/scatter factor expression and Met turnover,
      indicating that autocrine Met activation contributes to tumor progression. Thus,
      the loss of wild-type p53 appears to greatly enhance the opportunity for
      inappropriate Met expression. Loss of p53 function does not by itself cause
      transformation, but inappropriate Met expression may be an important factor in
      sarcomagenesis.

PMID- 7728767
TI  - Accumulation of genetic abnormalities during neoplastic progression in Barrett's
      esophagus.
AB  - Sex chromosome status, ploidy, and proliferation rate were evaluated in archival
      material of 73 Barrett's esophagus patients (48 males and 25 females). Diagnosis
      in esophageal mucosa samples ranged from intestinal metaplasia with no dysplasia
      to invasive esophageal adenocarcinoma; also, four lymph node metastases were
      studied. Chromosomal and ploidy aberrations were determined by in situ
      hybridization with repetitive DNA probes specific for chromosomes Y, X, and 1.
      Proliferation index (Ki-67 protein expression) was assessed by
      immunohistochemistry. Proliferation rate was elevated in all stages of dysplasia
      and in the adenocarcinomas. Aneuploidy (hyperdiploidy) and loss of the Y
      chromosome correlated with the advancing stages toward neoplasia (P < 0.001) and
      reached high prevalences (70-100%) in high-grade dysplasia and adenocarcinoma.
      Abnormalities of the X chromosome were not seen. These data suggest that in
      Barrett's esophagus, genetic perturbations may be generated in relation to a high
      proliferation rate.

PMID- 7728768
TI  - Two isotypes of murine nm23/nucleoside diphosphate kinase, nm23-M1 and nm23-M2,
      are involved in metastatic suppression of a murine melanoma line.
AB  - A series of sublines of a murine melanoma B16 of C57BL/6 origin were established
      and examined regarding their metastatic capacity and expression of nm23. The
      number of pulmonary metastases developed by these sublines was inversely
      correlated with the expression of two isotypes of nm23, nm23-M1 and nm23-M2. The
      cDNAs of nm23-M1, nm23-M2, and a combination of both were transfected into the
      highly metastatic melanoma subline FE7, with low nm23 expression. FE7
      transfectants of any of these cDNAs expressed transfected genes, and their
      metastatic capacity was suppressed when compared with parental FE7 or FE7
      transfected with a control neo gene. These cell lines, however, did not change in
      terms of in vitro growth in the presence of 3 or 10% fetal bovine serum and in
      vivo growth when injected s.c. into C57BL/6-nu/nu mice. Similar experiments were
      also performed using FE7 transfectants of human nm23 genes. Transfectants of nm23
      H1, nm23-H2, and their combination did not present altered metastatic potential.
      These findings indicated that two murine isotypes of nm23 but not those of humans
      are intimately related with the suppression of metastasis in the murine body.

PMID- 7728769
TI  - Rapamycin enhances apoptosis and increases sensitivity to cisplatin in vitro.
AB  - Apoptosis can be regulated in a number of different systems by the actions of
      cytokines. Rapamycin has been shown to exert its effects on growth factor-induced
      cell proliferation, at least in part, by blocking the activation of the p70 S6
      kinase and thus preventing the downstream signaling process, such as the
      activation of the members of the cdk family. To determine whether this pathway
      plays a role in the regulation of apoptosis, we assessed the effect of rapamycin
      on apoptosis induced by interleukin 2 deprivation in murine T-cell lines, by T
      cell receptor ligation in a murine T-cell hybridoma, by enforced c-myc expression
      in murine fibroblasts, and by corticosteroids in murine T-lymphoma cell lines.
      Although rapamycin did not induce apoptosis on its own, rapamycin augmented
      apoptosis in each of the cell lines used as indicated by increased genomic DNA
      fragmentation, decreased cell viability, and characteristic apoptotic changes in
      morphology. These results suggest that a signal transduction pathway(s) inhibited
      by rapamycin plays an important role in the susceptibility of cells to apoptosis.
      Many chemotherapeutic agents kill cancer cells through the induction of
      apoptosis. Strikingly, rapamycin increased the ability of the alkylating agent,
      cisplatin, to induce apoptosis in the human promyelocytic leukemia cell line HL
      60 and the human ovarian cancer cell line SKOV3. These data suggest that a signal
      transduction pathway, likely related to p70 S6 kinase, inhibited by rapamycin may
      be an important component of the pathway which prevents cell death in many cell
      lineages and also indicate that rapamycin has the potential to augment the
      efficacy of selected anticancer therapies.

PMID- 7728770
TI  - Suramin suppresses hypercalcemia and osteoclastic bone resorption in nude mice
      bearing a human squamous cancer.
AB  - Suramin is a polyanionic agent which has been found to be an effective
      antineoplastic agent against various human tumors including adrenal, renal and
      prostatic cancer, and osteosarcoma. Recently, suramin has been shown to inhibit
      bone resorption in organ cultures of mouse calvarial bones. In the present study,
      we examined the effects of suramin on increased osteoclastic bone resorption and
      hypercalcemia in nude mice bearing a human oral squamous carcinoma. Suramin (1
      mg/mouse/injection) was administered i.p. three times a week for the first 2
      weeks and then once weekly for the next 6 weeks. Blood ionized calcium levels in
      the suramin-treated cancer-bearing group were significantly lower than those in
      the untreated cancer-bearing group. Histological and histomorphometrical
      examination of bones of these animals showed a significant decrease in osteoclast
      numbers in the suramin-treated cancer-bearing animals. Suramin at a dose of 0.1
      mg/mouse/injection was ineffective and 2 mg/mouse/injection was toxic, confirming
      its narrow effective dose. Suramin showed no effects on the growth of this
      squamous cancer. However, suramin markedly inhibited in vivo growth of a rat
      prostatic adenocarcinoma. In mouse marrow cultures, suramin decreased osteoclast
      like cell formation in a dose-dependent manner. Furthermore, suramin also
      inhibited bone resorption in organ cultures of fetal rat long bones and
      resorption pit formation by isolated mature rat osteoclasts. These results show
      that suramin is an effective inhibitor of osteoclastic bone resorption in vitro
      and in vivo and suggest that suramin may be a useful agent in prevention and
      treatment of cancer-induced hypercalcemia. However, our results also suggest that
      for this indication suramin has a confined range of effective dose.

PMID- 7728771
TI  - Dissociation of p34cdc2 complex formation from phosphorylation and histone H1
      kinase activity.
AB  - The cell cycle inhibitor mimosine was used to examine the activation of the
      p34cdc2 protein kinase in S phase of the cell cycle. Addition of mimosine to
      cycling epithelial cells halted cell cycle traverse in S phase, coincident with
      an inhibition of p34cdc2 histone H1 kinase activity. Mimosine treatment did not
      alter p34cdc2 synthesis or turnover; however, overall phosphorylation of p34cdc2
      was decreased to near undetectable levels. Although activity of p34cdc2 was
      inhibited, the ability of the protein to form high molecular weight complexes, a
      phenomenon associated with kinase activation in vivo, was not affected. These
      results indicate that p34cdc2 complex formation can occur in the absence of
      phosphorylation and that phosphorylation of p34cdc2 is then required to activate
      these preformed complexes.

PMID- 7728772
TI  - Effects of lethal irradiation and cyclosporin A treatment on the growth and
      tumoricidal activity of a T cell clone potentially useful in cancer therapy.
AB  - The TALL-104 cell line, originally derived from a patient with T cell leukemia,
      can be maintained indefinitely in culture in the presence of interleukin-2 (IL-2)
      and is endowed with a highly potent major-histocompatibility-complex (MHC)-non
      restricted tumoricidal activity both in vitro and in animal models. The present
      study analyzes in detail the short- and long-term effects of irradiation and
      cyclosporin A (CsA) treatment on the growth and tumoricidal function of this T
      cell clone as compared to polyclonal lymphokine-activated killer (LAK) cell
      preparations from healthy donors. DNA and RNA syntheses by both TALL-104 and LAK
      cells were irreversibly arrested a few hours after irradiation with 40 Gy.
      However, 4-h 51Cr-release assays, performed on different days (day 1 to day 7)
      after irradiation, showed that the cytotoxic efficiency of TALL-104 cells against
      hematopoietic and solid tumor targets was only modestly reduced, whereas that of
      LAK cells was severely inhibited. Moreover, the cytotoxic responses to
      recombinant human IL-2 and IL-12, measured 18 h after irradiation and cytokine
      addition, were normal in the case of TALL-104 cells but were abolished in the
      case of LAK cells. Co-culture of IL-2- or IL-12-preactivated TALL-104 cells with
      a tumor target for 5 days in the absence of cytokines resulted in a lower
      efficiency of lysis, as compared to the non-irradiated effectors, especially if
      the initial stimulus was IL-12. These findings suggest the requirement of
      multiple cytokine stimulation for optimal expression of tumoricidal activity by
      lethally irradiated TALL-104 cells. CsA, while abrogating TALL-104 cell
      proliferation at the low dose of 0.5 microgram/ml, inhibited their cytotoxic
      function marginally only at high doses (100 micrograms/ml). By contrast, CsA
      reduced dose-dependently the cytotoxicity of LAK cells starting at very low doses
      (0.5 microgram/ml). CsA did not impair the ability of TALL-104 and LAK cells to
      produce interferon (IFN) gamma, tumor necrosis factor (TNF) alpha, and
      granulocyte/macrophage-colony-stimulatory factor (GM-CSF) in response to IL-2, IL
      12, or tumor targets. Irradiation reduced drastically IFN gamma production by
      LAK, but not TALL-104 cells; release of TNF alpha and GM-CSF by either type of
      effector was inhibited by 10%-50%, depending on the stimulus. The high resistance
      and immunosuppressive drugs renders tis immortal T cell clone a potentially safe
      and effective reagent for new adoptive-transfer approaches to cancer in MHC
      incompatible recipients.

PMID- 7728773
TI  - Induction of gene expression for immunomodulating cytokines in peripheral blood
      mononuclear cells in response to orally administered PSK, an immunomodulating
      protein-bound polysaccharide.
AB  - The protein-bound polysaccharide extracted from a fungus, PSK, has been used as a
      biological response modifier in the treatment of cancer patients in Japan for
      over 16 years. The administration of PSK to tumor-bearing rodents inhibited tumor
      growth and modulated immune responses. Recently, an in vitro study has revealed
      that PSK is a strong inducer of cytokine gene expression and production in human
      peripheral blood mononuclear cells (PBMC). To establish whether PSK has cytokine
      inducing activities in vivo, we have orally administered PSK (1 g, the clinical
      dose) to 12 healthy volunteers and 9 gastric cancer patients who had undergone
      gastrectomy, and assessed the gene expression for cytokines in PBMC of each
      subject. As determined by the reverse-transcribed polymerase chain reaction
      method, the induction of gene expression for both tumor necrosis factor alpha and
      interleukin-8 (IL-8) was detected in PBMC from 5 of the 12 healthy volunteers
      (42%) and 4 of the 9 patients (44%). Furthermore, the concentration of serum IL-8
      was elevated in 5 healthy volunteers given PSK orally, who had shown induction of
      IL-8 gene expression, as detected by enzyme-linked immunosorbent assay. These
      findings indicate that responsiveness of PBMC to PSK, in terms of gene expression
      and production of cytokines, varies among individuals. Thus, when using PSK to
      treat cancer patients, it seems advisable to select patients on the basis of
      their responsiveness to PSK. We speculate that the cytokines induced by PSK might
      mediate the immunoenhancing action of this agent in vivo.

PMID- 7728774
TI  - Combination of highly purified human leukocyte interferon alpha and 13-cis
      retinoic acid for the treatment of metastatic melanoma.
AB  - The effect of 13-cis-retinoic acid and highly purified human leukocyte interferon
      alpha (Alphaferon) therapy for metastatic melanoma was studied. A group of 17
      patients with disseminated malignant melanoma were treated over a 6-month period.
      They received 60 mg 13-cis-retinoic acid/day continuously and ten cycles of
      interferon alpha (IFN alpha). IFN was administered by subcutaneous injection, at
      a daily dose of 6 x 10(6) IU Alphaferon. The 5-day treatment period was followed
      by an IFN-free interval of 2 weeks. We were able to observe an overall response
      rate of 30% with 12% complete responses (2 out of 17 patients). Sites of response
      included the skin, lung, liver and lymph nodes. All responses have now lasted
      over 6 months. Therapy was generally well tolerated and could be performed on an
      outpatient basis. Side-effects of this combination therapy did not exceed the
      established side-effects of the two substances. We also studied 2'-5'
      oligoadenylate synthetase, beta 2-microglobulin and neopterin levels during the
      whole treatment course. All patients were within the normal range before
      treatment and a sharp rise occurred during each IFN cycle. The maximum being
      observed 24 h after the third injection. This indicates a high biological
      activity of IFN alpha administered cyclically during the whole treatment course.
      This finding also corresponds well with the absence of neutralizing antibodies
      before and after the whole treatment period.

PMID- 7728775
TI  - CD8+ T cells from a patient with colon carcinoma, specific for a mutant p21-Ras
      derived peptide (Gly13-->Asp), are cytotoxic towards a carcinoma cell line
      harbouring the same mutation.
AB  - Several T lymphocyte clones (TLC), specific for a p21-Ras-derived peptide
      expressing a Gly13-->Asp mutation and of the CD8+ subtype, were generated from
      peripheral blood of a colon carcinoma patient. The TLC exerted cytotoxicity
      against an interferon-gamma (IFN gamma)-pretreated colon carcinoma cell line,
      HCT116, which harbours the Gly13-->Asp mutation and shares both HLA-A2 and HLA
      B12(44) with the patient. This cytotoxic effect could be blocked by a monoclonal
      antibody (mAb) against CD8 molecules, as well as with a mAb against HLA class I
      molecules and a polyclonal antiserum against HLA-B12, identifying B12(44) as the
      antigen-presenting molecule. In growth-inhibition experiments, the growth of both
      IFN gamma-pretreated and untreated target cells were strongly inhibited by the
      presence of the CD8+ TLC. Together these data indicate that human cancer cells
      harbouring a spontaneous ras mutation can process aberrant p21 Ras and express
      peptide/HLA-class-I complexes on their surface in sufficient density to be
      recognized by Ras-specific cytotoxic T lymphocytes.

PMID- 7728776
TI  - The antitumor effect of tumor-draining lymph node cells activated by both anti
      CD3 monoclonal antibody and activated B cells as costimulatory-signal-providing
      cells.
AB  - To establish an efficient cell-culture system for adoptive immunotherapy, we
      attempted to use lipopolysaccharide(LPS)-activated B cells (LPS blasts) as
      costimulatory-signal-providing cells in the in vitro induction of antitumor
      effector cells. Both normal and tumor-draining lymph node cells were efficiently
      activated by both anti-CD3 monoclonal antibody (mAb) and LPS blasts, and
      subsequently expanded by a low dose of interleukin-2 (IL-2; anti-CD3 mAb and LPS
      blasts/IL-2). The expanded cells were predominantly CD8+ T cells and showed a low
      level of tumor-specific cytotoxic T lymphocyte (CTL) activity. The adoptive
      transfer of B16-melanoma-draining lymph node cells expanded by anti-CD3 mAb and
      LPS blasts/IL-2 showed significant antitumor effect against the established
      metastases of B16 in combination with intraperitoneal injections of IL-2. This
      treatment cured all B16-bearing mice. In addition, these mice also showed tumor
      specific protective immunity against B16 at the rechallenge. Considering that
      activated B cells express several kinds of costimulatory molecules, these
      findings thus indicate an efficacy of costimulation that is derived from
      activated B cells for the in vitro induction of tumor-specific CTL, in co
      operation with anti-CD3 mAb. The culture system presented here may thus be
      therapeutically useful, providing potent effectors for adoptive immunotherapy
      against various types of cancer.

PMID- 7728777
TI  - Bispecific antibodies retarget murine T cell cytotoxicity against syngeneic
      breast cancer in vitro and in vivo.
AB  - Bispecific antibodies with specificity for CD3 and a tumor antigen can redirect
      cytolytic T cells to kill tumor targets, regardless of their natural specificity.
      To assess the clinical potential of bispecific antibodies for treatment of human
      cancers we have, in the present study, adapted a totally synergeic mouse model to
      the targeting of mouse T cells against mouse tumors in immunocompetent mice. We
      show that gp52 of the mouse mammary tumor virus (MTV) can serve as a tumor
      specific antigen for redirected cellular cytotoxicity. Chemically crosslinked and
      genetically engineered bispecific antibodies with specificities for gp52 and
      murine CD3 epsilon-chain induced activated mouse T cells to specifically lyse
      mouse mammary tumor cells from cultured lines and primary tumors from C3H-MTV+
      mice. Retargeted T cells also blocked the growth of mammary tumors in vitro as
      well as their growth in syngeneic mice. These findings identify murine MTV
      induced mammary adenocarcinomas as a solid-tumor, animal model for retargeting T
      cells with bispecific antibodies against syngeneic breast cancer.

PMID- 7728778
TI  - Construction and characterization of the chimeric monoclonal antibody E48 for
      therapy of head and neck cancer.
AB  - Data from an ongoing clinical radioimmunoscintigraphy trial indicate that 99mTc
      labeled monoclonal antibody (mAb) E48 is highly capable of selectively targeting
      squamous cell carcinoma of the head and neck (HNSCC). The percentage of the
      injected dose per gram of tumor tissue was found to be high, rendering mAb E48 a
      promising candidate mAb for therapeutic purposes. We now describe the
      construction of a chimeric (mouse/human) mAb E48 by recombinant DNA technology.
      The genes encoding the variable domains of the heavy and light chain were cloned
      and ligated into expression vectors containing the human gamma 1 heavy-chain gene
      and the human kappa light-chain gene respectively. Biological properties of the
      resulting chimeric mAb E48 were compared to the murine form in vitro and in vivo.
      The reactivities of chimeric (c)mAb and murine (m)mAb E48 with HNSCC, as assessed
      by immunohistochemical staining as well as immuno-blotting were shown to be
      similar. The affinity constant appeared to be 0.9 x 10(10) M-1 and 1.6 x 10(10) M
      1 for the mmAb and cmAb respectively. The biodistribution of both antibodies was
      tested by simultaneous injection into nude mice bearing human HNSCC xenografts.
      cmAb E48 was found to be cleared more rapidly from the blood than mmAb E48,
      resulting in a 30% lower tumor uptake but similar tumor to non-tumor ratios, 3
      days after injection. Moreover, it was shown that cmAb E48 is highly capable of
      lysing HNSCC targets in ADCC assays in vitro, whereas the mmAb appeared to be
      almost inactive. These data indicate that cmAb E48 has potential as a targeting
      agent for the eradication of HNSCC in man.

PMID- 7728779
TI  - Serum antibody responses against human papillomavirus in relation to tumor
      characteristics, response to treatment, and survival in carcinoma of the uterine
      cervix.
AB  - To investigate whether the serum antibody responses to human papillomavirus (HPV)
      in cervical carcinoma were related to the clinical and histopathological features
      of the tumors and how the antibody responses were affected by treatment,
      pretreatment serum samples from 66 patients with carcinoma of the cervix were
      studied for the presence of IgA or IgG responses against six defined HPV
      epitopes. Posttreatment serum samples were drawn from the same patients 2-24
      months after initiation of treatment. There was no significant correlation
      between pretreatment level of any of the investigated antibodies and clinical
      stage or differentiation of tumor. For the IgA responses to the epitopes 245:16
      and 245:18 in the E2 protein there was a significant correlation between an
      increased pretreatment antibody level and a shortened survival. A high
      pretreatment value of IgA against 245:16 was also associated with the absence of
      any complete response after therapy. The antibody levels declined dramatically
      after therapy for most of the antigens studied. However, this decline was seen
      both among the 53 patients with complete remission and among the 13 patients with
      remaining or progressive disease. Thus, the investigated serological responses
      were not useful as tumor markers, since patients with progressive, late-stage
      disease may fail to mount an antibody response to these proteins. However,
      pretreatment levels of the serological responses to the HPV epitopes 245:16 and
      245:18 were associated with prognosis in cervical cancer.

PMID- 7728780
TI  - Examination of lymphokines induced in mice following immunization with
      recombinant simian virus 40 large tumor antigen.
AB  - Baculovirus-derived recombinant simian virus 40 (SV40) large tumor antigen (T-Ag)
      was used to immunize BALB/c mice to examine the lymphokines produced following
      immunization. Specifically, we examined production of interleukin-2 (IL-2), IL-4,
      IL-5 and interferon gamma (IFN gamma) from immune lymphocytes cultured with
      decreasing concentrations of recombinant SV40 T-Ag. We identified elevated levels
      of IFN gamma and IL-2 by enzyme-linked immunosorbent assay and a murine CTLL-2
      proliferation bioassay respectively. We were unable to detect either IL-4 or IL
      5. These data indicate the previously reported tumor immunity induced by
      recombinant SV40 T-Ag immunization most likely reflects a TH1-like immune
      response based on the in vitro production of both IFN gamma and IL-2 by immune
      lymphocytes.

PMID- 7728781
TI  - The challenge of chagasic cardiomyopathy. The pathologic roles of autonomic
      abnormalities, autoimmune mechanisms and microvascular changes, and therapeutic
      implications.
AB  - The evidence provided by both human and animal studies on chronic Chagas' heart
      disease suggests that the cardiomyopathy occurs as a consequence of several
      physiopathological processes occurring after infection interacting with
      unidentified host factors. The development of the chronic fibrosing myocarditis
      is related to progressive and additive focal cellular necrosis, and associated
      inflammatory lymphomononuclear infiltrate and reactive and reparative myocardial
      fibrosis and surrounding myocyte hypertrophy. These processes may be initiated
      and perpetuated by alterations in the myocardial microcirculation and by
      autoimmune factors. The autonomic impairment and/or the chronic fibrosing
      myocarditis and the left ventricular dysfunction could act as factors
      predisposing one to an increased risk of sudden cardiac death.

PMID- 7728782
TI  - Cardiac disease and nonorganic chest pain: factors leading to disability.
AB  - Research has shown that many chest pain patients, without coronary artery
      disease, may suffer from panic disorder, hypochondriasis, depression, and/or
      multiple phobias. Some patients with coronary artery disease may also suffer from
      these disorders and are often unable to return to previous activity. In spite of
      good prognosis for longevity and acceptable exercise test results, a large
      proportion of these patients continue to be disabled by chest pain and/or chronic
      cardiac fears and demand constant medical attention. This study examined the
      psychiatric and behavioral symptomatology that differentiated four groups of
      patients experiencing chest pain: the able (active/working patient) with and
      without coronary artery disease, as determined by exercise thallium-201 studies,
      and the disabled (inactive/nonworking patient) with and without coronary artery
      disease. The results of the study indicated that the inactive patients, both with
      and without heart disease, suffered from a host of debilitating psychiatric
      conditions.

PMID- 7728783
TI  - Lack of a thrombotic tendency in patients with acute myocardial infarction and
      angiographically normal coronary arteries.
AB  - The hematological profile of 12 patients with acute myocardial infarction and
      normal coronary arteriographic findings was compared to that of 8 patients with
      acute myocardial infarction associated with obstructive coronary artery disease,
      and of 12 patients with no evidence of myocardial infarction and normal coronary
      arteriographic and left ventriculographic findings who served as control. There
      were no significant differences in the hematological profile among the 3 groups,
      suggesting lack of a thrombotic tendency in patients with acute myocardial
      infarction and normal coronary arteriographic findings.

PMID- 7728784
TI  - Diagnostic accuracy of physicians for identifying patients with acute myocardial
      infarction without an electrocardiogram. Experiences from the TEAHAT Trial.
AB  - AIM: To determine the diagnostic accuracy of physicians for identifying patients
      with acute myocardial infarction (AMI) without an electrocardiogram (ECG).
      PATIENTS: All patients in Goteborg with suspected AMI below 75 years of age who
      called for an ambulance or came directly to one of the two city hospitals with a
      delay time of less than 2 h 45 min from the start of symptoms. METHODS: As part
      of the TEAHAT study (comparing rt-PA and placebo in AMI), we asked physicians to
      judge on a 1-5 scale (1 = no suspicion; 5 = convinced) how strong their suspicion
      of AMI was prior to interpreting the ECG. RESULTS: Among patients evaluated
      outside hospital with 4 or 5 on the scale, i.e. either a strong suspicion of AMI
      or the physician felt convinced about the diagnosis, 45% had ST elevation and 48%
      developed AMI during the first 3 days in hospital. The corresponding values for
      patients evaluated in hospital were 67 and 70%, respectively. CONCLUSION: We
      found that physicians could not accurately distinguish patients with AMI from
      those without based on clinical criteria without the help of an ECG.

PMID- 7728785
TI  - Effect of atrial and ventricular activation interval on hemodynamics during
      atrioventricular and ventriculoatrial pacing: determination from pressure-volume
      loops in dogs.
AB  - To determine the effect of relative timing of atrial and ventricular activation
      on hemodynamic indices, we evaluated pressure-volume loops during pacing at 160
      beats/min with various atrioventricular intervals in dogs. End-systolic pressure,
      end-diastolic volume, and stroke volume were reduced during pacing at
      atrioventricular intervals of 0 ms, compared with 80 ms. These changes were more
      significant during pacing at atrioventricular intervals of -50 and -100 ms than
      at 0 ms. During tachycardia, the abnormal timing of atrial contraction leads to
      unfavorable hemodynamic change and the degree of the changes are determined by
      the ventriculoatrial activation interval.

PMID- 7728787
TI  - Cilazapril with adjunctive hydrochlorothiazide. Analysis of safety and efficacy
      in hypertensive patients not responding to cilazapril alone.
AB  - Experience is presented from clinical trials conducted during the development of
      cilazapril (CLZ) for the treatment of hypertension, in which hydrochlorothiazide
      (HCTZ) was added to the treatment regimen in patients whose blood pressures did
      not normalize [sitting diastolic blood pressure (SDBP) < or = 90 mm Hg] in
      response to CLZ alone. In 906 mild-to-moderate hypertensives (SDBP = 95-114 mm
      Hg), adjunct therapy with 12.5-25 mg HCTZ added to 5 mg CLZ provided an
      additional 3-9 mm Hg reduction in SDBP and increased the normalization rate by 13
      27%. Additional efficacy of the combination occurred without any compromise in
      safety (assessed in 1,189 mild-to-moderate and 99 severe hypertensives and in 9
      normal healthy volunteers). Long-term treatment with CLZ and adjunctive HCTZ was
      well tolerated. The majority of clinical and laboratory adverse events were mild
      to moderate and not serious; only 5.7% of the mild-to-moderate hypertensives and
      3.3% of the severe hypertensives withdrew from the studies due to adverse events
      and/or intercurrent illness. Therefore, given that the addition of HCTZ to CLZ
      appears to improve efficacy with no additional safety risk, combining CLZ with
      HCTZ appears to be a rational clinical choice for patients whose blood pressures
      do not normalize on CLZ monotherapy.

PMID- 7728786
TI  - Hemodynamic effects and pharmacokinetics of oral milrinone for short-term support
      in acute heart failure.
AB  - The present study evaluated the acute hemodynamic response, effects on subjective
      symptoms and physical findings, and the pharmacokinetics of a single oral dose
      (2.5, 5, or 10 mg) of milrinone in 31 patients with acute or decompensated heart
      failure. We found a significant increase in cardiac index (29, 31, and 29%,
      respectively, p < 0.01) and a significant decrease in pulmonary capillary wedge
      pressure (39, 43, and 47%, respectively, p < 0.01) accompanied with improvement
      in subjective symptoms and physical findings. These hemodynamic effects persisted
      for 4-8 h after each dosage of milrinone. Dose-dependent hemodynamic response was
      observed between the drug concentration and percent maximum changes in pulmonary
      capillary wedge pressure (peak milrinone concentration, 2.5 mg: 99.99 +/- 57.49,
      5 mg: 187.11 +/- 71.37, and 10 mg: 300.94 +/- 158.5 ng/ml). The finding, together
      with results of the Prospective Randomized Milrinone Survival Evaluation
      (PROMISE) study, suggests lower dose of milrinone will be useful for the short
      term inodilator support in patients with acute or decompensated heart failure.

PMID- 7728788
TI  - Short- and long-term prognostic implications of in-hospital postinfarction
      arrhythmias. DAVIT II Study Group.
AB  - The purpose of the present study was to evaluate, in patients surviving the first
      postinfarction week, the short- and long-term prognostic implications of
      arrhythmias, and their relation to easily obtained anamnestic and clinical
      parameters presented during hospitalisation. The study consisted of 897 placebo
      treated patients of the Danish Verapamil Infarction Trial II (DAVIT II). In
      patients with and without supraventricular tachycardia mortality within 2 months
      was 9.2 and 3.7% (p = 0.004), respectively. By multivariate analysis
      supraventricular tachycardia independently predicted mortality within 2 months.
      Mortality within 5 years was predicted by the presence of supraventricular
      tachycardia, atrial fibrillation, advanced atrioventricular block, sinoatrial
      block, and of the combined arrhythmic parameter, i.e. ventricular and/or atrial
      fibrillation and/or advanced atrioventricular block. When easily obtained and
      assessed anamnestic and clinical parameters were included in a multivariate
      analysis, the presence of supraventricular tachycardia alone gave independent
      prognostic information on long-term mortality.

PMID- 7728789
TI  - Prognosis in patients with acute chest pain in relation to chronic beta-blocker
      treatment prior to admission to hospital.
AB  - We evaluated the prognosis among consecutive patients hospitalized for acute
      chest pain or other symptoms suggestive of acute myocardial infarction (AMI) in
      relation to whether they were on chronic treatment with beta-blockers at onset of
      symptoms or not. In all, 3,504 patients were included in the analyses, of whom
      936 (27%) were on chronic beta-blockade. Of the patients on beta-blockade, 25%
      developed AMI as compared with 21% of the remaining patients (p > 0.2). The
      mortality during the first 28 days was 7% in patients on chronic beta-blockade as
      compared with 5% in those not on beta-blockade (p > 0.2). When correcting for
      differences at baseline, chronic treatment with beta-blockers did not
      significantly influence the outcome.

PMID- 7728790
TI  - Prognostic information from on-line vectorcardiography in unstable angina
      pectoris.
AB  - The prognostic information from 24-hour monitoring with on-line
      vectorcardiography (VCG) was assessed in 100 patients with a clinical diagnosis
      of unstable angina pectoris. ST change vector magnitude, ST vector magnitude and
      QRS vector difference were monitored. During a follow-up period of 343 +/- 77
      days, 7 patients died from cardiac causes and 8 patients had a nonfatal
      myocardial infarction (MI). Thirty patients were readmitted for unstable angina
      pectoris and 36 were revascularized because of medical refractory angina.
      Univariate predictors of cardiac death or nonfatal MI included greater age, rest
      pain during hospitalization, previous MI, diabetes mellitus and high incidence of
      supposedly ischemic transient ST and QRS vector changes. In multivariate
      analysis, a high incidence of transient ST (p < 0.01) and QRS (p < 0.01) vector
      changes provided additional prognostic information beyond that of clinical and
      exercise test data. In conclusion, VCG monitoring during the first 24 h of
      hospitalization for unstable angina pectoris identifies patients with increased
      risk of adverse cardiac events.

PMID- 7728791
TI  - Comparative assessment of right ventricular volumes and ejection fraction by
      thermodilution and magnetic resonance imaging in dilated cardiomyopathy.
AB  - Measurements of right ventricular (RV) ejection fraction (EF) and volumes using a
      new thermodilution technique were compared to serially performed magnetic
      resonance imaging (MRI) in 21 patients with dilated cardiomyopathy. For RVEF (%)
      and RV volume indices (ml/m2) the following correlation coefficients were found:
      RVEF r = 0.82; end-diastolic volume index (EDVI) r = 0.45; end-systolic volume
      index (ESVI) r = 0.65; stroke volume index (SVI) r = 0.61; all p < 0.05. However,
      RVEF by thermodilution was significantly lower (RVEF thermo = 31 +/- 14 vs. RVEF
      MRI = 50 +/- 14, p < 0.01) and RV EDV and ESVI were significantly higher compared
      to MRI, while SVI showed no significant difference. Exclusion of patients with
      atrial fibrillation (n = 8) improved the correlations (RVEF r = 0.94, EDVI r =
      0.77, ESVI r = 0.87, SVI r = 0.65, all p < 0.05), but did not reduce the mean
      difference between both methods.

PMID- 7728792
TI  - Unique spontaneous coronary artery dissection in an elderly woman.
AB  - Spontaneous coronary artery dissection is a rare condition, typically occurring
      in younger women. A 75-year-old woman with this condition, 17 years older than
      previously reported, is described, including her unusual presentation with angina
      rather than infarct. The 112 previously reported cases are summarized and
      treatment options discussed.

PMID- 7728793
TI  - Exacerbated tamponade: deterioration of cardiac function by lowering excessive
      arterial pressure in hypertensive cardiac tamponade.
AB  - Patients with cardiac tamponade usually have significant hypotension;
      hypertension is rare. Before administering any medication during tamponade one
      must consider the complex physiology and compensatory mechanisms of cardiac
      compression [1]. We observed both an accentuation of pulsus paradoxus and
      retrospectively recognized fluctuations of left-ventricular function after
      progressively rising arterial blood pressure had been lowered.

PMID- 7728794
TI  - Transient myocardial ischemia after myocardial infarction.
AB  - Ambulatory ST-segment monitoring is a relatively new device in the evaluation of
      myocardial ischemia. The method is unique in allowing us to continuously examine
      the patient over an extended period of time in a changing environmental milieu.
      In survivors of acute myocardial infarction the prevalence of ambulatory or
      transient myocardial ischemia is lower than in patients with chronic, stable
      coronary artery disease. A greater proportion of ischemic episodes, however, are
      silent than in other subgroups with ischemic heart disease. Early after the
      infarction, transient myocardial ischemia exhibits a circadian variation with a
      peak activity occurring in the late evening hours. Patients with non-Q wave
      infarction have more transient myocardial ischemia, whereas thrombolytic therapy
      seems to result in less residual ischemia. Exercise testing is more sensitive
      than ambulatory monitoring in the detection of postinfarction myocardial
      ischemia. There appears to be a poor association between transient myocardial
      ischemia and severe left ventricular dysfunction. Transient myocardial ischemia
      has been shown to provide prognostic information in different subsets of patients
      with previous myocardial infarction, but there is considerable disagreement about
      how this is expressed in terms of cardiac events. The precise role of
      postinfarction ST-segment monitoring in clinical practice has yet to be
      established.

PMID- 7728795
TI  - Doppler echocardiographic diagnosis and follow-up of acquired pulmonary stenosis
      due to external cardiac compression.
AB  - Mediastinal tumors that cause hemodynamic disturbances by compressing the heart
      are extremely rare. We report the case of a 19-year-old woman who presented right
      ventricular outflow tract obstruction due to a non-Hodgkin lymphoma. The
      diagnosis of this complication and its response to chemotherapy can be accurately
      assessed by transthoracic echocardiography and Doppler.

PMID- 7728796
TI  - Primary cardiac angiosarcoma. A case report.
AB  - A primary cardiac malignancy is a very rare diagnosis. The most prevalent
      malignant cardiac tumors are angiosarcomas. Autopsy specimens, microscopic
      slides, clinical and intraoperative data from a 72-year-old woman referred to our
      hospital with a suspected mediastinal tumor were studied. The patient was
      diagnosed with primary cardiac angiosarcoma by microscopic examination under
      surgery and underwent resection of the tumor, which compressed and obstructed the
      right atrium and ventricle. She was discharged from our hospital after 3 weeks
      and died of right heart failure 2 months after the operation.

PMID- 7728797
TI  - Trapped venous embolus in a patent foramen ovale causing recurrent paradoxical
      embolism.
AB  - The combination of deep venous thrombosis, patent foramen ovale and arterial
      emboli suggests the diagnosis of paradoxical embolism. In these cases, only very
      rarely, a causal relationship between the venous thrombus and the patent foramen
      can be established. An instructive case of trapped venous embolism within the
      foramen ovale is described proving a causal relationship between arterial
      embolism and its venous origin.

PMID- 7728798
TI  - Effect of age on blood pressure response to cigarette smoking.
AB  - The plasma nicotine level and hemodynamic parameters were evaluated after
      cigarette smoking in young (group I, 17 men) and middle-aged habitual smokers
      (group II, 17 men). The amount of increase in plasma nicotine concentration after
      smoking was related to the percent change of mean blood pressure in both groups.
      The total peripheral vascular resistance index (TPRI) increased significantly at
      10 min after smoking and reduced thereafter in group I, whereas the TPRI
      increased till 30 min after in group II. Thus, smoking raised the TPRI for a
      longer time in the middle-aged subjects due to a decrease in aortic elasticity
      with aging.

PMID- 7728799
TI  - Exercise capacity and prognosis in patients with chronic atrial fibrillation.
AB  - To evaluate the response of patients with chronic atrial fibrillation (AF) to
      exercise and to demonstrate if prognosis could be predicted, 200 male patients
      (64 +/- 1 years) with AF were identified retrospectively who underwent resting
      echocardiography and symptom-limited treadmill testing. They were classified by
      underlying disease into three subgroups: hypertension or no underlying disease
      (LONE; n = 102), ischemic heart disease (IHD; n = 45) and history of congestive
      heart failure or valvular disease (CHF-VD; n = 53). Maximal exercise capacities
      for LONE, IHD and CHF-VD were (mean +/- 1 SEM) 8.0 +/- 0.3, 6.4 +/- 0.4 and 6.0
      +/- 0.3 metabolic equivalents, respectively (p < 0.01), and resting left
      ventricular ejection fractions were 61.7 +/- 1.6, 60.1 +/- 2.2 and 49.5 +/- 1.9%,
      respectively (p < 0.01). Stepwise multiple regression analysis demonstrated that,
      except for group classification (R2 = 0.13, p < 0.01), no clinical, exercise or
      morphologic variables could predict exercise capacity. After a mean 39.1-month
      follow-up (range 1-78), 17 of the 200 had died from cardiovascular causes. The
      rate of cardiac death using Kaplan-Meier survival analysis was significantly
      greater in CHF-VD patients (p < 0.01). However, Cox hazard function and Kaplan
      Meier survival analysis demonstrated that neither echocardiographic measurements
      of cardiac size or function at rest, nor exercise or clinical variables were
      significant predictors of outcome. AF patients with a history of CHF and/or VD
      demonstrated a reduced exercise tolerance ad a worse prognosis than those without
      morphologic heart disease or those with IHD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728800
TI  - Gender-dependent variability of signal-averaged electrocardiogram in acromegaly.
AB  - Ventricular late potentials are obtained by signal-averaged surface
      electrocardiography. Late potentials in normal subjects may be influenced by
      physiological elements such as gender, height and body mass index. Considering
      that growth hormone (GH) hypersecretion is able to markedly alter different
      anthropometric variables, we studied the relation between these elements and the
      late potentials of 22 acromegalic patients. Males registered higher absolute QRS
      duration and LAS40 (low-amplitude signal) and, on the opposite, lower RMS40 (root
      mean square) in comparison to females; QRS duration and LAS40 seem to depend,
      however, on the different anthropometric variables, since their normalization
      with height and lean body mass (LBM) abolishes gender-dependent differences. On
      the contrary, the persistence, among males, of lower RMS40 in respect to females
      even after normalization for height, LBM and insulin-like growth factor 1 values
      makes it likely that the latter ECG variable is independent of the anthropometric
      ones and from the disease's activity. Moreover, males appear to be more
      vulnerable to GH heart-harming activity.

PMID- 7728801
TI  - Congestive heart failure in patients with valvular aortic stenosis. A clinical
      and echocardiographic Doppler study.
AB  - The aim of this study was to evaluate echographically anatomic and functional
      features of the left ventricle in adult patients with valvular aortic stenosis
      according to the presence or absence of congestive heart failure and the level of
      ventricular performance. Fifty-six adult patients with moderate-to-severe aortic
      stenosis underwent echocardiographic Doppler examination in order to evaluate
      left ventricular mass and dimensions, systolic function and filling dynamics.
      Twenty-seven patients had no heart failure and were symptomatic for angina (5),
      syncope (4) or were symptom-free (group I); the other 29 had heart failure (group
      II): 16 with normal left ventricular systolic performance (fractional shortening
      > 25%, group IIa) and 13 with systolic dysfunction (fractional shortening < or =
      25%, group IIb). Despite a similar left ventricular mass, compared to group IIa,
      group IIb showed a significant left ventricular dilatation (end-diastolic
      diameter: 61 +/- 6.5 vs. 45.5 +/- 6.1 mm, p < 0.001) and mild or no increase in
      wall thickness (11.5 +/- 1.6 vs. 14.9 +/- 2 mm, p < 0.001). Indices of left
      ventricular filling on Doppler transmitral flow were also significantly different
      between the two groups, with a higher early-to-late filling ratio and a shorter
      deceleration time of early filling in group IIb (2.8 +/- 1.9 vs. 1.2 +/- 0.85, p
      < 0.01, and 122 +/- 66 vs. 190 +/- 87 ms, p < 0.05, respectively), both
      indirectly indicating higher left atrial pressure. Finally, heart failure was
      generally more severe in group IIb patients. In some patients with aortic
      stenosis, symptoms of heart failure may be present despite a normal left
      ventricular systolic function and seem to depend on abnormalities of diastolic
      function. The presence of systolic or isolated diastolic dysfunction appears to
      be related to a different geometric adaptation of the left ventricle to chronic
      pressure overload.

PMID- 7728802
TI  - Evaluation of CK and CK-MB in alcohol abuse subjects with recent heavy
      consumption.
AB  - We analyzed CK and CK-MB levels over 24 h in 15 male subjects admitted for
      alcohol detoxification following recent heavy ingestion. None had clinical or
      electrocardiographic evidence of myocardial ischemia or infarction. The mean 0
      hour serum alcohol level +/- SD was 342 +/- 101 mg/dl. CK levels were measured by
      Kodak Ektachem and Abbott IMx assays, and CK-MB levels were determined by these
      assays and the Hybritech isoenzyme test. In 36% of the patients elevated 0-hour
      CK levels by the IMx and Ektachem assays were observed. The CK levels measured
      every 8 h decreased so that by 24 h CK was elevated in 1 patient by the Ektachem
      assay and in 2 by the IMx assay. Only 1 patient (7%) had an elevated 0-hour CK-MB
      value by two of the three assays, and it is unclear whether the source was
      cardiac or extracardiac. We conclude that: (1) elevated CK levels are common in
      heavy alcohol use patients without evidence of myocardial ischemia; (2) CK values
      over the first 24 h are decremental, not rising and falling as is typical of
      myocardial infarction and (3) current isoenzyme immunoassays eliminate a cardiac
      cause for elevated CK in most of these patients. These findings may assist in the
      evaluation of alcoholic patients with chest pain.

PMID- 7728803
TI  - Value of local electrogram characteristics predicting successful catheter
      ablation of left-versus right-sided accessory atrioventricular pathways by
      radiofrequency current.
AB  - Despite similar guidance by local electrogram criteria, catheter ablation of
      right-sided accessory atrioventricular (AV) pathways by radiofrequency current
      has been less effective than that of left-sided ones. In order to elucidate the
      possible diversities in local electrosignal criteria, we systematically analyzed
      the morphological and timing characteristics of 215 bipolar local electrograms
      from catheter ablation sites of 65 left-sided accessory AV pathways and of 356
      from those of 37 right-sided ones in 92 consecutive patients with Wolff-Parkinson
      White syndrome or AV reentrant tachycardia incorporating concealed accessory AV
      pathways. After stepwise multivariate analysis, we selected the presence of a
      possible accessory pathway potential, local ventricular activation preceding QRS
      complex for 20 ms or more during ventricular insertion mapping, and the local
      retrograde ventriculoatrial (VA) continuity, local retrograde VA interval < or =
      50 ms, electrogram stability (left-sided targets only), retrograde accessory
      pathway potential (right-sided targets only) during atrial insertion mapping, as
      independent local electrogram predictors for successful ablation of left- and
      right-sided accessory AV pathways. Combination of all local electrogram
      predictors could have moderate chance of success (80 and 51%) for the ventricular
      and atrial insertion ablation of left-sided accessory AV pathways, but only low
      probability of success (40% in ventricular insertion ablation) or very low
      sensitivity (12.5% in atrial insertion ablation) for right-sided ones. In
      conclusion, with the present approach, successful catheter ablation of right
      sided accessory AV pathways, compared to left-sided ones, still necessitate a
      breakthrough in the precision mapping and the efficiency of energy delivery.

PMID- 7728804
TI  - Glycosaminoglycan distribution in atherosclerotic saphenous vein grafts.
AB  - Glycosaminoglycan composition of normal saphenous veins and atherosclerotic
      saphenous vein grafts is reported. Dermatan sulfate is the main glycosaminoglycan
      present in both normal saphenous veins and saphenous vein grafts. These tissues
      also contain chondroitin sulfate and heparan sulfate. Although the total amount
      of glycosaminoglycans decreased in the grafts (compared with normal saphenous
      veins), the grafts showed an increase in the relative amounts of dermatan sulfate
      and chondroitin sulfate. Heparan sulfate was decreased, compared with normal
      controls. These findings suggest the involvement of blood vessel
      glycosaminoglycans (not only the arterial glycosaminoglycans) in the process of
      atherosclerosis.

PMID- 7728805
TI  - Clinical significance of S-T segment elevation in lead aVR in anterior myocardial
      infarction. Assessment by thallium-201 exercise scintigraphy.
AB  - The significance of exercise-induced S-T elevation in aVR was studied in 57
      patients with recent anterior infarction and single-vessel disease. S-T elevation
      in aVR was found at peak exercise in 24 patients. Although the initial defect
      area was similar in the groups with and without S-T elevation in aVR, the
      redistribution area was larger in the former group (p < 0.01). When three
      electrocardiographic criteria were used in the multivariate analysis, S-T
      elevation in aVR was the significant variable related to redistribution in the
      anterior wall. Thus, S-T elevation in aVR may indicate ischemia of the anterior
      wall.

PMID- 7728806
TI  - Changes in thyroid hormone parameters after acute myocardial infarction.
AB  - Abnormalities in circulating thyroid hormone levels are very common in systemic
      nonthyroidal illnesses, such as acute myocardial infarction. In this study,
      thyroid parameters were determined in a series of 16 consecutive infarction
      patients treated by thrombolysis. Blood samples were taken before therapy as well
      as 2, 4, 6, 8, 12 and 72 h following admission. Total and free serum thyroxin and
      triiodothyronine decreased and reverse T3 increased significantly showing no
      major variations up to 72 h, whereas thyroid-stimulating hormone values remained
      almost unchanged during the observation period. Subjects with CK-MB levels of
      more than 150 ng/ml (n = 10) revealed similar changes in thyroid parameters in
      comparison to those with lower values (n = 6; NS). Thus, although hormone
      modifications very often occur following acute infarction, thyroid status may not
      serve as a marker for the extent of left ventricular dysfunction in the early
      phase of myocardial infarction.

PMID- 7728807
TI  - Prognostic value of echocardiography compared to other clinical findings.
      Multivariate analysis based on long-term survival in 456 patients.
AB  - The prognostic significance of conventional clinical and echocardiographic data
      in patients referred to echocardiography was retrospectively analyzed. 456
      patients (206 females and 250 males) were studied in the department of cardiology
      in a district hospital. Survival after 3 years was 64%. By multivariate analysis
      five factors contained independent, significant, prognostic information (hazard
      ratios for death are given in parentheses): left ventricular wall motion score
      index (WMI) < or = 1.2 by echocardiography (2.5), status as inpatient (2.1), age
      > 65 years (1.7), clinical heart failure (1.9) and atrial fibrillation (1.5). A
      stepwise multivariate analysis was performed by entering variables into a model
      initially forced to contain information on age, hospitalization status, treatment
      of heart failure and heart rhythm. In this analysis, a poor WMI (< or = 1.2) and
      a dilated right ventricle contained further independent prognostic information.
      In conclusion, among conventional clinical and echocardiographic data, WMI was
      the most powerful predictor of long-term survival, and despite knowledge of major
      clinical features echocardiography provided further prognostic information.

PMID- 7728808
TI  - Clinical predictors of reinfarction among men and women after a first myocardial
      infarction. SPRINT Study Group. Secondary Prevention Reinfarction Israeli
      Nifedipine Trial.
AB  - Independent clinical factors predicting reinfarction in the 1st year following an
      initial myocardial infarction were identified among 900 women and 2,795 men.
      Women were older (65.8 vs. 59.3 years; p < 0.001) but tended to suffer from
      reinfarction at a rate similar to that of men (6.9 vs. 5.6%, p = 0.17).
      Cumulative 1-month, 1- and 5.5-year all-cause mortality following the first
      infarction was higher among women who sustained reinfarction (43, 52 and 74%,
      respectively) than among men (29, 30 and 51%, respectively, p < 0.01 for each).
      Independent clinical predictors for recurrent myocardial infarction among women
      were (adjusted relative odds): peripheral vascular disease (3.2), postinfarction
      angina (2.3), diabetes mellitus (2.2), radiographic evidence of cardiomegaly
      (1.9), anterior location of the first infarction (2.0), congestive heart failure
      (1.8), prior angina (1.6) and age (10 years) increment (1.2). Predictive
      variables for men were: anterior infarct location (1.7), peripheral vascular
      disease (1.6, prior stroke (1.5), prior angina (1.4), systemic hypertension (1.3)
      and age (10 years) increment (1.1). Our data indicate (a) different cardiac risk
      factors for reinfarction among men and women after a first myocardial infarction,
      and (b) a prognostic advantage for men over women following reinfarction.

PMID- 7728809
TI  - Phasic right coronary blood flow in a patient with right ventricular hypertension
      using transesophageal Doppler echocardiography.
AB  - Although phasic right coronary artery blood flow in right ventricular
      hypertension has been studied in animals, reports on human subjects are not
      available. We observed right coronary artery blood flow before and after
      operation in a patient with right ventricular hypertension secondary to atrial
      septal defect using transesophageal Doppler echocardiography. Prior to surgery,
      blood flow was predominantly diastolic in both right and left coronary arteries.
      Reversal of right ventricular hypertension after surgery resulted in a change in
      the pattern of right coronary flow, with doubling of flow during systole.

PMID- 7728810
TI  - Sudden cardiac death in a 20-year-old bodybuilder using anabolic steroids.
AB  - Anabolic steroid use is widespread and has been associated with a variety of
      pathological conditions. The subject of this case is a 20-year-old amateur
      bodybuilder who died of sudden cardiopulmonary arrest. He had no previous medical
      complaints but had a history of anabolic steroid abuse and a hypertrophic heart
      (515 g) at autopsy. This case presentation will discuss the cardiovascular
      effects of these drugs and the possible impact of long-term abuse.

PMID- 7728811
TI  - Multiple saccular aneurysm formation in a patient with bilateral coronary artery
      fistula: a case report and review of the literature.
AB  - We describe a case of bilateral coronary artery fistula originating from the left
      anterior descending and right coronary arteries which showed multiple saccular
      aneurysm formation. Although saccular aneurysm formation in patients with
      bilateral coronary artery fistula is extremely rare, only 3 similar cases having
      been reported before, it shows two distinctive features upon coronary
      angiography: multiplicity and origin in the left fistulous coronary artery.

PMID- 7728812
TI  - Hypertension therapy and risk of coronary heart disease: how do antihypertensives
      affect metabolic factors?
AB  - A recent meta-analysis of hypertension treatment trials demonstrated a marked
      reduction in the incidence of cerebrovascular disease, but a less pronounced
      reduction in coronary heart disease. Treatment consisted mainly of diuretics and
      beta-blockers, and this paper discusses the possible influences of their
      metabolic side effects on coronary risk factors compared with newer agents:
      angiotensin-converting enzyme (ACE) inhibitors, selective alpha 1-adrenoceptor
      inhibitors and calcium channel blockers. Several studies are underway to compare
      the effect of these compounds with diuretics and beta-blockers with respect to
      long-term cardiovascular morbidity and mortality. Until the results of these
      studies are available, young patients (i.e. < 60-65 years) at high risk of
      coronary heart disease, especially patients with the insulin resistance syndrome
      or diabetes mellitus, should in our opinion be treated with ACE-inhibitors,
      selective alpha 1-adrenoceptor inhibitors or calcium channel blockers.

PMID- 7728813
TI  - A reexamination of the hemodynamic effects of digitalis relative to ventricular
      dysfunction.
AB  - The available data suggest that digitalis improves symptoms of a failing heart in
      the presence of sinus rhythm as well as supraventricular arrhythmias. Intravenous
      digitalis administration in patients with chronic heart failure and baseline
      hemodynamic deterioration increases cardiac index and reduces heart rate. These
      beneficial effects are maintained with long-term oral therapy and are comparable
      with those obtained using dobutamine in patients with chronic severe heart
      failure. The addition of digoxin to therapy with vasodilators and diuretics
      confers clinical benefit in patients with moderate to severe heart failure
      symptoms because of systolic ventricular dysfunction. Digoxin effects on
      diastolic function appear to be different in patients with preserved systolic
      function in comparison to patients with overt heart failure and systodiastolic
      dysfunction. In patients with right ventricular dysfunction digoxin does not
      appear to influence hemodynamic measurements unless concomitant left ventricular
      dysfunction is present.

PMID- 7728814
TI  - DentalMac F/X: a multimedia clinical and practice information management computer
      program--Part 2.

PMID- 7728815
TI  - The clinical performance of a new adhesive resin system in class V and IV
      restorations.
AB  - A clinical trial was initiated to examine a new adhesive system introduced for
      dentin and enamel bonding of composite resins. Restorations were placed in
      patients in need of Class V and Class IV restorations. The clinical study was
      designed to examine the adhesive system in restorations involving mostly dentin
      surfaces (Class V) and in a population of restorations mostly involving enamel
      surfaces (Class IV). At the 1-year recall period, the adhesive system had
      demonstrated excellent adhesive qualities in both types of cavities. Initial
      results also showed improvement over previous adhesive systems with regard to
      moisture sensitivity and variation in dentin composition.

PMID- 7728816
TI  - Clinical evaluation of the efficacy and safety of the UltraSonex ultrasonic
      toothbrush: a 30-day study.

PMID- 7728817
TI  - Referrals--the most powerful marketing tool: nine steps to glowing patient
      endorsements.

PMID- 7728818
TI  - Chloral hydrate sedation: a simple technique.
AB  - Chloral hydrate is an oral sedative commonly used in pediatric dentistry when
      providing extensive treatment in the young child. This article reports the
      results of a clinical trial using an orally administered dose of chloral hydrate
      at 75 mg/kg of body weight plus nitrous oxide and oxygen. A method for
      administering the drug that minimizes initial drug expectoration and vomiting is
      also presented. Because a reliable method for delivery of chloral hydrate is
      essential in a study of the ideal effective dose, the authors describe a
      technique that makes this portion of the treatment process as pleasant as
      possible by associating the drug with a product known to be pleasing to most
      children of this age group. The results of the clinical trial of 50 patients
      revealed that 29 children (58%) slept through the entire procedure and 14 (28%)
      of the children presented only mild resistance either during anesthesia and/or
      treatment. If some mild resistance is acceptable to the practitioner then there
      was an approximately 85% success rate. The authors concluded that chloral hydrate
      used at a 75 mg/kg dose and supplemented by nitrous oxide/oxygen is a safe and
      reliably effective sedative for the preschool child.

PMID- 7728819
TI  - A method of prognosticating complete denture outcomes.
AB  - A simple examination instrument (the Edentulous Exam form) was developed to be
      used in a regular and systematic manner to determine outcomes or prognoses for
      the edentulous patient. Factors that can complicate treatment are discussed. When
      a dentist can gather information about what a patient is presenting with, a
      satisfactory outcome or prognosis can be effectively projected before the actual
      treatment commences.

PMID- 7728820
TI  - Vitamin C (ascorbic acid): clinical implications for oral health--a literature
      review.
AB  - This article reviews the chemistry, functions, and toxicity of vitamin C, as well
      as its food sources, recommended daily allowance, and laboratory biochemical
      findings, to help clinicians understand and recognize its systemic and oral
      deficiency manifestations. An understanding of these topics will help the general
      dentist, periodontist, and oral surgeon appropriately prescribe vitamin C for
      their patients.

PMID- 7728821
TI  - Periodontal repair using PerioGlas in nonhuman primates: clinical and histologic
      observations.
AB  - This article describes a new synthetic material for grafting periodontal osseous
      defects. Compared to grafts of similar-sized hydroxyapatite, tricalcium
      phosphate, and unimplanted controls, PerioGlas achieved histologically superior
      repair of surgically created defects in the monkey model. Superior repair was
      noted when evaluating for new bone and the degree of cementum regeneration.
      Epithelial downgrowth appeared to be retarded in the PerioGlas sites and not in
      the other materials. When comparing clinical handling characteristics, PerioGlas
      was found to have excellent packing and manipulative features that were preferred
      by the operators to the other materials. The property of epithelial downgrowth
      inhibition may be significant in the superior regenerative property of PerioGlas.

PMID- 7728822
TI  - Validity of electrical conductance measurements in evaluating the marginal
      integrity of sealant restorations.
AB  - The use of sealants and sealant restorations has increased considerably over the
      past 10 years, and with it increased the problem of detecting secondary caries
      and marginal (micro)leakage. It was the purpose of this study to investigate the
      validity of electrical conductance measurements (ECMs) in diagnosing marginal
      leakage into dentine of sealants and sealant restorations. Ninety extracted
      premolar teeth were divided into three groups. Initial ECMs, denoted 'baseline
      ECMs', were conducted in all three groups by placing the probe tip of an
      Electronic Caries Monitor in the occlusal fissure which was filled with a
      dentifrice. The ECMs were divided by the area, yielding ECM/mm2 values. In group
      A 30 teeth were treated to receive 'nonleaking sealants'. In the 30 teeth of
      group B a narrow groove was cut at the occlusal surface reaching the dentine and
      restored by the application of a sealant without etching of the adjacent enamel
      to create a high probability of marginal leakage. The samples in group C received
      the same treatment as those in group B, but in this group the enamel was etched
      to reduce the probability of marginal leakage. The ECMs subsequently conducted
      were denoted 'sealed/restored ECMs'. Teeth in groups B and C were thermocycled
      700 times (4-67 degrees C) to provoke leakage, after which ECMs were conducted
      (denoted 'ECMs after thermocycling'). The teeth were immersed in fuchsin for 24 h
      and cut along the fissure system to validate marginal leakage. The electrical
      conductance decreased significantly from baseline to the sealed/restored stage in
      all groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728823
TI  - Contact microradiography of dentine under wet conditions to prevent lesion
      shrinkage.
AB  - A considerable shrinkage of dentinal lesions is the result of desiccation of
      dentine sections during contact microradiography. We introduce a simple
      modification which allows the dentine to be wet during the microradiographic
      procedure. The volume stability of both sound and demineralized dentine sections
      microradiographed under wet conditions is compared to sections microradiographed
      while being exposed to the air. Under wet conditions no shrinkage could be
      detected of both sound and demineralized sections. Within 15 min exposure to the
      air, demineralized sections showed their lesion depth to be significantly reduced
      by 21%, resulting in an underestimation of the mineral loss of 44%. No shrinkage
      was observed in the air-dried sound dentine. Especially when high-resolution
      plates are used, which require an extended exposure time, microradiography of
      dentine sections under wet conditions is recommended. In longitudinal de- and
      remineralization studies, the use of water instead of impregnation with low
      volatility liquids is to be preferred because of the possible effects of these
      liquids on the mineralization processes.

PMID- 7728824
TI  - Mineral content of the dentine remaining after chemomechanical caries removal.
AB  - Although the dentine remaining after chemomechanical caries removal appears sound
      by normal clinical criteria, no definitive evidence has yet been obtained to
      confirm that the dentine surface is in fact mineralised. The aim of this study
      was to use backscattered electron (BSE) imaging and electron probe micro-analysis
      (EPMA) to ascertain the level of mineralisation of the dentine remaining in
      cavities prepared by this technique. Carious dentine was removed from carious
      lesions by means of N-monochloro-DL-2-aminobutyric acid (NMAB) or NMAB containing
      2 mol/l urea. Sections of teeth in which caries removal was complete by normal
      clinical criteria were examined by EPMA and BSE. Dentine adjacent to the pulp was
      found to be less mineralised than the surrounding dentine. Although the
      superficial layer of dentine remaining on the cavity floors frequently appeared
      to have a slightly reduced mineral content, the results clearly indicated that
      there was no significant difference between this dentine and the underlying sound
      dentine.

PMID- 7728825
TI  - The diameter of dentinal tubules in human coronal dentine after demineralization
      and air drying. A combined light microscopy and SEM study.
AB  - The diameter of dentinal tubules after demineralization and/or air drying has
      been quantified using light microscopy and scanning electron microscopy (SEM).
      The tubule diameter was assessed at a distance of about 1.5 mm (range 1.0-2.0 mm)
      from the pulp. Tubule diameter was measured in the wet state, after 10-min and 12
      hour air drying as well as after critical point drying (CO2) by SEM. The results
      show that drying effects on tubule diameter are small in sound tissue, but are
      sizeable in demineralized dentine. Comparing light microscopic (wet) and SEM
      observations show that the differences in tubule diameter are small for sound but
      substantial for demineralized dentine. An important result is that in the wet
      state the diameters of the tubules (being 1.3 +/- 0.2 microns in sound dentine)
      are 2.5 +/- 0.3, 2.2 +/- 0.3 and 1.7 +/- 0.2 microns after 1, 2 and 3 weeks of
      demineralization, respectively. The decreased tubule diameter with increasing
      demineralization may be important for permeability and transport phenomena in
      dentine caries and presumably in hypersensitivity.

PMID- 7728826
TI  - Structure of artificial enamel lesions after topical applications of high
      concentration sodium fluoride solution in vitro.
AB  - A three-layer structure, including a columnar layer (CL), a buffer layer, and
      unaffected intact enamel, was successively formed from the outer to the inner
      part of artificial enamel lesions (AEL) by topical applications of a high
      concentration acidic sodium fluoride solution (10,000 ppm, pH 5.6) in vitro. The
      AEL was produced in bovine enamel that was decalcified for 5 days in a lactic
      acid gel system. The morphological observations by using scanning electron
      microscopy showed that the CL was made of columnar deposits of small globules
      about 0.5 microns in diameter. It was observed for the first time that small
      globules filled the demineralized interprismatic regions in the buffer layer. The
      unaffected intact enamel was protected from further demineralization under the
      acidic condition. Structure and composition of the CL were investigated by using
      X-ray diffraction and X-ray photoelectron spectroscopy. In the CL the atomic
      ratio was Ca:P = 12.6 and Ca:F = 0.75, and the small globules were mainly a
      mixture of polycrystalline calcium fluoride and hydroxyapatite. For comparison,
      the sound enamel and the AEL attained by applications of 0 and 100 ppm acidic
      sodium fluoride solutions (pH 5.6) were also investigated. The formation
      mechanism of the three-layer structure and the related cariostatic effects are
      discussed.

PMID- 7728827
TI  - Stoichiometry of fluoride release from fluorhydroxyapatite during acid
      dissolution.
AB  - Release of F from fluorhydroxyapatite (FHAp) during acid dissolution was studied
      to validate the use of this mineral as a plaque reservoir of F. FHAp minerals
      having a wide range of F concentrations were synthesised by aqueous
      precipitation, and samples repeatedly exposed to 50 mM lactic acid solution, pH
      4.5, or similar lactic/acetic/formic acid mixtures, until dissolution was
      complete. While the Ca/P ratio in solution remained relatively constant and close
      to the ratio in the solid, the solution F/Ca ratio invariably changed during
      dissolution. During initial stages the F/Ca solution ratio was lower than in the
      solid but rose to reach a plateau higher than in the solid as dissolution
      progressed, an effect that was more pronounced with low-F FHAp. With these
      minerals the plateau F/Ca level never reached 0.2, suggesting that a F-enriched
      FHAp rather than pure fluorapatite precipitates during dissolution. It is
      concluded that a high-F FHAp mineral would best serve as an apatitic plaque
      reservoir of F.

PMID- 7728828
TI  - Dental enamel opacities in three groups with varying levels of fluoride in their
      drinking water.
AB  - The aim of this study was to compare the prevalence of enamel defects in three
      groups with different levels of fluoride in their water supplies. These data,
      collected using a reproducible method, will form the baseline for ongoing studies
      on the prevalence of enamel defects. The overall prevalence of enamel defects was
      similar in all three groups. However, for individual categories of defects
      differences were found. The prevalence of demarcated opacities was highest in the
      group with the lowest level of fluoride in the drinking water. The prevalence of
      hypomineralised enamel defects (TF index) increased with increasing levels of
      fluoride in the drinking water. However, the number of teeth affected by these
      enamel defects and their severity did not follow the dose-response relationship
      expected from the fluoride levels in the drinking water. Associations between
      both the frequency of tooth brushing and the age tooth brushing was commenced and
      hypomineralised enamel defects were identified.

PMID- 7728829
TI  - Effects of sodium bicarbonate dentifrices on the levels of cariogenic bacteria in
      human saliva.
AB  - This investigation evaluated the efficacy of two bicarbonate-containing
      dentifrices (one with fluoride and one without) against one placebo dentifrice
      (containing neither fluoride nor bicarbonate) in vivo in a panel of human
      volunteers to determine whether or not sodium bicarbonate would affect salivary
      mutans streptococci and lactobacilli. Ten caries-inactive adults were divided
      randomly into three groups, each of which was exposed to all three dentifrices,
      in a crossover manner, during three 4-week test periods. Saliva samples were
      taken at 1-week intervals. Samples were stored on ice, and microbiological
      analyses were conducted. The statistical analyses showed that, over a 4-week
      period, there was a statistically significant (p < 0.05) reduction in numbers of
      mutans streptococci with the two bicarbonate dentifrices as compared with the
      placebo dentifrice. Although not statistically significant, a similar trend was
      observed with lactobacilli. Longer-term, large-scale studies need to be conducted
      to investigate the possible mechanisms of action of sodium bicarbonate on these
      organisms and to relate the results to possible cariostatic effects in humans.

PMID- 7728830
TI  - Salivary mutans streptococci and incidence of caries in preschool children.
AB  - The aim of this study was to assess the relationship between salivary mutans
      streptococcus (SMS) levels and the prevalence and incidence of dental caries in
      148 children (mean baseline age 3.8 years) of low socioeconomic status. Caries
      data (dmfs) and semiquantitative SMS counts were obtained at baseline and
      annually for 2 years. The children were classified during each of the 3 years as
      low (0 colony-forming units; CFU), moderate (1-50 CFU), or high (> 50 CFU) caries
      risk based on total SMS counts. The results indicated that the prevalence of
      dental caries increased with SMS levels at baseline and generally in both
      assessment years. At baseline the mean dmfs of the children classified as low,
      moderate, or high caries risk was 0.15, 1.44, and 3.36, respectively, while the
      mean dmfs of the same children at year 2 was 1.18, 3.10, and 7.87, respectively.
      The mean dmfs of the high-caries-risk group increased by 79% between baseline and
      year 1 and by 30% between year 1 and year 2. At year 2, 50% of the children in
      the low- and 47% in the moderate-caries-risk groups were caries free as compared
      with 11% in the high-caries-risk group. Thirty-three percent of the children
      examined remained in the same caries risk category from baseline to year 2; the
      incidence (delta dmfs) of dental caries in those children designated as low,
      moderate, and high caries risk during this period was 1.44, 3.36, and 10.07,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728831
TI  - Comparison of selected microflora of plaque and underlying carious dentine
      associated with primary root caries lesions.
AB  - The composition of the microflora recovered from superficial dental plaque
      sampled from 81 primary root caries lesions requiring restoration was compared
      with the microflora of the underlying, infected carious dentine. The numbers of
      bacteria in the plaque samples were significantly greater than in the dentine
      samples, and the frequency of recovery of mutans streptococci, streptococci,
      lactobacilli, gram-positive pleomorphic rods (primarily Actinomyces spp.), and
      yeasts was not significantly different between the paired samples. However, the
      proportion of lactobacilli and gram-positive pleomorphic rods was significantly
      greater in the dentine, while the proportions of streptococci and yeasts did not
      differ significantly; the proportions of mutants streptococci were similar in
      both samples. These data indicate that the microflora overlying primary root
      caries lesions is significantly different from that associated with the infected
      root dentine. The method of sampling and culturing the microflora of root caries
      lesions must, therefore, discriminate between the microflora of the superficial
      supragingival plaque and the microflora associated with destruction of the
      infected underlying dentine.

PMID- 7728832
TI  - Streptococci and actinomyces inhibit regrowth of Streptococcus mutans on
      gnotobiotic rat molar teeth after chlorhexidine varnish treatment.
AB  - Clinical studies suggest that the long-term suppression of mutans streptococci on
      tooth surfaces after intensive chlorhexidine therapy is mainly due to bacterial
      interference. Other streptococci and also Actinomyces naeslundii are proposed to
      inhibit regrowth of mutans streptococci after suppression by the agent. We have
      tested this hypothesis in gnotobiotic rats associated with Streptococcus mutans
      alone, or associated with S. mutans and strains of Streptococcus oralis,
      Streptococcus sanguis, Streptococcus gordonii, Streptococcus mitis biovar I, and
      A. naeslundii. Left lower jaws in these rats were treated with concentrated
      chlorhexidine varnish, and the return of S. mutans on the treated jaws monitored.
      In mono-associated rats, S. mutans regained the level of the untreated right
      lower jaw in approximately 1 week. In contrast, S. mutans remained suppressed for
      several weeks in rats multi-associated with other streptococci and actinomyces
      strains. The suppression was more pronounced in the rats fed on basal diet with
      little free sugars than in rats fed on a sucrose-containing diet. Counts of other
      streptococci recovered quickly from the intensive chlorhexidine treatment, but A.
      naeslundii remained suppressed for at least 1 week. The findings demonstrate the
      crucial importance of the oral microflora in controlling regrowth of mutans
      streptococci after chemotherapy.

PMID- 7728833
TI  - In vivo diagnosis of fissure caries using a new electrical resistance monitor.
AB  - The aim of this investigation was to study the accuracy of a newly developed
      electrical resistance monitor in diagnosing occlusal fissure caries in vivo in
      teeth without cavitation. The electrical resistance was measured in vivo on human
      third molars without existing restorations and without any macroscopic carious
      cavitation. Data from 41 sites on 26 occlusal surfaces were obtained. After
      measurement, the teeth were extracted, histologically prepared, and serially
      sectioned perpendicular to the occlusal surface and examined for the presence of
      caries. Nineteen sites had no caries, 7 had enamel caries, and 15 sites showed
      dentinal caries, 4 of which deep dentinal caries. For the diagnosis of occlusal
      caries with the electrical resistance monitor, the specificity was 0.77, the
      sensitivity 0.93, and the accuracy 0.83. Likelihood ratios for four diagnostic
      levels (no caries, enamel caries, dentinal caries, and deep dentinal caries) were
      0.09, 0, 3.47, and 4.16, respectively. Diagnosis of occlusal caries using
      conventional bite-wing radiographs showed a specificity of 0.77, a sensitivity of
      0.62, and an accuracy of 0.71. The electrical resistance monitor was well suited
      to detect in vivo occlusal caries under clinically intact fissures. The rather
      high value (0.23) of false-positive ratings, however, might lead to a substantial
      number of sound teeth being restored unnecessarily. Substantial improvement of
      occlusal, caries diagnosis may be achieved by combining this method with others.

PMID- 7728834
TI  - Electrical conductance and electrode area on sound smooth enamel in extracted
      teeth.
AB  - Electrical conductance measurements are being used experimentally to diagnose
      caries. Current equipment, e.g. the electronic caries monitor (ECM), uses a probe
      to scan occlusal fissures. For full-mouth examination this method is rather time
      consuming. A method with which only one measurement is needed for an entire
      (occlusal) surface would be preferable. However, the enlargement of the area
      being measured will influence the conductance. It was the purpose of this study
      to investigate the relationship between the electrical conductance of human teeth
      and the enamel electrode area, and to compare the range of results of surface
      measurements with those of the scanning method. Twenty-five sound extracted teeth
      were selected for the study. The reference electrode of the ECM was connected to
      the roots. The buccal surface was blotted dry, and a coloured dentifrice was
      syringed in increments onto the surface. After each increment the surface was
      photographed together with a metric reference, a conductance measurement was
      performed by holding the ECM probe tip in the dentifrice, and the ECM reading was
      recorded. For each tooth between 5 and 10 increments were applied and measured.
      The photographs were digitised and the electrode areas were calculated. A least
      squares curve fitting procedure yielded a linear relationship between conductance
      and electrode area (0.88 < or = R2 < or = 1.0, mean R2 = 0.97). For most teeth
      the threshold for dentinal caries as used for scanning ECM measurements (ECM
      reading = 6.00) was reached only when the electrode area exceeded 12 mm2. For 6
      teeth this conductance was already reached between 5 and 12 mm2.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7728835
TI  - Electrical conductance of fissure enamel in recently erupted molar teeth as
      related to caries status.
AB  - Pit-and-fissure caries lesions contribute greatly to the caries incidence in
      permanent molar teeth in children. To date, the diagnosis of occlusal caries is
      still performed mainly by visual inspection, periodically aided by bite-wing
      radiography. However, in detecting small occlusal carious lesions, these methods
      perform inadequately, especially in low caries prevalence populations or
      individuals. The use of electrical conductance measurements (ECMs) has been
      evaluated to improve the diagnosis of small occlusal carious lesions. The aim of
      this study was to monitor the electrical conductance of fissure enamel in
      recently erupted molar teeth and to relate these measurements to the caries
      status. 50 children aged 5-15 years, having first or second permanent molars that
      were not exposed to the oral environment for more than 6 months, participated in
      the study. The diagnostic systems evaluated were visual inspection and ECMs.
      Following baseline data recording, diagnostic measurements were repeated three
      times within 18 months. Data were collected at predefined sites in the fissures.
      18 months after baseline recording, 179 sites at 60 molar teeth in 27 children
      were judged to require a sealant based on visual inspection. After removal of
      carious tissue, two examiners jointly decided on the status of decay as per the
      criteria: 0 = no caries or caries limited to enamel, and 1 = caries involving
      dentine. The sensitivity of ECM continued to increase with time after a slight
      initial dip, whereas the specificity continuously increased after baseline
      measurements as a result of the decreasing amount of false-positive
      diagnoses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728836
TI  - [Erythropoietin in the era of molecular biology].
AB  - Cloning of genes for erythropoietin in the mid-eighties started a new period of
      research and use of erythropoietin. RIA and ELISA methods of its detection were
      developed. It became possible to seek possibilities of its therapeutic use. The
      cell type which is the source of erythropoietin in the organism was assessed. The
      regulation of the expression of the erythropoietin gene in relation to oxygen
      tension was investigated. The biochemical mechanism is sought which transmits the
      oxygen tension to transcription signals and the stability of erythropoietin mRNA.
      The gene for the erythropoietin receptor was found and it is investigated in
      relation to the pathogenesis of primary polycythemias.

PMID- 7728837
TI  - [The effect of erythropoietin on fibrinolysis in hemodialyzed patients].
AB  - BACKGROUND: According to some data treatment with human recombinant
      erythropoietin (EPO) in dialyzed patients leads to a more frequent occurrence of
      thromboses. One of the possible causes could be reduced fibrinolysis. The
      objective of the present study was to assess the effect of EPO in dialyzed
      patients on two key enzymes of fibrinolysis, i.e. the tissue activator of
      plasminogen (t-PA) and the inhibitor of the plasminogen activator (PAI-1).
      METHODS AND RESULTS: In eight patients dialyzed for prolonged periods examined
      under otherwise equal conditions before EPO treatment (haematocrit 22.9%--median
      value) and after 9.5 weeks of EPO treatment (Recormon, s.c.) when a haematocrit
      of 30% was achieved, activities (chromogenic substrates) and antigens (ELISA of t
      PA and PAI) were assessed. All examinations were made before and after venous
      occlusion. Between examinations made before treatment and during EPO treatment no
      significant difference was found in the t-Pa activities assessed before venous
      occlusion (before EPO 0.9 IU/ml--during EPO 0.6, not significant Wilcoxon's
      paired test) nor after venous occlusion (3.2-3.8, n.s.). PAI activities before
      venous occlusion (10.9 U/ml-18.3, n.s.) and after venous occlusion (9.7-11.5,
      n.s.) did not differ significantly either, when comparing values before and in
      the course of EPO treatment. Similarly as in the case of activities in antigens t
      PA and PAI no difference was found before and during EPO. CONCLUSIONS: No effect
      of EPO on the investigated indicators of fibrinolysis was found. The results of
      the presented investigation are at variance with the idea that EPO reduces
      fibrinolysis in dialyzed patients and thus contributes to the development of
      thrombotic complications.

PMID- 7728838
TI  - [Lipoperoxides and their clinical importance].
AB  - BACKGROUND: Research and investigations in the sphere of lipid peroxides has been
      pursued so far for a relatively short time. Therefore every new finding is a
      great asset for this branch of medicine. An elevated lipid peroxide level
      signalizes pathological changes in the organism. Malondialdehyde is an indicator
      of lipid peroxidation. The authors focused their experimental work on assessment
      of malondialdehyde in human serum. They tested the effect of increased radical
      peroxidation caused by diabetes and investigated whether it raises the lipid
      peroxide level in a group of patients suffering from ischaemic heart disease.
      METHODS AND RESULTS: Two groups were formed--one comprising 10 patients with
      ischaemic heart disease and another one of 8 patients with ischaemic heart
      disease and type II diabetes. The malondialdehyde concentrations were moreover
      compared with a control group of healthy subjects. The mean age of the first
      group was 72 years, of the second group 69 years. The mean age of the control
      group was 64 years. Lipid peroxidation was assessed from the concentration of
      malondialdehyde using an analytical method--spectrophotometry with fluorescence
      detection. CONCLUSIONS: Statistical evaluation of lipid peroxide levels in the
      two groups of patients with ischaemic heart disease led to the conclusion that
      the differences were not significant. Type II diabetes did not cause a greater
      increase of lipid peroxides in patients with IHD.

PMID- 7728839
TI  - [Use of etofyllinclofibrate (Duolip Forte) in combined hyperlipidemia].
AB  - BACKGROUND: Duolip forte (ethophyllinclofibrate) is a lipid lowering drug, the
      effect of which was not yet adequately verified in our conditions, namely from
      the point of its effect on various types of hyperlipoproteinaemias. METHOD AND
      RESULTS: The therapy was applied on 45 patients with combined hyperlipidaemia, 25
      men and 20 women, mean age 53.8 years (age range 41-65). About one half of
      patients were treated for hypertension, almost one quart of them manifested
      ischemic heart disease, 13% had a history of myocardial infarction and the same
      percentage suffered from associated diabetes type 2. Duolip forte was
      administered perorally in a dose of 500 mg once daily for 12-16 weeks to the
      patients who had complied with the prescribed diet (weight loss, improvement of
      lipid levels) during three-month preliminary period, but did not reach desirable
      parameters. After the therapy, the whole group studied manifested a significant
      decrease of total cholesterol (-10.8%), LDL-cholesterol (-13%), triglycerides (
      40.8%) and free fatty acids (-20.6%), while the increase of HDL-cholesterol and
      its fractions was not significant. In hyperlipoproteinaemias of IIa type (n =
      15), only a significant decrease of LDL-cholesterol appeared, in
      hyperlipoproteinaemias of IIb type (n = 15), a significant decrease was evidenced
      only in triglycerides (-33.9%). In hyperlipoproteineaemias of IV type (n = 15), a
      significant decrease was observed in triglycerides (-50.3%), while HDL-2
      cholesterol values increased (+32.3%). A slight decrease of uric acid level and
      of body mass index observed in all groups was statistically not significant, as
      well as a slight increase of glycaemia and changes of serum transaminases. No
      unwanted side effects of Duolip were found. CONCLUSIONS: Ethophyllinclofibrate
      has proved as effective namely at hypertriglyceridemic primary hyperlipidaemias.
      Besides decreasing triglycerides, it increases significantly HDL-2 cholesterol. A
      convenient dosage, small lithogenic effect and minimum of side effects make it a
      drug of choice for some groups of elderly high-risk patients.

PMID- 7728840
TI  - [Hemoperfusion with Amberlite XAD-4 in acute theophylline poisoning].
AB  - Haemoperfusion through Amberlite XAD-4 was used in a female patient who took with
      suicidal intention 29 tablets of Syntophylline. During 5 hours of haemoperfusion
      the theophylline plasma concentration declined significantly to the lower limit
      of the therapeutic range. Early application of haemoperfusion, using Amberlite
      XAD-4, led to rapid regression of symptoms of acute intoxication and recovery of
      the patient.

PMID- 7728841
TI  - [The human genome--chromosome 5].
AB  - From the historical aspect the fifth human chromosome is associated with the cri
      du-chat syndrome conditioned by deletion of the short arms. The fifth human
      chromosome is the carrier of genes the pathogenic alleles of which cause one of
      the most frequent recessive hereditary diseases of child age--spinal muscular
      atrophy (SMA), the development of tumours of the large bowel and a group of
      haematological malignant conditions which are part of the so-called 5q-syndrome.
      It is the carrier of some important gene families-complement, interleukins and
      growth factors and their receptors; loss of some of them participates in the
      mentioned 5q-syndrome.

PMID- 7728842
TI  - [How alibis cost dearly in the USA--the case of Baby K].

PMID- 7728843
TI  - [History of clinical cytodiagnosis. II].

PMID- 7728844
TI  - Activated clotting times in acute coronary syndromes and percutaneous
      transluminal coronary angioplasty.
AB  - A discrete fall in the ACT (activated coagulation time) has been observed in
      patients with known activation of the coagulation cascade. Injury to the coronary
      artery resulting in thrombin activation, whether spontaneous as in the case of
      acute myocardial infarction or planned as with percutaneous transluminal coronary
      angioplasty (PTCA), may therefore be reflected in a change in ACT values. We
      reviewed the records of patients undergoing PTCA at St. Luke's Episcopal
      Hospital/Texas Heart Institute from January 1990 through December 1992 for
      information regarding ACT values and clinical events. A total of 469 patients,
      whose record contained adequate information for study inclusion, were divided
      into four separate groups: acute myocardial infarction (group I, n = 62),
      unstable angina with heparin therapy that was withdrawn at least 4 hr prior to
      PTCA (group II, n = 102), unstable angina with heparin therapy continued until
      the time of PTCA (group III, n = 154), and stable angina undergoing elective PTCA
      (group IV, n = 151). Heparin was discontinued 12-15 hr after the procedure in all
      but group I where anticoagulation was often maintained up to 72 hr. ACT values
      were measured prior to the PTCA procedure (baseline), after the initial heparin
      bolus of 10,000 U (postheparin) and approximately 12-18 hr after the procedure
      (heparin withdrawal).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728845
TI  - The efficacy of delaying intervention after diagnostic coronary arteriography.

PMID- 7728846
TI  - Development of a new technique for reducing pressure pulse generation during 308
      nm excimer laser coronary angioplasty.
AB  - Despite expectations that excimer laser ablation would result in a low incidence
      of coronary dissection, studies have documented a 15-20% incidence of dissection
      (including a 4-6% incidence of clinically significant dissection) during excimer
      interventions. This investigation sought to determine if pressure pulses produced
      by the exposure of fluid phase media (blood and contrast) to 308-nm excimer
      radiation might contribute to untoward outcomes. Pressure pulses generated in
      these media were quantitated to be > 100 atm. In vitro ablation of porcine aorta
      in the presence of blood or contrast resulted in tissue dissection, while
      ablation in pure crystalloid did not. Next, a "flush and bathe" technique
      designed to replace all blood and contrast with crystalloid was applied to a
      pilot population of 57 consecutive patients. There were no rhythm disturbances or
      laser-related clinically significant dissections in this group, and the clinical
      success rate was 95%. In summary, this report quantitates a potential etiology
      for excimer dissection and suggests that replacement of blood and contrast with
      crystalloid might improve procedural and clinical success rates.

PMID- 7728847
TI  - Balloon dilation of critical valvar pulmonary stenosis in the first month of
      life.
AB  - Between 1985 and 1992, 36 consecutive neonates, aged 1-29 days, weight 2.4-5.0
      kg, with critical valvar pulmonary stenosis underwent attempted balloon dilation
      (BD). At catheterization, 30 were on prostaglandin (PGE1) therapy and 20 were
      intubated. The valve was successfully crossed and dilated in 34/36 (94%),
      including three with an echocardiographic diagnosis of valvar pulmonary atresia
      and a right ventricle of adequate size. The valve was first dilated with a 2- to
      5-mm balloon and then with serially larger ones (up to 12 mm) to a final
      balloon/annulus value of 126%. The RV/systemic pressure value fell from 150 +/-
      32 to 83 +/- 30%, O2 saturation rose from 91 +/- 6% to 96 +/- 4%, and PGE1 was
      discontinued at the end of the procedure. There were 11 complications (31%)
      including one early death from sepsis and necrotizing enterocolitis, endocarditis
      in another, two myocardial perforations, one femoral-iliac vein tear, and one
      transient pulse loss. A repeat BD was carried out in five patients, two of whom
      subsequently had surgery. At follow-up (33 +/- 23 months), the 31 patients
      managed by BD alone were well and had echocardiographic gradients of < 30 mm Hg
      in 90% and pulmonary regurgitation, considered mild in most, in 52%. In neonates
      with critical valvar pulmonary stenosis, we believe BD mortality is less than
      with surgery and is the treatment of choice.

PMID- 7728848
TI  - Echocardiographic predictors of candidacy for successful transcatheter atrial
      septal defect closure.
AB  - We reviewed pre-closure echocardiograms on all patients undergoing transcatheter
      atrial septal defect (ASD) closure with the Bard double-umbrella occluder device
      aided by simultaneous transesophageal echocardiography to determine
      precatheterization predictors of outcome. Transesophageal echocardiograms were
      performed on 28 of 132 patients (22%) undergoing device closure (age = 3-72
      years, mean = 14 years; weight = 15-68 kg, mean = 35 kg). Three devices were
      removed because of unstable position. Of the remaining 25 patients, 21 had
      effective closure (residual flow diameter < or = 3 mm) and 18 had favorable arm
      position (device arm on proper side of the septum and not in contact with an
      atrioventricular valve leaflet). Only ASD size predicted effective closure. All
      patients with a maximum defect size of < 13 mm had effective closure. Among the
      17 patients with defects > or = 13 mm, 10 had effective closure, 4 had
      significant residual flow, and 3 had devices removed for unstable position.
      Atrial dimensions and rim size did not predict effective closure. There were no
      pre-closure predictors of favorable arm position which was associated only with
      the size of the device implanted.

PMID- 7728849
TI  - Partial and transient relief of conduit obstruction by low-pressure balloon
      dilation in patients with congenital heart disease.
AB  - Seven patients underwent attempted low pressure balloon dilation of stenotic
      conduits or homografts from right ventricle to pulmonary artery (n = 5), in the
      aortic valve position (n = 1), or from right atrium to left pulmonary artery (n =
      1). In the right ventricle to pulmonary artery group, mean gradient reduction was
      only 17%. At follow-up, two patients underwent surgical conduit replacement, one
      had a stent implanted at cardiac catheterization, the other two are awaiting
      surgical intervention. The patient with a homograft in the aortic valve position
      had a good initial result but restenosed within 1 year and underwent a pulmonary
      autograft operation. The patient with the Fontan homograft stenosis had transient
      obstruction relief but subsequently required stent implantation. Low-pressure
      balloon dilation of conduits or homografts is only partially and transiently
      successful. Whether stent implantation will offer better long-term results
      remains to be determined.

PMID- 7728850
TI  - Ballooning between a rock and a hard place.

PMID- 7728851
TI  - Transcatheter radiofrequency perforation and stent implantation for palliation of
      pulmonary atresia in a 3060-g infant.
AB  - In a 3060-g infant with fibromuscular pulmonary atresia an open right ventricular
      outflow tract was created by means of interventional cardiological methods.
      Following two inadvertent perforations without sequelae or clinical symptoms,
      radiofrequency perforation and subsequent balloon dilatation were successfully
      performed. The implantation of a Palmaz iliac stent led to a predictable
      communication between the right ventricle and pulmonary artery.

PMID- 7728852
TI  - From imagination to reality: how much can interventional cardiologists do for
      congenital cardiac anomalies?

PMID- 7728853
TI  - Ductus arteriosus rupture as a balloon catheter atrioseptostomy complication.
AB  - A newborn with transposition of the great arteries presented with rupture of the
      ductus arteriosus after balloon catheter atrioseptostomy. The necropsy study
      demonstrated persistent ductus patency, and a 0.5-cm-long horizontal fissure
      could be observed. On microscopy, there was laceration of the intimal layer, with
      wall dissection and focal hemorrhage extending to the adventitia. Ductus rupture
      was attributed to the wall weakness, as a consequence of prostaglandin E1
      administration.

PMID- 7728854
TI  - Transvenous coronary arteriography via ventricular septal defect for infants and
      children with tetralogy of Fallot.
AB  - Selective coronary arteriography was performed by the antegrade transvenous
      technique in 13 cases of young children with tetralogy of Fallot utilizing two
      specially designed catheters. Right coronary arteriography was successfully
      performed in all, and left coronary arteriography was successful in the latest
      four cases. The importance of the catheter design is discussed based on the
      anatomical characteristics of the anomaly.

PMID- 7728855
TI  - Septic endarteritis following percutaneous transluminal coronary angioplasty.
AB  - We report a case of bacterial arteritis of the external iliac artery complicated
      by mycotic aneurysm following coronary angioplasty. To our knowledge, this is the
      first reported instance of arterial wall infection caused by coronary angioplasty
      at a distance from the insertion site equal to the length of the sheath.

PMID- 7728856
TI  - The acts of coronary angioplasty.

PMID- 7728857
TI  - Damage to the collateral circulation by PTCA of an occluded coronary artery.
AB  - In this report, a patient is described with an occluded left circumflex artery,
      in whom the corresponding myocardium was protected at rest by sufficient
      collateral circulation. Because of angina pectoris class III, a PTCA of that
      occluded vessel was performed, complicated by a large dissection. Recruitable
      collateral flow, assessed from pressure calculations by a new technique, suddenly
      decreased at the very moment of dissection. This was accompanied by resting pain
      and ischemia on the ECG. This case report confirms the hypothesis that the
      collateral circulation can be damaged by PTCA and emphasizes that every PTCA
      implies a definite risk, even in case of an occluded coronary artery filled by
      collaterals.

PMID- 7728858
TI  - Collateral injury by total occlusion angioplasty: biting the hand that feeds us.

PMID- 7728859
TI  - Dynamic systolic coronary flow reversal and hyperemia in left anterior descending
      coronary blood flow velocity during Valsalva maneuver in a patient with
      hypertrophic cardiomyopathy.

PMID- 7728860
TI  - In vivo comparison of different quantitative edge detection systems used for
      measuring coronary arterial diameters.
AB  - Three different systems for quantitative coronary analysis [Cardiovascular
      Measurement System (CMS); Polytron 1000; Angiographic Workstation (AWOS)] were
      compared in 109 patients before and after coronary angioplasty and at follow-up
      coronary angiography. Correlation coefficients were low and 95% limits of
      agreement were wide. In general, CMS exhibited a tendency to yield lower values
      for very small diameters and higher values for larger vessels. The acute gain in
      minimal luminal diameter was considerably smaller when assessed by AWOS as
      compared to Polytron (0.52 vs. 0.71 mm, P < .0001) and to CMS (0.52 vs. 0.75 mm,
      P < .0001). Long-term gain was much larger when assessed by Polytron as compared
      to AWOS (18.8 vs. 11.5%, P < .001) and it was almost double for CMS as compared
      to AWOS (20.7 vs. 11.5%, P < .0001). In conclusion, in the individual patient
      very different results can be obtained when different QCA systems are used, and
      systematic differences between the systems are encountered.

PMID- 7728861
TI  - Femoral artery catheterization complications: a study of 503 consecutive
      patients.
AB  - This report describes a prospective randomized trial of 503 patients who
      underwent a cardiac catheterization or interventional procedure at a single
      institution. In an effort to study femoral complications postprocedure, we
      evaluated three methods of femoral artery hemostasis as well as 38 variables that
      were felt to potentially relate to local complications. Only a marginally
      significant relationship between the hemostasis method and complication rate was
      found. The factors that contributed to femoral artery complications were:
      restarting heparin postsheath removal, number of procedures done during one
      hospitalization, noncompliance of the patient with bedrest after the procedure,
      number of arterial punctures to initiate the procedure, and preprocedure
      treatment with corticosteroids.

PMID- 7728862
TI  - Clinical application of a new Palmaz-Schatz coronary stent delivery system with a
      short (8 mm) nonarticulated stent.
AB  - The standard Palmaz-Schatz coronary stent delivery system (SDS), with a 15 mm
      articulated stent and a 5F protective sheath, is relatively rigid and high in
      profile. Its use is contraindicated in vessels where there is severe tortuosity
      proximal to or in the lesion itself. Recently a new SDS, with a short (8 mm)
      nonarticulated stent, has become available. We present three patients with
      complex coronary anatomy solved with this new SDS. The first patient had a distal
      stenosis in an extremely tortuous and diffusely diseased right coronary artery
      (RCA). The second patient had a severe proximal RCA stenosis occurring at a bend
      of more than 90 degrees. The third patient had a very long stenosis of the left
      anterior descending coronary artery involving the ostium, requiring multiple
      tandem stenting. The availability of this short stent will greatly expand the
      clinical application of intracoronary stenting to patients with complex coronary
      anatomy.

PMID- 7728863
TI  - Reduction of femoral arterial bleeding post catheterization using percutaneous
      application of fibrin sealant.
AB  - The number of cardiac catheterizations performed yearly is growing with
      correspondingly increasing amounts of morbidity, complications, and hospital
      costs. This study suggests that fibrin sealant instillation via an arterial
      sheath at the completion of femoral catheterization may improve hemostasis.
      Results using fibrin sealant in 12 unheparinized dogs documented significant
      reductions (McNemar's exact test) versus control for groin ecchymoses (1 versus
      8, P = .008) and radiolabeled hematoma formation (0 versus 7, P = .016). Also
      swelling was less in the fibrin sealant treated groins when compared to control
      groins (1 versus 6, P = .125), but failed to reach statistical significance.
      Results in eight heparinized dogs (activated clotting time 374 +/- 22, mean +/-
      SEM) revealed a statistically significant reduction in signs of gross bleeding in
      the fibrin sealant-treated groins (1 versus 8, P = .016). This method may
      contribute to reduced morbidity, complications, and length of hospitalization. It
      may also allow for earlier patient mobilization after cardiac catheterization.

PMID- 7728864
TI  - Concentration of cofilin, a small actin-binding protein, at the cleavage furrow
      during cytokinesis.
AB  - Cofilin is a small actin-binding protein which regulates actin polymerization in
      a pH-dependent manner. Immunofluorescence microscopy with a monoclonal antibody
      for cofilin revealed that this protein is temporarily concentrated at the
      contractile ring during cytokinesis. Cofilin appeared to accumulate rapidly at
      the contractile ring during late stages of furrowing, and was finally enriched at
      the midbody. The concentration of cofilin at the contractile ring was observed in
      several kinds of cultured cells. Furthermore, cofilin introduced into living
      cells by a microinjection method was also concentrated at the contractile ring.
      These results suggest that cofilin is involved in actin reorganization during
      cytokinesis.

PMID- 7728865
TI  - Extrusion of rotating microtubules on the dynein-track from a microtubule-dynein
      gamma-complex.
AB  - Applying a new in vitro motility assay system for microtubules and 22S dynein, we
      recently reported on an ATP-induced extrusion of microtubules from microtubule
      dynein alpha- and beta-complexes [Mimori and Miki-Noumura, 1994: Cell Motil.
      Cytoskeleton 27:180-191]. In the present study, we prepared a gamma-complex by
      copolymerizing porcine brain tubulin and Tetrahymena ciliary 22S dynein, and
      examined the ATP-induced microtubule movement from the gamma-complex. The
      extrusion process appeared quite similar to that of the beta-complex. The sliding
      velocity was 18.39 +/- 2.20 microns/sec, which was a value comparable to that of
      trypsin-digested flagellar axonemes [Yano and Miki-Noumura, 1980: J. Cell Sci.
      44:169-186]. Higher velocity may be due to a densely arranged dynein-track with
      the same polarity, which was detached from the gamma-complex and absorbed in rows
      on a glass surface of the slide. Sometimes a free-floating microtubule in the
      perfusion chamber was observed riding and sliding on the dynein-track remaining
      on the slide after extrusion. Unexpectedly, we found that when the front part of
      the microtubule was fixed to a glass surface, a continuous sliding microtubule at
      the rear part on the dynein-track often transformed into a left-handed helix, and
      subsequently a twisted helix with several turns. The helix formation may be due
      to some rigidity in the microtubule and a right-handed torque component in the
      sliding force of 22S dynein. The addition of ATP may release some distortion
      accumulated in the complex structure during copolymerization of tubulin and 22S
      dynein, inducing reverse rotation of the microtubule.

PMID- 7728866
TI  - Phospholipid membrane-associated brush border myosin-I activity.
AB  - Brush border myosin-I (BBMI) is associated with the membrane of intestinal
      epithelial cells where it probably plays a structural role. BBMI also has been
      identified on Golgi-derived vesicles in intestinal epithelial cells where it may
      translocate vesicles into the brush border. However, the mechanochemical activity
      of BBMI bound to a phospholipid membrane has not been described. This study
      reports that phospholipid membrane-associated BBMI displays ATPase activity when
      bound to phospholipids, but does not move actin filaments when associated with a
      phospholipid bilayer. BBMI does not bind significantly to brush border membrane
      lipids, which contain about 16% phosphatidylserine (PS), in either a pelleting or
      planar membrane assay. Similarly, planar membranes containing 20% PS do not bind
      a significant amount of BBMI. Increasing the concentration of PS to 40% does
      result in the binding of BBMI to both vesicles and planar membranes. This binding
      is enhanced with increased Ca2+ concentrations. BBMI retains its ATPase activity
      when bound to phospholipid vesicles containing 40% PS. However, BBMI attached to
      a phospholipid bilayer surface does not move actin filaments, even though the
      amount of BBMI bound to the lipid surface, as reflected by the number of actin
      filaments associated with bilayer-bound BBMI, is sufficient to observe motility
      in control experiments. When membrane fluidity is reduced by adding cholesterol
      to the membrane lipids containing 40% PS, BBMI still binds to the membrane, but
      again no actin filament motility is observed. The lack of binding by BBMI to
      brush border membrane lipids and the absence of membrane-associated BBMI
      mechanical activity suggest that factors in addition to membrane lipids are
      necessary for membrane-associated myosin-I motility.

PMID- 7728867
TI  - Listeria monocytogenes intracellular migration: inhibition by profilin, vitamin D
      binding protein and DNase I.
AB  - Infection of host cells by Listeria monocytogenes results in the recruitment of
      cytoplasmic actin into a tail-like appendage that projects from one end of the
      bacterium. Each filamentous actin tail progressively lengthens, providing the
      force which drives the bacterium in a forward direction through the cytoplasm and
      later results in Listeria cell-to-cell spread. Host cell actin monomers are
      incorporated into the filamentous actin tail at a discrete site, the bacterial
      actin tail interface. We have studied the consequences of microinjecting three
      different actin monomer-binding proteins on the actin tail assembly and Listeria
      intracellular movement. Introduction of high concentrations of profilin
      (estimated injected intracellular concentration 11-22 microM) into infected PtK2
      cells causes a marked slowing of actin tail elongation and bacterial migration.
      Lower intracellular concentrations of two other injected higher affinity monomer
      sequestering proteins, Vitamin D-binding protein (DBP; 1-2 microM) and DNase I (6
      7 microM) completely block bacterial-induced actin assembly and bacterial
      migration. The onset of inhibition by each protein is gradual (10-20 min)
      indicating that the mechanisms by which these proteins interfere with Listeria
      induced actin assembly are likely to be complex. To exclude the possibility that
      Listeria recruits preformed actin filaments to generate the tails and that these
      monomer-binding proteins act by depolymerizing such performed actin filaments,
      living infected cells have been injected with fluorescently labeled phalloidin (3
      microM). Although the stress fibers are labeled, no fluorescent phalloidin is
      found in the tails of the moving bacteria. These results demonstrate that
      Listeria-induced actin assembly in PtK2 cells is the result of assembly of actin
      monomers into new filaments and that Listeria's ability to recruit polymerization
      competent monomeric actin is very sensitive to the introduction of exogenous
      actin monomer-binding proteins.

PMID- 7728868
TI  - Cytoskeletal domains in the activated platelet.
AB  - Platelets circulate in the blood as discoid cells which, when activated, change
      shape by polymerizing actin into various structures, such as filopodia and stress
      fibers. In order to understand this process, it is necessary to determine how
      many other proteins are involved. As a first step in defining the full complement
      of actin-binding proteins in platelets, filamentous (F)-actin affinity
      chromatography was used. This approach identified > 30 different proteins from
      ADP-activated human blood platelets which represented 4% of soluble protein.
      Although a number of these proteins are previously identified platelet actin
      binding proteins, many others appeared to be novel. Fourteen different polyclonal
      antibodies were raised against these apparently novel proteins and used to sort
      them into nine categories based on their molecular weights and on their location
      in the sarcomere of striated muscle, in fibroblasts and in spreading platelets.
      Ninety-three percent of these proteins (13 of 14 proteins tested) were found to
      be associated with actin-rich structures in vivo. Four distinct actin filament
      structures were found to form during the initial 15 min of activation on glass:
      filopodia, lamellipodia, a contractile ring encircling degranulating granules,
      and thick bundles of filaments resembling stress fibers. Actin-binding proteins
      not localized in the discoid cell became highly concentrated in one or another of
      these actin-based structures during spreading, such that each structure contains
      a different complement of proteins. These results present crucial information
      about the complexity of the platelet cytoskeleton, demonstrating that four
      different actin-based structures form during the first 15 min of surface
      activation, and that there remain many as yet uncharacterized proteins awaiting
      further investigation that are differentially involved in this process.

PMID- 7728869
TI  - Tubulin gene expression during growth and maturation of leaves with different
      developmental patterns.
AB  - Changes in the tubulin-protein and -poly(A) +RNA contents were monitored by means
      of Western and Northern blot analyses, respectively, during growth and maturation
      of leaves of a dicotyledonous (tobacco) and monocotyledonous (barley) plant. It
      was recently argued from immunofluorescence and preliminary biochemical data that
      the density of microtubular networks and concomitantly the tubulin content are
      distinctly reduced after cessation of cell growth in leaves [Jung et al., 1993].
      The results presented now confirm and extend this view. There appeared to be
      clear differences between the monocot and the dicot: (1) the loss of tubulin
      during leaf development was much slower in the dicot than in the monocot leaves
      (within months instead of days); (2) the degree of loss was more dramatic in the
      monocot leaf and only very low threshold levels of tubulin were retained in fully
      differentiated tissues; and (3) the loss of tubulin in the monocot leaf tissue
      appeared to be correlated with the decrease in the mRNA content, whereas the high
      level of tubulin-RNA in fully differentiated or even almost senescent dicot
      leaves indicated a gene expression control at the posttranscriptional level. The
      comparatively rapid and very distinct tubulin-protein and -RNA disappearance
      during development of the monocot leaf tissues confirm at the molecular level
      that differentiation proceeds much faster and is much more determinative in these
      leaves, as was postulated from histological and physiological data.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7728870
TI  - Identification and molecular characterization of a yeast myosin I.
AB  - The family of myosin motors is comprised of numerous classes distributed among a
      diverse set of organisms and cell types. We have identified an unconventional
      myosin gene (MYO3) in the yeast Saccharomyces cerevisiae and show that it is
      member of a subclass of unconventional myosin proteins originally found only in
      the amoeboid organisms Dictyostelium and Acanthamoeba. Identification of this
      protein in these genetically and morphologically divergent organisms suggests
      that it will be ubiquitous in eukaryotes and that it has a role in the basic
      functions of the eukaryotic cell. We have constructed a strain of yeast missing
      99% of the MYO3 coding sequence. This mutation has no observable phenotypic
      effect, placing MYO3 into a growing class of yeast genes which are dispensable
      under laboratory conditions, perhaps due to genetic redundancy. Alignment of MYO3
      with other unconventional myosins shows that it shares with a subset of them a
      previously unrecognized region of homology in the tail; this region falls within
      a domain identified as important for mediating nonspecific electrostatic
      interactions with membranes. The existence of this region suggests that it may be
      involved in mediating specific protein-protein interactions, possibly helping to
      localize this myosin to specific membranes or membrane regions. In addition, we
      show that "classic" myosin I proteins share a region of hyper-proline-richness 10
      amino acids before the SH3 domain. Proline-rich regions have recently been
      implicated as SH3 binding sites, which suggests that this region might be
      involved with regulating or in other ways interacting with SH3 domains.

PMID- 7728871
TI  - Ni2+ inhibition induces asymmetry in axonemal functioning and bend initiation of
      bull sperm.
AB  - Bull sperm extracted with 0.1% Triton X-100 can be reactivated to full motility
      with 0.33 mM Mg-ATP (sperm models). When motile sperm models are treated with
      0.66 mM NiSO4, spontaneous motility is lost. During the transition to motility
      arrest, the beat becomes progressively more asymmetric, finally arresting at one
      extreme of the beat cycle. After spontaneous motility has been lost, the
      flagellum retains the ability to respond to mechanical stimulation. If a
      microprobe is used to bend the flagellum in the direction opposite to its own
      prevailing curvature and released, the recoil is rapid and overshoots the
      equilibrium position. When the same flagellum is manipulated in the opposite
      direction (into a tighter bend of the existing curve), the recoil is slower and
      does not exceed the initial bend. If a microprobe is used to carefully bend the
      whole flagellum into a curve, the flagellum will resume continuous beating, but
      only if the imposed bend is in the direction opposite the natural curvature. The
      reinstated beating activity (mechanical reactivation) is sustained as long as the
      flagellum is held by the microprobe. The rate of change of the shear angle in
      these mechanically reactivated, Ni(2+)-inhibited sperm suggests an impaired rate
      of sliding on one side of the axoneme compared to similarly restrained control
      sperm. It appears that Ni2+ has a selective inhibitory effect on the dynein arms
      that bend the flagellum in one direction. Furthermore, the remaining functional
      arms activate only when the flagellum is bent in the direction opposing their own
      action.

PMID- 7728872
TI  - Tropical rheumatology. Epidemiology and community studies: Latin America.
AB  - Over the past two decades in Latin America, there has been a slow but definite
      upsurge in studies on the epidemiology of RD but, thus far, the data on the
      distribution and determinants of RD in the population are limited, and knowledge
      of time trends and geographical differences in disease risk are lacking. It is
      still not clear what proportion of disabilities are due to RD. The impact of RD
      on communities in developing countries is believed to be substantial, due to the
      cost of treatment and rehabilitation, and loss of earnings. There are important
      gaps in our knowledge, leaving unanswered such questions as the cost of treatment
      and rehabilitation, and loss of earnings. There are important gaps in our
      knowledge, leaving unanswered such questions as the cost to society of RD and the
      potential impact of RD prevention on the overall burden of disability. It is also
      important to point out, however, that from the relatively simple descriptive
      studies which dominated the RD literature a few years ago, we are now witnessing
      a shift towards increasing sophistication in study design and incorporation of
      multicentre collaboration. The rheumatologists and epidemiologists in LA who have
      managed to continue their work merit admiration. Even with unavoidable omissions,
      this summary demonstrates that the epidemiology of RD is alive and well in LA,
      where it has managed to continue to function under extremely difficult
      conditions. Yet, few methodologists appear to have directed their attention to
      the unique challenges of conducting studies in a resource-poor
      environment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728873
TI  - Tropical rheumatology. Epidemiology and community studies: Asia/Pacific region.
AB  - It has been recognized that the remarkable decline in infant mortality and the
      extension in human lifespan involving both developing and developed countries
      alike, has been influenced by social and economic developments and public health
      orientated measures (such as clean water and sewerage) rather more than by
      developments in medical research. However, the identification of important
      disease risk factors for a number of common conditions such as smoking, solar
      exposure, dietary fat and alcohol has led to further reductions in disease
      prevalence and mortality, at least in some countries. The varied success of
      strategies to reduce the mortality from circulatory, nutritional and diseases due
      to infection has had the predictable result of leaving communities more exposed
      to the chronic non-communicable diseases, especially those affecting the elderly.
      The COPCORD community-based studies, carried out largely in tropical Asia/Pacific
      countries, have indicated that the burden of musculoskeletal conditions as far as
      pain and disability, as well as from an economic point of view, are substantial
      and WHO has called for increased research and educational activities into the
      causes and consequences of chronic disease and in particular rheumatic diseases.
      To the problems of an increasing ageing population can be added the rapid growth
      of urban populations, new occupational stresses, lifestyle changes and a number
      of other factors (WHO, 1984). The common community-based rheumatic diseases are
      not RA or SLE that dominate admissions to hospital arthritis clinics. Pain and
      disability are most often caused by osteoarthritis, especially knee OA, and
      various soft tissue rheumatic problems producing neck, back, shoulder and elbow
      pain. Viral and reactive arthritis cannot be ignored and the complications from
      osteoporosis (although not normally considered a rheumatic condition), are a
      significant threat to ageing populations worldwide. It is clear that for many of
      these conditions, certain risk factors have been identified and that preventative
      strategies are becoming available although far more detailed research is still
      required (Wigley, 1993). Community education is an essential part of prevention
      and treatment and the ILAR-sponsored publication Aches and Pains--Living with
      Arthritis and Rheumatism (Hampton, 1992) is available in at least 10 different
      languages and fills an important need. Education helps to influence not only
      knowledge but also skills and attitudes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7728874
TI  - Rheumatic fever.
AB  - The incidence of RF and RHD in the tropics remains high, with a high proportion
      of children suffering from carditis with the first attack. Severe, incapacitating
      haemodynamic disturbances occur early. Many patients are seen with established
      RHD at their first visit, and the default rate is high. Poverty, overcrowding,
      poor transport facilities, understaffed and overburdened clinics, and poor follow
      up add to the problem. A genetic predisposition to develop RHD appears to be
      important in certain countries like India, Egypt and Turkey, but no work to show
      this has been done in black Africa. Secondary prophylaxis remains the most
      practical means of controlling the disease in the tropics. Compliance with long
      term prophylaxis depends on organized and concerted efforts of physicians, other
      health personnel, parents, teachers, and the community.

PMID- 7728875
TI  - Viral infections: musculoskeletal infection in the human immunodeficiency virus
      (HIV) infected patient.
AB  - HIV disease has reached epidemic proportions in Africa over the last decade and
      is severely stretching the health services of the many poor countries of the
      region. Increased sepsis during fracture surgery and the late infection of
      implants impels us to rethink many standard methods of treatment. Musculoskeletal
      infections, including tropical pyomyositis and long bone haematogenous
      osteomyelitis, are now common manifestations of advanced HIV disease in adults.
      Despite their severe infections, such patients may survive for more than 5 years
      and certainly cannot be written off as terminally ill. Treatment is often
      prolonged and, in the case of osteomyelitis, may necessitate amputation. These
      patients now occupy many of the available orthopaedic beds.

PMID- 7728876
TI  - Viral infections: arthritis in the human immunodeficiency virus (HIV) infected
      patient.
AB  - Reactive arthritis is common in HIV-positive patients and may be mistaken for
      septic arthritis. We feel that the association is probably, in part, due to the
      increased incidence of diarrhoeal diseases in HIV-infected patients rather than a
      specific effect of HIV on the synovium. Disabling, chronic, sero-negative
      polyarthritis is common in the later stages of HIV infection and further
      palliative therapeutic strategies are urgently needed.

PMID- 7728877
TI  - Viral infections: alpha-viral arthropathy.
AB  - Six different mosquito-borne viruses (Chikungunya, O'nyong-nyong, Mayaro, Ross
      River, Sindbis and Barmah Forest) have been associated with arthritis in humans.
      These viruses are prevalent in the tropics and subtropics and they produce
      similar symptoms, consisting of fever, joint pains and rash. The symptoms are
      usually of short duration, around 1 week; complete recovery is the rule apart
      from exceptional cases of Chik infection. Precise diagnosis requires a
      serological service which is not available in many parts of the tropics these
      days. Treatment is symptomatic and there is no vaccine currently available. With
      an increasing number of visitors to the tropics being exposed to potential
      infection and with rapid air transport it is possible that visitors may return
      home during the viraemic incubation stage, infect the local mosquito populations
      and then develop clinical disease.

PMID- 7728878
TI  - Bacterial infections: bone and joint tuberculosis.
AB  - In many countries of the world, there is now a dual epidemic of tuberculosis and
      HIV disease. HIV specifically eliminates the tissue macrophages and CD4
      lymphocytes, the very cells that provide immunity against tuberculosis.
      Tuberculosis is one of the more virulent opportunistic infections and it
      therefore appears fairly early in HIV disease. For the same reasons, bone and
      joint tuberculosis is becoming much more common. The disturbances of the
      lymphocyte count, ESR and antigen skin tests associated with HIV, now often make
      tuberculosis difficult to distinguish from other inflammatory lesions. The only
      change in the pattern of disease that we have so far registered is an increased
      incidence of disease affecting the lumbar spine. HIV-positive patients respond
      poorly to chemotherapy and are subject to drug sensitivity reactions. Major
      surgery is fraught with infectious complications and should be avoided. Once
      Pott's paraplegia has developed, the demise of the HIV-positive patient is rapid.

PMID- 7728879
TI  - Bacterial infections: osteoarticular brucellosis.
AB  - Osteoarticular brucellosis has been documented extensively from the Middle East
      and Spain in the last 5 years, but it has only been reported infrequently from
      the UK and USA. Brucella melitensis from goat and sheep is the most frequently
      isolated organism. Peripheral articular pain, particularly of the large joints,
      is the commonest osteoarticular manifestation, while effusions that seldom yield
      organisms on culture, also occur frequently. Sacroiliitis which most frequently
      is unilateral, often presents acutely and dramatically with severe pain that is
      poorly localized to the lower back and buttock, leading to difficulty in walking
      and even standing. Tapping the heel and springing the sacrum is probably the best
      way of localizing the pain to the sacroiliac joint in this acute stage. Lack of
      awareness of this pattern of presentation could lead to misdiagnosis. Spondylitis
      is the third major manifestation of osteoarticular brucellosis. It occurs in
      older patients and is insidious and chronic in onset and course. The lumbar spine
      is most frequently involved, although cervical involvement is frequently
      associated with more complications, particularly compressive neurological
      deficits. Osteomyelitis occurs unusually. Several large series have been reported
      among children. In them peripheral large joint involvement in association with
      systemic features predominate while sacroiliitis may occur unusually. Plain X
      rays often demonstrate vertebral damage, involving the upper anterior margin most
      frequently. CT scans define better vertebral damage that is characterized by bony
      sclerosis and the less frequently encountered extradural extension and para
      vertebral abscess formation. Technetium bone scan is the most sensitive technique
      for detecting acute sacroiliitis and other sites of early osteoarticular
      involvement. A four-fold rise in Brucella agglutination titre is the most
      frequently utilized diagnostic aid. A 6 week culture in a CO2-enriched medium is
      recommended for growing Brucella. Tetracycline or doxycycline 200 mg per day for
      6 weeks is the mainstay of most medical treatment schedules. Combination with
      streptomycin for 3 weeks or rifampicin for 6 weeks is recommended, to reduce
      significantly the failure and relapse rate. Spinal involvement is associated with
      an increased failure and relapse rate while they occurred least among those with
      no osteoarticular involvement. Surgical intervention to stabilize the spine and
      relieve neurological compression may become necessary. With the use of these
      various measures, the outlook for complete recovery is good.

PMID- 7728880
TI  - Bacterial infections: the arthritis of leprosy.
AB  - Arthritis is a common feature of leprosy and contributes to disability. Direct
      invasion of joints and bones by mycobacteria may lead to a destructive arthritis
      in lepromatous disease. The infective process may involve few or many joints.
      Reactional states may occur spontaneously but usually after the initiation of
      anti-mycobacterial treatment. In both the type 1 reaction of borderline case and
      the type 2 reaction of the lepromatous disease, intense inflammation may occur at
      sites of infection. The immunology of the reactions is different but they share
      clinical features including a polyarthritis which may resemble rheumatoid
      disease. The joint disease may be chronic or relapsing, affecting the wrists and
      small joints of the hands in particular. Radiological erosions may occur.
      Mycobacterium leprae is not found in the synovium in this pattern of arthritis.
      Further study of this phenomenon might yield useful information above the
      mechanism of joint inflammation in other rheumatic diseases.

PMID- 7728881
TI  - Bacterial infections: pyomyositis.
AB  - Staphylococcal pyomyositis is an important and common condition in many areas in
      the tropics. The cause is probably multifactorial and includes damage to the
      skeletal muscle in the presence of staphylococcal bacteraemia, with or without
      depressed immunity. In Africa, there are indications of an increased prevalence
      in association with HIV infection in young adults in whom multiple and recurrent
      abscesses are common. Long bone osteomyelitis is an important differential
      diagnosis in these patients. Timely surgical drainage and antibiotics leads to
      resolution. Delayed diagnosis is associated with disseminated disease and septic
      cardiorespiratory complications.

PMID- 7728882
TI  - Rheumatic syndromes associated with parasites.
AB  - A variety of musculoskeletal syndromes has been described in association with
      numerous parasitic infestations. Arthritis, enthesitis, myositis and vasculitis
      have been described in infected individuals resident in, or visitors to, endemic
      areas. The diagnosis of parasitic rheumatism is supported by poor response to
      anti-inflammatory drugs and improvement following antiparasitic treatment.

PMID- 7728883
TI  - Tropical rheumatology. Epidemiology and community studies: Africa.
AB  - There is still far too little information available on the rheumatic diseases in
      Africa. Epidemiological studies are required in order to determine the burden of
      illness from rheumatic diseases on the African continent as well as to identify
      local risk factors for certain diseases. Such studies will also serve to enable
      the development of preventative and rehabilitation strategies. Functional
      disability has to be assessed in relation to the prevailing sociocultural
      lifestyle on the continent. Measures of disability that reflect this await
      development whilst regional diagnostic criteria also need to be worked out. The
      validity of tests and the stability of test reagents in a tropical climate
      require analysis. Continuing assessment of rheumatological services is essential
      to ensure their effectiveness and efficiency in the community and in particular
      to determine health care priorities and the best forms of therapeutic
      intervention. This will enable judicious use of limited resources. Community
      surveys in Africa are fraught with constraints and are difficult to undertake
      owing to a shortage of manpower and financial resources. For this reason, most
      studies hitherto have been hospital based. Hospital studies though useful lack
      applicability to the population as a whole and consequently more emphasis on
      cross-sectional and longitudinal community studies are required. It is hoped that
      despite the restraints, these studies will be performed.

PMID- 7728884
TI  - Tropical rheumatology. Immunological aspects.
AB  - The presence of auto-antibodies in infectious diseases continues to puzzle and
      provoke. It is hoped that sequencing studies in particular will yield further
      clues as to the role and mechanism of production of autoantibodies in infectious
      diseases. This, in turn, may also provide further insights into the role of auto
      antibodies in auto-immune diseases. From a practical clinical viewpoint, the
      search for improved auto-antibody tests and new diagnostic markers with improved
      sensitivity and specificity must continue in the tropics. Until this is achieved,
      the results of auto-antibody tests in persons living in the tropics, persons from
      the tropics or patients with tropical infections, must be interpreted with
      caution.

PMID- 7728885
TI  - Tropical rheumatology. Treatment issues.

PMID- 7728886
TI  - Rheumatoid arthritis and connective tissue disorders: sub-Saharan Africa.
AB  - Rheumatoid arthritis (RA) once a rarity in Africa, is now reported in large
      numbers from many parts of Africa. Although epidemiological surveys have shown
      that the prevalence in urban populations is similar to Western communities, it is
      less common in rural areas. Further epidemiological studies are needed to confirm
      these findings in other parts of Africa and identify factors contributing to this
      difference to provide a better understanding for the emergence of RA in Africa.
      Earlier reports suggested that in African blacks RA was a mild disease, severe
      radiographic changes were uncommon, deformities were rare and extra-articular
      features were unusual and only symptomatic therapy was necessary to control
      symptoms in most patients. Recent experience shows that severe disease with
      deformities and radiographic changes are seen and a wide spectrum of extra
      articular features are noted although they may be less common than in Caucasians.
      African blacks with RA may have a younger age of onset and the genetic
      association with HLA DR4 has been confirmed. Systemic lupus erythematosus (SLE)
      is also recognized more often in African blacks who have a younger age of onset.
      SLE is also recognized less often in males. Features such as photosensitivity and
      serositis are less common while renal disease is more common. A reported short
      term mortality of about 30% emphasizes the need for urgent efforts to improve the
      prognosis in SLE. The infrequent occurrence of localized systemic sclerosis and
      the absence of anti-centromere antibodies in blacks was noted in a recent large
      series of patients with systemic sclerosis. The other connective tissue diseases
      and systemic vasculitides are reported much less frequently and will probably be
      detected more often in future. Anti-cardiolipin antibodies are detected
      frequently in association with infections, including HIV infection. The spectrum
      of diseases associated with ANCA includes a variety of connective tissue diseases
      and infections such as HIV infection and invasive amoebiasis must be added.

PMID- 7728887
TI  - Rheumatoid arthritis and connective tissue disorders: India and South-East Asia.
AB  - With a few exceptions, there remains a paucity of good epidemiological studies
      from India and South-East Asia. The overall impression is that the prevalence of
      rheumatoid arthritis (RA) is slightly less compared with the West and follows a
      milder course. There may be differences in the articular expression of the
      disease with the wrist and forefoot less commonly affected than in Caucasian
      studies. Extra-articular manifestations and erosive change are less frequent and
      severe. HLA DR4 does not correlate with seropositivity and severity of RA. The
      prevalence of SLE may be less in the Indian subcontinent than in the West.
      However, recent indications are that in South-East Asia and the Pacific region
      the prevalence morbidity and mortality are higher than in developed countries. An
      improvement in socio-economic conditions may be accompanied by an improvement in
      the survival of patients with SLE.

PMID- 7728888
TI  - Rheumatoid arthritis and connective tissue disorders: juvenile chronic arthritis.
AB  - That juvenile chronic arthritis (JCA) occurs in tropical countries there is no
      doubt. The spectrum of differential diagnoses is wider than in temperate regions.
      The disease tends to be more severe irrespective of the type of onset, and there
      is a high incidence of positive rheumatoid factor. Many cases present with
      advanced disease. There is a need for the establishment of clinics devoted
      specifically to the detection, documentation, and treatment of JCA.

PMID- 7728889
TI  - Osteoarthritis.
AB  - There are few studies on the prevalence, pattern or clinical course of
      osteoarthritis (OA) in the tropics. The studies that have been carried out,
      however, indicate that on the whole there is a lower prevalence of OA than found
      in Western countries. In addition, the pattern of joint involvement may be
      different with less common involvement of the hip relative to the knee and
      polyarticular OA is uncommon in many parts of the tropics. It also seems likely
      that a significant number of these patients in the tropics have OA secondary to
      various infections including pyogenic, tuberculous and parasitic infections.
      There is an urgent need to confirm these observations and to identify possible
      genetic, developmental or environmental factors influencing the expression of OA
      in the tropics. In addition degenerative arthropathies, such as Mseleni's
      disease, present in some parts of the tropics, merit further study. With
      increasing life-expectancy and improved health-care in many parts of the tropics,
      OA will become an increasingly prevalent and important condition with associated
      morbidity and socio-economic implications for these countries.

PMID- 7728890
TI  - Endemic fluorosis.
AB  - The presence of excessive quantities of fluorine in drinking water is accompanied
      by a characteristic sequence of changes in teeth, bone and periarticular tissues.
      These changes lead to a variable degree of locomotor disability, ranging from
      simple mechanical back pain to severe, crippling, combined locomotor and
      neurological impairment. In endemic areas, a substantial proportion of the
      population may be affected, posing a severe public health problem. In some areas,
      the hazards to human health are not fully appreciated and are under-reported. The
      maximum impact is felt in those communities engaged in physically strenuous
      activities, either agricultural or industrial. The need of these often isolated
      communities in economically hard-pressed countries, for the provision of low
      fluoride drinking water remains a hope rather than an expectation at the present
      time.

PMID- 7728891
TI  - Gout and hyperuricaemia.
AB  - We have recounted the remarkable story of gout and hyperuricaemia in the
      indigenous populations of the Pacific and noted the recent identification of the
      same problem in communities in rural Indonesia. Gout is increasingly recognized
      in African populations, especially in urban centres. There is no doubt that gout
      is 'alive and well' and presents a continuing challenge to future generations in
      developing countries.

PMID- 7728892
TI  - The spondyloarthropathies.
AB  - The spondyloarthropathies occur with variable frequency in the tropics.
      Ankylosing spondylitis, in particular, is thought to be rare in tropical Africa,
      reflecting a low frequency of the HLA B27 gene. However, in the Melanesian
      populations of Papua New Guinea where there is a relatively high frequency of HLA
      B27, ankylosing spondylosis is infrequent. These diverse observations may be
      related to variations in B27 sub-types. Reactive arthritis is a common and
      important form of acute arthritis in the tropics and in Papua New Guinea at least
      has a strong association with HLA B27. In Africa an increasing prevalence of
      reactive arthritis may be related to the spread of HIV infection. Extra-articular
      features such as balanitis and enthositis are helpful pointers to the diagnosis.
      Disseminated gonococcal infection and tuberculosis must always be considered and
      treatment offered if doubt exists. The mainstay of treatment of reactive
      arthritis is, as always, an anti-inflammatory drug, supplemented by
      hydrocortisone injections; docycline is available for chlamydia-triggered
      arthritis and chloroquine or dapsone for more chronic, unresponsive cases.

PMID- 7728893
TI  - Olfactory toxicity of diethyldithiocarbamate (DDTC) and disulfiram and the
      protective effect of DDTC against the olfactory toxicity of dichlobenil.
AB  - Disulfiram and its breakdown product diethyldithiocarbamate (DDTC) have been
      investigated for their potential to protect against chemically-induced toxicity
      and carcinogenesis because of their inhibitory effects on cytochrome P450 2E1. We
      used DDTC in order to examine the role that cytochrome P450 2E1 plays in the
      bioactivation of beta,beta'-iminodipropionitrile (IDPN) and 2,6
      dichlorobenzonitrile (dichlobenil), resulting in site-specific olfactory lesions
      in the Long-Evans rat and C57B1 mouse. DDTC and disulfiram themselves produced
      olfactory mucosal lesions in the rat, whereas DDTC protected against the
      olfactory toxic effects of dichlobenil in the mouse. A dose-response study
      revealed that approximately twice the dose of DDTC was required in mice to cause
      the same olfactory toxic effects seen in the rat. A study to determine the
      catalytic activity of P450 2E1 by p-nitrophenol (PNP) hydroxylation indicated
      that the Long-Evans rat nasal mucosa is 2.4 times more active than the C57B1
      mouse, which may account for the greater susceptibility of the rat to the
      olfactory toxic effects of DDTC. PNP hydroxylation assays confirmed that DDTC
      decreased P450 2E1 activity in both the rat and mouse liver and nasal mucosa.
      Whereas the results of the mouse study strengthen the hypothesis that dichlobenil
      is bioactivated to a toxic metabolite by cytochrome P450 2E1 in the C57B1 mouse,
      rats pretreated with a marginally toxic dose of DDTC prior to the administration
      of IDPN displayed olfactory mucosal damage, indicating that an alternative or
      additional pathway may be operative in the metabolism of IDPN and/or DDTC.

PMID- 7728894
TI  - Reaction of glutathione with the electrophilic metabolites of 1,1
      dichloroethylene.
AB  - 1,1-Dichloroethylene (DCE) requires cytochrome P450-catalyzed bioactivation to
      electrophilic metabolites (1,1-dichloroethylene oxide, 2-chloroacetyl chloride
      and 2,2-dichloroacetaldehyde) to exert its cytotoxic effects. In this
      investigation, we examined the reactions of these metabolites with glutathione by
      spectroscopic and chromatographic techniques. In view of the extreme reactivity
      of 2-chloroacetyl chloride, primary reactions are likely to include alkylation of
      cytochrome P450, conjugation with GSH to give S-(2-chloroacetyl)-glutathione, or
      hydrolysis to give 2-chloroacetic acid. Our results showed conjugation of GSH
      with 1,1-dichloroethylene oxide, through formation of the mono- and di
      glutathione adducts, 2-S-glutathionyl acetate and 2-(S-glutathionyl) acetyl
      glutathione, respectively. The observed equilibrium constant between the hydrate
      of 2,2-dichloroacetaldehyde and S-(2,2-dichloro-1-hydroxy)ethylglutathione was
      estimated from 1H-NMR experiments to be 14 +/- 2 M-1. Thus, 2,2
      dichloroacetaldehyde is unlikely to make a significant contribution to GSH
      depletion as GSH concentrations above normal physiological levels would be
      necessary to form significant amounts of S-(2,2-dichloro-1
      hydroxy)ethylglutathione. We also compared the formation of the glutathione
      conjugates in rat and mouse liver microsomes using 14C-DCE. The results
      demonstrated a species difference; the total metabolite production was 6-fold
      higher in microsomes from mice, compared with samples from rat. Production of DCE
      metabolites in hepatic microsomes from acetone-pretreated mice was 3-fold higher
      than those from untreated mice suggesting a role for P450 2E1 in DCE
      bioactivation. These results indicate that the epoxide is the major metabolite of
      DCE that is responsible for GSH depletion, suggesting that it may be involved in
      the hepatotoxicity evoked by DCE. Furthermore, this metabolite is formed to a
      greater extent in mouse than in rat liver microsomes and this difference may
      underlie the enhanced susceptibility found in the former species.

PMID- 7728895
TI  - The effects of a soluble-fibre polysaccharide on the adsorption of carcinogens to
      insoluble dietary fibres.
AB  - Epidemiology and animal experiments indicate that dietary fibres protect against
      the development of colorectal cancer. However, insoluble dietary fibres appear to
      be more effective than soluble dietary fibres and one mechanism by which they may
      protect is by adsorbing dietary carcinogens. We found previously that the ability
      of a carcinogen to adsorb in vitro to alpha-cellulose (a model insoluble dietary
      fibre) was strongly related to the hydrophobicity of the carcinogen, measured as
      the calculated logarithm of the partition coefficient between 1-octanol and water
      (C log P). Furthermore, soluble dietary fibres (soluble-fibre polysaccharides),
      including gum arabic, reduced the adsorption of the hydrophobic carcinogen, DNP,
      to alpha-cellulose. In the present study we tested the ability of gum arabic to
      reduce the adsorption in vitro of the carcinogens BaP (C log P = 6.124), DNP (C
      log P = 4.384), and the heterocyclic amines, Trp-P-1 (C log P = 3.230) and MeIQx
      (C log P = 1.078). Gum arabic reduced the adsorption to alpha-cellulose of BaP
      and DNP, but not the adsorption of Trp-P-1 or MeIQx. Gum arabic also reduced the
      adsorption of BaP to an insoluble, dietary-fibre preparation from commercial cork
      which contains the hydrophobic component, suberin, but did not affect the
      adsorption of DNP, Trp-P-1 or MeIQx. It also did not affect the adsorption of DNP
      to an insoluble, dietary-fibre preparation from wheat straw, which contains the
      hydrophobic component, lignin. The results are discussed in terms of hydrophobic
      interactions between carcinogens and insoluble dietary fibres. In vivo, it is
      likely that soluble dietary fibres reduce the adsorption of only highly
      hydrophobic carcinogens to some insoluble dietary fibres.

PMID- 7728896
TI  - Induction of hepatic microsomal drug-metabolizing enzymes by methylsulphonyl
      metabolites of polychlorinated biphenyl congeners in rats.
AB  - The effect of methylsulphonyl (MeSO2) metabolites of 2,3',4',5
      tetrachlorobiphenyl (tetraCB) (IU-70), 2,2',3',4',5-pentachlorobiphenyl (pentaCB)
      (IU-87), 2,2',4',5,5'-pentaCB (IU-101) and 2,2',3',4',5,5'-hexachlorobiphenyl
      (hexaCB) (IU-141), on the hepatic microsomal drug-metabolizing enzyme system was
      investigated in rats. The administration of 3-MeSO2-2,3',4',5-tetraCB (10
      mumol/kg), 3-MeSO2-2,2',3',4',5-pentaCB (0.5 mumol/kg), 3-MeSO2-2,2',4',5,5'
      pentaCB (0.5 mumol/kg) and 3-MeSO2-2,2',3',4',5,5'-hexaCB (2 mumol/kg) to rats
      significantly increased the contents of cytochromes P-450 and b5 and the
      activities of aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and
      benzo[a]pyrene hydroxylase. From these results, it is suggested that the 3-MeSO2
      derivatives studied are possibly potent phenobarbital-like inducers of microsomal
      drug-metabolizing enzymes. On the other hand, 4-MeSO2-2,3',4',5-tetraCB, 4-MeSO2
      2,2',3',4',5-pentaCB, 4-MeSO2-2,2',4',5,5'-pentaCB and 4-MeSO2-2,2',3',4',5,5'
      hexaCB had almost no effect on both cytochrome contents and these enzyme
      activities. After 96 h, following administration of 2,3',4',5-tetraCB,
      2,2',3',4',5-pentaCB, 2,2',4',5,5'-pentaCB and 2,2',3',4',5,5'-hexaCB (342
      mumol/kg each), significant increases in contents of these two cytochromes and in
      activities of these enzymes were observed. The relationship between liver
      concentrations of 3-MeSO2-PCBs after administration of four PCB congeners and
      that after administration of their 3-MeSO2 derivatives, and increases in the
      contents of both cytochromes and activities of drug-metabolizing enzyme suggests
      that the 3-MeSO2 metabolites derived from PCBs studied play an important role in
      the induction of the drug-metabolizing enzymes by the parent PCB congeners.

PMID- 7728897
TI  - Characterization of hepatic microsomal cytochrome P-450 from rats treated with
      methylsulphonyl metabolites of polychlorinated biphenyl congeners.
AB  - The inducing potency of 3-methylsulphonyl(MeSO2)-2,2',4',5,5'-pentachlorobiphenyl
      (pentaCB), which was one of the major MeSO2 metabolites of polychlorinated
      biphenyls (PCBs) present in seal blubber, on the hepatic drug metabolizing enzyme
      activities was examined in comparison with that of the parent compound and
      phenobarbital (PB). The inducing fashion of the above enzymes and changes in the
      contents of PB-inducible P-450 forms by 2,3',4',5-tetrachlorobiphenyl (tetraCB)
      (IU-70), 2,2',3',4',5-pentaCB (IU-87), 2,2',4',5,5'-pentaCB (IU-101) and
      2,2',3',4',5,5'-hexachlorobiphenyl (hexaCB) (IU-141), and their MeSO2 metabolites
      were investigated in rats. Administration at various doses (0.2-1.0 mumol/kg) of
      3-MeSO2-2,2',4',5,5'-pentaCB produced nearly dose-related increases in the
      hepatic concentration of this methyl sulphone, in the contents of cytochromes P
      450 and b5, and in activities of aminopyrine N-demethylase, 7-ethoxycoumarin O
      deethylase and benzo[a]pyrene hydroxylase of liver microsomes. Major PB-inducible
      forms, CYP2B1, CYP2B2, CYP3A2 and CYP2C6 were induced with four PCBs (342
      mumol/kg) and their 3-MeSO2 metabolites (0.5-10 mumol/kg), indicating that 3
      MeSO2 metabolites were strong PB-type inducers of hepatic drug-metabolizing
      enzymes. 3-MeSO2-2,2',4',5,5'-pentaCB was an especially strong inducer. On the
      other hand, four PB-inducible forms of cytochrome P-450 were not induced with the
      4-MeSO2 isomers. The relation between liver concentrations of the corresponding 3
      MeSO2 derivatives and induction of four PB-inducible forms of cytochrome P-450
      after administration of four PCBs and their 3-MeSO2 derivatives further confirmed
      that the 3-MeSO2 metabolites played an important role in the induction which
      parent PCB congeners caused on the hepatic drug-metabolizing enzyme system.

PMID- 7728898
TI  - The influence of 4-alkyl substituents on the formation and reactivity of 2
      methoxy-quinone methides: evidence that extended pi-conjugation dramatically
      stabilizes the quinone methide formed from eugenol.
AB  - The effects of para-alkyl substituents on both the cytochrome P450-catalyzed
      oxidation of phenols to quinone methides (QMs; 4-methylene-2,5-cyclohexadien-1
      ones), and on the rates of nucleophilic additions to the QMs were investigated.
      The derivatives of 4-alkyl-2-methoxyphenol studied were 4-methyl (creosol), 4
      ethyl, 4-propyl, 4-isopropyl, and 4-allyl (eugenol). The relative reactivities of
      QMs derived from these phenols with water were 4-methyl > 4-ethyl = 4-propyl > 4
      isopropyl > 4-allyl. These variations in rate were rationalized by differences in
      stabilization of positive charge density at the site of nucleophilic attack. In
      particular, saturation of the vinyl substituent on eugenol-QM increases the
      solvolysis rate 100-fold. This effect is presumably due to the loss of the
      contribution of an additional aromatic resonance structure to the overall
      resonance hybrid of the QM from 2-methoxy-4-propylphenol. Finally, the kinetic
      results show that there is a 472-fold difference in reactivity within this series
      of QMs. The QM glutathione conjugates were synthesized and characterized by 1H
      NMR and electrospray mass spectrometry and a HPLC assay was developed to quantify
      QM formation in rat liver microsomes. The general trend is increasing alkyl
      substitution at the para position results in more QM; however, in contrast to the
      large range of reactivities of the QMs observed in the kinetic experiments, the
      amounts of P450-derived QM GSH adducts varied only by a factor of 3. In
      particular, similar amounts of the QMs from eugenol and 2-methoxy-4-propylphenol
      were produced which suggests that the lack of reported hepatotoxicity for the
      latter phenol in mice depleted of GSH, may be due to the extreme reactivity of 4
      propyl-QM that would be rapidly detoxified by hydrolysis. These data suggest that
      there may be a threshold cytotoxicity level for QMs related to their reactivity
      which may affect the relative toxicities of 4-alkyl-2-methoxyphenols.

PMID- 7728899
TI  - Glutathione depletion potentiates 12-O-tetradecanoyl phorbol-13-acetate(TPA)
      induced inhibition of gap junctional intercellular communication in WB-F344 rat
      liver epithelial cells: relationship to intracellular oxidative stress.
AB  - Treatment of WB-F344 liver epithelial cells with buthionine sulfoximine (BSO, 100
      microM) for 24 h caused a greater than 95% depletion in cellular glutathione
      (GSH) and potentiated the ability of 12-O-tetradecanoyl phorbol-13-acetate (TPA)
      to inhibit gap junctional intercellular communication (GJIC) between the cells
      (IC50 shifted from 5 microM to 2 microM). Similarly, acute depletion of GSH by up
      to 30%, either with the thiol oxidant diamide or with BSO, also potentiated the
      inhibitory effect of the phorbol ester on GJIC. The treatment of the control
      cells with TPA caused a concomitant increase in the accumulation of oxidation
      products of 2',7'-dichlorofluorescein (DCF), indicating elevated production of
      oxidants in the cells during the blockade of GJIC. The depletion of GSH over a 24
      h period with BSO itself increased the flux of oxidants in the cells but did not
      inhibit GJIC. Treatment of these GSH-depleted cells with TPA caused an additive
      elevation in the accumulation of oxidised DCF metabolites. Direct application of
      H2O2 (25-200 microM) or benzoyl peroxide (25-150 microM) to the control cells for
      60 min caused weak, dose-dependent inhibitions of gap junctional communication in
      these cells but these responses were accompanied by the induction of acute, sub
      lethal cytotoxicity. The depletion of GSH from the cells did not potentiate these
      responses to the peroxides but did facilitate synergistic inhibition of gap
      junctional communication in response to both TPA and sub-toxic doses of either
      peroxide. The results of the above studies indicate that oxidants are produced in
      WB-F344 cells in response to TPA and that these function in a co-operative manner
      with other cellular responses to the phorbol ester in the inhibition of gap
      junctional communication. This may explain why priming the cells for the
      induction of oxidative stress by the depletion of GSH potentiates the inhibitory
      activity of TPA on gap junctional communication.

PMID- 7728900
TI  - Metabolism of 1-nitropyrene in mice: transport across the placenta and mammary
      tissues.
AB  - The distribution and metabolism of the environmental pollutant 1-nitropyrene was
      studied in C57B1/6N mice following oral or intraperitoneal dosing. When
      administered by gavage, 1-nitropyrene and its metabolites demonstrated biphasic
      elimination kinetics from the blood, with half-lives of 0.3 and 1.8 days and a
      distribution volume of 74 ml. Intraperitoneal administration resulted in similar
      biphasic elimination, with half-lives of 0.5 and 3 days and a distribution volume
      of 98 ml. Treating pregnant C57B1/6N (C3H sire) mice by gavage resulted in
      similar absorption and elimination kinetics of 1-nitropyrene and metabolites,
      except that the distribution volume increased to 123 ml. 1-Nitropyrene and/or its
      metabolites (0.7% of the administered dose) crossed the placenta and accumulated
      in the fetuses and amniotic fluid, with both C-oxidized and nitroreduced
      metabolites being detected. Suckling neonates accumulated 1-nitropyrene and its
      metabolites when their dams were administered 1-nitropyrene by gavage. Each
      neonate received approximately 0.1% of the administered dose and demonstrated the
      presence of both C-oxidized and nitroreduced metabolites. These results
      demonstrate that this environmental pollutant is capable of crossing the placenta
      or mammary tissues to expose the offspring to a potentially genotoxic compound.

PMID- 7728901
TI  - STZ-induced diabetes in mice and heme pathway enzymes. Effect of
      allylisopropylacetamide and alpha-tocopherol.
AB  - A frequent coexistence of diabetes and porphyria disease has been reported. Under
      normal conditions, porphyrin biosynthesis is well regulated to only form the
      amount of heme required for the synthesis of the various hemoproteins. The
      activity of some heme enzymes and rhodanese in streptozotocin (STZ) induced
      diabetic mice and in allylisopropylacetamide (AIA) induced experimental acute
      porphyria mice has been examined. The role of alpha-tocopherol (alpha-T),
      reported to prevent protein glycation in vitro, has also been investigated. AIA
      induced hepatic delta-aminolevulinic acid synthetase (ALA-S) activity in control
      animals but was ineffective in the diabetic group. alpha-Tocopherol did not
      modify ALA-S activity in either group. delta-Aminolevulinic acid dehydratase (ALA
      D) and deaminase activities were significantly diminished both in liver and blood
      of diabetic animals. alpha-Tocopherol prevented inhibition of ALA-D, deaminase
      and blood rhodanese activities in diabetic animals but alpha-tocopherol by itself
      did not affect the basal levels of the enzymes studied. The potential use of
      alpha-tocopherol to prevent late complications of diabetes, including the onset
      of a porphyria like syndrome is considered.

PMID- 7728902
TI  - The antioxidant N-acetyl-cysteine protects cultured epithelial cells from
      menadione-induced cytopathology.
AB  - The effects of the antioxidant N-acetyl-cysteine (NAC) were assessed after short
      term exposure of A431 epithelial cells. The drug was able to protect, at least
      partially, the cells from the oxidative stress induced by the quinone menadione.
      In particular, the oxidizing agent-induced cell rounding and detachment from the
      substrate were strongly impaired by pre-exposure to the compound. The mechanism
      of such an effect seems to be ascribable to a target effect of the drug on the
      adhesion properties of the cells. In fact, a modification of morphological
      features of NAC-exposed cells and of their ability to adhere to different coated
      substrates was found. These changes resulted in a significant improvement of the
      A431 tumor cell adhesion pattern which was associated with a noticeable
      rearrangement of some cytoskeletal components, mainly of the microfilament
      system. These data add new importance to the subcellular activity of NAC and seem
      to indicate that the redox status of the cells, i.e. the intracellular balance
      between proxidants and antioxidants, could also play a role in their adhesive
      properties.

PMID- 7728903
TI  - The effect of AT and GC sequence specific minor groove-binding agents on
      restriction endonuclease activity.
AB  - The ability of the naturally occurring A/T specific DNA minor groove binders
      netropsin and diastamycin A and two synthetic G/C selective oligopeptide
      analogues (1 and 2), to interfere with the catalytic activity of restriction
      endonucleases has been investigated. Enzymes were chosen to have A/T rich (EcoRI,
      EcoRV) or G/C rich (BalI, NruI) recognition sequences. An agarose gel assay was
      used to measure the cleavage of 32P-labelled DNA and ligand-DNA binding data was
      obtained using methidium-propyl EDTA footprinting. Netropsin and distamycin bind
      at the recognition sites, and dose-dependently inhibited cleavage by, EcoRI and
      EcoRV, (EcoRI > EcoRV). They were also more effective at inhibiting the catalytic
      activity of BalI than either 1 or 2. NruI was inhibited by distamycin and 2, but
      not by netropsin or 1. DNA footprinting revealed that neither 1 or 2 bound to the
      BalI or NruI recognition sequences under the conditions used whereas netropsin
      and distamycin footprint at adjacent sites. 1 binds to two of the three
      recognition sequences for the enzyme Fnu4HI (GCNGC) in the fragment studied and
      was shown to inhibit DNA cleavage only at these two sites. 2 binds strongly to
      two GGGCTC sequences which are recognition sites for the enzyme BanII. In this
      case a pronounced stimulation of cleavage was observed in the presence of 2 over
      a wide dose range. The results indicate that enzyme inhibition does not
      necessarily result from simultaneous occupancy of a common site, or at nearby
      flanking sequences, and in some circumstances, a pronounced stimulation of enzyme
      cleavage can occur.

PMID- 7728904
TI  - Metallothionein protects DNA from copper-induced but not iron-induced cleavage in
      vitro.
AB  - Iron and copper ions mediate generation of reactive oxygen radicals from O2 and
      H2O2 by the Fenton reaction: these radicals are capable of damaging DNA. We
      studied (a) the ability of these metals to induce double-strand breaks in DNA in
      vitro in the presence of H2O2 and ascorbic acid as donors of reactive oxygen, and
      (b) the ability of the metal-binding protein metallothionein (MT) to protect DNA
      from damage. Strand cleavage was measured by loss of fluorescence after binding
      to ethidium bromide and by increased mobility of DNA in agarose. The results show
      that Cu(II), Fe(II) and Fe(III) all can induce damage to calf thymus DNA under
      our experimental conditions. Cu(II)-induced DNA damage was dose-dependent and the
      degree of damage was proportional to the concentration of H2O2. On the other
      hand, DNA fragmentation was significant only in the presence of high
      concentrations of Fe(II) or Fe(III). Addition of Zn-MT to the reaction mixture
      prior to addition of Cu(II) inhibited fragmentation of DNA in a dose-dependent
      manner but had little effect on iron induced damage. Other proteins (histone or
      albumin) were not effective in protecting DNA from Cu-induced damage, as compared
      to Zn-MT. The formation of Cu(I) from Cu(II) in the presence of hydrogen peroxide
      and ascorbate was also inhibited by addition of Zn-MT. Thus, MT may protect DNA
      from damage by free radicals by sequestering copper and preventing its
      participation in redox reactions.

PMID- 7728905
TI  - Dinitrobenzene induces methemoglobin formation from deoxyhemoglobin in vitro.
AB  - The reaction of hemoglobin (Hb) with dinitrobenzenes (DNBs) was studied to
      develop a molecular-level understanding of such reactions that will enhance the
      development of toxicokinetic models that employ Hb adducts as biomarkers for
      exposure. Methemoglobin (metHb) is formed during the reaction and UV/VIS
      spectroscopy was used to follow the reaction of DNB isomers with deoxy-(dxHb),
      oxy-(HbO2) and carboncarboxy-(HbCO) hemoglobin. HPLC chromatography of dxHb
      treated with radiolabelled DNB was employed to detect possible adduct formation.
      Deconvolution of the spectra and the presence of well-defined isobestic points
      imply that DNB induces a direct conversion of dxHb to metHb, but little or no
      conversion occurs for either HbCO or HbO2. This implies that the reaction of DNB
      with Hb may require direct access to the heme and/or that the reaction is
      initiated by oxidation of the heme, which occurs more readily in the deoxy state.
      Labelled DNB formed no detectable covalent Hb adducts in the presence of dxHb,
      providing evidence that metHb formation is not linked to adduct formation.

PMID- 7728906
TI  - The incorporation of radiolabelled sulphur from captan into protein and its
      impact on a DNA binding study.
AB  - Repeated administration of high doses of captan is known to produce tumours
      specifically in the duodenum of mice. Captan is not carcinogenic in the rat. In
      this study, DNA purified from the liver, stomach, duodenum and jejenum of mice
      dosed with 35S radiolabelled captan was found to contain radioactivity equivalent
      to Covalent Binding Indices in the range 38-91; that from the bone marrow had a
      CBI of 2.8. The distribution of radioactivity between the various tissues did not
      reflect the target organ specificity of captan. Attempts to further purify the
      DNA samples using caesium chloride gradients resulted in partial separation of
      the radioactivity from the DNA suggesting that covalent binding to the DNA may
      not have occurred. A study of the chemical breakdown of captan showed that captan
      is unstable, producing a variety of potentially reactive species containing
      sulphur. Evidence was further obtained to show that the sulphur of captan is
      incorporated into endogenous amino acids and protein. Hepatic DNA from mice dosed
      with 35S radiolabelled N-acetylcysteine, and two thiazolidine derivatives which
      are analogous to known metabolites of captan, was radiolabelled to a similar
      extent to that from captan treated mice. Furthermore, the DNA from each of these
      treatments had similar properties on caesium chloride gradients. It was concluded
      that the radioactivity associated with DNA in the captan DNA binding study was
      present in the low levels of protein which are always associated with purified
      DNA samples.

PMID- 7728907
TI  - The metabolism and DNA binding of the cooked-food mutagen, 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) in precision-cut rat liver slices.
AB  - Precision-cut liver slices prepared from Aroclor 1254 pretreated male rats were
      used to investigate the metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP). The acetyltransferase and sulfotransferase inhibitors,
      pentachlorophenol (PCP) and 2,6-dichloro-4-nitrophenol (DCNP), and the cytochrome
      P450 inhibitor, alpha-naphthoflavone (ANF), were used to modulate PhIP metabolism
      and DNA and protein adduct formation. PCP and DCNP had similar effects on the
      formation of some PhIP metabolites. PCP and DCNP decreased the formation of 4'-(2
      amino-1-methylimidazo[4,5-b]pyrid-6-yl)phenyl sulfate (4'-PhIP-sulfate) and 2
      (hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP)
      glucuronide to 10% and 55% of controls, respectively. 2-Amino-1-methyl-4'-hydroxy
      6-phenylimidazo[4,5-b]pyridine (4'-hydroxy-PhIP) was increased by 50% relative to
      control levels due to PCP and DCNP treatment. PCP and DCNP had different effects
      on the formation of other PhIP metabolites. Metabolite formation as percent of
      control for the uncharacterized metabolite, 'Peak A', was 50% and 100% in
      incubations with PCP and DCNP, respectively. Formation of 4'-hydroxy-PhIP
      glucuronide was decreased to 10% of controls with PCP and increased to 147% of
      controls with DCNP. PCP and DCNP had no effect on the formation of an
      unidentified metabolite, 'Peak B'. ANF decreased metabolite formation by 60-95%.
      None of the enzyme inhibitors had a statistically significant effect on PhIP-DNA
      binding. Covalent binding of PhIP to protein was slightly decreased in
      incubations containing DCNP or PCP. The lack of significant changes in covalent
      binding to either DNA or protein suggests that additional pathways may be
      important in PhIP bioactivation in rat liver slices. With ANF, there was a
      significant decrease (35%) in protein binding. These observations on the effects
      of PCP, DCNP and ANF on PhIP metabolism as well as on covalent binding of PhIP to
      tissue macromolecules are in close agreement with what was reported earlier in
      hepatocytes. This indicates that tissue slices from various target tissues for
      tumorigenesis will be a useful in vitro tool for future studies on heterocyclic
      amine metabolism. This study provides another important example of the utility of
      precision-cut tissue slices to investigate xenobiotic metabolism and toxicity.

PMID- 7728908
TI  - The formation of peroxynitrite in vivo from nitric oxide and superoxide.
AB  - Peroxynitrite is predicted to be formed in vivo from the reaction of nitric oxide
      and superoxide. Nitric oxide at concentrations as low as 3 nM is expected to
      compete efficiently for superoxide near the surface of endothelial cells, based
      on competition kinetics.

PMID- 7728909
TI  - Increased oxidation and decreased conjugation of drugs in the liver caused by
      starvation. Altered metabolism of certain aromatic compounds and acetone.
AB  - Starvation causes several changes in the various processes of biotransformation.
      The focus of this review is on biotransformation of various aromatic and other
      compounds whose metabolism is catalyzed in phase I by isozymes belonging to the
      CYP2E1 gene subfamily, while in phase II phenol-UDPGT or conjugation with GSH
      play a dominant role. The other ways of conjugation are beyond the scope of this
      review. The reason why this aspect has been chosen is that the capacity of these
      reactions is profoundly altered by nutritional conditions. There is a balance
      between the two phases of biotransformation. Therefore, under standard
      circumstances in a well-fed state the intermediate formed in the course of phase
      I is converted to a conjugated compound rapidly, as a result of phase II.
      However, in starvation the pattern of drug metabolism is altered and the balance
      between the two phases is changed. This alteration of drug metabolism upon
      starvation is partly connected to the changes of cofactor supplies due to the
      metabolic state.

PMID- 7728910
TI  - Drug registration in Sri Lanka.

PMID- 7728911
TI  - Immunocontraceptives.

PMID- 7728912
TI  - Maintenance of oxygenation during total intravenous anaesthesia with ketamine
      while breathing air.
AB  - OBJECTIVE: To determine the variation in arterial oxygen saturation during
      intravenous ketamine anaesthesia while breathing air. DESIGN: Prospective study.
      SETTING: General Hospital, Anuradhapura. PATIENTS AND METHOD: 65 patients of both
      sexes between the ages 10 to 60 years scheduled for minor surgery lasting five to
      15 minutes were selected. Anaesthesia was induced with intravenous diazepam and
      ketamine and patients were allowed to breathe air. MEASUREMENTS: Arterial oxygen
      saturation, respiratory rate, degree of analgesia both during and one hour after
      surgery, incidence of nausea, vomiting and hallucinations after recovery were
      recorded. RESULTS: Five patients (7.6%) showed a fall in oxygen saturation to
      less than 90%. Three of them had airway obstruction and the other two were obese.
      Nausea and vomiting occurred in eight patients (12%). Hallucinations were noted
      in five patients (7%). Postoperative analgesia was present one hour after surgery
      in 54 patients (83%). CONCLUSION: Young and otherwise healthy patients maintained
      normal oxygen saturation while breathing air provided airway patency is
      maintained. However, facilities for administration of oxygen, intubation and
      ventilation should be available during ketamine anaesthesia.

PMID- 7728913
TI  - Cardiac dysrhythmias during anaesthesia.
AB  - OBJECTIVE: To determine the incidence of cardiac dysrhythmias during anaesthesia
      and surgery. DESIGN: A prospective study on 500 patients undergoing routine and
      emergency surgery at Sri Jayewardenepura General Hospital. SETTING: Sri
      Jayewardanepura General Hospital. METHOD: Factors that may influence the
      incidence of dysrhythmia such as age, pre-existing heart disease, hypertension
      and anaesthetic technique were noted. Cardiac monitoring was commenced on each
      patient before the induction of anaesthesia and continued up to the recovery
      period. Any dysrhythmia that occurred was noted and a tracing obtained. RESULTS:
      42 patients developed dysrhythmia of whom 21 were nodal rhythms. These occurred
      during maintenance of anaesthesia and needed no treatment. Fourteen patients
      developed ventricular ectopics commonly triggered by intubation. Only one patient
      needed treatment with lignocaine. Sinus bradycardia occurred in 6 patients who
      were treated with intravenous atropine. CONCLUSIONS: Most dysrhythmias seen
      during anaesthesia do not require treatment with specific antiarrhythmic drugs.
      Correcting the cause is often all that is necessary.

PMID- 7728914
TI  - Urinary tract infections in children in a tertiary care service.
AB  - OBJECTIVE: To determine the nature of urinary tract infection (UTI), accompanying
      anomalies and antibiotic sensitivity in children in a tertiary care centre.
      DESIGN: Retrospective observational study. SETTING: King Fahd Hospital of the
      University-Al Khobar. SUBJECTS: Infants and children with proven urinary tract
      infection (UTI). Age up to 12 years seen between 1988-1993. Investigations
      included plain xrays, IVU, voiding cystourethrography and ultrasound examination
      of the abdome. RESULTS: 40% of subjects were referred cases and for the other 60%
      it was the first contact. 56% were infants below 2 years, males were predominant
      and proportion of older children diminished with age. Prominent associated
      anomalies were hypospadias in the male (6.14%), hydronephrosis, prune-belly
      syndrome, renal parenchymal and anorectal anomalies. Organisms predominantly
      grown on culture were Escherichia coli, Klebsiella pneumoniae and enterococci.
      Ampicillin and cotrimoxazole were found to be least effective. CONCLUSIONS:
      Thereapeutic implications for the observations made are important to improve the
      outcome.

PMID- 7728915
TI  - Lipid patterns in patients with chronic occlusive arterial disease affecting
      lower limbs.
AB  - 114 consecutive patients with chronic occlusive arterial disease of lower limbs
      (COADL) had their serum lipid pattern compared with that of 62 controls. 53 had
      abnormal lipids and 36 multiple abnormalities emphasising the common prevalence
      of atherosclerosis among patients with COADL in Sri Lanka. 48.6% of patients
      under 40 years had a lipid abnormality. Smoking and lipid disorders were the main
      risk factors in the under 50 age group. 14 of 16 patients with aortic occlusions
      and five of eight patients under 45 years with iliac disease had lipid disorders.
      21 of 50 patients with femoropopliteal occlusive disease also had lipid
      disorders. A consistent dominant lipid disorder affecting most, was not found.
      Total cholesterol/HDL cholesterol ratio was found to be the commonest
      abnormality. Serum lipid studies are advocated for those with aortoiliac and
      femoropopliteal disease.

PMID- 7728916
TI  - Intravenous immunoglobulin in the treatment of snake bite envenoming: a pilot
      study.
AB  - The standard treatment for snake bite envenoming is with snake antivenon (AVS).
      Reports to date on the efficacy of AVS have been equivocal. Some studies have
      shown a beneficial effect on the coagulopathy, while its effect on neurotoxicity
      is questionable. AVS therapy is also associated with a high incidence of
      reactions. We conducted a pilot study to compare the standard AVS therapy, with
      AVS plus intravenous immunoglobulin (IVIG), in the treatment of snake bite
      evenoming. Our study indicates that the addition of IVIG to the standard AVS
      regimen, eliminates the need to repeat AVS for envenoming associated with
      coagulopathy.

PMID- 7728917
TI  - Acute complete rectal prolapse.

PMID- 7728918
TI  - Treatment of bilateral abductor palsy of the vocal cords by lateralisation of one
      cord.
AB  - Two patients with bilateral abductor vocal cord palsy were treated by
      lateralisation of one cord (1), with two modifications. These modifications have
      not been documented before. The second modification makes the operation more
      suitable for developing countries as an operating microscope is not necessary.
      The surgical procedure is described.

PMID- 7728919
TI  - Medical computing 1.

PMID- 7728920
TI  - Reminiscences: an itinerating medical officer in parangi control.

PMID- 7728921
TI  - The MD or MRCP? ... Improving the quality of postgraduate training programme in
      medicine.

PMID- 7728922
TI  - Cat scratch disease in Sri Lanka.

PMID- 7728923
TI  - First isolation of Vibrio cholerae 0139 (Bengal strain) from a Sri Lankan
      patient.

PMID- 7728924
TI  - Mycoplasma pneumoniae pneumonia.

PMID- 7728925
TI  - Rice and peptide drugs.

PMID- 7728926
TI  - Reaction of (1R,2S,3S)-3-methylcyclohexanediamineplatinum(II) with DNA: isolation
      and characterization of the platinum-nucleotide adducts by means of HPLC and NMR
      spectroscopy.
AB  - Reaction products of calf thymus DNA with (1R,2S,3S)-3
      methylcyclohexanediamineplatinum (abbreviated as Pt(RSS-dach)Cl2) were
      investigated by enzymatic degradation of the platinated DNA and subsequent HPLC
      analysis. Five platinated adducts involving d(GpG), d(ApG) and (dG)2 residues
      were identified by HPLC after complete digestion using deoxyribonuclease I,
      nuclease P1, and alkaline phosphatase. The adducts with d(GpG) and d(ApG)
      consisted of two geometrical isomers, because Pt(RSS-dach)Cl2 lacks a C2 symmetry
      element. The d(GpG) and d(ApG) adducts were intrastrand compounds crosslinked
      between the N7 atoms of the adjacent purine bases. The two d(GpG) adducts were
      most abundant and comprised more than 65% of all the platinated adducts. The
      relative ratio of the two d(GpG) isomers was 3:2 for reaction with DNA, whereas
      the ratio was 1:1 for reaction with a single stranded oligonucleotide. The
      detailed structure of the two d(GpG) adducts is also described based on NMR
      spectroscopic data.

PMID- 7728927
TI  - Enantioselective biotransformation of 1-isopropylnaphthalene in rabbits.
AB  - 1-Isopropylnaphthalene (1) was administered orally to rabbits and the following
      eight metabolites, 2-(1-naphthyl)-2-propanol (7), 2-(1-naphthyl)-1-propanol (8:
      R/S = 83:17), 2-(1-naphthyl)-1,2-propanediol (9:R/S = 40:60), 4-isopropyl-1,2
      naphthoquinone (10), 4-isopropyl-1-naphthol (11), 4-isopropyl-2-naphthol (12), 5
      isopropyl-2-naphthol (13), and 2-(1-naphthyl)propanoic acid (14') as its methyl
      ester (14: R/S = 52:48), were isolated from urine. Among them, three metabolites
      (8, 9, and 14), possessing an asymmetric carbon atom in the molecule, were formed
      enantioselectively and five metabolites (7, 10, 11, 12, and 13) were formed
      regioselectively. The presumed metabolic pathways of 1-isopropylnaphthalene (1)
      in rabbits leading to these metabolites are discussed.

PMID- 7728928
TI  - Studies on metabolites of mycoparasitic fungi. II. Metabolites of Trichoderma
      koningii.
AB  - Four peptaibols, named trichokonins (TKs) V, VI, VII, and VIII, were isolated
      from the culture broth of Trichoderma koningii Oudemans. Primary structures of
      these peptaibols were elucidated by electrospray ionization mass spectrometry
      (ESI-MS), FAB-MS, and collision-induced dissociation (CID) techniques along with
      nuclear Overhauser enhancement spectroscopy (NOESY).

PMID- 7728929
TI  - Non-glutamate type pyrrolo[2,3-d]pyrimidine antifolates. I: Synthesis and
      biological properties of pyrrolo[2,3-d]pyrimidine antifolates containing
      tetrazole congener of glutamic acid.
AB  - Either the alpha- or gamma-carboxyl group of the glutamic acid moiety of N-[4-[3
      (2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5- yl)propyl]benzoyl]-L-glutamic acid
      (1b, TNP-351) and its related compound (1a) was replaced with a 1H-tetrazole
      ring, and the inhibitory effects of the resulting compounds on dihydrofolate
      reductase (DHFR) and the growth of murine fibrosarcoma Meth A cells were
      examined. The gamma-tetrazole analogs (2) were found to be much more potent DHFR
      inhibitors than TNP-351, and strongly inhibited the growth of Meth A cells. On
      the other hand, the alpha-tetrazole analogs (3) were much less active against
      Meth A cells, even though their DHFR-inhibitory activity was comparable to that
      of TNP-351. These findings suggest that the alpha-carboxyl group plays an
      important role in effective uptake via the reduced folate carrier, and a novel
      DHFR inhibitor could be obtained by chemically modifying the gamma-carboxyl
      moiety while leaving the alpha-carboxyl group intact.

PMID- 7728930
TI  - Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase
      inhibition and bronchodilation. V. Thienopyridazinone derivatives.
AB  - Synthesis and pharmacological evaluation of novel thienopyridazinones and related
      compounds are described. A thiophene ring was found to be able to replace the
      benzene ring of a phthalazinone without loss of biological activities. This
      observation supports our hypothesis that the benzene ring plays an important role
      in both thromboxane A2 (TXA2) synthetase-inhibitory and bronchodilatory
      activities. Further, it was shown that the carbonyl moiety of a phthalazinone is
      not necessary for these activities.

PMID- 7728931
TI  - Studies on agents with vasodilator and beta-blocking activities. II.
AB  - A series of phenoxypropanolamines having a hydrazinopyridazinyl moiety was
      synthesized. Their hypotensive and beta-blocking activities were evaluated after
      intravenous administration of the compounds to anesthetized rats. Some of them
      exhibited both activities. In particular, compound 20k is a candidate for
      clinical use due to its hypotensive activity, equal to that of hydralazine, and
      its beta-blocking activity, 2.7-fold more potent than that of propranolol.

PMID- 7728932
TI  - Synthesis and antitumor activity of pyrrolo[2,3-d]pyrimidine antifolates with a
      bridge chain containing a nitrogen atom.
AB  - Novel pyrrolo[2,3-d]pyrimidine antifolates (1a, b and 2a, b) with a nitrogen atom
      in the bridge chain between the 2,4-diaminopyrrolo[2,3-d]pyrimidine and phenylene
      rings were designed and efficiently synthesized. These compounds exhibited more
      potent inhibitory activities than methotrexate (MTX) against the proliferation of
      human epidermoid carcinoma KB cells and human non-small cell lung carcinoma A549
      cells despite their modest dihydrofolate reductase (DHFR)-inhibitory potency.

PMID- 7728933
TI  - Structure of a new peptide, astin J, from Aster tataricus.
AB  - A new peptide called astin J (1) was isolated from the roots of Aster tataricus.
      The structure was elucidated by spectroscopic methods and chemical transformation
      from a cyclic pentapeptide, astin C, isolated from A. tataricus to the analogous
      acyclic peptide, 2. Antileukemic activities of the series of acyclic peptides are
      also described.

PMID- 7728934
TI  - New oral dosage form for elderly patients: preparation and characterization of
      silk fibroin gel.
AB  - The pharmaceutical utility of silk fibroin as a possible material for an oral
      dosage form for elderly patients was investigated. Silk fibroin gel (SFG) was
      prepared from its aqueous solution. The gel formation was studied as a function
      of adjusted pH and concentration of silk fibroin (SF). On the basis of Fourier
      transform infrared spectroscopy of SFG, the transition from the random coil to
      the beta-structure was observed. The rate of gelation was sufficiently
      accelerated by the addition of glycerol to the SF aqueous solution. The glycerol
      content also affected the rate of gelation of the SF solution. Rheological
      properties of SFG were evaluated using a creep meter. The SF content and/or
      glycerol content affected the breaking stress of SFG. Moisture desorption from
      SFG was retarded with an increase in glycerol content. It was found that SFG was
      able to be prepared at room temperature (20 +/- 5 degrees C), and the SF content
      and glycerol content affected the formation and physicochemical properties of
      SFG.

PMID- 7728935
TI  - Evaluation of liposomal erythropoietin prepared with reverse-phase evaporation
      vesicle method by subcutaneous administration in rats.
AB  - We encapsulated erythropoietin (Epo) in dipalmitoylphosphatidylcholine (DPPC)
      liposomes with soybean-derived sterols (SS-liposomes) and its glucoside (SG
      liposomes) by reverse-phase evaporation vesicle method, and evaluated them by
      subcutaneous administration in rats. With 4 min of sonication, the damage to Epo
      activity was observed mainly in the non-encapsulated Epo in the liposomes. This
      study indicated that the bilayer of liposomes had the ability to protect the Epo
      activity, by reducing the aggregation that was caused by interaction between Epo
      molecules. The SG-liposomes had a higher retention of the Epo activity the SS
      liposomes. 25.3% or 33.6% of activity was retained by SS-liposomes under the
      conditions of 4 min or 1 min of sonication, while 53.3% or 58.3% of the activity
      was retained by SG-liposomes under the same conditions. Shorter sonication was
      available to minimize the loss of the Epo activity. Epo in SG-liposomes appeared
      to increase the activity.

PMID- 7728936
TI  - Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase
      inhibition and bronchodilation. VI. Indazole derivatives.
AB  - Synthesis and pharmacological evaluation of novel indazole derivatives are
      described. These compounds were found to exhibit both thromboxane A2 (TXA2)
      synthetase-inhibitory and bronchodilatory activities. This observation supports
      the idea that the partial structure of the 3-pyridyl and phenyl groups with a
      methylene insertion is an important component for well-balanced activities.

PMID- 7728937
TI  - Synthesis and pharmacological effects in mice of halogenated cannabinol
      derivatives.
AB  - Eight halogenated derivatives of cannabinol (CBN) substituted on the aromatic
      ring at the 2 and/or 4 position were synthesized and their pharmacological
      effects were evaluated by intracerebroventricular injection (50 micrograms/mouse)
      in mice, using hypothermia, pentobarbital-induced sleep prolongation, catalepsy
      and anticonvulsant effect as indices. The hypothermic effects of monohalogenated
      derivatives of CBN were comparable to that of CBN, whereas the effects of
      dihalogenated derivatives of CBN except for the fluorinated derivative were
      attenuated. In the interaction with pentobarbital, two monochlorinated
      derivatives exhibited a significant prolongation of sleeping time, although other
      derivatives did not significantly affect the sleeping time. The cataleptogenic
      effects of monofluoro- and 4-bromo-CBN were stronger than that of CBN. 4-Bromo
      CBN exhibited a significant prolongation of seizure latency induced by
      pentylenetetrazol. These data suggest that halogenation of CBN modifies the
      pharmacological profile of the cannabinoid.

PMID- 7728938
TI  - Novel xanthones with superoxide scavenging activity from Garcinia subelliptica.
AB  - Two new xanthones, garciniaxanthone D (1) containing a dihydrobenzofuran ring and
      1,4,5-trihydroxyxanthone (2), have been isolated from Garcinia subelliptica as
      superoxide anion scavengers. Their structures have been determined mainly by
      spectroscopic methods and some chemical reactions.

PMID- 7728939
TI  - E-senegasaponins A and B, Z-senegasaponins A and B, Z-senegins II and III, new
      type inhibitors of ethanol absorption in rats from senegae radix, the roots of
      Polygala senega L. var latifolia Torrey et Gray.
AB  - New inhibitors of ethanol absorption, E-senegasaponins a and b, Z-senegasaponins
      a and b, Z-senegins II and III, were isolated from Senegae Radix, the roots of
      Polygala senega L. var latifolia Torrey et Gray, together with senegins II and
      III. Their chemical structures have been elucidated on the basis of chemical and
      physicochemical evidence, and the geometrical isomeric structures of
      methoxycinnamoyl moiety in each saponin were found to show tautomer-like
      behavior. The inhibitory effects of senegasaponins, senegins, and their related
      compounds have been examined, and some structure-activity relationship have been
      found.

PMID- 7728940
TI  - Catalytic activities and coordination environments of the copper ions in the
      imidazole clusters of histidine-peptides, His(His)nGly and N-acetyl-His(His)nGly
      (n = 3, 8, and 18).
AB  - The copper ions in the imidazole-clusters of histidine-oligopeptide, His(His)nGly
      (n = 18) and N-acetyl-His(His)nGly(n = 8 and 18), showed the d-d transition bands
      at 520 nm and 630 nm and oxidase-like activities. Those with the d-d bands at 480
      nm and 550 nm did not have the activity.

PMID- 7728941
TI  - Taxol and its related taxoids from the needles of Taxus sumatrana.
AB  - Through bioassay-guided separation of the chemical constituents of the needles of
      Taxus sumatrana, taxol (1), cephalomannine (2), and a new taxoid 19-hydroxy-13
      oxobaccatin III (8) have been isolated together with 7-epi-10-deacetyltaxol (3),
      7-epi-10-deacetylcephalomannine (4), baccatin III (5), 19-hydroxybaccatin III
      (6), and 10-deacetyl-13-oxobaccatin III (7). The chemical structure of 8 has been
      elucidated on the bases of its chemical and physicochemical properties.

PMID- 7728942
TI  - Metastasizing tumors in rats treated with alkylating carcinogens.
AB  - Tumors induced in approximately 2000 F344 rats by a number of carcinogenic N
      nitroso compounds have been examined for their propensity to metastasize. The
      objective was to discover relations between the structure of the carcinogen, the
      tumor induced and the proportion of tumors that formed metastases. Treatments
      consisted of multiple doses of one of 16 nitrosamines or 19 alkylnitrosoureas,
      which were administered in drinking water, by gavage or by the intravesicular
      route. Male and female rats were included. Most of the carcinogens were mutagens
      in bacteria, but some were not; this had no bearing on the tendency of induced
      tumors to metastasize, nor did the extent of alkylation of DNA produced in vivo.
      Fewer malignant tumors appeared in the rats treated with nitrosamines than with
      alkylnitrosoureas, but more than twice as many of the former metastasized; many
      were carcinomas or hemangiosarcomas of the liver, of which very few were induced
      by alkylnitrosoureas. Tumors of the liver, lung, mammary gland and forestomach
      metastasized most commonly, whereas those of the esophagus, nasal mucosa, Zymbal
      gland, kidney mesenchyme, thyroid, urinary bladder and mesotheliomas seldom
      formed metastases; none of the tumors of the brain or intestines metastasized; no
      differences between males and females were noted. Some rare tumors, osteosarcomas
      and thymus lymphomas, metastasized frequently. The lungs and lymph nodes were the
      most common sites for metastases, but less frequently liver, heart, kidney,
      adrenal gland, omentum, peritoneum, esophagus and pancreas were involved. Higher
      doses were associated with greater numbers of metastasizing tumors among
      mutagenic or non-mutagenic carcinogens, as has been reported elsewhere. It
      appears that directly alkylating alkylnitrosoureas are no more likely (and
      probably less likely) to induce tumors with metastatic properties than are
      nitrosamines that require metabolic activation to form reactive proximate
      carcinogens.

PMID- 7728943
TI  - The deuterium isotope effect for the alpha-hydroxylation of tamoxifen by rat
      liver microsomes accounts for the reduced genotoxicity of [D5-ethyl]tamoxifen.
AB  - This study describes the application of on line HPLC-electrospray ionization MS
      in the structural determination of the metabolites formed following incubation
      with rat liver microsomes of an equimolar mixture of the anticancer drug
      tamoxifen and its [D5-ethyl]-analogue. The ratio of ca 3:1 between unlabelled and
      D4-labelled alpha-hydroxytamoxifen, indicating a large isotope effect for this
      metabolic process, accounted for the previously observed lower yield of DNA
      adducts formed in the livers of rats treated with D5-tamoxifen compared with
      unlabelled drug. The loss of one deuterium atom on metabolism discriminated
      hydroxyethylated metabolites from others and enabled two further such metabolites
      to be detected, namely alpha-hydroxytamoxifen N-oxide and alpha-hydroxy-N
      desmethyltamoxifen of which the latter is novel. Furthermore, the use of [alpha
      D2-ethyl]- and [beta-D3-ethyl] tamoxifens discriminated alpha- from beta
      hydroxylated metabolites and proved that the metabolites described here were
      alpha-hydroxylated. In contrast to the alpha-hydroxylated metabolites, the other
      metabolites identified, namely tamoxifen N-oxide, N-desmethyltamoxifen, 4
      hydroxytamoxifen and their deuterated counterparts were not depleted in the
      deuterated components. The use of on line HPLC-electrospray ionization MS
      combined with isotopic labelling is a powerful technique for probing the
      structures of metabolites, and, applied to tamoxifen, has provided further
      evidence that alpha-hydroxylation is an important pathway for the conversion of
      the drug into a DNA-reactive metabolite.

PMID- 7728944
TI  - Correlation of (6-4)photoproduct formation with transforming mutations in UV
      irradiated Ha-ras.
AB  - Sites and types of mutations in relation to the amount of cyclobutane pyrimidine
      dimers (CPDs) and (6-4)-photoproducts in UV-irradiated normal Ha-ras sequences
      were investigated. Mouse BALB/C 3T3 cells were transfected with UV-irradiated pYN
      mHras plasmids containing mouse normal Ha-ras sequences, and transformed foci
      developed. Direct DNA sequencing of the Ha-ras retrieved from the foci revealed
      that most mutations (23/24, 96%) took place at dipyrimidine sequences, and the C-
      >T transition at the 3'-cytosine in 5'-TC or 5'-CC sequences was predominant
      (17/24, 71%) in codons 12, 13 and 60. In codon 61, where 5'-TC or 5'-CC is
      absent, two mutations were found at the 5'-TT sequence. More (6-4)photoproducts
      were produced than CPDs in codons 12, 13 and 60, and more CPDs were produced than
      (6-4)photoproducts in codon 61. These results suggest that (6-4)photoproducts are
      the major lesion leading to the mutations in the mouse Ha-ras sequence and
      subsequent transformation of BALB/C 3T3 cells.

PMID- 7728945
TI  - Accumulation of p53 protein in chemically induced oval cells during early stages
      of rodent hepatocarcinogenesis.
AB  - Up to now the possible involvement of p53 in rodent cancerogenesis has been based
      on results of the endpoint of chemically or virally induced carcinogenesis
      tumors. To address the role of altered p53 expression in different stages of the
      multi-step process of rodent carcinogenesis in a systematic way we fed potent
      chemical carcinogens to male rats for 6, for 12 and for 6 weeks followed by a 6
      week recovery period. Assessment of alterations of p53 expression was performed
      by immunoperoxidase staining with a polyclonal antiserum on frozen liver
      sections. Positive p53-immunostaining was localized to treatment-induced
      proliferating oval cells on liver sections of 21/21 2-acetylaminofluorene- (AAF)
      and 19/21 N-nitrosomorpholine (NNM)-treated rats irrespective of application
      scheme as well as to foci of hepatocytes in 1/21 NNM-treated animals and in 3/21
      AAF-treated animals after 6 weeks of treatment only. The induction of oval cell
      proliferation by AAF was more pronounced than by NNM, and for NNM appeared to be
      dependent on application scheme, with a similar lower abundance of oval cells
      after a 6 week treatment with and without recovery as compared to a 12 week
      treatment. These results are discussed with respect to the role of p53 in human
      and rodent carcinogenesis on the one hand, and the disputed function of oval
      cells as facultative liver stem and tumour progenitor cells on the other.

PMID- 7728946
TI  - Simultaneous determination of DNA double strand breaks and DNA fragment size in
      cultured mammalian cells exposed to hydrogen peroxide/histidine or etoposide with
      CHEF electrophoresis.
AB  - A CHEF (contour clamped, homogenous electric field) assay allowing the
      measurement of chemically-generated DNA DSBs (double strand breaks), and the
      simultaneous estimation of the size of the resulting double stranded DNA
      fragments, in a single gel run, has been developed. This method combines a very
      high sensitivity for detecting DNA DSBs with a very good resolution over a broad
      range of megabase--sized DNA. This information can be obtained in a 68 h gel run,
      a time which is slightly elevated as compared to the CHEF DSB assay
      (approximately 20 h), but dramatically reduced as compared to other CHEF
      protocols utilized for resolving DNA fragments of 0.2-5.7 Mb (5-14 days).
      Treatment with 5-10 microM etoposide or 50-100 microM hydrogen peroxide/300
      microM histidine produced DNA fragments with a mean size of 7.7 x 10(5) bp (from
      < or = -0.2 Mb) or 4.6 x 10(6) bp (from > or = 5.7-2.2 Mb), respectively.

PMID- 7728947
TI  - Expression and polymorphism of glutathione S-transferase in human lungs: risk
      factors in smoking-related lung cancer.
AB  - The relationships between smoking and the expression of glutathione S-transferase
      (GST*) isozymes GSTM1-1, GSTM3-3, GSTP1-1 and GSTA1-1/2-2 (GSTA1/2), or between
      smoking and activities of epoxide hydrolase (EH) and aryl hydrocarbon hydroxylase
      (AHH) were investigated in lung samples from 27 patients with lung cancer and 11
      control patients by immunoblot analysis and enzyme assays. Determination of
      genotypes in blood leucocyte DNA showed that possession of the mu-class GSTM1
      gene was closely related to the expression of GSTM1-1 and GSTM3-3 enzymes in lung
      cytosol: patients with the GSTM1 null genotype had no detectable GSTM1 protein
      and less GSTM3 protein than patients with the GSTM1 gene (P < 0.001). Absence of
      the GSTM1 gene did not affect the content of phi-class GSTP1-1 or alpha-class
      GSTA1/2. GST activity towards 1-chloro-2,4-dinitrobenzene was lower (P < 0.01) in
      patients lacking the GSTM1 gene than in those expressing GSTM1; in general,
      patients with a low GSTM3-3, GSTP1-1 or GSTA1/2 content also had significantly
      less overall GST activity. The pulmonary content of GSTP1-1 was greater in cancer
      than in non-cancer patients (P < 0.05). Smoking did not influence the levels of
      GST isozymes or the EH activity. In contrast, the AHH activity was significantly
      (P < 0.01) increased by smoking. Neither AHH nor EH showed a correlation with
      GSTM1 polymorphism. Our data support the idea that in smokers who lack the GSTM1
      gene, activation of carcinogens in tobacco smoke (e.g. benzo[alpha]pyrene) is
      increased, while the efficacy of detoxification is limited both qualitatively
      (absence of GSTM1-1 enzyme and low expression of GSTM3-3 enzyme) and
      quantitatively (low overall GST activity). This imbalance in the metabolism of
      carcinogens may explain the increased susceptibility to lung cancer reported in
      smokers with the GSTM1 null genotype.

PMID- 7728948
TI  - Analysis of mutations induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) in human lymphoblastoid cells.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic aromatic
      amine that is formed in abundance in cooked meats, has been found to be mutagenic
      in human lymphoblastoid TK6 cells at the thymidine kinase and hypoxanthine
      guanine phosphoribosyl transferase (hgprt) loci. The mutations induced at the
      hgprt locus have been analysed. Of the mutations that have been identified, 60%
      were found in the coding sequence of the gene. Forty percent were in the introns
      which resulted in aberrant splicing and consequently, leading to exon losses in
      the mature hprt mRNA. Mutations resulting in a loss of exonIII appeared most
      frequently followed by losses of exonVI, exonVIII and partial loss of exonIX. All
      identified mutations occurred at GC base pairs, consistent with the adducts of
      PhIP that have been found previously and suggesting that the N-(deoxyguanosin-8
      yl)-2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine, (dG-C8-PhIP) adduct may be
      the premutagenic lesion. Most of the mutations are GC-->TA transversions except
      for a cluster of single base pair deletions in a run of guanines. There appears
      to be strand bias in the induction of mutations with 85% of the mutations on the
      non-transcribed strand. Although the number of mutations analysed is limited (54
      mutants), there are several sites (positions 166 and 207 of the coding sequence,
      and the splice acceptor site of exonIII) which are overrepresented. There is a
      preference for a 5' purine but not a strong bias for 3' A as has been found for
      other mutagens that form a premutagenic lesion at G. Triplet analysis shows that
      the triplets, 5'GGA3' and 5'AGG3', where the middle base is mutated are
      preferred.

PMID- 7728949
TI  - Perturbation of hepatocyte nuclear populations induced by iron and
      polychlorinated biphenyls in C57BL/10ScSn mice during carcinogenesis.
AB  - The induction of hepatocarcinogenesis by polychlorinated biphenyls (PCBs) in
      C57BL/10ScSn mice is markedly potentiated by iron. To investigate the effects of
      iron and PCBs on nuclear populations, C57BL/10ScSn mice received a single dose of
      iron-dextran (600 mg Fe/kg) and were fed a diet containing 0.01% of the PCBs
      mixture Aroclor 1254 for up to 6 months. DNA content of isolated nuclei and
      hepatocytes was estimated by flow cytometry. Cell suspensions and nuclei isolated
      from Aroclor treated mice after 6 months contained increased diploid (2N)
      populations compared to controls. In contrast, iron treatment of mice markedly
      enhanced fractions of octoploid (8N) nuclei by 2 weeks and this effect persisted
      over the 6 month period. When Aroclor 1254 and iron were administered together
      there was a synergistic increase in the mononucleated diploid fraction which was
      significant at 2 weeks and highly significant at 6 months. This became the
      predominant nuclear effect. At six months, Aroclor 1254 and iron, both alone and
      in combination, also increased the rate of DNA synthesis in hepatocytes as
      measured by bromodeoxyuridine (BrdU) incorporation. The chronic polyploidizing
      effect of iron overload alone was investigated further and shown to be
      proportional to the dose and was detectable as early as 2 days after 600 mg Fe/kg
      and 1 week after 150 mg Fe/kg. Polyploidization of nuclei was inhibited by the
      oral iron chelator CP94. Iron also induced a prolonged reduction in the incidence
      of binucleated cells. Histologically, nuclear enlargement due to iron was
      confined to the midzonal region of the liver lobule, whereas iron deposition was
      greatest in the periportal region. Iron (600 mg/kg) also caused increased nuclear
      polyploid states in hepatocytes of adult rats and gerbils. Similarly, weanling
      mice with a dominantly diploid cell population, when treated with iron (300
      mg/kg), exhibited a significant shift to a tetraploid (4N) population and a
      marked increase in proliferation as measured by BrdU incorporation and
      proliferative cell nuclear antigen (PCNA) detection. These results indicate that
      Aroclor 1254 and iron induce changes in the mouse hepatocyte population that
      involve 2N and 8N nuclei respectively. The combination treatment leads to the
      emergence and proliferation of a mononucleated, diploid population as observed
      frequently in chemical hepato-carcinogenesis. The reason for the chronic
      polyploidizing effect of iron is unknown, but may imply both increased DNA
      synthesis and impairment of nuclear division with implications in human
      conditions of iron overload.

PMID- 7728950
TI  - In vivo accumulation of 8-hydroxy-2'-deoxyguanosine in DNA correlates with
      release of reactive oxygen species in Fanconi's anaemia families.
AB  - The present study was aimed at verifying the occurrence, if any, of in vivo
      oxidative DNA damage in FA homozygotes, their parents and siblings. 8-Hydroxy-2'
      deoxyguanosine (8-OHdG) was measured, by HPLC/EC, in DNA from circulating blood
      leucocytes from FA homozygotes and their relatives and compared with a group of
      paediatric and adult healthy subjects. The population studied consisted of: (i)
      15 FA homozygotes; (ii) 24 FA heterozygotes; (iii) 11 siblings. The 8-OHdG level
      in FA homozygotes was significantly higher with respect to age-matched controls,
      with a mean level of 33.3 +/- 6.8 (mean +/- SE) and 3.9 +/- 0.26 8-OHdG/10(5) dG
      respectively. The FA parents (heterozygotes) also displayed higher 8-OHdG levels
      relative to controls. The release of hydroxyl (.OH) and .OH-like radicals from
      leucocytes was determined by luminol-dependent chemiluminescence (LDCL) in a
      subgroup of FA homo- and heterozygotes, showing a very large in vivo formation of
      non-superoxide radicals. Chromosomal instability was also measured in the FA
      population. When relating either 8-OHdG or LDCL levels to spontaneous or
      diepoxybutane-induced chromosomal instability (S-CI and DEB-CI respectively), a
      significant correlation was observed between the 8-OHdG, LDCL and S-CI data.
      Within families a positive association was found between 8-OHdG levels in
      homozygotes and their related heterozygotes, suggesting segregation of the
      genetic defect(s) underlying the abnormal oxidative metabolism. The present study
      provides evidence for an in vivo pro-oxidant state in FA, in terms of excess
      formation of .OH and .OH-like radicals, and of DNA hydroxyl adducts. This finding
      appears to be shared by homozygotes and, to a lesser extent, by heterozygotes.

PMID- 7728951
TI  - Transformation reversion induced in JB6 RT101 cells by AP-1 inhibitors.
AB  - The present study was directed to characterizing the reversion of neoplastic
      epidermal JB6 RT101 cells by AP-1 inhibiting drugs. Treatment of tumorigenic JB6
      RT101 cells with retinoic acid (RA), fluocinolone acetonide (FA) or forskolin
      (FN) induced drug dependent (reversible) reversion of transformation. A
      synergistic effect on reversion was found with the three drugs in combination.
      Cells reverted by these three drugs also showed reduced levels of AP-1
      transcription factor activity. After long term exposure of RT101 cells to FA,
      enrichment of flat revertants occurred in the population while a few unreverted
      cells formed foci. These unreverted cells appeared to be FA-resistant. Cloning of
      cells following RA treatment revealed stable reversion at least 2 months after
      drug withdrawal. Stable revertants showed lower basal AP-1 activity than RT101
      cells (P < 0.01) and unstable revertants returned to transformed phenotype and
      elevated AP-1 activity within days following drug withdrawal. To our knowledge
      this is the first demonstration that drug induced reversion co-selects for
      reduced AP-1 activity. These data suggest that the JB6 RT101 cell line is a
      useful cell model for studying reversion of transformation and that inhibition of
      AP-1 activity may be one molecular mechanism of reversion. Considering the
      development of resistance with FA alone and the relative inefficiency of RA or FN
      alone, combinations of the three AP-1 activity inhibitors RA, FA and FN may be
      useful for further animal and clinical studies.

PMID- 7728952
TI  - Chemopreventive effects of calcium but not aspirin supplementation in cholic acid
      promoted colon carcinogenesis: correlation with intermediate endpoints.
AB  - Epidemiological studies have suggested that increased intake of calcium (Ca) or
      aspirin (ASA) is associated with a reduced risk for colon cancer. To delineate a
      possible mechanism of action, the present study used male F344 rats in an
      azoxymethane (AOM)-induced colon tumor model to study the single and interactive
      effects of Ca and ASA on cholic acid-promoted experimental colon carcinogenesis.
      Following initiation with AOM, a promotion diet containing 0.5% cholic acid was
      fed for 34 weeks until the adenoma development stage. Cholic acid was used as a
      surrogate for high-fat diets and to promote carcinogenesis. Diets were
      supplemented with CaCO3 (2% Ca by weight), 250 p.p.m. ASA, or both. After 34
      weeks, the diets were switched during the progression stage and rats were killed
      at week 51. Several intermediate endpoints were examined during the course of AOM
      carcinogenesis to determine their reliability as predictors of colon cancer risk.
      Intermediate endpoints included colon crypt height measurement, colon mucosal
      ornithine decarboxylase (ODC) and colon mucosal protein kinase C (PKC)
      activities. The biomarkers were examined at the beginning of the study at 2
      weeks, and thereafter at 5, 15, 30 and 40 weeks of dietary treatment. Animals
      were necropsied at week 51 and tumor incidence and numbers were analyzed for
      correlation with biomarkers. Survival was highest in the group fed CaCO3 during
      the promotion stage and tumor burden was lowest in groups fed CaCO3 during this
      stage. Supplementation during the progression stage was ineffective. The cholic
      acid promotion model resulted in increased ODC which was inhibited by
      intervention during the promotion stage with Ca, but not ASA. PKC was also
      activated by cholic acid feeding, and this effect was modulated by intervention
      in the promotional stage with Ca or ASA. Colon tumor incidence and burden was
      increased by cholic acid promotion and decreased by Ca, but not affected by ASA.
      In summary, Ca is a more effective chemopreventive agent in cholic acid-promoted
      colon carcinogenesis than ASA, impacting both incidence and tumor number. Colonic
      ODC, but not PKC may be a suitable predictor of risk and response in
      chemoprevention trials for colon cancer.

PMID- 7728953
TI  - Thiol and disulfide metabolites of the radiation protector and potential
      chemopreventive agent WR-2721 are linked to both its anti-cytotoxic and anti
      mutagenic mechanisms of action.
AB  - The ability of the potential chemopreventive agent S-2-(3
      aminopropylamino)ethylphosphorothioic acid (WR-2721) to protect against radiation
      induced mutagenesis at the hprt locus and cell killing was studied using CHO-AA8
      cells incubated for 30 min at 37 degrees C in growth medium containing its active
      thiol 2-[(aminopropyl)amino]ethane-thiol (WR-1065). In parallel experiments, the
      thiol and disulfide forms of the drug present in cells and incubation medium were
      determined in order to identify which, if either, of the components were
      associated with the observed protective effects. Treatment with 4 mM WR-1065
      produced significant intracellular levels of the thiol (WRSH) and disulfide
      (WRSS) forms of the drug, but also caused dramatic elevation of cellular
      glutathione (GSH) and cysteine levels, accompanied by marked protection against
      60Co gamma-photon- and neutron-induced cell killing and mutagenesis. When drug
      treated cells were transferred to drug-free medium and incubated for 4 h at 37
      degrees C, levels of WRSH and WRSS and protection against cell killing decreased
      markedly, whereas levels of GSH and cysteine and protection against mutagenesis
      showed little change. GSH and cysteine levels were not associated with protection
      against radiation-induced mutagenesis, as established by experiments performed
      with buthionine sulfoximine to block GSH synthesis. These data do not support the
      hypothesis that modulation of GSH or cysteine levels by WR-1065 is a major
      mechanism accounting for protection. Protection against mutagenesis was seen for
      cells incubated in medium with concentrations of added WR-1065 as low as 10
      microM, where cellular levels of WRSH and WRSS became difficult to measure (< or
      = 5 microM) and no protection against cell killing was found. An unexpected
      observation was that cells incubated in 40 microM WR-1065 incorporated the drug
      much more rapidly than expected for uptake by passive diffusion and concentrated
      the drug to a marked degree; this indicates that a cell-mediated transport system
      is involved in the uptake of WR-1065 at low drug concentrations.

PMID- 7728954
TI  - Cytotoxicity, DNA adduct formation and DNA repair induced by 2-hydroxyamino-3
      methylimidazo[4,5-f]quinoline and 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5
      b]pyridine in cultured human mammary epithelial cells.
AB  - 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) are heterocyclic amines (HAs) found in cooked
      meats. Both compounds are mammary gland carcinogens in rats. The initiation of
      carcinogenesis by the HAs is believed to be associated with their DNA adduct
      formation that occurs after metabolic activation of the parent amines via
      cytochrome P-450-mediated N-hydroxylation and esterification. To assess the
      capacity of the human mammary epithelium to metabolically activate the HAs, we
      used the 32P-postlabeling method to measure the levels of DNA adducts in a
      culture of human mammary epithelial cells exposed to IQ, PhIP or their N
      hydroxylamine metabolites. Whereas 50 microM parent amines did not form
      detectable levels of DNA adducts in cultured human mammary epithelial cells after
      24 h incubations, concentrations as low as 1 microM N-hydroxylamines produced
      detectable levels of adducts after 2 h incubations. N-Hydroxy-PhIP formed higher
      adduct levels than N-hydroxy-IQ at all concentrations tested. For example,
      following a 2 h incubation at 50 microM, adduct levels (per 10(7) nucleotides)
      were 674 and 16 for N-hydroxy-PhIP and N-hydroxy-IQ, respectively. At similar
      initial adduct levels (10-11/10(7) nucleotides), 60-80% of IQ- and PhIP-DNA
      adducts were removed after 24 h, indicating that the mammary epithelial cell
      culture showed efficient repair of HA adducts. Whereas neither IQ nor PhIP was
      cytotoxic, both N-hydroxy-IQ and N-hydroxy-PhIP were cytotoxic as assessed by a
      dose-dependent inhibition of colony formation. After exposure to 0.1, 1, 10 or 50
      microM N-hydroxy-PhIP (or N-hydroxy-IQ), colony formation was 103 (94), 84 (74),
      37 (29) and 3 (2)% of the control values, respectively. Only N-hydroxy-PhIP (at
      10 and 50 microM), however, was cytotoxic as assessed by the MTT cell survival
      assay (which measures the capacity of mitochondria to metabolize a tetrazolium
      salt). The ability of the N-hydroxylamines to form DNA adducts and to be
      cytotoxic in a culture of human mammary epithelial cells may implicate these
      metabolites as proximate carcinogenic forms of IQ and PhIP in the human mammary
      gland. However, whether there are inter-individual differences in N-hydroxylamine
      metabolism, adduct formation and repair in human mammary epithelial cells
      requires further study. The results from this study support the usefulness of
      cultured human mammary epithelial cells for studies on the genotoxicity and
      metabolism of the N-hydroxylamines of HA food mutagens.

PMID- 7728955
TI  - Early overexpression of cyclin D1 protein in mouse skin carcinogenesis.
AB  - Abnormal expression of cell-cycle regulatory proteins, particularly cyclin D1,
      has been described in human cancers. However, there are few reports of this kind
      in experimental carcinogenesis models, which provide a framework to analyze the
      importance of those alterations in early cancer development. Previous studies
      from our laboratory showed that cyclin D1 mRNA was overexpressed in skin tumors
      generated in SENCAR mice by a two-stage carcinogenesis protocol. In the study
      presented here, immunoprecipitation of fresh tumor samples confirmed the
      overexpression of cyclin D1 protein. We also developed an immunohistochemical
      technique to determine which cells in the lesions overexpressed the cyclin and
      the timing of deregulation during cancer development. Surprisingly, we found that
      all premalignant lesions, including small incipient papillomas, overexpressed
      cyclin D1, whereas normal and hyperproliferative skin were negative. Nuclear
      immunostaining was detected only in the proliferative compartments of the tumors
      and showed an apparent cell-cycle-related variation. These results provide
      evidence for a role of cyclin D1 overexpression in mouse skin carcinogenesis and
      support the use of this model as an alternative to in vitro studies to help
      understand the involvement of cyclin deregulation in cancer development.

PMID- 7728956
TI  - The hepatic metabolism of two carcinogenic dimethylbenz[c]acridines in control
      and induced rats: the distribution and the mutagenicity of metabolites.
AB  - The major and minor metabolites of the potent polycyclic aza-aromatic carcinogens
      7,9-dimethylbenz[c]acridine and 7,10-dimethylbenz[c]acridine, and the
      stereochemistry of the dihydrodiol metabolites have been previously described.
      The metabolite distributions produced in incubations of the aza-aromatic
      compounds with liver microsomes from phenobarbital- and 3-methylcholanthrene
      pretreated and untreated rats, and the mutagenicity in the Ames test are
      described in this paper. The major metabolites of each were the alcohols produced
      by oxidation of the methyl group on the 8,9,10,11-ring for control and
      phenobarbital-induced preparations, while with 3-methylcholanthrene-induced
      preparations both the 7- and 9- (or 10-) monoalcohols were formed. Total
      monofunctionalized dihydrodiol metabolites, the 5,6- and 3,4-isomers for 7,9
      dimethylbenz[c]acridine, and the 3,4-, 5,6- and 8,9-isomers for 7,10
      dimethylbenz[c]acridine, constituted approximately 10% of total metabolites. As
      well, the K-region arene oxide was formed in substantial amounts with both
      compounds, accompanied in the case of 7,10-dimethylbenz[c]acridine with some 8,9
      oxide. When incubations were carried out in the presence of the epoxide hydrase
      inhibitor 3,3,3-trichloropropane-1,2-oxide, dihydrodiol formation was almost
      completely inhibited and relative amounts of both phenols and oxides increased.
      Secondary metabolites were also formed to approximately 10% of the total
      products. The mutagenicity of synthetic alcohols and isolated purified
      metabolites was determined in the Salmonella mammalian microsome plate assay
      (Ames test) with strain TA100. Limited amounts of metabolites isolated precluded
      extensive testing, but high mutagenicities were noted for all 3,4-dihydrodiol
      derivatives isolated. These exceeded those of the parent aza-aromatic
      hydrocarbons. Alcohols were also active but less so than the parent compounds.
      The activation of these two dimethylbenz[c]acridines to mutagens appears to be
      through bay-region diolepoxides following patterns seen in other aza-aromatic
      compounds and the polycyclic aromatic hydrocarbons.

PMID- 7728957
TI  - Chemoprevention of azoxymethane-induced intestinal carcinogenesis by a novel
      synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)
      furanone, in rats.
AB  - The present study was designed to investigate the modifying effects of dietary 5
      hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54), a new synthetic
      retinoidal butenolide, during the post-initiation phase on azoxymethane (AOM)
      induced rat intestinal carcinogenesis. The number of aberrant crypt foci (ACF) in
      rat colon, colonic ornithine decarboxylase (ODC) activity and bromodeoxy-uridine
      (BrdUrd) labeling index in rat colonic epithelium were also assessed. At 7 weeks
      of age, male F344 rats (except the KYN-54 alone and control groups) were given
      weekly s.c. injections of AOM at 15 mg/kg body wt for 3 weeks. Starting 1 week
      after the last injection of AOM, rats (except the control group) were fed a diet
      containing KYN-54 at concentrations of 100 or 200 p.p.m. throughout the
      experiment. All animals were necropsied at 32 weeks after the start of the
      experiment. Compared with the AOM alone group, KYN-54 at both doses reduced the
      incidence and multiplicity of tumors in entire intestine (small and large
      intestines). In the 200 p.p.m. KYN-54 fed group especially, tumor incidence and
      multiplicity in the entire intestine were lower compared with the AOM alone group
      (P < 0.005 and P < 0.05 respectively). Also, the number of ACF/cm2 colon in the
      groups of rats treated with AOM and KYN-54 at both doses were significantly lower
      than that of rats treated with AOM alone (P < 0.05). Colonic ODC activity and
      BrdUrd labeling index in the groups of rats treated with AOM and KYN-54 at both
      doses were slightly lower than those treated with AOM alone. KYN-54 at 200 p.p.m.
      significantly lowered BrdUrd labeling index induced by AOM (P < 0.005). These
      results suggest that KYN-54 might be a promising chemopreventive agent for
      intestinal neoplasia.

PMID- 7728958
TI  - Evidence for in vivo non-mutagenicity of the carcinogen hydrazine sulfate in
      target tissues of lacZ transgenic mice.
AB  - Transgenic mouse models permit the confirmation of in vitro mutagenicity in vivo
      without the constraints in the selection of tissues imposed by other in vivo
      assays. This feature is of particular importance in the determination of
      mutagenicity in the target tissues of carcinogens, especially those that are in
      vitro mutagens. Such information is critical in the determination of whether a
      chemical is carcinogenic via a genotoxic or non-genotoxic mechanism. Hydrazine
      sulfate is an in vitro mutagen that induces lung and liver tumours in mice.
      Transgenic mice from strain 40.6 (Mutamouse) were administered single oral doses
      up to a toxic concentration (400 mg/kg). No dose induced any lacZ mutations in
      lung, liver or bone marrow. Since the highest single dose used is higher than the
      cumulative dose that induced tumours in previous studies, it may be that either
      hydrazine sulfate is genotoxic in target tissues in vivo only when given in
      multiple doses or that it is a non-genotoxic carcinogen.

PMID- 7728959
TI  - The formation of both apurinic/apyrimidinic sites and single-strand breaks by
      chromate and glutathione arises from attack by the same single reactive species
      and is dependent on molecular oxygen.
AB  - The induction of apurinic/apyrimidinic sites (AP sites) and DNA single-strand
      breaks (SSB) by chromate and glutathione in isolated DNA was investigated using
      agents that cleave the DNA at AP sites (putrescine and exonuclease III). It was
      found that chromate/glutathione-induced AP sites contain free aldehyde groups, as
      cleavage by putrescine could be prevented by treatment with sodium borohydride.
      The formation of AP sites and SSB followed a very similar temporal pattern,
      suggesting that both lesions arise from attack by the same single reactive
      species deriving from chromate and glutathione. Furthermore, the induction of
      both lesions was found to be dependent on the presence of molecular oxygen.

PMID- 7728960
TI  - DNA polymerase action on an oligonucleotide containing a site-specifically
      located N-(deoxyguanosin-8-yl)-1-aminopyrene.
AB  - A 25mer oligonucleotide containing a single N-(deoxyguanosin-8-yl-)-1-aminopyrene
      (dGAP), the major DNA adduct formed by reductively activated 1-nitropyrene, was
      synthesized. The adduct was located at nucleotide 21 from the 3' end. DNA
      synthesis on this template by human DNA polymerases alpha and beta, HIV reverse
      transcriptase, Sequenase (version 2.0) and Klenow fragment of DNA polymerase I
      was strongly blocked at the nucleotide 3' to the adduct site. Only when a 3'-->5'
      exonuclease-deficient Klenow fragment was used was incorporation of a nucleotide
      opposite the adduct observed. Nevertheless, extension beyond the adduct site did
      not occur to a significant extent. Only a relatively small proportion of full
      length product (< 5%) was detected. In the presence of Mn2+, the efficiency of
      bypass with this polymerase increased. When a 20mer primer was elongated in the
      presence of only one nucleotide triphosphate, deoxycytidylic acid was
      preferentially incorporated opposite the adduct. Deoxycytidine opposite the
      adduct was also preferred when a set of 21mer primers (containing each of the
      four nucleotides opposite dGAP) were elongated to a full-length product in the
      presence of all four deoxynucleotide triphosphates. In order to confirm these
      results, extension of a 15mer primer was carried out with all four
      deoxynucleotide triphosphates and the products were isolated. Maxam--Gilbert
      sequencing of each elongation product showed that primer extension occurred in an
      error-free manner. We conclude that dGAP is a strong block of DNA replication.
      However, when translesion synthesis occurs, it is largely accurate.

PMID- 7728961
TI  - DNA repair by Ogt alkyltransferase influences EMS mutational specificity.
AB  - Forward mutations induced by ethylmethane sulfonate (EMS) in the lacI gene of
      Escherichia coli were recovered from bacteria proficient or deficient in the
      alkyltransferase encoded by the constitutive ogt gene. EMS doses of 100 or 200 mM
      (Ogt+) and of 50 mM (Ogt-) were selected from the corresponding dose-response
      curves for DNA sequence analysis. A total of 239 induced mutations affecting the
      N-terminal region of the lacI gene were characterized. All mutations were G:C-
      >A:T transitions, consistent with the predominant role of the O6-ethylguanine
      miscoding lesion in mutagenesis by EMS. In the Ogt+ spectrum at the lowest tested
      dose of 100 mM EMS, guanines preceded by an A or T base at the 5' side were on
      average 3.2 times more likely to mutate than those preceded by a G or C base.
      This bias diminished at the higher EMS dose (200 mM) and disappeared in the Ogt-
      genetic background. Previously reported data for Ogt+ bacteria in a Uvr
      proficient background show an opposite bias in favor of mutations at guanines
      preceded by a G or C base. The overall 5' flanking base influence was estimated
      as 8-fold. These data suggest that DNA repair by Ogt alkyltransferase plays an
      important role in the processing of ethylation-induced lesions responsible for GC
      ->AT transitions, influencing their ultimate distribution with respect to
      sequence context. The data further suggest that Ogt and UvrABC excision repair,
      the two major mechanisms of protection against the biological consequences of
      long-chain alkylating agents, show different DNA sequence specificity and that
      the relative importance of these two systems is highly dependent upon the
      chemical dose.

PMID- 7728962
TI  - Cell cyclins and cyclin-dependent kinase activities in mouse mammary tumor
      development.
AB  - Breast cancer in humans, as in mice and rats, is thought to be the result of
      sequential changes in the epithelial cells of the mammalian glands. This study
      examines the altered expression or activation of cell cycle related proteins in
      an in situ system composed of hyperplasia, preneoplasia and neoplasia of mouse
      mammary glands. The results showed a high level of cdc2/cdk2 kinase activities in
      tumors compared to hyperplasias which was independent of cdc2/cdk2 protein
      levels. Some of the cdk-associated proteins which are thought to regulate cdk
      kinase activity were examined in these tissues. Cyclin A was overexpressed in all
      hyperplasias irrespective of their tumorigenic potentials. However, a number of
      alterations in cyclin E protein were associated with cdk2 and its associated
      kinase activity during mammary tumorigenesis. First, the level of normal cyclin E
      (p50) expression was positively correlated with the tumorigenic potentials of
      different hyperplasia lines. Second, several cyclin E isoforms (p48, p43, p35,
      p34, p32) were detected only in tumor tissues. Third, a 2.3- and 8.3-fold
      increase in cyclin E-associated cdk2 kinase activity was present in highly
      tumorigenic hyperplasias and neoplasias respectively compared to the low
      tumorigenic hyperplasias. Polymorphic cell nuclear antigen (PCNA) protein bound
      to cdk2 was a better indicator for cell proliferation and cdk2 kinase activity
      than the PCNA labeling index. These results suggest a sequential pattern of
      multiple derangements in factors regulating cdk2 protein function during mammary
      tumorigenesis. High levels of cdk2 kinase activity are observed only in tumors
      and appear to be closely related to alterations in cyclin E protein expression.

PMID- 7728963
TI  - Role of reactive oxygen in synthetic estrogen induction of hepatocellular
      carcinomas in rats and preventive effect of vitamins.
AB  - We have established an experimental model of oral contraceptive-induced
      hepatocellular carcinomas (HCCs) in female Wistar rats, revealing that
      ethynylestradiol (EE) and norethindrone acetate have actions as both initiators
      and promoters. The present time-sequence study was undertaken to clarify the role
      of free radicals in estrogen induction of HCC by measuring detoxifying enzyme
      activities and levels of 8-hydroxydeoxyguanosine (8-OH-dG) and by assessing the
      effects of concomitant vitamin C, vitamin E or beta-carotene administration on
      hepatocarcinogenesis. During 12 months oral administration of EE (0.075 or 0.75
      mg/day), the 8-OH-dG levels reached peak values after 1 month, when they were
      significantly elevated as compared with the controls. Glutathione peroxidase
      demonstrated a tendency to decrease. Histologically, pre-neoplastic lesions
      assessed by immunohistochemical staining for placental glutathione S-transferase
      (GST-P) were first observed at 2 months in the groups given 0.075 and 0.75 mg/day
      of EE alone, with incidences of HCC at 12 months being 8.7% and 38.5%
      respectively. Combined administration of vitamins with 0.075 mg EE/day reduced
      the elevation of the 8-OH-dG levels. GST-P-positive lesions were first observed
      at 4 months in the vitamin E group and at 6 months in the vitamin C and beta
      carotene groups. As compared with the value in the 0.075 mg EE alone group,
      vitamin administration significantly reduced the numbers of GST-P-positive foci
      after 12 months of treatment. The incidences of HCC at 12 months were 0% in the
      vitamin C group, 4.5% in the vitamin E group and 4.8% in the beta-carotene group,
      i.e. administration of the vitamins inhibited the development of GST-P-positive
      foci, with suppression of HCC. The results thus suggest that free radicals play
      an important role in the induction of HCC by estrogen.

PMID- 7728964
TI  - Formation of 8-hydroxydeoxyguanosine in calf thymus DNA treated in vitro with
      phenylhydroquinone, the major metabolite of O-phenylphenol.
AB  - The generation of 8-hydroxydeoxyguanosine (8OHdG) in calf thymus DNA treated with
      O-phenylphenol (OPP) or its major metabolites, phenylhydroquinone (PHQ) and
      phenylbenzoquinone (PBQ), was studied. The content of 8OHdG residues was
      increased in DNA treated with PHQ, and the generation of 8OHdG was highly
      dependent on PHQ concentration. PBQ had little effect on the formation of 8OHdG,
      and OPP had no effect. The formation of 8OHdG by PHQ was reduced by oxygen
      radical scavengers such as catalase, sodium benzoate and sodium azide. The PHQ
      induced 8OHdG formation was accelerated by the addition of CuCl or CuCl2 to the
      reaction mixture, but was decreased by the addition of chelating agents such as
      EDTA, bathocuproinedisulfonic acid disodium salt (bathocuproine disulfonate) and
      O-phenanthroline. These results demonstrate that hydroxyl radicals generated in
      the process of oxidation of PHQ contribute to the formation of 8OHdG in DNA, and
      copper ions facilitate the oxidative DNA damage. Copper ions greatly accelerated
      the PHQ-induced DNA cleavage in vitro, although they had no effect on cleavage
      without PHQ. On the other hand, DNA cleavage occurred by the addition of FeCl2 in
      the absence and presence of PHQ. FeCl2 stimulates 8OHdG formation only slightly
      with or without PHQ. Furthermore, the stimulatory effect of FeCl2 on 8OHdG
      formation was observed even in the presence of EDTA. The formation of 8OHdG in
      bladder DNA is likely to be one of a series of events leading to bladder tumors
      seen in rats fed OPP-containing diet.

PMID- 7728965
TI  - Hepatocyte growth factor inhibits cell proliferation in vivo of rat
      hepatocellular carcinomas induced by diethylnitrosamine.
AB  - In addition to its mitogenic, motogenic and morphogenic functions on various cell
      types, hepatocyte growth factor (HGF) also suppresses mitosis in several cancer
      cell lines, including carcinomas and sarcomas. Here we report that HGF is also
      mito-inhibitory in rat liver tumors induced by diethylnitrosamine. By using a
      double labeling technique employing [3H]thymidine and 5-bromo-2'-deoxyuridine to
      determine cell proliferation before and after HGF infusion, we determined that
      continuous infusion of 20 micrograms total HGF inhibited tumor cell proliferation
      by 50%. The labeling in non-tumor areas showed the reverse result in that the
      labeling was higher in HGF-treated rats than control rats. These results indicate
      that HGF has different effects on growth of normal and tumorous hepatocytes in
      vivo. These findings may be of relevance in understanding the role of HGF in
      hepatocarcinogenesis and provide added modalities for controlling growth of
      hepatocellular carcinomas.

PMID- 7728966
TI  - The resistant hepatocyte model of carcinogenesis in the rat: the apparent
      independent development of oval cell proliferation and early nodules.
AB  - The early cellular changes in the Solt-Farber resistant hepatocyte model of
      carcinogenesis have been studied to clarify the relationship of oval cell
      proliferation to the development of early hepatocyte nodules. Cellular
      proliferation, intermediate filament profiles and the expression of specific
      cytochrome P450 enzymes were examined. At 24 h after partial hepatectomy (PH)
      many of the bile ductular cells were in S phase, but over the next few days DNA
      synthesis progressively decreased in the portal bile ducts and was more common in
      arborizing ductules (oval cells) radiating from the portal areas. These cells
      strongly expressed cytokeratins 8 and 19 and vimentin, and from 1 week after PH
      they frequently underwent differentiation either into hepatocytes, expressing
      cytochrome P450 enzymes, or into intestinal-type cells. Five days after PH,
      numerous basophilic foci were discernible, and these expanded rapidly. The
      ductular cells swirled around the foci, but their antigenic profile clearly
      indicated that these cells were not involved in the development of these early
      nodules. In normal hepatocytes, cytokeratin 8 immunoreactivity was distinctly
      membranous in location, and could only be readily detected in periportal
      hepatocytes. In the basophilic hepatocyte foci, overexpression of cytokeratin 8
      was consistently associated with cells organizing into acini, with expression
      reminiscent of authentic bile ducts, possibly indicating a structure-function
      relationship. In conclusion, early foci and nodules in this model are derived
      from resistant hepatocytes and not ductular oval cells, the latter being a
      facultative multipotential stem cell compartment.

PMID- 7728967
TI  - In vitro mutational spectrum of cyclopenta[cd]pyrene in the human HPRT gene.
AB  - Cyclopenta[cd]pyrene (CPP) is a widely distributed polycyclic aromatic
      hydrocarbon with potent mutagenic and carcinogenic activity. In order to acquire
      an understanding of the mutagenic pathways of CPP, we studied mutations induced
      by this chemical in human cells. Four independent cultures of a human cell line
      expressing cytochrome P450 CYP1A1 (cell line MCL-5) were treated with CPP, and
      mutants at the hypoxanthine phosphoribosyltransferase (HPRT) locus were selected
      en masse by 6-thioguanine (6TG) resistance. The kinds and positions of the
      mutations were analyzed using the combination of high-fidelity polymerase chain
      reaction (hifi-PCR) and denaturing gradient gel electrophoresis (DGGE). The third
      exon of the HPRT gene was amplified from the 6TG-resistant cells using the hifi
      PCR and the amplified fragment was subsequently analyzed by DGGE to separate
      mutant sequences from the wild-type sequence. Mutant bands were excised from the
      gel, amplified using PCR and sequenced. Sixteen different mutations were
      identified and consisted mostly of the G to T and A to T transversions. Other
      mutations identified included G to A and A to G transitions, a G to C
      transversion, and a single G deletion. Of these mutations, six occurred within a
      run of six guanines. The predominance of transversions involving a guanine or an
      adenine observed with CPP is similar to the data previously reported for the
      racemic mixtures of benzo[a]pyrene (B[a]P), suggesting that the mechanisms of
      mutation induced by CPP may be similar to those induced by B[a]P.

PMID- 7728968
TI  - Effect of cooking temperature on the formation of heterocyclic amines in fried
      meat products and pan residues.
AB  - Frequent consumers of meat have an increased risk of colorectal cancer and
      possibly also of breast, stomach, pancreas and urinary bladder cancer. Bacon,
      'Falusausage', ground beef, meatballs, pork belly, pork chops and sliced beef
      account for more than one-third of the intake of fried meat of the population of
      Stockholm of age 50-75. These dishes were fried at four temperatures (150, 175,
      200 and 225 degrees C) representing normal household cooking practices in
      Stockholm. Heterocyclic amines in these dishes were analysed using solid-phase
      extraction and HPLC. The heterocyclic amines 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino
      3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) were recovered. The formation of IQ was
      favoured by moderate cooking temperatures; IQ was detected in one meat sample
      cooked at 150 degrees C and in some pan residues. The yield of MeIQx, DiMeIQx and
      PhIP increased with the temperature. For several of the meat dishes, the content
      of heterocyclic amines in the pan residue was as large or larger than for
      corresponding piece of meat. The highest levels of MeIQx were 23.7 ng/g in the
      meat and 23.3 ng/g in the pan residue. Corresponding data for DiMeIQx were 2.7
      and 4.1 ng/g and for PhIP 12.7 and 82.4 ng/g. The study leaves little doubt that
      mutagenic heterocyclic amines are ingested by the population of Stockholm, and
      added to previous epidemiological studies from the same area, the combined data
      are consistent with human carcinogenicity of heterocyclic amines. However,
      analytical epidemiological studies are needed before any statement on causality
      can be made.

PMID- 7728969
TI  - The high non-enzymatic conjugation rates of some glutathione S-transferase (GST)
      substrates at high glutathione concentrations.
AB  - Enzymatic properties of five human glutathione S-transferases (GSTs) and non
      enzymatic conjugation rates of GST substrates were examined as a function of
      glutathione (GSH) concentration and pH. GSTP1-1 showed a broad substrate
      specificity with both low and high GSH (10 mM) concentrations at pH 7.0, and the
      inhibitor insensitivity was then prominent. Among the GST substrates tested,
      ethacrynic acid, p-nitrophenylacetate, 1-chloro-2,4-dinitrobenzene and trans-4
      phenyl-3-buten-2-one conjugated nonenzymatically with half-times of 0.39, 3.1,
      9.4 and 10.0 min respectively at 10 mM GSH, pH 7.0 and 35 degrees C. The half
      time for acrolein estimated by extrapolation was approximately 0.5 s. While the
      enzymatic reaction rates were independent of GSH at concentrations larger than Km
      values according to Michaelis-Menten kinetics and relatively insensitive to a pH
      change from 6.5 to 7.0, the non-enzymatic ones were linearly proportional to the
      GSH concentration and sensitive to pH. The enhanced non-enzymatic conjugation of
      various electrophiles at high GSH concentrations may in part account for the
      physiological significance of GSH elevation in preneoplastic and neoplastic
      cells.

PMID- 7728970
TI  - 8-Hydroxyguanine (7,8-dihydro-8-oxoguanine) in hot spots of the c-Ha-ras gene:
      effects of sequence contexts on mutation spectra.
AB  - We previously reported that 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) at the
      second position of codon 12 of the c-Ha-ras gene induces many types of mutations
      in NIH3T3 cells. In this study we incorporated the modified base into the first
      and second positions of codon 12 in the coding strand and into the first position
      of codon 61 in the non-coding strand of the gene using a new 8-hydroxyguanine
      phosphoramidite as a building block during oligonucleotide synthesis. The ras
      genes with 8-hydroxyguanine were transfected into NIH3T3 cells and the mutations
      induced were analyzed. 8-Hydroxyguanine residues at the first positions of codons
      12 and 61 induced mutations to T at the modified sites almost exclusively. On the
      other hand, the DNA lesion at the second position of codon 12 induced a G-->A
      transition in addition to a G-->T transversion, confirming our previous results.
      Mutations in 5'-flanking sites were observed with 8-hydroxyguanine at the second
      position of codon 12 or the first position of codon 61. These results indicate
      that 8-hydroxyguanine in mammalian cells mainly induces a G-->T transversion at
      the modified site, but that other types of mutations are also elicited.

PMID- 7728971
TI  - Mitochondrial enzyme-catalyzed oxidation and reduction reactions of stilbene
      estrogen.
AB  - We have demonstrated for the first time that mitoplasts (i.e. mitochondria
      without outer membrane) were able to convert stilbene estrogen
      (diethylstilbestrol, DES) to reactive metabolites, which covalently bind to
      mitochondrial (mt)DNA. Depending on the cofactor used, mitochondrial enzymes
      catalyzed the oxidation and/or reduction of DES. DES was oxidized to DES quinone
      by peroxide-supported mitochondrial enzyme. A Lineweaver-Burk plot of rate of
      formation of DES quinone at various substrate concentrations yielded a Km of 33
      microM and Vmax of 39 nmol/mg protein/min. The oxidation of DES to DES quinone by
      mitochondria was drastically decreased by known inhibitors of cytochrome P450.
      DES quinone was reduced to DES by mitoplasts in the presence of NADH. The Km and
      Vmax for the DES quinone reduction in the absence of mitoplasts and NADH were 3.2
      microM and 5.6 nmol respectively. The reduction of DES quinone to DES by
      mitoplasts was significantly inhibited by inhibitors of cytochrome b5 reductase
      and diaphorase. DES quinone was also reduced to DES by pure diaphorase, a
      mitochondrial reducing enzyme, in the presence of NADH. The Km and Vmax for the
      DES quinone reduction by diaphorase were 9.0 microM and 4.3 nmol respectively.
      Under reaction conditions similar to oxidation of DES to DES quinone by
      mitoplasts, it was observed that mitochondrial metabolic products of DES were
      able to covalently bind to mtDNA. These data provide direct evidence of
      mitochondrial enzyme-catalyzed oxidation and reduction reactions of DES. In the
      cell, activation of DES in the mitochondria (the organelle in which mtDNA
      synthesis, mtDNA repair and transcription systems are localized) is of utmost
      importance, because an analogous in vivo mitochondrial metabolism of DES through
      covalent modifications in mitochondrial genome may produce instability in the
      mitochondrial genome of the cells. These modifications may in turn play a role in
      the development of DES-induced hepatocarcinogenicity.

PMID- 7728972
TI  - The phorbol ester TPA markedly enhances the binding of calcium to the regulatory
      domain of protein kinase C beta 1 in the presence of phosphatidylserine.
AB  - Activation of protein kinase enzyme activity by Ca2+ and diacylglycerol or
      phorbol esters is a feature of certain isoforms of protein kinase C (PKC).
      Although the binding sites of phorbol ester on the regulatory domain of PKC have
      been extensively studied, little is known about the actual mechanisms of Ca2+
      binding and how this leads to enzyme activation. We previously reported that high
      affinity binding of 45Ca2+ to the regulatory domain of PKC beta 1, expressed as a
      GST fusion protein in Escherichia coli, is dependent on the presence of
      phosphatidylserine (PS) or 12-O-tetradecanoylphorbol-13-acetate (TPA). In the
      present study we have used this system to further analyze Ca2+ binding. Using
      various deletions, we found that different domains in the regulatory domain of
      PKC beta 1 are involved in TPA-induced Ca2+ binding, depending on whether or not
      PS was also present in the binding assay. In addition, Ca2+ binding in the
      presence of TPA alone displayed very different kinetics than Ca2+ binding in the
      presence of TPA and PS. Scatchard analysis indicated that in the presence of TPA,
      the Kd value for Ca2+ binding was 51.9 microM. However, in the presence of both
      TPA and PS, the Kd value dropped to 0.23 microM. These results provide direct
      evidence that TPA activates certain isoforms of PKC by enhancing PS-dependent
      Ca2+ binding, thus decreasing the Kd value for Ca2+ binding to a physiological
      level.

PMID- 7728973
TI  - Glutathione and free amino acids form stable complexes with DNA following
      exposure of intact mammalian cells to chromate.
AB  - Exposure of cells to carcinogenic Cr(VI) compounds results in the formation of
      several types of DNA lesions such as strand breaks, DNA-protein crosslinks and
      uncharacterized DNA-Cr adducts. Hexavalent chromium compounds are positive in
      most bacterial and eukaryotic mutagenic systems, although the nature of DNA
      modifications underlying the chromium-induced mutagenesis is not known.
      Hexavalent chromate(VI) is very active in cellular systems because it is actively
      transported into cells, but intracellularly it is ultimately reduced to Cr(III).
      Here we show that exposure of Chinese hamster ovary (CHO) cells to potassium
      chromate(VI) leads to the formation of stable complexes between DNA and amino
      acids or glutathione. Cysteine, glutamic acid and histidine were the major amino
      acids crosslinked to DNA in chromate-treated cells. Incubation of purified DNA in
      the presence of EDTA dissociated SDS stable amino acid-DNA complexes, which
      indicates that these DNA adducts are most likely to represent ternary
      coordination complexes mediated by Cr(III) rather than covalent linkage between
      amino acids/glutathione and DNA. The amino acids that were found complexed with
      DNA purified from chromate-exposed cells did not orginate from previously
      crosslinked proteins during DNA isolation, but represented authentic reactions of
      free amino acids and glutathione with chromium and DNA in cells. Ternary
      complexes of glutathione or amino acids with Cr(III) and DNA were estimated to
      account for as much as 50% of DNA-bound chromium following exposure to < or = 25
      microM chromate.

PMID- 7728974
TI  - In vitro growth inhibition of neoplastically transformed cells by non-transformed
      cells: requirement for gap junctional intercellular communication.
AB  - We examined whether the inhibition of neoplastically transformed cell growth by
      co-cultured non-transformed cells involved gap junctional intercellular
      communication (GJIC). The growth of poorly communicating (approximately 25-35%
      dye-coupled cells), Ha-ras and neu oncogene-transformed WB-F344 rat liver
      epithelial cells was inhibited by co-culture with highly communicating (90-95%
      dye-coupling), non-transformed WB-F344 cells. Inhibition was dependent upon
      heterologous cell-cell contact and required that the non-transformed cells were
      GJIC competent. GJIC-deficient mutant WB-F344 cells did not suppress transformed
      cell growth. Restoration of mutant cell GJIC by transfection with rat connexin43
      cDNA restored growth-inhibiting activity. These results clearly demonstrate a
      role for GJIC in the inhibition of transformed cell growth by non-transformed
      cells.

PMID- 7728975
TI  - Tyrosine phosphorylation in mouse mammary hyperplasias.
AB  - Tyrosine phosphorylation status was investigated during mouse mammary tumor
      development using non-tumorigenic and tumorigenic hyperplastic outgrowth lines.
      These outgrowth lines were compared with normal mammary glands from pregnant mice
      and with their corresponding tumors. The levels of total tyrosine phosphorylation
      in proteins of hyperplastic and neoplastic tissues were 4.7- and 3.4-fold higher
      than in the normal gland respectively. These results indicate that increases in
      tyrosine phosphorylation occur in the earliest stages of neoplastic development
      and are not restricted to neoplastic cells per se. These results led to the
      identification of the specific proteins showing high levels of tyrosine
      phosphorylation. Of the eight molecular weight bands of proteins exhibiting
      detectable levels of tyrosine phosphorylation, the only proteins exhibiting
      consistently different degrees of phosphorylation between hyperplasias and tumors
      were of approximately 34 kDa. In a series of six different hyperplasias with
      tumorigenic potentials ranging from 0 to 93%, the extent of tyrosine
      phosphorylation of 34 kDa proteins correlated inversely with tumorigenic
      potential. The levels of p34cdc2 and p33cdk2 proteins were examined, using
      antibodies specific for the cdc2 and cdk2 proteins. The amounts of p34cdc2 and
      p33cdk2 proteins were low in non-tumorigenic (TM3 and TM2L) compared to
      tumorigenic hyperplasias and correlated inversely with tyrosine phosphorylation
      of 34 kDa proteins during tumor development. Thus in the non-tumorigenic
      hyperplasias (TM2L and TM3) the majority of p34cdc2 was phosphorylated on
      tyrosine, in contrast to the p34cdc2 in tumorigenic (TM2H) hyperplasias and
      tumors. Two-dimensional PAGE analysis of mammary tumor samples with antibodies
      specific to cdc2, cdk2 and phosphorylated tyrosine revealed one p34cdc2 form, two
      p33cdk2 isoforms and two phosphotyrosine isoforms of about 33-34 kDa. The results
      suggest that the high levels of tyrosine phosphorylation in cdc2 and cdk2 reflect
      the low tumorigenic potential of a subset of mammary preneoplastic hyperplasias.
      This interpretation is in accord with current concepts on the role of tyrosine
      phosphorylation in the regulation of the cyclin-dependent kinases.

PMID- 7728976
TI  - Differences in molecular biological, biological and growth characteristics
      between the immortal and malignant hamster pancreatic cells.
AB  - We compared morphological, biological and molecular biological patterns of a
      newly established, spontaneously immortalized pancreatic ductal cell line, TAKA
      1, with a hamster pancreatic ductal adenocarcinoma cell line, PC-1. PC-1 cells
      grew in a monolayer on plastic tissue culture flasks, whereas TAKA-1 cells
      required type I collagen gel matrix to propagate. The growth rate and
      argyrophilic nuclear organizer region (Ag-NOR) counts were greater in PC-1 cells
      than in TAKA-1 cells. More TAKA-1 cells were in G0/G1 and less were in the S cell
      cycle phase than PC-1 cells. Karyotypically, the consistent change in TAKA-1
      cells was an abnormal no. 3 chromosome, whereas additional chromosomal
      abnormalities were found in PC-1 cells. Ultrastructurally, TAKA-1 cells formed
      ductal structures and were composed of two types of cells, as in the normal
      hamster pancreatic ducts, whereas PC-1 cells were pleomorphic, showed evidence
      for loss of differentiation and contained intracytoplasmic lumens. Unlike the PC
      1, TAKA-1 cells did not show a point mutation at codon 12 in the c-Ki-ras
      oncogene and did not grow in soft agar. Receptor binding assay showed specific
      epidermal growth factor binding to both cell lines, but secretin binding only to
      TAKA-1 cells. Both cells produced and released transforming growth factor-alpha
      in serum-free medium. Both cell lines expressed blood group A antigen, carbonic
      anhydrase, coexpressed cytokeratin and vimentin, and reacted with tomato and
      Phaseolus vulgaris leucoagglutinin (L-PHA) lectins. The results demonstrate that
      chromosomal abnormalities, cell cycle patterns, expression of cytokeratin 18,
      lectin bindings and the c-Ki-ras mutation are the features that distinguish the
      benign from the malignant pancreatic ductal cells in Syrian hamster.

PMID- 7728977
TI  - Chemoprevention by amiloride of experimental carcinogenesis in rat colon induced
      by azoxymethane.
AB  - The effects of amiloride on the incidence and histology of colon tumors induced
      by azoxymethane, on the labeling index of the colon mucosa and on the activity of
      ornithine decarboxylase in the colon wall were investigated in Wistar rats. Rats
      received 10 weekly injections of 7.4 mg/kg body wt azoxymethane and s.c.
      injections of 5 or 7.5 mg/kg body wt amiloride in depot form every other day for
      35 weeks. Prolonged administration of amiloride at a dose of 7.5 mg/kg, but not 5
      mg/kg, significantly reduced the incidence of colon tumors at week 35. However,
      administration of amiloride had little or no significant influence on the
      histological types of colon tumors and cancers. Administration of amiloride at
      7.5 mg/kg significantly decreased the labeling index of the colon mucosa and
      ornithine decarboxylase activity in the colon wall during and after
      administration of azoxymethane. These findings suggest that amiloride inhibits
      development of colon tumors. A possible mechanism of inhibition of colon
      carcinogenesis by amiloride is its suppression of proliferation of colon tumor
      cells.

PMID- 7728978
TI  - Influence of GSTM1 genotype on sister chromatid exchange induction by styrene-7,8
      oxide and 1,2-epoxy-3-butene in cultured human lymphocytes.
AB  - Glutathione S-transferase M1 (GSTM1), catalyzing the conjugation of various
      reactive molecules with glutathione (GSH), shows genetic polymorphism in humans.
      Almost half of all Caucasians lack the GSTM1 gene, being theoretically at a
      higher risk from the toxic effects of substrates for GSTM1. The purpose of the
      present study was to investigate whether the GSTM1 genotype of lymphocyte donors
      influences the in vitro induction of sister chromatid exchanges (SCEs) by styrene
      7,8-oxide (SO) and 1,2-epoxy-3-butene (MEB), the epoxide metabolites of styrene
      and butadiene respectively and potential substrates for GSTM1. SCEs induced after
      a 48 h treatment (started 24 h after culture initiation) by two different
      concentrations of SO (50 and 150 microM) and MEB (50 and 250 microM) were
      analyzed in cultured (72 h) lymphocytes of six GSTM1 null (gene deleted) and six
      GSTM1-positive (gene present) donors. Both SO and MEB were found to clearly
      increase SCEs. The GSTM1 genotype had no influence on SCE induction by SO. In
      contrast, MEB produced a higher level of SCEs among the GSTM1 null than GSTM1
      positive samples. At 250 microM MEB, the GSTM1 null donors showed 31% more
      induced SCEs (on average seven more SCEs per cell) than the GSTM1-positive donors
      (P = 0.02, acetone treatment as the reference). Furthermore, the GSTM1 null
      genotype was associated with a slight decrease in mitotic index and replication
      index, regardless of the treatment. The results suggest that GSTM1-mediated GSH
      conjugation is an important detoxification pathway for MEB, but not for SO, in
      cultured human lymphocytes.

PMID- 7728979
TI  - Induction of a DNA adduct detectable by 32P-postlabeling in the dorsolateral
      prostate of NBL/Cr rats treated with estradiol-17 beta and testosterone.
AB  - Treatment with estradiol-17 beta and testosterone induces epithelial dysplasia
      and, subsequently, adenocarcinoma in the dorsolateral prostate of NBL rats. The
      purpose of this study was to determine whether this carcinogenic effect is
      mediated by genotoxicity. Analogous to adducts produced by estrogens in the male
      hamster kidney, a target of estrogen carcinogenicity, induction of DNA adducts
      detectable by 32P-postlabeling was investigated in the prostate target tissue.
      NBL rats were treated with separate Silastic tubing implants containing
      testosterone and estradiol-17 beta. Control animals received empty implants.
      Animals were killed at 8, 16 and 24 weeks after initiation of treatment, and
      accessory sex glands were sampled for adduct analysis. DNA of the dorsolateral
      and ventral prostate and the coagulating gland (= anterior prostate) was isolated
      and analyzed by nuclease P1-enhancement of the 32P-post-labeling assay. DNA
      adducts were quantitated by Cerenkov counting. An adduct occurred selectively in
      DNA of the dorsolateral prostate of rats treated with estradiol plus testosterone
      for 16 or 24 weeks with relative adduct level values of approximately 10 x 10(9),
      but not in DNA of the ventral or anterior prostate. The adduct was not present in
      DNA of prostate tissue of rats treated for 8 weeks or in DNA of control tissues.
      This adduct was unique with respect to chromatographic location and has not been
      observed before in any tissue of control or hormone-treated animals. Neither the
      structure of the treatment-induced adduct nor the mechanism of its formation is
      known. However, the selective occurrence of this adduct in the tissue of origin
      of the carcinomas and its appearance coinciding with putative preneoplastic
      lesions and preceding carcinoma development suggests a causal relation between
      adduct formation and prostate cancer development in testosterone plus estradiol
      17 beta-treated rats.

PMID- 7728980
TI  - Effects of consumption of brussels sprouts on plasma and urinary glutathione S
      transferase class-alpha and -pi in humans.
AB  - The effects of consumption of glucosinolate-containing Brussels sprouts on plasma
      and urinary glutathione S-transferase (GST) class-alpha and -pi were
      investigated. Five male and five female non-smoking volunteers were randomly
      assigned to two groups in a crossover design. Five persons started on a
      glucosinolate-free diet (control period), while the other five consumed 300 g of
      cooked Brussels sprouts per day, at the expense of 300 g of glucosinolate-free
      vegetables (sprouts period). Dietary regimes were reversed after 1 week. GST
      levels were measured by enzyme-linked immunoabsorbent assay. At the end of the
      sprouts period, a significant increase (1.5-fold) in plasma class-alpha GST
      levels was observed in males but not in females (control versus sprouts, paired t
      test; P-values 0.031 and 0.317 respectively), while plasma GST class-pi levels as
      well as secretion of urinary GST class-alpha and -pi levels remained unchanged.
      We conclude that (i) increased plasma GST class-alpha levels in males originate
      probably solely from the liver and not from stomach, intestine or kidney; (ii)
      males are more susceptible for induction of hepatic GSTs than females; and (iii)
      urinary GST concentration seems less useful as a biomarker for hepatic GST
      induction.

PMID- 7728981
TI  - Enhancement by chronic ethanol intake of N-methyl-N-nitrosourea-induced rat
      mammary tumorigenesis.
AB  - A majority of epidemiological investigations report an association between risk
      for breast cancer in women and alcohol consumption. However, evidence for an
      enhancing effect of ethanol on chemically induced rat mammary tumorigenesis is
      limited and inconsistent. The present study was conducted to evaluate the
      influence of low to high ethanol intakes (15, 20 or 30% of calories) as part of a
      defined, liquid diet on both the initiation and promotion stages of N-methyl-N
      nitrosourea (MNU)-induced rat mammary tumorigenesis. Ethanol consumed by rats at
      15% of calories during either the initiation or promotion stages increased the
      number of mammary adenocarcinomas compared to isocaloric controls. Ethanol intake
      at 20% of calories only during the promotion stage resulted in an increase in the
      number of mammary adenocarcinomas compared to controls. No enhancing effect of
      dietary ethanol at 30% of calories on either stage of tumorigenesis was observed
      in comparison to isocaloric controls. Therefore, ethanol at specific intakes can
      enhance the initiation and promotion stages of MNU-induced rat mammary
      tumorigenesis. There was not, however, a corresponding increase in mammary tumor
      development at the highest intake of ethanol evaluated. Possible reasons for this
      latter lack of effect of ethanol are discussed.

PMID- 7728982
TI  - Transcriptional regulatory and response mapping of the rat Ha-ras upstream
      sequence using primary mammary epithelial cells.
AB  - The rat Ha-ras upstream sequence (-2876 to +986 bp relative to the most 5'
      transcriptional start site) was transcriptionally mapped at a gross level. Ha-ras
      upstream sequence and 5' unidirectional deletion reporter constructs were
      transfected via particle bombardment into primary cultures of rat mammary
      epithelial cells. Analyses of Ha-ras reporter expression show that a fragment
      extending from -2876 to -2110 bp contains a positive regulatory sequence. The
      majority of Ha-ras expression is attributed to this sequence, since its deletion
      results in a 4-fold decrease in expression. The Ha-ras gene was also assessed for
      autoregulation using similar co-transfection experiments. Wild-type and activated
      (codon 12 G-->A transition) Ha-ras expression vectors, transcriptionally driven
      by Ha-ras upstream sequence, were co-transfected with Ha-ras upstream sequence
      deletion reporter constructs. The activated Ha-ras gene product induced its own
      transcription 2-fold, targeting the regulatory region between -2119 and -313 bp.

PMID- 7728983
TI  - Reduction of oxidative DNA-damage in humans by brussels sprouts.
AB  - The effect of consumption of Brussels sprouts on levels of 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG) in human urine was investigated in 10 healthy, male, non
      smoking volunteers. Following a 3 week run-in period, five volunteers continued
      on a diet free of cruciferous vegetables for a subsequent 3 week intervention
      period (control group), while the other five (sprouts group) consumed 300 g of
      cooked Brussels sprouts per day, at the expense of 300 g of a glucosinolate-free
      vegetable. Levels of 8-oxodG in 24 h urine samples were measured by HPLC. In the
      control group there was no difference between the two periods in levels of 8
      oxodG (P = 0.72). In contrast, in the sprouts group the levels of 8-oxodG were
      decreased by 28% during the intervention period (P = 0.039). The present findings
      support the results of epidemiologic studies that consumption of cruciferous
      vegetables may result in a decreased cancer risk.

PMID- 7728984
TI  - On cancer chemoprevention: complications and limitations of some proposed
      strategies.

PMID- 7728985
TI  - Expression, genomic organization, and transcription of the mouse angiotensin II
      type 2 receptor gene.
AB  - Although the rat angiotensin II type 2 receptor (AT2) was cloned and shown to be
      a member of the seven transmembrane domain-type receptor family, its signaling
      mechanism and biological roles have not been established. To acquire additional
      information on the structure and functions of AT2 genomic DNA, we cloned the
      mouse AT2 gene and examined its expression, transcription, and genomic
      organization. The amino acid sequence of the mouse AT2 cDNA showed a 98.5%
      sequence identity with the rat AT2. In mouse fetus, mRNA of the AT2 was highly
      expressed in the eviscerated carcass and brain. This expression decreased rapidly
      after birth. In 10-week-old mice, mRNA of the AT2 could be detected in the brain
      by Northern blot analysis. However, reverse transcription-polymerase chain
      reaction showed that mRNA of the AT2 was expressed in all organs examined,
      indicating that the AT2 is expressed at a low level in other organs. Southern
      blot analysis of the genomic DNA of the mouse liver digested with BamHI, EcoRI,
      and HindIII resulted in single bands, indicating that the AT2 gene probably
      exists at a single locus in the mouse genome. The nucleotide sequence of the AT2
      gene (4.5 kb of the EcoRI fragment) revealed the presence of three exons. An
      entire coding sequence was included in the third exon. Primer extension
      experiments showed the presence of two transcription initiation sites in the
      mouse AT2 gene. A DNA segment of about 1.5 kb of the promoter region (-1497 to
      +56 bp) of the mouse AT2 gene was fused to a luciferase reporter gene.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7728986
TI  - In vivo adenovirus-mediated gene transfer via the pulmonary artery of rats.
AB  - Gene transfer into the pulmonary vasculature has the potential to be a powerful
      technique for both investigation of pulmonary pathophysiology and development of
      genetic therapies for pulmonary vascular disease. To evaluate the potential for
      in vivo pulmonary arterial gene transfer, we infused adenoviral vectors into the
      left pulmonary artery of Sprague-Dawley and cotton rats. Access to the left
      pulmonary artery was obtained by a percutaneous transcatheter approach or through
      thoracotomy and pulmonary arteriotomy. With the thoracotomy approach, both
      pulmonary arterial inflow and pulmonary venous outflow were occluded during
      vector influsion and throughout a subsequent 20-minute dwell period. The success
      of gene transfer was assessed by staining for evidence of recombinant gene
      expression in lungs excised at time points ranging from 48 to 72 hours after
      virus infusion. With the thoracotomy technique, pulmonary gene transfer was
      successful in 15% of surviving Sprague-Dawley rats and 30% of surviving cotton
      rats. Percutaneous catheter-based pulmonary gene transfer was not successful. In
      rats with pulmonary gene transfer, 1% to 8% of total left lung cells expressed
      the recombinant gene. Recombinant gene expression was found in endothelial cells
      (0.2% to 18% of total transduced cells), smooth muscle cells (0% to 3%),
      macrophages (1% to 7%), airway epithelial cells (2% to 50%), and alveolar
      epithelial cells (38% to 94%). Investigation of the low rate of successful gene
      transfer in individual animals suggested that insufficient physical contact
      between the virions and pulmonary cells was the most likely cause. In vivo gene
      transfer into the rat pulmonary vasculature can be accomplished with adenovirus
      vectors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728987
TI  - Myosin heavy chain expression in contracting myocytes isolated during embryonic
      stem cell cardiogenesis.
AB  - Mouse embryonic stem (ES) cells are totipotent cells derived from the inner cell
      mass of the preimplantation blastocyst and are capable of differentiating in
      vitro into cardiac myocytes. Attached cultures of differentiating ES cells were
      established to document the timing of contractile development by microscopic
      observation and to permit the microdissection of cardiac myocytes from culture.
      The onset of spontaneous contraction varied markedly in differentiation culture,
      with contraction being maintained on average for 9 days (range, 1 to 75 days).
      Indirect immunofluorescence in microscopy showed that myosin expression was
      localized to the contracting cardiac myocytes in culture. Myosin heavy chain
      (MHC) isoform expression in microdissected ES cell-derived cardiac myocytes was
      determined by means of sodium dodecyl sulfate-polyacryl-amide gel
      electrophoresis. The distribution of MHC isoform expression in isolated ES cell
      cardiac myocytes was as follows: 27% expressed the beta-MHC isoform, 33%
      expressed both the alpha- and beta-MHC isoforms, and 40% expressed the alpha-MHC
      isoform. MHC phenotype was correlated to the duration of continuous contractile
      activity of the myocytes. Myocytes that had just initiated spontaneous
      contractile activity predominantly expressed the beta-MHC (average days of
      contraction before isolation, 2.5 +/- 0.7). The alpha-MHC isoform was detected
      after mouse prolonged contractile activity in vitro (1 to 5 weeks). A strong
      correlation was obtained between MHC phenotype and days of contraction of the
      cardiac myocyte preparations isolated from ES cell cultures (r = .93). The
      apparent transition in MHC isoform expression during ES cell differentiation
      parallels the beta- to alpha-MHC isoform transition characteristic of murine
      cardiac development in vivo. These findings are evidence that ES cell cardiac
      myocyte differentiation follows the normal developmental program of murine
      cardiogenesis.

PMID- 7728988
TI  - Myosin light chain-actin interaction regulates cardiac contractility.
AB  - The amino-terminal domain of the essential myosin light chain (MLC-1) binds to
      the carboxy terminus of the actin molecule. We studied the functional role of
      this interaction by two approaches: first, incubation of intact and chemically
      skinned human heart fibers with synthetic peptide corresponding to the sequences
      5 through 14 (P5-14), 5 through 8 (P5-8), and 5 through 10 (P5-10) of the human
      ventricular MLC-1 (VLC-1) to saturate actin-binding sites, and second, incubation
      of skinned human heart fibers with a monoclonal antibody (MabVLC-1) raised
      against the actin-interacting N-terminal domain of human VLC-1 using P5-14 as
      antigen to deteriorate VLC-1 binding to actin. P5-14 increased isometric tension
      generation of skinned human heart fibers at both submaximal and maximal Ca2+
      activation, the maximal effective peptide dosage being in the nanomolar range. A
      scrambled peptide of P5-14 with random sequence had no effects up to 10(-8)
      mol/L, ie, where P5-14 was maximally effective. P5-8 and P5-10 increased
      isometric force to the same extent as P5-14, but micromolar concentrations were
      required. Amplitude of isometric twitch contraction, rate of tension development,
      rate of relaxation, and shortening velocity at near-zero load of electrically
      driven intact human atrial fibers increased significantly on incubation with P5
      14. These alterations were not associated with modulation of intracellular Ca2+
      transients as monitored by fura 2 fluorescence measurements. Incubation of
      skinned human heart fibers with MabVLC-1 increased isometric tension at both
      submaximal and maximal Ca2+ activation levels, having a maximal effective
      concentration in the femtomolar range.

PMID- 7728989
TI  - Protein kinase A does not alter economy of force maintenance in skinned rat
      cardiac trabeculae.
AB  - Recent mechanical, biochemical, and energetic experiments have suggested that
      catecholamines may increase the cycling rate of cross-bridges independent of
      changes inn intracellular calcium. An increased rate of cross-bridge cycling is
      expected to result in decreased economy of force maintenance. The present study
      tested this hypothesis directly by measuring the rate of ATP consumption in
      skinned cardiac trabeculae as a function of steady state force. Rat cardiac
      trabeculae were skinned with Triton X-100. Resting sarcomere length was measured
      by laser diffraction, and ATP consumption was assessed by an enzyme-coupled
      optical technique. Force-[Ca2+] relations were fit to a modified Hill equation.
      Force dependency of the rate of ATP consumption was analyzed by multiple linear
      regression analysis. beta-Adrenergic stimulation was mimicked by incubation of
      the skinned muscle preparation with the catalytic subunit of protein kinase A
      (PKA). Treatment with PKA (3 micrograms/mL, 40 minutes) induced a significant (65
      +/- 23%, P = .01) increase in [Ca2+] required for half-maximal steady state
      force, whereas the steepness of the force-[Ca2+] relation was not affected. The
      rate of ATP consumption was linearly correlated with steady state force,
      regardless of PKA treatment status (P < .001). However, neither the slope nor the
      intercept was affected by PKA treatment. Hence, PKA treatment did not affect
      either the maximum rate of ATP consumption or the economy of force maintenance.
      These results suggest that beta-adrenergic stimulation does not alter the rate
      limiting step of cross-bridge cycling during isometric contraction in myocardium.

PMID- 7728990
TI  - A retinoic acid-induced clonal cell line derived from multipotential P19
      embryonal carcinoma cells expresses smooth muscle characteristics.
AB  - Despite intense interest in understanding the differentiation of vascular smooth
      muscle, very little is known about the cellular and molecular mechanisms that
      control differentiation of this cell type. Progress in this field has been
      hampered by the lack of an inducible in vitro system for study of the early steps
      of smooth muscle differentiation. In this study, we describe a model system in
      which multipotential mouse P19 embryonal carcinoma cells (P19s) can be induced to
      express multiple characteristics of differentiated smooth muscle. Treatment of
      P19s with retinoic acid was associated with profound changes in cell morphology
      and with the appearance at high frequency of smooth muscle alpha-actin-positive
      cells that were absent or present at extremely low frequency in parental P19s. A
      clonal line derived from retinoic acid-treated P19s (9E11G) stably expressed
      multiple characteristics of differentiated smooth muscle, including smooth muscle
      specific isoforms of alpha-actin and myosin heavy chain, as well as functional
      responses to the contractile agonists phenylephrine, angiotensin II, ATP,
      bradykinin, histamine, platelet-derived growth factor (PDGF)-AA, and PDGF-BB.
      Additionally, 9E11G cells expressed transcripts for MHox, a muscle homeobox gene
      expressed in smooth, cardiac, and skeletal muscles, but not the skeletal muscle
      specific regulatory factors, MyoD and myogenin. Results demonstrate that retinoic
      acid treatment of multipotential P19 cells is associated with formation of cell
      lines that stably express multiple properties of differentiated smooth
      muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728991
TI  - Induction of monocyte chemoattractant protein-1 synthesis in human monocytes
      during transendothelial migration in vitro.
AB  - Monocyte chemoattractant protein-1 (MCP-1, or monocyte chemotactic and activating
      factor) plays important roles in the recruitment of monocytes and thus in the
      development of atherosclerosis. In this study, we determined whether MCP-1
      synthesis was induced by the cellular interaction between monocytes and
      endothelial cells during the process of transendothelial migration. We found that
      when human peripheral blood monocytes (2.5 x 10(6) cells) and umbilical vein
      endothelial cells (HUVECs; 5.0 x 10(5) cells) were cocultured for 5 hours, 7.9
      ng/mL MCP-1 was secreted into the medium, whereas when the two were cultured
      separately, MCP-1 levels were 1.0 and 0.9 ng/mL, respectively. Furthermore, the
      use of interleukin-1 beta (IL-1 beta)-pretreated HUVECs in cocultures induced
      twice the levels of MCP-1 as in unstimulated HUVEC culture. Conditioned medium
      had transendothelial chemotactic activity for monocytes, and this activity was
      completely abolished by addition of anti-MCP-1 antibody. Although MCP-1 mRNA
      levels were very low or undetectable in HUVECs or monocytes alone, message could
      be detected after 2 hours of coculture in total mRNA preparations from both
      monocytes and HUVECs. mRNA levels increased by 4 hours and had declined slightly
      by 24 hours. The rapid induction of message suggests that cell contact between
      monocytes and HUVECs induces the de novo synthesis of MCP-1 protein. Anti
      interleukin (IL)-1 alpha/beta and anti-tumor necrosis factor-alpha antibodies, or
      anti-lymphocyte function-associated antigen-1 and very late antigen-4 antibodies,
      had little or no inhibitory effects on MCP-1 secretion by cocultures.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7728992
TI  - Regulation of vascular endothelial growth factor in cardiac myocytes.
AB  - Collateral blood vessels supplement normal coronary blood flow and coronary blood
      flow compromised by coronary artery disease, thereby protecting the myocardium
      from ischemia. Collateral vessel formation is the result of angiogenesis.
      Vascular endothelial growth factor (VEGF), also known as vascular permeability
      factor (VPF), is a secreted mitogen specific for endothelial cells and an
      extremely potent angiogenic factor. In the present study, VPF/VEGF mRNA and
      protein were demonstrated to be markedly stimulated in primary rat cardiac
      myocytes in vitro in response to reduction of the oxygen tension to 1% or
      inhibition of the electron transport chain. Four isoforms of VPF/VEGF were
      coordinately regulated by hypoxia, including a novel isoform not previously
      described. Phorbol ester and the depolarizing agent veratridine, stimulators of
      protein kinase C and calcium influx, respectively, were found to markedly
      increase VPF/VEGF mRNA expression in cardiac myocytes. Forskolin, a potent
      stimulator of adenylate cyclase, produced a small but significant increase in
      VPF/VEGF mRNA expression in the cardiac myocytes. However, only H7, an inhibitor
      of protein kinase C, inhibited the hypoxic induction of VPF/VEGF mRNA; inhibitors
      of calcium influx and the calcium-calmodulin-dependent protein kinase II as well
      as inhibition of protein kinase A did not block the hypoxic induction of VPF/VEGF
      mRNA. This suggests that more than one signal transduction pathway is involved in
      regulating VPF/VEGF expression. The sensor that regulates the expression of
      hypoxia-responsive genes has been proposed to be a heme protein. Consistent with
      this model, transition metals initiate a genetic program similar to
      hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728993
TI  - Increased in vivo expression and production of endothelin-1 by porcine
      cardiomyocytes subjected to ischemia.
AB  - Circulating levels of the endothelium-derived vasoconstrictor peptide endothelin
      1 (ET-1) are increased in association with myocardial ischemia and infarction.
      The present study investigates whether ET-1 is synthesized and produced locally
      in the ischemic heart. Sixteen pigs were divided into three groups. In the first
      group, the left anterior descending coronary artery was occluded for 90 minutes,
      followed by 150 minutes of reperfusion (group A, n = 8). Two additional groups
      were subjected to 90 minutes (group B, n = 4) or 240 minutes (group C, n = 4) of
      ischemia without reperfusion. Biopsies from the nonischemic and ischemic
      myocardium were rapidly obtained from the beating heart and subsequently examined
      by Northern blot, in situ hybridization, and immunohistochemistry. Arterial
      plasma ET-1 was measured before ischemia and at the end of the experiments.
      Northern blot revealed a twofold increase in ET-1 mRNA in the ischemic myocardium
      compared with the nonischemic myocardium. In situ hybridization showed a
      considerable increase in ET-1 mRNA over the ischemic cardiomyocytes. Substantial
      ET-1-like immunoreactivity (ET-1-ir) was detected in cardiomyocytes in the
      ischemic region. In contrast, little or no ET-1-ir or mRNA was detected in
      nonischemic cardiomyocytes. Both in the ischemic and nonischemic regions, little
      ET-1-ir was detected in vascular endothelial cells or vascular smooth muscle
      cells. There was no difference in the intensity and distribution of ET-1 mRNA
      expression or ET-1-ir among experimental groups A, B, and C. Arterial plasma ET-1
      was increased only in group A, the reperfused group.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7728994
TI  - Characterization of bradykinin B2 receptors in adult myocardium and neonatal rat
      cardiomyocytes.
AB  - Specific [125I-Tyr8]bradykinin (BK) binding was observed on myocardial membranes
      from adult guinea pigs, dogs, rats, and rabbits that was displaced by unlabeled
      BK with an IC50 between 0.1 and 30 nmol/L. In the adult guinea pig ventricular
      myocardium, which displays both high- and low-affinity binding, guanosine 5'-O-(3
      thiotriphosphate) (GTP gamma S; 100 mumol/L) eliminated high-affinity binding and
      reduced total specific [2,3-prolyl-3,4-3H(N)]BK ([3H]BK) binding by > 60%.
      Agonist competition binding to rat myocardial membranes was characterized as
      being of one affinity for BK in the nanomolar range, and it was not altered by
      GTP gamma S. Saturation binding studies with [125I-Tyr8]BK and [3H]BK, performed
      on cultured neonatal rat cardiac myocytes, revealed a single class of BK binding
      sites with a Kd and Bmax of 0.24 +/- 0.04 nmol/L and 18.4 +/- 1.1 fmol/mg
      protein, respectively (approximately 1500 receptors per cell). In competitive
      binding assays, unlabeled BK, Hoe 140 (a specific BK B2 receptor antagonist), and
      des-Arg9,[Leu8]BK (a BK B1 receptor antagonist) displaced [125I-Tyr8]BK with an
      IC50 of 4.3, 0.041, and 307 nmol/L, respectively. In the presence of 100 mumol/L
      GTP gamma S, [3H]BK binding to myocyte membranes was reduced by 40%, but the IC50
      did not change. Cardiac fibroblasts, evaluated in parallel to the myocytes,
      contain a single class of [3H]BK binding sites (248 +/- 72 fmol/mg) with a 130
      fold lower relative affinity (32.4 +/- 11.3 nmol/L) than that determined in rat
      cardiomyocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728995
TI  - Calcium sensitivity of isometric tension is increased in canine experimental
      heart failure.
AB  - To examine the role of alterations in myofibrillar function in chronic heart
      failure, we determined isometric tension-pCa relations in permeabilized
      myocardium from a canine model of dilated cardiomyopathy (DCM) produced by
      chronic rapid pacing. In the initial series of experiments, seven dogs were paced
      at 250 beats per minute for 28.9 +/- 7.0 days, resulting in ventricular
      dilatation and reduced ejection fractions by echocardiography and elevated
      intracardiac filling pressures. Isometric tension-pCa relations were measured by
      using mechanically disrupted and permeabilized myocyte-sized preparations
      obtained from left ventricular biopsies before (n = 11) and after (n = 10)
      chronic rapid pacing-induced heart failure. Resting sarcomere length (SL) was set
      at 2.35 microns, and preparations had low end compliance (SL was 2.23 +/- 0.03
      microns during maximal activation). Passive tension (2.1 +/- 1.0 versus 2.4 +/-
      0.6 mN/mm2) and maximal Ca(2+)-activated tension (25.9 +/- 9.3 versus 27.8 +/-
      6.8 mN/mm2) were similar for control and DCM preparations, respectively. However,
      the calcium sensitivity of isometric tension was increased in failing myocardium
      (pCa50 5.95 +/- 0.11 [DCM] versus 5.83 +/- 0.10 [control], P = .001). Treatment
      of myofibrillar preparations with the catalytic subunit of protein kinase A
      decreased calcium sensitivity of tension to a greater degree in failing
      preparations (shift of pCa50 from 6.04 +/- 0.06 to 5.75 +/- 0.09, n = 7) than in
      nonfailing preparations (5.91 +/- 0.08 to 5.74 +/- 0.07, n = 8), and isometric
      tension-pCa relations in the two groups were not significantly different after
      protein kinase A treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7728996
TI  - Effects of action potential duration on excitation-contraction coupling in rat
      ventricular myocytes. Action potential voltage-clamp measurements.
AB  - Although each of the fundamental processes involved in excitation-contraction
      coupling in mammalian heart has been identified, many quantitative details remain
      unclear. The initial goal of our experiments was to measure both the
      transmembrane Ca2+ current, which triggers contraction, and the Ca2+ extrusion
      due to Na(+)-Ca2+ exchange in a single ventricular myocyte. An action potential
      waveform was used as the command for the voltage-clamp circuit, and the membrane
      potential, membrane current, [Ca2+]i, and contraction (unloaded cell shortening)
      were monitored simultaneously. Ca(2+)-dependent membrane current during an action
      potential consists of two components: (1) Ca2+ influx through L-type Ca2+
      channels (ICa-L) during the plateau of the action potential and (2) a slow inward
      tail current that develops during repolarization negative to approximately -25 mV
      and continues during diastole. This slow inward tail current can be abolished
      completely by replacement of extracellular Na+ with Li+, suggesting that it is
      due to electrogenic Na(+)-Ca2+ exchange. In agreement with this, the net charge
      movement corresponding to the inward component of the Ca(2+)-dependent current
      (ICa-L) was approximately twice that during the slow inward tail current, a
      finding that is predicted by a scheme in which the Ca2+ that enters during ICa is
      extruded during diastole by a 3 Na(+)-1 Ca2+ electrogenic exchanger. Action
      potential duration is known to be a significant inotropic variable, but the
      quantitative relation between changes in Ca2+ current, action potential duration,
      and developed tension has not been described in a single myocyte. We used the
      action potential voltage-clamp technique on ventricular myocytes loaded with indo
      1 or rhod 2, both Ca2+ indicators, to study the relation between action potential
      duration, ICa-L, and cell shortening (inotropic effect). A rapid change from a
      "short" to a "long" action potential command waveform resulted in an immediate
      decrease in peak ICa-L and a marked slowing of its decline (inactivation).
      Prolongation of the action potential also resulted in slowly developing increases
      in the magnitude of Ca2+ transients (145 +/- 2%) and unloaded cell shortening
      (4.0 +/- 0.4 to 7.6 +/- 0.4 microns). The time-dependent nature of these effects
      suggests that a change in Ca2+ content (loading) of the sarcoplasmic reticulum is
      responsible. Measurement of [Ca2+]i by use of rhod 2 showed that changes in the
      rate of rise of the [Ca2+]i transient (which in rat ventricle is due to the rate
      of Ca2+ release from the sarcoplasmic reticulum) were closely correlated with
      changes in the magnitude and the time course of ICa-L.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7728997
TI  - Spatial distribution of connexin43, the major cardiac gap junction protein,
      visualizes the cellular network for impulse propagation from sinoatrial node to
      atrium.
AB  - Myocytes are electrically coupled by gap junctions, which are composed of low
      resistance intercellular channels. The major cardiac gap junction protein is
      connexin43 (Cx43). The distribution of Cx43 has been studied by
      immunofluorescence to visualize the electrical coupling between atrial tissue and
      sinoatrial node. From modeling studies, this coupling was inferred to be gradual
      in order to shield the sinoatrial node from the atrial hyperpolarizing influence.
      The actual Cx43 labeling pattern did not show the expected gradient but instead a
      rather black and white staining in a striking pattern of strands of cells. We
      used an immunohistochemical marker (anti-alpha-smooth muscle actin [alpha SMA])
      that specifically cross-reacts with guinea pig sinoatrial node cells together
      with Cx43 antibody to stain previously electrophysiologically mapped sinoatrial
      nodes. We found that in the guinea pig sinoatrial node the impulse originates in
      an alpha SMA-positive, virtually Cx43-negative, region (primary pacemaker
      region). The impulse then travels obliquely upward to the crista terminalis
      through a region where layers of alpha SMA-positive cells alternate with layers
      of Cx43-positive SMA-negative cells. The layers of Cx43-positive cells appear to
      become broader and thicker in the direction of the crista terminalis, whereas the
      layers of alpha SMA-positive cells become thinner and narrower. Lateral contacts
      between Cx43- and alpha SMA-positive cells were very sparse and only detected
      where the Cx43-positive strands ended (the region where alpha SMA-positive cells
      fill the whole space between endocardium and epicardium, ie, the putative primary
      pacemaker region). From these results, we conclude that the primary pacemaker is
      shielded from the hyperpolarizing influence of the atrium by a gradient in
      coupling brought about by tissue geometric factors rather than by a gradient of
      gap junction density.

PMID- 7728998
TI  - Oxygen-derived free radical stress activates nonselective cation current in
      guinea pig ventricular myocytes. Role of sulfhydryl groups.
AB  - Oxygen-derived free radicals (O-Rs) cause alterations in cardiac electrical
      activity, including sustained depolarization, which may contribute to arrhythmic
      activity in reperfusion after ischemia. The ionic current(s) and cellular
      mechanism(s) underlying the sustained depolarization are not well defined. We
      used the whole-cell variant of the patch-clamp technique to study sustained
      depolarization in guinea pig ventricular myocytes during the extracellular
      application of O-Rs (generating system: dihydroxyfumaric acid, 3 to 6 mmol/L;
      FeCl3/ADP, 0.05:0.5 mmol/L). Myocytes superfused with O-Rs (pipette EGTA, 0.1
      mmol/L) showed (1) sustained depolarization to between -40 and -10 mV, (2)
      oscillations in membrane potential, and (3) triggered activity. The
      depolarization resulted from an increase in quasi-steady state difference current
      reversing at approximately -18 mV, and the oscillations were due to transient
      inward current. The latter were inhibited with ryanodine (10 mumol/L) or high
      pipette EGTA (5 mmol/L), but the steady state current was unaffected.
      Nonselective cation current (INSC) (recorded with Cs+, Li+, and Mg2+ replacing
      K+, Na+, and Ca2+, respectively; 20 mmol/L tetraethylammonium chloride [TEA] and
      5 mmol/L BAPTA in the pipette solution and 10 mmol/L TEA, 10 mumol/L
      tetrodotoxin, and 10 mumol/L nicardipine in the bath solution) was activated by O
      Rs; the increase in current was unaffected by preventing changes in [Ca2+]i but
      was inhibited with dithiothreitol. Oxidizing agents (diamide and thimerosal) or
      caffeine (pipette EGTA, 0.1 mmol/L) produced a similar increase in membrane
      conductance. INSC activated with O-Rs, oxidizing agents, or caffeine was
      sensitive to SK&F 96365. O-R treatment was without effect when INSC was already
      activated with caffeine. The data suggest that (1) extracellular O-Rs activate a
      Ca(2+)-sensitive INSC in the absence of changes in [Ca2+]i, (2) oxidative
      modification of extracellular sulfhydryl groups may be involved, and (3) this
      mechanism is different from the Ca(2+)-dependent activation of INSC by
      intracellular O-Rs, indicating that O-Rs may alter ion channel activity by
      differential mechanisms, depending on the compartment, extracellular or
      intracellular, in which they are present.

PMID- 7728999
TI  - Na(+)-H+ exchanger isoform 1 phosphorylation in normal Wistar-Kyoto and
      spontaneously hypertensive rats.
AB  - Increased activity of the cellular Na(+)-H+ exchanger (NHE) has been documented
      in various cell types in essential hypertension and in vascular myocytes of the
      spontaneously hypertensive rat (SHR). The mechanism underlying this abnormality
      is unclear. Because the NHE can be activated by phosphorylation, we examined
      phosphorylation of the Na(+)-H+ exchanger isoform 1 (NHE-1) as one possible
      mechanism for its increased turnover number in cultured vascular myocytes of the
      SHR. A polyclonal rabbit antibody against a fusion protein consisting of beta
      galactosidase and the C-terminus of NHE-1 was used to immunoprecipitate 32P
      labeled NHE-1 from cell extracts of SHR and Wistar-Kyoto (WKY) rat vascular
      myocytes in the absence and presence of 10% fetal calf serum. Immunoprecipitates
      were separated by SDS-PAGE, and 32P-labeled NHE-1 was quantified from
      autoradiographs. Similar amounts of NHE-1 protein were detected on Western blots
      of the cultured vascular myocytes from SHR and WKY rats. In quiescent cells, NHE
      1 was significantly more phosphorylated in SHR myocytes than in WKY myocytes
      (2.17 +/- 0.06-fold enhancement [mean +/- SEM]; P < .001, n = 8). The addition of
      fetal calf serum to quiescent cells had no significant effect on the
      phosphorylation of NHE-1 in SHR myocytes. However, NHE-1 phosphorylation fell
      transiently in serum-treated WKY myocytes, with recovery to control levels after
      20 minutes. Measurement of NHE activity using fluorometry confirmed elevated
      activity in the quiescent SHR myocytes compared with WKY myocytes. Fetal calf
      serum led to further enhancement of NHE activity in both cell types. These
      findings suggest that the increased NHE activity in quiescent SHR myocytes may be
      correlated with enhanced NHE-1 phosphorylation and that serum stimulates NHE
      activity in both cell types without a further increase in total NHE-1
      phosphorylation, indicating a role for non-phosphorylation-dependent regulatory
      mechanisms.

PMID- 7729000
TI  - Cardiac muscarinic potassium channel activity is attenuated by inhibitors of G
      beta gamma.
AB  - The cardiac muscarinic potassium channel (IK.ACh) is activated by a G protein
      upon receptor stimulation with acetylcholine. The G protein subunit responsible
      for activation (G alpha versus G beta gamma) has been disputed. We used G beta
      gamma inhibitors derived from the beta-adrenergic kinase 1 (beta ARK1) to assess
      the relative importance of G beta gamma in IK.ACh activation. In rabbit atrial
      myocytes, IK.ACh had a conductance of 49 +/- 6.2 pS. In inside-out patches, the
      mean open time was 1.60 +/- 0.57 ms, mean time constant (tau o) was 1.59 +/- 0.53
      ms, and mean closed time was 3.02 +/- 1.35 ms (n = 38). beta ARK1 is a G beta
      gamma-sensitive enzyme that interacts with G beta gamma through a defined
      sequence near its carboxyl terminus. A 28-amino-acid peptide derived from the
      carboxyl terminus of beta ARK1 (peptide G) increased the closed time to 10.04 ms
      (P < .001) and decreased opening probability (NPo) by 71% (P < .001). Fusion
      proteins containing the entire carboxyl terminus of beta ARK1, glutathione S
      transferase beta ARK1ct and hexahistidine beta ARK1ct, decreased NPo by 67% (P =
      .03) and 48% (P = .009), respectively. They also both significantly increased the
      closed time. None of the inhibitors affected mean open time or channel amplitude.
      A control peptide derived from a neighboring region of beta ARK1 had no
      significant effect on IK.ACh activity. These results provide further evidence for
      the role of G beta gamma in the activation of IK.ACh.

PMID- 7729001
TI  - Pathways of Rb+ influx and their relation to intracellular [Na+] in the perfused
      rat heart. A 87Rb and 23Na NMR study.
AB  - The aims of this study were to characterize the routes of influx of the K+
      congener, Rb+, into cardiac cells in the perfused rat heart and to evaluate their
      links to the intracellular Na+ concentration ([Na+]i) using 87Rb and 23Na nuclear
      magnetic resonance (NMR) spectroscopy. The rate constant for Rb+ equilibration in
      the extracellular space was 8.5 times higher than that for the intracellular
      space. The sensitivity of the rate of Rb+ accumulation in the intracellular space
      of the perfused rat heart to the inhibitors of the K+ and Na+ transport systems
      has been analyzed. The Rb+ influx rates were measured in both beating and
      arrested hearts: both procaine (5 mmol/L) and lidocaine (1 mmol/L) halved the Rb+
      influx rate. In procaine-arrested hearts, the Na+,K(+)-ATPase inhibitor ouabain
      (0.6 mmol/L) decreased Rb+ influx by 76 +/- 24% relative to that observed in
      untreated but arrested hearts. Rb+ uptake was insensitive to the K+ channel
      blocker 4-aminopyridine (1 mmol/L). The inhibitor of Na+/K+/2 Cl- cotransport
      bumetanide (30 mumol/L) decreased Rb+ uptake only slightly (by 9 +/- 8%). Rb+
      uptake was dependent on [Na+]i: it increased by 58 +/- 34% when [Na+]i was
      increased with the Na+ ionophore monensin (1 mumol/L) and decreased by 48 +/- 9%
      when [Na+]i was decreased by the Na+ channel blockers procaine and lidocaine.
      Dimethylamiloride (15 to 20 mumol/L), an inhibitor of the Na+/H+ exchanger,
      slightly reduced [Na+]i and Rb+ entry into the cardiomyocytes (by 15 +/- 5%). 31P
      NMR spectroscopy was used to monitor the energetic state and intracellular pH
      (pHi) in a parallel series of hearts. Treatment of the hearts with lidocaine, 4
      aminopyridine, dimethylamiloride, or bumetanide for 15 to 20 minutes at the same
      concentrations as used for the Rb+ and Na+ experiments did not markedly affect
      the levels of the phosphate metabolites or pHi. These data show that under normal
      physiological conditions, Rb+ influx occurs mainly through Na+,K(+)-ATPase; the
      contribution of the Na+/K+/2 Cl- cotransporter and K+ channels to Rb+ influx is
      small. The correlation between Rb+ influx and [Na+bdi during infusion of drugs
      that affect [Na+]i indicates that, in rat hearts at 37 degrees C, Rb+ influx can
      serve as a measure of Na+ influx. We estimate that, at normothermia, at least 50%
      of the Na+ entry into beating cardiac cells is provided by the Na+ channels, with
      only minor contributions (< 15%) from the Na+/K+/2 Cl- cotransporter and the
      Na+/H+ exchanger.

PMID- 7729002
TI  - Decreased adenylate cyclase activity and expression of Gs alpha in human
      myocardium after orthotopic cardiac transplantation.
AB  - We studied several aspects of guanine nucleotide-stimulated adenylate cyclase
      function in patients after orthotopic cardiac transplantation. In 28 patients,
      adenylate cyclase activity was measured in endomyocardial biopsy samples obtained
      just before and at monthly intervals after cardiac transplantation. In biopsies
      obtained > or = 6 months after transplantation, basal adenylate cyclase activity
      was decreased by 67% (n = 12; P < .05), GTP gamma S-stimulated adenylate cyclase
      activity was decreased by 78% (n = 12; P < .05), Mn+2+forskolin-stimulated
      adenylate cyclase activity was decreased by 80% (n = 8; P < .05), and Mn+2
      stimulated adenylate cyclase activity (a measure of activity of the catalytic
      subunit of adenylate cyclase) was decreased by 83% (n = 8, P < .05). Western blot
      analysis demonstrated that 6 months after cardiac transplantation, the level of
      Gs alpha protein was decreased by 61 +/- 12% (n = 8; P < .001). There was no
      change in the level of Gi alpha as assessed by pertussis toxin-catalyzed ADP
      ribosylation (n = 4; P = NS). With the use of the quantitative polymerase chain
      reaction, a 50 +/- 10% (n = 6; P < .001) reduction in the steady-state level of
      Gs alpha mRNA was observed. There was no change in the level of mRNA for Gi-3
      alpha. Thus, after orthotopic cardiac transplantation in humans, guanine
      nucleotide-stimulated adenylate cyclase activity is decreased in parallel with
      decreased levels of Gs alpha protein and mRNA.

PMID- 7729003
TI  - Impaired function of inhibitory G proteins during acute myocardial ischemia of
      canine hearts and its reversal during reperfusion and a second period of
      ischemia. Possible implications for the protective mechanism of ischemic
      preconditioning.
AB  - A brief antecedent period of myocardial ischemia and reperfusion can delay
      cellular injury during a subsequent ischemic condition. Recent observations
      suggest that this protective mechanism depends on the continued activation of
      adenosine A1 receptors and Gi proteins. During acute myocardial ischemia,
      sufficient amounts of adenosine for maximal activation of adenosine A1 receptors
      are released, independent of a preconditioning ischemia. Hence, the protective
      mechanism of ischemic preconditioning may not exclusively be explained by
      activation of adenosine A1 receptors. As a working hypothesis, an increased
      responsiveness of Gi proteins toward receptor-mediated activation, leading to an
      increased response of Gi-regulated effectors, was tested in this study. In 47
      anesthetized dogs, ischemia was induced by proximal ligation of the left anterior
      descending coronary artery. Animals underwent either a single period of 5 minutes
      of ischemia (n = 9), a single period of 15 minutes of ischemia (n = 10), 5
      minutes of ischemia followed by 15 minutes of reperfusion (n = 8), 15 minutes of
      ischemia followed by 60 minutes of reperfusion (n = 5), or 5 minutes of ischemia
      followed by 15 minutes of reperfusion and a second period of 5 minutes of
      ischemia (n = 15). Sarcolemmal membranes were prepared from the central ischemic
      area and from the posterior left ventricular wall, which served as the control.
      During ischemia, carbochol-stimulated GTPase decreased by 38% (control, 33.5 +/-
      17.7; ischemia, 24.2 +/- 15 pmol.min-1.mg protein-1; n = 9; P < .001). The
      decrease in carbachol-stimulated GTPase activity was associated with a 45%
      decrease in carbachol-mediated inhibition of adenylyl cyclase (control, 28.9 +/-
      2.4% maximal inhibition; ischemia, 15.1 +/- 2.6% maximal inhibition; n = 5; P <
      .001). Prolongation of the ischemic period to 15 minutes did not lead to a
      further reduction of the Gi-mediated signal transduction. The binding properties
      of muscarinic receptors were not affected by ischemia. Furthermore, as
      demonstrated by carbachol-stimulated binding of [gamma-35S]GTP to sarcolemmal
      membranes, high- and low-affinity binding sites for the muscarinic antagonist
      carbachol, the EC50 for carbachol-stimulated GTPase activity and the substrate
      dependency of the high-affinity GTPase, the interaction between muscarinic
      receptors and inhibitory G proteins, and GTP binding to G proteins were not
      altered (n = 14). Immunoblotting with alpha 1- and alpha 2-specific antibodies
      did not indicate a loss of Gi proteins during ischemia that could explain the
      reduced GTPase activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7729004
TI  - Intracardiac blood flow patterns related to the yolk sac circulation of the chick
      embryo.
AB  - Intracardiac flow patterns during heart development were studied by injection of
      india ink into the yolk sac circulation of chick embryos at Hamburger-Hamilton
      stages 10 to 17. We injected india ink into a small venule or capillary,
      carefully preventing application of overpressure to the vascular system, and
      recorded the intracardiac route by video. From stage 12 onward, blood flow was
      laminar, and separate intracardiac currents were visualized. The yolk sac was
      divided into a left and a right half. Blood coursed through each half in
      concentric loops, ranging from the marginal sinus to the sinus venosus. This
      parallel array persisted within the heart. Bilateral to the embryo, two lateral
      regions arose that extended wedge-like within each half, resulting in six equally
      sized yolk sac regions at stage 16. The process of heart looping was not
      accompanied by a change in flow pattern. However, developmental changes of the
      yolk sac circulation were reflected in alteration of the intracardiac flow
      pattern. From stage 16 onward, the intracardiac flow pattern was no longer
      determined by the left- or right-hand side of the yolk sac but by bilateral
      anterior, lateral, and posterior regions of the yolk sac. Blood from the lateral
      regions of the yolk sac was preferentially distributed to the head. The results
      show that in preseptation stages a relatively stable flow pattern is present. We
      suggest that alterations in blood flow could influence the process of normal
      heart development.

PMID- 7729005
TI  - Endothelin-mediated positive inotropic effect induced by reactive oxygen species
      in isolated cardiac muscle.
AB  - Cardiac endothelium, both coronary and endocardial, produces a number of
      inotropic molecules. Changes in cardiac endothelial function by substances in the
      superfusing blood may thus participate in the control of muscle-pump performance
      of the heart. Reactive oxygen species (ROS) have been implicated in normal and
      pathological vascular physiology by influencing vascular endothelial function.
      Therefore, we examined the influence of ROS on endocardial endothelial modulation
      of myocardial performance. Right ventricular cat papillary muscles were briefly
      (15 s) exposed to electrolysis-generated ROS. Peak total isometric twitch tension
      and peak rate of tension development increased by 7.8 +/- 0.7% (P < .05) and 9.7
      +/- 1.5% (P < .05), respectively (n = 12). Isometric twitch duration was slightly
      increased (time from stimulus to half isometric relaxation, +2.7 +/- 0.6%; P <
      .05). ROS scavengers such as ascorbic acid (n = 6), superoxide dismutase and
      catalase (n = 8), or catalase alone (n = 6), but not superoxide dismutase alone
      (n = 6), blocked the inotropic effect. Interestingly, the positive inotropic
      effect was completely blocked by selectively damaging endocardial endothelium
      (Triton X-100, 0.5%, 1-s immersion, n = 7) before ROS generation and by
      preincubating the muscles with the endothelin-A receptor antagonist BQ 123 (n =
      11). Preincubation with NG-nitro-L-arginine methyl ester and indomethacin (n = 5)
      or with atenolol (n = 6) did not influence the inotropic effect.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7729006
TI  - Interaction between conducted vasodilation and sympathetic nerve activation in
      arterioles of hamster striated muscle.
AB  - We tested the hypothesis that sympathetic nerve activity can influence the
      conduction of vasodilation along the arteriolar wall. Arterioles in the
      superfused cremaster muscle of anesthetized male hamsters (n = 21, 109 +/- 4 g)
      were studied. Microelectrodes were positioned adjacent to the distal end of
      primary arterioles to stimulate sympathetic nerves throughout arteriolar networks
      (perivascular nerve stimulation [PNS]). Microiontophoresis micropipettes (tip
      outer diameter, 1 to 2 microns) filled with acetylcholine (ACh, 1 mol/L) were
      positioned adjacent to the wall of second-order (2A) or third-order (3A)
      arterioles approximately 1 mm distal to their origin to induce local and
      conducted vasodilation; diameter responses were recorded at the micropipette tip
      and at vessel origins, respectively. For 2A and 3A arterioles (resting diameters,
      15 to 54 and 9 to 30 microns, respectively), vasoconstriction with PNS was
      frequency dependent (0.5 to 32 Hz); this was attenuated by 65% (P < .05) with
      alpha-adrenoceptor blockade (phentolamine, 1 mumol/L). Conducted vasodilation was
      attenuated by > 40% during 16-Hz PNS (P < .05); this effect was reversed by
      phentolamine. In a reciprocal fashion, conducted vasodilation diminished PNS
      induced vasoconstriction by approximately 50% (P < .05). Elevating oxygen (from
      0% to 10%) in the superfusion solution induced vasoconstriction similar to that
      with 16-Hz PNS yet had no effect on conduction. Neural blockade with tetrodotoxin
      (1 mumol/L) eliminated PNS-induced vasoconstriction and enhanced (P < .05)
      conducted vasodilation. These findings indicate that perivascular nerves in
      striated muscle can influence cell-to-cell communication along the arteriolar
      wall both at rest and during enhanced sympathetic activity.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7729007
TI  - Regression of left ventricular hypertrophy prevents ischemia-induced lethal
      arrhythmias. Beneficial effect of angiotensin II blockade.
AB  - To evaluate the preventive effect of regression of left ventricular hypertrophy
      (LVH) on sudden cardiac death (SCD), the incidence of ventricular tachycardia or
      ventricular fibrillation (VT/Vf) after left coronary artery occlusion in
      Langendorff preparations was studied in the following five groups: (1)
      spontaneously hypertensive rats (SHR) without treatment (SHR-N), (2) SHR treated
      with captopril (SHR-C), (3) SHR treated with the angiotensin II receptor
      antagonist TCV-116 (SHR-A), (4) SHR treated with hydralazine (SHR-H), and (5)
      Wistar-Kyoto (WKY) rats. Although blood pressure was equally lowered in all
      treated groups, SHR-C and SHR-A but not SHR-H showed regression of LVH. The
      incidence of VT/Vf was 5% in WKY rats, 63% in SHR-N (P < .005 versus WKY rats),
      0% in SHR-C, 10% in SHR-A, and 45% in SHR-H (P < .05 versus WKY rats). Further
      evaluation of the effect of TCV-116 revealed that SHR treated with a low dose of
      TCV-116 (1 mg/kg per day) showed a decrease in left ventricular mass with only a
      little decrease in blood pressure and that the incidence of VT/Vf was reduced in
      association with the degree of regression of LVH. Electrophysiological study
      using microelectrode techniques revealed that in the LVH groups (SHR-N and SHR
      H), the action potential duration (APD) of the left ventricular papillary muscle
      was more prolonged than in WKY rats, whereas APD shortened to a greater extent
      during superfusion with a hypoxia/no-glucose solution. APD showed no difference
      in the regression groups (SHR-C and SHR-A) compared with the WKY group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7729008
TI  - Enhanced preservation of orthotopically transplanted rat lungs by nitroglycerin
      but not hydralazine. Requirement for graft vascular homeostasis beyond harvest
      vasodilation.
AB  - Nitric oxide (NO) produced within the lungs maintains pulmonary vascular
      homeostatic properties, modulating leukocyte traffic, platelet aggregation, and
      vasomotor tone. Because reactive oxygen intermediates generated during
      reperfusion react rapidly with available NO, we hypothesized that the NO donor
      nitroglycerin (NTG) would enhance lung preservation for transplantation by
      improving graft blood flow and reducing graft neutrophil and platelet
      sequestration. By use of an orthotopic rat left lung transplant model, with
      ligation of the native right pulmonary artery to ensure that recipient survival
      and physiological measurements depend entirely on the transplanted lung,
      transplants were performed in 70 male Lewis rats after 6-hour 4 degrees C
      preservation in Euro-Collins solution (EC) alone or EC with supplemental NTG.
      Compared with EC alone, supplemental NTG significantly increased pulmonary
      arterial flow (2.2 +/- 1.4 to 21.4 +/- 2.9 mL/min, P < .01), decreased pulmonary
      vascular resistance (7.4 +/- 2.0 to 1.4 +/- 0.1 x 10(3) Woods units, P < .05),
      improved arterial oxygenation (163 +/- 57 to 501 +/- 31 mm Hg, P < .01), and
      enhanced recipient survival (17% to 100%, P < .001). These beneficial effects of
      NTG were dose dependent over a range of 0.001 to 0.1 mg/mL. Although NTG caused
      significant pulmonary vasodilation during the harvest/flushing period, the direct
      acting vasodilator hydralazine caused greater vasodilation than did NTG but was
      associated with poor graft function, elevated pulmonary vascular resistance, and
      poor recipient survival. To explore nonvasodilator protective mechanisms of NTG,
      graft neutrophil and platelet sequestration were studied; supplemental NTG
      significantly reduced both neutrophil and platelet accumulation compared with
      either hydralazine or EC alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729009
TI  - Echocardiographic assessment of left ventricular mass and systolic function in
      mice.
AB  - The increasing use of transgenic mouse models for investigating the mechanisms of
      cardiac growth and function has made it important to develop noninvasive methods
      for assessing murine cardiac anatomy, size, and function. At present, murine
      cardiac mass can be determined only at necropsy. Left ventricular (LV) function
      can be assessed by use of various catheterization techniques, but these
      approaches are usually terminal procedures and provide no information about
      chamber anatomy and dimensions. Although transthoracic echocardiography has been
      used to study the LVs of rats and larger animals, the considerably smaller LV
      masses and somewhat faster heart rates of mice pose significant challenges to
      obtaining good-quality echocardiograms. In this study we tested the hypothesis
      that transthoracic echocardiography can image the murine LV as well as provide
      assessments of LV mass and function. Our results in a series of 33 mice,
      including normal, transgenic, and aortic-banded subgroups, demonstrate the
      capability of transthoracic two-dimensionally directed M-mode echocardiography in
      mice to (1) obtain good-quality images, (2) produce estimates of LV mass having
      good correlations with directly determined LV mass in normal mice, (3) detect LV
      hypertrophy noninvasively in different experimental models, and (4) identify
      impaired LV systolic function. Thus, echocardiography appears to be a promising
      approach for noninvasively assessing LV mass and function in mice.

PMID- 7729010
TI  - Biphasic restitution of action potential duration and complex dynamics in
      ventricular myocardium.
AB  - The purpose of this study was to determine whether biphasic restitution of action
      potential duration (APD) in ventricular muscle permits the development of complex
      dynamic behavior. Such behavior is expected because of the steep ascending slope
      of restitution and the presence of a maximum. Action potentials recorded from
      strips of epicardial muscle in which biphasic APD restitution occurred
      demonstrated a characteristic pattern of phase locking during progressive
      shortening of the pacing cycle length. 1:1 locking was replaced by irregular
      dynamics, which in turn was replaced by higher order periodic behavior (eg, 8:8
      locking), then by 2:2 locking, and finally by 2:1 locking. Similar patterns of
      dynamic behavior were produced in a computer model by using a piecewise linear
      approximation of biphasic APD restitution. Features of APD restitution that were
      critical determinants of irregular dynamics included the slopes of the ascending
      and the nonmonotonic regions. These results suggest that rate-related alterations
      of APD and refractoriness may be affected significantly by small
      nonmonotonicities in APD restitution.

PMID- 7729011
TI  - Simultaneous measurements of Ca2+ and nitric oxide in bradykinin-stimulated
      vascular endothelial cells.
AB  - The production of endothelium-derived relaxing factor (EDRF), known to be nitric
      oxide (NO), is triggered by a rise in the cytoplasmic calcium concentration
      ([Ca2+]i) subsequent to receptor binding of vasoactive agonists. In vascular
      endothelial cells, NO is synthesized from L-arginine by the Ca2+/calmodulin
      dependent NO synthase. In this study, we report the first simultaneous
      measurements of [Ca2+]i and [NO] at the level of single endothelial cells. In
      cultured bovine aortic endothelial cells, extracellular application of bradykinin
      (BK, 10 to 20 mumol/L) caused transient (sometimes oscillatory) increase in
      [Ca2+]i, which was measured with the fluorescent Ca2+ indicator fura 2 and
      fluorescence imaging microscopy. BK caused an increase in [Ca2+]i, primarily
      through release from intracellular stores. Under identical experimental
      conditions, BK caused a transient increase in [NO], which was measured by
      application of a porphyrinic NO microsensor. [NO] peaked at approximately 0.5
      mumol/L. Simultaneous measurements of [Ca2+]i and [NO] in BK-stimulated
      endothelial cells revealed that a transient increase in [Ca2+]i was rapidly
      followed by an increase in [NO] that outlasted the [Ca2+]i transient.

PMID- 7729012
TI  - Angiographic and clinical progression in unstable angina. From clinical
      observations to clinical trials.

PMID- 7729013
TI  - Metabolic complexities in cardiac imaging.

PMID- 7729014
TI  - A de novo mutation in alpha-tropomyosin that causes hypertrophic cardiomyopathy.
AB  - BACKGROUND: Two missense mutations in the gene for alpha-tropomyosin have been
      described that segregate with hypertrophic cardiomyopathy in single families. To
      confirm that these mutations are the cause of the disease, we have investigated
      the origins of one of these mutations, Asp175Asn, in a third and unrelated
      family. METHODS AND RESULTS: The presence or absence of an alpha-tropomyosin
      mutation and the haplotypes of the flanking chromosomal regions were determined
      for members of a family with hypertrophic cardiomyopathy. Haplotypes were
      constructed by use of an intragenic polymorphism and 10 flanking polymorphisms
      spanning a region of 35 centimorgans. The Asp175Asn missense mutation was present
      in the proband and his two affected offspring but not in any of the proband's
      three siblings. Although both parents were deceased, the haplotypes of the four
      parental chromosomes could be reconstructed. One parental chromosome was
      transmitted to two offspring: one bearing the Asp175Asn mutation (the affected
      proband) and one clinically unaffected sibling who lacked the alpha-tropomyosin
      mutation. Thus, the Asp175Asn mutation must have arisen de novo. CONCLUSIONS: De
      novo mutations in the alpha-tropomyosin gene can result in hypertrophic
      cardiomyopathy that may appear to be sporadic but in subsequent generations gives
      rise to familial disease. Individuals with sporadic hypertrophic cardiomyopathy
      should be advised of the risk of transmission to offspring. In addition, these
      findings provide the strongest genetic evidence that mutations in the alpha
      tropomyosin gene are directly responsible for hypertrophic cardiomyopathy.

PMID- 7729015
TI  - Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory
      carbon monoxide.
AB  - BACKGROUND: Carbon monoxide (CO), like nitric oxide (NO), stimulates soluble
      guanylyl cyclase and thereby raises intracellular levels of cGMP. We examined the
      endogenous capacity of vascular smooth muscle cells (SMCs) to produce CO from
      heme through the activity of heme oxygenases. METHODS AND RESULTS: Cultured SMCs
      from rat aorta (RASMCs) expressed immunoreactive inducible heme oxygenase-1 (HO
      1) and constitutive HO-2. Treatment of RASMCs with hemin and sodium arsenite,
      which are inducers of HO-1, stimulated RASMC cGMP without stimulating nitrite
      release or inducible NO synthase expression, and the induced elevations of cGMP
      were not inhibited by the NO synthase inhibitor NG-methyl-L-arginine. Induced CO
      from RASMCs likewise caused elevation of cGMP levels in platelets coincubated
      with the vascular cells. Zinc protoporphyrin IX, an inhibitor of HO, reversed the
      inducible increases in platelet cGMP. CONCLUSIONS: These results indicate that
      vascular SMCs have both constitutive and inducible HO activity, and they respond
      to specific stimuli to generate guanylyl cyclase-stimulatory CO in the same SMCs
      and in coincubated platelets.

PMID- 7729016
TI  - Reverse remodeling from cardiomyoplasty in human heart failure. External
      constraint versus active assist.
AB  - BACKGROUND: Cardiomyoplasty (CM) is a novel surgical therapy for dilated
      cardiomyopathy. In this procedure, the latissimus dorsi muscle is wrapped around
      the heart and chronically paced synchronously with ventricular systole. While
      studies have found symptomatic improvement from this therapy, the mechanisms by
      which CM confers benefit remain uncertain. This study sought to better define
      these mechanisms by means of serial pressure-volume relation analysis. METHODS
      AND RESULTS: Serial pressure-volume studies were performed by the conductance
      catheter method in three patients (total to date) with dilated cardiomyopathy
      (New York Heart Association class III) who underwent CM. Data were measured at
      baseline (before surgery) and at 6 and 12 months after CM. Chronic left
      ventricular (LV) systolic and diastolic changes induced by CM were evaluated with
      the stimulator in its stable pacing mode (every other beat) and after temporarily
      suspending pacing. CM-stimulated beats were compared with pacing-off beats to
      evaluate active systolic assist effects of CM. In each patient, CM resulted in a
      chronic lowering of cardiac end-diastolic volume and an increased ejection
      fraction. Most notably, the end-systolic pressure-volume relation shifted
      leftward, consistent with reversal of chronic chamber remodeling. In contrast,
      the diastolic pressure-volume relation was minimally altered, and the loops
      shifted down along the same baseline relation. These marked chronic changes in LV
      function measurable with CM stimulation off contrasted to only minor acute
      effects observed when the muscle wrap was activated. This suggests that the
      benefit of CM derived less from active systolic assist than from remodeling,
      perhaps because of an external elastic constraint. CONCLUSIONS: These data, while
      limited to a small number of patients, suggest that CM can reverse remodeling of
      the dilated failing heart. While systolic squeezing assist effects of CM may play
      a role in some patients, our study found that this was not required to achieve
      substantial benefits from the procedure. We speculate that CM may act more
      passively, like an elastic girdle around the heart, to help reverse chamber
      remodeling.

PMID- 7729017
TI  - Angiographic stenosis progression and coronary events in patients with
      'stabilized' unstable angina.
AB  - BACKGROUND: Recent studies suggest that angiographically complex coronary
      stenoses are associated with an adverse short-term outcome. It is not known,
      however, if this applies to unstable angina patients who stabilize on medical
      therapy. METHODS AND RESULTS: We prospectively studied 85 consecutive patients
      with unstable angina who stabilized on medical therapy but were found to require
      angioplasty for treatment of obstructive coronary disease. Angiography was
      carried out at admission, and patients were restudied 8 +/- 4 months (mean +/-
      SD) after the first angiogram. Ischemia-related stenoses were identified and
      classified as "complex" (irregular borders, overhanging edges, or thrombus) or
      "smooth" (absence of complex features). Stenosis progression (> or = 20% diameter
      reduction or new total occlusion) was assessed by automated edge detection. At
      initial angiography, there were 198 stenoses (> or = 50%, 102), of which 85 (54
      complex and 31 smooth) were ischemia related. At restudy, 21 ischemia-related
      stenoses and 8 non-ischemia-related stenoses progressed (25% versus 7%, P =
      .001). Seventeen of the 21 ischemia-related stenoses that progressed developed
      into total occlusion compared with 3 of the 8 non-ischemia-related stenoses (P =
      .02). Changes in average stenosis severity and in absolute stenosis diameter were
      significantly larger in ischemia-related stenoses than in non-ischemia-related
      stenoses (P = .03). Eighteen (34%) complex stenoses progressed, compared with 3
      (10%) smooth lesions (P = .02). During follow-up, 1 patient died (myocardial
      infarction) and 25 patients had nonfatal coronary events that were associated
      with progression of ischemia-related stenoses in 14 (56%). CONCLUSIONS: In
      unstable angina patients who stabilize medically, subsequent short-term stenosis
      progression and coronary events are common. The unstable coronary lesion
      (particularly complex stenoses) is often not stabilized and will continue to
      progress over the ensuing months.

PMID- 7729018
TI  - Comparison of surgical and medical group survival in patients with left main
      coronary artery disease. Long-term CASS experience.
AB  - BACKGROUND: Observational and randomized studies designed to compare surgical and
      medical therapies in patients with left main coronary artery disease (LMCD) have
      shown that coronary artery bypass graft (CABG) surgery prolongs life in most
      patients with LMCD. The present report of 1484 patients with LMCD in the Coronary
      Artery Surgery Study (CASS) Registry extends the originally published 5-year
      surgical and medical group survival analysis to more than 16 years of follow-up
      and permits analysis of LMCD patient subgroups. METHODS AND RESULTS: The CASS
      Registry contains 1484 patients with > or = 50% left main coronary artery
      stenosis initially treated with either surgical or nonsurgical therapy. The 15
      year cumulative survival estimates were 37% for the 1153 patients in the surgical
      group compared with 27% for the 331 patients in the medical group. Median
      survival in the surgical group was 13.3 years (12.8 to 13.8 years, 95% confidence
      limits) compared with only 6.6 years (5.4 to 7.9 years) in the medical group
      (difference, 6.7 years; P < .0001). Median survival was also significantly longer
      in the surgical group stratified by age, sex, anginal class, left ventricular
      (LV) function, coronary anatomy, and the extent of LMCD. However, CABG surgery
      did not significantly prolong median survival in patient subgroups with (1) left
      main coronary stenosis of 50% to 59%; (2) normal LV systolic function; (3) normal
      or mildly abnormal LV systolic function and a right coronary artery stenosis > or
      = 70%; and (4) a nonstenotic (< or = 70%) right coronary artery. The 15-year
      cumulative survival for patients with normal LV systolic function in the surgical
      and medical groups was 42% and 51%, respectively. Median survival was 14.7 years
      in the surgical group and > 15 years in the medical group (P = NS). In patients
      with normal LV systolic function and a right coronary artery stenosis > or = 70%,
      the 15-year cumulative survival rates were also similar in the surgical and
      medical groups (40% and 48%, respectively). Median survival was 14.3 years in the
      surgical group and 14.2 years in the medical group (P = NS). The 15-year
      cumulative survival estimates for all subgroups were affected by convergence of
      the surgical and medical survival group curves owing to a disproportionate
      increase in the late surgical group mortality. Overall, 25% of patients in the
      medical group ultimately underwent CABG surgery. If all medical group patients
      had survived long enough, about 47% would be estimated to have had surgery by 15
      years. CONCLUSIONS: This report, which extends follow-up of more than 16 years in
      CASS Registry patients with LMCD, shows that CABG surgery prolongs life in most
      clinical and angiographic subgroups. However, median survival was not prolonged
      by CABG surgery in patients with normal LV systolic function, even if a
      significant right coronary artery stenosis (> or = 70%) also was present. These
      results extend our understanding of the natural history of LMCD and permit a more
      accurate estimate of long-term surgical and medical group survival.

PMID- 7729019
TI  - Comparison of surgical and medical group survival in patients with left main
      equivalent coronary artery disease. Long-term CASS experience.
AB  - BACKGROUND: Combined severe proximal left anterior descending and proximal left
      circumflex coronary artery disease, or left main equivalent (LMEQ) disease,
      defines a prognostic high-risk angiographic subset of patients with chronic
      ischemic heart disease. While numerous observational and randomized clinical
      trials showed prolonged survival in surgically compared with medically treated
      patients with left main coronary artery disease, relatively few observational
      studies compared surgical and medical therapies in patients with LMEQ disease.
      The present report of 912 patients with LMEQ disease in the Coronary Artery
      Surgery Study (CASS) Registry extends the originally published 5-year surgical
      and medical group survival analysis to more than 16 years of follow-up and
      permits analysis of LMEQ patient subgroups. METHODS AND RESULTS: The CASS
      Registry contains 912 patients with LMEQ disease, defined as combined stenoses of
      > or = 70% in the proximal left anterior descending coronary artery before the
      first septal perforator and proximal circumflex coronary artery before the first
      obtuse marginal branch, initially treated with either surgical or nonsurgical
      therapy. The 15-year cumulative survival estimates were 44% for the 630 patients
      in the surgical group and 31% for the 282 patients in the medical group. Median
      survival in the surgical group was 13.1 years (12.7 to 14.1 years, 95% confidence
      limits) compared with only 6.2 years (4.8 to 7.9 years) in the medical group
      (difference, 6.9 years; P < .0001). Median survival was also significantly longer
      in the surgical group stratified by age, sex, anginal class, left ventricular
      (LV) function, and coronary anatomy. However, coronary artery bypass graft (CABG)
      surgery did not significantly prolong median survival in patient subgroups with
      (1) normal LV systolic function, even if a significant right coronary artery
      stenosis (> or = 70%) also was present, and (2) mildly abnormal (LV score, 6 to
      10) LV systolic function. The 15-year cumulative survival in patients with normal
      LV systolic function in the surgical and medical groups was 63% and 54%,
      respectively. Median survival was > 15 years in both the surgical and medical
      groups (P = NS). In patients with normal LV systolic function and right coronary
      artery stenosis > or = 70%, the 15-year cumulative survival was also similar in
      the surgical and medical groups (63% and 53%, respectively). Median survival was
      > 15 years in both the surgical and medical groups (P = NS). The 15-year
      cumulative survival estimates in all subgroups were affected by convergence of
      the surgical and medical group survival curves caused by a disproportionate
      increase in late surgical group mortality. Overall, 26% of patients in the
      medical group ultimately underwent CABG surgery. If all medical group patients
      had survived long enough, about 65% would be estimated to have had surgery by 15
      years. When the CASS Registry patients with LMEQ disease who participated in the
      randomized trial or who were randomizable were analyzed, CABG surgery did not
      prolong the 15-year cumulative survival estimates compared with nonsurgical
      therapy for randomized (71% versus 67%, respectively) and for randomizable
      patients (62% versus 92%, respectively) with an LV ejection fraction > or = 50%.
      CONCLUSIONS: This report, which extends follow-up of more than 16 years in CASS
      Registry patients with LMEQ disease, shows that CABG surgery prolongs life in
      most clinical and angiographic subgroups. However, median survival was not
      prolonged by CABG surgery in patients with normal LV systolic function, even if a
      significant right coronary artery stenosis (> or = 70%) also was present or in
      patients with an LV ejection fraction > or = 50% who participated in the CASS
      randomized trial or who were randomizable.

PMID- 7729020
TI  - Impaired endothelium-dependent vasodilation of coronary resistance vessels is
      associated with exercise-induced myocardial ischemia.
AB  - BACKGROUND: The release of endothelium-derived relaxing factors has been shown
      experimentally to be of pivotal importance for the maintenance of coronary blood
      flow during increased demand. In humans with coronary atherosclerosis,
      endothelial vasodilator dysfunction is not confined only to epicardial
      conductance vessels but may also extend into the coronary microcirculation. We
      therefore tested the hypothesis that endothelial vasodilator dysfunction of the
      coronary resistance vasculature is associated with myocardial ischemia during
      exercise in patients without hemodynamically significant epicardial artery
      stenoses. METHODS AND RESULTS: Coronary vasodilator function was assessed by
      subselective infusion of the endothelium-dependent dilator acetylcholine (0.036
      to 3.6 micrograms/mL) and the endothelium-independent dilator papaverine (7 mg).
      Coronary blood flow responses were evaluated by intracoronary Doppler flow
      velocity recordings and quantitative angiography. Exercise-induced myocardial
      perfusion was determined by 201Tl single photon emission computed tomographic
      imaging. Thirteen patients had exercise-induced myocardial perfusion defects
      suggestive of myocardial ischemia, whereas 14 patients had normal thallium
      imaging during exercise. In patients with exercise-induced thallium perfusion
      defects, coronary blood flow responses to acetylcholine were significantly (P <
      .005) blunted compared with patients with normal thallium imaging during
      exercise. In contrast, coronary blood flow reserve to the endothelium-independent
      smooth muscle relaxant papaverine was similar in the two groups. Patients with
      exercise-induced thallium perfusion defects exhibited a significantly (P < .005)
      reduced (23.9 +/- 9.0% [mean +/- SD]) endothelium-mediated coronary vasodilator
      capacity compared with patients with normal thallium testing (56.2 +/- 27.8%).
      Epicardial artery vasoreactivity to acetylcholine did not differ between the two
      groups. CONCLUSIONS: Impaired endothelium-dependent vasodilation of the coronary
      microcirculation is associated with exercise-induced myocardial ischemia in
      patients without hemodynamically significant epicardial artery lesions.
      Endothelial vasodilator dysfunction extending into the coronary microcirculation
      may thus contribute to the ischemic manifestations of coronary artery disease
      during times of increased myocardial demand.

PMID- 7729021
TI  - Normalization of diastolic dysfunction in aortic stenosis late after valve
      replacement.
AB  - BACKGROUND: The remodeling of the left ventricle in patients with aortic stenosis
      after aortic valve replacement (AVR) is a complex process involving structural
      and functional changes. METHODS AND RESULTS: Twenty-two patients were included in
      the present analysis. Twelve patients with severe aortic stenosis were studied
      before surgery, early (22 +/- 8 months) and late (81 +/- 22 months) after AVR
      using left ventricular biplane angiograms, high-fidelity pressure measurements,
      and endomyocardial biopsies. Ten healthy subjects were used as controls. Left
      ventricular systolic function was assessed from biplane ejection fraction; and
      diastolic function from the time constant of relaxation, the peak filling rate,
      and the myocardial stiffness constant. Left ventricular structure was evaluated
      from interstitial fibrosis, fibrous content, and muscle fiber diameter. Left
      ventricular muscle mass was significantly increased before surgery in patients
      with aortic stenosis and remained increased early after surgery, although there
      was a 35% decrease. Late after AVR, muscle mass decreased significantly but
      remained slightly (P = NS) elevated. Left ventricular ejection fraction increased
      slightly after AVR. Left ventricular relaxation was significantly prolonged
      before surgery and returned toward normal early and late after AVR. Peak filling
      rates remained unchanged before and after surgery. Myocardial stiffness constant
      was increased before surgery in patients with aortic stenosis compared with
      controls and increased even further early after AVR but was normalized late after
      surgery. Muscle fiber diameter was elevated in patients with aortic stenosis
      before and after surgery compared with controls; however, it decreased
      significantly early and late after AVR with respect to preoperative data but
      remained hypertrophied even late after surgery. Interstitial fibrosis and fibrous
      contents were larger before surgery than in control subjects and increased even
      more early but decreased significantly late after AVR. CONCLUSIONS: Diastolic
      stiffness increases in aortic stenosis early after AVR parallel to the increase
      in interstitial fibrosis, whereas relaxation rate decreases with a reduction in
      left ventricular muscle mass. Late after AVR, both diastolic stiffness and
      relaxation are normalized due to the regression of both muscular and nonmuscular
      tissue. Thus, reversal of diastolic dysfunction in aortic stenosis takes years
      and is accompanied by a slow regression of interstitial fibrosis.

PMID- 7729022
TI  - Regional left ventricular systolic function in relation to the cavity geometry in
      patients with chronic right ventricular pressure overload. A three-dimensional
      tagged magnetic resonance imaging study.
AB  - BACKGROUND: Distortion of the left ventricular (LV) cavity in patients with right
      ventricular pressure overload (RVPO) is well known. However, no direct
      measurements of regional myocardial function in terms of myocardial shortening
      and wall thickening are available; therefore, exactly how RVPO disturbs LV
      regional performance remains unclear. By using three-dimensional (3D) tagged
      magnetic resonance imaging, we were able to measure regional systolic function
      directly. Our objective was to study the relation between the distortion of the
      LV circular shape and regional LV function. METHODS AND RESULTS: In nine patients
      with RVPO and six healthy volunteers, four parallel short-axis images (with 12
      radial tags) and two mutually orthogonal long-axis images (with four parallel
      tags) were generated, and endocardial and epicardial borders were manually
      traced. By integration of the short- and long-axis images, 3D reconstruction of
      the LV tracking points from end diastole to end systole was obtained. Data from
      the midventricular two short-axis image slices were analyzed. These were then
      divided into anterior, lateral, posterior, and septal regions. Circumferential
      and longitudinal shortening were then calculated from the endocardial and
      epicardial tag intersection points. Wall thickness and thickening were calculated
      by the 3D volume-element approach. An eccentricity index (EI), the ratio of
      septum-to-free-wall to anteroposterior diameters, was used to describe the shape
      of the LV cavity. The regional curvature was also measured. The RVPO group was
      characterized by flattening of the septum and LV lateral wall, decreased EI
      reflecting the distorted LV shape, altered distribution of endocardial
      circumferential shortening, and preserved ejection fraction. Changes in EI
      closely correlated with the septal curvature. The EI was smaller at end systole,
      reflecting further shape distortion relative to end diastole. Reduced myocardial
      performance, as measured by wall thickening and circumferential and longitudinal
      shortening fractions, was observed for the septum. A reduction in endocardial
      circumferential shortening of the septal and lateral walls was directly related
      to the end-systolic EI. In addition, whereas for healthy subjects a linear
      relation between area ejection fraction and endocardial circumferential
      shortening was observed, in RVPO patients a curvilinear (quadratic) relation was
      observed. CONCLUSIONS: In patients with RVPO, compared with healthy subjects, the
      septal function was reduced, as evidenced by reduced thickening and shortening
      fractions. The distortion in LV cavity at end systole due to the flattening of
      the septum contributes to preserved systolic ventricular function and nonuniform
      distribution in endocardial circumferential shortening.

PMID- 7729023
TI  - Long-term temporal patterns of ventricular tachyarrhythmias.
AB  - BACKGROUND: Technological limitations have precluded investigation of long-term
      temporal patterns of ventricular tachyarrhythmia recurrences. Newer implantable
      cardioverter-defibrillators permit such analyses by accurately recording the time
      and date of tachycardia detections during long-term follow-up. This study tests
      the hypothesis that ventricular tachycardia occurrences are randomly distributed
      over time in individual patients. METHODS AND RESULTS: The time and date of 727
      episodes of ventricular tachyarrhythmias were recorded from the data logs of 31
      patients with implantable cardioverter-defibrillators followed for a median of
      177 days (range, 7 to 782 days). All patients had three or more ventricular
      tachycardia detections and no detections from causes other than ventricular
      arrhythmias. In 28 of 31 patients, the distribution of the interdetection time
      intervals during follow-up differed significantly (all P < .01) from an
      exponential model distribution of interdetection intervals that assumed that
      detections were equally likely to occur at any time during follow-up (random).
      The Kolmogorov-Smirnov goodness-of-fit test was used to compare sample and model
      distributions. In each patient, the nonrandom distributions resulted from a
      preponderance of interdetection time intervals that were shorter than predicted
      by the random model, resulting in a temporal clustering of arrhythmic events. The
      interdetection interval was < or = 1 hour and < or = 91 hours for 55% and 78% of
      all intervals, respectively. When only those episodes receiving shock or
      antitachycardia pacing therapy were analyzed, 25 of 29 patients still manifested
      nonrandom distributions (all P < .01). When only episodes with tachycardia rates
      > 240 beats per minute were analyzed, 11 of 13 patients manifested non-random
      distributions (all P < .01). CONCLUSIONS: Ventricular tachycardia detections and
      delivered antitachycardia therapies by implantable cardioverter-defibrillators
      are nonrandomly distributed throughout long-term follow-up in the majority of
      patients. The temporal clustering of these arrhythmic events may allow preemptive
      antiarrhythmic therapy and should be considered in the design of therapy based on
      suppression of spontaneous ventricular arrhythmias to statistically derived end
      points.

PMID- 7729024
TI  - Relation between repolarization and refractoriness during programmed electrical
      stimulation in the human right ventricle. Implications for ventricular
      tachycardia induction.
AB  - BACKGROUND: Although programmed electrical stimulation is widely used for
      provoking sustained ventricular tachycardia (VT), the mechanism by which
      repetitive extrastimulation evokes VT is still little understood. Specifically,
      it is not clear why several closely coupled extrastimuli are frequently required
      to induce VT. Although regularly paced human ventricular myocardium exhibits a
      near constant relation between myocardial repolarization and refractoriness, the
      effect of repetitive extrastimulation on the relation between repolarization and
      excitability in the human heart and its relevance for arrhythmia induction by
      programmed stimulation are unknown. We hypothesized that the induction of VT by
      repetitive extrastimulation is facilitated by an altered relation between
      repolarization and refractoriness, and this leads to disturbances in ventricular
      impulse propagation, which trigger the onset of VT. METHODS AND RESULTS: Twenty
      one patients undergoing routine electrophysiological study were paced from the
      right ventricular apex and outflow tract endocardium with monophasic action
      potential-pacing catheters placed at both sites simultaneously Monophasic action
      potential durations (APDs) and effective refractory periods (ERPs) were measured
      simultaneously at each site, during regular stimulation (S1-S1) at 400-ms cycle
      length and during three consecutive extrastimuli (S2 through S4) at the closest
      coupling intervals at which all three extrastimuli still resulted in capture.
      Measurements further included the repolarization level at which the earliest
      capture occurred, the ratio between ERP and APD, and the propagation time between
      the pacing and distant recording site. APD and ERP both shortened progressively
      with each extrastimulus. APD at 90% repolarization decreased from a baseline (S1)
      of 238.1 +/- 19.7 ms by 14.9% at S2, 18.9% at S3, and 22.9% at S4 (P < .0001, S1
      versus S4). ERP decreased from 233.1 +/- 19.7 ms (S1) to 180.0 +/- 41.9 ms (S3)
      (P < .0001, S1 versus S3). While ERP shortening occurred mainly on the basis of
      APD shortening, there was an additional factor that contributed to ERP shortening
      independent of APD shortening. Each consecutive extrastimulus was able to elicit
      a propagated response at earlier repolarization levels than the previous one: the
      earliest capture for S2 occurred at 85.5 +/- 10.2% of complete repolarization,
      for S3 at 83.9 +/- 10.5%, and for S4 at 78.4 +/- 11.2% (P < .05 for S2 versus S3;
      P < .05 for S3 versus S4; P < .01 for S2 versus S4). This progressive
      "encroachment" of the earliest capture stimulus onto the preceding repolarization
      phase (at progressively less repolarized levels) correlated with a progressive
      delay of impulse propagation between the pacing site and the second recording
      site: propagation time increased from baseline (S1) by 10.5 +/- 1.3% with S2 to
      19.0 +/- 1.6% with S3 and to 22.5 +/- 2.8% with S4 (P < .05, S4 versus S1). VT
      was induced in 11 of 21 patients. Nine of these had VT induced only when
      significant encroachment of extrastimuli on the preceding repolarization phase (<
      81.3 +/- 7.0%) and associated conduction slowing (> 16.6 +/- 1.8%) were present.
      CONCLUSIONS: Repetitive extrastimulation not only shortens APD and subsequently
      ERP but also alters the ERP/APD relation by allowing capture to occur at
      progressively less complete repolarization levels. This progressive encroachment
      onto the preceding repolarization phase is associated with impaired impulse
      propagation and a high incidence of VT induction. This may help explain how
      repetitive, closely coupled extrastimulation induces ventricular tachycardia in
      the human heart.

PMID- 7729025
TI  - Effect of subendocardial resection on sinus rhythm endocardial electrogram
      abnormalities.
AB  - BACKGROUND: Patients with sustained ventricular tachycardia after acute
      myocardial infarction frequently have characteristic abnormalities of left
      ventricular endocardial electrical activity, including fractionated (prolonged,
      multicomponent, low-amplitude), split (having discrete widely separated
      deflections), and late (extending after the end of the QRS complex) electrograms.
      The exact cause and source of these electrograms are not clear. METHODS AND
      RESULTS: In this study, endocardial electrograms from 18 patients were recorded
      with a 20-electrode array from the same area immediately before and immediately
      after resection of subendocardial tissue at the time of surgery for ventricular
      tachycardia. Electrograms could be compared before and after resection from 298
      of 360 (83%) of the electrodes. Before resection, split electrograms were present
      in 130 (44%) and late components in 81 (27%) of the recordings. Recordings made
      after resection showed fewer abnormalities, including complete absence of split
      electrograms as well as all previously recorded late components (P < .02). Mean
      electrogram amplitude increased from 0.5 +/- 0.8 to 1.0 +/- 1.6 mV (P < .0001)
      because of removal of the attenuating effect of endocardial scar; mean duration
      decreased from 112 +/- 38 to 65 +/- 27 ms (P < .0001) mainly because of loss of
      late and split components. Overall electrogram contour was very similar aside
      from these changes. CONCLUSIONS: These data show that (1) some of the signal
      recorded on the endocardial surface is derived from deeper tissue layers and (2)
      split and late electrogram components appear to be generated by cells in the
      superficial endocardial layers, since they are eradicated by removal of this
      tissue. These findings correspond well with previous histological studies of
      resection specimens that show bundles of surviving muscle cells separated by
      layers of dense scar that act as an insulator.

PMID- 7729026
TI  - Delayed improvement in exercise capacity with restoration of sinoatrial node
      response in patients after combined treatment with surgical repair for organic
      heart disease and the Maze procedure for atrial fibrillation.
AB  - BACKGROUND: Although the Maze procedure successfully restores sinus rhythm in
      patients with heart disease and atrial fibrillation, it is still uncertain
      whether an addition of the Maze procedure in cardiac surgery is beneficial for
      exercise performance of the patients after surgery. METHODS AND RESULTS: The Maze
      procedure was performed in 25 patients (age, 37 to 70 years) during valve surgery
      (18 patients) or closure of atrial septal defect (7 patients). A cardiopulmonary
      exercise test using ramp incremental protocol (15 W/min) was performed before and
      1 month, 6 months, and 1 year after surgery. Sinus conversion was obtained in 23
      of 25 patients 1 month after surgery. However, sinoatrial (SA) node response to
      exercise was attenuated by surgery: Mean heart rate (HR) was 83 +/- 13/min at
      rest, 94 +/- 13/min at 60 W, and 107 +/- 17/min at peak exercise. Peak oxygen
      uptake (PVO2) was unchanged at this period (before, 17.6 +/- 4.5 mL.min-1.kg-1; 1
      month after, 17.5 +/- 4.2 mL.min-1.kg-1). Thereafter, SA node response was
      restored 6 months after surgery: Mean HR was 84 +/- 13/min at rest, 104 +/-
      16/min at 60 W, and 130 +/- 20/min at peak exercise (P < .01 versus 1 month).
      PVO2 was also improved at this period (20.7 +/- 4.0 mL.min-1.kg-1, P < .01). The
      increase in PVO2 from 1 month to 6 months after surgery was correlated with the
      increase in peak HR (y = 0.73x +/- 3.6, r = .79). There were no further changes
      in heart rate response or PVO2 from 6 months to 1 year after surgery.
      CONCLUSIONS: Atrial fibrillation was successfully treated by combined treatment
      with surgical repair for organic heart disease and the Maze procedure. However,
      SA node response to exercise was attenuated early after surgery. Thus, exercise
      capacity was improved at the late phase after surgery, which was related to the
      extent of restoration in SA node response.

PMID- 7729027
TI  - Effect of body size, ponderosity, and blood pressure on left ventricular growth
      in children and young adults in the Bogalusa Heart Study.
AB  - BACKGROUND: The measurement of left ventricular mass (LVM) is important because
      individuals with increased LVM are at increased risk for cardiovascular diseases,
      including myocardial infarction and congestive heart failure. There are limited
      longitudinal data on the acquisition of LVM in children and young adults and the
      relative importance of sex, growth, excess body weight, and blood pressure (BP)
      on change in LVM. METHODS AND RESULTS: The study cohort consisted of a cross
      section of 160 healthy children and young adults 9 to 22 years of age at first
      exam in the biracial community of Bogalusa, La. All had stable BP levels recorded
      over a 2- to 3-year period. Repeated examinations were performed 4 to 5 years
      apart. At each exam, 6 BPs were obtained with a mercury sphygmomanometer by
      trained examiners. The mean of the observations was used, with the fourth
      Korotkoff phase serving as the measure of diastolic BP. Anthropometric data,
      including height (HT), weight (WT), and triceps skin fold thickness (TSF), were
      also obtained, and M-mode echocardiograms were performed. Ponderal index (PI =
      WT/HT3) was used as a measure of weight-for-height. Tracking of HT (r = .68 to
      .76), WT (r = .73 to .82), PI (r = .77 to .89), TSF (r = .70 to .80), BP (r = .47
      to .60), and LVM (r = .40 to .70) was strong in both sexes (P < .0001). LVM
      indexed for linear growth (LVM/HT2.7) tracked in females (r = .56, P < .0001) but
      not in males. In univariate cross-sectional analyses, LVM/HT2.7 correlated with
      WT, PI, and TSF in both sexes (r = .21 to .60, P < .05) and with systolic BP
      (SBP) in females (r = .23, P < .05). WT was the only independent correlate of
      LVM/HT2.7 in both sexes in multivariate cross-sectional analysis in a model
      containing age, SBP, WT, and TSF as independent variables (r2 = .08 to .28, P <
      .02). In longitudinal univariate analyses, initial measurements of WT, PI, and
      TSF predicted final LVM/HT2.7 in both sexes (r = .28 to .56, P < .01), and SBP
      was significant for females (r = .27, P < .05). In multivariate analyses, initial
      WT was associated with final LVM and LVM/HT2.7 in both sexes (r2 = .27 to .54, P
      < .01). Finally, baseline LVM correlated with final SBP in both sexes (r = .21 to
      .27, P < .05), and initial LVM/HT2.7 correlated with final SBP in females (r =
      .26, P < .05) with a trend for males (r = .17). CONCLUSIONS: These data indicate
      that linear growth is the major determinant of cardiac growth in children and
      that excess weight may lead to the acquisition of LVM beyond that expected from
      normal growth. Increased mass may also precede the development of increased BP.
      The development of obesity may therefore be a significant, and possibly
      modifiable, risk factor for developing left ventricular hypertrophy and
      hypertension, risk factors for cardiovascular morbidity and mortality.

PMID- 7729028
TI  - In vivo gene transfer into injured carotid arteries. Optimization and evaluation
      of acute toxicity.
AB  - BACKGROUND: Adenoviral vectors are very attractive agents for use in in vivo
      arterial gene transfer. In a previous study, we demonstrated high-efficiency
      adenovirus-mediated gene transfer into medial smooth muscle cells of balloon
      injured rat carotid arteries. We now further characterize this system by
      investigating the reproducibility of recombinant gene expression, the presence of
      acute adenovirus-associated toxicity in the vessel wall, and the optimal virus
      concentration for transduction. METHODS AND RESULTS: Balloon-injured rat carotid
      arteries were incubated with (1) an adenovirus expressing a beta-galactosidase
      gene (Av1LacZ4), (2) a related adenovirus without the recombinant gene (Addl312),
      or (3) control solutions. Recombinant gene expression was determined 3 days after
      gene transfer by measurement of beta-galactosidase activity in vessel extracts
      and by counting of smooth muscle cells in microscopic sections that were
      histochemically stained to detect recombinant beta-galactosidase activity.
      Adenovirus-associated toxicity was assessed in microscopic cross sections by
      counting of total smooth muscle cell nuclei in the media (to identify cell loss)
      and characterization of medial cellular infiltrates with histochemical stains for
      specific inflammatory cells (neutrophils, lymphocytes, macrophages, and
      monocytes). Maximum recombinant gene expression after incubation with Av1LacZ4
      was produced by virus concentrations ranging from 2 x 10(10) to 5 x 10(10) plaque
      forming units (pfu)/mL. Surprisingly, use of a higher concentration of Av1LacZ4
      virus (1 x 10(11) pfu/mL) resulted in loss of recombinant gene expression. In
      addition, infusion of either Av1LacZ4 or Addl312 at 1 x 10(11) pfu/mL resulted in
      statistically significant decreases in medial smooth muscle cell number (53%
      decrease, P < 0.01 for Av1LacZ4; 39% decrease, P < .05 for Addl312) compared with
      vessels infused with control solution. This decrease in smooth muscle cell number
      was not present after the infusion of virus at lower concentrations. The number
      of neutrophils in vessel cross sections was significantly increased (fivefold; P
      < .05) after infusion of Av1LacZ4 at 1 x 10(11) pfu/mL compared with vessels
      infused with control solution. Lymphocytes, macrophages, and monocytes were
      present only in low numbers in all vessel cross sections and were not increased
      consequent to adenovirus infusion. CONCLUSIONS: This model of focal in vivo
      adenovirus-mediated gene transfer into the media of injured arteries is highly
      reproducible and allows high-level recombinant gene expression over a fairly
      narrow range of virus concentrations. Acute adenovirus-associated tissue
      toxicity, as demonstrated by medial smooth muscle cell loss and neutrophilic
      infiltrates, places an upper limit on virus concentration and associated
      recombinant gene expression and suggests the presence of a "window" of virus
      concentration in which either therapeutic or biological effects of recombinant
      genes can be studied in the absence of associated acute toxicity.

PMID- 7729029
TI  - Age and hypertension differently affect coronary contractions to endothelin-1,
      serotonin, and angiotensins.
AB  - BACKGROUND: Endothelium-derived substances and the renin-angiotensin system are
      important regulators of vascular tone. This study was designed to evaluate the
      effects of age and hypertension on vascular function of rat coronary arteries.
      METHODS AND RESULTS: Rings of the left anterior descending coronary artery were
      isolated from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR)
      at 12 (younger) and 72 (older) weeks of age and suspended in myographs (37
      degrees C, 95% O2/5% CO2) for isometric tension recording. Systolic blood
      pressure was higher in SHR than in WKY rats (P < .05) but was unaffected by age
      in both strains. Active wall tension to KCl 100 mmol/L (mN/mm) was decreased in
      younger (0.28 +/- 0.03, n = 9) and older SHR (0.49 +/- 0.06, n = 13) compared
      with age-matched WKY rats (0.87 +/- 0.05, n = 9 and 1.51 +/- 0.11, n = 11,
      respectively, P < .05). In both strains, active wall tension to endothelin-1 and
      serotonin increased with age (n = 6 to 10, P < .05) but was decreased in younger
      and older SHR compared with WKY rats (P < .05). Active wall tension induced by
      angiotensin I 10(-7) mol/L was increased in older SHR (0.19 +/- 0.04, n = 7)
      compared with younger SHR (0.04 +/- 0.01, n = 9) but was similar in younger and
      older WKY rats (0.10 +/- 0.02 versus 0.15 +/- 0.03, n = 6 to 9) and younger SHR.
      In younger WKY rats and SHR, pretreatment of coronary arteries with benazeprilat
      10(-5) mol/L (n = 5 for each) almost completely abolished the contractions to
      angiotensin I 10(-7) mol/L. Active wall tension to angiotensin II 10(-7) mol/L
      was comparable in all four groups, but compared with the contraction to KCl 100
      mmol/L, the response was already increased in younger SHR (29 +/- 3%, n = 9)
      compared with the younger WKY rats (14 +/- 3%, n = 9, P < .05), but it was
      unaffected by age in both strains. In vitro treatment of younger WKY rat and SHR
      coronary arteries with the nonpeptide angiotensin II (AT1) receptor antagonist
      valsartan 10(-5) mol/L (n = 3 for each) fully suppressed contractions to
      angiotensin II 10(-7) mol/L. In contrast, endothelium-independent relaxations to
      the nitrovasodilator sodium nitroprusside, endothelium-dependent relaxations to
      acetylcholine, and endothelium-dependent contractions to N omega-nitro-L-arginine
      methyl ester were comparable in all four groups of rats. CONCLUSIONS: In summary,
      in rat coronary arteries, contractile responses to endothelin-1, serotonin, and
      KCl increase with age but are decreased by hypertension. In contrast, the L
      arginine/nitric oxide pathway remains unaffected. The contractions to angiotensin
      I markedly increased with increasing duration of hypertension in the SHR only.
      Despite overall reduced contractile responses of SHR coronary arteries,
      contractions to angiotensin II were maintained. Hence, aging and hypertension
      affect contractile responses of rat coronary arteries to vasoconstrictor agonists
      differently.

PMID- 7729030
TI  - Left ventricular contractility predicts how the end-diastolic pressure-volume
      relation shifts during pacing-induced ischemia in dogs.
AB  - BACKGROUND: Two types of ischemia, pacing-induced and coronary occlusion-induced,
      have different effects on left ventricular diastolic properties. During pacing
      induced ischemia, the diastolic pressure-volume relation is said to shift upward,
      whereas during coronary occlusion, it is said to shift rightward or downward.
      However, recent studies have shown that the relation can shift in any direction
      during both types of ischemia. The purpose of this study was to identify
      determinants of the shift of the end-diastolic pressure-volume relation (EDPVR)
      during pacing-induced ischemia. METHODS AND RESULTS: We retrospectively analyzed
      46 pacing-induced ischemia experiments performed in 15 open-pericardium
      anesthetized dogs. Pacing ischemia was induced by constricting left anterior
      descending and left circumflex coronary arteries and pacing the left atrium at
      150 to 180 beats per minute for 3 minutes. Left ventricular volume was measured
      with a conductance catheter. Hemodynamics were recorded during baseline, coronary
      stenosis, rapid pacing, and pacing-induced ischemia (immediately after rapid
      pacing). For each condition, hemodynamics were recorded in steady state and then
      during a brief inferior vena caval occlusion (except for during rapid pacing) to
      obtain left ventricular end-diastolic and end-systolic pressure-volume relations.
      The shift of the EDPVR from coronary stenosis to pacing-induced ischemia was
      assessed by an upward shift index (end-diastolic pressure during pacing-induced
      ischemia minus the pressure during coronary stenosis at the largest end-diastolic
      volume common to both conditions, SI-S) and a rightward shift index (the largest
      end-diastolic volume during pacing-induced ischemia minus the largest volume
      during coronary stenosis, delta EDVI-S). The index of left ventricular
      contractility, the end-systolic elastance (Ees), or the slope of the dP/dtmax-end
      diastolic volume relation (dE/dtmax) during pacing-induced ischemia was the
      strongest determinant of the magnitude of SI-S and delta EDVI-S and thus of the
      shift of the EDPVR. As Ees or dE/dtmax decreased, SI-S decreased and delta EDVI-S
      increased. CONCLUSIONS: Our results suggest that left ventricular contractility
      is the best determinant of the shift of the EDPVR during pacing-induced ischemia.
      The more left ventricular contractility decreases, the more the EDPVR shifts
      downward and rightward.

PMID- 7729031
TI  - Fundamental limitations of [18F]2-deoxy-2-fluoro-D-glucose for assessing
      myocardial glucose uptake.
AB  - BACKGROUND: The glucose tracer analog [18F]2-deoxy-2-fluoro-D-glucose (FDG) is
      widely used for assessing regional myocardial glucose metabolism in vivo. The
      reproducibility of this method has recently been questioned because of a
      discordant affinity of hexokinase for its substrates glucose and 2-deoxyglucose.
      We therefore compared rates of glucose utilization simultaneously with tissue
      time-activity curves of FDG uptake before and after changes in the physiological
      environment of the heart. METHODS AND RESULTS: Isolated working rat hearts were
      perfused for 60 minutes with recirculating Krebs buffer containing glucose (10
      mmol/L), FDG (1 microCi/mL), [2-3H]glucose (0.05 microCi/mL), and [U-14C]2
      deoxyglucose (2-DG; 0.025 microCi/mL). Myocardial glucose uptake was measured by
      tracer ([2-3H]glucose) and tracer analog methods (FDG and 2-DG) before and after
      the addition of either insulin (1 mU/mL), epinephrine (1 mumol/L), lactate (40
      mmol/L), or D,L-beta-hydroxybutyrate (40 mmol/L) at 30 minutes of perfusion and
      after acute changes in cardiac workload. Under steady-state conditions,
      myocardial rates of glucose utilization as measured by tritiated water (3H2O)
      production from metabolism of [2-3H]glucose, FDG uptake, and 2-DG retention were
      linearly related. The addition of competing substrates decreased glucose
      utilization immediately. The addition of insulin increased the rate of glucose
      utilization as measured by the glucose tracer but not as measured by the tracer
      analogs. The ratio of 3H2O release/myocardial FDG uptake increased by 111% after
      the addition of insulin, by 428% after the addition of lactate, and by 232% after
      the addition of beta-hydroxybutyrate. Epinephrine increased rates of glucose
      utilization and contractile performance, whereas there was no increase in glucose
      uptake with a comparable increase in workload alone. There was no change in the
      relation between the glucose tracer and the tracer analog either with epinephrine
      or with acute changes in workload. CONCLUSIONS: The uptake and retention of FDG
      in heart muscle is linearly related to glucose utilization only under steady
      state conditions. Addition of insulin or of competing substrates changes the
      relation between uptake of the glucose tracer and FDG. These observations
      preclude the determination of absolute rates of myocardial glucose uptake by the
      tracer analog method under non-steady-state conditions.

PMID- 7729032
TI  - Experimental ablation of outflow tract muscle with a thermal balloon catheter.
AB  - BACKGROUND: Pulmonary balloon valvuloplasty has been performed in selected
      patients with tetralogy of Fallot as an alternative to surgical palliation; this
      technique is limited, however, by the fact that the balloon has little effect on
      the dynamic, muscular contribution to outflow tract obstruction. In an
      experimental model, we used a new thermal balloon catheter to ablate right
      ventricular outflow tract muscle. We evaluated the acute efficacy and muscle
      ablation parameters of this technology and its effects after myocardial healing.
      METHODS AND RESULTS: A prototype electrolyte-filled balloon catheter, heated by
      radiofrequency energy, was constructed. Studies were conducted to determine the
      optimum electrolyte solution needed to minimize balloon heating time with an
      unmodified, commercially available radiofrequency generator. In vivo ablations of
      right ventricular outflow tract muscle with the thermal balloon were performed in
      lambs that were divided into three groups (n = 5 each) according to the duration
      of thermal energy delivery (20, 40, and 60 seconds, respectively). Ablated lesion
      volume increased (460 +/- 63 to 1156 +/- 256 mm3) as the energy delivery time
      increased (20 to 60 seconds) and was correlated with delivered energy,
      temperature integral, and maximum epicardial surface temperature (r = .85, .82,
      and .72, respectively). All five lesions in the 60-second group showed an acute
      decrease of the wall thickness. Additional in vivo ablations were performed in 6
      animals in which survival studies showed muscle thinning, healing by fibrosis,
      and no evidence of aneurysm formation. CONCLUSIONS: Thermal energy can be used
      with a balloon catheter delivery system to ablate myocardium. This study suggests
      that this energy delivery technology might be useful for relief of muscular
      outflow tract obstruction and that further studies are warranted.

PMID- 7729033
TI  - Nonstationary vortexlike reentrant activity as a mechanism of polymorphic
      ventricular tachycardia in the isolated rabbit heart.
AB  - BACKGROUND: Ventricular tachycardia may result from vortexlike reentrant
      excitation of the myocardium. Our general hypothesis is that in the structurally
      normal heart, these arrhythmias are the result of one or two nonstationary three
      dimensional electrical scroll waves activating the heart muscle at very high
      frequencies. METHODS AND RESULTS: We used a combination of high-resolution video
      imaging, electrocardiography, and image processing in the isolated rabbit heart,
      together with mathematical modeling. We characterized the dynamics of changes in
      transmembrane potential patterns on the epicardial surface of the ventricles
      using optical mapping. Image processing techniques were used to identify the
      surface manifestation of the reentrant organizing centers, and the location of
      these centers was used to determine the movement of the reentrant pathway. We
      also used numerical simulations incorporating Fitzhugh-Nagumo kinetics and
      realistic heart geometry to study how stationary and nonstationary scroll waves
      are manifest on the epicardial surface and in the simulated ECG. We present
      epicardial surface manifestations (reentrant spiral waves) and ECG patterns of
      nonstationary reentrant activity that are consistent with those generated by
      scroll waves established at the right and left ventricles. We identified the
      organizing centers of the reentrant circuits on the epicardial surface during
      polymorphic tachycardia, and these centers moved during the episodes. In
      addition, the arrhythmias that showed the greatest movement of the reentrant
      centers displayed the largest changes in QRS morphology. The numerical
      simulations showed that stationary scroll waves give rise to monomorphic ECG
      signals, but nonstationary meandering scroll waves give rise to undulating ECGs
      characteristic of torsade de pointes. CONCLUSIONS: Polymorphic ventricular
      tachycardia in the healthy, isolated rabbit heart is the result of either a
      single or paired ("figure-of-eight") nonstationary scroll waves. The extent of
      the scroll wave movement corresponds to the degree of polymorphism in the ECG.
      These results are consistent with our numerical simulations that showed
      monomorphic ECG patterns of activity for stationary scroll waves but polymorphic
      patterns for scroll waves that were nonstationary.

PMID- 7729034
TI  - A novel method for treatment of abdominal aortic aneurysms using percutaneous
      implantation of a newly designed endovascular device.
AB  - BACKGROUND: Percutaneous implantation of a stent to bridge abdominal aortic
      aneurysm (AAA) may provide an alternative to surgical reconstruction in patients
      with this serious disorder. We developed a self-expandable, stainless steel,
      woven mesh endovascular device with a delivery catheter and studied its efficacy
      in a canine model of AAA. METHODS AND RESULTS: Infrarenal AAAs were created
      surgically in eight adult dogs using autologous tissue. Two types of endovascular
      stents were used in this study; a plain or uncovered stent, about 14 mm in
      diameter in the unconstrained configuration, and a covered stent, coated by
      porous polyurethane, about 16 mm in diameter. All stents were successfully placed
      on the first attempt. Aortograms revealed a mean aneurysm diameter of 1.86 +/-
      0.47 cm, an average of 70% larger than the reference aortic lumen before stent
      placement. After stent placement, aortograms showed that the aneurysmal cavity
      disappeared completely in three dogs treated with a covered stent and that the
      aortic blood flow into the cavity markedly reduced, with faint contrast filling
      the cavity in the remaining five dogs treated with an uncovered stent. The
      uncovered stent was intentionally placed across the major arterial branches in
      two dogs. No acute complications were encountered at the time of stent placement.
      Two dogs were killed shortly after the procedure for immediate evaluation of the
      device, which was found to be in place and patent. One dog in which a covered
      stent was placed was euthanized 2 1/2 weeks later because of paraplegia secondary
      to a spinal cord infarction noted 48 hours after stent placement. Postmortem
      study revealed thrombus occluding the stent lumen. The remaining five dogs
      tolerated the devices well and completed 4 weeks of follow-up. Premortem
      aortograms showed no residual aneurysmal cavity in four dogs and only a small
      cavity in one dog that had received an uncovered stent. All stents were fully
      patent with no thrombus and were either completely or partially surfaced by
      neointima. Importantly, the major arterial branches over which the uncovered
      stents were placed were widely patent without obstruction by neointima.
      CONCLUSIONS: This study demonstrates the feasibility of percutaneous implantation
      of this new device and its effectiveness in the treatment of surgically created
      AAA in our canine model. The covered stent was able to exclude AAA immediately
      upon deployment and is of potential value in the emergency treatment of leaking
      AAAs. The uncovered stent appears to safely bridge branch arteries as well as
      significantly reduce the angiographic size of the aneurysm and may be useful in
      the elective therapy of AAAs. These results are promising, and future clinical
      trials to investigate the safety and efficacy of this device in humans are
      warranted.

PMID- 7729035
TI  - Morphological observations on the pathogenetic process of transposition of the
      great arteries induced by retinoic acid in mice.
AB  - BACKGROUND: The pathogenesis of complete transposition of the great arteries
      (TGA) is still controversial because useful animal models have not been
      established. We previously reported that all-trans retinoic acid induced complete
      TGA at a high proportion in mice. The aim of the present study was to clarify the
      morphogenesis of the cardiac outflow tract in the retinoic acid-treated embryos
      destined to develop TGA. METHODS AND RESULTS: We first examined the morphology of
      TGA in mouse fetuses treated with retinoic acid to establish an animal model of
      TGA (experiment 1) and then examined the retinoic acid-treated embryonic hearts
      by means of ink injection and histology (experiment 2). All mouse fetuses and
      embryos showed visceroatrial situs solitus and d-ventricular loop. In experiment
      1, among 45 embryos treated with retinoic acid 70 mg/kg at day 8.5 of gestation,
      35 (78%) had TGA and 3 (6.7%) had a double-outlet right ventricle with a
      subpulmonary ventricular septal defect. In experiment 2, all hearts already
      exhibited d-loop at gestation day 8.5. At gestation day 9.5, conus swellings,
      composed of acellular cardiac jelly, where hypoplastic, and the conotruncal
      cavity was nonspiral or tubular. At gestation day 11.0, aberrant conus swellings
      located anteroposteriorly to give a straight orientation to the conotruncal
      cavity. At gestation day 12.0, side-by-side great arteries were transposed in
      that the aorta arose from the right ventricle and the pulmonary artery arose
      above the interventricular foramen. CONCLUSIONS: These results suggest that a
      reproducible animal model of TGA can be produced in mice by treatment with
      retinoic acid; that there was no loop anomaly, such as an A-loop or L-loop, in
      our model; and that hypoplasia of the conus swellings appears to be the primary
      event leading to TGA.

PMID- 7729036
TI  - Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics.
AB  - The clinical events resulting from atherosclerosis are directly related to the
      oxidation of lipids in LDLs that become trapped in the extracellular matrix of
      the subendothelial space. These oxidized lipids activate an NF kappa B-like
      transcription factor and induce the expression of genes containing NF kappa B
      binding sites. The protein products of these genes initiate an inflammatory
      response that initially leads to the development of the fatty streak. The
      progression of the lesion is associated with the activation of genes that induce
      arterial calcification, which changes the mechanical characteristics of the
      artery wall and predisposes to plaque rupture at sites of monocytic infiltration.
      Plaque rupture exposes the flowing blood to tissue factor in the lesion, and this
      induces thrombosis, which is the proximate cause of the clinical event. There
      appear to be potent genetically determined systems for preventing lipid
      oxidation, inactivating biologically important oxidized lipids, and/or modulating
      the inflammatory response to oxidized lipids that may explain the differing
      susceptibility of individuals and populations to the development of
      atherosclerosis. Enzymes associated with HDL may play an important role in
      protecting against lipid oxidation in the artery wall and may account in part for
      the inverse relation between HDL and risk for atherosclerotic clinical events.

PMID- 7729037
TI  - Images in cardiovascular medicine. Cardiac sarcoidosis. 67Ga imaging and
      histology.

PMID- 7729038
TI  - Evaluation of diagnostic procedures.

PMID- 7729039
TI  - Morrow septal myectomy for patients with HOCM.

PMID- 7729040
TI  - Tartrate-resistant acid phosphatase as a marker of bone resorption.

PMID- 7729041
TI  - Multiple mechanisms account for genomic instability and molecular mutation in
      neoplastic transformation.
AB  - Neoplastic cells typically possess numerous genomic mutations and chromosomal
      aberrations, including point mutations, gene amplifications and deletions, and
      replication errors. Acquisition of such genomic instability may represent an
      early step in the process of carcinogenesis. Proteins involved in DNA
      replication, DNA repair, cell cycle progression, and others are all components of
      complex overlapping biochemical pathways that function to maintain cellular
      homeostasis. Therefore, mutational alteration of genes encoding proteins involved
      in these cellular processes could contribute to genomic instability. Loss of
      normal cellular mechanisms that guard against genomic mutation and the ensuing
      genomic instability might lead to accumulation of multiple stable mutations in
      the genome of affected cells, perhaps resulting in neoplastic transformation when
      some critical number of transformation-related target genes become damaged. Thus,
      interactions of fundamental cellular processes play significant roles in
      sustaining cellular normality, and alteration of any of these homeostatic
      processes could entrain cells to the progressive genomic instability and
      phenotypic evolution characteristic of carcinogenesis. Here, we discuss possible
      molecular mechanisms governing DNA mutation and genomic instability in
      genetically normal cells that might account for the acquisition of genomic
      instability in somatic cells, leading to the development of neoplasia. These
      include (a) molecular alteration of genes encoding DNA repair enzymes, (b)
      molecular alteration of genes responsible for cell-cycle control mechanisms, and
      (c) direct molecular alteration of dominantly transforming cellular
      protooncogenes. We also discuss normal cellular processes involved with DNA
      replication and repair that can contribute to the mutational alteration of
      critical genes: e.g., slow repair of damaged DNA in specific genes, and the
      timing of normal gene-specific replication.

PMID- 7729042
TI  - Chromatographic evaluation of minor hemoglobins: clinical significance of
      hemoglobin A1d, comparison with hemoglobin A1c, and possible interferences.
AB  - Using an HPLC procedure, we evaluated > 10 minor hemoglobins (Hbs) in healthy
      adults, individuals on long-term aspirin therapy, diabetic subjects, and uremic
      patients. Hb A1c and Hb A1d3 were the most abundant and important minor Hb
      components, respectively, accounting for 4.10% +/- 0.50% and 3.46% +/- 0.43% of
      total Hb in 361 healthy subjects. Acetylated Hb A was a potential interferent in
      the measurement of Hb A1c. The amounts of both Hb A1d3 and Hb A1carb were
      significantly increased in uremic patients, indicating that these Hb adducts may
      be carbamylated. There was a significant correlation (r = 0.69, P < 0.0001)
      between the amounts of Hb A1d3 and plasma urea in uremic patients. Nonuremic
      subjects were clearly separated from uremic patients with regard to the Hb A1d3
      content of their total Hb. Our data suggest that Hb A1d3 is useful for assessment
      of the uremic state and that the combination of Hb A1c and Hb A1d3 could be well
      suited for simultaneous control of carbohydrate and urea metabolism.

PMID- 7729043
TI  - Automated dibucaine number measurement with DuPont Dimension ES and AR analyzers.
AB  - We report a fully automated method for determining dibucaine number (DN) in a
      single-run procedure involving Dimension cholinesterase (CHE) Flex pseudo-(P)CHE
      reagents. The method was developed and optimized with the "open channels" and
      "kinetic" software facilities of the Dimension-ES instrument, where the DN is
      calculated automatically by an algorithm from the ratio of the uninhibited and
      inhibited rates, measured bichromatically, from a single analysis. The protocol
      was satisfactorily assessed for substrate depletion, linearity, reagent
      stability. and the effects of different dibucaine concentrations. Validation was
      performed across a range of CHE activities (1.5-22 kU/L) representing the three
      main genotypes, UU, UA, and AA. The respective DNs (mean +/- SD), determined on
      the Dimension-ES, were 82.0 +/- 1.6 (n = 32), 71.0 +/- 3.1 (n = 10), and 23.0 +/-
      2.7 (n = 14), with corresponding imprecisions (CV) of 0.3%, 0.6%, and 5.2%
      (intraassay) and 0.7%, 0.7%, and 8.6% (interassay). Comparisons with reference
      (x) laboratory values and the DuPont aca (x') procedure (n = 53) gave regression
      equations of: y = 0.88x + 11.2, r = 0.99, and y = 0.85x' + 11.9, r = 0.99. A
      separate trial conducted with a Dimension-AR instrument gave similar
      performances. We conclude that the new DN method is fast, efficient, and
      appropriate for clinical use.

PMID- 7729044
TI  - Bone alkaline phosphatase and height velocity in short normal children undergoing
      growth-promoting treatments: longitudinal study.
AB  - We studied the temporal and quantitative relation between bone alkaline
      phosphatase (ALP) and height velocity in 62 short normal children as part of a
      prospective randomized study to compare placebo, growth hormone, oxandralone, and
      testosterone, singly and in combination, in promoting short-term growth
      acceleration and increased final height. The pretreatment cross-sectional
      correlation between bone ALP and height velocity was poor (P > or = 0.25), but
      was much higher (P = 0.0001) 3 months after treatment started. In each treatment
      group, there was a parallel relation between bone ALP and height velocity through
      time. Individual children showed a variety of growth responses over 12-42 months,
      but in almost all cases bone ALP paralleled height velocity. Within individual
      children, bone ALP was strongly correlated with 6-month height velocity (r > 0.9
      in 30% of the children, r > 0.7 in 70%). We conclude that bone ALP is a useful
      short-term marker of growth in short normal children treated with growth hormone.

PMID- 7729045
TI  - Immunoassay of a tartrate-resistant acid phosphatase in serum.
AB  - A tartrate-resistant acid phosphatase (TRACP) was purified from cord plasma by
      use of cation-exchange chromatography (carboxymethyl Sepharose), gel-filtration
      chromatography (Sephacryl S-200), and preparative isoelectric focusing. After
      raising polyclonal antibodies to the purified TRACP in rabbit, we used the
      antiserum to develop an ELISA. The antiserum cross-reacted with an extract of
      bone, but not with extracts of spleen, erythrocytes, platelets, or osteoblasts or
      with prostatic acid phosphatase. With this ELISA we determined the concentration
      of serum TRACP in healthy men to be 197 (61-301) micrograms/L (median and range).
      Serum TRACP concentrations were significantly higher in children and
      postmenopausal women and in patients with chronic renal failure,
      hyperparathyroidism, or hyperthyroidism. Estrogen replacement therapy of
      postmenopausal women for 3-6.5 months decreased their serum TRACP concentration
      by 70%.

PMID- 7729046
TI  - Validation of allele-specific polymerase chain reaction for DNA typing of HLA
      B27.
AB  - To find a specific method for HLA-B27 typing for the diagnosis of rheumatic
      disorders, we extensively tested the single-step B27-specific polymerase chain
      reaction (PCR) described by Dominguez et al. (Immunogenetics 1992;36:277-82).
      This method, which relies on specific primer recognition of a sequence in the
      third exon (unique to the B27-allele), was used for screening of 270
      characterized blood samples, 57 of which were B27-positive. The method proved to
      be both sensitive and specific: It unambiguously identified all B27-positive
      samples and produced no false-positive results. For approximately 1% of the
      samples, we had to repeat DNA isolation and PCR to obtain a clear control
      amplification signal. In contrast to the specificity of the PCR method, parallel
      performed flow cytometry gave ambiguous results in 3% of the samples because of
      antibody cross-reactivity. Flow cytometry and the PCR method described were
      similar in labor and costs. Therefore, we conclude that the proposed single-step
      PCR is feasible in a routine laboratory and would improve the reliability of HLA
      B27 typing.

PMID- 7729047
TI  - Detection of BCR-ABL transcripts from the Philadelphia translocation by
      hybridization in microtiter wells and time-resolved immunofluorometry.
AB  - Two hybridization assays have been developed to detect BCR-ABL mRNA transcripts
      arising from the Philadelphia translocation. Both assays use time-resolved
      immunofluorometric detection of polymerase chain reaction-amplified BCR-ABL mRNA
      sequences hybridized to specific probes. In configuration I, biotinylated
      amplified target is immobilized onto streptavidin-coated wells and hybridized to
      a probe labeled with the hapten digoxigenin. Hybrids are detected via an alkaline
      phosphatase-labeled antibody and fluorosalicylylphosphate as substrate. The
      fluorosalicylate produced forms highly fluorescent complexes with Tb(3+)-EDTA. In
      configuration II, biotinylated probe is immobilized onto streptavidin-coated
      wells. PCR, performed in the presence of hapten-labeled deoxyribonucleotide,
      generates labeled product, which is hybridized to immobilized probe and
      quantified as above. BCR-ABL transcripts from one leukemic cell amidst mRNA from
      500,000 normal granulocytes are detectable with signal/background ratios as high
      as 36.4 and 24.6 for configurations I and II, respectively. The respective CVs
      for the assays were 6.6-9.0% and 5.1-12.5%.

PMID- 7729048
TI  - Advances in genosensor research.
AB  - Microfabricated devices containing arrays of nucleic acid hybridization sites,
      known as genosensors, are being developed for a variety of uses in genomic
      analysis. A great deal of the overall genosensor development effort involves
      optimization of experimental conditions in the actual use of genosensors. Here we
      describe a "low-tech" form of genosensor technology, involving arrays of
      oligonucleotides on glass microscope slides, which can be used to define optimal
      operating conditions and to develop applications of hybridization arrays in
      genome mapping and sequencing. In addition, we describe a porous silicon
      genosensor, which can be operated in a flowthrough mode, and discuss its
      advantages over current flat-surface designs. Porous silicon genosensors
      containing arrays of DNA fragments offer several unique capabilities in genome
      analysis.

PMID- 7729049
TI  - Prevalence of serum antithyroid peroxidase antibodies in 85-year-old women and
      men.
AB  - Antithyroid peroxidase antibodies (TPOAb) were determined by competitive
      radioassay in serum samples obtained from a representative population of 85-year
      olds (601 women and 285 men). The prevalence of increased TPOAb concentration was
      significantly higher in the women. In individuals without previously known
      thyroid dysfunction, 16% of the women and 9% of the men had TPOAb concentration >
      100 kilo-units/L, the upper decision limit. We found a direct relationship
      between TPOAb and thyrotropin (TSH) concentrations and an inverse relationship
      between TPOAb and free thyroxine (T4) concentrations, but no relationship between
      TPOAb and defined disorders or treatment with pharmaceutical drugs. Exclusion of
      individuals with increased TPOAb concentration and conditions influencing TSH and
      free T4 concentrations resulted in a decrease of the upper reference limit for
      TSH concentration and an increase of the lower limit for free T4 concentration,
      indicating that high TPOAb concentration should be taken into account when
      evaluating normal reference intervals for thyroid-function tests in the elderly.

PMID- 7729050
TI  - Vitamin C and glycohemoglobin.
AB  - Three groups of 10 age- and sex-matched nondiabetic volunteers took 0, 750, or
      1500 mg of vitamin C each day for 12 weeks. Glycohemoglobin (GHb) was measured by
      HPLC, electrophoresis, affinity chromatography, and immunoassay at baseline (-4
      weeks and -1 day), during supplementation (6 weeks and 12 weeks), and after
      supplementation ended (6 and 12 weeks). Plasma vitamin C increased twofold during
      supplementation but, in contrast with the results of Davie et al. (Diabetes 1992;
      41:167-73), there were no between-group differences in GHb, glucose, and
      fructosamine concentrations. Fructosamine may have increased with storage time.
      The net effects of vitamin C on absolute GHb at 12 weeks vs -1 day (and at 12
      weeks vs 12 weeks after) in % GHb amounted to: HPLC -0.035 (-0.050);
      electrophoresis +0.005 (+0.035); affinity chromatography -0.070 (+0.015); and
      immunoassay -0.110 (+0.025). We conclude that supplementation of nondiabetics
      with 750 or 1500 mg of vitamin C daily for 12 weeks does not cause interference
      in GHb determinations by HPLC, electrophoresis, affinity chromatography, or
      immunoassay, and does not reduce in vivo Hb glycation.

PMID- 7729051
TI  - Direct measurement of high-density lipoprotein cholesterol in serum with
      polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin.
AB  - We have developed an automated method for measuring high-density lipoprotein
      (HDL)-cholesterol in serum without prior separation, using polyethylene glycol
      (PEG)-modified enzymes and sulfated alpha-cyclodextrin. When cholesterol esterase
      and cholesterol oxidase enzymes were modified with PEG, they showed selective
      catalytic activities towards lipoprotein fractions, with the reactivity
      increasing in the order: low-density lipoprotein < very-low-density lipoprotein
      approximately chylomicron < HDL. In the presence of magnesium ions, alpha
      cyclodextrin sulfate reduced the reactivity of cholesterol, especially in
      chylomicrons and very-low-density lipoprotein, without the need for precipitation
      of those lipoprotein fractions. The combination of PEG-modified enzymes with
      alpha-cyclodextrin sulfate provided selectivity for the determination of HDL
      cholesterol in serum in the presence of a small amount of dextran sulfate without
      the need for precipitation of lipoprotein aggregates. The results of the HDL
      cholesterol assayed in serum by this direct method correlated well with those
      obtained by precipitation-based methods and also that by an ultracentrifugation
      method.

PMID- 7729052
TI  - Testing the accuracy of total cholesterol assays in an external quality-control
      program. Effect of adding sucrose to lyophilized control sera compared with use
      of fresh or frozen sera.
AB  - We studied the suitability of various types of human serum preparations to test
      the accuracy of total cholesterol measurements in the External Quality Assessment
      scheme in The Netherlands, in which approximately 180 laboratories participate.
      Checked against the certified Abell/Kendall Reference Method, large reagent
      dependent negative biases were observed with lyophilized serum that was
      insufficiently cryoprotected. The biases for the reagents of Du Pont, Roche, and
      Beckman averaged -16.7%, -9.2%, and -7.6% respectively; the least bias, -0.4%,
      was obtained with reagent from Boehringer Mannheim. The beneficial effect of
      cryoprotection with sucrose was demonstrated by the decrease in interreagent
      variation from 5.4% to 1.9%, the latter value being comparable with the values
      for fresh and once-frozen pooled serum (1.3% and 1.7%, respectively). We conclude
      that the detrimental effect of lyophilization on serum matrix can be minimized by
      suitable cryoprotection with 200 g/L sucrose.

PMID- 7729053
TI  - Quantification of orotic acid in dried filter-paper urine samples by stable
      isotope dilution.
AB  - A rapid, sensitive, and specific method for quantification of orotic acid from
      dried filter-paper urine samples is described. The method involves stable isotope
      dilution with 1,3-[15N2]orotic acid analysis by gas chromatography-mass
      spectrometry. The assay is sufficiently sensitive to be used with solvent
      extraction techniques commonly used for urinary organic acid analysis. Extraction
      efficiencies of both native and isotopic orotic acid from dried filter paper and
      from water were 31% and 28%, respectively. The concentration of orotic acid in
      dried filter-paper urine specimens from 50 healthy controls was 1.1 +/- 0.67
      (mean +/- SD) mmol/mol of urinary creatinine. The same 50 urine samples, analyzed
      directly from a 5-mL aliquot of liquid urine, gave values of 0.93 +/- 0.51. The
      correlation coefficient between the results obtained by the two different
      collection methods was 0.87. Age-related reference values in filter-paper samples
      are also reported. The concentrations, which are normalized to urinary
      creatinine, decrease with age. This method is applicable to rapid screening for
      urea cycle disorders and may also be used for carrier testing of ornithine
      transcarbamylase deficiency.

PMID- 7729054
TI  - Standardized method for high-resolution 1H-NMR of cerebrospinal fluid.
AB  - This study describes a standardized method for recording single-pulse 1H-nuclear
      magnetic resonance (1H-NMR) spectra from cerebrospinal fluid (CSF). Quantitative
      data for alanine, valine, threonine, and lactic acid correlated well with data
      obtained with conventional techniques. The pH of the samples is important for the
      reproducibility of the chemical shift of resonances, and should be standardized
      to improve recognition and assignment of resonances. A database of resonances
      from various metabolites is presented. Fifty compounds could be identified in
      CSF, 15 of which had not been observed earlier in NMR studies of CSF. We describe
      for the first time in the literature, to our knowledge, 3-hydroxyisovaleric acid
      as a regular component of many CSF samples. As examples of the diagnostic power
      of the technique, spectra are shown of CSF from patients with three different
      inborn errors of metabolism. We found high concentrations of N-acetylaspartic
      acid, citric acid, and succinic acid in CSF from a patient with Canavan disease.
      This is indirect evidence for the existence of a carrier mechanism that is shared
      by these di- and tricarboxylic acids.

PMID- 7729055
TI  - Rapid gas-chromatographic assay of lactulose and mannitol for estimating
      intestinal permeability.
AB  - We developed a gas-chromatographic method to determine urinary mannitol and
      lactulose. The procedure for purification of urine by a resin was optimized for
      purification of analytes and high recovery; the aliquot of resin chosen (500 mg)
      was kept in contact with the urine for 1 min. The recoveries of mannitol and
      lactulose were > 85% at concentrations that include both normal and pathological
      values. Sugars were converted to oximes before the silylation step to avoid
      multiple peaks for the anomeric forms. The calibration was linear over the range
      0.1-1 microgram of sugar injected. Analytical recovery of the sugars ranged from
      90% to 95.3% for mannitol and from 90.4% to 95.8% for lactulose. The mean within
      day imprecision (CV) was 6.2% for mannitol and 4.7% for lactulose; the between
      day CV was 6.7% for mannitol and 5.1% for lactulose. A lactulose/mannitol ratio
      of 0.035 completely differentiated 28 normal children and 28 children with active
      gluten-sensitive enteropathy, whose mean ratios were 0.022 (SD 0.007) and 0.084
      (SD 0.054), respectively.

PMID- 7729056
TI  - Determination of homocysteine by HPLC with pulsed integrated amperometry.

PMID- 7729057
TI  - Homocysteine in plasma: stabilization of blood samples with fluoride.

PMID- 7729058
TI  - Increased PO2 measured in a patient with type II cryoglobulinemia.

PMID- 7729059
TI  - Friedewald formula.

PMID- 7729060
TI  - Interlaboratory testing scheme designed as a clinical chemistry control
      procedure.

PMID- 7729061
TI  - Lack of relationship between actual ionized calcium and pH in umbilical cord
      blood.

PMID- 7729062
TI  - Alkaline azobilirubin color reaction to determine sodium azide.

PMID- 7729063
TI  - Optimal bin widths for frequency histograms and ROC curves.

PMID- 7729064
TI  - D-lactic acidosis in patients with short bowel syndrome.

PMID- 7729065
TI  - Snack crackers yield opiate-positive urine.

PMID- 7729066
TI  - Measuring outcomes: why now?
AB  - Intense scrutiny of the American healthcare paradigm will alter the activities of
      patients, providers, and payors. Government reform and marketplace-driven managed
      care programs create uncertainty. Quality, access, and cost concerns also drive
      change. Quality is conformity to requirements, and specification of requirements
      creates policy debate. Variability in utilization creates an accountability chasm
      between payors and providers that cannot be bridged without understanding the
      uncertainties in "appropriateness" research. Quality and access appear secondary
      to cost. Cost discussions must differentiate cost and charge. Inappropriate
      charge benefit analyses may temporarily benefit a specific organization but are
      unlikely to create long-term societal benefit. Multiple transitions have begun,
      including a shift from disease care to healthcare, provider mentality to consumer
      mentality, and provider autonomy to collaboration and accountability.
      Laboratories will be expected to provide outcomes, not tests; income will be
      related to covered lives, not volume, and profit will shift from "piecework and
      efficiency profit" to "prevention profit." Only good "outcomes" measurement can
      reduce uncertainty. The laboratory contribution to value in care processes
      remains unclear. What information is added by each result? How can results help
      prevent the need for future services? These are our challenges.

PMID- 7729067
TI  - Diagnostic information as a commodity.
AB  - In estimating the cost-effectiveness of diagnostic procedures, it is helpful to
      treat diagnostic information as a commodity with a unit price. The amount of
      useful information provided by a test result can be measured in binary units
      (bits), and the unit price of the information produced by the test result can be
      expressed in dollars per bit in much the same way that the price of gold is given
      in dollars per ounce. This allows comparison of the unit prices of various
      diagnostic tests, examination of the effect of multiple testing, and calculation
      of the most cost-effective conditions for screening tests.

PMID- 7729068
TI  - Diagnosis of human heritable diseases--laboratory approaches and outcomes.
AB  - Detection of mutant human genes is rapidly becoming an integral part of clinical
      practice. Human disease may arise by genetic deletion, insertion, fusion, point
      mutation, or amplification of unstable sequences. Such changes in structure may
      occur in germ cells or somatically. Rapid advances in understanding the complex
      nuclear and mitochondrial genomes necessitates deployment of a variety of methods
      to identify aberrant genes. These techniques include polymerase chain reaction,
      Southern transfer, and allele-specific hybridization studies, as well as methods
      to unmask mismatches between mutant and normal sequences. Development of protein
      truncation tests has added a vehicle for assessing larger DNA segments for
      mutations that cause premature translational termination. Linkage analysis
      remains an important tool where direct assay of disease-causing mutations is not
      possible. Considerations of confidentiality, informed consent, and insurability
      are important whenever genetic testing is used. These issues will assume
      increasing importance as presymptomatic testing for heritable predispositions
      emerges for common conditions.

PMID- 7729069
TI  - Conducting outcomes research: past experience and future directions.
AB  - The Centers for Disease Control and Prevention (CDC) was delegated authority to
      conduct the studies mandated in the Clinical Laboratory Improvement Amendments of
      1988 (CLIA). Since that time, the CDC has been planning and implementing a
      research program, Evaluation of Quality of Laboratory Practices and Standards
      (EQLPS), aimed at demonstrating a clear linkage between patient outcome and
      laboratory practices and standards such as proficiency testing, quality
      assurance, and personnel standards. The goal of EQLPS is to improve the quality
      of laboratory medicine by providing a scientific and technical basis for
      laboratory practices and standards. In October 1995, the CDC will sponsor an
      Institute entitled "Frontiers in Laboratory Practice Research," during which
      strategies for conducting laboratory practice research will be discussed. The
      Institute should help identify research strategies that will eventually provide
      the information necessary to develop appropriate practice guidelines for
      laboratory medicine.

PMID- 7729070
TI  - For goodness' sake: expected therapeutic benefit as a basis for healthcare
      delivery.
AB  - The current debate on our healthcare system has focused primarily on the cost of
      care. Because of drastically rising costs and their burden on our economy,
      government and the private sector have developed many approaches to reduce these
      costs. Managed care, special contracting arrangements, and government fiat have
      all been used to stem the tide of rising costs--with variable success. We propose
      that the primary goal of healthcare is the provision of patient benefit, and we
      describe a model that calculates an expected benefit in terms of survival and
      quality of life. We have applied this model to a cohort of patients undergoing
      coronary angiography to determine the distributions of benefit. Furthermore, we
      describe a reimbursement strategy that relates the expected therapeutic benefit
      to the reimbursement received for that therapy--the greater the benefit, the
      greater the reimbursement. The future of our healthcare system lies in keeping
      the patient at the center of the debate on the delicate balance between optimal
      care and societal cost.

PMID- 7729071
TI  - Financial viability of screening for drugs of abuse.
AB  - Urine drug testing is now a common practice in the American workplace; a recent
      survey indicated that > 90% of companies with > 5000 employees have some type of
      testing program. These programs have indeed reduced the rate of drug-positive
      test results; for example, recent data from the Federal Aviation Agency show that
      the rate for 1993 was 0.82% compared with 0.95% for 1992. Many corporations have
      stated that urine drug testing, as a component of a substance abuse policy,
      results in significant savings, e.g., from decreased absenteeism and turnover.
      The United States Postal Service recently completed a longitudinal study on the
      economic benefits and found that, over the average tenure of an annual intake of
      employees, there were savings of more than $100 million. Although this study
      clearly demonstrates the financial benefits of preemployment drug testing, the
      decision to test is not based solely on this but also on the regulatory
      environment and on the potential impact of a major accident attributable to the
      use of drugs or alcohol in the workplace.

PMID- 7729072
TI  - Establishing a direct laboratory access program.
AB  - Direct Laboratory Access (DLA) refers to a program whereby individuals who wish
      to have laboratory testing performed can avail themselves of such testing
      independently of a physician referral. DLA benefits both physicians and
      consumers. Physicians benefit by not having to invest time and office resources
      for consumers who do not seek medical intervention but rather who visit
      physicians for the sole purpose of obtaining permission to have laboratory tests
      performed. Consumers benefit by avoiding physician encounters they do not want,
      by receiving state-of-the-art laboratory testing they do want, and by avoiding
      the added expense and inconvenience of a physician office visit. DLA appeals to
      an anxious, educated, and somewhat affluent niche market. The program fills a
      void in the provision of health services while providing a small stream of
      revenue for laboratories.

PMID- 7729073
TI  - Dementia with ALS features and diffuse Pick body-like inclusions (atypical Pick's
      disease?).
AB  - An autopsy case of dementia beginning with right hand muscle atrophy was
      reported. A 42-year-old woman with no family history of neurologic disease
      developed weakness of the right hand at age 30, and was diagnosed as having
      amyotrophic lateral sclerosis (ALS). The weakness and atrophy spread to the four
      extremities subsequently. At age 36, she could not walk without assistance. At
      age 38, she was first noted as having dementia with forced crying, and she also
      showed generalized muscle weakness and atrophy. She rapidly developed akinetic
      mutism, and died of respiratory failure at age 42, 12 years after the onset of
      the symptoms. Macroscopically, the brain showed fronto-temporal atrophy.
      Microscopic examination revealed numerous intracytoplasmic inclusions throughout
      the central nervous system (CNS) including anterior horn of the spinal cord. The
      inclusions were stained moderate to dark brown with silver stain. Electron
      microscopically, they consisted of fibrils covered along most of the length with
      granular and fuzzy materials. This case was thought to be difficult to categorize
      in any known neuro-degenerative diseases. We proposed the case to be "atypical
      Pick's disease" with ALS features. This case might be a new entity of neuro
      degenerative disease.

PMID- 7729074
TI  - Gliomatosis cerebri: report of an atypical case.
AB  - Gliomatosis cerebri (GC) is a rare, diffusely infiltrating tumor of
      neuroepithelial origin. The clinical diagnosis is difficult since GC is a diffuse
      and progressive disease of the central nervous system (CNS). Non-specific
      findings can be detected by computed tomography (CT) whereas, according to some
      authors, the extent of this tumor can be accurately depicted by magnetic
      resonance imaging (MRI). In this paper the neuroradiologic, neuropathologic and
      immunohistochemical features in a further case of GC are reported.

PMID- 7729075
TI  - Hemangiopericytoma of the cerebello-pontine angle. Diagnostic pitfalls and the
      diagnostic value of the subunit A of factor XIII as a tumor marker.
AB  - The authors report on a case that during its 9-year-long history has repeatedly
      been misdiagnosed due to the misleading clinical and histopathological findings.
      The patient has been treated, in chronological order, for cerebrovascular
      disease, acoustic Schwannoma, glomus tympanicum tumor (chemodectoma) and finally
      turned out to have an intracranial hemangiopericytoma that originated from the
      area of the glomus tympanicum and eventually widely metastatized within and
      outside the intracranial compartment. The proper diagnosis was reached with the
      help of detailed immunohistochemical analysis. The subunit A of Factor XIII
      (FXIIIa) can be demonstrated on formaldehyde-fixed paraffin embedded sections. It
      has recently been shown that FXIIIa reactivity is characteristic and hence
      diagnostic of a subpopulation of cells within systemic and intracranial (central)
      hemangiopericytomas (HPCs). Since it is consistently missing from all cell
      components of ordinary meningiomas, glomus tumors (chemodectomas) and a host of
      other soft tissue tumors, its presence or absence is a helpful sign in various
      differential diagnostic dilemmas.

PMID- 7729076
TI  - Immunohistological study of a case of cerebral Langerhans cell histiocytosis in
      brain biopsy.
AB  - Although several attempts at the immunohistochemical characterization of
      histiocytosis have recently been made there is only one paper which reports a
      case of cerebral Langerhans cell histiocytosis (LCH) diagnosed by biopsy. This
      paper presents a bioptically diagnosed case of juvenile histiocytosis. The panel
      of antibodies used was as follows: anti-S-100, 2 different antibodies to anti
      interleukin 2, anti-lysozyme, anti-LEU M1, anti-MAC 387, anti-major
      histocompatibility complex II and anti-GFAP. Microglia markers--Griffonia
      simplicifolia and RCA 1 lectins were also utilized. The proliferating cells
      produced a positive response to S-100, lysozyme and a partially positive response
      to HLA DR, but responded negatively to MAC 387, LEU M1, lectins, IL2R and GFAP.
      Our results were compared and analyzed in the light of those obtained by other
      authors.

PMID- 7729077
TI  - Primary balloon cell malignant melanoma of the right temporo-parietal region
      arising from meningeal naevus.
AB  - An unusual case of primary balloon cell malignant melanoma (BCMM) in brain
      arising from melanoblastic meningeal (or diffuse meningeal) naevus in a 30-year
      old woman has been presented. The characteristic balloon cells were amelanotic or
      focally extremely weakly melanotic. The large, uniformly looking, tightly packed,
      pale "balloon cells" formed the homomorphic texture of the spherical well
      demarcated tumor lying in the white matter of right temporo-parietal region
      beneath the nevoid-looking partially melanotic diffuse meningeal and cortical
      infiltrate. Positive melanoma antigen HMB-45, S-100 protein and vimentin along
      with negative epithelial membrane antigen EMA and markers for macrophages like
      alfa-1-antitrypsine and CD-68 proved that balloon cells belong to and may form a
      peculiar type of melanoma. The lack of suspected skin or mucosal naevi and
      coexisting meningeal naevus speak for the primary character of the balloon cell
      melanoma. According to our knowledge it is the first primary balloon cell
      melanoma of the brain. Differential diagnosis and the pathogenesis are discussed.

PMID- 7729078
TI  - Immunoreactive antigenic sites of Cysticercus cellulosae relevant to human
      neurocysticercosis--immunocytochemical localization using human CSF as source of
      antibody.
AB  - With a view to identify the relevant antigens of Cysticercus cellulosae,
      recognized within human central nervous system, immunocytochemical localization
      of antigens on the cestode larva has been carried out using cerebrospinal fluid
      of patients as the source of primary antibody. CSF from nine proven cases of
      neurocysticercosis, two cases of culture proven tuberculous meningitis and two
      cases of spinal disc prolapse with no other infective or neurological disorder
      were used in this study. The CSF from all the cases of neurocysticercosis
      intensely reacted with the glycocalyx over the integument of the cyst bladder
      wall. The other structures recognised by the CSF antibodies were cytoplasm of the
      tegumentary cytons, stroma and the ductular system of the bladder wall. The
      cells, stroma and calcareous corpuscles of the scolex reacted variably with the
      CSF. Tegument of the spiral canal and sucker muscles in the scolex were not
      immunoreactive. We strongly suggest that the glycocalyx is the most antigenic
      anatomical structure of the Cysticercus cellulosae and the patients develop
      antibodies to it.

PMID- 7729079
TI  - Liposarcoma with unusual neurological manifestations.
AB  - Central nervous system involvement in liposarcoma is rare, the only symptom
      reported in the literature being local compression of the spinal cord. An
      exceptional case with peripheral nerve involvement due to local recurrence, in
      addition to spinal cord compression and cavernous sinus syndrome due to
      metastases is reported.

PMID- 7729080
TI  - Selective necrosis of the posterior pituitary gland--case report.
AB  - A 78-year-old man had extensive necrosis of the posterior lobe of the pituitary
      at autopsy. The anterior lobe was normal. This pattern of damage to the posterior
      lobe has not been described to date.

PMID- 7729081
TI  - Herpes simplex virus brainstem encephalitis in an AIDS patient.
AB  - We report a case of a virulent, atypical herpes simplex infection in the
      brainstem of a patient with Acquired Immune Deficiency Syndrome (AIDS) which was
      characterized by demyelination and oligodendroglial tropism. At autopsy the
      brainstem showed demyelination. Immunocytochemistry, in situ hybridization, and
      electron microscopy confirmed the presence of herpes simplex virus (HSV). Viral
      cultures demonstrated HSV type 1. Neuroinvasiveness and neurovirulence were
      studied by intraperitoneal inoculation of susceptible mouse strains (A/J and
      Balb/cByJ) with different viral titers. The LD50 of the clinical isolate was 5
      orders of magnitude greater than the LD50 of a laboratory HSV strain (HSV type 1
      KOS). The brains of the mice inoculated with the clinical isolate showed
      brainstem and cerebellar demyelination.

PMID- 7729082
TI  - Cerebral toxoplasmosis in a patient with the acquired immunodeficiency syndrome
      presenting as obstructive hydrocephalus.
AB  - We report the case of an adult AIDS-patient with an unusual pattern of
      toxoplasmic encephalitis resembling the congenital form of the disease. Extensive
      exudative ependymitis and plexitis caused obstruction of internal CSF-pathways
      with rapid development of hydrocephalus. CT showed hydrocephalus and multifocal
      hypodense non-enhancing lesions. Direct microscopy of the CSF demonstrated
      Toxoplasma organisms.

PMID- 7729083
TI  - Location of nucleolar organizer regions (AgNORs) in the nuclei of astrocytic
      tumors.
AB  - Seventy-nine astrocytic tumors classified according to the WHO classification and
      stained with a modified AgNOR staining technique were analyzed with the help of
      an automatic image analyzing system. With increasing malignancy there is an
      increase of AgNORs per cell. Furthermore, AgNORs move from a more central to a
      more peripheral position within the nucleus, thus leading to a significant
      increase of the AgNOR count at the periphery of the nucleus. An inverse relation
      was found at the center. With regard to AgNORs, there are little differences
      between anaplastic astrocytomas and small cell glioblastomas. The most striking
      differences were seen between differentiated (grade 2) and anaplastic (grade 3)
      astrocytomas.

PMID- 7729084
TI  - Rasmussen's syndrome: a study of potential viral etiology.
AB  - Rasmussen's syndrome (RS) is a devastating constellation of severe, unilateral
      focal motor epilepsy resistant to anticonvulsant therapy, followed by ipsilateral
      neurological deficits and neuropathological evidence of a chronic encephalitis
      occurring primarily in the pediatric population. Recent reports have identified
      viral genomic material for cytomegalovirus (CMV) and Epstein-Barr virus (EBV)
      using in situ hybridization (ISH) in brain tissue of RS patients. We studied 10
      biopsy- and resection-specimens from seven patients using biotinylated double
      stranded DNA probes to CMV, herpes simplex virus (HSV) and EBV to confirm these
      results. Two patient samples were also evaluated by electron microscopy and one
      using standard immunoperoxidase techniques. We were unable to identify any
      evidence of viral material utilizing one of these techniques. There was some
      nonspecific localization of crystalline material by in situ hybridization over
      nuclei, which may account for literature reports of positivity, although one
      cannot be sure since photomicrographs were not included in these reports.
      Although the neuropathological morphology of the identifiable lesions in resected
      specimens is consistent with that seen in other viral encephalitides, our
      findings fail to support the role of CMV, HSV, or EBV as the etiology and sole
      factor in the development of Rasmussen's syndrome.

PMID- 7729085
TI  - [Non-herpetic acute limbic encephalitis].
AB  - We reported four cases of acute encephalitis, in which MRI abnormalities
      localized in the limbic system. In the four cases, fever and consciousness
      disturbance were commonly found and convulsive seizures appeared in three. Within
      10 days, their consciousness level became clear, but severe amnestic syndrome
      remained as sequela. Cerebrospinal fluid (CSF) at the acute stage revealed mild
      lymphocytic pleocytosis and elevated protein. MRI revealed abnormal signal
      intensities in both hippocampi and amygdaloid bodies, although CT scans were
      normal. Herpes simplex encephalitis selectively affects one or both temporal
      lobes and the limbic system, But our cases spared the temporal lobes.
      Additionally, serum and CSF antibody titers by CF and ELISA for herpes simplex
      virus (HSV) were within normal range from the acute to convalescent stages.
      Neither HSV type 1 and 2 DNA genomes by sensitive PCR-hybridization method were
      detected in CSF taken from the acute stage of all four cases. On the other hand,
      paraneoplastic limbic encephalitis is known as a subacute encephalitis
      predominantly involving the limbic system. MRI shows high signal intensities on
      T2-weighted in both medial temporal lobes. In our cases, this type of limbic
      encephalitis was excluded because of the acute onset and lack of malignancy.
      Accordingly, our four cases are regarded as non-herpetic acute limbic
      encephalitis. Several Japanese similar cases have been reported. Further
      etiological studies should be performed.

PMID- 7729086
TI  - [Chiromegaly in syringomyelia--radiologic studies of hand bones].
AB  - Chiromegaly, localized hypertrophy of a hand, is known to be a rare but
      pathognomonic trophic disturbance in syringomyelia. We recently reported that the
      sympathetic hyperfunction was associated with chiromegaly. This time we carried
      out radiological studies of hand bones in 4 patients with syringomyelic
      chiromegaly. In simple roentogenography, enlargement and enhanced shadows of hand
      bones were recognized in the chiromegalic side. Radiographic measurements showed
      metacarpophalangeal length and width were increased by 1.7% and 8.8% respectively
      compared to the normal side, and metacarpal index was decreased significantly in
      the chiromegalic side. In X-ray photodensitometry (MD/MS method) of the second
      metacarpal bones, bone density was increased by 10.6% compared to the normal
      side. These results suggested that bone hypertrophy was associated with
      chiromegaly in patient with syringomyelia. Trophic disturbance may exert some
      influence on the bone tissue.

PMID- 7729087
TI  - [Preferentially affected sites of cerebral arteriosclerosis in vascular dementia
      of Binswanger type--a study of MRI and MR angiography].
AB  - MRI and MR angiography (MRA) were analyzed to evaluate the preferential sites of
      cerebral arteriosclerosis in 129 normal controls and 27 patients with vascular
      dementia of Binswanger type (BVD; mean age 75.0 years). Small vessel disease,
      indicated as advanced high intensity areas on T2-weighted MRI, increased with
      advancing age, while large vessel sclerosis detected with MRA did not increase
      after the age of 80 years. Large vessel sclerosis was not always accompanied with
      advanced high intensity areas. Large vessel sclerosis was found in 12 (44.4%) of
      27 patients with BVD, and was as common as that of the controls of the eighth
      decade. Large vessel sclerosis was frequently seen in the cases suffering from
      BVD below 70 years of age or with hypertension. In conclusion, patients with BVD
      develop cerebral arteriosclerosis more preferentially in the small vessels rather
      than the large vessels especially in aged cases, of which incidence is similar to
      that of the normal controls over 80 years of age.

PMID- 7729088
TI  - [The effects of dopamine on regional cerebral blood flow in patients with
      Parkinson's disease before and after L-dopa--measurement by Xe-enhanced CT].
AB  - Regional cerebral blood flow (rCBF) was measured using the stable xenon enhanced
      CT method in previously untreated 13 patients with Parkinson's disease to
      evaluate CBF abnormality related to dysfunction of the nigrostriatal dopaminergic
      neurons. The patients comprised 5 men, 8 women with Hoehn-Yahr stage II-III. Age
      at onset ranged from 51 to 73 years (mean +/- SD, 61.8 +/- 8.9) and the duration
      of illness ranged from 1 to 96 months (15.1 +/- 24.1 months). In this series,
      there was no clinical evidence of hypertension, diabetes mellitus and cognitive
      impairment. rCBF was measured during 4-5-minutes inhalation of 33% stable xenon
      gas-67% oxygen. The first measurement of rCBF was performed in all of the
      patients before L-dopa treatment. After initiation of L-dopa treatment (333.3 +/-
      47.1 mg/day), the second measurement was carried out in 6 patients (1 man and 5
      women) who had shown symptomatic improvement. The interval between both
      measurements was 57.7 +/- 16.9 days. The following results were obtained. 1) No
      significant CBF asymmetry was noted in any of the striatum, pallidum, thalamus,
      cerebrum, cerebellum and frontal lobe in untreated patients with Parkinson's
      disease. 2) After L-dopa treatment, rCBF was significantly increased only in the
      striatum as compared with the pretreatment level (51.9 +/- 9.3-->63.1 +/- 9.9
      ml/100 g/min, p < 0.01). 3) This increase was significantly greater on the more
      severely affected side (contralateral to the predominantly symptomatic limb) (p <
      0.05). These results suggest that the increase of rCBF in the striatum is closely
      related to functional improvement of the nigrostriatal dopaminergic neurons.

PMID- 7729089
TI  - [Postural sway in patients with hereditary ataxia].
AB  - Instability of erect stance in patients with autosomal dominant hereditary ataxia
      was investigated by posturography. Postural sway on a force-measuring platform
      was measured quantitatively and sway frequencies were analyzed. Thirty patients
      from 27 families (15 men and 15 women, mean age of 53.1 years (SD 11.1)) were
      divided into two clinical groups. Twelve patients (group A) had "pure" cerebellar
      signs with no somatosensory afferent symptoms. Eighteen patients (group B) had
      sensory disturbances or diminished reflexes of the lower limbs, and a delayed
      latency of scalp P37 in somatosensory evoked potentials subsequent to tibial
      nerve stimulation. Postural sway of the patients of both groups was larger than
      that of normal subjects. Group A patients had a high antero-posterior/lateral
      sway ratio. Group B patients had increased sway with eyes closed. With respect to
      sway frequencies, group A patients had a power spectrum peak around 3 Hz. Group B
      patients had a power spectrum peak around 1 Hz, and twelve of them had another 3
      Hz component. Atrophy of the anterior lobe of the cerebellum shown by MRI was
      more prominent in patients who had the 3 Hz power spectrum peak than in patients
      lacking the 3 Hz peak. Quantitative posturography was useful to detect
      disturbances of the anterior lobe of the cerebellum and the spinal ascending
      system in patients with autosomal dominant hereditary ataxia.

PMID- 7729090
TI  - [Excitability of cervical lower motoneuron in juvenile muscular atrophy of the
      distal upper limb].
AB  - We investigated excitability of cervical lower motoneurons in 18 patients with
      juvenile muscular atrophy of the distal upper limb (Hirayama's disease), by F
      wave analysis and electrophysiological estimation of the number of motor units in
      the abductor pollicis brevis muscles of the affected side. In all the 18
      patients, F wave persistencies and numbers of motor units were decreased, whereas
      amplitudes of single motor unit potentials were increased, compared to those of
      age-matched normal controls. Patients in a progressive phase showed markedly
      decreased F wave persistencies, overwhelming the degree of decreases in numbers
      of motor units. In half of them, F waves were significantly increased in number
      during neck flexion. On the other hand, patients treated with neck brace and
      patients having stabilized symptoms with longer duration showed F wave
      persistence reduction corresponded to the degree of the motor unit loss, and no
      changes in F wave persistencies in a posture of neck flexion. These results
      suggest that the disorder is characterized by decreased excitabilities of
      survived cervical anterior horn cells, as well as denervation and reinnervation,
      presumably resulting from local compression or circulatory failure by anterior
      shift of the posterior dural wall during neck flexion.

PMID- 7729091
TI  - [MRI findings of posterior spinal artery syndrome--report of a case].
AB  - A 58-year-old woman presented with sudden onset of numbness and weakness of the
      lower limbs. She showed paraparesis associated with hyperreflexia and
      pathological reflexes in lower limbs. She showed decreased sensation of vibration
      and proprioception in lower limbs, as well as tingling sensation below Th11
      level. Pinprick and thermal sensations were spared. Magnetic resonance imaging
      (MRI) of the spinal cord revealed a symmetric high signal intensity area at the
      posterior medial part of the spinal cord spanning Th9 to Th11 on T2-weighted and
      proton density images. On the basis of clinical findings as well as MRI findings,
      we made a diagnosis of posterior spinal artery syndrome. The MRI findings are
      considered to be highly useful for the diagnosis of PSAS.

PMID- 7729092
TI  - [A case of post-rubella Guillain-Barre syndrome associated with ulcerative
      colitis].
AB  - A 56-year-old female with post-rubella Guillain-Barre syndrome (GBS) associated
      with ulcerative colitis (UC) was described. The patient dramatically recovered
      with plasmapheresis. It is very rare to encounter the neurological complication
      following rubella, especially polyradiculoneuropathy as observed in the present
      case. Significantly high titer of anti rubella antibody at admission and
      subsequent decrease in the titer suggest that rubella infection is likely to
      involve the development of GBS. Although GBS and UC are currently regarded as
      autoimmune disorders, association of GBS and UC is extremely rare and only a few
      cases have been reported. All of them including the present case developed GBS
      while UC was in remission. Similarly to previous reports of GBS or UC, our case
      also had an HLA type of B35 and DR2. Thus the present data suggest that
      infectious agents as well as individual susceptibilities are important for the
      development of GBS.

PMID- 7729093
TI  - [MRI of anterior spinal artery syndrome--chronological study].
AB  - We reported two cases of anterior spinal artery syndrome serially observed by MRI
      of the spinal cord. On the 8th and 10th days respectively, MRI with Gd revealed
      high signal intensity areas which were thought to be located in the anterior horn
      region of the two patients. On the 28th and 37th days respectively, there was no
      enhancement on the MRI with Gd. This enhancement in the anterior horn region
      might be correlated with vulnerability of the anterior horn to ischemia, and
      capillary proliferation due to simultaneous appearance of this enhancement with
      that of capillary proliferation after liquidization of the anterior horn.
      Therefore, the enhancement on the MRI indicates a correspondence with
      pathological findings and is be characteristic of anterior spinal artery
      syndrome.

PMID- 7729094
TI  - [A case of central pontine myelinolysis and extrapontine myelinolysis during
      rapid correction of hypernatremia].
AB  - A 69-year-old woman was admitted because of severe dehydration due to anorexia.
      Consciousness disturbance was found to be due to severe abnormalities of serum
      electrolyte balance, but recovered quickly by correcting the hyperosmolality.
      While the initial serum sodium value of 186 mEq/L was corrected to 139 mEq/L in 5
      days, locked-in syndrome, bilateral hand tremor and tetraparesis appeared. Brain
      magnetic resonance imaging (MRI) revealed symmetrically high signal intensity
      areas on T2-weighted images and low signal intensity areas on T1-weighted images
      in central part of pons and bilateral middle cerebellar peduncles. One and a half
      month later, these neurologic symptoms were improved and the MRI abnormalities
      also disappeared. Auditory brain stem responses which showed prolongations of III
      to V wave peak to peak latency at the onset returned to normal. It is noted in
      this case that central pontine myelinolysis (CPM) and extrapontine myelipolysis
      (EPM) appeared during the period of rapid correction of hypernatremia. Although
      it is known CPM and EPM are caused by hypernatremia or the rapid correction of
      hyponatremia, there has been reported only one case of CPM and EPM after rapid
      correction of hypernatremia. According to the hypothesis of Norenberg, rapid rise
      in serum sodium may cause CPM and EPM, but if CPM and EPM are caused by the rapid
      correction of hypernatremia in this case, CPM and EPM may be caused by another
      pathogenesis of the disorder.

PMID- 7729095
TI  - [A case of acute pandysautonomia and diffuse brain stem impairment associated
      with EB virus infection].
AB  - A 37-year-old woman with complaints of headache and nausea presented with
      temporary disturbance of consciousness, bulbar palsy and ataxic speech following
      flu-like symptoms. After the recovery of her consciousness, she developed
      orthostatic syncope and numbness all over the body. When she was admitted to our
      hospital two months later, she showed emaciation, diminished sweat production and
      butterfly-patch-like pigmentation. Neurologic examinations were remarkable for
      anisocoric pupils that sluggishly reacted to light, impaired left facial
      movements, bulbar palsy, numbness of the whole body, total loss of all tendon
      reflexes, incordination, ataxic gait and severe postural hypotension. Laboratory
      data included albuminocytogenic dissociation in cerebrospinal fluid, convergence
      nystagmus and dysmetria in electronystagmography, and right trigeminal paralysis
      in blink reflex. A sural nerve biopsy showed active axonal degeneration and
      severe loss of both myelinated and unmyelinated fibers. Examinations of autonomic
      nervous system disclosed diffuse impairment of sympathetic and parasympathetic
      postganglionic nerve. Based on these findings she was diagnosed as having acute
      pandysautonomia. High titer of serum EB virus antibody suggested that acute
      pandysautonomia and diffuse brainstem impairment may be related to EB virus
      infection.

PMID- 7729096
TI  - [Binswanger's type encephalopathy without alopecia and lumbago in young
      hypotensive patients].
AB  - Binswanger's type encephalopathy is characterized by progressive dementia and
      diffuse subcortical ischemic lesions associated with arteriosclerosis.
      Hypertension is believed to be a major pathogenic factor in causing this
      encephalopathy but there are some cases of the encephalopathy not suffering from
      hypertension. In 1985, Yamamura et al. and Fukutake et al. reported familial
      cases of normotensive juvenile Binswanger's type encephalopathy with alopecia and
      lumbago, and considered it to be possibly a new clinical syndrome. We reported
      three cases of relatively young-onset (under the age of 40) Binswanger's type
      encephalopathy with persistent hypotension. All three patients suffered from
      neither alopecia nor lumbago. Patient (male aged 40) had repeated episodes of
      ischemic stroke and had progressive dementia. Patients 2 (male aged 41) and 3
      (male aged 34) were not in a state of dementia, but had a history of transient
      ischemic attacks, and at present are completely symptom-free. Though there were
      no risk factors for cerebrovascular disease in these cases, the repeated episodes
      of ischemic stroke and the existence of small multiple lacunes in the basal
      ganglia on CT and MRI suggest that the white matter damage was principally due to
      a vascular disorder. In these cases, persistent hypotension was characteristic
      and might be a factor for the induction and exacerbation of this encephalopathy.
      These three cases are different from the classic form of Binswanger's type
      encephalopathy based on hypertension. Normotensive cases have been described
      before, but our cases do not seem to fall into this category because the blood
      pressure constantly remained hypotensive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729097
TI  - [Eosinophilic meningo-encephalo-myelitis due to Toxocara canis].
AB  - A 21-year-old woman was admitted to our hospital because of frontal headache, low
      grade fever and convulsion. The patient had long been in a close contact with a
      dog. Neurologic examination revealed meningeal irritation signs and cerebellar
      ataxia. Slight leukocytosis with an increased rate of eosinophils (23.2%) was
      present. A lumbar puncture yielded 330 leukocytes/microliters with 30% of
      eosinophils; protein, 55 mg/dl; and increased IgG synthesis, 43.6 mg/day. The
      antibody titer against Toxocara canis was positive both in serum and in CSF by
      the use of immunoblotting assay, Ouchterlony, indirect immunofluorescence and
      ELISA. Cranial MRI showed a number of lesions located mainly cortically or
      subcortically, which had a hyperintense appearance on T2-weighted images and were
      clearly enhanced with Gd-DTPA. A diagnosis of eosinophilic meningoencephalo
      myelitis due to Toxocara canis was made. In spite of the treatment with
      diethylcarbamazine and prednisolone, other lesions including cervical cord and
      optic nerves developed. Although CSF antibodies against Toxocara canis were
      reduced in titer, neurologic symptoms relapsed, raising the possibility that some
      allergic mechanisms may, at least in part, be responsible for this neurologic
      complication.

PMID- 7729098
TI  - [Clinical analysis of benign transient shuddering-like involuntary movement in
      elderly people].
AB  - We described 9 patients who developed acute onset benign transient shuddering
      like involuntary movement in elderly people. There was no consciousness
      disturbance or sensorimotor dysfunction. There were finger tremor, dysarthria, or
      gait disturbance in some patients. Asterixis was observed in the upper
      extremities in 2 patients. Duration of an involuntary movement was less than 1
      second, and the series of the involuntary movements continued for several days.
      This state appeared acutely and disappeared within 0.5 -4 days in the natural
      course without any sequelae. Oral administration of clonazepam was very effective
      to suppress this tremulousness. Seven of 9 patients developed recurrence.
      Although the cause of this syndrome remains unknown, we believe that this
      condition is clinically important for differential diagnosis of acute onset
      involuntary movements in elderly people.

PMID- 7729099
TI  - [A case of facioscapulohumeral muscular atrophy presenting unusual squatting
      gait, associated with tongue atrophy and sensorineural hearing loss].
AB  - A 16-year-old girl has presented speaking disturbance since early in life.
      Difficulty in running was noted at the age of 7. Her mother (46 years old) had
      moderate facial weakness and mild proximal weakness of the upper and lower limbs.
      Neurological examination at age 9 revealed bilateral facial weakness, tongue
      atrophy and weakness of the shoulder girdle, upper arms, and thighs. Deep tendon
      reflexes were absent in the four limbs. Gait was waddling. Over the next several
      years, she developed wasting and weakness around the shoulder girdle, upper arms,
      thighs, and increased lordosis. She lost the ability to walk by age 13. Since
      then, she has moved with difficulty in a squatting position. Serum CK was
      moderately increased and needle EMG in the extremities revealed myopathic
      changes. Muscle CT demonstrated marked atrophy of the proximal muscles in the
      left arm and lower limbs and mild atrophy of the calves. Audiogram showed
      bilateral mild sensorineural hearing loss. Muscle biopsy of the quadriceps at age
      9 showed nondiagnostic findings. This case could be diagnosed as congenital
      facioscapulohumeral muscular dystrophy. Tongue atrophy and sensorineural hearing
      loss are rarely associated with this syndrome, as well as unusual squatting gait.

PMID- 7729100
TI  - [A case with clinical features of progressive supranuclear palsy with apraxia-
      corticobasal degeneration?].
AB  - We report a 65-year-old female who have suffered from progressive gait
      disturbance for 3 years, followed by disorientation and forgetfulness.
      Neurological examination revealed dementia, constructional disability, limb
      kinetic apraxia, supranuclear gaze palsy, especially on downward gaze,
      symmetrical muscle rigidity and bradykinesia. Involuntary movements were
      undetectable. Brain MRI showed significant brain atrophy in the left fronto
      parietal lobe. The three-dimensional surface display with 131I-IMP demonstrated
      decreased cerebral blood flow in the left frontoparietal cortex. The diagnosis of
      this case is discussed with regard to either progressive supranuclear palsy or
      corticobasal degeneration or both.

PMID- 7729101
TI  - [Unilateral posterior spinal artery syndrome of the upper cervical cord
      associated with vertebral artery occlusion].
AB  - Upper cervical cord infarction in the territory of the posterior spinal artery is
      very rare. We present here an elderly man who developed right upper cervical (C1
      2) posterior spinal artery syndrome associated with vertebral artery occlusion. A
      62-year-old man suffered a right upper cervical (C1-2) posterior spinal artery
      syndrome. The onset was associated with neck flexion. Magnetic resonance imaging
      clearly showed an ischemic lesion. Cerebral angiography revealed occlusion of the
      distal end of an ipsilateral vertebral artery. The occlusion of the vertebral
      artery probably caused the cervical cord infarction. The neck flexion possibly
      induced thrombogenesis in the vertebral artery. Unilateral upper cervical
      posterior spinal artery syndrome associated with vertebral occlusion following
      neck flexion was suggested.

PMID- 7729102
TI  - [Sensory disturbance due to radiculopathy].

PMID- 7729103
TI  - [Migrating radiculopathy--an unusual complication of systemic lupus erythematosus
      in an HTLV-1 carrier].

PMID- 7729104
TI  - Neonatal jaundice--what now?

PMID- 7729105
TI  - Parvovirus B19-induced red blood cell aplasia complicating iron-deficiency
      anemia.

PMID- 7729106
TI  - Ganglioneuroblastoma masquerading as chronic vomiting.

PMID- 7729107
TI  - Confusion of innocent pressure injuries with inflicted dry contact burns.

PMID- 7729108
TI  - Isolated bicuspid aortic valve in a newborn with Down syndrome.

PMID- 7729109
TI  - Recommended childhood immunization schedule. United States--1995.

PMID- 7729110
TI  - Rickets secondary to phosphate depletion. A sequela of antacid use in infancy.
AB  - Two infants presented with growth failure and were found to have generalized
      osteomalacia (rickets) due to phosphate depletion from prolonged administration
      of an aluminum-containing antacid given for the symptoms of colic. One of the
      infants developed bilateral proptosis due to craniosynostosis related to the
      underlying metabolic bone disease. The chronic use of aluminum-containing
      antacids in infants has potential risk for the growing skeleton and is not
      innocuous. Therefore, antacid therapy should be used in low doses and very
      cautiously, with routine monitoring of serum calcium and phosphorus in children
      taking medications which reduce gastrointestinal phosphate absorption.

PMID- 7729111
TI  - Perinatal predictors of duration and cost of hospitalization for premature
      infants.
AB  - The duration and cost of intensive care for premature infants are important
      concerns for parents and health providers. We developed a mathematical model to
      predict length of stay and hospital charges from perinatal information. Length of
      stay was found to decrease exponentially with gestational age. The equation
      predicted the length of stay within 10 days in 86% of the cases and had an R2 =
      .765. Gestational age, the presence of respiratory distress syndrome, and
      pneumonia were the strongest predictors of hospital charges (R2 = .811). The
      gestational age threshold below which length and cost of hospitalization were
      significantly higher was 34 weeks.

PMID- 7729112
TI  - Cephalhematomas revisited. When should a diagnostic tap be performed?
AB  - The purpose of this article is to review the most appropriate method for
      investigating cephalhematomas for possible infection and to clarify the
      indications for diagnostic aspiration. MEDLINE searches were conducted for the
      period from 1972 to 1993, and all English-language reports were obtained. A
      summary of the findings from the reports identified was supplemented by a patient
      report. Eleven articles reporting 13 infected cephalhematomas were identified in
      the literature from 1972 to 1993. Escherichia coli was isolated from
      approximately 50% of the cephalhematomas that were aspirated. Most patients
      presented with obvious clinical signs of scalp infection, sepsis, meningitis,
      and/or osteomyelitis. Plain radiographs, bone scans, and enhanced CT scans were
      limited in their ability to determine if a cephalhematoma was infected unless
      associated osteomyelitis existed. Aspiration is the diagnostic procedure of
      choice for cephalhematomas suspected of being infected, as indicated by an
      increase in size, development of erythema, development of fluctuance, relapse of
      systemic infection, or a delay in the resolution of clinical symptoms of
      infection.

PMID- 7729113
TI  - Spinal cord injury in youth.
AB  - To identify special characteristics of the pediatric spinal cord-injured (SCI)
      population, we analyzed a database of 1,770 traumatic SCI patients; 88 (5%) fell
      into the two pediatric subgroups: 0-12 years (n = 26) and 13-15 years (n = 62) at
      time of injury. Differences between age groups were identified with regard to
      demographics, neurologic characteristics, associated injuries and complications,
      and management. Mode level of bony injury was C2 in preteens, C4 in teens, and C4
      C5 in adults. Scoliosis developed far more frequently in children, particularly
      preteens (23%), than in adults (5%). Violent etiologies, predominantly gunshots,
      accounted for a disproportionate share of injuries to preteens (19%) and African
      Americans (28%), as compared with adults (12%) and Caucasians (7%). This last
      finding underscores the urgent need to mount a response to the nationwide
      proliferation of gunshot-related SCI in children and minorities.

PMID- 7729114
TI  - Readability of pediatric patient education materials. Current perspectives on an
      old problem.
AB  - Written patient education materials are an important part of ambulatory pediatric
      practices. We evaluated the readability of 33 representative pediatric education
      materials using three common formulas: Fog, Fry, and SMOG. The majority of
      pamphlets had readabilities of grade nine or above. The need to use multiple
      readability formulas was also demonstrated. Although the three readability
      formulas were highly correlated, they were significantly different from each
      other when using a repeated measures analysis of variance (ANOVA) design. In
      almost half, the readability estimates differed by at least two grade levels. In
      addition, a large intrapamphlet variability for some pamphlets suggests a need to
      focus more attention on the readability of multiple sections within a pamphlet,
      not only on the overall or average readability. We conclude that the readability
      levels of patient education materials continue to be too high.

PMID- 7729115
TI  - Interventional radiology of the pleural space.

PMID- 7729116
TI  - Superparamagnetic iron oxide imaging of focal liver disease.
AB  - The use of iron oxide as a superparamagnetic contrast agent for magnetic
      resonance imaging of the liver has been described previously. When administered
      intravenously, superparamagnetic iron oxide (SPIO) is sequestered by the
      reticuloendothelial system causing significant shortening of the T2-relaxation
      time. The majority of the contrast is taken up by the reticuloendothelial tissue
      of the liver. Since tumours have reduced or absent reticuloendothelial tissue the
      effect on relaxation time is minimal and signal intensity differences between
      tumour and liver are increased. AMI 25 (Laboratoire Guerbet, Paris) is a
      colloidal solution of ferrous and ferric oxides. We have performed MR examination
      of the liver in 16 patients with focal liver lesions using AMI 25 as a
      superparamagnetic contrast agent. Our results indicate that SPIO significantly
      increases the conspicuity of focal lesions and the effect is greatest in
      malignant tumours. We observed no adverse reaction to this contrast agent.

PMID- 7729117
TI  - A histological basis for the 'sonographic snowstorm' in opportunistic infection
      of the liver and spleen.
AB  - We report 3 cases of opportunistic infection of the liver and spleen due to
      Pneumocystis carinii, Candida albicans and Aspergillus with an unusual but
      similar sonographic appearance. In the patient with Pneumocystis we report for
      the first time this same appearance in the bowel and pleura. Histology showed
      either extensive fibrosis or focal fibrinous exudates as the underlying cause.
      Calcification, though present, was scanty and was not thought to be the likely
      explanation for the appearances.

PMID- 7729118
TI  - Update: abdominal tuberculosis--unusual findings on CT.
AB  - To update our knowledge of abdominal tuberculosis as manifested on computed
      tomography (CT), we reviewed the CT scans of 12 patients with proven abdominal
      tuberculosis. The nature, range and extent of abdominal involvement was
      determined. The CT findings were compared to those reported in the literature.
      The aetiologic agent was Mycobacterium tuberculosis in all patients. One patient
      had an increased risk because of AIDS. In nine patients, tuberculosis was limited
      to the abdomen, and three patients had previously unknown thoracic tuberculous
      disease. Characteristic features in our patients included low density ascites and
      uncommon patterns of adenopathy. Findings reported to be typical in abdominal
      tuberculosis were present in only five of our 12 patients. Unusual findings in
      our patients included solitary and multiple pelvic, adrenal, splenic and hepatic
      lesions. In six of 12 patients, those findings mimicked malignancy. We conclude
      that knowledge and early recognition of these unusual manifestations of abdominal
      tuberculosis should help to optimize clinical management of the disease and avoid
      misdiagnosis.

PMID- 7729119
TI  - Metastatic cervical nodes in papillary carcinoma of the thyroid: ultrasound and
      histological correlation.
AB  - The ultrasound appearances and histological correlation of metastatic cervical
      lymph nodes in 20 patients with papillary carcinoma of the thyroid are presented.
      The majority of the malignant nodes were homogeneous (81.2%), hyperechoic (87.5%)
      compared to adjacent sternomastoid muscle and 68.7% showed peripheral punctate
      calcification on US and histology. Histology revealed that the peripheral
      echogenic foci seen within the nodes on US correlated with psammoma bodies which
      are characteristic for papillary carcinomas, highlighting the importance of
      recognizing peripheral punctate calcification in the cervical nodes as a useful
      sign for the diagnosis of metastatic papillary carcinoma of the thyroid.

PMID- 7729120
TI  - The role of venous colour flow Doppler to aid the non-diagnostic lung scintigram
      for pulmonary embolism.
AB  - Sixty patients admitted with a clinical diagnosis of pulmonary embolism underwent
      a prospective analysis of the value of lung ventilation/perfusion scintigraphy
      and lower limb colour flow venous Doppler. Twenty-two per cent of scintigrams
      gave a high probability of pulmonary embolus (PE) and 45% a low
      probability/normal. The remainder were classed as indeterminate scintigrams (33%)
      and of these, 55% showed leg thrombi on the ultrasound scan. These patients were
      therefore treated by anticoagulation. A small number of the low probability
      scintigrams also proved to have lower limb thrombi by ultrasound. As a result of
      these two investigations just over half of these patients with a clinical
      diagnosis of PE were anticoagulated (31 out of 60). In 62% of these the
      ultrasound suggested thrombi confined to the calf as a source of PE.

PMID- 7729121
TI  - Sonographic evaluation of intramuscular ganglia.
AB  - The study presents the ultrasound appearance of the intramuscular ganglia arising
      from the superior tibio-fibular joint. An oval, anechoic septated mass with
      distal sound enhancement in the antero-lateral aspect of the leg was seen in five
      examined patients. In all the cases, ultrasound-guided needle aspiration was
      performed and viscous fluid characteristic of ganglia was obtained. All the
      patients were treated by surgical excision of mass. Local recurrence, which
      occurred in three cases, was confirmed by ultrasound. The study indicates that
      ultrasound is useful in diagnosing intramuscular ganglia, in planning the
      treatment, and in the follow-up examination. Ultrasound-guided needle aspiration
      is a helpful technique in confirming the diagnosis.

PMID- 7729122
TI  - Percutaneous transluminal angioplasty in femoral artery occlusions: primary and
      long-term results in 107 claudicant patients using femoral and popliteal
      catheterization techniques.
AB  - To assess the impact of percutaneous transluminal angioplasty (PTA) of occluded
      femoral arteries, a prospective study of 107 claudicant patients was performed. A
      total of 117 limbs were treated and were followed for 1-36 months; the mean
      length of treated occlusions was 7.4 cm (range 2-25 cm). Eighty-nine
      recanalizations were performed using antegrade femoral and 28 using the
      retrograde popliteal catheterization technique. With logistic regression a short
      length of occlusion correlated favourably with early success. Including rePTAs
      and applying standardized criteria, survival analysis with the Kaplan-Meier
      method revealed a 3-year secondary patency rate of 55% for all the treated limbs.
      The following factors had negative influence on primary patency after successful
      recanalization; presence of soft thrombotic material in the recanalized artery
      segment and the presence of focal dissections after PTA. In univariate and
      multiple logistic regression analysis, male gender and a lesser extent of the
      atherosclerotic disease (assessed by the number of diseased vessels in the
      treated limb) correlated with a lower frequency of PTA procedure complications.
      There was no statistically significant difference in the complications, in the
      primary success or in the long-term results using either the femoral or popliteal
      route. However, the popliteal approach improved the early success of the
      originally antegrade access group by 6% and increased by about one-fifth the
      number of patients considered technically feasible for PTA in femoral artery
      occlusions. PTA can be used in femoral artery occlusions up to 10 cm long and it
      is especially suitable in femoral artery occlusions not exceeding 5 cm in length.
      PTA can be tried in femoral artery occlusions exceeding a length of 10 cm if
      operative treatment is not suitable.

PMID- 7729123
TI  - The use of expandable metal stents in transplant renal artery stenosis.
AB  - The management of resistant transplant renal artery stenosis (TRAS) poses
      difficult problems. There is no consensus on the most appropriate course of
      action if severe stenosis recurs despite repeated percutaneous transluminal
      balloon angioplasty (PTA). Expandable metallic vascular stents have been
      increasingly successful as an adjunct to PTA in the coronary and peripheral
      circulation and more recently in the management of resistant native renal artery
      stenosis. We report four cases in which such stents were successfully used to
      treat resistant stenosis in transplant renal arteries. The cases illustrate the
      range of problems that may be caused by TRAS, from resistant hypertension to
      impending graft failure. The stents were successfully deployed in all four
      patients. One patient had an acute stent thrombosis successfully treated with
      immediate thrombolysis and two patients required repeat stenting. In all the
      cases there was arrest or slowing of previously aggressive recurrent TRAS and at
      the close of follow-up (4-24 months) all patients had adequate stable allograft
      function, and satisfactory blood pressure control including the one patient with
      a significant residual stenosis.

PMID- 7729124
TI  - Renal transplant vein occlusion: an early diagnostic sign?
AB  - We report new Doppler ultrasound findings in two patients with renal vein
      thrombosis and obstruction following renal transplantation. In both cases there
      was a marked reduction in the systolic peak with relatively normal diastolic flow
      in the intrarenal arterial waveforms. Venous flow was still detectable at the
      renal hilum in both cases, and throughout the graft in one case. We suggest that,
      in the absence of signs of proximal renal artery stenosis, small amplitude
      arterial waveforms with a depressed systolic peak and maintained diastolic flow,
      despite intrarenal venous flow, represent renal vein thrombosis in evolution or
      renal vein obstruction. These findings merit early surgical exploration.

PMID- 7729125
TI  - Benign biopsies in the prevalent round of breast screening: a review of 137
      cases.
AB  - In the first round of the National Health Service Breast Screening Programme,
      35,533 women attended for screening at the two breast screening units served by
      St Bartholomew's Hospital. Further assessment was necessary in 2212 women (6.2%),
      of whom 412 (1%) subsequently underwent surgical biopsy. Of these 137 had benign
      lesions. The predominant mammographic abnormality leading to biopsy was
      microcalcification in 55, a mass in 48, parenchymal asymmetry in 18 and
      architectural distortion in 16. Histology revealed fibrocystic change in 66,
      fibroadenoma in 27, radial scar/complex sclerosing lesion in 23, atypical ductal
      hyperplasia only in eight, and a variety of unusual benign lesions in 13. In an
      attempt to determine criteria which would minimize unnecessary biopsy of benign
      lesions in future, the mammographic and cytological features of these benign
      lesions were reviewed and compared with the final histology. The most common
      diagnostic problems were clustered and variable microcalcification, the radial
      scar/complex sclerosing lesion, and mammographic features shown to be atypical
      hyperplasia on histology.

PMID- 7729127
TI  - Radiation dose to the lens from coronal CT scanning of the sinuses.
AB  - The radiation dose to the lens of the eye was measured using thermoluminescent
      dosimeters placed over the eyelids of 82 patients undergoing coronal CT
      examinations of the sinuses at six CT scanning units in the West of Scotland. The
      lens doses were dependent upon the mAs setting of the scanner, with a mean lens
      dose of 70.3 mGy at 475 mAs, 17.6 mGy at 210 mAs and 4.7 mGy at 30 mAs. All
      coronal CT examinations of the sinuses requested for the planning of functional
      endoscopic sinus surgery should use a low mAs technique. The mAs setting should
      be locally agreed between the radiologist and ENT surgeon, depending on their
      joint assessment of scan quality.

PMID- 7729126
TI  - Hyperphosphataemic tumoral calcinosis in Bedouin Arabs--clinical and radiological
      features.
AB  - In the first report of Bedouin Arabs with tumoral calcinosis, three Saudi Arabian
      male siblings and their female first cousin with the condition are described. In
      tumoral calcinosis the majority of cases are familial. These patients had
      associated hyperphosphataemia with normal renal function. The characteristic
      appearance of periarticular soft tissue calcified masses was present. Two of the
      cases developed calcific myelitis of long bones--a recognized complication of the
      disease. Two have widespread arterial calcification, which has not previously
      been described. Two cases have other unusual features; one has a calcified mass
      which has destroyed the blade of the scapula, whilst another developed a large
      tumoral mass on the posterior aspect of the knee.

PMID- 7729128
TI  - Case report: radiological appearance of colonic stricture associated with the use
      of nonsteroidal anti-inflammatory drugs.

PMID- 7729129
TI  - Case report: benign giant cell tumour associated with Paget's disease of bone.

PMID- 7729130
TI  - Case report: renal involvement in primary Sjogren syndrome--a rare cause of renal
      pseudotumour.

PMID- 7729131
TI  - Case report: fetus-in-fetu--imaging, surgical and pathological findings.

PMID- 7729132
TI  - Percutaneous biopsy of pancreatic masses in patients with biliary metal stents:
      the snags!

PMID- 7729133
TI  - Gastroduodenal artery pseudoaneurysm presenting with obstructive jaundice.

PMID- 7729134
TI  - DNA ploidy in testicular germ cell tumors: can an atypical seminoma be
      identified?
AB  - Recent immunohistochemical and DNA ploidy analyses indicate that seminoma serves
      as a precursor to nonseminomatous germ cell tumors. It is believed that tumor
      progression from classical seminoma to nonseminoma is accompanied by inactivation
      and deletion of genetic material, and that these deletions are reflected in DNA
      ploidy. Twenty-three primary testicular germ cell tumors were studied by DNA flow
      cytometry to investigate whether a proposed histologic intermediate "atypical
      seminoma" (AS) could be separated from classical seminoma by ploidy analysis. The
      mean DNA indices (DI) for classical seminoma (N = 16), atypical seminoma (N = 5),
      and nonseminoma (N = 2; both embryonal carcinoma) were 1.53, 1.34, and 1.35,
      respectively. When a single "outlier" case of atypical seminoma was removed from
      consideration the mean DI for the AS rose to 1.45. This data is consistent with
      the interpretation of atypical seminoma as an intermediate between classical
      seminoma (CS) and embryonal carcinoma (ES). It suggests that genetic deletions
      characterizing progression from CS to nonseminoma may, in part, already be extant
      in atypical seminoma.

PMID- 7729135
TI  - Mortality experience, 30-days and 365-days after admission, for the 20 most
      frequent DRG groups among Medicare inpatients aged 65 or older in Connecticut
      hospitals, fiscal years 1991, 1992, and 1993.
AB  - This report presents mortality rates following inpatient admissions for the 20
      most frequent DRG categories among Medicare inpatients aged > or = 65 years at
      Connecticut acute-care hospitals during the three-year period from fiscal year
      1991 to fiscal year 1993. We provide frequency distributions of the 30-day and
      365-day mortality rates among these 20 DRG categories. Among the 199,680
      discharges of elderly Medicare beneficiaries within the 20 most frequent DRG
      categories in the three-year study period, the crude 30-day mortality rate was
      9.51%; the crude 365-day mortality rate was 28.40%. By gender, the crude 30-day
      mortality rate for women was 8.78%; the corresponding rate for men was 10.48%.
      This gender mortality differential occurred despite a significant age
      differential; on average, the females were 2.5 years older than the males. By age
      group, the crude mortality rates were: age 65-74 years, 6.66%; age 75-84 years,
      9.80%; age > or = 85 years, 15.25%. The crude mortality rates for the DRG
      categories were found to be stable over the three-year study period.

PMID- 7729136
TI  - Managed care: a white paper.

PMID- 7729137
TI  - Adapting to the Stark II antireferral ban: a practical analysis of the
      prohibition and exceptions.

PMID- 7729138
TI  - Medicine on stage in the Gilbert and Sullivan operas.

PMID- 7729139
TI  - Futile medical care.

PMID- 7729140
TI  - What's missing in our definitions of primary care?

PMID- 7729141
TI  - Night thoughts on end-of-the century medicine.

PMID- 7729142
TI  - Befriending the suicidal in Hong Kong and China.

PMID- 7729143
TI  - Letters across the Atlantic.

PMID- 7729144
TI  - Suicide and aging: lessons from the nursing home.

PMID- 7729145
TI  - Prison suicide: an overview and guide to prevention (Part 1).

PMID- 7729147
TI  - Altruism in hotline volunteers.

PMID- 7729146
TI  - Youth suicide: trends indicate increasing hopelessness in young males.

PMID- 7729148
TI  - Defining crisis and emergency.
AB  - All too often, a crisis is responded to inappropriately, as if it were an
      emergency. Similarly, an emergency is often inappropriately treated with crisis
      intervention. Resources are wasted or the client receives unsuitable care. It
      becomes clear when reading the literature that no consensus has been achieved
      regarding definitions of the terms "crisis" and "emergency." This article argues
      that the terms are not interchangeable, offers specific definitions of each, and
      discusses some of the implications of the definitions. The confusing situations
      which arise in clinical practice may be clarified by the use of these
      definitions, and it is hoped that they will lead to more appropriate clinical
      decision making.

PMID- 7729149
TI  - Understanding deliberate self-harm: the patients' views.
AB  - Patients were asked to explain why they had attempted suicide, by spontaneous
      description and by the use of lists of problems and motives presented to them.
      They were also asked what help they would have accepted before the event, and
      what the consequences of the suicide attempt were. The main motive for attempting
      suicide mentioned was an acute and unbearable state of mind. Interpersonal
      (manipulative) motives were of much less importance to the patients. In contrast,
      the problems which patients thought had an influence on what they had done were
      mainly interpersonal problems and, to a lesser degree, health problems.
      Especially younger individuals saw interpersonal difficulties as the main
      problems. Many patients reported that in the suicidal crisis they would not have
      been prepared to accept help. Most felt the suicide attempt had positive
      consequences for them.

PMID- 7729150
TI  - Icons of ancient suicide: self-killing in classical art.
AB  - Attitudes to suicide differ between societies, and also change with time. 104
      items of ancient art that show suicide have been examined and catalogued. These
      icons, the most distinctive of which are discussed here, confirm the view
      suggested by literary sources that in the Graeco-Roman world self-killing was
      preferably seen as a deliberate, resolute, and heroic act.

PMID- 7729151
TI  - Reflections on the statistical rarity of suicide.

PMID- 7729152
TI  - Conference report: bioethics in eastern Europe--bioethics vs suicide.

PMID- 7729153
TI  - Hemophilus influenzae bacteremia in elderly men with Kaposi's sarcoma: two case
      reports and a review of the literature.
AB  - Hemophilus influenzae is a common pathogen responsible for respiratory
      infections, meningitis, and bacteremia in children, and a rare cause of
      bacteremia in adults. We report two cases of H. influenzae bacteremia in elderly
      men with Kaposi's sarcoma. Both of the patients described are elderly men with no
      other stigmata of the acquired immune deficiency syndrome. Both Kaposi's sarcoma
      of the elderly and adult H. influenzae bacteremia are relatively uncommon, and
      the coappearance of these syndromes may suggest a common immune defect
      predisposing to these syndromes, or Kaposi's sarcoma may provide a portal of
      entry for this organism. We suggest that patients with Kaposi's sarcoma who may
      have bacteremia receive appropriate antibiotic treatment for H. influenzae until
      a causative agent is isolated.

PMID- 7729154
TI  - Disseminated histoplasmosis presenting as tongue nodules in a patient infected
      with human immunodeficiency virus.
AB  - A 39-year-old woman infected with human immunodeficiency virus had disseminated
      histoplasmosis that presented with nodules on her tongue. This is the seventh
      reported case of biopsy- and/or culture-proven oropharyngeal histoplasmosis in
      patients with acquired immunodeficiency syndrome. We review those previous
      reports and discuss the clinical features of disseminated histoplasmosis in
      patients with acquired immunodeficiency syndrome.

PMID- 7729155
TI  - Photodistributed hypertrophic lichen planus in association with acquired
      immunodeficiency syndrome: a distinct entity.
AB  - The cutaneous manifestations of human immunodeficiency virus infection include
      papulosquamous diseases, viral and fungal infections, and neoplastic disorders.
      Eczematous photosensitivity disorders have been reported in patients infected
      with the human immunodeficiency virus. We describe a patient with advanced
      acquired immunodeficiency syndrome who developed photodistributed hypertrophic
      lichen planus. We believe this is a distinct cutaneous manifestation of human
      immunodeficiency virus infection.

PMID- 7729156
TI  - Papular mucinosis and human immunodeficiency virus infection.
AB  - Cutaneous mucin deposition occurs both as an isolated phenomenon and in patients
      with various systemic disorders. Among these are endocrinopathies (eg, hypo- and
      hyperthyroidism), malignancy (mycosis fungoides), connective tissue disorders
      (lupus erythematosus), and infectious diseases (scleredema associated with upper
      respiratory tract infection). We present a case of papular mucinosis in a patient
      infected with the human immunodeficiency virus. This case represents the third
      report of these disorders coexisting.

PMID- 7729157
TI  - Special issue: AIDS in dermatology.

PMID- 7729158
TI  - The role of ocular disturbances in the differentiation of idiopathic vitiligo
      from contact leukoderma.

PMID- 7729159
TI  - Cutaneous manifestations of childhood acquired immunodeficiency syndrome and
      human immunodeficiency virus infection.

PMID- 7729160
TI  - A dermatologic diary. Portrait of a practice.

PMID- 7729161
TI  - The human immunodeficiency virus.
AB  - Infection with the human immunodeficiency virus is now a worldwide pandemic,
      transmitted through contact with infected body fluids, particularly during
      heterosexual intercourse. Infection in adults is followed by an asymptomatic
      period that lasts several years, after which continued destruction of the immune
      system renders the individual susceptible to multiple opportunistic infections.
      Antiviral therapy has been shown to prolong patient survival. However, viral
      resistance has limited the options available to clinicians. Until a truly
      effective antiviral agent or immune-modulator is developed, efforts to change
      risky sexual practices will remain the most important resource in limiting the
      spread of this infection.

PMID- 7729162
TI  - Fundamental basic science of human immunodeficiency virus.

PMID- 7729163
TI  - Cutaneous diseases in human immunodeficiency virus-infected patients referred to
      the UCLA Immunosuppression Skin Clinic: reasons for referral and management of
      select diseases.
AB  - Many nondermatologist physicians have become skilled at identifying and treating
      certain human immunodeficiency virus-related skin diseases. They are reserving
      referrals primarily for diagnostically or therapeutically challenging skin
      disorders. Our purpose was to study the reasons for referral of human
      immunodeficiency virus-infected patients, and to review the management of select
      diseases. One-hundred and fifty human immunodeficiency virus-positive outpatients
      were evaluated consecutively for cutaneous diseases that prompted their referrals
      by nondermatologist physicians. The three most common reasons for referral were
      eczematous dermatoses (32 percent), molluscum contagiosum (24 percent), and
      Kaposi's sarcoma (21 percent). There are differences in the prevalence of
      cutaneous disorders in human immunodeficiency virus-positive patients referred
      for dermatologic intervention compared to that in the general human
      immunodeficiency virus-positive population. Patients with seborrheic dermatitis,
      dermatophytosis, and xerosis were less commonly referred than expected based on
      their reported prevalence in the general human immunodeficiency virus-positive
      population. In contrast, molluscum contagiosum, warts, and Kaposi's sarcoma were
      seen more frequently in our referred cohort.

PMID- 7729164
TI  - The brain dopaminergic system. Pharmacological, behavioural and
      electrophysiological studies.
AB  - The kindling phenomenon is a good example of the effect of multiplicity on
      response increment processes in the nervous system. The electrical potentiation
      resembles pharmacological sensitization. An intermittent regimen is essential for
      a progressive augmentation of the behavioural response in both conditions. Nigro
      striatal dopaminergic sensitization by on and off anti-dopaminergic drugs has
      been suggested as a model for development of tardive dyskinesia (TD) and
      sensitization of the meso-limbic dopaminergic system either by repeated
      stimulation with agonists or by environmental stressors has been proposed to
      model psychotic development in schizophrenia. The present thesis addresses the
      implications of intermittent influences on the brain dopaminergic systems for the
      development of pathological behaviours. For this purpose new rat models have been
      developed both for studying the effects of the treatment schedule of neuroleptics
      on the development of oral hyperactivity and for studying the effects of
      intermittent electrical stimulations of the ventral tegmental area (VTA) housing
      the meso-limbic dopamine (DA) cells. A long-lasting/permanent kindling-like
      sensitization to the dyskinetic inducing side-effects of classical neuroleptic
      drugs following intermittent opposed to continuous treatment has been
      demonstrated. This sensitization is proposed to represent an animal model for TD.
      The significance of receptor profiles, the effects of pharmacological
      interventions and the possible relation to the GABAergic and cholinergic systems
      are discussed. Intermittent electrical activation of the cells in the VTA
      resulted in a syndrome characterized by a hypersensitive response to electrical
      or pharmacological dopaminergic provocation combined with abnormal social
      interactions. This new animal model may have implications for the understanding
      of the pathogenesis of schizophrenia. Hypotheses are proposed for the meaning of
      dopaminergic sensitization both in the development of persisting dyskinetic side
      effects related to neuroleptic treatment and in the development of schizophrenia.

PMID- 7729165
TI  - Perceived health in three groups of elderly people. A validity study of the
      Danish version of the Nottingham Health Profile.
AB  - The Nottingham Health Profile (NHP) is a measure of physical, emotional and
      social distress. It was developed in the United Kingdom and has been adapted and
      translated into Danish. The Danish version of the NHP has been shown to be
      reliable. In order to establish the validity of the measure it was administered
      to three groups of people, all over the age of 60, who were expected to differ in
      health status. These groups consisted of 120 persons attending fitness classes on
      a regular basis, 64 patients with low back pain and/or pain in the lower
      extremities referred by their general practitioner for treatment at an out
      patient clinic and 72 patients with osteoarthrosis of the hip awaiting hip
      replacement operation. As predicted, the patients awaiting hip replacement
      surgery scored higher (indicating greater distress) on all six sections of the
      measure than did the patients attending the out-patient clinic. Both these groups
      scored higher on all sections of the NHP than the fitness class members. It is
      concluded that the Danish version of the NHP has been found valid insofar as it
      shows expected differences between three groups of elderly people.

PMID- 7729166
TI  - Increasing age-specific incidence of hip fractures in a Danish municipality.
AB  - From 1970 to 1986 a total of 4578 hip fractures were registered in persons > or =
      40 years in a Danish urban municipality. During that period, the annual number
      almost tripled. The statistical analysis revealed an increase in the age-specific
      incidence for both females and males (p < 0.0001). Furthermore, the number of
      fractures increased due to demographic aging. The overall incidence for
      individuals > or = 40 years increased 9-10% annually; from 2.1 to 5.4 per 1.000
      females, and from 0.9 to 2.1 per 1.000 males. The female:male ratio was 2.8
      without changes over time. If the observed increase in incidence is extrapolated
      to the next 17 years, a doubling of the annual number of fractures is predicted
      by the year 2002, whereas an unchanged incidence would result in a 20% increase
      in number.

PMID- 7729167
TI  - Plasmodium falciparum malaria parasite exoantigens: their role in disease and in
      immunity.

PMID- 7729168
TI  - Late postoperative hypoxaemia. Mechanisms and clinical implications.

PMID- 7729169
TI  - Pneumococcal polysaccharide antigens: capsules and C-polysaccharide. An
      immunochemical study.

PMID- 7729170
TI  - Immunochemical determination of amniotic fluid acetylcholinesterase in the
      antenatal diagnosis of open neural tube defects.
AB  - The aims of the studies reviewed were 1) to identify the molecular forms of
      acetylcholinesterase encountered in amniotic fluid from pregnancies with a normal
      fetus and those with a fetal open neural tube defect or other fetal malformation
      and, 2) to raise and characterize antibodies against human acetylcholinesterase
      and to identify those useful for immunochemical determination of amniotic fluid
      acetylcholinesterase where there is a fetal open neural tube defect. Eleven
      monoclonal antibodies and one polyclonal rabbit antibody were evaluated with
      regard to their clinical usefulness in the antenatal diagnosis of open neural
      tube defects. One of these, the monoclonal antibody 4F19, preferentially bound
      acetylcholinesterase from human brain and identified better than the others
      amniotic fluid samples from pregnancies with a fetal open neural tube defect (I,
      II). The monoclonal antibody 4F19 was used in an enzyme antigen immunoassay whose
      performance was found to be similar to that of the polyacrylamide electrophoretic
      gel test for acetylcholinesterase determination (III). However, the 4F19 enzyme
      antigen immunoassay is simpler, more rapid and less technically demanding than
      the gel test, and furthermore, it gives a quantitative result. The 4F19 enzyme
      antigen immunoassay was also compared with the alpha-fetoprotein test, normally
      used as the primary test for the antenatal diagnosis of open neural tube defects.
      The 4F19 enzyme antigen immunoassay performed better than the alpha-fetoprotein
      test, but the best performance was found for a combination of the two tests (VI).
      A positive result can be found using the combined tests for conditions other than
      open neural tube defects, e.g. abdominal wall defects, intrauterine fetal death
      and other fetal malformations. These conditions can often be discerned by
      ultrasound examination. However, combining the result of the 4F19 enzyme antigen
      immunoassay with the result of an enzyme antigen immunoassay for
      butyrylcholinesterase makes a discrimination between these conditions possible
      (V). The diagnostic implications of the above procedures are evaluated and
      specific recommendations concerning their use are given.

PMID- 7729171
TI  - Secretory otitis media in schoolchildren. Is screening for secretory otitis media
      advisable?

PMID- 7729172
TI  - Missing persons: women in child welfare.
AB  - This article examines the presence, visibility, and influence of women in the
      child welfare system, as clients, workers, and decision makers, and explores
      impediments to the reconceptualization of child welfare as a women's issue. Four
      directions for change are discussed, including consciousness-raising, organizing,
      infusing of child welfare with feminist forms, and reshaping feminist thought to
      include class and race as central issues.

PMID- 7729173
TI  - Child abuse and neglect in Ontario: incidence and characteristics.
AB  - This article presents descriptive findings from the Ontario Incidence Study of
      Reported Child Abuse and Neglect (OIS). OIS is the first Canadian study to
      examine the incidence and characteristics of reported maltreatment. The study is
      based on a survey form completed by child protection workers on a representative
      sample of 2,447 investigated children. OIS found an incidence rate of reported
      maltreatment of 21 per thousand children, and a 27% substantiation rate. These
      rates are compared to those in the United States.

PMID- 7729174
TI  - My cheque and my children: the long road to empowerment in child welfare.
AB  - This article is based upon a two-year research project in a government child
      welfare agency in British Columbia involving frontline child welfare workers and
      women who are single parents. Based upon previous research with public child
      welfare workers, the authors developed several principles that emphasized the
      importance of female clients and frontline workers having the power to shape
      practice according to their joint plans. The article reports on the achievements
      of women who are single parents and of workers once they are given the freedom to
      redevelop services. The underlying concept--empowerment--is reviewed and a
      comprehensive definition of the term, based upon client and worker empowerment,
      is proposed.

PMID- 7729176
TI  - [Chemistry of silicones].

PMID- 7729175
TI  - [History of breast augmentation].

PMID- 7729177
TI  - [Histological aspect of the periprosthetic environment].

PMID- 7729178
TI  - [Autoimmune diseases related to silicone breast prostheses].

PMID- 7729179
TI  - [Breast prosthesis: legal responsibility and regulations].

PMID- 7729180
TI  - [Manufacturing standards of breast prostheses].

PMID- 7729181
TI  - [Chronic arterial rejection and immunogenicity of the extracellular matrix in iso
      , allo- and xenograft in rats].
AB  - Both allografts and xenografts chronic arterial injection results in arterial
      wall dilation and rupture, making them unsuitable for long term-arterial
      replacement in vascular surgery. Cells in the arterial wall carry major antigenic
      determinants and can be removed by detergent treatment to produce a graftable
      proteic matrix tube. We compared the patency and the macroscopic and microscopic
      morphological changes that occurred in sodium dodecyl sulfate (SDS)-treated and
      untreated arterial iso-, allo- and xenografts, two months after implantation in
      63 rats. We quantified elastin, collagen and nuclear density in the three layers
      of the grafts by morphometric methods. SDS treatment removed endothelial and
      smooth muscle cells, but preserved elastin and collagen extracellular matrix. All
      arterial xenografts, whether SDS-treated or untreated, were aneurysmal two months
      after grafting, with loss of the medial cellular and extracellular components. In
      allografts, SDS treatment prevented dilation, reduced aventitial inflammatory
      infiltration and preserved medial elastin. SDS-treated allografts had an evenly
      distributed, non-inflammatory intimal thickness that was richer in elastin fibers
      than untreated allografts. These results suggest an interspecies, but not an
      intraspecies, graft antigenicity of arterial extracellular matrix. SDS treatment
      prevented chronic rejection of the arterial allograft and led to the
      proliferation of an elastin-rich and adapted intima.

PMID- 7729182
TI  - [Correction of bilirubin glucuronyl transferase in Gunn rats by gene transfer in
      the liver using retroviral vectors].
AB  - The in vivo procedure for retrovirus-mediated gene transfer into rat liver allows
      genetic modification of 1 to 5% hepatocytes and the expression of a foreign gene
      for more than one year. We have used the Gunn rat as a model of the human Crigler
      Najjar type I syndrome to assess the pertinence of this approach for the
      treatment of severe liver genetic diseases. After transfer of the rat bilirubin
      uridin diphosphate-glucuronosyl transferase cDNA into hepatocytes, 15 Gunn rats
      were examined during several months and sacrificed. Bilirubin glucuronides were
      excreted in the bile of all recipients, and serum bilirubin levels were
      significantly reduced in the treated population. The decrease was more than 40%
      in 5 of the 15 rats. These date showed that long term expression of a therapeutic
      protein can be obtain after in vivo retrovirus-mediated gene transfer into the
      liver.

PMID- 7729183
TI  - [Model of "bridge" graft between the cervical spinal cord and biceps muscle using
      a peripheral nerve autograft. Study in adult rats].
AB  - The authors present, in the adult rat, a model of reconnection between an injured
      cervical spinal cord (C5) and the biceps brachii muscle (BB) previously
      denervated, by means of an autologous peripheral nerve segment (PNG). The study
      includes 30 rats shared into 4 principal groups: A) the denervation of BB by
      transection and ligature of the musculocutaneous nerve (MCN); B) transection and
      immediate suture of the MCN; C) transection/ligature of the MCN and insertion of
      a PNG both into the cervical spinal cord and into the BB; D) transection of the
      MCN, ligature of its proximal tip, insertion of one end of a PNG into the
      cervical spinal cord and suture of the other end with the distal stump of the
      MCN. Assessment of the following parameters were performed, in all animals, three
      months after the grafting procedure: 1) the muscle strength by using the toilet
      test; 2) the weight of the experimental BB in comparison to the contralateral BB;
      3) the response (contraction) of the BB under electrical stimulation of either
      the MCN or the PNG; 4) the histological appearance of the BB; 5) the presence of
      retrogradely labelled neuronal somata in the cervical spinal cord following
      application of horseradish peroxidase (HRP) to the MCN or to the GNP. These
      parameters of evaluation have at first been validated in two cases already known:
      the chronic denervation of the BB (group A), and the peripheral nerve lesion
      (group B). Once these cases validated, they have been used to appreciate the
      muscular reinnervation by axonal growth from the spinal cord.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7729184
TI  - [Intrasplenic transplantation of hepatocytes in spf-ash mice with congenital
      ornithine transcarbamylase deficiency].
AB  - The only curative treatment for enzymatic deficiency such as Ornithine
      transcarbamylase (OTC) deficiency is liver transplantation. We have studied
      hepatocyte transplantation as alternative therapy in spfash mouse, the animal
      mode of OTC deficiency. Hepatocytes were obtained from C57BL/6J strain mice
      (normal OTC activity). About 2 x 10(6) hepatocytes in 0.1 ml were injected in the
      spleen of recipient mouse. We then studied: ammonemia, urinary orotate, spleen
      OTC activity, liver OTC activity, histological presence of hepatocytes in the
      spleen, immunohistochemical OTC staining in liver and spleen hepatocytes. In
      syngeneic hepatocyte transplantation (C57 > C57) functional transplanted
      hepatocytes were found in the spleen over 5 months after transplantation. In
      allogeneic transplantation (C57 > spfash) without immunosuppression, hepatocytes
      were rejected in 3 days. With cyclosporine immunosuppression, hepatocyte survived
      12 days and showed OTC activity. A few transplanted hepatocytes with OTC activity
      migrated from spleen of liver. Metabolic disorder were not corrected. This
      technically easy method (compared to whole liver transplantation) demonstrated 2
      problems: reject in allogeneic transplantation and the small amount of injected
      enzyme.

PMID- 7729185
TI  - [Salvage esophagoplasty using free jejunal transplant after repeated failure of
      other esophagoplasties. 25 cases].
AB  - Salvage oesophagoplasty using a free jejunal transplant is the ultimate
      reconstruction possible after repeated failures using the classic procedures of
      oesophagoplasty. The free jejunal transplant appears to be the best choice.
      Twenty-five free jejunal transplants were performed by the same surgeon for such
      reconstructions including 13 cases involving benign lesions and 12 cases of
      cancer. There were no post-operative death and none of the transplantations was a
      complete failure although three cases of stenosis and fistulization occurred.
      Several recommendations can be made: save the existing digestive tract, redissect
      the residual digestive plasty and pull it up. The residual digestive flap can be
      examined by opacification or endoscopically in order to evaluate its length. An
      arteriography of the pediculated plasty gives information on its vascularization.
      A free jejunal graft can safely cover 25 to 30 cm. When possible, residual
      plasties should be positioned subcutaneously. The reconstruction of the cervico
      thoracic oesophagus usually requires a vascular bypass with a saphene graft. In
      difficult cases, it may be necessary to remove a part of the sternal manubrium
      and the head of the clavicular bone in order to avoid compressing the jejunal
      graft. When the length of the reconstruction is greater than 30 cm, a long
      jejunal transplant with two pedicules (1 pedicule revascularized from the
      cervical vessels and the other pedicule from the internal thoracic vessels) is
      needed. An alternative technique would be a free antebrachial flap (six cases
      operated with two post-operative deaths at 6 weeks and two fistulas).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7729186
TI  - ["Piggyback" method in hepatic transplantation].
AB  - Using the traditional technique for liver transplantation, there are two supra
      and subhepatic anastomoses to the vena cava. With the piggy-back method, the
      donor's inferior vena cava is implanted terminolaterally into the recipient's
      inferior vena cava. The aim of this work was to evaluate results in two matched
      groups. PATIENTS AND METHODS. From June 1992 to May 1993, 13 patients underwent
      piggy-back liver transplantation (group 1) and 14 others underwent traditional
      liver transplantation (group 2). There were 17 men and 10 women, mean age 48
      years (range 25-65 years). There was no significant difference between the groups
      for age, sex, indications, number of rejections and retransplantations. RESULTS.
      There were no deaths in group 1 and 2 deaths in group 2 within the first 30 days
      postoperatively. There was no significant difference between groups 1 and 2 for
      duration of cold ischaemia (552 +/- 323 vs 463 +/- 345 min respectively), the
      number of packed cell transfusions (9.8 +/- 11 vs 11.1 +/- 5.5), duration of the
      operation (474 +/- 151 vs 500 +/- 95 min), duration of anastomosis (56 +/- 17 vs
      66 +/- 20 min), creatinine levels at day 30 (140 +/- 79 vs 200 +/- 145 min). But
      there was a significant difference in the anhepatic phase (56 +/- 17 vs 66 +/- 20
      min). CONCLUSION. Unexpectedly, there was no significant difference between the
      two types of transplantation with the exception of the anhepatic phase.

PMID- 7729187
TI  - [Encapsulating peritonitis after chronic peritoneal dialysis. Apropos of 3
      cases].
AB  - Encapsulating peritonitis has been recognized as a life threatening, evolutive
      complication of chronic ambulatory peritoneal dialysis. Three cases are reported.
      Etiological factors are multiple, the diagnosis is suspected on peritoneal
      clinical signs, partial small bowel obstruction and impaired ultrafiltration.
      Barium studies and CT scan show small bowel enclosed within a peritoneal cocoon,
      prolonged transit time, wall thickening and a trabeculated fluid collection.
      Laparotomy confirms the diagnosis and reveals the pathological stage of disease.
      The surgical treatment consists of striping away the encapsulating membrane if
      possible while multiple incisions and loops release are indicated in other cases.
      The prognosis is poor unless an early surgical treatment is done.

PMID- 7729188
TI  - [Conservative treatment of splenic injuries in adults. Conservation or surgery?].
AB  - A preservative attitude towards splenic traumatism is globally no more discussed.
      But the best way to succeed for the general surgeon has to be precise: non
      operative either coeliotomy for preservative surgery? About 55 observations of
      splenic traumatisms, the authors compare advantages with drawback of each
      position and try to show out the factors acting on each choice to aim a
      preservative score the highest possible. Now the global preservative score is
      47%. The non operative proceeding lead 5/12 to failure. 10 preservative surgery
      initially performed lead to 10 success: preservative surgery, in our hands give
      the best results. Preservative surgery for a greater number of cases, and mainly
      for polytraumatisms (or multiple contusions) for which the collaboration of
      surgeons from different specialties make more difficult, for more stratified, the
      supervision in case of non operative proceeding.

PMID- 7729189
TI  - [Conservative surgery of the pancreas in complete traumatic sections of the
      Wirsung duct in children. Apropos of 2 cases].
AB  - A unanimous consensus has been achieved indicating the requirement of left
      pancreatectomy  after complete ruptures of the body of the pancreas in the child.
      Nevertheless, exeresis of the entire left part of the pancreas has severe long
      term consequences, especially if a small part of the gland is not left in place
      after the rupture. We report two cases of complete rupture of the isthma of the
      pancreas in two children who were treated by suture of the Wirsung and of the
      pancreas, followed by drainage. The drain dropped off early in both cases but did
      not hinder cicatrisation. Follow-up examinations were completely normal after a
      12-year follow up in the first case and after 10 months in the second.

PMID- 7729190
TI  - [The ECMES [Centro-Medullary Elastic Stabilising Wiring) osteosynthesis method in
      limb fractures in children. Principle, application on the femur. Apropos of 250
      fractures followed-up since 1979].
AB  - The theoretical basis of this new technique were recalled: a closed operation
      respecting the conjugation cartilages. The material, composed of flexible wires
      of adequate diameter are bent and stabilised forming a non traumatic fixation
      which is inserted into the medullary canal of the fractured bone under
      fluoroscopic surveillance. The second part of this paper deals with the results
      of 250 fractures of the femur followed up since 1979. Late outcome in terms of
      complications and stimulation of the post-trauma growth, which is a problem in
      all forms of fractures in the child, especially of the femur, is presented.

PMID- 7729191
TI  - [Modified subcutaneous mastectomy. Apropos of 916 cases].
AB  - Modified subcutaneous mastectomy was described by one of us in 1968; its
      approach, the dissection of the gland, plastic reconstruction of shape and volume
      are completely different from the subcutaneous mastectomy performed by plastic
      surgeons. 3 different time periods were studied to explain clearly evolution in
      the technic and indications. During many years retrospective studies made it
      possible to build a procedure according to the new diagnostic means for
      infraclinical breast cancer and to the constant improving prosthetic material.
      Therefore our indications for modified subcutaneous mastectomy are as following:
      suspicious mastopathies are the best indications with a performing choice of the
      radiologic images which require histologic control some evolutive or evoluated
      mastopathies some small infiltrating tumors developing in a highly dystrophic
      glandular surrounding. The numerous in situ cancers accompanying them argue for
      this choice. some big phyllod tumors or phyllod's recurrences.

PMID- 7729192
TI  - [Surgical approach to the dorsal section of the liver].
AB  - The dorsal sector of the liver is a deep and posterior territory which lies
      behind the hilum, close to the inferior vena cava, beneath a plane passing by the
      terminal portion of the main hepatic veins. Two segments may be distinguished. A
      left one, segment I, the prominent part of which is the caudate lobe, is united
      anteriorly with segment IV and lies to the left of the vena cava. A right one,
      segment IX, is posterior to the right portal pedicle, anterior to the vena cava
      (at times also to the right), beneath the terminal portion of the right superior
      and the middle hepatic veins. This dorsal sector is supplied by numerous small
      ascending portal branches of 1st, IInd and IIIrd order, and efferent veins enter
      directly the caval stem. The sector lies in the posterior surface of the liver,
      covered by the mass of the organ and the lesser omentum, fixed posteriorly by the
      coronary ligament and the entrance of the hepatic veins into the vena cava.
      However there is always a loose connective tissue between the liver and the vein.
      Three manoeuvres give access to this dorsal territory: 1. Posterior detachment of
      the liver by division of the lesser omentum, the falciform and coronary
      ligaments; the vena cava is then well exposed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729193
TI  - [Treatment of inguinal hernia by the endoscopic approach. Pre-peritoneal
      prosthesis. Apropos of 100 cases (with presentation of a video film].
AB  - Currently 500,000 inguinal herniorrhaphies are performed annually in United
      States. Most surgeons approach the inguinal region anteriorly. Very few surgeons
      use the posterior approach. Cheatle in 1920 followed by Nyhus in 1960, described
      the preperitoneal hernia repair. The preperitoneal approach has been used for
      recurrent hernias and for complicated hernias. In 1975, Stoppa added the use of a
      prosthetic mesh to the preperitoneal herniorrhaphy to improve the recurrence rate
      (1.4%). In the past few years, laparoscopy has replaced the traditional open
      technique in certain general surgical procedures (cholecystectomy, appendectomy).
      In this article, we will show that laparoscopic hernia repair is a viable
      alternative to the open herniorrhaphy because it combines the use of a proven
      method (preperitoneal prosthetic hernia repair) and the advantages of laparoscopy
      (less pain, fast recovery, better cosmesis).

PMID- 7729194
TI  - [Nasal reconstruction by frontal flaps].
AB  - A series of 51 nasal reconstructions using diverse forehead flaps is reviewed:
      the authors report their experience as well as the choices they made among
      various reconstructive procedures. 6 forehead flaps were selected in anticipation
      of solving most of the cases. The technical procedures devoted to the
      reconstruction of the inner plane and osteocartilagenous support are discussed.
      The complications are reported. Evaluation of the aesthetic result is quite
      subjective and thus rather difficult to quantify: limited defects give rather
      good results whereas more extended amputations such as those reaching the maxilla
      do not give accurate results.

PMID- 7729195
TI  - [Treatment of portal hypertension].
AB  - Injection sclerotherapy is the mainstay of treatment for acute variceal bleeding
      and for long-term management after a variceal bleed in 1993. However, the new
      technique of oesophageal variceal ligation may prove to be superior, either alone
      or in combination with low dose sclerotherapy. Pharmacological therapy for acute
      variceal bleeding is widely used and somatostatin appears to be the most
      effective agent. Long-term pharmacological therapy with beta-blockade is becoming
      increasingly accepted and some centres even use it as the primary therapy instead
      of sclerotherapy. Surgical shunts and major devascularization and transection
      procedures are mostly reserved for the failures of sclerotherapy, although
      certain groups utilize the Warren distal splenorenal shunt for the majority of
      fitter patients. Shunting may well prove to be more effective in long-term
      management than extensive devascularization and transection operations. The new
      interventional radiological technique, TIPS, is an exciting alternative procedure
      but it is unlikely to be accepted for widespread use because of increasing
      reports of encephalopathy and of late occlusion due to neointimal hyperplasia.
      TIPS's main role is as a bridge to transplantation for the failures of
      sclerotherapy oesophageal variceal banding.

PMID- 7729196
TI  - [Retrospective comparative study of 600 appendectomies carried out by laparotomy
      (Mac Burney) or laparoscopy. A plea for laparoscopy].
AB  - The authors report the results of a retrospective study comparing 305
      appendectomies by laparotomy (performed in 1988-1989) with 295 appendectomies by
      laparoscopy (1990-1991). The appendectomy was performed by the "out" technic in
      98% of cases of laparoscopy. The two populations are similar. There was no
      mortality. There was 1% of conversion, 1.4% of incidents and no major accident
      after laparoscopy. The post-operative course was smooth in 88.2% of cases after
      laparotomy and in 98% after laparoscopy. A treatment for pain was necessary in
      98% of cases after laparotomy and only 45.4% after laparoscopy. The rates of
      parietal complications, intra-abdominal complications and reinterventions were
      respectively 10.8%, 1% and 2.4% after laparotomy and 0%, 2.4% and 2.4% after
      laparoscopy. The mean hospital stay was 7 days after laparotomy and 4 days after
      laparoscopy. In conclusion, laparoscopy appears superior to laparotomy for
      performance of an appendectomy: it allows better abdominal exploration, more
      simple and shorter post-operative course and suppresses parietal complications
      provided that it is performed by a surgeon with great experience of laparoscopy
      and respects classic principles of digestive surgery.

PMID- 7729197
TI  - [Anastomotic aneurysm following insertion of aorto-iliac or aorto-femoral
      prosthesis. Treatment and long-term results].
AB  - This retrospective study was conducted to evaluate the long-term results obtained
      after treating anastomotic false aneurysm occurring after implantations of aorto
      iliac or aorto-femoral prostheses in order to identify optimal treatment. During
      a 20-year period, 66 anastomotic aneurysms were discovered and treated in 48
      patients. The mean delay after initial surgery was 6.3 years. Locations observed
      were femoral (n = 58) aortic (n = 6) and iliac (n = 2). Five aneurysms were
      revealed by an acute ischaemia, three others by bleeding and one by abdominal
      pain. The 57 others were diagnosed in an equal proportion either during physical
      examination or periodic imaging. Aortic and iliac aneurysms were treated by
      complete or partial replacement of the prosthesis. There were two urinary
      fistulas, one being fatal and one recurrent haemorrhage followed by death.
      Femoral aneurysms were treated in 4 out of 5 cases by interpositioning a
      prosthesis and in 1 out of 5 cases by simple resuturing. There was one fatal
      cerebral haemorrhage, 4 cases of early thrombosis and 6 cases, of recurrent
      anastomotic aneurysm (10%). The clinical course required amputation in 3
      patients. In this series, the overall outcome was satisfactory. For aneurysms of
      aortic or iliac anastomoses, one must avoid dissecting the prosthesis-ureter
      crossover and blind extraction of a branch which can lead to urinary fistulas.
      For femoral anastomoses, the following recommendations are important:
      conservation of the collaterals, suturing deeply into healthy tissue and
      interposition of a new prosthesis in case of tension. Cases of recurrent aneurysm
      are rare and should be treated with the same careful procedures.

PMID- 7729198
TI  - [Value of parathyroid scintigraphy in preoperative localization of parathyroid
      adenoma. Study apropos of 138 tests].
AB  - The authors have studied, about a total of 138 exams, the value of parathyroid
      nuclide scan. All the patients, who had primary hyper parathyroidism, have been
      operated upon. The results of parathyroid scintigraphy have been compared to the
      results of surgical exploration. Overall sensibility of the exam has been 80%,
      better with the MIBI (89%) than with the Thallium (78%). The specificity has also
      been better with the MIBI (95%) than with the Thallium (87%) with a global result
      of 88%). Computerized treatment of images with automatized subtraction especially
      studied in Institut Jean-Godinot, Rheims, explain the quality of these results.

PMID- 7729199
TI  - [Surgical treatment of chronic idiopathic constipation].
AB  - We review current experience with surgical treatment of severe constipation due
      to primary inertia of the colon. Over the last 10 years, we have operated 18
      patients (14 females and 4 males) with severe constipation. The surgical
      procedure was either nearly total colonectomy with ascending colon/rectum
      anastomosis (8 cases) or total colonectomy with ileorectal anastomosis (9 cases).
      In one patient, coloproctectomy was performed with an ileoanal anastomosi.
      Indications for surgery were based on results of barium emena and functional
      evaluation of defecation. Results were satisfactory in all patients. In several
      patients however, we noted that the motility of other levels of the digestive
      tract was also impaired. Colonectomy was introduced as a treatment for chronic
      constipation nearly a century ago and although very few indications have been
      retained in the recent this procedure has now become an acceptable surgical
      approach in a limited number of well-though-out cases.

PMID- 7729200
TI  - [Isolated severe anterolateral scapho-trapezo-trapezoid luxation. Diagnosis and
      surgical treatment in four cases].
AB  - Isolated injuries of the scapho-trapezial ligament complex are not well
      recognized. The ligament complex comprises the stout scapho-trapezial ligament,
      the floor of the flexor carpi radialis (FCR) tendon sheath and the scapho
      capitate ligament. Between August 1991 and May 1992, we diagnosed and treated
      four cases of partial chronic post-traumatic lesions of this ligament complex.
      There was chronic pain at the base of the thenar eminence and instability of the
      thumb-index-middle finger pinch. Standard X-rays were normal. The diagnosis of
      ligament rupture was confirmed by mid-carpal arthrography showing filling of the
      sheath of FCR tendon. Surgical exploration showed complete rupture of the tendon
      sheath of FCR in two cases, associated in the other two cases with complete
      rupture of the scaphotrapezial ligament. Direct repair of the ligamentous
      elements was performed in all cases. The tendon of FCR was sutured to the
      tubercle of scaphoid to protect and to reinforce the ligament repair. The
      patients have been followed-up for between 6 and 12 months. All four patients
      recovered normal pinch strength to the middle finger. One patient suffered from
      chronic pain at work.

PMID- 7729201
TI  - [Surgery of the pudendal nerve in various types of perineal pain: course and
      results].
AB  - In 1989, we reported our thoughts on the neurophysiological and anatomic aspects
      of pudendal nerve involvement in certain types of perinal pain. Since that time,
      the surgical approach has been modified. Here we report our follow-up of 40
      patients with 48 operated nerves. Follow-up ranged from 6 months to 7 years and
      outcome revealed improvement in 67% and no change in 33%. Thus surgery had been
      useful in two-thirds of the cases; in 44% of the patients, there was either a
      frank improvement or no change. Early diagnosis appears to be the determining
      factor in improving results. Operating for the canal syndrome must be performed
      before lesions to the nervous trunk become too important.

PMID- 7729202
TI  - [Surgery 93 in Vanuatu].

PMID- 7729203
TI  - [Reoperations on the renal artery].
AB  - Twenty six reoperations on the renal artery were performed upon 19 patients. This
      represents a 3.6% rate of repeat surgery in the author's series of renal artery
      repairs. The lesions requiring surgery were 22 repeat stenoses and 4 aneurysms of
      saphenous vein grafts. The 26 reoperations ended with nephrectomy in 8 cases and
      repeat repair in 18 cases. The nephrectomies were performed because of major
      difficulties for a repeat repair. The repairs were performed by conventional
      surgery in 9 cases and ex situ surgery in 9 cases. One postoperative death
      occurred (5.2%). Early thrombosis of segmental branches occurred in one patient
      requiring secondary nephrectomy. Late thrombosis of the repair occurred in one
      case in spite of normal patency of the repair on early postoperative angiography,
      and did not require any further surgery. Three repeat stenoses occurred (15.7%):
      one was not reoperated, the two others underwent one nephrectomy and one repair.
      On the whole, 12 long term successes out of 18 repeat repairs were obtained
      (66.6%). The results of successful repairs on renal function and blood pressure
      control are similar to those of primary repairs. Two reasons explain late
      alterations of initially satisfactory repairs: in only 3 cases (15.7%) worsening
      of atherosclerosis was responsible for repeat stenoses; in the majority of cases
      (16 out of 19, i.e. 84.3%), late alterations of the repair or of the arterial
      substitute occurred. The former lesions are unavoidable, the occurrence of the
      latter may be prevented by adequate surgical tactics or technique of the primary
      operation.

PMID- 7729204
TI  - [Therapeutic development in common bile duct lithiasis. Apropos of a 25-year
      experience].
AB  - Authors' experience in the treatment of common bile duct stones (LVBP), including
      592, operated patients, is presented. During the years 1969-1983, the most used
      technique was transduodenal sphincterotomy, while after 1983 choledocotomy,
      mostly with associated external temporary biliary drainage, was the preferred
      one. Since 1985 endoscopic sphincterotomy (SE) has been used, firstly for high
      risk patients, and then with increasing indications; at present the first choice
      in treatment of LVBP consists in sequential SE and laparoscopic cholecystectomy.
      Postoperative results of these techniques showed a specific mortality rate of
      1.1% for ST, of 0% for CT and SE, and a specific morbidity rate of 4.6% for ST,
      of 6.9% for CT and of 5.6% for SE. At follow-up patients in I and II Visick group
      were 87% for ST, 91% for CT and 100% for SE. Even if a statistical analysis of
      such results is not proposable, the only existence of a specific mortality for ST
      made us to change our choice. At present the treatment of choice for LVBP is in
      our opinion the sequential SE and laparoscopic cholecystectomy, waiting for a
      complete evaluation of all laparoscopic procedure. Traditional surgery is now
      indicated for failures of sequential approach and, as a first choice, for
      treatment of "empierrement" of common bile duct, for intrahepatic lithiasis and
      for atonic megacholedocus.

PMID- 7729205
TI  - [5-year survival after subtotal extensive esophagectomy for cancer].
AB  - Over a seven year period, subtotal esophagectomy for cancer was performed on 125
      patients (79.6% of the referred patients). Resection was potentially curative in
      92, and it was palliative in 33. Potentially curative esophagectomies were
      carried out either by right thoracotomy, cervicotomy and laparotomy (n = 77), by
      combined transhiatal and transcervical approach without formal thoracotomy (n =
      14), or by median sternotomy, cervicotomy and laparotomy (n = 1) depending on the
      tumor location in the esophagus and the general status of the patient. It
      included resection of the esophagus itself, and the lymph nodes and adjacent soft
      tissues located in the posterior mediastinum from the apex of the chest down to
      the diaphragm in patients operated on by right thoracotomy, in the posterior
      inferior mediastinum from the pulmonary veins down to the hiatus in those
      operated on by a transhiatal approach, and in the upper and lower mediastinum in
      those operated on transsternally. Twenty-eight patients operated on by
      potentially curative esophagectomy were given adjuvant radiotherapy or
      radiochemotherapy. Thirty-day and in-hospital postoperative mortalities were 0
      and 2.4% (3/125), respectively. Five-year actuarial survival was 30% in the whole
      series, and 41% after potentially curative resection. In the latter instance, it
      was 48% for adenocarcinomas v.s. 38% for squamous cell carcinomas (p > 0.05), 38%
      after transthoracic resection v.s. 61% after transhiatal resection (p > 0.05),
      44% after surgery alone v.s. 38% after surgery plus adjuvant therapy (p >
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729206
TI  - [Contribution and limitations of peroperative radiotherapy combined with excision
      curettage in the treatment of gastric cancers].
AB  - Macro- or microscopic residual tumor after surgery is the dominating prognostic
      factor in the treatment of gastric cancer. The majority of patients die of local
      recurrence and peritoneal spread. Therefore, in addition to gastrectomy and
      extended lymphadectomy (compartments 1 & 2) in some centers a adjuvant
      intraoperative radiotherapy is performed. Recent results of adjuvant
      intraoperative radiotherapy for gastric cancer revealed a lower local recurrence
      but there was no improvement in the survival rate for advanced tumor stages.
      These results are confirmed by our prospective study including 36 patients till
      now: in the group of 21 survivors there is no sign of a local recurrence. In 15
      patients which died meanwhile there was only one case of local recurrence (median
      follow-up: 9 months, range 1-30 months). Peritoneal spread and liver metastasis
      were observed as the most frequent cause of death (tumor stage IIIB and IV only).

PMID- 7729207
TI  - [Comparative study of results of hepatic transplantation between 2 groups of
      patients: alcoholic cirrhosis versus non-alcoholic cirrhosis].
AB  - Among the patients treated for alcoholic cirrhosis, only a small group could be
      candidates for liver transplantation (LT). The aim of this multicentric study was
      to analyse the results of LT in a group of 75 patients with alcoholic cirrhosis
      (AC) compared with a group of 61 patients with non-alcoholic cirrhosis (NAC).
      Results were similar in both groups concerning survival rate and quality of life.
      However the ability to go back to a normal professional life was less in the AC
      group. The reported recurrence of alcoholic intoxication, which was around 26%,
      was much lower for patients who interrupted alcohol consumption during at least 3
      months before L.T.

PMID- 7729208
TI  - [Immediate use of an expander during mastectomy. Analysis of 120 cases].
AB  - This study analyses a series of 116 patients, in whom mastectomy was followed by
      immediate insertion of temporary tissue expander. The technique is safe, simple
      and quick. It carries an acceptably low complication rate. Moreover, it does not
      interfere with any other local or general adjuvant therapy, if needed. The
      advantages are rapid post operative healing and psychological recovery, creation
      of a favorable site for a better quality breast reconstruction. Later on, any
      procedure for the breast reconstruction can be used. We concluded, that this
      procedure may be recommended more often; 62% of cases of mastectomies in this
      series.

PMID- 7729209
TI  - [A promising alternative for the treatment of type I diabetes. The implantable
      insulin pump].
AB  - Recent improvements in miniaturization of implantable pumps and the ability of
      their control by tele transmission allowed implantation of autonomous pumps which
      administer insulin into the peritoneal cavity. Fifty-six patients with diabetes
      mellitus underwent implantation of 66 pumps with a mean function life of 21.8
      months per patient. No patient died to this day. Tolerance of implanted
      components was good. Morbidity was limited to local events, in this series 4
      cutaneous erosions, two of them dictating final pump explantation. Dosages of
      mean global blood-sugar, pre- and post-prandial blood-sugar, and glycosylated
      hemoglobin were all lower versus dosages before implantation. Statistically
      significant difference was demonstrated regarding mean global blood-sugar.
      Frequency of sever hypoglycemia incidents (4 in our series) and of biological
      hypoglycemia (blood-sugar < 65 mg/100 ml) was decreased, representing major
      benefit of the technique. The patients well-being and quality of life were
      notably amended. Implantable insulin-pump may be offered as a treatment
      alternative to conventional insulin-therapy, especially in cases of diabetes
      which are difficult to balance and particularly in cases with frequent
      hypoglycemic malaise.

PMID- 7729210
TI  - [Comparison of treatment techniques of rhizarthrosis of the thumb. Apropos of a
      series of 98 cases].
AB  - We compared 3 methods of treatment of trapezometacarpal arthritis: partial
      trapezectomy with Ashworth Blatt interposition and total trapezectomy with either
      Swanson spacer or anchovy procedure. Out of a series of 85 patients (98
      operations), 52 (62 operations) were reviewed by an independent observer after a
      mean follow-up of 5 years. Silicone spacers were frequently complicated by
      subluxation, fragmentation and silicone synovitis. All procedures were effective
      on pain and mobility. Best results on strength were observed after trapezectomy
      with anchovy interposition and ligamentoplasty.

PMID- 7729211
TI  - [Acute dissection of the ascending aorta. Can the risk of reoperation be
      reduced?].
AB  - From January 1974 to October 1993, we operated 113 Stanford type A acute
      dissections of the ascending aorta. There were 19 cases of immediate death but
      overall mortality was low (17%). During the last 10 years, mortality was reduced
      to 12%. There were 94 survivors who were followed for 2 months to 19.2 years.
      Mean follow-up was 6.6 +/- 4.77 years. Total follow-up time was 583
      patients/years. There were 21 secondary deaths occurring within 2 months of
      surgery and the 10th post-operative year. Actuarial survival rate, including
      operative mortality, was 80 +/- 3.7% at 1 year, 70 +/- 4.6% at 5 years and 53 +/-
      6% at 10 years. There were 17 vascular complications during the follow-up
      including 12 requiring reoperation. There were no vascular complications in 90%
      of the patients at 3 years, 78% at 6 years and 60% at 10 years. Three cases of
      aortic insufficiency developed subsequently and required reoperation with
      prosthetic valve replacement. Operative techniques changed between the first and
      second decade of this series. During the second decade, cardioplegic protection
      of the myocardium, open distal anastomosis, systematic exploration of the aortic
      arch and finally extension of the resection to the isthmus when required were
      introduced successively. In the absence of sufficient follow-up in the patients
      operated during the second decade, it is not possible to establish whether these
      modifications have actually reduced the number of post-operative vascular
      complications commonly reported.

PMID- 7729212
TI  - [Arthroscopic treatment of anterior instabilities of the shoulder].

PMID- 7729213
TI  - [Conservative treatment of pancreatic injuries in children. Apropos of the
      communication of J. Prevot et al. Meeting of 13 October 1993].

PMID- 7729214
TI  - [Free transfer in emergencies for treating complex injuries. Apropos of the
      communication of E. Auclair et al. Meeting of 3 November 1993].

PMID- 7729215
TI  - [Growth cartilage in rabbits. Culture and cryopreservation].
AB  - Growth cartilage were cultured in order to determine whether cartilage growth
      could replace bone loss and generate autologous bone capable of further growth.
      An abundant quantity of mature functional chondrocytes is required after culture.
      Chondrocytes were isolated from a cartilage fragment by enzyme digestion.
      Trypsin, then collagenase were used as a function of the number of chondrocytes
      obtained per gram of growth cartilage. The optimal culture conditions were
      determined on the basis of three parameters: the density of cell seeding and the
      type and composition of the culture medium. The kinetics of chondrocyte growth
      and their fixation on different support media as well as their functional
      capacity was determined in different media according to the following conditions:
      seeding at 200,000 or 300,000 chondrocytes/cm2 on type 1 collagen and in Hamm-F12
      medium without supplementation with growth factors. The first trials of
      cryopreservation of the chondrocytes after culture gave promising results.
      Yields, expressed as the percentage of viable cells varied from 91 to 98%
      depending on the cryoprotective solution used.

PMID- 7729216
TI  - [Optimal conditions of gamma type irradiation for inactivating HIV in bone
      fragments. Consequences in biomechanical resistance of the bone tissue].
AB  - In order to determine bone-dependent penetration differences, we conducted a
      dosimetric study of gamma radiation using 2.5 mega rads on cancellous bone
      fragments at 4 degrees C and below 0 degrees with or without a surrounding
      solution. Variations in dose received inside and outside the femoral head were
      independent of radiation temperature but varied with the presence or absence of a
      surrounding solution. We then verified the gamma radiation effect on femoral
      heads infected with HIV: as free virus and in chronically infected cells. we
      evaluated infectious capacity after radiation by visualizing syncitia formation
      and by reverse transcriptase assay. The results for the controls were negative
      for free virus and positive for chronically infected cells. The virus was still
      after radiation. At the same time, we studied the effect of gamma radiation at
      different doses (0, 2.5, 5 mega rads) on biomechanical characteristics of bone,
      particularly crush resistance. Statistical analysis of the compression curves
      showed that resistance declined after high radiation at 5 mega rads, but the mean
      values obtained were within the range of values commonly accepted for human bone
      crush resistance.

PMID- 7729217
TI  - [Laparoscopic treatment of gastroesophageal reflux. Cardiopexia with the round
      ligament versus Nissen's type fundoplication].
AB  - Thirty nine patients with a symptomatic gastrooesophageal reflux (RGO), resistant
      to or relapsing after medical treatment, were prospectively studied and operated
      on with a laparoscopic approach: 8 which a ligamentum teres cardiopexy, 31 with a
      360 degrees fundoplicature. Both groups were comparable concerning clinical,
      endoscopic, mano- and pHmetric features (Anova test at 95% for all comparison in
      the study). There was no operative mortality. Conversion and morbidity rate were
      significantly higher (p = 0.04) in the "cardiopexy" group, even if data suggest a
      responsibility of the learning curve only. During follow-up patients were
      interviewed at 1, 3 and 12 months and proposed for mano- and pHmetry at 3 and 12
      months. Late results at 12 months showed a relapse of RGO in 5 out of 8 patients
      of the "cardiopexy" group, with no relapse in "fundoplicature" group (p = 0.01).
      Mano- and pHmetric records showed at 3 months a persistent hypotony of the lower
      oesophageal sphincter and a persistent acid reflux in the "cardiopexy" group,
      with a significant (p = 0.01 and = 0.03) difference with "fundoplicature" group,
      in which lower oesophageal sphincter was hypercorrected and no reflux appeared at
      pHmetry. Despite some rare evidence in literature, cardiopexy do not give good
      late results, and laparoscopic 360 degrees fundoplicature seems to be the better
      procedure for surgical treatment of symptomatic RGO.

PMID- 7729218
TI  - [Anus abscess. Value of systematic search of cases involving the primary orifice.
      Apropos of a series of 235 patients].
AB  - Based on our experience with 235 patients we emphasize the importance of
      examining, in the acute phase, the cryptic orifice and the trajectory of the
      fistula when treating anal abscesses. Fistulotomy can then performed in one or
      two operations. In specialized units, this attitude can give favourable results
      in nearly three-fourths of the cases and would avoid a large percentage of
      recurrent cases of suppuration.

PMID- 7729219
TI  - [Plea for a unifying concept of the cavernous sinus and the trigeminal cavity].
AB  - The object of this study is a scientific research in human and compared anatomy
      of the cavernous sinus and Meckel's cave. The observations made in the foetus and
      human adult are compared to these made in non human primates and domestic
      mammals, the cavernous sinus and the Meckel's cave contribute to realize a
      entirety that we call "a morphological and functional anatomical system". The
      human cavernous sinus and Meckel's cave are described as an indissociable
      parasellar space representing a heavy traffic area for vascular and nervous
      structures. In the human and non human primates, the authors observe a parasellar
      space which agreed with the concept of "trigeminal-cavernous anatomical system".
      In the cat, the same observations are made and an osseous outline closing the
      roof of the parasellar space is observed; this is the evidence of a more ancient
      osseous or cartilaginous wall. The authors demonstrate in the last part of this
      study that the morphogenesis of this trigeminal-cavernous system is in relation
      with the phylogenic development of its morphological and functional environment,
      that we call the "externation". This study is of interest: to a best
      understanding of the tumors involving the cavernous sinus, to a semantic point of
      view: an attempt to a review of the terminology applied to the cavernous sinus
      and Meckel's cave.

PMID- 7729220
TI  - [Bone resection-reconstruction of the diaphyseal zone in animals. Development of
      an experimental model, application to the study of biomaterials compared with
      allografts].
AB  - The aim of this work was to develop an animal model of bony resection
      reconstruction of the diaphyseal zone and to test the different bone substitutes
      in comparison with allografts. Eighteen 2-cm diaphyseal resections of the femur
      were performed in Beagle dogs. Reconstruction was performed using a bone
      substitute (5 cryopreserved allografts, 5 blocks of polymethylmetracylate with
      PMH hydroxyapatite, 8 blocks of phosphocalcium ceramic materials with biphased
      macropores) associated with centromedullar lockek nail. The PMH blocks gave
      radiographically and histologically unsatisfactory results. Allografts
      consolidated in two-thirds of the junctions, consolidating with an exuberant
      periosteal callus contrasting with minimal intracortical repair. No stress
      fractures were observed despite normal activity. BCP blocks consolidated in three
      fourths of the junctions but pseudoarthrosis at the centre of the block was
      observed in cases in which the fixation was not perfectly stable. Bone occupied
      20 and 24% of the surface of the ceramic block in the central and junctional
      zones respectively. These findings demonstrated the reliability of internal
      fixation material in the animal model and allowed us to evaluate the different
      methods for analysing bone repair on histographic and microradiographic images.
      In addition, the potential of synthetic material such as MBC might be useful in
      large resections in mechanically stressed zones.

PMID- 7729221
TI  - [The sheep: an animal model for ligament prostheses?].
AB  - Ruptures of the anterior cruciform ligament is difficult to repair. Ligament
      prostheses are sometimes useful. We tested a ligament prosthesis which had the
      original property of combining a polyester braid with a matrix favouring collagen
      ingrowth. We implanted this prosthesis in the knee joint of 10 sheep after
      sectioning the anterior cruciform ligament at it origin. The ligaments were
      recovered after 6 months. We studied the functional and radiographic results.
      Tolerance was studied in samples of the articular fluid and synovial tissue. We
      evaluated bone attachment and fibrous growth using micro-radiography and specific
      coloration techniques. Samples were examined under electron microscope. No
      rupture was encountered. We observed a satisfactory functional and radiographic
      result. No intolerance was observed. The neoligament had a bony or mixed
      attachment in 60% of the cases and was comprised of oriented tissue in 90% of the
      cases. Vascular invasion was important. These findings are promising and suggest
      that long-term studies should be undertaken.

PMID- 7729222
TI  - [Air pouch model in the rat for evaluating articular phlogogenic capacity of
      ceramics].
AB  - We used the joint air pouch model in rats to study the inflammation induced by
      three types of calcium phosphate biomaterial: 10 mg of synthetic hydroxyapatite
      (HA), a sintered ceramic made of hydrooxyapatite and phosphate tricalcium (BCP),
      and calcium phosphate in the form of a fibre extracted from a vitro-ceramic
      material (VPC). Histological examination was made after 48 hours. The most
      intense inflammatory reaction was observed with BCP: the thickness of the
      superficial stratified layer of synoviocyte-like cells doubled, interstitial
      fibrosis occurred and neovascularization with polymorphous inflammatory
      infiltration was seen. HA led to the same, though less intense, type of reaction.
      Discrete, variable, localized inflammation was seen with VPC and was limited to
      the areas where the calcium phosphate fibres rolled. Despite good bone tissue
      tolerance, intraarticularly, these biomaterials can lead to synovial
      inflammation. This phlogogenic action varies greatly depending on the
      microcrystals injected. The factors which might affect the joint inflammatory
      reaction, including the size and surface of the microcrystals, the crystallinity,
      pH and physical treatments (heat, compaction) should be further evaluated with
      precision.

PMID- 7729223
TI  - [Characterization of biomechanical behavior of the lumbosacral spine in dogs.
      Characteristics related to spondylosis and disk degeneration].
AB  - The in vitro and static biomechanical behaviour of vertebrae with spondylosis
      were compared with that of healthy vertebrae. In the dog, spondylosis
      predominates in the lombo-sacral spine which was chosen as an animal model for
      spontaneous spondylosis. Fourteen surgical specimens were take from German
      shepherd dogs which had been submitted to right and left lateral flexion,
      saggital flexion and dorsal flexion. Angular displacements were recorded with an
      analyser of spinal movement. Our results demonstrated diseased vertebrae have
      more flexibility than healthy vertebrae in the sagittal and frontal planes than
      but less so for dorsal flexion. In Addition, diseased vertebrae tend to move
      upward during lateral flexion. Exeresis of ligament and capsular structures has
      allowed us to demonstrate the importance of these structures in maintaining spine
      stability in the sagittal plane and in joint coaptation. Exeresis of the facet
      joints led to the demonstration of the role of these structures in the
      maintenance of spine stability in the transverse plane in cases of disc
      degeneration.

PMID- 7729224
TI  - [Intrafocal wire fixation of wrist fractures. The original Kapandji technique.
      Course. Review of 400 cases].
AB  - Dynamic intrafocal pin fixation, first described by Kapandji for extra-articular
      fractures is an elegant solution for consolidating wrist fractures with posterior
      compression. We reviewed our experience using this method with 400 patients,
      confirming the validity of the method when applied rigorously. Globally, there is
      a correlation between the radiological findings and the quality of the clinical
      results which were satisfactory in 90% of the cases analyzed. Indications now
      include many joint fractures as a three-pin intrafocal fixation is performed.
      There is also the risk of creating an associated anterior comminution (either by
      trauma or iatrogenic) causing inadapted calus formation by secondary impaction,
      often with severe affects on the lower radio-cubital area. To avoid this
      inconvenience, we propose aasociating pin fixation with anterior internal
      fixation by an anterior plate. Analyzing 50 cases seen after consolidation
      confirmed the importance of this complementary fixation. Thus multiple fixation
      maintains good joint alignment without final compression leading to the quality
      results obtained.

PMID- 7729225
TI  - [Paraganglioma of the organ of Zuckerkandl].
AB  - From the study of one case of non secreting paraganglioma of the organ of
      Zuckerkandl, the authors have surveyed the existing literature gathering 95 cases
      from 1902 to 1992. It is an exceptional tumor of the paraganglioma and it often a
      secreting one. When it is not it looks like a malignant retroperitoneal tumor.
      The surgical resection is often performed without the operating diagnosis.
      Asserting the malignancy of these tumors only depends on the presents of
      metastasis appearing lately. There fore a long continued control of the patients
      who have been operated upon is a must all the more as 30% of the paraganglioma of
      Zuckerkandl prove to be malignants.

PMID- 7729226
TI  - [Problems posed by secondary peritoneal carcinosis of digestive origin].
AB  - Secondary peritoneal carcinoma occurs in cases of malignant bowel disease after
      the initial curative operation or rarely after palliative surgery. The main
      problems are frequent overshoot in the diagnosis and correct management. Based on
      our experience with 101 patients with secondary peritoneal carcinoma treated over
      the last 10 years, we determined the therapeutic possibilities. In 23% of the
      cases no surgery was possible and in only 4% underwent a second palliative
      operation. Survival was basically dependent on the initial malignant disease.
      More aggressive therapeutic methods are currently under study.

PMID- 7729228
TI  - [Principles of endo-thoracic video-surgery and results in the treatment of
      spontaneous pneumothorax].

PMID- 7729227
TI  - [Quality of life and ileo-anal anastomosis with pouch. Results of a prospective
      series of 35 surgically treated cases of hemorrhagic rectocolitis. Proposal for a
      score of quality of life].
AB  - Ileal-pouch anal anastomosis (IPAA) following coloproctectomy avoids permanent
      ileostomy, and allows complete excision of diseased mucosa in ulcerative colitis
      (UC) and adenomatous polyposis. Preserving normal intestinal pattern, the goal of
      IPAA is to improve quality of life for patients. This study was designed to
      measure the impact of IPAA on quality of life in a series of 35 surgically
      treated UC. Four fields of quality of life were explored: diet, professional
      activity, sport practice, sexual activity. Interview with independent observer
      and prospective follow-up allowed to establish a score from 0 (excellent quality
      of life) to 19 (bad quality of life). In the same time, functional score
      evaluating pouch evacuation and continence was established (0 = excellent
      function, 30 = bad function) to be compared to quality of life. The series
      included 35 IPAA in function for more than 6 months (mean follow-up = 46 +/- 31
      months), performed for UC (14 females and 21 males, mean age: 34 y-a).
      Respectively 30 (86%) and 5 (14%) of the patients had an excellent and fair
      quality of life, according to the scoring system: 25 had no diet, all but one had
      a normal professional activity and all were satisfied of sport practice; 33 had
      no sexual disturbances related to IPAA, but 3 female patients complained of
      infertility. Functional results were excellent, fair and bad respectively in 25
      (72%), 9 (26%) and 1 patients: stool frequency was 4.6 +/- 2 per day, 60% of
      patients having no nocturnal emission, and 90% being able to delay for more than
      1 hour.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729229
TI  - [Video-assisted thoracic surgery. Current techniques and indications].
AB  - Up til recently, thoracoscopy was essentially performed for diagnostic purposes,
      allowing biopsies of the pleura or peripheral lesions of the lung tissue.
      Indications with a therapeutic objective were less frequent, usually in cases of
      recurrent pneumothorax. The recent development of less aggressive, more surgical
      instruments has virtually "forced" the surgeon to use the thoracoscope. Video
      thoracoscopy surgery thus entered the therapeutic armenatum. Small access
      channels less than a centimeter in diameter are used for videothoracoscopy giving
      an indirect view on the screed of the thoracic contents. Under these conditions,
      thoracoscopic procedures are possible to treat pneumothorax and resect small
      pleural or parenchymatous tumours. Inversely, gross resections (lobectomy,
      pneumonectomy) are technically more complex and raise the nearly unsolvable
      problem of removing the surgical specimen. In fact, a mini-thoracotomy has been
      required in many cases, leading to the development of video-assisted thoracic
      surgery. This new surgical technique is performed via a small incision and is
      guided by optic probes connected to the video screen. The surgeon can thus follow
      the entire operation both directly via the mini-thoracotomy and indirectly on the
      screen. This new approach is an interesting compromise between conventional
      thoracic surgery and videothoracoscopy.

PMID- 7729230
TI  - [Video-surgery and esophagus].

PMID- 7729231
TI  - [Interruption of the ductus arteriosus by video-surgery].

PMID- 7729232
TI  - [Endo-thoracic video-surgery. Where is the real progress?].

PMID- 7729233
TI  - [Persistent and recurrent primary hyperparathyroidism].
AB  - Aim of this study is to evaluate clinical, radiological and therapeutic aspects
      of patients who have persistent or recurrent primary hyperparathyroidism. First,
      it is essential to reconfirm the diagnosis. Then, the previous operative and
      pathology reports must be reviewed. In these patients, it is important to use
      preoperative localization studies. When the results of the various localization
      tests were combined, the site of the elusive remaining parathyroid tumor could be
      identified in more than 80%, enabling a focused surgical approach which not only
      saves time, but also improves the success rate and decreases morbidity.
      Cryopreservation and autotransplantation are commonly used.

PMID- 7729234
TI  - [Blunt injuries of the spleen. What is the role of splenectomy?].
AB  - In an exhaustive retrospective study of splenic trauma diagnosed over a 7-year
      period (1986-1992) in our orthopaedic trauma centre we collected 63 cases.
      Splenectomy was performed in 25 patients, conservative surgery was performed in 6
      and non-surgical conservative therapy was possible in 32. The large percentage of
      non-surgical cases was possible due to the simple clinical course in cases
      diagnosed late and because of careful surveillance and the precision of
      scanographic diagnosis. The concept of conservative non-surgical treatment
      appears to be validated by the lack of mortality and the high success rate (only
      3 failures out of 32) in our unselected population which included polytrauma
      cases and patients of all ages and all types of splenic lesions. Nevertheless,
      shock resulting from splenic injury. In cases where bleeding is the sign of non
      surgical treatment failure and in cases with acquired or induced coagulopathy and
      a pathological spleen, splenectomy is also indicated. Our results indicate that,
      when scanographic diagnosis is permanently available and when clinical
      surveillance is adequate, conservative non-surgical treatment can be proposed in
      patients with a stable haemodynamic status.

PMID- 7729235
TI  - [Anatomical bases of operative lesions of the musculocutaneous nerve in surgery
      of the shoulder].
AB  - The operative management by coracoid graft transfers in the recurrent
      dislocations of the shoulder and the frequent shoulder arthroscopies could be the
      source of lesions to the musculocutaneous nerve. Although rarely mentioned in
      articles, these complications certainly exist. The precise topography of this
      nerve does not seem to be well known by surgeons. Consequently, we returned to
      the anatomic study of the nerve with its variations and their relationship to the
      external terminal anomalies of the brachial plexus.

PMID- 7729236
TI  - Subjective time scaling: influence of age, gender, and Type A and Type B
      behavior.
AB  - Forty-eight subjects, divided into 4 equal groups (young and older female, young
      and older male), reproduced 19 time intervals varying in logarithmic steps
      between 1.3 and 20 s. The durations were indicated by noise of 50 dB SL. To
      assess Type A and Type B behavior, the subjects were administered a Swedish
      version of Jenkins Activity Survey with 21 items. It was found that 1.
      reproductions of durations by older subjects are longer than those by younger
      subjects, and 2. reproductions by male subjects are shorter than those by female,
      although an interaction was also detected between gender and the standard
      durations. Type A and Type B behavior did not show any main effect. The data were
      treated in accordance with the "parallel-clock model", whereby the parameters of
      the psychophysical power function are determined from duration reproduction data.
      As in previous experiments, the data showed a break in the function, entailing
      two segments. The effect of both age and gender could be explained by the weight
      coefficient of the upper relative to the lower segment of the psychophysical
      function, the coefficient being lower for male and higher for older subjects.

PMID- 7729237
TI  - Time-dependent effects of ASA administration on blood pressure in healthy
      subjects.
AB  - Several studies aimed at testing the effects of low-dose acetylsalicylic acid
      treatment (ASA, aspirin) in the prevention of preeclampsia conclude that
      beneficial effects of such treatment outweigh adverse ones. Since recent results
      suggest that desired effects upon lipoperoxides and beta-adrenergic receptors are
      dependent on the circadian timing of ASA administration, we aim to study if ASA
      therapy can be optimized by timing according to the rest-activity cycle.
      Accordingly, before conducting clinical trials on pregnant women, we have
      examined in clinically healthy subjects the possibility that effects of ASA upon
      blood pressure could indeed be time-dependent. We studied 55 healthy subjects (35
      men and 20 women), 19-24 years of age (mean +/- SD: 20.9 +/- 1.8). Subjects were
      living on their usual diurnal waking (approximately 08:00 to approximately
      24:00), nocturnal resting routine during sampling, following every-day life
      conditions without any restriction. The systolic, mean arterial and diastolic
      blood pressures and heart rates of each subject were automatically monitored
      every 30 min. for 48 hrs with an ABPM-630 Colin (Komaki, Japan) device before and
      after a one-week course of aspirin (500 mg/day). Subjects were randomly assigned
      to one of three groups, according to the circadian timing of administration of
      the daily dose of ASA: within two hours of awakening (R x 1), seven to nine hours
      after awakening (R x 2), or within two hours before bedtime (R x 3). The second
      blood pressure profile was obtained during the sixth and seventh days of
      treatment (to avoid differences in activity dependent on the day of the week).
      Results indicate a statistically significant blood pressure reduction (negative
      mean area between the blood pressure profiles obtained before and after aspirin
      administration) only when ASA was given seven to nine hours after awakening (R x
      2; P = .012, .003, and .006 for systolic, mean arterial and diastolic blood
      pressure, respectively). These results were corroborated by a non-parametric
      (sign) test, also indicating the significant reduction in systolic and diastolic
      BP for R x 2 (P = .003 and .010, respectively). Non-invasive BP monitoring
      combined with the proper analysis of the time series thus obtained could then
      provide a cost-effective approach for testing the circadian optimization of long
      term ASA administration for both cardiovascular disease prophylaxis and
      prevention of preeclampsia.

PMID- 7729238
TI  - Heart rate and blood pressure chronomes during and after pregnancy.
AB  - Whereas conventional time-unspecified single measurements of blood pressure and
      heart rate may mislead, influenced as they are, among other factors, by the
      individual's emotional state, position, diet and external stimuli generally, the
      chronobiologic evaluation of predictable variability in these physiologic
      variables assesses early cardiovascular disease risk in pregnancy by (a) the use
      of fully ambulatory devices and (b) the proper processing of the time series thus
      obtained. We have used this approach to quantify changes in 24-h synchronized
      circadian characteristics of cardiovascular variables in two consecutive
      pregnancies of a clinically healthy woman. The results were then compared with
      those obtained from data sampled after the second pregnancy. Blood pressure and
      heart rate were automatically monitored, at 1-h intervals, each time for at least
      48 consecutive hours, and for a total of 76 days of monitoring in each pregnancy.
      Circadian parameters of those circulatory variables were computed for each 48-h
      profile of measurements by the least-squares fit of a 24-h cosine curve.
      Regression analysis of parameters thus obtained revealed patterns of variation of
      circadian rhythm-adjusted means and amplitudes with gestational age. In both
      pregnancies, the predictable variability of the circadian rhythm-adjusted mean of
      blood pressure can be approximated by a second-order polynomial model on
      gestational age: a steady linear decrease in systolic, mean arterial and
      diastolic blood pressures up to the 22nd week of pregnancy is followed by an
      increase up to the day of delivery. This pattern of variation is not found for
      data similarly sampled during non-pregnancy on the same woman. This longitudinal
      study confirms and extends to ambulatory everyday life conditions the predictable
      pregnancy-associated variability in blood pressure and heart rate and also allows
      the establishment of prediction and confidence limits for cardiovascular
      parameters in a healthy pregnancy.

PMID- 7729239
TI  - Biomedical pattern discrimination of neonatal cardiovascular risk.
AB  - Genetic risk is a primary contributing factor to the predisposition of a newborn
      child to elevated blood pressure later in life. An index for this factor is
      needed to assess in the neonate the success or failure of preventive
      interventions instituted for the pregnant woman. This index could be based on
      characteristics describing the variability of blood pressure and heart rate
      during the first days after birth. In the search for such an index, the systolic
      and diastolic blood pressures and heart rates of 150 newborn babies were
      automatically monitored at about 30-minute intervals for 48h with a Nippon Colin
      device, starting early after birth. On the basis of questionnaires given to the
      parents, the neonates were assigned to a group of either a negative or positive
      family history of high blood pressure, according to the absence or presence of
      high blood pressure and/or related cardiovascular disease in two generations
      (those of the newborn's parents and grandparents). Circadian characteristics and
      descriptive statistics for the three circulatory variables were used for
      classification by a so-called "monotest", an all-subsets variable selection
      technique for biomedical discriminant analysis. For a particular combination of
      variables, the "monotest" performs as many steps of separate analyses as the
      total number of subjects, each subject's data being compared as a set with those
      of all others ("leave-one-out" approach). When the circadian amplitude of
      systolic blood pressure was used as classifier, the "monotest" yielded a 63%
      classification equivalent to prior criteria, the latter being based on a negative
      or a positive family history of high blood pressure. The "monotest" complements
      rhythmometric procedures and defines a set of individualized criteria for risk
      assessment. The combined use of automatic hardware for time-specified sampling
      with proper software for signal processing and discriminant analysis allows to
      recognize parameters of blood pressure circadian variability as a source of
      information for neonatal classification according to cardiovascular disease risk.

PMID- 7729240
TI  - Ultradian-infradian variation of cardiac creatine phosphokinase (CPK) activity in
      male Holtzman rats.
AB  - Reference standards were sought for use in the search of any indications of
      myocardial damage by an alteration of the time structure, or chronome, of
      creatine phosphokinase (CPK) "MB" isoenzyme activity in the heart of the male
      Holtzman rat. 144 rats were kept on 6 lighting regimens staggered by 4 hours, 24
      rats per chamber. On 8 consecutive days, hearts from 3 animals from each chamber
      were harvested and weighed. The left ventricle was dissected, homogenized in a
      buffer solution at 4 degrees C and stored frozen at -20 degrees C until analysis.
      A supernatant aliquot of each sample was analyzed by a discontinuous gradient
      elution from DEAE-Shephadex A-50 columns. The CPK isoenzymes were quantified by
      the Rosalki method. Results of the CPK assay from each time point were analyzed
      by linear and nonlinear least-squares rhythmometry. Among other components, a
      168h or circaseptan rhythm characterized CPK activity in the heart of Holtzman
      rats. This component and other ultradian and circadian aspects of the time
      structure of rhythms and trends, the chronome of a given variable, may serve, by
      any eventual alteration of their dynamic characteristics, as gauges of potential
      cardiac damage prior to the occurrence of an increase in the overall mean of the
      enzymatic activity.

PMID- 7729241
TI  - Broad scope of a newly developed actometer in chronobiology, particularly
      chronocardiology.
AB  - The scope and the details of a newly developed actometer were introduced. We are
      able to select a desired threshold of gravity(g)-forces between 0.01g and 0.50g
      and to simultaneously monitor 3 kinds of activity along with an averaged g-force
      every minute. As a routine study, we monitored at settings of 0.01g, 0.05g and
      0.20g and averaged on one channel. Part of the time, physical activity was
      monitored together with ambulatorily monitored blood pressure (BP) and the ECG,
      or at least heart rate (HR). Physical activity showed a circasemiseptan and
      circaseptan periodicity as well as the circadian component, especially in
      subjects with an irregular sleep-wakefulness life style. On the average, physical
      activity was greater on a working day than on a holiday. Everyday physical
      activity reflects in part the ability to exercise, and it is expected that this
      actometer can contribute or provide an objective individualized quality-of-life
      index. The effect of physical activity on circadian profiles of BP, HR and HR
      variability is also examined. We observed that BP started to increase several
      hours before getting up. This fact likely shows that there is an endogenous
      circadian rhythm in BP, independently of the sleep-wakefulness cycle. Lastly, we
      investigated the relationship between physical activity and HR in patients
      permanently paced; we confirmed that the DDDR pacing mode was more physiological
      than the VVI or VVIR mode. This newly developed actometer will bring about
      further progress in chronobiology.

PMID- 7729242
TI  - Cross-spectral coherence between geomagnetic disturbance and human cardiovascular
      variables at non-societal frequencies.
AB  - A 35-year-old cardiologist monitored himself with an automatic ABPM-630 (Colin
      Electronics) monitor, mostly at 15-minute intervals around-the-clock for three
      years with a few interruptions. In this subject with a family history of high
      blood pressure and stroke, a cross-spectral analysis revealed a statistically
      significant coherence at 27.7 days between systolic and diastolic blood pressure
      and heart rate vs. the geomagnetic disturbance index, Kp. A lesser peak in
      coherence was found for systolic blood pressure with Kp at a trial period of 4.16
      days (P = 0.046). These results suggest that changes in geomagnetism may
      influence the human circulation, at least in the presence of familial
      cardiovascular disease risk, and they may do so at frequencies that have no
      precise human-made cyclic worldwide match.

PMID- 7729243
TI  - A local renin-angiotensin system in the human adrenal gland: evaluation of in
      vitro secretion by a non-parametric combination of randomness permutation tests.
AB  - The aim of this study is to assess the mode of release of renin, angiotensin II
      and aldosterone during in vitro superfusion of the human adrenal gland using a
      non-parametric combination of four randomness tests. Five normal adrenals and
      four aldosteronomas superfused over 270 mins were found to concomitantly release
      renin, angiotensin II and aldosterone. The pattern of this release exhibited a
      significantly non-random pulsatile character in 17 out of 23 single hormone
      series (p < 0.05). A further statistical combination-test analyzing the release
      of each hormone for all experiments with normal and pathological tissue,
      respectively, showed significant pulsatility (p < 0.01) in 5 out of 6 groups. The
      pulsatile mode of in vitro hormone release by the human adrenals indicates an
      active secretory process rather than a discharge of tissue-stored forms. The
      source of such intra-adrenal intrinsic pulse-generating mechanism could reflect
      the periodic course of a negative biological feedback reaction.

PMID- 7729244
TI  - Circadian rhythmic hepatic biliary flow, constituents, concentrations and
      excretory rates in patients after cholecystectomy.
AB  - Twelve adult patients with indwelling common bile duct T-tube were selected for
      the study of circadian fluctuation of biliary excretion. From the 10th
      postoperative day on when the enterohepatic circulation was well reestablished a
      5 ml bile sample was collected at the end of each 4-h interval for 3 to 4 days
      for determination of the concentrations of various biliary constituents. This was
      followed by measurement of bile flow rate by collecting the bile continuously
      through the T-tube at 4-h intervals for another 3 to 4 days. One quarter of the
      twelve patients showed no persistent daily fluctuation of all the variables
      studied. A circadian rhythm was demonstrated by single cosinor rhythmometry in
      the biliary concentrations of bile acid, cholesterol, phospholipid, bilirubin,
      alkaline phosphatase, and lactate dehydrogenase in the remaining nine patients.
      Among them six also showed a circadian fluctuation of hepatic bile flow. The lack
      of synchronization of the rhythm of the concentrations of various biliary
      constituents with the bile flow rate resulted in undetectability of a circadian
      rhythm for their excretory rate in the great majority of patients. Those few
      patients in whom a rhythm remained to be detectable had a much reduced amplitude
      but the same acrophase. We concluded that bile flow rate played a major role in
      the circadian rhythm of biliary excretion and might coordinate the fluctuation of
      the concentrations of various biliary constituents. However, a true circadian
      rhythm for their concentrations also existed at least in certain subjects.

PMID- 7729245
TI  - Circadian rhythmicity of interferon-gamma production in antigen-stimulated whole
      blood.
AB  - Recently, assessment of T cell function has been refined by the ability to
      measure cytokines produced by activated T cells. We developed a whole blood assay
      to detect antigen-activated T cells that produce IFN-gamma. With this assay we
      have found a large circadian variation in tetanus- (acrophase 00(00) p < 0.001)
      and PPD- (acrophase 00(08) p < 0.001) stimulated IFN-gamma production. IFN-gamma
      production is inversely correlated with plasma cortisol (r = -0.5), suggesting
      that variation in IFN-gamma production may be secondary to circadian variation in
      plasma cortisol levels (acrophase 11(06)). The demonstration of circadian
      rhythmicity in antigen-stimulated IFN-gamma production is relevant to the
      diagnostic use of whole blood assays and, in addition, may have implications for
      the therapy of immuno-inflammatory diseases.

PMID- 7729246
TI  - Circannual periodicities in the incidence of ulcerative colitis do persist in the
      era of chemotherapy.
AB  - A series of 274 attacks (256 of them recurring) of ulcerative colitis in 158
      subjects, observed between January 1974 and December 1990 in Bratislava (48
      degrees N, 17 degrees E), Slovakia, has been processed by R.A. Fisher's
      periodogram and F. Halberg's cosinor procedure. In spite of the long-term
      administration of sulfasalazin and/or corticosteroids, an unequivocal
      statistically significant (alpha = 0.01) annual (P = 0.0003) rhythmicity was
      identified. The amplitudes of both cycles were very similar, approximately 25% of
      the MESOR. The first estimated peak occurred in the second half of March and the
      first half of April, with an estimated increase of more than 50% over the average
      monthly incidence, resulting from coincident acrophases of both components. The
      second semiannual peak occurred at the end of September and early October. It is
      concluded that the long-term chemotherapy, applied in the majority of cases,
      failed to substantially influence the known circannual variations of the disease
      attacks. The issue has to be taken into account in planning prevention measures,
      treatment and its evaluation, as well as in organizing the regimen of management
      in endoscopic centers.

PMID- 7729247
TI  - Chrono-meta-analysis of circadian phagocytosis rhythms in blood of guinea pigs on
      two different lighting regimens.

PMID- 7729248
TI  - Further data and analyses.

PMID- 7729249
TI  - Statistical significance without biologic signification is not enough:
      illustrative example.

PMID- 7729250
TI  - Cardiovascular disease risk monitoring in the light of chronobioethics.

PMID- 7729251
TI  - "Cancer marker chronomes" assessed in the light of chronobioethics.

PMID- 7729252
TI  - In defense of proper cosinor analysis.
AB  - Parallaxes can originate from different sources, from bias towards proving a
      favored hypothesis, but also from bias against existing evidence in support of an
      unwanted hypothesis. One approach to avoiding either bias is to shift emphasis
      from hypothesis testing to parameter estimation. Complementary statistical
      approaches applied to replicates of given experiments can then serve to further a
      given field of science by providing converging or diverging results depending on
      whether the original hypothesis was true or false.

PMID- 7729253
TI  - Agostino Carandente.

PMID- 7729254
TI  - Dora K. (Holly) Hayes.

PMID- 7729255
TI  - Models for chronobiologic risk and prepathology detection. A tribute to Bill W.
      Kennedy.

PMID- 7729256
TI  - "Helicobacter heilmannii" infection in a patient with gastric cancer.

PMID- 7729257
TI  - Cecum of guinea pig is a reservoir and sigmoid is a high-resistance conduit.
AB  - We compared the filling responses of the cecum and the sigmoid of the guinea pig
      using volumes up to 60 ml and 2.5 ml, respectively. In the isolated cecum, each 1
      cm increment of hydrostatic pressure above zero led to accommodation of 10 ml
      volume; in the sigmoid, the yield pressure (at which accommodation first
      occurred) was 6 cm H2O, and pressure increments up to 20 cm H2O produced volume
      increments of less than 0.5 ml. Resting pressure at half-maximal filling was 5.0
      +/- 0.7 cm H2O for the sigmoid and 1.7 +/- 0.6 cm H2O for the cecum. K+
      depolarization led to a significant upward shift in the pressure curves of both
      segments. Ca2+ withdrawal decreased sigmoid and cecal pressures at some volumes.
      Distension of the cecum triggered intermittent contractions, which began with the
      shortening of the teniae and were associated with low-amplitude pressures and
      expulsion of a 5- to 10-ml volume. Distension of the sigmoid produced propagating
      contractions that were associated with high-amplitude pressures and lengthening;
      compartmentalization in the sigmoid prevented efflux from it, and volume inflow
      was not affected by pressure waves. Our observations indicate that its large
      capacity and great distensibility make the cecum suitable for reservoir
      functions, whereas its narrowness and lack of distensibility make the sigmoid a
      high-resistance conduit.

PMID- 7729258
TI  - Effects of enteral feedback inhibition on motility, luminal flow, and absorption
      of nutrients in proximal gut of minipigs.
AB  - We wanted to clarify whether the postprandial intestinal feedback control
      activated by nutrients in the distal gut exerts different effects on motility,
      transit of digesta, and absorption of nutrients in the proximal gut.
      Additionally, interrelationships among motility, transit, and absorption were to
      be elucidated because these relationships have only been investigated in the
      fasted state. In five minipigs, a 150-cm segment of the proximal jejunum was
      isolated by two cannulas. Motility of the jejunal segment was recorded by
      multiple strain gauges and analyzed by computerized methods. Markers (Cr- and Cu
      EDTA) were used for the measurement of the flow rate, transit time, and
      absorption of nutrients. After a meal, the test segment was perfused with 2
      kcal/min of an elemental diet over a period of 90 min. A feedback inhibition was
      activated by infusion of nutrients into the midgut at rates of 1-4 kcal/min.
      Saline was infused as control. With increasing energy loads infused into the
      midgut, the motility index and the length of contraction waves decreased, whereas
      the incidence of stationary contractions increased, ie, the motility changed from
      a propulsive to a segmenting pattern. These modulations of motility were
      associated with a linear decrease in the flow rate and a linear increase in
      transit time. Flow and transit were linearly correlated with each other.
      Additionally, the reduction in flow rate and the delay in luminal transit were
      associated with a linear increase in the absorption of nutrients. However, the
      increase in absorption induced by the feedback mechanism was small (7.3-13.4%)
      compared to the marked inhibition of the motility parameters (54-64%), the flow
      rate (59%), and the delay of transit (5.8-fold). Feedback control primarily
      modulated motor patterns and luminal flow, whereas the small increase in
      absorption was only a side effect due to the longer contact time of the nutrients
      with the mucosa.

PMID- 7729259
TI  - Postischemic intestinal motility in rat is inversely correlated to length of
      ischemia. An in vivo animal model.
AB  - An inverse correlation between postischemic gastrointestinal motility and the
      length of intestinal ischemia was found in an animal model. Intestinal ischemia
      was caused without concurrent laparotomy and for a predetermined time period
      (ischemia time) by pulling on an external nylon thread that was threaded through
      a double-lumen catheter. This catheter was passed into the abdominal cavity to
      encircle the superior mesenteric artery. Gastrointestinal motility was determined
      by the introduction of a color-marked meal into the animal's stomach and the
      measurement of the proportionate length of the small bowel filled with it
      (transit index). This simple and reliable animal model can also be used for the
      evaluation of techniques and pharmacological manipulations aimed at modulation of
      the effects of intestinal ischemia on intestinal motility and its consequences.

PMID- 7729260
TI  - Gastrointestinal bleeding and intestinal ischemia associated with anticardiolipin
      antibodies.

PMID- 7729261
TI  - Arterioportal fistula following liver biopsy. Three cases occurring in liver
      transplant recipients.
AB  - Although liver biopsy is a very useful procedure used frequently in the diagnosis
      and management of liver dysfunction occurring after orthotopic liver
      transplantation, complications can occur with its use. An unusual complication of
      arterioportal fistula is reported here. Based upon this small series of an
      unusual event and the knowledge that the posttransplant liver may be more
      hypervascular than prior to OLTx and that it is uniquely susceptible to hepatic
      infarction and abscess formation, any attempt at fistula closure should be
      considered carefully prior to initiating the therapy (15). Unless a serious
      complication occurs [such as a transient biliary obstruction due to hemobilia as
      occurred in case 2, portal hypertension as also occurred in case 2, or systemic
      sepsis or other symptoms develop related directly to the fistula], simple
      observation may be the best choice of action. Should therapy be required, hepatic
      arterial embolization should be reserved for adults with intrahepatic fistulas.
      Primary surgical closure of intrahepatic fistula should be reserved for cases of
      extrahepatic fistula.

PMID- 7729262
TI  - Chemiluminescent measurement of increased free radical formation after
      ischemia/reperfusion. Mechanisms of free radical formation in the liver.
AB  - It has been proposed that xanthine oxidase-derived superoxide mediates
      reperfusion injury in the liver; however, there is a little direct evidence to
      support this hypothesis. In this paper we describe a model system to directly and
      noninvasively measure oxyradical formation and hepatic injury in isolated
      perfused rat liver. Using this sensitive chemiluminescent technique, we clearly
      demonstrate the theorized burst in oxygen radical production upon reperfusion of
      previously ischemic liver, without perturbing the system with chemical
      luminescence enhancers. This increase in chemiluminescence (CL) upon reperfusion
      was diminished by the free radical scavengers trolox and ascorbate, as well as N
      2-mercaptoproprionyl-glycine (MPG), thereby confirming the oxyradical nature of
      this signal. Additionally, superoxide dismutase and the xanthine oxidase
      inhibitor allopurinol, but not catalase, attenuated the reperfusion effect,
      providing the most direct evidence so far that XOD derived superoxide anion is
      formed during liver reperfusion. Hepatic injury (AST release) did not appear to
      relate to increased CL, supporting the notion that the oxyradical flux may serve
      as a signal for other events leading to tissue injury. Further studies using this
      sensitive chemiluminescent technique should aid in delineating the detailed
      mechanism(s) of reperfusion injury.

PMID- 7729263
TI  - A simple method for ascites concentration and reinfusion.
AB  - A rapid and simple method for ascites concentration and reinfusion was utilized
      to treat 103 episodes of tense ascites in 57 patients (38 men and 19 women, mean
      age 63 +/- 11 years). After a bedside total paracentesis, 6.06 +/- 2.87 liters of
      ascites were separately ultrafiltrated using a mechanical device during a mean
      interval of 134 +/- 88 min, and 430 +/- 368 ml of concentrate containing 39 +/-
      42 g of albumin were restituted at bedside either intravenously (44 cases) or
      intraperitoneally (59 cases). Ultrafiltration was successfully and easily
      completed in all cases. Ascites concentration and reinfusion either intravenously
      or intraperitoneally did not adversely modify hemodynamic or renal parameters
      except for a transient decrease in mean arterial pressure (P < 0.05). Transitory
      hyponatremia and renal failure occurred in two patients. A transient decrease in
      platelet count and serum fibrinogen levels (P < 0.05) and pyrexia (12%) were
      observed only in patients reinfused intravenously. In conclusion, this new method
      for ascites concentration and reinfusion was effective, safe, and, with respect
      to traditional methods, simpler, faster and more comfortable. Therefore it is
      proposed for the routine management of tense ascites.

PMID- 7729264
TI  - Increased renal susceptibility to gentamicin in the rat with obstructive
      jaundice. Role of lipid peroxidation.
AB  - To study whether renal susceptibility to nephrotoxic stimuli is increased in
      obstructive jaundice, the effect of gentamicin on the renal function in bile duct
      ligated rats was investigated. Gentamicin (50 mg/kg/day, subcutaneously) or
      saline was given to bile duct-ligated rats or sham-operated rats for six days.
      Mortality in the bile duct-ligated group that received gentamicin was 64% whereas
      that in the other groups was 0%. In the bile duct-ligated group, although serum
      creatinine and blood urea nitrogen were minimally affected, focal granulo
      vacuolar degeneration in the proximal tubule was observed, which was accompanied
      by an increase in renal malondialdehyde. Gentamicin significantly increased serum
      creatinine and blood urea nitrogen levels and caused marked degeneration in the
      proximal tubule in the bile duct-ligated group, which was accompanied by a
      further increase in renal malondialdehyde, while these changes were not observed
      in the sham group. The kidney in obstructive jaundice appears to be susceptible
      to gentamicin. Enhanced production of oxygen radicals may be responsible for this
      effect.

PMID- 7729265
TI  - Choledocholithiasis in patients with normal serum liver enzymes.
AB  - Retrospective chart review of 330 patients undergoing ERCP over a two-year period
      yielded five patients with choledocholithiasis whose serum liver enzyme and total
      bilirubin levels were repeatedly normal. All were female, three were elderly, and
      the gallbladder was in situ in three of the five, one of whom had a large
      gallbladder remnant. In four patients, the common bile duct was dilated (> 10
      mm), whereas none had intrahepatic duct dilatation. Four patients had a prominent
      ampulla, and stone size varied widely. Each patient was managed with endoscopic
      sphincterotomy and stone extraction followed by cholecystectomy for the four
      patients with the gallbladder or its remnant in situ. This small series proves
      that common duct stones may exist in patients with repeatedly normal serum liver
      enzyme and total bilirubin levels. We hypothesize that marked dilatation of the
      common bile duct or gallbladder may serve as a pressure sump and blunt liver
      enzyme elevation. Normal liver enzymes should not dissuade one from performing
      cholangiography in patients with suspected choledocholithiasis.

PMID- 7729266
TI  - Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome.
      Corticoresistance and effective treatment by cyclosporine A.
AB  - We report a case of primary biliary cirrhosis-autoimmune hepatitis overlap
      syndrome treated with cyclosporine A. Features of primary biliary cirrhosis were
      pruritus, high titer of antimitochondrial antibodies, inflammatory infiltrates
      surrounding interlobular bile ducts, and periportal granuloma. Features
      suggestive of autoimmune hepatitis were high titer of antinuclear antibodies,
      very high total immunoglobulins, and piecemeal necrosis. Because corticosteroids
      and ursodeoxycholic acid were inefficient, cyclosporine A was started at a dose
      of 3 mg/kg/day. A dramatic improvement in clinical condition, liver tests, and
      histology was noted. Discontinuation of cyclosporine A was followed by a clinical
      and histological relapse. Cyclosporine A reintroduction was again associated with
      a significant improvement. This case report suggests that in corticoresistant
      cases cyclosporine A could be an effective therapy for primary biliary cirrhosis
      autoimmune hepatitis overlap syndrome.

PMID- 7729267
TI  - Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of
      gastric acid secretion in humans.
AB  - There is evidence that the distal intestine participates in the regulation of
      gastric motor and secretory function. It was the aim of this study to examine in
      greater detail the effects of ileal nutrient exposure on human gastric acid
      secretion and to investigate potential intermediary mechanisms. Twelve normal
      subjects were intubated with an oroileal multilumen tube assembly for gastric,
      duodenal, and ileal perfusion of marker and test solutions, aspiration, and
      intestinal manometry. We studied ileal effects on gastric acid output in the
      unstimulated, interdigestive state (during early phase II, N = 6), and during
      endogenous stimulation by intraduodenal essential amino acid perfusion, N = 6)
      and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike
      peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion.
      Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60
      kcal) decreased interdigestive gastric acid output by 64% (P < 0.01), and
      endogenously stimulated output by 68%, respectively (P < 0.005). Under all
      experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80-100%
      (all P < 0.005). Ileal lipid perfusion had similar inhibitory effects on gastric
      acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate.
      By contrast, ileal perfusion with peptone had no or only weak effects on either
      acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric
      secretion in response to ileal perfusions were not correlated. In humans, both
      interdigestive and endogenously stimulated gastric acid output are inhibited in
      response to intraileal carbohydrate or lipids, but not protein.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7729268
TI  - Gastric juice ammonia vs CLO test for diagnosis of Helicobacter pylori infection.
AB  - The aim of the present study was to compare the gastric juice ammonia test to the
      CLO test for the diagnosis of H. pylori infection in culture-proven cases by
      receiver operating characteristic (ROC) curve analysis. We studied 75 subjects
      (44 with chronic gastritis, 10 with gastric ulcer, 6 with duodenal ulcer, 8 with
      gastric cancer, and 7 normal) by endoscopy with biopsy for tissue diagnosis,
      culture of H. pylori. CLO test, and by gastric juice ammonia determinations. The
      culture-positive group had significantly higher intragastric ammonia levels (13.7
      +/- 5.8 mg/dl) than the negative group (4.9 +/- 2.4 mg/dl, P < 0.01). In ROC
      curve analysis, the gastric juice ammonia test showed higher true positive and
      lower false positive ratios than the CLO test (P < 0.05). In conclusion, the
      measurement of intragastric juice ammonia levels was considered to be simpler,
      quicker, and overall a more valuable method for diagnosing H. pylori infection.

PMID- 7729269
TI  - An endoscopic study on relationship between Helicobacter pylori infection and
      endoscopic gastric ulcer scars.
AB  - A two-year endoscopic follow-up study of 45 gastric ulcer patients was conducted
      in order to ascertain the relationship between Helicobacter pylori infection, the
      transformation of ulcer scar patterns, and ulcer relapse during maintenance
      therapy. Endoscopic findings of gastric ulcer scar patterns, which established
      the quality of ulcer scars, were classified as follows: Sa, with a central
      depression, Sb, with a coarse regenerating mucosal pattern up to the center, and
      Sc, with a fine pattern. The proportion of ulcer relapses was 62% among 29 H.
      pylori-positive patients and 0% among 16 H. pylori-negative patients. In regard
      to the relationship between H. pylori infection and scar patterns, 94% of the H.
      pylori-negative patients displayed Sc scar patterns, while all the H. pylori
      positive patients showed various scar patterns, ie, Sa in 38%, Sb in 28%, and Sc
      in 10%. Ulcer relapses in the H. pylori-positive cases were limited to the Sa and
      Sb groups (100% and 88%, respectively). In conclusion, our results indicate that
      H. pylori infection plays an important role in the transformation of the ulcer
      scar patterns which relate to ulcer relapse.

PMID- 7729270
TI  - Chronic cough and hoarseness in patients with severe gastroesophageal reflux
      disease. Diagnosis and response to therapy.
AB  - Gastroesophageal reflux may be responsible for atypical symptoms such as chronic
      cough and hoarseness. Our aim was to evaluate and treat patients with severe
      gastroesophageal reflux and chronic cough or hoarseness with intensive antireflux
      therapy. Twenty-seven patients with typical heartburn symptoms in addition to
      significant cough or hoarseness were treated with aggressive antireflux therapy.
      We recorded the response of each symptom to the antireflux therapy. Two patients
      were lost to follow-up. Twenty of the 25 (80%) patients showed some improvement
      in cough or hoarseness, nine (36%) had no atypical symptoms at follow-up. The
      response of heartburn to therapy was strongly predictive of successful therapy
      for the atypical symptoms. Cough and hoarseness improved in only two of the five
      patients with residual heartburn symptoms compared to 18 of 20 patients with no
      heartburn (P < 0.04). Only patients with no heartburn symptoms at follow-up had
      complete resolution of atypical symptoms. There were no important differences on
      ambulatory pH monitoring between partial and complete responders. Improvement in
      atypical reflux symptoms, such as chronic cough and hoarseness, is common with
      aggressive antireflux therapy. There are no findings on ambulatory esophageal pH
      monitoring that uniquely identify patients who are likely to respond to
      antireflux therapy.

PMID- 7729271
TI  - Clinical characteristics and natural history of symptomatic but not excess
      gastroesophageal reflux.
AB  - Esophageal pH monitoring in patients with gastroesophageal reflux symptoms
      identifies some who have normal esophageal acid exposure but nevertheless a
      convincing correlation between symptoms and those reflux events that do occur.
      These patients may exhibit enhanced sensory perception of physiological reflux.
      Little is known about the natural history of reflux symptoms in this group, which
      in our experience comprises up to 6% of those referred for diagnostic pH
      monitoring. We have therefore followed up by postal questionnaire 70 patients
      whose initial pH study had demonstrated normal acid exposure but a symptom index
      > or = 50% and 58 patients found to have excess reflux, for a median of 4.4 and
      6.5 years, respectively. The presenting character and frequency of symptoms and
      endoscopic and manometric findings were similar in the two groups. At review
      overall symptom frequency had improved (P < 0.01) for both groups similarly.
      However, 87% of those with normal acid exposure and 79% of those with excess
      reflux remained symptomatic, 53% and 47%, respectively, recording their symptoms
      to be the same or worse than at original presentation, despite over 60% in each
      group continuing to take regular medication. Only six patients in each group were
      asymptomatic and receiving no therapy at the time of review. The results
      demonstrate that patients with symptomatic but not excess gastroesophageal reflux
      constitute a significant clinical problem. Both the persistence of their symptoms
      and their requirement for therapy are similar to that observed in "genuine"
      refluxers.

PMID- 7729273
TI  - Tobacco cigarette smoke attenuates duodenal ulcer margin hyperemia in the rat.
      Comparison of IAP clearance and hydrogen gas clearance techniques for
      measurements of gastrointestinal blood flow.
AB  - The hyperemia at the duodenal ulcer margin is important for ulcer healing. We
      studied the effect of tobacco cigarette smoke on the hyperemia at the margin of
      mepirizole-induced duodenal ulcer. Duodenal mucosal blood flow values measured by
      iodo[14C]antipyrine (IAP) autoradiography and hydrogen gas clearance (HGC) were
      compared. Twenty-four hours after rats were injected with an ulcerogenic dose of
      mepirizole, they were exposed to tobacco cigarette smoke and duodenal mucosal
      blood flow was measured by IAP autoradiography. There is a significant
      correlation between the blood flow measurements by HGC and IAP autoradiography.
      The hyperemia at the ulcer margin previously demonstrated in our laboratory is
      absent after exposure of the rats to tobacco cigarette smoke. We speculate that
      the inhibition of ulcer margin hyperemia could explain the aggravation of
      duodenal ulcer by tobacco cigarette smoke.

PMID- 7729272
TI  - Discriminant analysis of factors distinguishing patients with functional
      dyspepsia from patients with duodenal ulcer. Significance of somatization.
AB  - Patients with duodenal ulcer or functional dyspepsia do not differ on dyspeptic
      symptoms. The aim of the present study was to test the hypothesis that functional
      dyspepsia and duodenal ulcer are two different diagnostic entities by examining
      the discriminating power of several anamnestic, biological, and psychosocial
      variables. Ninety-four patients with duodenal ulcer and 86 patients with
      functional dyspepsia were included. Anamnestic data, global assessment,
      Helicobacter pylori status, blood group, Lewisa+ phenotype, and several measures
      of psychological distress and somatic complaints were registered. Compared to
      patients with functional dyspepsia, the duodenal ulcer patients were more often
      infected by Helicobacter pylori and had their stomach discomfort more often
      relieved by eating. Compared to patients with duodenal ulcer, patients with
      functional dyspepsia had higher scores of depression, trait anxiety, general
      psychopathology and different somatic complaints (called somatization). They were
      also less satisfied with the health care system, their disorder had a greater
      negative impact on their quality of life, and their global assessment of own
      health was poorer. Discriminant analysis including age, smoking, Helicobacter
      pylori status, global assessment, and somatic complaint classified 86.1% of the
      patients correctly (77.9% of the patients with functional dyspepsia and 93.6% of
      the patients with duodenal ulcer). It is concluded that duodenal ulcer and
      functional dyspepsia are two separate diagnostic entities. Patients with duodenal
      ulcer are older, smoke more often, and almost all are infected with Helicobacter
      pylori, while patients with functional dyspepsia are characterized by
      somatization and a negative assessment of their own health.

PMID- 7729274
TI  - Aggravation of gastric mucosal lesions in rat stomach by tobacco cigarette smoke.
AB  - In the model of gastric mucosal injury induced by 2 mol/liter hypertonic saline
      in rats, we tested the hypothesis that tobacco cigarette smoke aggravates gastric
      mucosal lesions by inhibition of injury-induced gastric mucosal hyperemia.
      Experimental rats were treated with tobacco cigarette smoke or nicotine-free
      smoke from nontobacco cigarettes, and controls breathed room air. Gastric mucosal
      blood flow was measured by hydrogen gas clearance before and during the
      intragastric administration of hypertonic saline. Tobacco cigarette smoke 3 and
      18 ml/min, but not nicotine-free smoke, significantly attenuated the hyperemia
      and aggravated the hypertonic saline-induced lesion in a dose-dependent manner.
      We then tested the hypothesis that 18 ml/min of tobacco cigarette smoke, and the
      dose of intravenous nicotine previously shown to block injury-induced hyperemia
      and aggravate 2 mol/liter saline-induced gastric damage, will also adversely
      affect gastric lesions induced by acidified aspirin or acidified ethanol. The
      results confirm that tobacco cigarette smoke and intravenous nicotine indeed
      aggravate gastric mucosal damage in these two models. Taken together, the data
      suggest that the inhibition of injury-induced hyperemia by nicotine and tobacco
      cigarette smoke is an important predictor of their ability to increase the
      susceptibility of the gastric mucosa to noxious damage. Although limited in their
      experimental nature, these data provide one plausible explanation for the adverse
      effect of tobacco cigarette smoke on peptic ulcer disease.

PMID- 7729275
TI  - Misoprostol coadministered with diclofenac for prevention of gastroduodenal
      ulcers. A one-year study.
AB  - The objective of this study was to determine the long-term efficacy of
      misoprostol in preventing diclofenac-induced gastroduodenal ulcers in rheumatoid
      arthritis and osteoarthritis patients. Three hundred eighty-four patients who had
      an endoscopically confirmed gastric or duodenal lesion that had healed with
      misoprostol therapy were randomized to receive misoprostol or placebo
      coadministered with diclofenac for up to 52 weeks. Endoscopic examinations were
      repeated at weeks 12, 24, and 52. The development of a gastric and/or duodenal
      ulcer was considered a prophylaxis failure. Results in the evaluable cohort of
      patients demonstrated that gastroduodenal ulcer incidences were lower with
      misoprostol than placebo for all study periods (0-12 weeks, 7% vs 23%; 0-24
      weeks, 11% vs 26%; and 0-52 weeks, 15% vs 31%). Misoprostol did not interfere
      with the antiarthritic effects of diclofenac. In conclusion, misoprostol
      coadministered with diclofenac for 12 months to patients with rheumatoid
      arthritis or osteoarthritis significantly reduced the incidence of diclofenac
      induced gastroduodenal ulcers (P < or = 0.018).

PMID- 7729276
TI  - Roles of hepatocyte growth factor and its receptor in gastric mucosa. A cell
      biological and molecular biological study.
AB  - Hepatocyte growth factor (HGF) stimulates the growth of hepatocytes and other
      epithelial cells. A gene for the HGF receptor, c-met, is detected in the
      intestinal tract and the liver, as well as in gastric carcinoma cells. However,
      the role of HGF in the regeneration of the normal gastric mucosa is not known.
      The purpose of the present study was to elucidate the effects of HGF on the
      morphogenesis of cultured gastric mucosal cells and to evaluate the role of HGF
      and c-met in the healing process in rat gastric mucosa. The cultured gastric
      mucosal cells developed a branching morphology in a collagen matrix supplemented
      with HGF or fetal calf serum. They did not form this morphology on a plastic dish
      or in the collagen without HGF or the serum. In an in vivo study, total RNA was
      extracted from rat gastric mucosa 6, 24, 48, and 96 hr after the exposure to a
      solution of 0.6 M HCl. HGF messenger RNA was not detected, but c-met was
      expressed in the mucosa. The increased expression of c-met was followed by
      healing of the mucosal injury. These results indicate that HGF plays important
      roles in the morphogenesis of gastric mucosal cells and that the HGF receptor
      gene participates in the healing process of gastric mucosa.

PMID- 7729277
TI  - Ketotifen and nitroxides decrease capsaicin-augmented ethanol-induced gastric
      damage in rats.
AB  - Systemic administration of capsaicin aggravates ethanol-induced injury of rat
      gastric mucosa. We evaluated the effect of subcutaneous administration of
      capsaicin on the gastric mucosa and on inflammatory mediators in saline- and
      ethanol-treated rats. Functional ablation of primary afferent C-fibers by
      capsaicin (total 100 mg/kg subcutaneous) tripled ethanol-induced damage.
      Pretreatment with ketotifen, a mast cell stabilizer (1 mg/kg) protected rat
      gastric mucosa from the amplified injury induced by capsaicin and ethanol.
      Tempol, a selective nontoxic cell-permeable nitroxide, completely prevented the
      amplified gastric ulceration induced by capsaicin and ethanol. This was
      accompanied by a significant decrease in leukotriene B4 and C4 generation. It is
      therefore suggested that mast cells and free radicals contribute to the amplified
      injury observed in rats pretreated with capsaicin and ethanol and that the
      pharmacological modulation of mast cell release and scavenging of free radicals
      may be of therapeutic efficacy in the prevention of gastric injury.

PMID- 7729278
TI  - Use of thalidomide in treatment and maintenance of idiopathic esophageal ulcers
      in HIV+ individuals.

PMID- 7729279
TI  - Abnormal sphincter of Oddi response to cholecystokinin in postcholecystectomy
      syndrome patients with irritable bowel syndrome. The irritable sphincter.
AB  - Standard biliary manometry, including cholecystokinin (CCK) provocation, was
      performed on 42 consecutive patients (36 F, 6 M, median age 45 years) with
      postcholecystectomy syndrome (PCS) who had no evidence of organic disease but who
      had objective clinical features suggesting sphincter of Oddi dysfunction (SOD)
      (classes I and II). Patients were subdivided into those with (N = 14) and without
      (N = 28) irritable bowel syndrome (IBS) using a validated symptom questionnaire
      based on the modified Rome criteria. Resting sphincter of Oddi (SO) motor
      parameters (basal pressure, contractile amplitude and frequency, and proportion
      of retrograde contractions), the presence of abnormal manometry, and the presence
      of an abnormal response to CCK were compared in the two groups. No significant
      differences in resting parameters of SO motor activity between patients with and
      without IBS were observed, and abnormal biliary manometry as a whole was not more
      prevalent in either group (8/13 and 18/27, respectively). An abnormal response to
      CCK (failure of complete inhibition of phasic contractions), however, was
      demonstrated in five of 12 patients with IBS compared with only one of 23
      patients without IBS (P = 0.01). In patients with postcholecystectomy SOD, an
      abnormal response of the SO to CCK thus appears to be an important feature of the
      subset of patients with concomitant IBS.

PMID- 7729280
TI  - Gallbladder mucosal protein secretion during development of experimental
      cholecystitis.
AB  - The development of experimental cholecystitis produced by lysophosphatidylcholine
      is associated with reversal of the normal absorptive characteristics of
      gallbladder mucosa, resulting in the intraluminal accumulation of water,
      glycoprotein, and protein. The purpose of the present study was to attempt to
      ascertain if the protein leaks into the lumen because of the cytolytic properties
      of lysophosphatidylcholine or if it is due to an active secretory process and to
      characterize the protein produced. Experiments were performed on anesthetized
      cats undergoing gallbladder perfusion with and without lysophosphatidylcholine.
      The amount of protein in the perfusate was measured and albumin clearance from
      blood to gallbladder lumen was calculated with and without the administration of
      vesicular transport inhibitors. In separate experiments, control and
      lysophosphatidylcholine (LPC) produced gallbladder perfusates were collected and
      the protein subjected to SDS-PAGE to ascertain the nature of the protein
      secreted. Inhibitors of both microtubular and microfilament activity decreased
      the protein accumulation and clearance produced by lysophosphatidylcholine.
      Gallbladder white blood cell accumulation and inflammation as evaluated by beta
      glucuronidase and prostaglandin E levels were not significantly altered by
      cytochalasin or colchicine administration. Lysophosphatidylcholine also produced
      significant increases in perfusate LDH levels. The protein produced was primarily
      a 66-kDa protein. Transfer of the protein to a nitrocellulose membrane and
      immunoblotting with anti-albumin antibody demonstrated that the protein was
      albumin. The results suggest that during the development of cholecystitis,
      lysophosphatidylcholine produces albumin accumulation in the gallbladder
      primarily by inducing an active secretory process resulting in gallbladder
      distension.

PMID- 7729281
TI  - Quality-of-life results of double-blind, placebo-controlled trial of mesalamine
      in patients with Crohn's disease.
AB  - Seven quality-of-life parameters were assessed in a trial of mesalamine in
      Crohn's disease. The results with regard to efficacy and safety have been
      previously published. A total of 310 patients were enrolled in this double-blind,
      parallel trial and randomized to receive placebo, or 1, 2, or 4 g/day of
      mesalamine in controlled-release capsules for 16 weeks. Results revealed that
      mesalamine at the dose of 4 g/day resulted in significant (P < 0.03) improvements
      from baseline in all quality-of-life parameters. A significant (P < 0.02) linear
      trend between increasing doses of mesalamine and increasing response was also
      noted. The 1- and 2-g/day doses of mesalamine also resulted in an improvement in
      quality of life, however, with the exception of 2 g/day of mesalamine on the
      hobby and recreational activities parameter, these changes were not significantly
      different from placebo.

PMID- 7729282
TI  - Topical nicotine protects rat gastric mucosa against ASA-induced damage. A role
      for mucosal fluid secretion in cytoprotection.
AB  - Acute intragastric nicotine administration has previously been shown to protect
      against ethanol-induced gastric mucosal damage. The aim of this study was to
      examine the effects of acute nicotine exposure on ASA-induced gastric mucosal
      damage and to determine if nicotine's protective effect is secondary to an
      increase in mucosal blood flow or in mucosal fluid secretion, as reflected by
      changes in the juxtamucosal pH gradient and volume of intragastric fluid. Mucosal
      blood flow, using a laser Doppler flowmeter, juxtamucosal pH gradient (depth,
      magnitude, and surface pH), using antimony microelectrodes, and changes in volume
      of luminal bathing solutions were measured in rat ex vivo gastric chamber
      preparations prior to and after a 10-min exposure to topical nicotine (1 mg in 8
      ml of 0.2 M mannitol in 50 mM HCl), or to mannitol-HCl solution (vehicle). This
      was followed by application of acidified ASA (80 mM in 160 mM HCl) to the
      chambered mucosae for 10 min. Lesion area, expressed as the percentage of total
      glandular mucosa which was damaged, was significantly (P < 0.05) reduced by
      nicotine pretreatment. Blood flow decreased with nicotine exposure by 18.4%,
      compared to 13.6% in the control group (NS). Both gradient depth and gastric
      fluid volume increased significantly in the nicotine group (P < 0.05) compared to
      controls. Yohimbine pretreatment prevented both the increase in juxtamucosal pH
      gradient depth and the protective effect of nicotine. These results suggest that
      acute intragastric nicotine exposure protects against ASA-induced gastric damage
      in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729283
TI  - Effect of olsalazine on sodium-dependent bile acid transport in rat ileum.
AB  - Olsalazine (OLZ), a relatively new form of 5-aminosalicylic acid (5-ASA), is
      being used for the treatment of colitis. A major side effect of olsalazine is
      diarrhea, reported in 12-25% of patients. One suggested mechanism for this side
      effect is enhanced ileal water and electrolyte secretion. We propose that OLZ may
      also inhibit ileal bile acid (BA) transport, resulting in choleretic diarrhea.
      This would result in excess BAs reaching the colon, with consequent BA-induced
      secretory diarrhea. Therefore, we studied the effect of OLZ on rat ileal
      absorption of taurocholate. BA uptake was determined in rat ileal segments,
      everted sacs, brush border membrane vesicles (BBMV), and Xenopus laevis oocytes.
      Segments and everted sacs were treated with 5 mM OLZ for 30 min prior to and
      throughout 10-min taurocholate (Tc) uptake. Terminal ileal BBMV were used to
      study the effect of OLZ on sodium-dependent bile acid uptake independent of
      cellular metabolism. Direct effects on the bile acid carrier were examined using
      Xenopus laevis oocytes expressing the cloned apical rat ileal BA transporter. In
      ileal segments 5 mM OLZ inhibited 10-min Tc uptake by 69.4 +/- 8.8% (P < 0.01) (N
      = 10 animals). Increasing concentrations of OLZ resulted in a dose-dependent
      inhibition of Tc uptake. Ten-minute Tc uptake with 0.5, 1.0, 2.0, 2.5, and 5 mM
      OLZ was inhibited by 13.5, 39.6, 49.7, and 70.5%, respectively. In BBMV, OLZ
      inhibited 45-sec Tc uptake in a dose-dependent manner but did not effect Na
      dependent L-alanine uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729284
TI  - Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and
      epithelial cell-dependent.
AB  - Local interleukin-6 (IL-6) activity was studied using colonic mucosal tissues in
      inflammatory bowel disease (IBD) and inflammatory control patients. Active IBD
      specimens exhibited significantly higher IL-6 activity than control specimens in
      both cultures of isolated lamina propria mononuclear cells (LPMC) and mucosal
      tissues with an increased number of IL-6-producing cells. However, the activity
      in inactive IBD or inflammatory controls did not differ from controls. Northern
      blot analysis demonstrated IL-6 messenger RNA in LPMC and colonic epithelial
      cells isolated from active IBD specimens but not in control cells. Furthermore,
      immunofluorescent microscopic study of active IBD specimens showed more
      conspicuous staining of IL-6 in infiltrating LPMC (mostly CD68+ cells) and
      colonic epithelial cells. These results suggest that elevation of local IL-6
      activity may be a characteristic feature of active IBD and both macrophages and
      colonic epithelial cells are the major cell types responsible for this
      phenomenon.

PMID- 7729285
TI  - Changes in intestinal tunica muscularis following dietary fiber feeding in rats.
      A morphometric study using image analysis.
AB  - The morphological changes in the intestinal tunica muscularis induced by
      prolonged dietary fiber intake were determined in rat small intestine and colon
      with the aid of computerized image analysis. Thirty male Sprague-Dawley rats were
      fed either a fiber free, 15% cellulose or 15% pectin diet for 8 weeks. Intestine
      length was measured and stained cross sections of the jejunum, ileum, and colon
      were quantitated using image analysis. In the distal colon, muscle cell size was
      also determined. Despite lower weight gain in the pectin fed rats, both the small
      intestine and colon length were significantly increased. Cellulose feeding had a
      lesser effect on intestine length. Pectin fed rats had significantly increased
      relative tunica muscularis area (37.2 +/- 2.2 mm2) in ileum cross sections when
      compared to control (24.3 +/- 1.8 mm2) and cellulose fed rats (26.1 +/- 1.1 mm2).
      In the mid-colon, the tunica muscularis area was found to be pectin > cellulose >
      control (33.5 +/- 2.2; 29.7 +/- 1.7; 25.8 +/- 1.5 respectively) with significant
      differences reached between pectin and control rats. In jejunal samples, no
      differences were observed among the groups. Circular smooth muscle cell size in
      the distal colon was significantly increased following cellulose feeding but was
      less pronounced in the case of pectin. We conclude that fiber supplementation
      leads to morphological changes in the rat intestine including changes in length
      and tunica muscularis volume.

PMID- 7729286
TI  - Uptake and translocation of microparticles in small intestine. Morphology and
      quantification of particle distribution.
AB  - The intestinal transit of large (micro-) particles to other sites of the body
      remains a controversial issue of relevance in various fields of study. In this
      report fluorescent polystyrene latex microparticles in the size range of 2
      microns were used as models for nonspecifically absorbed nonbiodegradable
      particulates. They were administered to young adult rats as a single oral dose of
      1.65 x 10(9) particles; Peyer's patches and surrounding normal absorptive small
      intestinal tissue were collected at various time points. Quantification of
      solubilized tissue samples and fluorescence (epi- and confocal) qualitative and
      quantitative microscopy showed uptake of latex microparticles in all parts of the
      intestine sampled, but with the proximal segment the preferential site of
      absorption. The maximum uptake of particles occurred 0.5 hr after dosing in all
      three segments of the small intestine; there were progressively smaller numbers
      with distance from the pylorus and with time. Translocation of small numbers of
      particles to the mesenteric lymph nodes was also detected at 0.5 hr. Transmucosal
      passage of particles occurred primarily in the villous tissues adjacent to the
      Peyer's patch regions. These studies give confirmatory evidence for the uptake
      and translocation of microparticulates across the mucosal barrier and provide new
      information regarding site- and time-related effects on particle uptake and the
      involvement of the villous epithelium in particle translocation.

PMID- 7729287
TI  - Passive elastic wall properties in isolated guinea pig small intestine.
AB  - The aim was to study and compare the passive biomechanical wall properties in the
      isolated duodenum and distal ileum of the guinea pig in vitro. The organ bath
      contained a Krebs-Ringer solution with 10(-2) M MgCl2 to abolish smooth muscle
      contractile activity. Stepwise inflation of an intraluminal balloon, in which the
      cross-sectional area (CSA) was measured, provided the distension stimulus. The
      circumferential wall tension-strain distributions and wall stiffness-strain
      relations were computed from steady-state values of these measurements in order
      to evaluate the passive elastic properties. The CSA always reached equilibrium
      within the 2-min distension period. The CSAs obtained in the distal ileum were
      higher than those in the duodenum (P < 0.001). The basal CSA was 17.31 +/- 1.14
      mm2 and 12.96 +/- 0.42 mm2 for the distal ileum and the duodenum, respectively (P
      < 0.01). At a maximum pressure of 6 kPa, the CSA of the ileum was 56.63 +/- 1.81
      mm2 and 36.86 +/- 1.76 mm2 for the duodenum (P < 0.01). The circumferential wall
      tension-strain distributions showed an exponential behavior that accorded well
      with the equation Y = exp(a+bX) with determination coefficients of 0.96 +/- 0.01
      and 0.99 +/- 0.00 in the duodenal segments in the distal ileal segments,
      respectively. The values of a (intercept with the y-axis) were 0.54 +/- 0.11 and 
      0.35 +/- 0.19 for the duodenal and ileal segments, respectively (P < 0.001). The
      slope of the curves (b values) were 4.34 +/- 0.35 in the duodenal and 5.23 +/-
      0.37 in the ileal segments (0.1 > P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729288
TI  - A study of irritable bowel syndrome diagnosed by Manning criteria in an African
      population.
AB  - Symptoms of irritable bowel syndrome (IBS) using the Manning Criteria were sought
      by a questionnaire administered to 400 (male-female ratio 3:1) apparently healthy
      medical students. With a response rate of 84%, 230 (65.5%) reported more than six
      episodes of abdominal pain in the preceding year (1992-1993). Contrary to
      expectation, 100 (43.5%) reported symptoms consistent with the diagnosis of IBS.
      The one-year period prevalence of the syndrome was 30% overall, with prevalence
      figures of 24% for males and 48% for females (P < 0.01). There was no difference
      in the type of diet (mainly high-fiber diets) consumed by subjects with and
      without IBS. About two thirds of the subjects with IBS had sought medical advice
      during the study period; the consultation behavior was influenced by factors such
      as the presence of other symptoms. This is the first detailed evidence in a
      random sample of an African population showing symptoms consistent with a
      diagnosis of IBS to be very common. It casts doubt on the assumption generated by
      other workers that IBS is rare among native Africans.

PMID- 7729289
TI  - Functional bowel disorders. A multicenter comparison of health status and
      development of illness severity index.
AB  - In a multicenter study of patients with painful functional bowel disorders (FBD),
      we compared the demographic, health status, and diagnostic features of patients
      with FBD and developed a functional bowel disorder severity index (FBDSI) for
      research and clinical care. Two hundred seventy patients with FBD in the United
      States, England, and Canada were surveyed on symptoms and health status, and
      their physicians made a diagnosis and rated illness severity as mild, moderate,
      or severe. Comparisons of 22 demographic and clinical variables were made by
      study site in addition to physicians' severity ratings. To develop the FBDSI,
      multiple regression analysis used the demographic and clinical variables to
      predict the physician's rating of severity. We found that most health status
      measures of patients with FBD across study sites are comparable and the derived
      and validated FBDSI scoring system uses three easy to obtain variables: FBDSI =
      [current pain by visual analog scale (0-100)] + [diagnosis of chronic functional
      abdominal pain (0 if absent and 106 if present)] + [number of physicians visits
      over previous six months x 11]. The FBDSI can be used to select patients for
      research protocols and/or follow their clinical outcome or response to treatments
      over time.

PMID- 7729290
TI  - DNA ploidy and proliferating cell nuclear antigen in colonic adenomas and
      adenocarcinomas.
AB  - To investigate the colonic adenoma-adenocarcinoma progression sequence, DNA
      ploidy analysis was performed on hyperplastic polyps to adenocarcinomas. DNA
      ploidy data were then compared with immunocytochemical staining for proliferating
      cell nuclear antigen (PCNA). In hyperplastic polyps to villous adenomas, all
      cases were diploid except one aneuploid villous adenoma. In three adenomas,
      diploid in situ adenocarcinomas were present. As diploid percentages decreased
      from hyperplastic polyps to villous adenomas, aneuploid percentages increased. In
      adenocarcinomas, the Dukes classification corresponded well to DNA ploidy status:
      all four stage A carcinomas were diploid, whereas three cases each of stage C1
      and C2 carcinomas were aneuploid or multiploid. A surprising finding was that S
      phase percentage in adenocarcinomas was not parallel with PCNA-positive tumor
      cell numbers. It is concluded that multistep adenoma-adenocarcinoma progression
      was partially reflected in DNA ploidy pattern from hyperplastic polyps to villous
      adenomas. In adenocarcinomas, the Dukes classification paralleled well the DNA
      ploidy status from stage A diploid to stage D aneuploid, but was not accompanied
      by increasing PCNA-positive cell numbers.

PMID- 7729291
TI  - Diabetes and pregnancy. Factors associated with seeking pre-conception care.
AB  - OBJECTIVE: To define sociodemographic characteristics, medical factors,
      knowledge, attitudes, and health-related behaviors that distinguish women with
      established diabetes who seek pre-conception care from those who seek care only
      after conception. RESEARCH DESIGN AND METHODS: A multicenter, case-control study
      of women with established diabetes making their first pre-conception visit (n =
      57) or first prenatal visit without having received pre-conception care (n = 97).
      RESULTS: Pre-conception subjects were significantly more likely to be married (93
      vs. 51%), living with their partners (93 vs. 60%), and employed (78 vs. 41%); to
      have higher levels of education (73% beyond high school vs. 41%) and income (86%
      > $20,000 vs. 60%); and to have insulin-dependent diabetes mellitus (IDDM) (93
      vs. 81%). Pre-conception subjects with IDDM were more likely to have discussed
      pre-conception care with their health care providers (98 vs. 51%) and to have
      been encouraged to get it (77 vs. 43%). In the prenatal group, only 24% of
      pregnancies were planned. Pre-conception patients were more knowledgeable about
      diabetes, perceived greater benefits of pre-conception care, and received more
      instrumental support. CONCLUSIONS: Only about one-third of women with established
      diabetes receive pre-conception care. Interventions must address prevention of
      unintended pregnancy. Providers must regard every visit with a diabetic woman as
      a pre-conception visit. Contraception must be explicitly discussed, and
      pregnancies should be planned. In counseling, the benefits of pre-conception care
      should be stressed and the support of families and friends should be elicited.

PMID- 7729292
TI  - Maternal metabolic control and risk of microcephaly among infants of diabetic
      mothers.
AB  - OBJECTIVE: To measure the incidence of microcephaly among infants of diabetic
      mothers (IDM) and assess its relationship to metabolic control during pregnancy.
      RESEARCH DESIGN AND METHODS: Head circumference data for 556 consecutive live
      born singleton infants of women with insulin-requiring diabetes antedating
      pregnancy delivered between 28 and 40 weeks of gestation and the results of 3,242
      HbA1 determinations collected during their pregnancies were examined. RESULTS:
      There were fewer head circumferences at or below the 3rd percentile and more at
      or above the 97th percentile than expected. Head circumference was not related to
      maternal metabolic control as documented by the HbA1 values. CONCLUSIONS: The
      less-than-expected incidence of microcephaly observed in this patient population
      probably reflects the well-known tendency of IDM toward macrosomia.

PMID- 7729293
TI  - Anti-bovine serum albumin antibodies: genetic heterogeneity and clinical
      relevance in adult-onset IDDM.
AB  - OBJECTIVE: To evaluate the prevalence of anti-bovine serum albumin (BSA)
      antibodies in patients with adult-onset insulin-dependent diabetes mellitus
      (IDDM) and investigate a possible link between their presence and genetic
      susceptibility or resistance determined by human leukocyte antigen (HLA) complex.
      RESEARCH DESIGN AND METHODS: Sera from 60 recent-onset diabetic patients, 5
      prediabetic subjects, and 102 healthy control subjects were tested using a
      radioimmunoprecipitation assay. HLA-DRB and -DQB alleles were determined by means
      of allele-specific oligonucleotide typing. Islet cell antibodies (ICAs) were
      assayed by indirect immunofluorescence. RESULTS: Levels of anti-BSA antibodies
      were significantly higher in IDDM patients (18.1 +/- 3.5%, n = 60) than in
      healthy control subjects (7.5 +/- 1.2%, n = 102) (P < 0.001), but in only 16.6%
      of IDDM patients (10 of 60) were the titers above the 95th percentile of control
      values. Anti-BSA antibody titers were higher in HLA-DR3 and/or -DR4 patients
      (23.4 +/- 4.9%, n = 41) compared with DR3 and/or DR4 control subjects (3.1 +/-
      1.0%, n = 10) (P < 0.001). DR3 IDDM patients showed higher levels of anti-BSA
      antibodies (26.3 +/- 6.3%, n = 30) than non-DR3 patients (9.9 +/- 2.6%, n = 30)
      (P < 0.01) and healthy control subjects. Only two out of five prediabetic
      subjects had significant anti-BSA levels before clinical onset of diabetes.
      CONCLUSIONS: Our data confirm that antibodies to BSA are present in adult-onset
      IDDM patients, particularly in HLA-DR3-positive patients. However, the prevalence
      of anti-BSA antibodies was lower than previously reported in children, and there
      was a considerable overlap with healthy control subjects. Only two out of the
      five prediabetic patients demonstrated anti-BSA antibodies. Taken together, these
      results do not bring strong support to the clinical usefulness of anti-BSA
      antibodies as a relevant marker in diabetes prediction or diagnosis.

PMID- 7729294
TI  - Visceral adiposity, fasting plasma insulin, and blood pressure in Japanese
      Americans.
AB  - OBJECTIVE: To examine the associations among blood pressure, body mass index
      (BMI), intra-abdominal fat, and fasting plasma insulin levels among nondiabetic
      subjects. RESEARCH DESIGN AND METHODS: Second- (Nisei, n = 290) and third-
      (Sansei, n = 230) generation Japanese-American subjects without non-insulin
      dependent diabetes mellitus (NIDDM) were selected from a community-based study of
      NIDDM incidence and complications. A cross-sectional comparison of measures
      obtained at the baseline visit was performed. Intra-abdominal fat (IAF) area was
      assessed using computed tomography. Associations among blood pressure, fasting
      insulin, and adiposity measures were assessed by comparison of mean values and
      multiple linear regression analysis. RESULTS: Hypertensive men and women had
      significantly higher mean IAF areas. Fasting insulin levels were somewhat higher
      in hypertensive subjects, with the only significant difference occurring among
      Sansei men. Both systolic and diastolic blood pressure correlated more strongly
      with IAF than BMI or skinfold thicknesses among Nisei, whereas among Sansei, IAF
      and BMI correlated equally well with either blood pressure. Significant positive
      correlations were found between fasting insulin level and blood pressure among
      Sansei only, even after adjustment for IAF and BMI (diastolic blood pressure
      insulin coefficient = 0.24, P = 0.0043; systolic blood pressure-insulin
      coefficient = 0.36, P = 0.0025). CONCLUSIONS: IAF correlated more strongly with
      blood pressure than BMI or skinfold thicknesses among older, second-generation
      Japanese-Americans and was positively correlated with blood pressure among Sansei
      independent of fasting insulin level. Fasting insulin was significantly
      correlated with blood pressure independent of visceral and overall adiposity
      among third-generation Japanese-Americans.

PMID- 7729295
TI  - Incidence and determinants of elevated urinary albumin excretion in Pima Indians
      with NIDDM.
AB  - OBJECTIVE: To examine the incidence and determinants of elevated urinary albumin
      excretion in Pima Indians with non-insulin-dependent diabetes mellitus (NIDDM).
      RESEARCH DESIGN AND METHODS: The incidence of elevated urinary albumin excretion
      (> or = 30 mg albumin/g creatinine) and its relationship with baseline
      characteristics was determined in 456 Pima Indians > or = 15 years old with NIDDM
      who were followed for up to 11.6 years (median 4.7 years). RESULTS: Of these 456
      subjects, 192 (42%; 58 men, 134 women) developed elevated urinary albumin
      excretion, 172 of whom (90%) were within the microalbuminuric range (30-299
      mg/g). The incidence of elevated urinary albumin excretion was related to
      retinopathy, type, of diabetes treatment, longer duration of diabetes, lower body
      mass index, and higher values of mean arterial pressure, HbA1, and fasting and 2
      h postload plasma glucose concentration at the baseline examination, but not to
      sex. A relationship with cholesterol was found in durations of diabetes of > or =
      10 years. The cumulative incidence of elevated albumin excretion was 17% after 5
      years of NIDDM. CONCLUSIONS: The incidence of elevated urinary albumin excretion
      in Pima Indians with NIDDM is at least as high as that reported previously in
      insulin-dependent diabetes mellitus, and its major determinants are the same as
      those shown previously to predict the development of more advanced renal disease
      in this population.

PMID- 7729296
TI  - Hypomagnesemia in type II diabetes: effect of a 3-month replacement therapy.
AB  - OBJECTIVE: To investigate the effects of long-term high-dose oral magnesium (Mg)
      therapy (30 mmol/day) in patients with type II diabetes. Low plasma magnesium
      levels have been reported in type II diabetes and are associated with insulin
      resistance and diabetic late complications. RESEARCH DESIGN AND METHODS: Forty
      patients with type II diabetes and hypomagnesemia were observed in a randomized
      double-blind placebo-controlled trial for 3 months (body mass index: 28 +/- 4
      kg/m2; HbA1c: 7.4 +/- 0.8%). Plasma and urine magnesium and metabolic control
      parameters were determined, and side effects were considered, especially with
      regard to patients' compliance. RESULTS: A significant increase in plasma
      magnesium levels was observed after 3 months of treatment (Mg: 0.73 +/- 0.8 vs.
      0.81 +/- 0.1 mmol/l), reaching magnesium levels of the control group (0.88 +/-
      0.8 mmol/l; NS); metabolic control, however, was not altered (HbA1c: 7.2 +/- 0.7
      vs. 7.4 +/- 0.9%). Six months after the end of the trial, plasma magnesium
      declined to pretreatment levels (Mg: 0.73 +/- 0.07 mmol/l). The prevalence of
      side effects was high at the beginning and was reduced significantly during
      treatment. CONCLUSIONS: We conclude that oral magnesium replacement therapy
      corrects hypomagnesemia after a minimum treatment period of 3 months. These
      observations might be important for the prevention of diabetic late
      complications.

PMID- 7729297
TI  - Insulin sensitivity and Lp(a) concentrations in normoglycemic men.
AB  - OBJECTIVE: Increased lipoprotein(a) [Lp(a)] concentrations have been recognized
      as a risk factor for coronary heart disease. Little data exists on the
      relationship of Lp(a) concentrations to insulin resistance. RESEARCH DESIGN AND
      METHODS: We examined insulin resistance (as determined by the euglycemic clamp)
      together with indirect calorimetry in relation to Lp(a) concentrations,
      apolipoprotein(a) [apo(a)] molecular weight, and apo(a) phenotype in 87
      normoglycemic men. RESULTS: Lp(a) concentrations were significantly related to
      total (r = 0.225) and nonoxidative (r = 0.256) whole-body glucose disposal. These
      results suggest a positive but weak association between insulin sensitivity
      (restricted to the nonoxidative whole-body glucose disposal) and Lp(a)
      concentrations. However, after adjustment for apo(a) molecular weight [which
      accounts for some of the genetic influences on Lp(a) levels], total and
      nonoxidative body glucose disposal were not significantly related to Lp(a)
      concentrations. CONCLUSIONS: Normoglycemic insulin-resistant subjects do not have
      elevated Lp(a) concentrations.

PMID- 7729298
TI  - Effects of personality on metabolic control in IDDM patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between poor
      metabolic control and maladaptive personality traits (according to the Diagnostic
      and Statistical Manual of Mental Disorders, Third Edition-Revised) in an adult
      onset insulin-dependent diabetes mellitus sample group (n = 77). RESEARCH DESIGN
      AND METHODS: Metabolic control was evaluated through glycosylated hemoglobin
      (HbA1c). Personality traits were assessed with the Personality Diagnostic
      Questionnaire-Revised, a self-administered questionnaire. Residual pancreatic
      secretion (fasting serum C-peptide) was also evaluated. RESULTS: Principal
      components analysis revealed three personality profiles: "withdrawn-suspicious"
      (P1), "dramatic-dependent" (P2), and "aggressive-irresponsible" (P3). Multiple
      linear regression analysis showed that C-peptide levels and P2 personality
      profiles were significant and independent predictors of HbA1c plasma levels: P2
      predicted high HbA1c values and C-peptide predicted low HbA1c levels.
      CONCLUSIONS: These data suggest that a P2 personality profile is a significant
      predictor of poor metabolic control.

PMID- 7729299
TI  - No association of antibodies to glutamic acid decarboxylase and diabetic
      complications in patients with IDDM.
AB  - OBJECTIVE: To evaluate the association of antibodies to glutamic acid
      decarboxylase (GAD-ab) and diabetic complications (neuropathy, retinopathy, and
      nephropathy) in patients with insulin-dependent diabetes mellitus (IDDM).
      RESEARCH DESIGN AND METHODS: We examined the prevalence of GAD-ab
      (immunoprecipitation assay) and islet cell antibodies (ICAs) (indirect
      immunofluorescence) in a representative sample of IDDM patients (n = 146) with
      different disease duration (2-52 years, median 13.2 years). Of all patients
      characterized for the existence of diabetic complications, 56 of 146 had
      peripheral neuropathy, 24 of 142 had autonomic neuropathy, 67 of 141 had
      retinopathy, and 39 of 146 had nephropathy. RESULTS: GAD-ab (> 2 SD) were
      detected more frequently than ICA (> 5 Juvenile Diabetes Foundation units) in
      IDDM patients of different disease duration (GAD-ab+ 37% [54 of 146] vs. ICA+ 22%
      [32 of 146], P = 0.011; diabetes duration less than median: GAD-ab+ 47% vs. ICA+
      23%, P = 0.0046; diabetes duration greater than median: GAD-ab+ 27% vs. ICA+ 22%,
      P > 0.05). For GAD-ab and for ICA, respectively, no difference was observed in
      frequency of positivity or titers between patients with or without diabetic
      complications. CONCLUSIONS: Both GAD-ab and, to a lesser extent, ICA persist for
      a long time in several individuals. This persistence is not related to diabetic
      neuropathy or any other diabetic complication.

PMID- 7729300
TI  - The independent contributions of diabetic neuropathy and vasculopathy in foot
      ulceration. How great are the risks?
AB  - OBJECTIVE: To describe the relative contributions of neurological and vascular
      abnormalities to the overall risk of diabetic foot ulceration. RESEARCH DESIGN
      AND METHODS: A case-control study of diabetic veterans from the Seattle Veterans
      Affairs Medical Center was conducted using data collected from 46 patients with
      diabetic foot ulcers and 322 control subjects. Neuropathy was determined by
      vibratory, monofilament, and tendon reflex testing. Macrovascular disease was
      measured by ankle-arm blood pressure index, and cutaneous perfusion was measured
      by transcutaneous oxygen tension (TcPO2) on the dorsal foot. A multivariate
      logistic regression model was used to adjust for confounding variables and to
      calculate the odds ratios (ORs) for each independent risk factor. RESULTS: Three
      variables were significant independent predictors of foot ulceration: absence of
      Achilles tendon reflexes (adjusted OR 6.48, 95% confidence interval [CI] 2.37
      18.06), insensate to the 5.07 monofilament (adjusted OR 18.42, 95% CI 3.83
      88.47), and TcPO2 < 30 mmHg (adjusted OR 57.87, 95% CI 5.08-658.96). Absent
      vibratory sensation and low ankle-arm blood pressure index were not significant
      independent risk factors. CONCLUSIONS: Both neuropathy and vasculopathy are
      strong independent risk factors for the development of diabetic foot ulcers. In
      our model, the strongest risk factor is impaired cutaneous oxygenation. However,
      in the clinical setting, sensory examination with a 5.07 monofilament probably
      remains the single most practical measure of risk assessment.

PMID- 7729301
TI  - Sex differences in insulin levels in older adults and the effect of body size,
      estrogen replacement therapy, and glucose tolerance status. The Rancho Bernardo
      Study, 1984-1987.
AB  - OBJECTIVE--To determine if insulin levels vary with sex, independent of estrogen
      replacement therapy (ERT), differences in body mass index (BMI), waist-to-hip
      ratio (WHR), and glycemia. RESEARCH DESIGN AND METHODS--In a population-based
      study of older adults, insulin levels were measured before and after a
      standardized oral glucose tolerance test in 673 men and 849 women, all free of
      known diabetes. RESULTS--Age-adjusted fasting insulin levels were highest in men,
      intermediate in women not taking estrogen, and lowest in estrogen-treated women
      (P < 0.01). Differences between men and women not taking estrogen disappeared
      after adjusting for age and BMI, but not glycemia; estrogen-treated women had
      significantly lower fasting insulin levels than did men (P < 0.01) and women not
      taking estrogen (P < 0.01). The association of estrogen use with lower fasting
      insulin levels persisted after adjusting for age and WHR (P < 0.001) and was
      stronger among women with abnormal glucose tolerance. Age-adjusted postchallenge
      insulin levels were higher in women than in men (P < 0.01). The sex difference
      persisted after adjusting for age and BMI or glycemia. Postchallenge insulin
      levels did not vary by ERT. CONCLUSIONS--Men have higher fasting insulin levels
      than do women, whether or not the women are using ERT. Differences between men
      and untreated women are explained by differences in BMI, but estrogen users have
      lower fasting insulin levels independent of BMI. Postchallenge insulin levels are
      higher in women than men and are independent of ERT, BMI, and glycemia. Clinical
      trials in women are needed to determine whether ERT can improve insulin and
      glucose metabolism.

PMID- 7729302
TI  - Circulating endothelin-1 levels increase during euglycemic hyperinsulinemic clamp
      in lean NIDDM men.
AB  - OBJECTIVE: To evaluate whether or not insulin stimulates endothelin (ET)-1
      secretion in vivo. RESEARCH DESIGN AND METHODS: Plasma ET-1 levels were evaluated
      in 16 lean normotensive men with non-insulin-dependent diabetes mellitus (NIDDM)
      (mean age 50.3 +/- 4.1 years) during either a 2-h euglycemic hyperinsulinemic
      clamp (40 mU insulin.m-2.min-1) or placebo infusion (50 ml isotonic saline)
      according to a single-blind randomized crossover protocol. RESULTS: Circulating
      ET-1 levels increased during the euglycemic hyperinsulinemic clamp (from 0.88 +/-
      0.38 pg/ml at time 0 to 1.66 +/- 0.22 pg/ml and 1.89 +/- 0.99 pg/ml at 60 and 120
      min, respectively [P < 0.05 vs. time 0]) and returned to baseline levels after
      the discontinuation of insulin infusion (0.71 +/- 0.22 pg/ml after a 30-min
      period of recovery [NS]). Compared with placebo, the euglycemic hyperinsulinemic
      clamp induced a significant increase in plasma ET-1 levels at 60 min (P < 0.0001)
      and 120 min (P < 0.0001). Changes in basal insulin levels and corresponding
      changes in circulating ET-1 levels after a 2-h euglycemic hyperinsulinemic clamp
      were significantly correlated (r = 0.771, P < 0.0001). A possible unfavorable
      effect of ET-1 on the tissue sensitivity to insulin-stimulated glucose uptake was
      suggested by the presence of a negative correlation between total glucose uptake
      and baseline ET-1 levels (r = -0.498, P < 0.05). CONCLUSIONS: Our findings
      indicate that circulating ET-1 levels significantly increase during euglycemic
      hyperinsulinemic clamp in men with NIDDM. The negative correlation between total
      glucose uptake and circulating ET-1 levels suggests that the peptide might exert
      negative effects on the insulin sensitivity of target tissues. The consequent
      increase in insulin secretion as well as the insulin-related ET-1 release from
      endothelial cells could favor the development of diabetes-related vascular
      lesions.

PMID- 7729303
TI  - Independent correlation between plasma lipoprotein(a) and angiographic coronary
      artery disease in NIDDM.
AB  - OBJECTIVE: To examine the correlation between angiographic coronary artery
      disease (CAD) and plasma lipoprotein(a) [Lp(a)] concentration in non-insulin
      dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: In this cross
      sectional study of 36 patients with NIDDM who underwent coronary angiography, CAD
      was assessed visually using a coronary artery score (CAS), and plasma Lp(a) was
      measured immunoturbidimetrically. RESULTS: Lp(a) concentration was significantly
      higher in patients in the middle and upper tertiles of CASs (> 4) compared with
      those in the lower tertile (< or = 4); geometric mean 0.30 g/l (95% confidence
      interval [CI] 0.22-0.40) vs. 0.12 g/l (0.08-0.17, P = 0.002). Lp(a) was
      significantly and positively correlated with the CAS (R2 23%, P = 0.006),
      independent of other cardiovascular risk factors, including lipoprotein related
      variables and glycated hemoglobin. CONCLUSIONS: Plasma Lp(a) is a strong and
      independent correlate of the extent of angiographic CAD in symptomatic patients
      with NIDDM.

PMID- 7729304
TI  - Digoxin does not accelerate progression of diabetic retinopathy.
AB  - OBJECTIVE: To test the hypothesis that digoxin, an inhibitor of Na(+)-K(+)-ATPase
      activity, accelerates the progression of diabetic retinopathy. RESEARCH DESIGN
      AND METHODS: We compared the incidence and risk of retinopathy in 120 digoxin
      taking vs. 867 non-digoxin-taking diabetic participants in the Wisconsin
      Epidemiologic Study of Diabetic Retinopathy (WESDR) and in 117 digoxin-taking vs.
      1,883 non-digoxin-taking diabetic subjects in the Early Treatment Diabetic
      Retinopathy Study (ETDRS). In both studies, retinopathy was detected by grading
      stereoscopic color photographs using the modified Airlie House classification
      scheme, and a two-step difference in baseline retinopathy grade was considered
      significant. RESULTS: After controlling for other risk factors, we found no
      statistically significant association with either 4-year incidence of retinopathy
      (WESDR) or progression of retinopathy (WESDR and ETDRS) in patients taking
      digoxin at baseline compared with those not taking digoxin. CONCLUSIONS: These
      data suggest that digoxin therapy does not adversely affect the course of
      diabetic retinopathy.

PMID- 7729305
TI  - Prospective study of lipoprotein(a) as a risk factor for atherosclerotic
      cardiovascular disease in patients with diabetes.
AB  - OBJECTIVE: To assess whether lipoprotein(a) [Lp(a)] is a risk factor for
      atherosclerotic cardiovascular disease in diabetes. RESEARCH DESIGN AND METHODS:
      We studied 221 patients with non-insulin-dependent diabetes mellitus (NIDDM)
      without diabetic complications who were followed for 2.2-3.1 years. Their serum
      Lp(a) levels were semiquantified by a rapid electrophoretic method that
      accurately discriminates high from low serum Lp(a) at the 20 mg/dl level.
      RESULTS: Seven of 105 diabetic patients with a high serum Lp(a) experienced a
      clinical event related to atherosclerotic cardiovascular disease. This incidence
      was significantly higher than that of the 110 diabetic patients with a low serum
      Lp(a). The logistic regression analysis revealed that Lp(a) was an independent
      risk factor for the event. CONCLUSIONS: Lp(a) is a significant risk factor for
      atherosclerotic cardiovascular disease in NIDDM.

PMID- 7729306
TI  - The use of areas under curves in diabetes research.
AB  - Recently, several articles appearing in the diabetes literature have suggested
      that many investigators are unclear about a number of issues involving the use of
      areas under the curve (AUCs). This prompted us to reconsider issues in the
      calculation, use, meaning, and presentation of AUCs. We discuss five issues: 1)
      What is a curve and an area? 2) How should one graphically present a group's
      curve? 3) How should one calculate AUCs? 4) Should one subtract baseline values
      from outcome values before calculating AUCs? And 5) are AUCs the best way to
      combine multiple readings into a single index?

PMID- 7729307
TI  - Inferences and implications. Do results from the Diabetes Control and
      Complications Trial apply in NIDDM?

PMID- 7729308
TI  - Hyperglycemia and microvascular and macrovascular disease in diabetes.
AB  - In summary, over the past 16 years, since the publication of Kelly West's book,
      epidemiological study has provided better insight into the relation of
      hyperglycemia and diabetic complications. Data from the WESDR demonstrate a
      strong consistent relationship between hyperglycemia and the incidence and
      progression of microvascular (diabetic retinopathy, loss of vision, and
      nephropathy) and macrovascular (amputation and cardiovascular disease mortality)
      complications in people with IDDM and NIDDM (Figs. 19 and 20). The DCCT has
      demonstrated that intensive insulin therapy will reduce the incidence and
      progression of microvascular complications in people with IDDM (22). A number of
      further challenges await laboratory scientists and epidemiologists regarding
      hyperglycemia in people with diabetes. There is a need to understand the relation
      of hyperglycemia to pathogenetic mechanisms that lead to the development of
      specific complications, to develop new methods to detect and physiologically
      treat hyperglycemia, and to develop better methods of primary and secondary
      prevention of diabetic complications in people with IDDM and NIDDM.

PMID- 7729309
TI  - Glutamic acid decarboxylase antibodies and diabetes complications. Assay
      reliability and validity.

PMID- 7729310
TI  - Differential response of plasma lipoprotein(a) and apolipoprotein B in NIDDM
      subjects treated with acarbose.

PMID- 7729311
TI  - Insulin sensitivity and mitochondrial gene mutation.

PMID- 7729312
TI  - QT interval in diabetic patients with cardiac autonomic neuropathy.

PMID- 7729313
TI  - Malnutrition-related diabetes mellitus (MRDM), not diabetes-related malnutrition.
      A report on genuine MRDM.

PMID- 7729314
TI  - An easy sliding scale formula.

PMID- 7729315
TI  - Adrenal androgens and NIDDM.

PMID- 7729316
TI  - Providing pain control for the critically ill substance-abuse patient.

PMID- 7729317
TI  - Third generation antitachycardia pacing implantable cardioverter-defibrillators.
AB  - With advanced third-generation implantable cardioverter-defibrillator (ICD)
      technology, patients receiving electrical therapy may only be aware of symptoms
      such as palpitations, or may be completely unaware of the event. Third-generation
      ICDs provide bradycardia back-up pacing, antitachycardia pacing (ATP),
      cardioversion, and defibrillation therapy. Additional benefits are noninvasive
      electrophysiologic testing capabilities and enhanced diagnostic features. An
      alternative surgical approach with a nonthoracotomy lead system is now also
      available.

PMID- 7729318
TI  - The closed tracheal suction system: implications for critical care nursing.
AB  - The Closed Tracheal Suction System (CTSS) is a multiple-use suction catheter
      available for suctioning the ventilator dependent patient. While research has
      been reported on its impact on oxygen desaturation, ventilator function, and
      nosocomial pneumonia, the practical issues of the technical design of the
      catheter and its advantage in decreasing exposure of staff to infected
      respiratory secretions have not been investigated. This study reports the
      critical care nurses' perceptions in the use of the SteriCath (Concord/Portex)
      CTSS focusing on hemodynamic stability, effectiveness of suctioning, patient
      safety and staff personnel exposure.

PMID- 7729319
TI  - Amiodarone pulmonary toxicity: the nursing challenge.
AB  - A common therapy for patients with uncontrolled ventricular arrhythmias requires
      the critical care nurse to perform ongoing assessment for prevention of and
      intervention for complications.

PMID- 7729320
TI  - Preventing complications in double-lumen endotracheal tubes with independent lung
      ventilation.
AB  - The double lumen endotracheal tube is a familiar device that has recently
      acquired a new application. This article describes how double-lumen endotracheal
      tubes are used for independent lung ventilation in the treatment of unilateral
      lung disease, and how the critical care nurse can prevent complications during
      their use.

PMID- 7729321
TI  - Expanding the use of critical pathways in critical care.
AB  - Critical pathways are known to decrease the patient's length of stay while
      simultaneously using resources effectively and efficiently. Several additional
      functions of critical pathways exist: pathways are used as tools for teaching; to
      predict and prevent complications; streamline charting; and anticipate staffing
      needs. These and other functions of critical pathways are described as they apply
      to critical care patients.

PMID- 7729322
TI  - Marketing critical pathways in critical care.

PMID- 7729323
TI  - Strategies for motivating CCU patients.
AB  - Changes in health care delivery have led to shorter hospital stays for sicker
      patients. These factors require the critical care nurse to become involved in
      rehabilitation. Cardiac patients, once stable, begin the cardiac rehabilitation
      program while in critical or intermediate care. This article discusses ways in
      which critical care nurses improve the motivation of medical and surgical
      patients with cardiac conditions to participate in cardiac rehabilitation.

PMID- 7729324
TI  - Nicotine treatment in ulcerative colitis. Current status.

PMID- 7729325
TI  - Goals of antihypertensive therapy.
AB  - Antihypertensive therapy has been used for almost 40 years to reduce blood
      pressure and to prevent morbidity and mortality related to the hypertensive
      state. Cardiovascular events are related to the initial elevation of blood
      pressure; the benefits of treating malignant, severe or moderate hypertension are
      well established. Although large scale clinical trials have demonstrated a
      decrease in morbid events when mildly elevated blood pressures is treated, the
      benefits are neither universal or dramatic and treatment is certainly less cost
      effective than no treatment. Recently it has been emphasised that the absolute
      risk of cardiovascular events is determined only in part by blood pressure, and
      that it is also influenced by age, gender, race and the presence of other
      cardiovascular risk factors. For example, in older individuals where the absolute
      risk of vascular complications is greater than in younger individuals for any
      given level of blood pressure, the benefits of therapy will be greater. It has
      been suggested that in younger individuals with mild hypertension and a low
      absolute risk of developing cardiovascular morbid events it may be more
      appropriate to monitor the effects of drug therapy on measures of cardiac and
      vascular damage that are associated with the hypertensive state. Drug therapy has
      been shown to be extremely effective in reducing the incidence of stroke,
      congestive cardiac failure and renal failure associated with elevated blood
      pressure. Meta-analysis of randomised large scale clinical trials indicates that
      drug therapy may not reduce coronary events to the extent expected in patients
      with hypertension. One plausible explanation is that the trials have been of
      insufficient duration to detect the benefit of blood pressure lowering on
      coronary heart disease. It has also been suggested that certain adverse metabolic
      effects associated with the use of thiazide diuretics and beta-blockers employed
      in these trials may have partially offset the benefits of blood pressure
      reduction. However, the clinical significance of these drug-induced metabolic
      disturbances remains unclear. Experimental data suggesting differences in the
      ability of antihypertensive drugs to inhibit atherosclerosis in animal models are
      also of interest, but again the relation of the findings to the clinical
      situation is unknown. Thiazide diuretics, beta-blockers, calcium antagonists,
      angiotensin-converting enzyme (ACE) inhibitors and alpha-blockers can produce
      regression of left ventricular hypertrophy (LVH). While LVH is clearly a strong
      and independent predictor for coronary disease, it remains to be shown that a
      lower risk for coronary morbid events exists in patients whose LVH has undergone
      regression over and above that attributable to blood pressure reduction.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7729326
TI  - Daily life cardiac ischaemia. Should it be treated?
AB  - Daily life cardiac ischaemia is defined as reversible myocardial cellular hypoxia
      that occurs during activities of daily living, without artificial provocation.
      Most of these daily life ischaemic episodes are not associated with symptoms.
      However, it is not practical to distinguish silent versus symptomatic daily life
      ischaemia as both are associated with haemodynamic abnormalities and future
      adverse outcomes. Daily life cardiac ischaemia is best detected using ambulatory
      electrocardiogram (ECG) monitoring; however, there are other diagnostic tools
      (e.g. exercise treadmill) that can be used. Once detected, the optimal therapy
      for daily life myocardial ischaemia has yet to be identified. However, it does
      appear that usual antianginal medications including nitrates, beta-blockers,
      calcium antagonists and antiplatelet drugs are effective in reducing the
      incidence and severity of daily life myocardial ischaemia. Medical therapy and
      revascularisation should be utilised to obliterate all episodes of daily life
      cardiac ischaemia to prevent future cardiac events. Moreover, the efficacy of the
      chosen therapeutic regimen for each patient should be documented with follow-up
      objective testing. The diagnosis and management of daily life myocardial
      ischaemia is continually evolving. Future research as well as economic
      considerations will shape future management strategies.

PMID- 7729327
TI  - Nitrate tolerance in angina therapy. How to avoid it.
AB  - Tolerance is the attenuation, or loss, of one or several of the effects of
      organic nitrates after long term administration. All organic nitrate regimens
      using frequent doses of long-acting nitrates (3 or more times daily), continuous
      delivery systems [transdermal nitroglycerin (glyceryl trinitrate) patches or
      continuous intravenous infusions of nitroglycerin] or long-acting (sustained
      release) preparations will result in partial or complete nitrate tolerance. There
      are several proposed mechanisms which may contribute to the development of
      tolerance including activation of neurohormonal mechanisms, plasma volume
      expansion and depletion of intracellular sulfhydryl cofactors. To avoid tolerance
      to long term nitrate therapy, regimens should be tailored to provide a 10- to 12
      hour nitrate-free interval when possible. This means that antianginal prophylaxis
      can only be provided by nitrate therapy for some portion of each day, and that
      some patients will develop an increase in angina in the nitrate-free intervals
      which will necessitate short term therapy with sublingual nitroglycerin or a
      similar preparation.

PMID- 7729328
TI  - Multiple sclerosis therapy. A practical guide.
AB  - A growing amount of evidence suggests that a disturbance of immunological
      function is of importance in the pathogenesis of multiple sclerosis. This is
      reflected in the drugs used to slow progression and to treat relapses.
      Immunosuppressive drugs such as azathioprine, cyclophosphamide and cyclosporin
      might have some potential to slow down progression of multiple sclerosis, but
      their use is limited by potentially serious adverse effects. Recently, it was
      shown that interferon-beta-1b can diminish the exacerbation rate in multiple
      sclerosis without leading to unacceptable adverse effects. Nevertheless,
      symptomatic treatment remains of crucial importance in the management of multiple
      sclerosis patients. Spasticity, depression, fatigue and urinary, paroxysmal and
      sensory symptoms can all be alleviated to some extent with pharmacological
      interventions, although rehabilitation procedures and psychosocial consultations
      are no less important. Further therapeutic approaches to multiple sclerosis will
      be directed at either the specificity of the immune response or the grade of
      activation of the immune response. Magnetic resonance imaging techniques will
      play an important role in the evaluation of efficacy of new therapeutic agents.

PMID- 7729329
TI  - The diagnosis and management of uveitis.
AB  - The diagnosis and management of uveitis is complicated and challenging. The
      protean signs and symptoms seen in patients with uveitis may lead to a diagnostic
      dilemma. A carefully taken history with particular attention to demographic
      factors and meticulous physical examination are crucial to guiding diagnostic
      testing. Tailoring the diagnostic approach in patients with uveitis frequently
      yields useful data in contrast to blanketing every possible uveitic entity. It is
      also important to distinguish among various aetiologies, including infectious and
      neoplastic causes which may respond to specific therapy. Medical treatment of
      noninfectious uveitis must have clear objectives including reduction of
      inflammation, relief of symptoms and restoration of visual functioning.
      Familiarity with possible symptoms and signs of adverse drug reactions is
      essential early in the course of treatment so that their effects may be
      minimised. Appropriate therapy of presumed autoimmune uveitis is based on disease
      severity, presence or absence of bilateral disease and the health status of the
      patient.

PMID- 7729330
TI  - Prescribing oral contraceptives.
AB  - The combined oral contraceptive pill is the most popular method of contraception
      worldwide, with modern low-dose formulations significantly improving
      tolerability. Breakthrough bleeding is the most significant adverse event
      associated with the low-dose combined oral contraceptives. Monophasic, biphasic,
      triphasic and progestogen-only preparations are available, and the choice of
      formulation should be tailored to best suit the patient. Any areas of uncertainty
      or concern that the patient has should be addressed, and the patient should be
      clearly informed of how to use the oral contraceptive effectively, the likely
      initial adverse effects and what to do if a pill is missed.

PMID- 7729332
TI  - Cabergoline. A review of its pharmacological properties and therapeutic potential
      in the treatment of hyperprolactinaemia and inhibition of lactation.
AB  - Cabergoline is a synthetic ergoline which shows high specificity and affinity for
      the dopamine D2 receptor. It is a potent and very long-acting inhibitor of
      prolactin secretion. Prolactin-lowering effects occur rapidly and, after a single
      dose, were evident at the end of follow up (21 days) in puerperal women, and up
      to 14 days in patients with hyperprolactinaemia. In the only comparative study to
      date, cabergoline 0.5 to 1.0 mg twice weekly was more effective than
      bromocriptine 2.5 to 5.0 mg twice daily in the treatment of hyperprolactinaemic
      amenorrhoea, restoring ovulatory cycles in 72% of women and normalising plasma
      prolactin levels in 83%, compared with 52 and 58%, respectively, for
      bromocriptine. In the prevention of puerperal lactation, a single dose of
      cabergoline 1.0mg was as effective as bromocriptine 2.5mg twice daily for 14
      days. A significantly lower incidence of rebound lactation in the third
      postpartum week was seen with cabergoline. Unpublished data suggest cabergoline
      0.25mg twice daily for 2 days is effective in suppressing established puerperal
      lactation in about 85% of women. Nausea, vomiting, headache and dizziness are
      characteristic adverse events of the dopaminergic ergot derivatives. Cabergoline
      appears to be better tolerated than bromocriptine in both patients with
      hyperprolactinaemia and postpartum women. Most patients intolerant of other ergot
      derivatives can tolerate cabergoline. Bromocriptine use in the puerperium has
      been associated with an increased risk of serious thromboembolic events. However,
      there are no such reports with cabergoline and whether these events will become
      associated with other dopaminergic agents is unknown. The teratogenic potential
      of cabergoline has not been extensively investigated in humans. Ten congenital
      abnormalities have been reported in 199 cabergoline-associated pregnancies.
      Although there is no pattern to these abnormalities, the limited experience with
      cabergoline in pregnancy means the drug cannot be considered as a first-line
      therapy for the treatment of infertility associated with hyperprolactinaemia. At
      this stage of its development, cabergoline will prove useful in patients with
      hyperprolactinaemia who have failed treatment with, or are intolerant of, other
      dopamine agonists such as bromocriptine. If drug treatment is required for the
      prevention or suppression of puerperal lactation, cabergoline offers significant
      advantages over bromocriptine and should become the drug treatment of first
      choice for this indication.

PMID- 7729331
TI  - Epoetin alfa. A review of its pharmacodynamic and pharmacokinetic properties and
      therapeutic use in nonrenal applications.
AB  - Epoetin alfa is a recombinant form of the principal hormone responsible for
      erythrogenesis, erythropoietin. Already an established treatment for anaemia
      associated with renal failure, epoetin alfa may also be used to correct anaemia
      in other patient groups. The drug increases the capacity for autologous blood
      donation in patients scheduled to undergo surgery and attenuates the decrease in
      haematocrit often seen in untreated autologous donors. However, transfusion
      requirements did not significantly decrease in many trials. Epoetin alfa also
      accelerates red blood cell recovery after allogeneic--but not autologous--bone
      marrow transplant. Limited data in patients with adult rheumatoid arthritis
      suggest that while epoetin alfa increases haematocrit/haemoglobin levels, overall
      clinical rheumatological status may not improve. However, the drug did improve
      quality of life in a small cohort of children with juvenile rheumatoid arthritis
      in addition to correcting anaemia. Response rates to treatment with epoetin alfa
      in patients with anaemia associated with cancer range between 32 and 85%. Anaemia
      associated with cancer chemotherapy also responds well to treatment with the drug
      as does anaemia associated with zidovudine therapy in patients with acquired
      immune deficiency syndrome (AIDS). Studies evaluating the use of epoetin alfa as
      treatment for anaemia of prematurity have used different methodologies and
      dosages, making overall analysis difficult. Nevertheless, it appears that high
      dosages are necessary for response. Results from 1 study suggest that treatment
      with epoetin alfa appears to be more costly than transfusional support in this
      application; the relevance of this finding is questionable, however, given that
      the aim of treatment with epoetin alfa is elimination of transfusion
      requirements. The incidence of many adverse events associated with epoetin alfa
      treatment in patients with renal failure (hypertension, seizures and
      thromboembolic events) has been minimal in patients without renal failure.
      Adverse events occurred at a similar rate in placebo and epoetin alfa recipients
      in placebo-controlled trials evaluating the use of the drug as treatment for
      anaemia in patients with cancer receiving chemotherapy or patients with AIDS
      receiving zidovudine. In summary, epoetin alfa is an effective alternative to
      blood transfusion, reducing anaemia and producing consequent improvements in
      quality of life in many nonrenal applications. It was more effective than placebo
      in a number of double-blind trials and may be particularly useful as treatment
      for anaemia associated with other drugs such as cisplatin and zidovudine.

PMID- 7729333
TI  - Venlafaxine. A review of its pharmacology and therapeutic potential in
      depression.
AB  - Venlafaxine is a phenylethylamine derivative which facilitates neurotransmission
      in the brain by blocking presynaptic reuptake of serotonin (5-hydroxytryptamine:
      5-HT) and noradrenaline (norepinephrine). Clinical data from patients with major
      depression are consistent with the favourable efficacy and tolerability profile
      of venlafaxine predicted by pharmacodynamic studies. In patients with major
      depression, venlafaxine 75 to 375 mg/day administered for 6 weeks was
      significantly more effective than placebo, and at least as effective as
      imipramine, clomipramine, trazodone or fluoxetine. Venlafaxine is well tolerated,
      being associated with fewer anticholinergic and CNS adverse effects than
      tricyclic antidepressants. Unlike the tricyclic antidepressants, venlafaxine does
      not appear to significantly affect cardiac conduction, although there have been a
      few reports of modest increases in blood pressure, particularly after high doses
      of the drug. In conclusion, wider clinical experience is required to better
      characterise and confirm potential advantages of venlafaxine compared with other
      antidepressant agents. These advantages may include a rapid onset of action and
      reduced propensity to cause anticholinergic effects and cardiotoxicity compared
      with tricyclic antidepressants. Nevertheless, at this stage venlafaxine offers a
      more attractive treatment option than tricyclic antidepressants for patients with
      major depression, primarily because of its good overall tolerability profile.

PMID- 7729334
TI  - Hearing results in tympanoplasty.

PMID- 7729335
TI  - Temporal bone fracture with dislocation of the incus.

PMID- 7729336
TI  - The use of an adenoid punch in endoscopic intranasal surgery.

PMID- 7729337
TI  - Subtle submucosal hemorrhage causing dysphonia.

PMID- 7729338
TI  - How may I shorten your nose? Let me count the ways.

PMID- 7729339
TI  - Hearing results of surgery for acquired cholesteatoma.
AB  - Hearing results in 349 chronic ears with cholesteatoma were evaluated. The great
      majority of the patients underwent canal wall-down mastoidectomy as a one-stage
      procedure. After a mean follow-up period of 7.3 years, 35% of the ears operated
      on showed hearing levels of 30 dB or better. Hearing improved in 30%, remained
      unchanged in 55%, and worsened in 15%. The mean hearing gain was only 5 dB. In
      23% of ears with otherwise successful outcomes the tympanum turned fibrotic,
      leading to poor hearing function.

PMID- 7729340
TI  - Hearing results of surgery for chronic otitis media without cholesteatoma.
AB  - Hearing results after surgical treatment for chronic otitis media were evaluated
      in 569 patients. Cases of cholesteatoma were excluded. The mean follow-up period
      was 5.2 years. Ears with intact ossicular chain showed best postoperative hearing
      function. Satisfactory hearing results were obtained in 68% of ears with eroded
      ossicles but intact stapes and in only 50% of ears with loss of stapes
      superstructure. Cases of sequelae to otitis showed better hearing results than
      cases of granulating otitis media. At last follow-up examination, 72 percent of
      the whole series had hearing levels of 30 dB or better.

PMID- 7729341
TI  - How a labyrinthine fistula may sometimes be useful for surgery.
AB  - The author reports a case of chronic otitis with cholesteatoma complicated by a
      fistula of the lateral semicircular canal and a stapedo-ovalar ankylosis,
      probably of otosclerotic origin, in which the decision to take advantage of the
      fistula to create conditions similar to those generally produced by labyrinthine
      fenestration allowed virtual functional recovery of the patient's hearing. The
      case illustrates how, with a ploy of this kind, certain intrinsically negative
      features may actually turn out to be a blessing in disguise.

PMID- 7729342
TI  - Cysticercosis of the tongue.
AB  - A 10-year-old Hindu boy had a gradually increasing swelling on the tongue, which
      was excised and diagnosed histopathologically as a case of cysticercosis.
      Involvement of the tongue as an isolated lesion has prompted us to present this
      case. A review on the subject is discussed.

PMID- 7729343
TI  - Cylindrical cell papilloma of the nasal septum.
AB  - Papillomas of the sinonasal tract are uncommon tumors. They can be subdivided
      into different histopathological entities including inverting papilloma,
      fungiform papilloma and cylindrical cell papilloma. Cylindrical cell papilloma is
      one of the rarest with only twenty-three cases reported. This rare histologically
      distinct variant of papillomas of the sinonasal tract behaves clinically like
      inverting papillomas. We present what we believe to be the first reported case of
      a cylindrical cell papilloma isolated to the nasal septum. The patient's
      pathology and a literature review of cylindrical cell papillomas of the sinonasal
      tract are presented.

PMID- 7729344
TI  - Blindness secondary to injections in the nose, mouth, and face: cause and
      prevention.
AB  - The potential hazard of blindness from injections in the face, nose, and mouth
      and the mechanisms by which this complication takes place are discussed.
      Precautionary measures, which we originally recommended for nasal turbinate
      injections, appear to be applicable for all injections in this area. We encourage
      their usage.

PMID- 7729345
TI  - Extrinsic tracheal compression--a newly described complication of acquired immune
      deficiency syndrome (AIDS).
AB  - An AIDS patient was seen in respiratory difficulty with a superior mediastinal
      mass. Examination revealed a candida fungoma. To the best of our knowledge, this
      is the only case of its nature. The differential diagnosis and management of this
      patient are presented in detail.

PMID- 7729346
TI  - Assessment of cortical motor output: compound muscle action potential versus
      twitch force recording.
AB  - To determine whether motor evoked potential (MEP) amplitude and area are accurate
      measurements of the magnitude of response to magnetic cortical stimulation, we
      simultaneously recorded the twitch and MEP in the first dorsal interosseous
      muscle of 8 normal subjects. Consecutive stimuli were delivered at increasing
      stimulus intensities (SI) or with increasing levels of background voluntary
      muscle contraction (BVC). There was stimulus to stimulus variability in MEP
      amplitude, area and twitch force. At low SI and at low levels of background
      contraction, there was a good correlation between twitch amplitude and MEP
      amplitude and area (r = 0.6-0.96, P < 0.005). Increasing either variable caused
      the correlation to decrease significantly (r = 0.02-0.31, P > 0.01). With
      increasing SI, MEP amplitude and area plateaued but twitch force continued to
      increase. A similar pattern was observed with higher levels of background muscle
      contraction although in some subjects a second increase in MEP amplitude and area
      was seen. Collision experiments demonstrated that the amplitude of the EMG
      activity resulting from repetitive motoneuron firing increased as SI was
      increased. This is due to multiple descending volleys which result in repetitive
      firing of some spinal motoneurons. Rapid, repetitive firing of some motor units
      is likely to result in phase cancellation and, therefore, the MEP amplitude, and
      to a lesser extent area, do not accurately reflect the net motor output.

PMID- 7729347
TI  - [Good usage of antidepressants. Proceedings of a meeting. Laguiole, 10-12 June
      1994].

PMID- 7729348
TI  - [Cognitive effects of chronic antidepressant treatment].

PMID- 7729349
TI  - [Co-prescription with a given antidepressant: empirical or rational treatment?].

PMID- 7729350
TI  - [What are the severity criteria in depressive disorder?].

PMID- 7729351
TI  - [Evaluation studies on the efficacy of an antidepressant drug].

PMID- 7729352
TI  - [Behavior of 5-HT receptors during long-term antidepressant treatment and at
      discontinuation].

PMID- 7729353
TI  - [The viewpoint of the psychiatrist on patient outcome after discontinuation of
      antidepressant treatment].

PMID- 7729354
TI  - [Orientations regarding psychotherapy treatment for depressive states].

PMID- 7729355
TI  - [Dimensional approach to trans-nosographic study of psychotropic drugs].

PMID- 7729356
TI  - [Borderline states: intermittent antidepressants or long-term course?].

PMID- 7729357
TI  - [Schizophrenia: value and limits of antidepressant drugs].

PMID- 7729358
TI  - [Use of antidepressants in elderly subjects: justifications and risks].

PMID- 7729359
TI  - [When discontinue preventive treatment of recurrent depression?].

PMID- 7729360
TI  - [Dependence on antidepressive agents: an authentic addiction?].

PMID- 7729361
TI  - [New approaches to cognitive psychophysiology in psychiatry: the example of
      depression].

PMID- 7729362
TI  - Functional imaging of the brain using superconducting magnetometry.
AB  - Magnetoencephalography (MEG) is the measurement of the weak magnetic fields
      generated by neuronal activity in the human brain. By measuring the magnetic
      field evoked when specific sensory stimuli are presented to a subject, a map of
      the functional organization of the brain can be deduced with a subcentimetre
      spatial resolution and a millisecond temporal resolution. As well as a tool for
      fundamental study of the brain, MEG can also be used in clinical studies and
      assessment of patients with specific neurological disorders.

PMID- 7729363
TI  - Low temperature optical absorption spectroscopy: an approach to the study of
      stereodynamic properties of hemeproteins.
AB  - In this short review we show how suitable analysis of the temperature dependence
      of the optical absorption spectra of metalloproteins can give insight into their
      stereodynamic properties in the region of the chromophore. To this end, the
      theory of coupling between an intense allowed electronic transition of a
      chromophore and Franck-Condon active vibrations of the nearby atoms is applied to
      the Soret band of hemeproteins to obtain an analytical expression suitable for
      fitting the spectral profile at various temperatures. The reported approach
      enables one to separate the various contributions to the overall bandwidth
      together with the parameters that characterize the vibrational coupling. The
      thermal behavior of these quantities gives information on the dynamic properties
      of the active site and on their dependence upon protein structure and ligation
      state. The Soret band of hemeproteins appears to be coupled to high frequency
      vibrational modes of the heme group (as already shown by resonance Raman
      spectroscopy) and to a "bath" of low frequency modes most likely deriving from
      the bulk of the protein. For the deoxy derivatives inhomogeneous broadening
      arising from conformational heterogeneity appears to contribute substantially to
      the linewidth. The data indicate the onset, at temperatures near 180 K, of large
      scale anharmonic motions that can be attributed to jumping among different
      conformational substates of the protein.

PMID- 7729364
TI  - Molecular dynamics simulations of excimer forming (+)-anti-BPDE-DNA adducts in
      aqueous solution.
AB  - The chemical carcinogen (+)-anti BPDE preferentially binds covalently to the
      guanine base in the minor groove of DNA. Fluorescence spectroscopic studies have
      shown that the BPDE molecules bound to DNA can interact in their photo-excited
      state giving strong excimer fluorescence when bound to poly(dGdC).poly(dGdC). It
      was suggested that the formation of such excited state complexes is most probable
      when the two (+)-anti-BPDE bind to guanines of adjacent base pairs on the two
      different strands of the DNA. In the present work a model for such an excimer
      forming DNA-BPDE double adduct system has been constructed and shown to be stable
      over a 300 ps molecular dynamics simulation in a water box. The model is a
      d(CG)3.d(CG)3 molecule with two BPDE molecules bound to the guanines at the 4th
      position on each strand, located in the minor groove and each oriented towards
      the 5' end of the modified strand, respectively. The results of 300 ps MD
      simulation show that the two BPDE chromophores exhibited on the average a
      relative geometry favourable for excimer formation. The local structure at the
      adduct position was considerably distorted and the helix axis was bent. The
      modified bases were found to be paired through a stable single non-Watson Crick
      type of hydrogen bond.

PMID- 7729365
TI  - Dynamics of the peptide hormone motilin studied by time resolved fluorescence
      spectroscopy.
AB  - Time resolved fluorescence was used to study the dynamics on the nanosecond and
      subnanosecond time scale of the peptide hormone motilin. The peptide is composed
      of 22 amino acid residues and has one tyrosine residue in position 7, which was
      used as an intrinsic fluorescence probe. The measurements show that two
      rotational correlation times, decreasing with increasing temperature, are needed
      to account for the fluorescence polarization anisotropy decay data. Viscosity
      measurements combined with the fluorescence measurements show that the rotational
      correlation times vary approximately as viscosity with temperature. The shorter
      rotational correlation time (0.08 ns in an aqueous solution with 30%
      hexafluoropropanol, HFP at 20 degrees C) should be related to internal movement
      of the tyrosine side chain in the peptide while the longer rotational correlation
      time (2.2 ns in 30% HFP at 20 degrees C) describes the motion of the whole
      peptide. In addition, the interaction of motilin or the derivative motilin (Y7F) 
      23W (with tyrosine substituted by phenylalanine and with a tryptophan fluorophore
      added to the C-terminal) with negatively charged phospholipid vesicles (DOPG) was
      studied. The results show the development of a long anisotropy decay time which
      reflects partial immobilization of the peptide by interaction with the vesicles.

PMID- 7729366
TI  - Investigation of ion binding to the cytoplasmic binding sites of the Na,K-pump.
AB  - A dual-wavelength fluorimeter was constructed, which used two light emitting
      diodes (LEDs) to excite the fluorescence dye RH 421 alternately with two
      different wavelengths. The ratio of the emissions at the two excitation
      wavelengths provided a drift-insensitive signal, which allowed detection of very
      small changes of the fluorescence intensity. Those small changes were induced by
      ion binding and release in conformation E1 of the Na,K-ATPase. Titration
      experiments were performed to determine equilibrium dissociation constants (+/-
      standard deviation) for each step in the complete binding and release sequence:
      0.12 +/- 0.01 mM (E2(K2)<==>KE1), 0.08 +/- 0.01 mM (KE1<==>E1A), 3.0 +/- 0.2 mM
      (NaE1<==>E1), 5.2 +/- 0.4 mM (Na2E1<==>NaE1) and 6.5 +/- 0.4 mM (Na3E1<==>Na2E1)
      at pH 7.2 and T = 16 degrees C. These numbers show that the affinities of the
      binding sites exposed to the cytoplasm, are higher for K+ than for Na+ ions,
      similar to what was found on the extracellular side. The physiological
      requirement for extrusion of Na+ from the cytoplasm, and for import of K+ from
      the extracellular medium seems to be facilitated not by favorable binding
      affinities in state E1 but by the two ATP-driven reaction steps of the cycle,
      E2(K2) + ATP-->K2E1.ATP and Na3E1.ATP<==>(Na3) E1-P, which border the ion
      exchange reactions at the binding sites in conformation E1.

PMID- 7729367
TI  - A long lifetime component in the tryptophan fluorescence of some proteins.
AB  - The tryptophan fluorescence of two membrane proteins (outer membrane protein A
      and lactose permease), a 21-residue hydrophobic peptide, three soluble proteins
      (rat serum albumin, ribonuclease T1, and azurin), and N-acetyltryptophanamide
      (NATA) was investigated by time-resolved measurements extended over 65 ns. A long
      lifetime component with a characteristic time of 25 ns and an amplitude below 1%
      was found for outer membrane protein A, lactose permease, the peptide in lipid
      membranes, and azurin in water, but not for rat serum albumin, ribonuclease T1,
      and NATA in water. When outer membrane protein A was dissolved and unfolded in
      guanidinum hydrochloride, the long lifetime component disappeared. Hence, a
      hydrophobic environment seems to be a necessary requirement for the long lifetime
      component to be present. However, NATA dissolved in butanol does not exhibit the
      long lifetime component, while the peptide dissolved in the same solvent under
      conditions which preserve its helical structure does show the long lifetime.
      Thus, a regular secondary structure for the polypeptide chain to which the
      tryptophan residue belongs seems to be a second necessary requirement for the
      long lifetime component to be present. The long lifetime component may therefore
      be seen in the context of protein substates.

PMID- 7729368
TI  - Modelling endplate currents: dependence on quantum secretion probability and
      decay of miniature current.
AB  - Quantification of the time course and amplitude of endplate currents (EPC) was
      made with respect to dispersion of quanta secretion and to changes in the
      exponential decay of miniature endplate currents (tau mepc). The relationship
      between RPC amplitude and tau mepc follows a double-exponential curve with tau1 =
      0.3 ms and tau2 = 6 ms. If the amplitude of fully synchronised EPC is taken as
      100%, then the loss of EPC amplitude is already 42% with "physiological"
      parameters of dispersion (the half-rise and decay constant of distribution of
      secretion probability = 0.5 ms, taumepc = 1 ms). This loss is even more
      substantial if secretion is more dispersed or miniature endplate currents decay
      faster.

PMID- 7729369
TI  - Interaction of chlorpromazine with phospholipid membranes. An EPR study of
      membrane surface potential effects.
AB  - The interaction of chlorpromazine (CPZ) with artificial membranes (egg-yolk
      phosphatidylcholine liposomes) has been studied. Measurements of the surface
      electric potential, which is modified in the presence of the ionized form of the
      drug, were obtained by electron paramagnetic resonance spectroscopy (EPR) using a
      positively charged amphiphilic spin-probe. This probe partitions between the
      aqueous and lipidic phases depending on the surface potential and on the
      structural state of the membrane. The surface potential was measured as a
      function of drug concentration in the range where the spectral line-shapes are
      not affected by the incorporation of the drug. From these experimental results
      and through an appropriate formalism we obtain information on the binding of the
      drug to the lipid bilayer and on the ionization of the drug in the lipidic phase.

PMID- 7729370
TI  - Characterization of a marker for tracheal basal cells.
AB  - An IgM monoclonal antibody (1D9/B3) is characterized, which specifically
      recognizes basal cells of the upper airway epithelium. Although morphological
      features have been used to follow cell lineage and differentiation, an objective
      assessment of differentiation can be enhanced by characterizing the expression of
      specific antigens that form the phenotypic profile of specialized cells. Mice
      were immunized with rabbit tracheal basal cells that had been obtained by pronase
      digestion and purified into a subpopulation of basal cells by flow cytometry. Six
      immunization experiments produced five hybridomas specific to epithelial cells. A
      hybridoma whose supernatant immunocytochemically stained the basal cell
      subpopulation of rabbit tracheal cells was selected. The antibody reacted with
      tracheal basal cells in rabbit, rat, sheep, pig, and human tracheal sections, and
      in cultured monolayers of tracheal epithelial cells of the same species. The
      antibody did not react with the basal cells of other rabbit tissue, including the
      skin, or other rabbit epithelia. Confocal microscopy and exposure of tracheal
      epithelial cells to fluorescent-tagged monoclonal antibody 1D9/B3 prior to
      loading on to flow cytometry showed that the basal cell antibody recognized an
      intracellular epitope. The epitope for the 1D9/B3 antibody was characterized by
      Western blotting. The 1D9/B3 antibody appears to be a distinct and specific
      marker to the airway epithelial basal cell and will be useful in studies of
      airway epithelial differentiation, injury, and regeneration.

PMID- 7729371
TI  - Alteration of pulmonary macrophage intracellular pH following inhalation exposure
      to sulfuric acid/ozone mixtures.
AB  - Recent studies have demonstrated that additive and synergistic effects on rabbit
      pulmonary macrophages (PM phi) function can occur after combined exposures to
      acid aerosols and ozone. This study investigated intracellular pH (pHi)
      homeostasis and H+ extrusion mechanisms of PM phi from rabbits exposed to
      sulfuric acid, ozone, and their mixtures. Animals were exposed for 3 h to 125
      micrograms/m3 sulfuric acid, 0.1, 0.3, 0.6 ppm ozone, or combinations of acid
      with each concentration of ozone, and the pHi was determined by a fluorescent dye
      ratioing technique. Exposure to 125 micrograms/m3 acid reduced pHi and exposure
      to ozone resulted in a concentration-dependent reduction in pHi. Ozone generally
      tended to mitigate the effect of the acid aerosol on pHi. Other groups of rabbits
      were exposed to 50 micrograms/m3 sulfuric acid, 0.6 ppm ozone, or their mixture,
      for 3 h, and PM phi were again harvested. The pHi of PM phi following exposure to
      each of the pollutant atmospheres was not different from control. However, H+
      extrusion with an imposed internal acid load was found to be significantly
      depressed following exposure to either sulfuric acid or ozone alone, while the
      mixture produced a significant interaction.

PMID- 7729372
TI  - Nonspecific bronchial responsiveness assessed in vitro following acute inhalation
      exposure to ozone and ozone/sulfuric acid mixtures.
AB  - Air pollution may play some role in the recent increase in severity and
      prevalence of asthma, but the specific chemical components with the ambient
      pollutant mix that may be responsible have not been delineated. Since ambient
      exposures involve mixtures, it is essential to examine airway responses to
      realistic pollutant mixtures. This study examined the ability of single (3-h)
      inhalation exposures to ozone and to mixtures of ozone plus sulfuric acid to
      induce nonspecific airway hyperresponsiveness in healthy rabbits. Airway
      responsiveness was assessed using an in vitro assay involving administration of
      increasing doses of acetylcholine to bronchial rings obtained from animals
      exposed to 0.1-0.6 ppm ozone or to mixtures of ozone and 50-125 micrograms/m3
      sulfuric acid aerosol; results were compared to those reported previously for
      sulfuric acid alone. Bronchial hyperresponsiveness to ozone was noted following
      exposure at all concentrations, but the combination of pollutants results in
      antagonism. The results support the potential for ozone to induce airway
      hyperresponsiveness in healthy animals and suggest that interaction with sulfuric
      acid may reduce the effectiveness of both pollutants.

PMID- 7729373
TI  - Hyperoxia-induced alterations of rat alveolar lavage composition and properties.
AB  - Although lethal exposures of most animal species to oxygen result in a reduced
      amount of surfactant phospholipids (PL), hyperoxia in rats leads to elevated
      levels of PL on the alveolar surface. Because of this different response, a study
      was made of the amount, composition, surface properties, and subfraction
      distribution (obtained by differential centrifugation) of alveolar lavage
      materials from rats exposed to > 95% oxygen for 64 h. The exposures lead to
      severe lung damage, which includes the appearance of pleural effusion, pulmonary
      edema, and increased protein levels on the alveolar surface. However, the PL
      levels of lavage fluid are increased two- to threefold, and the PL composition is
      altered. In O2-exposed rats, only 39(+/- 1)% of the phospholipid is disaturated
      phosphatidylcholine (DSPC), the major surface active component of surfactant, as
      compared to 46(+/- 1)% DSPC in lavage from control animals. The distribution of
      PL and DSPC in subfractions of lavage materials obtained by differential
      centrifugation is approximately reversed following hyperoxia. In lavage from
      control animals, 36% of the PL is in the heavier, more dense subfractions and 64%
      is in the lighter, less dense subfractions, while 72% is heavier and 28% lighter
      in lavage from O2-exposed animals. Measurements of surface properties with the
      Wilhelmy balance indicate that the ability of the lavage materials to reduce
      surface tension is impaired following hyperoxia. Thus, lethal exposures of rats
      to oxygen lead to increased amounts of surfactant on the alveolar surface, but
      the surface properties of the surfactant are impaired, probably due to reduced
      levels of DSPC, increased amounts of protein, and alterations in its physical
      form.

PMID- 7729374
TI  - Effect of hyperpnea on the cholesterol to disaturated phospholipid ratio in
      alveolar surfactant of rats.
AB  - Hyperpnea induced by swimming rats for 30 min decreased the
      cholesterol/disaturated phospholipid ratio (CHOL/DSP) in the tubular myelin-poor
      fraction (alv-2), but did not affect the tubular myelin-rich fraction (alv-1).
      The phenomenon was further illustrated by the marked inverse relationship between
      CHOL/DSP and DSP. Because such a result could reflect differential release,
      processing, or reuptake within the alveolar compartment, this study further
      explored the mechanism in the rat isolated perfused lung (IPL), using
      radiolabeled CHOL (3H) and DSP (14C). The study also examined whether the
      decrease in CHOL/DSP with swimming was associated with the increase in either
      tidal volume (VT), frequency of breathing (f), or both. It was found that whereas
      a 2.5-fold increase in VT for 15 min in the IPL increased the CHOL/DSP in alv-1
      and decreased it in alv-2, a 3-fold increase in f markedly increased the CHOL/DSP
      in both alveolar subfractions. In apparent contrast, the increases in both VT and
      f markedly depressed the ratio of the sp act of CHOL/DSP, reflecting a large
      decrease in the sp act of CHOL in the alveolar compartment. In view of the acute
      nature of these IPL experiments, it is suggested that the changes reflect the
      differential release of CHOL and DSP. Furthermore, the marked decrease in sp act
      of CHOL must reflect a second source of CHOL supplying the alveolar compartment
      with sterol of low sp act. It is concluded that there is differential handling of
      surfactant CHOL and DSP in the alveolar compartment of the rat and that the
      decrease in CHOL/DSP with swimming is due to an increase in VT.

PMID- 7729375
TI  - Marker proteins in the particulate fraction of third-trimester amniotic fluid.
AB  - The present clinical evaluation of fetal lung maturity relies largely on the
      determination of the amniotic surfactant phospholipids phosphotidylglycerol,
      lecithin, and sphingomyelin, but there are many false negatives as well as false
      positives among diabetics. The use of other components of lung surfactant,
      namely, the hydrophobic surfactant proteins (SPs) has long been suggested as an
      alternative to the classical assay, but tests based on the detection of
      immunoreactive SP-A have not proved superior or supplanted phospholipid ratios as
      an index. This report investigates the proteins in a fraction of third-trimester
      human amniotic fluid (the particulate fraction) enriched in the SP complexes that
      form the surfactant monolayer. The proteins were analyzed by two-dimensional
      polyacrylamide gel electrophoresis and visualized by silver staining and
      immunoblotting. Eight proteins are of particular interest. Three novel proteins
      (termed AFPP-1, AFPP-4, and AFPP-8) and the alpha-fetoprotein/human serum albumin
      complex (AFPP-7) can be detected throughout the 28- to 38-week gestational
      window. The protein that is referred to as AFPP-2 could be identified as SP-A on
      the basis of immunologic cross-reactivity as well as size and charge
      characteristics. The time course of appearance of AFPP-2 was also followed in
      patients with Rh isoimmunization syndrome and was found to be the same as that
      seen for SP-A. The SP-A was detected as at least five major charged isoforms with
      multiple subisoforms of different molecular weight and can be distinguished from
      a related set of proteins (AFPP-5) that appear with a different time course but
      are possible precursors. Two other proteins (AFPP-3, AFPP-6), which are
      detectable inconsistently bear some similarity to others reported previously but
      not extensively characterized. These results define both constant and variable
      proteins of the particulate fraction of the amniotic fluid and indicate that
      certain protein isoforms are changing throughout the third trimester. These data
      enhance the possibility of the utilization of these proteins as markers of lung
      maturity in conditions such as maternal diabetes.

PMID- 7729376
TI  - Response of alveolar macrophage-depleted rats to hyperoxia.
AB  - Recently an alveolar macrophage (AM)-depleted rat model has been characterized
      and it has been demonstrated that AM are required for the endotoxin-induced tumor
      necrosis factor (TNF) release into the alveolar space (J Appl Physiol
      1993;74:2812-2819). The current study investigated the response of AM-depleted
      rats to hyperoxia and evaluated the potential role of AM in the pathogenesis of
      pulmonary O2 toxicity. Rats were insufflated with Hanks' balanced salt solution
      (HBSS), liposome-encapsulated phosphate-buffered saline (PBS-liposomes), or
      liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP-liposomes) and 2
      days later exposed to 100% O2. The effect of hyperoxia was assessed by parameters
      of O2-induced lung injury (e.g., hematocrit value, pleural effusion volume,
      effusion protein to plasma protein ratio, and alveolar lavage fluid protein
      content), TNF release into the alveolar space, and survival. Insufflation of
      Cl2MDP-liposomes, but not HBSS or PBS-liposomes, caused a sustained depletion of
      > 70% AM, which was associated with a slight but significant increase in the
      number of lavageable neutrophils. Twenty percent of AM-depleted rats survived
      longer than 74 h of O2 exposure, while all rats insufflated with HBSS or PBS
      liposomes died within 74 h (p < .05). No significant differences were detected in
      alveolar TNF release or in the extent of O2-induced lung injury.

PMID- 7729377
TI  - Human deposition and clearance of 6-micron particles inhaled with an extremely
      low flow rate.
AB  - In human experimental data, tracheobronchial deposition reaches its maximum for
      particles of about 6 microns inhaled at 0.5 L/s. The purpose of the present study
      was to investigate if tracheobronchial deposition of 6-microns particles could be
      increased, especially in the smaller bronchi, using an extremely slow inhalation
      rate. Six healthy nonsmokers inhaled monodisperse 6-microns (aerodynamic
      diameter) Teflon particles labeled with 111In at 0.04 L/s. Radioactivity in mouth
      and throat, lung, and stomach was measured immediately after inhalation by
      profile scanning and in the lung also after 24, 48, 72, and 96 h. There was a
      substantial clearance between 24 and 72 h; around 20% of the total clearance
      occurred between 24 and 72 h. This is in contrast to earlier studies in which
      only around 1% of 6-microns particles inhaled at 0.5 L/s cleared between 24 and
      72 h. This indicates a markedly higher deposition in the smaller bronchi at 0.04
      L/s than at 0.5 L/s. The total tracheobronchial deposition was 50%, compared to
      about 30% when particles were inhaled at 0.5 L/s. These findings could be
      therapeutic use. They also implicate the possibility of developing a diagnostic
      model that can separate between bronchial reactivity in large and small bronchi.

PMID- 7729378
TI  - Angiotensin-converting enzyme activity is increased in lungs of rats with
      pulmonary hypoplasia and congenital diaphragmatic hernia.
AB  - Lung hypoplasia (LH) and pulmonary hypertension are responsible for the high
      mortality rate in congenital diaphragmatic hernia (CDH) patients. Angiotensin
      converting enzyme (ACE) plays a role in the regulation of pulmonary vascular
      resistance in the postnatal period and might be involved in the development of
      pulmonary hypertension of the newborn. A study was made of the development of ACE
      activity spectrophotometrically in a rat model of LH and CDH. It was previously
      shown that the lungs in this model are hypoplastic and the muscularization of the
      pulmonary vascular bed is increased. CDH was induced in fetal rats by oral
      administration of 115 mg/kg Nitrofen to the mother on day 10.5 of pregnancy.
      Fetuses were delivered by hysterotomy on days 19, 20, 21, and 22. Nitrofen
      exposed rats showed significantly lower lung weights and not statistically
      significant lower total ACE activities than in controls. ACE activity expressed
      per milligram lung wet weight and per milligram protein was significantly
      increased compared to controls. ACE converts angiotensin I to the vasoconstrictor
      angiotensin II, and it inactivates the vasodilator bradykinin. Increased ACE
      activity may therefore contribute to pulmonary hypertension. Whether ACE and
      angiotensin II levels are increased in human newborns with a diaphragmatic defect
      and whether they contribute to the development of persistent pulmonary
      hypertension has not been studied up till now.

PMID- 7729379
TI  - Phagolysosomal morphology and dissolution of cobalt oxide particles by human and
      rabbit alveolar macrophages.
AB  - The effect of phagolysosomal size on dissolution of cobalt oxide particles was
      evaluated in two different macrophage systems: alveolar macrophages (AM) of human
      smokers with phagolysosomes enlarged by ingested cigarette smoke products, and
      rabbit AM incubated in vitro with sucrose, which causes swelling of the
      phagolysosomes by osmosis. Human AM from smokers and nonsmokers were studied in
      vitro. There was no significant difference in particle dissolution between AM
      obtained from smokers and nonsmokers, although there was a clear difference in
      the morphological appearance of AM, including significantly larger phagolysosomes
      in smokers. Rabbit AM were incubated for 24 or 72 h with or without 80 mM sucrose
      in the medium. The sucrose-treated cells had 3-4 times larger phagolysosomes than
      untreated cells, with no major change in phagolysosomal pH. The increased size of
      the phagolysosomes did not affect the ability of the AM to dissolve cobalt oxide
      particles. Furthermore, rabbit AM showed the same ability as human AM to dissolve
      the cobalt oxide particles, in spite of the fact that they had markedly smaller
      phagolysosomes. Another difference between human and rabbit AM was that
      phagolysosomes in human AMs increased in size with time in culture, while rabbit
      AM phagolysosomes decreased in size.

PMID- 7729380
TI  - Maintenance of differentiated phenotype by mouse type 2 pneumocytes in serum-free
      primary culture.
AB  - An improved method has been developed for separation of an enriched population of
      mouse type 2 pneumocytes, based on differential adherence and size fractionation
      of cells dissociated with trypsin. These cells were successfully maintained in
      primary culture in serum-free medium MCDB 201 supplemented with albumin,
      transferrin, and lipids. Whereas type 2 pneumocytes in serum-supplemented culture
      undergo phenotypic transformation into adherent flattened cells that resemble
      type 1 pneumocytes, this did not occur in serum-free culture. Both the morphology
      of the type 2 pneumocytes and their expression of surfactant protein A were
      maintained for at least 6 days in vitro. However, rapid loss of differentiated
      characteristics was induced by exposure of the cells to normal mouse serum. This
      was accompanied by a striking decrease in spontaneous DNA synthesis as assessed
      by incorporation of tritiated thymidine. When cultured in serum-free medium, the
      behavior of the type 2 pneumocytes on various extracellular matrix components was
      different from that reported for serum-supplemented culture. Serum-free culture
      of type 2 pneumocytes may offer significant advantages for evaluation of the
      secretory activities of these cells in vitro.

PMID- 7729381
TI  - Effects of low-dose hydrogen peroxide in the isolated perfused rat lung.
AB  - Isolated perfused rat lungs (IPRL) were used to determine if treatment with
      hydrogen peroxide would result in measurable changes in exhaled ethane during the
      early stages of capillary leak. Pulmonary capillary filtration coefficient,
      pulmonary vascular resistance, and dynamic pulmonary compliance were measured at
      two time points in an IPRL. Additionally, exhaled ethane was determined before
      and after the addition of 0.25 mM H2O2 to the perfusate in a second group of
      lungs. Lung wet/dry weight ratios were measured at the termination of the
      experiments. The ethane in the exhaled alveolar gas from IPRLs ventilated with
      5%CO2/20%O2/balance N2 was quantitated using gas chromatography before and after
      the addition of 0.25 mM H2O2 to Krebs Ringer's 5% albumin perfusate. H2O2 (0.25
      mM) caused a small but significant increase in capillary filtration coefficient
      from 0.0122 (+/- 0.0008) to 0.0173 (+/- 0.0013) mL/min/cm H2O/g dry lung weight
      (p < .05). Wet/dry lung weight ratios were increased in the H2O2-treated lungs
      (6.0654 +/- 0.1024 versus 5.4149 +/- 0.1143; p < .05). Exhaled ethane did not
      increase over the period of time hydrogen peroxide was present in the perfusate.
      In other experiments in closed-chested rats, 0.25 mM peroxide did not cause
      increased exhaled ethane, whereas 1 mM H2O2 did. This latter increase in ethane
      was not noted in similarly perfused open-chested rats. These data indicate that
      small amounts of H2O2 may increase pulmonary capillary permeability without
      affecting exhaled ethane measurements.

PMID- 7729382
TI  - Adverse effects of the indoor environment on respiratory health in primary school
      children.
AB  - Exposure to various factors from the indoor environment on respiratory health of
      470 Dutch primary school children was studied. We investigated which of the
      factors, such as home dampness, passive smoking, unvented kitchen geysers, or
      pets, affected children's respiratory health the most, and whether airway
      sensitivity to these indoors exposures differed between boys and girls.
      Information on respiratory morbidity and characteristics of the housing was
      obtained by a written questionnaire, completed by the parents of the children.
      Lung function of the children was measured at school, by forced oscillation
      technique (FOT) and spirometry. In boys, all investigated lung function
      parameters were significantly affected by exposure to passive smoking during the
      child's entire life. Although mostly nonsignificant, all of the reported asthma
      like symptoms were related especially to maternal smoking, with a trend of a dose
      response relationship. Furthermore, damp stains (P < 0.05) and mold growth (ns)
      were associated with chronic cough and with small but significant impairments in
      part of the lung function parameters. No consistent patterns were observed with
      unvented kitchen geysers and pets. Although passive smoking (cumulative dose) in
      girls was also associated with lung function impairments, the effects were
      smaller than those in boys and not all significant. Associations between the
      asthma-like symptoms and the dose of maternal and paternal smoking also were less
      consistent. Furthermore, no associations were found with the dampness indicators
      and with pets, but unvented kitchen geysers were significantly related to
      impairments in some of the impedance indices. This study shows detrimental
      effects of several indoor factors on the prevalence of chronic respiratory
      symptoms and lung function in children, which are most pronounced for passive
      smoking, and somewhat less pronounced for dampness and the presence of unvented
      kitchen geysers. Airway sensitivity to these exposures appeared to be higher in
      boys than in girls.

PMID- 7729383
TI  - Endemic fluorosis in San Luis Potosi, Mexico. I. Identification of risk factors
      associated with human exposure to fluoride.
AB  - In order to identify risk factors associated with human exposure to fluoride in
      San Luis Potosi (SLP), Mexico, a biochemical and epidemiological study was
      carried out in 1992. Results from the analysis of fluoride sources showed that
      61% of tap water samples had fluoride levels above the optimal level of 0.7-1.2
      ppm. The levels were higher after boiling. In bottled water, fluoride levels
      ranged from 0.33 to 6.97 ppm. These sources are important since in SLP 82% of the
      children drink tap water, 31% also drink bottled water, 92% prepare their food
      with tap water, 44% boiled all the drinking water, and 91% used infant formula
      reconstituted with boiled water. The prevalence and severity of dental fluorosis
      in children (11-13 years old) increased as the concentration of water fluoride
      increased. At levels of fluoride in water lower than 0.7 ppm a prevalence of 69%
      was found for total dental fluorosis, whereas at levels of fluoride in water
      higher than 2.0 ppm a prevalence of 98% was found. In the same children, fluoride
      levels in urine were quantified. The levels increased as the concentration of
      water fluoride increased. Regressional analysis showed an increment of 0.54 ppm
      (P < 0.0001) of fluoride in urine for each ppm of fluoride in water. Fluoride
      urinary levels were higher in samples collected during the afternoon (1800) when
      compared with sample collected during the morning (1100). Taking together all
      these results, three risk factors for human exposure to fluoride in SLP can be
      identified: ambient temperature, boiled water, and food preparation with boiled
      water. These factors explain the prevalence of dental fluorosis in SLP.

PMID- 7729384
TI  - Lifetime excess risk of death from lung cancer for a U.S. female never-smoker
      exposed to environmental tobacco smoke.
AB  - There is considerable evidence that exposure to environmental tobacco smoke (ETS)
      in the home increases the risk of lung cancer in female nonsmokers. A risk
      assessment was conducted to estimate the lifetime excess risk of death from lung
      cancer for a U.S. female never-smoker exposed to ETS in different settings.
      Relative risks for social and occupational exposures were calculated using a
      relative risk of 1.185 for home exposure (calculated from a recent metaanalysis
      of U.S. studies) and the results of studies that compare home exposure to
      exposures outside the home. Each relative risk was used to convert lung cancer
      mortality rates for U.S. female never-smokers into a lifetime excess risk, using
      a formula which accounts for competing causes of death. The excess risk for home
      exposure is 6.5 x 10(-4) (6.5 excess deaths per 10,000 never-smokers). For social
      and overall workplace exposures, excess risks range from 1.4 x 10(-4) to 3.6 x
      10(-4) and from 9.8 x 10(-6) to 1.4 x 10(-4), respectively. Exposures in offices,
      restaurants, and bars result in excess risks that range from 1.5 x 10(-4) to 9.0
      x 10(-4). All of these estimates are greater than an acceptable risk level of 10(
      6). The results of this analysis support efforts to restrict or eliminate smoking
      in public places and work sites.

PMID- 7729385
TI  - Estimation of variation among individuals of biological half-time of cadmium
      calculated from accumulation data.
AB  - For heavy metals, many experimental studies using animals have revealed short
      biological half-times (BHTs) to be 1 year or less by administration of heavy
      metals. Tsuchiya and Sugita, however, devised an original method and first
      reported the possibility of a long BHT for cadmium (Cd) calculated from Cd
      accumulation in postmortem human organs and tissues by age using a nonlinear
      regression analysis employing a differential equation. According to their
      reports, the estimated values of Cd BHT were 12.1-22.7 years in the kidney. The
      estimated Cd BHTs are point estimators. The point estimator of Cd BHT has been
      used indiscriminately to derive safety levels for Cd in the air of work
      environments or foodstuffs in the general population without taking into
      consideration individual variation of Cd BHT. In the present study, the estimated
      variation among individuals of Cd BHT ranges from a few years to at least 100
      years in the kidney. It is concluded that the estimated average BHT according to
      mathematical calculation should not be used indiscriminately to derive the safety
      level of cadmium exposure.

PMID- 7729386
TI  - Induction of preneoplastic lesions by sodium arsenite in human fetal respiratory
      epithelia in organ culture.
AB  - The effects of sodium arsenite (As) and N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG) on epithelia of human fetal trachea and bronchiolar epithelia of human
      fetal lung were studied by using organ-cultured explants. In epithelium of human
      fetal trachea, 34 microM MNNG induced hyperplasia, metaplasia, and dysplasia; 1
      microM As induced hyperplasia; and 3-9 microM As induced hyperplasia and cellular
      atypia. In glandular epithelium of human fetal trachea, 34 microM MNNG induced
      hyperplasia and metaplasia; 1 microM As did not induce obvious changes; and 3-9
      microM As induced hyperplasia and epidermoid metaplasia with nuclear atypia. In
      bronchiolar epithelium of human fetal lung, the induction of dysplasia was
      observed for 1 microM As. Arsenic-induced preneoplastic lesions support the
      conclusion of epidemiological studies that arsenic is carcinogenic to human lung.

PMID- 7729387
TI  - Lead levels in the household environment of children in three high-risk
      communities in California.
AB  - To assess environmental lead contamination in the household environment of
      children in high-risk areas of California, three urban locations were surveyed by
      the California Department of Health Services. Plant, soil, and dust lead levels
      were measured and a questionnaire was administered. This survey estimates that 3
      million homes in California (27%) may have exterior paint lead levels > or = 5000
      ppm, and 1.3 million homes (12%) may have interior paint lead levels > or = 5000
      ppm. The highest concentrations of lead in paint were found on exterior surfaces
      and, for homes built between 1920 and 1959, on trim. Age of housing was the best
      predictor of lead in soil and dust; homes built before 1920 were 10 times more
      likely to have soil lead levels > or = 500 ppm compared to post-1950 homes. Most
      of the variability in dust lead levels could not be explained by factors measured
      in this survey. Sources of lead in the home were more highly correlated with lead
      dust concentration levels than they were with lead dust loading levels.
      Households with members reporting a lead job were twice as likely to have high
      dust lead levels compared to households with no one reporting a lead job. The
      significant differences in dust lead concentration levels between communities
      were not reflected in differences in dust lead loading levels. Measuring dust
      lead loading levels does not appear to be a meaningful sampling method for risk
      assessment in the context of prioritizing abatement.

PMID- 7729388
TI  - Environmental tobacco smoke: nicotine and cotinine concentration in semen.
AB  - Forty-three nonsmokers attending an infertility clinic reported their degree of
      passive exposure to environmental tobacco smoke (ETS) and provided samples of
      blood and seminal plasma. Levels of nicotine and cotinine in biological fluid
      were evaluated by a radioimmunoassay. The data indicate that exposure to ETS
      results in measurable nicotine and cotinine levels in seminal plasma. Seminal
      plasma cotinine concentration also shows a significant positive correlation with
      degree of reported exposure.

PMID- 7729389
TI  - Festschrift for Professor W. T. Singleton.

PMID- 7729390
TI  - Compensation for occupational injuries and diseases: its effect upon prevention
      at the workplace.
AB  - In Switzerland, as in many other industrialized countries, the nature and extent
      of prevention at the workplace is determined, at least partially, by known cases
      of compensated occupational injuries and diseases. At both the national and
      international levels (ILO conventions), injuries and diseases that fit
      appropriate lists and definitions are eligible for compensation. It has been
      found, based upon an investigation of a representative sample (965 subjects) of
      the working population in the French-speaking region of Switzerland, that this
      restrictive view does not take into account the fact that a large proportion of
      injuries and diseases are claimed by the victims to be caused by their job. These
      injuries and diseases, responsible for at least one month's absence from work,
      are not considered to be eligible for compensation but must be covered by the
      patient's own insurance. Moreover, the survey showed that workers considered the
      ill effects on health and safety to be a consequence less of the physical working
      environment than of the work organization, and that this category of risks was
      not recognized. Thus, in addition to the reduction of hazards by the application
      of industrial hygiene, an informed improvement of the workplace and the work
      organization was required. Consequently, laws and regulations on occupational
      injuries and diseases should be changed in order to emphasize the role of more
      appropriate preventive tools, which includes ergonomics.

PMID- 7729391
TI  - Occupational slips and falls: more than a trivial problem.
AB  - The significance of occupational falls is established through analysis of
      workers' compensation data of a major insurance company. The data covered 11% of
      the American privately insured workforce and exposure estimates were based on
      Bureau of Labor Statistics demographics. The number of incidents and the relative
      cost of falls were examined by age, gender, industry, climate and geographic
      region and empirical data are presented. These data establish the enormous cost
      of falls measured in terms of individual pain and suffering and in losses to
      industrial organizations.

PMID- 7729392
TI  - Wrist postures while keyboarding: effects of a negative slope keyboard system and
      full motion forearm supports.
AB  - Video-motion analysis was used to analyse hand/wrist posture for subjects typing
      at a 101-key QWERTY keyboard on a 68 cm high worksurface. Three conditions were
      tested: subjects typed at the keyboard without arm support, subjects typed with
      adjustable full motion forearm supports, and subjects typed with an adjustable
      negative slope keyboard support system. The average declination of the negative
      slope keyboard support chosen by subjects was 12 degrees below horizontal, which
      flattened the angle of the key tops. Ulnar deviation was comparable in all
      conditions and averaged 13 degrees for the right hand and 15 degrees for the left
      hand. Full motion forearm supports did not significantly affect any postural
      measures. Dorsal wrist extension averaged 13 degrees when typing with or without
      the full motion forearm supports, but this was reduced to an average -1 degree
      with the use of the negative slope keyboard support system. Subjects chose to sit
      at a distance of 79 cm from the computer screen when using the negative slope
      keyboard system compared with 69 cm without this.

PMID- 7729393
TI  - A personal perspective on aging and productivity, with particular reference to
      physically demanding work.

PMID- 7729394
TI  - An exploratory study of arm-reach reaction time and eye-hand coordination.
AB  - The study examined the time taken to reach and touch keys positioned both within
      and just outside the traditional reach envelope, as well as within and just
      outside the region of easy visibility, defined as being within a 30 degrees cone
      centered on the line of sight. Movements were required from a start key
      positioned in front of the subject to a response key positioned at one of 140
      positions, defined by seven heights (from 360 to 1080 mm above the seat reference
      point (SRP), five angles (in vertical planes positioned from 30 degrees across
      the body to 90 degrees ipsilaterally) and four radii (from 200 mm closer to the
      body than the normal reach boundary to 100 mm further away than the normal reach
      boundary). The time taken was divided into detection time (the time from
      illumination of response signal to release of start key), and movement time (the
      time from release of start key to contact with response key). Results suggested
      that the visual cone should be extended downwards, as detection time increased
      rapidly to keys positioned outside the visual cone upwards, but not in the
      downwards direction. In general, responses to keys positioned anywhere that was
      both within the reach envelope and also within the visual cone took approximately
      the same time, from 371 to 420 ms. Movement time increased with distance moved,
      but disproportionately so, up to 595 ms, when movement was required to positions
      that were at one or more of the extremes of height, angle or radius.

PMID- 7729395
TI  - The psychophysical lifting capacities of Chinese subjects.
AB  - The psychophysical lifting capacity (MAWL) of twelve subjects was determined in
      this study. The subjects were all young Chinese males who performed lifting tasks
      in three lifting ranges (floor to knuckle, floor to shoulder, and knuckle to
      shoulder) and four lifting frequencies (one-time maximum, 1 lift/min, 4
      lifts/min, and 6 lifts/min). The oxygen uptake (1/min) and heart rate (beats/min)
      were recorded while subjects were lifting. Upon completion of each lifting task,
      the subjects were required to rate their perceived exertion levels. The
      statistical analyses results indicated the following. Chinese subjects have
      smaller body size and MAWLs compared with past studies using the US population.
      The MAWLs decreased with an increase in lifting frequencies. The decrements of
      MAWL due to lifting frequencies were in agreement with the results of past
      studies. However, there were larger decreases due to lifting ranges. The MAWLs of
      the floor to knuckle height lift were the largest, followed by the MAWLs of the
      floor to shoulder height lift, and the MAWLs of the knuckle to shoulder height
      lift. The measured physiological responses were considered similar to those
      obtained in past studies. Subjects' perceived stress levels increased with the
      lifting frequency and the upper extremities received the most stress for the
      total range of lifting tasks. The comparisons of the Chinese MAWLs with the NIOSH
      lifting guidelines for limits (AL and MPL) indicated that the vertical
      discounting factor in the guidelines should be modified before the NIOSH limits
      can be applied to non-Western populations.

PMID- 7729396
TI  - A study of hand grip pressure distribution and EMG of finger flexor muscles under
      dynamic loads.
AB  - A matrix of miniature and flexible pressure sensors is proposed to measure the
      grip pressure distribution (GPD) at the hand-handle interface of a vibrating
      handle. The GPD was acquired under static and dynamic loads for various levels of
      grip forces and magnitudes of vibration at different discrete frequencies in the
      20-1000 Hz range. The EMG of finger flexor muscles was acquired using the silver
      silver chloride surface electrodes under different static and dynamic loads. The
      measured data was analysed to study the influence of grip force, and magnitude
      and frequency characteristics of handle vibration on: (i) the local concentration
      of forces at the hand-handle interface; and (ii) the electrical activity of the
      finger flexor muscles. The results of the study revealed high interface pressure
      near the tips of index and middle fingers, and base of the thumb under static
      grip conditions. This concentration of high pressure shifted towards the middle
      of the fingers under dynamic loads, irrespective of the grip force, excitation
      frequency, and acceleration levels. The electrical activity of the finger flexor
      muscles increased considerably with the grip force under static as well as
      dynamic loads. The electrical activity under dynamic loads was observed to be 1.5
      6.0 times higher than that under the static loads.

PMID- 7729397
TI  - Overhead work and shoulder-neck pain in orchard farmers harvesting pears and
      apples.
AB  - The effects of overhead work were studied by comparing orchard farmers'
      musculoskeletal symptoms while bagging pears with those same symptoms while
      bagging apples. The subjects were 52 Japanese female farmers, who were examined
      twice an evening in late June for bagging pears, and during another evening of
      late July for bagging apples, when each task had been almost finished. They were
      questioned about musculoskeletal complaints of stiffness and pain during each
      job, and examined for muscle tenderness and pain from joint movement. Arm
      elevation angles during the work were measured for each type of bagging. The
      prevalence of stiffness and pain in the neck and shoulder, muscle tenderness in
      the shoulder regions, and pain in neck motion were found to be significantly
      higher when bagging pears than apples. Musculoskeletal symptoms of parts other
      than the neck and shoulder did not differ between the two types of bagging. The
      working posture of elevating the arm more than 90 degrees was assumed to account
      for 75% of the time bagging pears, against 40% for bagging apples. Overhead work
      requiring arm elevation and head extension was considered to be closely related
      with shoulder-neck disorders among farmers.

PMID- 7729398
TI  - An evaluation of respiratory protective devices used in children's evacuation.
AB  - This study evaluated respiratory protective devices (RPDs) used in children's
      evacuation. The RPDs evaluated were either a protective jacket or a protective
      mask. One hundred and sixty children participated. Half were evacuated from home
      with the help of their parents, whereas the other half were evacuated from day
      care centres with the help of staff. In all, 65% of the children were evacuated
      wearing their RPDs. No significant differences were found between the two
      environments, but significantly more children (75%) kept the mask on than the
      jacket (55%). However, many more cases of improper fit after dressing were
      observed with the mask than with the jacket. Speech communication was observed to
      be reduced for 58% of the children, wearing the mask, and slightly more for those
      wearing the jacket. Children who did not evacuate with the RPDs on were observed
      to be more anxious and adults' attitudes towards them were rated as more neutral,
      whereas children who successfully evacuated were less anxious and adults'
      attitudes towards them were rated both as more positive and as more negative.

PMID- 7729399
TI  - Visually-controlled leg movements embedded in a walking task.
AB  - Accurate control of alternating leg movements in walking was considered as a
      visually controlled target aiming task. Nine subjects aimed alternate feet at
      targets along a walkway, using nine combinations of amplitude and target width
      giving index of difficulty values between 2.59 and 6.16. Movement time was
      compared to the same subjects performing reciprocal tapping tasks with arm and
      leg. Alternating target aiming tasks were the most rapid of all tasks studied.
      Explanations of this effect in terms of learning and elimination of direction
      changes were consistent with the data from all conditions. Visual control can be
      expected in normal walking only for target sizes smaller than about 300 mm, i.e.,
      under unusual accuracy requirements.

PMID- 7729400
TI  - An ergonomic evaluation of dexterity and tactility with increase in
      examination/surgical glove thickness.
AB  - Latex gloves of five different thicknesses (0.21 mm, 0.51 mm, 0.65 mm, 0.76 mm,
      and 0.83 mm) were manufactured in-house and tested for dexterity and tactility;
      dexterity and tactility measures with the bare hand were used as control values.
      Fifteen adult males (mean age = 22.8 years, mean stature = 179 cm, mean body
      weight = 75.4 kg, mean palm width = 9.9 cm, mean palm depth = 10.9 cm, and mean
      middle finger length = 9 cm) and five adult females (mean age = 21.2 years, mean
      stature = 168 cm, mean body weight = 53.6 kg, mean palm width = 8 cm, mean palm
      depth = 8 cm, and mean middle finger length = 8.3 cm) voluntarily participated.
      The gloves also were tested for punctures resulting from impact forces
      encountered during routine hand movements. The results indicated that the latex
      glove with 0.83 mm thickness successfully resisted routine impact forces and at
      the same time provided dexterity and tactility comparable to the bare hand.
      Thinner gloves failed the impact test and punctured. This indicates that it is
      possible to greatly reduce the incidence of exposure to contaminated body fluids
      through accidental needlesticks without compromising the preferred hand's
      capabilities.

PMID- 7729401
TI  - Energy expenditure and clearing snow: a comparison of shovel and snow pusher.
AB  - In order to assess the energy demands of manual clearing of snow, nine men did
      snow clearing work for 15 min with a shovel and a snow pusher. The depth of the
      snowcover was 400-600 mm representing a very heavy snowfall. Heart rate (HR),
      oxygen consumption (VO2), pulmonary ventilation (VE), respiratory exchange ratio
      (R), and rating of perceived exertion (RPE) were determined during the work
      tasks. HR, VE, R, and RPE were not significantly different between the shovel and
      snow pusher. HR averaged (+/- SD) 141 +/- 20 b min-1 with the shovel, and 142 +/-
      19 beats.min-1 with the snow pusher. VO2 was 2.1 +/- 0.41.min-1 (63 +/- 12%VO2
      max) in shovelling and 2.6 +/- 0.51.min-1 (75 +/- 14%VO2max) in snow pushing (p <
      0.001). In conclusion manual clearing of snow in conditions representing heavy
      snowfalls was found to be strenuous physical work, not suitable for persons with
      cardiac risk factors, but which may serve as a mode of physical training in
      healthy adults.

PMID- 7729402
TI  - The influence of VDT work on musculoskeletal disorders.
AB  - Relationships between visual display terminal (VDT) use and musculoskeletal
      problems were examined in a group of 353 office workers, using data from medical
      and workplace investigations as well as questionnaires. There were no general
      differences between VDT and non-VDT users as to the occurrence of muscle
      problems. Combinations of specific VDT work situations such as data entry work or
      work with a VDT for more than 20 h/week and the presence of some other factors
      were, however, associated with excess risks of certain muscle problems. The
      extraneous factors involved in the definitions of such risk groups were: use of
      bifocal or progressive glasses at a VDT; stomach-related stress reactions;
      limited rest break opportunity; repetitive movements; non-use of lower arm
      support; and possibly the vertical position of the keyboard; and presence of
      specular glare.

PMID- 7729403
TI  - Musculoskeletal disorders among visual display terminal workers: individual,
      ergonomic, and work organizational factors.
AB  - A number of individual, ergonomic, and organizational factors of presumed
      importance for the occurrence of musculoskeletal disorders were investigated in a
      group of 260 visual display terminal (VDT) workers. The cross-sectional study
      utilized medical and workplace investigations as well as questionnaires. The
      results were subjected to a multivariate analysis in order to find the major
      factors associated with various upper-body muscular problems. Several such
      factors were identified for each investigated type of musculoskeletal problem.
      Some were related to the individual: age, gender, woman with children at home,
      use of spectacles, smoking, stomach-related stress reactions, and negative
      affectivity. Organizational variables of importance were opportunities for
      flexible rest breaks, extreme peer contacts, task flexibility, and overtime.
      Identified ergonomic variables were static work posture, hand position, use of
      lower arm support, repeated work movements, and keyboard or VDT vertical
      position.

PMID- 7729404
TI  - A national cross-sectional study in the Danish wood and furniture industry on
      working postures and manual materials handling.
AB  - Musculoskeletal disorders constitute a major problem in the wood and furniture
      industry and identification of risk factors is needed urgently. Therefore,
      exposures to different work tasks and variation in the job were recorded based on
      an observation survey in combination with an interview among 281 employees
      working in wood working and painting departments. A questionnaire survey
      confirmed high frequencies of symptoms from the musculoskeletal system: The one
      year prevalence of symptoms from the low back was 42% and symptoms from the
      neck/shoulder was 40%. The exposure was evaluated based on: (1) classification of
      work tasks, (2) work cycle time, (3) manual materials handling, (4) working
      postures, and (5) variation in the job. Among the employees 47% performed feeding
      or clearing of machines, 35% performed wood working or painting materials, and
      18% performed various other operations. Among the employees 20% had no variation
      in their job while 44% had little variation. Manual materials handling of 375
      different burdens was observed, which most often occurred during feeding or
      clearing of machines. The weight of burdens lifted was 0.5-87.0 kg, where 2% had
      a weight of more than 50 kg. Among the lifting conditions 30% were evaluated as
      implying a risk of injury. An additional risk factor was the high total tonnage
      lifted per day, which was estimated to range from 132 kg to 58,800 kg. Working
      postures implied a risk of injury due to prolonged forward and lateral flexions
      of the neck, which was seen most frequently during wood working or painting
      materials. These data substantiate the finding that work tasks mainly during
      feeding or clearing of machines imply a risk of injury to the low back and a risk
      of injury to the neck and shoulder area mainly during wood working or painting
      materials. Optimal strategies for job redesign may be worked out by using these
      data in order to prevent occupational musculoskeletal disorders.

PMID- 7729405
TI  - Voluntary redistribution of muscle activity in human shoulder muscles.
AB  - Four shoulder muscles (the supraspinatus, the infraspinatus, the anterior and
      middle portion of the deltoid, and the descending part of the trapezius) were
      examined with electromyography in abducted arm positions. By using feedback
      techniques, we found that the subjects could reduce the EMG activity voluntarily
      by 22-47% in the trapezius muscle while keeping different static postures. This
      was not true for any other muscle investigated. When the trapezius activity was
      reduced there was a tendency towards an increase of EMG activity in some other
      shoulder muscles, particularly the infraspinatus. The findings may be related to
      relaxation from an initial overstabilization of the shoulder, or redistribution
      of load among synergists. It is suggested that the possibility of reducing
      trapezius activity may be of ergonomic significance. It is also noted that EMG
      trapezius activity may not serve as a universal descriptor of total muscular load
      in the shoulder.

PMID- 7729406
TI  - A comparison of tactile, auditory, and visual feedback in a pointing task using a
      mouse-type device.
AB  - A mouse was modified to add tactile feedback via a solenoid-driven pin projecting
      through a hole in the left mouse button. An experiment is described using a
      target selection task under five different sensory feedback conditions ('normal',
      auditory, colour, tactile, and combined). No differences were found in overall
      response times, error rates, or bandwidths; however, significant differences were
      found in the final positioning times (from the cursor entering the target to
      selecting the target). For the latter, tactile feedback was the quickest, normal
      feedback was the slowest. An examination of the spatial distributions in
      responses showed a peaked, narrow distribution for the normal condition, and a
      flat, wide distribution for the tactile (and combined) conditions. It is argued
      that tactile feedback allows subjects to use a wider area of the target and to
      select targets more quickly once the cursor is inside the target. Design
      considerations for human-computer interfaces are discussed.

PMID- 7729407
TI  - Evolutionary link between glycogen phosphorylase and a DNA modifying enzyme.
AB  - We report here an unexpected similarity in three-dimensional structure between
      glucosyltransferases involved in very different biochemical pathways, with
      interesting evolutionary and functional implications. One is the DNA modifying
      enzyme beta-glucosyltransferase from bacteriophage T4, alias UDP-glucose:5
      hydroxymethyl-cytosine beta-glucosyltransferase. The other is the metabolic
      enzyme glycogen phosphorylase, alias 1.4-alpha-D-glucan:orthophosphate alpha
      glucosyltransferase. Structural alignment revealed that the entire structure of
      beta-glucosyltransferase is topographically equivalent to the catalytic core of
      the much larger glycogen phosphorylase. The match includes two domains in similar
      relative orientation and connecting helices, with a positional root-mean-square
      deviation of only 3.4 A for 256 C alpha atoms. An interdomain rotation seen in
      the R- to T-state transition of glycogen phosphorylase is similar to that
      observed in beta-glucosyltransferase on substrate binding. Although not a single
      functional residue is identical, there are striking similarities in the spatial
      arrangement and in the chemical nature of the substrates. The functional
      analogies are (beta-glucosyltransferase-glycogen phosphorylase): ribose ring of
      UDP-pyridoxal ring of pyridoxal phosphate co-enzyme; phosphates of UDP-phosphate
      of co-enzyme and reactive orthophosphate; glucose unit transferred to DNA
      terminal glucose unit extracted from glycogen. We anticipate the discovery of
      additional structurally conserved members of the emerging glucosyltransferase
      superfamily derived from a common ancient evolutionary ancestor of the two
      enzymes.

PMID- 7729408
TI  - Drosophila UDP-glucose:glycoprotein glucosyltransferase: sequence and
      characterization of an enzyme that distinguishes between denatured and native
      proteins.
AB  - A Drosophila UDP-glucose:glycoprotein glucosyltransferase was isolated, cloned
      and characterized. Its 1548 amino acid sequence begins with a signal peptide,
      lacks any putative transmembrane domains and terminates in a potential
      endoplasmic reticulum retrieval signal, HGEL. The soluble, 170 kDa glycoprotein
      occurs throughout Drosophila embryos, in microsomes of highly secretory
      Drosophila Kc cells and in small amounts in cell culture media. The isolated
      enzyme transfers [14C]glucose from UDP-[14C]Glc to several purified extracellular
      matrix glycoproteins (laminin, peroxidasin and glutactin) made by these cells,
      and to bovine thyroglobulin. These proteins must be denatured to accept glucose,
      which is bound at endoglycosidase H-sensitive sites. The unusual ability to
      discriminate between malfolded and native glycoproteins is shared by the rat
      liver homologue, previously described by A.J. Parodi and coworkers. The amino
      acid sequence presented differs from most glycosyltransferases. There is weak,
      though significant, similarity with a few bacterial lipopolysaccharide
      glycotransferases and a yeast protein Kre5p. In contrast, the 56-68% amino acid
      identities with partial sequences from genome projects of Caenorhabditis elegans,
      rice and Arabidopsis suggest widespread homologues of the enzyme. This
      glucosyltransferase fits previously proposed hypotheses for an endoplasmic
      reticular sensor of the state of folding of newly made glycoproteins.

PMID- 7729409
TI  - Somatodendritic localization and hyperphosphorylation of tau protein in
      transgenic mice expressing the longest human brain tau isoform.
AB  - Microtubule-associated protein tau is the major constituent of the paired helical
      filament, the main fibrous component of the neurofibrillary lesions of
      Alzheimer's disease. Tau is an axonal phosphoprotein in normal adult brain. In
      Alzheimer's disease brain tau is hyperphosphorylated and is found not only in
      axons, but also in cell bodies and dendrites of affected nerve cells. We report
      the production and analysis of transgenic mice that express the longest human
      brain tau isoform under the control of the human Thy-1 promoter. As in
      Alzheimer's disease, transgenic human tau protein was present in nerve cell
      bodies, axons and dendrites; moreover, it was phosphorylated at sites that are
      hyperphosphorylated in paired helical filaments. We conclude that transgenic
      human tau protein showed pre-tangle changes similar to those that precede the
      full neurofibrillary pathology in Alzheimer's disease.

PMID- 7729410
TI  - A focal adhesion factor directly linking intracellularly motile Listeria
      monocytogenes and Listeria ivanovii to the actin-based cytoskeleton of mammalian
      cells.
AB  - The surface-bound ActA polypeptide of the intracellular bacterial pathogen
      Listeria monocytogenes is the sole listerial factor needed for recruitment of
      host actin filaments by intracellularly motile bacteria. Here we report that
      following Listeria infection the host vasodilator-stimulated phosphoprotein
      (VASP), a microfilament- and focal adhesion-associated substrate of both the cAMP
      and cGMP-dependent protein kinases, accumulates on the surface of
      intracytoplasmic bacteria prior to the detection of F-actin 'clouds'. VASP
      remains associated with the surface of highly motile bacteria, where it is
      polarly located, juxtaposed between one extremity of the bacterial surface and
      the front of the actin comet tail. Since actin filament polymerization occurs
      only at the very front of the tail, VASP exhibits properties of a host protein
      required to promote actin polymerization. Purified VASP binds directly to the
      ActA polypeptide in vitro. A ligand-overlay blot using purified radiolabelled
      VASP enabled us to identify the ActA homologue of the related intracellular
      motile pathogen, Listeria ivanovii, as a protein with a molecular mass of
      approximately 150 kDa. VASP also associates with actin filaments recruited by
      another intracellularly motile bacterial pathogen, Shigella flexneri. Hence, by
      the simple expedient of expressing surface-bound attractor molecules, bacterial
      pathogens effectively harness cytoskeletal components to achieve intracellular
      movement.

PMID- 7729411
TI  - The absence of Emp24p, a component of ER-derived COPII-coated vesicles, causes a
      defect in transport of selected proteins to the Golgi.
AB  - Emp24p is a type I transmembrane protein that is involved in secretory protein
      transport from the endoplasmic reticulum (ER) to the Golgi complex. A yeast
      mutant that lacks Emp24p (emp24 delta) is viable, but periplasmic invertase and
      the glycosylphosphatidyl-inositol-anchored plasma membrane protein Gas1p are
      delivered to the Golgi apparatus with reduced kinetics, whereas transport of
      alpha-factor, acid phosphatase and two vacuolar proteins is unaffected.
      Oligomerization and protease digestion studies of invertase suggest that the
      selective transport phenotype observed in the emp24 delta mutant is not due to a
      defect in protein folding or oligomerization. Consistent with a role in ER to
      Golgi transport, Emp24p is a component of COPII-coated, ER-derived transport
      vesicles that are isolated from a reconstituted in vitro budding reaction. We
      propose that Emp24p is involved in the sorting and/or concentration of a subset
      of secretory proteins into ER-derived transport vesicles.

PMID- 7729412
TI  - Folding and oligomerization of influenza hemagglutinin in the ER and the
      intermediate compartment.
AB  - Influenza hemagglutinin (HA) was used to analyze the stepwise folding and
      oligomeric assembly of glycoproteins in the early secretory pathway of living
      cells. In addition to mature trimers, six distinct maturation intermediates were
      identified. Of these, all the incompletely oxidized forms were located in the
      endoplasmic reticulum (ER) and associated with calnexin, a membrane-bound, lectin
      like ER chaperone. Once fully oxidized, the HA dissociated from calnexin as a
      monomer, which rapidly became resistant to dithiothreitol (DTT) reduction. Part
      of these extensively folded molecules moved as monomers into the intermediate
      compartment between the ER and the Golgi complex. Assembly of homotrimers
      occurred without calnexin-involvement within the ER and in the intermediate
      compartment. When anchor-free HA molecules were analyzed, it was found that they
      reach the DTT-resistant monomeric conformation but fail to trimerize. Taken
      together, the results provide a definition and intracellular localization of
      several intermediates in the conformational maturation of HA, including the
      immediate precursor for trimer assembly.

PMID- 7729413
TI  - A novel intermediate on the import pathway of cytochrome b2 into mitochondria:
      evidence for conservative sorting.
AB  - Cytochrome b2 is sorted into the intermembrane space of mitochondria by a
      bipartite N-terminal targeting and sorting presequence. In an attempt to define
      the sorting pathway we have identified an as yet unknown import intermediate.
      Cytochrome b2-dihydrofolate reductase (DHFR) fusion proteins were arrested in the
      presence of methotrexate (MTX) so that the DHFR domain was at the surface of the
      outer membrane while the N-terminus reached into the intermembrane space where
      the sorting signal was removed. This membrane-spanning, mature-sized species was
      efficiently chased into the mitochondria upon removal of MTX. Thus, an
      intermediate was generated which was exposed to the intermembrane space but was
      still associated with the inner membrane. This intermediate was also found upon
      direct import of cytochrome b2 and derived fusion proteins. These membrane-bound
      mature-sized cytochrome b2 species loop through the matrix and could be recovered
      in a complex with mt-Hsp70 and the inner membrane MIM44/ISP45, a component of the
      inner membrane import apparatus. This novel sorting intermediate can only be
      explained by a pathway in which cytochrome b2 passes through the matrix. The
      existence of such an intermediate is inconsistent with a pathway by which
      entrance of the mature part of cytochrome b2 into the matrix is stopped by the
      sorting sequence; however, its presence is fully consistent with the conservative
      sorting pathway.

PMID- 7729414
TI  - Fps1, a yeast member of the MIP family of channel proteins, is a facilitator for
      glycerol uptake and efflux and is inactive under osmotic stress.
AB  - The Saccharomyces cerevisiae FPS1 gene, which encodes a channel protein belonging
      to the MIP family, has been isolated previously as a multicopy suppressor of the
      growth defect of the fdp1 mutant (allelic to GGS1/TPS1) on fermentable sugars.
      Here we show that overexpression of FPS1 enhances glycerol production. Enhanced
      glycerol production caused by overexpression of GPD1 encoding glycerol-3
      phosphate dehydrogenase also suppressed the growth defect of ggs1/tps1 delta
      mutants, suggesting a novel role for glycerol production in the control of
      glycolysis. The suppression of ggs1/tps1 delta mutants by GPD1 depends on the
      presence of Fps1. Mutants lacking Fps1 accumulate a greater part of the glycerol
      intracellularly, indicating that Fps1 is involved in glycerol efflux. Glycerol
      uptake experiments showed that the permeability of the yeast plasma membrane for
      glycerol consists of an Fps1-independent component probably due to simple
      diffusion and of an Fps1-dependent component representing facilitated diffusion.
      The Escherichia coli glycerol facilitator expressed in a yeast fps1 delta mutant
      can restore the characteristics of glycerol uptake, production and distribution
      fully, but restores only partially growth of a ggs1/tps1 delta fps1 delta double
      mutant on glucose. Fps1 appears to be closed under hyperosmotic stress when
      survival depends on intracellular accumulation of glycerol and apparently opens
      rapidly when osmostress is lifted. The osmostress-induced High Osmolarity
      Glycerol (HOG) response pathway is not required for inactivation of Fps1. We
      conclude that Fps1 is a regulated yeast glycerol facilitator controlling glycerol
      production and cytosolic concentration, and might have additional functions.

PMID- 7729415
TI  - A Bcl-2-related gene is activated in avian cells transformed by the Rous sarcoma
      virus.
AB  - The oncoprotein p60v-src encoded by the Rous sarcoma virus (RSV) genome is the
      prototype of non-receptor tyrosine kinases. More than 50 targets of p60v-src have
      been described to date. However, the precise mechanisms of RSV transformation
      remain to be elucidated. Here, we present the study of a new v-src-activated
      gene, NR-13, which encodes a protein identified as a new member of the Bcl-2
      family. This protein is localized in the membrane with a pattern already observed
      with Bcl-2. In quail embryos, this gene is mainly expressed in neural and
      muscular tissues. Its expression is dramatically down-regulated after embryonic
      day 7 (E7) in the optic tectum. To evaluate a possible role for NR-13 in the
      control of apoptotic processes in this particular brain area, in situ
      hybridization and DNA ladder fractionation studies were performed to correlate NR
      13 expression with typical situations of apoptosis during brain development. Our
      results support the idea that RSV could activate anti-apoptotic functions of the
      host cell resulting in an increase of their lifespan, which could be particularly
      relevant to tumour formation.

PMID- 7729416
TI  - Epstein-Barr virus efficiently immortalizes human B cells without neutralizing
      the function of p53.
AB  - Epstein-Barr virus (EBV) efficiently converts resting human B cells into actively
      cycling, immortal, lymphoblastoid cell lines (LCLs). Here we show that LCLs
      expressing the full complement of latent viral genes are very sensitive to DNA
      damaging agents such as cisplatin. The response includes a rapid accumulation of
      the tumour suppressor protein p53 and induction of the cellular genes mdm2 and
      WAF1/p21. Although the levels of Bcl2 protein and Bax mRNA appear unaltered by
      the activation of p53, within 24 h the majority of cells undergo apoptosis. Over
      expression of wild-type p53 in an LCL also resulted in apoptosis; this was
      preceded by the dephosphorylation of the retinoblastoma gene product, pRb.
      Primary resting B cells showed no response to cisplatin and even after drug
      treatment, p53 remained undetectable. However, after infection with EBV, p53 gene
      expression was induced to a similar level to that found in mitogen-activated B
      cells. When the physiologically activated primary B cells were exposed to
      cisplatin, although p53 accumulated as in LCLs, the outcome was growth-arrest
      rather than gross cell death. We conclude that, in contrast to the transformation
      of fibroblasts by adenovirus, SV40 or HPV, when B cells become activated and
      immortalized by EBV they are sensitized to the p53-mediated damage response. When
      the resulting LCLs are treated with genotoxic agents such as cisplatin, they are
      unable to arrest like normal cells because they are driven to proliferate by EBV
      and consequently undergo apoptosis.

PMID- 7729417
TI  - Accumulation of wild-type p53 protein upon gamma-irradiation induces a G2 arrest
      dependent immunoglobulin kappa light chain gene expression.
AB  - The exposure of cells to DNA-damaging agents leads to the accumulation of wild
      type p53 protein. Furthermore, overexpression of the wild-type p53, mediated by
      transfection of p53-coding cDNA, induced cells to undergo apoptosis or cell
      differentiation. In this study we found that the gamma-irradiation that caused
      the accumulation of wild-type p53 in 70Z/3 pre-B cells induced, in addition to
      apoptosis, cell differentiation. This was manifested by the expression of the
      kappa light chain immunoglobulin gene that coincided with the accumulation of
      cells at the G2 phase. Overexpression of mutant p53 in 70Z/3 cells interferes
      with both differentiation and accumulation of cells at the G2 phase, as well as
      with apoptosis, which were induced by gamma-irradiation. Furthermore, the
      increment in the wild-type p53 protein level following gamma-irradiation was
      disrupted in the mutant p53 overproducer-derived cell lines. This suggests that
      mutant p53 may exert a dominant negative effect in all of these activities. Data
      presented here show that while p53-induced apoptosis is associated with the G1
      checkpoint, p53-mediated differentiation, which may be an additional pathway to
      escape the fixation of genetic errors, may be associated with the G2 growth
      arrest phase.

PMID- 7729418
TI  - An amino acid substitution in the Drosophila hopTum-l Jak kinase causes leukemia
      like hematopoietic defects.
AB  - Proteins of the Jak family of non-receptor kinases play important roles in
      mammalian hematopoietic signal transduction. They mediate the cellular response
      to a wide range of cytokines and growth factors. A dominant mutation in a
      Drosophila Jak kinase, hopscotchTumorous-lethal (hopTum-l), causes hematopoietic
      defects. Here we conduct a molecular analysis of hopTum-l. We demonstrate that
      the hopTum-l hematopoietic phenotype is caused by a single amino acid
      substitution of glycine to glutamic acid at residue 341. We generate a true
      revertant of the hopTum-l mutation, in which both the molecular lesion and the
      mutant hematopoietic phenotype revert back to wild type. We also examine the
      effects of the G341E substitution in transgenic flies. The results indicate that
      a mutant Jak kinase can cause leukemia-like abnormalities.

PMID- 7729419
TI  - Signal transfer through three compartments: transcription initiation of the
      Escherichia coli ferric citrate transport system from the cell surface.
AB  - Transport of ferric citrate into cells of Escherichia coli K-12 involves two
      energy-coupled transport systems, one across the outer membrane and one across
      the cytoplasmic membrane. Previously, we have shown that ferric citrate does not
      have to enter the cytoplasm of E. coli K-12 to induce transcription of the fec
      ferric citrate transport genes. Here we demonstrate that ferric citrate uptake
      into the periplasmic space between the outer and the cytoplasmic membranes is not
      required for fec gene induction. Rather, FecA and the TonB, ExbB and ExbD
      proteins are involved in induction of the fec transport genes independent of
      their role in ferric citrate transport across the outer membrane. The uptake of
      ferric citrate into the periplasmic space of fecA and tonB mutants via diffusion
      through the porin channels did not induce transcription of fec transport genes.
      Point mutants in FecA displayed the constitutive expression of fec transport
      genes in the absence of ferric citrate but still required TonB, with the
      exception of one FecA mutant which showed a TonB-independent induction. The
      phenotype of the FecA mutants suggests a signal transduction mechanism across
      three compartments: the outer membrane, the periplasmic space and the cytoplasmic
      membrane. The signal is triggered upon the interaction of ferric citrate with
      FecA protein. It is postulated that FecA, TonB, ExbB and ExbD transfer the signal
      across the outer membrane, while the regulatory protein FecR transmits the signal
      across the cytoplasmic membrane to FecI in the cytoplasm. FecI serves as a sigma
      factor which facilitates binding of the RNA polymerase to the fec transport gene
      promoter upstream of fecA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729420
TI  - Cell-type specificity during development in Bacillus subtilis: the molecular and
      morphological requirements for sigma E activation.
AB  - Development in Bacillus subtilis involves the formation of two cell types with
      activation of the transcription factors sigma F in the forespore and sigma E in
      the mother cell. Activation of sigma E is due to the processing of the inactive
      precursor pro-sigma E, which requires the putative protease SpoIIGA and the
      presence of active sigma F. We have introduced missense mutations altering the
      promoter recognition properties of sigma F. These mutations abolish pro-sigma E
      processing, suggesting that sigma F is involved through its transcriptional
      activity and that the processing machinery responds to a signal generated by the
      product(s) of some unidentified gene(s) transcribed in the forespore. The role of
      the septum in transducing this signal was investigated. Induction of sigma F
      during exponential growth in cells producing SpoIIGA and pro-sigma E led to a
      high level of processing and sigma E activity. Moreover, pro-sigma E was
      efficiently processed in a mutant strain blocked prior to septation and
      synthesizing sigma F in active form at the onset of sporulation. Therefore, the
      sporulation septum is not required for induction of pro-sigma E processing and
      pro-sigma E can be processed in the same cell in which sigma F is active. These
      results suggest that some unknown mechanism must exist to prevent sigma E from
      becoming active in the forespore.

PMID- 7729421
TI  - The sequence and binding specificity of UaY, the specific regulator of the purine
      utilization pathway in Aspergillus nidulans, suggest an evolutionary relationship
      with the PPR1 protein of Saccharomyces cerevisiae.
AB  - The uaY gene codes for a transcriptional activator mediating the induction of a
      number of unlinked genes involved in purine utilization in Aspergillus nidulans.
      Here we present the complete genomic and cDNA nucleotide sequence of this gene.
      The gene contains two introns. The derived polypeptide of 1060 residues contains
      a typical zinc binuclear cluster domain and shows a number of similarities with
      the PPR1 regulatory gene of Saccharomyces cerevisiae. These similarities are most
      striking in the putative linker and dimerization regions following the zinc
      cluster. Gel-shift and DNase I footprinting experiments have been carried out for
      three genes subject to UaY-mediated induction. The binding sequence is 5'-TCGG-6X
      CCGA, which is identical to the proposed PPR1 binding sites. Nevertheless, the
      identity of the base immediately 3' of the 5'-TCGG sequence clearly affects the
      affinity of the site. The site upstream of the uapA gene has been shown to be
      active in vivo. Binding to this site has been analysed by a number of
      interference techniques. There is an interesting chemical similarity between the
      co-inducer of the purine utilization pathway (uric acid) and that of the genes of
      the pyrimidine biosynthetic pathway (dihydroorotic acid) and we show that
      dihydroorotic acid can act as a poor inducer of at least one activity under UaY
      control. These striking similarities, together with the unique pattern of
      regulation of pyrimidine biosynthesis in S. cerevisiae, suggest that PPR1 evolved
      through recruitment into the pyrimidine biosynthetic pathway of an ancestral gene
      related to uaY.

PMID- 7729422
TI  - Yeast histone H4 and H3 N-termini have different effects on the chromatin
      structure of the GAL1 promoter.
AB  - Deletion of the histone H4 N-terminal residues 4-23 decreases activation of the
      GAL1 promoter as much as 20-fold, while deletion of histone H3 N-terminal
      residues 4-15 hyperactivates GAL1 approximately 3-fold. In an attempt to
      understand the mechanisms by which these two different events take place, we have
      examined the effects of the H4 and H3 lesions on GAL1 chromatin structure. The
      bacterial dam methylase, which methylates adenine residues of GATC sequences, was
      used as an in vivo probe for chromatin structure and both indirect end-labeling
      and ligation mediated PCR (LMPCR) analysis of micrococcal nuclease digestions
      were used to analyze chromatin in isolated nuclei. We show that while deletions
      of the H4 and H3 N-termini have similar effects on dam methylase access in the
      GAL1 coding region, the H4 N-terminal deletion uniquely alters dam access at a
      region near the TATA element. This change is independent of the transcriptional
      state of GAL1. In addition, LMPCR analysis of micrococcal nuclease digests of
      yeast nuclei demonstrate that H4 N-terminal deletion has unique effects on
      nuclease accessibility in the nucleosomal region upstream of the TATA element.
      Our results are consistent with the H4 N-terminus mediating activation of GAL1
      through its effect on the proximal promoter region near the TATA box. These data
      also suggest that the H3 N-terminus affects GAL1 hyperactivation through a
      different promoter element than that affected by H4.

PMID- 7729423
TI  - Incorporation of chromosomal proteins HMG-14/HMG-17 into nascent nucleosomes
      induces an extended chromatin conformation and enhances the utilization of active
      transcription complexes.
AB  - The role of chromosomal proteins HMG-14 and HMG-17 in the generation of
      transcriptionally active chromatin was studied in a Xenopus laevis egg extract
      which supports complementary DNA strand synthesis and chromatin assembly.
      Chromosomal proteins HMG-14/HMG-17 enhanced transcription from a chromatin
      template carrying a 5S rRNA gene, but not from a DNA template. The
      transcriptional potential of chromatin was enhanced only when these proteins were
      incorporated into the template during, but not after, chromatin assembly. HMG-14
      and HMG-17 stimulate transcription by increasing the activity, and not the
      number, of transcribed templates. They unfold the chromatin template without
      affecting the nucleosomal repeat or decreasing the content of histone B4. We
      suggest that HMG-14/HMG-17 enhance transcription by inducing an extended
      conformation in the chromatin fiber, perhaps due to interactions with histone
      tails in nucleosomes. By disrupting the higher order chromatin structure HMG
      14/HMG-17 increase the accessibility of target sequences to components of the
      transcriptional apparatus.

PMID- 7729424
TI  - TBP mutants defective in activated transcription in vivo.
AB  - The TATA box binding protein (TBP) plays a central and essential role in
      transcription initiation. At TATA box-containing genes transcribed by RNA
      polymerase II, TBP binds to the promoter and initiates the assembly of a
      multiprotein preinitiation complex. Several studies have suggested that binding
      of TBP to the TATA box is an important regulatory step in transcription
      initiation in vitro. To determine whether TBP is a target of regulatory factors
      in vivo, we performed a genetic screen in yeast for TBP mutants defective in
      activated transcription. One class of TBP mutants identified in this screen
      comprises inositol auxotrophs that are also defective in using galactose as a
      carbon source. These phenotypes are due to promoter-specific defects in
      transcription initiation that are governed by the upstream activating sequence
      (UAS) and apparently not by the sequence of the TATA element. The finding that
      these TBP mutants are severely impaired in DNA binding in vitro suggests that
      transcription initiation at certain genes is regulated at the level of TATA box
      binding by TBP in vivo.

PMID- 7729425
TI  - Downregulation of MHC class I expression due to interference with p105-NF kappa
      B1 processing by Ad12E1A.
AB  - We have previously demonstrated that expression of major histocompatibility
      complex (MHC) class I genes is repressed in baby rat kidney cells transformed by
      early region 1 of oncogenic adenovirus type 12 (Ad12E1). Reduced expression of
      MHC class I antigens contributes to the escape of Ad12-transformed cells from T
      cell-mediated immune surveillance and to tumour induction. In this study, we show
      that repression of MHC class I expression by Ad12E1A is mediated via the H2TF1
      element of the MHC class I promoter. This element binds NF kappa B and KBF1, two
      factors which play a major role in the regulation of MHC class I expression in
      vivo. In extracts from Ad12E1-transformed cells, binding of KBF1 and NF kappa B
      to the H2TF1 element is decreased. This is caused by reduced production of p50-NF
      kappa B1, the 50 kDa subunit shared by KBF1 and NF kappa B, due to interference
      with p105-NF kappa B1 processing by Ad12-13S-E1A protein. Overexpression of the
      p105-NF kappa B1 cDNA, or of a truncated p105-NF kappa B1 cDNA that codes for p50
      NF kappa B1, restores MHC class I expression in Ad12E1-transformed cells. These
      data demonstrate that downregulation of MHC class I expression in Ad12E1
      transformed cells is due to interference with processing of p105-NF kappa B1 by
      the Ad12-13S-E1A protein.

PMID- 7729426
TI  - Transcriptional activation by Myc is under negative control by the transcription
      factor AP-2.
AB  - The Myc protein binds to and transactivates the expression of genes via E-box
      elements containing a central CAC(G/A)TG sequence. The transcriptional activation
      function of Myc is required for its ability to induce cell cycle progression,
      cellular transformation and apoptosis. Here we show that transactivation by Myc
      is under negative control by the transcription factor AP-2. AP-2 inhibits
      transactivation by Myc via two distinct mechanisms. First, high affinity binding
      sites for AP-2 overlap Myc-response elements in two bona fide target genes of
      Myc, prothymosin-alpha and ornithine decarboxylase. On these sites, AP-2 competes
      for binding of either Myc/Max heterodimers or Max/Max homodimers. The second
      mechanism involves a specific interaction between C-terminal domains of AP-2 and
      the BR/HLH/LZ domain of Myc, but not Max or Mad. Binding of AP-2 to Myc does not
      preclude association of Myc with Max, but impairs DNA binding of the Myc/Max
      complex and inhibits transactivation by Myc even in the absence of an overlapping
      AP-2 binding site. Taken together, our data suggest that AP-2 acts as a negative
      regulator of transactivation by Myc.

PMID- 7729427
TI  - Cloning and characterization of hTAFII18, hTAFII20 and hTAFII28: three subunits
      of the human transcription factor TFIID.
AB  - We have cloned cDNAs encoding three novel TAFIIs [TATA-binding protein (TBP)
      associated factors] from the human (h) HeLa cell TFIID complexes hTAFII28,
      hTAFII20 and hTAFII18. hTAFII28 is a core hTAFII present in both of the
      previously described hTFIID species which either lack or contain hTAFII30 (hTFIID
      alpha and hTFIID beta respectively), and is the homologue of Drosophila
      (d)TAFII30 beta. hTAFII18 is a novel hTAFII which shows homology to the N
      terminal region of the yeast TAFIISPT3, but has no known Drosophila counterpart.
      In contrast to hTAFII28, hTAFII18 is a TFIID beta-specific hTAFII. hTAFII20 is
      the homologue of p22, an alternatively spliced form of dTAFII30 alpha (p32).
      Using a combination of protein affinity chromatography and cotransfection and
      immunoprecipitation assays, we have identified a series of in vitro and
      intracellular interactions among the novel hTAFIIs and between the novel hTAFIIs
      and hTAFII30 or TBP. We show that hTAFII28 interacts with hTAFII18 both in vitro
      and intracellularly; in contrast to its Drosophila homologue, hTAFII28 also
      interacts directly with TBP. Deletion analysis indicates that TBP and hTAFII18
      bind to distinct domains of hTAFII28. hTAFII18 also interacts with TBP, but it
      interacts more strongly with hTAFII28 and hTAFII30. The binding of hTAFII28 and
      hTAFII30 requires distinct domains of hTAFII18. As observed with the homologous
      Drosophila proteins, hTAFII20 interacts directly with TBP; however, additional
      interactions between hTAFII20 and hTAFII28 or hTAFII30 were detected. These
      results reveal differences not only in subunit composition, but also in the
      organization of dTFIID and hTFIID complexes.

PMID- 7729428
TI  - The solution structure of the RING finger domain from the acute promyelocytic
      leukaemia proto-oncoprotein PML.
AB  - Acute promyelocytic leukaemia (APL) has been ascribed to a chromosomal
      translocation event which results in a fusion protein comprising the PML protein
      and the retinoic acid receptor alpha. PML is normally a component of a nuclear
      multiprotein complex (termed ND10, Kr bodies, nuclear bodies, PML oncogenic
      domains or PODs) which is disrupted in the APL disease state. PML contains a
      number of characterized motifs including a Zn2+ binding domain called the RING or
      C3HC4 finger. Here we describe the solution structure of the PML RING finger as
      solved by 1H NMR methods at physiological pH with r.m.s. deviations for backbone
      atoms of 0.88 and 1.39 A for all atoms. Additional biophysical studies including
      CD and optical spectroscopy, show that the PML RING finger requires Zn2+ for
      autonomous folding and that cysteines are used in metal ligation. A comparison of
      the structure with the previously solved equine herpes virus IE110 RING finger,
      shows significant differences suggesting that the RING motif is structurally
      diverse. The role of the RING domain in PML nuclear body formation was tested in
      vivo, by using site-directed mutagenesis and immunofluorescence on transiently
      transfected NIH 3T3 cells. Independently mutating two pairs of cysteines in each
      of the Zn2+ binding sites prevents PML nuclear body formation, suggesting that a
      fully folded RING domain is necessary for this process. These results suggest
      that the PML RING domain is probably involved in protein-protein interactions, a
      feature which may be common to other RING finger domains.

PMID- 7729430
TI  - Site-specific recombination in the replication terminus region of Escherichia
      coli: functional replacement of dif.
AB  - The replication terminus region of the Escherichia coli chromosome encodes a
      locus, dif, that is required for normal chromosome segregation at cell division.
      dif is a substrate for site-specific recombination catalysed by the related
      chromosomally encoded recombinases XerC and XerD. It has been proposed that this
      recombination converts chromosome multimers formed by homologous recombination
      back to monomers in order that they can be segregated prior to cell division.
      Strains mutant in dif, xerC or xerD share a characteristic phenotype, containing
      a variable fraction of filamentous cells with aberrantly positioned and sized
      nucleoids. We show that the only DNA sequences required for wild-type dif
      function in the terminus region of the chromosome are contained within 33 bp
      known to bind XerC and XerD and that putative active site residues of the Xer
      recombinases are required for normal chromosome segregation. We have also shown
      that recombination by the loxP/Cre system of bacteriophage P1 will suppress the
      phenotype of a dif deletion strain when loxP is inserted in the terminus region.
      Suppression of the dif deletion phenotype did not occur when either dif/Xer or
      loxP/Cre recombination acted at other positions in the chromosome close to oriC
      or within lacZ, indicating that site-specific recombination must occur within the
      replication terminus region in order to allow normal chromosome segregation.

PMID- 7729429
TI  - Absolute dependence on kappa B responsive elements for initiation and Tat
      mediated amplification of HIV transcription in blood CD4 T lymphocytes.
AB  - The role of NF-kappa B-dependent signals in activating the transcriptional
      activity of the HIV regulatory region (LTR) was analyzed by systematic comparison
      of HIV LTR activity in human CD4 T cells purified from peripheral blood and a
      transformed lymphoblastoid T cell line. In normal CD4 T cells we also analyzed
      the role played by the viral kappa B responsive elements in HIV replication.
      Analysis of nuclear extracts of resting, normal T lymphocytes revealed the
      presence of the p50, but not the p65, NF-kappa B subunit and the induction by
      phorbol esters of bona fide (p50-p65) NF-kappa B complexes. In parallel, we
      observed clear enhancer-dependent HIV LTR transactivation comparable in intensity
      with that observed in lymphoblastoid cells. We show that unstimulated CD4 T
      lymphocytes offer a cellular environment of very low permissivity to HIV LTR
      functioning. This was in sharp contrast to the high spontaneous LTR activity
      observed in lymphoblastoid T cells, where LTR activity was essentially
      independent of kappa B-responsive elements. Due to the low basal LTR activity in
      resting T lymphocytes, NF-kappa B-dependent transactivation was a sine qua non
      event for induction of the HIV LTR. Surprisingly, even the function of HIV Tat in
      resting CD4 T lymphocytes was found to be absolutely dependent on LTR kappa B
      responsive elements. The relevance of these observations obtained in transient
      transfections was confirmed by the incapacity of blood CD4 T lymphocytes infected
      with an HIV infectious provirus carrying critical point mutations in the kappa B
      responsive elements to show any detectable transcriptional activity upon cell
      activation and prolonged culture in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729431
TI  - A novel type of interaction between cruciform DNA and a cruciform binding protein
      from HeLa cells.
AB  - We recently identified and enriched a protein (CBP) from HeLa cells with binding
      specificity for cruciform-containing DNA. We have now studied the interaction of
      CBP with stable cruciform DNA molecules containing the 27 bp palindrome of SV40
      on one strand and an unrelated 26 bp palindrome on the other strand by hydroxyl
      radical footprinting. The CBP-DNA interaction is localized to the four-way
      junction at the base of the cruciforms. CBP appears to interact with the elbows
      of the junctions in an asymmetric fashion. Upon CBP binding, structural
      distortions were observed in the cruciform stems and in a DNA region adjacent to
      the junction. These features distinguish CBP from other cruciform binding
      proteins, which bind symmetrically and display exclusively either contacts with
      the DNA backbone or structural alterations in the DNA.

PMID- 7729432
TI  - Fluid distribution and tissue thickness changes in 29 men during 1 week at
      moderate altitude (2,315 m).
AB  - To quantify fluid distribution at a moderate altitude (2,315 m) 29 male subjects
      were studied with respect to tissue thickness changes [front (forehead), sternum,
      tibia], changes of total body water, changes of plasma volume, total protein
      concentrations (TPC), colloid osmotic pressure (COP), and electrolytes. Tissue
      thickness at the forehead showed a significant increase from 4.14 mm to 4.41 mm
      48 h after ascent to the Rudolfshuette (2,315 m) (P < 0.05). At 96 h after ascent
      the tissue thickness at the tibia was decreased to 1.33 mm compared to the
      control value of 1.59 mm (P < 0.01). Body mass increased from 75.5 kg (control)
      to 76.2 kg on the last day (P < 0.05) and body water from 44.21 to 45.01 during
      the week (P < 0.01). The accumulation fluid in the upper part of the body was
      paralleled by a decrease in TPC and COP. At 48 h after the ascent COP dropped
      from 29.5 mmHg to 27.5 mmHg (P < 0.01). After 96 h at moderate altitude COP was
      still significantly decreased compared to the control level. At 1.5 h after the
      return from the Rudolf-shuette in Saalfelden (744 m) COP was back to the control
      values. The TPC also showed an initial drop from 7.75 g.dl-1 to 7.48 g.dl-1 after
      48 h at altitude and remained below the control value during the whole week (P <
      0.01). It seems from our study that even with exposure to moderate altitude
      measurable fluid shifts to the upper part of the body occurred which were
      detected by our ultrasound method.

PMID- 7729433
TI  - Knee extension torque and intramuscular pressure of the vastus lateralis muscle
      during eccentric and concentric activities.
AB  - The objectives of this study were to determine whether the occurrence of delayed
      onset muscle soreness (DOMS) for the vastus lateralis muscle was associated with
      elevated intramuscular pressure (IMP); and to assess, whether high eccentric
      forces occurred at an increased muscle length (as determined by joint angle).
      Therefore, peak knee extension torque, peak IMP of the vastus lateralis muscle,
      and the joint angle at which peak torque (JAPT) occurred were determined in eight
      male subjects during repetitive eccentric and concentric activities until fatigue
      occurred. Peak torque was significantly higher for eccentric compared to
      concentric activity (P < 0.01) and declined significantly for both activities (P
      < 0.01) throughout the protocols. When comparing the start (prior to fatigue) to
      the end (fatigue state), mean torque for eccentric activity declined from 191 to
      147 (N.m) and for concentric activity declined from 166 to 104 (N.m). In
      contrast, peak IMP was not significantly different between the types of activity
      and did not change significantly with time. At the start and the end, the mean
      IMP remained constant for eccentric activity at 54 mmHg (7.2 kPa) but for
      concentric activity was 78 mmHg (10.4 kPa) and 96 mmHg (12.8 kPa), respectively.
      All the subjects, however, experienced DOMS of the vastus lateralis muscle
      exclusively for the eccentric activity leg. The JAPT was not different between
      activity types and did not change significantly with time; however, a significant
      interaction between activity type and time was observed (P = 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7729434
TI  - Longitudinal study of the effect of high intensity weight training on aerobic
      capacity.
AB  - To investigate the effect of a long-term weight lifting programme characterized
      by high intensity, low repetition and long rest period between sets on maximal
      oxygen consumption (VO2max) and to determine the advantage of this programme
      combined with jogging, 26 male untrained students were involved in weight
      training for a period of 3 years. The VO2max and body composition of the subjects
      were examined at beginning, 1 year, 2 years (T2), and 3 years after (T3)
      training. Of the group, 19 subjects performed the weight lifting programme 5 days
      each week for 3 years (W-group), 4 subjects performed the same weight lifting
      programme for 3 years with an additional running programme consisting of 2 miles
      of jogging once a week during the 3rd year (R1-group), and 3 subjects performed
      the weight lifting programme during the 1st year and the same combined jogging
      and weight lifting programme as the R1-group during the 2nd and 3rd years (R2
      group). The average VO2max relative to their body mass of the W-group decreased
      significantly during the 1st year, followed by an insignificant decrease in the
      2nd year and a levelling off in the 3rd year. The average VO2max of the W-group
      at T2 and T3 was 44.2 and 44.1 ml.kg-1.min-1, respectively. The tendency of
      VO2max changes in the R1- and R2-groups was similar to the W-group until they
      started the jogging programme, after which they recovered significantly to the
      initial level within a year of including that programme, and they then levelled
      off during the next year. Lean body mass estimated from skinfold thicknesses had
      increased by about 8% after 3 years of weight lifting. The maximal muscle
      strength, defined by total olympic lifts (snatch, and clean and jerk), of these
      three groups increased significantly and there was no significant difference
      among the amounts of the increase in the three groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7729435
TI  - Differences in muscle sympathetic nerve response to isometric exercise in
      different muscle groups.
AB  - The aim of this study was to examine the effects of muscle fibre composition on
      muscle sympathetic nerve activity (MSNA) in response to isometric exercise. The
      MSNA, recorded from the tibial nerve by a microneurographic technique during
      contraction and following arterial occlusion, was compared in three different
      muscle groups: the forearm (handgrip), anterior tibialis (foot dorsal
      contraction), and soleus muscles (foot plantar contraction) contracted separately
      at intensities of 20%, 33% and 50% of the maximal voluntary force. The increases
      in MSNA relative to control levels during contraction and occlusion were
      significant at all contracting forces for handgrip and at 33% and 50% of maximal
      for dorsal contraction, but there were no significant changes, except during
      exercise at 50%, for plantar contraction. The size of the MSNA response
      correlated with the contraction force in all muscle groups. Pooling data for all
      contraction forces, there were different MSNA responses among muscle groups in
      contraction forces (P = 0.0001, two-way analysis of variance), and occlusion
      periods (P = 0.0001). The MSNA increases were in the following order of
      magnitude: handgrip, dorsal, and plantar contractions. The order of the fibre
      type composition in these three muscles is from equal numbers of types I and II
      fibres in the forearm to increasing number of type I fibres in the leg muscles.
      The different MSNA responses to the contraction of different muscle groups
      observed may have been due in part to muscle metaboreflex intensity influenced by
      their metabolic capacity which is related to by their metabolic capacity which is
      related to the fibre type.

PMID- 7729436
TI  - Differences in mechanical efficiency between power- and endurance-trained
      athletes while jumping.
AB  - Mechanical efficiency (ME) of jumping exercises was compared between power
      trained (n = 11) and endurance-trained athletes (n = 10) using both a
      biomechanical and a physiological approach. In drop jumps and in stretch
      shortening cycle exercise on a special sledge (sledge jumps), the subjects
      performed 60 muscle actions from a dropping height of optimum minus 40 cm (O-40),
      as well as from dropping heights of optimum (O) and optimum plus 40 cm (O + 40).
      Thus, they were tested in six different tests which lasted for a total of 3 min
      for each. The mean ME values in the drop jumps from the lowest dropping height
      upwards were as follows: 23.8 (SD 5.3)%, 35.5 (SD 10.8)% and 39.2 (SD 6.6)% for
      the power group, and 30.8 (SD 6.5)%, 37.5 (SD 8.7)% and 41.4 (SD 7.0)% for the
      endurance group. In the sledge jumps the ME values were 37.0 (SD 5.6)%, 48.4 (SD
      4.0)% and 54.9 (SD 8.5)% for the power group, and 40.2 (SD 5.9)%, 46.9 (SD 5.7)%
      and 58.5 (SD 5.5)% for the endurance group. As can be seen, the ME values
      increased with increasing stretch load. However, the groups did not differ from
      each other except in the drop jump condition of O-40 (P < 0.05). The higher power
      (P < 0.001) among the power athletes in every measured condition was associated
      with a faster rate of electromyogram development during the pre-activity, and
      smoother muscle activity patterns in the ground contact.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7729437
TI  - Measurement of muscle fibre displacement during contraction by real-time
      ultrasonography in humans.
AB  - The contact point (P) made by both the echoes of the aponeurosis and from
      interspaces among fascicles of the tibialis anterior muscle was detected by real
      time ultrasound scanning in 12 adults. Movement in the location of P was observed
      during muscle contraction and its displacement was related to changes in ankle
      joint angles (r = 0.81, P < 0.01), i.e., P shifted proximally when the ankle
      joint was dorsiflexed. There was also a significant positive correlation between
      the degree of dorsiflexion and the velocity related to the change in location of
      P (r = 0.84, P < 0.01). Ultrasound measurements of the displacement and the
      velocity of P were reproducible as there was no variation noticed among
      measurements on different days. It is suggested from these results that the
      displacement of P reflected changes in muscle length during contraction and that
      this amount of change corresponded to changes in joint angles.

PMID- 7729438
TI  - Growth and immobilization effects on sarcomeres: a comparison between
      gastrocnemius and soleus muscles of the adult rat.
AB  - The effects of growth and limb immobilization on muscle mass, total physiological
      cross-section (PC), the number of sarcomeres in series and the length of
      sarcomere components were investigated in the soleus muscle (SOL) and compared to
      previously obtained data on gastrocnemius (GM) muscles of rats between age 10 and
      16 weeks. For SOL this period of growth was reflected in an increased muscle mass
      and PC. No such increases were found for GM. In contrast, immobilization caused
      severe atrophy of fibres of both muscles. Compared to the value at the start of
      the immobilization, it was found that the fast twitch muscle (GM) atrophied more
      than the typically slow twitch one (SOL). The number of sarcomeres in series
      within fibres increased after growth and decreased after immobilization of SOL.
      For fibres of GM no such changes were observed. Muscle architecture is proposed
      as an important factor for the explanation of the results concerning the number
      of sarcomeres in series and those arranged in parallel. Due to the difference in
      muscle architecture, GM being more pennate than SOL, during growth, it is thought
      that increases in bone length affect the length of fibres of SOL more than those
      of GM. During immobilization, atrophy of fibres of GM was sufficient for the
      muscle length adaptation to meet the muscle length change induced by
      immobilization but in SOL, atrophy had to be accompanied by decreases in the
      number of sarcomeres in series to achieve adequate muscle length adaptation.

PMID- 7729439
TI  - Aerobic and anaerobic contribution to Wingate test performance in sprint and
      middle-distance runners.
AB  - We investigated the aerobic and anaerobic contributions to performance during the
      Wingate test in sprint and middle-distance runners and whether they were related
      to the peak aerobic and anaerobic performances determined by two commonly used
      tests: the force-velocity test and an incremental aerobic exercise test. A group
      of 14 male competitive runners participated: 7 sprinters, aged 20.7 (SEM 1.3)
      years, competing in 50, 100 and 200-m events and 7 middle-distance runners, aged
      20.0 (SEM 1.0) years, competing in 800, 1,000 and 1,500 m-events. The oxygen
      uptake (VO2) was recorded breath-by-breath during the test (30 s) and during the
      first 20 s of recovery. Blood samples for venous plasma lactate concentrations
      were drawn at rest before the start of the test and during the 20-min recovery
      period. During the Wingate test mean power (W) was determined and three values of
      mechanical efficiency, one individual and two arbitrary, 16% and 25%, were used
      to calculate the contributions of work by aerobic (Waer,ind,16%,25%) and
      anaerobic (Wan,ind,16%,25%) processes. Peak anaerobic power (Wan,peak) was
      estimated by the force-velocity test and maximal aerobic energy expenditure
      (Waer,peak) was determined during an incremental aerobic exercise test. During
      the Wingate test, the middle-distance runners had a significantly greater VO2
      than the sprinters (P < 0.001), who had significantly greater venous plasma
      lactate concentrations (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729440
TI  - Seasonal variation in sweating responses of older and younger men.
AB  - Eight older (60-65 years) and six younger (20-25 years) men were exposed to a
      standard heat stress for 60 min in summer, autumn, winter, and spring. The test
      consisted of placing the lower legs and feet in a 42 degrees C water bath while
      sitting in constant environmental conditions (30 degrees C and 45% relative
      humidity). The increase of rectal temperature (delta Tre) was significantly
      greater (P < 0.05) in autumn, winter, and spring than in summer for the older
      group, but significantly greater only in winter than in summer for the younger
      group (P < 0.05). The delta Tre was greater for the older group in all seasons,
      but of significance only in autumn and spring (P < 0.01). There were no
      significant season-related differences for metabolic heat production (M) and mean
      skin temperature (Tsk) during the heat test in the respective groups, although
      the M and Tsk were lower for the older group in all seasons (P < 0.01). In the
      older group total body sweating rate (msw) divided by delta Tre (total msw/delta
      Tre) decreased from summer to winter (P < 0.02) and did not differ between winter
      and spring, whereas total msw/delta Tre in the younger group increased in spring
      after decreasing from autumn to winter (P < 0.03). The variations of the value,
      local sweating rate on the back and thigh divided by delta Tre (back msw/delta
      Tre and thigh msw/delta Tre), were similar to those of the total msw/delta Tre in
      each group, except for back msw/delta Tre in the younger group, which did not
      increase from winter to spring.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729441
TI  - The physical demands of riding in National Hunt races.
AB  - Heart rate (fc) and post-competition blood lactate concentration ([La+]) were
      studied in seven male professional National Hunt jockeys over 30 races. The fc
      response for individual races followed a similar pattern for all subjects. The
      mean peak fc recorded during competition was 184 beats.min-1 (range 162-198
      beats.min-1) with average fc during the races ranging from 136 to 188 beats.min
      1. During consecutive races the recovery fc did not return to resting values. The
      mean [La+] was 7.1 mmol.l-1 (range 3.5-15.0 mmol.l-1). The conclusions of this
      study suggest that riding in National Hunt races is a physically demanding
      occupation. The muscular activity in this profession requires a high metabolic
      drive and produces a significant cardiorespiratory response.

PMID- 7729442
TI  - Effect of a low-carbohydrate diet on plasma and sweat ammonia concentrations
      during prolonged nonexhausting exercise.
AB  - The purpose of this investigation was to examine the effect of low body glycogen
      stores on plasma ammonia concentration and sweat ammonia excretion during
      prolonged, nonexhausting exercise of moderate intensity. On two occasions seven
      healthy untrained men pedalled on a cycle ergometer for 60 min at 50% of their
      predetermined maximal O2 uptakes (VO2max) firstly, following 3 days on a normal
      mixed diet (N-diet) (60% carbohydrates, 25% fat and 15% protein) and secondly,
      following 3 days on a low-carbohydrate diet (LC-diet) (less than 5%
      carbohydrates, 50% fat and 45% protein) of equal energy content. Blood was
      collected from the antecubital vein immediately before, at 30th and at 60th min
      of exercise. Sweat was collected from the hypogastric region using gauze pads. It
      was shown that plasma ammonia concentrations after the LC-diet were higher than
      after the N-diet at both the 30th and 60th min of exercise. Sweat ammonia
      concentration and total ammonia loss through the sweat were also higher after the
      LC-diet. The higher ammonia concentrations in plasma and sweat after the LC-diet
      would seem to indicate an increased ammonia production, which may be related to
      reduced initial carbohydrate stores.

PMID- 7729443
TI  - Association between heart rate variability and training response in sedentary
      middle-aged men.
AB  - The effect of exercise training on heart rate variability (HRV) and improvements
      in peak oxygen consumption (VO2peak) was examined in sedentary middle-aged men.
      The HRV and absolute and relative VO2peak of training (n = 19) and control (n =
      15) subjects were assessed before and after a 24-session moderate intensity
      exercise training programme. Results indicated that with exercise training there
      was a significantly increased absolute and relative VO2peak (P < 0.005) for the
      training group (12% and 11% respectively) with no increase for the control group.
      The training group also displayed a significant reduction in resting heart rate;
      however, HRV remained unchanged. The trained subjects were further categorized
      into high (n = 5) and low (n = 5) HRV groups and changes in VO2peak were
      compared. Improvements in both absolute and relative VO2peak were significantly
      greater (P > 0.005) in the high HRV group (17% and 20% respectively) compared to
      the low HRV group (6% and 1% respectively). The groups did not differ in mean
      age, pretraining oxygen consumption, or resting heart rate. These results would
      seem to suggest that a short aerobic training programme does not alter HRV in
      middle-aged men. Individual differences in HRV, however, may be associated with
      VO2peak response to aerobic training.

PMID- 7729444
TI  - Adjustment of metabolism, catecholamines and beta-adrenoceptors to 90 min of
      cycle ergometry.
AB  - Adrenaline infusion of 0.1 microgram.kg-1.min-1 in healthy volunteers results in
      an increase of hepatic glucose production, an increase of the absolute number of
      occupied beta-adrenoceptors and specific changes in metabolism. To compare these
      effects with the changes induced by an endogenous catecholamine release, we
      investigated healthy volunteers during cycle ergometry. After fasting at least 14
      h seven healthy subjects exercised for 90 min at an intensity of 20% below their
      individual anaerobic threshold. The rate of glucose production as well as the
      turnover rates of alanine and leucine were calculated using stable isotope
      tracers. High and low affinity beta-adrenergic binding sites on lymphocytes were
      determined by an equilibrium binding assay with (-)125 Iodocyanopindolol. After
      90 min of cycling the rate of appearance of glucose increased significantly from
      means of 2.0 (SD 0.2) to 2.65 (SD 0.50) mg.kg-1.min-1 with unchanged blood
      concentrations of glucose and lactate. The flux of the amino acids alanine and
      leucine decreased significantly from means of 0.91 (SD 0.21) to 0.62 (SD 0.14)
      mg.kg-1.min-1 and from 0.40 (SD 0.05) to 0.32 (SD 0.04) mg.kg-1.min-1,
      respectively. The mean free fatty acid concentration increased significantly from
      0.65 (SD 0.33) to 1.27 (SD 0.45) mmol.l-1 during the endurance trial. The
      increase of glucose turnover and the decrease of amino acid flux point to a
      metabolic shift towards enhanced utilization of free fatty acids. Adrenaline and
      noradrenaline concentrations showed a moderate but significant increase from
      means of 0.61 (SD 0.20) to 0.99 (SD 0.36) nmol.l-1 and from 2.27 (SD 0.75) to
      3.46 (SD 0.38) nmol.l-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729445
TI  - Age predicts cardiovascular, but not thermoregulatory, responses to humid heat
      stress.
AB  - Cross-section comparisons of the effect of age on physiological responses to heat
      stress have yielded conflicting results, in part because of the inability to
      separate chronological age from factors which change in concert with the
      biological aging process. The present study was designed to examine the relative
      influence of age on cardiovascular and thermoregulatory responses to low
      intensity cycle exercise (60 W for 1 h) in a warm humid environment (35 degrees
      C, 80% relative humidity). Specifically, the relative importance of age compared
      to other individual characteristics [maximal oxygen uptake (VO2max), physical
      activity level, anthropometry, and adiposity] was determined by multiple
      regression analysis in a heterogeneous sample of 56 subjects in which age (20-73
      years) and VO2max (1.86-4.44 l.min-1) were not interrelated. Dependent variables
      (with ranges) included final values of thermoregulatory responses [rectal
      temperature (Tre, 37.8-39.2 degrees C), calculated heat storage (S, 3.4-8.1 J.g
      1), sweat loss (238-847 g.m-2)] and cardiovascular responses [heart rate (HR, 94
      176 beats.min-1), forearm blood flow (FBF, 5.3-31.3 ml.100 ml-1.min-1), mean
      arterial blood pressure (MAP, 68-122 mmHg), and forearm vascular conductance (FVC
      = FBF.MAP-1, 0.06-0.44 ml.100 ml-1.min-1.mmHg-1). Age had no significant
      influence on Tre, S, or sweat loss, all of which were closely related to VO2max.
      On the other hand, HR, MAP, FBF, and FVC were related to both age and VO2max.
      Anthropometric variables and adiposity had secondary, but statistically
      significant, effects on MAP, FBF, FVC, and sweat loss.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7729446
TI  - Polymerase chain reaction for detection of Borrelia burgdorferi DNA in skin
      lesions of early and late Lyme borreliosis.
AB  - The aim of this study was to evaluate the polymerase chain reaction (PCR) as a
      diagnostic tool for Lyme borreliosis on large numbers of samples from clinically
      well-defined cases of early and late cutaneous borreliosis. Skin biopsy specimens
      from patients with erythema migrans and acrodermatitis chronica atrophicans were
      analysed blindly together with an equal number of control biopsies. Using two
      different dilutions of each DNA specimen increased the number of total positives
      detected. All of the 76 control biopsies were PCR negative. Biopsy specimens from
      18 of 26 (69%) erythema migrans lesions and from 22 of 36 (61%) acrodermatitis
      chronica atrophicans lesions were PCR positive. Fourteen post-therapy biopsies
      from patients with acrodermatitis chronica atrophicans were all negative,
      supporting the opinion that antibiotic therapy is successful in this chronic
      manifestation of Lyme borreliosis.

PMID- 7729447
TI  - Discrepancies in susceptibility test results for imipenem employing different in
      vitro test methods and DIN 58,940 breakpoints.
AB  - During the first half of 1993, bacteria that were isolated from clinical
      materials and found to have intermediate susceptibility by an agar dilution
      breakpoint method were collected in a large service laboratory in Germany. All of
      these isolates were gram-negative bacteria. They were re-tested employing full
      scale agar dilution, broth microdilution, E-test and agar diffusion procedures.
      The results obtained indicated that 76.9% of the isolates were actually
      susceptible upon re-testing with a reference agar dilution technique. The reason
      for the discrepant results remained largely unclear. There was a high correlation
      between agar dilution and E-test results while the agreement with broth
      microdilution and agar diffusion was less satisfactory. It is suggested that the
      breakpoint between susceptible and intermediate categories currently recommended
      by DIN 58,940 (standard set by Deutsches Institut fur Normung e.V.) be raised to
      reduce erroneous interpretations of minimum inhibitory concentrations.

PMID- 7729448
TI  - Induction of beta-lactamase by cefoxitin in anaerobic intestinal microflora.
AB  - Beta-lactamases produced by two anaerobic bacterial strains, Bacteroides ovatus
      Ax34:1 and Clostridium butyricum NBL3, were shown to be significantly inducible
      under anaerobic conditions in subinhibitory concentrations of cefoxitin. The
      induction ratio of beta-lactamase production for Bacteroides ovatus was 2.6 and
      for Clostridium butyricum 1.6. Incubation of faecal samples with different
      concentrations of cefoxitin did not result in any induction of beta-lactamase
      production. When adding a highly inducible aerobic strain (Citrobacter freundii
      F72:6, induction ratio of 26.5 in broth culture) to faecal samples, an induction
      ratio of 4.5 was reached. Faeces seem to inhibit beta-lactamase induction in
      aerobic and anaerobic bacteria. The inducible enzymes produced by the anaerobic
      strains did not have the same properties as beta-lactamases from aerobic
      inducible strains, according to substrate profiles and inhibition studies. The
      results of the present study indicate that increased levels of beta-lactamases in
      the normal intestinal microflora, which often are observed after administration
      of beta-lactam agents, are probably due to selection of stably derepressed
      mutants rather than to induction of beta-lactamase production.

PMID- 7729449
TI  - Detection of Legionella DNA in human and guinea pig urine samples by the
      polymerase chain reaction.
AB  - A detection system for Legionella DNA in urine samples based on the polymerase
      chain reaction (PCR) was developed and tested on infected guinea pigs and
      patients suffering from pneumonia. Results were compared with standard methods
      for diagnosis of Legionnaires' disease. A primer system was selected which
      amplifies a 108 bp DNA fragment of the 5S rRNA gene. The sensitivity of the PCR
      system was one femtogram of extracted Legionella DNA. Three methods were tested
      for pretreatment of urine samples. Of these, the Geneclean II kit (Bio 101, USA)
      gave the best results for artificially contaminated urine samples as well as
      those from infected guinea pigs or patients. Thirty-seven urine samples from 15
      guinea pigs intraperitoneally infected with either Legionella pneumophila
      serogroup 1, 3 and 6 or Legionella micdadei, 26 urine samples of 21 patients
      suffering from pneumonia, and 30 control samples of patients with urinary tract
      infection (UTI) were tested. Legionella DNA was detected in 29 of the guinea pig
      urine samples; whereas, urinary antigen detection using EIA was positive in only
      20 of the samples. PCR was also positive in the samples of 11 patients with
      pneumonia, 9 of which were confirmed by other microbiological methods, such as
      culture, direct fluorescent antibody test, urinary antigen detection and antibody
      testing. However, of the 30 control samples from patients with UTI, three samples
      yielded positive results. The results demonstrate that Legionella DNA is excreted
      in the urine of infected individuals and that the PCR shows a higher degree of
      sensitivity than EIA to the detection of soluble Legionella antigen in
      urine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729450
TI  - Nasopharyngeal carriage of Staphylococcus aureus and carriage of tetracycline
      resistant strains associated with HIV-seropositivity.
AB  - The aim of this prospective study was to investigate the relationship between
      carriage of antibiotic-resistant Staphylococcus aureus and infection with the
      human immunodeficiency virus (HIV). A total of 554 pernasal swabs was taken
      during a six-month period from 554 adult patients attending three outpatient
      clinics and from inpatients from a hospital in Nairobi, Kenya. Overall, 121 swabs
      (22%) yielded Staphylococcus aureus, there being significantly higher carriage in
      HIV-positive patients (71/264, 27%) than in HIV-negative patients (50/290, 17%);
      p = 0.008. Antimicrobial resistance rates were determined for 110 isolates and
      were high for penicillin (91%) and tetracycline (72%) and low for erythromycin
      (8%), methicillin (3%), gentamicin (5%) and chloramphenicol (0%). Genetic
      analysis showed plasmids in the range of 24-42 MDa to be associated with beta
      lactamase production and plasmids in the range of 3-5 MDa to be associated with
      resistance to tetracycline, erythromycin and trimethoprim. All nine erythromycin
      resistant strains were from HIV-positive patients (p = 0.02). There was a
      significant association of tetracycline resistance with HIV seropositivity (p =
      0.002). The association of HIV seropositivity with Staphylococcus aureus carriage
      and carriage of antibiotic-resistant strains against the background of the HIV
      epidemic are of relevance in individual patient care and raise concern for public
      health.

PMID- 7729451
TI  - Pulmonary toxicity during infusion of liposomal amphotericin B in two patients
      with acute leukemia.
AB  - Pulmonary toxicity with acute dyspnea occurred during infusion of a liposomal
      amphotericin B preparation (AmBisome) in two adult leukemic patients. The
      preparation was administered as a one hour infusion at a dose of 3 mg/kg body
      weight. Within 15 min after starting the infusion, both patients experienced
      sudden onset of dyspnea and chest tightness. Physical examination showed the
      patients to be anxious and restless with tachycardia and orthopnea but without
      other cardiopulmonary findings. No elevation of body temperature, rigors or
      chills were recorded. Symptoms disappeared within minutes after discontinuing the
      infusion. At present, the pathophysiologic mechanisms underlying these side
      effects are unknown.

PMID- 7729452
TI  - Frequency of toxic shock syndrome toxin- and enterotoxin-producing clinical
      isolates of Staphylococcus aureus.
AB  - In 183 clinical isolates of Staphylococcus aureus, toxic shock syndrome toxin was
      detected in 13.7%, enterotoxin A in 20.2%, enterotoxin B in 7.7%, enterotoxin C
      in 5.5% and enterotoxin D in 3.3%. Seventy-three (39.9%) of the strains were
      found to produce one or more toxins. Multiple secretion of toxins was rare (< 1%
      of all strains) except for the combinations enterotoxin A with toxic shock
      syndrome toxin and enterotoxin A with enterotoxin D. These combinations were
      observed at significantly higher frequencies (4.9% and 2.2%, respectively) than
      would have been expected from values calculated from respective individual
      frequencies (0.88% and 0.06%) (p < 0.0001). In comparison with Staphylococcus
      aureus strains isolated from miscellaneous material, Staphylococcus aureus blood
      culture isolates produced enterotoxin D in significantly larger amounts and at
      higher frequencies (p = 0.01 in both cases). These toxins might play an important
      pathogenic role in Staphylococcus aureus infections.

PMID- 7729453
TI  - Evaluation of the optimal number of faecal specimens in the diagnosis of
      cryptosporidiosis in AIDS and immunocompetent patients.
AB  - This study determines the optimal number of faecal samples that should be
      examined in order to minimize the occurrence of false-negative results in the
      diagnosis of cryptosporidiosis using routine techniques. A total of 23,023 faecal
      samples from 10,870 patients submitted for parasitological examination were
      processed by the formalin-ethyl acetate concentration technique and stained using
      a modified Ziehl-Neelsen method. Cryptosporidiosis was diagnosed in 232 patients
      (2.13%), 44 of whom were infected by HIV, the prevalence rate in this population
      group being 15.54%. The increase in the number of diagnoses obtained by the
      examination of n and (n-1) specimens was evaluated statistically. This study
      found that three is the optimal number of faecal samples that should be examined
      when cryptosporidiosis is suspected in immunocompetent patients; whereas, only
      two samples are required for diagnosing this protozoosis in AIDS patients.

PMID- 7729454
TI  - Endocarditis caused by Aerococcus urinae, a newly recognized pathogen.
AB  - Aerococcus urinae is a newly described pathogen. A case of Aerococcus urinae
      endocarditis is presented, the primary focus being a urinary tract infection. The
      diagnosis of endocarditis was supported by isolation of Aerococcus urinae from
      blood as well as from heart vegetations.

PMID- 7729455
TI  - Carriage of Streptococcus pyogenes among infants and toddlers attending day-care
      facilities in closed communities in southern Israel.
AB  - Infants and toddlers attending ten day-care facilities in closed communities in
      southern Israel were tested monthly for pharyngeal carriage of Streptococcus
      pyogenes and associated respiratory morbidity. Overall, the prevalence of
      Streptococcus pyogenes was 2.7% in infants and 8.4% in toddlers, reaching 8.5%
      and 17.8% in the two groups, respectively by midwinter. In 4 of 61 (6.6%) infants
      and 15 of 67 (22.4%) toddlers, the organism was recovered in more than one month
      (range 2 to 5 months). Streptococcus pyogenes in the pharynx was only associated
      with rhinitis during the spring and summer but not with other respiratory
      symptoms. During the study period, a mean of 0.9 strains were isolated in day
      care facilities attended by infants, while a mean of 2.1 strains were found in
      toddlers. Young children attending day-care facilities show early acquisition of
      Streptococcus pyogenes in the pharynx.

PMID- 7729456
TI  - Comparison of nasopharyngeal aspirates and throat swab specimens in a polymerase
      chain reaction-based test for Mycoplasma pneumoniae.
AB  - Nasopharyngeal aspirates and throat swab specimens were compared in a polymerase
      chain reaction (PCR)-based test for Mycoplasma pneumoniae. The pathogen was
      detected in 50% and 45% of throat swab specimens and aspirates, respectively.
      However, in specimens negative for Mycoplasma pneumoniae by PCR, amplification
      inhibitors were detected in 0% and 36% of throat specimens and aspirates,
      respectively. Further investigations confirmed that no throat specimens, but one
      quarter of aspirates, are likely to be rejected for containing inadequate
      respiratory material or excess amplification inhibitors. Because rejection of
      most of the unsuitable specimens is possible only after PCR, the use of aspirates
      is less cost-effective. This, and the reluctance to subject patients to
      aspiration, make the aspirate an inferior specimen for detection of Mycoplasma
      pneumoniae by PCR.

PMID- 7729457
TI  - Rapid detection of tuberculous and non-tuberculous mycobacteria by microscopic
      observation of growth on Middlebrook 7H11 agar.
AB  - The rate of recovery and time to the detection of mycobacteria in clinical
      specimens were measured in traditional egg-based media cultures and on
      Middlebrook 7H11 agar plate cultures using microcolony detection. In the 5438
      specimens processed, a total of 293 (5.4%) clinically relevant mycobacterial
      isolates were detected (Mycobacterium tuberculosis, n = 231; Mycobacterium avium
      complex, n = 60; Mycobacterium kansasii, n = 2). Of these, 227 (77%) and 237
      (81%) isolates were detected on Lowenstein-Jensen medium and Coletsos medium,
      respectively, and 265 (90%) isolates were detected on Middlebrook 7H11 plates
      examined microscopically. The detection time was shorter with the microcolony
      detection method. While the Lowenstein-Jensen and Coletsos media required an
      average of 23 and 25 days, respectively, for first detection of mycobacteria,
      microcolony detection on Middlebrook 7H11 required an average of only 12 days.
      For acid-fast, stain-positive specimens that were culture positive for
      Mycobacterium tuberculosis, the average interval to positivity was nine days for
      the microcolony method compared with 20 and 21 days for the Lowenstein-Jensen and
      Coletsos media, respectively. Microscopic detection on Middlebrook 7H11 agar
      plates is a rapid, accurate and inexpensive method of detecting Mycobacterium
      tuberculosis and other clinically important mycobacteria.

PMID- 7729458
TI  - Lack of effect of orally administered human serum immunoglobulin on the normal
      human oral and intestinal microflora.
AB  - The aim of this study was to investigate the influence of large doses of orally
      administered human IgG on the normal gastrointestinal microflora of healthy
      volunteers since human immunoglobulin has been tried as oral prophylaxis and
      therapy in gastrointestinal infections. Ten adult healthy volunteers received 10
      g of IgG orally, once daily for three consecutive days. Aerobic and anaerobic
      microorganisms were identified in the saliva and stool specimens, using
      morphological, biochemical and serological tests and gas-liquid chromatography.
      Although the immunoglobulin preparation contains antibodies against a variety of
      microorganisms, there were no significant changes in the numbers of different
      aerobic and anaerobic microorganisms due to the oral intake of the
      immunoglobulin. IgG may, therefore, be used against pathogens without disturbing
      the normal oral and intestinal microflora.

PMID- 7729459
TI  - Conventional viral cultures and shell vial assay for diagnosis of apparently
      culture-negative Coxiella burnetii endocarditis.
AB  - A patient with culture-negative endocarditis was diagnosed with Q fever
      endocarditis based on the results of serological tests and positive leukocyte
      cultures obtained using conventional viral cultures and the shell vial technique.
      This case report suggests that isolation of Coxiella burnetii from blood may
      allow better diagnostic and therapeutical evaluation of patients with Q fever
      endocarditis. The use of both conventional and shell vial viral cultures is
      recommended for the isolation of Coxiella burnetii from the blood of patients
      with apparently culture-negative endocarditis.

PMID- 7729460
TI  - Early-onset septicemia in a newborn due to a penicillin resistant pneumococcus
      probably transmitted during delivery.

PMID- 7729461
TI  - Patterns of antibiotic resistance among enterococcal strains isolated from
      clinical specimens and food in Poland.

PMID- 7729462
TI  - Prevalence of Coxiella burnetii infection among slaughterhouse workers in
      northern Spain.

PMID- 7729463
TI  - Anaerobic bacteraemia in an Australian teaching hospital.

PMID- 7729464
TI  - CD4+ T-lymphocytopenia in the elderly.

PMID- 7729465
TI  - New infective problems with old gram-positive pathogens: setting the stage.

PMID- 7729466
TI  - Glycopeptides in the treatment of staphylococcal infections.
AB  - Gram-positive bacteria are rapidly becoming the most important pathogens in
      nosocomial infections. In recent years, attention and concern have been focused
      on the gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis
      and Enterococcus faecalis. These microorganisms are well equipped to exert their
      pathogenic effects and to display virulence. Treatment of severe infections
      caused by gram-positive bacteria remains difficult because of the increase in
      infections caused by methicillin-resistant staphylococci, and this has renewed
      interest in the glycopeptide antibiotics, vancomycin and teicoplanin. According
      to National Nosocomial Infection Surveillance Study data, in 1989, 60% of
      coagulase-negative staphylococci and 22% of Staphylococcus aureus strains showed
      methicillin resistance. Among other factors, successful antimicrobial therapy
      depends on rapid and reliable antibiotic delivery to the infection site at a
      concentration adequate to inhibit the majority of infecting organisms.
      Glycopeptides may be important in the therapy of catheter-related infections,
      which are mainly caused by coagulase-negative staphylococci and Staphylococcus
      aureus.

PMID- 7729467
TI  - Multiply-resistant pneumococcus: therapeutic problems in the management of
      serious infections.
AB  - The control of penicillin-resistant pneumococci has become one of the more
      serious therapeutic challenges facing clinicians today. The occurrence and
      geographical coverage of these microorganisms have increased rapidly since they
      were first recognized in the late 1960s. They have now been reported from every
      continent, and in some regions can account for over 60% of the pneumococci
      isolated. An even greater concern is the propensity of penicillin-resistant
      pneumococci towards resistance to multiple antibiotics, including the
      cephalosporins and non-beta-lactam drugs. In areas where multiply-resistant
      strains are common, the therapeutic choices for the treatment of life-threatening
      infections may be limited to drugs which are either toxic for the patient or for
      which we are only beginning to gain clinical experience. As the importance of
      Streptococcus pneumoniae in meningitis continues to increase and multiply
      resistant strains become more widespread and entrenched, it is essential that the
      search for more well-tolerated and effective treatment regimens continues.
      However, unless the effect of antibiotics on the selection of these resistant
      pathogens is addressed and a more judicious approach towards drug use is taken;
      this resistance problem will continue well into the future.

PMID- 7729468
TI  - Invasive streptococci.
AB  - Before the introduction of antibiotics, serious infections caused by
      Streptococcus pyogenes (Lancefield Group A streptococci) were common. Before
      World War II, this bacterium was responsible for as many as 50% of postpartum
      deaths and was the major cause of death in patients with burns. Also common were
      the sequelae of streptococcal infections-rheumatic fever and post-streptococcal
      glomerulonephritis. With the use of penicillin, however, Streptococcus pyogenes
      was believed to be virtually eliminated as a pathogen. The organism was consigned
      to the history books, but not for long. In the mid-1980s, focal resurgences of
      rheumatic fever began to be reported from different areas in the USA, such as
      Salt Lake City, Utah. In such communities, where increases in cases of rheumatic
      fever had been reported, the serotypes M-1, 3, 5, 6 and 18 were isolated which,
      on culture, produced characteristic mucoid colonies. At the same time, reports of
      increases in invasive streptococcal disease began to surface in both the USA and
      Europe. Two syndromes were described; invasive streptococcal infection, occurring
      in previously healthy children and adults, commonly associated with septicaemia
      resulting from a deep focus of infection such as bone or lung; and streptococcal
      toxic shock syndrome, involving a cutaneous focus, accompanied by necrotizing or
      bullous soft tissue changes. Septicaemia is rare in streptococcal toxic shock
      syndrome, but the most characteristic feature is one of rapidly progressing multi
      organ failure. A high proportion of the strains of Streptococcus pyogenes
      associated with this condition are serotype M-1, and fatality rates approaching
      50% have been reported.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729469
TI  - Usefulness of pulsed-field gel electrophoresis in the epidemiological analysis of
      Staphylococcus aureus isolates with decreased susceptibility to teicoplanin.
AB  - Pulsed-field gel electrophoresis for analysis of comparatively mega-base sized
      chromosomal restriction fragments is an important molecular technique in the
      epidemiological study of a variety of nosocomial pathogens. The usefulness of
      this approach is demonstrated in the evaluation of Staphylococcus aureus isolates
      exhibiting decreased susceptibility to teicoplanin in two clinical settings:
      multiple cultures from a single patient and isolates from different patients
      within the same hospital.

PMID- 7729470
TI  - Enterococci: susceptibility patterns and therapeutic options.
AB  - Enterococci do not possess the common virulence factors found in many other
      bacteria, but they have a number of other characteristics which make them
      particularly pathogenic. These organisms are intrinsically resistant to a number
      of antimicrobial agents, including beta-lactams (penicillins and cephalosporins),
      polymyxins and the lincosamides. They are also tolerant to the bactericidal
      activity of penicillins and glycopeptides, and some of the group have acquired
      resistance to a number of other clinically important antimicrobial agents
      including ampicillin, aminoglycosides, chloramphenicol and erythromycin. Numerous
      national and international studies have demonstrated the changes in the
      antibiotic resistance of enterococci. Many strains now exhibit multiple drug
      resistance, the most important being high-level resistance to streptomycin and
      gentamicin. Organisms exhibiting this high-level resistance are usually resistant
      to all synergistic combinations of beta-lactam antibiotics and aminoglycosides.
      Ampicillin-resistant strains are now emerging, some of which are beta-lactamase
      producers. While resistance to glycopeptides remains rare, it is increasing
      dramatically in many areas of the world. As nosocomial isolates of enterococci
      have displayed resistance to essentially every useful antimicrobial agent, it is
      likely to become increasingly difficult to treat and control enterococcal
      infections. The glycopeptide antibiotics vancomycin and, particularly,
      teicoplanin are the only alternatives currently available. Although a
      bactericidal combination of antibiotics appears necessary only in endocarditis
      and meningitis and although knowledge of the prevalence of resistant strains can
      be used to guide the selection of appropriate therapy, optimal regimens for the
      treatment of infections caused by multiresistant strains have yet to be
      determined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729471
TI  - Fluoroquinolone resistance in staphylococci: new challenges.
AB  - Staphylococci show only marginal susceptibility to the newer fluoroquinolones.
      Minimum inhibitory concentrations (MICs) for susceptible strains usually range
      from 0.25 to 2.0 mg/l. As a single mutational event involving the gyrase target
      or permeability diminishes fluoroquinolone susceptibility fourfold on average,
      such a mutation in staphylococci would lead to a clinical level of resistance.
      Therefore, it is not surprising that in some institutions, the use of
      fluoroquinolones has been quickly followed by greatly increased prevalence of
      fluoroquinolone-resistant staphylococci. The greatest increase in resistance has
      been seen among methicillin-resistant staphylococci although increased prevalence
      of resistance among Staphylococcus saprophyticus and other methicillin
      susceptible staphylococci has also been reported. Clinical isolates of
      staphylococci recovered since the introduction of the fluoroquinolones fall into
      three fluoroquinolone susceptibility groups: susceptible (MIC < 0.5 mg/l),
      moderately resistant (MIC 0.5 to 4 mg/l) and highly resistant (MIC > 4 mg/l). The
      first group represents wild type strains while the second and third groups
      represent single- and multiple-step mutants, respectively. To prevent increasing
      prevalence of isolates in the second and third groups, it would be prudent to
      avoid use of quinolones whenever possible. However, when it is necessary, a
      fluoroquinolone, which achieves serum/tissue levels eight times the MIC of the
      infecting strain, should be used.

PMID- 7729472
TI  - Entamoeba histolytica: increase of enterotoxicity and of 53- and 75-kDa cysteine
      proteinases in a clone of higher virulence.
AB  - We compared the enterotoxicity and cysteine proteinases (CP) of the low-virulence
      Entamoeba histolytica HM1 strain with the highly virulent 1659 clone, derived
      from HM1 by hamster liver passages. Enterotoxicity of 50,000 freeze-thawed
      trophozoites was determined on 0.28-cm2 intestinal segments mounted in Ussing
      chambers; CP activity of Nonidet-P40 amebal lysates was assayed by gelatin-sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and carbobenzoxy-L-arginine-L
      arginyl-p-nitroaniline, a CP-specific substrate. Treatment of gerbil cecum
      segments with amebal lysates caused an immediate fall of their electrophysiologic
      properties (potential difference, short-circuit current, and transmural
      resistance) whose decay rates were clearly faster with 1659 than with HM1
      lysates. Nonimmune and immune antiamebic human sera and the CP-specific inhibitor
      E-64 (trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane) prevented the fall of
      the electrophysiologic properties. Gelatinases, less active in HM1 than in 1659
      trophozoites, were better preserved in lysates containing 10 mM p
      hydroxymercuribenzoate (pHMB) to prevent autoproteolysis: in lysates without pHMB
      nearly no gelatinase bands were observed in HM1 samples, whereas intense 30K,
      35K, 44K, and 75K bands were seen in 1659 samples; in lysates with pHMB only 53K
      and 75K bands were found that were much more intense in 1659 samples, 75K being
      barely visible in HM1 samples. The overall CP activity was 17 times higher in
      1659 than in HM1 lysates, was inhibited by E-64 (mean inhibitory dose, 20
      microM), was stimulated by 2-mercaptoethanol (ME) 3.7 times in HM1 and 2.4 times
      in 1659 lysates, and was reactivated by ME in lysates containing pHMB. Most of
      the CP activity in HM1 lysates sedimented at 15,600g but predominated in 1659
      supernatants. The increase of E. histolytica virulence thus correlates with a
      remarkable increase both of in vitro enterotoxicity and of two CPs (53K and 75K),
      suggesting that these proteinases are significant pathogenicity factors.

PMID- 7729473
TI  - Interactions of atovaquone with other antimalarial drugs against Plasmodium
      falciparum in vitro.
AB  - A series of Plasmodium falciparum in vitro drug sensitivity studies were
      conducted in order to evaluate atovaquone in combination with other antimalarial
      drugs and thus to identify a potential partner for a fixed combination. The
      derived isobolograms indicated that drug interactions ranged from antagonism
      through addition to synergy. Of particular note were the quinolines and
      artemisinin analogues, which were all antagonistic, and the biguanides and
      tetracycline, which showed synergy. Proguanil emerged as the most promising of
      the current antimalarials as a partner for atovaquone in a fixed combination,
      with tetracycline as back-up.

PMID- 7729474
TI  - Trypanosoma brucei brucei: uptake and metabolism of pyridoxine and pyridoxal.
AB  - The uptake and metabolism of the B6 vitamers pyridoxine and pyridoxal by T.
      brucei (TREU 55) was investigated. The results show that these vitamers are taken
      up by simple diffusion followed by metabolic trapping. Both pyridoxine and
      pyridoxal were found to be metabolised to pyridoxal phosphate in whole cells. The
      majority of pyridoxal taken up appears to remain as pyridoxal (perhaps protein
      bound) the remainder being slowly phosphorylated to pyridoxal phosphate by
      pyridoxal kinase. The majority of pyridoxine taken up was found to be rapidly
      metabolised to pyridoxal. Evidence was also found supporting the hypothesis that
      pyridoxine may be phosphorylated to pyridoxal phosphate and then rapidly
      converted to pyridoxal phosphate.

PMID- 7729475
TI  - Brugia pahangi: the effects of cecropins on microfilariae in vitro and in Aedes
      aegypti.
AB  - Synthetic cecropins, antibacterial peptides from insect haemolymph, have been
      tested for their ability to attenuate the motility of microfilariae of the
      filarial nematode Brugia pahangi in an in vitro assay. Fifty micromolar
      concentrations of these peptides, equivalent to physiological concentrations in
      immune-stimulated insects, cause significant attenuation of motility compared
      with untreated microfilariae. Similar results were obtained with cecropins A and
      B. This is the lowest concentration for which cecropin has been reported to be
      active against eukaryote organisms. Antiserum to the cecropin homologue
      sarcotoxin 1A successfully blocked the observed activity. When the same
      concentration of cecropin B was coinjected with B. pahangi microfilariae into
      adult females of the mosquito, Aedes aegypti, a significant reduction in the
      numbers of developing larvae was observed.

PMID- 7729476
TI  - Trypanosoma congolense: comparative effects of a primary infection on bone marrow
      progenitor cells from N'Dama and Boran cattle.
AB  - Using in vitro clonogenic assays, the changes in haemopoietic progenitor cell
      levels were compared in the bone marrow of three adult trypanotolerant N'Dama
      cattle and three age-matched trypanosusceptible Boran cattle over 17 weeks (119
      days) of a primary Trypanosoma congolense (clone IL 1180) infection. As the
      infection progressed, a clear tendency of the parasitaemia to decrease was seen
      in the N'Damas, while it remained high throughout the infection in the Borans.
      The decline in the colony-forming units-granulocyte macrophage (CFU-GM) between 7
      and 42 days postinfection (dpi) corresponded with the decreased numbers of
      neutrophils and monocytes in the blood observed in both breeds. Thereafter, a
      further significant drop in the CFU-GM levels was observed in the Borans which
      may partially explain the continued decrease in the numbers of neutrophils and
      monocytes in blood. In contrast, a significant peak of CFU-GM above preinfection
      levels was observed in the N'Damas on 49 dpi, which could partially explain the
      subsequent recovery of the numbers of neutrophils and monocytes in blood. When
      compared to the N'Damas, the Borans had a more dramatic drop in the packed cell
      volume (PCV) from 25 dpi onwards, resulting in significantly lower PCV. From 46
      49 dpi onwards, the mean PCV stabilised at significantly lower levels in the
      Borans than in the N'Damas. The mean corpuscular volume (MCV) levels increased in
      both breeds, but at a much faster rate in the Borans. The clonogenic assays
      demonstrated an erythropoietic response, characterised by peaks above pre
      infection levels of both the early and late erythroid progenitor cells
      (respectively, burst-forming units-erythroid, BFU-E, and colony-forming units
      erythroid, CFU-E), occurring between 35 and 70 dpi in both breeds of cattle.
      However, despite a more severe anaemia in the Borans, the magnitude of their
      erythroid response was similar to that of the N'Damas, suggesting that the
      response of the Borans was insufficient to compensate for the greater degree of
      anaemia. Moreover, the mean PCV did not improve in the Borans, indicating the
      ineffectiveness of their erythropoietic response. An increased rate of
      erythrocyte destruction and/or a defective differentiation and maturation of
      erythroid precursors have also been shown to be partially responsible for this
      persistent anaemia. From 98 dpi onwards, despite the persistent low PCV, the MCV
      decreased to preinfection levels and low CFU-E numbers were observed in the
      Borans. Over the same period, in the N'Damas the mean PCV progressively increased
      to reach 25%, which fell within the low normal range for cattle.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7729477
TI  - Plasmodium yoelii: 17-kDa hepatic and erythrocytic stage protein is the target of
      an inhibitory monoclonal antibody.
AB  - Infected hepatocytes are important targets for malaria vaccines. To identify
      Plasmodium yoelii proteins expressed in infected hepatocytes, we immunized BALB/c
      ByJ mice with P. yoelii liver stage schizonts and produced a panel of monoclonal
      antibodies (Mabs). An IgG1 Mab, navy yoelii liver stage 3 (NYLS3), had the
      strongest reactivity against liver stage parasites and was selected for further
      characterization. The Mab does not recognize P. yoelii sporozoites, but
      recognizes liver stage parasites within 6 hr of invasion of mouse hepatocytes and
      throughout the hepatic and asexual erythrocytic stages of the parasite life cycle
      as determined by the immunofluorescent antibody test. This Mab is species
      specific, and it reacts with liver stages of P. yoelii but does not react with
      liver stages of other Plasmodium species. The protein recognized by this Mab is
      present on the parasitophorous vacuole membrane of infected hepatocytes and
      erythrocytes as demonstrated by immunoelectron microscopy and has a relative
      molecular weight of 17 kDa as demonstrated by immunoblot of an extract of
      infected erythrocytes. It is therefore designated P. yoelii hepatic and
      erythrocytic stage protein, 17 kDa or PyHEP17. When added to primary cultures of
      mouse hepatocytes 24 hr after inoculation with P. yoelii sporozoites, when all
      sporozoites have invaded hepatocytes, NYLS3 eliminates up to 98% of liver-stage
      parasites. Intravenous injection of NYLS3 into mice delays the onset and reduces
      the density of blood-stage parasitemia after sporozoite or blood-stage challenge.
      The P. falciparum and P. vivax homologs of PyHEP17 may therefore be important
      targets for vaccines designed to attack the hepatic and erythrocytic stages of
      the parasite life cycle.

PMID- 7729478
TI  - Plasmodium falciparum: alterations in organelle transcript abundance during the
      erythrocytic cycle.
AB  - The malaria parasite Plasmodium falciparum has two extrachromosomal DNAs, a 6 kb
      reiterated element which appears to be the mitochondrial DNA and a 35 kb circular
      DNA of unknown function. Examination of relative steady-state transcript
      abundance during parasite development in the erythrocyte shows that transcripts
      of 6 kb element protein-coding genes are least abundant in the ring and early
      trophozoite stages and most abundant in late trophozoites and schizonts, while
      transcripts from the RNA polymerase subunits of the 35 kb DNA, also least
      abundant in ring stage, are relatively similar in abundance in succeeding stages.
      The fragmented rRNAs of the 6 kb element appear to be constitutively abundant
      except for an increase in the schizont stage, while rRNAs from the 35 kb DNA are
      least abundant in early trophozoites and most abundant in schizonts. Thus the
      relative abundance of organelle transcripts alters during the erythrocytic
      portion of the P. falciparum developmental cycle. These alterations may reflect
      the relative importance of the roles played by organelle gene products in
      different life cycle stages.

PMID- 7729479
TI  - Dictyocaulus viviparus: surface antigens of the L3 cuticle and sheath.
AB  - The bovine lungworm Dictyocaulus viviparus induces a highly protective immune
      response in the bovine host. It is consequently a particularly useful host
      parasite system for the study of those antigens and immune responses which can
      induce protective immunity against a parasitic nematode. We have generated
      monoclonal antibodies to the L3 cuticle and sheath surfaces in order to define
      antigens present at the host-parasite interface of infective larvae. Three
      monoclonal antibodies generated against the surface of the infective L3 cuticle
      bind to a PC-like hapten, and the presence of such an epitope exposed on the
      cuticular surface appears to be unique to the D. viviparus L3. Six monoclonal
      antibodies which bind to the surface of the L3 sheath all detect an antigen which
      is immunodominant in immunised cattle. The possible basis and implications of
      such marked antigenicity of a molecule on the L3 sheath surface are discussed.

PMID- 7729480
TI  - Onchocerca volvulus: parasitologic and serologic responses in experimentally
      infected chimpanzees and mangabey monkeys.
AB  - Six chimpanzees (Pan troglodytes) and six mangabey monkeys (Cercocebus atys) were
      inoculated with Onchocerca volvulus third-stage larvae (L3) of West African
      origin. Two chimpanzees each received 200, 300, or 400 L3, while three mangabeys
      each received either 50 or 250 L3. All six chimpanzees became microfilaria
      positive between 11 and 25 months postinoculation (PI), while two of the six
      mangabeys were skin-snip positive at 24 and 37 months PI, respectively. All
      chimpanzees developed antibodies to two native antigens of 14 and 22 kDa and to
      the recombinant antigens OV16, OC3.6, and OC9.3. Marked antibody responses were
      observed in the mangabey monkeys, and in general, the responses were similar to
      those observed in the chimpanzees. However, in the mangabeys, these responses did
      not generally manifest themselves until later in the infection. The results of
      this study suggest that in chimpanzees, the smallest inoculum used, 200 L3, was
      sufficient to initiate consistent infections that had parasitologic and
      immunologic parameters equivalent to animals inoculated with larger numbers of
      larvae. Similarly, inoculation of mangabey monkeys with small numbers of larvae
      appeared to be as likely to establish infection and induce immunologic responses
      as did inoculation of larger numbers of larvae. Microfilaria-positive chimpanzees
      and mangabey monkeys were examined by three conventional imaging techniques (X
      ray, ultrasound, and magnetic resonance imaging (MRI)), but no adult worms or
      nodules could be identified in any animal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729481
TI  - Plasmodium falciparum: typing of malaria parasites based on polymorphism of a
      novel multigene family.
AB  - Pf60.1, a marker recently isolated from the human malaria parasite Plasmodium
      falciparum, defines a large multigene family encoding antigens of 60 kDa,
      expressed by the blood stages (Carcy et al., Molecular and Biochemical
      Parasitology, 1994, 68, 221-233). Southern blotting showed that DNA from all
      strains and field isolates analyzed contained a large number of Pf60.1 copies.
      Considerable RFLP was observed. This diversity could be likewise visualized by
      analyzing PCR fragments amplified using primers derived from the Pf60.1 insert.
      Specific, multiple-band patterns were generated from laboratory strains, cloned
      lines, or wild isolates. This was further outlined after RsaI digestion of the
      PCR products. The sensitivity of this amplification was such that products could
      be visualized using a DNA amount representing less than one genome equivalent.
      Moreover, amplification was observed in some strains using a single primer,
      suggesting that some members of the Pf60.1 family are adjacent in an inverted
      orientation. This analysis confirmed the genetic similarity of a subset of
      laboratory strains. The results described here show that the extended diversity
      of this P. falciparum gene family provides a useful and sensitive PCR approach
      for strain typing.

PMID- 7729482
TI  - Echinococcus granulosus: interactions with host complement in secondary infection
      in mice.
AB  - Complement has been shown to lyse protoscoleces of Echinococcus granulosus, but
      products from this parasite are able to consume complement, and this has been
      proposed as an evasion mechanism. The murine secondary hydatidosis model, with
      intraperitoneal inoculation, is used in this work to assess the occurrence in
      vivo of complement consumption by the parasite as well as the role of complement
      during the establishment of infection. Although the measurement of systemic
      levels of C3 activation, total C3, and hemolytic complement in challenged mice
      yielded no evidence of complement consumption, the relevance of local consumption
      at the site of infection cannot be ruled out. The role of complement during
      establishment of infection was assessed by comparing parasite burdens in normal
      and complement-depleted mice. Complement depletion by treatment with cobra venom
      factor caused a 79% reduction in cyst numbers (P < 0.05). Possible explanations
      of this unexpected result are discussed. The results presented suggest that lysis
      or opsonization by host complement are not effective against the establishing
      parasite in this model. They also indicate the significance of complement
      activation by the parasite needs to be studied at a local level.

PMID- 7729483
TI  - Plasmodium falciparum: detection of antifolate resistance by mutation-specific
      restriction enzyme digestion.
AB  - We describe here a rapid procedure to predict the resistance of Plasmodium
      falciparum to pyrimethamine or cycloguanil. The method consists of amplification
      by PCR of the DHFR gene followed by restriction enzyme digestion of codons 16 and
      108. Three different enzymes are used to cut the wild-type, 108-threonine mutant,
      and 108-asparagine mutant gene. Since every natural antifolate-resistant isolate
      identified until now carries a mutation in codon 108, determination of the nature
      of this codon can predict the sensitivity of any P. falciparum isolate.

PMID- 7729484
TI  - Trichinella spiralis: cloning and characterisation of two repetitive DNA
      sequences.
AB  - Digestion of genomic DNA of Trichinella spiralis with EcoRI reveals the presence
      of several families of repetitive DNA. Two small repeats of 516 and 604 bp,
      respectively, have been cloned and sequenced. The two repeats are related to each
      other and to a 1.1-kb repetitive DNA. Similar sequences are not detected in other
      species by hybridisation. There are about 270 copies of each small repeat per
      haploid genome and these are organised in large arrays of > or = 50 kb. The basic
      repetitive unit appears to contain one copy of each repeat. This repetitive DNA
      is transcribed in muscle-stage larvae although it is not protein coding.

PMID- 7729486
TI  - Trypanosoma congolense: developmental regulation of protein kinases and tyrosine
      phosphorylation during the life cycle.
AB  - In higher eukaryotes, key steps in the control of growth and proliferation are
      regulated by protein phosphorylation. However, little is known about the role of
      protein phosphorylation in the developmental cycles of pathogenic protozoa. In
      Trypanosoma brucei, only the bloodform and procyclic form stages can be obtained
      in sufficient numbers for biochemical analyses. However, the entire life cycle of
      Trypanosoma congolense can be generated in vitro, providing sufficient material
      for analyses of the different developmental stages. The studies reported here
      provide a series of snapshots documenting the activity of a number of protein
      serine/threonine kinases and the pattern of tyrosine-phosphorylated proteins
      throughout the T. congolense developmental cycle. Metacyclic forms and mammalian
      bloodforms showed similar profiles of protein kinase activity, as did procyclic
      forms and epimastigotes. Most tyrosine-phosphorylated proteins were shared
      between all developmental stages, with the exception of a 100-kDa metacyclic
      specific species. The developmental changes in molecules involved in protein
      phosphorylation in the different developmental stages support the concept that
      changes in protein phosphorylation networks are important correlates of the
      developmental process in African trypanosomes.

PMID- 7729485
TI  - High circulating levels of fibronectin and antibodies against its RGD adhesion
      site during mouse Trypanosoma cruzi infection: relation to survival.
AB  - The levels of fibronectin (FN), a multifunctional glycoprotein known to mediate
      in vitro Trypanosoma cruzi-host cell adhesion, were measured in the plasma of T.
      cruzi-infected BALB/c mice. The infection induced a long-lasting increase of
      fibronectin levels during the acute parasitemic phase of the disease.
      Immunoblotting analysis showed the occurrence of lower-molecular-size FN
      fragments in the plasma of acutely infected animals, suggesting an infection
      related FN degradation. FN levels were found to be significantly lower in dying
      mice harboring higher parasitemias than in surviving animals. A weak level of
      natural IgM against the RGD adhesion site of FN was detected before and during
      the first 3 weeks of infection. The level was significantly higher in surviving
      mice. From the fourth week postinfection, a significant increase in the levels of
      anti-RGD antibodies coincided with a decrease of circulating FN. These antibodies
      were mainly of the IgM, IgG1, and IgG2a isotypes. Taken together, these data
      suggest that both FN and anti-FN antibodies may contribute to the outcome of T.
      cruzi infection in mice.

PMID- 7729487
TI  - Brugia malayi: localisation and differential expression of extracellular and
      cytoplasmic CuZn superoxide dismutases in adults and microfilariae.
AB  - We have determined the levels of superoxide dismutase (SOD) in different stages
      of the lymphatic filarial nematode parasite of man, Brugia malayi. Adult male
      worm extracts showed the highest levels of enzyme activity at 34.5 U mg-1, and
      there was no significant difference in the overall levels of SOD in extracts of
      adult female worms and microfilariae (27.1 and 26.7 U mg-1, respectively). SOD
      activity was detected in the culture medium of parasites maintained in vitro,
      with particularly high levels of specific activity in media in which males and
      females were maintained (357 and 339 U mg-1, respectively), indicative of active
      secretion. In all cases, this was accounted for predominantly by CuZn SOD,
      assessed by potassium cyanide inhibition. Northern blots with cDNA probes
      specific for cytoplasmic and extracellular CuZn SODs indicated that levels of
      mRNA for the cytoplasmic form were similar between adults and microfilariae,
      whereas expression of the extracellular form was 10x higher in adult worms.
      Western blots with an antibody to recombinant CuZn SOD demonstrated that higher
      levels of the extracellular protein were present in adult male worms, whereas the
      cytoplasmic form was present in roughly equivalent amounts in males, females, and
      microfilaria. Iodination and immunoprecipitation experiments indicated that the
      extracellular enzyme was accessible to surface labeling of both male and female
      adult worms, but not microfilaria. Immuno-electron microscopy showed that CuZn
      SOD was localised predominantly in the hypodermis of adult parasites, with an
      asymmetric distribution in the intercordal regions suggestive of
      compartmentalisation into several distinct syncytia. No labeling was evident in
      the cuticle, and thus the accessibility of the extracellular enzyme to extrinsic
      iodination in adult worms remains unclear. No binding of antibody was
      demonstrable in the glandular region of the oesophagus or the uterus of females,
      presumed to be major sites of synthesis for secreted proteins. Dense labeling was
      observed in the seminal fluid surrounding spermatazoa in the vas deferens of male
      parasites. These data also suggest that, as observed in mammals, nematode
      spermatazoa are particularly susceptible to oxidative damage and are protected
      during storage by secreted anti-oxidant enzymes.

PMID- 7729488
TI  - Brugia malayi: differential susceptibility to and metabolism of hydrogen peroxide
      in adults and microfilariae.
AB  - The sensitivity of microfilariae and adult Brugia malayi to hydrogen peroxide
      (H2O2) was determined in vitro, and parasite viability assessed by incorporation
      of 2-deoxy-D-[1-3H]glucose. Both stages were surprisingly resistant to peroxide
      stress. Microfilariae tolerated the direct addition of H2O2 to medium in which
      they were incubated at concentrations up to 50 microM, whereas adult worms
      survived the addition of 100 microM H2O2 and showed slightly impaired viability
      at 150 microM H2O2. Higher concentrations were lethal in both cases. This
      observation of differential susceptibility was reproducible when parasites were
      subjected to continuous generation of H2O2 via glucose/glucose oxidase.
      Microfilariae remained viable over a 4-hr period when challenged with
      concentrations which generated 20 microM H2O2 in the absence of parasites. Adults
      survived higher concentrations of glucose oxidase, which generated 200 microM
      H2O2 over the same time period. Under these conditions the parasites effectively
      countered the rate of peroxide generation by metabolising the product. Protein
      carbonyl formation was detectable at sublethal concentrations of glucose/glucose
      oxidase, but malonaldehyde formation was only detectable coincident with parasite
      death. The rate of H2O2 consumption by parasites was determined and showed that
      adult worms metabolised it at a rate 23x faster than microfilariae, expressed as
      activity per wet weight. Assessment of enzyme activities in parasite extracts
      demonstrated that H2O2 metabolism was effected principally by catalase activity,
      which was elevated in adult worms relative to microfilariae. Cytochrome c
      peroxidase activity was also detected and was roughly equivalent in both stages.
      Glutathione peroxidase and NADH/NADPH-dependent consumption of H2O2 were absent,
      and the rate of nonenzymic reduction of H2O2 coupled to glutathione oxidation did
      not contribute significantly to metabolism. Glutathione reductase activity and
      total glutathione content were equivalent in adults and microfilariae. This study
      illustrates that Brugia malayi are much more resistant to H2O2 than other
      filarial species examined to date and can effectively metabolise levels in excess
      of those potentially generated by activated leucocytes.

PMID- 7729489
TI  - Entamoeba histolytica: induction and isotype analysis of antibody producing cell
      responses in Peyer's patches and spleen after local and systemic immunization in
      male and female mice.
AB  - The purpose of this work was to determine if anti-amebic antibody producing cell
      responses could be elicited in Peyer's patches and spleen in mice locally or
      systemically immunized with glutaraldehyde-fixed trophozoites of Entamoeba
      histolytica (GFT). The animals were inoculated with either a single or four doses
      of GFT via intragastric, rectal, and intraperitoneal routes. The anti-amebic
      antibody producing cell responses were analyzed by a spot forming cell assay
      (ELISPOT). The kinetics of antibody response revealed that a single dose of GFT
      by any route evoked anti-amebic responses in Peyer's patches and spleen.
      Furthermore, antibody producing cells of the three major isotypes were produced
      in both Peyer's patches and spleen of the mice receiving four doses of GFT, by
      either local or systemic routes. Our results indicate that immunization with GFT
      can induce a considerable number of specific antibody producing cells, which seem
      to remain in the Peyer's patches. After rectal and intraperitoneal immunization,
      females produced higher anti-amebic responses than males. Since either local or
      systemic immunization with GFT elicits both mucosal and systemic anti-amebic
      responses, this strategy should be considered as a promising tool for future
      elaboration of an anti-amebic vaccine.

PMID- 7729490
TI  - Acanthocheilonema viteae: reduction in the expression of protective immunity
      against infective larvae in the jird as assessed by micropore chamber vs systemic
      challenge infections.

PMID- 7729491
TI  - Trypanosoma brucei: a preferential splicing at the inverted polyadenylation site
      of the VSG mRNA provides further evidence for coupling between trans-splicing and
      polyadenylation.

PMID- 7729492
TI  - Evidence by in situ hybridization for stage-specific expression of the ATP/ADP
      translocator mRNA in Plasmodium falciparum.

PMID- 7729493
TI  - Trypanosoma cruzi: accumulation of polycistronic hsp70 RNAs during severe heat
      shock.

PMID- 7729494
TI  - The FL-160 genes of Trypanosoma cruzi are dispersed on multiple chromosomes.

PMID- 7729496
TI  - The eosinophil leukocyte: controversies of recruitment and function.
AB  - Eosinophil leukocytes have been studied for over 100 years, with various theories
      being advanced of the mechanism of their recruitment and function, especially in
      relation to the lesions of allergy, asthma and parasitism. Early notions of
      recruitment and function depended on observations of the cells in inflammatory
      lesions, while later theories have used additional information from in vitro
      studies. Many issues are still unresolved. This review aims to cover the older
      and more recent literature of the mechanisms of accumulation of eosinophil
      leukocytes and their functions, with a view to illuminating the controversies and
      difficulties of research in the area.

PMID- 7729495
TI  - Getting there and being there in the cerebral cortex.
AB  - The mammalian neocortex is composed of functional areas that are specified to
      process particular aspects of information. How is this specification achieved
      during development? Since cells migrate to their final positions in the
      developing nervous system, a central issue is the relation between cellular
      migration and positional information. This review combines evidence for early
      positional specification in the developing cortex with evidence for cellular
      dispersion during migration. A model is suggested whereby stable cues provide
      positional information and minorities of 'displaced' cells are respecified
      accordingly. Comparison with other parts of the CNS reveals that cellular
      dispersal is ubiquitous and has to be included in any mechanism relaying
      positional specification. Ontogenetic and phylogenetic considerations suggest
      that radial glial cells might provide the positional information in the
      developing nervous system.

PMID- 7729497
TI  - Characterisation of human skin conductance at acupuncture points.
AB  - Some physicians use the electrical conductance of the skin, particularly at the
      acupuncture points, for diagnostic purposes. This paper deals with the
      quantification of the skin conductance at some acupuncture points under well
      defined conditions using the electrode materials gold, graphite, silver and
      brass. The observed current response appeared to be best described by two
      exponentials.

PMID- 7729498
TI  - Pineal 'synaptic' ribbon numbers and melatonin synthesis of rat are resistant to
      guanethidine sympathectomy.
AB  - Chemical sympathectomy is widely used to study the impact of the noradrenergic
      system on neuronal and neuroendocrine circuits. We tested the effects of
      intraperitoneal injections of guanethidine, an adrenergic neuron blocking agent,
      on selected functional parameters of the rat pineal gland which are known to be
      under sympathetic influence. The reliability of the method was demonstrated by
      the clear enophthalmus developed by experimental animals. However, neither the
      numbers of 'synaptic' ribbons nor melatonin synthesis differed between treated
      and control rats, both parameters exhibiting the nocturnal increase seen in
      intact animals. These results are in striking contrast to those obtained upon
      chemical sympathectomy with 6-hydroxydopamine or surgical superior cervical
      ganglionectomy. We conclude that guanethidine is not capable of sufficiently
      removing noradrenergic influence from the rat pineal gland, and that this
      substance is thus inferior to other experimental methods of sympathectomy.

PMID- 7729499
TI  - Estradiol-induced changes in TSH-like immunoreactivity of pituitary cells in
      female rats.
AB  - Beta-thyrotropin (TSH)-producing cells in the pituitary pars distalis of female
      rats were studied using rabbit anti-rat beta-thyrotropin (TSH) serum and a
      peroxidase-antiperoxidase (PAP) immunohistochemical procedure. Animals were
      neonatally treated with 1 mg estradiol-dipropionate (EDP) and sacrificed at
      different stages of development up to adulthood. Intact females of the
      corresponding age served as the controls. Morphometry and stereology were used to
      evaluate the changes in TSH-cell number and volume densities of the cells and
      nuclei. All morphometric parameters examined in estradiol-treated animals showed
      a significant decrease in comparison with immunoreactive TSH cells of age-matched
      controls. The most prominent EDP-induced changes were evident in peripubertal 38
      day-old rats, the number and volumetric densities of both TSH cells and their
      nuclei being reduced by about 90% compared to intact pituitary. This decrease in
      the number and volume densities of TSH cells in EDP-treated rats explicitly
      demonstrated that this hormone, applied neonatally, has an inhibitory effect on
      TSH-immunoreactive cells up to adulthood, in accordance with our earlier data
      obtained by light and electron microscopy.

PMID- 7729500
TI  - Complex formation between gamma-immunoglobulin and calmodulin in calcium-free
      conditions.
AB  - We show that gamma-immunoglobulin (IgG) binds calmodulin (CaM) in a Ca(2+)
      independent manner, with Kd value of (1.7 +/- 0.5) x 10(-7) M. A single IgG
      molecule maximally bound 10 CaM molecules. The binding is to the heavy chain or
      Fab portion, but not the Fc portion, of the IgG molecules. Ca2+ greatly
      diminished the interaction between IgG and CaM, with IC50 = 8-9 microM. These
      data give a novel insight into protein-protein interactions.

PMID- 7729501
TI  - Suppression of natural killer cell activity in mouse spleen lymphocytes by
      several dopamine receptor antagonists.
AB  - The effects of dopaminergic receptor inhibitors such as thiothixine (D1/D2),
      fluphenazine (D1/D2), trifluoperazine (D1/D2), pimozide (D2), flupenthixol
      (D1/D2), (+/-)-SKF 83566 (D1), and spiperone (D2) on splenic natural killer (NK)
      cell cytotoxic activities were assessed in vitro using mouse spleen lymphocytes
      or enriched NK cells. Both the activities of the splenic NK cell cytotoxicity and
      the effector-target cell conjugation were suppressed by thiothixine,
      fluphenazine, and trifluoperazine at concentrations from 2.64 to 14.78 microM. In
      addition, the augmentation of the cytolytic activity of NK cells induced by
      interferon-alpha or interleukin-2 was antagonized by pretreatment with these
      neuroleptic compounds. However, neither the splenic NK cell cytotoxicity nor the
      effector-target cell conjugation were affected by treatment with other
      neuroleptic compounds such as pimozide, flupenthixol, (+/-)-SKF 83566, and
      spiperone. Thus, it appears that neuroleptic compounds such as thiothixine,
      fluphenazine, and trifluoperazine may act through the mechanisms other than a
      dopaminergic pathway to affect the NK cell-target cell interaction.

PMID- 7729502
TI  - Hepatic hydroxylation of melatonin in the rat is induced by phenobarbital and
      7,12-dimethylbenz[a]anthracene--implications for cancer etiology.
AB  - The protective function of the pineal hormone melatonin in the etiology of cancer
      and carcinogenic activation is increasingly well-established. Low melatonin
      levels seem to parallel cancer growth. The question arises as to which factors
      cause the depression of melatonin levels and what the direct effects are.
      Melatonin is known to be metabolized in the liver by hydroxylation and subsequent
      conjugation yielding 6-sulfatoxymelatonin as a main product. Nevertheless, the
      microsomal monoxygenases catalyzing the first step have been poorly investigated.
      To further characterize these enzymes, typical inducers of three different sub
      classes, namely phenobarbital, 7,12-dimethylbenz[a]anthracene, and 17 beta
      estradiol, were administered to female Fischer rats. Circadian urinary excretion
      patterns of melatonin and 6-sulfatoxymelatonin were determined over a 24-hour
      period on the third (second) day of induction. Liver homogenates were used to
      monitor the in vitro conversion of melatonin or 6-hydroxymelatonin to 6
      sulfatoxymelatonin. Results of both approaches showed the microsomal
      monoxygenases catalyzing the 6-hydroxylation of melatonin to be strongly
      inducible by phenobarbital and to a lesser degree by the polyaromatic hydrocarbon
      7,12-dimethylbenz[a]anthracene. The dramatic depletion of circulating melatonin
      as a result of these induction patterns and its possible implications for
      oncogenesis are discussed.

PMID- 7729503
TI  - A2 adenosine receptors in human glomerular mesangial cells.
AB  - A2 adenosine receptors were characterized in human glomerular mesangial cells
      using [3H]5'-N-ethylcarboxamidoadenosine (NECA) as a tracer. There was a single
      group of receptor sites with a KD of 184 nM, and a number of sites of 317 fmol/mg
      of cell protein. Adenosine agonists increased 5'-nucleotidase activity via A2
      receptor stimulation. The specific A2 agonist-NECA, at 0.1 and 1 micron, was a
      potent inhibitor of DNA synthesis.

PMID- 7729504
TI  - (E)-3-tridecen-2-one, an antibiotic from the interdigital glands of black-tailed
      deer Odocoileus hemionus columbianus.
AB  - (E)-3-tridecen-2-one, the major volatile component of interdigital gland extracts
      from the black-tailed deer, Odocoileus hemionus columbianus, inhibited the growth
      of gram-positive bacteria and fungi. The bacteria, Propionibacterium acnes, and
      the fungi, Trichophyton mentagrophytes had a minimum inhibitory concentration
      (MIC) of 12.5 micrograms/mL and 25 micrograms/mL, respectively.

PMID- 7729505
TI  - In vitro development of rat embryos obtained from diabetic mothers.
AB  - Rat embryos of 9.5 or 10 days of gestation were removed from control or
      streptozotocin-diabetic mothers and cultured in normal rat serum (180 mg%
      glucose) or in diabetic serum (600 mg% glucose). The development of control
      embryos in normal serum was adequate. Embryos from normal mothers cultured in
      diabetic serum showed signs of developmental retardation. The development of
      embryos obtained from diabetic mothers was severely impaired, regardless of the
      gestational age or the culture medium. These results suggest that a diabetic
      maternal milieu produces irreversible effects in the embryo very early in
      gestation.

PMID- 7729506
TI  - Body size variability and water balance: a comparison between mainland and island
      populations of Mastomys huberti (Rodentia: Muridae) in Senegal.
AB  - Generally rodents are found to be larger on islands than on the mainland.
      However, there are some exceptions to this rule, and the aim of this paper is to
      examine one of them. On the mainland of Senegal, Mastomys huberti occupies humid
      habitats. However, it occurs also on dry and sandy islands (Saloum delta), where
      its representatives are dwarf. Since water availability appeared to be the
      limiting factor in these islands when compared to the mainland, we studied water
      turnover characteristics in relation to body size, in mainland and island
      populations at the end of the dry season, under both field and laboratory
      conditions. All populations were found to be water balanced in their natural
      habitats. They presented similar rates of water turnover, even though island
      animals were subjected to stronger constraints than mainland ones. Laboratory
      experiments suggested that the physiological plasticity of one of the island
      populations may be reduced. Island populations have a higher kidney size to body
      weight ratio than those from the mainland. We propose that smaller size in the
      islands allows the maintenance of water balance with a smaller amount of water,
      and that a higher ratio of kidney filtration surface to body size may help
      Mastomys huberti to survive in dry islands. We discuss the factors responsible
      for body size variability and variation in water exchange characteristics and
      conclude that different factors could explain body size variation among island
      populations, depending on the species considered and the ecological constraints
      met within the islands.

PMID- 7729507
TI  - Individual recognition and incest avoidance in eusocial common mole-rats rather
      than reproductive suppression by parents.
AB  - Non-reproductive females in families of eusocial common mole-rats (Cryptomys sp.,
      Rodentia) are not suppressed by their mother, (either behaviourally or
      pheromonally) as is generally assumed. They do not mate with their father and
      brothers simply because they are not sexually attractive for them (and vice
      versa). The incest avoidance is based on the capability to recognize (and keep in
      memory for up to three weeks) each family member individually. A 'sterile'
      daughter may conceive and deliver young in her parental family if given the
      opportunity to mate with an unfamiliar mate in a separate cage. In this way, two
      females may breed side by side in one family.

PMID- 7729508
TI  - An estimation of minimal genome size required for life.
AB  - The number of indispensable chromosomal loci for a bacterium, Bacillus subtilis
      was estimated. Seventy-nine randomly selected chromosomal loci were investigated
      by mutagenesis. Mutation at only six loci rendered B. subtilis unable to form
      colonies. In contrast, mutants for the rest of the 73 loci retained the ability
      to form colonies. Mutant B. subtilis with multiple-fold mutations of those
      dispensable loci (7-, 12- or 33-fold) were not impaired in their ability to form
      colonies on nutritionally adequate medium, indicating that up to 33 dispensable
      loci were simultaneously abolished. Given the statistical analyses for the
      frequency of indispensable loci (6 out of 79), total indispensable genetic
      material would be included within about 562 kbp. The hypothetical minimum genome
      size lies in the range of those currently determined smallest genomes for
      bacteria.

PMID- 7729509
TI  - Pulmonary surfactant-associated polypeptide SP-C in lipid micelles: CD studies of
      intact SP-C and NMR secondary structure determination of depalmitoyl-SP-C(1-17).
AB  - The surfactant-associated polypeptide C (SP-C) is a 35-residue lipopolypeptide
      which is essential for the function of surfactants used for therapy of infant
      respiratory distress. Modeling based on the recently determined nuclear magnetic
      resonance (NMR) structure of native SP-C in an organic solvent showed that SP-C
      could readily insert into fluid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
      bilayers. The present paper describes further physical-chemical studies of intact
      SP-C and its N-terminal 17-residue polypeptide fragment, depalmitoyl-SP-C(1-17),
      in the presence of dodecylphosphocholine micelles. The results obtained provide a
      link between the NMR solution structure and the behaviour of SP-C in an ordered
      lipid environment, and thus present new insights for rational design of SP-C
      analogs for therapeutic purposes.

PMID- 7729510
TI  - Limited proteolysis of cytochrome c in trifluoroethanol.
AB  - Horse heart cytochrome c is cleaved by thermolysin in 50% aqueous TFE (v/v) at
      neutral pH (25 degrees C, 24 h) at the Gly56-Ile57 peptide bond of the 104
      residue chain of the protein. Additional, but anyway minor, fragmentation at the
      Gly45-Phe46 and Met80-Ile81 peptide bonds is also observed. On the other hand, in
      buffer only and in the absence of TFE, cytochrome c is digested by thermolysin to
      numerous small peptides. Considering the broad substrate specificity of the TFE
      resistant thermolysin, clearly the conformational state of the protein substrate
      dictates the observed selective proteolysis. It is proposed that the highly
      helical secondary structure acquired by cytochrome c when dissolved in aqueous
      TFE hampers binding and adaptation of the protein substrate at the active site of
      the protease and that peptide bond fission occurs at flexible chain segments
      characterized by a low alpha-helix propensity.

PMID- 7729511
TI  - Does phosphorylase kinase control glycogen biosynthesis in skeletal muscle?
AB  - Immunoblotting as well as enzyme assays demonstrate the presence of the self
      glucosylating protein, glycogenin, in the protein-glycogen complex, in the
      sarcoplasmic reticulum and in phosphorylase kinase. In all three compartments
      glycogenin occurs in different, albeit, defined glucosylated forms, which upon
      deglucosylation are converted into a 42 kDa form. We suggest that phosphorylase
      kinase might have a dual function in glycogen biogenesis: firstly, control of
      glycogen degradation in the protein-glycogen complex via phosphorylation of
      glycogen phosphorylase b; secondly, regulation of glycogen biosynthesis on the
      sarcoplasmic reticular membranes via phosphorylation and thereby inhibition of
      glycogen synthase.

PMID- 7729512
TI  - Processing of proendothelin-1 by human furin convertase.
AB  - Endothelin-1 (ET-1) is the most potent vasoactive peptide known to date. The
      peptide is initially synthesized as an inactive precursor (proET-1) which
      undergoes proteolysis at specific pairs of basic amino acids to yield bigET-1.
      Production of ET-1 then proceeds by cleavage of bigET-1 by the endothelin
      converting enzyme (ECE). Here, we demonstrate that the in vitro cleavage of proET
      1 by furin, a mammalian convertase involved in precursor processing, produced
      bigET-1. Upon further processing, bigET-1 was converted to biologically active ET
      1. Furthermore, we demonstrate that the furin inhibitor, decanoyl-Arg-Val-Lys-Arg
      chloromethylketone, abolished production of ET-1 in endothelial cells.

PMID- 7729513
TI  - Beta-glucosidase, beta-galactosidase, family A cellulases, family F xylanases and
      two barley glycanases form a superfamily of enzymes with 8-fold beta/alpha
      architecture and with two conserved glutamates near the carboxy-terminal ends of
      beta-strands four and seven.
AB  - Comparison of the recently determined crystal structures Pseudomonas fluorescens
      subsp. cellulosa family F xylanase, (1-3)-beta-glucanase and (1-3,1-4)-beta
      glucanase and the catalytic domain of E. coli beta-galactosidase reveals that
      they belong to a superfamily of 8-fold beta/alpha-barrels with similar amino acid
      residues at their active sites. In the three families that these enzymes
      represent, the nucleophile is a glutamate, which is located close to the carboxy
      terminus of beta-strand seven. In addition all three enzymes have the sequence
      asparagine-glutamate close to the carboxy-terminus of beta-strand four. This
      glutamate has been identified as the acid/base in the family F xylanases and is
      essential for catalysis in beta-galactosidase. We suggest that the equivalent
      residue in the barley glucanases is the acid/base. Analysis of the sequences of
      family 1 beta-glucosidases and family 5 cellulases shows that these enzymes also
      belong to this superfamily which we call the 4/7 superfamily.

PMID- 7729514
TI  - The small G-protein ARF1GDP binds to the Gt beta gamma subunit of transducin, but
      not to Gt alpha GDP-Gt beta gamma.
AB  - AlF4- activates heterotrimeric G-proteins G alpha subunits but not small GDP/GTP
      binding proteins like ARF1. On retinal membranes containing holotransducin (Gt
      alpha GDP-Gt beta gamma) and incubated with ARFGDP, AlF4- induced Gt alpha GDP
      AlF4 release and ARFGDP binding, probably to the remaining membrane-attached Gt
      beta gamma. On phospholipid vesicles reconstituted with Gt beta gamma, ARFGDP
      bound in proportion to Gt beta gamma, and was released upon subsequent Gt alpha
      GDP addition. Thus ARFGDP competes with Gt alpha GDP for binding to Gt beta
      gamma, probably through a conserved motif in the 'alpha 2 helix' of Gt alpha and
      ARF. This motif is found in the C-terminal helix of PH domains that bind to G
      beta gamma.

PMID- 7729515
TI  - Ala335 is essential for high-affinity cAMP-binding of both sites A and B of cAMP
      dependent protein kinase type I.
AB  - A single amino acid substitution (Ala335Asp) in cAMP binding site B of the
      regulatory subunit of cAMP-dependent protein kinase type I was sufficient to
      abolish high affinity cAMP binding for both cAMP binding sites A and B.
      Furthermore, the Ala335Asp mutation increased the activation constant for cAMP of
      the mutant holoenzyme 30-fold and also enhanced the rate of holoenzyme formation.
      Thus, the substitution was responsible for the dominant negative phenotype of the
      enzyme. Activation of mutant holoenzyme with site-selective cAMP analogs
      indicated that the enzyme dissociated through binding to site A only. Our results
      provide evidence that Ala335 is an essential residue for high affinity cAMP
      binding of both sites as well as for the functional integrity of the enzyme.

PMID- 7729516
TI  - Effects of TGF-beta 1 (transforming growth factor-beta 1) on the cell cycle
      regulation of human breast adenocarcinoma (MCF-7) cells.
AB  - The antiproliferative effects of TGF-beta 1 were investigated in a human breast
      adenocarcinoma cell line (MCF-7). We report that TGF-beta 1 inhibits
      proliferation through cell cycle arrest in G1. A MCF-7 cell subline (MCF-7(-)),
      in which the type II TGF-beta receptor is not detected, was shown to be resistant
      to TGF-beta 1 growth inhibitory effect. Cdk2 kinase activity was inhibited in the
      MCF-7 sensitive cell subline in parallel with the inhibition of cell cycle
      progression. In both sensitive and resistant cell lines, TGF-beta 1 treatment did
      not affect cdk2, cdk4, cyclin E and cyclin D1 mRNA and protein levels. However,
      in the MCF-7 sensitive cell subline, a time-dependent increase in cells positive
      for p21WAF1/CIP1 nuclear localization was observed after TGF-beta 1 treatment.
      These findings suggest that TGF-beta 1 inhibition of MCF-7 cell proliferation is
      achieved through a type II receptor-dependent down-regulation of Cdk2 kinase
      activity without modification of Cdk and cyclin expression, but correlated with
      an increase in p21WAF1/CIP1 nuclear accumulation.

PMID- 7729517
TI  - Genomic sequencing reveals absence of DNA methylation in the major late promoter
      of adenovirus type 2 DNA in the virion and in productively infected cells.
AB  - By using methylation-sensitive restriction endonucleases, we have previously
      provided evidence that adenovirus type 2 (Ad2) virion DNA or free intranuclear
      Ad2 DNA in productively infected hamster or human cells is not methylated. We
      have now chosen a different experimental approach and have investigated the major
      late promoter (MLP) sequence of Ad2 DNA for the presence of 5-methyldeoxycytidine
      (5-mC) residues with the genomic sequencing technique. This study has been
      prompted by the finding that the MLP of Ad2 DNA can be inactivated by sequence
      specific methylation in experiments in which a MLP-chloramphenicol
      acetyltransferase construct has been transcribed in a cell-free system from HeLa
      cell nuclear extracts. Virion Ad2 DNA and Ad2 DNA isolated from productively
      infected human or hamster cells between 1 and 48 h post-infection (p.i.) have now
      been analyzed. There is no evidence for the presence of 5-mC in the cytidine
      positions in the MLP of any of these Ad2 preparations. We conclude that DNA
      methylation does not seem to play a role in the early-late control of this viral
      promoter. The sensitivity of the genomic sequencing technique does not permit us
      to exclude the unlikely presence of 5-mC in a few Ad2 DNA molecules.

PMID- 7729518
TI  - Novel avidin and streptavidin binding sequences found in synthetic peptide
      libraries.
AB  - Synthetic resin-bound peptide libraries made of protein L-amino acids have been
      synthesized. During screening of the libraries, peptides that bind to avidin have
      been identified containing a novel motif with two histidines separated by one
      residue. A sub-library was synthesized and screened, and new critical residues
      appeared surrounding the two histidines. Additionally peptide libraries made of D
      amino acids have been screened with avidin and streptavidin and novel motifs have
      been found.

PMID- 7729519
TI  - Temporary loss of glucocorticoid receptor-mediated regulation of gene expression
      in heat-shocked cells.
AB  - The effect of heat shock on the transcriptional activity of glucocorticoid
      receptor was assessed using HeLa cells stably transfected with the
      chloramphenicol acetyltransferase (CAT) gene the transcription of which is
      controlled by two glucocorticoid-responsive elements placed directly upstream of
      a core promoter. Heat shock inactivated the high-affinity glucocorticoid binding
      capacity of the cells and nullified the rate of accumulation of CAT mRNA in the
      presence of hormone. Hormonal responsiveness was restored on return to normal
      temperature concomitantly with recovery of high-affinity glucocorticoid binding
      capacity. Heat inactivation of the receptor was coincident with loss of its
      solubility and apparently unrelated to receptor degradation.

PMID- 7729520
TI  - Inositol(1,3,4,5) tetrakisphosphate plays an important role in calcium
      mobilization from Entamoeba histolytica.
AB  - Calcium release from internal stores of Entamoeba histolytica, a parasitic
      protozoan, was observed by measuring fluorescence of Fura-2. Emptying of
      inositol(1,4,5)trisphosphate (Ins(1,4,5)P3)-sensitive calcium pools in
      permeabilized E. histolytica did not significantly affect subsequent calcium
      release by inositol(1,3,4,5)tetrakis-phosphate (Ins(1,3,4,5)P4). Similarly, prior
      depletion of Ins(1,3,4,5)P4-sensitive stores did not have any influence on
      subsequent calcium release by Ins(1,4,5)P3. The EC50 for calcium release was 0.15
      microM with Ins(1,4,5)P3 and 0.68 microM with Ins(1,3,4,5)P4. In conclusion, the
      Ins(1,3,4,5)P4-sensitive calcium store in E. histolytica is separate and
      independent from the Ins(1,4,5)P3-sensitive pool.

PMID- 7729521
TI  - Characterization of a highly toxic, large molecular size heat-stable enterotoxin
      produced by a clinical isolate of Yersinia enterocolitica.
AB  - A novel heat-stable enterotoxin (ST) designated as Y-STc was purified to
      homogeneity from the culture supernatant of a pathogenic strain of Yersinia
      enterocolitica serotype O3 and its amino acid sequence was determined. The mature
      Y-STc was found to consist of 53 amino acid residues, which includes the putative
      pro-sequence. The molecular weight of Y-STc was 5638 and constituted the largest
      molecular size in the family of currently known STs. The minimum effective dose
      of purified Y-STc in the suckling mouse assay was 0.6 ng (0.0 pmol), indicating
      that, despite the long sequence, Y-STc is the most toxic in the ST family.

PMID- 7729522
TI  - Human CuZn superoxide dismutase enzymatic activity in cells is regulated by the
      length of the mRNA.
AB  - Single functional human CuZnSOD gene encodes two species of mRNA differing in
      size by 200 nucleotides in the 3'-untranslated region (UTR). We studied the
      expression of the CuZnSOD cDNA with different 3'- and 5'-UTR. Deletion in the 5'
      end does not affect the expression of the enzyme, however, deletion in the 3'-UTR
      decreases the level of expression of CuZnSOD. The plasmids containing the long
      CuZnSOD cDNA with all polyadenylation signal sequences utilize primarily the last
      polyadenylation site and give a long mRNA, which produces three times more enzyme
      than the short mRNA lacking the last polyadenylation site and the AU-rich region.

PMID- 7729523
TI  - An amphipathic helical motif common to tumourolytic polypeptide NK-lysin and
      pulmonary surfactant polypeptide SP-B.
AB  - The tumour-lysing and antimicrobial polypeptide NK-lysin and the pulmonary
      surfactant-associated polypeptide SP-B exhibit 24% residue identities (49%
      similarities), including six half-cystine residues in the same disulphide bonding
      pattern, and similar far-UV circular dichroism spectra corresponding to 45-55%
      alpha-helix and 20-25% beta-sheet structures. From this, we conclude that the
      conformations of NK-lysin and SP-B are similar. In contrast, the functional
      properties of the two proteins are dissimilar: SP-B does not exhibit
      antibacterial activity and NK-lysin does not significantly effect phospholipid
      spreading at an air/water interface. Saposins, which solubilize lipids and
      activate lysosomal hydrolases, the pore-forming amoebapores, and parts of acid
      sphingomyelinase and acyloxyacylhydrolase, also share 18-27% sequence identities
      with NK-lysin (and SP-B), including the six conserved half-cystine residues. The
      inclusion of NK-lysin extends the family of saposin-like polypeptides, all
      members of which appear to interact with lipids. Strictly conserved structural
      features with implications for helix topology and lipid interactions are
      observed.

PMID- 7729524
TI  - Assignment of the backbone 1H,15N,13C NMR resonances and secondary structure of a
      double-stranded RNA binding domain from the Drosophila protein staufen.
AB  - NMR spectroscopy has been used to determine the secondary structure of one of the
      double-stranded RNA binding domains from the Drosophila protein staufen. The
      domain has an alpha beta beta beta alpha arrangement of secondary structure, with
      the beta strands forming an antiparallel beta sheet. The secondary structure
      differs from that found in the RNP RNA binding domain.

PMID- 7729525
TI  - Mitochondrial DNA rearrangements: intracellular information system.
AB  - The extent of mtDNA rearrangements has been analyzed in nDNA preparations of rat
      and human with a statistically representative group of oligonucleotides directed
      to two regions of mtDNA: genes for cytochrome oxidase subunits I and III. Human
      PCR preparations generated with oligonucleotides directed 'normally' showed the
      expected fragment for mtDNA and the presence of a plethora of fragments with
      rearrangements (deletions and insertions), in contrast to rat PCR preparations
      under the same reaction conditions in which these kinds of rearranged fragments
      were rarely observed. Both human and rat PCR preparations generated with
      oligonucleotides directed 'inversely' showed numerous fragments, some of which
      showed differences in copy number correlating with distinct phases during
      development/aging. Sequence analysis of some normal and rearranged fragments
      demonstrated in all cases DNA sequences 99% homologous with other mtDNA sequences
      at rearranged fragments. No evidence of nuclear DNA sequences was found. The
      following scheme is proposed for mtDNA rearrangements during the lifetime of an
      organism: variation in copy number of some fragments with inversions of mtDNA
      depends on the specific developmental/aging period; in old cells there is an
      increase in higher molecular weight mtDNA deletions. These findings strongly
      suggest that the mtDNA rearrangements play a role as an intracellular
      'information system'.

PMID- 7729526
TI  - Cloning and expression in Escherichia coli of a cDNA encoding a developmentally
      regulated Ca(2+)-binding protein from Dictyostelium discoideum.
AB  - We have cloned a full-length cDNA from Dictyostelium discoideum which encodes a
      new Ca(2+)-binding protein. The deduced protein (termed CBP1) is composed of 156
      amino acids and contains four consensus metal-ligating loop sequences found in
      helix-loop-helix motifs of many Ca(2+)-binding proteins. When expressed in
      bacteria as a GST fusion protein, CBP1 binds Ca2+ in a 45Ca2+ overlay assay. CBP1
      exhibits little amino acid sequence homology with Dictyostelium calmodulin or
      calfumirin-1 (CAF-1) except in the putative Ca(2+)-binding regions. Moreover,
      unlike calmodulin and CAF-1 expression, CBP1 mRNA is expressed preferentially
      during the multicellular stages of development.

PMID- 7729527
TI  - A new member of the cytosolic O-acetylserine(thiol)lyase gene family in
      Arabidopsis thaliana.
AB  - A cDNA, Atcys-3A, encoding O-acetylserine-(thiol)lyase has been isolated from
      Arabidopsis thaliana. The deduced peptide sequence showed a high level of
      similarity with the bacterial counterpart, and a remarkable percentage of
      identity with other higher plant O-acetylserine(thiol)lyase genes. Sequence
      comparison and Southern blot analysis suggested that Atcys-3A was a new and
      different to the previously reported member of the cytosolic gene family in
      Arabidopsis. The Atcys-3A expression was activated by sulfur limitation,
      requiring a carbon and nitrogen source for maximal expression. A similar pattern
      of regulation was observed at the O-acetylserine(thiol)lyase activity level.
      Northern blot analysis also showed an organ-specific expression of Atcys-3A.

PMID- 7729528
TI  - p56lck plays a key role in transducing apoptotic signals in T cells.
AB  - The CD4 receptor synergizes with the T-cell antigen receptor (TCR) in helper T
      cell activation. However CD4 cross-linking in the absence of simultaneous TCR
      engagement leaves the cells primed to activation dependent apoptosis. To assess
      the role of the CD4 associated protein tyrosine kinase p56lck in CD4 priming to
      apoptosis we have constructed Jurkat T-cell lines stably transfected with a
      constitutively active form of p56lck. These cells were constitutively primed to
      undergo apoptosis upon TCR crosslinking with specific antibodies. In addition the
      Jurkat JCaM1 line, which is defective for p56lck expression, was resistant to TCR
      induced apoptosis. These data indicate that p56lck is required for T-cell
      apoptosis and that CD4 priming of T-cells for antigen dependent apoptosis is due
      to inappropriate or partial activation of the p56lck signal transduction pathway.

PMID- 7729529
TI  - The transcriptional regulation of human arachidonate 12-lipoxygenase gene by NF
      kappa B/Rel.
AB  - As examined by the luciferase assay, a negative regulatory region including the
      NF kappa B motif was found in the 5'-flanking region of the 12-lipoxygenase gene
      in human erythroleukemia cells. The negative control was abolished by a site
      specific mutation of the NF kappa B motif. Probes including the NF kappa B region
      gave positive bands upon a gel-shift assay. The bands were super-shifted by
      antibodies for NF kappa B p50, NF kappa B p65 and c-Rel, and were lost by a NF
      kappa B competitor DNA. Furthermore, the NF kappa B sequence was protected in
      DNase I footprinting. Thus, two kinds of heterodimer (p50 and p65; p50 and c-Rel)
      seemed to control the over-expression of the human 12-lipoxygenase gene.

PMID- 7729530
TI  - Dissection of the dual function of the beta-subunit of protein kinase CK2
      ('casein kinase-2'): a synthetic peptide reproducing the carboxyl-terminal domain
      mimicks the positive but not the negative effects of the whole protein.
AB  - The dual function of the regulatory beta-subunit of protein kinase CK2 is
      highlighted by its ability to abolish calmodulin phosphorylation in contrast to
      its stimulatory effect on the phosphorylation of peptide substrates. Here we show
      that a synthetic peptide reproducing the C-terminal region of the beta-subunit
      (beta[170-215]) stimulates to a similar extent the phosphorylation of either the
      peptide substrate or calmodulin and also protects the catalytic alpha-subunit
      against thermal inactivation as efficiently as full-length beta-subunit. These
      data show that the positive and negative functions of the beta-subunit reside in
      physically separated domains and that the elements responsible for positive
      regulation are located in the C-terminal region.

PMID- 7729531
TI  - Crystallization and preliminary X-ray analysis of a PNA-DNA complex.
AB  - Peptide nucleic acids (PNAs) are DNA mimics with a peptide backbone. PNAs are
      being intensely investigated owing to a potential as gene-targeted drugs. A PNA
      (H-GTAGATCACT-NH2)-DNA (5'-AGTGATCTAC-3') complex has been crystallized in a
      tetragonal space group P4(1)22 with cell dimensions a = b = 79.8, c = 99.9
      angstrum. The crystals diffract to about 5 angstrum resolution.

PMID- 7729532
TI  - Does the folding type of a protein depend on its amino acid composition?
AB  - Proteins of known structures are generally classified into one of the following
      four folding types: alpha, beta, alpha + beta, and alpha/beta proteins. Recent
      findings [Muskal and Kim (1992) J. Mol. Biol. 225, 713-727] suggested that the
      folding type of a protein might basically depend on its amino acid composition.
      If this is true, why is that the predicted results of the protein folding type
      from amino acid composition always failed to reach the desired accuracy? An
      examination of the prediction approach indicates that none of the previous
      algorithms has ever taken into account the coupling effect among different amino
      acid components. In view of this, a new algorithm has been developed which
      distinguishes itself from the previous ones by incorporating such a coupling
      effect. The very high rates, 99.2% and 95.3%, of correct predictions thus
      obtained for a recently constructed training set of 120 proteins and testing set
      of 64 proteins, respectively, provide confirmation of the above suggestion.

PMID- 7729533
TI  - Nuclear recruitment of A1p145 subunit of replication factor C in the early G1
      phase of the cell cycle in Faza 567 hepatoma cell line and hepatocyte primary
      cultures.
AB  - Using a combination of immunoprecipitation and Western blotting with Faza 567
      hepatoma cell extracts revealed that the large subunit of replication factor C
      (A1p145; mRFC140) was in a complex with proliferating cell nuclear antigen
      (PCNA). Western blotting showed that A1p145 was more abundant in nuclear extracts
      from butyrate-treated hepatoma cells which blocks the cells in the G1 phase of
      the cell cycle than from routinely cultured cells. Indirect immunoperoxidase
      analysis of G1 blocked Faza hepatoma cells localized A1p145 protein predominantly
      in the nucleoli. When hepatoma cells were stimulated to progress toward the S
      phase, A1p145 protein was then observed in both the cytoplasm and the nucleoplasm
      of these cells. Studies with early cultured normal hepatocytes which are
      progressing from G0 towards G1, also showed a nucleolus distribution for A1p145.
      This is the first demonstration in mammalian cells that the large subunit of
      replication factor C is associated with PCNA in the nucleus and that its
      distribution within cells changes during the cell cycle.

PMID- 7729534
TI  - 15-cis-beta-carotene found in the reaction center of spinach photosystem II.
AB  - Solvent extraction at approximately 4 degrees C in complete darkness, and
      subsequent analysis by high-pressure liquid chromatography (at approximately 4
      degrees C) using an apparatus equipped with a two-dimensional diode-array
      detector, spectroscopically identified 15-cis-beta-carotene in the reaction
      center (RC) of spinach photosystem II (PS II). The result revises a previous
      conclusion that beta-carotene bound to the PS II RC takes the all-trans
      configuration [Fujiwara, H., Hayashi, H., Tasumi, M., Kanaji, M., Koyama, Y. and
      Satoh, K. (1987) Chem. Lett. 2005-2008], and generalizes the concept established
      for purple photosynthetic bacteria that 15-cis-carotenoid is naturally selected
      by the photosynthetic reaction centers.

PMID- 7729535
TI  - Up-regulation of ICAM-1 expression on human dermal fibroblasts by IFN-beta in the
      presence of TNF-alpha.
AB  - Unstimulated human fibroblasts show low or undetectable ICAM-1 expression.
      Interferon-beta (IFN-beta) at concentrations of 10, 100, and 1000 IU/ml in the
      presence of tumor necrosis factor-alpha (TNF-alpha) significantly increased the
      ICAM-1 expression of fibroblasts in a dose-dependent manner. Treatment with IFN
      beta alone, however, did not up-regulate the ICAM-1 expression. Furthermore the
      attachment of peripheral blood mononuclear cells (PBMCs) to cytokine-treated
      fibroblasts was increased. This augmented attachment was partly inhibited by anti
      ICAM-1 antibody. These results suggest that IFN-beta and TNF-alpha may
      cooperatively modulate the attachment of PBMCs in the dermis.

PMID- 7729536
TI  - Oligomerization state in solution of the cell cycle regulators p13suc1 from the
      fission yeast and p9cksphy from the myxomycete Physarum, two members of the cks
      family.
AB  - The cks proteins (for cdc2 kinase subunit) are essential cell cycle regulators.
      They interact strongly with the mitotic cdc2 kinase, but the mechanism and the
      biological function of this association still await understanding. The
      oligomerization state in solution of two members of this ubiquitous protein
      family, the suc1 gene product from the fission yeast and the newly cloned cksphy
      gene product from the myxomycete Physarum, was investigated by small-angle X-ray
      scattering (SAXS) and biochemical methods. We found that the major molecular
      species are monodispersed monomeric proteins. Minor amounts of dimeric suc1
      proteins were also found, but no equilibrium between the two forms was observed
      and surprisingly, the hexameric assemblies observed in the crystal structure of
      the human ckshs2 homolog were not detected. These apparent discrepancies between
      proteins that display cross-complementation address the question of the control
      of the cks oligomerization process and its link to the biological function.

PMID- 7729537
TI  - cDNA cloning of a new putative ATPase subunit p45 of the human 26S proteasome, a
      homolog of yeast transcriptional factor Sug1p.
AB  - The nucleotide sequence of a cDNA that encodes a new regulatory subunit, named
      p45, of the 26S proteasome of human hepatoblastoma HepG2 cells has been
      determined. The polypeptide predicted from the open reading frame consists of 406
      amino acid residues with a calculated molecular weight of 45770 and isoelectric
      point of 8.35. The sequences of several fragments of bovine p45, determined by
      protein chemical analyses, spanning 27% of the complete structure, were found to
      be in excellent accord with those deduced from the human cDNA sequence. Computer
      analysis showed that p45 belongs to a family of putative ATPases which includes
      regulatory components of 26S proteasomes. The overall structure of p45 was found
      to be homologous to that of yeast Sug1p, which has been identified as a
      transcriptional factor. It is closely similar, but not identical to the sequence
      reported for Trip1, a functional homolog of Sug1p in human tissues. These results
      are consistent with the possibility that Sug1-like proteins with distinct
      sequence function in transcription and protein degradation in human cells.
      However, the alternative hypothesis, that the same gene locus encodes both p45
      and Trip1, cannot be excluded on the basis of such closely similar sequences. In
      either case, both proteins are likely to function equivalently well in either
      transcription or protein degradation.

PMID- 7729538
TI  - Magnesium-independent activation of inward-rectifying K+ channels in Vicia faba
      guard cells.
AB  - The activation of inward-rectifying K+ channels in guard cells at membrane
      potentials negative of the K+ equilibrium potential is important for their
      cellular function as proton pump-driven K+ uptake pathways during stomatal
      opening. In animal cells the voltage-dependence of inward-rectifying K+ channels
      is produced to a large extent by intracellular magnesium block. In guard cells,
      when cytosolic Mg2+ was either 3 mM or < 1 microM, activation times, deactivation
      times and the steady-state voltage-dependence of K+ channels remained unchanged.
      It is discussed that the activation mechanism of inward-rectifying K+ channels in
      guard cells is independent of intracellular Mg2+ block.

PMID- 7729539
TI  - Modulation of endothelin receptor expression in human vascular smooth muscle
      cells by interleukin-1 beta.
AB  - Endothelin may play a role in atherosclerosis as it causes smooth muscle cell
      proliferation and its levels are elevated in patients with atherosclerosis. We
      report that interleukin-1 beta is a potent inducer of endothelin receptor
      expression in cultured human vascular smooth muscle cells. The effect is dose-
      and time-dependent and is due to an increase in receptor number. Endothelin
      receptor mRNA levels are also elevated. Interleukin-1 beta is a major regulator
      of endothelin release so, together with its effects on endothelin receptors, it
      may be responsible for a generalized activation of the endothelin system in
      diseased vessels.

PMID- 7729540
TI  - The second intron of the human galectin-3 gene has a strong promoter activity
      down-regulated by p53.
AB  - Galectin-3 is a galactose-specific lectin which has been shown to be involved in
      several biological functions such as cell growth regulation, cell aggregation and
      cell differentiation. The partial cloning of the human genomic sequences reveals
      the presence of a 651 bp intron, 18 bp downstream of the translation initiation
      site. This intron contains several regulatory elements found in many eukaryotic
      genes. This sequence, when inserted upstream of a promoter-free luciferase gene,
      induces the expression of luciferase, demonstrating the promoter activity of the
      intron upon transfection in human or murine cells. This promoter activity is down
      modulated by wild-type p53 but not by a mutated form of p53.

PMID- 7729541
TI  - Interaction of murine monoclonal subunit-specific antibodies with
      phosphofructokinase-1 from Saccharomyces cerevisiae.
AB  - Murine monoclonal subunit-specific antibodies against heterooctameric
      phosphofructokinase-1 from Saccharomyces cerevisiae exhibiting no cross
      reactivity were purified and characterized regarding complex formation with the
      native enzyme, immunological reactivity to the SDS-denatured subunits originating
      from native and proteolytically truncated phosphofructokinase, and protection
      against proteolytic degradation. Strong complex formation was found with one
      alpha-specific antibody. Western blotting employing different enzyme forms
      allowed to localize epitope sites of the alpha-polypeptide chain. Monoclonal
      antibodies protect phosphofructokinase-1 against chymotryptic degradation.

PMID- 7729542
TI  - The light-harvesting chlorophyll a-c-binding protein of dinoflagellates: a
      putative polyprotein.
AB  - The principle light-harvesting chlorophyll a-c-binding protein of Amphidinium
      carterae of 19 kDa is encoded as a polyprotein translated from a 6.1 kb mRNA. The
      cDNA sequences indicate that each derived polypeptide is contiguous with the next
      and that the mature peptides are formed by cleavage at a C-terminal arginine
      residue. Comparison of the amino-acid sequences shows the Amphidinium protein to
      be most closely related to the fucoxanthin-chlorophyll-protein (Fcp) of
      Phaeodactylum and less related to the chlorophyll a-b-binding (Cab) proteins
      including those from Euglena.

PMID- 7729543
TI  - Functional consequences of mutation Asn326-->Leu in the 4th transmembrane segment
      of the alpha-subunit of the rat kidney Na+, K(+)-ATPase.
AB  - Site-specific mutagenesis was used to replace Asn326 in transmembrane segment M4
      of the ouabain-insensitive alpha 1-isoform of rat kidney Na+, K(+)-ATPase. Mutant
      Asn326-->Leu was functional as demonstrated by the ability of COS cells
      expressing the mutant enzyme to grow in the presence of ouabain. In three
      independent assays encompassing Na+ titrations of Na+,K(+)-ATPase activity, Na(+)
      ATPase activity, and phosphorylation from ATP, the Asn326-->Leu mutant displayed
      a reduced apparent affinity for Na+. By contrast, this mutant exhibited a
      slightly increased apparent affinity for K+ relative to the wild-type enzyme. In
      the presence of Na+ without K+, the Asn326-->Leu mutant hydrolyzed ATP at a high
      rate corresponding to 32% of the maximal Na+,K(+)-ATPase activity, and the rate
      of dephosphorylation of the phosphoenzyme intermediate was enhanced in the mutant
      relative to that of the wild-type enzyme. Oligomycin, known to stabilize the
      Na(+)-occluded phosphoenzyme intermediate, reduced the dephosphorylation rate of
      the mutant and increased the steady-state phosphoenzyme level formed by the
      mutant at least 3-fold, whereas an increase in the steady-state phosphoenzyme
      level of only 10-15% was determined for the wild-type enzyme. The molecular
      turnover number for the Na+,K(+)-ATPase reaction, calculated when the steady
      state phosphoenzyme level obtained in the presence of oligomycin was taken as a
      measure of the concentration of active sites, was slightly reduced relative to
      that of the wild-type enzyme. The data are discussed in terms of a role for
      Asn326 in binding of cytoplasmic Na+ and in mediation of inhibition of
      dephosphorylation.

PMID- 7729544
TI  - Determination of the [Fe4S4]Cys4 cluster geometry of Desulfovibrio africanus
      ferredoxin I by 1H NMR spectroscopy.
AB  - 1D and 2D 1H NMR studies of the Fe4S4 cluster containing ferredoxin I from
      Desulfovibrio africanus have been carried out with the aim of determining the
      geometry of the cluster linkages with the 4 Cys side chains that bind the
      cluster. This required the Cys beta CH resonances of the oxidised protein to be
      sequence-specifically and stereo-specifically assigned, and this was accomplished
      by a combination of TOCSY and NOE measurements, allied to model building based on
      X-ray structures of related ferredoxins. An analysis of the estimated hyperfine
      shifts of the Cys beta CH resonances with a Karplus-type equation relating the
      shifts to iron-sulfur-beta carbon-beta proton dihedral angles, taken together
      with the relative relaxation rates of the two beta CH2 resonances, estimated from
      their linewidths, then allowed the iron-sulfur-beta-carbon-alpha-carbon dihedral
      angles to be determined. A novel representation of the NMR data is presented
      which shows that the cluster dihedral angles are uniquely determined by the NMR
      data. The analysis reveals that the dihedral angles for D. africanus ferredoxin I
      are similar to the corresponding angles of other ferredoxins even though there
      are differences in their 1H NMR spectra. The sequence-specific and stereospecific
      assignments have been extended by analogy to the related Fe4S4-containing D.
      gigas ferredoxin I, and the stereospecific assignments to the Fe4S4-containing
      Thermococcus litoralis ferredoxin.

PMID- 7729545
TI  - Crystallization and preliminary X-ray analysis of UMP/CMP-kinase from
      Dictyostelium discoideum with the specific bisubstrate inhibitor P1-(adenosine
      5')-P5-(uridine 5')-pentaphosphate (UP5A).
AB  - UMP/CMP-kinase (UK) from the slime mold Dictyostelium discoideum has been
      purified to high homogeneity and co-crystallized with the bisubstrate inhibitor
      P1-(adenosine 5')-P5-(uridine 5')-pentaphosphate (UP5A). UP5A binds to UK with a
      dissociation constant (Kd) of 3 +/- 0.5 nM at 25 degrees C and pH 7.5. This is
      some 50-fold tighter than the binding of P1,P5-(diadenosine 5')-pentaphosphate
      (AP5A, Kd = 160 +/- 15 nM). AP5A is a bisubstrate inhibitor that is specific for
      adenylate kinase. The crystals have the symmetry of the tetragonal space group
      P4(1)2(1)2 or its enantiomorph P4(3)2(1)2. The unit cell dimensions are a = b =
      78.5 A and c = 101.4 A. The crystals diffract to a Bragg spacing of 2.1 A.

PMID- 7729546
TI  - Assignment to chromosome 11 of mouse p68 RNA helicase gene (Hlr1) and pseudogene
      (Hlr1-ps1).
AB  - The gene encoding murine p68 RNA helicase (Hlr1) was mapped to the distal portion
      of mouse chromosome 11 by linkage analysis of DNA restriction length
      polymorphisms using an interspecific genetic backcross between (C57BL/6J x
      SPRET/Ei) F1 hybrids and SPRET/Ei mice. A closely related gene (Hlr1-ps1) was
      identified, isolated, and mapped to the proximal part of the same chromosome.
      Sequence analysis and PCR results suggest that Hlr1-ps1 is a pseudogene, flanked
      by DNA stretches similar to mouse insertion element IE118.

PMID- 7729547
TI  - Differential effects of an acyl-coenzyme A:cholesterol acyltransferase inhibitor
      on HDL-induced cholesterol efflux from rat macrophage foam cells.
AB  - When rat macrophages were converted to foam cells with acetylated low density
      lipoprotein (acetyl-LDL) and then reacted with high density lipoprotein (HDL) and
      an inhibitor of acyl-coenzyme A:cholesterol acyltransferase (58-035) (sequential
      incubation system), 58-035 did not enhance HDL-induced cholesterol efflux. In
      contrast, when macrophages were exposed to acetyl-LDL in the presence of both HDL
      and 58-035 (simultaneous incubation system), HDL-induced cholesterol efflux was
      enhanced 1.6-fold by 58-035. Cholesterol efflux with HDL alone was 2-fold greater
      in simultaneous incubation than in sequential incubation. These results suggest
      the presence of an efficient cholesterol efflux pathway in simultaneous
      incubation which is not available in sequential incubation. This pathway, which
      we refer to as the neutral cholesterol ester hydrolase-independent pathway, is
      characterized by the efflux of lysosome-derived cholesterol without re
      esterification.

PMID- 7729548
TI  - Role of lysine-195 in the KMSKS sequence of E. coli tryptophanyl-tRNA synthetase.
AB  - Lysine 195 in the K195 MSKS sequence of E. coli tryptophanyl-tRNA synthetase
      (TrpRS) was replaced with alanine. The resulting K195A mutant TrpRS had
      essentially unchanged Km values for ATP and Trp, but a 1500-fold decreased kcat
      in a pyrophosphate-ATP exchange reaction. This large decrease in kcat reduces the
      rate of aminoacyladenylate formation (step 1) to a rate comparable to the rate of
      aminoacylation of tRNA(Trp) (step 2) by the K195A mutant enzyme. Both the TIGN
      and KMSKS sequences are important for step 1 of class I aminoacyl-tRNA synthetase
      reactions.

PMID- 7729549
TI  - Complete sequence and characterization of the major sperm nuclear basic protein
      from Mytilus trossulus.
AB  - We have characterized the major protamine-like protein (PL-III) from the sperm of
      the mussel Mytilus trossulus. The molecular mass of the main protein component of
      PL-III, determined by mass spectrometry using fast atom bombardment and matrix
      assisted laser desorption ionization was 11304 +/- 6 Da. The complete protein
      sequence was established by Edman degradation and the molecular mass derived from
      this sequence coincides with that experimentally determined. The protein has a
      sedimentation coefficient s20,w = 1.15 +/- 0.5 S which is consistent with a
      random coil of radius of gyration 34.3 +/- 1.4 A.

PMID- 7729550
TI  - High expression of a novel carnitine palmitoyltransferase I like protein in rat
      brown adipose tissue and heart: isolation and characterization of its cDNA clone.
AB  - To characterize energy metabolism in rat brown adipose tissue (BAT), we carried
      out differential screening of a cDNA library of BAT with a cDNA probe of white
      adipose tissue (WAT) and isolated one cDNA clone. It contained a single open
      reading frame of 2,316 bases which encodes a protein of 88.2 kDa. The predicted
      amino acid sequence showed the highest homology (62.6%) with that of rat
      carnitine palmitoyltransferase I (CPTI). The transcript corresponding to this
      cDNA was found to be abundantly expressed in BAT and heart. Therefore, the
      isolated clone is concluded to encode a CPTI like protein expressed in BAT and
      heart.

PMID- 7729551
TI  - A novel antiporter activity catalyzing sodium and potassium transport from right
      side-out vesicles of E. coli.
AB  - Downhill sodium efflux from right-side-out E. coli membrane vesicles was found to
      be stimulated by negative electric potential, as has been reported earlier
      [Bassilana et al., Biochemistry 23 (1984) 1015-1022], and in agreement with the
      concept of electrogenic Na+/nH+ antiporters with n > 1. However, sodium efflux
      was much more accelerated by positive electric potential, indicating the
      operation of another sodium transport system. delta pH (alkaline inside), created
      by a pH shift from 8.5 to 6.8 in the medium was found to drive sodium efflux
      against its concentration gradient, but only when the vesicles had been loaded
      with both Na+ and K+. Efflux of K+ against the concentration gradient was also
      observed under these conditions. When the vesicles were loaded separately with
      sodium tricine or potassium tricine, no K+ efflux and insignificant Na+ efflux
      were observed. We propose that there are at least two different mechanisms
      responsible for Na+ efflux in E. coli vesicles. One is the Na+/nH+ antiporter
      previously described, and the other is a novel Na+,K+/mH+ antiporter.

PMID- 7729552
TI  - The thrombin receptor in human platelets is coupled to a GTP binding protein of
      the G alpha q family.
AB  - The thrombin receptor is a G protein-coupled receptor, but the G proteins
      functionally coupled to this receptor in human platelets are not yet definitively
      identified. Thrombin stimulation of platelets leads to phospholipase C-mediated
      increases in intracellular calcium, and previous studies have suggested that the
      thrombin receptor is coupled to members of the Gq family. We now demonstrate
      direct GTPase activation by thrombin receptor activation peptide (TRAP) in human
      platelet membranes, and specific inhibition of TRAP-activated GTPase by
      antibodies to Gq. These data demonstrate functional coupling of the thrombin
      receptor to a member of the Gq family.

PMID- 7729553
TI  - Oligomannose-coated liposomes as an adjuvant for the induction of cell-mediated
      immunity.
AB  - The effect of the coating of ovalbumin-reconstituted liposomes with various
      oligosaccharides on their immunogenicity was investigated in mice. The coating of
      liposomes with oligomannose or yeast mannan drastically enhanced their ability to
      induce an ovalbumin-specific delayed-type footpad swelling response with a peak
      at 24 to 48 h post-challenge. Among various oligosaccharides tested, only those
      with mannose residue at the nonreducing termini manifested the activity when
      applied to liposomes. Since such oligosaccharides are ubiquitously found in the
      body, these results suggested the usefulness of oligomannose-coated liposomes as
      a safe adjuvant for the induction of cell-mediated immunity.

PMID- 7729554
TI  - Inhibition of 20-kDa myosin light chain exchange by monoclonal antibodies against
      17-kDa myosin light chain.
AB  - Two anti-17,000 Da myosin light chain (LC17) monoclonal antibodies (MM2 and
      MM10), which increase the actin-activated Mg(2+)-ATPase activity of
      dephosphorylated smooth muscle myosin, inhibited the exchange of the 20,000 Da
      regulatory light chain of myosin (LC20). MM2, which shows higher potency of
      activation of ATPase activity, inhibited the exchange more extensively than MM10,
      suggesting that there is a correlation between the activation of ATPase activity
      and the inhibition of the LC20 exchange. The inhibition of the exchange was
      observed for intact myosin and heavy meromyosin but not subfragment 1, suggesting
      that the heavy chain at the head-rod junction is involved in the inhibition of
      LC20 exchange by anti-LC17 antibodies. Alternatively, the interaction between the
      two heads of the myosin molecule may influence the inhibition of LC20 exchange.
      These results suggest that LC20 interacts with both LC17 and the heavy chain, and
      the interaction between LC20 and LC17 is involved in the activation of actin
      activated ATPase activity of smooth muscle myosin.

PMID- 7729555
TI  - Major allergen Phl p Vb in timothy grass is a novel pollen RNase.
AB  - A cDNA coding for the major group V allergen Phl p Vb was isolated from a timothy
      grass pollen cDNA library by immunoscreening with a specific monoclonal antibody.
      It was discovered for the first time that the recombinant Phl p Vb pollen
      allergen after expression and purification has ribonuclease activity. High
      homology of Phl p Vb to other group V allergens in grass pollen indicates similar
      function. By RNase activity gel of natural pollen extract of timothy grass and
      consecutive Western blot analysis of the excised proteins, the RNase active bands
      were shown to be group V allergens. Additionally it was demonstrated that an
      homologous protein to Phl p Vb in the mother plant could be induced by salicylic
      acid. This indicates that group Vb allergens may be involved in host-pathogen
      interactions because in pollen they are quickly exported RNases and in the mother
      plant they depend on a hormone which is related to expression of plant resistance
      genes.

PMID- 7729556
TI  - Site-specific 15N-labelling of oligonucleotides for NMR: the trp operator and its
      interaction with the trp repressor.
AB  - A convenient and economical method is described for the site-specific 15N
      labelling of the 4-amino group of individual cytidine residues in
      oligonucleotides. This is applied to a 20 base-pair oligonucleotide corresponding
      to the trp operator; this oligonucleotide and its complex with the E. coli trp
      repressor are studied by NMR, using 1H-15N HMQC and 15N-edited 1H-1H NOESY
      experiments.

PMID- 7729557
TI  - A quantitative secondary structure analysis of the 33 kDa extrinsic polypeptide
      of photosystem II by FTIR spectroscopy.
AB  - In chloroplast photosystem II, the extrinsic polypeptide of 33 kDa is involved in
      the stabilization the Mn cluster in charge of water splitting and in the
      fulfilment of the Ca(2+)-cofactor requirement for oxygen evolution. The
      conformational analysis of the purified 33 kDa extrinsic polypeptide was carried
      out using FTIR spectroscopy with its self-deconvolution and second derivative
      resolution enhancement as well as curve-fitting procedures. The FTIR
      spectroscopic results showed that the isolated polypeptide is characterized by a
      major proportion beta-sheet conformation (36%) with 27% alpha-helix, 24% turn,
      and 13% beta-antiparallel structures.

PMID- 7729558
TI  - Sequencing and the alignment of structural genes in the nqr operon encoding the
      Na(+)-translocating NADH-quinone reductase from Vibrio alginolyticus.
AB  - We previously cloned a part of nqr operon encoding the Na(+)-translocating NADH
      quinone reductase (NQR) from the marine Vibrio alginolyticus [Hayashi et al.,
      FEBS Lett. 356 (1994) 330-332]. From its nucleotide sequences, four consecutive
      open reading frames (ORF) encoding the gamma-subunit (27.7 kDa), two unidentified
      ORFs of 22.6 kDa and 21.5 kDa, and the beta-subunit (45.3 kDa) were recognized.
      The gene encoding the alpha-subunit was located upstream, and together with the
      recent report by Beattie et al. [FEBS Lett. 356 (1994) 333-338], the nqr operon
      was found to be constructed from six consecutive structural genes, where nqr1,
      nqr3 and nqr6 correspond to the alpha-, gamma-, and beta-subunits, respectively,
      of the NQR complex.

PMID- 7729559
TI  - Gamma-interferon causes a selective induction of the lysosomal proteases,
      cathepsins B and L, in macrophages.
AB  - Previous studies have indicated that acid-optimal cysteine proteinase(s) in the
      endosomal-lysosomal compartments, cathepsins, play a critical role in the
      proteolytic processing of endocytosed proteins to generate the antigenic peptides
      presented to the immune system on major histocompatibility complex (MHC) class II
      molecules. The presentation of these peptides and the expression of MHC class II
      molecules by macrophages and lymphocytes are stimulated by gamma-interferon
      (gamma-IFN). We found that treatment of human U-937 monocytes with gamma-IFN
      increased the activities and the content of the two major lysosomal cysteine
      proteinases, cathepsins B and L. Assays of protease activity, enzyme-linked
      immunosorbant assays (ELISA) and immunoblotting showed that this cytokine
      increased the amount of cathepsin B 5-fold and cathepsin L 3-fold in the
      lysosomal fraction. By contrast, the aspartic proteinase, cathepsin D, in this
      fraction was not significantly altered by gamma-IFN treatment. An induction of
      cathepsins B and L was also observed in mouse macrophages, but not in HeLa cells.
      These results suggest coordinate regulation in monocytes of the expression of
      cathepsins B and L and MHC class II molecules. Presumably, this induction of
      cysteine proteases contributes to the enhancement of antigen presentation by
      gamma-IFN.

PMID- 7729560
TI  - Nuclear magnetic resonance assignments and secondary structure of bovine S100
      beta protein.
AB  - S100 beta is a neurite extension factor and has been implicated in Alzheimer's
      disease and Down's syndrome. It belongs to a group of low molecular weight
      calcium-binding proteins containing the helix-loop-helix calcium binding motif.
      The structure of only one S100 protein, calbindin D9k, which has the lowest
      sequence similarity to the other members of the S100 group has been determined.
      We report the NMR assignments and secondary structure of calcium-free S100 beta.
      The secondary structure is similar to that of calbindin D9k, determined using
      NMR, except that there is clear evidence for an additional well ordered 5-residue
      alpha-helix in S100 beta.

PMID- 7729562
TI  - Health care reform needs critical care.

PMID- 7729561
TI  - Molecular cloning and expression of subunit 12: a non-MCP and non-ATPase subunit
      of the 26 S protease.
AB  - A cDNA encoding subunit 12 (S12) of human erythrocyte 26 S protease has been
      isolated, sequenced and expressed. The cDNA contains an open reading frame that
      encodes a 36.6 kDA protein 96% identical to mouse Mov-34 and 67% identical to its
      Drosophila melanogaster homolog. Based on the high degree of sequence identity
      between human S12, mouse and Drosophila Mov-34 proteins, we conclude that the Mov
      34 gene product is a component of the 26 S protease. Antibodies produced against
      two S12 fragments, Met1-Tyr95 (S12f95) and Met1-Leu205 (S12f205), react with S12
      transferred to nitrocellulose from SDS-PAGE. In contrast, after transfer from
      native gels, the epitope(s) recognized by anti-S12f205 is exposed in the
      regulatory complex but appears to be masked when the regulatory complex
      associates with the multicatalytic protease.

PMID- 7729563
TI  - Workplace redesign.

PMID- 7729564
TI  - Hospital design in the 21st century.

PMID- 7729565
TI  - Anti-retinoic acid monoclonal antibody localizes all-trans-retinoic acid in
      target cells and blocks normal development in early quail embryo.
AB  - Avian cardiovascular development is vitamin A-dependent, and retinoic acid has
      been suggested to be active in this important developmental event. We report here
      that a monoclonal antibody against all-trans-retinoic acid blocks normal
      embryonic development in the quail causing cardiovascular abnormalities typical
      of avian vitamin A deficiency. In whole-mount preparations of stage 5 normal
      quail embryos the fluorescence associated with the antiretinoic acid monoclonal
      antibody localizes in Hensen's node and in caudal area. In stage 7-8 embryos
      fluorescence localizes in heart-forming areas as well as in head mesenchyme, in
      Hensen's node, in nephrotome, and in caudal area. These studies are the first to
      localize endogenous all-trans-retinoic acid during very early stages of normal
      avian development. We propose that all-trans-retinoic acid is biosynthesized in
      its target cells during early avian embryo-genesis and that the availability of
      this signal molecule is spatiotemporally regulated. We conclude that all-trans
      retinoic acid or a closely related metabolite is the physiological form of
      vitamin A required for normal cardiovascular development and for other very early
      developmental events in the quail embryo.

PMID- 7729566
TI  - Depolarization and laminin independently enable bFGF to promote neuronal survival
      through different second messenger pathways.
AB  - This study presents evidence that cellular responsiveness to the neurotrophic
      factor basic fibroblast growth factor (bFGF) can be achieved by at least two
      classes of agents using different initial second messenger pathways. Embryonic
      chick ciliary ganglion neurons plated on polyornithine normally undergo rapid
      cell death in culture and could not be rescued by addition of bFGF. Similarly,
      neither exposure to laminin alone nor low levels of depolarization alone was
      sufficient to promote neuronal survival. In contrast, if ciliary ganglion neurons
      were exposed to bFGF in the presence of either laminin or low levels of
      depolarization, nearly all neurons were rescued from cell death. The observed
      synergistic effect of bFGF and low levels of depolarization required influx of
      calcium since addition of the L-type calcium channel antagonists PN200-110
      completely prevented neuronal survival. The synergistic effect observed between
      laminin and bFGF was independent of changes in intracellular calcium since PN200
      110 failed to block the synergistic effect and because neither addition of bFGF
      to neurons plated on laminin nor direct addition of laminin caused any
      significant changes in intracellular calcium. The ability of laminin to enable
      bFGF to promote neuronal survival could completely be blocked by the addition of
      antibodies to beta 1-integrin, suggesting a calcium-independent integrin-mediated
      response. Taken together, these results suggest that both laminin and
      depolarization can enable bFGF responsiveness by acting through different second
      messenger pathways.

PMID- 7729567
TI  - Evidence for a 90 kDa heat-shock protein gene expression in the amphibian oocyte.
AB  - In order to study expression of a 90-kDa heat-shock protein during amphibian
      oogenesis at physiological temperature, we isolated a Pleurodeles waltl hsc90
      cDNA by screening an ovarian cDNA library with a chicken hsp90 cDNA probe. The
      cDNA thus obtained--named Pw90--shows a high homology level with the hsp90 gene
      in other species. RNase protection analysis led us to conclude that this sequence
      is part of the cognate gene hsc90 and is constitutively expressed in oocytes.
      Furthermore, results of quantitative Northern blot analysis, as well as in situ
      hybridizations on oocyte sections or lampbrush chromosome spreads, provide
      evidence for expression of hsc90 transcripts at every stage of oogenesis.
      Moreover, they point to the fact that an accumulation of transcripts occurs very
      early in oogenesis. Simultaneously, the expression of HSC90-related protein was
      analyzed on Western blots using a monoclonal antibody (AC88) and a polyclonal
      antibody (AP90Ct) raised against the Pleurodeles C-terminal part of HSC90. We
      provide evidence for a net accumulation of HSC90-related protein in oocytes.
      Immunolocalization shows that a nuclear transfer occurs in the course of
      oogenesis and leads to a concentration equilibrium between cytoplasm and nucleus
      in stage VI oocytes.

PMID- 7729568
TI  - Galectin-7, a human 14-kDa S-lectin, specifically expressed in keratinocytes and
      sensitive to retinoic acid.
AB  - A cDNA encoding a novel member of the S-lectin family has been cloned from human
      epidermis. The 14-kDa protein of pI7 predicted by the 136-amino-acid open reading
      frame of the sequence was called galectin-7 according to the presently accepted
      nomenclature. A GST fusion protein authentified the lactose-binding properties
      expected for a member of this lectin subfamily. Galectin-7 was identified on two
      dimensional gels of keratinocyte protein extracts. Differential and in situ
      hybridizations indicate that this lectin is specifically expressed in
      keratinocytes. It is expressed at all stages of epidermal differentiation (i.e.,
      in basal and suprabasal layers). It is moderately repressed by retinoic acid, a
      behavior contrasting with those of other keratinocyte markers sensitive to this
      agent, which, either basal, are induced, or suprabasal, are repressed. This
      effect of retinoic acid on a keratinocyte cell type marker such as galectin-7 is
      more reminiscent of its metaplasiogenic effect in vivo than of its inhibitory
      effect on terminal epidermal differentiation in vitro. This interpretation is
      supported by the fact that in chick epidermis a 14-kDa S-lectin is suppressed
      during retinoic acid-induced mucous metaplasia.

PMID- 7729569
TI  - Intrinsic differences in axonal growth from crayfish fast and slow motoneurons.
AB  - The motoneurons innervating the fast and slow flexor muscles in the abdomen of
      crayfish form morphologically distinct motor terminals. Axons of the fast flexor
      (FF) motoneurons, which innervate the large (fast) flexor muscle, produce
      extensive motor terminal arbors with many branches. Axons of the slow flexor (SF)
      motoneurons, which innervate the thin (slow) flexor muscle, produce small
      terminal arbors with many fewer branches. To determine whether intrinsic factors
      contribute to these differences in terminal arbors, we compared regenerating
      axonal arbors from these two populations of motoneurons. We used an explant of
      the crayfish nerve cord in which axons from the FF and SF motoneurons regenerate
      on a homogeneous substrate. We found that regardless of the substrate, FF motor
      axons produced arbors with a greater total length and a greater number and
      density of branches than SF motor axons. These differences in regenerated arbors
      persisted in defined medium and in the absence of impulse activity, indicating
      that they result from intrinsic, neuron-specific factors. The greater branching
      of the FF motor axons may be related to differences in growth cones: growth cones
      of FF axons were significantly larger with more filopodia than growth cones of SF
      axons.

PMID- 7729570
TI  - Differential binding of oocyte-type and somatic-type 5S rRNA to TFIIIA and
      ribosomal protein L5 in Xenopus oocytes: specialization for storage versus
      mobilization.
AB  - We studied the pathway of 5S ribosomal RNA (rRNA) during oogenesis in Xenopus
      from its storage in the cytoplasm to incorporation into ribosomes in the nucleus.
      Ribonucleoprotein particle (RNP) assembly assays reveal striking differences in
      the behavior of oocyte-type and somatic-type 5S rRNA after microinjection into
      stage II, III, or IV oocytes or into the cytoplasm of stage V-VI oocytes.
      Microinjected oocyte-type 5S rRNA predominantly interacts with the 5S rRNA gene
      specific transcription factor IIIA (TFIIIA) to form storage 7S RNPs. In contrast,
      microinjected somatic-type 5S rRNA predominantly interacts with ribosomal protein
      L5 to form 5S RNPs, which are precursors to ribosome assembly. In addition, a
      greater amount of somatic-type 5S rRNA accumulates in the nucleus and is
      assembled into 60S ribosomal subunits. Thus, a slight difference in nucleotide
      sequence results in differential binding of 5S rRNA to TFIIIA and L5,
      specializing oocyte-type for storage in the oocyte cytoplasm and somatic-type for
      rapid mobilization and ribosome assembly. When oocyte-type and somatic-type 5S
      rRNA molecules were microinjected into the nucleus of stage V-VI oocytes in
      excess of other ribosomal components, the nucleocytoplasmic distribution of both
      types of RNA was similar, but the distinctive protein associations were
      maintained. In contrast, the behavior of oocyte-type and somatic-type 5S rRNA
      gradually synthesized in situ from microinjected cloned genes was similar,
      suggesting that nascent RNA is rapidly and directly recruited into ribosomes,
      thus bypassing an excursion into the cytoplasm prior to ribosome assembly.

PMID- 7729571
TI  - Paraxis: a basic helix-loop-helix protein expressed in paraxial mesoderm and
      developing somites.
AB  - During vertebrate embryogenesis, cells from the paraxial mesoderm coalesce in a
      rostral-to-caudal progression to form the somites. Subsequent
      compartmentalization of the somites yields the sclerotome, myotome, and
      dermatome, which give rise to the axial skeleton, axial musculature, and dermis,
      respectively. Recently, we cloned a novel basic helix-loop-helix (bHLH) protein,
      called scleraxis, which is expressed in the sclerotome, in mesenchymal precursors
      of bone and cartilage, and in connective tissues. Here we report the cloning of a
      bHLH protein, called paraxis, which is nearly identical to scleraxis within the
      bHLH region but diverges in its amino and carboxyl termini. During mouse
      embryogenesis, paraxis transcripts are first detected at about Day 7.5 postcoitum
      within primitive mesoderm lying posterior to the head and heart primordia.
      Subsequently, paraxis expression progresses caudally through the paraxial
      mesoderm, immediately preceding somite formation. Paraxis is expressed at high
      levels in newly formed somites before the first detectable expression of the
      myogenic bHLH genes, and as the somite becomes compartmentalized, paraxis becomes
      downregulated in the myotome. Paraxis and scleraxis are coexpressed in the
      sclerotome, but paraxis expression declines soon after sclerotome formation,
      whereas scleroaxis expression increases in the sclerotome and its derivatives.
      The sequential expression of paraxis and scleraxis in the paraxial mesoderm and
      somites suggests that these bHLH proteins may comprise part of a regulatory
      pathway involved in patterning of the paraxial mesoderm and in the establishment
      of somitic cell lineages.

PMID- 7729572
TI  - Kinetics of the inhibition of axonal defasciculation and arborization mediated by
      carbohydrate markers in the embryonic leech.
AB  - We studied carbohydrate interactions that mediate the targeting of sensory
      afferents in the synaptic neuropil of segmental central nervous system (CNS)
      ganglia in the embryonic leech. First, we determined the rate of sensory afferent
      development in vivo, and then we devised a culture system that permits the normal
      patterning of their projections in the CNS and PNS to proceed at 92% the normal
      rate. Using this in vitro system, we analyzed the mannose-specific recognition
      that mediates the defasciculation and arborization of sensory afferents in the
      CNS neuropil after they have tracked through peripheral nerves as a tight axon
      bundle. Sensory afferent defasciculation and arborization in the neuropil were
      inhibited by culturing embryos in Fab fragments directed against the mannose
      containing surface epitope of sensory afferents. We demonstrate that the rate at
      which separately extending axons or their branches are lost from the neuropil can
      be modeled by a first-order decay process. These kinetic studies indicate that
      the loss of each separately extending axon or branch is an independent event.
      This suggests that sensory afferent projections extend autonomously across the
      target region in the search of their appropriate postsynaptic partners.

PMID- 7729573
TI  - Glycoprotein complexes interacting with cellulose in the "cell print" zones of
      the Dictyostelium discoideum extracellular matrix.
AB  - Cellulose is one of the commonest structural biopolymers. How cellulose is
      organized in extracellular matrices is a mystery. Here we investigate a model
      system, the extracellular matrix (ECM) of Dictyostelium discoideum which is
      composed of proteins and cellulose. A group of glycoproteins, the sheathins,
      which colocalize with cellulose in the ECM of D. discoideum are characterized.
      Sheathins are dimeric or trimeric forms of molecular mass 53-68 kDa, where the
      monomers are 12-35 kDa. The sheathin subunits are similar but not identical
      proteins. The sheathin family comprises sheathin 68, (68-kDa trimer); sheathin
      62, (62-kDa dimer); sheathin 55, (55-kDa dimer), and sheathin 53, (53-kDa dimer).
      The subunits which assemble into the four sheathins represent at least three gene
      products: ShC, ShD, and ShE which are linked by disulphide bonds. Protein
      sequence analysis shows two of the sheathin genes encode products ShC and ShD
      with very similar amino terminal sequences. This group of D. discoideum ECM
      glycoproteins has homology with two other much larger ECM proteins of D.
      discoideum, ST430 and ST310, which are located in a more dispersed fashion in the
      ECM. Sheathins are tightly but non-covalently associated with the ECM, and this
      association requires strong denaturing conditions for disruption, e.g., SDS or 8
      M urea. Sheathins form a component of the "cell prints" which are believed to
      have a role in cell-ECM interactions and slug cell migration.

PMID- 7729574
TI  - Embryonic stem cells express neuronal properties in vitro.
AB  - Mouse embryonic stem (ES) cells cultured as aggregates and exposed to retinoic
      acid are induced to express multiple phenotypes normally associated with neurons.
      A large percentage of treated aggregates produce a rich neuritic outgrowth.
      Dissociating the induced aggregates with trypsin and plating the cells as a
      monolayer results in cultures in which a sizable percentage of the cells have a
      neuronal appearance. These neuron-like cells express class III beta-tubulin and
      the neurofilament M subunit. Induced cultures express transcripts for neural
      associated genes including the neurofilament L subunit, glutamate receptor
      subunits, the transcription factor Brn-3, and GFAP. Levels of neurofilament L and
      GAD67 and GAD65 transcripts rise dramatically upon induction. Physiological
      studies show that the neuron-like cells generate action potentials and express
      TTX-sensitive sodium channels, as well as voltage-gated potassium channels and
      calcium channels. We conclude that a complex system of neuronal gene expression
      can be activated in cultured ES cells. This system should be favorable for
      investigating some of the mechanisms that regulate neuronal differentiation.

PMID- 7729575
TI  - Electroreceptors and mechanosensory lateral line organs arise from single
      placodes in axolotls.
AB  - The lateral line system in salamanders consists of mechanoreceptive neuromasts
      and pit organs, distributed in lines on the head and trunk, and electroreceptive
      ampullary organs located adjacent to the cephalic lines of mechanoreceptors.
      Although numerous studies have documented that neuromast and pit organs and the
      cranial nerves that innervate these receptors arise from a dorsolateral series of
      placodes, there is no agreement concerning the number of these placodes, the
      specific groups of receptors that arise from them, or the embryonic origin of
      ampullary organs. A developmental model was recently proposed (Northcutt et al.,
      1994) in which all these placodes, except for the most posterior one, elongate to
      form sensory ridges whose central zones initially form neuromast and pit organ
      primordia and whose lateral zones subsequently form ampullary primordia. To test
      this model, individual placodes were unilaterally extirpated, or placodes from
      pigmented wild-type axolotl embryos were homotopically or heterotopically
      transplanted into albino hosts. Extirpation resulted in the loss of all three
      receptor classes, and both homotopic and heterotopic transplants produced
      pigmented receptors of all three classes in albino hosts. The receptors in the
      heterotopic transplants still formed lines which occasionally retained their
      normal orientation despite differentiating in an ectopic environment. These
      experiments demonstrated that, as previously postulated, specific lines of
      neuromasts and pit organs do arise from each placode, and ampullary organs also
      arise from many of the same placodes. The distribution of receptors that develop
      following incomplete extirpation or heterotopic transplantation also indicates
      that each placode is patterned regarding receptor classes and orientation prior
      to sensory ridge formation.

PMID- 7729576
TI  - Growth cones of dorsal root ganglion but not retina collapse and avoid
      oligodendrocytes in culture.
AB  - Axons in the central nervous system of mature mammals generally fail to
      regenerate following injury. Although the reason for this regenerative failure
      remains unknown, several lines of evidence suggest that it is due to
      nonpermissiveness of oligodendrocytes for axonal elongation. However, most of the
      in vitro experiments carried out so far used neural-crest-derived peripheral
      neurons to test the permissiveness of oligodendrocytes, although studying the
      interactions between central neurons and oligodendrocytes is crucially important
      for elucidating their roles in vivo. In this study we cultured retinas and dorsal
      root ganglia of the chick embryo with oligodendrocytes obtained from postnatal
      rat spinal cord and performed time-lapse analysis. Oligodendrocytes were
      identified with galactocerebroside antibody. Retinal growth cones readily grew
      over oligodendrocytes, while growth cones of the dorsal root ganglion collapsed
      and grew away on contacting the oligodendrocytes. Correspondingly, neurite-free
      areas centered by oligodendrocytes were formed behind growth cones in DRG
      oligodendrocyte but not in retina-oligodendrocyte co-culture. These observations
      suggest the possibility that responsiveness of growth cones to oligodendrocytes
      is dependent on neuronal type.

PMID- 7729577
TI  - The chick Brachyury gene: developmental expression pattern and response to axial
      induction by localized activin.
AB  - The mouse Brachyury gene (T) is required in notochord differentiation and
      posterior mesoderm formation during axial development. We have isolated the chick
      homologue of T(Ch-T) and determined its putative protein sequence and expression
      pattern during embryogenesis. Ch-T is expressed in the epiblast close to and
      within the primitive streak, in early migrating mesoderm and in the notochord. In
      later stages Ch-T expression is found in the tail bud and in the entire
      notochord. The notochord expression ceases in an anterior-posterior wave when the
      formation of the body anlage is completed. This pattern is consistent with those
      reported for the expression of the mouse T gene and the T homologues of Xenopus
      laevis and zebrafish, suggesting that the mechanisms of embryonic pattern
      formation are highly conserved in all vertebrates. The N-terminal half of Ch-T
      shows a very high degree of sequence identity with the corresponding region of
      mouse T which has DNA-binding activity, and with the N-terminal half of Xenopus
      (Xbra) and zebrafish (Ntl) T protein. Finally, we have analyzed the effects of
      activin A on Ch-T induction and axis formation. Localized activin A treatment of
      prestreak blastoderms results in ectopic Ch-T expression that correlates with
      formation of second primitive streaks or with repositioning of the site of single
      streak origin (Cooke et al., 1994). These results strengthen the previous
      evidence that Brachyury activation is an early response to axis-inducing signals
      in vivo.

PMID- 7729578
TI  - Electrical activity suppresses nicotinic acetylcholine receptor gamma subunit
      promoter activity.
AB  - Nicotinic acetylcholine receptors are pentameric, transmembrane, ligand-gated ion
      channels critical for neuromuscular signal transmission. Prior to innervation,
      the genes encoding these receptors are expressed in nuclei throughout the muscle
      fiber. Muscle innervation leads to a dramatic decrease in expression of these
      genes in extrasynaptic nuclei. This reduction in gene expression can be reversed
      by muscle denervation. The effects of denervation on receptor gene expression can
      be blocked by electrical stimulation of muscle using extracellular electrodes.
      The molecular mechanisms by which muscle electrical activity leads to altered
      patterns of nicotinic acetylcholine receptor gene expression are not well
      understood. Using an in vitro electrical stimulation paradigm to induce muscle
      activity, we have been able to mimic the effect of innervation on extrasynaptic
      acetylcholine receptor gene expression. We have found that a 93-bp region of 5'
      flanking DNA, spanning nucleotides -150 to -57 relative to the transcription
      start site of the gamma subunit gene, is required for the suppression of gene
      expression in response to muscle activity. Sequences downstream of this region
      are transcriptionally active but are not responsive to muscle activity. However,
      these downstream sequences become responsive to muscle activity when placed under
      the control of the gamma subunit muscle-specific enhancer.

PMID- 7729579
TI  - Surface expression of the pre-beta subunit of fertilin is regulated at a post
      translational level in guinea pig spermatids.
AB  - During spermiogenesis in the guinea pig, the spermatid plasma membrane becomes
      sequentially segregated into three domains of distinct composition. We have
      previously shown that plasma membrane proteins appear on the cell surface in a
      temporally regulated manner such that proteins localized to the same domain reach
      the surface membrane at the same time in sperm development. Fertilin is a cell
      surface protein restricted to the whole head of testicular sperm; like other
      proteins restricted to this membrane domain, it does not appear on the cell
      surface until late (steps 11-13) in spermiogenesis. Using confocal microscopy of
      immunofluorescently labeled testicular sections, we demonstrate that the pre-beta
      subunit of fertilin is present in pachytene spermatocytes. It is initially
      observed in long, strand-like structures that likely represent the endoplasmic
      reticulum; it later appears in a punctate distribution in the cytoplasm of early
      spermatids prior to its appearance on the surface membrane in late elongating
      spermatids. Immunoblotting experiments confirm the presence of the fertilin pre
      beta subunit in spermatocytes and early spermatids at the same apparent molecular
      weight as in later stages. These results suggest that the appearance of fertilin
      pre-beta subunit on the spermatid surface is regulated by a post-translational
      mechanism.

PMID- 7729580
TI  - Characterization of chicken syndecan-3 as a heparan sulfate proteoglycan and its
      expression during embryogenesis.
AB  - Syndecan-3 is one of four identified members of a family of transmembrane
      proteoglycans (the syndecans) that possess highly similar cytoplasmic and
      transmembrane domains and may function as extracellular matrix receptors and/or
      low affinity receptors for signaling molecules such as FGF. We previously
      reported the cloning of a partial cDNA for chicken syndecan-3. Here we report the
      isolation of a syndecan-3 cDNA containing additional 5' sequence which includes a
      potential methionine start codon and putative signal sequence. In vitro
      translation of syndecan-3 cDNA in the presence and absence of microsomes suggests
      that the putative signal sequence is functional, suggesting that the cDNA may
      encompass the full coding sequence. We also identify syndecan-3 as a heparan
      sulfate proteoglycan and report its expression pattern during chicken
      embryogenesis using polyclonal antibodies raised against a recombinant fusion
      protein. We detect abundant syndecan-3 expression in the developing brain and
      neural tube, including a striking expression in the floor plate of the neural
      tube. During limb development, syndecan-3 is expressed in the distal mesenchymal
      cells of the limb bud which are undergoing outgrowth in response to the apical
      ectodermal ridge. Syndecan-3 is also transiently expressed during the formation
      of the precartilage condensations of the skeletal elements of the limb and
      subsequently in association with the differentiating osteoblasts of the
      periosteum. Expression is also observed in several areas of tissue interactions
      including the developing lens, otic vesicle, genital ridge, sclerotome, and
      feather buds.

PMID- 7729581
TI  - Duplication of l(2)gd imaginal discs in Drosophila is mediated by ectopic
      expression of wg and dpp.
AB  - We investigated the expression of segment polarity genes during the development
      of overgrowing and duplicating imaginal discs in the lethal overgrowth mutant
      lethal (2) giant discs (l (2) gd) of Drosophila in order to explore the molecular
      basis of hyperplasia and axis establishment in imaginal discs. The expression of
      wingless (wg), detected using an enhancer trap, is initially restricted to a
      ventral sector of the leg disc, as in wild type, but expands toward the opposite
      end of the disc during overgrowth. In the third leg disc, the expanding wg
      expression stripe evolves to a new center of wg expression at the site where a
      duplicate leg is subsequently formed. Expression of decapentaplegic (dpp) also
      begins normally in l (2) gd discs, but the dpp expression domain expands into the
      posterior region of the disc where it enlarges to eventually become the center of
      dpp expression in the duplicate. In l (2) gd homozygotes that are simultaneously
      homozygous for wg or dpp mutations the leg discs overgrow but do not duplicate.
      Thus ectopic wg and dpp expression is associated with and appears to be required
      for disc duplication. The wing discs of l (2) gd homozygotes also show expansion
      of the wg and dpp expression domains, but in this disc wg and dpp mutations
      inhibit overgrowth as well as pattern duplication. Our results raise the
      possibility that hyperplasia in other mutants and in other systems may be caused
      by the misexpression of genes involved in the generation of positional
      information.

PMID- 7729582
TI  - Molecular characterization and expression patterns of a B-type nuclear lamin
      during sea urchin embryogenesis.
AB  - Developmentally regulated, tissue-specific patterns of nuclear lamin expression
      occur during vertebrate embryogenesis, but little is known regarding lamin
      ontogeny during the early development of other phyla. cDNA clones encoding a
      lamin from the sea urchins Strongylocentrotus purpuratus and Lytechinus
      variegatus have been identified, and the full coding region from the former has
      been sequenced. The predicted amino acid sequence indicates that this echinoderm
      lamin is more closely related to vertebrate B-type lamins than to dipteran fly
      and nematode lamins--the only other invertebrate lamins sequenced to date.
      Monoclonal and polyclonal antibodies to sea urchin lamin demonstrate that nuclei
      of unfertilized eggs and embryos exhibit relatively faint immunoreactivity until
      the differentiation of primary mesenchymal cells, the nuclear envelopes of which
      become strongly and selectively labeled by anti-lamin antibodies. Northern blots
      reveal stage-specific fluctuations in a single 4-kb lamin message during early
      development and, together with immunoblotting data, suggest that the increase in
      mesenchymal cell nuclear envelope immunoreactivity is due to a quantitative
      increase in a single type of lamin. These observations demonstrate that, similar
      to vertebrates, cell differentiation in invertebrates can be accompanied by a
      change in lamin expression patterns.

PMID- 7729583
TI  - Pseudocleavage is dispensable for polarity and development in C. elegans embryos.
AB  - The first cleavage of the Caenorhabditis elegans embryo is asymmetrical,
      producing daughters with different cell fates. During the first cell cycle, P
      granules, cytoplasmic components that are segregated to the germ-line, are
      localized to the posterior of the embryo. It has been hypothesized that the
      asymmetrical behavior of the daughters of the first division results from a
      similar localization of developmental determinants. A process called
      pseudocleavage also occurs during the first cell cycle: Anterior cortical
      contractions culminate in a single partial constriction of the embryo called the
      pseudocleavage furrow. Coincident with pseudocleavage, there is an anteriorly
      directed flow of cortical cytoplasm and a posteriorly directed flow of internal
      cytoplasm. Foci of filamentous cortical actin become asymmetrically distributed
      into an anterior cap. Roles for these various first cell cycle events in
      cytoplasmic localization and development have been suggested but remain unclear.
      We have isolated a maternal effect mutation, nop-1(it142), which abolishes the
      anterior cortical contractions and the pseudocleavage furrow. In addition,
      cortical actin foci remain uniformly distributed in most embryos. Despite these
      defects, cytoplasmic and cortical streaming is present and P granules are
      localized to the posterior of early embryos. In most embryos from mutant mothers,
      development proceeds normally and the embryos hatch and grow into fertile adults.
      We conclude that the pseudocleavage contractions and furrow are dispensable for
      the development of C. elegans.

PMID- 7729584
TI  - Ecdysteroid regulation and DNA binding properties of Drosophila nuclear hormone
      receptor superfamily members.
AB  - Pulses of the steroid hormone 20-hydroxyecdysone (20E) trigger the larval-to
      adult metamorphosis of Drosophila by reprogramming gene expression throughout the
      organism. 20E directly induces a small set of early regulatory genes that repress
      their own expression and induce a large set of late secondary-response genes. We
      show here that two members of the Drosophila nuclear hormone receptor
      superfamily, DHR3 and DHR39, are rapidly induced by 20E, in parallel with the
      early regulatory genes. Both genes also require protein synthesis at high 20E
      concentrations for their maximal induction by the hormone. Developmental Northern
      blot analysis reveals that DHR39 is induced in mid third instar larvae and
      expressed throughout most of third instar larval and prepupal development, while
      DHR3 is briefly expressed in late third instar larvae and early prepupae. The 20E
      induction and temporal patterns of DHR3 and DHR39 transcription strongly suggest
      that these genes function together with the early regulatory genes to coordinate
      the complex gene networks that direct the early stages of Drosophila
      metamorphosis. In an initial effort to understand how these two orphan receptors
      might function during development, we examined their DNA binding properties and
      compared them with the known Drosophila nuclear receptor superfamily members that
      are involved in the ecdysteroid response: EcR, Usp, E75A, E78A, and beta FTZ-F1.
      Upon testing all pairwise combinations of these seven proteins on a panel of
      seven oligonucleotides, only EcR and Usp bound DNA as a heterodimer, indicating
      that this interaction is highly specific. With the exception of E78A, which did
      not bind any sequence tested, each of the remaining proteins is able to bind to a
      single consensus AGGTCA half-site; however, each displayed different
      specificities depending on the flanking nucleotide sequence. These observations
      suggest that the 20E-regulated orphan receptors function as monomers to control
      the expression of their target genes.

PMID- 7729585
TI  - Monoclonal antibody MT2 identifies the urodele alpha 1 chain of type XII
      collagen, a developmentally regulated extracellular matrix protein in
      regenerating newt limbs.
AB  - We previously described the upregulation of the MT2 antigen during urodele limb
      regeneration and characterized the MT2 antigen as a 310- to 325-kDa chondroitin
      sulfated glycoprotein with a core protein of 285-300 kDa. In this study, we
      screened a newt blastema cDNA library using monoclonal antibody (mAb) MT2 and
      obtained a 1-kb cDNA fragment, designated Isolate (IS)-1. Subsequent screening of
      the same library using IS-1 cDNA as a probe provided IS-2, a 2.8-kb cDNA. IS-2
      overlaps IS-1 at its 5' end, is highly homologous to a portion of the alpha 1
      chain of the chicken type XII collagen cDNA (alpha 1[XII]), and spans a third of
      the chicken alpha 1[XII] cDNA, from the last 62 amino acids of the second A
      domain of von Willebrand factor to the first two repeats of the fourth
      fibronectin type III domain. The peptide sequence deduced from cDNA IS-2
      demonstrates invariable tryptophan, leucine, threonine, and tyrosine residues
      that are highly conserved among all the fibronectin type III domains within IS-2
      and between corresponding sequences of IS-2 and chicken alpha 1[XII]. A Northern
      blot showed a 10-kb band that corresponds to the size of the chicken alpha 1[XII]
      mRNA. A fusion gene was constructed by inserting the IS-2 cDNA downstream from
      the malE gene of Escherichia coli, which encodes maltose-binding protein (MBP).
      The isopropyl beta-D-thiogalactoside-induced fusion protein had the expected
      molecular weight and reacted to both mAb MT2 and rabbit anti-MBP serum. We
      conclude that mAb MT2 identifies the urodele alpha 1[XII]. The expression pattern
      of the type XII collagen gene in newt limb regenerates was examined by in situ
      hybridization. Type XII collagen transcripts first appeared at 3 days after
      amputation in cells of the basal layer of the wound epithelium. At Day 10, both
      the basal wound epithelial cells and the distal mesenchyme cells were highly
      transcriptionally active. At mid-bud and late-bud blastema stages, wound
      epithelium expression had decreased, whereas the mesenchyme remained strongly
      active in transcription and showed a tendency toward distal regionalization.
      Condensing cartilage showed no signal. Finally, at the late digit stage,
      hybridization became largely restricted to the perichondrium. The in situ results
      suggest a developmental role for type XII collagen in regeneration.

PMID- 7729586
TI  - Anteriorization of CRABP-I expression by retinoic acid in the developing mouse
      central nervous system and its relationship to teratogenesis.
AB  - We have investigated the role that cellular retinoic acid binding protein I
      (CRABP-I) may play in the development of the murine hindbrain. Since the central
      nervous system (CNS) represents a major site of the teratogenic action of
      retinoic acid (RA), we have also determined the effects of exposure of high
      levels of RA on CRABP-I expression within the CNS. Expression of CRABP-I can
      first be detected within the presumptive hindbrain of presomitic mouse embryos
      and later also appears in neural crest cells and neural crest derivatives; it is
      thus tissue specific at these early stages. Exposure of 7.75-day mouse embryos to
      RA induces two phenotypes: one is externally normal and the other is
      exencephalic. In the exencephalic embryos we show that there is abnormal crest
      migration, a fusion of the trigeminal and facial-acoustic ganglia, a rostral and
      lateral shift of the otic vesicle, and a loss of hindbrain rhombomeres.
      Furthermore, and in contrast to in vitro studies, we demonstrate that CRABP-I
      appears to be up-regulated in both phenotypes of mouse embryos treated with RA
      and that this up-regulation is accompanied by an anteriorization of its
      expression within the nervous system. This new CRABP-I expression domain thus
      retains its tissue specificity. The role that CRABP-I may play in normal
      development of the hindbrain and in teratogenesis and the similarity of these
      results to those obtained with various Hox genes are discussed.

PMID- 7729587
TI  - Retinoic acid promotes the differentiation of adrenergic cells and melanocytes in
      quail neural crest cultures.
AB  - The neural crest (NC) generates very diverse neuronal and nonneuronal cell types
      in the vertebrate embryo. Pluripotency and plasticity of NC cells have been
      demonstrated, but the mechanisms whereby extrinsic factors control NC cell
      diversification are still unknown. Here we have investigated in vitro the
      influence of the morphogen retinoic acid (RA) in cultures of quail NC cells
      explanted at different developmental stages, when they start to migrate from the
      neural primordium, and when they reach their target organs. We found that
      addition of RA to mass cultures of early-migrating trunk NC promotes the
      differentiation of melanocytes and adrenergic cells. These responses are dose
      dependent and vary according to the time of RA exposure. Testing RA effect on
      crest-derived cells located in Embryonic Day 3 (E3) somites and in E4 skin showed
      that the adrenergic-promoting action of RA is restricted to early-migratory
      cells, while melanogenic precursors colonizing the skin remain sensitive to RA
      for a longer period. Furthermore, analysis of cephalic and trunk NC clonal
      cultures revealed that RA influences the differentiation of cells when they are
      in a pluripotent state: among the progeny of isolated crest cells, RA
      specifically increases the number of the adrenergic cells, very likely by
      influencing their commitment; moreover, RA stimulates pigment synthesis in the
      melanoblasts. In conclusion, these results demonstrate that RA enhances in vitro
      the differentiation of NC cells and support a role for endogenous retinoids in
      the ontogeny of NC derivatives.

PMID- 7729588
TI  - Activin-A and FGF-2 mimic the inductive effects of anterior endoderm on terminal
      cardiac myogenesis in vitro.
AB  - We recently reported that the differentiation of cultured embryonic precardiac
      myocytes is specifically promoted by anterior lateral plate endoderm from
      Hamburger-Hamilton stage 6 chick embryos. Polypeptide growth factors are probable
      mediators of cardiogenesis during embryonic development. It was previously noted
      that activin-A is a major secretory product of endoderm cultured from chicken
      embryos. Also, fibroblast growth factor-like proteins are present in anterior
      endoderm of stage 6 chick embryos. Therefore, we have examined the cardiogenic
      effects of these growth factors on cultured precardiac mesoderm cells explanted
      from stage 6 embryos. Similar to the effects of anterior endoderm, low
      concentrations of activin-A, FGF-2 (bFGF), or insulin significantly increased the
      incidence of explants that exhibited synchronous contractions and expressed
      cardiac alpha-actin mRNA. By contrast, explants treated with transferrin, bovine
      serum albumin, or nerve growth factor never contracted and contained only
      cytoplasmic beta-actin transcripts. These results provide additional evidence
      that endoderm-secreted activin-A, FGF-2, and perhaps insulin participate in
      regulating terminal cardiac differentiation in the embryo.

PMID- 7729589
TI  - Amino acid sequences of porcine Sp38 and proacrosin required for binding to the
      zona pellucida.
AB  - We previously purified a boar sperm protein, sp38, and demonstrated that this
      protein bound to the 90-kDa family of zona pellucida (ZP) glycoprotein in a
      calcium-dependent manner. Sp38 competed with proacrosin for the binding to the
      zona pellucida. Herein we have isolated cDNA clones encoding sp38 from a boar
      testis cDNA library in lambda gt11. The amino acid sequence deduced from the cDNA
      sequence indicated that sp38 is initially synthesized as a 350-residue precursor
      protein. The N-terminal 51-residue sequence preceded the N-terminus of the mature
      sp38. Thus, the sp38 precursor is post-translationally modified to produce the
      mature protein of 299 residues. Immunostaining of sperm cells using an antibody
      prepared against a fusion protein of sp38 with T7 gene 10 protein suggested that
      sp38 is localized at the intraacrosomal region and is released after the acrosome
      reaction. The 11-residue sequence, KRLSKAKNLIE, in sp38 shared a significant
      degree of similarity with the 8-residue sequence, KRLQQLIE, in the C-terminal
      region of porcine proacrosin. Both synthetic oligopeptides corresponding to these
      two sequences inhibited the binding of 125I-labeled sp38 to zona pellucida
      glycoprotein.

PMID- 7729590
TI  - Restoration of normal Hox code and branchial arch morphogenesis after extensive
      deletion of hindbrain neural crest.
AB  - Among the derivatives of the cephalic neural crest is the ectomesenchyme which
      subsequently constitutes most of the craniofacial skeleton. There is evidence to
      suggest that the skeletogenic fate of the hindbrain neural crest is specified
      before emigration from the neural tube and that Antennapedia class Hox genes are
      involved in that process. To explore the putative causal link between Hox
      expression and craniofacial morphology, we produced a specific series of
      bilateral crest deletions in chick embryos and assessed branchial arch
      morphology, Hox gene expression, and patterning of skeletal structures in the
      postoperative embryo. Surprisingly, we found that deletion of the bulk of the
      rhombencephalic crest and substantial portions of the dorsal rhombencephalon did
      not prevent normal branchial arch morphogenesis and normal patterns of Hox gene (
      A3 and -B4) expression 48 h after operation. Neural crest-like cells have been
      identified on crest migration pathways at the level of the original ablation,
      further confirming that ablated cephalic neural crest is replaced by regeneration
      from the cut edge of the neuroepithelium. Furthermore, in such embryos
      ectomesenchyme from regenerated crest is able to form a facial skeleton in which
      the mandible and hyoid apparatus are normal in size and organization. These
      findings demonstrate that the cranial neuroepithelium has more extensive
      regenerative capacities than was previously thought, which has important
      implications for investigations of craniofacial development.

PMID- 7729591
TI  - Developmental regulation of the alpha-methyldopa hypersensitive gene of
      Drosophila melanogaster.
AB  - The insect cuticle is a highly differentiated structure exhibiting considerable
      variety and specialization. Part of this specialization is achieved by regulating
      the nature and/or extent of sclerotization. The dopa decarboxylase (Ddc) and
      alpha-methyldopa hypersensitive (l(2)amd) genes of Drosophila are structurally
      related and it has been shown that the Ddc gene is required for the proper
      sclerotization of pigmented cuticle as well as for neurotransmitter production.
      The physiological role of the amd gene is unknown. Following the pattern of amd
      expression during development, we find that it is expressed in tissues that
      secrete clear flexible (arthrodial) cuticle both internally and in specialized
      external structures. We present electron microscopic evidence that loss of amd
      function leads to cuticle defects in a region of amd expression. We also find
      that amd is expressed in the larval CNS and ring gland where it may be involved
      in neurotransmitter metabolism similar to its paralog, Ddc. Lymph glands also
      express amd suggesting a possible role in the immune response. The expression of
      amd in segmentally repeating stripes at the end of dorsal closure suggests that
      amd may be a terminal target of the segmentation gene hierarchy which specifies
      segments.

PMID- 7729592
TI  - Molecular and genetic analysis of the Drosophila mas-1 (mannosidase-1) gene which
      encodes a glycoprotein processing alpha 1,2-mannosidase.
AB  - Glycosylation is an important mechanism for modulating the physicochemical and
      biological properties of proteins in a stage- and tissue-specific manner. The
      enzymology of this process is just beginning to be understood. Here we present
      the molecular analysis of mas-1 (mannosidase-1), a Drosophila gene with
      significant homologies to mammalian and Saccharomyces cerevisiae glycoprotein
      processing alpha 1,2-mannosidases. An enhancer-trap P-element inserted upstream
      of mas-1 leads to highly specific lacZ expression in the lobula plate giant
      neurons, cells that mediate the large-field optomotor response. This staining,
      however, seems to reflect only a small part of the complex expression pattern of
      the mas-1 gene: Two promoters produce alternative transcripts that show
      individual spatial distributions during embryonic development, including a
      maternal contribution. Both transcripts code for type II transmembrane proteins
      which differ in their N-terminal parts. Null mutants in mas-1 display defects in
      the embryonic PNS, in the wing, and in the adult eye. These findings illustrate
      that the processing of N-linked glycans plays a functional role in Drosophila
      development. There is, however, ample evidence for genetic and biochemical
      redundancy in the mannose-trimming steps of this pathway.

PMID- 7729593
TI  - Association of p34cdc2 and cyclin B1 during meiotic maturation in porcine
      oocytes.
AB  - The relative levels and association of p34cdc2 and cyclin B1 have been determined
      in pig oocytes during meiotic progression from G2 to metaphase II (MII). Fully
      grown G2-arrested porcine oocytes contained large amounts of free p34cdc2 and
      extremely small amounts of p34cdc2-cyclin B1 complex which did not increase in
      amount during the GV stage. Cyclin B1 is not synthesized in measurable quantities
      until 23 hr after the start of maturation. During the first metaphase (MI) the
      amount of both cyclin B1 and the p34cdc2-cyclin B1 complex increased sharply
      until 35 hr. Thereafter the amount of the p34cdc2-cyclin B1 complex increased
      again to 45 hr, resulting in higher levels of the complex in MII than in MI.
      Moreover, three distinct migration forms of p34cdc2 were detected in pig oocytes
      by immunoblotting with anti-PSTAIRE antibody, and most of the cyclin B1
      associated p34cdc2 was detected in the lower band in MI oocytes but migrated in
      the second band during MII. These results suggest that cyclin B1 levels in
      porcine oocytes differ from those in starfish, clam, and Xenopus oocytes in which
      considerably higher concentrations of cyclin B1 appear to be present during the
      GV stage and that the nature of the association between p34cdc2 and cyclin B1
      changes between the first and the second metaphase.

PMID- 7729594
TI  - Increased proteolytic activity of the granule neurons may contribute to neuronal
      death in the weaver mouse cerebellum.
AB  - The weaver mouse mutation is a genetic defect of unknown origin that leads to
      impairment of cerebellar granule neuronal migration and to neuronal cell death.
      We investigated laminin expression and proteolytic enzyme activity in this
      migration-deficient mouse mutant in vivo and in vitro to search for a molecular
      basis for the weaver defect. The weaver cerebellum showed a general increase in
      immunoreactivity for laminin, for a neurite outgrowth domain of the B2 chain of
      laminin, and for tissue plasminogen activator compared to the normal animals.
      Zymographic assays and immunocytochemistry confirmed that tissue plasminogen
      activator was the proteolytic enzyme synthesized in excess in the weaver mouse
      cerebellum in vivo. When placed in culture, the weaver granule neurons survived
      poorly on a laminin substratum, and failed to extend long neurites, unlike the
      normal cerebellar granule neurons. The cultured weaver granule neurons were
      proteolytically overactive and secreted excessive amounts of tissue plasminogen
      activator, which was likely to interfere with their neurite outgrowth potential
      on a laminin substratum. Indeed, the weaver granule neurons but not the normal
      neurons degraded laminin from their culture substratum and deposited a neurite
      outgrowth domain of the B2 chain of laminin onto their surfaces.
      Electrophysiology showed that the weaver granule neurons had poor resting
      membrane potentials (-38 V), whereas the normal neurons had normal resting
      membrane potentials of (-61 V). The resting membrane potentials of the weaver
      granule neurons were restored to near normal (-59 V) by a protease inhibitor,
      aprotinin. Aprotinin also rescued the weaver granule neurons from death on a
      laminin substratum and promoted their neurite outgrowth to the level of the
      normal animals. These results indicate that increased proteolytic activity
      accompanied with increased synthesis of laminin, and its B2 chain, distinguish
      the weaver mutation from the normal animals. These molecular changes may
      contribute to the impairment of granule neuronal migration and to the neuronal
      death, characteristic of the weaver mutation.

PMID- 7729595
TI  - Changes in connexin expression and distribution during chick lens development.
AB  - Gap junctions are composed of the connexins, a family of proteins which have been
      shown to be the structural and functional building blocks of gap junctional
      intercellular channels. In the chick lens, three members of the connexin (Cx)
      family have been characterized: Cx 43 has been shown to be a component of
      interepithelial cell gap junctions, and Cx 45.6 and Cx 56 have been shown to be
      part of fiber-to-fiber junctions. Early in chick development, gap junctional
      communication between differentiating lens fibers in the chick loses its
      sensitivity to blockade by elevated carbon dioxide (CO2). The lens epithelial
      cells, however, remain CO2-sensitive throughout development. A possible
      explanation for the change in CO2 sensitivity is that the lens fibers express
      differentiation-specific connexins with different physiological properties. Using
      specific antibodies for each of the three lens connexins, we show here that the
      lens fibers began to express Cx 45.6, and Cx 56 at the developmental stage when
      lens fibers acquired CO2-insensitivity. However, electron microscopic
      immunocytochemistry revealed that both Cx 45.6 and Cx 56 were found in
      interepithelial cell gap junctions, in addition to Cx 43. Conductances between
      paired Xenopus oocytes injected with Cx 43, Cx 45.6 and Cx 56 mRNAs revealed that
      all three connexins were CO2-sensitive in this expression system. Taken together,
      these data ruled out the possibility that the change in CO2 sensitivity observed
      in vivo could be explained on the basis of the distribution of connexins alone;
      other parameters of cellular context, such as post-translational processing, must
      be involved in the observed developmental changes in physiology.

PMID- 7729596
TI  - Agrin gene expression in ciliary ganglion neurons following preganglionic
      denervation and postganglionic axotomy.
AB  - Agrin is an extracellular matrix protein that has been implicated as a
      synaptogenic agent in the peripheral and central nervous systems. Both the level
      of expression and pattern of alternative splicing of agrin mRNA are
      developmentally regulated. As a step toward identifying signals important in
      regulating agrin gene expression in neurons, we examined the effects of
      postganglionic axotomy or preganglionic denervation on agrin mRNA levels and
      alternative splicing in ciliary ganglia of posthatch chicks. In comparison to
      unoperated age-matched controls, in situ hybridization with a pan-specific agrin
      cRNA probe demonstrated a significant decrease in neuronal agrin mRNA expression
      as a result of axotomy. Reverse transcription-polymerase chain reaction analysis
      demonstrated that axotomy also resulted in changes in the pattern of alternative
      splicing of agrin mRNA. Underlying these changes are decreases in the molar
      amounts of transcripts encoding the neuron-specific isoforms agrin8 and agrin19,
      homologous to rat agrin proteins that have high AChR aggregating activity.
      Similar, but less dramatic changes in agrin expression following axotomy were
      also observed in unoperated neurons on the contralateral side. In contrast, the
      only significant change in agrin gene expression following ganglionic denervation
      was a small decline in the relative abundance of agrin 8 mRNA in operated versus
      unoperated age-matched control ganglia. Major changes in agrin gene expression
      following axotomy but not denervation are consistant with the notion that agrin
      synthesized by ganglionic neurons exerts its effects in the periphery rather than
      at synapses formed between ciliary ganglion neurons and their preganglionic
      input. These data suggest that the pattern of alternative splicing and the
      absolute amount of agrin mRNA in ciliary ganglion neurons may be regulated by
      target tissue interactions.

PMID- 7729598
TI  - Induction of Xenopus oocyte meiotic maturation by MAP kinase.
AB  - Mitogen-activated protein kinase (MAPK) is one of the protein kinases activated
      during meiotic maturation of Xenopus laevis oocytes. The c-Mosxe protein kinase,
      which has been shown to be sufficient to promote germinal vesicle breakdown
      (GVBD) in meiosis I, can directly activate MAP kinase kinase in vitro and leads
      to the activation of MAPK in vivo. Recently we have shown that constitutively
      activated MAPK induces metaphase arrest when injected into one blastomere of a
      two-cell embryo. This arrest mimics the natural arrest of vertebrate unfertilized
      eggs in second meiotic metaphase due to cytostatic factor and c-Mosxe activity.
      We show here that microinjection of constitutively activated thiophosphorylated
      MAPK into resting oocytes is able to activate maturation-promoting factor (MPF)
      and promote GVBD. These results strongly support the hypothesis that MAPK plays
      an important role in the pathway that links c-Mosxe to the activation of MPF.

PMID- 7729597
TI  - Stage-specific induction and regulation by genomic imprinting of the mouse U2afbp
      rs gene during preimplantation development.
AB  - The mouse U2afbp-rs gene is imprinted and expressed exclusively from the paternal
      allele in the adult. To determine whether the U2afbp-rs gene is regulated by
      imprinting in the early embryo and to examine its normal temporal pattern of
      expression, we used a new quantitative RT-PCR approach to compare U2afbp-rs gene
      expression between androgenetic and gynogenetic embryos and to monitor U2afbp-rs
      expression during normal preimplantation embryogenesis. The U2afbp-rs gene is
      transcriptionally induced transiently at the 2-cell stage, making it one of the
      first genes ever identified with this pattern of regulation. At the 2-cell stage,
      androgenones express approximately twice as much U2afbp-rs mRNA as normal
      embryos, while gynogenones express much less. Thus, genomic imprinting regulates
      the U2afbp-rs gene from the time of its initial induction, distinguishing it from
      some other autosomal imprinted genes that have been analyzed (e.g., Igf2r and
      Igf2). Because the function of the U2afbp-rs protein has not been determined, the
      significance of transient induction of the U2afbp-rs gene at the 2-cell stage is
      not clear. Our data indicate that abundant expression of the U2afbp-rs gene is
      not essential for early development since gynogenones form blastocysts at a high
      frequency.

PMID- 7729599
TI  - Retinoic acid is a potent growth activator of mouse primordial germ cells in
      vitro.
AB  - Effects of retinoic acid (RA) on the growth of mouse primordial germ cells (PGC)
      were studied using an in vitro coculture system. Addition of RA to the culture
      medium markedly increased the number of PGC of the migratory phase and also
      significantly retarded the depletion of gonadal PGC. We observed stimulation of
      mitotic activity by RA treatment at all stages of PGC examined (8.5, 11.5, and
      13.5 days postcoitum), even in the absence of feeder cells. From these results,
      we conclude that RA affects PGC directly to promote their survival and
      proliferation and that the RA-induced intracellular signal may have a crucial
      role in the development of PGC.

PMID- 7729600
TI  - Tissue- and developmental stage-specific imprinting of the mouse proinsulin gene,
      Ins2.
AB  - We have investigated the imprinting status of two insulin genes using an
      interspecific recombinant congenic mouse strain carrying Ins1 and Ins2 alleles
      from Mus spretus on a C57BL/6 genetic background. At Days 12.5, 13.5, and 14.5 of
      gestation, expression of both parental alleles of both Ins1 and Ins2 was detected
      in the bodies of the embryos. In the heads, only Ins2 expression was detected,
      and, again, both parental alleles were expressed. In yolk sacs, only Ins2
      transcripts were found. Both parental alleles were expressed on Day 12.5, but the
      expression of the maternal allele gradually declined with only the paternal
      allele remaining active by Day 14.5. Thus, Ins2 is subject to genomic imprinting
      in the yolk sac. This imprinting is not only tissue-specific, but appears to be a
      multistep process with postzygotic events likely to play an important role in
      repression of the maternal allele.

PMID- 7729601
TI  - Mammalian CD2 is an effective heterologous marker of the cell surface in
      Drosophila.
AB  - Ectopic expression of neutral proteins, such as beta-galactosidase, in developing
      embryos has been an invaluable tool for studies of gene expression and embryonic
      development. However, expression of beta-galactosidase does not reveal the shape
      of the cells containing it. We have examined the suitability of rat CD2, a small
      transmembrane protein of the immunoglobulin superfamily, as a marker of cell
      morphology in Drosophila. We selected the regulatory sequences of the Drosophila
      mesoderm-specific gene twist to express CD2 and prepared a chimeric gene, twi
      CD2. Embryos containing twi-CD2 faithfully express CD2 in the same pattern as
      Twist. Expression of CD2 on the surface of cells reveals the shape of cells when
      stained with existing monoclonal antibodies. We have also constructed a CD2 gene
      that can be used with the GAL4 system and show that CD2 can be expressed on the
      surface of epithelial cells and along the length of axons.

PMID- 7729602
TI  - A Drosophila E(spl) gene is "neurogenic" in Xenopus: a green fluorescent protein
      study.
AB  - A Drosophila Enhancer of split [E(spl)] bHLH protein, m delta, was misexpressed
      in Xenopus embryos along with green fluorescent protein (GFP) as a lineage label.
      The Drosophila protein translocated to the nucleus of Xenopus cells and led to
      neural hypertrophy in the GFP-labeled dorsal ectoderm, a phenotype similar to
      that caused by the misexpression of activated Xotch. Our data indicate a strong
      conservation in E(spl)bHLH function in the Notch signaling pathway of flies and
      vertebrates.

PMID- 7729603
TI  - Preventing non-insulin-dependent diabetes.
AB  - Many risk factors for non-insulin-dependent diabetes mellitus (NIDDM), such as
      obesity, physical inactivity, and high-fat diet, can potentially be modified.
      Furthermore, some of the metabolic abnormalities, such as insulin resistance and
      impaired glucose tolerance, that predict diabetes can be improved by behavior
      modification and drug treatment. Thus, at least to some extent, NIDDM may be
      preventable. Several small clinical trials have addressed the hypothesis that
      NIDDM can be prevented by dietary modification, physical activity, or drug
      treatment. Some studies suggest a preventive effect, but the conclusions are
      limited by considerations of sample size, randomization, or intensity of the
      interventions. Consequently, the hypothesis that NIDDM is preventable requires
      further testing.

PMID- 7729604
TI  - Lack of relationship between an insertion/deletion polymorphism in the
      angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative
      retinopathy in IDDM patients.
AB  - Genotypic abnormalities of the renin-angiotensin system have been suggested as a
      risk factor for the development of diabetic nephropathy and proliferative
      retinopathy. We studied the relationship between an insertion(I)/deletion (D)
      polymorphism in the angiotensin-converting enzyme (ACE) gene in insulin-dependent
      diabetes mellitus (IDDM) patients with diabetic nephropathy (121 men and 77
      women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years) and in IDDM
      patients with normoalbuminuria (118 men and 74 women, age 42.7 +/- 10 years,
      diabetes duration 26 +/- 8 years). A total of 155 patients (40%) had
      proliferative retinopathy, and 67 patients (17%) had no diabetic retinopathy.
      There was no difference in genotype distribution between IDDM patients with
      diabetic nephropathy and those with normalbuminuria: 63 (32%)/95 (48%)/40 (20%)
      vs. 67 (35%)/77 (41%)/46 (24%) had DD/ID/II genotypes, respectively. Patients
      with nephropathy had higher plasma ACE levels (609 [151-1,504] micrograms/l)
      compared with patients with normoalbuminuria (428 [55-1,630] micrograms/l) (P <
      0.001). Multiple linear regression analysis revealed that the plasma ACE level in
      patients with nephropathy is partially determined by ACE/ID polymorphism, mean
      arterial blood pressure, and glomerular filtration rate (r2 = 0.30, P < 0.001).
      There was no difference in genotype distribution between IDDM patients with
      proliferative retinopathy and those without diabetic retinopathy: 52 (34%)/74
      (48%)/29 (19%) vs. 26 (39%)/25 (37%)/16 (24%) had DD/ID/II genotypes,
      respectively. There was also no difference in plasma ACE concentration detected
      among patients with no, simplex, or proliferative retinopathy.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7729605
TI  - Altered glucose dependence of glucagon-like peptide I(7-36)-induced insulin
      secretion from the Zucker (fa/fa) rat pancreas.
AB  - In previous studies on the enteroinsular axis in Zucker rats, it was found that
      glucose-dependent insulinotropic polypeptide (GIP) levels were normal in obese
      animals, but the glucose threshold for the insulinotropic action of GIP in the
      perfused rat pancreas was reduced. Glucagon-like peptide I (GLP-I)(7-36) is also
      an important incretin, and in the current study, glucose, insulin, and
      immunoreactive (IR)-COOH-terminal GLP-I responses to oral glucose were compared
      in lean (Fa/?) and obese (fa/fa) rats. In addition, the concentration thresholds
      for stimulation and glucose dependence of perfused pancreases to GLP-I(7-36) were
      examined. Glucose responses to oral glucose were similar in fa/fa and Fa/? rats.
      Obese animals were hyperinsulinemic when fasting and after oral glucose.
      Significant increases in IR-GLP-I levels in response to glucose were only
      observed in fa/fa rats. Perfused pancreases from fa/fa rats hypersecreted insulin
      at all glucose concentrations. In the presence of 4.4 mmol/l glucose, GLP-I(7-36)
      increased insulin secretion in fa/fa pancreases approximately 25-fold, whereas
      there was only a 5-fold increase in Fa/? pancreases. Pancreases from fa/fa rats,
      perfused with a glucose gradient (2.8-11 mmol/l) in the presence of GLP-I(7-36),
      responded with an immediate increase in insulin secretion, i.e., at a glucose
      concentration of 2.8 mmol/l, whereas Fa/? pancreases required a minimum of 4.22
      mmol/l glucose for stimulation. With high glucose (16.7 mmol/l), both fa/fa and
      Fa/? rat pancreases exhibited similar responsiveness to GLP-I(7-36), having
      thresholds of < 50 pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729606
TI  - Decreased interstitial apolipoprotein A-I levels in IDDM patients with diabetic
      nephropathy.
AB  - The risk of cardiovascular morbidity and mortality is highly increased in
      patients with diabetic nephropathy. Postulating that the generalized vasculopathy
      observed in these patients may enhance transcapillary filtration of lipids and
      lipoproteins resulting in a more atherogenic interstitial lipid profile, we set
      out to analyze the composition of their interstitial fluid. We studied healthy
      control subjects (n = 9), normoalbuminuric insulin-dependent diabetes mellitus
      (IDDM) patients (n = 16), and IDDM patients with diabetic nephropathy (n = 11)
      matched for age, body mass index, smoking habits, duration of diabetes, and
      metabolic control. Interstitial fluid was collected after an overnight fast by
      applying mild suction (200 mmHg) to the skin. Interstitial apolipoprotein A-I
      (apoA-I) levels were significantly lower in patients with nephropathy (0.18 +/-
      0.10 milligram [mean +/- SD]) compared with normoalbuminuric diabetic patients
      (0.29 +/- 0.08 milligram) and healthy control subjects (0.30 +/- 0.09 milligram).
      Interstitial apolipoprotein B:apoA-I ratios tended to be higher in patients with
      diabetic nephropathy. In these patients, normal interstitial low-density
      lipoprotein cholesterol concentrations were observed in the presence of lower
      apoA-I levels. Transcapillary filtration of apoA-I was significantly lower in
      patients with diabetic nephropathy. Furthermore, an altered multiple regression
      model explaining interstitial apoA-I levels was observed in diabetic nephropathy.
      In this model, transcapillary protein (IgG) filtration and serum apoA-I levels no
      longer explained interstitial apoA-I levels. If we assume that interstitial apoA
      I is involved in reverse cholesterol transport, these data suggest a more
      atherogenic interstitial lipoprotein profile in IDDM patients with nephropathy.

PMID- 7729607
TI  - Defects in insulin secretion and action in women with a history of gestational
      diabetes.
AB  - Gestational diabetes mellitus (GDM) is associated with defects in insulin
      secretion and insulin action, and women with a history of GDM carry a high risk
      for the development of non-insulin-dependent diabetes mellitus (NIDDM).
      Assessment of subjects with a history of GDM who are currently normoglycemic
      should help elucidate some of the underlying defects in insulin secretion or
      action in the evolution of NIDDM. We have studied 14 women with normal oral
      glucose tolerance who had a history of GDM. They were compared with a group of
      control subjects who were matched for both body mass index (BMI) and waist-to-hip
      ratio (WHR). All subjects underwent tests for the determination of oral glucose
      tolerance, ultradian oscillations in insulin secretion during a 28-h glucose
      infusion, insulin secretion in response to intravenous glucose, glucose
      disappearance after intravenous glucose (Kg), and insulin sensitivity (SI) as
      measured by the Bergman minimal model method. The BMI in the post-GDM women was
      similar to that in the control subjects (24.9 +/- 1.2 vs. 25.4 +/- 1.4 kg/m2,
      respectively), as was the WHR ratio (0.80 +/- 0.01 vs. 0.76 +/- 0.01,
      respectively). The post-GDM women were slightly older (35.2 +/- 0.9 vs. 32.1 +/-
      1.4 years, P = 0.04). The fasting plasma glucose levels were significantly higher
      in the post-GDM group than in the control group (4.9 +/- 0.1 vs. 4.4 +/- 0.1
      mmol/l, respectively, P < 0.001) and remained higher at each of the subsequent
      determinations during the oral glucose tolerance test, although none had a result
      indicative of either diabetes or impaired glucose tolerance.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7729608
TI  - Effects of recent, short-term hyperglycemia on responses to hypoglycemia in
      humans. Relevance to the pathogenesis of hypoglycemia unawareness and
      hyperglycemia-induced insulin resistance.
AB  - A single episode of recent hypoglycemia increases, whereas long-term
      hyperglycemia decreases, the glycemic thresholds of responses of
      counterregulatory hormone and symptoms to subsequent hypoglycemia in humans. To
      assess whether short-term, antecedent hyperglycemia exerts effects opposite to
      those observed after acute hypoglycemia, seven normal, nondiabetic subjects and
      eight insulin-dependent diabetes mellitus (IDDM) patients were studied during
      hyperinsulinemic-hypoglycemic clamp (sequential, 90-min plateaus of plasma
      glucose [PG] of 4.3, 3.7, 3.0, and 2.4 mmol/l). Nondiabetic subjects were studied
      the morning after either 6-h clamped hyperglycemia (PG approximately 13.5 mmol/l)
      or euglycemia (PG approximately 5 mmol/l) between 1600 and 2200 the previous day
      (glucose and insulin infused on both occasions), as well as after nocturnal
      hyperglycemia (PG approximately 13.5 mmol/l) or euglycemia between 2300 and 0500.
      The IDDM patients were studied after 15 h of euglycemia or hyperglycemia
      (approximately 17 mmol/l) but identical hyperinsulinemia (approximately 225
      pmol/l) between 1600 and 0700. Neither PG thresholds of counterregulatory
      hormone, symptoms, onset of cognitive dysfunction to hypoglycemia, nor maximal
      responses were affected by antecedent, short-term hyperglycemia in normal
      nondiabetic subjects and IDDM patients (NS). However, the rate of glucose
      infusion required to maintain hypoglycemic plateaus during hypoglycemia was lower
      after hyperglycemia (nondiabetic subjects 31.2 +/- 3.4 vs. 36.7 +/- 4 mumol.kg
      1.min-1, IDDM patients 33 +/- 3.1 vs. 42.5 +/- 3.9 mumol.kg-1.min-1; P < 0.05)
      indicating greater insulin resistance induced by antecedent hyperglycemia. In
      conclusion, in contrast to acute hypoglycemia and long-term hyperglycemia,
      recent, short-term hyperglycemia does not affect physiological responses to
      hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729609
TI  - Impaired activation of glucose oxidation and NADPH supply in human endothelial
      cells exposed to H2O2 in high-glucose medium.
AB  - The effects of glucose concentration on D-glucose oxidation and reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) supply were studied during
      exposure of cultured human umbilical vein endothelial cells to hydrogen peroxide
      (H2O2). The activation of glucose oxidation via the pentose phosphate pathway
      (PPP), induced by exposure of cells to 200 mumol/l H2O2 for 1 h, was reduced by
      50% (P < 0.01) in cells cultured for 5-7 days in 33 mmol/l D-glucose (HG) versus
      those cultured in 5.5 mmol/l D-glucose without (NG) or with (HR) 27.5 mmol/l D
      raffinose. The intracellular NADPH content in HG cells, but not in NG or HR
      cells, was decreased by 42% (P < 0.01) by exposing cells to 200 mumol/l H2O2. The
      decrease in NADPH was dependent on D-glucose concentration in the medium and was
      prevented in glutathione (GSH)-depleted cells. The latter observation suggests
      that the decrease in NADPH is associated with activation of the GSH redox cycle.
      In the presence of 200 mumol/l H2O2, lactate release into the medium, NADH/NAD
      ratio, and phosphofructokinase activity in HG cells were 56, 53, and 68% greater,
      respectively, than in the NG group, which indicates that inhibition of glycolysis
      by H2O2 is less marked in the HG group compared with NG group. These results
      indicate that activation of the PPP was impaired in endothelial cells cultured
      under conditions of high-glucose and oxidative stress, resulting in a decreased
      supply of NADPH to various NADPH-dependent pathways, including the GSH redox
      cycle.

PMID- 7729610
TI  - DRB1*0403 protects against IDDM in Caucasians with the high-risk heterozygous
      DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype. Belgian Diabetes Registry.
AB  - The human leukocyte antigen (HLA) class II genotype DQA1*0301-DQB1*0302/DQA1*0501
      DQB1*0201 has been identified as a marker strongly predisposing to insulin
      dependent diabetes mellitus (IDDM) in Caucasian populations. Its frequency in
      control populations (1-3%) is still, however, 1 order of magnitude higher than
      the prevalence of IDDM, suggesting that its penetrance can be modified by
      protective factors. In this study we searched for such a factor in the DRB1 locus
      by studying DRB1*04 polymorphism in 174 European Caucasian IDDM patients and 73
      nondiabetic control subjects, all sharing the HLA-DR3/DR4 phenotype. Significant
      protection was encoded by the DRB1*0403 allele, which was observed in 5 of 49
      control subjects (10%) and none of 171 IDDM patients (0%) with the DQA1*0301
      DQB1*0302/DQA1*0501-DQB1*0201 genotype (RR = 0.02 [0.01-0.18], P < 0.0005). These
      data support the concept that protective HLA class II genes can overrule the risk
      caused by HLA-DQ susceptibility dimers. They also contribute to a possible
      strategy to screen for nondiabetic individuals with increased genetic risk of
      developing IDDM.

PMID- 7729611
TI  - Possible role for TNF-alpha in early embryopathy associated with maternal
      diabetes in the rat.
AB  - Tumor necrosis factor (TNF) bioactivity was assessed in culture media conditioned
      with uterine cells collected from control or diabetic rats on days 5 and 8 of
      pregnancy. On both days, diabetic uterine cells released significantly more
      biologically active TNF than did control cells, and this activity was
      significantly decreased by the addition of anti-TNF-alpha antibodies but not by
      the addition of normal IgG when WEHI 164 cells were used as a target. When
      uterine tissues from day 5 or day 8 pregnant diabetic rats were tested by
      Northern blot analysis, TNF-alpha mRNAs were twofold more abundant than in
      control samples, but the difference was not statistically significant (P = 0.086
      and 0.100, respectively). Immunohistochemical analysis of diabetic day 5 uterine
      sections revealed that most of the TNF-alpha synthesis occurs in the epithelium
      lining the uterine lumen. Finally, the growth of day-5 embryos in culture medium
      conditioned with day-5 diabetic uterine cells was significantly reduced when
      compared with that of embryos in medium conditioned with control cells. Embryonic
      development was markedly improved when anti-TNF-alpha antibodies were added to
      the diabetic-cell conditioned medium. Our data support the hypothesis that TNF
      alpha may be implicated in the developmental deficiencies observed in
      preimplantation embryos from pregnant diabetic rats.

PMID- 7729612
TI  - Myocardial glucose uptake evaluated by positron emission tomography and
      fluorodeoxyglucose during hyperglycemic clamp in IDDM patients. Role of free
      fatty acid and insulin levels.
AB  - Myocardial and whole-body glucose metabolism was assessed in 19 insulin-dependent
      diabetes mellitus (IDDM) patients. A hyperglycemic clamp was performed 1) in the
      absence of insulin at free fatty acid (FFA) levels of 1.0 mmol/l (test 1); 2) in
      the absence of insulin at low FFA levels (0.1 mmol/l) by means of a lipid
      lowering drug, acipimox (test 2); 3) during insulin infusion to achieve systemic
      levels of 400 pmol/l and FFA levels of 0.1 mmol/l (test 3); and 4) at the insulin
      levels of test 3 but increasing FFA to 1.0 mmol/l by means of heparin and
      intralipid infusion (test 4). Myocardial glucose uptake was measured by positron
      emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose. Whole-body glucose
      uptake was measured in the four conditions by the glucose infusion rate during
      the PET scanning period. Myocardial glucose uptakes were 40.3 +/- 18.0, 395.5 +/-
      139.6, 852.2 +/- 99.1, and 1,388.4 +/- 199.1 mumol.kg tissue-1.min-1 (mean +/-
      SD) and whole-body glucose uptakes were 10.1 +/- 2.3, 10.1 +/- 3.4, 42.8 +/- 5.8,
      and 30.5 +/- 5.6 mumol.kg body wt-1.min-1 during tests 1, 2, 3, and 4,
      respectively. Thus, in IDDM patients without coronary artery disease under the
      condition of hyperglycemia, an increase of myocardial glucose uptake was obtained
      either by lowering of FFA levels during hypoinsulinemia or by an increase in FFA
      levels during hyperinsulinemia. In both conditions no significant changes of
      whole-body glucose uptake were demonstrated.

PMID- 7729613
TI  - Myocardial m-[123I]iodobenzylguanidine scintigraphy for the assessment of
      adrenergic cardiac innervation in patients with IDDM. Comparison with
      cardiovascular reflex tests and relationship to left ventricular function.
AB  - Cardiac imaging using m-[123I]iodobenzylguanidine (mIBG) reflects sympathetic
      myocardial innervation. In patients with insulin-dependent diabetes mellitus
      (IDDM), the following were studied: 1) the prevalence of derangements of cardiac
      autonomic innervation as detected by mIBG scintigraphy in comparison with
      cardiovascular reflex tests and 2) the relationship between adrenergic cardiac
      innervation and left ventricular (LV) function. Twenty-four patients with IDDM
      without overt heart disease were studied after silent coronary artery disease was
      excluded by 201Tl scintigraphy. Cardiac innervation was evaluated by both mIBG
      scintigraphy (tomographic imaging) and cardiovascular reflex tests. Systolic
      (ejection fraction [EF] percentage) and diastolic (peak filling rate [PFR]
      defined as end-diastolic volumes per second [EDV/s]) LV function were determined
      by equilibrium radionuclide angiography at rest and during bicycle exercise. mIBG
      scintigraphy was also performed in 10 control subjects. All control subjects
      exhibited a normal myocardial mIBG distribution. Among diabetic patients, only
      six had normal mIBG scans (group 1), whereas 18 had evidence of regional
      adrenergic denervation (group 2). Reflex tests suggested cardiac autonomic
      neuropathy in only seven of these patients (P < 0.01 vs. mIBG). All patients had
      a normal EF at rest. However, group 2 showed an impaired response to exercise as
      indicated by a smaller increase in EF (5 +/- 6 vs. 13 +/- 5%, P < 0.05) and a
      lower PFR (5.9 +/- 0.8 vs. 7.3 +/- 1.2 EDV/s, P < 0.01). Myocardial mIBG
      scintigraphy reveals that in patients with IDDM, sympathetic myocardial
      dysinnervation is much more common than previously thought. Furthermore,
      subclinical LV dysfunction is related to derangements of adrenergic cardiac
      innervation.

PMID- 7729614
TI  - Islet-infiltrating lymphocytes from prediabetic NOD mice rapidly transfer
      diabetes to NOD-scid/scid mice.
AB  - In an effort to study the development of diabetes in NOD mice, our laboratory
      developed a novel adoptive transfer model using NOD-scid/scid (NOD-scid) mice as
      recipients of islet-infiltrating lymphocytes from donor prediabetic female NOD
      mice. We first confirmed previous results that demonstrated that splenocytes of
      diabetic and prediabetic female NOD mice could transfer diabetes to NOD-scid
      mice. We demonstrated that the kinetics of disease transfer were dependent on the
      age of transferred lymphocytes and reiterated the kinetics of diabetes in
      conventional female NOD mice. We then demonstrated that islet-infiltrating
      lymphocytes from prediabetic female NOD mice could transfer diabetes. In contrast
      with the age-dependent transfer of diabetes seen using splenocytes, islet
      infiltrating lymphocytes obtained from prediabetic female NOD mice aged > or = 40
      days rapidly transferred diabetes to NOD-scid recipients. The time required to
      transfer insulin-dependent diabetes mellitus (IDDM) using islet-infiltrating
      lymphocytes from young prediabetic mice (25 +/- 9 days) was not statistically
      different from the time required to transfer IDDM using splenocytes from overtly
      diabetic mice (32 +/- 5 days). Cotransfer of splenocyte cells or CD4+, but not
      CD8+ spleen cells, from 60- to 80-day-old prediabetic female NOD mice together
      with either splenocytes from diabetic mice or islet-infiltrating lymphocytes from
      prediabetic NOD mice delayed the rapid transfer of IDDM, suggesting that CD4+
      cells mediated immunoregulation. Use of the NOD-scid islet-infiltrating
      lymphocyte-adoptive transfer model should help elucidate the pathophysiology of
      the early inflammatory events leading to insulitis and subsequent beta-cell
      destruction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729615
TI  - Skeletal muscle GLUT4 protein concentration and aging in humans.
AB  - The insulin resistance of aging has been attributed to a postreceptor defect in
      skeletal muscle. The present study examined whether a reduction in the
      concentration of the insulin-stimulated glucose transporter (GLUT4) in skeletal
      muscle was associated with advancing age in men (n = 55) and women (n = 29).
      Insulin sensitivity (minimal model) was negatively associated (P < 0.001) with
      age (range, 18-80 years) in men (r = -0.44) and women (r = -0.58). GLUT4 protein
      concentration in the vastus lateralis was also negatively associated (P < 0.05)
      with age (men, r = -0.28; women, r = -0.51). There was no relation (P > 0.15)
      between GLUT4 content in the gastrocnemius and age. GLUT4 concentration in the
      vastus lateralis was positively associated (P < 0.01) with insulin sensitivity in
      both sexes (r = 0.42); this relationship persisted in the men after adjusting for
      overall adiposity, regional adiposity, and cardiorespiratory fitness. These
      findings suggest that a decrement in GLUT4 protein concentration in skeletal
      muscle may at least partially contribute to the insulin resistance of aging in
      humans.

PMID- 7729616
TI  - Endothelial dysfunction precedes development of microalbuminuria in IDDM.
AB  - In patients with insulin-dependent diabetes mellitus (IDDM), microalbuminuria is
      a predictor of widespread severe microangiopathy and macroangiopathy. Patients
      with microalbuminuria show generalized dysfunction of the vascular endothelium,
      but it is unknown whether endothelial dysfunction precedes the development of
      microalbuminuria. We examined a cohort of 17 IDDM patients at baseline and on
      three occasions during a follow-up of (median) 64 months (range 51-89). All had
      normal (< 15 micrograms/min) urinary albumin excretion (UAE) at the first three
      examinations. At the fourth examination, 11 patients had normal UAE and 6 had
      microalbuminuria (median 25.7 micrograms/min [range 15.3-42.8]). Compared with
      patients with normal UAE, microalbuminuric patients had significantly higher
      plasma levels of von Willebrand factor (vWF), a marker of endothelial
      dysfunction, at the second (200% [168-274] vs. 131% [69-186]), third (208% [188
      270] vs. 125% [82-190]), and fourth examinations (231% [202-269] vs. 132% [88
      208], P < 0.0001), but not at baseline (128% [98-161] vs. 122% [87-210]). An
      increase in vWF preceded the occurrence of microalbuminuria by approximately 3
      years. The groups did not differ with regard to age, diabetes duration, blood
      pressure, mean glycated hemoglobin and cholesterol, smoking habits, or extent of
      retinopathy. Endothelial dysfunction, as estimated by plasma vWF concentration,
      precedes and may predict the development of microalbuminuria in IDDM.

PMID- 7729617
TI  - Role of the sympathoadrenal system in exercise-induced inhibition of insulin
      secretion. Effects of islet transplantation.
AB  - The present study was designed to investigate the mechanism leading to inhibition
      of insulin release during exercise. To investigate the influence of circulating
      epinephrine and norepinephrine, these catecholamines were infused intravenously
      in resting islet-transplanted and control rats. The role of neural influences on
      insulin release was investigated by a swimming exercise study in islet
      transplanted and control rats, before and after adrenodemedullation.
      Streptozotocin-induced diabetic Albino Oxford rats received 5 microliters islet
      tissue into the portal vein, resulting in return of normal basal glucose and
      insulin levels. Transplanted and control animals were provided with two permanent
      heart catheters to sample blood and to give infusions. Infusion of epinephrine
      and norepinephrine did not result in inhibition of plasma insulin levels. Blood
      glucose levels, as well as nonesterified fatty acids and insulin levels in
      plasma, were similar in both groups. After the infusion study, the animals were
      subjected to strenuous swimming. During exercise, plasma insulin levels decreased
      not only in controls, but also in the islet-transplanted group. Blood glucose and
      plasma catecholamine responses were identical in both groups. After
      adrenodemedullation, epinephrine was not detectable and the exercise-induced
      decrease of insulin was not affected. These results indicate that circulating
      epinephrine and norepinephrine in physiological concentrations do not cause
      inhibition of insulin secretion. Since the exercise-induced inhibition of insulin
      secretion is still present in rats with islet grafts, it seems reasonable to
      suggest that sympathetic neural influences are responsible for the inhibition of
      insulin release during exercise and that transplanted islets are sympathetically
      reinnervated.

PMID- 7729618
TI  - Levels of Tap-1 and Tap-2 mRNA and expression of Kd and Db on splenic lymphocytes
      are normal in NOD mice.
AB  - It has been reported that the level of Tap-1 (transporter associated with antigen
      processing) mRNA and the expression of class I on splenocytes are low in NOD
      mice. Class I expression at 37 degrees C depends on an adequate supply of
      peptides, so a decrease in Tap could lead to lower class I levels. Since
      hypoexpression of class I correlated uniformly with the development of diabetes,
      it has also been suggested that Tap-1nod is diabetogenic. However, others report
      normal Tap-1 and class I levels in NOD mice. We examined Tap-1 and Tap-2 mRNA
      levels in NOD/Smrf mice using a reverse transcriptase-polymerase chain reaction
      method that detects > or = 25% changes in mRNA. We also assessed class I
      expression with three monoclonal antibodies. No difference in Tap-1 or Tap-2 mRNA
      levels for females of different ages or between diabetic and nondiabetic animals
      was observed. Tap-1 mRNA levels were identical between NOD/Smrf and BALB/cJ mice.
      Kd expression was significantly lower on NOD lymphocytes than in BALB/cJ cells,
      but the difference was due to the smaller size of the NOD splenic lymphocyte.
      When cells of the same size were analyzed, no difference in class I levels was
      observed. Class I levels were also identical in diabetic and age-matched
      nondiabetic NOD and BALB/c females. Both NOD Tap-1 mRNA and class I were
      increased by interferon-gamma. We find no evidence for impaired NOD Tap gene
      activity or class I expression, as previously reported for this strain.

PMID- 7729619
TI  - Overexpression of apolipoprotein E prevents development of diabetic
      hyperlipidemia in transgenic mice.
AB  - To determine the role of apolipoprotein E (apoE) in diabetic hyperlipidemia, we
      induced diabetes in transgenic mice overexpressing apoE by intravenous injection
      of streptozotocin (STZ) and examined plasma lipoprotein metabolism in these mice.
      In STZ-induced diabetic mice, blood glucose levels were > 19 mmol/l (350 mg/dl)
      and plasma insulin levels were reduced to < 5 pmol/l (1 microU/ml). The diabetic
      nontransgenic mice developed hypercholesterolemia (plasma total cholesterol
      level: 4.55 +/- 1.32 vs. 1.97 +/- 0.13 mmol/l [176 +/- 51 vs. 76 +/- 5 mg/dl])
      and hypertriglyceridemia (plasma triglyceride level: 0.82 +/- 0.29 vx. 0.42 +/-
      0.11 mmol/l [73 +/- 26 vs. 37 +/- 10 mg/dl]) compared with values before
      induction of diabetes. In the diabetic nontransgenic mice, enhanced intestinal
      acylCoA:cholesterol acyltransferase activity was demonstrated, a factor that may
      contribute to the development of diabetic hyperlipidemia. Induction of apoE
      remarkably reduced the development of hyperlipidemia in diabetic transgenic mice
      compared with diabetic nontransgenic mice (plasma cholesterol level: 4.55 +/-
      1.32 vs. 3.31 +/- 0.47 mmol/l [176 +/- 51 vs. 128 +/- 18 mg/dl], P < 0.01, and
      plasma triglyceride level: 0.82 +/- 0.29 vs. 0.17 +/- 0.11 mmol/l [73 +/- 26 vs.
      15 +/- 10 mg/dl], P < 0.01). Plasma lipoprotein analysis by gel filtration
      chromatography showed that the reduction of plasma cholesterol and triglyceride
      levels was due to the disappearance of lipoproteins containing apoB. In these
      studies, we demonstrated the usefulness of STZ-induced diabetes in mice as an
      animal model for diabetic hyperlipidemia and demonstrated that endogenous
      induction of apoE in transgenic mice improved diabetic hyperlipidemia.

PMID- 7729620
TI  - Predicting future diabetes in Latino women with gestational diabetes. Utility of
      early postpartum glucose tolerance testing.
AB  - We tested 32 routine clinical parameters for their ability to discriminate
      between a high risk and a low risk of non-insulin-dependent diabetes mellitus
      (NIDDM) within 5-7 years after pregnancies complicated by gestational diabetes
      mellitus (GDM). Latino women (n = 671) with GDM who did not have diabetes 4-16
      weeks after delivery returned for at least one 75-g oral glucose tolerance test
      (OGTT) within 7.5 years. Multivariate analysis was used to identify parameters
      ascertained during or immediately after the index pregnancy that were
      independently associated with the development of diabetes during follow-up. Life
      table analysis revealed a 47% cumulative incidence rate of NIDDM 5 years after
      delivery for this cohort of patients who did not have diabetes at the initial
      postpartum examination. Four variables were identified as independent predictors
      of NIDDM: the area under the OGTT glucose curve at 4-16 weeks postpartum, the
      gestational age at the time of diagnosis of GDM, the area under the OGTT glucose
      curve during pregnancy, and the highest fasting serum glucose concentration
      during pregnancy. Examination of relative risks (RRs) of NIDDM between the
      highest and lowest quartiles of the cohort for each variable, adjusted for the
      other three variables, revealed that the postpartum OGTT provided the best
      discrimination between high-risk and low-risk individuals (adjusted RR = 11.5
      [95% confidence interval 4.5-29.1] compared with adjusted RRs of only 0.5-2.5 for
      the other three variables).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729621
TI  - Isolation of a cDNA clone encoding a KATP channel-like protein expressed in
      insulin-secreting cells, localization of the human gene to chromosome band
      21q22.1, and linkage studies with NIDDM.
AB  - The metabolism of glucose in insulin-secreting cells leads to closure of ATP
      sensitive K+ channels (KATP), an event that initiates the insulin secretory
      process. Defects in insulin secretion are a common feature of non-insulin
      dependent diabetes mellitus (NIDDM), and the beta-cell KATP that couples
      metabolism and membrane potential is a candidate for contributing to the
      development of this clinically and genetically heterogeneous disorder. We
      screened a hamster insulinoma cDNA library by low-stringency hybridization with a
      probe coding for the G-protein-coupled inwardly rectifying K+ channel GIRK1/KGA
      and isolated clones encoding a protein, KATP-2, whose sequence is 90% similar to
      that of the recently described KATP-1, an ATP-sensitive K+ channel expressed in
      heart and other tissues. RNA blotting showed that KATP mRNA was present in
      insulin-secreting cells and brain but not in heart. To assess the contribution of
      KATP-2 to the development of NIDDM, the human KATP-2 gene (symbol KCNJ7) was
      isolated and mapped to chromosome band 21q22.1 by fluorescence in situ
      hybridization. A simple tandem repeat DNA polymorphism, D21S1255, was identified
      in the region of the KATP-2 gene, and linkage studies between this marker and
      NIDDM were carried out in a group of Mexican-American sib pairs with NIDDM. There
      was no evidence for linkage between D21S1255 and NIDDM, indicating that KATP-2 is
      not a major susceptibility gene in this population.

PMID- 7729622
TI  - No evidence for mutations in a putative beta-cell ATP-sensitive K+ channel
      subunit in MODY, NIDDM, or GDM.
AB  - The beta-cell ATP-sensitive K+ (K-ATP) channel has a major role in glucose
      induced insulin secretion. Screening the entire coding sequence of the gene for a
      putative beta-cell K-ATP channel subunit, K-ATP2, with single-strand conformation
      polymorphism did not show any mutations associated with diabetes in white
      Caucasian diabetic patients, including five pedigrees with maturity onset
      diabetes of the young (MODY), 25 patients with noninsulin-dependent diabetes
      mellitus (NIDDM) selected for marked beta-cell deficiency, 25 selected for mild
      diabetes presenting before age 50 years with fasting plasma glucose levels < 10
      mmol/l, 25 unselected NIDDM patients, and 25 subjects with gestational diabetes
      mellitus (GDM) and subsequent raised fasting plasma glucose. In five large MODY
      pedigrees, linkage analysis with simple tandem-repeat polymorphisms (STRPs) near
      the K-ATP2 gene excluded linkage. In a population association study, no linkage
      disequilibrium for the STRP was found between 237 unselected white Caucasian
      NIDDM patients and 104 geographically matched and age-matched white Caucasian
      nondiabetic subjects. In addition, two silent polymorphisms were found with
      similar frequency in nondiabetic and diabetic subjects. Mutations in the gene for
      K-ATP2 are unlikely to be a major cause of MODY, NIDDM, or GDM.

PMID- 7729624
TI  - Too much bench, not enough bedside?

PMID- 7729623
TI  - Our new president--James W. Freston, M.D., Ph.D.

PMID- 7729625
TI  - Carbamylcholine- and catecholamine-induced intracellular calcium dynamics of
      epithelial cells in mouse ileal crypts.
AB  - BACKGROUND/AIMS: The intestinal epithelium is composed of various cells, and the
      enteric nervous system, which controls the epithelial functions, has different
      neurotransmitters and/or modulators. The aim of this study was to show whether
      the responses of intestinal epithelial cells to different neurotransmitters are
      elicited throughout the entire epithelium or are restricted to a certain cell.
      METHODS: The spatiotemporal dynamics of cytosolic calcium ion ([Ca2+]c) were
      measured by digital imaging analysis in isolated crypts of mouse ileum loaded
      with [1-[2-(5'-carboxyoxazol-2'-yl)-6-amino-benzofuran-5- oxy]-2-(2'-amino-5'
      methylphenoxy)-ethane-N,N,N',N'-tetraacetic acid] pentakis (acetoxylmethyl)
      ester. Thereafter, the crypt cells were identified morphologically. RESULTS:
      Carbamylcholine elicited [Ca2+]c dynamics in Paneth cells, showing a biphasic
      increase, but neither cholecystokinin octapeptide nor nicotine had any effect on
      the [Ca2+]c of the crypt cells including the Paneth cells. Adrenaline and
      noradrenaline, but not isoproterenol, induced a transient elevation of [Ca2+]c of
      some enterochromaffin cells. Increases in the [Ca2+]c of most crypt cells were
      elicited by thapsigargin. Propagation of a [Ca2+]c wave in the crypts was not
      evident. CONCLUSIONS: Increases in [Ca2+]c can be induced by carbamylcholine in
      Paneth cells and catecholamines in some enterochromaffin cells. The digital
      imaging analysis showed the heterogeneity of the responses of intestinal crypt
      cells to different transmitters.

PMID- 7729626
TI  - Deglutitive aspiration in patients with tracheostomy: effect of tracheostomy on
      the duration of vocal cord closure.
AB  - BACKGROUND/AIMS: Deglutitive aspiration in patients with tracheostomy has been
      attributed to impaired laryngeal movement, loss of protective laryngeal reflexes,
      and uncoordinated laryngeal closure. The aim of this study was to determine the
      effect of tracheostomy on the duration of deglutitive vocal cord closure.
      METHODS: Using concurrent videoendoscopy, respirography, and submental
      electromyography, deglutitive vocal cord closure and its temporal relationship
      with deglutitive apnea was compared between patients with tracheostomy and normal
      volunteers. RESULTS: Between-group comparison showed that the duration of vocal
      cord adduction/abduction in patients with tracheostomy was significantly shorter
      than that of normal volunteers (P < 0.05). Contrary to normal volunteers, in
      patients with tracheostomy, 5-mL water swallows significantly increased the
      duration of vocal cord adduction/abduction compared with that of dry swallows (P
      < 0.05). In addition, in patients with tracheostomy, deglutitive apnea and
      submental electromyography were not coordinated with vocal cord kinetics.
      CONCLUSIONS: Although the vocal cords close completely during swallowing in
      patients with tracheostomy, their duration of closure is significantly shorter
      compared with normal volunteers. Coordination of deglutitive vocal cord kinetics,
      apnea, and submental electromyography is altered in patients with tracheostomy.
      Contrary to normal controls, duration of deglutitive vocal cord closure in
      patients with tracheostomy is modified by the presence of liquid bolus.

PMID- 7729627
TI  - Low incidence of significant dysplasia in a successful endoscopic surveillance
      program of patients with ulcerative colitis.
AB  - BACKGROUND/AIMS: Colorectal cancer associated with ulcerative colitis may be
      preceded by dysplastic changes potentially detectable by repeated endoscopic
      examinations. The aim of this study was to evaluate the incidence, course, and
      risk factors for dysplasia in a prospective endoscopic study. METHODS: One
      hundred fifty-four patients with ulcerative colitis for 7 or more years' duration
      were followed from 1976 to 1994 in an endoscopic surveillance program. RESULTS:
      Five patients had 10 adenomatous polyps managed by polypectomy. Indefinite
      dysplasia was found in 16 patients, and none showed progressive dysplasia on
      follow-up. Low-grade dysplasia was detected in 10 patients; 2 had and 2
      progressed to high-grade dysplasia. High-grade dysplasia was found in 7 patients;
      4 were concurrent with or just preceded cancer. All 4 cases of cancer were first
      detected by surveillance, and 3 were successfully treated. Significant risk
      factors for dysplasia (all grades) and cancer included the extent of disease (P <
      0.01), older age at onset of colitis (P = 0.01), and the duration of disease (P <
      0.05). The adjusted risk for cancer was significantly increased (P = 0.04).
      CONCLUSIONS: Indefinite dysplasia did not predict developing cancer. Low- or high
      grade dysplasia was not frequent (8.5%) but was associated with progression to
      cancer. These can be detected and successfully treated by systematic endoscopic
      surveillance of patients with chronic (> or = 7 years), extensive (more than the
      rectosigmoid colon) ulcerative colitis.

PMID- 7729628
TI  - Neurogenic control of myoelectric complexes in the mouse isolated colon.
AB  - BACKGROUND/AIMS: Little is known about the mechanisms controlling colonic
      migrating electrical activity. This study investigates the neural processes
      involved in the generation of migrating myoelectric complexes in the isolated
      mouse colon. METHODS: Intracellular electrophysiological recordings were obtained
      from the circular muscle layer of the mouse colon in vitro in the presence of 2
      mumol/L nifedipine. RESULTS: Complexes occurred approximately every 3 minutes and
      consisted of 1 mumol/L hyoscine-sensitive rapid oscillations (approximately 2 Hz)
      superimposed on a slow depolarization (approximately 17 mV); the latter was often
      preceded by a precomplex hyperpolarization (approximately 7 mV) that was reduced
      by 250 nmol/L apamin. Five hundred micromolars of hexamethonium or 2 mumol/L of
      tetrodotoxin abolished the complexes and depolarized the muscle by 8.7 +/- 1.3 mV
      (n = 9) or 12.1 +/- 1.4 mV (n = 5), respectively. Carbachol (50 nmol/L to 5
      mumol/L) produced dose-dependent depolarizations but without rapid oscillations.
      The nitric oxide synthase inhibitor NG-nitro-L-arginine (100 mumol/L) depolarized
      the tissue by 17.2 +/- 1.6 mV (n = 8) but had no effect on the rapid
      oscillations. In the presence of 2 mumol/L tetrodotoxin, 5 mumol/L sodium
      nitroprusside produced a sustained hyperpolarization (15.5 +/- 2.0 mV; n = 5) but
      did not restore complexes. CONCLUSIONS: In the isolated mouse colon, the membrane
      potential between complexes is maintained by the release of inhibitory
      neurotransmitters (including nitric oxide), and the formation of complexes
      involves disinhibition and the simultaneous activation of cholinergic motor
      nerves.

PMID- 7729629
TI  - Intestinal motility and jejunal feeding in children with chronic intestinal
      pseudo-obstruction.
AB  - BACKGROUND/AIMS: Total parenteral nutrition is responsible for most of the
      morbidity and mortality of childhood chronic intestinal pseudo-obstruction (CIP).
      The aim of this study was to determine if there are manometric patterns
      associated with the success of jejunal feedings in children with CIP. METHODS:
      Eighteen children with CIP (age range, 1-9 years; mean, 4 years; 11 boys and 7
      girls) were studied. All patients required parenteral nutrition or failed to
      thrive while receiving gastrostomy feedings. All underwent an antroduodenal
      manometry before surgical placement of a jejunostomy. Continuous drip jejunal
      feeding with an elemental formula was subsequently initiated. Follow-up after
      jejunal feeding was 1.6 years (range, 6 months to 4 years). Jejunal manometry was
      performed 2 months to 1 year after jejunostomy. RESULTS: Jejunal feeding
      eliminated the need for parenteral nutrition in all 9 patients with migrating
      motor complex (MMC) and in 3 of 9 patients without MMC (P < 0.01). The MMC was
      present or absent in both antroduodenal and jejunal manometry in 14 of 18
      children (77.7%). In 10 of 18 children (55%), duodenal and jejunal manometry
      showed similar qualitative abnormalities. CONCLUSIONS: In selected children with
      CIP who fail gastrostomy feeding, jejunal tube feeding is an alternative to
      parenteral nutrition. The presence of MMCs is associated with a successful
      adaptation to jejunal feeding.

PMID- 7729630
TI  - The importance of local acid production in the distribution of Helicobacter felis
      in the mouse stomach.
AB  - BACKGROUND/AIMS: Helicobacter felis colonizes the gastric mucosa of rodents.
      Preliminary studies showed differences in the distribution of the organism in
      different parts of the stomach that seemed related to the secretory capacity of
      the mucosa. The aim of this study was to determine the localization of H. felis
      in the mouse stomach and to investigate the influence of acid-suppressive agents.
      METHODS: Specific-pathogen-free BALB/c mice were infected with H. felis.
      Colonization was assessed in longitudinal sections of gastric tissue from animals
      untreated or treated with omeprazole or ranitidine. RESULTS: In untreated H.
      felis-infected animals, the preferred ecological niche was the antrum and cardia
      equivalent. The density of colonization correlated with the number of parietal
      cells per gland. Partial acid suppression with ranitidine produced a slight
      increase in the colonization of the body but was restricted to the upper portions
      of the gastric gland. Omeprazole treatment produced a greater colonization of the
      body with bacteria traversing the entire gland. Some reduction in antral
      colonization occurred. CONCLUSIONS: These results are consistent with the
      hypothesis that local acid output is a crucial determinant in the distribution of
      Helicobacter species in the stomach. Differences in local acid output may explain
      the different patterns of Helicobacter pylori-induced gastric pathology.

PMID- 7729631
TI  - Immunocytochemical evidence of Listeria, Escherichia coli, and Streptococcus
      antigens in Crohn's disease.
AB  - BACKGROUND/AIMS: Infectious agents have long been suspected of playing a role in
      the initiation of Crohn's disease. The objective of this study was to search for
      likely microbial agents in diseased tissues using immunocytochemical techniques.
      METHODS: Intestines and mesenteric lymph node specimens of 21 patients from two
      French families with a high frequency of Crohn's disease and from Connecticut
      were studied. The microbial agents searched for included Bacteroides vulgatus,
      Borrelia burgdorferi, Escherichia coli, Listeria monocytogenes, Streptococcus
      spp., bovine viral diarrhea virus, influenza A virus, measles virus,
      parainfluenza virus, and respiratory syncytial virus. RESULTS: Seventy-five
      percent of the patients with Crohn's disease (12 of 16) were positively labeled
      with the antibody to Listeria. Macrophages and giant cells immunolabeled for this
      antigen were distributed underneath ulcers, along fissures, around abscesses,
      within the lamina propria, in granulomas, and in the germinal centers of
      mesenteric lymph nodes. In addition, 57% (12 of 21) of the cases contained the E.
      coli antigen, and 44% (7 of 16) contained the streptococcal antigen. The
      immunolabeling for the latter two agents also occurred within macrophages and
      giant cells, distributed in a pattern similar to that of Listeria antigen.
      CONCLUSIONS: The results suggest that Listeria spp., E. coli, and streptococci,
      but not measles virus, play a role in the pathogenesis of Crohn's disease.

PMID- 7729632
TI  - Screening reduces colorectal cancer rate in families with hereditary nonpolyposis
      colorectal cancer.
AB  - BACKGROUND/AIMS: The inherited susceptibility to hereditary nonpolyposis
      colorectal cancer (HNPCC) provides an opportunity for secondary prevention of
      colorectal cancer (CRC) in family members who are at 50% lifetime risk. The aim
      of this study was to evaluate the effectiveness of long-term screening during a
      10-year period. METHODS: The CRC and death rates were compared between two groups
      of asymptomatic at-risk members of 22 families with HNPCC: 133 subjects screened
      at 3-year intervals by colonoscopy or barium enema and sigmoidoscopy and 118
      control subjects without screening. The screening was complete in 118 subjects
      (89%), whereas 18 control subjects (15%) had screening examinations outside of
      the study. RESULTS: CRC occurred in 6 study subjects (4.5%) and in 14 controls
      (11.9%; P = 0.03), a difference of 7.4% in favor of the study group, which
      corresponds to a reduction by 62% that is presumably because of polypectomies.
      The tumor stage was more favorable in the screening group with no deaths caused
      by CRC compared with 5 of 14 cases in controls. Overall, there were 6 and 12
      deaths within the 10-year period in the study and control groups, respectively (P
      = 0.08). CONCLUSIONS: The 3-year interval screening more than halves the CRC rate
      in at-risk members of families with HNPCC and seems to prevent CRC deaths.

PMID- 7729633
TI  - Double-blind trial of omeprazole and amoxicillin to cure Helicobacter pylori
      infection in patients with duodenal ulcers.
AB  - BACKGROUND/AIMS: Anti-Helicobacter pylori treatment with combinations of
      omeprazole and amoxicillin is a promising treatment option. The aim of this study
      was to investigate whether a daily omeprazole dose of 120 mg combined with
      amoxicillin would cure H. pylori infection at a rate comparable with that
      achieved with "triple therapy." METHODS: In a double-blind, randomized,
      controlled, and multicenter trial in Germany, 270 patients with an H. pylori
      associated duodenal ulcer were treated with 40 mg omeprazole three times a day
      and 750 mg amoxicillin three times a day for the first 14 days (n = 139) followed
      by 20 mg omeprazole once daily until day 42 or with omeprazole plus 750 mg
      amoxicillin placebo three times a day for the same time period (n = 131).
      RESULTS: Cure rates of H. pylori infection were 91% in the omeprazole plus
      amoxicillin group, 0% in the omeprazole plus placebo group, and 89% and 0%,
      respectively, performing an intention-to-treat analysis. Cure of H. pylori
      infection in patients pretreated with omeprazole was only 58% compared with 95%
      in patients who were not. The cumulative 12-month relapse rates were 11.3% and
      44% in the treatment groups and 1.6% in H. pylori-negative and 49% in H. pylori
      positive patients. CONCLUSIONS: The combination of 120 mg omeprazole daily and
      2.25 g amoxicillin daily with its H. pylori cure rate of around 90% is one of the
      best tolerated and most effective treatment regimens.

PMID- 7729634
TI  - Deglutitive tongue force modulation by volition, volume, and viscosity in humans.
AB  - BACKGROUND/AIMS: Deglutitive tongue biomechanics are complex, involving bolus
      containment, loading, and propulsion. This study aimed to quantify the modulation
      of deglutitive pulsive and clearing tongue forces in varied swallowing
      conditions. METHODS: Oropharyngeal pressure and force were recorded using sensing
      bulbs and strain-gauge manometry in 8 volunteers during swallows of varied volume
      and viscosity. Volitional modulation was explored with forceful and attenuated
      swallows. RESULTS: Temporal analysis confirmed that bulb recordings corresponded
      to tongue pulsive force, and the strain-gauge recordings measured tongue clearing
      pressure. Volition was the most potent modifier of both tongue pulsive force and
      clearing pressure with values showing a fourfold increase from attenuated to
      forceful swallows. Bolus viscosity also induced an increase of tongue pulsive
      force and clearing pressure by the oral tongue. Volitional control as well as
      adaptation to viscosity was greatest on the anterior and middle part of the oral
      tongue. There was no force adaptation with increased bolus volume. CONCLUSIONS:
      Tongue pulsive force and clearing pressure during swallow showed substantial
      modulation for bolus viscosity that can be reproduced by volitional control. The
      anterior two thirds of the tongue showed both greater forces and greater
      modulation than did the tongue base.

PMID- 7729635
TI  - Delivery and fate of oral mesalamine microgranules within the human small
      intestine.
AB  - BACKGROUND/AIMS: Oral use of mesalamine in inflammatory bowel disease requires
      slow-release preparations to prevent premature absorption and inactivation.
      Resulting luminal concentrations within the human small intestine are unknown.
      The aim of this study was to determine human intestinal delivery patterns of
      mesalamine from a microgranule preparation (Pentasa; Ferring Arzeimittel, Kiel,
      Germany) effective in Crohn's disease with small bowel involvement. METHODS: A
      multilumen tube for duodenal, jejunal, and ileal aspiration and marker perfusion
      was placed in 6 normal subjects. Levels of luminal, plasma, and urinary
      mesalamine and its main metabolite, acetyl mesalamine, were measured for 7 hours
      after ingestion of mesalamine (500 mg) with a labeled meal. RESULTS: Gastric
      emptying of mesalamine paralleled the meal, and its release occurred throughout
      the small intestine (cumulative, 20% of dose). For 4 hours, mean luminal
      mesalamine and acetyl mesalamine concentrations were 52 and 38 micrograms/mL
      (duodenum), 59 and 82 micrograms/mL (jejunum), and 64 and 104 micrograms/mL
      (ileum). Cumulative colonic delivery was 82% (7% dissolved, 75% in
      microgranules), and urinary excretion was 3.5%. CONCLUSIONS: Although the major
      part of continuous-release mesalamine is delivered to the colon, large
      proportions are liberated and available at high concentrations within the small
      intestinal lumen, thus explaining its therapeutic efficacy in small intestinal
      Crohn's disease.

PMID- 7729636
TI  - Immunoregulatory role of interleukin 10 in patients with inflammatory bowel
      disease.
AB  - BACKGROUND/AIMS: Active inflammatory bowel disease (IBD) is associated with
      increased proinflammatory cytokines. Deficiency of interleukin (IL) 10, a
      contrainflammatory cytokine, leads to the development of colitis in IL-10
      knockout mice. We characterized IL-10 regulation of proinflammatory cytokine
      (tumor necrosis factor [TNF] alpha and IL-1 beta) expression in IBD in vitro and
      in vivo. METHODS: IL-10 regulation of IL-1 beta, TNF-alpha, and IL-1 receptor
      antagonist expression by peripheral monocytes or isolated lamina propria
      mononuclear cells (LPMNC), respectively, was studied by enzyme-linked
      immunosorbent assay (cytokine secretion) and by semiquantitative reverse
      transcription polymerase chain reaction. RESULTS: IL-10 down-regulates IL-1 beta
      and TNF-alpha secretion as well as messenger RNA levels in IBD peripheral
      monocytes and LPMNC in a dose-dependent manner. In parallel, IL-1 receptor
      antagonist secretion is induced, and IL-10 can restore diminished in vitro IL-1
      receptor antagonist/IL-1 beta ratios in IBD to normal levels. Equal
      concentrations of IL-10 are detectable in both normal and IBD intestinal lamina
      propria biopsy homogenates. After topical IL-10 enema treatment of three steroid
      therapy-refractory patients with ulcerative colitis, in vitro release of
      proinflammatory cytokines from IBD peripheral monocytes as well as LPMNC is
      dramatically down-regulated. CONCLUSIONS: IL-10 down-regulates the enhanced
      secretion as well as messenger RNA levels of proinflammatory cytokines by IBD
      mononuclear phagocytes in vitro. In vivo topical application of IL-10 induces
      down-regulation of proinflammatory cytokine secretion both systemically and
      locally.

PMID- 7729637
TI  - Circulating pancreastatin is a marker for the enterochromaffin-like cells of the
      rat stomach.
AB  - BACKGROUND/AIMS: Peptides of the chromogranin family occur in peptide hormone
      producing cells throughout the body. One source of such peptides is the
      enterochromaffin-like (ECL) cells, which constitute the predominant population of
      endocrine cells in the fundus (the acid-producing part) of the rat stomach. The
      purpose of this study was to examine whether ECL cells, which are controlled by
      gastrin, represent a major source of circulating pancreastatin, a fragment of
      chromogranin A. METHODS: Rats underwent surgical procedures and treatments in
      which the ECL cells could be manipulated. The procedures included antrectomy,
      fundectomy, and gastrectomy (and adrenalectomy), and the treatments included
      fasting or feeding, gastrin-17 infusion, and administration of omeprazole or
      ranitidine. The concentrations of pancreastatin-like immunoreactivity (LI) and
      gastrin in the serum were determined by radioimmunoassay. RESULTS: The serum
      pancreastatin-LI concentration was lowered by about 80% by fundectomy and
      gastrectomy; both of these procedures eliminated the ECL cell population.
      Adrenalectomy had no effect on the serum pancreastatin-LI concentration. Gastrin
      infusion, which activates the ECL cells, promptly increased serum pancreastatin
      LI concentration. Refeeding after fasting and administration of omeprazole or
      ranitidine increased the serum pancreastatin-LI concentrations; these responses
      were prevented by antrectomy. CONCLUSIONS: The concentration of circulating
      pancreastatin-LI reflects the activity of the ECL cells and the size of the ECL
      cell population in the rat stomach.

PMID- 7729638
TI  - Tumor necrosis factor receptors in patients with chronic hepatitis B virus
      infection.
AB  - BACKGROUND/AIMS: Patients with chronic hepatitis B infection have elevated plasma
      tumor necrosis factor (TNF) alpha levels. Two TNF-alpha receptors have been
      identified, each responsible for distinct TNF-alpha activities. The aim of this
      study was to evaluate the biological function of the elevated TNF-alpha in
      chronic hepatitis B virus infection by examining the two TNF signaling pathways
      in the evolution of hepatitis B-related liver injury. METHODS: The hepatic
      expression of the two TNF receptors and the corresponding serum levels of the
      soluble forms of both TNF receptors were determined and correlated with hepatic
      inflammation and virus replication in 98 chronic hepatitis B surface antigen
      carriers. Forty hepatitis B e antigen-positive patients were also studied
      prospectively, while on interferon alfa treatment, to examine the TNF receptor
      response during viral clearance. RESULTS: In chronic hepatitis B virus infection,
      the hepatic expression and serum levels of TNF receptors, in particular 75
      kilodalton TNF receptor subtype (TNF-R p75), are significantly enhanced in
      association with hepatic inflammation and hepatocytolysis but not with hepatitis
      B virus replication. During interferon alfa treatment, a significant increase of
      soluble TNF-R p75 always precedes the hepatitis B e antigen antibody against
      hepatitis B e antigen seroconversion in responders to treatment. CONCLUSIONS: In
      chronic active hepatitis B infection, there is an up-regulation of the TNF
      receptor system, preferentially the TNF-R p75 signaling pathway, which suggests
      that the TNF-alpha/TNF receptor system has an important role in the pathogenesis
      of liver damage and viral clearance.

PMID- 7729639
TI  - Localization of uridine 5'-diphosphate-glucuronosyltransferase in human liver
      injury.
AB  - BACKGROUND/AIMS: Pharmacokinetic studies in patients with cirrhosis have shown a
      decreased clearance of drugs metabolized by cytochrome P450, whereas drugs
      metabolized by glucuronidation frequently have a normal elimination. The
      mechanism for the apparent preservation of glucuronidation has not been
      elucidated. The aim of this study was to examine the expression of uridine 5'
      diphosphate-glucuronosyltransferase (UGT) in human liver injuries. METHODS: UGT
      was measured by immunohistochemistry using a UGT polyclonal antibody, which was
      then compared with a representative isoform of cytochrome P450. Normal liver
      biopsy specimens (n = 8) and a spectrum of liver injury biopsy specimens (n = 47)
      were examined. RESULTS: Compared with normal liver, increased staining for UGT in
      remaining hepatocytes was seen in liver damaged by chronic alcohol abuse, but the
      most intense immunoreactivity was observed in remaining and regenerative
      hepatocytes in specimens with cirrhosis. Primary biliary cirrhosis showed
      diffusely increased immunoreactivity. Other nonmalignant groups showed an
      increased staining relative to chronicity of liver disease. In contrast, in all
      liver injuries, cytochrome P450 staining was reduced as compared with controls.
      CONCLUSIONS: Chronic liver damage results in increased UGT in remaining viable
      hepatocytes. Mechanisms may operate in liver injury to preserve expression of UGT
      in functional hepatocytes, and this may explain the preservation of
      glucuronidation in cirrhosis.

PMID- 7729640
TI  - A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine
      and ursodeoxycholic acid.
AB  - BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) and colchicine have beneficial
      effects in primary biliary cirrhosis (PBC). The efficacy of colchicine and UDCA
      in PBC was compared in a 2-year placebo-controlled study (n = 90). METHODS:
      Clinical events, laboratory test results, and liver histology were recorded at
      the beginning and end of the trial. RESULTS: There were significantly fewer
      dropouts for hepatic reasons with UDCA than with placebo. Pruritus was reduced by
      both active drugs. Colchicine improved liver function test results only modestly,
      whereas UDCA significantly decreased the serum activities of aminotransferases,
      alkaline phosphatase, and gamma-glutamyltransferase compared with colchicine and
      placebo. Serum total bilirubin levels were decreased only by UDCA. Both
      colchicine and UDCA reduced serum cholesterol levels, and UDCA also reduced high
      density lipoprotein cholesterol levels. Furthermore, UDCA reduced the serum
      levels of immunoglobulin (Ig) M and IgG, and colchicine reduced IgG levels
      compared with placebo. The elevated serum level of aminoterminal propeptide of
      type III procollagen remained unchanged by colchicine or UDCA, whereas the serum
      level of carboxyterminal propeptide of type I procollagen was significantly
      decreased by UDCA. UDCA significantly decreased ductular proliferation compared
      with colchicine or placebo. CONCLUSIONS: These data suggest that UDCA frequently
      is superior to colchicine and especially to placebo in the treatment of PBC.

PMID- 7729641
TI  - Increased opioid binding to peripheral white blood cells in a rat model of acute
      cholestasis.
AB  - BACKGROUND/AIMS: Endogenous opioids accumulate in plasma in cholestasis.
      Furthermore, immune cells have opioid receptors, and endogenous opioids have
      immunomodulatory effects. This study examined the expression of opioid receptors
      on peripheral white blood cells in rats with acute cholestasis after bile duct
      resection (BDR). METHODS: Five days after surgery, white blood cells were
      isolated from peripheral blood. To determine total opioid binding, cells from
      either BDR or sham-resected rats were incubated with a fluorescently labeled
      opioid receptor antagonist. Specific opioid binding was determined by
      preincubating the cells with a 100-fold molar excess of unlabeled naltrexone or
      with one of two opioid receptor agonists: (D-Ala2, D-Leu5)-enkephalin (delta
      receptor) or (D-Ala2, MePhe4, Gly-ol5)enkephalin (mu receptor). The proportion of
      neutrophils, lymphocytes, and monocytes with specific delta or mu opioid
      receptors was determined by flow cytometric analysis. RESULTS: Opioid receptors
      on neutrophils were unaffected by BDR, whereas the lymphocyte population of BDR
      rats had an increased binding to delta receptors (2.6% +/- 1.1% for sham vs. 7.3%
      +/- 1.4% for BDR; P < 0.02) and monocytes from BDR rats had an increased binding
      to mu receptors (7.7% +/- 0.9% for sham vs. 17.9% +/- 2.3% for BDR; P < 0.0001).
      CONCLUSIONS: The selective increase of delta-receptor binding on lymphocytes and
      mu-receptor binding on monocytes suggests that, in acute cholestasis, opioid
      mediated effects on white blood cell function may be altered.

PMID- 7729642
TI  - Cirrhosis with ascites: increased atrial natriuretic peptide messenger RNA
      expression in rat ventricle.
AB  - BACKGROUND/AIMS: Atrial natriuretic peptides (ANPs) are increased in the
      circulation of cirrhotics with ascites; however, it is unknown whether this
      increase is caused by increased synthesis or a decrease in the metabolic
      processing of these peptides. ANP gene expression in the liver, atria,
      ventricles, and gastrointestinal tract of cirrhotic vs. control rats was studied
      as was their metabolism. METHODS: Sprague-Dawley rats developed cirrhosis with
      ascites approximately 20 weeks after weekly intragastric instillation of carbon
      tetrachloride. Their circulating, ascitic, and urinary levels of ANPs were
      measured by radioimmunoassays. ANP gene expression was measured by a ribonuclease
      protection assay. RESULTS: ANP gene expression was increased 2.8- to 4.1-fold in
      the ventricles of cirrhotic rats compared with age-matched healthy rats. ANP gene
      expression was present but not increased in the liver, atria, and
      gastrointestinal tract of cirrhotic rats. No increase of metabolic processing of
      these peptides was found in the circulation. Cardiac ultrasonography and
      catheterization revealed no ventricular dilation or increased ventricular
      pressure. CONCLUSIONS: Elevation of circulating ANPs with cirrhosis was
      associated with increased ventricular steady-state ANP messenger RNA
      concentrations. The increased ANP gene expression in cirrhosis seems to involve a
      novel mechanism not related to stretch because neither increased ventricular
      pressure nor dilation was present.

PMID- 7729643
TI  - Oxygen supplementation restores theophylline clearance to normal in cirrhotic
      rats.
AB  - BACKGROUND/AIMS: Capillarization associated with hepatic fibrosis may present a
      functional barrier to oxygen diffusion into the hepatocyte, and restriction on
      cellular oxygen supply may represent the rate-limiting constraint on hepatic
      oxidative drug metabolism. The aim of this study was to test this hypothesis by
      examining the effect of oxygen supplementation on plasma theophylline clearance
      in 10 control and 10 cirrhotic rats. METHODS: Theophylline (3 mg/kg) was
      administered intravenously on two separate occasions, 24 hours apart, during
      which time the rats breathed either room air or oxygen (95%) from 1 hour before
      dosing until the end of plasma sampling with a randomized order of gas exposure.
      RESULTS: Theophylline clearance was significantly reduced by a mean of 37% (n =
      10; P = 0.003) in cirrhotic rats compared with controls. Oxygen supplementation
      significantly improved plasma theophylline clearance in cirrhotic rats by a mean
      of 40% (n = 10; P = 0.007), whereas clearance remained unchanged in healthy rats.
      Clearance in oxygen-supplemented cirrhotic rats was not significantly different
      from that in controls (P > 0.05). CONCLUSIONS: These novel findings indicate an
      important role for hepatic oxygenation in improving drug disposition in
      cirrhosis, which may have potentially important clinical implications for the
      management of this disease.

PMID- 7729644
TI  - Evidence for the detrimental role of proteolysis during liver preservation in
      humans.
AB  - BACKGROUND/AIMS: Proteolysis may persist in the liver allograft during cold
      storage. The aim of this study was to determine the significance of proteolysis
      within liver allografts stored at 4 degrees C in University of Wisconsin
      preservation fluid. METHODS: Thirty recipients of 32 liver allografts were
      studied prospectively. Amino acid content of the preservation fluid was analyzed
      at the end of cold storage and was correlated to graft and patient outcome after
      transplantation. RESULTS: Analysis of the preservation fluid showed the presence
      of free amino acids, the profile of which was different from that of stored liver
      parenchyma. Concentrations of amino acids (alanine, cysteine, leucine,
      isoleucine, methionine, lysine, ornithine, and threonine) and transaminases
      (alanine aminotransferase and aspartate aminotransferase) in the preservation
      fluid correlated with the duration of cold ischemia. Indexes of graft dysfunction
      (serum alanine aminotransferase and aspartate aminotransferase peaks and
      prothrombin rate) correlated with concentrations of cysteine, alanine,
      isoleucine, leucine, methionine, lysine, ornithine, and threonine, whereas enzyme
      concentrations in the fluid were not predictive of graft dysfunction.
      CONCLUSIONS: These data suggest that liver proteolysis occurs during cold storage
      and may have a detrimental effect on the outcome after transplantation. The
      measurement of the amino acids in the preservation fluid at the end of the cold
      storage period could help to identify the most severely damaged organs.

PMID- 7729645
TI  - Pancreatic polypeptide microinjection into the dorsal motor nucleus inhibits
      pancreatic secretion in rats.
AB  - BACKGROUND/AIMS: Pancreatic polypeptide (PP), a hormone released from the
      pancreas, inhibits pancreatic secretion in vivo but not in vitro, suggesting that
      the inhibitory action of PP on pancreatic secretion is indirect. Circulating PP
      in physiological concentrations binds to specific receptors in the dorsal vagal
      complex in the brainstem. Therefore, the hypothesis of this study was that PP
      acts centrally and inhibits pancreatic secretion by modulating vagal tone.
      METHODS: The effects of microinjection of PP into the dorsal motor nucleus on 2
      deoxy-D-glucose-stimulated and cholecystokinin octapeptide (CCK-8)-stimulated
      pancreatic secretion were examined in urethane-anesthetized rats. RESULTS:
      Microinjection of PP to the dorsal motor nucleus but not brainstem sites outside
      it inhibited 2-deoxy-D-glucose-stimulated pancreatic flow and protein output. CCK
      8-stimulated pancreatic protein output was inhibited by PP in the dorsal motor
      nucleus in dose-dependent and site-specific manners. The inhibitory effect of PP
      on CCK-8-stimulated protein output was eliminated by vagotomy. CONCLUSIONS: The
      results suggest that PP acts in the dorsal motor nucleus to modulate vagal tone
      on the pancreas, thereby inhibiting pancreatic secretion. This study shows for
      the first time that the dorsal motor nucleus is involved in central feedback
      inhibition of the exocrine pancreas.

PMID- 7729646
TI  - Primary dual defect of cholesterol and bile acid metabolism in liver of patients
      with intrahepatic calculi.
AB  - BACKGROUND/AIMS: Intrahepatic calculi, which are characterized by cholesterol
      rich pigment stones, are highly prevalent in East Asia. Their pathogenesis
      remains unknown. To elucidate the etiological factors underlying the formation of
      cholesterol-supersaturated bile, which leads to the formation of cholesterol-rich
      pigment stones cholesterol and bile acid de novo syntheses in the liver were
      studied. METHODS: Liver specimens were assayed for the catalytic activities and
      steady-state messenger RNA levels of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG
      CoA) reductase and cholesterol 7 alpha-hydroxylase. RESULTS: The activity of HMG
      CoA reductase, consistent with the messenger RNA level, was significantly higher
      in 13 patients with intrahepatic grown pigment stones (11.2 +/- 1.3 pmol.min-1.mg
      protein-1 [mean +/- SEM; P < 0.0001] for affected hepatic lobes and 13.4 +/- 1.7
      [P < 0.0001] for unaffected ones [P < 0.0001]) than in 19 control subjects (6.4
      +/- 0.4) and in 29 patients with gallbladder cholesterol stones (2.1 +/- 0.1). On
      the other hand, the activity of 7 alpha-hydroxylase, consistent with the
      messenger RNA level, was significantly lower in patients with intrahepatic brown
      pigment stones (2.8 +/- 0.5 pmol.min-1.mg protein-1 [P < 0.0001] for affected
      lobes and 2.6 +/- 0.5 [P < 0.0001] for unaffected ones) than in control subjects
      (6.0 +/- 0.6) and in patients with cholesterol stones (5.1 +/- 0.5). CONCLUSIONS:
      In intrahepatic calculi, the formation of supersaturated bile and cholesterol
      rich pigment stones may be attributed to the primary dual defect of up-regulated
      cholesterogenesis and down-regulated bile acid synthesis in the liver.

PMID- 7729647
TI  - Octreotide promotes gallbladder absorption in prairie dogs: a potential cause of
      gallstones.
AB  - BACKGROUND/AIMS: Gallstone formation during octreotide administration has been
      causally linked to increased biliary concentrations of calcium, protein, and
      total lipids, all purported prolithogenic factors. These changes may be caused by
      octreotide-induced gallbladder stasis or a direct effect of octreotide on
      gallbladder absorption. We tested the hypothesis that octreotide stimulates
      gallbladder ion and water transport. METHODS: Prairie dog gallbladders were
      mounted in Ussing chambers and bathed in oxygenated Ringer's solution.
      Electrophysiological parameters were recorded, and unidirectional Na+, Cl-, and
      H2O fluxes were measured before and after serosal exposure to 50 nmol/L
      octreotide. RESULTS: Octreotide exposure caused a significant decrease in
      transepithelial short-circuit current and potential difference and an increase in
      tissue resistance compared with baseline. These alterations in
      electrophysiological parameters coincided with changes in ion transport.
      Octreotide stimulated net Na+ and H2O absorption and converted the gallbladder
      from a state of Cl- secretion to one of Cl- absorption by increasing mucosal to
      serosal fluxes. Octreotide effects on ion transport were blocked by 4,4'
      diisothiocynostilbene-2,2'-disulfonic acid and amiloride and reversed by
      theophylline. CONCLUSIONS: Octreotide may promote gallstone formation by inducing
      gallbladder stasis and by directly increasing gallbladder absorption, which may
      act synergistically to increase the concentration of prolithogenic factors in
      bile and to facilitate nucleation and stone growth.

PMID- 7729648
TI  - Colonic obstruction secondary to sarcoidosis: nonsurgical diagnosis and
      management.
AB  - A 57-year-old black man presented with a 2-week history of abdominal pain, weight
      loss, anorexia, and constipation. His history was significant for remote
      Hodgkin's disease and systemic sarcoidosis. Physical examination showed abdominal
      distention and hyperactive bowel sounds, periorbital swelling, and mandibular
      lymphadenopathy. A barium enema examination showed two high-grade obstructive
      lesions in the rectum and splenic flexure. Colonoscopy confirmed the presence of
      the two areas of colonic obstruction. The mucosa showed diffuse fine ulcerations
      in the areas of obstruction as well as in the intervening region. Endoscopic
      biopsy specimens showed numerous mucosal noncaseating granulomas but no acid-fast
      bacilli or foreign bodies. The patient was treated with oral prednisone and
      improved symptomatically within 3 days. The ocular lesions and lymphadenopathy
      also responded promptly. Findings of follow-up barium enema and colonoscopy
      performed after 1 month of steroid treatment were essentially normal. Mucosal
      biopsy specimens showed only mild nonspecific chronic inflammation of the lamina
      propria and no granulomas. Colonic involvement is rarely reported with systemic
      sarcoidosis. We believe that this is the first report of colonic obstruction due
      to sarcoid diagnosed endoscopically and managed nonsurgically.

PMID- 7729649
TI  - Pneumatosis cystoides intestinalis and high breath H2 excretion: insights into
      the role of H2 in this condition.
AB  - Patients with pneumatosis cystoides intestinalis have been reported to excrete
      excessive H2 because of a lack of H2-consuming intestinal bacteria. This study
      describes a patient with bacterial overgrowth and pneumatosis of the small
      intestine whose colonic flora avidly consumed H2 but whose small bowel flora
      produced but did not consume H2. There is no commonly accepted mechanism whereby
      excessive luminal H2 causes intramural gas. An explanation is proposed in which
      an initial, transitory source of intramural gas is distinguished from the
      mechanism that results in the persistence of the gas. Independent of the initial
      source of gas, rapid diffusion of H2 from the lumen into an intramural gas bubble
      would cause N2, O2, and CO2 to diffuse from the blood into the bubble. As a
      result, the bubble would expand and then persist indefinitely as long as H2
      continued to diffuse from the lumen to the intramural gas collection.

PMID- 7729650
TI  - Intestinal permeability: an overview.
AB  - The noninvasive assessment of intestinal permeability in humans has a 20-year
      history. Because the tests are increasingly used in clinical practice and
      research and because there is much controversy, we reviewed the literature and
      outlined the potential and possible shortcomings of these procedures. Data was
      obtained from personal files and from a systemic search through MEDLINE and
      EMBASE. The principle of the differential urinary excretion of orally
      administered test markers is explained with reference to the desired
      physicochemical properties of the markers and how the principle can be exploited
      to allow assessment of various other gastrointestinal functions. The use of
      intestinal permeability tests for diagnostic screen for small bowel disease and
      assessment of responses to treatment, the pathogenesis of disease, normal
      intestinal physiology, and the effect of drugs and toxins on the intestine is
      described and reviewed. The controversy surrounding the anatomic location of the
      permeation pathways that the markers use is highlighted. Noninvasive tests of
      intestinal permeability have fulfilled early promises of usefulness in clinical
      practice and research. There is now a need for integrated research into the basic
      mechanisms of regulatory control of the intestinal barrier function.

PMID- 7729651
TI  - The pruritus of cholestasis: potential pathogenic and therapeutic implications of
      opioids.

PMID- 7729652
TI  - Listeria: the latest putative pathogenetic microorganism in Crohn's disease.

PMID- 7729653
TI  - Aggressive polyps in hereditary nonpolyposis colorectal cancer: targets for
      screening.

PMID- 7729654
TI  - Colchicine and ursodeoxycholic acid for primary biliary cirrhosis: emerging
      results.

PMID- 7729655
TI  - Is proteolysis a critical mechanism of hepatic preservation injury?

PMID- 7729656
TI  - A newly recognized source of Escherichia coli O157:H7 infections.

PMID- 7729657
TI  - Absorptive hyperemia.

PMID- 7729658
TI  - Zollinger-Ellison syndrome: surgery should still play an important role in its
      management.

PMID- 7729659
TI  - Human papillomavirus and esophageal squamous cell carcinoma.

PMID- 7729660
TI  - Human papillomavirus and esophageal squamous cell carcinoma.

PMID- 7729661
TI  - Prognosis in nonalcoholic steatohepatitis.

PMID- 7729662
TI  - Determinants of bone density in inflammatory bowel disease.

PMID- 7729663
TI  - Neurobiology of sleep and human colonic motor patterns.

PMID- 7729664
TI  - Is aberrant abnormal?

PMID- 7729665
TI  - Low-grade dysplasia in ulcerative colitis.

PMID- 7729666
TI  - The subtilisins of the invertebrate mycopathogens Verticillium chlamydosporium
      and Metarhizium anisopliae are serologically and functionally related.
AB  - The major extracellular proteases from the nematophagous fungus Verticillium
      chlamydosporium and the entomophagous fungus Metarhizium anisopliae, VCP1 and
      Pr1, respectively, are closely related both functionally and serologically.
      Antibodies raised against either enzyme cross-reacted with both antigens,
      suggesting that they have common epitopes. The VCP1 and Pr1 antisera labelled
      bovine pancreatic elastase and proteinase K, respectively. Neither antiserum
      reacted with commercial chymotrypsin. An antiserum to a serine protease from the
      closely related V. suchlasporium also cross-reacted with VCP1 and Pr1. In
      contrast, a polyclonal antibody to an isoform of Pr1 exclusive to M. anisopliae
      isolate ME1 failed to recognize Pr1 from M. anisopliae V245 or VCP1. The N
      terminal amino acid sequence of VCP1 revealed similarities with subtilisin-like
      enzymes from other fungi, but the closest match was with Pr1. The pure enzymes,
      VCP1 and Pr1, failed to hydrolyse mono-aminoacyl-naphthylamide substrates but
      demonstrated dipeptidyl peptidase activity against Gly-Pro-beta NA and Leu-Ala
      beta NA, respectively. These results are discussed in the context of specificity
      of invertebrate mycopathogens.

PMID- 7729667
TI  - Cloning and nucleotide sequence of the signal peptidase II (lsp)-gene from
      Staphylococcus carnosus.
AB  - Staphylococcus carnosus TM300 is able to synthesize at least seven lipoproteins
      with molecular masses between 15 and 45 kDa; the proteins are located in the
      membrane fraction. It can be concluded that this strain also posesses the enzymes
      involved in lipoprotein modification and prolipoprotein signal peptidase (signal
      peptidase II) processing. The gene encoding the prolipoprotein signal peptidase,
      lsp, from Staphylococcus carnosus TM300 was cloned in Escherichia coli and
      sequenced. The deduced amino acid sequence of the Lsp showed amino acid
      similarities with the Lsp's of S. aureus, Enterobacter aerogenes, E. coli, and
      Pseudomonas fluorescens. The hydropathy profile reveals four hydrophobic segments
      which are homologous to the putative transmembrane regions of the E. coli signal
      peptidase II. E. coli strains carrying lsp of S. carnosus exhibited an increased
      globomycin resistance.

PMID- 7729668
TI  - Randomly amplified polymorphic DNA fingerprinting identifies subgroups of
      Trichoderma viride and other Trichoderma sp. capable of chestnut blight
      biocontrol.
AB  - Eleven strains of Trichoderma viride, 2 strains of the putative teleomorph
      Hypocrea rufa and 9 of several other Trichoderma sp. were characterized by random
      polymorphic DNA amplification (RAPD) fingerprinting and screened for their
      ability to antagonize growth of European strains of the chestnut blight causing
      fungus Cryphonectria parasitica, using a dual-culture assay. The best strains
      were found in the species T. harzianum, T. parceramosum, a distinguishable
      subgroup of T. viride and a not named Trichoderma sp. The successful application
      of these strains against chestnut blight in vivo is demonstrated.

PMID- 7729669
TI  - Acid adaptation in Streptococcus mutans UA159 alleviates sensitization to
      environmental stress due to RecA deficiency.
AB  - A RecA-deficient stain of Streptococcus mutans, isolated previously, was found to
      be more susceptible than the prototroph organism to acid killing and also showed
      reduced colony-forming ability on sucrose-containing medium. The deficient strain
      was able to grow in chemostat culture at a low pH value of 5 and did not show
      reduced capacity to produce acid in standard pH-drop experiments with excess
      glucose. Moreover, it was able to undergo an adaptive response when grown at a
      low pH to become more resistant to acid killing and also to killing by
      ultraviolet radiation or hydrogen peroxide. In fact, after adaptation, it was
      nearly as resistant as the prototroph strain. These findings were interpreted, in
      part, in terms of an acid-inducible DNA repair system which functions
      independently of RecA.

PMID- 7729670
TI  - Construction of a recombinant wine yeast strain expressing a fungal pectate lyase
      gene.
AB  - A gene fusion between the Saccharomyces cerevisiae actin gene promoter and the
      cDNA of the Fusarium solani f. sp. pisi pelA gene has been constructed. This
      expression cassette has been introduced into the industrial wine yeast strain
      T73. The resulting recombinant strain is able to secrete active PELA enzyme into
      the culture medium. In preliminary microvinification experiments the wine
      produced by this pectinolytic strain is indistinguishable from wine produced
      using the non-transformed strain on the basis of the chemical analyses. Large
      scale fermentations need to be carried out in order to assess the effects on
      filtrability.

PMID- 7729671
TI  - Taxonomy of Corynebacterium diphtheriae and related taxa, with recognition of
      Corynebacterium ulcerans sp. nov. nom. rev.
AB  - Levels of genomic DNA relatedness were determined using a S1 nuclease procedure
      for reference bacteria identified as biotypes of Corynebacterium diphtheriae,
      biovars of Corynebacterium pseudotuberculosis, and 'Corynebacterium ulcerans'.
      These results showed that the three species are separate taxa at the
      genomospecies level whereas biotypes and biovars are closely related genomically
      within each species. Phylogenetic analyses of small-subunit rDNA sequences
      revealed that 'Corynebacterium ulcerans' forms a tight cluster with
      Corynebacterium pseudotuberculosis within the robust branch that groups all
      Corynebacterium sequenced to date. Therefore, we propose that the species
      incertae sedis 'C. ulcerans' should be conclusively recognized as a distinct
      species within the genus Corynebacterium with strain CCUG 2708 = NCTC 7910 as
      type strain. This species is characterized by urease production and fermentation
      of glycogen.

PMID- 7729672
TI  - Purification and characterization of the 3-hydroxybenzoate-6-hydroxylase from
      Klebsiella pneumoniae.
AB  - We isolated 3-hydroxybenzoate-6-hydroxylase (E.C.1.14.13.), an inducible enzyme
      that catalyzed the para-hydroxylation of 3-hydroxybenzoate (3-HBA) to 2,5
      dihydroxybenzoate, from Klebsiella pneumoniae. Although the enzyme was found to
      be mainly induced by its substrate, a coordinated induction of 3-hydroxybenzoate
      hydroxylase and gentisate dioxygenase was also observed in the presence of the
      product of the reaction. The purified enzyme was a monomer with a molecular mass
      of 42,000. It contained FAD as a prosthetic group, utilized NADH or NADPH with
      similar efficiencies and its activity was inhibited by Cu2+, Fe2+ and Hg2+. Other
      properties, such as induction mechanism and kinetic parameters were also studied.
      Moreover, for the first time the amino acid composition of a 3-hydroxybenzoate-6
      hydroxylase was determined.

PMID- 7729673
TI  - Cold-sensitive conditional mutations in Era, an essential Escherichia coli
      GTPase, isolated by localized random polymerase chain reaction mutagenesis.
AB  - Conditional cold-sensitive mutations in Era, an essential Escherichia coli
      GTPase, were isolated. Localized random polymerase chain reaction (PCR)
      mutagenesis employing Taq and T7 DNA polymerases under error prone amplification
      conditions was exploited to generate mutations in the era gene. A plasmid
      exchange technique was used to identify conditional cold-sensitive mutations in
      Era that give rise to defective cell growth below 30 degrees C. Three recessive
      missense mutations in Era, N26S, A156D, and E200K, were isolated. All three
      mutations are located at residues conserved in Era homologues from Streptococcus
      mutans and Coxiella burnetti.

PMID- 7729674
TI  - Genetics of high level penicillin resistance in clinical isolates of
      Streptococcus pneumoniae.
AB  - Mosaic penicillin-binding proteins (PBP) 1A, 2X and 2B genes were cloned from
      four clinical isolates of Streptococcus pneumoniae with levels of susceptibility
      to penicillin ranging from 1.5 to 16 micrograms benzylpenicillin ml-1. In each
      instance it was possible to transform either the penicillin-sensitive laboratory
      strain R6 or a sensitive clinical isolate 110K/70 to the full level of penicillin
      resistance with these three penicillin-binding proteins alone. Until now it has
      not been possible to clearly determine whether alterations to PBP1A, 2X and 2B
      alone were sufficient to attain high level penicillin resistance.

PMID- 7729675
TI  - Nucleotide and deduced amino acid sequence of the gene for a novel protein with a
      possible regulatory function encoded in the beta operon of Staphylococcus aureus.
AB  - Although considerable homology exists between the translation products of the
      rplL, rpoB and rpoC genes of the beta operons of the Gram-negative organism
      Escherichia coli and the Gram-positive Staphylococcus aureus the region between
      the rplL and rpoB genes is quite different in the two bacterial species. In E.
      coli the 324 bp has three centres of dyad symmetry in the first half of the
      sequence and multiple nonsense codons in all three reading frames. By contrast,
      the corresponding region in S. aureus consists of 1000 bp capable of forming a
      similar arrangement of stem-loop structures but with an open reading frame, sited
      177 bp downstream of the end of rplL and 217 bp upstream of the beginning of the
      rpoB gene, with consensus initiation and termination signals, which if translated
      would generate a 22,665 Da protein with 202 amino acids. In view of the inability
      to find any significant homology with other proteins in the data bank and because
      the evidence suggests, as in E. coli, that the rplL-rpoB intergenic sequence is
      involved in regulation it is proposed that the expression product of orf202 may
      be a further element of control in the S. aureus beta operon.

PMID- 7729676
TI  - The origin of common laboratory mice.
AB  - The house mouse is one of the model organisms in genetics and more than 400
      inbred strains have been established. However, many of the strains are related
      and their ancestry can be traced back to European fancy mice inbred in the 1920s.
      Recent molecular studies corroborate the early historical records that assert
      that Japanese fancy mice were introduced into European stocks and thus
      contributed to the development of "old" inbred strains. Consequently, many inbred
      strains have genomic DNA derived from more than one subspecies of Mus musculus.
      The subspecific hybrid origin of common inbred strains has important bearings on
      the interpretation of genetic data, and the limitations that history imposes upon
      the currently available strains make it necessary to establish new inbred strains
      representing specific wild populations.

PMID- 7729677
TI  - A novel genetic interaction between daughterless and a variegating rearrangement
      strain of Drosophila melanogaster.
AB  - The effect of the maternal-effect mutation daughterless (da) on the reinverted
      In(1)BM2 strain of Drosophila melanogaster has been evaluated cytogenetically.
      Results show that while the variegated nature of the single X chromosome of
      In(1)BM2(rv) males born to female da/da x male +/+ parents is suppressed, their
      female sibs, homozygous for the In(1)BM2(rv) chromosome, survive the lethal
      effect of the absence of da+ product in their zygotes.

PMID- 7729678
TI  - The hyperactive X chromosome is not early replicating in mitotically active
      somatic cells of Drosophila nasuta males.
AB  - The temporal order of replication of the X chromosome(s) in mitotically dividing
      male and female cells in early embryos and in brain ganglia of Drosophila nasuta
      larvae was examined using [3H]thymidine pulse labelling and autoradiography. Both
      the X chromosomes in female cells and the single X chromosome in male cells
      replicated in complete synchrony with the autosome set in the nucleus. Thus,
      unlike the well-known early completion of replication by the hemizygous X
      chromosome in polytene nuclei in the salivary glands of male Drosophila larvae,
      the single X chromosome in mitotically dividing cells does not replicate earlier
      than the autosomes. We conclude that transcriptional hyperactivity of the single
      X chromosome required for dosage compensation in somatic cells of male Drosophila
      is not dependent upon its early replication.

PMID- 7729679
TI  - Pulsed-field gel analysis of 5S and satellite DNA in barley.
AB  - Pulsed-field gel electrophoresis was used to study the variability of clustered
      tandemly repeated sequences in barley. Twelve spring barley cultivars were
      investigated with a heterologous 5S DNA probe and the 118 base pair barley
      satellite DNA probe HVT01. On a per fragment basis, the 5S probe was 5 times and
      the barley satellite probe 6.7 times more variable than single- or low-copy RFLP
      markers, demonstrating their usefulness for cultivar distinction.

PMID- 7729680
TI  - Introgression analysis of an interspecific hybrid population in peanuts (Arachis
      hypogaea L.) using RFLP and RAPD markers.
AB  - Forty-six introgression lines (F10C9) from a cross between Arachis hypogaea L.
      (2n = 4x = 40) and A. cardenasii Krapov. & W. C. Gregory (2n = 2x = 20) were
      analyzed for the introgression of A. cardenasii chromosome segments. Seventy
      three RFLP probes and 70 RAPD primers, expressing from one to four A. cardenasii
      specific bands, were used to evaluate the set of introgression lines. Thirty-four
      RFLP probes and 45 RAPD primers identified putative A. cardenasii introgressed
      chromosome segments in one or more lines. Introgressed segments were detected by
      RFLP analysis in 10 of the 11 linkage groups; the smallest introgressed fragments
      were detected by single RFLP markers and the largest were detected by three or
      four adjacent markers and represented introgressed segments of 30-40 cM. Similar
      results were obtained with RAPD markers, although markers detecting introgressed
      fragments could not be placed on the peanut linkage map. Introgression into both
      A. hypogaea genomes was detected and its implication in breeding for disease
      resistance is discussed.

PMID- 7729681
TI  - Nucleotide sequence and genomic organization of cichlid fish minisatellites.
AB  - We have cloned, sequenced, and determined the genomic organization of
      minisatellites from the African cichlid fish, Oroechromis niloticus. We estimate
      that minisatellites related in sequence to the Jeffreys' core probes 33.6 and
      33.15 occur approximately every 1000 kilobase pairs in the cichlid fish genome.
      Sequencing of three minisatellites revealed that the size of the monomer units of
      the tandem arrays ranged from 7 to 24 base pairs (bp). One minisatellite appeared
      to contain a higher ordered periodicity of 90-120 bp superimposed on the apparent
      15 bp monomer repeat, indicating a particularly large unit of homogenization for
      a minisatellite array. Sequence heterogeneity of repeat units within tandem
      arrays varied considerably from one minisatellite to another. Hybridization of
      cloned minisatellites to genomic DNA of cichlid fishes generated, in most
      instances, multilocus fingerprint patterns, indicating that families of
      minisatellites related by sequence exist in the cichlid genome. Two minisatellite
      clones, however, generated polymorphic single locus fingerprints, suggesting that
      these loci are conserved in closely related African cichlids. The cross
      hybridization of these cichlid minisatellites within and between related taxa, as
      well as to unrelated fish species such as Atlantic salmon (Salmo salar),
      complement the human minisatellite sequences for the study of genetic
      relationships among individuals from a wide range of fish species.

PMID- 7729682
TI  - GATA- and GACA-repeats are not evenly distributed throughout the tomato genome.
AB  - This paper describes the distribution of highly polymorphic GATA- and GACA
      containing DNA regions in tomato. To study the distribution of these polymorphic
      regions, a mapping experiment was done. The segregation of 32 GATA- and GACA
      containing loci was analyzed in a F2 population from a cross between Lycopersicon
      esculentum and L. pennellii. From these loci, 28 could be mapped to 8 of the 12
      tomato chromosomes. Both the GATA- and GACA-containing loci seem to cluster in
      the same chromosomal regions. To our knowledge, this is the first report on
      mapping of GATA- and GACA-containing loci in plants.

PMID- 7729683
TI  - Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain
      structure and tissue distribution.
AB  - Progression through the cell cycle is catalyzed by cyclin-dependent kinases
      (CDKs) and is negatively controlled by CDK inhibitors (CDIs). We have isolated a
      new member of the p21CIP1/p27KIP1 CDI family and named it p57KIP2 to denote its
      apparent molecular mass and higher similarity to p27KIP1. Three distinct p57
      cDNAs were cloned that differ at the start of their open reading frames and
      correspond to messages generated by the use of distinct splice acceptor sites.
      p57 is distinguished from p21 and p27 by its unique domain structure. Four
      distinct domains follow the heterogeneous amino-terminal region and include, in
      order, a p21/p27-related CDK inhibitory domain, a proline-rich (28% proline)
      domain, an acidic (36% glutamic or aspartic acid) domain, and a carboxy-terminal
      nuclear targeting domain that contains a putative CDK phosphorylation site and
      has sequence similarity to p27 but not to p21. Most of the acidic domain consists
      of a novel, tandemly repeated 4-amino acid motif. p57 is a potent inhibitor of G1
      and S-phase CDKs (cyclin E-cdk2, cyclin D2-cdk4, and cyclin A-cdk2) and, to
      lesser extent, of the mitotic cyclin B-Cdc2. In mammalian cells, p57 localizes to
      the nucleus, associates with G1 CDK components, and its overexpression causes a
      complete cell cycle arrest in G1 phase. In contrast to the widespread expression
      of p21 and p27 in human tissues, p57 is expressed in a tissue-specific manner, as
      a 1.5-kb species in placenta and at lower levels in various other tissues and a 7
      kb mRNA species observed in skeletal muscle and heart. The expression pattern and
      unique domain structure of p57 suggest that this CDI may play a specialized role
      in cell cycle control.

PMID- 7729684
TI  - p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a
      candidate tumor suppressor gene.
AB  - Cyclin-dependent kinases (Cdks) are positive regulators of cell proliferation,
      whereas Cdk inhibitors (CKIs) inhibit proliferation. We describe a new CKI,
      p57KIP2, which is related to p21CIP1 and p27KIP1. p57KIP2 is a potent, tight
      binding inhibitor of several G1 cyclin/Cdk complexes, and its binding is cyclin
      dependent. Unlike CIP1, KIP2 is not regulated by p53. Overexpression of p57KIP2
      arrests cells in G1. p57KIP2 proteins have a complex structure. Mouse p57KIP2
      consists of four structurally distinct domains: an amino-terminal Cdk inhibitory
      domain, a proline-rich domain, an acidic-repeat region, and a carboxy-terminal
      domain conserved with p27KIP1. Human p57KIP2 appears to have conserved the amino-
      and carboxy-terminal domains but has replaced the internal regions with sequences
      containing proline-alanine repeats. In situ hybridization during mouse
      embryogenesis revealed that KIP2 mRNA displays a striking pattern of expression
      during development, showing high level expression in skeletal muscle, brain,
      heart, lungs, and eye. Most of the KIP2-expressing cells are terminally
      differentiated, suggesting that p57KIP2 is involved in decisions to exit the cell
      cycle during development and differentiation. Human KIP2 is located at 11p15.5, a
      region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a
      familial cancer syndrome, marking it as a candidate tumor suppressor. The
      discovery of a new member of the p21CIP1 inhibitor family with novel structural
      features and expression patterns suggests a complex role for these proteins in
      cell cycle control and development.

PMID- 7729685
TI  - Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset
      of Hox proteins.
AB  - The human proto-oncogene PBX1 codes for a homolog of Drosophila extradenticle, a
      divergent homeo domain protein that modulates the developmental and DNA-binding
      specificity of select HOM proteins. We demonstrate that wild-type Pbx proteins
      and chimeric E2a-Pbx1 oncoproteins cooperatively bind a consensus DNA probe with
      HoxB4, B6, and B7 of the Antennapedia class of Hox/HOM proteins. Specificity of
      Hox-Pbx interactions was suggested by the inability of Pbx proteins to
      cooperatively bind the synthetic DNA target with HoxA10 or Drosophila even
      skipped. Site-directed mutagenesis showed that the hexapeptide motif (IYPWMK)
      upstream of the Hox homeo domain was essential for HoxB6 and B7 to cooperatively
      bind DNA with Pbx proteins. Engraftment of the HoxB7 hexapeptide onto HoxA10
      endowed it with robust cooperative properties, demonstrating a functional role
      for the highly conserved hexapeptide element as one of the molecular determinants
      delimiting Hox-Pbx cooperativity. The Pbx homeo domain was necessary but not
      sufficient for cooperativity, which required conserved amino acids carboxy
      terminal of the homeo domain. These findings demonstrate that interactions
      between Hox and Pbx proteins modulate their DNA-binding properties, suggesting
      that Pbx and Hox proteins act in parallel as heterotypic complexes to regulate
      expression of specific subordinate genes.

PMID- 7729686
TI  - Cloning and characterization of a TFIIIC2 subunit (TFIIIC beta) whose presence
      correlates with activation of RNA polymerase III-mediated transcription by
      adenovirus E1A expression and serum factors.
AB  - TFIIIC2 is a general factor essential for transcription of 5S RNA, tRNA, and VA
      RNA genes by mammalian RNA polymerase III and consists of two forms designated
      TFIIIC2a and TFIIIC2b. TFIIIC2a and TFIIIC2b share common subunits of 220, 102,
      90, and 63 kD but differ with respect to transcription activity and the presence
      of a presumptive 110-kD subunit in the active form (TFIIIC2a). Because both forms
      can bind the promoter directly, a selective role for the 110-kD subunit in the
      regulation of RNA polymerase III activity has been suggested. To investigate this
      possibility, we have cloned and expressed a cDNA encoding the 110-kD subunit
      (TFIIIC beta). Immunoprecipitation studies with anti-TFIIIC beta antibodies have
      confirmed that TFIIIC beta is a bona fide subunit present only in TFIIIC2a, that
      TFIIIC2a and the general factor TFIIIC1 are associated in unfractionated
      extracts, and that previously undetected polypeptides (potential TFIIIC1
      subunits) can be isolated in association with TFIIIC2a. Previous studies have
      shown that increases in RNA polymerase III activity during infection of cells by
      adenovirus (with concomitant E1A expression) or during cell growth at high serum
      concentration results from an increased activity in the TFIIIC fraction. Studies
      with antibodies to TFIIIC beta have shown that this is strongly correlated with a
      selective increase in the cellular concentration of the TFIIIC beta 110-kD
      subunit and a concomitant rise in the ratio of the active-to-inactive forms of
      TFIIIC2.

PMID- 7729687
TI  - twist is required in head mesenchyme for cranial neural tube morphogenesis.
AB  - To understand the role of twist during mammalian development, we generated twist
      null mice. twist-null embryos died at embryonic day 11.5. Their most prominent
      phenotype was a failure of the cranial neural folds to fuse. Mutant embryos also
      had defects in head mesenchyme, somites, and limb buds. Chimera analysis
      suggested that head mesenchyme was required for cranial neural tube closure and
      that twist acted in a cell-autonomous manner in this tissue. In addition, in the
      head mesenchyme region of chimeras, twist-null cells were segregated from wild
      type cells, and in the forebrain they lacked mesenchymal characteristics. These
      results suggest that twist regulates the cellular phenotype and behavior of head
      mesenchyme cells that are essential for the subsequent formation of the cranial
      neural tube.

PMID- 7729688
TI  - The Rhizobium meliloti groELc locus is required for regulation of early nod genes
      by the transcription activator NodD.
AB  - The molecular chaperones related to GroEL (hsp60, cpn60) interact with partially
      folded proteins and appear to assist them to attain active and correctly folded
      conformation. They are required for cell viability but are probably more
      important for some processes than for others. Through a random genetic search to
      find loci that are required for expression of the Rhizobium meliloti nod
      (nodulation) genes, we isolated a mutant (B4) defective in luteolin-dependent
      activation of nod gene expression, and found it carries a Tn5 insertion within a
      chromosomal groEL gene (groELc) located just downstream of a groESc gene. The
      groELc mutation affected activity of three related LysR-type activator proteins
      NodD1, NodD3, and SyrM; on plants, the mutants formed nodules late, and the
      nodules were Fix-. Hybridization and protein expression analysis show that a
      similar groESL locus (groESLa) maps to the Rm1021 megaplasmid pSyma. Southern
      blot analysis revealed additional, but less closely related sequences hybridizing
      to groELc and groESc probes elsewhere in the R. meliloti genome. Clones of
      groESLc and groESLa can each restore robust phage lambda growth on an Escherichia
      coli groE mutant. Likewise each clone can complement all of the phenotypes
      observed for B4 mutants; thus, the two appear to be functionally equivalent if
      expression is controlled. We determined that groELc is required for normal DNA
      binding of the NodD target sequence in R. meliloti. GroEL coimmunopurifies with
      NodD1 from R. meliloti, which suggests a direct physical association between
      these proteins. GroEL is thus probably involved in the folding or assembly of
      transcriptionally active NodD.

PMID- 7729689
TI  - Drosophila MEF2, a transcription factor that is essential for myogenesis.
AB  - mef2 encodes the only apparent Drosophila homolog of the vertebrate myocyte
      specific enhancer factor 2 (MEF2). We show herein that the Drosophila MEF2
      protein is expressed throughout the mesoderm following gastrulation. Later in
      embryogenesis, its expression is maintained in precursors and differentiated
      cells of the somatic and visceral musculature, as well as the heart. We have
      characterized genetic deficiencies and EMS-induced point mutations that result in
      complete loss of MEF2 protein in homozygous mutant embryos. These embryos exhibit
      a dramatic absence of myosin heavy chain (MHC)-expressing myoblasts and lack
      differentiated muscle fibers. Examination of earlier events of muscle development
      indicates that the specification and early differentiation of somatic muscle
      precursors are not affected because even-skipped-, nautilus-, and beta 3-tubulin
      expressing myoblasts are present. However, these partially differentiated cells
      are unable to undergo further differentiation to form muscle fibers in the
      absence of mef2. The later aspects of differentiation of the visceral mesoderm
      and the heart are also disrupted in mef2 mutant embryos, although the
      specification and early development of these tissues appear unaffected. Midgut
      morphogenesis is disrupted in the mutant embryos, presumably as a consequence of
      abnormal development of the visceral mesoderm. In the heart, the cardial cells do
      not express MHC. These results indicate that MEF2 is required for later aspects
      of differentiation of the three major types of musculature, which include body
      wall muscles, gut musculature, and the heart, in the Drosophila embryo.

PMID- 7729690
TI  - MEK-2, a Caenorhabditis elegans MAP kinase kinase, functions in Ras-mediated
      vulval induction and other developmental events.
AB  - Activated Ras initiates a cascade of sequential phosphorylation events, including
      the protein kinases Raf, MEK, and MAP kinase. The Let-60 Ras-mediated signal
      transduction pathway controls vulval induction in Caenorhabditis elegans. Both
      Lin-45 Raf and Sur-1 MAP kinase have been determined to be essential factors
      during vulval induction; however, the C. elegans mek gene has not been
      identified. In this paper, we have cloned a C. elegans mek gene, mek-2, and
      demonstrated that the MEK-2 protein possesses the biochemical properties of MAP
      kinase kinases: The C. elegans MEK-2 protein can phosphorylate and activate a
      human MAP kinase (ERK1), and MEK-2 itself can be phosphorylated and activated by
      immunoprecipitated mammalian Raf. The mek-2 gene plays a key role in the let-60
      ras-mediated vulval induction pathway, as loss-of-function mutations in the gene
      (ku114 and h294) significantly reduce the signal transmitted through Ras. mek
      2(ku114) completely suppressed the Multivulva (Muv) phenotype of a hyperactive
      let-60 ras mutation, and animals homozygous for mek-2(ku114) also displayed a
      partial larval lethal phenotype. Animals homozygous for mek-2(h294) exhibited a
      highly penetrant sterile and Vulvaless phenotype. Microinjection of a gain-of
      function mek-2 mutation resulted in Muv and other mutant phenotypes, whereas
      microinjection of a dominant-negative mutation not only suppressed the Muv
      phenotype of an activated let-60 ras mutation but also caused an egg-laying
      defective phenotype in otherwise wild type animals. Our results demonstrate that
      mek-2 acts between lin-45 raf and sur-1/mpk-1 in a signal transduction pathway
      used in the control of vulval differentiation and other developmental events.

PMID- 7729691
TI  - The Caenorhabditis elegans gene mek-2 is required for vulval induction and
      encodes a protein similar to the protein kinase MEK.
AB  - An evolutionarily conserved signal transduction pathway that utilizes a receptor
      tyrosine kinase and a Ras protein mediates the induction of vulval cell fates in
      the nematode Caenorhabditis elegans. We sought new genes that function in this
      pathway by screening for suppressors of the Multivulva phenotype caused by a
      mutation that activates the let-60 ras gene. Seven such suppressor mutations
      defined a new gene involved in vulval induction. We named this gene mek-2,
      because its predicted protein product is most similar to MEK, a protein
      serine/threonine and tyrosine kinase. mek-2 mutations can be arranged in an
      allelic series. A probable null mutation eliminated vulval induction, and the
      strongest mutations alter codons conserved in most or all protein kinases. Our
      genetic analysis showed that mek-2 functions downstream of let-60 ras and is
      required for ras-mediated signal transduction in vivo. The MEK-2 protein may
      interact with the products of the lin-45 raf and mpk-1 MAP kinase genes, which
      also mediate vulval induction.

PMID- 7729692
TI  - Identification of a human specific Alu insertion in the factor XIIIB gene.
AB  - The factor XIIIB gene was examined to determine the nature of a previously
      described 300 bp restriction fragment length polymorphism (RFLP) seen in the
      human population. Polymerase chain reaction analysis of different regions within
      the factor XIIIB gene was carried out to define a high resolution map of the
      region encompassing the polymorphism, followed by DNA sequence analysis. An Alu
      insertion was found to be the source of this variation. This Alu repeat is a
      member of the human specific-1 (HS-1) subfamily, although one of the five
      diagnostic nucleotides is a cattarhine specific (CS) subfamily mutation,
      suggesting that it may represent an intermediate form in the evolution between
      these two subfamilies. Subsequently, we developed a PCR-based assay to detect the
      polymorphism, rendering it a more useful marker for genetic linkage studies and
      genome mapping. This insertion is also a valuable polymorphism for human
      population studies, as demonstrated by the large variations in allele frequencies
      seen in three population groups.

PMID- 7729693
TI  - A temperature-sensitive mutant of Escherichia coli with an alteration in
      ribosomal protein L22.
AB  - A temperature-sensitive, protein synthesis-defective mutant of Escherichia coli
      exhibiting an altered ribosomal protein L22 has been investigated. The
      temperature-sensitive mutation was mapped to the rplV gene for protein L22. The
      genes from the wild type and mutant strains were amplified by the polymerase
      chain reaction and the products were sequenced. A cytosine to thymine transition
      at position 22 of the coding sequence was found in the mutant DNA, predicting an
      arginine to cysteine alteration in the protein. A single cysteine residue was
      found in the isolated mutant protein. This amino acid change accounts for the
      altered mobility of the mutant protein in two-dimensional gels and during
      reversed-phase HPLC. The temperature-sensitive phenotype was fully complemented
      by a plasmid carrying the wild type L22 gene. Ribosomes from the complemented
      cells showed only wild type protein L22 by two dimensional gel analysis and were
      as heat-resistant as control ribosomes in a translation assay. The point mutation
      in the L22 gene is uniquely responsible for the temperature-sensitivity of this
      strain.

PMID- 7729694
TI  - Analysis of nucleotide substitutions and amino acid conservation in the
      Drosophila Adh genomic region.
AB  - The homologous genomic region that contains two paralogous genes, Adh and Adh
      dup, was compared in several Drosophila species. Sequences were analyzed as
      follows: a) At the nucleotide level, Ka and Ks values were determined for each
      pair of species. Ka-Adh and Ka-Adh-dup are not significantly different. However,
      Ks-Adh values are significantly lower than Ks-Adh-dup, which are more variable.
      In agreement with other reports, lower Ks values for Adh correlate with a high
      level of gene expression and relatively high percentage of G+C content in the
      third codon position, while the opposite applies to Adh-dup. b) At the protein
      level, amino acid comparisons reveal conserved regions shared by ADH and ADH-DUP,
      which have been assigned to known functional domains. Key residues for
      dehydrogenasic function are also found in ADH-DUP, thus pointing to a
      dehydrogenase activity for ADH-DUP, albeit very different from that of ADH.

PMID- 7729695
TI  - Phenotypic expression of ADH regulatory genes in Drosophila melanogaster: a
      comparative study between a paleartic and a tropical population.
AB  - In vitro ADH activity was studied in D. melanogaster males from two sets of third
      chromosome substitution lines, one from a paleartic population (Gigean, France),
      the other from a tropical population (Brazzaville, Congo). As a linear model with
      raw ADH activity dependent on fresh weight was significant in both sets of lines,
      the raw activity was adjusted by regression on weight. Two main results were
      found: (a) the well-known substantial intrapopulation variability; and (b) third
      chromosome geographical origin did not affect the mean ADH activity. Unlike the
      structural Adh gene polymorphism which allows the two populations to be
      distinguished, the polymorphism of the third chromosome ADH regulatory genes (or
      more exactly their phenotypic expression) does not allow to discriminate between
      them. These results are discussed in the context of the adaptation of D.
      melanogaster to the alcoholic substrates in light of a model proposed by Hedrick
      and McDonald (1980) in order to interpret variations in both structural and
      regulatory gene polymorphisms.

PMID- 7729696
TI  - Associations of esterase 6 allozyme and activity variation with reproductive
      fitness in Drosophila melanogaster.
AB  - Previous studies have shown that the esterase 6 (EST6) enzyme of D. melanogaster
      is mainly produced in the sperm ejaculatory duct of the adult male and
      comparisons of wild-type males with laboratory null mutants have suggested that
      the enzyme plays a role in reproductive fitness. In this study we have compared
      18 field-derived lines each isoallelic for Est6 for differences in five
      components of male reproductive fitness. No consistent fitness differences were
      found among lines differing in respect of the two major allozyme classes EST6-F
      and EST6-S, despite other evidence that these two classes are not selectively
      equivalent in the field. However, differences in reproductive fitness were found
      among lines differing in the minor mobility variants that segregate within EST6-F
      and EST6-S. A failure to distinguish among these minor forms may explain the
      discrepancies in previous studies on the effects of the major EST6 allozymes on
      reproductive fitness. The most significant associations we have found between
      EST6 and reproductive fitness were due to variation in EST6 activity levels. Male
      EST6 activity levels were found to be positively correlated with their time to
      first mating, negatively correlated with the numbers of eggs laid and progeny
      produced by their mates, and negatively correlated with the frequency with which
      their mates remate. We conclude that some EST6 variants differ in components of
      male reproductive fitness operative in laboratory cultures. However, the evidence
      for fitness differences is stronger for variants affecting the amount, rather
      than the structure of the enzyme, and the direction of the differences varies
      between some of the fitness components tested.

PMID- 7729697
TI  - Molecular evolution and population genetics of Greater Caribbean green turtles
      (Chelonia mydas) as inferred from mitochondrial DNA control region sequences.
AB  - The molecular evolution and population genetics of migratory green turtles
      (Chelonia mydas) in the Greater Caribbean were examined with mitochondrial DNA
      (mtDNA) control region I sequences. A total of 488 base positions (bp) per
      individual were aligned for 44 individuals from four nesting populations in
      Florida, Costa Rica, Aves Island (Venezuela), and Surinam. Twelve sequence
      polymorphisms were detected, representing ten transitions, one transversion, and
      one 10-bp repeat. Sequence analyses of within- and between-population diversity
      revealed a deep divergence between western and eastern Caribbean nesting colonies
      and an inverse relationship between reproductive female population size and mtDNA
      diversity. In small populations, genetic admixture was important to maintaining
      high diversity, whereas larger populations appear to have experienced historical
      bottlenecks or resulted from founder effects. Mitochondrial DNA sequences of the
      control region offer an order of magnitude greater resolution than restriction
      site data for addressing questions about mtDNA variation, both within and between
      populations of green turtles.

PMID- 7729698
TI  - rDNA site number polymorphism and NOR inactivation in natural populations of
      Allium schoenoprasum.
AB  - Nucleolar-organiser activity has been studied by silver staining and by in situ
      hybridization with an rDNA probe in two populations of Allium schoenoprasum. One
      population is monomorphic with NORs and rDNA sites terminal on the short arm of
      pair 8 in all individuals. The other populations is monomorphic for pair 8 NORs
      but is also polymorphic for NORs on the long arm of pair 7. All plants in this
      population carry ribosomal cistrons on both chromosomes of pair 7 but 0, 1 or 2
      of these sites can be active in rRNA synthesis. Cis-acting nucleolar-suppression
      affects the pair 7 locus. We suggest that there has been progressive reduction in
      the number of NORs during the evolution of A. schoenoprasum.

PMID- 7729699
TI  - Mitochondrial DNA from a spider mite: isolation, restriction map and partial
      sequence of the cytochrome oxidase subunit I gene.
AB  - Mitochondrial (mt) DNA of the phytophagous mite Tetranychus urticae was purified
      and a restriction map was constructed. The 12.5 kb long genome is the shortest
      animal mtDNA known. A 564 bp clone comprising part of the gene for cytochrome
      oxidase subunit I was sequenced. As has been found in insects, the mitochondrial
      sequences of mites are extremely A+T rich (75% on average, 96.5% at the third
      codon position).

PMID- 7729700
TI  - Satellite DNA sequences flank amplified DHFR domains in marker chromosomes of
      mouse fibrosarcoma cells.
AB  - This study centers on marker chromosomes carrying expanded chromosomal regions
      which were observed in two independent derivatives of the AA12 murine
      fibrosarcoma line, the 10(-3) M MTX-res H2 and the 5 x 10(-7) M MTX-res E.
      Previous characterization of the marker chromosomes of MTX-res variants showed
      their common derivation from a marker chromosome (m) of the parental line,
      endowed with two interstitial C-bands. Cytogenetic evidence pointed to one C-band
      of m as the site involved in the chromosomal rearrangements leading to the
      HSR/ASR chromosomes. ISH of a 3H-labeled satellite DNA probe allowed satellite
      sequences flanking the HSR/ASR in the marker chromosomes, where the C-band was no
      longer visible, to be detected. FISH experiments using biotinylated DHFR and
      satellite DNA probes showed that the respective target sequences are contiguous
      in new marker chromosomes. They also allowed inter- and intrachromosomal
      rearrangements to be seen at DHFR amplicons and satellite sequences. Double-color
      FISH using digoxygenated satellite DNA and biotinylated pDHFR7 showed that in a
      marker chromosome from the H2 cell line the two target sequences are not only
      adjacent, but closer than 3 Mb, as indicated by overlapping of the different
      fluorescence signals given by the two probes. Another marker chromosome in the E
      variant was shown to display a mixed ladder structure consisting of a head-to
      head tandem of irregularly-sized satellite DNA blocks, with two symmetrical
      interspersed DHFR clusters.

PMID- 7729701
TI  - Enzymatic digestion increases permeability of the outer blood-retinal barrier for
      high-molecular-weight substances.
AB  - BACKGROUND: The purpose of the study was to investigate whether lysosomal enzymes
      can participate in damaging the outer blood-retinal barrier and to examine the
      role of glycosaminoglycans in maintaining the barrier function for high-molecular
      weight substances. METHODS: The ciliary artery was cannulated in freshly
      enucleated pig eyes. Perfusion was performed with buffer (controls), with
      heparinase (substrate: heparan sulfate), or with lysosomal enzymes freshly
      prepared from pig retinal pigment epithelium at 36 degrees C, followed by
      perfusion with the tracer native ferritin (NF) or the marker cationized ferritin
      (CF). The eyes were examined by electron microscopy. RESULTS: In controls treated
      with buffer alone, NF was found in high concentration in the lumina of the
      choroidal capillaries; however, little NF was found in Bruch's membrane (BsM).
      The tracer did not penetrate to any extent beyond BsM. In eyes digested with
      heparinase or lysosomal enzymes, significantly higher numbers of tracer molecules
      were found in BsM. Furthermore, NF penetrated BsM and was apparent in the
      subretinal space and also inside retinal pigment epithelial cells, probably due
      to pinocytosis. CONCLUSIONS: The results indicate that heparan sulfate
      proteoglycan is important for the maintenance of the outer blood-retinal barrier
      and that lysosomal proteases may participate in damaging this barrier, causing
      increased permeability to high-molecular-weight substances.

PMID- 7729703
TI  - Detection of retinal arterial macroaneurysms with indocyanine green
      videoangiography.

PMID- 7729702
TI  - A model for pulsatile and steady ocular blood flow.
AB  - BACKGROUND: The aim was to elucidate two controversial questions. (1) is the
      pulsatile inflow dominant or is there a sizeable steady inflow component? (2) Is
      the outflow of blood steady or pulsatile in induced and in glaucomatous
      hypertension? METHODS: The OBF system (Langham) was used for pulse recording. A
      simple electric flow model was conceived and analysed in terms of Fourier series,
      using linear circuit theory. RESULTS AND CONCLUSIONS: Possible explanations of
      the seemingly inconsistent observations are indicated by the model. (1) A steady
      inflow of similar magnitude to the pulsatile one is predicted. The total flow can
      be determined at present theoretically from recordings of the pulsatile inflow
      and of the systolic and diastolic intraocular blood pressure. Some methodological
      improvements are desirable in order to obtain reliable estimates in practice. (2)
      The outflow is normally steady, probably even in ocular hypertension and
      glaucoma. In hypertension induced with the suction cup this may be doubted. The
      eye has similarities with the device called the Starling resistor which describes
      the behaviour of collapsible vessels. Acute pressure increase (plus the
      pulsations of the IOP) may put the collapsible vessels into a state which
      disturbs the steady outflow. The effects of changes in IOP and in other
      components on the size and shape of the flow curve are demonstrated.

PMID- 7729704
TI  - Biochemical studies of glycosaminoglycans in nanophthalmic sclera.
AB  - BACKGROUND: Since Brockhurst reported the connection between uveal effusion in
      nanophthalmic eyes and their scleral alterations and treated them with vortex
      vein decompression or sclerectomy, many observers have found abnormal
      accumulation of glycosaminoglycans (GAGs) in nanophthalmic sclera. These GAG
      abnormalities were thought to effect the collagen changes, though it was not
      clear which GAGs were changed. METHODS: GAGs were isolated and their contents
      were determined in scleral specimens from three nanophthalmic patients and five
      age-matched controls, using electrophoresis and the cetylpyridinium method.
      RESULTS: Hyaluronic acid, dermatan sulfate and chondroitin sulfate were the major
      GAGs in both nanophthalmic and control samples. Nanophthalmic sclera showed 2.4
      fold, 10-fold and 5.5-fold increases in hyaluronic acid, dermatan sulfate and
      chondroitin sulfate, respectively, compared with the controls. CONCLUSION: The
      results suggest that increased levels of GAGs, particularly of dermatan sulfate
      and chondroitin sulfate may contribute to the abnormalities of collagen
      fibrillogenesis and be closely involved with the pathogenesis of nanophthalmos.

PMID- 7729705
TI  - Lens capsule opacification in aphakic and pseudophakic eyes.
AB  - BACKGROUND: Posterior capsule opacification (PCO) is the most common complication
      of lens extraction. Although intraocular lenses (IOLs) are thought to inhibit
      capsule opacification, the mechanisms by which they do this are poorly
      understood. This study was done to determine the effects of pseudophakia on
      secondary cataract and PCO in experimentally lentectomized dogs. METHODS: Twenty
      four normal dogs were bilaterally lentectomized by phacoemulsification and
      unilaterally implanted with a plano-convex polymethylmethacrylate IOL. Secondary
      cataracts and capsule opacification were evaluated at weeks 1, 2, 4, 10, 14, and
      20 after surgery by retrolillumination photography, light microscopy, and
      scanning and transmission electron microscopy. RESULTS: The pattern of secondary
      cataract and PCO in dogs was found to be similar to that in other animal species.
      Production of new lens material was prominent in the equatorial region, and PCO
      resulted from fibrous metaplasia of lens epithelium and subsequent capsular
      fibrosis and wrinkling. The presence of an IOL did not prevent the posterior
      migration of epithelium, nor did it prevent fibrous metaplasia. The presence of
      an IOL did, however, minimize the capsule-wrinkling effects of fibroplasia and
      limit the space available for lentoid formation. CONCLUSION: In pseudophakic
      eyes, IOLs influence secondary cataract formation by limiting the space available
      for lentoid formation and by maintaining a linear scaffolding for lens epithelial
      fibrous metaplasia.

PMID- 7729706
TI  - Anterior chamber inflammation after transconjunctival cryosurgery.
AB  - BACKGROUND: Inflammation caused by transconjunctival cryotherapy for prophylactic
      retinal detachment surgery was measured in various conditions. METHODS: Thirty
      four eyes of 28 patients with peripheral retinal lesions predisposing to retinal
      detachment were studied by laser flare cell meter before and after treatment.
      RESULTS: The mean flare value for 34 eyes was 4.06 +/- 1.45 photon counts/ms
      before surgery and 5.72 +/- 2.52 pc/ms after surgery (p < 0.05). Flare value was
      elevated at 1, 2, and 3 weeks after treatment, peaking at 2 weeks (p < 0.05), and
      normal again at 4 weeks. There were no significant differences in flare increase
      between eyes with and without retinal breaks, eyes with and without limited
      retinal detachment, eyes with myopia more and less than -8.0 D, and eyes with a
      treatment area limited to one quadrant and extending over more than one quadrant.
      CONCLUSION: Transconjunctival cryosurgery caused mild inflammation in the
      anterior chamber of the eye for 3 weeks. The inflammation was not affected by the
      presence of retinal break or limited retinal detachment, the degree of myopia, or
      the extent of the treatment area.

PMID- 7729707
TI  - Schisis-like rhegmatogenous retinal detachment associated with choroidal
      colobomas.
AB  - BACKGROUND: The breaks that cause retinal detachments in colobomatous eyes are
      often hidden within the lesion and difficult to find. METHOD: To elucidate the
      pathoanatomy and possible pathomechanism of such detachments, histological
      sections of eight choroidal colobomas were reviewed. RESULTS: Sections of the
      margin showed central continuation of the inner neuroblastic layer (the
      intercalary membrane) and eversion and separation of the outer neuroblastic
      layer. The opposite direction of continuity of the neuroblastic layers created a
      schisis-like configuration between the intercalary membrane and the everted outer
      retina. The zone of duplication was a point of retinal adhesion, but also a locus
      minoris resistentiae due to vitreous attachments and variable glial support at
      the margin. CONCLUSION: The subset of coloboma-associated retinal detachments
      requires both a central break in the inner layer and a break in the outer layer
      at the margin of the coloboma. The inner layer break may be precipitated by
      retinovascular ischemia or scleral stretching; that in the outer layer may be
      caused by vitreous traction on the margin of the coloboma or extension of the
      formerly isolated detachment through the outer marginal zone of decreased glial
      support.

PMID- 7729709
TI  - The radiosensitivity of uveal melanoma cells and the cell survival curve.
AB  - BACKGROUND: No study of the radiosensitivity of uveal melanoma cells and their
      survival curve has been published. The purpose of this study was to investigate
      the sensitivity to different single radiation doses of SP6.5, a human uveal
      melanoma cell line. METHODS: Cells were irradiated with cobalt-60 at doses from 0
      to 1200 cGy. Radiosensitivity was measured by three methods: soft-agar bilayer
      assay, tritiated thymidine incorporation, and bromodeoxyuridine (BrdU)
      incorporation. RESULTS: The soft-agar bilayer assay, by assessing the colony
      forming units, showed that the D1 value was 470 cGy, the Dq value was 400 cGy,
      and the n value exceeded 10, thus indicating a broad, shoulder and relative
      radioresistance. The doubling time as estimated by [3H]thymidine incorporation
      was unaffected at doses below 600 cGy, another indication of radioresistance.
      BrdU incorporation revealed no significant increase between 0 and 1000 cGy,
      indicating that the cell cycle was not interrupted. CONCLUSION: Cell survival,
      doubling time, and cell phases are parameters of growth kinetics, and the results
      suggest that SP6.5 is radioresistant and virtually unaffected by single radiation
      doses lower than 600 cGy. Our data parallel published data for cutaneous
      melanomas.

PMID- 7729708
TI  - A comparison of colour Doppler imaging of orbital vessels and other methods of
      blood flow assessment.
AB  - BACKGROUND: Comparison of the haemodynamic measurements obtained by colour
      Doppler imaging and other methods of ocular blood flow measurements was desired.
      METHODS: The blood velocity findings from colour Doppler imaging of patients with
      central retinal vein occlusion were compared to the results of fluorescein video
      angiography, continuous tonography and ophthalmodynamometry. RESULTS: Patients
      with low or undetectable blood velocities in the central retinal vein had longer
      retinal dye transit times on fluorescein video-angiography. Tonography showed a
      positive correlation with the velocities in the ophthalmic artery, but
      ophthalmodynamometry showed a negative correlation with these velocities.
      CONCLUSION: The relationships between the blood velocities in orbital vessels and
      other blood flow measurements emphasise that there is a complex interaction of
      the blood flow parameters. Care must therefore be taken when interpreting the
      results of studies.

PMID- 7729710
TI  - The effect of thalidomide and supidimide on endotoxin-induced uveitis in rats.
AB  - BACKGROUND: Endotoxin-induced uveitis (EIU) is an animal model of ocular
      inflammation, produced by footpad injection of endotoxin (lipopolysaccharide,
      LPS) to mimic the human disease of acute anterior uveitis, that is useful for
      testing new anti-inflammatory therapy. The purpose of this study was to test the
      anti-inflammatory effect on EIU of thalidomide and one of its derivatives,
      supidimide. METHODS: EIU was produced in rats by hind foot-pad injection of LPS
      (100 micrograms/animal). Animals were killed 20 h after LPS injection.
      Inflammation was evaluated by anterior chamber determination of proteins and
      cells. RESULTS: A dosage of 400 mg/kg per day of thalidomide was efficient in
      reducing inflammation whether given in three doses (at -24 h, -4 h and +4 h
      relative to LPS challenge = THAL-1; p < 0.001 for proteins and cells), in two
      doses (-4 h and +4 h = THAL-2; p < 0.001 for proteins, p < or = 0.012 for cells)
      or in one dose (at +4 h = late THAL; p < 0.001 for proteins, p < or = 0.02 for
      cells). A dosage of 300 mg/kg per day of thalidomide was still efficient (p < or
      = 0.023 for proteins, p < or = 0.06 for cells), but 150 mg/kg per day had no
      effect on inflammation. Supidimide (400 mg/kg per day) had some anti-inflammatory
      effect (p < or = 0.053 for proteins, p < or = 0.06 for cells). CONCLUSION: High
      dose thalidomide had a potent anti-inflammatory effect in EIU, but lower doses
      were not sufficient to reduce inflammation. At similar high doses, supidimide had
      some effect on EIU but was less effective than thalidomide.

PMID- 7729712
TI  - [Morphology of the neuroendocrine-immunologic network of connective tissue in
      rodent fetal development].
AB  - Multi-range neuro-endocrine-immunological function in regulation of body
      homeostasis gives reasons for establishment of peripheral morphological bonds. As
      a result from our study, the unit of trophic protection of pelvic connective
      tissue was identified in embryonal and fetal development of rodents. This unit
      connects blood vessels and their autonomic innervation with chromaffin cells,
      mast cells, and simple neurons. Nerve fibres of para-organ pelvic ganglions
      determine to complete. Author suggestion on integration of another connective
      tissue cells and erythroid cells with systemic network requires verification.

PMID- 7729711
TI  - Mediators of the ocular inflammatory response to interleukin-1 beta plus tumor
      necrosis factor-alpha.
AB  - BACKGROUND: Intravitreal injection of marginally inflammatory doses of
      interleukin-1 beta and tumor necrosis factor-alpha (IL-1 beta/TNF alpha) has been
      shown to produce intraocular inflammation distinctly different from that induced
      by higher intravitreal doses of either IL-1 or TNF alpha. Since cyclooxygenase
      inhibitors and platelet-activating factor (PAF)-receptor antagonists can reduce
      IL-1- or TNF alpha-induced uveitis, the present investigation was undertaken to
      determine whether cyclooxygenase metabolites of arachidonic acid and PAF are
      important mediators of IL-1 beta/TNF alpha-induced uveitis. METHODS: The
      cyclooxygenase inhibitor indomethacin and two structurally dissimilar PAF
      receptor antagonists, SRI 63-441 and WEB 2086, were used to investigate the
      importance of cyclooxygenase metabolites and PAF in IL-1 beta/TNF alpha-induced
      uveitis. RESULTS: Based upon the effectiveness of indomethacin, the anterior
      uveitis induced by IL-1 beta/TNF alpha could be divided into two phases; a
      primary phase dependent upon generation of cyclooxygenase metabolites (the first
      24 h) and a secondary phase largely independent of cyclooxygenase metabolite
      production (24-48 h). Posterior uveitis was also apparent at 48 h and was reduced
      by indomethacin. SRI 63-441 reduced the anterior uveitis at 24 h and to a lesser
      extent at 48 h; it also reduced the posterior uveitis at 48 h. However, although
      WEB 2086 was as effective as SRI 63-441 in reducing PAF-induced platelet
      aggregation, ex vivo, it did not significantly reduce IL-1 beta/TNF alpha-induced
      uveitis. CONCLUSIONS: Although the findings do not support an important role for
      PAF in TNF alpha/IL-1 beta-induced uveitis, it cannot be ruled out that more
      intensive treatment with a specific and long-acting PAF-receptor antagonist might
      yield more positive results.

PMID- 7729713
TI  - [The influence of perinatal asphyxia on the occurrence of respiratory distress
      syndrome in preterm labor].
AB  - During the period 1985-1992, the influence of perinatal asphyxia on the frequency
      of RDS was investigated in preterm neonates. Two thousand one hundred and sixty
      eight premature infants born alive without congenital malformations weighing from
      900 g to 2500 g were in the investigated group. The frequency of the occurrence
      of RDS and its most severe form--hyaline membrane disease (HMD)--was evaluated
      depending on state at birth in the first and fifth minute of life. The clinical
      diagnosis of HMD was verified during the postmortem examination. The state at
      birth was evaluated using Apgar score. In the statistical analysis, the F
      Snedecor variance test was used. During this study, the influence of perinatal
      asphyxia on the occurrence of RDS, and particularly its most severe form--HMD,
      was evaluated.

PMID- 7729714
TI  - [Autoimmune thrombocytopenia in pregnant women: diagnosis, treatment and
      prevention of complications in children].
AB  - 9 pregnancies (in 6 women) complicated by autoimmune thrombocytopenia were
      studied. Corticosteroids and/or azathioprine and/or intravenous immunoglobulins
      (IgG i.v.) were administered to 5 women during pregnancy. 1 complete remission
      (CR) was achieved after 3 mo. of treatment by corticosteroids and azathioprine.
      In peripartum period the treatment was administered in 7 cases (corticosteroids,
      IgG i.v., platelet transfusion). There were no haemorrhagic complications during
      peripartum period (8 vaginal delivery, 1 cesarean section). In 3 of 5 examined
      cases IgG antiplatelet antibody was detected. Study group was to small to define
      the correlation between level of antiplatelet antibodies and neonatal
      thrombocytopenia. 10 infants were born. 4 infants (including siblings) were found
      to have normal platelet counts immediately after delivery. They mothers were
      treated by IgG i.v. in 2 cases and 1 women in CR at the time of delivery. 4
      infants were thrombocytopenic but required no treatment. Duration time of
      thrombocytopenia was 1 to 4 weeks. In these cases mothers were treated only by
      corticosteroids or had no therapy.

PMID- 7729715
TI  - [An evaluation of agreement between cytologic, colposcopic and histologic results
      in neoplasms of the uterine neck].
AB  - There was carried out a retrospective analysis of cytologic, and colposcopic
      examination results in a group of 748 women with diagnosed cervical
      intraepithelial neoplasia (CIN) basing on histologic examinations of topical
      biopsy samples. In the CIN III group, in addition, results of preoperative
      histologic examinations were compared with those of postoperative histologic
      examinations. The examinations showed that a complex CIN diagnosis, including
      cytologic and colposcopic examination combined with taking topical biopsy samples
      achieves high accuracy and makes surgical conization a safe medical procedure in
      such cases. Histologic examination of the postoperative material determines
      further (follow-up) procedures.

PMID- 7729716
TI  - [Human papilloma virus (HPV) infections of the uterine cervix, vagina and vulva
      in women of childbearing age].
AB  - An analysis of the frequency of HPV infections and their clinical course within
      the uterine cervix, vagina and vulva with regard to the intraepithelial neoplasia
      in pregnant and non pregnant women was performed. The material consists of 484
      women (181 pregnant and 303 non pregnant women). The evaluation of a clinical
      course of overt and subclinical HPV infection was carried out in 47 pregnant and
      34 non pregnant women. In the group with CIN concomitant HPV infection concerned
      71.4% of pregnant and 61.4 of non pregnant women. In the group without CIN in
      4.8% was found subclinical form and in 2.0% latent form of HPV infection in
      pregnant and accordingly in 4.6% and 6.0% of non pregnant women. In pregnant
      women in comparison with non pregnant patients overt form of HPV infections was
      observed more frequently. Pregnancy seems to have no effect upon the frequency of
      HPV infections of the cervix, vagina and vulva. On the other hand it modifies the
      development and course of the infections.

PMID- 7729717
TI  - [Lipid mobilizing activity in blood serum during the follicular and luteal phases
      of the menstrual cycle].
AB  - The lipid mobilising activity of woman's blood serum in the follicular and luteal
      phases has been investigated. This activity was determined according to the
      Buckle method concerning parametrial adipose tissue of female rats. It was found
      to enhance the lipid mobilising activity in the follicular phase of the menstrual
      cycle. The increment of the lipid mobilising activity in the luteal phase was
      lower than in the follicular phase.

PMID- 7729718
TI  - [Use of an GnRH analogue for induction of gonadotrophin ovulatory surge in cycles
      stimulated with clomiphene citrate and menopausal gonadotropin in an in vitro
      fertilization program].
AB  - In 23 women treated for sterility by the in vitro fertilization method the
      gonadotropins ovulatory surge was stimulated by applying a GnRH analogue
      (Buserelin). The authors showed that a single injection of GnRH analogue in the
      cycles stimulated with clomiphene citrate and menopausal gonadotropin causes
      pituitary output of both LH and FSH which is sufficient for morphological and
      functional maturity of the oocytes. After such treatment two patients conceived
      and delivered healthy babies.

PMID- 7729719
TI  - [Activity of cathepsin B and D in blood serum of women with uterine cervix
      neoplasms].
AB  - The activity of cathepsins B and D were determined in the serum in 98 patients
      with carcinoma of the cervix uteri and in 25 women with dysplasia of the cervix
      uteri. The clinical value of the examined enzymes was performed. The results show
      that the mean serum activity of cathepsins increase with progression of
      neoplastic disease. The elevation of at least one of two studied lysosomal
      hydrolases were estimated in 68 patients (69.5%) with carcinoma of the cervix
      uteri.

PMID- 7729720
TI  - [Insulin resistance in the pathogenesis of polycystic ovarian disease (PCOD)].
AB  - In polycystic ovarian disease there is a strong association between
      hyperinsulinemia and hyperandrogenism but not with obesity alone. The magnitude
      of peripheral insulin resistance is similar to that seen in non-insulin-dependent
      diabetes mellitus. Mild hyperinsulinemia in PCOD patients is not impair the
      carbohydrate metabolism. The elimination of the cause of hyperandrogenism by
      bilateral oophorectomy, long-acting Gn-RH agonist or antiandrogen cyproterone
      acetate did not improve the associated insulin resistance. In opposition to
      insulin resistance in the tissues responsible for metabolism of carbohydrate, the
      ovary remains sensitive to the effects of pancreatic hormone. Presumably this
      mechanism involved the interaction with IGF-I receptors to stimulate thecal and
      stromal androgen production. Insulin may sensitize the stroma to the stimulatory
      effect of LH. In the mechanism of follicular arrest take part increased level of
      binding proteins for IGF-I, mainly IGFBP 2, -4 and 5 inhibit FSH and IGF-I
      action.

PMID- 7729721
TI  - [Uterine papillary serous carcinoma].
AB  - Two cases of uterine papillary serous carcinoma are presented. Attention to
      propensity for deep myometrial invasion, upper abdominal spread and high relapse
      rate are paid. Patients require combined treatment.

PMID- 7729722
TI  - [Local coagulation confined to the uterus and adnexa--case description].
AB  - The seldom occurring local intravascular coagulation confined to the uterus and
      adnexa is described. The authors give attention on diagnostic difficulties in
      described case.

PMID- 7729723
TI  - The British Society of Gastroenterology spring meeting. Manchester, 5-7 April
      1995. Abstracts.

PMID- 7729724
TI  - Adjuvant treatment for endometrial cancer: who needs it?

PMID- 7729725
TI  - Good outcome associated with a standardized treatment protocol using selective
      postoperative radiation in patients with clinical stage I adenocarcinoma of the
      endometrium.
AB  - In 1982, a treatment protocol was instituted for the management of patients with
      clinical stage I adenocarcinoma of the endometrium. All pertinent historical,
      operative, and pathologic findings were reviewed by a multidisciplinary committee
      and 384 patients were prospectively assigned to either high- or low-risk
      categories. Patients were excluded from the study if they had clinically apparent
      extrauterine disease, clear cell or serous histologies, or microscopic ovarian
      metastasis. Patients were considered high-risk if they had one or more of the
      following factors: grade 3 tumor differentiation, myometrial invasion > 50% of
      the total wall thickness, pathologic cervical involvement, or adenosquamous
      histology. Two-hundred twenty-seven (59%) low-risk patients were followed without
      further treatment after surgery, while pelvic radiation was recommended for 157
      (41%) high-risk patients. The 5-year relapse-free survival rates in the low- and
      high-risk groups were 95 and 81%, respectively. There were no treatment-related
      deaths. Severe or life threatening chronic radiotherapy complications occurred in
      6 (5%) patients. Multivariate Cox analysis identified the following significant
      prognostic factors: grade, myometrial invasion, cervix involvement, and age. This
      treatment protocol represents a safe and effective method of managing patients
      with carcinoma of the endometrium and spares the need for radiation therapy in
      the low-risk patient.

PMID- 7729726
TI  - Surgical treatment of patients with stages IB and IIA carcinoma of the cervix and
      palpably positive pelvic lymph nodes.
AB  - Review of the records of all patients undergoing radical hysterectomy for
      cervical cancer at our institution between 1956 and 1985 revealed 121 patients
      with stage IB or IIA lesions and metastasis to pelvic lymph nodes. A uniform part
      of our surgical practice is to record the findings from visual and palpatory
      examinations of the intra-abdominal and retroperitoneal structures at the
      beginning of the operative report. This information was available for 117 of 121
      patients. Of these 117 patients, 51 (44%) had pelvic lymph nodes palpably
      involved with metastatic malignant disease at the time of exploration. The Kaplan
      Meier estimate of 5-year disease-free survival for this group was 40% (median
      follow-up of disease-free patients was 20.5 years). Adjuvant pelvic radiotherapy
      was received by 29 of the 51 patients. The remaining 22 patients received no
      adjuvant treatment. Information on the sites of recurrence was available for 30
      of 32 patients who had recurrence. The site of first recurrence included an
      extrapelvic component in 22 of the 30 (73%). Disease-free survival rates for
      these patients reflect the advanced nature of their tumors. In light of our
      experience and our current understanding of the relationship between radiotherapy
      dose, tumor volume, and efficacy, we regard the assertion that primary
      radiotherapy is preferable to surgery in this population to be counterintuitive,
      and we await with interest data demonstrating that disease-free survival with
      approaches that involve leaving macroscopic tumor on the pelvic sidewall is
      superior to that noted above.

PMID- 7729727
TI  - Management and follow-up of patients with adenocarcinoma in situ of the uterine
      cervix.
AB  - Management of adenocarcinoma in situ (ACIS) of the uterine cervix is
      controversial and cervical conization has been proposed as conservative
      management in patients desirous of future fertility. The efficacy of conization
      as treatment for cervical ACIS is unproven, as is the ideal method of follow-up.
      The purpose of this study was to assess the adequacy of conization of the cervix
      as conservative management of ACIS, and to assess the ability to detect recurrent
      disease. Between January 1964 and August 1993, 28 patients with a diagnosis of
      ACIS made by cone biopsy were seen at Memorial Sloan-Kettering Cancer Center.
      Initial management was as follows: total abdominal hysterectomy, 11 (39%);
      radical hysterectomy, 2 (7%); repeat conization, 6 (21%); and close follow-up, 9
      (32%). Of the 8 patients with positive margins who underwent a repeat cone biopsy
      or hysterectomy, 3 had residual ACIS in the subsequent surgical specimen and 1
      patient was diagnosed with invasive adenocarcinoma. Four of 10 (40%) patients
      with negative margins who underwent hysterectomy or repeat cone biopsy had
      residual ACIS. In addition, one patient whose cone margins were inevaluable was
      found to have invasive adenocarcinoma in a repeat conization specimen. Fifteen
      patients were managed conservatively with repeat conization of the cervix or
      close follow-up. Seven of 15 (47%) have had a recurrent glandular lesion detected
      after conization; 2 of these recurrences have been invasive adenocarcinoma. Since
      ACIS is not reliably diagnosed by cervical cytology and colposcopy, patients
      undergoing conservative management have been typically followed by endocervical
      curettage (ECC) in combination with Papanicolaou smear. In our series, the ECC
      was positive in only 43% of patients with glandular lesions prior to conization
      of the cervix. This retrospective study raises questions about the safety of
      therapeutic conization as conservative management of patients with ACIS of the
      uterine cervix and also highlights the potential inadequacy of following patients
      with Pap smears in combination with ECC.

PMID- 7729728
TI  - Paclitaxel: a radiation sensitizer of human cervical cancer cells.
AB  - Paclitaxel is an exciting chemotherapeutic agent active in a variety of malignant
      tumors. This study was designed to explore the radiosensitizing potential of
      paclitaxel in human cervical cancer cell lines. The cell lines ME180, SiHa, and
      MS751 were evaluated. Experiments were performed in the proliferative phase of
      growth. Paclitaxel doses were treated at 0.01x, 0.02x, 0.03x, 0.04x, and 0.05x
      peak plasma concentration (PPC) in ME180 and 0.001x, 0.002x, 0.003x, 0.004x, and
      0.005x PPC in SiHa and MS751. Radiation (RT) doses of cobalt-60 were 0, 2, 4, 6,
      8, and 10 Gy. In the combination group RT was given 48 hr after paclitaxel
      treatment. To allow for median effect analyses, combination doses were kept at a
      fixed ratio: 0.01x/2 Gy, 0.02x/4 Gy, 0.03x/6 Gy, 0.04x/8 Gy, and 0.05x/10 Gy for
      ME180 and 0.001x/2 Gy, 0.002x/4 Gy, 0.003x/6 Gy, 0.004x/8 Gy, and 0.005x/10 Gy in
      MS-751 and SiHa. Adenosine triphosphate bioluminescence was performed on Day 7
      after treatment and compared to untreated controls. Dose-response data were fit
      to the linear quadratic model and mean inactivation dose D was calculated. Data
      analysis with t test was performed. The median effect principle was used to
      evaluate the nature of the interaction between the two therapeutic modalities.
      Paclitaxel increased radiation cytotoxicity in all three cell lines. Mean
      inactivation D values for RT versus combination were 6.70 (+/- 0.15) and 4.33 (+/
      0.43) (P = 0.004) in ME180, 6.08 (+/- 0.70) and 4.54 (+/- 0.093) (P = 0.033) in
      MS751, and 7.03 (+/- 0.46) and 5.97 (+/- 0.51) (P = 0.034) in SiHa. The
      interaction of paclitaxel and RT was found to be supraadditive in ME180 and SiHa
      and subadditive in MS751. We conclude that paclitaxel has modest radiation
      sensitizing effects in cervical cancer cell lines and that further clinical
      trials should be considered.

PMID- 7729729
TI  - Associations between oncogenic human papillomaviruses and local invasive patterns
      in cervical cancer.
AB  - The polymerase chain reaction (PCR) was used to detect human papillomavirus (HPV)
      DNA in Formalin-acetic acid alcohol (FAA)-fixed paraffin-embedded tissue from 40
      patients whose primary cervical cancers showed a tentacular pattern of invasion
      at their advancing edges, and 40 patients (matched by age, International
      Federation of Obstetrics and Gynecology (FIGO) stage and histology type) whose
      tumors showed broad front invasion. The rate of HPV DNA positivity was the same
      in both the tentacular and the broad front tumors (83%), but the ratios of HPV 16
      to HPV 18 in the two groups were markedly different (20:10 versus 27:4,
      respectively). HPV type 18 was detected more frequently in tentacular than broad
      front tumors (P = 0.03). The overall rates of recurrence and mortality were 15
      and 9%, respectively (18 and 10% in the tentacular group compared with 13 and 8%
      in the broad front group). Univariate analysis showed statistically significant
      associations between HPV 18 and tumor recurrence (P = 0.04), but not between a
      tentacular pattern of invasion and tumor recurrence (P < 0.05). The findings to
      emerge from this survey indicate that the presence of particular HPV types may,
      in part, mediate the histological and clinical behavior of cervical cancers.

PMID- 7729730
TI  - Monitoring cancer antigen 125 levels in induction chemotherapy for epithelial
      ovarian carcinoma and predicting outcome of second-look procedure.
AB  - A retrospective analysis of 45 patients with epithelial ovarian carcinoma who
      underwent second-look procedure after initial cytoreduction and platinum-based
      combination chemotherapy was undertaken. Each patient was evaluated for the
      result of CA 125 after a third course of chemotherapy, the result of CA 125 prior
      to second-look laparotomy, and the calculated slope of regression curve for CA
      125. These results were compared for a normal value of CA 125 of < 35 and < 20
      IU/ml. Of the 45 patients who underwent second-look procedure, 27 had a positive
      outcome, while 18 were negative for residual disease. For CA 125 levels obtained
      after the third course of chemotherapy, a level > or = 35 IU/ml predicted a
      positive second-look outcome in three patients, but was not statistically
      significant (P = 0.143) when compared to patients with normal levels. Of patients
      with CA 125 > or = 35 IU/ml immediately prior to second-look procedure, nine had
      a positive outcome for second look, a difference that was statistically
      significant (P = 0.006) when compared to patients with normal levels. For the
      calculation of the slope of the regression curve, no statistical difference (P =
      0.838) was observed between the average of the slopes of the positive-outcome
      group and that the negative-outcome group. The only useful prediction of second
      look procedure outcome identified in this group of patients was an elevated (> or
      = 35 IU/ml) CA 125 immediately prior to second-look procedure. Elevated levels at
      this time predicted the presence of disease in 100% of patients. For the other
      methods of analyzing CA 125 levels during therapy, the outcome of second look
      could not be predicted in patients with no clinical evidence of disease.
      Selecting a lower normal level of 20 IU/ml did not increase our ability to
      predict second-look procedure outcome.

PMID- 7729731
TI  - Comparison between soluble tumor necrosis factor receptors and CA125 in
      peritoneal fluids as a marker for epithelial ovarian cancer.
AB  - The levels of the soluble forms of the membrane-bound receptor for tumor necrosis
      factor (TNF), p55 and p75, were assessed in peritoneal fluid samples from 50
      patients with ovarian cancer, from 20 patients operated for benign pelvic masses,
      and from 26 healthy women undergoing laparoscopy. The 95% cutoff for normal
      levels were 14.0 and 5.2 ng/ml for p55 and p75, respectively. In patients with
      active ovarian cancer, elevated levels of p55 and p75 were found in 54 (p55) and
      84% (p75) of the patients, and elevated levels were seen in all histologic types.
      The levels correlated with peritoneal fluid quantity and with stage of disease.
      Among 20 patients operated for benign pelvic masses, 1 patient had elevated p55
      and 8 patients (40%) had elevated p75. The concentration of CA125 in peritoneal
      fluids showed a 95% cutoff value in healthy individuals of 8.950 U/ml; and
      elevated CA125 levels were found in 7 patients with ovarian cancer (14%) and in
      none of the patients with benign masses. The results indicate that in peritoneal
      fluid, measurement of soluble TNF receptors, and particularly of p75, has an
      increased sensitivity and accuracy over CA125 in distinguishing ovarian cancer
      from benign pelvic masses.

PMID- 7729732
TI  - Loop electrosurgical excision procedure for intensified cytoreduction of ovarian
      cancer.
AB  - The objective was to evaluate the loop electrosurgical excision procedure (LEEP)
      for intensified cytoreduction of ovarian cancer. Twenty consecutive women with
      residual epithelial ovarian cancer following maximum cytoreduction by standard
      surgical techniques were treated with LEEP-intensified cytoreduction. LEEP was
      employed to resect metastases involving intestines (18 patients), diaphragm (3
      patients), liver (6 patients), spleen (3 patients), and peritoneal surface (18
      patients). Median LEEP time was 9 min (range 3-27 min). Blood loss secondary to
      LEEP was minimal with no patient experiencing bleeding > 20 ml. Following LEEP
      intensified cytoreduction, 17 of 20 patients (85%) had no gross residual disease.
      Seventeen of 18 patients (94%) had all intestinal metastases resected. All
      superficial liver (6 patients) and splenic metastases (3 patients) were
      completely resected. Peritoneal metastases were completely resected in all 18
      patients. No patient experienced a complication directly related to LEEP. LEEP
      can be performed rapidly, with minimum blood loss, and results in intensified
      cytoreduction with minimal morbidity.

PMID- 7729733
TI  - UCI-VULV-1, a vulvar squamous carcinoma cell line.
AB  - Squamous carcinoma of the vulva (SCV) is an uncommon neoplasm of uncertain
      etiology. There is evidence that there are two subgroups of SCV, one associated
      with human papilloma virus (HPV) and a second HPV-negative group. The UCI-VULV-1
      cell line, obtained from a lymph node metastasis of an SCV, grows with a
      population doubling time of approximately 60 hr. The saturation density is 10(5)
      cells/cm2. The cell line does not exhibit anchorage independence and is weakly
      tumorigenic. The cells range in appearance from an abundant spindle cell to a
      less common larger, flat cell. All of the cells are immunoreactive for high
      molecular-weight keratin, but only the flat cells, which form squamous pearls in
      vivo, are immunoreactive for low-molecular-weight keratin. The cell line
      expresses epidermal growth factor (EGF), transforming growth factor-alpha, the
      EGF receptor, and p53 protein. Polymerase chain reaction revealed no HPV DNA
      within the cells. Early passage cells exhibited karyotypic heterogeneity with few
      similarities to previous described SCV karyotypes. The cells display sensitivity
      to cis-platinum in concentrations toxic to many ovarian and cervical carcinoma
      lines. UCI-VULV-1 may be helpful for studying the properties of the HPV-negative
      form of SCV.

PMID- 7729734
TI  - Aberrations of the p53 tumor suppressor gene in human epithelial ovarian
      carcinoma.
AB  - Aberrations of the p53 gene in 26 surgical specimens of human epithelial ovarian
      carcinomas were examined by single-strand conformation polymorphism (SSCP)
      analysis of polymerase chain reaction (PCR) products. Seven (27%) of the tumors
      demonstrated a SSCP band shift in exons 4 to 9 of the gene, including 5 in the
      region encompassing exons 5 and 6, 1 in exon 7, and 1 in the region encompassing
      exons 8 and 9. Mutations were clustered in exon 5 in highly conserved regions of
      the p53 gene. All of the abnormal DNA fragments have been further characterized
      by direct DNA sequencing. These include five missense mutations (five
      transitions), a one-base-pair deletion introducing, by frameshift, a stop codon
      further downstream, and a two-base-pair insertion introducing a stop codon
      downstream by frameshift. Most mutations were base substitutions, and were
      clustered in exon 5 (71%), especially codons 175 and 179. The aberrations of the
      p53 gene were only found in tumors of FIGO stages III and IV. Histologic grading
      was also reviewed with respect to p53 aberrations. The aberrations were absent in
      well-differentiated carcinomas. The more undifferentiated the primary tumor, the
      more frequent p53 mutation (P < 0.05). Our results indicated that the aberrations
      of the p53 gene were common in epithelial ovarian cancers and p53 aberration may
      occur late during ovarian cancer evolution.

PMID- 7729735
TI  - Tumor antigens CA 19.9, CA 125, and CEA in carcinoma of the uterine cervix.
AB  - Serum levels of carcinoembryonic antigen (CEA) and cancer antigens CA 125 and CA
      19.9 were determined by immunoradiometric assay in 96 patients diagnosed of
      invasive carcinoma of the uterine cervix and 7 patients of cervical
      intraepithelial neoplasia. Elevated CEA levels were found in 33%, CA 19.9 in 32%,
      and CA 125 in 21.5% of invasive carcinoma patients. Specificity for each tumor
      marker was 98%. Increased CEA and CA 19.9 levels were found in relation to
      clinical stage. CA 125 and CA 19.9 mean levels were significantly higher in
      patients with adenocarcinoma compared with squamous cell carcinoma. Detection
      rate of CA 19.9 in stage III adenocarcinomas was higher than in stage III
      squamous cell carcinoma (50 vs 21%). Sensitivity of combined antigens was also
      higher for adenocarcinomas increasing 60% for CA 19.9 and/or CA 125 and to 70% of
      cases for one of the three tumor antigens. During follow-up of cases with no
      evidence of disease, antigen levels showed a tendency to decrease, but all cases
      with progressive disease, recurrence, or metastasis were detected by elevation of
      one of these three tumor antigens. In conclusion, CEA, CA 125, and CA 19.9 are
      useful markers for detection of cervical cancer and monitorization of clinical
      course of disease. CA 19.9 and CA 125 have been shown to be particularly useful
      in patients with adenocarcinoma.

PMID- 7729736
TI  - Mutant p53 in patients with invasive cervical cancer stages IB to IIB.
AB  - The present study evaluates the prognostic value of mutant p53 protein
      overexpression in 109 surgically treated cervical cancer stages IB to IIB.
      Squamous cell carcinoma stages IB, IIA, and IIB were present in 52, 13, and 44
      cases, respectively. We performed immunohistochemistry using a monoclonal
      antibody against the p53 suppressor gene product (clone BP53-12). Data were
      analyzed for the end points of disease-free survival and overall survival. In 109
      tissue specimens we detected 22 cases of p53 expression. Six of 22 patients with
      p53 expression and 21 of 87 patients without p53 expression showed tumor
      recurrences. p53 expression showed no significant correlation to age, tumor stage
      or lymph node involvement. In the univariate analysis p53 expression showed no
      prognostic value for disease-free (P = 0.5) and overall survival (P = 0.6).
      Multivariate analysis showed a significant prognostic value for established
      prognostic parameters while p53 expression had no prognostic value for recurrence
      free (P = 0.6) and overall survival (P = 0.5). In contrast to other malignancies
      mutant p53 overexpression showed no relation to prognosis in surgically treated
      cervical cancer stage IB to IIB.

PMID- 7729737
TI  - Surgical therapy of T1 and T2 vulvar carcinoma: further experience with radical
      wide excision and selective inguinal lymphadenectomy.
AB  - Radical wide excision and selective inguinal node dissection provide a more
      conservative and less morbid surgical option for women with vulvar carcinoma than
      en bloc radical vulvectomy with bilateral inguinofemoral lymphadenectomy. We have
      expanded our initial experience with this approach to 76 patients with T1 (n =
      33) and T2 (n = 43) squamous carcinomas with invasion > 1 mm and clinically
      negative groin nodes treated between 1978 and 1994. Lateral tumors (n = 53) were
      more frequent than midline lesions (n = 23). Tumors were excised with a measured
      gross margin of 2 cm, and dissection was carried to the deep perineal fascia. The
      mean largest tumor dimension was 26 mm; the mean depth of invasion was 4.4 mm.
      Superficial inguinal lymphadenectomy, unilateral or bilateral depending on lesion
      location, was performed. Perioperative complications occurred on the vulva in 8%
      of cases and in the groin in 11%. Delayed complications, all related to groin
      treatment, were seen in 29%. The median follow-up interval was 38 months. Seven
      patients (9%) had inguinal lymph node metastases identified at their primary
      operation. Most received additional therapy; one has died of disease. Nine women
      (12%) developed recurrent disease in the vulva: all were controlled by additional
      resection. Four (5%) developed recurrence in a previously negative groin: three
      of these are dead of disease. Actuarial 4-year survival is 81%. Radical wide
      excision and selective inguinal lymphadenectomy can be safely offered to women
      with T1 and T2 vulvar cancers. Patients with known positive nodes or vulvar
      failure can be salvaged by further therapy. Women with unanticipated groin
      failure usually die of disease. These experiences are similar to those observed
      in more radically resected patients.

PMID- 7729738
TI  - Perineal reconstruction using single gracilis myocutaneous flaps.
AB  - Bilateral gracilis myocutaneous flaps were originally used as part of a technique
      for creating a neovagina following total pelvic exenteration. Based upon this
      experience, we began using single flaps for primary repair and closure of large
      surgical defects in the perineal area that require alternate tissue sources to
      replace lost skin, mucosa, or adjacent deep tissues. Eighteen single gracilis
      flaps were used for major vulvovaginal reconstructions in 17 women during the
      past 5 years. Women undergoing unilateral flap reconstructions included 6 with
      anorectal cancers and 11 with vulvovaginal tumors. Most patients were being
      treated for recurrence after failed primary therapy (n = 7) or were receiving
      multimodal treatment for advanced local disease (n = 7). All cases involved
      complex resections followed by simultaneous reconstruction: mean total operative
      time was 377 min with a mean estimated blood loss of 1010 cc. Reconstruction
      involved external flap placement on the vulva or perineum in 7 cases and internal
      placement to replace excised portions of the vagina in the other 11. Mean flap
      size was 6.6 x 11.4 cm. Necrosis of flap skin occurred in 3 patients; minor wound
      separations or flap edge necrosis was seen in 5 cases. Hospital stay averaged
      18.4 days. Nine women had recurrent disease and died over 4-30 months; the
      remaining 8 are alive and disease free with a median follow-up of 25 months. The
      single gracilis flap provides a versatile method for providing anatomic
      reconstruction of large perineal defects in women who have undergone extensive
      resection.

PMID- 7729739
TI  - Immunologic diagnosis and monitoring of cervical cancers using in vitro
      translated HPV proteins.
AB  - E6 and E7 proteins, the transforming proteins of oncogenic HPVs, are known to be
      associated with the occurrence of cervical cancer. In radioimmunoprecipitation
      assays in which in vitro-transcripted and translated HPV-16 E6 and E7 proteins
      were used, patients with HPV-16-associated invasive cervical cancer (group I) had
      greater seroreactivity than patients in most of the other groups, including
      patients with invasive cervical cancer who were infected with other types of HPVs
      (group II), cervical cancer patients with nondetectable HPVs (group III),
      patients with HPV-16-associated cervical intraepithelial neoplasia (group IV),
      and unaffected normal controls with noncervical lesions (group V) (P < 0.05). The
      sera of patients in group I, when compared with the sera of other groups, were
      significantly reactive with one and/or two proteins (P < 0.05). Antibodies to HPV
      16 E6 and E7 proteins were detected in patients with invasive cancer more than in
      those with CIN. The positive rates for E6 protein were 4.2% (1/24), 43.8% (7/16),
      57.1% (8/14), 100% (5/5), and 100% (1/1), and the positive rates of E7 protein
      were 4.2% (1/24), 12.5% (2/16), 35.7% (5/14), 60% (3/5), and 100% (1/1) from CINs
      through stages I, IIa, IIb, and III of HPV-16-associated cervical cancers,
      respectively. The positive rates for E6 and E7 proteins were significantly
      increased with the advancing of the clinical stages of cervical cancer (P < 0.05
      for E6 and E7). To examine the change in antibody titers of HPV-16 E7 protein
      during diagnosis, treatment, and follow-up, we tested serial serum samples from
      14 patients of group I. The antibody titers were correlated to the clinical
      course of disease in some cases. The positive levels of E7 antibody were
      decreased when the treatment was effective, but in 1 patient who had shown
      recurrence or progression, positive seroreactivity was maintained. Antibodies to
      HPV-16 E6 and E7 proteins might be effective virus-specific and disease state
      specific markers of HPV-16-associated cervical cancer.

PMID- 7729740
TI  - Closed-suction drainage versus no drainage following radical abdominal
      hysterectomy with pelvic lymphadenectomy for stage IB cervical cancer.
AB  - Over a 7-year period from 1987 to 1994, 120 patients consecutive patients with
      FIGO stage IB invasive cervical cancer who underwent type 3 radical abdominal
      hysterectomy and bilateral pelvic lymphadenectomy had either Jackson-Pratt closed
      suction drainage (Group 1, patients 1-60) or no drainage (Group 2, patients 61
      120). All surgeries were performed by the author in a uniform manner. No increase
      in postoperative pelvic infection, fistula, or lymphocyst formation was noted in
      the group of patients with no drainage following radical hysterectomy and
      lymphadenectomy. Routine closed-suction drainage following radical hysterectomy
      and pelvic lymphadenectomy may be safely omitted.

PMID- 7729742
TI  - Tumor marker trends in asymptomatic women at risk for ovarian cancer: relevance
      for ovarian cancer screening.
AB  - The purpose of our study was to examine single and serial determinations of five
      biomarkers in asymptomatic women at risk for epithelial ovarian cancer to define
      median values and trends in a cancer-free cohort. Women were enrolled in the
      Gilda Radner Ovarian Cancer Detection program at Cedars-Sinai Medical Center, Los
      Angeles, California from July 1, 1991, to July 1, 1993. Biomarkers studied
      include CA-125, LASA, DM-70K, UGP, and HER-2. Biomarker values that were analyzed
      included those obtained on the first patient visit and in a subset of values
      evaluated at 6-month follow-ups. A total of 590 women were included in the study;
      425 were premenopausal and 165 were postmenopausal. No one in this study group
      has developed ovarian cancer within a 12-month follow-up period. Postmenopausal
      women had significantly lower values for CA-125 (12 vs 19 U/ml, P = 0.0001) and
      higher values of LASA (16.6 vs 15.4 mg/dl, P = 0.0001), DM/70K (11 vs 0 U/ml, P <
      0.001), UGP (3.3 vs 0.3 U/ml, P < 0.001), and HER-2 (12 vs 11 U/ml, P = 0.009)
      than premenopausal women. Less than 5% of the women had elevated tumor marker
      values on both screens except for CA-125, where 15% of women studied had two
      consecutive visits with elevated values (> 35 U/ml). Two women demonstrated an
      exponential rise in CA-125 between visits. Premenopausal women differ in median
      biomarker values compared to postmenopausal women. Elevations in single tumor
      markers, combinations of markers, and exponential increases of markers have all
      produced false-positive results for ovarian cancer within the 12-month follow-up
      period. Exponential increases produced the smallest false positive rate (n = 2),
      but further study and follow-up are needed to determine the efficacy of these
      tests in ovarian cancer screening.

PMID- 7729741
TI  - Phase II trial of methotrexate, vinblastine, doxorubicin, and cisplatin in
      advanced/recurrent carcinoma of the uterine cervix and vagina.
AB  - A phase II combination chemotherapy protocol combining methotrexate, vinblastine,
      doxorubicin, and cisplatin was designed to evaluate tumor response and survival
      in patients with advanced/recurrent cervix and vaginal cancer. Twenty-nine
      patients with advanced/recurrent cervix cancer and three patients with advanced
      vaginal cancer who had not previously received cytotoxic chemotherapy were
      assigned to chemotherapy treatment at 4-week intervals with methotrexate 30 mg/m2
      i.v., Day 1, vinblastine 3 mg/m2 i.v., Days 2, 15, and 22, doxorubicin 30 mg/m2
      i.v., Day 2, and cisplatin 70 mg/m2 i.v., Day 2. After a median of 4 cycles
      (maximum number 2 cycles beyond complete regression; 6 cycles with stable
      regression); we observed objective regressions in all 3 patients with vaginal
      cancer and 19 patients (66%, 95% CI = 46.82) with cervix cancer including
      complete regression in 6 patients (21%, 95% CI = 8.40) and partial regression in
      13 patients (45%, 95% CI = 26.64). Median overall survival was 11.5 months (range
      1.1-54+). Median survival of responders was 12.8 months (range 3.6-54+). Toxicity
      included neutropenia, alopecia, nausea, emesis, and stomatitis. Although grade 3
      and 4 neutropenia was observed in over half of the patients, there were no
      treatment-related deaths. In conclusion, MVAC is a highly active outpatient
      chemotherapy regimen in patients with advanced/recurrent cervix cancer, achieving
      a high complete and partial response rate with moderate hematologic toxicity.
      These results need to be confirmed by phase III trial in advanced disease
      patients and MVAC may be a suitable regimen for investigation in neoadjuvant
      chemotherapy trials in poor prognosis, previously untreated patients.

PMID- 7729743
TI  - Brain metastases in epithelial ovarian carcinoma.
AB  - Central nervous system metastases from epithelial ovarian carcinoma are uncommon.
      A retrospective study was undertaken to see if there was a difference in brain
      metastases from ovarian cancer in our patient population as compared to the
      literature. A retrospective study of all patients diagnosed with brain metastases
      from epithelial ovarian carcinoma at two institutions was performed. All patients
      were analyzed for stage, grade, type of chemotherapy, sites of recurrence, time
      to relapse, and survival after relapse. The results were compared to a
      compilation of reported cases from the literature. Sixteen patients with central
      nervous system metastases of 479 patients treated for ovarian carcinoma between
      January 1, 1979 and December 31, 1992 were identified. All 16 patients were
      diagnosed with serous cystadenocarcinoma, and all were either stage III or IV on
      presentation. Fifteen of the 16 patients had grade 2 or 3 disease. Histologic
      grade, at the time of diagnosis, did not influence survival after central nervous
      system recurrence; however, stage at original diagnosis did influence survival
      after brain metastases (P < 0.001). Eight of 11 patients undergoing second-look
      laparotomy had no evidence of disease. The most common presenting symptom of
      central nervous system disease was a slowly worsening headache of several weeks
      duration. The median time from original diagnosis to diagnosis of central nervous
      system disease was 19 months with a median survival after diagnosis of central
      nervous system disease of 3 months. The incidence of brain metastases in patients
      with epithelial ovarian carcinoma in our institutions was 3.3%. In conclusion,
      our incidence of brain metastases of 3.3% was not statistically significant from
      other reported rates. Patients who underwent radiation therapy with either
      craniotomy or chemotherapy for their brain metastases fared better than those who
      received radiation alone.

PMID- 7729744
TI  - Primary lymphatic dissemination of malignant elements in a mature cystic ovarian
      teratoma.
AB  - This case of malignant transformation in a mature cystic ovarian teratoma
      (dermoid cyst) is significant for the atypical manner in which the malignant
      elements metastasized to lymph nodes without evidence of intraperitoneal
      dissemination. The disease rapidly progressed and proved to be fatal in this
      premenopausal woman. The lesson learned is that lymph node inspection should be
      an integral component of the physical examination and exploratory laparotomy when
      this apparently benign ovarian neoplasm is encountered. Abnormal findings may be
      indicative of metastasis from an occult malignant transformation.

PMID- 7729745
TI  - Long-term remission of previously resistant choriocarcinoma with a combination of
      etoposide, ifosfamide, and cisplatin.
AB  - A 30-year-old white female was diagnosed with gestational trophoblastic disease
      in 1981. Despite an original World Health Organization score of 4 and initial
      aggressive combination chemotherapy, she was treated over a 9-year period with
      multiple chemotherapy agents and had undergone several operative procedures to
      remove metastatic lesions for persistent disease. Long-term remission has now
      been obtained after four courses of etoposide, ifosfamide, and cisplatin.

PMID- 7729746
TI  - Primary adenoid cystic carcinoma of Skene's glands.
AB  - A unique case of a 50-year-old woman is reported who presented with a suburethral
      mass in the anterior vaginal wall. The resected tumor was an adenoid cystic
      carcinoma arising from Skene's glands. Tumor was not involving Bartholin's
      glands. In addition to the typical glands and areas with cysts containing
      periodic acid-Schiff positive intraluminal material, less well-differentiated
      areas with neoplastic cells growing in a trabecular or solid pattern were also
      seen. Prominent perineural invasion was noted throughout the tumor.
      Immunostaining revealed positive reactions for cytokeratins, carcinoembryonic
      antigen, and focally for S-100 protein. Ultrastructural studies showed epithelial
      cells with well-formed basal lamina and prominent microvilli. This case
      illustrates an uncommon site, the Skene's glands for adenoid cystic carcinoma in
      the female genitourinary tract.

PMID- 7729747
TI  - Minimally invasive Paget's disease of the vulva with extensive lymph node
      metastases.
AB  - Optimal treatment for intraepithelial and invasive Paget's disease of the vulva
      has been previously evaluated. The treatment of disease with minimal invasion (<
      or = 1 mm) represents an even greater dilemma. We report a case of Paget's
      disease of the vulva with 1-mm depth of invasion presenting with extensive
      inguinofemoral lymph node metastases documented by fine-needle aspiration biopsy.

PMID- 7729748
TI  - Radiation recall reaction to idarubicin resulting in vaginal necrosis.
AB  - Radiation recall reactions are uncommon delayed tissue reactions seen in
      previously irradiated sites following treatment with cytotoxic agents. We
      evaluated a 64-year-old who developed two episodes of acute vulvitis and vaginal
      necrosis after receiving idarubicin therapy for acute myelogenous leukemia. Three
      years earlier she had undergone successful radiotherapeutic treatment of a stage
      I squamous cell carcinoma of the vagina. Her symptoms and examination findings
      resolved with local therapy and discontinuation of idarubicin. Recall reactions
      have been associated with the antitumor antibiotics actinomycin D and doxorubicin
      and, more recently, the mitotic inhibitors vinblastine and Taxol. The mechanism
      of this phenomenon is poorly understood but may be related to sequential stem
      cell injury or depletion. Because physical and biopsy findings are nonspecific,
      the diagnosis must be suspected on the basis of the patient's history and the
      location of the reaction within the prior treatment field.

PMID- 7729749
TI  - Intestinal perforation secondary to paclitaxel.
AB  - Three patients with colonic perforation following paclitaxel therapy are
      reported. This appears to be a direct drug effect causing mitotic arrest on the
      gastrointestinal epithelium. Eleven such patients with this complication have now
      been identified. While infrequent, this is a serious complication with a 57%
      mortality rate. The exact incidence of this complication is unknown and may have
      been previously underreported being attributed to progressive disease. A high
      index of suspicion of this complication should be considered for anyone
      presenting with abdominal pain following paclitaxel.

PMID- 7729750
TI  - [Comparison of donor defects of fibula and iliac crest grafts].
AB  - In order to study the donor-site morbidity following osteocutaneous fibula and
      iliac-crest flaps, 17 patients were asked to answer a questionnaire and to
      present for a follow-up examination. The donor defect after fibula graft was
      preferred to the iliac crest donor defect with respect to esthetic appearance and
      complication rate.

PMID- 7729751
TI  - [202 toe transfers to the hand].
AB  - This retrospective study analyzed 202 toe-to-hand transplants performed over the
      last 20 years at the Davies Medical Center, San Francisco (USA). The overall
      success rate was 97%. Toe transplants for finger reconstruction yielded optimal
      functional and cosmetic results due to their anatomical similarity to fingers.
      The great toe was preferably used for thumb reconstruction, whereas the other
      toes were used for reconstruction of the long fingers. Early reconstructions,
      multiple simultaneous toe transplants, and interventions combining toe
      transplantation with free flaps seemed to be advantageous because of shorter
      rehabilitation and comparable results.

PMID- 7729752
TI  - [Donor site morbidity of free flaps. A DAM (German Society for Microsurgery of
      Peripheral Nerves and Vessels) multicenter study--current status and literature
      review].
AB  - We present in this paper the multicentric study of donor-site morbidity in free
      flaps, conducted under the auspices of the Deutschsprachige Arbeitsgemeinschaft
      fur Mikrochirurgie der peripheren Nerven und Gefasse (DAM). To have a basis for
      evaluation of this and future research, we summarize previous results of
      literature.

PMID- 7729753
TI  - [Evaluation of long-term results and donor site defects following transposition
      of connective tissue flaps].
AB  - Nine patients suffering from chronic pain after surgery for thoracic outlet
      syndrome or after radiation therapy underwent neurolysis of the brachial plexus.
      To avoid a recurrence of scar formation, a pedicled subpectoral transposition
      flap of connective tissue, utilizing the pectoral branch of the A. thoraco
      acromialis, was wrapped around the neurolyzed structures. Long-term follow-up
      results are presented.

PMID- 7729754
TI  - [Donor site morbidity following radial forearm flap].
AB  - The results concerning morbidity of the fasciocutaneous radial forearm flap donor
      site of 20 patients are presented. The review was carried out with an average
      time of 4.4 years after raising the flaps, ranging from ten months to eleven
      years. Range of motion of the wrist joint was limited in extension in two
      patients with 15 degrees and in one patient with 30 degrees. Pinch and grip
      strength was found normal in 13 patients and was limited in five cases to 88% of
      the strength of the opposite limb. Dysesthetic areas were found in three patients
      on the radial border of the donor site and reduced sensation of the radial nerve
      was present in four patients.

PMID- 7729755
TI  - [Donor site morbidity in free rectus abdominis muscle flaps].
AB  - To evaluate donor-site morbidity, we used a questionnaire, which was answered by
      196 patients. 152 patients underwent a medical examination. The follow-up ranged
      from six month to ten years. The results of this retrospective study are
      presented. In 16,8%, we found hernia of the abdominal wall at the donor-site and
      relaxation was noticed in 32% of the cases. Painful symptoms of different degrees
      were reported by 50% of the patients.

PMID- 7729756
TI  - [Functional deficits following transfer of rectus abdominis muscle].
AB  - Functional deficits after raising of a rectus abdominis muscle flap in
      reconstructive surgery were evaluated retrospectively in 27 patients (11 female,
      16 male) and compared to 22 healthy control individuals. To test the torque of
      trunk flexion, the Cybex 6000 (TEF modular component) was used and subjects
      tested in a defined position allowing isolated sagittal flexion. For the rectus
      and oblique abdominal muscles, the Janda muscle function test was applied. For
      comparison of patients and controls, the Man and Whitney test was applied, and
      subgroup analyses were performed for men and women, respectively. The peak torque
      (relative to bodyweight) was significantly lower in patients as compared to
      controls, the differences being greater in men than in women, whereas clinical
      examination did not reveal a significant difference between either group. After
      autologous transplantation of the rectus abdominis muscle flap, compensation is
      obviously restricted to a certain degree, although the remaining deficit does not
      seem to represent a handicap in normal life. Thus the use of rectus abdominis
      muscle flaps in reconstructive surgery may be beneficial for the patient,
      provided the indication is precise and long-term control is possible.

PMID- 7729757
TI  - [Functional and esthetic assessment of donor site defects following transfer of
      the gracilis muscle].
AB  - In order to determine donor-site morbidity after elevation of the gracilis flap,
      53 patients from four different departments were examined. The patients filled
      out a questionnaire about their complaints. 36 patients underwent dynamometric
      measurements. The adduction strength of the hip-joint was decreased by 11% after
      elevation of the gracilis muscle. This decrease in strength was not noticed by
      the patients. 53% of the patients complained about hypesthesia or dysesthesia
      corresponding to the cutaneous territory of the obturator nerve. The contour of
      the thigh was adversely affected after elevation of a musculocutaneous flap. The
      gracilis flap has a low but definite donor-site morbidity, especially concerning
      the esthetic aspect.

PMID- 7729758
TI  - [Muscle-specific changes in free latissimus dorsi transplantation in the rat
      model].
AB  - The aim of this study is to gain further knowledge concerning the regeneration of
      reinnervated, freely transplanted muscles. Therefore, we used a rat model,
      consisting of eight rats per group, in which the latissimus dorsi muscle was
      transplanted orthotopically, after a period of time of two and twelve weeks
      harvested, then evaluated histologically and enzyme-histochemically. As controls
      we used a group of non-operated muscles. At date of removal, the patency of the
      vascular anastomoses was checked clinically and histologically. Additionally,
      electrophysiological measurements and conventional and enzyme-histochemical
      histologies were performed. Two weeks after the free neurovascular flap
      transplantation, the muscle was not innervated yet, histologically a dissolved
      pattern of type 1 and type 2 muscle fibers was found. After twelve weeks of time,
      the muscles were reinnervated again, muscle contraction was positive after
      electrical stimulation and the typical pattern of fibers was reestablished.

PMID- 7729759
TI  - [Which changes occur in nerve grafts harvested with a nerve stripper?
      Morphological studies].
AB  - A histological and morphometric study was undertaken in order to evaluate the
      alterations in sural nerves harvested for nerve grafting using a nerve stripper.
      In 19 nerves biopsies were taken from the proximal and/or the distal end of the
      stripped nerve graft. Cross sections were examined for alterations of the
      perineurium and the myelin sheaths. In four nerves alterations within the
      perineurium were found, which affected 37% of the endoneural cross-sectional area
      on the average. In all specimens, the perineurial sheath was seen to be intact.
      The results of the present study suggest that harvesting of a nerve graft using a
      stripper does not cause major injuries to the graft and therefore successful
      neurotization of the graft should not be impaired.

PMID- 7729760
TI  - Cloning of endoglucanase genes from Cellulomonas biazotea into E. coli and S.
      cerevisiae using shuttle vector YEp24.
AB  - We constructed a SmaI genomic library of Cellulomonas biazotea DNA in E. coli and
      in the S. cerevisiae shuttle vector, YEP 24. Three clone were identified that
      conferred the ability for E. coli or S. cerevisiae transformants to produce
      carboxymethylcellulase (CMCase). Cells transformed with these clones were
      compared with one another and with nontransformed cells for hyper-production of
      CMCase. In vivo and in vitro studies indicated that the CMCase genes were fully
      expressed and the enzyme activity was located extracellularly. The optimum pH and
      temperature for the CMCase thus cloned were pH 7 and 50 degrees C, respectively,
      as was the case for the donor.

PMID- 7729761
TI  - Direct selection shuttle plasmid vector, pPW264, used for cloning the alpha
      amylase gene of Schwanniomyces occidentalis.
AB  - We constructed a novel cloning system with positive selection for inserted
      fragments. The gene for tetracycline resistance (tetR) originally used in plasmid
      pTR262 was replaced with the gene for chloramphenicol acetyltransferase (cat) and
      terminator sequences were introduced downstream of the cat gene. The terminator
      sequences stop transcription originating on strong PR promoter that would
      otherwise proceed through the region of replication origin and interfere with
      plasmid replication. Thus the copy number of recombinant plasmid molecules is
      stabilized. The cloning system has been constructed in a new YEp type shuttle
      vector, pPW264. The 8.1 kb-vector carries two unique cloning sites, BglII and
      HindIII. The maintenance of the vector and selection in yeast is ensured by URA3
      Saccharomyces cerevisiae gene. The vector was employed in cloning of the gene for
      alpha-amylase from Schwanniomyces occidentalis.

PMID- 7729762
TI  - Enhancement of synthesis and activity of yeast transport proteins by metabolic
      substrates.
AB  - The transport rates of amino acids, ranging from L-Glu to L-Lys, uracil, adenine
      and sulfate and phosphate anions by Saccharomyces cerevisiae are greatly
      increased by preincubation with D-glucose in a nongrowth medium when a de novo
      synthesis of proteins takes place. In addition, some substrates, especially the
      inorganic anions, require the presence of glucose during their transport. This
      requirement has to do both with ongoing protein synthesis and degradation, as
      well as with providing energy and/or activating the plasma membrane H(+)-ATPase
      which supplies the protons to the H+ symports studied here.

PMID- 7729763
TI  - The influence of pH on growth kinetics of yeasts in the presence of benzoate as a
      sole carbon source.
AB  - The inhibitory effect and substrate properties of benzoic acid were estimated for
      25 yeast strains belonging to genera Candida, Hansenula, Hypopichia,
      Rhodosporidium, Rhodotorula, Saitoella and Trichosporon. Benzoic acid can serve
      as a sole carbon source for growth of yeasts belong to genera Rhodotorula,
      Rhodosporidium and Saitoella in synthetic mineral media. Specific growth rate is
      strongly dependent both on the concentration of benzoate and the pH value of the
      cultivation media. Maximum specific growth rate on benzoate is observed in
      alkaline cultivation media at pH 7.0-7.5 whereas those for growth on glucose in
      mildly acidic media at pH 5.0. Some of the strains showed weak growth on benzoate
      even at pH 8.5. Some carotenoid-containing yeasts of the genera Rhodotorula and
      Rhodosporidium lost their ability to synthesize carotenoid pigments during growth
      in alkaline benzoate media.

PMID- 7729764
TI  - Effect of chemical fertilizers on the transport of Escherichia coli, Pseudomonas
      aeruginosa and Salmonella infantis through sand columns.
AB  - Five commercial fertilizers, Amfos, ammonium sulfate, Kamex, Kieserit and NPK
      affected the transport of Escherichia coli, Pseudomonas aeruginosa and Salmonella
      infantis in sand columns. The percentage of cells transported through and without
      fertilizers during a 2-h period was species-dependent (0.56 for S. infantis, 3.1
      for E. coli and 12.4 for P. aeruginosa). The cell transport was enhanced by Kamex
      for all strains tested, whereas Amfos was found to decrease the transport of E.
      coli and S. infantis cells. A mathematical model revealed a relationship between
      the transport of cells and the pH of the sand columns with fertilizers. Columns
      in which the pH was decreased by the fertilizers exhibited a higher retention of
      cells. This points to the existence of physico-chemical surface interactions
      between cells and sand particles.

PMID- 7729765
TI  - Regulation of sterol biosynthesis in Saccharomyces cerevisiae.
AB  - Sterol synthesis in Saccharomyces cerevisiae was primarily controlled by the
      growth rate. At low specific growth rates the intermediates of ergosterol
      biosynthesis prevailed in cells. At the same time, the total sterol content
      reached about 6% of dry matter whereas the content of ergosterol was only 2-2.5%,
      which seems to be the maximum value for S. cerevisiae. After esterification with
      fatty acids these sterol intermediates are stored in lipid globules together with
      reserve triacylglycerols. The sporulating S. cerevisiae cells contained 3.5%
      sterols and 1.5% ergosterol of dry matter.

PMID- 7729766
TI  - Antimutagenic properties of fresh-water blue-green algae.
AB  - The antimutagenic properties of whole fresh-water blue-green algae Aphanisomenon
      flos-aquae, marketed under the commercial name "Alpha Sun" were tested using the
      Ames test. Simultaneous addition of both algae and Nitrovin (a mutagen) to the
      test medium did not reduce the mutagenic activity. On the other hand, addition of
      freeze-dried blue-green algae to the test medium 2-24 h before the application of
      mutagen reduced its mutagenic activity.

PMID- 7729767
TI  - Testing of the cytotoxic effects of sulfate pulp mill waste waters.
AB  - The effect of 22 technological waste water samples and of some standards was
      tested on bacteria, fungi, chlorococcal algae, flagellata, plant cells, cells of
      Tubifex tubifex, hamster cells V79 and the fish Lebistes reticulatus. Of these 22
      samples, some inhibition of cell life processes was displayed by the black liquor
      formed in the production of paper pulp and viscose pulp, by the waste solution
      produced during the preparation of bleaching agents for paper pulp and viscose
      pulp, and by the residual liquor after hypochlorite treatment of paper pulp.

PMID- 7729768
TI  - Effect of chlorinated phenol derivatives on various cell models.
AB  - Chlorinated phenol derivatives were found to display a cytotoxic effect on
      numerous cell models, such as chlorococcal algae, cyanobacteria, bacteria,
      micromycetes, plant and animal cells. Their cytotoxic effects will increase with
      chlorination and with the presence of a methoxy group.

PMID- 7729769
TI  - Application of the exploratory data analysis for evaluating the toxicity of
      chlorinated phenol derivatives by various cell models.
AB  - Exploratory data analysis based on multivariate statistical analysis techniques
      was introduced as a new approach to expressing the toxicity of chemical
      substances at the simultaneous acceptance of various cell models. Using principal
      component analysis and cluster analysis methods the toxicity of chlorinated
      phenol derivatives on employing some of the cell models (chlorococcal algae,
      cyanobacteria, bacteria, micromycetes, plant and animal cells) was characterized.
      The previous empirical experience that the toxicity of chlorinated phenol
      derivatives will increase with a growing degree of chlorination and that the
      presence of the methoxy group will cause a lowering of the toxic effect was
      demonstrated. The relationship between groups of tests used was presented.

PMID- 7729770
TI  - Virulence factors in clinical and food isolates of Aeromonas species.
AB  - Virulence factors were compared in 15 Aeromonas spp. isolated from faeces of
      patients with Aeromonas-associated gastroenteritis and in 81 strains isolated
      from food. Strains from food did not show differences in the distribution of
      virulence factors when compared with strains isolated from faeces. However, 88.8%
      of Aeromonas strains isolated from food were capable of producing possible
      virulence factors. Characterization of 28 autoagglutinating (AA+) Aeromonas spp.
      indicated that the human strains differed from the food strains in
      hemagglutinating and hemolytic capacities. These results suggest that
      autoagglutination associated with hemagglutinating and hemolytic capacities in
      food strains may be a helpful indicator of potential pathogenicity.

PMID- 7729771
TI  - Characteristics of Pseudomonas aeruginosa strains isolated from urinary tract
      infections.
AB  - Thirty-three uropathogenic strains of Pseudomonas aeruginosa were investigated
      for hemolytic activity in both bacterial broth culture filtrates and isolate
      lyzates, resistance to bactericidal activity of fresh human serum, resistance to
      six antibiotics and plasmid DNA profile. Twenty-four of the 33 (73%) bacterial
      filtrates showed lysis of rabbit erythrocytes, as did the three after guinea-pig
      erythrocyte treatment. Twelve of 33 isolate lysates showed in parallel lysis of
      both types of erythrocytes used. Serum resistance was found in 17 (52%) isolates,
      intermediate resistance in 15 (45 %) isolates and only one isolate showed serum
      sensitivity. Resistance to antibiotics was detected as follows (in %):
      tetracycline 94, kanamycin 79, chloramphenicol 76, septrin 73, ampicillin 64,
      streptomycin 45, gentamicin 18. None of the isolates investigated showed
      resistance to colistine. With the exception of one isolate, plasmid DNA was
      detected in all P. aeruginosa strains.

PMID- 7729772
TI  - Characterization of adhesion associated surface properties of uropathogenic
      Escherichia coli.
AB  - Escherichia coli was isolated from the urine of patients with pyelonephritis,
      with urinary tract infections other than pyelonephritis and with asymptomatic
      bacteriuria. Surface properties of the strains were analyzed by the salting-out
      aggregation test (SAT), hydrophobic interaction chromatography (HIC), Congo red
      binding (Crb), agglutination of erythrocytes (MRHA) and latex particles covered
      by digalactoside (PF) and by adherence to tissue culture cells. In addition, a
      DNA probe for the pap gene was used. The DNA probe detected the highest
      proportion of strains with pap gene in the group of patients with pyelonephritis,
      lower in the urinary tract infections other than pyelonephritis and the lowest in
      the group with asymptomatic bacteriuria. Tests for P-fimbriae (PF, MRHA) showed a
      similar distribution. Hydrophobicity measured by SAT and by HIC did not show
      differences among the tested groups of strains. The results suggest that factors
      other than the P-fimbriae and hydrophobicity may contribute to the persistence of
      E. coli in the urinary tract.

PMID- 7729773
TI  - A new phage typing scheme for Proteus mirabilis and Proteus vulgaris strains. 1.
      Morphological analysis.
AB  - A new bacteriophage typing set, composed of 22 phages, was established as a tool
      for differentiation of Proteus strains. All the phages were tailed and included 4
      morphological types (A1, A2, B1 and C1). They were classified into the families
      Myoviridae, Siphoviridae and Podoviridae. From the set, 19 phages had double
      stranded DNA and 3 were single-stranded DNA phages.

PMID- 7729774
TI  - Purification and characterization of alpha-amylase from Aspergillus flavus.
AB  - Aspergillus flavus produced approximately 50 U/mL of amylolytic activity when
      grown in liquid medium with raw low-grade tapioca starch as substrate.
      Electrophoretic analysis of the culture filtrate showed the presence of only one
      amylolytic enzyme, identified as an alpha-amylase as evidenced by (i) rapid loss
      of color in iodine-stained starch and (ii) production of a mixture of glucose,
      maltose, maltotriose and maltotetraose as starch digestion products. The enzyme
      was purified by ammonium sulfate precipitation and ion-exchange chromatography
      and was found to be homogeneous on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The purified enzyme had a molar mass of 52.5 +/- 2.5 kDa with an
      isoelectric point at pH 3.5. The enzyme was found to have maximum activity at pH
      6.0 and was stable in a pH range from 5.0 to 8.5. The optimum temperature for the
      enzyme was 55 degrees C and it was stable for 1 h up to 50 degrees C. The Km and
      V for gelatinized tapioca starch were 0.5 g/L and 108.67 mumol reducing sugars
      per mg protein per min, respectively.

PMID- 7729775
TI  - Accumulation of antifungal compounds in tea leaf tissue infected with Bipolaris
      carbonum.
AB  - Varietal resistance of tea towards Bipolaris carbonum was tested following
      detached leaf inoculation technique. Among the fourteen varieties tested, three
      were found to be highly susceptible, while other three were resistant. Leaf
      exudates and diffusates collected from the resistant varieties were more
      fungitoxic than those from the susceptible ones. Two antifungal compounds
      isolated from healthy and B. carbonum-infected tea leaves exhibited clear
      inhibition zones at RF 0.8 and 0.65, respectively, in a chromatographic bioassay.
      On the basis of their color reaction on TLC and UV-spectra these were identified
      to be catechin and pyrocatechol. Resistant and susceptible varieties accumulated
      439-510 and 187-212 micrograms/g fresh mass tissue of pyrocatechol, respectively,
      2 d after inoculation with B. carbonum, while a low concentration (45-58
      micrograms/g) of this compound was detected in healthy leaf tissue.

PMID- 7729776
TI  - Antibacterial activity of human mononuclear leukocytes against Staphylococcus
      aureus.
AB  - Human mononuclear leukocytes kill Staphylococcus aureus cells in vitro. The
      killing of the bacteria takes place even in the absence of antibodies. The
      presence of antibodies (in an autologous inactivated serum) usually enhances the
      antibacterial activity of mononuclear leukocytes. In some cases, however, this
      activity is markedly decreased by the serum, probably depending of the spectrum
      of antibodies contained in the serum. The antibacterial activity of mononuclear
      leukocytes is mostly due to monocytes because their depletion causes substantial
      drop or the activity disappearance. We failed to demonstrate in the case of S.
      aureus the antibacterial cytotoxicity of T lymphocytes described by some authors
      dealing with Gram-negative bacteria. Large differences in the structure of the
      bacterial cell wall underlie apparently the different sensitivity of G+ and G-
      bacteria to some protective mechanisms of the host. In the antibacterial assay
      against S. aureus, electron microscopy revealed a maximal activation of monocytes
      which phagocytized the bacteria although extracellular killing is not excluded.
      Electronoptical findings point also to a possible participation of NK cells in
      the antibacterial cytotoxicity against S. aureus.

PMID- 7729777
TI  - The polybacterial lysate Olimunostim modulates lymphocyte function in vitro and
      restores depressed cellular immunity in vivo.
AB  - Immunobiological activity of the polybacterial lysate Olimunostim (P. acnes, K.
      pneumoniae, S. aureus) was examined by investigating its effects on murine
      lymphocytes. When added to in vitro lymphocyte cultures, Olimunostim induced
      interleukin-2 (IL-2) biological activity (in a 2-d culture) and subsequently
      potentiated lymphocyte proliferation (on day 3); the latter effect was dependent
      on the presence of adherent cells. In vivo, significant enhancement of lymphocyte
      reactivity to T-mitogens and increase of CD4+ helper-inducer T lymphocytes were
      observed 3 d after a subcutaneous application of Olimunostim to mice with
      cellular immune deficiency. These results confirm the modulatory properties of
      Olimunostim towards lymphocytes both in vitro and in vivo, which may form a basis
      for its clinical application.

PMID- 7729778
TI  - Structural correlates of antifungal and cytotoxic activity of brefeldin A: the
      importance of a rigid planar lactone ring.
AB  - Molecular modelling of brefeldin A and its derivatives shows that the presence of
      a rigid and planar lactone ring conformation is necessary for cytotoxic and anti
      fungal activity. Cytotoxic compounds had lactone ring torsion angles of -28.77 +/
      6.13 degrees, while non-cytotoxic compounds had torsion angles of -88.25 +/-
      14.6 degrees.

PMID- 7729779
TI  - [Molecular biological pathophysiology of chronic myelogenous leukemia].

PMID- 7729780
TI  - Three-dimensional analysis of the intrinsic cardiac ganglia in a young dog.
AB  - The intrinsic ganglia of the heart of a young dog were studied by computer
      graphic reconstruction to determine the accurate location. The heart was embedded
      in celloidin, and transverse sections were cut. Using every third 60 microns
      section, a series of 49 sections was mapped. Three-dimensional (3D) images were
      constructed by a personal computer. Numerous intrinsic ganglia, most of which
      were located in the epicardiun, were observed. The intrinsic ganglia were found
      in the base of the aorta and pulmonary vessels and from the base of the superior
      vena cava to the right atrium, i.e., the sinoatrial nodal region. Using the 3D
      reconstruction technique, the locations of the intrinsic ganglia could be
      accurately identified. Furthermore, it was demonstrated that these ganglia formed
      several groups which formed a continuity. This study suggested that it was
      necessary to consider the existence of the numerous intrinsic ganglia, when we
      studied the cardiac innervation.

PMID- 7729781
TI  - [Prophylactic effect of methylprednisolone on cisplatin-induced nephrotoxicity].
AB  - Cis-diamminedichloroplatinum (II) (cisplatin) is an effective antitumor drug, but
      it has an adverse effect of nephrotoxicity. There are many reports concerning
      protective agents against cisplatin nephrotoxicity. However, clinically useful
      modalities are very few because the mechanism of action was not well evaluated.
      In the present study, prophylactic effects of methylprednisolone (MP) on
      cisplatin-induced nephrotoxicity and its mechanism were studied. Male Sprague
      Dawley rats were intravenously injected with 6.5 mg/kg of cisplatin combined with
      a subcutaneous MP in various doses at various timing. Rats were killed 5 days
      after cisplatin injection to determine BUN and serum creatinine. BUN and serum
      creatinine levels in rats pretreated with MP 4 or 2 hours prior to cisplatin
      injection were significantly lower than those in rats received cisplatin alone.
      To evaluate the mechanism responsible for the protective action of MP against
      cisplatin-induced nephrotoxicity, the effects of MP on platinum kinetics and the
      excretion of urinary enzymes following intravenous administration of cisplatin in
      vivo were studied. Rats intravenously injected with cisplatin combined with a
      subcutaneous MP injection excreted more platinum in their urine than rats which
      had received cisplatin alone. Plasma and kidney platinum concentrations in rats
      injected with both cisplatin and MP were significantly lower than those in rats
      given cisplatin alone, at 4 hours after the cisplatin injection. These findings
      indicate that the MP-induced increase in urinary platinum excretion accompanied
      by a decrease in plasma and kidney platinum concentrations following cisplatin
      injections in rats is one of the possible mechanisms responsible for the
      protective action of MP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729782
TI  - [The usefulness of portable 24-hour polygraphic monitoring--evaluation of
      autonomic nervous activity of the patients with ischemic heart disease by using
      heart rate variability during sleep].
AB  - Portable 24-hour polygraphic monitorings were performed on 109 cases with
      neurological or cardiovascular disorders, sleep disturbances and metabolic
      diseases to clarify its usefulness and limitations. Moreover, an evaluation of
      autonomic nervous activity was done in different stages of sleep in normal young
      (n = 9), normal middle-aged subjects (n = 8) and patients with ischemic heart
      disease (n = 7) using power spectral analysis of heart rate. The parameters
      recorded in this study were electroencepharogram(EEG), electrooculogram,
      electromyogram of chin muscles, electrocardiogram, respiratory curve, walking
      pulse and body position. Using polygraphic monitoring, the patients with cardiac
      arrhythmia showed abnormal EEG in 20% and those with neurological events in
      86.7%. The improvement of sleep structure was found after pacemaker implantation
      in the patients with bradyarrhythmias (75%). Time spans of slow wave sleep and
      REM sleep of patients with ischemic heart disease decreased significantly from
      120.9 +/- 40.6 min to 79.1 +/- 25.3 min, 112.8 +/- 16.5 min to 63.6 +/- 23.6 min,
      respectively (p < 0.05). RR50, that is number of R -R intervals greater than
      50msec compared to the preceding R-R interval, decreased significantly in each
      stage of sleep in the patients with ischemic heart disease compared to normal
      subjects (stage 2: 18.3 +/- 6.1/min to 3.8 +/- 3.0/min, p < 0.01; SWS: 7.8 +/-
      8.0/min to 3.2 +/- 2.5/min, p < 0.05; REM: 17.9 +/- 6.0/min to 4.4 +/- 4.3/min, p
      < 0.01). The HF power in all stages of sleep showed a trend of the decrease in
      the patients with ischemic heart disease. In REM sleep, the LF power in patients
      with ischemic disease was lower significantly compared to that in normal middle
      aged subjects (6.1 +/- 3.2 to 12.1 +/- 4.1, p < 0.05). The L/H ratio also
      decreased significantly (1.08 +/- 0.30 vs. 2.35 +/- 1.03, p < 0.05). The slope of
      1/fx above 0.15Hz in IHD patients was less in stage 2 (-0.404 +/- 0.280 vs. 
      0.849 +/- 0.183, p < 0.01) and in REM sleep (-0.294 +/- 0.368 vs. -0.665 +/-
      0.291, p < 0.05). Above results suggest the involvement of a decrease of
      sympathetic activity in addition to decrease of parasympathetic activity
      especially in REM sleep in the patients with ischemic heart disease. In
      conclusion, polygraphic monitoring is useful for a detection of abnormality of
      EEG and an evaluation of autonomic activity in cardiovascular disorders.

PMID- 7729783
TI  - The progressive degeneration of interlobular bile ducts in biliary atresia: an
      ultrastructural study.
AB  - The ultrastructure of the interlobular bile ducts were observed in hepatic
      specimens obtained at surgery in ten patients with biliary atresia, in order to
      investigate the progress of their degeneration over time after the onset of the
      disease. As an index for the passage of time, the degree of fibrosis in the
      portal tracts was investigated. Then the ultrastructural features in the
      interlobular bile ducts were contrasted with the grading of portal fibrosis
      Generally, the ultrastructural changes of the interlobular bile ducts were more
      marked in the cases with severe portal fibrosis than that observed in the cases
      with mild fibrosis. This correlation suggests that the degeneration of the
      interlobular bile ducts progressively worsens over time after the obliteration of
      the extrahepatic bile duct.

PMID- 7729784
TI  - Mathematical descriptions of the glucose control in diabetes therapy. Analysis of
      the Schlichtkrull "M"-value.
AB  - Mathematical indices describing metabolic control of the diabetic patients during
      a short-term (24 hours) monitoring period have been reviewed. Two groups of
      indices were selected: those related to the glucose level and those related to
      the glycaemia variations. Then a presentation of the most universal mathematical
      index, which is presently used in clinical practice, -M value - was performed.
      Due to certain discrepancies related to several versions of the M-index, an
      analysis of all variants (M80, M90, M100, M120) had been carried out. It was
      found that comparison of the M values calculated based on different glucose
      reference levels led to totally different results. Analysis indicated that for
      the considered profiles the best description of the glycaemic state can be
      obtained when levels of 80 mg/dl (M80) and 90 mg/dl (M90) are applied.

PMID- 7729785
TI  - Time-course of hypothalamic CRH and pituitary ACTH contents, and pituitary
      responsiveness to CRH stimulation after bilateral adrenalectomy.
AB  - The pituitary ACTH and hypothalamic CRH alterations at different periods after
      adrenalectomy (ADX) or Sham ADX were studied by measurement of ACTH and CRH
      contents by radioimmunoassay (RIA) in rats. We also studied the corticotroph
      alterations by immunohistochemistry and the in vitro pituitary responsiveness to
      CRH. Plasma ACTH presented a triphasic response after ADX. Anterior pituitary
      (AP) ACTH content decreased 3 h and 1 day after surgery, then rose over this
      period. Immunohistochemistry demonstrated an initial degranulation of the
      corticotrophs with a progressive increase in cells immunostained for ACTH and a
      positive correlation (r = 0.88) with AP ACTH content measured by RIA.
      Hypothalamic CRH content decreased after ADX, but returned to sham value 3 weeks
      later. Basal ACTH secretion in incubation medium was correlated with the AP ACTH
      content observed in vivo. The pituitary responsiveness to CRH was not the same at
      all times after ADX. It was absent 1 day after, presented an increase of 51%,
      117% and 26% when compared with the basal ACTH output 3 h, 3 and 14 days after
      ADX, respectively. Our data suggest that after ADX the corticotroph undergoes a
      transitory decrease in ability to secrete ACTH after store depletion. During a
      later phase, however, there is a relative hyporesponsiveness of the corticotroph
      to CRH stimulation. These data indicate that CRH may be acting on a down
      regulated pituitary or more additional factors play a role in the sensitization
      of the pituitary after ADX.

PMID- 7729786
TI  - Endothelium is a target organ of parathyroid secretions in genetic hypertensive
      rats.
AB  - We investigated the relationships between vascular endothelium and parathyroid
      function. Blood pressure (BP), circulating endothelins (ETs) and atrial
      natriuretic peptide (ANP), and BP responses to parathyroid hormone (PTH) and NG
      nitro-L-arginine methyl ester (L-NAME) were measured in parathyroidectomized
      (PTx), PTx and fed a Ca2+ enriched diet (PTx-HCa) and sham SHR.22 weeks after
      surgery, BP was significantly decreased in PTx and PTx-HCa, plasma ETs levels
      were increased, whereas ANP levels were decreased. In anesthetized rats, BP
      increase induced by L-NAME was greater in PTx-HCa than in sham group, indicating
      increased endogenous nitric oxide release in hypoparathyroid rats. The
      hypotensive response to PTH remained unchanged. These data demonstrate that
      endothelium is activated in long-term hypoparathyroid SHR, reflecting an
      adaptative response to decreased BP.

PMID- 7729787
TI  - Liver glucokinase: decreased activity in patients with type II diabetes.
AB  - Because of the demonstration of a genetic linkage between glucokinase and Type II
      diabetes, and the central role of glucokinase on glucose metabolism, we studied
      glucokinase activity in the liver of patients with and without Type II diabetes.
      Glucokinase activity was decreased by about 50% in obese subjects with diabetes
      (n = 12) compared with (p < 0.01) lean controls (n = 9) and (p < 0.05) obese
      controls (n = 10). There was no difference between lean and obese controls. Fifty
      percent of subjects with diabetes had lower liver glucokinase activity than the
      lowest value of the controls. These data further support the important role that
      glucokinase plays in the pathogenesis of Type II diabetes.

PMID- 7729788
TI  - Diurnal variation of growth hormone responses to acutely administered
      dexamethasone in healthy male volunteers.
AB  - Acute administration of exogenous corticosteroids stimulates growth hormone (GH)
      release. Physiological fluctuations of plasma cortisol appear to have an effect
      on the circadian release of GH. The purpose of this study was to examine the
      effects of the diurnal variation of plasma cortisol on dexamethasone (DEX)
      induced GH responses in healthy volunteers. Six healthy male subjects were
      studied using a randomised cross-over design. Subjects were tested twice, with an
      interval of two weeks between tests, at 9.00 h and 14.00 h. After baseline levels
      for GH and cortisol were taken, subjects received 4 mg of oral DEX and blood
      samples were drawn at + 60, + 180, + 240 and + 300 minutes later. GH levels
      peaked 3 hours post-DEX administration and were greater in the morning than in
      the afternoon. Mean +/- SEM delta GH values at 9.00 h and 14.00 h were 14.1 +/-
      2.7 ng/ml and 6.9 +/- 1.6 ng/ml, respectively (t = 2.36, df = 1.10, p < 0.04).
      DEX-induced GH release appears to undergo a diurnal variation.

PMID- 7729789
TI  - Blunted GH response to growth hormone-releasing hormone (GHRH) alone or combined
      with arginine in non-insulin-dependent diabetes mellitus.
AB  - An increased spontaneous and stimulated growth hormone (GH) secretion is well
      documented in insulin-dependent diabetes mellitus. On the contrary, in non
      insulin-dependent diabetes mellitus (NIDDM) conflicting results arise from
      literature. In 14 patients with NIDDM, 7 normal weight (NWD) and 7 obese (OD), we
      investigated the somatotrope responsiveness to GHRH (1 microgram/kg) alone or
      combined with arginine (ARG, 0.5 g/kg), which is able to enhance the GH response
      to GHRH, probably by inhibiting somatostatin release from hypothalamus. Baseline
      IGF-I, IRI FFA and glucose levels were also determined. Twelve healthy normal
      subjects (NS) and 12 obese patients (OP) were evaluated as control groups. GH but
      not IGF-I levels were higher (p < 0.05) in NS than in OP (1.5 +/- 0.5 vs 0.5 +/-
      0.2 microgram/l). Insulin levels were higher (p < 0.05) in OP than in NS, NWD and
      OD (18.7 +/- 1.8 vs 8.7 +/- 0.5, 6.4 +/- 1.9 and 11.8 +/- 1.2 microU/l). FFA were
      higher (p < 0.05) in NWD. OD and OP than in NS (0.69 +/- 0.04, 0.70 +/- 0.04 and
      0.65 +/- 0.06 vs 0.39 +/- 0.03 mmol/l). Plasma glucose was higher (p < 0.05) in
      diabetic patients than in normal and obese subjects. GH responses to GHRH in NWD,
      OD and OP were similar (AUC: 221.6 +/- 33.3, 206.0 +/- 35.9 and 177.2 +/- 57.3
      micrograms/l/min, respectively) and all lower (p < 0.05) than that in NS (776.7
      +/- 206.5 micrograms/l/min). ARG determined a significant increase of GHRH
      induced GH release in all groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729790
TI  - Effect of antibodies to calcitonin on the pharmacokinetics and the
      pharmacodynamics of the hormone.
AB  - Calcitonin pharmacokinetics and pharmacodynamics were studied in two groups of
      patients with postmenopausal osteoporosis, who, treated for one year with
      intranasal Asu1.7-eel calcitonin (eCT), had (Ab+) and had not (Ab-) developed a
      specific immune response to the drug. The treatment consisted of daily intranasal
      administrations of eCT (80 IU/die) with 1 g supplemental calcium. Eight women who
      had developed specific antibodies and 5 who had not, were given 50 IU of CT i.m.,
      in order to assess the pharmacokinetics and pharmacodynamics of the drug. The
      rise of serum levels of the hormone was significantly greater in Ab+ than in Ab-
      patients. At the end of the study, no significant differences in mineral bone
      loss between the two groups were found. In conclusion, the presence of antibodies
      to eCT does not represent a negative event in the therapy of osteoporosis, but
      significantly affects the pharmacokinetics of the drug.

PMID- 7729791
TI  - Interleukin-6 stimulates insulin secretion in HIT-T 15 cells.

PMID- 7729792
TI  - In vitro regulation of calbindinD28K mRNA by 1,25-dihydroxyvitamin D3 and
      estradiol in precociously-matured egg shell gland from vitamin D3-depleted
      chicks.

PMID- 7729793
TI  - "J"-index. A new proposition of the assessment of current glucose control in
      diabetic patients.

PMID- 7729794
TI  - Effect of methylcobalamin on diabetic autonomic neuropathy as assessed by power
      spectral analysis of heart rate variations.

PMID- 7729795
TI  - Subacute thyroiditis associated with interferon-alpha 2a therapy.

PMID- 7729796
TI  - 14th Workshop of the study group Artificial Insulin Delivery Systems, Pancreas
      and Islet Transplantation (AIDSPIT) of the European Association for the Study of
      Diabetes (EASD). Igls, Austria, 30-31 January 1995. Abstracts.

PMID- 7729797
TI  - Effect of insulin on renal vascular escape in normal and diabetic kidney.
AB  - Renal Vascular Escape was studied in the isolated perfused kidney harvested from
      diabetic and normal rabbits. Diabetes was induced 3-4 weeks earlier by injecting
      the animals with 150 mg/kg alloxan IP. To induce vasoconstriction, norepinephrine
      (10(-6) M) (NOR) was infused to the renal artery for 20 min, during 3 cycles,
      with intervals of 10 min for drug wash out, with a total duration of 90 min of
      observation. Administration of NOR induced intense vasoconstriction which was
      followed by a period of relaxation, in spite of the continued infusion of the
      adrenergic neurohormone. This was named renal vascular escape (RVE). RVE was
      present in all control animals but was severely impaired in diabetic kidneys. The
      administration of insulin (20 mU/ml or 2 mU/ml) to the perfusate promoted a
      significant blockade of escape (p < 0.001) in normal kidneys, which was time
      dependent, and only a slight effect in the diabetic group. These data show an
      interaction between insulin and RVE in normal animals and could point out another
      defect in diabetes, as related to insulin resistance.

PMID- 7729798
TI  - Special issue: U.S.--Japan Symposium on Brain and Steroids. April 1994.

PMID- 7729799
TI  - Role of sex steroids on the survival, neuritic outgrowth of neurons, and dopamine
      neurons in cultured preoptic area and hypothalamus.
AB  - Morphological sex differences in some discrete brain regions are thought to be
      developed by the influence of circulating androgen during the perinatal period.
      In order to know whether the effect of androgen is a direct one, cells derived
      from neonatal rat preoptic area (POA) and/or hypothalamus were cultured in a
      serum-free medium, and the effects on survival, process growth of neurons, and
      dopaminergic function were examined. When the POA cells were exposed to
      testosterone (T), neuronal survival was greater than the controls, and the
      frequency distribution of total process length and the number of process
      branchings were significantly deviated from the controls. Estradiol-17 beta (E2)
      and 5 alpha-dihydrotestosterone had less significant effects on these parameters
      than T. Moreover, the addition of T increased the dopamine (DA) contents of cells
      and medium DA in the hypothalamic culture. E2 also greatly increased DA content
      of the medium. These steroids failed to alter the DA levels in the POA cell
      cultures. These results generally conform to the notion of previous investigators
      that T has direct effects on the expansion of dendritic elements of the POA and
      the development of sex difference in the hypothalamic DA neurons, although the
      effect of T after conversion to E2 cannot be excluded.

PMID- 7729800
TI  - Androgen enhances neuronal degeneration in the developing preoptic area:
      apoptosis in the anteroventral periventricular nucleus (AVPvN-POA).
AB  - Perinatal treatment of female rats with androgen decreases the nuclear volume of
      the anteroventral periventricular nucleus of the preoptic area (AVPvN-POA). In
      order to examine the effect of androgen on neurogenesis, bromodeoxyuridine (BrdU)
      was given once on Day 15 of gestation (= E15) to pregnant rats that also received
      testosterone propionate (TP) injections. When examined at E17, the number of BrdU
      labeled neurons in the AVPvN-POA was not significantly different among control
      female, male, and androgenized female fetuses, suggesting that androgen does not
      interfere with neurogenesis. At E21, a significant reduction of BrdU-labeled
      AVPvN neurons was observed in males and androgenized females. These findings
      support the hypothesis that elimination of a population by cell death is enhanced
      in males and androgenized females. Similar selective elimination of the AVPvN
      neurons occurred in the female following neonatal TP treatment. In order to
      investigate the nature of androgen-induced cell death in the AVPvN-POA, specific
      labeling of nuclear DNA fragmentation was performed by the TdT-mediated dUTP
      biotin nick end-labeling (TUNEL) method. The number of TUNEL-positive cells was
      significantly greater in neonatally androgenized females, compared to that in
      control females. Since DNA fragmentation is considered the most characteristic
      feature of apoptosis, and TUNEL method is based on direct, specific labeling of
      DNA fragmentation in nuclei in situ, the neuronal death in the AVPvN-POA is
      apoptotic, and perinatal androgen may induce the selective apoptotic cell death
      in the AVPvN-POA.

PMID- 7729801
TI  - Can gonadal steroids influence cell position in the developing brain?
AB  - The preoptic area/anterior hypothalamus (POA/AH) is a site where hormones
      dramatically influence development. The POA/AH is comprised of multiple
      subgroups, but little is known about the derivation of these subgroups during
      development. Results from several laboratories suggest that some cells in the
      POA/AH originate from progenitor cells in other regions of the developing nervous
      system. We are exploring pathways for migration in the developing POA/AH in two
      ways. First, we are examining the distribution of radial glial processes as
      potential migratory guides using immunocytochemistry. We have identified a
      transient pattern of radial glial processes from the lateral ventricles to the
      pial surface at the base of the POA/AH. Additionally, the expression of a
      molecule in radial glial processes originating in the third ventricle was
      decreased by prenatal treatment with testosterone. Second, we are utilizing time
      lapse video microscopy in vitro to assess the extent and direction of movements
      of fluorescent dye-labeled cells at different ages in brain slice preparations
      from the POA/AH of developing rats. Data from these studies indicate that cell
      migration in the POA/AH includes movements along dorsal-ventral routes and from
      lateral to medial positions, in addition to the predicted medial to lateral
      pathway away from the third ventricle. Several researchers have examined effects
      of gonadal steroids on neurite outgrowth, cell differentiation, cell death, and
      synaptogenesis. The determination of cell position, however, may be a key event
      influenced by gonadal steroids earlier in development. The characterization of
      migratory pathways that contribute to permanent changes in brain structure and
      ultimately function is essential for unraveling the process of sexual
      differentiation.

PMID- 7729802
TI  - Neurotoxicity of glucocorticoids in the primate brain.
AB  - Severe and prolonged physical and psychological stress is known to cause brain
      damage; long-term torture victims in prison have later developed psychiatric
      disorders and cerebral cortical atrophy observed in CT scans (Jensen, Genefke,
      Hyldebrandt, Pedersen, Petersen, and Weile, 1982). In nonhuman primates, we
      observed degeneration and depletion of the hippocampal neurons in African green
      monkeys that had been severely abused by cagemates and died with complications of
      multiple gastric ulcers and adrenal cortical hyperplasia (Uno, Tarara, Else,
      Suleman and Sapolsky, 1989). In our previous studies the administration of
      dexamethasone (DEX) (5 mg/kg) to pregnant rhesus monkeys at 132 to 133 days of
      gestation induced degeneration and depletion of the hippocampal pyramidal and
      dentate granular neurons in the brains of 135-gestation-day fetuses, and these
      changes were retained in the brains of fetuses at near term, 165 days of
      gestation (Uno, Lohmiller, Thieme, Kemnitz, Engle, Roecker, and Farrell, 1990).
      We also found that implantation of a cortisol pellet in the vicinity of the
      hippocampus in adult vervet monkeys induced degeneration of the CA3 pyramidal
      neurons and their dendritic branches (Sapolsky, Uno, Rebert, and Finch, 1990).
      Thus, hippocampal pyramidal neurons containing a high concentration of
      glucocorticoid receptors appear to be highly vulnerable to either
      hypercortisolemia caused by severe stress or to exposure to exogenous
      glucocorticoids. To study the long-term postnatal sequelae of prenatal brain
      damage, eight rhesus monkeys were treated with either DEX (5 mg/kg), 5 animals,
      or vehicle, 3 animals, at 132 to 133 days of gestation. After natural birth, all
      animals lived with their mothers for 1 year. At 9 months of age, we found that
      DEX-treated animals had significantly high plasma cortisol at both base and post
      stress (isolation) levels compared to age-matched vehicle-treated animals.
      Magnetic resonance images (MRI) of the brain at 20 months of age showed an
      approximately 30% reduction in size and segmental volumes of the hippocampus in
      DEX-treated compared to vehicle-treated animals. Measurements of whole brain
      volume by MRI showed no significant differences between DEX and vehicle groups.
      Prenatal administration of a potent glucocorticoid (DEX) induced an irreversible
      deficiency of the hippocampal neurons and high plasma cortisol at the circadian
      baseline and post-stress levels in juvenile rhesus monkeys. These results suggest
      that the hippocampus mediates negative feedback of cortisol release; a lack or
      deficiency of the hippocampal neurons attenuates this feedback resulting in
      hypercortisolemia.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7729803
TI  - Dynamic changes in LHRH neurovascular terminals with various endocrine conditions
      in adults.
AB  - Luteinizing hormone-releasing hormone (LHRH) release is required for ovulation in
      mammals. Although evidence for the direct action of gonadal steroids on LHRH
      neurons has been minimal, their importance in inducing the preovulatory surge of
      LHRH is unequivocal. We have identified a subgroup of LHRH neurons with progestin
      receptors in guinea pigs. Given their central position, these neurons may
      constitute foci of initial activity, which are amplified throughout the
      population of LHRH neurons, resulting in increased LHRH neurosecretion on the
      afternoon of proestrus. Additionally, gonadal steroids may regulate LHRH
      secretion at the level of the terminals. Using immunoelectron microscopy and
      image analysis, we have illustrated the dramatic influence of gonadal steroids on
      individual LHRH terminals in the median eminence of rats. Indirectly, gonadal
      steroids may modulate LHRH release by modulating glial elements. Using double
      label fluorescence confocal microscopy, we illustrate that LHRH terminals in the
      median eminence are encased by end-feet of tanycytes. Acting on glial elements,
      gonadal steroids may regulate access of LHRH terminals to the basal lamina and
      influence the amount of the neuropeptide reaching the portal vessels. We propose
      that during the preovulatory surge, LHRH release is coordinated by synergistic
      mechanisms operating at the level of particular subgroups of neuronal perikarya
      and/or discrete regions of the median eminence. These synergistic actions may
      ensure that LHRH is released in a precipitous fashion, to induce the surge of LH
      from the pituitary, required for ovulation.

PMID- 7729804
TI  - Androgen regulates gene expression of cytoskeletal proteins in adult rat
      motoneurons.
AB  - Expression of beta-actin and beta-tubulin mRNA was examined in androgen-sensitive
      motoneurons of the spinal nucleus of the bulbocavernosus (SNB) in adult male rats
      by in situ hybridization histochemistry using complementary DNAs encoding chick
      beta-actin and mouse beta-tubulin, respectively. Both hybridizable beta-actin and
      beta-tubulin mRNAs were localized in the somata and proximal dendrites of SNB
      motoneurons. Removal of androgen by castration significantly reduced the
      expression levels of both beta-actin and beta-tubulin mRNAs in the SNB
      motoneurons, whereas the changes were prevented by testosterone treatment. In
      contrast, castration or testosterone treatment induced little or no change in the
      expression levels of these mRNAs in the much less androgen-sensitive motoneurons
      of the retrodorsolateral nucleus (RDLN). These results suggest that androgen
      regulates the expression of beta-actin and beta-tubulin genes in the SNB
      motoneurons and may provide evidence for the molecular mechanisms of hormonally
      induced neuronal plasticity in the SNB motoneurons.

PMID- 7729805
TI  - Interactions of estrogen with the neurotrophins and their receptors during neural
      development.
AB  - We are interested in examining mechanisms underlying estrogen actions during
      neuronal differentiation in the central nervous system (CNS). Our research has
      focused on one possible mechanism, the developmental interactions between
      estrogen and the neurotrophins (nerve growth factor [NGF], brain derived
      neurotrophic factor [BDNF] and neurotrophin-3 [NT-3]). Using combined isotopic
      and non-isotopic in situ hybridization, we found that neurons in developmental
      estrogen targets (e.g., the cerebral cortex), co-localized mRNAs for the
      neurotrophins (NGF or BDNF) with their cognate receptors (p75NGFR [the pan
      neurotrophin receptor] and trkA or trkB [the tyrosine kinase receptors]),
      suggesting a localization of neurotrophin-autocrine loops to these estrogen
      sensitive neurons. In contrast, the basal forebrain, which is estrogen-sensitive
      in the adult and during development, only expressed neurotrophin receptor mRNAs,
      suggesting that this region was not an autocrine neurotrophin target. We examined
      the potential for developmental estrogen-neurotrophin interactions, using a model
      neurotrophin-sensitive system, i.e., differentiating PC12 cells. NGF
      significantly increased estrogen receptor density in PC12 cells. Reciprocally,
      estrogen up-regulated trkA mRNA and transiently down-regulated p75NGFR mRNA,
      suggesting that estrogen may increase the efficiency of NGF binding in PC12
      cells. Similar estrogen-dependent regulation of NGF receptor mRNAs were also
      observed in the adult dorsal root ganglia, suggesting that estrogen may regulate
      NGF sensitivity in adult neurotrophin targets as well. Such estrogen-neurotrophin
      interactions may have an important role during differentiation and in the adult,
      following injury.

PMID- 7729806
TI  - Estrogen rapidly induces c-jun immunoreactivity in rat striatum.
AB  - Estrogen has been reported to exert rapid effects on the function of neurons
      located in various brain regions, including those where classical estrogen
      receptors are not abundant, such as the striatum. The mechanism underlying these
      actions is not well understood, but does not appear to involve classical estrogen
      receptor-mediated genomic mechanisms. Estrogen has also been shown to regulate
      expression of immediate-early gene products in many tissues. In the present
      study, immunohistochemical methods were used to determine whether estrogen
      modulates the appearance of c-jun immunoreactivity (IR) in the striatum of rats.
      Administration of estradiol (100 micrograms/rat) to ovariectomized rats for 15
      min induced a rapid and transient increase in c-jun-IR in the dorsomedial
      striatum and the core region of the nucleus accumbens. These data suggest that c
      jun may serve as one of the rapidly responding mediators of estrogen action in
      the striatum and nucleus accumbens.

PMID- 7729807
TI  - Sex hormone modulation of neural development in vitro.
AB  - The sex hormonal milieu during human and primate development is thought to
      influence adult cognition, perception, and behavior. Similarly in the rat, the
      neonatal sex hormonal milieu dictates adult behavior, as well as patterns of
      neural organization within the CNS. Specifically, estrogen and androgen alter
      neurite outgrowth, neuritic spine development, and synaptogenesis in the limbic
      system and spinal cord. To examine specific molecular/cellular effects of sex
      hormones on neurons, in vitro models were developed, using the PC12 cell line.
      Wild-type cells (PC12-WT) were stably transfected either with an expression
      vector coding for the human estrogen receptor (ER), androgen receptor (AR), or
      with a control vector. Resultant clones were isolated, screened for incorporation
      of vector and expression of ER or AR mRNA and protein, and analyzed for
      morphologic responses to estrogen and androgen, respectively. PC12-WT, NEO9 (ER
      negative, AR-negative), SER8 (ER-positive, AR-negative), and AR8 (ER-negative, AR
      positive) cells were exposed to nerve growth factor and graded doses of estradiol
      or dihydrotestosterone (DHT) for 2 days. In SER8 cells, estradiol led to dose
      dependent increases in the frequency of neurite outgrowth, spine development, and
      interneuritic connectivity. Estradiol increased the frequency of gap junction
      frequency and length, and functional dye-coupling in SER8 cells. Conversely, in
      AR8 cells, DHT induced a dose-dependent increase in mean neurite length, branch
      order, and neuritic field area, while neurite branch segment length and soma area
      were unaffected. These results suggest that SER8 and AR8 cells in vitro
      recapitulate various sex hormonal effects on neurons in vivo. Estrogen and
      androgen appear to induce inherent neural morphologic programs in which androgen
      increases neurite arborization and the receptive field of individual cells,
      increasing the likelihood for intercellular communication, while estrogen
      actually induces this communication, in the form of spines, synapses, and gap
      junctions. Thus estrogen and androgen act in different but complementary ways to
      modulate neural development and organization.

PMID- 7729808
TI  - Steroid hormone actions on the brain: when is the genome involved?
AB  - It has become customary to distinguish between so-called "genomic" actions of
      steroid hormones involving intracellular receptors and "non-genomic" effects of
      steroids that involve putative cell surface receptors. Whereas there is no doubt
      that this distinction has considerable validity, it does not go far enough in
      addressing the variety of mechanisms that steroid hormones use to produce their
      effects on cells. This is because cell surface receptors may signal changes in
      gene expression, while genomic actions sometimes affect neuronal excitability,
      often doing so quite rapidly. Moreover, steroid hormones and neurotransmitters
      may operate together to produce effects, and sometimes these effects involve
      collaborations between groups of neurons. As illustrations, evidence is reviewed
      in this article that a number of steroid actions in the hippocampus involves the
      co-participation of excitatory amino acids. These interactions are evident for
      the regulation of synaptogenesis by estradiol in the CA1 pyramidal neurons of
      hippocampus and for the induction of dendritic atrophy of CA3 neurons by repeated
      stress as well as by glucocorticoid injections. In addition, neurogenesis in the
      adult and developing dentate gyrus is "contained" by adrenal steroids as well as
      by excitatory amino acids. In each of these three examples, NMDA receptors are
      involved. These results not only point to a high degree of interdependency
      between certain neurotransmitters and the actions of steroid hormones but also
      emphasize the degree to which structural plasticity is an important aspect of
      steroid hormone action in the adult as well as developing nervous system.

PMID- 7729809
TI  - Steroid modulation of pulsatile LHRH release in the rhesus monkey.
AB  - Studies using push-pull perfusion of the stalk-median eminence (S-ME) in
      ovariectomized adult monkeys indicate that input of neuropeptide Y (NPY) neurons
      is an important modulator for the pulsatility of LHRH release: (1) NPY release in
      the S-ME was pulsatile; (2) NPY pulses occurred coupled to LHRH pulses, with NPY
      pulses preceding LHRH pulses; and (3) infusion of NPY into the S-ME stimulated
      LHRH release in a dose-responsive manner; whereas (4) infusion of a specific
      antiserum to NPY into the S-ME suppressed LHRH pulses. Further studies suggest
      that NPY neurons may mediate the action of steroid hormones. While treatment with
      a small dose of estrogen did not affect the coupling of NPY and LHRH pulses, it
      enhanced the sensitivity of LHRH release in response to NPY by 10,000-fold.
      Progesterone treatment 24 hr after estrogen induced an increase in LHRH release
      followed by an LH surge: Progesterone increased the pulse frequencies of both NPY
      release and LHRH release, maintaining the tight coupling of the pulses, while
      increasing LHRH pulse amplitude, but not NPY pulse amplitude. A parallel role of
      norepinephrine (NE) neurons in the modulation of pulsatile LHRH release was also
      observed indicating that more than one neuronal system can be simultaneously
      involved in the regulation of LHRH release and the action of ovarian steroids.
      Moreover, in the modulation of LHRH pulses, NPY and NE neurons were independent
      of each other. Further studies indicate that the LHRH neurosecretory system in
      the sexually immature monkey was insensitive to estrogen. This insensitivity
      appeared to be due to the tonic inhibition of pulsatile LHRH release by gamma
      aminobutyric acid (GABA) neurons through GABAA receptors. These results suggest
      that in vivo LHRH release is modulated by NPY, NE, and GABA neuronal inputs which
      mediate the action of steroid hormones.

PMID- 7729810
TI  - Bicuculline infusions advance the timing of luteinizing hormone surge in
      proestrous rats: comparisons with naloxone effects.
AB  - The role of GABA neurons in the control of the surge of LH secretion was
      investigated by examining whether GABAA receptor antagonist bicuculline (BIC)
      infusion prior to the LH surge could advance the timing of the proestrous surge
      in the rat. The effect of the opioid receptor antagonist naloxone (NAL) was also
      examined for comparison. Female rats in proestrus were iv infused with NAL (2 or
      5 mg/hr) or BIC (50 mg/kg/hr) for a 3-hr (1000-1300 hr) period during which blood
      samples were collected at 6-min intervals through an intraatrial cannula in
      freely moving rats. The animals that received infusion were bled again over a 7
      hr period (1400-2000 hr) at 1-hr intervals. NAL infusions at 2 mg/hr induced an
      increase in pulsatile LH secretion, but did not affect the timing, magnitude, and
      duration of the LH surge. NAL infusions at 5 mg/hr not only induced a greater
      increase in pulsatile LH secretion but also resulted in a pronounced LH surge
      prematurely. In contrast, during BIC infusion, no significant changes in LH
      secretion were seen until 1200 hr, but afterward a rapid and sharp rise in LH
      secretion occurred, suggesting the premature LH surge. These results are
      consistent with the hypothesis that the tonic LH secretion is sensitive to NAL,
      but not to BIC, whereas the surge of LH secretion is sensitive to barbiturates
      that have been known as the activator of GABAA receptor complex. Therefore, we
      suggest that there is a LHRH surge generator, distinct from the pulse generator,
      in the brain, and it has GABA neurons in its circuitry.

PMID- 7729811
TI  - Gonadal steroid hormones and hypothalamic opioid circuitry.
AB  - Endogenous opioid peptides derived from several gene families are localized
      within hypothalamic regions known to be involved in the regulation of
      reproduction. For example, the proenkephalin gene products, met- and leu
      enkephalin, and the proopiomelanocortin (POMC) gene product, beta-endorphin, are
      found in the rat medial preoptic area (MPOA). Moreover, the expression of these
      peptides and their receptors varies across the estrous cycle in the female rat.
      We have examined the gonadal steroid regulation of mu-opiate receptors and opioid
      peptides in the MPOA, and POMC mRNA expression in neurons that innervate the
      MPOA. mu-Opiate receptors in the MPOA are sexually dimorphic and gonadal steroid
      hormone-dependent. Hormonal priming of ovariectomized rats with estrogen and
      progesterone (P) upregulates MPOA mu-receptors 27, but not 3, hr after P
      treatment. Inhibition of protein synthesis during the first 6 hr after P prevents
      receptor upregulation. The density of beta-endorphin fibers in the MPOA also
      increases following hormone treatment, and POMC mRNA expression in neurons that
      innervate the MPOA is induced by hormone treatment beginning 13 hr after P
      treatment. This delayed response might be ubiquitous among POMC neurons, as those
      innervating the median eminence also exhibit increased POMC mRNA expression along
      a similar time course. The results suggest that hormonal feedback regulates
      opioid peptides which act at mu-receptors in the MPOA to influence reproductive
      behavior and cyclicity. These opioid functions represent an important component
      in the complex regulatory processes which control reproduction.

PMID- 7729812
TI  - Estrogen-induced changes in the neural impulse flow from the female rat preoptic
      region.
AB  - Electrical stimulation of the medial preoptic area (MPO) interrupted the lordosis
      reflex, the major receptive component of female rat sexual behavior, without
      interfering with proceptivity. In contrast, axon-sparing MPO lesions with a
      neurotoxin enhanced lordosis and diminished solicitatory behavior. The MPO effect
      on the lordosis reflex was mediated by its projection to the ventral tegmental
      area (VTA) because electrical stimulation of the VTA had a similar effect. In the
      urethane-anesthetized rats, electrical stimulation of the VTA elicited antidromic
      action potentials in neurons in the core of the MPO. In the ovariectomized
      females and neonatally castrated males, but not in the androgenized females,
      estrogen increased thresholds and prolonged refractory periods for the antidromic
      activation. Thus the neural effect of estrogen was limited to those animals that
      showed lordosis in the presence of this steroid. Estrogen also inhibited neurons
      in the dorsal part of the MPO, which project to the midbrain locomotor region
      (MLR), but had an opposite excitatory effect on MLR-projection neurons in the
      medial part of the lateral preoptic area (mLPO). Estrogen may therefore enhance
      lordosis by reducing neural impulse flow from the MPO to the VTA. A reduced MPO
      output to the MLR, combined with an augmentation of the mLPO effect, may
      culminate in increased locomotion in the female rats in estrus, because the MPO
      suppresses locomotor activity whereas the mLPO facilitates it.

PMID- 7729813
TI  - Genomic and non-genomic actions of progesterone in the control of female hamster
      sexual behavior.
AB  - Progesterone (P) in both the ventromedial hypothalamus (VMH) and the ventral
      tegmental area (VTA) is necessary to facilitate sexual receptivity in estrogen
      primed hamsters. The mechanism of P may be different in the VMH and VTA, as there
      are many intracellular progestin receptors (PR) in the VMH but few in the VTA.
      Progesterone conjugated to bovine serum albumin (P-3-BSA) does not bind well to
      intracellular PR or permeate the surface of neuronal membranes. However, VTA
      application of P-3-BSA rapidly increases sexual receptivity if P has been applied
      earlier to the VMH. P-3-BSA is ineffective when applied to the VMH. The membrane
      limited effect of P may be related to the ability of some progestins to modulate
      the GABAA-benzodiazepine receptor complex (GBRC). We have found that infusions of
      a GABAA agonist, muscimol, into the VTA enhance and a GABAA antagonist,
      bicuculline, inhibit receptivity. Because P itself is not highly effective at the
      GBRC, and since the most potent modulators of the GBRC, the 5 alpha-reduced
      progestins, do not bind well to PRs, progestin metabolites were applied to the
      VTA. Only the potent GBRC modulators facilitated sexual receptivity when applied
      to the VTA concurrent with P to the VMH. The reverse treatment, with a progestin
      metabolite implanted into the VMH, was ineffective. VTA infusions of an inhibitor
      of 5 alpha-reductase also attenuated behavioral estrus in hamsters.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7729814
TI  - Gene expression of progesterone receptor isoforms in the rat brain.
AB  - Progesterone receptors (PRs) are known to exist in two forms: a larger molecular,
      form B, and a smaller one, form A. Rat PR cDNA corresponding to the region around
      the translation-initiation site (ATGB) of the putative PR form B mRNA was cloned,
      together with cloning of steroid-binding domain of the PR forms A and B. An
      imperfect "estrogen responsive element," GGTCG*** TGACT, was located around ATGB
      of the rat PR cDNA. The distribution of PR mRNA-containing neurons was mapped in
      the female adult rat brain by in situ hybridization, which was largely in
      agreement with that of PR proteins. Differential intracerebral distribution of
      the mRNAs, measured by the quantitative RT-PCR Southern blotting assay, was found
      between the total (A+B) and form B mRNA levels, indicating possible distinct
      mechanisms responsible for regulation of the expression of the PR mRNAs. A region
      specific and stage-related gene expression of form B seems predominantly to be
      "turned on" first around birth, followed by that of form A around Days 8-12. The
      postnatal developmental pattern of PR form B mRNA in the cerebral cortex
      resembled that of the PR proteins. Noninducibility of the cortical PR by estrogen
      might be ascribable to the predominance of form B mRNA, which was reported to
      have little or no estrogen inducibility. A missmatch existed between PR from A
      and its mRNA levels, suggesting some impairment of the synthesis of form A.
      Thyroid hormone may be a regulator of gene expression of the receptor in the
      developing cortex.

PMID- 7729815
TI  - Gonadal steroid hormone receptors and sex differences in the hypothalamo
      pituitary-adrenal axis.
AB  - The rapid activation of stress-responsive neuroendocrine systems is a basic
      reaction of animals to perturbations in their environment. One well-established
      response is that of the hypothalamo-pituitary-adrenal (HPA) axis. In rats,
      corticosterone is the major adrenal steroid secreted and is released in direct
      response to adrenocorticotropin (ACTH) secreted from the anterior pituitary
      gland. ACTH in turn is regulated by the hypothalamic factor, corticotropin
      releasing hormone. A sex difference exists in the response of the HPA axis to
      stress, with females reacting more robustly than males. It has been demonstrated
      that in both sexes, products of the HPA axis inhibit reproductive function.
      Conversely, the sex differences in HPA function are in part due to differences in
      the circulating gonadal steroid hormone milieu. It appears that testosterone can
      act to inhibit HPA function, whereas estrogen can enhance HPA function. One
      mechanism by which androgens and estrogens modulate stress responses is through
      the binding to their cognate receptors in the central nervous system. The
      distribution and regulation of androgen and estrogen receptors within the CNS
      suggest possible sites and mechanisms by which gonadal steroid hormones can
      influence stress responses. In the case of androgens, data suggest that the
      control of the hypothalamic paraventricular nucleus is mediated trans
      synaptically. For estrogen, modulation of the HPA axis may be due to changes in
      glucocorticoid receptor-mediated negative feedback mechanisms. The results of a
      variety of studies suggest that gonadal steroid hormones, particularly
      testosterone, modulate HPA activity in an attempt to prevent the deleterious
      effects of HPA activation on reproductive function.

PMID- 7729816
TI  - Steroid hormone effects on gene expression, neuronal structure, and
      differentiation.
AB  - Steroid hormones modify several functions of the nervous system by altering
      expression of particular genes that are relevant for cell-to-cell communication,
      neuronal structure, and differentiation. There are many regions of the brain
      showing structural differences between male and female. These sexual dimorphisms
      are primarily based on cytological features of the nervous system brought about
      by the organizational action of sex steroid hormones. Glucocorticoids also have a
      great influence on neuronal survival and differentiation. First, in this paper
      the estrogen effect on the phenotypic changes of neurons in the preoptic area in
      vivo was described, particularly in the neuronal system of methionine-enkephalin
      and calcitonin gene-related peptide. Second, the tissue culture system for the
      preoptic area was developed and the estrogen effect on process extension
      associated with cytoskeletal changes was examined. Third, glucocorticoid
      suppression of the differentiation of adrenal chromaffin cells and
      transmitter/neuropeptide plasticity was studied in the dissociated culture
      system. The results suggest that steroids modulate neurotransmitters and
      neuropeptides expression along with the alteration of cell structures in a
      different manner in a tissue-specific pattern.

PMID- 7729817
TI  - Sex differences in the development of estrogen receptors in the rat brain.
AB  - The mechanisms involved in sexual differentiation of the brain remain
      incompletely defined. In mammals, testosterone secretion by the male during early
      development permanently alters the capacity of the brain to respond to
      circulating estrogen. In rats, this change in estrogen responsiveness is
      associated with a reduction in estrogen receptor (ER) levels in the
      periventricular region of the preoptic area (PVP), the medial preoptic nucleus
      (MPO), and the hypothalamic ventromedial nucleus (VMN) of the male. To determine
      whether these differences represent a response to early testosterone exposure or
      a secondary consequence of gonadal secretions at puberty, ER levels were measured
      by quantitative in vitro autoradiography in the brains of rats killed at
      intervals between 1-10 and 28-49 days of age. As early as 24 hr after birth, ER
      sex differences in the MPO and PVP are already quantitatively similar to those
      observed in adulthood. A sex difference in the VMN emerges later, between 5 and
      10 days of age. Differences between brain regions are also observed in the rate
      of ER development after the first week of life, ER concentrations in the PVP and
      MPO being close to adult levels within 1 day of birth, in contrast to the VMN
      where they increase markedly between Day 10 and adulthood in both sexes. These
      observations suggest that changes in ER concentrations may be one of the earliest
      hallmarks of brain sexual differentiation. Sex differences in ER in different
      brain regions may, however, be expressed asynchronously, providing a possible
      mechanism for variation in the duration of "critical periods" for testosterone
      mediated organization of specific CNS functions.

PMID- 7729818
TI  - Sex differences in the distribution and projections of testosterone target
      neurons in the medial preoptic area and the bed nucleus of the stria terminalis
      of rats.
AB  - Retrograde tracing was combined with steroid hormone autoradiography to
      investigate the projections of testosterone-target neurons in preoptic and limbic
      regions to the midbrain in male and female rats. Autoradiograms were prepared
      from the brains of male and female rats that had received an injection of a
      fluorescent retrograde tracer into the midbrain, and an intravenous injection of
      [3H]testosterone. Testosterone target neurons that project to the midbrain were
      abundant in the medial preoptic nucleus (MPN) and bed nucleus of the stria
      terminalis (BST) and were also observed in the ventromedial nucleus of the
      hypothalamus. Testosterone target neurons and testosterone target neurons that
      project to the midbrain were more abundant in the caudal half of the MPN compared
      to the rostral half. Moreover, male rats had more testosterone target neurons in
      the caudal MPN than female rats, and the number of testosterone target neurons in
      the MPN that project to the midbrain was higher in male than in female rats. Male
      rats also had more testosterone target neurons than females throughout the
      encapsulated subdivision of the BST. We hypothesize that sex differences in the
      neuronal connectivity of testosterone target neurons may underly sex specific
      behavioral responsiveness to androgens.

PMID- 7729819
TI  - Hormonal regulation of opioid peptide neurons in the anteroventral
      periventricular nucleus.
AB  - Steroid hormones provide a means of coordinating the activity of widespread
      neural systems that mediate endocrine, autonomic, and somatomotor aspects of
      reproductive processes that are essential for the propagation of mammalian
      species. Because these processes are quite different in each sex, the neural
      pathways that control them are also sexually differentiated. The anteroventral
      periventricular nucleus (AVPV) of the preoptic region occupies a nodal point in
      sexually dimorphic forebrain circuits and appears to play a critical role in
      regulating gonadotropin secretion. The AVPV contains sexually dimorphic
      populations of opioid peptide containing neurons that display different patterns
      of development and are differentially regulated in adult animals by gonadal
      steroids. Moreover, estrogen (ER) and progesterone (PR) receptors are expressed
      in AVPV neurons in a transmitter-specific way, and the expression of these
      nuclear transacting factors is differentially regulated by sex steroids. Thus,
      neurons in the AVPV show distinct patterns of hormonal regulation of gene
      expression, and distinct hormone receptor profiles.

PMID- 7729820
TI  - Membrane receptors for corticosterone: a mechanism for rapid behavioral responses
      in an amphibian.
AB  - This paper reviews evidence that, in some cases, steroid hormones rapidly
      modulate behaviors by binding to specific cell-surface receptors on neurons. The
      evidence comes from research with an amphibian model, Taricha granulosa. In
      Taricha, stress and corticosterone inhibit reproductive behaviors with a rapidity
      that is inconsistent with traditional models for steroid action (models in which
      intracellular steroid receptors function as transcription factors). A series of
      radioligand binding assay studies identified a corticosteroid receptor in
      neuronal membranes that appears to mediate the rapid behavioral responses in
      Taricha. Studies with various steroids showed a strong correlation between their
      potencies to inhibit the behavior and their potencies to inhibit corticosterone
      binding. Neurophysiological studies of caudal brainstem neurons found that
      corticosterone administration rapidly modulates neuronal activity and selectively
      suppresses sensory processing. Another series of studies provided evidence that
      this corticosterone receptor interacts with G proteins in neuronal membranes. The
      studies suggest that there are G protein-coupled receptors for corticosteroids
      that provide an alternative mechanism by which this hormone regulates brain
      functions and behaviors.

PMID- 7729821
TI  - Steroid hormone regulation and tissue-specific expression of the human GnRH gene
      in cell culture and transgenic animals.
AB  - In order to study the molecular mechanisms involved in the control of GnRH gene
      expression, the human GnRH gene was cloned and characterized. The gene was
      expressed in cells obtained from CNS tumors in transgenic mice generated
      utilizing 1131 bp of 5' flanking GnRH DNA fused to the simian virus 40 large T
      antigen. We have shown a stimulatory estrogen response element in the human GnRH
      gene by transient transfection studies. DNase I footprinting and an avidinbiotin
      DNA binding assay demonstrated that the human GnRH gene bound ER. The GN cell
      line was found to have nuclear ERs utilizing an 125I estradiol binding study and
      by in situ hybridization histochemistry. In order to study GnRH expression in
      vivo, either 5000 or 484 bp of GnRH flanking DNA was fused to the luciferase
      (Luc) reporter gene, and transgenic mice generated. Expression in the transgenic
      animals was found in the hypothalamus of animals bearing the -5000Luc transgene,
      but not in animals bearing the -484Luc transgene. The transgenic mice expressing
      the -5000Luc gene were gonadectomized resulting in a 20-30% increase in
      hypothalamic Luc expression in the males and a 65% increase in females, while
      mice who were gonadectomized and replaced with testosterone (males) or E2
      (females) showed a 50% decrease in Luc expression over control levels. Thus,
      these studies present in vitro evidence of E2 modulation of GnRH gene expression
      and an in vivo model in which sensitive studies of GnRH regulation and expression
      can be performed.

PMID- 7729822
TI  - Immunocytochemical detection of estrogen receptor in the facial nucleus of the
      newborn rat by three antibodies with distinct epitopes.
AB  - With the aid of three different antibodies, which recognize specific parts of the
      native estrogen receptor (ER) molecule, expression of the ER was confirmed not
      only in the hypothalamus but also in the ventromedial subdivision of the facial
      nucleus (n7) in neonatal (7-day-old) rats. In contrast, in 3-week-old prepubertal
      rats, the ER was detected in the hypothalamus and the amygdala, but not in the
      n7. Thus, the expression of ER in the n7 was shown to be a transient phenomenon.
      Transient appearance of ER has also been reported in the cerebral cortex of
      newborn rats and mice. Physiological significance of transient appearance of ER
      molecules in this subdivision is speculated as being related to the auditory
      function.

PMID- 7729823
TI  - Neuroactive steroid actions at the GABAA receptor.
AB  - Neuroactive steroids are a new class of steroids that do not interact with any of
      the classical cytosolic hormonal steroid receptors. The most well-documented
      examples are those that interact with the gamma-aminobutyric acidA (GABAA)
      receptor/chloride channel complex in the central nervous system. The GABAA
      receptors are known to contain allosteric modulatory sites for therapeutically
      useful drugs such as benzodiazepines (BZs) and barbiturates. The interaction of
      neuroactive steroids with the GABAA receptor is specific to a site on the
      receptor complex distinct from the benzodiazepine and barbiturate modulatory
      sites. Neuroactive steroids exist endogenously; the examples are metabolites of
      progesterone and deoxycorticosterone, 3 alpha-hydroxy-5 alpha-pregnane-20-one,
      and 5 alpha-pregnane-3 alpha, 21 alpha-dihydroxy-20-one, respectively, and their
      5 beta stereoisomers. The GABAA receptor agonist-like effects that these
      neuroactive steroids produce in vivo are similar, but not identical, to those of
      BZs and barbiturates. Representatives of all three classes of modulators are
      active as sedative-hypnotics, anticonvulsants, and anxiolytics in animal models.
      Because of the heterogeneity of GABAA receptors and their differential
      distribution in the brain, dissimilar in vivo pharmacological profiles displayed
      by BZs, barbiturates and neuroactive steroids are not surprising. Studies of
      neuroactive steroid interactions with the GABAA receptor revealed a unique subset
      of these steroids that modulate the receptor with limited efficacy. Another
      endogenously occurring progesterone metabolite, 5 alpha-pregnane-3 alpha,20 alpha
      diol, is an example of this subset of neuroactive steroids. At present, it is not
      clear whether the observed limited efficacy is due to receptor subtype
      selectivity, partial agonist activity or both.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729824
TI  - Sex-steroid receptor mechanism related to neuronal aromatase and the stigmoid
      body.
AB  - Recent immunohistochemical analyses of rat brains have established the presence
      of neuronal aromatase and stigmoid body in interfaces of a sex-steroid/brain
      axis. Aromatase P450-immunoreactive (AROM-I) neurons, which are present only
      during embryonic Day 16 to postnatal Day 2 (E16-P2), are found in the anterior
      medial preoptic nucleus, the periventricular preoptic nucleus, and the
      ventromedial hypothalamic nucleus. The largest AROM-I cell-group localized in the
      medial preoptico-amygdaloid neuronal arc (mPO-AM) shows a peak during E18-P2 and
      gradually diminishes after the perinatal days (but still retains the
      immunoreactivity in adults). In adults, other groups of AROM-I neurons emerge in
      the lateral septum, the central amygdaloid nucleus, and the bed nucleus of the
      stria terminalis. Male-predominant sex difference for aromatase expression has
      been detected at least in the young-to-adult mPO-AM, reflecting sexually distinct
      endocrine and behavioral responses in the rat reproductive functions. These
      results suggest the presence of distinct brain-aromatases with different
      regulatory systems. Neuronal aromatase may modulate development of sexual
      dimorphism in neonates and activation of reproductive functions in adults. The
      stigmoid bodies, marked by placental aromatase-associated antigen X-P2 (PAX)
      antiserum, are also frequent in the sex-steroid targets of rat brains and
      intimately coexist with estrogen receptors in the mPO-AM of young females. The
      neuronal inclusion, suspected as a RNA/protein conglomerate, appears to be
      induced by the decrease of androgen and/or the increase of estrogen, especially
      as a result of subneuronal aromatic switching into the estrogenous state. The
      neuronal aromatase and stigmoid body may play important roles in the pre- and
      post-receptor steps of subneuronal sex-steroids actions for brain sexual
      differentiation or induction of reproductive functions.

PMID- 7729825
TI  - Apolipoprotein E polymorphism and susceptibility to Alzheimer's disease.
AB  - Apolipoprotein E (apoE, protein; APOE, gene) plays an important role in
      lipoprotein metabolism by acting as a ligand for two specific cell receptors to
      mediate the uptake of apoE-containing lipoproteins by cells. The APOE gene,
      located on chromosome 19, exhibits a genetic polymorphism with three common
      alleles, APOE*2, APOE*3, and APOE*4, which show marked variation in their
      distribution among various ethnic groups. APOE polymorphism has a profound effect
      on interindividual variation in plasma cholesterol level in the general
      population, and this effect has made the APOE gene one of the most recognized and
      appreciated genes today. In addition to its pivotal involvement in lipoprotein
      metabolism, apoE is thought to participate in seemingly unrelated metabolic
      pathways, including the normal development of the nervous system and peripheral
      nerve regeneration after injury. The most dramatic and unexpected finding in this
      regard was made in early 1993, when it was reported that the presence of the
      APOE*4 allele is a significant risk factor for the development of late-onset
      familial Alzheimer's disease, a debilitating brain disorder. Since then, a number
      of studies have confirmed this provocative association and also have found that
      the APOE*4 allele is a major risk factor for Alzheimer's disease regardless of
      age at onset or family history. ApoE appears to contribute directly to the
      pathogenesis of Alzheimer's disease because it has been immunochemically
      localized in three defining lesions of the disease (extracellular amyloid
      plaques, intracellular neurofibrillary tangles, and vascular amyloid deposits).
      In this article I review current data about the association between APOE
      polymorphism and Alzheimer's disease and possible physiological mechanisms behind
      this association.

PMID- 7729826
TI  - VNTR DNA variation in Siberian indigenous populations.
AB  - The VNTR loci D7S104, D11S129, D18S17, D20S15, and D21S112 in three indigenous
      Siberian populations were analyzed to determine the populations' genetic
      structure. Using the Kolmogorov-Smirnov test, we found that the Siberian
      indigenous populations of Surinda and Sulamai are separated at the D11S129 locus
      (p < 0.05). However, the population of Poligus is genetically homogeneous
      compared with the villages of Sulamai and Surinda. Principal component plots for
      the sets of VNTR loci cluster the Siberian groups together, reflecting the
      homogeneity of these populations. An analysis of mean per locus heterozygosity
      versus the distance from the centroid of distribution suggests gene flow into
      Sulamai but little genetic exchange with Surinda and Poligus. Ultimately, the
      VNTR data reflect the genetic distinctiveness of the Kets and the Evenki.

PMID- 7729827
TI  - Quantitative variation in sets of triplets and quadruplets: a simulation.
AB  - A computer simulation was devised to generate realistic but large samples of
      twins, triplets, and quadruplets in each of the possible zygosity types. To
      validate the simulation, I used formulas proposed by Richter and Geisser (1960)
      to predict the mean value of the sum of squared deviations in each of three types
      of triplets and five types of quadruplets and to predict the distributions of the
      sums of squares in pure types (e.g., monozygotic and trizygotic triplets). Use of
      the formulas to predict distributions in sets of mixed type or to diagnose
      zygosity requires more advanced mathematical methods, but the simulation readily
      generates standard populations of all types of sets. If large enough numbers of
      real triplets or quadruplets ever become available to permit useful comparison
      with these standards or with the formulas, developmental peculiarities of the
      higher-order births might be revealed.

PMID- 7729828
TI  - Polymorphism of palmar main line terminations as an indicator of relationships
      among Sardinian linguistic groups of males.
AB  - Palmar main line modal types were used to calculate distance coefficients between
      Sardinian linguistic groups of males. By using correlation matrix analyses of the
      coefficients, we then determined whether or not the dermatoglyphic traits could
      reliably identify the biological relationships on the basis of the linguistic
      backgrounds of these groups. With Sanghvi's (X2)1/2 and by using palmar main
      lines both singly and together, we calculated dermatoglyphic distance matrices.
      Mantel tests of matrix correspondence showed that, by using C and D lines singly
      or all palmar main lines together, statistical significance between
      dermatoglyphic and linguistic distances can be obtained, even when the effect of
      geography is removed; there is no statistically significant correspondence
      between geographic and dermatoglyphic distance matrices, even when the effect of
      language is removed. Considering the historical and linguistic background, the
      results obtained by means of the Mantel test procedure, and the present
      dermatoglyphic differences in Sardinian linguistic groups of males, we can
      hypothesize that these groups were already genetically differentiated before the
      Romance languages and their respective dialects developed.

PMID- 7729829
TI  - Effect of occupation on menstrual cycle length: causal model.
AB  - The effect of occupational stress on menstrual cycle length was studied
      prospectively. The hypothesis that occupational stress has a direct or indirect
      effect on cycle length was tested using path analysis. Twice the number of women
      involved in active farm, craft, or household work had significantly longer cycle
      lengths than sedentary beedi workers and clerks. We conclude that occupational
      stress has a direct effect on menstrual cycle length and that that effect is
      similar to the effect of exercise on cycle length. The impact of longer cycles on
      fertility, fertility regulation, and natural family planning methods are also
      discussed.

PMID- 7729830
TI  - Differential reproductive success and body dimensions in Kavango males from urban
      and rural areas in northern Namibia.
AB  - We investigated differential sex-biased parental investment in relation to social
      status in 59 Kavango males from Rundu, the administrative and commercial center
      of the Kavango district in northern Namibia, and in 78 Kavango males from the
      rural areas around Rundu. Twenty-three body dimensions were used as indicators
      for the probands' social rank in the groups. The males from Rundu surpassed the
      males from rural areas in nearly all anthropometric features, but the urban males
      had significantly less offspring, especially fewer dead offspring. The
      association between the anthropometric variables and the number and sex of the
      offspring showed marked differences between the two proband groups. Although in
      the rural areas robust males had more children than smaller and leaner males, the
      taller and more robust males from Rundu had fewer offspring than smaller and more
      slender males. These results indicate that males from rural areas and males from
      urban areas follow different reproductive strategies.

PMID- 7729831
TI  - D1S80 locus variability in three Brazilian ethnic groups.
AB  - We have studied the hypervariable locus D1S80 in 75 white and 53 black Brazilians
      from Porto Alegre, a southern Brazilian population, and in 50 Brazilian Indians
      from the Xavante and Zoro tribes. Allele frequencies were significantly different
      among the three ethnic groups, mainly because of the higher frequencies of
      alleles *21, *22, *28, and *34 and the lower frequency of allele *18 in
      individuals of African ancestry and the higher frequencies of alleles *18 and *30
      in Brazilian Indians. In the Indian group a restriction in the number of alleles
      (7) and genotypes (15) was found. The data suggest that the D1S80 locus is a
      useful interpopulation marker. This is the first report of its allele frequencies
      in Amerindians.

PMID- 7729832
TI  - Electric field stimulation of excitable tissue.
AB  - This paper examines the transmembrane voltage response of an unmyelinated fiber
      to a stimulating electric field from a point current source. For subthreshold
      conditions, analytic expressions for the transmembrane potential, vm, are
      developed that include the specific effects of fiber-source distance, h, and time
      from the onset of the stimulus, T. Suprathreshold effects are determined for two
      examples by extending the analytical results with a numerical model. The vm
      response is a complex evolution in time, especially for small h, that differs
      markedly from the "activating function." In general, the subthreshold response is
      a good predictor of the wave shape of the suprathreshold vm, but a poor predictor
      of its magnitude. The subthreshold response also is a good (but not a precise)
      predictor of the region where excitation begins.

PMID- 7729833
TI  - A method for determining the driving currents for focused stimulation in the
      cochlea.
AB  - A pseudo-inverse technique has been applied to a lumped-element model of the
      first turn of an implanted cochlea of a guinea pig. The method calculates the
      currents necessary to focus or distribute stimuli in desired patterns across the
      location of the family of auditory nerve cells in the implanted ear. Studies in
      animals are being undertaken to validate the technique.

PMID- 7729834
TI  - Comparative simulation of excitation and body surface electrocardiogram with
      isotropic and anisotropic computer heart models.
AB  - Comparative simulations between isotropic and anisotropic computer heart models
      were conducted to study the effects of myocardial anisotropy on the excitation
      process of the heart and on body surface electrocardiogram. The isotropic heart
      model includes atria, ventricles, and a special conduction system, and is
      electrophysiologically specified by parameters relative to action potential,
      conduction velocity, automaticity, and pacing. The anisotropic heart model was
      created by incorporating rotating fiber directions into the ventricles of the
      isotropic heart model. The orientation of the myocardial fibers in the ventricles
      of the model was gradually rotated counterclockwise from the epicardial layer to
      the endocardial layer for a total rotation of 90 degrees. The anisotropy of
      conduction velocity and intracellular electric conductivity was included in the
      simulation. Comparative simulations of the normal heart, LBBB, and RBBB showed no
      significant differences between the two models in the excitation processes of the
      whole heart or in the body surface electrocardiograms. However, it was easier to
      induce ventricular fibrillation in the anisotropic model than in the isotropic
      model. The comparative simulation is useful for investigating the effects of
      myocardial anisotropy at the whole heart level and for evaluating limitations of
      the isotropic heart model.

PMID- 7729835
TI  - Distribution of aortic mechanical prosthetic valve closure sound model parameters
      on the surface of the chest.
AB  - It has been previously proposed that heart valve closure sounds can be modeled by
      a sum of decaying sinusoids, based on the hypothesis that the heart cavity, heart
      walls, major vessels, and other structures in the chest constitute a frequency
      selective linear acoustic system and this system is excited by the rapidly
      decelerating valve occluder. In this study, distribution of the parameters of
      this model for the second heart sound is investigated. For this purpose, heart
      sounds of 10 patients who have a St. Jude-type bileaflet mechanical heart valve
      prosthesis in aortic position are recorded. Recordings are performed at 12
      different locations on the surface of the chest. To reliably assign
      representative parameters to each recording site, signal averaging, model order
      selection, and a special filtration technique are employed. The results of the
      analyses are discussed in relation to the above hypothesis on the heart sound
      generation mechanism. It is observed that site-to-site variation of frequencies
      of modes does not exceed the accuracy limit of proposed analysis method, but
      energies of these modes vary on the surface of the chest, and as a result of
      statistical analysis, it appears that energy of some modes are significantly
      different between two recording sites.

PMID- 7729836
TI  - Multiple drug hemodynamic control by means of a supervisory-fuzzy rule-based
      adaptive control system: validation on a model.
AB  - A control device that uses an expert system approach for a two input-two output
      system has been developed and evaluated using a mathematical model of the
      hemodynamic response of a dog. The two inputs are the infusion rates of two
      drugs: sodium nitroprusside (SNP) and dopamine (DPM). The two controlled
      variables are the mean arterial pressure and the cardiac output. The control
      structure is dual mode, i.e., it has two levels: a critical conditions (coarse)
      control mode and a noncritical conditions (fine) control mode. The system
      switches from one to the other when threshold conditions are met. Different
      "controller parameters sets"-including the values for the threshold conditions
      can be given to the system which will lead to different controller outputs. Both
      control modes are rule-based, and supervisory capabilities are added to ensure
      adequate drug delivery. The noncritical control mode is a fuzzy logic controller.
      The system includes heuristic features typically considered by anesthesiologists,
      like waiting periods and the observance of a "forbidden dosage range" for DPM
      infusion when used as an inotrope. An adaptation algorithm copes with the wide
      range of sensitivities to SNP found among different individuals, as well as the
      time varying sensitivity frequently observed in a single patient. The control
      device is eventually tested on a nonlinear model, designed to mimic the
      conditions of congestive heart failure in a dog. The test runs show a highest
      overshoot of 3 mmHg with nominal SNP sensitivity. When tested with different
      simulated SNP sensitivities, the controller adaptation produces a faster response
      to lower sensitivities, and reduced oscillations to higher sensitivities. The
      simulations seem to show that the system is able to drive and adequately keep the
      two hemodynamic variables within prescribed limits.

PMID- 7729837
TI  - The dynamic response of the cat ankle joint during load-moving contractions.
AB  - The dynamic response of the cat's ankle joint during load-moving activation of
      the medial gastrocnemius was determined. Sinusoidal-input oscillations of ankle
      plantar flexion were performed by the muscle at frequencies ranging from 0.4 to 5
      Hz against a 10-N load acting via a cable through a pulley with a 2 cm radius.
      This was followed by sinusoidal muscle length changes against the same load while
      excluding the joint. The frequency responses of the two conditions were compared
      and decomposed in terms of their relative phase and gain, and best-fit pole-zero
      models to yield the dynamic model of the joint isolated from the muscle
      properties. The muscle displacement transfer function M(j omega) was
      characterized as two sets of double poles at 2.1 and 3.2 Hz, with a pair of zeros
      at 0.92 and 20 Hz, and pure time delay of 8 mS. The joint model J(j omega) was
      obtained by adding a pole at 5 Hz and a zero at 13 Hz. It was concluded that the
      ankle joint acts as a lag system, introducing significant increase in the phase
      lag between stimulus input and mechanical output without affecting the frequency
      dependent attenuation of gain. Average harmonic distortion was less than 5% in
      all cases. This particular finding reveals that, despite its inherently nonlinear
      mechanical characteristics, the joint introduces no degradation in the simplified
      linear behavior of the muscle-joint system. This model is useful in the design of
      systems employing electrical stimulation to restore movement to limbs paralyzed
      by spinal cord injury or stroke.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729838
TI  - Influence of flow pattern on the parameter estimates of a simple breathing
      mechanics model.
AB  - The first-order model of breathing mechanics is widely used in clinical practice
      to assess the viscoelastic properties of the respiratory system. Although simple,
      this model takes the predominant features of the pressure-flow relationship into
      account but gives highly systematic residuals between measured and model
      predicted variables. To achieve a better fit of the entire data set, an approach
      hypothesizing deterministic time-variations of model parameters, summarized by
      information-weighted histograms was recently proposed by Bates and Lauzon. The
      present study uses flow and pressure data measured in intensive care patients to
      evaluate the real potential of this approach in clinical practice. Information
      weighted histograms of the model parameters, estimated by an on-line
      identification algorithm, were first constructed by taking into account the
      parameter percentage standard deviations. Then, the influence of the respiratory
      flow pattern on the calculated histograms was evaluated by the Kolmogorov-Smirnov
      statistical test. The results show that the method gives good reproducibility
      under stable experimental conditions. In addition, for a given airflow waveform,
      an increase in respiratory frequency shifts the histograms representing time
      varying viscous properties strongly versus lower values, whereas it shifts the
      histograms representing time-varying elastic properties slightly versus higher
      values. On the other hand, the same histograms were highly dependent on the
      airflow waveform, especially for the viscous properties. Even in a limited
      experimental work, in all the conditions considered, the method provides results
      which agree well with the physiological knowledge of nonlinear and
      multicompartment behavior of respiratory mechanics.

PMID- 7729839
TI  - Echographic image mean gray level changes with tissue dynamics: a system-based
      model study.
AB  - In echography, several groups have reported a systematic decrease in the total
      backscattering intensity or image mean gray level during myocardial contraction
      with a minimum at end-systole and maximum at end-diastole. In order to
      investigate this phenomenon, we use a three-dimensional inhomogeneous continuum
      model to mimic the tissue as a collection of cells that scatter the acoustic wave
      due to their individual impedance. The mathematical analysis clearly shows the
      relationship between the mean gray level changes and the size, orientation, and
      deformation of the cells that compose the tissue, as well as the frequency of the
      transducer. Using a myocardial model example, the mean gray level changes
      reported in the literature during contraction are described in terms of changes
      in orientation and deformation of cardiac fibers. The model is simple and should
      set the ground for further study and analysis of speckle pattern changes during
      tissue motion.

PMID- 7729840
TI  - Application of linear and nonlinear time series modeling to heart rate dynamics
      analysis.
AB  - The linear autoregressive (AR) model is often used to investigate the
      pathophysiologic mechanisms controlling heart rate (HR) dynamics. This study
      implemented parametric models new to this field to determine if a more
      appropriate HR dynamics modeling structure exists. The linear AR and
      autoregressive-moving average (ARMA) models, and the nonlinear polynomial
      autoregressive (PAR) and bilinear (BL) models were fit to instantaneous HR time
      series obtained from nine subjects in the supine position. Model orders were
      determined by the Akaike Information Criteria (AIC). Model residual variance was
      used as the primary intermodel comparison criterion, with significance evaluated
      by a chi 2 distributed statistic. The BL model best represented the HR dynamics,
      as its residual variance was significantly (p < 0.05) smaller than that of the
      corresponding AR model for nine out of nine data sets. In all cases, the BL model
      had a smaller residual variance than either the ARMA or PAR models. The bilinear
      model was ineffective at data forecasting, however, we show that this cannot
      reflect BL model validity because poor prediction is inherent to the BL model
      structure. The apparent superiority of the nonlinear bilinear model suggests that
      future heart rate dynamics studies should put greater emphasis on nonlinear
      analyses.

PMID- 7729841
TI  - Coordinate system matching for neuromagnetic and morphological reconstruction
      overlay.
AB  - The overlay of functional and morphological images is an essential tool for
      advanced and improved functional diagnosis showing the correlation between
      spatial structures or lesions and functional areas. We present an improved
      coordinate system matching technique. The well known method of three orthogonal
      coils combined in one coilset for an angular-independent measure is validated for
      the use of first- or higher order gradiometers instead of magnetometers. The
      coilset localization procedure was modified with lock-in detection and current
      feedback for better long range sensitivity. Real measurements with the 31-channel
      Philips-MEG system have been carried out. A very good localization accuracy below
      the measuring area with deviations below 2 mm was found. For coordinate system
      matching, a 3-D cursor with surface images from segmented MR-data was implemented
      and an optimized, weighted least squares fit transformation algorithm between
      functional and morphological systems was developed. The resulting transformations
      consist of weighted shifts and best-fit rotations and lead to deviations of
      marker positions in the mm range, depending mainly on the spatial accuracy of the
      marker fixation.

PMID- 7729842
TI  - Detection of loss of cerebral vascular tone by correlation of arterial and
      intracranial pressure signals.
AB  - With the use of a laboratory model, arterial and intracranial pressure signals
      were obtained under conditions of intact regulation of cerebral blood flow and
      massive dilation. During elevated intracranial pressure and intact regulation,
      positive pressure inhalation appears to briefly occlude venous flow into the
      cranial sinuses during inspiration. As a result, the intracranial pressure and
      arterial pressure signals are not similar. In contrast, when maximal dilation
      causes failure of regulation of cerebral blood flow, the intracranial pressure
      signal is approximately proportional to the arterial pressure signal. Comparison
      of the cross-correlation function derived from the intracranial and arterial
      pressure signals to the autocorrelation function of the arterial signal reveals
      that the two correlation functions are: 1) different during intact regulation and
      2) nearly identical during dilation induced failure of regulation of cerebral
      blood flow.

PMID- 7729843
TI  - Latency measurement improvement of P100 complex in visual evoked potentials by
      FMH filters.
AB  - The ensemble average of Pattern Shift Visual Evoked Potentials (PSVEP) signals is
      seriously affected by random latency variations encountered in each individual
      sweep which is modeled as a continuous signal with linear segments and well
      shaped triangular peaks. This effect is causing the smoothed peaks of the
      averaged PSVEP waveforms. It is our objective to restore the degraded peaks and
      provide accurate information about their exact location. The method used is based
      on nonlinear filtering of the FIR-Median Hybrid (FMH) type and is recommended as
      a postfiltering process to the well-known averaging methods of recovering PSVEP
      signals from noise by time-locking to stimuli. The new technique, tested in
      signals from clinical observations, has proven very promising.

PMID- 7729844
TI  - Brain maturation estimation using neural classifier.
AB  - Quantitative electroencephalographic (EEG) signal analysis has revealed itself as
      an important diagnostic tool in the last few years. Through the use of signal
      processing techniques, new quantitative representations of EEG data are obtained.
      To automate the diagnosis, a problem of supervised classification must be solved
      on these. Artificial Neural Networks provide an alternative to more traditional
      classifier systems for this task. The objective of this paper is to perform a
      comparison between several classifiers in a particular problem, the brain
      maturation prediction. The data preprocessing/feature extraction process and the
      methodology for making the comparison are described. Performance of the methods
      is evaluated in terms of estimated percentage of correctly classified subjects.

PMID- 7729845
TI  - 46th Scientific sessions of the Cardiological Society of India. Jaipur, December
      1-4, 1994. Abstracts.

PMID- 7729846
TI  - HIV epidemic in Punjab.
AB  - A total of 58890 subjects were screened for HIV infection between June 1987 to
      December 1992. Out of these, 42776 were blood donors and only 9 were positive for
      HIV by ELISA; 2749 were foreign students and 35 were confirmed positive both by
      ELISA and Western blot. Out of the remaining high risk subjects, 141 of 13365
      were confirmed to be HIV positive with a cumulative positivity rate of 10.5 per
      thousand. Out of the 141 confirmed sero positives, 47 had full blown disease and
      25 were dead by the time of compilation of data. Thirty seven i.e., 24.6 per cent
      had acquired infection through unscreened blood/products/haemodialysis. Thus
      Punjab has shown a steady rise of HIV infection over the last five years and the
      incidence of blood borne infection is very high.

PMID- 7729847
TI  - Prevalence of antibodies to polioviruses & enteroviruses excreted by healthy
      children in Bombay.
AB  - A total of 132 healthy children between the ages one month and 12 yr were
      surveyed to determine the prevalence of antibodies to the three poliovirus
      serotypes. Among infants up to six months of age, 73.2, 85.4 and 56.1 per cent
      had antibodies to poliovirus types 1, 2 and 3, respectively. In children of age
      groups 7 months to 3 yr and above 3 yr, antibody prevalence to the three
      poliovirus serotypes was 90.2, 86.9 and 57.4, and 83.3, 96.7 and 76.7 per cent,
      respectively. Immunization coverage with three doses of OPV exceeded 85 per cent
      in children above 7 months of age. Low seroprevalence to type 3 poliovirus in the
      children was conspicuous. Of the 80 faecal samples studied from these children,
      24 (30%) were positive for virus. Among these isolates, 16 were poliovirus type 1
      and three type 2. Intratypic differentiation revealed that 15 of the 16
      poliovirus type 1 isolates were of wild origin. Two out of the three poliovirus
      type 2 isolates were of oral poliovaccine origin. Our data indicate that in spite
      of good vaccination coverage wild poliovirus type 1 circulation was endemic in
      Bombay and; that a large number of children were susceptible to poliovirus type 3
      infections.

PMID- 7729848
TI  - Rapid detection of Vibrio cholerae 0139 in faecal specimens by coagglutination.
AB  - We compared the conventional culture method with the coagglutination (CoA) test
      for detecting V. cholerae 0139 antigen in a 4 h faecal enrichment culture. The
      CoA test reacted positively in all 13 culture positive stool specimens from
      patients with clinical cholera and negatively in all 23 culture negative
      specimens from non-diarrhoeal healthy controls. The test also did not show cross
      reaction with V. cholerae 01 antigen or with any of the enterobacterial antigens
      of the coliforms. The CoA test was found to be technically simple, rapid and
      reliable in diagnosing V. cholerae 0139 infection.

PMID- 7729849
TI  - Colonization ability & intestinal pathology of rabbits orally fed with Vibrio
      cholerae O139 Bengal.
AB  - The colonization ability of a representative epidemic strain of V. cholerae O139
      Bengal was studied in the oral rabbit colonization model and the nature of
      colonization in the ileal and jejunal tissues was examined ultrastructurally.
      Results of the colonization study and ileal loop assay indicated that the strain
      proliferates and colonizes the small intestine of the rabbit mucosal surface.
      Further, the electronmicroscopic study revealed the disruptive effect of the
      strain on the apical membrane of the epithelial cells. The results of this study
      suggested that apart from colonization, invasion of the bacteria was important in
      the pathogenesis of V. cholerae O139 mediated infections.

PMID- 7729850
TI  - Outbreak due to Vibrio cholerae E1 Tor & serotype O139 in Yavatmal (Maharashtra)
      during June-July, 1994.
AB  - A total of 65 strains of V. cholerae were isolated during June-July 1994 at
      Yavatmal (Maharashtra). Of the 65 strains isolated, 62 were 01 El Tor Vibrios,
      while three were non 01 serotype 0139. The novel epidemic strain designated as
      0139 reported during the outbreak in 1993, has been supplanted by the usual El
      Tor Vibrio during the present outbreak while 0139 serotype has remained sporadic.

PMID- 7729851
TI  - Long-term preservation of streptococci.
AB  - Strains of 12 T types of group A streptococci preserved by sand desiccation and
      stored at 4 degrees to 10 degrees C were regularly sub-cultured to check their
      viability. For this, streptococci coated onto sand particles mixed with sterile
      sheep blood were inoculated into Todd-Hewitt broth with added blood and incubated
      for 24 to 48 h. Checking for viability every six months showed that group A
      streptococci could be preserved by this method for 21 yr. Our study shows that
      sand desiccation is a convenient and cheap method for the long-term preservation
      of streptococci in laboratories where other methods of preservation are not
      feasible on a regular basis.

PMID- 7729852
TI  - Dynamics of natural antibody responses to malaria parasite surface proteins in
      the intermediate rainfall zone of Sri Lanka.
AB  - Antibodies against repetitive epitopes on Plasmodium falciparum and P. vivax
      circumsporozoite (CS) proteins and epitopes on the 45 kDa and 185-200 kDa P.
      falciparum merozoite surface proteins were measured by radioimmunoassay in a two
      year longitudinal study in Nikawehera village located in the intermediate
      rainfall zone of Sri Lanka. The prevalence and concentrations of specific
      antibodies were in many, but not all instances, greater in adults than in
      children who were aged 7-15 yr at the beginning of the study. The concentrations
      and prevalence of antibodies were associated with malaria transmission levels
      previously determined from entomological and hospital admission data in the area.
      Antibody responses to epitopes on different P. falciparum antigens, two different
      epitopes within the 185-200 kDa merozoite surface protein and between the P.
      falciparum and P. vivax CS repeats were significantly correlated. Antibody
      concentrations against a conserved epitope in the 185-200 kDa protein were
      significantly higher in P. falciparum infected individuals than in non
      parasitaemic subjects. Antibody concentration and prevalences in Nikawehera were
      lower than at Weheragala, a site located 70 km away in the dry zone of Sri Lanka.
      It is postulated that lower levels of immunity in the population in areas such as
      Nikawehera, that are adjacent to more highly malaria endemic areas, may promote
      epidemics when conditions favour transmission.

PMID- 7729853
TI  - Protein cross-linking during oxidative denaturation of methaemoglobin.
AB  - Incubation of methaemoglobin in vitro for up to 4 h led to prominent cross
      linking of globin subunits. This process was inhibited by superoxide dismutase,
      catalase and metal-chelator like diethylenetriamine penta-acetic acid but not by
      scavengers of hydroxyl radicals. Methaemoglobin in solution produced superoxide
      radical. It is suggested that damage to globin subunits is mediated by active
      oxygen species like hydroxyl radical involving a 'site-specific mechanism'. The
      formation of microprecipitates in incubated samples of methaemoglobin was also
      inhibited by anti-oxidant enzymes and transition metal-chelator indicating again
      the involvement of oxygen free-radicals. Such oxidative denaturation of
      methaemoglobin progresses independent of any formation of hemichrome and may have
      important physiological significance.

PMID- 7729854
TI  - Delayed effects of exposure to organophosphorus compounds.
AB  - In a group of 34 industrial workers, chronically exposed to organophosphorus (OP)
      compounds, serum pseudocholinesterase activity was depressed significantly in the
      exposed group as compared to the control group. There was a significantly higher
      incidence of peripheral neuropathy among the workers exposed to OP compounds, as
      compared to the control group. Mild to profound sensorineural hearing deficits
      were detected in both the exposed and control groups. As the pre-exposure hearing
      status of the workers was not known and since many other factors can also cause
      pathological changes in the cochlear nerve, a definite conclusion about the
      ototoxic nature of the OP compounds could not be drawn.

PMID- 7729855
TI  - Formula allergy and intolerance.
AB  - There are two major types of adverse reactions in infant formulas: (1) formula
      allergy/hypersensitivity, which is an immunologic response, and (2) formula
      intolerance, which is a nonimmunologic response. Formula intolerance can occur in
      infants with an underlying congenital or acquired enzyme deficiency
      (disaccharidase deficiency, galactosemia, hereditary fructose intolerance). The
      clinical presentation, diagnosis, and treatment of both reactions are reviewed in
      this article. The appropriateness of the use of a variety of infant formulas is
      discussed. Guidelines for the prevention of allergic disease are described as
      well.

PMID- 7729856
TI  - Intestinal and hepatobiliary diseases in HIV-infected children.
AB  - Children with HIV disease and gastrointestinal disease should be evaluated for
      enteric pathogens. Bacterial, protozoal, and viral agents can cause chronic
      diarrhea, abdominal pain, gastrointestinal bleeding, and contribute to growth
      retardation. This article presents an approach to the evaluation of the HIV
      infected child with gastrointestinal symptoms. Therapeutic and nutritional
      interventions are discussed with emphasis on the multidisciplinary approach
      required to initiate successful management.

PMID- 7729857
TI  - Diagnosis of coeliac sprue in 1994.
AB  - The first accurate clinical description of coeliac sprue was made more than a
      century ago. This disease entity could be defined and objectively diagnosed only
      after its relationship to gluten intake was discovered and jejunal biopsy
      techniques were developed to demonstrate the typical "flat" small intestinal
      mucosa. Since then clinical and histopathologic improvement on gluten-free diet
      has remained a cornerstone for the diagnosis of coeliac sprue; however,
      controversies regarding the diagnostic criteria had existed. This article
      presents the clinical features and the major categories of investigation for the
      diagnosis of coeliac sprue.

PMID- 7729858
TI  - Hepatitis vaccines.
AB  - The 1980s represented a decade of breakthroughs for the development of hepatitis
      vaccines. Plasma-derived and then recombinant hepatitis B vaccines were developed
      and introduced, killed hepatitis A vaccine was developed, and the virologic tools
      were discovered with which to lay the groundwork for a vaccine against hepatitis
      C. Even as the focus of the 1990s shifts toward antiviral therapy of chronic
      viral hepatitis, we cannot afford to neglect the importance of prevention by
      vaccination. Better vaccines and improved vaccination strategies for preventing
      hepatitis A and B will continue to demand research investment, and the most
      meager toehold will have to be exploited and pursued aggressively if a practical,
      effective hepatitis C vaccine is to be developed.

PMID- 7729859
TI  - Fulminant viral hepatitis.
AB  - Fulminant viral hepatitis is the most dramatic and life- threatening complication
      of acute viral hepatitis. Although our understanding of the diverse agents
      capable of producing this syndrome has increased, effective, specific therapies
      are lacking. Liver transplantation as a therapeutic modality for this condition
      has been widespread application and underscored the need to improve our ability
      to predict outcome.

PMID- 7729860
TI  - Clinical manifestations of alpha 1-antitrypsin deficiency.
AB  - Alpha 1-antitrypsin deficiency is the most common genetic cause of liver disease
      in infants and children and is the most common genetic disease for which liver
      transplantation is indicated. This article presents the clinical manifestations,
      diagnosis, treatment, and pathogenesis of alpha 1-antitrypsin deficiency.

PMID- 7729861
TI  - The molecular basis of inherited disorders of the gastrointestinal and
      hepatobiliary tracts. An update on recent progress.
AB  - In this article, genetic disorders of the gastrointestinal and hepatobiliary
      tracts ranging from common to very rare are reviewed. The first portion of each
      section highlights the clinical manifestations of the disorder; the second and
      more detailed portion of each section discusses what is currently known about the
      biology and genetics of the disorder. The potential use of gene therapy to treat
      many of these disorders is also reviewed.

PMID- 7729862
TI  - Gastroesophageal reflux in children. Clinical manifestations, diagnosis, and
      therapy.
AB  - Gastroesophageal reflux (GER) is a common occurrence during infancy. Most
      children have physiologic reflux that is of little consequence and requires
      minimal intervention. Pathologic GER, characterized by irritability, apnea, poor
      weight gain, or respiratory compromise, often requires diagnostic evaluation and
      aggressive treatment. A framework to help the clinician to understand the
      pathogenesis, natural history, diagnostic testing, and therapy of this disorder
      is presented in this article.

PMID- 7729863
TI  - Ulcerative colitis and Crohn's disease in children. Diagnosis and management.
AB  - The foregoing discussion emphasizes the broad range of problems experienced by
      children and adolescents with chronic IBD. Approaches to the diagnosis and
      treatment of UC and CD in this distinctive population were provided herein.

PMID- 7729864
TI  - Dissociation of Escherichia coli heat-labile enterotoxin adjuvanticity from ADP
      ribosyltransferase activity.
AB  - The heat-labile enterotoxin (LT) of Escherichia coli is immunologically and
      physiochemically related to cholera enterotoxin. A number of studies have been
      performed to determine the relationship of the ADP-ribosylating enzymatic
      activity of these enterotoxins to toxicity and adjuvanticity. These studies have
      generally examined the effect of abolishing the ADP-ribosyltransferase activity
      of A1 by a variety of chemical or genetic manipulations. In every case, loss of
      enzymatic activity was associated with loss of biological activity and also with
      the ability of the molecules to function as oral adjuvants. Consequently, we
      explored an alternate approach to detoxification of LT without altering its
      adjuvanticity. Specifically, we generated a novel mutant form of LT by genetic
      modification of the proteolytically sensitive residues that join the A1 and A2
      components of the A subunit. This mutant contains a single amino acid
      substitution within the disulfide subtended region joining A1 and A2. This mutant
      toxin, designated LT(R192G), is not sensitive to proteolytic activation, has
      negligible activity on mouse Y-1 adrenal tumor cells, and is devoid of ADP
      ribosyltransferase activity. Nonetheless, LT(R192G) retains the ability to
      function as a mucosal adjuvant, increasing the serum immunoglobulin G (IgG) and
      mucosal IgA responses to coadministered antigen (OVA) beyond that achieved with
      administration of that antigen alone. Further, LT(R192G) prevented the induction
      of tolerance to coadministered antigen and did not induce tolerance against
      itself, as demonstrated by the presence of significant serum anti-LT IgG and
      mucosal anti-LT IgA antibodies in immunized mice.

PMID- 7729865
TI  - Cloning and characterization of the meningococcal polyphosphate kinase gene:
      production of polyphosphate synthesis mutants.
AB  - The pathogenic Neisseria species accumulate polyphosphate to levels between 10
      and 20% of their total phosphate content. However, the significance of this
      compound for the growth and pathogenicity of these species is not understood. A
      previous report (C.R. Tinsley, B.N. Manjula, and E.C. Gotschlich, Infect. Immun.
      61:3703-3710, 1993) describes the purification of polyphosphate kinase, the
      enzyme responsible for synthesis of polyphosphate, from Neisseria meningitidis
      BNCV. By use of probes based on the amino acid sequence of the purified enzyme,
      the structural gene ppk has been cloned and sequenced. The coding sequence is
      2,055 bp long and codes for a protein of 77.2 kDa. The open reading frame of the
      cloned gene was interrupted by the insertion of a kanamycin resistance cassette,
      and ppk mutants were obtained in both Neisseria gonorrhoeae and N. meningitidis
      by transformation with the recombinant plasmid. Amounts of polyphosphate in the
      ppk mutants were reduced to between 2 and 10% of wild-type levels. The mutants
      grew less vigorously than wild-type organisms in vitro and showed a striking
      increase in sensitivity to killing by human serum.

PMID- 7729866
TI  - Novel lipoprotein expressed by Neisseria meningitidis but not by Neisseria
      gonorrhoeae.
AB  - The ppk gene, which codes for the enzyme polyphosphate kinase in Neisseria
      meningitidis strain BNCV, is preceded by an open reading frame coding for a
      protein with a predicted size of 19.2 kDa with a typical lipoprotein signal
      sequence of 21 amino acids. The protein has significant homology to the N
      terminal portion of an outer membrane protein from Haemophilus somnus (J. Won and
      R. W. Griffith, Infect. Immun. 61:2813-2821, 1993). Sequencing of the same open
      reading frame from meningococcus strain M1080 predicted an almost identical
      protein. Antisera were raised against the lipoprotein, expressed in Escherichia
      coli as a fusion protein with glutathione S-transferase. The antisera reacted
      with meningococcal membrane fractions on a Western blot (immunoblot) but did not
      elicit complement-dependent bactericidal activity. Restriction enzyme digestion
      demonstrated conservation of this portion of the meningococcal and gonococcal
      chromosomes. However, antisera raised to the recombinant protein showed that the
      protein was absent from all strains of gonococcus tested. The sequences of the
      gene from several strains of Neisseria gonorrhoeae and N. meningitidis were
      compared and found to be almost identical, except that the coding sequences from
      all of the gonococcal strains were terminated prematurely as a result of a
      frameshift mutation. The significance of the remarkable conservation of these
      gonococcal genes is discussed.

PMID- 7729867
TI  - Direct anticryptococcal activity of lymphocytes from Cryptococcus neoformans
      immunized mice.
AB  - Assessment of the direct anticryptococcal activity of murine lymphocytes from
      both Cryptococcus neoformans-immunized and control mice was the focus of this
      investigation. We demonstrate that at a 2:1 effector cell-to-cryptococcal target
      cell ratio, effector cell populations comprised of alpha beta T-cell receptor
      positive T lymphocytes (98 to 99% CD3+) from C. neoformans-immunized mice
      inhibited the growth of cryptococcal cells better than similar populations of
      lymphocytes from nonimmunized control mice. Almost immediately after mixing of
      cryptococci with the effector cells, C. neoformans-lymphocyte conjugates were
      observed. The percentage of conjugates increased over the first 30 min of
      incubation and then remained constant over the next 1.5 h. T-lymphocyte-enriched
      populations from C. neoformans-immunized mice formed significantly greater
      percentages of conjugates with cryptococci than control T lymphocytes at each
      time period that assessment was made. For growth inhibition to occur, direct
      contact between the effector and target cells was necessary, as evidenced by
      abrogation of cryptococcal growth inhibition when lymphocyte and cryptococcal
      cell populations were separated by a porous membrane during the growth inhibition
      assay. Vital staining of cryptococci after incubation with the T-cell-enriched
      populations showed that the T lymphocytes killed the cryptococcal cells.

PMID- 7729868
TI  - Effects of immunization with Cryptococcus neoformans cells or cryptococcal
      culture filtrate antigen on direct anticryptococcal activities of murine T
      lymphocytes.
AB  - Immunizing CBA/J mice with intact Cryptococcus neoformans cells or with a
      cryptococcal culture filtrate antigen (CneF) induces an anticryptococcal delayed
      type hypersensitivity response. Recently, it has been shown that two
      phenotypically different T-cell populations are responsible for delayed-type
      hypersensitivity reactivity in mice immunized with intact cryptococcal cells,
      whereas only one of those populations is present in mice immunized with soluble
      cryptococcal antigens in complete Freund's adjuvant (CFA). The purpose of this
      study was to determine if differences occur with regard to direct
      anticryptococcal activity between T-lymphocyte-enriched populations from mice
      immunized with intact viable or dead cryptococcal cells and similar cell
      populations from mice immunized with the soluble cryptococcal culture filtrate
      antigen, CneF, emulsified in CFA. The percentage of lymphocytes which form
      conjugates with C. neoformans and the percentage of cryptococcal growth
      inhibition in vitro are greater with T-lymphocyte-enriched populations from mice
      sublethally infected with C. neoformans or from mice immunized with intact heat
      killed cryptococcal cells in the presence or absence of CFA than with lymphocyte
      populations from mice immunized with CneF-CFA. Enhanced anticryptococcal activity
      of T lymphocytes could be induced by immunizing mice with heat-killed C.
      neoformans cells of serotype A, B, C, or D as well as by immunizing with a
      similar preparation of an acapsular C. neoformans mutant but not by immunizing
      with CFA emulsified with CneF prepared from any one of the C. neoformans
      isolates. These data indicate that the soluble cryptococcal culture filtrate
      antigens do not induce the same array of functional T lymphocytes as whole
      cryptococcal cells.

PMID- 7729869
TI  - Detection of muramic acid in a carbohydrate fraction of human spleen.
AB  - In previous studies, we showed that peptidoglycan polysaccharides from anaerobic
      bacteria normally present in the human gut induced severe chronic joint
      inflammation in rats. Our hypothesis is that peptidoglycan from the gut flora is
      involved in perpetuation of idiopathic inflammation. However, in the literature,
      the presence of peptidoglycan or subunits like muramyl peptides in blood or
      tissues is still a matter of debate. We were able to stain red pulp macrophages
      in all six available human spleens by immunohistochemical techniques using a
      monoclonal antibody against gut flora-derived antigens. Therefore, these human
      spleens were extracted, and after removal of most of the protein, the
      carbohydrate fraction was investigated for the presence of muramic acid, an amino
      sugar characteristic for peptidoglycan. Using three different methods for
      detection of muramic acid, we found a mean of 3.3 mumol of muramic acid with high
      pressure liquid chromatography, 1.9 mumol with a colorimetric method for
      detection of lactate, and 0.8 mumol with an enzymatic method for detection of D
      lactate per spleen (D-lactate is a specific group of the muramic acid molecule).
      It is concluded that peptidoglycan is present in human spleen not as small
      muramyl peptides as were previously searched for by other investigators but as
      larger macromolecules probably stored in spleen macrophages.

PMID- 7729870
TI  - Selection of variant Borrelia burgdorferi isolates from mice immunized with outer
      surface protein A or B.
AB  - A nonclonal population of Borrelia burgdorferi N40 (passage 3) that survived
      protective immunity following challenge inoculation of outer surface protein
      (Osp) A- or B-hyperimmunized mice were characterized for the molecular basis of
      evasion of immunity. Two of six B. burgdorferi isolates, cultured from OspA
      immunized mice, had antigenic diversity in the carboxyl terminus of OspA and did
      not bind to the protective OspA monoclonal antibody designated IXDII. However,
      OspA-immunized mice challenged with these variants were fully protected.
      Moreover, B. burgdorferi isolates with a point mutation in ospB, which results in
      a truncated OspB that does not bind to protective OspB monoclonal antibody 7E6C,
      were frequently enriched after infection of OspB-immunized mice. These studies
      suggest that the incomplete efficacy of an OspA- or OspB-based vaccine may be
      partly due to immunomediated in vivo selective pressure, resulting in the
      persistence of some spirochetes that do not bind to protective antibodies.

PMID- 7729871
TI  - Helicobacter pylori requires an acidic environment to survive in the presence of
      urea.
AB  - The aim of this work was to study the significance of the urease enzyme in
      promoting Helicobacter pylori survival in various environments. A urease-positive
      H. pylori isolate, strain N6, and an isogenic urease-negative strain, strain
      N6(ureB::TnKm), were incubated in phosphate-buffered saline at a pH ranging from
      2.2 to 7.2 for 60 min at 37 degrees C in both the presence and the absence of 10
      mM urea. The number of CFU per milliliter in each solution, the pH of the
      bacterial supernatant, and the amounts of ammonia present in the solutions were
      measured. H. pylori N6 survived well in solutions with pH values ranging from 4.5
      to 7.0 in the absence of urea but survived in solutions only with an initial pH
      below 3.5 in the presence of urea. Neither strain grew after incubation in an
      alkaline environment. The pH of an acidic solution (i.e., 3.5) rose rapidly to
      8.45 in the presence of the wild-type strain and urea. The urease-negative mutant
      survived in solutions with pH values ranging from 4.5 to 7.2 irrespective of the
      presence of urea. Ammonia was present in significant amounts when H. pylori N6
      was incubated in the presence of urea. Strain N6 survived exposure to
      concentrations of ammonia as high as 80 mM. The acid environment of the stomach
      may be crucial for H. pylori survival in the presence of urea. H. pylori does not
      survive in the normal environment in the presence of urea because of the
      subsequent rise in pH rather than ammonia toxicity.

PMID- 7729873
TI  - Interleukin-5 is the predominant cytokine produced by peripheral blood
      mononuclear cells in alveolar echinococcosis.
AB  - An involvement of cellular immunity in alveolar echinococcosis is strongly
      suggested by the intense granulomatous infiltrations observed around the hepatic
      parasite lesions. However, the basis of cellular immunoregulation in patient with
      alveolar echinococcosis is poorly understood. The present report shows a
      comparative analysis of lymphoid cell function in peripheral blood mononuclear
      cells (PBMC) of 16 patients with alveolar echinococcosis and of healthy
      individuals. Our in vitro restimulation studies with crude Echinococcus
      multilocularis antigen demonstrated that PBMC from patients with alveolar
      echinococcosis were responsive to challenge with parasitic antigen as measured by
      lymphoid cell proliferation. In this system, we also evaluated cytokine
      expression at the gene and protein levels after stimulation with E.
      multilocularis antigen. Analysis of cytokine mRNA expression revealed distinct
      patterns of cytokine expression in patients and normal donors. By using reverse
      transcriptase PCR, we could demonstrate that the TH1 cytokine transcripts
      interleukin-2 (IL-2) and gamma interferon (IFN-gamma) are present in PBMC from
      patients with alveolar echinococcosis. Moreover, it was found that stimulation
      with E. multilocularis antigen induced or enhanced the expression of the TH2
      cytokine IL-3, IL-4, IL-10, and especially IL-5 mRNAs in PBMC from 13 of 16
      patients with alveolar echinococcosis. Two patients who were examined after
      radical surgery, as well as another patient with a stable course of the disease
      under continuous chemotherapy, were not able to generate the same pattern of
      cytokine response and had no evidence of IL-5 mRNA synthesis. In contrast to the
      frequent expression of TH2 cytokine mRNAs observed in patients with alveolar
      echinococcosis, PBMC cultures from normal donors showed prominent IL-2 and IFN
      gamma mRNA expression but weak IL-3, IL-4, and IL-10 mRNA expression. Most
      interestingly, IL-5 mRNA was substantially absent in PBMC from healthy
      individuals. In accordance with the mRNA studies, it was found that E.
      multilocularis antigen induced the secretion of large amounts of IL-5 and
      intermediate amounts of IFN-gamma in patients with alveolar echinococcosis,
      whereas large amounts of IFN-gamma and no or threshold amounts of IL-5 were
      detected in supernatants from healthy individuals. Collectively, the present
      study provides the first evidence that a TH2 immune response is gradually
      activated during the course of E. multilocularis infection, indicating a critical
      role for IL-5 in the manifestation of human alveolar echinococcosis.

PMID- 7729872
TI  - Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori
      stimulation in vitro.
AB  - Gastric infection with Helicobacter pylori activates a mucosal inflammatory
      response by mononuclear cells and neutrophils that includes expression of
      cytokines interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha, and
      IL-8. In this study, we analyzed the IL-8 response of human gastric cancer cell
      lines (Kato III, AGS, and MKN28) to H. pylori infection in vitro. IL-8 mRNA
      expression was detected by reverse transcription-PCR amplification of RNA
      extracted from epithelial cells after incubation with different H. pylori wild
      type and mutant strains, and IL-8 secretion was measured by an enzyme-linked
      immunosorbent assay. Exposure to viable H. pylori induced IL-8 mRNA and protein
      synthesis in all three gastric cell lines but not in nongastric epithelial cell
      lines. Heat-killed H. pylori and a crude cytotoxin preparation did not induce
      significant IL-8 secretion. IL-8 mRNA peaked between 2 and 4 h postinfection, and
      IL-8 protein production was maximal 24 h postinfection. Exposure of gastric
      carcinoma cells to other gastrointestinal bacteria, such as Pseudomonas
      aeruginosa, Campylobacter jejuni, and Escherichia coli, but not Campylobacter
      fetus, induced IL-8 synthesis. Wild-type strains that expressed the vacuolating
      cytotoxin (Tox+) and a cytotoxin-associated gene (cagA) product (CagA+) induced
      significantly more IL-8 than did CagA- Tox- strains. However, there was no
      decrease in IL-8 induction by isogenic mutants of CagA-, Tox-, or Cag- Tox-
      strains or by a mutant lacking the urease subunits. These results indicate that
      exposure to H. pylori and other gram-negative organisms that do not colonize the
      gastric mucosa induces IL-8 production by gastric carcinoma cells in vitro.
      Although the CagA+ Tox+ phenotype of H. pylori is associated with enhanced IL-8
      production by gastric cell lines, other bacterial constituents are clearly
      essential.

PMID- 7729874
TI  - Effect of polyclonal and monoclonal antibodies on surface properties of
      Streptococcus sobrinus.
AB  - In this study, the effect of antibody adsorption on physicochemical properties of
      Streptococcus sobrinus was studied. Bacteria were preincubated with polyclonal
      antibodies or with OMVU10, a monoclonal antibody (MAb) reactive with S. sobrinus.
      The zeta potentials and the hydrophobicity as determined by microbial adhesion to
      hydrocarbons were measured in potassium phosphate buffer with a pH ranging from 2
      to 9. S. sobrinus preincubated with polyclonal antibodies was positively charged
      at pH 2, 3, and 4 and had an isoelectric point at pH 4.8. Untreated S. sobrinus
      cells or cells preincubated with MAbs were negatively charged over the whole pH
      range. X-ray photoelectron spectroscopy showed a decrease in O/C and P/C ratios
      for bacteria preincubated with polyclonal antibodies. A combination of the pH
      dependent zeta potential and the X-ray photoelectron spectroscopy data of the
      overall chemical composition of the cell surface suggests that polyclonal
      antibody adsorption occurs through blocking of surface phosphate. The measurement
      of hydrophobicity by microbial adhesion to hydrocarbons revealed that S. sobrinus
      preincubated with polyclonal antibodies was hydrophobic (90% of the bacteria
      bound to hexadecane), whereas the controls were relatively hydrophilic. S.
      sobrinus preincubated with OMVU10 was found to be more hydrophobic than the
      controls at pH 5 and 7. Hydrophobicity as measured by water contact angles showed
      an increase in hydrophobicity when S. sobrinus was preincubated with polyclonal
      antibodies. The epitopes to which the antibodies are directed were visualized by
      immunogold labeling and electron microscopy. The results suggested that OMVU10 is
      reactive with only a few epitopes of the cell surface, whereas polyclonal
      antibodies were found to be reactive with many epitopes. In conclusion,
      adsorption of polyclonal antibodies was found to influence the overall
      physicochemical surface properties of the organism, probably by forming a coating
      over the whole cell surface. Adsorption of MAbs was more localized, which could
      explain their lesser influence on these surface properties.

PMID- 7729875
TI  - Extracellular neuraminidase production by a Pasteurella multocida A:3 strain
      associated with bovine pneumonia.
AB  - The properties of an extracellular neuraminidase produced by a Pasteurella
      multocida A:3 strain that was isolated in a case of bovine pneumonia were
      examined during growth in a defined medium. This enzyme (isolated from
      concentrated culture supernatants of P. multocida A:3) was active against N
      acetylneuramin lactose, human alpha-1-acid glycoprotein, fetuin, colominic acid,
      and bovine submaxillary mucin. Enzyme elaboration was correlated with the growth
      of the organism in a defined medium, with maximum quantities produced in the
      stationary phase. The enzyme was purified by a combination of ammonium sulfate
      fractionation, ion exchange on DEAE-Sephacel, and gel filtration on Sephadex G
      200. The purified neuraminidase possessed a specific activity of 9.36 mumol of
      sialic acid released per min per mg of protein against fetuin. The enzyme
      possessed a pH optimum of 6.0 and a Km of 0.03 mg/ml. The P. multocida A:3
      neuraminidase had a molecular weight of approximately 500,000 as estimated by gel
      filtration. The enzyme was stable at 4 and 37 degrees C for 3 h. Approximately
      75% of the neuraminidase activity was lost within 30 min at 50 degrees C. Greater
      than 90% of the enzyme activity was destroyed within 10 min at temperatures of >
      or = 65 degrees C. The P. multocida neuraminidase does not appear to be
      serologically related to the Pasteurella haemolytica A1 neuraminidase since
      antiserum prepared against the purified P. haemolytica enzyme did not neutralize
      the P. multocida enzyme.

PMID- 7729876
TI  - Purification and characterization of a low-molecular-mass T-cell antigen secreted
      by Mycobacterium tuberculosis.
AB  - A novel immunogenic antigen, the 6-kDa early secretory antigenic target (ESAT-6),
      from short-term culture filtrates of Mycobacterium tuberculosis was purified by
      hydrophobic interaction chromatography and anion-exchange chromatography by use
      of fast protein liquid chromatography. The antigen focused at two different pIs
      of 4.0 and 4.5 during isoelectric focusing, and each of these components
      separated into three spots ranging from 4 to 6 kDa during two-dimensional sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. The apparent differences in
      molecular masses or pIs of these isoforms were not due to posttranslational
      glycosylation. The molecular weight of the purified native protein was determined
      by applying gel filtration and nondenaturing polyacrylamide gel electrophoresis
      and found to be 24 kDa. ESAT-6 is recognized by the murine monoclonal antibody
      HYB 76-8, which was used to screen a recombinant lambda gt11 M. tuberculosis DNA
      library. A phage expressing a gene product recognized by HYB 76-8 was isolated,
      and a 1.7-kbp fragment of the mycobacterial DNA insert was sequenced. The
      structural gene of ESAT-6 was identified as the sequence encoding a polypeptide
      of 95 amino acids. The N terminus of the deduced sequence could be aligned with
      the 10 amino-terminal amino acids derived from sequence analyses of the native
      protein. N-terminal sequence analysis showed that the purified antigen was
      essentially free from contaminants, and the amino acid analysis of the antigen
      was in good agreement with the DNA sequence-deduced amino acid composition. Thus,
      the heterogeneities observed in the pI and molecular weight of the purified
      antigen do not derive from contaminating proteins but are most likely due to
      heterogeneity of the antigen itself. Native and recombinant ESAT-6 are
      immunologically active in that both elicited a high release of gamma interferon
      from T cells isolated from memory-immune mice challenged with M. tuberculosis.
      Analyses of subcellular fractions of M. tuberculosis showed the presence of ESAT
      6 in cytosol- and cell wall-containing fractions. Interspecies analyses showed
      the presence of ESAT-6 in filtrates from M. tuberculosis complex species. Among
      filtrates from mycobacteria not belonging to the M. tuberculosis complex,
      reactivity was observed in Mycobacterium kansasii, Mycobacterium szulgai, and
      Mycobacterium marinum.

PMID- 7729877
TI  - Endobronchial inflammation following Pseudomonas aeruginosa infection in
      resistant and susceptible strains of mice.
AB  - The early endobronchial inflammation induced by Pseudomonas aeruginosa infection
      varies in resistant and susceptible strains of mice. Mice of the DBA/2 strain are
      severely afflicted by the infection, with a high bacterial burden accumulating
      rapidly following inoculation and a high mortality rate occurring. Mice of the
      BALB/c strain are resistant to infection and clear the bacteria within 3 to 7
      days. Infection of (BALB/c x DBA/2)F1 hybrid mice showed that the resistance to
      lung P. aeruginosa infection is inherited as a dominant trait. Mice of the A/J
      and C57BL/6 strains were found to have an intermediate phenotype to Pseudomonas
      aeruginosa infection when compared with BALB/c and DBA/2 strains. The decrease in
      the bacterial load seen early after infection coincided with a steady and strong
      recruitment of inflammatory cells to the bronchoalveolar spaces of mice of the
      resistant BALB/c strain. On the other hand, the recruitment of inflammatory cells
      to the lungs of mice of the susceptible DBA/2 strain was deficient, resulting in
      the failure to control bacterial multiplication. Chemotactic factors,
      proinflammatory cytokines, and the number and function of recruited inflammatory
      cells may play major roles in the determination of the genetic resistance to lung
      infection with P. aeruginosa in a normal immunocompetent host.

PMID- 7729878
TI  - Role of tumor necrosis factor and gamma interferon in acquired resistance to
      Cryptococcus neoformans in the central nervous system of mice.
AB  - Although naive C.B-17 and BALB/cBy mice die of meningoencephalitis within 5 weeks
      of intravenous infection with an opportunistic strain of Cryptococcus neoformans,
      immunized mice express an acquired, CD4+ T-cell-dependent immunity and survive an
      intravenous infection. Infusion of lymphocytes from immune mice into severe
      combined immunodeficiency (SCID) mice renders these mice more resistant to
      cryptococcal brain infection than uninfused controls. We have investigated the
      role of gamma interferon (IFN-gamma) and tumor necrosis factor (TNF) in acquired
      resistance to C. neoformans. Neutralization of either IFN-gamma or TNF impaired
      resistance of immune BALB/cBy or C.B-17 mice to cryptococci. At 10 days
      postinfection, there were approximately 10 times as many yeast cells in the
      brains of mice treated with either anticytokine antibody as in the brains of mice
      treated with control antibody. Simultaneous neutralization of IFN-gamma and TNF
      further exacerbated infection. Neutralization of IFN-gamma or TNF also impaired
      resistance in immune lymphocyte-infused SCID mice, resulting in significantly
      higher yeast burdens in brains of cytokine-neutralized mice than in brains of
      controls. Concurrent neutralization of IFN-gamma and TNF rendered SCID recipients
      of immune cells equivalent to uninfused SCID mice with respect both to brain
      yeast burdens at 10 days and to survival. Anti-TNF treatment alone also curtailed
      survival. Histological examination of the brains of cytokine-neutralized mice
      revealed deficiencies in ability to focus inflammatory cells at brain lesions.
      These data demonstrate that both IFN-gamma and TNF are important mediators of
      acquired resistance to cryptococcal meningoencephalitis.

PMID- 7729879
TI  - Stimulation of interleukin-8 production in epithelial cell lines by Helicobacter
      pylori.
AB  - Following exposure to Helicobacter pylori cells, epithelial cell lines secreted
      interleukin-6 (IL-6) and IL-8 but not tumor necrosis factor alpha. Purified IL-6
      alone did not stimulate IL-8 production from the cell lines tested, indicating
      that IL-6 was not an intermediary in IL-8 induction. Enhanced IL-8 secretion
      occurred in a time- and dose-dependent manner. None of 12 antibiotics tested
      exhibited a significant effect on IL-8-inducing activity, suggesting that
      preformed antigens were responsible for stimulating IL-8 secretion in vitro. Live
      bacterial cells caused the highest level of stimulation. Proteinase-digested and
      heated (56 or 100 degrees C) cells had significantly reduced stimulatory
      activities. Purified H. pylori lipopolysaccharide, but not exopolysaccharide,
      stimulated low-level secretion of IL-8, but only at high concentrations, while a
      water-extracted H. pylori antigen preparation was strongly stimulatory for HEp-2
      cells. No reduction in IL-8-stimulatory activity was observed for H. pylori
      mutants negative for urease activity, production of a major lipoprotein, and
      motility. The noncytotoxic strain CCUG 915 stimulated lower IL-8 levels than
      other isolates. However, the otherwise isogenic cytotoxin-negative mutant 17874
      delta vacA (S. H. Phadnis, D. Ilver, L. Janzon, S. Normark, and T. U. Westblom,
      Infect. Immun. 62:1557-1565, 1994) had the same IL-8-stimulatory ability as the
      parent strain, suggesting that surface proteins other than the vacuolating
      cytotoxin are involved in IL-8 stimulation.

PMID- 7729880
TI  - Role of Salmonella typhimurium Mn-superoxide dismutase (SodA) in protection
      against early killing by J774 macrophages.
AB  - The Salmonella typhimurium gene for Mn-cofactored superoxide dismutase (sodA) was
      cloned by complementation of an Escherichia coli sodA sodB mutant for growth on
      minimal medium. Sequence analysis revealed an open reading frame of 618 bp
      encoding a polypeptide with 97% identity to E. coli SodA. A S. typhimurium sodA
      mutant was created by allelic exchange and tested for the ability to survive in
      the murine macrophage-like cell line J774. Growth of bacteria under iron-limiting
      conditions, inactivation of the Fur repressor, or expression of sodA from a
      plasmid resulted in increased resistance to early killing by J774 cells, which
      was abolished in the sodA mutant. These results suggest that resistance to the
      early oxygen-dependent microbicidal mechanisms of phagocytes involves the SodA
      gene product. The S. typhimurium sodA mutant was not significantly attenuated in
      mice, however, which suggests that resistance to early oxygen-dependent
      microbicidal mechanisms in vivo may play only a minor role in Salmonella
      pathogenesis.

PMID- 7729881
TI  - Molecular cloning of a serine proteinase inhibitor from Brugia malayi.
AB  - The antigens produced by the infective-stage larvae of filarial parasites are
      potentially important targets for a protective immune response. A major
      impediment to studies on the biochemistry and molecular biology of antigens from
      infective larvae is a lack of parasite material. By employing a reverse
      transcription PCR-based strategy which exploited the presence of a conserved 22
      nucleotide spliced leader sequence present at the 5' end of a proportion of
      nematode transcripts, spliced leader-containing cDNAs were amplified from the
      late-vector-stage larvae of the filarial nematode Brugia malayi. A major 1.4-kb
      PCR product was cloned into pBluescript. One of the PCR cDNA clones (BmY8)
      contained a 1,287-bp insert that encoded the first member of the serine
      proteinase inhibitor (serpin) superfamily to be described from nematodes. Reverse
      transcription PCR analysis of RNA isolated from different developmental stages of
      the parasite showed that transcription of the B. malayi serpin (Bmserpin) begins
      between days 8 and 9 of larval development within the insect vector and continues
      through to the adult and microfilarial stages. In immunoblot analyses of B.
      malayi somatic extracts, the native protein was estimated to have a molecular
      weight of 44,000. In immunoblots using excretory-secretory products from
      infective- and fourth-stage larvae, a single band with an estimated molecular
      weight of 75,000 was detected. A quantitative analysis of somatic extracts
      demonstrated that infective-stage larvae contained 10- to 16-fold-more Bmserpin
      than adults or microfilariae. Bmserpin was immunogenic in gerbils and was
      recognized strongly by sera from immunized animals. Bmserpin, which has the
      potential for modifying host defense responses, may play an important role in
      parasite survival during the early phase of vertebrate-stage development.

PMID- 7729882
TI  - Use of tissue culture and animal models to identify virulence-associated traits
      of Haemophilus ducreyi.
AB  - To identify virulence-associated properties of Haemophilus ducreyi, 34 strains of
      this sexually transmitted pathogen were evaluated for in vitro phenotypic
      characteristics of potential relevance to chancroid pathogenesis and for their
      ability to produce lesions in the temperature-dependent animal model for
      chancroid. Of the 34 strains tested, all but three produced a cytopathic effect
      on human foreskin fibroblasts (HFF) and all but six strains formed large
      microcolonies on HFF monolayers. A subset of 12 selected strains underwent more
      extensive analyses and, when evaluated for both their cytadherence kinetics and
      growth in the presence of HFF monolayers, it was found that several of these
      strains had a very limited ability to attach to HFF cells. When the same 12
      strains were tested in the temperature-dependent rabbit model, only the seven
      strains which were positive in all of these in vitro-based tests readily produced
      lesions. In contrast, the five strains that were noted to be deficient in one or
      more of the phenotypic characteristics scored in the in vitro systems did not
      produce lesions. This association between the traits measured in vitro and the
      ability to produce dermal lesions was significant (P = 0.0012). These results
      suggest that in vitro behavior may be used to predict the virulence potential of
      H. ducreyi strains. Moreover, the phenotypic characteristics described in this
      study are appropriate focal points for efforts to determine the molecular basis
      of the virulence of this pathogen.

PMID- 7729883
TI  - Efficacy of oral vaccination against the murine intestinal parasite Trichuris
      muris is dependent upon host genetics.
AB  - Oral vaccinations with Trichuris muris adult worm homogenate antigen with cholera
      toxin as the adjuvant were successful in both high-responder BALB/c and low
      responder C57BL/10 mice, resulting in high levels of protection against
      subsequent infection, but were ineffective in the low-responder B10.BR mice.
      Subcutaneous vaccination with antigen in Freund's complete adjuvant resulted in
      protection of all of these strains but was most effective in high-responder
      BALB/c and least effective in B10.BR mice. Oral vaccination resulted in a T.
      muris-specific intestinal immunoglobulin A response only in the two protected
      strains. High levels of serum immunoglobulin G1 antibody were induced by Freund's
      complete adjuvant vaccination in all cases. A relationship between vaccine
      efficacy, expulsion phenotype, and induced T-helper subset-associated cytokines
      (interleukin-5 and gamma interferon) was noted. It was concluded that effective
      vaccination against T. muris requires the induction of Th2 responses and that
      this can be achieved by both oral and parenteral administration of antigens.

PMID- 7729884
TI  - A plasmid-encoded regulatory region activates chromosomal eaeA expression in
      enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) organisms produce a characteristic
      histopathology in intestinal epithelial cells called attaching and effacing
      lesions. The eaeA gene is associated with attaching and effacing lesions and
      encodes intimin, a 94-kDa outer membrane protein. A 60-MDa plasmid, pMAR2, is
      essential for full virulence of EPEC strain E2348/69 (O127:H6). We have cloned
      sequences from pMAR2 that increase expression of the chromosomal eaeA gene as
      shown by increased alkaline phosphatase activity of an eaeA::TnphoA gene fusion,
      increased expression of the intimin protein, and increased production of eaeA
      mRNA. These sequences are called per for plasmid-encoded regulator. pMAR2-cured
      JPN15 containing cloned per sequences adheres to HEp-2 cells in greater numbers
      than JPN15 carrying the plasmid vector only. The cloned per sequences contain
      four open reading frames (ORFs) which have been designated perA through perD.
      Only perC can by itself activate expression of eaeA::TnphoA, although the levels
      of alkaline phosphatase activity seen with this ORF alone are considerably lower
      than those seen when all four ORFs are present. The molecular sizes of
      polypeptides predicted from perA, perB, perC, and perD ORFs are 24, 14.8, 10.5,
      and 9.4 kDa, respectively. The PerA predicted protein shares homology with
      members of the AraC family of bacterial regulators, but PerB, PerC, and PerD have
      no striking homology with previously described prokaryotic proteins. Our studies
      indicate that plasmid-encoded factors regulate the expression of eaeA and
      possibly genes encoding other outer membrane proteins and may be important for
      virulence of EPEC.

PMID- 7729885
TI  - Pulmonary paracoccidioidomycosis in resistant and susceptible mice: relationship
      among progression of infection, bronchoalveolar cell activation, cellular immune
      response, and specific isotype patterns.
AB  - Using the intraperitoneal route of infection, we demonstrated previously that
      A/Sn mice are resistant and B10.A mice are susceptible to Paracoccidioides
      brasiliensis infection. Since paracoccidioidomycosis is a deep systemic
      granulomatous disorder that involves primarily the lungs and then disseminates to
      other organs and systems, we herein investigated the course of the infection and
      the resulting immune responses developed by A/Sn and B10.A mice after
      intratracheal infection with P. brasiliensis yeast cells. It was observed that
      A/Sn mice develop a chronic benign pulmonary-restricted infection, whereas B10.A
      mice present a chronic progressive disseminated disease. A/Sn animals were able
      to restrict fungal infection to the lungs despite the increased fungal load at
      the beginning of the infection. This behavior was associated with low mortality
      rates, the presence of adequate and persistent delayed-type hypersensitivity
      reactions, oxidative burst by bronchoalveolar cells, and production of high
      levels of specific antibodies in which immunoglobulin G2a (IgG2a) and IgG3
      isotype titers were significantly higher than those observed in the susceptible
      mice. In contrast, B10.A animals showed a constant pulmonary fungal load and
      dissemination to the liver and spleen. This infection pattern resulted in high
      mortality rates, discrete delayed-type hypersensitivity reactivity, poorly
      activated or nonactivated bronchoalveolar cells, and production of specific IgG2b
      isotype titers significantly higher than those observed in the resistant mice at
      week 4 of infection. Thus, A/Sn and B10.A mice maintain the same resistance
      patterns as those observed previously with the intraperitoneal route of
      infection. Furthermore, the obtained results suggest that resistance to
      paracoccidioidomycosis is associated with T-cell, macrophage, and B-cell
      activities that are known to be mediated by gamma interferon.

PMID- 7729886
TI  - Local Th1-like responses are induced by intravaginal infection of mice with the
      mouse pneumonitis biovar of Chlamydia trachomatis.
AB  - A critical role for cell-mediated immunity (CMI) has been demonstrated for
      effecting the resolution of genital infections of mice infected intravaginally
      with the mouse pneumonitis biovar of Chlamydia trachomatis (MoPn). However,
      little is known about expression of CMI in the murine genital tract. The mouse
      MoPn model was used to examine CMI responses in the genital tract and associated
      lymph nodes during the course of infection. MoPn-specific lymphocytes were
      present in the genital mucosa, with the maximum level of proliferation in
      response to MoPn at 3 weeks postinfection. MoPn-stimulated cells secreting gamma
      interferon were also detected in the cells from the genital mucosa, but few
      interleukin-4-secreting cells were seen at any time postinfection, indicating the
      induction of a Th1-like response in the cells of the genital mucosa. The iliac
      node draining the genital tract was the major node stimulated as a result of a
      genital infection and exhibited a predominant Th1-like pattern of cytokine
      secretion as well. Mesenteric lymph node cells demonstrated poor proliferative
      responses to MoPn and few antigen-stimulated cytokine-secreting cells after the
      primary infection. However, 7 days after a second infection administered 50 days
      following the primary infection, there was a marked increase in both
      proliferative responses and the frequencies of MoPn-stimulated gamma interferon-
      and interleukin-4-secreting cells. These studies provided information regarding
      the local CMI response to MoPn in mice which may prove valuable in the
      development of vaccination strategies for the prevention of chlamydial genital
      infections.

PMID- 7729887
TI  - Heparin protects Opa+ Neisseria gonorrhoeae from the bactericidal action of
      normal human serum.
AB  - The pathobiological significance of lipooligosaccharide (LOS) and outer membrane
      opacity protein (Opa) changes in gonorrheal disease are poorly understood. We
      assessed variants of strain MS11mk with different LOS and Opa phenotypes for
      their liability to killing by normal human sera. LOS differences correlated with
      strikingly disparate susceptibilities to serum killing; LOSa variants were serum
      resistant, LOSb variants were serum sensitive, and sialylation of LOSb variants
      enhanced their survival (as reported previously). Opa phenotype had little
      influence on the killing of serum-sensitive LOSb cells that were incubated
      directly in normal human sera, but preincubation of Opa+ LOSb variants in heparin
      increased their serum resistance whereas Opa- LOSb variants showed no change.
      Some Opa proteins conferred slightly higher resistance than others, but heparin
      preincubation increased serum resistance for variants expressing each of seven
      Opa proteins. These in vitro phenomena may relate to conditions within the male
      urethra where sulfate-containing proteoglycans are abundant and where antibody
      and complement may transude from blood plasma. The results suggest that the
      selective advantage for Opa+ Neisseria gonorrhoeae bacteria observed in vivo may
      reflect their ability to utilize host cell components to resist killing by host
      defenses.

PMID- 7729888
TI  - Effect of salicylate on expression of flagella by Escherichia coli and Proteus,
      Providencia, and Pseudomonas spp.
AB  - Osmotic stress, salicylate, and Mar (multiple antibiotic resistance) mutation are
      known to block the expression of the OmpF porin. Since these conditions have also
      been shown to inhibit the expression of P and CFA fimbriae in Escherichia coli,
      we speculated that they might affect the expression of flagella as well.
      Hyperosmotic conditions have been shown to block the synthesis of flagellin and
      expression of flagella in E. coli (C. Li, C. J. Louise, W. Shi, and J. Adler, J.
      Bacteriol. 175:2229-2235, 1993). In the current study, sodium salicylate was
      found to inhibit the motility of E. coli, Proteus mirabilis, Proteus vulgaris,
      Providencia rettgeri, and Providencia stuartii in a reversible, concentration
      dependent manner. Swarming did not occur at 20 mM sodium salicylate. Salicylate
      also blocked the synthesis of flagellin in E. coli. Phenotypic Mar mutants of E.
      coli derived from motile strains were amotile. Flagella were markedly reduced as
      determined by scanning electron microscopy when P. mirabilis was grown in broth
      containing 20 mM salicylate. Salicylate had no apparent effect, however, on
      expression of a 40-kDa porin protein in P. mirabilis. This finding suggests that
      the noted effect of salicylate on Proteus spp. may be mediated through a
      mechanism other than porin production or that the Proteus porin may not be
      analogous to OmpF in E. coli. Salicylate decreased the motility of Pseudomonas
      cepacia but had no effect on Pseudomonas aeruginosa. The exact mechanism by which
      salicylate exerts its effect is not known, but it appears to be related to
      osmoregulation.

PMID- 7729889
TI  - Differential susceptibility of yeast and hyphal forms of Candida albicans to
      macrophage-derived nitrogen-containing compounds.
AB  - Candida albicans is a dimorphic fungus capable of transition from the yeast form
      (Y-Candida) to the hyphal form (H-Candida). Both Y-Candida and H-Candida are
      known to be growth inhibited by murine macrophages (M phi) in vitro. In the
      present report, we demonstrate that M phi exposed to interferon gamma (IFN-gamma)
      plus lipopolysaccharide (LPS) show enhanced anti-Y-Candida and anti-H-Candida
      activities. To further investigate the phenomenon, Y-Candida and H-Candida were
      assessed for susceptibilities to M phi-derived supernatants. Only the growth of H
      Candida, and not that of Y-Candida, is impaired by cell-free supernatants from M
      phi treated with IFN-gamma plus LPS. In contrast, no H-Candida growth inhibition
      occurs when supernatants from M phi exposed to IFN-gamma plus LPS in the presence
      of NG-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, are
      employed. Finally, supernatants from M phi incubated with sodium nitroprusside,
      an NO-generating agent, also show anti-H-Candida activity. In conclusion, these
      results indicate that H-Candida but not Y-Candida is susceptible to extracellular
      antifungal mechanisms employed by M phi, which likely involve stable nitrogen
      containing compounds.

PMID- 7729890
TI  - Regulation of macrophage activation and human immunodeficiency virus production
      by invasive Salmonella strains.
AB  - Salmonellae possess the ability to adhere to and invade macrophages and in so
      doing trigger a number of intracellular events that are associated with cellular
      activation. As an initial approach to defining the mechanisms by which invasive
      salmonellae alter macrophage function, we have explored the impact of Salmonella
      infection on the production of human immunodeficiency virus (HIV) in U1 cells, a
      promonocytic cell line latently infected with the virus. Infection of U1 cells
      with a pathogenic strain of Salmonella enteritidis resulted in a marked induction
      of macrophage activation and HIV production. The stimulatory effect of
      salmonellae was mediated by signals other than lipopolysaccharide. Salmonella
      mutants with specific defects in invasion or intracellular survival were markedly
      less effective in the induction of HIV production. In contrast to S. enteritidis,
      strains of Yersinia enterocolitica, Legionella pneumophila, and Escherichia coli
      did not induce HIV production. However, all of these bacteria induced comparable
      levels of gene expression mediated by the HIV long terminal repeat. The results
      of this study are consistent with the notion that invasive salmonellae possess
      the ability to activate the macrophage by at least one mechanism that is not
      shared with several other species of gram-negative bacteria. Furthermore, the
      expression of this unique property is maximal with Salmonella strains that are
      not only invasive but also capable of prolonged survival within the macrophage.
      Our results indicate that the U1 cell line may be a very useful model system with
      which to examine the biochemical pathways by which internalized salmonellae
      modulate the activation state of the macrophage.

PMID- 7729891
TI  - Adherence of Candida albicans to a cell surface polysaccharide receptor on
      Streptococcus gordonii.
AB  - Candida albicans ATCC 10261 and CA2 bound to cells of the oral bacteria
      Streptococcus gordonii, Streptococcus oralis, and Streptococcus sanguis when
      these bacteria were immobilized onto microtiter plate wells, but they did not
      bind to cells of Streptococcus mutans or Streptococcus salivarius. Cell wall
      polysaccharide was extracted with alkali from S. gordonii NCTC 7869, the
      streptococcal species to which C. albicans bound with highest affinity, and was
      effective in blocking the coaggregation of C. albicans and S. gordonii cells in
      the fluid phase. When fixed to microtiter plate wells, the S. gordonii
      polysaccharide was bound by all strains of C. albicans tested. The polysaccharide
      contained Rha, Glc, GalNAc, GlcNAc, and Gal and was related compositionally to
      previously characterized cell wall polysaccharides from strains of S. oralis and
      S. sanguis. The adherence of yeast cells to the immobilized polysaccharide was
      not inhibitable by a number of saccharides. Antiserum raised to the S. gordonii
      NCTC 7869 polysaccharide blocked adherence of C. albicans ATCC 10261 to the
      polysaccharide. The results identify a complex cell wall polysaccharide of S.
      gordonii as the coaggregation receptor for C. albicans. Adherent interactions of
      yeast cells with streptococci and other bacteria may be important for
      colonization of both hard and soft oral surfaces by C. albicans.

PMID- 7729892
TI  - Internalization of Staphylococcus aureus by endothelial cells induces cytokine
      gene expression.
AB  - The ability of the vascular endothelium to elaborate cytokines in response to
      gram-positive sepsis has received limited attention. This study examined cytokine
      expression by human umbilical vein endothelial cells (EC) following infection
      with a gram-positive bacterial pathogen, Staphylococcus aureus. S. aureus
      infection of EC resulted in the production of interleukin-6 (IL-6) and IL-1 beta.
      For IL-6, message was detected at 3 h after infection, protein was present at 24
      h, and both message and protein persisted for 72 h. IL-1 beta message was
      detected at 12 h, IL-1 beta protein was detected at 24 h, and both persisted for
      72 h. Message for colony-stimulating factor 1 remained unaltered. UV-killed S.
      aureus also elicited IL-1 beta and IL-6 message and protein expression at 24 and
      48 h. Twenty-one clinical isolates of S. aureus were tested, and all induced IL-6
      release by 48 h. However, the laboratory strain 8325-4 did not induce cytokine
      expression at any time point and was internalized by EC 1,000-fold less than
      other strains were. Internalization of latex beads by EC did not induce IL-6 gene
      expression. Furthermore, cytochalasin D treatment of the EC prevented IL-1 and IL
      6 induction by S. aureus but not by tumor necrosis factor alpha or
      lipopolysaccharide. These results indicate that S. aureus is a potent inducer of
      IL-1 and IL-6 in EC and that internalization of S. aureus by EC is necessary for
      their cytokine expression. Thus, our data suggest that the vascular endothelium
      may play an important role in the pathogenesis of septicemia caused by gram
      positive organisms.

PMID- 7729894
TI  - Cellular immune response to Mycobacterium leprae infection in human
      immunodeficiency virus-infected individuals.
AB  - The immune responses to Mycobacterium leprae and other mycobacterial antigens
      were studied in 11 leprosy patients with concurrent human immunodeficiency virus
      type 1 (HIV-1) infection. Three patients manifested borderline lepromatous
      leprosy, and eight patients had borderline tuberculoid (BT) leprosy. Despite the
      low CD4+ T-cell count in the peripheral blood, no histologic or phenotypic change
      in the cellular infiltrate in either the lepromatous or tuberculoid lesions was
      observed when compared with HIV-1-negative patients. Lepromatous lesions
      contained heavily parasitized macrophages and few CD8+ T cells. Lesions from the
      patients with BT leprosy showed extensive CD4+ T-cell infiltration despite a
      significant reduction in CD4+ T-cell counts in the peripheral blood. No acid-fast
      bacilli were detected in the tuberculoid lesions. HIV-1 infection did not alter
      the lack of response in lepromatous leprosy to M. leprae antigens either in vitro
      or in vivo. In contrast, the skin test response to M. leprae antigens as well as
      the in vitro lymphoproliferative responses to mycobacterial antigens that are
      usually seen in patients with tuberculoid leprosy were abrogated in the BT HIV-1+
      patients. However, production of gamma interferon in response to the same stimuli
      was preserved in most of the patients. Analysis of cytokine gene expression
      showed activation of additional cytokine genes in the unstimulated peripheral
      blood cells of patients with both leprosy and HIV-1 infections as compared with
      cells from patients with leprosy alone. These results suggest that granuloma
      formation in leprosy can be independent of the impaired CD4+ T-cell response of
      the HIV-1 infection. Furthermore, in HIV-1+ individuals with M. leprae infection,
      activation of cytokine genes is observed even when the circulating CD4+ T-cell
      count is significantly reduced.

PMID- 7729893
TI  - The rpoS gene from Yersinia enterocolitica and its influence on expression of
      virulence factors.
AB  - The chromosome of Yersinia enterocolitica encodes a heat-stable enterotoxin
      called Yst and a surface antigen called Myf, which closely resembles enterotoxin
      associated fimbriae. Both factors could act in conjunction to produce diarrhea.
      Production of the enterotoxin is regulated by temperature, osmolarity, and pH and
      occurs only when bacteria reach the stationary phase. Myf production is regulated
      by temperature and pH and, as we show in this work, also occurs after the
      exponential growth phase. In an attempt to understand the late-phase expression
      of yst and myf, we cloned, sequenced, and mutagenized the gene encoding RpoS, an
      alternative sigma factor of the RNA polymerase involved in expression of
      stationary-phase genes in other enterobacteria. An intact rpoS gene was necessary
      for full expression of yst in the stationary phase but not for the expression of
      myf and of pYV-encoded virulence determinants.

PMID- 7729895
TI  - Protection of immunocompromised mice against lethal infection with Pseudomonas
      aeruginosa by active or passive immunization with recombinant P. aeruginosa outer
      membrane protein F and outer membrane protein I fusion proteins.
AB  - Recombinant outer membrane proteins (Oprs) of Pseudomonas aeruginosa were
      expressed in Escherichia coli as glutathione S-transferase (GST)-linked fusion
      proteins. GST-linked Oprs F and I (GST-OprF190-350 [GST linked to OprF spanning
      amino acids 190 to 350] and GST-OprI21-83, respectively) and recombinant hybrid
      Oprs (GST-OprF190-342-OprI21-83 and GST-OprI21-83-OprF190-350) were isolated and
      tested for their efficacy as vaccines in immunodeficient mice. GST-OprF-OprI
      protected the mice against a 975-fold 50% lethal dose of P. aeruginosa.
      Expression of GST-unfused OprF-OprI failed in E. coli, although this hybrid
      protein has been expressed without a fusion part in Saccharomyces cerevisiae and
      used for immunizing rabbits. The immune rabbit sera protected severe combined
      deficient (SCID) mice against a 1,000-fold 50% lethal dose of P. aeruginosa.
      Evidence is provided to show that the most C-terminal part of OprF (i.e., amino
      acids 332 to 350) carries an important protective epitope. Opr-based hybrid
      proteins may have implications for a clinical vaccine against P. aeruginosa.

PMID- 7729896
TI  - Endotoxin-induced desensitization of mouse macrophages is mediated in part by
      nitric oxide production.
AB  - Refractoriness (tolerance) to endotoxin effects, such as induction of tumor
      necrosis factor alpha (TNF-alpha) secretion, can be elicited in vitro in
      macrophages by preexposure of cells to endotoxin (lipopolysaccharide [LPS])
      itself. The aim of this study was to determine whether this phenomenon is due to
      negative feedback mediated by the free radical nitric oxide (NO) produced by
      cells when they are activated by LPS. Among several efficient inhibitors of NO
      production, NG-monomethyl-L-arginine did not induce concomitant inhibition of TNF
      alpha secretion. Mouse macrophages that were exposed to LPS in the presence of NG
      monomethyl-L-arginine partially maintained the ability to secrete TNF-alpha in
      response to a second LPS stimulation, compared with cells preexposed to LPS
      alone, thus suggesting that NO is involved in part in LPS-induced desensitization
      of cells. Furthermore, direct exposure of cells to the NO-generating compounds
      sodium nitroprusside and S-nitroso-N-acetylpenicillamine mimicked LPS-induced
      desensitization. However, low concentrations of a synthetic lipid (lipid M4) that
      is structurally analogous to the reducing end of the lipid A moiety of LPS
      induced desensitization of mouse macrophages without concomitant production of
      NO. Taken together, these data suggest that although NO actually takes part in
      LPS-induced desensitization of mouse macrophages, additional and yet unknown
      mechanisms must also exist.

PMID- 7729897
TI  - Intracellular killing of Listeria monocytogenes in the J774.1 macrophage-like
      cell line and the lipopolysaccharide (LPS)-resistant mutant LPS1916 cell line
      defective in the generation of reactive oxygen intermediates after LPS treatment.
AB  - Listeria monocytogenes is a facultative intracellular pathogen and survives
      within phagocytic cells by escaping from phagosomes into the cytoplasm. It has
      been reported that, in vivo, L. monocytogenes is effectively eliminated through
      cell-mediated immunity, especially by macrophages which have been immunologically
      activated by cytokines such as gamma interferon (IFN-gamma). However, this
      killing mechanism for L. monocytogenes and the role of macrophage activation in
      this bacterial killing are unclear. We demonstrated the listericidal effect of
      oxidative radicals induced by lipopolysaccharide (LPS) and IFN-gamma, using a
      macrophage-like cell line, J774.1, and a mutant cell line, LPS1916. LPS1916 cells
      do not exhibit normal generation of O2- and H2O2 after treatment with 0.1
      microgram of LPS per ml, although J774.1 cells generate 100 times the normal
      level of oxidative radicals with the same LPS treatment. The growth of L.
      monocytogenes was strongly inhibited in J774.1 cells pretreated with 0.1
      microgram of LPS per ml or the combination of 0.1 microgram of LPS per ml and 10
      U of IFN-gamma per ml. On the other hand, in LPS1916 cells, the growth of L.
      monocytogenes was not inhibited by treatment with LPS only, although LPS1916
      cells pretreated with the combination of LPS and IFN-gamma showed moderate
      inhibition of listerial growth. This killing was not influenced by treatment with
      NG-monomethyl-L-arginine, which is a strong inhibitor of nitrite oxide
      generation. Interestingly, J774.1 cells treated with LPS did not show enhanced
      intraphagosomal killing of a nonhemolytic strain of avirulent L. monocytogenes
      that lacks the ability to escape from phagosomes, and this killing was not
      influenced by treatment with NG-monomethyl-L-arginine either. These results
      suggest that the reactive oxygen radicals are more important than nitric oxide in
      the mechanism underlying the intracellular killing of virulent L. monocytogenes
      and that there seem to be different killing mechanisms for virulent and avirulent
      strains of L. monocytogenes in activated-macrophage cell lines.

PMID- 7729898
TI  - Expression of Candida albicans SAP1 and SAP2 in experimental vaginitis.
AB  - Several strains of Candida albicans were compared for their ability to cause
      vaginal infection in a rat model, and their vaginopathic potentials were
      correlated with the expression of two aspartyl proteinases genes (SAP1 and SAP2)
      and adherence in vivo to the vaginal epithelium. Dot blot reactions and Northern
      blot analysis with RNA extracted from the vaginal fluid of rats infected with the
      highly vaginopathic strains H12 and 10261 demonstrated the expression of both
      SAP1 and SAP2 during the first week of infection. In contrast, neither gene was
      expressed during infection by a nonvaginopathic strain (N), even though the
      organism could be recovered during the first 24 h postinfection. A moderately
      vaginopathic strain (P) also expressed both genes, but the level of SAP1 mRNA
      appeared to decrease prior to that of SAP2. Neither gene was expressed, even by
      the highly vaginopathic strains, after the first week of infection, concomitant
      with a decrease in the number of organisms recovered from the vaginas. Analysis
      of in vivo adherence showed that the nonvaginopathic strain (N) adhered to
      vaginal epithelial cells less readily than the highly vaginopathic strain (H12)
      and moderately vaginopathic strain (P). Thus, in addition to its inability to
      express SAP1 and SAP2 in vivo, the nonvaginopathic strain does not colonize host
      cells to the same extent as the other strains tested. Our results demonstrate the
      early in vivo expression of two aspartyl proteinase gene during candidal
      vaginitis and suggest its association with the establishment of a vaginal
      infection.

PMID- 7729900
TI  - Variation in the structure of glucuronoxylomannan in isolates from patients with
      recurrent cryptococcal meningitis.
AB  - Capsular glucuronoxylomannans (GXM) of Cryptococcus neoformans var. neoformans
      isolates from patients with recurrent cryptococcal meningitis were analyzed by 1H
      nuclear magnetic resonance spectroscopy and for reactivity with factor sera
      (Iatron, Tokyo, Japan). For each patient the initial and relapse isolates had
      previously been shown to be indistinguishable by DNA restriction fragment length
      polymorphism analysis. For patients J11 and J22 the GXM of the initial and
      relapse isolates were identical. For patients SB4 and SB6 the GXM of the initial
      and relapse isolates differed in structure and reactivity with factor sera. In
      patient SB4 the initial isolate had a serotype A/D structure, and the first
      relapse isolate had a serotype A structure. The second relapse isolate was a
      mixture of structures composed of serotype D components, glucuronomannan (GM),
      and a minor serotype A component. Analysis of the initial isolate from patient
      SB6 showed a structure composed mainly of serotype D, GM, and minor serotype A
      components and components not assigned to a particular serotype (N). The relapse
      isolate had the same composition as the initial isolate except for an increase in
      the serotype A component. This increase in the serotype A component of the
      relapse isolate resulted in a change in the serological specificity from serotype
      D to serotype A/D. The initial isolate from patient J9 had serotype D and GM
      structures. The first two relapse isolates had serotype D, N, and GM structures
      and a minor serotype A component. The third relapse isolate had mainly a serotype
      D structure. All the J9 isolates reacted only with serotype D-specific factor
      serum. These results indicate that some isolates obtained from patients with
      recurrent C. neoformans infections have undergone a change in GXM structure
      during the course of infection. The modification of GXM structure observed in
      some relapse isolates is reflected in changed serological properties. The results
      may have important implications for the design of vaccines and antibody-based
      therapeutic strategies against C. neoformans.

PMID- 7729899
TI  - Actinobacillus actinomycetemcomitans Y4 capsular-polysaccharide-like
      polysaccharide promotes osteoclast-like cell formation by interleukin-1 alpha
      production in mouse marrow cultures.
AB  - The mechanism of osteoclast-like cell formation induced by periodontopathic
      bacterium Actinobacillus actinomycetemcomitans Y4 (serotype b) capsular
      polysaccharide-like polysaccharide (capsular-like polysaccharide) was examined in
      a mouse bone marrow culture system. When mouse bone marrow cells were cultured
      with A. actinomycetemcomitans Y4 capsular-like polysaccharide for 9 days, many
      multinucleated cells were formed. The multinucleated cells showed several
      characteristics of osteoclasts, including tartrate-resistant acid phosphatase
      (TRACP) and the ability to resorb the calcified dentine. In this study, we
      examined the effects of antisera to interleukins on the formation of osteoclast
      like cells induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide.
      Monospecific anti-mouse recombinant interleukin-1 alpha (rIL-1 alpha) serum
      completely inhibited the formation of osteoclast-like cells in the presence of A.
      actinomycetemcomitans Y4 capsular-like polysaccharide. However, anti-mouse rIL-1
      beta and anti-mouse rIL-6 sera showed no effect on osteoclast-like cell
      formation. IL-1 receptor antagonist significantly inhibited the osteoclast-like
      cell formation mediated by A. actinomycetemcomitans Y4 capsular-like
      polysaccharide in mouse marrow cultures. The bioactive IL-1 was detected in the
      culture media of mouse bone marrow cells stimulated with A. actinomycetemcomitans
      Y4 capsular-like polysaccharide. These results indicate that IL-1 alpha is
      involved in the mechanism of the formation of osteoclast-like cells induced by A.
      actinomycetemcomitans Y4 capsular-like polysaccharide. We sought to determine
      whether osteoclast-like cell formation induced by A. actinomycetemcomitans Y4
      capsular-like polysaccharide could be modulated by the protein kinase inhibitors
      H8 and HA1004. The formation of osteoclast-like cells was suppressed by H8 and
      HA1004. These findings suggest that the signals by protein kinases may regulate
      osteoclast-like cell formation induced by A. actinomycetemcomitans Y4 capsular
      like polysaccharide. Furthermore, a correlation between IL-1 alpha and
      prostaglandin E2 in the osteoclast recruitment induced by A.
      actinomycetemcomitans Y4 capsular-like polysaccharide is discussed.

PMID- 7729901
TI  - Human immunoglobulin M paraproteins cross-reactive with Neisseria meningitidis
      group B polysaccharide and fetal brain.
AB  - Three hundred fifty-nine serum samples from patients with immunoglobulin M (IgM)
      or IgG monoclonal gammopathies were tested for binding to the capsular
      polysaccharide (PS) of Neisseria meningitidis group B (MenB PS, poly-alpha[2-->8]
      N-acetylneuraminic acid). Of 159 IgM paraproteins, 7 (4.4%) were positive,
      compared with 0 of 200 IgG paraproteins (P < 0.05). Since MenB PS reactivity was
      limited to the IgM paraproteins, the 159 IgM paraproteins were tested by enzyme
      linked immunosorbent assay (ELISA) for reactivity with seven other bacterial PSs.
      None reacted with meningococcal A or C, Haemophilus influenzae type b, or
      Streptococcus pneumoniae type 3, 6, 14, or 23 PS. The specificity of the MenB PS
      reactive antibodies was confirmed by demonstration of binding to N. meningitidis
      group B cells but not to a capsular PS-deficient mutant and by specific
      inhibition of binding to solid-phase MenB PS by soluble MenB PS in an ELISA. Five
      of five antibodies tested protected infant rats from bacteremia caused by
      Escherichia coli K1, an organism with a PS capsule that also is composed of poly
      alpha[2-->8]-N-acetylneuraminic acid. Each of the seven MenB PS-reactive
      paraproteins had autoantibody activity as defined by binding to homogenates of
      calf brain in a radioimmunoassay. For six of the seven antibodies, binding to
      calf brain was inhibited by the addition of soluble MenB PS. Thus, approximately
      4% of human IgM paraproteins have autoantibody activity to poly-alpha[2-->8]-N
      acetylneuraminic acid, an antigen expressed in fetal brain and cross-reactive
      with the MenB capsular PS. The reason for this skewing of the IgM paraprotein
      repertoire toward reactivity with poly-alpha[2-->8]-N-acetylneuraminic acid
      antigenic determinants is unknown.

PMID- 7729902
TI  - Cloning, expression, and nucleotide sequence of a Staphylococcus aureus gene
      (fbpA) encoding a fibrinogen-binding protein.
AB  - Septicemia due to Staphylococcus aureus often begins as a focal infection (e.g.,
      colonized wounds or catheters) from which the organism gains access to the
      bloodstream. On the basis of recent data from this laboratory, it is likely that
      S. aureus colonizes catheters and endothelium by using a fibrinogen-binding
      protein to mediate adhesion to fibrinogen-coated surfaces. To characterize the
      fibrinogen-reactive protein, we screened a lambda Zap library of S. aureus DB, a
      clinical isolate, for clones that were reactive with fibrinogen. Of 100,000
      plaques screened, 3 were found to react with fibrinogen on immunoblots. Plasmid
      DNA prepared from clones 14, 30, and 36, upon digestion with EcoR1, which
      released the insert, revealed fragments of 4.6, 3.6, and 3.2 kb, respectively. To
      identify the cloned protein expressed in E. coli, cells were fractionated into
      periplasmic, membrane, and cytoplasmic fractions. Expression studies of clone 14,
      which comprised approximately two-thirds of the mature molecule, including the C
      terminus, revealed a 34-kDa fibrinogen-reactive protein in both the periplasmic
      and membrane fractions. This protein, designated FbpA, could be partially
      purified on a fibrinogen column. By using both clones 14 and 36 as templates, the
      complete DNA sequence of the fibrinogen-binding protein was obtained, yielding a
      molecule with a predicted size of 69,991 Da. Although sequence analysis revealed
      a high degree of homology with coagulase, there is a unique sequence of 11 amino
      acids that is not found in three known coagulases as well as two recently cloned
      fibrinogen-binding proteins. This unique sequence shares homology with a cell
      wall anchor motif found in other gram-positive surface proteins.

PMID- 7729903
TI  - Human macrophages acquire a hyporesponsive state of tumor necrosis factor alpha
      production in response to successive Mycobacterium avium serovar 4 stimulation.
AB  - Human macrophages (M phi) from most donors respond to inoculation with
      Mycobacterium avium serovar 4 (M. avium) by tumor necrosis factor alpha (TNF
      alpha) production, which is of critical importance for proper defense against
      microorganisms. An initial infection of M phi with M. avium results in an
      incapacity to accumulate TNF-alpha mRNA after reinfection with M. avium,
      indicating adaptation to a hyporesponsive state by preexposure of the cells to M.
      avium. Adaptation to stimulation with M. avium is abrogated by the cyclooxygenase
      inhibitor indomethacin. In the presence of prostaglandin E2, indomethacin
      exposed, M. avium-treated M phi remain unresponsive to a subsequent M. avium
      stimulus to increase steady-state TNF-alpha mRNA, suggesting that prostaglandin
      E2 is instrumental for the adaptation to an M. avium challenge. TNF-alpha mRNA
      accumulation induced by a second M. avium stimulus in the presence of
      indomethacin is blocked by the protein tyrosine kinase inhibitor herbimycin. In
      contrast, the initial M phi response to M. avium is inhibited by staurosporin, an
      inhibitor of phospholipid Ca(2+)-dependent protein kinases, indicating that the
      initial and the successive TNF-alpha responses to M. avium are dependent on
      different mechanisms.

PMID- 7729904
TI  - Use of porcine fibrinogen as a model glycoprotein to study the binding
      specificity of the three variants of K88 lectin.
AB  - Known glycoproteins were used to determine the differences occurring in the
      binding specificities of the three variants of the K88 lectin in an approach
      essentially based on lectin blotting. During the screening, it was demonstrated
      that each variant of the K88 lectin biotinylated via its amino groups (NbioK88)
      exhibited a characteristic binding to the three chains of porcine fibrinogen.
      NbioK88ab weakly bound to A alpha chains, NbioK88ac bound to B beta and gamma
      chains, and NbioK88ad bound only to the gamma chain. To validate this model, the
      oligosaccharide moieties of porcine fibrinogen were analyzed with glycosidases
      and by lectin blotting and sugar composition. Both the B beta chain and gamma
      chain carry biantennary N-glycans of the N-acetyllactosamine type that are not
      recognized by K88 lectins. A alpha chains are substituted by sialylated T
      antigen. O-glycans were also detected on B beta and gamma chains of porcine
      fibrinogen and contribute to the recognition of these chains by K88ac and K88ad
      fimbriae.

PMID- 7729905
TI  - Identification and characterization of a surface-exposed, 66-kilodalton protein
      from Borrelia burgdorferi.
AB  - The surface-exposed antigens of Borrelia burgdorferi represent important targets
      for the development of a protective immune response. We have identified a
      proteinase K-accessible, 66-kDa protein from B. burgdorferi and have demonstrated
      that at least a portion of this protein is surface exposed. The 66-kDa protein
      was purified by sequential extraction of spirochetes with butanol and Triton X
      114 followed by preparative gel electrophoresis. Polyclonal antibodies developed
      against the purified 66-kDa protein were Borrelia spp. specific, whereas a
      monoclonal antibody, Route 66, displayed a genospecies-specific pattern of
      recognition for the 66-kDa protein. N-terminal amino acid sequence was obtained
      from an internal fragment, a truncated version, and the full-length form of the
      66-kDa protein. A search of protein and gene databases for homologous sequences
      yielded a match with the predicted amino acid sequence from a segment of B.
      burgdorferi chromosomal DNA (P. A. Rosa, D. Hogan, and T. G. Schwan, J. Clin.
      Microbiol. 29:524-532, 1991). The construction of primers based on this DNA
      sequence and the N-terminal amino acid sequence allowed the amplification and
      cloning of the 66-kDa-protein gene. The identity of the cloned gene was verified
      by the recognition of the expressed gene product by Route 66. Pulsed-field gel
      electrophoresis and Southern blot analysis were performed to confirm the
      chromosomal location of the 66-kDa-protein gene. This study describes the
      identification and cloning of the first chromosomally encoded, surface-exposed
      protein from B. burgdoferi.

PMID- 7729906
TI  - Active release of bound antibody by Streptococcus mutans.
AB  - Previous studies have shown that Streptococcus mutants is capable of releasing
      many surface protein antigens, particularly antigen P1. Antigen P1 is
      immunodominant and has been implicated in adherence of S. mutants to the acquired
      pellicles. The purpose of this study is to investigate the significance of
      release of this antigen by the cells. S. mutants NG8 (serotype c) was incubated
      with an anti-P1 rabbit immunoglobulin G (IgG) or a human colostral IgA which
      contains natural anti-P1 activity. Results indicated that the bound antibodies
      were released by the cells in a pH- and time-dependent manner. The optimal pH for
      release was between 6 and 8, and the release rate reached a plateau in 1 h at 37
      degrees C. The release of bound antibodies was considered an active process,
      since heat-killed cells remained capable of antibody binding but failed to
      release the antibodies. The release was also dependent on the age of the culture,
      with early-exponential-phase cells releasing the maximum amount of bound IgG. The
      released IgG was isolated by polyethylene glycol precipitation and protein A
      Sepharose column chromatography and found to be associated with antigen P1,
      indicating that the antibodies were released together with the antigen in the
      form of immune complexes. The binding of S. mutans by secretory IgA (SIgA)
      inhibited the adherence of the cells to salivary agglutinin-coated
      hydroxylapatite. However, when the SIgA-coated S. mutans was allowed to release
      the bound antibodies, the inhibitory effect of SIgA on adherence was abrogated.
      These results suggest that S. mutans is capable of shedding surface-bound
      antibodies in the form of antibody-antigen immune complexes. Such an action may
      be a strategy employed by the cells to counter the neutralizing effect of
      naturally occurring antibodies in the oral cavity.

PMID- 7729907
TI  - Antibody and cytokine responses in a mouse pulmonary model of Shigella flexneri
      serotype 2a infection.
AB  - A murine pulmonary model was used to study the mucosal immune response to
      Shigella flexneri serotype 2a infection. Inoculation of BALB/cJ mice with
      shigellae via the intranasal route resulted in bacterial invasion of bronchial
      and alveolar epithelia with concomitant development of acute suppurative
      bronchiolitis and subsequent development of lethal pneumonia. The pathology of
      pulmonary lesions resembled the colitis that characterizes shigellosis in humans
      and primates. Significant protection against a lethal dose of S. flexneri 2a was
      observed in mice previously infected with two sublethal doses of the homologous
      strain. Immunity against lethal challenge was associated with decreased bacterial
      invasion of the mucosal epithelium. Over the course of two sublethal challenges,
      which constituted primary and secondary immunizations, mice developed pulmonary
      and serum immunoglobulin G and A antibody recognizing both lipopolysaccharide and
      invasion plasmid antigens IpaB and IpaC. Immune mice and naive control mice
      differed in lung lavage cytokine levels following lethal challenge. Immune mice
      developed significantly elevated levels of pulmonary gamma interferon within 6 h
      of challenge, while naive control mice developed elevated levels of this cytokine
      later during the initial 24-h period. Both groups had elevated levels of gamma
      interferon during the 24- to 48-h period of infection. Both groups also had
      elevated levels of tumor necrosis factor alpha within 6 h of challenge, but the
      control mice had significantly higher levels at the 48- and 72-h time points.
      Elevated levels of interleukin-4 were observed only in immunized mice. This
      cytokine appeared within 24 h and receded between 48 and 72 h. Fluorescence
      activated cell sorter analysis of lung parenchymal cells showed that both groups
      experienced an initial influx of monocytes, but the proportion of this cell type
      began to recede in immunized mice after 48 h of infection, while peak levels were
      maintained in the control animals. These studies suggest that elements of local B
      lymphocyte activity, as well as Th1 and Th2 lymphocyte activity, may contribute
      to the survival of immune mice after intranasal challenge with shigellae.

PMID- 7729908
TI  - Lipoarabinomannans derived from different strains of Mycobacterium tuberculosis
      differentially stimulate the activation of NF-kappa B and KBF1 in murine
      macrophages.
AB  - The inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) is rapidly
      induced in macrophages after exposure to Mycobacterium tuberculosis. Recently it
      was shown that lipoarabinomannan (LAM) derived from an attenuated (H37Ra) strain
      of M. tuberculosis (AraLAM) was capable of macrophage activation and induction of
      TNF-alpha production, whereas LAM derived from the virulent Erdman strain
      (ManLAM) was considerably reduced in this activity. A critical component in the
      regulation of many genes central to immune function is the transcription factor
      NF-kappa B. Lipopolysaccharide (LPS)-mediated induction of TNF-alpha expression
      in murine macrophages has been demonstrated to be regulated in part by NF-kappa
      B. In this study, we demonstrate that AraLAM is capable of rapid activation of NF
      kappa B- and KBF1-binding activities in C3H/HeN bone marrow-derived macrophages
      and the J774.A and RAW264.7 murine macrophagelike cell lines, whereas ManLAM is
      considerably less potent at stimulating NF-kappa B. Treatment of RAW264.7 cells
      with AraLAM or LPS results in the stimulation of DNA binding of both forms within
      7.5 min, which peaks within 30 min and 1 h, respectively. Interestingly,
      treatment of RAW264.7 macrophage-like cells with AraLAM, LPS, or ManLAM for
      greater than 2 h resulted in significant accumulation of KBF1. Inhibition of
      protein synthesis blocked the transient nature of NF-kappa B activation as well
      as the accumulation of KBF1. Using Western immunodetection of the NF kappa B1 p50
      subunit, we also show that AraLAM and LPS stimulate the loss of the NF kappa B1
      p105 precursor. These results demonstrate that NF-kappa B and KBF1 are rapidly
      induced in response to AraLAM and may play a role in avirulent M. tuberculosis
      activation of TNF-alpha expression in macrophages. The differential temporal
      regulation of kappa B element DNA-binding activities and the transient
      stimulation of NF kappa B followed by the sustained accumulation of KBF1 may
      serve as a feedback switch ensuring transient induction of TNF-alpha
      transcription.

PMID- 7729909
TI  - Effect of defined point mutations in the pneumolysin gene on the virulence of
      Streptococcus pneumoniae.
AB  - The thiol-activated toxin pneumolysin is a known pneumococcal virulence factor,
      with both cytotoxic (hemolytic) and complement activation properties. Copies of
      the pneumolysin gene carrying defined point mutations affecting either or both of
      these properties were introduced into the chromosome of Streptococcus pneumoniae
      D39 by insertion-duplication mutagenesis. The virulences of these otherwise
      isogenic strains were then compared. There was no significant difference in
      either the median survival time or overall survival rate between mice challenged
      with D39 derivatives producing the wild-type toxin and those expressing a
      pneumolysin gene with an Asp-385-->Asn mutation, which abolishes the complement
      activation property. However, mice challenged with strains carrying either His
      367-->Arg or Trp-433-->Phe plus Cys-428-->Gly mutations, which reduce hemolytic
      activity to approximately 0.02 and 0.0001% of the wild-type level, respectively,
      had significantly greater median survival times and overall survival rates than
      mice challenged with D39 derivatives expressing a wild-type pneumolysin gene. No
      additional reduction in virulence was observed when mice were challenged with a
      D39 derivative carrying Trp-433-->Phe, Cys-428-->Gly, and Asp-385-->Asn, rather
      than Trp-433-->Phe and Cys-428-->Gly, mutations in the pneumolysin gene. Thus, it
      appears that in the intraperitoneal challenge model, the contribution of
      pneumolysin to virulence is largely attributable to its hemolytic (cytotoxic)
      properties rather than to its capacity to activate complement. Interestingly,
      however, the amount of pneumolysin required for full virulence may be very small,
      as D39 derivatives carrying the Trp-433-->Phe mutation (which reduces hemolytic
      activity to 0.1% of the wild-type level) had intermediate virulence.

PMID- 7729910
TI  - Discrimination of virulent and avirulent Streptococcus suis capsular type 2
      isolates from different geographical origins.
AB  - In an effort to relate the protein profile to virulence, proteins from the
      cellular fractions and from culture supernatants of Streptococcus suis capsular
      type 2 strains from different geographical origins were compared by using Western
      blots (immunoblots). The protein profiles of the cellular fractions were similar
      for the majority of virulent and avirulent isolates studied, with the exception
      of three virulent Canadian strains for which a 135-kDa protein was not detected.
      Examination of the culture supernatants revealed the presence of a 135-kDa
      protein in all strains except the same three virulent Canadian isolates. In
      addition, a 110-kDa protein was present in 14 of 16 virulent strains and not in
      avirulent isolates. When injected into mice, the 110-kDa protein induced an
      immunoglobulin G response and protected against infection with homologous and
      heterologous virulent strains. Four strains (1330, 0891, TD10, and R75/S2) that
      were avirulent in the mouse model of infection and four other strains (1591, 999,
      JL590, and AAH4) that were virulent in the mouse model were injected into pigs.
      All virulent strains reproduced the disease, and all avirulent strains failed to
      reproduce the disease (with the exception of transient lameness in one case and
      fever in another case). The 110-kDa protein therefore appears to be a reliable
      virulence marker and a good candidate for a subunit vaccine.

PMID- 7729911
TI  - Antigens derived from lung-stage larvae of Schistosoma mansoni are efficient
      stimulators of proliferation and gamma interferon secretion by lymphocytes from
      mice vaccinated with attenuated larvae.
AB  - Protective immunity in C57BL/6 mice exposed to optimally irradiated larvae of
      Schistosoma mansoni operates against challenge parasites in the lungs and is
      dependent upon T-helper 1 (Th1) lymphocytes which secrete abundant gamma
      interferon (IFN-gamma). As an initial step in the identification of the molecules
      which mediate this immunity, antigenic materials released by larvae at various
      times during in vitro culture were compared for the ability to induce
      proliferation of lymph node cells recovered from mice 4 to 6 days after exposure
      to attenuated parasites. Cells from mice vaccinated with cercariae proliferated
      most strongly to larval antigens released soon after transformation. In contrast,
      cells from mice immunized with lung-stage schistosomula responded poorly to these
      early secretions but proliferated vigorously to antigens released by older
      larvae. In further studies on the cytokine profile of the responding lymphocytes,
      it was observed that the balance between IFN-gamma and interleukin-4 (IL-4)
      secretion depended on the source of antigen used for restimulation. Thus,
      material released between days 6 and 8 by in vitro-cultured larvae, and the
      soluble extracts of whole lung-stage larvae, induced abundant IFN-gamma but
      little IL-4. This finding implies that an overwhelming proportion of the
      lymphocytes responsive to lung-stage antigens had the Th1 phenotype. In contrast,
      antigens from cercariae and skin-stage larvae induced the lowest levels of IFN
      gamma but higher levels of IL-4. It appears that a proportion of the cells with
      specificities for early antigens had the Th2 or Th0 phenotype. Our results
      emphasize that antigens from lung-stage larvae are an important source of
      potentially protective molecules.

PMID- 7729912
TI  - Purification and characterization of a cell-associated hemagglutinin of Vibrio
      parahaemolyticus.
AB  - We found a positive correlation between cell-associated mannose-sensitive
      hemagglutination and adherence of Vibrio parahaemolyticus to rabbit enterocytes
      by investigating 35 strains of V. parahaemolyticus for cell-associated
      hemagglutinin (cHA) and for the ability to adhere to the enterocytes. We purified
      a mannose-sensitive cHA from a Kanagawa phenomenon-positive clinical strain of V.
      parahaemolyticus that exhibited a high level of mannose-sensitive
      hemagglutination and strongly adhered to the enterocytes. The purified cHA is a
      heat-labile, tetrameric protein consisting of four identical subunits of
      approximately 26 kDa each. The adherence to rabbit enterocytes was inhibited in a
      dose-dependent manner by pretreatment of the bacterial cells with D-mannose and
      with the Fab fraction of immunoglobulin G against the purified cHA. Furthermore,
      pretreatment of the enterocytes with the purified cHA inhibited the adherence of
      V. parahaemolyticus. Immunogold electron microscopy revealed that the cHA is
      located on the bacterial cell surface and is not associated with pili. These
      results suggest that cHA is involved in the adherence mechanisms of V.
      parahaemolyticus to the enterocytes and that the receptors for cHA on the
      enterocyte appear to be a D-mannose-containing compound.

PMID- 7729913
TI  - Evidence implicating phospholipase as a virulence factor of Candida albicans.
AB  - Three different approaches were used to investigate the role of extracellular
      phospholipases in the pathogenicity of Candida albicans. First, we compared 11
      blood isolates of this yeast with an equal number of commensal strains isolated
      from the oral cavities of healthy volunteers. Blood isolates produced
      significantly more extracellular phospholipase activity than the commensal
      strains did. Second, two clinical isolates of C. albicans that differed in their
      levels of virulence in a newborn mouse model were compared for their ability to
      secrete phospholipases. The invasive strain produced significantly more
      extracellular phospholipase activity than the noninvasive strain did. Third, nine
      blood isolates were characterized for their phospholipase and proteinase
      production, germ tube formation, growth, and adherence to and damage of
      endothelial cells in vitro. These factors were analyzed subsequently to determine
      whether they predicted mortality in a mouse model of hematogenously disseminated
      candidiasis. By proportional hazard analysis, the relative risk of death was 5.6
      fold higher (95% confidence interval, 1.672 to 18.84 [P < 0.005]) in the mice
      infected with the higher-phospholipase-secreting strains than in the low
      phospholipase secretors. None of the other putative virulence factors predicted
      mortality. Characterization of phospholipases secreted by three of the blood
      isolates showed that these strains secreted both phospholipase B and
      lysophospholipase-transacylase activities. These results implicate extracellular
      phospholipase as a virulence factor in the pathogenesis of hematogenous
      infections caused by C. albicans.

PMID- 7729914
TI  - Dependence of vascular permeability enhancement on cysteine proteinases in
      vesicles of Porphyromonas gingivalis.
AB  - Infection with Porphyromonas gingivalis is strongly associated with adult
      periodontitis, and proteinases are considered to be important virulent factors of
      the bacterium. In order to investigate the function of proteinases in disease
      development we examined vesicles, a biological carrier of these enzymes, for the
      generation of vascular permeability enhancement (VPE) activity, believed to
      correlate with the exudation of gingival crevicular fluid. The vesicles generated
      VPE activity from human plasma in a dose-dependent manner which could be
      inhibited 90% by antipain, a specific inhibitor of the Arg-specific cysteine
      proteinases (Arg-gingipains [RGPs] from P. gingivalis. Incubation of vesicles
      with high-molecular-weight-kininogen (HMWK)-deficient plasma did not result in
      VPE activity. On this basis, RGPs associated with vesicles were assumed to be
      responsible for most of the VPE activity generation via plasma prekallikrein
      activation and subsequent bradykinin production. The secondary pathway for VPE
      activity production was dependent on the direct release of bradykinin from HMWK
      by the concerted action of RGP and a Lys-specific cysteine proteinase (Lys
      gingipain [KGP]), also associated with vesicles. These results indicate that RGP
      and KGP are biologically important VPE factors acting either via prekallikrein
      activation (RGP) and/or HMWK cleavage (RGP and KGP) to release BK and, thereby,
      contributing to the production of gingival crevicular fluid at periodontal sites
      infected with P. gingivalis.

PMID- 7729916
TI  - Inducible immunity with a pilus preparation booster vaccination in an animal
      model of Haemophilus ducreyi infection and disease.
AB  - Using the temperature-dependent rabbit model of Haemophilus ducreyi infection as
      a quantitative virulence assay, we tested the abilities of two bacterial antigen
      preparations to induce protection against subsequent infection and disease.
      Lipooligosaccharide (LOS) and a pilus preparation were purified from H. ducreyi
      35000 and were used in a booster immunization procedure. The serologic response
      to each immunogen was monitored by enzyme immunoassay. H. ducreyi virulence was
      assayed by intraepithelial inoculation and subsequent measurement of disease for
      homologous strain 35000 or clinical isolate RO-34. LOS and the pilus preparation
      induced humoral responses. The kinetics of the LOS antibody response suggest a
      type 1 T-independent response, whereas the pilus preparation induced an
      anamnestic response. An inoculum of 10(5) CFU of H. ducreyi 35000 or RO-34
      consistently produced ulcerative chancroidal lesions in naive rabbit controls.
      Immunization with LOS did not modify the virulence of H. ducreyi 35000.
      Immunization with the strain 35000 pilus preparation significantly reduced the
      severity of disease and the duration of infection and disease compared with
      controls, with either homologous or heterologous strain infection. The histology
      of lesions from pilus preparation-vaccinated rabbits compared with that of
      lesions from controls revealed accelerated lymphoid cell recruitment, more
      prominent plasma cell infiltrate, and reduction in subsequent histiocytic
      infiltration. We conclude that both LOS and the pilus preparation are immunogenic
      and that the latter induces homologous and heterologous strain protection in this
      animal model of infection and disease.

PMID- 7729915
TI  - Oral immunization with recombinant Salmonella typhimurium expressing surface
      protein antigen A of Streptococcus sobrinus: dose response and induction of
      protective humoral responses in rats.
AB  - An attenuated, recombinant Salmonella typhimurium mutant, chi 4072(pYA2905),
      expressing the surface protein antigen A (SpaA) of Streptococcus sobrinus was
      investigated for its effectiveness in inducing protective immune responses
      against S. sobrinus-induced dental caries in an experimental caries model.
      Fischer rats were orally immunized with either 10(8) or 10(9) CFU of S.
      typhimurium chi 4072(pYA2905). Persistence of salmonellae in Peyer's patches and
      spleens and the induction of immune responses were determined. Maximum numbers of
      salmonellae were recovered from Peyer's patches of rats within the first week of
      immunization, with higher numbers recovered from rats given 10(9) CFU than from
      those given 10(8) CFU. Serum anti-Salmonella and anti-SpaA responses increased
      more rapidly in rats given 10(9) CFU than in rats given 10(8) CFU. The salivary
      antibody response to SpaA increased with time, but the response varied in the two
      groups. In a separate study, rats were orally immunized with the recombinant
      Salmonella mutant and then challenged with cariogenic S. sobrinus 6715. The
      levels of serum and salivary antibody and caries activity were assessed at the
      termination of the experiment. Higher levels of salivary immunoglobulin A
      antibody to SpaA and Salmonella carrier were detected in rats given 10(9) CFU
      than in those given 10(8) CFU, and these responses were higher than those in
      nonimmunized controls. Mandibular molars from immunized rats had lower numbers of
      recoverable streptococci and less extensive carious lesions than those from
      nonimmunized, control rats. These data indicate that oral immunization with an
      attenuated recombinant S. typhimurium expressing SpaA of S. sobrinus induces the
      production of antigen-specific mucosal antibody and confers protection against
      dental caries.

PMID- 7729917
TI  - Adherence properties of an mrkD-negative mutant of Klebsiella pneumoniae.
AB  - The role of the mrkD gene in attachment by a type 3 fimbriate Klebsiella
      pneumoniae strain was further characterized. A clinical isolate, K. pneumoniae
      IA565, was found to contain two copies of the gene encoding the fimbrial subunit,
      mrkA, and one copy of the gene encoding the adhesin subunit, mrkD. One copy of
      mrkA was located on the bacterial chromosome, and the other copy was associated
      with mrkD and located on a plasmid. The plasmid-borne mrk gene cluster was lost
      when K. pneumoniae IA565 was subcultured serially in broth at 44 degrees C. The
      resulting mrkD-negative strain, designated K. pneumoniae IApc35, did not exhibit
      the following adherence characteristics associated with K. pneumoniae possessing
      MrkD-positive fimbriae: agglutination of tannic acid-treated human erythrocytes
      and attachment to trypsinized human buccal cells. However, K. pneumoniae IApc35
      produced type 3 fimbriae that were composed of the characteristic 21.5-kDa major
      fimbrial subunit, were reactive with specific serum, and were visualized
      specifically by immunoelectron microscopy. K. pneumoniae IApc35 retained a copy
      of the mrkA gene on its chromosome. This mrkA-containing gene cluster could be
      complemented by a recombinant plasmid carrying only the mrkD gene, resulting in
      restoration of the K. pneumoniae IA565-like adhesive phenotype and demonstration
      of type 3 filament-associated MrkD subunits by using colloidal gold labeling and
      immunoelectron microscopy. These data indicate that K. pneumoniae may contain
      multiple copies of the mrk genes which may be present simultaneously on both
      plasmid and chromosomal DNAs and which may encode fimbriae with different binding
      specificities.

PMID- 7729918
TI  - Role for circulating lipoproteins in protection from endotoxin toxicity.
AB  - Previous studies have shown that endotoxin (lipopolysaccharide [LPS])-induced
      death can be prevented by preincubating LPS with lipoproteins in vitro or by
      infusing large quantities of lipids into animals prior to LPS administration. In
      the present study we determined whether physiological levels of lipids also
      provide protection. Serum lipid levels were decreased by two different
      mechanisms: administration of 4-aminopyrolo-(3,4-D)pyrimide, which prevents the
      hepatic secretion of lipoproteins, and administration of pharmacological doses of
      estradiol, which increases the number of hepatic low-density lipoprotein
      receptors, leading to increased lipoprotein clearance. In both hypolipidemic
      models, LPS-induced mortality is markedly increased compared with that of
      controls with normal serum lipid levels. In both hypolipidemic models,
      administration of exogenous lipoproteins, which increase levels of serum lipids
      into the physiological range, reduces the increased mortality to levels similar
      to that seen in normal animals. In normal lipidemic animals, 63% of 125I-LPS in
      plasma is associated with lipoproteins, where it would not be capable of
      stimulating cytokine production. In contrast, in hypolipidemic animals, very
      little LPS (12 to 17%) is associated with lipoproteins. Rather, more LPS is in
      the lipoprotein-free plasma compartment, where it could exert biological effects.
      In both hypolipidemic models, LPS produces a greater increase in serum tumor
      necrosis factor levels than it does in controls (three- to fivefold increase),
      and administration of exogenous lipoproteins prevents this increase. Cytokines,
      in particular tumor necrosis factor, are responsible for most of the toxic
      effects of LPS. These data provide evidence that physiological levels of serum
      lipids protect animals from LPS toxicity. Thus, lipoproteins, in addition to
      playing a role in lipid transport, may have protective functions. Moreover, as
      part of the immune response, cytokine-induced increases in serum lipid levels may
      play a role in host defense by decreasing the toxicities of biological and
      chemical agents.

PMID- 7729919
TI  - Listeria monocytogenes p60 supports host cell invasion by and in vivo survival of
      attenuated Salmonella typhimurium.
AB  - The extracellular protein p60 is a major virulence factor of the intracellular
      bacterium Listeria monocytogenes. Its roles in pathogen survival in vivo and host
      cell invasion in vitro were studied. To this end, Salmonella typhimurium SL7207
      was used as carrier for secreted p60-HlyA fusion protein by Escherichia coli HlyB
      and HlyD transport proteins. C57BL/6 mice infected intravenously with this strain
      suffered from increased bacterial numbers in livers and spleens compared with the
      p60-nonexpressing control strain, but only transiently. In vitro experiments
      showed that p60 promotes invasion of recombinant S. typhimurium SL7207 p60 into
      hepatocytes and resting macrophages independent from complement. Moreover, the
      uptake of wild-type L. monocytogenes EGD and L. monocytogenes BUG 8, an
      internalin-deficient strain, into hepatocytes was partially blocked by anti-p60
      antibodies. The impaired invasion of dissociated bacterial chains of L.
      monocytogenes RIII, a p60 expression mutant, into hepatocytes and macrophages was
      partially restored by addition of p60- or p60-HlyA-enriched bacterial
      supernatants. These data suggest that the L. monocytogenes surface-associated
      proteins, p60 and internalin, act in concert to achieve optimal uptake into
      nonprofessional phagocytes and macrophages. Together, these experiments reveal a
      substantial impact of p60 on cell invasion and virulence and thus emphasize the
      importance of the intracellular habitat for survival of L. monocytogenes in the
      host.

PMID- 7729920
TI  - Immunoglobulin subclass distribution and dynamics of Shigella-specific antibody
      responses in serum and stool samples in shigellosis.
AB  - To assess the humoral immunological responses at the subclass level in
      shigellosis, specific antibody responses against Shigella dysenteriae 1
      lipopolysaccharide (LPS), S. flexneri Y LPS, invasion plasmid-coded protein
      antigens (Ipa), and Shiga toxin were analyzed. Antibody responses of 41 patients
      with S. dysenteriae 1 infection (SDIP) and 15 patients with S. flexneri infection
      (SFIP) were compared with those of controls (n = 40). The levels of total
      immunoglobulin G (IgG), IgA, IgM, and albumin in serum and stool samples were
      analyzed. In addition, total IgA (t-IgA), secretory IgA (s-IgA), and antigen
      specific s-IgA in fecal samples were analyzed to evaluate the specificities and
      magnitudes of the mucosal immune responses. By comparing the relative increases
      in optical density for each IgG subclass separately, it was determined that the
      anti-LPS (homologous) response initially increased in the order IgG2 > IgG1 >
      IgG3 > IgG4 and that this order changed to IgG2 > IgG3 > IgG1 > IgG4 later in the
      disease. The IgG subclass response against protein antigens initially showed the
      order IgG1 > IgG3 > IgG2 > IgG4, which changed to IgG3 > IgG1 > IgG2 > IgG4 later
      in the disease. A significant increase in the proportion of IgA2 among t-IgA
      compared with that in controls was seen in both SDIP and SFIP, while significant
      changes in the proportions of IgG1 and IgG2 among t-IgG compared with controls
      was seen only in SDIP. The anti-LPS IgA2 response was more prominent in SDIP than
      in SFIP. We found an early peak of antigen-specific s-IgA in fecal samples, with
      a shorter duration than the corresponding response in serum samples. The
      simultaneous increase of serum IgA, fecal t-IgA, and s-IgA in SDIP compared with
      those in SFIP suggests that there is a massive increase in the local IgA
      production, giving an increase in systemic IgA concomitant with an extensive gut
      mucosal inflammation leading to an increased loss of albumin, IgG, and IgA with a
      high ratio of t-IgA to s-IgA.

PMID- 7729921
TI  - A recombinant Leishmania chagasi antigen that stimulates cellular immune
      responses in infected mice.
AB  - Cellular immune mechanisms resulting in gamma interferon production are critical
      for protection against visceral leishmaniasis. Antigens stimulating T-cell
      responses are likely present in the intracellular amastigote form of the
      parasite, since this is the form found in a mammalian host. To identify T-cell
      antigens of Leishmania chagasi, the parasite causing South American visceral
      leishmaniasis, we used a double antibody-T-cell technique to screen an amastigote
      cDNA library. One cDNA selected (Lcr1) encodes an antigen that stimulated
      proliferation of splenic T lymphocytes from infected mice that were either
      resistant (C3H.HeJ) or susceptible (BALB/c) to L. chagasi infection. The Lcr1
      cDNA contains four highly divergent 201-bp repeats homologous to the 204-bp
      repeat of a Trypanosoma cruzi flagellar antigen gene. Results are consistent with
      a single copy of the Lcr1 gene producing an mRNA of > 10 kb and a protein of >
      200 kDa. Recombinant Lcr1, cloned adjacent to polyhistidine and purified on a
      nickel affinity column, stimulated gamma interferon but not interleukin-4 (IL-4),
      IL-5, or IL-10 secretion by T-cell-enriched splenocytes from either susceptible
      or resistant mice during L. chagasi infection. Immunization with Lcr1 partially
      protected BALB/c mice against challenge with L. chagasi, indicating the utility
      of the double screening approach in selecting relevant T-cell antigens.

PMID- 7729922
TI  - Lack of involvement of nitric oxide in killing of Aspergillus fumigatus conidia
      by pulmonary alveolar macrophages.
AB  - Nitric oxide is an important antimicrobial mechanism of phagocytes from mice and
      rats, but in the case of human phagocytes, secretion is still controversial. We
      investigated whether nitric oxide is involved in the killing of Aspergillus
      fumigatus conidia by human or murine pulmonary alveolar macrophages. Stimulation
      of the macrophages with gamma interferon and Escherichia coli lipopolysaccharide
      had no effect on fungicidal activity against conidia in vitro, with or without
      the addition of tetrahydrobiopterin. Killing of conidia (means +/- standard
      deviations) by murine or human alveolar macrophages, before and after
      stimulation, was 44% +/- 13% and 49% +/- 12% (P = 0.34) and 24% +/- 5% and 29% +/
      10% (P = 0.20), respectively. Fungicidal activity was unaltered in the presence
      of the competitive inhibitor NG-monomethyl L-arginine, and nitrite was
      undetectable in cell supernatants. Peritoneal macrophages from B6C3F1 mice
      produced 18 mumol of nitrite per 10(6) cells in 18 h. In conclusion, nitric oxide
      does not appear to be involved in the fungicidal activity of murine or human
      alveolar macrophages against A. fumigatus conidia.

PMID- 7729923
TI  - Impact of antigen-presenting cells on cytokine profiles of human Th clones
      established after stimulation with Mycobacterium tuberculosis antigens.
AB  - Human T cells reactive with mycobacterial antigens are generally considered to
      correlate with a Th1 cytokine profile. Our data show that, in addition, Th0 and
      Th2 clones develop in bulk culture with appropriate antigen-presenting cells
      before cloning. CD4+ blasts activated by mycobacterial antigens were cloned, and
      their mRNA patterns for the interleukins (IL) IL-2, IL-4, IL-5, IL-6, and IL-10
      and gamma interferon were characterized by reverse-transcribed PCR. Nonadherent,
      nonrosetting, enriched peripheral blood mononuclear cells promoted development of
      Th0; after further depletion of monocytes and natural killer cells, Th2 clones
      were also found. Epstein-Barr virus-transformed B cells, with specificity for the
      stimulating antigen, increased the proportion of Th2 clones.

PMID- 7729924
TI  - Molecular cloning of Proteus mirabilis uroepithelial cell adherence (uca) genes.
AB  - Proteus mirabilis bacteria are a common cause of hospital-acquired urinary tract
      infection. In a previous study, we described a P. mirabilis fimbrial protein,
      UCA, that adhered to human uroepithelial cells. Genes sufficient for expression
      of UCA adherence were cloned into Escherichia coli K-12. E. coli bacteria that
      contained the uca recombinant plasmid adhered to human uroepithelial cells. In
      addition, the ucaA gene encoding the structural component of UCA pili was
      subcloned, and its DNA sequence was determined. Amino acid sequence homology (30
      to 50%) was found between mature UcaA protein and pilins from pathogenic bacteria
      representing several genera, including E. coli F17, G, and type 1C pilins,
      Haemophilus M43 pilin, and a Bordetella pilin.

PMID- 7729925
TI  - The genes for the Clostridium botulinum type G toxin complex are on a plasmid.
AB  - Clostridium botulinum type G produces a toxin complex that is composed of
      neurotoxin, hemagglutinin, and nontoxic nonhemagglutinin. The three genes
      encoding these proteins were closely linked on a plasmid of about 114 kb (76 MDa)
      but not on chromosomal DNA. In contrast to the genes of other C. botulinum
      serotypes, the genes encoding type G toxin are on a plasmid.

PMID- 7729926
TI  - The LBI-method for automated indexing of diagnoses by using SNOMED. Part 2.
      Evaluation.
AB  - We present a simple, formal, lexicon-based method for automated indexing of
      diagnoses based on the Systematized Nomenclature of Medicine (SNOMED), called LBI
      method. Part 1 gave an introduction to the LBI-method and presented its
      realisation as application system SALBIDH. Part 2 presents the design and the
      results of an evaluation study to judge the quality of the LBI-method. In this
      evaluation study the quality of automated indexing as well as the quality of the
      retrieval of patient data by using automated indexed diagnoses was examined. The
      results show that the retrieval based on SNOMED indices is at least as good as
      the retrieval based on ICD classes despite a lot of indexing errors. From this we
      gather that our system is not yet good enough for immediate routine use but that
      an appropriate indexing quality and, as a result, a higher retrieval quality can
      be achieved after few improvements of the LBI-method, especially after revision
      of the lexicons.

PMID- 7729927
TI  - The estimation of event related potentials affected by random shifts and
      scalings.
AB  - There is considerable evidence for trial to trial variability of the event
      related potentials (ERPs) within a given subject's recording. This variability
      influences the outcome of usual procedures in ERP analysis. Better results may be
      obtained if the sources of variability are explicitly taken into account in an
      appropriate model. This paper considers a probabilistic model, the random shift
      and scaling (RSS) model, where the response is modified by a random time shift
      and a random scale factor. In addition to this, an additional random scale factor
      which affects both the response and the background noise is taken into account.
      This time shift and these scale factors are handled as nuisance parameters.
      Maximum likelihood and least squares estimators of these parameters and the
      waveform of response are derived for the RSS model. It is shown that the Woody
      estimate of the ERP reported in earlier work can be derived by restricting the
      assumptions for the RSS model. Test statistics for hypotheses on means are
      obtained for the RSS model and a new type of discriminant function. The
      usefulness of the method is illustrated by means of simulation studies. Receiver
      operating characteristic (ROC) curves are used to demonstrate that the new type
      of discriminant performs better than the usual Fisher's Linear Discriminant.

PMID- 7729928
TI  - Measuring the dissimilarity between EEG recordings through a non-linear dynamical
      system approach.
AB  - A new measure of dissimilarity between two EEG segments is proposed. It is
      derived from the application of the mathematical concept of distance between
      series of one-step predictions according to the estimated non-linear
      autoregressive functions. The non-linear autoregressive estimation is performed
      by non-parametric regression using kernel estimators. The possibility of applying
      this measure for automatic classification of EEG segments is explored. For this
      purpose multidimensional scaling and cluster analyses are applied on the basis of
      the calculated dissimilarity measures. In particular, its application to
      different EEG segments with delta activity and also with alpha waves reveals high
      agreement with visual classification by EEG specialists.

PMID- 7729929
TI  - Bacterial colony counting using distance transform.
AB  - A distance-transform based technique is presented for the segmentation of
      monochrome images of colonies grown on membrane filters. This is used to count
      the number of Escherichia coli in a given water sample, which is used as a
      parameter for determining water quality. The result is compared with fuzzy c
      means clustering approach.

PMID- 7729930
TI  - Particle-fluid suspension model of blood flow through stenotic vessels with
      applications.
AB  - The present study deals with the problem of blood flow through stenotic vessels
      when blood is represented by a particle-fluid suspension model, i.e. a suspension
      of red blood cells in plasma. The expression for the dimensionless resistance to
      flow, the wall shear stress, and the shearing stress on the wall at the maximum
      height of the stenosis are derived. The results obtained in the analysis are
      discussed in brief, both qualitatively and quantitatively by comparison with
      other theories. It is observed that the magnitudes of the blood flow
      characteristics significantly increase with an increase in the red cell
      concentration. The importance of the decreasing vessel diameter is also pointed
      out. Finally, to observe the biological relevance of the analysis, the results
      obtained are used to compute the blood flow characteristics for normal and
      diseased blood using the experimental data from published literature and results
      are compared with those computed using the present theoretical approach.

PMID- 7729931
TI  - Evaluation of a decision support system in a medical environment.
AB  - This paper describes the impact of a decision support system on the quality of
      recorded diagnoses and the completeness of medical records. The assumption is
      that for quality assessment purposes enough data have to be recorded in an
      electronic medical record so that diagnostic decisions can be justified. The
      hypotheses were tested that active decision support will lead to better quality
      recorded diagnoses and more complete medical records. Three groups of ten GPs
      were presented with 10 cases each. The GPs had to enter the data about these
      cases in a GP information system. One group of GPs was not supported. The second
      group was presented with the ICHPPC-II-Defined criteria that had to be fulfilled
      when a diagnosis was entered. In a third group, the GPs were asked those data
      that were needed to justify an entered diagnosis (active support). It could be
      shown that the last group of GPs entered better quality diagnoses than the other
      two groups. These latter groups also entered so little data that most of their
      diagnoses could not be justified. It is concluded from the study that only active
      decision support will lead to better diagnoses and a more complete medical record
      that can be used for quality assessment.

PMID- 7729932
TI  - Development and evaluation of a new automated dispensing system.
AB  - Promptness of medicine preparation is one of the important tasks the pharmacy has
      to tackle. A new automated dispensing system has been developed in order to adopt
      parallel preparation of the prescription. The system consists of a large LAN
      system which is connected to a host-computer, control-computer, automatic
      preparation machines and conveyer lines. The prescription data issued by each
      physician are first audited by the host computer and then used as the date for
      preparation. Prepared data checked by pharmacists are delivered to the manual
      preparation station (tablets, powder, topical drugs, and solutions) as a
      preparation instruction sheet and transmitted directly to the automatic
      preparation machines (e.g. medicine bag printing machines and automatic tablet
      dispensing and packaging machines). In collecting the prepared medicines, a
      controlled conveyer line was established. The waiting time decreased
      significantly after the system was introduced. This system not only reduces
      actual medicine preparation time but also improves the progress of the dispensing
      operation efficiency.

PMID- 7729933
TI  - DIVANU: a new method for global optimization.
AB  - We propose a new method, DIVANU (Diminution of Variables Number), for numerically
      solving minimization problems involving any function of any variables. This
      method uses a reducing transformation. We have used this method for applications
      to biological problems. The identification of models is treated.

PMID- 7729934
TI  - Consultation behaviour of residents supported with a protocol processing system
      (ProtoVIEW) at the emergency ward.
AB  - We evaluated the consultation behaviour of residents using a protocol processing
      system in routine clinical practice. A total of 125 consecutive patients, of age
      16 years or older with an isolated fracture without concomitant lesions, were
      treated with computer support between 13 October 1992 and 9 June 1993. All eight
      surgical residents who worked at the emergency ward of the University Hospital in
      Nijmegen, The Netherlands participated. The mean consultancy time, method of
      information retrieval, number of correct protocols found, number of windows
      retrieved and attitude towards ProtoVIEW as a useful information source were
      estimated. Main results are: a mean consultancy time of 1.5 min per case,
      residents browsed through the protocol information more often than using keyword
      search. The correct protocols were found in 98% of the cases while on average a
      minimum number of text-browse windows was retrieved. Residents were positive
      about the way protocols were presented and about the information supplied by
      ProtoVIEW. From this study we may conclude that ProtoVIEW consultation is hardly
      time consuming, and easy to use. Since keyword search was hardly used, expanding
      the number of synonyms may stimulate searching by keyword more often.

PMID- 7729935
TI  - Maximum a posteriori estimation of change points in the EEG.
AB  - A new approach for EEG segmentation is introduced. This is based on a methodology
      for optimal segmentation of non-stationary signals derived from the maximum a
      posteriori estimation principle. It is a model-based, not sequential approach
      that allows for segmentation at different resolution levels. The features of the
      methodology are illustrated by its application to EEG recordings containing
      several types of spectral changes due to normal and pathological variations of
      spontaneous brain rhythmic activities, as well as physiological artifacts.

PMID- 7729936
TI  - An epidemiological study of posterior uveal melanoma in Israel, 1961-1989.
AB  - Trends in the incidence rate of uveal melanoma in Israel during the period 1961
      1989 among Jews of various geographical origins and among non-Jews were examined,
      and found to be stable over time. Based on data of the Israel Cancer Registry,
      515 cases were included in the final study population after an independent case
      finding ascertainment survey. The average annual incidence rate per million for
      all Jews was 5.7 for both males and females; the rates for non-Jews were: males
      1.6, females 1.3. Incidence rates within the Jewish sub-populations show
      significant differences. The highest rates by sub-population were for Jews born
      in Europe or America (7.5 for males and for females), followed by Jews born in
      Israel (males 6.8, females 6.7); and lowest in Jews born in Africa (males 2.1,
      females 2.3) and Asia (males 1.6, females 2.8). Jews born in Israel had rates
      lower than Jews born in Europe and America during the 1960s, but in the 1980s the
      situation was reversed. Results suggest that rate differences between population
      groups and over time stem from constitutional factors or from the direct or
      indirect effect of sunlight radiation, whether early in life or from cumulative
      exposure.

PMID- 7729937
TI  - Cancer survival in Khon Kaen Province, Thailand.
AB  - Thailand is one of the few developing countries for which population-based cancer
      survival data are available. Using clinical follow-up information and reply-paid
      postal enquiries, 10,333 residents of Khon Kaen province registered with cancer
      in the period 1985-1992 were followed-up to the end of 1993. The sites of the
      most common cancers in the province were liver (5-year relative survival rate
      9.2%), cervix (60.1%), lung (15.4%), breast (48.1%) and large bowel (41.9%).
      Results for Khon Kaen were compared with age-standardized survival data for the
      US and Scotland. Survival was consistently higher for US whites compared to Khon
      Kaen residents for those cancers whose prognosis is associated with early
      diagnosis (breast, cervix and large bowel) or the availability of intensive
      therapy (leukaemia and lymphoma). The main implication of these results for
      cancer control in Thailand is that the interventions of greatest potential
      benefit are those designed to promote early detection. More than one-third of all
      cancers in Thailand are liver tumours: primary prevention through control of
      hepatitis-B infection and liver fluke infestation is the only effective strategy
      for their control.

PMID- 7729938
TI  - Changes in biological markers after primary chemotherapy for breast cancers.
AB  - The profiles of functional (proliferative rate and cell distribution in the cell
      cycle) and phenotypic (nuclear DNA content and hormone receptor status)
      biological markers and the expression of P53 and Bcl-2 proteins were
      prospectively evaluated in breast cancers before and after different regimens of
      primary chemotherapy. Overall, changes induced on the 2 proliferation indices (3H
      thymidine labelling index, 3H-dT LI, and flow-cytometric S-phase fraction, FCM-S)
      mainly consisted of a decrease for rapidly proliferating tumours and an increase
      or no change for slowly proliferating tumours. However, when considered as a
      function of treatment type, changes of 3H-dT LI and FCM-S were superimposable in
      rapidly proliferating tumours, regardless of the type of treatment, and in slowly
      proliferating tumours only after anthracycline-including regimens. Conversely,
      following CMF, FCM-S was increased in 90% of the cases and 3H-dT LI in only 50%.
      Our data imply that the 2 proliferation indices could reflect different
      phenomena: an actual variation of proliferative activity by 3H-dT LI and an
      accumulation of cells in the S-phase by FCM-S. In addition, a higher accumulation
      of cells in G2-M phases could be detected by FCM after anthracycline-including
      regimens than after CMF. The fraction of P53-positive cells was reduced by
      primary chemotherapy in about 50% of P53-positive tumours, whereas Bcl-2
      expression was only marginally affected. DNA ploidy and hormone receptor status
      did not change in about 75% of cases, regardless of the chemotherapeutic regimen.

PMID- 7729939
TI  - The presence of persistent high-risk HPV genotypes in dysplastic cervical lesions
      is associated with progressive disease: natural history up to 36 months.
AB  - To evaluate the clinical significance of HPV genotyping for the prediction of
      progressive cervical intraepithelial neoplasia (CIN) in women with
      cytomorphologically abnormal smears, a prospective, blind, non-intervention study
      was performed. A total of 342 patients screened with cytomorphologically abnormal
      cervical smears were monitored every 3-4 months by cervical cytology, colposcopy
      and HPV testing using PCR. Women with progressive CIN disease were defined as
      patients developing lesions with a colposcopic impression of CIN III over more
      than 2 quadrants or resulting in a cytological smear equivalent to Pap 5. These
      patients were subsequently treated according to standard procedures. If any doubt
      arose about the true status of the patients (n = 75) these patients were censored
      and biopsied. The mean follow-up time was 16.5 months (range 3-36 months).
      Nineteen women showed progressive CIN disease and all appeared to be continuously
      HPV-positive from the start of the study. At biopsy, all these patients were
      histologically classified as CIN III. Seventeen of these women were positive for
      high-risk HPV types. Two cases were classified as still unidentified HPV. No
      progression was seen in the absence of HPV DNA or in the presence of low-risk HPV
      types. In life-table analysis the cumulative rate of progressive, histologically
      verified CIN disease was 17% after 36 months. Further analyses showed that other
      risk factors such as age, sexarche, number of sexual partners or smoking hardly
      influenced the effect of HPV on progression. The results show that the continuous
      presence of high-risk HPV types in women with cytomorphologically abnormal smears
      is a strong marker for progressive CIN disease.

PMID- 7729940
TI  - Human papillomavirus and cervical intraepithelial neoplasia grade II-III: a
      population-based case-control study.
AB  - The association between certain human papillomaviruses (HPV) and cervical
      intraepithelial neoplasia (CIN) is well documented, but there is uncertainty
      about the strength of association and the role of co-factors is unclear. This
      population-based case-control study in Norwegian women 20-44 years of age
      included 103 cases with histologically confirmed CIN II-III and 234 age-matched
      and randomly selected controls. Cytological specimens from the cervix were
      analyzed using the polymerase chain reaction (PCR). In all, 91% of the cases and
      15% of the controls were HPV DNA positive, giving a crude odds ratio (OR) of 67.2
      (95% confidence interval: 28.6-157.5). The association between HPV 16 and CIN II
      III was even stronger (crude OR = 123.9; 46.7 - 328.5). In logistic regression
      analysis, additional to HPV, only a high number of sexual partners and a low
      educational level contributed independently to the risk. The adjusted OR for the
      association between HPV and CIN II-III was 72.8 (95% CI: 27.6-191.9). The
      association between HPV and CIN remains very strong even after adjustment for
      proposed confounding factors. The results therefore support the role of HPV as a
      causative agent in the development of CIN.

PMID- 7729941
TI  - Mutations clustered in exon 5 of the p53 gene in primary nasopharyngeal
      carcinomas from southeastern Asia.
AB  - Mutations in the p53 tumor suppressor gene play an important role in the
      development of many common human malignancies. In nasopharyngeal carcinomas
      (NPC), p53 gene mutations were not detected in primary tumors, with one exception
      for a primary tumor displaying a p53 mutation at codon 280, whereas p53 mutations
      were identified in some metastatic and nude mouse-passaged NPC specimens. In the
      present report, 41 NPC primary tumors of the undifferentiated carcinoma
      nasopharyngeal type (UCNT; 21 from Hong Kong and 20 from Guangxi, southeastern
      China) were studied. Four point mutations that result in amino acid substitutions
      were identified by PCR amplification of exons 2-9 and direct DNA sequencing,
      combined with PCR-single-strand conformation polymorphism analysis. The 4
      mutations detected were clustered within the DNA stretch from codon 175 to 177.
      Our data, taken together with those of others, suggest that mutation in p53 may
      occur in NPC at various points during tumorigenesis. Alternative mechanisms of
      p53 inactivation in NPC are also possible.

PMID- 7729942
TI  - O6-methylguanine-DNA methyltransferase activity in breast and brain tumors.
AB  - The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a main
      determinant of resistance of tumor cells to the cytostatic activity of
      chemotherapeutic alkylating agents (methylating and chloroethylating
      nitrosoureas) and is effective in protecting normal cells against genotoxic and
      carcinogenic effects resulting from DNA alkylation. Therefore, the level of
      expression of MGMT is significance for the response of both the tumor and the non
      target tissue following application of nitrosoureas in tumor therapy. To
      determine the expression of MGMT in tumor tissue, we have assayed MGMT activity
      in 68 breast carcinomas and 38 brain tumors. There was a wide variation of MGMT
      expression in breast carcinomas ranging from below the level of detection up to
      863 fmol/mg protein. About 4% of breast tumors did not display detectable MGMT,
      15% had activity lower than 100 fmol/mg protein, and 26% expressed more than 500
      fmol/mg. The mean level of expression was 321 fmol/mg. In brain tumors
      (astrocytoma WHO grade I, II, and III, and glioblastoma WHO grade IV) the MGMT
      activity was generally lower than in breast tumors, ranging from below the level
      of detection up to 238 fmol/mg. The mean level of expression was 55 fmol/mg. Five
      percent of the brain tumors had no detectable MGMT activity. The MGMT repair
      activity correlated well with the amount of MGMT protein present in tumor
      samples, as shown by Western-blot analysis, indicating that loss of MGMT repair
      activity is due to inability of these tumor cells to synthesize the protein.

PMID- 7729943
TI  - Epstein-Barr virus (EBV) in Malaysian upper-aerodigestive-tract lymphoma:
      incidence and sub-type.
AB  - Epstein-Barr virus (EBV) type B, a less potent transformer of B lymphocytes than
      type A, has rarely been detected in EBV-associated neoplasms except in AIDS
      related lymphomas, in which about 50% of the cases contained this sub-type. In
      this study we analyzed the association of EBV and the distribution of virus sub
      types in Asian non-Hodgkin's lymphoma (NHL) of the upper aerodigestive tract. We
      studied archival material of 29 NHL cases from Malaysia. B- and T-cell associated
      antigens were demonstrated by immunohistochemistry, and EBV early RNA EBER-1 was
      demonstrated using the RNA in situ hybridization technique. EBV was detected in
      the majority of tumour cells in 11/13 T-NHL but in only 1/16 B-NHL. EBV was sub
      typed by single-step polymerase chain reaction of the EBNA-2 gene. This was
      successful in 9/10 cases of EBER-1-positive tumours and all contained type-A
      virus only. Our results showed a preponderance of T-cell lymphoma of the upper
      aerodigestive tract in the ethnic Chinese group of Malaysian patients, and EBV
      was strongly associated with T-NHL but not with B-NHL. Our results suggest that
      type-A EBV is the prevalent sub-type in Asian NHL of the upper aerodigestive
      tract, similarly to findings in Asian nasopharyngeal carcinoma.

PMID- 7729944
TI  - Incidence and prognostic significance of vascular and neural invasion in squamous
      cell carcinomas of the esophagus.
AB  - The prognostic influence of blood-vessel invasion (BVI), lymphatic-vessel
      invasion (LVI) and neural invasion (NI) was evaluated retrospectively in a series
      of 161 patients with squamous cell carcinoma (SCC) of the esophagus who underwent
      esophageal resection. Evidence of BVI, LVI and NI was found in 32.9%, 48.5% and
      26.1%, respectively. Incidence of BVI, LVI and NI was significantly higher in
      high pT categories (pT3 and pT4) than in low pT categories (pT1 and pT2) and in
      patients with distant metastases than in patients without distant metastases.
      Incidence of LVI and NI in lymph-node-positive patients was significantly higher
      than in lymph-node-negative patients. The 5-year survival rate was significantly
      lower in patients with BVI or LVI than in patients without BVI or LVI. Patients
      with evidence of NI showed no significant differences in 5-year survival from
      patients without evidence of NI. By stepwise multivariate Cox regression
      analysis, BVI and LVI were shown to be independent prognostic factors. A search
      for vascular invasion may therefore provide additional prognostic precision in
      SCC of the esophagus.

PMID- 7729945
TI  - HPV infection in cervical-cancer cases in Russia.
AB  - The presence of human papillomavirus (HPV) sequences in 21 biopsies from cervical
      carcinomas, 11 specimens of tissues adjacent to tumours, 2 specimens of cervical
      tissues with radiation fibrosis from patients after radiation therapy of cervical
      cancer and 7 normal epithelial tissues from the patients with other genital
      tumours were examined by polymerase chain reaction (PCR) and Southern-blot
      analysis. All tumours were HPV-positive by type-specific PCR and 86% by Southern
      blot analysis. In normal epithelial and adjacent tissues, HPV sequences were
      detected in 20% of samples by Southern-blot analysis and in 70% of samples by
      PCR, including 2 cases of tissues after radiation therapy. HPV16 was the most
      prevalent type in tumours (18/21) as well as in normal epithelial tissues (5/7).
      One HPV-positive tumour contained HPV18 DNA and 2 were doubly infected with HPVs
      16 and 18 (2/21). The persistence of exclusively episomal HPV16 DNA was observed
      in 5 out of 11 tumours examined: 3 cases of squamous-cell carcinomas on the early
      stage of tumour progression and 2 advanced tumours (squamous-cell carcinoma and
      adenocarcinoma). The integration of HPV16 genome was detected in 6 out of 11
      tumours, but most of them contained episomal forms of viral DNA simultaneously (5
      out of 6). The integrative HPV18 genome was found in 2 tumours examined, and the
      persistence of episomal forms was also observed in one of them. Our data
      demonstrate that cervical tumours are associated invariably with high-risk types
      of HPV in Russia.

PMID- 7729946
TI  - alpha-Interferon potentiates epidermal growth factor receptor-mediated effects on
      human epidermoid carcinoma KB cells.
AB  - The molecular mechanisms underlying the growth inhibition of human tumor cells
      induced by recombinant interferon-alpha (IFN alpha) are mostly unknown. It has
      been proposed that this effect could be related to down-regulation and/or
      impaired function of peptide growth factor receptors (PGF-Rs) in tumor cells
      exposed to IFN alpha. However, we have previously described that IFN alpha
      induced growth inhibition of human epidermoid carcinoma cells is paralleled by up
      regulation of epidermal growth factor receptor (EGF-R). Here we report that an
      increase in EGF-R synthesis is detectable after 3 hr of exposure to cytostatic
      concentration of IFN alpha in epidermoid KB tumor cells. In these experimental
      conditions IFN alpha does not depress and even potentiates EGF-R function. IFN
      alpha-treated KB cells retain sensitivity to the cytotoxic activity of the anti
      EGF-R 225 monoclonal antibody (MAb), which acts through receptor blockade, and
      are sensitized to the growth-promoting effect of EGF. EGF-induced tyrosine (tyr)
      phosphorylation both of total cellular protein extracts and of the
      immunoprecipitated EGF-R is increased in IFN alpha-treated cells. We conclude
      that a cross-talk between IFN alpha and EGF occurs in KB cells since IFN alpha,
      at cytostatic concentration, potentiates the effects mediated by the EGF-R.

PMID- 7729947
TI  - Effects of interferon-alpha on human B cells: repression of apoptosis and
      prevention of cell growth are independent responses of Burkitt lymphoma lines.
AB  - We have previously shown that interferon-alpha (IFN-alpha) can repress apoptosis
      in Burkitt lymphoma (BL) cells. In this study, we have compared this protective
      response with a further, well-established effect of IFN-alpha on BL cells, that
      of growth arrest. Of a panel of BL lines comprising (i) EBV-positive and 
      negative lines that retain the phenotype of the parental tumour cells and (ii)
      the prototype IFN-alpha-growth-inhibited line, Daudi, only Daudi cells were found
      to undergo substantial growth inhibition in response to the cytokine. By
      contrast, all lines, with the notable exception of Daudi, were protected by IFN
      alpha from high-rate apoptosis initiated by the Ca2+ ionophore ionomycin.
      Ionomycin failed to elicit an IFN-alpha-repressible apoptotic response in either
      wild-type Daudi cells or IFN-resistant sublines that were refractory to the
      growth-arresting effects of the cytokine. Analysis of c-myc protein levels
      confirmed previous observations that repression of apoptosis in IFN-alpha
      rescuable BL cells was associated with an early inhibition of myc that was
      followed by a return to high-level expression. Significantly, ionomycin alone
      induced a comparable transient inhibition of myc protein in Daudi cells. In Daudi
      cells, but not in IFN-alpha-rescuable BL cells, renewed expression of myc
      observed after the early, transient down-regulation was followed by sustained
      down-regulation of the protein, which paralleled growth arrest. Our results
      indicate that long-term growth arrest and repression of apoptosis in BL are
      distinct cellular responses to IFN-alpha.

PMID- 7729948
TI  - Role of anti-LFA-1 and anti-ICAM-1 combined MAb treatment in the rejection of
      tumors induced by Moloney murine sarcoma virus (M-MSV).
AB  - We investigated the effect of combined treatment with anti-LFA-1 and anti-ICAM-1
      monoclonal antibodies (MAbs) in the immune reaction to Moloney-murine-sarcoma
      virus(M-MSV)-induced tumors, which spontaneously regress due to the generation of
      a strong virus-specific cytotoxic-T-lymphocyte(CTL) response. Repeated systemic
      administration of both MAbs to M-MSV-injected mice enhanced tumor growth and
      delayed regression, while treatment with a single MAb had a similar, though less
      pronounced, effect. The immune depression achieved could not be attributed to
      lymphocyte depletion, because no reduction in the total number of leukocytes was
      detected in the peripheral blood or spleen of these mice. However, anti-LFA-I
      MAb, alone or in combination with anti-ICAM-I MAb, prevented lymphocyte homing in
      tumor-draining lymph nodes. Cytofluorimetric analysis disclosed a profound down
      modulation of LFA-I and ICAM-I molecule expression on T cells following in vivo
      MAb treatment. Moreover, in anti-LFA-I MAb-treated mice, the receptor was coated
      to saturation, while anti-ICAM-I MAb treatment brought about ICAM-I-molecule
      coating levels below saturation. Evaluation of M-MSV-specific CTL precursor (p)
      frequency in lymphoid organs of mice receiving combined MAb treatment showed that
      CTL generation was greatly reduced 10 days after M-MSV injection, and returned to
      control levels by day 15. Our findings indicate that systemic administration of
      MAbs to LFA-I and ICAM-I molecules brings about a strong immune suppressive
      effect which is mainly due to a block in T-lymphocyte re-circulation, and
      activation by tumor cells. However, this immune-depressive effect is only
      temporary, and strictly dependent on continuous MAb administration. Thus, our
      data suggest that treatment with anti-LFA-I and anti-ICAM-I MAbs combined is
      unable to induce T-cell tolerance in a highly immunogenic system.

PMID- 7729949
TI  - High frequency of EBV association with non-random abnormalities of the chromosome
      region 1q21-25 in AIDS-related Burkitt's lymphoma-derived cell lines.
AB  - Chromosome 1q abnormalities represent the second most frequent cytogenetic lesion
      of Burkitt lymphoma (BL) and acute lymphoblastic leukemia (ALL)-L3. The most
      frequent change is partial duplication of the long arm of chromosome 1, involving
      variable bands but consistently including 1q23. Among AIDS-related BL similar
      chromosome 1q abnormalities have also been found. We have now characterized in
      detail the chromosome 1q abnormalities of 4 AIDS-BL cell lines and compared them
      to other molecular features of the tumor clone, namely infection by Epstein Barr
      virus (EBV). Immunophenotypic characteristics were also assessed by conventional
      in situ immunocytochemical and flow cytometric procedures. The B-cell origin of
      all cell lines was demonstrated by the expression of B-cell-restricted markers
      (e.g., CD19). Analysis of Ig light chains confirmed their monoclonal nature. The
      t(8;14) was present in 3 of the 4 lines, whereas variant translocation t(8;22)
      was detected in the remaining cell line. Additional chromosomal changes were
      found in all cases, with chromosome 1 being involved in all. Structural changes
      encompassed in each case the 1q21-25 bands, in either duplication or partial
      trisomy. EBER ISH studies identified EBV association in 3 of the 4 AIDS-BL cell
      lines in contrast to previous studies of BL of immunocompetent individuals. Our
      findings of a high frequency of chromosome 1q abnormalities in EBV-infected AIDS
      related BL cell lines demonstrate that such chromosomal abnormality and EBV
      positivity are not mutually exclusive and are possibly independent factors,
      whereas their close association in AIDS may be related to the immunodeficiency.

PMID- 7729950
TI  - Resistance-associated factors in human small-cell lung-carcinoma GLC4 sub-lines
      with increasing adriamycin resistance.
AB  - Previous studies have shown that the in vitro-selected adriamycin-resistant human
      small-cell lung-carcinoma cell line GLC4-ADR150 displays multidrug resistance as
      the result of 3-fold decreased DNA-topoisomerase II (topo II) activity and a 6
      fold reduction in adriamycin accumulation. Not the MDR1 gene, but the MRP gene,
      was over-expressed in this cell line. The aim of our study was to establish which
      of these drug-resistance-associated factors are already involved in drug
      resistance occurring at early steps of selection with adriamycin. To address this
      question, changes in expression of topo II alpha/topo II beta, MRP and drug
      accumulation were measured along with adriamycin resistance (from 2- to 10- to
      150-fold) and in a partial revertant cell line (10-fold resistant). Topo II alpha
      and II beta mRNA and protein levels were decreased in the resistant sub-lines,
      except in the 10-fold-resistant cell line. Cellular daunorubicin accumulation was
      decreased 1.2- to 5-fold with increasing resistance. MRP mRNA was over-expressed
      in all resistant sub-lines, with a marked increase in the 10-fold-resistant cells
      (level of expression as high as in the GLC4-ADR150 cells). Expression of an ATP
      binding 190-kDa membrane protein and Western-blot analysis with anti-MRP anti
      serum ASPKE, was in accordance with the expression of MRP mRNA in all cell lines.
      Expression of MRP mRNA and protein, however, was not proportional with the
      decrease in drug accumulation in all resistant sub-lines. This study also shows
      that drug accumulation, topo II and MRP expression were all changed at the
      earliest stage of resistance development of GLC4 cells upon adriamycin selection.

PMID- 7729951
TI  - Cdk1 is a marker of proliferation in human lymphoid cells.
AB  - To better understand the relationship between the proliferation of human lymphoid
      cells and the expression of cdk1, a catalytic subunit of the histone H1 kinase
      (H1K), we examined its mRNA and protein content in 3 B-cell lines: Ramos, Reh-6
      and IARC 963. Cells were elutriated according to their position in the cell
      cycle. Cell fractions were analyzed for cdk1 mRNA and protein cellular content by
      Northern blot and immunoblot, respectively, as well as for H1K activity. Both
      mRNA and protein amounts and H1K activity varied according to cell cycle phase,
      the lowest values being observed in G1-enriched fractions. For comparison,
      elutriated fractions were also tested for the expression of cdk2 and cdk4
      proteins. Both showed some variations among fractions, but they were less clear
      than those of cdk1. We also tested 29 samples of lymphoid neoplastic and non
      neoplastic tissues for proliferative activity (percentage of S and G2/M cells
      estimated by flow cytometry) and expression of cdk1, cdk2 and cdk4 proteins. We
      found a significant correlation between the percentage of cells in S or S + G2/M
      phases and cdk1 protein content but not cdk2 or cdk4 content. We conclude that
      cdk1 expression in human lymphoid cells varies during the cell cycle at both mRNA
      and protein levels.

PMID- 7729952
TI  - Induction and characterization of cytotoxic T-lymphocytes recognizing a mutated
      p21ras peptide presented by HLA-A*0201.
AB  - The ras oncogene is frequently found to be activated in human cancer through
      point mutations at codons 12, 13 or 61. We explored whether these altered p21ras
      protein sequences contain peptide sequences that can activate naive CD8+
      cytotoxic T lymphocytes (CTL). Several wild-type and mutated p21ras peptides were
      identified that carry a binding motif for human leukocyte antigen (HLA)-A*0201.
      Two peptides were found to bind strongly to this allele. CD8+ CTL bulk cultures
      specifically reacting with one of these peptides could be induced, using
      processing-defective T2 cells loaded with peptide CLLDILDTAGL as stimulators. The
      peptide is derived from p21ras, position 51-61, and carries a 61 Gln-->Leu
      mutation. In contrast, a 9-mer peptide CLLDILDTA corresponding to amino acid
      sequence 51-59 of wild-type p21ras did not yield reactive CTL cultures. T-cell
      clones with low affinity for the 11-mer peptide were isolated from CLLDILDTAGL
      reactive bulk cultures. These T cells did not lyse melanoma cells transfected
      with 61-Leu N-ras, although lysis was found when these transfectants were pulsed
      with the 11-mer peptide. Possibly, T cells of higher affinity may be required to
      demonstrate processed peptide on the cell surface. The combined experiments
      suggest that a peptide derived from mutated p21ras can be recognized by HLA class
      I-restricted CTL, whereas an analogous wild-type p21ras peptide may not be
      immunogenic.

PMID- 7729953
TI  - Decreased cytotoxic effects of doxorubicin in a human ovarian cancer-cell line
      expressing wild-type p53 and WAF1/CIP1 genes.
AB  - The cytotoxicity of Doxorubicin and cis-dichloro-diammine-platinum (DDP) was
      evaluated in clones, obtained from a human ovarian cancer cell line transfected
      with a temperature-sensitive p53 mutant, which express mutant p53 at 37 degrees C
      and wild-type-like p53 at 32 degrees C. DDP was equally active in cells not
      expressing p53 (SKN) or cells expressing a mutated form of p53 (SK23a kept at 37
      degrees C) or a wild-type-like form of p53 (SK23a cells kept at 32 degrees C). In
      contrast, Doxorubicin was less cytotoxic in cells expressing wild-type p53 than
      in cells expressing no p53 or mutated p53. This reduction was not due to a
      decreased intracellular accumulation or to a faster efflux of Doxorubicin.
      Topoisomerase II was found to be present in the same amount in all the systems
      utilized and to be functionally active, thus not accounting for the observed
      effect of Doxorubicin. A clear induction of WAF1/CIP1 and GADD45 genes in cells
      expressing wild-type p53 after Doxorubicin treatment was found. DDP, which was
      equally active in the cells utilized, caused an increase in the transcription
      only of GADD45 gene but not of WAF1/CIP1 gene. Doxorubicin was also able to
      induce the transcription of WAF1/CIP1 gene in SKN cells (not expressing p53) or
      in SK23a cells at 37 degrees C (expressing mutated p53), indicating that the
      expression of this gene also, in some tumor-cell lines, is not necessarily or
      uniquely induced by wild-type p53.

PMID- 7729954
TI  - Partial circumvention of multi-drug resistance by annamycin is associated with
      comparable inhibition of DNA synthesis in the nuclear matrix of sensitive and
      resistant cells.
AB  - We studied the subcellular and subnuclear distributions of the partially cross
      resistant anthracycline Annamycin (Ann) in KB-3-1 and multi-drug resistant KB-VI
      cells. Subcellular drug localization was assessed qualitatively by fluorescence
      microscopy and quantitatively by cell fractionation and fluorescence
      measurements. Doxorubicin (Dox) localized predominantly in the nucleus in KB-3-1
      cells and in the membranes in KB-VI cells. In contrast, the subcellular
      distribution of Ann was identical in both cell lines, with preferential drug
      localization in the perinuclear region, Golgi apparatus, endoplasmic reticulum
      and endosomes. Dox rate of efflux from the nucleus was negligible in KB-3-1 cells
      but markedly enhanced in KB-VI cells, whereas Ann was lost at a similar rate from
      the nucleus in both cell lines. In KB-3-1 cells Dox levels in the nuclear non
      matrix were about 2-fold higher than those of Ann, while in the matrix the
      inverse relationship was observed. In spite of these differences, Dox and Ann had
      a similar inhibitory effect on new DNA synthesis in the nuclear matrix and non
      matrix of KB-3-1 cells. Dox levels were reduced by 10-fold in the nuclear non
      matrix and 2-fold in the matrix in KB-VI cells compared with KB-3-1 cells,
      whereas Ann levels were reduced by about 2- to 3-fold in the non-matrix and were
      unchanged in the matrix. In correlation with these findings, Dox did not cause
      inhibition of new DNA synthesis in either nuclear fraction in KB-VI cells,
      whereas inhibition of new DNA synthesis in the matrix by Ann was similar in both
      cell lines. Our results indicate that Ann's partial circumvention of multi-drug
      resistance is associated with its ability to cause comparable new DNA synthesis
      inhibition in the nuclear matrix of sensitive and resistant cells.

PMID- 7729955
TI  - Modulation of growth and proliferation in squamous cell carcinoma by retinoic
      acid: a rationale for combination therapy with chemotherapeutic agents.
AB  - We have previously shown that beta-all trans retinoic acid (RA) inhibits
      macrocellular growth of a multicellular tumor spheroid model for squamous
      carcinoma, as measured by spheroid size, but allows for continuing DNA synthesis
      and cell cycle progression, the two being reconciled by a cell death effect. DNA
      synthesis in the presence of growth inhibition suggested a rationale for
      examining combination chemotherapy with RA-inhibited cells. To this aim, we have
      extended this observation to a series of 8 squamous carcinoma cell lines. Cells
      were treated with 1 microM RA for 7 days and cell growth parameters monitored.
      Although growth inhibition ranged from 0% (A431) to approx. 80% (MDA 886Ln), [3H]
      thymidine incorporation (cpm/microgram protein) and percent S-phase (by flow
      cytometry) in 7-day RA-treated cells was equal or higher than in their control
      vehicle-treated cells in 7/8 SCC cell lines. Thus RA-induced growth inhibition is
      not just cytostasis. Combination therapy was examined with MDA 886Ln, MDA 686Ln,
      1483 and A431 cells pre-treated for 7 days with 1 microM RA followed by cisplatin
      or 5-fluorouracil treatment. An increased effectiveness for the combination was
      shown using 5-day tetrazolium dye (MTT) growth assays when cells were growth
      inhibited by RA. Computerized analysis of data using median-effect and
      isobologram techniques indicated that the interaction of RA with these
      chemotherapeutic agents was synergistic. With squamous carcinoma, RA treatment
      inhibits growth while allowing for continuing DNA synthesis, and these RA
      treated, growth-inhibited cells exhibit increased sensitivity to chemotherapeutic
      agents.

PMID- 7729956
TI  - Interleukin-3: a putative protective factor against breast cancer which is
      secreted by male but not female breast fibroblasts.
AB  - The enzyme 17 beta-hydroxysteroid dehydrogenase (17-HSD) is a key regulator of
      intracellular 17 beta-estradiol (E2), which is associated with breast cancer and
      is influenced by paracrine factors released by breast-cancer fibroblasts. Since
      the incidence of breast cancer is much higher in females than in males, we have
      used an in vitro cell culture system to investigate whether male fibroblasts may
      inhibit breast-cancer genesis by restricting the intracellular accumulation of
      E2. Fibroblasts were obtained from normal males and females undergoing reduction
      mammoplasty, and from females with benign or malignant breast lesions. Fibroblast
      conditioned medium (CM) was incubated with the established breast-cancer cell
      line, MCF-7, and its effects on 17-HSD activity were assessed. CM (25% v/v) from
      male breast fibroblasts had a significant inhibitory effect on reductive 17-HSD,
      decreasing E2 production. This was in direct contrast to the effects of CM from
      female breast fibroblasts, which had a powerful stimulatory effect on reductive
      17-HSD. RT-PCR allowing simultaneous detection of a range of cytokines was
      performed on each type of fibroblast. IL-3 mRNA was consistently detected in
      fibroblasts from male but not female breast tissue. Addition of rhIL-3 to
      cultures of MCF-7 caused a reduction in 17-HSD activity and addition of a
      polyclonal antibody directed against IL-3 to male CM completely reversed the
      inhibitory effects of CM. Thus, male breast fibroblasts may be responsible for
      secreting IL-3-like factors which, given the considerably lower incidence rates
      of breast cancer in men, may have a protective effect against breast cancer.

PMID- 7729957
TI  - Systemic effects of cytokines released by gene-transduced tumor cells: marked
      hyperplasia induced in small bowel by gamma-interferon transfectants through host
      lymphocytes.
AB  - Cells transduced with cytokine genes are currently used to enhance the anti-tumor
      and immunomodulatory effects of these molecules in cancer therapy. The sustained
      release of cytokine thus obtained can perturb many homeostatic systems of the
      host. We have previously shown that the murine mammary adenocarcinoma TS/A
      transfected with the murine gamma-interferon (IFN-gamma) gene stimulates a strong
      immune response that impairs tumor growth. Mice bearing tiny tumors have serum
      IFN-gamma levels constantly exceeding 100 IU/ml. Therefore, we asked which
      systemic effects can be triggered in mice by such transfectants. BALB/c mice
      bearing tumors produced by clone 16.6000 cells (which release 6,000 IU/ml of IFN
      gamma in culture) were compared to normal mice and to mice with tumors produced
      by parent cells transfected with the neomycin resistance gene (NEO cells, no IFN
      gamma release). Histological studies revealed a marked hyperplasia of small bowel
      in mice bearing 16.6000 tumors; the villi and crypts of these mice were > 1.5
      times longer than those of normal mice and of mice bearing NEO tumors. In vivo
      administration of bromodeoxyuridine evidenced a 2.5-3 times increase in the
      proliferative score of the intestinal crypts of mice bearing 16.6000 tumors
      compared to control mice. No intestinal alterations were observed in nude mice
      bearing 16.6000 tumors. T lymphocytes thus appear to play a causal role in this
      phenomenon.

PMID- 7729959
TI  - The von Hippel-Lindau (VHL) disease tumor-suppressor gene is not mutated in
      nasopharyngeal carcinomas.

PMID- 7729958
TI  - Mechanism of cross-resistance to cisplatin in a mitomycin C-resistant human
      bladder cancer cell line.
AB  - This study was undertaken to elucidate the mechanism(s) of cross-resistance to
      cisplatin (CDDP) in a mitomycin C (MMC)-resistant human bladder cancer cell line,
      J82/MMC. The J82/MMC cell line displayed 2- to 3-fold cross-resistance to CDDP
      and carboplatin when compared to the parental J82/WT cells. Drug uptake studies
      revealed that cross-resistance to CDDP in the J82/MMC cell line was independent
      of reduced platinum accumulation. The J82/MMC cell line exhibited approximately a
      1.5-fold resistance to cadmium chloride, an indicator for increased
      metallothionein (MT) content, when compared to the J82/WT cells. Northern blot
      analysis showed a 2.7-fold higher level of MT-IIA mRNA in the J82/MMC cell line
      compared with J82/WT. We have reported previously that, whereas glutathione (GSH)
      level is comparable in these cells, GSH transferase (GST) activity is
      significantly higher in the J82/MMC cell line compared with J82/WT. Results of
      the present study showed that the elevated GST activity in the J82/MMC cell line
      was due to an over-expression of pi-type GST protein. Although buthionine-S,R
      sulfoximine (BSO)-induced GSH depletion significantly enhanced CDDP cytotoxicity
      in both cell lines, the magnitude of potentiation was markedly higher in J82/MMC
      cells (about 2.1-fold) relative to J82/WT (about 1.6-fold). Our results suggest
      that cross-resistance to CDDP in the J82/MMC cell line may be due to alterations
      in cellular thiols.

PMID- 7729960
TI  - Twenty-fifth anniversary: an interview with Vicente Navarro, Editor-in-Chief.

PMID- 7729961
TI  - Capital sectors and workers' health and safety in the United States.
AB  - The dual or segmented economy perspective suggests that the U.S. production
      system within a capitalist world-system can be divided into distinct sectors
      based on elements such as levels of industrial concentration, foreign
      involvement, and unionization. The differing organization of these sectors is
      argued to influence worker health and safety (WHS) outcomes. An economic
      segmentation model was applied to national occupational health data to examine
      the relationship between structural divisions in the economy and occupational
      hazard exposure, injury, and illness. Workers in more global industrial sectors
      had only average levels of hazardous exposure but a greater likelihood of
      occupational injury and illness than workers in other sectors of the economy.
      These differences are related to the structure of work in the various sectors.
      The findings suggest the need for (1) greater surveillance and reporting of WHS
      problems through the general health care system; (2) planning of economic and
      productive activity that takes WHS issues into account; and (3) greater worker
      organization and power within and between nations to improve WHS.

PMID- 7729962
TI  - A perspective on the corporate transformation of health care.
AB  - The ever-increasing ownership of health service providers, suppliers, and
      insurers by investor-owned enterprises presents an unforeseen complexity and
      diversity to health care delivery. This article reviews the history of the for
      profit invasion of the health sector, linking corporate purchaser directions to
      the now dominant mode of delivery in managed care. These dynamics require
      unceasing reassessment while the United States embarks upon implementation of
      national health care reform.

PMID- 7729963
TI  - A conversation about the work environment.
AB  - The author looks at work environment matters from the perspective of public
      policy-making and the policy instruments used to deal with workplace health and
      safety: standard setting; joint health and safety committees; compliance,
      enforcement, and prosecution; workers' compensation as an economic incentive; and
      collective bargaining. While regarding all as necessary, the author considers
      them as separately and collectively, fundamentally flawed and therefore
      insufficient, because liberal public policy-making itself is problematic. He
      proposes an alternative way of thinking about this subject from the perspective
      of the "politics of meaning."

PMID- 7729964
TI  - The role of organized labor in combating the hepatitis B and AIDS epidemics: the
      fight for an OSHA bloodborne pathogens standard.
AB  - The United States is experiencing a hepatitis B epidemic that has until recently
      received relatively little public attention. Many groups of workers are at risk
      of infection, death, or chronic carriership because of workplace exposure to
      blood; those at risk include not only health care professionals but police, fire
      fighters, life guards, hospital-based laundry and cafeteria workers, park
      rangers, sanitation workers, etc. One of the most important victories against the
      hepatitis B pandemic in the United States occurred when the Occupational Safety
      and Health Administration issued a Bloodborne Pathogens Standard that required
      employers to protect 5 1/2 million workers from infection by offering those at
      risk free hepatitis B vaccination, and forced employers to bear the costs of
      providing equipment (e.g., gloves, gowns, masks, puncture-proof containers) to
      maintain "universal precautions" for employees handling bodily fluids. While most
      people assume the new standard was primarily aimed at fighting the AIDS epidemic,
      it was actually based on the more significant risk posed by hepatitis B
      infection. The standard resulted not from leadership provided by the experts in
      the Public Health Service mandated to control infectious disease, but rather from
      pressure applied by labor unions--providing a clear example of the continued
      importance of unions for worker protection in our supposedly post-union era.

PMID- 7729965
TI  - The health left in the 1930s, 1940s, and 1950s.
AB  - To go back to a period more than five decades ago to talk about the health left
      is to enter not just another time, but another world. Between the Great
      Depression and the postwar period, challenging and contradictory social,
      political, and professional developments were brought to the surface in U.S.
      life. The health left shared in the opportunities and confusion, enriching the
      American spirit and participating in both the pleasures and the pain. The 1930s
      saw economic depression, wars, the birth of fascism, and fears of social
      collapse. In medicine, despite sporadic scientific advances, the social response
      was remote and narrow. But social activism motivated medical students and medical
      practitioners. The 1940s marked a change in both attitudes and values. The left
      was divided, and bitter factionalism stymied cooperative action. Participation in
      the war against fascism promoted solidarity, despite the sadness of the evidence
      of brutality and lack of humanity. The 1950s are sometimes considered regressive,
      but seeds germinated as the complexity of medical life engendered new approaches
      to meeting sociomedical needs. As we entered the 1960s a different and more
      hopeful story unfolded as the rebellions of the poor, blacks, and women brought
      about a new era of social action.

PMID- 7729966
TI  - Killing the beast within: woman battering and female suicidality.
AB  - This article explores the importance of woman battering for female suicidality,
      with special attention to the link among black women. Suicidality has classically
      been framed with a distinctly male bias. As a result, suicide attempts (a
      predominantly female event) have been defined as "failed suicides" and the
      distinctive social context of suicidality among women has been missed. The
      authors propose that suicidality among battered women is evoked by the
      "entrapment" women experience when they are subjected to "coercive control" by
      abusive men. A literature review highlights the probable importance of male
      violence as a cause of female suicidality. Pursuing this possibility, we assess
      the significance of battering in a sample of women who have attempted suicide,
      the characteristics of battered women who attempt suicide, and the
      appropriateness of the medical response. The results indicate that battering may
      be the single most important cause of female suicidality, particularly among
      black and pregnant women. The implications of this finding for theory and
      clinical intervention are discussed.

PMID- 7729968
TI  - The class analysis of poverty.
AB  - To understand more fully the nature of poverty it must be viewed as the result,
      in part, of inherent features of the social system. The author describes four
      general approaches to explaining poverty: poverty as a result of inherent
      individual attributes, as the by-product of contingent individual
      characteristics, as a by-product of social causes, and as a result of inherent
      properties of the social system. He then elaborates a class exploitation analysis
      of poverty by explaining how economic oppression, economic exploitation, and
      class generate a social system in which poverty plays a crucial functional role.
      The general problem of poverty must be broken down into two subproblems: poverty
      generated inside exploitative relations (the working poor) and poverty generated
      by nonexploitative oppression (the underclass). A class analysis of poverty
      argues that significant numbers of privileged people have a strong, positive
      material interest in maintaining poverty. Poverty can be reduced in the United
      States only through popular mobilization of pressure that challenges the power of
      the dominant classes.

PMID- 7729967
TI  - Selective abortion: a new moral order? Consensus and debate in the medical
      community.
AB  - The authors discuss the results of a survey of the attitudes of Canadian and
      French (Picardie, Nord-Pas de Calais) physicians toward selective abortion of
      fetal anomalies detected by ultrasound, amniocentesis, or chorionic villus
      sampling. The study documents the threshold of acceptability of abortion of
      fetuses with selected anomalies, as well as the physicians' own perceptions of
      their role in the decision to abort. While there was no consensus among all
      Canadian physicians regarding the acceptability of abortion, more than 55 percent
      from France and Quebec would accept selective abortion of a fetus affected with
      trisomy 21, Duchenne muscular dystrophy, cystic fibrosis, Huntington's chorea, or
      spina bifida. In the province of Quebec, Anglophone physicians showed a greater
      acceptance of abortion than did their French-speaking colleagues. In reference to
      the physician's role in the decision to abort, French physicians are more
      directive than North American physicians. Cultural predispositions may explain
      these differences in attitudes.

PMID- 7729969
TI  - Special issue: The rise and decline of animal parasites, on the occasion of the
      retirement of professor J. F. A. Sprent.

PMID- 7729970
TI  - Ancient biochemistries and the evolution of parasites.
AB  - The characteristic respiratory metabolism of parasites consists of fermentation
      to carbon-rich, highly reduced volatile fatty acids which are excreted, and
      electron transport systems emphasising fumarate reductase and b-type cytochromes.
      The taxonomic groups that contribute major parasites (the heterogeneous protozoa
      and the helminths) have their evolutionary origins in environments from which
      oxygen was absent or present in very low concentrations. The Ediacarian period,
      about 700 million years ago, contains fossils of the appropriate grade of
      organisation to be contemporaneous with the ancestors of platyhelminths,
      nematodes and acanthocephalans. With the oxygen transition, carbon flow in the
      biosphere resulted in conservative, anoxic environments together with oxygen rich
      ones. The organisms of the former retained their emphasis on anaerobic energy
      generation, while cytochrome systems were as much concerned with oxygen
      detoxification as energy generation. Metabolic pathways in the modern parasitic
      groups are echoes of such ancient biochemistries.

PMID- 7729971
TI  - The origins of parasitism in the platyhelminthes.
AB  - Symbiotic associations have arisen independently in several groups of the largely
      free-living turbellarians. Morphological adaptations of turbellarians to a
      symbiotic way of life include suckers and adhesive glands for attachment,
      elaborate systems of microvilli and other epidermal structures for absorption of
      food, glands for the formation of cysts, cocoons and cement material, and lack of
      a pharynx and intestine in some species. However, many species closely resemble
      their free-living relatives. Egg production is greatly increased at least in some
      species, and life cycles are always direct. Food of symbiotic turbellarians
      consists of host food and/or host tissue. Ectosymbiotes show fewer physiological
      adaptations than entosymbiotes. The major groups of parasitic Platyhelminthes
      (Trematoda Aspidogastrea, Trematoda Digenea, Monogenea, Udonellidea, Cestoda
      including Gyrocotylidea, Amphilinidea and Eucestoda), form one monophylum, the
      Neodermata, characterized by a neodermis (tegument) replacing the larval
      epidermis, epidermal cilia with a single horizontal rootlet, sensory receptors
      with electron-dense collars, spermatozoa with axonemes incorporated in the sperm
      body by proximodistal fusion, and protonephridial flame bulbs formed by two cells
      each contributing a row of longitudinal ribs to the filtration apparatus. The
      sister group of the Neodermata is unknown but is likely to be a large taxon
      including the Proseriata and some other turbellarian groups. Among the
      Neodermata, the Aspidogastrea is likely to be the most archaic group, as
      indicated by DNA studies, morphology, life cycles and physiology. Aspidogastreans
      can survive for many days or even weeks outside a host in simple media, they show
      little host specificity, and have an astonishingly complex nervous system and
      many types of sensory receptors, both in the larva and the adult. It is suggested
      that Aspidogastrea were originally parasites of molluscs (and possibly arthropods
      and other invertebrates) and that they are archaic forms which have remained at a
      stage where vertebrates represent facultative hosts or obligatory final hosts
      into which only the very last stages of the life cycle (maturation of the gonads)
      have been transferred. The complex life cycles of Digenea have evolved from the
      simple aspidogastrean ones by intercalation of multiplicative larval stages
      (sporocysts, rediae) in the mollusc host, and of cercarial stages ensuring
      dispersal to the now obligatory final host. Monogenea may have lost the molluscan
      host or evolved before the early neodermatans had acquired it. Cestoda either
      replaced the original molluscan with an arthropod host, retained an original
      arthropod host or evolved from an early neodermatan before molluscan hosts had
      been acquired, newly acquiring an arthropod host.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7729972
TI  - Origins of the parasitic habit in the nematoda.
AB  - Circumstances that probably attended and influenced the adoption and development
      of the parasitic habit amongst the Nematoda are examined. Features that allowed
      early terrestrial nematodes to exploit discontinuous habitats such as decomposing
      organic matter, are considered to have been advantageous to microbivorous
      Secernentea that became parasites of animals and plants. This development
      followed the appearance of a land flora and that the Amphibia were the first
      vertebrate hosts of nematodes. Life cycles involving intermediate hosts were
      essential in drier environments and in a aquatic ones where intermediate hosts
      preserve the infective stages; keeps them "in circulation", and makes them
      attractive to predators. It is concluded that the parasitic habit was adopted
      repeatedly in both Secernentea and Adenophorea, though the latter did not
      diversify as much. Convergence is a common feature of nematode evolution, and the
      typical life history pattern of 5 stadia separated by 4 moults is often greatly
      modified by suppression, extension and diversification of stages and their roles.
      There is a need to examine the nematodes, especially of invertebrates in the
      remaining rain forests of Gondwanaland before they disappear.

PMID- 7729973
TI  - The origins of parasitism in the protists.
AB  - The origins of parasitism among the protists are, like the group itself,
      polyphyletic. Probably the majority of present-day parasitic forms evolved from
      free-living ancestors which were ingested as part of the food of their hosts,
      though origins from ectoparasitic forms and via a phase of facultative parasitism
      are possibilities, particularly among the ciliated protozoa and (for
      ectoparasitism) the Kinetoplasta. Sporozoan parasites most probably developed via
      a stage which was ingested and became adapted to life in the host's gut. Further
      developments in parasitism involved deeper penetration into the host's tissues
      and the adoption of more than one host in the life cycle, thus avoiding entirely
      the potentially hazardous phase of existence outside the host.

PMID- 7729974
TI  - The origins and evolutionary expansion of the Strongylida (Nematoda).
AB  - The Strongylida are thought to have arisen from free-living rhabditoid nematodes,
      but the relationships between the major groupings within the Strongylida, the
      Strongylina, the Metastrongylina, Trichostrongylina and the Ancylostomatina are
      far from clear in spite of the abundance of morphological data now available for
      analysis. Evolutionary mechanisms including co-evolution, host switching, host
      dispersal, use of intermediate hosts, various sites of localisation within the
      definitive host and modifications of life-cycle strategies appear to have been
      utilised in the expansion of the Strongylida, with different mechanisms
      predominating in different families or superfamilies. Co-evolution appears to
      have been a major mode of evolution in the Strongylina, in contrast to the
      Trichostrongylina, which have used host dispersal and host-switching to great
      advantage. The phylogeny of the Ancylostomatina shows little association with
      host evolution, but does match the feeding preferences of the hosts. The
      Metastrongylina have utilised intermediate hosts and life cycle modifications
      including a shift to extra-intestinal sites as major means of diversification, in
      contrast to the other sub-orders. The review, while indicating much progress in
      our understanding of the phylogeny of the Strongylida, also reveals that enormous
      gaps still exist, and emphasises the tentative nature of many of the phylogenetic
      hypotheses tendered to date.

PMID- 7729975
TI  - Evolutionary patterns in life histories of Oxyurida.
AB  - The Oxyurida comprises some 850 known species that occur in the intestine of
      arthropods and vertebrates (one species in annelids). Important arthropod hosts
      include Diplopoda, Blattodea, Gryllotalpoidea, Passalidae, Scarabaeida and
      Hydrophilidae. The major vertebrate hosts are lizards, tortoises, primates,
      rodents and lagomorphs. An underlying characteristic of the group is haplodiploid
      reproduction and like many haplodiploid groups, pinworms tend to have life
      histories that involve high levels of inbreeding. Unlike Strongylida, Ascaridida
      and Spirurida, which have diversified in tissue site and life cycle as well as
      hosts, pinworms show little variation in these features and have radiated only
      across host groups. Two explanations are advanced for this. Haplodiploidy and its
      concomitant inbreeding may act to canalise evolutionary change, although diverse
      groups such as the Hymenoptera belie this. Alternatively, Strongylida, Ascaridida
      and Spirurida are presumed to have arisen from skin-penetrating ancestors that
      were forced to undergo a tissue migration before reaching their primitive tissue
      site, the gut. This migration demanded they adapt to a variety of tissue sites
      and thus acted as a preadaptation to further diversification. The Oxyurida, in
      contrast, probably arose using oral contaminative transmission. The lack of
      exposure to other tissue sites may therefore have relegated pinworms to their
      position in the posterior gut.

PMID- 7729976
TI  - The evolutionary expansion of the Spirurida.
AB  - The possible origins of the 12 superfamilies of the Spirurida are considered,
      based on comparative morphology, host and geographic distributions. The available
      evidence suggests a complex origin of these nematodes, some families being
      derived from the Seuratoidea, and others from the Cosmocercoidea (Ascaridida).
      The spirurid radiation is an old one and seems to have occurred primarily in the
      Secondary or early Tertiary eras. Since then, expansion has occurred with host
      capture as a prominent mechanism. The Dracunculoidea Procamallanidae and
      Camallanidae are probably derived from the Chitwoodchabaudiidae and the
      Rictularioidea from the Schneidernematidae. The Seuratidae may have given rise to
      the Gnathostomatoidea, the Physalopteroidea, the Thelazioidea, the
      Habronematoidea, the Spiruroidea and the Acuarioidea. The filarioid nematodes
      appear to have several origins with the Diplotriaenoidea derived from the
      Spiruroidea, while constituents of the Aproctoidea derived from the
      Cystidicolinae, the Seuratoidea and the Spiruroidea. The Filarioidea are thought
      to have arisen from the Spiruroidea and the Thelazioidea. The evolution of tissue
      parasitism as a secondary phenomenon is considered in various groups.

PMID- 7729977
TI  - Transberingian dispersal of cestodes in mammals.
AB  - During Pleistocene glaciations, eustatic lowering of sea-level exposed the
      continental shelf between northeastern Eurasia and northwestern North America.
      That land in combination with unglaciated areas on the adjacent continents formed
      a vast region open to the west but bounded on the east by continental ice.
      Organisms from Eurasia spread into the unglaciated Beringian refugium, which was
      biotically an eastward extension of the Palaearctic. With rising sea-levels
      following glacial periods, the Bering Strait was formed and organisms of Eurasian
      origin were left within the nearctic sector of Beringia. As the continental ice
      disappeared, plants and animals spread eastward and southward from Beringia,
      while organisms from beyond the southern margins of the ice extended their ranges
      northward. The significance of Beringia is discussed with reference to the
      dispersal of host-specific cestodes in mammals that attained holarctic status
      during the late Pleistocene.

PMID- 7729978
TI  - The evolutionary expansion and host-parasite relationships of the Digenea.
AB  - Relevant data on the Digenea extracted from a host-parasite data-base are
      analysed in relation to host-groups, host-specificity, speciation, radiation and
      geographical distribution. The classification, evolution, co-evolution, and co
      speciation of the group are discussed. Principal components analyses indicated
      that 119 families formed 11 groups in relation to their vertebrate hosts and the
      55 families with molluscan records formed 6 groups in relation to their molluscan
      hosts. The most prominent host-groups are the Fish and Mammals. Individual
      digenean families did not exhibit the host combinations Fish+Birds, Fish+Mammals,
      Herpetiles+Birds and Herpetiles+Mammals. Families with Fish hosts tended to use
      Prosobranch and, to a lesser extent Bivalve, molluscs, whereas families in
      Herpetiles, Birds and Mammals tended to use Pulmonates. Families using 3 or 4
      mixed vertebrate groups tended to use mixed molluscan groups. Families using
      Herpetiles as the vertebrate host tend to be the most host-specific and the least
      speciose, whereas those using 3 to 4 mixed vertebrate groups are the most
      speciose. In a detailed examination of three zoogonid genera, few indications of
      co-evolution with their vertebrate hosts were detected, and geographical
      information from the data-base appeared to shed no light upon the geographical
      origins of the Digenea. Some of these findings are commented upon in relation to
      the evolution of the Digenea.

PMID- 7729979
TI  - Evolutionary expansion of the Monogenea.
AB  - The evolutionary expansion of the monogeneans has taken place in parallel with
      the diversification of the fish-like vertebrates. In this article the main trends
      in monogenean evolution are traced from a hypothetical skin-parasitic ancestor on
      early vertebrates. Special consideration is given to the following topics: early
      divergence between skin feeders and blood feeders; diversification and
      specialization of the haptor for attachment to skin; transfer from host to host,
      viviparity and the success of the gyrodactylids; predation on skin parasites and
      camouflage; colonization of the buccal and branchial cavities; diversification
      and specialization of the haptor for attachment to the gills; phoresy in gill
      parasites; the development of endoparasitism and the origin of the cestodes; the
      success of dactylogyroidean gill parasites; the uniqueness of the
      polyopisthocotyleans; ovoviviparity and the colonization of the tetrapods. Host
      specificity has been the guiding force of coevolution between monogeneans and
      their vertebrate hosts, but the establishment of monogeneans on unrelated hosts
      sharing the same environment (host-switching) may have been underestimated. Host
      switching has provided significant opportunities for evolutionary change of
      direction and is probably responsible for the establishment of monogeneans on
      cephalopod molluscs, on the hippopotamus and possibly on chelonians. There are
      indications that host-switching may be more common in monogeneans that spread by
      direct transfer of adults/juveniles from host to host. A limitation on the
      further expansion of monogeneans is the need for water for the dispersal of the
      infective larva (oncomiracidium).

PMID- 7729980
TI  - Adaptation, specificity and host-parasite coevolution in mites (Acari).
AB  - Parasitism by mites is widespread and involves all the classes of vertebrates,
      from fishes to mammals. Owing to their small size and their great plasticity,
      mites are able to adapt to a wide range of habitats. Most of the species are
      ectoparasites but endoparasitism, especially in the respiratory tract, is common
      in birds and mammals. The morphological modifications appearing during the
      process adaptation to parasitic life, especially in Myobiidae, are analysed. Two
      kinds of characters are particularly important: the constructive specialized
      characters, consisting of the production of new structures, especially attachment
      organs allowing the mite to attach to the skin and the hair of the host, and
      regressive characters. Regression of the external structures is the most
      important phenomenon appearing in the process of evolution of parasitic mites.
      The importance of the regression in the parasite is correlated with the degree of
      evolution of the host. Host and parasite have a parallel evolution, but they go
      in opposite directions. The author surmises that the regressive evolution is
      related to the immunological reactions of the host that tend to reject the
      parasite. To escape from this rejection the parasite tends to select the less
      antigenic and therefore the most regressed phenotype. Specificity is generally
      strict in permanent parasites. Coevolution of host and parasite is studied in the
      family Myobiidae which parasitizes marsupials, insectivores, bats and rodents.
      The concordance between the radiations of the mites and that of their hosts is
      very high.

PMID- 7729981
TI  - Phylogeny and classification, origins, and evolution of host associations of
      lice.
AB  - Lice are highly successful ectoparasites. Most species of mammals and birds are
      infested by at least 1 but up to 6 species of lice. Current opinion is that lice
      evolved from free-living Psocoptera (booklice, barklice and psocids). It is
      generally agreed that there are 4 main groups of lice: Anoplura, Amblycera,
      Ischnocera and Rhyncophthirina. In contrast, there is no agreement on the
      phylogenetic relationships of these groups and their classification. In
      particular, there is much debate over the validity of the taxon Mallophaga, which
      is almost certainly paraphyletic. For many years the sister-group of the
      Boopiidae, which almost exclusively infest Australasian marsupials, was thought
      to be a group of lice that now infest marsupials in South America. This, however,
      is almost certainly incorrect; the sister-group of the Boopiidae probably
      contains bird-infesting lice from the Menoponidae (Amblycera). Thus, menoponid
      lice transferred from birds to mammals and from these arose the Boopiidae.
      Transfers of lice between mammals and birds have occurred on other occasions
      during the evolution of the lice; 2 of the 4 main groups of lice, the Ischnocera
      and Amblycera, contain families that infest birds and families that infest
      mammals. Strict cospeciation and coevolution was thought to predominate among the
      lice; however, detailed studies indicate this to be incorrect. Consequently, the
      axiom that lice and their hosts invariably coevolve should be abandoned.
      Ironically, biologists may learn more about the evolutionary biology of hosts
      when host-switching has occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7729982
TI  - Origin and evolution of the parasitic cyclopoid copepods.
AB  - Six of the 10 recognised families of the order Cyclopoida are parasitic, with 4
      of them occurring on marine invertebrates and the remaining 2 on freshwater
      gastropods and fishes, respectively. A cladistic analysis of the 10 families
      indicates that evolution of parasitism occurred twice in the history of the
      cyclopoids. The first attempt was made by the marine epibenthic ancestors seeking
      food and shelter in sessile tunicates--the ascidians. This event led to the
      evolution of 2 ascidicolous families: Archinotodelphyidae and Notodelphyidae. The
      descendant of this lineage had also invaded the mantle cavity of marine bivalve
      molluscs, eventually leading to the evolution of the Mantridae. The second
      attempt for the parasitic mode of life was launched by the ancestor which was the
      sister group of the ancestral cyclopoids--the most successful family of
      freshwater copepods. This ancestral stock, while living in the coastal zone,
      split into 2 groups: one group stayed behind in the ocean and colonised again the
      ascidians; the other groups invaded freshwater and evolved into the fish
      parasitising Lernaeidae and the gastropod-parasitising Ozmanidae.

PMID- 7729983
TI  - The evolutionary expansion of the Sporozoa.
AB  - The sporozoans comprise a coherent group of protozoans, with characteristic and
      complex life cycles, containing 4-5000 species parasitic in invertebrates,
      particularly annelids and arthropods, and vertebrates. The group is a very
      successful one but neither its origins nor evolution are well understood.
      Considerations of traditional life cycles combined with newer methodologies have
      thrown some light on the evolutionary expansions of the main groups of
      sporozoans, the gregarines, coccidia, haemosporidians and piroplasms. The
      sporozoans of economic importance such as the coccidia, malaria parasites and
      piroplasms have received most attention but the data obtained have also thrown
      new light on the possible evolution of less well studied groups and it is
      concluded that conclusions based on simple comparisons of life cycles will have
      to be modified. It is also clear that humans have played a major part in
      affecting the distribution and present abundance of many sporozoans of economic
      significance and probably also those of less importance, and that the rates of
      evolutionary expansion are much more rapid than previously thought.

PMID- 7729984
TI  - The evolutionary expansion of the trypanosomatid flagellates.
AB  - The trypanosomatids combine a relatively uniform morphology with ability to
      parasitise a very diverse range of hosts including animals, plants and other
      protists. Along with their sister family, the biflagellate bodonids, they are set
      apart from other eukaryotes by distinctive organisational features, such as the
      kinetoplast-mitochondrion and RNA editing, isolation of glycolysis enzymes in the
      glycosome, use of the flagellar pocket for molecular traffic into and out of the
      cell, a unique method of generating cortical microtubules, and bizarre nuclear
      organisation. These features testify to the antiquity and isolation of the
      kinetoplast-bearing flagellates (Kinetoplastida). Molecular sequencing techniques
      (especially small subunit ribosomal RNA gene sequencing) are now radically
      reshaping previous ideas on the phylogeny of these organisms. The idea that the
      monogenetic (MG) trypanosomatids gave rise to the digenetic (DG) genera is losing
      ground to a view that, after the bodonids, the African trypanosomes (DG)
      represent the most ancient lineage, followed by Trypanosoma cruzi (DG), then
      Blastocrithidia (MG), Herpetomonas (MG) and Phytomonas (DG), with Leptomonas
      (MG), Crithidia (MG), Leishmania (DG) and Endotrypanum (DG) forming the crown of
      the evolutionary tree. Vast genetic distances (12% divergence) separate T. brucei
      and T. cruzi, while the Leishmania species are separated by very short distances
      (less than 1% divergence). These phylogenetic conclusions are supported by
      studies on RNA editing and on the nature of the parasite surface. The
      trypanosomatids seem to be able to adapt with ease their energy metabolism to the
      availability of substrates and oxygen, and this may give them the ability to
      institute new life cycles if host behaviour patterns allow. Sexual processes,
      though present in at least some trypanosomatids, may have played only a minor
      part in generating diversity during trypanosomatid evolution. On the other hand,
      the development of altruistic behaviour on the part of some life cycle stages may
      be a hitherto unconsidered way of maximising fitness in this group. It is
      concluded that, owing to organisational constraints, the trypanosomatids can
      undergo substantial molecular variation while registering very little in the way
      of morphological change.

PMID- 7729985
TI  - Host fragmentation and helminth parasites: hedging your bets against extinction.
AB  - We consider the probability of parasite extinction due to anthropogenic
      fragmentation of host populations and in the absence of host extinction. We
      conclude that extinction at infrapopulation and infracommunity levels is both
      common and trivial. Extinction may occur in communities at higher levels but only
      if metapopulations or suprapopulations become extinct. Suprapopulations are
      highly complex and unlikely to become extinct in the face of simple host
      fragmentation. We acknowledge parasite metapopulations as being the most likely
      to become extinct, but only locally. Our reasoning for this is that, in the
      absence of complete host extinction, populations of the parasite in other
      fragments are likely to serve as sources for reinvasion (e.g. a rescue effect).
      We identify a number of features that may act as hedges against extinction for
      many parasites and conclude by attempting to identify what form an extinction
      might take.

PMID- 7729986
TI  - Post-operative morbidity following paediatric tonsillectomy; a comparison of
      bipolar diathermy dissection and blunt dissection.
AB  - In a prospective study of 76 children aged between 18 months and 13 years, 40
      children underwent tonsillectomy using the traditional blunt dissection technique
      with bipolar diathermy to establish haemostasis while 36 children underwent
      tonsillectomy where bipolar diathermy alone was used to dissect out the tonsils.
      Blood loss was significantly reduced in the diathermy dissection group (10.5 ml
      +/- 2.05, diathermy dissection, 33.56 ml +/- 1.95, blunt dissection, P < 0.05).
      More analgesia was required in the diathermy dissection group prior to hospital
      discharge (P = 0.01). The diathermy dissection group took a significantly longer
      period of time to re-establish a normal diet (7.07 days +/- 0.44, diathermy
      dissection, 5.15 days +/- 0.36, blunt dissection, P = 0.001). Fifteen percent of
      children in the blunt dissection group and 31% in the diathermy dissection group
      were taken to the general practitioner between days 3-10 because of sore throat,
      poor oral intake or otalgia. Twenty two point four percent of children overall
      were prescribed antibiotics. This recently described technique of bipolar
      diathermy dissection could be a useful technique in selected cases such as the
      very small or those with a bleeding diathesis but is associated with increased
      postoperative morbidity and requires good postoperative analgesia.

PMID- 7729987
TI  - The role of MRI when relapsing polychondritis is suspected but not proven.
AB  - Relapsing polychondritis (RP), while relatively rare, presents a characteristic
      clinical picture. Based upon a symptom complex of auricular, nasal, and
      respiratory chondritis associated with ocular and otic complaints, diagnosis can
      frequently be made with confidence in the absence of histologic confirmation. We
      present a case where a therapeutic intervention was required without sufficient
      criteria for diagnosis. Magnetic resonance imaging (MRI) proved useful in initial
      evaluation and allowed follow-up imaging demonstrating a gratifying response to
      steroid treatment. We believe that MRI has an important role in the diagnosis and
      subsequent evaluation of patients with proven or suspected RP, particularly those
      with tracheal involvement.

PMID- 7729988
TI  - Diagnosis and management of laryngeal obstruction in childhood pachyonychia
      congenita.
AB  - Pachyonychia congenita is a genetic syndrome of epithelial dysplasia. In infants
      and young children, laryngeal involvement can present a life threatening
      complication: obstruction of the patient's airway due to leukokeratosis can lead
      to severe respiratory distress. This report concentrates on the diagnosis and
      successful microsurgical management of laryngeal obstruction in the first female
      case, a 19-month-old girl with pachyonychia congenita.

PMID- 7729989
TI  - Pediatric rhabdomyosarcoma of the head and neck.
AB  - The optimal treatment for most patients with pediatric rhabdomyosarcoma (RMS) of
      the head and neck has been shown to be a combination of surgery, chemotherapy and
      radiation therapy. A retrospective review of patients seen at our institution is
      presented to analyze the impact of multimodality treatment on survival in 32
      pediatric RMS patients. Sixty-five percent (21/32) of the patients were disease
      free at the most recent follow-up. The 5 year disease free survival was 57%
      (17/30). Combined modality treatment in 25 patients consisting of chemotherapy,
      radiation therapy and surgical resection (in 5 patients) rendered 18 (72%)
      patients free of disease. Only 1 of 7 (14%) patients who underwent surgery alone
      as primary management was cured. Two of these 7 patients were salvaged, both with
      combined modality treatment. The Intergroup Rhabdomyosarcoma Study (IRS)
      protocols have resulted in increased survival in pediatric patients with RMS of
      the head and neck. Our results reflect the significant improvement since the IRS
      study was completed.

PMID- 7729990
TI  - Microbiology of chronic suppurative otitis media in children in Surabaya,
      Indonesia.
AB  - The aerobic and anaerobic microbiology of 38 children from Surabaya, Indonesia,
      who suffered from chronic suppurative otitis media (CSOM) was studied using
      strict microbiological methodology. A total of 106 isolates (49 anaerobic and 57
      aerobic) were recovered. Aerobic organisms alone were isolated from 11 (29%),
      anaerobic bacteria only in 4 (11%) and mixed aerobic and anaerobic flora were
      present in 23 (60%). The predominant organisms were Peptostreptococcus sp.,
      Prevotella sp., Bacteroides sp., Staphylococcus aureus, Pseudomonas aeruginosa,
      Klebsiella pneumoniae and Fusobacterium sp. Thirty-nine beta-lactamase-producing
      bacteria were recovered from 22 (58%) patients. These findings demonstrate the
      role of penicillin resistant aerobic and anaerobic bacteria in the polymicrobial
      etiology of CSOM in children from Indonesia. Judicious use of antimicrobial
      therapy may prevent the development of antimicrobial resistance.

PMID- 7729991
TI  - Child preferences for post-tonsillectomy diet.
AB  - Dietary advice for children who have undergone tonsillectomy and adenoidectomy
      (T&A) is divergent. We studied dietary preferences in 2 series of children who
      underwent T&A. The first group of 50 subjects was offered a variety of types of
      food the morning after surgery and they preferred liquids, followed by soft foods
      and were least likely to choose rough foods. When only liquids and soft foods
      were offered to a second group of 50 subjects, less food was wasted compared with
      the first group. A liquid/soft diet enhances food consumption and should continue
      to be advocated to facilitate recovery from T&A after surgery.

PMID- 7729992
TI  - Parotid and submandibular calculi in children.
AB  - Twelve pediatric patients with parotid or submandibular salivary gland calculi
      were successfully diagnosed following appropriately aimed imaging methods. The
      treatment modalities were: secretory stimulation of the gland to induce
      spontaneous passage, sialolithotomy or sialadenectomy. The treatment of choice
      was dependent on the size and location of the calculi, as well as on the affected
      gland and its functional secretory state.

PMID- 7729993
TI  - The indication for tonsillectomy in children following peritonsillar abscess.
AB  - The clinical course of 19 consecutive children treated for peritonsillar abscess
      (PTA), in the Chaim Sheba Medical Center, between 1988-1992 was retrospectively
      reviewed. The abscess was drained through an incision (12 children) and by needle
      aspiration (7 children), under local (11 children) or general (8 children)
      anesthesia. One child suffered from recurrent bouts of tonsillitis after the
      abscess resolved and eventually underwent tonsillectomy. Two others, with a pre
      PTA history of recurrent tonsillitis (T+) underwent interval tonsillectomy.
      Recurrent PTA did not develop in any of the 16 non-operated children. The
      involvement of mainly older children can explain both the low rate of the pre-PTA
      history of T+ and the number of children whose abscess could be drained under
      local anesthesia. Tonsillectomy should be indicated in cases of recurrent PTA or
      in children with a pre-PTA history of T+. The need for general anesthesia for
      draining the abscess in young children does not seem, in itself, to warrant a
      routine hot tonsillectomy.

PMID- 7729994
TI  - Home application of EMLA cream prior to venipuncture. Is it feasible in pediatric
      ENT day care surgery?
AB  - EMLA (Eutectic Mixture of Local Anaesthetics) cream is an emulsion made from
      lidocaine and prilocaine. The cream is well known among parents in Scandinavia,
      and it has become most popular in preventing pain during venipuncture in
      children. To be fully effective the cream must be applied at least 60 min before
      the painful stimulus, which is a major drawback in outpatient practice. Could
      this problem be eliminated by home application of EMLA cream? To answer this we
      performed a study comprising 228 consecutive patients (1-15 years of age) planned
      for outpatient surgery. All parents received a letter with detailed information
      about the procedure and a prescription of EMLA cream. Parents and anaesthesiology
      nurses answered questionnaires after the operation. Twenty-three children were
      excluded from the study due to failure in registration or they were called in to
      fill vacancies. One hundred and eighty out of 205 children had EMLA cream
      applied. Home application of EMLA cream reduced the waiting time at the ENT
      outpatient clinic by at least 60 min, and the study showed that home application
      of EMLA cream is safe, easy to perform and a well-tolerated procedure.

PMID- 7729995
TI  - Point prevalence of type B tympanogram in Riyadh.
AB  - Secretory otitis media (SOM) is primarily a disease of children which can have
      deleterious effect on their medical, social, educational and psychological
      welfare. It is well known that SOM is a common disease, but exact figures about
      its prevalence and incidence are scarce and fragmentary. In this community study,
      we determined the point prevalence of type B tympanogram as an indication to the
      prevalence of SOM. The study population consisted of a random sample of 4214
      children aged 1-8 years. The point prevalence rates of unilateral and bilateral
      type B tympanogram among the children were 5.7% and 8.1%, respectively. The point
      prevalence rate per ears (a total of 8428) was 10.9%. The prevalence was found to
      be related to the age, the season and to the occurrance of the ear and upper
      respiratory tract infections. No correlation was found in relation to sex,
      allergy or the socio-economic condition. The findings are discussed in the light
      of studies conducted elsewhere.

PMID- 7729996
TI  - Therapeutic reintubation for post-intubation laryngotracheal injury in preterm
      infants.
AB  - The failure to extubate a preterm infant after prolonged intubation is often
      caused by laryngotracheal injury. This condition is treated by tracheotomy,
      anterior cricoid split, or often, by reintubation and subsequent extubation
      attempts in a later stage. To assess the value of reintubation as treatment of
      post-intubation injury, we retrospectively studied a group of preterm infants
      from the neonatal intensive care unit in the Sophia Children's Hospital. Three
      categories of injury were distinguished according to the findings at
      laryngobronchoscopy: (a) edema or superficial lesions, (b) ulcerations and edema
      and (c) granulations. Twenty-three infants were therapeutically reintubated after
      post-intubation injury was diagnosed, for a mean period of 17 days. The therapy
      was successful in 22 patients, and a failure in one. The follow-up period was a
      mean 34 months. The result and the duration of the treatment vary with the
      category of the injury and the condition of the patient. Therapeutic reintubation
      is compared with alternatives such as anterior cricoid split and tracheotomy. We
      conclude that reintubation is a valuable therapy that should precede the decision
      for surgery.

PMID- 7729997
TI  - Oral and laryngeal papilloma: a pediatric manifestation of sexually transmitted
      disease?
AB  - Laryngeal and oral papilloma in pediatric patients are generally considered
      transmitted by maternal fetal transmission. In adults and immunocompromised
      patients, it is well documented that human papilloma virus (HPV) of the
      oropharynx is sexually transmitted. The possibility of sexual transmission of
      oral and laryngeal papilloma in children by oral genital contact is discussed.

PMID- 7729998
TI  - Fraser syndrome: a case report and review of the otolaryngologic manifestations.
AB  - Fraser syndrome is a rare autosomal recessive disorder whose major manifestations
      are cryptophthalmos, syndactyly and genital abnormalities. These patients also
      frequently have malformations of the ears, nose and/or larynx. The diagnosis is
      usually made at birth from the obvious malformations, although occasionally made
      on prenatal ultrasound. Treatment is dependent on which malformations are present
      and genetic counseling is indicated. Prognosis is dependent on the severity of
      renal and laryngeal malformations.

PMID- 7729999
TI  - Cleft larynx: repair with a posterior cartilage graft.
AB  - A 4-year-old child presenting with airway obstruction caused by oedema in
      redundant mucosa associated with an Evans Type 2 laryngeal cleft had the cleft
      repaired via a laryngofissure. The defect in the posterior lamina of the cricoid
      cartilage was repaired with a costal cartilage graft to produce a near normal
      post-operative contour to the subglottic lumen.

PMID- 7730000
TI  - An analysis of the results of myringoplasty in children.
AB  - An analysis of the results of 100 temporalis fascia underlay myringoplasties in
      children between the ages of 2-17 years is presented. The follow-up period in
      this retrospective review was from 6 to 24 months. There was no statistically
      significant correlation between the age of patient, a history of previous ear
      surgery, previous general anaesthesia, previous adenotonsillar surgery,
      preoperative otorrhoea, impaired eustachian tubal function, individual surgeon
      performing the surgery, size of perforation or operative technique and the
      outcome of the surgery with respect to graft take rate. The overall graft take
      rate was 75.3% of the 93 patients that returned for follow-up. The seniority of
      the surgeon and by implication the degree of operative experience of the surgeon
      is found to be significantly correlated with the graft take rate (P < 0.05). On
      audiometric testing, the mean pre-operative air conduction threshold improved
      significantly (P < 0.0001) from 32.0 dBHL (S.D. 11.22) to 20.18 dBHL (S.D. 15.54)
      while the speech reception threshold improved from a mean of 25.34 dBHL (S.D.
      12.88) to 18.79 (S.D. 15.5) (P < 0.0005). Although not statistically significant,
      patients under the age of 8 years were found to have a low graft take rate (56%)
      when compared to the mean. The audiometric results in this age group were
      comparable to the rest of the group. The findings in this study suggest that
      myringoplasty is a beneficial procedure in the pediatric population in the hands
      of a skilled and experienced surgeon. The learning curve seen in the surgeons in
      this study suggests that suitable cases for junior surgeons should be carefully
      selected.

PMID- 7730001
TI  - A preliminary survey of nurses' health-related behaviours.
AB  - The substance-use, positive health practices, diet and eating habits, driving
      behaviours and preventive health care practices of 113 nurses living in the
      southeast of England were assessed by means of a postal questionnaire. Females
      were generally more compliant than males with most of the behaviours assessed.
      Females reported taking greater risks with driving behaviours by an occasional
      tendency to "drink and drive". Many males reported both a lack of knowledge of
      how to self-examine their testicles for signs of cancer and little compliance
      with this behaviour. This sample reported more smoking and alcohol use than
      previously reported samples of American nurses and U.K. norms. The nurses in this
      sample were more likely to avoid foods high in cholesterol, add fibre to their
      diet and be more vigilant in their driving behaviour than American nurses and
      British non-nurses.

PMID- 7730002
TI  - Knowledge, beliefs and use of nursing methods in preventing pressure sores in
      Dutch hospitals.
AB  - Different methods have been developed in the past to prevent patients from
      developing pressure sores. The consensus guidelines developed in the Netherlands
      make a distinction between preventive methods useful for all patients, methods
      useful only in individual cases, and methods which are not useful at all. This
      study explores the extent of use of the different methods within Dutch hospitals,
      and the knowledge and beliefs of nurses regarding the usefulness of these
      methods. A mail questionnaire was sent to a representative sample of nurses
      working within Dutch hospitals. A total of 373 questionnaires were returned and
      used for the analyses. The results showed that many methods judged by the
      consensus report as not useful, or only useful in individual cases, are still
      being used. Some methods which are judged as useful, like the use of a risk
      assessment scale, are used on only a few wards. The opinion of nurses regarding
      the usefulness of the methods differ from the guidelines of the consensus
      committee. Although there is agreement about most of the useful methods, there is
      less agreement about the methods which are useful in individual cases or methods
      which are not useful at all. In particular the use of massage and cream are, in
      the opinion of the nurses, useful in individual or in all cases.

PMID- 7730004
TI  - Perceived uncertainty about menopause in women attending an educational program.
AB  - The purpose of this study was to identify predictors of uncertainty among a
      convenience sample of 177 women attending an educational program on menopause and
      to determine whether an educational intervention modified uncertainty. A one
      group pre-test post-test was used. Uncertainty, measured by the Mishel
      Uncertainty in Illness Scale-Community Form (MUIS-C), was relatively high before,
      and decreased significantly after, the program. Findings indicated that
      uncertainty is an important phenomenon associated with menopause. Predictors of
      pre-program uncertainty (T1) were age and perceived level of knowledge. Post
      program uncertainty (T2) was predicted by pre-program uncertainty (T1), perceived
      knowledge gained and level of knowledge at (T2).

PMID- 7730003
TI  - Effectiveness of health instruction provided by student nurses in rural secondary
      schools of Zimbabwe: a feasibility study.
AB  - This demonstration project used student nurses (n = 12) on community deployment
      to provide health instruction among rural school-age populations in Zimbabwe. A
      quasi-experimental (pre- and post-test), non-equivalent control group design was
      used and consisted of 141 school pupils in the intervention group and 144 pupils
      in the comparison group (N = 285). The curriculum focused on prevention of STDs,
      HIV/AIDS and drugs (alcohol, tobacco and marijuana). A gain in health knowledge
      scores among the intervention group was reported at post-test. More than 70% of
      the pupils who received health instruction from student nurses gave a high
      approval rating of student nurses' performance. Further, student nurses, teachers
      and tutors all support school health instruction by student nurses although
      tutors and teachers differ on teaching about condoms.

PMID- 7730005
TI  - The quality of psychiatric nurses' interactions with patients: an observational
      study.
AB  - The behaviour of nursing staff in each ward of a psychiatric hospital was
      observed at 5-min intervals for between 7 and 10 h per day for 10 days. The
      nurses' behaviour was equally divided between interacting with patients,
      interacting with staff, solitary task oriented behaviour and other behaviours.
      There was less staff-patient interaction in the acute ward than in the long-term
      and psychogeriatric wards and senior nurses interacted less with patients and
      engaged in more solitary task oriented behaviour. Of the interactions with
      patients, almost 25% were rated as positive and only 0.3% negative. In the long
      term wards almost 47% of the interactions were positive.

PMID- 7730006
TI  - Towards knowledge-based practice; an evaluation of a method of dissemination.
AB  - This paper describes a method for the dissemination of research-based information
      to nurses. The approach involved the development and evaluation of a clinical
      information pack relating to the management of leg ulcers. The evaluation
      incorporated a pre-post test two group experimental design. The sample comprised
      171 qualified community nurses working in five health authorities. Data were
      collected by means of two extensive questionnaires administered to groups of
      nurses. The study collected large amounts of descriptive data pertaining to
      nurses' clinical practices in the care of this patient group. It also uncovered
      important factors, quite independent of leg ulcers, related to relationship
      between research and clinical practice, and the way information is disseminated
      to practitioners. These independent findings and their implications are discussed
      here.

PMID- 7730007
TI  - When the severely ill elderly patient refuses food. Ethical reasoning among
      nurses.
AB  - Forty registered nurses (RNs) regarded as "good and experienced" in either cancer
      or dementia care, were asked about their decision to feed or not feed a severely
      ill elderly woman (a hypothetical case). In order to compare ethical reasoning in
      the two groups of nurses and to illuminate what it means to RNs to face a
      situation where the patients can/cannot decide for themselves, a phenomenological
      hermeneutic approach was used for the analysis. Both groups saw themselves as the
      advocate for their patients but in different ways. The RNs who talked about a
      mentally alert patient emphasized that they encouraged their patient to speak up
      for herself, while the RNs who talked about a severely demented patient
      emphasized that they tried very hard to interpret their patient's vague and
      unclear communicative cues and to act as her advocate, especially in relation to
      physicians. Transcending experiences of dying relatives and patients as well as
      role models helped them to achieve their ambition of putting themselves in the
      patient's shoes in order to respect and understand her or his wish and/or what
      was best for them. The majority of RNs strongly rejected active euthanasia.

PMID- 7730008
TI  - The evaluation of a nursing model for long-stay psychiatric patient care. Part 1-
      Literature review and methodology.
AB  - A modified action research approach was used to implement a selected nursing
      model on a long-stay psychiatric ward. Within a broader quasi-experimental
      design, specific quality of care indicators were appraised before and after the
      implementation of the model. These dependent variables were also monitored on a
      control ward and data were collected on both wards at one pre-test and two post
      test points. This paper presents a comprehensive overview of the literature and
      the methodology for the study. Planned change theory was used as a guiding
      framework for the implementation of the model and this process is described in
      detail.

PMID- 7730009
TI  - The evaluation of a nursing model for long-stay psychiatric patient care. Part 2-
      Presentation and discussion of findings.
AB  - A nursing model selected by a population of ward managers was implemented on a
      long-stay psychiatric ward in Northern Ireland using an adapted action research
      approach within a quasi-experimental design. A range of dependent variables were
      appraised at one pre-test and two post-test evaluation points on an experimental
      (Ward X) and a control ward (Ward Y). A thorough review of the literature and
      methods used can be found in Part 1 (McKenna et al., 1995, Int. J. Nurs. Stud.,
      32, 79-94). The findings and their interpretations are presented here. Results
      indicate that on the experimental ward there were statistically significant
      improvements in "Psychiatric Monitor", patients' and staff's perception of ward
      atmosphere, patient satisfaction, staff's views about nursing models, and patient
      dependency levels. No significant changes were noted in nurse satisfaction levels
      nor nurses' perception of patients' behaviour. Particular emphasis is placed on
      the possible threats to the internal and external reliability of these findings
      and on the attempts made to control these threats.

PMID- 7730010
TI  - Docosahexaenoic acid in red blood cells of patients with X-linked retinitis
      pigmentosa.
AB  - PURPOSE: Abnormalities in the distribution of long-chain polyunsaturated fatty
      acids (LCPUFA) have been documented in plasma of patients with X-linked retinitis
      pigmentosa (XLRP). In this study, fatty acid profiles of red blood cells (RBC)
      were used as an index for LCPUFA metabolism in patients with XLRP because RBC
      lipids reflect membrane-associated fatty acids. Correlations between LCPUFA
      content and electroretinographic (ERG) function were assessed. METHODS: Mean ages
      for the XLRP group (n = 18) and control group (n = 28) were 22 +/- 18 years and
      24 +/- 16 years, respectively. Electroretinographic assessment included the
      International Society for the Clinical Electrophysiology of Vision standard
      protocol. Methyl esters of RBC fatty acids were analyzed by capillary column gas
      chromatography. RESULTS: The content of the omega 3 fatty acid, docosahexaenoic
      acid (DHA), was 40% lower in the group with XLRP (23.1 +/- 5.9 micrograms/ml RBC
      [mean +/- 1 SD]) than in normal subjects (38.6 +/- 9.4 micrograms/ml RBC, t =
      6.24, P < 0.0001). Total omega 3 LCPUFA content in patients with XLRP was reduced
      by 30% from normal levels compared to a 10% reduction in omega 6 LCPUFA levels.
      Elongation reactions for omega 3, omega 6, saturated fatty acids, and
      monounsaturated fatty acids were markedly lower for patients with XLRP than for
      normal subjects. Multiple regression analysis revealed that RBC-DHA was a
      significant determinant for amplitude and implicit time of cone ERG responses.
      CONCLUSIONS: The overwhelming majority of patients with XLRP have lower levels of
      DHA in RBCs compared to normally sighted control subjects. An analysis of fatty
      acid profiles suggests a metabolic defect in fatty acid chain elongation
      mechanisms. The significant association between DHA content and cone ERG response
      parameters is consistent with an effect of lipid abnormalities on membrane
      environment and physiology in retinal photoreceptors.

PMID- 7730011
TI  - The effects of acetazolamide on the electroretinographic responses in rats.
AB  - PURPOSE: To study the mechanisms and sites of action of the carbonic anhydrase
      inhibitor, acetazolamide (AZM), on the rod- and cone-mediated electroretinogram
      (ERG) of the dark-adapted rat. METHODS: After a within-subjects design, ERG
      responses to brief, full-field flashes were recorded from adult (60 to 90 days
      old) albino rats, with and without AZM (5 mg/100 g, intraperitoneally).
      Flickering stimuli (6 and 26 Hz) were used to study rod- and cone-mediated
      responses. Aspartate-isolated responses of the isolated retina were recorded with
      and without AZM in the superfusate. The a-wave and PIII responses were fitted
      with a model of the rod's response by estimating the maximum response (Rmp3),
      sensitivity (S), and delay td. The b-wave response amplitude and implicit time
      were examined as a function of stimulus energy. The parameters obtained in the
      AZM-treated and untreated conditions were compared. RESULTS: Acetazolamide causes
      a significant decrease in saturated rod response, b-wave amplitude, aspartate
      isolated PIII, and the rod- and cone-mediated responses to flickering light. The
      estimated sensitivity of the rod response (S), b-wave sensitivity, and b-wave
      implicit time are not altered significantly by AZM. CONCLUSION: Acetazolamide,
      probably through mechanisms that acidify the retina, attenuates the amplitudes of
      the retinal responses without significant effect on sensitivity.

PMID- 7730012
TI  - Rod phototransduction in retinitis pigmentosa. Distinguishing alternative
      mechanisms of degeneration.
AB  - PURPOSE: To test alternative hypotheses concerning the mechanisms of rod
      degeneration in retinitis pigmentosa (RP). METHODS: Full-field rod
      electroretinograms and rod visual fields were measured for 15 patients with RP
      and a normal control group. The rod a-wave was fitted with a computational model
      based on known transduction biochemistry. The values of td (the initial delay), S
      (a sensitivity parameter), and RmP3 (the maximum amplitude) were estimated. Rod b
      wave amplitudes were fitted with the Michaelis-Menten equation, and the
      parameters Kbw (the semisaturation intensity--a sensitivity parameter) and Vmax
      (the maximum amplitude) were estimated. RESULTS: The patients all had
      significantly reduced values of RmP3, indicating rod receptor damage, and a wide
      range of S values. Three patients had S values in the normal range. Four had
      abnormal S values but normal thresholds in some locations in their visual field.
      The remaining patients had abnormal values of S and entirely abnormal visual
      fields. Three of those had a history of large elevations in Kbw. For all
      patients, the changes in Kbw and Vmax followed closely the changes in S and RmP3,
      respectively. CONCLUSION: Retinitis pigmentosa has a varying initial impact on
      the activation phase of rod transduction. Available evidence suggests that the
      activation of transduction is initially normal in most patients with RP. In some
      patients, RP appears to result in a reduced transduction amplification from
      birth. In all patients, subsequent degeneration of the rods effects progressive
      reductions in transduction amplification but no other major functional changes.
      Outer segment shortening and local dropout of rods appear to have little
      functional impact.

PMID- 7730013
TI  - The development of the rod photoresponse from dark-adapted rats.
AB  - PURPOSE: To study electroretinographic a- and b-wave responses of rats at the
      ages during which rod outer segment length (ROS) and rhodopsin content increase.
      METHODS: Electroretinographic responses to brief, full-field stimuli were
      recorded from dark-adapted young (ages 12 to 30 days) and adult rats. The
      amplitude of the a-wave and the amplitude and implicit time of the b-wave were
      examined as a function of stimulus intensity. Sensitivity (S), saturated
      amplitude (RmP3), and delay (td) of the rod cell responses were calculated from
      the a-waves. RESULTS: The developmental increase in saturated a-wave amplitude
      parallels, but lags behind, growth of outer segment length, whereas the saturated
      b-wave amplitude increases with about the same course as rhodopsin content of the
      retina. The sensitivity, S, depends on rhodopsin content, and the developmental
      decrease in the flash energy required to produce a half-maximum b-wave amplitude
      is inversely proportional to the developmental increase in rhodopsin content. No
      significant age-dependent variation in td can be detected. CONCLUSION: During
      development, ROS length and rhodopsin content of the retina are significant
      determinants of a- and b-wave response parameters.

PMID- 7730014
TI  - Ethambutol alters spinule-type synaptic connections and induces morphologic
      alterations in the cone pedicles of the fish retina.
AB  - PURPOSE: Ethambutol can cause optic neuropathy and deficiencies in color-opponent
      visual processing in patients treated for tuberculosis. In fish, Ethambutol
      induces color vision deficiencies similar to those observed in humans and affects
      color coding in retinal ganglion cells. Color opponency in fish is mainly
      mediated by a horizontal cell feedback onto cones thought to be provided by
      spinules. The authors examined whether Ethambutol affects spinules and is,
      therefore, able to alter color processing at a distal stage, that is, at the
      first synaptic connection within the retina. METHODS: Ethambutol was injected
      into the vitreous of either dark- or light-adapted fish. After drug application,
      fish were held under different illumination conditions. Thereafter, the retinas
      were dissected and prepared for electron microscopy. Ultrathin tangential
      sections of retinas were examined at the level of the outer plexiform layer.
      RESULTS: In already light-adapted retinas, a high dose of Ethambutol (10 mM)
      reduced the number of spinules by 30%. Ethambutol application in the dark with
      subsequent light adaptation resulted in severe dose-related inhibition of light
      induced spinule formation. In these experiments, low doses (0.1 mM) of Ethambutol
      caused 40% inhibition, and high doses (10 mM) caused 70% inhibition. Besides
      affecting spinules, Ethambutol occasionally induced a degeneration of cone
      pedicles. This neurotoxicity only occurred in cones exposed to light.
      CONCLUSIONS: Results show that Ethambutol alters synaptic connections between
      horizontal cells and cones in a dose-related fashion; Ethambutol treatment can be
      toxic for cone pedicles and can cause their degeneration; and the rod pathway is
      not affected by the drug. This indicates that Ethambutol influences the color
      coding process already at the level of the cone-horizontal cell synapse.

PMID- 7730015
TI  - Experimental autoimmune anterior uveitis. Induction with melanin-associated
      antigen from the iris and ciliary body.
AB  - PURPOSE: This study was designed to investigate an animal model of uveitis that
      resembles anterior uveitis in humans after immunization with iris-ciliary body
      antigen. METHODS: Male Lewis rats 6 to 8 weeks of age were immunized with the
      buffer- and detergent-insoluble bovine iris-ciliary body antigen mixed with
      complete Freund's adjuvant and pertussis toxin. Antigen was digested with various
      proteolytic enzymes and tested in different rodent strains for a uveitogenic
      response. RESULTS: Acute iridocyclitis developed in both eyes of the Lewis rat
      during the second week after immunization, and the pattern of inflammation was
      similar to acute anterior uveitis in humans, with sudden onset, localization to
      the anterior uvea, and spontaneous resolution. Among the strains tested, F344
      rats were susceptible to experimental autoimmune anterior uveitis but Long-Evans
      rats were not. Experimental autoimmune anterior uveitis did not develop in any of
      the mice studied, nor was it induced by immunization with synthetic melanin,
      amelanotic bovine tissues, pigmented bovine skin, or pigmented rat and rabbit
      iris-ciliary body. A soluble fraction derived from bovine melanin-associated
      antigen (BMAA) after digestion with the proteolytic enzyme V8 protease resulted
      in a disease similar to that observed with intact BMAA. CONCLUSIONS: A model of
      anterior uveitis has been induced in the Lewis rat after immunization with bovine
      uveal antigen, and it resembles the acute iridocyclitis observed in humans. These
      results suggest that the pathogenic antigen is a melanin-associated protein(s)
      present within the iris-ciliary body.

PMID- 7730016
TI  - Efficacy of tumor-infiltrating lymphocytes in the treatment of hepatic metastases
      arising from transgenic intraocular tumors in mice.
AB  - PURPOSE: The purpose of this study was to determined if tumor-infiltrating
      lymphocytes (TIL) isolated from transgenic intraocular tumors were capable of
      preventing the development of spontaneous hepatic metastases. METHODS: Tumor
      infiltrating lymphocytes were isolated from intraocular tumors in immunocompetent
      mice and were examined for cytolytic activity in vitro. The antigenic phenotypes
      of the TIL were determined by in situ immunohistology. Cultured TIL were
      transferred adoptively to immunoincompetent, intraocular, tumor-bearing
      recipients to determine the efficacy of TIL in preventing spontaneous liver
      metastases. RESULTS: Cultured TIL displayed remarkable cytolytic activity in
      vitro and antimetastatic properties after adoptive transfer into
      immunoincompetent, athymic nude mice and anti-CD4/CD8-treated euthymic FVB/N
      mice. Hepatic metastases developed in only 2 of 10 athymic nude mice that
      subsequently received TIL, whereas metastases developed in all 10 control mice.
      Similar results were found in anti-CD4/CD8-treated FVB/N mice. Hepatic metastases
      did not develop in any of the 10 mice treated with TIL, whereas extensive
      metastatic foci developed in all 10 untreated FVB/N control mice. The efficacy of
      TIL therapy was manifested also by significant prolongation of host survival
      times. CONCLUSIONS: Tumor-infiltrating lymphocytes isolated from intraocular
      tumors can be expanded in vitro and can exert antimetastatic effects in vivo.

PMID- 7730017
TI  - Modification of vitamin E during ischemia-reperfusion in rat retina.
AB  - PURPOSE: To determine the variations of vitamin E in rat retinas after transient
      ischemia and reperfusion. METHODS: Male Wistar rats 11 to 12 weeks of age were
      used in all experiments. Ischemia was induced by ligation of the optic nerve and
      vessels, then reperfusion was obtained by removing the ligature. Retinas were
      dissected, and vitamin E was analyzed by a modified high-performance liquid
      chromatography assay. RESULTS: There was an insignificant rise in vitamin E
      during ischemia and a dramatic decrease after reperfusion. No changes were
      dependent on the period of ischemia (30, 60, or 90 minutes) or reperfusion (15 or
      120 minutes). CONCLUSION: Vitamin E decreased only in the reperfused groups,
      demonstrating a depletion of defenses against free radical production occurring
      during reperfusion. Vitamin E changes may represent an indirect measure of
      lipoperoxidation during ischemia-reperfusion and, thus, a potential parameter to
      evaluate drugs in vitro.

PMID- 7730018
TI  - Characterization of endothelin A (ETA) and endothelin B (ETB) receptors in
      cultured bovine retinal pericytes.
AB  - PURPOSE: The endothelins are a family of structurally similar vasoactive
      peptides. It has been shown recently that cultured retinal microvascular
      endothelial cells secrete endothelin-1 (ET-1) and that corresponding pericytes
      bear receptors and are responsive to this peptide. These findings suggest a role
      for ET-1 in the autoregulation of retinal blood flow. There are at least two
      known subtypes of ET receptors, ETA and ETB. The purpose of this study was to
      characterize endothelin receptor subtypes on cultured bovine retinal pericytes
      (BRP). METHODS: To characterize the specific binding sites for ET-1 and ET-3 on
      monolayers of BRP, a radioligand binding assay was performed using [125I] ET-1
      and [125I] ET-3. Competition binding studies with ET-1 and ET-3 were used to
      assess the heterogeneity of the ET-receptor population on BRP. Also, [125I] ET-1
      and ET-3 were covalently linked to their corresponding receptors and analyzed on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by
      autoradiography. RESULTS: [125I] ET-1 and [125I] ET-3 showed specific binding to
      BRP and subsequent Scatchard analysis for both labels showed upward concavity,
      implying two-site ligand binding. Unlabeled ET-1 was found to displace [125I] ET
      1 with greater efficiency than ET-3, indicating the presence of the ETA receptor
      subtype. Conversely, [125I] ET-3 was displaced by ET-1 and ET-3 with equal
      potency, indicating a component of ETB in the receptor population. Preincubation
      with BQ123, an ETA selective antagonist, decreased the binding of [125I] ET-1 but
      had no effect on [125I] ET-3 binding curves. Affinity cross-linking of the
      receptors showed two distinct protein bands on SDS-PAGE of 66 and 45 kd,
      corresponding to ETA and ETB. CONCLUSIONS: These results show that BRP possess
      ETA and ETB receptor subtypes. The function of ETB on BRP may be to modulate the
      vasoconstrictive effect of ET-1 caused through ETA.

PMID- 7730019
TI  - Loss of keratocyte ion channels during wound healing in the rabbit cornea.
AB  - PURPOSE: Corneal keratocytes are responsible for repairing the corneal stromal
      matrix after injury or infection. Recent work has characterized the primary
      voltage-gated ion currents in keratocytes from normal, uninjured corneas. The
      purpose of the present study was to examine and characterize keratocyte voltage
      gated ion currents from freeze-wounded rabbit corneas. METHODS: Rabbit corneas
      were injured using a liquid nitrogen cooled brass probe. Keratocytes were
      isolated from control eyes, trephined buttons of stroma encompassing the wound
      area, and the stromal rim surrounding the button. Ionic currents were examined
      using the amphotericin perforated-patch variation of the whole cell patch clamp
      technique. RESULTS: The delayed rectifier K+ current, described previously as the
      primary voltage-gated outward current in keratocytes, was found in 100% of
      control cells, 91% of cells isolated from the corneal rim of wounded cells, and
      33% of cells isolated from the wound region. Na+ currents were also seen with a
      lower frequency in cells from the wound area. CONCLUSION: The majority of
      keratocytes migrating into a corneal freeze wound lose the voltage-gated K+ and
      Na+ ion channels present in cells from normal corneas. Ion channels from cells
      surrounding the wound site are minimally affected by the injury.

PMID- 7730020
TI  - Aged mice fail to upregulate ICAM-1 after Pseudomonas aeruginosa corneal
      infection.
AB  - PURPOSE: In young Swiss (HSD:ICR) outbred mice, corneal clarity is restored after
      Pseudomonas aeruginosa ocular infection, whereas disease in aged outbred mice
      progresses to corneal perforation. This study was conducted to elucidate further
      the mechanism responsible for this age-related disparity in disease response.
      METHODS: Corneas of young (6 to 8 weeks of age) and aged (1.5 to 2 years) female
      mice were scarified and inoculated with 1.0 x 10(8) colony-forming units of P.
      aeruginosa ATCC 19660. Eyes were scored for corneal pathology (0 to +4) at 6, 12,
      24, 48, 72, 96, and 120 hours after infection. At each time point, six mice were
      killed from each age group, and both eyes were enucleated. Eyes (three infected,
      three uninfected) were embedded in OCT compound, frozen in liquid nitrogen,
      sectioned on a cryostat, and stained for ICAM-1 and LFA-1 immunoreactivity. The
      remaining six eyes (three infected, three uninfected) were embedded in
      eponaraldite resin, thick sectioned, and stained for light microscopic
      histopathologic examination. RESULTS: Immunostaining of slight to moderate
      intensity for ICAM-1 was seen on conjunctival fibroblasts, stromal keratocytes,
      corneal epithelium, and endothelium and conjunctival blood vessel endothelium of
      uninfected contralateral eyes in both age groups. In response to P. aeruginosa
      infection, only young animals were capable of upregulating ICAM-1 (as evidenced
      by an increase in the intensity of immunostaining) on these cells when compared
      to aged mice. Conversely, the intensity of immunostaining for LFA-1, a ligand for
      ICAM-1 on infiltrating leukocytes, was similar despite animal age. On gross
      observation, corneal pathology was more severe in young mice 24 to 96 hours after
      infection. Histopathologically, in contrast to young mice, eyes of aged animals
      24 to 48 hours after infection had significantly fewer inflammatory cells, such
      as polymorphonuclear leukocytes (PMNs), infiltrating the corneal stroma and
      adhering to the endothelium near wound sites. CONCLUSION: These data suggest that
      the disparate response to ocular P. aeruginosa infection in young versus aged
      mice is due, at least in part, to the inability of aged animals to upregulate
      ICAM-1 above constitutively expressed levels. Consequently, the migration of
      inflammatory cells (PMNs) into infected corneas of aged mice is delayed, perhaps
      facilitating bacterial growth and contributing to a poor prognosis.

PMID- 7730021
TI  - The spatial organization of corneal endothelial cytoskeletal proteins and their
      relationship to the apical junctional complex.
AB  - PURPOSE: To determine the spatial organization of the major cytoskeletal proteins
      and their relationship to the apical junctional complex (AJC) in the normal
      rabbit corneal endothelium. METHODS: Normal endothelial cytoskeletal structure in
      three dimensions was studied in rabbit eyes by laser scanning confocal microscopy
      after en bloc immunocytochemical staining of whole corneal tissue with various
      antibodies and fluorescent probes; specificity of antibodies to rabbit corneal
      endothelial cell proteins was established by Western blot analysis. RESULTS:
      Normal actin microfilament network organization was seen predominantly as a
      complex apical array forming a circumferential bundle. The tight junction
      associated protein ZO-1 was positive at the apical junctions, forming a hexagonal
      pattern that was localized between and just proximal to the circumferential actin
      microfilament bundles. The distribution of ZO-1 was discontinuous around the
      cell, with the largest gaps (1 micron in diameter) occurring at the Y-junction
      between adjacent endothelial cells; transmission electron microscopy of the
      apical face of the endothelium confirmed the existence of 1-micron diameter gaps
      in the adherens junctions located at the Y-junction. Antivimentin antibodies
      showed a ring of intermediate filaments located just below the circumferential
      actin microfilament band. This ring appeared to be continuous with a basal mat of
      filaments, which together formed a basketlike structure within endothelial cells.
      An intricate cytoplasmic, perinuclear network of microtubules was observed by
      antitubulin antibodies that appeared unrelated either to the apical
      circumferential actin microfilament bundle or to intermediate vimentin filament
      ring. Staining of endothelial cells with NBD-ceramide identified a prominent,
      perinuclear Golgi complex suggesting an association between microtubules and
      Golgi. CONCLUSIONS: The organization of cytoskeletal elements and the tight
      junction-associated protein ZO-1 is similar to the classical AJC of transporting
      epithelia, comprised of a zonulae occludens (ZO) located apical to a zonulae
      adherens (ZA) and desmosomes. The organizational pattern seen in corneal
      endothelial cells, however, is distinct from transporting epithelia in that the
      ZO and ZA are discontinuous, with large gaps in the ZO-1 distribution at the Y
      junction between adjacent endothelial cells. The authors propose that the
      structural differences in the AJC underlie the functional differences between
      classical transporting epithelia, which actively pump fluid from the lumen to the
      mucosa, and the corneal endothelium, which has a "pump-leak" fluid transport
      mechanism.

PMID- 7730022
TI  - Evidence for fibromuscular pulleys of the recti extraocular muscles.
AB  - PURPOSE: Magnetic resonance imaging (MRI) shows that the paths of recti
      extraocular muscle (EOM) bellies remain fixed in the orbit during large ocular
      rotations and across large surgical transpositions of their insertions. These
      findings imply that recti EOMs pass through pulleys coupled to the orbit and
      anterior to the muscle bellies, because the insertions must move with the globe.
      The present study was conducted to locate anatomically and to characterize
      histologically the pulley tissues. METHODS: High-resolution MRI images were
      collected from volunteers, using multiple gaze directions to infer the locations
      of, and occasionally to visualize, recti EOM pulleys. Fresh cadaver orbits were
      exenterated and dissected to evaluate mechanical and structural properties of the
      orbital connective tissues. Lipid was cleared from whole specimens to reveal
      tissue relationships. Other specimens were selectively step- and serial-sectioned
      for histochemical and immunohistochemical staining. RESULTS: Magnetic resonance
      imaging demonstrated dense connective tissue structures within posterior Tenon's
      fascia near the equator of the globe adjacent to the recti EOMs. Histochemistry
      showed these structures to be pulleys--fibroelastic EOM sleeves consisting of
      dense bands of collagen and elastin, suspended from the orbit and adjacent EOM
      sleeves by bands of similar composition. A monoclonal antibody to human smooth
      muscle alpha-actin demonstrated substantial smooth muscle in the pulley
      suspensions and in posterior Tenon's fascia. Tenon's fascia itself was seen to be
      suspended at its periphery from the orbital walls like a drumhead. CONCLUSIONS:
      The human orbit contains specialized musculofibroelastic tissues in and just
      posterior to Tenon's fascia that serve as compliant pulleys and determine the
      pulling directions of recti EOMs. In this sense, the pulleys are the functional
      origins of the recti EOMs and are determinants of ocular motility.

PMID- 7730023
TI  - Differential regulation of a glial fibrillary acidic protein-LacZ transgene in
      retinal astrocytes and Muller cells.
AB  - PURPOSE: Glial fibrillary acidic protein (GFAP) is normally expressed in
      astrocytes, but not in Muller cells, in the mouse retina. In response to retinal
      injury or photoreceptor degeneration, however, GFAP gene transcription is
      strongly activated in the Muller cell. To identify the genetic elements involved
      in GFAP gene induction, the authors have studied gene expression in transgenic
      mice in which beta-galactosidase (beta-gal) expression is under control of GFAP
      regulatory sequences. METHODS: Histochemical methods were used to study gene
      expression. The transgene expression was followed by x-gal staining, whereas GFAP
      expression was monitored by immunostaining with GFAP antibody. RESULTS: In GFAP
      LacZ transgenic mice, beta-gal activity and GFAP immunostaining were found in
      retinal astrocytes. Transgene expression showed the same developmental pattern as
      that of endogenous GFAP in retinal astrocytes. In addition, beta-gal staining
      also was observed in lens epithelial cells. Neither GFAP nor beta-gal expression
      was seen in Muller cells in the adult or developing retina. When focal retinal
      lesions were introduced into the retina, strong GFAP immunostaining was observed
      in Muller cells throughout the retina. No beta-gal staining was seen in Muller
      cells in these retinas. In astrocytes, however, beta-gal and GFAP both were
      present. CONCLUSIONS: The observations suggest that cis elements responsible for
      GFAP expression in retinal astrocytes are present in 5' flanking region of the
      GFAP gene, whereas the regulatory elements involved in GFAP induction in Muller
      cells are located elsewhere.

PMID- 7730024
TI  - Assessment of retinal-neural function before neodymium:YAG laser capsulotomy.
AB  - PURPOSE: The aim of this study was to evaluate a clinical test of hyperacuity in
      the assessment of retinal-neural function in patients with posterior capsular
      opacification. METHODS: Neodymium (Nd):YAG laser capsulotomy was performed on 39
      subjects (mean age, 76.72 years +/- 10.41 years). Measurements of refractive
      error, logMAR acuity, and displacement threshold hyperacuity (DTH) were made
      before and 3 weeks after Nd:YAG therapy. The DTH task involved measurement of the
      smallest detectable displacement of an object relative to two stationary
      references. In addition, an independent fundus examination was performed before
      and after therapy to determine the presence of retinal disease. By
      ophthalmoscopic examination, a blind protocol was adopted for the classification
      of subjects as normal or as having retinal disease. RESULTS: Preoperative
      measures of logMAR visual acuity were of no value in distinguishing between
      patients with retinal disease and normals (P > 0.1) and were a poor indicator of
      postoperative logMAR acuity (r2 = 0.2). Preoperative DTH could be used to
      distinguish patients with retinal disease from normals (P < 0.005) and were found
      to be correlated with measures of postoperative logMAR acuity (r2 = 0.4).
      Preoperative DTH correlated well with postoperative DTH (r2 = 0.7), which is
      consistent with its resistance to optical image degradation. CONCLUSION: The
      results of this study indicate that DTH is of value in the presurgical assessment
      of visual function in patients with media opacification if adequate fundus
      examination is not possible.

PMID- 7730025
TI  - The influence of cerebrospinal fluid pressure on the lamina cribrosa tissue
      pressure gradient.
AB  - PURPOSE: To measure the tissue pressure gradient through the optic disk and to
      determine the relationship between intraocular, cerebrospinal fluid, and
      retrolaminar tissue pressures. The relationship of optic nerve subarachnoid space
      pressure to intracranial cerebrospinal fluid pressure also was explored. METHODS:
      Micropipettes coupled to a pressure transducer were passed through pars plana and
      vitreous to enter the optic disk in the anesthetized dog. Using a
      micromanipulator, pipettes penetrated the optic disk in steps while pressure
      measurements were taken. In some animals, pipettes also were passed into the
      optic nerve subarachnoid space. Lateral ventricle cerebrospinal fluid pressure,
      intraocular pressure, and arterial blood pressure were measured concurrently, and
      the effect of raising CSF pressure was explored. RESULTS: Retrolaminar tissue
      pressure was largely dependent on the surrounding cerebrospinal fluid pressure,
      which was on average 8.6 +/- 3.5 mm Hg (SD, n = 8) higher, and was independent of
      intraocular pressure. Most (85% +/- 15% [SD, n = 8]) of the pressure drop between
      intraocular pressure and retrolaminar pressure occurred across the anterior 400
      microns of disk tissue. When the intraocular pressure was 21 mm Hg and the
      cerebrospinal fluid pressure was zero, retrolaminar tissue pressure averaged 7 mm
      Hg and the translaminar pressure gradient was 3.08 +/- 0.29 mm Hg/100 microns
      tissue (SD, n = 3). Optic nerve subarachnoid space pressure was equivalent to
      lateral ventricular pressure. CONCLUSIONS: These results show that cerebrospinal
      fluid pressure largely determines retrolaminar tissue pressure; hence, along with
      intraocular pressure, it is of major importance in setting the translaminar
      tissue pressure gradient. Results also demonstrate hydrostatic continuity between
      the optic nerve subarachnoid space and the lateral ventricle. That the
      translaminar pressure gradient can vary independently of intraocular pressure may
      be of importance in understanding the pathophysiology of glaucoma.

PMID- 7730026
TI  - Identification of G proteins in lacrimal gland.
AB  - PURPOSE: The intent of this study was to identify and characterize guanine
      nucleotide binding proteins (G proteins) that are a component of cell signaling
      of stimulus-secretion coupling in lacrimal gland. METHODS: Membranes were
      isolated from the lacrimal glands of male Sprague-Dawley rats and New Zealand
      rabbits and were used to identify G proteins in lacrimal gland by Western blot
      analysis. Solubilized membrane proteins from lacrimal glands and from a positive
      tissue control (SH-SY5Y cells) were separated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The alpha subunits of the G proteins were
      identified by immunoreactivity, with specific peptide directed antisera against
      Gs alpha, Gi alpha 1, Gi alpha 1/2, and Go alpha. The initial characterization of
      coupling of specific G proteins to receptors was accomplished by preincubation of
      membranes with nonimmune serum, anti-Gs alpha, or anti-Go alpha antiserum and
      assay of adenylyl cyclase activity in the presence of the neuropeptide,
      vasoactive intestinal peptide (VIP), or forskolin. RESULTS: Gs alpha, Gi alpha 3,
      and Go alpha were present in all three membrane preparations. Gs alpha subunits
      were detected as two bands at 45 to 48 kd and 48 to 54 kd. Gi alpha 3 was
      detected as a single protein at 40 to 41 kd, and at least one form of Go alpha
      with a molecular weight of 40 kd was detected in all three preparations. Gi alpha
      1 was detected in immunoblots of rat lacrimal and SH-SY5Y membranes at 41 kd, and
      the density of the band was enhanced in blots probed with anti-Gi alpha 1/2
      antiserum. Immunoreactivity to anti-Gi alpha 1 or anti-Gi alpha 1/2 was faint or
      not detectable in rabbit lacrimal membranes. A prominent band was detected in
      rabbit and rat lacrimal but not in SH-SY5Y membranes at 31 kd with anti-Gi alpha
      1/2 antiserum, which may represent a G protein involved in exocytosis. Coupling
      of VIP receptor activation to adenylyl cyclase by Gs alpha was evidenced by the
      reduction of VIP stimulation of the enzyme by preincubation of rabbit membranes
      with anti-Gs alpha antiserum. In contrast, preincubation of membranes with anti
      Go alpha antiserum resulted in an increase in activity of adenylyl cyclase in the
      presence of VIP. CONCLUSIONS: Detection of specific alpha subunits in lacrimal
      gland indicates that Gs, Gi, and Go are present in rabbit and rat lacrimal gland.
      Both Gs and Go influence VIP stimulation of lacrimal adenylyl cyclase and thus
      are presumed to be involved in signal transduction, leading to second-messenger
      accumulation and subsequent regulation of lacriminal function, including
      secretion. In addition, an unidentified protein is present in lacrimal gland that
      may represent one of the guanine nucleotide binding proteins involved in
      exocytosis.

PMID- 7730027
TI  - Cold stress-induced recurrences of herpetic keratitis in the squirrel monkey.
AB  - PURPOSE: Models of recurrent herpetic keratitis that depend on tissue damage or
      immunosuppression have been described. The authors report a model that depends
      only on minimal temperature stress to produce clinical recurrences in a small
      primate. METHODS: Squirrel monkeys (Saimiri sciureus) infected by the ocular
      route with the Rodanus strain of herpesvirus type 1 (HSV-1) were exposed to
      temperatures approximately 5 degrees C lower than the usual ambient temperature
      for periods as short as 12 hours. RESULTS: The corneas showed more or larger
      lesions typical of recurrent herpetic keratitis than are usually seen in these
      animals under normal conditions. Statistical analysis showed that there were
      significantly higher frequencies of epithelial keratitis at 18 degrees C and 20
      degrees C (P < 0.0001). CONCLUSIONS: A minimal temperature change produced
      significant recurrences in this small animal within a short time. Tissues were
      not damaged to produce the recurrences. This approach may provide an efficient
      primate model for rapid testing of drugs to prevent clinical recurrence of ocular
      herpetic keratitis.

PMID- 7730028
TI  - Expression of bFGF and TGF-beta 2 in experimental myopia in chicks.
AB  - PURPOSE: To determine factors that control ocular enlargement in experimental
      form-deprivation myopia and to clarify the mechanism of form-deprivation myopia.
      METHODS: After the left eyes of 20 chicks were monocularly occluded for 2 weeks,
      protein, basic fibroblast growth factor (bFGF) and transforming growth factor
      (TGF)-beta 2 contents in samples of constant area (circular button, diameter =
      8.5 mm) in the retina-retinal pigment epithelium (RPE)-choroid and the sclera in
      the posterior region of control and myopic eyes were determined by enzyme-linked
      immunosorbent assay. RESULTS: The bFGF content (per circular button) and bFGF
      concentration (per mg protein) were significantly lower in the sclera in the
      posterior region of the myopic eyes than in control eyes. The bFGF content and
      concentration were similar in the retina-RPE-choroid in myopic and control eyes.
      The TGF-beta 2 content and concentration were significantly higher in myopic eyes
      in both the retina-RPE-choroid and the sclera (P < 0.05). CONCLUSIONS: These
      results are consistent with the possibility that bFGF and TGF-beta 2 regulate
      ocular enlargement or respond to myopiagenic mechanisms in form-deprivation
      myopia.

PMID- 7730029
TI  - Characterization of ciliary muscle relaxation induced by various agents in cats.
AB  - PURPOSE: To understand the cellular mechanism underlying the relaxation of
      ciliary muscle, relaxation induced by prostaglandins (PGs) and some other agents
      was characterized in the cat. METHODS: Tone of isolated ciliary muscle was
      measured by means of a force-displacement transducer. Adenylate cyclase activity
      was determined with membrane fraction of ciliary muscle by measuring the
      formation of cyclic adenosine monophosphate (cAMP). RESULTS: The addition of
      various PGs and isoproterenol relaxed the ciliary muscle that had been
      precontracted with 3 x 10(-6) M carbachol. The relaxation was dose dependent,
      with an EC50 of 2 x 10(-7) M for PGE2. The rank order of potency by which PGs
      induced relaxation (PGE2 = E1 > D2 > F2 alpha > I2) was identical with that
      reported for EP type prostaglandin receptor-mediated responses except for PGD2,
      which was more potent than expected. Agents that increased cellular cAMP, such as
      forskolin and IBMX, also relaxed the precontracted muscle. Nitric oxide donors,
      such as sodium nitroprusside and S-nitroso-N-acetyl-DL-penicillamine (SNAP), also
      caused dose-dependent relaxation. PGs and isoproterenol, but not nitroprusside,
      stimulated adenylate cyclase. The rank order of potency by which PGs stimulate
      adenylate cyclase was similar to that observed for muscle relaxation, suggesting
      that cAMP is the cellular second messenger for the PG-induced muscle relaxation
      and thus that PG receptors of EP2 and DP type are involved. CONCLUSIONS:
      Relaxation of cat ciliary muscle is mediated by two independent mechanisms: a
      cAMP-dependent one, which includes beta-adrenergic, EP2, and DP receptor-mediated
      responses, and a cAMP-independent one, which includes the nitric oxide-induced
      mechanism.

PMID- 7730030
TI  - Soluble forms of the high-affinity fibroblast growth factor receptor in human
      vitreous fluid.
AB  - PURPOSE: Fibroblast growth factor-binding proteins (FGF-BPs) have been identified
      recently in blood and other biologic fluids and have been shown to be identical
      to a truncated form of the high-affinity cell surface FGF receptor. The authors
      examined the hypothesis that FGF-BPs also are present in human vitreous fluid.
      METHODS: Vitreous fluid obtained from 12 patients was incubated overnight with
      heparin-Sepharose, FGF-2 heparin-Sepharose, and wheat germ agglutinin (WGA)
      Sepharose, a lectin known to bind to high-affinity FGF receptors. The
      precipitated proteins were characterized by immunoblotting using two FGF receptor
      antibodies raised to either the extracellular domain of FGFR-1 or the
      intracellular domain of FGFR-1. RESULTS: A 70- to 85-kd FGF-BP was detected in
      the vitreous in each of the 12 eyes examined. A 55-kd FGF-BP was detected in six
      of the samples. Both the 70-to 85-kDa and the 55-kDa proteins were precipitated
      by FGF-2 heparin-Sepharose but not by heparin-Sepharose alone, suggesting that
      the interaction was dependent on the presence of FGF-2. The proteins bound avidly
      to WGA-Sepharose. Western blot analysis revealed that the proteins were
      recognized by an antibody raised to the extracellular domain of the high-affinity
      FGF receptor but not by an antibody raised to the intracellular domain of the FGF
      receptor, indicating they are likely to be truncated portions of the
      extracellular domain of the high-affinity FGF receptor. CONCLUSIONS: Vitreous
      fluid contains 70- to 85-kd and 55-kd FGF-BPs that have biochemical and
      immunologic characteristics similar to the extracellular domain of the high
      affinity FGF receptor. These naturally occurring FGF-BPs may sequester free FGF
      in the vitreous cavity and may modulate the biologic activity of FGF in
      vitreoretinal diseases.

PMID- 7730031
TI  - Death at an early age. Apoptosis in inherited retinal degenerations.

PMID- 7730032
TI  - IP3 generation increases rod outer segment phagocytosis by cultured Royal College
      of Surgeons retinal pigment epithelium.
AB  - PURPOSE: To measure outer segment phagocytosis in cultures of Royal College of
      Surgeons (RCS) rat retinal pigment epithelium (RPE) that have been treated with
      carbachol. Carbachol treatment of RCS RPE results in an increase in the second
      messenger inositol triphosphate, which mimics that observed in normal RPE after
      interaction with rod outer segments (ROS). METHODS: Cultures of RCS RPE were
      phagocytically challenged with isolated rat ROS for 2 hours. Carbachol (1 mM) was
      added to some cultures to stimulate inositol triphosphate synthesis, and
      incubation continued for 30 minutes at 37 degrees C. Inositol triphosphate
      concentration was measured by radioreceptor assay. Bound and ingested outer
      segments were quantified by double immunofluorescent staining. Ingestion of outer
      segment membranes was confirmed by electron microscopy and immunogold staining.
      RESULTS: Carbachol treatment was associated with a rapid and temporary increase
      in inositol triphosphate levels. Royal College of Surgeons rat RPE phagocytically
      challenged with outer segments and treated with carbachol showed significantly
      higher ingestion (34%) compared to untreated RCS RPE (9%) (P < 0.05).
      CONCLUSIONS: Exposure of cultured RCS RPE to carbachol increases the
      intracellular concentration of inositol triphosphate and enhances phagocytosis of
      bound ROS. These results support the hypothesis that the phagocytic defect in RCS
      RPE is related to an abnormality in the generation of inositol triphosphate as a
      second messenger after outer segment recognition and binding.

PMID- 7730033
TI  - Apoptotic photoreceptor degeneration in experimental retinal detachment.
AB  - PURPOSE: To investigate the possibility that cell death in retinal detachment may
      occur by reactivation of apoptotic programmed cell death mechanisms. METHODS:
      Unilateral retinal detachments were created in adult cats using 0.25% sodium
      hyaluronate; detached and control retinas were studied at different intervals.
      Internucleosomal DNA fragmentation (one of the landmarks of apoptosis) was
      investigated in tissue sections with the TUNEL technique, which uses terminal
      transferase to label with biotinylated nucleotides the 3' ends of DNA fragments.
      Sections also were labeled with propidium iodide, which intensely stains pyknotic
      nuclei. In addition, one time point was selected for analysis with electron
      microscopy. RESULTS: TUNEL-positive (T+) and propidium iodide-positive (PI+)
      cells almost never were observed in retinas from control eyes, but they were
      abundant at defined time points after retinal detachment, appearing almost
      exclusively in the photoreceptor layer. Their frequency was particularly high 1
      to 3 days after detachment but declined rapidly over the next several weeks. T+
      cells were still present 28 days after retinal detachment. Electron microscopy
      also revealed evidence of apoptotic cells after retinal detachment. CONCLUSIONS:
      Results are consistent with the hypothesis that photoreceptor degeneration after
      retinal detachment occurs through apoptosis, usually associated with intrinsic,
      programmed cell death mechanisms. The detection of a rapid wave of photoreceptor
      degeneration seems to suggest that early therapeutic interventions might be
      recommended; agents capable of interfering with the apoptotic mechanism could
      have a role in the prevention of cell losses that represent a critical
      complication of retinal detachment.

PMID- 7730034
TI  - Hyperthermia accelerates retinal light damage in rats.
AB  - PURPOSE: To study the time course of visual cell damage resulting from
      hyperthermic light exposure and the possible involvement of rod outer segment
      (ROS) lipids in the process. METHODS: Rats were acclimated in darkness for 2
      hours in a hyperthermic chamber to elevate core body temperature and then exposed
      to intense green light for up to 4 hours during hyperthermia. After light
      exposure, the animals were either sacrificed immediately for biochemical or
      morphologic analysis of retinal light damage or returned to darkness for up to 2
      weeks at ambient temperature before analysis. Rod outer segment lipid profiles
      were characterized, and visual cell loss was determined by rhodopsin and visual
      cell DNA measurements. Morphology was performed at the light and electron
      microscopic level. RESULTS: Retinal damage resulting from hyperthermic light
      exposure was found to be temperature, time, and light intensity dependent. At an
      elevated environmental temperature of 34.5 degrees, 50% visual cell loss was
      found after 1.5 hours of 1100 lux light exposure; the same degree of visual cell
      loss occurred after only 1 hour when rats were maintained at 37 degrees C. At
      ambient temperatures, 4 hours of light exposure had no effect on visual cell
      loss. Irrespective of environmental temperature, when rats were maintained in
      darkness no visual cell loss occurred. Whereas docosahexaenoic acid (22:6) was
      unchanged in the purest fraction of ROS isolated immediately after light
      treatment, a 5 mol% loss of the polyunsaturated fatty acid was found in ROS
      isolated 2 or 24 hours after light exposure. Rod outer segment lipid composition
      was largely unaffected by hyperthermic light exposure, but the density of some
      ROS increased. Morphologically, the ROS appeared to be nearly normal immediately
      after hyperthermic light exposure and structurally more abnormal 2 and 24 hours
      later. The retinal pigment epithelium exhibited damage immediately after
      exposure, which also increased 2 and 24 hours later. CONCLUSIONS: Hyperthermia in
      rats dramatically accelerates retinal light damage compared with light exposure
      under euthermic conditions. Over loss of ROS 22:6 does not occur during
      hyperthermic light exposure, but it is apparent during the 24-hour period after
      light treatment. This suggests that the disappearance of 22:6 from ROS occurs in
      tandem with the process of visual cell death resulting from retinal light damage.

PMID- 7730035
TI  - Long-acting contraceptives. Ethical guidance for policymakers and health care
      providers.
AB  - Realizing the promise of long-acting contraceptives depends on continuing efforts
      to distinguish appropriate from inappropriate policies and practices. The current
      debates concerning Norplant and other long-term methods generally have based
      ethical judgment on too slim a reed. It is insufficient and overly divisive to
      limit the tools of analysis to questions of freedom and coercion. A richer
      perspective is needed. We have sketched out an alternative approach that rests on
      a close, case-by-case analysis attentive to the social dimension and consequences
      of contraceptive decisionmaking, as well as to the individual interests at stake.
      The approach also takes special note of the need for access to long-acting
      contraceptive, the possibility for mistaken nonuse as well as mistaken use, and
      our country's past and present biases and power imbalances. We do not claim that
      this method will make judgments about justifiable or unjustifiable influence easy
      or automatic. However, it should prove adept at underscoring the factors that
      require particular scrutiny. Perhaps more importantly, the approach highlights
      that influences for the use of long-acting contraceptives ought to be judged, not
      merely dismissed.

PMID- 7730036
TI  - Long-acting contraceptives. Rationale, current development, and ethical
      implications.

PMID- 7730037
TI  - Long-term contraceptives in the criminal justice system.

PMID- 7730038
TI  - Coercion and long-term contraceptives.

PMID- 7730039
TI  - Norplant and irresponsible reproduction.

PMID- 7730040
TI  - Reproductive responsibility and long-acting contraceptives.

PMID- 7730041
TI  - Feminism, social policy, and long-acting contraception.

PMID- 7730042
TI  - Contraceptive policy and ethics. Illustrations from American history.

PMID- 7730043
TI  - Challenging medical authority. The refusal of treatment by Christian Scientists.

PMID- 7730044
TI  - The "vampire project".

PMID- 7730045
TI  - A kilobyte of cure.

PMID- 7730046
TI  - The pro-life maternal-fetal medicine physician. A problem of integrity.

PMID- 7730047
TI  - Integrity, abortion, and the pro-life perinatologist.

PMID- 7730048
TI  - Do we need another advisory commission on human experimentation?

PMID- 7730049
TI  - The forgetful mourner.

PMID- 7730050
TI  - Sledding in Oregon.

PMID- 7730051
TI  - The puzzle of profound respect.

PMID- 7730053
TI  - Awe diminished.

PMID- 7730052
TI  - The business of research.

PMID- 7730054
TI  - Human identity and the primitive streak.

PMID- 7730055
TI  - Add professors and stir.

PMID- 7730056
TI  - Doing things with embryos.

PMID- 7730057
TI  - Caring for patients in cross-cultural settings.

PMID- 7730058
TI  - Application of the HSEF to assessing radiation risks in the practice of radiation
      protection.
AB  - The primary risk coefficients upon which exposure limits for radiation protection
      purposes are currently based are derived almost exclusively from cancer-induction
      data obtained from human populations exposed to radiations of low linear energy
      transfer. The question of higher linear energy transfer radiations is handled by
      means of quality factors derived from values for relative biological
      effectiveness obtained from animal data. However, the advent of microdosimetry
      has made it possible to establish hit size effectiveness functions from single
      cell systems, both in vitro and in vivo. This type of function can substitute
      completely for the concept of relative biological effectiveness, Q and equivalent
      dose. A common basis for risk coefficients and the hit size effectiveness
      function lies in the fact that human cancers are monoclonal and thus single cell
      in origin. The present communication utilizes this common base as a means of
      extending the present low-linear energy transfer based risk coefficients to
      include carcinogenic responses from exposure in radiation fields of any one or
      mixed qualities, extending from the smallest to the largest linear energy
      transfers of practical consequence. In doing so, risks from ionizing radiations
      of any linear energy transfer may be predicted more accurately than at present.

PMID- 7730059
TI  - Prevalence of lens changes in Ukrainian children residing around Chernobyl.
AB  - The objective of this study is to determine the prevalence and characteristics of
      lens changes in the eyes of a pediatric population, 5-17 y old, living in the
      permanent control zone around the Chernobyl nuclear reactor and to compare these
      findings with those from an unexposed control population. A total of 1,787
      children are reported on (996 exposed and 791 unexposed). Over three-quarters of
      the subjects examined in this study show a form of minor change, termed focal
      lens defect, in the cortical and/or nuclear portions of the lens of the eye. The
      exposed group shows a small (3.6%), but statistically significant excess (p =
      0.0005) of subclinical posterior subcapsular lens changes similar in form to
      changes identified in atomic bomb survivors. These posterior subcapsular changes
      tend to occur in boys 12-17 y old and in exposed children who report consuming
      locally grown mushrooms on a regular basis.

PMID- 7730060
TI  - Somatic-cell mutations as a possible predictor of cancer risk.
AB  - The somatic-mutation theory of carcinogenesis has received strong scientific
      support from results of recent studies on tumor-suppressor genes. We anticipated
      that people among the high risk for cancer group, either through exposure to
      various ionizing radiations or by virtue of unique genotypes, would also manifest
      increased frequencies of somatic mutation. This report presents the results of
      two somatic-mutation assays--at the erythrocyte glycophorin A (GPA) and
      lymphocyte T-cell receptor (TCR) genes--in various groups at high risk for cancer
      development, including atomic-bomb survivors, patients with various cancers,
      patients administered Thorotrast, and patients with genetic disorders that make
      them cancer prone. Although neither the GPA-mutation nor the TCR-mutation assay
      detects gene mutations directly related to carcinogenesis, increased mutation
      frequencies were detected by both assays in many individuals among the high-risk
      groups and among cancer patients. We have continued to follow up those
      individuals who show values of about three times higher than those of the control
      group. Thus, these assays may prove useful for identifying high-risk cancer
      groups and for estimating the effects of mutagens. Such information would
      constitute a valuable data base for epidemiological studies.

PMID- 7730061
TI  - Accounting for bias in dose estimates in analyses of data from nuclear worker
      mortality studies.
AB  - Although dose estimates used in epidemiologic studies of nuclear workers are far
      superior to exposure measures used in many epidemiologic studies, they are
      subject to several types of bias. These include bias resulting from practices
      used to measure and record very low doses and from underestimation of dose from
      neutrons. They also include bias resulting because available dose estimates do
      not include dose from internally deposited radionuclides, occupational dose
      received after workers have terminated employment at the facility of interest, or
      dose from background or medical exposures. These biases can potentially distort
      dose-response analyses and lead to biased risk estimates and confidence limits.
      This paper uses data on workers at the Hanford site to investigate the possible
      effects of these biases on dose-response analyses of leukemia and of all cancer
      except leukemia. This is accomplished by conducting analyses based on a variety
      of assumptions regarding the nature and magnitude of these biases. Results were
      not modified greatly (as compared to those based on the dose as recorded) for any
      of the 40 sensitivity analyses presented, including some based on fairly extreme
      assumptions. However, analyses that excluded workers with potential for dose from
      internal depositions and from neutrons did increase both the risk estimate and
      upper confidence limits; it may be desirable to emphasize this approach in future
      presentations. It is recommended that similar sensitivity analyses be performed
      with data from other worker studies, addressing the specific dosimetry problems
      that have been identified in those populations.

PMID- 7730062
TI  - A study of uranium lung clearance at a uranium processing plant.
AB  - A study has been made of the retention of uranium in the lungs of persons exposed
      chronically to low levels of uranium aerosols at the Y-12 Plant. A new
      characterization of the workplace aerosols shows an activity median aerodynamic
      diameter of 8 microns to be representative of the uranium oxides handled at the Y
      12 Plant. The usual ICRP respiratory-system model is employed in conjunction with
      bioassay data from worker exposures to deduce a new set of parameters to describe
      lung clearance of these aerosols. This new assessment leads to good agreement
      between in vivo estimates of uranium lung burdens.

PMID- 7730063
TI  - Investigation of alternate droplet material bubble dosimeters.
AB  - Past theoretical research involving superheated liquid droplet (bubble) neutron
      dosimeters has shown the possibility of using alternate droplet materials in
      order to give the dosimeter improved temperature stability. Based on that
      research testing was conducted on HFC-134a, propylene, propane, and
      hexafluoropropylene to determine (1) the compatibility of the novel superheated
      liquid material with the detector gel matrix material; (2) the gamma sensitivity
      of the detector droplets; (3) the response of the dosimeters as a function of
      neutron energy; and (4) the response of the dosimeters as a function of
      temperature. These tests were conducted at the Armed Forces Radiobiology Research
      Institute using a 60Co source, the Naval Surface Warfare Center using a tandem
      neutron accelerator, and the United States Naval Academy using an unmoderated
      252Cf source. The response of the alternate droplet material dosimeters was
      compared to the response of the original Freon 12 droplet material dosimeter. The
      data indicated that the propane and propylene materials were chemically
      incompatible with the gel material and that the hexafluoropropylene dosimeters
      were sensitive to gamma radiation, thus making these types of dosimeters
      unsuitable. However, the HFC-134a superheated liquid droplets were stable in the
      gel material, responded uniformly over varying neutron energies, and had a
      predictable temperature response.

PMID- 7730064
TI  - A rapid method for the simultaneous determination of gross alpha and beta
      activities in water samples using a low background liquid scintillation counter.
AB  - The radiological examination of water requires a rapid screening technique that
      permits the determination of the gross alpha and beta activities of each sample
      in order to decide if further radiological analyses are necessary. In this work,
      the use of a low background liquid scintillation system (Quantulus 1220) is
      proposed to simultaneously determine the gross activities in water samples.
      Liquid scintillation is compared to more conventional techniques used in most
      monitoring laboratories. In order to determine the best counting configuration of
      the system, pulse shape discrimination was optimized for 6 scintillant/vial
      combinations. It was concluded that the best counting configuration was obtained
      with the scintillation cocktail Optiphase Hisafe 3 in Zinsser low diffusion
      vials. The detection limits achieved were 0.012 Bq L-1 and 0.14 Bq L-1 for gross
      alpha and beta activity respectively, after a 1:10 concentration process by
      simple evaporation and for a counting time of only 360 min. The proposed
      technique is rapid, gives spectral information, and is adequate to determine
      gross activities according to the World Health Organization (WHO) guideline
      values.

PMID- 7730065
TI  - Radon concentrations in residential housing in Hiroshima and Nagasaki.
AB  - A measurement of indoor radon (222Rn) concentrations in Hiroshima and Nagasaki
      was carried out to assess the variability of exposure expected among atomic bomb
      survivors. Two hundred dwellings, mostly belonging to members of the fixed cohort
      of atomic bomb survivors under study by the Radiation Effects Research
      Foundations, were selected for this measurement. The geometric mean values of the
      radon concentrations for 100 dwellings in Hiroshima and 99 dwellings in Nagasaki
      measured by Track-Etch Type SF detectors were 56.8 Bq m-3 and 28.5 Bq m-3,
      respectively. No statistically significant difference was observed between lung
      cancer mortalities in the low-dose range in the two cities. However, apparent
      values of the mortality rate for low dose range in Hiroshima are consistently
      greater than those in Nagasaki. The exposure to radon and its progeny and the
      atomic bomb radiation effect might have some cooperative effects on the lung
      cancer incidence.

PMID- 7730066
TI  - New methods of energy efficient radon mitigation.
AB  - Two new radon mitigation techniques are introduced and their evaluation in a
      field study complemented by numerical model predictions is described. Based on
      numerical predictions, installation of a sub gravel membrane at the study site
      resulted in a factor of 2 reduction in indoor radon concentrations. Experimental
      data indicated that installation of "short-circuit" pipes extending between the
      subslab gravel and outdoors caused an additional factor of 2 decrease in the
      radon concentration. Consequently, the combination of these two passive radon
      mitigation features, called the membrane and short-circuit (MASC) technique, was
      associated with a factor of 4 reduction in indoor radon concentration. The energy
      efficient active radon mitigation method, called efficient active subslab
      pressurization (EASP), required only 20% of the fan energy of conventional active
      subslab depressurization and reduced the indoor radon concentration by
      approximately a factor of 15, including the numerically-predicted impact of the
      sub-gravel membrane.

PMID- 7730067
TI  - Lung dose estimates from 222Rn in Arizona groundwater based on liquid
      scintillation measurements.
AB  - Since August 1989, 222Rn groundwater samples from across the state of Arizona
      have been collected and analyzed using liquid scintillation. Of the 253 specimens
      acquired, 65% have 222Rn concentrations above 11 Bq L-1 (300 pCi L-1), while 16%
      have 222Rn activities over 37 Bq L-1 (1,000 pCi L-1). The geometric mean 222Rn
      concentration for all the wells tested is 13 Bq L-1 x divided by 4; the
      arithmetic mean is 37 +/- 122 Bq L-1. Using the geometric mean, it is estimated
      that an additional tracheobronchial lung dose equivalent of 0.19 mSv y-1 x
      divided by 13.9 is delivered to Arizona residents from the well water to home
      pathway.

PMID- 7730068
TI  - Transmission data for shielding diagnostic x-ray facilities.
AB  - Recently published exposure transmission curves for broad diagnostic x-ray beams
      in lead, concrete, gypsum wallboard, steel, plate glass, and wood have been used
      to calculate the transmission in 5 kVp increments over the 25 to 35 kVp range for
      molybdenum-anode tubes and 50 to 150 kVp for tungsten-anode tubes. The data are
      fit to a three parameter model for ease in calculating the x-ray transmission
      with computers or calculators.

PMID- 7730069
TI  - Design of a benchtop alpha particle irradiator.
AB  - The design, construction and calibration of a convenient irradiator is described
      that provides controlled exposure to a uniform external source of well
      characterized alpha particles at a dose-rate of 0.99 cGy min-1. The use of a
      precis- ion photographic shutter allows the accurate delivery of doses as low as
      0.01 mGy (1 mrad) to cultured cells. Special features also include a helium
      environment and reciprocal collimator that permits the use of collimators with
      different transmission factors to achieve differing dose-rates. A simple method
      is described to characterize the energy spectrum of alpha particles by use of
      particle range as measured by track etch.

PMID- 7730070
TI  - The variation of radon exhalation rates from building surfaces of different ages.
AB  - Standardized activated charcoal canisters (according to the U.S. EPA) have been
      used to collect radon exhaled from concrete surfaces covered with thin plaster
      (categorically different from thick plaster) of 32 buildings of different ages
      (0.5-31 y) in Hong Kong. Concrete surfaces covered with thin plaster is the
      commonest wall configuration in Hong Kong. The canisters are analyzed using gamma
      spectroscopy to obtain the radon exhalation rates. The results show that the
      radon exhalation rate decreases with the building age.

PMID- 7730071
TI  - Measurements of air concentrations of thorium during grinding and welding
      operations using thoriated tungsten electrodes.
AB  - An evaluation was performed to determine whether thorium was present in
      concentrations above the derived air concentration during grinding and welding
      operations using thoriated tungsten electrodes. A few of the advantages of using
      thoriated tungsten electrodes in industry include easier are starting, greater
      stability, and reduced weld metal contamination. The electrodes used in this
      evaluation contained 2% thoria (thorium oxide) and were either 2.4 mm or 3.9 mm
      in diameter. Personal breathing zone and area air samples were collected for the
      experienced welders participating in this evaluation during grinding operations.
      The results during the grinding operations for personal and area air samples were
      generally below the derived air concentration (DAC) for 232Th for solubility
      class Y of 0.04 Bq m-3 (1 x 10(-12) microCi mL-1) as per 10 CFR 20. The area
      samples collected during welding operations were below the DAC.

PMID- 7730072
TI  - Shielding design and dose assessment for accelerator based neutron capture
      therapy.
AB  - Preparations are ongoing to test the viability and usefulness of an accelerator
      source of epithermal neutrons for ultimate use in a clinical environment. This
      feasibility study is to be conducted in a shielded room located on the
      Massachusetts Institute of Technology campus and will not involve patient
      irradiations. The accelerator production of neutrons is based on the 7Li(p, n)7Be
      reaction, and a maximum proton beam current of 4 mA at an energy of 2.5 MeV is
      anticipated. The resultant 3.58 x 10(12) neutrons s-1 have a maximum energy of
      800 keV and will be substantially moderated. This paper describes the Monte Carlo
      methods used to estimate the neutron and photon dose rates in a variety of
      locations in the vicinity of the accelerator, as well as the shielding
      configuration required when the device is run at maximum current. Results
      indicate that the highest absorbed dose rate to which any individual will be
      exposed is 3 microSv h-1 (0.3 mrem h-1). The highest possible yearly dose is 0.2
      microSv (2 x 10(-2) mrem) to the general public or 0.9 mSv (90 mrem) to a
      radiation worker in close proximity to the accelerator facility. The shielding
      necessary to achieve these dose levels is also discussed.

PMID- 7730073
TI  - Adequacy of simulated 24-h urine samples.

PMID- 7730074
TI  - Urinary excretion of uranium and dietary intake.

PMID- 7730075
TI  - 137Cs concentration among children in areas contaminated with radioactive fallout
      from the Chernobyl accident: Mogilev and Gomel Oblasts, Belarus.

PMID- 7730076
TI  - Intensive health visiting and the prevention of juvenile crime.
AB  - Studies have shown that early child-bearing, substance use during pregnancy, and
      perinatal complications are linked to poor child-rearing, consequent childhood
      behaviour problems, later delinquency and criminality. David Farrington presents
      evidence that intensive health visiting programmes, with small caseloads, by
      reducing hyperactivity, school failure and child conduct problems, could
      ultimately cut the incidence of juvenile crime.

PMID- 7730077
TI  - Research: a health visitor skill.
AB  - Health visitors tend not to regard research as a priority, or to see it as a
      specialist skill. Beverley Stokoe argues that health visitors are best-placed to
      research their own practice. Here she describes the methodology she used to
      examine the quality of health visitor interactions with clients.

PMID- 7730078
TI  - How parents can help young visually-impaired children to communicate.
AB  - A study of parents' strategies to communicate with their young visually-impaired
      children has implications for all health visitors working with young children,
      write Vanessa Moore and Helen McConachie. The study highlights the important role
      of naturally-occurring communicative exchanges between parent and young child in
      promoting language development.

PMID- 7730080
TI  - Co-ordinating community child health services.
AB  - This briefing provides an overview of the Audit Commission report, 'Seen but not
      heard': a review of community child health and social services. The report was
      published in June 1994 and provides much useful material for health visitors and
      school nurses arguing for the strengthening of their services. However, the HVA
      believes that in some key areas the report is mistaken in its conclusions.

PMID- 7730079
TI  - When to wean: whose advice do mothers find helpful?
AB  - A survey of the weaning practice of first-time mothers shows that the health
      visitor is the most used and useful source of advice, but infant behaviour
      remains the main influence on parents' practice. Caroline Walker suggests that
      official guidelines may be too rigid to reflect the diversity of individual
      infant's needs as experienced by their carers, and that a more flexible approach
      may be needed if professionals' credibility is not to suffer.

PMID- 7730081
TI  - Smoking. Just a reminder....
AB  - Some 500 primary school children took part in a health promotion campaign
      organised by west Devon school health sister Moira Walley to raise awareness of
      the dangers of passive smoking. Part of the campaign was a competition to make a
      'desk-top reminder' about the dangers of smoking, which produced some original
      and striking results.

PMID- 7730082
TI  - Building better health.

PMID- 7730083
TI  - Something fishy in the milk formula.

PMID- 7730084
TI  - Getting help with special costs.

PMID- 7730085
TI  - Landmark ruling raises compensation issue.

PMID- 7730086
TI  - Freedom from bondage to the weed.

PMID- 7730087
TI  - All pain and no gain.

PMID- 7730088
TI  - Ethnic minorities. National survey reveals worrying trends.

PMID- 7730089
TI  - School health. High hopes, harsh realities.

PMID- 7730090
TI  - Opening the door to homeless households.

PMID- 7730091
TI  - Privatisation by stealth?
AB  - 'Government lights the fuse for privatisation' blazed the Health visitor
      journal's front cover when the NHS and Community Care Act was passed in 1990.
      Since then the debate on the future of the NHS has raged. In the first of a
      series in which different authors look at policy issues, Allyson Pollock argues
      that the introduction of charges for dentistry, eye tests and long-term care--is
      undermining the principle of a universal national healthcare service, free at the
      point of use.

PMID- 7730092
TI  - Preventing criminal disease.

PMID- 7730093
TI  - Cost benefit analysis.

PMID- 7730094
TI  - Gearing up for local pay bargaining.

PMID- 7730095
TI  - Backs against the wall.

PMID- 7730096
TI  - Nurse practitioners. Testing the boundaries.

PMID- 7730097
TI  - Hopes and fears as fundholders take control.

PMID- 7730098
TI  - Health visitor identification of postnatal depression.
AB  - Evaluation of a health visitor project in Sevenoaks demonstrated both the value
      of the Edinburgh postnatal depression scale (EPDS) in the identification of
      postnatal depression, and the positive benefit of health visitor intervention in
      its early stages. But, as Angela Painter reports, the project also underlined the
      need for a ten-week home visit and the obstacles presented by large caseloads,
      poor liaison with other services and purchaser reluctance.

PMID- 7730099
TI  - A multi-disciplinary approach to postnatal depression.
AB  - Many health visitors, GPs and midwives feel frustrated in their attempts to help
      women suffering from postnatal depression, due to a lack of consensus concerning
      diagnosis and treatment. Mary McClarey and Beverley Stokoe outline how an
      awareness that these and other women's mental health needs were not being met led
      to the launch of the Oxford city postnatal depression strategy in April.

PMID- 7730100
TI  - Comrades in adversity: the group approach.
AB  - Women suffering postnatal depression frequently report the additional stress of
      feeling they are alone in their distress. Access to a regular support group to
      discuss their problems with peers can be valuable. Fawnia Pitts describes one
      such health visitor-led group, evaluation of which suggests it is both effective
      and cost-efficient in helping women through postnatal depression.

PMID- 7730101
TI  - Using exercise to tackle postnatal depression.
AB  - High incidence of postnatal depression in her own caseload prompted Anna May to
      launch Dundee's first group for women experiencing this problem. She describes
      how she resourced and set up the group, and the women's perceptions of the
      benefits of its exercise and relaxation regime.

PMID- 7730102
TI  - Promoting peer group support with postnatally depressed women.

PMID- 7730103
TI  - Supporting mothers: an inter-disciplinary approach.
AB  - Having worked as a local health visitor for several years in Orpington, Lily
      Foyster identified a great number of clients suffering from postnatal depression
      and also the lack of support facilities available. She describes how a joint
      approach with the local community mental health service can meet women's
      emotional support needs.

PMID- 7730104
TI  - Postnatal depression. Facilitating peer group support.
AB  - Health visitors and lay people have been working together in Maidenhead to
      support women suffering from postnatal illness. Alison Jones, Tricia Watts and
      Sybil Romain describe how the group supplements medical and psychiatric services,
      by tackling the isolation women with postnatal depression can feel, and helping
      them through until the illness ends.

PMID- 7730105
TI  - 'Babies don't come with a set of instructions': running support groups for
      mothers.
AB  - A successful bid to the health promotion department by an inner city Glasgow GP
      enabled two health promotion officers to offer support groups to mothers with
      young children. Jacki Gordon, Robbie Robertson and Margaret Swan describe their
      approach and how mothers benefited from this additional support.

PMID- 7730106
TI  - Nurse practitioners.
AB  - The department of health is keen to explore the potential of the nurse
      practitioner to substitute some areas of health care for the more expensive
      medical practitioner. The RCN has developed a specialist course for nurse
      practitioners. But as yet there is no clear definition of the role or educational
      status of the nurse practitioner. This professional briefing examines the issues,
      and suggests that attempts to define a specific nurse practitioner discipline and
      role limits its potential, and the potential for the development of current
      community nursing practitioners.

PMID- 7730107
TI  - The new PREP requirements.
AB  - The UKCC post-registration education and practice (PREP) regulations come into
      effect this month. HVA education officer Sarah Forester answers some of the
      questions commonly raised by members about the new requirements for renewal of
      registration.

PMID- 7730109
TI  - Housing. More costs and no benefits.

PMID- 7730108
TI  - Accidental childhood poisoning.

PMID- 7730110
TI  - Pay bargaining. Dashing to local cash.

PMID- 7730111
TI  - Expanding definitions.

PMID- 7730112
TI  - More comments on health insurance.

PMID- 7730113
TI  - Transmission of virus in episodes of encephalomyelitis in swine.

PMID- 7730114
TI  - Like father, like son.

PMID- 7730115
TI  - Leptospirosis.

PMID- 7730116
TI  - Lower urinary tract disease in cats: is diet still a cause?

PMID- 7730117
TI  - The right of property owners to control predators and game.

PMID- 7730118
TI  - Laparoscopic diagnosis and conservative treatment of uterine tear in a mare.

PMID- 7730119
TI  - What is your diagnosis? Radiographic diagnosis--osteochondral fragmentation of
      the patella.

PMID- 7730120
TI  - Vaccination guidelines for small ruminants (sheep, goats, llamas, domestic deer,
      and wapiti). Council on Biologic and Therapeutic Agents and the American
      Association of Small Ruminant Practitioners.

PMID- 7730121
TI  - Plasma von Willebrand factor antigen concentration in dogs with hypothyroidism.
AB  - Plasma von Willebrand factor antigen concentration was measured in 10 dogs with
      hypothyroidism, before and after administration of a replacement dose of
      levothyroxine for 67 +/- 12 days. Results were reported as a percentage of normal
      activity, with plasma pooled from clinically normal dogs given a value of 100%.
      Plasma von Willebrand factor antigen concentration was within reference limits in
      dogs with hypothyroidism (126 +/- 41%) and was significantly (P < 0.01) decreased
      (94 +/- 39%) after treatment with levothyroxine. Contrary to findings in some
      other studies, a deficiency of plasma von Willebrand factor did not appear to
      result from hypothyroidism.

PMID- 7730122
TI  - Granulocytic ehrlichiosis and meningitis in a dog.
AB  - A 4-year-old male mixed-breed dog from the Sierra Nevada mountains in California
      was referred because of epistaxis and signs of cervical pain. Dermacentor
      variabilis ticks were found on the dog at the time of physical examination.
      Clinicopathologic abnormalities included nonregenerative anemia,
      thrombocytopenia, and rare intracytoplasmic morulae within circulating
      neutrophils. Abnormalities of the CSF included pleocytosis and intracytoplasmic
      morulae in approximately 9% of neutrophils. Serum antibody titers for Ehrlichia
      canis (40,960) and Rickettsia rickettsii (5,120) were high, and titer for E equi
      (40) was moderate. Treatment included administration of tetracycline,
      chloramphenicol, doxycycline, and prednisone. The dog had several relapses, but
      long-term remission was eventually achieved. Granulocytic ehrlichiosis has
      previously been associated with anemia, thrombocytopenia, and polyarthritis in
      dogs. This case suggests that granulocytic ehrlichiosis may be associated with
      meningitis and that the organisms that cause granulocytic ehrlichiosis may have
      the same vector as do the spotted fever-group rickettsiae.

PMID- 7730123
TI  - Factor XI deficiency in Kerry Blue Terriers.
AB  - A 9-year-old female Kerry Blue Terrier with postoperative hemorrhage and
      prolonged activated partial thromboplastin and activated clotting times was
      determined to have factor XI deficiency. Transfusions of fresh-frozen plasma
      given on 4 consecutive days transiently returned the values for activated
      clotting time and plasma factor XI activity to within reference range limits and
      controlled the hemorrhage. Analysis of data from 10 other factor XI-deficient
      Kerry Blue Terriers with a tendency for mild posttraumatic or postoperative
      bleeding was suggestive of an autosomal mode of inheritance, with a mild tendency
      for posttraumatic or postoperative bleeding in homozygous and heterozygous dogs.
      Factor XI deficiency is the only contact phase protein defect that causes a
      bleeding disorder in animals, which can be explained by the fact that thrombin is
      more efficient than factor XIIa in activating factor XI. Factor XIa plays a key
      role in sustaining coagulation.

PMID- 7730124
TI  - Arterial hypertension associated with topical ocular use of phenylephrine in
      dogs.
AB  - In 3 dogs scheduled for surgical removal of cataracts, systemic and topical
      treatment with antibiotics and topical ocular treatment with prednisolone,
      atropine, flurbiprofen, and phenylephrine were used to achieve maximal mydriasis,
      with minimal risk of pupillary constriction in response to surgery. Each dog
      developed arterial hypertension, with systolic, diastolic, and mean arterial
      pressures ranging from 170 to 205, 90 to 112, and 123 to 148 mm of Hg,
      respectively. Hypertension was treated with acepromazine maleate (0.001 to 0.005
      mg/kg of body weight) i.v., decreasing arterial pressures to reference values.
      Phenylephrine dosages for topical use ranged from 50 to 367 times greater than
      the i.v. dose required to increase arterial pressure by 50% in anesthetized dogs.
      Although adverse sequelae to these episodes of hypertension were not noticed,
      this report documents the uptake of phenylephrine from topical ocular application
      and suggests the need for dose-response measurements for this adjunct to
      mydriatic treatment in dogs.

PMID- 7730125
TI  - Early postoperative ultrasonographic evaluation of incisional sites in dogs: 15
      cases (1990-1992).
AB  - Ultrasonography of the surgical sites of 15 dogs was performed 3 to 8 days after
      they underwent major orthopedic surgical procedures. Eight dogs were suspected of
      having incision-site complications on the basis of localized signs of pain, heat,
      or swelling and clinical signs of pyrexia, lethargy, or anorexia. Seven dogs had
      apparently normal healing of the incision. Ultrasonography was used to assess and
      compare the character of fluid accumulation, to detect fluid accumulation
      associated with evidence of distal enhancement, and to evaluate gas accumulation
      and disruption of muscle fibers. Ultrasonography of the 8 dogs with complications
      of the incision site revealed fluid accumulation (8 dogs), distal enhancement
      associated with fluid accumulations (2), disruption of muscle fibers (1), and gas
      accumulation (1). Ultrasonography of the 7 dogs with apparently normal healing of
      the incisions revealed fluid accumulations (2 dogs), fluid between fascial planes
      (4), disruption of muscle fibers (1), and gas accumulation (1). Aspirates of
      fluid were obtained from 7 dogs with suspected incision-site infection. Analysis
      of results of cytologic evaluation or bacterial culturing confirmed infection in
      6 dogs and indicated that 1 dog had a sterile hematoma. Ultrasonography is a
      sensitive technique for the detection and localization of fluid accumulations;
      however, the detection of fluid accumulations was not limited to dogs with
      incision-site complications. Fluid accumulations can be evaluated by use of
      ultrasound-guided needle aspiration, which has few associated negative side
      effects. During the early postoperative period, results for fluid evaluation of
      samples obtained by use of accurately placed aspiration needles can be used to
      serve as a guide for further treatment.

PMID- 7730126
TI  - Ventricular tachycardia and myocardial dysfunction in a horse.
AB  - Ventricular tachycardia develops less frequently than supraventricular
      dysrhythmias and generally is more indicative of cardiac disease. The horse in
      this report had clinical signs of lethargy and hypophagia and was determined to
      have sustained ventricular tachycardia. Echocardiography was a valuable
      diagnostic tool and revealed an echodense area in the left ventricle that had
      subnormal ventricular performance. A primary heart problem of an inflammatory
      nature was suspected. The horse responded favorably to treatment with lidocaine,
      antimicrobials, and aspirin, as well as stall rest. The horse was used
      successfully as a sire and hunter-jumper after treatment, but subsequently died
      2.2 years later of massive hemoperitoneum. Necropsy revealed an extensive area in
      the left ventricle that appeared thin and fibrotic.

PMID- 7730127
TI  - Multifocal myositis associated with Sarcocystis sp in a horse.
AB  - Multifocal myositis was diagnosed in a 7-year-old Quarter Horse gelding on the
      basis of history and findings on physical examination, serum biochemical
      analysis, electromyography, and microscopic examination of frozen sections of
      muscle biopsy specimens. Histologic examination of the muscle specimen revealed
      multifocal accumulations of histiocytes, lymphocytes, and plasma cells, with
      attendant myofiber degeneration and necrosis. Parasitic cysts with morphologic
      characteristics of Sarcocystis sp were found in regions of myocyte degeneration
      and necrosis, and in regions of normal muscle. Based on a tentative diagnosis of
      Sarcocystis sp-induced myositis, the horse was treated with
      trimethoprim/sulfamethoxazole and pyrimethamine for 28 days, phenylbutazone for 5
      days, and paddock rest for 30 days. At the end of treatment, the horse had gained
      35 kg, its appetite had returned to normal, and muscle mass was returning to
      normal. Sarcocystis fayeri is the only Sarcocystis sp reported in equine muscle
      in the United States and is rarely associated with acute myositis or muscle
      atrophy. The development of clinical signs in this horse could have been the
      result of an underlying immunosuppression or infection with a particularly
      pathogenic strain or large infective dose of S fayeri.

PMID- 7730128
TI  - Epiglottitis in horses: 20 cases (1988-1993).
AB  - Epiglottitis was diagnosed and treated in 20 horses (13 Thoroughbreds and 7
      Standardbreds) over a 5-year period. Eighteen horses were used for racing, and 2
      Standardbreds were broodmares. Primary clinical signs were exercise intolerance,
      respiratory noise, and coughing. The most common endoscopic diagnosis made by
      referring veterinarians was epiglottic entrapment (11 horses). In 19 horses,
      endoscopic evaluation at admission revealed mucosal ulceration and thickening of
      the lingual surface of the epiglottis. Other endoscopic findings included dorsal
      displacement of the soft palate (14 horses), and dorsal deviation of the
      epiglottic axis (11 horses). Only 1 horse had epiglottic entrapment. Treatment
      consisting of stall confinement for 7 to 14 days, topical administration of a
      solution of furacin, dimethyl sulfoxide, glycerin, and prednisolone, and systemic
      administration of nonsteroidal anti-inflammatory drugs and corticosteroids was
      effective in controlling epiglottic edema and inflammation. Antimicrobials were
      administered to 6 horses. Racing performance of the 18 racehorses was evaluated
      by examination of racing records. One horse was still convalescing at the time of
      the study, and 1 horse had been euthanatized 1 week after treatment for
      epiglottitis because of colic. The remaining 16 horses all started at least 1
      race (mean time between initial examination and start of first race, 74 days;
      range, 8 to 265 days). Thirteen horses started at least 4 races following
      treatment for epiglottitis; racing performance after treatment was the same in 8
      and decreased in 5. Long-term sequelae of epiglottitis included epiglottic
      deformity (5 horses), intermittent or persistent dorsal displacement of the soft
      palate (4 horses), and epiglottic entrapment (1 horse).

PMID- 7730129
TI  - Eradication of pseudorabies virus from three large swine herds achieved by
      management intervention and use of a vaccine with a deletion for glycoprotein I.
AB  - Three large farrow-to-finish swine herds in Illinois, quarantined because of
      infection with pseudorabies virus (PRV), were enrolled in an intensified PRV
      eradication program, with the goal being release from quarantine within 3 years.
      The intervention plan primarily relied on vaccination, using a vaccine with a
      deletion of the genes coding for glycoprotein I, in breeding and
      growing/finishing pigs and decreases of movement and mixing of growing/finishing
      pigs. The initial goal was to decrease viral spread in the growing/finishing
      pigs, thereby enabling production of seronegative replacement gilts. Off-site
      rearing of replacement gilts was implemented in 1 recently infected herd in which
      the seroprevalence in the growing/finishing group was high. Results of bimonthly
      serologic monitoring indicated that there was minimal spread of PRV in the
      growing/finishing pigs after 1 year. Increases in the number of sows culled
      combined with an increase in the number of seronegative replacement gilts
      entering the breeding group resulted in a reduction of sow seroprevalence, so
      that phased test and removal of seropositive breeding stock could commence in all
      3 herds at about 18 months after initiation of the program. Persistent use of the
      test-and-removal procedure and repeated testing for release from quarantine were
      required for the most recently infected herd. All herds were released from
      quarantine within 3 years, indicating that a PRV eradication program based on
      vaccination and management changes designed to minimize the spread of PRV can be
      used in conjunction with test-and-removal procedures to effectively eliminate PRV
      from large farrow-to-finish swine herds.

PMID- 7730130
TI  - Delivery of a live calf after in vitro maturation and fertilization of oocytes
      obtained from ovaries removed from a moribund cow.
AB  - An aged Holstein cow of high genetic merit and economic value was determined to
      have a squamous cell carcinoma of the tarsus. Treatment was unsuccessful, as was
      an attempt at superovulation and embryo collection; thus, the owner elected
      euthanasia. On day 17 of the estrous cycle, the ovaries were removed via
      laparotomy and the cow was immediately euthanatized. Oocytes were aspirated from
      ovarian follicles and subjected to in vitro maturation and fertilization
      procedures. Seven morulae that developed in culture were transferred
      nonsurgically to 3 recipient females, resulting in birth of a full-term healthy
      male calf. In vitro maturation and fertilization procedures can be used to obtain
      offspring from valuable, terminally ill cows for which conventional embryo
      collection techniques have proven unsuccessful.

PMID- 7730131
TI  - Use of echocardiography to detect tumors in the heart of a bull with bovine
      leukosis.
AB  - Echocardiography was valuable in identifying tumorous growth in the cardiac
      tissues of a bull with enzootic bovine leukosis. The tumor was discernable as a
      thickening of the interatrial septum and wall of the right atrium, accompanied by
      an immobile pedunculated mass that originated from the interatrial septum and
      extended into the lumen of the right atrium. The mass did not interfere with
      right atrioventricular valve function. The pedunculated mass and thick portion of
      the atrial wall had a similar echogenic appearance; both were hypoechoic, when
      compared with the wall of the right ventricle. A thin anechoic rim surrounding
      the heart was indicative of mild pericardial effusion. Echocardiographically
      detectable abnormalities in combination with results of other clinical
      examinations were the basis for recommending euthanasia of the bull.

PMID- 7730132
TI  - Toxoplasmosis.

PMID- 7730133
TI  - A human protein with antimutator activity.

PMID- 7730134
TI  - Expression of sialylparagloboside in a case of liposarcoma: aberrant
      glycosylation in tumors arising in adipose tissues.
AB  - Gangliosides of liposarcoma, lipoma and lipids from omental tissues were
      analyzed. By immunostaining after thin layer chromatography, gangliosides of
      liposarcoma were identified as GM3, sialylparagloboside and GD3, whereas those of
      lipoma were GM3 and GD3, and those of fat in omental tissues were GM3, GD1a, GD3
      and some unknown ones. Expression of sialylparagloboside is thought to be very
      rare.

PMID- 7730135
TI  - Interleukin-12 augments the generation of autologous tumor-reactive CD8+
      cytotoxic T lymphocytes from tumor-infiltrating lymphocytes.
AB  - Human tumor-infiltrating lymphocytes (TIL) were obtained from breast cancer,
      renal cancer or neuroblastoma to investigate the generation of autologous tumor
      reactive CD8+ cytotoxic T lymphocytes (CTL). When TIL were cultured with
      interleukin (IL)-2 (100 U/ml), the growth of TIL peaked around 8-10 days after
      the initiation of culture. In contrast, the proliferation of TIL cultured with IL
      2 plus IL-12 peaked around 4-5 days after culture and tumor cells rapidly
      disappeared from the culture. To determine the generation of autologous tumor
      reactive CD8+ CTL, TIL-derived CD8+ T cells were separated by FACStar. Both IL-2
      activated and IL-2 plus IL-12-activated TIL-CD8+ T cells showed the same level of
      lymphokine-activated killer activity against a variety of tumor cells. However,
      TIL-CD8+ T cells activated with IL-2 plus IL-12 revealed greatly augmented
      cytotoxicity against autologous tumor cells compared with that induced by IL-2
      alone. The autologous tumor cell-killing activity of TIL-CD8+ CTL was
      significantly inhibited by the addition of F(ab)2 anti-CD3 monoclonal antibody,
      indicating that these CTL recognize autologous tumor antigen through T cell
      receptor. These results imply that IL-12 is a novel cytokine which facilitates
      the generation of autologous tumor-reactive CD8+ CTL from TIL.

PMID- 7730136
TI  - Detection of p53 gene mutations in aspiration biopsy specimens from suspected
      breast cancers by polymerase chain reaction-single strand conformation
      polymorphism analysis.
AB  - Genomic DNA was extracted from aspiration biopsy specimens taken from 15
      suspected cases of breast cancer, including 7 known cases of breast cancer, and
      the p53 gene was studied for evidence of mutation by using a polymerase chain
      reaction-single strand conformation polymorphism (PCR-SSCP) analysis. In 5 of the
      15 cases (33%), p53 gene mutation was identified and these tumors were
      subsequently histologically diagnosed as malignant. Further, DNA flow cytometry
      of the 15 tumors demonstrated that 6 (40%) were aneuploid and malignant, whereas
      9 (60%) were diploid and benign. It was also found that the tumor cells in 5
      aspirated cases that showed p53 gene mutations were all aneuploid, the p53
      protein expression was positive, and the tumors were proved to be histologically
      malignant. It was thus concluded that the detection of p53 gene mutation by PCR
      SSCP analysis of aspirated biopsy specimens from suspected breast cancers is a
      helpful method for achieving a more accurate diagnosis.

PMID- 7730137
TI  - A large-scale, hospital-based case-control study of risk factors of breast cancer
      according to menopausal status.
AB  - We conducted a large-scale, hospital-based case-control study to evaluate
      differences and similarities in the risk factors of female breast cancer
      according to menopausal status. This study is based on a questionnaire survey on
      life style routinely obtained from outpatients who first visited the Aichi Cancer
      Center Hospital between January 1, 1988 and December 31, 1992. Among 36,944
      outpatients, 1,186 women with breast cancer detected by histological examination
      were taken as the case group (607 premenopausal women and 445 postmenopausal
      women) and 23,163 women confirmed to be free of cancer were selected as the
      control group. New findings and reconfirmed factors of breast cancer were as
      follows. 1) The risk of at least one breast cancer history among subjects' first
      degree relatives was relatively high among pre- as well as post-menopausal women.
      2) A protective effect of physical activity against breast cancer was observed
      among both pre- and post-menopausal women. 3) Dietary control decreased the risk
      of premenopausal breast cancer. 4) Current smoking and drinking elevated the risk
      of breast cancer in premenopausal women. 5) Decreasing trends of breast cancer
      risk were associated with intake of bean curd, green-yellow vegetables, potato or
      sweet potato, chicken and ham or sausage in premenopausal women, while in
      postmenopausal women a risk reduction was associated with a more frequent intake
      of boiled, broiled and/or raw fish (sashimi). Further study will be needed to
      clarify the age group- and/or birth cohort-specific risk factors for breast
      cancer among the young generation in Japan.

PMID- 7730138
TI  - Induction of DNA recombination by activated 3-amino-1-methyl-5H-pyrido[4,3
      b]indole.
AB  - To investigate the genotoxic properties of a food-derived carcinogen, 3-amino-1
      methyl-5H-pyrido-[4,3-b]indole (Trp-P-2), we have tested whether Trp-P-2 and its
      metabolically transformed products can induce DNA recombinations. Trp-P-2 is a
      strong mutagen and its activated form, the N-hydroxylated derivative, Trp-P
      2(NHOH), is known to form DNA adducts and cause DNA chain cleavage. Using a
      system in which phage lambda undergoes recombination inside host Escherichia
      coli, we have found that Trp-P-2(NHOH), but not Trp-P-2 itself, can induce
      recombination. A nitroso derivative of Trp-P-2, Trp-P-2(NO), which can be reduced
      intracellularly to form Trp-P-2(NHOH), also induced recombination. Active oxygens
      are implicated in this recombinogenic action, since Trp-P-2(NHOH) is known to
      undergo spontaneous oxidative degradation, generating active oxygen radicals
      which can cause DNA chain cleavages. 4-Hydroxyaminoquinoline N-oxide and phenyl
      hydroxylamine also showed recombinogenic actions in this assay system; hence, it
      is suspected that aromatic amine-type carcinogens have this property in common.

PMID- 7730139
TI  - Modification by analgesics of lesion development in the urinary tract and various
      other organs of rats pretreated with dihydroxy-di-N-propylnitrosamine and uracil.
AB  - Effects of the analgesics phenacetin, acetaminophen and antipyrine on lesion
      development in the urinary tract and other organs in male F344 rats were
      investigated. Animals were concurrently administered with 0.1% dihydroxy-di-N
      propylnitrosamine (DHPN) in drinking water and 3.0% uracil in the diet for 4
      weeks and then, starting 1 week after the cessation of this treatment, received
      basal diet or diet containing phenacetin, acetaminophen or antipyrine for 35
      weeks. The occurrences of renal cell tumors were increased in the groups given
      phenacetin or antipyrine, as compared with the DHPN + uracil alone controls.
      Antipyrine, but not the two other compounds, also enhanced development of
      hyperplastic lesions in the renal pelvis and ureter. In the urinary bladder,
      phenacetin and antipyrine treatments were both associated with increased
      incidence of preneoplastic or neoplastic lesions. Furthermore, phenacetin alone,
      without the initiating agent pretreatments, induced simple hyperplasias of the
      urinary bladder at high incidence. Antipyrine enhanced induction of hyperplastic
      lesions in the ureter and was also found to increase the incidences of
      preneoplastic and neoplastic lesions in the liver. Although decreased incidences
      of tumor development of lung and thyroid were observed for the group given
      phenacetin, this might have been linked to the decreased weight gain. The results
      confirmed that combination treatment with DHPN + uracil is effective for wide
      spectrum initiation of carcinogenesis in the urological tract and demonstrated
      significant modification potential for both phenacetin and antipyrine.

PMID- 7730140
TI  - 1,2-Dibromoethane as an initiating agent for cell transformation.
AB  - The two-stage transformation assay increases the sensitivity of cells to
      chemicals and permits detection of carcinogens acting as initiating agents. 1,2
      Dibromoethane, a representative halogenated aliphatic, has been tested in the two
      stage BALB/c 3T3 cells transformation test at dosage from 16 microM to 128
      microM. This dose range is much lower than those previously found efficient in
      transforming BALB/c 3T3 cells. Apart from the lowest dose, which induced
      borderline effects, all the other assayed dosages appeared to induce heritable
      changes in the target cells. The initiated cells were revealed as fully
      transformed foci both in the combination with a chronic promoting treatment and
      also by allowing cells to perform more rounds of cell replication. The results
      clearly show that 1,2-dibromoethane can act as an initiator of cell
      transformation.

PMID- 7730141
TI  - Association of p53 gene mutations with short survival in pancreatic
      adenocarcinoma.
AB  - Mutations of the p53 gene have been found in a variety of human cancers and are
      implicated in the biologic functions of cancer. To investigate the clinical
      implications of p53 mutations in pancreatic adenocarcinoma, we examined the
      association of mutations of the p53 gene with patients' prognosis. Single-strand
      conformational polymorphism analysis and direct DNA sequencing were used to
      detect p53 gene mutations in 37 pancreatic adenocarcinomas. p53 gene mutations
      were detected in 16 (43%) of the 37 pancreatic adenocarcinomas. Direct sequencing
      did not reveal preferential clustering at any specific codon. There was no
      significant association of the presence of p53 gene mutations with histologic
      types, extent of tumor invasion, the presence of lymph node metastasis, or tumor
      stage. Univariate analysis showed that survival of patients with p53-gene-mutated
      tumors was significantly poorer than that of patients with p53-gene-nonmutated
      tumors (P = 0.02). Cox's multivariate analysis of ten clinicopathologic features
      including p53 gene mutations revealed that presence of p53 gene mutations (P =
      0.026) and curativity of operation (P = 0.014) were independent predictors of
      survival. Furthermore, the survival of patients with p53-gene-mutated tumor was
      significantly poorer than that of patients with p53-gene-nonmutated tumors, both
      in patients who underwent curative operation (P = 0.04) and in patients who
      underwent non-curative operation (P = 0.01). These results suggested that
      mutations of the p53 gene might play an important role in cancer aggressiveness
      and could be a clinically useful predictor of prognosis in patients with
      pancreatic adenocarcinoma.

PMID- 7730142
TI  - Basic fibroblast growth factor as a candidate tumor marker for renal cell
      carcinoma.
AB  - The present investigation was conducted to determine serum levels of basic
      fibroblast growth factor (FGF) by enzyme immunoassay in patients with various
      urogenital tumors. Renal cell carcinoma had a higher tendency (28 of 52, 53.8%)
      toward increased serum levels of basic FGF than any of the other urogenital
      tumors, and increased serum basic FGF was detected more frequently in patients
      with advanced renal cell carcinoma. Analysis of histological pattern indicated
      that renal cell carcinoma with a solid or tubular component is more likely to
      produce basic FGF. However, no significant difference was seen between the
      percentage of clear cell type tumor patients with increased serum basic FGF
      (50.0%) and the percentage of granular cell type tumor patients with increased
      serum basic FGF (66.7%). Five of 8 patients with renal cell carcinoma who
      underwent selective renal venous sampling before nephrectomy showed increased
      serum basic FGF in the renal vein from the affected kidney. After resection of
      the affected kidney to remove the cancer, serum basic FGF disappeared within 2
      weeks. However, residual huge tumor or postoperative disease prolonged the
      increased levels of basic FGF in 2 patients, indicating that basic FGF is
      produced from and secreted by tumor tissue itself. These findings suggest that
      serum basic FGF can be useful in the diagnosis, and in evaluating the prognosis,
      of patients with renal cell carcinoma.

PMID- 7730143
TI  - Mannose-binding protein recognizes glioma cells: in vitro analysis of complement
      activation on glioma cells via the lectin pathway.
AB  - The lectin pathway is a novel pathway for activation of the complement cascade,
      which is initiated by the binding of mannose-binding protein (MBP) to its
      carbohydrate ligands. We investigated whether the complement system was activated
      in vitro by glioma cells through this pathway to the C3 level. MBP was found to
      bind to all six glioma cell lines tested by using flow cytometric analysis.
      Binding of a complex of MBP-associated serine protease and MBP was observed in
      two of the cell lines examined, thereby resulting in C4 consumption. Activation
      of C3 was hemolytically evaluated in these two lines. C3 consumption was also
      observed in one. Based on these results, it is likely that recognition by MBP
      followed by complement activation occurs in certain glioma cell lines.

PMID- 7730144
TI  - Isolation and properties of tumor-derived endothelial cells from rat KMT-17
      fibrosarcoma.
AB  - Rat KMT-17 fibrosarcoma-derived endothelial cells were isolated by Percoll
      gradient centrifugation with an attaching-speed separation technique, and their
      properties in culture were examined. The primary cultured tumor-derived
      endothelial cells (TEC) showed angiotensin-converting enzyme activity, positivity
      for Factor VIII-related antigen staining, and typical capillary-like formation on
      Matrigel. The primary cultured TEC monolayer showed greater permeability than
      normal tissue-derived endothelial cell (aorta, vena cava and epididymal fat
      capillary) monolayers on FITC-dextran diffusion (molecular weight 70,000).
      Leukocyte adhesion to TEC was reduced compared to that to fat-derived capillary
      endothelial cells. These characteristics resembled those of tumor vascular
      endothelium, and were observed both in the primary and first-passage cell
      cultures, but not in the fourth-passage cell cultures. Our findings indicate that
      primary or subcultured TEC are applicable for studies of the physiological
      characteristics of tumor endothelial cells.

PMID- 7730145
TI  - Isolation of a cDNA for a growth factor of vascular endothelial cells from human
      lung cancer cells: its identity with insulin-like growth factor II.
AB  - We have found growth-promoting activity for vascular endothelial cells in the
      conditioned medium of a human lung cancer cell line, T3M-11. Purification and
      characterization of the growth-promoting activity have been carried out using
      ammonium sulfate precipitation and gel-exclusion chromatography. The activity
      migrated as a single peak just after ribonuclease. It did not bind to a heparin
      affinity column. These results suggest that the activity is not a heparin-binding
      growth factor (including fibroblast growth factors) or a vascular endothelial
      growth factor. To identify the molecule exhibiting the growth-promoting activity,
      a cDNA encoding the growth factor was isolated through functional expression
      cloning in COS-1 cells from a cDNA library prepared from T3M-11 cells. The
      nucleotide sequence encoded by the cDNA proved to be identical with that of
      insulin-like growth factor II.

PMID- 7730146
TI  - Preferential production of interleukin-1 beta over interleukin-1 receptor
      antagonist contributes to proliferation and suppression of apoptosis in leukemic
      cells.
AB  - Normal human monocytes were isolated in a nascent state by centrifugal
      elutriation and used for the study of interleukin-1 (IL-1) and interleukin-1
      receptor antagonist (IL-1ra) expression. Neither IL-1 beta nor IL-1ra mRNA was
      present in monocytes just after the isolation, but they were induced
      simultaneously in response to various stimulants. In contrast, only IL-1 beta
      mRNA was expressed in monocytic leukemia cell line JOSK-1, while little or no IL
      1ra mRNA was detected even after stimulation. Dominant expression of IL-1 beta
      over IL-1ra was also observed in fresh leukemia cells including monocytic
      leukemias, i.e., IL-1 beta mRNA was constitutively expressed in 26 out of 36
      cases (72.2%), whereas IL-1ra mRNA was present only in 8 cases (22.2%). The
      signal intensity of IL-1 beta mRNA was stronger than that of IL-1ra even in IL
      1ra-positive cases. Apoptotic cell death of monocytes was significantly inhibited
      by IL-1 beta, and it was enhanced by IL-1ra. In fresh leukemia cells, 3H
      thymidine uptake was generally higher in IL-1-producing cases than in IL-1ra
      producing cases, and was increased by the addition of IL-1 beta in all cases
      tested. Cell proliferation was inhibited by either IL-1ra or anti-IL-1 beta
      antibody in IL-1-producing cases, while it was enhanced by anti-IL-1ra antibody
      in IL-1ra-producing cases. These results suggest that the balance between IL-1
      and IL-1ra is necessary for homeostasis of the mononuclear phagocytosis system.
      The imbalance between these two counter-acting cytokines might contribute to the
      altered growth and accumulation of leukemic cells.

PMID- 7730147
TI  - Inhibition by differentiation-inducing agents of wild-type p53-dependent
      apoptosis in HL-60 cells.
AB  - The product of the p53 tumor-suppressor gene has been shown to function in
      apoptosis and cell cycle regulation. However, there is little information
      regarding the regulation of apoptosis in cell differentiation. We investigated
      the relationship between p53-dependent apoptosis and differentiation induction
      using human promyelocytic leukemia HL-60 cells transfected with pMAMneo
      expression vectors containing dexamethasone-inducible wild-type p53 (wt-p53) cDNA
      inserts. Continuous exposure of the pMAMneo/wt-p53 transfectants to 1 microM
      dexamethasone for more than 24 h caused overexpression of wt-p53 followed by cell
      death with morphological changes typical of apoptosis. Using the wt-p53-inducible
      HL-60 cells, we examined the effects of differentiation inducers on the wt-p53
      dependent apoptosis. All-trans retinoic acid (all-trans RA) at 1 nM or
      granulocyte macrophage colony-stimulating factor (GM-CSF) at 35 pM inhibited the
      wt-p53-induced apoptosis over a 42-h treatment. The apoptosis inhibition by GM
      CSF, but not all-trans RA, was abolished by specific inhibitors of protein kinase
      C. These results suggest that extracellular signals involved in the
      differentiation induction could modulate the wt-p53-dependent apoptosis through
      protein kinase C-dependent and independent pathways.

PMID- 7730148
TI  - Acute induction of adriamycin-resistance in human colon carcinoma HT-29 cells
      exposed to a sublethal dose of adriamycin.
AB  - To study the mechanisms of the acute induction of drug resistance in cancer
      cells, we have established a model system in which adriamycin (ADM) induces
      immediate drug resistance. In this system, human colon carcinoma HT-29 cells were
      pretreated for 1 h with a subtoxic dose of ADM (0.3 micrograms/ml) and incubated
      for 24 h in drug-free medium. Then the cells were treated for 1 h with ADM, and
      the cell survival was determined in terms of colony-forming ability. The survival
      of the pretreated cells was increased up to 100-fold, as compared with that of
      untreated cells. Such increased survival, however, was observed only after high
      doses of ADM (2 to 8 micrograms/ml); more than 99% of the cells were killed.
      These results indicate that only a small fraction of ADM-pretreated cells acquire
      the ADM-resistant phenotype. Similar induced resistance was observed in five of
      seven subclones isolated from HT-29 cells by limiting dilution, suggesting that
      the majority of cells in the parental HT-29 population could acquire the ADM
      resistant phenotype. In the subclone HT-29T9, the ADM pretreatment induced
      concomitant resistance to daunomycin, VP-16, and VM-26 but not to agents other
      than topoisomerase II inhibitors. The ADM-induced drug resistance did not
      accompany MDR1 gene expression and could not be overcome by verapamil, a P
      glycoprotein inhibitor. The present system could be useful to study the acute
      induction mechanism(s) of ADM-resistance, which could be relevant to clinical
      resistance in patients.

PMID- 7730149
TI  - Correlation of gene-specific damage with cisplatin between human adenocarcinoma
      cells and peripheral blood mononuclear cells analyzed by polymerase chain
      reaction-stop assay.
AB  - We investigated gene-specific damage in adenocarcinoma cells, obtained from
      pleural effusions of 9 primary lung cancer patients, induced by incubation with
      cisplatin for 3 h in vitro. The 2.7 kb fragment of the hypoxanthine
      phosphoribosyltransferase (HPRT) gene was amplified by the polymerase chain
      reaction (PCR) to quantify the DNA damage. A 7-fold difference in the extent of
      gene-specific damage among the patients was observed. Mononuclear cells (MNC)
      were obtained from freshly isolated blood from the same patients before they
      received chemotherapy. These cells were also incubated with cisplatin in vitro,
      and PCR amplification of the HPRT gene was carried out. A 4-fold variation of DNA
      damage among the patients was observed. Moreover, there was a linear correlation
      between the extents of the DNA damage in the tumor cells and MNCs (R2 = 0.676, P
      = 0.0016). These results suggest that the PCR-stop assay could be used to detect
      interindividual variations in the extent of gene-specific damage in both tumor
      cells and MNC from the same patients induced by cisplatin treatment. In
      conclusion, MNC could be used to analyze cisplatin-induced gene-specific damage
      in cancer patients whose tumor cells are inaccessible.

PMID- 7730150
TI  - Novel after-loading interstitial photodynamic therapy of canine transmissible
      sarcoma with photofrin II and excimer dye laser.
AB  - Novel after-loading interstitial photodynamic therapy was performed in a canine
      transmissible sarcoma (CTS) model, utilizing photofrin II and an excimer dye
      laser. First, photofrin II was injected intravenously at a dose of 5 mg/kg, then
      48 h later, laser-proof plastic tubing was inserted into the CTS, followed by
      photoradiation of the tumor from the inside. The mean diameter of tumor necrosis
      rapidly increased in parallel with increase in total irradiation energy below 240
      J/cm; the mean diameter of tumor necrosis was 20.7 mm at an energy of 120 J/cm,
      and 24.5 mm at 240 J/cm. Beyond 240 J/cm, the diameter gradually increased to 26
      mm at 960 J/cm. As a side effect, cutaneous tissue showed a deep open ulcer at
      240 J/cm, a shallow open ulcer at 180 J/cm, and a scar healing at 120 J/cm. The
      thermal effect of laser light is considered negligible below 480 J/cm.

PMID- 7730151
TI  - Paeciloquinones A, B, C, D, E and F: new potent inhibitors of protein tyrosine
      kinases produced by Paecilomyces carneus. I. Taxonomy, fermentation, isolation
      and biological activity.
AB  - Paeciloquinones A to F as well as versiconol have been isolated as inhibitors of
      protein tyrosine kinase from the culture broth of the fungus Paecilomyces carneus
      P-177. The novel anthraquinones inhibit epidermal growth factor receptor protein
      tyrosine kinase in the micromolar range. Two compounds, paeciloquinones A and C,
      are potent and selective inhibitors of the v-abl protein tyrosine kinase with an
      IC50 of 0.4 microM. Dependent on the fermentation conditions, partially different
      sets of paeciloquinones may be produced. An HPLC method allows separation of all
      major active components.

PMID- 7730152
TI  - Paeciloquinones A, B, C, D, E and F: new potent inhibitors of protein tyrosine
      kinase produced by Paecilomyces carneus. II. Characterization and structure
      determination.
AB  - Paeciloquinones A to F and versiconol have been isolated as inhibitors of protein
      tyrosine kinases from the culture broth of the fungus Paecilomyces carneus P-177.
      The structures of the new anthraquinones were determined by spectroscopic
      methods, mainly 1H NMR and 13C NMR. The substitution pattern was established by
      investigation of the respective methylated derivatives.

PMID- 7730153
TI  - New glycosidases inhibitors, panosialins D and wD produced by Streptomyces sp. OH
      5186.
AB  - New panosialin analog, panosialins D and wD have been isolated from the culture
      broth of Streptomyces sp. OH-5186. Their structures were elucidated as 5-(13
      methylpentadecyl)-1,3-benzenediol bis(sodium sulfate) and 5-(13-methylpentadecyl)
      1,3-benzenediol 1-(sodium sulfate), respectively. They showed strong inhibitory
      activity against alpha-mannosidase, alpha-glucosidase, and beta-glucosidase.
      Panosialins wA-wD mixture also showed weak mitogenic activity but suppressed the
      mitogen induced activity.

PMID- 7730154
TI  - Terpentecin and ECT4B, new family of topoisomerase II targeting antitumor
      antibiotics produced by Streptomyces: producing organism, fermentation and large
      scale purification.
AB  - Terpentecin and UCT4B are new family of antitumor antibiotics with topoisomerase
      II mediated DNA cleavage activity. Based on the taxonomic studies, the producing
      strain S-464 was identified as Streptomyces sp. This strain is different from
      Kitasatosporia griseola which had been identified as the terpentecin-producing
      strain in 1988. Fermentation studies showed that natural nitrogen sources
      supported higher titer of terpentecin, and the synthetic medium with inorganic
      nitrogen sources supported selective production of UCT4B. An improved isolation
      method was developed for the large scale purification of terpentecin.

PMID- 7730155
TI  - Azicemicins A and B, a new antimicrobial agent produced by Amycolatopsis. I.
      Taxonomy, fermentation, isolation, characterization and biological activities.
AB  - A new structural class of the antibiotic, azicemicins A (1) and B (2) were
      isolated from the culture broth of the strain MJ126-NF4, which was closely
      related to Amycolatopsis sulphurea. They were purified by adsorption on Diaion HP
      20, silica gel column chromatography and preparative TLC. The molecular formulas
      of 1 and 2 were determined to be C23H25O9N and C22H23O9N by HRFAB-MS,
      respectively. Azicemicins A and B have moderate growth inhibiting activity
      against Gram-positive bacteria and mycobacteria.

PMID- 7730156
TI  - Improvement of efficacy of antitumor agents by conagenin.
AB  - The antitumor efficacy of antitumor agents at sublethal doses was investigated in
      combination with conagenin (CNG) against murine leukemias. Mice were inoculated
      with 1 x 10(3) L1210 cells i.v. and given 300 mg/kg of cyclophosphamide (CY) i.p.
      on days 1 and 2 or on days 1, 5 and 9 after the tumor inoculation, and 5 mg/kg of
      CNG daily for 10 days. The administration of CNG was effective in increasing the
      number of cured mice and in prolonging the survival period of mice significantly,
      on both schedules of CY treatment. Moreover, the antitumor effect of CY against
      EL-4 was enhanced by CNG in increasing the number of cured mice, in CY treatment
      on days 1 and 2, and on days 1, 5 and 9. The effect of CNG was examined with
      mitomycin C (MMC) and adriamycin (ADM) at sublethal doses against leukemias. The
      antitumor effects of MMC at 10 mg/kg against L1210, and ADM at 15 mg/kg against
      P388 administered on days 1 and 5 were enhanced by CNG. Although mice treated
      with ADM at 15 mg/kg died earlier than non-treated controls on days 1 and 2
      against L1210, P388 and EL-4, CNG with ADM was effective in prolonging the
      survival period.

PMID- 7730157
TI  - Inhibition of the binding of oxidized low density lipoprotein to the macrophages
      by iturin C-related compounds.
AB  - Binding of modified lipoproteins including oxidized low density lipoprotein
      (oxidized LDL) to cell surface receptors is an initial step of conversion of
      monocyte-derived macrophages into lipid-laden foam cells, a key cellular
      component in the early lesions of atherosclerosis. We have searched for microbial
      metabolites that inhibit oxidized LDL-induced lipid accumulation in macrophages
      and isolated three compounds from a strain of Bacillus sp. as inhibitors of
      oxidized LDL binding. By chemical and spectroscopic analyses, these metabolites
      were shown to be related to the cyclic lipopeptide iturin C. Two of these
      compounds were novel metabolites having long chain beta-amino acid moieties of
      different length. These agents, at concentrations ranging from 5 to 20 microM,
      inhibited cell surface binding of oxidized 125I-LDL, resulting in reduced
      intracellular accumulation and degradation of the lipoprotein as well as in
      reduced cholesteryl ester formation from [14C]oleate in macrophages J774.

PMID- 7730158
TI  - Total structures and antimicrobial activity of bacitracin minor components.
AB  - Total structures of 13 minor components of bacitracin (BC) were proposed, and
      their antimicrobial activities were investigated. The components of BC including
      bacitracins A (BC-A) and F (BC-F) were isolated by preparative HPLC and were
      hydrolyzed under acidic conditions. The resulting amino aids were derivatized
      with 1-fluoro-2,4-dinitrophenyl-5-L-alanineamide and were separated by HPLC to
      determine their absolute configurations. It was found that the N-terminal amino
      acids of BC-A and its related components were epimerized during the hydrolysis to
      yield their enantiomers. The formation of these artifactual amino acids suggests
      that our previously proposed structures of the BC minor components are incorrect;
      therefore, the structures were corrected based on these results. The structures
      of the BC minor components were the same as that of BCs-A and -F except that one
      to three of the L-isoleucines, including the N-terminal one, were replaced by L
      valines. These structures were confirmed by tandem mass spectrometry under fast
      atom bombardment (FAB) conditions and Frit-FAB liquid chromatography/mass
      spectrometry. Based on the UV spectra of the BC components determined by
      photodiode array detection-HPLC analysis, a new systematic nonmenclature was
      proposed for the minor components. The isolated components were also used for the
      determination of their minimal inhibition concentrations and it was found that BC
      A is 2 approximately 8 times more potent than the other minor components against
      strains of Micrococcus luteus and Staphylococcus aureus.

PMID- 7730159
TI  - In vitro study of deoxymethylspergualin on functions of lymphocytes and bone
      marrow cells from healthy volunteers.
AB  - 15-Deoxy-11-O-methylspergualin (MeDSG) is an analogue of 15-deoxyspergualin,
      which has potent immunosuppressive activity. The present study was designed to
      evaluate the in vitro effects of MeDSG on the functions of peripheral blood
      mononuclear cells (PBMC) and bone marrow cells derived from healthy volunteers.
      MeDSG failed to suppress the proliferation of PBMC stimulated with mitogens. In
      the allogeneic mixed lymphocyte reaction, MeDSG strongly suppressed both the
      proliferation of lymphocytes and the generation of alloreactive cytotoxic T
      lymphocytes, but did not affect the cytolytic activity of the established
      cytotoxic T lymphocytes. MeDSG had no effect on the cytolytic activity of natural
      killer cells. Concerning positive hematopoietic regulators, MeDSG had a slight
      enhancing effect on the release of granulocyte-macrophage colony-stimulating
      factor and a slight inhibitory effect on the release of interleukin-6 and
      granulocyte-colony-stimulating factor from PBMC stimulated with mitogens.
      Significantly, MeDSG completely suppressed the colony formation of bone marrow
      cells in the presence of granulocyte colony-stimulating factor.

PMID- 7730160
TI  - 10,11,12,13-Tetrahydro derivatives of tylosin. II. Synthesis, antibacterial
      activity and tissue of 4'-deoxy-10,11,12,13-tetrahydrodesmycosin.
AB  - 4'-Deoxy-10,11,12,13-tetrahydrodesmycosin was prepared in six-step reactions.
      Antibacterial screening shows retained antibacterial spectrum of tylosin with
      some improvement against tylosin-sensitive Staphylococci and Haemophilus
      influenze. However, the pharmacokinetic data demonstrated rapid distribution from
      blood in tissues and prolonged maintenance in all tissues, especially in the
      lungs, in comparison with tylosin.

PMID- 7730161
TI  - Structure activity studies on chemically modified homologues of the antibiotic
      phytotoxic leucinostatin A.
AB  - The synthesis and a conformational study of a number of homologues of the well
      known antibiotic, phytotoxic leucinostatin A are reported. The circular dichroism
      of all the compounds are discussed. Some conclusions on the SAR of these
      compounds are drawn. The influence of the alpha-helical conformation and/or the
      increased lipophile character on their interesting biological activities is
      emphasized.

PMID- 7730162
TI  - Metabolites with nematicidal and antimicrobial activities from the ascomycete
      Lachnum papyraceum (Karst.) Karst. III. Production of novel isocoumarin
      derivatives, isolation, and biological activities.
AB  - During investigations on the influence of CaBr2 on the secondary metabolism of
      Lachnum papyraceum, the production of mycorrhizins and lachnumon type antibiotics
      was strongly inhibited in bromide-containing culture media. Instead, six
      isocoumarin derivatives, 6-hydroymellein (6), 4-chloro-6-hydroxymellein (7), 4
      bromo-6-hydroxymellein (9), 6-methoxymellein (10). 4-chloro-6-methoxymellein
      (11), and 4-chloro-6,7-dihydroxymellein (12) were isolated. Compounds 7, 9, 11,
      and 12 have never been isolated from natural sources. 6-Hydroxymellein has been
      isolated previously from many sources including Gilmaniella humicola and proposed
      to be a precursor of mycorrhizin A (see reference 6). In comparison to the
      mycorrhizins, the isocoumarin derivatives exhibited only weak antimicrobial,
      cytotoxic, phytotoxic, and nematicidal activities.

PMID- 7730163
TI  - New metabolites with nematicidal and antimicrobial activities from the ascomycete
      Lachnum papyraceum (Karst.) Karst. IV. Structural elucidation of novel
      isocoumarin derivatives.
AB  - The structures of four new biologically active halogenated dihydroiso coumarins
      isolated from submerged cultures of the ascomycete Lachnum papyraceum have been
      elucidated by spectroscopic methods. The compounds are structurally related to
      lachnumon and mycorrhizin A, which are also produced by the fungus.

PMID- 7730164
TI  - 5-Hydroxy-9-methylstreptimidone, a new glutarimide from a Streptomyces sp. HIL Y
      9065403.

PMID- 7730165
TI  - Novel cephalosporins having a benzothiopyran group. 1. Synthesis and
      antibacterial activity of cephalosporin derivatives characterized by novel C-3
      substituents of benzothiopyran.

PMID- 7730166
TI  - Novel cephalosporins having a benzothiopyran group. 2. Synthesis and biological
      activity of catecholic benzothiopyran group at the C-3 side chain.

PMID- 7730167
TI  - Sulfinemycin, a new anthelmintic antibiotic: fermentation, isolation and
      structure determination.

PMID- 7730168
TI  - Syntheses and glycosidase inhibiting activities of nagstatin analogs.

PMID- 7730169
TI  - Genetic implications of a bivariate threshold model for litter size components.
AB  - A bivariate threshold model for ovulation rate and embryonic survival was
      developed and the genetic relationships in the observed scale among ovulation
      rate, embryonic survival, and litter size were derived. This model was applied to
      data of nulliparous Lacaune sheep. Heritabilities assumed were .30, .05, and .12
      for ovulation rate, embryonic survival, and litter size, respectively. Three
      values for genetic correlation between ovulation rate and embryonic survival were
      considered: -.78, -.30, and 0. Three criteria to increase litter size were
      studied: a linear index combining ovulation rate and embryonic survival,
      ovulation rate, and litter size. The linear index used gave an increasing weight
      to embryonic survival with higher ovulation rates. A selection scheme was
      simulated to test predications of response for the different criteria. A nucleus
      of 10 sires and 300 dams was simulated. Females were selected according to their
      own performance (mean of three records) and males according to their dam's
      performance. Selection was continued for six discrete generations. Response with
      an index was better than direct selection only in the short term, whereas this
      superiority was not maintained in the last generations of selection. Indirect
      selection on ovulation rate was clearly inferior to both index and direct
      selection. In the situation analyzed here, litter size seems to be close to the
      optimum 'natural index' combining ovulation rate and embryonic survival.

PMID- 7730170
TI  - Productivity through weaning of nine breeds of cattle under varying feed
      availabilities: I. Initial evaluation.
AB  - The effect of varying dry matter availability on the conversion of dry matter
      resources to weight of calf at weaning was evaluated for nine breeds of cattle;
      Angus, Braunvieh, Charolais, Gelbvieh, Hereford, Limousin, Red Poll, Pinzgauer,
      and Simmental were recorded for 5 yr. Within each breed, four cows were assigned
      to each of four feeding levels of dry matter intake: 58, 76, 93, or 111 g of
      DM/wt75. Cows remained on their assigned diet regimen throughout the study.
      Individual cow consumption, daily feed allowance adjusted for refusal, was
      recorded weekly. Production information included birth and weaning weight of the
      progeny, calving rate, and cow weights and condition scores. Cows were exposed to
      bulls of the same breed for 90 d. Reasons for cow replacement included failure to
      conceive in two successive years, injury, Caesarean section, chronic illness, and
      death. Response to dry matter intake (DMI) was curvilinear and differed among
      breeds (P < .10) for calving rate, calf survival, and weight of calf weaned per
      cow exposed. Significant differences occurred among the breeds for the linear
      response to DMI for cow weight and condition score. The response to DMI was
      curvilinear for birth weight (P < .10), but the response did not differ among
      breeds (P > .20). Red Poll exhibited more effective conversion at DMI less than
      4,000 kg/yr, but breeds with greater genetic potential for growth and(or) milk
      production (Gelbvieh, Charolais, Braunvieh, Simmental, Pinzgauer, and Limousin)
      were more efficient at DMI greater than 6,000 kg/yr. Ranking for biological
      production efficiency (weight of calf weaned-cow exposed-1.kg DMI of cow-1)
      through weaning among breeds of cattle varied with dry matter intake.

PMID- 7730171
TI  - Evaluation of line and breed of cytoplasm effects on performance of purebred
      Brangus cattle.
AB  - Substantial differences between reciprocally crossed Bos taurus x Bos indicus
      calves for birth, weaning, and yearling weights have been reported. To determine
      whether cytoplasmic inheritance is responsible for a portion of these
      differences, field records for birth and weaning weight (n = 7,353) and
      postweaning average daily gain (n = 2,746) from registered Brangus calves were
      analyzed. An animal model that included maternal effects was fit for each trait.
      Breed of cytoplasmic origin was fit as a fixed effect and coded as Angus,
      Brahman, or unknown. Cytoplasmic line within each breed of origin was treated as
      a random effect. Variance components for random effects were estimated using
      derivative-free REML procedures. Line of cytoplasm accounted for less than .002%
      of the phenotypic variance in all three traits. Estimates for cytoplasmic breed
      of origin effects were small in magnitude, and contrasts tested (Angus vs Brahman
      and Angus vs Unknown) were not significant (P > .10). Estimates of heritability
      of direct (maternal) effects were .36 (.20), .41 (.27), and .21 (.08) for birth
      weight, weaning weight, and postweaning average daily gain, respectively.
      Estimates of genetic correlations between direct and maternal effects ranged from
      -.27 for postweaning average daily gain to -.58 for birth weight. No evidence for
      breed or line within breed of cytoplasmic origin effects was detected in these
      data.

PMID- 7730172
TI  - The effects of regrouping on behavioral and production parameters in finishing
      swine.
AB  - Three trials involving 396 pigs were conducted to determine the effects of
      regrouping finishing swine (83.8 +/- .69 kg) on weight gain and behavior during
      the subsequent 2-wk period. The methodology between Trials 1, 2, and 3 differed
      primarily in the total number of pigs tested (72, 144, and 180, respectively) and
      the number of pigs per pen (3, 3 or 5, and 5, respectively). In all trials, like
      sexed pigs were moved into a new pen location and allotted to one of three
      treatments: 1) a group of familiar pen mates (Control), 2) a group composed of
      unfamiliar pigs (Mixed), and 3) pigs mixed with strangers for 24 h and then
      reunited with original pen mates for the duration of the trial (Mixed 24 h). In
      the pooled analysis, control pigs gained faster (P < .01) than Mixed pigs (.87
      and .77 kg/d, respectively) over the 2-wk period. Mixed 24-h pigs were
      intermediate in gain (.80 kg/d), indicating that the most severe aggression
      normally observed during the first 24 h accounts for only a portion of the
      setback. Apparently the negative social stress associated with being in the
      presence of unfamiliar pigs persisted beyond the first 24 h and was sufficient to
      limit weight gain over the 2-wk period. Time spent fighting was reduced from 1.72
      min/h during a 6-h period on d 1 to .39 min/h during a 3-h period by d 2 in the
      Mixed group. Fighting was still observed in the Mixed pens 8 d after regrouping
      (.23 min/h), indicative of ongoing social conflicts.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7730173
TI  - Growth patterns and body composition of transgenic mice expressing mutated bovine
      somatotropin genes.
AB  - The objectives of this study were to determine growth rates, feed intakes, feed
      efficiencies, and chemical composition of mice from three transgenic lines in 10
      d periods from weaning to near maturity. Lines M4, M11, and G119K express bovine
      somatotropin (bST) mutations E117L, L121P-E126G, and G119K and display phenotypes
      of large, near normal, and small body size, respectively. M4 mice were 28% larger
      at 28 d and 84% larger at 68 d than non-transgenic control (NTC) mice. M11 mice
      were the same size at 28 d as NTC but were 25% larger at 68 d. G119K mice were
      34% and 25% smaller than NTC at 28 and 68 d, respectively. Growth rates of G119K
      mice and NTC were similar, whereas growth rates of M11 and M4 mice were increased
      (P < .05). Feed intakes of M4 and M11 mice were greater than those of NTC mice (P
      < .05), whereas feed intakes of G119K mice were lower than those of NTC mice (P <
      .05). Feed efficiency (gain/feed) was improved in M4 and M11 mice (P < .05) and
      not altered in G119K mice compared to that of NTC mice (P > .05). Chemical
      composition was also altered by expression of bST analogs in transgenic mice.
      G119K and M4 mice had increased body fat percentages and decreased body protein
      percentages in comparison to M11 and NTC mice (P < .05).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7730174
TI  - Effect of recombinant porcine somatotropin and monoclonal antibody directed to
      ovine somatotrophic hormone on nitrogen retention and immune parameters in pigs.
AB  - Single and combined effects of administration and withdrawal of recombinant
      porcine somatotropin (rpST) and an enhancing murine antiovine growth hormone
      monoclonal antibody (OA15) on nitrogen retention, and serological and
      immunological measurements in pigs were examined in a placebo-controlled
      experiment. Thirty-six barrows were allotted to one of four treatments: control,
      rpST, OA15, and OA15+rpST. The trial phase was four balance periods: a preperiod,
      two periods of treatment, and a postperiod. Weight- and nitrogen gain were higher
      for the rpST group by 13% (P < .01) and 15% (P < .001), for the OA15 group by 8%
      (P < .05) and 9% (P < .05), and for the OA15+rpST group by 25% (P < .001) and 20%
      (P < .001), respectively compared with the control group. During the postperiod,
      weight gain of the OA15- and the OA15+rpST group was 23% (P < .001) and 22% (P <
      .001) lower than that of the control group. Nitrogen gain during the postperiod
      was decreased by 19% (P < .01) for the OA15 group compared with the control
      group. Single or combined administration of rpST or OA15 did not affect (P > .10)
      cellular constituents in the blood of all groups during the periods of
      observation. Animals treated solely with rpST mounted a humoral immune response
      directed to rpST. This anti-rpST antibody response was, however, decreased (P <
      .01) in barrows treated with rpST and OA15 simultaneously. Also, a slight anti
      rpST antibody response was noticed in barrows solely treated with OA15.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7730175
TI  - Effect of age on the differentiation of porcine adipose stromal-vascular cells in
      culture.
AB  - Stromal-vascular (S-V) cells isolated from adipose tissue of newborn pigs (NBPC)
      and mature pigs (MPC) by collagenase digestion were used to evaluate differences
      in preadipocyte culture and development. Cells were seeded at a density of 3 x
      10(4) cells/cm2 on six-well (35-mm) tissue culture plates in 3 mL of DMEM/HAM's
      F12 medium plus 10% fetal calf serum and cultured at 37 degrees C under a
      humidified atmosphere of 95% air:5% CO2 for 24 h. Cells were then washed
      thoroughly in DMEM/HAM's F12 medium without fetal calf serum and maintained in
      serum free (SF) medium or SF medium supplemented with 2.5% newborn pig serum
      (NBPS) or mature pig serum (MPS) for 12 d. After 1 d, more NBPC adhered to the
      culture plates, as indicated by DNA values. After 12 d, protein per culture well
      was not significantly different, but DNA concentration per well remained higher
      (P < .05) in cultures of NBPC than in the MPC cultured in the same medium,
      indicating fewer MPC. Protein:DNA ratios were higher (P < .05) in cultures of MPC
      regardless of the medium, reflecting larger cell size. More cells containing fat
      deposits were seen with NBPC in all conditions in comparison with MPC, and more
      fat was deposited in NBPC in SF than in SF plus NBPS or MPS. The NBPC had higher
      (P < .05) sn-glycerol-3-phosphate dehydrogenase (GPDH; EC 1.1.1.8) per protein
      than MPC regardless of the medium. For both cell types, GPDH activity in either
      serum was less than activity of cells grown in SF.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7730176
TI  - Electromagnetic scanning of beef quarters to predict carcass and primal lean
      content.
AB  - To study the use of electromagnetic scanning in prediction of lean content in
      beef carcasses and cuts, 100 beef cattle (60 steers and 40 heifers), representing
      a broad range in external fat thickness (.1 to 2.9 cm) and live weight (414 to
      742 kg), were selected. Chilled right sides were divided into streamlined
      (foreshank, brisket, and ventral plate removed) forequarters (FQ) and full
      hindquarters (HQ) and scanned. Primal rounds, loins, ribs, and chucks were
      fabricated from the right side, scanned, and physically separated into lean, fat,
      and bone. Prediction equations for dissected lean content and percentage of lean
      included the peak of the electromagnetic scan response curve (obtained from
      scanning the HQ or FQ), length, temperature and weight of the scanned cut, and
      fat thickness at the 12th rib. Using the coefficient of determination, root mean
      square error, and Mallows' Cp statistic, the best model for each dependent
      variable (weight and percentage of lean) that included up to five independent
      variables was selected. Prediction equations for the HQ or FQ of steers accounted
      for 84 to 93% of the variation in lean weight of beef sides and quarters and 71
      to 93% of primals. Sixty-one to 75% of the variation in percentage of lean in
      sides and quarters and 48 to 65% of primals was also explained. Similar results
      were obtained for heifer carcasses. Predicting percentage of lean in any scanned
      cut, rather than weight of lean, accounted for less of the variation. Weight and
      fat thickness contributed significantly when predicting percentage of
      lean.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730177
TI  - Gastric protein breakdown and pancreatic enzyme activities in response to two
      different dietary protein sources in newly weaned pigs.
AB  - Seventy pigs were weaned at 25 d of age and fed diets based on either skim-milk
      powder (SMP) or soybean protein concentrate (SOY). At 0, 3, 6, and 10 d after
      weaning, pigs were anesthetized, their pancreases were removed, and digesta were
      collected from different sections of the digestive tract. The ratio between
      trichloroacetic acid (TCA)-precipitable protein and total (crude) protein (pp:cp)
      in gastric digesta was higher with SOY feed than with SMP feed. In the jejunum,
      no difference was found; hence, the degree of protein breakdown in jejunal chyme
      did not differ between protein sources. Trypsin activities in jejunal chyme and
      in pancreatic tissue increased (P < .01) after weaning. Chymotrypsin activity in
      pancreatic tissue tended to decrease after weaning and did not reach "weaning
      levels" for at least 10 d. Pancreatic trypsin developed more rapidly than
      chymotrypsin after weaning. Chymotrypsin activities in jejunal digesta were
      higher (P < .05) for the pigs fed SMP than for those fed SOY. Protease activities
      in the jejunum at d 6 after weaning were clearly affected (P < .05) by feed
      intake after weaning. The ratio between trypsin and chymotrypsin activity in
      jejunal chyme was higher (P < .05) for SOY-fed pigs than for SMP-fed pigs. It was
      concluded that the stomach plays an important role in the digestion of milk
      protein and that the development of pancreatic proteases after weaning
      (synthesis, secretion, breakdown) depends on feed intake and on dietary protein
      source.

PMID- 7730178
TI  - Determination of apparent ileal amino acid digestibility in pigs: effect of
      dietary amino acid level.
AB  - Studies were carried out to investigate the effect of dietary amino acid level on
      apparent ileal amino acid digestibility. Six barrows, average initial BW 35 kg,
      were fitted with a simple T-cannula at the distal ileum and fed six diets
      according to a 6 x 6 Latin square design. Six cornstarch-based diets containing
      six levels of CP from SBM (4, 8, 12, 16, 20, and 24% CP, respectively) were
      formulated. Chronic oxide was included as a digestibility marker. Each
      experimental period consisted of 8 d. After a 6-d adaptation period, ileal
      digesta were collected for 24 h during d 7 and 9 at 2-h intervals. The pigs were
      fed twice daily, equal amounts, at 0800 and 2000. The dietary allowance was 1,600
      g/d during the first period and increased by 100 g each following period. There
      was a quadratic increase (P < .05) in apparent ileal amino acid digestibility as
      the dietary CP content was increased from 4 to 24%. Initially, the apparent ileal
      amino acid digestibilities increased sharply then gradually reached their
      plateaus, after which there were no further increases and the digestibility
      values became independent of the dietary amino acid levels. The lower end points
      of 95% confidence intervals of the plateau ileal digestibility values were
      defined to be the initial plateau digestibilities. The dietary CP and amino acid
      contents, corresponding to the initial plateau digestibility values, represent
      the dietary threshold levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730179
TI  - The effects of spray-dried blood meal on growth performance of the early-weaned
      pig.
AB  - A total of 1,956 weanling pigs were used in five experiments to evaluate spray
      dried blood meal (SDBM) in starter pig diets. In Exp. 1, 432 weanling pigs
      (initially 6.9 kg BW and 21 d of age) were used to evaluate different protein
      sources in the d 7 to 28 postweaning diet. Pigs were fed a control diet
      containing 5% select menhaden fish meal or diets with 3.88% spray-dried porcine
      plasma, 2.49% SDBM (porcine), 5.74% soy protein concentrate, 5.74% moist extruded
      soy protein concentrate, or L-lysine.HCl and DL-methionine replacing select
      menhaden fish meal on an ideal protein basis. Pigs fed diets containing the spray
      dried blood products had higher (P < .06) mean ADG than pigs fed the other
      protein sources. In Exp. 2, 744 weanling pigs (initially 5.8 kg BW and 21 d of
      age) were used to determine the effects of 0, 1, 2, 3, 4, or 5% SDBM (bovine) in
      the d 7 to 28 postweaning diet. Pigs fed increasing SDBM had greater (quadratic,
      P < .01) ADG and improved gain:feed ratio (G/F). Inflection point analysis
      projected optimum ADG and G/F at 1.9% SDBM. In Exp. 3, 216 weanling pigs
      (initially 10.9 kg BW and 42 d of age) were used to determine the effects of 0,
      .5, 1, 1.5, 2, and 2.5% SDBM (bovine) in the d 21 to 42 postweaning diet. Pigs
      fed increasing SDBM had decreased (linear, P < .05) ADG and G/F. In Exp. 4 and 5,
      144 and 180 weanling pigs (initially 5.3 and 6.2 kg BW and 24 and 21 d of age,
      respectively) were used to evaluate either 2.5% spray-dried porcine, spray-dried
      bovine, or flash-dried bovine blood meal (Exp. 4) or 2.5% spray-dried bovine or
      spray-dried avian blood meal (Exp. 5). Pigs fed diets containing the spray-dried
      blood meals had improved ADG and G/F (P < .01) compared with pigs fed flash-dried
      blood meal. However, no differences (P > .10) were observed among treatments when
      pigs were fed spray-dried blood meals from different species. We conclude that
      spray-dried bovine, porcine, and avian blood meal are effective protein sources
      in starter pig diets (d 7 to 28 postweaning). However, SDBM is not necessary in
      the diets of older pigs (d 21 to 42 postweaning) for maximum growth performance.

PMID- 7730180
TI  - Effects of dietary vitamin E on sow reproductive performance over a five-parity
      period.
AB  - A study involving 360 farrowings over a five-parity period evaluated the effects
      of dietary vitamin E on sow reproductive performance and the subsequent effects
      on serum, colostrum, and milk tocopherol contents. The 2 x 3 split-split-plot
      experiment was conducted at two locations that differed in the type of facility
      (indoor gestation pens/farrowing crates [IP/FC] or outside gestation lots/indoor
      farrowing pens [OL/FP]) and three dietary levels of dl-alpha-tocopheryl acetate
      (22, 44, or 66 IU/kg of diet), with five parities nested within sow in a repeated
      measure design. Sow serum alpha-tocopherol, Se, and glutathione peroxidase (GSH
      Px) activity were measured at 30 and 90 d postcoitum and at 21 d postpartum
      (weaning) during each parity. Colostrum and 7-, 14-, and 21-d milk samples were
      analyzed for alpha- and gamma-tocopherol and Se concentrations. Three pigs per
      litter were bled at weaning and their serum was analyzed for alpha-tocopherol and
      Se concentrations and GSH-Px activity. The results indicated that sow weights and
      daily lactation feed intakes or litter birth and weaning weights were not
      affected by dietary vitamin E levels provided to the sow. There was an increased
      number of pigs born (total, P < .01; live, P < .10) when dietary vitamin E was
      increased. The incidence of mastitis, metritis, and agalactia decreased (P < .05)
      as dietary vitamin E was increased. The incidence of mastitis, metritis, and
      agalactia decreased (P < .05) as dietary vitamin E increased was higher (P < .05)
      with first- and second-litter sows, and was higher (P < .01) at the location that
      had the OL/FP facility. Colostrum and milk alpha-tocopherol increased (P < .01)
      as dietary vitamin E increased. Milk alpha-tocopherol declined linearly (P < .01)
      from 7 to 21 d postpartum in a parallel manner between dietary vitamin E levels.
      At weaning, pig serum alpha-tocopherol increased (P < .01) as sow dietary vitamin
      E level increased. These results support a higher dietary level of vitamin E than
      currently recommended by NRC (1988) for both gestating and lactating sows.

PMID- 7730181
TI  - Efficacy of a copper-lysine complex as a growth promotant for weanling pigs.
AB  - Eight 28- or 35-d experiments involving, 1,301 crossbred pigs weaned at 30 +/- 2
      d of age (7.0 to 7.9 kg initial weight) were conducted to evaluate the efficacy
      of a Cu-lysine complex (CuLys; CuPLEX 80 in Exp. 1 to 5, and CuPLEX 100 in Exp. 6
      to 8) at dietary concentrations of 50, 100, or 200 ppm as a growth promoter for
      weanling pigs. CuPLEX 80 contained 50% Cu in the complexed from (1 mol Cu:2 mol
      lysine) and 50% Cu as CuSO4.5H2O (CuSO4). All the Cu in CuPLEX 100 was in the
      complexed form. In general, the addition of Cu from CuSO4 or either CuLys source
      improved pig performance. Overall, averaged across Cu sources, there were no
      differences between 100 and 200 ppm of Cu in the magnitude of improvement over
      controls for daily gain (14.0 vs 14.3%), daily feed (12.1 vs 10.7%), or feed:gain
      ratio (1.6 vs 3.0%). Averaged across levels of Cu supplementation, the percentage
      improvements from CuLys additions were greater than those for CuSO4 for growth
      rate (16.8 vs 11.5%; P < .03) and feed intake (14.1 vs 8.7%' P < .01), but not
      for efficiency of feed utilization (2.2 vs 2.4%). These trends were similar for
      both sources of CuLys. Liver Cu concentrations of pigs receiving 200 ppm of Cu in
      the totally complexed form (CuPLEX-100) were lower (P < .025) than concentrations
      in those receiving 200 ppm of Cu from CuSO4 (111 vs 221 ppm).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7730182
TI  - Nitrogen utilization and lean growth performance of 20- to 50-kilogram pigs fed
      diets balanced for lysine:energy ratio.
AB  - Two experiments were conducted to determine the lysine:DE ratio that would
      maximize nitrogen retention and lean growth in growing pigs. Diets were
      formulated to contain 2.5, 3.0, 3.5, or 4.0 g of lysine/Mcal of DE at 3.5 and
      3.75 Mcal of DE/kg of diet arranged in a 4 x 2 factorial. Experiment 1 used 48,
      20-kg crossbred barrows in a nitrogen balance study. Feeding diets containing
      3.75 Mcal of DE/kg of diet resulted in higher (P < .01) nitrogen digestibility
      and retention as well as higher energy and DM digestibility. In diets containing
      3.5 Mcal of DE/kg, increasing the lysine:DE ratio had no effect on nitrogen
      retention, but an increase up to 3.0 g of lysine/Mcal of DE was observed at the
      3.75 Mcal of DE level. In Exp. 2, 96 individually housed growing crossbred
      barrows and gilts were used to determine lean and growth performance to the diets
      fed in Exp. 1 in a 4 x 2 x 2 factorial arrangement of treatments. Weight gain was
      unaffected by dietary treatment. A reduction (P < .01) in feed intake and an
      improvement (P < .05) in feed efficiency was observed as the DE level increased.
      Increasing the lysine:DE ratio to 3.0 to 3.5 g of lysine/Mcal of DE increased (P
      < .05) the rate of fat-free lean and empty body protein gain and the weight of
      fat-free lean at 50.9 kg increased (P < .01) with increasing lysine:DE ratio
      regardless of sex or energy level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730183
TI  - Variation among inbred and linecross mice in response to fescue toxicosis.
AB  - Variation in response to fescue toxicosis was examined in inbred and linecross
      mice. In Exp. 1, exposure to a 50% endophyte-infected tall fescue diet (E+)
      reduced ADG of males from six inbred lines, but ADG of males from one line was
      modestly higher on E+. Lines differed (P < .01) for reproductive organ weight,
      but the diet x line interaction was not significant. In Exp. 2, an apparently
      susceptible (C57) and an apparently resistant line (FVB) were mated to produce
      inbred and linecross offspring. The reduction in weight gain caused by the E+
      diet did not differ significantly among the genetic groups. In Exp. 3, C57 and
      C57 backcrosses had smaller reductions in ADG during E+ vs control feeding
      periods than FVB and FVB backcrosses (P < .10). In Exp. 4, the E+ diet reduced
      litter size of mates of C57 males by one pup, whereas litter size of mates of FVB
      males was four pups larger (interaction P = .07). Neither diet, line, nor their
      interaction affected male reproductive organ weights or tissue proportions in
      testis cross-sections. In Exp. 5, the E+ diet did not affect weight gain of C57
      or FVB males, but effects of the E+ diet on litter size of mates were similar to
      those in Exp. 4. Percentage of abnormal sperm was increased in C57 males on the
      E+ diet but decreased in FVB males (Exp. 5). Differences among inbred lines in
      susceptibility to fescue toxicosis may depend on severity of the challenge and
      life cycle stage when the challenge is imposed.

PMID- 7730184
TI  - D2 dopamine receptor response to endophyte-infected tall fescue and an antagonist
      in the rat.
AB  - Effects on rat brain D2 dopamine receptors by endophyte-infected tall fescue seed
      consumption and antagonist injection were characterized. Forty-eight male Wistar
      rats (225 g) in three separate trials were exposed to either 22 or 32 degrees C.
      Diets, to maintain similar concentrations of ergovaline, contained 10% (Trial 1)
      or 15% (Trials 2 and 3) endophyte-infected (E+; 325 average ppb of ergovaline) or
      uninfected (E-; 0 ppb of ergovaline) tall fescue seed. Rats were injected i.p.
      daily with either placebo (PL) or an experimental D2 dopamine antagonist (DA,
      .0375 mg/kg BW). No effects (P > .10) on diet DM intake by E+ ingestion or DA
      injection were detected at 22 degrees C. However, ingestion of E+ reduced (P <
      .01) and injection of DA improved (P < .05) DM intake of rats housed in 32
      degrees C (11.1 vs 15.4 g of DM/d for E+ vs E-, respectively). Whole brain D2
      dopamine receptor density (Bmax) and mRNA were reduced (P < .05) by E+ and
      increased (P < .05) by DA in Trial 1. No treatment effects (P > .10) on cerebral
      cortex alpha 1- and alpha 2-adrenergic or striatal D2 dopamine receptor Bmax were
      measured in Trials 2 and 3. In summary, dietary E+ reduced whole brain D2
      dopamine mRNA and Bmax, whereas injection of DA increased D2 dopamine mRNA. Thus,
      long-term regulation of monoamine receptors seems to be affected by E+ ingestion
      or DA injection.

PMID- 7730185
TI  - Growth hormone and prolactin concentrations in plasma of horses: sex differences
      and the effects of acute exercise and administration of growth hormone-releasing
      hormone.
AB  - Three experiments were conducted to determine 1) the relationship between
      prolactin and growth hormone (GH) secretion in mares and the response to GH
      releasing hormone (GHRH), 2) whether plasma GH and prolactin concentrations
      differed among mares, stallions, and geldings, and 3) whether sexual differences
      existed after administration of GHRH and acute exercise. In Exp. 1, 10-min blood
      samples were collected from 12 mares for 8 h, and GHRH (0, 45, 90, or 180
      micrograms) was administered at 6 h. In Exp. 2, 15-min blood samples were
      collected for 4 h from 10 mares, stallions, and geldings. In Exp. 3, eight horses
      of each sexual status were administered GHRH at 0900; later that day, each horse
      was exercised for 5 min. Blood samples were collected every 10 min around each
      event. In Exp. 1, prolactin concentrations decreased (P < .01) over the 8-h
      period, and there was an average of 2.9 +/- .5 episodes of increased secretion
      during that time; there was no correlation between these episodes and those in GH
      secretion. Prolactin concentrations were not affected (P > .1) by GHRH. In Exp.
      2, average concentrations of GH were 2.4, 8.6, and 8.5 ng/mL for mares,
      stallions, and geldings, respectively; males differed from females (P < .05).
      Stallions and geldings had more (P < .05) peaks in GH concentrations and greater
      (P < .05) amplitude of peaks than mares. In contrast, prolactin concentrations
      were greater (P < .02) in mares and stallions than in geldings. In Exp. 3, GH
      response to GHRH was greater (P < .03) in stallions than in mares or
      geldings.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730186
TI  - Metabolite flux across portal-drained viscera, liver, and hindquarters of
      hyperinsulinemic, euglycemic beef steers.
AB  - Metabolic response to i.v., exogenous insulin was characterized in three younger
      (355 d old, 340 kg BW) and four older (480 d old, 456 kg BW) beef steers. The
      steers had chronic indwelling catheters to allow measurement of blood flow and
      net flux of metabolites across portal-drained viscera (PDV), liver, and
      hindquarters (HQ). Daily N and ME intakes provided at least 1.8 times maintenance
      requirements. Net flux was measured before and after each steer received
      intramesenteric infusions of insulin, which ranged from 5 to 80 mU.h-1.kg BW-1,
      and intrajugular infusion of glucose to maintain euglycemia. Nonlinear fits of
      data provided predictions of maximal glucose entry (Rmax) for glucose infused,
      liver glucose release, HQ glucose uptake, and total glucose entry (TGE, sum of
      glucose infused plus liver release). Differences in BW could account for
      differences (P < .05) in Rmax for TGE between older steers (688 mmol/h) and
      younger steers (493 mmol/h). Plasma insulin needed to elicit half-maximal
      response (ED50) for TGE tended (P < .17) to be greater for older (82 mU/L) than
      for younger steers (49 mU/L). The decrease in liver glucose release in response
      to infusion of insulin was greater (P < .01) for older (-170 mmol/h) than younger
      (-106 mmol/h) steers. The ED50 for liver production of glucose tended (P = .13)
      to be greater for older (45 mU/L) than for younger (5 mU/L) steers. At 80 mU.h
      1.kg BW-1, liver extraction of insulin decreased to approximately 50% of control
      extraction, and arterial insulin concentration was at least 9.4 times control
      concentrations. The PDV release and liver removal of L-lactate and propionate
      were not reduced by insulin infusion, although liver glucose release was 51 and
      76% of control for younger and older steers, respectively. We concluded that
      older steers tended to be less sensitive than younger steers to the effects of
      insulin on glucose metabolism.

PMID- 7730187
TI  - Administration of testosterone during the follicular phase increased the number
      of corpora lutea in gilts.
AB  - The effects of 0 (vehicle), 1, 10, or 100 mg of testosterone, administered on d
      17 and 18 of the estrous cycle (d 0 = 1st d of estrus), on the number of
      preovulatory follicles on d 19 or the number of corpora lutea (CL) and
      blastocysts on d 11 of the subsequent cycle were examined in 82 gilts. The mean
      number of preovulatory follicles increased (P < .01) in a dose-dependent manner.
      Likewise, gilts that received 1, 10, or 100 mg of testosterone had more (P < .05)
      CL than gilts treated with vehicle. The mean number of blastocysts increased (P =
      .06) in gilts receiving 1 mg of testosterone but decreased (P < .05) in gilts
      treated with 10 mg of testosterone compared with gilts receiving vehicle.
      Similarly, recovery rates of blastocysts decreased (P < .05) in gilts treated
      with 10 or 100 mg of testosterone relative to gilts administered 0 or 1 mg of
      testosterone. Plasma concentrations of testosterone and estradiol increased (P <
      .05) 2 h following administration of 1 mg of testosterone on d 17 of the estrous
      cycle. These results indicate that although the 10- and 100-mg dosages of
      testosterone were detrimental to blastocyst survival, the 1-mg dosage increased
      synthesis of estradiol and the number of CL and d-11 blastocysts.

PMID- 7730188
TI  - Effects of blastocoelic expansion and plasminogen activator activity on hatching
      and zona pellucida solubility in bovine embryos in vitro.
AB  - Two experiments were conducted to evaluate factors affecting zona pellucida (ZP)
      solubility in bovine embryos during hatching in vitro. In Exp. 1, the
      relationship between blastocoelic expansion and ZP solubility was determined. Day
      6 embryos (n = 42) with good or excellent quality grades were cultured (Cultured
      embryos), whereas embryos of fair quality (Not-cultured embryos) were immediately
      placed in .2% SDS, and the time required for complete dissolution of the ZP
      (ZPDT) was determined. For Cultured embryos, ZPDT was determined after 192 h of
      in vitro development. Zona pellucida dissolution time was greater (P < .05) in
      Not-cultured embryos than in Cultured embryos and negatively correlated (P < .01)
      with changes in embryonic surface area. In Exp. 2, the effects of suppressing
      plasminogen activator (PA) activity and blastocoelic expansion on hatching and ZP
      solubility were examined. Day-6 embryos (n = 99) were cultured in medium
      containing 0, 10, or 100 IU/mL of human PA inhibitor-2 (PAI-2) and incubated for
      24 to 44 h in medium containing 0, .1, or .5 nM ouabain. Percentages of embryos
      hatching were not different (P > .05) among 0, 10, and 100 IU/mL of PAI-2;
      however, more (P < .05) embryos hatched after exposure to 0 and .1 nM ouabain
      than to .5 nM ouabain. Embryonic PA activity was suppressed (P < .05) by PAI-2,
      whereas exposure to ouabain did not affect (P > .05) PA activity. Mean ZPDT did
      not differ (P > .05) following culture in medium containing PAI-2 or exposure to
      ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730189
TI  - Serum cholesterol concentration of mice selected for litter size and its
      relationship to litter size and testis mass.
AB  - This study assessed the genetic relationship between litter size and serum
      cholesterol concentration and between litter size and testis mass in mice. Mice
      were from a long-term experiment in which selection had occurred for 21
      generations in three replicated lines per criterion of selection (LS = selection
      to increase litter size based on number born; LC = unselected control).
      Thereafter, random mating within lines was practiced. Serum cholesterol
      concentrations were evaluated in female and male mice from two replicates at
      Generation 29 and one replicate at Generation 30. Body weights and blood samples
      were collected from primiparous females 8 d after weaning their pups. Data from
      males were collected as they came out of breeding cages. In addition, the testes
      were excised, stripped clean of connective tissue and the epididymides, and
      weighed. Means for body mass of females and males, serum cholesterol, number
      born, and testis mass were as follows: 35.2 vs 32.5 g (P < .09), 33.9 vs 30.7 g
      (P < .08), 117.5 vs 110.5 mg/dL (P < .08), 14.0 vs 10.3 pups (P < .04), and 126
      vs 122 mg, respectively, for LS and LC. Serum cholesterol was greater in males
      than in females (133.3 vs 95.1 mg/dL; P < .001), but there was no interaction
      between sex and selection criterion. Serum cholesterol concentration was not
      correlated phenotypically to number born or body mass, but it had a small
      negative relationship with testis mass. Therefore, we concluded that selection
      for litter size tended to increase serum cholesterol in addition to the increase
      in number born but did not change testis mass.

PMID- 7730190
TI  - Follicular dynamics, embryo production, and hormonal responses in Brahman heifers
      following sympathetic stimulation.
AB  - The purpose of this experiment was to characterize adrenal and ovarian responses
      to N-methyl-beta-phenethylamine (NMP) or ACTH. Thirty-three heifers with
      functional midcycle corpora lutea were placed on a 4-d superovulation regimen.
      They were injected twice daily with FSH-P and either saline (Control), ACTH (80
      IU), or NMP (1 mg/kg BW). An initial blood collection preceded jugular delivery
      of saline, NMP, or ACTH, i.m. delivery of FSH and PGF2 alpha (d 3), and
      ultrasound (d 1 to 4). A second blood collection was made 6 min after treatment.
      Sampling continued daily until d 13. Embryos (age 6 to 7 d) were collected and
      evaluated. Concentrations of cortisol (posttreatment minus pretreatment) were
      greatest (P < .05) in NMP- and ACTH-treated heifers. Treatment did not affect
      mean numbers of small (< 4 mm), large (> 8 mm), or total follicles on d 2 to 4.
      Heifers receiving NMP had fewer medium follicles (4 to 8 mm) on d 2 and 3, and
      ACTH-treated heifers had fewer medium follicles on d 4 (P < .07). Mean estradiol
      concentrations on d 2 to 4 were unaffected by treatment (P > .32). Following PGF2
      alpha, time to onset of standing estrus was less (P < .05) in Control than in
      ACTH- and NMP-treated heifers (41.4 vs 47.9 and 58.9 h, respectively). A greater
      frequency (P < .05) of reproductive anomalies (no estrus; no ovulation [i.e.,
      progesterone < 1 ng/mL]; luteal failure [i.e., progesterone < 1 ng/mL but embryos
      recovered]) occurred in NMP (5/11) than in Control (0/10) or ACTH (2/10)
      heifers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730191
TI  - Acute progesterone administration regresses persistent dominant follicles and
      improves fertility of cattle in which estrus was synchronized with melengestrol
      acetate.
AB  - Experiments were conducted to determine whether acute progesterone administration
      would regress persistent follicles and improve fertility in heifers and
      postpartum cows fed melengestrol acetate (MGA). In Exp. 1, heifers (n = 13) were
      fed MGA for 11 d (1st d of MGA = d 1). Prostaglandin F2 alpha (PGF2 alpha) was
      administered to heifers on d 2 to regress the corpus luteum (CL). On d 9, heifers
      were randomly assigned to receive an injection of either 200 mg of progesterone
      (PROG) or no hormone (vehicle; VEH). Neither growth of the persistent follicle
      nor plasma estradiol concentrations were altered by administration of VEH, and
      the persistent follicle ovulated after cessation of MGA feeding. Administration
      of PROG regressed the persistent follicle, reduced (P < .05) systemic estradiol
      concentrations, and resulted in ovulation of a newly recruited follicle. In Exp.
      2, heifers were fed MGA for 14 d and were administered either PROG (n = 30) or
      VEH (n = 31) on d 12. When the CL was absent on d 12, synchronization conception
      rate (SCR) and pregnancy rate (PR) were greater (P < .05) for heifers
      administered PROG than for those administered VEH. Neither SCR nor PR were
      different among treatments when the CL was present on d 12. In Exp. 3, cows (n =
      49) were fed MGA for 14 d and were administered either PROG or VEH on d 12. In
      cows lacking a CL (n = 32), administration of PROG increased (P < .05) SCR, but
      not PR. We conclude that acute PROG administration induces turnover of persistent
      follicles and may increase fertility when estrus is synchronized with MGA.

PMID- 7730192
TI  - Isolation and characteristics of the protozoal and bacterial fractions from
      bovine ruminal contents.
AB  - Four cows were fed once a day either a Cocksfoot hay diet (H) or a diet
      consisting of 65% hay and 35% pelleted ground barley (HB). 15(NH4)2SO4 was
      continuously infused into the rumen as a microbial marker and ruminal digesta
      samples were collected during the 24-h postprandial period for the isolation of
      liquid-associated protozoa and bacteria (LAP, LAB) and particle-associated
      bacteria (PAB). There were marked differences between ruminal pH diurnal
      variations with diets H and HB. Irrespective of the diet and sampling time, the
      chemical composition (OM, N, DAPA, 15N) of the protozoa was clearly different
      from that of the bacteria (P < .001). The LAP contained more OM but less N and
      15N than the bacterial fractions. The DAPA used to validate the isolation
      technique for the mixed ciliate population was not detected in protozoal
      fractions. The OM content of LAB was lower than that of PAB, whereas the N, DAPA,
      and 15N contents were higher. The observed effects of diet (P < .01) on LAP mean
      N contents were due to the different N contents of the LAP samples isolated 23 h
      after feeding and were correlated with the variation in the number of
      Endodiniomorphid protozoa (r = .72; P < .05). The N content of LAB was not
      affected (P > .05) by diet but that of the PAB was increased on diet HB (P <
      .05). The diet did not affect the 15N content of any of the three microbial
      populations. However, the 15N content of the bacteria decreased shortly after
      feeding (P < .001).

PMID- 7730193
TI  - Ruminal characteristics, microbial populations, and digestive capabilities of
      newly weaned, stressed calves.
AB  - Eight ruminally fistulated steers, 7 to 8 mo old, were used in a completely
      randomized, 2 x 2 factorial experiment to determine the effects of energy density
      and protein source in receiving diets on in situ DM, NDF, and N disappearance,
      concentrations of ruminal bacteria, protozoa, ammonia, and pH. Two energy
      densities (1.80 and 1.48 Mcal/kg of NEm) and two protein sources (spray-dried
      blood meal [SDBM] and soybean meal [SBM]) were compared. Fistulated steers were
      weaned, transported by truck, and held in a sale barn before their arrival at the
      feedlot. On d 0 (day of arrival at the feedlot), DMI was 62% of DMI on d 7 after
      arrival. Overall, feeding a high-energy diet resulted in lower (P < .01) in situ
      DM disappearance (DMD) of orchardgrass than feeding a low-energy diet at both 24
      and 48 h. In situ 24-h DMD averaged 46.6% on d-3 and 41.6% on d 0, whereas 48-h
      in situ DMD on d -3 and 0 averaged 58.2 and 58.6%, respectively, indicating the
      ruminal microbial population was not inhibited in its ability to digest available
      substrate. Additionally, there were no differences (P > .10) in 48-h in situ NDF
      disappearance between d -3 and 0 (58.8 vs 57.8%), respectively. No differences (P
      > .10) occurred in the concentration of total bacteria, or cellulolytic bacteria,
      due to feed and water deprivation. Concentration of total protozoa was lower (P <
      .05) on d 0 than at any other time. Entodinium averaged 72.5% of genera before
      weaning, and more than 90% of genera found on all treatments by d 21. Diplodinium
      and Epidinium percentages tended to decline after weaning. Isotricha
      concentrations were low and Dasytricha were eliminated after d 7. In conclusion,
      the concentration of ruminal bacteria and the ability to digest available
      substrate were not decreased immediately after weaning, trucking, and 24 h of
      feed and water deprivation.

PMID- 7730194
TI  - Kinetics of fiber digestion from in vitro gas production.
AB  - In vitro gas production, measured by computer-interfaced pressure sensors, was
      used to follow the digestion of a crystalline processed cellulose, a bacterial
      cellulose, and mixtures of these substrates by mixed ruminal bacteria. A first
      order, substrate limited model (simple exponential with lag) and two bacterial
      growth models (logistic, Gompertz) were tested to fit these data. No single pool
      model gave an optimal fit to all substrates, but dual pool versions of both the
      logistic and Gompertz models fitted the data extremely well. Derivations of these
      models in the context of gas production are presented. The dual pool version of
      the exponential model commonly used to analyze fiber digestion was not able to
      reproduce the slope variations seen with mixed substrates. A modified dual pool
      logistic equation, with a single lag value, was selected to model the in vitro
      digestion of these substrates. The model was able to predict adequately both the
      input composition and the kinetic parameters for a defined mixture and gave a
      good fit (r2 > .995) to data from all the single and mixed substrates tested.
      This model may be useful for interpreting gas accumulation from natural
      feedstuffs.

PMID- 7730195
TI  - Ruminal microbiology, biotechnology, and ruminant nutrition: progress and
      problems.
AB  - Present methods for manipulating ruminal fermentation that involve microbial
      biotechnology include dietary ionophores, antibiotics, and microbial feed
      additives. Developments in recombinant DNA technology mean that future methods
      will have a much wider scope. It has been suggested that genetically engineered
      ruminal microorganisms will be used in future to improve ruminal fermentation.
      Several technical objectives must be achieved before that will be possible.
      First, methods for inserting foreign or modified genes into ruminal
      microorganisms and ensuring their efficient expression must be developed. Broad
      host range plasmids and transposons have been used successfully to introduce new
      DNA into ruminal bacteria, as have shuttle vectors constructed as chimeras of
      plasmids from ruminal species and Escherichia coli. Although so far only
      antibiotic resistance markers have been transferred, the prospects for
      introducing other genes into selected ruminal bacteria are excellent. Second, the
      expression of the gene product(s) should be known to be nutritionally useful in
      vivo. A few examples of this type of benefit have been demonstrated, and many
      more proposed, including polysaccharidases for improving fiber digestion, methods
      for improving the amino acid composition of ruminal bacteria, and breakdown of
      plant toxins. Third, the difficulty that has been examined least, yet may prove
      most difficult to overcome, is that mechanisms have to be found for introducing
      and maintaining the new strain in the mixed ruminal population. Factors governing
      the survival of new strains in vivo are ill-understood, and attempts to select in
      favor of added new organisms have so far been unsuccessful. Because of the last
      obstacle, it may be advantageous, at least in the short term, to use nonruminal
      organisms, such as Saccharomyces cerevisiae, rather than indigenous ruminal
      species as a vehicle for implementing the benefits of recombinant DNA technology
      to ruminal fermentation. Yeast is already in widespread use as a feed additive,
      so no enrichment is necessary; and its genetics are already well known.
      Alternatively, adding particular enzymes to the diet may achieve some of the
      objectives described above, with the advantage that the manipulation could be
      achieved without the release of a recombinant microorganism.

PMID- 7730196
TI  - Microbial attachment and feed digestion in the rumen.
AB  - Direct microscopic examination of the rumen and its contents shows microbial
      populations largely attached to feed particles in the digesta. Most feeds contain
      a surface layer that is resistant to attachment and therefore to digestion.
      Infiltration of these recalcitrant epidermal layers through damage sites or
      through focused enzymatic attack is essential for initiation of the digestive
      process. Proliferation of primary colonizing cells produces glycocalyx-enclosed
      microcolonies. Secondary colonizers from the ruminal fluid associate with
      microcolonies, resulting in the formation of multispecies microbial biofilms.
      These metabolically related organisms associate with their preferred substrates
      and produce the myriad of enzymes necessary for the digestion of chemically and
      structurally complex plant tissues. Upon accessing the internal, enzyme
      susceptible tissues, microbial "digestive consortia" attach to a variety of
      nutrients, including protein, cellulose, and starch and digest insoluble feed
      materials from the inside out. Substances that prevent microbial attachment or
      promote detachment (e.g., condensed tannins, methylcellulose) can completely
      inhibit cellulose digestion. As the microbial consortium matures and adapts to a
      particular type of feed, it becomes inherently stable and its participant
      microorganisms are notoriously difficult to manipulate due to the impenetrable
      nature of biofilms. Properties of feed that place constraints on microbial
      attachment and biofilm formation can have a profound effect on both the rate and
      extent of feed digestion in the rumen. Developments in feed processing (i.e.,
      chemical and physical), plant breeding, and genetic engineering (both of ruminal
      microorganisms and plants) that overcome these constraints through the promotion
      of microbial attachment and biofilm formation could substantially benefit
      ruminant production.

PMID- 7730197
TI  - Nutrient transport by ruminal bacteria: a review.
AB  - Fermentation pathways have been elucidated for predominant ruminal bacteria, but
      information is limited concerning the specific transport mechanisms used by these
      microorganisms for C, energy, and N sources. In addition, it is possible that
      changes in ruminal environmental conditions could affect transport activity. Five
      carrier-mediated soluble nutrient transport mechanisms have been identified in
      bacteria: 1) facilitated diffusion, 2) shock sensitive systems, 3) proton
      symport, 4) Na+ symport, and the 5) phosphoenolpyruvate phosphotransferase system
      (PEP-PTS). Several regulatory mechanisms are also involved at the cell membrane
      to coordinate utilization of different sugars. Recent research has shown that
      predominant ruminal bacteria are capable of transporting soluble nutrients by
      several of the mechanisms outlined above. Megasphaera elsdenii, Selenomonas
      ruminantium, and Streptococcus bovis transport glucose by the PEP-PTS, and S.
      ruminantium and S. bovis also possess PEP-PTS activity for disaccharides. Glucose
      PTS activity in S. bovis was highest at a growth pH of 5.0, low glucose
      concentrations, and a dilution rate of .10 h-1. The cellulolytic ruminal
      bacterium Fibrobacter succinogenes uses a Na+ symport mechanism for glucose
      transport that is sensitive to low extracellular pH and ionophores. Sodium also
      stimulated cellobiose transport by F. succinogenes, and there is evidence for a
      proton symport in the transport of both arabinose and xylose by S. ruminantium. A
      chemical gradient of Na+ seems to play an important role in AA transport in
      several ruminal bacteria. Studying nutrient transport mechanisms in ruminal
      bacteria will lead to a better understanding of the ruminal fermentation.

PMID- 7730198
TI  - Rapid communication: PCR-based Sau96I polymorphism in the bovine Lipoprotein
      lipase gene.

PMID- 7730199
TI  - Activity of p-aminobenzoic acid compared with other organic acids against
      selected bacteria.
AB  - The antibacterial activity of p-aminobenzoic acid against Listeria monocytogenes,
      Salmonella enteritidis and Escherichia coli was compared with the activity of
      commonly used acidulants: formic, propionic, acetic, lactic and citric acids.
      Viable count evaluations and MIC determinations indicated that p-aminobenzoic
      acid caused greater inhibitory effects than the other organic acids. The activity
      of p-aminobenzoic acid on the growth of the test organisms at selected pH values
      indicated that p-aminobenzoic acid was more active at low pH than at high pH.
      Uptake studies showed that the uptake of p-aminobenzoic acid by E. coli was
      markedly decreased as the pH values increased. Electron micrographs of E. coli
      cells grown in the presence of p-aminobenzoic acid indicate that p-aminobenzoic
      acid caused marked damage to the cell envelope. It is suggested that p
      aminobenzoic acid has at least two mechanisms of action: one mechanism in common
      with other organic acids and the other mechanism by interfering with the
      synthesis of the peptidoglycan layer by an action on the dihydrofolate reductase
      enzyme.

PMID- 7730200
TI  - Degradation of triglycerides by a pseudomonad isolated from milk: the roles of
      lipase and esterase studied using recombinant strains over-producing, or
      specifically deficient in these enzymes.
AB  - The roles of lipase and esterase in causing hydrolytic spoilage of milk by a
      highly lipolytic psychrotrophic strain of Pseudomonas fluorescens, LS107d2, has
      been studied. Strains of LS107d2 have been constructed that over-produce, or are
      specifically deficient in, a lipase (encoded by lipA) and an esterase (encoded by
      estA). Southern blot analysis reveals that LS107d2 contains only one esterase and
      one lipase (encoded by estA and lipA) and this was confirmed by the phenotypes of
      mutants on triolein and tributyrin-containing agar. Analysis of broth cultures
      showed that the lipase is secreted into the culture medium; in contrast, the
      esterase is not secreted. Free fatty acid (FFA) levels in whole milk cultures of
      wild-type, over-producing and the mutant strains of LS107d2 have been examined.
      From these studies it is concluded that esterase is not involved in the
      accumulation of FFA by hydrolysing short chain fatty acid esters; that the highly
      lipolytic phenotype of LS107d2 is due solely to a single secreted lipase; and
      that the main FFA accumulated in milk cultures of LS107d2 are C4, C16, C18 and
      C18: 1. Evidence is also presented demonstrating that FFA degradation, as well as
      production, determines the level of FFA in milk contaminated with lipolytic
      organisms.

PMID- 7730201
TI  - Partial purification and characterization of bacteriocin from Yersinia
      kristensenii.
AB  - A raw milk bacterial isolate, identified as Yersinia kristensenii was found to
      produce a bacteriocin which was inhibitory to Yersinia enterocolitica but not to
      other selected species of Yersinia or Gram-negative bacteria. Maximum production
      of bacteriocin was obtained when the organism was grown in shake culture at 28
      degrees C. Mitomycin C at a concentration of 0.5 micrograms ml-1 induced
      bacteriocin production. The bacteriocin was partially purified and characterized
      by ammonium sulphate fractionation and gel filtration. The bacteriocin was
      completely inactivated when treated with proteolytic enzymes (trypsin and
      chymotrypsin). Bacteriocin activity was heat-resistant and it retained some of
      its activity after 5 min at boiling temperature. A total of 15 bacteriocin
      sensitive-suspected food isolates were further identified biochemically as
      Yersinia enterocolitica and a non-sensitive isolate was identified as Yersinia
      intermedia.

PMID- 7730202
TI  - Numerical characterization study of Micrococcaceae associated with lamb spoilage.
AB  - A computer-assisted characterization of 296 Micrococcaceae isolates obtained from
      aerobically chill-stored lamb carcasses was carried out using a probability
      matrix and Bayesian identification theorems, complemented with cluster analysis.
      Preliminary identification was done with an original probability matrix
      comprising 37 previously described taxa and 32 tests. Although its statistical
      quality was adequate, the percentage of identification of field strains to
      species level was only 70% (96.6% identified with genera). To achieve an improved
      characterization, cluster analysis was subsequently performed on this group and
      an additional 26% could be associated with defined species, with five more taxa
      defined. The combined use of both approaches was judged positive as new
      identifications and better discrimination could be achieved. The majority of our
      isolates belonged to the Staphylococcus species group. Many species and groups of
      staphylococci increased as the spoilage progressed.

PMID- 7730203
TI  - Antimicrobial activity of the major components of the essential oil of Melaleuca
      alternifolia.
AB  - Tea tree oil, or the essential oil of Melaleuca alternifolia, is becoming
      increasingly popular as a naturally occurring antimicrobial agent. The
      antimicrobial activity of eight components of tea tree oil was evaluated using
      disc diffusion and broth microdilution methods. Attempts were also made to
      overcome methodological problems encountered with testing compounds which have
      limited solubility in aqueous media. After assessing media with and without
      solubilizing agents, the disc diffusion method was used to determine the
      susceptibility of a range of micro-organisms to 1,8-cineole, 1-terpinen-4-ol, rho
      cymene, linalool, alpha-terpinene, gamma-terpinene, alpha-terpineol and
      terpinolene. While the disc diffusion method lacked reproducibility, it was
      considered useful as a procedure for screening for antimicrobial activity.
      Terpinen-4-ol was active against all the test organisms while rho-cymene
      demonstrated no antimicrobial activity. Linalool and alpha-terpineol were active
      against all organisms with the exception of Pseudomonas aeruginosa. Minimum
      inhibitory and minimum cidal concentrations of each component against Candida
      albicans, Escherichia coli and Staphylococcus aureus were determined using a
      broth microdilution method. Modifications to this method overcame solubility and
      turbidity problems associated with the oil components and allowed the
      antimicrobial activity of each of the components to be quantified reproducibly.
      There was reasonable agreement between minimum inhibitory concentrations and
      zones of inhibition. These results may have significant implications for the
      future development of tea tree oil as an antimicrobial agent.

PMID- 7730204
TI  - Selective action of inhibitors used in different culture media on the competitive
      microflora of Salmonella.
AB  - The action of 12 inhibitors employed in the culture media used to detect the
      presence of Salmonella in food on 24 bacterial strains including contaminating
      Gram-positive bacteria common in water and food, Gram-negative bacteria,
      especially Enterobacteriaceae and Pseudomonadaceae, which are components of the
      competitive microflora, and six Salmonella serotypes was tested. Two liquid
      culture media (AR 5 and AE 1) were used. Series of tubes containing increasing
      concentrations of each inhibitor were inoculated with the test strains and
      incubated at 37 degrees C until growth was verified spectrophotometrically (24-48
      h). The results showed that the inhibitors were effective against the Gram
      positive contaminating microflora. They did not preferentially inhibit the
      competitive microflora of Salmonella, chiefly Enterobacteriaceae, and were
      ineffective against the Pseudomonas strains, which can tolerate concentrations
      higher than those customarily employed in culture media.

PMID- 7730205
TI  - Indicator organism sources and coastal water quality: a catchment study on the
      island of Jersey.
AB  - Compliance monitoring of bathing waters at La Greve de Lecq on the North coast of
      Jersey revealed a significant deterioration in water quality between 1992 and
      1993, as indexed by presumptive coliform, presumptive Escherichia coli and
      streptococci concentrations. During the 1993 bathing season the beach failed to
      attain the compliance with the EC Guideline criteria for presumptive E. coli and
      streptococci. A bacteriological survey of the stream catchment draining to the
      beach revealed that: (i) concentrations of faecal indicator organisms were
      enhanced at high discharge after rainfall; and (ii) a captive water fowl
      population, which expanded between 1990 and 1993, was a potential source of
      faecal pollution. Strategies for catchment management are discussed.

PMID- 7730206
TI  - Antibacterial effect of protamine assayed by impedimetry.
AB  - Impedimetric measurements were used to assay the antibacterial effect of
      protamine. A good linear correlation between the impedance detection time and the
      initial cell counts was obtained (r = 0.99, n = 2). As basic peptides may cause
      clumping of cells, this correlation curve was used when estimating the cell
      number after protamine treatment, rather than colony counts. Protamine from
      salmon killed growing Gram-positive bacteria and significantly inhibited growth
      of Gram-negative bacteria in Tryptone Soy Broth (TSB) at 25 degrees C. In general
      Gram-positive bacteria were more sensitive to protamine than Gram-negative
      bacteria; the minimum inhibitory concentrations (MIC) determined for Gram
      positive strains varied from 20 to 1000 micrograms ml-1 and for Gram-negative
      strains from 500 micrograms ml-1 to more than 4000 micrograms ml-1. The effect of
      protamine on non-growing Listeria monocytogenes Scott A suspended in buffer was
      not lethal as was the effect on growing cells; however, protamine (50-500
      micrograms ml-1) killed the Gram-negative fish spoilage bacteria Shewanella
      putrefaciens when the live cells were suspended in buffer.

PMID- 7730207
TI  - Development of a detection system for histidine decarboxylating lactic acid
      bacteria based on DNA probes, PCR and activity test.
AB  - On the basis of the comparison of the nucleotide sequences of the histidine
      decarboxylase genes (hdcA) of Lactobacillus 30A and Clostridium perfringens and
      the amino acid sequences of these histidine decarboxylases and those of
      Lactobacillus buchneri and Micrococcus, oligonucleotides unique to the hdcA genes
      were synthesized and used in PCR. All histidine-decarboxylating lactic acid
      bacteria gave a signal with primer set JV16HC/JV17HC in PCR. In addition to this
      primer set, CL1/CL2 and CL1/JV17HC were also useful for the detection of
      histamine-forming Leuconostoc aenos strains in PCR. The 150 base pair
      amplification product of the decarboxylating Leuc. aenos strain generated with
      primer set CL1/CL2 was sequenced. Alignment studies showed a high degree of
      relatedness among the hdcA gene products of Gram-positive bacteria. The
      amplification products of the hdcA genes from Lac. buchneri and Leuct. aenos were
      used to serve as a DNA probe in hybridization studies. All histidine
      decarboxylating lactic acid bacteria gave a hybridization signal with the DNA
      probes. In hybridization only one false-positive signal with a Lactobacillus
      lindneri strain was observed, which was anticipated to contain a truncated hdcA
      gene. In addition to these DNA probe tests, a simple and reliable activity test
      is presented, which can be used during starter selection to test strains for
      histidine decarboxylase activity.

PMID- 7730208
TI  - Influence of ethanol and temperature on the cellular fatty acid composition of
      Zygosaccharomyces bailii spoilage yeasts.
AB  - Changes in the fatty acid profile of Zygosaccharomyces bailii strains, isolated
      from different sources, after growth at increasing concentrations of ethanol
      and/or decreasing temperatures were determined. Differences in fatty acid
      composition between Zygosaccharomyces bailii strains at standard conditions (25
      degrees C, 0% initial ethanol) were observed and could be related to ethanol
      tolerance. Zygosaccharomyces bailii strain isolated from wine showed the highest
      ethanol tolerance in relation to growth rate. Surprisingly, an increase in
      ethanol concentration or a decrease in growth temperature caused a decrease in
      the degree of unsaturation of total cellular fatty acids. On the other hand, the
      mean chain length increased (high ethanol concentration) or decreased (low
      temperature) depending on the stress factor. When both stress situations (high
      ethanol concentration and low temperature) were present at the same time, the
      degree of unsaturation remained approximately constant. With decreasing
      temperatures, the C16/C18 ratio increased in studies of initial ethanol content
      below 5%, and above 5% ethanol, decreased.

PMID- 7730209
TI  - [The dermal connective tissue of leprosy patients. Part 1. The elastic fibers and
      the skin appendages].
AB  - Leprosy patients who are keeping long quiescent conditions show some
      characteristic changes clinically on their skins. The elastic fibers and skin
      appendages are important factors for the peculiar skin characters. We calculated
      the collagen and elastic fibers in the limbs and redundant facial skins of
      leprosy patients by automated computerized image analyser. Histopathological
      studies of these samples were also done. All cases were over sixty years old and
      many of them were in quiescent conditions. The control cases were taken from the
      same parts of age matched normal skins. We found the dermal thickness of lower
      legs of patients was significantly lower than that of controls. The amount of
      collagen fibers had tendensy of decrease accompanied with decreased dermal
      thickness, but the elastic fibers of leprosy patients did not show the same
      tendensy. In the patients' skin, the elastic fibers arranged irregularly,
      sometimes fragmented and focally coagressed. Skin appendages were greatly
      decreased and intraepidermal pores of sweat ducts were almost disappeared, but
      many sweat glands have survived. Of the facial skins, only 1 case showed a
      compatible feature with solar elastosis. We concluded that the dermal elastic
      fibers of leprosy patients had characteristic features. The types of leprosy,
      duration periods of active condition, destructed dermal structures, all these
      factors were suspected to have some relations with these phenomena.

PMID- 7730210
TI  - Down regulation of Ia expression in macrophages following incubation with
      mycobacteria.
AB  - Macrophages are known to release cytokines in response to various kinds of
      stimulators. In the present study, peritoneal macrophages from C3H/He or C3H/HeJ
      mice were incubated in vitro with heat-killed M. lepraemurium, M. intracellulare
      or M. gordonare for 3 days followed by harvest culture supernatant to analyze
      cytokine activities. It, therefore, seems that macrophages phagocytizing these
      mycobacteria, released interleukin-1 (IL-1) and tumor necrosis factor (TNF) in
      culture media. The amount of release was dose dependent on mycobacteria employed.
      In addition, macrophages, as already have reported elsewhere, treated with IFN
      for 2 to 3 days showed enhanced expression of surface Ia; although the expression
      was inhibited if the cells phagocytized mycobacteria. Similarly, the reduced
      expression of Ia was observed in peritoneal macrophages from MRL/lpr mice after 3
      day-culture with mycobacteria in vitro. More importantly, in the presence of the
      supernatant obtained from macrophages incubated with mycobacteria, IFN gamma
      treated normal macrophages exhibited suppressed expression of Ia. These results
      demonstrate that cytokine release and reduced expression of surface Ia in
      macrophages are simultaneous phenomena after phagocytosis of mycobacteria.
      Suppression of Ia may be in part induced by Ia suppressive factor(s) released
      from mycobacterium-phagocytized macrophages.

PMID- 7730211
TI  - Clofazimine-mediated augmentation of LPS-induced tumor necrosis factor production
      in macrophages.
AB  - Tumor necrosis factor (TNF) exerts multiple biological activities including
      immune response. It is also believed to play an important role in anti-bacterial
      response. In this study in vitro, we observed augmentation of LPS-induced TNF
      production from mouse macrophages by clofazimine treatment. Rifampicin, however,
      did not indicate such an activity. Clofazimine itself, on the other hand, did not
      have any TNF-inducing activity. Clofazimine is a well known anti-leprosy drug; in
      addition, from the results obtained here, this drug could induce anti-M. leprae
      response of host by way of the augmented immune response by enhanced cytokine
      production from macrophages.

PMID- 7730212
TI  - Paucibacillary leprosy patients treated with multidrug therapy four years
      experience (1988 to 1991) in Bangladesh.
AB  - Two hundred and fifty paucibacillary (PB) leprosy patients were treated with WHO
      recommended multidrug therapy (MDT) and followed up them for four years. The
      paucibacillary MDT regimen (PBR) was well accepted and tolerated by the patients.
      Clinical regression was attained in 60% patients after 6 doses of PBR. Reversal
      reaction occurred in 14% cases and relapse were found in 1.6% cases 18-24 months
      after completing the treatment. The incidence of reversal reaction was high in
      patients with more than 2 thickened nerve trunks associated with more than 5
      patches.

PMID- 7730213
TI  - [Effect of chloroform on the extracting efficiency of adenosine tri-phosphate
      (ATP) from the cells of Mycobacterium leprae].
AB  - Effect of chloroform on the extraction of ATP from the cells of Mycobacterium
      leprae was investigated. The results demonstrate that the yields of ATP from the
      resting cells of M. leprae were much more higher when 100mM Tris-EDTA was added
      to the procedure than that of the routine method. The amounts of ATP extracted
      from the cells of M. leprae incubated either in 10% calf serum-buffer (pH 7) or
      10% calf serum-2% glycerin-Dubos medium at 30 degrees C gradually increased with
      time of incubation when chloroform and 100mM-Tris-EDTA were used for extraction
      of ATP, whereas no increase and periodical decrease of ATP were observed when
      Tris-EDTA only without chloroform was used in the procedure of ATP extraction.
      Therefore, it is noted that the use of chloroform and 100mM-Tris EDTA is
      indispensable for extraction of ATP from the cells of M. leprae.

PMID- 7730214
TI  - Prophylactic efficacy of aerosolized liposomal (AmBisome) and non-liposomal
      (Fungizone) amphotericin B in murine pulmonary aspergillosis.
AB  - Pulmonary aspergillosis is a serious opportunistic disease in patients with
      immune suppression. Prophylactic measures would be highly beneficial because
      treatment often fails after infection occurs. The principle objective of this
      study was to evaluate the prophylactic efficacy of aerosolized liposomal
      (AmBisome) and non-liposomal (Fungizone) amphotericin B in a murine model.
      Immunocompromised mice were treated prophylactically for 3 days with AmBisome or
      Fungizone using a small particle aerosol generator. Intranasal challenge was with
      a high (10(8)), medium (10(7)), or low (10(6)) level of Aspergillus fumigatus
      spores. AmBisome nebulized more uniformly, resulting in very consistent chamber
      air concentrations. Total dose, however, was nearly the same for each
      formulation. Survival was prolonged in animals treated with both formulations at
      the 10(8) and 10(7) challenge levels. Quantitative lung cultures showed that
      organisms were completely cleared from the lungs in the low challenged group,
      with both formulations, whereas the high challenge proved overwhelming for both
      formulations. With the middle challenge, however, AmBisome cleared 80% of the
      lungs, whereas Fungizone cleared none. Lung drug retention of AmBisome treated
      animals was more than eight times higher than Fungizone at the time of challenge.
      BUN and creatinine values in animals treated with both formulations were not
      elevated. These results suggest that AmBisome is more effective than Fungizone
      when given as a prophylactic aerosol in this model.

PMID- 7730215
TI  - Characterisation of a tet(M)-carrying plasmid from Neisseria meningitidis.

PMID- 7730216
TI  - Additive effect of clarithromycin combined with 14-hydroxy clarithromycin,
      erythromycin, amoxycillin, metronidazole or omeprazole against Helicobacter
      pylori.
AB  - The in-vitro activities of clarithromycin, 14-OH clarithromycin, erythromycin,
      amoxycillin, metronidazole and omeprazole against Helicobacter pylori were
      determined at pH 7.2 and 5.5. At pH 5.5 the activities of clarithromycin and
      erythromycin decreased approximately 16 times while 14-OH clarithromycin was less
      influenced. Chequerboard titration indicated that the combined activity of
      clarithromycin and the other compounds was additive.

PMID- 7730217
TI  - Serotypes and antimicrobial susceptibility of Haemophilus influenzae.
AB  - During a one year prospective study of Haemophilus influenzae infections in
      patients treated in hospitals in the metropolitan area of Cape Town. H.
      influenzae type b accounted for 81.7% of 126 invasive isolates, whereas 86.1% of
      the 280 non-invasive isolates were non-typeable. Ampicillin resistance was
      detected among 10.8% of strains of which all but one produced beta-lactamase. All
      strains were susceptible to cefotaxime as were more than 95% to chloramphenicol,
      rifampicin, tetracycline but 20.4% were resistant to co-trimoxazole and 87.2% to
      erythromycin.

PMID- 7730218
TI  - The in-vitro susceptibilities of toxigenic strains of Corynebacterium diphtheriae
      isolated in northwestern Russia and surrounding areas to ten antibiotics.
AB  - The in-vitro activities of ten antibiotics against 83 toxigenic strains of
      Corynebacterium diphtheriae recently isolated in northwestern Russia and
      surrounding areas were determined by an agar dilution method. All of the strains
      were susceptible to erythromycin, penicillin, ampicillin, cefuroxime,
      chloramphenicol, ciprofloxacin, gentamicin and tetracycline. Trimethoprim and
      rifampicin were each active against 81 isolates, the two strains resistant to the
      latter agent having been isolated from two members of the same family.

PMID- 7730219
TI  - A comparison of the accumulation of novobiocin into bacteria with its
      antibacterial properties.
AB  - The accumulation of novobiocin in bacteria has been compared with the MIC,
      inhibition of DNA biosynthesis and inhibition of the activity of isolated DNA
      gyrase for a range of species. There was a good correlation between MIC and the
      inhibition of DNA biosynthesis and DNA gyrase. Novobiocin accumulation did not
      correlate with any other parameter.

PMID- 7730220
TI  - Amoxycillin causes an enhanced uptake of metronidazole in Actinobacillus
      actinomycetemcomitans: a mechanism of synergy.
AB  - We investigated the influence of sub-inhibitory concentrations amoxycillin on
      metronidazole uptake of the metronidazole-susceptible facultative microorganism
      Actinobacillus actinomycetemcomitans. The rate of metronidazole uptake by
      bacterial cells simultaneously incubated with amoxycillin was higher than uptake
      in cells incubated with metronidazole alone. This phenomenon may explain the
      recently reported in-vitro synergic interaction between metronidazole and
      amoxycillin against A. actinomycetemcomitans.

PMID- 7730221
TI  - Synergic inhibitory activity of amphotericin-B and gamma interferon against
      intracellular Cryptococcus neoformans in murine macrophages.
AB  - Cryptococcus neoformans is responsible for pulmonary and meningal infections in
      HIV patients. The lack of effective cellular cooperation caused by the low level
      of CD4+ cells, and the resistance of C. neoformans to phagocytosis allows growth
      and persistence of the yeast in the host. We describe here an in-vitro model of
      intracellular replication of C. neoformans inside J774-A.1 macrophages, and the
      determination of the intracellular antifungal activity of amphotericin B and
      fluconazole alone or in association with IFN-gamma. The maximum inhibitory effect
      was observed with one MIC of amphotericin B and 100 or 1000 IU/mL of IFN-gamma.
      amphotericin B alone (at 1 x MIC), or either 1 x or 50 x MIC of fluconazole in
      normal or IFN-gamma activated macrophages, did not eradicate the ingested yeast.
      A potential underlying mechanism of the synergy of amphotericin B in IFN-gamma
      primed macrophages was investigated by measurement of nitrite level and by use of
      the NO synthase competitive inhibitor, NG-monomethyl L-arginine (NMMA). One MIC
      of amphotericin B was able to activate the synthesis of nitrogen reactive
      intermediates in IFN gamma-primed macrophages. NMMA treated infected macrophages
      responded less well to IFN-gamma priming, resulting in a moderate inhibition in
      subsequent amphotericin B exposure.

PMID- 7730222
TI  - Antibiotic policies in Dutch hospitals for the treatment of patients with serious
      infection.
AB  - In order to assess the guidelines available in Dutch hospitals for the treatment
      of patients with serious infection of unknown aetiology, 39 antibiotic
      formularies used in 88 hospitals were analyzed. The recommendations considered
      were those for the treatment of sepsis for which the source was not apparent or
      which originated in the urinary tract, respiratory tract or abdomen. beta-Lactam
      antibiotics (most commonly amoxycillin and cefuroxime) were the preferred agents
      for empirical therapy of infections of all types; an aminoglycoside was also
      included in the majority of regimens, irrespective of the clinical presentation.
      However, there were wide variations in the choice and dosages of the drugs
      administered. Because of the absence of local data for the susceptibilities of
      blood culture isolates, the appropriateness of the recommendations could not be
      properly evaluated.

PMID- 7730223
TI  - Paradoxical response and tolerance in a strain of Staphylococcus aureus.

PMID- 7730224
TI  - Susceptibility of Chlamydia pneumoniae to oral agents commonly used in the
      treatment of respiratory infection.

PMID- 7730225
TI  - Multiclonal emergence of ciprofloxacin-resistant clinical isolates of Escherichia
      coli and Klebsiella pneumoniae.

PMID- 7730226
TI  - Screening for extended-spectrum cephalosporin resistance in Streptococcus
      pneumoniae.

PMID- 7730227
TI  - Search for protein cross-reacting with OprD antibodies in Pseudomonas spp. and
      related species.

PMID- 7730228
TI  - Comparison of the pharmacokinetics and bioavailability of spiramycin in human
      serum and saliva.

PMID- 7730229
TI  - Fosfomycin trometamol.

PMID- 7730230
TI  - Chlamydia pneumoniae.
AB  - Chlamydia pneumoniae, a fairly recent addition to the genus Chlamydia, has been
      shown to cause community-acquired and nosocomial pneumonias, and to be a common
      infectious agent in human populations throughout the world. It has a wide variety
      of clinical presentations, and may be associated with ischaemic heart disease.
      Like other species in the genus, it is difficult to isolate by cell culture:
      clinical diagnosis therefore rests on other techniques, each of which presents
      particular problems. Those discussed in this review are cell culture, antigen
      detection by direct immunofluorescence and enzyme immunoassay, serological
      methods (exemplified by micro-immunofluorescence) and the polymerase chain
      reaction. Currently available treatments and the prospect of vaccination are also
      discussed.

PMID- 7730231
TI  - In-vitro and in-vivo activity of a new quinolone AM-1155 against Mycoplasma
      pneumoniae.
AB  - We investigated the in-vitro and in-vivo activity of a new quinolone AM-1155
      against Mycoplasma pneumoniae, and compared it with ofloxacin, ciprofloxacin,
      lomefloxacin, tosufloxacin, erythromycin and minocycline. AM-1155 was the most
      potent agent in vitro of the quinolones tested. Its pre-treatment minimal
      inhibitory concentrations for 90% of the 41 strains (MIC90) was 0.06 mg/L. In
      contrast, pre-treatment MIC90 values for ofloxacin, ciprofloxacin, lomefloxacin,
      tosufloxacin, erythromycin, and minocycline were 1, 1, 2, 0.5, 0.0156, and 0.5
      mg/L, respectively. Post-treatments MIC90s, which may reflect mycoplasmacidal
      potency, of AM-1155, ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin,
      erythromycin and minocycline were 0.125, 1, 2, 4, 0.5, 0.125 and 4 mg/L,
      respectively. In-vitro activities of antimicrobial agents were assessed in an
      experimental pulmonary infection model in Syrian golden hamsters. AM-1155 was the
      most effective agent among five antimicrobial agents (AM-1155, ofloxacin,
      tosufloxacin, erythromycin, minocycline) tested in terms of reduction in viable
      M. pneumoniae cells and in reducing macroscopic lung lesions. These results
      suggest that AM-1155 will be a useful antimicrobial agent for the treatment of M.
      pneumoniae infections.

PMID- 7730232
TI  - The effect of Triton X-100 on the in-vitro susceptibility of methicillin
      resistant Staphylococcus aureus to oxacillin.
AB  - The effect of the non-ionic detergent, Triton X-100, on the in-vitro activity of
      oxacillin against methicillin-resistant (MRSA) and methicillin-susceptible (MSSA)
      strains of Staphylococcus aureus was investigated. In the presence of Triton X
      100, the MICs of oxacillin for both MRSA and MSSA isolates were reduced; this
      enhancing effect was particularly marked for the MRSA strains. Triton X-100
      therefore counteracted the resistance to methicillin encoded by mecA. In the
      presence of oxacillin at subinhibitory concentrations, Triton X-100 induced the
      bacteriolysis of MRSA and potentiated the autolysis of these organisms. However,
      the detergent had no effect on the bacteriolytic enzyme profile or the
      susceptibility of the bacterial cell wall to bacteriolytic enzymes, nor did it
      promote the binding of oxacillin to the penicillin-binding protein (PBP) 2A. On
      the other hand, it stimulated the release from the bacteria of acylated
      lipoteichoic acid (LTA), a putative endogenous regulator of autolysins. Autolytic
      enzyme-deficient MRSA mutants were equally as sensitive as the parent strain to
      the effect of Triton X-100 on susceptibility to oxacillin. These results indicate
      that the enhanced in-vitro activity of oxacillin against MRSA in the presence of
      Triton X-100 cannot be accounted for simply by the induction of bacteriolysis
      following activation of autolytic enzymes by the detergent-stimulated release of
      LTA.

PMID- 7730233
TI  - In-vitro antibacterial activity of fusidic acid alone and in combination with
      other antibiotics against methicillin-sensitive and -resistant Staphylococcus
      aureus.
AB  - The activity of fusidic acid alone and in combination with gentamicin, oxacillin,
      rifampicin, fosfomycin and ciprofloxacin was investigated against 36 strains of
      Staphylococcus aureus. The fusidic acid MIC50 of 0.06 mg/L and MIC90 of 0.125
      mg/L were determined for 36 strains. Bactericidal activity of fusidic acid was
      confirmed. Several types of interaction were observed with other antibiotics:
      dominant effect of fusidic acid over gentamicin; synergy with rifampicin for
      three or four strains; indifference or dominance with oxacillin, indifference
      with vancomycin, indifference or dominance with fosfomycin, and indifference with
      ciprofloxacin. Antagonism was seen with only one strain, following exposure to
      fusidic acid and rifampicin.

PMID- 7730234
TI  - Role of beta-lactamase of methicillin-susceptible Staphylococcus aureus in
      resistance to first-generation oral cephems both in vitro and in vivo.
AB  - Cefaclor, among the oral cephalosporins tested, showed the largest inoculum
      effect with respect to MIC values for 61 clinical isolates of methicillin
      susceptible Staphylococcus aureus, including 39 beta-lactamase producing strains.
      These 39 strains were divided into eight type A, 29 type B or C, and two type D
      producers, by comparisons of specific activities to three substrates. Two
      producers, one each of types A and C, were further studied to investigate the
      effect of beta-lactamase on staphylococcal resistance to several beta-lactams.
      Concentrations of cefaclor and cephalexin in cultures of these strains decreased
      rapidly, whereas hydrolysis of these drugs by the purified beta-lactamases was
      moderate to low as detected by spectrophotometric assay. Cefaclor showed high
      affinities for penicillin-binding proteins 1, 2, and 3 of both beta-lactamase
      producers and their respective penicillinase-non-producing mutants. In
      experimental intraperitoneal infections in mice, cefaclor was therapeutically
      effective against both mutants, showing 50% effective doses of less than 10
      mg/kg/dose. In contrast, it was not satisfactory against the parent strains,
      requiring greater-than-10-fold increases in concentration for the same degree of
      survival. We concluded that resistance to first-generation oral cephems seen both
      in vitro and in vivo was due mainly to the beta-lactamase production.

PMID- 7730235
TI  - Decreased bactericidal activity during the period of the postantibiotic effect.
AB  - Standard and clinical strains of Staphylococcus aureus, Escherichia coli and
      Klebsiella pneumoniae were subjected to continuous exposure to beta-lactams and
      aminoglycosides during the postantibiotic effect phase induced by rifampicin or
      erythromycin (for S. aureus). A significant inhibition of bactericidal activity
      by these agents during the PAE period was observed. The degree of inhibition was
      dependent both on the class of antimicrobial agent (beta-lactams >
      aminoglycosides) and the microorganism (Gram-negative bacilli > S. aureus).

PMID- 7730236
TI  - Profiles of outer membrane proteins and lipopolysaccharide of Pseudomonas
      aeruginosa grown in the presence of sub-MICs of macrolide antibiotics and their
      relation to enhanced serum sensitivity.
AB  - We have previously reported that erythromycin at sub-inhibitory concentrations
      enhanced the serum sensitivity of some Pseudomonas aeruginosa strains. To explore
      the mechanism of this effect, we have now examined the influence of macrolide
      antibiotics on outer membrane proteins and lipopolysaccharide (LPS) of P.
      aeruginosa. The strains S-6 and PAO-1 of P. aeruginosa were used as susceptible
      and resistant strains respectively to assess enhancement of serum sensitivity by
      erythromycin. The strain S-6 became more serum-sensitive when grown on agar with
      sub-MICs of erythromycin or azithromycin, but not of josamycin, whereas no change
      was observed in the serum sensitivity of the strain PAO-1 after growth with any
      of these antibiotics. The analysis of outer membrane proteins showed that
      erythromycin treatment resulted in a reduction in the amount of the 38 kDa
      protein (OprF) and in a prominent increase of 41 kDa protein band in the strain S
      6, but not in the strain PAO-1. By an immunoblotting assay, this 41 kDa protein
      was shown to be highly reactive to the immune serum against untreated P.
      aeruginosa. LPS of the strain S-6 were examined by SDS acrylamide gel
      electrophoresis. The treatment with erythromycin or azithromycin, but not with
      josamycin, reduced the amounts of LPS species with lower molecular weights
      although the levels of LPS species with high molecular weights were similar to
      those of untreated bacteria. These results suggest that the enhanced serum
      sensitivity of P. aeruginosa by erythromycin is associated with changes in
      bacterial surface components, such as outer membrane proteins and LPS.

PMID- 7730237
TI  - Production of a plasmid mediated AmpC-like beta-lactamase by a Klebsiella
      pneumoniae septicaemia isolate.
AB  - A septicaemia Klebsiella pneumoniae isolate from Greece (Ath1) was shown to be
      resistant to third generation cephalosporins, aztreonam and cefoxitin and this
      resistance was not decreased in the presence of clavulanic acid. The gene coding
      for the resistance phenotype, associated with a beta-lactamase showing
      cephalosporinase activity and a pI of 8.6, could be transferred into Escherichia
      coli K-12 by conjugation and transformation. DNA-hybridisation showed that this
      gene was located on two different plasmids, 7.8 and 80 kb respectively. The
      larger, conjugative plasmid also carried genes coding for another beta-lactamase
      (pI 6.6) and resistance to aminoglycosides, tetracycline, chloramphenicol and
      trimethoprim. Under highly stringent conditions the gene coding for the pI 8.6
      beta-lactamase hybridised with chromosomal DNA from Citrobacter freundii OS60 but
      not from E. coli or Enterobacter cloacae. Furthermore, the restriction map of
      this beta-lactamase gene corresponded to that of ampC from C. freundii OS60. The
      regulatory ampR gene could not be detected in the plasmid DNA from the Ath1 K.
      pneumoniae by DNA hybridisation. The relationship between a plasmid-mediated
      extended spectrum beta-lactamase in a K. pneumoniae septicaemia isolate and
      chromosomal AmpC beta-lactamase from C. freundii was demonstrated.

PMID- 7730238
TI  - Detection of fosfomycin resistance by the polymerase chain reaction and Western
      blotting.
AB  - The polymerase chain reaction and Western blotting were assessed as means of
      detecting plasmid-encoded fosfomycin resistance in the hope that they might
      facilitate epidemiological studies. The results indicated good correlation
      between the two methods which are more rapid, less expensive and more sensitive
      than DNA-DNA hybridization. Both techniques could potentially be employed for the
      genotypic detection of resistance to any group of antibiotics.

PMID- 7730239
TI  - Intraphagocytic killing of gram-positive bacteria by ciprofloxacin.
AB  - The intraphagocytic killing of Staphylococcus aureus, Streptococcus pyogenes, and
      Corynebacterium group D2 by ciprofloxacin (0.1, 1 and 5 mg/L) within human
      neutrophils was determined. The organisms showed different susceptibility to
      neutrophil killing mechanisms. The neutrophils with intact and impaired (by
      phenylbutazone treatment) O2-dependent killing mechanisms were studied. The
      minimum concentrations of ciprofloxacin to kill 90% of phagocytosed bacteria
      within untreated neutrophils after 2 h were 1 mg/L for S. aureus and
      Corynebacterium group D2, and 0.1 mg/L for S. pyogenes. In contrast, exposure for
      3 h was required to achieve similar cidal effects within phenylbutazone treated
      neutrophils. Synergic interaction between ciprofloxacin and the O2-dependent
      mechanisms of phagocytes was found. The reactive oxygen metabolites produced in
      the respiratory burst did not affect the intraphagocytic activity of
      ciprofloxacin. Phenylbutazone treatment of phagocytes would be a good
      experimental model to study intraphagocytic killing by drugs in situations where
      the oxidative mechanisms of neutrophils are impaired (for example AIDS and
      chronic granulomatous disease).

PMID- 7730240
TI  - Comparative capacity of four antifungal agents to stimulate murine macrophages to
      produce tumour necrosis factor alpha: an effect that is attenuated by
      pentoxifylline, liposomal vesicles, and dexamethasone.
AB  - The efficacy and toxicity of certain antifungal agents may be related to their
      ability to induce the production of cytokines by mononuclear phagocytes. The
      capacity of incremental concentrations of fluconazole, 5-fluorocytosine (5-FC),
      amphotericin B (AmB), and liposomal AmB (LAB) to stimulate murine peritoneal and
      RAW 264.7 macrophages to secrete tumour necrosis factor alpha (TNF alpha) after
      3, 6 and 24 h incubation was assessed by L929 cytotoxic bioassay. Fluconazole
      (2.5-40 mg/L) and 5-FC (25-100 mg/L) did not have a stimulatory effect. However,
      AmB (0.25-10 mg/L) elicited TNF alpha production by macrophages. This response
      was concentration-dependent, and peak TNF alpha levels were detected between 3
      and 6 h. This effect was attenuated by incorporation of AmB into liposomal
      vesicles and by pretreating macrophages with pentoxifylline or dexamethasone. AmB
      I mg/L in combination with 1 x 10(6) cfu of Candida albicans stimulated
      peritoneal macrophages to produce similar quantities of TNF alpha as AmB alone,
      and two- to four-fold more TNF alpha than C. albicans alone. Thus, this study
      suggests that: (1) the immunomodulatory activity and toxicities of AmB, in part,
      may be attributed to the capacity of this drug to stimulate macrophages to
      secrete TNF alpha, (2) the TNF alpha that is produced by macrophages in response
      to AmB may have clinical relevance even in the face of C. albicans infection, and
      (3) the failure of fluconazole, 5-FC, and LAB to elicit a TNF alpha response may
      explain their improved side-effect profiles.

PMID- 7730241
TI  - The effect of a single oral dose of azithromycin on chlamydial infertility and
      oviduct ultrastructure in mice.
AB  - Azithromycin has been recommended for the treatment of human chlamydial genital
      tract infections because of the sustained, chlamydicidal levels of the antibiotic
      which can be achieved after a single dose. The effect of single dose azithromycin
      on the prevention or reversal of chlamydial-induced damage to the oviduct or to
      fertility was assessed in a mouse model of chlamydial salpingitis which closely
      mimics the human disease. C3H mice were treated with progesterone and then
      inoculated under the ovarian bursa with a human genital tract isolate of
      Chlamydia trachomatis, serovar F. Azithromycin at doses from 135-250 mg/kg was
      administered by oral intubation. Morphological damage to the oviduct lumen was
      assessed by scanning electron microscopy, while fertility was assessed by
      breeding experiments. Treatment of mice two or seven days after infection with
      135 mg/kg azithromycin completely reversed chlamydial-induced ultrastructural
      changes and infertility. Treatment 12 or more days after infection, at doses as
      high as 250 mg/kg, failed to prevent infertility. The onset of fertility
      correlated with the loss of ciliated epithelia from the oviduct. However, the
      regeneration of ciliated epithelia following azithromycin treatment did not
      necessarily restore tubal patency. These results, if true for women also,
      indicate the need for rapid, effective antibiotic therapy for chlamydial
      salpingitis to prevent infertility and other sequelae of tubal damage.

PMID- 7730242
TI  - The role of cardiac mitochondria in the regulation of intracellular calcium
      during ischemia and reperfusion: X-ray microanalysis using freeze-dried sections.
AB  - The calcium concentration in papillary muscles was measured by X-ray
      microanalysis in order to clarify the role played by mitochondria in
      intracellular calcium regulation during ischemia and reperfusion. Rat hearts
      perfused by the Langendorff method were rapidly frozen prior to and during
      ischemia, as well as following reperfusion. Sections prepared by
      cryoultramicrotomy were freeze-dried, carbon-coated, and analyzed in an electron
      microscope. A new freeze-drying procedure was developed, in which the
      ultrastructure was well-preserved, with sarcomeres, triads, and mitochondria
      easily recognized. Calcium accumulation into the mitochondria occurred during 30
      min ischemia (29.7 +/- 17.0 mmol/kg dry weight) and increased further after 15
      min reperfusion (157.1 +/- 104.5), the calcium concentration decreased after 60
      min reperfusion (58.1 +/- 29.0). However, the calcium concentration in the
      cytosol did not change significantly. It is thought that mitochondrial calcium
      accumulation is reversible, to a certain degree, and that the mitochondria play a
      part in intracellular calcium regulation in pathological states.

PMID- 7730244
TI  - A new methodology for non-invasive clinical assessment of cardiovascular system
      performance and of ventricular-arterial coupling during stress.
AB  - The objective of the study was to develop a non-invasive method for the
      quantitative evaluation of cardiovascular performance and ventricular-arterial
      (VA) coupling during varying physiological states. VA-coupling was represented by
      the ratio between the arterial and ventricular elastances-Ea/Ees. Approximate
      indices of the relative change of Ees and VA-coupling during stress were
      developed and tested. These indices can be evaluated directly from non-invasive
      measurements of ejection fraction values (for VA-coupling) and measurements of
      stroke volumes and systolic and diastolic arterial pressures (for Ees).
      Additional relative indices can be evaluated from these data (e.g., stroke work,
      cardiac output) to yield a complete representation of the cardiovascular response
      to stress. The present methodology was applied to assess the exercise stress
      response in healthy subjects (H, n = 8) and in patients with left ventricular
      dysfunction (n = 24). Left ventricular volumes were determined by nuclear
      angiography and arterial pressures were measured non-invasively by a new,
      validated method. Using published data obtained invasively, we found that the
      relative indices of Ees and VA-coupling showed a high correlation with the
      invasive ones (r > 0.8, P < 0.01). The patients were subgrouped by their maximal
      exercise capacitance (P2-50W, P3-75W). At rest, the two patient groups had
      similar ejection fraction values (45 +/- 15% and 48 +/- 16%), which were
      significantly different from those of the healthy subjects (66 +/- 7%, P < 0.05).
      During stress, a larger increase in stroke work and cardiac output was found in
      the healthy subjects. All three groups showed similar relative increases in Ees
      and heart rate, but relative Ea increased in P2 and decreased in H, while the
      opposite was found for the end-diastolic volume. The relative VA-coupling index
      in P2 was significantly larger than that in P3 and H (P < 0.05). The present non
      invasively based indices can be used to quantitatively monitor the individual
      cardiovascular response to stress testing or drug interventions and to evaluate
      the importance of VA-coupling in the clinical setting.

PMID- 7730243
TI  - Mechanical characteristics of tachycardia-induced left-ventricular failure as
      evaluated in isolated dog hearts.
AB  - Left ventricles of control dog hearts and dog hearts failing due to chronic
      tachycardia were examined in vivo by echocardiography for systolic function and
      size, then subsequently studied with an isolated-heart system (artificial
      perfusion, artificial loading). During 3 weeks of tachycardia (250 bt/min), area
      ejection fraction fell by 58%, while end-diastolic transverse area increased by
      56% (measurements at 120 bt/min). Judging from post-perfusion left-ventricular
      weights, the dilation occurred with no hypertrophy, raising the question whether
      the failure model may be associated with anabolic dysfunction. End-diastolic
      pressure-volume (P-V) relations occurred at higher volumes in failing chambers
      than in controls, and this was marked by increases in two indices of chamber size
      (candidate reference volumes): the volume resulting in a diastolic stress of 16
      g/cm2, and the volume at which the nearly straight, low-stiffness segment of the
      end-diastolic P-V relation meets the upward bending, high-stiffness segment.
      Developed P-V relations of failing chambers were shifted to higher volumes and to
      lower pressures, the lower pressures being due more to reduced stress-developing
      ability (contractility) than to reduced wall/cavity ratio (pressure/stress
      ratio). On average, shortening ability (normalized difference between reference
      volume and extrapolated volume-axis intercept, i.e., apparent ejection fraction
      from reference volume in absence of afterload) was not different from that of
      controls. Isovolumic pressure waves of the failing and dilated chambers were of
      almost normal duration and shape, extending further the range of conditions where
      isovolumic pressure can be predicted by fitting a model isovolumic wave function
      to the isovolumic phases of ejecting beats.

PMID- 7730245
TI  - Detection of "pathologic" prosthetic valve stenosis via exercise Doppler
      echocardiography.
AB  - To detect borderline mitral valve dysfunction in asymptomatic patients, with
      Bjork-Shiley valves, we studied the patients' hemodynamics at rest and during
      exercise by Doppler echocardiography. Supine bicycle exercise was performed by 65
      patients. The patients were divided into two groups according to the measurements
      of the exercise Doppler echocardiography: a normally functioning group (n = 45)
      and a borderline group (n = 20). The valve area at rest was 2.0 +/- 0.6, 2.1 +/-
      0.7, and 2.3 +/- 0.5 cm2 with valve sizes of 25, 27, and 29 mm, respectively, in
      the normal group and 1.9 +/- 0.5, 1.9 +/- 0.4, and 2.1 +/- 0.3 cm2 in the
      borderline group. The mitral valve area did not significantly change with
      exercise in either group. In the normal group, peak gradients increased from 9.9
      +/- 3.5, 9.7 +/- 1.1, and 9.5 +/- 1.6 mmHg with valve sizes of 25, 27, and 29 mm,
      respectively, at rest to 15.1 +/- 3.1, 14.0 +/- 3.3, and 14.8 +/- 2.6 mmHg with
      exercise. Mean gradients increased from 5.2 +/- 1.2, 5.9 +/- 1.3, and 5.8 +/- 1.8
      mmHg with valve sizes of 25, 27, and 29 mm, respectively, at rest to 8.0 +/- 2.5,
      9.1 +/- 2.0, and 8.8 +/- 1.6 mmHg with exercise. In the borderline group, peak
      gradients increased from 10.5 +/- 3.1, 10.1 +/- 2.1, and 10.8 +/- 1.7 mmHg with
      valve sizes of 25, 27, and 29 mm, respectively, at rest to 24.5 +/- 4.2, 23.6 +/-
      4.4, and 22.4 +/- 3.2 mmHg with exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730246
TI  - Time-dependent thickening of the intima in aortocoronary saphenous vein grafts:
      clinicopathological analysis of 24 patients.
AB  - The present study was undertaken to investigate histological changes in
      aortocoronary saphenous vein grafts (SVGs) and the relationship between intimal
      thickening of the SVGs and the interval after grafting. The SVGs were divided
      into five groups according to the degree of intimal thickening and associated
      luminal narrowing: minimal thickening (0%-10% stenosis), slight thickening (11%
      25% stenosis), slight-to-moderate thickening (26%-50% stenosis), moderate
      thickening (51%-75% stenosis), and severe thickening (76%-100% stenosis). SVGs
      showing minimal thickening had been implanted for 0-3 weeks, those with slight
      thickening for 2-13 weeks, those with slight-to-moderate thickening for 5-13
      weeks, those with moderate thickening for 30-52 weeks, and those with severe
      thickening for 30-83 weeks. Thickening of the intima in SVGs (intimal
      hyperplasia) was time-dependent, and began as early as 2 weeks after the graft
      surgery. The change was diffuse and concentric, and observed from an aortic root
      to a coronary site. The major cell type involved in the intimal hyperplasia was
      the smooth muscle cell.

PMID- 7730248
TI  - APICON 1995. Association of Physicians of India 50th Golden Jubilee Conference.
      Madras, 18-23 January 1995. Abstracts.

PMID- 7730247
TI  - Centrifugal and roller pumps--are there differences in coagulation and
      fibrinolysis during and after cardiopulmonary bypass?
AB  - A number of hemostatic parameters reflecting the activation of coagulation and
      fibrinolysis were investigated in a prospective study of 24 patients undergoing
      cardiopulmonary bypass (CPB) during heart surgery. The patients were randomized
      to a group in which either a roller (group 1) or a centrifugal pump (group 2) was
      used. Blood samples were taken preoperatively, at the onset of and every 20 min
      during CPB, after the administration of protamine, and 4, 20, 44, and 68 h
      postoperatively. The groups did not differ significantly in hematocrit,
      fibrinogen, factor XIII, and antithrombin III. Significant differences in favor
      of group 2 during and after CPB were found in prothrombin fragment F1 + 2,
      plasmin-antiplasmin complex (PAP), thrombin-antithrombin complex (TAT), and D
      dimer (F1 + 2 P < 0.01 after 80-min CPB, PAP P < 0.005 after 40-min CPB, TAT and
      D-dimer P < 0.05 after 100-min CPB, D-dimer and PAP P < 0.05 after protamine
      administration, TAT and F1 + 2 4 h after CPB). These findings indicate the
      activation of fibrinolysis preceding thrombin generation during cardiopulmonary
      bypass. In addition, we conclude that centrifugal blood pumping is beneficial in
      avoiding excessive activation of both coagulation and fibrinolysis.

PMID- 7730249
TI  - Electron paramagnetic resonance spectroscopic and electrochemical
      characterization of the partially purified N5
      methyltetrahydromethanopterin:coenzyme M methyltransferase from Methanosarcina
      mazei Go1.
AB  - The N5-methyltetrahydromethanopterin:coenzyme M methyltransferase is a membrane
      bound cobalamin-containing protein of Methanosarcina mazei Go1 that couples the
      methylation of coenzyme M by methyltetra-hydrosarcinopterin to the translocation
      of Na+ across the cell membrane (B. Becher, V. Muller, and G. Gottschalk, J.
      Bacteriol. 174:7656-7660, 1992). We have partially purified this enzyme and shown
      that, in addition to the cobamide, at least one iron-sulfur cluster is essential
      for the transmethylation reaction. The membrane fraction or the partly purified
      protein contains a "base-on" cobamide with a standard reduction potential (Eo')
      for the Co2+/1+ couple of -426 mV. The iron-sulfur cluster appears to be a [4Fe
      4S]2+/1+ type with an Eo' value of -215 mV. We have determined the
      methyltransferase activity at various controlled redox potentials and
      demonstrated that the enzyme activity is activated by a one-electron reduction
      with half-maximum activity occurring at -235 mV in the presence of ATP and -450
      mV in its absence. No activation was observed when ATP was replaced by other
      nucleoside triphosphates or nonhydrolyzable ATP analogs.

PMID- 7730250
TI  - Glucose transport by a mutant of Streptococcus mutans unable to accumulate sugars
      via the phosphoenolpyruvate phosphotransferase system.
AB  - Streptococcus mutans transports glucose via the phosphoenolpyruvate (PEP)
      dependent sugar phosphotransferase system (PTS). Earlier studies indicated that
      an alternate glucose transport system functions in this organism under conditions
      of high growth rates, low pH, or excess glucose. To identify this system, S.
      mutans BM71 was transformed with integration vector pDC-5 to generate a mutant,
      DC10, defective in the general PTS protein enzyme I (EI). This mutant expressed a
      defective EI that had been truncated by approximately 150 amino acids at the
      carboxyl terminus as revealed by Western blot (immunoblot) analysis with anti-EI
      antibody and Southern hybridizations with a fragment of the wild-type EI gene as
      a probe. Phosphotransfer assays utilizing 32P-PEP indicated that DC10 was
      incapable of phosphorylating HPr and EIIAMan, indicating a nonfunctional PTS.
      This was confirmed by the fact that DC10 was able to ferment glucose but not a
      variety of other PTS substrates and phosphorylated glucose with ATP and not PEP.
      Kinetic assays indicated that the non-PTS system exhibited an apparent Ks of 125
      microM for glucose and a Vmax of 0.87 nmol mg (dry weight) of cells-1 min-1.
      Sugar competition experiments with DC10 indicated that the non-PTS transport
      system had high specificity for glucose since glucose transport was not
      significantly by a 100-fold molar excess of several competing sugar substrates,
      including 2-deoxyglucose and alpha-methylglucoside. These results demonstrate
      that S. mutans possesses a glucose transport system that can function
      independently of the PEP PTS.

PMID- 7730252
TI  - Synthesis of fluoroacetate from fluoride, glycerol, and beta-hydroxypyruvate by
      Streptomyces cattleya.
AB  - Streptomyces cattleya produces fluoroacetate and 4-fluorothreonine from inorganic
      fluoride added to the culture broth. We have shown by 19F nuclear magnetic
      resonance (NMR) spectrometry that fluoroacetate is accumulated first in the
      culture broth and that accumulation of 4-fluorothreonine is next. To show
      precursors of the carbon skeleton of fluoroacetate, we carried out tracer
      experiments with various 14C- and 13C-labeled compounds. Radioactivity of [U
      14C]glucose, [U-14C]glycerol, [U-14C]serine, and [U-14C]beta-hydroxypyruvate was
      incorporated into fluoroacetate to an extent of 0.2 to 0.4%, whereas [3
      14C]pyruvate, [2,3-14C]succinate, and [U-14C]aspartate were less efficiently
      incorporated (0.04 to 0.08%). The addition of [2-13C]glycerol to the mycelium
      suspension of Streptomyces cattleya caused exclusive enrichment of the carboxyl
      carbon of fluoroacetate with 13C; about 40% of carboxyl carbon of fluoroacetate
      was labeled with 13C. We studied the radioactivity incorporation of [3-14C]-, [U
      14C]-, and [1-14C]beta-hydroxypyruvates to show that C-2 and C-3 of beta
      hydroxypyruvate are exclusively converted to the carbon skeleton of
      fluoroacetate. These results suggest that the carbon skeleton of fluoroacetate
      derives from C-1 and C-2 of glycerol through beta-hydroxypyruvate, whose hydroxyl
      group is eventually replaced by fluoride.

PMID- 7730251
TI  - Molecular characterization of a Campylobacter jejuni lipoprotein with homology to
      periplasmic siderophore-binding proteins.
AB  - A genomic library of Campylobacter jejuni (NCTC 11351) was used to identify genes
      which could confer a hemolytic phenotype to Escherichia coli. Accordingly, when
      transformants were screened on blood plates, hemolytic colonies appeared at a
      frequency of 3 x 10(-4). The gene conferring the hemolytic activity was
      identified by subcloning and was found to be responsible for the phenotype of all
      hemolytic transformants isolated. The open reading frame conferring this activity
      encodes a protein of 36,244 Da with a typical endopeptidase type II leader
      sequence. The protein is modified with palmitic acid when it is processed in E.
      coli, confirming that it is a typical lipoprotein. The deduced gene product of
      329 amino acids has significant homology to the group of solute binding proteins
      from periplasmic-binding-protein-dependent transport systems for ferric
      siderophores, including the FatB protein from Vibrio anguillarium and the FhuD
      protein from Bacillus subtilis. In particular, the protein contained the
      signature sequence for siderophore-binding proteins, suggesting that the protein
      may be the siderophore-binding protein component of an iron acquisition system of
      C. jejuni.

PMID- 7730253
TI  - Distribution of proteins similar to IIIManH and IIIManL of the Streptococcus
      salivarius phosphoenolpyruvate:mannose-glucose phosphotransferase system among
      oral and nonoral bacteria.
AB  - In Streptococcus salivarius, the phosphoenolpyruvate (PEP):mannose-glucose
      phosphotransferase system, which concomitantly transports and phosphorylates
      mannose, glucose, fructose, and 2-deoxyglucose, is composed of the general energy
      coupling proteins EI and HPr, the specific membrane-bound IIIMan, and two forms
      of a protein called IIIMan, with molecular weights of 38,900 (IIIManH) and 35,200
      (IIIManL), that are found in the cytoplasm as well as associated with the
      membrane. Several lines of evidence suggest that IIIManH and/or IIIManL are
      involved in the control of sugar metabolism. To determine whether other bacteria
      possess these proteins, we tested for their presence in 28 oral streptococcus
      strains, 3 nonoral streptococcus strains, 2 lactococcus strains, 2 enterococcus
      strains, 2 bacillus strains, 1 lactobacillus strain, Staphylococcus aureus, and
      Escherichia coli. Three approaches were used to determine whether the IIIMan
      proteins were present in these bacteria: (i) Western blot (immunoblot) analysis
      of cytoplasmic and membrane proteins, using anti-IIIManH and anti-IIIManH rabbit
      polyclonal antibodies; (ii) analysis of PEP-dependent phosphoproteins by
      polyacrylamide gel electrophoresis; and (iii) inhibition by anti-IIIMan
      antibodies of the PEP-dependent phosphorylation of 2-deoxyglucose (a mannose
      analog) by crude cellular extracts. Only the species S. salivarius and
      Streptococcus vestibularis possessed the two forms of IIIMan. Fifteen other
      streptococcal species possessed one protein with a molecular weight between
      35,200 and 38,900 that cross-reacted with both antibodies. In the case of 9
      species, a protein possessing the same electrophoretic mobility was
      phosphorylated at the expense of PEP. No such phosphoprotein, however, could be
      detected in the other six species. A III(Man)-like protein with a molecular
      weight of 35,500 was also detected in Lactobacillus casei by Western blot
      experiments as well as by PEP-dependent phosphoprotein analysis, and a protein
      with a molecular weight of 38,900 that cross-reacted with anti-III(Man)
      antibodies was detected in Lactococcus lactis. In several cases, the involvement
      of these putative III(Man) proteins in the PEP-dependent phosphorylation of 2
      deoxyglucose was substantiated by the inhibition of phosphorylation activity of
      anti-III(Man) antibodies. No proteins cross-reacting with anti-III(Man)
      antibodies were detected in enterococci, bacilli, and E. coli. In S. aureus, a
      membrane protein with a molecular weight of 50,000 reacted strongly with the
      antibodies. This protein, however, was not phosphorylated at the expense of PEP.

PMID- 7730254
TI  - Single amino acid changes in domain II of Bacillus thuringiensis CryIAb delta
      endotoxin affect irreversible binding to Manduca sexta midgut membrane vesicles.
AB  - Deletion of amino acid residues 370 to 375 (D2) and single alanine substitutions
      between residues 371 and 375 (FNIGI) of lepidopteran-active Bacillus
      thuringiensis CryIAb delta-endotoxin were constructed by site-directed
      mutagenesis techniques. All mutants, except that with the I-to-A change at
      position 373 (I373A), produced delta-endotoxin as CryIAb and were stable upon
      activation either by Manduca sexta gut enzymes or by trypsin. Mutants D2, F371A,
      and G374A lost most of the toxicity (400 times less) for M. sexta larvae, whereas
      N372A and I375A were only 2 times less toxic than CryIAb. The results of
      homologous and heterologous competition binding assays to M. sexta midgut brush
      border membrane vesicles (BBMV) revealed that the binding curves for all mutant
      toxins were similar to those for the wild-type toxin. However, a significant
      difference in irreversible binding was observed between the toxic (CryIAb, N372A,
      and I375A) and less-toxic (D2, F371A, and G374A) proteins. Only 20 to 25% of
      bound, radiolabeled CryIAb, N372A, and I375A toxins was dissociated from BBMV,
      whereas about 50 to 55% of the less-toxic mutants, D2, F371A, and G374A, was
      dissociated from their binding sites by the addition of excess nonlabeled ligand.
      Voltage clamping experiments provided further evidence that the insecticidal
      property (inhibition of short-circuit current across the M. sexta midgut) was
      directly correlated to irreversible interaction of the toxin with the BBMV. We
      have also shown that CryIAb and mutant toxins recognize 210- and 120-kDa peptides
      in ligand blotting. Our results imply that mutations in residues 370 to 375 of
      domain II of CrylAb do not affect overall binding but do affect the irreversible
      association of the toxin to the midgut columnar epithelial cells of M. sexta.

PMID- 7730255
TI  - Transcriptional regulation of the cryIVD gene operon from Bacillus thuringiensis
      subsp. israelensis.
AB  - The CryIVD protein is involved in the overall toxicity of the Bacillus
      thuringiensis subsp. israelensis parasporal inclusions and is one of the four
      major components of the crystals. Determination of the DNA sequence indicated
      that the cryIVD gene is the second gene of an operon which includes three genes.
      The first one encodes a 19-kDa polypeptide and has sequence homology with the
      orf1 gene of the Bacillus thuringiensis cryIIA and cryIIC operons. The second and
      third genes have already been identified and encode the CryIVD crystal protein
      and the P20 polypeptide, respectively. The promoter region was located by
      deletion analysis, and the 5' end of the mRNA was determined by primer extension
      mapping. Transcription of the cryIVD gene in B. thuringiensis subsp. israelensis
      strains is induced 9 h after the beginning of sporulation. Sequence analysis
      indicated two potential promoters, a strong one and a weak one, recognized
      respectively by the RNA polymerase associated with the sigma 35 or the sigma 28
      factor of B. thuringiensis (sigma E and sigma K of Bacillus subtilis,
      respectively). Transcriptional lacZ fusion integrated in single copy into the
      chromosome of various B. subtilis sporulation mutants confirmed the sigma E
      dependence of cryIVD gene transcription.

PMID- 7730256
TI  - Evidence for two evolutionary lineages of highly pathogenic Yersinia species.
AB  - Sensitivity to Yersinia pestis bacteriocin pesticin correlates with the existence
      of two groups of human pathogenic yersiniae, mouse lethal and mouse nonlethal.
      The presence of the outer membrane pesticin receptor (FyuA) in mouse-lethal
      yersiniae is a prerequisite for pesticin sensitivity. Genes that code for FyuA
      (fyuA) were identified and sequenced from pesticin-sensitive bacteria, including
      Y. enterocolitica biotype 1B (serotypes O8; O13, O20, and O21), Y.
      pseudotuberculosis serotype O1, Y. pestis, two known pesticin-sensitive
      Escherichia coli isolates (E. coli Phi and E. coli CA42), and two newly
      discovered pesticin-sensitive isolates, E. coli K49 and K235. A 2,318-bp fyuA
      sequence was shown to be highly conserved in all pesticin-sensitive bacteria,
      including E. coli strains (DNA sequence homology was 98.5 to 99.9%). The same
      degree of DNA homology (97.8 to 100%) was established for the sequenced 276-bp
      fragment of the irp2 gene that encodes high-molecular-weight protein 2, which is
      also thought to be involved in the expression of virulence by Yersinia species.
      Highly conserved irp2 was also found in all pesticin-sensitive E. coli strains.
      On the basis of the fyuA and irp2 sequence homologies, two evolutionary groups of
      highly pathogenic Yersinia species can be established. One group includes Y.
      enterocolitica biotype 1B strains, while the second includes Y. pestis, Y.
      pseudotuberculosis serotype O1, and irp2-positive Y. pseudotuberculosis serotype
      O3 strains. E. coli Phi, CA42, K49, and K235 belong to the second group. The
      possible proximity of these two iron-regulated genes (fyuA and irp2), as well as
      their high levels of sequence conservation and similar G+C contents (56.2 and
      59.8 mol%), leads to the assumption that these two genes may represent part of an
      unstable pathogenicity island that has been acquired by pesticin-sensitive
      bacteria as a result of a horizontal transfer.

PMID- 7730257
TI  - The fliA gene encoding sigma 28 in Yersinia enterocolitica.
AB  - Yersinia enterocolitica is an enterobacterium responsible for gastrointestinal
      syndromes. Its pathogenicity depends on the presence of the 70-kb pYV plasmid,
      which directs Yop secretion. The Yop secretion machinery, consisting of the YscA
      U and LcrD proteins, presents some structural similarity with the flagellum
      assembly machinery characterized in other bacteria. Flagellum assembly requires
      sigma 28, an alternative sigma factor. The region upstream of the lcrD gene
      resembles promoters recognized by sigma 28, suggesting that the similarity
      between Yop secretion and flagellum assembly could extend to their regulation.
      The chromosome of Y. enterocolitica also contains pathogenicity determinants such
      as myfA, which encodes the Myf antigen subunit. The promoter region of myfA also
      resembles promoters recognized by sigma 28. In an attempt to clarify the role of
      sigma 28 in the expression of lcrD, myfA, and flagellar genes, we cloned,
      sequenced, and mutagenized the fliA gene encoding the sigma 28 homolog in Y.
      enterocolitica. As is the case in other bacteria, fliA was required for motility.
      However, it was involved neither in fibrilla synthesis nor in Yop secretion. The
      fliA mutant allowed us to monitor the role of motility in pathogenesis. At least
      in the mouse model, motility seemed not to be required for Y. enterocolitica
      pathogenesis.

PMID- 7730258
TI  - Lethal oxidative damage and mutagenesis are generated by iron in delta fur
      mutants of Escherichia coli: protective role of superoxide dismutase.
AB  - The Escherichia coli Fur protein, with its iron(II) cofactor, represses iron
      assimilation and manganese superoxide dismutase (MnSOD) genes, thus coupling iron
      metabolism to protection against oxygen toxicity. Iron assimilation is triggered
      by iron starvation in wild-type cells and is constitutive in fur mutants. We show
      that iron metabolism deregulation in fur mutants produces an iron overload,
      leading to oxidative stress and DNA damage including lethal and mutagenic
      lesions. fur recA mutants were not viable under aerobic conditions and died after
      a shift from anaerobiosis to aerobiosis. Reduction of the intracellular iron
      concentration by an iron chelator (ferrozine), by inhibition of ferric iron
      transport (tonB mutants), or by overexpression of the iron storage ferritin H
      like (FTN) protein eliminated oxygen sensitivity. Hydroxyl radical scavengers
      dimethyl sulfoxide and thiourea also provided protection. Functional
      recombinational repair was necessary for protection, but SOS induction was not
      involved. Oxygen-dependent spontaneous mutagenesis was significantly increased in
      fur mutants. Similarly, SOD deficiency rendered sodA sodB recA mutants nonviable
      under aerobic conditions. Lethality was suppressed by tonB mutations but not by
      iron chelation or overexpression of FTN. Thus, superoxide-mediated iron reduction
      was responsible for oxygen sensitivity. Furthermore, overexpression of SOD
      partially protected fur recA mutants. We propose that a transient iron overload,
      which could potentially generate oxidative stress, occurs in wild-type cells on
      return to normal growth conditions following iron starvation, with the coupling
      between iron and MnSOD regulation helping the cells cope.

PMID- 7730259
TI  - Sequences determining the cytoplasmic localization of a chemoreceptor domain.
AB  - The Escherichia coli serine chemoreceptor (Tsr) is a protein with a simple
      topology consisting of two membrane-spanning sequences (TM1 and TM2) separating a
      large periplasmic domain from N-terminal and C-terminal cytoplasmic regions. We
      analyzed the contributions of several sequence elements to the cytoplasmic
      localization of the C-terminal domain by using chemoreceptor-alkaline phosphatase
      gene fusions. The principal findings were as follows. (i) The cytoplasmic
      localization of the C-terminal domain depended on TM2 but was quite tolerant of
      mutations partially deleting or introducing charged residues into the sequence.
      (ii) The basal level of C-terminal domain export was significantly higher in
      proteins with the wild-type periplasmic domain than in derivatives with a
      shortened periplasmic domain, suggesting that the large size of the wild-type
      domain promotes partial membrane misinsertion. (iii) The membrane insertion of
      deletion derivatives with a single spanning segment (TM1 or TM2) could be
      controlled by either an adjacent positively charged sequence or an adjacent
      amphipathic sequence. The results provide evidence that the generation of the Tsr
      membrane topology is an overdetermined process directed by an interplay of
      sequences promoting and opposing establishment of the normal structure.

PMID- 7730260
TI  - A mutation in the Neisseria gonorrhoeae rfaD homolog results in altered
      lipooligosaccharide expression.
AB  - The gonococcal lsi-6 locus was cloned and shown by DNA sequence analysis to have
      homology with the E. coli rfaD gene, which encodes ADP-L-glycero-D-mannoheptose
      epimerase. This enzyme is involved in the biosynthesis of the lipopolysaccharide
      precursor ADP-L-glycero-D-mannoheptose. A site-directed frameshift mutation in
      lsi-6 was constructed by PCR amplification and introduced into the chromosome of
      Neisseria gonorrhoeae MS11 P+ by transformation. The lipooligosaccharides (LOS)
      of mutant and parental strains were characterized by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). The lsi-6 mutant produced LOS
      components with apparent molecular masses of 2.6 and 3.6 kDa as compared with a
      3.6-kDa band of the MS11 P+ strain. The parental LOS phenotype was expressed when
      a revertant was constructed by transformation of the cloned wild-type gene into
      the lsi-6 mutant. The immunoreactivity of LOS from parental and constructed
      strains was examined by SDS-PAGE and Western blotting. Only the parental and
      reconstructed wild-type strains produced a 3.6-kDa LOS component that reacted
      with monoclonal antibody 2-1-L8. These results suggest that the lsi-6 locus is
      involved in gonococcal LOS biosynthesis and that the nonreactive mutant 3.6-kDa
      LOS component contains a conformational change or altered saccharide composition
      that interferes with immunoreactivity.

PMID- 7730261
TI  - EmrR is a negative regulator of the Escherichia coli multidrug resistance pump
      EmrAB.
AB  - The emrAB locus of Escherichia coli encodes a multidrug resistance pump that
      protects the cell from several chemically unrelated antimicrobial agents, e.g.,
      the protonophores carbonyl cyanide m-chlorophenylhydrazone (CCCP) and
      tetrachlorosalicyl anilide and the antibiotics nalidixic acid and thiolactomycin.
      The mprA gene is located immediately upstream of this locus and was shown to be a
      repressor of microcin biosynthesis (I. del Castillo, J. M. Gomez, and F. Moreno,
      J. Bacteriol. 173:3924-3929, 1991). There is a putative transcriptional
      terminator sequence between the mprA and emrA genes. To locate the emr promoter,
      single-copy lacZ operon fusions containing different regions of the emr locus
      were made. Only fusions containing the mprA promoter region were expressed. mprA
      is thus the first gene of the operon, and we propose that it be renamed emrR.
      Overproduction of the EmrR protein (with a multicopy vector containing the cloned
      emrR gene) suppressed transcription of the emr locus. A mutation in the emrR gene
      led to overexpression of the EmrAB pump and increased resistance to antimicrobial
      agents. CCCP, nalidixic acid, and a number of other structurally unrelated
      chemicals induced expression of the emr genes, and the induction required EmrR.
      We conclude that emrRAB genes constitute an operon and that EmrR serves as a
      negative regulator of this operon. Some of the chemicals that induce the pump
      serve as its substrates, suggesting that their extrusion is the natural function
      of the pump.

PMID- 7730262
TI  - Transcriptional control of the nuo operon which encodes the energy-conserving
      NADH dehydrogenase of Salmonella typhimurium.
AB  - The 14 nuo genes encode the subunits of the type I (energy-conserving) NADH
      dehydrogenase, a key component of the respiratory chain. Salmonella typhimurium,
      like Escherichia coli, has two enzymes that can oxidize NADH and transfer
      electrons to ubiquinone, but only the type I enzyme translocates protons across
      the membrane to generate a proton motive force. Cells with the type I enzyme are
      energetically more efficient; the role of the type II enzyme (encoded by ndh) is
      not established, but it may function like a relief valve to allow more rapid NADH
      recycling. Here, we have investigated transcription of the nuo gene cluster,
      primarily in S. typhimurium. Studies with polar insertion mutants demonstrate
      that these genes are arranged as a single, large operon that is expressed from a
      complex promoter region upstream of nuoA. The DNA sequence of the promoter region
      was determined, and primer extension analysis of nuo transcripts was used to map
      four major RNA 5' ends to this region. A set of lac operon fusions to various DNA
      segments from the nuo promoter region was also constructed. Analysis of these
      fusions confirmed the presence of at least two nuo promoters. Mutations in the
      global regulatory genes arcA, oxrA (fnr), crp, cya, and katF were tested for
      effects on expression of the nuo operon. However, none of the mutations tested
      had a large effect on expression of type I NADH dehydrogenase.

PMID- 7730263
TI  - Hydroxyl radical footprints and half-site arrangements of binding sites for the
      CysB transcriptional activator of Salmonella typhimurium.
AB  - CysB is a transcriptional activator for the cysteine regulon and negatively
      autoregulates its own gene, cysB. Transcription activation also requires an
      inducer, N-acetyl-L-serine. CysB is known to bind to activation sites just
      upstream of the -35 regions of the positively regulated cysJIH, cysK, and cysP
      promoters and to a repressor site centered at about +1 in the cysB promoter.
      Additional accessory sites have been found in positively regulated promoters. The
      hydroxyl radical footprinting experiments reported here indicate that the
      activation sites CBS-J1, CBS-K1, and CBS-P1 in the cysJIH, cysK, and cysP
      promoters are composed of two convergently oriented 19-bp half-sites separated by
      1 or 2 bp. N-Acetyl-L-serine stimulates binding to these sites as well as to the
      accessory sites CBS-J2 and CBS-P2, both of which share a similar topology with
      activation sites. A second topology is found in the accessory site CBS-K2 and the
      repressor site CBS-B, which contain divergently oriented 19-bp half-sites
      separated by one or two helical turns. N-Acetyl-L-serine inhibits binding to
      these two sites. A third topology is present in the cysK and cysP promoters,
      where an additional half-site is oriented toward the activation site and
      separated from it by one helical turn. Here, CysB binds to all three half-sites,
      bending the DNA, and N-acetyl-L-serine decreases the extent of bending. The
      marked dissimilarities of these half-site arrangements and of their responses to
      N-acetyl-L-serine suggest that CysB, a homotetramer, binds to them with different
      combinations of subunits.

PMID- 7730264
TI  - Comparison studies of dinitrogenase reductase ADP-ribosyl
      transferase/dinitrogenase reductase activating glycohydrolase regulatory systems
      in Rhodospirillum rubrum and Azospirillum brasilense.
AB  - Reversible ADP ribosylation of dinitrogenase reductase, catalyzed by the
      dinitrogenase reductase ADP-ribosyl transferase (DRAT)/dinitrogenase reductase
      activating glycohydrolase (DRAG) regulatory system, has been characterized in
      both Rhodospirillum rubrum and Azospirillum brasilense. Although the general
      functions of DRAT and DRAG are very similar in these two organisms, there are a
      number of interesting differences, e.g., in the timing and extent of the
      regulatory response to different stimuli. In this work, the basis of these
      differences has been studied by the heterologous expression of either draTG or
      nifH from A. brasilense in R. rubrum mutants that lack these genes, as well as
      the expression of draTG from R. rubrum in an A. brasilense draTG mutant. In
      general, these hybrid strains respond to stimuli in a manner similar to that of
      the wild-type parent of the recipient strain rather than the wild-type source of
      the introduced genes. These results suggest that the differences seen in the
      regulatory response in these organisms are not primarily a result of different
      properties of DRAT, DRAG, or dinitrogenase reductase. Instead, the differences
      are likely the result of different signal pathways that regulate DRAG and DRAT
      activities in these two organisms. Our results also suggest that draT and draG
      are cotranscribed in A. brasilense.

PMID- 7730265
TI  - Molecular cloning of the plasma membrane H(+)-ATPase from Kluyveromyces lactis: a
      single nucleotide substitution in the gene confers ethidium bromide resistance
      and deficiency in K+ uptake.
AB  - A Kluyveromyces lactis strain resistant to ethidium bromide and deficient in
      potassium uptake was isolated. Studies on the proton-pumping activity of the
      mutant strain showed that a decreased H(+)-ATPase specific activity was
      responsible for the observed phenotypes. The putative K. lactis PMA1 gene
      encoding the plasma membrane H(+)-ATPase was cloned by its ability to relieve the
      potassium transport defect of this mutant and by reversing its resistance to
      ethidium bromide. Its deduced amino acid sequence predicts a protein 899 residues
      long that is structurally colinear in its full length to H(+)-ATPases cloned from
      different yeasts, except for the presence of a variable N-terminal domain. By PCR
      mediated amplification, we identified a transition from G to A that rendered the
      substitution of the fully conserved methionine at position 699 by isoleucine. We
      attribute to this amino acid change the low capacity of the mutant H(+)-ATPase to
      pump out protons.

PMID- 7730266
TI  - High-resolution alignment of a 1-megabase-long genome region of three strains of
      Rhodobacter capsulatus.
AB  - A detailed restriction map of the genome of Rhodobacter capsulatus SB1003 was
      constructed recently by using an ordered set of overlapping cosmids. Pulsed-field
      gel electrophoresis-generated restriction patterns of the chromosomes of 14 other
      R. capsulatus strains were compared. Two of them, St. Louis and 2.3.1, were
      chosen for high-resolution alignment of their genomes with that of SB1003. A 1-Mb
      segment of the R. capsulatus SB1003 cosmid set was used as a source of ordered
      probes to group cosmids from the other strains. Selected cosmids were linked into
      one 800-kb contig and two smaller contigs of 100 kb each. EcoRV and BamHI
      restriction maps of the newly ordered cosmids were constructed by using lambda
      terminase. Long-range gene order in the new strains was mainly conserved for the
      regions studied. However, one large genome rearrangement inverted a 470-kb DNA
      fragment of the St. Louis strain between the rrnA and rrnB operons. A 50-kb
      deletion covering three SB1003 probes was found in strain 2.3.1 near rrnB.
      Conservation of about 50% of the positions of restriction sites in all these
      strains and nearly 80% for the pair 2.3.1- St. Louis made it possible to produce
      high-resolution alignment of the contiguous 800-kb genome segment. Ten deletions
      of 2 to 27 kb, one 30-kb inversion, and three translocations were found in this
      region. Strong clustering of the positions of polymorphic restriction sites was
      observed. For a 50-kb size interval, two patterns of the distribution of
      restriction sites were found, one with about 90% and the other with 5 to 30%
      conservation of sites. This structure may be explained by independent acquisition
      of these divergent regions from other Rhodobacter strains.

PMID- 7730267
TI  - Temperature tolerance of hydrogenase expression in Alcaligenes eutrophus is
      conferred by a single amino acid exchange in the transcriptional activator HoxA.
AB  - Expression of the soluble (SH) and membrane-bound (MBH) hydrogenases in the
      facultatively lithoautotrophic bacterium Alcaligenes eutrophus is dependent on
      the transcriptional activator HoxA and the alternative sigma factor sigma 54.
      Deletion analysis revealed that a region 170 bp upstream of the transcriptional
      start of the SH operon is necessary for high-level promoter activity. Mobility
      shift assays with DNA fragments containing the SH upstream region and purified
      beta-galactosidase-HoxA fusion protein isolated from Escherichia coli or
      authentic HoxA isolated by immunoaffinity chromatography from A. eutrophus failed
      to detect specific binding. In contrast, A. eutrophus extracts enriched for HoxA
      by heparin-Sepharose chromatography and ammonium sulfate fractionation produced a
      weak but discrete shift in the mobility of the target DNA. This effect was not
      observed with comparable extracts prepared from hoxA mutants. A similar
      experiment using antibodies against HoxA confirmed that HoxA was responsible for
      the observed mobility shift. Extracts prepared from a temperature-tolerant mutant
      of A. eutrophus gave a stronger retardation than did those from the wild type.
      Unlike the wild type, the hox(Tr) mutant is able to grow with hydrogen at
      temperatures above 33 degrees C because of a mutation in the regulatory gene
      hoxA. In this paper, we show that a single amino acid substitution (Gly-468-
      >Val) in the C-terminal part of HoxA is responsible for temperature tolerance.
      The SH upstream region also contains sequence motifs resembling the E. coli
      integration host factor (IHF) binding site, and purified E. coli IHF protein
      shifted the corresponding indicator fragment.

PMID- 7730268
TI  - Partition of P1 plasmids in Escherichia coli mukB chromosomal partition mutants.
AB  - The partition system of the low-copy-number plasmid/prophage of bacteriophage P1
      encodes two proteins, ParA and ParB, and contains a DNA site called parS. ParB
      and the Escherichia coli protein IHF bind to parS to form the partition complex,
      in which parS is wrapped around ParB and IHF in a precise three-dimensional
      conformation. Partition can be thought of as a positioning reaction; the plasmid
      encoded components ensure that at least one copy of the plasmid is positioned
      within each new daughter cell. We have used an E. coli chromosomal partition
      mutant to test whether this positioning is mediated by direct plasmid-chromosomal
      attachment, for example, by pairing of the partition complex that forms at parS
      with a bacterial attachment site. The E. coli MukB protein is required for proper
      chromosomal positioning, so that mukB mutants generate some cells without
      chromosomes (anucleate cells) at each cell division. We analyzed the plasmid
      distribution in nucleate and anucleate mukB cells. We found that P1 plasmids are
      stable in mukB mutants and that they partition into both nucleate and anucleate
      cells. This indicates that the P1 partition complex is not used to pair plasmids
      with the host chromosome and that P1 plasmids must be responsible for their own
      proper cellular localization, presumably through host-plasmid protein-protein
      interactions.

PMID- 7730269
TI  - Envelope structure of four gliding filamentous cyanobacteria.
AB  - The cell walls of four gliding filamentous Oscillatoriaceae species comprising
      three different genera were studied by freeze substitution, freeze fracturing,
      and negative staining. In all species, the multilayered gram-negative cell wall
      is covered with a complex external double layer. The first layer is a tetragonal
      crystalline S-layer anchored on the outer membrane. The second array is formed by
      parallel, helically arranged surface fibrils with diameters of 8 to 12 nm. These
      fibrils have a serrated appearance in cross sections. In all cases, the
      orientation of the surface fibrils correlates with the sense of revolution of the
      filaments during gliding, i.e., clockwise in both Phormidium strains and
      counterclockwise in Oscillatoria princeps and Lyngbya aeruginosa. The lack of
      longitudinal corrugations or contractions of the surface fibrils and the
      identical appearances of motile and nonmotile filaments suggest that this
      structure plays a passive screw thread role in gliding. It is hypothesized that
      the necessary propulsive force is generated by shear forces between the surface
      fibrils and the continuing flow of secreted extracellular slime. Furthermore, the
      so-called junctional pores seem to be the extrusion sites of the slime. In motile
      cells, these pores exhibit a different staining behavior than that seen in
      nonmotile ones. In the former, the channels of the pores are filled with electron
      dense material, whereas in the latter, the channels appear comparatively empty,
      highly contrasting the peptidoglycan. Finally, the presence of regular surface
      structures in other gliding prokaryotes is considered an indication that
      comparable structures are general features of the cell walls of gliding microbes.

PMID- 7730270
TI  - Expression and characterization of Campylobacter jejuni benzoylglycine
      amidohydrolase (Hippuricase) gene in Escherichia coli.
AB  - The basis for the difference between Campylobacter jejuni and Campylobacter coli
      is the presence and expression of the N-benzoylglycine amidohydrolase
      (hippuricase) gene only in C. jejuni. A pBR322 recombinant clone (pHIP-O) of C.
      jejuni TGH9011 capable of converting hippuric acid into benzoic acid and glycine,
      the hallmark of hippuricase activity, was characterized and sequenced. The
      hippuricase gene (hipO) was identified by use of deletion subclones and
      insertional inactivation. The transcription start point of the hippuricase gene
      was determined by primer extension analysis. A hippuricase-specific gene fragment
      was used to determine the presence of the gene in Campylobacter species. Maxicell
      analysis of recombinant plasmid pHIP-O by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis demonstrated the production of a 42-kDa protein corresponding
      to the HipO gene product, in excellent agreement with the predicted molecular
      mass of the protein.

PMID- 7730271
TI  - Salt stress is an environmental signal affecting degradative enzyme synthesis in
      Bacillus subtilis.
AB  - Growth under conditions of salt stress has important effects on the synthesis of
      degradative enzymes in Bacillus subtilis. Salt stress strongly stimulates the
      expression of sacB, encoding levansucrase (about ninefold), and downregulates the
      expression of aprE, encoding alkaline protease (about sixfold). It is suggested
      that the DegS-DegU two-component system is involved in sensing salt stress.
      Moreover, it has been shown that the level of sacB expression strongly depends on
      the growth conditions; its expression level is about eightfold higher in cells
      grown on agar plates than in cells grown in liquid medium.

PMID- 7730272
TI  - Characterization of a genetic locus essential for maltose-maltotriose utilization
      in Staphylococcus xylosus.
AB  - A genetic locus from Staphylococcus xylosus involved in maltose-maltotriose
      utilization has been characterized. The chromosomal region was identified by
      screening a genomic library of S. xylosus in Escherichia coli for sucrose
      hydrolase activity. Nucleotide sequence analysis yielded two open reading frames
      (malR and malA) encoding proteins of 37.7 and 62.5 kDa, respectively. MalR was
      found to be homologous to the LacI-GalR family of transcriptional regulators, and
      MalA showed high similarity to yeast alpha-1,4-glucosidases and bacterial alpha
      1,6-glucosidases. Inactivation of malA in the genome of S. xylosus led to a
      maltose-maltotriose-negative phenotype. In cell extracts of the mutant, virtually
      no glucose release from maltose and short maltodextrins was detectable.
      Inactivation of malA in a sucrose-6-phosphate hydrolase-deficient S. xylosus
      strain resulted in the complete loss of the residual sucrose hydrolase activity.
      The MalA enzyme has a clear preference for maltose but is also able to release
      glucose from short maltosaccharides. It cannot cleave isomaltose. Therefore, malA
      encodes an alpha-1,4-glucosidase or maltase, which also liberates glucose from
      sucrose. Subcloning experiments indicated that malA does not possess its own
      promoter and is cotranscribed with malR. Its expression could not be stimulated
      when maltose was added to the growth medium. Chromosomal inactivation of malR led
      to reduced maltose utilization, although alpha-glucosidase activity in the malR
      mutant was slightly higher than in the wild type. In the mutant strain, maltose
      uptake was reduced and inducibility of the transport activity was partially lost.
      It seems that MalR participates in the regulation of the gene(s) for maltose
      transport and is needed for their full expression. Thus, the malRA genes
      constitute an essential genetic locus for maltosaccharide utilization in S.
      xylosus

PMID- 7730273
TI  - The NarX and NarQ sensor-transmitter proteins of Escherichia coli each require
      two conserved histidines for nitrate-dependent signal transduction to NarL.
AB  - The NarX, NarQ, and NarL proteins of Escherichia coli constitute a two-component
      regulatory system that controls the expression of a number of anaerobic
      respiratory pathway genes in response to nitrate. NarX and NarQ are sensor
      transmitter proteins that can independently detect the presence of nitrate in the
      cell environment and transmit this signal to the response regulator, NarL. Upon
      activation, NarL binds DNA and modulates the expression of its target genes by
      the repression or activation of transcription. NarX and NarQ each contain a
      conserved histidine residue that corresponds to the site of autophosphorylation
      of other sensor-transmitter proteins. They also contain a second conserved
      histidine residue that is present in the NarX, NarQ, UhpB, DegS, and ComP
      subfamily of sensor-transmitter proteins. The second histidine is located near a
      universally conserved asparagine residue, the role of which in signal
      transduction is unknown. To investigate the role of these conserved amino acids
      in the NarX and NarQ proteins, we mutated the narX and narQ genes by site
      directed mutagenesis. In vivo, each mutation severely impaired NarL-dependent
      activation or repression of reporter gene expression in response to nitrate. The
      in vivo data suggest that the environmental signal nitrate controls both the
      kinase and phosphatase activities of the two sensor-transmitter proteins. The
      altered NarX and NarQ proteins were purified and shown to be defective in their
      ability to autophosphorylate in the presence of [gamma-32P]ATP. The NarX and NarQ
      proteins with amino acid substitutions at the first conserved histidine position
      were also unable to dephosphorylate NarL-phosphate in vitro. In contrast, the
      proteins containing amino acid substitutions at the second conserved histidine or
      at the conserved asparagine residue retained NarL-phosphate dephosphorylation
      activity. The conserved histidine and asparagine residues are essential for NarX
      and NarQ function, and this suggests that other two-component sensor-transmitter
      proteins may function in a similar fashion.

PMID- 7730274
TI  - Analysis of a 24-kilodalton protein associated with the polyhydroxyalkanoic acid
      granules in Alcaligenes eutrophus.
AB  - A 5.0-kbp genomic EcoRI restriction fragment which complemented a third subclass
      of polyhydroxyalkanoic acid (PHA)-leaky mutants of A. eutrophus that accumulated
      PHA at a lower rate than the wild type was cloned from Alcaligenes eutrophus H16.
      A 687-bp phaPAe gene on this fragment encoded a 24-kDa protein (M(r) = 23,963),
      which was referred to as the GA24 protein. The GA24 protein was solubilized from
      the granules and purified to electrophoretic homogeneity, and antibodies against
      the GA24 protein were obtained. The GA24 protein bound to the surface of PHA
      granules, as revealed by immunoelectron microscopy of whole cells and of
      artificial PHA granules. The GA24 protein contributed approximately 5% (wt/wt) of
      the total cellular protein, and it was the predominant protein present in the
      granules. It was synthesized only in cells accumulating PHA and only in amounts
      that could be bound to the granules; no soluble GA24 protein was detected.
      Tn5::mob-induced phaPAe mutants which were unable to synthesize intact GA24
      protein formed only one large PHA granule per cell. The amino acid sequence of
      the GA24 protein revealed two closely related stretches consisting exclusively of
      nonhydrophilic amino acids at the C-terminal region, which are presumably
      involved in the binding of GA24 to the granules, as was recently proposed for a
      similar protein in Rhodococcus ruber. The GA24 protein seems to be a
      representative of phasins, which are a new class of protein that form a layer at
      the surface of PHA granules, like oleosins, which form a layer at the surface of
      triacylglycerol inclusions in oilseed plants.

PMID- 7730275
TI  - Purification and structural characterization of a flavoprotein induced by iron
      limitation in Methanobacterium thermoautotrophicum Marburg.
AB  - Cells of Methanobacterium thermoautotrophicum (strain Marburg) grown under iron
      limiting conditions were found to synthesize a soluble polypeptide as one of the
      major cell proteins. This polypeptide purified as a homotetramer (170 kDa
      [subunit molecular mass, 43 kDa]) had a UV-visible spectrum typical of
      flavoproteins and contained 0.7 mol of flavin mononucleotide per mol of monomer.
      Quantitative analysis by immunoblotting with polyclonal antibodies indicated that
      the flavoprotein, which amounts to about 0.6% of soluble cell protein under iron
      sufficient conditions (> or = 50 microM Fe2+), was induced fivefold by iron
      limitation (< 12 microM Fe2+). The flavoprotein-encoding gene, fprA, was cloned
      and sequenced. Sequence analysis revealed a well-conserved archaebacterial
      consensus promoter upstream of fprA, a flavodoxin signature within fprA, and 28%
      amino acid identity with a putative flavin mononucleotide-containing protein of
      Rhodobacter capsulatus which is found within an operon involved in nitrogen
      fixation. A possible physiological function for the flavoprotein is discussed.

PMID- 7730276
TI  - Three distinct quinoprotein alcohol dehydrogenases are expressed when Pseudomonas
      putida is grown on different alcohols.
AB  - A bacterial strain that can utilize several kinds of alcohols as its sole carbon
      and energy sources was isolated from soil and tentatively identified as
      Pseudomonas putida HK5. Three distinct dye-linked alcohol dehydrogenases (ADHs),
      each of which contained the prosthetic group pyrroloquinoline quinone (PQQ), were
      formed in the soluble fractions of this strain grown on different alcohols. ADH I
      was formed most abundantly in the cells grown on ethanol and was similar to the
      quinoprotein ADH reported for P. putida (H. Gorisch and M. Rupp, Antonie
      Leeuwenhoek 56:35-45, 1989) except for its isoelectric point. The other two ADHs,
      ADH IIB and ADH IIG, were formed separately in the cells grown on 1-butanol and
      1,2-propanediol, respectively. Both of these enzymes contained heme c in addition
      to PQQ and functioned as quinohemoprotein dehydrogenases. Potassium ferricyanide
      was an available electron acceptor for ADHs IIB and IIG but not for ADH I. The
      molecular weights were estimated to be 69,000 for ADH IIB and 72,000 for ADH IIG,
      and both enzymes were shown to be monomers. Antibodies raised against each of the
      purified ADHs could distinguish the ADHs from one another. Immunoblot analysis
      showed that ADH I was detected in cells grown on each alcohol tested, but ethanol
      was the most effective inducer. ADH IIB was formed in the cells grown on alcohols
      of medium chain length and also on 1,3-butanediol. Induction of ADH IIG was
      restricted to 1,2-propanediol or glycerol, of which the former alcohol was more
      effective. These results from immunoblot analysis correlated well with the
      substrate specificities of the respective enzymes. Thus, three distinct
      quinoprotein ADHs were shown to be synthesized by a single bacterium under
      different growth conditions.

PMID- 7730277
TI  - OlpB, a new outer layer protein of Clostridium thermocellum, and binding of its S
      layer-like domains to components of the cell envelope.
AB  - Several proteins of Clostridium thermocellum possess a C-terminal triplicated
      sequence related to bacterial cell surface proteins. This sequence was named the
      SLH domain (for S-layer homology), and it was proposed that it might serve to
      anchor proteins to the cell surface (A. Lupas, H. Engelhardt, J. Peters, U.
      Santarius, S. Volker, and W. Baumeister, J. Bacteriol. 176:1224-1233, 1994). This
      hypothesis was investigated by using the SLH-containing protein ORF1p from C.
      thermocellum as a model. Subcellular fractionation, immunoblotting, and electron
      microscopy of immunocytochemically labeled cells indicated that ORF1p was located
      on the surface of C. thermocellum. To detect C. thermocellum components
      interacting with the SLH domains of ORF1p, a probe was constructed by grafting
      these domains on the C terminus of the MalE protein of Escherichia coli. The SLH
      domains conferred on the chimeric protein (MalE-ORF1p-C) the ability to bind
      noncovalently to the peptidoglycan of C. thermocellum. In addition, 125I-labeled
      MalE-ORF1p-C was shown to bind to SLH-bearing proteins transferred onto
      nitrocellulose, and to a 26- to 28-kDa component of the cell envelope. These
      results agree with the hypothesis that SLH domains contribute to the binding of
      exocellular proteins to the cell surface of bacteria. The gene carrying ORF1 and
      its product, ORF1p, are renamed olpB and OlpB (for outer layer protein B),
      respectively.

PMID- 7730278
TI  - Organization and growth phase-dependent transcription of methane genes in two
      regions of the Methanobacterium thermoautotrophicum genome.
AB  - Two regions of the Methanobacterium thermoautotrophicum genome containing genes
      that encode enzymes involved in methanogenesis (methane genes) have been cloned
      and sequenced to determine the extent of methane gene clustering and
      conservation. One region from the M. thermoautotrophicum strains delta H and
      Winter, extending approximately 13.5 kb upstream from the adjacent mvhDGAB and
      mrtBDGA operons that encode the methyl-viologen-reducing hydrogenase (MVH) and
      the methyl coenzyme M reductase II (MRII), respectively, was sequenced, and 76%
      sequence identity and very similar gene organizations were demonstrated. Five
      closely linked open reading frames were located immediately upstream of the mvh
      operon and were designated flpECBDA. The flpCBD genes encode amino acid sequences
      that are 31, 47, and 65% identical to the primary sequences of the alpha and beta
      subunits of formate dehydrogenase and the delta subunit of MVH, respectively.
      Located immediately upstream of the flp genes was the mth gene, which encodes the
      H2-dependent methylene-tetrahydromethanopterin dehydrogenase (MTH). In contrast
      to this mth-flp-mvh-mrt cluster of methane genes, a separate approximately 5.4-kb
      genomic fragment cloned from M. thermoautotrophicum delta H contained only one
      methane gene, the mtd gene, which encodes the 8-hydroxy-5-deazaflavin (H2F420)
      dependent methylene-tetrahydromethanopterin dehydrogenase (MTD). Northern (RNA)
      blot experiments demonstrated that mth was transcribed only at early growth
      stages in fermentor-grown cultures of M. thermoautotrophicum delta H, whereas mtd
      was transcribed at later growth stages and in the stationary phase. Very similar
      transcription patterns have been observed by T.D. Pihl, S. Sharma, and J. N.
      Reeve (J. Bacteriol. 176:6384-6391, 1994) for the MRI- and MRII-encoding operons,
      mrtBDGA and mcrBDCGA, im M. thermoautotrophicum deltaH, suggesting coordinated
      regulation of methane gene expression. In contrast to the growth phase-dependent
      transcription of the mth/mrt and mtd/mcr genes, transcription of the mvhDGAB and
      frhADGB operons, which encode the two (NiFe) hydrogenases in M.
      thermoautotrophicum deltaH, was found to occur at all growth stages.

PMID- 7730279
TI  - Regulation of nucleoside diphosphate kinase and secretable virulence factors in
      Pseudomonas aeruginosa: roles of algR2 and algH.
AB  - Alginate is an important virulence factor for Pseudomonas aeruginosa during
      infection of the lungs of cystic fibrosis patients. The genes encoding enzymes
      for alginate production by P. aeruginosa are normally silent. They are activated
      in response to several environmental conditions, including high osmolarity,
      exposure to ethanol, or long-term growth under conditions of nutrient
      deprivation. Several genes which participate in the activation of alginate gene
      promoters have been identified; among these is the algR2 (algQ) gene. AlgR2 is an
      18-kDa protein which has been shown to regulate the critical algD gene encoding
      GDP-mannose dehydrogenase as well as to regulate the levels of a tricarboxylic
      acid cycle enzyme, i.e., succinyl coenzyme A synthetase, and nucleoside
      diphosphate kinase (Ndk), an enzyme involved in nucleoside triphosphate
      synthesis. Succinyl coenzyme A synthetase and Ndk form a complex in P.
      aeruginosa. While algR2 is required for alginate synthesis at 37 degrees C, an
      algR2 insertion mutant was still able to make alginate slowly at 37 or at 30
      degrees C. We used this observation to identify and clone a gene, termed algH. A
      strain with mutations in both algR2 and algH is unable to produce alginate at
      either 37 or 30 degrees C, and it is fully defective in Ndk production.

PMID- 7730280
TI  - Variable expression of class 1 outer membrane protein in Neisseria meningitidis
      is caused by variation in the spacing between the -10 and -35 regions of the
      promoter.
AB  - The class 1 outer membrane protein encoded by the porA gene of Neisseria
      meningitidis is a candidate for a vaccine against meningococcal infection. The
      expression of class 1 outer membrane protein displays phase variation between
      three expression levels. Northern (RNA) blot and primer extension analysis
      revealed that this phase variation is regulated at the transcriptional level. The
      start site for transcription is located 59 bp upstream of the translational
      initiation codon. Sequence analysis of the promoter region of the porA gene of a
      variant without class 1 protein expression revealed nine contiguous guanidine
      residues between the -10 and -35 domains. Comparison of promoter sequences of
      different phase variants indicated that the length of the polyguanidine stretch
      correlated with the expression level of the class 1 outer membrane protein; the
      presence of 11, 10, or 9 contiguous guanidine residues results in high levels,
      medium levels, or no expression of class 1 mRNA, respectively. These results
      suggest that the variable porA expression levels seen in different isolates are
      modulated by guanidine residue insertion and/or deletion due to slipped-strand
      mispairing on the polyguanidine stretch within the intervening sequence of the 
      35 and -10 regions of the promoter. The phase variation of class 1 outer membrane
      protein may provide a molecular mechanism to evade the host immune defense.
      Therefore, the protective efficacy of a vaccine based on class 1 outer membrane
      protein may be questioned.

PMID- 7730281
TI  - Purification and characterization of the major surface array protein from the
      avirulent Bacillus anthracis Delta Sterne-1.
AB  - Many prokaryotic organisms possess surface layer (S-layer) proteins that are
      components of the outermost cell envelope. With immunogold labeling, it was
      demonstrated that the protein extractable antigen 1 (EA1) was localized on the
      outer surface and specifically to cell wall fragments from Bacillus anthracis
      which retained the S layer. When grown in rich medium under aerobic conditions,
      the avirulent strain Delta Sterne-1 released large amounts of EA1 into the
      medium. This EA1 had no higher-order structure initially but formed two
      dimensional crystals under defined conditions. The released EA1 was purified in
      aqueous buffers with a three-step procedure and found to have a mass of 95 kDa
      when subjected to denaturing sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). N-terminal sequence data revealed exact identity to
      the first eight residues of the S-layer protein from B. thuringiensis 4045. Gel
      permeation chromatography of the purified EA1 under nondenaturing conditions
      revealed a single peak corresponding to a mass of approximately 400 kDa,
      suggesting that a tetramer or dimer of dimers was the primary species in
      solution. SDS-PAGE of EA1 purified in the absence of protease inhibitors revealed
      specific proteolytic processing to an 80-kDa form, which immunoreacted with
      polyclonal anti-EA1 antibodies. This proteolytic cleavage of EA1 to 80 kDa was
      duplicated with purified EA1 and the protease trypsin or pronase.

PMID- 7730282
TI  - Active contribution of two domains to cooperative DNA binding of the enhancer
      binding protein nitrogen regulator I (NtrC) of Escherichia coli: stimulation by
      phosphorylation and the binding of ATP.
AB  - Activation by the prokaryotic activator nitrogen regulator I (NRI, or NtrC) of
      Escherichia coli requires an interaction between two NRI dimers. ATP-dependent
      phosphorylation stimulates this tetramerization, which can be detected as
      cooperative binding to DNA. A polypeptide containing only the DNA-binding
      carboxyl-terminal domain has been previously shown to bind noncooperatively to
      DNA. Our primary purpose was to determine whether the highly conserved N-terminal
      domain or the ATP-binding central domain is required for cooperative DNA binding.
      Because ATP was present in the experiments that showed that phosphorylation
      enhances cooperative bindings, it is possible that ATP and not phosphorylation
      stimulated cooperative binding. Our secondary purpose was to separately assess
      the effects of ATP and phosphorylation on cooperative binding. We showed that a
      variant with a deletion of the central domain, NRI-(delta 143-398), binds
      cooperatively as well as unphosphorylated wild-type NRI, implying that the N
      terminal domain mediates phosphorylation-independent cooperative binding.
      Phosphorylation of NRI-(delta 143-398) did not further stimulate this binding,
      suggesting that the ATP-binding central domain may be required for the
      phosphorylation-dependent enhancement. Cooperative binding was enhanced by either
      acetyl-phosphate-dependent (i.e., ATP-independent) phosphorylation of NRI or the
      specific binding of ATP to the central domain. Their effects were not additive, a
      finding which is consistent with the interpretation that each promotes a similar
      dimer-dimer interaction. We discuss these results within the context of the
      hypothesis that the highly conserved N-terminal domain mediates phosphorylation
      independent cooperativity and the central domain is required for cooperativity
      stimulated by ATP binding or phosphorylation.

PMID- 7730283
TI  - Interaction of the Neisseria gonorrhoeae PilA protein with the pilE promoter
      involves multiple sites on the DNA.
AB  - PilA is the putative DNA-binding component of a two-component system that
      regulates transcription of the pilin expression locus (pilE) of Neisseria
      gonorrhoeae. Here we report the purification of the PilA protein and
      characterization of its DNA-binding activity. PilA was overproduced in
      Escherichia coli with an isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible
      expression vector. Cell extracts were prepared by sonication and fractionated by
      anion-exchange chromotography, followed by dye affinity chromatography with
      Cibacron Blue. Proteins were eluted by using a gradient of KCl, and PilA
      containing fractions were identified by immunoblot analysis with a polyclonal
      anti-PilA antiserum. Purified PilA was judged to be > 90% pure, as determined by
      Coomassie blue staining and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. PilA purified in this manner was used to develop a gel
      retardation assay with a 301-bp fragment containing the pilE promoter (PpilE) and
      upstream sequences as a probe. A fragment of similar size containing the E. coli
      aroH promoter was used as a negative control. Competition experiments using a 100
      to 1,000-fold excess of unlabelled DNA fragments confirmed the specificity of
      PilA binding to the pilE promoter. To localize the PilA binding site within the
      301-bp PpilE fragment, stepwise deletions were generated by PCR and the fragments
      were examined in the gel shift assay. The results of these experiments show that
      there are two regions upstream of PpilE that are required for binding by PilA.
      Taken together, these data indicate that while PilA binds specifically to the
      upstream region of the pilE gene, this interaction is complex and likely involves
      multiple regions of this DNA sequence.

PMID- 7730284
TI  - Purification from Fusobacterium mortiferum ATCC 25557 of a 6-phosphoryl-O-alpha-D
      glucopyranosyl:6-phosphoglucohydrolase that hydrolyzes maltose 6-phosphate and
      related phospho-alpha-D-glucosides.
AB  - 6-Phosphoryl-O-alpha-D-glucopyranosyl:6-phosphoglucohydrolase (6-phospho-alpha
      glucosidase) has been purified from Fusobacterium mortiferum ATCC 25557. p
      Nitrophenyl-alpha-D-glucopyranoside 6-phosphate (pNP alpha Glc6P) served as the
      chromogenic substrate for detection and assay of enzyme activity. The O2
      sensitive, metal-dependent phospho-alpha-glucosidase was stabilized during
      purification by inclusion of dithiothreitol and Mn2+ ion in chromatography
      buffers. Various 6-phosphoryl-O-alpha-linked glucosides, including maltose 6
      phosphate, pNP alpha Glc6P, trehalose 6-phosphate, and sucrose 6-phosphate, were
      hydrolyzed by the enzyme to yield D-glucose 6-phosphate and aglycone moieties in
      a 1:1 molar ratio. 6-Phospho-alpha-glucosidase (M(r) of approximately 49,000; pI
      of approximately 4.9) is activated by Fe2+, Mn2+, Co2+, and Ni2+, and the maximum
      rate of pNP alpha Glc6P hydrolysis occurs at 40 degrees C within the pH range 7.0
      to 7.5. The sequence of the first 32 amino acids of 6-phospho-alpha-glucosidase
      exhibits 67% identity (90% similarity) to that deduced for the N terminus of a
      putative phospho-beta-glucosidase (designated ORF f212) encoded by glvG in
      Escherichia coli. Western blots involving highly specific polyclonal antibody
      against 6-phospho-alpha-glucosidase and spectrophotometric analyses with pNP
      alpha Glc6P revealed only low levels of the enzyme in glucose-, mannose-, or
      fructose-grown cells of F. mortiferum. Synthesis of 6-phospho-alpha-glucosidase
      increased dramatically during growth of the organism on alpha-glucosides, such as
      maltose, alpha-methylglucoside, trehalose, turanose, and palatinose.

PMID- 7730285
TI  - Identification of the region of a 14-kilodalton protein of Rhodococcus ruber that
      is responsible for the binding of this phasin to polyhydroxyalkanoic acid
      granules.
AB  - The function of the polyhydroxyalkanoic acid (PHA) granule-associated GA14
      protein of Rhodococcus ruber was investigated in Escherichia coli XL1-Blue, which
      coexpressed this protein with the polyhydroxybutyric acid (PHB) biosynthesis
      operon of Alcaligenes eutrophus. The GA14 protein had no influence on the
      biosynthesis rate of PHB in E. coli XL1-Blue(pSKCO7), but this recombinant E.
      coli strain formed smaller PHB granules than were formed by an E. coli strain
      that expressed only the PHB operon. Immunoelectron microscopy with GA14-specific
      antibodies demonstrated the binding of GA14 protein to these mini granules. In a
      previous study, two hydrophobic domains close to the C terminus of the GA14
      protein were analyzed, and a working hypothesis that suggested an anchoring of
      the GA14 protein in the phospholipid monolayer surrounding the PHA granule core
      by these hydrophobic domains was developed (U. Pieper-Furst, M. H. Madkour, F.
      Mayer, and A. Steinbuchel, J. Bacteriol. 176:4328-4337, 1994). This hypothesis
      was confirmed by the construction of C-terminally truncated variants of the GA14
      protein lacking the second or both hydrophobic domains and by the demonstration
      of their inability to bind to PHB granules. Further confirmation of the
      hypothesis was obtained by the construction of a fusion protein composed of the
      acetaldehyde dehydrogenase II of A. eutrophus and the C terminus of the GA14
      protein containing both hydrophobic domains and by its affinity to native and
      artificial PHB granules.

PMID- 7730286
TI  - Nucleoside diphosphate kinase from Escherichia coli.
AB  - Nucleoside diphosphate (NDP) kinase from Escherichia coli was purified to
      homogeneity and was crystallized. Gel filtration analysis of the purified enzyme
      indicated that it forms a tetramer. The enzyme was phosphorylated with [gamma
      32P]ATP, and the pH stability profile of the phosphoenzyme indicated that two
      different amino acid residues were phosphorylated. Both a histidine residue and
      serine residues, including Ser-119 and Ser-121, appear to be phosphorylated. A
      Ser119Ala/Ser121Ala double mutant (i.e., with a Ser-to-Ala double mutation at
      positions 119 and 121), as well as Ser119Ala and Ser121Ala mutants, was isolated.
      All of these retained NDP kinase activity; also, both the Ser119Ala and Ser121Ala
      mutants could still be autophosphorylated. In the case of the double mutant, a
      slight autophosphorylation activity, which was resistant to acid treatment, was
      still detected, indicating that an additional minor autophosphorylation site
      besides His-117 exists. These results are discussed in light of the recent report
      of N. J. MacDonald et al. on the autophosphorylation of human NDP kinase (J.
      Biol. Chem. 268:25780-25789, 1993).

PMID- 7730287
TI  - Differential effects of deletions in lcrV on secretion of V antigen, regulation
      of the low-Ca2+ response, and virulence of Yersinia pestis.
AB  - The Yersinia pestis V antigen is necessary for full induction of low-calcium
      response (LCR) stimulon virulence gene transcription, and it also is a secreted
      protein believed to have a direct antihost function. We made four nonpolar
      deletions in lcrV of Y. pestis to determine if secretion, regulation, and
      virulence functions could be localized within the V antigen (LcrV). Deletion of
      amino acids 25 to 40 caused secretion of LcrV to be decreased in efficiency;
      however, removal of residues 108 to 125 essentially abolished LcrV secretion.
      Neither mutation had a significant effect on LCR regulation. This showed that
      LcrV does not have to be secreted to have its regulatory effect and that the
      internal structure of V antigen is necessary for its secretion. Both mutants were
      avirulent in mice, showing that the regulatory effect of LcrV could be separated
      genetically from its virulence role and raising the possibility that residues 25
      to 40 are essential for the virulence function. This study provides the best
      genetic evidence available that LcrV per se is necessary for the virulence of Y.
      pestis. The repressed LCR phenotype of a mutant lacking amino acids 188 to 207 of
      LcrV raised the possibility that the deleted region is necessary for regulation
      of LCR induction; however, this mutant LcrV was weakly expressed and may not have
      been present in sufficient amounts to have its regulatory effect. In double
      mutants containing this mutant lcrV and also lacking expression of known LCR
      negative regulators (LcrG, LcrE, and LcrH), full induction of the LCR occurred in
      the absence of functional LcrV, indicating that LcrV promotes induction not as an
      activator per se but rather by inhibiting negative regulators.

PMID- 7730288
TI  - Comparative analyses reveal a highly conserved endoglucanase in the cellulolytic
      genus Fibrobacter.
AB  - An RNA probe complementary to the endoglucanase 3 gene (cel-3) of Fibrobacter
      succinogenes S85 hybridized to chromosomal DNAs from isolates representing the
      genetic diversity of the genus. The probe was subsequently used to identify
      putative cel-3-containing clones from genomic libraries of representative
      Fibrobacter isolates. Comparative sequence analyses of the cloned cel-3 genes
      confirmed that cel-3 is conserved among Fibrobacter isolates and that the
      ancestral cel-3 gene appears to have coevolved with the genus, since the same
      genealogy was inferred from sequence comparisons of 16S rRNAs and cel-3 genes.
      Hybridization comparisons using a xylanase gene probe suggested similar
      conservation of this gene. Together the data indicate that the cellulolytic
      apparatus is conserved among Fibrobacter isolates and that comparative analyses
      of homologous elements of the apparatus from different members, in relationship
      to the now established phylogeny of the genus, could serve to better define the
      enzymatic basis of fiber digestion in this genus.

PMID- 7730289
TI  - Characterization of a zwf mutant of Synechococcus sp. strain PCC 7942.
AB  - A mutant of the cyanobacterium Synechococcus sp. strain PCC 7942 carrying a
      disrupted gene encoding glucose-6-phosphate dehydrogenase (zwf) produced no
      detectable glucose-6-phosphate dehydrogenase as assessed by enzyme assay and
      Western blot (immunoblot) analysis. This mutant exhibited significantly impaired
      dark viability.

PMID- 7730290
TI  - Sequence and distribution of IS1312: evidence for horizontal DNA transfer from
      Rhizobium meliloti to Agrobacterium tumefaciens.
AB  - Two novel insertion sequences, IS1312 and IS1313, were found in pTiBo542, the Ti
      plasmid of Agrobacterium tumefaciens strains Bo542 and A281. Nucleotide
      sequencing and Southern hybridization revealed that IS1312 and IS1313 are
      homologous to Rhizobium meliloti ISRm1 and ISRm2, respectively. IS1312, ISRm1,
      and another Agrobacterium insertion sequence, IS426, belong to the same IS3
      family of insertion sequences; however, IS1312 is more closely related to the
      Rhizobium ISRm1 than it is to the Agrobacterium IS426. The distribution patterns
      of these insertion elements and their sequence similarities suggest that IS1312
      and IS1313 were horizontally transferred from R. meliloti to A. tumefaciens.

PMID- 7730291
TI  - FtsZ and nucleoid segregation during outgrowth of Bacillus subtilis spores.
AB  - Spores of a strain of Bacillus subtilis in which ftsZ was under the control of
      the spac promoter were allowed to germinate and grow out in the presence of
      increasing concentrations of isopropyl-beta-D-thiogalactopyranoside (IPTG). Over
      the IPTG concentration range of 0 to 10(-3) M, the level of FtsZ from the time
      when the first nucleoid segregations were occurring, measured in Western blot
      (immunoblot) transfer experiments, varied between 15 and 100% of that in the wild
      type. Septation was completely blocked (for at least several hours) when the
      amount of FtsZ was < 30% of the wild-type level. At all levels of ftsZ induction,
      the timing and rate of segregation of nucleoids following the first round of
      replication were unaltered. It is concluded that FtsZ has no direct role in
      nucleoid segregation in this situation.

PMID- 7730292
TI  - High-level expression of soluble recombinant RNase P protein from Escherichia
      coli.
AB  - We have expressed recombinant RNase P protein from Escherichia coli in high
      yield. A hexahistidine sequence at the amino terminus allowed protein
      purification in a single step. Mass spectrometry confirmed the molecular weight
      of the purified protein and indicated a purity of > 95%. Protein functionality
      was demonstrated by reconstitution of active holoenzyme.

PMID- 7730293
TI  - Glucosyl diglyceride lipid structures in Deinococcus radiodurans.
AB  - The structures of two lipids from the radiation-resistant bacterium Deinococcus
      radiodurans are reported here: 1,2-diacyl-3-alpha-glucopyranosyl-glycerol and 3-O
      [6'-O-(1",2"-diacyl- 3"-phosphoglycerol)-alpha-glucopyranosyl]-1,2
      diacylglycerol. These lipids are strikingly different from previously
      characterized polar lipids from this organism, in that they are not unique to the
      genus Deinococcus and indeed have counterparts in both gram-negative and gram
      positive bacteria. Moreover, as examples of glucose-containing lipids, they
      further illustrate the diversity of carbohydrate-containing lipids in D.
      radiodurans, from which lipids containing galactose and N-acetylglucosamine have
      already been structurally characterized.

PMID- 7730294
TI  - Cloning and characterization of the Bacillus subtilis birA gene encoding a
      repressor of the biotin operon.
AB  - The Bacillus subtilis birA gene, which regulates biotin biosynthesis, has been
      cloned and characterized. The birA gene maps at 202 degrees on the B. subtilis
      chromosome and encodes a 36,200-Da protein that is 27% identical to Escherichia
      coli BirA protein. Three independent mutations in birA that lead to deregulation
      of biotin synthesis alter single amino acids in the amino-terminal end of the
      protein. The amino-terminal region that is affected by these three birA mutations
      shows sequence similarity to the helix-turn-helix DNA binding motif previously
      identified in E. coli BirA protein. B. subtilis BirA protein also possesses
      biotin-protein ligase activity, as judged by its ability to complement a
      conditional lethal birA mutant of E. coli.

PMID- 7730295
TI  - Sulredoxin: a novel iron-sulfur protein of the thermoacidophilic archaeon
      Sulfolobus sp. strain 7 with a Rieske-type [2Fe-2S] center.
AB  - A novel pink [2Fe-2S] protein has been purified from the cytosol fraction of the
      thermoacidophilic archaeon Sulfolobus sp. strain 7 (originally named Sulfolobus
      acidocaldarius 7) and called "sulredoxin." Its absorption, circular dichroism,
      and electron paramagnetic resonance spectra suggest the presence of a Rieske-type
      [2Fe-2S] cluster (g-factors of 2.01, 1.91, and 1.79; average g-factor [gav] =
      1.90) which is remarkably similar to that of Thermus thermophilus respiratory
      Rieske FeS protein (J. A. Fee, K. L. Findling, T. Yoshida, R. Hille, G. E. Tarr,
      D. O. Hearshen, W. R. Dunham, E. P. Day, T. A. Kent, and E. Munck, J. Biol. Chem.
      259:124-133, 1984) and distinctively different from those of the plant-type
      ferredoxins (gav = 1.96). Sulredoxin, which is the first Rieske-type [2Fe-2S]
      protein isolated from an archaeal species, does not function as an electron
      acceptor of the cognate 2-oxoacid:ferredoxin oxidoreductase. Whether sulredoxin
      is derived from the archaeal membrane-bound respiratory Rieske-type FeS center
      (gy = 1.91) is the subject of further investigation.

PMID- 7730296
TI  - Genetic transfer by conjugation in the thermophilic green sulfur bacterium
      Chlorobium tepidum.
AB  - The broad-host-range IncQ group plasmids pDSK519 and pGSS33 were transferred by
      conjugation from Escherichia coli into the thermophilic green sulfur bacterium
      Chlorobium tepidum. C. tepidum exconjugants expressed the kanamycin and
      ampicillin-chloramphenicol resistances encoded by pDSK519 and pGSS33,
      respectively. Ampicillin resistance was a particularly good marker for selection
      in C. tepidum. Both pDSK519 and pGSS33 were stably maintained in C. tepidum at
      temperatures below 42 degrees C and could be transferred between C. tepidum and
      E. coli without modifications. Conjugation frequencies ranged from 10(-1) to 10(
      4) exconjugants per donor cell, and frequencies of 10(-2) to 10(-3) were
      consistently obtained when ampicillin resistance was used as a selectable marker.
      Methods for growth of C. tepidum on agar, isolation of plating strains and
      antibiotic-resistant mutants of wild-type C. tepidum cells, and optimum
      conditions for conjugation were also investigated.

PMID- 7730297
TI  - Structural and functional analyses of the transcription-translation proteins NusB
      and NusE.
AB  - The NusB and NusE (ribosomal protein S10) proteins function in transcription and
      translation. The two proteins form a complex that binds to the boxA sequence
      found in the leader RNA of rrn operons; boxA is required for transcription
      antitermination in rrn operons. Although binding of these two proteins to the
      boxA RNA of the bacteriophage lambda nut site has not been observed, both NusB
      and NusE as well as the RNA boxA sequence are required for lambda N-mediated
      antitermination. Studies identifying the amino acid changes caused by mutations
      in nusB and nusE and relating these changes to altered function are reported. It
      is concluded that boxA is essential for an effective NusB contribution to N
      mediated antitermination and that by mutation NusB may be changed to allow more
      effective binding to boxA variants.

PMID- 7730298
TI  - icdB mutants of Escherichia coli.
AB  - icdB mutations map at 16 min, lead to the specific loss of citrate synthase, and
      are complemented by a prophage containing a gltA+ gene. Thus, they are allelic
      with gltA.

PMID- 7730299
TI  - Chlamydia trachomatis RNA polymerase alpha subunit: sequence and structural
      analysis.
AB  - We describe the cloning and sequence analysis of the region surrounding the gene
      for the alpha subunit of RNA polymerase from Chlamydia trachomatis. This region
      contains genes for proteins in the order SecY, S13, S11, alpha, and L17, which
      are equivalent to Escherichia coli and Bacillus subtilis r proteins. The
      incorporation of chlamydial alpha subunit protein into the E. coli RNA polymerase
      holoenzyme rather than its truncated variant lacking the amino terminus suggests
      the existence of structural conservation among alpha subunits from distantly
      related genera.

PMID- 7730300
TI  - Identification of active site residues by site-directed mutagenesis of delta 5-3
      ketosteroid isomerase from Pseudomonas putida biotype B.
AB  - In order to assess the roles of specific amino acid residues in the delta 5-3
      ketosteroid isomerase from Pseudomonas putida biotype B during catalysis, we
      replaced aspartic acid 40 with asparagine (D40N) and tyrosine 16 with
      phenylalanine (Y16F) in the enzyme by site-directed mutagenesis. Both purified
      mutant enzymes resulted in profound decreases in catalytic activities, 10(3.3)
      fold in the Y16F mutant and 10(6.2)-fold in the D40N mutant. Aspartic acid 40 and
      tyrosine 16 of the enzyme are the corresponding amino acids in the active site of
      the homologous enzyme from Comamonas testosteroni. Our results indicate that
      active-site residues of the two homologous enzymes are similar. This is opposite
      to the previous identification of a cysteine in an active site-directed
      photoinactivation study of the enzyme.

PMID- 7730301
TI  - Switching nucleotide specificity of Ha-Ras p21 by a single amino acid
      substitution at aspartate 119.
AB  - We examined c-Ha-Ras harboring an aspartate to asparagine substitution at
      position 119 (mutation D119N). The Asp-119 is part of the conserved NKXD motif
      shared by members of the regulatory GTPase family. This asparagine residue has
      been proposed to participate in direct bonding to the guanine ring and to
      determine the guanine-nucleotide binding specificity. The D119N mutation was
      found to alter nucleotide specificity of Ha-Ras from guanine to xanthine, an
      observation that directly supports the essential role of hydrogen bonding between
      the side chain of the aspartic acid residue and the guanine ring in nucleotide
      binding specificity. Besides nucleotide binding specificity, the D119N mutation
      has little or no effect on the interaction of Ha-Ras with SDC25C, SOS1, GAP, or
      Raf. Neither does it affect the hydrolysis of nucleotide triphosphate. Like
      xanthine-nucleotide-specific EF-Tu, xanthine-nucleotide-specific Ras and related
      proteins will be useful tools for elucidating cellular systems containing
      multiple regulatory GTPases.

PMID- 7730302
TI  - Oleate and other long chain fatty acids stimulate low density lipoprotein
      receptor activity by enhancing acyl coenzyme A:cholesterol acyltransferase
      activity and altering intracellular regulatory cholesterol pools in cultured
      cells.
AB  - Modification of dietary fatty acid composition results in changes in plasma
      cholesterol levels in man. We examined the effect of in vitro fatty acid
      supplementation on low density lipoprotein (LDL) receptor activity in cultured
      cells and questioned whether changes were related to fatty acid-induced
      alterations in acyl-CoA: cholesterol acyltransferase (ACAT) activity.
      Preincubation of cultured cells (i.e. human skin fibroblasts, J774 macrophages,
      and HepG2 cells) with oleic acid (oleic acid:bovine serum albumin molar ratio
      2:1) at 37 degrees C for longer than 2 h resulted in a 1.2- to 1.5-fold increase
      in LDL cell binding at 4 degrees C and LDL cell degradation at 37 degrees C.
      Scatchard analysis showed that oleic acid increased LDL receptor number but not
      LDL affinity (Kd). Fatty acid supplementation of J774 macrophages increased both
      LDL receptor activity and cholesteryl ester accumulation. The ACAT inhibitor, 58
      035, eliminated both effects, and increased ACAT activity preceded stimulation of
      LDL receptor activity by 1-2 h. Supplementation of macrophages with triolein
      emulsion particles also increased LDL cell binding and degradation, and addition
      of cholesterol to the emulsions abolished this effect. Among fatty acids tested,
      oleate (18:1), arachidonate (20:4), and eicosapentanoate (20:5) demonstrated the
      greatest effects. We hypothesize that certain fatty acids delivered to cells
      either in free form, or as triglyceride, first increase cellular ACAT activity,
      which then causes a decrease in an intracellular free cholesterol pool, signaling
      a need for increased LDL receptor activity. This mechanism may play a role in the
      effect of certain dietary fatty acids on LDL metabolism in vivo.

PMID- 7730303
TI  - Mechanism of protein modification by glyoxal and glycolaldehyde, reactive
      intermediates of the Maillard reaction.
AB  - The role of glyoxal and glycolaldehyde in protein cross-linking and N epsilon
      (carboxymethyl)lysine (CML) formation during Maillard reaction under
      physiological conditions was investigated. Incubation of bovine serum albumin
      with these reagents lead to rapid formation of C-2-imine cross-links and CML.
      Initial CML formation rate from glyoxal was not dependent on oxidation,
      suggesting an intramolecular Cannizzaro reaction. CML formation from
      glucose/lysine or Amadori product of both was strongly dependent on oxidation.
      Blocking of Amadori product by boric acid totally suppressed CML formation from
      Amadori product, but only by 37% in the glucose/lysine system. Trapping of
      glyoxal with aminoguanidine hardly suppressed CML formation from Amadori product,
      whereas it blocked 50% of CML production in the glucose/lysine system. While
      these results would support a significant role for glucose autoxidation in CML
      formation, the addition of lysine to a glucose/aminoguanidine incubation system
      catalyzed glyoxal-triazine formation 7-fold, thereby strongly suggesting that
      glucose autoxidation is not a factor for glyoxal-mediated CML formation. Based on
      these results, it can be estimated that approximately 50% of the CML forming in a
      glucose/lysine system originates from oxidation of Amadori product, and 40-50%
      originates from a pre-Amadori stage largely independent from glucose
      autoxidation. This step may be related to the so-called Namiki pathway of the
      Maillard reaction.

PMID- 7730304
TI  - Isotopomer analysis of citric acid cycle and gluconeogenesis in rat liver.
      Reversibility of isocitrate dehydrogenase and involvement of ATP-citrate lyase in
      gluconeogenesis.
AB  - We conducted an extensive mass isotopomer analysis of citric acid cycle and
      gluconeogenic metabolites isolated from livers of overnight fasted rats perfused
      with 4 mM glucose, 0.2 mM octanoate, 1 mM [U-13C3]lactate, and 0.2 mM [U
      13C3]pyruvate, in the anterograde or retrograde mode. In both perfusion modes,
      two distinct isotopomer patterns were observed: (i) those of phosphoenolpyruvate,
      glucose, malate, and aspartate and (ii) those of citrate, alpha-ketoglutarate,
      glutamate, and glutamine. Key citric acid cycle parameters and, hence, rates of
      gluconeogenesis, calculated (Lee, W.-N.P. (1989) J. Biol. Chem. 264, 13002-13004
      and Lee, W.-N.P. (1993) J. Biol. Chem. 268, 25522-25526) from our mass isotopomer
      data did not only vary, but lead to conclusions inconsistent with Lee's citric
      acid cycle model. Compared to lactate and pyruvate uptake, which sets an upper
      limit to glucose production, rates of gluconeogenesis calculated (i) with the
      phosphoenolpyruvate and citrate data were similar, but those calculated (ii) with
      the glutamate data amounted to only 60%, which is unlikely. All these conclusions
      are independent of the perfusion modes. We provide evidence that the following
      processes contribute to the observed labeling discrepancy: (i) the reversibility
      of the isocitrate dehydrogenase reaction and (ii) an active citrate cleavage
      pathway for the transfer of the oxaloacetate carbon skeleton from mitochondria to
      the cytosol. Also, a good fit of our labeling data was obtained with a model of
      citric acid cycle and gluconeogenesis which we developed to incorporate the above
      reactions (Fernandez, C.A., and Des Rosiers, C. (1995) J. Biol. Chem. 270, 10037
      10042). The following conclusions can be drawn from the calculated reaction
      rates: (i) about half of the lactate conversion to glucose occurs via the citrate
      cleavage pathway, (ii) the flux through the reversal of the isocitrate
      dehydrogenase reaction is almost as fast as that through the citrate synthase
      reaction, and (iii) the flux through citrate synthase and alpha-ketoglutarate
      dehydrogenase is 1.6- and 3.2-fold that through pyruvate carboxylase,
      respectively.

PMID- 7730305
TI  - Modeling of liver citric acid cycle and gluconeogenesis based on 13C mass
      isotopomer distribution analysis of intermediates.
AB  - We have developed and implemented a model that can predict the positional
      isotopomer distribution of various hepatic metabolites labeled with [U
      13C3]lactate and/or [U-13C3]pyruvate for given relative flux rates through the
      citric acid cycle and gluconeogenesis reactions. Our model includes (i) isotopic
      exchange between alpha-ketoglutarate and glutamate, (ii) a reversible isocitrate
      dehydrogenase reaction, (iii) an active ATP-citrate lyase, and (iv) aspartate and
      malate shuttles with separate cytosolic and mitochondrial pools for oxaloacetate,
      malate, and fumarate. A parameter estimation routine fit the mass isotopomer
      distribution of selected metabolites measured by gas chromatography-mass
      spectrometry to the model predicted distributions. We fit measured mass
      isotopomer distributions of phosphoenolpyruvate, citrate, alpha-ketoglutarate,
      glutamate, and pyruvate isolated from fasted rat livers perfused with [U
      13C3]lactate + [U-13C3]pyruvate. This fitting yielded rates which we express
      relative to that of pyruvate carboxylase: citric acid cycle represented by the
      irreversible alpha-ketoglutarate dehydrogenase = 0.32; citrate synthase = 0.64;
      reversal of isocitrate dehydrogenase = 0.52; citrate lyase = 0.33, aspartate
      shuttle = 0.24, and malate shuttle = 0.44. Rates calculated for the cytosolic and
      mitochondrial fumarate and malate dehydrogenase reactions are subject to
      uncertainties as indicated by identifiability analyses. Previous forms of our
      model that did not include pyruvate kinase, exchange of alpha-ketoglutarate with
      glutamate, reversibility of isocitrate dehydrogenase, and/or ATP-citrate lyase
      activity were not as successful at predicting our measured values. This model
      offers a general tool for studying the regulation of the citric acid cycle and
      gluconeogenesis and can be readily modified for any 13C-labeled lactate or
      pyruvate substrate.

PMID- 7730306
TI  - Interaction of autophosphorylated Ca2+/calmodulin-dependent protein kinase II
      with neuronal cytoskeletal proteins. Characterization of binding to a 190-kDa
      postsynaptic density protein.
AB  - Subcellular localization of Ca2+/calmodulin-dependent protein kinase II (CaMKII)
      by interaction with specific anchoring proteins may be an important mechanism
      contributing to the regulation of CaMKII. Proteins capable of binding CaMKII were
      identified by the use of a gel overlay assay with recombinant mouse CaMKII alpha
      (mCaMKII alpha) or Xenopus CaMKII beta (xCaMKII beta) 32P-autophosphorylated at
      Thr286/287 as a probe. Numerous [32P]CaMKII-binding proteins were identified in
      various whole rat tissue extracts, but binding was most prominent to forebrain
      proteins of 190 kDa (p190) and 140 kDa (p140). Fractionation of forebrain
      extracts localized p190 and p140 to a crude particulate/cytoskeletal fraction and
      isolated postsynaptic densities. [32P]m-CaMKII alpha-bound to p190 with an
      apparent Kd of 609 nM (subunit concentration) and a Bmax of 7.0 pmol of mCaMKII
      alpha subunit bound per mg of P2 protein, as measured using the overlay assay.
      Binding of 100 nM [32P]m-CaMKII alpha to p190 was competed by nonradioactive
      mCaMKII alpha autophosphorylated on Thr286 (EC50% = 200 nM), but to a much lesser
      extent by nonradioactive mCaMKII alpha autophosphorylated on Thr306 (EC50% > 2000
      nM). In addition, nonphosphorylated mCaMKII alpha was a poor competitor for
      [32P]mCaMKII alpha binding to p190. The competition data indicate that Ca2+/CaM
      dependent autophosphorylation at Thr286 promotes binding to p190, whereas,
      Ca2+/CaM-independent autophosphorylation at Thr306 does not enhance binding.
      Therefore, CaMKII may become localized to postsynaptic densities by p190
      following its activation by an increase of dendritic Ca2+ concentration.

PMID- 7730307
TI  - Complete inactivation of Escherichia coli uridine phosphorylase by modification
      of Asp5 with Woodward's reagent K.
AB  - Woodward's reagent K (WRK) completely inactivated Escherichia coli uridine
      phosphorylase by reversible binding in the active site (Ki = 0.07 mM) with
      subsequent modification of a carboxyl (k2 = 1.2 min-1). Neither substrate alone
      protected uridine phosphorylase from inactivation. The presence of phosphate did
      not affect the Ki and k2 values. The addition of uracil or uridine led to a
      significant increase of both Ki (to 2.5 or 2.1 mM, respectively) and k2 (to 6.1
      or 4.8 min-1, respectively) values. Thus, WRK could react in accordance with slow
      (high affinity) and fast (low affinity) mechanisms. Combined addition of
      phosphate and uracil completely protected uridine phosphorylase. Tryptic
      digestion yielded a single modified peptide (Ser4-Asp(WRK)-Val-Phe-His-Leu-Gly
      Leu-Thr-Lys13). Treatment of the modified enzyme with hydroxylamine led to
      removal of the bulky WRK residue and replacement of the Asp5 carboxyl by a
      hydroxamic group. The enzyme thus obtained recovered about 10% of initial
      specific activity, whereas its substrate binding ability changed only moderately;
      the Km values for phosphate and uridine were changed from 5.1 and 0.19 mM (or 7.3
      and 0.14 mM according to Leer et al. (Leer, J.C., Hammer-Jespersen, K., and M.
      Schwartz (1977) Eur. J. Biochem. 75, 217-224)) to 22.6 and 0.12 mM, respectively.
      The hydroxamic enzyme had higher thermostability than the native enzyme. The
      results obtained demonstrated the importance of the carboxyl at position 5. The
      loss of activity after selective group replacement is due to impaired
      stabilization of the transition state rather than to a decline in substrate
      affinity or change of the active site structure.

PMID- 7730308
TI  - Endopeptidase 24.16B. A new variant of endopeptidase 24.16.
AB  - A peptidase, isolated from rat testes, is inhibited by 1 mM o-phenanthroline, 1
      microM N-(1-(R,S)-carboxyl-3-phenylpropyl)-Ala-Ala-Phe-p-aminobenzoate, and 6 mM
      Pro-Ile, properties similar to those ascribed to endopeptidase 24.16. The enzyme
      hydrolyzes dynorphin A-8, neurotensin 1-13, angiotensin I, and substance P.
      Kinetic analysis of a series of angiotensin I analogs showed that substitutions
      at P-1, P-1', or P-2' had little effect on Km or Kcat. Variation of peptide size
      with a series of dynorphin A peptides showed chain length to be significant. The
      peptidase cleaved dynorphin A-8 at both Leu5-Arg6 and Arg6-Arg7, and neurotensin
      1-13 at Pro10-Tyr11 and Arg8-Arg9. In contrast, rat endopeptidase 24.16 cleaves
      dynorphin A-8 at Gly4-Leu5 and Leu5-Arg6, and neurotensin 1-13 only at Pro10
      Tyr11. These findings, as well as the observation that endopeptidase 24.16
      exhibits a considerably higher affinity for Pro-Ile, Ki = 90 microM, indicates
      the peptidase isolated in this study is related to, but distinct from, rat
      endopeptidase 24.16. We propose that this new endopeptidase be referred to as
      endopeptidase 24.16B, while the originally described enzyme be referred to as
      endopeptidase 24.16A.

PMID- 7730309
TI  - Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in
      patients with GTP cyclohydrolase I deficiency.
AB  - GTP cyclohydrolase I is the first and rate-limiting enzyme for the biosynthesis
      of tetrahydrobiopterin in mammals. Previously, we reported three species of human
      GTP cyclohydrolase I cDNA in a human liver cDNA library (Togari, A., Ichinose,
      H., Matsumoto, S., Fujita, K., and Nagatsu, T. (1992) Biochem. Biophys. Res.
      Commun. 187, 359-365). Furthermore, very recently, we found that the GTP
      cyclohydrolase I gene is causative for hereditary progressive dystonia with
      marked diurnal fluctuation, also known as DOPA-responsive dystonia (Ichinose, H.,
      Ohye, T., Takahashi, E., Seki, N., Hori, T., Segawa, M., Nomura, Y., Endo, K.,
      Tanaka, H., Tsuji, S., Fujita, K., and Nagatsu, T. (1994) Nature Genetics 8, 236
      242). To clarify the mechanisms that regulate transcription of the GTP
      cyclohydrolase I gene and to generate multiple species of mRNA, we isolated
      genomic DNA clones for the human and mouse GTP cyclohydrolase I genes. Structural
      analysis of the isolated clones revealed that the GTP cyclohydrolase I gene is
      encoded by a single copy gene and is composed of six exons spanning approximately
      30 kilobases. We sequenced all exon/intron boundaries of the human and mouse
      genes. Structural analysis also demonstrated that the heterogeneity of GTP
      cyclohydrolase I mRNA is caused by an alternative usage of the splicing acceptor
      site at the sixth exon. The transcription start site of the mouse GTP
      cyclohydrolase I gene and the 5'-flanking sequences of the mouse and human genes
      were determined. We performed regional mapping of the mouse gene by fluorescence
      in situ hybridization, and the mouse GTP cyclohydrolase I gene was assigned to
      region C2-3 of mouse chromosome 14. We identified missense mutations in patients
      with GTP cyclohydrolase I deficiency and expressed mutated enzymes in Escherichia
      coli to confirm alterations in the enzyme activity.

PMID- 7730310
TI  - Structural basis of G protein specificity of human endothelin receptors. A study
      with endothelinA/B chimeras.
AB  - The endothelin (ET) family of peptides acts via two subtypes of guanine
      nucleotide-binding regulatory protein (G protein)-coupled receptors termed ETA
      and ETB. ET-1 stimulated cAMP formation in Chinese hamster ovary (CHO) cells
      stably expressing human wild-type ETA (CHO/hETA cells) while it inhibited cAMP
      formation in CHO cells expressing human wild-type ETB (CHO/hETB cells), and
      pharmacological evidence indicated that the opposite effects were due to the
      selective coupling of each receptor subtype with G alpha s/G alpha i. To find out
      a receptor domain(s) that determined the selective coupling, a series of chimeric
      receptors between hETA and hETB was expressed on CHO cells, and the effect of ET
      1 on cAMP formation in each cell line was tested. hETA with the replacement of
      second and/or third intracellular loop (ICLII and/or -III) to the corresponding
      region(s) of hETB failed to transmit the stimulatory effect of ET-1. hETB with
      the replacement of ICLIII to the corresponding region of hETA failed to transmit
      the inhibitory effect of ET-1. A chimeric receptor with ICLII of hETB and with
      ICLIII of hETA failed to transmit both effects. In cells expressing chimeric
      receptors with ICLII of hETA and with ICLIII of hETB, ET-1 inhibited cAMP
      formation while it stimulated cAMP formation when cells were pretreated with
      pertussis toxin. These results indicated the roles of ICLII and -III of hETR as a
      major determinant of the selective coupling of hETA and hETB with G alpha s/G
      alpha i, respectively. We also demonstrated that each receptor subtype expressed
      on the same cell could work independently, i.e. for hETA to activate G alpha s
      and for hETB to activate G alpha i, resulting in dose-dependent dual effects of
      ET-1 on cAMP formation.

PMID- 7730311
TI  - The appendage domain of alpha-adaptin is a high affinity binding site for
      dynamin.
AB  - Dynamin is a GTPase that appears to be required for endocytosis. Even though this
      molecule is known to be in surface-coated pits, the identity of the resident coat
      proteins that account for this localization is not known. Here we show that
      dynamin is one of three synaptic terminal proteins that bind with specificity to
      the appendage domain of alpha-adaptin. Binding is sensitive to both salt and pH
      levels but is not affected by nucleotides. Using recombinant dynamin expressed in
      SF9 cells, we estimate that the binding affinity is approximately 200 nM. Binding
      does not require GTP, and the GTPase activity of dynamin is not stimulated by
      this interaction. These results suggest that the COOH terminus of alpha-adaptin
      may be a domain within AP2 that mediates the initial interactions between dynamin
      and surface-coated pits. This may be an essential step in the regulation of
      coated pit budding.

PMID- 7730312
TI  - Use of a marked erythropoietin gene for investigation of its cis-acting elements.
AB  - To examine the function of conserved noncoding regions in the erythropoietin
      (Epo) gene, we have prepared clones and pools of Hep3B cells stably transfected
      with a marked 4.1-kilobase Epo gene and deletions thereof. The marked transcripts
      had single base substitutions at three sites in the coding portion of Exon 5,
      enabling them to be distinguished from endogenous Epo mRNA by ribonuclease
      protection and competitive polymerase chain reaction. The basal expression and
      hypoxic induction of the marked Epo gene that had no deletions were
      indistinguishable from that of the endogenous Epo gene. Likewise, deletion of
      conserved intervening sequence 1 had minimal effect on hypoxic induction. In
      contrast, a 3'-deletion that included the conserved 3'-enhancer element resulted
      in a substantial, but not complete, suppression of hypoxic induction while a 3'
      deletion downstream of the enhancer resulted in enhancement. A 188-base pair
      deletion of a conserved 3'-untranslated region in Exon 5 had minimal effect on
      hypoxic induction. However, the truncated Epo mRNA had a markedly prolonged half
      life (15 h) in comparison to the endogenous Epo mRNA (2.0 h) or the marked full
      length Epo mRNA (2.1 h). Further deletions in the 3'-UTR showed that a relatively
      small region of approximately 50 bases is responsible for the relatively rapid
      turnover of Epo mRNA. These experiments provide information on cis-acting
      elements of the Epo gene that cannot be obtained from conventional reporter gene
      transfection experiments.

PMID- 7730313
TI  - Nucleosome positioning by human Alu elements in chromatin.
AB  - Alu sequences are interspersed throughout the genomes of primate cells, occurring
      singly and in clusters around RNA polymerase II-transcribed genes. Because these
      repeat elements are capable of positioning nucleosomes in in vitro reconstitutes
      (Englander, E. W., Wolffe, A. P., and Howard, B. H. (1993) J. Biol. Chem. 268,
      19565-19573), we investigated whether they also influence in vivo chromatin
      structure. When assayed collectively using consensus sequence probes and native
      chromatin as template, Alu family members were found to confer rotational
      positioning on nucleosomes or nucleosome-like particles. In particular, a 10-base
      pair pattern of DNase I nicking that spanned the RNA polymerase III box A
      promoter motif extended upstream to cover diverse 5'-flanking sequences,
      suggesting that Alu repeats may influence patterns of nucleosome formation over
      neighboring regions. Computational analysis of a set of naturally occurring Alu
      sequences indicated that nucleosome positioning information is intrinsic to these
      elements. Inasmuch as local chromatin organization influences gene expression,
      the capacity of Alu sequences to affect chromatin structure as demonstrated here
      may help to clarify some features of these elements.

PMID- 7730314
TI  - Highly specific and efficient cleavage of squid tRNA(Lys) catalyzed by magnesium
      ions.
AB  - Two lysine isoacceptor tRNAs corresponding to the codons AAA and AAG,
      respectively, were isolated from squid (Loligo bleekeri), and their nucleotide
      sequences were determined. During this analysis, we discovered that the tRNA with
      the anticodon CUU was efficiently cleaved at a specific site in the presence of
      magnesium ions, whereas the tRNA with the anticodon UUU was not. Cleavage
      occurred almost exclusively at the phosphodiester linkage between G15 and D16
      (p16). The most remarkable feature of this cleavage reaction is that the end
      product was not a 2',3'-cyclic phosphate but was mainly a 3'-phosphate. Thus,
      this reaction was distinct from the well characterized cleavage of yeast
      tRNA(Phe) by lead and from reactions catalyzed by various other metalloribozymes.
      The presence of a cytidine residue at position 60 was required for efficient
      cleavage but was not crucial for the reaction, and the entire tRNA molecule had
      to be intact for this specific and efficient cleavage reaction. The present study
      provides evidence that there exists a new catalytic mechanism for cleavage of
      tRNA that exploits biologically ubiquitous ions rather than toxic, nonessential
      ions such as lead.

PMID- 7730315
TI  - Poliovirus protein 2C contains two regions involved in RNA binding activity.
AB  - Poliovirus protein 2C is involved in poliovirus RNA replication, although the
      exact function of 2C is still unknown. Recently, it was shown that 2C can be
      purified to high levels when expressed as a fusion protein with maltose-binding
      protein (MBP). Evidence was presented that 2C has ATPase and GTPase activities;
      preliminary results also indicated that 2C interacts with RNA (Rodriguez, P.L.,
      and Carrasco, L. (1993) J. Biol. Chem. 268, 8105-8110). In the present study, 20
      variants of 2C have been generated, and their NTPase and RNA binding activities
      were analyzed. Moreover, an easy procedure to obtain genuine 2C after factor Xa
      cleavage of an MBP2-2C fusion protein is described. This work has determined that
      2C has two regions involved in RNA binding: a NH2-terminal region located between
      amino acids 21 and 45 and a COOH-terminal region involving an Arg-rich region
      located between amino acids 312 and 319. Deletion of either the NH2- or COOH
      terminal RNA-binding region abolishes RNA binding. Deletion of an internal region
      of protein 2C that includes the nucleotide-binding motif does not affect RNA
      binding, whereas this deletion destroys ATPase and GTPase activities. Therefore,
      the NTPase activity and the RNA binding capacity of protein 2C are located in
      different regions of the molecule.

PMID- 7730316
TI  - Photoaffinity labeling of a peptide substrate to myosin light chain kinase.
AB  - The substrate binding properties of skeletal muscle myosin light chain kinase
      were investigated with a synthetic peptide containing the photoreactive amino
      acid p-benzoylphenylalanine (Bpa) incorporated amino-terminal of the
      phosphoacceptor serine (BpaKKRAARATSNVFA). When photolyzed at 350 nm, the peptide
      was cross-linked stoichiometrically to myosin light chain kinase in a
      Ca2+/calmodulin-dependent manner. Peptide incorporation into kinase inhibited
      light chain phosphorylation, and the loss of kinase activity was proportional to
      the extent of peptide incorporated. After peptide I was incorporated into myosin
      light chain kinase, it was partially phosphorylated in the absence of
      Ca2+/calmodulin. The extent of phosphorylation increased in the presence of
      Ca2+/calmodulin. The cross-linked photoadduct was digested, labeled peptides were
      purified by high performance liquid chromatography, and sites of covalent
      modification were determined by amino acid sequencing and analysis. The covalent
      modification in the catalytic core occurred on Ile-373 (66%) and in a peptide
      containing residues Asn-422 to Met-437 (14%), respectively. Lys-572 in the
      autoinhibitory region accounted for 20% of the incorporated label. The coincident
      covalent modification of the autoinhibitory domain suggests that it is located
      near the catalytic site. Based upon a model of the catalytic core, the substrate
      peptide is predicted to bind in the cleft between the two lobes of the kinase.
      The orientation of the substrate peptide on myosin light chain kinase is similar
      to the orientation of the substrate recognition fragment, but not the high
      affinity binding fragment, of inhibitor peptide of cAMP-dependent protein kinase
      in the catalytic subunit of the cAMP-dependent protein kinase.

PMID- 7730317
TI  - Processing of mouse proglucagon by recombinant prohormone convertase 1 and
      immunopurified prohormone convertase 2 in vitro.
AB  - The mouse tumor cell line alpha TC1-6 was used as a model system to examine the
      post-translational processing of proglucagon. Determination of the mouse
      preproglucagon cDNA sequence and comparison with the published sequences of rat
      and human preproglucagons revealed nucleic acid homologies of 89.1 and 84%,
      respectively, and amino acid homologies of 94 and 89.4%, respectively.
      Immunohistochemical analyses with antibodies directed against PC2 and glucagon
      colocalized both the enzyme and substrate within the same secretory granules. PC1
      was also immunolocalized in secretory granules. Cells were metabolically labeled
      with [3H]tryptophan, and extracts were analyzed by reverse-phase high pressure
      liquid chromatography. Radioactive peptides with retention times identical to
      those of synthetic peptide standards were recovered and subjected to peptide
      mapping to verify their identities. To determine the potential role of PC1 and
      PC2 in proglucagon processing, 3H-labeled proglucagon was incubated in vitro with
      recombinant PC1 and/or immunopurified PC2. Both enzymes cleaved proglucagon to
      yield the major proglucagon fragment, glicentin, and oxyntomodulin, whereas only
      PC1 released glucagon-like peptide-I from the major proglucagon fragment. Neither
      PC1 nor PC2 processed glucagon from proglucagon in vitro. These results suggest a
      potential role for PC1 and/or PC2 in cleaving several of the normal products,
      excluding glucagon, from the mouse proglucagon precursor.

PMID- 7730318
TI  - Isolation of a novel latent transforming growth factor-beta binding protein gene
      (LTBP-3).
AB  - This paper reports the molecular cloning of a novel gene in the mouse that shows
      structural similarities to the microfibril protein fibrillin and to the latent
      transforming growth factor-beta (TGF-beta) binding protein (LTBP), a component of
      the latent TGF-beta complex. The gene was initially isolated during a low
      stringency polymerase chain reaction screen of a NIH 3T3 cell cDNA library using
      primers that amplify a human fibrillin-1 epidermal growth factor-like repeat.
      Three lines of evidence suggest that the mouse gene is a third member of the LTBP
      gene family, which we designate LTBP-3. First, the deduced polypeptide, which
      consists of 15 epidermal growth factor-like repeats, 3 TGF binding protein
      repeats, and 2 proline- and glycine-rich sequences, shows 38.4% identity with
      LTBP-1 but only 27% identity with fibrillin-1. Second, the gene appears to be co
      expressed in developing mouse tissues with TGF-beta. Third, immunoprecipitation
      studies using mouse preosteoblast MC3T3-E1 cells and a specific anti-peptide
      polyclonal antiserum reveal that the mouse polypeptide forms a complex with the
      TGF-beta 1 precursor. Finally, we note that the LTBP-3 gene was recently
      localized to a distinct genetic locus (Li, X., Yin, W., Perez-Jurado, L.,
      Bonadio, J., and Francke, U. (1995) Mamm. Genome 6, 42-45). Identification of a
      third binding protein provides further insight into a mechanism by which latent
      TGF-beta complexes can be targeted to connective tissue matrices and cells.

PMID- 7730319
TI  - Compartmentalization of autocrine signal transduction pathways in Sis-transformed
      NIH 3T3 cells.
AB  - The transforming protein of simian sarcoma virus is homologous to the platelet
      derived growth factor (PDGF) B-chain. Fibroblasts transformed with simian sarcoma
      virus constitutively produce a growth factor that stimulates the endogenous
      tyrosine kinase of PDGF receptors in an autocrine manner. Autophosphorylation of
      PDGF receptors upon ligand stimulation provides binding sites for Src homology 2
      domains of intracellular signaling molecules, which thereby become activated. We
      have characterized the PDGF receptor-mediated signal transduction in NIH 3T3
      cells transformed with a PDGF B-chain cDNA (Sis 3T3 cells) in the absence and
      presence of suramin, a polyanionic compound that quenches PDGF-induced
      mitogenicity and reverts the transformed phenotype of the Sis 3T3 cells. Our data
      show that in the presence of suramin the general level of tyrosine
      phosphorylation was decreased. Nevertheless, autophosphorylated receptors
      complexed with substrates persisted in the cells. Suramin had no effect on
      activation of phosphatidylinositol 3'-kinase or on tyrosine phosphorylation of
      phospholipase C-gamma and GTPase-activating protein of Ras. On the other hand,
      kinase activation of Src and Raf-1, phosphorylation of protein-tyrosine
      phosphatase 1D/Syp and Shc, and complex formation with Grb2 were greatly
      diminished by suramin. A possible explanation for our findings is that different
      PDGF receptor-coupled signaling pathways are active in different structural or
      functional compartments in the cell. Those pathways that are not affected by
      suramin might elicit distinct cellular responses, which are not sufficient for
      growth and transformation.

PMID- 7730320
TI  - Distinct regions of Cu(I).ACE1 contact two spatially resolved DNA major groove
      sites.
AB  - The interaction between the Cu(I).ACE1 (CuACE1) transcription factor and its DNA
      binding site in the yeast metallothionein gene was studied by systematically
      altering the DNA sequence through base substitution, modification, and deletions
      as well as by altering the protein structure through chemical modification. We
      show here that CuACE1 is comprised of two distinct domains that contact DNA
      through minor groove interactions located between two major groove interaction
      sites. The minor groove interactions are shown to be critical for formation of a
      stable CuACE1.DNA complex. The NH2-terminal segment of ACE1 is shown to contact
      the 5'-most distal major groove site.

PMID- 7730321
TI  - Human signal recognition particle (SRP) Alu-associated protein also binds Alu
      interspersed repeat sequence RNAs. Characterization of human SRP9.
AB  - Nearly 1 million interspersed Alu elements reside in the human genome. Alu
      retrotransposition is presumably mediated by full-length Alu transcripts
      synthesized by RNA polymerase III, while some polymerase III-synthesized Alu
      transcripts undergo 3'-processing and accumulate as small cytoplasmic (sc) RNAs
      of unknown function. Interspersed Alu sequences also reside in the untranslated
      regions of some mRNAs. The Alu sequence is related to a portion of the 7SL RNA
      component of signal recognition particle (SRP). This region of 7SL RNA together
      with 9- and 14-kDa polypeptides (SRP9/14) regulates translational elongation of
      ribosomes engaged by SRP. Here we characterize human (h) SRP9 and show that it,
      together with hSRP14 (SRP9/14), forms the activity previously identified as Alu
      RNA-binding protein (RBP). The primate-specific C-terminal tail of hSRP14 does
      not appreciably affect binding to scAlu RNA. Kd values for three Alu-homologous
      scRNAs were determined using Alu RBP (SRP9/14) purified from HeLa cells. The Alu
      region of 7SL, scAlu, and scB1 RNAs exhibited Kd values of 203 pM, 318 pM, and
      1.8 nM, respectively. Finally, Alu RBP can bind with high affinity to synthetic
      mRNAs that contain interspersed Alus in their untranslated regions.

PMID- 7730322
TI  - A neutral galactocerebroside sulfate sulfatidase from mouse brain.
AB  - We have described an enzyme in brain that catabolizes galactocerebroside
      sulfatide with a pH optimum of 7.2. To our knowledge, this is the first
      description of a catabolic enzyme for sulfatide at a neutral pH. Activity at a
      neutral pH implies a non-lysosomal location for this sulfatidase.
      Galactocerebroside sulfate sulfatidase (n-sulfatidase) activity was not apparent
      in crude microsomal extracts and was detected following partial purification of
      the enzyme. This enzyme, n-sulfatidase, differs from other arylsulfatases in its
      M(r), inability to bind to concanavalin A, and substrate specificity; n
      sulfatidase was unable to hydrolyze p-nitrocatechol sulfate or estrone sulfate.
      The molecular mass of n-sulfatidase obtained by Sephacryl S-200 chromatography
      was 72 kDa, and the active fraction from this procedure was purified > 600-fold
      by isoelectric focusing. Following SDS-polyacrylamide gel electrophoresis, two
      bands were obtained with apparent molecular masses of 58 and 66 kDa. Enzyme
      activity was regenerated from both of these bands, with the 66-kDa band showing
      greater activity. The Km of the sulfatidase was determined as 5.8 x 10(-5) M. The
      pI of n-sulfatidase was 7.7 in contrast to the pI of 4.9 for the
      sulfotransferase. No requirement was found for Mg2+ or ATP for sulfatidase
      activity; vitamin K1 enhanced sulfatidase activity approximately 3.3-fold.
      Therefore, this enzyme may have a role in the pathogenesis of metachromatic
      leukodystrophy in which sulfatides accumulate in the nervous and other tissues
      and in myelination since sulfatides are an important component of myelin.

PMID- 7730323
TI  - Expression and function of the trehalase genes NTH1 and YBR0106 in Saccharomyces
      cerevisiae.
AB  - The biological function of the trehalose-degrading yeast enzyme neutral trehalase
      consists of the control of the concentration of trehalose, which is assumed to
      play a role in thermotolerance, in germination of spores, and in other life
      functions of yeast. Resequencing of the neutral trehalase gene NTH1 on chromosome
      IV resulted in the observation of two possible start codons (Kopp, M., Nwaka, S.,
      and Holzer, H. (1994) Gene (Amst.) 150, 403-404). We show here that only the most
      upstream start codon which initiates translation of the longest possible ORF is
      used for expression of NTH1 in vivo. A gene with 77% identity with NTH1, YBR0106,
      which was discovered during sequencing of chromosome II (Wolfe, K. H., and Lohan,
      A. J. E. (1994) Yeast 10, S41-S46), is shown here to be expressed into mRNA.
      Experiments with a mutant disrupted in the YBR0106 ORF showed, in contrast to a
      NTH1 deletion mutant, no changes in trehalase activity and in trehalose
      concentration. However, similar to the NTH1 gene a requirement of the intact
      YBR0106 gene for thermotolerance is demonstrated in experiments with the
      respective mutants. This indicates that the products of the likely duplicated
      YBR0106 gene and the NTH1 gene serve a heat shock protein function. In case of
      the YBR0106 gene, this is the only phenotypic feature found at present.

PMID- 7730324
TI  - Divergent insulin and platelet-derived growth factor regulation of focal adhesion
      kinase (pp125FAK) tyrosine phosphorylation, and rearrangement of actin stress
      fibers.
AB  - Insulin treatment of Chinese hamster ovary cells expressing high levels of the
      human insulin receptor resulted in the tyrosine dephosphorylation of the 125-kDa
      focal adhesion kinase (pp125FAK). The decrease in pp125FAK tyrosine
      phosphorylation paralleled a decrease in the cellular content of actin stress
      fibers, and these changes were independent of the extracellular matrix on which
      the cells were grown. The reduction in both pp125FAK tyrosine phosphorylation and
      actin stress fibers occurred in an insulin concentration-dependent manner, with
      significant effects at approximately 0.3 nM and a maximal effect at 3 nM.
      However, in the continuous presence of insulin, the decreases in the tyrosine
      phosphorylation state of pp125FAK and actin stress fiber content were transient.
      Maximal reduction of pp125FAK tyrosine phosphorylation was observed following 15
      min of insulin treatment, with a return to unstimulated control levels by 60 min.
      Similarly, actin stress fiber content was maximally reduced by 15 min of insulin
      treatment and fully recovered by 60 min. In contrast to insulin, platelet-derived
      growth factor stimulation increased actin stress fiber content and enhanced
      pp125FAK tyrosine phosphorylation. These data demonstrate a novel signaling role
      for insulin in inducing the tyrosine dephosphorylation of pp125FAK and a
      concomitant reorganization of actin stress fibers, which underlies at least one
      aspect of signaling divergence between the insulin and platelet-derived growth
      factor receptor tyrosine kinases.

PMID- 7730325
TI  - Identification of a nuclear factor-I family protein-binding site in the silencer
      region of the cartilage matrix protein gene.
AB  - Cartilage matrix protein (CMP) is synthesized by chondrocytes in a
      developmentally regulated manner. Here we have dissected promoter upstream
      elements involved in its transcriptional regulation. We show that although the 79
      base pair CMP minimal promoter is promiscuous, 1137 base pairs of 5'-flanking
      region are capable of directing tissue- and developmental stage-specific
      transcription when fused to a reporter gene. This results from two positive
      control regions which, in proliferating chondrocytes, relieve the repression
      mediated by two non-tissue-specific negative control regions. Characterization of
      the promoter proximal silencer by DNase I footprinting and gel shifts revealed
      the presence of two elements, SI and SII, which bound mesenchymal cell proteins.
      Methylation interference analysis indicated a gapped palindromic binding site
      similar to nuclear factor I (NF-I) family proteins within SI, but only a half
      site within SII. Gel shift assays with specific NF-I and mutated SI competitors,
      binding of recombinant NF-I, as well as supershift analysis with NF-I-specific
      antiserum verified the binding of NF-I family proteins to the SI element. Double
      stranded SI and SII oligonucleotides inserted in single copy in either
      orientation were found to repress both homologous and heterologous promoters upon
      transfection into mesenchymal cells. Transcriptional repression also occurred
      when a consensus NF-I site itself was fused to the CMP minimal promoter. We
      conclude that NF-I-related protein(s) can mediate transcriptional repression in
      cells of mesenchymal origin.

PMID- 7730326
TI  - Ligand-specific structural domains in the fibroblast growth factor receptor.
AB  - Two tandem immunoglobulin-like disulfide loops (Loops II and III) linked by a
      short connecting sequence in the ectodomain of the fibroblast growth factor
      receptor kinase compose the binding sites for glycosaminoglycan and fibroblast
      growth factor (FGF) ligands. Alternate splicing of exons IIIb and IIIc coding for
      the COOH-terminal half of Loop III confers high affinity for FGF-7 or FGF-2,
      respectively, on the fibroblast growth factor receptor ectodomain without effect
      on the binding of FGF-1. Here we show that a 139-amino acid fragment composed of
      Loop II, the inter-Loop II/III sequence, and a short segment of the NH2 terminus
      of Loop III is sufficient and near the minimal requirement for binding of FGF-1,
      FGF-2, and FGF-7. Extension of the fragment by five additional highly conserved
      residues (SD(P/A)QP) within a distinct constitutive structural domain (fl1) in
      Loop III restricts the binding of FGF-7 without effect on FGF-1 and FGF-2. Since
      the presence of exon IIIc in the full-length ectodomain does not change this
      ligand binding profile, we suggest that alternately spliced exon IIIc plays no
      active role in binding of the three ligands. In contrast, exon IIIb actively
      abrogates the restriction on the binding of FGF-7 and concurrently lowers the
      affinity for FGF-2.

PMID- 7730327
TI  - Alternately spliced NH2-terminal immunoglobulin-like Loop I in the ectodomain of
      the fibroblast growth factor (FGF) receptor 1 lowers affinity for both heparin
      and FGF-1.
AB  - Alternate splicing of a single exon encoding an NH2-terminal immunoglobulin (Ig)
      disulfide loop in the ectodomain of the fibroblast growth factor receptor (FGFR)
      types 1 and 2 results in alpha and beta isoforms that exhibit 3- and 2-Ig loops,
      respectively. Previously we demonstrated that alternately spliced Loop I has no
      independent ligand binding activity but is sufficiently interactive with the
      ligand- and heparin-binding site formed by Loops II and III to lower affinity for
      the same fibroblast growth factor (FGF) ligand. Here we show that a lower
      affinity of FGFR1 alpha for heparin parallels the lower affinity for FGF-1. A
      mutant of FGFR1 alpha in which the sequence between Loops I and II was deleted
      exhibits high affinity for both FGF-1 and heparin and other properties of the
      FGFR1 beta isoform, which include resistance to degradation by trypsin and
      display of specific antibody epitopes. This suggests that the interloop sequence
      facilitates the interaction of Loop I with Loops II and III. Lack of expression
      of both exons coding for Loop I and the sequence between Loops I and II in the
      FGFR2 gene characterizes rat prostate tumor cells, which exhibit a loss of the
      low affinity class of FGF receptors. Although the exon coding for the sequence
      between Loops I and II is alternately spliced in the FGFR2 beta isoform,
      coordinate expression with the exon coding for Loop I results in the functional
      differences between the FGFR alpha and FGFR beta variants.

PMID- 7730328
TI  - Identification and characterization of a novel cytokine-inducible nuclear protein
      from human endothelial cells.
AB  - Vascular endothelial cells undergo profound changes upon cellular activation
      including expression of a spectrum of cell activation-associated genes. These
      changes play important roles in many physiological and pathological events. By
      differential screening of a cDNA library prepared from interleukin-1 alpha and
      tumor necrosis factor-alpha-stimulated human dermal microvascular endothelial
      cells, we have identified a novel cytokine-inducible gene, designated as C-193.
      The compiled cDNA sequence of C-193 is 1901 base pairs long and shows no
      significant homology with any known gene sequence. Genomic DNA analysis revealed
      that C-193 is encoded by a single gene, which is conserved in different mammalian
      species. The C-193 gene was localized to human chromosome 10 by Southern blot
      analysis of somatic cell hybrids. Multiple AT-rich mRNA decay elements were
      identified in the 3'-untranslated region. C-193 mRNA expression was rapidly and
      transiently induced by treatment with interleukin-1 alpha or tumor necrosis
      factor-alpha, reached a peak of expression about 16 h post tumor necrosis factor
      alpha stimulation, and the induction of C-193 was protein synthesis independent.
      Lipopolysaccharide and cycloheximide were also potent inducers of C-193 mRNA.
      Therefore, C-193 represents a new addition to the primary response gene family.
      In vitro translation of C-193 yielded a 36-kDa protein product, consistent with
      the predicted open reading frame of 318 amino acids and a calculated molecular
      mass of 36 kDa for C-193 protein. The predicted protein sequence contains a basic
      amino acid cluster similar to a nuclear localization signal, four tandem repeats
      of ankyrin-like sequence, and multiple consensus protein phosphorylation sites. C
      193 was engineered with a FLAG tag at its carboxyl terminus and transiently
      expressed in COS cells. Consistent with the presence of a putative nuclear
      localization signal, the C-193-FLAG protein was localized to the nucleus of
      transfected COS cells by indirect immunofluorescence microscopy. C-193-FLAG
      prepared in vitro was capable of binding DNA cellulose. These results indicate
      that C-193 protein may play an important role in endothelial cell activation.

PMID- 7730329
TI  - A novel plasminogen activator from snake venom. Purification, characterization,
      and molecular cloning.
AB  - A novel plasminogen activator from Trimeresurus stejnegeri venom (TSV-PA) has
      been identified and purified to homogeneity. It is a single chain glycoprotein
      with an apparent molecular weight of 33,000 and an isoelectric point of pH 5.2.
      It specifically activates plasminogen through an enzymatic reaction. The
      activation of human native Glu-plasminogen by TSV-PA is due to a single cleavage
      of the molecule at the peptide bond Arg561-Val562. Purified TSV-PA, which
      catalyzes the hydrolysis of several tripeptide p-nitroanilide substrates, does
      not activate nor degrade prothrombin, factor X, or protein C and does not clot
      fibrinogen nor show fibrino(geno)lytic activity in the absence of plasminogen.
      The activity of TSV-PA was readily inhibited by phenylmethanesulfonyl fluoride
      and by p-nitrophenyl-p-guanidinobenzoate. Oligonucleotide primers designed on the
      basis of the N-terminal and the internal peptide sequences of TSV-PA were used
      for the amplification of cDNA fragments by polymerase chain reaction. This
      allowed the cloning of a full-length cDNA encoding TSV-PA from a cDNA library
      prepared from the venom glands. The deduced complete amino acid sequence of TSV
      PA indicates that the mature TSV-PA protein is composed of 234 amino acids and
      contains a single potential N-glycosylation site at Asn161. The sequence of TSV
      PA exhibits a high degree of sequence identity with other snake venom proteases:
      66% with the protein C activator from Agkistrodon contortrix contortrix venom,
      63% with batroxobin, and 60% with the factor V activator from Russell's viper
      venom. On the other hand, TSV-PA shows only 21-23% sequence similarity with the
      catalytic domains of u-PA and t-PA. Furthermore, TSV-PA lacks the sequence site
      that has been demonstrated to be responsible for the interaction of t-PA (KHRR)
      and u-PA (RRHR) with plasminogen activator inhibitor type 1.

PMID- 7730330
TI  - Rat antizyme inhibits the activity but does not promote the degradation of mouse
      ornithine decarboxylase in Trypanosoma brucei.
AB  - Ornithine decarboxylase (ODC) of African trypanosomes is an important target for
      anti-trypanosomal chemotherapy because of its remarkable stability in vivo. The
      in vivo activity and stability of mammalian ODC are regulated by polyamines.
      Polyamines induce antizyme, which inactivates ODC by tight association and
      promotes degradation of ODC by the mammalian 26 S proteasome. Here we found, in
      contrast to mammalian cells, that polyamines caused no reduction of ODC activity
      in Trypanosoma brucei. Mouse ODC expressed in T. brucei was also unaffected by
      exogenous polyamines, suggesting that a mammalian antizyme equivalent may be
      absent in T. brucei. The rat antizyme expressed in T. brucei was found capable of
      inhibiting mouse ODC activity by the formation of rat antizyme-mouse ODC complex.
      However, complex formation did not lead to degradation of mouse ODC in T. brucei.
      Further in vitro experiments suggested the presence of an inhibitory factor(s) in
      trypanosome, which interferes with the degradation of mouse ODC. We also
      demonstrated the presence of proteasomes in T. brucei. But the mobility of the
      trypanosomal proteasome on native gel is different from that of the mammalian
      proteasome. Thus, the absence of antizyme, the presence of inhibitory factor(s),
      and the differences between trypanosomal and mammalian proteasome may account for
      the stability of mouse ODC in T. brucei cells.

PMID- 7730331
TI  - Involvement of a pertussis toxin-sensitive G protein in the mitogenic signaling
      pathways of sphingosine 1-phosphate.
AB  - Sphingosine 1-phosphate, a sphingolipid metabolite, was previously reported to
      increase DNA synthesis in quiescent Swiss 3T3 fibroblasts and to induce transient
      increases in intracellular free calcium (Zhang, H., Desai, N. N., Olivera, A.,
      Seki, T., Brooker, G., and Spiegel, S. (1991) J. Cell Biol. 114, 155-167). In the
      present study, pretreatment of Swiss 3T3 fibroblasts with pertussis toxin reduced
      sphingosine 1-phosphate-induced DNA synthesis. Sphingosine 1-phosphate decreased
      cellular cAMP levels and also caused a drastic decrease in isoproterenol- and
      forskolin-stimulated cAMP accumulation. Pertussis toxin treatment prevented the
      inhibitory effect of sphingosine 1-phosphate on cAMP accumulation, suggesting
      that a pertussis toxin-sensitive Gi or Gi-like protein may be involved in
      sphingosine 1-phosphate-mediated inhibition of cAMP accumulation. Mitogenic
      concentrations of sphingosine 1-phosphate stimulated production of inositol
      phosphates which was inhibited by pertussis toxin, while the response to
      bradykinin was not affected. Furthermore, calcium release induced by sphingosine
      1-phosphate, but not by bradykinin, was also attenuated by pertussis toxin
      treatment. However, sphingosine 1-phosphate-induced phosphatidic acid
      accumulation was unaffected by pertussis toxin. The increase in specific DNA
      binding activity of activator protein-1, which was induced by treatment of
      quiescent Swiss 3T3 fibroblasts with sphingosine 1-phosphate, was also inhibited
      by pertussis toxin. These results suggest that some of the sphingosine 1
      phosphate-induced signaling pathways are mediated by G proteins that are
      substrates for pertussis toxin.

PMID- 7730332
TI  - Stimulation of HIV expression by intracellular calcium pump inhibition.
AB  - We have studied the role of intracellular calcium sequestration on human
      immunodeficiency virus (HIV) production by latently infected T-lymphocytic cells.
      Inhibition of the sarco-endoplasmic reticulum-type calcium transport ATPases by
      thapsigargin or cyclopiazonic acid induced activation of HIV production in the
      CEM-derived ACH-2 cells. An approximately 50% depletion of the thapsigargin
      sensitive calcium pools as measured fluorimetrically of Indo-loaded cells fully
      activated virus production. Viral activation was manifest by increases in soluble
      viral core p24 production, increases in cellular immunofluorescent staining for
      viral antigens, and increased viral transcription as measured by HIV long
      terminal repeat-directed expression of the chloramphenicol acetyltransferase
      reporter gene. Virus induction could be blocked in a dose-dependent manner by the
      calcium channel blocker econazole. Virus production by the Jurkat-derived HIV-1
      inducible J1.1 cells was not significantly stimulated by thapsigargin. These data
      indicate that intracellular calcium pool function is involved in the control of
      the transcription of proviral HIV in a cell type-specific manner within the T
      lymphoid lineage and that ACH-2 cells represent a useful model for the study of
      calcium dependent activation of the transcription of proviral HIV.

PMID- 7730333
TI  - Effects of two mutations detected in medium chain acyl-CoA dehydrogenase (MCAD)
      deficient patients on folding, oligomer assembly, and stability of MCAD enzyme.
AB  - We have used expression of human medium chain acyl-CoA dehydrogenase (MCAD) in
      Escherichia coli as a model system for dissecting the molecular effects of two
      mutations detected in patients with MCAD deficiency. We demonstrate that the R28C
      mutation predominantly affects polypeptide folding. The amounts of active R28C
      mutant enzyme produced could be modulated between undetectable to 100% of the
      wild-type control by manipulating the level of available chaperonins and the
      growth temperature. For the prevalent K304E mutation, however, the amounts of
      active mutant enzyme could be modulated only in a range from undetectable to
      approximately 50% of the wild-type, and the assembled mutant enzyme displayed a
      decreased thermal stability. Two artificially constructed mutants (K304Q and
      K304E/D346K) yielded clearly higher amounts of active MCAD enzyme than the K304E
      mutant but were also responsive to chaperonin co-overexpression and growth at low
      temperature. The thermal stability profile of the K304E/D346K double mutant was
      shifted to even lower temperatures than that of the K304E mutant, whereas that of
      the K304Q mutant was closely similar to the wild-type. Taken together, the
      results show that the K304E mutation affects (i) polypeptide folding due to
      elimination of the positively charged lysine and (ii) oligomer assembly and
      stability due to replacement of lysine 304 with the negatively charged glutamic
      acid.

PMID- 7730334
TI  - HU protein of Escherichia coli binds specifically to DNA that contains single
      strand breaks or gaps.
AB  - In this study, we have identified a protein in Escherichia coli that specifically
      binds to double-stranded DNA containing a single-stranded gap of one nucleotide.
      The gap-DNA binding (GDB) protein was purified to apparent homogeneity. The
      analysis of the amino-terminal sequencing of the GDB protein shows two closely
      related sequences we identify as the alpha and beta subunits of the HU protein.
      Furthermore, the GDB protein is not detected in the crude extract of an E. coli
      double mutant strain hupA hupB that has no functional HU protein. These results
      led us to identify the GDB protein as the HU protein. HU binds strongly to double
      stranded 30-mer oligonucleotides containing a nick or a single-stranded gap of
      one or two nucleotides. Apparent dissociation constants were measured for these
      various DNA duplexes using a gel retardation assay. The KD(app) values were 8 nM
      for the 30-mer duplex that contains a nick and 4 and 2 nM for those that contain
      a 1-or a 2-nucleotide gap, respectively. The affinity of HU for these ligands is
      at least 100-fold higher than for the same 30-mer DNA duplex without nick or gap.
      Other single-stranded breaks or gaps, which are intermediate products in the
      repair of abasic sites after incision by the Fpg, Nth, or Nfo proteins, are also
      preferentially bound by the HU protein. Due to specific binding to DNA strand
      breaks, HU may play a role in replication, recombination, and repair.

PMID- 7730335
TI  - A 110-amino acid region within the A1-domain of coagulation factor VIII inhibits
      secretion from mammalian cells.
AB  - Factor VIII is the coagulation factor deficient in the X-chromosome-linked
      bleeding disorder hemophilia A. Factor VIII is homologous to blood coagulation
      factor V, both having a domain structure of A1-A2-B-A3-C1-C2. Previous
      transfection studies demonstrated that factor VIII is 10-fold less efficiently
      expressed than the homologous coagulation factor, factor V. The inefficient
      expression correlated with interaction of the factor VIII primary translation
      product with the protein chaperonin BiP in the lumen of the endoplasmic
      reticulum. In contrast, factor V was not detected in association with BiP and was
      secreted efficiently. To determine whether specific amino acid sequences within
      factor VIII inhibit secretion, we have studied the secretion of factor VIII
      deletion and factor VIII/factor V chimeric proteins upon transient transfection
      of COS-1 monkey cells. A chimeric factor VIII protein that contained the A1- and
      A2-domains of factor V was secreted with a similar efficiency as wild-type factor
      V, whereas the complementary chimera having the A1- and A2-domains of factor VIII
      was secreted with low efficiency, similar to wild-type factor VIII. These results
      suggested that sequences within the A1- and A2-domains were responsible for the
      low secretion efficiency of factor VIII. Secretion of A1-domain-deleted factor
      VIII was increased approximately 10-fold compared to wild-type factor VIII or A2
      domain-deleted factor VIII. Expression of the factor VIII A1-domain alone did not
      yield secreted protein, whereas expression of the factor VIII A2-domain alone or
      the factor V A1-domain or A2-domain alone directed synthesis of secreted protein.
      Secretion of a hybrid in which the carboxyl-terminal 110 amino acids of the A1
      domain were replaced by homologous sequences from the factor V A1-domain was also
      increased 10-fold compared to wild-type factor VIII, however, the secreted
      protein was not functional and the heavy and light chains were not associated.
      These results localize a 110-amino acid region within the A1-domain that inhibits
      factor VIII secretion. This region is clustered with multiple short peptide
      sequences that have potential to bind BiP.

PMID- 7730336
TI  - Activating transcription factor 1 and cyclic AMP response element modulator can
      modulate the activity of the immunoglobulin kappa 3' enhancer.
AB  - Previously we determined that the immunoglobulin kappa 3' enhancer (kappa E3')
      contains at least two functional DNA sequences (PU.1/NF-EM5 and E2A) within its
      132-base pair active core. We have determined that the activities of these two
      sequences are insufficient to account for the entire activity of the 132-base
      pair core. Using site-directed linker scan mutagenesis across the core fragment
      we identified several additional functional sequences. We used one of these
      functional sequences to screen a lambda gt11 cDNA expression library resulting in
      the isolation of cDNA clones encoding the transcription factors ATF-1 (activating
      transcription factor) and CREM (cyclic AMP response element modulator). Because
      ATF-1 and CREM are known to bind to cAMP response elements (CRE), this functional
      sequence was named the kappa E3'-CRE. We show that dibutyryl cAMP can increase
      kappa E3' enhancer activity, and in transient expression assays ATF-1 caused a 4
      5-fold increase in the activity of the core enhancer while CREM-alpha expression
      resulted in repression of enhancer activity. RNA analyses showed increased levels
      of ATF-1 mRNA during B cell development and some changes in CREM transcript
      processing. By joining various fragments of the kappa E3' enhancer to the kappa
      E3'-CRE, we observed that the kappa E3'-CRE can synergistically increase
      transcription in association with the PU.1/NF-EM5 binding sites, suggesting a
      functional interaction between the proteins that bind to these DNA sequences.
      Consistent with this possibility, we found that ATF-1 and CREM can physically
      interact with PU.1. The isolation of activator and repressor proteins that bind
      to the kappa E3'-CRE may relate to previous conflicting results concerning the
      role of the cAMP signal transduction pathway in kappa gene transcription.

PMID- 7730337
TI  - Structure and regulation of the gene encoding the neuron-specific protein kinase
      C substrate neurogranin (RC3 protein).
AB  - A 13-kilobase pair genomic DNA encoding a 78-amino acid brain-specific calmodulin
      binding protein kinase C (PKC) substrate, neurogranin (Ng/RC3; also known as RC3
      or p17), has been sequenced. The Ng/RC3 gene is composed of four exons and three
      introns, with the protein-coding region located in the first and second exons.
      This gene was found to have multiple transcriptional start sites clustered within
      20 base pairs (bp); it lacks the TATA, GC, and CCAAT boxes in the proximal
      upstream region of the start sites. The promoter activity was characterized by
      transfection of 293 cells with nested deletion mutants of the 5'-flanking region
      fused to the luciferase reporter gene. A minimal construct containing bp +11 to
      +256 was nearly as active as that covering bp -1508 to +256, whereas a shorter
      one covering bp +40 to +256 had a greatly reduced activity. Between bp +11 and
      +40 lies a 12-nucleotide sequence (CCCCGCCCACCC) containing overlapping binding
      sites for AP2 (CCGCCCACCC) and SP1 (CCCGCC); this region may be important for
      conferring the basal transcriptional activity of the Ng/RC3 gene. The expression
      of a Ng/RC3-luciferase fusion construct (-1508/+256) in transfected 293 cells was
      stimulated by phorbol 12-myristate 13-acetate (PMA), but not by cAMP, arachidonic
      acid, vitamin D, retinoic acid, or thyroxines T3 and T4. PMA caused a 2-4-fold
      stimulation of all the reporter gene constructs ranging from +11/+256 to 
      1508/+256. The stimulatory effects of PMA could be magnified by cotransfection
      with both Ca(2+)-dependent and -independent phorbol ester-binding PKC-alpha, 
      beta I, -beta II, -gamma, -delta, and -epsilon cDNAs, but not by non-phorbol
      ester-binding PKC-zeta cDNA. The Ng/RC3 and PKC-gamma genes have a similar
      expression pattern in the brain during development. These two genes share at
      least four conserved sequence segments 1.5 kilobase pair upstream from their
      transcriptional start sites and a gross similarity in that they possess several
      AT-rich segments within bp -550 to -950. A near homogeneous 20-kDa DNA-binding
      protein purified from rat brain was able to bind to these AT-rich regions of both
      Ng/RC3 and PKC-gamma genes with footprints containing ATTA, ATAA, and AATA
      sequences.

PMID- 7730338
TI  - Overproduction and physical characterization of SoxR, a [2Fe-2S] protein that
      governs an oxidative response regulon in Escherichia coli.
AB  - SoxR protein governs the soxRS (superoxide response) regulon of Escherichia coli
      by becoming a transcriptional activator when the cells are exposed to compounds
      that mediate univalent redox reactions, many of which produce superoxide as a by
      product. SoxR was overproduced and purified to near homogeneity from a strain
      bearing an expression vector. It could bind specifically to the soxS operator
      even in the absence of RNA polymerase. The aerobically purified protein, which is
      readily autooxidized, could activate the transcription of soxS DNA even without
      exposure to known inducing agents. SoxR is a globular homodimer. It contains one
      [2Fe-2S] cluster per polypeptide chain, as demonstrated by optical and EPR
      spectroscopy combined with stoichiometric analysis of iron content, unpaired
      electron-spin density, and reduction by dithionite. The protein is active in its
      oxidized ([2Fe-2S]2+) state. The presence of a prosthetic group capable of
      univalent redox reactions may help to explain the activation of the regulon in
      vivo by compounds that can mediate such reactions.

PMID- 7730339
TI  - The gene structure and organization of mouse PG-M, a large chondroitin sulfate
      proteoglycan. Genomic background for the generation of multiple PG-M transcripts.
AB  - We previously showed not only the presence of multiple RNA transcripts of
      different sizes encoding the core protein of mouse PG-M, but also their tissue
      dependent expression. Major causes for the multiple forms were found to be due to
      alternative usage of the two different chondroitin sulfate attachment domains
      (alpha and beta). In this study, genomic DNA analysis has revealed that these
      domains are encoded by two large exons, exon VII (2880 base pairs) and exon VIII
      (5229 base pairs). The splice sites of these two exons were consistent with the
      occurrence of alternative splicing without frameshift. Furthermore, the mouse PG
      M gene was shown to have four distinct polyadenylation signals and three
      candidates for the transcription initiation site as well. These genomic
      structural variations may contribute to the multiplicity of PG-M transcripts.
      Northern hybridization analysis showed that at least three different transcripts
      were generated by different usage of the distinct polyadenylation signals.

PMID- 7730340
TI  - Interaction of the P-glycoprotein multidrug transporter with peptides and
      ionophores.
AB  - P-glycoprotein functions as an ATP-driven active efflux pump for many cytotoxic
      drugs. We now show that hydrophobic peptides and ionophores also interact with
      the multidrug transporter. Multidrug-resistant cells are cross-resistant to
      several hydrophobic peptides and ionophores, but not to some other membrane
      active species. Linear peptides, cyclic peptides, and ionophores stimulated the
      ATPase activity of P-glycoprotein in plasma membrane vesicles by up to 2.5-fold.
      Drugs and chemosensitizers were able to block P-glycoprotein ATPase stimulation
      by verapamil, however, peptides and ionophores (with the exception of
      cyclosporine A) were unable to do so. Peptides and ionophores also effectively
      inhibited ATP-dependent drug transport by P-glycoprotein in plasma membrane
      vesicles. The median effect analysis was used to extract quantitative parameters
      from the drug transport inhibition data. Unlike drug substrates and cyclic
      peptides, linear peptides did not inhibit photoaffinity labeling of P
      glycoprotein by [3H]azidopine. Taken together, these results indicate that
      certain hydrophobic peptides and ionophores are P-glycoprotein substrates,
      however, they affect the transporter in a different manner from drugs. Linear
      peptides interact with P-glycoprotein at a site distinct from those for verapamil
      and azidopine, whereas the interaction site for cyclic peptides and ionophores
      appears to be linked to these sites to varying degrees. Export of hydrophobic
      peptides may be an important physiological function of P-glycoprotein.

PMID- 7730341
TI  - Changing patterns of transcriptional and post-transcriptional control of beta-F1
      ATPase gene expression during mitochondrial biogenesis in liver.
AB  - To elucidate the mechanisms that regulate the expression of nuclear genes during
      biogenesis of mammalian mitochondria, the expression pattern of the beta-subunit
      of the ATP synthase gene has been characterized in rat liver between day 20 in
      utero and 12 weeks postnatal. The parallelism existing between transcriptional
      activity of the gene and the amount of beta-F1-ATPase protein in liver indicates
      that proliferation of mitochondria is controlled at the transcriptional level. On
      the other hand, an increased stability (4-5-fold) of beta-F1-ATPase mRNA during
      early neonatal life as well as a rapid postnatal activation of translation rates
      affecting mitochondrial proteins appear to control mitochondrial differentiation.
      Immunoelectron microscopy of the F1-ATPase complex during liver development
      revealed that the rapid postnatal increase in the in vivo rate of F1-ATPase
      synthesis was mostly used for functional differentiation of pre-existing
      organelles (Valcarce, C., Navarrete, R. M., Encabo, P., Loeches, E., Satrustegui,
      J., and Cuezva, J. M. (1988) J. Biol Chem. 263, 7767-7775). The findings support
      that beta-F1-ATPase mRNA decay is developmentally regulated in liver, indicating
      that gene expression is also controlled at this level during physiological
      transitions that affect biogenesis of mitochondria.

PMID- 7730342
TI  - Identification by targeted differential display of an immediate early gene
      encoding a putative serine/threonine kinase.
AB  - Fibroblast growth factor (FGF)-1 mitogenic signal transduction is mediated in
      part by gene products that are specifically expressed in response to cell surface
      receptor binding and activation. We have used a targeted differential display
      method to identify FGF-1-inducible genes in murine NIH 3T3 fibroblasts. Here we
      report that one of these genes is predicted to encode a novel serine/threonine
      specific protein kinase. This putative kinase has been named Fnk, for FGF
      inducible kinase. The deduced Fnk amino acid sequence has 49, 36, 33, 32, and 22%
      overall identity to mouse serum-inducible kinase (Snk), mouse polo-like kinase
      (Plk), Drosophila polo, Saccharomyces Cdc5, and mouse Snk/Plk-akin kinase (Sak),
      respectively. These proteins are all members of the polo subfamily of
      structurally related serine/threonine kinases. The Plk, polo, Cdc5, and Sak
      kinases are required for cell division. FGF-1 induction of Fnk mRNA expression is
      first detected at 30 min after mitogen addition, reflects transcriptional
      activation, and does not require de novo protein synthesis. FGF-2, platelet
      derived growth factor-BB, calf serum, or phorbol myristate acetate treatment of
      quiescent cells also induces fnk gene expression. Fnk mRNA is expressed in vivo
      in a tissue-specific manner, with relatively high levels detected in newborn and
      adult mouse skin. These results indicate that Fnk may be a transiently expressed
      protein kinase involved in the early signaling events required for growth factor
      stimulated cell cycle progression.

PMID- 7730343
TI  - Lumenal orientation and post-translational modifications of the liver microsomal
      11 beta-hydroxysteroid dehydrogenase.

PMID- 7730344
TI  - Carbohydrate recognition by a natural killer cell receptor, Ly-49C.
AB  - Ly-49 represents a family of type II transmembrane proteins containing C-type
      lectin domains. At least two members of the Ly-49 family, namely Ly-49A and Ly
      49C, are expressed by distinct subsets of natural killer cells and bind to class
      I major histocompatibility complex antigens on the surface of target cells. In
      this report we have established that Ly-49C mediates carbohydrate recognition.
      The sulfated glycans fucoidan, lambda-carrageenan, and dextran sulfate were found
      to be potent inhibitors of Ly-49C-mediated cell adhesion, whereas other
      polysaccharides of similar size, charge, or sulfate content were noninhibitory.
      All of the polysaccharides which inhibited Ly-49C adhesion also blocked the
      binding of the antibody 5E6 to Ly-49C-expressing COS cells, confirming the direct
      protein-carbohydrate interaction. The enzymatic removal of specific carbohydrates
      from the target cell surface has shown that Ly-49C-mediated adhesion is not
      sialic acid-dependent, but is significantly decreased following fucosidase
      treatment. These results suggest an important role for carbohydrate recognition
      by natural killer cell receptors.

PMID- 7730345
TI  - Membrane depolarization prevents cell invasion by Bordetella pertussis adenylate
      cyclase toxin.
AB  - Adenylate cyclase toxin from Bordetella pertussis is a 177-kDa calmodulin
      activated enzyme that has the ability to enter eukaryotic cells and convert
      endogenous ATP into cAMP. Little is known, however, about the mechanism of cell
      entry. We now demonstrate that intoxication of cardiac myocytes by adenylate
      cyclase toxin is driven and controlled by the electrical potential across the
      plasma membrane. The steepness of the voltage dependence of intoxication is
      comparable with that previously observed for the activation of K+ and Na+
      channels of excitable membranes. The voltage-sensitive process is downstream from
      toxin binding to the cell surface and appears to correspond to the translocation
      of the catalytic domain across the membrane.

PMID- 7730346
TI  - Critical role of a conserved intramembrane tyrosine residue in angiotensin II
      receptor activation.
AB  - The rat type 1a (AT1a) angiotensin II (Ang II) receptor contains a highly
      conserved tyrosine residue in the fifth transmembrane region that is present in
      most G protein-coupled receptors. The role of this amino acid in AT1 receptor
      activation was analyzed in a mutant receptor (Y215F) created by replacing Tyr215
      with phenylalanine. The mutant receptor was highly expressed in transfected COS-7
      cells, and its binding affinity for the peptide antagonist [Sar1,Ile8]Ang II was
      similar to that of the wild type receptor. Although the structural integrity of
      the peptide ligand binding domain was preserved in the Y215F mutant receptor, its
      affinity for the native agonist, Ang II, was significantly reduced. Also, whereas
      guanosine 5'-3-O-(thio)triphosphate markedly reduced Ang II binding to the wild
      type receptor, it had little effect on agonist binding to the mutant receptor.
      Agonist-induced internalization of the mutant receptor was also impaired, and its
      ability to mediate inositol phosphate responses to Ang II stimulation was
      abolished. The concomitant decreases in receptor internalization and G protein
      mediated signaling of the Y215F mutant receptor indicate that Tyr215 has a
      critical role in AT1 receptor activation. In view of its conservation among
      members of the seven transmembrane domain receptor superfamily, this residue is
      likely to be of general importance in signal transduction from G protein-coupled
      receptors.

PMID- 7730347
TI  - Chromatographic resolution of an intracellular calcium influx factor from
      thapsigargin-activated Jurkat cells. Evidence for multiple activities influencing
      calcium elevation in Xenopus oocytes.
AB  - Acid extracts of thapsigargin-stimulated Jurkat cells revealed both intracellular
      and extracellular activities stimulating Ca(2+)-dependent Cl- currents on Xenopus
      laevis oocytes. Chromatographic fractionation of these extracts on gel filtration
      separated two active fractions of M(r) approximately 600 and 400. Moreover, the
      M(r) 600 fraction exhibited both intracellular and extracellular activities.
      However, the intracellular activity was absent from extracts of unstimulated
      Jurkat cells, suggesting its production was stimulated by thapsigargin. The
      further purification of this fraction by high performance thin layer
      chromatography resolved a single fraction which was active only on microinjection
      and which required calcium entry for activation of current responses. These
      results suggest that a single authentic calcium influx factor can be resolved by
      purification from confounding activities detected in crude acid extracts.

PMID- 7730348
TI  - Vascular endothelial growth factor increases urokinase receptor expression in
      vascular endothelial cells.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic factor and
      endothelial cell-specific mitogen that stimulates urokinase-type plasminogen
      activator (uPA) activity in vascular endothelial cells. Here, we report that VEGF
      increases the high affinity binding of uPA to the same cells and that this
      binding is prevented by a peptide corresponding to the uPA receptor (uPAR)
      binding growth factor-like domain of uPA. Ligand cross-linking, ligand blotting,
      and uPA-Sepharose affinity chromatography revealed an increase in a cell surface
      uPA binding protein that corresponds to the uPAR on the basis of its affinity for
      uPA, M(r) of 50,000-55,000, and phosphatidylinositol-specific phospholipase C
      sensitivity. By Scatchard analysis, VEGF increased the number of uPAR molecules
      by 2.8-3.5-fold and concomitantly decreased their affinity for uPA. By northern
      blotting uPAR mRNA was increased in a dose- and time-dependent manner in response
      to VEGF. Taken together, these findings demonstrate that VEGF-induced
      angiogenesis is accompanied by increased uPAR expression and uPA activity on the
      endothelial cell surface. These observations are consistent with the notion that
      the uPA-uPAR interaction facilitates cellular invasion.

PMID- 7730349
TI  - Kinetic characterization of the proteinase binding defect in a reactive site
      variant of the serpin, antithrombin. Role of the P1' residue in transition-state
      stabilization of antithrombin-proteinase complex formation.
AB  - To elucidate the role of the P1' residue of the serpin, antithrombin (AT), in
      proteinase inhibition, the source of the functional defect in a natural Ser-394-
      >Leu variant, AT-Denver, was investigated. AT-Denver inhibited thrombin, Factor
      IXa, plasmin, and Factor Xa with second order rate constants that were 430-, 120
      , 40-, and 7-fold slower, respectively, than those of native AT, consistent with
      an altered specificity of the variant inhibitor for its target proteinases. AT
      Denver inhibited thrombin and Factor Xa with nearly equimolar stoichiometries and
      formed SDS-stable complexes with these proteinases, indicating that the
      diminished inhibitor activity was not due to an enhanced turnover of the
      inhibitor as a substrate. Binding and kinetic studies showed that heparin binding
      to AT-Denver as well as heparin accelerations of AT-Denver-proteinase reactions
      were normal, consistent with the P1' mutation not affecting the heparin
      activation mechanism. Resolution of the two-step reaction of AT-Denver with
      thrombin revealed that the majority of the defective function was localized in
      the second reaction step and resulted from a 190-fold decreased rate constant for
      conversion of a noncovalent proteinase-inhibitor encounter complex to a stable,
      covalent complex. Little or no effects of the mutation on the binding constant
      for encounter complex formation or on the rate constant for stable complex
      dissociation were evident. These results support a role for the P1' residue of
      antithrombin in transition-state stabilization of a substrate-like attack of the
      proteinase on the inhibitor-reactive bond following the formation of a proteinase
      inhibitor encounter complex but prior to the conformational change leading to the
      trapping of proteinase in a stable, covalent complex. Such a role indicates that
      the P1' residue does not contribute to thermodynamic stabilization of AT
      proteinase complexes and instead favors a kinetic stabilization of these
      complexes by a suicide substrate reaction mechanism.

PMID- 7730350
TI  - L-aspartate association contributes to rate limitation and induction of the T-->R
      transition in Escherichia coli aspartate transcarbamoylase. Equilibrium exchanges
      and kinetic isotope effects with a Vmax-enhanced mutant, Asp-236-->Ala.
AB  - Equilibrium isotope exchange kinetics (EIEK) and kinetic isotope effects have
      been used to determine the mechanistic basis for the altered kinetic
      characteristics of a mutant version of Escherichia coli aspartate
      transcarbamylase in which Asp-236 of the catalytic chain is replaced by alanine
      (Asp-236-->Ala). The [14C]Asp<--> N-carbamyl-L-aspartate (CAsp) and [14C]CP<-
      >CAsp exchange rates, observed as a function of various reactant-product pairs,
      exhibited dramatic increases in maximal rates, along with decreases in substrate
      half-saturation values and cooperativity. The carbon kinetic isotope effect, 13C
      versus 12C at the carbonyl group of carbamoyl phosphate, for the Asp-236-->Ala
      enzyme decreased toward unity as [Asp] increased, as observed for the wild-type
      enzyme. Both the kinetic isotope effects and EIEK results indicate that the Asp
      236-->Ala enzyme operates by the same ordered kinetic mechanism as the wild-type
      enzyme. Although activation effects by ATP and N-phosphonacetyl-L-aspartate are
      lost, inhibition by CTP was apparent in equilibrium exchanges. Simulation of the
      EIEK data indicated that the best fit to the observed changes in saturation
      curves was obtained by preferentially increasing the rate of the T-->R
      transition, kappa T-->R, thereby destabilizing the T-state and increasing the
      equilbrium constant for the T<-->R transition. A multistep model for Asp bindng
      to aspartate transcarbamoylase is proposed, in which Asp induces the initial
      conformational changes that in turn trigger the T-->R transition, followed by
      stepwise filling of the remaining active sites.

PMID- 7730351
TI  - Mechanisms of DNA demethylation in chicken embryos. Purification and properties
      of a 5-methylcytosine-DNA glycosylase.
AB  - We have previously shown that in developing chicken embryos and differentiating
      mouse myoblasts, the demethylation of 5-metCpGs occurs through the replacement of
      5-methylcytosine by cytosine (Jost, J. P. (1993) Proc. Natl. Acad. Sci. U.S.A.
      90, 4685-4688; Jost, J. P. & Jost, Y.C. (1994) J. Biol. Chem. 269, 10040-10043).
      We have now purified over 30,000-fold a 5-methylcytosine-DNA glycosylase from 12
      day-old chicken embryos. The enzyme copurifies with a mismatch-specific thymine
      DNA glycosylase and an apyrimidic-endonuclease. The reaction product of the
      highly purified 5-methylcytosine-DNA glycosylase is 5-methylcytosine. The
      copurified apyrimidic-endonuclease activity cleaves 3' from the apyrimidic sugar.
      A 52.5-kDa peptide, isolated as a single band from preparative SDS-polyacrylamide
      gels, has both the 5-methylcytosine-DNA glycosylase and the mismatch-specific
      thymine-DNA glycosylase activities. 5-Methylcytosine-DNA glycosylase has an
      apparent pI of 5.5-7.5 and maximal activity between pH 6.5 and 7.5. The Km for
      hemimethylated oligonucleotide substrate is 8 x 10(-8) M with a Vmax of 4 x 10(
      11) mol/h/micrograms proteins. 5-Methylcytosine-DNA glycosylase binds equally
      well to methylated and non-methylated DNA. The enzyme reacts six times faster
      with the hemimethylated DNA than with the same bifilarly methylated DNA sequence,
      and single-stranded methylated DNA is not a substrate. The action of the enzyme
      is distributive.

PMID- 7730352
TI  - Isolation and characterization of the human tissue transglutaminase gene
      promoter.
AB  - Tissue transglutaminase belongs to a family of calcium-dependent enzymes, the
      transglutaminases that catalyze the covalent cross-linking of specific proteins
      by the formation of epsilon (gamma-glutamyl)lysine isopeptide bonds. The goal of
      this study has been the isolation and characterization of the human tissue
      transglutaminase gene promoter. Genomic DNA clones, spanning the 5' region of the
      gene, were isolated and the structure of the 5'-end of the human tissue
      transglutaminase gene was determined. 1.74 kilobases of flanking DNA were
      sequenced and were found to contain a TATA box element (TATAA), a CAAT box
      element (GGACAAT), a series of potential transcription factor-binding sites (AP1,
      SP1, interleukin-6 response element), and a glucocorticoid response elements.
      Transient transfection experiments showed that this DNA fragment included a
      functional promoter, which is constitutively active in multiple cell types.

PMID- 7730353
TI  - Structural and functional analysis of the metal-binding sites of Clostridium
      thermocellum endoglucanase CelD.
AB  - Crystallographic analysis indicated that Clostridium thermocellum endoglucanase
      CelD contained three Ca(2+)-binding sites, termed A, B, and C, and one Zn(2+)
      binding site. The protein contributed five, six, and three of the coordinating
      oxygen atoms present at sites A, B, and C, respectively. Proteins altered by
      mutation in site A (CelDD246A), B (CelDD361A), or C (CelDD523A) were compared
      with wild type CelD. The Ca(2+)-binding isotherm of wild type CelD was compatible
      with two high affinity sites (Ka = 2 x 10(6) M-1) and one low affinity site (Ka <
      10(5) M-1). The Ca(2+)-binding isotherms of the mutated proteins showed that
      sites A and B were the two high affinity sites and that site C was the low
      affinity site. Atomic absorption spectrometry confirmed the presence of one
      tightly bound Zn2+ atom per CelD molecule. The inactivation rate of CelD at 75
      degrees C was decreased 1.9-fold upon increasing the Ca2+ concentration from 2 x
      10(-5) to 10(-3) M. The Km of CelD was decreased 1.8-fold upon increasing the
      Ca2+ concentration from 5 x 10(-6) to 10(-4) M. Over similar ranges of
      concentration, Ca2+ did not affect the thermostability nor the kinetic properties
      of CelDD523A. These findings suggest that Ca2+ binding to site C stabilizes the
      active conformation of CelD in agreement with the close vicinity of site C to the
      catalytic center.

PMID- 7730354
TI  - In vitro assembly of the core catalytic complex of the chloroplast ATP synthase.
AB  - The regulatory gamma subunit and an alpha beta complex were isolated from the
      catalytic F1 portion of the chloroplast ATP synthase. The isolated gamma subunit
      was devoid of catalytic activity, whereas the alpha beta complex exhibited a very
      low ATPase activity (approximately 200 nmol/min/mg of protein). The alpha beta
      complex migrated as a hexameric alpha 3 beta 3 complex during ultracentrifugation
      and gel filtration but reversibly dissociated into alpha and beta monomers after
      freezing and thawing in the presence of ethylenediamine tetraacetic acid and in
      the absence of nucleotides. Conditions are described in which the gamma and alpha
      beta preparations were combined to rapidly and efficiently reconstitute a fully
      functional catalytic core enzyme complex. The reconstituted enzyme exhibited
      normal tight binding and sensitivity to the inhibitory epsilon subunit and to the
      allosteric inhibitor tentoxin. However, neither the alpha beta complex nor the
      isolated gamma subunit alone could bind the epsilon subunit or tentoxin with high
      affinity. Similarly, high affinity binding sites for ATP and ADP, which are
      characteristic of the core alpha 3 beta 3 gamma enzyme, were absent from the
      alpha beta complex. The results indicate that when the gamma subunit binds to the
      alpha beta complex, it induces a three-dimensional conformation in the enzyme,
      which is necessary for tight binding of the inhibitors and for high-affinity,
      asymmetric nucleotide binding.

PMID- 7730355
TI  - Concerted action of the high affinity calcium binding sites in skeletal muscle
      troponin C.
AB  - Mutants of each of the four divalent cation binding sites of chicken skeletal
      muscle troponin C (TnC) were constructed using site-directed mutagenesis to
      convert Asp to Ala at the first coordinating position in each site. With a view
      to evaluating the importance of site-site interactions both within and between
      the N- and C-terminal domains, in this study the mutants are examined for their
      ability to associate with other components of the troponin-tropomyosin regulatory
      complex and to regulate thin filaments. The functional effects of each mutation
      in reconstitution assays are largely confined to the domain in which it occurs,
      where the unmutated site is unable to compensate for the defect. Thus the mutants
      of sites I and II bind to the regulatory complex but are impaired in ability to
      regulate tension and actomyosin ATPase activity, whereas the mutants of sites III
      and IV regulate activity but are unable to remain bound to thin filaments unless
      Ca2+ is present. When all four sites are intact, free Mg2+ causes a 50-60-fold
      increase in TnC's affinity for the other components of the regulatory complex,
      allowing it to attach firmly to thin filaments. Calcium can replace Mg2+ at a
      concentration ratio of 1:5000, and at this ratio the Ca2.TnC complex is more
      tightly bound to the filaments than the Mg2.TnC form. In the C-terminal mutants,
      higher concentrations of Ca2+ (above tension threshold) are required to effect
      this transformation than in the recombinant wild-type protein, suggesting that
      the mutants reveal an attachment mediated by Ca2+ in the N-domain sites.

PMID- 7730356
TI  - The propeptide is nonessential for the expression of human cathepsin D.
AB  - When the 44-amino acid propeptide of human procathepsin D was deleted by
      mutagenesis in vitro, the mature protein was stably expressed and secreted from
      transfected mammalian cells. The secreted protein was correctly folded as judged
      by its binding to pepstatinylagarose. We were unable to detect lysosomal
      targeting of the propeptide-deleted protein, and targeting was not restored by
      the substitution of the propeptides from pepsin or renin. We conclude that its
      propeptide is not essential for the folding of nascent cathepsin D. Efficient
      lysosomal targeting in mammalian cells appears to require the precursor form of
      the molecule.

PMID- 7730357
TI  - An inverted repeat motif stabilizes binding of E2F and enhances transcription of
      the dihydrofolate reductase gene.
AB  - An overlapping inverted repeat sequence that binds the eukaryotic transcription
      factor E2F is 100% conserved near the major transcription start sites in the
      promoters of three mammalian genes encoding dihydrofolate reductase, and is also
      found in the promoters of several other important cellular and viral genes. This
      element, 5'-TTTCGCGCCAAA-3', is comprised of two overlapping, oppositely oriented
      sites which match the consensus E2F site (5'-TTT(C/G)(C/G)CGC-3'). Recent work
      has shown that E2F binding activity is composed of at least six related cellular
      polypeptides which are capable of forming DNA-binding homo- and heterodimers. We
      have investigated the binding of cellular E2F activity and of homo- and
      heterodimers of cloned E2F proteins to the inverted repeat E2F element. We have
      demonstrated that mutations in this element that abolish its inverted repeat
      nature, while preserving a single consensus E2F site, significantly decrease the
      binding stability of all of the forms of E2F tested. The rate of association of
      E2F-1/DP-1 heterodimers with the inverted repeat wild type site was not
      significantly different from those with the two single site mutated probes.
      Furthermore, the mutations decrease in vitro transcription and transient reporter
      gene expression 2-5-fold, an effect equivalent to that of abolishing E2F binding
      altogether. These data suggest a functional role that may explain the
      conservation of inverted repeat E2F elements among the DHFR promoters and several
      other cellular and viral promoters.

PMID- 7730358
TI  - The requirement for molecular chaperones in lambda DNA replication is reduced by
      the mutation pi in lambda P gene, which weakens the interaction between lambda P
      protein and DnaB helicase.
AB  - During the initiation of lambda DNA replication, the host DnaB helicase is
      complexed with phage lambda P protein in order to be properly positioned near the
      ori lambda-lambda O initiation complex. However, the lambda P-DnaB interaction
      inhibits the activities of DnaB. Thus, the concerted action of bacterial heat
      shock proteins, DnaK, DnaJ, and GrpE, is required to activate the helicase. Wild
      type phage lambda cannot grow on the E. coli dnaB, dnaK, dnaJ, and grpE mutants.
      However, lambda phage with a mutation pi in the lambda P gene, is able to produce
      progeny in these mutants as well as in the wild-type bacteria. Purified mutant
      lambda pi protein reveals a much lower affinity to DnaB than wild-type lambda P,
      and the lambda pi-DnaB complex is unstable. Also, a very low concentration of
      DnaK protein is sufficient to activate the helicase in a replication system based
      on lambda dv dsDNA. In that system, the mutant DnaK756 protein, inactive in the
      lambda P-dependent replication, revealed its activity in the lambda pi-dependent
      reaction. The lambda O-lambda P-dependent replication system based on M13 ssDNA
      efficiently replicates DNA in the absence of any chaperone protein, unless lambda
      P is substituted by the lambda pi mutant protein. Data presented in this paper
      explain why lambda pi phage is able to grow on wild-type and dnaK756 bacteria.

PMID- 7730359
TI  - Cyclooxygenase-dependent formation of the isoprostane, 8-epi prostaglandin F2
      alpha.
AB  - Isoprostanes are a family of prostaglandin (PG) isomers formed in an enzyme
      independent manner. They circulate in plasma and are excreted in urine. One of
      them, 8-epi PGF2 alpha is a vasoconstrictor and mitogen, effects which are
      prevented by thromboxane antagonists. Given that 8-epi PGF2 alpha may be formed
      by cyclooxygenase (COX) (Corey, E. J., Shih, C., Shig, N-Y., and Shimoji, K.
      (1984) Tetrahedron Letts. 44, 5013-5016; Hecker, M., Ullrich, V., Fischer, C.,
      and Meese, C.O. (1987) Eur J. Biochem. 169, 113-123) and that this might confound
      its use as an index of free radical generation, we sought to characterize the
      mechanism of its formation by human platelets. Activation of platelets by
      threshold concentrations of collagen, thrombin, and arachidonic acid resulted in
      formation of 8-epi PGF2 alpha coincident with that of the COX product,
      thromboxane, and the 12 lipoxygenase product, 12-hydroxyeicosatetraenoic acid, as
      detected by selected ion monitoring assays using gas chromatography-mass
      spectrometry. The effect appeared selective for 8-epi PGF2 alpha among the F2
      isoprostanes. Pretreatment of platelets with aspirin or indomethacin abolished 8
      epi PGF2 alpha formation. COX-independent activation of platelets by high doses
      of collagen or thrombin, by the phorbol ester, phorbol 12-myristate 13-acetate,
      or the prostaglandin endoperoxide analog, U 46619 was not associated with 8-epi
      PGF2 alpha formation. Confirmation of the nature of the material formed by
      platelet COX as 8-epi PGF2 alpha included its cochromatography over three highly
      resolving high performance liquid chromatography systems, identification by
      electron impact mass spectrometry, and its formation by partially purified COX.
      Inhibition of platelet thromboxane formation was associated with augmented 8-epi
      PGF2 alpha formation. A major component of 8-epi PGF2 alpha formed in serum by
      healthy volunteers was shown to be sensitive to inhibition by aspirin ex vivo. In
      addition to its generation by free radical catalyzed mechanisms, 8-epi PGF2 alpha
      may be formed as a PG by human platelets. Given that activation of platelet COX
      characterizes many of the human syndromes which are putatively associated with
      free radical generation, assessment of the contribution of this pathway is
      relevant to the use of 8-epi PGF2 alpha as an index of lipid peroxidation in
      vivo.

PMID- 7730360
TI  - Two distinct Raf domains mediate interaction with Ras.
AB  - A key event for Ras transformation involves the direct physical association
      between Ras and the Raf-1 kinase. This interaction promotes both Raf
      translocation to the plasma membrane and activation of Raf kinase activity.
      Although substantial experimental evidence has demonstrated that Raf residues 51
      131 alone are sufficient for Ras binding, conflicting observations have suggested
      that the Raf cysteine-rich domain (residues 139-184) may also be important for
      interaction with Ras. To clarify the role of the Raf cysteine-rich domain in Ras
      Raf binding, we have compared the ability of two distinct Raf fragments to
      interact with Ras using both in vitro Ras binding and in vivo Ras inhibition
      assays. First, we determined that both Raf sequences 2-140 and 139-186
      (designated Raf-Cys) showed preferential binding to active, GTP-bound Ras in
      vitro. Second, we observed that Raf-Cys antagonized oncogenic Ras(Q61L)-mediated
      transactivation of Ras-responsive elements and focus-forming activity in NIH 3T3
      cells and insulin-induced germinal vesicle breakdown in Xenopus laevis oocytes in
      vivo. This inhibitory activity suggests that Raf-Cys can interact with Ras in
      vivo. Taken together, these results suggest that Ras interaction with two
      distinct domains of Raf-1 may be important in Ras-mediated activation of Raf
      kinase activity.

PMID- 7730361
TI  - Role of the Chlamydomonas reinhardtii coupling factor 1 gamma-subunit cysteine
      bridge in the regulation of ATP synthase.
AB  - The gamma-subunit of coupling factor 1 (CF1) contains a cysteine bridge that is
      thought to be involved in the redox control of enzymatic activity. In order to
      test the regulatory significance of this disulfide bond, genetic transformation
      experiments with Chlamydomonas reinhardtii were performed. C. reinhardtii strain
      atpC1 (nit1-305, cw 15, mt-), which is null for the gamma-subunit, was
      transformed and complemented with gamma-subunit constructs containing amino acid
      substitutions localized to the cysteine bridge between Cys198 and Cys204.
      Successful complementation was confirmed by phenotypic selection, Northern blot
      analysis, reverse transcription polymerase chain reaction, and cDNA sequencing.
      CF1 ATPase activities of the soluble enzymes were measured in the presence and
      absence of dithiothreitol (DTT). Mutant CF1 enzymes showed no effect of DTT
      although increased activity was observed for the wild-type enzyme. In vitro,
      phenazine methosulfate-dependent photophosphorylation assays revealed that wild
      type CF1 exhibits a 2-fold stimulation in the presence of 25 mM DTT, whereas each
      of the mutant enzymes has activities that are DTT-independent. Growth
      measurements indicated that despite the absence of a regulatory
      disulfide/dithiol, the mutant strains grew with the same kinetics as wild type.
      This study provides evidence to illustrate the involvement of the gamma-subunit
      in the redox regulation of ATP synthesis in vivo. This work is also the first
      demonstration in C. reinhardtii of stable nuclear transformation using mutated
      genes to complement a known defect.

PMID- 7730362
TI  - Proline dehydrogenase activity of the transcriptional repressor PutA is required
      for induction of the put operon by proline.
AB  - The proline utilization (put) operon from Salmonella typhimurium consists of the
      putP gene, encoding a proline transporter, and the putA gene, encoding an enzyme
      with both proline dehydrogenase and 1-pyrroline-5-carboxylate dehydrogenase
      activities. In addition to these two enzymatic activities, the PutA protein is a
      transcriptional repressor that regulates the expression of putP and putA in
      response to the availability of proline. We report the isolation of super
      repressor mutants of PutA that decrease expression from the putA promoter in the
      presence or absence of proline. None of the mutants exhibited increased affinity
      for the DNA in the put regulatory region in vitro. Although DNA binding by wild
      type PutA was prevented by the addition of proline and an artificial electron
      acceptor, DNA binding by the two strongest super-repressors was not prevented
      under identical conditions. The proline dehydrogenase activity of the purified
      mutant proteins showed altered kinetic properties (increased Km(Pro), reduced
      Vmax, or a completely null phenotype). The observation that these mutations
      simultaneously affect induction by proline and proline dehydrogenase activity
      suggests that a single proline-binding site is involved in both proline
      dehydrogenase activity and induction of the expression of the put operon.
      Furthermore, the results indicate that the proline dehydrogenase activity of PutA
      is essential for induction of the put operon by proline.

PMID- 7730363
TI  - Different alpha 1-adrenergic receptor sequences required for activating different
      G alpha subunits of Gq class of G proteins.
AB  - In order to understand the specific interactions between receptors and guanine
      nucleotide-binding regulatory protein (G proteins), we attempted to delineate the
      alpha 1 B-adrenergic receptor sequences involved in activation of the alpha
      subunits of the Gq class of G proteins. A number of specific mutations were
      introduced into the third inner loop of the receptor, and the mutants were tested
      for their abilities to activate different G alpha subunits of the Gq class. Our
      results indicate that the receptor sequences required for activating G alpha
      q/11, G alpha 14, or G alpha 16 are different. The sequence extending from
      residues Lys240 to His252 is required for activation of G alpha q/11, but not for
      activation of G alpha 14 or G alpha 16. Two segments in the third loop of the
      receptor are required for activation of G alpha 14: one is located at the N
      terminus of the loop ending at residue Asn226, and the other is located at the C
      terminus of the loop starting from residue Ser278. The latter contains a BBXXB
      motif, which is apparently critical for G alpha 14 coupling, but not for G alpha
      16 or G alpha q/11 coupling. Furthermore, the three amino acids stretch (Tyr217
      to Val219) included in the N-terminal segment is not only required for G alpha 14
      coupling, but also for G alpha q/11 coupling. It may be involved to some extent
      in G alpha 16 coupling as well.

PMID- 7730364
TI  - Analysis of the role of protein kinase C-alpha, -epsilon, and -zeta in T cell
      activation.
AB  - T cells express multiple isotypes of protein kinase C (PKC) and although it is
      well accepted that PKCs have an important role in T cell activation, little is
      known about the function of individual PKC isotypes. To address this issue,
      mutationally active PKC-alpha, -epsilon, or -zeta have been transfected into T
      cells and the consequences for T cell activation determined. p21ras plays an
      essential role in T cell activation. Accordingly, the effects of the
      constitutively active PKCs were compared to the effects of mutationally activated
      p21ras. The data indicate that PKC-epsilon and, to a lesser extent PKC-alpha but
      not -zeta, can regulate the transcription factors AP-1 and nuclear factor of
      activated T cells (NF-AT-1). The ability of PKC-epsilon to induce transactivation
      of NF-AT-1 and AP-1 was similar to the stimulatory effect of a constitutively
      activated p21ras. PKC-epsilon, but not PKC-alpha nor activated p21ras, was able
      to induce NF-KB activity. Phorbol esters induce expression of CD69 whereas none
      of the activated PKC isotypes tested were able to have this effect. Activated Src
      and p21ras were able to induce CD69 expression. These results indicate selective
      functions for different PKC isotypes in T cells. Moreover, the data comparing the
      effects of activated Ras and PKC mutants suggest that PKC-alpha, p21ras, and PKC
      epsilon are not positioned linearly on a single signal transduction pathway.

PMID- 7730365
TI  - Sequence requirements for binding of Src family tyrosine kinases to activated
      growth factor receptors.
AB  - Activation of growth factor receptor protein tyrosine kinases frequently results
      in the binding of numerous proteins to their tyrosine-phosphorylated cytoplasmic
      domains. These interactions involve the SH2 domains of the binding proteins and
      phosphorylated tyrosines on the receptor molecules, with the specificity of
      interaction dictated by the amino acid composition surrounding the phosphorylated
      tyrosine. In the case of the platelet-derived growth factor (PDGF) receptor, the
      major binding site for Src family tyrosine kinases is in the juxtamembrane domain
      and includes tyrosine 579 (Mori, S., Ronnstrand, L., Yokote, K., Engstrom, A.,
      Courtneidge, S. A., Claesson-Welsh, L., and Heldin, C-H. (1993) EMBO J. 12, 2257
      2264). To analyze in more detail which amino acids surrounding the phosphorylated
      tyrosine at position 579 were important for high affinity interaction with Src
      family kinases, we synthesized a series of phosphopeptides corresponding to this
      binding site in which single amino acids were individually changed and tested
      their ability to compete with the PDGF receptor for binding of Fyn. We found that
      not only the three residues carboxyl-terminal to the phosphorylated tyrosine were
      important but that also residues at positions -1 and +4 relative to the tyrosine
      were required. Phosphorylation of both tyrosines 579 and 581 significantly
      increased competition efficiency. The activated colony stimulating factor-1 (CSF
      1) receptor, which is known to associate with Src family kinases, has a sequence
      in its juxtamembrane region similar to that surrounding Tyr-579 of the PDGF
      receptor, and a phosphopeptide modeled on this sequence competed the association
      of Fyn with the receptor in vitro. Furthermore, mutational analysis demonstrated
      that these sequences were required for the efficient association of Src family
      kinases with the activated CSF-1 receptor in vivo. Phosphopeptides corresponding
      to the Src family binding sites of both PDGF and CSF-1 receptors activated Src
      kinase activity in vitro. These observations support a model in which the
      enzymatic activity of Src family tyrosine kinases is controlled by intra- and
      intermolecular interactions of tyrosine-phosphorylated peptides with the SH2
      domain of the kinases.

PMID- 7730366
TI  - Affinity purification and cDNA cloning of rat neural differentiation and tumor
      cell surface antigen gp130RB13-6 reveals relationship to human and murine PC-1.
AB  - Monoclonal antibody RB13-6 recognizes a subset of rat brain glial precursor cells
      that are highly susceptible to malignant conversion by the carcinogen N-ethyl-N
      nitrosourea. The corresponding cell surface antigen was identified as a membrane
      glycoprotein (gp130RB13-6) and purified by immunoaffinity chromatography from the
      tumorigenic neuroectodermal rat cell line BT4Ca. Sequencing of 5 endoproteinase
      generated peptides of the purified antigen permitted the specific amplification
      of a cDNA fragment by reverse transcription-polymerase chain reaction and
      subsequent isolation of the complete coding sequence from a fetal rat brain cDNA
      library. The derived amino acid sequence indicates that the RB13-6 antigen is
      related to the human and murine plasma cell membrane protein PC-1, a nucleotide
      pyrophosphatase/alkaline phosphodiesterase and ectoprotein kinase. Similarly,
      purified gp130RB13-6 possesses 5'-nucleotidase activity that can be inhibited
      with EDTA. Different from PC-1, gp130RB13-6 isolated from BT4Ca cells is not a
      disulfide-linked dimer and contains an RGD-tripeptide sequence which, together
      with other structural features, suggests a possible function in cell adhesion and
      its subversion in malignant phenotypes.

PMID- 7730367
TI  - Localization of I2-imidazoline binding sites on monoamine oxidases.
AB  - Imidazoline binding sites (IBS) were proposed to be responsible for some of the
      pharmacological and therapeutic activities of imidazoline and related compounds
      and have been classified into two subtypes, I1BS and I2BS. Convergent studies
      attribute a role in central blood pressure regulation to the I1BS. In contrast,
      the function of I2BS remains unknown. In the present study, by combining
      biochemical and molecular biology approaches, we show that 1) microsequencing of
      I2BS purified from rabbit kidney mitochondria allowed the recovery of four
      peptide sequence stretches displaying up to 85.7% similarity with human, rat, and
      bovine monoamine oxidases (MAO)-A and -B; 2) I2BS and MAO displayed identical
      biophysical characteristics as their activities, measured by [3H]idazoxan binding
      and [14C]tyramine oxidation, respectively, could not be separated using various
      chromatographic procedures; and 3) heterologous expression of human placenta MAO
      A and human liver MAO-B in yeast, inherently devoid of I2BS and MAO activities,
      led to the coexpression of [3H]idazoxan binding sites displaying ligand
      recognition properties typical of I2BS. These results show definitely that I2BS
      is located on both MAO-A and -B. The fact that I2BS ligands inhibited MAO
      activity independently of the interaction with the catalytic region suggests that
      I2BS might be a previously unknown MAO regulatory site.

PMID- 7730368
TI  - Streptococcal cysteine proteinase releases biologically active fragments of
      streptococcal surface proteins.
AB  - Streptococcus pyogenes are important pathogenic bacteria which produce an
      extracellular cysteine proteinase contributing to their virulence and
      pathogenicity. S. pyogenes also express surface molecules, M proteins, that are
      major virulence determinants due to their antiphagocytic property. In the present
      work live S. pyogenes bacteria of the M1 serotype were incubated with purified
      cysteine proteinase. Several peptides were solubilized, and analysis of their
      protein-binding properties and amino acid sequences revealed two internal
      fibrinogen-binding fragments of M1 protein (17 and 21 kDa, respectively), and a
      36-kDa IgG-binding NH2-terminal fragment of protein H, an IgGFc-binding surface
      molecule. M protein also plays a role in streptococcal adherence, and removal of
      this and other surface proteins could promote bacterial dissemination, whereas
      the generation of soluble complexes between immunoglobulins and immunoglobulin
      binding streptococcal surface proteins could be an etiological factor in the
      development of glomerulonephritis and rheumatic fever. Thus, in these serious
      complications to S. pyogenes infections immune complexes are found in affected
      organs. The cysteine proteinase also solubilized a 116-kDa internal fragment of
      C5a peptidase, another streptococcal surface protein. Activation of the
      complement system generates C5a, a peptide stimulating leukocyte chemotaxis. C5a
      mediated granulocyte migration was blocked by the 116-kDa fragment. This
      mechanism, by which phagocytes could be prevented from reaching the site of
      infection, may also contribute to the pathogenicity and virulence of S. pyogenes.

PMID- 7730369
TI  - Regulation of thrombin receptors on human umbilical vein endothelial cells.
AB  - Activated thrombin receptors on human umbilical vein endothelial cells rapidly
      undergo homologous desensitization, leaving the cells unable to respond to
      thrombin. The present studies examine the fate of activated thrombin receptors on
      endothelial cells and the mechanisms that restore intact receptors to the cell
      surface. The results show that: 1) at biologically relevant concentrations,
      thrombin rapidly cleaves all of its receptors on the cell surface. 2) The cleaved
      receptors are cleared from the cell surface in a two-phase process, with 60%
      being internalized within 10 min, the remainder requiring several hours. 3) The
      restoration of intact, thrombin-responsive receptors on the cell surface
      initially occurs from an intracellular pool of receptors in a process that is
      independent of protein synthesis. 4) Recycling of cleaved receptors either does
      not occur on endothelial cells or is masked by receptor clearance. 5)
      Subconfluent endothelial cells re-express intact receptors on the cell surface at
      a slower rate than confluent cells. 6) The agonist peptide, SFLLRN, also causes
      receptor internalization, although at concentrations greater than those required
      for receptor activation and desensitization. These results are distinctly
      different from those observed with megakaryoblastic cell lines, where > 90% of
      the activated thrombin receptors are internalized rapidly, up to 40% of the
      cleaved receptors are recycled, and no intracellular pool of intact receptors has
      been detected. Since the primary structure of the thrombin receptor is the same
      in all the cell types studied, these results demonstrate that there can be
      substantial differences between cell types in the mechanisms involved in the
      clearance of activated receptors and the re-expression on the cell surface of
      intact receptors capable of responding to thrombin.

PMID- 7730370
TI  - Identification of cytosolic proteins that bind to the Fanconi anemia
      complementation group C polypeptide in vitro. Evidence for a multimeric complex.
AB  - The oligomeric structure of Fanconi anemia complementation group C (FACC) was
      investigated in mammalian cell lysates. Using an affinity-purified polyclonal
      antibody, FACC was immunoprecipitated from radiolabeled cell lysates and shown to
      form monomers of 63 kDa. Association of FACC with heterologous proteins was
      investigated by co-precipitation of radiolabeled proteins with a recombinant
      chimeric FACC molecule fused to the constant portion of the human IgG1 heavy
      chain (FACC gamma 1). Expression of FACC gamma 1 in FACC-deficient Fanconi anemia
      (FA) lymphoblasts corrected the hypersensitivity of these cells to mitomycin C.
      Binding of FACC gamma 1 to protein A-agarose and incubation with radiolabeled
      cell lysates identified three polypeptides with molecular masses of 65, 50, and
      35 kDa that were also detected on immunoblots probed with the purified FACC gamma
      1 polypeptide. FACC, as well as the three FACC-binding polypeptides, co
      fractionated with cytosolic and membrane extracts. Binding was specific for the
      FACC moiety of FACC gamma 1 and was detected in cytosolic extracts of a number of
      FA and non-FA mammalian cells. These results demonstrate that FACC binds directly
      to a family of ubiquitous cytosolic proteins and is conserved in a wide range of
      mammalian cells.

PMID- 7730371
TI  - Hyperosmolality inhibits bicarbonate absorption in rat medullary thick ascending
      limb via a protein-tyrosine kinase-dependent pathway.
AB  - In the rat medullary thick ascending limb (MTAL), hyperosmolality inhibits
      transepithelial HCO3- absorption (JHCO3-) by inhibiting apical membrane Na+/H+
      exchange. To examine signaling mechanisms involved in this regulatory response,
      MTALs were isolated and perfused in vitro with 25 mM HCO3- solutions (290
      mosmol/kg H2O). Osmolality was increased in lumen and bath solutions by addition
      of 300 mM mannitol or 75 mM NaCl. Addition of mannitol reduced JHCO3- by 60% and
      addition of NaCl reduced JHCO3- by 50%. With the protein tyrosine kinase (PTK)
      inhibitor genistein (7 microM) or herbimycin A (1 microM) in the bath, addition
      of mannitol reduced JHCO3- only by 11% and addition of NaCl reduced JHCO3- only
      by 15%. Staurosporine (10(-7) M) or forskolin (10(-6) M) in the bath had no
      effect on inhibition of JHCO3- by hypertonic NaCl. Genistein had no effect on
      inhibition of JHCO3- by vasopressin (a cyclic AMP-dependent process) or
      stimulation of JHCO3- by prostaglandin E2 (a protein kinase C-dependent process).
      Under isosmotic conditions, addition of genistein or herbimycin A to the bath
      increased JHCO3- by 30% through stimulation of apical membrane Na+/H+ exchange.
      Addition of the tyrosine phosphatase inhibitor molybdate (50 microM) to the bath
      reproduced the inhibition of JHCO3- observed with hyperosmolality. These data
      indicate that 1) the effect of hyperosmolality to inhibit MTAL HCO3- absorption
      through inhibition of apical membrane Na+/H+ exchange is mediated via a PTK
      dependent pathway that functions independent of regulation by cyclic AMP and
      protein kinase C, and 2) a constitutive PTK activity inhibits apical membrane
      Na+/H+ exchange and HCO3- absorption under isosmotic conditions. Our results
      suggest that tyrosine phosphorylation is a critical step in inhibition of the
      apical Na+/H+ exchanger isoform NHE-3 by hyperosmolality.

PMID- 7730372
TI  - Arachidonic acid inhibits a purified and reconstituted glutamate transporter
      directly from the water phase and not via the phospholipid membrane.
AB  - Glutamate is believed to be the major excitatory transmitter in the mammalian
      central nervous system. Keeping the extracellular concentration of glutamate low,
      the glutamate transporters are required for normal brain function. Arachidonic
      acid (AA) inhibits glutamate uptake in relatively intact preparations (cells,
      tissue slices, and synaptosomes (Rhoads, D.E., Ockner, R. K., Peterson, N. A.,
      and Raghupathy, E. (1983) Biochemistry 22, 1965-1970 and Volterra, A., Trotti,
      D., Cassutti, P., Tromba, C., Salvaggio, A., Melcangi, R. C., and Racagni, G.
      (1992b) J. Neurochem. 59, 600-606). The present study demonstrates that the
      effect of AA occurs also in a reconstituted system, consisting of a purified
      glutamate transporter protein incorporated into artificial cell membranes
      (liposomes). The characteristics of the AA effect in this system and in intact
      cells are similar with regard to specificity, sensitivity, time course, changes
      in Vmax, and affinity. AA-ethyl ester is inactive, suggesting that the free
      carboxylic group is required for inhibitory activity. When incubated with
      proteoliposomes, AA (300 microM, 15 min) mostly partitions to the lipid phase
      (lipid/water about 95:5). However, uptake inhibition is abolished by rapid
      dilution (6.5-fold) of the incubation medium (water phase), a procedure that does
      not modify the amount of AA associated with lipids. On the contrary, inhibition
      remains sustained if the same dilution volume contains as little as 5 microM AA,
      a concentration inactive before saturation of liposome lipids with 300 microM AA.
      The same degree of inhibition (60%) is obtained by 5 microM AA following
      preincubation with the inactive AA-ethyl ester (300 microM) instead of AA. The
      lipids apparently inactivate AA by extracting it from the water phase. The
      results suggest that AA acts on the transporter from the water phase rather than
      via the membrane. This could be true for other proteins as well since gamma
      aminobutyric acid uptake is similarly affected by AA.

PMID- 7730373
TI  - Transfected aequorin in the measurement of cytosolic Ca2+ concentration
      ([Ca2+]c). A critical evaluation.
AB  - Targeted recombinant aequorins represent to date the most specific means of
      monitoring [Ca2+] in subcellular organelles (Rizzuto, R., Simpson, A. W. M.,
      Brini, M., and Pozzan, T. (1992) Nature 358, 325-328; Brini, M., Murgia, M.,
      Pasti, L., Picard, D., Pozzan, T., and Rizzuto, R. (1993) EMBO J. 12, 4813-4819;
      Kendall, J. M., Dormer, R. L., and Campbell, A. K. (1992) Biochem. Biophys. Res.
      Commun. 189, 1008-1016). Up until now, however, only limited attention has been
      paid to the use of recombinant photoproteins for measuring, in mammalian cells,
      the [Ca2+] in the cytoplasm, a compartment for which effective Ca2+ probes are
      already available. Here we describe this approach in detail, highlighting the
      advantages, under various experimental conditions, of using recombinant cytosolic
      aequorin (cytAEQ) instead of classical fluorescent indicators. We demonstrate
      that cytAEQ is expressed recombinantly at high levels in transiently transfected
      cell lines and primary cultures as well as in stably transfected clones, and we
      describe a simple algorithm for converting aequorin luminescence data into [Ca2+]
      values. We show that although fluorescent indicators at the usual intracellular
      concentrations (50-100 microM) are associated with a significant buffering of the
      [Ca2+]c transients, this problem is negligible with recombinantly expressed
      aequorin. The large dynamic range of the photoprotein also allows an accurate
      estimate of the large [Ca2+]c increases that are observed in some cell types such
      as neurons. Finally, cytAEQ appears to be an invaluable tool for measuring
      [Ca2+]c in cotransfection experiments. In particular, we show that when
      cotransfected with an alpha 1-adrenergic receptor (coupled to inositol 1,4,5
      trisphosphate generation), cytAEQ faithfully monitors the subpopulation of cells
      expressing the receptor, whereas the signal of fura-2, at the population level,
      is dominated largely by that of the untransfected cells.

PMID- 7730374
TI  - Kinetics of binding of caldesmon to actin.
AB  - The time course of interaction of caldesmon with actin may be monitored by
      fluorescence changes that occur upon the binding of 12-(N-methyl-N-(7-nitrobenz-2
      oxa-1,3-diazol-4-yl))-labeled caldesmon to actin or to acrylodan actin. The
      concentration dependence of the observed rate of caldesmon-actin binding was
      analyzed to a first approximation as a single-step reaction using a Monte Carlo
      simulation. The derived association and dissociation rates were 10(7) M-1 s-1 and
      18.2 s-1, respectively. Smooth muscle tropomyosin enhances the binding of
      caldesmon to actin, and this was found to be due to a reduction in the rate of
      dissociation to 6.3 s-1. There is no evidence from this study for a different
      mechanism of binding in the presence of tropomyosin. The fluorescence changes
      that occurred with the binding of 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl))-labeled caldesmon to actin or actin-tropomyosin were reversed by the
      addition of myosin subfragment 1 as predicted by a competitive binding mechanism.

PMID- 7730375
TI  - Site-directed mutagenesis of the alpha subunit of human prolyl 4-hydroxylase.
      Identification of three histidine residues critical for catalytic activity.
AB  - Prolyl 4-hydroxylase (EC 1.14.11.2) catalyzes the formation of 4-hydroxyproline
      in collagens. The vertebrate enzyme is an alpha 2 beta 2 tetramer in which the
      alpha subunits contribute to most parts of the two catalytic sites. To study the
      roles of histidine and cysteine residues in this catalytic activity we converted
      all 5 histidines that are conserved between species, 4 nonconserved histidines,
      and 3 conserved cysteines of the human alpha subunit individually to serine and
      expressed the mutant alpha subunits together with the wild-type beta subunit in
      insect cells by means of baculovirus vectors. Mutation of any of the 3 conserved
      histidines, residues 412, 483, and 501, inactivated the enzyme completely or
      essentially completely, with no effect on tetramer assembly or binding of the
      tetramer to poly(L-proline). These histidines are likely to provide the three
      ligands needed for the binding of Fe2+ to a catalytic site. Mutation of either of
      the other 2 conserved histidines reduced the amount of enzyme tetramer by 20-25%
      and the activity of the tetramer by 30-60%. Mutation of the nonconserved
      histidine 324 totally prevented tetramer assembly, whereas mutation of the 3
      other nonconserved histidines had no effects. Two of the 3 cysteine to serine
      mutations, those involving residues 486 and 511, totally prevented tetramer
      assembly under the present conditions, whereas the third, involving residue 150,
      had only a minor effect in reducing tetramer assembly and activity. The data do
      not support previous suggestions that cysteine residues are involved in Fe2+
      binding sites. Additional mutagenesis experiments demonstrated that the two
      glycosylated asparagines have no role in tetramer assembly or catalytic activity.

PMID- 7730376
TI  - A new polyamine 4-aminobutylcadaverine. Occurrence and its biosynthesis in root
      nodules of adzuki bean plant Vigna angularis.
AB  - Root nodules of adzuki bean plant (Vigna angularis) contained a novel polyamine.
      The chemical structure of the new polyamine was determined to be NH2(CH2)5
      NH(CH2)4NH2 (4-aminobutylcadaverine) based on gas chromatography-mass
      spectrometry. The occurrence of 4-aminobutylcadaverine was specific to the root
      nodules, since the unusual triamine was not detected in other organs of the
      adzuki bean plant. Bacteroids, isolated from root nodules, contained both sym
      homospermidine and 4-aminobutylcadaverine, whereas the plant cytosol fraction
      contained large quantities of putrescine and cadaverine. A cell-free extract of
      bacteroids showed the ability to form this triamine from putrescine and
      cadaverine under the presence of NAD+ and K+. 1,3-Diaminopropane and NADH were
      inhibitory for the synthesis of both sym-homospermidine and 4
      aminobutylcadaverine. [1,4-15N]Putrescine was incorporated not only into sym
      homospermidine but also into 4-aminobutylcadaverine by the cell-free extract of
      bacteroids when incubated with excess cadaverine. Analysis of the fragment ion
      peaks in the 15N-enriched 4-aminobutylcadaverine indicated the transfer of a
      aminobutyl moiety to the amino terminus of cadaverine. These results suggest
      that, in adzuki bean, 4-aminobutylcadaverine is formed through the action of
      homospermidine synthase in nodule bacteroids under a cadaverine-rich environment.

PMID- 7730377
TI  - Human beta-cell glucokinase. Dual role of Ser-151 in catalysis and hexose
      affinity.
AB  - Glucokinase is distinguished from yeast hexokinase and low Km mammalian
      hexokinases by its low affinity for glucose and its cooperative behavior, even
      though glucose binding residues and catalytic residues are highly conserved in
      all of these forms of hexokinase. The roles of Ser-151 and Asn-166 as
      determinants of hexose affinity and cooperative behavior of human glucokinase
      have been evaluated by site-directed mutagenesis, expression and purification of
      the wild-type and mutant enzymes, and steady-state kinetic analysis. Mutation of
      Asn-166 to arginine increased apparent affinity for both glucose and ATP by a
      factor of 3. Mutation of Ser-151 to cysteine, alanine, or glycine lowered the Km
      for glucose by factors of 2-, 26-, and 40-fold, respectively, decreased Vmax,
      abolished cooperativity for glucose, and also decreased Km for mannose and
      fructose. The Ser-151 mutants had hexose Km values similar to those of yeast
      hexokinase, hexokinase I, and the recombinantly expressed COOH-terminal half of
      hexokinase I. However, the Ki values for the competitive inhibitors, N
      acetylglucosamine and glucose-6-P, were unchanged, suggesting that Ser-151 is not
      important for inhibitor binding. Mutation of Ser-151 also increased the Km for
      ATP about 5-fold and abolished the enzyme's low ATPase activity, which indicates
      it is essential for ATP hydrolysis. The substrate-induced change in intrinsic
      fluorescence of S151A occurred at a much lower glucose concentration than that
      for wild-type enzyme. The results implicate a dual role for Ser-151 as a
      determinant of hexose affinity and catalysis, exclusive of the glucose-induced
      conformational change, and suggest that the low hexose affinity of glucokinase is
      dependent on interaction of Ser-151 with other regions of the protein.

PMID- 7730378
TI  - Structural analysis of saposin C and B. Complete localization of disulfide
      bridges.
AB  - Saposins A, B, C, and D are a group of homologous glycoproteins derived from a
      single precursor, prosaposin, and apparently involved in the stimulation of the
      enzymatic degradation of sphingolipids in lysosomes. All saposins have six
      cysteine residues at similar positions. In the present study we have investigated
      the disulfide structure of saposins B and C using advanced mass spectrometric
      procedures. Electrospray analysis showed that deglycosylated saposins B and C are
      mainly present as 79- and 80-residue monomeric polypeptides, respectively. Fast
      atom bombardment mass analysis of peptide mixtures obtained by a combination of
      chemical and enzymatic cleavages demonstrated that the pairings of the three
      disulfide bridges present in each saposin are Cys4-Cys77, Cys7-Cys71, Cys36-Cys47
      for saposin B and Cys5-Cys78, Cys8-Cys72, Cys36-Cys47 for saposin C. We have
      recently shown that saposin C interacts with phosphatidylserine-containing
      vesicles inducing destabilization of the lipid surface (Vaccaro, A. M., Tatti,
      M., Ciaffoni, F., Salvioli, R., Serafino, A., and Barca, A. (1994) FEBS Lett.
      349, 181-186); this perturbation promotes the binding of the lysosomal enzyme
      glucosylceramidase to the vesicles and the reconstitution of its activity. It was
      presently found that the effects of saposin C on phosphatidylserine liposomes and
      on glucosylceramidase activity are markedly reduced when the three disulfide
      bonds are irreversibly disrupted. These results stress the importance of the
      disulfide structure for the functional properties of the saposin.

PMID- 7730379
TI  - QSR1, an essential yeast gene with a genetic relationship to a subunit of the
      mitochondrial cytochrome bc1 complex, is homologous to a gene implicated in
      eukaryotic cell differentiation.
AB  - Subunit 6 of the mitochondrial cytochrome bc1 complex regulates the activity of
      the bc1 complex in Saccharomyces cerevisiae but is not essential for respiration.
      To test whether QCR6, the nuclear gene which encodes subunit 6, might be
      functionally redundant with any other gene(s), we screened for mutations in yeast
      genes which are essential when the otherwise non-essential QCR6 is deleted from
      the yeast chromosome. We obtained such quinolcytochrome c reductase subunit
      requiring mutants in two complementation groups, which we named qsr1 and qsr2.
      The qsr mutants require QCR6 for viability on fermentable and non-fermentable
      carbon sources, indicating that QCR6 is covering lethal mutations in qsr1 and
      qsr2, even when the yeast do not require respiration. QSR1 was cloned by rescuing
      the synthetic lethality of a qsr1-1 mutant. QSR1 encodes a 25.4-kDa protein which
      is 65% identical to a protein encoded by QM, a highly conserved human gene which
      has been implicated in tumorigenesis. In mammals QM is down-regulated during
      adipocyte, kidney, and heart differentiation, and in Nicotiana the homolog of QM
      is also down-regulated during differentiation. When one chromosomal copy of QSR1
      was deleted in a diploid yeast strain, haploid spores derived therefrom and
      carrying the deletion were unable to grow on fermentable or non-fermentable
      carbon sources. Although QCR6 allows the qsr1-1 mutant to grow, it will not
      substitute for QSR1, since the deletion of QSR1 is lethal even if QCR6 is
      present. These results indicate a novel genetic relationship between a subunit of
      the mitochondrial respiratory chain and an essential gene in yeast which is
      homologous to a gene implicated in differentiation in other eukaryotes.

PMID- 7730380
TI  - Growth and differentiation proceeds normally in cells deficient in the immediate
      early gene NGFI-A.
AB  - NGFI-A (also known as EGR-1, zif/268, and Krox-24) is a zinc finger transcription
      factor induced in many cell types by a variety of growth and differentiation
      stimuli. To determine if NGFI-A plays a requisite role in these processes, we
      used homologous recombination to mutate both alleles of NGFI-A in embryonic stem
      (ES) cells and examined its effect on growth and differentiation. We find that ES
      cells lacking NGFI-A exhibit similar growth rates and serum-induced gene
      expression profiles compared to wild-type parental cells. They are capable of
      differentiating into neurons, cardiac myocytes, chondrocytes, and squamous
      epithelium. Chimeric mice were generated from targeted ES cells, and their
      progeny were crossed to produce homozygous mutant mice. Growth and histological
      analyses of mice lacking NGFI-A confirm the finding in ES cells that NGFI-A is
      not required for many of the processes associated with its expression and suggest
      that the function of NGFI-A is either more subtle in vivo or masked by redundant
      expression provided by other gene family members such as NGFI-C, Krox-20, or
      EGR3.

PMID- 7730381
TI  - Sugar recognition by a glucose/galactose receptor. Evaluation of binding
      energetics from molecular dynamics simulations.
AB  - A new theoretical method for free energy calculations is used to compute the
      absolute binding constants for beta-D-glucose and methyl-beta-D-galactoside to
      the periplasmic glucose/galactose receptor from Salmonella typhimurium. The
      computer simulation results agree well with available experimental data and make
      it possible to assess the sources of both the high affinity as well as the
      specificity for glucose. It was found that the major contribution to the binding
      energy comes from electrostatic interactions and particularly hydrogen bonds of
      the charge-dipole type. We also predict the structure of the complex with methyl
      galactoside as this has not yet been experimentally determined.

PMID- 7730382
TI  - Neu differentiation factor inhibits EGF binding. A model for trans-regulation
      within the ErbB family of receptor tyrosine kinases.
AB  - Neu differentiation factor (NDF, or heregulin) and epidermal growth factor (EGF)
      are structurally related proteins that bind to distinct members of the ErbB
      family of receptor tyrosine kinases. Here we show that NDF inhibits EGF binding
      in a cell type-specific manner. The inhibitory effect is distinct from previously
      characterized mechanisms that involve protein kinase C and receptor
      internalization because it occurred at 4 degrees C and displayed reversibility.
      The extent of inhibition correlated with both receptor saturation and affinity of
      different NDF isoforms, and it was abolished upon overexpression of either EGF
      receptor or ErbB-2. Binding kinetics and equilibrium analyses indicated that NDF
      reduced the affinity, rather than the number, of EGF receptors, through an
      acceleration of the rate of ligand dissociation and deceleration of the
      association rate. On the basis of co-immunoprecipitation of EGF and NDF
      receptors, we attribute the inhibitory effect to the formation of receptor
      heterodimers. According to this model, EGF binding to NDF-occupied heterodimers
      is partially blocked. This model of negative trans-regulation within the ErbB
      family is relevant to other subgroups of receptor tyrosine kinases and may have
      physiological implications.

PMID- 7730383
TI  - Immunocytochemical localization of eight protein kinase C isozymes overexpressed
      in NIH 3T3 fibroblasts. Isoform-specific association with microfilaments, Golgi,
      endoplasmic reticulum, and nuclear and cell membranes.
AB  - We have used immunocytochemical analyses to characterize the subcellular
      distribution of protein kinase C (PKC)-alpha, -beta I, -beta II, -gamma, -delta, 
      epsilon, -zeta, and -eta in NIH 3T3 fibroblasts that overexpress these different
      PKC isozymes. Immunofluorescence studies and Western blotting with antibodies
      specific for individual isoforms revealed that before activation the majority of
      the PKCs are not membrane-bound and are diffusely distributed throughout the
      cytoplasm. In addition, a fraction of PKC-delta and -eta appears membrane-bound
      and concentrated in the Golgi apparatus. Activation of each isozyme's kinase
      activity (with the exception of PKC-zeta) by treatment of these cells with the
      phorbol ester 12-O-tetradecanoylphorbol-13-acetate results in isozyme-specific
      alterations of cell morphology, as well as in a rapid, selective redistribution
      of the different PKC isozymes to distinct subcellular structures. Within minutes
      after 12-O-tetradecanoylphorbol-13-acetate treatment, PKC-alpha and -epsilon
      concentrate at cell margins. In addition, PKC-alpha accumulates in the
      endoplasmic reticulum, PKC-beta II associates with actin-rich microfilaments of
      the cytoskeleton, PKC-gamma accumulates in Golgi organelles, and PKC-epsilon
      associates with nuclear membranes. Our results demonstrate that each activated
      PKC isozyme specifically associates with a particular cellular structure,
      presumably containing the substrate for that isozyme. These findings support the
      hypothesis that PKC substrate specificity in vivo is mediated, at least in part,
      by the restricted subcellular locale for each PKC isozyme and its target protein.

PMID- 7730384
TI  - A two-dimensional kinematic model of the lumbrical in the human finger.
AB  - The functioning of the lumbrical muscle in the human finger is difficult to
      visualise. This is mainly due to the fact that the origin and insertion of the
      lumbrical is on tendons of other motors (the deep flexor and the extensor
      assembly, respectively), instead of on bone. In this paper the functioning of the
      lumbrical in the human finger is kinematically investigated by explicitly
      considering the slackness or tautness of tendon parts which are in parallel or in
      series with the lumbrical, and by deriving from a standard finger model
      equivalent representations from which the functioning of the lumbrical is
      visually more clear. These models are used to review and interpret the results of
      previous studies. Further, it is indicated that the lumbrical is in an ideal
      position to contribute to the control of certain fast movements, as may be of
      importance for the musician, and that its role in other fast movements may be
      limited because of its large displacements (contraction speed).

PMID- 7730385
TI  - The redundant nature of locomotor optimization laws.
AB  - A sagittal-plane model of the lower limb, which considered the possibility of
      antagonistic and synergistic muscle action and took account of the load-bearing
      roles of the cruciate ligaments, was applied to a dynamic analysis of level
      walking. It was hypothesized that: (1) the simple, one-sided constraints that
      intra-articular contact forces must be compressive and muscle and ligament forces
      tensile substantially reduce the redundancy of the load-transmitting structures
      of the lower limb, (2) many previously proposed optimization laws for muscle
      selection yield equivalent results, when they are applied to a finite set of
      admissible limiting solutions, and (3) the aforementioned optimization laws, when
      applied to a finite set of admissible limiting solutions, do not adequately
      predict the co-contraction of antagonistic muscles during gait. The problem of
      indeterminacy was resolved by considering all possible limiting solutions of the
      system unknowns on the dynamic equations. Although 498 limiting solutions of nine
      unknowns could arise at each sampled point on the gait cycle, the aforementioned
      one-sided constraints ruled out the large majority of them. It was shown that of
      the 498 possible, the minimum number of simultaneous admissible solutions for any
      subject was as few as three and the maximum number was only 18. The Principles of
      minimal total muscle force, squared muscle force, muscle stress, intra-articular
      contact force and instantaneous muscle power predicted remarkably similar
      patterns of muscle activity over the gait cycle. Of the six tested performance
      criteria, the Principle of minimal total ligament force was the least successful
      in terms of selecting solutions that closely matched the EMG patterns. This
      result implied that the muscles do not always act to protect the knee ligaments
      during gait. Finally, each of the above minimum principles failed to predict any
      antagonistic quadriceps-hamstrings action at the knee and hip around the event of
      heelstrike, although such activity was indicated by electromyography.

PMID- 7730386
TI  - Contact areas and pressure distributions in the subtalar joint.
AB  - We investigated how foot position and ankle arthrodesis affect the contact
      characteristics of the subtalar joint. Nine fresh-frozen specimens of amputated
      lower legs were used. Pressure-sensitive films were inserted into the anterior
      and posterior articulation of the subtalar joint. The contact areas and pressure
      for various foot positions and under axial loads of 600, 1200, and 1800 N were
      determined based on the gray level of the digitized film. In neutral position and
      under a 600 N load, the maximum contact pressure in the subtalar joint was 5.13
      +/- 1.16 MPa. The contact area (1.18 +/- 0.35 cm2) was only 12.7% of the whole
      subtalar articulation area (9.31 +/- 0.66 cm2), and the total force (348.5 +/-
      41.7 N) transmitted via this contact area was about 58% of the applied load (600
      N). Dorsiflexion of the foot increased the contact area and the force
      transmitted, but decreased the average contact pressure in the subtalar joint,
      while the reverse occurred in plantar flexion. Eversion increased the subtalar
      contact stress, whereas inversion up to 10 degrees decreased it. Ankle joint
      arthrodesis shifted the contact areas in the subtalar joint posteriorly in all
      inversion/eversion positions. Moreover, total force transmitted through the
      subtalar joint as well as the contact pressure increased.

PMID- 7730387
TI  - The influence of tendon Youngs modulus, dimensions and instantaneous moment arms
      on the efficiency of human movement.
AB  - The purpose of the study was to examine the influence of passive tendon work on
      the gross mechanical efficiency of human whole body movement. Seven male subjects
      participated in the study. They performed repetitive jumps (like skipping) of
      three different intensities. Metabolic costs and work rates were recorded to
      obtain mechanical efficiencies. Net joint moments were calculated from film
      recordings using inverse dynamics. A general stress-strain relationship for
      tendons was modelled using a quadratic function, including Youngs elastic modulus
      of tendon tissue and tendon dimensions. Instantaneous tendon moment arms for the
      largest leg extensor muscles (m. triceps surae and m. quadriceps femoris) were
      calculated using joint angle-moment arm transfer functions obtained from the
      literature (cadaver studies) and the tendon work was calculated from the net
      joint moments. Gross efficiency values of 0.65-0.69 and efficiency values of 0.77
      0.80 at the approximate level of the muscle-tendon complexes were observed. The
      tendons performed 52-60% of the total work. The enhancement of the muscle-tendon
      efficiency over the maximal theoretical efficiency of the contractile machinery
      (0.30) could exclusively be explained by the contribution of the tendon work. A
      clear negative relationship between repetitive jumping with high mechanical
      efficiency and running economy at 12 km h-1 was found. Using model calculations
      the gross efficiency and the muscle-tendon efficiency were shown to be sensitive
      to tendon Youngs modulus, dimensions and moment arms. The efficiencies were most
      sensitive to changes in the tendon moment arms. A 10% decrease in tendon moment
      arms resulted in a 13% increase in the gross efficiency. Optimization or
      minimisation of the mechanical efficiency by changing the tendon variables 5% was
      followed by changes in mechanical efficiency of +14% and -10%, respectively.

PMID- 7730388
TI  - Mechanical and muscular factors influencing the performance in maximal vertical
      jumping after different prestretch loads.
AB  - The objective of the present work was to study the interaction between the tendon
      elasticity, the muscle activation-loading dynamics, specific actions of the
      biarticular muscles, preloading and jumping performance during maximal vertical
      jumping. Six male expert jumpers participated in the study. They performed
      maximal vertical jumps with five different preloads. The kinematics and dynamics
      of the jumping movements were analysed from force plate and high speed film
      recordings. The amount of elastic energy stored in the tendons of the leg
      extensor muscles was calculated by a generalised tendon model, and the muscle
      coordination was analysed by surface EMG. The best jumping performances were
      achieved in the jumps with low preloads (counter movement jumps and drop jumps
      from 0.3 m). A considerable amount of the energy imposed on the legs by
      prestretch loading was stored in the tendons (26 +/- 3%), but the increased
      performance could not be explained by a contribution of elastic energy to the
      positive work performed during the push off. During the preloading, the involved
      muscles were activated at the onset of the loading. Slow prestretches at the
      onset of muscle activation under relatively low average stretch loads, as
      observed during counter movement jumps and drop jumps from 0.3 m, prevented
      excessive stretching of the muscle fibres in relation to the tendon length
      changes. This consequently conserved the potential of the muscle fibres to
      produce positive work during the following muscle-tendon shortening in concert
      with the release of the tendon strain energy. A significant increase in the
      activity of m. rectus femoris between jumps with and without prestretch indicated
      a pronounced action of m. rectus femoris in a transport of mechanical energy
      produced by the proximal monoarticular m. gluteus maximus at the hip to the knee
      and thereby enhanced the transformation of rotational joint work to translational
      work on the mass centre of the body. The changes in muscle activity were
      reflected in the net muscle powers. Vertical jumping is like most movements
      constrained by the intended direction of the movement. The movements of the body
      segments during the prestretches induced a forward rotation and during the take
      off, a backward rotation of the body. A reciprocal shift in the activities of the
      biarticular m. rectus femoris and m. semitendinosus indicated that these
      rotations were counteracted by changes in the direction of the resultant ground
      reaction vector controlled by these muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7730389
TI  - Fracture toughness of human bone under tension.
AB  - The longitudinal fracture toughnesses of human cortical bone were compared to
      those of bovine cortical bone to test the hypothesis that although human osteonal
      bone is significantly weaker and more compliant than primary (plexiform) bone, it
      is not less tough than primary bone. The fracture toughness indices, critical
      strain energy release rate (Gc) and critical stress intensity factor (Kc), were
      determined for human Haversian bone and bovine bone under tension (Mode I)
      loading using the compact tension method. The effects of thickness, crack growth
      range and anisotropy on fracture indices for slow stable crack growth in cortical
      bone were determined. Plane strain assumptions required for application of linear
      elastic fracture mechanics (LEFM) to bone were investigated. Longitudinal
      oriented fracture toughness tests were used to assess the crack inhibiting effect
      of human bone microstructure on fracture resistance. Human bone Kc calculated
      from the stress concentration formula for 2 and 3 mm thick specimens equaled 4.32
      and 4.05 MN m-3/2, respectively. Human bone Gc calculated from the compliance
      method equaled 827 N m-1 for 2 mm thick specimens and 595 N m-1 for 3 mm thick
      specimens. It was found that crack growth range, thickness and material
      assumptions affect fracture toughness. Kc calculated from Gc using an anisotropic
      relation provided the lowest estimate of Kc and equaled 3.31 MN m-3/2 for 2 mm
      thick specimens and 2.81 MN m-3/2 for 3 mm thick specimens. Both Kc and Gc were
      significantly reduced after being adjusted to ASTM standard thickness using
      ratios determined from bovine bone. The fracture toughness of bovine bone
      relative to human bone ranged from 1.08 to 1.66. This was compared to the
      longitudinal strength of bovine bone relative to the longitudinal strength of
      human bone which is approximately equal to 1.5. We found that even though human
      bone is significantly weaker than bovine bone, relative to its strength, the
      toughness of human and bovine bone are roughly similar, but the data were not
      sufficiently definitive to answer the question of which is tougher.

PMID- 7730390
TI  - Comparison of muscle forces and joint load from an optimization and EMG assisted
      lumbar spine model: towards development of a hybrid approach.
AB  - The purpose of this study was to determine whether the same estimates of
      individual muscle and L4/L5 lumbar joint compressive forces result from an
      optimization (OPT) compared to an electromyography (EMG) assisted approach for
      solving the inderminate moment equilibrium equations in the same anatomical
      model. Four male subjects performed near maximum, isometric, ramp efforts in
      trunk flexion, extension and lateral bending in a testing apparatus. The EMG
      approach was sensitive to subject and trial differences in the magnitudes of
      individual muscle forces needed to produce the same reaction moment. In contrast,
      the OPT method converged on a similar estimate of muscle forces for all subjects
      and trials producing the same moment. The OPT method predicted lower L4/L5 joint
      compression values, on average, by 32, 43 and 23% in trunk extension, flexion and
      lateral bending, respectively, because, unlike the EMG method, it could not
      predict co-contraction of anatomically antagonistic muscles. We incorporated the
      OPT method's advantage of forcing an equilibrium in the reaction moments into the
      EMG method in a new approach we have called 'EMG assisted optimization' (EMGAO).
      Muscle force estimates from the EMG and EMGAO methods differed from those from
      the OPT method, on average, by 123% (RMS) for flexion and extension and by 218%
      for lateral bends. Data from the two approaches result in different conclusions
      about spine mechanics. We have more confidence in the EMG assisted methods
      because they respond to variation in muscle synergy and co-contraction patterns
      commonly observed in different trials and subjects for the same reaction moments.

PMID- 7730391
TI  - A device for synchronizing biomechanical data with cine film.
AB  - Biomechanists are faced with two problems in synchronizing continuous
      physiological data to discrete, frame-based kinematic data from films. First, the
      accuracy of most synchronization techniques is good only to one frame and hence
      depends on framing rate. Second, even if perfectly correlated at the beginning of
      a 'take', the film and physiological data may become progressively desynchronized
      as the 'take' proceeds. A system is described, which provides synchronization
      between cine film and continuous physiological data with an accuracy of +/- 0.2
      ms, independent of framing rate and the duration of the film 'take'. Shutter
      pulses from the camera were output to a computer recording system where they were
      recorded and counted, and to a digital device which counted the pulses and
      illuminated the count on the bank of LEDs which was filmed with the subject.
      Synchronization was performed by using the rising edge of the shutter pulse and
      by comparing the frame number imprinted on the film to the frame number recorded
      by the computer system. In addition to providing highly accurate synchronization
      over long film 'takes', this system provides several other advantages. First,
      having frame numbers imprinted both on the film and computer record greatly
      facilitates analysis. Second, the LEDs were designed to show the 'take number'
      while the camera is coming up to speed, thereby avoiding the use of cue cards
      which disturb the animal. Finally, use of this device results in considerable
      savings in film.

PMID- 7730392
TI  - The psoas major muscle: a three-dimensional geometric study.
AB  - The purpose of this study was to use anatomical data obtained from cadavers, and
      geometrical scaling data obtained from MRI scans of living subjects, to assess
      the line of action and mechanical function of the psoas major muscle in three
      dimensions about each lumbar spine level. In addition, the line of action of the
      psoas major was documented as a function of lordosis. A total of seven cadavers
      were dissected from which fibre/tendon architecture was measured, while MRI scans
      were performed on 15 males to obtain centroid paths and area scales of the muscle
      over its length. In this way, the curving path of muscle line of action was
      accommodated together with force and moment predictions that recognized the
      presence of a tendon at lower lumbar levels (up to L3 in some subjects)
      significantly increasing the stress. Results confirm that the mechanics of the
      psoas cannot be adequately represented with a series of straight line vectors
      from vertebral origins to insertion. Moreover, the mechanical action of the psoas
      major does not change as a function of lumbar spine lordosis as the muscle path
      of action changes in accordance with changes in spine posture. Functionally,
      contrary to claims, the psoas cannot act as a 'derotator' of the spine, does not
      impose large shear forces on the spine in any posture except at L5-S1, and cannot
      have major affects to 'control lordosis'. It has the potential to stabilize the
      lumbar spine with compressive loading and with bilateral activation, to laterally
      flex it, and can create large anterior shear forces but only at L5-S1.

PMID- 7730393
TI  - Footswitch system for measurement of the temporal parameters of gait.
AB  - Gait analysis relies upon accurate measurement of initial and end foot contact
      times. These times act as a reference point for correlating all other gait data
      and as a mean of distinguishing normal and pathologic gait. We have developed a
      simple, inexpensive footswitch system that provides accurate estimates of the
      start and end of stance phase for sequential steps. The estimates of the
      beginning and end of stance phase do not require custom footwear, extensive
      calibration, or precise placement of the sensor within the shoe. The system is
      based on a commercially available transducer and can be readily reproduced for
      use in a laboratory setting for less than $50. We describe this system, as well
      as its validation. To assess the accuracy of this footswitch system, we compared
      footswitch based estimates of initial and end foot contact times with those
      obtained using a force platform as 10 people took 30 steps (10 each at slow,
      normal and fast walking rates) across a force platform. Both estimates coincided
      within +/- 10 ms (mean: 0 +/- 3 ms; N = 300) for the start of stance phase and
      within +/- 22 ms (mean: -1 +/- 8 ms; N = 300) for the end of stance phase. For
      stance duration, the differences ranged from -24 to 28 ms (mean: 1 +/- 10 ms; N =
      300). In combination, these measures can be used to estimate stance duration to
      within 3% of force plate determined values for steps with stance durations
      ranging from 446 to 1594 ms. Estimates of swing and stride duration also are
      within 5% of force plate determined values. This system should therefore prove to
      be a useful tool for augmenting laboratory based investigations of gait.

PMID- 7730394
TI  - Martin, R.B., Liptai, L., Yerbi, S., and Williams, K.R. (1994). The relationship
      between mass and acceleration for impacts on padded surfaces.

PMID- 7730395
TI  - A nuclear localization domain in the hnRNP A1 protein.
AB  - The heterogeneous nuclear RNP (hnRNP) A1 protein is one of the major pre
      mRNA/mRNA binding proteins in eukaryotic cells and one of the most abundant
      proteins in the nucleus. It is localized to the nucleoplasm and it also shuttles
      between the nucleus and the cytoplasm. The amino acid sequence of A1 contains two
      RNP motif RNA-binding domains (RBDs) at the amino terminus and a glycine-rich
      domain at the carboxyl terminus. This configuration, designated 2x RBD-Gly, is
      representative of perhaps the largest family of hnRNP proteins. Unlike most
      nuclear proteins characterized so far, A1 (and most 2x RBD-Gly proteins) does not
      contain a recognizable nuclear localization signal (NLS). We have found that a
      segment of ca. 40 amino acids near the carboxyl end of the protein (designated
      M9) is necessary and sufficient for nuclear localization; attaching this segment
      to the bacterial protein beta-galactosidase or to pyruvate kinase completely
      localized these otherwise cytoplasmic proteins to the nucleus. The RBDs and
      another RNA binding motif found in the glycine-rich domain, the RGG box, are not
      required for A1 nuclear localization. M9 is a novel type of nuclear localization
      domain as it does not contain sequences similar to classical basic-type NLS.
      Interestingly, sequences similar to M9 are found in other nuclear RNA-binding
      proteins including hnRNP A2.

PMID- 7730396
TI  - A possible mechanism for the inhibition of ribosomal RNA gene transcription
      during mitosis.
AB  - When cells enter mitosis, RNA synthesis ceases. Yet the RNA polymerase I (pol I)
      transcription machinery involved in the production of pre-rRNA remains bound to
      the nucleolus organizing region (NOR), the chromosome site harboring the tandemly
      repeated rRNA genes. Here we examine whether rDNA transcription units are
      transiently blocked or "frozen" during mitosis. By using fluorescent in situ
      hybridization we were unable to detect nascent pre-rRNA chains on the NORs of
      mouse 3T3 and rat kangaroo PtK2 cells. Appropriate controls showed that our
      approach was sensitive enough to visualize, at the light microscopic level,
      individual transcriptionally active rRNA genes both in situ after experimental
      unfolding of nucleoli and in chromatin spreads ("Miller spreads"). Analysis of
      the cell cycle-dependent redistribution of transcript-associated components also
      revealed that most transcripts are released from the rDNA at mitosis. Upon
      disintegration of the nucleolus during mitosis, U3 small nucleolar RNA (snoRNA)
      and the nucleolar proteins fibrillarin and nucleolin became dispersed throughout
      the cytoplasm and were excluded from the NORs. Together, our data rule out the
      presence of "frozen Christmas-trees" at the mitotic NORs but are compatible with
      the view that inactive pol I remains on the rDNA. We propose that expression of
      the rRNA genes is regulated during mitosis at the level of transcription
      elongation, similarly to what is known for a number of genes transcribed by pol
      II. Such a mechanism may explain the decondensed state of the NOR chromatin and
      the immediate transcriptional reactivation of the rRNA genes following mitosis.

PMID- 7730397
TI  - Reconstitution of vesiculated Golgi membranes into stacks of cisternae:
      requirement of NSF in stack formation.
AB  - We have developed an in vitro system to study the biochemical events in the
      fusion of ilimaquinone (IQ) induced vesiculated Golgi membranes (VGMs) into
      stacks of cisternae. The Golgi complex in intact normal rat kidney cells (NRK) is
      vesiculated by treatment with IQ. The cells are washed to remove the drug and
      then permeabilized by a rapid freeze-thaw procedure. VGMs of 60 nm average
      diameter assemble into stacks of Golgi cisternae by a process that is temperature
      dependent, requires ATP and a high speed supernatant from cell extract (cytosol),
      as revealed by immunofluorescence and electron microscopy. The newly assembled
      stacks are functionally active in vesicular protein transport and contain
      processing enzymes that carry out Golgi specific modifications of glycoproteins.
      The fusion of VGMs requires NSF, a protein known to promote fusion of transport
      vesicles with the target membrane in the exocytic and endocytic pathways.
      Immunoelectron microscopy using Golgi specific anti-mannosidase II antibody
      reveals that VGMs undergo sequential changes in their morphology, whereby they
      first fuse to form larger vesicles of 200-300-nm average diameter which
      subsequently extend into tubular elements and finally assemble into stacks of
      cisternae.

PMID- 7730399
TI  - Reassembly of Golgi stacks from mitotic Golgi fragments in a cell-free system.
AB  - Rat liver Golgi stacks were incubated with mitotic cytosol for 30 min at 37
      degrees C to generate mitotic Golgi fragments comprising vesicles, tubules, and
      cisternal remnants. These were isolated and further incubated with rat liver
      cytosol for 60 min. The earliest intermediate observed by electron microscopy was
      a single, curved cisterna with tubular networks fused to the cisternal rims.
      Elongation of this cisterna was accompanied by stacking and further growth at the
      cisternal rims. Stacks also fused laterally so that the typical end product was a
      highly curved stack of 2-3 cisternae mostly enclosing an electron-lucent space.
      Reassembly occurred in the presence of nocodazole or cytochalasin B but not at 4
      degrees C or in the absence of energy supplied in the form of ATP and GTP.
      Pretreatment of the mitotic fragments and cytosol with N-ethylmaleimide (NEM)
      also prevented reassembly. GTP gamma S and A1F prevented reassembly when added
      during fragmentation but not when added to the reassembly mixture. In fact, GTP
      gamma S stimulated reassembly such that all cisternae were stacked at the end of
      the incubation and comprised 40% of the total membrane. In contrast, microcystin
      inhibited stacking so that only single cisternae accumulated. Together these
      results provide a detailed picture of the reassembly process and open up the
      study of the architecture of the Golgi apparatus to a combined morphological and
      biochemical analysis.

PMID- 7730398
TI  - Laminin mediates tissue-specific gene expression in mammary epithelia.
AB  - Tissue-specific gene expression in mammary epithelium is dependent on the
      extracellular matrix as well as hormones. There is good evidence that the
      basement membrane provides signals for regulating beta-casein expression, and
      that integrins are involved in this process. Here, we demonstrate that in the
      presence of lactogenic hormones, laminin can direct expression of the beta-casein
      gene. Mouse mammary epithelial cells plated on gels of native laminin or laminin
      entactin undergo functional differentiation. On tissue culture plastic, mammary
      cells respond to soluble basement membrane or purified laminin, but not other
      extracellular matrix components, by synthesizing beta-casein. In mammary cells
      transfected with chloramphenicol acetyl transferase reporter constructs, laminin
      activates transcription from the beta-casein promoter through a specific enhancer
      element. The inductive effect of laminin on casein expression was specifically
      blocked by the E3 fragment of the carboxy terminal region of the alpha 1 chain of
      laminin, by antisera raised against the E3 fragment, and by a peptide
      corresponding to a sequence within this region. Our results demonstrate that
      laminin can direct tissue-specific gene expression in epithelial cells through
      its globular domain.

PMID- 7730400
TI  - Yeast Gaa1p is required for attachment of a completed GPI anchor onto proteins.
AB  - Anchoring of proteins to membranes by glycosylphosphatidylinositols (GPIs) is
      ubiquitous among all eukaryotes and heavily used by parasitic protozoa. GPI is
      synthesized and transferred en bloc to form GPI-anchored proteins. The key enzyme
      in this process is a putative GPI:protein transamidase that would cleave a
      peptide bond near the COOH terminus of the protein and attach the GPI by an amide
      linkage. We have identified a gene, GAA1, encoding an essential ER protein
      required for GPI anchoring. gaal mutant cells synthesize the complete GPI anchor
      precursor at nonpermissive temperatures, but do not attach it to proteins.
      Overexpression of GAA1 improves the ability of cells to attach anchors to a GPI
      anchored protein with a mutant anchor attachment site. Therefore, Gaa1p is
      required for a terminal step of GPI anchor attachment and could be part of the
      putative GPI:protein transamidase.

PMID- 7730401
TI  - Insulin-sensitive targeting of the GLUT4 glucose transporter in L6 myoblasts is
      conferred by its COOH-terminal cytoplasmic tail.
AB  - The GLUT4 glucose transporter appears to be targeted to a unique insulin
      sensitive intracellular membrane compartment in fat and muscle cells. Insulin
      stimulates glucose transport in these cell types by mediating the partial
      redistribution of GLUT4 from this intracellular compartment to the plasma
      membrane. The structural basis for the unique targeting behavior of GLUT4 was
      investigated in the insulin-sensitive L6 myoblast cell line. Analysis of
      immunogold-labeled cells of independent clonal lines by electron microscopy
      indicated that 51-53% of GLUT1 was present in the plasma membrane in the basal
      state. Insulin did not significantly affect this distribution. In contrast, only
      4.2-6.1% of GLUT4 was present in the plasma membrane of basal L6 cells and
      insulin increased this percentage by 3.7-6.1-fold. Under basal conditions and
      after insulin treatment, GLUT4 was detected in tubulovesicular structures, often
      clustered near Golgi stacks, and in endosome-like vesicles. Analysis of 25
      chimeric transporters consisting of reciprocal domains of GLUT1 and GLUT4 by
      confocal immunofluorescence microscopy indicated that only the final 25 amino
      acids of the COOH-terminal cytoplasmic tail of GLUT4 were both necessary and
      sufficient for the targeting pattern observed for GLUT4. A dileucine motif
      present in the COOH-terminal tail of GLUT4 was found to be necessary, but not
      sufficient, for intracellular targeting. Contrary to previous studies, the NH2
      terminus of GLUT4 did not affect the subcellular distribution of chimeras.
      Analysis of a chimera containing the COOH-terminal tail of GLUT4 by immunogold
      electron microscopy indicated that its subcellular distribution in basal cells
      was very similar to that of wild-type GLUT4 and that its content in the plasma
      membrane increased 6.8-10.5-fold in the presence of insulin. Furthermore, only
      the chimera containing the COOH terminus of GLUT4 enhanced insulin responsive 2
      deoxyglucose uptake. GLUT1 and two other chimeras lacking the COOH terminus of
      GLUT4 were studied by immunogold electron microscopy and did not demonstrate
      insulin-mediated changes in subcellular distribution. The NH2-terminal
      cytoplasmic tail of GLUT4 did not confer intracellular sequestration and did not
      cause altered subcellular distribution in the presence of insulin. Intracellular
      targeting of one chimera to non-insulin-sensitive compartments was also observed.
      We conclude that the COOH terminus of GLUT4 is both necessary and sufficient to
      confer insulin-sensitive subcellular targeting of chimeric glucose transporters
      in L6 myoblasts.

PMID- 7730402
TI  - Molecular architecture of membranes involved in excitation-contraction coupling
      of cardiac muscle.
AB  - Peripheral couplings are junctions between the sarcoplasmic reticulum (SR) and
      the surface membrane (SM). Feet occupy the SR/SM junctional gap and are
      identified as the SR calcium release channels, or ryanodine receptors (RyRs). In
      cardiac muscle, the activation of RyRs during excitation-contraction (e-c)
      coupling is initiated by surface membrane depolarization, followed by the opening
      of surface membrane calcium channels, the dihydropyridine receptors (DHPRs). We
      have studied the disposition of DHPRs and RyRs, and the structure of peripheral
      couplings in chick myocardium, a muscle that has no transverse tubules.
      Immunolabeling shows colocalization of RyRs and DHPRs in clusters at the fiber's
      periphery. The positions of DHPR and RyR clusters change coincidentally during
      development. Freeze-fracture of the surface membrane reveals the presence of
      domains (junctional domains) occupied by clusters of large particles. Junctional
      domains in the surface membrane and arrays of feet in the junctional gap have
      similar sizes and corresponding positions during development, suggesting that
      both are components of peripheral couplings. As opposed to skeletal muscle,
      membrane particles in junctional domains of cardiac muscle do not form tetrads.
      Thus, despite their proximity to the feet, they do not appear to be specifically
      associated with them. Two observations establish the identify of the structurally
      identified feet arrays/junctional domain complexes with the immunocytochemically
      defined RyRs/DHPRs coclusters: the concomitant changes during development and the
      identification of feet as the cytoplasmic domains of RyRs. We suggest that the
      large particles in junctional domains of the surface membrane represent DHPRs.
      These observations have two important functional consequences. First, the
      apposition of DHPRs and RyRs indicates that most of the inward calcium current
      flows into the restricted space where feet are located. Secondly, contrary to
      skeletal muscle, presumptive DHPRs do not show a specific association with the
      feet, which is consistent with a less direct role of charge movement in cardiac
      than in skeletal e-c coupling.

PMID- 7730403
TI  - Immunolocalization of sarcolemmal dihydropyridine receptor and sarcoplasmic
      reticular triadin and ryanodine receptor in rabbit ventricle and atrium.
AB  - The subcellular distribution of sarcolemmal dihydropyridine receptor (DHPR) and
      sarcoplasmic reticular triadin and Ca2+ release channel/ryanodine receptor (RyR)
      was determined in adult rabbit ventricle and atrium by double labeling
      immunofluorescence and laser scanning confocal microscopy. In ventricular muscle
      cells the immunostaining was observed primarily as transversely oriented punctate
      bands spaced at approximately 2-micron intervals along the whole length of the
      muscle fibers. Image analysis demonstrated a virtually complete overlap of the
      staining patterns of the three proteins, suggesting their close association at or
      near dyadic couplings that are formed where the sarcoplasmic reticulum (SR) is
      apposed to the surface membrane or its infoldings, the transverse (T-) tubules.
      In rabbit atrial cells, which lack an extensive T-tubular system, DHPR-specific
      staining was observed to form discrete spots along the sarcolemma but was absent
      from the interior of the fibers. In atrium, punctate triadin- and RyR-specific
      staining was also observed as spots at the cell periphery and image analysis
      indicated that the three proteins were co-localized at, or just below, the
      sarcolemma. In addition, in the atrial cells triadin- and RyR-specific staining
      was observed to form transverse bands in the interior cytoplasm at regularly
      spaced intervals of approximately 2 micron. Electron microscopy suggested that
      this cytoplasmic staining was occurring in regions where substantial amounts of
      extended junctional SR were present. These data indicate that the DHPR
      codistributes with triadin and the RyR in rabbit ventricle and atrium, and
      furthermore suggest that some of the SR Ca2+ release channels in atrium may be
      activated in the absence of a close association with the DHPR.

PMID- 7730404
TI  - Mechanisms of thin filament assembly in embryonic chick cardiac myocytes:
      tropomodulin requires tropomyosin for assembly.
AB  - Tropomodulin is a pointed end capping protein for tropomyosin-coated actin
      filaments that is hypothesized to play a role in regulating the precise lengths
      of striated muscle thin filaments (Fowler, V. M., M. A. Sussman, P. G. Miller, B.
      E. Flucher, and M. P. Daniels. 1993. J. Cell Biol. 120:411-420; Weber, A., C. C.
      Pennise, G. G. Babcock, and V. M. Fowler. 1994, J. Cell Biol. 127:1627-1635). To
      gain insight into the mechanisms of thin filament assembly and the role of
      tropomodulin therein, we have characterized the temporal appearance, biosynthesis
      and mechanisms of assembly of tropomodulin onto the pointed ends of thin
      filaments during the formation of striated myofibrils in primary embryonic chick
      cardiomyocyte cultures. Our results demonstrate that tropomodulin is not
      assembled coordinately with other thin filament proteins. Double
      immunofluorescence staining and ultrastructural immunolocalization demonstrate
      that tropomodulin is incorporated in its characteristic sarcomeric location at
      the pointed ends of the thin filaments after the thin filaments have become
      organized into periodic I bands. In fact, tropomodulin assembles later than all
      other well characterized myofibrillar proteins studied including: actin,
      tropomyosin, alpha-actinin, titin, myosin and C-protein. Nevertheless, at steady
      state, a significant proportion (approximately 39%) of tropomodulin is present in
      a soluble pool throughout myofibril assembly. Thus, the absence of tropomodulin
      in some striated myofibrils is not due to limiting quantities of the protein. In
      addition, kinetic data obtained from [35S]methionine pulse-chase experiments
      indicate that tropomodulin assembles more slowly into myofibrils than does
      tropomyosin. This observation, together with results obtained using a novel
      permeabilized cell model for thin filament assembly, indicate that tropomodulin
      assembly is dependent on the prior association of tropomyosin with actin
      filaments. We conclude that tropomodulin is a late marker for the assembly of
      striated myofibrils in cardiomyocytes; its assembly appears to be linked to their
      maturity. We propose that tropomodulin is involved in maintaining and stabilizing
      the final lengths of thin filaments after they are assembled.

PMID- 7730405
TI  - Forced expression of chimeric human fibroblast tropomyosin mutants affects
      cytokinesis.
AB  - Human fibroblasts generate at least eight tropomyosin (TM) isoforms (hTM1, hTM2,
      hTM3, hTM4, hTM5, hTM5a, hTM5b, and hTMsm alpha) from four distinct genes, and we
      have previously demonstrated that bacterially produced chimera hTM5/3 exhibits an
      unusually high affinity for actin filaments and a loss of the salt dependence
      typical for TM-actin binding (Novy, R.E., J. R. Sellers, L.-F. Liu, and J.J.-C.
      Lin, 1993. Cell Motil. & Cytoskeleton. 26: 248-261). To examine the functional
      consequences of expressing this mutant TM isoform in vivo, we have transfected
      CHO cells with the full-length cDNA for hTM5/3 and compared them to cells
      transfected with hTM3 and hTM5. Immunofluorescence microscopy reveals that stably
      transfected CHO cells incorporate force-expressed hTM3 and hTM5 into stress
      fibers with no significant effect on general cell morphology, microfilament
      organization or cytokinesis. In stable lines expressing hTM5/3, however, cell
      division is slow and sometimes incomplete. The doubling time and the incidence of
      multinucleate cells in the stable hTM5/3 lines roughly parallel expression
      levels. A closely related chimeric isoform hTM5/2, which differs only in the
      internal, alternatively spliced exon also produces defects in cytokinesis,
      suggesting that normal TM function may involve coordination between the amino and
      carboxy terminal regions. This coordination may be prevented in the chimeric
      mutants. As bacterially produced hTM5/3 and hTM5/2 can displace hTM3 and hTM5
      from actin filaments in vitro, it is likely that CHO-expressed hTM5/3 and hTM5/2
      can displace endogenous TMs to act dominantly in vivo. These results support a
      role for nonmuscle TM isoforms in the fine tuning of microfilament organization
      during cytokinesis. Additionally, we find that overexpression of TM does not
      stabilize endogenous microfilaments, rather, the hTM-expressing cells are
      actually more sensitive to cytochalasin B. This suggests that regulation of
      microfilament integrity in vivo requires stabilizing factors other than, or in
      addition to, TM.

PMID- 7730406
TI  - The Drosophila kinesin-like protein KLP3A is a midbody component required for
      central spindle assembly and initiation of cytokinesis.
AB  - We describe here a new member of the kinesin superfamily in Drosophila, KLP3A
      (Kinesin-Like-Protein-at-3A). The KLP3A protein localizes to the equator of the
      central spindle during late anaphase and telophase of male meiosis. Mutations in
      the KLP3A gene disrupt the interdigitation of microtubules in spermatocyte
      central spindles. Despite this defect, anaphase B spindle elongation is not
      obviously aberrant. However, cytokinesis frequently fails after both meiotic
      divisions in mutant testes. Together, these findings strongly suggest that the
      KLP3A presumptive motor protein is a critical component in the establishment or
      stabilization of the central spindle. Furthermore, these results imply that the
      central spindle is the source of signals that initiate the cleavage furrow in
      higher cells.

PMID- 7730407
TI  - The Drosophila cell cycle gene fizzy is required for normal degradation of
      cyclins A and B during mitosis and has homology to the CDC20 gene of
      Saccharomyces cerevisiae.
AB  - The Drosophila cell cycle gene fizzy (fzy) is required for normal execution of
      the metaphase-anaphase transition. We have cloned fzy, and confirmed this by P
      element mediated germline transformation rescue. Sequence analysis predicts that
      fzy encodes a protein of 526 amino acids, the carboxy half of which has
      significant homology to the Saccharomyces cerevisiae cell cycle gene CDC20. A
      monoclonal antibody against fzy detects a single protein of the expected size, 59
      kD, in embryonic extracts. In early embryos fzy is expressed in all proliferating
      tissues; in late embryos fzy expression declines in a tissue-specific manner
      correlated with cessation of cell division. During interphase fzy protein is
      present in the cytoplasm; while in mitosis fzy becomes ubiquitously distributed
      throughout the cell except for the area occupied by the chromosomes. The
      metaphase arrest phenotype caused by fzy mutations is associated with failure to
      degrade both mitotic cyclins A and B, and an enrichment of spindle microtubules
      at the expense of astral microtubules. Our data suggest that fzy function is
      required for normal cell cycle-regulated proteolysis that is necessary for
      successful progress through mitosis.

PMID- 7730408
TI  - A cell cycle checkpoint monitors cell morphogenesis in budding yeast.
AB  - Checkpoint controls are regulatory pathways that inhibit cell cycle progression
      in cells that have not faithfully completed a prior step in the cell cycle. In
      the budding yeast Saccharomyces cerevisiae, DNA replication and spindle assembly
      are monitored by checkpoint controls that prevent nuclear division in cells that
      have failed to complete these processes. During the normal cell cycle, bud
      formation is temporally coincident with DNA replication and spindle assembly, and
      the nucleus divides along the mother-bud axis in mitosis. In this report, we show
      that inhibition of bud formation also causes a dramatic delay in nuclear
      division. This allows cells to recover from a transient disruption of cell
      polarity without becoming binucleate. The delay occurs after DNA replication and
      spindle assembly, and results from delayed activation of the master cell cycle
      regulatory kinase, Cdc28. Cdc28 activation is inhibited by phosphorylation of
      Cdc28 on tyrosine 19, and by delayed accumulation of the B-type cyclins Clb1 and
      Clb2. These results suggest the existence of a novel checkpoint that monitors
      cell morphogenesis in budding yeast.

PMID- 7730409
TI  - Patterns of bud-site selection in the yeast Saccharomyces cerevisiae.
AB  - Cells of the yeast Saccharomyces cerevisiae select bud sites in either of two
      distinct spatial patterns, known as axial (expressed by a and alpha cells) and
      bipolar (expressed by a/alpha cells). Fluorescence, time-lapse, and scanning
      electron microscopy have been used to obtain more precise descriptions of these
      patterns. From these descriptions, we conclude that in the axial pattern, the new
      bud forms directly adjacent to the division site in daughter cells and directly
      adjacent to the immediately preceding division site (bud site) in mother cells,
      with little influence from earlier sites. Thus, the division site appears to be
      marked by a spatial signal(s) that specifies the location of the new bud site and
      is transient in that it only lasts from one budding event to the next. Consistent
      with this conclusion, starvation and refeeding of axially budding cells results
      in the formation of new buds at nonaxial sites. In contrast, in bipolar budding
      cells, both poles are specified persistently as potential bud sites, as shown by
      the observations that a pole remains competent for budding even after several
      generations of nonuse and that the poles continue to be used for budding after
      starvation and refeeding. It appears that the specification of the two poles as
      potential bud sites occurs before a daughter cell forms its first bud, as a
      daughter can form this bud near either pole. However, there is a bias towards use
      of the pole distal to the division site. The strength of this bias varies from
      strain to strain, is affected by growth conditions, and diminishes in successive
      cell cycles. The first bud that forms near the distal pole appears to form at the
      very tip of the cell, whereas the first bud that forms near the pole proximal to
      the original division site (as marked by the birth scar) is generally somewhat
      offset from the tip and adjacent to (or overlapping) the birth scar. Subsequent
      buds can form near either pole and appear almost always to be adjacent either to
      the birth scar or to a previous bud site. These observations suggest that the
      distal tip of the cell and each division site carry persistent signals that can
      direct the selection of a bud site in any subsequent cell cycle.

PMID- 7730410
TI  - Role of Bud3p in producing the axial budding pattern of yeast.
AB  - Yeast cells can select bud sites in either of two distinct spatial patterns. a
      cells and alpha cells typically bud in an axial pattern, in which both mother and
      daughter cells form new buds adjacent to the preceding division site. In
      contrast, a/alpha cells typically bud in a bipolar pattern, in which new buds can
      form at either pole of the cell. The BUD3 gene is specifically required for the
      axial pattern of budding: mutations of BUD3 (including a deletion) affect the
      axial pattern but not the bipolar pattern. The sequence of BUD3 predicts a
      product (Bud3p) of 1635 amino acids with no strong or instructive similarities to
      previously known proteins. However, immunofluorescence localization of Bud3p has
      revealed that it assembles in an apparent double ring encircling the mother-bud
      neck shortly after the mitotic spindle forms. The Bud3p structure at the neck
      persists until cytokinesis, when it splits to yield a single ring of Bud3p
      marking the division site on each of the two progeny cells. These single rings
      remain for much of the ensuing unbudded phase and then disassemble. The Bud3p
      rings are indistinguishable from those of the neck filament-associated proteins
      (Cdc3p, Cdc10p, Cdc11p, and Cdc12p), except that the latter proteins assemble
      before bud emergence and remain in place for the duration of the cell cycle. Upon
      shift of a temperature-sensitive cdc12 mutant to restrictive temperature,
      localization of both Bud3p and the neck filament-associated proteins is rapidly
      lost. In addition, a haploid cdc11 mutant loses its axial-budding pattern upon
      shift to restrictive temperature. Taken together, the data suggest that Bud3p and
      the neck filaments are linked in a cycle in which each controls the position of
      the other's assembly: Bud3p assembles onto the neck filaments in one cell cycle
      to mark the site for axial budding (including assembly of the new ring of neck
      filaments) in the next cell cycle. As the expression and localization of Bud3p
      are similar in a, alpha, and a/alpha cells, additional regulation must exist such
      that Bud3p restricts the position of bud formation in a and alpha cells but not
      in a/alpha cells.

PMID- 7730411
TI  - Cells differentiating into neuroectoderm undergo apoptosis in the absence of
      functional retinoblastoma family proteins.
AB  - The retinoblastoma (RB) protein is present at low levels in early mouse embryos
      and in pluripotent P19 embryonal carcinoma cells; however, the levels of RB rise
      dramatically in neuroectoderm formed both in embryos and in differentiating
      cultures of P19 cells. To investigate the effect of inactivating RB and related
      proteins p107 and p130, we transfected P19 cells with genes encoding mutated
      versions of the adenovirus E1A protein that bind RB and related proteins. When
      these E1A-expressing P19 cells were induced to differentiate into neuroectoderm,
      there was a striking rise in the expression of c-fos and extensive cell death.
      The ultrastructural and biochemical characteristics of the dying cells were
      indicative of apoptosis. The dying cells were those committed to the neural
      lineages because neurons and astrocytes were lost from differentiating cultures.
      Cell death was dependent on the ability of the E1A protein to bind RB and related
      proteins. Our results suggest that proteins of the RB family are essential for
      the development of the neural lineages and that the absence of functional RB
      activity triggers apoptosis of differentiating neuroectodermal cells.

PMID- 7730412
TI  - Calcitonin gene-related peptide promotes Schwann cell proliferation.
AB  - Schwann cells in culture divide in response to defined mitogens such as PDGF and
      glial growth factor (GGF), but proliferation is greatly enhanced if agents such
      as forskolin, which increases Schwann cell intracellular cAMP, are added at the
      same time as PDGF or GGF (Davis, J. B., and P. Stroobant. 1990. J. Cell Biol.
      110:1353-1360). The effect of forskolin is probably due to an increase in numbers
      of PDGF receptors (Weinmaster, G., and G. Lemke. 1990. EMBO (Eur. Mol. Biol.
      Organ.) J. 9:915-920. Neuropeptides and beta-adrenergic agonists have been
      reported to have no effect on potentiating the mitogenic response of either PDGF
      or GGF. We show that the neuropeptide calcitonin gene-related peptide (CGRP)
      increases Schwann cell cAMP levels, but the cells rapidly desensitize. We
      therefore stimulated the cells in pulsatile fashion to partly overcome the
      effects of desensitization and show that CGRP can synergize with PDGF to
      stimulate Schwann cell proliferation, and that CGRP is as effective as forskolin
      in the pulsatile regime. CGRP is a good substrate for the neutral endopeptidase
      24.11. Schwann cells in vivo have this protease on their surface, so the action
      of CGRP could be terminated by this enzyme and desensitization prevented. We
      therefore suggest that CGRP may play an important role in stimulating Schwann
      cell proliferation by regulating the response of mitogenic factors such as PDGF.

PMID- 7730413
TI  - Ca2+ waves in PC12 neurites: a bidirectional, receptor-oriented form of Ca2+
      signaling.
AB  - Spatial and temporal aspects of Ca2+ signaling were investigated in PC12 cells
      differentiated with nerve growth factor, the well known nerve cell model.
      Activation of receptors coupled to polyphosphoinositide hydrolysis gave rise in a
      high proportion of the cells to Ca2+ waves propagating non decrementally and at
      constant speed (2-4 microns/s at 18 degrees C and approximately 10-fold faster at
      37 degrees C) along the neurites. These waves relied entirely on the release of
      Ca2+ from intracellular stores since they could be generated even when the cells
      were incubated in Ca(2+)-free medium. In contrast, when the cells were
      depolarized with high K+ in Ca(2+)-containing medium, increases of cytosolic Ca2+
      occurred in the neurites but failed to evolve into waves. Depending on the
      receptor agonist employed (bradykinin and carbachol versus ATP) the orientation
      of the waves could be opposite, from the neurite tip to the cell body or vice
      versa, suggesting different and specific distribution of the responsible surface
      receptors. Cytosolic Ca2+ imaging results, together with studies of inositol
      1,4,5-trisphosphate generation in intact cells and inositol 1,4,5-trisphosphate
      induced Ca2+ release from microsomes, revealed the sustaining process of the
      waves to be discharge of Ca2+ from the inositol 1,4,5-trisphosphate- (and not the
      ryanodine-) sensitive stores distributed along the neurites. The activation of
      the cognate receptor appears to result from the coordinate action of the second
      messenger and Ca2+. Because of their properties and orientation, the waves could
      participate in the control of not only conventional cell activities, but also
      excitability and differential processing of inputs, and thus of electrochemical
      computation in nerve cells.

PMID- 7730414
TI  - A novel mammalian myosin I from rat with an SH3 domain localizes to Con A
      inducible, F-actin-rich structures at cell-cell contacts.
AB  - In an effort to determine diversity and function of mammalian myosin I molecules,
      we report here the cloning and characterization of myr 3 (third unconventional
      myosin from rat), a novel mammalian myosin I from rat tissues that is related to
      myosin I molecules from protozoa. Like the protozoan myosin I molecules, myr 3
      consists of a myosin head domain, a single light chain binding motif, and a tail
      region that includes a COOH-terminal SH3 domain. However, myr 3 lacks the
      regulatory phosphorylation site present in the head domain of protozoan myosin I
      molecules. Evidence was obtained that the COOH terminus of the tail domain is
      involved in regulating F-actin binding activity of the NH2-terminal head domain.
      The light chain of myr 3 was identified as the Ca(2+)-binding protein calmodulin.
      Northern blot and immunoblot analyses revealed that myr 3 is expressed in many
      tissues and cell lines. Immunofluorescence studies with anti-myr 3 antibodies in
      NRK cells demonstrated that myr 3 is localized in the cytoplasm and in elongated
      structures at regions of cell-cell contact. These elongated structures contained
      F-actin and alpha-actinin but were devoid of vinculin. Incubation of NRK cells
      with Con A stimulated the formation of myr 3-containing structures along cell
      cell contacts. These results suggest for myr 3 a function mediated by cell-cell
      contact.

PMID- 7730415
TI  - Keratinocyte growth factor is a bifunctional regulator of HPV16 DNA-immortalized
      cervical epithelial cells.
AB  - Various factors are known to regulate cell growth and differentiation in
      epithelial-mesenchymal interactions. Keratinocyte growth factor (KGF), an
      epithelial-specific cytokine produced by dermal fibroblasts and other mesenchymal
      cells, appears to affect growth, migration, and differentiation in epithelial
      mesenchymal interactions. We have previously shown that human embryonic skin
      fibroblasts induce anchorage-independent growth of HPV16 DNA-immortalized human
      uterine exocervical epithelial cells (HCE16/3 cell line) in cocultures of HCE16/3
      cells and fibroblasts. Here we report that KGF may be a major factor influencing
      growth and behavior of HCE16/3 cells in the coculture system. KGF stimulated both
      DNA synthesis and proliferation of normal human cervical epithelial (HCE) cells
      and HCE16/3 cells and the increase was stronger in HCE16/3 cells than in HCE
      cells. SiHa cells, a cervical carcinoma cell line with integrated HPV16 DNA, did
      not respond to the KGF mitogen signal. KGF receptor (KGFR) studies suggested that
      the different responses to the KGF mitogen signal may be correlated with KGFR. In
      addition, KGF alone was able to induce anchorage-independent growth of HCE16/3
      cells, suggesting a potential role for KGF in the transformation process of
      epithelial cells. However, the transcription of HPV16 early genes was suppressed
      by KGF in the immortalized HCE16/3 cells, and this appeared to be due to
      transcriptional repression rather than a posttranscriptional process according to
      nuclear run-on analysis. In contrast, viral gene expression was not affected by
      KGF in SiHa cells. Our results suggest that KGF is a bifunctional growth factor
      in the HPV-immortalized cells, a positive regulator of cell growth and negative
      regulator of HPV16 early gene expression.

PMID- 7730416
TI  - Transglutaminase-catalyzed matrix cross-linking in differentiating cartilage:
      identification of osteonectin as a major glutaminyl substrate.
AB  - The expression of tissue transglutaminase in skeletal tissues is strictly
      regulated and correlates with chondrocyte differentiation and cartilage
      calcification in endochondral bone formation and in maturation of tracheal
      cartilage (Aeschlimann, D., A. Wetterwald, H. Fleisch, and M. Paulsson. 1993. J.
      Cell Biol. 120:1461-1470). We now demonstrate the transglutaminase reaction
      product, the gamma-glutamyl-epsilon-lysine cross-link, in the matrix of
      hypertrophic cartilage using a novel cross-link specific antibody. Incorporation
      of the synthetic transglutaminase substrate monodansylcadaverine (amine donor) in
      cultured tracheal explants reveals enzyme activity in the pericellular matrix of
      hypertrophic chondrocytes in the central, calcifying areas of the horseshoe
      shaped cartilages. One predominant glutaminyl substrate (amine acceptor) in the
      chondrocyte matrix is osteonectin as revealed by incorporation of the dansyl
      label in culture. Indeed, nonreducible osteonectin-containing complexes of
      approximately 65, 90, and 175 kD can be extracted from mature tracheal cartilage.
      In vitro cross-linking of osteonectin by tissue transglutaminase gives similar
      products of approximately 90 and 175 kD, indicating that the complexes in
      cartilage represent osteonectin oligomers. The demonstration of extracellular
      transglutaminase activity in differentiating cartilage, i.e., cross-linking of
      osteonectin in situ, shows that tissue transglutaminase-catalyzed cross-linking
      is a physiological mechanism for cartilage matrix stabilization.

PMID- 7730417
TI  - Topological approach to drug design.
AB  - In this paper we demonstrated that by an adequate combination of different
      topological indices it is possible to select and design new active compounds in
      different therapeutical scopes, with a very high efficiency level. Particularly
      successful in the search of new "lead drugs", the results show the surprising
      ability of the topological methods to describe molecular structures.

PMID- 7730418
TI  - [Resection of hepatic metastases from non colorectal cancers. Our experience
      apropos of 20 cases].
AB  - The authors analyse their experience of 20 hepatic resections of metastatic
      malignant lesion to the liver from non-colorectal primary neoplasms: tubal or
      ovarian adenocarcinoma (3 cases), digestive adenocarcinoma (6 cases), sarcoma (3
      cases) and endocrine malignancies (8 cases). Then, they discuss the justification
      of such aggressive approach, the type of hepatic resection that has to be done
      and the date of the procedure according to the characteristics of the secondary
      neoplasm (synchronous or metachronous). The histological type of the primary
      malignancy is an important factor in this debate.

PMID- 7730419
TI  - [Accidents of chemotherapy involving the upper limb].
AB  - Subcutaneous extravation of antimitotic agents in the upper limb is a rare
      complication of chemotherapy. The functional integrity of the limb can be
      compromised due to severe skin damage. Extensive soft tissue necrosis is
      difficult to manage and cannot always be repaired without sequellae. Based on an
      analysis of a series of patients and a review of the literature, we report the
      main pathophysiological features and clinical signs of such accidents as well as
      the still debated therapeutic management. Two points are essential: the emergency
      situation created by these accidents requiring adequate and rapid treatment
      despite the apparently benign appearance of the extravation and imperative
      prevention which is the main therapeutic tool.

PMID- 7730420
TI  - [Facial motor lesion after surgery of the parotid gland].
AB  - The authors report a retrospective study of 351 parotidectomies observed during a
      28 years period. The average follow-up is 28 months. Preoperative and post
      operative facial nerve function, type of parotidectomy, surgical management of
      facial nerve and histologic diagnosis according to the revised WHO classification
      (1990) are presented. Type of parotidectomy and degree of tumor malignancy are
      statistically analyzed. It seems that occurrence of post-operative facial nerve
      dysfunction depends on radical parotidectomy, whereas long term dysfunction is
      determined by tumor malignancy. Malignant epithelial tumors of the major salivary
      glands proved to be radiosensitive. Apart from preoperative dysfunction, clinical
      involvement and impossible facial nerve dissection, the authors insist upon
      sparing the facial nerve, event in the case of microscopic residual tumors, and
      prefer postoperative radiotherapy.

PMID- 7730422
TI  - [Occlusions by colonic cancers: emergency treatment (62 cases)].
AB  - Sixty two patients (38 men, 24 women) were operated in emergency for colic
      occlusion from neoplasia. The mean age was 69.6 (+/- 12.71). Fourty four (70%)
      had an history of cardiovascular disease. Tumor resection has been possible in
      95% of cases. The mortality was 24.19% in the first two months postoperatively
      and 11% between the second and the fourth month. The morbidity was 32.2% and the
      mean length of stay in hospital was 22 days (+/- 16.6). The morbidity was less in
      case of right hemicolectomy (17.3 days) than for left colic resections (26 days).
      The postoperative mortality was not correlated to age but to lost of weight more
      than 10 kg (p < 0.0001) and to a mean central preoperative temperature more than
      37.5 degrees C (p < 0.002). Reducing the number of surgical procedures is
      beneficial in patients older than 70 years.

PMID- 7730421
TI  - [Amputation below the elbow made possible by emergency covering of the stump with
      a free parascapular flap].
AB  - The extent of the damage in a case of complex trauma of the upper limb required
      amputation. After debridment cleaning, there was not enough soft tissue to cover
      a stump below the elbow. The joint was saved by amputating below the elbow and
      covering during the same operation with a free parascapular flap.

PMID- 7730423
TI  - [Pyelo-ureteral dilatation revealing appendiceal abscess. Apropos of 2 cases].
AB  - The pyelo-ureteral dilatation revealing a appendiceal abscess is a uncommon
      situation. Its physio-pathological mechanism is not clear. The authors present
      two cases of which the diagnosis was not immediately made. The appendiceal
      abscess treatment is usually enough to make disappear the ureteral dilatation and
      the after effects stenosis are exceptional.

PMID- 7730424
TI  - [Hydatid cyst of the psoas].
AB  - Recurrent hydatic cyst of the psoas is an exceptional disease in France but
      should not be missed in patients coming from endemic areas. A case report and a
      review of the literature on the aetiopathology, diagnosis and therapy are
      presented. Abdominal pelvic CT scan should give the diagnosis. Surgical treatment
      is indicated, with complete exeresis to avoid early relapse.

PMID- 7730425
TI  - [Actinomycosis: value of percutaneous drainage of intra-abdominal abscesses].
AB  - Abdominal actinomycosis was localized in the liver with intra-abdominal
      abscesses. The disease had evolved for several years before diagnosis.
      Percutaneous interventional radiology allowed taking biopsies which confirmed the
      diagnosis. Percutaneous drainage of the intra-abdominal abscesses with
      antibiotherapy was successful without iterative surgery.

PMID- 7730426
TI  - [Intragastric foreign bodies. Apropos of an unusual case].
AB  - The following report describes a personal experience of an extremely rare case of
      sharp metal foreign bodies discovered in the stomach of a 22 year old adult
      African in good health. The authors underline the strange character of the case
      observed, not only because of the patient's perfect tolerance towards the foreign
      bodies, mainly sharp metal objects, but also considering the very large amount of
      objects found and it's corresponding weight (1 kg 400 g). Extraction of the
      foreign bodies was done by gastrotomy. Basing on our experience and following a
      review of the literature, the authors discuss the different problems which may
      occur due to the presence of foreign bodies in the gastrointestinal tract.

PMID- 7730427
TI  - [A case of isolated vaginal agenesis treated by inverted T-shaped peritoneal
      surgery].
AB  - A technique inspired by the Bloch-Tsirulnikov technique uses a double access for
      covering the neocavity with an inversed T peritoneal flap from the Douglas pouch.
      This technique was performed in one case with satisfactory functional results
      after 20 months follow-up.

PMID- 7730428
TI  - [Intrathyroid metastasis from cancer of the breast].

PMID- 7730429
TI  - [Acute occlusions of the aorta].
AB  - Acute occlusion of the aorta is a vascular emergency with high mortality, greater
      than 30% after revascularization, due to the extent of the ischaemic territory
      and the haemodynamic consequences. Over a period of 12 years, 34 patients (22
      males, 12 females) underwent surgery for acute occlusion of the aorta. Acute
      bilateral ischaemia was present in 24, unilateral ischaemia in 6 and sub-acute
      ischaemia in 4. An embolus of cardiac origin was the cause in 13 cases, disease
      of the aorta itself in 11 cases and hypercoagulability in 10 including 7 due to
      allergy to heparin. The delay from onset of ischaemia to revascularization was 9
      hours (mean). Revascularization was done by simple bifemoral embolectomy in 19
      cases, by aortobifemoral bypass in 9 and by extra-anatomic bypass in 6 (3 supra
      pubic, 3 axillo-bifemoral). Six patients (18%) died during the post-operative
      period. Delay to care had been greater than 12 hours in most of these patients.
      One or more post-operative complications occurred in 18 patients (53 p. 100)
      including repeated thrombosis, insufficient revascularization, ischaemic
      neuropathy. Long-term survival at 3 years was 30%. Prognosis might be improved by
      three elements: reducing the duration of ischaemia by rapid diagnosis and
      emergency revascularization, better control of metabolic disorders, screening for
      heparin allergy before thrombotic events occur.

PMID- 7730430
TI  - Evaluation of an agglutination HIV-1 + 2 antibody assay.
AB  - Studies have shown that an HIV (HIV-PA) agglutination assay (Serodia) for the
      detection of antibody to human immunodeficiency virus (HIV) can be as sensitive
      and as specific as enzyme-linked immunosorbent assay (ELISA). However, since this
      HIV assay was designed to detect antibody to the HIV-1 virus, a substantial
      number of HIV-2 positive sera are missed by this assay. Since the HIV-2 has now
      been found throughout the world this test is becoming less suitable. The new HIV
      1 + 2 assay version (HIV-1 + 2 PA) was evaluated in 300 sera, which contained 50
      HIV-1, 40 HIV-2 and 10 HIV-1/HIV-2 antibody positive samples, and a sensitivity
      and specificity of 100% and 99%, respectively, was obtained. Whereas all HIV-2
      positive sera were detected by the new HIV-1 + 2 version, 26% (13/50) were missed
      by the old version of the agglutination test. It is concluded that the HIV-1 + 2
      PA assay is a promising instrument free assay which can be used for screening
      purposes in areas where both HIV-1 and HIV-2 are present.

PMID- 7730431
TI  - Use of juvenile hormone esterase as a novel reporter enzyme in the baculovirus
      expression system.
AB  - Juvenile hormone esterase (JHE) has a number of characteristics favorable for use
      as a reporter enzyme. It is extremely stable under a variety of adverse
      conditions including in organic solvent. JHE is easily detected by a rapid and
      sensitive colorimetric assay, and detection is facilitated by export of the
      enzyme from the cell. Its use is illustrated in the baculovirus expression system
      by promoter studies and evaluation of culture conditions necessary for optimal
      production of recombinant proteins. From this, it was found that protein yields
      were greater for Autographa californica nuclear polyhedrosis virus (AcNPV)
      expression vectors using the basic protein promoter to drive production of JHE
      than for the p10 protein or polyhedrin promoters. This has significant
      implications for current baculovirus expression methodologies. The effect of
      multiplicity of infection on protein yield was found to be insignificant between
      0.1 and 10 for expression under the basic protein promoter. Yields of JHE were
      about 40% higher from the cell line Tn5B1-4 ('High Five') relative to the Sf21
      cell line under optimized conditions for each cell line, with maximum yields
      obtained at 2-3 days, and 3-5 days post-infection for the two cell lines
      respectively when cultured in ExCell 401 medium. The presence of fetal calf serum
      in the cell culture medium enhanced protein yields from both cell lines. These
      studies demonstrate the use of JHE as a reporter enzyme for optimizing high
      yields of protein from the baculovirus expression system. JHE also has a
      potential application as a reporter enzyme in other eukaryotic systems. The
      advantages and use of JHE over other reporter enzyme are discussed.

PMID- 7730432
TI  - Detection and typing of human papillomavirus by single hybridization.
AB  - A rapid and non-radioactive molecular hybridization test was developed which
      simultaneously detects and types different human papillomaviruses (HPV) DNA in
      fresh and paraffin-embedded clinical specimens. The method includes reverse blot
      hybridization between different recombinant HPV plasmids immobilized on nylon
      membrane and probe of cellular DNA amplified and biotin- or digoxigenin-labeled
      by the polymerase chain reaction (PCR). PCR protocol using consensus primers
      includes the mixing of Taq polymerase at high temperature (Hot-Start) and the
      addition of the hapten-conjugated nucleotide after the first ten cycles of
      amplification. The sensitivity level of this method resulted in detecting about
      50 copies of HPV 16 for sample, independently of hapten used. The specificity of
      the typing method was also validated by more laborious and conventional analyses
      such as Southern-blot or PCR followed by several hybridizations with specific
      probes. Using this test HPV-11, -16, -18, -31 and -35 were typed in a number of
      samples from patients attending hospital. The method appears suitable for the
      handling of clinical samples in a selected population screening for type specific
      infections by HPV.

PMID- 7730433
TI  - Comparative study of a blocking enzyme-linked immunosorbent assay and the
      immunoperoxidase monolayer assay for the detection of antibodies to the porcine
      reproductive and respiratory syndrome virus in pigs.
AB  - A blocking enzyme-linked immunosorbent assay (ELISA) for detecting antibodies to
      the porcine reproductive and respiratory syndrome virus (PRRSV) in pig sera was
      developed and compared with the immunoperoxidase monolayer assay (IPMA), the most
      widely used serological diagnostic test in Europe. The blocking ELISA was
      specific and more sensitive than the IPMA when applied to field sera and to sera
      which were collected early after an experimental infection with PRRSV. Problems
      with high background activity as observed in IPMA or indirect ELISA were not
      encountered.

PMID- 7730434
TI  - Identification of HTLV-I- or HTLV-II-producing cells by cocultivation with BHK-21
      cells stably transfected with a LTR-lacZ gene construct.
AB  - The Syrian Hamster kidney cell line (BHK-21) was stably transfected with a
      plasmid vector containing the lacZ bacterial gene under the control of a HTLV-I
      LTR promoter. In these cells termed pA18G-BHK-21, this lacZ construct is
      inducible by the tax protein produced by a tax expression vector. It was also
      shown that beta-galactosidase synthesis was detected within 48 h after
      cocultivation of pA18G-BHK-21 cells with HTLV-I (HUT-102, MT2, C91/PL, 2060) or
      HTLV-II (MoT strain) -producing cells. The number of positive cells was directly
      related to the number of HTLV-I or -II-infected cells seeded. In addition, the
      LTR transactivation observed in coculture with HTLV-I-infected cells was
      specifically inhibited by sera containing antibodies directed against HTLV-I
      proteins, but not, or only weakly, by sera containing HTLV-II antibodies.
      Conversely, beta-galactosidase expression induced by HTLV-II-infected cells was
      inhibited by sera of HTLV-II-infected individuals, but not, or only weakly, by
      HTLV-I-positive sera. Irrespective of the inducer cell, sera from uninfected
      people did not inhibit LTR-driven expression of the lacZ gene in pA18G-BHK-21
      cells cocultivated with HTLV-producing cells. This assay may thus be employed
      profitably for the detection and quantification of both HTLV-producing cells and
      HTLV-specific antibodies.

PMID- 7730435
TI  - A liquid-phase blocking ELISA for the detection of antibodies to rabies virus.
AB  - A liquid-phase blocking ELISA was adapted to the detection and titration of
      antibodies to principally the nucleoprotein of rabies virus. Sera from animals
      that had either been vaccinated against rabies or inoculated with street rabies
      viruses, as well as sera from animals that had no recorded contact with rabies,
      were tested. These included sera from people, cattle, sheep, goats, dogs,
      laboratory mice, rabbits, yellow mongooses, wild dogs and lions. Where possible,
      the results were compared with those obtained with a commercial kit incorporating
      an indirect ELISA that measures antibody to the rabies glycoprotein. There was a
      high correlation (r = 0.79) between the two tests. The blocking ELISA provides a
      single test suitable for the rapid detection of antibodies against rabies virus
      in the sera of any animal species and for that reason is particularly apt for
      epidemiological investigations in regions where species diversity is important,
      as in southern Africa.

PMID- 7730436
TI  - Rapid and effective detection of mutations in the p53 gene using nonradioactive
      single-strand conformation polymorphism (SSCP) technique applied on PhastSystem.
AB  - The polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP)
      method is a powerful tool for the screening of genetic alterations, including
      single-base substitutions. In the present study, the conventional SSCP technique
      was modified on the semiautomated electrophoresis system (PhastSystem) for the
      detection of mutations in the p53 tumor suppressor gene. The SSCP running
      conditions were optimized for three PCR-amplified DNA fragments, spanning exons 5
      through 9 of the p53 gene, using the PCR-products derived from the CaSki and
      HaCaT cells as the normal and mutant controls, respectively. The optimized SSCP
      protocols were tested on nine human vulvar and vaginal carcinoma-derived cell
      lines. The optimizing experiments indicated that the running temperature and gel
      density can affect significantly the electrophoretic mobility and resolution of
      single-stranded DNA molecules. Because the gel temperature is the most important
      parameter affecting the conformation and thus electrophoretic mobility of single
      strands, one of the most important advantages of the SSCP technique on the
      PhastSystem is that the running temperature is controlled precisely. In addition
      to the fast electrophoretic separation, the PhastSystem also offers the use of a
      silver staining method allowing direct visualization of DNA with high detection
      sensitivity. Thus, the important advantage of this modified SSCP technique is the
      short time required for analysis, including electrophoresis and DNA detection. It
      is concluded that the SSCP method applied on the PhastSystem has the advantages
      of simplicity, efficiency, speed and reproducibility, and is suitable for
      clinical diagnostic purposes.

PMID- 7730437
TI  - Monitoring the cDNA synthesis of dengue-2 virus by RT PCR.
AB  - Reverse transcriptase polymerase chain reaction (RT PCR) was utilized to observe
      the complementary DNA (cDNA) synthesis from the 10723 base dengue-2 virus
      template by in vitro reverse transcription. The PCR product amplified from 5'-end
      of the genome (PCR primers N1A-E1) indicates the completeness of the cDNA
      synthesis because the cDNA primer D8B was located at 3'-end and the cDNA
      synthesized encompassed the entire RNA template. The integrity of the dengue
      virus RNA was also determined by the cDNA primer extension from 3'-end and the
      PCR amplification at various regions from 5'-end of the RNA template. In
      conclusion, RT PCR could be applied to monitor cDNA synthesis by in vitro reverse
      transcription and measure the integrity of viral RNA template. Moreover, it is
      demonstrated that at least 10.7 kilobases of the cDNA could be synthesized from
      dengue-2 virus RNA by in vitro reverse transcription.

PMID- 7730438
TI  - Demonstration of the presence of protease-cutting site in the spacer of hepatitis
      B viral Pol protein.
AB  - Molecular genetic studies have revealed that the human hepatitis B viral (HBV)
      Pol protein, a polypeptide of about 94 kDa, contains four domains. These are the
      5'-terminal protein, spacer, RNA reverse transcriptase/DNA polymerase, and RNase
      H, respectively, from the amino (N) to carboxy (C) terminus. No evidence
      indicates as yet the involvement of a specific protease in cleaving the Pol
      protein or the presence of protease-cutting sites in the Pol protein. An in vitro
      translated Pol protein was shown to be cleaved by purified thrombin but not in
      the presence of its inhibitor, hirudin. Two thrombin-cutting sites, spanning 194
      amino acids, were then deduced by thrombin digestion of Pol protein with various
      lengths of C-terminal deletion. These two putative cutting sites, one located in
      the spacer region and the other in the beginning of the polymerase region, were
      found to be conserved at similar positions in the Pol protein of all
      hepadnaviruses. By using a novel method called the LacZ localization assay (LLA),
      it was demonstrated that a tripartite fusion protein containing the nucleus
      localization sequence (NLS) of SV40 large T Ag, the putative thrombin cutting
      sequence (Ile-Arg-Ile-Pro-Arg320-Thr) of HBV Pol protein and the full length beta
      galactosidase of E. coli, exhibited a lower percentage (approximately 53%) of
      targeting into the nucleus of transfected hepatoma cells when compared with a
      similar tripartite protein containing a single mutation (Arg320 residue into
      Trp320) of HBV Pol protein (approximately 78%) or with a bipartite protein of
      SV40 NLS-beta-galactosidase (approximately 90%). These results indicate that the
      putative thrombin-cutting site in the spacer region of HBV Pol protein could be
      cleaved by a cellular protease resulting in the separation of NLS sequence from
      the beta-galactosidase and rendering a lower frequency of X-gal staining in the
      nucleus.

PMID- 7730439
TI  - Optimisation and evaluation of a quantitative chemiluminescent polymerase chain
      reaction assay for hepatitis C virus RNA.
AB  - A quantitative non-isotopic assay for measuring hepatitis C virus (HCV) RNA has
      been developed and evaluated. Viral RNA extracted from serum is reverse
      transcribed and amplified by the polymerase chain reaction (PCR) using
      biotinylated 5' non-coding region primers. PCR products are captured on
      streptavidin coated microtitre plates, denatured with sodium hydroxide and
      hybridised with an alkaline phosphatase-labelled oligonucleotide probe.
      Quantification is achieved by measuring the intensity of light emitted by a
      dioxetane-based chemiluminescent substrate. The chief advantages of the assay
      are: (i) extreme sensitivity with the ability to detect single molecules of HCV
      cDNA, (ii) a 5 log10 dynamic range sufficient to cover the 10(3)-10(8) genomes/ml
      viraemia levels typically seen in patient samples, (iii) specificity and
      reproducibility suitable for application in a clinical context, and (iv) a rapid
      non-nested assay format with the ability to handle large throughputs and with a
      potential for automation. The feasibility of using the assay to monitor viraemia
      level changes in patients undergoing interferon therapy for chronic HCV infection
      has been demonstrated.

PMID- 7730440
TI  - Optimization of an in situ hybridization technique for the detection of foot-and
      mouth disease virus in bovine tissues using the digoxigenin system.
AB  - An in situ hybridization technique has been optimised for use on paraffin
      embedded sections of tissues collected from cattle infected experimentally with
      foot-and-mouth disease virus type O1BFS. Tissue was collected 5 days after
      infection by direct contact. In situ hybridization was carried out using an RNA
      probe corresponding to a region of the 3D gene which codes for the RNA
      polymerase, and labelled with digoxigenin. Consistent, reproducible signal was
      detected within the epithelial layers of the palatine tonsil, soft palate and
      pharyngeal tissue studied. This is the first time that a digoxigenin-based system
      has been used successfully for FMD virus RNA detection with bovine tissue
      samples.

PMID- 7730441
TI  - Typing human T-cell lymphotropic virus (HTLV-I and HTLV-II) by nested polymerase
      chain reaction: application to clinical specimens.
AB  - Human T-cell lymphotropic virus type I and II provirus DNA was detected by
      polymerase chain reaction (PCR). MT-2 (HTLV-I infected), C3/44 Mo (HTLV-II
      infected) cell lines and peripheral blood mononuclear cells (PBMNC) from HTLV
      seropositive samples were used. The procedure consists of first amplification
      which detects both HTLV-I and HTLV-II, and a second amplification (nested-PCR) to
      discriminate between the two viruses and to improve sensitivity. Optimal
      conditions of MgCl2 concentration and annealing temperature were found for
      maximal amplification and specificity. This method was used for the amplification
      of conserved regions of pol and env genes. 1.5 pg of MT-2 and 5 pg of C3/44 Mo
      cell line DNAs were detected using nested-PCR and liquid hybridization in the pol
      system. The env system could detect 1.5 pg of MT-2 and 1.5 pg of C3/44 Mo cell
      lines DNAs using nested-PCR and liquid hybridization. The pol system can type
      both HTLV-I and HTLV-II in only two steps without the use of type-specific
      radiolabeled probes. Furthermore, this method can detect and discriminate the two
      viruses in one step PCR using the primers used in the nested-PCR. Nevertheless,
      there is a decrease in sensitivity of 100-fold. The results of five seropositive
      samples confirmed by Western blot are compared with PCR. PCR typed one of these
      samples as HTLV-I and the rest as HTLV-II. This technique is useful in cases such
      as window period, perinatal studies and when serologic results are not
      satisfactory.

PMID- 7730442
TI  - An antigen trapping ELISA for the detection of capripoxvirus in tissue culture
      supernatant and biopsy samples.
AB  - A trapping ELISA for the detection of capripoxvirus antigen in tissue culture
      supernatant and biopsy material was developed, using a guinea-pig polyclonal
      detector antiserum raised against a recombinant capripoxvirus specific antigen,
      expressed in Escherichia coli using the plasmid vector pGEX-2T. The ELISA
      detected antigen in tissue culture samples that on virus titration contained
      equal to or in excess of 10(2.8) TCID50/ml. Virus isolation and ELISA were
      compared for the detection of capripoxvirus in skin biopsy samples from sheep,
      goats and cattle. The ELISA compared well with virus isolation, and has
      applications as a diagnostic test. This assay reduces the reliance of diagnostic
      laboratories on tissue culture facilities, and can be used to confirm the
      presence of capripoxvirus in tissue culture.

PMID- 7730443
TI  - A monoclonal antibody to alpha 4 integrin suppresses and reverses active
      experimental allergic encephalomyelitis.
AB  - In experimental allergic encephalomyelitis (EAE), circulating leukocytes enter
      the central nervous system (CNS) producing inflammation, myelin damage and
      paralysis. Prevention of leukocyte infiltration by an antibody against alpha 4
      integrin suppressed clinical and pathological features of EAE in the guinea pig.
      Rapid clearance of leukocytes from the CNS and reversal of clinical findings were
      observed when anti-alpha 4 treatment was administered during active disease.
      Clinical improvement was accompanied by a marked decrease in abnormal
      pathological findings, including demyelination. Therefore anti-alpha 4 is an
      effective treatment of EAE and may be similarly useful in the treatment of
      autoimmune diseases such as multiple sclerosis.

PMID- 7730444
TI  - Clusterin expression by astrocytes is influenced by transforming growth factor
      beta 1 and heterotypic cell interactions.
AB  - This study characterizes the effect of transforming growth factor (TGF) beta 1 on
      clusterin expression in rat brain cells. 24 h after an acute unilateral
      intracerebroventricular infusion of TGF-beta 1, clusterin mRNA prevalence was
      increased in astrocytes that contained immunoreactive (IR) glial fibrillary
      acidic protein (GFAP). TGF-beta 1 selectively induced clusterin mRNA in
      astrocytes, as no clusterin mRNA was detected in neurons, oligodendrocytes, or
      microglia. TGF-beta 1 induced a bilateral increase in clusterin mRNA per
      astrocyte. Astrocyte hypertrophy (GFAP-IR area) was only increased on the
      ipsilateral side. In pure astrocyte cultures, TGF-beta 1 (200 pM) decreased
      clusterin mRNA levels and the rate of clusterin RNA transcription. However, in
      cultures of astrocytes that contained microglia and oligodendrocytes (mixed glia
      cultures), TGF-beta 1 caused a dose-dependent increase in astrocytic clusterin
      mRNA levels. The astrocytes that responded to TGF-beta 1 included two GFAP-IR
      subtypes, type 1 and 2. TGF-beta 1 increased clusterin protein in the conditioned
      medium from cultured glia, in either monotypic or mixed glial cultures. Thus, TGF
      beta 1 and heterotypic cell interactions influence clusterin expression by
      astrocytes and may be important to the role of clusterin in multiple sclerosis,
      AIDS, and Alzheimer's disease.

PMID- 7730445
TI  - T lymphocyte infiltration in the brain following anterior chamber inoculation of
      HSV-1.
AB  - Following inoculation of the KOS strain of herpes simplex virus type 1 (HSV-1)
      into one anterior chamber of euthymic BALB/c mice, virus spreads from the
      injected eye to the central nervous system and from the central nervous system to
      the optic nerve and retina of only the uninoculated eye. In contrast, in athymic
      BALB/c mice or mice depleted of both CD4+ and CD8+ T cells, virus spreads to the
      optic nerve and retina of both the injected eye and the uninjected eye. To
      determine the location in the central nervous system where spread of virus to the
      optic nerve and retina of the injected eye is prevented, euthymic BALB/c mice
      were injected with a mixture of KOS and RH116, a mutant of KOS that contains the
      Escherichia coli beta-galactosidase (beta-gal) gene. Several animals were
      sacrificed each day; serial frozen sections of the brain were prepared and
      sequential sections were stained for beta-gal or for T cells. At all sites except
      the suprachiasmatic nuclei, virus and T cells arrived at approximately the same
      time. However, at day 5 post inoculation (PI), T cells were present in both the
      ipsilateral and the contralateral suprachiasmatic nuclei, but only the
      ipsilateral suprachiasmatic nucleus was virus-positive. Since virus spreads from
      the ipsilateral suprachiasmatic nucleus to the contralateral optic nerve, these
      results suggest that T cells infiltrating the area of the contralateral
      suprachiasmatic nucleus prior to the arrival of virus at this site prevent virus
      spread into the optic nerve of the inoculated eye.

PMID- 7730446
TI  - Role of nitric oxide and melanogenesis in the accomplishment of anticryptococcal
      activity by the BV-2 microglial cell line.
AB  - In the present paper, we investigated the involvement of cryptococcal
      melanogenesis and macrophage nitric oxide (NO) production in the accomplishment
      of anticryptococcal activity by microglial effector cells, using the murine cell
      line BV-2. We demonstrate that the constitutive levels of anticryptococcal
      activity exerted by BV-2 cells is significantly enhanced upon interferon gamma
      plus lipopolysaccharide treatment. The phenomenon, which occurs with no
      enhancement of phagocytic activity, is associated with the production of high
      levels of NO and is abolished by addition of NG-monomethyl-L-arginine. Comparable
      patterns of results are observed employing either unopsonized or opsonized
      microbial targets, the latter microorganisms being markedly more susceptible to
      BV-2 cell antimicrobial activity. Furthermore, melanization of Cryptococcus
      neoformans significantly reduces its susceptibility to BV-2 antimicrobial
      activity, regardless of the fact that activated macrophages or opsonized
      microorganisms have been employed. In conclusion, our results provide evidence
      that NO-dependent events are involved in the fulfillment of anticryptococcal
      activity by activated microglial cells and that fungal melanization is a precious
      escamotage through which C. neoformans overcomes host defenses.

PMID- 7730447
TI  - IVth Congress of the International Society of Neuroimmunology Amsterdam, The
      Netherlands, 23-27 October 1994.

PMID- 7730448
TI  - Increased frequencies of HPRT mutant T lymphocytes in patients with Guillain
      Barre syndrome and chronic inflammatory demyelinating polyneuropathy: further
      evidence for a role of T cells in the etiopathogenesis of peripheral
      demyelinating diseases.
AB  - We have used the HPRT mutant clonal assay to determine the frequency of mutant T
      lymphocytes (FMC), as a measure of recent T cell stimulation, in the blood of
      patients with Guillain-Barre syndrome (GBS) and chronic inflammatory
      demyelinating polyneuropathy (CIDP). We found that, compared to healthy controls,
      the FMC in patients with GBS (16) and CIDP (10) was significantly increased in
      the progressive phase of the neuropathy. FMC returned to normal values during
      recovery, suggesting a relationship between FMC and disease activity. No
      correlation was found between FMC values and motor deficit or severity of the
      neuropathy. The FMC of the GBS patients with a history of infection before onset
      of neurological symptoms or with insufficient respiration was not significantly
      different from the other GBS patients. Immunophenotypic analysis showed that the
      fraction of CD8+ HPRT mutant T cell clones was significantly increased in GBS
      patients (48%) compared to healthy controls (3%) or CIDP patients (4.5%). Our
      results are compatible with the notion that T cells are involved in the
      pathogenesis of demyelinating inflammatory neuropathies.

PMID- 7730449
TI  - IgG anti-GM1 antibodies from patients with acute motor neuropathy are
      predominantly of the IgG1 and IgG3 subclasses.
AB  - Increased titers of IgG anti-GM1 and anti-asialo GM1 (GA1) ganglioside antibodies
      are present in some patients with the Guillain-Barre syndrome, particularly with
      the motor axonal variant, and following infection with Campylobacter jejuni or
      parenteral administration of gangliosides. The subclass distribution of IgG anti
      GM1 or GA1 antibodies from 19 patients with acute motor neuropathy and elevated
      antibody titers were measured by ELISA using mouse monoclonal antibodies specific
      for human IgG subclasses. The anti-GM1 or GA1 antibodies were predominantly of
      the IgG1 and IgG3 subclasses, which are capable of complement fixation, and are
      characteristic of a T cell-dependent antibody response.

PMID- 7730450
TI  - Strain differences in sleep and other pathophysiological sequelae of influenza
      virus infection in naive and immunized mice.
AB  - To characterize behavioral and physiological alterations induced by viral
      respiratory infection, C57BL/6 and BALB/c strains of mice were monitored for 2
      days before and 4 days after intranasal inoculation with influenza virus. Both
      strains developed hypothermia, decrease locomotor activity, and decreased delta
      wave amplitude during sleep within 24 h after inoculation. However, infected
      C57BL/6 mice also spent more time in slow-wave sleep, but infected BALB/c mice
      did not. The increased SWS in C57BL/6 mice occurred during the lights-off phase
      of the circadian cycle, and resulted in loss of the normal circadian rhythmicity
      of sleep. Increased sleep also occurred after viral challenge of immunized
      C57BL/6 mice, but was not observed after secondary challenge of immunized BALB/c
      mice. These data indicate that sleep alterations may accompany viral infections
      in some, but not all, strains of mice. The dissimilar sleep patterns seen in
      C57BL/6 and BALB/c mice after influenza infection may reflect differences in
      their immune response to influenza virus.

PMID- 7730451
TI  - A prospective study of ponderosity, body image, self-concept, and psychological
      variables in children.
AB  - The association between changes in body mass index over 1 year and measures of
      psychological functioning was evaluated in 314 boys and 253 girls with a mean age
      of 9 years. Anthropometric evaluations and standardized surveys were administered
      to students in all four-grade classes of seven suburban schools in the fall of
      two consecutive school years. Increases in body mass index were significantly
      associated with unfavorable changes in physical activity attitudes, activity
      preferences, perceived physical activity competence, self-concept, and body
      image. There was limited support for a hypothesis that overweight children are
      more sensitive to changes in body shape than non-overweight children. The finding
      of negative psychological consequences associated with increases in body mass
      index among children suggests that children may be overconcerned with body weight
      and shape.

PMID- 7730452
TI  - Social and personal factors in marijuana use and intentions to use drugs among
      inner city minority youth.
AB  - Limited information is available about the etiology of illicit drug use among
      minority youth. This study examined predictors of marijuana use and intentions to
      use marijuana, cocaine/crack, and other drugs for African-American and Hispanic
      seventh graders (N = 757). Self-reports of marijuana use and intentions to use
      drugs were collected along with data concerning background, social environmental,
      and individual characteristics hypothesized to be related to drug use. Results
      indicated that social influences, including adults, friends, and the most admired
      person's marijuana use, predicted marijuana use. Individual characteristics, such
      as a lack of knowledge about the prevalence and negative social consequences of
      marijuana use, positive attitudes toward marijuana use, and inadequate social,
      communication, and refusal skills increased suspectability to marijuana use. Lack
      of self-efficacy was related to intentions to use cocaine and other drugs.
      Implications of these findings are discussed with respect to the development of
      effective prevention programs.

PMID- 7730453
TI  - Early intervention with Portuguese mothers: a 2-year follow-up.
AB  - Results of a 2-year follow-up after an early intervention with low-middle-class
      primiparous Portuguese mothers are presented. On the 3rd day of their infants'
      lives, 40 mothers underwent a structured intervention using selected items of the
      Brazelton Neonatal Behavioral Assessment Scale. An additional 20 mothers
      randomized to the control group had a talk with a pediatrician about general
      problems of infant health care. On Day 28, the "sensory orientation" and
      "cuddliness" competencies of the infants in the experimental group were
      significantly enhanced when compared with the same competencies among the infants
      in the control group. In addition, dyads in the experimental group had
      established a more favorable pattern of interaction, particularly after short
      stressful situations (these situations included short separations from the mother
      in which a stranger was present, short separations in which no one was present,
      and a stillface situation). Short-term effects (the first month of life) were
      particularly noticeable, especially in terms of the babies' neurobehavioral
      development and mother-infant interaction. Long-term effects (3, 6, 9, 12, 15,
      18, and 24 months), though less clear, were evident in the form of better
      interactive patterns among the dyads in the experimental group. This was
      particularly evident after the stressful situations to which they were submitted.
      These results are discussed in terms of both their scope and their clinical
      impact.

PMID- 7730454
TI  - Cocaine-exposed children: follow-up through 30 months.
AB  - This prospective, blinded study evaluates the effect of in utero cocaine exposure
      on outcome of nonasphyxiated, term and near-term children born to women of low
      socioeconomic status. Two hundred nineteen children (101 cocaine-exposed and 118
      control) with extensive natal evaluations are evaluated at 6-month intervals. We
      report here growth, performance on the Bayley Scales of Infant Development (BSID)
      through 30 months of age, and tone and reflexes at 6 and 12 months. To date,
      subjects have had 816 follow-up visits, with subject retention greater than or
      equal to 73%. Cocaine-exposed children showed statistically lower mean weights
      and smaller mean head circumferences than control children over the 30-month
      follow-up period (p < or = .011). The percentage of children with abnormal tone
      and reflexes, however, was similar in the two groups at 6 and 12 months (p > or =
      .34). Mean BSID Mental Development Index (MDI) and Psychomotor Development Index
      scores did not differ between the two groups (p > or = .16), although both
      groups' scores decreased over time (p < .001). Of concern, both cocaine-exposed
      and control groups had lower mean MDI scores than those published for a group of
      children of higher socioeconomic status. We conclude that, in our cohort of
      children, low socioeconomic or minority status may have had a substantial
      influence on BSID scores whereas in utero drug exposure did not.

PMID- 7730455
TI  - Biosocial factors in early infancy as predictors of competence in adolescents who
      were born prematurely.
AB  - In a prospective longitudinal study of a cohort of 105 subjects born prematurely,
      competence was assessed from infancy through late adolescence. A biosocial model
      guided the research. Neonatal neurobehavioral organization (a composite of term
      visual attention, amount of time in active sleep, and 407 EEG pattern) and early
      social stimulation (the amount of talking the mother addressed to the infant
      during a home observation when the infant was 1 month old) in conjunction with
      social class were used to predict competence at key age periods through late
      adolescence. Intellectual competence, school achievement, social competence, and
      self perception of cognitive competence were studied. The results indicate that
      measures taken in the early infancy period were predictive of later competence,
      particularly intellectual competence, above and beyond social class. Twenty-eight
      percent of the variance in 18-year IQ scores was explained by the predictor
      variables. The study highlights the importance of directing efforts to improve
      the social environment of both the infant and the family.

PMID- 7730456
TI  - Families who somatize.
AB  - This investigation extends a previous study of children of people with
      somatization disorder and children of less severely affected somatizers. We used
      the revised Diagnostic Interview for Children and Adolescents, revised, and
      abstracted medical records to compare families in which a child as well as a
      parent had unexplained somatic complaints; we also identified parental predictors
      of children's somatization. Children in families with somatizing children had
      more emergency room use, more suicidal behavior, and more disability. Children in
      families of somatization disorder adults had 11.7 times as many emergency room
      visits as less severely affected somatizers and missed 8.8 times as much school.
      Parental somatization, substance abuse, and antisocial symptoms predicted
      children's somatization. Physicians in primary care should be aware of the
      frequency with which somatization occurs in other members of a family when it is
      identified in one member.

PMID- 7730457
TI  - The vulnerable child syndrome revisited.
AB  - Dimensions of the vulnerable child syndrome are clarified in a critical review of
      the research and clinical literature. The central construct of the vulnerable
      child syndrome, an increased parental perception of child vulnerability to
      illness or injury, is examined in the context of separation and loss. Measures of
      perceived child vulnerability are reviewed. A new conceptual model of parental
      perception of child vulnerability is presented that takes into account child,
      parent, parent-child, parent-clinician, and family factors. Directions for future
      research are suggested.

PMID- 7730458
TI  - The problem of matching.

PMID- 7730459
TI  - Biobehavioral comparisons between adopted and nonadopted rhesus monkey infants.
AB  - Differences between adopted and nonadopted infant rhesus monkeys were examined,
      as were differences between biological and foster mothers, in measures of infancy
      and postinfancy behaviors, maternal-infant interactions, and neuroendocrine and
      behavioral responses to separations. Newborns were experimentally allocated to
      continuous postnatal care by either their biological mothers (n = 9) or adoptive,
      nonbiological mothers (n = 7). Behavioral observations were completed during the
      neonatal period, during separations at 30 days and 5 months, and from 6 to 18
      months of age, when animals were housed in a large social group. Maternal and
      infant responses to separation stress were assessed using measures of behavioral,
      adrenocortical, and growth hormone reactivity. Out of 84 possible comparisons,
      only six achieved statistical significance, a number compatible with the
      operation of chance. Negligible differences in behavioral and neuroendocrine
      endpoints were found between adopted and nonadopted mother-infant pairs. These
      findings lend additional credence to human studies finding no increase in the
      incidence or severity of mental disorders in adopted children.

PMID- 7730460
TI  - Multiplane transesophageal echocardiographic evaluation of transvenous
      defibrillation leads.
AB  - Permanent transvenous cardioverter-defibrillator leads were investigated by
      multiplane transesophageal echocardiography (TEE) (1) to determine whether
      intracardiac lead segments can be visualized, (2) to verify the position of the
      coils, and (3) to detect possible thrombus formation. The diagnostic information
      obtained in 62 patients by TEE was compared to that of transthoracic
      echocardiography (TTE). Abnormal findings were only visualized by multiplane TEE.
      However, further controlled studies are needed to determine the clinical
      relevance of displaced caval (one patient) and ventricular coils (15 patients),
      ventricular (1 patient) or atrial (6 patients) loops, and of clinically
      uneventful thrombi (13 patients).

PMID- 7730461
TI  - Role of transvaginal sonography in the detection of endometriomata.
AB  - Endometriosis is a common cause of pelvic pain and infertility in young women.
      Transvaginal sonography is major means for diagnosing ovarian In our study, we
      scanned 60 patients with endometriomata who underwent laparotomy or laparoscopy.
      We compared preoperative ultrasonographic diagnosis with histological reports.
      The sonographic criteria for the diagnosis of endometriomata were (1) cystic
      structure with low, homogeneous echogenicity and (2) thick cystic wall with
      regular margins. In 50 patients, sonography suggested an endometrioma. In 47
      cases, the diagnosis was correct. The false-positive cases were all caused by
      cystic teratomas with a homogeneous sonographic pattern. Ten false-negative cases
      were diagnosed by ultra-sonography as functional ovarian cysts (5), teratomas
      (3), and benign ovarian cystoma (1). Only 1 case of a 5-mm endometrioma was
      demonstrated by laparoscopy but not by TVS. The sensitivity of TVS for diagnosing
      endometriomata was 82.4% and specificity 97.7%; the positive and negative
      predictive values were 94% and 92.8%, respectively. The diagnostic accuracy of
      TVS was 93%. In our experience, TVS is a very specific means for diagnosing
      endometriomata when the typical pattern is detected; however, the sensitivity of
      the technique needs to be improved.

PMID- 7730462
TI  - Further observations on the usefulness of the sonographic Murphy sign in the
      evaluation of suspected acute cholecystitis.
AB  - A positive sonographic Murphy sign, the presence of maximal tenderness elicited
      over a sonographically localized gallbladder, has been reported to be a helpful
      adjunctive finding in patients with proven acute cholecystitis who are evaluated
      with ultrasonography. We evaluated 200 patients with right upper quadrant pain,
      thought to be acute cholecystitis. Results of ultrasound examinations and
      subsequent follow-up were tabulated. The sensitivity of the sonographic Murphy
      sign in acute cholecystitis was 86% with a specificity of 35%, positive
      predictive value of 43%, and negative predictive value of 82%. The sensitivity of
      the sonographic findings, including stones, gallbladder wall edema, and
      pericholecystic fluid collections, was 93%, a specificity of 53%. The combination
      of the Murphy sign accompanied by gallstones yielded a specificity of 77%. The
      large number of false positives, and only moderate improvement in specificity
      when accompanied by gallstones, makes this sign unreliable in separating acute
      from chronic cholecystitis.

PMID- 7730463
TI  - Staging of hilar cholangiocarcinoma with ultrasound.
AB  - The preoperative assessment of the extent of biliary and vascular involvement by
      hilar cholangiocarcinoma is clinically important because resectability may be
      limited by tumor extension along the bile ducts into the hepatic parenchyma or to
      the adjacent hilar vessels. Thirty-five patients with hilar cholangiocarcinoma
      were studied with ultrasound, and the results were compared with operative
      findings and other diagnostic modalities. The level of intrahepatic biliary
      obstruction was determined in 100% of patients with ductal ectasia, and a tumor
      mass was shown in 37.1%. Imaging and Doppler ultrasound proved accurate in
      detecting the neoplastic involvement of the portal vein. Both correctly diagnosed
      portal occlusion and wall infiltration in 4 of 4 and 15 of 18 (83%) patients,
      respectively, without any false-positives. On the contrary, imaging ultrasound
      had poor sensitivity in detecting infiltration of the hepatic artery (43%) and
      metastases in regional lymph nodes (37%), liver (66%), and peritoneum (33%). In
      conclusion, ultrasound may be valuable in the preoperative staging of hilar
      cholangiocarcinoma, specially in predicting ductal and portal involvement.

PMID- 7730464
TI  - Thyroid nodules: re-evaluation with ultrasound.
AB  - The purpose of this study was to clarify ultrasound (US) evaluation of
      microcalcifications and determine whether the calcifications seen in US scans can
      reliably predict malignant thyroid tumors. Diagnostic accuracy of
      microcalcification and other various signs seen in US scans for predicting
      malignancy was evaluated prospectively in 259 pathologically verified thyroid
      nodules. Sonographic and pathologic correlation of calcifications was performed
      on 69 of 99 surgically removed nodules. Pathologic studies revealed that
      hyperechoic areas with acoustic shadowing represented mostly amorphous dense
      calcifications and sometimes microcalcifications, but small particles without
      acoustic shadowing mainly reflected microcalcifications and sometimes large
      amount of fibrous bands and condensed colloids. Of the various sonographic signs,
      microcalcification showed the highest accuracy (76%), specificity (93%), and
      positive predictive value (70%) for malignancy as a single sonographic sign, but
      its sensitivity (36%) was poor. Although sonographic microcalcification showed
      relatively high specificity, the accuracy of this finding for malignancy was
      insufficient.

PMID- 7730465
TI  - Refractory hemolytic anemia secondary to perivalvular leak diagnosed by
      transesophageal echocardiography.
AB  - Transesophageal echocardiography (TEE) has become increasingly important in the
      assessment of mitral valve prosthetic dysfunction. We report on three patients
      who developed medically refractory hemolytic anemia after St. Jude mitral valve
      replacement secondary to perivalvular mitral prosthetic regurgitation. Two of the
      three cases had corrective surgical intervention that resolved the hemolytic
      process. Careful transesophageal echocardiographic evaluations of the
      perivalvular area proved diagnostic and resulted in appropriate management
      decisions.

PMID- 7730466
TI  - Color Doppler ultrasound and prenatal diagnosis of cleft palate.

PMID- 7730467
TI  - The use of color Doppler in the diagnosis of occult breast cancer.

PMID- 7730468
TI  - Transvaginal sonographic confirmation of a displaced intrauterine laminaria tent
      not seen on transabdominal examination.

PMID- 7730469
TI  - Synovial osteochondromatosis of the hip: role of sonography.

PMID- 7730470
TI  - Fetal splenic cyst: change in size and shape with advancing menstrual age.

PMID- 7730471
TI  - Sonographic appearance of an aberrant pancreas with unusual characteristics.

PMID- 7730472
TI  - Abdominoscrotal hydrocele: diagnosis by sonography.

PMID- 7730474
TI  - Contribution of immunophenotype in the diagnosis and classification of
      haemopoietic malignancies.

PMID- 7730473
TI  - The leukaemic phase of non-Hodgkin's lymphoma.

PMID- 7730475
TI  - Internal quality assurance in a clinical virology laboratory. II. Internal
      quality control.
AB  - AIMS: In April 1991 additional quality control procedures were introduced into
      the virology section of the Clinical Microbiology and Public Health Laboratory,
      Cambridge. Internal quality control (IQC) samples were gradually included in the
      serological assays performed in the laboratory and supplemented kit controls and
      standard sera. METHODS: From April 1991 to December 1993, 2421 IQC procedures
      were carried out with reference sera. RESULTS: The IQC samples were evaluated
      according to the Westgard rules. Violations were recorded in 60 of 1808 (3.3%)
      controls and were highest in the IQC samples of complement fixation tests (25/312
      (8%) of controls submitted for complement fixation tests). CONCLUSIONS: The
      inclusion of IQC samples in the serological assays performed in the laboratory
      has highlighted batch to batch variation in commercial assays. The setting of
      acceptable limits for the IQC samples has increased confidence in the validity of
      assay results.

PMID- 7730476
TI  - Multiplex PCR for identifying mycobacterial isolates.
AB  - AIMS: To develop a multiplex polymerase chain reaction (PCR) method to facilitate
      identification of mycobacterial isolates. METHODS: Type strains of 14 species of
      mycobacteria and 56 clinical isolates were lysed by boiling in TE Triton. The
      lysate (5 microliters) was used directly in a PCR reaction incorporating three
      pairs of PCR primers expected to amplify fragments from the genome of (a) all
      mycobacteria, (b) Mycobacterium tuberculosis complex only and (c) M avium only.
      PCR products were visualised by electrophoresis on agarose gels. RESULTS:
      Multiplex PCR applied to 14 type strains yielded patterns on electrophoresis
      which permitted identification of the mycobacterial isolates as M tuberculosis
      complex, M avium or as mycobacteria other than the former. The identification of
      56 clinical isolates by multiplex PCR was consistent with other methods and was
      accomplished in less than one working day. CONCLUSIONS: This method may
      facilitate rapid and convenient identification of most clinical isolates of
      mycobacteria by PCR and gel electrophoresis. Further evaluation is warranted.

PMID- 7730477
TI  - Avidity of specific IgG antibodies elicited by immunisation against Haemophilus
      influenzae type b.
AB  - AIM: To investigate the avidity of specific IgG polyribosyl ribitol phosphate
      (PRP) antibodies induced by three Haemophilus influenzae type b (Hib) conjugate
      vaccines: PRP-meningococcal outer membrane protein complex (PRP-OMP), PRP-non
      toxic mutant diphtheria toxin, CRM197 (HbOC) and PRP-tetanus toxoid (PRP-T).
      METHODS: One hundred and ten infants were immunised with one of the vaccines at
      two, three and four months of age. Blood samples were taken after each
      vaccination and serum stored at -20 degrees C. Serum samples collected after the
      third course (that is, at five months of age) were submitted to antibody avidity
      assessment, using a urea enzyme linked immunosorbent assay (ELISA). RESULTS: All
      three conjugate vaccines elicited IgG PRP antibodies of high median avidity. The
      resultant antibody populations were heterogeneous with regard to avidity, which
      in turn was independent of PRP antibody concentration. CONCLUSIONS: With the
      recent findings of a correlation between bactericidal killing and affinity, our
      data highlight the need for a protective level to be expressed qualitatively as
      well as quantitatively.

PMID- 7730478
TI  - Use of the Pastorex aspergillus antigen latex agglutination test for the
      diagnosis of invasive aspergillosis.
AB  - AIMS: To evaluate the Pastorex aspergillus antigen latex agglutination test for
      the diagnosis of invasive aspergillosis in patients undergoing liver or bone
      marrow transplantation. METHODS: Serum samples were taken at least twice weekly
      post-transplant and tested for Aspergillus antigen. Latex agglutination test
      results were compared with microbiological examination of respiratory, urine and
      bile specimens. Serum samples from liver transplant patients were also tested for
      antibodies to Aspergillus fumigatus by counter immunoelectrophoresis. RESULTS:
      Eight of the 91 patients studied developed invasive aspergillosis. Positive latex
      agglutination tests were obtained in eight of 187 (4.3%) serum samples from four
      of these eight patients. The other four patients with invasive aspergillosis gave
      consistently negative latex agglutination tests. A positive latex agglutination
      test was the first indication of invasive aspergillosis in two patients; these
      patients were already on amphotericin B. Positive latex agglutination tests were
      the only evidence of invasive aspergillosis in one patient who subsequently died
      of the infection. False positive latex agglutination tests were obtained in five
      of 83 (6%) patients with no evidence of invasive aspergillosis and misleading
      positive cultures seen in nine of 83 (10.8%). No antibodies were detected in
      three of four liver transplant patients with invasive aspergillosis. Conversely,
      antibodies were detected in 63 of 262 (24%) serum samples from 43 liver
      transplant patients with no evidence of invasive aspergillosis; one of these
      patients had an antibody titre of 1:2 on four separate occasions. CONCLUSIONS:
      The Pastorex aspergillus antigen latex agglutination test, when used alone, lacks
      sensitivity and specificity for the early diagnosis of invasive aspergillosis. A
      diagnosis was made in all patients with invasive aspergillosis when both culture
      and antigen tests were performed although using these criteria a false positive
      diagnosis would have been made in 13 of 83 (15.6%) patients. Microbiological and
      serial serological investigations for antigen should both be performed and the
      results considered in conjunction with radiological and clinical evidence.

PMID- 7730479
TI  - Detection of Chlamydia trachomatis antigen by enzyme immunoassay: importance of
      confirmatory testing.
AB  - AIM--To determine when a fluorescence assay for Chlamydia trachomatis elementary
      bodies in the specimen buffer is of most value as a verification test for genital
      specimens reactive on screening enzyme immunoassay (EIA). METHOD--Genital swabs
      from high and medium prevalence populations were tested using EIA. Samples with
      absorbance values greater than the positive threshold and those within the range
      of 30% below this value were verified by the MicroTrak direct fluorescence assay
      (DFA) test. Quotients derived from the threshold value and specimen absorbances
      were used to establish confidence limits for the EIA. RESULTS--Of 13,283 swabs
      tested, 474 from the high risk group and 236 from the medium risk group were
      reactive on EIA and confirmed by DFA. Thirty six (5.9%) patients with confirmed
      reactive samples would have been missed if the kit criteria alone were followed.
      When confidence limits were applied to the calculated quotients, only those
      samples with an EIA quotient of > or = 4.0 were universally confirmed by the DFA.
      CONCLUSION--A scheme of testing which uses the DFA to verify EIA reactive
      specimens over a specified range was found to improve the sensitivity and
      specificity of the EIA screening test.

PMID- 7730480
TI  - Molecular markers for diagnostic cytology of neoplasms in the head region of the
      pancreas: mutation of K-ras and overexpression of the p53 protein product.
AB  - AIMS: To determine the potential efficiency of molecular markers specific for
      neoplastic change--mutations of the K-ras oncogene and the p53 tumour suppressor
      gene--in diagnosing pancreatic carcinoma. METHODS: Archival cytology samples
      obtained from 17 patients with established pancreatic carcinoma were assayed for
      alterations in K-ras and p53. To detect changes in p53 expression,
      immunocytochemistry with polyclonal antibody CM1 was performed on the archival
      cytology slides after destaining. Mutations in K-ras codon 12 were then analysed
      on the scrapings of the same slides using mutant enriched polymerase chain
      reaction (PCR) amplification and restriction fragment length polymorphism
      analysis with allele specific oligonucleotide hybridisation for confirmation and
      characterisation. RESULTS: False negative results were recorded for five of the
      cytology slides when compared with p53 immunostaining of the surgical resection
      specimen. These five cases had been stained previously with Giemsa which
      interacts adversely with the immunostaining in contrast to the Papanicolaou
      procedure. The K-ras codon 12 mutations followed the well established
      distribution frequency and spectrum for pancreatic cancer and corresponded with
      the findings in the resection specimens in all cases. Two scrapings yielded
      insufficient DNA for PCR. Importantly, for two cases with an inconclusive
      cytology diagnosis on routine light microscopy, the diagnosis was confirmed by
      one of the molecular markers. The application of the molecular markers increased
      the diagnostic accuracy of cytology in this small study from 76 to 89%.
      CONCLUSIONS: The study indicates that assessment of alterations in the K-ras and
      p53 genes may be a valuable adjunct to diagnostic cytopathology of the head
      region of the pancreas, although there are some difficulties which will have to
      be overcome.

PMID- 7730481
TI  - Iron metabolism and fungal infections in patients with haematological
      malignancies.
AB  - AIM: To determine whether iron metabolism influences the incidence of systemic
      fungal infection in patients with haematological malignancies. METHODS: The study
      population comprised 74 patients who had undergone myeloablative chemotherapy.
      Systemic fungal infections were classified as confirmed (histological
      confirmation or characteristic septate hyphae) or possible (antibiotic resistant
      fever which resolved following administration of intravenous amphotericin B,
      together with either typical radiographic lesions or massive oropharyngeal
      candidiasis). Parameters of iron metabolism included serum iron concentrations,
      total iron binding capacity, serum transferrin, and ferritin concentrations and
      transferrin saturation values. RESULTS: Patients who developed a fungal infection
      had substantially increased transferrin saturation values and ferritin
      concentrations at diagnosis together with low serum transferrin and high serum
      iron concentrations. This profile was present in patients with a fungal infection
      regardless of the underlying haematological disorder. CONCLUSION: Increased
      transferrin saturation values and high ferritin concentrations may be additional
      risk factors for the development of systemic fungal infection in patients with
      haematological malignancies.

PMID- 7730482
TI  - Serosal reaction in chronic gastric ulcers: an immunohistochemical and
      ultrastructural study.
AB  - AIM: To study the serosal reaction in gastrectomy specimens with benign chronic
      peptic ulcers. METHODS: Gastrectomy specimens were fixed in neutral buffered
      formalin and paraffin wax, and examined using immunohistochemical and
      ultrastructural techniques. RESULTS: Nine of the 22 (41%) cases examined showed
      reactive hyperplasia of the serosal cells. The cells were predominantly spindle
      shaped and were positive on staining with Cam 5.2, AE1/3 and for vimentin. Eight
      of nine were also positive for smooth muscle actin and five for desmin.
      Ultrastructural analysis of these cells suggests that they may be myofibroblastic
      in nature. CONCLUSIONS: These results support the concept of "multipotential"
      subserosal cells which may differentiate into surface serosa or, in the reactive
      state, modulate the thin cytoskeletal filaments and become more myofibroblastic.
      Particular care should be taken not to confuse these reactive serosal cells with
      carcinoma or smooth muscle tumours in endoscopic biopsy specimens.

PMID- 7730483
TI  - Histomorphometric classification of postmenopausal osteoporosis: implications for
      the management of osteoporosis.
AB  - AIMS: To define and group static and dynamic iliac crest histomorphometric
      parameters in women with established osteoporosis. METHODS: Iliac crest biopsy
      specimens from 146 white women were sectioned undecalcified and examined using
      image analysis. RESULTS: Five distinct groups were defined on the basis of
      histomorphometric changes in cell function: group 1, decreased osteoblastic and
      osteoclastic activity; group 2, decreased osteoblastic and increased osteoclastic
      activity; group 3, increased osteoblastic and osteoclastic activity; group 4, no
      bone surface cell activity; and group 5, apparently normal osteoblastic and
      osteoclastic activity. CONCLUSIONS: Five distinct subgroups of patients with
      postmenopausal osteoporosis can be defined based on changes in bone cell
      function. Defining cellular dysfunction in this way may be important for
      tailoring treatment regimens to the needs of individual patients.

PMID- 7730484
TI  - p53 expression in hepatocellular carcinoma in a population in Singapore with
      endemic hepatitis B virus infection.
AB  - AIMS: To study the expression and clinical significance (if any) of p53 protein
      in hepatocellular carcinomas (HCC) arising in a population with endemic hepatitis
      B virus (HBV) infection. METHODS: Immunohistochemical staining was performed on
      formalin fixed, paraffin was embedded histological sections of 46 HCC cases using
      an antihuman p53 monoclonal antibody; serial sections were also stained for
      hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and alpha
      fetoprotein (AFP). Nuclear p53 staining was assessed according to intensity
      (absent, weak or strong) and extent (< 5%, 6-25%, 26-50%, and > 50%) of positive
      cells. Tissue HBsAg, HBcAg and AFP were recorded as absent or present. RESULTS:
      The p53 protein was expressed in 35% (16 of 46) of HCCs; the positive rate in
      grade III/IV tumours (13 of 31; 42%) was higher than in grade I/II tumours (three
      of 15; 20%) but this was not statistically significant. HBsAg positive tumours
      showed almost the same proportion of p53 staining (11 of 29; 38%) as HBsAg
      negative ones (five of 17; 29%). CONCLUSIONS: The p53 protein was expressed in
      35% of HCC cases. There was no statistically significant correlation between HBV
      infection and p53 protein expression. Similarly, there was no definite
      correlation between p53 positivity and tumour size, histological grade or
      vascular invasion.

PMID- 7730485
TI  - Immunohistochemical detection of p53 and Bcl-2 proteins in Hashimoto's
      thyroiditis and primary thyroid lymphomas.
AB  - AIMS: To investigate whether immunohistochemical staining using p53 and/or bcl-2
      distinguishes between florid Hashimoto's thyroiditis and low grade mucosa
      associated lymphoid tissue (MALT) lymphoma of the thyroid. METHODS: Ten cases of
      Hashimoto's thyroiditis and eight of primary thyroid lymphoma were stained with
      monoclonal antibodies directed against p53 and bcl-2. RESULTS: In Hashimoto's
      thyroiditis most small lymphoid cells in mantle zones, within the thyroid
      parenchyma and in lymphoepithelial lesions expressed bcl-2 protein. Very
      occasional centroblasts in reactive germinal centres were positive for p53, but
      all other lymphoid cells from cases of Hashimoto's disease were negative for p53.
      In diffuse, low grade lymphomas bcl-2 protein was uniformly expressed by most
      tumour cells. However, low grade lymphomas with a follicular pattern did not
      express bcl-2. The diffuse, low grade lymphomas were negative for p53, while
      occasional larger cells in the follicular subtype were positive. Both high grade
      lymphomas were bcl-2 negative but strongly p53 positive. CONCLUSIONS: This study
      indicates that there is an inverse correlation between p53 and bcl-2
      immunostaining in thyroid lymphomas (low grade lymphomas: bcl-2 positive, p53
      negative; high grade lymphomas: bcl-2 negative, p53 positive). Furthermore,
      immunohistochemical staining for bcl-2 and p53 proteins does not distinguish
      florid Hashimoto's thyroiditis from diffuse, low grade thyroid lymphoma.

PMID- 7730486
TI  - Apoptotic and mitotic indices in malignant melanoma and basal cell carcinoma.
AB  - AIMS: To assess the relative frequency of mitotic and apoptotic cells in
      malignant melanoma and basal cell carcinoma. METHODS: Retrospective evaluation of
      haematoxylin and eosin stained slides from 10 basal cell carcinomas, 10 nodular
      melanomas, and 10 superficial spreading melanomas, with counting of apoptotic and
      mitotic cells per 1000 cells. Selected cases were studied with in situ end
      labelling. RESULTS: The ratio of apoptotic to mitotic cells was higher in basal
      cell carcinoma than in either form of melanoma because of the presence of a
      greater number of apoptotic cells in basal cell carcinoma. CONCLUSION: The
      differing growth rates and biological behaviour of these two tumours is reflected
      in the apoptotic:mitotic ratio. Further assessment of this ratio is warranted,
      both between tumour types and between individual tumours of one type, to
      determine its value as an indicator of biological potential.

PMID- 7730487
TI  - Audit of tumour histopathology reviewed by a regional oncology centre.
AB  - AIMS: To analyse the diagnostic differences in reporting tumour histopathology
      between a district general hospital and a regional oncology centre. METHODS:
      Tumour histopathology reports (n = 227) extracted from Bolton General Hospital
      files between 1988 and 1992 were compared with the corresponding Christie
      Hospital (oncology centre) reports, the same material having been seen at both
      hospitals. RESULTS: Diagnostic agreement existed in 77% of all cases. The
      incidence of major discrepancies was 8.37%. Of the diagnoses, 19 (36%) cases
      involved major discrepancies and 34 (64%) cases minor discrepancies. Most
      discrepancies occurred in the lymphoma group and involved subclassification of
      Hodgkin's and non-Hodgkin's lymphoma. Ki1 anaplastic large cell lymphoma and T
      cell rich B cell lymphoma were problematic diagnoses. The correct grading of
      follicle centre cell lymphomas using the Kiel classification was another problem
      area. In 19 cases certain aspects of immunohistochemistry produced discrepancies.
      In one case an incorrect diagnosis was made at the oncology centre and in another
      both centres gave an incorrect diagnosis. CONCLUSIONS: Areas of diagnostic
      difficulty mainly involve the subclassification of lymphomas. Review of tumour
      pathology by experts is recommended, at least in certain categories, to ensure
      correct diagnosis and uniformity in subclassification of tumours.

PMID- 7730488
TI  - Improvement of gastric inflammation and resolution of epithelial damage one year
      after eradication of Helicobacter pylori.
AB  - AIMS: To investigate the effect of eradication of Helicobacter pylori infection
      on gastric epithelial damage and gastritis, scored according to the Sydney
      system. METHODS: Gastritis scores and epithelial damage were assessed in gastric
      biopsy specimens before, and five weeks and one year after anti-H pylori therapy
      in 66 patients with H pylori related gastritis. RESULTS: The mean initial levels
      of activity, inflammation, atrophy, intestinal metaplasia, and H pylori scores
      were higher in the antrum than in the corpus or fundus. Eradication of H pylori
      resulted in an improvement in the mean inflammatory score in antral biopsy
      specimens from 2.23 before treatment to 1.32 and 1.06, respectively, five weeks
      and one year after treatment. Corresponding values for fundic biopsy specimens
      were 1.30, 0.36 and 0.35. Activity scores improved from 1.41 before treatment to
      0.13 and zero, respectively, five weeks and one year after treatment in antral
      biopsy specimens and from 0.60 before treatment to zero in fundic biopsy
      specimens. Before treatment, epithelial damage was present in 51% of biopsy
      specimens taken from the antrum and 23% of those from the corpus. Five weeks
      after eradication of H pylori none of the biopsy specimens revealed evidence of
      epithelial damage. CONCLUSION: Eradication of H pylori is followed by a rapid,
      significant improvement in the gastritis score and resolution of epithelial
      damage in antral and fundic mucosa.

PMID- 7730489
TI  - Functional hyposplenism following allogeneic bone marrow transplantation.
AB  - AIMS: To investigate the incidence of functional hyposplenism in a group of
      patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS:
      Splenic function was assessed by counting the number of gluteraldehyde fixed red
      blood cells containing pits or indentations as examined by interference phase
      microscopy. Normal values are < 2% whereas splenectomy patients have values of 25
      to 40%. RESULTS: Twenty eight BMT recipients (17 men, 11 women) were studied at
      varying periods post-transplant and the results compared with 20 healthy
      volunteers and 10 patients who had undergone splenectomy or had splenic atrophy
      because of haematological conditions. Of the 28 BMT recipients, one had undergone
      a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of
      functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four
      patients, one had active extensive chronic graft versus host disease (GvHD) which
      has been previously reported to be associated with functional hyposplenism
      following transplantation. Only one of the four patients had peripheral blood red
      cell changes typical of hyposplenism. CONCLUSION: These results confirm that
      extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of
      functional hyposplenism may also occur following BMT in the absence of chronic
      GvHD and in the absence of haematological features of hyposplenism on routine
      blood films. This may be of significance in mediating the susceptibility to
      infection with encapsulating bacteria seen following allogeneic BMT.

PMID- 7730490
TI  - Immunological factors and risk of infection in plateau phase myeloma.
AB  - AIMS: A series of patients with myeloma were investigated to assess whether
      immunological risk factors predisposing to serious infection could be identified.
      METHODS: Patients (n = 102) with predominantly plateau phase myeloma were
      monitored prospectively for infections. Immunological parameters including total
      non-paraprotein immunoglobulins and specific antibody titres were measured in all
      patients and compared with a control population of healthy individuals of a
      similar age; response to immunisation with Pneumovax II, tetanus and diphtheria
      toxoids and IgG subclasses were measured in a subgroup of 41 patients. Other
      characteristics investigated for any association with infection included age,
      sex, paraprotein type, disease stage, and chemotherapy. RESULTS: Specific
      antibody titres to pneumococcal capsular polysaccharides and tetanus and
      diphtheria toxoids were significantly reduced compared with the control
      population. Low antipneumococcal and anti Escherichia coli titres correlated with
      risk of serious infection and low anti-pneumococcal titres with severity of non
      paraprotein immunosuppression. In 41 immunised patients responses to Pneumovax
      II, tetanus and diphtheria toxoids were poor; IgG subclass levels were
      significantly reduced and a poor IgG response to Pneumovax II immunisation was
      associated with an increased risk of septicaemia and low IgG2 levels. The overall
      serious infection rate was 0.92 infections per patient year and was four times
      higher during periods of active disease (1.90) compared with plateau phase
      myeloma (0.49). The predominant site of infection was the respiratory tract.
      Clinical and laboratory parameters showed only male sex and reduced non
      paraprotein IgG and IgA levels to be significantly associated with at least one
      serious infection. CONCLUSIONS: A subgroup of patients with myeloma with poor IgG
      responses to exogenous antigens, who are at increased risk of serious infection,
      can be identified and may benefit from replacement immunoglobulin therapy to
      reduce the risk of infection.

PMID- 7730491
TI  - Dieulafoy's disease associated with early gastric cancer.
AB  - In the past different terms have been used to define the vascular malformations
      of Dieulafoy's disease--for example, calibre persistent artery of the stomach,
      cirsoid aneurysm and gastric atherosclerosis. A case of Dieulafoy's disease is
      described in a 41 year old man, who presented with symptoms of anaemia and
      melaena, with particular attention paid to the morphological characterisation of
      the vascular histological lesions. Intimal hyperplasia with a non-concentric
      proliferation of myointimal cells, areas of muscular degeneration, aspects of
      vascular neoformation of the arterial wall, and other findings are reported. An
      association between an early diffuse adenocarcinoma and parietal anomalies of
      Dieulafoy's disease is illustrated.

PMID- 7730492
TI  - Importance of hepatic artery node involvement in patients with colorectal liver
      metastases.
AB  - Hepatic artery lymph node (HALN) involvement is an adverse prognostic factor in
      patients treated for colorectal liver metastases. The prevalence of HALN
      positivity for mid-gut and hind-gut derived colonic tumours, for differing
      amounts of liver involvement, and for Dukes' A and B versus Dukes' C primary
      tumours was compared in 75 patients with colorectal liver metastases. All
      patients whose primary tumours did not invade lymph nodes (Dukes' A or B) had
      liver metastases that did not involve local hepatic nodes, regardless of the
      extent of the disease within the liver. This suggests that factors controlling
      metastasis are not identical with those which control lymphatic invasion in
      colorectal cancer. HALN positive patients may benefit less from treatment because
      they are significantly more likely to have both a greater burden of disease
      within the liver and a tumour with greater lymph invasive potential than patients
      with HALN negative liver metastases.

PMID- 7730493
TI  - An unusual case of colonic angiodysplasia.
AB  - An unusual case of a colonic vascular anomaly resembling angiodysplasia
      associated with right sided diverticular disease is presented. The patient, a 74
      year old man, presented with a four day history of rectal bleeding and
      subsequently underwent hemicolectomy. The resected specimen was flushed out with
      heparin-saline solution and injected with a barium-gelatine mixture. Preoperative
      barium enema revealed right sided diverticula, whereas post-resection
      angioradiography revealed the "coral reef" vascular anomaly consistent with
      angiodysplasia. Histology confirmed the presence of both diverticular disease and
      angiodysplasia. This case report highlights the importance of considering a
      vascular anomaly in patients presenting with rectal bleeding despite the presence
      of another radiologically demonstrable anatomical lesion.

PMID- 7730494
TI  - B cell signet-ring cell lymphoma of bone marrow.
AB  - A case of signet-ring cell lymphoma affecting the bone marrow and diagnosed by
      bone marrow trephine biopsy is reported. Normal marrow was replaced totally by
      cells with large central vacuoles, many of which displaced the nucleus to the
      periphery of the cell, imparting a signet-ring appearance. Initially, the
      favoured morphological diagnosis was metastatic signet-ring adenocarcinoma, but
      on immunocytochemistry the tumour cells were strongly positive for CD45
      (leucocyte common antigen) and the B cell marker CD20 (L26). Electron microscopy
      revealed electron-lucent vacuoles with no discernable internal structure. The
      tumour was classified as a high grade centroblastic lymphoma using the upgraded
      Kiel classification. Despite chemotherapeutic treatment, the patient died during
      an episode of septicaemic shock within two months of presentation.

PMID- 7730495
TI  - Degenerative changes in myometrium simulating diffuse leiomyomatosis after
      treatment with gonadotrophin releasing hormone analogue.
AB  - Degenerative changes are encountered relatively frequently in uterine leiomyomas.
      Morphologic changes within leiomyomas, particularly necrosis and alterations in
      cellularity, have been described following treatment with gonadotrophin releasing
      hormone analogue, but the effects of this form of treatment on the morphology of
      the normal myometrium are less well documented. A case is reported of a 42 year
      old woman with a history of menorrhagia in whom a combination of degenerative and
      iatrogenic changes resulted in a histological appearance resembling diffuse
      leiomyomatosis.

PMID- 7730496
TI  - Mode of action of atypical neuroleptics in relation to the phencyclidine model of
      schizophrenia: role of 5-HT2 receptor and alpha 1-adrenoceptor antagonism
      [corrected].
AB  - In experiments in rats, by the use of single-cell recordings from midbrain
      dopamine (DA) neurons of the ventral tegmental area (VTA), the systemic
      administration of the schizophrenomimetic N-methyl-D-aspartate receptor
      antagonists phencyclidine (PCP) or dizocilpine (MK-801) caused an increased
      firing rate but reduced the variability of firing in VTA DA neurons. Burst firing
      was increased in cells predominantly located in the paranigral nucleus, a
      subdivision of the VTA largely projecting to the nucleus accumbens and other
      limbic regions, but reduced in DA cells predominantly located in the parabrachial
      pigmented nucleus, another subdivision of the VTA that projects largely to the
      prefrontal cortex (PFC). Thus, a severely impaired signal-to-noise ratio within
      the PFC DA projection was obtained, concomitant with an overactive mesolimbic DA
      system. The administration of high doses of ritanserin or atypical neuroleptics
      with prominent serotonin (5-hydroxytrypyamine) 5-HT2 receptor antagonist action,
      such as clozapine or amperozide, produced preferential activation of the PFC DA
      projection. In contrast, the selective D2 receptor antagonist raclopride caused a
      greater activation of the subcortical than cortical DA projections, as assessed
      by microdialysis experiments in vivo from our laboratory. Adding ritanserin
      treatment to raclopride markedly enhanced the raclopride-induced increase in DA
      levels in the medial PFC, an effect probably mediated by augmentation of the
      raclopride-induced increase in the burst firing of meso-cortical DA neurons, but
      failed to affect the action of raclopride on striatal DA levels.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7730497
TI  - The role of serotonin in schizophrenia and the place of serotonin-dopamine
      antagonist antipsychotics.
AB  - After four decades of the use of antipsychotic drugs that target the dopamine D2
      receptor as the initial site of action, a new strategy for antipsychotic therapy
      has emerged and, with it, new hope for greater efficacy and fewer side effects.
      This new strategy involves identifying drugs with strong serotonin (5
      hydroxytryptamine) 5-HT2A receptor relative to dopamine D2 receptor blocking
      properties. Clozapine is now known to have these properties, but risperidone is
      the first drug to be designed intentionally to have these properties. Others are
      being developed. These drugs, the serotonin-dopamine antagonists (SDAs), may
      prove to have many other uses in psychiatry beyond schizophrenia because of their
      low propensity to cause extrapyramidal symptoms. Their pharmacologic mechanism of
      action may be more complex than only strong 5-HT2A and weak D2 block, e.g., 5
      HT2C and D4 receptor blockade. Nevertheless, the SDAs are proving to be valuable
      tools in the analysis of both normal brain function and the etiology of
      schizophrenia.

PMID- 7730498
TI  - Serotonin-dopamine antagonists and treatment of negative symptoms.
AB  - This review aims to examine the basis of the hypothesis that simultaneously
      modifying serotonergic and dopaminergic neurotransmission is effective in
      schizophrenia and to assess critically clinical efficacy data with respect to
      negative symptoms. A variety of serotonin and dopamine agonists can induce
      psychosis, so it is to be expected that certain serotonin and dopamine
      antagonists could have antipsychotic effects. It is known that serotonergic
      afferent neurons synapsing with dopaminergic neurons exert an inhibitory effect.
      Because hypodopaminergic pathophysiology has been postulated as being responsible
      for negative symptoms, serotonin antagonists may be therapeutic. A number of
      clinical trials provide data on the effect of adding serotonergic drugs to
      conventional neuroleptics in the treatment of schizophrenia, and there are now
      studies with drugs that combine serotonin and dopamine antagonism in the same
      molecule. There may be a modest enhancement of the antipsychotic effect of
      antagonism at postsynaptic dopamine D2 receptors. The effects of serotonin
      antagonism on negative symptoms are, however, more encouraging, although the
      issue is complicated because methodologic difficulties confound the
      interpretation of the results of these studies. The weight of the evidence
      suggests that negative symptoms improve when the treatment of schizophrenia
      includes drugs that diminish serotonergic activity. However, this may be because
      of indirect effects, such as an enhanced antipsychotic action, diminished
      extrapyramidal side effects, increased activation, or decreased depression--all
      features associated with secondary negative symptoms. The challenge is to address
      primary negative symptoms, and this has been attempted in a small number of
      patients; the results are not very encouraging.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730499
TI  - The evolution of the serotonin-dopamine antagonist concept.
AB  - Before the dopamine hypothesis of schizophrenia became established, a serotonin
      (5-hydroxy-tryptamine) 5-HT hypothesis was popular. This was based on the
      hallucinogenic properties of lysergic acid diethlyamide and abnormal serotonin
      levels in schizophrenics. Suggestions that serotonin might be involved in the
      cause of schizophrenia or could be a target for antipsychotic drug action began
      with the discovery that the antipsychotic agent clozapine is a potent serotonin 5
      HT2A antagonist, as well as being a dopamine D2 antagonist. This led to the
      formulation of the serotonin-dopamine antagonist (SDA) concept for
      antipsychotics, with wider spectrums of activity and lower extrapyramidal side
      effects (EPS) liability. The principle of the SDAs is that the drug should be a
      potent serotonin 5-HT2A antagonist, with slightly less potent dopamine D2
      receptor-blocking properties. The clinical experience with risperidone, the first
      member of the new class of antipsychotics, seems to offer the promise that the
      SDAs have significant advantages over both the conventional dopamine-blocking
      neuroleptics and the atypical antipsychotic clozapine. Risperidone has efficacy
      against both the positive and negative symptoms of schizophrenia and has a low
      tendency to produce EPS. Only time will tell whether other SDAs will have the
      same advantages.

PMID- 7730500
TI  - Role perceptions of freshman and senior nursing and medical students and
      attitudes toward collaborative decision making.
AB  - David Kolb's (1981) experiential learning theory was used to examine differences
      between first- and fourth-year nursing and medical students' perceptions of
      competencies important for nursing and medicine. A convenience sample of nursing
      (n = 109) and medical (n = 108) students from a large Canadian research
      university was surveyed. Respondents completed the Environmental Press
      Questionnaire, the Adaptive Competency Scale, and a 6-item measure of attitudes
      toward collaborative nurse-physician patient care decision making. Nursing
      students' perceptions of competencies important for medicine were found to be
      more congruent with medical students' perceptions of these competencies than were
      medical students' perceptions of competencies important for nursing as seen by
      nursing students. Gaps in perceptions of each others' roles were significantly
      negatively related to attitudes toward collaborative patient care decision
      making.

PMID- 7730501
TI  - Respecting the nontraditional student.

PMID- 7730502
TI  - The nurse executive. Breaking the cycle.

PMID- 7730503
TI  - Professional practice. Transgressor or revolutionary?

PMID- 7730504
TI  - Public policy. Continuing to beat the prevention drum.

PMID- 7730505
TI  - A statewide model for promoting research.

PMID- 7730506
TI  - Nurse-managed clinics: a blueprint for success using the Covey framework.
AB  - This article describes the process from inception to successful operation of a
      university-based nurse managed clinic. The article includes information regarding
      the planning process, method of financing, political strategies for gaining
      approval, and on-going development of services. Covey's seven habits of highly
      effective people are used as a framework on which the development and evolution
      of the clinic are based. The habits are illustrated by relating how
      services/operation were enhanced and barriers and obstacles were overcome.

PMID- 7730507
TI  - Faculty practice: creating a new culture.
AB  - This article provides specifics on the development of a clinical track for
      faculty appointments at the University of Pittsburgh. The criteria to be used for
      appointment and promotion on the clinical track are discussed along with the
      practice requirements of 60 hours per term of participation in and responsibility
      for direct care of patients. The purposes of faculty practice are set forth along
      with the formation and functioning of a Faculty Practice Council which handles
      decisions related to faculty practice. Results of the first year after
      implementation of a clinical track showed that 64 per cent (18) of the faculty
      had met all of their faculty practice obligations; of the remaining 36 percent
      (10) who had not, a variety of circumstances were cited. The Income to the School
      of Nursing for faculty practice, although modest, has helped to highlight that
      practice is valued and an integral part of the faculty role.

PMID- 7730508
TI  - Nursing faculty--an endangered species?
AB  - A present faculty shortage has been documented, and the potential for an even
      worse shortage in the future is very real. Implications of a continued shortage
      for both nursing education and practice are serious. They include limitations on
      enrollments leading to future nursing shortages, burnout of present faculty, or
      possible decline in the quality of programs. Contributing factors such as aging
      of educators, fewer graduate students going into teaching, non-competitive
      salaries, and increased job opportunities for nurses with graduate degrees are
      explored. Possible solutions include adding more education courses or tracks in
      graduate programs, obtaining increased federal funds for graduate education,
      emphasizing the many rewards and benefits of the faculty role, recruiting faculty
      from new areas, mentoring people into teaching, giving flexible teaching
      assignments to older faculty members, and making changes in the ways that
      clinical instruction is performed.

PMID- 7730509
TI  - Mentoring in the career development of hospital staff nurses: models and
      strategies.
AB  - Mentoring in the career development of hospital staff nurses was explored using a
      qualitative, grounded-theory method in a descriptive study design. Verbatim
      audiotaped interviews of hospital staff nurses and their nurse managers from four
      hospitals in the northeast were used. Document analysis of key hospital and
      nursing organizational policy statements was included. Two models were identified
      from the study regarding the mentoring of hospital staff nurses, ie, a structural
      and a process model. Within the structural model, mentoring influentials were
      noted to be people, events, and environments. Peers and nurse managers proved to
      be the primary people influential in providing key mentoring strategies. Within
      the process model, four phases were identified leading to three separate career
      development outcomes toward which hospital staff nurses strive: the development
      of career-building relationships, facilitation of career transition points, and
      positive interaction within the organizational climate.

PMID- 7730510
TI  - Nurses' judgment as they care for persons who exhibit impaired judgment: a
      phenomenological study.
AB  - The purpose of this phenomenological study was to discover the process by which
      psychiatric nurses make judgments as they care for persons who exhibit impaired
      judgment. Data were collected from six experienced psychiatric nurses in a
      private room and were audiotaped. These data were analyzed using Spiegelberg's
      (1976) phenomenological method. The data yielded an overarching theme: all the
      nurses presented judgment as a personal responsibility. Within this overarching
      theme, were four major themes: (1) closeness to the clinical data; (2) critical
      reflection; (3) respect for one's knowledge and ignorance; and (4) existential
      nature of judgment. Categories within theme (1) closeness to the clinical data
      were nurse as knower and focus on the patient; within theme (2), critical
      reflection were experience and understanding; within theme (3), respect for one's
      knowledge and ignorance were self-consciousness and expectation of self; and
      within theme (4), existential nature of judgment were alone facing the unknown
      and "Eureka! I've got it!" Essentially, judgment occurred privately within the
      mind of the nurse, making it both the creation and responsibility of the nurse.
      For these nurses judgment was the pivotal event in nursing inquiry beginning in
      the desire to know, proceeding through understanding and presentation of a
      nursing problem and then determining the question, "What is it?" in a "Eureka!"
      moment. With this experience of "I've got it!" the nurse crossed from the unknown
      to the known. Judgment which began in the desire to know began again with a new
      question.

PMID- 7730511
TI  - Commentary on the IOM report. Oral health objectives.

PMID- 7730512
TI  - Commentary on the IOM report. The mission of education.

PMID- 7730513
TI  - Commentary on the IOM report. The mission of research.

PMID- 7730514
TI  - Commentary on the IOM report. Patient care.

PMID- 7730515
TI  - Commentary on the IOM report. Dental schools and the university.

PMID- 7730516
TI  - Commentary on the IOM report. Accreditation and licensure.

PMID- 7730517
TI  - Commentary on the IOM report. Work force issues.

PMID- 7730518
TI  - The National Academy of Sciences/Institute of Medicine.

PMID- 7730519
TI  - Master planner: William J. Gies and dentistry's 20th century coming of age.

PMID- 7730520
TI  - The case of the unsound business decision.

PMID- 7730521
TI  - The earning potential of professionals.

PMID- 7730522
TI  - Profiles in professionalism: 1994 ACD awardees. William John Gies Award.

PMID- 7730523
TI  - The future of dental education: a report from the Institute of Medicine.

PMID- 7730524
TI  - IOM Report. Dental education at the crossroads. Summary of recommendations.
      United States National Academy of Sciences. Institute of Medicine.

PMID- 7730525
TI  - Effect of sustained resistance training on basal metabolic rate in older women.
AB  - OBJECTIVE: To determine if basal metabolic rate (BMR) could be elevated in older
      women undertaking a program of progressive resistance exercise of up to 52-weeks
      duration. DESIGN: Randomized controlled trial with subjects assigned to either a
      control (CO), high-intensity (HI), or low-intensity (LO) training group for 15
      weeks. BMR, body composition, energy intake and expenditure, and muscle strength
      were assessed at baseline and after 15 weeks. Subjects were encouraged to
      continue in their assigned exercise group for an additional 37 weeks, after which
      time they were reevaluated. SETTING: An exercise facility at a medical center.
      SUBJECTS: Thirty-six community-dwelling healthy women aged 65 to 79 years.
      INTERVENTION: Exercise groups performed three sets of 10 exercises, 3 days/week,
      at either 80% of one-repetition maximum (1-RM) for seven repetitions (HI) or 40%
      of 1-RM for 14 repetitions (LO). MEASURES: BMR by indirect calorimetry, body
      composition by dual energy X-ray absorptiometry, energy intake and expenditure
      from 4-day dietary and activity records, and dynamic muscle strength by 1-RM.
      RESULTS: Muscle strength increased, on average (+/- SEM), by 40 +/- 6% and 36 +/-
      7% in the HI and LO groups after 15 weeks, respectively, compared with 4 +/- 1%
      in the nonexercising subjects (P = .0001). Fat mass decreased after 15 weeks in
      LO exercisers by 1.0 kg (P < .05), whereas there was a trend for fat-free mass
      (FFM) to increase in the HI group by 0.7 kg (P = .08). No change occurred in any
      group for BMR. From weeks 15 to 52, muscle strength increased a further 9 +/- 2%
      and 11 +/- 2% in HI and LO groups, respectively, compared with 3 +/- 1% in
      nonexercisers (P < .005). There was no change in BMR or any body composition
      parameter during this time period. CONCLUSIONS: Neither training program
      significantly altered BMR and both produced only minimal changes in body
      composition. However, both the HI and LO exercise regimens resulted in similar
      and substantial gains in upper and lower body muscle strength that persisted over
      the course of the year. This suggests that either exercise regimen may prove an
      effective strategy for preventing frailty and maintaining functional independence
      in older adults.

PMID- 7730526
TI  - Assessing diagnostic approaches to depression in medically ill older adults: how
      reliably can mental health professionals make judgments about the cause of
      symptoms?
AB  - OBJECTIVE: To evaluate the reliability of the DSM-IV approach and five other
      schemes for counting symptoms toward the diagnosis of depression in hospitalized
      medically ill older patients and to examine whether mental health professionals
      can reliably make judgments about the etiology (medical or psychological) of
      depressive symptoms. METHOD: A sample of 38 patients aged 60 years or older
      admitted to the general medicine, cardiology, or neurology services at Duke
      University Medical Center were evaluated for depression using a structured
      psychiatric interview and the Hamilton Depression Scale. Interrater reliability
      for the diagnostic schemes, for unstructured clinical diagnoses, and for
      determinations of the causes of individual depressive symptoms was assessed by
      three pairs of mental health professionals. RESULTS: Agreement between raters for
      structured diagnoses was high regardless of diagnostic strategy, with the DSM-IV
      approach being only slightly less reliable than the strict inclusive approach
      (Kappa 0.88 vs Kappa 1.0, respectively). For all diagnostic approaches, there was
      perfect agreement between raters for eight cases of major depression. Agreement
      for unstructured clinical diagnoses of depression (K = 0.50) was much lower than
      for the structured diagnoses. Agreement between raters on the etiology of
      individual depression criterion symptoms assessed by structured interview was
      greater than 80% for 14 of 19 symptoms. Correlation between raters' depression
      severity ratings on the Hamilton Scale using the DSM-IV etiologic approach was
      equivalent to that using the strict inclusive approach (0.98 vs 0.95,
      respectively). CONCLUSIONS: Mental health professionals can be trained to make
      judgments reliably about the cause (medical or psychological) of symptoms in
      hospitalized older medical patients. The "strict inclusive" and other diagnostic
      schemes for counting symptoms toward the diagnosis of depression have only
      marginal, if any, benefit compared with the current DSM-IV approach.

PMID- 7730527
TI  - Foot pain and disability in older persons: an epidemiologic survey.
AB  - OBJECTIVE: To investigate the prevalence of foot pain in older people and its
      association with pathological conditions of the feet and with disability in basic
      and instrumental activities of daily living. DESIGN: Cross-sectional survey of a
      community-dwelling older population. PARTICIPANTS: A total of 459 subjects, 73%
      of the population aged 65 years and older living in Dicomano, Florence, Italy.
      MEASUREMENTS: A standardized medical examination was performed by a geriatrician
      to collect information on the presence of pain, specific problems of the feet,
      gait, and several indicators of physical health status. Disability in basic and
      instrumental activities of daily living was evaluated by self-report. RESULTS:
      The prevalence of foot pain was very high, especially in subjects affected by
      calluses or corns, hallux deformities, hammer toes, pes planus, and edema and
      among those who complained of difficulty in looking after the basic needs of the
      feet. Patients with foot pain needed a greater number of steps and longer time to
      walk the same distance. Foot pain was associated with a higher prevalence of
      disability in instrumental activities of daily living, particularly those related
      to standing and ambulation capacities, but it was not related to higher
      prevalence of disability in basic activities of daily living. CONCLUSIONS: Foot
      pain is associated with specific conditions of the feet and disability in
      instrumental activities of daily living. Adequate assessment and treatment of
      foot problems may prevent foot pain and potentially reduce risk of disability.
      This hypothesis needs to be tested in longitudinal studies and specific
      intervention trials.

PMID- 7730528
TI  - Social and leisure activities and risk of dementia: a prospective longitudinal
      study.
AB  - OBJECTIVE: To study the relationship between social and leisure activities and
      risk of subsequent dementia in older community residents. SETTING: A cohort study
      of people aged 65 and older were followed-up 1 and 3 years after a baseline
      screening (the Paquid study). PARTICIPANTS: 2040 older subjects living at home in
      Gironde (France) were randomly selected and followed for at least 3 years. DATA
      COLLECTION: Information about social and leisure activities was collected during
      the baseline screening with an interview by a psychologist. Incident cases of
      dementia were detected during the first and third year follow-up screenings
      according to the DSM-III-R criteria. MAIN RESULTS: All but one of the social and
      leisure activities noted were significantly associated with a lower risk of
      dementia. Only golden club participation was not significantly associated with
      this risk. After adjustment for age and cognitive performance measured by the
      Mini-Mental State Exam, visual memory test, and verbal fluency test, only
      traveling (Relative risk (RR) = .48,95% Confidence Interval (95% CI) = .24-.94),
      odd jobs or knitting (RR = .46,95% CI = .26-.85), and gardening (RR = .53, 95% CI
      = .28-.99) remained significant. CONCLUSIONS: Regular participation in social or
      leisure activities such as traveling, odd jobs, knitting, or gardening were
      associated with a lower risk of subsequent dementia.

PMID- 7730529
TI  - Serum anticholinergic activity in hospitalized older persons with delirium: a
      preliminary study.
AB  - OBJECTIVE: To evaluate the relationship between total serum anticholinergic
      activity (SAA) and the presence or absence of delirium in older hospitalized
      persons on general medical wards. DESIGN: Case-control study and within-subjects
      repeated-measures in recovered delirious patients. SETTING: Minneapolis Veterans
      Affairs Medical Center medical wards. PARTICIPANTS: Eleven male delirious
      patients (DSM-III-R criteria) aged 60 or older and 11 comparably aged male
      nondelirious controls. MEASUREMENTS: Radioreceptor bioassay of total SAA using
      tritiated quinuclidinyl benzilate (QNB) binding to muscarinic receptors. Results
      are expressed in terms of atropine equivalents (nM). MAIN RESULTS: Mean SAA was
      significantly elevated in the delirious group (mean +/- SD = 6.05 +/- 2.97 nM
      atropine equivalents) compared with the controls (3.38 +/- 2.49; t(20) = 2.28, P
      < .05). At study entry, mean SAA was significantly higher in delirious subjects
      whose symptoms eventually resolved completely (mean +/- SD = 7.77 +/- 2.37)
      compared with subjects whose delirious symptoms persisted (3.99 +/- 2.30; t(9) =
      2.68, P < .05). All six patients in whom delirium resolved completely had a
      decrease in serum anticholinergic activity when measured during delirium (7.77 +/
      2.37) and after symptom resolution (3.92 +/- 2.61; t(5) = 3.29, P < .05).
      CONCLUSIONS: Our findings suggest that serum anticholinergic activity may play a
      role in delirium in medical inpatients. The relationships between SAA and
      delirium in medical patients and between total SAA and medication use warrant
      further study.

PMID- 7730530
TI  - Cost of pressure ulcer prevention in long-term care.
AB  - OBJECTIVE: To describe the total cost of pressure ulcer prevention, component
      costs of each intervention, and the relationship of costs to subjects' risk
      level. DESIGN: 3-month cohort trial. SETTING: A 600-bed, state-supported, long
      term care facility. PATIENTS: A total of 539 war veterans, 83% of whom were male;
      mean age was 73 years. MAIN OUTCOME MEASURES: Cost to facility for using each of
      four preventive interventions: turning, pressure-reducing mattresses, chair
      cushions, miscellaneous preventive devices. RESULTS: Sixty-eight percent of
      subjects received a preventive intervention. Total 3-month facility cost of
      prevention was $132,114, and 97% of the cost was consumed by 30% of the subjects.
      Turning was the most expensive component, accounting for $99,567. The daily cost
      of turning for subjects who received it was $8.83 +/- 1.66. Cost increased with
      subject risk level. Low cost devices were instituted for lower risk subjects,
      whereas high cost interventions (turning) were reserved for the highest risk
      subjects. CONCLUSIONS: This long-term care facility expended substantial
      resources on prevention, and most resources (97%) were expended on less than half
      (30%) of subjects. Turning was, by far, the most expensive intervention, and the
      nursing staff reserved it for highest risk subjects. Strategies that substitute
      moderately priced mattresses for frequent turning may decrease the cost of
      prevention, as long as mattress cost is less than the daily turning costs it
      replaces. Future research to define the optimum combinations of preventive
      interventions for patients of various risk levels is needed.

PMID- 7730531
TI  - Functional and mobility impairments associated with Paget's disease of bone.
AB  - OBJECTIVE: To determine if patients with Paget's disease of bone involving the
      tibia, femur, and/or acetabular portion of the ilium had more impairments in
      function and mobility than age- and sex-matched control subjects. PATIENTS AND
      METHODS: A case control study with Paget's disease patients selected from a
      center for bone disease at a tertiary medical center; control subjects were
      volunteers from the Duke University Aging Center subject registry. Demographic
      characteristics, physical examination and serum alkaline phosphatase levels were
      obtained. Radiographs of the pelvis and lower extremities were evaluated by a
      radiologist. All participants completed a Functional Status Questionnaire (FSQ).
      Mobility measures included mobility skills protocol, 10-foot walk time, 360
      degree turn left (number of steps), and 6-minute walk distance. RESULTS: The 12
      Paget's disease patients were no different in age (70.7 +/- 6.2 years) than the
      12 control subjects (69.5 +/- 6.2 years). Serum alkaline phosphatase levels were
      elevated in Paget's patients (539 +/- 530 IU/L), and normal in control subjects
      (85 +/- 17 IU/L). In addition to Paget's disease, radiographs showed joint space
      loss in joints proximate to the diseased bone. On the FSQ scales Paget's disease
      patients had significantly lower scores in basic activities of daily living (P <
      .05), instrumental activities of daily living (P < .001), and social activity
      than control subjects (P < .05). There was no difference between the groups on
      scales measuring mental health and quality of social interaction. On mobility
      measurements, Paget's disease patients showed significant impairments when
      compared with control subjects: mobility skills protocol score (22.5 +/- 2.5 vs
      25.6 +/- 0.7, P < .001); 10-foot walk (3.96 +/- 1.3 vs 2.55 +/- 0.5 seconds, P <
      .001); 360 degree turn left (8.0 +/- 1.0 vs 5.9 +/- 0.6 steps, P < .001); and 6
      minute walk (342.0 +/- 108.5 vs 519.4 +/- 100 meters, P < .001). CONCLUSION: When
      compared with control subjects, patients who have Paget's disease of bone
      involving the tibia, femur, or acetabular portion of the ilium have clinically
      and statistically significant functional and mobility impairments compared to age
      and gender-matched controls.

PMID- 7730532
TI  - Protein-energy undernutrition and the risk of mortality within one year of
      hospital discharge: a follow-up study.
AB  - OBJECTIVE: The primary objective of this study was to confirm the results of a
      previous study that demonstrated a strong independent correlation between the
      severity of protein-energy undernutrition and the risk of 1-year postdischarge
      mortality in a population of older rehabilitation patients. DESIGN: Prospective
      survey (cohort study). SETTING: The Geriatric Rehabilitation Unit (GRU) of a
      Veterans Administration hospital. PARTICIPANTS: Of 350 randomly selected
      admissions to the GRU, 322 were discharged alive from the hospital. These 322
      patients represented the study population, of whom 99% were male, and 75% were
      white. The average age of the study patients was 76 years. MEASUREMENTS: At
      admission and again at discharge, each patient completed a comprehensive medical,
      functional, neuropsychological, socioeconomic, and nutritional assessment. After
      discharge, each subject was tracked for 1 year. MAIN RESULTS: Within the 1-year
      posthospital discharge follow-up period, 64 study subjects (20%) died. This
      included 17% of the patients discharged home and 34% of the patients discharged
      to a nursing home (P < .01). Based on the Cox Proportional Hazards survival
      model, the variable most strongly associated with mortality was the discharge
      serum albumin, followed by discharge weight expressed as a percentage of ideal,
      self-dressing ability, and a discharge diagnosis of cardiac arrhythmia (usually
      atrial fibrillation). When all four of these variables were included in the
      analysis, the model was able to differentiate the survivors from those who died
      by years end with a sensitivity of 69%, a specificity of 69%, and an overall
      predictive accuracy of 69%. When tested using the data from the previous study,
      the model differentiated the patients who died from those who had not at a
      sensitivity of 62%, a specificity of 68%, and an overall predictive accuracy of
      64%. CONCLUSIONS: Protein-energy undernutrition appears to be a strong
      independent risk factor for 1-year postdischarge mortality.

PMID- 7730533
TI  - Inappropriate use of nonpsychotropic medications in nursing homes.
AB  - OBJECTIVES: To determine the prevalence and patient-specific predictors of the
      use of 10 presumptively inappropriate medications used to treat medical
      conditions among nursing home residents, and to use this information to examine
      alternative screening strategies using computerized assessment data to identify
      residents who are at high risk of receiving inappropriate medications. DESIGN:
      Retrospective, cross-sectional study. PATIENTS: All persons residing in all 252
      nursing homes in two states during the last 6 months of 1991 (N = 21,884).
      MEASUREMENTS: Data were from Minimum Data Set Plus (MDS+) assessments, gathered
      as part of the Health Care Financing Administration (HCFA) Multistate Nursing
      Home Casemix and Quality Demonstration Project. The MDS+ is an expanded version
      of the federally mandated Minimum Data Set (MDS) that includes additional
      information on medications and their doses and schedules (frequency, standing vs
      prn). The reliability of the MDS has been demonstrated previously. Medications
      were defined as inappropriate using explicit criteria from published literature.
      Outcome measures were the standing use of each or any of 10 presumptively
      inappropriate medications used to treat medical (rather than psychiatric or
      behavioral) conditions. Potential predictors of inappropriate medication use
      included patient demographic characteristics, payer, a proxy measure for length
      of stay and admission source, functional status, number of standing medications,
      and state. MAIN RESULTS: A total of 12% of residents were prescribed one or more
      of 10 presumptively inappropriate medications on a standing basis, a figure that
      differed substantially between states (14.0% vs 7.4% (P < .001)). The most
      prevalent inappropriate medications were dipyridamole (5.4% of residents),
      amitriptyline (3.3%), and methyldopa (1.8%). Among patients receiving 0 to 3, 4
      to 6, and 7+ medications, 5%, 12%, and 19%, respectively, were receiving at least
      one inappropriate medication. In multivariate logistic regression analyses, the
      strongest predictors of inappropriate medication use were state and the total
      number of standing medications prescribed. Including other statistically
      significant predictors of inappropriate medication use (age > 65 years, never
      having been married, severe functional limitations, being a long-stay patient,
      and medical diagnosis) did not substantially improve the overall predictive
      ability of the model. CONCLUSIONS: A substantial proportion of nursing home
      residents receives presumptively inappropriate medications to treat medical
      conditions. Selecting persons prescribed large numbers of medications for further
      review may be the most efficient method for nursing home or pharmacy personnel to
      identify residents at high risk of receiving inappropriate medications. Extensive
      additional information on residents' characteristics, although widely available
      through the Minimum Data Set, does not significantly improve the ability to
      identify residents receiving inappropriate medications for medical conditions.
      State-specific policies or provider practices also influence the likelihood of
      presumptively inappropriate medication use among nursing home residents and
      deserve further investigation.

PMID- 7730534
TI  - Older nursing home residents have a cardiac arrest survival rate similar to that
      of older persons living in the community.
AB  - OBJECTIVE: To determine the survival rates of older nursing home residents after
      cardiopulmonary resuscitation (CPR) and to compare it with that of older persons
      who experienced cardiac arrest in an outpatient setting. To identify patient
      characteristics, arrest characteristics, and effort characteristics that are
      associated with higher survival rates. DESIGN: Retrospective review of emergency
      medical service charts and hospital medical records of a cohort of older nursing
      home residents (n = 114) after cardiopulmonary resuscitation and a matched cohort
      of community-residing older persons (n = 228) matched on age, gender, and year of
      cardiac arrest. SETTING: A large metropolitan city served by a tiered emergency
      medical service. MEASUREMENTS: Independent variables related to patient, cardiac
      arrest, and resuscitation effort characteristics. Dependent variables were
      defined as immediate survival after cardiopulmonary resuscitation and survival
      status at discharge. RESULTS: The mean age of nursing home residents was 80.3
      years; 62.3% were females. The majority of cardiac arrests for both groups were
      unwitnessed (67%) and had agonal rhythms (asystole and electromechanical
      dissociation). Emergency medical service efforts were similar for the two
      cohorts. Among nursing home residents, 26.3% had a return of blood pressure for
      more than 5 minutes, 70.2% were pronounced dead in the emergency room, and 10.5%
      were discharged from hospitals alive. In the matched community-residing subjects,
      22.7% had a return of blood pressure, 78.1% were pronounced dead in the emergency
      room, and 9.2% were discharged alive. Between-group comparisons of these
      variables revealed no significant differences even though our sample size was
      adequate. CONCLUSIONS: We conclude that survival after cardiac arrest of older
      persons residing in nursing homes is low; however, with an appropriate CPR/DNR
      selection process and an effective emergency medical system, survival of certain
      groups of nursing home residents following cardiac arrest could be comparable to
      that of community residing older persons. Despite the reasonably good survival
      rates for older persons seen above, our analyses indicated that patients who have
      unwitnessed arrests are not likely to survive to discharge and that patients with
      initial rhythms such as asystole or electromechanical dissociation rarely
      survive. These data suggest that patients who have an unwitnessed arrest in the
      nursing home should not receive resuscitation attempts, and in those patients for
      whom paramedics are called, resuscitation efforts should not proceed any further
      if their original rhythm is asystole or electromechanical dissociation. Thus,
      modification in nursing home policies regarding CPR efforts is needed.

PMID- 7730535
TI  - Dysphagia and dietary levels in skilled nursing facilities.
AB  - OBJECTIVE: To determine the appropriateness of dietary levels of residents with
      suspected feeding and/or swallowing disorders. DESIGN: Chart review, evaluation,
      intervention, observation. SETTING: Two skilled nursing facilities, one in
      Washington, one in Florida. SUBJECTS: Two hundred twelve residents, mean age
      72.9, suspected of having feeding and/or swallowing disorders. MEASUREMENTS:
      After documentation of dietary level, each resident on a mechanically modified
      diet was given an evaluation by a speech/language pathologist specific to their
      feeding and swallowing skills. Changes in the dietary level were made, and the
      residents were followed for 30 days to evaluate their response. RESULTS: Thirty
      one percent of the residents in the two facilities were prescribed a mechanically
      altered diet. Ninety-one percent were at dietary levels below that which they
      could tolerate safely; four percent were at dietary levels higher than they could
      tolerate; five percent were considered to be at the appropriate diet level.
      CONCLUSIONS: Many nursing home residents  may be inappropriately placed or
      maintained on mechanically altered diets. Regular reevaluation of their dietary
      level is necessary because most may be able to eat safely at higher levels.
      Active participation by speech/language pathologists knowledgeable in the
      assessment of oropharyngeal dysphagia is helpful in this process.

PMID- 7730536
TI  - Efficiency of geriatric case-finding in a private practitioner's office.

PMID- 7730537
TI  - Case management of older adults in health maintenance organizations.

PMID- 7730538
TI  - The use of expandable metal stents for large airway obstruction in older
      patients.
AB  - OBJECTIVE: To review the indications, management, and outcome of 30 older
      patients who had expandable metal stents inserted for large airway obstruction.
      DESIGN: Information was collected retrospectively from case notes about
      presentation, radiographic appearances, pulmonary function, including arterial
      oxygen tension, and histology. Survival data were collected by reviewing hospital
      or General Practice records. MEASUREMENTS: Spirometry, peak expiratory flow rate,
      and blood gases were recorded before and after stent insertion. MAIN RESULTS:
      There was a significant improvement in the patient's mean forced expiratory
      volume in 1-second (FEV1) and mean peak expiratory flow rate (PEFR). The arterial
      oxygen tension (pO2) increased from 8.6 Kpa to 10.6 Kpa. The mean length of
      survival for the whole group was just under 5 months. CONCLUSIONS: Airway
      stenting for obstruction provides palliative and functional benefits in these
      severely disabled patients and a consequent improvement in quality of remaining
      life.

PMID- 7730539
TI  - The use of the Cohen-Mansfield Agitation Inventory in the assessment of
      behavioral disorders in nursing homes.

PMID- 7730540
TI  - Feasibility and accuracy of a postcard diary system for tracking healthcare
      utilization of community-dwelling older persons.
AB  - OBJECTIVE: To test the feasibility of and to validate a self-report weekly
      postcard diary of health care utilization. DESIGN: Case-series and validation
      study. SETTING: Community-based sample of fee-for-service and health maintenance
      organization (HMO) patients. PARTICIPANTS: A convenience sample of 24 community
      dwelling older persons who had failed a self-administered screen and were
      eligible for a study of outpatient comprehensive geriatric assessment
      consultation. MEASUREMENTS: Subjects completed and mailed in a weekly postcard
      diary documenting medical, counseling, or rehabilitation therapy visits. If a
      subject did not respond within 10 days after the end of the week, a telephone
      call was placed to gather the information. For a subset of 10 subjects who were
      HMO enrollees, all records were reviewed to determine accuracy of the postcard
      diaries. RESULTS: Of the 24 subjects enrolled, one HMO enrollee dropped out
      following hip surgery after 4 weeks of completing diaries. The remaining 23
      subjects (96% of total entered) provided complete information for 12 weeks.
      Telephone follow-up to either obtain or clarify utilization information was
      required for 22% of subjects. For the subset of 10 HMO subjects, seven
      underreporting, two overreporting, and one incorrect day errors were detected-a
      total of 10 errors representing 9% of diaries and 1.3% of patient-days. Kappa as
      a measure of agreement between the two methods (self-report and chart review) was
      0.82 (P < .0001). Compared with chart review, the diary report was 75.0%
      sensitive and 99.8% specific. Positive and negative predictive values were 91.3%
      and 99.2%, respectively. CONCLUSION: These findings suggest that a postcard diary
      system with telephone follow-up is both a feasible and reasonably accurate method
      of tracking health care utilization by community-dwelling older persons, although
      a small percentage will be unable to adhere to this method.

PMID- 7730541
TI  - Framing the physician-assisted suicide and voluntary active euthanasia debate:
      the role of deontology, consequentialism, and clinical pragmatism.

PMID- 7730542
TI  - Beyond labels: nursing home care for Alzheimer's disease in and out of special
      care units.
AB  - OBJECTIVE: To compare dementia special care units (SCUs) with their non-SCU
      counterparts in terms of unit and facility characteristics. DESIGN: Cross
      sectional telephone survey and secondary database. SETTING: 1247 units in 436
      Minnesota nursing homes. MEASUREMENTS: Specialized dementia care practices (e.g.,
      staffing, environmental design and programming features) and organizational
      characteristics (e.g., size, geographic location, type of ownership, proportion
      dementia, case-mix and percentage Medicaid). RESULTS: Comparing unit level data
      for all units in 436 facilities, we found that 75 SCUs offered more dementia
      specific features than did the 1122 units not designated as SCUs, but most units
      offered some dementia-specific features similar to those of SCUs. The designation
      of SCU did not automatically translate into richer or more tailored services for
      dementia compared with units without the designation. Facilities with designated
      SCUs are more likely to be rural, larger and divided into more units, have a
      higher proportion of residents with dementia, and have fewer residents at higher
      levels of acuity. CONCLUSION: Presence of a SCU in a facility may be related to
      care of dementia in the rest of the nursing home in complex ways; some dementia
      specific features were less likely to be found in regular units of nursing homes
      with designated SCUs.

PMID- 7730543
TI  - Physician-assisted suicide and voluntary active euthanasia. AGS Ethics Committee.

PMID- 7730544
TI  - Another modifiable risk factor for cardiovascular disease? Some evidence points
      to arterial stiffness.

PMID- 7730545
TI  - Can late life social or leisure activities delay the onset of dementia?

PMID- 7730546
TI  - A half-century of delirium research: time to close the gap.

PMID- 7730547
TI  - Attempted resuscitation in nursing homes: so how should we presume?

PMID- 7730548
TI  - Can medical care improve memory in AD patients?

PMID- 7730549
TI  - Can the measurement of intraocular pressure be useful in assessing dehydration
      and rehydration?

PMID- 7730550
TI  - Methemoglobinemia toxicity from topical benzocaine spray.

PMID- 7730551
TI  - Is the phenotypic combination A1B8Cw7DR3 a marker for male longevity?

PMID- 7730552
TI  - Clinical presentation of hypothyroidism in older persons.

PMID- 7730553
TI  - Oral temperature and senile confusion: a response to Robinson.

PMID- 7730554
TI  - Myopia--a challenge to optometric research.

PMID- 7730555
TI  - RGP quality control: the results of a national survey.
AB  - BACKGROUND: Rigid gas permeable (RGP) contact lenses have numerous benefits;
      however, one of the possible problems of RGP lenses is variable quality that can
      result in reduced initial comfort and an unsuccessful fit. METHODS: A quality
      control survey was sent to 200 optometrists, selected at random, to provide
      information on lens usage, verification, use of reused or modified lenses, use of
      authorized laboratory, and to evaluate important laboratory characteristics. A
      total of 86 optometrists responded to the survey. RESULTS: The results indicated
      that most respondents fit between 10-25 percent of their new contact lens
      patients with RGPs. In addition, although both of these parameters can be
      extremely important to patient success, only 56 percent of the practitioners
      verify edge quality and even less, 38 percent, verify center thickness. Sixty
      seven percent of the practitioners indicated that poor initial wettability
      occurred in, at minimum, 5-10 percent of all new lenses. 75 percent of the
      practitioners indicated that it would matter to them if the supposed new lenses
      had previously been used or modified. Finally, optical quality and lens parameter
      accuracy were considered much more important than turnaround time and material
      cost. CONCLUSIONS: It appears from these results that variance in quality control
      can result in compromised lens quality and performance. In addition, it can be
      reduced by more careful lens inspection by the practitioner. If careful attention
      is devoted to these recommendations, RGP lens use and success could increase
      accordingly.

PMID- 7730556
TI  - Referrals by optometrists to ophtholmologists and other providers.
AB  - BACKGROUND: This study reviews 33 years of research into referrals made by
      optometrists, estimates mean referral rates and seeks to interpret what they
      mean. METHODS: A search of the medical and optometric literature, 1961-1993,
      disclosed all reports on referrals by optometrists. Techniques of meta-analysis
      were employed to rationalize results from various research designs. Principal
      variable: percent of patients referred by optometrists to 1) ophthalmologists and
      2) all providers. Mean referral rates were estimated by log-scale weighting and
      computed separately by type of practice. Also reviewed: referral rates by eye
      condition and anatomic site. RESULTS: We found 15 research studies in which
      referral rates were indicated or could be inferred. On average, optometrists
      referred 3.83 percent of their patients to ophthalmologists; 5.50 percent to all
      providers. Cataract and glaucoma were the most common conditions referred;
      anterior eye and retina the most common anatomic sites. CONCLUSIONS: No time
      trend was apparent. Referral rates varied by type of practice, with VA clinics
      high, HMOs and teaching clinics low, and private practices intermediate.
      Optometrists in private practice appear to be referring patients at rates
      consistent with referrals by optometrists who practice in more managed
      environments.

PMID- 7730557
TI  - Infiltrative keratitis with contact lens wear--a review.
AB  - BACKGROUND: "Infiltrates" of white blood cells aggregating in the superficial
      cornea are common with corneal inflammation. The etiologies of such inflammation
      vary widely and include an association with contact lens wear. METHODS: This
      paper reviews the literature regarding corneal infiltrative keratitis with
      contact lens wear. Basic mechanisms in the development of corneal infiltrates as
      well as etiologies are presented. Associations and causes, clinical presentation,
      differential diagnosis, course, and treatment for corneal infiltrates in contact
      lens wearers are reviewed. CONCLUSIONS: Corneal infiltrates associated with
      contact lens wear may stem from a variety of causes including factors related to
      the lens material, design, condition; the lens wearing schedule; environmental
      factors such as external environment; and lens care patterns, procedures, and
      products. Individuals who wear contact lenses are also subject to the many non
      contact lens-related stimuli to corneal infiltration. Accurate diagnosis and
      appropriate management of corneal infiltrates with contact lens wear is
      important, especially due to the possibility of infectious etiology.

PMID- 7730558
TI  - Men and women in optometry. I: Economic issues and professional profiles.
AB  - BACKGROUND: Optometry is experiencing a sharp increase in the number of women
      entering practice. How is this demographic shift likely to affect the profession?
      This survey was designed to describe current economic and professional profiles
      of men and women in optometry. METHODS: A survey questionnaire was mailed to a
      nationwide random sample of optometrists, equal numbers of men and women.
      RESULTS: Data were analyzed from 353 men and 356 women. Margin of error: +/- 4
      percent. On average, women optometrists are younger than men, work 9.4 percent
      fewer hours, and spend 8.1 percent more time away from their regular professional
      duties. In 1991 men's optometry income averaged $72,200; women's, $54,400. The
      income differential persisted after adjusting for age, practice setting, work
      week, time off, and specialty. Men are more likely to be in solo practice; women
      in group practice or salaried positions. Similar proportions of men and women are
      employed in corporate optometry. Few gender differences exist in patient services
      or other professional activities. CONCLUSIONS: Women optometrists have not yet
      gained economic equity with men. Male-female similarities in practice patterns
      suggest that optometry is unlikely to experience major changes in consequence of
      more women entering the profession.

PMID- 7730559
TI  - Circumscribed posterior keratoconus.
AB  - BACKGROUND: Posterior keratoconus is characterized by an internal protrusion of
      the posterior corneal surface and associated localized or diffuse stromal
      thinning. Two cases of circumscribed (localized) posterior keratoconus are
      presented that are representative of the spectrum of the anomaly. CONCLUSIONS:
      The clinical and histological appearance of posterior keratoconus and its
      differential diagnosis from other corneal ectasias and developmental anomalies
      are reviewed to enable the eye care practitioner to better diagnose and manage
      this rare anterior segment disorder.

PMID- 7730560
TI  - [Locoregional recurrences of breast cancer].
AB  - AIM OF THE STUDY: To determine the characteristics of 51 cases of isolated local
      regional breast cancer recurrence. METHODS: Retrospective study from 1980 to
      1992, survival calculated according to Kaplan-Meier and log-rank test. RESULTS:
      Twenty-five patients had had a conservative treatment of her primary tumour, 26
      had been treated by modified radical mastectomy. Local regional recurrence rate
      was 9%: 44% of recurrences after lumpectomy and 43% of recurrences after
      mastectomy occurred within 2 years after the initial treatment. Site of local
      regional recurrence was chest wall only (16 cases), breast only (15 cases) or
      axillary or supraclavicular node with or without chest wall or breast involvement
      (20 cases). The actuarial 5-year survival rate after recurrence is 54%. It
      depends on the time to recurrence (40% if time to recurrence was less than 2
      years, 68% if more than 2 years, p < 0.10), on initial node involvement (36% for
      N+, 71% for N-, p < 0.15) and on the site of recurrence (chest wall: 43%; breast:
      48%; regional node: 12%, p < 0.10). CONCLUSION: Like in the literature, severe
      recurrences are early recurrences, lymph node recurrences and recurrences
      following a primary tumour with involved axillary nodes.

PMID- 7730561
TI  - [Air embolism and exploratory hysteroscopy: myths or realities? Preliminary
      results].
AB  - OBJECTIVE: Authors tried to evaluate the prevalence of air embolism which is a
      severe complication of carbon dioxide hysteroscopy. DESIGN: On one hand, a
      retrospective inquiry with 18 hyperbaric oxygen therapy units over a 8 year
      period (1985 to 1992 included); and on the other hand, a prospective study with
      monthly survey to 84 public Gynaecology units during a 2 year period (January
      1991 the 1st to December 1992 the 31st). RESULTS: From the 18 hyperbaric oxygen
      therapy units receiving iatrogenic air embolism, gynaecologic endoscopy represent
      20% of the patients. Among these, 2/3 come from laparoscopy and 1/3 from
      hysteroscopy. In the prospective study, 42 public Gynaecology units made 5,140
      carbon dioxide hysteroscopies. Three air embolism were declared in this
      population (i.e. 0.58/1000) with 1 death and 2 recoveries without sequelae after
      hyperbaric oxygen therapy. CONCLUSION: Analysis of these cases suggest that, for
      this risk, one should oppose ambulatory hysteroscopy without anaesthesia to
      hysteroscopy under general anaesthesia with frequent cervical dilatation,
      prolonged duration and different underlying pathology.

PMID- 7730562
TI  - [Malignant non-Hodgkin's lymphoma of the cervix. A case report].
AB  - Isolated malignant non Hodgkin lymphomas (MNHL) of uterine cervix are rare, and
      the therapeutic strategy is not always clearly established. The authors report a
      case of a 78-years-old woman presenting a MNHL FIGO stage IIB and Ann Arbor stage
      IE. Extention evaluation was negative. The histologic and immunohistochemical
      examination revealed a centroblastic lymphoma type G in the Working Formulation
      (WF). The patient was successfully treated by surgery followed with combination
      chemotherapy and external radiation therapy. Intermediate grade primary MNHL of
      the uterine cervix are the most frequent. The opportunity of surgery is discussed
      because lymphoma is a general disease with blood dissemination. We propose a
      therapeutic strategy according to patient age and the wishes for pregnancy. The
      young woman could undergo polychemotherapy, perimenopausal woman a combination of
      chemotherapy and radiation therapy, and post-menopausal woman surgery followed by
      external radiation therapy.

PMID- 7730563
TI  - [Rare tumors of the cervix: three case reports: rhabdomyosarcoma, granulocytic
      sarcoma and lymphoma].
AB  - Three rare cases of tumours of the cervix are reported: embryonal
      rhabdomyosarcoma, granulocyte sarcoma and lymphoma. There were particular
      problems with diagnosis in each case requiring histochemistry,
      immunohistochemistry and ultrastructure examinations. Embryonal rhabdomyosarcoma
      is a uncommon tumour in the adult. Clinically, there is a vegetative formation
      but no botryoid aspect. Striated muscle cell proliferation, suggested by the
      morphology of the malignant cells was confirmed by immunohistochemistry which
      demonstrated desmine and vimentine and by the ultrastructural study which
      demonstrated Z lines in the cytoplasm of the malignant cells. Granulocyte sarcoma
      is characterized by a non-tumoural non-destructive infiltration of inflammatory
      like cells. Their granulocyte nature is confirmed by histochemistry, the Leder's
      reaction on frozen samples, immunohistochemistry (expression of NP57). Electron
      microscopy can also be used. The diagnosis of lymphoma is difficult due to the
      non-tumoural nature of the lymphomatous infiltration which can simulate
      inflammatory reaction. In our case, the diagnosis was made on the tumoural aspect
      of the biopsy made in the deep infiltration zone of an adjacent organ (bladder).
      Immunohistochemistry demonstrated the lymphoid nature of the tumour and
      identified a B phenotype. The ultrastructural study gave little information.

PMID- 7730564
TI  - [Cost effectiveness of methotrexate treatment of ectopic pregnancy].
AB  - OBJECTIVES: Compare the cost of managing unruptured extra-uterine pregnancy with
      methotrexate injections and with conservative laparoscopic surgery. METHODS:
      Review of the literature to quantify post-therapeutic follow-up after echoguided
      methotrexate injections or laparoscopic salpingotomy. The cost of each procedure
      was determined on the basis of the French National Health Insurance nomenclature
      (Caisse National d'Assurance-Maladie). Total costs thus induced were then
      compared. RESULTS: The cost of medical treatment for unruptured extra-uterine
      pregnancy was similar to laparoscopic surgical treatment (10,267 and 11,858 FFr
      respectively). The duration of hospitalization was short for methotrexate
      injection but the number of biology examinations required for post-therapeutic
      follow-up was greater. CONCLUSION: Cost of medical treatment and laparoscopic
      surgical treatment reported in the literature vary little. Ambulatory
      methotrexate injections and the major reduction in biology follow-up examinations
      are required for significant reduction in medical treatment costs. Rigorous
      patient selection for methotrexate treatment could both improve effectiveness and
      reduce costs. Eliminating anaesthesia-related mortality as well as any surgery
      would be the true beneficial effect of medical treatment.

PMID- 7730565
TI  - [Intramural pregnancy. A case report].
AB  - The authors present a case of intramural pregnancy diagnosed during consultation
      by endovaginal ultrasound at 7 weeks of amenorrhoea. The treatment has been
      exclusively laparoscopic and the postoperative care was uneventful.

PMID- 7730566
TI  - [Cervical pregnancy: conservative treatment with primary embolization of the
      uterine arteries. A case report. Review of the literature].
AB  - Ectopic pregnancies are rarely located in the cervix. In most (50-70%) of the
      cases, haemostatic hysterectomy is usually performed. We attempted an original
      approach for ectopic pregnancies located in the cervix which allowed preservation
      of the uterus. The uterine arteries are embolized before evacuation of the
      pregnancy and haemostasis of the loge with a balloon probe. In the literature,
      the incidence has been reported at 1 cases/20,000 births. Past history of
      curetage is a favouring factor. Echography facilitates diagnosis. When possible,
      conservative treatment may involve surgery (arterial ligature, endocervical
      haemostasis), drug therapy (methotrexate) and radiography (arterial
      embolization).

PMID- 7730567
TI  - [Sirenomelia. Review of nosology and a case report].
AB  - We report a case of sirenomelus observed at 21 weeks amenorrhoea with
      oligoamnios. This syndrome results from an anomaly during the fourth week of
      gestation perturbing development of the lower limbs and the pelvis. Normal
      differentiation of the sexual organs, urinary tract and terminal intestine is
      interrupted. Recent progress in embryopathology has led to identification of a
      caudal regression syndrome but the aetiology remains unknown as is the nature of
      the relationship with VATER association.

PMID- 7730568
TI  - [Fibromatosis found during prenatal ultrasonography].
AB  - During an antenatal echography, we observed a here to unreported fetal tumour
      which was diagnosed after birth as aggressive fibromatosis. The infant was
      treated with chemotherapy and, at the age of 27 months, still had a sclerous mass
      on the trunk which cause major scoliosis. Fibromatosis is a locally malignant
      fibrous tumour. During the unpredictable clinical course, recurrence after
      treatment as well as spontaneous regression is observed. Therapeutic management
      decisions (surgery, radiotherapy, chemotherapy) must be made on a case by case
      basis. Hormone factors and inappropriate oncogene expression are pathogenic
      factor.

PMID- 7730569
TI  - [Prenatal diagnosis of a case of Fryns' syndrome].
AB  - Fryns' syndrome was reported for the first time in 1979 in children who died
      neonatally of prematurity and respiratory distress. This lethal, autosomal
      recessive syndrome is characterized by a diaphragmatic defect, pulmonary
      hypoplasia, a "coarse" face and distal limb abnormalities. This report presents a
      prenatal ultrasonographic diagnosis at 20 weeks' gestation of a case of Fryns'
      syndrome and defines the frequency of each of its abnormalities from the 38 cases
      listed in the literature.

PMID- 7730570
TI  - [Transplacental passage of epirubicin].
AB  - We studied the transplacental transfer of epirubicin, an anthracycline used for
      the treatment of different neoplastic disorders, in particular breast cancers, by
      in vitro perfusion of term human placenta. Placenta from women with uncomplicated
      pregnancy were collected immediately after vaginal delivery and put into 37
      degrees C thermostated hood. Perfusion of foetal surface of the placenta by
      modified Earle's solution was started immediately after catheterisation at a flow
      rate of 6 ml/min and then so was the perfusion of the intervillous space at the
      rate of 12 ml/min. Samples were collected at different times after the initiation
      of the perfusion from arterial inflow and venous outflow respective of the
      maternal and foetal compartment. The transplacental transfer of epirubicin was
      investigated for two doses: 5 and 9 micrograms/ml. The mean transfer value of
      epirubicin is low (3.66 +/- 1.07%) for the two tested doses and is only slightly
      higher than doxorubicin transfer, which drug has provided rare accidents in the
      clinical reports. These results are in favour of a low placental toxicity of
      epirubicin. Clinical data have to be collected from pregnant women to confirm the
      low foetal toxicity of epirubicin.

PMID- 7730571
TI  - [Study of amniotic fluid bacterial colonization sampled by amniocentesis in cases
      with premature rupture of membranes. Prospective multicenter study].
AB  - OBJECTIVE: To determine the relationship between bacterial colonization of the
      amniotic fluid sampled by amniocentesis and premature rupture of the membranes.
      METHODS: A prospective multicentric study conducted over a one year period in 6
      maternity wards in the suburban area of Paris. Thirty-six women with premature
      rupture of the membranes were studied. RESULTS: There were 11 patients (30%) with
      contaminated fluid at the first amniocentesis. Twenty-five patients had sterile
      fluid. In 7 patients with prolonged rupture for more than one week, repeated
      amniocentesis. Twenty-five patients had sterile fluid. In 7 patients with
      prolonged rupture for more than one week, repeated amniocenteses were used to
      follow bacterial colonization. In one patient, Proteus mirabilis in the amniotic
      fluid was eradicated by adapted antibiotic therapy. In patients with sterile
      amniotic fluid, there was no secondary colonization. In the 11 cases with
      colonized liquid, the vaginal swab could only be considered as positive in 4
      cases. Amniocentesis was able to discover 7 bacterial colonizations of the
      amniotic fluid in patients with an indeterminant vaginal swab. Likewise, C
      reactive protein levels were raised only in 26% of the cases with a colonized
      amniotic fluid.

PMID- 7730572
TI  - [History of the Federation of French Speaking Gynecologists and Obstetricians].

PMID- 7730573
TI  - [Intrepretation of elevated transaminase levels in a pregnancy after a liver
      transplantation].
AB  - A young woman became pregnant 36 months after a liver transplant following an
      episode of fulminant hepatitis A. At 38 weeks gestation, she delivered by
      cesarean section following an isolated and moderate elevation of her transaminase
      enzymes, indicating rejection of the graft. This was later confirmed by liver
      biopsy. Following augmentation of steroid therapy her postnatal progress was
      good. The infant progressed quite well. This case raises the question of the
      management of pregnant women following liver transplantation, with elevated
      transaminase levels.

PMID- 7730574
TI  - [Tubular sterilization in the immediate postpartum period using local anesthesia
      and laparoscopy].
AB  - Puerperal laparoscopic sterilization was performed in 732 women under anaesthesia
      at the Maternity of Noumea (New-Caledonia). There were no complications. Among
      the per-operative and postoperative incidents which occurred, there were 0.8%
      pregnancies, 3.6% bleeding of the broad ligament which was controlled during
      laparoscopy and 3% events (adhesion, pain) which required general anaesthesia. It
      was concluded that the described technique of puerperal laparoscopic
      sterilization is a safe, simple, rapid, inexpensive and reliable surgical
      technique in expert hands.

PMID- 7730575
TI  - [Prenatal diagnosis of homozygous pyruvate kinase deficiency].
AB  - Two consecutive cases of severe neonatal anaemia due to severe deficiency in
      pyruvate kinase were observed in the same sibhood. The first child died one hour
      after birth and the second required major transfusion support. Pyruvate kinase
      deficiency is a rare cause of congenital anaemia with recessive autosomic
      inheritance. Clinically, this deficiency has a very variable expression, and
      neonatal forms are not always very severe. Several variant molecules in pyruvate
      kinase deficiency have been described. Recent progress in our understanding of
      the gene would suggest the possibility of new diagnostic and prognostic
      approaches.

PMID- 7730576
TI  - [Breast cancer after treatment of Hodgkin's disease].
AB  - OBJECTIVES: Development of diagnostic, therapeutic and preventive measures for
      breast cancer after cure of Hodgkin disease. STUDY TYPE: Presentation of 4
      patients treated conjointly by the Radiotherapy and Gynaecology Surgery
      Departments of the Rennes University Hospital. RESULTS: Illustrations of
      difficult management of breast cancer at different stages of diagnosis and
      therapy. CONCLUSION: A past history of treated Hodgkin disease is a factor of
      risk for breast cancer and suggests the need for annual mammography screening 10
      years after the end of treatment. Though more difficult, mastectomy is
      recommended over conservative radiosurgical treatment. The choice of drugs for
      adjuvant chemotherapy should rely on Hodgkin protocols and take into account
      heart function. Long-term carcinogenic effects of Hodgkin disease treatments
      requires modulation of the different treatment protocols as a function of stage,
      clinical and histological factors of prognosis and patient age.

PMID- 7730577
TI  - [Uterine rupture at 22 weeks gestation due to placenta praevia percreta].

PMID- 7730578
TI  - Group intervention: the healing journey of incest.
AB  - Nurse-facilitated, long-term group intervention provides a healing environment
      for adult survivors of incest. In this article, the healing journey of the group
      process is discussed as two clinical specialist nurse facilitators share their
      experiences of facilitating long-term incest groups for the past 5 years at a
      nurse-managed center for practice in the college of nursing at a large midwestern
      university. The group intervention, which consists of 51 sessions 1 1/2 hours in
      length, is discussed in depth. The three phases of the group and the tasks of
      each are developed in detail in relation to the mind-body-spirit healing that
      occurs. Use of clinical vignettes elaborates the group experiences and the
      healing evolution of the group members.

PMID- 7730579
TI  - Victims of family abuse: the need for spiritual healing.
AB  - This article describes a short-term group offered to adult abuse survivors to aid
      in spiritual healing. The terms spiritual and spiritual distress are defined, the
      group format is delineated, and the need for all nurses to develop spiritual
      awareness when working with clients with family abuse histories is stated.

PMID- 7730580
TI  - A practical approach in the treatment of self-inflicted violence.
AB  - After a brief review of the literature on self-inflicted violence, a practical
      approach to the treatment of patients who show self-injurious behavior and self
      mutilation is developed. The treatment model uses therapeutic interventions based
      on a biopsychosocial understanding of the person and applies knowledge from the
      biological, psychological-behavioral, and social fields. Interventions discussed
      include ego strengthening, planning for substitute behaviors, therapeutic
      imagery, ego-state therapy, reframing, cognitive syllogism, behavioral
      reinforcement and extinction, and use of behavioral contracts. The case examples
      presented illustrate the importance of the therapist/patient relationship, which
      is based on trust, respect, and caring but also on patient responsibility for
      change.

PMID- 7730581
TI  - Healing the effects of violence.

PMID- 7730582
TI  - Domestic violence: a nursing imperative.
AB  - This manuscript describes female partner abuse and reviews its significance to
      health care providers. Attention is given to the essential nursing roles of
      screening for abuse, intervening with women at risk for abuse, and completing a
      needed examination when abuse has occurred. Ideas for an expanded nursing role
      are provided.

PMID- 7730583
TI  - Incest/child sexual abuse: historical perspectives.
AB  - After identifying that social scientists and historians have long believed (and
      vigorously defended) that the only universal trait found in every known culture
      is the prohibition against incest, occurrence of incest and child sexual abuse is
      traced first through Western culture from antiquity to the present with special
      emphasis on Sigmund Freud's "reversal." It then is traced through Eastern culture
      from ancient to modern times. Contemporary trends of self-disclosure of incest
      and child sexual abuse are examined, and current incidence data are provided. The
      backlash phenomenon is then explored, and conclusions are drawn.

PMID- 7730584
TI  - Domestic violence: myths and safety issues.
AB  - After providing incidence data, identifying stereotypes, and defining abuse, this
      article discusses domestic violence in the context of patterns of covert and
      overt control rather than looking at isolated incidents of battering. Ways to
      assess the likelihood of an emergency room or a doctor's office visit being the
      result of domestic violence are outlined as well as methods of assessing the
      degree of immediate danger to the woman.

PMID- 7730585
TI  - Dramatic heterogeneity of transgene expression in the mammary gland of lactating
      mice: a model system to study the synthetic activity of mammary epithelial cells.
AB  - We studied the expression of human serum albumin (HSA) driven by the ovine beta
      lactoglobulin promoter in the mammary glands of lactating mice from five
      independent transgenic strains, by employing combined in situ hybridization and
      immunostaining techniques. Four strains displayed a heterogeneous pattern of
      expression: mice of strains 91 and 92 expressed the transgene in only a fraction
      of the lobules, whereas in strains 69 and 83 all lobules contained cells
      expressing HSA. In all four strains the patterns of expression within expressing
      lobules corresponded to the morphology of alveolar cells and to the extent of
      local milk secretion, suggesting that filling of alveolus with secreted material
      was accompanied by asynchronous downregulation of transgene expression. In situ
      hybridization to the endogenous milk protein genes alpha-lactalbumin, beta
      casein, and whey acidic protein revealed a uniform pattern of expression in
      lactating mammary glands of transgeneic and in four out of five non-transgeneic
      mice. In the fifth control mouse, we detected downregulation of gene expression
      in lobules containing alveoli distended by secreted milk. The pattern of
      expression of the three endogenous genes was greatly disturbed after a short (3
      hr) unilateral closure of mammary glands, and very much resembled the pattern of
      expression of the HSA transgenes. These results demonstrate that transgeneic mice
      provide a useful model to study the factors that regulate the synthetic activity
      of mammary epithelial cells.

PMID- 7730586
TI  - Quantification of ANP mRNA in primary cultures of adult rat atrial myocytes by
      image processing: in situ hybridization to multiple parallel samples using single
      stranded cDNA probes.
AB  - In primary cultures of adult rat atrial myocytes, we quantified the accumulation
      of atrial natriuretic peptide (ANP) mRNA in parallel with ANP secretion. ANP mRNA
      was quantified by image analysis of myocytes hybridized in situ with single
      stranded cDNA probes generated by two successive thermal cycling procedures. In
      situ analysis permitted measurement of many small experimental samples in tandem
      while avoiding the possibility of differential extraction and processing of mRNA
      from sample to sample. The single-step application of 32P-labeled probes allowed
      processing of many parallel samples and generated intense punctate
      autoradiographic signals that were readily countable by image processing. Biotin
      labeled probes, in conjunction with gold-labeled anti-biotin antibodies and
      silver intensification, gave an apparently equivalent specific signal but
      presented more difficulty in uniform processing of many samples and was harder to
      quantify by our image processing system. Measurement of ANP mRNA during atrial
      myocyte culture showed that ANP mRNA accumulated from undetectable levels after 1
      day of culture to maximal levels by Day 8. In contrast, secretion of ANP (which
      is stored in atrial granules) slowly decreased, but was not abolished, during the
      first 5 days of culture. Subsequently, ANP secretion increased, with the increase
      trailing ANP mRNA accumulation by at least 24 hr.

PMID- 7730587
TI  - Co-injection of wheat germ agglutinin-HRP and choleragenoid-HRP into the sciatic
      nerve of the rat blocks transganglionic transport.
AB  - We report on the surprising loss of transganglionic and retrograde labeling in
      the spinal cord of the rat after co-injection of the tracers wheat germ
      agglutinin-HRP (WGA-HRP) and choleragenoid toxin-HRP (CTB-HRP) into the sciatic
      nerve. Injection of WGA-HRP alone produced a pattern of transganglionic label
      consistent with transport by small-diameter primary afferent fibers. Small cell
      bodies were labeled in the ipsilateral dorsal root ganglion (DRG) and there was
      dense terminal labeling in the superficial dorsal horn of the lumbar spinal cord.
      Injection of CTB-HRP alone produced a pattern of transganglionic labeling
      consistent with transport by large-diameter primary afferent fibers. Large cell
      bodies were labeled in the DRG and there was dense terminal labeling in the
      nucleus proprius (Laminae III-V) in the spinal cord. CTB-HRP also produced
      extensive retrograde labeling of ventral horn motor neurons. When the two tracers
      were co-injected, we found few labeled cells in the ipsilateral DRG and there was
      almost complete loss of transganglionic terminal labeling in the lumbar spinal
      cord. Retrograde labeling of motor neurons was also significantly reduced. Even
      when one of the tracers (e.g., WGA-HRP) was injected 24 hr after and up to 10 mm
      proximal to the site of the first tracer (e.g., CTB-HRP), an inhibitory
      interaction was detected. The labeling pattern was always characteristic of the
      first tracer injected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730588
TI  - Dopamine D1 receptor distribution in Sf9 cells imaged by confocal microscopy: a
      quantitative evaluation.
AB  - A c-myc epitope-tagged human dopamine D1 receptor (c-myc D1 receptor) was
      expressed in Sf9 cells and its cellular distribution under basal conditions and
      after exposure to the agonist dopamine was examined. In the basal state,
      immunofluorescently labeled c-myc D1 receptors imaged by confocal microscopy
      appeared as a bright ring of label predominantly on the cell surface, and to a
      lesser extent as intracellular clusters of label. This pattern of receptor
      distribution was confirmed by radioligand-binding assays on plasma membrane and
      light membrane fractions using the D1 receptor-antagonist [3H]-SCH-23390. After
      exposure to dopamine, c-myc D1 receptors were redistributed on the cell surface,
      changing from a continuous ring to a discontinuous pattern of label. Analysis of
      fluorescence intensity and three-dimensional computer reconstruction of labeled
      receptors revealed a 30% decrease in surface labeling with no decrease in total
      number of receptors confirmed by radioligand-binding analysis. These findings
      constituted the first direct evidence of agonist-induced D1 receptor
      internalization. The results showed that the combination of confocal microscopy
      and three-dimensional reconstruction can be used to visualize and assess receptor
      distribution in Sf9 cells.

PMID- 7730589
TI  - Low-fading immunofluorescence with propidium iodide contrast compared with
      immunogold light microscopy in whole cells and semi-thin cryosections.
AB  - Conventional immunofluorescence produces excellent labeling but has drawbacks
      such as fading and the need for phase-contrast. Silver-enhanced colloidal gold
      probes allow counterstaining and permit permanent preparations with no fading if
      mounted correctly, but the most common limits of this technique are steric
      hindrance and the artifacts produced by silver enhancement. Our goal was to
      investigate Herpes simplex virus type 1 (HSV-1) morphogenesis by immunogold
      cryosection electron microscopy. We therefore needed a sensitive and reproducible
      immunocytochemical light microscopic method to confirm the immunofluorescence
      results in whole cells and to screen the cryopreparations before the time
      consuming electron microscopic studies. We report data showing that the use of p
      phenylenediamine to retard fading and propidium iodide to provide counter
      staining results in brilliant fluorescence and contrast, minimal
      autofluorescence, and invisible fading at least for 5 min exposures, even in
      preparations with weak antigen presentation. Storage at -20 degrees C provides
      stable fluorescence. This method is superior to silver-enhanced colloidal gold
      light microscopy in our investigations.

PMID- 7730590
TI  - Rapid primary microwave-aldehyde and microwave-osmium fixation: improved
      detection of rat parotid acinar cell secretory granule alpha-amylase using a post
      embedding immunogold ultrastructural morphometric analysis.
AB  - Studies of methods for improved fixation are becoming increasingly important in
      the field of quantitative immunocytochemistry. We used microwave (MW)-assisted
      chemical fixation to show improved retention of salivary gland acinar cell
      secretory granule alpha-amylase detected by a quantitative immunogold method.
      Blocks (4-mm3) of rat parotid gland were fixed by the following methods: (a) MW
      irradiation in an aldehyde fixative (AF) for 6 sec; (b) immersion in AF for 1.5
      hr; (c) MW irradiation in osmium tetroxide (OT) for 9 sec; (d) immersion in OT
      for 1.5 hr; or (e) Sequential MW AF, 10 sec, MW OT rapid treatment (SMAORT), 10
      sec. Specimens were processed routinely for transmission electron microscopy.
      Thin sections of Epon-embedded tissues were exposed first to rabbit IgG anti
      human salivary alpha-amylase and second to gold-conjugated goat anti-rabbit IgG.
      Granule area was obtained by a point counting method. Labeling density was
      calculated as the number of gold particles/micron 2 +/- SD. Specimens fixed in
      seconds by MW-AF, MW-OT, or SMAORT showed ultrastructural preservation similar to
      immersion fixation in AF or OT for 1.5 hr. Immunogold labeling density of granule
      alpha-amylase was highest for SMAORT (874 microns 2) compared to MW-AF (295
      microns 2), MW-OT (248 microns 2), routine sequential immersion in AF and OT (229
      microns 2), or immersion in OT (no aldehyde) (190 microns 2). This study
      establishes the improved retention of salivary gland acinar cell secretory
      granule alpha-amylase and markedly enhanced fixation speed for ultrastructural
      studies made possible by MW-chemical fixation protocols that use aldehydes and
      osmium.

PMID- 7730591
TI  - The septoclast, a cathepsin B-rich cell involved in the resorption of growth
      plate cartilage.
AB  - At the transition between growth plate cartilage and the endochondral bone
      region, transverse septa are being eroded to allow the advance of invasive
      capillaries. To find out whether resorption is due to proteinase activity, tissue
      sections prepared from the growth plate/metaphyseal interface of young rats were
      immunostained with antibodies to the cysteine proteinase cathepsin B. Intense
      staining was found in a cell that is associated with the growing portion of the
      invasive capillaries and extends between them and the transverse septum. This
      cell has a single nucleus, actively synthesizes protein, and shows two other
      characteristic features: the cytoplasm is packed with multivesicular and dense
      bodies rich in cathepsin B, and the cell apex ends in a ruffled border extending
      into the transverse septum and signs of dissociated extracellular matrix. Even
      though the ruffled border resembles that of the osteoclast, the cell was not
      immunostained by a monoclonal antibody that recognizes a 97 KD protein known as
      ED1 which characterizes rat osteoclasts, monocytes, and macrophages. Therefore,
      this distinctive cell produces the proteinase cathepsin B and appears to be
      involved in the resorption of the transverse septum. The cell has been named the
      "septoclast."

PMID- 7730592
TI  - Cytochemical application of tris (2,2'-bipyridine) ruthenium (II): fluorescence
      reaction with sulfated polyanions of mast cell granules.
AB  - We describe the use of tris (2,2'-bipyridine) ruthenium (II) (Rubipy) as a
      cationic fluorochrome for cytochemical and histochemical studies. After staining
      with Rubipy, mast cell granules (MCGs) and lymphocyte nuclei (LN) from mouse
      peritoneal cavity and human breast carcinoma showed intense orange fluorescence
      and no fading under blue or blue-violet exciting light. Staining at low pH (< 2)
      or pre-treatment with Al3+ ions strongly diminished the fluorescence of LN,
      whereas that of MCG was less affected. Ca2+ and Ba2+ ions only diminished MCG
      fluorescence. Blots of DNA, pectic acid, heparin, and other sulfated
      polysaccharides stained with Rubipy showed high emission, which was reduced in
      DNA and pectic acid staining at low pH. Studies with chemically modified heparins
      suggested that O-sulfates were more important than N-sulfates in Rubipy-heparin
      interactions. These results are in agreement with an ionic binding mode between
      Rubipy and heparin. A very suitable method for mast cell detection was found with
      Mayer's hematoxylin before Rubipy staining, which could be of great value for
      histopathological studies. This procedure allowed visualization of the mast cells
      by fluorescence microscopy, and nuclei and tissue morphology were easily
      visualized under brightfield illumination.

PMID- 7730593
TI  - Differential expression of cathepsins B and D in testis and epididymis of adult
      rats.
AB  - Cathepsins are specific proteases in lysosomes that participate in the
      degradation of proteins, some of which are derived from endocytosis. In this
      study we examined the immunocytochemical localization of cathepsin B and D
      antibodies in cells of rat testis and epididymis, using light and electron
      microscopic immunocytochemistry. In testis, cathepsin D was immunolocalized over
      lysosomes of Sertoli cells and Leydig cells and on the acrosome of spermatids.
      Cathepsin B was found over lysosomes of macrophages. Non-ciliated cells of the
      efferent ducts revealed intense immunogold labeling over lysosomes with both anti
      cathepsin B and D antibodies. In epididymis, cathepsins B and D showed marked
      variations in expression over the different epithelial cells and regional
      differences for a given cell type. Anti-cathepsin D antibodies showed intense
      labeling over lysosomes of principal cells in the corpus and proximal cauda. In
      contrast, anti-cathepsin B antibodies revealed intensely labeled lysosomes of
      principal cells of the distal initial segment, intermediate zone, and caput
      epididymidis, with weaker labeling in other regions. Clear cells of the proximal
      caput epididymidis revealed intensely labeled lysosomes for anti-cathepsin D
      antibodies. In the distal caput, clear cells showed a variable reaction pattern
      from intensely labeled to unreactive. Basal cells of teh intermediate zone and
      proximal caput region were intensely reactive for anti-cathepsin D antibodies.
      There was no staining over clear or basal cells with anti-cathepsin B antibodies.
      Taken together, these results demonstrate cell-specific and regional differences
      in the distribution of cathepsins B and D in cells of the male reproductive
      system. Such results suggest substrate specificity with regard to protein
      turnover within lysosomes of cells of testis and epididymis.

PMID- 7730594
TI  - Cytochrome P-450 reductase content in rat liver sections by quantitative
      immunohistochemistry with video image processor.

PMID- 7730595
TI  - Psychophysically acceptable weights for a combination lifting task using bags
      with handles.
AB  - This paper presents a study on a combination lift and lower manual handling task
      and was designed to simulate the loading of grocery bags into a car trunk. Twelve
      male subjects performed an externally paced task of lifting grocery bags loaded
      with weights from 15 cm above the floor and over a wooden sill. There were two
      different sill heights of 70 cm and 90 cm, and for each of these heights there
      were two frequencies of 3 and 6 lifts per cycle. The dependent variables were
      maximum acceptable weight of lift (MAWOL). A unique lifting sequence and a
      modified version of the psychophysical methodology were used to determine MAWOL.
      There was a significant difference in the MAWOL across the two sill heights as
      well as the MAWOL at the two different frequencies. Plastic bags were determined
      to increase the average load lifted by 27% as compared to paper bags. At normal
      grocery bag weights, the increased load carrying capacity represents an increase
      in the safety factor. Not only can the risk of lower back injuries be decreased
      by using plastic bags with handles but the risk of developing a cumulative trauma
      disorder could also be decreased.

PMID- 7730596
TI  - Effects of different patterns of stairclimbing on physiological cost and motor
      efficiency.
AB  - The purpose of the present study was to investigate the effects of different
      motion patterns of ascending and descending stairs on oxygen consumption (VO2),
      heart rate (HR) and efficiency. Five healthy males performed ascending and
      descending by two motion patterns; climbing foot over foot (usual climb) and
      climbing with both feet on each step (stepping climb), at the stepping rates of
      25, 37, 50, and 62 steps.min-1. The results showed that VO2 and HR were
      significantly higher (on average 10%) with the stepping climb than the usual
      climb, and the difference between them tended to increase in proportion to the
      stepping rates. HR values to VO2 in the stepping climb significantly higher than
      those in the usual climb at each stepping rate during stair ascent and descent.
      In terms of motor efficiency and efficiency of locomotion (kcal.step-1.kg-1) the
      usual climb was more efficient than the stepping climb during stair descent and
      ascent. These results suggested that usual climb has the advantages of lower
      physiological cost and higher efficiency than the stepping climb with increasing
      the stepping rate. Furthermore, the effects of motion patterns during stair
      descent were less than those during ascent.

PMID- 7730597
TI  - Desynchronization of circadian rhythms in a group of shift working nurses:
      effects of pattern of shift rotation.
AB  - Sixteen shift working nurses, (eight senior and eight junior nurses) working in a
      Government hospital and five diurnally active healthy human subjects participated
      in the present study. The subjects self-measured oral temperature, heart rate,
      subjective fatigue, subjective drowsiness, finger counting speed and random
      number addition speed 4-6 times a day for about 3 weeks. Power spectrum and
      cosinor techniques were employed to analyze individual and group time series. The
      frequencies of circadian rhythm detection, by cosinor rhythmometry as a group
      phenomenon, were of 100%, 38%, and 21% in control subjects, senior nurses and
      junior nurses, respectively. These results were also complemented by power
      spectrum analysis. Desynchronization of circadian rhythms in several variables
      was documented in shift workers. The extent of desynchronization was more
      prominent among junior nurses as compared with their senior counterparts. It was
      also noticed that in several variables frequency multiplication of circadian
      rhythm took place among shift workers. The differences in terms of shift-work
      effects ranging from rhythm desynchronization to frequency multiplication between
      senior and junior nurses could be ascribed to the pattern of shift rotation
      employed.

PMID- 7730598
TI  - The back compressive forces during maximal push-pull activities in the sagittal
      plane.
AB  - Ten normal young male and ten normal young female subjects (each group with a
      mean age of 21.1 years) performed isometric and isokinetic (50 cm per second)
      push and pull activity at 35 cm, 100 cm and 150 cm heights. The subjects were
      placed on a specially designed subject-stabilizing-platform to stabilize their
      lower extremities. Horizontal push-pull forces were exerted through a friction
      reduced rod and sleeve assembly attached to the modified Static Dynamic Strength
      Tester. The strength measured by a SM 500 load cell was fed to an IBM XT through
      an A to D converter. The postural records were made on a videotape. The posture
      and strength were synchronized through an external light signal. The strength for
      pull activities was higher than the corresponding push activities (p < 0.01). The
      isometric strengths were significantly higher than the isokinetic strengths (p <
      0.01). Though the push strengths were significantly lower than the pull strength,
      the low-back compressive forces for the push activities were 129% to 627% of the
      corresponding pull conditions. It is concluded that the push activities are more
      hazardous due to the higher magnitude of compressive load and their faster
      contribution to the threshold level of cumulative load leading to the
      precipitation of injuries.

PMID- 7730599
TI  - Characteristics of the health conditions of old patients with spinal cord injury.
AB  - The state of health of old patients with spinal cord injury (SCI) was
      investigated to clarify the disorders that they are presently suffering from. A
      questionnaire was sent by mail to 668 patients with SCI living in western Japan.
      Valid answers were returned from 448 (67%), and they were divided into a young
      group (160 patients aged 18-39 years), middle-aged group (193 patients aged 40-59
      years), and elderly group (95 patients aged 60-73). About 30% in the young group
      answered that they were ill or worrying about their health. This percentage was
      about 60% in the middle-aged and elderly groups. According to disease types, none
      of the young group had urological diseases except urological impairment or
      cardiovascular diseases, but many of the elderly group had urological tract
      infection, kidney diseases, cardiovascular diseases, and digestive diseases.
      Decubitus ulcer was reported in all groups. Urological diseases and decubitus
      ulcer were considered to be characteristic ailments of individuals with SCI. The
      elderly group was also characterized by a high incidence of adult diseases such
      as hypertension and diabetes mellitus. Therefore, the types of diseases and their
      frequency are considered to be different in older patients with SCI compared with
      the aged population in general because of the characteristic conditions of SCI in
      addition to adult diseases.

PMID- 7730600
TI  - Reproducibility of VO2-VCO2 relationship during incremental exercise protocol.
AB  - We examined the effect of two different slope protocols to the reproducibility of
      the VO2-VCO2 relationship and the lactic acidosis threshold (LAT) during
      incremental exercise. Two adult male subjects performed a cycle ergometer
      exercise 2 to 4 times repeatedly in which the increase of work rate was 25 W
      every 1 or 2 min according to experimental design method. Gas exchange parameters
      during each exercise was measured every 10 s. The V-slope method was applied to
      the data which remained after the deletion of the data during the transient phase
      with the onset of exercise and above respiratory compensation of metabolic
      acidosis (RCMA), for detecting LAT and summarizing the VO2-VCO2 relationship
      below and above LAT. LAT had a high reproducibility whichever slope protocol was
      used. The confidential limit of LAT estimated by a statistical method was about
      +/- 0.1 l/min in terms of VO2. There were stable and reasonable responses of VO2
      VCO2 during incremental exercise in which the work rate increased 25 W every 1
      min.

PMID- 7730601
TI  - Maximum acceptable frequencies for females performing a drilling task in
      different wrist postures.
AB  - This paper presents a study on the effect of wrist posture; flexion, extension,
      ulnar deviation, and radial deviation on maximum acceptable frequencies (MAF) for
      a drilling task using a psychophysical approach. Twelve females were selected
      from a college population to serve as subjects and an adjustable workstation was
      used to simulate a drilling task. The results revealed that flexion, extension,
      and radial deviation all had a significant effect on MAF but, ulnar deviation did
      not. The postures have been ranked in order of possible risk of contributing to
      CTD injury, with neutral having the lowest rank (lowest risk) and flexion having
      the highest rank (greatest risk).

PMID- 7730602
TI  - The improvement effect of Modern Balinese Baris Dancing Exercise on body
      composition, blood pressure and heart rate.
AB  - Sixty healthy males, adult Balinese, aged from 18 to 22 years old, were studied
      to estimate the effect of Modern Balinese Baris Dancing Exercise (MBBDE) on body
      composition, heart rate, and blood pressure at rest. Based on their physical
      fitness level, the subjects were divided into an experimental group (EG) and a
      control group (CG). The EG had 8 weeks of practicing the MBBDE which consisted of
      73-87% of estimated maximum heart rate level, 3 x 50 min per week. Significant
      reductions in fat tissue weight (-0.25 +/- 0.22 kg in EG and -0.02 +/- 0.51 kg in
      CG; p < 0.05), and percent body fat (-0.53 +/- 0.37% in EG and -0.20 +/- 2.05% in
      CG; p < 0.05) were found after 8 weeks of exercise. This exercise also
      significantly reduced systolic blood pressure (-7.1 +/- 6.78 mmHg in EG and -1.8
      +/- 4.63 mmHg in CG; p < 0.001), diastolic blood pressure (-4.5 +/- 5.14 mmHg in
      EG and -0.5 +/- 3.03 mmHg in CG; p < 0.001), and mean blood pressure (-5.3 +/-
      5.96 mmHg in EG and -0.9 +/- 3.83 in CG; p < 0.001) at rest. There was also a
      significant reduction in resting heart rate (-8.8 +/- 6.42 bpm in EG and -2.2 +/-
      4.82 bpm in CG; p < 0.001). It is concluded that 8 weeks of practicing the MBBDE
      improved body composition and cardiovascular function as well.

PMID- 7730603
TI  - Apoptosis: O death, where is thy sting?

PMID- 7730604
TI  - Peptide and protein antigens require distinct antigen-presenting cell subsets for
      the priming of CD4+ T cells.
AB  - Priming of naive CD4+ T cells to Ag requires an antigen-presenting cell (APC)
      that can take up the Ag and present peptide bound to MHC class II molecules. We
      have used both in vivo and in vitro approaches to demonstrate that the APC used
      to prime naive CD4+ T cells depends on the initial form in which an Ag is
      administered. Although Ag delivered as a peptide was presented most efficiently
      to CD4+ T cells by DC, these APC were poor at priming to a protein form of the
      same Ag. In contrast, the presence of B cells was a requisite for priming to
      protein Ag.

PMID- 7730605
TI  - Heavy chain V gene-specific elimination of B cells during the pre-B cell to B
      cell transition.
AB  - As developing B cells acquire their surface Ig (sIg) receptors, they become
      highly susceptible to sIg-mediated negative selection, a process best exemplified
      by tolerance induction. Recent studies with sIg transgenic mice have suggested
      that B cells may become inactivated by tolerogens only after a developmental
      stage wherein they express low levels of sIgM and during the course of up
      regulating their expression of sIgM. To determine whether inactivation of B cells
      of conventional mice occurs at this or other maturational stages, we have
      analyzed the ratio of productive vs nonproductive rearrangements of VH81X gene
      segments in developmental subsets of adult bone marrow cells. Earlier studies had
      demonstrated that cells whose productively rearranged H chain V region contained
      a VH81X gene segment were selectively disfavored both during pre-B cell
      development and subsequent to sIg expression. Contrary to the expectations for
      elimination by tolerance, no decrease in the proportion of cells expressing
      productive rearrangements of VH81X was observed as cells matured from the sIgMlow
      to the sIgMhigh maturational stage. However, a significant decrease in the
      proportion of productively rearranged VH81X gene segments was observed following
      the transition from sIg- pre-B cells to sIgMlow immature B cells. Additionally,
      the proportion of productively rearranged VH81X gene segments was significantly
      higher in sIgMhigh bone marrow cells than in splenic B cells. These findings
      demonstrate that B cells are susceptible to H chain-specific elimination at two
      developmental stages other than that wherein B cells are generally assumed to be
      negatively selected by tolerance.

PMID- 7730606
TI  - cAMP-independent effects of cholera toxin on B cell activation. III. Cholera
      toxin A subunit-mediated ADP-ribosylation acts synergistically with ionomycin or
      IL-4 to induce B cell proliferation.
AB  - To investigate whether ADP-ribosylation of proteins by cholera toxin could
      influence B cell activation, B cells were incubated with the A subunit of cholera
      toxin. Ionomycin acted synergistically to induce B cell proliferation with the A
      subunit of cholera toxin but not with cAMP-enhancing agents or with the B subunit
      of cholera toxin, suggesting that the synergistic effect of the A subunit was
      mediated via ADP-ribosylation and not via cAMP elevations or ganglioside GM1
      binding. Indeed, inhibitors of ADP-ribosylation blocked the synergistic effect.
      Unlike anti-Ig, B cell proliferation stimulated by LPS or by the combination of
      the A subunit and ionomycin was observed in protein kinase C (PKC)-depleted B
      cells. However, neither the A subunit nor ionomycin enhanced B cell proliferation
      stimulated by low dose LPS, suggesting that the A subunit plus ionomycin
      stimulated an activation pathway distinct from the LPS-stimulated pathway.
      Additionally, unlike LPS, the A subunit plus ionomycin did not stimulate B cells
      in vitro to secrete Ig. IL-4 acted synergistically with the A subunit to induce B
      cell proliferation to the same extent as it did with anti-Ig; unlike the anti-Ig
      plus IL-4 synergy, however, the A subunit plus IL-4-mediated synergy persisted in
      PKC-depleted B cells. Taken together, our data suggest that cholera toxin A
      subunit-catalyzed ADP-ribosylation modifies a non-Gs protein involved in the
      activation of B cells, either through a novel pathway or at a point distal to the
      activation of PKC along the anti-Ig-stimulated pathway.

PMID- 7730607
TI  - Nerve growth factor induces activation of MAP-kinase and p90rsk in human B
      lymphocytes.
AB  - A previous report from this laboratory demonstrated that human B lymphocytes
      expressed nerve growth factor (NGF) receptors on their surface. On the basis of
      NGF enhancement of B cell proliferation these receptors are presumed to be
      functional. We have now characterized one of the signaling pathways that NGF may
      utilize in the functional activation of B lymphocytes. Stimulation of three
      different human B-lymphoblastoid cell lines with NGF induced the tyrosine
      phosphorylation and activation of the p42erk-2 isoform of MAP-kinase (MAPK). In
      addition, NGF induced shifts in the mobility of p90 ribosomal S6 kinase (p90rsk)
      on immunoblots and increased p90rsk kinase activity in immunoprecipitates. NGF
      induced shifts in p90rsk mobility displayed similar dose and time kinetics as NGF
      induced MAPK activation. Activation of both MAPK and p90rsk occurred with doses
      of NGF as low as 400 pg/ml. Preincubation of NGF with anti-NGF Ab inhibited NGF
      induced activation of MAPK and p90rsk. These results demonstrate that the
      interaction of NGF with its receptor on human B cells results in the stimulation
      of major components of the signaling pathway also initiated by NGF-receptor
      ligation in cells of neuronal origin.

PMID- 7730608
TI  - In vitro maturation of clonal CD4+CD8+ cell lines in response to TCR engagement.
AB  - Engagement of the TCR on immature CD4+CD8+ (DP) thymocytes by an appropriate
      peptide/MHC ligand evokes a complex program of maturation known as positive
      selection. As a result, DP thymocytes are rescued from programmed cell death,
      become committed to the CD4 or CD8 lineage, extinguish expression of V(D)J
      recombinase activity, and undergo further maturation. We describe here a panel of
      DP thymic lymphoma cell lines that, in response to in vitro TCR engagement,
      undergo many of the TCR-beta-induced maturation events that have been reported to
      accompany positive selection of DP thymocytes in vivo. These events include
      increased expression of CD5, CD69, CD45, TCR-alpha, and MHC class I, and
      decreased expression of Thy-1 and heat-stable Ag. In addition, we observed TCR
      induced expression of the bcl-2 gene, a well described inhibitor of programmed
      cell death. Finally, TCR engagement decreased expression of recombinase
      activating genes and terminal deoxynucleotidal transferase genes, as well as
      V(D)J recombinase activity. However, TCR engagement did not elicit demonstrable
      CD4/CD8 lineage commitment. These observations suggest that engagement of the TCR
      on these DP cell lines elicits multiple maturation events that are part of the
      positive selection developmental program, but not CD4/CD8 lineage commitment.
      Thus, these DP cell lines provide the opportunity to elucidate molecular
      mechanisms of maturation and CD4/CD8 lineage commitment in vitro.

PMID- 7730609
TI  - Replacement of N-glycosylation sites on the MHC class II E alpha chain. Effect on
      thymic selection and peripheral T cell activation.
AB  - MHC class II molecules play a central role in thymic selection of developing T
      cells, Ag presentation to immunocompetent CD4+ T cells, and T cell activation by
      superantigens. We have established transgenic A.CA mice expressing either the
      wild-type E alpha d molecule (E alpha/E beta), or an E alpha d molecule altered
      at an N-glycosylation site on the E alpha chain (residue 78, 78E alpha/E beta or
      residue 118, 118E alpha/E beta) to identify a possible role for carbohydrates in
      thymic selection and peripheral T cell activation. Striking differences were
      found among these transgenic mice. Although V beta 10+ T cells were selected
      positively in all three transgenic strains, positive selection of V beta 7+ T
      cells was impaired in 118E alpha/E beta transgenic mice. Spleen cells from both
      strains with mutant E alpha chains showed selective defects in presentation of
      peptides to particular T cell hybridomas. In contrast, neither mutation affected
      presentation of the superantigen Mycoplasma arthriditis mitogen. These results
      demonstrate that alterations in the glycosylation of class II E alpha chains
      might affect both central and peripheral T cell regulation.

PMID- 7730610
TI  - Transfection of TCR alpha-chains into suppressor and T helper cell hybridomas.
      Production of suppressor factors with predicted antigen specificity.
AB  - Conditioned medium from Ag-specific suppressor T cell hybridomas contains soluble
      factors (TsF) that modulate immune responses in an Ag-specific manner. We
      previously generated a series of TCR-alpha- and TCR-beta- expression variants
      from a 4-hydroxy-3-nitrophenyl acetyl (NP)-specific inducer suppressor T cell
      hybridoma and demonstrated that loss of TCR alpha-chain mRNA, but not TCR-beta
      chain mRNA, was accompanied by concomitant loss of suppressor bioactivity.
      Suppressor factor bioactivity was restored by expression of TCR alpha-chain cDNA,
      suggesting that the TCR alpha-chain plays a critical role in Ag-specific
      suppressor cell function. We have now transfected TCR alpha-chain from a Th cell
      clone specific for arsanylated peptides plus I-Ad into a TCR-alpha- derivative of
      an NP-specific inducer suppressor T cell hybridoma. The transfectants expressed a
      new hybrid TCR-alpha beta complex and produced soluble factors that suppressed
      azobenzenearsonate hapten (ABA) but not NP delayed-type hypersensitivity
      responses. These supernatants mediated suppression of the induction, but not the
      effector phase of the delayed-type hypersensitivity reaction. In reciprocal
      experiments we transfected a TCR alpha-chain from an NP-specific suppressor T
      cell hybridoma into a TCR-alpha- hybridoma derived from the ABA-specific Th cell
      hybridoma. The NP-specific TCR alpha-chain was expressed in the Th cell
      hybridoma, but the supernatant from this transfectant did not suppress DTH
      responses to either NP or ABA. However, the latter supernatants, when combined
      with cell lysates derived from a TCR-alpha- Ts hybridoma, specifically suppress
      NP DTH responses. These data are consistent with the interpretation that TCR
      alpha-chain imparts Ag specificity to the suppressor molecule and a second, yet
      undefined, component produced by the Ts hybridoma controls the immunoregulatory
      bioactivity.

PMID- 7730611
TI  - Met-enkephalin-containing peptides encoded by proenkephalin A mRNA expressed in
      activated murine thymocytes inhibit thymocyte proliferation.
AB  - Murine thymocytes activated with the mitogen Con A express proenkephalin A mRNA
      (PEA mRNA) and met-enkephalin and/or met-enkephalin-containing peptides
      ("enkephalins"). This Con A-induced expression of PEA mRNA is modulated by the
      delta opioid receptor agonist, deltorphin I, in a biphasic, dose-dependent
      manner. That is, 10(-13) M to 10(-11) M deltorphin enhanced PEA mRNA expression 3
      to 3.5-fold over the level induced by Con A alone, and 10(-9) M to 10(-7) M
      deltorphin inhibited it 40 to 70%. delta opioid receptor antagonists recognizing
      the delta-2 (naltrindole (NTI) and naltriben (NTB)), but not the delta-1 (7
      benzylidenenaltrexone (BNTX)), subtype of opioid receptor described in brain,
      reversed both the enhancing and inhibiting effects of deltorphin on Con A-induced
      PEA mRNA expression. In addition, the delta-2 receptor-specific antagonists, NTI
      and NTB, directly inhibited Con A-induced PEA mRNA expression. The function of
      the enkephalins expressed by thymocytes was examined by using 1) delta opioid
      receptor antagonists, 2) PEA mRNA-specific antisense cDNA, and 3) Ab to met
      enkephalin, and measuring cell proliferation. All three reagents caused
      enhancement of Con A-induced proliferation, with effects ranging from two- to
      fourfold over the response to Con A alone. Again, the delta-2 subtype-specific
      antagonists, NTI and NTB, were functional and the delta-1 subtype-specific
      antagonist, BNTX, was not. The PEA mRNA-specific antisense cDNA blocked
      translation but not transcription of PEA mRNA. The data suggest that 1)
      endogenous enkephalins induced in thymocytes modulate their own expression
      through delta-2-like opioid receptors, and 2) these endogenous enkephalins
      function to inhibit the proliferation of activated thymocytes.

PMID- 7730612
TI  - IL-9 induces expression of granzymes and high-affinity IgE receptor in murine T
      helper clones.
AB  - Interleukin 9 (IL-9) is a TH2 cytokine that has been shown to promote the antigen
      independent growth of some mouse T helper clones. To characterize the specificity
      of IL-9-mediated T cell activation, we used a murine T cell clone that could grow
      with either IL-9 or IL-2. After differential hybridization of a cDNA library, we
      isolated three genes that were expressed preferentially in the presence of IL-9.
      Two of them correspond respectively to granzyme A and granzyme B, two proteases
      expressed by activated T cells. By Northern blot hybridization and functional
      assays, we found that IL-9 induced the expression of granzyme B in several T cell
      clones as well as in mast cell lines. In addition, other proteases such as the
      mouse mast cell proteases were also found to be expressed by IL-9-activated T
      cell clones. The third IL-9-induced cDNA corresponds to the alpha-chain of the
      high-affinity receptor for IgE. Several T cell clones expressed this IgE receptor
      mRNA and were able to bind IgE with high affinity. Taken together, our results
      indicate that IL-9 induces a mast cell-like phenotype in T cell clones.

PMID- 7730613
TI  - Dendritic cells produce IL-12 and direct the development of Th1 cells from naive
      CD4+ T cells.
AB  - Dendritic cells are APCs that are unique in their potency to stimulate
      proliferation of primary Ag-specific responses in vitro and in vivo. In this
      study, we demonstrate that dendritic cells can produce IL-12, a dominant cytokine
      involved in the development of IFN-gamma-producing T cells. This finding resulted
      from our observations that dendritic cell-induced Th1 development from total CD4+
      T cells upon neutralization of endogenous levels of IL-4 was IL-12-dependent.
      Furthermore, we demonstrate that dendritic cells can induce the development of
      Th1 cells from Ag-specific naive LECAM-1bright CD4+ T cells obtained from alpha
      beta-TCR transgenic mice, provided that CD4+ LECAM-1dull T cells, which produce
      significant levels of IL-4, are not present in the primary cultures. Production
      of IL-12 by dendritic cells was confirmed by positive immunofluoresence staining
      with Abs specific for the inducible IL-12 p40 subunit. This suggests that in
      addition to inducing proliferation and clonal expansion of naive T cells,
      dendritic cells, by their production of IL-12, play a direct role in the
      development of IFN-gamma-producing cells that are important for cell-mediated
      immune responses.

PMID- 7730614
TI  - Adoptive cell transfer of contact sensitivity-initiation mediated by nonimmune
      cells sensitized with monoclonal IgE antibodies. Dependence on host skin mast
      cells.
AB  - A role for mast cell release of serotonin (5-HT), via Ag-specific factors derived
      from Thy-1+ B220+ lymphoid cells in the initiation of murine contact sensitivity
      (CS) has been suggested. However, because CS in mast cell-deficient mice was
      intact, a role for mast cells in CS initiation was unclear. Therefore, we
      examined whether CS could be initiated by i.v. injection of nonimmune mixed
      lymphoid cells that were sensitized in vitro with IgE. When naive mice received
      IgE-sensitized nonimmune spleen or lymph node cells, or IgE-sensitized purified
      mast cells, together with immune CS-effector B220- T cells, which therefore were
      depleted of CS-initiating, Thy-1+, B220+ cells, which could not transfer CS, then
      reconstitution of CS occurred. Mast cell-deficient W/Wv mice could not elicit
      this IgE-dependent CS ear swelling, but when mast cell deficiency was reversed by
      ear injection of normal bone marrow-derived cultured mast cells, then CS was
      restored. In vitro pretreatment with irrelevant monoclonal anti-OVA IgE prevented
      CS initiation mediated by Ag-specific, IgE mAb-sensitized cells, presumably by
      blocking sensitization with IgE. Thus Fc epsilon R on the normal lymphoid cells
      were involved. When ketanserin, a 5-HT2 receptor antagonist, was injected i.v.
      before cell transfer, CS initiation via IgE-sensitized cells and CS were no
      longer elicited. Thus, in this system, IgE Abs bound to circulating IgE Fc
      epsilon R bearing lymphoid cells sensitized in vitro (most likely basophils),
      probably mediated early activation of these circulating basophils to release
      mediators, causing 5-HT release from cutaneous mast cells, to mediate CS
      initiation.

PMID- 7730615
TI  - Synergistic effects of IL-7 and IL-12 on human T cell activation.
AB  - We have previously demonstrated that human rIL-12 alone can augment the
      development of cytotoxic activity in stimulated CD8+ T cells. The present study
      was undertaken to examine the interactions of rIL-7 and rIL-12 on human
      peripheral blood T cell activation and CTL differentiation. Purified T
      lymphocytes were pulsed overnight with immobilized alpha-CD3 and then cultured
      for 3 additional days with IL-7 and/or IL-12. The combination of IL-7 and IL-12
      synergistically enhanced the proliferation of either fresh CD3+ T cells or an IL
      2-dependent CD4+ T cell line, Kit-225-K6. This synergy was seen on both subsets
      of T cells; however, CD8+ T cells were usually more responsive to IL-7 and IL-12
      at lower concentrations than were CD4+ T cells. Furthermore, these cytokines
      additively/synergistically augmented the cytotoxic activity of CD8+ T cells. Abs
      to IL-2 and IL-2R alpha blocked the synergistic effect on proliferation of CD4+ T
      cells, but had a minimal effect on the synergistic response of the proliferative
      and cytotoxic activity of CD8+ T cells. Examination of the effects of IL-7 and IL
      12 on the expression of IL-12 receptor on T cells revealed an increase in the
      subunit of IL-12R by IL-7 as determined by flow cytometric analysis. We analyzed
      the effects on IFN-gamma production by CD8+ T cells and found that IL-7 alone did
      not induce detectable levels of IFN-gamma production but together with IL-12 it
      synergistically enhanced the production of IFN-gamma. We also found that IFN
      gamma was probably not required for enhanced CTL activity of CD8+ T cells,
      because Ab to human IFN-gamma did not block additive/synergistic effects of
      either cytokine. The synergistic stimulatory activity of IL-7 and IL-12 may be of
      significance in vivo and may provide an alternative mechanism of stimulating T
      cells for use in immunotherapy.

PMID- 7730616
TI  - Cell expansion and growth arrest phases during the transition from precursor (CD4
      8-) to immature (CD4+8+) thymocytes in normal and genetically modified mice.
AB  - T cell early precursors belong to the CD3-CD4-CD8- triple negative (TN) thymocyte
      population that can be subdivided on the basis of CD44, CD25, and heat-stable Ag
      (HSA) expression. The kinetics and precursor product relationships of these
      subsets, as well as of the CD4/8low intermediates, were studied by using pulse
      labeling with bromodeoxyuridine (BrdUrd). The highest frequencies of DNA
      synthesizing cells were found in CD44+CD25+ and CD44-CD25low or CD25- subsets.
      The major TN cell type (CD44-CD25high), as well as CD44+ CD25-HSAlow early
      precursors, contained a majority of resting cells. RAG-2-/- mice contained less
      cells in DNA synthesis than normal mice, and CD44-CD25-/low cells were absent. In
      female mice transgenic for the anti-HYTCR, CD44-CD25high cells were almost all
      cycling, but a high percentage of resting cells was found in CD44-CD25- cells. In
      days following the BrdUrd pulse, there was a reduction in the number of BrdUrd+
      cells in most subsets, with the exception of the labeled CD44-CD25high cells that
      showed a bell-shaped curve. The kinetics and cell size evolution suggest that the
      majority of these cells do not give rise to CD4+CD8+ cells. In RAG-2-/- cells,
      the block at the CD44-CD25high stage involved all cells. In TCR transgenic (Tg)
      mice, no block was seen at the CD44-CD25high stage, suggesting that early
      expression of a complete TCR receptor precludes the normal selection step.
      However, another block in the differentiation process was observed at the CD44
      CD25- step in TCR Tg mice, suggesting an additional selection point.

PMID- 7730617
TI  - Effect of IL-12 on immune suppression and suppressor cell induction by
      ultraviolet radiation.
AB  - The carcinogenic potential of UV radiation (the primary cause of nonmelanoma skin
      cancer) is associated with its ability to suppress cell-mediated immune
      responses. Previous studies have shown that this UV-induced immune suppression is
      caused by the secretion of immunosuppressive cytokines such as IL-10. Because the
      effects of IL-10 on the immune response are countered by IL-12, we injected
      irradiated mice with IL-12 to determine whether it could overcome UV-induced
      immune suppression. Administration of IL-12 blocked the suppression of delayed-in
      time hypersensitivity reactions observed in UV-irradiated animals. Moreover, IL
      12 prevented the induction of suppressor T cells, in that adoptive transfer of
      spleen cells from UV-irradiated mice treated with IL-12 had no effect on the
      immune response of the recipient mice, whereas transfer of spleen cells from UV
      irradiated mice treated with the vehicle inhibited the immune response. In
      addition, IL-12 neutralized the activity of UV-induced suppressor T cells.
      Although the adoptive transfer of UV-induced suppressor T cells from irradiated
      mice suppressed the immune response of the recipient mice, treatment of the
      recipient mice with IL-12 following the adoptive transfer overcame the immune
      suppression. The results of these experiments demonstrate that IL-12 can overcome
      UV-induced immune suppression by preventing the induction of, as well as
      neutralizing the activity of pre-formed suppressor T cells.

PMID- 7730618
TI  - Cellular distribution and costimulatory function of rat CD28. Regulated
      expression during thymocyte maturation and induction of cyclosporin A sensitivity
      of costimulated T cell responses by phorbol ester.
AB  - CD28 has been identified in man and mouse as a potent costimulatory receptor on T
      cells. We have generated a mAb, called JJ319, to rat CD28 and show that it is
      expressed on virtually all peripheral rat alpha beta and on most gamma delta T
      cells, and on about half of NK cells. In contrast to the mouse but as in humans,
      most immature CD4+8+TCRlow thymocytes express little or no CD28, whereas CD28
      expression is high on TCRintermediate and TCRhigh cells. mAb JJ319 very
      effectively costimulates T cell proliferation and IL-2 secretion by resting rat T
      cells. In contrast to results obtained in mice and humans, phorbol ester did not
      synergize in T cell activation with CD28-specific mAb but even induced
      sensitivity to cyclosporin A in T cell cultures that were optimally costimulated
      by mAbs to the TCR and to CD28. This result points to a novel effect of protein
      kinase activation by phorbol ester on signal transduction by TCR plus CD28
      costimulation which only becomes apparent if, as in the rat, the TCR-mediated
      signal cannot be replaced by phorbol ester.

PMID- 7730619
TI  - Colony-stimulating factor-1 secreted by fibroblasts promotes the growth of
      dendritic cell lines (XS series) derived from murine epidermis.
AB  - We have established recently from mouse epidermis long-term dendritic cell lines
      (XS series) that resemble epidermal Langerhans cells (LC) by their surface
      phenotype, Ag-presenting profile and cytokine mRNA profile. The growth of XS
      lines was promoted maximally by granulocyte-macrophage-CSF or by a factor
      secreted by NS lines, which are fibroblastic cell lines established from dispase
      separated specimens of mouse epidermis. The purpose of this study was to
      determine the identity of XS cell growth factor secreted by NS cells. We report
      the following: 1) NS cells express constitutively mRNA for CSF-1; 2) XS cells
      express the CSF-1R at mRNA and protein levels; 3) rCSF-1 mimics NS culture
      supernatant in its ability to promote XS cell growth; 4) NS supernatant-dependent
      XS cell growth is blocked completely by each of two Abs against the CSF-1R. We
      conclude that CSF-1 is responsible for the XS growth-promoting activity secreted
      by NS lines. We also report the following: 5) LC freshly isolated from skin
      express CSF-1R mRNA; and 6) fibroblasts derived from specimens of dermis also
      express mRNA and secrete large amounts (50-100 ng/ml) of CSF-1. These
      observations give rise to a new concept that dermal fibroblasts may support the
      survival and growth of LC (and their precursors) through the paracrine effect of
      elaborated CSF-1.

PMID- 7730620
TI  - Production of IL-5 by human NK cells and regulation of IL-5 secretion by IL-4, IL
      10, and IL-12.
AB  - Human NK cells produce IFN-gamma, TNF-alpha, and granulocyte macrophage-CSF when
      stimulated with susceptible target cells or through the CD16 and CD94 cell
      surface molecules. This study reports that NK cells also produce IL-5, a cytokine
      typically produced by Th2 cells, which mediates mobilization and differentiation
      of eosinophils. Polyclonal NK cell populations and NK cell clones produce IL-5
      when stimulated to proliferate with gamma-irradiated MM-170 melanoma cells or JY
      B-lymphoblastoid cells and rIL-2. IL-5 is produced in cultures generated from
      freshly isolated NK cells (primary cultures) and when quiescent NK cells from
      primary cultures are restimulated to proliferate (secondary cultures). Production
      of IL-5 is on average 8.8-fold greater in secondary cultures compared with
      primary cultures (n > 18), suggesting that the ability of NK cells to produce IL
      5 matures during primary stimulation. IL-5 secretion, particularly in primary
      cultures, is augmented by IL-4 and is inhibited by IL-12 and IL-10. By contrast,
      IL-4 and IL-12 have the reverse effects on IFN-gamma secretion. Cultured NK cells
      that no longer secrete cytokines can be restimulated to do so with either phorbol
      12, 13 dibutyrate and ionomycin or with susceptible target cells in the presence
      of rIL-2. IL-5 production in these cultures occurs only when NK cells are in an
      exponential growth phase, whereas IFN-gamma, TNF-alpha, and granulocyte
      macrophage-CSF are produced also by stimulation of quiescent cells, although to a
      lesser extent. Furthermore, cytokine production is unrelated to the cytolytic
      activity of NK cells. In conclusion, proliferating human NK cells have the
      potential to produce IL-5 with secretion regulated by IL-4, IL-10, and IL-12.

PMID- 7730621
TI  - Requirement for peptide in alloreactive CD4+ T cell recognition of class II MHC
      molecules.
AB  - To examine the role of peptide in alloreactive class II MHC-restricted responses,
      we transfected I-A molecules into the Ag-processing defective mutant cell line,
      T2. Consistent with their defective Ag-processing phenotype, the T2 transfectants
      predominantly express SDS-unstable I-A molecules on their surface. These cells
      and phenotypically normal APCs were used to study primary and secondary
      alloreactive T cell responses in limiting dilution assays. The results
      demonstrate that the majority of CD4 T cells that participate in primary
      alloresponses and essentially all the CD4 T cells that participate in secondary
      alloresponses recognize I-A conformers that depend on the presence of peptide and
      do not recognize the SDS-unstable I-A expressed by T2 transfectants. To further
      investigate the requirement for peptide in these responses, we incubated the T2
      transfectants with E alpha 52-68 peptide and generated SDS-stable I-A-peptide
      complexes on the cell surface. The I-Ab-E alpha peptide complexes expressed on T2
      cells are stimulatory in secondary alloresponses if the T cells were exposed to
      the same I-A peptide complex during the priming step. These studies demonstrate
      that peptide-containing class II MHC is the relevant ligand for alloreactive T
      cells, and identify an alloreactive response to a peptide (E alpha 52-68) derived
      from a highly expressed cell surface "self" Ag, the I-E molecule.

PMID- 7730622
TI  - T cell development in TCR-alpha beta transgenic mice. Analysis using V(D)J
      recombination substrates.
AB  - The major pathway of intrathymic T cell differentiation leads CD4-8- (DN) T
      lineage-committed precursors to TCR-alpha beta+ CD4+8- or CD4-84+ (SP) T
      lymphocytes. The expression of functionally rearranged TCR-alpha beta transgenes
      (Tg-TCR) may influence thymocyte development by affecting the various selection
      events that control T cell differentiation. To gain insights into these
      processes, we have produced double transgenic animals carrying V(D)J
      recombination substrates in addition to the MHC class I (H-2Kb) allospecific
      KB5C20 Tg-TCR. We have analyzed substrate rearrangements in purified populations
      of Tg-TCR+ thymocytes in the situation of positive or negative selection. The
      profile of rearrangements found in SP thymocytes, positively selected for the Tg
      TCR, suggests that expression of the KB5C20 Tg-TCR has only a minimal influence
      on substrate V(D)J recombination in cells differentiating along the major alpha
      beta T cell developmental pathway. In contrast, Tg-TCR+ DN thymocytes, in both
      positively and negatively selecting haplotypes, presented a profile that implies
      premature cessation of substrate rearrangements. This profile was maintained in
      peripheral Tg-TCR+ DN cells and was distinct from the one found in CD25+, alpha
      beta+, or gamma delta+ DN cells purified from mice transgenic for the
      recombination substrates only. These results are discussed with respect to the
      possible origin and differentiation pathway of Tg-TCR+ DN and SP cells.

PMID- 7730623
TI  - Aglycosylated and phosphatidylinositol-anchored MHC class I molecules are
      associated with calnexin. Evidence implicating the class I-connecting peptide
      segment in calnexin association.
AB  - The endoplasmic reticulum resident protein calnexin interacts with several
      glycoproteins including class I MHC molecules. Calnexin is thought to retain free
      class I heavy chains and/or promote their folding and assembly with beta 2
      microglobulin and peptide ligand. Whereas with other glycoproteins, Asn-linked
      glycans seem to be involved in calnexin association, with class I molecules the
      transmembrane region has been implicated. To critically define the structures on
      class I molecules that determine their interaction with calnexin, we have studied
      carbohydrate-deficient and transmembrane-variant class I molecules. Carbohydrate
      deficient class I molecules were found to accumulate intracellularly in an open,
      non-beta 2-microglobulin-associated conformation. However, open as well as
      conformed class I molecules showed significant calnexin association whether they
      were aglycosylated or fully glycosylated. Thus, carbohydrate moieties may be
      necessary for efficient class I folding, but are not required for calnexin
      association. Calnexin was also found associated with a soluble class I molecule
      that has a truncated transmembrane segment, demonstrating that membrane
      attachment of class I is not required for interaction with calnexin. Finally, two
      isoforms of the class Ib molecule Q7b were compared. Unexpectedly, the
      glycosylphosphatidylinositol-anchored Q7b isoform was found associated with
      calnexin, whereas the soluble Q7b isoform was not calnexin associated. These
      comparisons of Q7b isoforms implicate the class I-connecting peptide segment and
      not the transmembrane region as a site of interaction with calnexin.

PMID- 7730624
TI  - Activation of transcription by binding of NF-E1 (YY1) to a newly identified
      element in the first exon of the human DR alpha gene.
AB  - A previously unrecognized element, located downstream of the start site of
      transcription in the first exon of the DR alpha gene, has been defined that
      enhances promoter activity up to eightfold in a position-dependent manner.
      Mutations in this DNA-binding site abolished binding of a nuclear factor in human
      B cell nuclear extract and decreased the activity of the DR alpha promoter to a
      basal level. Significant sequence homology of this element was found in the DNA
      of the DR beta, DP alpha and -beta, and DQ alpha genes, always located downstream
      of the transcriptional start site. The nuclear factor binds to the DR alpha and
      DP alpha element but not to the element in the DQ alpha gene. It was identified
      as NF-E1 (YY1). This protein, previously identified by its binding to the Ig
      kappa 3' enhancer and the Ig heavy chain mu E1 site, thus also appears to be
      quite important in the regulation of MHC class II gene expression.

PMID- 7730625
TI  - Structure of the human C7 gene and comparison with the C6, C8A, C8B, and C9
      genes.
AB  - The seventh component of complement is a single chain plasma glycoprotein that is
      involved in the cytolytic phase of complement activation. We have determined the
      structure of the C7 gene, which is encoded by 18 exons whose sizes vary from 56
      to 244 bp. For the most part, the exons do not correspond to the protein homology
      units. However, two intron/exon boundaries occur at junctions between different
      functional parts of the protein. The first is at a site between the end of the C9
      homology unit and the carboxyl-terminal extension which is also a feature of C6.
      The second of these boundaries occurs between the regions encoding two pairs of
      cysteine-rich modules (the short consensus repeats and the factor I modules)
      located in the carboxyl-terminal part of C7. In contrast to the exons, the
      introns range considerably in size from 0.5 to 8.5 kbp. The complete analysis
      indicates that the gene encoding C7 is approximately 80 kbp in length. We show
      here that the C7 gene is highly homologous to that for C6, and also to C8A, C8B,
      and C9, confirming and extending the published data. With the exception of exon
      1, all intron/exon boundaries are preserved with respect to phase when compared
      with C6.

PMID- 7730626
TI  - The role of c-Myb or a related factor in regulating the T cell receptor gamma
      gene enhancer.
AB  - An enhancer has been localized 3 kb downstream of the C gamma 1 gene segment of
      the murine TCR-gamma locus. One element, the gamma 3 site, has been shown to be
      critical for its functional activity. Here we have determined that Myb-related
      transcription factors bind to the gamma 3 site and appear to be critical for the
      full activity of the TCR-gamma enhancer. c-myb products can transactivate the
      gamma 3 site in cell lines that do not ordinarily support enhancer activity of
      the gamma 3 site. Mutations in the myb site or an adjacent site for core-binding
      factor(s) prevent transactivation. c-myb expression in various cell lines is
      consistent with their capacity to activate the gamma 3 enhancer element using
      transient transfection assays. Therefore, c-Myb or a related factor appears to
      play an important role in regulating the murine TCR-gamma enhancer.

PMID- 7730627
TI  - DNA sequencing of the gene encoding a bacterial superantigen, Yersinia
      pseudotuberculosis-derived mitogen (YPM), and characterization of the gene
      product, cloned YPM.
AB  - Previously, we found a novel bacterial superantigen from Yersinia
      pseudotuberculosis, designated Y. pseudotuberculosis-derived mitogen (YPM). In
      the present study, we analyzed the DNA sequence of the gene encoding YPM. The YPM
      gene was cloned into a plasmid vector pMW119 and expressed in Escherichia coli
      DH10B. Like the native YPM, the cloned YPM required the expression of MHC class
      II molecules on accessory cells in the induction of IL-2 production by human T
      cells. TCR-V beta repertoire of human T cells reactive with the cloned YPM was V
      beta 3, V beta 9, V beta 13.1, and V beta 13.2. This repertoire is the same as
      that of T cells reactive with the native YPM. These results indicate that the
      cloned YPM expressed in E. coli is identical to the native YPM. Sequencing of the
      YPM gene revealed that the gene contained an open reading frame of 456 base pairs
      encoding a precursor form of 151 amino acid residues with m.w. 16,679 that is
      processed into a mature form of 131 amino acid residues with m.w. 14,529.
      Homology analysis revealed that the homology of amino acid sequence is quite low
      among YPM and other well known bacterial superantigens. We designated the gene
      encoding YPM as ypm.

PMID- 7730628
TI  - The interferon-stimulated response element and a kappa B site mediate synergistic
      induction of murine IP-10 gene transcription by IFN-gamma and TNF-alpha.
AB  - The present study investigates mechanisms involved in cooperation between IFN
      gamma and TNF-alpha to promote transcription from the IP-10 gene in NIH 3T3
      cells. IFN-gamma synergistically enhanced TNF-alpha-induced levels of IP-10 mRNA,
      whereas levels of JE (MCP-1) or KC (GRO/MGSA) mRNA induced by TNF-alpha were
      unaffected by IFN-gamma. The cooperation between IFN-gamma and TNF-alpha for
      induction of IP-10 mRNA was independent of de novo protein synthesis and mediated
      at least in part by increased transcription. Transient transfection analysis with
      a 243-bp fragment flanking the transcription start site of the murine IP-10 gene
      indicated that synergy between the two stimuli was dependent upon occupancy of at
      least two of three critical regulatory sequence elements: an IFN-stimulated
      response element (ISRE) and one of two kappa B sites. IFN-gamma and TNF-alpha
      independently activated nuclear factors capable of specific interaction with the
      ISRE and kappa B sites, respectively. IFN-gamma induced two ISRE binding
      complexes, one of which was protein synthesis independent, appeared within 15 min
      of stimulation, and contained p91 or signal transducer and activator of
      transcription (STAT) 1. TNF-alpha induced only one ISRE binding activity, which
      was dependent upon protein synthesis. TNF-alpha also induced kappa B binding
      activity that was composed of NF-kappa B1 (p50) and RelA (p65) whereas IFN-gamma
      had no detectable effect on kappa B binding activity. Together these results
      indicate that the highly synergistic transcriptional activation of the IP-10 gene
      by IFN-gamma and TNF-alpha involves the cooperation between factors that are
      independently activated by the two stimuli and that bind to independent sites.

PMID- 7730629
TI  - Cyclic AMP inhibits expression of the IL-2 gene through the nuclear factor of
      activated T cells (NF-AT) site, and transfection of NF-AT cDNAs abrogates the
      sensitivity of EL-4 cells to cyclic AMP.
AB  - cAMP inhibits PMA-induced IL-2 production at the transcriptional level in EL-4, a
      mouse lymphoma line. The region of the mouse IL-2 promoter covering positions
      from -321 to +46 relative to the transcription initiation site is required for
      activation by PMA and inhibition by cAMP. This region contains the nuclear factor
      of activated T cells (NF-AT), nuclear factor-kappa B (NF-kappa B), AP-1, and Oct
      binding sites, and the role of each element in responding to PMA and/or cAMP
      signals was characterized. The IL-2 promoter carrying mutations in each element
      reduced response to PMA while it retained sensitivity to cAMP, thereby suggesting
      that multiple elements contribute to positive and negative responses to PMA and
      cAMP, respectively. Using reporter plasmid carrying multiple copies of each
      element, we then found that the NF-AT construct was most effective in responding
      to PMA activation and to cAMP inhibition. Electrophoretic mobility shift assay
      revealed that, after exposure of cells to Bt2cAMP, NF-AT binding complex changed
      in amount or in mobility as a function of time. Furthermore, overexpression of
      the cytoplasmic component of NF-AT abrogated the inhibitory action of cAMP. These
      results indicate that the NF-AT site is a target of the inhibitory action of
      cAMP. In addition, binding of the NF-kappa B (p50/p65) heterodimer to the NF
      kappa B site was inhibited by cAMP. Taken together, our data show that cAMP in EL
      4 cells inhibits mouse IL-2 gene transcription through cis regulatory elements
      that include the NF-AT site as well as the NF-kappa B site.

PMID- 7730630
TI  - Assembly of IgM. Role of disulfide bonding and noncovalent interactions.
AB  - Polymeric IgM is usually envisaged as an array of mu 2L2 monomers in which the mu
      heavy chains are held together by disulfide bonds involving cysteines at
      positions 337, 414, and 575. We have studied the importance of inter-mu-chain
      disulfide bonds for formation of IgM polymers and monomers by analyzing the
      effects of eliminating one or more of these disulfide bondings. Ablation of all
      inter-chain bonds by either chemical reduction and alkylation or by mutagenesis
      resulted in the exclusive production of halfmers (muL) molecules. IgM composed of
      mu-chains bearing each of the other six possible combinations of cysteine to
      serine replacements was produced as different mixtures of polymers, monomers, and
      halfmers. Cysteine 575 was both necessary and sufficient for efficient assembly
      of IgM polymers and sufficient but not necessary for efficient assembly of
      monomers. Cysteine 337 was sufficient but not necessary for efficient assembly of
      monomers, and was neither sufficient nor necessary for formation of polymers.
      Cysteine 414 was neither necessary nor sufficient for efficient formation of
      either monomers or polymers. Data also suggest that noncovalent interactions
      between C mu 2 domains are stronger than the interactions between C mu 4/tail
      domains.

PMID- 7730631
TI  - Growth inhibition of Candida albicans hyphae by CD8+ lymphocytes.
AB  - We have shown previously that IL-2-activated splenocytes can inhibit the growth
      of Candida albicans hyphae in vitro. Herein we demonstrate that plastic
      nonadherent lymphocytes that are CD8+ mediate the antifungal activity. Enrichment
      for CD8+ cells markedly enhanced the antifungal activity of the IL-2-activated
      lymphocyte population for C. albicans and the cytotoxic activity of the
      lymphocytes for an NK-resistant cell line. Depletion of CD8+ cells reduced the
      lymphocyte population's antifungal activity and cytotoxic activity for the NK
      resistant cell line. Enrichment for NK1.1+ cells markedly reduced the antifungal
      activity of the lymphocyte population for C. albicans and increased the cytotoxic
      activity of the lymphocytes for an NK-sensitive cell line. Depletion of NK1.1+
      cells increased the lymphocyte population's antifungal activity and cytotoxic
      activity for the NK-resistant cell line. Generation of the antifungal lymphocytes
      in culture required IL-2 and was not replaced with IFN-gamma. These data show
      that IL-2-activated CD8+ T lymphocytes exert the greatest amount of antifungal
      effect against the hyphal form of C. albicans, whereas IL-2- or IFN-gamma
      activated NK cells have little or no effect against the hyphae.

PMID- 7730633
TI  - 5-Fluorocytosine-induced eradication of murine adenocarcinomas engineered to
      express the cytosine deaminase suicide gene requires host immune competence and
      leaves an efficient memory.
AB  - The nonmammalian cytosine deaminase (CD) enzyme converts the nontoxic prodrug 5
      fluorocytosine (5-FC) to the toxic metabolite 5-fluorouracil. Parental cells of a
      mammary adenocarcinoma (TSA-pc) of BALB/c mice were transfected with the CD gene
      (TSA-CD), and the ability of 5-FC to hamper their growth was evaluated. A
      quantity amounting to 0.5 mg of 5-FC/0.3 ml of medium inhibits the proliferation
      of TSA-CD cells, but not that of TSA-pc, nor that of TSA-pc transfected with
      neomycin-resistance gene only (TSA-neo). In BALB/c mice, 800 mg 5-FC/kg of body
      weight injected daily i.p. for 30 days causes total regression of incipient (1
      day-old), and established (3- and 7-day-old) TSA-CD tumors, and of 3-day-old
      experimental lung metastases, but does not impair TSA-pc nor TSA-neo cell growth.
      Because in CD8+ T lymphocyte- and granulocyte-depleted mice 5-FC no longer
      impairs TSA-CD growth, immune mechanisms appear to play an important role in this
      regression. Following, regression, all mice are resistant to subsequent s.c. or
      i.v. lethal challenges with TSA-pc. The induction of this immune memory is
      dependent on CD4+ lymphocytes, whereas its effector phase depends on both CD4+
      and CD8+ lymphocytes. The memory elicited in tumor-bearing mice by the 5-FC
      dependent regression of TSA-CD tumors cures a significant number of mice with 4
      day-old TSA-pc metastases, but does not impair the growth of 4-day-old solid s.c.
      tumors. The reliability of this regression and the subsequent establishment of an
      efficient immune memory against poorly immunogenic TSA-pc offer the prospect that
      CD-transduced tumor cells and 5-FC can be used as components of a live antitumor
      vaccine.

PMID- 7730632
TI  - IL-2 enhances the function of recombinant poxvirus-based vaccines in the
      treatment of established pulmonary metastases.
AB  - Neoplastic cells are generally poor immunogens. Transfection of the murine tumor
      CT-26 with beta-galactosidase (beta-gal), a protein from Escherichia coli, did
      not alter its growth rate in vivo, or its lethality, and did not elicit a
      measurable anti-beta-gal immune response. Immunization with beta-gal-expressing
      recombinant vaccinia viruses (rVV) elicited specific anti-beta-gal cytolytic T
      lymphocytes, but rVV-beta-gal was only marginally therapeutic when given to tumor
      bearing mice. With the aim of expanding the immune response against beta-gal,
      used here as a model tumor Ag, we gave mice exogenous IL-2 starting 12 h after
      the poxvirus. The therapeutic effectiveness of the combination of poxvirus and IL
      2 was far greater than either of these treatments alone. When the cDNA for IL-2
      was inserted into the viral genome of the rVV construct to make a double
      recombinant (drVV), antitumor activity was further augmented. One mechanism of
      action may be the enhanced activation or expansion of cytotoxic T cells, because
      a marked increase in primary cytotoxic responses against vaccinia determinants
      was observed. Interestingly, other cytokines (mGM-CSF, mTNF-alpha, and mIFN
      gamma) inserted into the rVV genome did not modify the efficacy of the rVV
      constructs. The increase in specific CTL responses against beta-gal by drVV
      expressing the tumor-associated Ags (TAA) and IL-2 was more pronounced in mice
      bearing the lacZ-transduced tumor than in those bearing the parental cell line,
      suggesting that the TAA presented by growing tumor cells can either pre-activate
      or otherwise amplify the immune response induced by the rVV. Unfortunately, in
      several long-term surviving mice, tumor recurred that no longer expressed beta
      gal. These results indicate that treatment of disseminated tumors by using
      recombinant viruses expressing TAA can be enhanced by IL-2 provided exogenously,
      or encoded within the recombinant virus.

PMID- 7730634
TI  - Stimulation of TCR V gamma 3 cells by gram-negative bacteria.
AB  - A distinct feature of most murine TCR-gamma delta cells is that they localize in
      epithelial tissues that cover the internal and external surface of the body.
      Therefore, TCR-gamma delta cells have been hypothesized to represent a first line
      of defense against invading pathogens. In this study, it is shown that TCR V
      gamma 3 cells are activated to produce cytokines upon interaction with Gram
      negative bacteria, whereas Gram-positive bacteria have no effect. Accessory cells
      are not required. LPS of Gram-negative bacteria is shown to be the stimulating
      structure for TCR V gamma 3 cells, as the stimulation is inhibited by addition of
      polymyxin B or anti-LPS Ab and as purified LPS stimulates V gamma 3 T cells.
      Blocking of the V gamma 3 TCR does not inhibit stimulation by Gram-negative
      bacteria, whereas suboptimal triggering of the TCR is synergistic. These results
      demonstrate that LPS is an important stimulus for TCR V gamma 3 cells. This
      indicates that skin-located V gamma 3 T cells might play a role in the defense
      against Gram-negative bacteria.

PMID- 7730635
TI  - IL-12 is required for natural killer cell activation and subsequent T helper 1
      cell development in experimental leishmaniasis.
AB  - Infection of mice with the protozoan Leishmania major is an established in vivo
      model for the definition of factors that contribute to CD4+ T helper cell subset
      development. In the current study, a central role for IL-12 in directing both the
      innate and adaptive immune responses to L. major is established. We show that in
      vivo neutralization of IL-12 eliminates the NK cell cytotoxic response and IFN
      gamma production by lymph node cells from 2-day L. major-infected C3H mice.
      Moreover, anti-IL-12 treatment abrogated Th1 cell development and enhanced Th2
      cell development. Consistent with these results, elevated IL-12 p40 production
      and an increase in the number of IL-12 p40-producing cells were observed within 1
      day of infection in C3H mice. Because BALB/c mice lack an early NK cell response
      or a Th1-type immune response after L. major infection, we investigated the
      possibility that they had a defect in the ability to produce IL-12. Surprisingly,
      L. major infection stimulated IL-12 p40 production in BALB/c mice early after
      infection. Further studies suggest that BALB/c mice are unable to generate an
      early IFN-gamma response because of the simultaneous production of IL-12 and
      cytokines that inhibit IL-12 function, such as TGF-beta, IL-4, and IL-10.
      Together, these data show that IL-12 regulates the immune response to L. major,
      but that even when IL-12 is induced, Th1 cell development may be interrupted by
      simultaneous production of inhibitory cytokines.

PMID- 7730636
TI  - Increased opsonization of a prtH-defective mutant of Porphyromonas gingivalis W83
      is caused by reduced degradation of complement-derived opsonins.
AB  - Periodontitis is a disease of the supporting structures of the teeth that is
      caused by bacteria whose common ecologic niche is the gingival crevice or the
      periodontal pocket. Tissue destruction occurs in spite of both local and systemic
      immune responses against such bacteria. Porphyromonas gingivalis is considered to
      be an important pathogen in some forms of human periodontitis and is particularly
      interesting because of its multiplicity of virulence factors. We have previously
      observed that phagocytosis-resistant invasive strains of P. gingivalis
      proteolytically degrade C3 and IgG and accumulate less C3-derived opsonins during
      complement activation. We recently have cloned the prtH gene from P. gingivalis
      W83 that encodes a 97-kDa active protease, which has the capacity to degrade
      purified C3 protein. By using this cloned gene we created an allelic exchange
      mutant of P. gingivalis W83, designated V2296, in which the prtH gene was
      inactivated. This mutant was previously shown to be less virulent than its parent
      strain W83 in a mouse model of bacterial invasiveness. In the present study we
      have assessed the relative capacity of V2296 and W83 to be opsonized by
      complement and to be taken up by PMNs. The data demonstrate that V2296, in
      comparison with its parent strain W83, is less able to degrade C3 and that it
      accumulates significantly greater numbers of molecules of C3-derived opsonins on
      the bacterial surface in the form of C3b and iC3b during complement activation.
      Furthermore, opsonized V2296 is taken up in much higher numbers by human PMNs
      than W83, suggesting that the prtH gene product may be important in evasion of
      host defense mechanisms.

PMID- 7730637
TI  - Comparison of the binding of C3S and C3F to complement receptors types 1, 2, and
      3.
AB  - The two common polymorphic variants of C3 are C3S/HAV4.1- and C3F/HAV4.1+. It was
      reported previously that erythrocytes coated with C3F rosetted more strongly with
      mononuclear cells than erythrocytes coated with C3S. We examined the binding of
      C3S/HAV4.1- and C3F/HAV4.1+ to complement receptors CR1, CR2, and CR3. The
      binding of 125I-labeled C3b dimers to erythrocyte CR1 was measured. Scatchard
      analysis showed a two-binding constant model with very similar binding constants
      for dimers prepared with C3S and C3F: for C3S Kd1 = 18.3 +/- 2 nM; Kd2 = 6.2 +/-
      1 nM; for C3F Kd1 = 21.5 +/- 4 nM; Kd2 = 7.2 +/- 3 nM (mean +/- SEM). One-third
      of the binding sites were of the higher affinity. The rosetting of erythrocytes
      with different densities of iC3b, prepared from C3S or C3F, to CR2 on Raji cells
      was analyzed. The percentage of Raji cells rosetted was related to the coating
      dose of EC3bi: 400 molecules/cell = 9% rosettes; 5000 molecules/cell = 75%. The
      dose-response curves were very similar for C3S- and C3F-coated erythrocytes. CR3
      dependent rosetting was studied in a similar manner by using neutrophils
      activated with f-met-leu-phe. CR3-dependent rosette formation with the indicator
      erythrocytes (600 to 6000 iC3b/cell) increased from 10% to 60% in a dose
      dependent manner and was closely similar for C3S and C3F. Inhibition of CR2 and
      CR3 rosetting by fluid phase ligand was also studied. iC3b dimers (0.4 to 50
      micrograms/ml) inhibited CR2-dependent rosetting in a dose-dependent manner but
      had no inhibitory effect on CR3-dependent rosetting. When the dimers were
      absorbed to fluorescent microspheres, they mediated phagocytic uptake of the
      microspheres in a CR3-dependent manner by neutrophils. CR3-dependent binding by
      activated neutrophils required surface-bound ligand.

PMID- 7730638
TI  - Biologic activities of the beta-chemokine TCA3 on neutrophils and macrophages.
AB  - Previous in vivo and in vitro studies demonstrated that the murine beta-chemokine
      TCA3 is a chemoattractant for monocytes/macrophages and neutrophils. The ability
      of TCA3 to activate these cell populations is now evaluated. Treatment with 10 to
      20 nM rTCA3 induced a respiratory burst with the production of superoxide and
      hydrogen peroxide in both casein-elicited and unstimulated neutrophil and
      macrophage populations. In addition, TCA3 treatment induced the production of
      reactive nitrogen intermediates, whereas stimulation with higher concentrations
      (100 nM) of TCA3 induced the exocytosis of lysozyme and elastase in the presence
      of cytochalasin B (7 micrograms/ml). Subnanomolar concentrations (100 pM) of TCA3
      also caused integrin-mediated increases of adhesiveness to fibrinogen by
      neutrophils and macrophages. Increased adhesiveness is the most sensitive assay
      for TCA3 bioactivity. TCA3 treatment appears to involve signaling through a G
      protein-linked receptor as Pertussis toxin abolished the TCA3-mediated increase
      of adhesiveness and the production of reactive nitrogen intermediates. The dose
      dependence of the TCA3-mediated activities indicate a coordinated inflammatory
      response mediated by varying concentrations of TCA3.

PMID- 7730639
TI  - Tenidap-modulated proinflammatory cytokine activation of a monocyte cell line.
AB  - Dysregulated cytokine production, in particular of the monokines IL-1, IL-6, and
      TNF, has been implicated in the inflammatory response in rheumatoid arthritis and
      in promoting the ensuing tissue destruction. The 3-substituted 2-oxindole tenidap
      has proven anti-inflammatory actions both in vivo and in vitro, among which is
      the inhibition of TNF and IL-1 production by monocytes following activation by
      LPS. We have investigated this ability to modulate cytokine activity by studying
      its effects on cytokine-monocyte interactions and in particular IL-6 production,
      with the THP-1 monocyte cell line. Tenidap inhibited IL-6 production in a dose
      dependent manner when cells were stimulated with a combination of TNF-alpha and
      IFN-gamma. It also inhibited the priming effect of IFN-gamma, preventing the
      super-induction of IL-6 production following subsequent stimulation with TNF
      alpha and IFN-gamma. These effects occurred under conditions in which the cells
      were not irreversibly altered with respect to their protein synthetic activity.
      IFN-gamma-induced up-regulation of HLA-DR was also inhibited by tenidap. Tenidap
      appears to affect some aspect of the IFN-gamma activation pathway, possibly the
      differentiation of these immature monocytes to a more mature phenotype. The data
      presented here indicate that tenidap has the potential to modulate the cytokine
      network in chronic disease.

PMID- 7730640
TI  - Activation of the mitogen-activated protein kinase/cytosolic phospholipase A2
      pathway in a rat mast cell line. Indications of different pathways for release of
      arachidonic acid and secretory granules.
AB  - The role of mitogen-activated protein (MAP) kinase in the release of arachidonic
      acid was examined in a mutated mast cell (RBL-2H3(m1)) line that expressed both
      native Fc epsilon R1 and the G protein-coupled muscarinic m1 receptor.
      Stimulation of these cells with Ag, carbachol, Ca(2+)-ionophore, or thapsigargin
      resulted in the phosphorylation of Raf1, MEK1, p42mapk MAP kinase, and the
      recently cloned cytosolic phospholipase A2 (PLA2) and increased activities of
      both MAP kinase and PLA2, as well as release of arachidonic acid. Because this
      cascade of reactions was inhibited by guanosine 5'-(2-thiodiphosphate), it
      appeared to be dependent on a GTP-binding protein(s). These reactions, however,
      were not dependent on protein kinase C; the cascade was totally resistant to the
      actions of a selective protein kinase C inhibitor, Ro31-7549, whereas release of
      the secretory granule marker, hexosaminidase, was blocked by this agent.
      Differences between the stimulatory pathways for release of arachidonic acid and
      hexosaminidase were evident also from the effects of the kinase inhibitor,
      quercetin. The above cascade of reactions, including release of arachidonic acid,
      was inhibited by 50% with approximately 5 microM quercetin, whereas secretion was
      inhibited only at higher concentrations of inhibitor. Moreover, inhibition of the
      activation of MAP kinase and release of arachidonic acid were closely correlated.
      This and previous findings suggested that release of arachidonic acid was
      attributable to the regulation of cytosolic PLA2 by MAP kinase (for activation of
      PLA2) and Ca2+ (for association of PLA2 with the membrane), whereas release of
      hexosaminidase was regulated primarily by Ca2+ and protein kinase C.

PMID- 7730641
TI  - Antibacterial proteins of granulocytes differ in interaction with endotoxin.
      Comparison of bactericidal/permeability-increasing protein, p15s, and defensins.
AB  - Bactericidal/permeability-increasing protein (BPI), antibacterial 15-kDa protein
      isoforms (p15s), and defensins (neutrophil peptides or NPs) are granule
      associated antibacterial proteins of polymorphonuclear leukocytes (PMN) that have
      both direct and synergistic growth inhibitory activity against Gram-negative
      bacteria. In this study, we have compared in vitro the abilities of these
      antibacterial proteins, alone and in combination, to inhibit the endotoxic
      activity of isolated LPS and whole bacteria. All three proteins blocked endotoxin
      activity in: 1) the Limulus amoebocyte lysate assay, 2) priming of PMN for
      enhanced arachidonate release, and 3) stimulating leukocyte oxidase activity in
      1% blood. However, the proteins differ markedly in both relative potency (BPI >>
      p15s = NP1) in the presence of the plasma LPS-binding protein and in the range of
      LPS chemotypes that can be inhibited. BPI potently neutralizes LPS of any
      chemotype, but p15s and defensins are less active against long-chain (S-type)
      LPS. In whole blood ex vivo, the p15s and NP1 are approximately 1000-fold less
      potent than BPI, but at subinhibitory doses act in synergy with BPI to inhibit
      the TNF-inducing activity of a serum-resistant encapsulated strain of Escherichia
      coli (K1/r). The anti-endotoxic effects of p15 and NP1 against E. coli K1/r in
      whole blood appear secondary to growth arrest, because, in marked contrast to
      BPI, they are not evident against nonviable bacteria (pretreated with antibiotic)
      nor isolated LPS. Thus, BPI stands out for its ability to inhibit isolated or
      bacterial LPS under physiologic conditions. However, p15s and defensins may also
      contribute to suppression of endotoxic signaling by Gram-negative bacteria via
      synergistic (with BPI) growth inhibition upon extracellular release of these
      proteins from PMN during inflammation.

PMID- 7730642
TI  - TNF-alpha mediates recruitment of neutrophils and eosinophils during airway
      inflammation.
AB  - Airway inflammation is characterized by leukocyte extravasation around the
      peribronchial mucosa and into the airway of the lung. In the present study we
      utilized a model of airway inflammation induced by intratracheal challenge with
      soluble parasite (Schistosoma mansoni) egg Ag (SEA) in presensitized mice. The
      subsequent inflammatory response and leukocyte recruitment consists of early
      neutrophil (8 to 24 h) and later eosinophil (48 to 72 h) infiltration into the
      interstitium and airway. Little neutrophil and no eosinophil recruitment was
      observed in presensitized control mice challenged with vehicle. Multiple studies
      have demonstrated a crucial role for TNF-alpha during inflammatory responses. In
      these experiments we investigated the role of TNF-alpha in Ag-specific
      eosinophilic airway inflammation. Measurement of TNF-alpha expression by reverse
      transcriptase-PCR and ELISA in whole lung homogenates of SEA-challenged mice
      demonstrated an early increase in TNF-alpha levels (1 to 8 h). To determine the
      specific role of TNF-alpha in leukocyte recruitment during airway inflammation,
      mice were treated with soluble TNF-alpha receptor linked to an Fc Ab molecule
      (sTNFr-:Fc). This treatment has previously been used to effectively neutralize
      TNF in vivo. Intratracheal SEA-challenged mice treated with sTNFr-FC demonstrated
      significantly decreased leukocyte recruitment into the lung and airway. The
      inflammatory response in the lungs in sTNFr-Fc-treated mice was significantly
      decreased throughout the study period, as compared with control mice. An
      approximate decrease in early neutrophil infiltration into the airway was
      observed when sTNFr-Fc was administered 2 h before the Ag challenge. Eosinophil
      infiltration was also diminished when sTNFr-Fc was administered before Ag
      challenge. Interestingly, when sTNFr-Fc was administered therapeutically 24 h
      after Ag challenge, the eosinophil response was nearly abrogated at 48 h after
      challenge. These studies indicate that TNF-alpha acts as an initial inflammatory
      cytokine that subsequently regulates both early neutrophil infiltration and
      eosinophil recruitment into the lung and airspace.

PMID- 7730643
TI  - Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8
      induces destruction of cartilage and production of IL-1 and IL-1 receptor
      antagonist in vivo.
AB  - Whether or not IL-8 attracts T lymphocytes and activates neutrophils in vivo
      remains unclear. Most studies on function of IL-8 in vivo have been done on human
      IL-8 in heterologous animals. To elucidate the role of IL-8 in vivo, we injected
      homologous IL-8 into rabbit knee joints and investigated the inflammatory
      response. Injection of 10 micrograms of rabbit IL-8 induced a massive
      accumulation of neutrophils. IL-8 attracts T lymphocytes in vitro; however,
      rabbit IL-8 induced no appreciable lymphocyte accumulation in rabbits. Although
      human IL-8 was reported not to induce cartilage destruction when injected into
      heterologous animals, we observed that rabbit IL-8 did provoke a release of
      neutrophil elastase, leading to cartilage destruction, when injected into
      rabbits. An inhibitor against neutrophil elastase (ONO-5046) prevented
      destruction of the cartilage. Injection of rabbit IL-8 induced bioactive and
      immunoreactive IL-1 beta and IL-1 receptor antagonist (IL-1Ra) in the joint
      cavity. Immunohistochemistry showed that IL-1 beta and IL-1Ra positive cells were
      infiltrating leukocytes. In neutrophil-depleted rabbits, rabbit IL-8 induced far
      lesser concentrations of IL-1 beta and IL-1Ra and no cartilage destruction
      compared with findings in normal rabbits. Thus, the infiltrating neutrophils are
      the main producers of these cytokines and are responsible for the cartilage
      destruction. In addition to neutrophil chemotactic activity, IL-8 proved to have
      a neutrophil-activating capability in vivo, with respect to release of neutrophil
      elastase and induction of IL-1 beta and IL-1Ra.

PMID- 7730644
TI  - Characterization of a complement receptor 2 (CR2, CD21) ligand binding site for
      C3. An initial model of ligand interaction with two linked short consensus repeat
      modules.
AB  - Human CR2 (CD21, EBV receptor) is an approximately 145-kDa receptor and a member
      of the regulators of complement activation gene family. Regulators of complement
      activation proteins are characterized by the presence of repeating motifs of 60
      to 70 amino acids that are designated short consensus repeats (SCR). CR2 serves
      as a receptor for four distinct ligands. Three of these ligands (complement C3,
      gp350/220 of EBV, and CD23) interact with the amino terminal 2 of 16 SCR (SCR 1
      and 2). Previous studies have determined that at least four sites are important
      in allowing CR2 to efficiently bind EBV. Two of these sites are also important
      for binding mAb OKB7, a reagent that blocks both EBV and iC3b/C3dg binding to
      CR2. We have identified and characterized important sites of iC3b ligand binding
      by utilizing human-mouse CR2 chimeras, a rat anti-mouse CR2 mAb designated 4E3
      that blocks receptor binding to C3, and human CR2-derived peptides. In addition
      to demonstrating an important role for the same sequence in SCR 1 that is part of
      the mAb OKB7 and EBV binding site, we have identified a new region within SCR 2
      that interacts with C3. These results, when compared with a model of a dual SCR
      solution structure derived from human factor H SCR, predict that two distinct
      largely surface-exposed sites on CR2 interact with iC3b. A relative twist of 130
      degrees about the long axis of the second SCR in this model would be necessary
      for these sites to form a single patch for iC3b binding on CR2.

PMID- 7730645
TI  - Dexamethasone up-regulates A3 adenosine receptors in rat basophilic leukemia (RBL
      2H3) cells.
AB  - The cross-linking of surface IgE receptors by multi-functional Ags promotes the
      degranulation of mast cells. Previous studies have indicated that the nucleoside
      adenosine potentiates this response by activating putative A3 adenosine receptors
      (AR) coupled to phospholipase C in mast cells or their cultured analogues, rat
      basophilic leukemia (RBL-2H3) cells. Moreover, it has been shown that exposure of
      RBL-2H3 cells to dexamethasone attenuated antigen-mediated mast cell
      degranulation, but potentiated the response elicited by adenosine. To determine
      whether the A3AR is a potential site of action of dexamethasone, we have assessed
      the status of these receptors in RBL-2H3 cells treated with and without
      dexamethasone. Treatment with dexamethasone (100 nM) for 24 h resulted in an
      increase in the number of A3AR to 217 +/- 50% of control. The increased receptor
      expression was both time- and concentration-dependent, with optimal increases
      observed following 16 h of treatment and using 100 nM of dexamethasone. No
      increase in the level of the A2aAR was detectable following dexamethasone
      treatment. Northern blotting studies indicated a 2.7 +/- 0.3-fold increase in
      A3AR mRNA in RBL-2H3 cells treated with dexamethasone for 24 h. Dexamethasone
      also increased the expression of G protein alpha i2, alpha i3, alpha s, and beta
      subunits by two- to threefold. Activation of the A3AR by
      aminophenylethyladenosine (APNEA) following dexamethasone treatment enhanced the
      production of inositol phosphates and the mobilization of intracellular Ca2+.
      From these data, it is concluded that dexamethasone increases the expression of
      both A3AR and G proteins in RBL-2H3 cells which contributes to the enhanced
      response to adenosine.

PMID- 7730646
TI  - Anti-inflammatory effects of an adenosine kinase inhibitor. Decreased neutrophil
      accumulation and vascular leakage.
AB  - Adenosine inhibits neutrophil function, but also causes cardiovascular side
      effects when administered systemically. To regulate local adenosine
      concentrations and minimize toxicity, a novel adenosine kinase inhibitor, GP-1
      515, was tested in several acute inflammation models in rats. GP-1-515 inhibited
      carrageenan-induced rat paw swelling in a dose-dependent manner (maximum
      inhibition, 47 +/- 3%). In a rat skin lesion model, GP-1-515 significantly
      reduced cutaneous neutrophil infiltration following an intradermal injection of
      carrageenan or zymosan-activated plasma, or induction of a reverse passive Arthus
      reaction. This action appeared to be mediated by endogenous adenosine, inasmuch
      as a specific A2 adenosine receptor antagonist reversed the effect. GP-1-515 also
      decreased vascular leakage induced by carrageenan (which is partly neutrophil
      dependent) and by the neutrophil-independent mediators histamine and bradykinin.
      Inhibition of leakage was reversed by co-administration of adenosine receptor
      antagonist. Treatment with anti-inflammatory doses of GP-1-515 had no effect on
      heart rate or blood pressure. In conclusion, GP-1-515 significantly reduced both
      neutrophil infiltration and vascular leakage through the release of endogenous
      adenosine without evidence of cardiovascular side effects.

PMID- 7730647
TI  - Granulocyte activation via a binding site near the C-terminal region of
      complement receptor type 3 alpha-chain (CD11b) potentially involved in
      intramembrane complex formation with glycosylphosphatidylinositol-anchored Fc
      gamma RIIIB (CD16) molecules.
AB  - We report that engagement of a particular epitope near the C-terminal region of
      complement receptor type 3 (CR3, CD11b/CD18) alpha-chain with CD11b mAb VIM12
      induces granulocyte activation with a rise in cytosolic-free Ca2+, actin
      polymerization, an up-regulation of CR3 cell surface expression and enhanced
      adhesiveness. Induction of enhanced adhesiveness and homotypic aggregation of
      human granulocytes represents an active process. It is temperature and energy
      dependent, requires divalent cations, and an intact cytoskeleton. The mAb VIM12
      induced enhanced adhesiveness seems to be mediated, at least in part, by
      activated CR3 molecules. It can be significantly inhibited, although not
      completely abolished, with blocking mAbs against adhesiotopes of CR3. VIM12
      induced adhesion could be blocked with the serine/threonine inhibitors okadaic
      acid and calyculin A and with dibuturyl-cAMP but not with the protein kinase
      inhibitors herbimycin A and staurosporine. We further present evidence that the
      particular molecular region of CR3 recognized by mAb VIM12 might be involved in
      the reported intramembrane sugar-lectin type interaction and complex formation
      between transmembrane CR3 and glycosylphosphatidylinositol (GPI)-anchored Fc
      gamma RIIIB (CD16) molecules on human granulocytes. Binding of mAb VIM12 to CR3
      on granulocytes enhances the release of GPI-anchored Fc gamma RIIIB molecules
      from granulocytes upon phosphoinositol-phospholipase C treatment. The sugar
      preparation N-acetyl-D-glucosamine, previously shown to dissociate CR3-Fc gamma
      RIIIB complex formation, inhibits mAb VIM12 binding. Engagement of CR3 with mAb
      VIM12 may thus mimic a biologically relevant intramembrane cooperation between
      two distinct receptor molecules on human granulocytes.

PMID- 7730648
TI  - Inherited human complement C5 deficiency. Nonsense mutations in exons 1 (Gln1 to
      Stop) and 36 (Arg1458 to Stop) and compound heterozygosity in three African
      American families.
AB  - Hereditary C5 deficiency has been reported in several families of different
      ethnic backgrounds and from different geographic regions, but the molecular
      genetic defect causing C5 deficiency has not been delineated in any of them. To
      examine the molecular basis of C5 deficiency in the African-American population,
      the exons and intron/exon boundaries of the C5 structural genes from three C5
      deficient (C5D) African-American families were sequenced, revealing two nonsense
      mutations. The nonsense mutations are located in exon 1 (C84AG to TAG) in two of
      the C5D families (Rhode Island and North Carolina) and in exon 36 (C4521GA to
      TGA) in the third C5D family (New York). The exon 1 and 36 mutations are
      contained in codons that encode the first amino acid of the C5 beta-chain (Gln1
      to Stop) and residue 1458 in the alpha-chain (Arg1458 to Stop), respectively.
      Allele-specific PCR and sequence analyses demonstrated that the exon 1 mutation
      is present in only one of the C5 null genes in both the Rhode Island and North
      Carolina families, and the exon 36 mutation is contained in only one C5 null gene
      in the New York family. Neither of the nonsense mutations was found in the
      European or Caucasian-American C5D individuals examined. Collectively, these data
      indicate that: 1) C5 deficiency is caused by several different molecular genetic
      defects, 2) C5 deficiency in the African-American population can be explained in
      part by two distinct nonsense mutations in exons 1 and 36, and 3) compound
      heterozygosity exists in all of the reported African-American C5D families.

PMID- 7730649
TI  - Quantitation of tryptase, chymase, Fc epsilon RI alpha, and Fc epsilon RI gamma
      mRNAs in human mast cells and basophils by competitive reverse transcription
      polymerase chain reaction.
AB  - Competitive reverse transcription-PCR assays developed for human tryptase,
      chymase, Fc epsilon RI alpha, and Fc epsilon RI gamma mRNA molecules were applied
      to the HMC-1 leukemic mast cell line, the KU812 leukemic basophil cell line, mast
      cells dispersed from lung and skin, and peripheral blood basophils. Relative
      amounts of alpha-tryptase and beta-tryptase mRNA were determined by analysis of
      BseAI digests of PCR products. Tryptase expression was highest in tissue-derived
      mast cells, lowest in basophils and KU812 cells, and intermediate in HMC-1 cells.
      beta-Tryptase mRNA predominated in HMC-1 and KU812 cells; mixtures of alpha- and
      beta-tryptase were found in tissue mast cells; and alpha-tryptase predominated in
      basophils. Chymase mRNA was more abundant in skin-derived (nearly all of the MCTC
      type) than lung-derived (variable amounts of MCTC and MCT cells) mast cells.
      Small amounts of chymase mRNA were detected in HMC-1 cells; none was found in
      basophils, in KU812 cells, or in the one preparation of 100% MCT cells derived
      from lung. Comparable amounts of Fc epsilon RI alpha and Fc epsilon RI gamma mRNA
      molecules were measured in basophils and tissue-derived mast cells, lesser
      amounts were detected in KU812 cells, and almost none was detected in HMC-1
      cells. Thus, steady state levels of the granule and membrane resident molecules
      examined in our study are transcriptionally regulated in mast cells and
      basophils.

PMID- 7730650
TI  - IL-8 is expressed by human peripheral blood eosinophils. Evidence for increased
      secretion in asthma.
AB  - Eosinophils possess the capacity to synthesize various cytokines. We demonstrate
      that IL-8 mRNA and protein are constitutively expressed by freshly isolated
      resting human eosinophils. Most of the patients with bronchial asthma or atopic
      dermatitis show evidence for up-regulated IL-8 protein expression in eosinophils
      but not in neutrophils, suggesting that an eosinophil-specific cytokine may act
      in these patients. To investigate whether the intracellular IL-8 can be released,
      eosinophils were stimulated by different cytokines and platelet-activating
      factor. Priming with granulocyte-macrophage CSF and a subsequent 25-min
      stimulation with RANTES or platelet-activating factor resulted in release of IL-8
      from highly purified human eosinophils in vitro. As the eosinophil is the
      predominant cell in asthmatic inflammation, we determined IL-8 concentrations in
      bronchoalveolar lavage fluids from normal individuals and asthmatic patients.
      Bronchoalveolar lavage fluids from patients with bronchial asthma consistently
      demonstrated high IL-8 concentration compared with the controls. This suggests
      that IL-8 is released in vivo by inflammatory bronchial cells in asthma.

PMID- 7730651
TI  - A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory
      cytokine production and immune responses.
AB  - In vitro, IL-10 inhibits T cell proliferation and LPS-induced monocyte production
      of IL-1, TNF-alpha, IL-6, and IL-8. We studied the safety and immunomodulatory
      effects of IL-10 administration in humans. Seventeen healthy volunteers received
      a single i.v. bolus injection of either human IL-10 (1, 10, or 25 micrograms/kg)
      or placebo. Routine safety parameters, lymphocyte phenotypes, T cell
      proliferative responses, and stimulus-induced cytokine production were assessed
      before and 3, 6, 24, and 48 h after injection. There were no adverse symptoms or
      signs after IL-10 administration. A transient neutrophilia and monocytosis that
      peaked at 6 h (45-160% above base line) was observed. However, lymphocyte counts
      fell by 25% 3 and 6 h after the injection (p < 0.01). In particular, lymphocytes
      expressing the T cell surface markers CD2, CD3, CD4, CD7, and CD8 were
      significantly decreased. Mitogen-induced T cell proliferation was suppressed by
      up to 50% (p < 0.01) in the two higher dose groups. Significant dose-dependent
      inhibition (65-95%) of TNF-alpha and IL-1 beta production from whole blood
      stimulated ex vivo with endotoxin occurred after each dose of IL-10. In contrast,
      there was no reduction in the production of their respective antagonists, TNF
      soluble receptor p55 or IL-1 receptor antagonist. We conclude that a single
      intravenous injection of IL-10 is safe in humans, has inhibitory effects on T
      cells, and suppresses production of the pro-inflammatory cytokines TNF-alpha and
      IL-1 beta.

PMID- 7730652
TI  - Effects of stress on immune cell distribution. Dynamics and hormonal mechanisms.
AB  - Immune cell trafficking is crucial to the performance of the surveillance as well
      as effector functions of the immune system. Because immune cells travel between
      tissues through the bloodstream, the numbers and proportions of leukocytes in the
      circulation provide an important representation of the state of leukocyte
      distribution in the body. The studies described here examine significant and
      selective changes in numbers and percentages of peripheral blood leukocyte
      subpopulations in the rat. These changes were rapidly induced under conditions of
      mild acute stress. Stress-induced increases in plasma corticosterone were
      accompanied by a significant decrease in numbers and percentages of lymphocytes,
      and by an increase in numbers and percentages of neutrophils. flow cytometric
      analysis revealed that B cell, NK cell, and monocyte numbers showed a greater
      stress-induced decrease than did T cells. All stress-induced changes were
      observed during the light (inactive) as well as the dark (active) period of the
      animal's diurnal cycle. Importantly, the stress-induced changes in leukocyte
      numbers and percentages were rapidly reversed upon the cessation of stress.
      Furthermore, the effects of stress were largely dependent on adrenal hormones,
      because the magnitude of the stress-induced changes was significantly reduced in
      adrenalectomized animals. Moreover, administration of corticosterone to
      adrenalectomized animals resulted in a close replication of stress-induced
      changes observed in adrenal-intact animals. These results suggest that endocrine
      factors released during stress modulate leukocyte trafficking and result in the
      redistribution of leukocytes between the blood and other immune compartments.
      Such a redistribution may significantly affect the ability of the immune system
      to respond to potential or ongoing immune challenge.

PMID- 7730653
TI  - Use of anti-CD3 epsilon F(ab')2 fragments in vivo to modulate graft-versus-host
      disease without loss of graft-versus-leukemia reactivity after MHC-matched bone
      marrow transplantation.
AB  - The use of T cell-specific mAb in vivo for prevention and treatment of graft-vs
      host disease (GVHD) and its impact on graft-vs-leukemia (GVL) reactivity was
      examined in a murine model of MHC-matched bone marrow transplantation (BMT).
      F(ab')2 fragments of a CD3 epsilon-specific mAb were administered to irradiated
      AKR (H-2k) hosts after transplantation of BM plus spleen cells from B10.BR donors
      (BMS chimeras). The effects on GVH and GVL reactivity were Ab dose- and schedule
      dependent. A short course of mAb (qe2d, days 0 to 8) prevented clinical evidence
      of GVHD and mortality. Anti-CD3 F(ab')2 mAb reversed clinical symptoms of acute
      GVHD when delayed up to 18 days post-transplant. Anti-host (Mls-1a)-specific V
      beta 6+ cells were absent from the spleens of GVH-negative control mice, but
      persisted in Ab-treated BMS chimeras despite the absence of GVHD. Leukemic mice
      given 16.7 micrograms of Ab on days 0, 2, and 4 survived leukemia-free without
      developing severe GVHD. A longer course of Ab completely prevented GVHD, but led
      to leukemia relapse in tumor-bearing hosts, despite engraftment of donor T cells.
      The GVL effect was quantitatively stronger when Ab was used for GVH therapy as
      compared with GVH prevention. Some Ab-treated, GVH-free chimeras relapsed with
      lymphomas in unusual sites, suggesting that occult tumor cells may persist in
      nonlymphoid tissues. These experiments demonstrate that T cell-specific mAb can
      be used successfully in vivo to avoid severe GVHD, but that excessive or ill
      timed administration of Ab may eliminate GVL reactivity.

PMID- 7730654
TI  - Analysis of apoptosis in lymph nodes of HIV-infected persons. Intensity of
      apoptosis correlates with the general state of activation of the lymphoid tissue
      and not with stage of disease or viral burden.
AB  - The occurrence of in vivo apoptosis was investigated in lymph node sections
      obtained from HIV-infected persons at different stages of disease. The degree of
      apoptosis in lymph nodes from HIV-infected individuals was compared with that
      observed in lymph nodes obtained from HIV-negative individuals. Apoptosis was
      readily detected in lymph nodes obtained from both HIV-negative and HIV-positive
      persons; however, the degree of apoptosis in lymph nodes obtained from HIV
      positive persons was three to four times higher than that observed in the lymph
      nodes obtained from HIV-negative persons. In contrast to HIV-negative lymph nodes
      in which apoptosis was confined largely to germinal centers, in HIV-positive
      lymph nodes all functional compartments of the lymph node (i.e., cortex,
      paracortex, and sinuses) were extensively involved by this phenomenon.
      Furthermore, a significant correlation was observed between intensity of
      apoptosis and degree of activation of the lymphoid tissue associated with HIV
      infection. In contrast, intensity of apoptosis correlated neither with the
      clinical stage of HIV disease nor with the viral burden in the lymph node.
      Finally, apoptosis was not restricted only to CD4+ T cells; both B cells and CD8+
      T cells were found to undergo apoptosis. Taken together, these results indicate
      that the increased intensity of the apoptotic phenomenon in HIV infection is
      caused by the general state of immune activation, and is independent of the
      progression of HIV disease and of the levels of viral load.

PMID- 7730655
TI  - Aspartate at position 57 of nonobese diabetic I-Ag7 beta-chain diminishes the
      spontaneous incidence of insulin-dependent diabetes mellitus.
AB  - MHC class II genes have been shown to influence the development of the autoimmune
      disease insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic (NOD)
      mouse. In human IDDM it has been suggested that the presence of an aspartate at
      position 57 of the DQ beta-chain might be important in determining resistance to
      development of IDDM. The involvement of MHC class II genes in IDDM was
      investigated through the introduction of MHC encoding transgenes. We show that
      introduction of a mutated I-Ag7 Ab gene which encodes an aspartate at position 57
      reduces the incidence of IDDM but does not prevent insulitis, sialadenitis, or
      the development of insulin and nuclear autoantibodies.

PMID- 7730656
TI  - Analysis of Ig VH region genes encoding IgE antibodies in splenic B lymphocytes
      of a patient with asthma.
AB  - An atopic patient with hypersensitivity against house dust mite died as a result
      of an asthmatic attack. A portion of the spleen was obtained and was used to
      analyze the spectrum of Ig heavy chain V regions involved in encoding IgE Abs. A
      nested PCR technique generated 14 cloned VH sequences that had distinct CDR3
      regions; 5 of 14 were derived from the minor VH5 family, and the remainder
      derived from the larger families, VH3 (6 of 14) and VH4 (3 of 14). One of the VH3
      derived sequences was present as a repeated sequence in three clones. A control
      PCR with the same VH primers in combination with JH primers yielded only 1 of 13
      sequences from VH5, indicating preferential VH5 usage only for IgE. Analysis of
      VH5-C epsilon sequences revealed usage of a single gene, DP73, with extensive
      mutations and several "hot spots" containing common replacement amino acids.
      However, there was no concentration of replacement mutations in the CDRs, which
      conventionally would indicate a role for Ag selection. The VH3 and VH4 genes in
      combination with C epsilon also harbored extensive somatic mutations. From these
      findings in splenic B lymphocytes, and those of a previous study of blood
      lymphocytes, it seems that preferential usage of VH5 genes and extensive somatic
      hypermutation are characteristic of B cells synthesizing IgE in patients with
      allergic disease.

PMID- 7730657
TI  - Simian immunodeficiency virus (SIV)-specific CTL in cerebrospinal fluid and
      brains of SIV-infected rhesus macaques.
AB  - Simian immunodeficiency virus (SIV)-specific CD8+ CTL were isolated from blood,
      cerebrospinal fluid, and brains of rhesus macaques infected i.v. with SIV. CTL
      were found as early as 1 wk postinfection and their appearance correlated with a
      decrease of viral Ag (p27) found in the blood. CTL isolated from cerebrospinal
      fluid and/or brain often recognized different viral proteins than CTL isolated
      from blood, suggesting either a unique migratory pattern to the central nervous
      system or a difference in activation/retention of lymphocytes in these
      compartments.

PMID- 7730658
TI  - Administration of noncytolytic IL-10/Fc in murine models of lipopolysaccharide
      induced septic shock and allogeneic islet transplantation.
AB  - Numerous studies have suggested the potential application of IL-10 as an anti
      inflammatory and as an antirejection agent. Unfortunately, cytokines have short
      circulating t1/2 We developed a murine IL-10/Fc gamma 2a immunoligand that
      possesses the biologic functions of IL-10 and the long circulating t1/2 in vivo,
      characteristic of Igs. We mutated the Fc gamma 2a fragment to render the
      immunoligand ineffective in directing Ab-dependent cell-mediated cytotoxicity and
      complement-directed cytolysis (noncytolytic IL-10/Fc (IL-10/Fc2-)). In terms of
      IL-10 activity, IL-10/Fc2- was as effective as rIL-10 mole per mole in preventing
      lethal septic shock, but the immunoligand had a prolonged period of efficacy in
      accord with its extended circulating half-life. Contrary to expectations, IL
      10/Fc2- treatment tended to accelerate the destruction of islet cell allografts
      and increase the levels of granzyme B gene expression in local draining lymph
      nodes. These data suggest that the enhanced cytotoxic activity of allograft
      destroying CTLs may contribute to the accelerated allograft rejection. Finally,
      our studies suggest that a noncytolytic IL-10/Fc fusion protein provides a useful
      tool to study the biologic effects of IL-10 in vivo and may provide a useful
      agent for the prevention and treatment of septic shock.

PMID- 7730659
TI  - Gene knock-out technology: a methodological overview for the interested novice.
AB  - Gene targeting by homologous recombination is a powerful technique, generating
      mouse strains with defined mutations in their genome. These genetically modified,
      'designer' animals allow us for the first time to ask simple questions about
      elaborate and complex biological systems. Dissecting the function of individual
      components of the immune system is a perfect application of this technology.
      Although the techniques involved in the generation of gene knock-out mice are
      increasingly well defined, to many immunologists the language and concepts are
      confusing. This review presents the essentials of the technology in a form
      digestible by the non-expert.

PMID- 7730660
TI  - Difficulties in obtaining monoclonal antibodies to subsets of human leukocytes,
      using neonatal tolerance induction in mice.
AB  - Many antigens are shared between different types of human leukocytes. In an
      effort to obtain new lineage-specific monoclonal antibodies, particularly
      antibodies to dendritic cells, we attempted to tolerize newborn mice to one type
      of leukocyte and then immunize the adults with another. We found that T cells,
      either unstimulated T cells or T blasts, were more effective at inducing neonatal
      tolerance than non-T cells or B cell lines. However, the tolerance that was
      achieved was not restricted to T cells, since we could not elicit from the
      tolerized mice a specific antibody response to a B cell line or to blood
      dendritic cells. Here we describe several efforts, all unsuccessful, to achieve
      cell specific immune responses in tolerant mice. The parameters we considered
      included the type of cell used to tolerize neonatal mice, the regimen of
      injections for inducing tolerance or eliciting immunity, and the use of several
      different adjuvants.

PMID- 7730661
TI  - A monoclonal antibody against Meningococcus group B polysaccharides used to
      immunocapture and quantify polysialylated NCAM in tissues and biological fluids.
AB  - Polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) are
      transiently expressed in many tissues during development and in discrete areas of
      the adult central nervous system. In pathological situations, they are expressed
      by poorly differentiated tumor cells of neuroectodermal origin and by
      regenerating muscle. An ELISA is introduced here to estimate the relative
      concentrations of PSA-NCAM expressed by tissues or released into biological
      fluids. In this double-sandwich assay, an anti-PSA antibody (anti-MenB) was
      adsorbed onto plastic plates and permitted the immunocapture of PSA-bearing
      molecules. It is demonstrated that these molecules are major NCAM. The second
      antibody was directed against an amino acid sequence shared by NCAM isoforms in
      several species. The standard curves were established using Nonidet P40 extracts
      of human or mouse embryonic brain known to be rich in PSA-NCAM. The sensitivity
      of the assay allows for quantitation of PSA-NCAM in muscle during regeneration
      and in small samples of cerebrospinal fluid from patients with medulloblastoma
      metastasis.

PMID- 7730662
TI  - Directional cloning of an oligonucleotide fragment into a single restriction
      site.
AB  - Oligonucleotide fragments can be directionally subcloned into vectors at a single
      restriction site. By using T4 DNA polymerase exonuclease activity to treat vector
      DNA, single-stranded ends can be generated. The oligonucleotide sequences are
      designed to have sequence complementary to these single-stranded ends. Through
      the homologous annealing of oligonucleotides to the treated vector ends, the
      successfully subcloned molecules forms a circular recombinant DNA that is ready
      for transformation. There is no sequence restriction at the ends of the DNA
      fragment. All restriction site ends are accessible to this method. This approach
      for oligonucleotide fragment insertion and together with our previously described
      general method of exonuclease induced DNA subcloning provide convenient methods
      for the construction of recombinant DNA.

PMID- 7730663
TI  - Early detection of apoptosis in defined lymphocyte populations in vivo.
AB  - Recently many methods have been developed for the detection of apoptosis.
      However, all of them have some limitations in determining whether specific
      subsets of cells are undergoing apoptosis. In this paper we describe a technique
      in which one simultaneously stains for cell surface markers with fluorescent
      monoclonal antibodies and for nuclear DNA breaks using in situ DNA nick
      translation detectable by fluorescence. The method has been evaluated using
      radiation-induced programmed cell death of lymphocytes and compared with some
      other techniques. It was found that the method is very specific and sensitive. It
      enabled us to enumerate apoptotic cells at the single cell level and
      simultaneously determine their subset-specific surface antigen profile both in
      vivo and in vitro. It is also insensitive to nicks present in replicating cells.
      Our data suggest that this method may be useful for the study of programmed cell
      death of antigen specific T cells in vivo.

PMID- 7730664
TI  - Isolation of an IL-13-dependent subclone of the B9 cell line useful for the
      estimation of human IL-13 bioactivity.
AB  - A novel sub-clone of the B9 hybridoma cell line (B9-1-3) has been selected by
      cloning following continuous culture in rhIL-13. This cell line shows an
      increased sensitivity to both hIL-13 and mIL-4 compared to the parental B9 cell
      line. The proliferative response to IL-13 can be blocked with an anti-IL-4
      receptor monoclonal antibody but not with the soluble IL-4 receptor, suggesting
      that IL-13- and IL-4-binding receptor subunits are distinct but form part of a
      common receptor complex. Although the B9-1-3 cell line is still sensitive to
      picogrammes of IL-6, it can be used to measure IL-13 in the presence of IL-6 by
      inclusion of excess neutralizing IL-6 antibody. This cell line should thus prove
      useful both in measuring the IL-13 bioactivity and for the dissection of the
      molecular nature of the IL-13:IL-4 receptor complex.

PMID- 7730665
TI  - Stability of monoclonal IgM antibodies freeze-dried in the presence of trehalose.
AB  - We describe the use of the disaccharide trehalose for stabilization of mouse
      monoclonal IgM antibodies during freeze-drying and prolonged storage at elevated
      temperatures. Spent culture media, ascitic fluids and isolated immunoglobulins
      were freeze-dried in the presence of trehalose, stored at different temperatures,
      and tested after rehydration for their binding to their corresponding antigens.
      Antibodies, directed against various types of antigens, effectively recovered
      their binding efficiency as tested in enzyme-linked immunoassays, flow cytometry
      and immunofluorescence. Application of trehalose for freeze-drying of labile
      monoclonal IgM antibodies permits convenient long-term storage of large
      quantities of antibodies, facilitates their transport at ambient temperature and
      simplifies the construction of pre-aliquoted kits based on such antibodies.

PMID- 7730666
TI  - Method for quantitation of IgG subclass antibodies in mouse serum by enzyme
      linked immunosorbent assay.
AB  - One of the methods for calibration of antigen specific antibodies in a serum
      involves parallel titration of known concentrations of purified normal
      immunoglobulins (Igs) and a specific antiserum. We evaluated the effect of three
      methods for capturing known concentrations of purified normal mouse Igs (IgG, IgG
      subclasses and IgM) on the anti-tetanus toxoid antibody concentrations assigned
      to a reference mouse serum: (1) direct coating, (2) capture by pre-coated anti
      mouse IgG (Fc) specific antibodies, and (3) capture by pre-coated anti-mouse IgG
      (Fab) specific antibodies. Direct coating of purified Igs onto plastic was the
      least efficient and would greatly overestimate antigen specific antibody
      concentrations. Equivalent concentrations of purified IgG subclasses and IgM
      produced higher absorbances when captured by anti-Fab antibodies pre-coated on
      plates than by anti-Fc antibodies. As a consequence, the anti-Fc capture method
      resulted in the assignment of IgG1, IgG2a and IgG2b tetanus specific antibody
      concentrations which exceeded the total IgG1, IgG2a and IgG2b concentrations.
      Additionally, the sum of tetanus specific IgG subclass antibodies exceeded the
      tetanus specific IgG antibody concentration by > 2-fold. In contrast, the anti
      Fab capture method resulted in 2-9-fold lower assigned tetanus antibody
      concentrations which did not exceed the total Ig concentrations. We conclude that
      when using enzyme-linked immunosorbent assays, parallel titration of purified
      normal Ig standards captured by anti-Fab antibodies is superior to anti-Fc
      capture or direct coating for calibrating antigen specific antibodies in a
      reference serum.

PMID- 7730667
TI  - A direct non-competitive idiometric enzyme immunoassay for serum oestradiol.
AB  - We report a novel non-competitive enzyme immunoassay for oestradiol based on the
      use of two types of anti-idiotypic antibody that recognize different epitopes
      within the hypervariable region of the primary anti-oestradiol idiotypic antibody
      (Ab1). The first anti-idiotype, the betatype, competes with the analyte for an
      epitope of the primary antibody at the binding site. On the other hand, the
      second anti-idiotype, the alphatype, binds to the Ab1 in the presence of analyte
      but does not bind to the betatype/Ab1 complex because of steric hindrance. In the
      present format the biotinylated alphatype was captured onto anti-biotin IgG which
      was adsorbed on the surface of microtitre wells. Reaction mixtures containing the
      Ab1 complexed sequentially with an enzyme labelled second antibody reagent, with
      oestradiol standards or serum samples and with the betatype anti-idiotypic
      antibody were then allowed to react with the immobilized alphatype anti-idiotypic
      antibody. The enzyme activity of the bound fraction measured at 405 nm increased
      with increasing oestradiol concentrations over the range 0.06-2.5 ng/ml. The
      detection limit of the assay was 28 pg/ml. The intra-assay variation ranged from
      3.5 to 12.4%, and inter-assay variation from 6 to 13.4%. The results obtained by
      the colorimetric idiometric immunoassay correlated well with those obtained by a
      direct radioimmunoassay (n = 85, r = 0.97). This non-competitive immunoassay,
      termed idiometric assay, for haptens permits the development of sensitive
      immunoassays with a wide working range, and a variety of end-point determinations
      depending on the label used (e.g., enzyme, chemiluminescent or fluorogenic
      compound).

PMID- 7730668
TI  - The humanized severe combined immunodeficient mouse as a model for primary human
      humoral response against HIV1 peptides.
AB  - Adequate animal models for the study of human immunodeficiency virus (HIV)
      infection are important for the analysis of specific cellular and humoral immune
      responses. Humanized severe combined immunodeficiency (SCID) mice can be
      constructed either by injecting human peripheral blood lymphocytes (hu-PBL-SCID)
      or by transplanting human fetal tissues--liver, thymus and bone fragments--(SCID
      hu) into these mice. Such animals can produce human immunoglobulins and SCID-hu
      mice exhibit circulating T and B lymphocytes of human origin. These humanized
      mice were injected with immunogenic HIV peptides and the specific humoral
      response was studied. A human antibody response was obtained after de novo
      contact with HIV1 peptides p583 and p642, from gp41. In SCID-hu mice, a primary,
      then a secondary response were demonstrated to occur with 225 mg/l of human
      immunoglobulin (Ig)M and 300-1860 mg/l human IgG. When tested in ELISA, these
      human antibodies recognized specifically both the immunization peptides and the
      HIV1 antigens. The antibody response was obviously of a primary nature since the
      human cells derived from naive fetal cells. When SCID mice received
      intraperitoneal injections of human peripheral blood lymphocytes pre-incubated in
      vitro with peptide p583 for 1 week, and when the resulting hu-PBL-SCID mice were
      injected with the same peptide, only IgM anti-HIV antibodies were produced (372
      424 mg/l) and the switch to IgG antibodies did not occur. This model may provide
      a means to produce human monoclonal antibodies to HIV and to check candidate HIV
      vaccines.

PMID- 7730669
TI  - [The role of immunotherapy in metastatic cancer of the kidney].
AB  - Nearly 2,500 new cases of metastatic renal cell carcinoma are diagnosed in France
      every year. Only immunotherapy has demonstrated some therapeutic responses, owing
      to antitumoral activity of T lymphocytes, CDS and also CD4. This review
      illustrates results from different therapeutic regimen with interferon alpha,
      interleukin-2 (intravenous or subcutaneous), alone or in association, and
      adoptive immunotherapy with in vitro activated lymphocytes. Response rates ranged
      from 15 to 30%, with a 10% complete response rate. High level of serum
      interleukin-6 and C-reactive protein predicted unfavorable evolution and lack of
      response to immunotherapy. Improvement in the response rate needs the selection
      of patients who are potentially responder and new therapeutic association,
      especially interleukin-2, interferon alpha and 5-fluoro-uracil.

PMID- 7730670
TI  - [Traumas of the ureter. Apropos of 29 cases].
AB  - The origin of ureteral trauma is often iatrogenic, particularly after
      gynaecologic surgery, and causes diagnostic and therapeutic problems. The
      characteristics of this affection are reviewed in a retrospective study of 29
      traumatic lesions of the ureter collected over a 17 year period. Three ureteral
      trauma were by penetrating injury and twenty six were iatrogenic. For the latter,
      hysterectomy was the principal cause (17 cases). Urine leakage through the vagina
      was the most frequent clinical symptom (20 cases). In the majority of cases,
      intravenous urography was sufficient to make the diagnosis. Uretero
      hydronephrosis was noticed in 17 cases, and extravasation in 14 cases. The
      majority of iatrogenic lesions (20 cases) was diagnosed after a one month delay.
      Lower third of the ureter was the most frequent site of injury in iatrogenic
      traumas (10 cases), whereas the upper third was the site of predilection of
      penetrating traumas (3 cases). Four vesico-vaginal fistulaes and two resto
      vaginal fistulaes were associated to ureteral iatrogenic lesions. Various
      therapeutic methods were used. For mid and lower ureteral lesions, psoas-bladder
      hitch was the most frequent procedure (11 cases). On the other hand, for upper
      ureteral lesions, ureteral anastomosis was done in three cases. Only one
      nephrectomy was done, after an iatrogenic lesion diagnosed very late, with a non
      functioning kidney. We noticed six surgical failures: four after termino-terminal
      anastomosis, and two after Boari-Kuss's procedure. The data of literature
      concerning etiopathogeny, diagnosis, therapeutic modalities and prevention of
      traumatic lesions of the ureter and reviewed.

PMID- 7730671
TI  - [Is a complementary treatment necessary in case of positive surgical ranges after
      radical prostatectomy?].
AB  - While it is known that radical prostatectomy is not a curative procedure, would
      be logical to propose a possible adjuvant treatment. Unfortunately it does not
      appear that adjuvant radiotherapy significantly improves total survival.

PMID- 7730672
TI  - [Cancer of the penis in Tunisia. Apropos of 3 cases].
AB  - The authors report 3 cases of penile carcinoma seen over a 15 year period. They
      analyse features related to epidemiology, etiopathogeny, diagnosis and treatment,
      and review the literature on this affection.

PMID- 7730673
TI  - [A case of association of cyst of the urachus and Meckel's diverticulum].
AB  - Meckel diverticulum and residual urachus have a common embryological origin: the
      yolk sac at the eight day of life. Their course is independent but the underlying
      mechanisms are identical. Meckel diverticulum occurs in 2 to 4% of the
      population. Clinical signs are often absent and complications occur in 4% of the
      cases (haemorrhage, occlusion, inflammation, and rarely tumoural formation).
      Residual urachus occurs as a cystic formation, a sinus or a fistulization and may
      degenerate into adenocarcinoma of severe prognosis. The reported association has
      not apparently been reported previously in the literature. Due to the risk of
      cancerization, it is suggested that residual urachus should be searched in cases
      of Meckel diverticulum.

PMID- 7730674
TI  - [Fenestration by laparoscopic approach of a post-transplantation renal
      lymphocele].
AB  - Symptomatic post-transplantation renal lymphoceles are usually treated with
      Byron's technique--medical laparotomy, internal drainage with fenestration,
      transperitoneal marsupialization and epiploplasty. The same procedure was
      performed laparoscopically in a 34 year old obese man who had a renal
      transplantation 18 months earlier. The procedure, together with its advantages
      are discussed.

PMID- 7730675
TI  - [Intermittent hydronephrosis].
AB  - Intermittent hydronephrosis is a frequent cause of obstruction in the
      ureteropelvic junction in the adult. Diagnosis is based on intravenous
      pyelography, echography and renal scintigraphy with or without hyperdiuresis. We
      report a case of intermittent hydronephrosis successively affecting both kidneys.

PMID- 7730676
TI  - [Urology in the female 1993-1994: an uro-gynecologic perspective].

PMID- 7730677
TI  - The diagnostic value of exercise echocardiography in ischemic heart disease in
      relation to quantitative coronary arteriography.
AB  - The aim of the study was to assess the diagnostic value of bicycle exercise
      echocardiography using quantitative coronary arteriography as a reference.
      Exercise echocardiography was performed in 70 consecutive patients referred for
      coronary angiography. Digital loops were obtained at rest, peak, and immediately
      after exercise in the standard views (parasternal long and short axis, apical two
      and four chamber views). Wall motion analysis was made on the basis of the 16
      segment model, scoring each segment from 3 (hyperkinesia) to -1 (hypokinesia).
      Exercise echocardiography was considered positive when wall motion in at least
      one segment decreased at least one score from rest to peak or post exercise.
      Cinefilms were evaluated using automated quantitative coronary arteriography
      software. Transstenotic pressure gradients were calculated based on flow
      assumptions at the maximal stenosis flow reserve. Pressure losses > 30 mmHg and
      quantitatively measured percent diameter stenosis of > 50% were considered
      clinically significant. Stenoses in the equivocal range of 40-69% were subjected
      to separate analysis. Exercise echocardiography was superior to exercise-induced
      ST-segment depression in the diagnosis of coronary artery disease. In the overall
      sample of 70 patients, the sensitivity of exercise echocardiography against
      percent diameter stenosis was 84%, against pressure gradient 86%. The specificity
      against these two parameters was 86% and 84%, respectively. When analysing the
      subgroup of 40-69% stenoses (N = 14), sensitivity of exercise echocardiography
      against percent diameter stenosis was 67%, against pressure gradient 88%. The
      specificity against these two parameters was 100% and 84%, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7730678
TI  - Computer simulation of the propagation of contrast medium in a coronary artery
      during one cardiac cycle.
AB  - In some angiographic methods for measurement of mean coronary flow in ml/min, a
      threshold is applied to 'concentration-distance' curves obtained from a constant
      rate injection by computing the intravascular contrast medium concentration along
      the main coronary branches. If the shape of the velocity profile would remain
      parabolic throughout the cardiac cycle, the correct threshold value would be '50%
      of the concentration at the injection site'. But, coronary flow being strongly
      pulsatile, the shape of the velocity profile must be expected to vary appreciably
      within the cardiac phase. In order to investigate if a single, appropriate
      threshold value nevertheless exists for a great variety of coronary flow pulses
      and velocity profiles, the spreading of contrast medium injected continuously in
      a tube perfused by a time varying flow Q(t) was studied by computer simulation.
      While the particular time courses of flow and velocity profile appear to be of
      secondary importance, the ratio 'injection rate to peak coronary flow' has a
      major impact. If it is equal to or greater than 1, a threshold value of 47% is
      the best choice. If the ratio is markedly less than 1, no appropriate threshold
      exists and use of the 47% threshold will result in considerable flow
      underestimations. This was fully confirmed by measurements of absolute coronary
      flow performed in patients.

PMID- 7730679
TI  - Transesophageal echocardiographic determinants of embolism in nonrheumatic atrial
      fibrillation.
AB  - The purpose of the study was to determine the relation of transesophageal
      echocardiographic findings to symptoms of systemic embolism in patients with
      nonrheumatic atrial fibrillation. Transthoracic and transesophageal
      echocardiography were used to study 107 patients with atrial fibrillation
      including 49 patients without embolic complications and 58 patients who had
      suffered from previous cerebral or peripheral embolism. A multiple logistic
      regression analysis revealed that left atrial thrombi (odds ratio 9.0, 95% CI 2.4
      33.6, p < 0.005) and the presence of dense left atrial spontaneous contrast (odds
      ratio 8.4, 95% CI 1.3-53.1, p < 0.05) were independently related to embolic
      symptoms. Intensive left atrial spontaneous contrast was associated with an
      increased left atrial diameter (odds ratio 2.0, 95% CI 1.1-3.6, p < 0.05), the
      presence of chronic atrial fibrillation (odds ratio 6.9, 95% CI 1.6-29.8, p <
      0.01) and aortic atherosclerosis (odds ratio 2.6, 95% CI 1.2-5.5, p < 0.05). It
      was further negatively correlated to mitral regurgitation (odds ratio 0.4, 95% CI
      0.2-0.9, p < 0.05). In conclusion, dense spontaneous echo contrast and left
      atrial thrombi are associated to thromboembolic complications in patients with
      nonrheumatic atrial fibrillation. Classifying of spontaneous contrast seems to be
      useful when estimating the thromboembolic risk in atrial fibrillation.

PMID- 7730680
TI  - What is the most appropriate variable for estimation of mean pulmonary capillary
      wedge pressure by transesophageal pulsed Doppler echocardiography?
AB  - Although left ventricular (LV) inflow and pulmonary venous (PV) flow variables
      estimated by transesophageal Doppler echocardiography (TEE) reflect pulmonary
      capillary wedge pressure (PCWP), they are also affected by changes in cardiac
      function. The purpose of the present study was to detect the most appropriate
      variable for the estimation of PCWP by TEE in patients (pts) with ischemic heart
      disease. Several variables of LV inflow and left upper PV flow were compared with
      PCWP in 36 pts (six with angina pectoris and 30 with old myocardial infarction).
      Early diastolic flow (E) and atrial contraction flow (A) were used as LV inflow,
      while systolic forward flow (X), diastolic forward flow (Y) and atrial
      contractile reversal flow (z) were used as PV flow. The peak velocity of each
      flow wave (Ep, Ap, Xp, Yp, and Zp) and the time-velocity integral (Ei, Ai, Xi,
      Yi, and Zi) were measured. The ratio of Ep to Ap (Ep/Ap), Ei to Ai (Ei/Ai), Xp to
      Yp (Xp/Yp), Xi to Yi (Xi/Yi), Zp to Ap (Zp/Ap), Zi to Ai (Zi/Ai) and the systolic
      fraction of PV forward flow were calculated. Among these variables, the Zi/Ai
      ratio was most strongly correlated with PCWP (R = 0.80). The Zi/Ai ratio may not
      be influenced by atrial function because the augmentation of atrial pump function
      increases Zi as well as Ai, and this may be one reason why the ratio correlated
      well with PCWP. CONCLUSION: The Zi/Ai ratio is a new useful variable for
      estimating PCWP by TEE.

PMID- 7730681
TI  - Left ventricular opacification after intravenous injection of Albunex. The effect
      of different administration procedures.
AB  - A clinical study has been performed to investigate the influence of different
      administration procedures on the degree of contrast enhancement of the left
      ventricle. The administration variables assessed included Albunex injection rate,
      arm position, flushing rate and flushing fluid. Twenty-four healthy male
      volunteers were included. Compared to an injection rate of 1 ml/sec an injection
      rate of Albunex of 2 ml/sec caused an earlier appearance of contrast in the right
      ventricle (1 heart beat), whereas transpulmonary passage was not influenced.
      Horizontal arm position caused a delay in time to peak intensity of 2 to 3 heart
      beats in both systole and diastole as compared to elevated arm position.
      Injection rate of 1 ml/sec compared to 2 ml/sec caused a higher peak intensity
      and mean area under the curve and a longer mean time to peak intensity and
      transit time. Differences varied from 6 to 230 grey level units out of mean
      values of 2500. All the observed differences were small and thus probably of no
      clinical importance. The present study indicates that improvements in the
      pressure stability characteristics of the albumin microspheres in Albunex have
      been achieved. This implies that a simple administration procedure can be used.
      It is recommended that the contrast agent, after resuspension, is injected
      through a three-way stop cock cannula, followed by 10 ml of saline for flushing.
      The cannulas or syringes used should be no smaller than 20 G. The injection rate
      should be 1-2 ml/sec, depending on the diameter of the cannula. By using this
      procedure, a reliable transpulmonary passage and left ventricular opacification
      may be obtained.

PMID- 7730682
TI  - Effect of respiration on Doppler parameters of normal tricuspid porcine
      bioprosthetic valves.
AB  - The Doppler indexes of tricuspid porcine bioprosthetic valves were evaluated in
      twelve patients without clinical and two-dimensional echocardiographic evidence
      of valve dysfunction. Peak and mean pressure gradients across the prostheses were
      measured using the simplified Bernoulli equation. All the Doppler measurements
      were compared during inspiration and expiration. During inspiration peak
      velocity, peak gradient and mean gradient (1.52 +/- 0.28 m/s; 9.7 +/- 3.05 mmHg;
      4.07 +/- 1.16 mmHg) were significantly higher than during expiration (1.28 +/-
      0.8 m/s; 6.58 +/- 2.7 mmHg; 2.98 +/- 1.13 mmHg; p < 0.01) but pressure half time
      was not significantly different (122 +/- 62 ms versus 134 +/- 75 ms; p > 0.05).
      Inspiratory range of peak velocities, peak gradients, mean gradients and pressure
      half times were respectively 0.8-2.04 m/s; 4.9-16.6 mmHg; 1.2-7.2 mmHg; 42-340 ms
      while expiratory range of values was 0.8-1.93 m/s; 2.6-15 mmHg; 1.1-5.7 mmHg; 46
      345 ms. These data suggest that even very long pressure half times do not
      indicate valve dysfunction. This study demonstrates that large variation of
      Doppler parameters are present during respiration and could produce inaccuracy in
      the assessment of bioprostheses in tricuspid position if they are not taken in
      consideration.

PMID- 7730683
TI  - Computation of left ventricular volume curves from gated blood pool studies
      without explicit use of edge detection algorithms: concise communication.
AB  - A new technique has been developed to compute left ventricular (LV) time activity
      curves from gated blood pool (GBP) studies without the use of manual,
      semiautomated or fully automated edge detection algorithms. The method utilizes
      the correlation of entropy calculated from the counts of a fixed region of
      interest covering the left ventricle during a cardiac cycle to compute the LV
      volume curve for a new patient. The new LV volume curve is obtained through
      interpolation of those volume curves of a data base which are associated with the
      closest variations in normalized entropy to the new one. The computed LV time
      activity curves agree with those obtained from manual or fully automated outlines
      of the left ventricle within 9 percent for the selected set of 67 patients
      demonstrating the potential of the method. The accuracy of calculated LV volume
      curves can be improved theoretically to any degree by increasing the number of
      cases in the data base of known statistical feature vectors associated with the
      LV images and LV volume curves. The new method for computation of LV curves is
      very efficient and robust when compared to traditional techniques.

PMID- 7730684
TI  - Mood states of oncology outpatients: does pain make a difference?
AB  - The purposes of this study were to determine if there were significant
      differences in the mood states of oncology outpatients who had cancer-related
      pain and those who were pain free, and to evaluate the relationships between pain
      intensity and duration and mood states in those patients with pain. Two hundred
      (54.2%) patients experienced cancer-related pain during the previous month and
      169 (45.8%) patients were pain free. Those patients who experienced cancer
      related pain scored significantly higher on all of the subscale scores of the
      Profile of Mood States, except vigor, and had a significantly higher total mood
      disturbance (TMD) score than did pain-free patients. In addition, the subscale
      scores of tension, depression, anger, fatigue, confusion, and TMD scores were
      moderately correlated with increases in pain intensity. Also, depression,
      fatigue, confusion, and TMD scores were moderately correlated with increasing
      duration of pain. These data suggest that there is a relationship between pain
      and mood in oncology outpatients and that health-care professionals need to
      assess for mood disturbances in this population and develop appropriate treatment
      strategies.

PMID- 7730685
TI  - Neuropsychiatric syndromes and psychological symptoms in patients with advanced
      cancer.
AB  - This article represents the contributions of the panel on "Neuropsychiatric
      Syndromes and Psychological Symptoms" of the National Cancer Institute of Canada
      Workshop on Symptom Control and Supportive Care in Patients with Advanced Cancer.
      The panel's presentations focused on mood disorders and cognitive disorders, and
      described the current state of knowledge regarding prevalence, assessment, and
      intervention. Recommendations for future research are presented based on a
      consensus of the panel as to the need to fill glaring gaps in our current state
      of knowledge, and a desire to improve the quality of research in this area of
      palliative medicine. Recommendations for future research on neuropsychiatric
      symptoms and syndromes in palliative care include (1) adoption of uniform
      terminology (taxonomy of disorders) and diagnostic classification systems, (2)
      utilization of existing validated tools and measures in prevalence and
      intervention research, (3) development of new tools and measures that are more
      applicable and relevant to the palliative care setting, (4) encouragement for
      studies of the prevalence of neuropsychiatric symptoms and syndromes, (5)
      promotion of intervention studies utilizing pharmacologic and nonpharmacologic
      treatments for depressive disorders and cognitive disorders in advanced cancer
      patients, and (6) expansion of the focus of such research to other
      neuropsychiatric disorders (for example, anxiety disorders, posttraumatic stress
      disorders, and sleep disorders), symptoms (fatigue and tension) and related
      issues (suicidal ideation and desire for hastened death).

PMID- 7730686
TI  - Cachexia-anorexia-asthenia.
AB  - The National Cancer Institute (Canada) sponsored a workshop on symptom control in
      Banff, Alberta, in October 1993. This article reports on the workshop
      recommendations for research on one symptom complex, the cachexia-anorexia
      asthenia syndrome. In addition to encouraging study generation, the
      recommendations provide a baseline for assessing the scope and strength of future
      Canadian research initiatives on cachexia-anorexia-asthenia.

PMID- 7730687
TI  - Cardiovascular autonomic insufficiency in a patient with metastatic malignancy.
AB  - A case of cardiovascular autonomic insufficiency is described in a cachectic 70
      year-old man with widely metastatic small-cell tumor. The patient experienced
      disabling syncopal episodes in association with severe postural hypotension.
      Tests of cardiovascular autonomic insufficiency were abnormal. The introduction
      of fludrocortisone and the use of elastic stockings produced palliation of the
      symptomatology, but his condition deteriorated and he died. Autopsy demonstrated
      unexpectedly extensive tumor invasion of autonomic nervous tissue. Although
      cardiovascular autonomic insufficiency (CAI) has been described in association
      with malignancy and malnutrition, local tumor invasion of autonomic nervous
      tissue and radiation injury may have been other possible, albeit unusual,
      etiologic factors. This case illustrates the differential diagnosis of
      hypotension and CAI in patients with advanced metastatic malignancy and also
      emphasizes the need for autopsy studies when speculating as to the cause of CAI
      in this group of patients.

PMID- 7730688
TI  - A pain syndrome associated with large adrenal metastases in patients with lung
      cancer.
AB  - We report two cases of a pain syndrome caused by large adrenal metastases in
      patients with lung cancer. A review of the literature identified 23 previously
      reported patients with primary lung cancers who appear to have had a similar
      syndrome, although in none of these cases were other likely causes of the pain
      syndrome carefully excluded. The syndrome characteristically includes unilateral
      flank pain but may have abdominal components as well, and has only been reported
      in patients with large metastases (> or = 5 cm in largest diameter). Although the
      mechanism by which large adrenal metastases cause the pain syndrome is not clear,
      we suggest that treatment that includes local anesthetic agents or steroids may
      be effective. The pain syndrome caused by large adrenal metastases is not
      included in reviews of cancer pain syndromes but needs to be considered in the
      differential diagnosis of patients with lung cancer and flank or abdominal pain.

PMID- 7730689
TI  - Methylphenidate for the management of somatization in terminal cancer patients.
AB  - We report a case that illustrates methylphenidate's (MP) usefulness in the
      management of psychological distress and associated somatization in the
      palliative-care setting. A 60-year-old man affected by terminal cancer of the
      prostate had been complaining of increasing physical pain, without any evidence
      of significant disease progression, opioid toxicity, or previous history of drug
      addiction. Because of patient's denial, the team had been unsuccessful in
      identifying any potential emotional factors affecting his physical suffering. MP
      could both counteract opioid-induced sedation and improve pain control through a
      positive action on patient's mood. In spite of a rapid development of tolerance,
      which required a subsequent escalation in MP daily doses, the drug was well
      tolerated and the patient could die in good physical comfort 2 weeks later.

PMID- 7730690
TI  - Dronabinol as a treatment for anorexia associated with weight loss in patients
      with AIDS.
AB  - The effects of dronabinol on appetite and weight were evaluated in 139 patients
      with AIDS-related anorexia and > or = 2.3 kg weight loss in a multi-institutional
      study. Patients were randomized to receive 2.5 mg dronabinol twice daily or
      placebo. Patients rated appetite, mood, and nausea by using a 100-mm visual
      analogue scale 3 days weekly. Efficacy was evaluable in 88 patients. Dronabinol
      was associated with increased appetite above baseline (38% vs 8% for placebo, P =
      0.015), improvement in mood (10% vs -2%, P = 0.06), and decreased nausea (20% vs
      7%; P = 0.05). Weight was stable in dronabinol patients, while placebo recipients
      had a mean loss of 0.4 kg (P = 0.14). Of the dronabinol patients, 22% gained > or
      = 2 kg, compared with 10.5% of placebo recipients (P = 0.11). Side effects were
      mostly mild to moderate in severity (euphoria, dizziness, thinking
      abnormalities); there was no difference in discontinued therapy between
      dronabinol (8.3%) and placebo (4.5%) recipients. Dronabinol was found to be safe
      and effective for anorexia associated with weight loss in patients with AIDS.

PMID- 7730691
TI  - [Risk of chromosomally unbalanced progeny in prenatal diagnoses of reciprocal
      translocation carrier].
AB  - To obtain new criteria for presuming the existence of chromosomally unbalanced
      progeny in reciprocal translocation carrier couples, the obstetrical histories of
      57 couples were analysed. The chromosomally unbalanced progeny who had been
      prenatally or postnatally diagnosed were mainly partial trisomies. In contrast
      with partial trisomies, there were only a few cases of partial monosomies and
      there were only two cases of chromosomal imbalance derived from 3:1 segregation
      in gametogenesis. Moreover, the percentage of haploid autosome length (%HAL) of
      the maternal carriers whose progeny had suffered from chromosomal imbalance was
      significantly smaller than those of the maternal carriers who had not had progeny
      with chromosomal imbalance. Based on these results, the following criteria were
      obtained: 1) Partial trisomies tend to be maintained in pregnancy but partial
      monosomies do not; Most chromosomally unbalanced zygotes which were induced by
      3:1 segregated gametes tend to be spontaneously selected in early pregnancy; 3)
      When interchanged segments of chromosomes are small in maternal reciprocal
      translocation carriers, chromosomally unbalanced fetuses tend to be maintained in
      pregnancy.

PMID- 7730692
TI  - [Influence of endotoxin on sensitivity to oxytocin in pregnant rat myometrium].
AB  - In order to clarify the mechanism of preterm labor induced by intrauterine
      infection, we studied the effect of endotoxin on oxytocin sensitivity of the
      myometrium in the pregnant rat. We administrated bacterial endotoxin obtained
      from Escherichia coli to the pregnant rat at preterm. By using a myometrial
      strip, we determined the effect of oxytocin on contractility, production of
      prostaglandins (PGs) and phosphoinositide hydrolysis. 1. Endotoxin increased
      myometrial sensitivity to oxytocin in the pregnant rat at preterm. The pD2 value
      was equal to that of myometrium taken from term pregnant rat. This
      hypersensitivity was significantly inhibited by indomethacin. 2. In the
      myometrial strips from rats to which endotoxin was administered, the
      concentrations of PGF2 alpha and PGE2 had already developed a tendency to
      increase during spontaneous contractions, when compared to the controls. There
      was seen a significant additional increase due to oxytocin. PGF2 alpha production
      was also significantly inhibited by indomethacin. 3. Oxytocin significantly
      stimulated total inositol phosphate production in a dose-dependent manner in
      myometrium taken from preterm pregnant rat. The inositol 1.4.5-trisphosphate
      production stimulated by oxytocin significantly increased in comparison to the
      controls. These results suggest that not only the production of PGs but
      phosphoinositide hydrolysis of transmembrane signaling pathways would play an
      important role in the mechanism of myometrial contraction at preterm when
      intrauterine bacterial infection developed.

PMID- 7730693
TI  - [Study on insulin resistance evaluated by glucose tolerance test in obese
      pregnant women].
AB  - This study examined the plasma glucose level and immunoreactive insulin (IRI)
      level in the course of 75g oral glucose tolerance test (OGTT) during pregnancy in
      27 obese women (pre-pregnant body mass index (BMI) > = 24kg/m2) and 53 non-obese
      women (BMI < 24kg/m2). In women with normal glucose tolerance, the fasting IRI
      level, IRI area under a 3-h curve during 75gOGTT (IRI-AUC) and the net increase
      in IRI areas above fasting values under a 3-h curve (delta IRI-AUC) in 15 obese
      women were higher than those in 47 non-obese women (p < 0.01, p < 0.05, p <
      0.03), but there was no difference between the two groups in the fasting plasma
      glucose level, BS-AUC or delta BS-AUC. In women with abnormal glucose tolerance,
      the fasting IRI level in 12 obese women was higher than that in 6 non-obese women
      (p < 0.01), but there were no significant differences in the other factors. The
      fasting IRI level was correlated with the fasting plasma glucose level, BS-AUC,
      IRI-AUC and BMI (p < 0.002, p < 0.001, p < 0.0001, p < 0.0001). These results
      show that there is a higher insulin level and lower systemic sensitivity to
      insulin in obese women than in non-obese women in all groups.

PMID- 7730694
TI  - [Effect of progesterone, cortisol and dehydroepiandrosterone-sulfate on
      prostaglandin production by cultured human myometrial cells].
AB  - Prostaglandins (PGs) are considered to play important roles as contraction
      regulating factors in the mechanism of human uterine contraction. On the other
      hand, steroid hormones released in large amounts in late pregnancy appear to be
      closely related to the maintenance of pregnancy, fetal growth, and onset of
      delivery. To clarify the interactions between PGs and steroid hormones, we
      studied PGE2 and 6-keto-PGF1 alpha production on human myometrial cell culture.
      Cultures of myometrial cells from premenopausal patients with benign uterine
      diseases were established, and PG production in serum-free media and in the
      presence of various concentrations of progesterone (P), cortisol (F) and
      dehydroepiandrosterone-sulfate (DHAS) was studied. The following results were
      obtained: 1) The PGE2 and 6-keto-PGF1 alpha concentrations were 1,410.4pg/ml and
      600pg/ml at 10 minutes after changing the medium, decreased transiently at 30-60
      minutes, and increased thereafter. 2) When the cells were cultured with various
      concentration of P for 24 hours, PGE2 production was suppressed in the presence
      of P at 10(-7)M or above, but 6-keto-PGF1 alpha production showed a significant
      dose-dependent increase. 3) In the presence of F, PGF2 production shows a dose
      dependent increase at high doses, but 6-keto-PGF1 alpha production markedly
      decreases at 10(-6)M or above. 4) In the presence of DHAS, PGE2 production
      increased markedly at 10(-6)M or above. These findings indicate that steroid
      hormones are regulatory factors in the production of PG by the myometrium.

PMID- 7730695
TI  - [Clinical and pathological study of 24 patients with fallopian tube malignancy].
AB  - Clinical and pathological analyses were carried out in 24 patients with fallopian
      tube malignancy. The results are as follows: 1. Twenty-three patients had
      adenocarcinoma (well differentiated 11, moderately 6, poorly 6) and one patient
      had MMT (Mullerian mixed tumors). 2. There were 11 cases in stage I, 4 in stage
      II, 8 in stage III and 1 in stage IV according to Dodson's classification. 3.
      Atypical genital bleeding was the most common symptom, whereas 12.5% of patients
      had no symptoms. 4. Positive rates in cytology were 25.0% in cervico-vaginal
      smear and 55.0% in endometrial aspiration cytology. 5. The overall 5-year
      survival rate is 60.0%. The 5-year survival rates for stage I/II and stage III/IV
      were 88.9% and 16.7%, respectively. 6. The relapse rate of 16 patients treated
      with complete surgery was 25.0% (well differentiated 11.1%, moderately 0%, poorly
      75.0%). Based on these observation, it is likely that patients with stage I/II
      have a good prognosis, however, patients with poorly differentiated
      adenocarcinoma have a high relapse rate, indicating that intensive adjuvant
      chemotherapy would be necessary in these cases. Cytologic examination,
      particularly endometrial aspiration cytology, is an effective method to use in
      detecting cases with fallopian tube malignancy early.

PMID- 7730696
TI  - [Prognostic evaluation of endometrial carcinoma by DNA content and histologic
      factors].
AB  - Paraffin-embedded tumor samples from 51 endometrial cancer patients were analyzed
      by DNA flow cytometry to investigate relationship between DNA content and
      histologic prognostic factors. Twenty of the tumors were DNA aneuploid. With
      regard to clinical stage, DNA aneuploid tumors were observed in 22.9% of stage I,
      72.7% of stage II and 80.0% of stage III cases. Concerning the histologic type,
      DNA aneuploid tumors were seen in 31.4% of endometrial carcinomas, 28.6% of
      adenosquamous cell carcinomas and 87.5% of serous adenocarcinoma cases. As to the
      depth of invasion, in 16.0% of cases there was invasion within 1/3 myometrium, in
      42.9% of cases the middle 2/3, and in 80.0% of cases there was invasion
      throughout 2/3, these all being aneuploid cases. The above findings suggest that
      DNA aneuploidy is associated with the clinical stage, myometrial invasion and
      especially the histologic type. Furthermore, lymph node metastasis was detected
      in 3.4 and 26.3% of DNA diploid and aneuploid groups, respectively, and the
      frequencies were significantly different. Moreover, the 5 year survival rate was
      significantly higher in the DNA diploid group (96.8%) than in the aneuploid group
      (62.7%) (p < 0.05). The results suggest that flow cytometric ploidy determination
      is useful in making the prognosis for patients with endometrial carcinoma.

PMID- 7730697
TI  - [Detection technique of aneuploidy in uncultured amniocytes using amplified
      fluorescent in situ hybridization].

PMID- 7730698
TI  - [Clinical study on the usefulness of sairei-to for the infertile patients with
      positive autoantibody].

PMID- 7730699
TI  - [A case report of a combined intrauterine and tubal pregnancy after natural
      ovulatory cycle--early diagnosis by transvaginal ultrasonography].

PMID- 7730700
TI  - [A case report: squamous cell carcinoma of the uterine body].

PMID- 7730701
TI  - [Two cases of myotonic dystrophy diagnosed by DNA analysis].

PMID- 7730702
TI  - [Diagnosis of intrauterine disorders by sonohysterography].

PMID- 7730703
TI  - Are 18 doses of WHO/MDT sufficient for multibacillary leprosy; results of a trial
      in Malawi.
AB  - A trial comparing 18 monthly and 30 monthly doses of the World Health
      Organization-recommended multidrug therapy (WHO/MDT) in 305 multibacillary
      leprosy patients in Malawi is described. Patients were randomly allocated to one
      of the two regimens at the time of taking the 18th supervised dose of WHO/MDT.
      The mean follow-up period was 3 years (maximum 6 years). No relapse was observed
      in either group. The cumulative probabilities of remaining slit-skin smear
      positive were significantly higher among patients receiving only the 18 monthly
      doses of WHO/MDT, but reached zero at month 60 of follow up. The percentage of
      patients who developed new disabilities during the trial period was similar in
      both groups. However, the overall percentage of patients who developed new
      disabilities (50/305, 16.4%) remains disturbingly high. On the whole, the results
      of the trial argue in favor of 18 monthly doses of WHO/MDT taken within 24 months
      as being sufficient for the treatment of multibacillary leprosy.

PMID- 7730704
TI  - An unusual spreading phenomenon in an artificial medium inoculated with M.
      leprae.

PMID- 7730705
TI  - Mycobacterium leprae in the epidermis: ultrastructural study I.

PMID- 7730706
TI  - Detection of AFB in tuberculoid biopsies.

PMID- 7730707
TI  - Polyaxonal myelination in a human leprous nerve.

PMID- 7730708
TI  - Enhanced response of serum IgG class of anti-PGL-I antibodies in leprosy patients
      during onset and following clinical remission of type 1 and type 2 reactions.

PMID- 7730709
TI  - Erythema nodosum leprosum in Malaysians.

PMID- 7730710
TI  - Follicular keratoses in leprosy and post-kala-azar dermal leishmaniasis.

PMID- 7730711
TI  - Successful treatment of a lepromatous patient with clarithromycin.

PMID- 7730712
TI  - Ocular leprosy: do steroids complicate matters?

PMID- 7730713
TI  - Patient treatment compliance in leprosy; an unjustifiably critical review.

PMID- 7730714
TI  - Incidence of late lepra reaction among multibacillary leprosy patients after MDT.
AB  - Multidrug therapy (MDT) recommended by the World Health Organization (WHO) had
      been administered in 1982 to a cohort of multibacillary (MB) leprosy patients.
      Treatment was administered for a minimum period of 2 years or until skin-smear
      negativity for acid-fast bacilli was achieved (whichever was later). Among 980 MB
      leprosy patients who completed treatment, 11 patients (1.1%) experienced lepra
      reactions during surveillance. Probable predictive factors are discussed. The
      incidence of lepra reaction seemed to be three times more common in borderline
      (BL) leprosy than in lepromatous (LL) leprosy. The majority of these events
      occurred during the first 3 years of surveillance. All of these episodes were
      treated with steroids without antileprosy chemotherapy. None of these patients
      was confirmed as experiencing a relapse during the subsequent period of
      surveillance.

PMID- 7730715
TI  - Doppler sonography of vertebral arteries and audiovestibular system investigation
      in leprosy.
AB  - Thirty-six patients with leprosy and 12 sex- and age-matched controls were
      investigated for disorders of the audiovestibular system, and vertebral artery
      measurements were calculated using a color Doppler ultrasound technique.
      Sensorineural hearing loss found to be of cochlear origin was detected in 8 of
      the leprosy patients. Maximal flow velocity and mean flow velocity were measured,
      and the total vertebral artery flow was calculated by adding flows from the right
      and left sides. There was a significant reduction in the total maximal peak flow
      velocity of the vertebral artery of the lepromatous patients compared to the
      controls. Doppler sonography of the vertebral artery gave useful information
      about some pathology seen in lepromatous patients.

PMID- 7730716
TI  - Optimal pH for preserving the activity of Mycobacterium leprae during incubation
      of cells in a cell-free liquid medium.
AB  - The effect of the pH of a cell-free liquid medium on the activity of
      Mycobacterium leprae during incubation of the cells was investigated. As a
      parameter for evaluating the activity, the amount of adenosine triphosphate (ATP)
      extracted from the incubated cells collected by centrifugation was measured. The
      results demonstrate that the activity of M. leprae cells was maintained at a
      significant level for approximately 4 weeks at 30 degrees C in 0.05 M phosphate
      buffer containing 10% fetal calf serum at pH 7.0 compared to cells at other pHs
      tested, but activity was not preserved in phosphate buffer at pH 7.0 without
      serum and incubated at 37 degrees C. The maintenance of the activity under these
      conditions was prolonged somewhat by the addition of glycerin (2%) to the medium,
      and was definitely inhibited by rifampin but not by either penicillin or
      isoniazid. From the results reported here, it could be postulated that the
      optimal pH of cell-free media for the study of cultivation of M. leprae is 7.0.

PMID- 7730717
TI  - Clinical utility of LSR/A15 gene for Mycobacterium leprae detection in leprosy
      tissues using the polymerase chain reaction.
AB  - Skin biopsy and slit-skin smears from 46 leprosy patients and 4 nonleprosy
      patients were tested for the presence of Mycobacterium leprae by the polymerase
      chain reaction (PCR) using primers based on the sequence of the LSR/15 kD gene.
      The PCR was found to be specific and sensitive, with a detection level of 10 and
      100 bacilli. PCR using skin biopsies gave a higher detection rate than did slit
      skin smears, probably due to the higher density of bacilli in a 4-mm punch
      biopsy. Dot blot hybridization with radioactive probes was 10-fold more sensitive
      than the ethidium bromide staining. Eight patients who did not show acid-fast
      bacilli in tissues by the conventional methods were shown to have PCR-amplified
      M. leprae DNA. False-negative results were obtained in 3 cases even though formal
      evidence for tissue inhibitors was absent.

PMID- 7730718
TI  - Application of polymerase chain reaction for the detection of Mycobacterium
      leprae DNA in specimens from treated leprosy patients.
AB  - In this study of leprosy patients apparently cured by dapsone monotherapy, the
      polymerase chain reaction (PCR), one of the most reliable and sensitive DNA-based
      assays, was used for the specific detection of Mycobacterium leprae DNA. Sputum
      and slit-skin samples from 44 such patients at Baba Baghi Leprosy Sanatorium in
      Iran were examined. Primers for a 530-base-pair fragment of the gene encoding the
      36-kDa antigen of M. leprae were used for the study. The PCR results were
      compared with microscopy for acid-fast bacilli. Of the 44 sputum samples, 2 were
      positive by PCR (4.5%) and of the 44 slit-skin swabs taken from the same
      patients, 10 were PCR positive (22.7%). Only one patient was PCR positive for
      both sputum and slit-skin specimens (2.3%). No positive results were found by
      acid-fast microscopy. In total, 11 of 44 (25%) patients in this study were found
      to be PCR positive for M. leprae, and it was thought probable that this indicated
      the presence of live organisms. Particularly interesting was the statistically
      significant association of positive results from slit-skin swabs with
      paucibacillary rather than multibacillary leprosy. It is suggested that whereas
      relapse or immunological reaction in paucibacillary disease may result from
      surviving organisms, in multibacillary leprosy this may be due to re-infection.

PMID- 7730719
TI  - Analysis of vaccines prepared from armadillo-derived M. leprae; results of an
      inter-laboratory study coordinated by the World Health Organization. Immunology
      of Mycobacterial Diseases (IMMYC) Steering Committee, World Health Organization.
AB  - Preparations of armadillo-derived Mycobacterium leprae used in vaccine trials
      were analyzed using a combination of morphological, chemical and immunological
      criteria. When compared to more recent preparations, vaccine lots prepared in
      1984 and 1985 were found to contain fewer intact bacilli and lower amounts of M.
      leprae antigens. These differences may be characteristic of the original
      preparations, or alternatively, may have arisen during prolonged storage. The
      early vaccine lots were those used in the recently published Venezuela trial.

PMID- 7730720
TI  - Identification and purification of armadillo (Dasypus novemcinctus)
      immunoglobulins: preparation of specific antisera to evaluate the immune response
      in these animals.
AB  - In this work we describe the purification and characterization of armadillo
      immunoglobulins. The IgM was precipitated using low-strength ionic solution and
      further purified by filtration through Sephadex G-200. The IgG was obtained in
      pure form by precipitation of serum with ammonium sulfate and DEAE-cellulose ion
      exchange chromatography. The purity of these immunoglobulins was evaluated by
      polyacrylamide gel electrophoresis. The results showed 28-kDa light chains and 55
      kDa and 70-kDa heavy chains for IgG and IgM, respectively. The rabbit antibodies
      against these molecules were used to prepare fluorescein (FITC) and peroxidase
      conjugates. The FITC conjugate was used to quantify IgM-bearing lymphocytes. An
      average of 17% of peripheral blood lymphocytes were sIgM+ from 14 healthy
      animals. Additionally, in the same animals we quantified lymphocytes with the
      capacity to form rosettes with sheep red-blood cells; the average for this marker
      was 10%. Also, the production of crossreacting antibodies to BCG was evaluated in
      healthy and Mycobacterium leprae-inoculated animals using the peroxidase
      conjugates. All animals with active infection recognized BCG antigens.

PMID- 7730721
TI  - Inter-observer variability in the assessment of nerve function in leprosy
      patients in Ethiopia.
AB  - One of the major problems in leprosy is to detect any change in nerve function
      early enough so as to increase the chances of recovery and prevent disability.
      Several tests have been developed to assess nerve function and are used in
      leprosy control programs worldwide, but they are frequently performed by
      different workers on different occasions and under variable conditions. In this
      study we investigated the variability between different groups of observers in
      the assessment of nerve function in leprosy patients in Ethiopia. Sensory
      function was assessed by using a set of nylon monofilaments (NF) and a ball-point
      pen (BP), and motor function was assessed by using voluntary motor testing (VMT).
      We also studied the variability between observers in the assessment of the
      clinical signs of neuritis. Duplicate measurements were performed in random order
      on 50 leprosy patients by two physio-technicians and on 50 other patients by two
      health assistants. The percent agreement between observers was calculated for
      each single nerve, and weighted kappa statistics were used to assess whether
      agreement was better than expected due to chance alone. Systematic differences
      between observers were evaluated using the Wilcoxon signed rank test. On sensory
      testing, inter-observer variability was found to be related to the training and
      experience of the observer, to the nerve tested, and to the neurological status
      of the patient. When tests were performed by physio-technicians, we observed 32%
      to 58% agreement with the NF test and 71% to 84% agreement with the BP test,
      measured on different scales. After weighting for the scale difference, the
      agreement seemed comparable with these methods but the differences in
      measurements with the BP test were found to be dependent upon the neurological
      status of the patient. The variability between observers differed according to
      the nerve tested, and there was some evidence of systematic differences between
      observers with both methods. When performed by the health assistants, agreement
      was between 34% and 46% with the NF and between 66% and 82% with the BP tests.
      After weighting for the scale difference, the agreement seemed comparable but the
      BP was not liable to the systematic differences seen in the NF results. These
      differences could be attributed to the differences in the experience of the
      workers with these tests. With the VMT, small variability between observers was
      found for all nerves tested, except the facial nerve, when performed by both the
      physio-technicians and by the health assistants (72% to 98% agreement).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7730722
TI  - Inflammatory bone changes in leprous skeletons from the medieval Hospital of St.
      James and St. Mary Magdalene, Chichester, England.
AB  - The extent and location of an inflammatory bone lesion, periostitis, were
      examined in 50 leprous skeletons from the Chichester cemetery of the Hospital of
      St. James and St. Mary Magdalene in Sussex, England. Although the presence of
      periostitis is not pathognomonic of leprosy, it predominantly indicates dermal
      and neuropathic changes that the patient would have presented in life. The spread
      of inflammation across the knee joint and the ossification of the interosseous
      membrane due to inflammation are also suggested.

PMID- 7730723
TI  - Minocycline in lepromatous leprosy.
AB  - Twelve patients were treated with three dose levels of minocycline for 30 days,
      primarily to detect the dose-related effects on Mycobacterium leprae viability,
      followed by another 5 months of daily minocycline for overall efficacy and
      persistence of clinical and antibacterial effects. Subsequently, the patients
      were given standard WHO/MDT chemotherapy for multibacillary leprosy. Clinical
      improvement was recognizable during the first month, occurring much earlier among
      those on minocycline 200 mg daily than those who received minocycline 100 mg
      daily. A similar change also was observed in one patient 11 days after three
      daily doses of 100 mg of minocycline. At the end of 6 months, all patients were
      clinically improved with a slight reduction in the average bacterial index (BI)
      and logarithmic index of bacilli in biopsy (LIB). The effects of minocycline on
      viability by mouse foot pad inoculation and palmitic acid oxidation assays were
      noted beginning at 10 to 14 days of daily dosing and becoming more definite after
      30 days of treatment. Both tests correlated fairly well. Doses of 200 mg daily
      did not appear to be more efficient than minocycline 100 daily. Phenolic
      glycolipid-I (PGL-I) antigen determinations done on some patients during the
      first month remained positive and did not correlate with changes in viability
      results. At the end of 6 months, after 5 months of 100 mg of minocycline
      monotherapy, no viable organisms could be demonstrated by mouse foot pad
      inoculation and palmitic acid oxidation assays; assays for PGL-I antigen were all
      negative.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730724
TI  - Mycobacterium leprae iron nutrition: bacterioferritin, mycobactin, exochelin and
      intracellular growth.

PMID- 7730725
TI  - "Flu" syndrome due to rifampin; experience with four cases.

PMID- 7730726
TI  - Changes in leprosy clinical pattern after multidrug therapy implementation.

PMID- 7730727
TI  - Acid-fast bacilli from former leprosy regions in coastal Norway showing PCR
      positivity for Mycobacterium leprae.

PMID- 7730728
TI  - Hyperlipidemic treatment changes on the Medicaid formulary.

PMID- 7730729
TI  - Physicians' media image and Medicaid.

PMID- 7730730
TI  - Use of magnetic resonance imaging in central nervous system tumors.
AB  - MRI provides additional information about tumor location, extent, and margins.
      MRI was used in 158 patients with CNS tumors for treatment planning from 1985-89
      and they were studied in a prospective manner. The most common site was cerebrum
      (73 pts), then extradural spinal axis (21 pts) posterior fossa (17 pts), brain
      stem (14 pts) and pituitary (13 pts), etc. The most common histological primary
      tumor was glioblastoma multiform (25 pts), then low grade astrocytoma (22 pts),
      anaplastic astrocytoma (14 pts), pituitary tumor (13 pts), medulloblastoma (9
      pts), ependymoma (7 pts), and germ cell tumors (6 pts). Twenty-nine patients had
      metastasis to the brain. A majority of the patients with CNS tumors had the
      studies using Gadolinium-DTPA. Of the patients with CNS tumors, 120 (76%) had
      better information based on the MRI, which improved the treatment planning (using
      the three dimensional images) and field arrangement. In 89 patients (56%) the MRI
      was very decisive in the treatment volume and field arrangement. In 31 patients
      (20%) the MRI was beneficial and confirmed the treatment plan. MRI provides
      important additional information for radiation therapy planning.

PMID- 7730731
TI  - Polymyositis associated with primary biliary cirrhosis.

PMID- 7730732
TI  - Transjugular Intrahepatic Portosystemic Stent Shunt: nonsurgical therapy for
      portal hypertension.
AB  - The Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) is a new,
      nonsurgical method of lowering portal venous pressure. The procedure is discussed
      and described, and two cases are presented.

PMID- 7730733
TI  - An eight year experience with upper gastrointestinal bleeding: diagnosis,
      treatment and prognosis.
AB  - Bleeding from the upper gastrointestinal tract is one of the most common medical
      emergencies. Admission of patients to a specialized care unit may reduce
      morbidity and mortality. All patients admitted to the Tel Aviv Medical Center,
      between January 1, 1983 and December 31, 1990 with acute upper gastrointestinal
      bleeding, or those who bled while in the hospital, were seen and assessed by a
      senior member of the gastrointestinal service. Endoscopy was performed within 24
      hr of admission. A total of 1110 endoscopies were performed. Duodenal ulcer was
      the main source of bleeding (40.0%). Injection of a vasoconstrictor was used for
      very small blood vessels. Thermal methods were used for small or medium sized
      vessels, or for oozing from a margin ulcer; both with equal rates of success. 153
      (13.8%) surgical procedures were performed. Three (0.37) patients had endoscopic
      cardiovascular complications; one of them died. The in-hospital mortality was
      5.9%. Increasing age, other medical problems, rebleeding and an admission
      hemoglobin of 8 g/dL or less, were associated with increased mortality. Our
      policy of early clinical and endoscopic assessment, and rapid surgical
      intervention in those at high risk, markedly improved survival.

PMID- 7730734
TI  - Time- and frequency-domain analyses of signal-averaged electrocardiograms in
      patients with diabetes mellitus.
AB  - We recorded the signal-averaged electrocardiography (SAECG) of patients with
      diabetic retinopathy in order to clarify whether a ventricular conduction
      disturbance can be detected by time- or frequency-domain analysis of the SAECG.
      Twenty-four normal subjects (N group) and 20 patients with diabetic retinopathy
      [diabetes mellitus (DM) group] were studied. On time-domain analysis, the
      duration of the filtered QRS (f-QRS), the duration of the terminal QRS below 40
      microV (LAS40) and the root-mean-square amplitude of the terminal 40 msec (RMS40)
      were measured. The frequency-domain analysis was performed using two windows. In
      each window, the ratio of the area under the spectral curve from 40 to 100 Hz was
      compared with that from 0 to 40 Hz and the area from 20 to 50 Hz was compared
      with that from 0 to 20 Hz. The LAS40 of the DM group was significantly prolonged
      when compared with the N group. The area ratio from 40 to 100 Hz versus 0 to 40
      Hz significantly increased in the DM group when compared with the N group. These
      results suggest that SAECG can be used to detect abnormal electrical signals due
      to diabetic microangiopathy. Moreover, high frequency components of 40 to 100 Hz
      at the terminus of the QRS wave were most sensitive for abnormalities due to
      diabetic microangiopathy.

PMID- 7730735
TI  - LSA--a new liver-specific antigen in the rat. II: Immunological and biological
      properties.
AB  - The immunological and biological properties of a liver-specific antigen (LSA)
      from rat liver are described. LSA gave interspecies cross-reactions with liver
      extracts from several mammalian species, but no reaction of complete identify was
      observed. Moreover, no cross-reaction was found with chicken or frog livers, thus
      indicating the rather late appearance of LSA in the process of evolution.
      Experiments with fetal and neonatal liver extracts have indicated that LSA
      appears late in fetal development and is always present at birth. The biological
      properties of LSA were explored by several independent approaches. LSAg-Ab
      immunoprecipitates were stained positively with carbon naphthoxycholine iodide,
      an indirect evidence of choline esterase activity. LSA was also found to bind
      bile acids, thus suggesting organic anion properties. Finally, LSA was detected
      in the circulation of rats with acute carbon tetrachloride- and galactosamine
      induced hepatocellular injury. This LSA is immunologically distinct from
      hepatitis B antigen, alpha-fetoprotein, carcino-embryonic antigen and, from each
      of several serum and liver proteins tested.

PMID- 7730736
TI  - Clinical evaluation of the Endosearch sampler in endometrial cytology-a
      preliminary report.
AB  - The clinical value of the Endosearch endometrial cell sampling device was
      assessed in 94 cases managed in our outpatient clinic. The Endosearch could be
      easily inserted into the uterine cavity in 91 (96.8%) of 94 cases without
      analgesia. Pain and prolonged bleeding accompanied by the insertion of the
      Endosearch occurred in eight (8.8%) and six (6.6%) of 91 cases, respectively.
      Satisfactory material for cytologic diagnosis of the endometrial state was
      obtained in 90(98.9%) of 91 cases, which were comparable to those with the
      Endocyte. On the other hand, the endometrial tissue samples could be
      simultaneously obtained with the Endosearch in 78 (85.7%) of 91 cases, and
      histologic diagnosis was possible in 69(88.5%) of 78 cases. Among them, three of
      five cases with endometrial hyperplasia and four of five cases with endometrial
      carcinoma could be correctly diagnosed by the Endosearch histologically. These
      results suggest that outpatient investigation of the endometrial state by the
      Endosearch sampler is quite useful not only in cytologic diagnosis but also in
      histologic evaluation of endometrial lesions.

PMID- 7730737
TI  - Efficacy and short-term effects of pravastatin, a potent inhibitor of HMG-Co A
      reductase, on hypercholesterolemia in climacteric women.
AB  - The effects of pravastatin, a potent inhibitor of HMG-CoA reductase, on serum
      lipids and lipoproteins were studied in 86 patients (36 premenopausal and 50
      postmenopausal women) suffering from primary hypercholesterolemia. The effects of
      this lipid-lowering drug on serum gonadotropins and sex steroids are also
      reported. Pravastatin produced a mean reduction in serum total cholesterol (T
      CHO) of 24.7%, triglyceride (TG) of 30.0%, and low-density lipoprotein
      cholesterol (LDL-CHO) of 36.0% after treatment for three months. The drug also
      produced a mean increase in high-density lipoprotein cholesterol (HDL-CHO) of
      1.4% after three months. Serum follicle-stimulating hormone (FSH), luteinizing
      hormone (LH), estrone (E1), estradiol (E2), and testosterone (T) levels were not
      significantly changed from pre-therapy levels in either pre- or post-menopausal
      women after treatment for six months. Pravastatin is well-tolerated for six
      months and is a very effective lipid lowering agent with no effects on the
      biosynthesis of sex steroids. These findings suggest that pravastatin can be used
      for treatment of primary hypercholesterolemia in women around menopause.

PMID- 7730738
TI  - Dependence on very hot hot-spring bathing in a refractory case of atopic
      dermatitis.
AB  - A 21-year-old female with atopic dermatitis showed "dependence" on very hot hot
      spring bathing. Her skin disease had been refractory to various treatments
      including steroid therapy for a long time. Without medical supervision she took
      four 3-minute 47 degrees C hot-spring baths daily for a month for the purpose of
      improving her skin symptom. Subsequently, she could not stop bathing in very hot
      hot-spring water of her own will. However, a month's isolation in a hospital
      relieved her of the situation. The mechanism of the dependence on very hot hot
      spring bathing may be explained by a transient rise in the plasma beta-endorphin
      level due to hyperthermal stress.

PMID- 7730739
TI  - Suppressed natural killer cell activity in ulcerative colitis.
AB  - We describe a 31-year-old patient with ulcerative colitis who was successfully
      treated with prednisolone (PSL). Immunologic analyses were performed during the
      treatment course. Suppressed natural killer (NK) cell activity and increased
      levels of the CD4/CD8 ratio were observed on admission. Transient restoration of
      NK cell activity was obtained by PSL treatment. However, it returned to the
      initial low level in spite of the improvement of clinical symptoms. Possible
      mechanisms are discussed for involvement of the immune system in the pathogenesis
      of ulcerative colitis (UC).

PMID- 7730740
TI  - More on medical savings accounts.

PMID- 7730741
TI  - They'll take the cash.

PMID- 7730742
TI  - On the ethics of managed competition.

PMID- 7730743
TI  - Ethical values in health care in 1995: lessons from the Nazi period.

PMID- 7730744
TI  - Why managed care won't last.

PMID- 7730745
TI  - Managed health care--patient protection or abuse?

PMID- 7730746
TI  - Managed care: threat or opportunity?

PMID- 7730747
TI  - Medical ethics and managed care.

PMID- 7730748
TI  - Pace of managed care leaves patient safeguards behind.

PMID- 7730749
TI  - 14th Joint meeting of the British Endocrine Societies jointly with the European
      Federation of Endocrine Societies. Warwick, 27-30 March 1995. Abstracts.

PMID- 7730750
TI  - The force-velocity relationship of the ATP-dependent actin-myosin sliding causing
      cytoplasmic streaming in algal cells, studied using a centrifuge microscope.
AB  - When uncoated polystyrene beads suspended in Mg-ATP solution were introduced into
      the internodal cell of an alga Chara corallina, the beads moved along the actin
      cables with directions and velocities (30-62 microns s-1) similar to those of
      native cytoplasmic streaming. Bead movement was inhibited both in the absence of
      ATP and in the presence of CA2+, as with native cytoplasmic streaming. These
      results indicate that bead movement is caused by cytoplasmic myosin molecules
      attached to the head surface interacting with actin cables. The steady-state
      force-velocity relationship of the actin-myosin sliding that produces cytoplasmic
      streaming was determined by applying constant centrifugal forces to the beads
      moving on the actin cables. The force-velocity curve in the positive load region
      was nearly straight, and the implications of this shape are discussed in
      connection with the kinetic properties of the actin-myosin interaction in
      cytoplasmic streaming. It is suggested that the time for which a cytoplasmic
      myosin head is detached from actin in one cycle of actin-myosin interaction is
      very short. The Ca(2+)-induced actin-myosin linkages, responsible for the Ca(2+)
      induced stoppage of cytoplasmic streaming, were shown to be much stronger than
      the rigor actin-myosin linkages.

PMID- 7730751
TI  - The effect of cycle frequency on the power output of rat papillary muscles in
      vitro.
AB  - Papillary muscles were isolated from the right ventricles of rats and the length
      for maximum active force generation (Lmax) was determined isometrically. The work
      loop technique was used to derive the length for maximum work production (Lopt)
      at the cycle frequency, strain amplitude and stimulation phase shift found to be
      optimal for power output. Lopt was typically 7% shorter than Lmax and within the
      physiological length range (87.5% Lmax to Lmax). Net work and power output were
      measured during sinusoidal strain cycles around Lopt, over the cycle frequency
      range 1-9 Hz, strain amplitude and phase shift being optimised for work and power
      at each frequency. Experiments were performed at 37 degrees C. Distinct optima
      were found in both the work-frequency and the power-frequency relationships. The
      optimum cycle frequency for net work production was lower than the frequency for
      maximum power output. The mean maximum power output at 37 degrees C was 8.62 +/-
      0.50 W kg-1 (mean +/- S.E.M., N = 9) and was achieved at a cycle frequency of
      approximately 6 Hz, close to the estimated resting heart rate of 5.8 Hz for the
      rats used (mean mass 223 +/- 25 g). The cycle frequency, strain amplitude and
      stimulation phase shift found to be optimal for power output produced an in vitro
      contraction closely simulating the basal in vivo contraction.

PMID- 7730752
TI  - Serotonergic modulation of swimming speed in the pteropod mollusc Clione
      limacina. I. Serotonin immunoreactivity in the central nervous system and wings.
AB  - Serotonin-immunoreactive somata in the pteropod mollusc Clione limacina were
      restricted to the cerebral and pedal ganglia. 10-14 pairs of cells were
      consistently found in the cerebral ganglia, including one large pair that had
      soma positions and axon branching patterns reminiscent of those of the
      metacerebral cells of other molluscs. Two clusters of somata were found on the
      midline near the cerebral commissure, one on the anterior-lateral margin and one
      posterior-laterally. A distinct paired cluster of up to nine somata was found on
      the dorso-lateral margin of the pedal ganglia, near the emergence of the pedal
      commissure. Up to five of these cells innervated the ipsilateral wing via the
      wing nerve. Dye-fills of these cells showed that they branch repeatedly in the
      ipsilateral wing and innervate the swim musculature. Double-labelling experiments
      indicated that the filled neurons were also serotonin-immunoreactive. Neurobiotin
      fills that were processed for electron microscopy revealed two types of terminals
      associated with the swim musculature: direct contacts and reactive terminals
      adjacent to non-labelled presynaptic terminals. Additional immunoreactive neurons
      in the pedal ganglia included the asymmetrical heart excitor neuron of the left
      pedal ganglion and up to nine ventral somata.

PMID- 7730753
TI  - Serotonergic modulation of swimming speed in the pteropod mollusc Clione
      limacina. II. Peripheral modulatory neurons.
AB  - A symmetrical cluster of serotonin-immunoreactive neurons in the pedal ganglia of
      Clione limacina has been described morphologically and physiologically. At least
      five of the cluster neurons send axons to the ipsilateral wing that branch
      throughout the entire wing area. Activation of these cells did not produce a
      motor effect in non-swimming preparations, but did enhance contractility in
      swimming preparations. Activity in the pedal neurons did not produce detectable
      central effects as neither swim interneuron nor swim motor neuron activities were
      altered. Most notable was a lack of a change in swim frequency, a characteristic
      of swim acceleration. Activity in the pedal neurons did enhance the size of
      muscle junctional potentials and spike-like responses, but only in slow-twitch
      muscles. The peripheral modulatory effect was blocked by the serotonin antagonist
      mianserin.

PMID- 7730754
TI  - Serotonergic modulation of swimming speed in the pteropod mollusc Clione
      limacina. III. Cerebral neurons.
AB  - Swim acceleration in Clione limacina can occur via central inputs to pattern
      generator interneurons and motor neurons and through peripheral inputs to the
      swim musculature. In the previous paper, peripheral modulation of the swim
      muscles was shown to increase wing contractility. In the present paper, central
      inputs are described that trigger an increase in swim frequency and an increase
      in motor neuron activity. In dissected preparations, spontaneous acceleration
      from slow to fast swimming included an increase in the cycle frequency, a
      baseline depolarization in the swim interneurons and an increase in the intensity
      of motoneuron firing. Similar effects could be elicited by bath application of
      10(-5) mol l-1 serotonin. Two clusters of cerebral serotonin-immunoreactive
      interneurons were found to produce acceleration of swimming accompanied by
      changes in neuronal activity. Posterior cluster neurons triggered an increase in
      swim frequency, depolarization of the swim interneurons, an increase in general
      excitor motoneuron activity and activation of type 12 interneurons and pedal
      peripheral modulatory neurons. Cells from the anterior cerebral cluster also
      increased swim frequency, increased activity in the swim motoneurons and
      activated type 12 interneurons, pedal peripheral modulatory neurons and the heart
      excitor neuron. The time course of action of the anterior cluster neurons did not
      greatly outlast the duration of spike activity, while that of the posterior
      cluster neurons typically outlasted burst duration. It appears that the two
      discrete clusters of serotonin-immunoreactive neurons have similar, but not
      identical, effects on swim neurons, raising the possibility that the two
      serotonergic cell groups modulate the same target cells through different
      cellular mechanisms.

PMID- 7730755
TI  - Parasympathetic influence on heart rate in euthermic and hibernating ground
      squirrels.
AB  - The relative role of the parasympathetic nervous system during deep hibernation
      is enigmatic. Conflicting hypotheses exist, and both sides draw support from
      investigations of vagal influence on the heart. Recent studies have shown cardiac
      chronotropic and inotropic effects of parasympathetic stimulation and inhibition
      in isolated hearts and anesthetized animals at hibernating body temperatures. No
      studies, however, have demonstrated such occurrences in undisturbed deeply
      hibernating animals. The present study documents respiratory-related alterations
      in heart rate during euthermia and hibernation at ambient temperatures of 15, 10
      and 5 degrees C mediated by parasympathetic influence. During quiet wakefulness,
      euthermic squirrels breathed continuously and exhibited a 29% acceleration in
      heart rate during inspiration. During deep undisturbed hibernation, at 15, 10 and
      5 degrees C ambient temperature, animals exhibited an episodic breathing pattern
      and body temperatures were slightly above ambient temperature. At each
      temperature, heart rate during the respiratory episode was greater than that
      during the apnea. The magnitude of this ventilatory tachycardia decreased with
      ambient temperature, being 108% at 15 degrees C, 32% at 10 degrees C and 11.5% at
      5 degrees C. Animals exposed to 3% CO2 at 5 degrees C, which significantly
      increased ventilation, still exhibited an 11.7% increase in heart rate during
      breathing. Thus, the magnitude of the ventilation tachycardia was independent of
      the level of ventilation, at least over the range studied. Inhibition of vagus
      nerve conduction at 5 degrees C was achieved using localized nerve block. This
      led to an increase in apneic heart rate and abolished the ventilatory
      tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730756
TI  - Atmospheric controls on elephant communication.
AB  - Atmospheric conditions conducive to long-range transmission of low-frequency
      sound as used by elephants are found to exist in the Etosha National Park in
      Namibia during the late dry season. Meteorological measurements show that strong
      temperature inversions form at the surface before sunset and decay with sunrise,
      often accompanied by calm wind conditions during the early evening. These
      observations are used in an acoustic model to determine the sensitivity of
      infrasound to the effects of (a) the strength, thickness and elevation of
      temperature inversions, and (b) the growth and decay of an inversion typical of
      dry, elevated African savannas. The results suggest that the range over which
      elephants communicate more than doubles at night. Optimum conditions occur 1-2 h
      after sunset on clear, relatively cold, calm nights. At these times, ranges of
      over 10 km are likely, with the greatest amplification occurring at the lowest
      frequency tested. This strong diurnal cycle in communication range may be
      reflected in longer-lasting changes in weather and may exert a significant
      influence on elephant behaviour on time scales from days to many years.

PMID- 7730757
TI  - Functional characterization of leucine transport induced in Xenopus laevis
      oocytes injected with mRNA isolated from midguts of lepidopteran larvae
      (Philosamia cynthia).
AB  - The injection of poly(A)+ mRNA prepared from Philosamia cynthia midgut caused
      time- and dose-dependent increases of leucine transport in Xenopus laevis
      oocytes, with an increase in leucine uptake 1.5-3 times that of oocytes injected
      with water. When the NaCl concentration was reduced from 100 to 5 mmol l-1, the
      difference between mRNA- and water-injected oocytes was greater and a fourfold
      increase of L-leucine uptake was measured. D-Leucine (10 mmol l-1) completely
      inhibited the induced uptake of 0.1 mmol l-1 L-leucine. The newly expressed
      component of L-leucine uptake increased at alkaline pH and was abolished by
      incubation for 15 min with 15 mmol l-1 phenylglyoxal. The mean Km values,
      calculated using Na+ activation curves of leucine uptake, were 23.3 +/- 6.1 mmol
      l-1 in water-injected oocytes and 0.4 +/- 0.2 mmol l-1 for the newly expressed
      component of leucine uptake in mRNA-injected oocytes. On the basis of these
      results, we conclude that the increase of L-leucine uptake in mRNA-injected
      oocytes was due to the expression of a new transport system, which differs from
      the endogenous ones and shares many features with that found previously in
      Philosamia cynthia midgut.

PMID- 7730758
TI  - Active calcium transport in the skin of the frog Rana pipiens: kinetics and
      seasonal rhythms.
AB  - The frog Rana pipiens takes up Ca2+ against an electrochemical gradient from
      dilute external solutions that are similar to natural freshwater environments.
      The influx is dependent upon external [Ca2+] and is saturable. Kinetic analysis
      yielded a Km of 0.625 mmol l-1 and a Jmax of 38 nmol cm-2h-1. These kinetic
      variables suggest that both the affinity and capacity are smaller than those for
      Na+ and Cl- transport in the skin of the same species. They are also smaller than
      those for Ca2+ transport in fish gill. A significant portion (20-25%) of the Ca2+
      entering a frog remains in Ca(2+)-rich layers of the skin, with ventral skin
      containing about three times as much Ca2+ as dorsal skin. There are seasonal
      rhythms in Ca2+ exchange: although Ca2+ influx does not vary significantly over
      the year, efflux is minimal in July, while net flux, which is negative most of
      the year, appears to be positive in July. Since these fluxes do not include
      dietary calcium, one cannot conclude that feeding frogs are in negative Ca2+
      balance.

PMID- 7730759
TI  - The EMG-force relationship of the cat soleus muscle and its association with
      contractile conditions during locomotion.
AB  - The relationship between force and electromyographic (EMG) signals of the cat
      soleus muscle was obtained for three animals during locomotion at five different
      speeds (154 steps), using implanted EMG electrodes and a force transducer.
      Experimentally obtained force-IEMG (= integrated EMG) relationships were compared
      with theoretically predicted instantaneous activation levels calculated by
      dividing the measured force by the predicted maximal force that the muscle could
      possibly generate as a function of its instantaneous contractile conditions. In
      addition, muscular forces were estimated from the corresponding EMG records
      exclusively using an adaptive filtering approach. Mean force-IEMG relationships
      were highly non-linear but similar in shape for different cats and different
      speeds of locomotion. The theoretically predicted activation-time plots typically
      showed two peaks, as did the IEMG-time plots. The first IEMG peak tended to be
      higher than the second one and it appeared to be associated with the initial
      priming of the muscle for force production at paw contact and the peak force
      observed early during the stance phase. The second IEMG peak appeared to be a
      burst of high muscle activation, which might have compensated for the levels of
      muscle length and shortening velocity that were suboptimal during the latter part
      of the stance phase. Although it was difficult to explain the soleus forces on
      the basis of the theoretically predicted instantaneous activation levels, it was
      straightforward to approximate these forces accurately from EMG data using an
      adaptive filtering approach.

PMID- 7730760
TI  - Locomotor behavior of nocturnal ghost crabs on the beach: focal animal sampling
      and instantaneous velocity from three-dimensional motion analysis.
AB  - Previous laboratory measurements of the energetics and biomechanics of locomotion
      have defined performance limits for the ghost crab Ocypode quadrata. To discover
      whether these animals naturally operate within these limits, a novel infrared
      videotaping system was used to observe nocturnally active ghost crabs in the
      field for three-dimensional motion analysis (N = 27) and focal animal sampling (N
      = 24). Instantaneous movement velocity, movement duration, pause duration and
      stride frequency were determined from video tapes. Voluntarily active crabs moved
      at a mean instantaneous velocity of 8 cm s-1. Stressed crabs (i.e. those captured
      and released into the field site) moved at a mean velocity of 83 cm s-1. The mean
      movement and pause period durations of voluntarily active animals moving along
      the beach were 11.2 and 23.4 s, respectively. Stressed crabs had much shorter
      movement (1.4 s) and pause (7.6 s) durations. Despite the differences in mean
      movement and pause duration, both voluntarily active and stressed crabs moved for
      an average of approximately 30% of the observation period. These data indicate
      that voluntarily active ghost crabs primarily move at velocities that can be
      sustained aerobically and that their performance is not likely to be altered by
      moving intermittently. By contrast, stressed crabs move at faster speeds that are
      closer to the limits of their continuous locomotor performance (e.g. escape
      behavior and aggressive encounters). In the laboratory, the endurance capacity of
      crabs moving continuously at these rapid speeds is only a few seconds. However,
      in the field, the stressed crabs are able to move intermittently for more than a
      few seconds, yet they do not fatigue. These observations suggest that the
      performance limits of the stressed crabs are increased by moving intermittently.

PMID- 7730761
TI  - More pearls.

PMID- 7730762
TI  - More pearls.

PMID- 7730763
TI  - More pearls.

PMID- 7730764
TI  - More pearls.

PMID- 7730765
TI  - More pearls.

PMID- 7730766
TI  - Development and implementation of guidelines for family practice: lessons from
      The Netherlands.

PMID- 7730767
TI  - Morbidity, mortality, and charges for hospital care of the elderly: a comparison
      of internists' and family physicians' admissions.
AB  - BACKGROUND: In an atmosphere of cost containment, an important question is
      whether there are differences in quality or cost of medical care provided by
      physicians with different specialty training. METHODS: This study is an analysis
      of Pennsylvania hospital admissions from the 1989 MedisGroups Comparative
      Database, consisting of 31,321 hospital admissions by internists and family
      physicians. It encompasses the top 10 admission diagnostic-related groups in
      patients 65 years and older. Outcome measures of morbidity, mortality, length of
      stay, and hospital charges were compared between patients of internists and
      family physicians while controlling for patient variables, such as age, sex,
      Medicaid insurance payment, admission from nursing home, and admission severity
      scores, and hospital characteristics, such as number of beds, teaching status,
      and available technologies and procedures. RESULTS: Admission diagnoses were
      similar for patients of family physicians and internists. After adjusting for
      relevant patient and hospital characteristics, there were no differences in
      mortality or hospital charges; however, the patients of internists experienced
      slightly higher morbidity (odds ratio = 1.07, 95% confidence interval, 1.017 to
      1.123) and longer mean length of stay (10.80 vs 10.54 days, P < .05). The mean
      age of patients and the proportion of Medicaid patients was similar in the two
      specialty groups. Family physicians' patients were more likely to be female (60%
      vs 57%, P < .01), were less likely to be admitted from nursing homes (4% vs 5%, P
      < .01), and had a lower mean admission severity score (1.940 vs 1.964 on a scale
      of 0 [least seriously ill] to 4 [most seriously ill], P < .01). Internists were
      more likely to work in teaching hospitals and hospitals with sophisticated
      technology (P < .01). CONCLUSIONS: It makes little difference in medical outcomes
      or hospital charges whether family physicians or internists manage the hospital
      care of elderly patients for common medical problems. Previously documented lower
      costs of care by family physicians may be due to outpatient rather than inpatient
      care.

PMID- 7730768
TI  - Cost of care for ambulatory patients with low back pain.
AB  - BACKGROUND: Low back pain is a common presenting complaint in primary care, and
      the rate of utilization of resources among physicians treating this condition
      varies. Charges associated with the care of patients with low back pain were
      analyzed for a series of patients in a multispecialty group practice setting.
      METHODS: One hundred seventy managed care patients were selected for review. Use
      of laboratory, plain radiography, magnetic resonance imaging (MRI), subspecialty
      referrals, and physical therapy was examined based on patient characteristics and
      physician specialty. Appropriateness of MRI and lumbar spine radiography
      according to published criteria was also studied. RESULTS: Overall utilization
      was higher for patients who were referred to a subspecialist, and costs for
      visits to subspecialists were higher. Charges for physician services and MRI
      accounted for a majority of the total charges. Patients who were referred for
      subspecialty care or MRI but did not meet criteria for utilization of these
      resources comprised 6% of the study population but accounted for 27% of the total
      charges. Five of 14 patients undergoing MRI did not meet the published clinical
      criteria determining need for MRI, and 10 of 17 patients referred to
      subspecialists did not meet referral criteria. Other patients who met criteria
      for MRI or subspecialty consultation did not receive these services. Seventeen
      percent of the patients referred for physical therapy had a symptom duration of 2
      weeks or less at the time of referral and accounted for 17% of all physical
      therapy charges. CONCLUSIONS: The majority of costs associated with care for low
      back pain in this study were attributable to physician charges and the use of
      MRI. Charges for subspecialty physician services, lumbar spine radiographs, and
      MRI in patients not meeting appropriate criteria accounted for 19% of all costs.

PMID- 7730769
TI  - Obstetrical practice among new rural family physicians.
AB  - BACKGROUND: Fewer family physicians now practice maternity care than a decade
      ago, a trend that is worsening access to obstetrical care in some rural areas.
      This study explores the effects of a wide range of factors on the likelihood of
      newly settled rural family physicians providing maternity care. METHODS: Subjects
      included 782 family physicians who moved to nonmetropolitan areas nationwide
      during the years 1987 through 1990. Physicians who located in health professional
      shortage areas were oversampled. Questionnaires were mailed in 1991, with a 72%
      response rate. The final sample used in the analyses included 338 eligible
      respondents. RESULTS: A total of 151 (45%) of these rural family physicians
      performed routine deliveries during the previous year. Family physicians more
      likely to provide maternity care worked in practices they owned and were not solo
      practitioners (P < or = .05). Maternity care by family physicians also was more
      common in counties that were less populated, had fewer obstetricians, and had
      more family physicians. State-by-state differences in the cost of medical
      malpractice insurance and Medicaid reimbursement rates for obstetrical care were
      not among the factors associated with the provision of maternity care for these
      rural family physicians. CONCLUSIONS: These data suggest that features of rural
      family physicians' practices and communities are the best predictors of whether
      they provide maternity care. Contrary to what family physicians often claim, we
      found that malpractice premium costs and Medicaid reimbursement rates were not
      associated with family physicians' likelihood of providing maternity care.

PMID- 7730770
TI  - A qualitative study of the perceptions of dissatisfied Norplant users.
AB  - BACKGROUND: The purpose of this study was to examine specific factors that
      motivated the request for early removal of Norplant among a group of young, low
      income women who were dissatisfied with this contraceptive method. METHODS: Focus
      groups were conducted to obtain qualitative in-depth attitude and opinion data
      about Norplant from women who had used this method of contraception for a period
      ranging from 2 months to 25 months and had requested its removal because of side
      effects. RESULTS: Patient motivation for requesting Norplant removal was based on
      side effects. No other reason for early removal requests emerged from the focus
      group discussions. However, the comments of many participants raised questions
      about the psychosocial context in which patients obtain information about
      Norplant and request early removal. Many participants mentioned having felt
      pressured to accept Norplant and not being fully informed about possible side
      effects. All but two said they were encouraged to "wait out" side effects and
      that physicians were reluctant to remove the Norplant capsules. Many participants
      recalled that they had to request removal several times before their physicians
      complied with their wishes. CONCLUSIONS: The results of this study suggest that
      there is a need to review the process of educating patients about Norplant, the
      situational context of Norplant counseling, and physician practices related to
      patients' requests for early removal.

PMID- 7730771
TI  - Skin-cancer screening: a three-year experience that paid for itself.
AB  - BACKGROUND: The incidence of cutaneous malignant melanoma is steadily rising.
      Although cancer screening guidelines seek to increase the frequency of curative
      early excision of melanomas, it is unclear how these guidelines can be
      economically incorporated into clinical practice. METHODS: A free skin-cancer
      screening clinic, which used a brief undressed skin examination, was held
      annually for 3 successive years at a private, rural, family physician's office.
      The goal was to identify undiagnosed melanomas with the expectation of finding
      other skin cancers as well. Data were collected on marginal costs to the
      practice, confirmatory follow-up examinations, and marginal revenue received from
      follow-up treatment with the author. RESULTS: Of 247 persons screened, 70 (28%)
      sought a follow-up examination with either the author (38 patients) or their
      primary or other consulting physicians (32 patients). Fifty-four percent of the
      70 patients who followed up (15% of the total screened) were found on biopsy or
      repeat physical examination to have malignant or premalignant lesions, including
      one melanoma. The 38 participants seen in follow-up by the author generated 114
      patient encounters with the billing of 151 procedures and office visits. Marginal
      revenues generated by the follow-up procedures and office visits with the author
      following this free skin-cancer screening exceeded by 3.6 times the marginal cost
      of the screening. CONCLUSIONS: A free mass skin-cancer screening in a rural
      setting by a family physician can identify melanoma and other previously
      undiagnosed skin cancers and pay for itself as well.

PMID- 7730772
TI  - A novel method for isolating and quantifying urine pathogens collected from gel
      based diapers.
AB  - BACKGROUND: Given that children often present to physicians with a wet gel-based
      diaper, a method for using this diaper for a urine specimen was studied. METHODS:
      A blinded clinical laboratory trial was conducted in the microbiology laboratory.
      The sampling technique involved the use of oval gynecologic forceps as a template
      and sterile scissors to cut out samples of diapers. Each diaper sample was then
      vortexed in 20 mL of sterile saline and the supernatant quantitatively cultured.
      Diaper sample supernatant cultures with simulated infected urines (suspensions of
      Escherichia coli) were used. RESULTS: Weight measurements of the diaper samples
      soaked with 20 mL or more of saline yielded reproducible results (0.703 g; 95%
      confidence interval [CI], 0.52 to 0.88 g). Culture results (colony-forming units
      per liter [CFU/L] of supernatant) from diapers soaked with 25 mL of various
      concentrations of E coli (10(6), 10(7), 10(8), 10(9) CFU/L) showed excellent
      correlation with the inoculum used, and no effect of a 2-hour delay in culturing
      the wet diapers. CONCLUSIONS: Our technique provides accurate and reliable
      estimates of bacterial concentrations in the usual range for infected urine from
      gel-based diapers soaked with solutions of E coli. Further evaluation of clinical
      implementation is needed.

PMID- 7730773
TI  - Neoplasm as a cause of shoulder pain.
AB  - For most patients with shoulder pain, complaints are related to impingement
      syndrome, degenerative or inflammatory joint disease, instability, or trauma.
      Neoplasm is a rare cause of shoulder pain, but should be considered, especially
      when patient presentation is unusual. This review includes a series of cases in
      which tumor was found to be the cause of pain.

PMID- 7730774
TI  - Lesbian health issues for the primary care provider.
AB  - Lesbians have unique health concerns that often go unaddressed in a medical
      setting that assumes heterosexuality. These may include cancer screening,
      sexually transmitted diseases, human immunodeficiency virus (HIV), depression,
      substance abuse, relationship issues, pregnancy, and parenting. Awareness of the
      barriers faced by lesbians seeking care, and an inclusive approach to the patient
      will allow primary care providers to be more effective in their interactions with
      all patients.

PMID- 7730775
TI  - Acute cerebellar ataxia associated with varicella.

PMID- 7730776
TI  - Minocycline for rheumatoid arthritis.

PMID- 7730777
TI  - Simvastatin decreases mortality.

PMID- 7730778
TI  - Effect of epidural anesthesia on labor.

PMID- 7730779
TI  - More pearls.

PMID- 7730780
TI  - More pearls.

PMID- 7730781
TI  - The "family" in family medicine.

PMID- 7730782
TI  - The "family" in family medicine.

PMID- 7730783
TI  - The "family" in family medicine.

PMID- 7730784
TI  - Pseudoephedrine and blood pressure.

PMID- 7730785
TI  - Halting hiccups.

PMID- 7730786
TI  - Urinalysis predictive of UTI.

PMID- 7730787
TI  - The relationship between contractile force and intracellular [Ca2+] in intact rat
      cardiac trabeculae.
AB  - The control of force by [Ca2+] was investigated in rat cardiac trabeculae loaded
      with fura-2 salt. At sarcomere lengths of 2.1-2.3 microns, the steady state force
      [Ca2+]i relationship during tetanization in the presence of ryanodine was half
      maximally activated at a [Ca2+]i of 0.65 +/- 0.19 microM with a Hill coefficient
      of 5.2 +/- 1.2 (mean +/- SD, n = 9), and the maximal stress produced at
      saturating [Ca2+]i equalled 121 +/- 35 mN/mm2 (n = 9). The dependence of steady
      state force on [Ca2+]i was identical in muscles tetanized in the presence of the
      Ca(2+)-ATPase inhibitor cyclopiazonic acid (CPA). The force-[Ca2+]i relationship
      during the relaxation of twitches in the presence of CPA coincided exactly to
      that measured at steady state during tetani, suggesting that CPA slows the decay
      rate of [Ca2+]i sufficiently to allow the force to come into a steady state with
      the [Ca2+]i. In contrast, the relationship of force to [Ca2+]i during the
      relaxation phase of control twitches was shifted leftward relative to the steady
      state relationship, establishing that relaxation is limited by the contractile
      system itself, not by Ca2+ removal from the cytosol. Under control conditions the
      force-[Ca2+]i relationship, quantified at the time of peak twitch force (i.e.,
      dF/dt = 0), coincided fairly well with steady state measurements in some
      trabeculae (i.e., three of seven). However, the force-[Ca2+]i relationship at
      peak force did not correspond to the steady state measurements after the
      application of 5 mM 2,3-butanedione monoxime (BDM) (to accelerate cross-bridge
      kinetics) or 100 microM CPA (to slow the relaxation of the [Ca2+]i transient).
      Therefore, we conclude that the relationship of force to [Ca2+]i during
      physiological twitch contractions cannot be used to predict the steady state
      relationship.

PMID- 7730788
TI  - The lifetime of inositol 1,4,5-trisphosphate in single cells.
AB  - In many eukaryotic cell types, receptor activation leads to the formation of
      inositol 1,4,5-trisphosphate (IP3) which causes calcium ions (Ca) to be released
      from internal stores. Ca release was observed in response to the muscarinic
      agonist carbachol by fura-2 imaging of N1E-115 neuroblastoma cells. Ca release
      followed receptor activation after a latency of 0.4 to 20 s. Latency was not
      caused by Ca feedback on IP3 receptors, but rather by IP3 accumulation to a
      threshold for release. The dependence of latency on carbachol dose was fitted to
      a model in which IP3 synthesis and degradation compete, resulting in gradual
      accumulation to a threshold level at which Ca release becomes regenerative. This
      analysis gave degradation rate constants of IP3 in single cells ranging from 0 to
      0.284 s-1 (0.058 +/- 0.067 s-1 SD, 53 cells) and a mean IP3 lifetime of 9.2 +/-
      2.2 s. IP3 degradation was also measured directly with biochemical methods. This
      gave a half life of 9 +/- 2 s. The rate of IP3 degradation sets the time frame
      over which IP3 accumulations are integrated as input signals. IP3 levels are also
      filtered over time, and on average, large-amplitude oscillations in IP3 in these
      cells cannot occur with period < 10 s.

PMID- 7730789
TI  - The calcium-activated potassium channels of turtle hair cells.
AB  - A major factor determining the electrical resonant frequency of turtle cochlear
      hair cells is the time course of the Ca-activated K current (Art, J. J., and R.
      Fettiplace. 1987. Journal of Physiology. 385:207-242). We have examined the
      notion that this time course is dictated by the K channel kinetics by recording
      single Ca-activated K channels in inside-out patches from isolated cells. A hair
      cell's resonant frequency was estimated from its known correlation with the
      dimensions of the hair bundle. All cells possess BK channels with a similar unit
      conductance of approximately 320 pS but with different mean open times of 0.25-12
      ms. The time constant of relaxation of the average single-channel current at -50
      mV in 4 microM Ca varied between cells from 0.4 to 13 ms and was correlated with
      the hair bundle height. The magnitude and voltage dependence of the time constant
      agree with the expected behavior of the macroscopic K(Ca) current, whose speed
      may thus be limited by the channel kinetics. All BK channels had similar
      sensitivities to Ca which produced half-maximal activation for a concentration of
      approximately 2 microM at +50 mV and 12 microM at -50 mV. We estimate from the
      voltage dependence of the whole-cell K(Ca) current that the BK channels may be
      fully activated at -35 mV by a rise in intracellular Ca to 50 microM. BK channels
      were occasionally observed to switch between slow and fast gating modes which
      raises the possibility that the range of kinetics of BK channels observed in
      different hair cells reflects a common channel protein whose kinetics are
      regulated by an unidentified intracellular factor. Membrane patches also
      contained 30 pS SK channels which were approximately 5 times more Ca-sensitive
      than BK channels at -50 mV. The SK channels may underlie the inhibitory synaptic
      potential produced in hair cells by efferent stimulation.

PMID- 7730790
TI  - Plasticity in canine airway smooth muscle.
AB  - The large volume changes of some hollow viscera require a greater length range
      for the smooth muscle of their walls than can be accommodated by a fixed array of
      sliding filaments. A possible explanation is that smooth muscles adapt to length
      changes by forming variable numbers of contractile units in series. To test for
      such plasticity we examined the muscle length dependence of shortening velocity
      and compliance, both of which will vary directly with the number of thick
      filaments in series. Dog tracheal smooth muscle was studied because its cells are
      arrayed in long, straight, parallel bundles that span the length of the
      preparation. In experiments where muscle length was changed, both compliance and
      velocity showed a strong dependence on muscle length, varying by 1.7-fold and 2.2
      fold, respectively, over a threefold range of length. The variation in isometric
      force was substantially less, ranging from a 1.2- to 1.3-fold in two series of
      experiments where length was varied by twofold to an insignificant 4% variation
      in a third series where a threefold length range was studied. Tetanic force was
      below its steady level after both stretches and releases, and increased to a
      steady level with 5-6 tetani at 5 min intervals. These results suggest strongly
      that the number of contractile units in series varies directly with the adapted
      muscle length. Temporary force depression after a length change would occur if
      the change transiently moved the filaments from their optimum overlap. The
      relative length independence of the adapted force is explained by the reforming
      of the filament lattice to produce optimum force development, with commensurate
      changes of velocity and compliance.

PMID- 7730792
TI  - Prunus necrotic ringspot ilarvirus: nucleotide sequence of RNA3 and the
      relationship to other ilarviruses based on coat protein comparison.
AB  - The RNA3 of prunus necrotic ringspot ilarvirus (PNRSV) has been cloned and its
      entire sequence determined. The RNA3 consists of 1943 nucleotides (nt) and
      possesses two large open reading frames (ORFs) separated by an intergenic region
      of 74 nt. The 5' proximal ORF is 855 nt in length and codes for a protein of
      molecular mass 31.4 kDa which has homologies with the putative movement protein
      of other members of the Bromoviridae. The 3' proximal ORF of 675 nt is the
      cistron for the coat protein (CP) and has a predicted molecular mass of 24.9 kDa.
      The sequence of the 3' non-coding region (NCR) of PNRSV RNA3 showed a high degree
      of similarity with those of tobacco streak virus (TSV), prune dwarf virus (PDV),
      apple mosaic virus (ApMV) and also alfalfa mosaic virus (AIMV). In addition it
      contained potential stem-loop structures with interspersed AUGC motifs
      characteristic for ilar- and alfamoviruses. This conserved primary and secondary
      structure in all 3' NCRs may be responsible for the interaction with homologous
      and heterologous CPs and subsequent activation of genome replication. The CP gene
      of an ApMV isolate (ApMV-G) of 657 nt has also been cloned and sequenced.
      Although ApMV and PNRSV have a distant serological relationship, the deduced
      amino acid sequences of their CPs have an identity of only 51.8%. The N termini
      of PNRSV and ApMV CPs have in common a zinc-finger motif and the potential to
      form an amphipathic helix.

PMID- 7730791
TI  - Measurement of cytosolic Ca2+ concentration in Limulus ventral photoreceptors
      using fluorescent dyes.
AB  - Several Ca-sensitive fluorescent dyes (fura-2, mag-fura-2 and Calcium Green-5N)
      were used to measure intracellular calcium ion concentration, Cai, accompanying
      light-induced excitation of Limulus ventral nerve photoreceptors. A ratiometric
      procedure was developed for quantification of Calcium Green-5N fluorescence. A
      mixture of Calcium Green-5N and a Ca-insensitive dye, ANTS, was injected in the
      cell and the fluorescence intensities of both dyes were used to calculate the
      spatial average of Cai within the light-sensitive R lobe of the photoreceptor. In
      dark-adapted photoreceptors, the initial Cai was 0.40 +/- 0.22 microM (SD, n = 7)
      as measured with fura-2. Cai peaked in the light-sensitive R lobe at 700-900 ms
      after the onset of an intense measuring light step, when the spatial average of
      Cai within the R lobe reached 68 +/- 14 and 62 +/- 37 microM (SD, n = 5) as
      measured with mag-fura-2 and Calcium Green-5N, respectively. The rate of Cai rise
      was calculated to be approximately 350 microM/s under the measuring conditions.
      The resting level of Mg2+ was estimated to be 1.9 +/- 0.9 mM, calculated from mag
      fura-2 measurements. To investigate the effect of adapting light on the initial
      Cai level in the R lobe, a 1-min step of 420 nm background light was applied
      before each measurement. The first significant (P < 0.05) change in the initial
      level of Cai occurred even at the lowest adapting light intensity, which
      delivered approximately 3 x 10(3) effective photons/s. The relative sensitivity
      of the light-adapted photoreceptors was linearly related to the relative Cai on a
      double log plot with slope between -4.3 and -5.3. We were unable to detect a Cai
      rise preceding the light-activated receptor potential. The Cai rise, measured
      with Calcium Green-5N, lagged 14 +/- 5 ms (SD, n = 32) behind the onset of the
      receptor potential at room temperature in normal ASW. In the absence of
      extracellular Ca2+ and at 10 degrees C, this lag increased to 44 +/- 12 ms (SD, n
      = 17).

PMID- 7730793
TI  - Structural sites specific to citrus viroid groups.
AB  - Synthesis of cDNA probes by random-priming of a viroid template displays the
      unusual property of specificity to all members included within a single citrus
      viroid Group. The specificity of hybridization reactions was influenced by the
      structural conformation of the viroid RNA template, reaction conditions for
      reverse transcription and hybridization protocols. Mapping the loci for probe
      transcription from the CEVd, CVd-IIb, and CVd-IV genomes suggests that a similar
      structured conformation may be responsible for group specificity. A stem-loop
      configuration in the viroid template and hybridization target sites can be
      proposed to be responsible for the availability of the group-specific sequences.

PMID- 7730794
TI  - Characterization of v-cath, a cathepsin L-like proteinase expressed by the
      baculovirus Autographa californica multiple nuclear polyhedrosis virus.
AB  - Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) contains a
      966 bp ORF that encodes a papain type cysteine proteinase with cathepsin L-like
      characteristics. Using Western blot analysis of infected cell extracts we showed
      that v-cath proteinase has 35.5 kDa and 32 kDa precursor forms which are
      processed to a 27.5 kDa mature form in a manner characteristic of papain and
      cathepsin L. V-cath proteinase activity was greatest under acidic conditions (pH
      5.0) and was reduced in the presence of the cysteine proteinase inhibitors,
      leupeptin and E64. Urea, a known enhancer of cathepsin L activity, also enhanced
      v-cath proteinase activity. AcMNPV v-cath proteinase was detected post-mortem in
      tissues of insects infected with wild-type (wt) virus. Insects infected with a v
      cath deletion mutant did not become flaccid after death as is normally observed
      with wt AcMNPV infections. These findings indicate a link between v-cath activity
      and degradation of host tissues during virus pathogenesis.

PMID- 7730795
TI  - Identification and properties of the largest subunit of the DNA-dependent RNA
      polymerase of fish lymphocystis disease virus: dramatic difference in the domain
      organization in the family Iridoviridae.
AB  - Cytoplasmic DNA viruses encode a DNA-dependent RNA polymerase (DdRP) that is
      essential for transcription of viral genes. The amino acid sequences of the known
      largest subunits of DdRPs from different species contain highly conserved
      regions. Oligonucleotide primers, deduced from two conserved domains (RQP[T/S]LH
      and NADFDGDE) were used for detecting the corresponding gene of fish lymphocystis
      disease virus (FLCDV), a member of the family Iridoviridae, which replicates in
      the cytoplasm of infected cells of flatfish. The gene coding for the largest
      subunit of the DdRP was identified using a PCR-derived probe. The screening of
      the complete EcoRI gene library of the viral genome led to the identification of
      the gene locus of the largest subunit of the DdRP within the EcoRI DNA fragment B
      (12.4 kbp, 0.034 to 0.165 map units). The nucleotide sequence of a part (8334 bp)
      of the EcoRI DNA fragment B was determined and a large ORF on the lower strand
      (ATG = 5787; TAA = 2190) was detected which encodes a protein of 1199 amino
      acids. Comparison of the amino acid sequences of the largest subunits of the DdRP
      (RPO1) of FLCDV and Chilo iridescent virus (CIV) revealed a dramatic difference
      in their domain organization. Unlike the 1051 aa RPO1 of CIV, which lacks the C
      terminal domain conserved in eukaryotic, eubacterial and other viral RNA
      polymerases, the 1199 aa RPO1 of FLCDV is fully collinear with its cellular and
      viral homologues. Despite this difference, comparative analysis of the amino acid
      sequences of viral and cellular RNA polymerases suggests a common origin for the
      largest RNA polymerase subunits of FLCDV and CIV.

PMID- 7730796
TI  - Identification and characterization of the thymidine kinase gene of Yaba virus.
AB  - DNA of Yaba virus, a member of the poxviruses, was mapped by cross-hybridization
      between fragments of various restriction enzymes. The genome was approximately
      135 kb in length and possessed two characteristic features of poxviruses: cross
      links and inverted terminal repeats at both termini. Hybridization of fragments
      of Yaba virus DNA to known vaccinia virus DNA fragments indicated that the
      thymidine kinase (TK) gene mapped within the 0.9 kb XhoI-HincII fragment between
      52.5 and 53.5 kb from the left end of the genome. The fragment could rescue the
      TK+ phenotype in TK- cells preinfected with a TK vaccinia virus mutant.
      Nucleotide sequencing of the fragment revealed an ORF capable of encoding 181
      amino acids. The sequence TAAAAATGAAAAATTA upstream of the ORF was considered to
      be the promoter and the downstream sequence TTTTTAT to be the early transcription
      termination signal. These sequences are in good accord with the consensus
      regulatory sequences for the expression of early genes of other known poxviruses.
      The amino acid sequence similarity among the poxvirus TK genes suggests that Yaba
      virus is most closely related to swinepox virus and less similar to fowlpox
      virus.

PMID- 7730797
TI  - African swine fever virus gene j13L encodes a 25-27 kDa virion protein with
      variable numbers of amino acid repeats.
AB  - The African swine fever virus (ASFV) j13L gene encodes a 177 amino acid protein
      (19.0 kDa) with a putative transmembrane domain between residues 32 and 52. There
      is a potential signal peptide cleavage site at residue 54 and several possible
      motifs for phosphorylation and myristylation. Rabbit antisera raised against a
      synthetic peptide from the C terminus of the j13L ORF identified proteins of 25
      27 kDa in cells infected with a recombinant vaccinia virus expressing the j13L
      ORF, in ASFV-infected cells and in purified extracellular ASF virions. In ASFV
      infected cells the j13L protein was expressed late during infection and exhibited
      size variation (25-27 kDa) between the different ASFV strains. Nucleotide
      sequence analysis of the gene in these strains showed that these size differences
      were due to variation in the number and sequence of tandemly repeated amino acid
      repeats. Although ASFV-infected animals made antibodies to the j13L protein, no
      protection was observed when pigs were vaccinated with a recombinant vaccinia
      virus expressing the j13L ORF.

PMID- 7730798
TI  - Bovine papillomavirus type 1 E1 ATPase activity does not depend on binding to DNA
      nor to viral E2 protein.
AB  - Replication of bovine papillomavirus type 1 (BPV-1) DNA has been shown to require
      two viral proteins known to interact in a molecular complex: E2, a transcription
      activator, and E1, another nuclear phosphoprotein, which binds to the replication
      origin and for which helicase/ATPase activities have previously been reported.
      Here we characterize the BPV-1 E1 ATPase activity. In contrast to Seo et al.
      (Proceedings of the National Academy of Sciences, USA, 90, 702-706, 1993), we
      were able to detect this activity in the absence of nucleic acid in partially
      purified preparations of either E1 protein or of E1-E2 protein complex.
      Measurements of specific activity and kinetic parameters gave similar values for
      preparations of various kinds. ATPase activity was quantitatively retained by
      immunoprecipitates obtained by using anti-E1 or, in the case of E1-E2 complex,
      anti-E2 antibodies. Significantly, preparations of bacterially expressed
      glutathione S-transferase-E1 fusion protein exhibited levels of DNA-independent
      ATPase activity comparable to those of baculovirus-expressed E1. The presence of
      nucleic acids of various types, including stoichiometric amounts of a BPV-1 ori
      DNA fragment containing E1 and E2 binding sites, did not grossly affect E1 ATPase
      activity, the most notable effect being a 2-fold stimulation by unspecific ssDNA.
      Altogether, our results indicate that BPV-1 E1 possesses an intrinsic ATPase
      activity which does not depend on the presence of nucleic acid; moreover, they
      render unlikely any modulation of E1 ATPase activity due to binding either E2
      protein or target DNA sequences, or as a result of protein phosphorylation.

PMID- 7730799
TI  - CD4 expression on dendritic cells and their infection by human immunodeficiency
      virus.
AB  - Infection of dendritic cells (DC) by human immunodeficiency virus (HIV) has been
      disputed. Employing a fluorescence-activated cell sorter, DC, identified by the
      absence of membrane markers for T, B, natural killer (NK) and monocytic cells and
      by high levels of MHC class II DR antigen, were shown to express low levels of
      CD4. Immunomagnetic beads were used to separate blood low density cells, which
      are enriched for DC, into CD4-positive and -negative populations. Examination of
      these cells by electron microscopy showed an increase in the percentage of cells
      with DC morphology in the CD4-positive fraction and a reduction in the CD4
      negative fraction. Electron microscopy of semi-purified DC preparations infected
      in vitro for 5 days with HIV-1 revealed morphologically distinct veiled DC with
      mature virions on the cell surface and virus budding through the cell membrane.
      Further evidence for the growth of HIV in DC was provided by experiments in which
      DC were extensively depleted of contaminating lymphocytes and monocytes prior to
      infection. Estimation of provirus load by a nested PCR indicated that after 5
      days an infection level of one provirus copy per five cells could be achieved.
      After 7 days the provirus copy number could exceed the cellular genome copy
      number, suggesting that some cells had more than one provirus. Infectious virus
      could not be demonstrated in these cultures after 24 h but was detected after 5
      or 7 days. Infection of DC in the presence of antibodies against CD4 was
      inhibited and suggests infection occurs via a CD4-dependent pathway. These
      results confirm that DC are susceptible to HIV infection in vitro. The
      immunological consequences of DC infection in vivo may be significant in the
      pathogenesis of AIDS.

PMID- 7730800
TI  - Mapping of neutralization epitopes on infectious pancreatic necrosis viruses.
AB  - We have characterized and mapped variable and conserved neutralization epitopes
      of serogroup A strains of aquatic birnaviruses. Epitope mapping using monoclonal
      antibodies (MAbs) and Escherichia coli-expressed deletion fragments of VP2 of the
      N1 strain of infectious pancreatic necrosis virus (IPNV) demonstrated that two
      variable epitopes, H8 and B9, depend on the variable region between amino acid
      204-330. A conserved neutralization epitope, F2, was shown to depend on the same
      region as epitopes H8 and B9 but was additionally dependent on amino acids
      between 153-203. The neutralization epitopes H8, B9 and F2 were also shown to
      overlap by a competitive binding assay. One conserved neutralization epitope, AS
      1, was not exposed on any of the recombinant VP2 deletion fragments and was
      therefore not possible to map. However, the MAbs AS1 and F2 were partly
      competitive indicating that these epitopes are overlapping. All neutralization
      epitopes were independent of a conserved non-neutralization epitope, E4. Our
      results demonstrate that the central third of VP2 contains several partly
      overlapping neutralization epitopes, both variable and conserved among serogroup
      A strains of IPNV.

PMID- 7730801
TI  - Temporal and geographical distribution of measles virus genotypes.
AB  - The nucleotide sequence encoding the C terminus of the nucleocapsid protein of
      measles virus (MV) is the most variable in the genome. The sequence of this
      region is reported for 21 new MV strains and for virus RNA obtained from cases of
      subacute panencephalitis (SSPE) tissue. The nucleotide sequence of a total of 65
      MV strains has been analysed using the CLUSTAL program to determine the
      relationships between the strains. An unrooted tree shows that eight different
      genotypes can be discerned amongst the sequences analysed so far. The data show
      that the C-terminal coding sequence of the nucleocapsid gene, although highly
      variable between strains, is stable in a given strain and does not appear to
      diverge in tissue culture. It therefore provides a good 'signature' sequence for
      specific genotypes. The sequence of this region can be used to discriminate new
      imported viruses from old 'endemic' strains of MV in a geographical area. The
      different genotypes are not geographically restricted although some appear to be
      the mainly 'endemic' types in large areas of the world. In global terms there
      appears to be at least four cocirculating genotypes of MV. The low level of
      divergence in the Edmonston lineage group isolated before 1970 indicates that
      some isolates are probably laboratory contaminants. This applies to some SSPE
      isolates such as the Halle, Mantooth and Horta-Barbosa strains as well as some
      wild-type isolates from that period.

PMID- 7730802
TI  - Effect of alterations in early signal transduction events on the induction of
      procoagulant activity by murine hepatitis virus strain 3 in vitro.
AB  - The induction of macrophage procoagulant activity (PCA) has been shown to
      correlate with the development of fulminant hepatic necrosis after infection with
      murine hepatitis virus strain 3 (MHV-3). However, comparatively little is known
      about the early events in cells after viral infection leading to PCA expression.
      Accordingly, we investigated the early cellular events in the induction of
      macrophage PCA by MHV-3. MHV-3 stimulation of macrophages did not result in a
      detectable increase in intracellular calcium levels nor did stimulation of
      macrophages by calcium ionophores result in induction of PCA, suggesting that
      calcium transients were neither necessary nor sufficient for induction of PCA by
      MHV-3. Treatment of cells with phorbol myristate acetate had no effect on PCA
      induction; however, inhibition of protein kinase C (PKC) by staurosporine or H7
      resulted in attenuation of macrophage PCA following MHV-3 stimulation (P < 0.05
      compared with untreated macrophages), suggesting that although activation of PKC
      alone is insufficient for PCA induction, PKC may be an integral component of PCA
      induction by MHV-3. We have previously demonstrated that dimethyl prostaglandin
      E2 inhibited induction of PCA by MHV-3. In this study, treatment of cells by
      agents that increase intracellular cAMP (forskolin, isobutylmethyl xanthine)
      significantly inhibited PCA induction (P < 0.02). These results demonstrate that
      induction of macrophage PCA by MHV-3 involves PKC, but proceeds independently of
      changes in intracellular calcium, and that PCA expression is down-regulated by
      increases in intracellular cAMP.

PMID- 7730803
TI  - 5' UTR of hepatitis A virus RNA: mutations in the 5'-most pyrimidine-rich tract
      reduce its ability to direct internal initiation of translation.
AB  - The 5'-terminal untranslated region (5' UTR) of the uncapped hepatitis A virus
      (HAV) RNA contains two pyrimidine-rich sequences; one about 20 nucleotides (nt)
      in length in the vicinity of the AUG initiation codon (nt 706-726), and a longer
      one (about 40 nt) encompassing nt 100 to 140. The latter includes a 13 nt 'core'
      sequence (positions 126-138 in the HM175 strain) which is 80% identical to the
      pyrimidine-rich tract of poliovirus type 1 RNA (Mahoney strain). Representative
      cDNAs of the entire 5' UTR of HAV RNA were inserted in the intercistronic region
      of the bi-cistronic plasmid pSV-GH/CAT between the genes coding for the human
      growth hormone (GH) and bacterial chloramphenicol acetyltransferase (CAT). When
      COS-7 cells were transfected with these constructs they transiently expressed CAT
      indicating that the 5' UTR of HAV was efficiently directing internal initiation
      of translation of the reporter gene. Under similar conditions the 5' UTR of
      poliovirus type 2 (Lansing strain) was 30% more efficient in directing the
      expression of the CAT gene. Removal of the 'core' sequence from the 5'-distal
      pyrimidine-rich stretch extending between nt 117 and 131 in the HAV 5' UTR
      reduced the CAT activity in the lysates of transfected cells by 40%, whereas
      point mutations engineered in this segment strongly decreased (80% inhibition)
      the HAV-driven expression of the reporter gene. Limited mutations systematically
      introduced in the reiterated (U)UUUCCC motifs of the 5'-distal pyrimidine-rich
      tract identified two major functional domains extending between nt 100-106 and
      113-119. Substitutions in these hexanucleotides abrogated internal initiation of
      translation, whereas similar changes in the neighbouring domains (nt 107-112 and
      120-126) had no effect on the expression of the reporter gene, suggesting that
      the 5'-most pyrimidine-rich tract is indeed part of the structure(s) recognized
      by ribosomes and associated factors at initiation of translation and that the
      hexanucleotides 100-106 and 113-119 constitute an important part of it. Although
      HAV replicates better at 33 degrees C than at 37 degrees C, incubation of
      transfected cultures at 33 degrees C delayed the expression and slightly reduced
      the level of CAT activity in the cell lysates, but the overall effect of the
      mutations remained unchanged.

PMID- 7730804
TI  - Survey of major genotypes and subtypes of hepatitis C virus using RFLP of
      sequences amplified from the 5' non-coding region.
AB  - A method is described for identifying different genotypes of hepatitis C virus
      (HCV) by restriction endonuclease cleavage of sequences amplified by PCR from the
      5' non-coding region. Using the enzymes HaeIII-RsaI and HinfI-MvaI, followed by
      cleavage with BstU1 or ScrFI, it was possible to identify and distinguish HCV
      genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5 and 6. The method was used to investigate
      the prevalence of these genotypes in 723 blood donors in 15 countries, the
      largest survey to date, and one which covered a wide range of geographical
      regions (Europe, America, Africa and Asia). These results, combined with a review
      of the existing literature, indicate the existence of several distinct regional
      patterns of HCV genotype distribution, and provide the framework for future
      detailed epidemiological investigations of HCV transmission.

PMID- 7730805
TI  - Characterization of an established human hepatoma cell line constitutively
      expressing non-structural proteins of hepatitis C virus by transfection of viral
      cDNA.
AB  - A human hepatoma cell line constitutively expressing proteins of hepatitis C
      virus (HCV) was established by transfection with cDNA encoding part of the virus
      nonstructural (NS) genome region. Proteins consistent with authentic processing
      at NS3/NS4A, NS4A/NS4B and NS4B/NS5A were identified. Pulse-chase experiments
      indicated that the cleavage between NS3 and NS4A occurred first and cleavage at
      other sites followed. Expression of specific surface antigens in response to the
      presence of HCV proteins was analysed by flow cytometry. A significant increase
      in CD26 expression was observed in cells expressing the HCV proteins. CD26 plays
      an important role in cellular signal transduction. Its upregulation in response
      to the presence of HCV proteins may play a role in viral pathology.

PMID- 7730806
TI  - Establishment of a cell line constitutively expressing E2 glycoprotein of
      hepatitis C virus and humoral response of hepatitis C patients to the expressed
      protein.
AB  - A Chinese hamster ovary cell line was established which abundantly expresses the
      second envelope protein (E2) of hepatitis C virus under the control of an
      exogenous promoter. The expressed E2 protein was found to be a glycoprotein of 58
      kDa by immunoprecipitation with sera from patients that had chronic hepatitis C.
      Using this cell line as antigen in immunofluorescence tests, as high as 93% of
      patients with non-A non-B hepatitis had antibodies against E2 protein. In Western
      blots using SDS-denatured E2 protein, however, the detectability of the antibody
      was drastically reduced to 30%. Immunoprecipitation assays and ELISA, using both
      native and denatured E2 protein, revealed that antibodies to E2 protein were
      present in most of the chronic hepatitis C patients and that they reacted only to
      the native forms.

PMID- 7730807
TI  - Morphology and antigenicity of recombinant B19 parvovirus capsids expressed in
      transfected COS-7 cells.
AB  - COS-7 cells transfected with parvovirus B19-simian virus 40 (SV40) hybrid vectors
      have previously been shown to express B19 structural proteins. In this study the
      morphology and antigenicity of B19 proteins expressed in these cells were
      investigated. At 84 h after transfection, approximately 10% of the COS-7 cells
      expressed B19 antigen, and the yield was equivalent to 2 x 10(3) to 2 x 10(5) B19
      particles/transfected cell. The B19 proteins self-assembled into capsids that
      were morphologically and antigenically similar to native B19 virions, and could
      substitute for native antigen in a B19 IgM assay. Recombinant capsids lacking the
      recently described 11 kDa protein also resembled native virions.

PMID- 7730808
TI  - The human papillomavirus (HPV)-6 and HPV-16 E5 proteins co-operate with HPV-16 E7
      in the transformation of primary rodent cells.
AB  - E5 is the smallest transforming protein encoded by the human papillomaviruses
      (HPVs). It has been shown to promote anchorage-independent growth in established
      NIH 3T3 cells, an activity that is enhanced in the presence of epidermal growth
      factor (EGF). It is thought that this activity of E5 is brought about by an
      increase in the half-life of stimulated EGF receptors, possibly through the
      perturbation of receptor processing. Recent studies have also shown that E5 can
      co-operate with HPV-16 E7 to stimulate proliferation of primary rodent cells.
      Using haemagglutinin I epitope-tagged E5 proteins, we have compared the mitogenic
      activity of HPV-6 and HPV-16 E5. Both tagged proteins retain the ability to bind
      to the cellular 16 kDa H(+)-ATPase protein. In addition, both HPV-6 and HPV-16 E5
      retain the ability to co-operate with E7 in primary rodent cells, although HPV-16
      E5 is considerably more active than HPV-6 E5 in these mitogenic assays.
      Interestingly, transfection of a plasmid over-expressing c-Raf appears to be
      capable of functionally substituting for E5 in the co-mitogen assays. Polyclonal
      cell lines derived from baby rat kidney cells co-transfected with E7 and E5 genes
      continue to express both the E5 and E7 mRNA, although the level of E5 expression
      is very low and protein cannot be detected. These polyclonal lines appear to be
      immortal and in some cases demonstrate anchorage-independent growth, an activity
      which is enhanced by the addition of EGF.

PMID- 7730809
TI  - Antigenic and genetic characteristics of H1N1 human influenza virus isolated from
      pigs in Japan.
AB  - Two strains of influenza A virus were isolated from pigs in northern Japan in
      1992. Serological tests showed that the haemagglutinin (HA) and neuraminidase
      (NA) antigens were more closely related to those of recent human H1N1 viruses
      than to those of swine H1N1 viruses. The HA and NA genes of isolate
      A/sw/Obihiro/5/92 were shown to be closely related to those of current human H1N1
      viruses. Evolutionary trees constructed from nucleotide sequences showed that the
      HA and NA genes of A/sw/Obihiro/5/92 were apparently on a branch cluster
      containing human strains isolated between 1990 and 1992.

PMID- 7730810
TI  - Parainfluenza virus type 1 infects olfactory neurons and establishes long-term
      persistence in the nerve tissue.
AB  - A mouse model of Sendai virus infection was adopted to examine the in vivo
      neurovirulence of parainfluenza viruses. A nested polymerase chain reaction
      detected the Sendai virus nucleoprotein gene in the olfactory bulbs of
      intranasally infected mice for at least 168 days post-infection (p.i.) and virus
      specific messenger RNAs for 28 days p.i. Viral proteins were histochemically
      detected in some olfactory neurons for 7 days p.i. They were also found in
      glomeruli of the olfactory bulbs but not in the mitral cells and the tufted
      cells. No virus was detected in the whole brain not including the olfactory
      bulbs. When mice were inoculated with UV-inactivated virus, the viral RNA was
      present in the olfactory bulbs for a short period of 14 days, with no
      demonstrable viraemia. These results demonstrate that the parainfluenza virus
      directly accesses the central nervous system via olfactory neurons and
      establishes long-term persistence in the nerve tissue.

PMID- 7730811
TI  - Monoclonal antibodies to a peptide of human rhinovirus type 2 with different
      specificities recognize the same minimum sequence.
AB  - Monoclonal antibodies (MAbs) raised against a synthetic peptide including
      residues 156-170 of protein VP2 of human rhinovirus type 2 (HRV2) have previously
      been shown to be of differing specificities. The basis for these differences has
      now been examined in greater detail by ELISA, radioimmunoprecipitation and virus
      neutralization. Reactions with a panel of HRV2 mutant viruses indicated that
      substitution of some residues could enhance the apparent activity of one of the
      neutralizing anti-peptide MAbs. For one such substitution, VP2 P164H, there
      appeared to be a correlation between increased neutralizing activity and enhanced
      binding. Mapping experiments identified two overlapping neutralization epitopes
      (amino acids 156-163 and 160-165) and several non-neutralizing epitopes. Although
      some differences in antibody reactivity were due to epitope specificity alone,
      the explanation for others was less obvious. Significantly, the majority of MAbs
      that recognized, and in some cases neutralized, native virus had the same minimum
      binding sequence and critical residue requirement as others which recognized
      virus particles only after distortion. This demonstrates that factors other than
      the linear sequence of the peptide can be crucial in determining the fine
      specificity, and hence biological relevance, of peptide antigens.

PMID- 7730812
TI  - Comparison of bovine coronavirus isolates associated with neonatal calf diarrhoea
      and winter dysentery in adult dairy cattle in Quebec.
AB  - Cytopathic coronaviruses were isolated in HRT-18 cells from bloody faecal samples
      collected from cows in Quebec dairy herds having experienced typical outbreaks of
      winter dysentery (WD). The formation of polykaryons in the infected cell cultures
      was found to be dependent on the presence of trypsin in the medium. The WD
      isolates differed from the prototype Mebus strain of bovine enteropathogenic
      coronavirus (BCV.Meb) in respect to haemagglutination inhibition (HI),
      haemagglutination patterns at 4 degrees C and 37 degrees C, and receptor
      destroying enzyme activity with rat erythrocytes. Other field strains of BCV
      associated with outbreaks of neonatal calf diarrhoea (NCD) also differed from the
      BCV.Meb strain by demonstrating differences in HI. In all cases, no differences
      were detected by virus neutralization and Western immunoblotting. Analysis and
      comparison of the nucleotide and deduced amino acid sequences of the PCR
      amplified haemagglutinin esterase (HE) genes of one representative WD strain
      (BCQ.2590) and two highly cytopathic NCD strains (BCQ.3 and BCQ.571) revealed
      high degrees of similarities (nt and aa sequence homologies > 98%) with the
      BCV.Meb strain. The putative esterase active site FGDS was conserved among these
      four BCV strains, indicating that this domain is probably not a determinant for
      BCV virulence. Six amino acid substitutions occurred between the HE glycoproteins
      of BCV.Meb and BCQ.2590 strains; two proline substitutions occurred respectively
      in the signal peptide (at aa 5) and near the sequences of the putative esterase
      domain (at aa 53).

PMID- 7730813
TI  - Characterization of cassava vein mosaic virus: a distinct plant pararetrovirus.
AB  - Cassava vein mosaic virus (CVMV) was found to be widespread throughout the north
      eastern region of Brazil. The complete sequence of CVMV was determined, and the
      genome was 8158 bp in size. A cytosolic initiator methionine tRNA (tRNA met1)
      binding site that probably acts as a primer for minus-strand synthesis was
      present. The genome contained five open reading frames that potentially encode
      proteins with predicted molecular masses of 186 kDa, 9 kDa, 77 kDa, 24 kDa and 26
      kDa. The putative 186 kDa protein had regions with similarity to the zinc finger
      like RNA-binding domain that is a common element in the capsid proteins and
      similarity to the intercellular transport domain of the plant pararetroviruses.
      The predicted 77 kDa protein had regions with similarity to aspartic proteases,
      reverse transcriptase and RNase H of pararetroviruses. This gene order was
      confirmed by the amplification of similar PCR products from total DNA extracted
      from CVMV-infected cassava plants. The genomic organization of CVMV was different
      from the organization of either the caulimoviruses or badnaviruses. In
      comparisons of the regions with the reverse transcriptase motif, CVMV was grouped
      between the caulimoviruses and badnaviruses. It appears that CVMV is distinct
      from the other well-characterized plant pararetroviruses.

PMID- 7730814
TI  - The nucleotide sequence of the RNA-2 of an isolate of the English serotype of
      tomato black ring virus: RNA recombination in the history of nepoviruses.
AB  - The RNA-2 of a carrot isolate from the English serotype of tomato black ring
      nepovirus (TBRV-ED) has been sequenced. It is 4618 nucleotides long and contains
      one open reading frame encoding a polypeptide of 1344 amino acids. The 5' non
      coding region contains three repetitions of a stem-loop structure also conserved
      in TBRV-Scottish and grapevine chrome mosaic nepovirus (GCMV). The coat protein
      domain was mapped to the carboxy-terminal one-third of the polyprotein. Sequence
      comparisons indicate that TBRV-ED RNA-2 probably arose by an RNA recombination
      event that resulted in the exchange of the putative movement protein gene between
      TBRV and GCMV.

PMID- 7730815
TI  - Transfer of the 3' non-translated region of grapevine chrome mosaic virus RNA-1
      by recombination to tomato black ring virus RNA-2 in pseudorecombinant isolates.
AB  - In grapevine chrome mosaic and tomato black ring viruses (GCMV and TBRV), as in
      many other nepoviruses, the 3' non-translated regions (3'NTR) are identical
      between the two genomic RNAs. We have investigated the structure of the 3'NTR of
      two recombinant isolates which contain GCMV RNA-1 and TBRV RNA-2. In these
      isolates, the 3'NTR of RNA-1 was transferred to RNA-2, thus restoring the 3'
      identity. The transfer occurred within three passages, and probably contributes
      to the spread of randomly appearing mutations from one genomic RNA to the other.
      The site of recombination is near the 3' end of the open reading frame.

PMID- 7730816
TI  - Mutagenesis of the BC1 and BV1 genes of African cassava mosaic virus identifies
      conserved amino acids that are essential for spread.
AB  - The products of three open reading frames encoded by the bipartite geminiviruses
      have been implicated in viral spread: AC2, BV1 and BC1. Alignment of the DNA B
      encoded gene products, BV1 and BC1, from African cassava mosaic virus (ACMV) with
      six other bipartite geminiviruses showed several highly conserved regions.
      Specific amino acids were selected for mutagenic studies to ascertain the
      tolerance of the virus to change and to identify the regions within these two
      proteins required for normal functioning. Various mutant DNA B constructs, and a
      wild-type construct, were inoculated onto three host plant species with an
      equivalent DNA A construct. Three of the mutant constructs were infectious on
      Nicotiana benthamiana and N. clevelandii, but only two induced ACMV disease
      symptoms on N. tabacum cv. Samsun. Sequencing of the viral DNA extracted from the
      sap of systemically infected plants confirmed the maintenance of introduced base
      changes. The amino acid at position 95 on the BV1 gene product was identified as
      non-essential for normal functioning of the protein. The alteration of the amino
      acid at position 145 in BC1 demonstrated the ability of the virus to tolerate a
      conservative change. The lack of tolerance to other changes in amino acids has
      given an indication of the importance of maintaining protein structure for these
      proteins to function normally.

PMID- 7730817
TI  - Sequence comparison of RNA2 of nematode-transmissible and nematode-non
      transmissible isolates of pea early-browning virus suggests that the gene
      encoding the 29 kDa protein may be involved in nematode transmission.
AB  - A cDNA clone containing the complete coding region of RNA2 of the newly described
      TPA56 isolate of pea early-browning virus (English serotype, PEBV-E) has been
      obtained. A plasmid (pFLA56) containing this clone together with the 5' and 3'
      non-coding regions of PEBV isolate SP5 (the type isolate of PEBV-E) and flanked
      by the CaMV 35S promoter and NOS terminator is infectious when co-inoculated onto
      plants with pCaN1, an infectious clone of PEBV SP5 RNA1. Virus containing RNA2
      derived from the cDNA clone of the TPA56 isolate is transmitted by Trichodorus
      primitivus nematodes, whereas virus containing RNA2 from a clone of the SP5
      isolate is not transmitted. Sequencing revealed 11 differences out of 3374
      nucleotides between the transmissible TPA56 and non-transmissible SP5 clones.
      However, only three of the base changes affected the amino acid sequences of
      virus gene products. A single, conservative amino acid change was present in the
      virus coat protein. Two non-conservative changes occurred in the protein of
      molecular mass 29.6 kDa expressed from an open reading frame located down-stream
      of the coat protein gene, suggesting that it has a function in nematode
      transmission and that changes in this protein prevent vector transmission of the
      SP5 isolate of PEBV.

PMID- 7730818
TI  - Surgical approach and nerve palsy in total hip arthroplasty.
AB  - A prospective study of the relation between nerve palsy and the surgical approach
      used for total hip arthroplasty was performed on 1,000 consecutive patients. A
      postoperative neuropathy was diagnosed in eight patients for an overall
      prevalence of 0.8%. The overall prevalence of nerve palsy with the posterior
      approach was 0.6% and 1.0% with the lateral transtrochanteric approach. In both
      primary and revision surgeries, there were no statistical differences between the
      two approaches. Our data suggest that it is the anatomic variations and
      complexity of the reconstruction that are associated with nerve injury and not
      the surgical approach per se. The increased prevalence of nerve palsy seen in
      revision surgeries (1.4%) regardless of the approach supports this position.

PMID- 7730819
TI  - Femoral head autograft in simultaneous primary and revision total hip
      arthroplasty.
AB  - Bilateral total hip arthroplasty during one anesthetic procedure can be
      beneficial in properly selected patients. For patients who have a failed hip
      arthroplasty requiring revision and a contralateral arthritic hip requiring
      primary arthroplasty, bilateral surgery permits the resected femoral head from
      the primary procedure to be used as a fresh autogenous bone-graft during the
      revision procedure. Four patients underwent combined primary hip arthroplasty and
      contralateral revision hip arthroplasty during one anesthetic procedure. The
      femoral head obtained during the primary procedure was used as a structural
      acetabular bone-graft in three patients, and bone slurry was used to fill
      cavitary acetabular defects in one patient. A femoral neck autograft was used to
      reconstruct a calcar defect in one of the patients. After an average follow-up
      period of 27 months, all hips were functioning well with healed bone-grafts and
      stable prosthetic components.

PMID- 7730820
TI  - Autogenous bone banking in a contralateral total hip arthroplasty. A case report.
AB  - The operative technique of autogenous bone banking of a femoral head from a
      symptomatic degenerative hip undergoing a primary total hip arthroplasty into an
      osseous deficiency of an asymptomatic, contralateral, loose acetabular component
      is described. The rationale for bone banking an autogenous femoral head versus
      the use of an allograft or iliac crest autograft at a later date is discussed.

PMID- 7730821
TI  - Mennen plate fixation for fracture of the femoral shaft with ipsilateral total
      hip and knee arthroplasties.
AB  - A method of treatment for a femoral shaft fracture in a patient with well
      functioning ipsilateral total hip and knee arthroplasties is described. Total hip
      and knee arthroplasties are commonly performed, but ipsilateral femoral shaft
      fracture is an infrequent and troublesome complication. Management of these
      fractures is often difficult. Various operative treatments have been described in
      the literature with varying success.

PMID- 7730822
TI  - Charnley low-friction arthroplasty of the hip.

PMID- 7730823
TI  - Activity and socket wear in the Charnley low-friction arthroplasty.

PMID- 7730824
TI  - Osteolysis associated with cemented total knee arthroplasty.

PMID- 7730825
TI  - Lateral skin flap numbness after total knee arthroplasty.
AB  - The authors report the results of a study of lateral skin flap numbness in 25
      consecutive primary total knee arthroplasties following the use of a midline,
      parapatellar incision. All 25 scars were found to have some degree of skin flap
      numbness, with 24 having an affected skin area of greater than 40 cm2. In two
      patients (7%), this was considered a significant problem and there appeared to be
      little improvement with time. The authors therefore feel that lateral skin flap
      numbness is a significant complication of total knee arthroplasty when a midline,
      parapatellar incision is used, and patients should be made aware of this
      complication before surgery.

PMID- 7730826
TI  - Bipolar hip arthroplasty without acetabular bone-grafting for dysplastic
      osteoarthritis. Results after 6-9 years.
AB  - The authors report the clinical and radiographic results of 36 bipolar hip
      arthroplasties after performing excavation of the steep and shallow acetabulum
      without acetabular bone-grafting for dysplastic osteoarthritis. The procedures
      were carried out between 1981 and 1985. Survivorship analysis showed that 84.6 of
      the bipolar hip arthroplasties were retained for 8 years. Twenty-nine patients,
      which were followed for 6-9 years after surgery, were reviewed. Severity of
      acetabular dysplasia was classified according to the method of Crowe. Class 1
      included 17 hips and class 2 included 12 hips. The average preoperative clinical
      score was 49 points. The average postoperative clinical hip score improved to 87
      points after 6 years. Twenty-seven of the 29 hips assessed were classified as
      either excellent or good by Charnley's function score. Stress fracture, due to
      excessive acetabular excavation at the time of surgery, and femoral component
      loosening were major symptomatic complications. The cessation of radiographic
      evidence of migration of the bipolar socket was recognized in 25 of 29 procedures
      at 6 years after surgery (86.2%). Cineradiographic study demonstrated that the
      abduction motion under standing position for 20 of 24 hip joints functioned
      dominantly at the inner-bearing and metallic-stem interface.

PMID- 7730827
TI  - A follow-up study of porous-coated anatomic knee arthroplasty.
AB  - Ninety-four patients (105 knees) having a porous-coated anatomic total knee
      arthroplasty were retrospectively studied. The mean follow-up period was 5.8
      years. The diagnoses were osteoarthritis (90.5%) and rheumatoid arthritis (9.5%).
      There were 80 women and 14 men. The mean age at operation was 58.5 years.
      Clinical evaluation, using the Hospital for Special Surgery knee score along with
      radiography, was used to assess knee status before and after surgery. The
      postoperative mean axial alignment was 3 degrees varus compared with 11 degrees
      varus before surgery. Placement of the prosthetic components was acceptable, with
      the femoral component in 6.5 degrees of valgus and the tibial component in 1.9
      degrees of varus and 1.1 degrees posterior inclination. Complications included
      eight aseptic loosenings, four patellar maltrackings, one patellar fracture,
      eight wound problems, and one extension contracture. Most of the patients' knee
      function improved after surgery. The initial, postoperative range of motion
      improved in patients receiving continuous passive motion (CPM) immediately after
      surgery (P = .03) compared to patients without CPM application; however, the long
      term follow-up data show no significance (P = .06) whether CPM was used or not.
      Age, body weight, degree of arthritic change, and modes of fixation yielded no
      significant influence on the final outcome. The porous-coated anatomic total knee
      arthroplasty is a valuable alternative procedure in the advanced arthritic knee
      when the proper candidates are selected, accurate surgical technique is executed
      and a suitable fixation mode is chosen.

PMID- 7730828
TI  - Interlocked supracondylar intramedullary nails for supracondylar fractures after
      total knee arthroplasty. A new treatment method.
AB  - Supracondylar fractures in patients with total knee prostheses are challenging
      surgical problems for which there has been no single satisfactory method of
      management. The authors present four cases to show that a fully cannulated,
      closed-section, stainless steel supracondylar intramedullary nail can be inserted
      in a closed fashion through a 3 cm longitudinal patellar splitting incision
      between the metal condyles of a nonconstrained femoral component of a total knee
      prosthesis. The nail can be interlocked with percutaneous screws and provides
      primary stability of a supracondylar femoral fracture, even in the presence of
      total knee and total hip prostheses.

PMID- 7730829
TI  - Radiologic study of the accuracy of a tibial intramedullary cutting guide for
      knee arthroplasty.
AB  - Twenty-one caucasian, adult cadaveric tibiae were prepared as for knee
      arthroplasty using an intramedullary cutting guide. The instrumentation was used
      to produce slots in the proximal tibia into which Kirschner wires were placed as
      radio-opaque markers for subsequent anteroposterior and lateral radiographs. The
      anatomic axis of the tibia and lines perpendicular to the wire markers were drawn
      on the radiographs and the angle between the two lines was measured to assess the
      accuracy of the cuts. Seventy-one percent of the tibial cuts were found to be
      within 2 degrees of the anatomic axis on the anteroposterior radiograph (mean,
      2.1 degrees), while on the lateral radiograph, 81% of the cuts were within 2
      degrees (mean, 1.8 degrees). There was a significant tendency to position the
      bone cuts in varus (P < .05), although this did not correlate with varus or
      valgus deformity of the bones. There was no consistent tendency to anterior or
      posterior tilt on the lateral radiograph (P > .05). The results compare favorably
      with those obtained from a specialist unit using an extramedullary alignment
      system. The authors conclude that the tibial intramedullary guide can lead to
      preparation of the proximal tibia for knee arthroplasty as accurately as the
      conventional extramedullary system.

PMID- 7730830
TI  - Resection specimen analysis of proximal tibial anatomy based on 100 total knee
      arthroplasty specimens.
AB  - Although it is known that there is some asymmetry of the tibial plateau, most
      total knee arthroplasty designs currently have a symmetric tibial component.
      Using resection specimen analysis of the tibial plateau from 100 total knee
      arthroplasty specimens, the authors have examined the tibial plateau to further
      delineate, quantitatively, the medial and lateral tibial configuration.
      Unmagnified radiographs of each of the specimens were produced. A line was drawn
      along the mediolateral axis. The midpoint and points 10, 20, and 30% from the
      medial and lateral peripheries were then calculated. The average anteroposterior
      medial 10, 20, and 30% dimensions were 3.79, 4.74, and 5.06 cm, respectively. The
      average anteroposterior lateral 10, 20, and 30% dimensions were 3.48, 4.10, and
      4.16 cm, respectively. The ratios of the lateral/medial anteroposterior distances
      at 10, 20, and 30% from the periphery were 92.10, 86.77, and 82.46%,
      respectively. A total knee arthroplasty system that recognizes the difference in
      the medial and lateral tibial plateaus and designs a prosthesis to account for
      the smaller, lateral tibial plateau may achieve the goal of maximizing tibial
      coverage as well as eliminate the problems associated with a symmetric design.

PMID- 7730831
TI  - Position of the knee joint after total joint arthroplasty.
AB  - A method for assessing knee joint position after surgery using the preoperative
      long-leg radiograph and the postoperative knee radiograph is described.
      Assessment of the formula has shown a near perfect correlation between the
      calculated position on the long-leg radiograph compared with the measured
      position for 44 knees. Three hundred eighteen knees after total joint
      arthroplasty were retrospectively reviewed and the postoperative position was
      determined. The preoperative position of the mechanical axis was 14.5 +/- 37.3 mm
      medial to the knee joint center. Using the standing knee radiograph the
      postoperative position of the mechanical axis was 3.07 +/- 9.2 mm lateral to the
      knee joint center, while the portable radiograph placed the mechanical axis 4.5
      +/- 12.4 mm medial to the knee joint center. There was a highly significant
      difference in the position of the knee joint center depending on the radiograph
      used for calculation (standing or portable). The difference between the two means
      was not due to opening of the knee joint, but likely due to change in the
      rotation of the knee in the presence of knee flexion. This series of the knee
      arthroplasties has a low projected rate of aseptic failure.

PMID- 7730832
TI  - Alterations in femoral strain, micromotion, cortical geometry, cortical porosity,
      and bony ingrowth in uncemented collared and collarless prostheses in the dog.
AB  - The effects of a collared femoral endoprosthesis in uncemented total hip
      arthroplasty were evaluated in 12 dogs. This experimental study compared the
      biomechanic and histologic responses between collared and collarless femoral
      prostheses 4 months after implantation. Implant stability (micromotion) and
      cortical surface strain were evaluated immediately and 4 months after
      implantation in a simulated postoperative condition, whereas bone ingrowth,
      cortical porosity, and cortical remodeling were assessed after 4 months only.
      There were no significant differences in implant stability or cortical surface
      strains when the collared and collarless groups were compared acutely or after 4
      months (P > .05). There were also no significant differences in percent fill,
      bony ingrowth, or cortical geometry after 4 months (P > .05). There was a
      significant increase in cortical porosity measured from the proximal femur after
      4 months for both the collared (P = .0002) and collarless groups (P = .009) and
      when both groups were compared (collarless, 8.2% and collared, 5.8%; P = .03).
      The results suggest that a collar may be beneficial in decreasing the cortical
      remodeling that occurs in the proximal femoral cortex after implantation of an
      uncemented total hip arthroplasty.

PMID- 7730833
TI  - Changes in bone mineral density of the distal femur following uncemented total
      knee arthroplasty.
AB  - The aim of the study was to quantitate changes in bone mineral density (BMD) in
      the distal femur following uncemented porous-coated total knee arthroplasty.
      Eight patients with total knee arthroplasties (PCA Primary, Howmedica,
      Rutherford, NJ) (female:male ratio, 6:2; mean age, 70 years; range, 51-77 years)
      were scanned by dual-photon absorptiometry within 3 months after surgery and at 2
      years. An average decrease of 36% (P = .01) was found in BMD behind the anterior
      flange of the femoral prosthesis. Proximal to the fixation pegs, BMD increased by
      22% (P = .12), but behind the posterior flange of the femoral component, BMD
      remained unchanged (P = .53). Stress shielding anteriorly in the distal femur
      occurred in all patients examined 2 years after surgery, and the increase in BMD
      proximal to the fixation pegs was probably a result of increased and altered
      mechanical loading.

PMID- 7730834
TI  - Intraarticular carcinogenesis bioassays of CoCrMo and TiAlV alloys in rats.
AB  - Wear-debris powders of cobalt-chromium-molybdenum (CoCrMo) and titanium-aluminum
      vanadium (TiAlV) alloys, which are widely used for orthopedic implants (eg, hip
      and knee prostheses), were tested for carcinogenic activity following
      intraarticular administration (20 mg/rat) to groups of 44 male Fischer-344 rats
      (Charles River Breeding Laboratories, North Wilmington, MA). Control groups
      received similar intraarticular injections of either a noncarcinogen (manganese
      powder, negative control rats) or a potent carcinogen (nickel subsulfide powder,
      positive control rats). The experimental groups of 8-12 rats were observed for 24
      months after injection. No local tumors developed at the injection site in the
      negative control rats or in rats that received the CoCrMo or TiAlV powders;
      poorly differentiated or pleomorphic sarcomas developed at the injection site in
      10 of the 12 positive control rats that were treated with nickel subsulfide.
      Incidences of primary tumors distant from the injection site did not differ
      significantly among the experimental groups. This study shows that, under
      experimental conditions, any carcinogenic activity of CoCrMo or TiAlV wear-debris
      powders is weak in comparison to nickel subsulfide. Based on this study and
      observations in other laboratories, intraarticular administration of test
      materials to rats provides a practical, reliable, and biologically relevant
      method for carcinogenesis testing of biomaterials used for orthopedic implants.

PMID- 7730835
TI  - Titanium contamination of recycled Cell Saver blood in revision hip arthroplasty.
AB  - The use of Cell Saver blood during revision hip arthroplasty has many benefits,
      both medical and economic. After a review of the current literature, to our
      knowledge, no case of metallic debris has been reported in the blood after
      complete treatment with the Haemonetics Cell Saver (Braintree, MA) and
      appropriate filter system. A case of total hip revision of a loose, cemented
      acetabular component with a commercially pure titanium metal backing and a
      titanium alloy plasma-spray textured surface was undertaken. The titanium alloy
      femoral component was not visibly loose and was not revised. The joint lining
      tissues were black. Throughout the procedure, the operative site was suctioned
      with a double-lumen heparinized catheter that delivered blood and other materials
      to a Haemonetics Cell Saver 3 Plus. The reservoir and filter unit used were the
      compatible Bentley BCR-3500 (Baxter, Irvine, CA), a system capable of filtering
      particulates down to 20 microns. Prior to infusion of the salvaged blood, many
      large black clumps of material were observed mixed in the blood. Some measured 10
      x 5 x 5 mm and could easily be seen macroscopically. Light microscopy
      demonstrated red blood cells with intermixed neutrophils, and black foreign
      material scattered as separate particles and within the cytoplasm of the
      scattered histiocytes. Energy dispersive analysis of the black material confirmed
      the composition as primarily titanium with minute quantities of copper, iron,
      phosphorous, and sulfur. A scanning electron photomicrograph of one of the
      specimens demonstrated a large conglomerate, approximately 2,000 microns in
      diameter, composed primarily of titanium and organic material.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7730836
TI  - Techniques in arthroplasty. Use of an articulated PMMA spacer in the infected
      total knee arthroplasty.

PMID- 7730837
TI  - Methyl methacrylate levels in the breast milk of a patient after total hip
      arthroplasty.
AB  - Blood levels of methyl methacrylate (MMA) are known to be transiently elevated in
      patients having undergone total hip arthroplasty using cement fixation. However,
      it is not known whether MMA is present in the breast milk of lactating women
      after this procedure. The authors studied an otherwise healthy lactating 29-year
      old mother 5 months postpartum who had undergone total hip arthroplasty because
      of walking limitations due to congenital hip dysplasia. Less than 0.0005
      micrograms/mL of MMA was found in her breast milk 36 hours after the procedure.
      If the negative findings in this case can be confirmed in a larger trial, the
      current practice of discontinuing breast-feeding after arthroplasty may be
      reconsidered.

PMID- 7730838
TI  - Molecular genetic diagnosis of infected total joint arthroplasty.

PMID- 7730839
TI  - Retrograde intramedullary nailing of supracondylar femur fractures above total
      knee arthroplasty. A preliminary report of four cases.
AB  - Four supracondylar fractures of the femur in three patients with total knee
      arthroplasties were treated by retrograde intramedullary nailing using an
      interlocking renamed nail (GSH Nail, Smith and Nephew Richards, Memphis, TN)
      specifically designed for fractures of the distal femur. Three cases were acute
      fractures and one was a refracture through a screw hole of a previously plated
      supracondylar fracture. All fractures healed and there were no complications. The
      procedure is performed by closed nailing using fluoroscopic guidance with the
      nail placed through the intercondylar notch of the femoral prosthesis and
      interlocking to the fracture fragments with a percutaneous targeting device. The
      advantages are that the procedure is performed by closed techniques that preserve
      the fracture hematoma and reduce operative blood loss, the fracture is stabilized
      by a load-sharing nail, and immediate motion with limited weight bearing is
      possible.

PMID- 7730840
TI  - The emergence of a new species: the professional meta-analyst.

PMID- 7730841
TI  - The professional meta-analyst: an evolutionary advantage.

PMID- 7730842
TI  - Responsiveness and calibration of the General Well-Being Adjustment Scale in
      patients with hypertension.
AB  - We examined the discriminant ability and responsiveness of the General Well-Being
      Adjustment Scale in patients enrolled in a randomized clinical trial of
      antihypertensive therapy. We also tried to translate the effects of physical
      symptoms on general well-being. This secondary analysis used demographic,
      clinical, physical symptom, and general well-being data for 545 white, male
      hypertensive patients. General well-being was measured by the General Well-Being
      Adjustment Scale (GWB) collected on 2 occasions over 8 weeks of treatment.
      Patients with any one of 14 physical symptoms or problems, compared to those
      without symptoms, had lower GWB scores (p < 0.003 to p < 0.0001). Decreases of
      2.83-8.76 points in GWB scores were observed in patients developing physical
      symptoms over the 8 week study period (p < 0.05 to p < 0.0001). These effects
      were demonstrated in patients developing cold sensitivity, sexual problems, chest
      pain, shortness of breath, loss of taste, nausea, hot or cold spells, numbness
      and tingling, dry mouth, blurred vision, and dizziness. We conclude that the GWB
      is responsive to clinically meaningful changes in symptoms and may provide a more
      complete evaluation of the effects of medical treatment. The GWB is a valid and
      responsive measure of health status outcomes in the evaluation of
      antihypertensive treatment.

PMID- 7730843
TI  - Sensitivity and specificity of diagnostic tests in acute maxillary sinusitis
      determined by maximum likelihood in the absence of an external standard.
AB  - This study shows how to obtain maximum likelihood estimates of test sensitivities
      and specificities in case of lack of an external standard, using the Expectation
      Maximisation (EM) algorithm. This method is used to compare four diagnostic tests
      in patients suspected of acute maxillary sinusitis. Data were analyzed from
      published studies. Antral aspiration is the test with the highest diagnostic
      value. The diagnostic value of a positive clinical examination (according to
      explicit criteria) and of a positive radiograph or ultrasound are comparable. A
      negative radiograph is of more diagnostic value than a negative clinical
      examination or ultrasound. The width of the confidence intervals may be too
      small, due to model deviations which may give incorrect standard errors. However,
      the estimated likelihood ratios adequately reflect the relative value of the
      diagnostic tests considered, even when the assumption of independence is dropped.

PMID- 7730844
TI  - Estimation of CHD risk in a French working population using a modified Framingham
      model. The PCV-METRA Group.
AB  - We adapt a recent model from the Framingham study (Circulation 1991; 83: 356-362)
      to predict CHD in France for both sexes over a large age range. Calculations were
      based on data from the French PCV-METRA study. In France, the Paris Prospective
      Study model could predict CHD but only for men aged 43-53 years. Applied to men
      43-53 years from the PCV-METRA, the Framingham model estimated a 5-year CHD risk
      (4%) lower than the risk reported in the Framingham sample, but significantly
      higher than the risk estimated by the French model (2%). Differences in estimated
      CHD risk between the Framingham and the PCV-METRA samples were explained for only
      30% by adjustment on major CHD risk factors (mainly HDL-cholesterol and tobacco).
      Modifying the intercept in the Framingham model, agreement with estimated risk by
      the French model was improved from 29 to 80%. By an appropriate change of the
      intercept, the Framingham model might be used to estimate CHD risk in other
      populations.

PMID- 7730845
TI  - General practitioners' decision making for mental health problems: outcomes and
      ecological validity.
AB  - A major problem in the field of medical decision making is the ecological
      (external) validity of the results. In a Judgement Analysis study on mental
      health, vignettes were used to capture the decision strategies of 28 General
      Practitioners (GPs). Two different decision strategies for mental health problems
      could be distinguished. Although the results were statistically satisfactory and
      met the assumptions of Judgement Analysis, it was considered necessary to
      determine the ecological validity of the vignettes. Video tapes (n = 90) of GP
      consultations were scored in terms of the units of information (cues) which had
      been used in the vignette study. Additional data gave access to the judgements of
      the GPs, which were comparable to the judgements obtained in the vignette study.
      Results showed that the weights given to the different cues in the vignette study
      were situated within the confidence interval of the weights from the video study.
      Thus indicating that the results obtained from the vignette study have ecological
      validity.

PMID- 7730846
TI  - Study of quality of life on rural hypertensive patients. Comparison with the
      general population of the same environment.
AB  - A comparative study about quality of life was made in the community of Riosa-
      north of Spain--on two groups of subjects: one affected by hypertension (n =
      115), stage I and II of WHO, and another of the general population, matched in
      age, sex and residence with the former group and of the same size. The subjects
      with loss of self-care or mobility were excluded. The quality of life was
      evaluated with a standardized measurement approach referring to the spheres of
      physical, emotional, social and sexual functions. With this study the validation
      of the Spanish version of the questionnaire was made and the results obtained
      were found to be more or less the same as those reported by authors in other
      European countries of similar sociodemographic conditions. Hypertensive patients
      reported significant lower scores of quality of life than the general population
      in more than half of the dimensions explored: well-being and physical capacity,
      social functioning, positive mood and psychological functioning. In conclusion,
      despite the many limitations inherent to this area of research, a standardized
      and valid measure of relevant aspects of quality of life in the general
      population and especially in patients with hypertension, is available in the
      Spanish language.

PMID- 7730847
TI  - Correlates of Mini-Mental Status Examination scores among elderly demented
      patients: the influence of race-ethnicity.
AB  - Data on 1888 patients seen at Alzheimer's Disease Diagnostic and Treatment
      Centers in California were used to examine possible differences in Mini-Mental
      State Examination (MMSE) results for different racial-ethnic groups. White
      patients had scores less indicative of dementia than Black and Hispanic patients
      using the standard 23 cutting point on the MMSE. However, there were no
      differences among these groups in the percentages clinically diagnosed as
      demented. The difference in the percentage of Whites vs Blacks and Hispanics
      categorized as demented by the MMSE was not accounted for by education,
      occupation, age, sex, or other variables tested, even though these variables were
      correlated with MMSE scores. Our data suggest that clinicians should consider
      MMSE scores for Black and Hispanic patients an underestimate of their cognitive
      capabilities relative to that of White patients.

PMID- 7730848
TI  - Long-term prognosis after peri-operative cardiac complications.
AB  - The objective was to document the 5 year prognosis of patients who had cardiac
      complications after non-cardiac surgery. DESIGN: 5-year follow-up of 218 patients
      originally enrolled in a prospective study to identify risks factors for peri
      operative complications. SETTING: an academic medical center. Participants were
      hypertensives and diabetics who underwent elective surgery between 1982 and 1985.
      In the original study, patients were evaluated pre-operatively, monitored intra
      operatively by an independent observer, and followed daily for 7 days post
      operatively according to a standard surveillance protocol. Outcomes were judged
      by assessors blinded to the pre-operative status and intra-operative course.
      Patients were interviewed at 3 and 5 years post-operatively. Patients with post
      operative cardiac complications had significantly higher rates of overall
      mortality, mortality attributable to cardiac causes (MI, CHF, arrest), and
      mortality attributable to other cardiovascular causes (stroke, renal failure)
      than patients without cardiac complications. For example, at 5 years 11% of those
      patients without post-operative cardiac complications had cardiac deaths, in
      contrast to 45% of those patients with post-operative cardiac complications.
      Proportional hazards analysis demonstrated that post-operative cardiac
      complications remained a significant predictor of cardiac (p < 0.001) and
      cardiovascular (p < 0.0001) mortality controlling for pre-operative cardiac
      disease, other non-cardiovascular comorbid diseases, age, sex, diabetes, and pre
      operative renal insufficiency or stroke. Similarly, patients with post-operative
      non-fatal cardiac complications had higher rates of cardiac or cardiovascular
      events during the 5 year follow-up period. We conclude that post-operative
      cardiac complications have a significant adverse long-term prognostic impact
      comparable to the prognostic impact of myocardial infarction, ischemia or
      congestive failure in the non-operative setting. Understanding these events could
      be an important factor in identifying patients at high risk for subsequent peri
      operative complications.

PMID- 7730849
TI  - Socio-economic status and risk factors for cardiovascular disease: a multicentre
      collaborative study in the International Clinical Epidemiology Network (INCLEN).
      The INCLEN Multicentre Collaborative Group.
AB  - As part of a multicentre collaborative study of risk factors for cardiovascular
      disease (CVD) in the International Clinical Epidemiology Network (INCLEN), each
      of 12 Centres in 7 countries examined the relationship between CVD risk factors
      and socio-economic variables. Each Centre (three in Thailand, two each in China,
      Chile and Brazil and one each in the Philippines, Indonesia and Colombia)
      examined approx. 200 men aged 35-65 drawn at random from a population within
      their locality (not designed to be necessarily representative of the general
      population). Standardized measures of CVD risk factors included body mass index
      (BMI), blood pressure, blood cholesterol and cigarette smoking habits. Education,
      occupation and current income were grouped into ordinal categories of socio
      economic status according to standard protocol guidelines, and comparisons were
      made between risk factor levels within each of these categories. Many of these
      populations had higher levels of education (as a marker of socio-economic status)
      than would the general population of their country. For both BMI and blood
      cholesterol there were a number of centres which showed positive associations
      with socio-economic status. These were predominately in China or urban or rural
      South East Asia. For blood pressure and cigarette smoking the associations with
      socio-economic status tended to be negative, more in line with the direction of
      association seen in the "Developed" World. The high risk factor levels found in
      these populations, particularly the alarming prevalence of cigarette smoking in
      Asia and the high cholesterol levels in Latin America and Urban S.E. Asia suggest
      that CVD will emerge as a major public health problem in the Developing
      World.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730850
TI  - Neck trouble in machine operating, dynamic physical work and sedentary work: a
      prospective study on occupational and individual risk factors.
AB  - A prospective study on the effects of occupational and individual factors on neck
      trouble was carried out among 1832 men representing static work with whole-body
      vibration (machine operators), dynamic physical work (construction carpenters)
      and sedentary work (office workers). Neck trouble and occupational and individual
      factors were inquired about via postal questionnaires in 1984 and 1987. Machine
      operating was associated with an increased risk to contract severe neck trouble,
      and machine operating and dynamic physical work were associated with persistently
      severe neck trouble. Other predictors for contracting severe neck trouble were
      age and current smoking. Physical exercise decreased the risk of persistently
      severe neck trouble. The results of our prospective study confirm the role of
      physical factors in neck trouble.

PMID- 7730851
TI  - The Disability Rating Index: an instrument for the assessment of disability in
      clinical settings.
AB  - The purpose of this study was to evaluate an instrument for assessment of
      physical disability, mainly intended for clinical settings, the Disability Rating
      Index (DRI). Healthy persons (n = 1092), both white and blue collar workers, and
      patients (n = 366) with different levels of physical capacity, were assessed.
      Most of the patients (n = 303) underwent rehabilitation programmes for
      neck/shoulder/low-back pain but some (n = 47) were arthritis patients waiting for
      hip or knee replacement surgery, or wheelchair patients with multiple sclerosis
      (n = 16). The reliability was investigated by test-retest studies, intra- and
      inter-rater and internal consistency studies. Five construct validity tests were
      carried out: a discrimination study; a converging validity test; a test for
      sensitivity to small alterations in health status; and two correlational validity
      tests. Correlation of the self-reported DRI to the actual performance in similar
      activities was carried out. Responsiveness was tested by correlation of the DRI
      before/after replacement surgery for arthritis. The test-retest correlations were
      0.83-0.95 in the studies, including correlation of different versions. The intra-
      and inter-rater reproducibility was 0.98 and 0.99 respectively. The Kruskal
      Wallis test in the discrimination study yielded p < 0.0001. More than 90% of the
      respondents completed the questionnaire correctly. Correlation of the DRI to the
      Functional Status Questionnaire was 0.46. The responsiveness was excellent, p =
      0.0001. The DRI proved to be a robust, practical clinical and research instrument
      with good responsiveness and acceptability for assessment of disability caused by
      impairment of common motor functions.

PMID- 7730852
TI  - Malnutrition and subsequent ischemic heart disease in former prisoners of war of
      World War II and the Korean conflict.
AB  - The harsh treatment of former prisoners of war (POWs) of World War II and the
      Korean conflict resulted in severe malnutrition. Although rarely linked to
      specific long-term medical problems, a specific marker of malnutrition, self
      reported lower limb edema (presumably due to a vitamin B deficiency) was
      associated with a three-fold increase in subsequent death attributed to ischemic
      heart disease (IHD) during the follow-up period from 1967 through 1975. Although
      there is at present no medical basis for linking edema, which is perhaps a marker
      for some unmeasured risk factor, to subsequent IHD, this finding may nonetheless
      have medical implications for the group of former POWs and other populations with
      severe dietary deficiency. It also suggests there may be a need to reexamine
      currently held theories on malnutrition and subsequent chronic disease.

PMID- 7730853
TI  - Quality-of-life following thoracotomy for lung cancer.
AB  - Contrary to the issues of perioperative morbidity and survival following surgery
      for lung cancer, little attention has been given to quality-of-life. To address
      this, quality-of-life was assessed preoperatively and 1, 3, 6 and 9 months
      postoperatively in a cohort of 117 consecutive subjects who underwent thoracotomy
      with a certain or presumptive diagnosis of lung cancer. Those with cancer (n =
      91) confirmed at thoracotomy were contrasted to those without (n = 26). Moderate
      to severe dyspnea, reported in 14% preoperatively, increased to 34% at 1 and 3
      months (p < 0.005) but returned to approximately 10% at 6 and 9 months.
      Similarly, activities of daily living were impaired in 11% preoperatively; this
      disability increased to 21% at 1 month (p < 0.005), and returned to baseline at 6
      and 9 months. Those with cancer compared to those without a postoperative
      diagnosis of cancer had similar quality-of-life preoperatively but deteriorated
      more in the postoperative period. This study demonstrates that important
      deterioration in quality-of-life occurs during the first 3 months postoperatively
      in those with a final diagnosis of cancer but improvement back to baseline can be
      expected thereafter.

PMID- 7730854
TI  - A method for partitioning cancer mortality trends by factors associated with
      diagnosis: an application to female breast cancer.
AB  - U.S. cancer mortality data derived from information recorded on death
      certificates are frequently relied upon as an indicator of progress against
      cancer. A limitation of this measure is the lack of information pertaining to the
      onset of disease, such as year-of-diagnosis, age-at-diagnosis, stage of disease
      at diagnosis and histology of lesions. However, population-based cancer
      registries collect these types of data and allow the calculation of an incidence
      file based mortality rate. This incidence-based mortality rate allows a
      partitioning of mortality by variables associated with the cancer onset. Breast
      cancer incidence-based mortality measures are created and compared to mortality
      rates based on death certificates over a comparable time period. Novel mortality
      measures, such as mortality rates by stage-at-diagnosis, age-at-diagnosis and
      year-of-diagnosis, are used to illustrate the value of this approach.

PMID- 7730855
TI  - Age-specific mortality rate comparisons: is there a fallacy?

PMID- 7730856
TI  - Cross-cultural validation for quality of life.

PMID- 7730857
TI  - Science, policy, and ethics: the case of environmental tobacco smoke.
AB  - The successful campaign against smoking will long be celebrated as a landmark
      achievement of public health. Recently, a prominent component of this campaign
      has been the portrayal of environmental tobacco smoke as a major health risk. To
      this day, however, the scientific basis for this later contention remains
      speculative. The elevation of heuristic hypotheses into official precepts raises
      an intriguing ethical question: Should a claim of best intentions justify
      representing conjecture as scientific knowledge in public policy formulation?

PMID- 7730858
TI  - Environmental tobacco smoke: a public health conspiracy? A dissenting view.

PMID- 7730859
TI  - Respiratory health effects of passive smoking: EPA's weight-of-evidence analysis.
AB  - After an extensive review and assessment of the scientific evidence on the
      respiratory health effects of passive smoking, the U.S. Environmental Protection
      Agency has determined that the widespread exposure to environmental tobacco smoke
      in the United States presents a serious and substantial public health impact. The
      Environmental Protection Agency concluded that environmental tobacco smoke causes
      lung cancer in adult nonsmokers and increases the risk for a variety of noncancer
      respiratory disorders, especially in children. This article reviews evidence
      presented in the Environmental Protection Agency's 1992 report on the respiratory
      health effects of passive smoking and responds to critical allegations levied by
      Gio Gori in his article "Science, policy, and ethics: the case of environmental
      tobacco smoke", appearing in the same issue of this journal. Several recent
      studies appearing since the cutoff date for inclusion in the EPA report are also
      discussed.

PMID- 7730860
TI  - Associations of low formal education level and poor health status: behavioral, in
      addition to demographic and medical, explanations?

PMID- 7730861
TI  - Association of education with incidence of cognitive impairment in three
      established populations for epidemiologic studies of the elderly.
AB  - We analyzed the association of education, occupation, and sex with incidence of
      cognitive impairment using data from three communities in the Established
      Populations for Epidemiologic Studies of the Elderly (EPESE) projects (New Haven,
      East Boston, and Iowa). Participants were initially interviewed in 1981-1983,
      with follow-up 3 and 6 years later. Incident cognitive impairment was defined on
      the basis of either: (1) increase in the number of errors in Short Portable
      Mental Status Questionnaire (SPMSQ) (i.e. from a baseline level below the cutoff
      value to a score above the cutoff), or (2) inability to respond to interview
      questions at a follow-up contact (requiring a proxy informant), or (3) death with
      a recorded diagnosis of a dementing illness. In multiple logistic regression
      models, the major factors predicting the development of cognitive impairment were
      advanced age, any errors on baseline SPMSQ, 8 or fewer years of education, and
      occupation. Education and occupation remained significant predictors after
      controlling for age, site, sex, stroke, and baseline SPMSQ score.

PMID- 7730862
TI  - Inter- and intraobserver variability in the interpretation of computed tomography
      of the lumbar spine.
AB  - In order to assess the variability in interpreting lumbar CT-scans, two
      radiologists and two rheumatologists examined the same set of 40 CT-scans and
      evaluated the presence of primary abnormalities using pre-established criteria.
      Inter- and intraobserver concordance was assessed using kappa statistics.
      Interpretation of herniated nucleus pulposus appeared reliable in this study
      (interobserver and intraobserver kappa statistics approximately 0.7 and 0.9,
      respectively). Conversely, significant variability of interpretation was seen in
      many findings often considered important in benign low-back pain or sciatica.
      Particularly low levels of agreement (interobserver kappa statistics lower to
      0.20) were found for facet joint osteoarthritis and spinal stenosis. Since
      herniated nucleus pulposus appeared as the only reliable CT finding, lumbar CT
      ordering should therefore be currently restricted to confirmation and
      localization of herniated nucleus pulposus, especially when surgery or any other
      invasive intervention is planned to treat prolonged sciatica.

PMID- 7730863
TI  - Does non-diabetic hyperglycemia predict future IHD? Evidence from the Caerphilly
      and Speedwell studies.
AB  - We have examined the risk of subsequent ischemic heart disease (IHD) in men
      according to their initial fasting plasma glucose level in a prospective cohort
      study (Caerphilly Collaborative Study) of 4860 middle aged men from South Wales
      and Bristol, U.K. Ninety-four men reported themselves to be diabetic at initial
      screening and fasting venous plasma glucose levels were determined in these men
      and in a further 4519 non-diabetic men. At follow-up new IHD events occurred
      twice as commonly in diabetics compared to non-diabetics and overall mortality
      was increased 4-fold. Among non-diabetics however, increased IHD events only
      occurred in men with fasting values at the upper end of the distribution of
      baseline plasma glucose values [at 6.8 mmol/l (122 mg/dl) or more]. This
      association was reduced, but remained statistically significant, after adjusting
      for factors associated with plasma glucose levels; body mass index, plasma
      triglyceride, smoking habit and pre-existing IHD. In conclusion there is no
      evidence of a consistent, graded increase in risk of IHD by initial fasting
      plasma glucose level although the risk is significantly increased in men with
      baseline plasma values at 6.8 mmol/l (122 mg/dl) or more, and also in diabetics.
      This study suggests that such levels probably represent a pre-diabetic state in
      many individuals. Appropriate non-pharmacological intervention may be useful in
      halting the progression to the diabetic state, although this should be tested in
      experimental studies.

PMID- 7730864
TI  - Diagnostic accuracy of predicting coronary artery disease related to patients'
      characteristics.
AB  - Patients' demographic and clinical characteristics may affect diagnostic accuracy
      of cardiologists. We asked a group of experienced cardiologists from three
      institutions to estimate the pretest probability of coronary artery disease in
      257 patients referred for diagnostic coronary angiography and with no history of
      previous myocardial infarction nor valvular heart disease. Physicians pretest
      estimates were compared with the diagnostic findings of coronary angiography. We
      tested the influence of five variables on the accuracy of the pretest estimates:
      age, sex, chest pain characteristics, rest electrocardiogram and
      electrocardiographic exercise test result. Cardiologists tended to overestimate
      the presence of coronary artery disease and this tendency was particularly
      remarkable in the group of patients showing a negative exercise test. Pretest
      diagnostic accuracy was 0.72 when the test result was negative and 0.85 when the
      test result was positive (95% confidence interval of the difference 0.03 to 0.23;
      p < 0.001). The diagnosis of coronary artery disease was also more accurate for
      male than for female patients (0.81 vs 0.70; 95% confidence interval of the
      difference 0.02 to 0.21; p < 0.02). Characteristics of chest pain, age and rest
      electrocardiogram did not affect the level of pretest diagnostic accuracy.
      Cardiologists should be cognizant of correctly interpreting a negative exercise
      test and the clinical data of female patients; in both cases, they should move
      circumspect of the diagnosis of coronary artery disease.

PMID- 7730865
TI  - A prospective population based study of gender differential in mortality from
      cardiovascular disease and "all causes" in asymptomatic hyperglycaemics.
AB  - There have been few prospective epidemiological studies of asymptomatic
      hyperglycaemia as a risk factor for cardiovascular disease and all causes
      mortality in women. Gender-specific all causes, cardiovascular disease (CVD),
      ischaemic heart disease (IHD) and stroke mortality rates and relative risks for
      asymptomatic hyperglycaemics (top 5%) have been compared to normoglycaemics
      (bottom 95%) during a mean follow-up of 11.6 years (range 10-14) among 4696 men
      and 5714 women aged 45-64 at entry in the west of Scotland. Univariate analysis
      showed that asymptomatic hyperglycaemia was associated with increased risk of all
      causes, CVD, IHD and stroke mortality in both genders. The degree of this
      association was greater in women than in men. Using multiple logistic regression
      (MLR) analysis to take into account differences in age, systolic (SBP) and
      diastolic blood pressure (DBP), serum cholesterol, body mass index (BMI), and
      cigarette smoking, high causal blood glucose level was still a significant risk
      factor for CVD mortality in both genders. It was also a significant risk factor
      for all causes, IHD and stroke mortality in women but not in men. This study
      shows that to a lesser degree asymptomatic hyperglycaemia shows the same gender
      differentials in risk of mortality as have been demonstrated amongst known
      diabetics.

PMID- 7730866
TI  - The development of a short generic version of the Sickness Impact Profile.
AB  - This study concerns the development of a short version of a well-known and much
      used clinimetric instrument called the Sickness Impact Profile (SIP). The SIP is
      a generic measure of functional status. Based on findings of a principal
      components analysis of over 800 SIPs from a multi-diagnostic population, a
      selection of 68 items divided over 6 dimensions was made and initially tested. As
      no support was found for the statistical validity of the categorical structure of
      the original SIP, a new structure, discovered through principal components
      analysis, was used as the basis for selecting items. Comparison of the scores on
      the selection with information provided by the original SIP showed very promising
      results: the 68 item selection may serve as a valid short SIP-version.

PMID- 7730867
TI  - Sartwell's incubation period model revisited in the light of dynamic modeling.
AB  - The objective is to look into the well-known robustness of Sartwell's disease
      incubation period (IP) lognormal model. A new approach is proposed that embeds
      the pathogenesis of infection into the framework of percolation theory derived
      from the physical sciences. A two-step model of the individual disease process is
      proposed. The first step has a stochastic basis: it is aimed at establishing the
      threshold position of subjects bound to be diseased. Agent and host factors
      entertain and help the process reach the threshold. They include all the biologic
      risk factors (age, exposure dose and intensity, route of inoculation, etc.) to
      which Sartwell's model is usually found robust. The threshold is the point of no
      return of the disease process. The threshold provides the initial conditions of
      the second step. The second step traces the evolution of the pathologic process
      until disease onset: it is based on a nonlinear deterministic model that
      progressively unfolds the individual fates. As a chaotic regime is embedded into
      the model and as chaos unavoidably develops at some time entailing disease onset,
      the IP distribution becomes independent of the initial conditions laid out at the
      threshold. Unpredictable disease time courses and onsets are obtained. Biological
      examples supporting the model are provided. A simulation of 1000 pathologic
      processes is undertaken according to a simple birth-and-death process of
      microorganisms or cancer cells. As expected, a lognormal fits the IP distribution
      over a wide range. A lack of lengthy IPs is, however, observed. A simple
      multiplicative process coincides exactly with a lognormal model, but a
      multiplicative-competitive process such as that which is embedded in the
      nonlinear deterministic model has a narrower distribution. Large sample sizes
      are, however, needed to uncover this departure from the lognormal. Biologically,
      at least two phases of the empiric IP should be told apart: lengthy IPs should be
      distinguished from short and median IPs. Lengthy IPs emphasize interaction
      (complexity) between the disease progression and the immunological defenses of
      the host. Simulated distributions involving process complexity closely fit
      selected cancer data sets. Process complexity of the host pathologic unfolding
      can actually be recognized and quantified.

PMID- 7730868
TI  - Sample size calculations for single group post-marketing cohort studies.
AB  - In pharmacoepidemiology, single group cohort is the most frequently proposed
      design to determine if the incidence rate of an adverse drug reaction among the
      exposed differs from a reference value. In many situations, the number of events
      expected in the cohort is too small to conduct sample size calculations based on
      the normal distribution. This paper proposes, for a single group cohort study,
      calculations and tables derived from the Poisson distribution. The results are
      based on a one-sided test with a 0.05 significance level and a power of 0.9 and
      0.8. Two parameters have to be specified a priori: the expected incidence of the
      event under the null hypothesis and the minimum risk ratio to be detected. The
      required sample size and the critical number of events to reject the null
      hypothesis are directly derived from the tables. Results show that the normal
      approximation may lead to an underestimation of the required sample size.

PMID- 7730869
TI  - Semantic ambiguity, the "non-" nosology and myocardial infarction.

PMID- 7730870
TI  - The association of waist/hip ratio with diabetes complications in an adult IDDM
      population.
AB  - Cross-sectional data from the Epidemiology of Diabetes Complications Study were
      used to examine the relationships between waist to hip circumference ratio (WHR)
      and the presence of diabetes complications in IDDM adults ages 18-45 years (N =
      586). Significantly higher WHRs were observed among both genders with
      proliferative retinopathy or peripheral vascular disease and only among males
      with either neuropathy or nephropathy compared to those free of these
      complications. Logistic regression to determine the strength of association
      between WHR and each complication demonstrated that although WHR was
      significantly related to each complication (except nephropathy among females),
      WHR was only independently related to neuropathy in males and PVD in females in
      the final model when hypertension, LDL- and HDL-cholesterol and fibrinogen were
      included. These findings suggest that WHR acts as a marker of risk for diabetes
      complications mainly through an influence on other complication risk factors.

PMID- 7730871
TI  - Construction of a surrogate variable for impotence in the Massachusetts Male
      Aging Study.
AB  - Uncollected data must be filled in after the fact in many epidemiological
      studies. We compared several methods for constructing a surrogate variable for
      erectile potency, based on responses to related questions, in the Massachusetts
      Male Aging Study (MMAS). Quadratic discriminant analysis performed best among the
      procedures tested, achieving high rates of correct classification in cross
      validation of training data and (according to posterior estimates) in
      classification of MMAS subjects. Two versions of the surrogate variable were
      constructed, one involving a discrete classification and the other involving a
      set of continuous probabilities. The two versions were used to investigate
      medical correlates of impotence in MMAS and produced similar results, although
      the continuous version appeared to provide higher statistical power. We conclude
      that construction of a surrogate variable is a viable and potentially beneficial
      option in epidemiological investigations.

PMID- 7730872
TI  - Casual blood pressure in a general Danish population. Relation to age, sex,
      weight, height, diabetes, serum lipids and consumption of coffee, tobacco and
      alcohol.
AB  - A population survey was conducted on 3608 randomly selected Danes aged 30, 40, 50
      and 60 years respectively. Of these, 3400 were not in medical treatment for
      arterial hypertension. The following parameters were investigated: sex, age,
      serum lipid levels (total cholesterol, HDL cholesterol, triglycerides), presence
      of diabetes mellitus, height, body mass index (BMI), and average daily
      consumption of coffee, tobacco and alcohol. Analysis with multiple linear
      regression showed that all variables with the exception of triglycerides, HDL
      cholesterol and height were significantly associated with systolic blood
      pressure. Likewise all factors except diabetes, triglycerides and height were
      significantly associated with diastolic blood pressure. Further analysis in which
      the effect of each parameter was corrected for by the effects of the remaining
      variables, demonstrated that apart from age and sex only BMI and high alcohol
      consumption were positively associated with differences in blood pressure greater
      than a few mmHg. However, the variation in both systolic and diastolic blood
      pressures was only partly accounted for by the parameters studied--in the
      covariates analysis R2 for systolic blood pressure was 0.28 and R2 for diastolic
      blood pressure was 0.30. In conclusion, this investigation demonstrated that
      blood pressure is relatively independent of other factors important in the
      development of cardiovascular disease. Of the above-mentioned factors with some
      influence on blood pressure only age, BMI and high alcohol consumption have
      potential clinical importance.

PMID- 7730873
TI  - Racial and marital status influences on 10 year survival from breast cancer.
AB  - The association of race and marital status with survival during a 10 year period
      after a breast cancer diagnosis is described. The data for this study were
      obtained from the Metropolitan Detroit Cancer Surveillance System, a participant
      in the National Cancer Institute's SEER program. The study sample was 10,778
      women (85.6% white and 14.4% black) diagnosed with incident invasive breast
      cancer between 1973 and 1978. Marital status was significantly associated with
      race, but had only a weak relationship with length of survival in a multivariate
      model predicting 10 year survival. However, race was strongly related to
      survival. African American women were significantly more likely than white women
      to die from breast cancer after controlling for age at diagnosis, marital status,
      tumor stage, histologic type, treatment status, and the interaction of age with
      stage. Ten years after being diagnosed with breast cancer, 38.2% of whites,
      compared with 33.3% of blacks were still living. These data confirm a body of
      literature which finds that blacks experience a shorter survival period following
      a cancer diagnosis than do whites. However, the relationship of marital status to
      cancer survival is still unclear and needs further study.

PMID- 7730874
TI  - The interrelationship between impaired glucose tolerance and other risk factors
      for cardiovascular disease: is it a predictor for cardiovascular disease?
AB  - Glucose intolerance and cardiovascular risk factors were assessed among 215
      subjects aged 27-86 years in Ho-long, Taiwan. An oral glucose tolerance test
      (OGTT) was normal in 107 subjects, impaired in 41 subjects, and abnormal in 67
      subjects (as noninsulin dependent diabetes mellitus, NIDDM). Body fatness, blood
      pressure, carbohydrate and lipid metabolic factors were examined. One-way ANCOVA
      was used to compare age- and/or BMI-adjusted differences among these groups. Male
      subjects with NIDDM and impaired glucose tolerance (IGT) had higher systolic
      (SBP) and diastolic (DBP) blood pressures, plasma insulin (fasting and 1-hour
      after OGTT), serum triglycerides (TG), heavier body weight, and larger BMI than
      normal. IGT subjects were also found to have higher TG, insulin (2-hour) and
      larger insulin area under curve (IAUC) after OGTT than NIDDM. In females,
      subjects with NIDDM had higher TG, insulin (fasting and 1-hour after OGTT), and
      larger IAUC than normal. Moreover, female IGT subjects were also found to have
      significantly higher SBP, DBP, insulin (1-and 2-hour after OGTT), and larger IAUC
      than both normal and NIDDM subjects. These results suggest that adverse
      cardiovascular risk factors are present not only in NIDDM subjects, but also in
      IGT subjects.

PMID- 7730875
TI  - Black women have smaller abdominal girths than white women of the same relative
      weight.
AB  - Anthropometric measurements were compared in 312 white and 242 black women (mean
      age 54) who were participants in the Charleston Heart Study. Body mass index
      (BMI) was greater in black women (27.8 kg/m2) than in white women (24.7 kg/m2) as
      were body circumferences. However, when the girth measurements were adjusted for
      BMI, some racial differences were reversed. Age, smoking and BMI-adjusted
      abdominal girth was smaller in the black women than in the white women (88.9 cm
      vs 92.2 cm). The ratio of abdomen to midarm circumference was larger in white
      women than black women (3.24 vs 3.09), and could be interpreted to indicate a
      less central fat pattern in the black women. This conclusion should be viewed
      with caution since circumference measurements, though often used in epidemiologic
      research, do not differentiate between subcutaneous fat and visceral fat.

PMID- 7730876
TI  - Predictors of coronary angiography in patients with idiopathic dilated
      cardiomyopathy: the Washington, DC Dilated Cardiomyopathy Study.
AB  - Although a number of clinical and demographic factors have been associated with
      the performance of angiography in cardiac patients, clinical studies of
      idiopathic dilated cardiomyopathy (DCM) have often excluded patients who have not
      undergone coronary angiography to rule out coronary artery disease (CAD). To
      examine the impact of this diagnostic criterion on population-based studies of
      idiopathic DCM, we examined characteristics of probable cases of DCM who did or
      did not have a recorded history of angiography. The cases (n = 129) were
      ascertained from five medical centers in the Washington, DC metropolitan area
      over the period 1 July 1990 through 29 February 1992. All of these cases had
      evidence of ventricular dilation and hypokinesis, with a left ventricular
      ejection fraction of less than 40%. Cases with a history of known CAD, congenital
      heart disease, valvular heart disease, or secondary cardiomyopathy were excluded.
      Sixty-two (48%) of the cases had a recorded history of angiography. Age,
      educational level, diabetes, alcohol use, insurance status, and type of hospital
      were significantly associated with angiography in bivariate analysis (p < 0.05).
      Diabetes and hypertension were inversely associated with history of angiography
      among black cases, and positively associated with angiography among whites. In
      logistic regression analysis, age was the strongest independent predictor of
      angiography (p < 0.025). The associations with educational attainment and alcohol
      use were of borderline significance (p < 0.10). Thus, in epidemiologic studies of
      idiopathic DCM, particularly in biracial populations, the exclusion of cases who
      have not undergone angiography may bias risk estimates and result in the
      underestimation of incidence and prevalence.

PMID- 7730877
TI  - Fibrinogen and fibrinolytic variables in relation to anthropometry, lipids and
      blood pressure. The Northern Sweden MONICA Study.
AB  - Fibrinolysis is dependent upon plasminogen activator (tPA) activity while high
      fibrinogen levels increase the risk of thromboembolic events. From a cross
      sectional population sample of 1558 men and women aged 25 to 64 years, plasma
      fibrinogen, tPA activity and plasminogen activator inhibitor-1 (PAI) activity
      were determined using specific assays. Associations with body mass index (BMI),
      waist-hip ratio (WHR), serum lipids and blood pressure were calculated with uni-
      and multivariate models where age and smoking were also introduced. In men age,
      truncal obesity, short height and low HDL cholesterol independently predicted
      fibrinogen (R2 0.20) while in women obesity per se, total cholesterol, systolic
      blood pressure, smoking and age were predictors (R2 0.29). tPA activity was
      negatively associated with BMI and serum triglyceride levels and positively with
      age in both sexes. In men diastolic blood pressure (R2 0.22) and in women WHR
      further independently predicted low fibrinolytic activity. HDL was associated
      with greater fibrinolysis in women (R2 0.15). Relationships with PAI-1 activity
      were essentially the reverse of tPA but stronger. Prospective interventional
      studies are needed to answer the question of causality.

PMID- 7730878
TI  - A randomized trial of a low fat high fibre diet in the recurrence of colorectal
      polyps. Toronto Polyp Prevention Group.
AB  - After polypectomy for adenomatous colorectal polyps, 201 persons were randomized
      to receive counselling on a diet low in fat (the lesser of 50 g/day or 20% of
      energy) and high in fibre (50 g/day) (LFHF), or to follow a normal western diet
      (ND), high in fat and low in fibre. After 12 months of counselling, fat
      consumption was about 25% of energy in the LFHF group and 33% in the ND group;
      fibre consumption was 35 g and 16 g respectively. After an average of two years
      of follow-up, an intention to treat analysis led to a ratio of cumulative
      incidence rates of 1.2 (95% CL 0.6-2.2) for recurrence of neoplastic polyps, a
      finding which suggests no significant difference between dietary groups over the
      period of observation. An exploratory analysis conducted among 142 persons with
      substantial diet counselling indicated a reduced risk of neoplastic polyp
      recurrence in women (RR = 0.5), associated with reduced concentrations of faecal
      bile acids while on the LFHF diet, but indicated an increased risk of recurrence
      in men (RR = 2.1), associated with increased faecal bile acids. Although a larger
      study would be needed to rule out the role of chance, these findings of gender
      specific associations between diet counselling and both faecal bile acid
      concentrations and recurrence of colorectal neoplasia are consistent with
      recently published evidence of differences between genders.

PMID- 7730879
TI  - An index of symptoms for infection with human immunodeficiency virus: reliability
      and validity.
AB  - The objective of this study was to evaluate the reliability and validity of a
      brief index to measure symptoms in individuals infected with human
      immunodeficiency virus (HIV). From an ambulatory clinic that specializes in the
      care of HIV-infected individuals at a university hospital in northeast Ohio, 148
      randomly selected outpatients (predominantly homosexual men) with a broad
      spectrum of HIV disease were enrolled in a prospective, cohort study. In standard
      interviews, patients rated the frequency of 36 symptoms related to HIV infection
      on an ordinal scale from zero (never) to three (daily); these interviews were
      repeated and outcomes determined every 3 months for one year. Clinical data were
      abstracted from the medical record with a standard chart review. Using specific
      criteria, 12 symptoms were selected for the HIV Symptom Index: fatigue, fevers,
      headache, imbalance, paresthesias, memory loss, cough, nausea, diarrhea, sadness,
      sleep disturbance, and skin problems. The HIV Symptom score (the sum of frequency
      ratings for the 12 symptoms) ranged from 0 to 31 with a mean of 9.4 (+/- SD 6.6).
      The test-retest reliability was high (intraclass correlation coefficient = 0.92)
      as was the internal consistency (Cronbach's alpha = 0.79). The validity of the
      index was established with three observations. (1) The HIV Symptom Index makes
      clinical sense and includes a representative spectrum of symptoms of infection.
      (2) Symptom Index scores were greater in patients with more advanced disease and
      in patients who were functionally impaired. (3) The Index was responsive to
      changes in health as the disease progressed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730880
TI  - Screening with total cholesterol: determining sensitivity and specificity of the
      National Cholesterol Education Program's guidelines from a population survey.
AB  - The objective of the study was to determine the sensitivity and specificity of
      the National Cholesterol Education Program (NCEP) guidelines in identifying at
      risk individuals for hypercholesterolemia, using population-based data from the
      Manitoba Heart Health Survey (MHHS). The MHHS surveyed a representative sample of
      adult residents of the province of Manitoba, Canada, aged 18-74 (n = 2792), 2212
      of whom underwent complete lipoprotein analyses: total cholesterol (TC), high
      density (HDL) and low-density (LDL) lipoprotein cholesterol, and triglycerides
      (TG) after overnight fasting. Following NCEP criteria for risk categories, 618
      individuals could be considered as "at risk" based on their HDL and/or LDL
      levels. However, if the NCEP algorithms were followed, i.e. initial screen for TC
      only, and determination of HDL and LDL for selected individuals with borderline
      and high TC, only 438 of the total "at risk" individuals would have been
      identified (sensitivity = 71%). 1203 of 1594 individuals with acceptable HDL and
      LDL levels were not considered "at risk" on screening (specificity = 76%). If "at
      risk" status was determined solely on LDL criteria, the NCEP guidelines result in
      a higher sensitivity (94%) and comparable specificity (76%). However, when only
      HDL criteria were used, the sensitivity and specificity declined to 38% and 63%
      respectively. Compared to a simulated screening study based on the Lipid Research
      Clinic data reported by Bush and Riedel (1991) the estimates of sensitivity from
      the MHHS were high. Current NCEP guidelines appear to balance optimally the
      sensitivity and specificity for selecting individuals based on TC levels for
      further complete lipoprotein analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730881
TI  - Does mood-congruence or causal search govern recall bias? A test of life event
      recall.
AB  - Recall bias has been hypothesized to occur as a function of mood congruence or
      causal-search related mechanisms. This study tested whether either mechanism
      related to recall of stressful life events over a year. Respondents consisted of
      136 cases suffering from chronic facial pain and 131 acquaintance controls. After
      reporting life events for 1 year at monthly intervals, respondents attempted to
      recall these same events at year-end. Mood and likelihood of engaging in causal
      search were also ascertained at year-end. Results showed no effect of mood
      congruence or causal search on recall of event occurrence. However, mood did
      influence subjective appraisal of those events that were recalled. In addition, a
      significant mood-related memory deficit was detected. Findings indicate that mood
      related memory deficit may reduce effect sizes artifactually. Furthermore, when
      assessing effects of recall bias, recall of event occurrence must be considered
      separately from subjective appraisal of event characteristics.

PMID- 7730882
TI  - Further on the association between retarded foetal growth and adult
      cardiovascular disease. Could low intake or marine diets be a common cause?

PMID- 7730883
TI  - Visual presentation of analysis of test performance.

PMID- 7730884
TI  - Investigator bias and interviewer bias: the problem of reporting systematic error
      in epidemiology.
AB  - Epidemiologists recognize that systematic errors in the design or conduct of a
      study may bias the results. Information on the exposure of interest may be
      especially prone to misclassification. Even information that has been well
      documented may be reported incorrectly. Study subjects may have difficulty
      recalling past exposures or behaviors, or may provide responses based on wishful
      thinking. The nature and importance of these biases is not always fully
      considered by investigators in their data analysis and in their investigation.
      This paper reviews the most common type of biases and cites examples of how the
      responses of subjects substantially affect study results.

PMID- 7730885
TI  - Vitamin supplementation and reduced risk of basal cell carcinoma.
AB  - A clinic-based case-control study was conducted to determine the association
      between vitamin supplement use and risk of basal cell carcinoma (BCC) of the
      skin. The subjects were 131 patients with histopathologically confirmed primary
      BCC and 200 cancer-free controls with non-premalignant skin disorders. Use of any
      vitamins (mainly multivitamins and vitamins A, C, and E) was associated with
      reduced risk of BCC. After controlling for age, sex, cigarette smoking, number of
      lifetime severe sunburns, and skin actinic elastosis, regular vitamin
      supplementation was associated with a significantly reduced risk of BCC (odds
      ratio (OR) = 0.3; 95% confidence interval (CI) = 0.2-0.06). The ORs decreased as
      the regularity (p < 0.001) and daily doses of supplement used increased,
      especially for vitamins A (p < 0.005) and E (p < 0.005). Vitamin supplementation
      was not associated with alterations in cellular DNA repair. These results,
      however, cannot be considered conclusive because of the relatively low
      participation rates (131/830 for cases and 200/1406 for controls) due to the
      requirement of blood donation and more rigorous studies are needed to clarify the
      effect of supplemental vitamins, particularly of vitamins A and E, on the risk of
      BCC of the skin.

PMID- 7730886
TI  - Sex and ethnic group differences in fat distribution in young United Kingdom
      South Asians and Europids.
AB  - South Asians (Asians) have a high prevalence of non-insulin-dependent diabetes
      (NIDDM) and a high incidence of ischaemic heart disease (IHD). To investigate
      whether this predisposition can be detected in young adult life, metabolic risk
      factors for these diseases were compared in U.K. Europid and Asian students.
      Among the 80 Europid and 80 Asian students aged between 20 and 23 years and well
      matched for body mass index (BMI), Asians were found to be relatively
      hyperglycaemic [5.1 (5.0-5.2) vs 4.6 (95% CI: 4.5-4.7) mmol/l] and
      hypercholesterolaemic [5.3(5.2-5.4) vs 4.9 (4.8-5.0) mmol/l] and to have a higher
      waist/hip and subscapular/triceps ratio. The waist/hip ratio was found to be a
      better predictor of glucose and cholesterol than calliper measurements in both
      ethnic groups although the subscapular/triceps ratio was independently related to
      both glucose and cholesterol. Predictors of both IHD and NIDDM are present at an
      early age in U.K. Asians.

PMID- 7730887
TI  - Incidence rate of falls in an aged population in northern Finland.
AB  - The total elderly population aged 70 years or over living in five rural districts
      in northern Finland, 1159 persons in all, were monitored by 'phone prospectively
      for 1 year, all falls being recorded separately for those living at home and in
      institutions. Of those living at home, 30% fell at least once during the year,
      19% just once, this proportion not depending on age or sex. The home-dwelling men
      and women experienced 368/1000 PY and 611/1000 PY falls, respectively, the
      incidences tending to increase with advancing age. The men in institutions
      experienced 2021 falls/1000 PY and the women 1423/1000 PY, without clear age
      dependence. The home-dwelling women had a greater risk of falling repeatedly than
      the men, but the sex differences disappeared with advancing age. The falls among
      home-dwellers were concentrated in the day-time, whereas no variation with time
      of day was found in the institutions. Falls are common in the elderly, but their
      incidence and certain characteristics differ considerably between the home
      dwellers and those living in institutions.

PMID- 7730888
TI  - The efficacy of back schools: a review of randomized clinical trials.
AB  - The purpose of this study was to assess the efficacy of back school programmes
      for low-back pain. Data sources comprised computer-aided search of published
      randomized clinical trials and assessment of the methods of the studies. 21
      papers reporting on 16 randomized clinical trials evaluating a back school
      programme were selected for the study. Data extraction included a score for
      quality of the methods, based on four categories: study population,
      interventions, effect measurement and data presentation and analysis; and the
      conclusion of the author(s) with regard to the efficacy of the back school
      programme. Only two studies scored more than 50 points (maximum = 100 points)
      indicating the overall poor quality of the methods. Seven studies indicated that
      the back school programme was more effective than the reference treatment and
      seven reported it to be no better or worse than the reference treatment. In two
      studies the authors refrained from drawing a conclusion. The studies reporting
      positive results showed higher methods scores (4/7 positive vs 0/7 negative
      scored > or = 45 points). Reported benefits of back schools were usually of short
      duration only. There are major flaws in the design of most studies. The best
      studies indicated that back schools may be effective in occupational settings in
      acute, recurrent or chronic conditions. The most promising type of interventions
      were (modifications of) the "Swedish back school" and were quite intensive (a 3
      to 5-week stay in a specialized centre). Future research efforts should focus on
      the identification of patients who would benefit most from back schools. In
      addition, more attention should be paid to the cost-effectiveness of back
      schools.

PMID- 7730889
TI  - The sickness impact profile: SIP68, a short generic version. First evaluation of
      the reliability and reproducibility.
AB  - In previous research a short version of the Sickness Impact Profile (SIP136) was
      developed, containing 68 items. This SIP68 is intended as a short generic
      alternative to the original SIP. High reliability of the SIP68 was reported when
      it was extracted from the SIP136. This paper is a report on the first reliability
      testing of the SIP68 administered as an independent instrument without the
      context of the SIP136. To establish the test-retest reliability and the internal
      consistency of the new instrument, 51 patients of an outpatient department of
      rheumatology completed the SIP68 twice, with an interval of 48 hours. To compare
      the performance of the independent SIP68 with the SIP68 extracted from the
      SIP136, the SIP136 also was completed two times by the same 51 respondents. Test
      retest reliability for both administration types was assessed by means of the
      intraclass correlation coefficient and the Jaccard's similarity ratio. Internal
      consistency was assessed by means of Cronbach's alpha. The reliability appears to
      be high in both the independent SIP68 as well as the extracted SIP68. Moreover,
      the reliability of the independent SIP68 appears to be as high as for the SIP136.
      These findings were very encouraging, indicating that the SIP68 may very well
      serve as a generic alternative to the SIP136.

PMID- 7730890
TI  - The effect of exposure variance and exposure measurement error on study sample
      size: implications for the design of epidemiologic studies.
AB  - A small variability of exposure in a population, for example small variance in
      nutrient intake, limits the power of an epidemiologic study. McKeown-Eyssen and
      Thomas (J Chron Dis 1985; 38:559-568) have shown that by selecting a population
      with larger exposure variance vs one with smaller variance, the study sample size
      can be reduced by a factor equal to the ratio of the smaller to larger variance.
      The authors show that this benefit may be even greater for exposures measured
      with error. When there is measurement error, the sample size requirements are
      greatly increased. However, the proportional reduction in sample size from
      selecting a population with larger variance may be even greater when there is
      error than when there is not. Under certain assumptions, the validity of the
      exposure (correlation coefficient of the mismeasured exposure with the true
      exposure) is enhanced in the population with larger exposure variance, which
      provides the additional sample size benefit. Simple equations are presented that
      demonstrate quantitatively the substantial benefit of selecting a population with
      larger exposure variance when there is moderate or large measurement error. For
      example, selecting a population with a 30% greater standard deviation of exposure
      could reduce sample size requirements by 41% when the exposure is perfectly
      measured, but when the exposure is poorly measured with a validity coefficient of
      0.6, the savings could be 56% if a population with 30% greater standard deviation
      of exposure could be studied. Applications of these results as well as the
      limitations of the assumptions are discussed.

PMID- 7730891
TI  - Clinically useful measures of effect in binary analyses of randomized trials.
AB  - The results of a randomized clinical trial can be reported using relative and/or
      absolute estimators of treatment effect. These various measures convey different
      information, and the choice can influence the physician's appreciation of the
      size of treatment effect and, subsequently, treatment decisions. We compare the
      estimators with respect to the clinically relevant information conveyed to
      physicians, and identify which clinical questions can and cannot be answered
      directly by each. We also identify opportunities for misinterpretation when one
      estimator is substituted for another, or when an estimator is mislabeled.
      Clinically important questions are addressed most directly by reporting both
      relative and absolute effects using relative risk and its complement, relative
      risk reduction, and risk difference and its reciprocal, number needed to treat.
      This is true of estimates of treatment effect derived from a single trial and
      also from meta-analysis of a group of trials. Because the control group's risk
      affects the numerical value of the odds ratio, the odds ratio cannot substitute
      for the risk ratio in conveying clinically important information to physicians.
      This is especially important when large treatment effects are shown in trials
      carried out in populations at high baseline risk.

PMID- 7730892
TI  - A summated score for the medication appropriateness index: development and
      assessment of clinimetric properties including content validity.
AB  - Inappropriate medication prescribing is an important problem in the elderly, but
      is difficult to measure. As part of a randomized controlled trial to evaluate the
      effectiveness of a pharmacist intervention among elderly veterans using many
      medications, we developed the Medication Appropriateness Index (MAI), which uses
      implicit criteria to measure elements of appropriate prescribing. This paper
      describes the development and validation of a weighting scheme used to produce a
      single summated MAI score per medication. Using this weighting scheme, two
      clinical pharmacists rated 105 medications prescribed to 10 elderly veterans from
      a general medicine clinic. The summated score demonstrated acceptable reliability
      (intraclass correlation co-efficient = 0.74). In addition, the summated MAI
      adequately reflected the putative heterogeneity in prescribing appropriateness
      among 1644 medications prescribed to 208 elderly veterans in the same general
      medicine clinic. These data support the content validity of the summated MAI. The
      MAI appears to be a relatively reliable, valid measure of prescribing
      appropriateness and may be useful for research studies, quality improvement
      programs, and patient care.

PMID- 7730893
TI  - Inter-observer variability among pathologists' evaluation of malignant melanoma:
      effects upon an analytic study.
AB  - This study examined whether inter-observer variability in rating tumor
      characteristics affected results of an investigation of surveillance bias and
      malignant melanoma at the Lawrence Livermore National Laboratory. The 20 cases
      from the Laboratory and their 36 non-Laboratory controls belonged to the same pre
      paid health plan and were diagnosed with melanoma between 1970 and 1984. Tumors
      were independently and then jointly rated by three dermatopathologists blind to
      the subjects' Laboratory status. The mean difference between the reviewers and
      the consensus reading for tumor thickness was small, ranging from -0.06 mm (95%
      confidence interval [CI]--0.12, 0.00) to 0.00 mm (95% CI--0.07, 0.07). Agreement
      was much lower for histologic type (kappa = 0.48, 95% CI 0.37, 0.58). Because the
      inter-observer variability, the study's hypothesis was rejected by analyses based
      on data from the consensus reading and two reviewers, but not on data from the
      third reviewer. These findings suggest that epidemiologists using data subject to
      inter-observer variability may want to employ consensus instead of individual
      ratings.

PMID- 7730894
TI  - Detecting survival effects of socioeconomic status: problems in the use of
      aggregate measures.
AB  - Direct measures of SES are seldom included in medical records or large databases
      on disease incidence or survival, forcing researchers to infer the SES
      characteristics of individuals from aggregate data (e.g. census tract-level
      income, education, etc.). This paper assesses the degree of error that results
      from such inference and the impact this error may have on reported relationships
      between SES and survival. The authors obtained both individual and census tract
      level data on 536 persons diagnosed with cancer between 1980 and 1982 and
      monitored their survival through 1992. Pearson correlations between individual
      level and census tract-level SES variables ranged between 0.2 and 0.4.
      Statistically significant relationships between SES and survival were observed in
      the models based on individual-level but not census tract-level SES data. The
      authors computed the degree to which inference of individual-level from census
      tract-level SES reduces estimates of risk ratios across SES. It appears likely
      that much larger numbers of observations than have been used in published studies
      will be needed to better understand the relationship of SES to survival and other
      disease outcomes.

PMID- 7730895
TI  - White blood cell count and hypertension incidence. The NHANES I Epidemiologic
      Follow-up Study.
AB  - To test the hypothesis that elevated white blood cell count (WBC) is associated
      with increased incidence of essential hypertension, data from the NHANES I
      Epidemiologic Follow-up Study (NHEFS) were analyzed. Incidence of hypertension
      was determined in a cohort of 5782 white and 674 black persons with complete data
      who were normotensive at baseline. There was a statistically significant increase
      of about 50% in risk of hypertension over approximately 10 years' follow-up in
      white men aged 25-74 years with WBC > 8600 compared to men with WBC < 6200
      cells/mm3. The association was independent of other risk variables. In white
      women, an association of high WBC with increased age-adjusted risk of
      hypertension was seen only at ages 45-64 and 65-74 years. The association was
      diminished and no longer significant after controlling for multiple risk
      variables. Data for black women suggested an increased risk among women with
      higher WBC compared to those with lower WBC at ages 65-74 after controlling other
      risk variables (p = 0.0001). No positive association was seen in black men. Thus,
      data from NHEFS confirm the previously reported association of higher WBC with
      increased incidence of hypertension in white men, and possibly older white and
      black women. Given the lack of a compelling biological explanation, further
      studies of this association are needed, especially in women and blacks.

PMID- 7730896
TI  - Reproducibility of carotid vessel wall thickness measurements. The Rotterdam
      Study.
AB  - We studied the reproducibility of measurement of ultrasonographically assessed
      common carotid intima-media thickness and assessed whether measurement error of
      intima-media thickness occurred randomly or was associated with potential
      determinants of atherosclerosis. Eighty participants of the Rotterdam Study
      underwent a second ultrasound scan of both carotid arteries within 3 months of
      the first scan. The replicate measurements involved the posterior intima-media
      thickness of the distal common carotid artery. Mean differences (SD) in intima
      media thickness of the right common carotid artery between paired measurements of
      sonographers, readers and visits were -0.004 mm (0.10), 0.066 mm (0.07), and 
      0.013 mm (0.13), respectively. Similar results were obtained for the left common
      carotid artery. Measurement error of intima-media thickness, i.e. the absolute
      difference in measurements between two subsequent visits, increased significantly
      with increasing common carotid intima-media thickness. This association
      disappeared after logarithmical transformation of the intima-media thickness
      data. Age, sex, smoking, body mass index, serum lipids, fibrinogen, and systolic
      and diastolic blood pressure were not significantly associated with the
      measurement error of intima-media thickness. Our findings indicate that
      measurements of common carotid intima-media thickness are highly reproducible.
      Measurement error of intima-media thickness is small and appears to be
      proportional with the level of intima-media thickness and is not significantly
      associated with most risk factors for atherosclerotic vessel wall disease.

PMID- 7730897
TI  - Defining the impact of prevention and improved management upon stroke mortality.
AB  - Stroke mortality in developed countries has significantly declined. The purpose
      of this study is to demonstrate a cross-sectional model of aging and mortality
      with which the impact of prevention and improved management upon stroke mortality
      can be quantified. Stroke mortality in the U.S. between 1951 and 1988 among
      whites aged 20-85 years was analyzed using the Strehler-Mildvan modification of
      the Gompertz relationship between aging and mortality. Between 1951 and 1988,
      environmental (non-genetic) influences upon U.S. stroke mortality declined 16.4%
      among white men and 22.16% among white women. Cross-sectional mortality analysis
      may be necessary to eliminate the effect of differential survival bias inherent
      in cohort mortality analysis.

PMID- 7730899
TI  - When there's "no cure".

PMID- 7730898
TI  - The correlation of epidemiological variables.
AB  - Data from a sizable hospital-based, case-control study from 1985 to 1990
      permitted us to examine the correlation of variables by degree of
      interrelationship. The variables examined relative to their confounding
      interrelationships include smoking; consumption of alcohol, coffee, meat,
      vegetables, and fruits; body mass index; education, and age. The variables with
      the broadest impact on others are age and education. While the association among
      these variables is generally known, the degree of association made possible by
      our large database is generally not fully appreciated and is of obvious
      significance when data are adjusted for one other variable. In some instances,
      the intercorrelation among different variables is relatively complicated. For
      instance, cigarette smoking correlates positively with meat consumption and
      negatively with intake of fruits and vegetables, which, in turn, correlates with
      alcohol intake. These interrelationships need to be clearly understood before
      interpreting epidemiologic data for causation. In general, the correlations are
      similar for men and women. This study of correlation of variables, some expected
      and some unexpected, should be of value as a source to epidemiologists and
      provide a useful base.

PMID- 7730900
TI  - Vascular dementia--the legacy of Thomas Willis.

PMID- 7730901
TI  - Design options of prospective epidemiologic studies.

PMID- 7730902
TI  - Access to therapy in the Multicenter AIDS Cohort Study, 1989-1992.
AB  - The study aims were (i) to describe secular trends in the utilization of
      antiretrovirals, antivirals, Pneumocystis carinii pneumonia (PCP) prophylaxis,
      and antifungal prophylaxis and (ii) to determine whether factors such as clinical
      status, health services utilization, insurance status, income, education and race
      were associated with access to therapy. Data on utilization of therapy, health
      services utilization, income and insurance status were collected semiannually
      from October 1990 through March 1992 from 1415 homosexual/bisexual HIV-1
      seropositive men in the Multicenter AIDS Cohort Study (MACS). Prevalence of
      therapy use according to level of immunosuppression was determined at each study
      visit. Clinical AIDS was defined using the 1987 CDC definition. Factors
      associated with use of antiretroviral therapy and PCP prophylaxis were assessed
      using multiple logistic regression with robust variance techniques to adjust
      variance estimates and significance levels for within-person correlations of drug
      use over time. Prevalence of zidovudine use remained relatively constant
      throughout the study period. In contrast, use of didanosine (21-34%), acyclovir
      (23-34%) and dideoxycytidine (zalcitabine) (8-25%) increased in participants with
      clinical AIDS. Similar trends were seen for combination antiretroviral therapy,
      trimethoprim-sulfamethoxazole, dapsone, ketoconazole and fluconazole. However,
      reported use of aerosolized pentamidine fell. After adjusting for CD4+ lymphocyte
      count and HIV-1 symptoms, previous HIV-related hospitalization (OR = 1.52; 95% CI
      = 1.22-1.91), outpatient visit (OR = 2.83; 95% CI = 2.12-3.78), having insurance
      (OR = 1.32; 95% CI = 1.01-1.75), college education (OR = 1.42; 95% CI = 1.13
      1.80) and white race (OR = 1.58; 95% CI = 1.21-2.07) were all associated with
      being on antiretroviral therapy in persons without clinical AIDS. In persons with
      clinical AIDS, having insurance (OR = 2.89; 95% CI = 1.04-8.02) and a previous
      outpatient visit (OR = 11.69; 95% CI = 1.77-77.30) were the significant
      variables. Factors significantly associated with being on PCP prophylaxis in
      multivariate models were previous hospitalization, previous outpatient visit, and
      college education (for subjects without clinical AIDS.

PMID- 7730903
TI  - The low risk cardiac patient: an opportunity for cost containment.
AB  - The pressure to maintain high standards in the face of diminished medical funding
      has promoted a search for a low risk group of patients seen in cardiac practice
      in whom diagnostic and therapeutic technologies can be kept to a minimum. This
      study reports experience in a single cardiology practice in which all patients
      had a history taken, a clinical examination performed, and most had an
      electrocardiogram. Thereafter investigation and treatment was tailored to the
      individual patient's need. A retrospective study of 113 patients revealed that 93
      (82%) had high risk characteristics prior to their death: cardiac failure;
      unstable coronary heart disease; clinical or laboratory evidence of poor systolic
      function of the left ventricle or inoperable coronary artery disease; elective
      major surgery; evidence of poor prognosis due to non-cardiac disease. In
      contrast, only 124 (21%) of 588 consecutive patients seen in consultation had
      high risk characteristics. The prevalence adjusted mortality ratio of high to low
      risk cases was 17.4/1 and in one third of cases, high risk status was less than 6
      months duration. In a prospective study, 144 cases were classified at high risk
      and 373 at low risk. Three year survival rates were 74 and 91% respectively (p <
      0.0001). 46 (12.3%) of the 373 patients initially at low risk subsequently
      developed clinical features which permanently placed them in the high risk
      category. The 3 year survival in the low to high risk converters was 47% compared
      with 97% survival in those remaining at low risk throughout the period of
      observation (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730904
TI  - Glutathione and morbidity in a community-based sample of elderly.
AB  - This study examined the association of blood glutathione level, a potential
      marker of physiological/functional aging, with a number of
      biomedical/psychological traits in a subgroup (N = 33) of a representative sample
      of community-based elderly. Higher glutathione levels were associated with fewer
      number of illnesses (p < 0.05), higher levels of self-rated health (p < 0.01),
      lower cholesterol (p < 0.05), lower body mass index, and lower blood pressures.
      Subjects with diagnoses of arthritis, diabetes, or heart disease (as assessed by
      physicians) had at least marginally significant lower glutathione levels than
      those who were disease free. Glutathione, together with age and a measure of
      suppressed anger, accounted for 39% of the variance of an index of morbidity.
      Glutathione, by itself, accounted for 24% of the variance. To our knowledge, this
      is the first evidence of an association of higher glutathione levels with higher
      levels of physical health in a sample of community-based elderly. Further studies
      in large samples are needed to investigate glutathione as a potential overall
      health risk factor for morbidity among the elderly.

PMID- 7730905
TI  - Using administrative data to describe casemix: a comparison with the medical
      record.
AB  - We compared the coding of comorbid conditions in an administrative database to
      that found in medical records for 485 men who had undergone a prostatectomy. Only
      a few specific conditions showed good agreement between charts and claims. Most
      showed poor agreement and appeared more frequently in the chart. A comorbidity
      index calculated from each of these sources was used to explore the differences
      in mortality for patients who had undergone transurethral vs open prostatectomy.
      The claims-based comorbidity index most often underestimated the index from the
      chart. Proportional hazards analysis showed that models including either
      comorbidity index were better than those without an index and models with
      information from both indices were best. No analysis eliminated the effect of
      type of prostatectomy on long-term mortality. Claims-based measures of
      comorbidity tend to underrepresent some conditions but may be an acceptable first
      step in controlling for differences across patient populations.

PMID- 7730906
TI  - Data monitoring in clinical trials: the case for stochastic curtailment.
AB  - Interim analyses have become an essential part of the monitoring process of
      clinical trials. Stochastic curtailment has been used in such analyses. This
      procedure allows for calculation of the probability of rejecting the null
      hypothesis at the end of a trial given the current data and assuming the null or
      an alternative hypothesis for the remainder of the trial. Such information can be
      used to decide whether a trial should continue or be stopped early due to either
      treatment benefit or harm or because of lack of power to show an effect. Using
      stochastic curtailment, stopping rules for one- or two-sided test trials can be
      easily visualized by constructing boundaries based on the null and alternative
      hypotheses. Interim Z test statistics falling above or below these boundaries can
      aid in interim monitoring decisions. Methods for constructing boundaries,
      expected trial times and examples of clinical trials in cardiovascular and vision
      research where stochastic curtailment was used are presented.

PMID- 7730907
TI  - Correcting respiratory rate for the presence of fever.
AB  - This study defines what degree of respiratory rate (RR) elevation can be
      attributed to fever using a double blind randomized pre- and post-acetaminophen
      comparison of vital signs of febrile children presenting to an outpatient clinic.
      Inclusion criteria were aged between 6 weeks and 24 months, fever between 38.5
      and 40.1 degrees C, no serious illness such as sepsis, and no recent receipt of
      antipyretics or antibiotics. RRs counted over 1 min and rectal temperatures were
      recorded by a trained observer before, and 1 and 1.5 hours (hr) after receipt of
      10-15 mg/kg/dose of either acetaminophen (A) or placebo (P). Randomization
      produced groups A (n = 54), and P (n = 50) with similar mean age (12.3 vs 12.8
      mo.), gender distribution (57 vs 54% female), baseline temperature (39.1 vs 39.1
      degrees C), baseline RR (44 vs 45), and hours of fever prior to visit (42 vs 37
      hr). The most common diagnoses were otitis media (49%), viral syndrome (18%),
      upper respiratory infection (16%) or gastroenteritis (7%). The mean temperature
      decrement of group A was 0.4 degrees C at 1 hr and 0.9 degrees C at 1.5 hr
      compared to slight increases in fever of 0.3 degrees C at 1 hr and 1.5 hr in
      group P. Significant decreases in RR occurred in group A compared to group P at 1
      hr (7.0 vs 1.9, p = 0.009) and 1.5 hr (10.8 vs 4.0, p < 0.01).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7730908
TI  - Trends in coded causes of death following definite myocardial infarction and the
      role of competing risks: the Minnesota Heart Survey (MHS).
AB  - We investigated possible differences over time in underlying causes of death
      among validated definite myocardial infarction cases who were discharged
      following an index hospitalization in 1970, 1980, and 1985 in the Twin Cities,
      MN. No changes were observed in underlying causes of death assigned to patients
      who died prior to discharge in the 3 years. Among in-hospital survivors of
      definite MI, however, age-adjusted rates of death from non-cardiovascular causes
      more than doubled between 1970 and 1985 (P < 0.01). More specifically, mortality
      rates for diabetes mellitus increased significantly from 1970 to 1985 (P < 0.05),
      while those for neoplasms and diseases of the respiratory system increased non
      significantly. Whether these data are the result of artifactual changes in cause
      of death assignment or real changes in disease severity and comorbidity, these
      trends in long-term death following acute MI may have had a modest impact on
      reported community-wide coronary heart disease mortality rates.

PMID- 7730909
TI  - The Mini-Mental State Examination score and the clinical diagnosis of dementia.
AB  - To set a working cutoff score for the referral to diagnostic examination, we
      evaluated 150 consecutive patients with complaints potentially related to
      dementia, using the Mini-Mental State Examination (MMSE). All patients were later
      given a complete, standardized work-up and diagnosis as part of our Alzheimer's
      Disease Patient Registry protocol. Dementia diagnosis was made, consistent with
      accepted criteria, by consensus of the physicians and psychologist. Diagnosis was
      reaffirmed after 1-year follow-up exam; 133 of the 150 original patients
      completed follow-up (80 dementia, 53 no dementia). We evaluated the initial MMSE
      score compared with the follow-up diagnosis. Sensitivity, specificity, and
      predictive values were calculated for MMSE scores ranging from 22 through 29. The
      conventional cutoff score of < 24 shows a sensitivity of 0.63 and a specificity
      of 0.96; sensitivity increased at higher cutoff scores. Multivariate analysis
      showed that educational level added significant prediction only at scores of > or
      = 27. We conclude that an MMSE score of 26 or 27 should be used as a cutoff score
      in symptomatic populations with similar educational and socioeconomic backgrounds
      when the goal is to miss few true cases. Population surveys where the expected
      prevalence is low may require a different cutoff score to indicate the need for
      further diagnostic evaluation.

PMID- 7730910
TI  - Diagnostic certainty and potential for misclassification in exocrine pancreatic
      cancer. PANKRAS I Project Investigations.
AB  - Whereas over the last decade epidemiologic studies on exocrine pancreatic cancer
      (EPC) continued to show a remarkable heterogeneity in diagnostic criteria applied
      to define caseness, the actual magnitude and consequences of misclassification
      remain largely unexplored. The objectives were: (1) to estimate the degree of
      certainty with which cases of EPC are diagnosed in the two participating
      hospitals (to this end a diagnostic certainty classification (DCC) was developed;
      (2) to test whether characteristics of cases differed by degree of diagnostic
      certainty; and (3) to assess what influence different definitions of case might
      have on risk estimates for tobacco and alcohol. All cases with a discharge
      diagnosis of EPC who attended at the Hospital del Mar between 1980-90 and at the
      Hospital Son Dureta between 1983-90 were identified through their respective
      tumor registries, and their clinical records were reviewed. Only 52% of 140 cases
      were classified in the group with a higher probability of EPC (group H).
      Diagnostic certainty appeared somewhat greater among women (age-adjusted odds
      ratio [ORa] 1.60, p = 0.18). Group H showed a higher proportion of cases with an
      interval from first symptom to diagnosis < or = 1 month (ORa = 2.38, p < 0.05)
      and the proportion of adenocarcinomas was slightly higher than in less certain
      cases (group L) (p = 0.051). A radical treatment was exclusively attempted in
      group H (p < 0.001). DCC cut-off points had a significant effect on the
      proportion of smokers and of alcohol drinkers, as well as on the percent of cases
      with pathological (cytohistological) confirmation. The proportion of cases
      unlikely to be of pancreatic origin in spite of having pathological confirmation
      was high enough to cause significant misclassification bias. Because past
      exposure to certain risk factors may differ among cases with different diagnostic
      certainty, we suggest to initially include in the case group patients who in
      spite of lacking pathological confirmation have strong clinical evidence
      supporting the diagnosis of EPC; subsequently, risk estimates should be computed
      across strata of diagnostic certainty to assess whether heterogeneity exists. In
      exocrine pancreatic cancer the impact of misclassification of disease status upon
      etiologic and prognostic estimates deserves at least as much attention as
      misclassification of exposure.

PMID- 7730911
TI  - Bias in studies of electromagnetic fields.

PMID- 7730912
TI  - Serum total cholesterol and mortality in a Japanese population.
AB  - Although the relation between serum total cholesterol and coronary heart disease
      is well established, the relation with mortality from non-coronary disease is
      controversial. Inverse relations of serum cholesterol with hemorrhagic stroke and
      cancer have stimulated the examination of cholesterol-non-coronary mortality
      associations. The population surveyed is 12,187 men and women aged 40-69 years
      living in Yao City, a suburb of Osaka, who undertook baseline examinations
      between 1975 and 1984 and had no history of stroke and coronary heart disease at
      baseline. The subjects were followed on average 8.9 years until the end of 1988
      using systematic mortality surveillance. During the follow-up, there were 343
      deaths, comprising 170 cancer deaths (International Classification of Death 9th
      edition: ICD-9, 140-239), 21 coronary heart disease deaths (ICD-9, 410-414), 67
      other cardiovascular deaths (ICD-9, 390-458 excluding 410-414), and 85 non
      cardiovascular, non-cancer deaths. There was a significant inverse association of
      serum cholesterol with total and cancer mortality for men, and no significant
      association for women. The cholesterol-disease association, although not
      significant, was positive for coronary heart disease and other cardiovascular
      disease deaths, and inverse for non-cardiovascular, non-cancer deaths in both
      sexes. The inverse association of serum cholesterol with total and cancer
      mortality for men remained significant after controlling for age, job
      classification, hypertension category, usual alcohol intake, cigarette smoking,
      and relative weight index.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730913
TI  - Case-control studies: matched controls or all available controls?
AB  - In order to realize the variation in the estimate of the odds ratio from case
      control studies, results from individually matched sampling were compared with
      those from the analysis based on a large number of controls. The subjects were
      selected from those who visited Aichi Cancer Center Hospital from 1988 to 1990.
      Cases consisted of 251 male lung cancer patients aged 40-79 years. Age and year
      of visit matched controls were sampled independently 100 times and 5000 times
      from non-cancer male outpatients (cases to controls ratio: 1:1, 1:2, 1:3, and
      1:4). As unmatched controls, all male non-cancer outpatients aged 40-79 years
      (4100 patients) were used. The smoking habit was adopted as an exposure variable.
      As logically expected, analysis based on 4100 male controls gave a steadier
      estimate than the matched analyses examined here, indicating that a matched
      sampling is not recommended when a large number of controls are available.

PMID- 7730914
TI  - Accuracy of self-report for stomach cancer screening.
AB  - Limited evidence is available regarding the accuracy of recall for cancer
      screenings. We compared the self-report of stomach cancer screening with medical
      records in 337 residents of a rural town in northeastern Japan, who were eligible
      for annual screening offered by the town. Frequencies of attendance within the
      last 5 years were asked in a self-administered questionnaire, and determined from
      the records of the organization conducting the screening. When the frequencies
      were dichotomized as ever/never screened within 5 years, the self-report agreed
      substantially with medical records, but tended to overestimate the actual
      attendance (kappa = 0.68, sensitivity = 100%, specificity = 75.6%). Past history
      of gastroduodenal diseases and family history of stomach cancer were associated
      with the overreport. Although the population studied was highly selective (rural
      Japanese volunteers), review of the previous studies on mammography and Pap smear
      also showed that self-reports tended to be exaggerated. Self-report of cancer
      screening should be regarded as an overestimated indicator of its true
      prevalence.

PMID- 7730915
TI  - Assessing the effect of time-varying covariates in cross-sectional studies.
AB  - In cross-sectional studies exposure and disease status of individuals are
      assessed at the same point in time, but sometimes information on prior exposure
      status is also gathered. Under such circumstances one approach to assessing the
      relationship between disease and exposure is using linear or logistic regression
      analysis, adjusting for exposure status at different points in time. It is shown
      that estimates for the effect of exposure at a certain point in time, adjusted
      for exposure at another point in time, are obtained from comparisons between
      groups with different patterns of exposure. Careful interpretation of the
      resulting estimates is necessary, taking into account a detailed consideration of
      possible exposure patterns. In addition, if changes in exposure are caused by the
      occurrence of the disease, then adjusting for multiple measurements of exposure
      can give misleading results. A regression analysis on dummy variables describing
      possible patterns of changes in exposure is proposed as an alternative approach.
      This approach facilitates interpretation of the resulting estimates. Furthermore,
      it can serve as a diagnostic tool to check for disease related changes in
      exposure. For this case transferring exposure change rates of healthy subjects to
      diseased subjects is suggested as an ad hoc method for assessing the hypothetical
      current relationship between exposure and disease.

PMID- 7730916
TI  - Presentation: The risk of lung cancer in nonsmokers in the United States and its
      reported association with environmental tobacco smoke.
AB  - Is environmental tobacco smoke (ETS) causally related to lung cancer? In this
      study, 29 case-control and three cohort studies involving exposed and unexposed
      female smokers (as defined herein, an exposed individual is a never-smoker
      married to a smoker and an unexposed individual is a never-smoker married to a
      never-smoker) and nine case-control and two cohort studies involving exposed and
      unexposed male smokers, in which presence or absence of lung cancer is the
      specified outcome, are reviewed. It is pointed out that any attempt to make
      inferences toward such a causal relationship must account for the fundamental
      differences in these studies, which took place on three continents over 15 years
      and involved many differences in individual study design as well as in study
      subjects. Since this has largely not been done, the only conclusion that sensibly
      can be drawn from these studies is that the conclusion of a causal relationship
      is currently not supported by the data. This is certainly true when an attempt is
      made to apply a world-wide risk ratio to the U.S. population, as was done in the
      U.S. Surgeon Generals report (1986) (U.S. Surgeon General).

PMID- 7730917
TI  - Dissent: The risk of lung cancer in nonsmokers in the United States: a causal
      association with environmental tobacco smoke.

PMID- 7730918
TI  - Large-scale health outcomes evaluation: how should quality of life be measured?
      Part I--Calibration of a brief questionnaire and a search for preference
      subgroups.

PMID- 7730919
TI  - Large-scale health outcomes evaluation: how should quality of life be measured?
      Part II--Questionnaire validation in a cohort of patients with advanced cancer.

PMID- 7730920
TI  - The importance of severity of illness adjustment in predicting adverse outcomes
      in the Medicare population.
AB  - The importance of using risk-adjusted mortality rates to measure quality of care
      is well-established. However, mortality rates may be an insensitive measure of
      quality for surgical patients since death is a relatively rare outcome. This
      study used Medicare files to identify, through chart abstraction, clinical
      postoperative complications of four surgical procedures (n = 8126) that could
      serve as measures of quality. Disease-specific severity of illness models using a
      moderate number of clinical variables and admission MedisGroups score models
      computed from approximately 250 clinical variables were compared in predicting
      postoperative adverse events. Initial differences between the two models
      disappeared upon cross-validation. Validated R-squareds and C statistics from
      models using half the data were generally positive, suggesting that these models
      had real, although modest, predictive power. We have shown that severity of
      illness on admission plays a role in predicting adverse events of surgery. Risk
      adjusted outcomes may potentially be useful in screening for quality shortfalls.

PMID- 7730921
TI  - Sequential and average attributable fractions as aids in the selection of
      preventive strategies.
AB  - Methods for estimating the attributable fraction based on a multivariate model
      for a dichotomous response have been extensively developed in the last decade.
      These methods provide the means for calculating the total attributable fraction
      for a set of exposure variables possibly adjusted for a set of confounding
      variables. In this paper, a procedure for stepwise calculation of attributable
      fractions is outlined. The purpose is to study the effect on risk of disease of
      preventing several exposures, one at a time, in different orderings. This
      procedure introduces the concepts of sequential and average attributable
      fractions as aids for attributing the risk of disease to different exposures. The
      procedure and concepts are illustrated by analyzing data from a cross-sectional
      study on the prevalence of some frequent symptoms of lung disease.

PMID- 7730922
TI  - Early ultrasound dating of pregnancy: selection and measurement biases.
AB  - Can using early ultrasound examinations to date pregnancy introduce information
      bias in perinatal research? Our purpose was to identify determinants of early
      ultrasound examinations and to compare early ultrasound to menstrual history
      dating. Between January 1987 and June 1989, 1159 white, largely middle class,
      prenatal patients were contacted for a prospective observational study. 876 (76%)
      agreed to participate. Of these 764 (87%) met the eligibility criteria for this
      analysis, namely singleton pregnancy, delivered after 20 weeks (spontaneous or
      induced, vaginal or c-section), with prenatal chart abstracted. Selection factors
      for early ultrasound identified in multivariate analysis were: bleeding in early
      pregnancy, OR = 1.9 (1.0, 3.5), attendance at health maintenance organization OR
      = 7.2 (3.4, 15), no insurance or Medicaid only OR = 0.3 (0.1, 0.6), and
      increasing time from last menstrual period to first prenatal visit in weeks OR =
      0.89 (0.85, 0.93). In conformity with previous results, ultrasound dating of
      pregnancy led to a higher estimate of preterm delivery (10 vs 7.6%), a higher
      estimate of term delivery (87.2 vs 82.7%) and a lower estimate of postterm
      delivery (2.8 vs 9.7%) than dating by menstrual history, p < 0.001. Selection
      factors and measurement issues, such as those described here, could introduce
      bias and should be carefully considered in the design, analysis and
      interpretation of perinatal research.

PMID- 7730923
TI  - Tree-structured prediction for censored survival data and the Cox model.
AB  - Prediction trees for the analysis of survival data are discussed. It is shown
      that trees are useful not only in summarizing the prognostic information
      contained in a set of covariates (prognostic classification), but also in
      detecting and displaying treatment-covariates interactions (subgroup analysis).
      The RECPAM approach to tree-growing is outlined; prognostic classification and
      subgroup analysis are then formulated within the RECPAM framework and on the
      basis of the Cox proportional hazards models with a priori strata. Two examples
      of data analysis are presented. The issue of cross-validation is discussed in
      relation to computationally cheaper model selection criteria.

PMID- 7730924
TI  - The efficacy of non-steroidal anti-inflammatory drugs (NSAIDS) for shoulder
      complaints. A systematic review.
AB  - The medical literature was evaluated with respect to the efficacy of NSAIDs for
      shoulder complaints. Nineteen randomized clinical trials met the selection
      criteria and were included in this review. Each publication was independently
      scored by two blinded reviewers, according to a standardized set of 17
      methodological criteria. The studies were ranked according to their total methods
      score (maximum 100 points). The methodological quality of the majority of the
      studies was rather disappointing; only 5 trials received a methods score
      exceeding 50 points. Furthermore, methodological criteria were often inadequately
      described, particularly those regarding the randomization procedure, co
      interventions and control of compliance. The three trials with the highest
      methods scores demonstrated superior short-term efficacy of NSAIDs in comparison
      with placebo intervention. Fourteen trials comparing two types of NSAIDs showed
      no conclusive evidence in favour of a particular NSAID with respect to efficacy
      or tolerability. Future studies should compare the benefit-risk ratios of NSAIDs
      and analgesics for shoulder complaints in order to establish whether the use of
      NSAIDs is more favourable than analgesics, despite the higher risk of adverse
      reactions from NSAIDs.

PMID- 7730925
TI  - Effects of "group detailing" on the prescribing of lipid-lowering drugs: a
      randomized controlled trial in Swedish primary care.
AB  - The objective was to study the effect of "academic group detailing" on the
      prescribing of lipid-lowering drugs in Swedish primary care. A randomized
      controlled trial was conducted, randomization being by group. Groups of doctors
      at 134 community health centres were randomly allocated to an intervention and a
      control group. The 67 intervention health centres were offered four sessions,
      conducted by a pharmacist, with group information on guidelines for the
      management of hyperlipidaemia. The number of prescriptions of lipid-lowering
      drugs per month increased in the intervention health centres and the increase was
      statistically different from the corresponding change in the control health
      centres among women in the age group 30-65 years (p = 0.03). The prescription of
      first-line lipid-lowering drugs increased by 20% in the intervention health
      centres (p = 0.03). "Academic group detailing" by pharmacists to primary care
      doctors can be an effective method for influencing prescribing practices.

PMID- 7730926
TI  - Quotation bias in reviews of the diet-heart idea.
AB  - Criticism of the diet-heart idea is often met with the argument that consensus
      committees have settled the issue unanimously. To see how these committees have
      explained discordant results, quotations from papers with such findings were
      sought in three recent authoritative reviews. Only two of twelve groups of
      controversial papers were quoted correctly, and only in one of the reviews. About
      half of the papers were ignored. The rest were quoted irrelevantly; or
      insignificant findings in favour of the hypothesis were inflated; or unsupportive
      results were quoted as if they were supportive. Only one of six randomized
      cholesterol-lowering trials with a negative outcome were cited and only in one of
      the reviews. In contrast, each review cited two, four, and six non-randomized
      trials with a positive outcome, respectively. It appears as if fundamental parts
      of the diet-heart idea are based on biased quotation.

PMID- 7730927
TI  - Staff role of nurse executives: suicide or survival strategy?

PMID- 7730928
TI  - Restructuring. Implications for nursing administration education.
AB  - The Council on Graduate Education for Administration in Nursing (CGEAN) was
      established to further develop and improve graduate education for administration
      in nursing. The Council seeks to identify the nature and direction of education
      for administration in nursing in various healthcare systems, providing guidelines
      for programs offering administration. A major goal of CGEAN is facilitating
      dialogue between nursing service administrators and graduate level educators who
      are engaged in teaching and research related to administration in nursing. This
      column, sponsored by the members of the Council, analyzes and responds to
      position statements and trends related to the delivery of health services and
      graduate education for administrators in nursing.

PMID- 7730929
TI  - Shared governance: nursing's 20th-century Tower of Babel.

PMID- 7730930
TI  - Whole systems shared governance: a model for the integrated health system.
AB  - The healthcare system is under renovation and renewal. In the process, roles and
      structures are shifting to support a subscriber-based continuum of care.
      Alliances and partnerships are emerging as the models of integration for the
      future. But how do we structure to support these emerging integrated
      partnerships? As the nurse executive expands the role and assumes increasing
      responsibility for creating new frameworks for care, a structure that sustains
      the point-of-care innovations and interdisciplinary relationships must be built.
      Whole systems models of organization, such as shared governance, are expanding as
      demand grows for a sustainable structure for horizontal and partnered systems of
      healthcare delivery. The executive will have to apply these newer frameworks to
      the delivery of care to provide adequate support for the clinically integrated
      environment.

PMID- 7730931
TI  - The role of the clinical nurse specialist and the nurse manager in case
      management.
AB  - Nursing case management was introduced into the acute care hospital as an
      approach to counteract the numerous changes occurring in the healthcare
      environment negatively affecting patient care. The authors address the
      development of case management at Bergan Mercy Medical Center, Omaha, Nebraska,
      and the integration of the nurse manager and clinical nurse specialist into this
      model.

PMID- 7730932
TI  - Changes related to care delivery patterns.
AB  - Nurse administrators, faced with a need to increase productivity and reduce costs
      in response to lower inpatient volumes and increased competition, are
      restructuring systems of care delivery. A survey of acute care hospitals was
      conducted to determine the extent of changes in nursing care delivery models,
      skill mix, assignment of non-nursing personnel to the nursing department, use of
      unlicensed assistive personnel, and registered nurse role changes in healthcare
      delivery systems employing unlicensed personnel.

PMID- 7730933
TI  - Charting the course for merger: key concepts for nurse executives.

PMID- 7730934
TI  - Troubling trends in healthcare delivery.

PMID- 7730935
TI  - Improving patient outcomes through system change: a focus on the changing roles
      of healthcare organization executives.
AB  - In this article, the authors report on a project that studied the impact of work
      redesign on the roles of hospital executives. Thirty-six in-depth interviews were
      conducted with executives from 13 VHA healthcare organizations that were
      considered excellent practice models in the area of work redesign. This report
      represents a broad, multidisciplinary perspective reflecting the ideas of various
      members of the healthcare management team. VHA hired Marie Manthey and Creative
      Nursing Management, Inc., to conduct the interviews in an objective manner and to
      assist with results interpretation.

PMID- 7730936
TI  - Administrative issues for use of nurse practitioners.
AB  - As nurse administrators increasingly use nurse practitioners in healthcare
      delivery systems to provide high-quality, more cost-effective care, they must
      recognize and take action on key practice issues--autonomy, title protection,
      admitting privileges, physician back-up, and reimbursement. Careful attention and
      action directed to enhancing nurse practitioner usefulness will increase the
      flexibility of nurse practitioner utilization within specific institutions and
      across a diverse network of healthcare delivery sites structured to provide
      continuity of care.

PMID- 7730937
TI  - Making sense of complex interventions.

PMID- 7730938
TI  - Alcohol: an ounce of prevention?

PMID- 7730939
TI  - Work rounds data collection.

PMID- 7730941
TI  - Primary and secondary prevention of alcohol problems: U.S. internist attitudes
      and practices.
AB  - OBJECTIVE: To describe internists' involvement in primary and secondary
      prevention of alcohol-related problems, and to evaluate relationships between
      preventive practices and training, attitudes, and work patterns. DESIGN: Cross
      sectional survey. PARTICIPANTS: A random sample of 152 board-certified
      internists, < or = 65 years old, who practiced primary care in the continental
      United States, was selected from the American Medical Association's master list.
      Ten were ineligible; 99 (70%) of the remaining 142 internists completed
      questionnaires. MAIN OUTCOME MEASURES: The authors evaluated the internists'
      preventive practices, including the frequency with which they assessed patients'
      alcohol consumption and advised patients about safe levels of alcohol
      consumption. The authors also evaluated the internists' opinions about safe
      levels of alcohol consumption, training and attitudes regarding advising patients
      about safe levels of consumption, and work patterns. RESULTS: Ninety-four percent
      of the respondents believed they had a responsibility to advise all patients
      about safe levels of alcohol consumption (primary prevention), though only 30%
      often/always did so. Eighty percent often/always advised patients who drank three
      or more drinks daily about safe levels of alcohol consumption (secondary
      prevention), but many (45%) did not routinely ask patients how much they drank
      daily. Preventive practices correlated positively with the number of hours/week
      internists practiced primary care, and with their belief in the effectiveness of
      preventive advice about alcohol consumption. CONCLUSIONS: Internists believe they
      have a responsibility for primary prevention of alcohol-related problems, but
      only a minority actively practice it. In contrast, many internists practice
      secondary prevention, offering advice about safe alcohol consumption to patients
      who drink three or more drinks daily. The effectiveness of such secondary
      prevention is limited, however, by incomplete screening regarding level of
      alcohol consumption.

PMID- 7730940
TI  - A nurse-coordinated intervention for primary care patients with non-insulin
      dependent diabetes mellitus: impact on glycemic control and health-related
      quality of life.
AB  - OBJECTIVE: To examine the impact of a nurse-coordinated intervention delivered to
      patients with non-insulin-dependent diabetes mellitus between office visits to
      primary care physicians. DESIGN: Randomized, controlled trial. SETTING: Veterans
      Affairs general medical clinic. PATIENTS: 275 veterans who had NIDDM and were
      receiving primary care from general internists. INTERVENTION: Nurse-initiated
      contacts were made by telephone at least monthly to provide patient education
      (with special emphasis on regimens and significant signs and symptoms of
      hyperglycemia and hypoglycemia), reinforce compliance with regimens, monitor
      patients' health status, facilitate resolution of identified problems, and
      facilitate access to primary care. MEASUREMENTS: Glycemic control was assessed
      using glycosylated hemoglobin (GHb) and fasting blood sugar (FBS) levels. Health
      related quality of life (HRQOL) was measured with the Medical Outcomes Study SF
      36, and diabetes-related symptoms were assessed using patients' self-reports of
      signs and symptoms of hyper- and hypoglycemia during the previous month. MAIN
      RESULTS: At one year, between-group differences favored intervention patients for
      FBS (174.1 mg/dL vs 193.1 mg/dL, p = 0.011) and GHb (10.5% vs 11.1%, p = 0.046).
      Statistically significant differences were not observed for either SF-36 scores
      (p = 0.66) or diabetes-related symptoms (p = 0.23). CONCLUSIONS: The
      intervention, designed to be a pragmatic, low-intensity adjunct to care delivered
      by physicians, modestly improved glycemic control but not HRQOL or diabetes
      related symptoms.

PMID- 7730942
TI  - Adjuvant chemotherapy does not affect employment in patients with early-stage
      breast cancer.
AB  - OBJECTIVE: To assess the impact of adjuvant chemotherapy for the management of
      breast cancer on subsequent patient employment. DESIGN: Retrospective cohort
      study. SETTING: University-affiliated community hospital cancer center. PATIENTS:
      Patients who were 18 to 65 years old and were diagnosed as having breast cancer
      stages 0, I, II, and IIIa between January 1986 and January 1991 were contacted
      and asked whether they had been employed at the time of the diagnosis. The 145
      patients who had breast cancer and who had been working at the time of diagnosis
      completed a questionnaire, which included questions regarding demographic
      characteristics, employment history, and the reasons for any period of
      unemployment. The 76 patients who had received adjuvant chemotherapy were
      compared with the 69 who had not. MEASUREMENTS AND RESULTS: The main endpoint was
      return to work by one, three, six, and 12 months after surgery. Of the 76
      patients who had received chemotherapy, 70 (92%) had resumed work by 12 months
      after treatment began. Of the 69 who had not been treated with chemotherapy, 65
      (94%) had resumed work in 12 months. The proportions of patients who had returned
      to work by one, three, and six months were similar in the two groups. Regression
      analyses demonstrated no significant confounding or interaction of adjuvant
      treatment with age, menopausal status, marital status, years of education, or
      type of job in regard to return to work. CONCLUSIONS: Adjuvant chemotherapy does
      not delay or prevent return to work in women treated for early-stage breast
      cancer.

PMID- 7730943
TI  - Physicians and nurses can be effective educators in coronary risk reduction.
AB  - OBJECTIVES: 1) To compare the impact of a brief physician or nurse education
      session with the impact of education provided by dietitians on patient knowledge
      regarding coronary risk factors, dietary recommendations, and compliance, and 2)
      to determine the value of additional formal dietary counseling on knowledge,
      dietary fat, and serum lipids. DESIGN: Primary care physicians and their office
      nurses were compared with inpatient dietitians by evaluating patient performance
      on a standardized test and three-day dietary food choices. Neither the educators
      nor the patients were aware of the study. Supplemental information was provided
      by a study dietitian and patients were reevaluated six weeks later. SETTING:
      Preventive cardiology program in a university-affiliated teaching hospital.
      PARTICIPANTS: Fifty consecutive patients referred to a preventive cardiology
      program who had received dietary and cardiac risk factor information within the
      preceding six weeks by a physician and office nurse (27) or an inpatient
      dietitian (23) were enrolled. Forty-five patients completed the study objectives.
      INTERVENTIONS: The patients completed a three-day food record, fasting lipids,
      and a test of knowledge of coronary risk factors and dietary concepts. The
      correct answers were discussed and a standard American Heart Association phase I
      diet was recommended. Six weeks later dietary food records, fasting lipids, and
      the test were repeated. MEASUREMENTS AND MAIN RESULTS: By participant recall, the
      dietitians (group II) spent an average of 30.6 +/- 25 minutes, compared with 8.2
      +/- 14.4 minutes by the physicians and nurses (group I) (p < 0.05). Group II
      patients had a higher total knowledge score, but they were no better in risk
      factors, weight control, or calculated dietary fat or cholesterol. There was no
      correlation between time spent and percentage of calories from fat or total test
      score. Six weeks after the program instruction the mean cholesterol level for all
      the participants was reduced, and group II had a lower fat intake than did group
      I, which was associated with significantly lower serum cholesterol, not present
      at entry. CONCLUSION: Primary care physicians and their office nurses, using less
      time than do dietitians, can be effective educators in providing patient
      education for coronary risk reduction and dietary fat intake. A second formal
      dietary consultation appears beneficial in improving compliance and lipid
      control.

PMID- 7730944
TI  - Rapid classification of positive blood cultures: validation and modification of a
      prediction model.
AB  - OBJECTIVE: 1) To validate a previously developed prediction model to aid
      physicians in differentiating true positive blood cultures from contaminants when
      the laboratory first calls with a positive result, and 2) to determine whether it
      could be modified to make it more practical for clinical use without altering
      predictability. DESIGN: A prospective cohort study of hospitalized patients
      (validation set) who had blood cultures done over a two-month period. Data
      collected included the seven independent predictors in the rapid classification
      of positive blood cultures model. The model was modified by eliminating one of
      the predictors (which required clinical data) but maintaining the laboratory
      components (morphologic and Gram stain characteristics, number of bottles
      positive, and time to positivity). The "blood culture episode" was the unit of
      evaluation. A blood culture episode was defined as a 48-hour period beginning
      with the drawing of blood for the culture and included any blood cultures
      obtained during that time period. Receiver operating characteristic (ROC) curve
      analysis was used to compare the predictabilities of these models. SETTING: A 550
      bed, university-affiliated county hospital that is a regional trauma center and
      has the only burn treatment unit in the region. PATIENTS: All adult (> or = 16
      years old) patients who had blood cultures done during the study period were
      eligible. Only patients with positive blood cultures were included in the study.
      INTERVENTIONS: None. MAIN RESULTS: Of 559 blood culture episodes identified, 139
      (25%) included the growth of one or more organisms; 62 (45%) of the 139 episodes
      represented true bacteremia. By ROC curve analysis, there was no significant
      difference in the mean areas under the curve (AUCs) (+/- SE) of the model in the
      derivation set (the previously developed model) (0.93 +/- 0.02) compared with the
      validation set (0.89 +/- 0.03; p = 0.29). In the validation set there was no
      significant difference in the mean AUCs when the model was modified (0.89 +/-
      0.03) by removing the clinical component vs the unmodified model (0.89 +/- 0.03;
      p = 0.98). CONCLUSIONS: The rapid classification of blood cultures model was
      validated in a general hospital population. Predictability of the model was not
      altered significantly by eliminating one component that required clinical data.
      Because the modified model requires only laboratory information, this may allow
      reporting of the probability of true bacteremia at the time a positive blood
      culture is initially reported to physicians. This information may aid physicians
      in interpreting the positive blood culture.

PMID- 7730945
TI  - Nutrition assessment and counseling practices: attitudes and interests of primary
      care physicians.
AB  - This survey examined the nutrition-related practices and office services of
      primary care physicians, and their preferred nutrition topics and educational
      methods. Respondents were 960 physicians from across the United States who were
      members of the Society of General Internal Medicine. A four-page mailed
      questionnaire with 21 items queried background information, nutrition-related
      clinical practices and office support systems, perceived self-efficacy for
      nutrition assessment and counseling, and nutrition-related educational
      preferences. Two-thirds of the respondents said they personally provided
      nutrition counseling. They reported moderate self-efficacy for nutrition
      counseling and lower confidence for using specific relapse prevention strategies.
      Greatest interest in further education related to chronic disease prevention and
      nutrition for the elderly, provided in convenient formats for practicing
      physicians.

PMID- 7730946
TI  - Receipt of recommended medical care in HIV-infected and at-risk persons.
AB  - The authors evaluated receipt of recommended medical care for 133 HIV-infected
      and 101 at-risk San Francisco public health clinic patients. Fewer than half the
      patients received syphilis and tuberculosis screening, hepatitis B immunity
      testing or vaccination, and tetanus boosters. The HIV-infected persons were
      significantly (p < or = 0.01) more likely than the at-risk persons to receive
      preventive care, except for interventions specific to women. More than 80% of the
      HIV-infected persons received CD4 testing, zidovudine and Pneumocystis carinii
      pneumonia prophylaxis, and pneumococcal vaccine. Only 40% of the at-risk persons
      reported having HIV-antibody testing recommended. Interventions to increase care
      delivery to HIV-infected and at-risk persons are needed.

PMID- 7730947
TI  - Beyond night float? The impact of call structure on internal medicine residents.
AB  - Limitation of resident working hours has been a critical issue for training
      programs in recent years. At Providence Medical Center, residents and faculty
      collaborated in developing goals, implementation strategies, and an evaluation
      process for a new ward float system. The goals of the float system were to reduce
      fatigue, facilitate education, maintain continuity of care, and minimize the
      negative impact of training on residents' personal lives. Evaluation revealed: 1)
      74% of the residents preferred Providence Medical Center float system (PMCF) to
      either night float (NF) (13%) or standard every-fourth-night call (EFNC) (13%);
      and 2) PMCF was perceived to ensure quality patient care to a greater degree than
      was NF, to better facilitate resident education than was NF, and to have a less
      negative impact on personal lives than was EFNC.

PMID- 7730949
TI  - Suprathreshold contrast perception across differences in mean luminance: effects
      of stimulus size, dichoptic presentation, and length of adaptation.
AB  - Contrast constancy across changes in mean luminance was reported to hold over a
      wide range of luminances in a few studies and to be limited to approximately 1
      log unit in another. The studies reporting contrast constancy over a wide
      luminance range used extended grafting stimuli presented dichoptically (bright
      stimulus to one eye and dim stimulus to the other) with long adaptation periods.
      The study reporting only limited constancy used narrow (1-octave-wide) Gabor
      patches presented side by side to both eyes with only a short (up to 5 s) period
      of adaptation. The current study was designed to determine whether differences in
      stimulus bandwidth, presentation format, or adaptation time could account for the
      different results reported. It was found that increasing stimulus size had no
      effect on the results. Dichoptic presentation with either a filter in front of
      one eye or calibrated screen luminance could account for the differences between
      the studies. When dichoptic presentation was combined with short adaptation
      periods (of a few seconds) an intermediate deviation from constancy was
      demonstrated. This effect suggests that the deviations from constancy
      demonstrated under free viewing are due to a lack of fast local adaptation and
      not to long-distance interactions across the retina.

PMID- 7730948
TI  - Clinical aspects of HIV infection in women.

PMID- 7730950
TI  - Time course of chromatic adaptation for color-appearance judgments.
AB  - Observer production of achromatic appearance has previously been used to measure
      the time course of chromatic adaptation for changes from daylight to incandescent
      illuminants at constant luminance, indicating an exponential decay of chromatic
      adaptation with a time constant of the order of 10 s. The work extends previous
      results in several ways. The psychophysical technique was significantly improved
      to provide more reliable estimates of color appearance as a function of
      adaptation duration, and the time course of chromatic adaptation was measured for
      six chromaticity changes. Three observers tracked achromatic appearance on a
      computer-controlled CRT display during transitions of 2-min duration between the
      various chromaticities. The results indicate that observer differences are
      statistically significant. However, differences in time course for different
      chromaticity changes are not statistically significant (within observer). Single
      or piecewise exponential decay functions cannot be fitted to the data. However,
      sum-of-two-exponentials functions provided accurate descriptions of the data. The
      results suggest two stages of adaptation: one extremely rapid (a few seconds) and
      the other somewhat slower (approximately 1 min). Chromatic adaptation at constant
      luminance was 90% complete after approximately 60 s.

PMID- 7730951
TI  - Objective assessment of image quality. II. Fisher information, Fourier crosstalk,
      and figures of merit for task performance.
AB  - Figures of merit for image quality are derived on the basis of the performance of
      mathematical observers on specific detection and estimation tasks. The tasks
      include detection of a known signal superimposed on a known background, detection
      of a known signal on a random background, estimation of Fourier coefficients of
      the object, and estimation of the integral of the object over a specified region
      of interest. The chosen observer for the detection tasks is the ideal linear
      discriminant, which we call the Hotelling observer. The figures of merit are
      based on the Fisher information matrix relevant to estimation of the Fourier
      coefficients and the closely related Fourier crosstalk matrix introduced earlier
      by Barrett and Gifford [Phys. Med. Biol. 39, 451 (1994)]. A finite submatrix of
      the infinite Fisher information matrix is used to set Cramer-Rao lower bounds on
      the variances of the estimates of the first N Fourier coefficients. The figures
      of merit for detection tasks are shown to be closely related to the concepts of
      noise-equivalent quanta (NEQ) and generalized NEQ, originally derived for linear,
      shift-invariant imaging systems and stationary noise. Application of these
      results to the design of imaging systems is discussed.

PMID- 7730952
TI  - Improved stability of w/o/w multiple emulsions by addition of hydrophilic colloid
      components in the aqueous phases.
AB  - To improve the stability of w/o/w multiple emulsions of arachis and olive oil the
      stabilizing effect of cherry gum, in combination with acacia and gelatin, was
      examined. The outstanding film-forming properties of this gum having already been
      noted; the effect of its addition to the aqueous phases was measured by the
      coalescence of emulsion globules. The enhanced stability, as compared to
      controls, was achieved at a minimum concentration which liquid crystal-bearing
      interfacial films seem to appear. Creation of more coherent interfaces,
      inhibiting transfer of phases, could be the basis of the improved stability of
      the emulsion.

PMID- 7730953
TI  - Poloxamer-coated three-ply-walled microcapsules for controlled delivery of
      diclofenac sodium.
AB  - The three-ply-walled-based system for controlled delivery of diclofenac was
      developed. The preparation of three-ply-walled microcapsules is essentially based
      on the technique of multiple-emulsion formation polymer at the interface followed
      by rigidization of the wall on evaporation of solvent. The protective colloids
      with surface-active properties were selected for the present study, viz. acacia
      gelatin, polyvinyl alcohol and sodium alginate. Ethyl cellulose was taken as
      hydrophobic polymer. The acacia/ethylcellulose/acacia-based three-ply-walled
      microcapsule system was selected for further studies. The three-ply-walled
      microcapsule were subsequently coated with poloxamer 188. The non-ionic
      hydrophilic surfactant coating retards uptake into the reticuloendothelial
      system. The coated and uncoated microcapsules were characterized for in vitro and
      in vivo performance. The microcapsules were noted to provide sustained release of
      the contained diclofenac. The plasma level observed indicated that poloxamer
      coating results in prolonged release of the drug. Organ distribution demonstrated
      a different distribution pattern when compared with uncoated microcapsules.

PMID- 7730954
TI  - An experimental investigation of enzyme release from poly(vinyl alcohol)
      crosslinked microspheres.
AB  - Crosslinked poly(vinyl alcohol) particles were prepared by the addition of
      glutaraldehyde into a PVA methanol/water solution in the presence of 0.2 N
      sulphuric acid. The polymer solution was dispersed in mineral oil in a jacketed
      vessel, with the aid of a six-blade impeller. Spherical crosslinked particles in
      the size range 30-80 microns were obtained by varying the degree of agitation
      or/and the amount of suspending agent. The crosslinked particles, after washing
      and drying, were placed into a protease enzyme solution for loading. The enzyme
      containing water-swollen particles were subsequently removed from the solution
      and the enzyme release kinetics determined by a UV spectrophotometer. The
      influence of the degree of crosslinking, ionic strength, pH, particle size, and
      degree of hydrophilicity of the polymer on the enzyme activity was retained
      during the adsorption-desorption studies. The release behaviour of enzymes from
      crosslinked PVA particles exhibited a biphasic kinetic model, with an initial
      fast release followed by a much slower release rate.

PMID- 7730955
TI  - Polymer-coated liposomes: improved liposome stability and release of cytosine
      arabinoside (Ara-C).
AB  - Liposomes of dimyristoylphosphatidylcholine (DMPC) or
      dipalmitoylphosphatidylcholine (DPPC), cholesterol (CHOL) and dicetylphosphate
      (DCP) containing Ara-C were prepared at pH 4.5 and subsequently coated with a
      derivatized polysaccharide, O-palmitoylpullulan (OPP). Encapsulation efficiencies
      (EEF) of DMPC:CHOL:DCP (3:1:2 mol ratio) and DPPC:CHOL:DCP (3:1:0.5 mol ratio)
      liposomes were respectively 28 and 40% before and 15 and 27% after coating with
      polymer. Stabilities of liposomes in sodium cholate (SC) concentrations up to 16
      mM at pH 5.6 or in SC solutions at pH 7.4 were increased by coating with OPP. At
      pH 2.0 and 37 degrees C, Ara-C was released at a slow rate, kuo (uncoated) or kco
      (coated), for 24 h after an initial rapid release phase that lasted for about 6 h
      and the ratio kuo/kco, was 1.9 and 5.7 for the DMPC:CHOL:DCP and the
      DPPC:CHOL:DCP compositions respectively. At pH 7.4 and 37 degrees C in the
      presence of 10 mM SC, the ratio kuo/kco was 5.1 and 1.4 respectively. It is
      concluded that coating liposomes with OPP increases the potential of using
      liposomes as a drug delivery system in harsh environments such as encountered
      after oral administration, although the magnitude of the effect is dependent on
      the liposome composition.

PMID- 7730956
TI  - Collagen microparticles: preparation and properties.
AB  - Collagen microparticles (CMPs) of diameters ranging from about 3 to 40 microns
      were prepared by the method of emulsifying and cross-linking native collagen. The
      particle size was mainly controlled by the molecular weight of the collagen used:
      an increase in denaturation of the collagen resulted in smaller particle sizes.
      Consequently, controlled denaturation is the best method to control the size of
      CMPs. Total denaturation results in the degradation product gelatin and
      subsequently yields very small nanoparticles with a minimum diameter of about 0.1
      micron. Collagen microparticles can be used as carriers for lipophilic drugs e.g.
      retinol, tretinoin, or tetracaine and lidocaine in free base form. Another
      feature of the biodegradable CMPs is their thermal stability, thus their
      sterilization can be readily achieved.

PMID- 7730957
TI  - Biodegradable microcapsules prepared by a w/o/w technique: effects of shear force
      to make a primary w/o emulsion on their morphology and protein release.
AB  - A water-in-oil-in-water (w/o/w) technique, sometimes known as in-water drying
      method, was used to prepare microcapsules consisting of polylactic acid and
      poly(lactide-co-glycolide). The influence of shear force to produce an initial
      water-in-oil (w/o) emulsion on the characteristics of microcapsules and protein
      release was investigated. Bovine serum albumin (BSA) was used as the model
      protein drug for encapsulation. The initial w/o emulsion was prepared by a
      Polytron homogenizer. The shear rate was varied from 11 to 23 krpm to produce w/o
      emulsions with different shear forces. This study revealed pronounced effects of
      shear force on the characteristics of microcapsules and release profiles of BSA.
      Depending on the degree of the shear applied, the inner structure of
      microcapsules showed very different morphology, which was responsible for
      different release patterns. A low shear produced microcapsules with a high
      initial burst release of BSA, whereas microcapsules using a high shear exhibited
      a controlled release of protein without any initial burst release. Also, at a
      given shear force, a variation in polymer composition of microcapsules was found
      to be effective in controlling the release characteristics of protein. Thus, the
      homogenization technique should be carefully considered in designing
      microcapsules with desirable release profiles of proteins and an adequate period
      of protein delivery.

PMID- 7730958
TI  - A new method for the synthesis of smooth, round, hydrophilic protein microspheres
      using low concentrations of polymeric dispersing agents.
AB  - A new method for the synthesis of protein microspheres of wide size range having
      good spherical geometry and hydrophilicity using very low concentrations of
      polymeric dispersing agents is reported. The method involves the use of around 1%
      solution of a biomedical grade aliphatic polyurethane in a mixture of a hexane
      and dichloromethane as the dispersion medium, as opposed to a 25-30% solution of
      polymeric dispersing agents employed by previous workers to effect steric
      stabilization of the protein solution droplets. The versatility of the method is
      demonstrated by the synthesis of albumin microspheres, as well as those of the
      amphiphilic protein casein, the latter being more difficult to prepare by
      surfactant stabilization techniques. Significant advantages of the method include
      the avoidance of surfactants which become adsorbed on the particles and influence
      tissue reactions and drug release, and the ease of removal of the polymeric
      stabilizer from the final product. The method may find application for the
      preparation of a wide range of protein and polysaccharide microspheres for
      medical use.

PMID- 7730959
TI  - Effect of varying drug loading on particle size distribution and drug release
      kinetics of verapamil hydrochloride microspheres prepared with cellulose esters.
AB  - Microspheres containing two different drug loadings of a calcium channel blocker,
      verapamil hydrochloride, were prepared with three different cellulose esters
      namely cellulose acetate (CA), cellulose acetate propionate (CAP) and cellulose
      acetate butyrate (CAB) of approximately similar molecular weights using the
      emulsion-solvent evaporation method. Increasing the drug loading from 33.3 to 50%
      w/w increased the geometric mean diameter of the microspheres as well as the T50%
      values, i.e. time required to release 50% of the drug from microspheres prepared
      with all the three cellulose esters. Drug release from the microspheres was
      affected by the nature of polymer. Mathematical modelling of drug release data by
      fitting the data to various equations revealed that the data did not fit the
      conventional Higuchi's and Baker-Lonsdale's models for drug release from
      spherical matrices. Instead, the data fitted the log-probability and the Weibull
      models quite well.

PMID- 7730960
TI  - Quality improvement of spray-dried, protein-loaded D,L-PLA microspheres by
      appropriate polymer solvent selection.
AB  - The aim was to study the effect of the type of polymer solvent on characteristics
      of microspheres produced by spray drying. The water-soluble model protein, bovine
      serum albumin (BSA) was microencapsulated into biodegradable poly(D,L-lactic
      acid) using the following 10 different polymer solvents: acetaldehyde dimethyl
      acetal, acetone, dichloromethane, dioxane, ethyl acetate, ethyl vinyl ether,
      nitromethane, tetrahydrofuran, 1,1,1-trichloroethane, and 1,1,2
      trichloroethylene. These solvents having similar toxicity levels differ greatly
      in their physico-chemical characteristics such as boiling point, vapour pressure,
      miscibility and interfacial tension with an aqueous phase, and solubility
      parameter. The effect of these solvents on microsphere morphology was studied by
      SEM-micrographs. Regular particle morphology was obtained when dichloromethane,
      ethyl acetate, or nitromethane was used as the polymer solvent, whereas the
      trichlorinated solvents, tetrahydrofuran, and dioxane produced a substantial
      number of coalesced particles. The results are interpreted in terms of boiling
      point, vapour pressure, and polymer-solvent affinity. Further, BSA-loading and 
      integrity in the microspheres, and burst release were analysed. The theoretical
      loading of 2.9% was attained with dichloromethane, ethyl acetate and
      nitromethane, in agreement with observations of particle morphology. HPLC- and
      SDS-PAGE analysis of the microencapsulated BSA did not show any protein
      degradation or dimerization, whereas solid-phase ELISA clearly revealed that the
      in vitro protein antigenicity was substantially reduced (50%), particularly by
      water miscible solvents. Dichloromethane and ethyl acetate did not show any
      detrimental effect on protein antigenicity. Finally, burst release could be
      related again to particle morphology, with dichloromethane and nitromethane
      giving a burst release of only 5%. In conclusion, dichloromethane, ethyl acetate
      and nitromethane proved to be the most suitable solvents for the polymer-protein
      system studied.

PMID- 7730961
TI  - Detection and incidence of the tetracycline resistance determinant tet(M) in the
      microflora associated with adult periodontitis.
AB  - Subgingival plaque samples were collected from 68 patients with adult
      periodontitis, enumerated on Trypticase-soy blood agar plates, with and without
      tetracycline at 4 micrograms/ml, and incubated anaerobically for 5 days. Each
      different colony morphotype was enumerated, and a representative colony was
      subcultured for identification and examined for the tetracycline resistance gene
      tet(M). Both PCR amplification and DNA hybridization, using a fragment of tet(M)
      from Tn1545, were used to detect tet(M). The PCR primers (5'-GACACGCCAGGACATATGG
      3' and 5'-TGCTTTCCTCTTGTTCGAG-3') were chosen to amplify a 397 bp region of
      tet(M). Tetracycline-resistant bacteria represented approximately 12% of the
      total viable count. The percentage of tet(M)-positive bacteria in the
      tetracycline resistant microflora varied from < or = 0.05 to 83% (mean of 10%).
      tet(M) was detected in 60% of 204 tetracycline-resistant strains subcultured and
      identified. The tet(M) containing strains consisted of streptococci (55%, mainly
      S. intermedius, S. oralis, S. sanguis, and Streptococcus SM4), Actinomyces D01
      (14%), Bifidobacterium D05 (11%), and Veillonella spp. (10%). Tetracycline
      resistant strains in which tet(M) was not detected included the Prevotella and
      Bacteroides species (41%, mainly Bacteroides D28, P. intermedia, P. nigrescens,
      and P. oris). These results suggest that tet(M) is widely spread in the adult
      periodontal microflora, but it appears, with the exception of S. intermedius, to
      be mainly associated with microorganisms not considered to be
      periodontopathogens. Assessment of other tetracycline-resistant genes in oral
      organisms is needed to fully evaluate the nature of resistance to this antibiotic
      in the oral flora.

PMID- 7730962
TI  - Reduction of plaque formation and gingivitis by a dentifrice containing triclosan
      and copolymer.
AB  - A 6-month, single-blind and parallel clinical study was conducted to compare the
      effects of dentifrice containing 0.3% triclosan and 2.0% of copolymer
      (methoxyethylene and maleic acid) with a customary oral hygiene procedure on
      supragingival plaque formation and gingivitis. The 124 subjects were stratified
      into two balanced groups on the basis of their baseline plaque and gingivitis
      scores. After complete oral prophylaxis, subjects were assigned to use either a
      triclosan/copolymer dentifrice or to practice their customary oral hygiene care
      for 6 months. Plaque formation and gingivitis were scored at 3 and 6 months.
      After 3 and 6 months, triclosan/copolymer produced 7.17% and 12.07% significantly
      greater reduction of plaque formation than the customary oral hygiene group,
      respectively. Triclosan/copolymer significantly reduced gingivitis by 5.20% at 3
      months, while no significant differences between the two groups were observed at
      6 months. Likewise, triclosan/copolymer provided 8.70% and 16.33% significantly
      greater reduction of plaque severity index at 3- and 6-month evaluation,
      respectively. Gingivitis severity index was significantly reduced by 25% at 3
      months, but there were no differences between the two groups at 6 months. These
      results indicate that the triclosan/copolymer dentifrice was better than the
      customary oral hygiene care in preventing supragingival plaque formation up to 6
      months and in reducing gingivitis up to 3 months.

PMID- 7730963
TI  - Periodontal tissue regeneration on the surface of synthetic hydroxyapatite
      implanted into root surface.
AB  - Several studies have demonstrated that periodontal ligament (PDL)-derived cells
      can form a new connective tissue attachment (NCTA) not only on denuded dentin but
      also on nondental inorganic materials. Although the cellular response to these
      materials may be different than that to denuded dentin, the process of NCTA
      formation on the surface of non-dental inorganic materials is still undetermined.
      In the present study, we compared the process of NCTA formation on the surface of
      an inorganic material with that on a denuded root surface by implanting a block
      of synthetic hydroxyapatite (HA) into a root cavity prepared on the first molar
      of a rat. We then observed tissue regeneration under conditions where the PDL
      derived cells could populate the HA surface using an occlusive membrane. After
      fibrinous exudation at 3 days postoperatively, granulation tissue from the PDL
      filled the space between the HA block and the membrane at 1 week. Four weeks
      after the operation, although the granulation tissue increased in density at the
      interface to the HA block, no obvious deposition of cementum-like tissue was seen
      on the HA block. Six weeks after the operation, the deposition of cementum was
      observed on the surface of the HA block. The deposition of cementum became more
      extensive and insertion of collagen fibers into the cementum layer became more
      obvious 8 weeks postoperatively. Twelve weeks after the operation, the cementum
      covered almost the entire surface of the HA block. On the surface of the denuded
      dentin in control teeth, cementum deposition was seen at 4 weeks after the
      operation and increased in thickness from 6 weeks on.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7730964
TI  - Periodontal repair in dogs: recombinant human bone morphogenetic protein-2
      significantly enhances periodontal regeneration.
AB  - This study evaluated bone and cementum regeneration following periodontal
      reconstructive surgery using recombinant human bone morphogenetic protein-2
      (rhBMP-2) in six beagle dogs. Surgically created mandibular supraalveolar
      premolar tooth defects in contralateral jaw quadrants were randomly assigned to
      receive rhBMP-2 or control vehicle. Clinical defect height was prepared to 5 mm.
      rhBMP-2 was applied with synthetic bioerodable particles and autologous blood
      using 20 micrograms rhBMP-2 per 100 microliters implant volume. Flaps were
      advanced to submerge the teeth and sutured. The dogs were sacrificed 8 weeks
      postsurgery. Histometric recordings included defect height, height and area of
      alveolar bone regeneration, height of cementum regeneration, root resorption, and
      ankylosis. Group means, standard deviations, and P values are shown (Student t
      test; n = 6). Histometric defect height for rhBMP-2 and control defects was 3.7
      +/- 0.3 and 3.9 +/- 0.4 mm, respectively (P = 0.446). Height of alveolar bone
      regeneration amounted to 3.5 +/- 0.6 and 0.8 +/- 0.6 mm for rhBMP-2 and control
      defects, respectively (P = 0.000). Corresponding values for bone area were 8.4 +/
      4.5 and 0.4 +/- 0.5 mm2, respectively (P = 0.006). Cementum regeneration was
      observed in all experimental defects (17/17) and in 15 out of 17 controls,
      averaging 1.6 +/- 0.6 and 0.4 +/- 0.3 mm for rhBMP-2 and control defects,
      respectively (P = 0.005). Small amounts of root resorption were seen in rhBMP-2
      defects, whereas controls exhibited substantial resorption (0.2 +/- 0.1 and 1.1
      +/- 0.3 mm, respectively; P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730965
TI  - Bacterial-stimulated cytokine production of peripheral mononuclear cells from
      patients of various periodontitis categories.
AB  - Periodontitis is a general term for disease categories, including juvenile
      periodontitis (JP), rapidly progressive periodontitis (RPP), and adult
      periodontitis (AP), which may or may not share a common etiology and
      pathogenesis. These disease categories are characterized by differences in
      progression of tissue destruction and differences in age group susceptibility,
      but not, to our knowledge, by differences in cytokine responses of inflammatory
      cells. The present study examined blood cell counts and interindividual variation
      in the ability of PBMC of patients in three different categories of periodontitis
      to produce cytokines after stimulation with different oral bacterial species in
      vitro. The AP group had a significantly lower production of IL-1ra when
      stimulated with Porphyromonas gingivalis (P.g.) and Actinobacillus
      actinomycetemcomitans (A.a.) (P < 0.05). Streptococcus sanguis (S.s.), which is
      associated with normal periodontal conditions, induced extremely high levels of
      IL-1 alpha and TNF alpha production in all groups. The RPP group had a
      significantly higher number of monocytes (MC) than the AP group (P < 0.05).
      Additionally, JP patients had a significantly higher concentration of
      polymorphonuclear granulocytes compared to juvenile controls (P < 0.05). In
      conclusion, IL-1 alpha, TNF alpha, or IL-6 production by peripheral blood MC
      after in vitro stimulation with oral bacterial type stains may not distinguish
      different categories of periodontitis. The results support the hypothesis that
      the cytokine IL-1ra is produced in different concentrations in the two groups:
      RPP and AP. Furthermore, elevated MC concentration in the RPP group compared to
      the AP group may be an important pathogenic feature in RPP.

PMID- 7730966
TI  - Compliance with supportive periodontal treatment in private periodontal practice.
      A 14-year retrospective study.
AB  - The purpose of this study was to determine the degree of compliance with
      supportive periodontal treatment (SPT) recommended in private periodontal
      practice and to determine if any significant differences existed in the
      characteristics of compliant, non-compliant, and erratically compliant patients.
      The study covered a period of 14 years (1977 to 1991) and included 521 patients
      who were classified by sex, age, socioeconomic class, disease severity, treatment
      rendered, and the year maintenance began. Compliance was categorized into four
      groups: complete compliance, erratic compliance, patients who discontinued SPT,
      and patients who never presented for SPT. Females began SPT more often than males
      (P = 0.054). Only 27.4% of the patients were in complete compliance at the end of
      the study. A significantly greater percentage of females (P = 0.032) and patients
      who had been treated by only scaling and root planing (P = 0.014) were in
      complete compliance. Drop-out rates from SPT tended to decrease during the first
      6 years from 13.9% in the first 2 years to 9% in the sixth year. Thereafter, the
      percentage of patients presenting for SPT stabilized at 48.4% after 6 and 43.2%
      after 11 years. Younger patients (P = 0.04), those who had received only scaling
      and root planing (P = 0.008), and individuals in socioeconomic class I (P =
      0.017) had a significantly lower tendency to drop out. The results confirm that
      compliance to SPT in private periodontal practice is far from ideal. Suggestions
      for improving compliance are discussed.

PMID- 7730967
TI  - The successful use of osseointegrated implants for the treatment of the
      recalcitrant periodontal patient.
AB  - This study reports the successful use of osseointegrated implants to replace
      teeth in patients whose periodontal disease has been categorized as recalcitrant.
      It includes partially and totally endentulous jaws. A total of 309 implants
      placed by two periodontists practicing in traditional office settings were
      included in the survey. Of the 132 mandibular implants, 4 failed, for a success
      rate of 97%; and 3 of the 177 maxillary implants failed, for a success rate of
      98%. There were 21 implants placed in 1985; 38 in 1986 and 1987; 185 from 1988 to
      1990; 42 in 1991; and 23 in 1992. The report includes 42 mandibular and 50
      maxillary prostheses, none of which has failed. One female mandibular case was
      converted from 2 posterior free-standing to a full arch prosthesis when the
      anterior teeth failed periodontally. These results demonstrate that individuals
      with a strong susceptibility to periodontal disease can be treated successfully
      with osseointegrated implants.

PMID- 7730968
TI  - Detection of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and
      Bacteroides forsythus in an A. actinomycetemcomitans-positive patient population.
AB  - A population of 33 subjects were selected on the basis that all had tested
      positive for A, actinomycetemcomitans at some time during the prior 7 years. Most
      subjects (31/33) belonged to families with a proband with confirmed localized
      juvenile periodontitis (JP); however, most subjects had no evidence of the
      typical lesions associated with JP. Two additional subjects with rapidly
      progressive periodontitis, known to be positive for A. actinomycetemcomitans,
      were also recruited. The patients with a history of JP had been treated, but were
      no longer enrolled in a regular maintenance program. With 3 exceptions, the
      subjects had not received any dental treatment or antibiotics in the past 3
      months. One aim of the study was to determine the prevalence of A.
      actinomycetemcomitans, P. gingivalis, and B. forsythus in this population. The
      main purpose was to compare the relative sensitivity of various methods for
      detecting these periodontal pathogens. Pooled subgingival plaque samples were
      collected from all the mesial surfaces and aliquots of the suspension processed
      for the detection of A. actinomycetemcomitans by culture and indirect
      immunofluorescence (IF) to serotypes a, b, and c. P. gingivalis and B. forsythus
      were monitored with a DNA probe and IF. With culture, A. actinomycetemcomitans
      was detected in 39.4% of the samples, at a mean level of 0.64% of the cultivable
      counts. With IF, A. actinomycetemcomitans was detected in 81.8% of the samples,
      at levels of 0.40, 0.79, and 0.17% of the total counts for serotypes a, b and c
      respectively. Overall, IF was more likely to detect A. actinomycetemcomitans, P.
      gingivalis, and B. forsythus than any of the other methods.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7730969
TI  - Mycoplasmas in plaque and saliva of children and their relationship to
      gingivitis.
AB  - Gingivitis is common in children but its etiology is not well understood. Results
      of earlier studies have suggested that mycoplasmas may have a role in the
      disease. In this study two plaque samples and one stimulated saliva sample were
      taken from each of a group of sixty (60) 5 to 9 year-old children and cultured
      selectively for mycoplasmas. Subjects had been selected on the basis of gingival
      status buccal to the most posterior tooth in an upper quadrant, 20 each having
      scores 0, 1, or 2 at this site using the Loe and Silness index. Plaque samples
      were taken from the adjacent tooth surface and from a second posterior site where
      the adjacent gingiva was free of signs of inflammation. Mycoplasmas were cultured
      from 54 saliva samples and from 57 plaque samples. Isolation frequency and
      numbers of mycoplasmas in relation to total anaerobic counts were consistently
      related to gingivitis scores in both plaque and saliva samples, with higher
      frequencies and proportions with increasing levels of gingival inflammation at
      the selected site. In plaque samples this finding held good for both comparisons
      between groups of subjects and for those between test and control sites within
      subjects. Findings would appear to confirm the suggestions of earlier studies
      that mycoplasmas in the oral cavity are associated with gingivitis in children.

PMID- 7730971
TI  - Properties of voltage-gated chloride channels of the ClC gene family.
AB  - We review the properties of ClC chloride channels, members of an expanding gene
      family originally discovered by the cloning of the ClC-0 chloride channel from
      Torpedo electric organ. There are at least nine different ClC genes in mammals,
      several of which seem to be expressed ubiquitously, while others are expressed in
      a highly specific manner (e.g. the muscle-specific ClC-1 channel and the kidney
      specific ClC-K channels). The newly cloned rat ClC-4 is strongly expressed in
      liver and brain, but also in heart, muscle, kidney and spleen. ClC chloride
      channels are structurally unrelated to other channel proteins and have twelve
      putative transmembrane domains. They function as multimers with probably four
      subunits. Functional characterization is most advanced with ClC-0, ClC-1
      (mutations which cause myotonia) and ClC-2, a swelling-activated chloride
      channel. Many of the new ClC family members cannot yet be expressed functionally.

PMID- 7730970
TI  - Structure/function studies of mammalian Na-H exchangers--an update.
AB  - Four mammalian Na+/H+ exchangers have recently been cloned. Despite the
      structural similarity, these Na+/H+ exchanger isoforms differ in kinetic
      characteristics and their response to external stimuli. The present review deals
      with the recent developments in their functional characterization and their short
      term regulation.

PMID- 7730972
TI  - Vesicular targeting and the control of ion secretion in epithelial cells:
      implications for cystic fibrosis.
AB  - Non-polarized HT-29 colonic epithelial cells fail to respond to cyclic AMP
      generating agonists with increases in plasma membrane anion conduction. Radio
      isotopic efflux and patch-clamp experiments revealed that both undifferentiated
      and differentiated HT-29 colonocytes possess volume- and Ca(2+)-activated Cl-
      channels. However, only within the apical plasma membranes of the latter were
      cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels found.
      CFTR was expressed equally well in both non-polarized and polarized colonocytes.
      Lack of CFTR-dependent anion conduction was shown to be the result of CFTR
      retention within a peripheral intracellular compartment. We demonstrate that upon
      polarization, CFTR moves to the apical plasma membrane via a Brefeldin A (BFA)
      sensitive intracellular trafficking pathway.

PMID- 7730973
TI  - Volume-activated chloride currents associated with the multidrug resistance P
      glycoprotein.
AB  - The ability to regulate volume is an important property of most, if not all
      cells. In epithelial cells, amongst others, cell volume-activated chloride
      channels are central to this response. The molecular identities of these channels
      are not yet known. Expression of the human multidrug resistance P-glycoprotein (P
      gp) has been associated with cell volume-regulated chloride currents, although
      the nature of this association is the subject of debate. Recent data indicate
      that P-gp acts by regulating the activation of an endogenous channel protein. In
      this review, evidence associating P-gp with cell volume-activated chloride
      currents, and the possible mechanisms by which this might be achieved, are
      discussed.

PMID- 7730974
TI  - Mammalian ion-coupled solute transporters.
AB  - Active transport of solutes into and out of cells proceeds via specialized
      transporters that utilize diverse energy-coupling mechanisms. Ion-coupled
      transporters link uphill solute transport to downhill electrochemical ion
      gradients. In mammals, these transporters are coupled to the co-transport of H+,
      Na+, Cl- and/or to the countertransport of K+ or OH-. By contrast, ATP-dependent
      transporters are directly energized by the hydrolysis of ATP. The development of
      expression cloning approaches to select cDNA clones solely based on their
      capacity to induce transport function in Xenopus oocytes has led to the cloning
      of several ion-coupled transporter cDNAs and revealed new insights into
      structural designs, energy-coupling mechanisms and physiological relevance of the
      transporter proteins. Different types of mammalian ion-coupled transporters are
      illustrated by discussing transporters isolated in our own laboratory such as the
      Na+/glucose co-transporters SGLT1 and SGLT2, the H(+)-coupled oligopeptide
      transporters PepT1 and PepT2, and the Na(+)- and K(+)-dependent neuronal and
      epithelial high affinity glutamate transporter EAAC1. Most mammalian ion-coupled
      organic solute transporters studied so far can be grouped into the following
      transporter families: (1) the predominantly Na(+)-coupled transporter family
      which includes the Na+/glucose co-transporters SGLT1, SGLT2, SGLT3 (SAAT-pSGLT2)
      and the inositol transporter SMIT, (2) the Na(+)- and Cl(-)-coupled transporter
      family which includes the neurotransmitter transporters of gamma-amino-butyric
      acid (GABA), serotonin, dopamine, norepinephrine, glycine and proline as well as
      transporters of beta-amino acids, (3) the Na(+)- and K(+)-dependent
      glutamate/neurotransmitter family which includes the high affinity glutamate
      transporters EAAC1, GLT-1, GLAST, EAAT4 and the neutral amino acid transporters
      ASCT1 and SATT1 reminiscent of system ASC and (4) the H(+)-coupled oligopeptide
      transporter family which includes the intestinal H(+)-dependent oligopeptide
      transporter PepT1.

PMID- 7730975
TI  - Tetrodotoxin-resistant persistent Na+ current underlying pacemaker potentials of
      fish gonadotrophin-releasing hormone neurones.
AB  - 1. Gonadotrophin-releasing hormone (GnRH)-immunoreactive terminal nerve (TN)
      cells show endogenous regular beating discharges, which may be related to their
      putative neuromodulator functions. The ionic mechanism underlying the pacemaker
      potential was studied using intracellular and patch-pipette current clamp
      recordings from a whole brain in vitro preparation of a small fish brain. 2. The
      pacemaker potentials were resistant to 1.5-3 microM tetrodotoxin (TTX) and were
      not affected by Ca2+ channel blockers (amiloride, Ni2+, Co2+, Cd2+) or in Ca(2+)
      free solution. In contrast, the pacemaker potentials were readily blocked by
      substituting tetramethylammonium or choline for Na+ in the perfusing solution,
      and the resting membrane potential became more hyperpolarized than the control
      level. 3. The present results suggest that the TTX-resistant persistent Na+
      current, INa(slow), supplies the persistent depolarizing drive and plays an
      important role in the generation of pacemaker potentials in TN GnRH cells.

PMID- 7730976
TI  - ATP utilization for calcium uptake and force production in skinned muscle fibres
      of Xenopus laevis.
AB  - 1. A method has been developed to discriminate between the rate of ATP hydrolysis
      associated with calcium uptake into the sarcoplasmic reticulum (SR) and force
      development of the contractile apparatus in mechanically or saponin-skinned
      skeletal muscle fibres. The rate of ATP hydrolysis was determined in fibres of
      different types from the iliofibularis muscle of Xenopus laevis by enzymatic
      coupling of ATP re-synthesis to the oxidation of NADH. 2. The ATPase activity was
      determined before and after exposure of the preparations for 30 min to a solution
      containing 0.5% Triton X-100, which effectively abolishes the SR ATPase activity.
      The fibres were activated in a solution containing 5 mM caffeine to ensure that
      calcium uptake into the SR was maximal. 3. At saturating Ca2+ concentrations the
      actomyosin (AM) and SR ATPase activities in fast-twitch fibres, at 4.3 degrees C,
      amounted to 1.52 +/- 0.07 and 0.58 +/- 0.10 mumol s-1 (g dry wt)-1, respectively
      (means +/- S.E.M.; n = 25). The SR ATPase activity was 25% of the total ATPase
      activity. At submaximal calcium concentrations the AM ATPase activity varied in
      proportion to the isometric force. 4. The calcium sensitivity of the SR ATPase
      was larger than that of the AM ATPase and its dependence on [Ca2+] was less
      steep. The AM ATPase activity was half-maximal at a pCa of 6.11 (pCa = -log
      [Ca2+]) whereas the SR ATPase activity was half-maximal at a pCa of 6.62. 5. In
      Triton X-100-treated fibres, at different 2,3-butanedione monoxime (BDM)
      concentrations, the AM ATPase activity and isometric force varied proportionally.
      The SR ATPase activity determined by extrapolation of the total ATPase activity
      in mechanically skinned or saponin-treated fibres to zero force, was independent
      of the BDM concentration in the range studied (0-20 mM). The values obtained for
      the SR ATPase activity in this way were similar to those obtained with Triton X
      100 treatment. 6. The AM ATPase activity in slow-twitch fibres amounted to 0.74
      +/- 0.13 mumol s-1 (g dry wt)-1, i.e. about a factor of two smaller than in fast
      twitch fibres. The SR ATPase activity amounted to 0.47 +/- 0.07 mumol s-1 (g dry
      wt)-1, i.e. rather similar to the value in fast-twitch fibres. The proportion of
      the total ATPase activity that was due to SR ATPase (40%) was larger than in fast
      twitch fibres. 7. The temperature dependence of the AM and SR ATPase activities
      in fast-twitch fibres differed. In the temperature range 5-10 degrees C, the
      relative changes in AM and SR ATPase activities for a 10 degrees C temperature
      change (Q10) were 3.9 +/- 0.3 and 7.2 +/- 1.5, respectively.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7730977
TI  - Effects of creatine phosphate and P(i) on Ca2+ movements and tension development
      in rat skinned skeletal muscle fibres.
AB  - 1. Mechanically skinned fast-twitch (FT) and slow-twitch (ST) muscle fibres of
      the rat were used to investigate the effects of fatigue-like changes in creatine
      phosphate (CP) and inorganic phosphate (P(i)) concentration on Ca(2+)-activation
      properties of the myofilaments as well as Ca2+ movements into and out of the
      sarcoplasmic reticulum (SR). 2. Decreasing CP from 50 mM to zero in FT fibres
      increased maximum Ca(2+)-activated tension (Tmax) by 16 +/- 2% and shifted the
      mid-point of the tension-pCa relation (pCa50) to the left by 0.28 +/- 0.03 pCa
      units. In ST fibres, a decrease of CP from 25 mM to zero increased Tmax by 9 +/-
      1% and increased the pCa50 by 0.16 +/- 0.01 pCa units. The effect of CP on Tmax
      was suppressed in both fibre types by prior treatment with 0.3 mM FDNB (1-fluoro
      2,4-dinitrobenzene), suggesting that these effects may occur via changes in
      creatine kinase activity. 3. Increases of P(i) in the range 0-50 mM reduced the
      pCa50 and Tmax in both fibre types. These effects were more pronounced in ST
      fibres than in FT fibres in absolute terms. However, normalization of the results
      to resting P(i) levels appropriate to both fibre types (1 mM for FT and 5 mM for
      ST fibres) revealed similar decreases in Tmax (approximately 39% at 25 mM P(i)
      and approximately 48% at 50 mM P(i)) and pCa50 (0.25 pCa units at 25-50 mM P(i)).
      The depressant action of P(i) on both parameters was considerably reduced when
      the rise in P(i) was accompanied by an equivalent reduction in [CP]. 4. Tension
      development in the presence of complex, fatigue-like milieu changes (40 mM P(i)
      for FT; 20 mM P(i) for ST) was decreased by 35-40% at a constant myoplasmic
      [Ca2+] of 6 microM in both fibre types. 5. SR Ca2+ loading at a myoplasmic [Ca2+]
      of 100 nM was found to increase abruptly when the [P(i)] during loading was
      increased to near 9 mM. At a myoplasmic [Ca2+] of 300 nM, the threshold P(i) for
      this effect dropped to approximately 3 mM. 6. Tension responses evoked by
      caffeine in the absence of P(i) were smaller and slower to peak if fibres were
      exposed to P(i) in a restricted myoplasmic Ca2+ pool after SR Ca2+ loading. This
      indicated that myoplasmic P(i) can decrease and prolong the rate of Ca2+ release
      from the SR.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7730978
TI  - cAMP accelerates the decay of stretch-activated inward currents in guinea-pig
      urinary bladder myocytes.
AB  - 1. Myocytes from the urinary bladder were stretched longitudinally by 5-20%. At 
      50 mV, stretch induced whole-cell inward currents (Iin) between -100 and -600 pA.
      Iin decayed slowly with time to 93 +/- 20% (mean +/- S.E.M., n = 6) of the
      initial value in 1 min. The mechanisms of this 'adaptation' and its modulation by
      dibutyryl cAMP (dBcAMP) were analysed with whole-cell and single channel
      currents. 2. When the cells were internally perfused with 100 microM 8-bromo-cAMP
      (8BrcAMP), stretch induced an Iin of the usual amplitude that decayed completely
      within 40 +/- 13 s. When 200 microM dBcAMP was bath applied 10 s after the start
      of the stretch, Iin decayed to zero within 85 +/- 18 s. 3. dBcAMP increased the
      K+ current through Ca(2+)-activated BK channels (IK(Ca)) at 0 mV with a time
      course that correlated well with the decay of Iin, and block of IK(Ca) by TEA
      suppressed the dBcAMP-induced decay of Iin. In the presence of intracellular
      BAPTA, dBcAMP increased the stretch-induced Iin. The results suggest that
      adaptation is caused by superimposition of IK(Ca) which is increased through
      elevation of near-membrane [Ca2+] and by cAMP-dependent phosphorylation. 4.
      Single channel analysis was carried out with 140 mM KCl electrode solution and at
      -50 mV. Stretch-activated channels (SACs) were recorded during pulses of negative
      pressures between -2 and -5 kPa. Activity (NPo) of SACs was constant for at least
      4 min, e.g. evidence for adaptation was missing. dBcAMP (200 microM) increased
      NPo of SACs by 142 +/- 35% (n = 16). 5. dBcAMP increased NPo via frequency of
      openings and channel open time. In five of sixteen patches, dBcAMP induced
      openings without suction. Similar effects were induced by the catalytic subunit
      of cAMP-dependent protein kinase (PKAc), applied to inside-out patches. 6. NPo,
      normalized by its maximum, increased with more negative pressure along an S
      shaped curve. dBcAMP increased the sensitivity of SACs to stretch by shifting the
      point of half-maximal activity from -3.2 to -2.6 kPa. 7. The augmentation of NPo
      by dBcAMP is attributed to the phosphorylation of SACs promoting their opening.
      Adaptation of Iin is discussed as a 'secondary' effect of stretch-activated
      channels: Ca2+ influx through SACs increases the Ca2+ concentration that
      activates BK channels whose Ca2+ sensitivity is increased by cAMP.

PMID- 7730979
TI  - Veratridine-induced oscillations of cytosolic calcium and membrane potential in
      bovine chromaffin cells.
AB  - 1. Veratridine (VTD) induced large oscillations of the cytosolic Ca2+
      concentration ([Ca2+]i) and the membrane potential (Vm) in otherwise silent
      bovine chromaffin cells loaded with fura-2. 2. Depletion of the intracellular
      Ca2+ stores by thapsigargin or ryanodine did not affect these oscillations.
      Caffeine had a complex effect, decreasing them in cells with high activity but
      increasing them in cells with low activity. 3. The [Ca2+]i oscillations required
      extracellular Ca2+ and Na+ and were blocked by Ni2+ or tetrodotoxin. They were
      antagonized by high external concentrations of Mg2+ and/or Ca2+. 4. The
      oscillations of Vm had three phases: (i) slow depolarization (20 mV in 10-40 s);
      (ii) further fast depolarization (30 mV in 1 s); and (iii) rapid (5 s)
      repolarization. [Ca2+]i decreased during (i), increased quickly during (ii) with
      a 1 s delay with regard to the peak depolarization, and decreased during (iii).
      5. Slight depolarizations increased the frequency of the oscillations whereas
      large depolarizations decreased it. 6. The Ca(2+)-dependent K+ channel blocker
      apamin increased the duration and decreased the frequency of the oscillations. 7.
      We propose the following mechanism for the oscillations: (i) the membrane
      depolarizes slowly by a decrease of potassium conductance (gK), perhaps due to a
      gradual decrease of [Ca2+]i; (ii) the threshold for activation of Na+ channels
      (decreased by VTD) is reached, producing further depolarization and recruiting
      Ca2+ channels, and inactivation of both Ca2+ and VTD-poisoned Na+ channels is
      slow; and (iii) gK increases, aided by activation of Ca(2+)-dependent K+ channels
      by the increased [Ca2+]i, and the membrane repolarizes. The contribution of the
      Na+ channels seems essential for the generation of the oscillations. 8. Bovine
      chromaffin cells have the machinery required for [Ca2+]i oscillations even though
      the more physiological stimulus tested here (high K+, field electrical
      stimulation, nicotinic or muscarinic agonists) produced mainly non-oscillatory
      responses.

PMID- 7730980
TI  - Fusimotor neurone responses to medial plantar nerve stimulation in the
      decerebrate cat.
AB  - 1. The effect of single shock electrical stimulation, up to 20 x threshold (T),
      of the medial plantar nerve on the discharges of single medial gastrocnemius
      static and dynamic gamma-efferents has been investigated in the decerebrate cat.
      2. The neurones were classified as static (15) or dynamic (8) indirectly on the
      basis of their locomotor and/or resting discharge characteristics. 3. All gamma
      efferents were affected by stimulation of the medial plantar nerve. Dynamic units
      showed net inhibition while facilitation dominated the responses of static
      neurones. 4. The responses of dynamic units consisted of powerful short latency
      (15 +/- 1.2 ms, mean +/- S.D.) spinal inhibition followed by weaker facilitation
      that was difficult to characterize due to concomitant rephasing of neuronal
      discharge. 5. Static neurones showed two patterns of response. Some units (7 of
      15) were facilitated at medium latency (39.9 +/- 12.2 ms) while the remainder
      showed mixed effects in which short latency (18 +/- 3.6 ms) spinal inhibition was
      followed by stronger facilitation (latency, 38.1 +/- 5.3 ms). 6. Fusimotor
      facilitation and inhibition were generally present at 2T. The inhibition of
      dynamic and static gamma-efferents, and the facilitation of the latter type,
      increased with stimulus intensity. Thus low and high threshold afferents
      contributed to the effects without changing their qualitative nature. 7. We
      conclude that low threshold cutaneous mechanoreceptors in the plantar surface of
      the foot are capable of influencing the discharges of medial gastrocnemius static
      and dynamic gamma-efferents. Further, the cutaneous responses of fusimotor
      neurones appear to vary according to both the source of the afferent input and
      the type of unit involved. 8. The results are discussed in relation to the
      control and function of fusimotor neurones and the possible existence of
      subdivisions within the static system.

PMID- 7730981
TI  - Stimulation of guinea-pig tracheal afferent fibres by non-isosmotic and low
      chloride stimuli and the effect of frusemide.
AB  - 1. Inhalation of low-chloride or non-isosmotic solutions evokes cough or reflex
      bronchoconstriction in humans that is inhibited by frusemide (furosemide), whilst
      capsaicin-evoked cough is unaffected. Here we have examined the responses of
      single vagal afferent fibres innervating the isolated guinea-pig trachea to these
      stimuli, and tested the effect of frusemide on fibre responses. 2. Both distilled
      water and hypertonic saline applied for 30 s onto identified receptive fields
      produced marked excitation of all A delta and C fibres tested. Isotonic glucose,
      a low-chloride solution, was a less potent stimulant and caused excitation in 37%
      of A delta fibres and 69% of C fibres. There was no difference in the
      distribution of low-chloride sensitive and insensitive receptive fields. 3. In
      the presence of frusemide, responses of A delta fibres to isotonic glucose were
      significantly inhibited to 34.2 +/- 6.2% of the pre-drug control level. However,
      frusemide was without effect either on responses of A delta fibres to distilled
      water or hypertonic saline, or on responses of C fibres to capsaicin. 4. These
      data support a role for tracheo-bronchial A delta and C fibres in airway reflexes
      evoked by hypotonic, hypertonic and low-chloride stimuli. The protective effect
      of frusemide against airway responses to low-chloride but not to non-isosmotic
      solutions may reflect an action on sensory nerve endings.

PMID- 7730982
TI  - Variations of blood flow at optic nerve head induced by sinusoidal flicker
      stimulation in cats.
AB  - 1. The present investigation explored, in thirty-four anaesthetized cats, the
      blood flow changes at the optic nerve head elicited by sinusoidally modulated
      photic stimuli. 2. The stimuli were achromatic, diffuse and had 30 deg diameter
      field size; the stimulus frequency was varied from 0 to 100 Hz, modulation depth
      from 0 to 100% and mean retinal illuminance up to 50,000 trolands (td); the blood
      flow was measured with a near-infrared (810 nm) laser Doppler flowmeter. 3. At
      various frequencies, modulation depths and mean retinal illuminance, sinusoidal
      flicker stimulation always caused an increase in blood flow at the optic nerve
      head relative to steady stimulation. 4. The frequency response and temporal
      contrast sensitivity function of the blood flow changes had a bandpass shape; the
      high-frequency slope of the frequency response was 3 decades (dec) per decade and
      that of the temporal contrast sensitivity function was 1.7 dec per dec, close to
      the slope for cat 'on' ganglion cells (2.6 dec per dec). 5. In most cats, the
      magnitude of the increase in blood flow was a sigmoidal function of modulation
      depth; in the remainder, the relationship was close to linear. 6. The threshold
      of blood flow changes varied with respect to mean retinal illuminance similar to
      Ferry-Porter's law and the photopic linear slope was 50 Hz dec-1. 7. In
      comparison with reported psychophysical and electrophysiological responses
      elicited by similar stimulations, the results of the present study resemble more
      those obtained from ganglion cells than those from electroretinograms, visual
      evoked potentials and psychophysics. It is suggested that the blood flow changes
      at the optic nerve head are induced by the activity of ganglion cells.

PMID- 7730983
TI  - The effects of thyroid hormones on oxygen and glucose metabolism in the sheep
      fetus during late gestation.
AB  - 1. The effects of thyroid hormones on fetal metabolism during late gestation were
      examined by measuring the rates of glucose and oxygen utilization rates in
      chronically catheterized sheep fetuses made hypothyroid by either fetal
      thyroidectomy (TX) or hypophysectomy (HX). The values were compared with those in
      intact fetuses and in thyroxine (T4)-treated TX and HX fetuses. 2. Umbilical O2
      uptake expressed on a weight-specific basis was reduced by 20-30% in the
      hypothyroid fetuses and was restored to normal values when plasma T4 levels were
      maintained in the TX and HX fetuses by exogenous T4 administration. 3. The low O2
      consumption rates of the untreated hypothyroid fetuses were accompanied by fetal
      growth retardation, an abnormal blood gas status, and in the TX fetuses, by
      significant reductions in the rates of glucose oxidation, CO2 production from
      glucose carbon and O2 utilization for glucose oxidation. 4. When T4 levels were
      maintained in the TX fetuses, these metabolic rates and fetal blood gas status
      were restored to their normal values. Replacement of T4 also sustained growth in
      TX but not in HX fetuses. 5. When the data from all fetuses were combined
      irrespective of treatment, there were significant positive correlations between
      plasma levels of T4 (but not triiodothyronine (T3)) and the rates of umbilical O2
      uptake, glucose oxidation, CO2 production from glucose carbon and O2 utilization
      for glucose oxidation in the individual fetuses. 6. These findings demonstrate
      that T4 is a physiological regulator of O2 utilization by the sheep fetus close
      to term.

PMID- 7730984
TI  - After-effects on stiffness and stretch reflexes of human finger flexor muscles
      attributed to muscle thixotropy.
AB  - 1. While the subject maintained a weak contraction in his finger flexor muscles,
      holding the metacarpophalangeal joints in 45 deg flexion, test torque pulses were
      applied which caused rapid finger extension movements and electromyographic (EMG)
      stretch reflex responses. Before each test pulse the fingers were passively
      flexed or extended ('post-short' and 'post-long' trials) for about 10 s. The EMG
      and joint deflection responses in the two types of trial were compared after
      averaging. 2. In the 'post-long' trials, the EMG reflex response showed a
      comparative increase in latency, with a reduction of the short-latency (M1)
      component and an enhancement of the medium-latency (M2) component. 3. The angular
      deflections were larger, and the turning points of the deflections, which
      indicated the start of the mechanical reflex responses, occurred later in the
      'post-long' trials. These differences were not seen when the torque pulse was
      immediately preceded by a strong, brief isometric finger flexor contraction in
      the test position. 4. Immediately following the return to the test position the
      background finger flexor EMG activity was larger in the 'post-long' trials, a
      difference which gradually subsided over 15-20 s. A strong, brief contraction in
      the test position also eliminated this inter-trial difference. 5. The results are
      interpreted as manifestations of thixotropic after-effects in intra- and
      extrafusal muscle fibres. It is proposed that the M1 component of the stretch
      reflex is largely a response to the 'initial burst' of impulses in primary
      spindle afferents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730985
TI  - Human muscle spindle afferent activity in relation to visual control in precision
      finger movements.
AB  - 1. Impulse activities of muscle spindle afferents from the finger extensor
      muscles were recorded in the radial nerve of human subjects. In addition to
      single unit activity, surface EMG was recorded as well as finger joint position
      and angular velocity. 2. All units were studied under two conditions of voluntary
      finger movements. In the visual condition, the subject tracked ramp and hold
      sequences at a single metacarpophalangeal joint. In the non-visual condition the
      subject was asked to produce the same movement while visual control was denied
      altogether. 3. With sixteen units, detailed statistical analyses failed to reveal
      significant differences in muscle spindle afferent activity between the visual
      and the non-visual task. However, with two group Ia units, impulse rate was
      marginally but significantly higher in the visual task even when differences in
      average movement velocity, velocity variability and EMG level had been factored
      out. 4. The findings suggested that access to visual information for movement
      control did not produce any large-scale differences in spindle afference,
      although a small effect of an increased and independent gamma-activation emerged
      in the statistical analysis in 11% of the units.

PMID- 7730986
TI  - Sensory origin of lobeline-induced sensations: a correlative study in man and
      cat.
AB  - 1. Intravenous injections of lobeline HCl into twenty-six normal young male human
      volunteers produced sensations of choking, pressure or fumes in the throat and
      upper chest at a mean threshold dose of 12 micrograms kg-1. 2. Reflex changes in
      breathing pattern usually appeared just before the sensations. Increasing the
      dose of lobeline increased the intensity of the sensations gradually until a dry
      cough appeared at a mean threshold dose of 24.3 micrograms kg-1. At these doses
      there was a mean difference of 0.3s in the latencies for sensation and
      respiratory reflex; in four subjects there was no difference at all. 3. In cats
      anaesthetized with 35 mg kg-1 sodium pentobarbitone, injecting 25-67 micrograms
      kg-1 lobeline into the right atrium sensitized thirteen out of seventeen rapidly
      adapting receptors (RARs). In three out of four cats lobeline had no excitatory
      effect on the RARs in the absence of normal activity (i.e. when it was injected
      while artificial respiration was suspended), but on restarting the respiration
      the activity increased greatly. After injecting lobeline, the activity increased
      during inflation or deflation or in both phases of the respiratory cycle. It also
      increased greatly during deflation produced by suction of air from the lungs
      after lobeline. Such presumed increased activity in the RARs of man produced by
      forced expiration to residual volume at the time lobeline-induced sensations were
      expected did not enhance the sensations in any subject. 4. In all the subjects
      tested, forced expiration alone, which should stimulate RARs, never produced a
      dry cough or sensations similar to those produced by lobeline.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7730987
TI  - Primary afferent-evoked glycine- and GABA-mediated IPSPs in substantia gelatinosa
      neurones in the rat spinal cord in vitro.
AB  - 1. The possible roles of glycine and gamma-aminobutyric acid (GABA) as inhibitory
      transmitters in the spinal dorsal horn were studied by intracellular recordings
      from substantia gelatinosa (SG) neurones in transverse slices of the adult rat
      spinal cord which retained an attached dorsal root. 2. Stimulation of primary
      afferent A delta fibres evoked an initial excitatory postsynaptic potential (fast
      EPSP) followed by a short and/or long inhibitory postsynaptic potential (short
      and long IPSP). The short IPSP, observed in twenty-nine SG neurones (37%) which
      received inhibitory inputs, had a mean latency of 3.6 ms and a half-decay time of
      11 ms, while the long IPSP had a mean latency of 3.7 ms and a half-decay time of
      42 ms and was observed in thirty-seven SG neurones (47%). The remaining twelve
      neurones (16%) exhibited both short and long IPSPs. Both IPSPs reversed polarity
      at a membrane potential of -70 +/- 4 mV. The short IPSP was reversibly blocked by
      the glycine receptor antagonist strychnine (0.5-2 microM), while the long IPSP
      was reversibly blocked by the GABAA receptor antagonist bicuculline (10-20
      microM). 3. In the majority of SG neurones, the short and long IPSPs appeared to
      be disynaptic and were blocked by the non-N-methyl-D-aspartic acid (non-NMDA)
      receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5-10 microM).
      Both IPSPs were less sensitive (depressed by less than 30%) to the NMDA receptor
      antagonist DL-2-amino-5-phosphonovaleric acid (APV; 50-100 microM). 4. In ten SG
      neurones (13%), bath-applied glutamate (0.5-2 mM) increased the amplitude and
      frequency of IPSPs, which had a similar time course to that of the short IPSP
      evoked by afferent A delta fibres. The glutamate-induced short IPSPs were blocked
      by tetrodotoxin (0.5 microM) or strychnine (0.5-1 microM). In twelve neurones
      (16%), glutamate hyperpolarized the membrane or increased the amplitude and
      frequency of IPSPs that had a similar time course to that of the A delta fibre
      evoked long IPSPs. The glutamate-induced membrane hyperpolarization and long
      IPSPs decreased in amplitude with membrane hyperpolarization and reversed
      polarity at -70 +/- 6 mV. These hyperpolarizing responses were blocked by
      tetrodotoxin (0.5 microM) or bicuculline (10 microM). 5. These observations
      suggest that primary afferent A delta fibres activate glycinergic and/or
      GABAergic interneurones primarily through the non-NMDA receptor subclass and
      result in inhibition of nearby SG neurones in the dorsal horn of the spinal
      cord.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7730988
TI  - Synaptic potentiation of dual-component excitatory postsynaptic currents in the
      rat hippocampus.
AB  - 1. Whole-cell patch-clamp recording has been used to study tetanus-induced
      synaptic potentiation of dual-component excitatory postsynaptic currents (EPSCs)
      in the CA1 region of rat hippocampal slices, following blockade of GABAA and
      GABAB receptor-mediated synaptic inhibition. 2. At a holding potential of -60 mV,
      the initial slope of the EPSC (between 10 and 60% of maximum amplitude) provided
      an accurate measurement of the AMPA receptor-mediated component, and the
      amplitude of the EPSC at a latency of 100 ms provided the best estimate of the
      size of the NMDA receptor-mediated component. 3. Neurons were voltage clamped for
      at least 45 min prior to delivery of a tetanus (test intensity, 100 Hz, 1 s).
      Measurements at 10 and 30 min following the tetanus were used as indications of
      short-term potentiation (STP) and long-term potentiation (LTP), respectively. One
      set of neurons were voltage clamped at -60 mV throughout. These neurons could be
      subdivided into two populations on the basis of whether or not there was LTP (n =
      9), or only STP (n = 6), of the AMPA receptor-mediated component. A second set of
      neurons were voltage clamped at -60 mV for 30 min and then at -50 mV for 15 min
      before, during and for 30 min following tetanization. In these experiments there
      was STP but not LTP (n = 8). 4. In all neurons (n = 23), the time course of the
      potentiation of the NMDA receptor-mediated component paralleled that of the AMPA
      receptor-mediated component. In addition, potentiation of the NMDA and AMPA
      receptor-mediated components were of a similar magnitude. 5. These data
      demonstrate that it is possible to induce LTP by high frequency stimulation after
      45 min of whole-cell recording. Under these conditions, there is a parallel
      potentiation of the AMPA and NMDA receptor-mediated components of dual-component
      EPSCs. This constitutes the first evidence, from studies of dual-component
      synaptic responses, which is consistent with a presynaptic locus of expression of
      tetanus-induced STP and LTP in the hippocampus.

PMID- 7730989
TI  - NMDA receptor-mediated sympathetic chemoreflex excitation of RVL-spinal vasomotor
      neurones in rats.
AB  - 1. We investigated the role of N-methyl-D-aspartic acid (NMDA) receptors in
      mediating hypoxic excitation of the reticulospinal vasomotor neurones of the
      rostroventrolateral reticular nucleus (RVL) of the medulla oblongata in paralysed
      ventilated rats. 2. Unilateral close arterial injection of sodium cyanide (100
      nmol) into the carotid sinus region or ventilation with 100% N2 for 12 s rapidly,
      reversibly and reproducibly excited the RVL-spinal vasomotor neurones, followed
      about 1-2 s later by increases in sympathetic nerve activity and arterial
      pressure, effects abolished by denervation of the ipsilateral carotid sinus
      nerve. 3. Ionophoresis onto the RVL-spinal vasomotor neurones of kynurenate (a
      wide-spectrum antagonist of the excitatory amino acid receptors) or of 2-amino-5
      monophosphovaleric acid (APV; a selective NMDA receptor antagonist), but not of
      xanthurenate (an inactive analogue of kynurenate), blocked the excitation
      elicited by intracarotid cyanide or 12 s of hypoxia. Kynurenate completely and
      APV partially blocked the excitatory responses to ionophoretically applied L
      glutamate. APV, however, did not alter the excitatory responses of the vasomotor
      neurones to ionophoreses of kainate and quisqualate. 4. Bilateral microinjection
      of kynurenate (10 nmol, 50 nl per site) or APV (5 nmol, 50 nl per site) into the
      RVL blocked the increases in arterial pressure elicited by intracarotid cyanide
      or 12 s of 100% N2 ventilation. 5. Twenty seconds of intratracheal administration
      of 100% N2 resulted in complex and prolonged elevations of arterial pressure, the
      late component of which was affected neither by sinus denervation nor by
      microinjections of kynurenate or APV into the RVL. 6. We conclude that the
      sympathetic and cardiovascular responses to stimulation of arterial
      chemoreceptors result from excitation of RVL-spinal vasomotor neurones via
      activation of the NMDA subtypes of the excitatory amino acid receptors of the
      neurones. In contrast, the failure of these antagonists to influence the delayed
      excitation of the RVL-spinal vasomotor neurons by more prolonged exposure to N2
      inhalation further supports the view that these neurones are directly stimulated
      by hypoxia.

PMID- 7730990
TI  - Presynaptic actions of morphine: blockade of cholecystokinin-induced
      noradrenaline release in the rat supraoptic nucleus.
AB  - 1. This study aimed to establish the site at which morphine acts to inhibit
      oxytocin release in response to peripheral administration of cholecystokinin
      (CCK). 2. Conscious rats were given morphine or vehicle followed by CCK or
      vehicle (I.V.). Fos immunoreactivity was apparent 90 min after CCK injection in
      the supraoptic nucleus of vehicle- but not morphine-pretreated animals. 3. In the
      dorsomedial (C2/A2) and the ventrolateral (C1/A1) regions of the brainstem, about
      half of the cells immunoreactive for tyrosine hydroxylase (TH) expressed Fos-like
      protein after CCK injection. In the C2/A2 region, 20% of the Fos-positive cells
      also showed TH immunoreactivity, whereas in the C1/A1 region 68% did so. Morphine
      treatment did not significantly change the number of cells expressing Fos
      immunoreactivity, or the percentage of TH-positive cells expressing Fos-like
      protein. 4. Amine release was measured in the supraoptic nucleus of urethane
      anaesthetized rats using a microdialysis probe. An I.V. injection of CCK
      increased the concentrations in the dialysate of noradrenaline and serotonin, but
      not of either adrenaline or dopamine. Pretreatment with morphine (I.V.) blocked
      the effects of CCK in a naloxone-reversible manner. 5. Inclusion of morphine in
      the dialysate also blocked the increase in noradrenaline and serotonin in
      response to CCK in a naloxone-reversible manner. 6. These observations indicate
      that morphine acts near or within the supraoptic nucleus to block CCK-evoked
      noradrenaline release presynaptically. This presynaptic action of morphine may be
      a cause of the blockade of oxytocin release after CCK.

PMID- 7730991
TI  - Potentiation of Ca2+ transients in the presynaptic terminals of goldfish retinal
      bipolar cells.
AB  - 1. To study a possible contribution of intracellular Ca2+ stores to the
      presynaptic Ca2+ regulation, the Ca2+ current (ICa) and the intracellular free
      Ca2+ concentration ([Ca2+]i) were simultaneously monitored in isolated goldfish
      retinal bipolar cells using the whole-cell voltage clamp procedure and fura-2
      fluorimetry. 2. The Ca2+ transient triggered by the activation of ICa was
      potentiated when [Ca2+]i was increased by applying either a prepulse or a small
      steady depolarization. The potentiation seemed to be partly due to the release of
      Ca2+ from intracellular Ca2+ stores. 3. The intracellular Ca2+ release was
      reversibly inhibited by caffeine but was not affected by ryanodine, suggesting
      that Ca2+ is released through intracellular Ca2+ channels which differ from
      ryanodine receptor channels. 4. These results suggest that the intracellular Ca2+
      release may contribute to the facilitation of transmitter release.

PMID- 7730992
TI  - Down-regulation of A1 adenosine receptors coupled to muscarinic K+ current in
      cultured guinea-pig atrial myocytes.
AB  - 1. Muscarinic K+ current (IK(ACh)) was measured in cultured atrial myocytes from
      hearts of adult guinea-pigs using whole-cell voltage clamp. IK(ACh) was activated
      by superfusion with solutions containing either acetylcholine (ACh) or adenosine
      (Ado), in saturating concentrations of 2 microM (ACh) and 1 mM (Ado),
      respectively. 2. In freshly isolated cells the amplitude of the current activated
      by Ado (IK(Ado)) was 58% (mean) of the current that was induced by ACh. In serum
      free culture this relation, but also the absolute density of IK(ACh), remained
      fairly constant for up to 8 days. 3. If the culture medium was supplemented with
      fetal calf serum (FCS, 5%) the relation IK(Ado)/IK(ACh) gradually decayed,
      reaching a value of less than 0.1 on days 7-8, whereas the response to ACh
      remained stable over this period of time. 4. After treatment of cells with FCS
      containing medium, no recovery was observed upon FCS withdrawal for up to 4 days.
      5. The effect of FCS on responsiveness to Ado was half-maximal at about 1% (v/v).
      The active principle can be dialysed (mol. mass exclusion: 10 kDa). It is not
      identical with an albumin-associated factor that has been shown to be a potent
      activator of atrial IK(ACh) upon acute superfusion. Loss of responsiveness to Ado
      was paralleled by a reduction of binding sites to the A1 adenosine receptor
      specific radioligand 8-cyclopentyl-1,3-dipropylxanthine ([3H]CPX). 6. It is
      concluded that FCS contains a factor that causes down-regulation of A1 Ado
      receptors. The signalling pathway that leads to an increased opening activity of
      IK(ACh) channels and other receptors, such as the M2 muscarinic receptor, linked
      to this signalling pathway are not affected by this factor.

PMID- 7730994
TI  - Communicating in hypertension. Proceedings of a symposium of the World
      Hypertension League. Padova, Italy, 2-3 December 1993.

PMID- 7730993
TI  - The effects of mechanical loading and changes of length on single guinea-pig
      ventricular myocytes.
AB  - 1. The effects of mechanical loading and changes of length on the contraction of
      single guinea-pig ventricular myocytes has been investigated. 2. Cell shortening
      was monitored during isotonic contractions (in which the cell shortened freely)
      and after attaching carbon fibres of known compliance to the ends of the cell, so
      that the cell contracted auxotonically (the cell both shortened and developed
      force). 3. Mechanically loading the cells decreased the amount of shortening
      during a contraction and abbreviated the contraction. There were, however, no
      consistent changes in the action potential or the [Ca2+]i transient (measured
      with the fluorescent dye fura-2). 4. Increasing stimulation rate increased the
      size of the contraction and the [Ca2+]i transient in both isotonic and auxotonic
      conditions. The increase in the size of the contraction induced by an increase in
      stimulation rate was greater in auxotonic conditions but the increase in the size
      of the [Ca2+]i transient was not. 5. When cells were stretched, there was a step
      increase in the size of the contraction and a prolongation of its time course.
      However, neither the size nor the time course of the accompanying [Ca2+]i
      transient was significantly altered by this intervention. 6. When a stretch was
      maintained, a further, slow increase in the size of the contraction occurred
      during the following 3-11 min, in about half the cells studied. The probability
      of this slow response occurring was increased if the initial degree of activation
      of the cell was decreased. 7. These data suggest that the mechanisms underlying
      the responses to mechanical loading and changes of length are the same in both
      multicellular and single cell preparations of cardiac muscle.

PMID- 7730995
TI  - Communication and the media: health and public messages.

PMID- 7730996
TI  - Patient education: an example of one-to-one communication.
AB  - One fourth of a physician's office time is used on average for giving
      information, instructing and counselling. Such patient education takes place
      mostly in a one-to-one situation where the physician helps his patients to
      understand and accept their illnesses, to recognise and acknowledge risk
      behaviours, to make informed treatment decisions, to develop treatment plans, and
      to cope with problems of maintenance and relapse. The physician must be able to
      communicate with his patient in a way that fosters the patient's learning and
      change processes, in order to maximise the medical outcomes and hence the
      efficacy and effectiveness of his work. Unfortunately the immense therapeutic
      potential of patient education is still underutilised, in spite of the fact that
      patient education has a clearly proven impact on health outcomes, such as
      reducing morbidity and mortality, reducing risk behaviors and risk factors,
      increasing healthy behaviour as well as patient and doctor satisfaction, and
      avoiding malpractice litigation. This paper reviews the principles of motivation
      and doctor-patient communication, presents current models of the patient's
      learning and change process, derives rules for effective educational
      communication, and methodological advice for the individual patient education
      session.

PMID- 7730997
TI  - Communicating in hypertension: the potential role of television in Brazil.

PMID- 7730998
TI  - An analysis of the hypertension journals.
AB  - There are now at least nine medical journals which are exclusively related to the
      topic of hypertension, of which two started publication in 1992. We have
      conducted an analysis of the impact of these journals in the published body of
      medical research into hypertension as well as the reports published in 1993 by
      the hypertension management 'guidelines' committees in the UK, USA, New Zealand,
      Canada and the WHO. Finally an analysis was conducted of the contents of the four
      established hypertension journals (Hypertension, Journal of Hypertension, Journal
      of Human Hypertension and American Journal of Hypertension) in 1992 in relation
      to the country of origin of the papers and the topics covered. Only 19% of all
      the hypertension papers listed in Index Medicus in 1992 were from the four
      established journals and only 12.6% of papers quoted in the 'guidelines' reports
      were from these journals. Most papers, and particularly the important ones, tend
      to be published in the weekly or monthly general medical journals. In the
      contents of the four journals, Hypertension and Journal of Hypertension tended to
      take more papers devoted to basic science than the Journal of Human Hypertension
      and American Journal of Hypertension which favoured more clinically relevant
      papers. American papers tended to go to American journals while European and
      Japanese papers appeared in all journals, although the Japanese bias towards
      basic science meant that their contributions also appeared in the two basic
      science orientated journals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7730999
TI  - Guidelines and consensus statements: their use and impact.

PMID- 7731000
TI  - Patient-doctor interactions in hypertension.
AB  - The interaction between doctors and their hypertensive patients still suffers
      from a number of shortcomings owing to ignorance and misconceptions on both sides
      as well as poorly defined mutual goals. In this paper, an attempt is made to
      define common goals of doctors and patients and to describe the information
      status of both the patient and the doctor concerning the disease. Problems
      associated with the management/treatment of hypertension for patient and doctor
      are addressed, and expectations, attitudes and considerations on 'both sides of
      the needle' are discussed. Finally, the individual concern of patients and
      doctors with anti-hypertensive drug treatment is related to frequent problems
      such as inadequate drug selection on the doctor's side or non-compliance on the
      patient's side.

PMID- 7731001
TI  - Patient Education Project: a joint WHO-WHL undertaking--experience from Hungary.

PMID- 7731002
TI  - Communication theory and the search for effective feedback.
AB  - If messages transmitted to the public, patients and health professionals could be
      assured of being received, understood and acted on as intended by the senders of
      messages, there would be little need to focus on communications and feedback.
      That the physician's office, the healthcare system and the community are littered
      with messages that 'never got through' attests to the problem of ineffective
      communications and the absence of effective feedback. Communication theorists,
      health psychologists and thoughtful health professionals, particularly those
      working in community hypertension programmes, have developed approaches that
      improve the probabilities of 'getting the message through'. Theory-based
      communications with built-in feedback and 'feed-forward' enhance the
      probabilities of success considerably. This presentation explores these problems
      using the SMCR model of communication. Differences between linear models and
      transactional models are discussed. On the assumption that the health message
      environments of the future will be increasingly complex with highly
      differentiated target audiences in a rapid paced computer and electronically
      driven world, 'getting the message through' will become an even greater challenge
      than in the recent past. Specific steps to change communication approaches in
      this setting are proposed.

PMID- 7731003
TI  - National High Blood Pressure Education Programme using data to focus
      communications to minority populations.

PMID- 7731004
TI  - Communication with the population: the North Karelia Project experience.

PMID- 7731005
TI  - Teaching communication skills: part of medical education?
AB  - Hypertension is generally a symptomless disease, but it needs lifelong treatment
      in most cases. This places enormous demands on individual doctors treating
      individual patients. Communication under these circumstances should be a skillful
      blend of patient education (for example about lifestyle, other risk factors,
      reasons for treatment) coupled with the development of a strong personal interest
      in, and relationship with, the patient in order to motivate that patient to
      follow advice and therapy. Communication skills in medicine are learnt slowly and
      often only by experience. Medical school deans are under enormous pressure to add
      extra items into an already crowded curriculum, and so education in communication
      tends to have a low priority. Before a school can take such interest in educating
      students in communication it first has to take an interest in the education of
      its teachers. Rather belatedly, medical schools are now taking such an interest.
      Previously academic promotion depended mainly on research publications and public
      profile and little on an assessment of an ability to teach. Increasingly both
      undergraduate and postgraduate teaching is now subject to assessment from those
      taught, and universities are now making formal assessments of their teachers'
      ability in communication. In Oxford all newly appointed teachers are asked to
      appear before a panel, give a short 10-15 min communication and to listen to
      criticism of their technique. Video filming of their performance is a valuable
      feedback in getting lecturers to see their own faults and to help improve their
      techniques. It is very important to begin such training not only at lecturer
      level but also at student level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731006
TI  - Workshop I: Communicating with the public.

PMID- 7731007
TI  - Workshop II: Doctor-patient communication.

PMID- 7731008
TI  - Workshop III: Communicating among health professionals--including health
      politicians.

PMID- 7731009
TI  - Workshop IV: Teaching communication in medical schools.

PMID- 7731010
TI  - Discovery of a novel series of orally active non-peptide endothelin-A (ETA)
      receptor-selective antagonists.

PMID- 7731011
TI  - 4,4-Disubstituted piperidines: a new class of NK1 antagonist.

PMID- 7731012
TI  - Farnesyl derivatives of rigid carboxylic acids-inhibitors of ras-dependent cell
      growth.
AB  - Inhibitors of the enzyme that methylates ras proteins, the prenylated protein
      methyltransferase (PPMTase), are described. They are farnesyl derivatives of
      rigid carboxylic acids that recognize the farnesylcysteine recognition domain of
      the enzyme but do not serve as substrates. They also inhibit ras-dependent cell
      growth by a mechanism that is probably unrelated to inhibition of ras
      methylation, even though their potencies as PPMTase inhibitors and cell-growth
      inhibitors correlate well. The most potent inhibitor is S-trans,trans
      farnesylthiosalicylic acid (FTS) (2). FTS (2) selectively inhibits the growth of
      human Ha-ras-transformed Rat1 cells in vitro (EC50 = 7.5 microM).

PMID- 7731013
TI  - New (2-methoxyphenyl)piperazine derivatives as 5-HT1A receptor ligands with
      reduced alpha 1-adrenergic activity. Synthesis and structure-affinity
      relationships.
AB  - New 2-(methoxyphenyl)piperazine derivatives 1 and 2 containing a terminal
      heteroaryl or cycloalkyl amide fragment were prepared and their 5-HT1A affinities
      evaluated by radioligand binding assays. The influence of the alkyl chain length
      or the amide group on affinity was evaluated. A four-carbon chain appears to be
      optimal when the amide fragment is a heteroaryl group. Derivatives with a
      cycloalkyl moiety displayed maximum affinity in the two methylene chain series.
      Electronic distribution within the amide region seems to have an influence on
      affinity in heteroaryl derivatives. Replacement of the heteroaryl moiety by a
      cycloalkyl group led to compounds with enhanced affinity. Increasing the
      lipophilicity of the cycloalkyl derivatives by annelation and/or saturation
      increased their affinity for the 5-HT1A sites. Compounds with cis
      bicyclo[3.3.0]octane (2a, 2c), norbornane (2f, 2g), and norbornene (2h, 2i)
      groups bind at 5-HT1A sites with 2-10-fold higher affinity than NAN-190.
      Antagonist activity at alpha 1-adrenergic receptors was evaluated for compounds
      with high affinity at 5-HT1A sites. Compounds 2a, 2c, 2f, 2g, and 2h strongly
      bind (Ki = 0.12-0.63 nM) at 5-HT1A receptors and are devoid of antagonist
      activity at alpha 1-adrenergic receptors.

PMID- 7731014
TI  - N-substituted oxazolo[5,4-b]pyridin-2(1H)-ones: a new class of non-opiate
      antinociceptive agents.
AB  - A series of 1-(aminoalkyl)- and 1-[(4-aryl-1-piperazinyl)alkyl]oxazolo[5,4
      b]pyridin-2(1H)-one derivatives of oxazolo[5,4-b]pyridin-2(1H)-one, incorporating
      modifications to the length of the alkyl side chain and to the amino or 4-aryl-1
      piperazinyl substituents, were tested for safety and analgesic efficacy in mice
      and rats. Some compounds with 4-(substituted or nonsubstituted phenyl)-1
      piperazinyl substituents and a 3-4-carbon alkyl side chain had significantly
      greater analgesic activity than that of the oxazolo[4,5-b]pyridin-2(3H)-one
      analogs. To reduce the metabolic N-dealkylation of the piperazine observed in our
      previous work on oxazolo[4,5-b]-pyridin-2(3H)-ones, analogs of the most active
      compounds with steric hindrance on the alkyl side chain were prepared and tested.
      The compound with the maximal combination of safety and analgesic efficacy was 1
      [[4-(4-fluorophenyl)-1-piperazinyl]propyl]oxazolo[5,4-b]pyridin- 2(1H)-one
      (compound 3b), with ED50 values of 5.6 mg/kg po (mouse, phenylquinone writhing
      test) and 0.5 mg/kg po (rat, acetic acid writhing test). Compound 3b is a potent,
      rapid-acting, non-opioid, nonantiinflammatory analgesic with low acute toxicity
      and sustained effect.

PMID- 7731015
TI  - Synthesis and histamine H1 receptor agonist activity of a series of 2
      phenylhistamines, 2-heteroarylhistamines, and analogues.
AB  - New histamine derivatives characterized by a (substituted) aryl, heteroaryl,
      benzyl, or heteroarylmethyl substituent in the C2 position of the imidazole ring
      have been prepared from appropriate imidates or amidines, respectively, and 2-oxo
      4-phthalimido-1-butyl acetate (1). The compounds were screened as potential H1
      receptor agonists on the isolated guinea pig ileum. The 3-halogenated 2
      phenylhistamines (halogen = Br (35) and I (36)) were equipotent with histamine,
      while 2-(3-(trifluoromethyl)phenyl)histamine (2-[2-(3-(trifluoromethyl)phenyl)-1H
      imidazol-4-yl]ethanamine (39)) was significantly more potent than histamine (39:
      pD2 = 6.81, relative activity = 128%). The 2-substituted histamine analogues were
      partial H1 receptor agonists on the endothelium-denuded isolated guinea pig aorta
      with pEC50 values generally smaller than observed on the guinea pig ileum, but
      the rank order of potency was found to be similar. The contractile effects on
      guinea pig ileum and aorta, respectively, could be blocked concentration
      dependently by the H1 receptor antagonist mepyramine, yielding KB values for
      mepyramine in the nanomolar range. In vitro compounds 35 and 39 bound to
      [3H]mepyramine-labeled guinea pig cerebellar membranes with a pKi of 6.1 and 5.9,
      respectively. However, upon iv administration, 35 (3-100 mg/kg) and 39 (3-300
      mg/kg) failed to inhibit the binding of [3H]mepyramine to mouse cerebral cortex
      in vivo, thereby indicating that these histamine derivatives are not able to
      penetrate the blood-brain barrier. In functional in vitro studies on histamine
      H2, H3, and other neurotransmitter receptors the selectivity of 39 was found to
      be 2138 (H1:H2), > 64 (H1:H3), 1000 (H1:M3), 105 (H1:alpha 1), 708 (H1:beta 1),
      and 71 (H1:5HT2A). Thus compound 39 is the most potent and selective H1 receptor
      agonist reported so far. These results make meta-substituted 2-phenylhistamines,
      especially 2-(3-(trifluoromethyl)phenyl)- and 2-(3-bromophenyl)histamine (39 and
      35, respectively) valuable experimental tools for the selective stimulation of
      histamine H1 receptors and the study of H1 receptor-mediated functions.

PMID- 7731016
TI  - Quantitative binding site model generation: compass applied to multiple
      chemotypes targeting the 5-HT1A receptor.
AB  - We present enhancements to the Compass algorithm that automatically deduce
      interchemotype relationships and generate predictive quantitative models of
      receptor binding based solely on structure-activity data. We applied the
      technique to a series of compounds assayed for 5-HT1A binding. A model was
      constructed from 20 compounds of two chemotypes and used to predict the
      affinities and bioactive conformation of 35 new compounds, most of which had new
      underlying scaffolds and/or functional groups. The model's mean error of
      prediction was 0.5 log units (essentially the assay resolution), even on quite
      divergent series. The predictions are supported by an interpretable hypothesis
      for the binding determinants of the receptor and the geometric relationships of
      the chemotypes.

PMID- 7731017
TI  - Synthesis and evaluation of pharmacological and pharmacokinetic properties of
      monopropyl analogs of 5-, 7-, and 8-[[(trifluoromethyl)sulfonyl]oxy]-2
      aminotetralins: central dopamine and serotonin receptor activity.
AB  - In order to explore further the structure-activity relationships of serotonergic
      and dopaminergic ligands, a series of enantiopure 5-, 7-, or 8-triflate (-OTf)
      substituted 2-(monopropylamino)-tetralins have been synthesized and evaluated in
      in vitro binding and in vivo biochemical and behavioral assays in rats.
      Consequently, the 8-OTf-substituted compound R-(+)-6 was found to be a potent and
      selective 5-HT1A (5-hydroxytryptamine) receptor agonist inducing a full-blown 5
      HT syndrome in normal rats, while the corresponding 5-OTf-substituted compound S
      (-)-12 was found to be a preferential dopamine (DA) autoreceptor agonist. A
      partial 5-HT syndrome was also observed for S-(-)-12, while the corresponding R
      (+)-12 was found to be inactive at the DA and 5-HT receptors both in vitro and in
      vivo. Compounds 6 and 12 were found to be major urinary metabolites following
      oral administration of their dipropyl analogs (2 and 13, respectively). Thus 6
      was proposed to be the metabolite responsible for the full-blown 5-HT syndrome
      seen after oral (but not subcutaneous) administration of 2. Similarly, 12 was
      proposed to be the metabolite responsible for the partial 5-HT syndrome seen
      after oral (but not subcutaneous) administration of 13. The bioavailability of R
      (+)-6 (7.6 +/- 1.1%) appeared to be slightly lower than that of 2 (11.2 +/-
      5.2%), although the in vitro metabolism of R-(+)-6 appeared to be slower than
      that of 2. Therefore first-pass metabolism was not thought to be the reason for
      the lower bioavailability of R-(+)-6, as compared to 2.

PMID- 7731018
TI  - Tricyclic heteroaromatic systems. Synthesis and A1 and A2a adenosine binding
      activities of some 1-aryl-1,4-dihydro-3-methyl[1]benzopyrano[2,3-c] pyrazol-4
      ones, 1-aryl-4,9-dihydro-3-methyl-1H-pyrazolo[3,4-b]quinolin-4- ones, and 1-aryl
      1H-imidazo[4,5-b]quinoxalines.
AB  - The syntheses and A1 and A2a adenosine binding activities of some new 1-aryl-1,4
      dihydro-3-methyl[1]benzopyrano[2,3-c]pyrazol-4-ones, 1-aryl-4,9-dihydro-3-methyl
      1H-pyrazolo[3,4-b]-quinolin-4-ones, and 1-aryl-1H-imidazo[4,5-b]quinoxalines are
      reported. Some compounds show A1 adenosine receptor affinity and selectivity.
      Structure-activity relationships on these new classes of adenosine receptor
      ligands are defined.

PMID- 7731019
TI  - Electrophilic N-benzylnaltrindoles as delta opioid receptor-selective
      antagonists.
AB  - The N-benzyl group of N-benzylnaltrindole (1, BNTI), a potent and selective delta
      2 opioid receptor antagonist, was employed as a scaffold to hold electrophilic
      moieties (isothiocyanate and haloacetamide) in an effort to obtain selective
      affinity labels (2-4 and 8-11). The corresponding acetamide derivatives (5-7)
      also were synthesized to serve as nonelectrophilic controls. The o- and p
      isothiocyanates (2 and 4) and the haloamides (8-11) were selective delta opioid
      receptor antagonists in the mouse vas deferens (MVD) preparations, while the meta
      isomer 3 was a delta-selective full agonist (IC50 = 5 nM). The fact that the
      effect of 2 and 4 was found to increase as a function of time in MVD suggests a
      covalent mechanism for the wash resistant component. The m-isothiocyanate 3 was
      found to be a delta-selective and irreversible agonist in the MVD, and it is
      suggested that it may be covalently binding to an agonist recognition site. In
      the mouse abdominal stretch antinociceptive assay, compounds 2-4 and 9 were delta
      selective antagonists but exhibited delta 2/delta 1 selectivity ratios than that
      of BNTI.

PMID- 7731020
TI  - Discovery and structure-activity relationships of sulfonamide ETA-selective
      antagonists.
AB  - Random screening of compounds in an ETA receptor binding assay led to the
      discovery of a class of benzenesulfonamide ligands. Optimization led to the
      development of 5-amino-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamides
      which were functional antagonists. Structural features which were important to
      activity included a 1,5-substitution pattern on the naphthalene ring; a
      sulfonamide NH with a pK value < 7; an amine, preferably with alkyl substituents,
      at the 5-position; and methyl groups on both the 3- and 4-positions of the
      isoxazole.

PMID- 7731021
TI  - Picornavirus inhibitors: trifluoromethyl substitution provides a global
      protective effect against hepatic metabolism.
AB  - Several modifications of the oxazoline ring of WIN 54954, a broad spectrum
      antipicornavirus compound, have been prepared in order to address the acid
      lability and metabolic instability of this compound. We have previously shown
      that the oxadiazole analogue 3 displayed comparable activity against a variety of
      rhinoviruses and appeared to be stable to acid. A monkey liver microsomal assay
      was developed to examine the metabolic stability in vitro of both compounds, and
      it was determined that WIN 54954 displayed 18 metabolic products while 3 was
      converted to 8 products. Two major products of 3 were determined by LC-MS/MS to
      be monohydroxylated at each of the terminal methyl groups. Replacement of the
      methyl on the isoxazole ring with a trifluoromethyl group, while preventing
      hydroxylation at this position, did not reduce the sensitivity of the molecule to
      microsomal metabolism at other sites. However, the (trifluoromethyl)oxadiazole 9
      not only prevented hydroxylation at this position but also provided protection at
      the isoxazole end of the molecule, resulting in only two minor products to the
      extent of 4%. The major product was identified as the monohydroxylated compound
      23. The global metabolic protective effect of trifluoromethyl group on the
      oxadiazole ring was further demonstrated by examining a variety of analogues
      including heterocyclic replacements of the isoxazole ring. In each case, the
      trifluoromethyl analogue displayed a protective effect when compared to the
      corresponding methyl analogue.

PMID- 7731022
TI  - Synthesis and in vivo evaluation of prodrugs of 9-[2
      (phosphonomethoxy)ethoxy]adenine.
AB  - A number of esters and amides of the anti-HIV nucleotide analogue 9-[2
      (phosphonomethoxy)-ethoxy]adenine (1) have been synthesized as potential prodrugs
      and evaluated for oral bioavailability in mice. Dialkyl esters 17-20 were
      prepared via a Mitsunobu coupling of alcohols 8-11 with 9-hydroxypurine 12
      whereas (acyloxy)alkyl esters 25-33 and bis-[(alkoxycarbonyl)methyl] and
      bis(amidomethyl) esters 34-39 were obtained by reaction of 1 with a suitable
      alkylating agent. Phosphonodichloridate chemistry was employed for the
      preparation of dialkyl and diaryl esters 42-65, and bis(phosphonoamidates) 66 and
      67. Following oral administration to mice, most of the dialkyl esters 17-20 were
      well-absorbed and then converted to the corresponding monoesters, but minimal
      further metabolism to 1 occurred. Bis[(pivaloyloxy)methyl] ester 25 displayed an
      oral bioavailability of 30% that was 15-fold higher than the bioavailability
      observed after dosing of 1. Methyl substitution at the alpha carbon of the
      bis[(pivaloyloxy)methyl] ester 25 (33) increased the oral bioavailability of 1 to
      74%. Some of the diaryl esters also showed improved absorption properties in
      comparison with that of 1. In particular, the crystalline hydrochloride salt of
      diphenyl ester 55 was well-absorbed and efficiently converted to the parent
      compound with an oral bioavailability of 50%. On the basis of these results as
      well as the physicochemical properties of the prodrugs and their stability in
      mouse duodenal contents, the hydrochloride salt of diphenyl ester 55 was
      identified as the preferred prodrug of 1.

PMID- 7731023
TI  - Cephalosporin derivatives of doxorubicin as prodrugs for activation by monoclonal
      antibody-beta-lactamase conjugates.
AB  - The synthesis of a series of cephalosporin doxorubicin derivatives that differ
      with respect to the substituent at position 7 of the cephem nucleus is described.
      These compounds are designed as prodrugs of doxorubicin for activation by
      monoclonal antibody-beta-lactamase conjugates. The key step in the synthesis of
      this series of compounds involves the use of the phenylacetamido group as an
      enzymatically removable protecting group for the 7-amino group on the cephem. In
      vitro cytotoxicity assays with H2981 lung adenocarcinoma cells revealed that
      cephalosporin doxorubicin derivatives were all less toxic than the released drug.
      Prodrugs containing negatively charged groups in the side chain, such as the
      delta-carboxybutanamido derivative 4 and the alpha-sulfophenylacetyl derivative
      5, displayed the least cytotoxic activity and were 46- and 26-fold less toxic
      than doxorubicin, respectively. The efficiency of activation of all the prodrugs
      was evaluated in cytotoxicity assays on H2981 cells with the beta-lactamases from
      Enterobacter cloacae P99, Escherichia coli TEM-1, and Bacillus cereus (type II).
      In general, the E. cloacae enzyme was found to most rapidly activate the majority
      of these prodrugs. Phenylacetamido prodrug 2 and delta-carboxybutanamido prodrug
      4 were both activated in an immunospecific manner by L6-E. cloacae beta
      lactamase, a monoclonal antibody conjugate that binds to receptors on H2981 lung
      adenocarcinoma cells.

PMID- 7731024
TI  - Synthesis, absolute configuration, and enantioselectivity of antiretroviral
      effect of (R)-(-)- and (S)-(+)-cytallene. Lipase-catalyzed enantioselective
      acylations of (+/-)-N4-acylcytallenes.
AB  - Enantioselectivity of acylations of (+/-)-cytallene (1b), (+/-)-N4
      acetylcytallene (11a), (+/-)-N4-benzoylcytallene (11b), and (+/-)-N4-(9
      fluorenylmethoxycarbonyl)cytallene (11c) using vinyl butyrate or acetate
      catalyzed by lipases in organic solvents was investigated. Reactions with 1b,
      11a, and adenallene (1a) did not display a high enantioselectivity but all
      resulted in a predominant acylation of the (-)-enantiomers. Application of the
      Lowe-Brewster rule led to a tentative assignment of the R-configuration to all
      acylated products. Studies of the time course of acylation of (+/-)-N4
      benzoylcytallene (11b) in chloroform, tetrahydrofuran (THF), tetrahydropyran
      (THP), tetrahydrothiophene (THT), and dioxane with lipase PS30 and/or AK showed
      that the reaction in THF catalyzed by lipase AK was the most promising for
      resolution of 11b. Indeed, a large-scale acylation afforded, after separation and
      deprotection of intermediates 3e and 10d, (+)- and (-)-cytallene (3c and 2b) in
      high yield and enantioselectivity. Acylation of 11c in THF led also to formation
      of 3c and 2b in high enantioselectivity. Single crystal X-ray diffraction
      established the S-configuration of (+)-cytallene (3c), thus confirming the
      assignment made on the basis of Lowe-Brewster rule. An improved large-scale
      synthesis of (+/-)-cytallene (1b) is also described. The R-enantiomer 2b
      inhibited the replication of a primary human immunodeficiency virus (HIV-1)
      isolate in phytohemagglutinin-activated peripheral blood mononuclear cells (PHA
      PBM) with IC50 0.4 and IC90 1.7 microM. (+/-)-Cytallene (1b) exhibited IC50 0.8
      and IC90 3.4 microM. Both compounds completely suppressed replication of HIV-1 at
      10 microM with no detectable cytotoxicity. The S-enantiomer (3c) was inactive.

PMID- 7731025
TI  - The synthesis of N-hydroxy-N'-phenyloctanediamide and its inhibitory effect on
      proliferation of AXC rat prostate cancer cells.
AB  - We have developed a practical synthesis of N-hydroxy-N'-phenyloctanediamide from
      the methyl ester of suberanilic acid. It provides the product in high yield and
      purity with a simple purification process. We have found that at 10(-5) M it has
      a dramatic effect on T/5 AXC/SSh rat prostate cancer cells in vitro. It is a
      potent inhibitor of cell proliferation and it changes the cell morphology to
      resemble nonmalignant cells.

PMID- 7731027
TI  - Asian macaque pepsinogens and pepsins.
AB  - Five pepsinogens were purified from the gastric mucosa of eight species of Asian
      macaques. The chromatographic behavior of each pepsinogen was essentially the
      same but differed from human and other mammalian pepsinogens. The major
      pepsinogen in each species was pepsinogen A-1, accounting for 29-48% of the
      total. Amino acid compositions and some enzymatic properties of derived pepsins
      were similar for the various monkey species. This high degree of similarity
      confirms that these species are closely related to one another.

PMID- 7731026
TI  - Individualized gonadotropin regimens for follicular stimulation in macaques
      during in vitro fertilization (IVF) cycles.
AB  - Follicular stimulation was compared in macaques receiving sequential gonadotropin
      treatment which was terminated after seven, eight, or nine days depending on the
      time required to attain preselected criteria of follicular maturation. Although
      estradiol levels and follicle sizes varied, the number of follicles and
      oocytes/animal, oocyte nuclear maturity, IVF rates and progesterone levels during
      the luteal phase were similar among groups. Reducing the duration of gonadotropin
      treatment to individualize follicular stimulation regimens does not compromise
      follicle or gamete quality.

PMID- 7731028
TI  - The effect of serial passage on Sabin oral poliomyelitis vaccine virus in
      secondary monkey kidney versus Vero cells as measured by the monkey
      neurovirulence test.
AB  - The three Sabin strains of poliomyelitis seed virus were serially passaged in
      either secondary monkey kidney or Vero cell cultures and the tenth passage of
      each virus harvest compared to non-passaged Sabin reference virus of the same
      type using the monkey neurovirulence test. All three types were further
      attenuated by passage in Vero cells, whereas only type 2 became further
      attenuated after passage in secondary monkey kidney cells. After passage in Vero
      cells, type 3 poliomyelitis virus became more heat stable, as measured by its
      replicative capacity at 40 degrees C.

PMID- 7731029
TI  - Prevalence of IgE antibody to crude and purified allergens of Japanese cedar
      pollen among different troops of Japanese monkeys (Macaca fuscata).
AB  - We measured specific IgE antibodies to the crude allergen as well as two purified
      allergens (Cry j I and Cry j II) of Japanese cedar (Cryptomeria japonica--CJ)
      pollen in the serum of 276 Japanese monkeys in nine troops. Of 45 monkeys with CJ
      specific IgE in eight of nine troops, 23 (51%) were found to have IgE to both Cry
      j I and Cry j II, 21 (47%) only to Cry j I, and one (2.2%) only to Cry j II. The
      positive rate of specific IgE antibody to each allergen varied among the troops.

PMID- 7731030
TI  - Intrarectal inoculation of macaques by the simian immunodeficiency virus, SIVmne
      E11S: CD4+ depletion and AIDS.
AB  - Macaca nemestrina and Macaca fascicularis were inoculated with various doses of a
      single-cell clone of SIVmne-infected HuT 78 cells (E11S) by both the intravenous
      and intrarectal routes. Animals inoculated intravenously at each dose
      seroconverted and virus was isolated from peripheral blood mononuclear cells, but
      only the high-dose intrarectally exposed macaques became viremic and
      seroconverted. However, some seronegative, virus isolation negative intrarectally
      inoculated macaques showed evidence of infection and disease.

PMID- 7731031
TI  - A heterogeneous electrophysiological profile of bone marrow-derived mast cells.
AB  - Electrophysiological properties of mouse bone marrow-derived mast cells (BMMC)
      were studied under the whole-cell clamp configuration. About one third of the
      cells were quiescent, but others expressed either inward or outward currents.
      Inwardly rectifying (IR) currents were predominant in 14% of the cells, and
      outwardly rectifying (OR) currents in 24%. The rest (22%) of the cells exhibited
      both inward and outward currents. The IR currents were eliminated by 1 mM Ba2+,
      and were partially inhibited by 100 microM quinidine. The reversal potential was
      dependent on extracellular K+, thereby indicating that K+ mediated the IR
      currents. The negative conductance region was seen at potentials positive to EK.
      The OR currents did not apparently depend on the extracellular K+ concentration,
      but were reduced by lowering the extracellular Cl- concentration. The OR currents
      were partially blocked by 1 mM Ba2+, and were further blocked by a Cl- channel
      blocker, 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS). In addition, the
      reversal potential of the OR currents was positively shifted by decreasing the
      ratio of external and internal Cl- concentrations, suggesting that Cl- was a
      major ion carrier. In cells exhibiting IR currents, the membrane potential varied
      among cells and tended to depolarize by elevating the external K+ concentration.
      In cells with OR currents, the resting potential was hyperpolarized in
      association with an increase in conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731032
TI  - Differential regulation of membrane potential and conductance via intra- and
      extracellular pH in fused proximal tubular cells of frog kidney.
AB  - Intracellular pH (pHi), membrane potential (Vm) and membrane conductance (Gm) in
      fused proximal tubular cells of the frog kidney, were determined at three
      extracellular pH (pHo) values, 7.5, 8.5 and 6.5. Imposed changes of pHo by +/- 1
      pH unit induced parallel but smaller shifts of pHi. The alkaline milieu
      hyperpolarized the cells and increased Gm, whereas the acid milieu depolarized
      and lowered Gm. We subsequently introduced a weak acid and its conjugate base
      (acetic acid/acetate), or a weak base and its conjugate acid (NH3/NH4+), at pHo
      7.5, 8.5 and 6.5 to shift pHi without altering pHo, or to shift pHi against
      imposed changes of pHo. From these experiments, we observed that under some
      circumstances Vm varied with pHo but without Gm or pHi changes, whereas under
      other circumstances changes of Gm occurred during alterations of pHi while pHo
      and Vm remained unaltered. At pHi approximately 6.5 associated with Vm
      approximately -10 mV, Gm dramatically increased to quasi-infinite values. This
      increase was not an artifact since Gm returned to its control value following
      recovery to the control solution or in the presence of hyperosmotic solution. In
      conclusion, we demonstrate a differential regulation whereby Vm and Gm are
      controlled by pHo and pHi: pHo modulates mainly Vm and pHi modulates chiefly Gm.
      Furthermore, at pHi approximately 6.5 and Vm approximately -10 mV, our data
      reveal a large Gm that tends towards infinite values in a reversible fashion.

PMID- 7731033
TI  - Differential effect of triiodothyronine and thyroxine on the liposomal membrane
      in liquid-crystalline and gel state.
AB  - The effect of thyroid hormones on the degree of order or fluidity of dimyristoyl,
      dipalmitoyl or egg yolk phosphatidyl choline liposomes was evaluated by
      fluorescence spectroscopy methods. The freedom of molecular motion above the
      phase transition temperature was decreased, while below the transition, the
      mobility was actually increased by the incorporation of triiodothyronine to
      liposomes. While thyroxine decreases the fluidity in the liquid crystalline
      state, it cannot increase the fluidity in the gel state. A differential effect of
      triiodothyronine and thyroxine on the release of the liposomal content was found,
      depending on the liquid crystalline or gel state of the liposomes. These facts
      were correlated with the differential incorporation of the hormones to liposomes
      above and below the phase transition temperature of dimyristoyl and dipalmitoyl
      phospholipid choline. In gel state, a low incorporation of thyroxine compared
      with triiodothyronine was found.

PMID- 7731034
TI  - Voltage-dependent sodium channels in human small-cell lung cancer cells: role in
      action potentials and inhibition by Lambert-Eaton syndrome IgG.
AB  - Sodium channels of human small-cell lung cancer (SCLC) cells were examined with
      whole-cell and single-channel patch clamp methods. In the tumor cells from SCLC
      cell line NCI-H146, the majority of the voltage-gated Na+ channels are only
      weakly tetrodotoxin (TTX)-sensitive (Kd = 215 nM). With the membrane potential
      maintained at -60 to -80 mV, these cells produced all-or-nothing action
      potentials in response to depolarizing current injection (> 20 pA). Similar all
      or-nothing spikes were also observed with anodal break excitation. Removal of
      external Ca2+ did not affect the action potential production, whereas 5 microM
      TTX or substitution of Na+ with choline abolished it. Action potentials elicited
      in the Ca(2+)-free condition were reversibly blocked by 4 mM MnCl2 due to the
      Mn(2+)-induced inhibition of voltage-dependent sodium currents (INa). Therefore,
      Na+ channels, not Ca2+ channels, underlie the excitability of SCLC cells. Whole
      cell INa was maximal with step-depolarizing stimulations to 0 mV, and reversed at
      +45.2 mV, in accord with the predicted Nernst equilibrium potential for a Na(+)
      selective channel. INa evoked by depolarizing test potentials (-60 to +40 mV)
      exhibited a transient time course and activation/inactivation kinetics typical of
      neuronal excitable membranes; the plot of the Hodgkin-Huxley parameters, m
      infinity and h infinity, also revealed biophysical similarity between SCLC and
      neuronal Na+ channels. The single channel current amplitude, as measured with the
      inside-out patch configuration, was 1.0 pA at -20 mV with a slope conductance of
      12.1 pS. The autoantibodies implicated in the Lambert-Eaton myasthenic syndrome
      (LES), which are known to inhibit ICa and INa in bovine adrenal chromaffin cells,
      also significantly inhibited INa in SCLC cells. These results indicate that (i)
      action potentials in human SCLC cells result from the regenerative increase in
      voltage-gated Na+ channel conductance; (ii) fundamental characteristics of SCLC
      Na+ channels are the same as the classical sodium channels found in a variety of
      excitable cells; and (iii) in some LES patients, SCLC Na+ channels are an
      additional target of the pathological IgG present in the patients' sera.

PMID- 7731036
TI  - Identification of protein coding regions in genomic DNA.
AB  - We have developed a computer program, GeneParser, which identifies and determines
      the fine structure of protein genes in genomic DNA sequences. The program scores
      all subintervals in a sequence for content statistics indicative of introns and
      exons, and for sites that identify their boundaries. This information is weighted
      by a neural network to approximate the log-likelihood that each subinterval
      exactly represents an intron or exon (first, internal or last). A dynamic
      programming algorithm is then applied to this data to find the combination of
      introns and exons that maximizes the likelihood function. Using this method, we
      can rapidly generate ranked suboptimal solutions, each of which is the optimum
      solution containing a given intron-exon junction. We have tested the system on a
      large collection of human genes. On sequences not used in training, we achieved a
      correlation coefficient for exon nucleotide prediction of 0.89. For a subset of G
      + C-rich genes, a correlation coefficient of 0.94 was achieved. We have also
      quantified the robustness of the method to substitution and frame-shift errors
      and show how the system can be optimized for performance on sequences with known
      levels of sequencing errors.

PMID- 7731037
TI  - Solution structure of omega-conotoxin MVIIC, a high affinity ligand of P-type
      calcium channels, using 1H NMR spectroscopy and complete relaxation matrix
      analysis.
AB  - We have determined the solution structure of the omega-conotoxin MVIIC from Conus
      magus by 1H NMR. This conopeptide preferentially blocks P and Q type Ca2+
      currents by binding with high affinity to voltage-sensitive Ca2+ channels in
      neurons. This 26 residue peptide with three disulfide bonds was chemically
      synthesized and refolded for NMR structural studies. The 1H NMR NOESY spectrum of
      this peptide was completely assigned, with stereospecific assignments made for 12
      of the beta prochiral centers. Complete relaxation matrix analysis using
      MARDIGRAS was used to obtain initial interproton distances from peak intensities.
      The correlation time necessary for these calculations was determined by measuring
      13C relaxation times using inversely detected natural abundance spectra.
      Distances were input to DG, which provided 15 starting structures which were then
      subjected to restrained molecular dynamics calculations using SANDER with the
      AMBER 91 force field in vacuo. 1H-1H vicinal coupling constants were obtained
      using a combination of line fitting of both E. COSY and NOESY spectra and used to
      generate angle restraints that were included explicitly in the restrained
      molecular dynamics calculations. The final set of the 15 best structures had a
      backbone rmsd of 0.84 A. The ensemble R1/6 factor calculated by CORMA for the
      final 15 structures was 11%. The final structure consists of an anti-parallel,
      triple-stranded beta-sheet, with four turns. In spite of significant differences
      in amino acid sequence and affinities for calcium channel subtypes, the backbone
      structure of omega-conotoxin MVIIC is very similar to the previously reported
      structure of omega-conotoxin GVIA.

PMID- 7731038
TI  - Conservation of salt bridges in protein families.
AB  - A detailed computational analysis is presented that focuses on the relationship
      between structural attributes and the degree and mode of salt bridge
      conservation. A data set of conserved and non-conserved salt bridges was
      constructed from eight protein families, based on the structural alignment of
      family members. Salt bridges were defined at the secondary structure level rather
      than at the residue level, implying different possible modes of conservation:
      preservation (same charges at the same residue positions), compensation (reversal
      of charges), and complementation (maintenance of a salt bridge between two
      segments of secondary structures, not involving the same residue positions).
      Structural attributes such as the surface accessibility, distance from the active
      site, or type of secondary structures involved, were studied. No significant
      differences were found between conserved and non-conserved salt bridges, except
      for the surface accessibility. Conserved salt bridges were shown to be less
      exposed than non-conserved ones. Moreover, within the set of conserved salt
      bridges, the degree of conservation was shown to negatively correlate with
      surface exposure; however, not to an extent that could indicate a general role
      for electrostatic interactions in the protein interior. Examination of the most
      conserved salt bridge in each family showed a variety of typical features: Some
      involved the terminal segments of the protein, some were buried and one involved
      the catalytic site of the protein. Hence, the role of salt bridges is more
      specific, probably in fine tuning of a specific structure through the folding
      process or in determining the functional site. As for the conservation mode,
      preservations were found to predominate in the conserved interactions, while
      complementations were of secondary importance. Compensations occurred only rarely
      and mostly in exposed salt bridges, suggesting that this mechanism is not
      utilized frequently and especially not in important interactions.

PMID- 7731035
TI  - The biology of the P-glycoproteins.

PMID- 7731039
TI  - Structure and oxygen affinity of crystalline desArg141 alpha human hemoglobin A
      in the T state.
AB  - The correlation of a protein structure determined crystallographically to its
      functional properties determined in solution can be an extremely complex problem
      due to potential differences of protein conformational flexibility in the two
      physical states. A more direct approach to the correlation of structure with
      function is to examine both the structure and the function of a protein in the
      same crystalline environment. In this paper, the structural and functional
      properties of T state desArg hemoglobin (human hemoglobin modified by removal of
      the alpha-chain COOH-terminal residue, Arg141 alpha) have been studied in the
      same crystal form by high resolution X-ray diffraction methods and by polarized
      absorption microspectrophotometry. Specifically, the crystal structure of
      deoxygenated desArg human hemoglobin has been refined at a 2.1 A resolution using
      crystals grown at low salt concentration from solutions of polyethylene glycol.
      The loss of Arg141 alpha and all of the salt bridges in which it participates is
      associated with subtle structural perturbations of the alpha-chains which include
      an increase in the conformational flexibility of both the NH2 and COOH-terminal
      peptides. Although the heme pockets appear unchanged and even the side-chain of
      Tyr140 is oriented nearly as in HbA, the functional characterization by
      microspectrophotometric measurements indicates that crystals of desArg hemoglobin
      bind oxygen with an affinity which is roughly 15-fold greater than that of
      crystals of human hemoglobin A. There is no alkaline Bohr effect or effect of
      chloride ions, but an acid Bohr effect is observed. The oxygen affinities
      measured along two principal axes of the crystals differ by 25%, indicating
      heterogeneity in the affinities of the oxygen binding sites. This finding and the
      measured Hill coefficient of unity suggest significant cooperativity in the
      binding of oxygen in these crystals. The origins of the observed heterogeneity
      and the implied cooperativity are unknown.

PMID- 7731040
TI  - A study of four-helix bundles: investigating protein folding via similar
      architectural motifs in protein cores and in subunit interfaces.
AB  - Four-helix bundles are identified and characterized in the subunit interfaces of
      protein multimers. We find that this motif occurs as often in the interfaces as
      in the protein monomers. Common and different characteristics demonstrated by the
      bundles in the two environments suggest the possible stabilization mechanisms of
      the bundles via cooperative helical twist, dipole alignment and interhelical
      connections. Nucleation of parallel helix pairs may be a favourable pathway
      before the pairs couple into bundles during folding. Certain properties found
      chaotic in the interface four-helix bundles indicate that either the subunit
      association is far from the global minimum conformation, or that the footprints
      of the folding pathway are recorded in these properties.

PMID- 7731041
TI  - Solution structure of the covalent duocarmycin A-DNA duplex complex.
AB  - Duocarmycin A is an antitumour antibiotic that binds covalently to the minor
      groove N-3 position of adenine with sequence specificity for the 3'-adenine in a
      d(A-A-A-A) tract in duplex DNA. The adenine ring becomes protonated on
      duocarmycin adduct formation resulting in charge delocalization over the purine
      ring system. We report on the solution structure of duocarmycin A bound site
      specifically to A12 (designated *A12+) in the sequence context d(T3-T4-T5
      T6).d(A9-A10-A11-*A12+) within a hairpin duplex. The solution structure was
      solved based on a combined NMR-molecular dynamics study including NOE based
      intensity refinement. The A and B-rings of duocarmycin are positioned deep within
      the walls of the minor groove with the B-ring (which is furthest from the
      covalent linkage site) directed towards the 5'-end of the modified strand.
      Duocarmycin adopts an extended conformation and is aligned at approximately 45
      degrees to the helix axis with its non-polar concave edges interacting with the
      floor of the minor groove while its polar edges are sandwiched within the walls
      of the minor groove. The T3.*A12+ modification site pair forms a weak central
      Watson-Crick hydrogen bond in contrast to all A.T and G.C pairs, which align
      through standard Watson-Crick pairing in the complex. The helical parameters are
      consistent with a minimally perturbed right-handed duplex in the complex with
      minor groove width and x-displacement parameters indicative of a B-form helix. A
      striking feature of the complex is the positioning of duocarmycin A within the
      walls of the minor groove resulting in upfield shifts of the minor groove sugar
      protons, as well as backbone proton and phosphorus resonances in the DNA segment
      spanning the binding site.

PMID- 7731042
TI  - Model structure of the Omp alpha rod, a parallel four-stranded coiled coil from
      the hyperthermophilic eubacterium Thermotoga maritima.
AB  - Omp alpha is an outer-membrane protein that spans the periplasmic space of the
      hyperthermophilic eubacterium Thermotoga maritima. The molecule contains a
      globular head with an apparent diameter of 8 nm and a rod-shaped tail of 40 nm
      length. The sequence of the globular domain is homologous to a conserved region
      of cell wall-bound proteins and probably attaches Omp alpha to the peptidoglycan.
      The sequence of the rod domain resembles that of coiled coil proteins and ends in
      a transmembrane segment that anchors Omp alpha to the outer membrane. We have
      analysed Omp alpha by scanning transmission electron microscopy (STEM) and by
      statistical sequence analysis methods. The Omp alpha rod is a tetramer with an
      unusual periodicity of hydrophobic residues close to 3.6 that differs from the
      3.5 periodicity of canonical coiled coils. This is due to periodic omissions of
      three residues in the heptad repeat pattern ("stutters") whose effect is to
      locally distort the packing of hydrophobic layers in the core of the coiled coil.
      Residues in position alpha are shifted to occupy a position halfway between
      positions alpha and d (x layers) and residues in positions d and e are shifted so
      that both participate in core packing interactions (da layers). Such distorted
      layers are frequently found in helical bundles and are characteristic of helices
      that do not undergo supercoiling. The only homo-oligomeric coiled coil of known
      structure which contains x and da layers is the three-stranded coiled coil of
      influenza haemagglutinin. Using geometric constraints derived from this
      structure, we have built a model for the Omp alpha rod in which the helices have
      a crossing angle of less than 15 degrees and maintain a residual degree of
      supercoiling with a pitch of approximately 40 nm. Our analysis of distorted
      layers in the hydrophobic core of coiled coils and helical bundles shows that
      stutters must not be viewed as discontinuities but rather as a departure from the
      canonical "knobs-into-holes" packing that allows helices to interact at a low
      angle without supercoiling. Although stutters have been considered to weaken
      helical interactions, their occurrence in a rigid, highly thermostable coiled
      coil indicates that this may not be generally true. Our analysis also indicates
      that skips and stutters are two different conventions for describing the same
      underlying structural feature.

PMID- 7731043
TI  - Footprint analysis of M.Sssl and M.Hhal methyltransferases reveals extensive
      interactions with the substrate DNA backbone.
AB  - The interactions of the CpG methyltransferases M.Sssl and M.Hhal (GCGC) with
      substrate DNA were investigated using three different footprinting techniques.
      The two structurally related enzymes displayed similar specific and non-specific
      contacts with DNA while bound to their target sequences. DNase I footprinting
      implicated a region of 18 to 21 base-pairs with which these enzymes interact.
      Dimethylsulfate protection experiments mostly revealed specific base
      interactions; each enzyme was shown to interact predominantly with bases at its
      recognition site in the major groove. However, hydroxyl radical footprints
      demonstrated extensive interactions with the sugar-phosphate backbone on both
      strands of the DNA substrate. Both enzymes protected a 16 nucleotide region, in a
      staggered fashion, covering 9 to 10 nucleotides on each strand. The protected
      regions, extending for almost a full turn of DNA on each strand, were offset by 6
      to 7 nucleotides in the 5' direction, placing both regions on the same face of
      the double helix, bracketing the major groove. The results suggest that these
      methyltransferases straddle the major groove from the backbone, but protrude into
      the groove only to specifically interact with their recognition sites. The
      sequence-independent interactions observed on the sugar-phosphate backbone may
      explain the ability of the enzymes to recognize a small sequence, as well as
      their processive mode of action.

PMID- 7731044
TI  - Association of antibody chains at different stages of folding: prolyl
      isomerization occurs after formation of quaternary structure.
AB  - The folding pathways of multi-domain proteins are still poorly understood due to
      the complexity of the reaction involving domain folding, association and, in many
      cases, prolyl cis/trans isomerization. Here, we have established a kinetic model
      for the folding of the Fab fragment of the antibody MAK 33 with intact disulfide
      bonds. Folding of the hetero-dimeric protein from the completely denatured,
      oxidized state comprises the pairwise association of the two domains of each
      chain with those of the partner protein. Both the reactivation of the Fab
      fragment in which the two constituent polypeptide chains were covalently linked
      via a cystine bond (Fab) and that of a mutant lacking this covalent linkage (Fab/
      cys) were monitored by ELISA. Folding of the Fab fragment is a slow process,
      which can be described by a single exponential term. The kinetic phase reflects a
      folding step after the association of the two chains. The same reaction was
      detected in the folding of Fab/-cys but an additional rate-limiting step is
      involved that is due to a unimolecular step in the folding of the isolated light
      chain. This implies that, during Fab reactivation, Fd associates with the light
      chain at the stage of an earlier folding intermediate, thus eliminating the
      additional slow folding step of the light chain observed with Fab/-cys. Both in
      Fab and Fab/-cys renaturation, the folding reaction after association is
      determined by prolyl isomerization. Therefore, at least four different
      association-competent folding intermediates have to be postulated according to
      the folding stage of light chain and the configuration of at least one prolyl
      peptide bond. Using the different substrate specificities of cyclophilin and
      FK506 binding protein, we have obtained evidence that Pro159 within the Fd
      fragment may be responsible for the observed slow folding phase after
      association, although three other proline residues adopt a cis configuration in
      the native protein. Furthermore, the data suggest that in the case of the Fab
      fragment, association is a prerequisite for cis/trans isomerization of prolyl
      peptide bonds, implying that the quaternary but not the tertiary structure
      determines the cis-configuration of the prolyl residue in Fd involved in the rate
      limiting folding reaction.

PMID- 7731045
TI  - Interaction of the RNA binding fingers of Xenopus transcription factor IIIA with
      specific regions of 5 S ribosomal RNA.
AB  - Zinc fingers 4 to 7 of Xenopus transcription factor IIIA (TFIIIA) represent the
      minimal polypeptide necessary for high-affinity binding to 5 S RNA. Mutations
      covering the entire 5 S RNA structure have been compared for their effects on the
      binding affinity of full-length TFIIIA and a polypeptide consisting of fingers 4
      to 7 of TFIIIA (zf4-7). In addition, ribonuclease footprinting was used to
      compare the binding sites of TFIIIA and zf4-7 on 5 S RNA. The consistency between
      the data obtained from these two approaches provided a clear indication that zinc
      fingers 4 to 7 of TFIIIA bind to a central core region on the 5 S RNA molecule
      consisting of loop B/helix II/loop A/helix V/region E. This information was used
      to design a truncated 75-nucleotide-long RNA molecule that retains high affinity
      for zf4-7. Therefore, we conclude that the specific interaction of TFIIIA with 5
      S RNA can be represented by a complex formed between a four zinc finger
      polypeptide and a truncated 5 S RNA molecule.

PMID- 7731046
TI  - Evolution of the phycobiliproteins.
AB  - Amino acid sequence alignments and phylogenetic analyses have been used to
      examine the relationships among 100 phycobiliprotein sequences. The alignments
      revealed a number of highly conserved amino acid residues that are involved in
      chromophore attachment and conformation, alpha-beta interactions and
      phycobilisome assembly. The phylogenetic analysis confirmed that the
      phycobiliprotein subfamilies, previously classified by their biochemical and
      spectroscopic properties, also formed coherent evolutionary groups. The alpha and
      beta subunits formed two distinct evolutionary lines that originate from a common
      ancestor. The pattern of divergence among the alpha subfamilies was identical to
      that of the beta subfamilies, strongly suggesting that the alpha and beta
      subunits of each phycobiliprotein type have coevolved. The phylogenetic data
      support a monophyletic separation of the eukaryotic sequences from the extant
      cyanobacterial sequences. The eukaryotic phycoerythrins appeared more closely
      related to the marine Synechococcus phycoerythrins than to the other
      cyanobacterial phycoerythrins. The cryptophyte phycobiliproteins formed a
      monophyletic group within the rhodophyte lineage. In conjunction with other
      phylogenetic markers, the analysis of additional phycobiliprotein sequences may
      help to further resolve the relationships among phycobiliprotein-containing
      organisms.

PMID- 7731047
TI  - Selection and application of human single chain Fv antibody fragments from a semi
      synthetic phage antibody display library with designed CDR3 regions.
AB  - We have constructed a large (3.6 x 10(8) clones) phage display library of human
      single chain Fv (scFv) antibody fragments by combining 49 germline VH genes with
      synthetic heavy chain CDR3 (HCDR3) regions and seven light chains. The HCDR3
      regions varied in length between 6 and 15 residues and were designed to contain
      fully randomized stretches of amino acid residues flanked by regions of limited
      residue variability that were composed of amino acid residues that frequently
      occur in natural antibodies. We reasoned that this approach would increase the
      frequency of functional molecules in our library and, in addition, permit us to
      efficiently utilize available cloning space. By direct selection on solid phase
      bound antigens we obtained phage antibodies with binding activities to 13
      different antigens, including Von Willebrand factor, the DNA-binding HMG box of
      transcription factor TCF-1 and the tumor antigen EGP-2. In addition, we applied a
      competitive selection procedure to target phage antibodies to the desired portion
      of a recombinant fusion protein and to select phage antibodies capable of
      discriminating between the two highly homologous homeobox proteins PBX1a and
      PBX2. The functional capacity of monoclonal phage antibodies was assessed in
      immuno-histochemical staining of tissue specimens. Western blotting assays and
      immunofluorescent analysis of cells by flow cytometry. The results demonstrate
      that this large human phage antibody library contains a broad assortment of
      binding specificities that can be applied in a variety of biochemical assays.

PMID- 7731048
TI  - The relationship between phosphorylation potential and redox state in the
      isolated working rabbit heart.
AB  - The effects of the cytosolic and mitochondrial redox state on the function and
      phosphorylation potential of working perfused rabbit hearts were studied. Hearts
      were perfused with glucose, while lactate, aminooxy-acetate (an inhibitor of the
      malate-aspartate shuttle), beta-hydroxybutyrate, and pyruvate were sequentially
      added to the perfusate to manipulate the cytosolic and mitochondrial NAD+/NADH
      ratio. The phosphorylation potential and product of ADP and P(i) were both found
      to be proportional to mitochondrial redox state. There was no overall
      relationship between cytosolic redox potential and the ATP/ADP x P(i) ratio,
      although at high mitochondrial NADH, there was a tendency for the states with
      more reduced cytoplasm to be associated with a lower phosphorylation potential.
      Cardiac output and dP/dt were decreased after 75 microM aminooxy-acetate was
      present for 15 min, and remained low when 0.5-1.0 mM beta-hydroxybutyrate was
      added, even though the beta-hydroxybutyrate period was characterized by both very
      low cytosolic NAD+/NADH and high mitochondrial NADH. Function returned to normal
      when the cytoplasm was oxidized by addition of 10 mM pyruvate, and although MVO2
      rose from 4.0 +/- 0.4 to 5.0 +/- 0.5, this was not accompanied by statistical
      changes in either mitochondrial NADH or phosphorylation potential. Therefore, the
      cytosolic redox state may play a role in cardiac function, but has only a minor
      contribution to the regulation of the phosphorylation potential in the working
      perfused rabbit heart.

PMID- 7731049
TI  - Postnatal changes in the G-proteins, cyclic nucleotides and adenylyl cyclase
      activity in rabbit heart cells.
AB  - We have studied the postnatal changes in the levels of isoforms of stimulatory
      (Gs) and inhibitory (Gi) G-proteins, cAMP and cGMP in washed particulate
      membranes (WPM) from whole ventricles as well as from isolated ventricular
      myocytes and have also measured adenylyl cyclase (AC) activity in WPM prepared
      from isolated myocytes of adult (AD) and newborn (NB) rabbit heart. Immunoblot
      analysis for the levels of Gi alpha 1, G alpha 2, Gi alpha 3 and Gs alpha
      subunits showed that Gi alpha 2 and Gi alpha 3 were higher in WPM from whole
      ventricles of NB compared to AD. This ratio was much higher in WPM from isolated
      ventricular myocytes since Gi alpha 2 and Gi alpha 3 were either absent or
      present in extremely low immunodetectable levels in WPM from AD ventricular
      myocytes. Gi alpha 1 levels were not different for AD compared to NB WPM, whether
      prepared from whole ventricle or from isolated myocytes. Two forms of Gs alpha, a
      small form (Gs alpha-S) and a large form (Gs alpha-L), were immunodetected at 43
      and 48 kDa, respectively. The Gs alpha-S form was higher in AD WPM and the Gs
      alpha-L form was higher in NB WPM while the total Gs alpha(L+S) was not
      different. The Gs alpha results for WPM from isolated myocytes were not different
      from the results for WPM from whole ventricles. Basal levels of cAMP were 80%
      higher in NB compared to AD whole ventricles and were 200% higher in NB compared
      to AD isolated myocytes. Levels of cGMP were 4-5 fold higher in NB than in AD
      myocytes and ventricular tissue. Basal AC activity was higher in NB than in AD
      WPM from isolated myocytes and was enhanced by Gpp(NH)p pretreatment in AD but
      not in NB WPM. The isoproterenol-induced increase in AC activity was higher in AD
      compared to NB WPM and was completely abolished by Gpp(NH)p pretreatment in NB
      but not in AD WPM. Forskolin caused a greater increase in AC activity in NB than
      in AD WPM. The post-natal decrease in the levels of Gi alpha 2 and Gi alpha 3,
      particularly in isolated ventricular myocytes, may help to explain the smaller
      effects of isoproterenol and greater muscarinic influence on ICa, as we
      previously showed, and the smaller effect of isoproterenol on AC activity in NB
      compared to AD WPM.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7731050
TI  - Calcium overload during reperfusion is accelerated in isolated hypertrophied rat
      hearts.
AB  - In this study, calcium overload during reperfusion and the severity of
      morphologically evident ischemic myocardial injury were compared in hypertrophied
      and normal hearts. Hypertrophied hearts isolated from rats where a clip had been
      placed on the proximal thoracic aorta for 6 weeks were compared to those from
      sham-operated rats in an isolated state perfused with Krebs-Henseleit buffer
      containing 3% albumin, 1.2 mM palmitate and 11 mM glucose. The isolated hearts
      were exposed to global, no-flow, normothermic ischemia following potassium arrest
      and were reperfused. Following ischemia and reperfusion, left ventricular end
      diastolic pressure was increased (39 +/- 7 v 13 +/- 2 mmHg, P < 0.05), and
      percentage recovery of left ventricular systolic function was decreased (34.4 +/-
      8.9 v 77.1 +/- 6.3% P < 0.05), in hypertrophied hearts compared to control
      hearts. Calcium overload during reperfusion was two and one-half times greater in
      the hypertrophied hearts than in the control hearts and showed significant
      relationships with recovery of left ventricular systolic function (r = -0.86, P <
      0.001) and left ventricular end diastolic pressure (r = 0.78, P < 0.005).
      Myocardial energy charge did not differ between the two groups at the end of
      reperfusion. Ischemic myocardial injury was quantitated morphologically by point
      counting techniques in a comparable series of control and hypertrophied hearts.
      After ischemia, hearts were either exposed to a monoclonal antimyosin antibody to
      identify and measure irreversibly injured myocardium by light microscopy or fixed
      by perfusion with 2.5% glutaraldehyde to quantitate the morphologic changes
      ultrastructurally. Control and hypertrophied hearts were not significantly
      different in severity of myocardial injury due to ischemia as assessed
      morphologically. Thus, the data suggest that calcium overload during reperfusion
      plays a significant role in post-ischemic left ventricular dysfunction of the
      hypertrophied heart. The accelerated calcium overload that occurs in the
      hypertrophied rat heart during reperfusion cannot be explained by differences in
      severity of myocardial injury during ischemia which indicates that other
      mechanisms are responsible.

PMID- 7731051
TI  - Expression of regulated cardiac troponin I in Escherichia coli.
AB  - The study of the functional effects of troponin isoform changes would be greatly
      aided by the development of a strategy permitting protein engineering and
      mutational analysis. To assess the role of troponin isoforms in regulating
      myofibrillar ATPase activity, we have expressed rat cardiac troponin I (cTnI) in
      E. coli and purified the protein to near homogeneity. We utilized the inducible
      expression vector pGEX-KG to create a glutathione-S-transferase fusion protein
      which can be cleaved with thrombin. Approximately 6 mg of cTnI can be purified
      from 1 l of culture. Ca2+Mg2+ ATPase activity was measured using the bacterially
      synthesized cTnI and the remaining components of the regulated actomyosin complex
      (troponin T, troponin C, tropomyosin, actin, and myosin) purified to homogeneity
      from mammalian hearts. In the presence of free Ca2+ ranging from 10(-2) to 10(-8)
      M, bacterially synthesized cTnI exhibits specific activity similar to that
      observed for control cTnI isolated from rat hearts. The bacterially synthesized
      protein is capable of stoichiometric phosphorylation and demonstrates
      appropriately regulated specific activity. These results establish the
      feasibility of using bacterial expression to study functional consequences of
      changes in expression of troponin isoforms.

PMID- 7731052
TI  - Biochemical, mechanical and energetic characterization of right ventricular
      hypertrophy in the ferret heart.
AB  - Ferret right ventricular hypertrophy is characterized by a decreased and
      prolonged isometric contraction, associated with altered intracellular calcium
      (Ca2+) regulation. However myofibrillar composition, cross-bridge function and/or
      energy transfer may also be involved in these contractile disturbances.
      Therefore, mechanical properties of myofibrils have been studied with Triton X
      100-skinned fibres and troponin (Tn) T and I composition has been examined.
      Mitochondrial function and functional activity of creatine kinase (CK) isoforms
      have been studied in saponin-skinned fibres of control (C) and hypertrophied (H)
      ferret right ventricle, to check for a possible mismatch between energy
      production and utilization. Our results show that neither TnT nor TnI isoform
      expression, nor myofibrillar Ca2+ responsiveness (similar apparent Ca2+
      sensitivity and Hill coefficient) were affected by pressure-overload. Similarly,
      maximal tension and stiffness, as well as cross-bridge cycling rate (v)--assessed
      by quick length changes--were not significantly altered. Importantly, passive
      stiffness was dramatically increased (163 +/- 30 mN/mm2/microns for C v 500 +/-
      121 mN/mm2/microns for H; P < 0.02). Moreover, there was a significant
      correlation between passive stiffness and cross-bridge cycling rate, indicating
      that a factor involved in the passive stiffness may affect cross-bridge kinetics.
      Oxidative capacity (normalized to ventricular dry weight), reflecting
      mitochondrial ATP production and mitochondrial CK efficacy, as well as
      myofibrillar CK efficacy (assessed by the shift of MgATP-rigor tension curves
      before and after phosphocreatine addition), were similar in both groups. These
      results demonstrate that ferret right ventricular pressure-overload was
      accompanied by a development of myofibrils and a parallel increase of energy
      production capacity, transfer and utilization. Decreased compliance, probably
      linked to an increase in the collagen fraction and/or alterations of the
      cytoskeletal architecture of the overloaded ventricle, could contribute to the
      slower time course and decreased amplitude of the isometric twitch.

PMID- 7731053
TI  - Low particulate type IV phosphodiesterase activity in hypothyroid rat atria.
AB  - Rats were made hypothyroid by adding propylthiouracil (PTU) to their drinking
      water. Some of the PTU-treated rats were given thyroid hormone injections for 5
      days. Both soluble and particulate cAMP-phosphodiesterase activities of adipose
      and ventricular tissues were increased by 25-60% in hypothyroidism. In left
      atria, soluble cAMP-phosphodiesterase activity was not significantly altered in
      hypothyroidism, while total particulate cAMP-phosphodiesterase activity was
      lowered by 30%. This lowering was due to diminished isoenzyme IV activity, as
      studied with the isoenzyme-specific inhibitors rolipram and SK&F 94836. In
      conclusion, the present results show decreased particulate type IV cAMP
      phosphodiesterase activity in hypothyroid rat atria. This may explain the
      increased responsiveness to isoproterenol in hypothyroid atria.

PMID- 7731054
TI  - Modulation of calcium uptake in cultured cardiac muscle cells by 1,25
      dihydroxyvitamin D3.
AB  - Recent studies have provided evidence indicating that 1,25-Dihydroxyvitamin D3
      [1,25(OH)2D3] rapidly stimulates calcium influx through Ca2+ channels in isolated
      chick heart tissue and cells. Studies were performed both to evaluate the
      characteristics of the hormone action in cultured myocytes and to obtain
      information on the metabolic pathway which mediates its effects. Treatment of 70
      80% confluent chick embryo myocyte monolayers with 1,25(OH)2D3 induced a fast
      (within 3-5 min) stimulation of 45Ca uptake which was dose-dependent, maximum
      responses (130% above controls) being elicited at a concentration of 10(-10) M.
      Physiological levels of 25(OH)D3 and 24,25(OH)2D3, and the synthetic analog 1
      alpha (OH)D3, had lower activity. Coincident with the rapid changes in Ca uptake,
      1,25(OH)2D3 significantly increased cAMP levels. The hormone-induced increase in
      cAMP was not blocked by nifedipine. Compound SQ 22536, a specific inhibitor of
      adenylate cyclase, completely suppressed the effects of the sterol on cAMP and Ca
      uptake. Furthermore, GDP-beta-S inhibited the increase in Ca uptake by
      1,25(OH)2D3. These results involve the adenylate cyclase pathway and the
      participation of G proteins in 1,25(OH)2D3 stimulation of Ca influx in chick
      heart cells.

PMID- 7731055
TI  - Effects of regional myocardial lidocaine infusion on high energy phosphates.
AB  - High energy phosphates [phosphocreatine (PCr) and adenosine triphosphate (ATP)]
      are maintained in the heart under conditions of altered myocardial contractility
      and under certain conditions of maintained in the heart under conditions of
      altered myocardial contractility and under certain conditions of myocardial
      ischemia (such as hibernating myocardium). However, the metabolic consequences of
      reduced regional contractility have not been investigated. This study was
      designed to test the hypotheses that (1) under conditions of normal blood flow,
      reduction in regional contractility does not result in changes in PCr or ATP and
      (2) under conditions of reduced blood flow, reduction in regional contractility
      prevents the expected decline in high energy phosphates usually seen in regional
      ischemia. An in situ open chest swine preparation was used in which regional
      contractility was reduced with the administration of intracoronary lidocaine.
      High energy phosphates were measured using phosphorus-31 magnetic resonance
      spectroscopy (NMR) under conditions of normal flow and reduced flow.
      Intracoronary lidocaine infusion in 9 animals did not change blood flow from
      basal levels, but significantly reduced regional segment shortening from 0.16 +/-
      0.02 to 0.02 +/- 0.01. The ratio of PCr/ATP did not change with lidocaine
      infusion (control: 1.53 +/- 0.09; lidocaine: 1.59 +/- 0.11), but oxygen content
      in the anterior interventricular vein increased from 8.25 +/- 0.69 to 9.83 +/-
      0.91 ml/O2/100 ml blood in parallel studies (P = 0.04). While the lidocaine
      infusion was maintained, subsequent coronary stenosis significantly reduced
      subendocardial blood flow from 0.91 +/- 0.06 to 0.41 +/- 0.06 ml/min/g without
      significantly altering high energy phosphates (PCr/ATP = 1.51 +/- 0.15). In
      contrast to the 29% decline in PCr previously seen with regional ischemia, PCr
      was unchanged with this degree of flow reduction in the presence of lidocaine.
      Thus, PCr and ATP are unchanged under conditions of reduced contractility,
      consistent with equilibrium of energy synthesis and utilization. In addition,
      factors which reduce myocardial contractility, either pharmacologically or
      endogenously, protect against the metabolic consequences of reduced flow by
      reducing MVO2.

PMID- 7731056
TI  - Adenosine formation during hypoxia in isolated hearts: effect of adrenergic
      blockade.
AB  - Adrenergic receptor blockade has been reported to decrease cardiac adenosine
      formation and release during hypoxia. We wished to determine whether this occurs
      by an improvement in the energy supply/demand ratio. Isolated guinea pig hearts
      were perfused at a constant pressure of 50 mm Hg. Hypoxia (30% O2) was maintained
      for 20 min while adenosine release and venous PO2 were measured in the coronary
      venous effluent. beta-adrenergic blockade with 5 microM atenolol did not change
      hypoxic adenosine release (Control: 15.6 +/- 2.7, Atenolol: 23.6 +/- 5.7
      nmol/g/20 min). Addition of 6 microM phentolamine with atenolol significantly
      reduced hypoxic adenosine release (4.4 +/- 1.4 nmol/g/20 min, P < 0.05). Atenolol
      was without hemodynamic effects, but addition of phentolamine reduced left
      ventricular pressure development, heart rate, and oxygen consumption prior to
      hypoxia. Atenolol plus phentolamine did not change venous PO2 during hypoxia.
      Treatment with phenoxybenzamine (1 microM) plus atenolol also reduced adenosine
      release (7.4 +/- 0.8 nmol/g/20 min). Control experiments and atenolol plus
      phentolamine experiments were repeated using 31P-NMR to measure high energy
      phosphates. Adrenergic blockade had no effect on phosphate concentrations during
      normoxia, but resulted in higher [PCr], lower [P(i)] and higher phosphorylation
      potentials during hypoxia. Adrenergic blockade also prevented the hypoxia-induced
      rise in intracellular [H+], [AMP] and [ADP] seen in control hearts. The changes
      in phosphorylation potential are correlated with similar changes in adenosine
      release in adrenergically intact hearts. We conclude that the primary effect of
      adrenergic blockade during hypoxia is a reduction in ATP use due to alpha
      receptor blockade. This leads to improved high energy phosphate concentrations
      during hypoxia and a reduction in adenosine formation.

PMID- 7731057
TI  - Role of EDRF in the regulation of shear rate in large coronary arteries in
      conscious dogs.
AB  - To determine whether dilation of large coronary arteries normalizes shear during
      increased flow following brief occlusion, six dogs were instrumented to measure
      aortic and left ventricular pressures, left circumflex coronary artery external
      diameter, and coronary blood flow. The coronary artery was occluded for 15 or 30
      s. Data were obtained before and after blockade of EDRF synthesis with nitro-L
      arginine. Internal coronary artery diameter and wall shear were calculated on a
      moment-to-moment basis and the area under the flow curve was measured. Peak flow
      and shear rate were unaffected by NLA or by the occlusion duration. Flow curve
      area increased with the duration of occlusion. Internal and external diameters
      increased significantly for 15 s occlusions before NLA (by 4 +/- 1% in external
      diameter and by 11 +/- 4% in internal diameter) and for 30 s occlusions before
      NLA (by 5 +/- 1% in external diameter and by 14 +/- 5% in internal diameter) but
      not after NLA. Adenosine infusions of 0.05, 0.10, 0.50, and 1.0 mumol/kg/min were
      also used to dilate the coronary arteries. With each infusion, flow, shear and
      diameter were allowed to reach steady state. Steady state shear was reduced only
      slightly and did not approach the baseline state. We conclude that increased
      shear rate causes an increase in coronary artery diameter which is EDRF
      dependent. Increased coronary artery diameter during reactive hyperemia and
      adenosine infusions did not normalize wall shear.

PMID- 7731058
TI  - Fatty acid transfer across the myocardial capillary wall: no evidence of a
      substantial role for cytoplasmic fatty acid-binding protein.
AB  - It has recently been hypothesized that fatty acid (FA) transfer across the
      myocardial capillary wall is mediated by cytoplasmic fatty acid-binding protein
      (FABP). Therefore, we studied the type and content of FABP in endothelial cells
      from rat heart, using molecular biological, immunochemical, and FA-binding
      assays. Studies were performed on short term cultured endothelial cells, two
      established endothelial cell lines and ultrathin cryosections from adult rat
      heart. Northern blotting analysis of endothelial cell RNA failed to detect either
      heart-type (H-) FABP or liver-type (L-) FABP mRNA, but the reversed transcription
      polymerase chain reaction revealed both H- and L-FABP mRNAs, indicating the
      presence of minor amounts of these mRNAs. Highly sensitive immunochemical assays
      (sandwich ELISAs) using specific antibodies raised against rat H- or L-FABP
      showed the contents of these FABP-types in endothelial cells to be 1-5 ng/mg
      cytosolic protein, which is more than three orders of magnitude lower than the
      contents of H-FABP in heart or L-FABP in liver. Immuno-electron microscopy also
      showed that the concentration of H-FABP in endothelial cells is at least two
      orders of magnitude lower than that in cardiomyocytes. Finally, cytosolic protein
      samples from endothelial cells revealed no significant FA-binding activity in the
      15-kDa region. We conclude that rat heart endothelial cells contain only minor
      quantities of cytoplasmic FABP and that, therefore, FA transport over the
      endothelium is mediated by FABP only to a minor extent. It is postulated that
      aqueous diffusion of FA through the endothelial cytoplasm most likely accounts
      for the experimentally observed rates of cardiac FA utilization.

PMID- 7731059
TI  - Effect of angiotensin II on calcium release phenomena in normal and hypertrophied
      single cardiac myocytes.
AB  - The effects of angiotensin II (Ang II) (10(-9) M to 10(-7) M) on calcium releases
      were established in ventricular myocytes from normal and renal hypertensive adult
      rats. From each peak systolic indo-1 ratio (405 nm/480 nm), amplitude variation,
      duration (rise time and fall time), and frequency of spontaneous calcium releases
      were investigated on freshly isolated cardiomyocytes at rest or under electrical
      stimulation. The following changes were observed: (1) in spontaneous contracting
      myocytes, an increase in frequency of calcium transients at 10(-7) M in normal
      cells (+157%, P < 0.05) and at whatever angiotensin II concentration in
      hypertrophied cells (10(-9) M: +79% P < 0.05; 10(-8) M +82%, P < 0.01; 10(-7) M:
      +285%, P < 0.01) with a greater sensitivity of hypertrophied cells to Ang II (P <
      0.05 at 10(-9) M, P < 0.01 at 10(-8) M). (2) In stimulated myocytes, a
      prolongation of the duration of calcium transients at 10(-7) M in normal cells
      (+68%, P < 0.01) and at 10(-9) M, 10(-8) M, 10(-7) M in hypertrophied cells:
      (+36%, P < 0.05; +39%, P < 0.01; +77%, P < 0.01) with a greater sensitivity of
      hypertrophied myocytes (P < 0.05 at 10(-9) M and 10(-8) M). An increase in
      duration may be explained by the occurrence of calcium releases during the fall
      time of calcium transients. Thus, both in normal and hypertrophied myocytes, Ang
      II induced the occurrence of calcium releases with increased sensitivity of
      hypertrophied cells to Ang II. Such calcium releases are known to be a possible
      cause of arrhythmias termed "triggered activity".

PMID- 7731060
TI  - Epitope mapping of the alpha-chain of the insulin-like growth factor I receptor
      using antipeptide antibodies.
AB  - Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth
      muscle cells (VSMC). The IGF I receptor (IGF IR) is a heterotetramer composed of
      two cross-linked extracellular alpha-chains and two membrane-spanning beta-chains
      that contain a tyrosine-kinase domain. It has a high degree of sequence
      similarity to the insulin receptor (IR), and the putative ligand-specific binding
      site has been localized to a cysteine-rich region (CRR) of the alpha-chain. To
      obtain insights into antigenic determinants of the IGF IR, we raised a panel of
      site-specific polyclonal antibodies against short peptide sequences N-terminal to
      and within the CRR. Several antibodies raised against linear epitopes within the
      CRR bound to solubilized and native rat and human IGF IR by ELISA, did not cross
      react with IR, but unexpectedly failed to inhibit 125I-IGF I binding. A
      polyclonal antibody directed against a 48-amino acid synthetic peptide,
      corresponding to a region of the CRR postulated to be essential for ligand
      binding, failed to react with either solubilized, reduced or intact IGF IR. Three
      antibodies specific for the N-terminus of the alpha-chain reacted with
      solubilized and native IGF IR. One of these, RAB 6, directed against amino acids
      38-44 of the IGF IR, inhibited 125I-IGF I binding to rat aortic smooth muscle
      cells (RASM) and to IGF IR/3T3 cells (overexpressing human IGF IR) by up to 45%.
      Immunohistochemical analysis revealed strong IGF IR staining in the medial smooth
      muscle cell layer of rat aorta. These findings are consistent with a model
      wherein conformational epitopes within the CRR and linear epitopes within the N
      terminus of the alpha-chain contribute to the IGF I binding pocket. These
      antibodies should provide a valuable tool to study structure-function
      relationships and in vivo regulation of the IGF IR.

PMID- 7731061
TI  - Effects of taurine and taurine analogues on the phosphorylation of a 44 kDa
      protein present in a mitochondrial subfraction of the rat heart: partial
      characterization of the 44 kDa phosphoprotein.
AB  - Recent studies suggest that taurine (2-aminoethanesulfonic acid) is involved in
      the regulation of protein phosphorylation in excitable tissues such as the
      retina, brain and heart. In order to determine the structural requirements for
      the effect of taurine on the phosphorylation of a 44 kDa protein(s), a series of
      taurine analogues were tested in an in vitro assay using a subcellular
      mitochondrial fraction of rat heart. Inhibitors of the phosphorylation of the 44
      kDa protein include taurine and close structural analogues of taurine such as
      aminoethylhydrogen sulfate and alpha-sulfo-beta-alanine. Secondary amines with
      the taurine structure partially locked into a saturated 5-membered ring such as
      (+/-)piperidine-3-sulfonic acid and 1,2,3,4-tetrahydroquinoline-8-sulfonic acid
      also possess inhibitory activity. Sulfone analogues of taurine such as 2
      aminoethylmethylsulfone, a non-restricted taurine analogue with maximal
      conformational flexibility about its amino and sulfone moieties, and (+/-)3
      aminotetrahydrothiopyran-1,1-dioxide, an analogue containing the sulfone moiety
      in a six-membered ring structure, were found to be more potent inhibitors of
      phosphorylation than taurine despite the fact that the sulfone moiety is neither
      an isosteric nor isoelectronic substitution for the sulfonic acid moiety. The
      results of this study indicate that the inhibition of the phosphorylation of the
      44 kDa protein in a rat heart mitochondrial fraction is relatively specific for
      the taurine structure. Two analogues of taurine with unsaturated rings containing
      a primary sulfonic acid and a secondary amine, pyridine-3-sulfonic acid and
      quinoline-8-sulfonic acid, were observed to be stimulators of the phosphorylation
      of the 44 kDa protein. In addition, 2-aminobenzenesulfonic acid also stimulated
      phosphorylation. Phase separation experiments with Triton X-114 suggest that the
      44 kDa phosphoprotein is a soluble protein and not an integral membrane protein
      of the mitochondria. Phosphate incorporation into specific amino acids was
      determined by two-dimensional electrophoresis on celluloses plates and was found
      exclusively in the serine residues.

PMID- 7731063
TI  - Essay on violence.

PMID- 7731062
TI  - Selective activation by atrial natriuretic factor of phosphatidylcholine-specific
      phospholipase activities in purified heart muscle plasma membranes.
AB  - We have characterized a membrane-bound phosphatidylcholine (PC) specific
      phospholipase C (PC-PLC) in plasma membranes from rat cardiac muscle, and have
      investigated the role of PC-PLC and PC-specific phospholipase D (PC-PLD)
      activities in the mechanism of action of atrial natriuretic factor (ANF). In
      purified sarcolemma, ANF stimulated over a wide range of concentrations with a
      maximum at 10(-11) M the hydrolysis of phosphatidylcholine through PC-PLD giving
      phosphatidate and choline, whereas higher concentrations of ANF (10(-10) M)
      preferentially stimulated PC breakdown through PC-PLC to form diacylglycerol and
      phosphocholine. To confirm the involvement of the PC-PLD in the mechanism of ANF
      action, we measured the transphosphatidylation reaction, a specific assay for
      this phospholipase which in the presence of ethanol catalyses the
      phosphatidylethanol formation from PC. ANF stimulated phosphatidylethanol
      formation with the same dose-response behavior as phosphatidate formation. The
      significant diacylglycerol increase at 10(-10) M ANF, in the presence of
      propranolol, a potent inhibitor of phosphatidate phosphatase which can hydrolyse
      phosphatidate to give diacylglycerol, suggested a direct involvement of PC-PLC.
      The use of GTP-gamma-S, a non hydrolysable analog of GTP, and of pertussis toxin
      showed the involvement of a pertussis toxin insensitive G protein in PC-PLC
      mediated ANF signal transduction. We suggest a differential effect of ANF on PC
      breakdown by phospholipases C and D depending on the concentration of the
      peptide.

PMID- 7731064
TI  - How HIV causes AIDS.

PMID- 7731065
TI  - Health-care reform: a physician's perspective.

PMID- 7731066
TI  - Emergency departments: an important component of public health.

PMID- 7731067
TI  - Clinical differences between pulmonary and extrapulmonary tuberculosis: a 5-year
      retrospective study.
AB  - This article describes the clinical, epidemiologic, laboratory, and treatment
      characteristics of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis
      (EPTB) in Eastern North Carolina, a primarily rural area. The database was
      obtained for 1988-1992 from the University Medical Center of Eastern North
      Carolina-Pitt County and East Carolina University School of Medicine (the
      tertiary care referral center for this region). One hundred thirty-eight culture
      positive patients were enrolled in the study; 56% were PTB and 44% were EPTB.
      African-American males constituted 59% of the population. Sixty-nine percent of
      the patient base were uninsured. There was a bimodal age distribution of < 40 and
      > 60 years of age. Factors associated with PTB (reported as odds ratios) were
      white males (2.5), diabetes mellitus (5.4), and cancer (5.1). Factors associated
      with EPTB (reported as odds ratios) were African-American females, positive human
      immunodeficiency virus (HIV) serology (8.7), low hematocrit (32.6), and elevated
      alkaline phosphatase (199). This study emphasizes that in the latest resurgence
      of tuberculosis, impoverished rural areas, which have been ignored in earlier and
      present control efforts, are important reservoirs of disease.

PMID- 7731068
TI  - Carpal tunnel syndrome: update.
AB  - Since reports in the late 1940s of surgical treatment for compressive neuropathy
      of the median nerve at the wrist, carpal tunnel release has become one of the
      most commonly performed surgical procedures. Despite the frequency of this
      surgery, controversy remains regarding diagnosis and management. Fifty
      consecutive surgically treated cases performed under local anesthesia. Ninety
      percent of patients (45/50) obtained complete relief of symptoms. The success
      rate is related to proper patient selection and complete division of the
      transverse carpal ligament under direct vision at surgery.

PMID- 7731069
TI  - The nutritional impact of breakfast consumption on the diets of inner-city
      African-American elementary school children.
AB  - To determine the contribution of breakfast-eating behavior to dietary adequacy
      among low-income African-American children, 1151 children attending grades two
      through five at four elementary schools in East Orange, New Jersey were studied.
      Results of a 4-day eating behavior survey and a 24-hour dietary recall reveal
      that on any given day, 12% to 26% of children attend school without having eaten
      anything. Thirty-six percent of the children were obese, which did not vary with
      breakfast-eating behavior. A significantly greater proportion of the children who
      skipped breakfast compared to those who ate breakfast failed to achieve dietary
      adequacy for nearly every nutrient studied. More than one third of breakfast
      skippers consumed < 50% of the recommended dietary allowance for vitamins A, E,
      B6, and folacin, and nearly one fourth consumed < 50% of the recommended dietary
      allowance for calories, vitamin C, calcium, and iron. Not eating breakfast
      results in substantial deficits in dietary intake of a variety of essential
      nutrients among low-income African-American school children. Efforts to improve
      the nutritional status of children should include nutrition education to promote
      breakfast.

PMID- 7731070
TI  - Violence as a barrier to compliance for the hypertensive urban African American.
AB  - Violence is now recognized as a health epidemic. Violence is especially prevalent
      in inner-city African-American communities. Most of the attention has focused on
      youths. However, the effects of violence extend to the communities' hypertensive
      patients. Patients are subjected to the emotional impact of violence on and
      individual level. Studies linking stress, with hypertension have not directly
      addressed the role of violence. As a group, they suffer from violence's diverting
      of funds in the health-care system. For this particular subgroup, violence is
      ingrained in their daily lives. Their coping mechanisms often place compliance
      with antihypertensive measures in jeopardy. Community intervention is needed to
      address the violence. However, primary care physicians in these communities must
      inquire about the impact violence has on their hypertensive patients to eliminate
      possible compliance barriers.

PMID- 7731071
TI  - Severe anemia: a risk factor for glomerular injury in sickle cell disease.
AB  - Approximately 15% to 20% of patients with sickle cell disease have proteinuria.
      Proteinuria, particularly albuminuria, is the hallmark of glomerular injury. This
      study examines risk factors for glomerular injury as indicated by urinary albumin
      excretion (UAE) 30 microgram/minute, directly related to sickle cell disease. A
      total of seven patients were enrolled between September 1992 and March 1993.
      Fasting blood chemistries, complete blood cell count, 24-hour urine for protein
      and creatinine clearance, and glomerular filtration rate determined by 125 I
      iothalamate were obtained for each patient. The results indicated that the lower
      the hematocrit, the higher the UAE rate. Low hematocrits have served as a
      protective mechanism in sickle cell disease by reducing blood viscosity and thus
      decreasing the number of vaso-occlusive crises. However, severe anemia appears to
      have an indirect adverse effect on the kidney in sickle cell disease.

PMID- 7731072
TI  - The prognostic significance of race and survival from breast cancer: a model for
      assessing the reliability of reported survival differences.
AB  - For more than 20 years, black women with breast cancer have been reported to have
      a lower survival rate than white women with breast cancer. Despite correcting for
      stage and socioeconomic status, some studies continue to report race-related
      excess mortality. A reliability scoring system was developed, based primarily on
      the precision of the staging system used, and the likelihood that the quality of
      treatment was comparable. Studies that compared the survival of blacks and whites
      treated for breast cancer from 1968 to 1988 were included in this study. Studies
      that demonstrated relatively large differences in the 5-year survival between
      blacks and whites were associated with low reliability scores. Studies that
      reported little or no difference in 5-year survival rates were associated with
      relatively high reliability scores. This model and the literature on which it is
      based suggest that the reported survival differences associated with race can be
      explained by differences in stage at presentation and by differences in the
      quality of care received. Efforts directed at early detection and improvements in
      the quality of care delivered are likely to reduce the excess breast cancer
      mortality experienced by black women.

PMID- 7731073
TI  - Hypernatremia in the aging: causes, manifestations, and outcome.
AB  - The incidence, clinical manifestations, morbidity, and mortality of all adult
      hypernatremic patients hospitalized during a 6-month period were studied. The
      impact of age on this parameter was evaluated, and the velocity of correction
      that produced best clinical results was established. Records of all patients who
      were admitted or developed hypernatremia (Na+ > 150 mEq/L) were reviewed.
      Demographic characteristics of age, gender, associated diagnosis, length of stay,
      source of admission, treatment, and outcome were recorded. Of 3209
      hospitalizations, 111 patients were hypernatremic (3.46%). Sixty-five were
      admitted with hypernatremia, and 45 developed hypernatremia while hospitalized.
      Fifteen had recurrent episodes of hypernatremia. Forty-nine had associated
      hypokalemia and six had hypercalcemia. The etiology was multifactorial and varied
      with age. Correction of the hypernatremia within 4 days produced significant
      improvement in mental status. The overall mortality was 48.6%, and age did not
      favorably influence mortality. Hypernatremia is a common disorder of elderly
      hospitalized patients, associated with high mortality and morbidity. Other
      electrolyte disorders that impair the kidney concentrating ability frequently are
      observed. The etiology is multiple, and febrile illness due to bacterial
      infections is the most common cause among the elderly. Prompt treatment of
      infections and increased water intake in this group of patients could prevent its
      development. Correction over a 72-hour period significantly improved recovery of
      mental functions.

PMID- 7731074
TI  - Intramuscular Toradol, gastrointestinal bleeding, and peptic ulcer perforation: a
      case report.
AB  - Peptic ulcers, perforations, and serious gastrointestinal bleeding have not been
      reported with intramuscular ketoralac tromethamine, the first parenteral
      nonsteroidal anti-inflammatory drug available for analgesic use. This article
      presents the case of a 39-year-old black female who underwent surgical repair of
      a perforated gastric ulcer after receiving multiple dosages of intramuscular
      ketoralac tromethamine in the emergency room over a period of 21/2 months for the
      treatment of pain due to chronic pancreatitis.

PMID- 7731075
TI  - A brief history of the orthopedic section of the National Medical Association.

PMID- 7731076
TI  - Communications to the annual conference of the British Association of Sport and
      Exercise Sciences (BASES). Aberdeen, Scotland, 18-21 July 1995. Abstracts.

PMID- 7731077
TI  - Drug resistance in Helicobacter pylori.

PMID- 7731078
TI  - Antibodies to the extractable nuclear antigens (ENA) in Pakistani patients with
      systemic rheumatic disease.
AB  - Autoantibodies to the saline extracts of cells are being used as diagnostic and
      prognostic markers in the investigation of patients with suspected systemic
      rheumatic disease. These are also called antibodies to the extractable nuclear
      antigens or anti ENA antibodies. We used saline extracts of human spleen cells
      and rabbit thymus extract to detect six subtypes of anti ENA antibodies, namely
      anti SSA (anti Sjogren's syndrome A), anti SSB (anti Sjogren's syndrome B), anti
      RNP (anti Ribonucleoprotein), anti Sm (anti Smith), anti Jo-1 (anti Jo-1) and
      anti Scl 70 (anti Systemic sclerosis 70) antibodies. Two hundred and thirty-seven
      patients' sera were screened in the department of Immunology, Armed Forces
      Institute of Pathology (AFIP), Rawalpindi, over a period of 16 months. Fifty
      seven were positive for auto antibodies, of which 26 had anti SSA antibodies, 12
      anti SSA+ anti RNP+ anti Sm antibodies, 7 anti RNP+ anti Sm antibodies, 6 anti
      SSA+ anti SSB antibodies, 5 anti SSA+ anti RNP antibodies while one patient
      showed only anti RNP antibody. The detection of the anti ENA antibodies was
      specially helpful in diagnosing patients with systemic lupus erythematosis
      presenting with atypical features and with mixed connective tissue disease.

PMID- 7731079
TI  - Vaginal thrush and its management in pregnancy.
AB  - The frequency of vaginal thrush was determined in an unselected group of patients
      attending the antenatal clinic. Diagnosis was based on phase-contrast microscopy
      and culture. One hundred and two patients were initially included but only 98
      completed this study. Thrush infection was detected in 25 (25%) patients. All 25
      patients underwent treatment with one vaginal ovule containing 400 mg
      ketoconazole on each of three successive evenings. Thrush attack was eliminated
      in 23 (92%) cases. In view of the virtual absence of clinical symptoms, the
      recommendation to undertake general screening for thrush in pregnancy is
      discussed. The efficacy of treatment with ketoconazole ovules was studied and the
      results of treatment were reviewed after 4 and 8 weeks. Recurrence or re
      infection has to be considered in pregnancy so that thrush treatment should
      sensibly be undertaken in the third trimester unless subjective symptoms indicate
      the need for earlier therapy.

PMID- 7731080
TI  - Effectiveness of percutaneous nephrostomy in reversing obstructive renal failure.
AB  - A retrospective analysis of 34 patients of obstructive renal failure, initially
      managed by percutaneous nephrostomy was performed. Pre procedure blood
      biochemical profile was compared with upto one week follow-up of blood chemistry.
      There was a decline of 71.1% and 56.08% (P-values 0.0001 and 0.0028) in the mean
      values of serum creatinine and blood urea nitrogen respectively at 7 days after
      the procedure. Improvement in blood biochemical profile was solely dependent on
      performance of percutaneous nephrostomy.

PMID- 7731081
TI  - Antibiotic resistance: epidemiology and strategies for prevention.

PMID- 7731082
TI  - Helicobacter pylori clearance and eradication with triple therapy in duodenal
      ulcer patients.
AB  - Triple therapy was given to 49 chronic helicobacter pylori positive chronic
      duodenal ulcer cases to see its efficacy in H. pylori clearance, eradication and
      ulcer healing. H. pylori clearance and eradication rates at week 5 and 8 were
      87.8% and 81.5% while ulcer healing rates 68.2% and 81.5% respectively. Seven
      (18%) cases failed to clear H. pylori and were classified as non-responders.
      Histologically 60% showed post-treatment regression of gastritis. Tolerance to
      drugs was excellent with a good compliance rate.

PMID- 7731083
TI  - Partial lipodystrophy and successful pregnancy outcome.

PMID- 7731084
TI  - HIV-I infection in a family blood donor.

PMID- 7731085
TI  - Seroprevalence of Toxoplasma gondii in domestic animals in Pakistan.
AB  - The seroprevalence of Toxoplasma gondii infections among food animals in South
      West Pakistan was measured by serological examination using a commercial latex
      agglutination test (LAT). In all 262 blood samples, from 100 cattle, 40 sheep, 58
      goats and 64 chickens, were collected from the city abattoir. Titers considered
      diagnostically significant (> or = 1:64) were detected in 25% of cattle and 2.5%
      of sheep. None of the goats and chickens presented seropositivity for anti
      toxoplasma antibodies. The study suggests the need for further investigations to
      determine the impact of these findings on the human population.

PMID- 7731086
TI  - Surgery for bleeding esophageal varices.
AB  - A total of 72 patients were operated for bleeding esophageal varices over five
      years. Cause of portal hypertension was cirrhosis in 33, Schistosomal fibrosis in
      23 and a combination of the two diseases in 3 cases. Biopsy was not available in
      13 patients. Fifty-eight patients were child grade A and B, while 14 patients
      were grade C. Overall, there were 16 hospital deaths (22.2%) and 28 patients had
      complications (38.8%). Specifically, Hassab's operation was done in 40 patients
      with 12.5% mortality and 11.7% incidence of rebleeding. Hassab's operation plus
      esophageal transection in 13 patients was associated with 46.1% mortality and no
      incidence of rebleeding. Warren's splenorenal shunt, done in 11 patients, was
      accompanied by 1 (9%) death and no incidence of rebleeding. Mortality rate
      increased significantly when esophageal transection was added to Hassab's
      operation. It is concluded that for low risk patients being operated electively,
      Warren's shunt is an acceptable alternative to Hassab's operation which is better
      suited to emergency situations. Esophageal transection should not be added to
      Hassab's operation because this increases the mortality.

PMID- 7731087
TI  - Pneumatic lithotripsy: a new modality for treatment of ureteric stones.
AB  - Two hundred and twenty ureteric stones in 214 patients were fragmented
      intracorporeally by pneumatic lithotripsy under general/regional anaesthesia in a
      day care set-up. Patients were followed-up weekly and retreatment was done at 4
      weeks where necessary. Majority (77%) of patients were in the age group 21-40
      years with a male to female ratio of 2:1. Stone location was 86% in the lower
      third, 11% in the middle and 3% in the upper third ureter. Size of stones was
      less than 6 mm in 14%, 7-12 mm in 67% and more than 20 mm in 4% cases. All 81%
      stones of < 12 mm were fragmented in one treatment session while single treatment
      rate for stones 13-18 mm was 85% and 44% for more than 20 mm size. Overall non
      fragmentation rate was 0.9%. Stone free state at four weeks was 95%.
      Complications were observed in 8.6% cases which included urosepsis, haematuria
      and perforations. Infrared spectroscopy (IR) in 45 stones showed majority (64%)
      to be composed of calcium oxalate. Our experience shows that PL is a safe and
      effective means of performing intracorporeal lithotripsy for both large and hard
      ureteric stones.

PMID- 7731088
TI  - [Establishment of a new scirrhous gastric cancer cell line OCUM-2M from a primary
      gastric tumor].
AB  - We report on the establishment and characterization of a scirrhous gastric cancer
      cell line, designated OCUM-2M, derived from a 49-year-old Japanese female. OCUM
      2M was derived from a primary tumor of stomach taken by total gastrectomy. The
      cell line grew singly or in clusters in the cultured medium. The cell line
      continued to multiply for more than one year. Doubling time was 37.3 hours,
      chromosomal mode was 70. The DNA ploidy pattern was aneuploid and DNA index was
      1.59. It produced several tumor-associated antigens such as CEA, CA19-9, SLX and
      SPan-1. The cell line was transplantable in athymic BALB/c nude mice, and
      histological findings of the xenografted tumor showed poorly differentiated
      adenocarcinoma. The growth of OCUM-2M was stimulated following the addition of
      EGF, b-FGF and KGF, and decreased following the addition of TGF-beta 1. This cell
      line is useful in vitro and in vivo systems for studies of the biology of
      scirrhous gastric carcinoma.

PMID- 7731089
TI  - [Cell proliferation and cell death (apoptosis) as indices differentiating
      malignant from benign gastrointestinal myogenic tumors].
AB  - We examined whether the determination of cell proliferation and cell death rates
      was useful in the differential diagnosis between benign and malignant myogenic
      tumors of gastrointestinal tract. As markers for cell proliferation and cell
      death, Ki-67 (MIB-1) positive rates or argyrophilic nucleolar organizer region
      (AgNOR) counts and apoptotic cell counts were determined in a total of 53
      myogenic tumors comprising 36 leiomyomas and 17 leiomyosarcomas. Apoptotic cells
      were detected with the in situ nick end labeling method reported by Gavrieli in
      1992 with modifications. Significant differences were observed in the Ki-67
      positive rates (leiomyoma 1.8 +/- 1.4%, leiomyosarcoma 8.6 +/- 6.0%, p < 0.0001),
      in the mean AgNOR counts (leiomyoma 1.77 +/- 0.53, leiomyosarcomas 3.14 +/- 1.02,
      p < 0.0001), and in the apoptotic cell counts (median; leiomyoma 3.2,
      leiomyosarcoma 32.5 per 10(6) tumor cells, p < 0.005). All high grade sarcomas
      were picked up by the Ki-67 index of more than 7%, and almost all leiomyomas were
      thrown away by the AgNOR counts more than 3.0 within the low Ki-67 cases, which
      showed 81% of sensitivity and 97% of specificity. These results show that a
      combination use of Ki-67 and AgNOR is of use in the differential diagnosis
      between leiomyoma and leiomyosarcoma. Although a significant difference was also
      noted in apoptotic cell counts between these two categories, this seems not to be
      a practical index for the discrimination because apoptotic cell death is a rare
      event in gastrointestinal myogenic tumors.

PMID- 7731090
TI  - [Portal hemodynamic changes from TIPS--evaluation with pulse Doppler method].
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) was applied in three
      patients with Child C liver cirrhosis. Portal venous pressure was reduced by an
      average of 10.7 mmHg, and results such as the disappearance of esophageal varices
      and reduction in ascites were obtained. The portal hemodynamics of these three
      patients was observed before and after TIPS using the pulse Doppler method. When
      portal hemodynamics in the main portal vein was examined before TIPS, it was
      found that the mean blood flow velocity had decreased, the blood flow volume was
      reduced and the cross-sectional area of the vein had increased. The congestion
      index was high and there was definite congestion of the portal venous system.
      After TIPS, the blood flow velocity and volume increased, the cross-sectional
      area of the vein was reduced and the congestion index was lower. Congestion of
      the portal venous system was improved in these three patients and the clinical
      efficacy of TIPS was proven by these results. If the stent can be detected
      sonographically, stent patency is easily confirmed with the pulse Doppler method
      which is usefull examination technique for follow-up of patients undergoing TIPS.

PMID- 7731091
TI  - [Measurement of bile acid N-acetylglucosaminides in serum and urine of patients
      with chronic liver diseases during ursodeoxycholic acid treatment].
AB  - Bile acid N-acetylglucosaminide (GlcNAc) was investigated in serum and urine of
      patients with chronic liver diseases during ursodeoxycholic acid (UDCA) treatment
      by HPLC. Bile acid N-acetylglucosaminide was not detected other than primary
      biliary cirrhosis in serum and urine. All of these N-acetyglucosaminide was
      ursodeoxycholic acid N-acetylglucosaminide (GlcNAc-UDCA). GlcNAc-UDCA excretion
      was 17.3 +/- 5.7 mg/day in PBC stage I, 12.1 +/- 5.4 mg/day in stage II, 39.1 +/-
      20.8 mg/day in stage III. Among the GlcNAc fraction GlcNAc-UDCA-gly occupied
      greatest part followed by GlcNAc-UDCA-tau and non-amidated Glc-NAc-UDCA. GlcNAc
      UDCA was 50.1% of total urinary bile acids excretion in PBC stage I, 32.5% in
      stage II, 20.5% in stage III. However, GlcNAc-UDCA was less than 2.5% of total
      serum bile acids in every stage. These results indicate that N-acetylglucosamine
      conjugation is one of the major pathway of UDCA in patient with primary biliary
      cirrhosis.

PMID- 7731092
TI  - [A case of giant intramural hematoma of the esophagus after vomiting].

PMID- 7731093
TI  - [Simultaneous occurrence of cystadenocarcinoma of the liver and gastric cancer].

PMID- 7731094
TI  - [Duplication of ascending colon with heterotopic gastric mucosa--report of a
      case].

PMID- 7731095
TI  - [A case of mesenteric leiomyosarcoma with giant abscess].

PMID- 7731096
TI  - [A case of primary rhabdomyosarcoma of liver at autopsy--literature review of 7
      cases reported in Japan].

PMID- 7731097
TI  - [A case of antimitochondrial antibody (AMA) negative primary biliary cirrhosis
      (PBC) associated with Sjogren's syndrome and arthropathy].

PMID- 7731098
TI  - [13C-urea breath test for the detection of Helicobacter pylori infection and the
      assessment of therapeutic effect].

PMID- 7731099
TI  - [Effect of total proctocolectomy with ileal pouch-anal anastomosis on metabolism
      of active vitamin D in dogs].

PMID- 7731100
TI  - [Detection of Helicobacter pylori using Ota's procedure and mucous
      immunohistochemistry].

PMID- 7731101
TI  - [Effect of acarbose in non-insulin dependent diabetes mellitus with dumping
      syndrome after gastrectomy].

PMID- 7731102
TI  - [MAP kinase cascade in cultured rat mesangial cells].
AB  - In order to evaluate the intracellular signaling pathway of endothelin 1 (ET-1),
      we examined mitogen-activated protein kinase (MAPK) cascade in cultured rat
      glomerular mesangial cells. Treatment of quiescent mesangial cells with ET-1
      increased kinase activities toward bovine myelin basic protein (MBP). Maximal
      activation was at 10 min and ED50 was about 5 nM. The 44- and 42-kDa kinases were
      activated in MBP containing gel kinase assay. These kinases were identified as
      extracellular signal regulated kinase (ERK) 1 and ERK2 with immunoblotting,
      respectively. MAPK or ERK kinase (MEK), one of the MAPK kinases, was present in
      rat mesangial cells and ET-1 also activated this MAPK kinase. These results
      indicate that MAPK kinase and MAP kinase are rapidly activated by ET-1 and may
      modulate cellular functions in rat mesangial cells.

PMID- 7731103
TI  - [Primary culture of proximal tubular cells (PTC) from normal mouse kidney as an
      in vitro model to study mechanisms of development of tubulointerstitial
      nephritis. Induction of ICAM-1 in PTC by antigen-primed lymphocytes].
AB  - Cultured PTC clearly expressed intercellular adhesion molecule-1 (ICAM-1) under
      the influence of tubular basement membrane antigen (TBM)-primed lymphocytes.
      These TBM-primed lymphocytes also demonstrated a high cytotoxic activity against
      cultured PTC. A pure preparation of isolated PTC from BALB/c mouse kidney was
      brought into primary culture. PTC was prepared by the method of Boogaard PJ et
      al, and our modification. Briefly, kidney was perfused with buffer containing
      0.08% (w/v) collagenase. The cortical tissue was then filtered through nylon
      gauze. Viable PTC were separated from other materials by isopycnic centrifugation
      on a discontinuous Nycodenz gradient. The confluent monolayer of PTC showed a
      typical epithelial morphology with cobblestone-like cells in the center of the
      cell-islands. Typical dome formation was observed in PTC cultures. These cells
      also strongly expressed gamma-glutamyl transpeptitase activity. Coculture of PTC
      with syngeneic lymphocytes primed with TBM antigen induced ICAM-1 expression in
      PTC. The TBM-primed lymphocytes had a cytotoxic activity without complement.
      However, neither virgin lymphocytes nor liver antigen-primed lymphocytes had
      cytotoxic activity. This simple syngeneic experimental model may allow us further
      molecular biological examination of renal tubulointerstitial diseases.

PMID- 7731104
TI  - [The ameliorative effect of probucol on adriamycin (ADR) induced nephrotic rats].
AB  - This paper reports the ameliorative effect of Probucol (Pb) on ADR-induced
      nephrotic rats. Male Wistar rats underwent unilateral nephrectomy followed by one
      week subsequent intravenous injection of 4.0 mg/kg of ADR. The rats were then
      divided into 3 groups: Pb-treated, non-treated and the control. The control group
      received 0.9% saline (vehicle) by injection. The 24-hr urinary protein excretion
      was measured for 24 weeks. When the animals were sacrificed at weeks 4, 12, and
      24, respectively, blood samples were collected for biochemical study and the
      kidneys were extracted for measurement of malondialdehyde (MDA). In the
      morphological study, glomerular volume, glomerular sclerosis in dex (GSI), and
      tubulointerstitial index (TII) were calculated. Pb treatment lowered the serum
      lipid level and 24-hr urinary protein excretion. Total cholesterol was closely
      correlated with the urinary protein. However, there was no difference in terms of
      glomerular volume, kidney weight and GSI between the two groups. Pb treatment
      suppressed the kidney tissue MDA and TII significantly, the values of which were
      mutually correlated. The 24-hr protein excretion was significantly correlated
      with TII, but not with GSI. The decreased proteinuria was explained on the basis
      of suppression of enhancement of intraglomerular pressure induced by interstitial
      lesion. The findings suggest that renoprotection of Pb may derive from the
      amelioration of interstitial lesions.

PMID- 7731105
TI  - [Relative hypoparathyroidism associated with CAPD treatment using normo-calcemic
      (3.5mEq/1) dialysate: an approach from transperitoneal calcium balance].
AB  - We investigated factors affecting net transperitoneal calcium balance (Ca-BL) and
      the level of parathyroid hormone in relation to stepwise changes in serum
      calcium, by short PET (peritoneal equibrium test during 240 min: using 2000 ml of
      2.5% dextrose dialysate containing 1.75 mmol/L Ca) in uremic patients undergoing
      stable CAPD. We calculated Ca-BL (mg/effluent/PET) of 244 effluents obtained from
      90 patients receiving calcium carbonate as a phosphate binder without vitamin D
      supplementation. Their serum calcium level corrected with albumin (cSCa),
      alkaline phosphatase activity (ALP) and intact-PTH level was 9.7 +/- 0.9 mg/dl,
      236 +/- 83 mIU/ml and 153.0 +/- 172.4 pg/ml, respectively. We proposed two
      statistic significant regression lines between Ca-BL and total drainage effluent
      volume (Ca-BL = 133X - 0.056: r = 0.981, P < 0.001), cSCa (Ca-BL = -12.9X +
      123.6: r = 0.941, P < 0.01). Total drainage volume (TDV) and cSCa were two major
      factors affecting Ca-BL. A TDV level of 2430 ml/240 min-PET or more was required
      for positive Ca-BL in cases with 9.5-10.0 mg/dl of cSCa, using this linear
      regression analysis. A cSCa level of 9.6 mg/dl or more was also required for
      positive Ca-BL in cases with 2400-2600 ml/240min-PET. We also proposed a
      significant linear regression line between the intact-PTH level and cSCa (i-PTH =
      -90.5X + 1015.8, r = 0.973, P < 0.01). This line suggest that 200 pg/ml of intact
      PTH was obtained by 9.0 mg/dl or less of cSCa level in 90 CAPD uremic
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731106
TI  - [Cytokine mRNA expression in peripheral blood mononuclear cells from hemodialysis
      and CAPD patients].
AB  - Inflammatory cytokines, including TNF-alpha, IL-1 beta and IL-6, have been
      reported to be responsible for acute or chronic complications and
      biocompatibility issues in dialysis patients have focused on the role of these
      cytokines. Expression of mRNA for TNF-alpha, interleukin (IL)-1 beta and IL-6 in
      peripheral blood mononuclear cells (PBMC) and their plasma concentrations was
      examined in 10 hemodialysis and 10 continuous ambulatory peritoneal dialysis
      (CAPD) patients. Plasma TNF-alpha and IL-1 beta levels in hemodialysis, CAPD and
      in every healthy subject were below the detection limits. Plasma IL-6
      concentration was increased significantly in hemodialysis and CAPD patients when
      compared to normal controls (p < 0.01). Expression of mRNA for TNF-alpha, IL-1
      beta and IL-6 in PBMCs was increased significantly (p < 0.01) in hemodialysis and
      CAPD patients compared to normal subjects. These mRNA expressions were lower in
      CAPD patients than in hemodialysis patients (p < 0.05). Significant correlation
      was observed between the plasma IL-6 concentration and PBMC IL-6 mRNA expression
      in patients on hemodialysis or CAPD (p < 0.01). IL-6 mRNA expression in PBMCs did
      not correlate with the duration of hemodialysis or CAPD, blood urea nitrogen
      (BUN) or serum creatinine levels. These findings suggest that mRNA expression
      indicates stimulation by dialysis procedures in patients, and CAPD is tolerated
      better than hemodialysis by patients with end-stage renal failure.

PMID- 7731107
TI  - [The effects of recombinant human growth hormone (r-hGH, SM-9500, genotropin) on
      growth failure in children with uremia. Japanese Multi-Center Study (Genotropin)
      Group on Children with Renal Disease].
AB  - We treated 90 pediatric patients with chronic renal failure with recombinant
      growth hormone (r-hGH) for 12 months to improve their growth retardation due to
      uremia. They were divided into two groups, non-dialyzed and dialyzed children.
      The dose of r-hGH was 0.5 or 1.0 IU/kg/week in dialyzed children. After 12 months
      of the treatment using r-hGH, growth velocity was significantly increased in any
      group of children. Growth velocity was stimulated to about twice as much as
      before treatment (that were: in non-dialyzed group, 4.2 +/- 2.6cm/year vs. 6.2 +/
      2.0cm/year, P < 0.05, in dialyzed children treated with 0.51U of r-hGH: 2.7 +/-
      1.8cm/year vs. 5.2 +/- 2.6cm/year, P < 0.001, and in dialyzed children treated
      with 1.01U of r-hGH: 3.0 +/- 1.5cm/year vs. 6.3 +/- 2.2cm/year, P < 0.001). No
      severe side effects was noted and no disturbance of renal function. Our results
      were consistent with those reported from Europe and USA. We conclude that r-hGH
      treatment is very effective in improving retarded growth in children with renal
      disease.

PMID- 7731108
TI  - [The effects of recombinant human growth hormone (r-hGH, SM-9500, genotropin) on
      growth disturbance in children after renal transplantation. Japanese Multi-Center
      Study (Genotropin) Group on Children with Renal Disease].
AB  - We treated 27 children with renal transplantation who showed growth failure due
      to deteriorated graft function and/or corticosteroids therapy with recombinant
      growth hormone (r-hGH) to improve their growth disturbance. The dose of rhGH was
      either 0.5 or 1.0 IU/kg/week. After 12 months treatment of r-hGH, growth velocity
      was significantly increased in both groups. Growth velocity was improved from 5.0
      +/- 2.9 cm/year to 7.7 +/- 2.3 cm/year, P < 0.05, in 0.51U group and 3.7 +/- 2.4
      cm/year to 6.3 +/- 3.3 cm/year, P < 0.05, in 1.01U group. The most important side
      effect of r-hGH was relevant to graft function. 7 out of all 27 children showed
      deterioration of graft function. However only 2 children showed significant
      decreases in their graft function during r-hGH therapy. Thus we conclude that r
      hGH therapy was effective to improve growth failure in uremic children even after
      renal transplantation due to poor graft function and/or corticosteroids therapy.

PMID- 7731109
TI  - [A case of erythropoietic protoporphyria associated with tubulointerstitial
      disease and dilated cardiomyopathy].
AB  - A 34-year-old female patient was admitted to our hospital with a 1-year history
      of chronic congestive heart failure, massive proteinuria and tibial edema. On
      admission, she presented with hemolytic anemia, hepatomegaly, splenomegaly and
      renal impairment. Furthermore, the skin of her face, hand, forearm, lower
      extremities showed crust and bulla. Laboratory examination revealed a large
      amount of protoporphyrin in her blood and feces, but no increase in urine. Light
      microscopy of renal biopsy showed moderate chronic tubulointerstitinal disease
      and mild proliferation of mesangial cells. The prophyians are a group of
      compounds associated with involving the disturbance of various biosynthetic heme
      pathwas. Until now, the regulation of porphyrin and heme metabolism in the kidney
      have received relatively little attention as compared with those in liver and
      erythropoietic tissue. However, some recent reports have confirmed that proximal
      tubular cells may contribute to heme biosynthesis. It was strongly suggested that
      chronic tubulointerstitinal injury in this case might be directly induced by the
      disturbance of the biosynthetic heme pathway in the tubules.

PMID- 7731110
TI  - [A case of progressive systemic sclerosis with crescentic glomerulonephritis
      associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)
      and anti-glomerular basement membrane antibody (anti-GBM Ab)].
AB  - A 42-year-old female with progressive systemic sclerosis (PSS) developed rapidly
      progressive renal insufficiency. Renal pathology revealed crescentic
      glomerulonephritis (CrGN) without mucoid intimal proliferation of the
      interlobular arteries and fibrinoid necrosis of the afferent arterioles.
      Immunofluorescent micrography showed linear deposition of IgG along the
      glomerular capillary wall. Not only anti-glomerular basement membrane antibody
      (anti-GBM Ab), but also myeloperoxidase-antineutrophil cytoplasmic antibody (MPO
      ANCA) were simultaneously detected by an enzymelinked immunosorbent assay
      (ELISA). She did not develop pulmonary hemorrhage. These findings were compatible
      with ANCA-related vasculitis and anti-GBM Ab nephritis. Laboratory findings
      showed rapid elevation of serum creatinine level (over 6.0mg/dl), a high titer of
      MPO-ANCA (660.7 ELISA unit/ml) and anti-GBM Ab (409 units). Therefore, she was
      started on methylprednisolone pulse therapy and temporary hemodialysis. After
      immunosuppressive therapy, both antibodies titers had fallen to within the normal
      range. However, end-stage renal failure did not improve and maintenance
      hemodialysis was introduced. Recently, six patients of PSS with MPO-ANCA were
      first reported in Japan. These autoantibodies detected in this case strongly
      suggested that there may be associations between anti-GBM Ab nephritis and ANCA
      related vasculitis and PSS.

PMID- 7731111
TI  - [Pulmonary complications in patients with rheumatoid arthritis].
AB  - Pulmonary manifestations of rheumatoid arthritis were studied in 26 patients.
      Pulmonary complications could be divided into four subgroups: Interstitial
      pneumonia/Pulmonary fibrosis (n = 18), Bronchiolitis Obliterans Organizing
      Pneumonia (n = 4), Bronchiolitis Obliterans (n = 2), and Pleuritis/Pericarditis
      (n = 1). Analysis of cells in broncho-alveolar lavage fluid (BALF) revealed
      abnormally high percentages of lymphocytes in one-half of the patients and
      abnormally high percentages of neutrophils in one-third of the patients. The
      percent of BALF cells that were neutrophils was higher with higher chest
      radiograph grades. Analysis of soluble constituents of BALF indicated local
      production of IgG in two cases, but IgM-rheumatic factor was not detected. In 18
      of 26 patients corticosteroid or immunosuppressive drugs were needed, and most of
      the patients responded to the therapy and had good outcomes. The conditions of 6
      patients with interstitial pneumonia/pulmonary fibrosis deteriorated and 4
      patients died of progressive respiratory failure. The subclassification of
      rheumatoid lung was useful for predicting its outcome.

PMID- 7731112
TI  - [Changes in smooth muscle cell proliferation in pulmonary arteries of rats given
      monocrotaline].
AB  - To study the relationship between proliferation of smooth muscle cells and
      structural changes in arteries of rats given monocrotaline, light microscopy with
      immunohistochemistry for bromodeoxyuridine (BrdU) was done after a single
      subcutaneous injection of monocrotaline. In increase in DNA synthesis in smooth
      muscle cells was seen from 3 days until 14 days after administration. Since this
      increase was seen before pulmonary hypertension and medial thickness developed
      some mechanisms that induce proliferation of pulmonary atrial smooth muscle may
      have been triggered soon after monocrotaline injection.

PMID- 7731113
TI  - [Interferon production in peripheral blood cells of patients with pulmonary
      mycobacterial disease].
AB  - Production of interferon (IFN)-alpha and IFN-gamma were examined in 31 patients
      with acute tuberculosis, 12 patients with atypical mycobacterial disease. IFN
      production was examined in cultures of unseparated fresh whole blood. Production
      of IFN-alpha was induced by hemagglutinating virus of Japan and production of IFN
      gamma was induced by PHA. Patients with mycobacterial disease produced
      significantly less IFN-alpha than healthy subjects. In patients with acute
      tuberculosis, effective chemotherapy for 2 months restored IFN-alpha production.
      Patients produced less IFN-gamma than healthy subjects, but the difference was
      not significant. Patients with high serum CRP levels tended to produce little IFN
      alpha. These results suggest that measurement of IFN production is useful for
      immunological evaluation of patients with mycobacterial disease.

PMID- 7731115
TI  - [Survey of the state of bronchography in Japan].
AB  - Bronchography is not routinely done. We analyzed the state of bronchography with
      questionnaires returned from 57 hospitals. Bronchography is now done at 30
      hospitals. The number done in 1992 ranged from 1 to 27 (median 3). Peripheral
      lung cancer and bronchiectasis were the two most frequent diseases for which
      bronchography was done. In other hospitals, bronchography was once done, but had
      been stopped. Two reasons for discontinuation of bronchography are: recent
      progress in radiographic diagnostic techniques such as high resolution CT, and
      discomfort of the patient. Now that propyliodone is no longer available, some
      hospitals may use iopydol-iopydone or iopamidol instead. It is necessary to
      elucidate the true need for bronchography and for an appropriate contrast medium
      to take the place of propyliodone.

PMID- 7731114
TI  - [Hydraulic conductivity of the visceral pleura with hemodynamic lung edema in
      dogs].
AB  - Hydraulic conductivity of the visceral pleura was measured in situ in
      anesthetized dogs. There were two groups: control (n = 7), and edema (n = 5). The
      7th intercostal space of the left thorax was opened. In each group, a
      hemispherical capsule, filled with physiological salt solution, was attached to
      the visceral pleura of left lobe by negative pressure made with a vacuum pump. In
      the edema group, pulmonary venous pressure was increased by ligation of the
      pulmonary vein. The transpleural fluid flow (V) was measured at different
      intracapsular pressures (delta P). The hydraulic conductivity was calculated from
      the relation between the fluid flow rate (v) and the intracapsular pressure,
      i.e., the slope of the linear regression line. The hydraulic conductivities in
      the control and edema groups were 1.49 +/- 0.68 and 3.19 +/- 1.13 nL.min-1.cmH2O
      1.cm-2, respectively. We conclude that the pleural tissue may play an important
      role in hydraulic conductivity of the visceral pleura when pulmonary venous
      pressure is high.

PMID- 7731116
TI  - [Possible involvement of smoking in the development of asthma-like conditions in
      patients with chronic obstructive pulmonary disease].
AB  - Indicies of asthma were measured in smokers with chronic bronchitis (CB) +
      pulmonary emphysema (PE), smokers with CB only, and non-smokers with CB, to
      examine whether smoking is involved in the development of asthma-like condition
      in patients with chronic obstructive pulmonary disease (COPD). Airway
      hypersensitivity was measured with an Astrograph method, and the reversibility of
      airway obstruction was measured as improvement in FEV1.0 and as percent change in
      FEV1.0 after inhalation of a beta-agonist. Both hypersensitivity and
      reversibility were significantly higher in smokers with CB+PE and in smokers with
      CB only than in non-smokers with CB. The number of eosinophils in sputum, but not
      in peripheral blood, was slightly higher in the smokers than in the non-smokers.
      The serum levels of IgE were significantly higher in the smokers than in the non
      smokers. No significant difference in the rate of positive skin tests for common
      allergens was observed among the three groups, but the rate of positive tests for
      Broncasma Berna was very high in the smokers, and all such tests were negative in
      the non-smokers. These results indicate that among patients with COPD an
      asthmatic component is more frequently found in smokers than in non-smokers, and
      suggest that smoking plays some part in the development of asthma-like condition
      in these diseases.

PMID- 7731117
TI  - [Chronic sinusitis among family members of patients with diffuse
      panbronchiolitis].
AB  - The frequency of chronic sinusitis among the family members of 26 patients with
      diffuse panbronchiolitis were analyzed, and were compared with the frequency in
      127 control families. In the diffuse panbronchiolitis group, 50% of families
      suffered from chronic sinusitis, in contrast to 18.9% of families in the control
      group. The difference was significant. Analysis of HLA antigens in families of
      patients with diffuse panbronchiolitis revealed that family members with chronic
      sinusitis had the same HLA haplotype as these patients with diffuse
      panbronchiolitis in the same family. These results indicate that patients with
      chronic sinusitis only and those with diffuse panbronchiolitis have similar
      genetic background. They also suggest that the patients with chronic sinusitis
      may be seen as a mild or incomplete type of diffuse panbronchiolitis.

PMID- 7731118
TI  - [Progressive pulmonary fibrosis in a case of Sjogren's syndrome with asbestos
      exposure].
AB  - A 62-year-old man had an occupational history of exposure to asbestos for 27
      years (1947-1974). Dry mouth, dry eyes and swollen gums were noted in 1974.
      Sjogren's syndrome was diagnosed in 1975. The chest radiograph in 1984 showed
      bilateral pleural thickening and small reticular opacities in the left lower lung
      field. In 1990, he complained of dyspnea and cough, and diffuse interstitial
      pneumonia was diagnosed. While being treated for diffuse interstitial pneumonia,
      pulmonary fibrosis progressed rapidly, and advanced pulmonary fibrosis was
      obvious in 1992. Laboratory data showed hyper gamma-globulinemia (36.8%) and a
      high level of IgG (3772 mg/dl) in 1976. These values decreased to within the
      normal ranges during the subsequent clinical course. The results of lymphocyte
      subset counts in 1988 were normal. With the progression of diffuse interstitial
      pneumonia in 1990, the lymphocyte subset counts showed a low percentage of CD4
      (19.2%), a low CD4/8 ratio (0.46), and a low percentage of CD20 (26.8%). In 1992,
      as pulmonary fibrosis progressed despite treatment, the disorder of lymphocyte
      subsets became worse. The CD4 percentage was very low (5.0%), as was the CD4/8
      ratio (0.08), and the percentage of CD20 (1.4%); the CD8 percentage was high
      (64.7%), as was the percentage of Leu 7 (49.0%). These immunologic and pulmonary
      changes could be not explained by Sjogren's syndrome. Determining what factor
      induced these changes is difficult, but asbestos exposure is a likely cause.

PMID- 7731119
TI  - [A case of pulmonary thrombosis associated with primary antiphospholipid
      syndrome].
AB  - A 23-year-old man was admitted because of an attack of chest pain and dry cough.
      Chest roentogenogram showed a solitary pulmonary nodule in the left upper lobe.
      Chest CT showed a nodule and a small pleural effusion on the same side. Pulmonary
      thrombosis was diagnosed by pulmonary Ventilation/perfusion scintigraphy and
      pulmonary arteriography. Deep vein thrombosis was not detected except in a distal
      pulmonary artery. The solitary nodule disappeared spontaneously without
      thrombolytic therapy. An anticardiolipin antibody (IgG) test was positive.
      Primary antiphospholipid syndrome was diagnosed, because of the absence of
      physical findings suggesting other collagen vascular diseases. Patients with
      antiphospholipid syndrome have a high frequency of pulmonary complications that
      include pulmonary hypertension and pulmonary embolism. Most of the patients with
      pulmonary embolism have deep vein thrombosis, and pulmonary vessel thrombosis as
      seen in the present case is a rare complication.

PMID- 7731120
TI  - [A case of cilostazol-induced pneumonitis].
AB  - A 73-year-old man had been treated with cilostazol for antithrombotic therapy
      after a myocardial infarction. Seventy days after the start of cilostazol
      therapy, he developed dyspnea, dry cough, and fever. He was admitted to our
      hospital on April 13, 1923. Chest radiography and CT revealed a ground glass
      appearance. All drugs except isosorbide dinitrate were discontinued and he was
      treated with steroids under the presumptive diagnosis of drug-induced
      pneumonitis. Steroid therapy was effective. The result of a lymphocyte
      stimulation test was positive for cilostazol. Based on the above findings,
      cilostazol-induced pneumonitis was diagnosed. To our knowledge, there have been
      no previous reports of cilostazol-induced pneumonitis.

PMID- 7731121
TI  - [Pharmacokinetics of transbronchially injected flconazole in pulmonary
      aspergillosis].
AB  - A 68-year-old woman had a pulmonary aspergilloma in the left upper lobe, with old
      cavitary pulmonary tuberculosis. Surgery was not possible because of marginal
      ventilation, and the patient was treated by transbronchial injection of
      Fulconazole. After five injections of 50 mg of Fulconazole, the fungus ball had
      decreased in size. To study the pharmacokinetics of Fulconazole after
      transbronchial injection, its concentration in serum was measured. The values of
      serum Fulconazole concentration were 0.7 microgram/ml at 1 h, 0.8 microgram/ml at
      4 h, 0.8 microgram/ml at 8 h, 0.7 microgram/ml at 12 h, 0.7 microgram/ml at 24 h,
      and 0 microgram/ml at 48 h after transbronchial injection. These results indicate
      that Fulconazole was absorbed well. Furthermore, these values are equal to those
      obtained after intravenous administration of 50 mg and are higher than those
      obtained after intravenous administration of 25 mg. Fulconazole may have been
      absorbed via the bronchial epithelium, because of destruction of alveoli,
      connective tissue proliferation in the cavitary wall and secondary
      bronchiectasis.

PMID- 7731122
TI  - [Treatment of tuberculous tracheobronchial stenoses with expandable metallic
      stent (EMS)s placed during percutaneous cardiopulmonary support (PCPS)].
AB  - A 63-year-old woman was taken to a hospital by ambulance because of dyspnea. She
      was admitted in nearly complete cardiopulmonary arrest. CPR was started
      immediately, and the patient was mechanically ventilated via a tracheostomy tube.
      Abnormally high airway pressures 40-50 cmH2O were required during positive
      pressure ventilation. Saber-sheath like stenoses of the lower trachea 3 cm long
      and left main stem bronchus 2 cm long were found by bronchoscopy. It was
      difficult to pass a 3-mm-diameter bronchoscope through these stenoses. The right
      main stem bronchus was completely obstructed. A chest radiograph showed a
      completely collapsed right lung and a scarred upper lobe of the left lung,
      probably caused by previous tuberculosis. Weaning from the ventilator was
      attempted over three months. However, the patient could not breathe by herself
      because of airway obstruction. She was referred to our hospital for the placement
      of stents into the stenotic parts of the airways. A longitudinally connected
      Gianturcotype EMS, 15 mm in diameter and 50 mm long was placed in each area of
      stenosis under general anesthesia. During the placement of EMSs, PCPS was used
      for 113 minutes instead of mechanical ventilation of the lungs. Hemodynamics were
      stable during PCPS. A bypass flow of 2.0-2.8 l/min/m2 was used. Oxygen saturation
      of arterial blood taken from an earlobe was maintained at 100%. Blood taken from
      the left radial artery had a PaO2 of 269.4 mmHg and a PaCO2 of 40.2 mmHg. There
      were no complications after the procedure. One month later, the stenoses had
      become slightly dilated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731123
TI  - [Pulmonary actinomycosis presenting as a mass shadow with a cavity on chest
      radiography].
AB  - A 53-year-old woman was admitted with diabetes mellitus. After admission, a tumor
      shadow was detected by chest radiography and blood was found in her sputum.
      Despite further investigations, no definite diagnosis was made. Pulmonary wedge
      resection was performed because malignancy could not be excluded. Histological
      examination of the resected lung specimen led to the diagnosis of pulmonary
      actinomycosis. In Japan, 59 cases of pulmonary actinomycosis were reported
      between 1964 and 1993. These reports indicate that many cases of this disease are
      diagnosed by histological examination of resected lung specimens. Pulmonary
      actinomycosis has become even rarer recently because of the development of
      chemotherapy. We report this case and discuss the relevant literature.

PMID- 7731124
TI  - [A case of rheumatoid arthritis with a remarkable left-right difference in
      pulmonary lesions and acute exacerbation of pneumonia].
AB  - A 59-year-old woman had a four-year history of rheumatoid arthritis. Despite
      treatment with prednisolone for interstitial pneumonia, her chest X-ray films
      revealed gradual progression of reticular shadows, mainly in the left lung, and
      during the third hospitalization she died of respiratory failure due to acute
      exacerbation of pneumonia. At autopsy, there was a remarkable difference in lung
      weight: left 250 g, right 510 g. Microscopically, the pulmonary lesion was mild
      fibrosing interstitial pneumonia, with remarkable luminal organization and
      macrophages in parts. The features of unilateral interstitial pneumonia with
      bronchiolitis obliterans organizing pneumonia were clearer in the left lung. The
      cause of the acute exacerbation and of the difference in interstitial pneumonia
      between sides could not be identified.

PMID- 7731125
TI  - [A case of necrotizing sarcoid granulomatosis].
AB  - A 60-year-old woman was admitted to our hospital because of progressive cough and
      chest pain for 2 months. She also complained of exertional dyspnea. Bilateral
      diffuse infiltlative shadows were found on the chest roentogenogram. Ground-glass
      opacity in the middle lobe and lingula, and subpleural patchy consolidation were
      seen on the computed tomogram of the chest. Arterial oxygenation and diffusing
      capacity were low. The level of angiotensin-converting enzyme in serum was
      normal, but that of lysozyme was high. In the BAL (broncho-alveolar lavage)
      fluid, total cell count and the number of lymphocytes were high, and the CD 4/8
      ratio of the lymphocytes was high. Open lung biopsy revealed numerous confluent
      sarcoid granulomas with necrosis, which strongly correlated with severe
      vasculitis. After necrotizing sarcoid granulomatosis was diagnosed, prednisolone
      was administered, which resulted in improvement of symptoms and disappearance of
      chest-radiograph shadows. Necrotizing sarcoid granulomatosis may be seen as a
      variant type of sarcoidosis. However, clinical findings including the chest
      radiograph shadows and clinical course of this case differ from those of ordinary
      sarcoidosis. These clinical findings can be attributed to severe vasculitis, as
      revealed by histological examination.

PMID- 7731126
TI  - [A case of alveolar soft part sarcoma found by pulmonary metastasis].
AB  - A 34-year-old housewife presented to a hospital because of dry cough. Her chest
      radiograph showed bilateral multiple nodular lesions. Smaller but similar lesions
      had been seen on the chest radiograph 2 years earlier. Because the tissue taken
      during a trans bronchial biopsy was non-diagnostic, open lung biopsy was done and
      the diagnosis was pulmonary metastasis of alveolar soft part sarcoma. The primary
      tumor was found in her left calf by MRI. Malignant tumors are important for
      differential diagnosis of slow-growing multiple pulmonary nodules, and in some
      cases MRI is useful for finding the primary site.

PMID- 7731127
TI  - [A case in which bronchorrhea was alleviated by oral erythromycin and inhalation
      of beclomethasone and furosemide].
AB  - A 55-year-old woman with bronchorrhea and bronchial asthma was admitted to our
      hospital in June, 1992. On admission, she was producing a large volume of sputum
      (200 ml) each day. The volume decreased with oral administration of erythromycin
      and inhalation of beclomethasone. Next, inhalation of furosemide was added to the
      regimen, which lead to symptomatic improvement in mucus clearance, although the
      sputum increased in volume. The concentrations of albumin, fucose, sialic acid,
      and phosphatidylcholine in the sputum changed with these treatments, as did the
      lecithin/sphingomyelin ratio. These observations suggest that these drugs affect
      not only the quantity but also the quality of sputum.

PMID- 7731128
TI  - [Solitary rectal carcinoma metastasis to the left hilar lymph nodes: a case
      report].
AB  - A 66-year-old woman was referred to this institution for treatment of hemoptysis,
      atelectasis of the left upper lobe, and marked hypoxia necessitating oxygen
      therapy. A low anterior resection of the rectum had been performed for rectal
      adenocarcinoma 6 years and 3 months before this admission, and was followed by
      another resection after a local recurrence 20 months later. Bronchoscopy revealed
      an endobronchial tumor obstructing the left upper lobe bronchus. Tissue from a
      transbronchial biopsy revealed metastatic rectal carcinoma of the endobronchial
      lumen. There was no evidence of local recurrence or metastasis to other organs. A
      left pneumonectomy and lymph node dissection were performed successfully. The
      postoperative course was uneventful, and the patient was discharged after marked
      improvement of the arterial blood gas results. The pathological diagnosis of a
      resected tissue specimen was metastatic adenocarcinoma of the left hilar lymph
      nodes with invasion of the left main bronchus and protrusion into the
      endobronchial lumen. The patient remained disease-free for 6 months. At that
      time, computed tomography of the chest disclosed small metastases in the right
      lung and chemotherapy was begun.

PMID- 7731130
TI  - [A case of pulmonary alveolar proteinosis treated successfully with repeated
      bronchoalveolar lavage and surfactant replacement therapy].
AB  - A 24-year-old woman who had suffered from pulmonary alveolar proteinosis for
      eight years was admitted to Jichi Medical Hospital with severe pneumonia. She was
      mechanically ventilated, and her condition markedly improved after repeated
      bronchoalveolar lavage with surfactant replacement therapy. This method was used
      because she had been resistant to the conventional unilateral lung lavage method
      for 12 months. During the bronchoalveolar lavage procedure, she became
      progressively hypoxic, but recovered immediately after the instillation of
      surfactant. The combination of bronchoalveolar lavage with surfactant replacement
      via a fiberoptic bronchoscope may be useful in treating other patients with
      pulmonary alveolar proteinosis.

PMID- 7731129
TI  - [A case of hypersensitivity pneumonitis probably caused by a humidifier in
      winter].
AB  - A 64-year-old man was admitted complaining of cough, hemoptysis, dyspnea, and
      fever. His chest X-ray film on admission showed reticulo-granular shadows in both
      lung fields. Ausculation of his chest revealed fine crackles in both lower zones.
      After admission, he was treated with antibiotics, but his chest-radiographic
      appearance worsened temporarily, and sputum cytology results were repeatedly
      positive. Diagnosis was difficult. Differential cell count of the bronchoalveolar
      lavage fluid showed lymphocytosis, with a high CD 4/8 ratio. Transbronchial lung
      biopsy specimens revealed Masson bodies and alveolitis. With antibiotic therapy
      alone, his condition improved, and he was discharged. Five and a half hours
      later, his symptoms worsened and he was readmitted. His chest X-ray film on the
      second admission was almost the same as that on the first admission. His symptoms
      became less severe, and his condition improved without treatment.
      Hypersensitivity pneumonitis was diagnosed. Because the onset was in February,
      this was not considered to be a case of so-called summer type hypersensitivity
      pneumonitis a provocation test was done with water from the humidifier he had
      been using at home. The white blood cell count increased and PaO2 decreased
      significantly, so the result of the provocation test was thought to be positive.
      Therefore, so-called humidifier lung was strongly suspected. The results of
      sputum cytology on the first admission were probably falsely positive.

PMID- 7731131
TI  - [The effects of the treatment with oxitropium bromide after one month or more in
      patients with pulmonary emphysema--evaluation of pulmonary function tests,
      exercise tests, and a questionnaire].
AB  - Chronic effects of oxitropium bromide were studied in patients with pulmonary
      emphysema. Pulmonary function tests, an exercise test, and a questionnaire were
      used. Seven subjects underwent two successive studies, including a questionnaire
      on QOL, pulmonary function tests, and an exercise test before and after one month
      or more of regular inhalation of ocitropium bromide (600 micrograms/day). The
      complaint of breathlessness was significantly reduced and the ability to perform
      activities of daily living had improved slightly after the treatment. There were
      no significant differences in the values of arterial oxygen pressure at rest. The
      VC, RV/TLC, and peak expiratory flow rate improved. A significant decrease in
      oxygen uptake at rest, a slight decrease in minute ventilation at rest, and a
      significant prolongation of exercise time were observed after the treatment. No
      other changes were noted. We conclude that oxitropium bromide may improve lung
      mechanics and reduce the work of respiratory muscles.

PMID- 7731132
TI  - A family's experience with mental illness.

PMID- 7731133
TI  - The role of the family in the strengths model of psychiatric community case
      management.
AB  - The participation of the family in mental health care has undergone many changes
      through the years. The manner in which family resources are utilized within the
      framework of the strengths model of case management is reviewed. The utilization
      of this resource for both the well being and increased community tenure of the
      mental health care consumer is critical.

PMID- 7731134
TI  - Is beta 2-microglobulin a mediator of bone disease?

PMID- 7731135
TI  - Growth abnormalities in cultured mesangial cells from rats with spontaneous
      glomerulosclerosis.
AB  - Age-related glomerulosclerosis (GS) occurs in normotensive rats of the Milan
      strain (MNS), but not in genetically-matched hypertensive animals (MHS). Altered
      mesangial cell (MC) proliferation and matrix expansion are common features of the
      glomerular scarring process. We evaluated proliferation and matrix protein
      synthesis of cultured MC from MNS and MHS animals aged 1 and 8 months, that is,
      before and after the occurrence of GS. [3H]-thymidine (TdR) incorporation into
      DNA of MC from MNS rats stimulated by 10% FBS serum increased with donor aging
      from 115 +/- 6.0 to 176 +/- 15, P < 0.01 (% cpm/well over quiescent controls +/-
      SEM). Under the same experimental conditions, cell counts changed from 101 +/-
      4.0 to 146 +/- 5.0, P < 0.01 (% cells/well over quiescent controls).
      Additionally, cytosolic Ca2+ concentration ([Ca2+]i) rised from 115 +/- 19 to 220
      +/- 32 nM and from 112 +/- 24 to 734 +/- 136 nM when fura-2-loaded cells from
      young and old MNS rats, respectively, were stimulated with 1% FBS. The rate of
      collagen production also increased with donor age, as well as collagen IV and
      laminin B1 mRNA expression. In contrast, in MC from MHS rats both DNA synthesis
      and cell replication rate declined as function of donor age. No differences in
      the [Ca2+]i responses to FBS were observed, nor collagen production changed with
      MHS rat senescence. We conclude that the age-associated decline of proliferative
      activity in MC from MHS animals could actually reflect a normal process of cell
      aging, possibly protecting from the occurrence of GS.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7731136
TI  - Apoptosis in the repair process of experimental proliferative glomerulonephritis.
AB  - The recovery from the proliferative glomerulonephritis (GN) with reduction of
      hypercellularity is known in various experimental and human GN. To elucidate the
      participation of apoptosis in GN, we studied the experimental Thy-1.1 GN for six
      weeks. Apoptosis was recognized by both light and electron microscopy, and the
      biochemical expression of apoptosis was morphologically confirmed by in situ end
      labeling method of fragmented DNA, using terminal deoxy-transferase.
      Mesangioproliferative GN was induced by a single administration of anti-Thy-1.1
      monoclonal antibody in a rat. Mesangial cell proliferation started early in the
      process and the number of glomerular cells peaked from day 7 to day 10.
      Subsequently, the degree of proliferative lesion diminished with obvious
      reconstruction of the capillary structure, as well as decrease in the number of
      glomerular cells. During this period, proliferated mesangial cells returned to
      their original level of cellularity and apoptosis apparently increased in number
      among the glomeruli. Apoptosis was significantly noted from day 7 to week 4 and
      was in its maximum at day 10 to week 2. Following this period, by week 6 most of
      the glomeruli reverted to their original structure. The number of infiltrated
      neutrophils and macrophages in the glomeruli slowly decreased during the course
      of the disease, and a few apoptosis were also observed. It is concluded that
      proliferated glomerular cells regress by apoptosis in the repairing process of
      GN. Apoptosis plays an essential role in the recovery to the original glomerular
      structure in GN.

PMID- 7731137
TI  - Biphasic increase in circulating and renal TNF-alpha in MRL-lpr mice with
      differing regulatory mechanisms.
AB  - Tumor necrosis factor (TNF)-alpha contributes to expansion of lymphocytes in
      neonatal mice and can accelerate renal injury. T cells induced by the lpr gene
      promote renal injury. However, the lpr gene alone is insufficient to cause renal
      damage, since MRL-lpr, but not C3H-lpr mice develop lupus nephritis. In this
      study, we examined the temporal expression of TNF-alpha in the kidney and
      circulation of mice (MRL and C3H) with the lpr gene and their congenic
      counterparts (++). We measured a bioactive TNF-alpha using L929 cells and tissue
      expression with an avidin-biotin immunoperoxidase method. A biphasic increase in
      circulating TNF-alpha in MRL-lpr mice was detected. There was an initial peak in
      neonatal mice (703 +- 208 pg/ml) which normalized by two months of age (87 +- 13
      pg/ml) and reascended proportional to the severity of renal injury (non
      proteinuric 570 +/- 87, proteinuric; 1255 +/- 135 pg/ml). In addition, there was
      only a single peak in neonatal C3H-lpr mice (1270 +/- 318 pg/ml) with a nadir by
      six weeks of age (434 +/- 52 pg/ml). In contrast, serum TNF-alpha was low in MRL
      (++) and C3H-(++) mice (80 +/- 3 and 95 +/- 30 pg/ml), respectively. TNF-alpha
      expression in kidneys paralleled the serum pattern in MRL-lpr mice. Enhanced TNF
      alpha expression was restricted to tubular epithelial cells (TEC) in neonatal MRL
      lpr and C3H-lpr mice, and not detected in congenics. In adult mice, intrarenal
      TNF-alpha expression was more ubiquitous and was detected in glomeruli, vascular
      smooth muscle and perivascular infiltrating cells as well as TEC.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7731138
TI  - Internephron heterogeneity of growth factors and sclerosis--modulation of
      platelet-derived growth factor by angiotensin II.
AB  - We studied the early phase after 5/6 nephrectomy in Munich-Wistar rats to
      determine whether treatment with angiotensin II receptor antagonist (AIIRA)
      modulates the expression of platelet-derived growth factor (PDGF) mRNA and its
      protein among the glomeruli which are undergoing progressive hypertrophy and
      sclerosis. Average PDGF-B immunohistochemistry staining score (IHS, 0 to 3 scale)
      in glomeruli and PDGF-B chain mRNA from kidneys were both increased in 5/6
      nephrectomy rats (N = 6) versus age-matched normal (N = 5) at week 4, when
      glomeruli were at early stages of sclerosis (IHS, 0.81 +/- 0.12 vs. 0.19 +/-
      0.05; sclerosis index, S.I., 0 to 4 scale: 0.41 +/- 0.04 vs. 0.05 +/- 0.01, both
      P < 0.05). AIIRA (80 mg/liter drinking water, N = 6) started at time of 5/6
      nephrectomy prevented the development of sclerosis (S.I. 0.08 +/- 0.03) and
      decreased PDGF-B protein (IHS 0.22 +/- 0.08, both P = NS vs. normal), and PDGF-B
      chain mRNA. In contrast, triple therapy (TRX; hydralazine, reserpine and
      hydrochlorothiazide, N = 5) in doses which controlled systemic blood pressure
      resulted in intermediate level of glomerulosclerosis at this early time point of
      progressive injury. Concurrently, TRX failed to affect the expression of PDGF-B
      protein (IHS 0.86 +/- 0.19) or its mRNA expression. The PDGF-B distribution was
      not uniform amongst the glomeruli with varying stages of sclerosis. There was a
      strong correlation in individual glomeruli of increased PDGF-B staining with
      early sclerotic changes (P < 0.01), with the disappearance of this correlation in
      glomeruli with advanced sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731139
TI  - Developmental expression of renal angiotensin II receptor genes in the mouse.
AB  - The cellular distribution of angiotensin II type 1 (AT1) and type 2 (AT2)
      receptor mRNA was examined in mouse kidneys at several embryonic stages (12 to 18
      days; 19 days = full term) and up to three weeks after birth by in situ
      hybridization. The expression of both AT1 and AT2 mRNAs appeared simultaneously
      at 14 days of gestation. However, their distributions were contrasting: AT1 mRNA
      was expressed in mature glomeruli and maturing S-shaped bodies throughout the
      stages examined. AT1 expression was also detected at 16 days of gestation in the
      proximal and distal tubules and peaked at the end of gestation. Both the temporal
      and spatial expression of AT1 coincide with the differentiation and proliferation
      of glomerular mesangial and tubular cells during nephrogenesis. In contrast, AT2
      mRNA was present only in the mesenchymal cells adjacent to the stalk of the
      ureter bud at early developmental stages, and, later, extended to the mesenchymal
      cells located near, but outside, the nephrogenic area of superficial cortex and
      also the cells between collecting ducts. AT2 expression in these regions
      decreased markedly within three weeks after birth. Temporally and spatially, AT2
      mRNA expression coincides with the epithelial-mesenchymal interactions that take
      place during early phases of nephrogenesis. The site of AT2 expression also
      overlaps closely with that of a specific group of cells which undergo apoptosis
      following nephrogenesis. Thus, contrary to current belief, the activation of AT1
      and AT2 genes takes place in different cell types of the kidney during embryonic
      development, and thereby conceivably contributes to the ontogeny of those
      specific renal cells.

PMID- 7731140
TI  - Expression of type 1 plasminogen activator inhibitor in renal tissue in murine
      lupus nephritis.
AB  - Many renal diseases are associated with fibrin deposition in the glomeruli, a
      situation that reflects an abnormality in the balance between the coagulation and
      fibrinolytic systems. We recently demonstrated that normal mouse kidney contains
      very low levels of type 1 plasminogen activator inhibitor (PAI-1), a potent anti
      fibrinolytic protein, but that during endotoxemia, large amounts of PAI-1 protein
      and mRNA are expressed in glomerular and peritubular endothelial cells. These
      results raise the possibility that overexpression of PAI-1 in the glomerulus may
      contribute to the ongoing pathology seen in renal disease. To directly
      investigate this possibility, we studied PAI-1 expression in MRL/lpr mice, using
      in situ hybridization and immunohistochemistry. Female MRL/lpr mice develop early
      onset lupus glomerulonephritis (GN), a disease in which fibrin deposition is
      detected in the glomerulus and in which anti-coagulation therapy improves the
      prognosis. We detected very low levels of PAI-1 mRNA and antigen in the smooth
      muscle cells of renal vessels and in the renal papilla of 16 control mice. In
      contrast, PAI-1 was expressed in relatively high levels throughout the kidneys of
      33 out of 34 diseased mice, both within the glomerulus and also in tubules and
      vessels. Moreover, the level of PAI-1 in the tissues seemed to correlate with the
      severity of the disease. PAI-1 expression was localized to endothelial cells,
      parietal epithelial cells, tubular epithelial cells and infiltrating mononuclear
      cells in the tubulointerstitium. None of these cells express detectable levels of
      PAI-1 in the normal kidney. The inappropriate expression of PAI-1 in the kidneys
      of mice with lupus GN suggests that this important inhibitor of fibrinolysis may
      play a role in the pathogenesis of this disease process.

PMID- 7731141
TI  - Excess PTH in CRF induces pulmonary calcification, pulmonary hypertension and
      right ventricular hypertrophy.
AB  - Calcification of the lungs occurs in chronic renal failure (CRF) and may
      adversely affect both pulmonary and right ventricular function. The present study
      examined the role of excess parathyroid hormone (PTH) in the genesis of pulmonary
      calcifications in dogs with experimental CRF and evaluated calcium content of
      lungs, diffusing lung capacity (DCO), mean pulmonary artery pressure (MPAP),
      right ventricular pressure (RVP), and right ventricular hypertrophy (RVH) in six
      normal, six with CRF, and six thyroparathyroidectomized (CRF-PTX) dogs. CRF-PTX
      animals were maintained normocalcemic and euthyroid. The degree and duration of
      CRF were not different between the two groups with CRF. The mean value of the
      serum PTH in CRF dogs was 166 +/- 42 microliters Eq/ml, but was undetectable in
      CRF-PTX animals. Thallium scan provided evidence consistent with RVH in CRF dogs
      but not in CRF-PTX animals. Calcium content of lungs was markedly elevated in CRF
      dogs (7656 +/- 1657 mg/kg dry wt) but modestly increased in CRF-PTX (1057 +/- 117
      mg/kg dry wt) as compared to normal (673 +/- 34 mg/kg dry wt). RVP and MPAP were
      significantly (P < 0.01) higher and DCO significantly lower in CRF dogs than in
      normal or CRF-PTX animals. These parameters were not different in the latter two
      group of dogs. In three additional dogs with CRF of one year duration which were
      followed for an additional year after parathyroidectomy, these abnormalities were
      corrected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731142
TI  - Mechanisms of aluminum-induced microcytosis: lessons from accidental aluminum
      intoxication.
AB  - Twenty-three hemodialysis patients exposed to an accidental aluminum overload,
      showed increased erythropoietin requirements and decreased erythrocyte mean
      corpuscular volume (MCV). At the peak of the intoxication, MCV and plasma
      aluminum levels changed from unrelated (r = 0.02) to strongly related (r = 0.425)
      variables. The molar proportion of plasma aluminum to plasma iron increased
      dramatically (from 1:13.8 to 1:2.4). This significant increment in the
      aluminum/iron ratio made higher the relative offer of aluminum with respect to
      iron to the erythroid precursor cells. Accordingly, in a subset of 13 randomly
      selected aluminum-intoxicated patients we found increased intraerythrocytic
      aluminum, which paralleled the increase in plasma aluminum. Furthermore, in the
      aluminum-intoxicated group, intraerythrocytic ferritin, a marker of iron content,
      and the ratio between erythrocyte and plasma ferritin were lower (P < 0.01 and <
      0.001, respectively), than in the control group. These findings support the
      hypothesis that in some cases of aluminum-related microcytosis, a ferropenic
      mycrocitosis, as expression of erythroid ferropenia, may exist in spite of the
      presence of normal body iron stores.

PMID- 7731143
TI  - Vascular compliance in sodium-sensitive and sodium-resistant borderline
      hypertensive patients.
AB  - Recently, we demonstrated a reduction in the compliance of the carotid, femoral
      and brachial arteries in sodium-sensitive subjects who had consumed a regular
      sodium intake of approximately 120 mmol per day, as compared to both sodium
      resistant borderline hypertensive subjects and normotensive controls. Venous
      compliance was not different between the two borderline hypertensive groups and
      was only slightly lesser than in controls. Large artery compliance was studied
      using a non-invasive ultrasound vessel wall movement detector system, while
      venous compliance was determined by means of strain gauge plethysmography. The
      borderline hypertensive subjects were subsequently treated with enalapril 10
      mg/day, felodipine 5 mg/day or placebo during six months. Despite similar
      reductions in blood pressure, enalapril induced a significant increase of the
      muscular femoral and brachial artery compliance, but not of the elastic carotid
      artery, while felodipine did not influence large artery compliance at all in the
      sodium-sensitive group. The effect of enalapril on muscular artery compliance was
      established through a dose-dependent increase in distension and not through a
      change in arterial diameter. Arterial compliance was not influenced by either of
      the drugs in the resistant group. Venous compliance was also not altered by the
      medication. In conclusion, femoral and brachial artery compliance in sodium
      sensitive borderline hypertensive subjects, which was found to be lower than that
      of sodium-resistant subjects, improved with antihypertensive treatment with
      enalapril but not with felodipine, despite the similar reductions in blood
      pressure induced by both drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731144
TI  - Infiltration of the kidney by alpha beta and gamma delta T cells: effect on
      progression in IgA nephropathy.
AB  - We have studied renal biopsies from three groups of patients to determine if
      alpha beta T cells or gamma delta T cells are present, and whether their presence
      is correlated with disease progression in IgA nephropathy (IgAN). Group one
      comprised thin basement membrane disease biopsies (non-immunological control, N =
      7); group two were patients with IgAN and stable renal function one year
      following biopsy (stable, N = 7); and group three were IgAN patients with rapidly
      declining renal function after one year (progressive, N = 7). Immunohistochemical
      staining using monoclonal antibodies (CD3, TcR beta, TcR delta) and molecular
      studies utilizing polymerase chain reaction amplification of cDNA transcribed
      from biopsy RNA, with primers specific for either the alpha beta TcR or gamma
      delta TcR, were undertaken. On immunohistochemistry a significant increase in CD3
      + cells in progressive biopsies was seen (vs. control P = 0.002, vs. stable P =
      0.002). The progressive biopsies infiltrate consisted of both alpha beta TcR (vs.
      control P = 0.001, vs. stable P = 0.003) and gamma delta TcR cells (vs. control P
      = 0.01). The RNA study demonstrated an increase in TcR C alpha transcription in
      the progressive (vs. control P = 0.003) biopsies. Increased TcR C delta
      transcription was seen in the progressive group (vs. control P = 0.01, vs. stable
      P = 0.02). We confirm that the presence of lymphocytes in IgAN biopsies predicts
      progressive disease. While alpha beta T cells are found in both stable and
      progressive disease, the presence of gamma delta T cells is only associated with
      progressive IgAN.

PMID- 7731145
TI  - Clinical and echocardiographic disease in patients starting end-stage renal
      disease therapy.
AB  - End-stage renal disease (ESRD) patients have a high cardiovascular mortality
      rate. Precise estimates of the prevalence, risk factors and prognosis of
      different manifestations of cardiac disease are unavailable. In this study a
      prospective cohort of 433 ESRD patients was followed from the start of ESRD
      therapy for a mean of 41 months. Baseline clinical assessment and
      echocardiography were performed on all patients. The major outcome measure was
      death while on dialysis therapy. Clinical manifestations of cardiovascular
      disease were highly prevalent at the start of ESRD therapy: 14% had coronary
      artery disease, 19% angina pectoris, 31% cardiac failure, 7% dysrhythmia and 8%
      peripheral vascular disease. On echocardiography 15% had systolic dysfunction,
      32% left ventricular dilatation and 74% left ventricular hypertrophy. The overall
      median survival time was 50 months. Age, diabetes mellitus, cardiac failure,
      peripheral vascular disease and systolic dysfunction independently predicted
      death in all time frames. Coronary artery disease was associated with a worse
      prognosis in patients with cardiac failure at baseline. High left ventricular
      cavity volume and mass index were independently associated with death after two
      years. The independent associations of the different echocardiographic
      abnormalities were: systolic dysfunction-older age and coronary artery disease;
      left ventricular dilatation-male gender, anemia, hypocalcemia and
      hyperphosphatemia; left ventricular hypertrophy-older age, female gender, wide
      arterial pulse pressure, low blood urea and hypoalbuminemia. We conclude that
      clinical and echocardiographic cardiovascular disease are already present in a
      very high proportion of patients starting ESRD therapy and are independent
      mortality factors.

PMID- 7731146
TI  - Differences between anti-myeloperoxidase- and anti-proteinase 3-associated renal
      disease.
AB  - We performed a retrospective study of the clinical features, the pattern of the
      pre-treatment renal function loss, the renal morphology and the outcome in 92
      patients with anti-neutrophil cytoplasmic autoantibodies directed against
      proteinase 3 (aPR3; N = 46) or myeloperoxidase (aMPO; N = 46). Patients with aMPO
      had a higher median age than patients with a PR3 (63 and 56 years; P < 0.05). The
      mean (+/- SD) number of affected organs in the aPR3 group exceeded that of the
      aMPO group (3.9 +/- 1.4 and 2.2 +/- 1.1; P < 0.01). The prevalence of renal
      involvement did not differ between patients with aPR3 and aMPO (83% and 67%,
      respectively; NS). Pre-treatment renal function deteriorated significantly faster
      in aPR3- than in aMPO-associated renal disease. The kidney biopsies from patients
      with aPR3 showed a higher activity index (10.2 +/- 3.8 and 7.3 +/- 3.2; P < 0.03)
      and a lower chronicity index (4.5 +/- 2.6 and 7.0 +/- 3.1; P < 0.02) than
      biopsies from patients with aMPO. The kidney survival at two years was 73% in
      patients with aPR3- and 61% in patients with aMPO-associated renal disease (NS).
      We conclude that renal function generally deteriorates faster in aPR3- than in
      aMPO-associated renal disease. This goes together with more active renal lesions
      in patients with aPR3 and more chronic renal lesions in patients with aMPO.
      Despite these differences, there is no difference in outcomes between both
      antibody groups.

PMID- 7731147
TI  - Intravenous calcitriol normalizes insulin sensitivity in uremic patients.
AB  - Recent studies suggest that secondary hyperparathyroidism and/or vitamin D
      deficiency are responsible for the insulin resistance in chronic renal failure.
      We investigated the effect of a 12-week intravenous treatment with 1,25
      dihydroxycholecalciferol on glucose metabolism in 10 hemodialysis patients
      compared with 10 healthy control subjects by the frequently-sampled intravenous
      glucose tolerance test, analyzed with the minimal model technique. Compared to
      control subjects, the uremic patients featured elevated levels of parathyroid
      hormone (432 +/- 60 vs. 41 +/- 4 ng/liter, P < 0.001), insulin resistance
      (insulin sensitivity index, SI: 4.9 +/- 0.8 vs. 9.5 +/- 0.9 min-1/(microU/ml), P
      < 0.002), increased posthepatic insulin delivery (6.48 +/- 2.48 vs. 2.73 +/- 3.14
      nmol/liter in 4 hr, P < 0.001) and a reduced C-peptide fractional clearance
      (0.033 +/- 0.004 vs. 0.085 +/- 0.009 min-1, P < 0.0002). Following treatment with
      1,25 dihydroxycholecalciferol, the parathyroid hormone levels decreased
      significantly to 237 +/- 30 ng/liter (P < 0.05), the insulin sensitivity index
      (SI: 9.6 +/- 2.2, P < 0.05) reached a value similar to that of control subjects,
      and posthepatic insulin delivery decreased to 4.63 +/- 0.83 nmol/liter in 4 hr (P
      < 0.01), while all the other parameters remained unchanged. In summary, uremic
      patients with secondary hyperparathyroidism were found to be severely insulin
      resistant and hyperinsulinemic. Intravenous vitamin D treatment led to a
      significant reduction of parathyroid hormone levels and to a complete
      normalization of insulin sensitivity in the hemodialysis patients. Thus,
      intravenous 1,25 dihydroxycholecalciferol improves insulin resistance in uremic
      patients, acting per se or by reducing secondary hyperparathyroidism.

PMID- 7731148
TI  - Glomerulonephritis associated with MRSA infection: a possible role of bacterial
      superantigen.
AB  - We report 10 cases of glomerulonephritis following methicillin-resistant
      Staphylococcus aureus (MRSA) infection. The clinical features of this syndrome
      were an abrupt or insidious onset of rapidly progressive glomerulonephritis
      (RPGN) with nephrotic syndrome and occasionally purpura, following MRSA
      infection. The renal histologic findings showed a variety of types of
      proliferative glomerulonephritis with varying degrees of crescent formation;
      immunofluorescence revealed of glomerular deposition of IgA, IgG, and C3.
      Laboratory findings showed polyclonal increases of serum IgA and IgG, with high
      levels of circulating immune complexes (ICs). Increased numbers of DR+CD4+, and
      DR+CD8+T cells were observed in the peripheral circulation, with a high frequency
      of T cell receptor (TCR) V beta + cells. MRSA produced enterotoxins C and A and
      toxic shock syndrome toxin (TSST)-1, all of which are known to act as
      superantigens. From the above observations, we speculate that post-MRSA
      glomerulonephritis may be induced by superantigens causing production of high
      levels of cytokines, and polyclonal activation of IgG and IgA. The formation of
      ICs containing IgA and IgG in the circulation result in development of
      glomerulonephritis and vasculitis. Accordingly, microbial superantigens may play
      an important role in the pathogenesis of this unique syndrome of nephritis and
      vasculitis.

PMID- 7731149
TI  - Plasma potassium response to acute respiratory alkalosis.
AB  - Acute respiratory alkalosis (hyperventilation) occurs in clinical settings
      associated with electrolyte-induced complications such as cardiac arrhythmias
      (such as myocardial infarction, sepsis, hypoxemia, cocaine abuse). To evaluate
      the direction, magnitude and mechanisms of plasma potassium changes, acute
      respiratory alkalosis was induced by voluntary hyperventilation for 20 (18 and 36
      liter/min) and 35 minutes (18 liter/min). The plasma potassium response to acute
      respiratory alkalosis was compared to time control, isocapnic and
      isobicarbonatemic (hypocapnic) hyperventilation as well as beta- and alpha
      adrenergic receptor blockade by timolol and phentolamine. Hypocapnic
      hypobicarbonatemic hyperventilation (standard acute respiratory alkalosis) at 18
      or 36 liter/min (delta PCO2-16 and -22.5 mm Hg, respectively) resulted in
      significant increases in plasma potassium (ca + 0.3 mmol/liter) and catecholamine
      concentrations. During recovery (post-hyperventilation), a ventilation-rate
      dependent hypokalemic overshoot was observed. Alpha-adrenoreceptor blockade
      obliterated, and beta-adrenoreceptor blockade enhanced the hyperkalemic response.
      The hyperkalemic response was prevented under isocapnic and isobicarbonatemic
      hypocapnic hyperventilation. During these conditions, plasma catecholamine
      concentrations did not change. In conclusion, acute respiratory alkalosis results
      in a clinically significant increase in plasma potassium. The hyperkalemic
      response is mediated by enhanced alpha-adrenergic activity and counterregulated
      partly by beta-adrenergic stimulation. The increased catecholamine concentrations
      are accounted for by the decrease in plasma bicarbonate.

PMID- 7731150
TI  - Treatment of hepatitis B virus-associated membranous nephropathy with recombinant
      alpha-interferon.
AB  - An open, randomized trial study on the therapeutic effect of recombinant alpha
      interferon (IFN alpha) in 40 patients with hepatitis B virus membranous
      nephropathy (HBVMN) was conducted. All were pathologically proven to have HBVMN
      which showed no response to corticosteroid treatment represented by persistent
      heavy proteinuria. Both HBeAg and HBsAg were positive in all. Group 1 was
      composed of 20 patients who were treated with recombinant IFN alpha (5 subjects,
      body wt < 20 kg; 8 subjects, body weight > or = 20 kg) by subcutaneous (s.c.)
      injection three times a week for 12 months. In group 2 there were 20 patients who
      received supportive treatment only. At the end of the third month of treatment,
      all patients in Group 1 were free of proteinuria. In contrast, 10 patients (50%)
      in Group 2 had persistent heavy proteinuria and another 10 patients (50%) had
      light proteinuria with exacerbation during respiratory tract infection. At the
      end of the twelfth month, 8 patients (40%) in Group 2 still had persistent heavy
      proteinuria and 12 patients (60%) had light proteinuria with frequent relapses.
      Eight patients (40%) in Group 1 had HBeAg seroconversion between the fourth and
      sixth months and HBsAg seroconversion between the tenth and twelfth months. HBe
      seroconversion only [HBeAg (-)/HBsAg (+)] was found in four patients. Four
      patients had no change in HBV serological markers [HBeAg (+)/HBsAg (+)]. The
      remaining 4 patients had HBeAg (-)/HBeAb (+) HBsAg (-)/HBsAb (-) at the end of
      the twelfth month. In contrast, there was no seroconversion of HBeAg (+)/HBsAg
      (+) in Group 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731151
TI  - Effect of intensive treatment on diabetic nephropathy in patients with type I
      diabetes.
AB  - We evaluated the long-term effect of an intensive treatment of diabetic
      nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin
      injections to achieve a good metabolic control) on glomerular filtration rate
      (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean
      age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6
      females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin
      excretion rate > 30 micrograms/min were treated intensively for 36 months. This
      intensive treatment consisted of multiple insulin injections, antihypertensive
      therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal
      function was evaluated as GFR and AER. HbA1c mean value decreased significantly
      from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min
      1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208
      micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P <
      0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/-
      26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P <
      0.01). We obtained a rise of GFR and a reduction of proteinuria after three years
      of this treatment. We suggest that this intensive treatment in all patients with
      early stage diabetic nephropathy may be effective in slowing the progression to
      renal failure.

PMID- 7731152
TI  - Toward novel antirejection strategies: in vivo immunosuppressive properties of
      CTLA4Ig.
AB  - Allograft rejection is a process that depends on T cell receptor-ligand
      interaction and costimulatory signals generated when accessory molecules binds to
      their ligands, such as CD28 to the B7 molecules. We investigated the possibility
      that B7 blockade in vivo by the soluble CD28 receptor homolog CTLA4Ig modulates
      rejection process in a rat model of kidney allograft. Lewis rats orthotopically
      transplanted with MHC incompatible kidney from Brown-Norway rats were given an
      intraperitoneal injection of CTLA4Ig (0.2 or 0.5 mg/day) or a nonspecific
      immunoglobulin for seven days, starting the day of transplant. While control rats
      rejected the graft within 10 days, all animals given CTLA4Ig had a prolonged
      kidney allograft survival, independently from the dose of the fusion protein
      employed. Actually, at the dose of 0.2 mg/day kidney grafts survived 36 to 50
      days (median 44 days), while with the highest dose graft survival was 40 to 60
      days (median 50 days). In all CTLA4Ig-treated rats renal grafts were well
      functioning as documented by serum creatinine concentrations comparable to age-
      and sex-matched control rats 30 days after transplant. At this time in vitro
      mixed lymphocyte culture (MLR) experiments showed a significant reduction of
      proliferation of peripheral blood lymphocytes from CTLA4Ig-treated rats when
      challenged with BN but not third party Wistar Furth lymphocytes. We have also
      shown that combining a short course of CTLA4Ig (0.2 mg/day) with a dose of
      cyclosporine (CsA) low enough to fail to inhibit graft rejection allowed
      indefinite engraftment of kidney allograft without the need of continuous
      immunosuppression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731153
TI  - Mechanism of erythrocyte accumulation of methylation inhibitor S
      adenosylhomocysteine in uremia.
AB  - We have recently demonstrated that methyl esterification of erythrocyte membrane
      proteins, a reaction involved in recognition and repair of specifically damaged
      proteins, is impaired in uremia. This is accompanied by a significant increase in
      intracellular S-adenosylhomocysteine (AdoHcy), a potent inhibitor of
      methyltransferases. AdoHcy accumulation is normally prevented by its enzymatic
      hydrolysis to homocysteine (Hcy) and adenosine, a reversible reaction catalyzed
      by AdoHcy hydrolase. To assess the contribution that Hcy offers in the elevation
      of AdoHcy, we measured plasma and red blood cell Hcy, AdoHcy, adenosine, and S
      adenosylmethionine (AdoMet) intracellular concentrations, as well as RBC AdoHcy
      hydrolase specific activity, in standard hemodialysis patients and normal
      subjects. Plasma and red blood cell Hcy levels are significantly higher in the
      dialysis group, and are positively correlated to AdoHcy levels. Adenosine and
      AdoMet levels, and AdoHcy hydrolase specific activity are not significantly
      different between the two groups. The enzymatic formation of labeled AdoHcy from
      Hcy and tracer adenosine appears to be significantly increased, in vitro, in
      erythrocytes from both control and uremic patients, when 50 microM Hcy
      (concentration comparable to plasma levels actually found in vivo in uremic
      patients) is added to the incubation medium. When erythrocytes from uremic
      patients are incubated in vitro in absence of Hcy, a significant reduction of
      intracellular AdoHcy is observed with time compared to identical samples
      incubated in presence of 50 microM Hcy, with a T1/2 of approximately 270 minutes.
      The results allow us to conclude that plasma and red cell Hcy levels actually
      found in uremia can be effectively responsible for the intracellular accumulation
      of the toxic compound AdoHcy.

PMID- 7731154
TI  - Induction of nodular sclerosis by insulin in rat mesangial cells in vitro:
      studies of collagen.
AB  - These studies evaluated the contribution of insulin to the development of the
      abnormal mesangial matrix that characterizes diabetic nephropathy and is common
      to mesangial cells in culture. Glomeruli were isolated from a single rat and
      divided into two aliquots. In one set (SI-MC), the insulin contained in the
      medium was only that contributed by the fetal calf serum (20%). For the other
      set, the tissue culture medium was supplemented with 1 microM insulin (SI+MC).
      Mesangial cell outgrowths from each condition were isolated, cloned, and
      propagated. At passage 4, mesangial cells were characterized by morphology and
      cell markers, and compared in terms of composition and appearance of the secreted
      extracellular matrix. SI-MC grew in nests of cells surrounded by a thin layer of
      matrix that was rich in collagen IV. In contrast, mesangial cells supplemented
      with insulin aggregated into macroscopic "hillocks" rich in collagens I and III
      as described previously. Insulin (1 microM) or IGF-I (0.1 microM) was
      subsequently added to the medium of SI-MC. Insulin, but not IGF-I, induced a
      change in culture morphology and collagen accumulation characteristic of SI+MC.
      In contrast to SI+MC, SI-MC express insulin receptors and at physiologic
      concentrations insulin is a more potent stimulator of MC proliferation than is
      IGF-I. Insulin-induced changes in the collagenous composition of the accumulated
      ECM were directionally correlated with the rate of collagen I synthesis measured
      by biosynthetic labeling experiments and collagens III and IV as determined by
      ELISA. These data demonstrate that insulin alters the phenotype of mesangial
      cells in culture and their expression of interstitial and basement membrane
      collagens. These observations implicate insulin as a factor in the pathogenesis
      of mesangial matrix accumulation in diabetic nephropathy. Furthermore, a method
      for culturing mesangial cells that accumulate an extracellular matrix that is
      similar in composition to normal mesangial matrix provides a new model system for
      future studies of mesangial cell biology.

PMID- 7731155
TI  - Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: a
      randomized trial. The Iohexol Cooperative Study.
AB  - The incidence of nephrotoxicity occurring with the nonionic contrast agent,
      iohexol, and the ionic contrast agent, meglumine/sodium diatrizoate, was compared
      in 1196 patients undergoing cardiac angiography in a prospective, randomized,
      double-blind multicenter trial. Patients were stratified into four groups: renal
      insufficiency (RI), diabetes mellitus (DM) both absent (N = 364); RI absent, DM
      present (N = 318); RI present, DM absent (N = 298); and RI and DM both present (N
      = 216). Serum creatinine levels were measured at -18 to 24, 0, and 24, 48, and 72
      hours following contrast administration. Prophylactic hydration was administered
      pre- and post-angiography. Acute nephrotoxicity (increase in serum creatinine of
      > or = 1 mg/dl 48 to 72 hours post-contrast) was observed in 42 (7%) patients
      receiving diatrizoate compared to 19 (3%) patients receiving iohexol, P < 0.002.
      Differences in nephrotoxicity between the two contrast groups were confined to
      patients with RI alone or combined with DM. In a multivariate analysis, baseline
      serum creatinine, male gender, DM, volume of contrast agent, and RI were
      independently related to the risk of nephrotoxicity. Patients with RI receiving
      diatrizoate were 3.3 times as likely to develop acute nephrotoxicity compared to
      those receiving iohexol. Clinically severe adverse renal events were uncommon (N
      = 15) and did not differ in incidence between contrast groups (iohexol N = 6;
      diatrizoate N = 9). In conclusion, in patients undergoing cardiac angiography,
      only those with pre-existing RI alone or combined with DM are at higher risk for
      acute contrast nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731156
TI  - Glycine-induced hyponatremia in the rat: a model of post-prostatectomy syndrome.
AB  - Post-prostatectomy syndrome (PPS) is characterized by hyponatremia after
      absorption of glycine irrigant. To study the pathogenesis of this syndrome, adult
      male rats with ligated ureters were infused over 15 minutes with 7.5 ml/100 g
      body weight of isosmotic glycine (N = 9) or mannitol (N = 9) and were compared to
      non-infused, ureter-ligated controls (N = 9). Immediately post-infusion, plasma
      sodium had decreased similarly in glycine- and mannitol-infused animals (111 +/-
      2 vs. 106 +/- 1 mmol/liter), but plasma osmolality remained at control levels in
      both groups (285 +/- 1 vs. 288 +/- 1 mOsm/kg). Two hours post-infusion,
      hyponatremia was stable in the mannitol group (108 +/- 1 mmol/liter), but in the
      glycine group plasma sodium increased significantly (to 120 +/- 1 mmol/liter).
      Plasma osmolality two hours post-infusion was maintained in both the glycine (287
      +/- 2) and mannitol (292 +/- 2) groups. Brain water in glycine-infused animals
      (3.90 +/- 0.01 liter/kg dry wt) was not significantly different from the mannitol
      infused group (3.85 +/- 0.01) and only 1.8% higher than non-infused controls
      (3.83 +/- 0.02). Brain tissue glycine did not differ between the three groups. In
      contrast, muscle water two hours post-infusion in the glycine group was 6% higher
      than mannitol-infused and 13% higher than non-infused animals. Muscle glycine
      content in the glycine group (67 +/- 4 mM/kg dry tissue) was increased when
      compared to both mannitol-infused (25 +/- 1) and non-infused (20 +/- 1)
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731157
TI  - Acid-base balance in chronic peritoneal dialysis patients.
AB  - Endogenous acid production has never been measured directly in dialysis patients
      and an empiric formula is used to estimate acid production from their protein
      catabolic rate. We have studied acid-base balance in 19 stable CAPD patients
      attending the peritoneal dialysis clinic of Mount Sinai Hospital. They obtained a
      24 hour collection of peritoneal dialysis fluid and urine while consuming their
      usual diet and performing their usual activities. Total alkali gain was
      calculated from net GI alkali absorption plus urinary net acid excretion plus
      alkali gain from dialysate, while total acid production was measured directly
      from the urinary and dialysate excretions of sulfate and organic anions. Net GI
      alkali absorption was estimated from the difference between cations (Na + K+Ca +
      Mg) and anions (Cl + 1.8P) in the 24 hour dialysate and urine collections minus
      the daily total amount of lactate infused. All of our patients had a normal or
      high serum bicarbonate concentration, which was stable with time. Total alkali
      gain was virtually identical to total acid production (54.2 vs. 52.4 mEq/day)
      which suggests that these patients were in neutral acid-base balance. Net GI
      alkali absorption (22.7 mEq/day) was one of the same range as that of chronic
      renal failure patients not on dialysis and represented almost one half of the
      total daily alkali gain. The daily acid production of 52.4 mEq/day was
      numerically equal to 84% of the protein catabolic rate expressed as g/day, which
      is similar to the predicted value of 77% of PCR reported in the
      literature.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731158
TI  - Efficacy of intrarenal ACE-inhibition estimated from the renal response to
      angiotensin I and II in humans.
AB  - Recent studies on the nature of the renin-angiotensin system (RAS) in animals
      have led to the concept that systemic and intrarenal RAS can be influenced to
      different degrees by angiotensin converting enzyme (ACE) inhibitors. Assessment
      of efficacy of intrarenal ACE inhibition by ACE inhibitors in humans is
      necessarily indirect and has not been reported. We therefore monitored the renal
      response to acute angiotensin (Ang) I infusion in volunteers taking 20 mg
      enalapril twice daily, and related the responses to the obtained increments in
      plasma Ang II levels. Ang I infusion rates of 4, 8, 16, and 32 pmol/kg/min caused
      gradual increments in plasma Ang I (maximal change from 26 +/- 18 to 578 +/- 120
      pmol/liter, P < 0.05) and, despite treatment with enalapril, also of Ang II (from
      3 +/- 1 to 29 +/- 5 pmol/liter, P < 0.05). This was associated with large
      reductions in renal plasma flow (paraaminohippurate clearance), filtration
      fraction, maximal urine flow, sodium excretion, lithium and uric acid clearance,
      and increments in mean arterial pressure and plasma aldosterone (P < 0.05 for
      each variable). Strong correlations existed between the changes in either
      variable and the increment in plasma Ang II. Infusions of Ang II at 1 and 4
      pmol/kg/min in the same subjects caused comparable increments in plasma Ang II
      and had similar physiological effects as found during the Ang I infusion.
      Analysis of covariance of the changes in plasma Ang II and each of the measured
      variables revealed no differences between Ang I and Ang II infusions.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7731159
TI  - Effect of lactate-buffered peritoneal dialysis fluids on human peritoneal
      mesothelial cell interleukin-6 and prostaglandin synthesis.
AB  - The present study focused on the evaluation of constitutive and cytokine
      stimulated human peritoneal mesothelial cell (HPMC) IL-6 and 6-keto-PGF1 alpha
      release following pre-exposure to peritoneal dialysis fluid (PDF). Exposure of
      HPMC to PDF pH 5.2 resulted in a time-dependent increase in cell cytotoxicity [as
      assessed by lactate dehydrogenase (LDH) release] and concomitant inhibition of
      constitutive and IL-1 beta stimulated IL-6 and 6-keto-PGF1 alpha synthesis. After
      15 minutes of exposure to PDF constitutive and IL-1 beta stimulated IL-6 release
      were reduced by 32.0 +/- 9.7% and 76.0 +/- 7.4% (N = 6, P < 0.046 and P < 0.027,
      respectively). PCR amplification of reverse transcribed mRNA from HPMC pre
      exposed to PDF pH 5.2 demonstrated suppression of IL-1 beta stimulated IL-6 and
      cyclooxygenase (Cox-1 and Cox-2) transcripts. In order to mimic the dialysis
      cycle in vivo, an in vitro dialysis system was established. HPMC were exposed
      first to control medium, PDF pH 5.2 or PDF 7.3 for 15 minutes and then
      sequentially to pooled spent peritoneal dialysis effluent for up to four hours.
      The cells were subsequently allowed to recover in control medium for 12 hours in
      the presence or absence of IL-1 beta or TNF-alpha (both at 1000 pg/ml). There was
      no evidence of significant cell toxicity as assessed by LDH release during either
      the 'in vitro dialysis' or 'recovery' phases. Under these conditions short term
      exposure to PDF pH 5.2 followed by 'in vitro dialysis' resulted in significant
      inhibition of cytokine stimulated IL-6 (69.6 +/- 18.2 vs. 96.7 +/- 27.9
      pg/microgram, N = 13; P < 0.020 for IL-1 beta) and 6-keto-PGF1 alpha (197.5 +/-
      89.2 vs. 289.6 +/- 114.5 pg/microgram, N = 13; P < 0.020 for IL-1 beta) and 6
      keto-PGF1 alpha (197.5 +/- 89.2 vs. 289.6 +/- 114.5 pg/microgram, N = 13; P <
      0.003) release when compared to cells incubated in control medium. Adjustment of
      the pH of PDF to 7.3 reversed its inhibitory effects. We conclude that short-term
      exposure to PDF pH 5.2 significantly inhibits HPMC cytokine and prostaglandin
      release, an effect which appears to be related to its initial pH. Repeated
      exposure to nonphysiological PDF might impair mesothelial cell function and thus
      modulate intraperitoneal inflammatory processes.

PMID- 7731160
TI  - Distribution of MHC class II alleles in primary systemic vasculitis.
AB  - Previous studies have shown a number of different associations between major
      histocompatibility complex (MHC) alleles and primary systemic vasculitis. Disease
      heterogeneity and the lack of specificity of certain MHC typing techniques may
      have contributed to the lack of consistency in those studies. We therefore
      studied a relatively homogeneous group of 94 patients with Wegener's
      granulomatosis, microscopic polyangiitis, or renal-limited vasculitis using
      molecular techniques that allow more precise assignment of MHC genotype. DNA was
      prepared from peripheral blood and DRB1 genotype determined by Taq restriction
      fragment length polymorphism. DQB1 and DPB1 genotype were assigned by polymerase
      chain reaction amplification followed by probing with allele-specific
      oligonucleotides. Specificity of associated anti-neutrophil cytoplasm antibodies
      (ANCA) was determined where possible by solid phase immunoassays using purified
      proteinase 3 (PR3) and myeloperoxidase (MPO). After correction for multiple
      comparisons there were no significant differences in the distribution of DRB1,
      DQB1 and DPB1 alleles between a local control group (N = 90 for DRB1, N = 50 for
      DQB1 and DPB1) and the patient group as a whole (N = 94) or two a priori defined
      subgroups (anti-PR3 positive, N = 35; anti-MPO positive, N = 22). We have
      therefore found no significant association between primary systemic vasculitis
      and any MHC class II allele. This, together with the fact that previous smaller
      studies have shown no consistent association, suggests that any such association
      is very weak, if it exists at all.

PMID- 7731161
TI  - Growth of cultured rabbit renal tubular cells does not require exogenous
      glutamine.

PMID- 7731162
TI  - Simultaneous isolation and biochemical characterization of connecting and
      collecting tubules by ficoll gradient.

PMID- 7731163
TI  - Serum cystatin C measured by automated immunoassay: a more sensitive marker of
      changes in GFR than serum creatinine.
AB  - Serum cystatin C has been suggested as a new marker of GFR. For the introduction
      of this marker into clinical use a rapid and automated method is required. We
      have developed and validated an assay for serum cystatin C using latex particle
      enhanced immunoturbidimetry. Intra- and inter-assay precision were < 3% and < 5%
      across the assay range. Analytical recovery was 93 +/- 3.8% and no lack of
      parallelism was demonstrated. Regression analysis of a method comparison with an
      enzyme-enhanced radial-immunodiffusion method, gave PETIA = 0.074 + 0.93 x SRID,
      r = 0.98, N = 100. Inter-assay precision profiles showed cystatin C was measured
      with two-fold better precision than creatinine on the same analyzer. Cystatin C
      measurement was neither interfered with by icterus nor by hemolysis. 1/cystatin C
      versus 1/creatinine concentrations gave r = 0.67, N = 469. Comparison of Cr EDTA
      GFR with 1/cystatin C and 1/creatinine gave r = 0.81 and 0.50, respectively, N =
      206. Calculating diagnostic sensitivity for abnormal GFR showed cystatin C to be
      significantly (P < 0.05) more sensitive than creatinine (71.4 vs. 52.4%).
      Cystatin C measurement using PETIA technology can be automated on the same
      instruments used routinely for the measurement of creatinine and offers better
      analytical performance and probably improved clinical sensitivity as a screening
      test for early renal damage.

PMID- 7731164
TI  - Accuracy of the urea reduction ratio in predicting dialysis delivery.

PMID- 7731165
TI  - Highly efficient adenovirus-mediated gene transfer into renal cells in culture.
AB  - In summary, we have shown that adenovirus vector efficiently introduced foreign
      gene into cultured renal cells both of mesangial and tubular origin. Genes
      transferred were properly expressed to produce the molecules of expected
      function. It was possible to introduce the gene into nearly 100% of the cells
      treated. Expression of the gene began as early as 12 hours after the infection,
      increased until 48 hours and persisted at least up to eight days. Finally, the
      vector was non-toxic to the cells, as judged from simple toxicity tests.
      Successful application of adenovirus vector enables for us to study function of
      pertinent molecules in suitable host cells and opens a new way for examining
      renal cellular physiology and pathophysiology.

PMID- 7731166
TI  - A nonsense mutation in the COL4A5 collagen gene in a family with X-linked
      juvenile Alport syndrome.
AB  - The X-linked form of Alport syndrome is associated with mutations in the COL4A5
      gene encoding the alpha 5-chain of type IV collagen. By using PCR-amplification
      and direct sequencing we identified a novel mutation involving a deletion of the
      last two bases in the codon GGA for Glycine-1479 in exon 47 of the COL4A5 gene in
      a patient with a juvenile form of X-linked Alport syndrome with deafness. This
      two base deletion caused a shift in the reading frame and introduced a premature
      stop codon which resulted in an alpha 5(IV)-chain shortened by 202 residues and
      lacking almost the entire NC1 domain. The mutation was found to co-segregate with
      the disease in the family. The information of the sequence variation in this
      family was used to perform carrier detection and prenatal diagnosis by allele
      specific oligonucleotide hybridization analysis and direct sequencing of PCR
      amplified exon 47. Prenatal diagnosis on chorionic villi tissue, obtained from
      one of the female carriers in the family, revealed a male fetus hemizygous for
      the mutated allele. A subsequent prenatal test in her next pregnancy revealed a
      normal male fetus. Prenatal diagnosis of Alport syndrome has not previously been
      reported.

PMID- 7731167
TI  - Renal acid-base transport: the regulatory role of the inner medullary collecting
      duct.

PMID- 7731168
TI  - Role of protein kinase C on the acute desensitization of renal cortical adenylate
      cyclase to parathyroid hormone.
AB  - The mechanisms of adenylate cyclase desensitization to parathyroid hormone are
      still unclear. Current evidence suggest that the signal generated after PTH
      binding to receptors results in activation of adenylate cyclase and stimulation
      of phospholipase C with subsequent activation of protein kinase C. Recent studies
      have suggested a role of protein kinase C on the regulation of the PTH-dependent
      receptor-adenylate cyclase system in cultured cells. Therefore, the present
      studies were conducted to examine the role of protein kinase C on the
      desensitization of canine renal cortical adenylate cyclase after an acute
      exposure in vivo to PTH. A group of normal dogs were treated with a single
      intravenous injection of 1 microgram/k of syn bPTH (1-34) or Nle bPTH (3-34). Ten
      minutes later, animals were subjected to bilateral nephrectomy and the kidney
      cortex processed for preparations of basolateral membranes for determinations of
      adenylate cyclase activity, as well as membrane and cytosolic fractions for
      analysis of protein kinase C activity. Animals not treated with PTH were used as
      controls. PTH administration in vivo resulted in a 46.9 +/- 9.3% decrease in
      maximal adenylate cyclase activity in vitro in response to syn bPTH (1-34) (P <
      0.001). Likewise, PTH binding as measured with 125I-Nle8,18,Tyr34-bPTH (1-34)NH2
      showed a 40 +/- 3% decrease. This alterations were associated with a marked
      translocation of protein kinase C from the cytosol to the membrane. Thus, protein
      kinase C activity in membrane fractions increased from 160.6 +/- 44.8 pmol Pi/min
      in controls to 500.4 +/- 123 in PTH treated dogs (P < 0.03).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7731169
TI  - Oxidized LDL and lipoprotein(a) stimulate renin release of juxtaglomerular cells.
AB  - Atherogenic lipoproteins accumulate in the arterial wall and may potentially
      stimulate neighboring cells. In the glomerulus the vascular pole resembles
      afferent arteries in close vicinity to the juxtaglomerular apparatus. We examined
      the effects of native and oxidized LDL and lipoprotein(a) [Lp(a)] on renin
      release of juxtaglomerular cells (JG cells) prepared in primary culture from
      mouse kidneys. Renin activity of JG cells was measured in culture supernatants
      and cells between the 20th and 40th hour of culturing. Spontaneous renin release
      into the cell supernatant was 26 +/- 1% of total activity. Control stimulation of
      JG cells by melittin or forskolin dose-dependently increased renin release up to
      90 +/- 2%. Incubation of JG cells with native LDL (50 and 300 micrograms/ml) or
      native Lp(a) (30 micrograms/ml) did not alter renin release. Oxidized LDL
      increased renin release to 34 +/- 1% and 43 +/- 1% at 50 and 300 micrograms/ml,
      while oxidized Lp(a) stimulated renin release to 33 +/- 1%, 42 +/- 1%, and 71 +/-
      2% at 1, 10, and 30 micrograms/ml, respectively. Coincubation with superoxide
      dismutase and catalase, enzymes removing O2- and H2O2, completely eliminated
      oxidized LDL and Lp(a)-stimulated renin release. In the absence of lipoproteins,
      renin release was significantly stimulated by activation of O2- formation by the
      xanthine/xanthine oxidase reaction. These data indicate that oxidized LDL and
      Lp(a) stimulate renin release in JG cells by a mechanism involving oxygen-derived
      radicals. Thus, oxidatively modified atherogenic lipoproteins may contribute to
      renin-dependent hypertension in renoparenchymatous kidney disease.

PMID- 7731170
TI  - Endothelin-1 induction of cyclooxygenase-2 expression in rat mesangial cells.
AB  - Prostaglandin E2 (PGE2) may be an important negative feedback modulator of
      endothelin-1 (ET-1)-stimulated mesangial cell proliferation and contraction.
      Recent studies suggest that ET-1 may induce prolonged mesangial cell PGE2
      production, however the mechanism of this effect is unknown. The current study
      was undertaken, therefore, to examine the long-term effect of ET-1 on mesangial
      cell PGE2 synthesis. ET-1 markedly increased PGE2 release by rat mesangial cells
      for at least six hours. Cyclooxygenase (COX) activity was increased by one hour
      and persisted for at least six hours. ET-1 increased COX-2, but not COX-1,
      protein and mRNA levels. Actinomycin D reduced ET-1-stimulated PGE2 synthesis and
      COX-2 mRNA expression, while cycloheximide superinduced COX-2 mRNA. Dexamethasone
      decreased ET-1-stimulated PGE2 release and COX-2 protein and mRNA levels. ET-1
      stimulated PGE2 release was prevented by BQ-123, an endothelin receptor A
      antagonist. We conclude that ET-1, via activation of the endothelin A receptor,
      causes a prolonged increase in mesangial cell PGE2 production that is partially
      dependent on induction of dexamethasone-inhibitable COX-2.

PMID- 7731171
TI  - Modulation of experimental mesangial proliferative nephritis by interferon-gamma.
AB  - The observation that interferon-gamma (IFN-gamma) inhibits cell proliferation and
      collagen synthesis of a variety of cell types in culture has suggested that IFN
      gamma may be useful in the treatment of fibroproliferative diseases. We
      administered recombinant IFN-gamma subcutaneously (10(5) U/kg/day for 3 days) to
      rats, beginning one day after the induction of mesangial proliferative nephritis
      with anti-Thy 1 antibody. IFN-gamma reduced glomerular (primarily mesangial) cell
      proliferation by 44% at days 2 and 4 compared to vehicle injected control rats
      with anti-Thy 1 nephritis (that is, proliferating cells that excluded the
      macrophage marker, ED-1, P < 0.001). Despite the inhibition of mesangial cell
      proliferation, IFN-gamma did not reduce the overall extracellular matrix
      deposition (by silver stain) or deposition of type IV collagen or laminin (by
      immunostaining) at 4 or 7 days, and glomerular type IV collagen and laminin mRNA
      levels were increased (1.4 and 1.7-fold) at 4 days relative to controls. The
      inability of IFN-gamma treatment to reduce mesangial matrix expansion may relate
      to the fact that IFN-gamma treated rats had a twofold increase in glomerular
      macrophages (that is, ED-1 positive cells, P < 0.001 at 2 and 4 days) with an
      increase in oxidant producing cells (day 2, P < 0.05) and a 1.6-fold increase in
      glomerular TGF-beta mRNA expression (4 days). This suggests that the effect of
      IFN-gamma to inhibit mesangial cell proliferation in glomerulonephritis may be
      offset by the ability of IFN-gamma to increase glomerular macrophages and TGF
      beta expression. These data also show that IFN-gamma can partly dissociate the
      mesangial proliferative response from the extracellular matrix expansion in
      glomerulonephritis.

PMID- 7731172
TI  - Adaptation of the kidney to protein intake and to urine concentrating activity:
      similar consequences in health and CRF.

PMID- 7731173
TI  - Expression of granzyme A and B proteins by cytotoxic lymphocytes involved in
      acute renal allograft rejection.
AB  - Granzymes A and B are serine-proteinases stored in the granules of activated
      cytotoxic T-lymphocytes and natural killer (NK) cells. Expression of granzymes in
      tissues can be used as an activation marker for cytotoxic cells. Using mAbs
      specific for human granzyme A or B in immunohistochemical staining techniques we
      investigated expression of granzyme A and B by lymphocytes infiltrating acutely
      rejected renal allografts. Twelve core needle biopsies were taken from ten
      different patients during an episode of acute rejection. Eleven biopsies
      contained high numbers of granzyme A and B positive lymphocytes infiltrating
      tubular epithelium, and vascular and glomerular structures. In one patient
      infiltrating lymphocytes did not express granzyme A and only low amounts of
      granzyme B. No correlation was found between the number of granzyme positive
      cells and the severity of the rejection as classified by conventional
      histological criteria. In one tissue specimen from a patient with a renal
      allograft without signs of rejection, the number of granzyme positive cells was
      much lower compared to that of the transplant group. In spite of the presence of
      a marked inflammatory infiltrate, no granzyme positive cells were detected in
      renal biopsies from patients with various inflammatory, not transplant-related,
      renal diseases. Phenotypic analysis showed that granzymes A and B were expressed
      by CD56+ NK cells and CD3+ cells, representing cytotoxic T-lymphocytes. Thus,
      this study demonstrates that granzyme A and B protein-expressing lymphocytes
      infiltrate the kidney allografts during an acute cellular rejection but not in
      several other inflammatory renal diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731174
TI  - Na+/H+ antiporter (NHE-1 isoform) in cultured vascular smooth muscle from the
      spontaneously hypertensive rat.
AB  - An increase in Na+/H+ antiporter activity may be involved in hyperproliferation
      of vascular smooth muscle cells (VSMC) and possibly in the vascular hyperplasia
      characteristic of hypertension. The present study was designed to examine cell
      proliferation, Na+/H+ exchange activity, and mRNA levels of the NHE-1 isoform of
      the Na+/H+ antiporter in cultured aortic VSMC derived from the spontaneously
      hypertensive rat (SHR) and from normotensive controls, the Wistar/Kyoto rat
      (WKY). VSMC derived from the SHR grown in early (2 to 6), but not in later (7 to
      10) sub-passages, exhibited an increase in [3H]-thymidine incorporation and
      shorter doubling times as compared to those derived from WKY rats. Na+/H+
      exchange activity assayed in the nominal absence of HCO3-/CO2, as the rate of
      intracellular pH (pHi) recovery after cell acidification was significantly higher
      in cells from SHR than in those from WKY rats when cells were studied in early
      sub-passages, but not in cells studied in later sub-passages. In cells grown in
      early sub-passage, Na+/H+ exchange activity assessed as the initial rate of Na+i
      accumulation following acute cell acidification was also significantly higher in
      SHR than WKY cells both in the nominal absence (10.22 +/- 1.15 and 6.98 +/- 1.17
      mmol Na+i/90 seconds, P < 0.05, respectively) and in the presence of HCO3-/CO2
      (9.94 +/- 1.02 and 5.59 +/- 0.86 mmol Na+/90 seconds, P < 0.01, respectively).
      There were no detectable differences in the level of steady-state Na+/H+
      antiporter (NHE-1) mRNA between VSMC from SHR and WKY rats. Our findings indicate
      that Na+/H+ exchange activity is increased in cultured aortic VSMC derived from
      SHR as compared to those derived from WKY rats. The higher functional activity of
      the Na+/H+ antiporter in VSMC from the SHR is due to a post-transcriptional
      event(s) and may be related to enhanced growth in culture.

PMID- 7731176
TI  - [Violent situations in nursing: when the pot overflows].

PMID- 7731175
TI  - Hormonal regulation of glutamine metabolism by OK cells.
AB  - The precise mechanism(s) of action of PTH, insulin or glucagon in the regulation
      of renal glutamine and ammonia metabolism is unknown. Our aim was to delineate
      the effects and the site(s) of action of these hormones on renal glutamine
      metabolism. Experiments were carried out using OK cells as a model system. Cell
      cultures were incubated for three hours in a bicarbonate buffer of pH 7.4
      supplemented with either 1 mM [2-15N] or [5-15N] glutamine and 10(-7) M PTH,
      insulin or glucagon. Comparative studies were performed at pH 6.8, 7.4 or 7.6
      without hormone. PTH and acute acidosis significantly stimulated glutamine
      metabolism via both the phosphate-dependent glutaminase (PDG) and glutamate
      dehydrogenase (GLDH) pathways. The opposite was observed at pH 7.6. Insulin
      augmented flux via PDG with little effect on the GLDH pathway. Glucagon had
      insignificant effects on either PDG or GLDH pathways. Intracellular [15N]
      glutamate formed from [2-15N] glutamine was removed partially by transamination
      to alanine, aspartate and serine and partially by translocation to an
      extracellular compartment. Acidosis, PTH and insulin enhanced the formation of
      [15N] alanine with little effect on [15N] aspartate. PTH, insulin and glucagon
      significantly stimulated the production of [15N]serine, whereas acidosis had
      little effect. The translocation of intracellular glutamate was significantly
      increased by acidosis, PTH and insulin and decreased by acute alkalosis. The data
      indicate that: (a) PTH mimicks the effect of acute acidosis on renal glutamine
      metabolism, that is, augmented glutamine metabolism through both PDG and GLDH
      pathways and stimulated the output of intracellular glutamate. This effect might
      be mediated via decreased activity of the Na(+)-H+ exchanger associated with
      cellular acidification and/or through a second messenger; (b) insulin, but not
      glucagon, increased glutamine uptake and metabolism, and simultaneously enhanced
      output of intracellular glutamate sufficiently to stimulate the PDG pathway; and
      (c) overall, glucagon had little effect on glutamine metabolism by OK cells
      compared with either PTH or insulin.

PMID- 7731177
TI  - [Helping the victims of domestic violence. Traces of blows].

PMID- 7731178
TI  - [Interview with Eliane Affolter, responsible for the course: "Sensibilization for
      humanitarian aid". Going on a mission].

PMID- 7731179
TI  - [Plain information does not protect the environment. Modern man acts in
      opposition to his knowledge].

PMID- 7731180
TI  - [He who experiences pressure will pass it on].

PMID- 7731181
TI  - [Under the coercion of a nursing institution].

PMID- 7731182
TI  - [The story of a scapegoat. "They stuck together like the Mafia"].

PMID- 7731183
TI  - [Between autonomy and the danger to personal safety].

PMID- 7731185
TI  - [Patients have rights--what about the nursing personnel?].

PMID- 7731184
TI  - [Abused women in an emergency unit--an inquiry by Krankenpflege. "Don't cry, but
      scream"].

PMID- 7731186
TI  - [Violence: mirror of self, mirror of the other].

PMID- 7731187
TI  - [Power and weakness].

PMID- 7731188
TI  - [The nursing rounds].

PMID- 7731189
TI  - [Hemofiltration, hemodiafiltration, biofiltration. Methods and indications in
      continuous kidney replacement in the emergency unit 1].

PMID- 7731191
TI  - [Endoscopic splitting of the carpal tunnel].

PMID- 7731190
TI  - [Prevention of contractures].

PMID- 7731192
TI  - [Patients with stomas among the severely handicapped in our society].

PMID- 7731193
TI  - [Laparoscopic cholecystectomy without the use of gas].

PMID- 7731194
TI  - [Does nursing need ethics?].

PMID- 7731195
TI  - Parent and student preferences for services in a school-based clinic.
AB  - As a component of program planning for a school-based clinic in a suburban high
      school, a sample of 199 students and 196 parents were surveyed about preferences
      for health services. Parents and students were asked about health services
      desired and level of interest. Student overall interest in health services was
      less than parent interest, although both groups indicated at least a moderate
      level of interest. Both students and parents reported interest in availability of
      comprehensive services, including general health services, reproductive health
      services, and counseling services. The process of polling parents and students
      serves dual purposes of informing the population about school-based clinics, as
      well as gathering information to attempt to match the health services offered
      with needs identified.

PMID- 7731196
TI  - Teaching about sexual orientation by secondary health teachers.
AB  - Less than half of a random sample (N = 211) of high school health teachers
      formally teach about homosexuality. When taught, it most commonly is taught for
      less than one class period. Only one-in-four teachers perceived themselves as
      very competent in teaching about homosexuality. This is not surprising given the
      fact that teachers were most likely to identify the mass media as the most
      commonly used source of information regarding homosexuality. One-in-five teachers
      claimed students in their classes often used abusive language when describing
      homosexuals. One-third of health teachers indicated gay and lesbian rights are a
      threat to the American family and its values. However, one-third of the health
      teachers perceived the schools were not doing enough to help homosexual
      adolescents. Finally, more than half the health teachers indicated gay/lesbian
      support groups would not be supported by their school administrator. Perceptions
      and behaviors regarding adolescent homosexuality varied by the teachers' gender,
      age, educational level, and teaching status regarding homosexuality.

PMID- 7731197
TI  - Measurement of self-efficacy for diet-related behaviors among elementary school
      children.
AB  - Health promotion interventions intended to improve dietary behavior frequently
      incorporate self-efficacy as a construct to enhance behavior change. This paper
      presents results from a study to establish psychometric properties of a scale to
      measure children's self-efficacy for selecting healthful food. As part of a
      series of pilot studies to develop instrumentation for the Child and Adolescent
      Trial for Cardiovascular Health (CATCH), data were collected on third and fourth
      grade students (n = 1,127). Data analyses were conducted to estimate internal
      consistency, test-retest reliability, factorial validity, and criterion related
      validity. Results revealed acceptable estimates of internal consistency for the
      dietary self-efficacy scale (coefficient alpha = .84). Self-efficacy was strong
      associated with the children's usual food choices, accounting for about 34% of
      variance (Multiple R = .58). Findings support using such an instrument for
      evaluating intervention programs addressing nutrition behavior and for studies to
      determine the association of self-efficacy to dietary behavior or related
      constructs.

PMID- 7731198
TI  - Correlates of HIV risk among young adolescents in a large metropolitan midwestern
      epicenter.
AB  - This paper examines levels of participation in and correlates of AIDS-related
      risk behavior for young adolescents in high-risk communities as determined by
      proxy indicators such as rates of reported STDs and adolescent pregnancies.
      Seventh and eighth grade students from two middle schools and ninth grade
      students from the receiving high school were surveyed. Descriptive and
      inferential techniques examined grade, racial, behavioral, and gender differences
      in participation in risk (substance use and sexual activity) and protective (use
      of condoms and use of condoms and foam) behaviors. Grade, race, and sexual
      activity were significant correlates of both licit and illicit drug use. Gender,
      grade, race, and licit and illicit drug use were significant correlates of sexual
      activity. Results demonstrate that not only are adults and older teens at risk in
      these communities, but younger adolescents also are at risk. Findings indicate a
      need for comprehensive HIV prevention programs at younger ages.

PMID- 7731199
TI  - Creating capacity: a research agenda for school health education.

PMID- 7731200
TI  - A team approach to delivery of EPSDT services in the Pittsburgh, Pennsylvania,
      Schools.

PMID- 7731201
TI  - Opinions of rural Texas parents concerning elementary school health education.
AB  - Parents of elementary school children in rural east-central Texas were surveyed
      about their attitudes toward and knowledge of Comprehensive School Health
      Education. Data indicated widespread support for health education compared to
      other subject areas. Parents felt alcohol and other drugs, nutrition, and first
      aid were the most important topics to be covered in elementary school, while
      sexuality, cancer, and stress were the least important. Parents were most
      comfortable discussing alcohol and other drugs, family life, and growth and
      development with their children and least comfortable discussing exercise,
      cancer, and sexuality. Implications for school health programs are discussed.

PMID- 7731202
TI  - Speaking fundamental frequency changes over time in women: a longitudinal study.
AB  - Archival recordings of the human voice are a relatively untapped resource for
      both longitudinal and cross-sectional research into the aging voice. Through the
      availability of collections of old sound recordings, speech pathologists and
      voice scientists have access to a wealth of data for research purposes. This
      article reports on the use of such archival data to examine the changes in
      speaking fundamental frequency (SFF) in a group of Australian women's voices over
      the past 50 years, and discusses the benefits and problems associated with using
      archival data. Recordings made in 1945 of women were compared with recordings of
      the same women made in 1993 to investigate the changes in SFF with age. The
      results demonstrate a significant lowering of SFF with age in this group of
      Australian women. The implications for the interpretation of cross-sectional data
      on the aging voice, the use of archival data in voice research, and the need for
      further research using archival data are discussed.

PMID- 7731203
TI  - Biomechanical analysis of the pharyngeal swallow in postsurgical patients with
      anterior tongue and floor of mouth resection and distal flap reconstruction.
AB  - The purpose of this study was to examine changes in the biomechanics of
      pharyngeal swallow after surgery in eight patients (six men and two women) with
      anterior tongue and floor of mouth resections with distal flap reconstruction.
      Eight normal age-matched subjects were also studied. Swallowing performance was
      assessed following a standardized protocol with videofluoroscopy preoperatively
      and at 1 and 3 months postoperatively for the oral cancer patients. The normal
      subjects received a single videofluoroscopic study. Computer-assisted
      biomechanical analysis was used to mark the movements of specific oropharyngeal
      structures over time throughout the swallow of calibrated boluses. Statistical
      analyses revealed that tongue base, pharyngeal wall, hyoid, laryngeal, and
      cricopharyngeal movements during the swallow were altered significantly after
      surgery for the cancer patients. Some oropharyngeal structural movements differed
      from those of normal control subjects before surgery. In this study,
      biomechanical measures indicated that there was recovery in some aspects of the
      pharyngeal swallow in this patient group. The duration of tongue base to
      pharyngeal wall contact, which was significantly reduced preoperatively and at 1
      month after surgery, increased significantly to within normal levels by the 3
      month postoperative evaluation. Duration of laryngeal closure and the onset of
      laryngeal closure relative to cricopharyngeal opening also improved significantly
      to within normal levels by the 3-month postoperative evaluation.

PMID- 7731204
TI  - Breathing patterns during spontaneous speech.
AB  - Lung volumes, speech intensity, the linguistic location of inspirations, and the
      variability of each, were studied during spontaneous speech in 6 healthy young
      women over 7 to 10 sessions each, using respiratory inductance plethysmography.
      Although average lung volume levels were within the vital capacity range
      previously reported for speech (Hixon, Goldman, & Mead, 1973), significant inter-
      and intrasubject variability was observed. This variability was considerable for
      some subjects (average initiation lung volume varying between 42 and 63% VC over
      the sessions) and relatively small for others (between 47 and 53% VC). Some of
      the lung volume variation was associated with changes in mood state, examined by
      self-report questionnaire at each measurement occasion. Linguistic factors were
      important influences in the lung volume variation. The majority of breaths in the
      conversations and monologues preceded structural (clause) boundaries. The volume
      of air inspired preutterance was found to be linked to the length of the ensuing
      breath group in each of our 6 subjects, as longer breath groups, spanning up to
      seven clauses in the spontaneous speech, were anticipated by inspiring to a
      higher lung volume. The subjects used a comfortable speaking intensity range,
      which varied for different individuals and sessions over 4 to 18 dB. Increases in
      speech intensity within individual ranges were not associated with increased lung
      volumes. The data provide novel insight into associations between physiological
      and linguistic factors in the control of speech breathing, and are suggestive of
      the existence of neural planning of the respiratory system, in anticipation of
      the demands of the utterance.

PMID- 7731206
TI  - Effect of implicit and explicit "rule" presentation on bound-morpheme
      generalization in specific language impairment.
AB  - This study addressed whether generalization of a trained bound morpheme to
      untrained vocabulary stems differs between children with specific language
      impairment (SLI) and children with normal language (NL) under two controlled
      instructional conditions. Twenty-five children with NL and 25 children with SLI
      matched for age served as subjects. Contrasts between affixed and unaffixed words
      highlighted the affixation "rule" in the "implicit-rule" condition. The "rule"
      was verbalized by the trainer in the "explicit-rule" condition. Bimodal
      generalization results occurred in both subject groups, indicating that
      generalization was not incremental. Chi-square analyses suggested that the SLI
      group generalized the bound morpheme less often than the NL group under the
      explicit-rule training condition. The findings add to those that indicate
      children with SLI have a unique language-learning style, and suggest that the
      explicit presentation of metalinguistic information during training may be
      detrimental to bound-morpheme generalization by preschool-age children with SLI.

PMID- 7731205
TI  - Presence, completeness, and accuracy of main concepts in the connected speech of
      non-brain-damaged adults and adults with aphasia.
AB  - A standard rule-based system was used to evaluate the presence, accuracy, and
      completeness of main concepts in the connected speech of 20 non-brain-damaged
      adults and 20 adults with aphasia. Main concepts form a skeletal outline of the
      most important information (or "gist") in a message. The interjudge and
      intrajudge reliability of the main concept scoring system and the test-retest
      stability of scores were acceptable. The non-brain-damaged group produced
      significantly more Accurate/complete main concepts, and significantly fewer
      Accurate/incomplete, Inaccurate, and Absent main concepts than the group with
      aphasia. However, when the performance of individual subjects was evaluated, what
      best discriminated the performance of subjects with aphasia from that of non
      brain-damaged subjects was not the number of main concepts they failed to mention
      but the accuracy and completeness of the main concepts they did produce. Measures
      of main concept production may be a clinically useful complement to other
      measures of communicative informativeness and efficiency.

PMID- 7731207
TI  - "No shoes; they walked away?": effects of enhancements on learning and using
      Blissymbols by normal 3-year-old children.
AB  - The present investigation studied the effects of enhancements on the learning,
      retention, transfer to the unlearned form, and use of Blissymbols in 40 normal 3
      year-old children. The subjects, seen individually, learned either 12 standard
      Blissymbols (SBS) or the same 12 symbols in the enhanced form (EBS). The symbols
      were introduced with short explanations. The number of trials taken to reach >
      90% correct identification, the number of symbols selected appropriately to
      complete a communicative act, the number of symbols correctly identified a week
      after the acquisition phase was completed, and the number of symbols correctly
      identified in the untrained form of Blissymbols were determined. The results
      demonstrated that the subjects learned EBS faster than SBS, remembered more EBS
      than SBS in the retention task, did not differ in the communicative use of SBS
      and EBS, and were affected more negatively when presented with SBS than EBS in a
      task where the untrained form was presented. The results are discussed in terms
      of how very young children might benefit more from an illustration system such as
      EBS than from an orthographic system such as SBS.

PMID- 7731208
TI  - Effect of utterance length and meaningfulness on the speech initiation times of
      children who stutter and children who do not stutter.
AB  - The purpose of this study was to determine the effect of utterance length and
      meaningfulness on the speech initiation times of children who stutter and
      children who do not stutter. Subjects were 36 elementary school students (half of
      whom stutter, matched by age, grade, and gender). Each child repeated short
      meaningful, long meaningful, and long nonce utterances in response to a visual
      cue. Nonstuttering, stuttering-only, and stuttering-plus (children with
      concomitant speech and/or language problems) children responded differently to
      utterance length and meaningfulness. This suggests that the three groups may
      process speech motor events for verbal responses differently.

PMID- 7731209
TI  - Sentence comprehension in children with specific language impairment: the role of
      phonological working memory.
AB  - This study examined the influence of phonological working memory on sentence
      comprehension in children with specific language impairment (SLI). Fourteen
      children with SLI and 13 with normal language (NL) participated in two tasks. In
      the first, a nonsense word repetition task (index of phonological working
      memory), subjects repeated nonsense words varying in length from one syllable to
      four. In a sentence comprehension task, subjects listened to sentences under two
      conditions varying in linguistic redundancy (redundant, nonredundant). On the
      nonsense word repetition task, between- and within-group analyses revealed that
      subjects with SLI repeated significantly fewer 3-syllable and 4-syllable nonsense
      words. On the sentence comprehension task, between- and within-group analyses
      determined that subjects with SLI comprehended significantly fewer redundant
      (longer) sentences than nonredundant (shorter) sentences. A positive correlation
      was found between subjects' performance on the nonsense word repetition and
      sentence comprehension tasks. Results were interpreted to suggest that children
      with SLI have diminished phonological working memory capacity and that this
      capacity deficit compromises their sentence comprehension efforts.

PMID- 7731210
TI  - Questions concerning facilitated communication: response to Duchan.

PMID- 7731211
TI  - Validity of facilitated communication intervention: response to Duchan.

PMID- 7731212
TI  - Evaluation of a wide range of amplitude-frequency responses for the hearing
      impaired.
AB  - The long-term average frequency spectrum of speech was modified to 25 target
      frequency spectra in order to determine the effect of each of these spectra on
      speech intelligibility in noise and on sound quality. Speech intelligibility was
      evaluated using the test as developed by Plomp and Mimpen (1979), whereas sound
      quality was examined through judgments of loudness, sharpness, clearness, and
      pleasantness of speech fragments. Subjects had different degrees of sensorineural
      hearing loss and sloping audiograms, but not all of them were hearing aid users.
      The 25 frequency spectra were defined such that the entire dynamic range of each
      listener, from 5 dB above threshold to 5 dB below UCL, was covered. Frequency
      shaping of the speech was carried out on-line by means of Finite Impulse Response
      (FIR) filters. The tests on speech reception in noise indicated that the Speech
      Reception Thresholds (SRTs) did not differ significantly for the majority of
      spectra. Spectra with high levels, especially at low frequencies (probably
      causing significant upward spread of masking), and also those with steep negative
      slopes resulted in significantly higher SRTs. Sound quality judgments led to
      conclusions virtually identical to those from the SRT data: frequency spectra
      with an unacceptably low sound quality were in most of the cases significantly
      worse on the SRT test as well. Because the SRT did not vary significantly among
      the majority of frequency spectra, it was concluded that a wide range of spectra
      between the threshold and UCL levels of listeners with hearing losses is suitable
      for the presentation of speech energy. This is very useful in everyday listening,
      where the frequency spectrum of speech may vary considerably.

PMID- 7731213
TI  - Speech recognition in amplitude-modulated noise of listeners with normal and
      listeners with impaired hearing.
AB  - The effect of amplitude-modulated (AM) noise on speech recognition in listeners
      with normal and impaired hearing was investigated in two experiments. In the
      first experiment nonsense syllables were presented in high-pass steady-state or
      AM noise to determine whether the release from masking in AM noise relative to
      steady-state noise was significantly different between normal-hearing and hearing
      impaired subjects when the two groups listened under equivalent masker
      conditions. The normal-hearing subjects were tested in the experimental noise
      under two conditions: (a) in a spectrally shaped broadband noise that produced
      pure tone thresholds equivalent to those of the hearing-impaired subjects, and
      (b) without the spectrally shaped broadband noise. The release from masking in AM
      noise was significantly greater for the normal-hearing group than for either the
      hearing-impaired or masked normal-hearing groups. In the second experiment,
      normal-hearing and hearing-impaired subjects identified nonsense syllables in
      isolation and target words in sentences in steady-state or AM noise adjusted to
      approximate the spectral shape and gain of a hearing aid prescription. The
      release from masking was significantly less for the subjects with impaired
      hearing. These data suggest that hearing-impaired listeners obtain less release
      from masking in AM noise than do normal-hearing listeners even when both the
      speech and noise are presented at levels that are above threshold over much of
      the speech frequency range.

PMID- 7731214
TI  - Accuracy of speech intelligibility index predictions for noise-masked young
      listeners with normal hearing and for elderly listeners with hearing impairment.
AB  - This study examined whether the accuracy of Speech Intelligibility Index (SII)
      predictions is affected by subject age when between-groups auditory sensitivity
      differences are controlled. SII predictive accuracy was assessed for elderly
      listeners with hearing impairment (EHI) and for young noise-masked listeners with
      normal hearing (NMN). SII predictive accuracy was poorer for the EHI subjects
      than for the NMN subjects across a range of test conditions and stimuli. Speech
      test redundancy, speech presentation level, signal-to-babble ratio, and babble
      level also affected SII predictive accuracy. The results suggest that the speech
      recognition difficulties experienced in noise by elderly listeners do not result
      solely from reduced auditory sensitivity.

PMID- 7731215
TI  - Linking visual and kinesthetic imagery in lipreading instruction.
AB  - The purpose of this study was to replicate van Uden's (1983) finding that
      watching oneself speak improves lipreading of visually confusable nonsense words.
      Specifically, this replication focused on an older group of subjects whose
      educational experience varied widely in the emphasis given to spoken
      communication. Four groups of 12 young-adult subjects who are deaf participated
      in evaluating two aspects of training: (a) source of video feedback (self or
      trainer), and (b) timing of feedback (during speech production or after speech
      production). Mean posttest results indicated significantly increased accuracy in
      identifying items that had been trained. The group that viewed self-speech after
      speech-production practice also demonstrated generalization to test items that
      were not trained. On the combined list of both trained and untrained items, both
      groups that viewed their own speech achieved significant gains compared to
      pretest scores, but those that viewed the trainer's speech did not. Response time
      (RT) during pre- and posttesting was measured using a computer-generated waveform
      display to calculate the interval between stimulus offset and response onset.
      Results are reported for 13 subjects with > or = 50% speech intelligibility for
      words in sentences. Although there were no differences attributable to training
      conditions, there was an overall increase in the regularity of the identification
      responses after training (measured by the standard deviation of RTs) and a
      generalization of the improvement to the untrained items. The results of this
      study substantiate the beneficial effects of multisensory feedback by practicing
      lipreading of one's own speech production. This finding appears to apply even to
      young-adult subjects who are deaf and whose habituated speech patterns may be
      quite distinct from those of talkers with normal hearing.

PMID- 7731216
TI  - Comparing reliability of perceptual ratings of roughness and acoustic measure of
      jitter.
AB  - Acoustic analysis is often favored over perceptual evaluation of voice because it
      is considered objective, and thus reliable. However, recent studies suggest this
      traditional bias is unwarranted. This study examined the relative reliability of
      human listeners and automatic systems for measuring perturbation in the
      evaluation of pathologic voices. Ten experienced listeners rated the roughness of
      50 voice samples (ranging from normal to severely disordered) on a 75 mm visual
      analog scale. Rating reliability within and across listeners was compared to the
      reliability of jitter measures produced by several voice analysis systems
      (CSpeech, SoundScope, CSL, and an interactive hand-marking system). Results
      showed that overall listeners agreed as well or better than "objective"
      algorithms. Further, listeners disagreed in predictable ways, whereas automatic
      algorithms differed in seemingly random fashions. Finally, listener reliability
      increased with severity of pathology; objective methods quickly broke down as
      severity increased. These findings suggest that listeners and analysis packages
      differ greatly in their measurement characteristics. Acoustic measures may have
      advantages over perceptual measures for discriminating among essentially normal
      voices; however, reliability is not a good reason for preferring acoustic
      measures of perturbation to perceptual measures.

PMID- 7731217
TI  - Judgments of stuttered and nonstuttered intervals by recognized authorities in
      stuttering research.
AB  - The study reported in this paper gathered judgments of stuttering on brief (5.0
      sec) audiovisual speech samples taken from six adults who stuttered. Judgments
      were made by 10 highly experienced authorities on stuttering treatment and
      research, located in seven different universities or clinical research centers.
      Results showed considerable agreement between pairs of judges working in the same
      center, but large and potentially fundamental differences were identified in the
      amount of stuttering recorded in different centers. Approximately 40% of the 5.0
      sec speech intervals used in this study were assigned the same judgment, either
      Stuttered or Nonstuttered, by all judges on two judgment occasions. The
      possibility that these intervals may serve as a core for establishing an across
      center standard for behavioral judgments of stuttering is discussed.

PMID- 7731218
TI  - Perspectives on the Edinburgh study of speech breathing.
AB  - This article offers critical perspectives on the Edinburgh study of speech
      breathing reported in this journal (Draper, Ladefoged, & Whitteridge, 1959) and
      elsewhere (Draper, Ladefoged, & Whitteridge, 1960; Ladefoged, Draper, &
      Whitteridge, 1958). These perspectives concern: (a) errors in establishing a
      backdrop of mechanical information; (b) discrepancies between data and statements
      about them; (c) counterpredictive features between data and other knowledge about
      breathing; and (d) inadequacies in acquiring, portraying, and interpreting
      electromyographic information relative to the muscular contributions of different
      parts of the breathing apparatus.

PMID- 7731219
TI  - Middle latency auditory responses in males who stutter.
AB  - Little research exists that explores subcortical function in people who stutter.
      One study suggested that auditory middle latency response Wave Pb was prolonged
      in subjects who stutter as compared to controls. Other studies have suggested
      that Pb was generated within the thalamic portion of the reticular system. MLRs
      were recorded from 10 males who stutter and 10 controls using a variety of filter
      passbands in response to clicks presented binaurally at various rates. The
      latency of Pb was found to be significantly shorter in the group of subjects who
      stutter.

PMID- 7731220
TI  - Programmed stuttering treatment for children: comparison of two establishment
      programs through transfer, maintenance, and follow-up.
AB  - Two different Establishment programs, Delayed Auditory Feedback (DAF) and Gradual
      increase in Length and Complexity of Utterance (GILCU), for improving the fluency
      of school-age children who stutter, were compared. The programs were carried out
      by 12 clinicians under supervision with 24 clients (12 elementary and 12
      junior/senior high school) in the schools. Both programs produced important
      improvement in fluency in 23/24 (96%) of the children in a reasonable time period
      (7.9 hours). Generally, the two programs were similar in performance. The only
      difference (between GILCU and DAF) was that the GILCU program provided initially
      for better generalization of fluency. Transfer and Maintenance programs (10.4
      hours) demonstrated that the children from the two Establishment programs
      performed in a similar manner and that the Transfer and Maintenance Programs were
      helpful. In a total of 18.3 hours of establishment, transfer, and maintenance
      treatment, 11 subjects, who completed the programs, reduced their stuttering from
      7.9 SW/M to .8 SW/M at a 14-month follow-up showing that the children had
      maintained their fluency. Clinicians' performances contributed to the
      effectiveness and efficiency of the programs.

PMID- 7731221
TI  - Effect of familiarity on word duration in children's speech: a preliminary
      investigation.
AB  - Young children's productions of novel words were used to investigate the
      influence of word familiarity on vowel and word duration. Ten children, 18 to 21
      months old, produced tokens of phonologically individualized words (from one to
      four words) over 12 experimental sessions. Comparisons of means for the
      individualized words revealed that productions in the second half of the sessions
      were significantly shorter (both in their vowel and overall duration) than those
      in the first six sessions. When mean durations of productions were derived for
      each child, the effect held for word durations. Vowel durations differed in the
      same direction, but the difference was not statistically significant. Under these
      controlled conditions, familiarity seemed to influence the duration of early
      productions of novel words. These findings are discussed as evidence of word
      specific motor maturation in early lexical acquisition.

PMID- 7731222
TI  - Glottal area and vibratory patterns studied with simultaneous stroboscopy, flow
      glottography, and electroglottography.
AB  - The purpose of the present study was to examine the relationship between
      variations in glottal area and vibratory patterns during phonation studied with
      stroboscopy and glottographic methods. Two normal speaking male and three female
      subjects were examined by means of simultaneous stroboscopy, flow glottography,
      and electroglottography. Estimations were made of the glottal area from pressure
      and flow data using the formula described by van den Berg. Significant
      correlations were found for the male phonations between estimations and
      measurements of the minimum glottal area (glottal insufficiency). Estimations of
      the peak glottal area were also significantly correlated to measured peak glottal
      area for values below 25 mm2. The estimated minimum area tended to be higher,
      whereas the estimated peak area values were lower than the corresponding glottal
      area measurements. This might be explained by variations in glottal and
      supraglottal geometry for different modes of phonation and by sub- and
      supraglottal acoustic interaction. Several glottographic parameters for the male
      phonations were highly correlated with the measurements of glottal insufficiency
      and also differed significantly between normal, pressed, and breathy
      hypofunctional modes of phonation. The presence of a hump in the first part of
      the closed phase for the flow glottogram seems to indicate that a clearly visible
      mucosal wave is present during vocal fold vibration.

PMID- 7731223
TI  - Oncogenes: 20 years later. Keystone, Colorado, January 5-11, 1995. Abstracts.

PMID- 7731224
TI  - Keystone symposium. Plant cell biology: mechanisms, molecular machinery, signals
      and pathways. Taos, New Mexico, January 7-13, 1995. Abstracts.

PMID- 7731225
TI  - Keystone symposium. Drug delivery: barriers to drug transport and the design of
      novel therapeutic agents. Hilton Head Island, South Carolina, January 7-13, 1995.
      Abstracts.

PMID- 7731226
TI  - Keystone symposium. Molecular toxicology. Copper Mountain, Colorado, January 9
      15, 1995. Abstracts.

PMID- 7731227
TI  - Keystone symposium. Ribozymes: basic science and therapeutic applications.
      Breckenridge, Colorado, January 15-21, 1995. Abstracts.

PMID- 7731229
TI  - Keystone symposium. Molecular aspects of viral immunity. Keystone, Colorado,
      January 16-23, 1995. Abstracts.

PMID- 7731228
TI  - Keystone symposium. Mucosal immunity: new strategies for protection against viral
      and bacterial pathogens. Keystone, Colorado, January 16-23, 1995. Abstracts.

PMID- 7731230
TI  - Keystone symposium. Genetic networks. Santa Fe, New Mexico, January 20-26, 1995.
      Abstracts.

PMID- 7731231
TI  - Bacterial Chromosomes. Keystone symposium on molecular and cellular biology.
      Santa Fe, New Mexico, January 6-12, 1995. Abstracts.

PMID- 7731232
TI  - Keystone symposium. Cancer cell invasion and motility. Tamarron, Colorado,
      February 5-11, 1995. Abstracts.

PMID- 7731233
TI  - Keystone symposium. Functions of the cytoskeleton in cell growth, organization
      and differentiation. Taos, New Mexico, February 19-25, 1995. Abstracts.

PMID- 7731234
TI  - Keystone symposium. Host-fungus pathogenic interactions. Taos, New Mexico,
      February 25-March 3, 1995. Abstracts.

PMID- 7731235
TI  - Keystone symposium. Synapse formation and function: the neuromuscular junction
      and central nervous system II. Tamarron, Colorado, February 26-March 4, 1995.
      Abstracts.

PMID- 7731237
TI  - Keystone symposium. Processing enzymes: biochemistry, genetics and clinical
      relevance. Lake Tahoe, California, March 2-8, 1995. Abstracts.

PMID- 7731236
TI  - Keystone symposium. Heat shock (stress) proteins in biology and medicine. Santa
      Fe, New Mexico, February 27-March 5, 1995. Abstracts.

PMID- 7731238
TI  - Keystone symposium. Apoptosis (programmed cell death). Tamarron, Colorado, March
      5-11, 1995. Abstracts.

PMID- 7731239
TI  - Keystone symposium. Molecular approaches to marine ecology and evolution. Santa
      Fe, New Mexico, March 5-11, 1995. Abstracts.

PMID- 7731240
TI  - Keystone symposium. The molecular basis for differences between the sexes.
      Tamarron, Colorado, February 12-18, 1995.

PMID- 7731241
TI  - Keystone symposium. Discovery of therapeutic agents. Lake Tahoe, California,
      March 9-15, 1995. Abstracts.

PMID- 7731242
TI  - Keystone symposium. Molecular mechanisms in Tuberculosis. Tamarron, Colorado,
      February 19-25, 1995. Abstracts.

PMID- 7731243
TI  - Keystone symposium. Molecular motors. Taos, New Mexico, February 19-25, 1995.
      Abstracts.

PMID- 7731244
TI  - Nurses: a vital force in health care.

PMID- 7731245
TI  - How do you know if your paycheck is correct?

PMID- 7731246
TI  - An overview of seasonal affective disorder.

PMID- 7731247
TI  - Tuberculosis today.

PMID- 7731248
TI  - Urinary incontinence: a study of teaching practices of nursing students.

PMID- 7731249
TI  - Marketing nursing: every patient deserves a nurse.

PMID- 7731250
TI  - Clinical characteristics of fatal pulmonary embolism in a referral hospital.
AB  - OBJECTIVE: To determine the clinical characteristics of hospitalized patients who
      died of pulmonary embolism, confirmed by evaluative autopsy. DESIGN: We
      retrospectively analyzed a series of autopsy cases of pulmonary embolism at a
      tertiary-care center for the period Jan. 1, 1985, through Dec. 31, 1989. MATERIAL
      AND METHODS: The medical and autopsy records of all hospitalized patients with
      autopsy-proven fatal pulmonary embolism were reviewed. Cases of tumor emboli, fat
      emboli, and contributory-only thromboembolic disease were excluded from the
      study. Specific symptoms and signs, diagnostic studies, and prophylactic measures
      were noted. RESULTS: Among 2,427 autopsies performed during the 5-year study
      period, death in 92 (3.8%) was clinically and pathologically judged to be caused
      by pulmonary embolism. No risk factors were noted in only 11 patients (12%).
      Prophylaxis against thromboembolism was used in 46%. Classic symptoms were often
      absent: dyspnea was present in only 59%, chest pain in only 17%, and hemoptysis
      in 3%. Pulmonary embolism was considered in 49% of the 92 patients and was
      correctly assigned as the cause of death on the death certificate or in the
      medical records in 32%. Testing for venous thromboembolic disease was performed
      in 22%. Comorbidity was present in most patients: 54% had guarded or poor
      prognoses independent of pulmonary embolism. CONCLUSION: The usual signs and
      symptoms associated with pulmonary embolism did not adequately identify most of
      our patients who died of pulmonary embolism. The reasons included the absence of
      these signs and symptoms, inability to communicate (for example, sedated or
      comatose patient), sudden death from acute massive pulmonary embolism, and
      presence of comorbid factors.

PMID- 7731251
TI  - Collagenous colitis: mucosal biopsies and association with fecal leukocytes.
AB  - OBJECTIVE: To determine the frequency of patchy colonic involvement, fecal
      leukocytosis, and association with celiac sprue in a large cohort of patients
      with collagenous colitis. DESIGN: We conducted a retrospective review of the
      medical records of 172 consecutive Mayo Clinic patients in whom collagenous
      colitis had been diagnosed between 1982 and 1993. METHODS: For each of the 172
      patients, the medical record was reviewed to determine the frequency of (1) fecal
      leukocytosis; (2) characteristic histologic findings in the rectum and the
      sigmoid, descending, and ascending colon; and (3) small bowel biopsy findings
      consistent with celiac sprue. RESULTS: The presence of fecal leukocytes was noted
      in 64 of 116 patients (55%) who had undergone assessment for fecal leukocytosis.
      On analysis of histologic findings, 113 of 123 rectal, 116 of 121 sigmoid, and 68
      of 70 descending colon biopsy specimens were diagnostic of collagenous colitis.
      Small bowel biopsies were performed in 45 patients who did not have a history of
      small intestinal disease: 1 had celiac sprue and 44 had normal findings. Two
      other patients had previously diagnosed celiac sprue. CONCLUSION: The finding of
      fecal leukocytes in 55% of patients with collagenous colitis confirms the
      inflammatory basis of this disease. Biopsy specimens obtained by flexible
      sigmoidoscopy seem sufficient to establish the diagnosis in most patients, and
      colonoscopic biopsy of the more proximal area of the colon is usually
      unnecessary. Celiac sprue infrequently accompanies collagenous colitis; thus,
      routine small bowel biopsy is not warranted.

PMID- 7731252
TI  - Improved detection of silent cardiac ischemia with a 12-lead portable
      microprocessor-driven real-time electrocardiographic monitor.
AB  - OBJECTIVE: To compare a microprocessor-driven real-time 12-lead
      electrocardiographic monitoring device with Holter monitoring for detection of
      ischemia. DESIGN: Electrocardiographic monitoring was conducted in 110 patients
      at bed rest or undergoing surgical procedures. MATERIAL AND METHODS: In three
      groups of patients, simultaneous monitoring with a 12-lead real-time device and a
      2-channel Holter system was performed to detect ischemic episodes. The
      differences in the number of ischemic events and the total time of ischemia
      revealed by the two devices were analyzed statistically. RESULTS: In patients
      with coronary artery disease, more ischemic ST-segment shifts were detected by
      the 12-lead device than by Holter monitoring (44 versus 16 events; P < 0.05).
      Total time of ischemia was also greater with the 12-lead device (879 versus 273
      minutes; P < 0.05). Ischemia was detected by both techniques in 6 patients, only
      by the 12-lead device in 12, and only by Holter monitoring in 1. Neither device
      detected ischemia in control subjects. The 12-lead device had an advantage in
      detecting inferior ischemia, and it identified an additional 13 patients with
      unstable angina who had changes in T-wave polarity but did not exhibit ST-segment
      shifts. CONCLUSION: The 12-lead real-time electrocardiographic monitoring device
      is superior to Holter monitoring in detecting and facilitating real-time
      identification of myocardial ischemia in patients at bed rest.

PMID- 7731253
TI  - Intracerebral hemorrhage in liver transplant recipients.
AB  - OBJECTIVE: To analyze possible causative mechanisms for intracranial hemorrhage
      after orthotopic liver transplantation. DESIGN: We conducted a retrospective
      survey of medical records and a case-control comparison in patients who had
      undergone liver transplantation during the period 1986 through 1992. MATERIAL AND
      METHODS: In a group of 8 patients with intracranial hemorrhage after orthotopic
      liver transplantation and a control series of 207 patients who had undergone
      liver transplantation but did not have intracranial hemorrhage, we summarized
      pertinent clinical and laboratory data and statistically analyzed potential risk
      factors for hemorrhage. RESULTS: In the eight study patients, intracerebral
      hematomas were located in the parietal or frontal lobe in six, the cerebellum in
      one, and the putamen in one. Autopsy demonstrated a Candida-associated mycotic
      aneurysm in one of the eight patients, and one had disseminated aspergillosis. No
      statistically significant differences in thrombocytopenia, hypertension,
      extracranial bleeding sites, or cyclosporine-related neurotoxicity were found
      when these patients were compared with the control series. Bacteremia or fungemia
      was found in five of the eight patients with intracerebral hemorrhages (62%) but
      in only 11% of the control group (P = 0.03; Fisher's exact test). CONCLUSION:
      Overwhelming infections, thrombocytopenia, or both may have a role in
      intracerebral hemorrhage after liver transplantation.

PMID- 7731254
TI  - Barbara McClintock--Nobel laureate geneticist.

PMID- 7731255
TI  - Endometriosis: current management.
AB  - OBJECTIVE: To review the clinical features, theories of pathogenesis, and current
      treatment of endometriosis-associated pain and infertility. DESIGN: We review the
      manifestation of endometriosis and the possible mechanisms that lead to its
      symptoms, examine the efficacy of current therapeutic options for pelvic pain and
      infertility, and provide specific recommendations for treatment based on the
      current literature. MATERIAL AND METHODS: Endometriosis is the presence of
      hormonally responsive endometrial tissue occurring outside the uterine cavity.
      This condition may be asymptomatic but is often found in association with pelvic
      pain or infertility (or both). The precise pathogenesis has not been clearly
      established but likely involves retrograde menstruation with subsequent seeding
      of endometrial glands at extrauterine sites. The definitive diagnosis and staging
      of endometriosis are performed by laparoscopy. Various strategies have been used
      to treat endometriosis including expectant, medical, surgical, and combination
      management. RESULTS: The efficacy of treatment varies for pelvic pain and
      infertility. Endometriosis-associated pain may respond to both medical and
      surgical management. The use of medical therapy for endometriosis-associated
      infertility is not supported by current studies. Surgical management of
      infertility may be efficacious when pelvic anatomy is distorted because of
      endometriosis. The use of superovulation strategies and in vitro fertilization
      has been shown to be effective in overcoming endometriosis-associated
      infertility. CONCLUSION: Pelvic pain and infertility in the presence of
      endometriosis necessitate individualization of therapy to achieve treatment
      goals. Neither medical nor surgical management is efficacious in all
      circumstances. As a better understanding of the pathogenesis of endometriosis
      evolves, treatment of this perplexing condition will probably continue to
      improve.

PMID- 7731256
TI  - Adjunctive therapy in the management of patients with acute myocardial
      infarction.
AB  - Adjunctive therapy for acute myocardial infarction should include aspirin, beta
      adrenergic blocking agents, and, in most patients, consideration of the use of
      angiotensin-converting enzyme inhibitors, especially if left ventricular function
      is reduced. Heparin has an important adjunctive role in enhancing early vessel
      patency in patients who receive tissue-type plasminogen activator and in
      decreasing the frequency of reocclusion of an infarct-related artery during any
      thrombolytic therapy. Heparin must also be administered to all patients who
      undergo primary angioplasty. Intravenously administered nitroglycerin and orally
      administered nitrates are probably most effective in patients with symptomatic
      ischemia. Calcium channel blockers and prophylactic antiarrhythmic agents are not
      indicated for most patients with acute myocardial infarction. Currently,
      insufficient evidence is available to recommend the widespread use of
      intravenously administered magnesium sulfate in the setting of acute myocardial
      infarction. In patients with ischemic pain, judicious intravenous administration
      of morphine can provide relief. Use of warfarin sodium should be reserved for
      patients at risk for left ventricular mural thrombus. Although the use of lipid
      lowering agents after myocardial infarction has been controversial, recent
      studies have demonstrated the importance of such therapy for secondary prevention
      of death and morbidity.

PMID- 7731257
TI  - Propafenone-induced peripheral neuropathy.
AB  - Propafenone hydrochloride, a class IC antiarrhythmic drug, is used in the
      treatment of ventricular and supraventricular arrhythmias. Herein we describe a
      patient with episodic jabbing and crushing pain in his hands and feet, aching in
      his forearms, and hyperesthesias of his extremities. He had been taking
      propafenone for 1 year because of ventricular arrhythmias. Results of a nerve
      conduction velocity test were abnormal. Electron microscopic findings on a sural
      nerve biopsy specimen represented distal small fiber neuropathy. Findings on a
      thermoregulatory sweat test and on autonomic tests were abnormal, compatible with
      a distal small fiber neuropathy. To our knowledge, peripheral neuropathy has not
      previously been reported to occur with use of propafenone. In this patient,
      propafenone seemed to be responsible for the development of peripheral
      neuropathy, which resolved after use of the drug had been discontinued.

PMID- 7731258
TI  - Rhabdomyolysis after correction of hyponatremia due to psychogenic polydipsia.
AB  - Severe neurologic complications resulting from correction of hyponatremia are
      common, but reports of nonneurologic sequelae are scarce. This article describes
      a patient in whom rhabdomyolysis developed during correction of severe
      hyponatremia attributable to psychogenic polydipsia. Relevant material about
      volume regulation in the cell is presented, and a potential mechanism of cell
      damage is proposed. This case report emphasizes the importance of monitoring for
      nonneurologic complications during correction of hyponatremia.

PMID- 7731259
TI  - Cortical petechial hemorrhage, leukoencephalopathy, and subacute dementia
      associated with seizures due to cerebral amyloid angiopathy.
AB  - Although cerebral amyloid angiopathy is a well-known cause of cerebral lobar
      hemorrhage, subacute dementia, seizures, and acute encephalopathy without lobar
      hemorrhage are infrequently recognized as manifestations of this disease. In this
      report, we describe a case of cerebral amyloid angiopathy in a 74-year-old woman
      who had subacute progressive dementia and a superimposed rapid acute neurologic
      deterioration associated with seizures and the presence of cerebral edema on
      computed tomographic scans and leukoencephalopathy and cortical petechial
      hemorrhages on magnetic resonance imaging. A diagnosis of cerebral amyloid
      angiopathy in conjunction with small cortical infarcts and petechial hemorrhages
      was confirmed by antemortem biopsy. This clinical and radiologic picture is being
      increasingly recognized as characteristic of cerebral amyloid angiopathy.

PMID- 7731260
TI  - Aspirin idiosyncrasy in systemic mast cell disease: a new look at mediator
      release during aspirin desensitization.
AB  - OBJECTIVE: To report the clinical responses and mediator-release profiles of an
      aspirin-sensitive man with systemic mast cell disease during aspirin
      desensitization. MATERIAL AND METHODS: We quantified the release of six mediators
      during aspirin desensitization. RESULTS: Although aspirin was administered
      cautiously with an initial dose of 20 mg, successful aspirin desensitization
      necessitated complete monitoring and resuscitation capabilities of a medical
      intensive-care unit for 4.5 days because of frequent, severe anaphylactoid
      responses. To our knowledge, this is the first report of a pronounced increase in
      plasma levels of the vasodilator peptide calcitonin gene-related peptide during
      episodes of aspirin-induced hypotension. Increases in plasma levels of calcitonin
      and serum levels of tryptase paralleled those of calcitonin gene-related peptide,
      but plasma levels of calcitonin remained increased for up to 18 hours. Urinary
      excretion of histamine and 1-methyl-4-imidazoleacetic acid also showed
      precipitous, although delayed, increases. Excretion of the prostaglandin D2
      metabolite 11 beta-prostaglandin F2 alpha followed a bimodal pattern during
      aspirin desensitization; after severe hypotensive responses, the maximal value
      was more than 490,000 pg/mL, but the level decreased to less than 100 pg/mL after
      therapeutic serum levels of salicylate were attained. CONCLUSION: These data
      suggest that the hypotensive responses to aspirin in some patients with systemic
      mast cell disease may result from the combined effects of several mediators.

PMID- 7731261
TI  - 50-year-old man with fever and rhinorrhea.

PMID- 7731262
TI  - Point-of-care testing.

PMID- 7731263
TI  - An endangered ethic--the capacity for caring.

PMID- 7731264
TI  - Fatal pulmonary embolism: old pitfalls, new challenges.

PMID- 7731265
TI  - Warfarin therapy.

PMID- 7731266
TI  - Warfarin therapy.

PMID- 7731267
TI  - Cerebral computed tomography before initiation of anticoagulant therapy.

PMID- 7731268
TI  - Treatment of nonsteroidal anti-inflammatory drug-induced enteropathy.

PMID- 7731269
TI  - Ethoxyresorufin and pentoxyresorufin O-dealkylation by hepatic microsomes from
      female Fischer 344 rats: effects of age and diet.
AB  - Ethoxyresorufin (EROD) and pentoxyresorufin (PROD) O-dealkylase activities, and
      contributions of the P450 cytochromes CYP1A1, CYP2B1 and 2, CYP2C6 and CYP2C12 to
      these metabolic activities, were evaluated in hepatic microsomes from ad libitum
      and calorie restricted female Fischer 344 rats across an age continuum from 1 to
      26 months. The presence of CYP1A in microsome preparations was confirmed by
      western blot analysis. Uninduced levels of EROD and PROD peak in very young
      animals, decline to about 3 months of age, and do not exhibit an additional
      substantive decline after about 3 months of age. Monoclonal antibody (MAb) 1-7-1
      (anti-CYP1A) strongly inhibited EROD activity in all microsome preparations, with
      the highest levels of inhibition in microsomes from 1- and 3-month-old AL
      animals. PROD activity in 1-month uninduced animals was apparently not
      attributable solely to CYP2B1 and 2, since it was inhibited by about 30% in both
      1- and 26-month-old AL rats by an MAb specific for CYP2C12. However, in CR rats,
      CYP2C12 did not contribute to PROD activity. Approximately 40% of PROD activity
      in old AL rats and 20% of PROD activity in old CR rats was inhibited by an MAb
      specific for CYP2C6. These data indicate that long-term calorie restriction
      modulates either the expression or post-translational modification patterns of
      constitutive P450 isozymes in rats as they age, with P450 patterns in calorie
      restricted rats more closely resembling those found in young animals.

PMID- 7731270
TI  - Effect of age on cholesterol uptake and utilization by rat adrenals: I.
      Internalization of lipoprotein-derived cholesteryl esters.
AB  - Previous studies from this laboratory have documented a progressive age-related
      decline in trophic hormone (or second messenger cAMP) stimulated corticosterone
      production in isolated adrenocortical cells. In the current study, we examined
      the possibility that the aging process exerts this effect by interfering with an
      early step in the delivery of lipoprotein-derived cholesteryl esters to the cell.
      As such, we monitored the ability of two different rat adrenocortical cell model
      systems (intact perfused adrenal glands and primary cultures of adrenocortical
      cells from 5- and 18- to 20-month-old rats) to internalize lipoprotein
      cholesteryl esters, and to convert the newly internalized cholesteryl esters to
      corticosterone production. The results indicate that lipoprotein (hHDL3 and rHDL)
      cholesteryl ester internalization (by both the endocytic and 'selective'
      pathways) is comparable in adrenocortical cells of the young and old rats.
      However, despite this, both the mass of corticosterone produced and the ratio of
      newly internalized (radiolabeled) cholesteryl ester incorporated into
      corticosterone is dramatically reduced in cells of the older animals. Thus, the
      lipoprotein uptake pathway appears to be intact in adrenals of older rats, but
      the intracellular processing of internalized cholesteryl ester is defective.

PMID- 7731271
TI  - Effect of age on cholesterol uptake and utilization by rat adrenals: II.
      Lipoproteins from young and old rats.
AB  - The current study examines whether age-related changes in high density
      lipoproteins (HDL) influences how these particles are handled by adrenal cells.
      It appears that HDL from 18- to 20-month-old Sprague-Dawley rats show a seven- to
      eightfold increase in content of apolipoprotein E compared to HDL from 2- to 5
      month-old rats. The 'aged' particles show increased binding to susceptible
      hepatic membranes, and show a doubling in whole particle endocytosis by cortical
      cells of the perfused adrenal gland and by isolated adrenal cells from all rats
      regardless of age. Despite this twofold increase in particle uptake, the increase
      in total cholesteryl ester uptake by either the perfused adrenal or incubated
      adrenal cells is minor, amounting to less than 10% of the total cholesteryl ester
      internalized. This discrepancy occurs since the high apo E content of the 'aged'
      HDL only affects cholesteryl ester uptake by the 'endocytic' pathway; uptake via
      the 'selective' pathway (where cholesteryl ester is separated from the rest of
      the particle at the cell surface and directly internalized) is not altered.

PMID- 7731272
TI  - Molecular evidence for the presence of a developmental gene in the lowest
      animals: identification of a homeobox-like gene in the marine sponge Geodia
      cydonium.
AB  - During the development of higher animals, morphogenetic programs are switched on
      which are frequently controlled by homeotic genes. Until now these genes have not
      been identified in the lowest animals, the marine sponges. Since sponges show (i)
      an antero-posterior and/or dorso-ventral axis during embryogenesis and (ii) a
      complex differentiation pattern during spicula formation, we hypothesized that in
      sponges homeotic genes--if present--are also involved in the control of these
      processes. Therefore, we searched for homeobox or homeobox-like sequences in the
      marine sponge Geodia cydonium. Here we describe a homeobox-like sequence from
      these animals; it was isolated from a cDNA library of an adult specimen. The
      deduced amino acid sequence of the complete homeodomain shares over 70%
      similarity with other homeodomain sequences, including those from hydra, insects
      and vertebrates. These data indicate that the sponge homeodomain-like sequence is
      similar with respect to structure to those of other animals and may suggest that
      the sponge homeodomain-like sequence(s) might function during developmental
      processes and/or during spiculogenesis in a similar manner to that known for
      higher animals.

PMID- 7731273
TI  - Vasomotor reactivity and catecholamine, arginine vasopressin plasma levels during
      ageing and development in rats.
AB  - Vascular reactivity, heart rate responses to vasoconstrictor and/or vasodilatator
      agents and catecholamine and arginine vasopressin turnover were studied in
      normotensive Wistar Kyoto (WKY), spontaneously hypertensive (SHR), normolipemic
      Brown Norway (BN) and spontaneously hyperlipemic Yoshida (YOS) anaesthetized rats
      at 2, 6 and 18 months of age. In this study, we investigated whether ageing and
      development could affect cardiovascular reactivity to vasoactive substances and
      catecholamine and arginine vasopressin turnover. No significant changes in the
      pressor responses to noradrenaline and to carotid sinus baroreceptor stimulation
      were observed nor were there significant alterations in reflex tachycardia and
      bradycardia. Arginine vasopressin plasma levels also did not change with ageing
      and development. On the other hand, the hypotensive responses to isoprenaline
      decreased in old rats, acetylcholine relaxation effect increased with ageing and
      development in some rat strains (BN and YOS) and catecholamine plasma levels
      increased with ageing and development. Our results indicate that during ageing
      and development, vascular responsiveness to vasoconstrictor and/or vasodilatator
      agents, as well as amine turnover, may increase, decrease or not change at all
      depending on the neurotransmission system studied, and on the experimental model
      and/or animal tested.

PMID- 7731274
TI  - Cell-mediated immune response and cytokine production in idiopathic senile
      anorexia.
AB  - Some aspects of humoral and cell-mediated immunity and the capacity of peripheral
      blood mononuclear cells (PBMCs) of fourteen elderly persons with idiopathic
      anorexia to produce several cytokines, such as tumor necrosis factor alpha (TNF
      alpha), interleukin-1 beta (IL-1 beta), interleukin-6 and interferon-gamma (IFN
      gamma), were studied and the results were compared with those obtained in a
      control group of ten age-matched, normal weight healthy subjects. In addition,
      spontaneous and induced production of these cytokines was also measured in
      cultures of PBMCs of fourteen healthy young individuals as a control group of
      age. A significant decrease in CD2 (pan T-cells) and CD4 (T-helper) lymphocyte
      subpopulations, but unchanged CD8 (T-suppressor) subset, and a reduced response
      in delayed cutaneous hypersensitivity tests were observed in senile underweight
      anorectic patients. Monocyte counts did not show significant differences between
      patients and control subjects. The spontaneous release by PBMCs of all the
      cytokines measured did not differ between the anorectic and either the elderly or
      young control group. A significant increase in IL-6 production after mitogen
      stimulation with tetradecanoylphorbol acetate (TPA) and phytohemagglutinin (PHA)
      after 24 and 48 h of culture, as well as a greater induced TNF alpha production
      after 48 h of incubation with the same mitogens, was found in the anorectic
      patients as compared with the elderly controls. However, stimulated production of
      both IL-1 beta with TPA and of IFN gamma with PHA did not differ significantly
      between anorectics and aged controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731275
TI  - Medicare reimbursement for preventive care. Changes in performance of services,
      quality of life, and health care costs.
AB  - A randomized, controlled trial was conducted to assess the effects of a financial
      and office systems intervention to increase preventive care in physicians'
      offices for patients aged 65 years or older. A total of 1,914 patients from 10
      primary-care medical practices in central North Carolina were randomized within
      practices to an intervention and a usual-care control group. The intervention
      consisted of full Medicare reimbursement to physicians for preventive care and
      health promotion packages (thus making these services free for patients), regular
      prompting of physicians to routinely schedule preventive care visits, a new
      office system in which nurses carried out many preventive procedures, and a form
      for charting preventive care. The performance of screening tests dramatically
      increased in the intervention group relative to control (P < 0.001), but there
      was evidence of lack of follow-up of abnormal findings by physicians. At the 2
      year follow-up, there were minimal differences between intervention and control
      groups in health-related quality-of-life indicators. Relative to the $294 per
      patient 3-year cost to Medicare for waivered services, the intervention was
      reimbursed-cost neutral or slightly cost reducing ($190 over 3 years) for
      Medicare. It is concluded that adding reimbursement for preventive services to
      Medicare--even with the office systems changes made in this study--will not by
      itself lead to effective implementation of preventive services in community
      medical practices. To enhance patient benefit from preventive services, greater
      attention needs to be focused on an organized approach to patient follow-up.

PMID- 7731276
TI  - Search behavior and choice of physician in the market for prenatal care.
AB  - The authors examine how 963 expectant mothers in Florida searched for and
      selected a prenatal care provider. Overall, the results suggest that women search
      for prenatal care in much the same way as search theory predicts. Nevertheless,
      the amount of search reported is surprisingly small. Less than a quarter of the
      women in the survey seriously considered more than one physician, and even among
      this group, less than 60% actually spoke to or visited a second physician.
      Because of the timing, importance, and relative frequency of pregnancy, it is
      probably easier to search for a prenatal care provider than it is to search for
      most other medical services. Consequently, if search is this uncommon for
      prenatal care providers, it is probably even less common for other procedures. As
      they search for and choose a prenatal care provider, pregnant women rely most
      heavily on information from friends and acquaintances. Women facing high
      coinsurance rates or whose choices are constrained by HMO or Medicaid coverage
      rely less on recommendations from friends and acquaintances. These women also
      appear less satisfied with their choice of prenatal care provider.

PMID- 7731277
TI  - Severity of depression in prepaid and fee-for-service general medical and mental
      health specialty practices.
AB  - This study compares severity of depression for patients of general medical
      clinicians, psychiatrists, and nonphysician therapists receiving prepaid or fee
      for-service care. Cross-sectional severity comparisons were conducted among 715
      outpatients with current major depression or dysthymia, by independent
      assessment. Severity was assessed by counts of current and lifetime depressive
      symptoms, prognostic and treatment response indicators, and global measures of
      psychological and physical sickness. Patients of psychiatrists were the most
      psychologically ill, patients of nonphysician therapists were intermediate, and
      general medical patients were least ill; but even in the general medical sector,
      depression severity was at least ill; but even in the general medical sector,
      depression severity was at least moderate. No differences in global physical
      sickness by specialty remained after demographic adjustment. General medical
      patients whose depression had been detected were only slightly sicker than
      undetected cases. Type of payment was not consistently related to either
      psychological or physical aspects of sickness, and payment did not interact with
      specialty. Mental health specialists, especially psychiatrists, encountered more
      severely depressed patients, but patients in all sectors were sick enough to
      warrant treatment. Even undetected patients in the general medical sector were
      relatively sick, raising questions about gatekeeper policies. There was no
      evidence of a greater severity gradient by specialty in prepaid care. Because
      payment was unrelated to severity, treatment implications are similar under
      prepaid and fee-for-service care. Implications for clinical practice, public
      policy, and outcomes research design are discussed.

PMID- 7731278
TI  - The effect of physician factors on the cesarean section decision.
AB  - The number of deliveries by cesarean section (c-section) has increased
      dramatically. Clinical and demographic factors have not adequately explained the
      increased rate, however. This study investigates the role of nonclinical (i.e.,
      physician) factors in explaining variations in c-section rates, including the
      physician's training/experience, financial and convenience incentives, and
      practice characteristics. The study measures the impact of these factors on the
      decision to perform a c-section rather than opting for vaginal delivery,
      controlling for a host of patient and hospital characteristics. Physician effects
      are evaluated in terms of their overall contribution to the explanatory power of
      logistic regression models, as well as in terms of specific hypotheses to be
      tested. The analyses are based on 33,233 deliveries performed by 441 physicians
      in 36 hospitals in 1 state during 1989. As a set, physician factors contribute
      more to the explanatory power of the model than do hospital factors, despite
      being added last to the equation. Parameter estimates provide more support for
      the hypothesized effects of physician convenience incentives than
      background/training. The log odds of performing a c-section increase with the
      physician's rate of c-sections in the prior year, delivery on a Friday, and
      delivery between 6 AM and 6 PM, and decrease with the concentration of the
      physician's hospital practice. Patient factors appear much more important than
      both physician and hospital factors, however. Efforts to reduce unnecessary c
      sections should focus on identifying the appropriate clinical indications for c
      section and disseminating this information to physicians.

PMID- 7731279
TI  - Controlling outpatient medical equipment costs through utilization management.
AB  - Utilization management programs have been widely used to control hospital
      inpatient costs, but little is known about their potential to control outpatient
      costs. Claims data covering a 21-month period beginning in January, 1990 were
      analyzed to evaluate the effects of a utilization management program established
      by an insurance carrier to contain costs for durable medical equipment. Four
      items were targeted for review: seat lifts, transcutaneous electrical nerve
      stimulator (TENS) 2 and TENS 4 units, and power-operated vehicles. The program
      was associated with significant reductions (P < 0.05) in order requests, supplier
      charges, and claims payments for three of the four targeted items. Under the
      program, the rate of denials increased significantly (P < 0.05) for two of the
      targeted items. Most of the program's cost savings accrued from a "sentinel" or
      volume effect, not from an increase in denials. These findings provide further
      evidence of the cost containment potential of utilization management. Focused
      utilization management programs that target provider groups, patient populations,
      or service sectors experiencing high volume have the greatest chance of achieving
      cost savings.

PMID- 7731280
TI  - A comparative study of seven measures of patient satisfaction.
AB  - The acceptability of satisfaction as a quality indicator is qualified by several
      well known measurement problems. This study examines the variability in
      satisfaction evaluations related to different measurement methods and the effect
      of response biases on reported satisfaction. Satisfaction evaluations using seven
      different, commonly used measures of patient satisfaction were obtained from the
      same sample of respondents. The seven measures were: 1) a global measure of
      satisfaction using a visual analogue scale; 2) a multidimensional measure of
      satisfaction based on the Patient Satisfaction Questionnaire using an evaluation
      response format (poor, fair, good, very good, excellent); 3) a two-item overall
      evaluation of quality using the evaluation response format; 4) a six-item
      attitude measure of general satisfaction using a five-point Likert agree-disagree
      response format; 5) a four-item attitude measure of satisfaction with physician,
      using the agree-disagree response format; 6) a four-item measure of behavioral
      intention; and 7) willingness-to-pay in dollars. The percentage of favorable
      evaluations of care ranged from 63% to 82% across six of the seven measures.
      Willingness-to-pay does not appear to be a valid measure of satisfaction.
      Correlations were highest between measures with similar response formats.
      Although an oppositional response bias was not found, a very substantial
      acquiescent response bias was detected. Acquiescence reduced the internal
      consistency of three multiple-item measures, the general and physician attitude
      and behavioral intention measures, to levels unacceptable even for group
      comparisons. Between highly and nonacquiescent respondents, levels of
      satisfaction were somewhat lower for the multidimensional measure of satisfaction
      and significantly lower for the two attitude satisfaction measures. Highly
      acquiescent respondents were older, less well educated, and in poorer health than
      nonacquiescent subjects. Results of satisfaction evaluations dependent on the
      measurement method used, and unreliability of measurement may be a significant
      problem in satisfaction measurement, especially for the oldest and most ill
      patients.

PMID- 7731281
TI  - The influence of gender on physician practice style.
AB  - As more women enter medicine, intriguing questions arise about how physician
      gender impacts practice style. To measure this influence in primary care
      encounters, 118 male and 132 female adult new patients, having no stated
      preference for a specific physician, were randomly assigned to university
      hospital primary care residents, and their initial encounters were videotaped.
      Forty-eight male and 33 female physicians participated. Patient health status was
      assessed before the visit with the Medical Outcomes Study Short-Form General
      Health Survey. Physician practice style was evaluated by using the Davis
      Observation Code to analyze videotapes of each initial visit. Patient
      satisfaction with medical care was assessed with satisfaction questionnaires.
      Contrary to prior reports, the difference between male and female physicians in
      total time spent with patients was small and statistically insignificant, and
      diminished further when controlling for patient gender and health status. Female
      physicians, however, were observed to engage in more preventive services and to
      communicate differently with their patients. These differences in practice style
      appear to explain partially the observed higher patient satisfaction scores for
      female physicians. This study underscores the importance of careful measurement
      and control of potential confounding factors in clarifying the impact of
      physician gender on practice style.

PMID- 7731282
TI  - Who is responsible for care given during the inpatient stay? A preliminary
      examination of attending and procedure physicians in Medicare's new data system.

PMID- 7731283
TI  - Sources of AIDS information for parents and children.

PMID- 7731284
TI  - Estimating nursing home episodes from a sample of discharges. The importance of
      adjusting for prior and subsequent stays.

PMID- 7731285
TI  - [Trends of child mortality form tumors in Catalonia (1975-1992)].
AB  - BACKGROUND: Childhood mortality from tumors has decreased in industrialized
      countries. The aim of this paper is to study the trend of mortality from tumors
      in children (under 15 years old) during the period 1975-1992. METHODS: Using data
      from the Department of Health and Social Security's Register of Mortality, age
      group standardized (to world population) mortality rates for each sex were
      analyzed. Analysis was carried out on total mortality caused by childhood tumors
      and on main causes of death (leukemia, brain cancer, non-Hodgkin lymphoma, bone
      cancer and non-specified tumors). A Poisson's regression model was used to
      analyze mortality trends. RESULTS: Childhood tumors caused 8.7% of all deaths in
      boys and 8.5% of all deaths in girls between 1990-1992. Thus, standardized
      mortality rates have decreased significantly, in 1975-1977 standardized mortality
      rates for boys and girls were 71.20 and 68.05 respectively, in 1990-1992 these
      rates had fallen to 55.45 and 41.30. The annual percentage decrease in cancer
      mortality rates for boys was 2% and for girls was 3.1%. Main causes of deaths
      were leukemia and brain cancer. CONCLUSIONS: Between 1975-1992 a significant
      downward trend in childhood tumors mortality has been observed, more prominent in
      main causes of death and in girls. The principal explanation for this trend is an
      increased survival, consequence of changes in childhood tumors therapy.

PMID- 7731286
TI  - [Anti-beta 2 glycoprotein I antibodies. Relationship with antiphospholipid
      antibodies and thrombosis].
AB  - BACKGROUND: Anti-beta 2-glycoprotein I antibodies (a beta 2GPI) were studied in
      patients with diseases or clinical symptoms related to antiphospholipid
      antibodies (aPl) with the aim of establishing a relationship between both
      antibodies and these clinical manifestations. METHODS: The a beta 2GPI antibodies
      were determined by enzymeimmunoassay in a group of 94 altruist blood donors and
      135 patients (98 with systemic lupus erythematosus, 21 cases of primary
      antiphospholipid syndrome, 10 cases with idiopathic Sneddon syndrome and 6 with Q
      fever). The lupus anticoagulating-type aPl antibodies were determined in the same
      subjects by kaolin coagulation time and the Russell's viper venom time while
      anticardiolipin-type IgG, IgM and IgA isotypes were determined by
      enzymeimmunoassay. The a beta 2GPI antibodies were related with the aPl
      antibodies, fetal losses and history of thrombosis by a contingency table with
      Yates correction in the first two parameters and means comparison by the
      Students' t test for the history of thrombosis. RESULTS: The aPl and a beta 2GPI
      antibodies in the control group were negative. In the group of patients the
      latter antibodies were positive in 33.6% (33 cases) of the patients with lupus,
      57% (12 cases) of the patients with primary antiphospholipid syndrome, in one of
      the patients with the Sneddon syndrome and in none of the patients with Q fever.
      The aPl antibodies were positive in 26.5% of the patients with lupus and in 100%
      of the cases with primary antiphospholipid syndrome or Q fever and negative in
      all the cases with idiopathic Sneddon syndrome. A significant relationship was
      found between the a beta 2GPI antibodies and thrombotic manifestations (p = 0.01)
      or obstetric complications (p < 0.04). A dependent relationship was observed in
      both autoantibodies (aPl and a beta 2GPI) (p < 0.01). CONCLUSIONS: There is a
      significant relationship between the antiphospholipid antibodies and the anti
      beta 2-glycoprotein I antibodies in addition to a relationship with thrombotic
      symptoms or obstetric complications.

PMID- 7731287
TI  - [Changes in heroin administration route and frequency of human immunodeficiency
      virus infection].
AB  - BACKGROUND: Self-administration of drugs by different intravenous routes may
      induce a reduction in the organic complications of drug addiction (DA). The aim
      of this study was to evaluate the changes in the way of drug administration in a
      series of DA individuals in the province of Cadiz, Spain, and the evolution of
      the frequency of infection by the human immunodeficiency virus (HIV) in these
      patients. METHODS: The reports of all the drug users from the province of Cadiz
      admitted to the Detoxication Unit of the Hospital Punta de Europa in Algeciras,
      from January, 1989 to July, 1993 were reviewed. At the time of admission many
      data were evaluated, fundamentally the main route of drug administration, and
      anti-HIV seropositivity. RESULTS: Seven hundred ten drug users were included in
      the study. Ninety-seven percent used mainly heroin. The route of drug
      administration on admission was intravenous in 56.1%, pulmonary in 39.7%,
      inhalatory in 3.2% and oral in 0.8%. Forty-one point seven percent patients were
      seropositive for HIV. The frequency of the use of the intravenous route
      throughout the semesters analyzed was I/89: 85.7%, II/89: 89.6%, I/90: 80%,
      II/90: 80.8%, I/91: 59.8%, II/91: 50%, I/92: 44.9%, II/92: 39%, I/93: 34.3% (p <
      0.00001). The use of the respiratory route significantly increased. The
      percentage of anti HIV positivity in the drug users evaluated was 67.4, 80.8,
      56.4, 46.9, 40.7, 34.1, 30.6, 36.3, 23.2% (p < 0.00001), respectively for the
      same periods. The decrease in the use of the intravenous route and the reduction
      in anti HIV seropositivity demonstrated a correlation coefficient of 0.91 with a
      confidence interval from 0.62 to 0.98 (p < 0.05). CONCLUSIONS: The decrease, over
      time, in the use of the intravenous route for heroin administration in the
      collective analyzed was significantly associated with a decrease in HIV infection
      in these patients.

PMID- 7731288
TI  - [Tumors in childhood].

PMID- 7731289
TI  - [Magnetic resonance angiography].

PMID- 7731290
TI  - [Polycystic endodermal heterotopy of the atrioventricular node].
AB  - We present the two first Spanish cases about the endodermic heterotopia of the
      atrioventricular node. This is an infrequent and probably congenital lesion, with
      a not well known histogenesis and associated with heart blocks and sudden death,
      which affects women in most cases. The first observation attaches a 55 years-old
      woman with an acute leukemia who died during the first chemotherapy treatment.
      The second observation affects a 25 years-old woman, with previous heart blocks,
      who died suddenly. A complete post-mortem study was done in both cases (including
      cardiac conduction system) with conventional histopathological study and
      extensive immunohistochemical panel. Ultrastructural study of first case was
      done. In both cases a multicystic and tubular lesion was found in the
      atrioventricular node region. It was lined by two or more cubic and polyhedral
      cell layers. In the cystic lumina an eosinophilic material, which corresponded to
      acid and neutral mucosubstances was found. The maximal lesion's diameter were:
      0.9 and 1.3 cm, respectively. Immunohistochemically it was detected in both cases
      strong positivity for cytoqueratines, EMA, CEA and focally for chromogranin A and
      calcitonin. The immunohistochemical results in both cases express and endodermic
      differentiation (with neuroendocrine fenotipe).

PMID- 7731291
TI  - [Establishing an ethics committee: the experience of the Hospital Consortium of
      the Parc Tauli de Sabadell].

PMID- 7731292
TI  - [Report on excimer laser in ophthalmology].

PMID- 7731293
TI  - [Confessions of a writer of a biomedical journal. The experience of Medicina
      Clinica].

PMID- 7731294
TI  - [Mediastinal adenopathy as presentation form of occult thyroid papillary
      carcinoma].

PMID- 7731295
TI  - [Is Addison disease predictable in polyglandular type I autoimmune syndrome?].

PMID- 7731297
TI  - [What to do with linguistic foreignisms?].

PMID- 7731296
TI  - [Penicillin ineffectiveness in a case of necrotising fasciitis caused by
      Streptococcus pyogenes].

PMID- 7731298
TI  - [Mixed cryoglobulinemia and hepatitis C virus infection: value of the treatment
      with interferon].

PMID- 7731299
TI  - [Assessment of the performance of sabbatical leave: Hospital Clinic i Provincial
      of Barcelona (1990-1991). Research Committee of the Hospital Clinic i Provincial
      of Barcelona].
AB  - BACKGROUND: The development of an evaluation protocol for assessing the
      scientific contribution and the impact on medical care of the sabbatical leaves
      granted in a large Spanish teaching hospital. METHODS: The sabbatical leaves for
      all faculty staff of the Hospital Clinic i Provincial of Barcelona (HCPB) were
      analyzed since 1980 trough 1991. The scientific production analysis was done
      according to the impact factor (IF) score of the Science Citation Index.
      Descriptive statistical techniques as well as parametric and non-parametric tests
      were used for comparisons. RESULTS: A total of 52 sabbatical leaves was analyzed
      of all 60 leaves granted (87%). Mean duration of the leave was 7.94 +/- 3.86
      months. The scientific production includes 89 original articles published in peer
      reviewed medical journals, with a total score of 300.82 IF points (mean score:
      5.78 +/- 7.12 IF points by leave). There were significant differences in the mean
      duration, number of papers published and IF points score by sabbatical leave
      between the Medicine, Surgery and Other Departments. In 16 cases (31%) there was
      a professional promotion following the sabbatical leave and in 20 cases (39%) an
      academic promotion. In 27 cases (60%) there was no promotion after the leave.
      Most of the faculty staff physicians (96%) are still employed in the same
      institution, and believe that the sabbatical leave has significantly contributed
      to their promotion (67%). A high percentage (94%) has also been able to develop
      afterwards the methods and techniques learned during the sabbatical leave.
      CONCLUSIONS: The experience of the Hospital Clinic of Barcelona in granting
      sabbatical leaves has been highly positive. The scientific performance of the
      individuals on leave is high. Our institution has been able to add and develop
      most of the techniques and methods learned overseas. The future of the sabbatical
      leaves in other Spanish Universities and Hospitals should be regarded as a high
      priority target. The performance of these leaves is supported by its scientific
      results, that could be quantified.

PMID- 7731300
TI  - [Delirium in an elderly population admitted at a general hospital].
AB  - BACKGROUND: Delirium is an organic mental disorder frequently seen in elderly
      patients admitted to hospital for medical or surgical diseases. The prevalence,
      triggering factors, the relationship with prior existence of dementia and the
      evolution of delirium were studied. METHODS: One hundred eight elderly patients
      admitted to the Internal Medicine, General Surgery and Traumatology Departments
      of the Hospital Clinic i Provincial in Barcelona, Spain were randomly selected
      with clinical evaluation being performed following the DSM-III-R diagnostic
      criteria. Likewise a structured clinical interview (CAMDEX) was carried out, and
      the establishment of delirium, the possible causes and its evolution were
      evaluated. RESULTS: Eighteen of the elderly patients studied presented delirium
      at some time during hospital stay. Of these patients 15 had previously been
      clinically diagnosed with dementia. These patients did not require longer
      hospital stay than those not presenting dementia. The most frequent etiology was
      surgery and fever due to an infectious process. In addition to etiologic
      treatment, 12 of the patients also received symptomatic treatment with a
      neuroleptic drug (haloperidol). CONCLUSIONS: Most of the elderly who have
      presented delirium admitted in a general hospital had been diagnosed with
      dementia during hospital stay thus indicating the high comorbidity of the two
      entities. In many cases it is important to carry out symptomatic in addition to
      etiologic treatment to achieve rapid reversibility of the disorder.

PMID- 7731301
TI  - [Effect of 3 hypertensive++ agents on ventricular geometry and function].
AB  - BACKGROUND: To assess the prevalence of left ventricular hypertrophy in
      hypertensive patients referred to an outpatient cardiology unit, and to assess
      its evolution under antihypertensive treatment. METHODS: One hundred and seven
      mild to moderate hypertensive patients were randomized to receive either
      xipamide, verapamil or atenolol. Cross-sectional echocardiography was performed
      in order to assess left ventricular mass and function. RESULTS: Mean age was 56
      years, with a 4:1 female/male ratio. Mean follow-up was 120 days. Left
      ventricular hypertrophy was very common (65%) and decreased to 54% under
      antihypertensive treatment. Left ventricular mass decreased from 134.3 g/m2 to
      118.1 g/m2 (p < 0.001). Concentric hypertrophy was the most common geometric
      pattern (42%), decreasing to 30% with treatment. Xipamide decreased ventricular
      mass by decreasing left ventricular diameters, while verapamil and atenolol
      decreased left ventricular thickness, mainly in septal wall. Systolic function
      was not modified during the treatment period. Diastolic function was not modified
      by xipamide and verapamil, and improved with atenolol. CONCLUSIONS: Left
      ventricular hypertrophy is very frequent when determined by echocardiography and
      all three drugs produced regression of left ventricular hypertrophy in a
      different way with respect to left ventricle geometry, an effect which could have
      potential therapeutic implications.

PMID- 7731302
TI  - [Sabbatical leave, vacation or work?].

PMID- 7731303
TI  - [Treatment of left ventricular dysfunction following acute myocardial infarction:
      impact of the most recently published studies].

PMID- 7731304
TI  - [Hemolytic-uremic syndrome caused by Escherichia coli O157:H7. Detection in
      direct sample of verotoxin-coding genes].
AB  - Hemorrhagic colitis is an enteritis caused by verotoxigenic strains of
      Escherichia coli. Conventional diagnosis requires the identification of the
      microorganism and the demonstration of verotoxin production. The determination of
      toxigenicity in isolated strains and in direct stool samples by the polymerase
      chain reaction (PCR) technique may simplify the diagnosis. Conventional
      coprocultures were performed for the detection of verotoxigenic E. coli O157:H7
      from three stool samples of a patient with hemorrhagic colitis and hemolytic
      uremic syndrome. The production of verotoxin was determined by cell culture and
      the presence of VT1 and VT2 genomic sequences by PCR. Likewise, the latter
      technique was applied to a direct stool sample for detection of the verotoxin
      codiying genes. The specificity of the amplified sequences was confirmed by
      enzyme restriction digestion. Escherichia coli O157:H7 was isolated in two of the
      three samples studied. The strains were toxigenic in the cell culture test at
      titers higher than 1/500 and PCR showed an amplified band of 479 pb corresponding
      to the VT2 codifying gene. The digestion of amplified sequences with the EcoRV
      enzyme led to two bands of 390 and 89 pb confirming the specificity of the
      results. One of the two stool samples studied directly by PCR was positive for
      VT2 with the result being obtained 48 hours after arrival to the laboratory. The
      preliminary results of this study give support to the usefulness of the
      polymerase chain reaction technique in the detection of verotoxin from isolated
      strains of Escherichia coli and in direct stool samples.

PMID- 7731305
TI  - [Glucocorticoids in oncology].

PMID- 7731306
TI  - [Ciguatera: report of an imported case].

PMID- 7731307
TI  - [Pneumothorax secondary to bronchoalveolar lavage].

PMID- 7731308
TI  - [Fever and hypotension following oral administration of mesalazine].

PMID- 7731309
TI  - [Pasteurella pneumotropica sepsis].

PMID- 7731310
TI  - [Psoas abscess secondary to brucellar sacroiliitis].

PMID- 7731311
TI  - [Spanish experts in hypertension].

PMID- 7731312
TI  - [Medical certificate and legal rights: moderate fee is necessary for the
      protection of patients' rights].

PMID- 7731313
TI  - [Care of sick refugees--how shall we handle it? Illegal immigrants as an ethical
      problem in health care].

PMID- 7731314
TI  - [Computerized medical records could be better!].

PMID- 7731315
TI  - [Penicillin should be withdrawn from the list of drugs that district nurses are
      allowed to prescribe].

PMID- 7731316
TI  - [Self evaluation shows that education is potentiated by increased knowledge of
      patient care].

PMID- 7731317
TI  - [The extremely premature infants. A new generation of much desired infants].

PMID- 7731318
TI  - [Vascular endothelial growth factor. A vascular growth factor of high
      specificity].
AB  - Angiogenesis, the formation of new blood vessels, is regulated by angiogenic
      growth factor. Vascular endothelial growth factor (VEGF) is a recently discovered
      growth factor that, in contrast to other growth factors with angiogenic activity,
      acts specifically on the vascular endothelium. VEGF is involved in the induction
      of new blood vessel formation in various physiological and pathological processes
      associated with increased angiogenesis.

PMID- 7731319
TI  - [Is surgery of patients with hip problems performed too late? Good cost-benefit
      effects of hip alloplasty].

PMID- 7731320
TI  - [Greater chance to survive a myocardial infarction. Changed therapeutic methods
      may play an important role].

PMID- 7731321
TI  - [Hepatitis E not only in subtropical regions. A new test indicates its presence
      in Sweden too].

PMID- 7731322
TI  - [Departments of thoracic surgery in China open their doors. Extensive expansion
      for heart surgery].

PMID- 7731323
TI  - [Churg-Strauss syndrome. An unusual but treatable form of systemic vasculitis].

PMID- 7731324
TI  - [Jacob Churg and Lotte Strauss. They were brought together by a mutual destiny].

PMID- 7731325
TI  - [Good quality of life of older patients with hypertension. Equally good effect of
      felodipine and hydrochlorothiazide].

PMID- 7731326
TI  - [Experience with vascular surgery based on cases reported to the Patient
      Insurance Registry. Importance of circulatory control and competent methods].

PMID- 7731327
TI  - [How to solve conflicts in connection with accidents in health care? Patient
      physician relation in malpractice reports].

PMID- 7731328
TI  - [Increasing number of physicians reported for malpractice. Support for reported
      physicians should be increased].

PMID- 7731329
TI  - [Burns may be prevented. Safe use of diathermy apparatus].

PMID- 7731330
TI  - Aboriginal cultural issues for health care services.

PMID- 7731331
TI  - Nurse in profile. Flight nurse, Air Ambulance Service of New South Wales.

PMID- 7731332
TI  - Loss, challenge, change: psychological and physical aspects of hand injury.
AB  - This article discussed the psychological and physical aspects of hand injury. The
      importance of a team approach in establishing the optimum of care to assist the
      patient in maintaining self-esteem, worth and acceptance is emphasized.

PMID- 7731333
TI  - The ANRAC competencies: a comment on method.

PMID- 7731334
TI  - The ANRAC competencies in context.

PMID- 7731335
TI  - Nurse in profile. Interview by Peter Schwab.

PMID- 7731336
TI  - Relapse following various types of multidrug therapy in multibacillary leprosy.

PMID- 7731337
TI  - IgG subclass antibodies to mycobacterial sonicate and recombinant antigens in
      leprosy.
AB  - In this study the IgG subclass antibodies to sonicated preparations of
      Mycobacterium leprae (leprosin A) and BCG (BCG-S) as well as to purified
      recombinant 65 kDa protein of M. leprae (rML65) were analysed in sera from
      leprosy patients and healthy household contacts (HFC) and noncontacts (HNC) in a
      leprosy endemic population. In LBI+ (lepromatous bacterial index positive)
      patients, IgG3 was predominant in the responses to sonicated antigens of M.
      leprae. Following chemotherapy, IgG3 responses were reduced while IgG2 levels
      were increased. On the other hand, IgG response to rML65 was dominated by IgG1 in
      all the patient and control groups. Interestingly, the level of antileprosin A
      IgG antibody in erythema nodosum leprosum (ENL) was similar to that of
      lepromatous groups, while the level of anti-rML65 IgG antibody was significantly
      reduced in ENL. IgG4 antibodies to the antigens studied were only at low levels
      in all groups, including ENL. Significant differences were observed between HNC
      and HFC in the pattern of IgG subclass antibodies to sonicated antigens, even
      though their antigen specific IgG levels were similar. While HNC showed
      equivalent proportion of IgG1 and IgG2 in their responses to leprosin A and BCG
      S, HFC showed a specific increase in IgG1 levels, suggesting that both groups are
      distinctly different. Further studies are required to elucidate the functional
      significance of IgG subclass pattern in pathogenesis and the mechanism of
      immunoregulation resulting in the high levels of IgG1 and IgG3 antibodies to M.
      leprae protein antigens in lepromatous leprosy.

PMID- 7731338
TI  - A study on performance of two serological assays for diagnosis of leprosy
      patients.
AB  - We compared 2 serological tests for the diagnosis of leprosy to test their
      performances. The tests include the serum antibody competition test (SACT) for
      the detection of antibodies to Mycobacterium leprae-specific epitope on 35 KDa
      protein molecule, and M. leprae gelatin particle agglutination assay (MLPA), for
      the detection of antiphenolic glycolipid-1 (PGL-1) antibodies. In both the assays
      a higher serological positivity was seen amongst multibacillary (MB) patients
      than those in paucibacillary (PB) patients. Taking all leprosy patients together,
      the sensitivity of SACT (59.7%) was observed to be statistically comparable to
      that of MLPA (66.9%). However, SACT proved to be more specific (97.7%) than MLPA
      (75.0%). The agreement between these 2 assays was observed to be moderate.

PMID- 7731339
TI  - Immunoreactive antigens of a candidate leprosy vaccine: Mycobacterium habana.
AB  - Mycobacterium habana (M. simiae serovar-1) is a candidate vaccine for
      mycobacterial infections on the basis of the protection shown by this strain. We
      prepared 3 fractions of M. habana, i.e. the cell wall (CW), the cell membrane
      (CM) and the cytosol (CS). Protein antigens of these fractions were resolved by
      SDS-PAGE and subsequently probed with the sera of leprosy and tuberculosis
      patients and also antiBCG antibodies. We saw 3 major protein bands at congruent
      to 33 kD in the CW, congruent to 38 kD in the CM and congruent to 22 kD in the
      cytosol (CS) after coomassie blue staining of the gels. Pool leprosy patients'
      serum had identified proteins of congruent to 26 kD in CW, congruent to 35 and
      congruent to 18 kD in CM and congruent to 24 kD in the CS which have not been
      seen by the TB patient's serum pool. Pool serum of tuberculosis patients has
      identified 1 protein at congruent to 10 kD in the CW and a broad band between 20
      and 24 kD and 1 at congruent to 4 kD in the CM which have not been visualized in
      the pool leprosy patient's serum lane. The proteins of M. habana which are
      recognized only by leprosy antisera or only by tuberculosis antisera could be
      exploited for developing diagnostic agents against these infections.

PMID- 7731340
TI  - Inhibition of the multiplication of Mycobacterium leprae in nude mice by
      intermittent administration of a new rifamycin derivative, 3'-hydroxy-5'-(4
      isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648) combined with
      sparfloxacin.
AB  - Inhibition of the multiplication of Mycobacterium leprae in the footpads of nude
      mice by the oral administration of sparfloxacin, a new quinolone, and 3'-hydroxy
      5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648), selected from a
      series of newly synthesized benzoxazinorifamycins, was studied. When the 2 drugs
      were administered alternately at intervals of 3 or 4 days, (i.e., each drug was
      administered once weekly), or simultaneously once weekly, between 3 and 5 months
      after inoculation of nude mice with M. leprae, 10 mg sparfloxacin and 0.6 mg KRM
      1648 per kg bodyweight were sufficient to prevent multiplication of the
      organisms. Only partial inhibition of multiplication was achieved by alternate
      administration of 5 mg sparfloxacin and 0.3 mg KRM-1648 per kg, as was the case
      for 20 mg sparfloxacin per kg or 1 mg KRM-1648, each drug administered alone once
      weekly. The addition to these 2 drugs of dapsone, administered in the diet in a
      concentration of 0.001 g per 100 g, enhanced their effect. The potential
      usefulness of multidrug regimens including these compounds is considered.

PMID- 7731341
TI  - Vascular surgery of the posterior tibial compartment for plantar ulceration in
      leprosy.
AB  - Traditional surgical decompression of the posterior tibial nerve yields equivocal
      results. The authors postulate that the posterior tibial artery is the most
      compromised structure in the neurovascular compartment and that the best surgical
      results in healing of plantar ulcers are achieved by the rechannelling of the
      blood flow in the posterior tibial artery during posterior tibial neurovascular
      compartment surgery. This procedure has been of benefit to patients with plantar
      ulcers of greater than 7-10 years' duration in whom all other modes of healing
      had failed. It has been undertaken as an outpatient procedure under local
      anaesthesia, supported by postoperative vasodilator drugs. The use of tourniquet,
      antibiotics and surgical interference with the ulcer per se was eschewed. A
      report of 156 patients is presented with follow-up of up to 6 years for the
      earlier cases.

PMID- 7731342
TI  - Assessment of the methods available for testing sensation in leprosy patients in
      a rural setting.
AB  - The aim of this study was to assess the efficacy, practicality and patient
      understanding of 5 methods used for testing sensation in leprosy patients, in a
      rural setting. The tests used were the WHO test, cottonwool, pin-prick,
      monofilaments and the biothesiometer. We concentrated on testing sensation in the
      hands, and the various tests were carried out on 75 patients and 32 controls, all
      taken from villagers living at Kindwitwi Leprosy Village, Tanzania. Our results
      showed that although the WHO test, cottonwool and pin-prick were all easy to use,
      cheap and well accepted they were not sensitive enough to be of any practical
      value. We found that the monofilaments, as well as being cheap and easy to use,
      had great potential value, as the 2-g monofilament could be used as a threshold
      value (indicative of leprosy, but not diagnostic) for protective sensation with a
      combined false-positive and false-negative value of only 4%. Finally, the
      biothesiometer was found to be a precise test that can accurately identify
      leprosy patients from controls and identify patients at risk of ulceration. It
      was, however, associated with its own problems, chiefly those of expense and its
      need of electricity, although we found this latter problem could be easily and
      relatively cheaply solved by the use of a solar powered recharger (Appendix).

PMID- 7731343
TI  - Clofazimine induced cardiotoxicity--a case report.
AB  - A 66-year-old Indian male who had been treated for recurrent erythema nodosum
      leprosum with 300 mg of clofazimine per day for 11 months presented to hospital
      with a 4 week history of severe gastrointestinal upset. Soon after admission he
      developed several short runs of ventricular tachycardia with a morphology
      suggestive of torsade de pointe. The patient had a slightly low magnesium level
      which was corrected within 2 days; however, his rhythm disturbance persisted for
      5 days despite management with intravenous lidocaine. His gastrointestinal
      symptoms abated 2 weeks after clofazimine was discontinued. Subsequent
      investigations showed that the patient had a keratopathy and myelin-type figures
      in his polymorphonuclear white cells similar to that seen with the cardiotoxic
      drugs chloroquine and amiodarone. It is postulated that clofazimine alone or in
      conjunction with electrolyte disturbance was responsible for the patient's
      cardiac arrythmia.

PMID- 7731344
TI  - Trends in leprosy in the Kingdom of Bhutan, 1982-1992.
AB  - An evaluation programme was undertaken 11 years after the introduction of
      multidrug therapy (MDT) into Bhutan, by examining the case notes of 3239 leprosy
      patients who had been under treatment at any time during the period. The
      registered prevalence was found to have fallen markedly, as expected, and this
      had been accompanied by a clear fall in the case detection rate as well. The
      lepromatous rate among new patients rose considerably, giving epidemiological
      hope that the disease may be coming under control. However, no concomitant fall
      in the proportion of child cases was seen. The disability rate at detection rose
      slightly, although numbers were small. New cases were increasingly likely to have
      more highly positive skin smears, and to be self-reported. Programme planners
      should give thought to the implications of these findings.

PMID- 7731345
TI  - Comment: Blister-calendar packs for multiple drug therapy in leprosy.

PMID- 7731346
TI  - Task-oriented short-term training to contract leprosy workers in a national
      leprosy eradication programme.

PMID- 7731347
TI  - Comment: Sensory testing with nylon filaments and pens.

PMID- 7731348
TI  - To mutilate in the name of Jehovah or Allah: legitimization of male and female
      circumcision.
AB  - Female circumcison is practised in Sudan, Somalia, Egypt and a few other Arab and
      Muslim countries. It has triggered a passionate public debate in the West. This
      debate has found somewhat of an echo in the Arab and Muslim world, but some
      Muslim religious circles such as Al-Azhar (Egypt), the most important Islamic
      centre in the world, try to justify it on the basis of sunnah (that is, to
      conform with the tradition of the prophet Mohammed). Male circumcision is
      practised by all Muslims and Jews and also by some Christians in Egypt, in the
      United States and Canada). For different reasons, the debate on this topic is
      still taboo in Western and in Arab and Muslim countries. The object of this study
      is to define the role of Islamic law and Muslim religious leaders in female and
      male circumcision. On purpose, it avoids any use of the word 'Islam', and
      concentrates on the written sources of Islamic law and the opinions of
      contemporary Arab authors, mostly of Egyptian origin. Juridical logic cannot
      acknowledge the distinction between female and male circumcision, both being the
      mutilation of healthy organs which is damaging to the physical integrity of the
      child, whatever the underlying religious motivations. Furthermore, both practices
      violate the Koran: 'Our Lord, You did not create all this in vain' (3:191), and
      '[He] perfected everything He created' (32:7). In our opinion, a god who demands
      that his believers be mutilated and branded on their genitals the same as cattle,
      is a god of questionable ethics. To mutilate children, boys or girls, under the
      pretext that it is for their own good, shows the influence of cynicism and
      fanaticism.

PMID- 7731349
TI  - Towards a comprehensive national policy on drug abuse.
AB  - Drug abuse is complex in its causation and ramifications. No country has been
      able to respond successfully to the problems brought in the wake of drug abuse by
      having recourse to a single strategy. In 1987 the United Nations adopted a
      comprehensive multidisciplinary outline for future activities in drug abuse
      control. This provided, for the first time, a comprehensive framework within
      which countries can elaborate policies and programmes tailor-made to national
      situations. However, in order to facilitate the development and implementation of
      such policies and programmes it is essential that certain conditions exist:
      strong political will at national level; recognition of the need for an
      integrated policy; adequate legal framework and enforcement capability;
      coordinated response at international, national and local level; and recognition
      of drug abuse in planning changes in different sectors.

PMID- 7731350
TI  - The right to die in Canadian legislation, case law and legal doctrine.
AB  - This article discusses moral, social, medical and legal problems pertaining to
      the so-called 'right to die' from the perspective of Canadian criminal
      legislation (the Criminal Code), constitutional law (the Charter of Rights and
      Freedoms) and court rulings. Regarding the latter, the opinions delivered in
      Nancy B v Hotel-Dieu de Quebec and Rodriguez v British Columbia (Attorney
      General) are especially significant. In Rodriguez, the Supreme Court of British
      Columbia unequivocally rejected the petitioner's submission that the Charter of
      Rights and Freedoms guarantees the right to die. This judgment was upheld on
      appeal by both the British Columbia Court of Appeal and the Supreme Court of
      Canada. In addition, the article addresses the complex problem of legislating the
      right to die in Canada. Several options are examined, such as professional
      judgment and advance health care directives including living wills and powers of
      attorney for health care. In this context, the recommendations adopted by both
      the Law Reform Commission of Canada and provincial commissions are analysed.
      Finally, the article discusses the legislation proposed recently in Alberta,
      Manitoba, Newfoundland, Ontario and Saskatchewan. It seems doubtful, however,
      whether a nation-wide solution will be found in the near future.

PMID- 7731351
TI  - Silicone breast implant litigation (Part 1).
AB  - Silicone breast implant litigation has escalated in the past couple of years with
      the Food and Drug Administration (FDA) investigation of silicone gel implants
      which resulted in finally removing the silicone gel implants from the market.
      Plaintiffs have linked various medical problems to the presence of silicone in
      the body. The FDA has stated that there is no medical evidence that silicone
      causes autoimmune disease. Silicone has never been shown to cause breast cancer.
      Breast implants can result in complications such as capsule contracture, gel
      bleed, implant rupture, calcifications around the implants, and possibly
      interference with mammography in the diagnosis of breast cancer. Plaintiffs have
      claimed that the implant manufacturers knew of the defects in the silicone shell
      implant covering, and covered up the facts. The product liability action has
      become a class action, and a proposed settlement has been made in terms of which
      implant recipients with any problems will be reimbursed. Furthermore, there will
      be coverage for future implant problems over the next 30 years. There will still
      be some litigation by those patients who have opted out of the settlement
      agreement.

PMID- 7731353
TI  - Health care 2001: gambling with health care finally pays off.

PMID- 7731352
TI  - The position of Islamic tradition on contraception.
AB  - The first source of Islamic law, the Koran, does not mention contraception. On
      the contrary, most of the 'sayings' (hadith) of the Prophet Mohammed (the second
      source of Islamic law) on the subject, tolerate coitus interruptus (azl). The
      position commonly and historically shared by Islamic jurists coincides with Al
      Ghazali's interpretation according to which, under many circumstances, coitus
      interruptus is a blameworthy but tolerated (makruh) act. However, there has
      always been a minority of jurists opposed to contraception. Analogical reasoning
      (qiyas, the fourth source of Islamic law) makes it possible to legitimize most
      modern contraceptive techniques. Nowadays, because of the risks of
      overpopulation, the majority of Islamic governments have passed family planning
      laws; however among the masses the wrong belief that Islamic law prohibits
      contraception is spreading.

PMID- 7731354
TI  - Competency assessment and attorneys: to consult or not to consult?

PMID- 7731355
TI  - An historical overview of Maryland General Hospital.

PMID- 7731356
TI  - Limiting restraint use for behavior control: the brain injury rehabilitation unit
      as a model.
AB  - Physical or pharmacologic restraints are often used to control the behavior of
      patients who are agitated or who demonstrate behavior that is inappropriate or
      potentially dangerous. Centers that specialize in traumatic brain injury
      rehabilitation treat many patients who manifest agitated behavior. This article
      reviews behavior management within a brain injury rehabilitation setting and
      describes less restrictive restraint systems. A case study of the management of
      an agitated patient with traumatic brain injury is presented. Possible future
      trends in the use of restraint systems are discussed.

PMID- 7731357
TI  - Ocular syphilis and neurosyphilis in a patient with human immunodeficiency virus
      infection.
AB  - A patient who presented with severely decreased bilateral vision was found to
      have syphilis and neurosyphilis that responded well to a 14-day course of
      penicillin and prednisone. The patient tested positive for HIV, which can alter
      the natural course of syphilis, often making the diagnosis and treatment
      difficult. Conventional therapy for syphilis may not be effective in patients
      with HIV. Any patient with syphilis who is in a high-risk group should be tested
      for HIV; conversely, any patient with HIV should be tested for syphilis if signs
      or suspicions exist.

PMID- 7731358
TI  - Brief report: chronic sinusitis management.

PMID- 7731359
TI  - Pertinent medical intelligence: accidental digital injection of epinephrine.

PMID- 7731360
TI  - Two types of representation in visual memory: evidence from the effects of
      stimulus contrast on image combination.
AB  - An imagery task was used to explore the distinction between visual memory
      representations that preserve surface features and more abstract descriptions.
      Subjects were shown two line drawings and were then asked to combine a visual
      image of each drawing in order to identify a novel figure. The main experimental
      manipulation concerned the contrast in which each drawing was shown, which was
      either normal or reversed. Experiment 1 showed that image combination was more
      efficient when the contrasts of the two drawings were congruent with each other,
      but only when the imagery task was performed under conditions emphasizing short
      term memory (STM). There was no effect of congruity when one of the images was
      generated from long-term memory (LTM). These results are consistent with the idea
      that the surface characteristics of a stimulus are preserved in visual STM, but a
      more abstract description is stored in visual LTM. In Experiment 2 we explored
      the influence of verbal recoding on performance of the imagery task by requiring
      subjects to suppress articulation. Under LTM conditions, performance of the
      imagery task was improved by suppression and became sensitive to contrast
      congruity. Under STM conditions, imagery was unaffected by suppression. Overall,
      these results support the distinction between surface and abstract descriptions
      in visual memory. However, they suggest that this distinction does not map onto
      that between STM and LTM in any simple way. It is suggested that short-term
      visual memory maintains surface descriptions and long-term visual memory
      preserves both surface and abstract descriptions. Verbal coding of visual stimuli
      appears to encourage the use of abstract visual descriptions.

PMID- 7731362
TI  - Matching words to concepts in two languages: a test of the concept mediation
      model of bilingual representation.
AB  - A categorization paradigm was used to investigate the relations between lexical
      and conceptual connections in bilingual memory. Fifty-one more fluent and less
      fluent English-French bilinguals viewed category names (e.g., vegetable) and then
      decided whether a target word (e.g., peas) was a member of that category. The
      category names and target words appeared in both English and French across
      experimental conditions. Because category matching requires access to conceptual
      memory, only relatively fluent bilinguals, who are able to directly access
      meaning for their second language, were expected to be able to use category
      information across languages. The performance of less-fluent bilinguals was
      expected to reflect reliance on lexical-level connections between languages,
      requiring translation of second-language words. The results provided evidence for
      concept mediation by more-fluent bilinguals, because categorization latencies
      were independent of the language of the category name. However, the performance
      of less-fluent bilinguals indicated that they did not follow a simple lexical
      translation strategy. Instead, these subjects were faster at categorizing words
      in both languages when the language of the category name matched the language of
      the target word, suggesting that they were able to access limited conceptual
      information from the second language. A model of the development of concept
      mediation during second language acquisition is described.

PMID- 7731361
TI  - Investigating the mixture and subdivision of perceptual and conceptual processing
      in Japanese memory tests.
AB  - The dual nature of the Japanese writing system was used to investigate two
      assumptions of the processing view of memory transfer: (1) that both perceptual
      and conceptual processing can contribute to the same memory test (mixture
      assumption) and (2) that both can be broken into more specific processes
      (subdivision assumption). Supporting the mixture assumption, a word fragment
      completion test based on ideographic kanji characters (kanji fragment completion
      test) was affected by both perceptual (hiragana/kanji script shift) and
      conceptual (levels-of-processing) study manipulations kanji fragments, because it
      did not occur with the use of meaningless hiragana fragments. The mixture
      assumption is also supported by an effect of study script on an implicit
      conceptual test (sentence completion), and the subdivision assumption is
      supported by a crossover dissociation between hiragana and kanji fragment
      completion as a function of study script.

PMID- 7731363
TI  - Transient phonemic codes and immunity to proactive interference.
AB  - Empirical data indicate that when memory for subspan lists of taxonomically
      related material is tested immediately after study, prior experience with lists
      involving the same material has no effect upon recall or recognition. In six
      experiments, we explored the possibility that immunity to proactive interference
      (PI) is related to discriminative information that is provided by transient
      phonemic codes. In these experiments, we manipulated the strength of phonemic
      codes as well as their presence or absence. Immunity to PI was found only when it
      was presumed that a phonemic representation of the target items existed and that
      information provided discriminative information. In all other cases, PI was
      observed. The finding that PI effects correspond with the manipulation of
      phonemic information in a principled fashion provides strong evidence for the
      role of phonemic codes in producing short-term PI effects.

PMID- 7731364
TI  - Organizational factors in the effect of irrelevant speech: the role of spatial
      location and timing.
AB  - Typically, hearing a repeated syllable produces minimal disruption of serial
      recall of visual lists, but a sequence of different syllables impairs performance
      markedly. Two conditions for presenting an identical sequence of three syllables
      are compared: one, in which, by means of stereophony, each syllable is assigned
      to the left, center, or right auditory locus (three streams not changing in
      state), and another, in which the same syllable sequence occurs in one location
      only (one stream with changing state). Disruption was significantly less in the
      stereophonic than in the monophonic condition. There was a joint effect of
      changing state and location, not an effect of the number of locations alone. In
      Experiment 2, temporal predictability was used to manipulate changing state. The
      disruptive effect of regular presentation of a repeated syllable was markedly
      increased when it was presented irregularly. The results are discussed in the
      context of organizational factors in short-term memory.

PMID- 7731365
TI  - The effect of repeated writing on memory.
AB  - Repeated writing, or rehearsal by writing, is a common memory strategy for the
      Japanese, especially when learning new logographic characters. The to-be
      remembered items are written down not as external prompts, as with reminder
      notes, but to be memorized in the course of writing them down over and over
      again. In this study, we investigated whether the strategy was effective, and if
      so, in which condition. Experiment 1 showed that repeated writing improved memory
      for graphic designs but not for Chinese characters, words, or syllables.
      Experiment 2 showed that the effect occurred for both Japanese and American
      subjects, suggesting that it was not the result of a cultural background
      associated with a logographic language. Instead, the effect seemed to be
      accounted for by the encoding specificity of visual-motor information, because
      repeated writing improved free recall--that included writing--but did not improve
      recognition (Experiment 3). In Experiment 4, the strategy was applied to learning
      the Arabic alphabet. Finally, similarities between repeated writing and Type 1
      rehearsal are discussed.

PMID- 7731366
TI  - When encoding fails: instructions, feedback, and registration without learning.
AB  - Four experiments replicated and extended the registration-without-learning
      effect, in which there is little improvement in the ability to discriminate an
      old target (X) from a highly similar test item (Y) after the first few
      presentations of X, even though judgments of frequency continue to rise in an
      open-ended fashion. Forced-choice testing revealed the anomalous form of the
      learning curve for X-Y discrimination (faster and then slower than the
      exponential). Effects of several different learning instructions were compared,
      but these appeared to affect only the level of initial learning, and to do little
      to promote X-Y discrimination learning on later presentations. The opportunity
      for self-testing with feedback during study provided no benefits when responding
      was covert, but did when overt anticipation was required. The findings are
      discussed in relation to the roles of bottom-up and top-down processing in memory
      encoding, and to the importance of error-correcting feedback in further
      structural learning of materials, once the materials have become familiar.

PMID- 7731367
TI  - Instance-based categorization: automatic versus intentional forms of retrieval.
AB  - Two experiments are reported which attempt to disentangle the relative
      contribution of intentional and automatic forms of retrieval to instance-based
      categorization. A financial decision-making task was used in which subjects had
      to decide whether a bank would approve loans for a series of applicants.
      Experiment 1 found that categorization was sensitive to instance-specific
      knowledge, even when subjects had practiced using a simple rule. L. L. Jacoby's
      (1991) process-dissociation procedure was adapted for use in Experiment 2 to
      infer the relative contribution of intentional and automatic retrieval processes
      to categorization decisions. The results provided (1) strong evidence that
      intentional retrieval processes influence categorization, and (2) some
      preliminary evidence suggesting that automatic retrieval processes may also
      contribute to categorization decisions.

PMID- 7731368
TI  - Use of prior beliefs in the assignment of causal roles: causal powers versus
      regularity-based accounts.
AB  - There is a tradition of models of causal judgment in which causes and other
      causal roles are defined and identified in terms of empirical patterns of
      association with effects. In the present experiments, results conflicting with
      the predictions of such models were obtained. In one experiment, subjects judged
      that an interpretation in which a factor constantly present was identified as the
      cause was more likely than was an interpretation in which a perfect positive
      covariate was identified as the cause. In a second experiment, possible effects
      of prior beliefs about covariation were controlled and similar findings were
      obtained in two out of three scenarios. These results favor the idea that people
      make causal judgments by applying preexisting beliefs framed in terms of causal
      concepts, such as causal powers, and in ways that cannot be accounted for by
      models in the empiricist tradition.

PMID- 7731369
TI  - Analogical transfer: from schematic pictures to problem solving.
AB  - A series of experiments was conducted to explore whether individuals can solve
      problems by transferring conceptual information gained from schematic pictures
      and to examine the mechanisms involved in this transfer process. Subjects viewed
      a schematic picture and then attempted to solve an insight problem to which the
      conceptual information from the picture could be applied. The results indicate
      that the degree of similarity--specifically, superficial and procedural
      similarity--between a source schematic picture and the target problem determined
      transfer performance. Discussion focuses on the relationship between these two
      types of similarity and the two key cognitive components involved in transferring
      pictorial analogies to solve problems: accessing the pictorial analogues and
      executing the solutions.

PMID- 7731370
TI  - Is the Safe Motherhood Initiative too ambitious?

PMID- 7731371
TI  - A factor analytic study of midwives' attitudes to research.
AB  - Midwives are increasingly being encouraged to undertake research activities at
      various levels, as a routine part of their job. However, despite topdown
      directives to this end, there is some evidence that relatively little research is
      published and reasons, such as lack of time, confidence and skill have been put
      forward to explain the short-fall. While these reasons may be valid obstacles, it
      is also conceivable that they are manifestations of a set of underlying attitudes
      to research in midwifery. If attitudes are assumed to be predictors of behaviour,
      then it may be relevant to study midwives' attitudes to research more closely in
      order to identify whether these are responsible in some measure for the short
      fall in research output. To this end, a national survey of 397 midwives was
      undertaken to establish their attitudes to research. The results were subjected
      to factor analysis, using an orthogonal solution, in order to establish whether
      any coherent source components existed in the sample's attitude responses. The
      factor analysis yielded four coherent factors, which were (i) other health care
      professionals' views of the value of midwifery research; (ii) the value of
      research for midwifery practice; (iii) the research role of the midwife; (iv)
      midwives' competence to carry out research. On further analysis the first two
      factors were also found to be significantly related to midwives' likelihood of
      undertaking research and publishing research findings. These factors could form
      the basis for future attitude change and staff development and training
      programmes as a means by which midwifery research output could be increased.

PMID- 7731372
TI  - Fetal monitoring--midwifery attitudes.
AB  - OBJECTIVE: to survey midwives' attitudes and practices related to intrapartum
      fetal monitoring. DESIGN: descriptive correlational study. SETTING: regional and
      district maternity unit and related community area within one health authority.
      PARTICIPANTS: all midwives were invited to participate. Two hundred and forty two
      questionnaires were administered and 117 were returned (48% response rate).
      MEASUREMENTS AND FINDINGS: in the questionnaire information was collected on
      professional/demographic details, education and practices related to intrapartum
      fetal monitoring, together with a 20-item attitude scale which encompassed
      attitudes towards fetal monitoring and related issues. As expected, the findings
      suggest that midwives' preferred methods of fetal monitoring varied with the
      client's risk category. However, midwife preference did not necessarily match
      actual choice of method. There are many factors influencing choice, not least of
      which is confidence in ability. Significant differences were found between
      midwives. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the findings highlight
      some of the issues relating to individual confidence. 97% of the midwives felt
      they would benefit from in-service training in CTG interpretation. The findings
      support the development of continuing in service education programmes for
      midwives.

PMID- 7731373
TI  - The effect of lateral asymmetries on breast feeding skills: can midwives' holding
      interventions overcome unilateral breast feeding problems.
AB  - OBJECTIVE: to determine whether the three human lateral asymmetrical behaviours
      (maternal handedness, maternal preferred cradling side, neonatal preferred head
      turning) affected the development of a unilateral breast feeding problem (UBP).
      DESIGN: quasi-experimental comparing 32 postnatal women who reported a UBP with
      28 who did not. SETTING: maternity unit in the south of England. PARTICIPANTS: 60
      mother/baby pairs where it was the mother's first attempt at breast feeding,
      there were no structural abnormalities of the breasts or nipples, no obstetric
      abnormalities, and where the mother had had no more than 100 mg pethidine in
      labour. The babies had to be less than 72 hours old at recruitment, show no
      abnormal behaviour, such as floppiness or irritability, and weighed 2500 g or
      more. MEASUREMENTS AND FINDINGS: handedness test, preferred cradling side
      established, neonatal preferred head turning established, demographic data. The
      two groups of women did not differ on demographic characteristics, but
      multiparous women were less likely to report a UBP or a neonatal preferred
      feeding side and more likely to be feeding at six weeks post delivery. Neither
      dominant handedness nor maternal preferred holding side alone were associated
      with a UBP but when the dominant hand was different from the preferred holding
      side, the women were more likely to have a problem side and to report a preferred
      feeding side. A neonatal head turning preference was associated with a UBP but
      not with success/failure of breast feeding at six weeks post-delivery. There were
      no associations between the holding interventions used by midwives and the
      successful continuation of breast feeding until six weeks post-delivery. KEY
      CONCLUSIONS: there is no conclusive evidence associating the management of a UBP
      with differing intervention holds. IMPLICATIONS FOR PRACTICE: there is a need of
      further research to select the most appropriate intervention to help an
      individual mother and baby.

PMID- 7731374
TI  - Community midwives' views and experience of home birth.
AB  - This two-part study explored the home birth experiences of all full time
      practising community midwives within three health authorities. The study
      consisted of a self-completion questionnaire, followed by interviews with a
      random stratified sub-sample of the midwives. The study sample consisted of 56
      midwives of whom 44 (78%) agreed to participate. The total experience of home
      birth by these midwives was limited. The mean number of home births undertaken in
      the previous year was only two and 14 midwives had not undertaken any. The
      average number of home births undertaken in their whole career was six. Four
      midwives (9%) had never undertaken any. Only two midwives (5%) routinely offered
      home birth at booking. Despite lack of experience, half the sample were strongly
      positive about home birth. Factors that influenced their feelings about home
      birth were more complex but were unrelated to the amount of their home birth
      experience, their age, training or own experience of childbirth. Positive
      feelings about home birth resulted from the quality of positive previous
      experiences, education and knowledge and an autonomous view of women and
      midwives. Negative feelings tended to result from a lack of specific skills,
      namely suturing, resuscitation and siting of IVIs, midwives' inadequate support
      networks, doctors' attitudes and a confused perception of the provision of
      emergency cover.

PMID- 7731376
TI  - Global Forum '94: from Rio to Manchester, UK.

PMID- 7731375
TI  - A study exploring midwives' education in, knowledge of and attitudes to nutrition
      in pregnancy.
AB  - OBJECTIVE: to explore midwives' education in, knowledge of and attitudes to
      nutrition in pregnancy. DESIGN: survey using questionnaire and interview
      schedule. PARTICIPANTS: a randomly selected sample of 77 Registered Midwives.
      SETTING: one English regional health authority. MEASUREMENTS AND FINDINGS:
      qualitative and quantitative data collection methods. Midwife teachers were
      responsible for 95% of teaching in nutrition. 86% of midwives had received no
      education in nutrition following qualification. 46% of midwives achieved a poor
      score in nutrition knowledge. Considerable numbers of midwives felt unprepared to
      offer dietary advice to women from ethnic minority groups (36%), vegetarians
      (66%) and to women with pre-existing medical conditions (41%). KEY CONCLUSION:
      midwives require more education in nutrition both during basic education and
      following qualification. IMPLICATIONS FOR EDUCATION PRACTICE: nutritional issues
      should be included in continuing education programmes available to qualified
      midwives.

PMID- 7731377
TI  - International Confederation of Midwives Africa region conference. 14-15 January
      1994.

PMID- 7731378
TI  - Endocrine effects in Asian postmenopausal women, treated with SH D 461 M and
      Prempak-C.
AB  - We reported the results of a randomized cross-over study comparing SH D 461 M
      (Climen) and Prempak-C in 38 postmenopausal women who were established users of
      hormone replacement therapy (HRT). Climen contains 11 tablets of 2 mg estradiol
      valerate (EV), and 10 tablets with 2 mg EV plus 1 mg of cyproterone acetate.
      Prempak-C, on the other hand, is a regimen consisting of 28 tablets of 0.625 mg
      conjugated equine estrogens (CEE); the last 12 tablets are taken together with
      0.15 mg of norgestrel (NG) tablets. Patients in Sequence I started with Climen
      for 6 months and then crossed-over to Prempak-C, for the next 6 months. Patients
      in Sequence II followed the reverse order. Following Climen treatment,
      significantly higher levels (P < 0.05, t-test) of sex hormone binding globulin
      (SHBG) and estradiol, when compared to Prempak-C treated subjects, were noted. No
      significant differences in follicle stimulating hormone (FSH), corticosteroid
      binding globulin (CBG), renin angiotensinogen, angiotensin-I and aldosterone
      levels between the two treatment regimens were noted. While both regimens were
      effective in reducing menopausal symptoms, none of the regimens could eliminate
      all symptoms completely. Treatment with Climen appeared to result in less
      frequent occurrences of some symptoms. During periods of no estrogen (only true
      for Climen) as well as periods of maximum P and E, subjects on Climen had
      significantly lower incidence of some of the symptoms (backache, lack of
      concentration, lethargy and swelling) when compared to those on Prempak
      C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731379
TI  - Oral contraceptive containing natural estradiol for premenopausal women.
AB  - An open multicenter trial was performed in six centers in Finland to study the
      efficacy, safety and acceptability of a new biphasic oral contraceptive pill
      containing natural estradiol and cyproterone acetate. The participants were 288
      women with a mean age of 39.3 +/- 3.4 years (range 30-49) who were willing to use
      the new pill as their only contraceptive method. In total, 23% of the women were
      smokers. The cumulative experience was 2800 treatment cycles during the first
      year. The net 12-month continuation rate was 63%. One pregnancy occurred in a
      woman who lost 5 tablets in the second treatment cycle, which gives a 12-month
      cumulative pregnancy rate of 0.4%. Serum progesterone values, determined twice
      during the third treatment cycle, showed ovulation inhibition in 95% of women.
      There were no serious side effects. Intermenstrual bleeding was recorded by 35.5%
      and 24.5% of women at 3 and 12 months, respectively. The bleedings became
      scantier in most women and dysmenorrhoea disappeared. No changes were observed in
      total and high density lipoprotein cholesterol concentrations after 1 year. With
      the exception of intermenstrual spotting, the efficacy, safety and acceptability
      of the new pill was almost as good as that of the modern low dose oral
      contraceptives. This is the first pill containing natural estradiol that has
      gained clinical acceptance and which can also be prescribed for smokers over 35
      years old until the climacteric.

PMID- 7731380
TI  - The climacteric among South-American women, who immigrated to Sweden and age
      matched Swedish women.
AB  - Forty-nine immigrated South-American (SA) and 48 Swedish women, aged 42-67 years,
      were studied in a comparative semi-structured interview survey, concerning the
      climacteric and its treatment. The mean age at natural menopause was 47 for the
      South-American women and 50 for the Swedish women. The prevalence of moderate to
      severe vasomotor symptoms at the time of the survey did not differ significantly
      between the non-treated, non-operated, postmenopausal South-American and Swedish
      women (36% and 21%; N.S.). One reason for the trend towards a higher prevalence
      among South-American women could be that a greater number of Swedish women used
      hormone replacement treatment compared to South-American women (11 vs. 4). The
      general attitude to hormone replacement therapy was more positive among South
      American women, although they did not use hormone therapy, as could be expected
      from their symptoms. These results are probably an illustration of the
      difficulties in getting access to treatment for the immigrated SA women.

PMID- 7731381
TI  - Low-dose 17 beta-oestradiol during maintenance therapy--a pharmacokinetic and
      pharmacodynamic study.
AB  - The vaginal absorption of oestradiol was studied during maintenance therapy with
      low-dose oestradiol. Six women with severe vaginal atrophy due to oestrogen
      deficiency were treated with a vaginal tablet containing 25 micrograms 17 beta
      oestradiol. Initially, a daily dose was given for 2 weeks, followed by
      maintenance therapy with twice weekly treatment for another 10 weeks. The plasma
      concentrations of unconjugated oestrone and oestradiol were measured before
      oestrogen treatment was started at the beginning of the study. After 3 months of
      treatment frequent plasma sampling over a period of 24 h was performed.
      Gonadotrophins, vaginal and urethral cytology, clinical findings and subjective
      symptoms were assessed at the beginning and end of the study. Plasma
      concentrations of unconjugated oestradiol were at all times within the limits of
      postmenopausal values, but showed a slight but not statistically significant
      elevation after 3 months compared to pretreatment values. Plasma concentrations
      of unconjugated oestrone were in the low postmenopausal range throughout the
      study. LH levels were unaffected during the study, while FSH was somewhat
      lowered, but still well within the postmenopausal range. Vaginal and urethral
      cytology showed maturation with almost complete disappearance of parabasal cells.
      Clinical and subjective improvement was statistically significant during the
      treatment period.

PMID- 7731382
TI  - Can progestin be limited to every third month only in postmenopausal women taking
      estrogen?
AB  - We evaluated whether a progestin, added for 14 days every 3 months to estrogen
      replacement therapy, is capable of preventing the development of endometrial
      hyperplasia in postmenopausal women during a treatment period of 2 years.
      Postmenopausal women (263) in 10 hospitals and medical centers in Finland
      participated in this non-randomized prospective multicenter trial. The women
      received estradiol valerate 2 mg daily for 84 days and 20 mg of
      medroxyprogesterone acetate daily for days 71-84 followed by seven drug-free
      tablets. This regimen was repeated four times per year. The first year of
      treatment was completed by 227 (86%) women and the second year by 143 out of 146
      women. The incidence of unscheduled and heavy bleedings was higher in women who
      were postmenopausal for less than 3 years. Endometrial biopsies demonstrated
      progestational response in 64% at 12 and 24 months, respectively. The 3 month
      regimen prevented development of endometrial hyperplasia but was not able to
      restore a hyperplastic endometrium to normal.

PMID- 7731383
TI  - Limited value of ultrasound measured skin thickness in predicting bone mineral
      density in peri- and postmenopausal women.
AB  - Measurement of skin thickness has been proposed to be capable of predicting low
      bone mineral density and the risk of osteoporosis in postmenopausal women. In
      order to investigate the association between the two factors, we measured skin
      thickness on the leg, lower abdomen and forearm by ultrasound scanning, and bone
      mineral density at the lumbar spine, femoral neck and distal radius by dual
      energy X-ray absorptiometry in 60 peri- and postmenopausal women. Only a loose
      association was found between skin thickness and bone mineral density at any
      site, the highest correlation being between lumbar bone mineral density and
      abdominal skin thickness. The results of our study confirm that there is some
      association between the two factors, but the measurement of skin thickness,
      although easy and reliable, is not a clinically sufficient method to predict bone
      mineral density.

PMID- 7731384
TI  - The vaginal epithelium in the postmenopause--cytology, histology and pH as
      methods of assessment.
AB  - In the study of postmenopausal vaginal oestrogen deficiency, an objective
      assessment of the vaginal epithelium is necessary. The present study was
      undertaken to evaluate different methods for assessing the vaginal epithelium,
      during atrophic and mature conditions. The vaginal epithelium was assessed by
      clinical examination, pH and vaginal cytology, including morphometric analysis,
      before and after oestrogen treatment. Biopsies of the vaginal wall were studied
      using descriptive histology and immunohistochemistry methods. The antigen Ki-67,
      a sensitive marker of cell proliferation, was detected using the monoclonal
      antibody MIB1. When comparing pre- and post-treatment values from the methods, a
      shift towards mature values was observed, but the magnitude of the shift differed
      to a considerable extent. Vaginal cytology, expressed as mean maturation index
      (MI) shifted significantly from 94/6/0 to 0/65/35. Likewise, mean pH was
      significantly shifted from 6.2 to mean 4.5. The increased presence of Ki-67
      positive cells could be demonstrated after oestrogen treatment, but the range of
      data was wide, which was also found for the thickness of the epithelium and the
      number of cell layers. For objective assessment of the vaginal epithelium
      maturation index and pH can be recommended.

PMID- 7731385
TI  - Forearm bone density and grip strength in women after menopause, with and without
      estrogen replacement therapy.
AB  - Peaking in young adulthood, both bone mass and muscle strength decrease with
      ageing, but bone loss may accelerate after the menopause and can be delayed by
      estrogen replacement therapy (ERT). This study was designed to evaluate whether,
      like bone density, the muscle strength was affected by the onset of menopause
      and/or ERT. First grip strength (GS) of young female adults (group III; n = 18;
      age (+/- S.E.M.) 21.8 +/- 0.4 years) was compared to that of postmenopausal
      women, who were divided into two groups. Group I (n = 22; age 59.6 +/- 1.6 years)
      was 12.5 +/- 1.7 years after the menopause and received no ERT, and group II (n =
      21; age 59.5 +/- 1.1 years) was 8.3 +/- 1.2 years after the menopause and had
      received ERT for 3.9 +/- 2.3 years at the time of the study. GS of the
      postmenopausal women was significantly (P < 0.005) lower than that of the young
      female adults. GS did not differ significantly between both postmenopausal
      groups. Further analysis revealed a weak negative correlation of years since
      menopause with forearm bone density (r = -0.37, P < or = 0.023 for group II and
      III together), but not with GS. It is concluded that the later onset of menopause
      and estrogen replacement therapy do not seem to have a noticeable influence on
      muscle strength.

PMID- 7731386
TI  - The impact of long-term testosterone replacement therapy on lipid and lipoprotein
      profiles in women.
AB  - The lipid and lipoprotein profiles of 39 female transsexuals, exposed to
      testosterone esters (250 mg monthly) for an average duration of 33 months after
      their sex reassignment operation (group 2), were compared to those of 29 normal
      menstruating female transsexuals prior to starting androgen therapy (group 1). A
      third group, comprising 17 post-operative female transsexuals were studied while
      on, and after stopping their androgen therapy for 6-12 months (group 3). The
      average concentration of testosterone in androgenized women was comparable to
      those found in normal males and levels of SHBG were significantly lower than
      those in the control group. No significant difference was noted between all
      levels of lipids and lipoproteins in pre-operative subjects of group 1 and
      corresponding levels in subjects of group 3 after they had stopped their androgen
      therapy for 6-12 months. Significantly higher levels of triglyceride (Trig),
      total cholesterol (TC), low-density lipoprotein (LDL-C) and apolipoprotein-B (Apo
      B) and a significantly lower level of high-density lipoprotein-cholesterol (HDL
      C) were noted in androgenized women (group 2) when compared to controls (group
      1). The two atherogenic indices, LDL-C/HDL-C and Apo-AI/Apo-B were significantly
      raised and lowered, respectively. Similar results were noted when comparing lipid
      and lipoprotein profiles in subjects of group 3 while they were on and after
      stopping their androgen therapy. Results from this study indicate that
      testosterone, per se, at supraphysiological doses may promote atherogenicity in
      women. Furthermore, the male predilection for coronary vascular diseases (CVD)
      may be due to the adverse effects of higher androgen levels on lipid and
      lipoprotein profiles.

PMID- 7731387
TI  - The climacteric, osteoporosis and hormone replacement; views of women aged 45-49.
AB  - We report climacteric symptoms among women aged 45-49, and their attitudes
      towards HRT and osteoporosis prevention. Semi-structured questionnaires were
      administered to 481 women attending for bone density screening after random
      invitation. We recorded social class, menopausal status, history of HRT exposure
      and climacteric symptoms, awareness of HRT and osteoporosis, and potential
      willingness to consider HRT before and after bone densitometry. In total, 294
      (61%) were from non-manual social classes; 338 (70%) were premenopausal, 68 (14%)
      postmenopausal and 75 (16%) uncertain; 101 (21%) were current/previous HRT users.
      Three or more climacteric symptoms were experienced by 189 (56%) of premenopausal
      women, compared to 64 (94%) of postmenopausal women. Most women had heard of HRT
      (96%) and osteoporosis (84%), usually from women's magazines or friends. HRT was
      usually prescribed for climacteric symptoms and, in one case, for osteoporosis
      prevention. Side effects were reported with most HRT preparations and affected
      38% of all users. Of the 380 (79%) women who had never taken HRT, half had
      concerns about such treatment, and few wanted it at the menopause. However, 364
      (96%) said they would consider HRT if their bone scan suggested increased
      osteoporosis risk. In conclusion, women around the menopause experience
      considerable climacteric morbidity, but are often anxious about HRT use. Better
      health education might improve HRT uptake, while long-term compliance might be
      enhanced by disclosure of fracture risk.

PMID- 7731388
TI  - Clinical experience with tibolone (Livial) over 8 years.
AB  - Tibolone (Livial), a synthetic steroid, relieves climacteric symptoms and
      maintains skeletal integrity in postmenopausal women. We have been using this
      compound for 8 years and have now reviewed our clinical experience in 301
      postmenopausal women. The majority (65.12%) had not previously received
      climacteric therapy; 34.55% had previously received oestrogen/progestogen
      therapy. A significant proportion of those started on tibolone were specifically
      referred for consideration of non-oestrogenic therapy because of a past history
      of breast dysfunction--27 women with benign breast disease and 11 women who had
      undergone surgery for carcinoma of the breast. Overall tibolone was well
      tolerated and climacteric symptoms were relieved within 3-5 weeks. The major side
      effect was weight gain and/or a tendency to bloating and oedema which occurred in
      11.28% of our women. Vaginal bleeding occurred in 33 women (12.69%) but in 17 of
      these women the bleeding was due to recent oestrogen therapy. Bleeding resulted
      from a polyp or fibroid in 11 women; no cause was found in the remaining five.
      Breast symptoms were reported by only 7.52% and no breast symptoms were reported
      in any of the 27 women referred because of benign breast disease. The total 'drop
      out-rate' due to side effects was only 2.66% (eight women).

PMID- 7731389
TI  - Yeast phylogenetic relationships based on cytochrome c sequences.
AB  - The availability of the KICYC1 sequence was used to establish homologies with
      other cytochrome c genes from yeasts and the fungus Neurospora crassa. In terms
      of nucleotide composition, the cytochrome c gene from Kluyveromyces lactis showed
      a higher homology with Schwanniomyces occidentalis than with Saccharomyces
      cerevisiae, and this point is discussed in regard to the differences found in the
      codon usage of these yeasts. The deduced amino acidic composition of the protein
      facilitated comparison of its sequence with other cytochrome c protein sequences
      and new assignments of phylogenetic relationships. In this context Kluyveromyces
      lactis was most closely related to Candida krusei.

PMID- 7731390
TI  - Characterization of resistance to essential oils in a strain of Pseudomonas
      aeruginosa (VR-6).
AB  - VR-6, a strain of Pseudomonas aeruginosa, harboured a plasmid and was not
      inhibited by 20 microliters ml-1 of essential oils (eucalyptus, lemongrass,
      palmarosa, and peppermint). On treatment with acridine orange, a clone VR-6-AO-1
      was obtained which was susceptible to 16.6 microliters ml-1 of eucalyptus or
      palmarosa oil. The plasmid DNA content of this clone was similar to the parent
      strain.

PMID- 7731391
TI  - Identification of the central regulatory segment of plasmid R6K complexed with
      the membranes of Escherichia coli.
AB  - Understanding the mechanisms which control replication of chromosomes with
      multiple origins of replication have been the subject of many investigations. The
      plasmid, R6K, has three origins of replication, alpha, beta, and gamma. In vivo,
      alpha and beta are utilized with equal frequencies while the gamma origin is
      rarely used in the parental plasmid, or remains silent in several miniplasmids.
      Hence, in the present study, the multiple origin plasmid, R6K, was utilized as a
      model system to investigate DNA replication. A 1.6 kb PCR (polymerase chain
      reaction) amplified region of R6K containing the central regulatory segment (CRS)
      was examined to determine if membrane complexing is required for maintenance.
      Crude membrane extracts from exponentially growing cultures were prepared and
      sedimented through 30-50% (w/v) linear sucrose gradients. Fractions collected
      were probed using quantitative PCR which revealed two fractions containing CRS
      DNA. These complexes were localized in a region between the inner and outer
      membranes of Escherichia coli.

PMID- 7731392
TI  - The structure of the tricellular region of endothelial tight junctions of
      pulmonary capillaries analyzed by freeze-fracture.
AB  - This study provides the first description of tight junction organization in the
      tricellular regions of pulmonary capillary endothelial cells. Three important
      characteristics of tight junction organization at these corners were observed.
      First, endothelial tight junctions are discontinuous at these corners where an
      intramembranous gap which averages 27.4 +/- 2.3 (SE) nm in width and 1.1 + 0.17
      (SE) micron in length was observed to cross the depth of the junctional complex
      and endothelium. Second, the depth of the tricellular region of endothelial tight
      junctions at these corners was made possible by an overlapping flap provided by
      one of the three cells, the flap cell, which covers the remaining two adjacent
      cells. Third, the observations in this study demonstrated that the tricellular
      regions of endothelial tight junctions are oriented parallel to the plane of the
      endothelium rather than perpendicular as in epithelium. A model of this
      organization, based upon freeze-fracture replicas of 16 tricellular regions, thin
      section data, and scanning electron microscopic data of perfusion fixed guinea
      pig lungs is provided.

PMID- 7731393
TI  - Regional changes in the extravasation of albumin in the canine kidney: comparison
      of bradykinin and water diuresis.
AB  - This report describes the adaptation of the albumin bound Evans blue dye (EB)
      extraction technique and its use in identifying regional changes in albumin
      extravasation rates. We present data to justify our technical approach and
      highlight the use of this method by describing differences resulting from two
      different models of induced diuresis and natriuresis. Results observed under
      control conditions (Group 1) are compared to those obtained following the
      infusion of bradykinin (BK) into the left kidney (Group 2) or hypotonic saline
      induced water diuresis (Group 3). EB and water content of tissue samples of
      cortex (CTX), outer medulla (OM), inner medulla (IM), and papilla (PAP) regions
      are reported. Under control conditions a significant heterogeneous distribution
      of EB and water content (wet/dry tissue weight) between zones was observed. Left
      kidney EB values for the CTX, OM, IM, and PAP in Group 1 were 125 +/- 11, 398 +/-
      56, 763 +/- 51, and 741 +/- 52 micrograms EB/g dry tissue and respective wet/dry
      tissue ratios were 4.48 +/- 0.05, 5.10 +/- 0.19, 7.13 +/- 0.37, and 6.35 +/-
      0.32. In Group 2, BK caused a selective increase in cortex EB content to 201 +/-
      7 (P < 0.01) micrograms EB/g dry tissue, without altering water content values.
      Results of EB extraction in Group 3 revealed no change in the CTX but significant
      increases in the OM, IM, and PAP regions: 576 +/- 40 (P < 0.01), 910 +/- 60 (P <
      0.01), and 850 +/- 69 (P < 0.05) micrograms EB/g dry tissue, respectively.
      Likewise, tissue water content values were unchanged in the CTX but significantly
      greater in the OM, IM, and PAP: 6.02 +/- 0.22, 8.90 +/- 0.25, and 8.40 +/- 0.17,
      respectively (P < 0.01, all three values). This technique clearly shows the
      regional heterogeneity of the renal microvascular network and allows the
      localization of intrarenal changes in albumin extravasation. This method provides
      evidence that BK increases albumin extravasation in the cortex only and that
      changes in the renal medulla are obtained in hypotonic saline-induced water
      diuresis.

PMID- 7731394
TI  - Renal reperfusion injury: sequential changes in function and regional albumin
      extravasation.
AB  - We report on the renal function and regional extravasation of albumin-bound Evans
      blue dye (EB) in the kidneys of anesthetized dogs following 30 min occlusion of
      the left renal artery. Left kidney (LK) function was halted and no change in
      right kidney (RK) function was observed during ischemia. Clearances of para-amino
      hippurate and inulin from the LK were significantly (P < 0.01) less than control
      after 10 min of reperfusion, 22.6 +/- 6.8 vs 90.1 +/- 7.8 and 9.0 +/- 2.9 vs 34.2
      +/- 2.1 ml/min, respectively. Renal hemodynamic parameters never did fully
      recover in subsequent periods but filtration fraction was unchanged from control
      throughout the reperfusion period. Urine flow and sodium excretion from the LK
      was significantly (P < 0.01) less than control values after 10 min of
      reperfusion, 0.41 +/- 0.14 vs 0.80 +/- 0.08 ml/min and 60 +/- 21 vs 161 +/- 8 mu
      eq/min, respectively, but fully recovered in subsequent periods. Significant (P <
      0.01) decrease from control values in the LK content of EB was observed in the
      inner medulla and papilla regions after 30 min of reperfusion, 586 +/- 60 vs 763
      +/- 51 and 549 +/- 54 vs 741 +/- 52 micrograms/EB/g dry tissue, respectively.
      After 60 min of reperfusion in the LK, significant (P < 0.05) changes from
      control in EB content were evident exclusively in the outer medulla, increasing
      from 398 +/- 56 to 491 +/- 17 micrograms/EB/g dry tissue, respectively. A general
      edema in the LK, measured as an increase in the ratio of wet/dry tissue weight,
      became evident only after 60 min of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731395
TI  - Effects of aging and hypertension on the reactivity of isolated conduit and
      resistance vessels.
AB  - We have studied the effects of hypertension and aging on the concentration
      response curves for alpha 1-adrenoceptor-mediated vasoconstriction and
      methacholine-induced endothelium-dependent relaxation. The experiments were
      performed in aortic rings and in perfused mesenteric vascular bed preparations
      taken from WKY rats, from SHR of 16-18, 28-30, and 58-60 weeks, and from 16- to
      18-week-old SHRSP rats, respectively. The influence of aging and/or hypertension
      caused no alterations of the alpha 1-agonist response provoked by phenylephrine
      in aortic rings. Mesenteric vascular bed preparations showed an increase in
      maximal response to methoxamine when taken from hypertensive animals. Age per se
      did not change the contraction in the mesenteric arteries. Hypertension in
      combination with age caused a decrease in endothelium-dependent vasodilation
      induced by methacholine in aortic rings, but not in mesenteric arteries. However,
      the sensitivity to methacholine decreased age-dependently in the mesenteric
      vascular bed preparation taken from the WKY and SHR. The endothelium-independent
      relaxation induced by sodium nitroprusside showed a decrease in sensitivity in
      aortic rings taken from 58- to 60-week-old SHR when compared with the age-matched
      WKY. These findings suggest that the mechanisms beyond the endothelium involved
      in vasodilation are not responsible for the decreased methacholine-induced
      relaxation in aortic rings. It is concluded that (1) the responsiveness of
      resistance arteries to adrenoceptor stimulation only changes with elevated blood
      pressure and (2) hypertension in combination with aging induces an endothelial
      dysfunction in conduit arteries but not in resistance vessels.

PMID- 7731396
TI  - Evaluation of pulsatile and nonpulsatile flow in capillaries of goat skeletal
      muscle using intravital microscopy.
AB  - It is commonly believed that pulsatile flow generated by the pumping action of
      the heart is dampened out by the time it reaches the microcirculation. In
      clinical practice, most of the cardiopulmonary bypass pumps and ventricular
      assist devices are nonpulsatile. To test the hypothesis that pulsatile flow
      generated by the heart does exist at the microvascular level, intravital
      microscopy of a large animal model (goat) was developed to visualize and to
      videorecord the surface microcirculation of the flexor carpi ulnaris muscle from
      the right forelimb. Density of perfused capillaries and red blood cell velocity
      in capillaries were measured in five goats during pulsatile perfusion provided by
      the heart and during a subsequent 3-hr period of nonpulsatile perfusion provided
      by a centrifugal ventricular assist device (Centrimed, Sarns 3M) that bypassed
      the heart. Throughout the experiment, the heart rate, innominate artery mean
      blood pressure, and flow remained unchanged. During the pulsatile regimen,
      velocities showed regular fluctuations that coincided with the period of the
      cardiac cycle (range of periods: 0.5-0.8 sec). The peak velocity amplitudes
      (range: 0.25-0.55 mm/sec) correlated directly with the amplitude of the pulse
      pressure. During the nonpulsatile regimen, no such correlations were seen. During
      pulsatile flow and during the 3-hr nonpulsatile period, capillary density
      remained stable at 24 capillaries/mm of test line but there were significant
      increases in red cell velocity, from 0.8 to 1.2 mm/sec (P < 0.05), and in
      coefficient of variation of velocity (used as an index of flow heterogeneity),
      from 19 to 34% (P < 0.05). We conclude that (1) pulsatility exists in the
      capillary bed and that it directly correlates with the pumping action of the
      heart and (2) nonpulsatile flow produced by the ventricular assist device does
      not cause an acute deterioration in microvascular perfusion. We interpret the
      increase in heterogeneity of flow as an early sign of microvascular dysfunction.
      Prolonged use of the nonpulsatile device may, therefore, lead to deterioration in
      perfusion that could compromize the function of the organ.

PMID- 7731397
TI  - Endothelial wounds with disruption in cell migration repair primarily by cell
      proliferation.
AB  - Disruption of vascular integrity results in activation of endothelial cells to
      initiate repair. Cytoskeletal reorganization, cell spreading, migration, and
      proliferation are important processes which regulate rapid and efficient repair.
      Cell proliferation has been thought to be a secondary event and dependent to a
      large extent on prior cell migration. We used a model of dysfunctional repair to
      test the hypothesis that a reduction in migration will result in a reduction in
      cell proliferation. The extent of cell proliferation was studied in an in vitro
      repair model, in which endothelial function is studied during the closure of a
      1500-microns mechanically induced wound in a confluent monolayer. Dysfunctional
      repair is induced in this model by transiently inhibiting endothelial cell
      transcription. Wounds are incubated with actinomycin D at the time of wounding
      for 2 hr, which results in wound closure taking about 4.5 times longer than
      normal. Cell proliferation is measured by 5-bromo-2'-deoxyuridine incorporation.
      In actinomycin D-treated wounds, the rate of cell migration is reduced, and for
      the first 120 hr very little cell proliferation occurs and it involves the first
      4 rows of cells adjacent to the wound edge. This is in comparison to normal
      wounds in which proliferation is prominent by 24 hr after wounding, also
      involving the first 4 rows of cells and by 48 hr, proliferation extends to
      involve the first 10 rows of cells. In dysfunctional wounds, however, it takes
      144 hr after wounding before the first 10 rows of cells begin to actively
      proliferate. In addition, proliferation occurs deeper in the monolayer and this
      level is maintained over the next 144 hr, when the wound closes. Thus, when
      migration is reduced, proliferation becomes prominent and persists to complete
      repair. However, the overall rate of repair is reduced.

PMID- 7731398
TI  - Standard and near-surface laser-Doppler perfusion in foot dorsum skin of diabetic
      and nondiabetic subjects with and without coexisting peripheral arterial disease.
AB  - Appropriate assessment of microvascular function is now recognized as an
      important adjunct to the diagnostic workup and medical follow-up for a variety of
      conditions. Laser Doppler fluxmetry (LDF)-derived rbc perfusion (Q) and the
      volume (V) and velocity (U) components are useful in this regard but the fact
      that the sampled volume includes both nutritional and nonnutritional components
      may limit its specificity and range of usefulness. It was reasoned that if the
      depth of penetration could be reduced without significantly altering essential
      optical transmission features, then the detected signal would better represent
      the nutritional component. A 0.68-mm-thick Delrin spacer was fabricated and used
      to compare LDF values with (WITH) and without (WITHOUT) its use on the foot
      dorsum of 71 limbs of 44 diabetic (DM) and nondiabetic (NO-DM) subjects with
      lower extremity arterial disease (LEAD, n = 39) and without disease (NORM, n =
      32). Overall LDF values WITH as compared to WITHOUT had a slightly greater U
      (1.01 vs 0.89 mm/sec, P < 0.01) and much lower V (0.06 vs 0.63%, P < 0.001) and Q
      (0.25 vs 1.88 ml/min/100 g, P < 0.001). In NO-DM subjects, WITH detected a lower
      Q in limbs with LEAD (0.14 vs 0.27, P < 0.05) but WITHOUT did not (1.48 vs 1.47,
      ns). In DM subjects, WITH measured a significantly lower U in LEAD limbs (1.05 vs
      1.22 mm/sec, P < 0.05), which was not detected WITHOUT. Without the spacer, NORM
      limb LDF values were all greater in DM vs NO-DM subjects. With spacer use, only
      the DM velocity component was significantly greater. Use of a modified LDF
      procedure has shown both utility and promise as a method for evaluation of skin
      microcirculation and appears to offer some potential benefits as compared with
      the currently used standard method. Previously undocumented differences between
      LEAD and NORM limbs in DM and NO-DM patients as herein reported represent initial
      findings using a 0.68-mm spacer.

PMID- 7731399
TI  - A theoretical model for gas transport and acid/base regulation by blood flowing
      in microvessels.
AB  - An investigation was made of the coupling between O2 and CO2 transport by blood
      flowing in microvessels. The blood was treated as two continuous coexisting
      phases: a red blood cell (RBC) phase and a plasma phase. The microvessel was
      divided into two regions: the central, RBC-rich and the outer, cell-free region.
      The radial distribution of RBCs and transport of various species due to bulk
      convection and radial diffusion were taken into account. Chemical and transport
      processes which were included in the model are (1) interactions of hemoglobin
      with O2 and CO2, (2) the Bohr and Haldane effects (the inter-dependence of O2/CO2
      transport), (3) CO2 hydration-dehydration reactions, (4) buffering actions of
      hemoglobin and plasma proteins, and (5) anion exchange across the red cell
      membrane. The governing equations of the model subjected to the imposed inlet and
      boundary conditions were solved numerically to provide the concentration
      distributions of various species in blood that are important in the simultaneous
      gas exchange and pH regulation process. Predictions of the new model of
      simultaneous O2/CO2 transport by flowing blood were shown to be in excellent
      agreement with prior workers' experimental results from large artificial membrane
      tubes. A previous mathematical model which treats blood as a homogeneous
      continuum and uses a local chemical equilibrium approximation to describe the gas
      transport was shown to satisfactorily predict the amount of O2 transport for
      blood oxygenation accompanied by CO2 elimination. However, the previous model
      significantly underpredicts O2 transfer for blood deoxygenation accompanied by
      CO2 uptake. Furthermore, the previous model disagrees substantially with the CO2
      transport results under both oxygenation and deoxygenation conditions.

PMID- 7731400
TI  - Tissue-isolated human tumor xenografts in athymic nude mice.
AB  - An ex vivo perfused solid tumor preparation provides control over the
      physiological, biochemical, and pharmacological composition of the arterial input
      and easy access to the venous output. This is advantageous for studies of
      transport and metabolism in solid tumors. Here we present a tissue-isolated tumor
      preparation adapted to the nude mouse, allowing ex vivo perfusion of human tumor
      xenografts. Previously, such preparations have only been developed in rats, to
      study primarily rodent tumors. In the present study this new tumor preparation is
      physiologically characterized in comparison with subcutaneously transplanted
      tumors in nude mice using the human colon adenocarcinoma LS174T.

PMID- 7731401
TI  - A holder and calibration chamber for micropressure measurements.

PMID- 7731402
TI  - Pain management: implementation of AHCPR guidelines.

PMID- 7731403
TI  - Workplace changes affect nurses.

PMID- 7731404
TI  - [Carcinogenic risk of extremely-low-frequency electromagnetic fields: state of
      the art].
AB  - This paper summarizes the published literature and current problems relating to
      possible cancerogenic effects of occupational and residential exposure to ELF
      electromagnetic fields at levels slightly above ambient background. There are
      several suggestions that such an exposure may increase the risk of cancer, but
      these studies failed to provide conclusive indications. The present state of
      uncertainty led to a variety of recommendations and statements being made
      concerning restrictions to the exposure of people to ELF electromagnetic fields.
      Attempts to detect direct chromosomal damage from ELF electromagnetic fields have
      proven negative, while results on cancer promotion have been controversial. On
      the basis of several epidemiological studies on occupational exposure, an
      increased risk of leukemia, brain cancer and male breast cancer is apparent; the
      literature on residential exposure provides some evidence of an effect on
      childhood cancer, especially leukemia; however, when interpreting these results
      some major methodological concerns should be kept in mind. In conclusion, the
      public concern and potential public health impact of this environmental agent
      argue strongly for addressing further research in order to identify mechanisms of
      action on biological systems, to define the proper assessment of exposure and to
      obtain good epidemiological evidence.

PMID- 7731405
TI  - [Hand-arm vibration syndrome: diagnostic aspects, dose-response relationship and
      exposure limits].
AB  - This paper reviews the clinical aspects and laboratory methods to diagnose the
      vascular, sensorial and neural components of the hand-arm vibration syndrome. The
      resolutions adopted by the experts of the Stockholm Workshop 94 are reported. The
      methods of measurement and assessment of both daily and cumulative vibration
      exposure are discussed with respect to the risk for vibration-induced disorders
      of the upper extremities. An update of the relationship between vibration
      exposure and the occurrence of vibration-induced white finger (VWF) is given, as
      well as the results of epidemiologic studies of the reversibility of VWF after
      cessation of vibration exposure or introduction of vibration isolation systems in
      forest work. Regarding occupational exposure to hand-transmitted vibrations, this
      review considers the guidelines and provisions contained in the European
      Communities (EC) Directive for machinery (89/393/EC) and the proposal for an EC
      Directive for physical agents (94/C 230/03).

PMID- 7731406
TI  - Tunnel syndromes of the upper extremities in workers using hand-operated
      vibrating tools.
AB  - Neurological and electrophysiological (EMG, ENG) examinations of the upper
      extremities were carried out in 167 patients exposed to hand-arm vibrations. All
      patients had typical symptoms (Raynaud's phenomenon and/or numbness, muscle
      weakness). The results showed that the circumscribed lesions of the tunnel nerves
      are far more common (92.8%) than diffuse peripheral neuropathies (22.7%). The
      most common alteration (71.4% below the border-line values) was the lesion of the
      brachial plexus in the thoracic outlet. In 16.2% of the patients compression of
      the subclavian artery was also demonstrated by means of a Doppler flowmeter.
      Cubital tunnel syndrome was observed in 42.5% of the patients. The results
      suggest that hand-arm vibration can play a part in the development of the
      thoracic outlet and cubital tunnel syndromes. On the other hand the thoracic
      outlet syndrome can contribute to the development of vibration-induced Raynaud's
      phenomenon.

PMID- 7731407
TI  - [Mucociliary clearance and respiratory function in foundry workers].
AB  - The aim of the study was to establish whether changes occur in respiratory
      function, particularly mucociliary clearance, among second fusion smeltery
      workers. The research covered 93 male smelters employed in steel forming and
      casting and 116 male workers of an electric power station, considered as non
      exposed. Physiological, pathological and occupational histories of all subjects
      under study were available. An ECCS respiratory symptoms questionnaire was
      administered to all subjects ad the two groups also underwent a general medical
      examination, a spirometry and a chest X-ray. During the medical examination
      sputum was collected from the subjects to measure mucus transport rate on frog
      palate, expressed as Normalised Frog Palate Transport Rate (NFPTR). For the
      environmental research, dust, fumes and gas samplings were taken either at a
      fixed station or by means of personal dosimeters. Environmental research revealed
      very low concentrations of respiratory irritants (total dust: 0.2-6.8 mg/m3;
      respirable dust: 0.1-4.9 mg/m3; total silica: < 2-15.5%; respirable silica: <
      0.004-0.3 mg/m3; iron: 0.008-0.085 mg/m3; chromium and manganese: < 0.001 mg/m3;
      fumes and gases: well below the TLV. The two groups were homogeneous with regard
      to age and smoking habits. Exposed workers showed rales, dyspnoea and spontaneous
      phlegm more frequently than non-exposed workers. NFPTR alterations were checked
      in 49 out of 81 exposed and in 18 out of 81 non-exposed subjects (chi squared =
      22.9; p < 0.001). Stratification of the results according to smoking habits
      further confirmed the strong association between occupational exposure and NFPTR
      alterations. Smelters showed significantly lower mean NFPTR values compared to
      non-exposed subjects; also, the mean value of NFPTR in the exposed was below
      0.70, which is considered the lowest individual limit in normal subjects. The
      only variable which explains a large part of the variability of NFPTR is past
      work in a smeltery rather than in an electric power station. The spirometries
      showed that only the mean PEF values were significantly lower among the exposed.
      Stratified analysis of the results according to smoking habits in the two groups
      revealed a close association between smeltery work and reduction of PEF to under
      80% of the ECCS 1983 theoretical values, independently of smoking habits. We also
      compared the mean PEF values, both as measured values and as percent values of
      the ECCS 1983 theoretical values, stratified for occupational exposure and
      smoking; the results again showed that differences between these mean values were
      mainly due to current or past work in the foundry.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7731408
TI  - [Scleroderma and occupational factors: a case-control study and analysis of
      literature].
AB  - The scientific literature concerning occupational factors associated with
      scleroderma consists mostly of case report type studies. We therefore undertook a
      case-control study in the Province of Trento using as data source the Hospital
      Records System. The annual rate of scleroderma incidence in the period considered
      (1976-1991) was 5.8 per million in females and 1.5 per million in males. A
      statistically significant association was observed (OR = 9.28, p = 0.039) in the
      population under study for occupational exposure to solvents. Also, an excess
      risk was observed in male subjects exposed to silica dust, even though the
      simultaneous exposure to other risk factors, such as hand-arm vibrations, makes
      it difficult to establish the specific contribution of silica dust exposure.

PMID- 7731409
TI  - [Lead poisoning caused by stonework treatment in architectural restoration].
AB  - An unexpected lead exposure occurred among a team of masons employed in
      restoration work of the facade of an 18th century church in Vicenza, Italy. The
      unusual case of lead intoxication (PbB up to 71 micrograms/dL, PbU-EDTA 8636
      micrograms/24 h after the first 1 g dose of Na2Ca EDTA) in a mason suffering from
      abdominal pain was reported to our unit by the local General Hospital. An
      investigation on the possible sources was therefore set up and the source was
      identified in the removal of an old paint made of white lead (basic lead
      carbonate) from the statues and decorative stonework of the church. An extension
      of the investigation confirmed that many sculptures and stonework from the same
      period, especially in religious buildings, were treated in the same way. The
      biological exposure indices of the subject's work fellows also confirmed an
      abnormal lead absorption. The occupational risks involved in various methods in
      restoration crafts are evaluated and preventive measures are suggested.

PMID- 7731410
TI  - [Exposure to glues containing technical heptane: a clinical and
      electrophysiological study].
AB  - Polyneuropathy caused by n-hexane contained in glues was, until recently, the
      typical occupational disease of shoemakers. Glues no longer contain large
      concentrations of this solvent, and in some cases, it as been completely replaced
      by other hydrocarbons. The authors investigated the health status in a group of
      shoemakers using glues containing 35% technical heptane. The same glue, not
      containing n-hexane, was used by a shoemaker who worked at home; she developed an
      otherwise unexplainable peripheral polyneuropathy. For each of the 16 subjects,
      the following procedures were carried out: environmental sampling, biological
      monitoring for Mek and heptane metabolites, a neurological and electromyographic
      examination. No neurological abnormalities were found in the workers that could
      be attributable to occupational exposure, probably due to the low level
      environmental contamination (< 100 mg/m3 n-heptane) found in the 7 factories and
      workshops studied where acceptable hygiene conditions existed. The time course
      and ratio of urinary metabolites of heptane were also studied, the latter showing
      a predominance of 2- and 3- heptanol in the initial phase and 2-5 heptandione at
      the end of the work week; probably, the presence of other solvents, such as Mek,
      can modify the ratio of metabolites and consequently the formation of neurotoxic
      compounds could result.

PMID- 7731411
TI  - Reproductive function in men following exposure to chemical warfare with sulphur
      mustard.
AB  - To investigate the acute and chronic effects in young men of exposure to chemical
      warfare containing mustards, the time course of changes in serum concentrations
      of total and free testosterone, dehydroepiandrosterone (DS), follicle-stimulating
      hormone (FSH), luteinizing hormone (LH) and prolactin was evaluated in 16 men in
      the first three months and testicular function in 42 men one to three years after
      injury. Serum total and free testosterone and DS were markedly decreased in the
      first five weeks after exposure. The lowest values were: total testosterone 237
      +/- 165, free testosterone 22.5 +/- 9.7, DS 39 +/- 25; as compared to controls:
      total testosterone 773 +/- 245 ng/dl, free testosterone 35.5 +/- 11.2 pg/ml and
      DS 207 +/- 37 micrograms/dl. FSH, LH, prolactin and 17 alpha-OH progesterone were
      normal in the first week. The response to GnRH was subnormal in four of five
      subjects. LH increased by the third and FSH and prolactin by the fifth week. All
      hormone levels had returned to normal by twelfth week after exposure. In 28 of 42
      men seen one to three years following injury, sperm count was below 30 million
      cells/ml, and FSH was increased as compared to men with sperm above 60 million
      cells/ml. Testicular biopsy showed complete or relative arrest of
      spermatogenesis. This study demonstrates that the exposure to sulphur mustard
      results in very low androgen levels and hypo-responsiveness to GnRH in the first
      five weeks and normalization by the twelfth week after injury. However, side
      effects of mustard on sperm cells persist and may cause defective spermatogenesis
      years after exposure.

PMID- 7731412
TI  - Reviewing Frankl's Will to meaning and its implications for psychotherapy dealing
      with post-traumatic stress disorder.
AB  - Recent research has shown that people who have gone through war experiences in
      one way or the other tend to manifest reactions classified as post-traumatic
      stress disorder. Viktor Frankl, the founder of logotherapy, manifested PTSD
      reactions when he was in a concentration camp. This paper attempts to sketch how
      he lived through his traumatic experiences by relying on the principle of Will to
      Meaning as his survival mechanism. Two implications will be outlined derived from
      this principle for psychotherapies dealing with disaster survivors.

PMID- 7731413
TI  - [Acute lymphoblastic leukemia in children].

PMID- 7731414
TI  - Food allergy in cystic fibrosis.
AB  - Food allergy was investigated in 20 children with cystic fibrosis (CF), who still
      suffered from diarrhea and failed to thrive, in spite of adequate diet and enzyme
      treatment (group A). The study also included two age-matched control groups,
      comprising 10 CF children without intestinal symptoms and/or failure to thrive
      (group B), and 20 healthy children (group C). Skin tests were positive and total
      IgE higher than the mean + 2SD respectively in 14/20 and 11/20 patients of group
      A, in 3/10 and 2/10 patients in group B and in none in group C. The specific IgE
      were present in 6/14 children in group A whose skin tests were positive and in
      none in group B. There was no significant difference between group A and group B
      (p > 0.05). The levels of specific antibodies IgG, IgA and IgM were overall
      higher than the mean + 2SD of the normal in 18/20 in group A, in 6/10 in group B
      and in none in group C. The measurement by ELISA of specific antibodies for cow
      milk and egg proteins showed a statistically significant difference for casein,
      beta-lactoglobulin and ovalbumin between the IgG (p < 0.05) and IgA (p < 0.001)
      levels in group A and the other groups (B and C). Symptoms improved in 90% of CF
      patients (group A) when the implicated foods were eliminated from the diet and in
      78% the oral provocation test resulted positive. The occurrence of food allergy
      must be considered in CF patients who do not improve with the conventional
      treatment. In these patients immunological investigations, in particular the
      measurement of IgG, IgA and IgM specific antibodies, are useful for diagnosis and
      in selecting an appropriate diet leading to an improvement in nutritional status.

PMID- 7731415
TI  - [Influence of the early mother-infant contact in the delivery room on short or
      long term breast feeding].
AB  - Two groups of mothers and their children were followed up in order to assess the
      influence of early mother-child contact on breast-feeding; a first control was
      carried out at discharge from the nursery and a follow-up 6 months later. All the
      mothers were in good health and pregnancy was physiological with uncomplicated
      eutocic delivery; none of the babies presented pathologies during the period of
      their stay in the nursery and in the subsequent 6 months. Group A comprised 126
      mothers who had had contact with their babies in the delivery room for at least
      one hour; group B comprised 109 mothers whose first contact with their baby was
      only 3-6 hours after birth. Significant differences between the 2 groups were
      observed as early as the first control which took place at discharge from the
      nursery: 69.1% of the babies in group A against 51.3% in group B had taken
      mother's milk exclusively (p < 0.01). Equally significant differences emerged
      from the subsequent control at 6 months: 70 babies out of 116 (60.4%) were breast
      fed exclusively or partially, against 42 out of 101 (42.4%) in group B (p <
      0.01). Furthermore, important data emerged from the duration of breast-feeding,
      whether this was exclusive or otherwise, in the first 6 months of life: group A
      differed significantly from group B (p < 0.002). Our figures suggest a positive
      influence of early mother-child contact on breast-feeding and on its duration.
      Notwithstanding the fact that there is no unanimous confirmation in the
      literature, it is considered that such behaviour will bring benefits to both
      mother and child.

PMID- 7731416
TI  - [Efficacy of magnesium in a case of neonatal pulmonary hypertension refractory to
      the usual therapies].
AB  - We describe a premature baby with X pentasomy, having a severe pulmonary
      hypertension secondary to perinatal asphyxia and hyaline membrane disease which
      appeared to be refractory to conventional treatments (hyperventilation,
      tolazoline, prostacyclin). Oxygenation and pulmonary hypertension rapidly
      improved after starting magnesium sulphate infusion (loading dose: 20 mg/kg e.v.
      of elementary Mg, followed by continuous infusion of 2-4 mg/kg/hr during 6 days).
      The therapy was associated with hypermagnesemia (5-7 mg/100 ml) and transitory
      side effects (hypocalcemia, muscular and bladder paresis, bradycardia without
      hemodynamic decompensation). We suggest that magnesium therapy might be
      considered in newborns with severe and persistent pulmonary hypertension.

PMID- 7731417
TI  - [Drug-induced interstitial nephritis. A case report].
AB  - Most instance of drug-induced renal disease are probably due to direct toxicity;
      the most common immunologically mediated lesion of the kidney due to drugs
      appears to be interstitial nephritis-fever, skin rash, eosinophilia,
      eosinophiluria frequently accompany the renal symptoms. One case we report due to
      ceftriaxone; the disease subsided completely when the treatment with the drug has
      been stopped.

PMID- 7731418
TI  - [Posterior cranial fossa hemorrhage in term newborn infants: clinical and
      ultrasonographic aspects in 2 cases].
AB  - Haemorrhages of the posterior cranial fossa were diagnosed by cerebral
      sonography, sometimes these lesions were misinterpreted by the examination. We
      report two cases of posterior fossa haemorrhages in the term newborn without
      ultrasonography signs of this pathology. In a case some days after haemorrhagical
      damage, the signs of past haemorrhage were demonstrated.

PMID- 7731419
TI  - [A case of organic psychosis in dermatomyositis. Etiopathogenetic hypothesis].
AB  - The authors describe a girl affected by dermatomyositis, with a quick and grave
      evolution, which required urgent tracheostomy to reduce the dysphagic symptoms.
      During the observation the patient showed psychotic symptoms. After the revision
      of literature, in which no such complication has ever been described, the authors
      propose an etiopathogenetic interpretation for a generalized acute psycho-organic
      syndrome, supposing a cerebral hypoxic damage, as vasculitic manifestation,
      probably complicated by symptoms of hysterical conversion, due to the isolation
      of the patient in the Department of Intensive Therapy and to the severe physical
      conditions.

PMID- 7731420
TI  - [Hydrogen breath test in celiac disease: relationship to histological changes in
      jejunal mucosa].
AB  - Hydrogen concentration in expired breath depends on the fraction of ingested
      carbohydrates unabsorbed by the small intestinal mucosa which reach the large
      intestine and are fermented by the colonic flora. The aim of this study is to
      assess whether in coeliac children breath hydrogen excretion reflects the
      histological changes in the jejunal mucosa. Hydrogen breath test was performed on
      40 children (15 males 25 females) divided into three groups. Group I (controls):
      9 children with symptoms suggestive of coeliac disease who, after the appropriate
      workup, were found to suffer from other gastrointestinal disorders and had
      abnormal jejunal mucosa. Group II: 14 children who had been diagnosed as coeliacs
      according to the ESPGAN criteria, were kept on a gluten free diet for a minimum
      of 6 months and had a normal jejunal mucosa. Group III: 17 coeliac children who
      ate small quantities of gluten or were on a normal diet. At histology, 10 of them
      showed a total and 7 a partial atrophy of the jejunal mucosa. Breath hydrogen
      levels were measured both at baseline and after ingestion of a 2% sorbitol
      solution in water, at 30 minute intervals for four hours. The peak hydrogen level
      and the total surface area under the hydrogen excretion curve were also assessed.
      Coeliac children on a gluten containing diet excrete significantly more H2 than
      controls or coeliacs on a gluten free diet. Patients with more severe
      histological lesions had higher peak H2 levels and greater total excretion areas.
      In coeliac children, sorbitol breath H2 test represents a simple noninvasive
      technique to detect impaired jejunal function and it should have an important
      role as a screening test and in assessing dietary compliance.

PMID- 7731421
TI  - [Cytokines, immunostimulation and lactic enzymes].
AB  - On the basis of numerous experimental studies the authors advance the hypothesis
      of the use of lactoferments for immunomodulating purposes. This entails using a
      traditional and innocuous method for infantile prophylaxis and therapy, (adapted
      for immunodepressive and even iatrogenic syndromes) which might be assigned a new
      role through modern, large-scale experimental research.

PMID- 7731422
TI  - [Low cholesterol and pathological manifestations: Smith-Lemli-Opitz syndrome].

PMID- 7731423
TI  - Nutrition support in pancreatitis: fertile ground for prospective clinical
      investigation.

PMID- 7731424
TI  - Nutrition support in pancreatitis.
AB  - Nutrition support in patients with pancreatitis has created a challenge for
      clinicians. Because the pancreas is normally stimulated by the ingestion of food,
      particularly fat, patients are often denied oral nutrition. This reduction in the
      ingestion of food, together with the increased metabolic demands of this disease,
      often results in a negative energy balance and occasionally undernutrition or
      malnutrition. This review summarizes the etiologies and methods for staging
      pancreatitis, the physiology of pancreatic exocrine secretion and the response of
      the pancreas to different methods of nutrition support. The results of clinical
      trials, which examine both parenteral and enteral nutrition in animals and humans
      with this disease, are reviewed. Recommendations for nutrition management of
      patients with acute and chronic pancreatitis and areas for future research are
      discussed.

PMID- 7731425
TI  - Development of pediatric and neonatal parenteral nutrition order forms.
AB  - The diversity of nutritional needs within the pediatric population makes ordering
      parenteral nutrition (PN) for infants and children a difficult task for
      inexperienced clinicians. A well designed PN order form can simplify this task.
      Standard PN solutions, tables with age-specific nutrient requirements, and
      guidelines for advancing substrate may improve PN prescriptions and serve as an
      educational tool. The development of an optimal PN order form for an institution
      requires consideration of many factors, including the patient population,
      requirements of the institution, and the needs of the staff and students. One
      nutrition support team's experience in developing pediatric PN order forms is
      described.

PMID- 7731426
TI  - Femoral catheters increase risk of infection in total parenteral nutrition
      patients.
AB  - Central venous access for the administration of total parenteral nutrition is
      usually achieved via the subclavian or internal jugular veins. Although a high
      incidence of complications has been reported with the use of femoral catheters
      for central venous access, this route has been used when traditional central
      venous access is contraindicated. We retrospectively reviewed 171 patients who
      received total parenteral nutrition via a central venous triple-lumen catheter
      and compared the rates of infections in femoral vs nonfemoral access. A
      literature review was performed to identify associated complications of and
      appropriate indications for femoral catheter use. In the 171 patients studied,
      355 triple-lumen catheters were placed; these included 331 nonfemoral catheters
      and 24 femoral catheters. Femoral catheters were placed in nine patients. Femoral
      catheters had a greater incidence of positive tips (42% vs 6.9%, p < .001) and
      related bacteremia (16.7% vs 1.8%, p = .002) than did nonfemoral catheters. The
      organisms most commonly isolated from the blood and catheter tips of both
      catheter access sites were methicillin-resistant Staphylococcus epidermidis and
      Candida. The use of femoral catheters for central venous access for total
      parenteral nutrition administration results in an increased risk of infectious
      complications.

PMID- 7731427
TI  - Nutrition in the pediatric double lung transplant patient with cystic fibrosis.
AB  - Cystic fibrosis (CF) is the most common lethal genetic disease in the white
      population. The pulmonary infections and pancreatic insufficiency make CF a
      medically challenging disease. Although the importance of nutrition in the CF
      patient is known, approximately 50% of CF patients are in less than the 10th
      percentile for weight and height as reported by the 1991 CF Foundation Registry
      of 114 CF Centers in the United States. This paper addresses the nutritional
      status of 10 pediatric CF patients who underwent double lung transplant at
      Children's Hospital of Pittsburgh between August 1991 and May 1993. Patients who
      survived beyond 1 year gained a significant amount of weight sooner after
      transplant than those who survived less than 1 year. Gastrostomy tube feedings
      were more effective than oral intake for weight gain after transplant. CF
      patients with pancreatic insufficiency have more difficulty with adjustment of
      doses of immunosuppressive agents for reasons that are not clearly understood.

PMID- 7731428
TI  - Prolonged parenteral nutrition for cystic fibrosis patients.
AB  - To evaluate the clinical impact of prolonged parenteral nutritional (PN) therapy
      on patients with advanced cystic fibrosis, we conducted a retrospective chart
      review of 25 cystic fibrosis patients who underwent prolonged PN (median course
      295 days) at our institution between August 1988 and May 1992. The patients'
      survival status, change in percentage of ideal body weight, need for ongoing
      nutritional intervention, pulmonary function test changes, i.v. antibiotic use,
      and complication rates were assessed. Patients gained significant weight while
      receiving PN, but they lost weight when PN was discontinued. PN did not clearly
      improve pulmonary status. IV antibiotic therapy nearly doubled during PN. Central
      venous catheter sepsis rates rose from 1.29 to 3.45 per 1000 catheter days during
      PN therapy. In conclusion, prolonged PN promotes weight gain in cystic fibrosis
      patients with severe disease; however, the effect is transient and involves a
      significantly increased risk of sepsis.

PMID- 7731429
TI  - "Superior mesenteric artery syndrome" as a complication of enteral feeding.

PMID- 7731430
TI  - Promoting racial equality in the nursing curriculum.
AB  - Racial inequality in nursing is not a new concern and no doubt some nurses have
      and are still making stringent efforts singularly or through various
      organisations to address this issue. This paper outlines the current position
      within the context of racial equality, the objectives of nurse education and
      proposes how equal opportunities and anti-racist strategies could be instrumental
      in promoting equality in the nursing profession. Suggestions are also made as to
      what contents could be added to existing ones to produce nurse practitioners who
      are able to respond appropriately and sensitively to the health needs of a
      diverse client group. Methods of evaluating the effectiveness of equal
      opportunities and anti-racist strategies within the curriculum are also
      discussed.

PMID- 7731431
TI  - HIV/AIDS--an issue in nurse education.
AB  - The White Paper, The Health of the Nation (Department of Health 1991), identifies
      education in HIV/AIDS as an area of priority concern. Statistics have shown that
      education aimed specifically at gay men has been reduced and that, at the same
      time, the incidence of infection within this group has risen. There would appear
      to be a relationship between education targeted at a group and the behaviour of
      that group. For nurses there are similar implications. A study published in 1992
      found that there was widespread ignorance among nurses and that education and
      training targeted at the specific needs of nurses was the answer. There have been
      a number of other research studies which have focused on other aspects of
      HIV/AIDS education. The issues involved include: highlighting infection control,
      the education of Health Care Assistants, prejudice and attitude, the credibility
      of teachers. This study shows how a course on HIV/AIDS can be tailored to meet
      the identifiable learning needs of nurses as an ongoing process of monitoring and
      evaluation. The process endeavours to address the issues in a way that has
      maximum effect on the learning process and takes account of a range of studies in
      order to meet the requirements of the Health of the Nation White Paper.

PMID- 7731432
TI  - The value of critical incident analysis as an educational tool and its
      relationship to experiential learning.
AB  - Experiential learning and teaching strategies designed to facilitate this, have
      become popular in nursing and midwifery education in recent years. It is
      advocated that such learning enables the development of knowledge, skills and
      attitudes grounded in practice through the use of reflection on action. One
      strategy that may be utilised by nursing/midwifery educators to develop
      reflective ability in both themselves and students is critical incident analysis.
      It is suggested that critical incident analysis has value and is appropriate for
      developing interpersonal skills and self-awareness. It is proposed that critical
      incident analysis is a valuable educational tool which enables nursing/midwifery
      students to draw on past experiences and make sense of them, not only
      facilitating learning from clinical practice but also going some way towards
      bridging the gap between theory and practice.

PMID- 7731433
TI  - Writing for publication: a guide for those who must.
AB  - All nurse educators must write and most must publish. This paper outlines the
      principles that need to be observed if the nurse educator is to get his or her
      work into print. The paper offers a summary of the work that needs to be done
      before manuscript preparation, commentary on preparing the manuscript and a
      discussion of what must be done after the manuscript has been submitted. The
      paper concludes with the argument that writing for publication involves the
      learning of certain basic skill and the observation of certain conventions.

PMID- 7731434
TI  - Using medical dictionaries to teach the critical evaluation of information
      sources.
AB  - Bibliographic instruction (BI) is the formal teaching of information skills by
      library professionals. It is argued that biomedical BI must involve the teaching,
      not only of information retrieval, but also of evaluative skills. A course
      integrated BI session on the critical evaluation of health information sources is
      described. This session uses medical and nursing dictionaries as a subject for
      investigation. Students in small groups evaluate various dictionaries according
      to selected criteria. Then they rank the dictionaries and defend the ranking
      before the rest of the class. It appears to be an effective learning experience
      from which participants emerge with sharper evaluative skills.

PMID- 7731435
TI  - Nurse learners--do nurse tutors know them?
AB  - Research was undertaken to establish the social profile of Project 2000 (Diploma)
      learners, and to determine when, and with whose influence, learners make
      decisions to enter nursing. The image of nursing held by the group was sought and
      nurse tutors perceptions of the group were obtained, using a questionnaire
      method. Results analysed using statistical measures and content analysis showed
      that the majority of learners came from middle socio-economic backgrounds,
      generally decided to enter nursing whilst at school, and were influenced by
      nursing role models and the media. The learners perceptions and expectations of
      nursing were influenced by their experiences and showed some differences when
      compared with tutor responses. The findings from this small study imply the need
      for the dissemination of accurate and appropriate recruitment information to
      school personnel and career advisors. Effective marketing which addresses
      influences of the media and nursing role models should be employed, and finally
      nurse tutors need to be conversant with course content and learner expectations
      to facilitate effective recruitment policies and curriculum development.

PMID- 7731436
TI  - Clinical teaching in midwifery--an exploration of meanings.
AB  - This small study was carried out as part of the BEd (Hons) Course in Education,
      and was conducted in the author's practice placement, a college of health care
      studies attached to a large maternity unit. The aims of the study were to
      determine what is meant and understood by the term clinical teaching, to explore
      student midwives' experiences of clinical teaching, and to ascertain whether the
      transition from student to midwife influences approaches and attitudes to
      clinical teaching. A qualitative approach was adopted, using a phenomenological
      viewpoint; data sources consisted of transcripts from semi-structured interviews
      with the eight participants, field notes and the author's reflective diary. The
      main findings of the research suggest that clinical teaching is perceived as a
      didactic, teacher led activity which occurs in the clinical area but away from
      women and babies. Other significant learning in the clinical area arises almost
      by accident as students go about their work. This learning is viewed negatively,
      and not always capitalised upon. Becoming a qualified midwife, although exciting,
      is stressful; informants felt unsupported in their role, and considered
      themselves ill-prepared for the task of mentorship. Midwife teachers are valued
      in the clinical area, but they were considered to be out of touch and in a
      hierarchy of work, theirs was considered least important. The study proposes
      strategies to enhance clinical learning and describes two models which legitimise
      the role of the teacher in the clinical area.

PMID- 7731437
TI  - Project 2000: a modular approach to course planning.
AB  - Project 2000 has given nurse educators an opportunity to consider and plan
      educational programmes that will endure until the year 2000 and beyond. The
      United Kingdom Central Council for Nursing, Midwifery and Health Visiting (1986)
      highlighted the need for preparing practitioners for uncertainty by developing
      structures that adapt to rapid change. This includes planning smaller units of
      study, that are accessible and allow for credit transfers. This article describes
      the development of a semester based, modular programme of study, for Project
      2000. The idea of modularity, both from the higher education and nurse education
      perspective is examined. An outline of the course is offered and for the benefit
      of colleagues who may be considering embarking on a similar remit, areas of
      difficulty encountered on implementation are highlighted with some resolutions.

PMID- 7731438
TI  - The need for nursing and midwifery programmes of education to address the health
      care needs of minority ethnic groups.
AB  - The article reviews some of the more influential literature of the past decade on
      the health needs of ethnic groups, in an effort to identify what is being done by
      nursing and midwifery education to address the health care needs of these groups
      and to prepare practitioners who are able to respond to these needs. The article
      suggests that despite the relative lack of progress in this field of health care
      and education, there still exists much confusion, disagreement and lack of
      clarity around many issues, such as the identification of relevant content, the
      integration of this content into the curriculum and more importantly the delivery
      of this content. The literature seems to point to a lack of cultural knowledge,
      particularly for certain ethnic groups, which needs to be rectified. But even
      when knowledge is available, the evidence clearly indicates that both educators
      and practitioners are failing to translate this into effective and culturally
      sensitive care. The article suggests that nursing and midwifery education could
      and should play an important role in the development and dissemination of
      culturally sensitive care.

PMID- 7731439
TI  - Solving the problem of writing.
AB  - This paper explores the difficulties which some students appear to encounter with
      written work and recommends the teaching of a problem-solving approach.
      Exploration of the skills necessary for writing, e.g. language skills and memory
      functions, highlights the structured format of cognitive processes. Most study
      skill packages emphasise the need for planning and organising work. It may be
      that students require more detailed help and guidance in such skills. This paper
      promotes the teaching to students of a problem-solving approach to written work.
      We all solve problems every day, many we are completely unaware of. This approach
      seeks to harness these transferable skills and utilise them in a new area. It can
      be applied at a macro and at a micro level, i.e. the entire essay/project/report
      may be planned utilising this approach and then each section or paragraph further
      planned in the same manner. The use of a mnemonic further aids the student in
      developing and applying the problem solving approach to written work.

PMID- 7731440
TI  - The introduction of liberal studies into a Project 2000 nurse education course.
AB  - This paper discusses an attempt to introduce liberal studies into a Project 2000
      nurse education course. The paper reviews the origins of liberal studies and
      other attempts to nurture the 'whole person' in further and higher education, and
      describes a 'contract learning' approach to liberal studies adopted at one
      college of nursing. The results of an evaluative questionnaire completed by
      students about the liberal studies component of the course are outlined, and the
      implications discussed.

PMID- 7731441
TI  - A student reflects.

PMID- 7731442
TI  - The power of social judgement: struggle and negotiation in the nursing process.
AB  - In this paper we discuss an alternative view of the nursing process as it is
      experienced by both patients and nurses. The current conception of the nursing
      process is that it is a benevolent activity which aims to render care more
      individualized or person-centred. Its rhetoric usually includes notions of
      mutuality in goal setting, openness and collaboration between patients and
      nurses. We will suggest that such a view is idealized and has little basis in
      empirical reality as it is experienced by both nurses and patients. Rather, nurse
      patient relations are beset by conflict and struggle, frequently resulting in the
      acquiescence of patients to the nursing and the medical goals of care. On the
      basis of an ethnography of a hospital medical ward, we will describe a process of
      social judgement and set it into a discussion of the social context where an
      unequal balance of power is integral to provider-recipient relations. Our account
      will focus upon four categories through which judgemental labelling may be
      analysed. These are assessing, negotiation, struggling and acquiescing. Of
      special interest to us are strategies which nurses used to maintain excellent
      care in the context of negative social judgements, and the place social judgement
      may play in moral decision-making. We emphasize the strengths which rich
      qualitative data have in relation to previous survey approaches of this
      phenomenon, whilst recognising the limitations of so focused a study.

PMID- 7731443
TI  - Towards a new model of nursing education.
AB  - We are witnessing the most significant changes in the nature of the relationship
      between nursing education and higher education. However, there has yet to be a
      more philosophical explanation of what it would mean for our aims and practices
      as nurse educators if we were to take seriously the notion of nursing education
      within the context of higher education. This paper analyses the role of the
      university and raises the questions: What should higher education mean today?
      What should higher education mean for nursing? In response to the former question
      it is suggested there cannot be a total distinction between the concept 'higher
      education' and the socio-political context. Higher education has to be realized
      in particular historical societies and there is likely to be much controversy
      over how this should be done. In response to the latter question it is suggested
      that to warrant the title nursing 'higher education' the process should promise a
      freeing of the mind but also beyond, to bring about a new level of self
      empowerment in the individual student. In essence, it should contain an
      emancipatory element. It is the articulation of normative aspirations such as
      these, that is so strikingly absent from so much of the debate relating to
      nursing education merging with higher education. Nursing education must not
      however fall victim to 'academic drift' which has often been regarded as a
      distinctive and persistent feature of higher education. It might be proposed that
      student nurses who move from an educational to a practice setting are subjected
      to 'a competing paradigm of occupational vocationalism'.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7731444
TI  - Issues in the assessment of expert nurses: purposes, standards and methods.
AB  - It is generally agreed that experts seek and use different information, and that
      the solutions they propose and implement are also different in kind and quality
      from those of non-experts. This makes assessment of experts a challenging
      problem. The difficulty of establishing standards and criteria by which the
      expert can be assessed should not necessarily prevent such assessment from being
      undertaken. However, the purpose of assessing experts should be clearly
      articulated before engaging in such practices, since different purposes may
      legislate different assessment methods. This paper canvasses concerns relating to
      the assessment of expert nurses, including: the definition of expertise;
      establishing standards of expert nursing performance; the training of appropriate
      assessors; and the choice of assessment method. Care needs to be exercised at all
      times to avoid obscuring the issues by concentration on assessing isolated expert
      behaviours to the exclusion of consideration of the underlying political purposes
      and the economic consequences of assessing expertise.

PMID- 7731445
TI  - Otolaryngology quiz #2. Bronchial foreign body.

PMID- 7731446
TI  - The medical marketplace needs more, not less, regulation: managed care strives to
      escape accountability.

PMID- 7731447
TI  - Decisions in severe extremity trauma.
AB  - Advances in the management of severe extremity trauma have allowed treatment of
      injuries previously resulting in amputation or death. The variety of new
      techniques and technologies available to the orthopedic traumatologist and the
      trauma team can lead to functional salvage of limbs if crucial management
      decisions are made correctly in the course of treatment. Accurate knowledge of
      the potentials and pitfalls of extremity trauma treatment can help to identify
      salvageable limbs, as well as those doomed to failure so that costly and painful
      courses of futile treatment can be avoided.

PMID- 7731448
TI  - Voice rehabilitation after laryngectomy.
AB  - Unfortunately, laryngeal cancer commonly presents at a stage necessitating total
      laryngectomy. Voice rehabilitation in the past has primarily been with the
      electrolarynx or esophageal speech. Tracheoesophageal puncture (TEP) is a
      technique that has replaced the other two methods as the rehabilitative procedure
      of choice in most total laryngectomy patients. This report details this
      technique, as well as a brief discussion of the etiology and treatment of
      laryngeal cancer.

PMID- 7731449
TI  - Patient-focused care: what it is--what it is not.

PMID- 7731450
TI  - Clinically speaking: issues in designing the NICU.

PMID- 7731451
TI  - Imported dengue--United States, 1993-1994.
AB  - Dengue is a mosquito-transmitted acute disease caused by any of four virus
      serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) and characterized by the sudden onset
      of fever, headache, myalgia, rash, nausea, and vomiting. The disease is endemic
      in most tropical areas of the world and has occurred in U.S. residents returning
      from travel to such areas. This report summarizes information about cases of
      imported dengue among U.S. residents during 1993 and 1994.

PMID- 7731452
TI  - Carbon monoxide poisoning from use of gasoline-fueled power washers in an
      underground parking garage--District of Columbia, 1994.
AB  - On June 17, 1994, five workers in the District of Columbia were treated in an
      emergency department for carbon monoxide (CO) poisoning following exposure to the
      exhaust from two gasoline-fueled power washers (i.e., pressure washers), which
      they had used in an empty underground parking garage. These cases were identified
      by The George Washington University (GWU) Division of Occupational and
      Environmental Medicine (DOEM) through ongoing surveillance for work-related
      injuries among construction workers treated in the GWU emergency department (1).
      This report summarizes the results of an investigation by DOEM of this incident.

PMID- 7731453
TI  - Eye injuries to agricultural workers--Minnesota, 1992-1993.
AB  - During 1993, U.S. farm workers incurred an estimated 13,500 eye injuries that
      resulted in lost work time (1); many of these injuries could have been prevented.
      To determine the incidence of eye injuries and use of eye protection among farm
      workers, the Minnesota Occupational Health Nurses in Agricultural Communities
      (OHNAC)* examined data from the Minnesota Farming Health Survey (MFHS) conducted
      during January-April 1992 and December 1992-April 1993. This report summarizes
      the results of this analysis.

PMID- 7731454
TI  - [Local spread of carcinoma of the esophagus by perineural invasion].
AB  - For clarification of the clinico-pathological features of carcinoma of the
      esophagus by perineural invasion (pni), 107 resected specimens were
      histologically examined. A correlation between pni and other findings, including
      clinical results, was sought. Pni was found in 31 patients (29.0%). It was found
      in no cases without adventitial cancerous invasion, at 26.3% in a1, 36.5% in a2
      and 66.7% in a3. Pni would thus appear to be closely correlated with the depth of
      invasion. It also showed correlation with lymph-canal invasion but not with
      venous invasion or lymph node metastasis. Pni positivity was the same regardless
      of patient's age and sex, as well as tumor size, location and histological
      differentiation. In patients who had undergone preoperative radiotherapy, lymph
      canal and venous invasion were noted to have markedly decreased but not pni.
      Curative resection was carried out in 57.9% of the pni negative patients and in
      32.3% of the pni positive. Local recurrence was observed in 30.0% of pni positive
      and only 4.5% of negative cases. The cumulative survival rate was not
      significantly less in positive compared to negative patients.

PMID- 7731455
TI  - [Intraportal infusion of 5-FU and lipiodol-aclarubicin after hepatic resection
      for colorectal liver metastasis].
AB  - Fifty-five patients with hepatic metastasis from colorectal cancer underwent
      curative hepatic resection. Postoperative intraportal infusion of 5-fluorouracil
      (500mg per day) for 14 days from 21 postoperative days (POD) and lipiodol
      aclarubicin (40mg) at 35 POD was carried out in twenty-eight patients for
      reducing the recurrence in the remnant liver and improving the prognosis. Twenty
      seven patients had hepatectomy alone as controls. Intraportal infusion
      chemotherapy did not induce any hepatotoxicity and hematologic severe
      abnormalities. The cumulative survival rates for the infusion group and the
      control group, respectively, were 89.3% and 63.0% at 1 year; 55.2% and 43.3% at 2
      year; 27.0% and 27.5% at 3 year. The survival rate for the infusion group was
      significantly higher than that for the control group at 1 year (p < 0.05). No
      difference of the recurrent rate in the remnant liver was found between the two
      groups. It is suggested that intraportal infusion chemotherapy after curative
      hepatic resection for colorectal liver metastasis might improve survival rate at
      the early postoperative period. Intraportal infusion chemotherapy could be an
      effective adjuvant therapy especially in the patients with bilateral and multiple
      hepatic metastasis.

PMID- 7731456
TI  - [Quantitative changes of hepatic microcirculation and mitochondrial function
      after splenectomy in liver cirrhosis rats].
AB  - To evaluate the potential risk of splenectomy for patients with cirrhotic liver.
      I measured quantitative time-course changes of portal pressure (PP), and hepatic
      tissue blood flow (TBF) by hydrogen clearance method and adenine nucleotides by
      HPLC in a rat model. Intraperitoneal thioacetamide injection (200mg/kg x 30)
      produced histologically proven cirrhotic liver (TAAs) as well as increasing the
      spleen weight and PP compared to controls. PP and TBF simultaneously decreased on
      the 1st postoperative day (POD) after splenectomy in TAAs, whereas controls
      showed no changes in these parameter after splenectomy. Although PP of TAAs
      remained decreased until the 7th POD after splenectomy, their TBF gradually
      increased between the 2nd and 7th PODs returning to the baseline value. Recovery
      of ATP or energy charge after their decrease on the 1st POD was delayed in TAAs.
      Splenectomy in TAAs enhanced the deterioration of energical metabolism.
      Splenectomy in cirrhotic rats resulted in an additional postoperative risk.

PMID- 7731457
TI  - [Efficacy of local immunosuppression with intraportal administration of
      cyclosporine in liver transplantation].
AB  - The purpose of this study was to evaluate the efficacy of local immunosuppression
      with intraportal administration of cyclosporine (CsA) in liver transplantation.
      Mongrel dogs weighing 12-18kg were used. Orthotopic liver transplantation was
      performed, and animals were divided to the following groups. Group I (n = 7): no
      treatment, group II (n = 7): CsA 5mg/kg/day intermittent iv, group III (n = 5):
      CsA 3mg/kg/day continuous iv and group IV (n = 8): CsA 3mg/kg/day continuous
      portal infusion. Immunosuppressive treatments were carried out for two weeks
      postransplant. Median survival time (MST) of group IV was significantly prolonged
      (MST = 18 days, range 10-85 days; p < 0.025) compared with group I (7 days, range
      6-13), group II (10 days, range 7-16) and group III (7 days, range 6-10). Data of
      blood chemical analyses showed that hepatic dysfunction was significantly
      diminished in group IV compared with other groups (p < 0.05). Blood concentration
      of CsA on the 5th day (mean +/- SEM) was significantly lower in group IV (238 +/-
      22ng/ml) than in group III (438 +/- 113ng/ml). Histologic findings showed that
      rejection reaction was effectively suppressed in group IV, although SG2M% (mean
      +/- SEM) of peripheral mononuclear cells of group IV (10.6 +/- 3.3%) was equal to
      that of group III (11.3 +/- 1.7%). In conclusion, local immunosuppression could
      achieve prominent effect in preventing hepatic graft rejection with limited
      systemic immunosuppression.

PMID- 7731458
TI  - [A clinico-pathological study on prognosis in node-negative breast cancer].
AB  - In recent study, recurrence was seen in about 10% patients with node negative
      breast cancer during 10 years after operation. I evaluated prognostic factors
      including tumor diameter on the cut surface, histological infiltration diameter,
      histological malignancy, and expression of c-erbB-2 oncoprotein in 779 patients
      with node-negative breast cancer. The patient were operated from 1960 to 1972 at
      the Cancer Institute Hospital, Tokyo. The overall survival rate in this series
      was 88.6% at ten years. The survival rate at ten years for patients with tumor
      more than 21mm in size was 82.6%, and for those with tumor more than 11mm in
      filtrated size was 83.1%. On the other hand, marked fatty tissue infiltration,
      marked lymphatic vessel invasion, extensive histological invasion and numerous
      mitosis were associated with poor prognosis. The expression of c-erbB-2
      oncoprotein correlated with recurrence within 5 years.

PMID- 7731459
TI  - [Therapeutic efficacy of hepatectomy in the treatment of hepatic metastases from
      breast cancer].
AB  - This study was performed to evaluate whether or not surgical excision of hepatic
      metastases from breast cancer has any effect on the prognosis. Between September
      1985 and April 1993, eight patients with hepatic metastases (solitary in four
      cases, multiple in four cases) underwent hepatectomy. Two patients among them had
      other remote recurrence besides that arising in the liver. Right hepatectomy in
      two cases, left hepatectomy in one, extended left hepatectomy in one and partial
      hepatectomy in four were done. No postoperative complications developed. Four
      patients incurred liver recurrence within an average period of 11.5 months after
      hepatectomy, with three of average period of 11.5 months after hepatectomy, with
      three of them dying from the disease within 16 to 36 months after hepatectomy.
      The other four were free of liver recurrence and remained alive for 3 to 65
      months post-operatively. The 50% survival time was 36 months after hepatectomy
      and 40 months after the discovery of hepatic metastases. Although hepatectomy
      could only be applied to a restricted number of patients and these results are
      obviously insufficient, we believe that surgical procedure for liver metastases
      from breast cancer, if possible, is undoubtedly beneficial in prolonging the
      survival in such patients.

PMID- 7731460
TI  - [Comparison of the long-term results of intra or extracardiac implanted
      bioprosthetic valves].
AB  - The long-term results following intra or extracardiac implanted bioprosthetic
      valves were compared. Forty-one patients, whose average age at the operation was
      43.3 +/- 10.7 (mean +/- SD) year-old, were implanted 33 Hancock and 11 Carpentier
      Edwards porcine valves, 35 in mitral, 6 in aortic and 3 in tricuspid position.
      Twenty-five children, whose average age was 6.0 +/- 3.5 year-old (p < 0.01) at
      the operation, underwent right ventricular-pulmonary artery conduit repair with
      16 Hancock, 7 Carpentier-Edwards porcine valves and 2 Ionescu-Shiley pericardial
      valves. There were only one late death and one operative death in the patients
      implanted intracardiac bioprosthetic valves. Seven intracardiac and 12
      extracardiac implanted bioprosthetic valves were removed at the reoperation for
      prosthetic valve dysfunction. The probabilities free from reoperation after 7 and
      9 years of follow-up was 91% and 82%, respectively, with intracardiac implanted
      valves, on the other hand 51% (p < 0.05) and 8.6% (p < 0.05), respectively, with
      extracardiac implanted valves. Valve dysfunction in extracardiac implantation was
      mainly related to the stenosis due to fusion of comissure and/or calcification.
      Regurgitation due to tear and/or perforation was mainly associated with
      intracardiac implanted bioprosthetic valves.

PMID- 7731461
TI  - [Enlargement of the internal thoracic artery with intact vascular wall structure
      by construction of an arterio-venous shunt].
AB  - The purpose of this investigation was to examine whether construction of an
      arterio-venous shunt could enlarge the internal thoracic artery (ITA) and
      preserve normal structure of the vascular wall. Five mongrel dogs were used. Side
      to-side anastomosis was made between the left ITA and left internal thoracic
      vein. These dogs were followed for about 6 weeks and diameters of bilateral ITAs
      were determined by angiography. The diameter of the left ITA was 2.67 +/- 0.5mm,
      which was significantly larger than the right ITA (2.24 +/- 0.4mm, as control, p
      < 0.01). The right to left ITA ratio was 119.4 +/- 6.9%. There was no significant
      difference in the morphologic features of endothelial cells between left and
      right ITAs. Several specimens of the left ITA showed morphologic changes of
      protruding nucleus, widening of intercellular junctions and creater formation.
      There was no significant difference between the ITAs with respect to thickness of
      media and the number of elastic fibers in the media. The smooth muscle cells just
      under the internal elastic lamina didn't appear to be synthetic phenotype. In
      conclusion, arterio-venous shunting enlarged the diameter of ITA, and caused
      minimum morphologic change in the intima and media.

PMID- 7731462
TI  - [A case report of a metaplastic carcinoma of the breast diagnosed by the
      preoperative needle biopsy].
AB  - A case of the metaplastic carcinoma, a rare type of the breast cancer, was
      reported. A 49-year-old woman noticed the left breast lump. Ultrasonography
      revealed a well circumscribed hypoechoic mass measuring 3 cm in diameter. The
      preoperative needle biopsy showed the invasive carcinoma with chondrometaplasia.
      The modified radical mastectomy along with the lymph node dissection was
      performed. There have been few reports of the metaplastic breast carcinoma
      diagnosed preoperatively.

PMID- 7731463
TI  - [A case report: abdominal aorta-femoral artery bypass grafting in patient with
      essential thrombocythemia].
AB  - A 58-year-old man was admitted to our hospital suffering from intermittent
      claudication and angiogram revealed complete obstruction of the left common iliac
      artery. The essential thrombocythemia was diagnosed from platelet count over
      1,000,000/mm3 as well as bone marrow finding. After the platelet count was
      reduced into normal range by administration of ranimustine (MCNC), abdominal
      aorta-femoral artery bypass grafting using 8mm-diameter Gelseal graft was
      successfully performed without any complications such as thrombus formation or
      bleeding. Coldness and cyanotic discoloration of the lower extremities were
      diminished with the decrease in platelet count. He was discharged in satisfactory
      condition and has been on postoperative control with warfarin, ticlopidine
      chloride and aspirin therapy.

PMID- 7731464
TI  - [Aortic dissection, sometimes a difficult diagnosis].

PMID- 7731465
TI  - [Helicobacter pylori infection as causal factor in the development of carcinoma
      and lymphoma of the stomach; report WHO consensus conference].

PMID- 7731466
TI  - [Controlled distribution of new medical technology: transfemoral placement of an
      endoprosthesis in the treatment of an abdominal aortic aneurysm].

PMID- 7731467
TI  - [Treatment of an infrarenal aortic aneurysm using a transfemorally-placed
      endoprosthesis: initial results in 9 patients in The Netherlands].
AB  - OBJECTIVE: To describe the first experiences with transfemoral aortic
      endoprostheses for treatment of aortic aneurysms in the Netherlands. SETTING:
      University Hospital Utrecht, The Netherlands. METHOD: Patient selection was based
      on information presented on CT and angiography films. Only patients with an
      asymptomatic aneurysm and non-dilated aortic segments both distal from the renal
      arteries and proximal to the aortic bifurcation were selected. Of 71 patients
      screened only nine candidates were selected. RESULTS: The placement of the
      endoprosthesis was initially successful in all patients. The duration of the
      operation varied from 60 to 160 min. An intimal lesion of the common femoral
      artery occurred in one patient. In three cases leakage of contrast material
      outside the prosthesis but inside the aneurysm was seen on the postoperative CT
      angiogram. In one patient the endoprosthesis had to be replaced by a conventional
      aortic tube graft on the second postoperative day. After the procedure the
      patients stayed in hospital for another 3 to 20 days (median: 5). CONCLUSION:
      Endovascular treatment of infrarenal abdominal aneurysm is a promising technique.
      The main advantages to the patient are that laparotomy is not necessary and that
      the hospital stay is reduced.

PMID- 7731468
TI  - [Results of the introduction of laparoscopic cholecystectomy on morbidity and
      mortality of gallbladder surgery in a large regional hospital].
AB  - OBJECTIVE: To analyse the impact of the introduction of laparoscopic
      cholecystectomy on overall morbidity and mortality of gall bladder surgery.
      DESIGN: Retrospective study. SETTING: Medisch Centrum Alkmaar, Alkmaar. METHODS:
      All cholecystectomies performed in our final 'prelaparoscopic' year 1990 were
      compared with all cholecystectomies performed in 1992, the year in which
      laparoscopic cholecystectomy has become a standard procedure, thus eliminating
      selection bias. The analysis included morbidity and mortality related to all
      procedures. RESULTS: In 1990, 173 open cholecystectomies were performed, in 1992
      40, and 146 laparoscopic ones; the conversion rate was 4%. The number of patients
      undergoing investigation for common bile duct stones did not change, but there
      was a shift from intraoperative cholangiography to preoperative ERCP. In 1992
      more endoscopic sphincterotomies were performed (13.5%, versus 5.4% in 1990; p =
      0.02). One patient died from complications due to diagnostic ERCP. There was no
      difference in mortality rate of all procedures taken together, between the two
      years (3/186 in 1992 (1.6%); 2/173 in 1990 (1.2%)). The morbidity rate of all
      procedures in 1992 was slightly less than in 1990 (chi 2 = 1.91; p = 0.2). There
      were no common bile duct injuries caused by laparoscopy. In 1992, the mean
      operation time was longer than in 1990 (82 versus 46 min; p < 0.001) and the
      median postoperative hospital stay was significantly shorter than in 1990 (2
      versus 6 days; p < 0.001). CONCLUSION: Introduction of laparoscopic
      cholecystectomy was responsible for shorter hospital stays and longer operation
      times. When common bile duct stones were predicted, endoscopic sphincterotomy was
      performed more frequently. These changes did not negatively influence morbidity
      and mortality rates for gall bladder surgery in general.

PMID- 7731469
TI  - [Chronic arthralgia: not a precursor of rheumatoid arthritis, but part of
      fibromyalgia syndrome].
AB  - OBJECTIVE: To determine the characteristics and the course of chronic arthralgia
      (CA) and the differences from newly diagnosed rheumatoid arthritis (RA). DESIGN:
      Retrospective, with a follow up after 2.5 years. SETTING: Outpatient clinic for
      rheumatology of the St. Antonius Hospital, Nieuwegein, The Netherlands. METHOD:
      The diagnosis of CA was made in the period of June 1986-December 1988 in 74
      patients. The CA patients were sent a questionnaire after a mean of 2.5 years and
      invited for another rheumatological examination; 62 patients responded (84%).
      Data were compared with all 52 RA patients newly diagnosed in the same period by
      the same specialist. RESULTS: At the first visit CA had been present for 1 year,
      RA patients had had complaints for 0.6 years (p = 0.02). The RA patients had
      elevated BSE rates more often (31 vs. 8 mm in CA) (p < 0.0001) and more serious
      morning stiffness (75 vs. 0 minutes in CA) (p < 0.0001). The diagnosis of RA was
      made at the first visit in 86% and in 96% within half a year later. None of the
      CA patients developed an inflammatory joint disease within 2.5 years. In 1 out of
      3 CA patients the diagnosis of fibromyalgia was made and more than 50% had
      complaints. CONCLUSIONS: CA for more than 3 years does not predict inflammatory
      rheumatic disease. In contrast, RA develops in a short period and the diagnosis
      is made in 96% within 1 year. CA can be considered a feature of the fibromyalgia
      syndrome.

PMID- 7731470
TI  - [Cure of a low-grade gastric lymphoma following treatment of Helicobacter pylori
      infection].

PMID- 7731471
TI  - [Screening: current possibilities, new controversies?].

PMID- 7731472
TI  - [Disease clusters, 'your own backyard' and demographic synchronization].

PMID- 7731473
TI  - [Treatment of hypercholesterolemia in the elderly].

PMID- 7731474
TI  - [Chronic lymphocytic and prolymphocytic leukemia].

PMID- 7731475
TI  - [Complications of an intravenous administration system (Port-A-Cath) in children
      with an oncologic disease].
AB  - OBJECTIVE: To describe complications of the use of an intravenous administration
      system (Port-A-Cath; PAC) in children. DESIGN: Retrospective record analysis.
      SETTING: Emma Children's Hospital, the Children Academic Medical Centre,
      Amsterdam. METHOD: From January 1989 to January 1992, 66 children aged 1 to 20
      years were treated via a PAC system for malignant disease. 70 PACs were implanted
      with a cumulative period of use of 27,981 days. RESULTS: In one-third of the
      patients (36%) one or more complications arose. Most common were infection (16
      times) and obstruction (8). Tip dislocation, secondarily infected haematoma,
      leakage, thrombosis and infiltrate occurred occasionally. Almost 50% of the
      complications could be treated effectively. In the other cases the PAC system had
      to be removed. CONCLUSION: The advantage of a PAC for oncological patients is the
      improvement of the quality of life, as it provides a simple and painless access
      to the venous system. Complications occur regularly, however. Reduction of the
      number of complications should be the start of further perfection of the PAC
      system.

PMID- 7731476
TI  - [Consensus soft tissue tumors. Dutch Workgroup Soft-Tissue Tumors].
AB  - Soft-tissue sarcomas constitute a rare group of malignant tumours with
      histopathological features of connective, muscular, fatty or peripheral nervous
      tissue. The prognosis at manifestation depends on only two factors: the spread,
      both local and remote, and the biological behaviour of the tumour. The latter
      factor cannot be influenced but the former can: by inexpert manipulation.
      Consequently, tumours suspected of being soft-tissue sarcomas require
      multidisciplinary management from the beginning, with the team members familiar
      with each other's diagnostic and therapeutic skills. Imaging diagnostic methods
      should precede invasive methods for collection of material for pathological
      examination. The number of mitotic figures observed at microscopical examination
      of the tissue is an important prognostic feature. Surgical resection is the
      treatment of first choice. Radiotherapy is indicated in grade 3 tumours, after
      recurrence surgery, and when radical resection would involve too much mutilation.
      Chemotherapy is only given in the context of clinical trials. Surgical treatment
      of lung metastases may be indicated in selected patients. Regional isolated
      perfusion with tumour necrosis factor may be an alternative for limb amputation.

PMID- 7731477
TI  - [The dynamic trachea stent for treatment of benign and malignant tracheal
      obstruction].
AB  - Severe obstruction of the trachea is a life-threatening condition. In two
      patients with a benign cause of obstruction, women of 70 and 71 years old, and in
      one with a malignant cause, a man of 24 years old, insertion of a dynamic trachea
      stent led to instant relief of symptoms. The dynamic stent has the advantage over
      rigid or self-expanding stents that it does not migrate but may be easily
      removed, that it induces less granulation tissue, and that less mucus retention
      is seen, because it allows the normal cough mechanism to take place.

PMID- 7731478
TI  - [Travel experiences in Central and Eastern Europe; official amber in the Baltic
      States].

PMID- 7731479
TI  - [Frequency and determinants of episiotomy in second-line obstetrics in The
      Netherlands].

PMID- 7731480
TI  - [One antibody preparation is not the other: the role of passive immunotherapy in
      the treatment of HIV infections].

PMID- 7731481
TI  - Evaluation of growth hormone secretion in children with juvenile rheumatoid
      arthritis and short stature.
AB  - Children with juvenile rheumatoid arthritis (JRA) often exhibit delayed skeletal
      development. Previous evaluations of growth hormone (hGH) levels in these
      children have used single-value blood determinations. We sought to extend
      information on possible hGH deficiency in children with short stature and JRA by
      measuring 24-hour hGH pulsatile secretion. Five children with JRA were identified
      as having a height less than the 3rd percentile, and one child with a height at
      the 25th percentile. Three of these had abnormally low 24-hour serum hGH
      secretion. Two underwent a 24-month trial of human recombinant hGH; both
      exhibited only marginally accelerated growth. These results suggest that children
      with JRA and persistent short stature may have low hGH secretion without an
      adequate physiologic response to exogenous hGH administration.

PMID- 7731482
TI  - Distribution of insulin-like growth factor receptors in rat intestinal
      epithelium.
AB  - In summary, we present data from affinity cross-linking and Scatchard plot
      analysis that demonstrates the presence of both IGF-I receptors and IGF-II
      receptors on the brush border membranes of rat intestinal mucosa. The brush
      border location of the IGF receptors suggests that IGFs available in the
      intestinal lumen may initiate signal transduction events by binding to receptors
      displayed on the mucosal lining. Our findings provide further support for the
      notion that at least some of the mitogenic stimulus for rapid proliferation of
      intestinal epithelium arises from lumenal IGFs, which may be supplied by apical
      secretions from the mucosa, or in saliva, colostrum, milk, chyme, or bile.

PMID- 7731483
TI  - Use of a nurse in an orthopaedic foot and ankle practice.

PMID- 7731484
TI  - Netherlands Society of Gastroenterology and Netherlands Society of Hepatology
      meeting. Veldhoven, 27-28 October 1994. Abstracts.

PMID- 7731485
TI  - Non-invasive imaging of the arterial wall: new perspectives on atherosclerosis?

PMID- 7731486
TI  - Improved outcome for patients with a cardiac arrest by supervision of the
      emergency medical services system.
AB  - BACKGROUND: The outcome for patients with an out-of-hospital cardiac arrest can
      only be improved through optimal pre-hospital therapy by the emergency medical
      services (EMS) system. So far it is not clear if physician supervision of the EMS
      system is necessary for an optimal result. METHODS: In a retrospective and
      prospective case series we describe the changes in outcome for patients with an
      out-of-hospital cardiac arrest after the implementation of limited physician
      supervision of the EMS system. We also analysed the factors that were responsible
      for these changes. RESULTS: We studied 479 consecutive patients with an out-of
      hospital cardiac arrest. In the pre-intervention period, the survival rate for
      patients with an out-of-hospital cardiac arrest was 13%. This increased to 21.6%
      when physician supervision was implemented (p = 0.013). This increase in survival
      coincided with an improvement in pre-hospital advanced cardiac life support with
      an increase in the number of patients who arrived with a stable cardiac rhythm in
      the emergency department (p < 0.001). CONCLUSIONS: Limited physician supervision
      of an EMS system in a non-metropolitan area may improve the outcome for patients
      with an out-of-hospital cardiac arrest.

PMID- 7731487
TI  - Reversible nephrotic syndrome due to high renin state in renovascular
      hypertension.
AB  - Unilateral renal artery stenosis can lead to a non-functional kidney which
      secretes large amounts of renin. Four cases are presented in which the high renin
      state resulted in hypertension, proteinuria from the intact contralateral kidney,
      and secondary aldosteronism. The proteinuria was in the nephrotic range, which is
      unusual in renovascular hypertension, but gradually disappeared after correction
      of the high renin state by removal of the renin-secreting kidney or
      administration of an ACE inhibitor. Accordingly, when there is marked proteinuria
      in the presence of new-onset or rapidly progressive hypertension, hypokalaemic
      alkalosis, and a high peripheral PRA, renal artery stenosis should be considered
      since the proteinuria may be reversible after nephrectomy, repair of the
      ischaemic kidney or medical therapy.

PMID- 7731488
TI  - Clinical usefulness of abdominal CT-scanning in Henoch-Schonlein vasculitis.
AB  - The abdominal CT appearance is reported in a patient with Henoch-Schonlein
      vasculitis having symptoms of acute abdomen. Initial CT-scan showed segmented
      mural thickening of the small bowel loops, strongly suggesting the diagnosis of
      gastrointestinal involvement of vasculitis. Adequate treatment was started
      without the need for laparotomy. The CT appearance completely resolved after
      steroid therapy. Abdominal CT-scanning seems useful in the differential diagnosis
      of acute abdomen in patients with vasculitis.

PMID- 7731489
TI  - Heparin-induced thrombocytopenia and thrombosis: a potential fatal complication
      in a routine treatment.
AB  - Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin
      therapy. Life-threatening thromboembolism (HITT) may occur in a large number of
      patients with HIT. In this article diagnostic problems and the clinical course of
      4 typical patients are described. Diagnosis was based on the occurrence of
      thrombocytopenia during heparin therapy and was confirmed in vitro by an ELISA to
      heparin-platelet factor 4 antibodies, heparin-induced platelet activation assay
      (HIPAA) or the platelet aggregation assay (PAA). Thrombotic complications
      developed in 2 patients, one of whom suffered a fatal embolism after accidentally
      rechallenging with low-dose heparin which was used to maintain the patency of an
      intravascular catheter. After discontinuation of heparin the thrombocyte count
      rapidly increased to normal values during treatment with the heparinoid
      danaparoid (Orgaran) without complications.

PMID- 7731490
TI  - Septic shock caused by group G beta-haemolytic streptococci as presenting symptom
      of acute myeloid leukaemia.
AB  - A patient with rapidly fatal septic shock caused by group G beta-haemolytic
      streptococci as presenting symptom of acute myeloid leukaemia is presented.
      Although the association of septic shock due to Group G beta-haemolytic
      streptococci and different kinds of malignancy is known, presentation of acute
      myeloid leukaemia in this form is rare.

PMID- 7731491
TI  - Magnesium therapy in acute myocardial infarction.
AB  - The trials reviewed in this study investigated the effect of intravenous
      magnesium on arrhythmias and mortality in acute myocardial infarction. Nine
      trials were carried out in the pre-thrombolytic era. They varied in set-up,
      number of patients, dose of magnesium, follow-up and the type of arrhythmias
      analyzed. Magnesium reduced mortality in most studies, but the reduction was
      significant in only three of them. Two meta-analyses of the smaller studies
      revealed a 55% reduction in mortality. In the LIMIT-2, in which 2300 patients
      were enrolled, magnesium reduced mortality significantly by 24%. The effect of
      magnesium on arrhythmias was less clear. Preliminary results of ISIS-4, in which
      magnesium among others was administered together with thrombolytic agents, did
      not provide evidence of benefit in patients with suspected myocardial infarction.
      At present there are no arguments for the use of magnesium in acute myocardial
      infarction.

PMID- 7731492
TI  - Distribution of estrogen receptor-immunoreactive cells in monkey hypothalamus:
      relationship to neurones containing luteinizing hormone-releasing hormone and
      tyrosine hydroxylase.
AB  - The precise sites and mechanisms by which gonadal steroids influence the activity
      of neuroendocrine cells controlling pituitary hormone secretion are poorly
      understood. The present study has determined the distribution of estrogen
      receptor (ER)-immunoreactive cells in the monkey hypothalamus and examined
      whether ERs are expressed by luteinising hormone-releasing hormone (LHRH)-and/or
      dopamine-containing neurones. The distribution of ER-immunoreactive cells was
      determined in ovariectomised (n = 2) and estrogen plus progesterone-treated (n =
      2) cynomolgus macaques and in a single ovariectomised African green monkey. Large
      numbers of cells immunoreactive for the ER were detected in the preoptic area,
      bed nucleus of the stria terminalis, periventricular area and ventromedial and
      arcuate nuclei of all monkeys irrespective of the steroid status. Smaller numbers
      of ER-immunoreactive cells were found in the paraventricular, but not supraoptic
      nucleus. Double-labeling experiments in sections from all 5 monkeys revealed that
      none of the 432 LHRH neurons examined possessed detectable ER immunoreactivity.
      Neurones stained for tyrosine hydroxylase (TH) were identified in the A11, A12,
      and A14 cell groups and, although A11 and A12 neurones were intermingled amongst
      and found adjacent to ER-immunoreactive cells, none of the 1,652 TH
      immunoreactive cells examined contained ER immunoreactivity. These results show
      that ER-immunoreactive cells in the monkey hypothalamus are distributed in a
      manner similar to that observed in other mammalian species although not all brain
      regions reported to contain progesterone receptors (PRs) in these species of
      monkey were found to express ERs. The double-labelling experiments provide
      further evidence that LHRH neurones do not possess ERs and indicate that, as in
      other species, estrogen influences on primate LHRH neurones are indirect and/or
      non-genomic in nature. Unlike the rat and sheep, no evidence was found for ER
      immunoreactivity in hypothalamic dopaminergic neurones of the monkey. The
      discrepancy in ER and reported PR receptor localisation within specific
      hypothalamic nuclei as well as in dopaminergic neurones raises the possibility
      that not all PR-containing cells may express ERs in the primate hypothalamus.

PMID- 7731493
TI  - Stimulatory effects of 5HT1A receptor agonists on luteinizing hormone-releasing
      hormone release from cultured fetal rat hypothalamic cells: interactions with
      progesterone.
AB  - Previous works have suggested an interactive stimulatory effect of progesterone
      (P) and serotonin (5-HT) on luteinizing hormone release. The purpose of the
      present study was to determine whether 5-HT via 5-HT1A receptors interacts with P
      in the process of luteinizing hormone-releasing hormone (LHRH) release. Using
      fetal hypothalamic neurons in primary cell cultures the first goal of this study
      was to determine the effects of 5-HT1A receptor agonists on LHRH secretion. 8
      Hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) or ipsapirone (10(-5) M)
      significantly stimulated LHRH release. Pharmacological studies have allowed to
      rule out the possible involvement of alpha 2- or beta-adrenoreceptors, or 5-HT
      uptake sites, in the stimulatory effect of 8-OH-DPAT on LHRH release, thus
      demonstrating the specific involvement of 5-HT1A receptors in the stimulation of
      LHRH release. The second goal was to test the ability of P to stimulate LHRH
      release from fetal hypothalamic neurons. P (10(-6) M) applied for 30 or 120 min
      significantly stimulated LHRH secretion. The maintenance of the stimulation of
      LHRH release by P after a cycloheximide treatment or by an impermeable analog of
      P, P-3-BSA, has suggested a nongenomic effect of P on LHRH release. The effects
      of a pretreatment of cells by P on 8-OH-DPAT-induced LHRH release were tested.
      While 10(-7) M P alone did not stimulate LHRH release, this concentration of
      steroid potentiated the LHRH response to 10(-5) M 8-OH-DPAT. These findings led
      to the conclusion that P acting at the level of the plasma membrane potentiates
      the stimulatory effect of 5-HT1A receptor agonists on LHRH release.

PMID- 7731494
TI  - Plasma levels of luteinizing hormone during hyperprolactinemia: response to
      central administration of antagonists of corticotropin-releasing factor.
AB  - Since high concentrations of prolactin (PRL) enhance the hypothalamic release of
      corticotropin-releasing factor (CRF), and CRF decreases the hypothalamic
      secretion of luteinizing hormone (LH)-releasing hormone (LHRH), it could be that
      CRF is involved in the suppressed secretion of LH during hyperprolactinemia. The
      aim of this study was to explore this possibility in hyperprolactinemic male
      rats. Hyperprolactinemia, induced by insertion of 3 pituitary glands under the
      kidney capsule, decreased plasma LH levels by 68% and caused a 2-fold increase in
      plasma corticosterone. Intracisternal administration of the CRF antagonist alpha
      helical CRF(9-41) induced both in pituitary-grafted rats and in
      normoprolactinemic controls a 2 to 3-fold increase of LH in the plasma sample
      taken 1 h after injection of alpha-helical CRF(9-41). Plasma levels of LH in
      pituitary-grafted rats were 2-3 times higher during intracerebroventricular
      infusion for 7 days with CRF antiserum than during saline infusion. Furthermore,
      after infusion of CRF antiserum for 7 days into the lateral brain ventricle
      plasma LH levels had increased by 270% in normoprolactinemic male rats. These
      results indicate that hypothalamic CRF is involved in the control of LH release
      in male rats. To further investigate whether CRF is involved in the effect of PRL
      on LH secretion, we infused PRL, alone or together with CRF antiserum, for 7 days
      into the lateral brain ventricle of normoprolactinemic male rats. After 7 days of
      PRL infusion, LH levels had decreased by 45%, whereas plasma corticosterone was
      150% higher. This action of PRL on LH and corticosterone was prevented when
      besides PRL also CRF antiserum was infused.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731495
TI  - Corticosterone modulates growth hormone-releasing factor and somatostatin in
      fetal rat hypothalamic cultures.
AB  - It is well known that chronic supraphysiological doses of glucocorticoids (GC)
      inhibit GH secretion in vivo, and stimulate GH secretion from the somatotropes in
      vitro. It has been suggested that GC exert an inhibitory role in the hypothalamus
      surpassing the GC-positive effect at the somatotrope level. To test the
      hypothesis that GC can affect growth hormone-releasing releasing factor (GRF) and
      somatostatin (SS) at the hypothalamic level, we studied the effect of
      corticosterone on the immunoreactive content of GRF (IR-GRF) and SS (IR-SS) in
      cells and media of fetal hypothalamic cells in culture. After 20 days in culture,
      cells were incubated with serum-free medium containing corticosterone (from 0.3
      to 300 nM) for 48 h. Corticosterone had a dual effect on IR-GRF. Concentrations
      in the range of the glucocorticoid receptor Kd (3 nM) increased peptide content,
      whereas higher concentrations (30 and 300 nM) decreased IR-GRF content in cells
      and media. Conversely, corticosterone increased SS cell content, only at a
      concentration of 3 nM, inducing a 2- to 3-fold increment in media content with
      the highest doses (30 and 300 nM). These results demonstrated that both GRF and
      SS are modulated by corticosterone in primary fetal rat hypothalamic cultures.
      Whereas GRF exhibited a dual response, stimulatory and inhibitory, at low and
      high corticosterone doses, respectively, SS showed a parallel increase with the
      corticosterone concentrations.

PMID- 7731496
TI  - Central actions of peptide and non-peptide growth hormone secretagogues in the
      rat.
AB  - Evidence for a central site of action of growth-hormone-releasing peptide (GHRP
      6) was sought by (1) counting the number of Fos-positive nuclei within the brain
      following intracerebroventricular or intravenous injection of peptide and non
      peptide GH secretagogues and (2) characterizing the electrophysiological
      responses of neuroendocrine arcuate neurones (recorded in vivo) following
      intravenous injection of GHRP-6. Conscious male rates were chronically implanted
      with intracerebroventricular or intravenous catheters. Dense nuclear Fos staining
      was induced throughout the ventral arcuate nucleus of rats injected
      intracerebroventricularly with low doses of GHRP-6 but not in rats injected with
      the endogenous GH-releasing hormone GHRH or in vehicle-treated controls. The non
      peptidyl GH secretagogues L-692,585 and L-692,429 also induced Fos expression in
      the arcuate nucleus, and the pattern of distribution was similar to that
      described for GHRP-6. No increase in Fos expression was observed in rats given a
      systemic injection of a high dose of GHRH. In pentobarbitone-anaesthetized male
      rats, the effects of intravenous injection of GHRP-6 on the electrical activity
      of arcuate neurones was predominantly excitatory for putative neuroendocrine
      cells and inhibitory for the remaining unidentified cells. These results suggest
      that (1) GHRP-6 and non-peptidyl GH secretagogues have a central site of action
      involving the activation of a subpopulation of arcuate neurones and (2) this
      action is not mimicked by the central or peripheral effects of GHRH.

PMID- 7731497
TI  - Mechanism of action of hexarelin and GHRP-6: analysis of the involvement of GHRH
      and somatostatin in the rat.
AB  - We have recently reported oral and parenteral bioactivity for a new GH-releasing
      peptide, hexarelin. In the present study, we have examined the neuroendocrine
      mechanism by which hexarelin and GHRP-6, two GH-releasing peptides, mediate their
      actions. Although previous studies have looked at the role of growth hormone
      releasing hormone (GHRH) and somatostatin in regulating the action of GHRP-6 in
      culture and in stressed animals, our study looked at the role of both
      somatostatin and GHRH in regulating the action of hexarelin as well as GHRP-6 in
      conscious and freely-moving, nonstressed rats. Adult male rats, prepared with
      indwelling jugular catheters, were pretreated i.v. with either control antiserum
      (CTLas), growth hormone-releasing hormone antiserum (GHRHas), somatostatin
      antiserum (SSas), or both GHRHas and SSas. Animals were then treated i.v. with 25
      micrograms/kg of either hexarelin or GHRP-6 4 h after i.v. antisera pretreatment.
      Blood samples were collected every 20 min for the 3 h prior to peptide treatment
      and at 5, 10, 15, 20, 40 and 60 min following hexarelin or GHRP-6 injection. The
      peak plasma GH responses in rats pretreated with CTLas were 552 +/- 125 ng/ml
      following hexarelin administration and 386 +/- 132 ng/ml following GHRP-6
      administration. Rats pretreated with SSas exhibited peak GH responses following
      hexarelin or GHRP-6 of 702 +/- 115 and 312 +/- 42 ng/ml, respectively. These
      plasma GH responses were similar to those observed in the CTLas-pretreated
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731498
TI  - Modulation of growth hormone-releasing activity of hexarelin in man.
AB  - Hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a new synthetic growth
      hormone (GH)-releasing hexapeptide. The mechanism of action of hexarelin in man
      is not fully elucidated. As for other GH-releasing peptides, an action on both
      the pituitary gland and the hypothalamus has been hypothesized. In the present
      study, we evaluated the modulation of GH-releasing activity of hexarelin in man.
      In a first experiment conducted on 6 healthy male volunteers, we studied the
      interaction of the maximally effective intravenous dose of hexarelin (2
      micrograms/kg i.v.) with GH-releasing hormone (GHRH, 2 micrograms/kg i.v.) and
      somatostatin (2 micrograms/kg/h i.v.). In a second experiment involving another 6
      male subjects, we evaluated the interaction of hexarelin with neuroactive
      substances, such as pirenzepine (0.6 mg/kg i.v.), pyridostigmine (120 mg p.o.)
      and arginine (0.5 g/kg i.v.), thought to modulate endogenous somatostatin
      secretion. Hexarelin induced a higher increase in GH levels as compared to GHRH
      (integrated output calculated as area under the curve AUC0-120 4,693 +/- 691 vs.
      1,494 +/- 102 micrograms.min/l, p < 0.01). Coadministration of hexarelin and GHRH
      produced a higher GH response than hexarelin alone (AUC0-120 7,395 +/- 450
      micrograms.min/l, p < 0.05). Somatostatin abolished the GH response to GHRH (AUC0
      120 363 +/- 89 micrograms.min/l, p < 0.01), while it only blunted that to
      hexarelin (AUC0-120 1,314 +/- 297 micrograms.min/l, p < 0.05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7731499
TI  - Cloning and expression of melanin-concentrating hormone genes in the rainbow
      trout brain.
AB  - Salmonids, a group of tetraploid fish including salmon and trout, produce the
      vertebrate neuropeptide melanin-concentrating hormone (MCH) in a group of
      hypothalamic magnocellular neurons in the nucleus lateralis tuberis (NLT). NLT
      neurons project both to the brain and to the neural lobe of the pituitary gland
      from where MCH is released into the circulation to play a central role in
      camouflage (+/- stress). We have cloned and sequenced the MCH1 and MCH2 genes
      from the rainbow trout, Oncorhynchus mykiss, and used the data firstly to examine
      the position of O. mykiss in salmonid phylogeny, and secondly to enable central
      nervous system MCH1 and MCH2 gene expression to be mapped. In the immature adult
      female trout brain, only MCH2 was detectable at the hybridization stringency
      used. In addition to the known location of MCH-positive neurons,
      immunocytochemistry and in situ hybridization histochemistry revealed a
      previously undescribed nucleus of MCH-positive neurons located more dorsal and
      posterior to those of the NLT, over the paraventricular organ of the lateral
      ventricular recess. Axons from this second group of MCH neurons project dorsally
      into the brain, while a few extend down toward the lateral ventricle near the
      paraventricular organ. They make little, if any, direct contact with the
      neurohypophysis, and thus may subserve a central function, unrelated to hormonal
      colour regulation.

PMID- 7731500
TI  - Thyrotropin-releasing hormone gene expression in cultured anterior pituitary
      cells: role of gender.
AB  - The present studies were undertaken to investigate the effect of gender on
      thyrotropin-releasing hormone (TRH) gene expression in cultured anterior
      pituitary (AP) cells. AP cells derived from 15-day-old male, female, or female
      pups that had been neonatally treated with testosterone propionate (TP), were
      cultured for up to 18 days in a modified DMEM/L-15 medium containing 10% fetal
      calf serum. TRH and AP hormones including GH, prolactin (PRL), luteinizing
      hormone (LH) and thyrotropin (TSH) were measured by RIA, proTRH mRNA was
      determined by in situ hybridization using a full-length riboprobe followed by
      quantification with a computer-assisted image analysis system. Cultures derived
      from female rats contained significantly (p < 0.01) higher amounts of TRH and
      secreted approximately twice (p < 0.01) as much TRH under basal conditions and in
      response to activators of the protein kinase A and C pathways, respectively. In
      situ hybridization studies revealed that 'female' cultures contained
      significantly higher amounts of proTRH mRNA compared to 'male' cultures. Computer
      assisted image analysis demonstrated that proTRH mRNA levels were 3.5 times
      higher in 'female' compared to 'male' cultures (p < 0.01), an effect that was the
      result of a significantly higher number (3 times; p < 0.01) of cells expressing
      proTRH mRNA in 'female' cultures. Neonatal TP treatment did not affect either
      proTRH mRNA or TRH peptide levels. In vitro testosterone treatment resulted in a
      moderate rise (p < 0.05) of intracellular TRH accumulation in cultures from both
      sexes, however, proTRH mRNA levels remained unchanged.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7731501
TI  - Role of neuropeptide Y in the regulation of tyrosine hydroxylase gene expression
      in rat adrenal glands.
AB  - It is well known that the adrenal medulla contains high concentrations of
      neuropeptide Y (NPY) where it coexists with epinephrine and norepinephrine. In
      order to evaluate the possible involvement of NPY in the regulation of the
      chromafin cells of the rat adrenal medulla, we have studied the effects of NPY
      and some NPY analogs on the concentrations of tyrosine hydroxylase (TH) mRNA. The
      following peptides, NPY, PYY, [Leu31, Pro34]-NPY (a Y1 receptor agonist) and
      NPY13-36 (a Y2 receptor agonist) were administered intravenously at the dose of
      40 micrograms/100 g body weight. All the animals were perfused with 4%
      paraformaldehyde 4 h after injection and cryostat sections of adrenals were
      processed for in situ hybridization using a 35S-labelled oligonucleotide probe
      encoding for rat TH. Optical density measurements performed in adrenal medulla
      demonstrated that the administration of NPY, PYY, and [Leu31, Pro34]-NPY induced
      a marked increase in the hybridization signal while the Y2 receptor agonist NPY13
      36 did not affect TH mRNA levels. Then, these data clearly indicate that NPY
      positively regulates the genetic expression of TH probably via the Y1 NPY
      receptor subtype. They suggest that variations in the levels of circulating NPY
      or in the release of NPY by the chromaffin cells themselves (in autocrine and/or
      paracrine way) can increase the biosynthesis of catecholamines in rat adrenals.

PMID- 7731502
TI  - Management of 100 consecutive direct carotid-cavernous fistulas: results of
      treatment with detachable balloons.
AB  - Direct carotid-cavernous fistulas are high-flow shunts with a direct connection
      between the internal carotid artery and the cavernous sinus. The goals of
      treatment are to eliminate the fistula and preserve carotid artery patency. The
      authors reviewed the outcome of 98 patients with 100 consecutive direct carotid
      cavernous fistulas initially treated by transarterial embolization with
      detachable balloons (1979-1992) at the University of Cincinnati Medical Center to
      evaluate the merits of this technique and to provide a standard for comparison
      with future treatment alternatives. Among 100 fistulas, 76 were traumatic in
      origin, 22 resulted from a ruptured aneurysm, and 2 were iatrogenic. The most
      common presentations were orbital bruit (80%), proptosis (72%), chemosis (55%),
      abducens palsy (49%), and conjunctival injection (44%). Eighty-eight fistulas
      were successfully occluded in 86 patients with detachable balloon(s), and
      internal carotid blood flow was preserved in 66 patients (75%). Initial attempts
      at balloon occlusion failed in four patients in whom the fistula eventually
      closed spontaneously. Five patients required direct surgery to occlude the
      fistula, and two were treated with nondetachable balloons; one patient died from
      injuries sustained from trauma. The permanent neurological complication rate was
      4%, including cerebral infarction in one patient, frontal intracerebral
      hemorrhage in one patient, and vision loss in another patient. One death occurred
      related to cerebral infarction from a balloon that shifted. Transient ischemia
      occurred in three patients. On the basis of these results, we conclude that
      transarterial embolization with detachable balloons provides a high rate of
      fistula obliteration with low morbidity and is the best initial procedure to
      treat direct carotid-cavernous fistulas.

PMID- 7731503
TI  - Fibrinolytic therapy for acute embolic stroke: intravenous, intracarotid, and
      intra-arterial local approaches.
AB  - To clarify the efficacy and limitations of the intra-arterial local infusion of a
      high-dose fibrinolytic agent for acute embolic stroke, we analyzed the results of
      44 patients and compared them with those of 51 patients treated with intracarotid
      (18 patients) or intravenous (33 patients) infusion therapy. Ten megaunits of
      recombinant tissue plasminogen activator or 24 x 10(4) IU of urokinase were
      administered through a microcatheter placed into or proximal to an embolus for 20
      minutes. When arterial recanalization was not achieved, a second or third
      infusion was performed. The rates of complete and partial recanalization just
      after the local infusion were 52 and 32%, respectively. They were high in middle
      cerebral and basilar artery occlusion and low in internal carotid artery
      occlusion (69, 78, and 20%, respectively). In our use, there was no difference
      between tissue plasminogen activator and urokinase in restoring blood flow. The
      mean time interval from onset to recanalization in patients with middle cerebral
      artery occlusion showing marked improvement was 4.8 hours, and it was 5.8 hours
      with basilar artery occlusion. The size of infarction was reduced, and the
      outcome was good in patients with complete recanalization achieved. The incidence
      of hemorrhagic infarction within 24 hours was 22%, and only one patient
      clinically deteriorated. In the intracarotid infusion group (20 x 10(4) IU of
      urokinase for 30 min), only two patients showed partial recanalization without
      clinical improvement. The incidence of hemorrhagic infarction was 28%. The
      outcome in this group and the intravenous infusion group (18 x 10(4) IU of
      urokinase a day for 1 wk) was poor compared with that in the local infusion group
      showing complete recanalization. This preliminary study appears to suggest that
      intra-arterial local fibrinolytic therapy could be a new strategy for acute
      embolic stroke.

PMID- 7731504
TI  - Dissecting aneurysms of the basilar artery.
AB  - Ten patients (six men and four women; mean age, 40 yr) with spontaneous
      dissection of the basilar artery are reported. Clinically, six were admitted with
      subarachnoid hemorrhage (SAH) and four were admitted with brain stem ischemia.
      Angiography demonstrated string sign in four patients, pearl reaction in four,
      double lumen in one, and arterial ectasia with mural retention of contrast medium
      in one. Magnetic resonance imaging was performed in two patients. Follow-up
      angiograms or magnetic resonance angiography in six patients showed spontaneous
      healing in two patients, improvement in two, progression in one, and no change in
      one. Nine patients were treated medically, and one underwent selective
      intravascular occlusion of the dissecting aneurysm. One patient died after
      further SAH, two remain severely disabled, three have residual neurological
      deficit, and four are in good clinical condition. The most interesting
      observations in this series include a relatively good course in a substantial
      number of patients and low further bleeding potential after SAH, the late
      "globular" evolution, which may be favorable for reconstructive treatment, and
      the diagnostic value of associated computed tomographic/angiographic findings.
      Surgical options in basilar dissection are very poor; in some reported cases,
      wrapping has been tried with disappointing results. In light of the possibility
      of spontaneous healing or improvement, wrapping should be reserved for only those
      patients with recurrent SAH or angiographic progression of the dissection.

PMID- 7731505
TI  - Pediatric pituitary adenomas.
AB  - Previous series of pediatric pituitary adenomas have been small and have not been
      analyzed by age group. We analyzed the frequency, manifestation, course, and
      biology of these tumors before, during, and after puberty in 136 children younger
      than 20 years old at surgery, identified by review of 2230 patients treated from
      1969 to 1993. Tumors were classified by clinical phenotype. Adrenocorticotropic
      hormone-releasing adenomas were most common before puberty, and prolactinomas
      were most common during and after. The frequencies of adrenocorticotropic hormone
      releasing adenomas, prolactinomas, and endocrine-inactive adenomas differed from
      those in adults. Growth arrest was common with all types except growth hormone
      (GH)-releasing adenomas; menstrual irregularities were common with all but
      adenomas causing Nelson syndrome. Among girls with prolactinomas, the
      preoperative duration of primary amenorrhea was longer than that of other
      symptoms. Tumor size differed by adenoma type. Serum hormone levels shortly after
      surgery correlated with the recurrence of prolactinomas and GH-releasing
      adenomas. The prolactinoma size correlated with the maximum preoperative serum
      prolactin level; boys had larger tumors and higher preoperative and postoperative
      prolactin levels. We conclude that pediatric pituitary adenomas vary in size, age
      at symptom onset, and frequency before, during, and after puberty. Most adenomas
      can cause menstrual irregularities, and primary amenorrhea should prompt
      investigation of the sella. Growth arrest is common with all adenomas except GH
      releasing adenomas. Serum prolactin and GH levels measured at 1 to 5 days after
      surgery indicate the risk of recurrence of prolactinomas and GH-releasing
      adenomas, respectively.

PMID- 7731506
TI  - Intracranial meningiomas in the 9th decade of life: a retrospective study of 17
      surgical cases.
AB  - The general availability of cerebral computed tomographic and magnetic resonance
      imaging scans makes the observation of symptomatic intracranial meningiomas in
      very elderly patients (aged 80 yr or more) relatively frequent. A few authors
      have reported on patients who have undergone surgery for intracranial meningiomas
      in their 9th decade of life, without providing indications regarding the surgical
      criteria and the prognostic factors. We report on a series of 17 patients who
      have received surgery for intracranial meningiomas in their 9th decade of life,
      with the goal of determining some surgical criteria for general physicians and
      neurosurgeons. Patients with severe systemic disease and definite functional
      limitations (American Society of Anesthesiology Class III) had a major
      postoperative morbidity (P = 0.020) and mortality (P = 0.005), especially if they
      scored low (< 70) on the preoperative Karnofsky Rating Scale (P = 0.010). The
      risk of postoperative morbidity was higher when the maximum diameter of the tumor
      was > 5 cm (P = 0.031).

PMID- 7731507
TI  - Comparison of stereotactic radiosurgery and brachytherapy in the treatment of
      recurrent glioblastoma multiforme.
AB  - The purpose of this study was to compare the efficacy of stereotactic
      radiosurgery (SRS) and brachytherapy in the treatment of recurrent glioblastoma
      multiforme (GBM). The patients had either progressive GBM or pathologically
      proven GBM at recurrence after previous treatment for a lower grade astrocytoma.
      Thirty-two patients were treated with interstitial brachytherapy, and 86 received
      treatment with stereotactic radiosurgery (SRS). The patient characteristics were
      similar in the two groups. Those patients treated with SRS had a median tumor
      volume of 10.1 cm3 and received a median peripheral tumor dose of 13 Gy. Patients
      treated with brachytherapy had a median tumor volume of 29 cm3. Median dose to
      the periphery of the tumor volume was 50 Gy delivered at a median dose rate of 43
      cGy/hour. Twenty-one patients (24%) treated with SRS were alive, with a median
      follow-up of 17.5 months. Median actuarial survival, measured from the time of
      treatment for recurrence, for all patients treated with SRS was 10.2 months, with
      survivals of 12 and 24 months being 45 and 19%, respectively. A younger age and a
      smaller tumor volume were predictive of better outcome. The tumor dose, the
      interval from initial diagnosis, and the need for reoperation were not predictive
      of outcome after SRS. Five patients (16%) treated with brachytherapy were alive,
      with a median follow-up of 43.3 months. The median actuarial survival for all
      patients treated with brachytherapy was 11.5 months. Survivals of 12 and 24
      months were 44 and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731508
TI  - Biodistribution of boron sulfhydryl for boron neutron capture therapy in patients
      with intracranial tumors.
AB  - The biodistribution of boron sulfhydryl (BSH) was evaluated for boron neutron
      capture therapy of brain tumors. A selective boron delivery to the neoplasm is a
      prerequisite for successful therapy. The uptake of BSH after intravenous
      administration was analyzed in neoplastic and normal tissues in 61 patients
      undergoing craniotomies for intracranial tumors. The patients received 10 to 100
      mg of BSH/kg (5-50 mg of 10B/kg) body weight, 2 to 72 hours before surgery. The
      tumor boron concentrations ranged from 0.2 ppm (micrograms/g) in a low-grade
      glioma to 19.5 ppm in a high-grade glioma. The tumor to blood boron ratio rose
      above 1 in 15 of 24 high-grade intracerebral tumors, 18 h or more after BSH
      infusion. The boron concentration in high-grade tumors was heterogeneous. Low
      grade intracerebral tumors showed a low boron concentration with a tumor to blood
      ratio below 1. Extracerebral tumors, mainly meningiomas, showed boron
      concentrations comparable with high-grade tumors, with a tumor to blood ratio
      above 1 in 10 of 17 patients. The boron concentrations in skin and muscle
      compared roughly with the blood values. Boron did not enter normal brain in any
      significant amount. In high-grade tumors, tumor to brain ratios were above 2. Low
      boron concentrations in normal brain make BSH safe for a Phase I normal tissue
      tolerance study. Computed tomographic contrast enhancement was evaluated to tumor
      boron uptake for 30 patients. Tumor enhancement on computed tomography does not
      permit the prediction of individual tumor boron concentrations; however, the
      absence of a contrast enhancement was always associated with low boron uptake.

PMID- 7731509
TI  - Radiobiology of radiosurgery for refractory anxiety disorders.
AB  - The neuroradiological manifestations of bilateral single-session gamma (gamma)
      irradiation to normal tissue contained in the internal capsule after gamma knife
      capsulotomy for otherwise intractable anxiety disorders were studied. In nine
      consecutive patients, a target maximum dose of 200 Gy was administered in a
      target volume of 276 +/- 42 mm3 (mean +/- SD) within the 50% isodose level.
      Serial computed tomographic and magnetic resonance imaging scans were undertaken
      from 3 to 44 months after irradiation. After surgery, a necrotic lesion appeared
      on computed tomographic scans, reaching its maximum volume (900 +/- 800 mm3) at 6
      to 9 months, then decreasing (to 457 +/- 400 mm3) over the first postoperative
      year. This volume correlated with the mean isodose level of 91 (range, 41-143)
      Gy. On T2-weighted magnetic resonance imaging scans, the reaction tissue volumes
      were considerably larger and took longer to disappear than expected. In 15
      targets, maximum reaction volumes were recorded at 1 to (approximately) 2 years
      after irradiation. In the remaining seven targets, smaller reaction volumes were
      observed, with no clear maxima appearing during 3 years of observation. In a
      pilot case, a lower target maximum dose of 160 Gy and a radiation volume of 275
      mm3 within the 50% isodose gave only minimal surrounding tissue reactions. This
      report serves to alert clinicians that the tissue reaction volumes and the time
      course of their development after high irradiation doses may be less predictable
      than expected from previous observations in smaller radiation volumes. For this
      reason, lower irradiation doses and smaller volumes should be used in the future,
      and the time factor should be taken into account when interpreting computed
      tomographic and magnetic resonance images of gamma-knife-induced lesions.

PMID- 7731510
TI  - Influence of previous treatment on outcome after glycerol rhizotomy for
      trigeminal neuralgia.
AB  - The aim of the present study was to evaluate the influence of previous treatment
      on outcome and sensory disturbance after a retrogasserian glycerol injection for
      trigeminal neuralgia. Ninety-nine patients with trigeminal neuralgia underwent a
      retrogasserian glycerol rhizotomy. Fifty-three of those patients experienced
      recurrent pain after the previous treatment. At the 1 year follow-up, the outcome
      was excellent or good in 83% of patients with no previous treatment, compared
      with 60 and 75% in those patients with earlier glycerol injections or
      radiofrequency lesions, respectively. Quantitatively assessed, the sensory
      impairment was most pronounced in patients who had earlier radio-frequency
      lesions compared with patients not treated previously. The occurrence of
      dysesthesia was more frequent in patients who had been surgically treated
      earlier. A review of the literature showed that the concentration of the glycerol
      preparation used probably is of great importance in terms of pain relief and
      sensory sequelae.

PMID- 7731511
TI  - Preliminary clinical experience with linear accelerator-based spinal stereotactic
      radiosurgery.
AB  - A prototype device called an extracranial stereotactic radiosurgery frame was
      used to deliver stereotactic radiosurgery, with a modified linear accelerator, to
      metastatic neoplasms in the cervical, thoracic, and lumbar regions in five
      patients. In all patients, the neoplasms had failed to respond to spinal cord
      tolerance doses delivered by standard external fractionated radiation therapy to
      a median dose of 45 Gy (range, 33-65 Gy/11-30 fractions). The tumors were treated
      with single-fraction stereotactic radiosurgery with the spinal stereotactic frame
      for immobilization, localization, and treatment. The median number of isocenters
      was one (range, one to five) with a median single fraction dose of 10 Gy (range,
      8-10 Gy) with median normalization to 80% isodose contour (range, 80-160%). There
      has been a single complication of esophagitis to date from radiosurgery of a
      tumor involving the C6-T1 segments; the esophagitis resolved with medical
      therapy. Median follow-up in this group of patients has been 6 months (range, 1
      12 mo). To date, there has been no radiographic or clinical progression of the
      treated tumor in any patient. Two patients have died from systemic metastatic
      disease. In the three surviving patients, there has been computed tomographic- or
      magnetic resonance-documented regression of the treated tumor with a decrease of
      thecal sac compression with a median follow-up of 6 months (range, 3-14 mo).
      These five patients represent the first clinical application of stereotactic
      radiosurgery in the spine. The results suggest that extracranial radiosurgery may
      be suitable for the treatment of paraspinal neoplasms after external fractionated
      radiation therapy, even in the face of spinal cord compression.

PMID- 7731512
TI  - Three-dimensional computed tomographic angiography in the preoperative evaluation
      of cerebrovascular lesions.
AB  - Although three-dimensional computed tomographic angiography was developed as a
      screening tool for use in patients with suspected cerebrovascular disease, this
      imaging modality has also proven to be of value in surgical planning for patients
      with large or unusual vascular lesions of the brain. The three-dimensional images
      generated by this technique yield valuable information regarding the size and
      configuration of intracranial aneurysms and vascular malformations, the presence
      and extent of intra-aneurysmal thrombus, the relationship of the vascular lesion
      to other cerebrovascular or skeletal structures, aneurysm wall thickness, and the
      presence and orientation of an aneurysm neck. The use of three-dimensional
      computed tomographic angiography in representative cases of patients with large
      or unusual cerebrovascular lesions is presented. It has been our experience that
      this imaging modality displays anatomical information that is not readily
      available from standard, intra-arterial angiography, provides better detail for
      surgical planning than magnetic resonance angiography, and is less expensive than
      either of these other imaging modalities.

PMID- 7731513
TI  - Stereotactic puncture and lysis of spontaneous intracerebral hemorrhage using
      recombinant tissue-plasminogen activator.
AB  - We have tested a treatment protocol for intracerebral hemorrhage (ICH),
      consisting of stereotactic insertion of a catheter into the clot, hematoma lysis
      by the injection of a fibrinolytic agent, recombinant tissue-plasminogen
      activator (rt-PA), and closed system drainage of the liquefied clot. Fourteen
      patients underwent computed tomographically guided stereotactic hematoma puncture
      and silicone tube insertion within 72 hours of intracerebral hemorrhage. The
      majority (nine patients) suffered from ganglionic ICH, and the size of the
      hematoma ranged between 3 x 3 x 4 cm and 7 x 7 x 4 cm (mean, 5.2 x 4 x 3.6 cm).
      All patients had major neurological deficits with or without an impaired level of
      consciousness, but without signs of transtentorial herniation. The initial, then
      daily, dose (in milligrams) of rt-PA administered via the silicone tube equalled
      the maximal diameter (in centimeters) of the original and remaining clot as
      measured initially, then daily, by computed tomographic scan. The number of rt-PA
      injections was four in one patient, three in eight patients, two in four
      patients, and one in one patient, and the total dose of rt-PA required ranged
      from 5 to 16 mg (mean, 9.9 mg). After rt-PA injection, the tubing was clamped for
      2 hours and then opened to drain spontaneously through a closed system against 0
      cm of pressure. At follow-up 6.6 months (mean) after treatment (ranging from 3 to
      13 months) and according to the Glasgow outcome score, one patient was Grade V,
      four were Grade IV, five were Grade III, two were Grade II, and two had
      died.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731514
TI  - Median nerve somatosensory evoked potentials in cervical syringomyelia:
      correlation of preoperative versus postoperative findings with upper limb
      clinical somatosensory function.
AB  - Median nerve somatosensory evoked potentials (SEPs) were recorded in 30 patients
      with cervical syringomyelia before and after surgery. The different SEP
      components were compared with clinical somatosensory findings. The N13 potential
      (generated in the dorsal horn at C5-C6) was pathological in 85% of the upper
      extremities, or 90% of the patients, and correlated with pain/temperature as well
      as vibration/joint position sense; it was of higher sensitivity in syringomyelia
      than any other clinical symptom or SEP component. P14 (brain stem) and N20
      (postcentral cortex) were less often affected and correlated with only
      vibration/joint position sense. Short-term postoperative clinical or SEP changes
      were most often seen after syringoendoscopy and less often after syringostomy,
      resection of cerebellar tonsils, or tumor extirpation. Alterations of SEPs after
      surgery occurred in more patients (60%) than did changes in clinical condition
      (approximately 27%); there was, however, no general correlation between these
      findings. We conclude that median nerve SEP testing with a proper recording
      technique identifying the different subcortical components is a valuable
      supplement in the pre- and postoperative diagnostic evaluation of syringomyelia
      and is of higher sensitivity than clinical somatosensory examination alone.

PMID- 7731515
TI  - On the site of transcranial magnetic stimulation of the facial nerve:
      electrophysiological observations in two patients after transection of the facial
      nerve during neuroma removal.
AB  - The site of stimulation of the facial nerve after transcranial temporo-occipital
      magnetic stimulation is being controversially discussed, particularly whether the
      nerve is stimulated in the root exit zone in the cerebellopontine angle or
      whether stimulation originates within the bony canal of the facial nerve. In two
      case reports, the neurophysiological findings after the surgical transection of
      the facial nerve during the extirpation of a large acoustic and a facial nerve
      neuroma are presented. In both cases, transcranial magnetic stimulation of the
      facial nerve produced compound muscle action potential 4 and 2 days after the
      dissection of the facial nerve at the internal auditory canal and in the
      supralabyrinthine portion. These findings indicate that the site of stimulation
      in transcranial magnetic stimulation can be located to the course of the facial
      nerve within its bony petrosal canal distal to the external genu.

PMID- 7731516
TI  - Intravenous perflubron emulsion administration improves the recovery of auditory
      evoked potentials after temporary brain stem ischemia in dogs.
AB  - Oxygent, a second-generation perfluorocarbon (Perflubron) emulsion (Alliance
      Pharmaceutical Corporation, San Diego, CA) with superior oxygen delivery
      characteristics and greater stability than previous perfluorocarbon emulsions,
      was evaluated as a cerebroprotective agent in a dog model of partial brain stem
      ischemia. Six dogs were exposed to 20 minutes of isolated brain stem ischemia
      after receiving an intravenous bolus of Oxygent at a dose of 1.5 ml/kg. Brain
      stem auditory evoked potentials (BAEP) and regional cerebral blood flow were
      measured before and during the ischemia and for 5 hours after reperfusion.
      Changes in BAEP in this group were compared with those in four control dogs that
      experienced an identical ischemic period but that did not receive Oxygent. During
      the ischemic period, both control and Oxygent-treated animals experienced a
      dramatic decline in BAEP to under 10% of the baseline value. After reperfusion,
      the BAEP increased in both groups to between 50 and 70% of the baseline. In the
      Oxygent-treated group, the BAEP continued to recover to a final sustained level
      of over 80% of baseline. In contrast, the control animals suffered a drop in BAEP
      to 23% of baseline after the brief postischemic peak. The continued improvement
      in the BAEP in the Oxygent-treated group compared with the control groups
      suggests that Oxygent may be of some value as a protective agent to the brain
      stem during ischemia. This effect may be the result of improved oxygen delivery
      to the brain stem or may be related to other effects of Oxygent, such as
      reduction of reperfusion injury. Results suggest that Oxygent may be useful as a
      cerebroprotectant during cerebrovascular surgeries that require temporarily
      reducing blood flow to the brain stem.

PMID- 7731517
TI  - The characteristics of laser-Doppler flowmetry for the measurement of regional
      cerebral blood flow.
AB  - The fundamental characteristics of laser-Doppler flowmetry (LDF), especially the
      depth of cerebral blood flow (CBF) measurement, have not been widely studied in
      the brain tissue; however, LDF has been widely used in recent clinical and
      experimental studies. We investigated the depth of CBF measurement and other
      characteristics related to the use of LDF in the brain. In an animal experimental
      study, the distribution of laser light and the depth of CBF measurement of LDF
      were measured by using modified LDF probes. CBF in various conditions was also
      measured by the LDF and hydrogen clearance method. Laser light of low output lost
      directivity and was dispersed into a hemispherical form in the brain tissue. The
      depth of CBF measurement was approximately 100 to 400 microns, depending on the
      intensity of the emitted laser light, and was affected by changes of CBF. In the
      physiological condition, the close correlation between the values of CBF by the
      LDF and hydrogen clearance method was obtained. After cardiac arrest, the CBF
      value of LDF did not immediately show a 0 value. LDF has several special
      characteristics, and the sample volume was very small. It is important to pay
      attention to the several special characteristics of LDF.

PMID- 7731518
TI  - In vitro growth inhibition of growth factor-stimulated meningioma cells by
      calcium channel antagonists.
AB  - Studies have shown that a majority of meningiomas contain receptors for platelet
      derived growth factor and epidermal growth factor and that these growth factors
      promote the proliferation of meningioma cells in culture. Although the mechanism
      of action has not been elucidated, intracellular calcium appears to be part of
      the signal transduction mechanism. Because alterations in intracellular calcium
      could interrupt this pathway and decrease cellular proliferation, we investigated
      the effects of calcium channel-blocking agents on the growth of meningioma cells
      in vitro. Primary meningioma cell cultures were established, and the cells were
      characterized by light and electron microscopy and by immunohistochemical
      studies. Then, the cultures were given growth factors and/or various calcium
      channel antagonists, and growth rates were measured. A dose-response decrease in
      cell growth was seen when verapamil, nifedipine, or diltiazem (voltage-dependent
      calcium channel-blocking agents) was added to serum-containing media. Also, these
      drugs blocked the growth stimulation of epidermal growth factor and platelet
      derived growth factor in a similar fashion. Dantrolene, which inhibits the
      release of sequestered intracellular calcium, was also an effective blocker of
      the mitogenic stimulation of these growth factors.

PMID- 7731519
TI  - Plasminogen activator inhibitor-1 in brain tumors: relation to malignancy and
      necrosis.
AB  - Tumor necrosis is a common feature of malignant neoplasms. The pathogenesis of
      tumor necrosis remains poorly documented. Recent evidence has shown a correlation
      between the presence of tumor necrosis and low content of tissue plasminogen
      activator in brain tumors and significantly higher levels of plasminogen
      activator inhibitor-1 (PAI-1) in human glioblastomas. We subjected fresh brain
      tumor tissue samples (n = 197) to an enzyme-linked immunosorbent assay to
      determine PAI-1 content. The results were correlated with the presence of edma
      and necrosis on imaging studies. The samples studied were from normal brain (n =
      10), low-grade gliomas (n = 26), meningiomas (n = 47), acoustic neuromas (n =
      18), glioblastomas (n = 45), metastases (n = 45), and areas of tumor necrosis (n
      = 6). The benign tumor samples (n = 96) had 3.5 times less PAI-1 than did the
      malignant tumors (n = 101). Tumor necrosis samples contained 3.8 times more PAI-1
      than did the nonnecrotic malignant tumor samples (P < 0.000001). The benign
      meningioma samples showed a similar ratio compared with their malignant
      counterparts (0.35 versus 1.59 ng/mg, respectively, P = 0.0004). Regression
      analysis results showed a strong correlation between PAI-1 and necrosis (r =
      0.47, P < 0.0000028) and, to a lesser extent, brain edema (r = 0.26, P = 0.001).
      A negative correlation between PAI-1 and tissue plasminogen activator levels
      almost reached statistical significance (P = 0.07). There was no correlation
      between PAI-1 content and the tumor size, duration of symptoms, or the sex or age
      of the patients. The results of this study indicate that malignant transformation
      is associated with a significant increase in PAlI1 and that PAI-1 may play an
      integral role in the pathogenesis of tissue necrosis, perhaps via the inhibition
      of tissue plasminogen activator and the promotion of microthrombosis.

PMID- 7731520
TI  - Hemifacial spasm caused by contralateral cerebellopontine angle meningioma: case
      report.
AB  - A large meningioma in the cerebellopontine angle manifested itself as a
      contralateral hemifacial spasm. On computed tomographic and magnetic resonance
      imaging scans, the brain stem was markedly displaced and distorted by the tumor.
      After total removal of the meningioma, the hemifacial spasm completely
      disappeared.

PMID- 7731521
TI  - Middle meningeal artery aneurysm associated with meningioma: case report.
AB  - Middle meningeal artery aneurysms are rare. Fewer than 10 true aneurysms and 30
      posttraumatic aneurysms on meningeal vessels have been reported. True meningeal
      aneurysms are associated with tumors, Paget's disease, arteriovenous
      malformations, and trauma. Potential morbidity is demonstrated with hemorrhage
      from true aneurysms as well as from pseudoaneurysms of the meningeal vessels. We
      have described a meningeal artery aneurysm of the vascular pedicle of a convexity
      meningioma and reviewed the literature.

PMID- 7731522
TI  - Angioplasty for symptomatic radiation-induced extracranial carotid artery
      stenosis: case report.
AB  - A patient with cervical lymphoma received chemotherapy and radiation to the neck.
      He later presented with crescendo transient ischemic attacks. Angiography
      demonstrated bilateral cervical carotid stenosis, which was presumed to be the
      result of previous radiation therapy. Percutaneous transluminal angioplasty with
      balloon dilation of the symptomatic lesion resulted in an immediate cessation of
      the patient's transient ischemic attacks. Nine months later, he developed a
      symptomatic cervical carotid stenosis of the contralateral carotid artery, which
      also was treated successfully with angioplasty, resulting in a good clinical
      outcome. The patient has experienced no further ischemic events in the 2 years
      after treatment.

PMID- 7731523
TI  - Subacute enlarging cerebral hematoma from amyloid angiopathy: case report.
AB  - We report the case of a 74-year-old woman who, during a 36-hour period, developed
      progressive, focal neurological deficits and eventual coma associated with a
      spontaneously enlarging intraparenchymal hematoma resulting from cerebral amyloid
      angiopathy. The subacute, progressive enlargement of the hematoma, confirmed by
      serial computed tomographic scans, supports the hypothesis that hematomas enlarge
      in amyloid angiopathy as a result of the replacement of the contractile elements
      of the arterial wall by noncontractile amyloid protein. This interference with
      vasoconstriction, the first phase of hemostasis, may be supplemented by local
      endothelial dysfunction causing alterations in the chemical mediators of
      hemostasis, thereby promoting hemorrhage and hematoma enlargement.

PMID- 7731524
TI  - Delayed intracerebral hematoma caused by traumatic intracavernous aneurysm: case
      report.
AB  - Although delayed intracerebral hematomas from head injury are not uncommon, they
      are extremely rare when they are caused by extradural (extracranial)
      pseudoaneurysms of the internal carotid artery in the cavernous sinus. The case
      of a 33-year-old man who sustained a delayed frontal intracerebral hematoma from
      a traumatic intracavernous aneurysm 32 days after a head injury is presented.
      Posterior frontal base fractures accounted for monocular blindness and injury
      over the anterior siphon of the intracavernous carotid artery, which resulted in
      the formation of a pseudoaneurysm inside the sphenoid sinus. Subsequently, the
      cranial base fractures with secondary defects provided a route for the
      pseudoaneurysm to rupture intracranially and also accounted for intractable
      cerebrospinal fluid rhinorrhea and pneumocephalus after surgical treatment for
      the pseudoaneurysm and the intracerebral hematoma.

PMID- 7731525
TI  - Magnetic resonance image findings of spinal intramedullary abscess caused by
      Candida albicans: case report.
AB  - We present the clinical, serological, and radiological features of a patient with
      a spinal intramedullary abscess caused by Candida albicans. Antimycotic treatment
      was successful, and no neurosurgical approach was necessary.

PMID- 7731526
TI  - Inadvertent use of ionic contrast material in myelography: case report and
      management guidelines.
AB  - A 38-year-old man with chronic low back pain underwent myelography and was
      inadvertently injected with ionic contrast medium. Within minutes, he started
      complaining of muscle spasms in his lower extremities, followed by respiratory
      distress and myoclonus. Immediate intravenous treatment with fluids,
      antihistamines, and supplemental oxygen was started. Within 1 hour after the
      myelogram, he was intubated and paralyzed with a neuromuscular blocking agent.
      Shortly thereafter, he began receiving triple anticonvulsant therapy and a lumbar
      drain was inserted to allow for the evacuation of cerebrospinal fluid.
      Electroencephalographic monitoring, which initially showed that the patient was
      in status epilepticus, subsequently showed no more episodes of seizure activity.
      Massive rhabdomyolysis, renal failure, and metabolic derangement were prevented.
      He was then extubated and regained full consciousness. He was discharged on the
      13th day of hospitalization with mild amnesia and some cognitive dysfunction. A
      review of the literature reveals descriptions of 9 of 15 patients who survived
      similar episodes. We conclude that prompt identification of the contrast medium
      error and prompt intervention are crucial to increase significantly the chances
      of survival. Elective paralysis, anticonvulsant therapy, and cerebrospinal fluid
      drainage are the recommended modes of treatment.

PMID- 7731527
TI  - The endolymphatic sac: microsurgical topographic anatomy.
AB  - The endolymphatic sac is part of the membranous labyrinth; it plays an important
      role in the hearing mechanism. Injury to the endolymphatic sac may, over time,
      severely compromise hearing. The endolymphatic sac is located in a duplication of
      the dura of the posterior aspect of the petrous pyramid and is, therefore, in the
      surgical field of many neurosurgical operations performed on the posterolateral
      cranial base. The endolymphatic sac was exposed bilaterally in 10 anatomic
      specimens; the distance from the center of the sac to the posterior lip of the
      internal auditory meatus and to the XIth nerve in the jugular foramen was
      measured with a caliper. Also measured was the distance between the center of the
      sac and the closest point on the petrous ridge and the distance between that
      point and the petro-sigmoid intersection. The petro-sigmoid intersection was
      defined as the point at which the medial aspect of the sigmoid sinus intersects
      the lateral aspect of the petrous ridge. The dimensions of the sac were also
      recorded. On the average, the sac was found to be 15.7 mm posterosuperior
      (superolateral) to the XIth nerve in the jugular foramen (range, 11.0-18.5 mm)
      and 13.3 mm posterior (lateral) to the internal auditory meatus (range, 10.0-18.0
      mm). The center of the sac was 24.1 mm (mean value) (range, 20.0-28.0 mm) in
      front of the petro-sigmoid intersection at a point 11.5 mm (mean value) (range, 8
      17 mm) below the petrous ridge. The mean width and height of the sac were 3.83
      (range, 2-6 mm) and 3.80 mm (range, 2.5-8 mm), respectively.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7731528
TI  - The use of fabric softener in neurosurgical prosections.
AB  - Cadaver prosections are very important for understanding the anatomy of various
      neurosurgical approaches. Formaldehyde fixation is an often-used, time-tested
      method of preserving cadavers, but it makes dissecting difficult, as tissues are
      rendered very tough and rigid. The alternatives to formaldehyde fixation that are
      currently available to make the tissues soft and more life-like either are time
      consuming or shorten the period of time for which cadavers can be stored. We
      examined the effect of fabric softener (methyl bis [tallow amido ethyl] 2
      hydroxyethyl ammonium methyl sulfate) on formaldehyde-fixed brains to make them
      soft and life-like. The deformability was measured by using a Schiotz ocular
      tonometer. We found that the use of fabric softener makes the brain significantly
      softer (P < 0.005) when compared with a standard diluted formalin solution. We
      also used fabric softener in neurosurgical prosections and found that the brain
      can be made soft enough to be able to retract. In addition, it can be used to
      better demonstrate the planes of tissue cleavage, making it very useful in
      simulating a life-like situation. We conclude that the use of fabric softener is
      a simple, reversible, inexpensive technique of obtaining ideal tissue texture for
      dissection of embalmed cadavers to demonstrate neurosurgical approaches.

PMID- 7731529
TI  - Newly designed bayonet clips for complicated aneurysms: technical note.
AB  - Three newly designed bayonet clips (crankshaft clips) are presented. They were
      designed to occlude aneurysms with irregular necks by using the angle and shank
      portion of a bayonet clip (shank clipping). The new clips have shorter distal
      blades and longer shanks (proximal blades), and the angle portions are bent to an
      angle of smaller degree. These clips are useful particularly for aneurysms
      located in a wider space.

PMID- 7731530
TI  - Victor Horsley (1847-1916)

PMID- 7731531
TI  - Patient outcomes after stereotactic radiosurgery for "operable" arteriovenous
      malformations.

PMID- 7731532
TI  - The endoscopic stylet: technical notes.

PMID- 7731533
TI  - Visuo-spatial short-term recognition memory and learning after temporal lobe
      excisions, frontal lobe excisions or amygdalo-hippocampectomy in man.
AB  - Three groups of neurosurgical patients with temporal lobe excisions, frontal lobe
      excisions or unilateral amygdalo-hippocampectomy were assessed on a computerized
      battery of tasks designed to investigate visuo-spatial short-term recognition
      memory and learning. A double dissociation is reported between deficits of
      pattern recognition memory and spatial recognition memory which were observed in
      the two posterior groups and frontal lobe patients, respectively. In addition,
      both the temporal lobe and amygdalo-hippocampectomy patients were also impaired
      on a delayed matching-to-sample paradigm whilst frontal lobe patients performed
      at an equivalent level to controls. Finally, whilst the impaired performance of
      the three groups was indistinguishable on a test of paired-associate learning,
      quite different patterns of deficit were observed on a test of spatial working
      memory. These results are discussed with reference to recent suggestions that
      visual recognition memory is mediated by a neural system which includes, as major
      components, the inferotemporal cortex, the medial temporal lobe structures and
      particular sectors of the frontal lobe, and are compared to previous findings
      from patients with idiopathic Parkinson's disease and dementia of the Alzheimer
      type.

PMID- 7731534
TI  - Kluver-Bucy syndrome after left anterior temporal resection.
AB  - A 70-year-old right-handed woman developed a complete Kluver-Bucy syndrome
      including psychic blindness, aberrant sexual behavior, hypermetamorphosis,
      aphasia and visual agnosia following left anterior temporal lobectomy for an
      anaplasic oligodendroglioma. MRI showed no argument for a contralateral ischemic
      infarct, tumoral growth or white matter damage. Thus the possibility that a
      unilateral anterior temporal lesion can cause the whole picture of Kluver-Bucy
      syndrome must therefore be considered.

PMID- 7731535
TI  - Lateralized free-association priming: implications for the hemispheric
      organization of semantic memory.
AB  - The organization of semantic memory in intact cerebral hemispheres was examined
      by a free-association priming task. Normal subjects studied a list of word pairs
      where the semantic relations were either coordinate (e.g. saw-axe) or locative
      (e.g. bear-forest). Priming of the word pairs was tested by presenting test cues
      (initial words of the pairs) to the left or to the right visual field. Results
      showed an interaction between visual field and word pair type, suggesting a
      qualitative difference in the semantic organization of the hemispheres.
      Specifically, the results support the view that coordinate relations are
      represented in both hemispheres whereas locative relations are represented mainly
      in the right hemisphere.

PMID- 7731536
TI  - Random generation deficit in alcoholic Korsakoff patients.
AB  - Korsakoff's syndrome often affects "executive" functions [Baddeley, A. Human
      Memory, Theory and Practice, 1990], which in anatomical terms are associated with
      the frontal lobes. However, in a previous study, Wiegersma, S. and de Jong, E.
      [J. clin. exp. Neuropsychol. 13, 847-853, 1991] failed to observe a diminished
      performance on the random generation task, although this task is thought to be
      sensitive to "executive" deficits. In the present study, we sought to replicate
      and clarify these earlier findings of Wiegersma and de Jong with a group of
      Korsakoff patients in whom frontal lobe dysfunction was indicated by a reduced
      performance on fluency tasks. Patients and controls were presented with three
      tasks. Digit span was used as an index of short-term memory capacity; memory
      search and comparison processes were measured with the missing item scan; and the
      randomisation task was used to assess the ability to produce non-routine, random
      sequences. The results showed that the performance of Korsakoff patients declined
      on the randomisation task while short-term retention and scanning were intact.
      Analysis of the responses indicated that the Korsakoff patients are able to
      suppress the dominant response, but have problems in generating and carrying out
      alternative strategies in novel problem situations.

PMID- 7731537
TI  - Fluctuations of perceptual asymmetry across time in women and men: effects
      related to the menstrual cycle.
AB  - Women and men performed the same tachistoscopic chair identification task and
      free-vision face processing task during each of three test sessions. For women,
      the first and third sessions were performed during two successive periods of
      menstruation and the second session was performed during the intervening
      midluteal phase of the menstrual cycle. For men, the three test sessions were
      presented at 2-week intervals. For the chair identification task, there was no
      visual field (hemispheric) asymmetry for men during any of the three test
      sessions. For women, there was a right visual field (left-hemisphere) advantage
      during the second (midluteal) test session, but not during the first and third
      (menstrual) sessions. For the free-vision face processing task, there was a
      robust left-side (right-hemisphere) bias during all test sessions for both women
      and men and no effect of test session for either gender. Results for the
      nonlateralized chair identification task are consistent with the hypothesis that,
      in women, the left hemisphere is more activated during the midluteal phase of the
      menstrual cycle relative to the menstrual phase. Results for the lateralized face
      processing task suggest that hemispheric dominance for specific aspects of
      information processing are less likely to show such phase-related effects.

PMID- 7731538
TI  - Topographic EEG activations during timbre and pitch discrimination tasks using
      musical sounds.
AB  - Successive auditory stimulation sequences were presented binaurally to 18 young
      normal volunteers. Five conditions were investigated: two reference tasks,
      assumed to involve passive listening to couples of musical sounds, and three
      discrimination tasks, one dealing with pitch, and two with timbre (either with or
      without the attack). A symmetrical montage of 16 EEG channels was recorded for
      each subject across the different conditions. Two quantitative parameters of EEG
      activity were compared among the different sequences within five distinct
      frequency bands. As compared to a rest (no stimulation) condition, both passive
      listening conditions led to changes in primary auditory cortex areas. Both
      discrimination tasks for pitch and timbre led to right hemisphere EEG changes,
      organized in two poles: an anterior one and a posterior one. After discussing the
      electrophysiological aspects of this work, these results are interpreted in terms
      of a network including the right temporal neocortex and the right frontal lobe to
      maintain the acoustical information in an auditory working memory necessary to
      carry out the discrimination task.

PMID- 7731539
TI  - Attentional control over language lateralization in dyslexic children: deficit or
      delay?
AB  - Two previous verbal dichotic studies by Kershner and Morton (Neuropsychologia 28,
      181-198, 1990) using the forced-attention methodology (Bryden, Strategies of
      Information Processing, Academic Press, London, 1978) demonstrated that the order
      in which the ears were monitored (LE first or RE first) determined whether
      learning disabled children compared to age-matched nondisabled children were more
      weakly or strongly lateralized. The same technique was used with the addition of
      controls for lateral head and eye movements, specific diagnostic criteria to
      include only phonological dyslexics, IQ and reading level. Dyslexic vs age
      matched comparisons replicated the previous studies. The dyslexics produced a
      weaker REA in the LE first order but a greater number of subjects with a REA in
      the RE first order. Reading-matched comparisons suggested that the order-specific
      reduced REA in the dyslexics may reflect a causal deficit of the disorder,
      whereas the order-specific increase in the number of dyslexic subjects with a REA
      was no different than the reading-matched group, implicating a developmental
      delay. The results suggest that children with dyslexia may suffer from a primary
      attentional impairment in altering the REA. This implicates an underlying
      difficulty of flexible verbal processing in response to the rapidly changing
      cognitive requirements of reading.

PMID- 7731540
TI  - Spatial field advantages for tactile line bisection as a function of hemispheric
      specialisation inferred from dichotic listening.
AB  - Thirty left-ear advantaged (LEA) and 30 right-ear advantaged (REA) right-handed
      subjects performed tactile line bisection (TLB) in left and right spatial fields,
      and at midline. REA subjects were found to perform significantly better in the
      right spatial field than in the left and LEA subjects significantly better in the
      left than in the right. Significant directional deviations were found only at
      midline with the left hand deviating to the right and the right hand to the left.
      These findings suggest that TLB is primarily a spatial task subserved by
      feedforward motor processes and that directional deviations are due to the
      differential scaling of egocentric space.

PMID- 7731541
TI  - Imitating gestures and manipulating a mannikin--the representation of the human
      body in ideomotor apraxia.
AB  - Imitation of meaningless gestures was examined in patients with left brain damage
      (LBD), right brain damage (RBD) and controls. In addition to imitation on the own
      body, patients were asked to replicate the gestures on a life-sized mannikin.
      Manual dexterity was assessed by manipulation of beads, and general visuospatial
      abilities by block-design. LBD patients who displayed apraxia when imitating
      gestures on their own bodies scored dramatically worse than any other group when
      imitation was assessed on the mannikin. By contrast, on block-design and
      manipulation of beads patients with RBD were inferior not only to LBD patients
      without apraxia but also to apractic patients. Analysis of CT scans revealed that
      apraxia occurred with frontal, parietal and deep lesions, and that the impairment
      on the manipulation of the mannikin was present regardless of lesion site. The
      results support the contention that the basic deficit underlying impaired
      imitation of meaningless gestures in apraxia is to be sought at a conceptual
      level. Possibly, patients with apraxia are not able to evoke and represent
      conceptual knowledge about the human body which is necessary for performing the
      apparently simple task of imitating gestures.

PMID- 7731542
TI  - Improvement of left visuo-spatial hemineglect by left-sided transcutaneous
      electrical stimulation.
AB  - The effects of transcutaneous electrical stimulation on left visuo-spatial
      hemineglect, assessed by a visuo-motor exploratory task (letter cancellation),
      were investigated in patients with right hemisphere lesions. In Experiment 1 left
      neck stimulation temporarily improved the deficit in 13 out of 14 patients (93%),
      while stimulation of the right neck had no positive effects, worsening
      exploratory performance in nine patients (64%). Experiment 2 showed that left
      neck stimulation temporarily improved neglect also when head movements were
      prevented by a chin-rest. In Experiment 3, stimulation of both the left hand and
      left neck had comparable positive effects on visuo-spatial hemineglect. These
      results are interpreted in terms of: (1) non-specific activation of the right
      hemisphere, contralateral to the stimulation side; (2) specific directional
      effects of left somatosensory stimulation on the egocentric co-ordinates of extra
      personal space, which in neglect patients are distorted towards the side of the
      brain lesion.

PMID- 7731543
TI  - Affective facial expression in infants with focal brain damage.
AB  - Children are fluent affective communicators by their first birthday. The
      development of affective facial expression in infants with focal brain damage
      thus provides a promising context in which to investigate the developing neural
      substrates of emotions. We examined both positive and negative affective
      expression in 12 infants (6-24 months) with pre- or perinatal unilateral focal
      brain damage (6RHD and 6LHD) and their age- and gender-matched controls. Infants
      were videotaped in free and semi-structured tasks. Interactions were
      microanalytically coded, including the use of FACS. Both normal and babies with
      posterior LHD exhibited the full range of appropriate affective expressions. In
      contrast, infants with posterior RHD showed marked affective impairment to
      positive, but not to negative simulation.

PMID- 7731544
TI  - Apolipoprotein E polymorphism and Alzheimer's disease in eastern Finland.
AB  - Apolipoprotein E is a polymorphic protein defined by three alleles, epsilon 2,
      epsilon 3 and epsilon 4. An increased frequency of the epsilon 4 allele is
      associated with late-onset familial and sporadic Alzheimer's disease (AD). We
      studied 202 Finnish AD patients and 55 age- and sex-matched controls. AD patients
      were divided into four subgroups; sporadic early-onset, sporadic late-onset,
      familial early-onset and familial late-onset disease. We found no significant
      differences in the epsilon 4 allele frequency between the subgroups. However, all
      the subgroups differed in the frequency of epsilon 4 allele detection from the
      controls (P < 0.0001). In the late-onset patients, the age at onset decreased
      from 76 to 69 as the number of epsilon 4 alleles increased from 0 to 2.

PMID- 7731545
TI  - NADPH diaphorase is not inhibited by ethylenediaminetetraacetic acid and is not
      specific for nitric oxide synthase in the choroid plexus of rat and mouse.
AB  - NADPH diaphorase is a histochemical activity which, in formaldehyde-fixed tissue,
      is rather specific for nitric oxide synthase. Recently, it was shown that NADPH
      diaphorase activity is inhibited by ethylenediaminetetraacetic acid (EDTA) in
      neurons but not in the choroid plexus epithelium. The present study, while
      confirming these results, demonstrates that the apparent sensitivity of NADPH
      diaphorase for EDTA reflects only the dependence of malic enzyme, which is used
      as the source of reduced cofactor, on Mg2+ or Mn2+ ions. Furthermore, evidence is
      provided that the apparent EDTA-insensitive NADPH diaphorase activity in the
      choroid plexus reflects the activity of alkaline phosphatase in conjunction with
      NADH diaphorase. Apart from these pitfalls, the use of the indirect, malic enzyme
      based method for NADPH diaphorase was found to cause much higher background
      staining compared to the direct method using NADPH, and is therefore proposed to
      be abandoned.

PMID- 7731546
TI  - Nerve growth factor and neurotrophin-3 enhance neurite outgrowth and up-regulate
      the levels of messenger RNA for growth-associated protein GAP-43 and T alpha 1
      alpha-tubulin in cultured adult rat sensory neurones.
AB  - The effect of nerve growth factor (NGF) and neurotrophin-3 (NT-3) on neurite
      outgrowth was related to the level of mRNA for the growth-associated protein GAP
      43 and the neurone specific alpha-tubulin, T alpha 1, in dissociated cultures of
      adult rat sensory neurones. Treatment with NGF or NT-3 for 3 days enhanced
      neurite outgrowth in a dose-dependent manner and by 7-fold and 5-fold,
      respectively, over control at the highest concentrations used. NGF and NT-3
      elevated the level of mRNA encoding GAP-43 by 2.3-fold and T alpha 1 alpha
      tubulin by 3.2-3.5-fold. The estimated ED50 values were 0.1-0.3 ng/ml for NGF and
      2 ng/ml for NT-3 for both neurite outgrowth and mRNA up-regulation.

PMID- 7731547
TI  - Glutamate and glutamine metabolism in cultured GABAergic neurons studied by 13C
      NMR spectroscopy may indicate compartmentation and mitochondrial heterogeneity.
AB  - Primary cultures of mouse cerebral cortical neurons were incubated for 3 h with
      250 microM [U-13C]glutamate or 250 microM [U-13C]glutamine and 6 mM glucose. 13C
      NMR spectra of cell extracts exhibited distinct multiplets for glutamate,
      aspartate and GABA. Incorporation of label into aspartate can only occur through
      the tricarboxylic acid (TCA) cycle, but as demonstrated by formation of the 3,4
      13C2-isotopomer of GABA and the 1,2,3-13C3-isotopomer of glutamate, these amino
      acids were also to some extent derived from this pathway. Formation of the 1,2
      13C2-(1J1,2 = 50 Hz) and 3,4-13C2-isotopomer (1J3,4 = 50.9 Hz) in aspartate
      occurs exclusively when oxaloacetate (containing 12C) is derived from the second
      turn of the TCA cycle. From [U-13C]glutamine, the 12C containing isotopomers in
      aspartate accounted for 27% of the total label and from [U-13C]glutamate, it was
      less than 10%. When [U-13C]glutamine was the precursor, 36% of the labeled
      glutamate and 52% of the labeled GABA contained 12C incorporated during the first
      turn of the TCA cycle. These numbers decreased to 15 and 30%, respectively when
      [U-13C]glutamate was used. Since glutamine must be converted to glutamate before
      it can enter the TCA cycle as 2-oxoglutarate, appearance of 12C incorporation in
      aspartate should be identical when [U-13C]glutamate and [U-13C]glutamine was used
      as substrates. This was, however, not observed which may be indicative of (1)
      compartmentation of mitochondrial glutamate metabolism or (2) differences in the
      amount of intramitochondrial glutamate derived from external glutamate or
      glutamine.

PMID- 7731548
TI  - Effect of locally infused 2-chloroadenosine, an A1 receptor agonist, on
      spontaneous and evoked dopamine release in rat neostriatum.
AB  - Adenosine has been shown to inhibit dopamine release from striatal slices and
      synaptosomes. Recently, a direct interaction between the adenosine A2 receptor
      and dopamine D2 receptor has been provided. Activation of striatal adenosine A1
      receptors is known to partially inhibit the release of dopamine (DA), but some
      aspects of this mechanism remain unclear. We have studied the participation of
      adenosine A1 receptors in the control of DA release 'in vivo' in awake, freely
      moving rats using microdialysis. To this end, the effects of 2-chloroadenosine (2
      CADO), a non-metabolizable adenosine A1 receptor agonist, were studied on basal
      and stimulated striatal DA release. Basal levels were found to be slightly
      decreased by a maximal concentration of 2-CADO without any changes in DA
      metabolites. Haloperidol stimulated DA release was fully counteracted by 2-CADO.
      However, high K+ (100 mM) or (+)-amphetamine stimulated DA release was not
      altered by 2-CADO. Altogether, these data suggest that adenosine acting through
      A1 receptors possibly localized on striatal dopaminergic nerve terminals can
      block an induced D2 receptor blockade, but not the releasing effects caused by
      (+)-amphetamine and high K+ concentration. It is postulated that the increase in
      DA release by haloperidol is mainly due to an increased firing rate of the DA
      neurons and that A1 receptor activation can block the DA release observed in
      response to the action potential activation of DA nerve terminals.

PMID- 7731549
TI  - Neurogenic flare responses are heterogeneous in superficial and deep layers of
      human skin.
AB  - Infrared thermography and video image analysis were used to compare the
      development of the neurogenic flare response in deep and superficial skin layers.
      Neurogenic vasodilatation was induced by injection or iontophoretic application
      of histamine. Thermograms were recorded every 10 s to evaluate the local warming
      reaction. Color-video image analysis was used for computerized delineation of the
      visible flare. Images derived from video analysis were superimposed to the
      thermograms after linear transformation. The thermal reaction started within 10 s
      simultaneously at 2-5 distinct spots after histamine application at distances of
      4-25 mm from the application site while the flare reaction seemed to spread from
      the application site when it became visible after a delay often exceeding 20 s.
      The visible flare but not the warming reaction was suppressed by topically
      applied local anesthetic (EMLA). Warming at focal spots was also observed during
      post-occlusive hyperemia. About 70% of these spots were identical to those
      activated by histamine. The results indicate that the vascular axon reflex is
      differently organized in different layers of the skin.

PMID- 7731550
TI  - Differential voluntary programming of fingers extensor commands revealed by non
      invasive transcranial magnetic stimulation of the human brain.
AB  - Slightly suprathreshold magnetic stimuli were delivered over the left scalp while
      a normal human subject attended a sensory signal which called for a motor
      response of right fingers in a reaction time paradigm. The cortico-motoneuronal
      systems of the two muscles producing finger extension disclosed a remarkable
      physiological differentiation. Brain magnetic stimulation delivered just before
      the subject's motor response revealed cortico-motoneuronal facilitation for one
      extensor muscle and concomitant inhibition for the other, depending on the verbal
      instructions that had been given to the subject before the experimental trial.
      Thus, during the planning of specific finger manipulatory activities, the motor
      brain systems can achieve significant contrast in the membrane excitatory states
      of the motor cortical pyramidal neurones, even for synergic muscles.

PMID- 7731551
TI  - Listening to Mozart enhances spatial-temporal reasoning: towards a
      neurophysiological basis.
AB  - Motivated by predictions of a structured neuronal model of the cortex, we
      performed a behavioral experiment which showed that listening to a Mozart piano
      sonata produced significant short-term enhancement of spatial-temporal reasoning
      in college students. Here we present results from an experiment which replicates
      these findings, and shows that (i) 'repetitive' music does not enhance reasoning;
      (ii) a taped short story does not enhance reasoning; and (iii) short-term memory
      is not enhanced. We propose experiments designed to explore the
      neurophysiological bases of this causal enhancement of spatial-temporal reasoning
      by music, and begin to search for quantitative measures of further higher
      cognitive effects of music.

PMID- 7731552
TI  - The levels of the antagonistic POU family transcription factors Brn-3a and Brn-3b
      in neuronal cells are regulated in opposite directions by serum growth factors.
AB  - The Brn-3a and Brn-3b proteins are closely related POU family transcription
      factors with generally antagonistic effects on gene expression. We show that
      transfer of ND7 neuronal cells to medium containing either no foetal calf serum
      or low concentrations of serum results in a rise in Brn-3a mRNA levels and a fall
      in Brn-3b mRNA levels, although the precise serum dependence of these two effects
      differ. These effects can be reversed by addition of specific growth factors to
      the medium lacking serum, although not all growth factor treatments which
      suppress the rise in Brn-3a can reverse the fall in Brn-3b levels. These effects
      do not correlate with the effects of each treatment on cellular proliferation
      indicating that they are not simply a consequence of changes in proliferation.
      Interestingly however, treatments which produce a rise in Brn-3a levels also
      induce the outgrowth of neuritic processes. Hence the expression of a
      functionally antagonistic pair of POU factors is regulated in opposite directions
      by treatments with serum growth factors and this is likely to represent one means
      by which such growth factors modulate the gene expression patterns and ultimately
      the behaviour of neuronal cells.

PMID- 7731553
TI  - Effects of low glucose levels on changes in [Ca2+]o induced by stimulation of
      Schaffer collaterals under conditions of blocked chemical synaptic transmission
      in rat hippocampal slices.
AB  - It has been shown previously that hypoxia reduced presumed presynaptic Ca2+ entry
      in area CA1 of rat hippocampal slices, perhaps due to energy depletion in
      presynaptic endings. This would imply that hypoglycaemia also affects presynaptic
      Ca2+ uptake. We therefore studied effects of glucose withdrawal on stimulus
      induced changes in [Ca2+]o in area CA1 of rat hippocampal slices. After blockade
      of synaptic transmission by application of the glutamate receptor antagonists 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX, 30 microM) and L-(+)-2-amino-5
      phosphonovaleric acid (2APV, 30 microM) stimulation of Schaffer collaterals
      resulted in small but significant reductions in [Ca2+]o which could be attributed
      to presynaptic Ca2+ entry. Stimulation of the alveus resulted in somewhat reduced
      Ca2+ signals mediated to a large extent by Ca2+ entry into dendrites and somatas
      of pyramidal cells. Removal of glucose results in an augmentation of the presumed
      presynaptic Ca2+ entry by a factor of 2-3. Decreases in [Ca2+]o induced by
      repetitive stimulation of the alveus were initially augmented and then
      disappeared presumably due to irreversible damage of pyramidal neurones. This
      finding suggests that depletion of ATP alone does not account for the depressive
      effect of hypoxia on presynaptic Ca2+ entry.

PMID- 7731554
TI  - Increased dopamine clearance in the non-lesioned striatum of rhesus monkeys with
      unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) striatal lesions.
AB  - In vivo electrochemistry was used to examine the clearance of locally applied
      dopamine in the caudate nuclei of normal, control monkeys and in the non-lesioned
      and lesioned caudate nuclei of unilateral 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-treated monkeys. Chronoamperometric recordings were
      continuously made using Nafion-coated carbon fiber electrodes in anesthetized
      animals while a calibrated amount of dopamine was pressure ejected from a
      micropipette adjacent (250-300 microns) to the electrode. The dopamine signals
      recorded from the MPTP-lesioned caudate nuclei had a greater amplitude and time
      course than those recorded from both the controls and from the non-lesioned side
      of the treated animals, indicating a loss of high-affinity uptake in the lesioned
      caudate. However, the time course was faster, and the clearance rate greater, in
      signals recorded from the contralateral side of the treated animals when compared
      to control caudate nuclei. This suggests that there is an up-regulation in high
      affinity dopamine uptake in the non-lesioned side of the MPTP-treated animals.
      This change may represent a compensatory mechanism that is attempting to maintain
      a balance in extracellular dopamine levels between the lesioned and non-lesioned
      sides.

PMID- 7731555
TI  - Taurine efflux and cell volume regulation in cerebral cortical slices during
      chronic hypernatraemia.
AB  - Efflux of cellular taurine from pre-loaded cerebral cortical slices incubated in
      hypo- and hyperosmotic media has been studied in normal and chronically
      hypernatraemic rats. Significant differences in transport mechanisms between the
      two groups has been noted. Hyperosmotic media retard efflux in cells from normal
      animals, with associated cell shrinkage, but accelerate efflux in cells from
      hypernatraemic rats, in which cell volumes are well maintained at pre
      hypernatraemic levels. In hypernatraemic rats an anionic component of taurine
      efflux, present in normal animals, is lacking. Conversely, a distinct, calmodulin
      dependent component which in normal rats is stimulated only in hypo-osmotic
      media, is present in both hypo- and hyperosmotically incubated slices from
      hypernatraemic rats, and inhibition of calmodulin-activation leads to cell
      swelling. This altered pattern of efflux and cell volume-regulation persists for
      at least 5 h following recovery from hypernatraemia, but remits by 30 h,
      indicating slow down-regulation of the hypernatraemically activated calmodulin
      dependent efflux pathway and re-expression of anionic taurine transport.

PMID- 7731556
TI  - Segmental localisation of the relays mediating crossed inhibition of hindlimb
      motoneurones from group II afferents in the anaesthetized cat spinal cord.
AB  - We have investigated the location of the spinal neurones mediating crossed
      inhibition from group II afferents. Short latency IPSPs are evoked in hindlimb
      extensor motoneurones by stimulation of specific contralateral limb nerves at
      stimuli sufficient to activate group II muscle afferents. Reversible or
      irreversible interruption of the dorsal columns in the fifth lumbar segment (L5)
      dramatically attenuated the crossed inhibition. It therefore appears that the
      central pathway mediating this crossed inhibition involves an interneuronal relay
      located in the L5 segment or further rostrally. As a consequence of this anatomy,
      the short central latency of the crossed IPSPs suggests that a single
      interneurone is involved.

PMID- 7731557
TI  - The neuroprotective efficacy of ebselen (a glutathione peroxidase mimic) on brain
      damage induced by transient focal cerebral ischaemia in the rat.
AB  - The neuroprotective efficacy of the hydroperoxide scavenger ebselen was assessed
      in a model of transient focal ischaemia that utilises the potent vasoconstrictor
      peptide endothelin-1 to induce temporary occlusion of the middle cerebral artery
      (MCA). Pretreatment with ebselen (10 or 30 mg/kg p.o., 40 min pre-MCA occlusion)
      dose dependently reduced the volume of ischaemic damage assessed 4 h post
      endothelin-1 application in the anesthetised rat. The lower dose of ebselen (10
      mg/kg) resulted in a non-significant 35% reduction in the total volume of
      ischaemic damage compared with the vehicle control. In contrast the higher dose
      of ebselen (30 mg/kg) significantly reduced the volume of ischaemic damage in the
      cerebral hemisphere and cerebral cortex by 48% and 53%, respectively. The marked
      reduction in brain damage achieved with ebselen cannot be attributed to drug
      induced alterations in blood pressure, body temperature or arterial blood gases
      since these physiological variables were closely monitored and were not
      significantly altered by ebselen treatment. Thus ebselen is an effective
      neuroprotective agent against acute focal ischaemic-reperfusion injury.

PMID- 7731559
TI  - The day of the long knives.

PMID- 7731558
TI  - Comparative immunohistochemical study of C1G5F2 antigen and
      myelin/oligodendrocyte glycoprotein (MOG) expression in brain of several animal
      species.
AB  - The localisation of the myelin/oligodendrocyte specific antigen C1G5F2 and the
      myelin/oligodendrocyte glycoprotein (MOG) was studied in parallel in the brain of
      various species throughout the phylogenetic line of vertebrates. This
      immunofluorescence study was performed on unfixed brain sections by using the
      newly described monoclonal antibody C1G5F2 and polyclonal anti-MOG antibody. The
      antigen C1G5F2 is detected from the reptilian class onwards whereas MOG is only
      found in mammals. Both antibodies clearly stained only the myelin sheaths in the
      brain of adult animals. The phylogenetic distribution of the C1G5F2 antigen
      compared to the other well known myelin proteins may indicate that it has a
      specific function during myelination. Moreover, evidence is given that the C1G5F2
      antigen is a new minor myelin protein distinct from the glycoprotein MOG.

PMID- 7731560
TI  - AIDS: advocacy & activism. What about us?

PMID- 7731561
TI  - Assisted living: policy implications for nursing.

PMID- 7731562
TI  - Perceived needs of poststroke elders following termination of home health
      services.

PMID- 7731563
TI  - Innovative gerontological practices as models for health care delivery.

PMID- 7731564
TI  - The new genetics & nursing education.

PMID- 7731565
TI  - President's message: nursing's emerging roles.

PMID- 7731566
TI  - Council of Nursing Practice chair Eloise Balasco testifies before Institute of
      Medicine panel.

PMID- 7731567
TI  - Member of the month profile. Tina D. DeLapp, EdD, RN-C.

PMID- 7731568
TI  - Back to the future.

PMID- 7731569
TI  - Smoking at least as important as "pets" and "travel".

PMID- 7731570
TI  - Take another look at unlicensed personnel.

PMID- 7731571
TI  - Teen Nurse Trainees (TNTs): a valuable experience for long-term care institutions
      and teenagers.

PMID- 7731572
TI  - Orienting nursing students to cost effective clinical practice.

PMID- 7731573
TI  - A learning model to guide research and practice for teaching of elder clients.

PMID- 7731574
TI  - Caring groups: a participative teaching/learning experience.

PMID- 7731575
TI  - Moving toward patient empowerment.

PMID- 7731576
TI  - President's message: this is not over!

PMID- 7731577
TI  - Uninsured for health care, minimally employed, living in a definitely rural
      county.

PMID- 7731578
TI  - Building new partnerships at the point of care.

PMID- 7731579
TI  - Managing along the continuum: a new paradigm for the clinical manager.
AB  - Transformation in health care is challenging the roles of all the participants.
      Clinical service managers are at the point of service and feel the impact of
      these changes in a dramatic way. Learning new roles and behaviors in managing a
      continuum-based approach to care delivery will be essential if the organization
      and its leadership is to thrive in the new health care environment. The task of
      the time for managers is to become learners in the journey toward a new service
      delivery system.

PMID- 7731580
TI  - Payer and provider relationships: the key to reshaping health care delivery.
AB  - Though managed care is customarily thought of as the key point of connectivity
      for payers and providers, reshaping health care delivery requires a strong,
      united relationship between the two. The return to a health-related mission is a
      requirement of the new delivery system, which depends on moving beyond disease
      based care and medical financing. In the future, community health status will be
      a strong indicator of success among payers and providers. Community-centered
      models of care for the underserved are illustrative of the opportunities for
      relationship building and strategic alignment between payers and providers.

PMID- 7731581
TI  - Early lessons from a capitated community-based nursing model.
AB  - The community nursing organization (CNO) demonstration is a three-year Medicare
      program to develop, manage, and evaluate a new capitated, nurse-managed system of
      community and ambulatory care. Since February 1994, four national sites have
      started CNOs. The CNO at Carondelet Health Care in Tucson, Arizona, shares early
      experiences in designing and implementing an exciting new community practice
      model.

PMID- 7731582
TI  - The search for healing: is it possible in contemporary health care?
AB  - Several cases are presented in which the patient received less than optimum care
      and treatment from the current health care delivery system. Nursing interventions
      for these cases are proposed consistent with four nursing roles and functions
      that are necessary to make possible true healing. Patients must not feel that
      obtaining health care is like a business transaction. The real challenge for
      nursing in contemporary health care systems is to maintain a therapeutic
      relationship with patients.

PMID- 7731583
TI  - A case study of nursing case management in a rural hospital.
AB  - This article describes the process of implementing a New England model of case
      management in a rural hospital and the modifications necessary in adapting an
      urban model to a rural setting. Nursing case management at this institution has
      been associated with a decrease in the length of stay by 1.7 days at an estimated
      cost savings of $65,932 for the 16-month study period. Case management has also
      been instrumental in improving quality of care through a program of continuous
      quality improvement and in redesigning the RN role. The vision for the future is
      to extend the nurse case manager role outside the hospital walls to the community
      in a collaborative plan that would bill nursing services through physicians'
      offices.

PMID- 7731584
TI  - Nursing: an economic entity and profitable enterprise.
AB  - The concept of nursing as an economic entity and a profitable enterprise is a
      dramatic shift away from traditional employment structures. A move toward self
      employment, self-interest, and capitalism is proposed, so that nursing may reap
      proper financial rewards.

PMID- 7731585
TI  - Department of Veterans Affairs Medical Center, San Diego, California.
AB  - This article outlines the process and status of implementing self-directed
      nursing leadership teams at the San Diego Veterans Affairs Medical Center.
      Perspectives from a staff nurse and nurse practitioner, clinical specialists,
      nurse managers, and the director of the nursing service contribute to an overview
      of this endeavor. Difficulties of decentralizing management functions within a
      centralized system are discussed, as well as considerations and strategies prior
      to initiating change. Integration of self-directed leadership and total quality
      management principles are explored.

PMID- 7731586
TI  - The changing health care delivery structure: opportunities for nursing practice
      and administration.
AB  - The increase in national health care expenditures has placed great stress on the
      economy and has contributed to a widespread consensus that reform of the health
      care delivery system is necessary. Three interrelated strategies are frequently
      used to cope with the turbulent environment in the health care industry today:
      managed care, hospital merger and acquisition to form integrated health care
      delivery systems, and redefined roles for nurses and other health care workers.
      These strategies have profound implications and will offer great opportunities
      for nursing administrators to foster nursing practice in new and improved systems
      of care delivery.

PMID- 7731587
TI  - Embracing technology: the means to ensure nursing's triumph in the era of
      partnerships.

PMID- 7731588
TI  - Capitation's information imperative.

PMID- 7731589
TI  - Maximizing reimbursement for subacute care.

PMID- 7731590
TI  - Legal update, 1994--Part III.

PMID- 7731591
TI  - Outsourcing: should nursing care?

PMID- 7731592
TI  - Nursing productivity: from data to definition.
AB  - Analysts hesitate to measure human services' productivity because crucial
      elements appear so intangible. Furthermore, during contacts or incremental
      exchanges, servor and served consume emerging products of mutual efforts as they
      are produced. The served, primarily the patient, inputs first a certain physical,
      psychosocial and economic status, then a stream of information and responses. The
      nurse, as the primary, inpatient servor continually present at the site of
      service exchange, personally applies certain professional competencies and
      material resources, schedules others' activities, diffuses technology, and
      gathers records and transmits information. The records nurses generate and/or
      keep can define leading indicators of all these inputs and their
      interrelationships. Thus, their various impacts upon nursing services--in
      general, in individual categories, and in individualized course--can be usably
      quantified. Outcomes, too, are definable through comparisons of actual results
      with common expectations shaped within the process and with the results achieved
      by others. Patient classification and staffing ratios are indicators of
      availability of a requisite variety of resources. Data on errors, recidivism and
      referrals act as reliability measures and also yield data on durability in
      achieving anticipated individual results. On this basis, the author proposes
      graded descriptions of factors conditioning productivity and a formula evaluating
      nursing's contributions to it.

PMID- 7731593
TI  - Monitoring staffing variances and length of stay.
AB  - An approach to efficient, effective utilization of personnel in an emergency
      department is described. Through use of worksheets, productivity can be monitored
      accurately and staffing variance identified easily. Trends relative to holding
      time in the emergency department can assist in planning for timely admission in
      order to assure safe and adequate patient care.

PMID- 7731594
TI  - An instrument for measuring differentiated nursing practice.
AB  - Newman's trilevel model of professional nursing practice specifies the roles of
      staff nurse, team leader and clinician/case manager. Essential elements of the
      roles are time and place orientation, assignment of clients, nursing observation
      and communication and nursing interventions. A pilot study to establish validity,
      clarity and fit of items was administered to three groups of nurses to fit the
      trilevel model categories through assessment of their job descriptions.
      Percentage of response indicated the instrument's ability to differentiate the
      roles.

PMID- 7731595
TI  - The P.A.R.T. system: perfecting actual recording talent.
AB  - A comprehensive charting process has been developed to streamline charting
      through increased efficiency. Duplication of patient information is eliminated
      and appropriate teaching is ensured by necessitating that it be documented.

PMID- 7731596
TI  - A continuous quality improvement effort.
AB  - A new method of delivering patient care was implemented on a Critical Care Unit
      when it was discovered that a large percentage of patients required respiratory
      care. A task force redesigned staffing to include a Respiratory Care Practitioner
      (RCP) and a patient/housekeeping aide. It was found that 67% of tasks could be
      delegated to RCPs, so an intensive inservice concentration on delegating skills
      was provided for all.

PMID- 7731597
TI  - The "ups" and "downs" of getting published.
AB  - One stumbling block to writing is the variety of emotional reactions a
      prospective author must negotiate: the "ups" and "downs" of publishing. An
      impressive publishing track record does not necessarily mean an author will avoid
      anxiety, self-doubt or the fear of rejection. A conceptual schema outlines the
      phases in the publishing process and the associated potentially problematic
      emotional reactions.

PMID- 7731598
TI  - An approach to elderly incontinence.
AB  - At least 10 million adults in the U.S. suffer from urinary incontinence,
      including at least half of all nursing home residents. The annual cost is over
      $10 billion and the psychosocial burden is enormous. Nursing can play an
      important role in reducing incidence and continuance of this condition by early
      identification, thorough assessment and appropriate intervention.

PMID- 7731599
TI  - Care-planning in long term care.
AB  - A comprehensive nursing care plan was revised to streamline documentation within
      a long-term care environment, often a "paper tiger" arena. The care plan guides
      certified nursing assistants to prevent and identify resident problems while
      delivering safe care. Not only are separate care protocols identified, but the
      care plan explains the specific nursing interventions to alleviate the residents'
      concerns or problems.

PMID- 7731600
TI  - A case-mix classification system for long-term care facilities.
AB  - The resident assessment and associated classification model inherent in any case
      mix classification system are particularly germane to nursing. Resource
      Utilization Groups-Version III (RUG-III) illustrates how a case-mix
      classification system for long-term care nursing facilities is designed and
      constructed. Understanding the RUG-III classification system can assist nurses in
      evaluating other classification systems that may be adopted by Medicaid programs.
      Nurses provide a crucial perspective in forming and informing healthcare policy
      associated with nursing home payment and quality.

PMID- 7731601
TI  - Uncommon decency: a case study in collegiality.

PMID- 7731602
TI  - Changing the healthcare system from top to bottom.

PMID- 7731604
TI  - Forming a multi-institutional preceptor network.

PMID- 7731603
TI  - Maximizing efficiency of blood specimen collection.

PMID- 7731605
TI  - Testing collective bargaining assumptions.

PMID- 7731606
TI  - TQI: blending the old with the new.

PMID- 7731607
TI  - Comrade healthcare worker...?

PMID- 7731608
TI  - Adverse drug reactions.

PMID- 7731609
TI  - Fee splitting and fees for referrals.
AB  - Both constitute misconduct by the unwary dentist. Understanding what they are and
      how to avoid them can help prevent costly mistakes.

PMID- 7731610
TI  - Financial retirement assets. An objective and subjective analysis.
AB  - Retirement has always been "around the corner" for older dentists. What is new is
      a longer life expectancy, due mainly to advances in nutrition, exercise and
      disease prevention. Many dentists are naturally concerned about the adequacy of
      their retirement assets for a longer life span. This paper helps each dentist
      determine for himself/herself how much of a retirement nest egg is needed, by
      presenting the objective and subjective aspects of their financial holdings.

PMID- 7731611
TI  - Congenital epulis. A case report.
AB  - Congenital epulis is a rare benign tumor found in newborns. A female infant born
      with a congenital epulis is described. The tumor received conservative surgical
      management. Three-year follow-up showed normal dental and alveolar bone
      development.

PMID- 7731612
TI  - Dental education for New York State residents. A 25-year experience.

PMID- 7731613
TI  - Dentistry in the changing benefits market.
AB  - America appears to be moving inexorably toward managed medical care. Where does
      that leave dentists? By not joining in the movement they run the risk of losing
      out altogether. Organized dentistry hopes to provide an answer through its bid
      for legislation to allow its members to compete fairly in the ever-changing
      health care marketplace.

PMID- 7731614
TI  - Treatment of mesially impacted mandibular second molar. A case report.
AB  - A 16-year-old female presented to the author's office for orthodontic treatment
      to upright a mesially impacted second mandibular molar. The tooth was surgically
      exposed. Using a super elastic NiTi archwire, the molar was uprighted in 10
      months of treatment.

PMID- 7731615
TI  - Prescription bleaching agents may damage restorations.

PMID- 7731616
TI  - Smokers fare poorly in oral health studies.

PMID- 7731617
TI  - SPET quality control: a comprehensive test procedure for evaluating the rotation
      system parameters COR-offset, y-shift and detector tilt.
AB  - This paper describes a method for SPET quality control that facilitates the
      determination of COR-offset, parallel y-shift and detector tilt by means of a
      single, comprehensive test using a special phantom consisting of three point
      sources. The evaluation of the method was performed by a series of measurements
      utilizing manually adjusted detector tilts and a simulation of y-shift by moving
      the phantom. The results show that y-shift and detector tilt are measured with
      reasonable accuracy, and that y-shift caused by variations in detector tilt can
      be differentiated from y-shift caused by other factors.

PMID- 7731618
TI  - A turnover study in the male rat of plasma-bound 59Fe, 114Inm and 109Cd with
      particular reference to the gonad.
AB  - After intravenous doses of the plasma-bound radionuclides 59Fe, 114Inm and 109Cd,
      only a minute percentage localizes in the rat testis and remains largely
      unchanged with time. Intratesticular injection of appropriately reduced volumes
      led to much higher proportionate percentage retention of 14, 65 and 11 for 59Fe,
      114Inm and 109Cd, respectively. By this route, significant feedback of the
      elements escaping initial binding was prevented. Distinct but different
      testicular turnovers were now discernible. As a receptor of fluid and spermatozoa
      from the testicular tubules, the epididymis provides an indication of entry into
      and interaction of the metals with spermatogenic cells. For 59Fe no measurable
      changes were detected, whereas a progressive increase in epididymal 114Inm
      occurred, which had not reached a plateau by 70 days. 109Cd, now demonstrated
      within the testicular tubules by autoradiography, remained at constant organ
      level for upwards of 16 days but had declined by 25% by 57 days. At this point,
      the epididymis showed a five-fold increase in the radionuclide, declining to one
      half this value by 126 days. Since 109Cd is carrier free, the data reflect a body
      turnover of dietary cadmium. These results, overall, are compatible with the
      entry of a proportion of each radionuclide into the seminiferous tubules and
      reaction with spermatogenic cells. Possible interpretations of the observed
      differences are presented.

PMID- 7731619
TI  - Scintigraphic detection of infection: are human anti-mouse antibodies a relevant
      problem in immunoscintigraphy with anti-granulocyte antibodies?

PMID- 7731620
TI  - Immunotechnological trends in radioimmunotargeting: from 'magic bullet' to 'smart
      bomb'.
AB  - The impact of recent advances in the chemical and genetic engineering
      manipulations of antibodies on radioimmunotargeting is reviewed both in relation
      to radioimmunoscintigraphy and radioimmunotherapy. The resulting trends are: (1)
      the linking of parts of the mouse/rat and human antibody molecule; (2) the
      creation of molecules with dual antigen or multiple antigen recognition
      capabilities; (3) the making of smaller and smaller antigen recognition
      molecules; and (4) the development of molecules with dual capabilities, e.g.
      antigen recognition and enzyme activity. The various methods of creating
      antibodies in vitro are reviewed with reference to bacteria, using phage
      selection and a combinatorial library, mammalian cells, yeast cells and, finally,
      mice containing giant yeast artificial chromosomes. The advantages and
      disadvantages of smaller fragments as well as of the human anti-mouse antibody
      (HAMA) reaction are discussed and the need for early clinical evaluation and
      widespread availability of the newer antibodies is emphasized. It is envisaged
      that these immunotechnological advances will permit the large-scale production of
      precisely engineered humanized antibodies, and the specificity and affinity rate
      constant of these antibodies can be optimized using in vitro phage selection as
      well as by computer modelling where the stereo chemistry of the antigen is known
      precisely.

PMID- 7731621
TI  - Information as a fundamental attribute among outpatients attending the nuclear
      medicine service of a university hospital.
AB  - The aim of this study was to assess outpatients' satisfaction with the service
      received in the nuclear medicine service of the Hospital Clinic i Provincial of
      Barcelona in February 1993. The patients were randomly assigned to one of two
      groups: group 1 received information about their diagnostic procedure, whereas
      group 2 did not (a control group). A questionnaire was used to assess patients'
      degree of satisfaction. The questionnaire was administered to 803 patients, 243
      (30.26%) of whom completed it and returned it. The following factors were
      significantly related to high scores on the satisfaction scale: age (P < 0.015),
      waiting time (P < 0.001), treatment by assisting personnel (P < 0.001), treatment
      by personnel at the service reception (P < 0.01), waiting room habitability (P <
      0.01), communication variables (P < 0.03) and low scores on the anxiety scale (P
      < 0.02). Group 1 perceived more positively treatment by personnel at reception (P
      < 0.041), treatment by assisting personnel (P < 0.027), waiting room habitability
      (P < 0.035) and communication variables (P < 0.001). The anxiety scale scores
      among this group were significantly lower. We conclude that when information is
      supplied to patients, their anxiety decreases before a diagnostic procedure,
      which significantly improves their perception of the factors that generate
      satisfaction among patients.

PMID- 7731622
TI  - Morphine-augmented versus CCK-augmented cholescintigraphy in diagnosing acute
      cholecystitis.
AB  - Cholescintigraphy was performed after pharmacological manipulation in 60 patients
      with a clinical suspicion of acute cholecystitis and non-visualization of the
      gallbladder 1 h after 99Tcm-DISIDA cholescintigraphy. Thirty patients received an
      intravenous (i.v.) injection of morphine sulphate (group I) and the other 30
      patients an i.v. injection of CCK (group II). The sensitivity, specificity,
      positive predictive value and negative predictive value were 94, 100, 100 and 93%
      in group I and 100, 84, 79 and 100% in group II, respectively. There was a
      significant difference between groups (P < 0.05). In conclusion, morphine
      augmented cholescintigraphy could supply more reliable diagnostic information and
      is less time-consuming in patients with a clinical suspicion of acute
      cholecystitis.

PMID- 7731623
TI  - The value of 99Tcm-MDP bone scans in young patients with exercise-induced lower
      leg pain.
AB  - This study compares the bone scan appearances in 32 patients with medial tibial
      syndrome (MTS) with the appearance in 28 patients with confirmed chronic
      compartment syndrome (CCS). A distinctive pattern of uptake was seen in 30
      patients, 24 of whom had MTS and 6 of whom had CCS. Of the patients with normal
      scans, only 4 had MTS, the remaining 15 had CCS. Both of these findings are
      statistically significant and confirm that bone scans are a useful diagnostic
      tool in the differential diagnosis of exercise-induced lower leg pain.

PMID- 7731624
TI  - Variable portal circulation from inferior mesenteric vein assessed by per-rectal
      radionuclide administration.
AB  - The intrahepatic distribution of radioactivity after the per-rectal
      administration of 201T-chloride and/or 99Tcm-pertechnetate was investigated in
      177 studies in 149 patients with no liver disease or diffuse liver disease and
      compared with that of 99Tcm-stannous (99Tcm-Sn) colloid scintigrams. The patients
      were classified into two groups: distribution of intrahepatic radioactivity of
      201Tl and/or 99Tcm-pertechnetate scintigrams similar to (homogeneous) or
      different from (heterogeneous) that of 99Tcm-Sn-colloid scintigrams. The
      heterogeneous group was divided into three subgroups: increased radioactivity of
      the right lobe (right dominant pattern), increased radioactivity of the left lobe
      (left dominant pattern) and uneven distribution of radioactivity in both lobes
      (uneven pattern). Of the 80 patients in whom the studies were performed in the
      supine position at rest, 14 (17.5%) showed a heterogeneous pattern (8 right
      dominant, 4 left dominant, 2 uneven) and 66 (82.5%) a homogeneous pattern. In the
      97 patients allowed free body movement, 6 (6.2%) showed a heterogeneous (1 right
      dominant, 5 left dominant) and 91 (93.8%) a homogeneous pattern. A significant
      difference in the incidence of heterogeneous distribution between the resting and
      free body movement groups was found (P < 0.05). One patient with a left dominant
      pattern after free body movement with 201Tl showed a right dominant pattern at
      rest in the 99Tcm-pertechnetate study. It is concluded that a heterogeneous
      intrahepatic distribution of inferior mesenteric vein blood is sometimes observed
      and that the distribution of portal vein blood flow seems to be affected by the
      patient's positioning and free body movement.

PMID- 7731625
TI  - Comparison of four alternative radiochemical purity testing methods for 99Tcm
      sestamibi.
AB  - Four different methods for determining the radiochemical purity (RCP) of 99Tcm
      sestamibi have been proposed to replace the recommended thin-layer chromatography
      (TLC) method, as the recommended method is inconvenient and time-consuming. The
      purpose of this study was to compare the recommended TLC method with the four
      proposed rapid QC methods for 99Tcm-sestamibi: (1) chloroform extraction (CE),
      (2) mini-paper chromatography with chloroform/tetrahydrofuran (1:1, v/v) (MPC),
      (3) Waters Sep-Pak alumina N cartridge with 100% ethanol (SPE), and (4) Waters
      Sep-Pak C18 cartridge with normal saline (SPNS). For RCP values ranging from 21.8
      to 98.7% (n = 20), both the CE and SPNS methods produced falsely high RCP values
      (RCP difference: 14.1 +/- 23.5% for CE and 15.0 +/- 24.9% for SPNS). The MPC and
      SPE methods were in good agreement (r = 0.98 for MPC and 0.88 for SPE) with the
      recommended TLC method over the critical RCP range (i.e. 77.0-98.7%, n = 52) (RCP
      difference: -0.9 +/- 1.2% for MPC and -4.3 +/- 3.2% for SPE). None of the 99Tcm
      sestamibi preparations that had been rejected (i.e. RCP < 90%) by the TLC method
      were accepted by either the MPC or SPE method. However, 4 of the 52 99Tcm
      sestamibi preparations with acceptable RCP by the TLC method had unacceptable RCP
      by the MPC method, whereas 8 of the same 52 preparations were unacceptable by the
      SPE method.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731626
TI  - The laboratory evaluation of hypertensive gravidas.
AB  - A number of laboratory tests are available for the evaluation of the hypertensive
      gravida. These tests can be used to either predict and/or prognosticate between
      preeclampsia and other hypertensive disorders of pregnancy. These laboratory
      tests were evaluated based on published experience with special attention to its
      ability to facilitate identification of the patient with preeclampsia apart from
      other hypertensive disorders that co-exist with and occur as a complication of
      pregnancy. Hypocalciuria and increased cellular plasma fibronectin seem to be
      good tests to differentiate preeclampsia from chronic hypertension. The
      management of preeclampsia with its increased risk of perinatal morbidity and
      mortality renders this differentiation clinically very important. Hyperuricemia,
      proteinuria, increased serum beta-thromboglobulin concentration, abnormal red
      blood cell morphology with increased hemoglobin/hematocrit, and increased serum
      iron individually and collectively reflect the severity of preeclampsia.
      Platelets and total serum lactate dehydrogenase are the best tests to reflect the
      severity of HELLP syndrome. Circulating hCG and serum thromboglobulin seem to be
      the most promising future predictors for preeclampsia.

PMID- 7731627
TI  - Etiology of cervical cancer: current concepts.
AB  - The data on the etiological factors presented here may enable us to suggest a
      synergism between the various factors associated with the pathogenesis of
      cervical cancer. Infection of the cervix by HPV 16/18 may result in persistence
      of viral DNA. The persistent HPV-DNA undergoes disruption at the E2 region, when
      integrated into the host genome. The transcriptional products E6 and E7
      oncoproteins bind to and cause the degradation of p53 and Rb tumor-suppressor
      gene products. It is possible that, at that point, other cofactors may be
      involved in the progression toward a precancerous or cancerous condition. Those
      cofactors may include cigarette smoking, by introducing co-carcinogens to the
      tissue or by suppressing the local or systemic immune resistance similar to the
      effect of depressed immune resistance seen in AIDS or immunosuppression of
      transplant patients; hormones, by enhancing growth of HPV and transformation of
      HPV infected cells; low serum vitamin levels leading to decreased tissue
      resistance; or other infections causing local inflammation and the production of
      free radicals. CIN develops, leading eventually to cervical cancer.

PMID- 7731628
TI  - Treatment of vulvar lichen sclerosus in the elderly: an update.
AB  - Lichen sclerosus et atrophicus is a disorder of the skin that can occur anywhere
      on the body and in all age groups but mainly affects middle-aged and elderly
      women in the vulvoperineal area. It consists of ivory or pink papules or macules
      that eventually coalesce into thin, gray, parchment-like areas. Clinically, the
      main symptoms are severe and intractable itching and vaginal soreness with
      dyspareunia. Although it has been described to be associated with an increased
      risk for epithelial malignancy this, in fact, very rarely occurs. The exact
      nature of LSA is still unknown. The accumulation of evidence does little to
      clarify its pathogenesis and etiology. The different reports indicate at least
      three general possibilities; autoimmune, metabolic, and more recently infectious
      etiology. The coexistence of such diverse findings in one disease entity may
      indicate one of the two; either we are facing a group of very similar conditions,
      which will be separated in the future into several closely related clinical
      entities, each with its own etiology, or that all findings represent a complex
      multi-step single pathogenetic mechanism. The latter possibility seems more
      probable because it has previously been suggested that B. burgdorferi, a recent
      prime suspect in the pathogenesis of LSA, may induce both metabolic and
      autoimmune abnormalities in the course of infection. New therapeutic options and
      attitudes emerge that dramatically improved the conservative treatment of this
      disease (Table 5).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731629
TI  - The cerebral palsy story: a catastrophic misunderstanding in obstetrics.

PMID- 7731630
TI  - The length of a short-term contract.

PMID- 7731631
TI  - First aid training: a holistic approach.

PMID- 7731632
TI  - Resuscitation: adult basic life support.

PMID- 7731633
TI  - Wound management: work-induced injuries.

PMID- 7731634
TI  - Contemporary management of breast cancer.
AB  - The diagnosis and treatment of breast cancer have changed dramatically during the
      past two decades. The most important risk factor for breast cancer is advancing
      age; however, 80% of women with breast cancer have none of the currently
      identified risk factors. It is undeniable that early detection and treatment of
      breast cancer reduces morbidity and mortality, and mammography screening is the
      only method available to detect cancer at the earliest stage when it is most
      likely to be cured. Although a number of organizations have recommended breast
      conservation therapy (BCT) as the preferred treatment for early stage breast
      cancer, marked geographic variations in treatment occur. It is suggested that
      appropriate education programs be developed for physicians and women to increase
      familiarity with the selection criteria for BCT and to encourage objective
      discussions of the treatment options during the patient and physician encounter.

PMID- 7731635
TI  - Risk factors.
AB  - Risk factors for breast cancer whose modification would be culturally acceptable
      have not been established. Nearly all women in the United States are at a
      substantial risk for the development of breast cancer. The majority of women,
      however, in whom breast cancer will be diagnosed will live out their lives
      without recurrence of the disease. Newer strategies include prevention and the
      development of effective chemopreventive programs. Phase III clinical trials are
      underway to assess the value of retinoids and tamoxifen. Phase I and II studies
      are underway to assess the potential of more specific treatments to inhibit
      growth factors important in maintaining the malignant phenotype. Obviously, more
      studies are needed to address this major public health problem.

PMID- 7731636
TI  - Mammographic screening of women aged 40 to 49 years. Is it justified?
AB  - Breast cancer among women aged 40 to 49 is of major importance, because about 25%
      of all deaths from breast cancer among women of all age groups occur in women who
      had their breast cancer diagnosed when they were in their 40s. Although mortality
      reduction through screening has been proved in randomized trials for women aged
      50 and older, no single randomized trial has been adequately designed to
      specifically evaluate women aged 40 to 49. Results from seven randomized trials
      and follow-up studies that were not randomized support annual screening of all
      women aged 40 to 49 by mammography, physical examination, and monthly breast self
      examination. If such screening were performed with current state-of-the-art
      mammography, as opposed to the older mammographic techniques used in the trials,
      it is likely that mortality reduction would be substantially greater than that
      found in those trials.

PMID- 7731637
TI  - Making the diagnosis.
AB  - Dramatic changes have occurred in the approach to the diagnosis of breast cancer.
      Increased screening has resulted in the diagnosis of occult lesions, many of
      which represent tumors that are not invasive, and smaller invasive cancers. It is
      now generally accepted that the diagnosis and treatment of breast cancer requires
      a multidisciplinary approach and that open biopsy not only provides the
      histologic diagnosis but also may represent definitive surgical treatment. Thus,
      diagnostic studies should represent the optimal approach to establishing the
      histology of the lesion without compromising later definitive treatment.

PMID- 7731638
TI  - Management of clinically occult (nonpalpable) breast lesions.
AB  - In the past generation, mammography has become a major, if not the best
      available, diagnostic tool for the earlier detection of breast cancer. We have
      certainly come far from hard-to-imagine anecdotes of the early 1970s that "if I
      can't feel it, it's not there!" Although current controversy questions the
      earliest age at which screening mammography truly lowers the death rate from
      breast cancer, that mammography does detect breast cancer years before it might
      be discovered as a mass in the breast cannot be challenged. Mammographic
      techniques have improved so that smaller and smaller areas of suspicion may be
      identified, and mammographers have gained greater judgment in the interpretation
      of these minute radiographic abnormalities. This has inevitably led to an
      increase in procedures designed to explain them. The incurred costs, both
      emotional and economic, of positive mammographic "calls" are considerable.
      Whether practicing medicine as patients' advocates or, as unfortunately currently
      seems to be of equal importance, exercising politically correct and cost
      effective mandates, the management of nonpalpable breast lesions certainly bears
      witness to the correlation of cognitive and procedural skills and cooperation
      between physicians, as well as the technical achievements of contemporary
      medicine.

PMID- 7731639
TI  - Noninvasive breast cancer. The dilemma of the 1990s.
AB  - The most profound impact in the field of breast cancer during the last 15 years
      has been the development and acceptance of screening mammography: a test capable
      of finding nonpalpable cancer years before it would have become clinically
      evident. Many of these nonpalpable lesions are noninvasive; many of them are not
      even real cancers. The spectrum of treatment for noninvasive breast cancer runs
      from nothing more than excisional biopsy to bilateral mastectomy. No wonder
      noninvasive breast cancer is one of the most confusing problems in oncology
      today, for both patients and physicians.

PMID- 7731640
TI  - Invasive breast cancer. Surgical treatment alternatives.
AB  - It is now widely accepted that cancer of the breast is a systemic disease and
      that some patients will not be cured even with the most extensive local
      treatment. This acceptance has resulted in a more conservative approach and
      participation of the patient in treatment planning. A number of factors influence
      the definitive surgical treatment for breast cancer. Important considerations
      include the size and histology of the lesion, the skill and experience of the
      multidisciplinary team, and the wishes of the patient.

PMID- 7731641
TI  - The role of radiation in breast conserving therapy.
AB  - Conservation therapy, consisting of tumor excision followed by irradiation, is an
      accepted alternative to mastectomy for many women with early breast cancer. The
      goals of this treatment approach are tumor control and acceptable breast
      cosmesis. Optimal results require appropriate patient selection and careful
      attention to a number of treatment-related variables.

PMID- 7731642
TI  - Adjuvant therapy in breast cancer.
AB  - Adjuvant therapy has a positive impact in both premenopausal and postmenopausal
      women with primary breast cancer. Some general principles can be used in making
      treatment decisions; however, the precise role of adjuvant treatment in breast
      cancer remains unclear in most clinical settings. Prognostic factors are
      discussed, along with information on uses of chemotherapy and tamoxifen.

PMID- 7731643
TI  - Management of recurrent breast cancer.
AB  - A major challenge for the clinician in treating patients with metastatic breast
      cancer is to achieve the best tumor response with the least toxicity. A number of
      different clinical situations present, and several options for interventions are
      available. In addition, patients with metastatic disease are candidates for newer
      approaches. Currently, intensive chemotherapy with the potential goal of cure has
      been enthusiastically received; however, in most patients, the goal is
      palliation. Achieving this goal requires an understanding of the natural history
      of breast cancer and of the patient and her needs.

PMID- 7731644
TI  - Special problems. Breast cancer and pregnancy.
AB  - Pregnancy-complicated carcinoma of the breast occurs in 3% of patients with
      breast cancer. Breast cancer associated with pregnancy occurs in 3 of every
      10,000 pregnancies. This article provides the background information to allow the
      treating physician to consider the patient's wishes and arrive at a reasonable,
      appropriate, and effective treatment and follow-up plan.

PMID- 7731645
TI  - Breast reconstruction following mastectomy.
AB  - Breast reconstruction after mastectomy for malignant breast disease is a viable
      option that should be offered to all women undergoing mastectomy. Reconstruction
      can be done either at the time of the mastectomy or at any convenient time in the
      postoperative period when the oncologic care givers and the patient feel
      comfortable with the decision. Reconstruction of the breast will not interfere
      with either further therapy or the detection of recurrent tumor. Today more and
      more women who are fully informed about reconstruction opt for the treatment. No
      contraindications to reconstructive surgery arise for the properly selected
      patient.

PMID- 7731646
TI  - Hormonal profiles in women with breast cancer.
AB  - The literature findings on endogenous hormonal profiles in women with breast
      cancer are reviewed in detail. It is concluded that four sets of findings are
      valid: (1) diminished adrenal androgen production, probably genetic, in women
      with premenopausal breast cancer; (2) ovarian dysfunction (luteal inadequacy plus
      increased testosterone production) in breast cancer at all ages; (3) increased 16
      alpha-hydroxylation of estradiol in breast cancer at all ages; and (4) evidence
      that prolactin is a permissive risk factor for breast cancer, and that the
      pregnancy-induced decrease in prolactin levels may account for the protective
      effect of early pregnancy against breast cancer.

PMID- 7731647
TI  - Psychosocial-sexual issues.
AB  - The female breast is discussed in terms of cultural, psychosocial, and sexual
      aspects. These elements are significant in medical and surgical management of
      breast disease and have relevance in the resulting quality of life for female
      patients.

PMID- 7731648
TI  - Medicolegal issues.
AB  - Malpractice claims for failure to diagnose breast cancer are on the increase.
      Obstetrician-gynecologists are frequently targeted as defendants in these claims.
      A significant increase in the frequency and severity of these claims can be
      predicted by virtue of the widespread incidence and severity of the disease,
      coupled with changes in tort law. Physicians can learn risk management and loss
      prevention techniques by studying claims data and actual medical malpractice
      cases.

PMID- 7731649
TI  - Test-retest variability and correlations between tests of texture processing,
      motion processing, visual acuity, and contrast sensitivity.
AB  - PURPOSE: To compare the test-retest variability (reliability) and the relations
      among clinical tests of texture and motion processing, visual acuity for high-
      and low-contrast letters, and the Pelli-Robson contrast sensitivity test.
      METHODS: In 20 normally sighted subjects, monocular visual acuity for letters of
      96% and 11% contrast, Pelli-Robson contrast sensitivity, and motion-defined and
      texture-defined letter recognition thresholds were measured on each of two
      different days. RESULTS: Test-retest correlation coefficients were 0.75, 0.91,
      0.61, 0.90, and 0.84 and bivariate test-retest regression slopes were 1.0, 1.1,
      0.8, 1.0, and 1.2 for high- and low-contrast acuity, contrast sensitivity, and
      motion and texture processing, respectively. The inter-test correlations with
      both test and retest significant were as follows: visual acuity for high-contrast
      letters vs. visual acuity for low-contrast letters; and recognition threshold for
      texture-defined letters vs. acuity for letters of both high and low contrast.
      CONCLUSION: Test-retest variability for the tests of motion and texture
      processing were at least as low as for established clinical tests of high and low
      contrast acuity and contrast sensitivity. We conclude that these new tests offer
      a reliable means of obtaining clinical information which complements that
      provided by conventional tests with luminance-defined letters.

PMID- 7731650
TI  - The relation between invasive and noninvasive tear break-up time.
AB  - TBUT and NITBUT (tear break-up time and noninvasive tear break-up time,
      respectively) were measured on four groups of subjects from different countries
      (two groups of Caucasians, two groups of Chinese). No significant difference was
      found in either TBUT or NITBUT values among the four groups of subjects. Gender
      of the subjects was not a factor affecting the TBUT or NITBUT values. The
      distributions of both NITBUT and TBUT were non-Gaussian and the median value of
      either parameter was lower than those previously reported. The NITBUT values were
      significantly higher than the TBUT values in both Caucasian and Chinese subjects.
      An investigation into the extent of agreement between the TBUT and NITBUT methods
      of assessing tear stability indicated that these methods do not agree
      sufficiently closely (that is, tear stability values measured with the NITBUT
      technique do not agree with those measured with the TBUT technique); short
      average tear break-up values are associated with small differences between the
      measures, whereas long average tear break-up values are associated with large
      differences between the measures.

PMID- 7731651
TI  - Spectral transmittance of UV-absorbing soft and rigid gas permeable contact
      lenses.
AB  - Increasing evidence of acute and chronic ocular effects of ultraviolet (UV)
      radiation has prompted some manufacturers to develop UV-absorbing rigid and soft
      contact lens materials. Currently, eight different lenses containing UV-absorbing
      agents are available in Canada. The spectral transmittance of a sample of these
      UV-absorbing contact lenses was measured in order to determine if all of them
      provide adequate protection from wavelengths in the UV spectrum. The sample
      consisted of 1 lens of each type. Cibasoft Ultrabloc; Permaflex UV; Boston RXD
      and Equalens; Alberta S; FluoroPerm 30, 60, and 92. A Philips single beam
      spectrophotometer was used. The lens under test was placed in a silica wet cell
      filled with unpreserved saline. Spectral transmittance was measured at 0.8-nm
      intervals over the waveband 200 to 800 nm. The results were recorded by a
      microcomputer interfaced to the spectrophotometer. The repeatability of spectral
      transmittance measurements of contact lenses using this method varied between 0%
      and +/- 1.55% of transmission depending on lens material and wavelength studied.
      The results showed that none of the rigid gas permeable (RGP) lenses, except the
      Alberta S, transmitted more than 0.1% (the sensitivity limit of the
      spectrophotometer) up to 380 nm. The Alberta S exhibited transmittance windows in
      the UV spectrum with peaks at 270 nm (23%) and 318 nm (29%). The Cibasoft
      Ultrabloc transmitted less than 1% up to 344 nm, whereas the Permaflex UV had a
      transmittance window in the waveband 240 to 316 nm with a maximum of 17% at 270
      nm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731652
TI  - Differential adherence of Acanthamoeba to contact lenses: effects of material
      characteristics.
AB  - BACKGROUND: Acanthamoeba-associated keratitis occurs most often in contact lens
      wearers. The contact lens material may affect its ability to act as a mechanical
      vector, permitting transfer of viable amoebae from the storage case to the
      corneal surface. The purpose of this study was to investigate the effects of
      ionicity and water content on the comparative quantitative adherence of
      Acanthamoeba trophozoites and cysts to new, unworn hydrogel contact lenses and
      rigid gas-permeable contact lens materials. METHODS: Sixteen quarter segments of
      each of 8 types of unworn hydrogel lenses representative of FDA groups 1 to 4
      were exposed to freshly prepared cultures of either trophozoites or cysts of A.
      castellanii or A. polyphaga for 1.5 h, and then washed. Three types of rigid lens
      button were similarly exposed to A. castellanii trophozoites or cysts. Adherent
      trophozoites and cysts were then enumerated. RESULTS: All hydrogel lenses showed
      binding of both trophozoites and cysts, with the former predominating in every
      case. It was primarily the ionic nature of a lens surface and secondly its water
      content that was associated with increased quantitative adherence of
      Acanthamoeba. Neither form of the amoebae bound to any of the hard lens buttons.
      CONCLUSIONS: Greater relative potential exists for contamination of ionic and
      high-water content hydrogels by Acanthamoeba. This combination may influence
      mechanical transmission of the protozoon to the corneal surface. Adherence to
      hard lenses (as buttons) did not occur if a postincubation wash step was
      performed.

PMID- 7731653
TI  - Idiosyncratic ocular symptoms associated with the estradiol transdermal estrogen
      replacement patch system.
AB  - The Estradiol Transdermal Estrogen Replacement Patch System (Estraderm) is
      designed to provide continuous estrogen replacement therapy through a rate
      limiting membrane applied to the skin. The relative advantage of the patch over
      the more commonly prescribed oral medication, Premarin, is that the drug is
      absorbed directly into the bloodstream without extended metabolism by the
      digestive system and the liver. Ocular side effects associated with Estraderm,
      reported in the literature, include fluctuation in corneal curvature and
      variations of keratitis sicca. Here, a case is presented in which a 50-year-old
      Caucasian female, without previous ocular sequelae status after hysterectomy and
      oophorectomy, experienced what appears to be atypical ocular symptoms associated
      with the Estraderm. To the best of our knowledge, this information has not been
      reported in the literature. Clinicians should be aware of the unusual symptoms
      that could accompany the use of the Estradiol Estrogen Replacement Patch and
      include them among the differential diagnoses. The condition, its associated
      symptoms, and summary of the literature are discussed.

PMID- 7731655
TI  - Statistics notebook: entry IV.C: chi 2 tests.

PMID- 7731654
TI  - Reported myopia in opposite sex twins: a hormonal hypothesis.
AB  - Two studies have reported poor vision in opposite sex twins (evidenced by wearing
      glasses or low visual acuity, both of which are interpreted here as evidence of
      myopia), whereas none have reported an absence of such effects. If these reports
      are replicable, it would suggest a hormonal effect. There is one report of higher
      testosterone levels in those suffering from high myopia. A possible mechanism
      would be if sex hormones in opposite sex pairs transfer from one fetus to the
      other. There is evidence that sex hormones can cross the placenta, and reports of
      sex differences in the development of opposite sex twins are consistent with such
      transfers. If different parts of the eye respond differentially to sex hormones,
      eyes developing in the unusual hormonal environment of opposite sex twins would
      be expected to have high myopia rates.

PMID- 7731656
TI  - Interprofessional strategies for optometry and ophthalmology in the future.

PMID- 7731657
TI  - Three-dimensional organization of cytoskeletons in the vestibular sensory cells.
AB  - The cytoskeletal organization of the guinea pig vestibular sensory cells was
      investigated employing the saponin perfusion method using scanning electron
      microscopy as well as immunohistochemical technique. The intermediate filaments
      were demonstrated in the sensory cells. They were usually seen surrounding the
      nucleus and extending through the cytoplasm which connected the nuclear membrane
      to the plasma membrane, cuticular plate or other cytoorganelles. These findings
      may suggest that the intermediate filaments provide mechanical support to the
      cell and its nucleus. Microtubules were found mainly in the supranuclear portion
      of the cells and run parallel to the main axis of the cell body, which is
      directly connected to the cuticular plate. These findings may suggest that the
      microtubules provide mechanical support to the cell and may be closely related to
      the sensory cell transduction system. The actin filaments were densely packed in
      the site of the cuticular plate. They also distributed throughout the cytoplasm,
      which appeared as a dense network in the periphery region. These findings support
      the idea that the actin filaments could be responsible for sensory cell
      transduction as well as to give mechanical strength to the surface of the cell
      and enable the cell to change its shape and move.

PMID- 7731658
TI  - Alpha-bungarotoxin inhibits outer hair cell motility in situ.
AB  - The effect of two substances (alpha-bungarotoxin, alpha-BGTX, a small protein,
      and the local anesthetic bupivacaine hydrochloride) with an assumed effect on
      outer hair cell (OHC) motility were analyzed after exposing the cochlea via the
      round window membrane. Electrophysiological measurements were performed with a
      very narrow frequency-specific gating (+/- 100 Hz) technique to determine
      auditory brainstem response (ABR) thresholds, including ABR-based frequency
      tuning curves. Exposure to alpha-BGTX gave a minor improvement in thresholds,
      interpreted as a facilitation of OHCs, i.e. releasing their efferent inhibitory
      control, whereas exposure to bupivacaine hydrochloride impaired ABR thresholds,
      possibly due to immobilization of OHC motility via the lateral cell membrane. Our
      results are consistent with the hypothesis that efferent influence on the cochlea
      may be linked with a modulation of the mechanical function of OHCs. We can now
      postulate that there is in vivo evidence that acetylcholine exerts its effect at
      the OHCs via an alpha-BGTX alpha-BGTX binding acetylcholine receptor.

PMID- 7731659
TI  - Cytoskeletal basis for contractility of outer hair cells in the normal adult
      human organ of Corti: comparisons with vestibular hair cells.
AB  - The present study is the first consecutive analysis of the adult normal human
      organ of Corti and vestibular hair cells with regard to the expression of F
      actin, actin-associated proteins (alpha-actinin, alpha- and beta-spectrins,
      vinculin and tropomyosin), beta-tubulin and the calcium-binding protein
      synaptophysin. The expression of these cytoskeletal and their associated proteins
      in man is largely similar to, although not identical with, that previously
      described for several other mammalian species. However, a few very unusual
      staining patterns were found. In several long outer hair cells a rod of F-actin
      extended from the infracuticular area to the cell nucleus. Fluorescence for
      tropomyosin occurred both in the cuticular plates of the outer and inner hair
      cells, and in the area of close apposition between the base of the outer hair
      cell and the apical part of Deiter's cell. In contrast, the vestibular hair cells
      showed immunoreactivity for tropomyosin only in the cuticular plates.

PMID- 7731660
TI  - Microtubule-associated proteins in adult human sensory organs.
AB  - The distribution of microtubule-associated proteins MAP-1 and MAP-2 was analysed
      with immunomorphological techniques in the serially sectioned adult human
      membranous labyrinth. In the organ of Corti, monoclonal antibodies to MAP-1 did
      not stain. Positivity for MAP-2 occurred in the entire outer hair cell cytoplasm,
      in the inner hair cells (?), in the nerve fibres and in the cytoplasm of
      epithelial cells of the spiral prominence. In addition, staining for MAP-2 was
      identified in many (but not all) cells or Reissner's membrane. Immunofluorescence
      for MAP-1 occurred in the supporting cells of the cristae and maculae interpreted
      to be localized in the apical region adjacent to the sensory cells. Thus, the
      distribution of MAP-1 and MAP-2 in the adult human membranous labyrinth was the
      same as described for several animal species with regard to the cochlea. In
      contrast to such a pattern, both MAP-1 and MAP-2 were identified in the human
      vestibular organs, thus identifying a subpopulation of centrally located nerve
      calyces and possibly also the apical portion of vestibular hair cells.

PMID- 7731661
TI  - Hyaluronic acid as a molecular filter and friction-reducing lubricant in the
      human inner ear.
AB  - Immunofluorescence for hyaluronic acid occurred intracellularly in
      morphologically highly specialized areas in the adult human inner ear, for
      instance in the cuticular plates of all types of hair cells, at the apposition
      between outer hair cells and Deiter's cell bodies and in the near-surface area of
      Hensen's cells. The cytoskeletal organization in these regions is characterized
      by tightly packed filamentous proteins. Under physiological stimulus these
      regions undergo micromechanical change, either actively moving (force generation)
      or passively vibrating with changes in elasticity. Hyaluronic acid might
      therefore act as a friction-reducing molecular lubricant. In the lateral wall of
      the cochlea an accumulation of hyaluronic acid occurred in the loose connective
      tissue of the spiral ligament, in particular close to the stria vascularis. Due
      to its complex molecular network, hyaluronic acid offers considerable resistance
      to bulk flow of water and may exclude molecules. The basal cell region of the
      stria vascularis is thus given additional support to minimize (seal?) the stria
      vascularis towards all other areas except the endolymphatic space. Here,
      hyaluronic acid could act as a molecular filter.

PMID- 7731662
TI  - Comparative cytoskeletal analyses of the inner ear in man and the squirrel
      monkey.
AB  - Serially sectioned human and squirrel monkey labyrinths were analyzed with high
      resolution light microscopy after using 25 different monoclonal antibodies (mAbs)
      identifying all three main classes of cytoskeletal proteins. A high degree of
      similarity was found in labyrinths from man and squirrel monkey. Only 1 of 25
      mAbs stained differently between the two species. In the squirrel monkey but not
      in the human the mAbs identifying S-100 proteins stained subpopulations of type I
      vestibular hair cells in the striola of the two macula and the summit of the
      cristae as compared to the same type of hair cells in the periphery of vestibular
      organs. Such an establishment of subpopulations of hair cells with the same
      ultrastructure has previously not been described in higher vertebrates. In
      contrast to the species differences in the distribution of neuroactive
      substances, the cytoskeletal architecture seems to be relatively unchanged and
      stable during evolution. Since each species has its own hearing and equilibrium
      function, neurotransmitters (neuropeptides, amino acids, etc.) could contribute
      to such species-specific functions.

PMID- 7731663
TI  - Calbindin-D28K localization in the primate inner ear.
AB  - The distribution of one of the calcium-binding proteins, calbindin-D28K (CB
      D28K), was studied in the adult human and squirrel monkey inner ear by means of
      immunocytochemical methods. Inner and outer hair cells in the organ of Corti and
      vestibular hair cells showed CB-D28K immunoreactivity, though some vestibular
      hair cells were devoid of immunoreactivity. In the spiral and vestibular
      ganglion, immunoreactive cells were found in both the squirrel monkey and human.
      The present results indicate that CB-D28K is localized within afferent neuronal
      components in these sensory organs and may regulate Ca++ levels for optimal
      neurotransmission in the primate auditory and vestibular systems. This study also
      provides evidence of two nonneuronal localizations of CB-D28K in the squirrel
      monkey. Subpopulations of fibrocytes in the spiral ligament and vestibular end
      organs were enriched with CB-D28K, suggesting that these cells are possibly
      equipped with the function to regulate Ca++ concentration in the perilymphatic
      fluid. In the maculae, many CB-D28K-immunoreactive particles were found in the
      otoconial membrane, indicating that CB-D28K may participate in the formation of
      otoconia.

PMID- 7731665
TI  - Changes needed in adult foster care.

PMID- 7731664
TI  - Health policy: nurses can make a difference at the legislature.

PMID- 7731666
TI  - CNS role continues to evolve in Oregon.

PMID- 7731667
TI  - Are these new models of care?

PMID- 7731668
TI  - [Six-year follow up on recently diagnosed NIDDM patients].
AB  - The six-year prospective data on 100 newly detected NIDDM patients aged 40-69
      years were analysed. After careful and controlled dietetic training, the
      carbohydrate metabolism parameters (glycohaemoglobin, mean blood sugar level and
      glycosuria), the physical status, fundus picture and laboratory data (lipids and
      renal function) were examined yearly and the alterations of the treatment were
      registered. 24 patients dropped out during six years. 10 patients died. The
      carbohydrate status was also favourable and a moderate weight reduction was
      reached. After two years 59% of the patients proved well controlled. At the end
      of six years 41% of the patients were still well controlled merely by dietary
      means. The data were compared with those on 100 similarly detected new NIDDM
      patients whose education and control were provided by family physicians. There
      were non essential differences between the two groups in specific complications,
      BMI and lipids. The level of carbohydrate metabolism control was significantly
      better in the diabetic clinic-controlled patients; the proportion of sulfanylurea
      treated patients was only 40.5% after six years compared with 73% among family
      physicians-controlled patients. The importance of a correct and controlled diet,
      good education and continuous control is emphasized.

PMID- 7731669
TI  - [Estimation of perioperative cardiac risk by means of dipyridamole myocardial
      scintigraphy in patients undergoing vascular surgery on the lower limbs].
AB  - The vascular surgery of lower limbs has an increased cardiac risk that is related
      to the special surgical procedure and the high risk patient population. The
      myocardium scintigraphy after the administration of dipyridamole is a reliable
      stress testing, even despite claudication complaints. The authors performed
      dipyridamole stressed quantitative MIBI scintigraphy in 35 patients with
      peripheral arterial disease for the assessment of prognostic importance of the
      test. Twenty seven of the 29 patients (92%) referred for vascular surgery had a
      positive scintigram. In the two thirds of abnormal investigations (18 patients)
      there had been rest perfusion defects too, despite the fact that only one patient
      had a positive history regarding myocardial infarct (MI). Six cardiac
      complications occurred; all in the aorta crossclamping group (6/21, 29%): 5
      nonfatal postoperative MI (4 of them were silent) and 1 patient died. All of the
      complicated cases showed positive preoperative scintigraphy but only 2 of them
      had stress induced perfusion defect; 4 patients presented fixed defects.
      CONCLUSIONS: 1. Especially the operations necessitating the cross-clamping of
      aorta are harmful. 2. Cardiac complications are frequently atypical in their
      clinical appearance. Thus, 24 and 48 hour after the vascular surgery ECG an
      enzyme investigations are indicated. 3. The fixed MIBI defects that can also be
      found at rest, have significant implications. 4. The most effective cardiac risk
      stratification before vascular surgery is a complex approach in which the
      clinical, ECG and imaging data are incorporated.

PMID- 7731670
TI  - [Helicobacter pylori in benign gastroduodenal diseases].
AB  - (A light- and electronmicroscopic study). We have examined the occurrence of
      Helicobacter pylori (HP) in 2937 gastric antral biopsy specimens from 979
      patients with upper gastrointestinal symptoms. The incidence of HP proved to be
      50.5%. The endoscopic diagnoses were: gastritis (62 cases), gastric erosion
      (425), gastric ulcer (51), duodenitis (22), duodenal erosion (119), duodenal
      ulcer (122) and the HP incidence was 29, 46, 63,, 50, 66 and 73%, respectively.
      Microscopic findings were: chronic gastritis (442), chronic active gastritis
      (356) and normal mucosa (181). The prevalence of HP in these groups was 43%, 78%
      and 11%, respectively. The activity of gastritis was in good correlation with HP
      infection. We did not see epithelial damage, and found only a few instances of
      mucus depletion. Electronmicroscopic examination was performed in order to
      investigate the morphology of bacterium and its relation to the mucosal cells. We
      observed mild loss of microvilli on the cell surface and did not see any cell
      invasion by bacteria.

PMID- 7731671
TI  - [The value of ultrasonic diagnosis in acute appendicitis].
AB  - The diagnostic accuracy and practical value of graded compression ultrasound was
      evaluated in 298 patients admitted for ultrasound examination because of having
      suspected appendicitis by surgeons. The result of the ultrasound was considered
      to be positive, if the inflamed appendix, larger, than 6.5 mm in outer diameter
      or an abscess was depicted. Of the 99 pathologically proven cases of acute
      appendicitis ultrasound was positive in 94, that is the sensitivity was 94.9%.
      The diagnostic accuracy and specificity were 96.3% and 97.9%. The predictive
      value of a positive test was 95.9%, and was 97.5% of a negative one. In the group
      of patients under 18 years (140 patients) sensitivity, specificity and diagnostic
      accuracy were 93.3%, 96.3% and 95% respectively. The use of ultrasound helped
      many patients to earlier operation and reduced considerably the negative
      laparotomy rate. The routine use of ultrasound in the diagnosis of appendicitis
      especially if the clinical presentation is equivocal, complements usefully the
      clinical signs and increases diagnostic accuracy.

PMID- 7731672
TI  - [Childhood acute lymphoid leukemia relapsing in adult age?].
AB  - A 30-years-old woman developed an acute lymphoblastic leukemia 16 years after a
      successfully treated childhood acute lymphoblastic leukemia. The developed second
      malignancy unexpectedly seemed identical to her previous malignant disease.
      That's why and because of the literature doesn't mention acute lymphoblastic
      leukemia as a second neoplasm after an acute lymphoblastic leukemia we considered
      the disease unusual late relaps of the original childhood malignancy.

PMID- 7731673
TI  - [Johannes Marcus Marci (Jan Marek Marci) (1595-1667) the "Prague Hippocrates"].

PMID- 7731674
TI  - [A Hungarian physician-writer in favor of Serbo-Hungarian friendship: Istvan
      Macsai (1823-1889)].

PMID- 7731675
TI  - The biology of Abl during hemopoietic stem cell differentiation and development.

PMID- 7731676
TI  - Androgen suppressed apoptosis is modified in p53 deficient mice.
AB  - Several in vitro studies have provided evidence that the tumor suppressor
      protein, p53, is involved in the cell death process referred to as apoptosis. The
      recent development of p53 knock-out mice has enabled further investigation into
      the function of p53 for apoptosis, in vivo. Radiation-induced apoptosis is
      suppressed in such mice, yet other forms of apoptosis do not seem to be
      significantly affected. In this report, we present evidence that such male p53
      nullizygous mice have less apoptosis in the prostate glands associated with the
      first 4 days following castration. Ventral prostate glands were obtained from
      normal, heterozygous p53-null and p53 nullizygous mice at daily intervals after
      castration. These tissues were stained for apoptosis with the use of the in situ
      and labeling method and apoptotic bodies were quantified by microscopy. Although
      labeled apoptotic bodies were observed in post-castrated tissues from all of
      these genetic variant mice, the onset of apoptosis was delayed and the occurrence
      of apoptosis was significantly reduced in the p53 nullizygous mice when compared
      to normal controls. Heterozygous p53-null mice were intermediate for these
      criteria. Examination of the internucleosomal DNA fragmentation pattern at 2 days
      of castration supports a significant diminution of prostate cell apoptosis in
      nullizygous p53 mice. Additionally, large nucleated and multinucleated cells were
      detected in the prostate epithelium of noncastrated p53 nullizygous mice and
      these abnormal cells were increased after castration. Flow cytometric analysis of
      these tissues confirmed a high number of 4C and 8C DNA content cells in the p53
      nullizygous prostates and their frequency was increased by castration. In
      concordance with an earlier study, we conclude that functional p53 protein is not
      essential for prostate epithelial cells to undergo castration-induced apoptosis.
      However, wild-type p53 does appear to enhance this process, especially in the
      early period following castration, and this protein may regulate an aberrant
      prostate cell cycling activity that follows castration.

PMID- 7731677
TI  - N-terminal 130 amino acids of MDM2 are sufficient to inhibit p53-mediated
      transcriptional activation.
AB  - The human oncoprotein MDM2 binds with the tumor suppressor p53 and inhibits p53
      directed transactivation. In this report we show that deletion of 336 amino acids
      from the C-terminus of human MDM2 does not decrease its efficiency to bind p53 in
      vivo and inhibit p53-directed transactivation. Even further deletion of MDM2 from
      the C-terminus up to amino acid 131 does not reduce its ability to inhibit p53
      mediated transactivation. Since deletion up to amino acid 131 also deletes many
      antigenic sites of MDM2 and the truncated protein cannot be immunoprecipitated by
      the antibodies available to us, two internal deletions were made to define the
      p53-interaction domain. Internal deletion of four amino acids beginning at 110
      residue (amino acids 110 to 113) did not reduce p53-binding or inhibition of p53
      directed transactivation whereas internal deletion of amino acids 60 to 65
      reduces but does not abolish these activities. Sequential deletion of amino acids
      from the N-terminus leads to sequential destruction of p53-binding and inhibition
      of transactivation capability of MDM2. Fourteen amino acids can be deleted from
      this end without any reduction of these activities. Deletion of 28 N-terminal
      amino acids residues drastically reduces, but does not abolish the p53-binding
      ability of the protein, as well as inhibition of p53-directed transactivation.
      Deletion of 58 amino acids from the N-terminus of the oncoprotein abolishes its
      ability to bind p53 in vivo and to inhibit p53-directed transactivation. These
      results locate the p53-binding domain of MDM2 within amino acids 14 to 154 and
      inhibition of transactivation domains of MDM2 within amino acid residues 14 to
      130 suggesting possible p53-independent biological functions of the 491 amino
      acid long oncoprotein.

PMID- 7731678
TI  - Identification of the sites of interaction between c-Raf-1 and Ras-GTP.
AB  - Specific sites of protein-protein interaction were identified in the 51-149
      region of c-Raf-1 using contact epitope scanning and site-directed mutagenesis.
      Nineteen overlapping peptides based upon the primary sequence of the Ras binding
      domain of c-Raf-1 were tested for the ability to competitively inhibit complex
      formation between Ras-GTP and the c-Raf-1 N-terminus. A peptide containing c-Raf
      1 residues 91-105 as well as five overlapping peptides covering a region
      extending from residues 118 to 143 interfered with Ras association, defining
      these sites as potential contact surfaces with Ras. Alanine scanning mutagenesis
      was used as a second probe for sites of Ras interaction with the c-Raf-1 N
      terminus. Raf residues 64-67 and 80-103 were demonstrated as important for
      association with Ras-GTP with residues 66, 67, 84, 87, 89 and 91 identified as
      the most critical individual points of contact with the Ras protein. Alanine
      substitution of residues between 118-143 suggested only one potentially weak site
      of interaction defined by residues 120-125. The combined results of both peptide
      and mutagenic analyses suggest that the primary site of c-Raf-1 interaction with
      Ras maps to Raf residues 80-103, with secondary interactions occurring with
      residues 66 and 67 and possibly 120-125. Contact epitope scanning of the Ras
      effector region found maximum inhibition of Ras/Raf association with a peptide
      corresponding to Ras amino acids 37-51. A model is proposed for the GTP-dependent
      association of Ras and Raf.

PMID- 7731679
TI  - Transformation-restoring factor: a low molecular weight secreted factor required
      for anchorage-independent growth of oncogene-resistant mutant cell lines.
AB  - We have previously described two independent mutant rat fibroblast cell lines
      that fail to form colonies in soft agar when infected with a v-H-ras-expressing
      retrovirus, yet still undergo transformation-related morphological alterations in
      response to this oncogene. We report here that conditioned medium (CM) from non
      transformed rat fibroblasts contains an activity that specifically corrects this
      defect in the mutant cell lines, rendering them capable of anchorage-independent
      growth in response to ras. The major activity in CM, designated transformation
      restoring factor (TRF), is approximately 1300 molecular weight, lipid insoluble,
      and heat, protease, acid and base stable. Latent activity, distinct from TRF, is
      also present in CM; several lines of evidence indicate that transforming growth
      factor (TGF) beta is responsible for this activity. TRF, however, cannot
      substitute for TGF beta in the phenotypic transformation of NRK cells. TRF
      activity is decreased in CM of control cells transformed by ras and this response
      to ras is retained by the mutant cell lines. We propose that whereas wild-type
      cells transformed by ras may constitutively activate a TRF-regulated pathway,
      thus becoming independent of TRF for growth in soft agar, these mutants have
      acquired dependence on an exogenous supply of TRF for this aspect of the
      transformed phenotype. Cellular activities regulated, directly or indirectly, by
      TRF may be effectors of the anchorage-independent growth property that is a
      hallmark of transformed rodent fibroblasts.

PMID- 7731680
TI  - Functional diversity of LIM proteins: amino-terminal activation domains in the
      oncogenic proteins RBTN1 and RBTN2.
AB  - The RBTN1 and RBTN2 genes are activated by distinct translocations involving
      chromosome 11 in some T cell acute leukaemias. The RBTN proteins belong to the
      LIM family which comprises proteins with one, two or three cysteine-rich LIM
      domains, sometimes together with homeodomains or protein kinase domains. The
      RBTN1 and RBTN2 proteins comprise only tandem LIM domains. We report that RBTN1
      and RBTN2 proteins are capable of supporting transcriptional transactivation of
      specific reporter genes in transfection assays. The results, using intact
      proteins or fusions with the homeodomain of the heterologous protein Isl-1, show
      that this transcriptional activation ability resides in the NH2-terminal parts of
      both proteins. The use of yeast assays with RBTN2 shows that RBTN2 forms
      homodimers and that the NH2-terminal 27 amino acids are sufficient to facilitate
      transcriptional transactivation. These data expand the functional diversity of
      the LIM-domain protein family and they augment the previously defined
      relationship between chromosomal translocations and transcriptional activation.

PMID- 7731681
TI  - The expression of the high mobility group HMGI (Y) proteins correlates with the
      malignant phenotype of human thyroid neoplasias.
AB  - High Mobility Group I (HMGI) proteins are nuclear proteins involved in the
      regulation of chromatin structure and function. Elevated expression of the HMGI
      proteins (HMGI, HMGY and HMGI-C) has been correlated with the presence of a
      highly malignant phenotype in epithelial and fibroblastic rat thyroid cells, and
      in several experimental carcinomas. Here, we demonstrate that HMGI and HMGY
      proteins are expressed in human thyroid carcinomas and thyroid carcinoma cell
      lines, but not in adenomas, goiters, normal thyroid tissues and cells. These
      results indicate a correlation between HMGI and HMGY expression and the malignant
      phenotype of thyroid neoplasias, suggesting that these proteins may be used as
      markers in thyroid cancer.

PMID- 7731682
TI  - The PML growth-suppressor has an altered expression in human oncogenesis.
AB  - Altered sub-nuclear localisation of the nuclear body-associated PML protein in
      acute promyelocytic leukaemia, has been proposed to contribute to
      leukaemogenesis. We have recently shown that PML is a primary target gene of
      interferons. Here, it is shown that PML has growth suppressive properties and
      displays an altered expression pattern during human oncogenesis. PML is widely
      expressed in cell-lines and is cell-cycle regulated. Overexpression of the
      protein induces a sharp reduction in growth rates in vitro and in vivo. In
      contrast with cell-lines, in normal tissues (including those that rapidly
      proliferate) only a few cells have detectable PML levels. However, these can be
      upregulated by soluble factors (e.g. IFN, estrogens). Human epithelial tumors
      show a gradual increase of PML levels as the lesion progresses from benign
      dysplasia to carcinoma. A similar induction is found in the surrounding stroma
      and vessels, which likely results from paracrine interactions. Strikingly, when
      malignant cells turn invasive, they loose PML expression, while expression is
      conserved in the stromal compartment. These observations point to the existence
      of a consistent deregulation in the expression of the PML growth-suppressor
      during human oncogenesis.

PMID- 7731683
TI  - Cell cycle arrest by tyrosine kinase Abl involves altered early mitogenic
      response.
AB  - Activated forms of the nuclear and cytoplasmic tyrosine kinase c-Abl are
      completely cytoplasmic and oncogenic. The overexpression of c-Abl, and in certain
      fibroblast cell lines even of v-Abl, leads to a cell cycle arrest revealing an
      alternative Abl function. To facilitate the analysis of this growth inhibitory
      function we have taken advantage of regulable Abl-estrogen receptor (ABL:ER)
      fusion proteins. Oncogenic in the presence of estrogen, they are reversibly
      switched to inhibit cell proliferation upon removal of hormone. Using this
      system, we demonstrate that inhibition is effected by Abl derivatives which we
      have previously shown to be hypo-phosphorylated and to have low kinase activity.
      Since an almost exclusively cytoplasmic ABL:ER protein is fully growth
      inhibitory, relevant interactions may occur in the cytoplasm. We identify the
      cell cycle arrest as an early G1 or G0-like block. Interestingly, growth
      inhibition correlates with an altered expression pattern of early serum response
      genes; c-Jun mRNA and c-Fos protein levels are elevated in Abl-blocked cells. In
      view of the two functional modes of overexpressed Abl proteins, one can speculate
      that normal c-Abl may be involved in relaying growth regulatory signals from the
      membrane to the nucleus.

PMID- 7731684
TI  - Cell type-specific activity of the N-myc promoter in human neuroblastoma cells is
      mediated by a downstream silencer.
AB  - The N-myc oncogene is actively transcribed in many neuroblastoma tumors, but is
      not expressed in mature, normal tissue of any type. Chloramphenicol acetyl
      transferase (CAT) assays of constructs containing N-myc sequence transfected into
      N-myc expressing LA-N-5 neuroblastoma cells or non-expressing HeLa carcinoma
      cells have revealed a 201 base pair (bp) regulatory region mediating the cell
      type-specific activity of the promoter. While located downstream from 5' mRNA cap
      sites, the region appears to function by preventing transcriptional initiation.
      This downstream region is capable of suppressing promoter activity independently
      of position, and contains an element having 100% homology with the 9 bp consensus
      sequence of a transcriptional silencer found in the upstream region of the
      lysozyme gene. DNA gel retardation assays have shown that this sequence is
      involved in a specific DNA-protein interaction with nuclear extract from HeLa
      cells that is distinct from that occurring with extract from LA-N-5 cells. These
      results suggest that the N-myc promoter's cell type-specific activity is
      regulated by a downstream silencer, and that differential binding of regulatory
      protein from that present in non-expressing cells may result in the constitutive
      N-myc expression seen in neuroblastoma.

PMID- 7731685
TI  - Stabilization of cyclin E and cdk2 mRNAs at G1/S transition in Rat-1A cells
      emerging from the G0 state.
AB  - mRNAs for cyclin E and Cdk2 have a role in the commitment to DNA replication in
      the cell cycle, and are induced in Rat-1A cells by serum stimulation. Cyclin E
      and cdk2 genes are transcribed in quiescent cells, but their transcripts rapidly
      turn over and levels are kept low. The rate of transcription of the cdk2 gene is
      slightly increased after serum stimulation, while that of cyclin E is fairly
      constant. At the G1/S transition of serum-stimulated cells, transient
      stabilization of the two types of mRNAs occurs, an event which may lead to
      induction of each mRNA. Artificial expression of an immediate-early protein delta
      FosB results in proliferation of quiescent Rat-1A cells, and this is accompanied
      by an efficient induction of cyclin E and cdk2 mRNAs. In delta FosB-expressing
      cells, two types of mRNAs are stabilized to the same extent seen in serum
      stimulated cells. The expression of cyclin E and cdk2 genes is upregulated by
      stabilization of their transcripts, at least in part. We propose that delta FosB
      may have a role in regulation of progression of the cell cycle in serum
      stimulated Rat-1A cells by triggering stabilization of mRNAs for cyclin E and
      Cdk2.

PMID- 7731686
TI  - The TTG-2/RBTN2 T cell oncogene encodes two alternative transcripts from two
      promoters: the distal promoter is removed by most 11p13 translocations in acute T
      cell leukaemia's (T-ALL).
AB  - The TTG-2 gene has been identified at the site of chromosomal translocations in
      acute T-cell leukemia's (T-ALL). These breakpoints map to a region between 2 and
      30 kb upstream of TTG-2 in chromosome 11p13. To establish the role of these
      translocation breakpoints in the deregulation of TTG-2 in T-ALL we have
      determined the complete structure of this gene. Isolation of new TTG-2 cDNA
      clones from fetal liver identified an alternative transcript (TTG-2a) containing
      two new noncoding 5' exons. Analysis of exon/intron boundaries, identified 6
      exons spread over 35 kb in 11p13. The gene encodes two alternative transcripts
      initiating from two promoters. TTG-2a, from promoter 1 (P1) and TTG-2b, from
      promoter 2 (P2) differ in the length of the 5' untranslated region, but encode
      the same protein. A high level of TTG-2a was present in fetal liver and spleen,
      whereas in adult kidney a low level of TTG-2a and a high level of TTG-2b was
      found. The transcription start site for TTG-2a was identified by RNase protection
      experiments and it displayed sequence homology to an initiator element (inr). P1
      lacks a TATA box, but binding sites for SP1 and GATA-1 are present. This new
      genomic organisation revealed that all known chromosomal translocations map
      upstream of P2, removing P1 and putative upstream regulatory sequences leaving P2
      intact. These results show that chromosomal translocations disrupt the TTG-2 gene
      itself, further confirming its role in the development of T-ALL.

PMID- 7731687
TI  - Two serum response elements mediate transcriptional repression of human smooth
      muscle alpha-actin promoter in ras-transformed cells.
AB  - The mechanism by which activated ras oncogene expression leads to repression of
      genes encoding specific actin filament proteins is not understood. However, these
      changes associated with loss of organized actin filaments, are necessary to
      maintain the transformed phenotype. The human smooth muscle (sm) alpha-actin
      promoter is repressed in ras-transformed fibroblast cells and derepressed in
      revertant cell lines. In this study, we demonstrate that two serum response
      elements (SREs) present in the alpha-actin promoter are required for
      transcriptional repression in ras-transformed cells and the two SREs act
      synergistically to repress heterologous promoters in a ras-transformation
      dependent manner. Serum response factor (SRF), which can bind to the sm alpha
      actin SREs, restores alpha-actin promoter activity in ras-transformed cells. c
      Fos, c-Jun and YY1 also repress alpha-actin promoter through SREs, suggesting
      that these transcription factors may play a role in repressing alpha-actin
      promoter in ras-transformed cells.

PMID- 7731688
TI  - Sequence of the human invasion-inducing TIAM1 gene, its conservation in evolution
      and its expression in tumor cell lines of different tissue origin.
AB  - By means of proviral tagging in combination with in vitro selection for invasive
      T-lymphoma variants, we have previously identified the murine invasion- and
      metastasis-inducing Tiam1 gene. Tiam1 encodes a novel protein which shares a Dbl
      homology (DH) domain with GDP dissociation stimulator-(GDS) proteins that
      activate Rho-like GTPases. We have cloned the human TIAM1 coding sequence and
      studied its evolutionary conservation and expression pattern. TIAM1 is highly
      conserved among vertebrates. The close similarity between human TIAM1 and the
      mouse homologue is indicated by 88% and 95% identity of nucleotides and predicted
      sequences, respectively. The murine gene is highly expressed in brain and testis
      and at low or moderate levels in almost all other normal tissues. Interestingly,
      Tiam1 transcripts were found in virtually all analysed tumor cell lines of human
      and rodent origin including B- and T-lymphomas, neuroblastomas, melanomas and
      carcinomas. The evolutionary conservation as well as the broad expression pattern
      of Tiam1 in most normal tissues, suggests a general function in cellular
      signaling processes presumably by activation of a Rho-like GTPase that regulates
      the cytoskeletal organization.

PMID- 7731689
TI  - Multiple mRNA isoforms of the human RET proto-oncogene generated by alternate
      splicing.
AB  - The RET proto-oncogene encodes a receptor tyrosine kinase. We and others have
      recently shown that distinct germline mutations of the RET proto-oncogene account
      for the majority of cases of the dominantly inherited multiple endocrine
      neoplasia (MEN) type 2 syndromes, and can cause a dominantly inherited form of
      Hirschsprung disease, a disorder of development of the autonomic innervation of
      the gut. RET is also oncogenically activated in some sporadic thyroid and adrenal
      tumours. Here we report the characterisation of multiple mRNA isoforms of RET
      generated by alternate splicing. Two isoforms are predicted to encode membrane
      spanning receptors with a truncated extracellular ligand-binding domain. A third
      isoform is predicted to encode a soluble, secreted form of the receptor. These
      mRNA isoforms are expressed in both normal and tumour tissues.

PMID- 7731690
TI  - The role of immunoglobulin kappa elements in c-myc activation.
AB  - Burkitt's lymphoma cells are characterized by chromosomal translocations
      involving the proto-oncogene c-myc on chromosome 8 and one of the immunoglobulin
      gene loci on chromosome 2, 14 or 22. The translocated c-myc allele is
      transcriptionally activated, shows a preferential usage of promoter P1 over P2
      (promoter shift) and lacks the ability to retain the transcription complex at the
      P2 promoter. In order to define the elements of the immunoglobulin kappa gene
      involved in deregulation of c-myc in a t(2;8) translocation, we designed
      constructs consisting of c-myc and different parts of the immunoglobulin kappa
      gene locus. Chromatin analysis of these stably transfected constructs revealed
      DNase I hypersensitive sites within the c-myc 5' region characteristic for an
      actively transcribed c-myc gene and three sites within the immunoglobulin kappa
      locus corresponding to the matrix attachment region, the intron and 3' enhancers,
      respectively. These three regulatory elements were necessary and sufficient for
      maximal c-myc activation and formation of the promoter shift. Kinetic nuclear run
      on experiments were performed to study the distribution of transcription
      complexes on c-myc exon 1 on constructs with and without the immunoglobulin kappa
      regulatory elements. The absence of a pausing polymerase complex at the c-myc P2
      promoter could be demonstrated for constructs consisting of c-myc and the two
      kappa enhancers. Therefore the two enhancers are sufficient to relief the
      elongational block at the P2 promoter, however, the matrix attachment region is
      additionally required for maximal c-myc activation observed in Burkitt's lymphoma
      cells.

PMID- 7731691
TI  - ErbB-3 mediates differential mitogenic effects of NDF/heregulin isoforms on mouse
      keratinocytes.
AB  - The family of Neu differentiation factors (NDFs, or heregulins) includes a dozen
      secreted glycoproteins, whose receptor binding domain displays two variants,
      alpha and beta, and they bind to two receptor tyrosine kinases, ErbB-3 and ErbB
      4. Certain isoforms were reported to induce growth-arrest and differentiation of
      mammary tumor cells, while other breast cancer cell lines responded
      mitogenically. The present study addressed the biologic effects of various NDF
      isoforms on normal EGF-dependent epithelial cells, Balb/MK keratinocytes, that
      can undergo either proliferation or differentiation. We found that beta isoforms
      of NDF induced a mitogenic effect, that was significantly smaller than the
      maximal response to EGF. By contrast with NDF-beta, NDF-alpha isoforms exerted
      almost no mitogenic effect, but they were sufficient to maintain keratinocytes in
      culture. Consistent with their higher mitogenic potency, NDF-beta isoforms bound
      to Balb/MK cells with higher affinity (Kd = 2.2 nM) than alpha isoforms, however
      both groups shared their receptor, that we identified as ErbB-3. No transcript of
      ErbB-4 was detectable in the keratinocytes, but these cells express multiple NDF
      mRNAs and also ErbB-2. We conclude that different isoforms of NDF induce distinct
      growth regulatory effects on cultured keratinocytes, through direct interaction
      with ErbB-3.

PMID- 7731692
TI  - K-ras gene mutations in early colorectal cancer ... flat elevated vs polyp
      forming cancer....
AB  - K-ras gene mutations in early colorectal cancer were detected by two-step
      sensitive polymerase chain reaction (PCR) and enzyme digestion method. Early
      colorectal cancer was classified into flat elevated cancer or polyp-forming
      cancer according to morphology and presence of adenomatous components. A total of
      60 paraffin-embedded tissue specimens from patients with early colorectal cancer
      were analysed. K-ras codon 12 mutations were detected in 23.3% (7/30) of flat
      elevated cancer and 63.3% (19/30) of polyp-forming cancer. The incidence of K-ras
      codon 12 mutations in flat elevated cancer was significantly lower than in polyp
      forming cancer (P < 0.01). These data suggested that K-ras gene mutations may be
      correlated with morphology or clinical features in flat elevated cancer, and that
      flat elevated cancer may originate from a pathway different from adenoma
      carcinoma sequence.

PMID- 7731693
TI  - Co-amplification of MYCN and a DEAD box gene (DDX1) in primary neuroblastoma.
AB  - DEAD box proteins are putative RNA helicases that have been implicated in
      cellular processes involving alteration of RNA secondary structure, such as
      translation initiation and splicing. These proteins share eight conserved amino
      acid motifs, including Asp(D)-Glu-(E)-Ala(A)-Asp(D) which is part of a more
      extended motif. Recently, we have shown that the novel DDX1 gene containing a
      DEAD box motif maps to the same chromosome band as MYCN at 2p24 and is co
      amplified with MYCN in retinoblastoma cell lines. Here, we show that the DDX1
      gene is co-amplified with the MYCN gene in 2 of three neuroblastoma cell lines
      and that DDX1 RNA levels correlate with DDX1 gene copy number. Since
      amplification of MYCN is an indicator of poor prognosis in neuroblastoma, it was
      of interest to determine whether co-amplification with DDX1 occurred in clinical
      samples of neuroblastoma and whether such a finding carried any additional
      prognostic significance. We determined the gene copy number of DDX1 in 32
      neuroblastoma patient samples (representative of all stages): 13 were MYCN
      amplified and 19 had normal copy numbers of the MYCN gene. Of the 13
      neuroblastomas that were MYCN amplified, seven were also DDX1 amplified. Of the
      19 that were not MYCN amplified, none were DDX1 amplified. This is the first
      example of a gene that is co-amplified with MYCN at a high frequency in
      neuroblastoma. While there was a trend towards a worse clinical outcome with co
      amplification, the numbers were too small to reach significance.

PMID- 7731694
TI  - Human ERG is a proto-oncogene with mitogenic and transforming activity.
AB  - The ETS related gene, ERG, is one of 20 or more genes belonging to the ETS family
      of transcription factors. Translocation of the ERG gene t(21;22) results in the
      chimeric fusion transcript seen in approximately 10% of Ewings sarcomas. In
      addition, recent studies have shown that a reciprocal translocation t(21;16) of
      ERG gives rise to two aberrant transcripts seen in some forms of acute myeloid
      leukaemia. In vitro studies have linked the up regulation of ERG expression with
      stromal cell independence in erythroleukemic clones and shown that the ERG
      related genes ETS1 and ETS2 have a mitogenic and transforming activity when
      overexpressed in NIH3T3 cells. Interestingly ERGB/FLI-1, which is also involved
      in Ewings sarcoma translocations and shares a very high sequence identify with
      ERG has been reported to be unable to transform NIH3T3 cells. In this study we
      investigate the effects of overexpression of ERG on cell proliferation, factor
      dependence, growth in soft agar and tumorigenesis in nude mice. An ERG expression
      construct with the human ERG2 cDNA driven by the sheep metallothionein la
      promoter (sMTERG) was transfected into NIH3T3 cells. Clonal cell lines
      overexpressing ERG were established. The cell lines became morphologically
      altered, grew in low serum and serum free media and gave rise to colonies in soft
      agar suspension. Furthermore, we demonstrate that after subcutaneous injection
      these clones grow as solid tumors in nude mice. These data demonstrate that c-ERG
      is a proto-oncogene capable of transforming NIH3T3 cells. Therefore,
      overexpression or inappropriate expression of ERG may contribute to oncogenesis.

PMID- 7731695
TI  - An intact PDGF signaling pathway is required for efficient growth transformation
      of mouse C127 cells by the bovine papillomavirus E5 protein.
AB  - The bovine papillomavirus type 1 (BPV) E5 protein is a 44 amino acid, membrane
      associated protein that induces growth transformation of cultured rodent and
      bovine fibroblasts. In transformed fibroblasts, the BPV E5 protein activates the
      endogenous platelet-derived growth factor (PDGF) beta receptor, and the
      introduction of the PDGF beta receptor gene into heterologous cell types normally
      lacking PDGF beta receptor expression permits transformation by the E5 protein.
      However, neither the endogenous PDGF beta receptor nor its signaling pathway has
      been shown to be required for efficient growth transformation of fibroblasts by
      the BPV E5 gene. Here we have tested whether the endogenous PDGF beta receptor
      serves as a target for the BPV E5 protein in mouse C127 fibroblasts. We isolated
      variant C127 cell lines that displayed reduced DNA synthesis in response to PDGF
      but a normal response to other mitogens, suggesting that they harbor specific
      defects in the PDGF signaling pathway. The variant lines also exhibited a
      specific reduction in the level of DNA synthesis induced by the acute expression
      of the BPV E5 gene, and a variant cell line containing a reduced level of PDGF
      beta receptor also displayed reduced stable growth transformation by the BPV E5
      and v-sis oncogenes. These results provide genetic support for the model that the
      PDGF beta receptor signaling pathway is required for efficient growth
      transformation of C127 cells by the BPV E5 gene.

PMID- 7731696
TI  - Detection of K-ras mutations in DNAs isolated from feces of patients with
      colorectal tumors by mutant-allele-specific amplification (MASA).
AB  - K-ras mutations are found in approximately half of all colorectal tumors
      examined. To explore the possibility of detecting mutated K-ras rapidly and
      efficiently in DNAs isolated from fecal material, we applied the mutant allele
      specific amplification (MASA)-PCR method to DNA from feces of patients with
      colorectal tumors. Among 55 colorectal adenocarcinomas or adenomas examined, 19
      were found to carry K-ras mutations in codons 12 or 13. We were able to PCR
      amplify DNAs isolated from feces of 15 of these 19 patients, but in only three of
      the fecal samples, we were able to detect the K-ras mutations corresponding to
      tumor DNA by MASA and ethidiumbromide staining of the gel. The carcinomas in
      these three cases were more than 40 mm x 40 mm in size and located in the sigmoid
      colon or rectum. However, we identified the K-ras mutations in fecal DNAs of
      additional seven patients by MASA when the gels were blotted and probed with a
      radio-labeled oligonucleotide; the tumors in those patients had arisen in the
      distal half of the colon and the smallest of these tumors was only 7 mm x 5 mm.
      No K-ras mutations were detectable in feces of the remaining five cases, whose
      tumors were relatively small and/or located in the proximal region. The results
      suggested that the MASA-PCR system has potential for development as a simple,
      rapid and noninvasive method for diagnosing the presence of colorectal tumors
      that carry mutant K-ras alleles, particularly tumors located in the distal colon.

PMID- 7731697
TI  - Cloning and characterization of MST, a novel (putative) serine/threonine kinase
      with SH3 domain.
AB  - Protein kinases play a key role in cell growth regulation. We have isolated a
      cDNA fragment of the MST gene from the MKN28 gastric cancer cell line cDNA pool
      by degenerate polymerase chain reaction. MST-cDNAs were cloned from the human
      brain cDNA library. Nucleotide sequence analysis indicated that the MST gene
      encodes a novel putative non-receptor type of serine/threonine kinase with Src
      homology 3 (SH3) domain, two leucine zipper domains and proline rich domain. The
      deduced amino acid sequence corresponding to a part of kinase domain and leucine
      zipper domains of MST (amino acid codons 244-461) is almost identical to the
      published partial amino acid sequence of MLK2. MST is the first non-receptor type
      of serine/threonine kinase containing SH3 domain, leucine zipper domain and
      proline rich domain other than PTK1/Sprk. The MST gene was moderately expressed
      in brain, skeletal muscle and testis as a 3.8 kb mRNA, and the MST gene has been
      mapped to human chromosome 19q13.1-q13.2.

PMID- 7731698
TI  - Mutations in an Alu repeated sequence associated with the DXS43 locus in human
      small cell lung cancers.
AB  - Point mutations in an Alu repeated sequence associated with the DXS43 locus were
      identified in two out of 10 human small cell lung cancers. Since these
      aberrations were identified in DNA from both metastatic lesions and primary
      lesions from the same patient, they would appear to have occurred at a relatively
      early stage. Although this sequence is not apparently associated with known
      genes, these tumor-specific mutations occurred at an early stage may play an
      important role in tumorigenesis.

PMID- 7731699
TI  - Altered subcellular location of an activated and tumour-associated epidermal
      growth factor receptor.
AB  - The epidermal growth factor (EGF) receptor is a membrane bound tyrosine kinase
      whose activity is initiated by ligand binding. The malignant brain tumour
      glioblastoma frequently shows amplification and rearrangements of the EGF
      receptor gene that are associated with the synthesis of a constitutively
      activated tyrosine kinase, lacking amino acids 6-273 near the protein's N
      terminus. When expressed in Chinese hamster ovary (CHO) cells, this mutant
      receptor (p140EGFR) displays ligand-independent tyrosine kinase activity,
      stimulates DNA synthesis, and promotes cell proliferation. Here, we investigate
      the subcellular location of p140EGFR in CHO cell transfectants as well as in
      human glioblastoma tumours. p140EGFR had an intracellular location that
      contrasted sharply with the plasma membrane location of the wild-type EGF
      receptor. Endoglycosidase H sensitivity analysis and the pattern of p140EGFR
      immunoreactivity suggested that the aberrant tyrosine kinase resided primarily in
      the endoplasmic reticulum. The half-life of p140EGFR in the endoplasmic reticulum
      was extended several-fold over that of the ligand-activated wild-type receptor.
      The altered subcellular location of p140EGFR in combination with its prolonged
      half-life suggest that this activated tyrosine kinase may escape the regulatory
      mechanisms utilized for the attenuation of wild-type receptor signaling.
      Therefore, the previously reported growth stimulatory property of the ligand
      independent p140EGFR may be attributed to a sustained tyrosine kinase activity
      resulting from an altered subcellular location.

PMID- 7731700
TI  - Ets-related protein E1A-F can activate three different matrix metalloproteinase
      gene promoters.
AB  - An Ets-related E1A-F has been characterized as an enhancer-binding protein for
      the adenovirus E1A gene. Here we show, in transient expression assays, that E1A-F
      can activate three different subclasses of the matrix metalloproteinase gene
      promoters. Expressions of the chloramphenicol acetyltransferase (CAT) reporter
      gene under the control of stromelysin, type I collagenase and 92 kD type IV
      collagenase promoters were increased approximately 10- to 20-fold by co
      transfection with the E1A-F expression vector. Activation levels were as much
      high as those obtained by exogenous expression of AP-1 transcription factor.
      These results suggest that E1A-F positively regulates transcriptions from matrix
      metalloproteinase genes that are associated with invasion and metastasis of tumor
      cells.

PMID- 7731701
TI  - Cellular proteins binding to the first Src homology 3 (SH3) domain of the proto
      oncogene product c-Crk indicate Crk-specific signaling pathways.
AB  - The widely expressed c-Crk protein, composed of one SH2 and two SH3 domains,
      lacks an apparent catalytic domain, suggesting that it functions through the
      formation of specific complexes with other proteins. Bacterially expressed c-Crk
      formed in vitro highly stable complexes via the first SH3 domain [SH3(N)]. Most
      prominent were a 185 kDa protein of unknown identity (p185), Sos- immunoreactive
      bands of 170 kDa (p170) and 145 to 155 kDa bands, corresponding to the recently
      cloned C3G protein. p170 also bound to Ash/Grb2 and Nck while p185 and C3G bound
      only to Crk. Additional Crk binding proteins were found in hematopoietic cells,
      particularly the myeloid-monocytic lineage. The protein binding properties of Crk
      were subsequently compared to CRKL, the product of a homologous but distinct
      gene, and found to be very similar. The binding of two guanine nucleotide
      exchange factors, Sos and C3G, to Crk and CRKL indicates that Ras or related
      proteins likely play a role in signaling through Crk family proteins.

PMID- 7731702
TI  - Mutational analysis of the carboxy-terminal portion of p53 using both yeast and
      mammalian cell assays in vivo.
AB  - Increasing evidence indicates that p53 is a transcriptional trans-activator
      through its sequence-specific DNA binding domain. Tumor-derived p53 mutations
      disrupt the trans-activation ability mainly due to loss of its sequence-specific
      DNA binding. Using both yeast and mammalian cell assays, the effect of p53
      mutations in the carboxy terminal portion was investigated in order to address
      how p53 mutations outside of the DNA binding domain affect p53 function. The p53
      cDNA in the carboxy-terminus was randomly mutagenized by error-prone polymerase
      chain reactions and the amplified cDNA was screened for the ability to trans
      activate using a yeast assay. Four p53 mutations, including two missense and two
      nonsense mutations located in the carboxy-terminal oligomerization domain, were
      further analysed for trans-activation, cell cycle arrest and colony formation in
      a human osteosarcoma cell line, Saos-2. These functional properties of p53 were
      disrupted by the missense mutations. Surprisingly, one of the nonsense mutations
      disrupts the trans-activation function and the ability to G1 arrest but shows a
      strong inhibition of colony formation. These results confirm that mutations in
      the oligomerization domain can inactivate p53 function and also indicate that p53
      mediated cell growth inhibition does not necessarily depend on the ability to
      arrest cell cycle.

PMID- 7731703
TI  - Complete and tissue-independent methylation of CpG sites in the p53 gene:
      implications for mutations in human cancers.
AB  - CpG dinucleotides are the target of about one third of transition mutations found
      in human genetic diseases and tumors. Methylation at these sites is thought to be
      the cause of these genetic changes through spontaneous deamination of 5
      methylcytosine. In order to define the contribution of 5-methylcytosine to the
      spectrum of p53 mutations in human cancers, we have determined the complete DNA
      methylation pattern along exons 5-8 of the human p53 gene by ligation-mediated
      polymerase chain reaction genomic sequencing. The study was conducted with nine
      different types of normal human tissue and cell lines, including skin
      fibroblasts, keratinocytes, lung epithelial cells, mammary epithelial cells and
      colonic mucosa cells. We found that the p53 sequences along exons 5-8 are
      completely methylated at every CpG site, including 46 different sites on both DNA
      strands. This methylation pattern is tissue-independent suggesting that tissue
      specific methylation does not contribute to the differential mutation patterns
      seen in tumors. The occurrence of mutational hotspots at specific CpG sites is
      not related to selective methylation of only a subset of CpGs but may rather
      depend on a selection bias for particular amino acid changes. Our results are not
      inconsistent with theories that mutations in tumors with high CpG mutation rates,
      like colon cancer, are caused by spontaneous deamination of 5-methylcytosine and
      mutations in tumors with a lack of CpG involvement reflect superimposed
      fingerprints from exogenous carcinogens. However, given the lack of tissue
      specificity of methylation, alternative explanations (eg targeting of methylated
      CpG sites by tissue-selective carcinogens) should be considered to explain the
      high percentage of CpG mutations in some tumor types.

PMID- 7731704
TI  - Overexpression of human cyclin A advances entry into S phase.
AB  - Cyclin A is a cell cycle regulatory protein that functions in mitotic and S-phase
      control in mammalian cells. Using a genomic construction corresponding to the
      human cyclin A gene under the control of its own promoter, we have established
      stable transfectants overexpressing cyclin A protein. Experiments assisted by
      laser scanning image cytometry showed that this overexpression begins from late
      G1 phase onwards and is therefore cell cycle-regulated in this model. We
      demonstrated that this overexpression advances entry into S phase, leading to a
      contraction of the overall cell generation time. These results provide evidence
      that cyclin A can be a rate-limiting factor with respect to the control of the
      transition to S phase in mammalian cells.

PMID- 7731705
TI  - Translocation (12;22) (p13;q11) in myeloproliferative disorders results in fusion
      of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11.
AB  - In myeloid and lymphoid leukemias recurrent chromosomal aberrations can be
      detected in chromosome region 12p13. We characterized the genes involved in
      t(12;22) (p13;q11) in two patients with myeloid leukemia and one with
      myelodysplastic syndrome (MDS). MN1, a gene on chromosome 22q11 was shown to be
      fused to TEL, a member of the family of ETS transcription factors on chromosome
      12p13. The translocation results in transcription of the reciprocal fusion mRNAs,
      MN1-TEL and TEL-MN1, of which MN1-TEL is likely to encode an aberrant
      transcription factor containing the ETS DNA-binding domain of TEL. In addition to
      fusion of TEL to the PDGF beta receptor in t(5;12) in chronic myelomonocytic
      leukemia (CMML), our data suggest that the involvement of this protein in myeloid
      leukemogenesis could be dual; its isolated protein-protein dimerization and DNA
      binding domains may be crucial for the oncogenic activation of functionally
      different fusion proteins.

PMID- 7731706
TI  - Cloning and characterization of MN1, a gene from chromosome 22q11, which is
      disrupted by a balanced translocation in a meningioma.
AB  - We have isolated a gene, called MN1, which resides on chromosome 22 and which was
      found to be disrupted by a balanced translocation (4;22) in meningioma 32. The
      MN1 gene spans about 70 kb and consists of at least two large exons of
      approximately 4.7 kb and 2.8 kb. The MN1 cDNA codes for a protein of 1319 amino
      acids when the first methionine in the open reading frame is used. The MN1 cDNA
      contains two CAG repeats, one of which codes for a string of 28 glutamines. The
      t(4;22) disrupts the 5'-exon within the open reading frame. In meningioma 32 no
      expression of the MN1 mRNA is observed. These results suggest that inactivation
      of the MN1 gene in this tumour may contribute to its pathogenesis.

PMID- 7731707
TI  - Proto-oncogenic properties of the DP family of proteins.
AB  - The cellular transcription factor DRTF1/E2F is implicated in the control of
      cellular proliferation due to its interaction with key regulators of cell cycle
      progression, such as the retinoblastoma tumour suppressor gene product, cyclins
      and cyclin-dependent kinases. DRTF1/E2F is a heterodimeric DNA binding activity
      which arises when a member of two distinct families of proteins, DP and E2F,
      interact as DP/E2F heterodimers, for example, DP-1 and E2F-1. In DRTF1/E2F the
      activity of DP-1 is under cell cycle control, possibly by phosphorylation, and in
      many types of cells it is a frequent, if not general DNA binding component of
      DRTF1/E2F. The expression of other DP proteins, such as DP-2, is tissue
      restricted. Here, we show that DP-1 and DP-2 are integrated with another growth
      regulating pathway which involves signal transduction emanating from activated
      Ras protein. Thus, activated Ha-ras can co-operate with DP-1 or DP-2 in the
      transformation of rat embryo fibroblasts, establishing for the first time that DP
      proteins are endowed with proto-oncogenic activity. Moreover, an analysis of a
      dominant-negative and mutant DP-1 proteins suggests that the primary target
      through which DP-1 mediates its oncogenic activity is unlikely to be due to the
      regulation of E2F site-transcription, suggesting an E2F-independent effector
      function for DP-1. These results therefore establish DP genes as proto-oncogenes
      and thus argue that deregulating the normal control of DP protein activity will
      be important in promoting aberrant cellular proliferation.

PMID- 7731708
TI  - Overexpression of the retinoic acid receptor gamma directly induces terminal
      differentiation of human embryonal carcinoma cells.
AB  - All-trans retinoic acid (RA) exerts profound effects on the growth and
      differentiation of normal, embryonic, and malignant cells. The effects of RA are
      mediated through multiple members of the retinoic acid receptor (RAR) and
      retinoid X receptor (RXR) families of nuclear transcription factors. The RARs and
      RXRs exhibit specific patterns of expression during development and in adult
      tissues suggesting tissue or cell-type specific functions. Using NTera2/clone D1
      (NT2/D1) human embryonal carcinoma cells as a model, we report that the RA
      induced terminal differentiation of these cells into a neuronal phenotype is
      characterized by an increase in expression of RAR alpha, RAR beta, RAR gamma, and
      a slight induction of RXR alpha. To study the role of these receptors in the
      differentiation process we individually overexpressed RAR alpha, beta, gamma and
      RXR alpha in NT2/D1 cells by cDNA transfection. Using induced cDNA expression by
      episomal vector amplification we show that RAR gamma over-expression causes the
      terminal mesenchymal differentiation of these cells while over-expression of RAR
      alpha, beta and RXR alpha has no observed maturation or growth inhibitory
      effects. Over-expression of these receptors in the derived RA resistant subclone
      NT2/D1-R1 showed phenotypic changes characteristic of RA response in RAR gamma
      transfectants. These studies indicate that of the retinoid receptors expressed in
      RA-treated NT2/D1 cells, it is the upregulation of RAR gamma that specifically
      induces the terminal differentiation of these cells.

PMID- 7731709
TI  - Alterations in the structure of the EBV nuclear antigen, EBNA1, in epithelial
      cell tumours.
AB  - The EBV nuclear antigen, EBNA1, is the only viral protein consistently expressed
      in all virus-infected cells. It is required in trans for viral replication,
      maintenance of EBV extrachromosomal episomes, and transcriptional transactivation
      in latently-infected B-cells. It binds RNA suggestive of a regulatory role in
      post-transcriptional events and in transgenic mice, it is tumorigenic. In RNase
      protection studies relating to the EBV-associated tumour, nasopharyngeal
      carcinoma (NPC), we show that a C-terminal EBNA1 RNA probe from the prototype B95
      8 marmoset strain can protect its own mRNA from enzymatic digestion, but does not
      fully protect EBNA1 mRNA from NPC cells. This finding is consistent with changes
      in the coding region for the antigen. We thus determined the sequences of EBNA1
      genes derived from an NPC xenograft and numerous patient biopsies and identified
      a number of mutations in the gene in these human cells, relative to B95-8. Many
      of the nucleotide changes would lead to non-conservative amino acid alterations
      in apparently functionally significant regions of the protein. We show that
      although some of the mutations lie in regions designated as critical to DNA
      binding, they have negligible effect on this property of EBNA1. The basic regions
      in EBNA1 that may bind to RNA, at least in vitro, are exempt from mutation. Thus,
      unless the alterations are 'silent', which for such a critical viral function
      seems unlikely, they may relate to as yet unmapped viral activities, such as a
      role in tumorigenesis and the ability of EBNA1 to evade the cellular immune
      system, or be associated with the ability of the antigen to regulate gene
      transcription.

PMID- 7731710
TI  - Fibroblast growth factor receptors display both common and distinct signaling
      pathways.
AB  - We compared the mitogenic and signaling pathways of three Fibroblast Growth
      Factor Receptors (FGFRs), FGFR1, KGFR and FGFR4 in the same cell line. Each
      receptor was expressed in L6E9 rat myoblasts that do not normally express
      detectable levels of FGFRs and clones that express comparable levels of each
      receptor were selected. Our results show that FGFs induce an effective survival
      and growth of FGFR1 and KGFR expressing cells. In addition, these cells exhibit a
      morphology that is reminiscent of that of malignantly transformed cells and
      display anchorage independent growth in a ligand dependent manner. Unlike KGFR
      and FGFR1, FGFR4 mediates a less effective growth, and cells overexpressing this
      receptor do not undergo any morphological changes nor do they display an
      anchorage independent growth in response to FGFs. All three receptors exhibit
      both quantitative and qualitative differences in their ability to induce tyrosine
      phosphorylation of cellular substrates. Both FGFR1 and KGFR induce strong
      phosphorylation of phospholipase C-gamma and a 90 kDa protein, while FGFR4
      induces a relatively weak phosphorylation of phospholipase C-gamma and completely
      fails to induce phosphorylation of the 90 kDa. The three receptors also induce
      phosphorylation of the mitogen activated protein kinases (MAPK) but the effect of
      FGFR1 is far stronger than that of the other two receptors. Since FGFR4 is
      expressed in myoblasts in vivo, we examined whether this receptor can function in
      the differentiation pathway of myoblasts. Contrary to its weak mitogenic
      activity, FGFR4 effectively mediates the inhibition of myogenic differentiation
      in L6E9 cells and also suppresses the expression of the myogenic regulatory
      protein myogenin. Taken together, our results suggest that the signaling
      mechanism of FGFR4 differs from that of FGFR1 and KGFR, and that the primary role
      of FGFR4 in myoblasts may be the maintenance of their non differentiated state.

PMID- 7731711
TI  - p53-mediated apoptosis in HeLa cells can be overcome by excess pRB.
AB  - Studies on DNA tumor viruses have suggested a link between p53 and pRB in the
      control of cell growth and apoptosis. We examined the role of pRB in the control
      of p53-mediated apoptosis in HeLa cells, in which the activities of p53 and
      members of the pRB family are very low. Transient overexpression of wild type
      (wt) p53 in HeLa cells induced apoptotic cell death. Importantly, coexpression of
      functional pRB resulted in significant protection of HeLa cells from p53-mediated
      apoptosis, without interfering with the transcriptional activity of wt p53. These
      results suggest that pRB, and possibly other pRB-related proteins, play a major
      role in the decision of whether cells respond to activated p53 by undergoing
      growth arrest or apoptosis. Our findings demonstrate a direct link between these
      two tumor suppressors in the control of cell growth and cell death.

PMID- 7731712
TI  - Identification of full-length and truncated forms of Ehk-3, a novel member of the
      Eph receptor tyrosine kinase family.
AB  - Factors that bind and activate receptor tyrosine kinases are known to play key
      roles during development and in the adult. The Eph-related receptors constitute
      the largest known family of receptor tyrosine kinases. Members of the Eph family
      exhibit intriguing patterns of expression in the embryo, implicating them in a
      variety of developmental processes, and their expression is often restricted to
      particular subpopulations of postmitotic neurons in the adult. We describe the
      identification and characterization of a novel member of the Eph receptor family,
      which we have termed Ehk-3 for Eph Homologous Kinase 3. Ehk-3 displays all the
      major structural features shared by other members of the Eph family, including a
      cysteine-rich region and tandem fibronectin type-III domains in its extracellular
      portion. Ehk-3 is expressed in two forms in a developmentally-regulated fashion:
      a conventional full-length version containing the intracellular tyrosine kinase
      domain, as well as a truncated form that lacks this domain. Both forms of Ehk-3
      are quite restricted to the nervous system in the adult, but Ehk-3 is more widely
      expressed in the embryo, suggesting that Ehk-3 mediates different functions
      during development and in the adult.

PMID- 7731713
TI  - The DCC gene suppresses the malignant phenotype of transformed human epithelial
      cells.
AB  - Loss of heterozygosity and loss of expression of the deleted in colon cancer
      (DCC) gene is frequently observed in a number of different cancer types. To
      determine if the DCC gene plays a direct role in tumor suppression, wild-type
      full-length or truncated DCC cDNA constructs were transfected into
      nitrosomethylurea (NMU) transformed tumorigenic HPV-immortalized human epithelial
      cells that had allelic loss and reduced expression of DCC. Full-length DCC
      suppressed tumorigenicity whereas truncated DCC did not. Tumorigenic reversion of
      initially suppressed transfectants was associated with loss of DCC expression and
      loss or rearrangement of transfected DCC sequences. These results provide the
      first direct evidence that DCC is a tumor suppressor gene.

PMID- 7731714
TI  - Interaction of metastasis associated Mts1 protein with nonmuscle myosin.
AB  - The mts1 gene codes for a 101 amino acid protein which belongs to the subfamily
      of S100 Ca(2+)-binding proteins and is overexpressed in metastatic cancers as
      compared to their nonmetastatic counterparts. While the Mts1 protein is
      putatively involved in cytoskeletal-membrane interactions, its exact
      physiological role is not known. In order to gain insight into the biological
      function of Mts1, its expression was monitored throughout mouse embryogenesis as
      well as in normal adult mouse tissues. In situ hybridizations of mouse embryos
      showed expression of mts1 mRNA to be highest in trophoblast cells of a day 8 old
      embryo. In normal adult mouse tissues, immunocytochemistry revealed Mts1
      expression in a T-cell specific pattern in both the thymus and spleen. These
      results indicate that the expression of mts1 is prevalent in motile cell types,
      and to further elucidate the role of Mts1, gel overlay and GST-fusion protein
      experiments were performed to identify proteins that interact with the Mts1
      protein. Nonmuscle myosin II was found to interact with Mts1, suggesting a role
      for Mts1 in the process of motility and lending credence to the hypothesis that
      Mts1 may enhance metastatic potential by increasing the motility of cancerous
      cells.

PMID- 7731715
TI  - Deregulation of c-abl mediated cell growth after retroviral transfer and
      expression of antisense sequences.
AB  - To determine the role of c-abl during cell growth, we constructed a retrovirus
      vector alpha A, capable of expressing an antisense RNA directed against the abl
      mRNA. Based on v-abl-mediated 3T3 transformation assay, we showed that the number
      of transformed foci was reduced 50-94% when alpha A-infected 3T3 cells were
      superinfected with A-MuLV. Up to a 100% of inhibition could be observed when the
      time of infection was lengthened. Introduction of the antisense sequence into
      NIH3T3 cells resulted in reduction of growth rate. These cells entered into S
      phase from G1 phase of the cell cycle earlier in time than untransduced cells.
      Thus c-abl serves as a checkpoint during G1/S transition in the cell cycle, and
      its reduction resulted in deregulation of cell growth.

PMID- 7731716
TI  - Effects of heterozygosity for the Rb-1t19neo allele in the mouse.
AB  - We describe the pathology of a cohort of 80 mice heterozygous for an inactive
      allele of the Rb-1 tumour suppressor gene. The majority of these mice developed
      locally invasive tumours, arising from the pituitary gland. The time of onset of
      overt signs of disease in mice known to have inherited their mutant allele
      paternally shows a small but statistically significant shift to the lower end of
      the spectrum, suggesting that tumorigenesis is influenced by gametic imprinting.
      In situ hybridisation analysis demonstrates the presence in the tumours of pro
      opiomelanocortin mRNA, which is normally found both in corticotroph and
      melanotroph cells. Mice within this cohort also develop systemic defects. Most
      notably, there is increased siderosis in the spleen indicating the possibility of
      an abnormality in red blood cell turnover. This is consistent with the
      abnormalities of erythropoiesis described previously in homozygous Rb-1-deficient
      mice. In addition, a proportion of mice developed liver steatosis, probably
      representing the end organ effects of hormonal imbalance as a direct consequence
      of tumour presence. A significant proportion showed C cell hyperplasia in the
      thyroid. The spectrum of pathology in mice differs from that in the human but
      does provide a useful model of site-specific tumour predisposition.

PMID- 7731717
TI  - The cloning of Grb10 reveals a new family of SH2 domain proteins.
AB  - SH2 domains function to bind proteins containing phosphotyrosine and are
      components of proteins that are important signal transducers for tyrosine
      kinases. We have cloned SH2 domain proteins by screening bacterial expression
      libraries with the tyrosine phosphorylated carboxyterminus of the epidermal
      growth factor (EGF) receptor. Here we report the identification of a new SH2
      domain protein, Grb10. Grb10 is highly related to Grb7, an SH2 domain protein
      that we have previously identified. In addition to an SH2 domain, Grb7 and Grb10
      have a central domain with similarity to a putative C. elegans gene likely to be
      involved in neuronal migration. At least three forms of Grb10 exist in
      fibroblasts apparently due to alternate translational start sites. Grb10
      undergoes serine but not tyrosine phosphorylation after EGF treatment resulting
      in a shift mobility in a large fraction of Grb10 molecules. However Grb10 appears
      to bind poorly to EGF-Receptor and the true binding partner for the Grb10 SH2
      domain is unclear. Grb10 maps to mouse chromosome 11 very close to the EGF
      Receptor which is remarkably similar to Grb7 that maps near the EGF-Receptor
      related HER2 receptor. The finding of multiple family members with evolutionarily
      conserved domains indicates that these SH2 domain proteins are likely to have an
      important, although as of yet, unidentified function.

PMID- 7731718
TI  - The motogenic and mitogenic responses to HGF are amplified by the Shc adaptor
      protein.
AB  - The receptor of Hepatocyte Growth Factor-Scatter Factor (HGF) is a tyrosine
      kinase which regulates cell motility and growth. After ligand-induced tyrosine
      phosphorylation, the HGF receptor associates with the Shc adaptor, via the SH2
      domain. Site-directed mutagenesis of the HGF receptor indicates that
      phosphotyrosines Y1349VHV and Y1356VNV can work as docking sites for Shc. The Kd
      of this interaction, measured in real time using synthetic phosphopeptides and
      recombinant Shc on a BIAcore biosensor, is 150 nm for both sites. After
      stimulation of the HGF receptor, Shc is phosphorylated on Y317VNV, generating an
      high affinity binding site for Grb2 (Kd = 15 nM). This duplicates the high
      affinity binding site for Grb2 present on the HGF receptor (Y1356VNV). Thus HGF
      stimulation can trigger the Ras pathway by recruiting Grb2 both directly through
      the receptor, and indirectly, through Shc. Overexpression of wild-type Shc, but
      not of the Y317-->F mutant, enhances cell migration and growth in response to
      HGF. These data show that Shc is a relevant substrate of the HGF receptor, and
      works as an 'amplifier' of the motogenic as well as of the mitogenic response.

PMID- 7731719
TI  - DNA repair in the endogenous and episomal amplified c-myc oncogene loci in human
      tumor cells.
AB  - We have studied the repair of u.v.-induced cyclobutane pyrimidine dimers (CPDs)
      in amplified c-myc oncogene loci in human colon cancer cells to better understand
      the relationship between chromatin structure, transcription and DNA repair. To
      assess the variation in DNA repair in the same gene whether located in a
      chromosomal site or in a extra-chromosomal site, we have quantitated the
      efficiency of excision repair after u.v. exposure in the endogenous and episomal
      c-myc genes isolated from COLO320HSR and DM cells. In the HSR cells, c-myc is
      localized in a homogeneously staining region (HSR), and in the DM cells, the gene
      is localized in double minute chromosomes (DM). Our results indicate that the
      repair is less efficient in c-myc amplicons organized as double minute
      chromosomes than in the endogenous c-myc amplicons. The episomal gene is not
      repaired with the same efficiency as when it is intrachromosomal. This may
      reflect differences in chromatin structure. An advantage of this biological
      system is that the cells possess two different alleles of the c-myc gene, one
      that is active and another which is inactive. We have studied the relationship
      between DNA repair and transcriptional activity in the c-myc locus by measuring
      the efficiency of excision repair after u.v. exposure in the normal and
      rearranged alleles of the c-myc gene. Surprisingly, the c-myc gene is repaired
      with similar efficiency in the highly transcribed allele as in the poorly
      expressed allele. However, u.v. damage is selectively removed from the
      transcribed strand of the active c-myc allele, but DNA repair is not strand
      specific in the non-expressed c-myc allele.

PMID- 7731720
TI  - B-Raf protein isoforms interact with and phosphorylate Mek-1 on serine residues
      218 and 222.
AB  - The B-raf/c-Rmil proto-oncogene belongs to the raf/mil family of serine/threonine
      protein kinases. It encodes multiple protein isoforms resulting from alternative
      splicing of two exons located upstream of the kinase domain. Recent studies
      suggested that B-Raf could be the intermediate molecule between Ras and Mek-1
      (MAP Kinase Kinase) in signalling pathways specific of neural cells. However,
      there has been no evidence for a direct interaction between B-Raf and Mek-1. We
      report here that different B-Raf isoforms can be co-immunoprecipitated with anti
      Mek-1 antisera in COS-1 cells and that the kinase activity of B-Raf is not
      required for its interaction with Mek-1. We also show that all B-Raf isoforms
      tested phosphorylate Mek-1 in a time-dependent manner, whereas kinase defective
      mutants fail to do so. Finally, we demonstrate that the constitutively activated
      S218D, S222D and S218D/S222D mutants of Mek-1 interact similarly with B-Raf.
      However, only the S218D and S222D mutants, and not the S218D/S222D double mutant,
      can be phosphorylated by B-Raf isoforms. Therefore, serine residues 218 and 222,
      previously shown to regulate Mek-1 activity, appear to be the major
      phosphorylation sites by B-Raf in vitro.

PMID- 7731721
TI  - Frequent alterations of chromosome 1 in ductal carcinoma in situ of the breast.
AB  - Ductal carcinoma in situ (DCIS) of the breast is commonly described as a
      premalignant lesion. Using PCR to amplify DNA from areas of tumour cells which
      have been microdissected from fixed material, we have studied the involvement of
      chromosome 1 in 19 cases of DCIS. A series of microsatellite repeat polymorphisms
      has been used to define regions of allelic imbalance and this has confirmed the
      involvement in DCIS of six of the regions previously implicated in studies of
      invasive breast tumours. This suggests that these regions may harbour tumour
      suppressor genes, the inactivation of which is important for the early stages of
      breast tumour development. Analysis of separate ducts from within the same tumour
      has revealed that the same genetic alterations are not necessarily present
      throughout the lesion. In addition we have found that in three cases where frank
      invasive carcinoma is also present, similar alterations can be detected in the in
      situ and invasive component.

PMID- 7731722
TI  - Differential regulation of Max and role of c-Myc during erythroid and
      myelomonocytic differentiation of K562 cells.
AB  - The protein Max binds to c-Myc and the heterodimer c-Myc/Max seems to be the
      active form in vivo. While the expression of c-myc is extensively regulated, no
      major changes in max expression have been reported so far with respect to
      differentiation. We have studied the expression of c-Myc and Max during in vitro
      differentiation of the bipotent human myeloid leukemia K562 cell line. This cell
      model system allowed us to compare c-Myc and Max expression during
      differentiation along erythroid (induced by 1-beta-D-arabinofuranosyl-cytosine)
      and myelomonocytic lineages (induced by 12-0-tetradecanoylphorbol-13-acetate). We
      found that c-myc expression decreased as a result of both differentiating
      treatments. The expression level of max remained unchanged during myelomonocytic
      differentiation. In contrast, max mRNA and protein were dramatically down
      regulated during erythroid differentiation of K562 cells, thus demonstrating that
      max gene is subjected to regulation during differentiation. We also studied the
      expression of the other two described members of the c-Myc network: mxi1 and mad.
      mxi1 expression increased during erythroid differentiation but was strongly down
      regulated during myelomonocytic differentiation of K562. mad was constitutively
      expressed during K562 erythroid differentiation and slightly increased during
      induction of the myelomonocytic pathway. We have obtained K562 sublines stably
      transfected with a zinc-inducible c-myc gene. In these clones the overexpression
      of c-Myc did not interfere with TPA-induced myelomonocytic differentiation. In
      contrast, erythroid differentiation was significantly inhibited upon c-myc
      induction despite the down-regulation of endogenous max expression. These results
      suggest a differential role for c-Myc in the human myeloid cell differentiation
      depending on the cell lineage.

PMID- 7731723
TI  - Molecular cloning and functional characterization of the human platelet-derived
      growth factor alpha receptor gene promoter.
AB  - Expression of the platelet-derived growth factor alpha receptor (PDGF alpha R) is
      strictly regulated during mammalian development and tumorigenesis. The molecular
      mechanisms involved in the specific regulation of PDGF alpha R expression are
      unknown, but transcriptional regulation of the PDGF alpha R gene is most likely
      to be involved. This study describes the molecular cloning of the non-coding exon
      1 and approximately 2 kb of 5' flanking region of the human PDGF alpha R gene.
      This 5' flanking region is a functional promoter of the PDGF alpha R gene as
      concluded from its capacity to drive luciferase reporter gene expression in an
      orientation dependent way. Analysis of 5' promoter deletion mutants revealed that
      the region from -441 to +118, relative to the transcription initiation site, is
      sufficient to establish high level promoter activity. In addition, the morphogen
      retinoic acid, alone or in combination with dibutyryl cAMP, gives a 22-fold
      induction of PDGF alpha R gene promoter activity in human teratocarcinoma cells.
      This effect is mediated through specific transcription factor binding within the 
      52/+118 region of the PDGF alpha R gene.

PMID- 7731724
TI  - Consistent loss of the wild type allele in breast cancers from a family linked to
      the BRCA2 gene on chromosome 13q12-13.
AB  - A small proportion of breast cancer is attributable to the inheritance of
      dominant, high penetrance susceptibility genes. One of these genes, BRCA2, has
      recently been localised by genetic linkage analysis to chromosome 13q12-13. This
      is a region known to exhibit loss of heterozygosity in 20-40% sporadic breast
      cancers. In this study, we have examined cancers from a family showing strong
      evidence of linkage to BRCA2. LOH was seen in seven out of eight informative
      cancers. In all cases the allele lost was the wild type allele that does not
      segregate with the disease in the family. The data suggest that both alleles of
      BRCA2 are inactivated in cancers, the pattern expected of a recessive oncogene or
      tumour suppressor gene.

PMID- 7731725
TI  - Exclusion of the Wilms tumour gene (WT1) promoter as a site of frequent mutation
      in Wilms tumour.
AB  - WT1 is a tumour suppressor gene expressed in a specific temporal and spatial
      pattern in the developing kidney. Up to 15% of Wilms tumours have point mutations
      in the WT1 gene coding sequence. We have now investigated whether mutations in
      the WT1 promoter could be associated with loss of control WT1 expression and
      subsequent Wilms tumour formation. Using single-strand conformational
      polymorphism (SSCP) analysis we analysed 39 sporadic Wilms tumours for WT1
      promoter mutations. We found six linked common sequence polymorphisms and two
      unlinked less frequent polymorphisms which allowed us to identify four tumours
      with loss of heterozygosity but none with point mutations, small deletions,
      insertions or rearrangements. We therefore conclude that WT1 promoter mutations
      are unlikely to play an important role in Wilms tumorigenesis.

PMID- 7731726
TI  - Characterization of MEK1 phosphorylation by the v-Mos protein.
AB  - Activation of MAP kinase/Erk Kinase (MEK) via direct phosphorylation by Mos may
      be crucial for cellular transformation by the activated c-mos or v-mos gene.
      Recent studies on a number of different protein kinases showed that
      phosphorylation within a subdomain of the catalytic domain may represent a common
      mode of activation. In this regard, activation of MEK1 by Raf involves
      phosphorylation of serine residues 218 and 222. Here we show that recombinant
      kinase-inactive MEK1 is phosphorylated by v-Mos with equal efficiency at both Ser
      218 and Ser 222 in vitro. Tryptic phosphopeptide analysis of glutathione-S
      transferase (GST)-MEK1 K97R and its alanine-for-serine mutants indicated that Ser
      222 is the preferred phosphorylation site. Wild-type GST-MEK1 was phosphorylated
      at the same sites but contained a significantly lower amount of doubly
      phosphorylated species then its K97R kinase-inactive mutant. The ratio of GST
      MEK1 species phosphorylated at two serines to those phosphorylated at one serine
      was similar in auto-phosphorylated and v-Mos-phosphorylated GST-MEK1. Consistent
      with the in vitro data, phosphopeptide mapping of MEK1 immunoprecipitated from
      mos transformed cells showed an increased amount of singly phosphorylated
      phosphopeptide compared to nontransformed cels. MEK1 was found to be more highly
      activated in NIH3T3 cells transformed by an activated c-mos or v-mos gene than in
      cells growing normally in medium containing serum. Our data indicate that Mos
      activated MEK1 in vitro as well as in vivo by phosphorylating Ser 222.

PMID- 7731727
TI  - Create oncology education opportunities for generalist nurses.

PMID- 7731728
TI  - Are you committing strategic resume errors that can sabotage your job-search
      campaign?

PMID- 7731729
TI  - Issue: mandatory continuing education for relicensure.

PMID- 7731730
TI  - Relationships between maternal malaria and malarial immune responses in mothers
      and neonates.
AB  - Immune responses of 97 Gambian women and their neonates were studied. New methods
      distinguished between active and previous placental malaria, were used to examine
      relationships between maternal malaria and neonatal immune responses. Many
      placentas (61%) had active or previous malarial infection. Maternal and cord
      malarial IgG levels correlated (P < 0.001). Malarial IgG was raised in cord blood
      in active placental malaria; IgM was not detected. Mean lymphoproliferation and
      the proportion of responders to soluble P. falciparum antigens (F32) and
      conserved regions of p190 expressed on trophozoites and schizonts (190L and 190N)
      were higher in neonates than mothers. There was no clear relationship between
      maternal malaria and neonatal mean lymphoproliferation to malarial antigens,
      although fewer neonates responded when mothers were actively infected. Matched
      maternal and neonatal lymphoproliferation responses did not correlate. However,
      first born neonatal lymphoproliferation to PPD and malarial antigens appeared
      lower than other neonates, in agreement with lower lymphoproliferation in
      primigravidae compared with multigravidae. Also in common with mothers,
      autologous plasma suppressed neonatal lymphoproliferation to PPD and malarial
      antigens, suggesting common immunoregulation. Higher cortisol or other
      circulating factors in first pregnancies may be implicated. The relevance of cell
      mediated malarial immune responses detected at birth remains to be established.

PMID- 7731731
TI  - Human immune recognition of recombinant proteins representing discrete domains of
      the Plasmodium falciparum gamete surface protein, Pfs230.
AB  - The 230 kD gametocyte/gamete-specific surface protein of Plasmodium falciparum,
      Pfs230, is a target of antibodies which inhibit the development of the parasite
      inside the mosquito vector. A transmission blocking vaccine based on Pfs230 may
      be a powerful tool for malaria control. As a first step, Pfs230 has been
      expressed in E. coli as a series of recombinant proteins, fused to maltose
      binding protein. We have used the fusion proteins to assess cellular and humoral
      immune responses to Pfs230 in malaria-immune adult Gambian blood donors;
      responses to the fusion proteins have been compared with responses to native
      Pfs230. The tetrapeptide repeat region of the molecule appears to be
      immunodominant for both antibody-producing cells and peripheral blood T cells. We
      postulate that this may represent a mechanism for immune evasion since the N
      terminal repeat region of the molecule is cleaved from the mature protein and
      shed into the plasma. Responses to fusion proteins representing the seven
      cysteine motifs were correlated within individual donors, suggesting that cross
      reactive epitopes occur within the motifs. Antibody responses to recombinant
      proteins were poorly correlated with responses to native Pfs230 suggesting that
      dominant epitopes of the native protein are not adequately represented in the
      recombinant proteins. Although prokaryotic expression products may be suitable
      for induction of cellular immune responses to Pfs230, alternative expression
      systems may be needed for creation of appropriate B cell epitopes.

PMID- 7731732
TI  - Cytotoxicity in human mucosal and cutaneous leishmaniasis.
AB  - CD8+ T cells and lysis of parasitized macrophages seem to be important in the
      resistance to murine leishmaniasis. In the present study, we evaluated peripheral
      blood mononuclear cell (PBMC) from patients with either cutaneous (CL) or mucosal
      (ML) leishmaniasis in cell lysis assays using 51-Cr-labeled Daudi or K562 cells,
      or autologous antigen-pulsed macrophages as targets. Results are reported as
      lytic units (number of cells required for 30% lysis) per million PBMC. Exposure
      of patient PBMC (n = 12) to lysate from Leishmania amazonensis promastigotes led
      to an increase in cytotoxic activity compared to unstimulated patient cells
      against Daudi (81.8 +/- 14.9 vs 13.6 +/- 5 lytic units (LU) per million PBMC;
      mean +/- SEM) and K562 (65.7 +/- 8.4 vs 13.1 +/- 5 LU/10(6) PBMC). ML had higher
      responses than CL in both targets (80.4 +/- 11.0 vs 46.4 +/- 11.6 LU/10(6) PBMC
      for K562, and 104.3 +/- 23.8 vs 59.3 +/- 14.3 LU/10(6) PBMC for Daudi). Normal
      control PBMC, stimulated with L. amazonensis antigen had 6.32 +/- 3.72 LU/10(6)
      PBMC against Daudi cells and 9.06 +/- 2.78 LU/10(6) PBMC against K562. The cell
      responsible for lysis of the K562 cells was characterized as NK, by means of cell
      separation employing magnetic beads coupled to antibodies. Addition of
      recombinant TGF-beta or recombinant human IL-10 reduced L. amazonensis-induced
      cytotoxicity by 90% and 70%, respectively. Cytotoxicity of antigen-stimulated
      PBMC was also demonstrated against autologous L. amazonensis antigen-pulsed
      macrophages in the range of 6.7 to 41.7 LU/10(6) PBMC.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7731733
TI  - Immunohistochemical localization of excretory/secretory antigens in adult
      Ancylostoma caninum using monoclonal antibodies and infected human sera.
AB  - Human eosinophilic enteritis (EE) may result from hypersensitivity to the
      excretory/secretory (ES) antigens of adult Ancylostoma caninum. The origin of
      several antigens were identified by probing adult A. caninum with mouse
      monoclonal antibodies (MoAbs), sera from mice vaccinated with ES antigens and
      sera from human EE patients. Six MoAbs (AC/ES 1-6) were produced against ES
      antigens, two being IgG3 and four IgM. Western blots demonstrated four different
      antigen specificities: MoAb AC/ES 1 bound strongly to an ES product at about 30
      kDa; AC/ES 2 recognized a broad band ranging from 50-200 kDa; AC/ES 3, AC/ES 5
      and AC/ES 6 reacted at about 68 kDa, and AC/ES 4 at about 97 kDa. Sections of
      formalin-fixed, paraffin embedded adult A. caninum were then incubated with these
      MoAbs and immunostained by the peroxidase-anti-peroxidase (PAP) technique. The
      target epitope of MoAb AC/ES 1 was found mainly in the oesophageal, amphidial and
      excretory glands; AC/ES 2 reacted weakly with many structures in the sections;
      AC/ES 3, AC/ES 5 and AC/ES 6 were specific for excretory glands only, and AC/ES 4
      bound to amphidial glands. Sera from immunized mice reacted with all three
      (especially the excretory) glands and the cuticle. In an indirect assay, worm
      sections probes with three human EE patient sera demonstrated maximal staining in
      the amphidial glands. Our findings confirm that ES products of A. caninum include
      immunogenic glandular secretions which may be involved in the pathogenesis of
      human EE.

PMID- 7731734
TI  - Cellular responses during liver fluke infection in sheep and its evasion by the
      parasite.
AB  - The cellular immune response in sheep to an acute and chronic primary and an
      acute secondary liver fluke infection were examined by immunohistology of liver
      tissue and flowcytometry of lymphocytes from the draining hepatic lymph nodes.
      Ten days after primary infection, portal tract areas surrounding migratory
      tunnels were infiltrated with CD4+ and CD8+ lymphocytes with fewer B cells and
      T19+ T cells. Micro abscesses were distributed sporadically in the liver
      parenchyma and young flukes could be easily observed in the liver tissue free
      from inflammatory cells. More intensive infiltration of the portal tract areas
      was observed during a secondary liver fluke infection characterized by a
      pronounced increase in eosinophils, B cells and CD4+ T cells. In addition, there
      was an increase in MHC class II+ fibroblastic-like cells surrounding the
      migratory tracts. In contrast to the primary infection, no young flukes were
      observed in the same tissue areas during the secondary infection. Chronic primary
      infections were characterized by perilobular fibrosis and a predominance of CD8+
      and gamma delta-TCR+T19- T cells distributed within fibrotic strands. Distinct B
      cell follicles were observed in the fibrotic strands and near major bile ducts
      and necrotic patches. Pronounced lymphocyte infiltration could occasionally be
      observed surrounding liver fluke eggs lodged in liver tissue. A progressive
      increase in lymph node weight, cell number and CD4/CD8 ratio was observed in the
      acute and chronic primary infections. The role of the infiltrating cell
      populations and possible mechanism of immune evasion by the parasite are
      discussed.

PMID- 7731735
TI  - Identification and characterization of excreted/secreted products of Trichuris
      trichiura.
AB  - This study provides the first description of the range and immunogenicity of
      proteins excreted and/or secreted by living T. trichiura adult worms following
      their recovery from the human large intestine. Metabolic labelling of T.
      trichiura excretory/secretory (ES) products with [35S]-methionine revealed a
      range of proteins with prominent components at 52-54 kDa, 35-45 kDa & 17 kDa. In
      contrast, the major component of unlabelled T. trichiura ES, somatic whole worm
      and isolated stichosome extracts, and of [35S]-methionine labelled somatic
      extracts, was present at approximately 47 kDa. Similarly, the major 43 kDa
      protein present in unlabelled T. muris ES, somatic worm extract and [35S]
      methionine labelled somatic worm extract, was only weakly detected in labelled T.
      muris ES. Pulse chase experiments demonstrated that after 20 h, the 43 kDa was a
      prominent component of T. muris ES. These data suggest that the 43/47 kDa protein
      of Trichuris adult worms is not a major constituent of newly synthesized ES but
      is either synthesized at a slower rate than other proteins, or sequestered or
      stored, most likely in the stichocytes, before release. Immunoprecipitations
      using a range of sera from T. trichiura-infected individuals demonstrated that
      many of the ES components are immunogenic. Antibody responses were vigorous in
      children with intense infections and negligible in parasitologically negative
      children. There was marked heterogeneity in responses to a 17 kDa antigen, with
      the age profile of anti-17 kDa antibody levels reflecting age-dependent infection
      intensities at the population level.

PMID- 7731736
TI  - Pathologic indicators of prognosis in endometrial adenocarcinoma. Selected
      aspects emphasizing the GOG experience. Gynecologic Oncology Group.

PMID- 7731737
TI  - Histologic mimics of cutaneous lymphoma.

PMID- 7731738
TI  - Pseudoneoplastic lesions of the oropharynx and larynx simulating cancer.

PMID- 7731739
TI  - Mitotic activity and histological grading of breast cancer.

PMID- 7731740
TI  - Histologic precursors of squamous esophageal cancer.

PMID- 7731741
TI  - Gastrointestinal endocrine cells and carcinoids. Histogenetic and pathogenetic
      considerations.

PMID- 7731742
TI  - The pathology of lysosomal storage diseases.

PMID- 7731743
TI  - Hypersensitivity myocarditis in the explanted hearts of transplant recipients.
      Reappraisal of pathologic criteria and their clinical implications.

PMID- 7731744
TI  - Myelodysplastic syndromes and acute myeloid leukemia. Diagnostic criteria and
      pitfalls.

PMID- 7731745
TI  - Endocrine tumors of the pancreas.

PMID- 7731746
TI  - What's new in placental pathology.

PMID- 7731747
TI  - Inflammatory and other conditions that can mimic carcinoma in the urinary
      bladder.

PMID- 7731748
TI  - Brain cell membrane function during hypoxia in hyperglycemic newborn piglets.
AB  - To test the hypothesis that acute hyperglycemia reduces changes in cell membrane
      structure and function during cerebral hypoxia in the newborn, brain cell
      membrane Na+,K(+)-ATPase activity and levels of membrane lipid peroxidation
      products were measured in four groups of anesthetized, ventilated newborn
      piglets: normoglycemia/normoxia (control, group 1, n = 12),
      hyperglycemia/normoxia (group 2, n = 6), untreated hypoxia (group 3, n = 10), and
      hyperglycemia/hypoxia (group 4, n = 7). Hyperglycemia (blood glucose
      concentration 20 mmol/L) was induced using the glucose clamp technique. The
      hyperglycemic glucose clamp was maintained for 90 min before onset of hypoxia and
      throughout the period of hypoxia. Cerebral tissue hypoxia was induced in groups 3
      and 4 by reducing fraction of inspired oxygen for 60 min and was documented by a
      decrease in the ratio of phosphocreatine to inorganic phosphate as measured using
      31P-nuclear magnetic resonance spectroscopy. Blood glucose concentration during
      hypoxia in hyperglycemic hypoxic animals was 20.7 +/- 1.2 mmol/L, compared with
      10.3 +/- 1.7 mmol/L in untreated hypoxic piglets (p < 0.05). Peak blood lactate
      concentrations were not significantly different between the two hypoxic groups
      (8.4 +/- 2.8 mmol/L versus 7.8 +/- 1.6 mmol/L). In cerebral cortical membranes
      prepared from the untreated animals, cerebral tissue hypoxia caused a 25%
      reduction in Na+,K(+)-ATPase activity compared with normoxic controls and an
      increase in conjugated dienes and fluorescent compounds, markers of lipid
      peroxidation. In contrast, Na+,K(+)-ATPase activity and levels of lipid
      peroxidation products in hyperglycemic hypoxic animals were not significantly
      different from the values in control normoxic animals.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7731749
TI  - Maturation of binocular pattern visual evoked potentials in normal full-term and
      preterm infants from 1 to 6 months of age.
AB  - The purpose of this study was to evaluate the visual development of preterm
      infants from 1 to 6 mo of age, using the pattern visual evoked potentials (VEP)
      in response to three check sizes: 60, 30, and 15 min of arc. Pattern VEP were
      recorded in 24 full-term and 24 preterm infants (26-36 wk of gestation). The
      results showed a rapid visual maturation between 1 and 3 mo, followed by a slower
      progression over the next 3 mo, in both groups. The implicit time of the P100
      wave of the pattern VEP was also found to shorten with increasing check sizes.
      The maturation of pattern VEP in preterm infants was shown to be related to their
      gestational (or corrected) age rather than their postnatal age. The pattern VEP
      obtained in response to a 60-min check size in preterm infants aged between 1.5
      and 2.5 mo (corrected age) showed a tendency for a faster maturation than those
      of full-term infants. Our results suggest that within the first 6 mo of age,
      pattern VEP response is useful to monitor visual development in full-term infants
      as well as in preterm infants using corrected age.

PMID- 7731750
TI  - Regional metabolic assessment of human brain during development by proton
      magnetic resonance spectroscopy in vivo and by high-performance liquid
      chromatography/gas chromatography in autopsy tissue.
AB  - To study the course of regional metabolite concentrations during early brain
      development, we measured in vivo metabolites [N-acetyl-aspartate (NAA), choline
      containing compounds, and myoinositol (M-Ino)] in the precentral area of the
      cerebrum by short echo-time single volume proton magnetic resonance spectroscopy
      and compared in vivo established spectroscopic data with classic chromatographic
      data (HPLC) on age-corresponding autopsy tissue in different regions of the
      brain. In autopsy tissue, regional (frontal lobe, precentral area, basal ganglia,
      thalamus) and age-dependent differences of the concentration of creatine, NAA,
      and M-Ino were determined. In vivo measurement of NAA by proton magnetic
      resonance spectroscopy shows a significant increase of NAA by increasing
      postconceptional age. M-Ino shows a weak correlation and a nonsignificant
      decrease with increasing postconceptional age. Choline shows no age-dependent
      changes. Creatine concentrations measured by HPLC in different regions of the
      developing brain at autopsy showed an age-dependent increase that was identical
      for the left and right side and similar for the precentral area and frontal lobe
      and more pronounced for the basal ganglia and thalamus. Comparison of the results
      obtained by the two methods shows agreement for the age-dependent changes and the
      absolute concentration of M-Ino. NAA determined in autopsy tissue by HPLC is
      significantly lower than that measured in vivo by proton magnetic resonance
      spectroscopy. A comparison of the concentrations measured by HPLC in frontal
      lobe, basal ganglia, and thalamus with the results obtained from the precentral
      area showed significant regional differences in all measured metabolites. These
      results define important age-dependent changes detected with both methods and
      further indicate limitations of both methods that have to be considered when
      presenting absolute concentration values.

PMID- 7731751
TI  - Activation of the neutrophil bactericidal activity for nontypable Haemophilus
      influenzae by tumor necrosis factor and lymphotoxin.
AB  - Previous studies have suggested that, in vivo, activated T lymphocytes and
      neutrophils are important in immunity to nontypable Haemophilus influenzae. We
      now extend this work by showing that neutrophils pretreated with products of
      activated T lymphocytes or activated macrophages show significantly enhanced
      killing of nontypable H. influenzae. Lymphotoxin, a product of activated T
      lymphocytes, significantly enhanced the neutrophil-mediated killing of nontypable
      H. influenzae, and tumor necrosis factor, produced by activated T lymphocytes as
      well as macrophages stimulated by activated T lymphocytes, also significantly
      increased the bactericidal activity of neutrophils. These cytokine-induced
      effects were seen with short pretreatment times of neutrophils and were maximal
      by 30 min. The killing of H. influenzae by neutrophils required the presence of
      heat-labile opsonins. In the absence of these opsonins, both tumor necrosis
      factor and lymphotoxin were unable to promote the killing of the bacteria by
      neutrophils. Furthermore, the results showed that tumor necrosis factor-primed
      neutrophils displayed significantly increased expression of CR3 and CR4 that was
      associated with increased phagocytosis of complement-opsonized nontypable H.
      influenzae. These cytokines may play an important role in immunity toward
      nontypable H. influenzae by stimulating neutrophil bactericidal activity.

PMID- 7731752
TI  - Sequence analysis of the tumor necrosis factor gene in pediatric patients with
      autoimmunity.
AB  - Tumor necrosis factor-alpha (TNF) is a multifunctional protein hormone that
      contributes to host defense and perinatal immunologic development. Dysregulated
      TNF production, however, occurs during the pathogenesis of autoimmune diseases
      and may be inherent to their development. In animal models of autoimmunity,
      dysregulated TNF synthesis has resulted from mutations in TNF gene regulatory
      sequences, specifically those sequences involved in translational control of TNF
      gene expression. In this study, we have determined whether mutations in the TNF
      translational control sequences are present in pediatric patients with type I
      diabetes mellitus and connective tissue diseases. Blood samples were collected
      from 48 patients with connective tissue diseases, 32 patients with diabetes, and
      29 controls. A 250-bp fragment of the translational control sequences present in
      the TNF 3'-untranslated region was amplified by the polymerase chain reaction,
      sequenced, and analyzed relative to the published TNF sequence. In this study,
      all patients and controls exhibited the normal sequence, with no insertions or
      deletions in the translational control motifs. We conclude that polymorphisms in
      the TNF 3'-untranslated region occur infrequently, if at all, in patients with
      diseases examined here.

PMID- 7731753
TI  - An immunologic approach to induction of epidermal growth factor deficiency:
      induction and characterization of autoantibodies to epidermal growth factor in
      rats.
AB  - Epidermal growth factor (EGF) in pharmacologic doses is able to induce growth and
      development in the fetus and the newborn. To investigate the opposite situation,
      the effects of insufficient amounts of EGF during development, we wanted to
      establish an in vivo model with a state of EGF deficiency. This was attempted by
      induction of autoimmunity to EGF in rats. Twenty rats were immunized with EGF.
      Fifteen of these developed autoantibodies against EGF, which, as judged by
      Scatchard analysis, had a median apparent affinity constant of 14 x 10(9) L/mol
      and a median concentration of binding sites of 20 x 10(-9) mol/L. The antibodies
      recognized purified EGF from the submandibular glands (6 kD) and from urine (45
      kD) and further native EGF in saliva and urine. The cross-reactivity toward
      transforming growth factor-alpha was below 3%. Binding of EGF by antibodies
      inhibited its binding to the EGF-receptor by approximately 97% in vitro.
      Investigation of in vivo metabolism of antibody-bound 125I-EGF confirmed these
      results, that is, the antibodies were able to inactivate EGF. The adult rats were
      unaffected by the induction and presence of autoantibodies, and the EGF
      containing organs did not show any histologic signs of inflammation or tissue
      damage. Furthermore, as judged by immunohistochemistry, no major changes in the
      distribution and tissue concentration of EGF were seen in the adult rat. These
      results show that it is possible to induce homologous antibodies that can inhibit
      the binding of EGF to its receptor and further suggest that circulatory EGF is of
      no physiologic importance in the healthy, adult rat.

PMID- 7731754
TI  - Fetal effects of epidermal growth factor deficiency induced in rats by
      autoantibodies against epidermal growth factor.
AB  - We have used rats with epidermal growth factor (EGF) autoantibodies to study the
      role of EGF deficiency during perinatal development. The study was focused on
      organs known to contain EGF or its receptor. Compared with controls, the
      offspring of autoimmune rats had a higher perinatal mortality and a lower birth
      weight. The weight of the lungs was particularly low in the offspring of EGF
      immunized rats, and morphologically the lungs from the surviving pups seemed
      atelectatic and had alveolar duct dilatation, which indicates mild respiratory
      distress syndrome. Judged from immunohistochemical studies, the amount of
      surfactant protein-A was decreased, suggesting a delayed lung maturation. The
      offspring of EGF-immunized rats had dry and wrinkled skin. The skin was thin and
      the hair follicles were immature. This suggests a role for EGF in the growth and
      development of the skin. The liver/body weight ratio was lower in pups from EGF
      immunized rats. This difference was, however, not significant (p = 0.07), but
      flow cytometric analyses showed a significantly lower proportion of the liver
      cells from newborn EGF-deficient pups to be in S-phase and indicated that these
      cells were larger than liver cells from controls. To study possible alterations
      in EGF binding, 125I-EGF was injected i.v. in newborn rats. 125I-EGF bound in all
      the organs investigated. The binding is listed in decreasing order: liver, gut,
      skin, kidney, and lungs. In the pups from EGF-immunized rats, the lungs and the
      skin bound a significantly higher amount than the controls.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7731755
TI  - Myocardial energy metabolism in the newborn lamb in vivo during pacing-induced
      changes in oxygen consumption.
AB  - Myocardial energy metabolism was studied in newborn sheep to determine whether
      the metabolic responses to pacing-induced increases in heart rate were similar to
      those previously found during catecholamine stimulation. Open-chest newborn
      sheep, 3 to 9 d old (n = 11), underwent atrial pacing at a respiratory rate
      harmonic just above the intrinsic heart rate. Pacing rate was increased by 30
      beats/min every 5 min until conduction block or a drop in systemic arterial
      pressure occurred. Phosphorous metabolites were monitored simultaneously (n = 7)
      using a 31P magnetic resonance surface coil over the heart within a magnet
      operating at 4.7 tesla. Myocardial oxygen consumption was monitoring via an
      extracorporeal shunt from the coronary sinus. Rate pressure product increased
      with heart rate and was found to relate to myocardial oxygen consumption (r =
      0.75), which increased maximally by 47 +/- 9% due to increases in coronary blood
      flow. Phosphocreatine/ATP ratio decreased significantly, and calculated ADP
      increased between baseline and peak performance but returned to near baseline
      levels during recovery at the initial pacing rate. These findings indicate that
      intracellular high-energy phosphate concentrations do change with alterations in
      myocardial oxygen consumption induced by cardiac pacing in the newborn. These
      changes are similar to those found during epinephrine infusion. Furthermore, the
      ATP hydrolysis products probably participate in myocardial respiratory regulation
      in the newborn in vivo.

PMID- 7731756
TI  - Cell-specific expression of fibronectin in adult and developing rabbit lung.
AB  - Fibronectin (FN), a glycoprotein component of the extracellular matrix, plays a
      role in tissue morphogenesis and tissue-specific differentiation through its
      effects on cell adhesion, cell shape, and cytoskeletal organization.
      Immunohistochemistry has been used to show that during lung development FN
      deposition changes, yet the cell-specific sites of pulmonary FN synthesis have
      not been determined. Because cellular FN synthesis is reflected by FN mRNA
      abundance, we performed in situ hybridizations to identify pulmonary tissue with
      the capacity to synthesize FN. Both in situ mRNA hybridization and
      immunohistochemical staining were performed on tissue sections from lungs of
      adults and late gestation fetal and neonatal rabbits. In adults, FN transcripts
      and immunostaining were clearly seen in endothelial cells, smooth muscle cells,
      and chondrocytes. During lung development, FN transcripts were virtually
      ubiquitous except in airway epithelium. There was a gradual decrease in FN mRNA
      abundance with advancing fetal age, but low levels of FN mRNA persisted in
      neonatal and adult lungs. In contrast, parenchymal immunostaining increased
      throughout fetal development and remained elevated in the newborn. FN
      immunostaining was lower in adult lung. In all tissues examined, airway
      epithelial cells contained no FN transcripts above background. However,
      immunostaining was detected in airway basement membrane zones and on luminal
      surfaces of some epithelial cells. The lack of FN transcripts in airway
      epithelial cells suggests that FN synthesis does not normally occur in this cell
      type and that its associated FN immunostaining is from another source. The
      colocalization of FN mRNA and protein in pulmonary endothelial cells, smooth
      muscle cells, and chondrocytes in adults strongly suggests that these cells are
      sites of FN synthesis.

PMID- 7731757
TI  - The myogenic response of arterial vessels is increased in fetal pulmonary
      hypertension.
AB  - The stretch-induced myogenic response (MR) of large-capacitance pulmonary
      arteries were studied in normal and pulmonary hypertensive fetuses as well as
      normal newborn and adult sheep. Pulmonary hypertension in the fetus was induced
      by ligation of the ductus arteriosus for 12 d. The MR was obtained by stretching
      the vessel segments in vitro from their resting diameter (no load) to the
      diameter at which the muscle fibers were at optimal length (Lo), and the response
      was measured as a percentage of force obtained after supramaximal electrical
      stimulation (Po). In five control and four pulmonary hypertensive fetuses, the MR
      was also obtained after a stretch of 140% of Lo. The pulmonary hypertensive fetal
      arteries had a lower stress (1.3 +/- 0.4 versus 4.0 +/- 0.5 mN/mm2; p < 0.001)
      and shortening capacity compared with the fetal control (5.1 +/- 1.6 versus 9.9
      +/- 0.8% of Lo; p < 0.01). The MR was observed in 21% of the control and 30% of
      the experimental fetuses, and it was of greater magnitude in the latter (14.8 +/-
      1.9 of Po versus 34.3 +/- 2.5%, respectively; p < 0.01). When stretched to 140%
      of Lo, the MR was also greater in the experimental (514 +/- 148% of Po) than the
      control fetuses (142 +/- 68; p < 0.05). Postnatally, the MR was present in 67% of
      the newborn and 15% of the adult pulmonary artery segments, and the response was
      greatest in the newborn (23.1 +/- 4.2% of Po) compared with the adult (2.3 +/-
      0.8; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731758
TI  - Characterization of actin and myosin in the developing stomach.
AB  - During growth and development, dietary intake changes from being predominantly
      liquid in the newborn period to mixed solid liquid meals. These alterations in
      diet vary the functional demands placed on the stomach. It has been shown that,
      during development, smooth muscle of the stomach undergoes changes in the
      mechanism responsible for the contractile process. In this study, we have
      investigated the possibility that there are structural changes in two of the
      major proteins that are responsible for generation of force during smooth muscle
      contraction: actin and myosin. Actin and myosin were identified in newborn
      kittens (1 wk old) and adult gastric smooth muscle using one-dimensional SDS
      PAGE. Although both the antrum and fundus of the kitten have significantly
      smaller total amounts of actin and myosin per mg protein than the adult, the
      ratio of actin to myosin is not significantly different between the age groups.
      Two different myosin heavy chain (MHC) isoforms, MHC1 (205 kD) and MHC2 (200 kD),
      were identified in all tissues. The relative amount of MHC1 remained constant
      during maturation of the stomach. We observed an increase in the amount of MHC2
      in the adult, which resulted in a decreased ratio of MHC1 to MHC2 in the adult.
      We postulate that the decreased quantity of actin and myosin in the kitten
      stomach and the observed changes in the ratio of the MHC isoforms are related to
      changes in the gastric motor that occur during growth and development.

PMID- 7731759
TI  - The prenatal development and glucocorticoid control of brush-border hydrolases in
      the pig small intestine.
AB  - The development of brush-border enzymes and the possible regulatory role of
      cortisol were investigated in the small intestine of the fetal and neonatal pig.
      With the sows under pentobarbitone anesthesia, osmotic minipumps containing
      either saline or cortisol were inserted s.c. into 25 fetuses from 10 pregnant
      sows (82-96 d gestation). Six d later, the infused fetuses were removed by
      cesarean section and samples of the proximal, middle, and distal intestine taken
      for analysis. Samples were also obtained from 48 piglets that did not undergo an
      operation (controls) and that were removed at intervals from 82 d gestation until
      term (114 +/- 2 d). In the proximal and middle intestine, the mean levels of
      lactase-phlorizin hydrolase (EC 3.2.1.23-62), maltaseglucoamylase (EC 3.2.1.20),
      aminopeptidase N (EC 3.4.11.2), and aminopeptidase A (EC 3.4.11.7) increased
      during the last 10-15 d before term, correlated positively with log10 plasma
      cortisol values, and were higher in cortisol-infused than in saline-infused
      fetuses (p < 0.05). Activity of sucrase-isomaltase (EC 3.2.1.48-10) was low in
      fetal pigs, and this enzyme and dipeptidyl peptidase IV (EC 3.4.14.5) were not
      significantly affected by fetal age or exogenous cortisol. Maltase (EC 3.2.1.48
      10 and EC 3.2.1.20) activity was significantly decreased in the middle and distal
      intestine of cortisol-infused fetuses. The results suggest that the prepartum
      rise in endogenous cortisol secretion stimulates the prenatal expression of
      certain brush-border enzymes in the pig small intestine at this critical time.
      However, the effects of cortisol on the developing intestine were highly
      idiosyncratic for particular enzymes and intestinal regions.

PMID- 7731760
TI  - Low incidence of childhood celiac disease in The Netherlands.
AB  - The incidence and prevalence of celiac disease vary internationally. We studied
      the incidence of identified cases of childhood celiac disease in six Dutch
      provinces that cover 47.9% of the surface area and 67.6% of the total population
      of The Netherlands. Children with celiac disease aged 0-14 y, diagnosed from
      January 1975 to January 1991, were traced by 1) contacting all pediatricians in
      this area, 2) examining the date of the Dutch National Medical Registration, and
      3) investigating the membership records of the Dutch Celiac Disease Society.
      These data were cross-checked by the Dutch Network and National Database of
      Pathology. Of the 97.9% of pediatricians who answered our inquiry, 46.1% were
      treating celiac patients. A total of 342 celiac patients were identified.
      Informed consent that permitted examination of their medical files was given by
      97.3% of the parents of the celiac children. The mean crude incidence rate of
      diagnosed childhood celiac disease, calculated per 1000 live births per year, was
      0.18. However, a significant increase in reported incidence was demonstrated from
      0.10 in 1976 to 0.32 in 1990. The best estimate, for the years 1985-1990, is
      0.22/1000 live births, which is much lower than in most European countries.

PMID- 7731761
TI  - Plasma copper and antioxidant status in Wilson's disease.
AB  - It has been demonstrated that the level of serum copper unbound to ceruloplasmin
      (loosely bound copper) is increased in Wilson's disease, although the total serum
      copper concentration is usually low, reflecting a low ceruloplasmin level. To
      assess the contribution of free radical reactions catalyzed by nonceruloplasmin
      copper to the development of complications in this disease, we investigated
      copper and antioxidant status in four untreated patients who had hepatic
      dysfunction with or without hemolytic anemia and made a comparison with five
      patients controlled on penicillamine therapy and 19 age-matched healthy children.
      We found that loosely bound copper in plasma measured by the phenanthroline assay
      was detectable in three of four untreated patients with Wilson's disease, but was
      not detectable in the patients during therapy or in the healthy controls. Among
      the various antioxidants, the ascorbate and urate levels were markedly reduced
      before treatment (mean +/- SD, 23 +/- 16 microM for ascorbate and 90 +/- 59
      microM for urate) compared with the values in the patients during treatment with
      penicillamine (67 +/- 19 and 302 +/- 78 microM, p < 0.05) and in control children
      (60 +/- 8 and 254 +/- 48 microM, p < 0.05). We also demonstrated that the plasma
      concentration of allantoin, an oxidation product of uric acid and a possible
      marker of radical generation in vivo, was markedly elevated in the untreated
      patients (11.0 +/- 1.8 versus 4.3 +/- 0.5 microM in patients on therapy and 6.5
      +/- 0.8 microM in controls, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731762
TI  - Water loss from the skin of term and preterm infants nursed under a radiant
      heater.
AB  - The rate of evaporation from the skin (g/m2/h) was measured in 12 full-term and
      16 preterm infants (gestational age 25-34 wk) both during incubator care and when
      nursed under a radiant heater. The method for evaporation rate measurement is
      noninvasive and based on determination of the water vapor pressure gradient close
      to the skin surface. Measurements were first made with the infant nursed in an
      incubator with a controlled environment with respect to humidity, temperature,
      and air velocity. The measurements in the term infants were performed at an
      ambient relative humidity (RH) of 50%, and in the preterm infants first at 50%
      and subsequently at 30-40%. Evaporation rate was then measured with the infant
      nursed under a radiant heater. In term infants, mean evaporation rate was 3.3
      g/m2/h during incubator care (RH 50%) and 4.4 g/m2/h during care under the
      radiant heater. In preterm infants, the corresponding values were 15.5 g/m2/h in
      the incubator at RH 50%, 16.7 g/m2/h at RH 30-40%, and 17.9 g/m2/h under the
      radiant heater. It is concluded that the evaporative water loss from the skin
      depends on the ambient water vapor pressure, irrespective of whether the infant
      is nursed in an incubator or under a radiant heater. The higher rate of
      evaporation during care under a radiant heater is due to the lower ambient water
      vapor pressure and not to any direct effect of the nonionizing radiation on the
      skin.

PMID- 7731763
TI  - For how long is exclusive breast-feeding adequate to satisfy the dietary energy
      needs of the average young baby?
AB  - This review is based on a lecture given in connection with the 1994 Nutricia
      Foundation Award. It describes how recent research findings in infant dietary
      energy requirements have provided a firm quantitative basis for the widely quoted
      pediatric view that exclusive breast-feeding should provide sufficient
      nourishment for the average child until 4-6 mo of age.

PMID- 7731764
TI  - In vivo measurement of phenylalanine in human brain by proton nuclear magnetic
      resonance spectroscopy.
AB  - Disorders of the CNS are the major causes of morbidity and mortality observed in
      untreated subjects with phenylketonuria (PKU). A method to measure cerebral
      concentrations of phenylalanine (Phe) in vivo would greatly enhance the ability
      to investigate both the pathophysiology and the efficacy of therapy of this
      aminoacidopathy. Twelve image-guided localized proton nuclear magnetic resonance
      spectroscopic studies were performed in seven subjects with PKU using pulse
      sequences optimized to detect the aromatic protons of Phe. Ten control studies
      were also performed using a 2.1-Tesla Bruker Biospec spectrometer. Plasma Phe was
      measured at the time of the spectroscopic examination in the PKU patients. A Phe
      signal was observed in all 12 studies performed on the group with PKU, and in
      five studies cerebral Phe concentrations were measured to be 480 to 780 mumol/g.
      Plasma Phe concentrations were 0.7 to 3.3 mM (10.8 to 54.8 mg/dL) in the subjects
      with PKU. Human cerebral Phe concentrations can be measured noninvasively using
      proton nuclear magnetic resonance spectroscopy. A simultaneous measure of Phe and
      several other cerebral metabolites is obtained with this innovative technology.
      Adaptations of this technique can be used to investigate PKU and other
      neurometabolic disorders with modifications of current clinical magnetic
      resonance imaging systems.

PMID- 7731765
TI  - [Clinical analysis of 130 cases of Siberian silicosis].
AB  - One hundred thirty patients with Siberian silicosis occurring under exposure to
      large amounts of dust at labor in a siberian mine were analyzed for 67 clinical
      and 122 laboratory data. Eighty-eight of 130 patients are now alive, but 42 have
      already died. When they started work, 122 of the patients were under thirty years
      of age. The duration of work was 7 to 12 months for 17 patients, 13 to 18 for 43,
      and 19 to 24 for 40. Seventy-six of 99 patients were initially diagnosed with
      lung tuberculosis and 23 with silicosis. Almost all patients have complained of
      respiratory symptoms such as shortness of breath, cough, sputum, and cyanosis.
      All of the pulmonary function tests including %VC, FEV1.0/FVC, V25/height, RV,
      TLC, and DLco showed abnormal values. The chest roentogenograms showed 3 of type
      1, 22 of type 2, 55 of type 3, and 124 of type 4. Of 124 type-4, large opacities,
      84 were type A, 28 B, and 12 C. Of 416 small opacities, 144 were type P, 191 Q,
      and 81 R. The complications and secondary changes that appeared with progression
      of the disease were lung emphysema, hilar and mediastinal lymphnode enlargement,
      egg shell calcification in lymphnode, and bulla or bleb.

PMID- 7731766
TI  - [Physical properties of Strecker stents].
AB  - Strecker stent is a balloon-expandable metallic stent that is made of knitted
      tantalum wire mesh in order to Maintain flexibility. Therefore, the prosthesis is
      well suited to irregular and tortuous tube organs. We performed several physical
      experiments using 8 mm and 6 mm diameter stents made of 0.1 mm diameter wire
      filament. The bearing power of the 8 mm diameter stent against the
      circumferential compression pressure was divided into two groups, that is, 77
      100% and under 66% of expansile rate. The capacity bearing the circumferential
      compression pressure of the latter group was greater than that of the former.
      Further, the bearing power of the 6 mm diameter stent was greater than that of
      the 56% expansile rate of the 8 mm diameter stent. The smaller the expansile rate
      of the stent, the smaller the minimum radius of curvature within the limits of
      the stent's plastic. To evaluate the suitability of the stent in clinical use, we
      made two projections on the inner surface of rubber tubes, and the stents were
      placed into the rubber tubes at different expansile rates. We evaluated the
      degree of contact of the stents against the rubber wall by taking soft X-ray
      photographs. The stents showed good suitability under the condition of incomplete
      expansion. For the above reasons, we concluded that, from the view-point of
      bearing power, the stent should be placed in the full expansile state. From the
      viewpoint of contact against the vessel wall, the stent should be placed in the
      incomplete expansile state.

PMID- 7731767
TI  - [Comparison between T2*- and T2-weighted images in diagnosing rotator cuff
      tears].
AB  - This study was performed to determine the merits of T2*-weighted images in
      diagnosing rotator cuff tear, compared with T2-weighted images. T2-and T2*
      weighted images were obtained in 10 asymptomatic volunteers and 94 patients with
      symptoms referable to the rotator cuff. The increased signal with full thickness
      of the rotator cuff was not shown on either T2- or T2*-weighted images in the
      volunteers. These findings on T2-weighted images and on T2*-weighted images were
      observed in 33 and 58 of 94 patients with symptoms, respectively. Every patient
      who showed these abnormal findings on T2-weighted images had the abnormal
      findings on T2*-weighted images. These findings on T2*-weighted images were wider
      than those on T2-weighted images in 20 of 33 patients. Surgical findings were
      available in 21 of 94 patients. Rotator cuff tears were surgically confirmed in
      20 patients whose MR images showed increased signal lesions on both T2- and T2*
      weighted images. On the other hand, one patient who did not have rotator cuff
      tear showed increased signal lesion with full thickness on T2*-weighted images,
      but not on T2-weighted images. We think increased signal lesions on T2-weighted
      images may strongly suggest rotator cuff tear, whereas those on T2*-weighted
      images are not specific.

PMID- 7731768
TI  - [Optimal concentration of contrast medium in helical CT of the thorax].
AB  - In 99 examinations of 89 patients, we took CT images of the chest after
      administering one of three concentrations of contrast medium (iohexol 140 mgI/ml,
      240 mgI/ml, 300 mgI/ml) to determine the optimal iodo-concentration for
      intravenous contrast enhancement in spiral CT. Attenuation values of the superior
      vena cava, ascending aorta, descending aorta, and pulmonary artery were measured
      to evaluate the degree of contrast enhancement. Five radiologists judged the
      image quality by scoring factors such as vascular opacification, delineation of
      the lung and chest wall, detectability of calcification, lymphadenopathy and
      pulmonary nodules, and the presence of artifacts. The relationships between the
      iodo-concentration and the scores were analyzed statistically. The higher the
      iodo-concentration of the contrast medium administered, the stronger the vascular
      structures were opacified. There was also a concurrent improvement in the
      detection of lymphadenopathy. However, artifacts appeared on the administration
      route as a result of the high-concentration contrast medium, and the image
      quality was degraded. Among the three groups, iohexol 240 mgI/ml exhibited the
      best performance, namely, good image quality, so that a high degree of contrast
      enhancement of the vasculature was obtained with few artifacts due to the
      contrast medium. However, we believe that iohexol 140 mgI/ml presents no
      significant problems in routine studies.

PMID- 7731769
TI  - [A case of adenomyelolipoma].
AB  - We report case of adenomyelolipoma. CT and MRI revealed a large, capsulated,
      septated adrenal mass with abundant fat tissue. However, enhancing components
      were demonstrated at the capsule and septations on angiography. On the
      pathological study, the capsule and septations consisted of adrenal adenoma and
      the tumor contained various forms of myelolipomatous tissues. These
      myelolipomatous tissues were classified into 4 groups. Type I: Scattering of fat
      cells and hematopoietic elements without coalescence. Type II: Collection of
      myelolipomatous tissue with unclear margin or small myelolipomatous tissue that
      cannot be classified as type I or III. Diameter of the lesion is less than 1 cm.
      Type III: Collection of myelolipomatous tissue with clear margin or replacement
      of cortical nodule. Diameter of the lesion is less than 1 cm. Type IV: Collection
      of myelolipomatous tissue. Diameter of the lesion is equal to or greater than 1
      cm. We defined adenomyelolipoma as a lesion combining adrenal adenoma (or
      hyperplasia) and various forms of myelolipomatous tissues (type I-IV) in view of
      the strong relationship between adrenal adenoma (or hyperplasia) and
      myelolipomatous tissue.

PMID- 7731770
TI  - Pulmonary abnormalities caused by interferon with or without herbal drug: CT and
      radiographic findings.

PMID- 7731771
TI  - [Evaluation of sleep apnea syndrome (SAS) with low field MR fluoroscopy].
AB  - Eight cases of clinically diagnosed sleep apnea syndrome (SAS) and two normal
      volunteers were studied with low field MR fluoroscopy in order to monitor the
      waking and sleeping status of the upper airway. MR fluoroscopy revealed that only
      the sleeping patients showed occlusions of the upper airway. This technique
      provided us with useful information about the level, frequency and duration of
      occlusion in each case. Four of the eight patients demonstrated simple
      retropalatal occlusion, whereas the other four demonstrated mixed retropalatal
      and retropalato-retroglossal occlusion. Thus long-time monitoring, which is only
      possible with MR fluoroscopy, is needed to appreciate the complex nature of the
      disease. In addition, the comfortable surroundings and low noise level provided
      by the low field enabled physiological study to be performed without any
      tranquilizers in most of the patients, which is again only possible with MR
      fluoroscopy. MR fluoroscopy may become a tool of great clinical value, providing
      much important information for disease evaluation and treatment selection.

PMID- 7731772
TI  - [MR diagnosis for metastasis or non-metastasis of mediastinal and hilar lymph
      nodes in cases of primary lung cancer: detectability, signal intensity, and MR
      pathologic correlation].
AB  - The detectability and signal intensity on MR imaging of mediastinal and hilar
      lymph nodes were studied in cases of lung cancer. Additionally, short inversion
      time inversion recovery (STIR) images and pathologic findings were compared. In
      the detection of resected metastatic mediastinal and hilar lymph nodes (n = 146),
      the STIR image (82%) was superior to the T1-weighted image (71%) and the T2
      weighted image (60%). On STIR imaging, 212 (60%) of 412 resected non-metastatic
      mediastinal nodes and 38 (33%) of 116 resected non-metastatic hilar lymph nodes
      were detected. Characteristics of signal intensities of metastatic nodes were
      mainly low on T1-weighted images, high on T2-weighted images, and very high on
      STIR images. The rate of these characteristics of signal intensity of metastatic
      nodes was 59%. However, the rate of very high signal intensity of metastatic
      nodes on STIR imaging was 81%. Pathologically, lymph nodes with high or very high
      signal intensities on STIR images were metastatic, reactive and hyperplastic, or
      non-metastatic. Lymph nodes with slightly high signal intensity or high intensity
      with a low focus on STIR images were anthracotic, anthrasilicotic, caseous
      necrotic, calcified, or fibrotic. Thus, when the signal intensity of a lymph node
      was decreased on the STIR image, there was no definite evidence of metastasis
      excluding micro-metastasis or coagulation necrosis of a metastatic tumor. We
      conclude that the signal characteristics on STIR imaging are useful for
      distinguishing between macro-metastatic and non-metastatic lymph nodes when
      enlarged nodes are detected by various other types of medical imaging.

PMID- 7731773
TI  - [A pilot study with lung-cancer screening CT (LSCT) at the secondary screening
      for lung cancer detection].
AB  - We have developed computed tomography (CT) equipment for lung-cancer screening
      (named LSCT) that can be used exclusively for lung-cancer screening with spiral
      volumetric CT and is available on a screening car. A pilot study with LSCT was
      performed from November 1992 to January 1993 on 118 screenees at the secondary
      examination of lung-cancer screening. Scan parameters were as follows: 120 kVp,
      50 mA, slice thickness 10 mm, table feed 10 mm/sec, scan time 2 sec/rotation. All
      the screenees were scanned under quiet respiration instead of the breath-hold
      technique. Under these scan parameters, LSCT images were almost free from
      respiratory motion artifacts even at the lung base. Continuity of the bronchial
      tree and vessels was well maintained in consecutive slices. Pulmonary nodules
      approximately 5 mm in diameter were clearly depicted. By LSCT, 43 of 118
      screenees were diagnosed to need further examinations. And 33 out of 43 screenees
      underwent detailed examinations. Finally, 16 lung cancers were confirmed. Ten of
      16 patients with lung cancer underwent surgery; nine were in stage I and one in
      stage IIIA. LSCT was considered to be useful in lung-cancer screening.

PMID- 7731774
TI  - [Indications for chest CT: retrospective study of cases with normal chest CT].
AB  - The usefulness of computed tomography (CT) in thoracic radiology is now well
      appreciated, and the number of chest CTs has greatly increased. There are,
      however, many chest CT cases that are completely or almost completely normal.
      Indications for chest CT should be re-evaluated considering the cost and
      radiation exposure associated with the examination. Reviewing the reports of 4930
      chest CT examinations performed in three hospitals during the period of two
      years, the author found 620 (12.6%) negative CT examinations. In 312 of the 620,
      the CT was requested because of "abnormal shadow" on chest radiograph. When the
      same chest radiographs were re-evaluated by two radiologists, no abnormality was
      noted in 257 cases (82.4%). CT examinations were considered justified in only 55
      cases (17.6%). There was a significant difference in the frequency of normal
      chest CT examinations between the university hospital and two other hospitals.
      The causes of false positive interpretation of chest radiographs were analyzed,
      and it was felt that fundamental knowledge necessary to interpret chest
      radiographs was lacking. The importance of close cooperation between clinicians
      and radiologists should be emphasized.

PMID- 7731775
TI  - [Spatial and temporal alteration of the dual supply of the hepatic circulation
      with transient occlusion of the hepatic veins: spiral volumetric CT during
      arterial portography and arteriography].
AB  - To elucidate the contribution of hepatic veins to the blood flow of liver, CT
      arterial portography and/or arteriography was performed in eight patients having
      hepatocellular carcinoma with transient occlusion of the hepatic vein and eight
      without occlusion. In each patient with occlusion of the hepatic vein, CT showed
      a well-demarcated fan-shaped area of low density during arterial portography and
      increased density during arteriography in the corresponding area. Hepatic vein
      occlusion could result in the pooling of arterial blood in the liver parenchyma.
      Transient segmental hepatic venous occlusion might improve the results of
      transcatheter arterial infusion and transcatheter arterial embolization for liver
      tumors.

PMID- 7731776
TI  - [Transjugular intrahepatic portosystemic shunt for patients with hepatoma].
AB  - Nine patients with hepatoma, 5 with massive ascites, 3 with rupture of esophageal
      varices and 1 with hematoemesis, successfully underwent TIPS without technical
      complications. Two of the patients died 3 and 5 months, respectively, after TIPS
      due to hepatic failure and/or tumor extension. Another patient in whom hepatoma
      ruptured 1 month after TIPS was experienced. It is concluded that TIPS is a
      useful and safety treatment for portal hypertension even in patients with
      hepatoma which was not existed through the puncture route. However TIPS should be
      performed in patients in whom hepatoma has been controlled by hepatic
      embolization and/or ethanol injection therapy.

PMID- 7731777
TI  - [Effect of copper and copper binding protein on the CT attenuation value of
      liver: experimental study in rats].
AB  - We analyzed the effect of copper and copper binding protein on CT attenuation
      value in a rat model. CT attenuation values of the liver were compared with
      hepatic copper content and grade of orcein-positive granules, which are thought
      to be a counterpart of polymerized methalothionein in lysosomes. The difference
      between hepatic copper and CT attenuation value was not statistically significant
      (R = 0.056, p = 0.96). CT value had a positive correlation with the grade of
      orcein-positive granules (Rho = 0.755, p = 0.0001). We concluded that the CT
      attenuation value of liver can be elevated by rich polymerized methalothionein
      (copper binding protein) in lysosomes.

PMID- 7731778
TI  - Delegation of selected nursing tasks.

PMID- 7731779
TI  - New Jersey State Nurses Association Position Statement on Minority Health.

PMID- 7731780
TI  - A-1669: HIV testing of pregnant women.

PMID- 7731781
TI  - Fewer nurses to answer the buzzer.

PMID- 7731782
TI  - In my opinion....

PMID- 7731783
TI  - Food addiction.

PMID- 7731784
TI  - New Jersey State Nurses Association Position Statement on Prenatal HIV Testing.

PMID- 7731785
TI  - Supreme Court decision questions employment status of nurses.

PMID- 7731786
TI  - HIV/AIDS and related issues forum: call for speakers.

PMID- 7731787
TI  - Patient teaching in home care.

PMID- 7731788
TI  - PARP promoter-mediated activation of a VSG expression site promoter in insect
      form Trypanosoma brucei.
AB  - In trypanosomes the rRNA, PARP and VSG gene promoters mediate alpha-amanitin
      resistant transcription of protein coding genes, presumably by RNA polymerase
      (pol) I. We compared the activity of PARP and VSG promoters integrated at one of
      the alleles of the largest subunit of pol II genes in insect form trypanosomes.
      Even though both promoters are roughly equally active in transient transformation
      assays in insect form trypanosomes, only the PARP promoter functioned effectively
      when integrated at the pol II largest subunit or other loci. Promoter activity in
      transient transformation assays is therefore not necessarily predictive of
      transcriptional activity once integrated into the trypanosome genome. The
      integrated fully active PARP promoter could upregulate in cis an otherwise poorly
      active integrated VSG promoter. The PARP promoter nucleotide sequence elements
      responsible for VSG promoter activation coincided with most of the important PARP
      promoter elements mapped previously by linker scanning mutagenesis, indicating
      that it is not a single unique promoter element that was responsible for VSG
      promoter activation. The data suggest that PARP promoter-mediated activation of
      the VSG promoter does not result from complementation of the VSG promoter with a
      single insect form-specific transcription factor whose binding site is missing
      from the VSG promoter and present in the PARP promoter. We favor a model in which
      chromatin structure at the locus is altered by the PARP promoter, allowing VSG
      promoter activation in insect form trypanosomes. We discuss the significance of
      these observations for the control of VSG promoters in insect form trypanosomes.

PMID- 7731789
TI  - Homology model building of the HMG-1 box structural domain.
AB  - Nucleoproteins belonging to the HMG-1/2 family possess homologous domains
      approximately 75 amino acids in length. These domains, termed HMG-1 boxes, are
      highly structured, compact, and mediate the interaction between HMG-1 box
      containing proteins and DNA in a variety of biological contexts. Homology model
      building experiments on HMG-1 box sequences 'threaded' through the 1H-NMR
      structure of an HMG-1 box from rat indicate that the domain does not have rigid
      sequence requirements for its formation. Energy calculations indicate that the
      structure of all HMG-1 box domains is stabilized primarily through hydrophobic
      interactions. We have found structural relationships in the absence of
      statistically significant sequence similarity, identifying several candidate
      proteins which could possibly assume the same three-dimensional conformation as
      the rat HMG-1 box motif. The threading technique provides a method by which
      significant structural similarities in a diverse protein family can be
      efficiently detected, and the 'structural alignment' derived by this method
      provides a rational basis through which phylogenetic relationships and the
      precise sites of interaction between HMG-1 box proteins and DNA can be deduced.

PMID- 7731790
TI  - Orphon spliced-leader sequences form part of a repetitive element in
      Angiostrongylus cantonensis.
AB  - In nematodes, the 22 nucleotide (nt) spliced leader (SL) is normally encoded by a
      multi-copy, tandemly reiterated SL gene and is trans-spliced from SL-RNA onto the
      5' end of a subset of mRNAs. We have found that the SL is also encoded at
      multiple (> 100) orphon genomic sites in the parasitic nematode Angiostrongylus
      cantonensis. At these sites the sequence forms part of a 198 bp repetitive
      element (designated con-198). Transcription from two genomic elements that
      contain the con-198 sequence has been characterised. At one element (G-2) an
      approximately 850 nt RNA with an internal SL is transcribed. At the other (G-1),
      transcription takes place 3 kb downstream of the con-198 sequence.

PMID- 7731791
TI  - A modified single-strand annealing model best explains the joining of DNA double
      strand breaks mammalian cells and cell extracts.
AB  - The joining of DNA double-strand breaks in vivo is frequently accompanied by the
      loss of a few nucleotides at the junction between the interacting partners. In
      vitro systems mimic this loss and, on detailed analysis, have suggested two
      models for the mechanism of end-joining. One invokes the use of extensive
      homologous side-by-side alignment of the partners prior to joining, while the
      other proposes the use of small regions of homology located at or near the
      terminus of the interacting molecules. to discriminate between these two models,
      assays were conducted both in vitro and in vivo with specially designed
      substrates. In vitro, molecules with limited terminal homology were capable of
      joining, but analysis of the junctions suggested that the mechanism employed the
      limited homology available. In vivo, the substrates with no extensive homology
      end-joined with equal efficiency to those with extensive homology in two
      different topological arrangements. Taken together, these results suggest that
      extensive homology is not a prerequisite for efficient end-joining, but that
      small homologies close to the terminus are used preferentially, as predicted by
      the modified single-strand annealing model.

PMID- 7731792
TI  - Analysis of CYS3 regulator function in Neurospora crassa by modification of
      leucine zipper dimerization specificity.
AB  - The CYS3 positive regulator is a basic region-leucine zipper (bZIP) DNA-binding
      protein that is essential for the expression of sulfur-controlled structural
      genes in Neurospora crassa. An approach of modifying the dimerization specificity
      of the CYS3 leucine zipper was used to determine whether the in vivo regulatory
      function of CYS3 requires the formation of homodimeric or heterodimeric
      complexes. Two altered versions of CYS3 with coiled coil elecrostatic
      interactions favorable to heterodimerization showed restoration of wild-type CYS3
      function only when simultaneously expressed in a delta cys-3 strain. In addition,
      constructs having the CYS3 leucine zipper swapped for that of the oncoprotein Jun
      or the CYS3 leucine zipper extended by a heptad repeat showed wild-type CYS3
      function when transformed into a delta cys-3 strain. Gel mobility shift and
      immunoprecipitation assays were used to confirm the modified CYS3 proteins
      dimerization and DNA binding properties. The studies, which precluded wild-type
      CYS3 dimerization, indicate that in vivo CYS3 is fully functional as a homodimer
      since no interaction was required with other leucine zipper proteins to activate
      sulfur regulatory and structural gene expression. The results demonstrate the
      utility of leucine zipper modification to study the in vivo function of bZIP
      proteins.

PMID- 7731793
TI  - Hairpin properties of single-stranded DNA containing a GC-rich triplet repeat:
      (CTG)15.
AB  - Although triplet repeat DNA sequences are scattered throughout the human genome,
      their biological function remains obscure. To aid in correlating potential
      structures of these nucleic acids with their function, we propose their
      classification based on the presence or absence of a palindromic dinucleotide
      within the triplet, the G + C content, and the presence or absence of a
      homopolymer. Five classes of double-stranded (ds) triplet repeats are
      distinguished. Class I repeats, which are defined by the presence of a GC or CG
      palindrome, have the lowest base stacking energies, exhibit the lowest rates of
      slippage synthesis [Schlotterer and Tautz (1992) Nucleic Acids Res., 20, 211] and
      are uniquely associated with triplet repeat expansion diseases. The six single
      stranded (ss) triplet repeats within Class I also have the potential to form
      hairpin structures, as determined by energy minimization. To explore the
      possibility of hairpin formation by ss Class I triplet repeats, studies were
      performed with a ss oligonucleotide containing 15 prototypic CTG repeats [ss
      (CTG)15]. Electrophoretic, P1 nuclease and KMnO4 oxidation data demonstrate that
      ss (CTG)15 forms a hairpin containing base paired and/or stacked thymines in the
      stem. Potential functions of hairpins containing Class I triplet repeats are
      discussed with respect to protein translation and mRNA splicing. Further,
      potential roles of hairpin structures in triplet repeat expansion events are
      discussed.

PMID- 7731794
TI  - Coding sequence composition flanking either signal element alters V(D)J
      recombination efficiency.
AB  - Lymphoid V(D)J rearrangement is targeted by recombination signal sequences (RSS)
      bordering V, D or J exons. We demonstrate that the DNA composition of flanking
      coding positions, particularly poly(A) or poly(T) stretches at one or both RSS,
      diminishes V(D)J recombination up to 100-fold. Positionally correct cleavages
      occur in the inhibited reactions, since the junctions formed show the same
      frequency of precision as uninhibited reactions. Open/shut cleavage/rejoining is
      not increased at a normal RSS in substrates containing inhibitory A/T
      homopolymers versus random sequence at a second RSS. Thus recombinase action at
      both cleavage sites is severely disrupted by modified coding sequences.

PMID- 7731796
TI  - PCR with detachable primers.

PMID- 7731795
TI  - Deposition of histone H1 onto reconstituted nucleosome arrays inhibits both
      initiation and elongation of transcripts by T7 RNA polymerase.
AB  - The effect of histone H1 on transcription by bacteriophage T7 RNA polymerase was
      examined using reconstituted chromatin templates. A 3.8 kb linear DNA template
      consisting of a specific transcription promoter for T7 RNA polymerase placed
      upstream of 18 tandem repeats of a 207 bp nucleosome positioning sequence derived
      from the 5S rRNA gene of Lytechinus variegatus was used as a template for
      chromatin reconstitution. Regularly spaced arrays of nucleosome cores were
      assembled onto this DNA template from donor histone octamers by salt step
      dialysis. Histone H1 was incorporated onto free DNA or reconstituted chromatin
      templates and double label transcription assays were performed. The experiments
      indicated that histone H1 has a strong inhibitory effect on both transcription
      initiation and elongation. These effects are especially pronounced on chromatin
      templates, where both transcription initiation and elongation are virtually
      halted. The inhibition of transcription elongation appears to result from a
      dramatic increase in premature termination of transcripts. These experiments
      indicate that assembly of histone H1 into chromatin can result in structures
      which are completely repressed with respect to transcription.

PMID- 7731797
TI  - A method for screening arrayed cosmid libraries with mega insert yeast artificial
      chromosomes.

PMID- 7731798
TI  - An improved PCR method for walking in uncloned genomic DNA.

PMID- 7731799
TI  - An improved ligase-free method for directional subcloning of PCR amplified DNA.

PMID- 7731800
TI  - Transferring the purine 2-amino group from guanines to adenines in DNA changes
      the sequence-specific binding of antibiotics.
AB  - The proposition that the 2-amino group of guanine plays a critical role in
      determining how antibiotics recognise their binding sites in DNA has been tested
      by relocating it, using tyrT DNA derivative molecules substituted with inosine
      plus 2,6-diaminopurine (DAP). Irrespective of their mode of interaction with DNA,
      such GC-specific antibiotics as actinomycin, echinomycin, mithramycin and
      chromomycin find new binding sites associated with DAP-containing sequences and
      are excluded from former canonical sites containing I.C base pairs. The converse
      is found to be the case for a group of normally AT-selective ligands which bind
      in the minor groove of the helix, such as netropsin: their preferred sites become
      shifted to IC-rich clusters. Thus the binding sites of all these antibiotics
      strictly follow the placement of the purine 2-amino group, which accordingly must
      serve as both a positive and negative effector. The footprinting profile of the
      'threading' intercalator nogalamycin is potentiated in DAP plus inosine
      substituted DNA but otherwise remains much the same as seen with natural DNA. The
      interaction of echinomycin with sites containing the TpDAP step in doubly
      substituted DNA appears much stronger than its interaction with CpG-containing
      sites in natural DNA.

PMID- 7731801
TI  - A new approach to the synthesis of the 5'-deoxy-5'-methylphosphonate linked
      thymidine oligonucleotide analogues.
AB  - A new synthetic method for the preparation of the 5'-deoxy-5'-methylphosphonate
      linked thymidine oligonucleotides (5'-methylenephosphonate analogues) was
      developed. The method is based on the use of a phosphonate protecting group, 4
      methoxy-1-oxido-2-picolyl, enabling intramolecular nucleophilic catalysis which
      together with the condensing agent, 2,4,6-triisopropylbenzenesulfonyl chloride,
      secures fast and efficient formation of the 5'-methylenephosphonate
      internucleosidic bonds. The produced protected oligomers were treated with
      thiophenol and triethylamine to remove the phosphonate protecting groups, cleaved
      from the solid support using concentrated aqueous ammonia, and purified by HPLC.
      Several thymidine oligonucleotide analogues with the chain length of up to 20
      nucleotidic units, in which all internal 5'-oxygen atoms have been replaced by
      methylene groups directly bound to phosphorus, were synthesised using this
      methodology.

PMID- 7731802
TI  - CpG methylation has differential effects on the binding of YY1 and ETS proteins
      to the bi-directional promoter of the Surf-1 and Surf-2 genes.
AB  - The divergently transcribed Surf-1 and Surf-2 housekeeping genes are separated by
      a bi-directional, TATA-less promoter which lies within a CpG-rich island. Here we
      show that CpG methylation severely reduces transcription in the direction of both
      Surf-1 and Surf-2. Previous work has identified three promoter elements (Su1, Su2
      and Su3) which are conserved between the human and mouse Surf-1/Surf-2 promoters.
      These elements bind transcription factors present in human and mouse cell nuclear
      extracts in vitro and mutations which prevent factor binding also reduce promoter
      activity in vivo. Transcription initiation factor YY1 binds to the Su1 site and
      stimulates transcription in the direction of Surf-1 and, to a lesser extent, Surf
      2. Here we show that members of the ETS family of transcription factors bind to
      the Su2 site. Although the Su1 factor binding site contains three CpG
      dinucleotides, the binding of YY1 is not affected by CpG methylation. In
      contrast, CpG methylation abolishes the binding of ETS proteins to the Su2 site;
      methylation of a single cytosine, at position 3 of the consensus ETS site, is
      sufficient to prevent factor binding. This direct effect on the binding of ETS
      proteins is, however, not in itself sufficient to explain the repression of this
      promoter by CpG methylation. A mutation of the Su2 site which removes the
      sequence CpG, but which does not prevent ETS factor binding, fails to relieve
      this promoter from repression by CpG methylation.

PMID- 7731803
TI  - Determination of the origin cleavage and joining domain of geminivirus Rep
      proteins.
AB  - Replication of the single-stranded DNA genome of plant geminiviruses follows a
      rolling circle mechanism. It strictly depends on a 'rolling circle replication
      initiator protein', the M(r) 41 kDa viral Rep protein, encoded by the C1 or AC1
      genes. Using wheat dwarf virus (WDV) and tomato yellow leaf curl virus (TYLCV) as
      examples, we show that not only the full-size Rep proteins, but also a putative
      30 kDa translation product of WDV open reading frame C1-N as well as an
      artificially shortened 24 kDa Rep of TYLCV, cleave and join single-stranded
      origin DNA in vitro. Thus the pivotal origin recognition and processing
      activities of geminivirus Rep proteins must be mediated by the amino-terminal
      domain of Rep.

PMID- 7731804
TI  - Functional selection for the centromere DNA from yeast chromosome VIII.
AB  - Centromeres are essential components of eucaryotic chromosomes. In budding yeast,
      up to now, 15 of the 16 centromere DNAs have been isolated. Here we report the
      functional isolation and characterization of CEN8, the last of the yeast
      centromeres missing. The centromere consensus sequence for the 16 chromosomes in
      this organism is presented.

PMID- 7731805
TI  - Functional interactions between YY1 and adenovirus E1A.
AB  - YY1 is a C2H2-type zinc finger transcription factor that is a member of the human
      GLl-Kruppel family of proteins. YY1 represses transcription when bound upstream
      of transcription initiation sites. The repression can be relieved by adenovirus
      E1A and activation of target genes occurs. We have mapped the repression domain
      of YY1 to the C-terminal region, overlapping its DNA binding domain. We have also
      identified an activation domain within the first 69 amino acids of YY1. The YY1 C
      terminal region is involved in physical interactions with E1A and is functionally
      necessary for YY1 to respond to E1A. This suggests that relief of YY1 repression
      by E1A involves YY1-E1A physical interactions. Although not involved in
      interactions with E1A, the N-terminal activation domain is also necessary for YY1
      to respond to E1A. Presumably, under repressing conditions, the activation domain
      is masked by the conformation of YY1, but is released upon binding of E1A and is
      required to subsequently activate transcription. Consistent with this hypothesis,
      an ATF-2-YY1 chimeric protein containing the activation domain of ATF-2 and the C
      terminal two-thirds of YY1 is still a potent repressor. Unlike the mutant YY1
      lacking its own N-terminal activation domain, the chimeric protein is fully
      responsive to E1A.

PMID- 7731806
TI  - The Escherichia coli ribosomal RNA leader nut region interacts specifically with
      mature 16S RNA.
AB  - All ribosomal RNAs are preceded by leader sequences not present in the final
      ribosome particles. The highly conserved leader sequences of bacterial rRNAs are
      known to be important for the folding and assembly of functional ribosomes. Very
      likely transient binding of the leader to mature parts of the 16S RNA occurs
      during transcription. To better understand the mechanistic details of these
      functions we have performed a secondary structural analysis of E. coli ribosomal
      RNA leader transcripts by chemical modification and enzymatic hydrolysis studies.
      The data were combined with results from thermodynamic stability calculations to
      yield a generalized structural model. The same secondary structure of the leader
      core, comprising the nut-like sequences up to the mature 5' end of the 16S RNA,
      was deduced, irrespective if transcripts started at promoter P1 or 120
      nucleotides downstream at P2. Employing gelshift and cross-linking studies we
      were able to demonstrate that a part of the leader core, namely the nut-like
      sequence elements bind directly to specific regions within the mature 16S RNA.
      The sites of RNA-RNA cross-linking could be localized by sequencing. They map in
      the 16S RNA 5' domain at nucleotide positions G27 to G42, C48, G68, G117 and
      G126. The results may explain the recently observed scaffolding function of the
      leader RNA during ribosome biogenesis.

PMID- 7731807
TI  - Evidence for the requirement of protein synthesis and protein kinase activity in
      the temperature regulated stability of a Tetrahymena surface protein mRNA.
AB  - In Tetrahymena thermophila, the expression of the temperature-specific surface
      protein SerH3 is controlled primarily by a temperature-dependent change in the
      stability of its mRNA. The change in SerH3 mRNA stability occurs very rapidly
      after a shift in incubation temperature. This change in temperature could affect
      SerH3 mRNA stability directly by producing structural changes in the mRNA or
      regulatory factors acting on SerH3 mRNA. Alternatively, the temperature change
      could act indirectly through a signal transduction pathway leading to de novo
      synthesis of new regulatory factors or modifications of existing regulatory
      factors. To address these issues, we monitored the effect of temperature on an in
      vitro SerH3 mRNA decay assay and the in vivo effects of a variety of inhibitors
      against protein synthesis and protein kinases on SerH3 mRNA stability. The
      results of Northern analysis of SerH3 mRNAs in an in vitro mRNA decay assay
      indicate that temperature alone can not change the half-life of this mRNA.
      Furthermore, slot blot analysis of cytoplasmic RNAs show that protein synthesis
      and the action of protein kinases are not required for SerH3 mRNA turnover in
      cells grown at 30 degrees C. In contrast, our results indicate that the rapid
      decay of the SerH3 mRNA in cells grown at 30 degrees C and shifted to 40 degrees
      C requires a one time serine/threonine phosphorylation event which occurs at the
      temperature shift. In addition, the data show that a regulatory protein involved
      in rapid SerH3 mRNA decay must be newly and continuously synthesized following
      the temperature shift from 30 to 40 degrees C. These data show the complexity of
      temperature regulated mRNA decay and indicate that phosphorylation and protein
      synthesis are major factors in this process.

PMID- 7731808
TI  - Linkage isomerization reaction of intrastrand cross-links in trans
      diamminedichloroplatinum(II)-modified single-stranded oligonucleotides.
AB  - The stability of trans-(Pt(NH3)2[d(CGAG)-N7-G,N7-G]) adducts, resulting from
      cross-links between two guanine residues at d(CGAG) sites within single-stranded
      oligonucleotides by trans-diamminedichloro-platinum(II), has been studied under
      various conditions of temperature, salt and pH. The trans-(Pt(NH3)2[d(C GAG)-N7
      G,N7-G]) cross-links rearrange into trans-(Pt(NH3)2[d(CGAG)-N3-C,N7-G]) cross
      links. The rate of rearrangement is independent of pH, in the range 5-9, and of
      the nature and concentration of the salt (NaCl or NaCIO4) in the range 10-400 mM.
      The reaction rate depends upon temperature, the t1/2 values for the disappearance
      of the (G,G) intrastrand cross-link ranging from 120 h at 30 degrees C to 70 min
      at 80 degrees C. The linkage isomerization reaction occurs in oligonucleotides as
      short as the platinated tetramer d(CGAG). Replacement of the intervening residue
      A by T has no major effect on the reaction. The C residue adjacent to the adduct
      on the 5' side plays a key-role in the reaction; its replacement by a G, A or T
      residue prevents the reaction occuring. No rearrangement was observed with the C
      residue adjacent to the adduct on the 3' side. It is proposed that the linkage
      isomerization reaction results from a direct attack of the base residue on the
      platinum(II) square complex.

PMID- 7731809
TI  - Single base discrimination for ribonuclease H-dependent antisense effects within
      intact human leukaemia cells.
AB  - We have previously demonstrated, in vitro, that phosphodiester and
      phosphorothioate antisense oligodeoxynucleotides could direct ribonuclease H to
      cleave non-target RNA sites and that chimeric
      methylphosphonodiester/phosphodiester analogue structures were substantially more
      specific. In this report we show that such chimeric molecules can promote point
      mutation-specific scission of target mRNA by both Escherichia coli and human
      RNases H in vitro. Intact human leukaemia cells 'biochemically microinjected'
      with antisense effectors demonstrated efficient suppression of target mRNA
      expression. It was noted that the chimeric methylphosphonodiester/phosphodiester
      structures showed single base discrimination, whereas neither the phosphodiester
      nor phosphorothioate compounds were as stringent. Finally, we show that the
      antisense effects obtained in intact cells were due to endogenous RNase H
      activity.

PMID- 7731810
TI  - Late induction of human DNA ligase I after UV-C irradiation.
AB  - We have studied the regulation of DNA ligase I gene expression in UV-C irradiated
      human primary fibroblasts. An increase of approximately 6-fold both in DNA ligase
      I messenger and activity levels was observed 24 h after UV treatment, when
      nucleotide excision repair (NER) is no longer operating. DNA ligase I induction
      is serum-independent and is controlled mainly by the steady-state level of its
      mRNA. The activation is a function of the UV dose and occurs at lower doses in
      cells showing UV hypersensitivity. No increase in replicative DNA polymerase
      alpha activity was found, indicating that UV induction of DNA ligase I occurs
      through a pathway that differs from the one causing activation of the replication
      machinery. These data suggest that DNA ligase I induction could be linked to the
      repair of DNA damage not removed by NER.

PMID- 7731811
TI  - S-adenosyl methionine alters the DNA contacts of the EcoKI methyltransferase.
AB  - The EcoKI methyltransferase methylates two adenines on opposite strands of its
      bipartite DNA recognition sequence AAC(N6)GTGC. The enzyme has a strong
      preference for hemimethylated DNA substrates, but the methylation state of the
      DNA does not influence its binding affinity. Methylation interference was used to
      compare the contacts made by the EcoKI methyltransferase with unmodified,
      hemimethylated or fully modified DNAs. Contacts were seen at or near the N7
      position of guanine, in the major groove, for all of the guanines in the EcoKI
      recognition sequence, and at two guanines on the edge of the intervening spacer
      sequence. The presence of the cofactor and methyl donor S-adenosyl methionine had
      a striking effect on the interference pattern for unmodified DNA which could not
      be mimicked by the presence of the cofactor analogue S-adenosyl homocysteine. In
      contrast, S-adenosyl methionine had no effect on the interference patterns for
      either kind of hemimethylated DNA, or for fully modified DNA. Differences between
      the interference patterns for the unmodified DNA and any of the three forms of
      methylated DNA provide evidence that methylation of the target sequence
      influences the conformation of the protein-DNA interface, and illustrate the
      importance of S-adenosyl methionine in the distinction between unmodified and
      methylated DNA by the methyltransferase.

PMID- 7731812
TI  - Identification of 3' alpha-hs4, a novel Ig heavy chain enhancer element regulated
      at multiple stages of B cell differentiation.
AB  - In addition to E mu, several elements downstream of the IgH cluster, i.e. 3' of
      the C alpha gene, are involved in regulating IgH gene rearrangement and
      expression. This entire downstream regulatory region was shown to be deleted in
      the mutant myeloma cell line, LP1.2. The deletion encompasses approximately 34 kb
      and is presumably responsible for the reduced levels of IgH expression in this
      cell line. An additional regulatory element, included in the LP1.2 deletion, was
      identified by investigation of a DNase I hypersensitivity site located
      approximately 33 kb downstream of the alpha gene and present in pre-B and plasma
      cells. This novel IgH gene enhancer element, termed 3' alpha-hs4, is capable of
      activity throughout B cell development. Transient transfection of 3' alpha-hs4 in
      a CAT reporter gene construct shows transcriptional enhancement activity
      approximating that of E mu in S194 plasmacytoma and M12.4.1 and A-20 B cell
      lines; while in a pre-B cell line, 18-81, the average activity is 25% that of E
      mu. Enhancer activity was localized to an 800 bp fragment. The activity of 3'
      alpha-hs4 is orientation independent and appears to be B cell specific. Tight
      regulation of 3' alpha-hs4 is inferred from its variable activity in different
      plasmacytoma cell lines and within the pre B cell line, 18-81.

PMID- 7731813
TI  - High-throughput DNA synthesis in a multichannel format.
AB  - We describe an approach to high-throughput parallel DNA synthesis in which a
      multiwell format is used. The reactions are carried out in open wells using an
      argon ambient atmosphere to prevent reagent contamination. The controlled-pore
      glass beads which form the substrate for synthesis are held in individual wells
      with high-density polyethylene filter bottoms through which reagents are drawn
      into a vacuum manifold. The synthesis is carried out using direct reagent
      dispensing into the individual reaction wells. A computer controls the sequence
      in which reagents are dispensed and the timing of the periodic vacuum pulses
      required to synthesize the desired sequence. Experiments to date have
      demonstrated the viability of the approach for a variety of test sequences.
      Results obtained with HPLC analysis demonstrate coupling efficiencies as high as
      99.5% under optimized conditions. Use of the oligomers for DNA sequencing
      templates and as PCR primers has been demonstrated in production applications.
      The current instrument design consists of a series of discrete reaction chambers
      in a 12 channel module which can be multiplexed in a 12 x n format where n can be
      1-8, i.e. 96 wells. A projected time interval for 12 parallel syntheses is 2.5 h,
      with 96 syntheses in 3.5 h. Because of the reduced volume of reagents required in
      the open well format, significant cost savings are projected.

PMID- 7731814
TI  - In vitro transcription close to the melting point of DNA: analysis of Thermotoga
      maritima RNA polymerase-promoter complexes at 75 degrees C using chemical probes.
AB  - The interaction of DNA dependent RNA polymerase of the extreme thermophile
      bacteria Thermotoga maritima with a promoter bearing DNA fragment was
      investigated in the temperature range from 20 to 85 degrees C. We show that the
      T. maritima RNA polymerase recognizes and utilizes the Escherichia coli T7 A1
      promoter with an efficiency similar to that of the E. coli polymerase. We have
      investigated the interaction of both polymerases with the same promoter over a
      wide range of temperatures using hydroxyl radical foot-printing and osmium
      tetroxide probing. This study revealed that the T. maritima polymerase goes
      through a series of isomerisation events very similar to the E. coli polymerase,
      i.e. the closed, intermediate and open complexes, but the transitions themselves
      occur at radically different temperatures. This indicates that conformational
      changes in the DNA that accompany initiation of transcription such as promoter
      melting are determined by the polymerase rather than the DNA sequence.

PMID- 7731816
TI  - Professional development. Blood pressure: knowledge for practice (continuing
      education credit).

PMID- 7731815
TI  - Protein binding interactions at the STB locus of the yeast 2 microns plasmid.
AB  - The cis-acting STB locus has been shown to be a multiple protein binding site.
      STB-specific binding activity was detected in a normally insoluble yeast cell
      protein fraction, suggesting association with a subcellular structure. Both 2
      microns-encoded and host-encoded STB-binding activities were identified. The 2
      microns proteins showed contrasting STB-binding activities: C (REP2) protein
      acted cooperatively with the host factor to promote STB binding; B (REP1) protein
      also acted in association with the host factor, but showed a dual action,
      opposing or facilitating binding, depending upon concentration; D (RAF) exhibited
      rapid binding and antagonism to host factor binding. FLP did not bind, but
      promoted host factor dissociation. The implications of these activities for the
      molecular mechanism of 2 microns plasmid inheritance are considered.

PMID- 7731817
TI  - Critical condition.

PMID- 7731818
TI  - Relative lives.

PMID- 7731819
TI  - Talking back to happiness. Interview by John Illman.

PMID- 7731820
TI  - Pay campaign. Body negative.

PMID- 7731821
TI  - Extending professional practice: benefits and pitfalls.
AB  - This article highlights the changing role of the nurse in the A&E department. It
      discusses the arguments for and against nurses taking on more medical tasks and
      some of the legal and professional issues this inevitably raises. Particular
      reference is made to the Scope of Professional Practice, Code of Professional
      Conduct and Exercising Accountability documents produced by the UKCC. The
      conclusion from the literature is that although the term 'extended role' is no
      longer acceptable, there are no guidelines as to how adjustments to practice are
      to be monitored. The documents issued by the UKCC do not say how the practitioner
      is to prove that he or she has undergone any kind of training in order to perform
      these extra tasks. As a result, it is imperative that the practitioner is aware
      of the professional issues involved in order to safeguard both the patient and
      practitioner and to ensure safe standards of practice.

PMID- 7731822
TI  - The evolution of practice.
AB  - This paper describes the development, role and functions of a nursing clinical
      practice group. In the first section, the transition of the clinical practice
      group from a low-key, management-led and reactive group, to one which is
      clinically led, high-profile and proactive, influencing and shaping nursing
      decisions within the unit in which it operates is described. In the second, the
      focus is on the approach of the clinical practice group to issues surrounding the
      Scope of Professional Practice using this to illustrate the group's proactive
      nature and its potential for bringing about and supporting change in practice.

PMID- 7731823
TI  - Making sense of ... clinical features of inflammation.
AB  - Although often associated with abnormal pathological processes, inflammation is a
      normal physiological response. This paper defines inflammation, looks briefly at
      the physiological processes involved and discusses implications for nursing.

PMID- 7731824
TI  - Who should examine the 'normal' neonate?
AB  - Newborn babies are examined twice in the maternity unit, once by a midwife and
      once by a doctor, or if born at home, by the GP. In this paper, the author
      assesses the value of the examination carried out on the newborn and asks who is
      the most appropriate health practitioner to carry it out. If midwives are to
      become the lead professional in examining the newborn, they must be willing to
      take responsibility if defects are missed, the author argues.

PMID- 7731825
TI  - Educational developments for the practice nurse specialty.
AB  - A number of constraints have hitherto prevented practice nurses from meeting
      their learning needs. In this paper the author outlines the new educational
      opportunities coming on stream in the wake of the UKCC PREP initiative. The need
      for a range of educational programmes is stressed and the key elements of a
      diploma course for practice nurses in north London are also explained.

PMID- 7731826
TI  - Unlocking the doors.

PMID- 7731827
TI  - Who were ... Cheyne and Stokes?

PMID- 7731828
TI  - Fit for care.

PMID- 7731829
TI  - Complementary medicine. The uncharted mind.

PMID- 7731830
TI  - Treating hayfever: over-the-counter remedies.

PMID- 7731831
TI  - Plus ca change.

PMID- 7731833
TI  - Professional development. Blood pressure: the role of the nurse (continuing
      education credit).

PMID- 7731832
TI  - HIV specialist is new head at RCN Glasgow.

PMID- 7731834
TI  - A child found to be HIV positive shortly after birth appears now to be clear of
      the infection.

PMID- 7731835
TI  - Shadows of death.

PMID- 7731836
TI  - Pay campaign. Working to rules.

PMID- 7731837
TI  - Closing options.

PMID- 7731838
TI  - Pre-admission clinics for thoracic surgery.

PMID- 7731839
TI  - Evaluating pre-operative care.
AB  - Accounts of the establishment of a pre-operative assessment clinic (PAC) and the
      benefits to patients have been well documented. These initiatives have been in
      response to the Patient's Charter, the Health of the Nation, and an increase in
      patients' expectation of the service provided. The development of the PAC in
      orthopaedics within our unit originated through the insight of one consultant who
      had seen the benefits of this type of clinic before, while working in Canada.
      This paper describes the evaluation of our work.

PMID- 7731840
TI  - Systems of life. Endocrine system: an overview.

PMID- 7731841
TI  - Attitude of prison nurse officers to drug misusers.
AB  - The key group involved in delivering health care to drug misusers in prison is
      the prison nurse officers. The literature suggests that the skills and knowledge
      base of this professional group has received very little attention. This study
      looked at the attitudes of prison nurse officers in Scotland towards intravenous
      drug misusers. Age, sex and grade appeared to affect attitudes, but the results
      were not clear cut. Some stereotyping of drug misusers was evident among
      respondents. Drug misusers are a marginalised group in terms of health care and
      it is important that their needs are addressed in prison. Prison nurse officers
      should be proactive in meeting such needs, and should be given adequate support
      to do so. This paper suggests that the skills of such staff are often not being
      used appropriately.

PMID- 7731842
TI  - Monitoring environmental hazards in the workplace.
AB  - This paper, the fifth in a series, looks at the importance of monitoring the
      environment. A number of case studies are used to illustrate specific points.

PMID- 7731843
TI  - Losing control.

PMID- 7731844
TI  - The twilight zone.

PMID- 7731845
TI  - Student supplement. Time to stand up and fight.

PMID- 7731846
TI  - Student supplement. Learning to care. Interview by Jane Seymour.

PMID- 7731848
TI  - Professional development. Blood pressure: revision notes (continuing education
      credit).

PMID- 7731847
TI  - Student supplement. Charting a course.

PMID- 7731849
TI  - Last of the boat people. Interview by Lynn Eaton.

PMID- 7731850
TI  - Pay campaign. Stringing along.

PMID- 7731851
TI  - Warned in the USA.

PMID- 7731852
TI  - Acute pain: its physiology and the pharmacology of analgesia.
AB  - Although viewed as a common occurrence, post-operative pain continues to generate
      episodes of poor care. It has been suggested that more than 50% of patients have
      pain for most of the 72 hours after surgery. Within pain management, the
      importance of psychological and social influences are widely accepted, but it is
      important to have an understanding of the physiology of pain. Yet historically
      nurses have often been seen to have had a poor understanding of opioids, leading
      to inadequate administration of these drugs. Few would argue against the
      suggestion that recent advances in pain management have improved patient care,
      but nurses need to be fully aware of the basic foundations of the physiology of
      pain and pain management if patient care in this area is to continue to improve.

PMID- 7731853
TI  - Pain from sickle-cell crisis.
AB  - A qualitative questionnaire survey was carried out to identify the perceptions
      and expectations of pain management of patients with sickle-cell disease, and of
      nurses. The study illustrates that the present sample of nurses contributed to
      the poor pain control of sickle-cell patients because of their misconceptions
      about narcotic addiction, inadequate formal pain assessment and their neglect of
      attention to the psychosocial implications of this chronic disease.

PMID- 7731854
TI  - Ecstasy (MDMA): alerting users to the dangers.
AB  - In this paper, the author outlines the chemical make-up of the recreational drug
      ecstasy, and describes signs and symptoms of intoxication which are especially
      useful to A&E nurses. He describes the effects of the drug on the users, and
      suggests advice which should be given to users on admission.

PMID- 7731855
TI  - Microbiological examination of blood for septicaemia.
AB  - The immune defences of blood are normally sufficient to protect against infection
      by the few bacteria that occasionally find their way into the peripheral
      circulation. When these host defence mechanisms are overwhelmed, uncontrolled
      bacterial infection of the blood (septicaemia) develops. Septicaemia is a
      potentially life-threatening clinical emergency that demands urgent diagnosis and
      treatment. This paper describes some aspects of septicaemia and the way in which
      the microbiology laboratory contributes to the care of patients suspected of
      having septicaemia.

PMID- 7731856
TI  - Measuring the quality of service in the community.
AB  - This paper describes a joint project carried out by clinical psychologists and
      senior trusts managers to identify and measure consumer outcomes across a range
      of community services. The outcomes identified have been written into service
      contracts, and the outcome data are collected on a regular basis and used to
      inform management decisions.

PMID- 7731857
TI  - Setting a new course.

PMID- 7731858
TI  - Learning capers.

PMID- 7731859
TI  - Complementary medicine. Back to the balance sheet.

PMID- 7731860
TI  - Joint venture.

PMID- 7731861
TI  - First line of defence.

PMID- 7731863
TI  - Continence. Strategic renewal.

PMID- 7731862
TI  - Continence. Value for money.

PMID- 7731864
TI  - Continence. Systems for leg bags.

PMID- 7731865
TI  - Breast feeding practices among rural mothers of Delhi.

PMID- 7731866
TI  - Nursing scene in Uttar Pradesh: a report.

PMID- 7731867
TI  - Labour room practices conducive to breast-feeding.

PMID- 7731868
TI  - An interview with nursing advisor to govt. of India.

PMID- 7731870
TI  - Geriatrics today and tomorrow.

PMID- 7731869
TI  - Health for all by 2000 AD: the role of Ayurveda.

PMID- 7731871
TI  - Nursing scene in Uttar Pradesh--a report.

PMID- 7731872
TI  - Wenckebach upper rate response of dual chamber pacemakers: a reappraisal and
      proposed new terminology.

PMID- 7731873
TI  - Predictors of defibrillation energy requirements with nonepicardial lead systems.
AB  - The determinants of high defibrillation energy requirements (DER) using
      nonepicardial lead systems (NELS) have not been well characterized. The goal of
      this study was to examine prospectively the influence of clinical, radiographic,
      echocardiographic, and procedural variables on DER during NELS placement. Data
      from 100 consecutive patients undergoing attempted NELS implantation were
      analyzed. Transvenous leads, subcutaneous patches, and monophasic shock devices
      from two manufacturers were used. Leads were successfully positioned for testing
      in 95% of patients. An adequate DER (< or = 25 J) was obtained in 73 of 95 (77%)
      of patients. Univariate analysis identified amiodarone therapy and left
      ventricular mass as predictors of high DER. With multivariate analysis,
      amiodarone therapy was the sole significant predictor of high DER (P = 0.002,
      odds ratio 5.46). The 22 patients with high NELS DER also had high epicardial DER
      (mean 24 +/- 9 J). The two patch epicardial DER was > 25 joules in 12 of 22
      patients. Thus, adequate DER with monophasic shock waveforms can be obtained in
      most patients undergoing NELS testing. However, amiodarone therapy significantly
      increases the probability of obtaining high DER.

PMID- 7731874
TI  - Frequency analysis of the P wave: comparative techniques.
AB  - Frequency domain analysis of the signal-averaged P wave (SAPW) may provide
      additional information over time domain analysis in patients with paroxysmal
      atrial fibrillation (PAF), but an optimum method has not yet been defined. We
      compared two different approaches using SAPW and test signals. We analyzed the
      frequency spectrum of the entire P wave (method A) or of only its terminal 100
      msec (method B) using SAPW from 24 patients with idiopathic PAF and 34 normal
      controls. Absolute powers in frequency bands above 20, 30, 40, 60, and 80Hz (P20,
      P30, P40, P60, and P80) and power ratios about these frequencies (PR20, PR30,
      PR40, PR60, and PR80) were calculated. Patients had greater P30, P60, and P80
      using method A (P30: 28.6 [+/- 2.2] vs 22.8 [+/- 1.6] microV2.s; P = 0.04; P60:
      4.7 [+/- 0.5] vs 3.4 [+/- 0.3] microV2.s; P = 0.03; P80: 1.9 [+/- 0.2] vs 1.3 [+/
      0.09] microV2.s; P = 0.01) but differences were smaller with method B. Moving
      the P wave endpoint 10 msec into the P wave had no effect on frequency domain
      parameters using method A but produced important changes using method B. Both
      methods were also applied to test signals of different durations but equal powers
      and power ratios. Method A gave predicted values for power and PR40 at all signal
      durations, but method B produced variable results. Frequency domain analysis of
      the SAPW shows significant increases in P wave energy in patients with PAF
      compared to controls. Analysis of the entire P wave is influenced less by signal
      duration and variations of the P wave endpoint than analysis of the terminal P
      wave alone and may define patient and control populations more precisely.

PMID- 7731875
TI  - Long-term follow-up of pacemaker lead systems: establishment of standards of
      quality.
AB  - The functional details of all 5,405 pacemaker leads implanted on Montefiore
      Medical Center were contemporaneously recorded between 1960 and May 31, 1993.
      Some models have been observed for as long as 24 years. Ventricular leads with
      more than 50 and atrial leads with more than 30 implanted units have been
      continually and repeatedly subjected to actuarial cumulative survival rate (CSR)
      analysis during which clinical decisions, such as continued lead implantation,
      cessation of use, or early withdrawal from service, were made. CSR evaluation for
      many lead models by the Mantel-Haenszel method allowed comparison of the
      performance of contemporaneous lead models with older and new technologies. No
      effect on lead longevity, durability, on mode of end of lead service, lead
      removal independent of function (e.g., for infection), materials, or
      physiological failure was found due to an operator or anatomical route of venous
      access. Multifilar silicone rubber insulated leads have longevity (CSR) superior
      to monofilar silicone rubber leads. The cumulative survival of silicone rubber
      insulated monofilar models 6901, 6907, continuous lead (CL), 4 mm, and 2 mm was
      79%-91%, 20 years after implantation. Multifilar silicone rubber insulated models
      6961 and 4116 had a cumulative survival of 99%-100%, 15 years after implantation.
      Among multifilar polyurethane insulated leads, distinct longevity differences
      exist between formulations and contemporaneous models that are normally similar,
      yielding a bimodal longevity distinction; model 6971 (ventricular) has 95% CSR
      and 6991U (atrial) has 94% CSR, 10 years after implantation. Both performed less
      well than other contemporaneous models, which approximate 100% CSR. The 10-year
      CSR for leads implanted between 1960-1975 (Era 1) is 98.7%, and the 10-year CSR
      of leads implanted between 1981-1985 (Era 3) is 99.4%. Comparison of individual
      lead models, and all leads of specific eras, allows development of survival
      expectations and standards of quality for comparison between contemporaneous lead
      models and different eras of manufacture. As the highest available lead CSR sets
      the standard, statistical deviation of a model from the best performance of a
      specific era should be considered as an indication of reduced quality.

PMID- 7731876
TI  - Radioisotopic pacemaker: long-term clinical results.
AB  - In order to prolong the service life of the generator, the isotopic pacemakers,
      powered by Pu238, have been developed and implanted since 1970. We report the
      follow-up of 325 patients (mean age 39 +/- 18 years) implanted with an isotopic
      pulse generator (Medtronic 9000/9090) between April 1970 and July 1982. The mean
      follow-up was 12 years (range 6 days to 18.5 years). The generator was highly
      reliable; the mean value of pacing rate between implantation and last follow-up
      decreased significantly but no more than 1 beat/min (72.7 vs 71.8 beats/min; P <
      0.001) and the pulse width did not change significantly. The actuarial survival
      of the device was 97% at 18.5 years. During the follow-up period, 122
      reoperations were performed in 85 patients: 88 explanations of the entire pacing
      system and 34 modifications of the lead system. Lead dysfunction accounted for
      68% of the 122 reoperations, generator failure for 6%, and miscellaneous reasons
      for 26%. However, 72% of patients remain free of intervention during the follow
      up period and 61 patients (20%) died during this period. Most deaths (52%) were
      of nonsudden cardiovascular origin, 17% were related to cancer, and 13% to sudden
      death. After 5, 10, and 18.5 years, 94%, 89%, and 73% of the patients were alive,
      respectively. No side effect could be attributed to the radioisotope. We conclude
      that this isotopic pacemaker demonstrated its reliability for long-term cardiac
      pacing.

PMID- 7731877
TI  - Inhibition of atrial electrical activity by ventricular pacing mediated by vagal
      stimulation.
AB  - In the absence of retrograde (VA) conduction, ventricular pacing does not exert
      any appreciable effect upon atrial electrical activity. We report three patients
      (2 with complete AV block and 1 with preserved AV conduction) in which, during EP
      study, no VA conduction was present and, in spite of that, excessive suppression
      (for more than 15 secs in the first patient) of sinus (atrial) electrical
      activity during RV pacing was observed. The sinus node suppression was
      reproducible in two patients. In all patients the suppression phenomenon was not
      observed after intravenous administration of atropine, which suggests that it was
      mediated by enhanced vagal tone.

PMID- 7731878
TI  - Adenosine-sensitive atrial tachycardia.
AB  - Limited data suggest that adenosine termination of atrial tachycardia is
      uncommon. To investigate further the effect of adenosine on atrial tachycardia,
      adenosine (6-12 mg) was administered during sustained atrial tachycardia in 17
      patients. All patients underwent electrophysiological study to exclude other
      mechanisms of supraventricular tachycardia. Mean patient age was 51 +/- 20 years
      (range 18-82 years). Seven patients had no structural heart disease. The mean
      atrial tachycardia cycle length was 390 +/- 80 msecs (range 260-580). Sustained
      atrial tachycardia was induced with atrial extrastimuli in 8 patients, and was
      either incessant at baseline or developed spontaneously during isoproterenol
      infusion in 9 patients. Adenosine terminated atrial tachycardia in 3 patients
      (18%), transiently suppressed atrial tachycardia in 4 patients (23%), and
      produced AV block without affecting tachycardia cycle length in the remaining 10
      patients. Adenosine sensitivity was observed in 3 of 8 patients with tachycardias
      initiated and terminated by atrial extrastimuli, and in 4 of 9 patients with
      spontaneous, but not inducible tachycardias including 3 of 4 patients with
      isoproterenol facilitated tachycardias. Of multiple clinical and
      electrophysiological variables examined as potential predictors of adenosine
      sensitivity, only isoproterenol facilitation of spontaneous or inducible
      sustained tachycardia predicted adenosine sensitivity (P = 0.02). These
      observations suggest that adenosine-sensitive atrial tachycardia may be more
      common than previously recognized. Adenosine sensitivity does not appear to be
      specific for tachycardia mechanism and cannot be predicted by response to pacing.
      Atrial tachycardias dependent on beta-adrenergic stimulation are most likely to
      be terminated by adenosine.

PMID- 7731879
TI  - Myocardial temperature response during radiofrequency catheter ablation.
AB  - During radiofrequency catheter ablation, steady-state electrode-tissue interface
      temperatures are reached within 5 seconds. Within the myocardium, however, a much
      slower temperature rise has been observed in vitro with stabilization after
      approximately 2 minutes. The discrepancy suggests that tissue temperature rise
      time depends on distance from the ablation electrode and, thus, that temperature
      rise measured at the electrode-tissue interface does not correspond with
      temperature rise within the myocardium. In five beagles, closed-chest
      radiofrequency catheter ablation was performed in the vicinity of intramural
      thermocouples. Sequences of 60 seconds, 10- and 25-watt pulses were delivered in
      the unipolar mode via the 4-mm distal electrode of a 7 French steerable catheter.
      At all distances > 3 mm from the ablation electrode, the rate of myocardial
      temperature rise was low: relative rise after 5, 10, 20, and 30 seconds was 22%,
      32%, 48%, and 63% of that achieved at 60 seconds, and even then steady-state
      temperatures had not yet been reached. Temperature rise was faster at sites
      closer to the ablation electrode. There was no difference in rate of rise between
      first and second pulses at the same site. A 6% higher myocardial temperature was
      reached with a second identical pulse at the same site. Tissue temperatures
      achieved with 25 watts were 2.4 times higher than with a preceding 10-watt pulse
      at the same ablation site.

PMID- 7731880
TI  - Programming of the pacing impulse in pacemakers connected to steroid lead
      systems.
AB  - The purpose of the study was to compare the feasibility of low amplitude output
      programming (2.5 V/0.5 msec) 3 or more months after pacemaker implantation in
      patients receiving steroid and nonsteroid lead systems. Chronic pacing voltage,
      current, and energy thresholds were determined from 0.05- to 1.0-msec pulse
      duration in 44 patients with steroid lead systems, and in 36 patients with
      nonsteroid lead systems; all patients received pacemakers from the same
      manufacturer, which utilized the same programming and telemetry features.
      Chronaxie, pulse duration at the lowest pacing current, and energy were assessed
      from individual threshold curves. Steroid-eluting leads had significantly lower
      pacing voltage, current, and energy thresholds than nonsteroid leads. A 100%
      safety threshold margin could be achieved in 43 (98%) patients with steroid lead
      systems and in 27 (75%; P < 0.05) patients with nonsteroid lead systems with
      output programming of 2.5 V/0.5 msec. Chronaxie (0.22 +/- 0.17 msec vs 0.44 +/-
      0.31 msec; P < 0.05), pulse duration at lowest pacing current (0.28 +/- 0.12 msec
      vs 0.49 +/- 0.22 msec; P < 0.05), and pulse duration at lowest pacing energy
      (0.31 +/- 0.17 msec vs 0.53 +/- 0.22 msec; P < 0.05) were significantly shorter
      for steroid than for nonsteroid lead systems. In 42 patients of the former group,
      a 100% safety margin could be maintained either with a 2.5 V/0.3 msec or with a
      1.6 V/0.5 msec output. Conclusions Low amplitude output programming can be
      obtained in almost all pacemakers connected to steroid-eluting lead systems, and
      in a significantly higher number of patients than when connected with nonsteroid
      leads systems.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731881
TI  - Cellular electrophysiological changes induced in vitro by radiofrequency current:
      comparison with electrical ablation.
AB  - The purpose of this study was to examine the cellular electrophysiological
      effects of radiofrequency energy delivery in an in vitro canine epicardial
      preparation and compare the effects of those of high energy electrical ablation
      in a similar preparation. Ten joules of direct current energy or 40 volts of
      radiofrequency energy were delivered by a 6 French 2-mm tip catheter to the
      epicardial surface of 2 x 3 cm epicardial strips superfused with Tyrode's
      solution. Direct current energy delivery produced a crater and central zone of
      necrosis surrounded by a border zone of viable but damaged tissue that extended
      up to 10-12 mm from the site of energy delivery. Cellular electrophysiological
      abnormalities that included a less negative resting membrane potential, decreased
      peak dV/dT, decreased action potential amplitude, and decreased action potential
      duration (APD) were approximately linearly related to the distance from the
      crater edge. In addition, viable and inexcitable cells were frequently
      interspersed. Between 2 and 5 mm from the crater edge, 36.4% of the cells were
      inexcitable whereas others displayed normal action potential characteristics. In
      contrast, radiofrequency current produced a central zone of necrosis surrounded
      by a smaller border zone. Cellular damage that was qualitatively similar to that
      produced by direct current energy extended only up to 6-8 mm from the edge of the
      crater. In addition, severe abnormalities were noted in intracellular potentials
      recorded within 2 mm of the ablation site, and only minor abnormalities further
      away. Lesions were relatively homogeneous. Between 2 and 5 mm from the ablation
      site only 2.6% of the cells were inexcitable (P < 0.05 vs direct current). In
      conclusion, radiofrequency current produces lesions that are smaller and more
      homogeneous than those produced by direct current ablation. Although the border
      zone is small, a region of partially depolarized but viable myocardium is present
      after radiofrequency current energy delivery. These findings provide a cellular
      basis for several clinical observations that have been made following
      radiofrequency current energy delivery.

PMID- 7731882
TI  - Ventricular tachycardias with left bundle branch block morphology.
AB  - The differential diagnosis of VTs with LBBB morphology includes several well
      defined syndromes. Although the majority of cases are attributable to acquired
      structural heart disease, including ischemia, prior infarction, or dilated
      cardiomyopathy, consideration of specific right ventricular processes is
      essential to proper evaluation and treatment. The approach to older patients or
      those with evidence for heart disease should begin with an evaluation for
      coronary artery disease and an assessment of biventricular function. Careful
      evaluation for bundle branch reentry should be performed during
      electrophysiological study, especially when there is underlying conduction system
      disease. Younger patients, those without overt heart disease, or those with
      isolated right ventricular disease, should receive a complete noninvasive
      evaluation of right and left ventricular size and function. An abnormal SAECG or
      identification of intracardiac late potentials suggest right ventricular
      dysplasia or cardiomyopathy, whereas responsiveness to adenosine and absence of
      detectable heart disease support the diagnosis of idiopathic right VT. Newer
      techniques, including MRI, show promise in identifying subtle right ventricular
      disease not otherwise detectable even in the setting of presumed idiopathic right
      VT. Following surgical repair of selected congenital heart defects, particularly
      tetralogy of Fallot, symptoms of recurrent palpitations, near syncope, syncope,
      or aborted sudden death may be attributable to recurrent VT, and diagnostic
      electrophysiological study should be considered for these patients. Finally, SVTs
      with LBBB morphology, particularly cases associated with right-sided or septal
      accessory pathways, should always be considered in this differential diagnosis.

PMID- 7731883
TI  - Computer files.
AB  - From what has been said, several recommendations can be made for users of small
      personal computers regardless of which operating system they use. If your
      computer has a large hard disk not specially required by any single application,
      organize the disk into a small number of volumes. You will then be using the
      computer as if it had several smaller disks, which will help you to create a
      logical file structure. The size of individual volumes has to be selected
      carefully with respect to the files kept in each volume. Otherwise, it may be
      that you will have too much space in one volume and not enough in another. In
      each volume, organize the structure of directories and subdirectories logically
      so that they correspond to the logic of your file content. Be aware of the fact
      that the directories suggested as default when installing new software are often
      not the optimum. For instance, it is better to put different graphics packages
      under a common subdirectory rather than to install them at the same level as all
      other packages including statistics, text processors, etc. Create a special
      directory for each task you use the computer. Note that it is a bad practice to
      keep many different and logically unsorted files in the root directory of any of
      your volumes. Only system and important service files should be kept there.
      Although any file may be written all over the disk, access to it will be faster
      if it is written over the minimum number of cylinders. From time to time, use
      special programs that reorganize your files in this way.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7731884
TI  - The dilemma of investigational and crossover therapies: continuing aftershocks of
      Federal probes.

PMID- 7731885
TI  - Electrophysiology rounds: a case of a hidden tachycardia.

PMID- 7731886
TI  - Late occurrence of incessant atrial tachycardia following the maze procedure.
AB  - We report a patient with incessant atrial tachycardia and AV nodal reentrant
      tachycardia tachycardia and AV nodal reentrant tachycardia beginning almost 18
      months following a successful maze procedure. Both tachycardias were cured by
      radiofrequency ablation. We speculate that the right atrial tachycardia may have
      been related to the maze procedure. Finally, we believe this report should
      emphasize the importance of careful and long-term follow-up of all patients
      undergoing the maze procedure. Proper evaluation of the place of this therapy
      greatly depends on reporting of all short- and long-term complications of this
      new procedure.

PMID- 7731887
TI  - P wave oversensing in a unipolar VVI pacemaker.
AB  - A 45-year-old male had a VVI pacemaker implanted 20 years ago because of complete
      heart block. Because of perforation of the lead the pulse generator was removed
      after 4 weeks and a second lead was implanted from the contralateral side.
      Recently, the patient presented with symptoms of lightheadedness and syncope
      associated with prolonged pauses in the electrocardiogram. From the ECG, the ECG
      interpretation channel, and intracardiac electrogram telemetry, it was concluded
      that the VVI pacemaker was inhibited by P waves. The most likely explanation for
      this phenomenon was an insulation defect in the functioning lead caused by
      friction with the abandoned lead at the level of the high right atrium.

PMID- 7731888
TI  - Reporting a single center's results with the Teletronics Accufix model of active
      fixation leads.

PMID- 7731889
TI  - Recall by Telectronics Pacing Systems of all unimplanted Accufix atrial "J"
      pacemaker leads, models 330-801.

PMID- 7731890
TI  - [Tests on the structure, function and urinary excretion of Tamm-Horsfall protein
      in urine].

PMID- 7731891
TI  - Excess cardiovascular mortality in the uremic patient--what does it teach for
      other risk factors in the non-renal patient?
AB  - A high rate of cardiovascular death in renal patients, particularly patients with
      endstage renal failure, has not been well appreciated in the past. It is obvious
      that cardiovascular lesions are more severe than can be explained by the
      classical risk factors of elevated blood pressure and dyslipidemia. In renal
      failure, a number of pathomechanisms are operative which may be paradigms of more
      general relevance, e.g. activation of the renin and sympathetic system,
      inhibition of the vasoconstrictor NO system, left ventricular hypertrophy in
      excess of what is expected for high blood pressure. A paradox inverse relation
      between lipid concentrations and cardiovascular death, i.e. a protective effect
      of hyperlipidemia, in dialysed patients, presumably results from the confounding
      effect of malnutrition, high lipid levels being a substitute marker of adequate
      nutrition.

PMID- 7731892
TI  - New insight into genetic mechanisms in renal disease.

PMID- 7731893
TI  - Calcium antagonists and the kidney--what are the perspectives in 1994?

PMID- 7731894
TI  - [Ketanserin decreases erythropoietin concentration in hemodialyzed patients on
      rHuEPO therapy].
AB  - Serotonergic mechanisms are partially responsible for changes in haemostasis and
      blood pressure rise in haemodialyzed patients treated with recombinant human
      erythropoietin (rHuEPO). Ketanserin--an antagonist of platelet and blood vessel
      serotonin receptors, given concomitantly to patients on rHuEPO therapy, prevents
      certain changes in haemostasis. Preliminary observations suggest that ketanserin
      also inhibits an increase in haemoglobin and haematocrit. So far there have been
      no reports on ketanserin affecting erythropoiesis. We studied an influence of the
      2-week oral ketanserin administration on some haematologic parameters, serum
      erythropoietin concentration, blood pressure and relevant biochemical blood
      indexes in 15 haemodialyzed patients treated with rHuEPO for 32 weeks. We found a
      significant fall in serum EPO concentration (p < 0.005) measured with the ELISA
      technique that correlated positively (r = 0.629) with a decrease in erythrocyte
      count (p < 0.005). Haemoglobin concentration followed the same pattern (p <
      0.005). The previously normal bleeding time prolonged significantly (p < 0.02)
      after ketanserin therapy. There were no changes in plasma iron and ferritin
      concentration, total iron binding capacity, transferrin saturation index,
      calcium, phosphorus and bilirubin concentration nor reticulocytosis. The
      decrement in EPO concentration did not affect peripheral blood platelet or
      leukocyte counts. The 14-day treatment with ketanserin did not influence arterial
      blood pressure in the patients. The study shows that ketanserin administered to
      haemodialyzed patients on long-term rHuEPO therapy induces a decrease in
      erythropoietin concentration and inhibits erythropoiesis. This phenomenon seems
      to result from diminished endogenous hormone synthesis caused by ketanserin.

PMID- 7731895
TI  - [Professor Franciszek Kokot].

PMID- 7731896
TI  - [Circadian rhythm of pituitary-thyroid hormones in patients with chronic renal
      failure treated by hemodialysis].
AB  - In 30 dialyzed patients with end stage renal failure and and in 15 healthy
      subjects the circadian rhythm was studied of the hormonal secretion of the
      pituitary-thyroid axis. (TSH, T3, T4). Venous blood was sampled every 6 hours
      from subjects following their regular way of life. The dialyzed patients with end
      stage renal failure present the normal circadian rhythm of pituitary-thyroid
      hormones secretion was preserved (despite differences in measure and amplitude)
      and erythropoietin administration did not change the pattern.

PMID- 7731897
TI  - [The influence of intermittent peritoneal dialysis on free and total thiamine
      concentration in plasma and erythrocytes of patients with end stage renal
      disease].
AB  - The concentration of free and total thiamine in plasma (PFTh and PTTh) and in
      erythrocytes (EFTh and ETTh) was determined in 20 healthy volunteers and in 8
      patients suffering from ESRD treated (60 hrs/week) with IPD. Venous blood for
      determinations was taken immediately before and at the end of the subsequent 20
      hrs PD as well as, after 12 and 48 hrs elapsed from the completion of this
      procedure. Thiamine was determined using fluorimetric method. Mean concentration
      of PFTH and PTTh as well as ETTh of patients before dialysis was found to be low,
      but did not differ significantly from those found in the group of healthy
      volunteers. Mean value of EFTh before PD was statistically lower than in normals
      (p < 0.05). After dialysis lasting 20 hrs a significant lowering of the
      concentration of PFTH (p < 0.001) and PTTh (p < 0.01) has been observed, whereas
      the concentration of EFTh and ETTh significantly increased (p < 0.05). After 12
      and 48 hrs elapsed from the completion of dialysis a statistically significant
      increase in PFTh and PTTh concentration has been noted contrasting with those in
      EFTh and ETTh, where it felt down. Nevertheless these values in plasma and
      erythrocytes after 48 hrs from the completion of dialysis did not differ
      significantly from those found at the beginning of the determination. We conclude
      that IPD is a procedure exerting short-term lowering of the plasma thiamine
      concentration with simultaneous increase in those in erythrocytes concentration.
      Further studies are indispensable to clarify the problem of thiamine
      supplementation in patients treated with PD.

PMID- 7731898
TI  - [Some indices of peripheral blood oxidative metabolism during acetate and
      bicarbonate hemodialysis in patients with chronic uremia].
AB  - Whole blood superoxide anion generation, erythrocyte superoxide dismutase (SOD-1)
      and catalase activities and erythrocyte and plasma malonyldialdehyde
      concentrations were evaluated during cuprophane hemodialysis using bicarbonate
      and acetate dialysate. Superoxide anion generation by resting phagocytes was
      found to be significantly higher during bicarbonate hemodialysis, while its
      generation by opsonized zymosan--stimulated phagocytes did not differ between
      hemodialyses with both kinds of dialysates. Changes in the erythrocytes SOD-1
      activities, found in the initial period of hemodialysis, were independent of the
      kind of dialysate, while erythrocyte catalase activity was higher during acetate
      hemodialysis in comparison with bicarbonate one. The kind of dialysate did not
      affect extent of erythrocyte membrane lipid peroxidation, while plasma lipid
      peroxidation was lower during acetate hemodialysis in comparison with bicarbonate
      one. In vitro studies with blood cells incubated with acetate or bicarbonate ions
      in concentrations, which are observed in vivo during hemodialysis, suggest that
      probably these ions do not directly affect superoxide anions generation,
      erythrocyte SOD-1 and catalase activities and erythrocyte membrane lipid
      peroxidation.

PMID- 7731899
TI  - [Use of urea kinetic modeling in patients on maintenance hemodialysis].
AB  - The effect of urea kinetic modeling (u.k.m.) application on dialysis efficiency
      and metabolic status was evaluated in 50 maintenance dialyzed patients. U.k.m.
      sessions were performed once a month based on the self-developed computer program
      to control dialysis. The dialysis index (Kt/V), the time averaged concentration
      (TAC), protein catabolic rate (pcr) and dialysis effectiveness (Ct/Co) were
      evaluated and the results obtained at the beginning and after 2, 4, and 8 months
      of the study were compared. Kt/V had risen significantly in the modeled patients
      from 1.04 to 1.24 and was accompanied by 12% Ct/Co increase of urea removal after
      8 months. The tendency of the moderate (non significant) decrease of TAC from
      54.57 to 52.48 mg% BUN was observed during the study. According to the NCDS
      criteria the percentage of adequately dialyzed patients increased from 42% at the
      beginning to 64% after 80 months; underdialyzed patients decreased from 16% to 6%
      and malnourished also from 16% to 6%, respectively, after u.k.m. application.
      Dialysis effectiveness for creatinine and uric acid described by Ct/Co for the
      above after 4 and 8 months was significantly increased when compared with the
      results obtained at the beginning of the study. These results indicate that
      u.k.m. application allowed to take control over uremic toxemia and improved
      dialysis adequacy in patients on maintenance dialysis. Protein catabolic rate in
      studied patients increased from 1.18 to 1.24 g/kg/per day during the study and it
      was accompanied by a total blood protein and serum albumin increase. This could
      indicate improvement of the nutritional status of dialyzed subjects.

PMID- 7731900
TI  - [DNA metabolism in lymphocytes of patients with lupus nephropathy].
AB  - DNA metabolism in lymphocytes was evaluated in patients suffering from the
      nephrotic syndrome decompensation, basing on measurement of endonucleases
      (DNases) activity in these cells. The examination involved 17 patients, aged 27.7
      +/- 7.11 with clinical and biochemical active disease, all with the nephrotic
      syndrome decompensation and erythrocytes in urine. A significant rise in the
      enzyme activity was observed in T and B lymphocytes (p < 0.001) in all the
      patients, with a distinct 3-fold increase in enzyme activity in B lymphocytes,
      when compared with the other cell populations. To elucidate the nature of the
      observed changes in DNases activity in systemic lupus erythematosus, nucleus
      proteins of the cells were separated electrophoretically in acrylamide gradient
      with immobilized DNA. Degradation processes in nucleic acids were considerably
      more efficient than the DNA synthesis in B lymphocytes of these cells. A smaller
      increase in the enzyme activity in T cells than in B lymphocytes results
      exclusively from more intense catabolism of nucleic acids not parallel to the
      intensified DNA synthesis in these cells.

PMID- 7731901
TI  - [Effect of treatment of arterial hypertension on renal function in patients with
      imminent and overt diabetic nephropathy].
AB  - The effect was studied of blood pressure lowering treatment on renal failure and
      albuminuria (UAE) in patients with type I diabetes (IDDM) and imminent
      nephropathy as well as in patients with over diabetic nephropathy. The group of
      24 patients with imminent nephropathy was subdivided: 1. twelve patients with
      borderline or overt hypertension with mean BP lowered not below 100 mmHg, and 2.
      twelve patients with BP within the normal limits, taking no hypotensive agents.
      In the other group of 12 patients with overt diabetic nephropathy hypertension
      was lowered below 105 mmHg and kept so for at least two years. All patients
      estimated their glycemia and glycosuria by themselves, ate 0.8 g protein/kg/24 h
      and about 100 mmol Na/24h. Under hospital conditions the following were
      estimated: albuminuria, glomerular filtration rate (51Cr EDTA) and effective
      renal blood flow (131I hippurate). The same examinations were repeated 1 year and
      2 years later. The lowering of BP below 100 mmHg in patients with imminent
      diabetic nephropathy significantly lowered microalbuminuria without changing GFR,
      ERPF despite good or satisfactory compensation of diabetes. Maintaining BP below
      105 mmHg for 2 years did not prevent the patients with overt nephropathy to
      develop progressive renal failure despite the rate of GFR deterioration and of
      the increase of albuminuria slowed down.

PMID- 7731902
TI  - [Monthly intravenous cyclophosphamide in the treatment of lupus nephritis].
AB  - 21 patients with severe active lupus nephritis (LN) were treated with intravenous
      cyclophosphamide monthly doses 0.75 g/m2. The effects were compared with the
      results obtained in 22 patients by the oral prednisone administration in the dose
      1 mg/kg/day. Both groups were not significantly different as regards the initial
      intensity of the LN symptoms. Complete or partial remission occurred in 17
      patients (80.9%) receiving intravenous cyclophosphamide. End-stage renal failure
      in 2 patients and moderate renal insufficiency in other 2 patients from that
      group. In the prednisone treated group complete or partial remission was observed
      in 13 subjects (59.1%). The significant deterioration of the renal function
      occurred in 9 patients, in 6 into the phase of a moderate renal insufficiency and
      in 3 patients to the end-stage kidney failure. Additionally, the significant
      increase of the total serum complement activity and of the plasma platelets count
      was observed in the cyclophosphamide group, whereas those indicators did not
      improve in the patients receiving prednisone. The of intravenous pulse
      cyclophosphamide exhibits an advantage in the treatment of severe proliferative
      LN.

PMID- 7731903
TI  - [Some clinical aspects of erythropoietin action used at doses not affecting
      erythropoiesis in hemodialysed patients].
AB  - Erythropoietin has become a crucial point in treatment of anaemia in patients
      with chronic renal failure. Recently a very important point of concern are the
      non hematological aspects of its action. The aim of presented study was to
      evaluate the biochemical and clinical effects of using erythropoietin at doses
      not influence hemopoiesis. 10 hemodialysis patients with stable hemoglobin and
      hematocrit levels, were given erythropoietin at dose of 7-10U/kg.b.w./d--the dose
      not affecting erythropoiesis. Erythropoietin was administered subcutaneously, 3
      times a week, for 12 weeks. In this way, we tried to evaluate the direct effects
      of erythropoietin action, not associated with a correction of anemia. After the
      therapy a statistically significant decrease was seen of total cholesterol (p <
      0.01), LDL-cholesterol (p < 0.01) in serum of these patients. The concentration
      of triglycerides, HDL-cholesterol, glucose and insulin changed in a variable
      mode. We did not find any significant changes in hemoglobin and hematocrit
      levels, but despite of that we observed a significant decrease of lactate (p <
      0.01). It seems that the global result of all mentioned changes was a great
      improvement in the "quality of life" of this group of patients.

PMID- 7731904
TI  - [Evaluation of bone mineralization in patients on maintenance hemodialysis].
AB  - Bone loss and bone formation and mineralization abnormalities resulting from
      disturbances in calcium and phosphorus metabolism are frequent in chronic renal
      failure. Haemodialysis permits long-term survival of patients with end-stage
      renal disease. This is the reason, why renal osteodystrophy became an important
      diagnostic and therapeutical problem. Very low occurrence of fractures among
      haemodialysed patients in our clinic, stimulated our efforts to elucidate the
      causes of this phenomenon. The aim of this study was to compare bone mineral
      densities in haemodialysed patients and healthy volunteers. 47 patients on
      maintenance haemodialysis (16 F, 31 M) and 55 healthy volunteers (33 F, 22 M)
      with normal renal function were investigated. Endocrinopathy or any other
      diseases that could cause changes in bone metabolism were excluded. Age
      distribution in both groups was similar. Patients maintained on low sodium and
      phosphorus diet additionally were supplemented with large doses of calcium
      carbonate. Haemodialyses were performed using reverse-osmosis water. BMD (Bone
      Mineral Density) was measured using QCT (Quantitative Computed Tomography) and
      was expressed as an average hydroxyapatite content in lumbar vertebraes L1-L4.
      The obtained results indicate high BMD of vertebral bones in haemodialysed
      patients from our Dialysis Department. BMD was similar to that observed in
      healthy volunteers. This could at least partially explain low occurrence (2 in
      142 pts-years) of fractures in ou uraemic patients. However we were unable to
      point exactly the simple factor responsible for this positive phenomenon. We hope
      that introduction of our haemodialysis scheme can help patients to avoid renal
      osteodystrophy.

PMID- 7731905
TI  - The pathogenesis of chronic renal insufficiency in renal vasculopathies.
AB  - Comparative clinical and morphological investigations on the pathogenesis of
      chronic renal insufficiency in various types of renal vasculopathy revealed the
      following: 1) Compensated benign nephrosclerosis, with hyalinosis of the walls of
      the afferent vessels, does not lead to renal insufficiency, since relatively few
      glomeruli, mostly subcapsular, become obliterated in this disease. 2) In
      decompensated benign nephrosclerosis, in which not only the afferent vessels but
      also the glomeruli and the cortical interstitium are involved, there is a
      significant positive correlation between the relative width of the renal cortical
      interstitium and the serum creatinine concentration and a significant negative
      correlation between the relative volume of the postglomerular capillaries and the
      serum creatinine concentration, as in the primary glomerulopathies. 3) In primary
      malignant nephrosclerosis, which is always accompanied by haemolytic-uraemic
      syndrome, the relative width of the cortical interstitium is not related to the
      serum creatinine concentration. Chronic renal insufficiency develops in this
      disease as a result of a fall in glomerular filtration rate to inadequate levels
      due to impairment of renal perfusion by stenotic changes in the preglomerular
      vessels. 4) In secondary malignant nephrosclerosis, which is never accompanied by
      haemolytic-uraemic syndrome, there is, as in the primary glomerulopathies, a
      significant positive correlation between the relative width of the renal cortical
      interstitium and the serum creatinine concentration and a significant negative
      correlation between the relative capillary volume and the serum creatinine
      concentration. 5) In decompensated benign nephrosclerosis the severity of the
      renal insufficiency depends largely on the degree of obliteration of the
      postglomerular capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731906
TI  - Antifungal drugs.

PMID- 7731907
TI  - Autism and the pervasive developmental disorders: Part 1.

PMID- 7731908
TI  - Acute renal failure: therapy.

PMID- 7731909
TI  - Diaper dermatitis.

PMID- 7731910
TI  - Infective endocarditis.

PMID- 7731911
TI  - Index of suspicion. Case 1. Diagnosis: Ventricular myxoma with pulmonary outflow
      tract obstruction.

PMID- 7731912
TI  - Index of suspicion. Case 2. Diagnosis: Acute lymphoblastic leukemia.

PMID- 7731913
TI  - Index of suspicion. Case 3. Diagnosis: Choledochal cyst.

PMID- 7731914
TI  - Consultation with the specialist. Adolescent social development.

PMID- 7731915
TI  - Intraspecific variation of Taenia taeniaeformis as determined by various
      criteria.
AB  - The intraspecific variation of four laboratory-reared isolates of Taenia
      taeniaformis the SRN and KRN isolates from Norway rats, Rattus norvegicus,
      captured in Japan and Malaysia, respectively; the BMM isolated from a house
      mouse, Mus musculus, captured in Belgium; and the ACR isolate from a gray red
      backed vole, Clethrionomys rufocanus bedfordiae, captured in Japan was examined
      by various criteria. Eggs of each of the four isolates were orally inoculated
      into several species of intermediate host. They were most infective to the rodent
      species from which the original metacestode of each isolate had been isolated in
      the field, and only the ACR isolate was infective to the gray red-backed vole.
      Although little difference was found between the SRN, KRN, and BMM isolates by
      the other criteria, including the morphology of rostellar hooks, the protein
      composition of the metacestode, and restriction endonuclease analysis of DNA, the
      ACR isolate was clearly different from the others. It was considered that the ACR
      isolate was independent as a strain distinct from the other three isolates.

PMID- 7731916
TI  - Uterine atrophy in chronic murine toxoplasmosis due to ovarian dysfunction.
AB  - Uterine atrophy is a conspicuous finding in Nya:NYLAR female mice chronically
      infected with Toxoplasma gondii. Administration of 17B-estradiol to infected mice
      induced a vigorous uterotropic response, i.e., an increase in uterine weight, in
      endometrial hypertrophy and proliferation, and in the activity of three estrogen
      regulated uterine enzymes. These findings rule out a parasite-induced
      refractoriness of the uterus to estrogen and point to ovarian dysfunction
      (hypogonadism) as the immediate cause of the uterine atrophy.

PMID- 7731917
TI  - Etiology of ovarian dysfunction in chronic murine toxoplasmosis.
AB  - Ovarian dysfunction develops in Nya:NYLAR mice chronically infected with
      Toxoplasma gondii. To differentiate between primary ovarian failure and pituitary
      gonadotropin insufficiency, we (a) monitored ovarian responsiveness to pregnant
      mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) and (b)
      assessed endogenous pituitary gonadotropin capacity by the degree of ovarian
      compensatory hypertrophy (OCH) developing after unilateral ovariectomy (ULO).
      PMSG stimulated vigorous folliculogenesis and estrogen synthesis, but not
      ovulation. HCG given 3 days after PMSG induced "superovulation" within 16 h.
      These observations indicate the absence of the critical preovulatory surge of
      endogenous luteinizing hormone (LH) from the pituitary. In addition, ULO did not
      result in compensatory hypertrophy of the contralateral ovary, an indication of
      follicle-stimulating hormone (FSH) insufficiency. We hypothesize that cytokines
      released peripherally in response to the parasite reached the hypothalamus and
      initiated a sequence of events that inhibited the pulsatile release of
      gonadotropin-releasing hormone (GnRH), leading to the subsequent impairment of
      the pituitary-ovarian axis.

PMID- 7731918
TI  - The involvement of terminal carbohydrates of the mammalian cell surface in the
      cytoadhesion of trichomonads.
AB  - In the present study the parental cells and glycosylation mutants of Chinese
      hamster ovary (CHO) cells were used to analyze the influence of surface
      carbohydrates on the cytoadhesion of trichomonads. Trichomonas vaginalis and
      Tritrichomonas foetus were allowed to interact with host cells for 2 h at 37
      degrees C. Alternatively, CHO cells were treated with 10 mM periodate prior to
      the assays. Both trichomonads adhered to all CHO cell clones tested. A remarkable
      difference could be observed between the cytoadhesion of T. vaginalis and T.
      foetus. Sialic acid residues present on the surface of CHO cells may favor the
      cytoadhesion of T. foetus while hampering that of T. vaginalis. The specificity
      of the parasite cytoadhesion was further investigated. Sialic acid, mannose, and
      galactose as well as mannose, galactose, and N-acetylglucosamine added to the
      interaction medium at 50, 100, and 200 mM were capable of significantly
      inhibiting the cytoadhesion of each trichomonad species. Periodate treatment of
      target cells also induced decreases in the cytoadhesion of the trichomonads.
      These results strongly suggest an important role for host-cell surface
      glycoconjugates during the cytoadhesion of trichomonads. In addition, they also
      point out the presence of "lectin-like" molecules on the surface of both T.
      vaginalis and T. foetus.

PMID- 7731919
TI  - The effects of subclinical fasciolosis on hepatic secretory function in sheep.
AB  - The effects of subclinical fasciolosis at various stages of its development on
      bile flow and bile acid secretion and on the hepatobiliary transport of bilirubin
      were investigated in experimentally infected sheep. Bile flow was significantly
      reduced by weeks 6-14 postinfection. This was accompanied by a decrease in bile
      acid secretion by weeks 6-8. Serum AST and GLDH activities and serum bile acid
      concentration were significantly elevated from weeks 6 to 14. Total serum
      bilirubin was maximally increased at 6 weeks postinfection and remained elevated
      at weeks 8 and 14. Increases corresponded to both unconjugated and conjugated
      fractions, although the conjugated/total bilirubin ratio was enhanced in all
      infected animals. Biliary bilirubin secretion declined from weeks 6 to 14. No
      alteration was detected in either uridine diphosphate (UDP)
      glucuronosyltransferase activity, cytochrome P-450 concentration, or
      hematological markers of hemolysis. This study shows that the migration of
      immature flukes in the course of ovine fasciolosis causes a cholestatic
      phenomenon responsible for changes in serum and biliary bilirubin levels.

PMID- 7731920
TI  - Use of enzyme-linked immunosorbent assay and enzyme-linked immunoelectrotransfer
      blot for the diagnosis and monitoring of neurocysticercosis.
AB  - A total of 70 proven cases of neurocysticercosis from la Reunion (Indian Ocean)
      were studied with enzyme-linked immunoassay (ELISA) and immunoelectrotransfer
      blot (EITB) to detect specific antibodies in serum and cerebrospinal fluid (CSF).
      Absorbance levels of antibody to crude Taenia solium cyst extract as an antigen
      were compared with EITB banding-pattern and computed tomography-scan results. The
      EITB analysis of sera and CSF from patients with active neurocysticercosis,
      confirmed with characteristic brain-scan imaging and highest ELISA absorbance,
      regularly revealed two bands with molecular weights of 13 and 14 kDa,
      respectively. These low-molecular-weight fractions are potential markers of
      active cerebral cysticercosis, a result obtained in the simple epidemiological
      situation of La Reunion (Indian Ocean). A parallel study is underway in
      Madagascar, where cross-reactivities with other parasitic diseases, including
      Schistosoma infections, may interfere.

PMID- 7731921
TI  - Seroprevalence of Fasciola hepatica infection in sheep in northwestern Spain.
AB  - To estimate the prevalence of Fasciola hepatica infection in sheep in the Leon
      province (northwestern Spain), we conducted a survey between October 1992 and May
      1993. A total of 767 samples of feces and serum were collected from sheep over 1
      year of age belonging to 152 flocks randomly selected from the 4 natural regions
      of Leon province. Samples were analyzed by a standard coprological sedimentation
      method and an indirect enzyme-linked immunosorbent assay (ELISA) using excretory
      secretory products from F. hepatica as the antigen. The results showed the
      feasibility of using the indirect ELISA to facilitate the serodiagnosis of ovine
      fasciolosis in seroepidemiology studies (95% sensitivity and > 99% specificity).
      No serological cross-reaction with infection by the trematode Dicrocoelium
      dendriticum was found. Furthermore, a statistically significant association was
      demonstrated between the mean flock prevalence results as determined by ELISA
      (77.6%) and by coprological examination (23.7%; P < 0.001). Differences in the
      results obtained by the two diagnostic methods could have been due to
      fluctuations in the numbers of fluke eggs detected in feces and to the
      persistence of specific antibodies in serum after an efficacious fasciolicide
      treatment. The median number of F. hepatica eggs detected per gram of feces was
      10 (range, 5-450 eggs/g feces). The geographical distribution of F. hepatica
      infection in Leon province was similar in all natural regions, probably due to
      the observation that meteorological conditions are not limiting for the
      maintenance of the parasite life cycle in any area of the province and to the
      abundance of irrigated areas together with the lack of planned control
      strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731922
TI  - Disaccharidase activity in male and female C57BL/6 mice infected with Giardia
      muris.
AB  - To elucidate the contribution of host and parasite factors in induction of small
      intestinal disaccharidase deficiency in giardiasis, we determined the activity of
      four enzymes in male and female C57BL/6 mice infected with Giardia muris. Both
      male and female mice exhibited significant disaccharidase deficiency as shown by
      decreases in the activities of lactase, sucrase, trehalase and maltase on day 10
      after infection. However, by 20 days after infection the females had normal
      enzyme activities, whereas those in males remained significantly reduced.
      Prolonged disaccharidase deficiency in the males was related to the course of the
      primary infection where males had higher parasite loads in the small intestine
      than did females on day 20 after infection. By day 40 after the primary infection
      the enzyme activities had returned to normal levels and were similar in male and
      female mice. Secondary exposure of mice to either the infective cysts or a crude
      extract of the trophozoites caused disaccharidase deficiency. The females had
      lower activities of sucrase and trehalase as compared with males after the
      challenge. Thus, during the primary infection, disaccharidase deficiency was
      strongly associated with parasite number, whereas after challenge infections the
      more resistant females had lower enzyme activities in the small intestine than
      did males.

PMID- 7731923
TI  - Entamoeba histolytica autochthonous isolates from mentally retarded Italian
      patients.
AB  - A total of 77 mentally retarded male inpatients residing in a psychiatric
      institution in northern Italy were screened for the presence of stool parasites,
      Entamoeba histolytica particularly. Parasitological stool examination showed
      Entamoeba spp. (E. histolytica and/or E. dispar) in 26 cases (33.7%). In vitro
      culture on Robinson's medium was positive in 16 cases (61.1%); in 11 cases we
      could stabilize and clone the isolates and proceed to electrophoretic assays. In
      all cases, patterns of pathogenic zymodemes were found (zymodeme II, 3 isolates;
      zymodeme XII, 4 isolates; zymodeme XIV, 4 isolates). All isolates were therefore
      identified as E. histolytica.

PMID- 7731924
TI  - Cyclic nucleotide changes induced in human leukocytes by a product of axenically
      grown Entamoeba histolytica that inhibits human monocyte locomotion.
AB  - Pulse exposure of human mononuclear phagocytes to the monocyte locomotion
      inhibitory factor produced by Entamoeba histolytica (i.e., the 369- to 765-Da
      chromatographic fraction obtained from the supernatant fluid of axenically grown
      E. histolytica) led to a swift increase in the intracellular concentration of
      adenosine 3':5' cyclic monophosphate (cAMP). A weaker response was observed in
      human polymorphonuclear leukocytes, the locomotion of which, however, is not
      inhibited by this amebic factor. The same chromatographic fraction obtained from
      the axenic medium control lacked this effect, at least upon mononuclear
      phagocytes. On the other hand, both the monocyte locomotion-inhibitory factor and
      the axenic medium control, possibly through shared cultured medium components,
      induced comparable increases in guanosine 3':5' cyclic monophosphate (cGMP) in
      human mononuclear phagocytes and in polymorphonuclear leukocytes, thus suggesting
      that the latter-nucleotide is not critical for the leukotactic inhibitory
      phenomenon. Our results suggest that like other leukotactic inhibitors, the
      monocyte locomotion-inhibitory factor produced by E. histolytica operates through
      modulations of intracellular cAMP.

PMID- 7731925
TI  - Myxosporidia infecting some Nile fishes in Egypt.

PMID- 7731926
TI  - Chaperonin-like repeats in a 34-kDa Plasmodium berghei phosphoprotein.

PMID- 7731927
TI  - [13C]-nuclear magnetic resonance spectral profiles of serum from normal and
      Echinococcus granulosus-infected mice: a kinetic study.

PMID- 7731928
TI  - Electrical field-stimulated release of L-[G-3H]-glutamate from tissue slices of
      the cestode Hymenolepis diminuta.
AB  - The release of preloaded [3H]-L-glutamate by tissue slices of Hymenolepis
      diminuta was examined by the technique of electrical field stimulation. For
      tissues slices in balanced saline, a high-field strength of 1.78 A resulted in a
      highly elevated increase in the rate of release of radiolabel, which was
      suppressed in calcium-free saline. This technique may prove useful for screening
      helminth tissues for potential neurotransmitters.

PMID- 7731929
TI  - Cloning of a signal-recognition-particle subunit of Schistosoma mansoni.

PMID- 7731930
TI  - Long-term survival of Plasmodium sporozoites in vitro.

PMID- 7731931
TI  - Eimeria spp. of the domestic fowl: analysis of genetic variability between
      species and strains using DNA polymorphisms amplified by arbitrary primers and
      denaturing gradient-gel electrophoresis.
AB  - The genetic relatedness of 5 Eimeria spp. of the domestic fowl, including 11
      strains of E. acervulina, 2 strains of E. tenella and 1 precocious line of E.
      acervulina, was assayed by means of random amplified polymorphic DNA (RAPD) and
      denaturing gradient-gel electrophoresis (DGGE). Seven different oligonucleotides
      were used to generate similarity coefficients for the species and strains of
      Eimeria infecting chickens. Between 1 and 13 DNA segments, depending on the
      species/strain-primer combination, were amplified with the various primers.
      Amplification products ranged in size from 0.16 to 3.8 kb. E. acervulina strains
      demonstrated two to four major common bands unique to the species. These strains
      also exhibited major and minor differences in their DNA patterns. Band-match
      analyses from both polyacrylamide and denaturing gradient gels were used to
      calculate similarity coefficients for the Eimeria spp. and strains tested.
      Species differences, readily detected upon examination of DNA banding patterns,
      gave similarity coefficients of 4%-38% and 3%-18% when analyzed by polyacrylamide
      and denaturing gradient-gel electrophoresis, respectively. A similar analysis of
      E. acervulina strains, yielded similarity coefficients of 55%-95% and 51%-85%,
      respectively. The differences observed between both species and strains were
      greater when the RAPD-assay products were analyzed via DGGE, indicating that a
      combination of these two techniques may provide a more stringent analysis of the
      genetic relatedness of these coccidia.

PMID- 7731932
TI  - Acanthamoeba sp. from the Philippines: electron microscopy studies on naturally
      occurring bacterial symbionts.
AB  - The isolation of two plasmid-like circular DNAs, measuring 52 and 42 kbp, from an
      Acanthamoeba sp. from the Philippines has led to the demonstration of a bacterial
      endosymbiont occurring in this free-living amoeba. The 52-kbp band hybridized
      with a short sequence of cytochrome b gene and was identified as the
      mitochondrial DNA, whereas the 42-kbp band was identified as plasmid DNA of the
      bacterial symbionts on the basis of electron microscopy. The endosymbionts are
      gram-negative, rod-shaped bacteria measuring approximately 1.3 x 0.43 microns and
      numbering about eight to ten cells per section. They are randomly distributed in
      both cysts and trophozoites and are surrounded neither by a phagolysosomal
      membrane nor by a clear or electron-translucent region. The endosymbiont membrane
      appears to have a close association with ribosomes, which are seen to be more
      concentrated within the vicinity of the symbionts than elsewhere within the
      cytoplasm. Attempts to grow the symbionts and the amoebae separately have failed.

PMID- 7731933
TI  - Paget's disease of the nipple and angiosarcoma of the breast following excision
      and radiation therapy for carcinoma of the breast.
AB  - We report a case of bilateral angiosarcomas developing in breasts after radiation
      therapy. The angiosarcomas developed 7 years after the first dose and 3 years
      after the last dose of radiation. In addition, Paget's disease of the nipple was
      diagnosed in the right breast. c-neu overexpression was noted in the
      adenocarcinoma but not in the angiosarcoma. Neither tumor was immunoreactive for
      c-k-ras. The oncogenic expression of the radiation-induced angiosarcoma was
      different from that of the radiation-resistant adenocarcinoma. The simultaneous
      occurrence of angiosarcoma and Paget's disease of the nipple has not been
      reported previously. The importance of recognizing Paget's disease in post
      irradiated breasts and complications of breast conservation therapy are stressed.

PMID- 7731934
TI  - Schwannomas.

PMID- 7731935
TI  - Cell proliferation and apoptosis in normal and pathologic human adrenal.
AB  - Cell proliferation and programmed cell death play important roles in the
      maintenance of tissue dynamics. The adrenal cortex has been known as a cell
      renewal tissue. We studied cell proliferation by Ki67 immunostaining and
      programmed cell death or apoptosis by a recently developed 3'-OH nick end
      labeling technique. Fifteen cases of normal human adrenal; 22 cases of
      adrenocortical adenoma including Cushing's adenoma (five cases), aldosteronoma
      (nine cases), and nonfunctioning adenoma (eight cases); and six cases of
      adrenocortical carcinoma were examined. In normal adrenal cortex, Ki67
      immunoreactivity was predominantly observed in the zona fasciculata in all the
      cases examined, whereas cortical cells positive for nick end labeling were
      present in the zona reticularis in all cases and in the zona glomerulosa in five
      cases. These results suggest that the "cell migration" or "centripetal" theory is
      also applicable in cell turnover of normal human adrenal cortex, and cortical
      cells may move in two directions, from fasciculata to reticularis and from
      fasciculata to glomerulosa in some instances. CD68-positive sinusoidal lining
      cells, which are considered to ingest the cells undergoing apoptosis, were
      present throughout the cortex. In adrenocortical adenoma, Ki67 immunoreactivity
      was observed in all cases, and tumor cells positive for nick end labeling were
      observed in 12 cases (Cushing's adenoma in three cases, aldosteronoma in four
      cases, and nonfunctioning adenoma in five cases). In adrenocortical carcinoma,
      Ki67 immunoreactivity was observed in all the cases, and its labeling index was
      significantly higher than that of normal adrenal and adrenocortical
      adenoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731936
TI  - Carcinoma of the penis.

PMID- 7731937
TI  - Prognostic significance of cellular proliferation in renal cell carcinoma: a
      comparison of synthesis-phase fraction and proliferating cell nuclear antigen
      index.
AB  - DNA aneuploidy has repeatedly been shown to be a significant prognostic indicator
      in renal cell carcinoma; however, few studies have emphasized the importance of
      measurements of cellular proliferation. This study evaluated 55 patients treated
      by radical nephrectomy and for whom clinical follow-up was available. There were
      36 men and 19 women with a mean age of 61 yr. Robson stage distribution was I, 38
      cases; II, five cases; and III, 12 cases. Flow cytometric analysis in 44 cases
      revealed 29 DNA diploid and 15 DNA aneuploid tumors with a median synthesis-phase
      fraction (SPF) of 4.4% (range 1.0 to 31.4%). The median proliferating cell
      nuclear antigen index was 3.9% (range 0.1 to 58.0%). There was a significant
      correlation between SPF and proliferating cell nuclear antigen index (R = 0.769)
      in the 33 cases in which both were available. Cellular proliferation, as
      determined by SPF, was a significant prognostic indicator (P < 0.02), but
      proliferating cell nuclear antigen index did not correlate with outcome (P >
      0.05). Other significant predictors in this study were Robson stage (P = 0.03)
      and nuclear grade (P = 0.0003). DNA ploidy did not correlate with outcome (P >
      0.05). We conclude that cellular proliferation, as measured by SPF analysis, is a
      significant predictor of outcome for renal cell carcinoma. Although the
      proliferating cell nuclear antigen index correlated with SPF, it did not achieve
      statistical significance as a prognostic indicator.

PMID- 7731938
TI  - Smooth muscle differentiation in normal human ovaries, ovarian stromal
      hyperplasia and ovarian granulosa-stromal cells tumors.
AB  - An immunohistochemical and ultrastructural investigation on the presence of
      "smooth muscle differentiation" in stromal ovarian tissue was carried out in 10
      adult granulosa cell tumors, six juvenile granulosa cell tumors, six
      thecoma/fibrothecomas, six cases of stromal hyperplasia, and in 10 normal
      ovaries. For immunohistochemistry, formalin-fixed paraffin-embedded tissues were
      processed using anti-alpha smooth muscle actin (alpha-SM actin) and anti-desmin
      as primary monoclonal antibodies. All adult granulosa cell tumors and juvenile
      granulosa cell tumors showed an intense alpha-SM actin immunoreaction, but weaker
      for desmin. Immunostain was diffuse in six out of 10 and five out of six adult
      granulosa cell tumors and juvenile granulosa cell tumors, respectively.
      Ultrastructurally, intermediate filaments focally converging into well developed
      desmosomes as well as peripheral bundles of myofilaments were documented both in
      adult granulosa cell tumors and juvenile granulosa cell tumors. In
      thecoma/fibrothecomas and stromal hyperplasia, alpha-SM actin and desmin
      expression was minimal or absent; on electron microscopy some "myoid" features
      and myofibroblasts were also seen. In normal ovaries, alpha-SM actin was found
      intensely expressed in the theca externa, focally identified in cortex-medulla,
      and unstained in the theca interna layer. Immunoreaction increased during
      folliculogenesis, going from a thin positive alpha-SM actin layer around
      secondary follicles to a strong diffuse stain in mature follicles. Our
      immunohistochemical and ultrastructural results indicate that a "smooth muscle
      differentiation" is a typical component of the specialized gonadal stromal
      tissue. A diffuse and focally alpha-SM actin is constantly present in granulosa
      cell tumors and thecoma/fibrothecomas, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7731939
TI  - Medullary carcinoma of the breast: interobserver variability in histopathologic
      diagnosis.
AB  - To assess the interobserver reproducibility for the diagnosis of medullary
      carcinoma of the breast (MC), 53 previously diagnosed MCs were independently
      assessed by six observers for growth pattern, nuclear grade (NG), inflammation,
      tumor margin, intraductal component, and glandular features. Tumors were
      reclassified as MC, atypical MC, or infiltrating ductal carcinoma according to
      the histopathologic criteria of Ridolfi et al. (Cancer 40:1365, 1977), Wargotz
      and Silverberg (Hum Pathol 19:1340, 1988), and Pedersen et al. (Br J Cancer
      63:591, 1991). NG was the most reproducible parameter, and tumor margin was the
      least, with consensus agreement by four of six observers for 49 (92%) and 26
      (49%) of cases, respectively. Utilizing the histopathologic criteria proposed by
      Ridolfi et al., Wargotz and Silverberg, and Pedersen et al., consensus diagnoses
      were achieved in 37 cases (70%), 46 cases (87%), and 51 cases (96%),
      respectively. A consensus diagnosis of MC in all three systems was unassociated
      with tumor size, axillary lymph node status or overall survival (median follow
      up: 89 mo). The consensus (or better) reclassification of 44/53 (83%), 35/53
      (66%), and 27/53 (51%) previously diagnosed MC as atypical MC or infiltrating
      ductal carcinoma by the criteria of Ridolfi et al., Wargotz and Silverberg, and
      Pedersen et al., respectively, suggests that MC was previously over-diagnosed.
      While the scheme of Pedersen et al. is the most reproducible, additional follow
      up information is necessary to determine the biological significance of this
      classification system. To minimize these difficulties in practice, pathologists
      should carefully adhere to published criteria and indicate the classification
      system utilized.

PMID- 7731940
TI  - Primary lymphomatous effusions in AIDS: a morphological, immunophenotypic, and
      molecular study.
AB  - Lymphomas were documented in pleural effusions or ascites in 18 human
      immunodeficiency virus-positive (HIV+) patients. Eleven of 12 with clinical data
      had acquired immunodeficiency syndrome before the diagnosis of lymphoma. In 13 of
      15 with data available, a body cavity was the site of initial presentation of
      lymphoma. Cytological subtypes were large cell immunoblastic, n = 7; large cell
      anaplastic, n = 6; and large cell NOS, n = 5. The high incidence of anaplastic
      large cell lymphoma and the conspicuous absence of Burkitt's lymphoma differ
      strikingly from HIV-associated lymphomas generally. Immunophenotypically, two
      cases were B-cell (CD19/20+, sIg+, CD/5-), one was T-cell (CD3+, CD5+, CD4+, CD8
      , CD19/20-, sIg-), and 15 were null (CD45+, HLA-DR+ CD19/20-, sIg-, CD3/5-). This
      83% incidence of null immunophenotype contrasts sharply with a 9% incidence among
      35 tissue-based lymphomas in HIV+ patients that were similarly studied and a 0%
      null immunophenotype among 11 lymphomatous effusions in patients without HIV risk
      factors. Seven of the 18 HIV-associated lymphomas expressed CD30. Four of five
      cases with null immunophenotype showed Ig heavy-chain gene rearrangement, two had
      clonal Epstein-Barr virus integration, and none had MYC protooncogene
      rearrangement. These cases belong to a subgroup of high-grade HIV-associated
      lymphomas that occur in the setting of profound immunosuppression in which
      immunoblastic morphology predominates and MYC rearrangement is encountered only
      infrequently.

PMID- 7731941
TI  - IgA nephropathy: a rare lesion in systemic lupus erythematosus.
AB  - We describe three patients with a well-established clinical diagnosis of systemic
      lupus erythematosus in whom the renal biopsy lesion unexpectedly is diagnostic of
      IgA nephropathy, not superimposed with any features of lupus nephritis. Whereas
      the clinical presentation and follow-up of renal disease in these patients
      indicate a relatively indolent course, the extrarenal manifestations of systemic
      lupus erythematosys have been relatively severe, and one patient died of systemic
      infection. IgA nephropathy hitherto has not been described in patients with
      systemic lupus erythematosus, and such an observation stresses that atypical
      glomerular lesions in these patients should raise the possibility of a nonlupus
      glomerulopathy.

PMID- 7731942
TI  - DNA image cytometry and the expression of proliferative markers (proliferating
      cell nuclear antigen and Ki67) in non-Hodgkin's lymphomas.
AB  - We have analyzed DNA content and proliferative activity in morphologically
      defined cell subpopulations of 74 non-Hodgkin's lymphomas (NHL) and 29 reactive
      lymph nodes using DNA image cytometry and antibodies to proliferative markers
      (proliferating cell nuclear antigen (PCNA) and Ki67). Thirteen (18.6%) of 70 NHL
      cases were aneuploid. The follicular center cell-derived lymphomas with DNA
      aneuploidy had DNA indices (DI) predominantly in the tetraploid region, whereas
      aneuploid high-grade (HG) NHL presented DNA histograms with multiple aneuploid
      stemlines. In aneuploid centrocytic-centroblastic (CB/CC) NHLs, DNA aneuploidy
      was found exclusively in centroblasts, whereas centrocytes in these cases were
      diploid. Percentages of cells in S and G2/M phase in chronic lymphocytic leukemia
      (CLL), immunocytoma (IC), centrocytic NHL (CC), and centrocytes from CB/CC were
      low (< 5%), whereas the respective values for centroblasts in CB/CC and in
      malignant cells of HG NHL were similar to those of large lymphoid cells in the
      reactive lymph nodes (mean, 39.5%, 36.6%, and 53.5%, respectively). The mean
      percentage of PCNA positive cells in CLL, IC, and CC was 4.9%. In the follicles
      of CB/CC NHLs there was, on average, 56.9% of PCNA positive centroblasts and 8.1%
      of PCNA positive centrocytes. In HG NHL, the mean percentage of PCNA positive
      lymphoma cells was 27.9%. A positive correlation was found between percentages of
      cells in S and G2/M phase and cells positive for PCNA (P < 0.001). There was also
      a significant correlation between percentages of Ki67 (mean, 19.2%) and PCNA
      positive cells (mean, 17.7%) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731943
TI  - Skin biopsy in allogeneic and autologous bone marrow transplant patients: a
      histologic and immunohistochemical study and review of the literature.
AB  - Histologic criteria and grading system for diagnosis of cutaneous manifestations
      of graft vs. host disease (GvHD) have been established, and the diagnosis of high
      grade GvHD is readily made by pathologists. There have been, however, increasing
      reports of skin rash occurring in patients treated with autologous bone marrow
      transplant (aBMT) that cannot be distinguished clinically or histologically from
      GvHD following allogeneic bone marrow transplant (alloBMT). We studied the
      histologic and immunohistochemical features of 25 skin biopsy specimens obtained
      from 22 patients with skin rashes who had undergone either aBMT or alloBMT, or
      who suffered from a malignancy. Tissue sections were immunoreacted with pan-T
      lymphocyte-associated antibody Leu 22 (CD43); pan-B antibody L26 (CD20);
      macrophage/myeloid antibody for CD68 antigens; and LN-3 antibody specific for HLA
      Class II antigens. The clinical suspicion of GvHD was confirmed in 8 of 10
      alloBMT patients. Seven of the 10 aBMT patients also clinically diagnosed to have
      GvHD, had histologic changes consistent with Grades I, II, or III. The rest of
      the patients showed changes consistent with drug reaction. T-cell lymphocytes
      (Leu22), macrophages (CD68), and HLA-DR expression on Langerhans cells were in
      general more prominent in allogeneic chronic GvHD, but this was not statistically
      significant. No significant differences were seen in the degree of HLA-DR
      expression on endothelial cells and keratinocytes in any of the groups. The
      current histologic criteria are inadequate to differentiate cutaneous GvHD
      following alloBMT from the skin rash occurring in the setting of aBMT.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7731944
TI  - Prevalence and nonspecificity of microvesicular fatty change in the liver.
AB  - Hepatic microvesicular fat (MVF) has been associated with clinical syndromes of
      liver failure (such as acute fatty liver of pregnancy and Reye's syndrome). We
      performed this pilot study to investigate the specificity and potential risk
      factors of MVF. Sections of the liver from 17 adult autopsies were snap-frozen,
      and Oil Red O (ORO)-stained sections were obtained. The presence of MVF in the
      ORO stains was analyzed in a semiquantitative manner: 3+ = > 90% liver parenchyma
      with MVF; 2+ = 25-90%; 1+ = 1-24%. H&E-stained liver sections were reviewed
      independently to determine the presence and extent of inflammation, fibrosis, and
      necrosis. Autopsy reports were reviewed for the gross findings; medical records
      were reviewed for demographic data, medical history, and, in particular,
      medication usage. The study consisted of 10 males and 7 females (15 white, 2
      black), with a median age of 76 years (range: 50-88). MVF was identified in 16
      patients (94%); it was infrequent (1+, 2+) in the majority, but 4 patients (24%)
      had 3+ MVF. MVF was not associated with the age or sex of the patients, liver
      weight, postmortem interval to examination, or other histologic features in the
      liver. None of the patients, including those with 3+ MVF, had a history of liver
      disease. All 4 patients with extensive MVF were using salicylates, as opposed to
      2 of 5 with 2+ MVF and 1 of 8 with 0 to 1+ MVF (P = 0.015). In this autopsy
      study, the prevalence of MVF was high, with 24% of patients having extensive
      MVF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7731945
TI  - Myometrial hyperplasia: proposed criteria for a discrete morphological entity.
AB  - Myometrial hyperplasia is not a well-established morphological entity. Technical
      obstacles regarding uterine weight, myometrial cellularity, and myometrial cell
      orientation have made it difficult to establish objective criteria for diagnosis.
      In this study, 15 slides that had been interpreted as within normal limits on
      routine examination were reevaluated because there were areas of myometrium that
      stood out as relatively blue on scanning magnification of H&E-stained sections.
      Morphometrically, they all had increased myometrial cellularity, compared with
      normal myometrium elsewhere on the same slide (P < 0.05), and an increased
      nucleus/cell ratio (P < 0.001). They occurred in three patterns. The diffuse
      inframucosal form and the subserosal plaque-like form sometimes corresponded to
      grossly detectable inframucosal bulges or subserosal ridges. There was also an
      occult, microscopic intramural pattern of myometrial hyperplasia, which differed
      from seedling leiomyomas by its lack of nodularity and compression of adjacent
      myometrium. We propose that these criteria may permit an objective diagnosis of
      myometrial hyperplasia. We believe that it will be of interest to explore the
      clinical significance, cell biology, and pathogenesis of this distinctive
      variation in myometrial structure.

PMID- 7731946
TI  - Seminar on breast tumors and tumor-like lesions.

PMID- 7731947
TI  - Inflammatory diseases of the gastrointestinal tract.

PMID- 7731948
TI  - Secondary structural predictions for the clostridial neurotoxins.
AB  - The primary structures of a family of ten clostridial neurotoxins have recently
      been deduced yet little information is presently available concerning their
      secondary or tertiary structures. Because the overall similarity percentage of
      multiply aligned sequences is high, the secondary structures of these
      metalloendopeptidases are also expected to be conserved. The neural net program,
      PHD (Rost and Sander, Proc. Natl. Acad. Sci. USA 90:7558-7562, 1993), predicted
      that the secondary structures of the neurotoxins were indeed conserved in both
      single and multiple sequence modes of analysis. Predictions for the amounts of
      helical, extended, and loop states from the single sequence analyses were
      consistent with previously published data from circular dichroism studies on some
      of these neurotoxins. In the single analysis mode, only the aligned regions were
      predicted to show conservation of the three-state structure. In contrast, the
      multiple sequence analysis predicted that a conserved state (variable loops) also
      exists in non-aligned regions. Alignments with the primary structure of the
      prototypic metalloendopeptidase thermolysin showed that about 25% of the residues
      within this enzyme are similar to those in the neurotoxins. A comparison of
      thermolysin's known secondary structure with the predictions from this study
      showed that about 80% of thermolysin's residues could be structurally aligned
      with those in the neurotoxins. These predictions provide the necessary framework
      to build a homologous low-resolution tertiary structure of the neurotoxin active
      site that will be essential in the development of synthetic inhibitors.

PMID- 7731949
TI  - Intrinsic secondary structure propensities of the amino acids, using statistical
      phi-psi matrices: comparison with experimental scales.
AB  - Today there are several different experimental scales for the intrinsic alpha
      helix as well as beta-strand propensities of the 20 amino acids obtained from the
      thermodynamic analysis of various model systems. These scales do not compare well
      with those extracted from statistical analysis of three-dimensional structure
      databases. Possible explanations for this could be the limited size of the
      databases used, the definitions of intrinsic propensities, or the theoretical
      approach. Here we report a statistical determination of alpha-helix and beta
      strand propensities derived from the analysis of a database of 279 three
      dimensional structures. Contrary to what has been generally done, we have
      considered a particular residue as in alpha-helix or beta-strand conformation by
      looking only at its dihedral angles (phi-psi matrices). Neither the identity nor
      the conformation of the surrounding residues in the amino acid sequence has been
      taken into consideration. Pseudoenergy empirical scales have been calculated from
      the statistical propensities. These scales agree very well with the experimental
      ones in relative and absolute terms. Moreover, its correlation with the average
      of the experimental scales for alpha-helix or beta-strand is as good as the
      correlations of the individual experimental scales with the average. These
      results show that by using a large enough database and a proper definition for
      the secondary structure propensities, it is possible to obtain a scale as good as
      any of experimental origin. Interestingly the phi-psi analysis of the
      Ramachandran plot suggests that the amino acids could have different beta-strand
      propensities in different subregions of the beta-strand area.

PMID- 7731950
TI  - Homology models of two isozymes of manganese peroxidase: prediction of a Mn(II)
      binding site.
AB  - The three-dimensional structures of two isozymes of manganese peroxidase (MnP)
      have been predicted from homology modeling using lignin peroxidase as a template.
      Although highly homologous, MnP differs from LiP by the requirement of Mn(II) as
      an intermediate in its oxidation of substrates. The Mn(II) site is absent in LiP
      and unique to the MnP family of peroxidases. The model structures were used to
      identify the unique Mn(II) binding sites, to determine to what extent they were
      conserved in the two isozymes, and to provide insight into why this site is
      absent in LiP. For each isozyme of MnP, three candidate Mn(II) binding sites were
      identified. Energy optimizations of the three possible Mn(II) enzyme complexes
      allowed the selection of the most favorable Mn(II) binding site as one with the
      most anionic oxygen moieties best configured to act as ligands for the Mn(II). At
      the preferred site, the Mn(II) is coordinated to the carboxyl oxygens of Glu-35,
      Glu-39, and Asp-179, and a propionate group of the heme. The predicted Mn(II)
      binding site is conserved in both isozymes. Comparison between the residues at
      this site in MnP and the corresponding residues in LiP shows that two of the
      three anionic residues in MnP are replaced by neutral residues in LiP, explaining
      why LiP does not bind Mn(II).

PMID- 7731951
TI  - Hydrophobic docking: a proposed enhancement to molecular recognition techniques.
AB  - In the classical procedures for predicting the structure of protein complexes two
      molecules are brought in contact at multiple relative positions, the extent of
      complementarity (geometric and/or energy) at the surface of contact is assessed
      at each position, and the best fits are retrieved. In view of the higher
      occurrence of hydrophobic groups at contact sites, their contribution results in
      more intermolecular atom-atom contacts per unit area for correct matches than for
      false positive fits. The hydrophobic groups are also potentially less flexible at
      the surface. Thus, from a practical point of view, a partial representation of
      the molecules based on hydrophobic groups should improve the quality of the
      results in finding molecular recognition sites, as compared to full
      representation. We tested this proposal by applying the idea to an existing
      geometric fit procedure and compared the results obtained with full vs.
      hydrophobic representations of molecules in known molecular complexes. The
      hydrophobic docking yielded distinctly higher signal-to-noise ratio so that the
      correct match is discriminated better from false positive fits. It appears that
      nonhydrophobic groups contribute more to false matches. The results are discussed
      in terms of their relevance to molecular recognition techniques as compared to
      energy calculations.

PMID- 7731952
TI  - Structural analysis of two crystal forms of lentil lectin at 1.8 A resolution.
AB  - The structures of two crystal forms of lentil lectin are determined and refined
      at high resolution. Orthorhombic lentil lectin is refined at 1.80 A resolution to
      an R-factor of 0.184 and monoclinic lentil lectin at 1.75 A resolution to an R
      factor of 0.175. These two structures are compared to each other and to the other
      available legume lectin structures. The monosaccharide binding pocket of each
      lectin monomer contains a tightly bound phosphate ion. This phosphate makes
      hydrogen bonding contacts with Asp-81 beta, Gly-99 beta, and Asn-125 beta, three
      residues that are highly conserved in most of the known legume lectin sequences
      and essential for monosaccharide recognition in all legume lectin crystal
      structures described thus far. A detailed analysis of the composition and
      properties of the hydrophobic contact network and hydrophobic nuclei in lentil
      lectin is presented. Contact map calculations reveal that dense clusters of
      nonpolar as well as polar side chains play a major role in secondary structure
      packing. This is illustrated by a large cluster of 24 mainly hydrophobic amino
      acids that is responsible for the majority of packing interactions between the
      two beta-sheets. Another series of four smaller and less hydrophobic clusters is
      found to mediate the packing of a number of loop structures upon the front sheet.
      A very dense, but not very conserved cluster is found to stabilize the transition
      metal binding site. The highly conserved and invariant nonpolar residues are
      distributed asymmetrically over the protein.

PMID- 7731953
TI  - A P-loop-like motif in a widespread ATP pyrophosphatase domain: implications for
      the evolution of sequence motifs and enzyme activity.
AB  - A conserved amino acid sequence motif was identified in four distinct groups of
      enzymes that catalyze the hydrolysis of the alpha-beta phosphate bond of ATP,
      namely GMP synthetases, argininosuccinate synthetases, asparagine synthetases,
      and ATP sulfurylases. The motif is also present in Rhodobacter capsulata AdgA,
      Escherichia coli NtrL, and Bacillus subtilis OutB, for which no enzymatic
      activities are currently known. The observed pattern of amino acid residue
      conservation and predicted secondary structures suggest that this motif may be a
      modified version of the P-loop of nucleotide binding domains, and that it is
      likely to be involved in phosphate binding. We call it PP-motif, since it appears
      to be a part of a previously uncharacterized ATP pyrophophatase domain. ATP
      sulfurylases, NtrL, and OutB consist of this domain alone. In other proteins, the
      pyrophosphatase domain is associated with amidotransferase domains (type I or
      type II), a putative citrulline-aspartate ligase domain or a nitrilase/amidase
      domain. Unexpectedly, statistically significant overall sequence similarity was
      found between ATP sulfurylase and 3'-phosphoadenosine 5'-phosphosulfate (PAPS)
      reductase, another protein of the sulfate activation pathway. The PP-motif is
      strongly modified in PAPS reductases, but they share with ATP sulfurylases
      another conserved motif which might be involved in sulfate binding. We propose
      that PAPS reductases may have evolved from ATP sulfurylases; the evolution of the
      new enzymatic function appears to be accompanied by a switch of the strongest
      functional constraint from the PP-motif to the putative sulfate-binding motif.

PMID- 7731954
TI  - A model for the structure of a homodimeric prohormone: the precursor to the
      locust neuropeptide AKH I.
AB  - We have determined the structure in solution of a homodimeric protein that is a
      precursor to the locust neuropeptide adipokinetic hormone I using nuclear
      magnetic resonance spectroscopy. This precursor, called P1, is comprised of two
      41 residue strands joined by a single inter-chain disulphide at Cys39. We have
      also determined the structure of an end product of P1 processing, called APRP1;
      this is a homodimer comprised of residues 14-41 of P1. Nuclear Overhauser Effect
      (nOe) data indicate that in both P1 and APRP1, residues 22-37 (numbered with
      respect to P1) form pairs of alpha-helices, with no evidence for any other
      secondary structure.

PMID- 7731955
TI  - Quantum mechanical model assembly study on the energetics of binding of
      arabinose, fucose, and galactose to L-arabinose-binding protein.
AB  - Binding energies of L-arabinose, D-fucose, and D-galactose to L-arabinose-binding
      protein was investigated theoretically. The calculated binding energies were
      composed of three contributions: 1) direct ligand-active site interaction
      energies calculated using static ab initio model assemblies; 2) solvation
      energies of the ligands; and 3) long-range electrostatic interaction energies
      between the ligands and the protein matrix. The calculated binding energies and
      the contributions of the energy components were used to analyze the experimental
      affinities of the ligands.

PMID- 7731956
TI  - Ethanol, gamma-aminobutyrate type A receptors, and protein kinase C
      phosphorylation.

PMID- 7731957
TI  - Simple tandem DNA repeats and human genetic disease.
AB  - The human genome contains many repeated DNA sequences that vary in complexity of
      repeating unit from a single nucleotide to a whole gene. The repeat sequences can
      be widely dispersed or in simple tandem arrays. Arrays of up to 5 or 6 nt are
      known as simple tandem repeats, and these are widely dispersed and highly
      polymorphic. Members of one group of the simple tandem repeats, the trinucleotide
      repeats, can undergo an increase in copy number by a process of dynamic mutation.
      Dynamic mutations of the CCG trinucleotide give rise to one group of fragile
      sites on human chromosomes, the rare folate-sensitive group. One member of this
      group, the fragile X (FRAXA) is responsible for the most common familial form of
      mental retardation. Another member of the group FRAXE is responsible for a rarer
      mild form of mental retardation. Similar mutations of AGC repeats give rise to a
      number of neurological disorders. The expanded repeats are unstable between
      generations and somatically. The intergenerational instability gives rise to
      unusual patterns of inheritance--particularly anticipation, the increasing
      severity and/or earlier age of onset of the disorder in successive generations.
      Dynamic mutations have been found only in the human species, and possible reasons
      for this are considered. The mechanism of dynamic mutation is discussed, and a
      number of observations of simple tandem repeat mutation that could assist in
      understanding this phenomenon are commented on.

PMID- 7731958
TI  - CC-1065 and the duocarmycins: unraveling the keys to a new class of naturally
      derived DNA alkylating agents.
AB  - Key studies defining the DNA alkylation properties and selectivity of a new class
      of exceptionally potent, naturally occurring antitumor antibiotics including CC
      1065, duocarmycin A, and duocarmycin SA are reviewed. Recent studies conducted
      with synthetic agents containing deep-seated structural changes and the unnatural
      enantiomers of the natural products and related analogs have defined the
      structural basis for the sequence-selective alkylation of duplex DNA and
      fundamental relationships between chemical structure, functional reactivity, and
      biological properties. The agents undergo a reversible, stereoelectronically
      controlled adenine-N3 addition to the least substituted carbon of the activated
      cyclopropane within selected AT-rich sites. The preferential AT-rich non-covalent
      binding selectivity of the agents within the narrower, deeper AT-rich minor
      groove and the steric accessibility to the alkylation site that accompanies deep
      AT-rich minor groove penetration control the sequence-selective DNA alkylation
      reaction and stabilize the resulting adduct. For the agents that possess
      sufficient reactivity to alkylate DNA, a direct relationship between chemical or
      functional stability and biological potency has been defined.

PMID- 7731961
TI  - Codominance and toxins: a path to drugs of nearly unlimited selectivity.
AB  - The effectiveness of drugs is often limited by their insufficient selectivity. I
      propose designs of therapeutic agents that address this problem. The key feature
      of these reagents, termed comtoxins (codominance-mediated toxins), is their
      ability to utilize codominance, a property characteristic of many signals in
      proteins, including degradation signals (degrons) and nuclear localization
      signals. A comtoxin designed to kill cells that express intracellular proteins P1
      and P2 but to spare cells that lack P1 and/or P2 is a multidomain fusion
      containing a cytotoxic domain and two degrons placed within or near two domains
      P1* and P2* that bind, respectively, to P1 and P2. In a cell containing both P1
      and P2, these proteins would bind to the P1* and P2* domains of the comtoxin and
      sterically mask the nearby (appropriately positioned) degrons, resulting in a
      long-lived and therefore toxic drug. By contrast, in a cell lacking P1 and/or P2,
      at least one of the comtoxin's degrons would be active (unobstructed), yielding a
      short-lived and therefore nontoxic drug. A comtoxin containing both a degron and
      a nuclear localization signal can be designed to kill exclusively cells that
      contain P1 but lack P2. Analogous strategies yield comtoxins sensitive to the
      presence (or absence) of more than two proteins in a cell. Also considered is a
      class of comtoxins in which a toxic domain is split by a flexible insert
      containing binding sites for the target proteins. The potentially unlimited,
      combinatorial selectivity of comtoxins may help solve the problem of side effects
      that bedevils present-day therapies, for even nonselective delivery of a comtoxin
      would not affect cells whose protein "signatures" differ from the targeted one.

PMID- 7731960
TI  - Mutant mice lacking the gamma isoform of protein kinase C show decreased
      behavioral actions of ethanol and altered function of gamma-aminobutyrate type A
      receptors.
AB  - Calcium/phospholipid-dependent protein kinase (protein kinase C, PKC) has been
      suggested to play a role in the sensitivity of gamma-aminobutyrate type A (GABAA)
      receptors to ethanol. We tested a line of null mutant mice that lacks the gamma
      isoform of PKC (PKC gamma) to determine the role of this brain-specific isoenzyme
      in ethanol sensitivity. We found that the mutation reduced the amount of PKC
      gamma immunoreactivity in cerebellum to undetectable levels without altering the
      levels of the alpha, beta I, or beta II isoforms of PKC. The mutant mice display
      reduced sensitivity to the effects of ethanol on loss of righting reflex and
      hypothermia but show normal responses to flunitrazepam or pentobarbital.
      Likewise, GABAA receptor function of isolated brain membranes showed that the
      mutation abolished the action of ethanol but did not alter actions of
      flunitrazepam or pentobarbital. These studies show the unique interactions of
      ethanol with GABAA receptors and suggest protein kinase isoenzymes as possible
      determinants of genetic differences in response to ethanol.

PMID- 7731959
TI  - Hormones and mammary carcinogenesis in mice, rats, and humans: a unifying
      hypothesis.
AB  - An attempt has been made to put forward a unifying hypothesis explaining the role
      hormones play in the genesis of mammary cancers of different phenotypes and
      genotypes in mice, rats, and humans. Most mammary cancers in these species
      originate in luminal mammary epithelial cells lining the mammary ducts and
      alveoli. These cancers are histopathologically diverse and are classified on the
      basis of growth requirements as hormone-dependent or hormone-independent tumors.
      In most strains of mice, mammary cancers at the time of detection are largely of
      the hormone-independent type; in rats, almost all mammary cancers are hormone
      dependent, while humans have both phenotypes. In spite of these differences, in
      vivo studies show that hormones (ovarian and pituitary) are essential for luminal
      mammary epithelial cell proliferation and also for the development of mammary
      cancers of both hormone-independent and hormone-dependent types. This article,
      based on our extensive in vivo and in vivo studies and on current literature,
      proposes a model to explain the central role of hormones in the genesis of all
      types of mammary cancers. The model attempts to address the following questions:
      (i) how hormones regulate luminal mammary epithelial cell proliferation, (ii) why
      hormones are required for the genesis of mammary cancers of all phenotypes and
      genotypes, including those which are always classified as hormone-independent
      tumors, and (iii) why the three species (mouse, rat, and human) have consistently
      different ratios of hormone-dependent to hormone-independent tumors.

PMID- 7731962
TI  - Use of binding energy by an RNA enzyme for catalysis by positioning and substrate
      destabilization.
AB  - A fundamental catalytic principle for protein enzymes in the use of binding
      interactions away from the site of chemical transformation for catalysis. We have
      compared the binding and reactivity of a series of oligonucleotide substrates and
      products of the Tetrahymena ribozyme, which catalyzes a site-specific
      phosphodiester cleavage reaction: CCCUCUpA+G<-->CCCUCU-OH+GpA. The results
      suggest that this RNA enzyme, like protein enzymes, can utilize binding
      interactions to achieve substantial catalysis via entropic fixation and substrate
      destabilization. The stronger binding of the all-ribose oligonucleotide product
      compared to an analog with a terminal 3' deoxyribose residue gives an effective
      concentration of 2200 M for the 3' hydroxyl group, a value approaching those
      obtained with protein enzymes and suggesting the presence of a structurally well
      defined active site capable of precise positioning. The stabilization from
      tertiary binding interactions is 40-fold less for the oligonucleotide substrate
      than the oligonucleotide product, despite the presence of the reactive phosphoryl
      group in the substrate. This destabilization is accounted for by a model in which
      tertiary interactions away from the site of bond cleavage position the electron
      deficient 3' bridging phosphoryl oxygen of the oligonucleotide substrate next to
      an electropositive Mg ion. As the phosphodiester bond breaks and this 3' oxygen
      atom develops a negative charge in the transition state, the weak interaction of
      the substrate with Mg2+ becomes strong. These strategies of "substrate
      destabilization" and "transition state stabilization" provide estimated rate
      enhancements of approximately 280- and approximately 60-fold, respectively.
      Analogous substrate destabilization by a metal ion or hydrogen bond donor may be
      used more generally by RNA and protein enzymes catalyzing reactions of phosphate
      esters.

PMID- 7731963
TI  - Disruption of the adenosine deaminase gene causes hepatocellular impairment and
      perinatal lethality in mice.
AB  - We have generated mice with a null mutation at the Ada locus, which encodes the
      purine catabolic enzyme adenosine deaminase (ADA, EC 3.5.4.4). ADA-deficient
      fetuses exhibited hepatocellular impairment and died perinatally. Their lymphoid
      tissues were not largely affected. Accumulation of ADA substrates was detectable
      in ADA-deficient conceptuses as early as 12.5 days postcoitum, dramatically
      increasing during late in utero development, and is the likely cause of liver
      damage and fetal death. The results presented here demonstrate that ADA is
      important for the homeostatic maintenance of purines in mice.

PMID- 7731964
TI  - In vivo estradiol-dependent dephosphorylation of the repressor MDBP-2-H1
      correlates with the loss of in vitro preferential binding to methylated DNA.
AB  - We have previously shown that estradiol treatment of roosters resulted in a rapid
      loss of binding activity of the repressor MDBP-2-H1 (a member of the histone H1
      family) to methylated DNA that was not due to a decrease in MDBP-2-H1
      concentration. Here we demonstrate that MDBP-2-H1 from rooster liver nuclear
      extracts is a phosphoprotein. Phosphoamino acid analysis reveals that the
      phosphorylation occurs exclusively on serine residues. Two-dimensional gel
      electrophoresis and tryptic phosphopeptide analysis show that MDBP-2-H1 is
      phosphorylated at several sites. Treatment of roosters with estradiol triggers a
      dephosphorylation of at least two sites in the protein. Phosphatase treatment of
      purified rooster MDBP-2-H1 combined with gel mobility shift assay indicates that
      phosphorylation of MDBP-2-H1 is essential for the binding to methylated DNA and
      that the dephosphorylation can occur on the protein bound to methylated DNA
      causing its release from DNA. Thus, these results suggest that in vivo
      modification of the phosphorylation status of MDBP-2-H1 caused by estradiol
      treatment may be a key step for the down regulation of its binding to methylated
      DNA.

PMID- 7731965
TI  - Folding of a nascent polypeptide chain in vitro: cooperative formation of
      structure in a protein module.
AB  - We have prepared a family of peptide fragments of the 64-residue chymotrypsin
      inhibitor 2, corresponding to its progressive elongation from the N terminus. The
      growing polypeptide chain has little tendency to form stable structure until it
      is largely synthesized, and what structures are formed are nonnative and lack, in
      particular, the native secondary structural elements of alpha-helix and beta
      sheet. These elements then develop as sufficient tertiary interactions are made
      in the nearly full-length chain. The growth of structure in the small module is
      highly cooperative and does not result from the hierarchical accretion of
      substructures.

PMID- 7731966
TI  - Analysis of the mouse Splotch-delayed mutation indicates that the Pax-3 paired
      domain can influence homeodomain DNA-binding activity.
AB  - The murine Pax-3 protein contains two DNA-binding domains, a paired domain and a
      homeodomain, and alterations in the Pax-3 gene are responsible for the neural
      tube defects observed in the Splotch (Sp) mouse mutant. Of five Sp alleles,
      Splotch-delayed (Spd) is the only one that encodes a full-length Pax-3 protein,
      containing a single glycine-to-arginine substitution within the paired domain. To
      better understand the consequence of this mutation on Pax-3 function, we have
      analyzed the DNA-binding properties of wild-type and Spd Pax-3, using
      oligonucleotides that bind primarily to the paired domain (e5) or exclusively to
      the homeodomain (P2). Wild-type Pax-3 was found to bind e5 in a specific manner.
      In contrast, the Spd mutation reduced binding of Pax-3 to e5 17-fold, revealing a
      defect in DNA binding by the paired domain. Surprisingly, the Spd mutation also
      drastically reduced the homeodomain-specific binding to P2 by 21-fold when
      compared with the wild-type protein. Interestingly, a deletion which removes the
      Spd mutation was found to restore P2-binding activity, suggesting that within the
      full-length Pax-3 protein, the paired domain and homeodomain may interact. We
      conclude, therefore, that the Spd mutation is phenotyically expressed in vitro by
      a defect in the DNA-binding properties of Pax-3. Furthermore, it is apparent that
      the paired domain and homeodomain of Pax-3 do not function as independent
      domains, since a mutation in the former impairs the DNA-binding activity of the
      latter.

PMID- 7731967
TI  - G-utrophin, the autosomal homologue of dystrophin Dp116, is expressed in sensory
      ganglia and brain.
AB  - The utrophin gene is closely related to the dystrophin gene in both sequence and
      genomic structure. The Duchenne muscular dystrophy (DMD) locus encodes three 14
      kb dystrophin transcripts in addition to several smaller isoforms, one of which,
      Dp116, is specific to peripheral nerve. We describe here the corresponding 5.5-kb
      mRNA from the utrophin locus. This transcript, designated G-utrophin, is of
      particular interest because it is specifically expressed in the adult mouse brain
      and appears to be the predominant utrophin transcript in this tissue. G-utrophin
      is expressed in brain sites generally different from the regions expressing beta
      dystroglycan. During mouse embryogenesis G-utrophin is also seen in the
      developing sensory ganglia. Our data confirm the close evolutionary relationships
      between the DMD and utrophin loci; however, the functions for the corresponding
      proteins probably differ.

PMID- 7731968
TI  - Expressed cadherin pseudogenes are localized to the critical region of the spinal
      muscular atrophy gene.
AB  - Low-copy repeats have been associated with genomic rearrangements and have been
      implicated in the generation of mutations in several diseases. Here we
      characterize a subset of low-copy repeats in the spinal muscular atrophy (SMA)
      region in human chromosome 5q13. We show that this repeated sequence, named c41
      cad, is a highly expressed pseudogene derived from an intact neuronal cadherin
      gene, Br-cadherin, situated on 5p13-14. Br-cadherin is expressed specifically in
      the brain, whereas the c41-cad transcripts are 10-15 times more abundant and are
      present in all tissues examined. We speculate that the c41-cad repeats,
      separately or in concert with other repeats in the SMA region, are involved in
      the pathogenesis of SMA by promoting rearrangements and deletions.

PMID- 7731969
TI  - In vivo estimates of division and death rates of human T lymphocytes.
AB  - We present data on the decay, after radiotherapy, of naive and memory human T
      lymphocytes with stable chromosome damage. These data are analyzed in conjunction
      with existing data on the decay of naive and memory T lymphocytes with unstable
      chromosome damage and older data on unsorted lymphocytes. The analyses yield in
      vivo estimates for some life-history parameters of human T lymphocytes. Best
      estimates of proliferation rates have naive lymphocytes dividing once every 3.5
      years and memory lymphocytes dividing once every 22 weeks. It appears that memory
      lymphocytes can revert to the naive phenotype, but only, on average, after 3.5
      years in the memory class. The lymphocytes with stable chromosome damage decay
      very slowly, yielding surprisingly low estimates of their death rate. The
      estimated parameters are used in a simple mathematical model of the population
      dynamics of undamaged naive and memory lymphocytes. We use this model to
      illustrate that it is possible for the unprimed subset of a constantly stimulated
      clone to stay small, even when there is a large population of specific primed
      cells reverting to the unprimed state.

PMID- 7731970
TI  - Regulation of T-cell antigen receptor (TCR) alpha-chain expression by TCR beta
      chain transcripts.
AB  - The TCR is an alpha beta heterodimer, a part of the multimeric structure through
      which physiological T-cell activation occurs. The expression of TCR alpha chain
      is greatly diminished in a beta-chain-deficient mutant Jurkat cell line (J.RT3
      T3.5). The relationship between the expression of the TCR alpha and beta chains
      has been examined by stable transfection of a series of TCR beta-chain mutant
      constructs into this mutant cell line. The level of alpha-chain transcript was
      dramatically upregulated by the expression of the beta chain and specifically by
      a transcript of the beta-chain variable region alone, including a transcript in
      which the ATG start codon was mutated. The downregulation of the endogenous alpha
      chain transcripts in mutants cells lacking complete beta-chain transcripts
      occurred primarily at the posttranscriptional level. This evidence for a
      regulatory function of the TCR beta-chain gene represents an unusual regulatory
      pathway in which the transcript of one gene is required for the optimal
      expression of another gene.

PMID- 7731971
TI  - Localization of specific erythropoietin binding sites in defined areas of the
      mouse brain.
AB  - The main physiological regulator of erythropoiesis is the hematopoietic growth
      factor erythropoietin (EPO), which is induced in response to hypoxia. Binding of
      EPO to the EPO receptor (EPO-R), a member of the cytokine receptor superfamily,
      controls the terminal maturation of red blood cells. So far, EPO has been
      reported to act mainly on erythroid precursor cells. However, we have detected
      mRNA encoding both EPO and EPO-R in mouse brain by reverse transcription-PCR.
      Exposure to 0.1% carbon monoxide, a procedure that causes functional anemia,
      resulted in a 20-fold increase of EPO mRNA in mouse brain as quantified by
      competitive reverse transcription-PCR, whereas the EPO-R mRNA level was not
      influenced by hypoxia. Binding studies on mouse brain sections revealed defined
      binding sites for radioiodinated EPO in distinct brain areas. The specificity of
      EPO binding was assessed by homologous competition with an excess of unlabeled
      EPO and by using two monoclonal antibodies against human EPO, one inhibitory and
      the other noninhibitory for binding of EPO to EPO-R. Major EPO binding sites were
      observed in the hippocampus, capsula interna, cortex, and midbrain areas.
      Functional expression of the EPO-R and hypoxic upregulation of EPO suggest a role
      of EPO in the brain.

PMID- 7731972
TI  - Distinct neural correlates of visual long-term memory for spatial location and
      object identity: a positron emission tomography study in humans.
AB  - The purpose of the present study was to investigate by using positron emission
      tomography (PET) whether the cortical pathways that are involved in visual
      perception of spatial location and object identity are also differentially
      implicated in retrieval of these types of information from episodic long-term
      memory. Subjects studied a set of displays consisting of three unique
      representational line drawings arranged in different spatial configurations.
      Later, while undergoing PET scanning, subjects' memory for spatial location and
      identity of the objects in the displays was tested and compared to a perceptual
      baseline task involving the same displays. In comparison to the baseline task,
      each of the memory tasks activated both the dorsal and the ventral pathways in
      the right hemisphere but not to an equal extent. There was also activation of the
      right prefrontal cortex. When PET scans of the memory tasks were compared to each
      other, areas of activation were very circumscribed and restricted to the right
      hemisphere: For retrieval of object identity, the area was in the inferior
      temporal cortex in the region of the fusiform gyrus (area 37), whereas for
      retrieval of spatial location, it was in the inferior parietal lobule in the
      region of the supramarginal gyrus (area 40). Thus, our study shows that distinct
      neural pathways are activated during retrieval of information about spatial
      location and object identity from long-term memory.

PMID- 7731973
TI  - Molecular and cytotoxic effects of camptothecin, a topoisomerase I inhibitor, on
      trypanosomes and Leishmania.
AB  - Parasites pose a threat to the health and lives of many millions of human beings.
      Among the pathogenic protozoa, Trypanosoma brucei, Trypanosoma cruzi, and
      Leishmania donovani are hemoflagellates that cause particularly serious diseases
      (sleeping sickness, Chagas disease, and leishmaniasis, respectively). The drugs
      currently available to treat these infections are limited by marginal efficacy,
      severe toxicity, and spreading drug resistance. Camptothecin is an established
      antitumor drug and a well-characterized inhibitor of eukaryotic DNA topoisomerase
      I. When trypanosomes or leishmania are treated with camptothecin and then lysed
      with SDS, both nuclear and mitochondrial DNA are cleaved and covalently linked to
      protein. This is consistent with the existence of drug-sensitive topoisomerase I
      activity in both compartments. Camptothecin also inhibits the incorporation of
      [3H]thymidine in these parasites. These molecular effects are cytotoxic to cells
      in vitro, with EC50 values for T. brucei, T. cruzi, and L. donovani, of 1.5, 1.6,
      and 3.2 microM, respectively. For these parasites, camptothecin is an important
      lead for much-needed new chemotherapy, as well as a valuable tool for studying
      topoisomerase I activity.

PMID- 7731974
TI  - Trans-Pacific migrations of the loggerhead turtle (Caretta caretta) demonstrated
      with mitochondrial DNA markers.
AB  - Juvenile loggerhead turtles (Caretta caretta) have recently been documented in
      the vicinity of Baja California and thousands of these animals have been captured
      in oceanic fisheries of the North Pacific. The presence of loggerhead turtles in
      the central and eastern North Pacific is a prominent enigma in marine turtle
      distribution because the nearest documented nesting concentrations for this
      species are in Australia and Japan, over 10,000 km from Baja California. To
      determine the origin of the Baja California feeding aggregate and North Pacific
      fishery mortalities, samples from nesting areas and pelagic feeding aggregates
      were compared with genetic markers derived from mtDNA control region sequences.
      Overall, 57 of 60 pelagic samples (95%) match haplotypes seen only in Japanese
      nesting areas, implicating Japan as the primary source of turtles in the North
      Pacific Current and around Baja California. Australian nesting colonies may
      contribute the remaining 5% of these pelagic feeding aggregates. Juvenile
      loggerhead turtles apparently traverse the entire Pacific Ocean, approximately
      one-third of the planet, in the course of developmental migrations, but mortality
      in high-seas fisheries raises concern over the future of this migratory
      population.

PMID- 7731975
TI  - Diminished degradation of yeast cytochrome c by interactions with its
      physiological partners.
AB  - The level and structure of yeast iso-1-cytochrome c and iso-2-cytochrome c,
      encoded by the nuclear genes CYC1 and CYC7, respectively, are normally not
      altered in rho- mutants, which completely lack the cytochromes a.a3 subunits and
      cytochrome b that are encoded by mitochondrial DNA. In contrast, iso-cytochromes
      c containing the amino acid change Thr-78-->Ile (T78I) were observed at the
      normal or near-normal wild-type level in rho+ strains but were completely absent
      in rho- mutants. We have demonstrated with the "global" suppressor mutation Asn
      52-->Ile and by pulse-chase labeling that the T78I iso-1-cytochrome c undergoes
      rapid cellular degradation in rho- mutants. Furthermore, specific mutations
      revealed that the deficiency of T78I iso-1 cytochrome c can be caused by the lack
      of cytochrome a.a3 or cytochrome c1, but not by the lack of cytochrome b. Thus,
      this and certain other, but not all, labile forms of cytochrome c are protected
      from degradation by the interaction with its physiological partners.

PMID- 7731976
TI  - Rectification and signal averaging of weak electric fields by biological cells.
AB  - Oscillating electric fields can be rectified by proteins in cell membranes to
      give rise to a dc transport of a substance across the membrane or a net
      conversion of a substrate to a product. This provides a basis for signal
      averaging and may be important for understanding the effects of weak extremely
      low frequency (ELF) electric fields on cellular systems. We consider the limits
      imposed by thermal and "excess" biological noise on the magnitude and exposure
      duration of such electric field-induced membrane activity. Under certain
      circumstances, the excess noise leads to an increase in the signal-to-noise ratio
      in a manner similar to processes labeled "stochastic resonance." Numerical
      results indicate that it is difficult to reconcile biological effects with low
      field strengths.

PMID- 7731977
TI  - Neurotoxicity of advanced glycation endproducts during focal stroke and
      neuroprotective effects of aminoguanidine.
AB  - Cerebral infarction (stroke) is a potentially disastrous complication of diabetes
      mellitus, principally because the extent of cortical loss is greater in diabetic
      patients than in nondiabetic patients. The etiology of this enhanced
      neurotoxicity is poorly understood. We hypothesized that advanced glycation
      endproducts (AGEs), which have previously been implicated in the development of
      other diabetic complications, might contribute to neurotoxicity and brain damage
      during ischemic stroke. Using a rat model of focal cerebral ischemia, we show
      that systemically administered AGE-modified bovine serum albumin (AGE-BSA)
      significantly increased cerebral infarct size. The neurotoxic effects of AGE-BSA
      administration were dose- and time-related and associated with a paradoxical
      increase in cerebral blood flow. Aminoguanidine, an inhibitor of AGE cross
      linking, attenuated infarct volume in AGE-treated animals. We conclude that AGEs
      may contribute to the increased severity of stroke associated with diabetes and
      other conditions characterized by AGE accumulation.

PMID- 7731978
TI  - A prokaryotic origin for light-dependent chlorophyll biosynthesis of plants.
AB  - Flowering plants require light for chlorophyll synthesis. Early studies indicated
      that the dependence on light for greening stemmed in part from the light
      dependent reduction of the chlorophyll intermediate protochlorophyllide to the
      product chlorophyllide. Light-dependent reduction of protochlorophyllide by
      flowering plants is contrasted by the ability of nonflowering plants, algae, and
      photosynthetic bacteria to reduce protochlorophyllide and, hence, synthesize
      (bacterio) chlorophyll in the dark. In this report, we functionally complemented
      a light-independent protochlorophyllide reductase mutant of the eubacterium
      Rhodobacter capsulatus with an expression library composed of genomic DNA from
      the cyanobacterium Synechocystis sp. PCC 6803. The complemented R. capsulatus
      strain is capable of synthesizing bacteriochlorophyll in the light, thereby
      indicating that a chlorophyll biosynthesis enzyme can function in the
      bacteriochlorophyll biosynthetic pathway. However, under dark growth conditions
      the complemented R. capsulatus strain fails to synthesize bacteriochlorophyll and
      instead accumulates protochlorophyllide. Sequence analysis demonstrates that the
      complementing Synechocystis genomic DNA fragment exhibits a high degree of
      sequence identity (53-56%) with light-dependent protochlorophyllide reductase
      enzymes found in plants. The observation that a plant-type, light-dependent
      protochlorophyllide reductase enzyme exists in a cyanobacterium indicates that
      light-dependent protochlorophyllide reductase evolved before the advent of
      eukaryotic photosynthesis. As such, this enzyme did not arise to fulfill a
      function necessitated either by the endosymbiotic evolution of the chloroplast or
      by multicellularity; rather, it evolved to fulfill a fundamentally cell
      autonomous role.

PMID- 7731979
TI  - Oxygen as a key developmental regulator of Rhizobium meliloti N2-fixation gene
      expression within the alfalfa root nodule.
AB  - The symbiotic pattern of expression of Rhizobium meliloti N2-fixation genes is
      tightly coupled with the histological organization of the alfalfa root nodule and
      thus is under developmental control. N2-fixation gene expression is induced very
      sharply at a particular zone of the nodule called interzone II-III that precedes
      the zone where N2 fixation takes place. We show here that this coupling can be
      disrupted, hereby resulting in ectopic expression of N2-fixation genes in the
      prefixing zone II of the nodule. Uncoupling was obtained either by using a R.
      meliloti strain in which a mutation rendered N2-fixation gene expression
      constitutive with respect to oxygen in free-living bacterial cultures or by
      placing nodules induced by a wild-type R. meliloti strain in a microoxic
      environment. These results implicate oxygen as a key determinant of the symbiotic
      pattern of N2-fixation gene expression.

PMID- 7731980
TI  - Inactivation of ethanol-inducible cytochrome P450 and other microsomal P450
      isozymes by trans-4-hydroxy-2-nonenal, a major product of membrane lipid
      peroxidation.
AB  - Of the microsomal P450 cytochromes, the ethanol-inducible isoform, P450 2E1, is
      believed to be predominant in leading to oxidative damage, including the
      generation of radical species that contribute to lipid peroxidation, and in the
      reductive beta-scission of lipid hydroperoxides to give hydrocarbons and
      aldehydes. In the present study, the sensitivity of a series of P450s to trans-4
      hydroxy-2-nonenal (HNE), a known toxic product of membrane lipid peroxidation,
      was determined. After incubation of a purified cytochrome with HNE, the other
      components of the reconstituted system (NADPH-cytochrome P450 reductase,
      phosphatidylcholine, and NADPH) were added, and the rate of oxygenation of 1
      phenylethanol to yield acetophenone was assayed. Inactivation occurs in a time
      dependent and HNE concentration-dependent manner, with P450s 2E1 and 1A1 being
      the most sensitive, followed by isoforms 1A2, 3A6, and 2B4. At an HNE
      concentration of 0.24 microM, which was close to the micromolar concentration of
      the enzyme, four of the isoforms were significantly inhibited, but not P450 2B4.
      In other experiments, the reductase was shown to be only relatively weakly
      inactivated by HNE. P450s 2E1 and 2B4 in microsomal membranes from animals
      induced with acetone or phenobarbital, respectively, are as readily inhibited as
      the purified forms. Evidence was obtained that the P450 heme is apparently not
      altered and the sulfur ligand is not displaced, that substrate protects against
      HNE, and that the inactivation is reversed upon dialysis. Higher levels of
      reductase or substrate do not restore the activity of inhibited P450 in the
      catalytic assay. Our results suggest that the observed inhibition of the various
      P450s is of sufficient magnitude to cause significant changes in the metabolism
      of foreign compounds such as drugs and chemical carcinogens by the P450 oxygenase
      system at HNE concentrations that occur in biological membranes. In view of the
      known activities of P450 2E1 in generating lipid hydroperoxides and in their beta
      scission, its inhibition by this product of membrane peroxidation may provide a
      negative regulatory function.

PMID- 7731981
TI  - A progesterone metabolite stimulates the release of gonadotropin-releasing
      hormone from GT1-1 hypothalamic neurons via the gamma-aminobutyric acid type A
      receptor.
AB  - The reduced progesterone metabolite tetrahydroprogesterone (3 alpha-hydroxy-5
      alpha-pregnan-20-one; 3 alpha,5 alpha-THP) is a positive modulator of the gamma
      aminobutyric acid type A (GABAA) receptor. Experiments performed in vitro with
      hypothalamic fragments have previously shown that GABA could modulate the release
      of gonadotropin-releasing hormone (GnRH). Using GT1-1 immortalized GnRH neurons,
      we investigated the role of GABAA receptor ligands, including 3 alpha,5 alpha
      THP, on the release of GnRH. We first characterized the GABAA receptors expressed
      by these neurons. [3H]Muscimol, but not [3H]flunitrazepam, bound with high
      affinity to GT1-1 cell membranes (Kd = 10.9 +/- 0.3 nM; Bmax = 979 +/- 12 fmol/mg
      of protein), and [3H]muscimol binding was enhanced by 3 alpha,5 alpha-THP. mRNAs
      encoding the alpha 1 and beta 3 subunits of the GABAA receptor were detected by
      the reverse transcriptase polymerase chain reaction. In agreement with binding
      data, the benzodiazepine-binding gamma subunit mRNA was absent. GnRH release
      studies showed a dose-related stimulating action of muscimol. 3 alpha,5 alpha-THP
      not only modulated muscimol-induced secretion but also stimulated GnRH release
      when administered alone. Bicuculline and picrotoxin blocked the effects of 3
      alpha,5 alpha-THP and muscimol. Finally, we observed that GT1-1 neurons convert
      progesterone to 3 alpha,5 alpha-THP. We propose that progesterone may increase
      the release of GnRH by a membrane mechanism, via its reduced metabolite 3 alpha,5
      alpha-THP acting at the GABAA receptor.

PMID- 7731982
TI  - Neurosteroids, via sigma receptors, modulate the [3H]norepinephrine release
      evoked by N-methyl-D-aspartate in the rat hippocampus.
AB  - N-Methyl-D-aspartate (NMDA, 200 microM) evokes the release of [3H]norepinephrine
      ([3H]NE) from preloaded hippocampal slices. This effect is potentiated by
      dehydroepiandrosterone sulfate (DHEA S), whereas it is inhibited by pregnenolone
      sulfate (PREG S) and the high-affinity sigma inverse agonist 1,3-di(2
      tolyl)guanidine, at concentrations of > or = 100 nM. Neither 3 alpha-hydroxy-5
      alpha-pregnan-20-one nor its sulfate ester modified NMDA-evoked [3H]NE overflow.
      The sigma antagonists haloperidol and 1-[2-(3,4-dichlorophenyl)-ethyl]-4
      methylpiperazine, although inactive by themselves, completely prevented the
      effects of DHEA S, PREG S, and 1,3-di(2-tolyl)guanidine on NMDA-evoked [3H]NE
      release. Progesterone (100 nM) mimicked the antagonistic effect of haloperidol
      and 1-[2-(3,4-dichlorophenyl)ethyl]-4-methyl-piperazine. These results indicate
      that the tested steroid sulfate esters differentially affected the NMDA response
      in vitro and suggest that DHEA S acts as a sigma agonist, that PREG S acts as a
      sigma inverse agonist, and that progesterone may act as a sigma antagonist.
      Pertussis toxin, which inactivates the Gi/o types of guanine nucleotide-binding
      protein (Gi/o protein) function, suppresses both effects of DHEA S and PREG S.
      Since sigma 1 but not sigma 2 receptors are coupled to Gi/o proteins, the present
      results suggest that DHEA S and PREG S control the NMDA response via sigma 1
      receptors.

PMID- 7731983
TI  - The ATX1 gene of Saccharomyces cerevisiae encodes a small metal homeostasis
      factor that protects cells against reactive oxygen toxicity.
AB  - In aerobic organisms, protection against oxidative damage involves the combined
      action of highly specialized antioxidant enzymes, such as superoxide dismutase
      (SOD) and catalase. Here we describe the isolation and characterization of
      another gene in the yeast Saccharomyces cerevisiae that plays a critical role in
      detoxification of reactive oxygen species. This gene, named ATX1, was originally
      isolated by its ability to suppress oxygen toxicity in yeast lacking SOD. ATX1
      encodes a 8.2-kDa polypeptide exhibiting significant similarity and identity to
      various bacterial metal transporters. Potential ATX1 homologues were also
      identified in multicellular eukaryotes, including the plants Arabidopsis thaliana
      and Oryza sativa and the nematode Caenorhabditis elegans. In yeast cells, ATX1
      evidently acts in the transport and/or partitioning of copper, and this role in
      copper homeostasis appears to be directly relevant to the ATX1 suppression of
      oxygen toxicity: ATX1 was incapable of compensating for SOD when cells were
      depleted of exogenous copper. Strains containing a deletion in the chromosomal
      ATX1 locus were generated. Loss of ATX1 function rendered both mutant and wild
      type SOD strains hypersensitive toward paraquat (a generator of superoxide anion)
      and was also associated with an increased sensitivity toward hydrogen peroxide.
      Hence, ATX1 protects cells against the toxicity of both superoxide anion and
      hydrogen peroxide.

PMID- 7731984
TI  - A chloroplast homologue of the signal recognition particle subunit SRP54 is
      involved in the posttranslational integration of a protein into thylakoid
      membranes.
AB  - The mechanisms involved in the integration of proteins into the thylakoid
      membrane are largely unknown. However, many of the steps of this process for the
      light-harvesting chlorophyll a/b protein (LHCP) have been described and
      reconstituted in vitro. LHCP is synthesized as a precursor in the cytosol and
      posttranslationally imported into chloroplasts. Upon translocation across the
      envelope membranes, the N-terminal transit peptide is cleaved, and the apoprotein
      is assembled into a soluble "transit complex" and then integrated into the
      thylakoid membrane via three transmembrane helices. Here we show that 54CP, a
      chloroplast homologue of the 54-kDa subunit of the mammalian signal recognition
      particle (SRP54), is essential for transit complex formation, is present in the
      complex, and is required for LHCP integration into the thylakoid membrane. Our
      data indicate that 54CP functions posttranslationally as a molecular chaperone
      and potentially pilots LHCP to the thylakoids. These results demonstrate that one
      of several pathways for protein routing to the thylakoids is homologous to the
      SRP pathway and point to a common evolutionary origin for the protein transport
      systems of the endoplasmic reticulum and the thylakoid membrane.

PMID- 7731985
TI  - Mutagenesis of the putative alpha-helical domain of the Vpr protein of human
      immunodeficiency virus type 1: effect on stability and virion incorporation.
AB  - vpr is one of the auxiliary genes of human immunodeficiency virus type 1 (HIV-1)
      and is conserved in the related HIV-2/simian immunodeficiency virus lentiviruses.
      The unique feature of Vpr is that it is the only nonstructural protein
      incorporated into the virus particle. Secondary structural analysis predicted an
      amphipathic alpha-helical domain in the amino terminus of Vpr (residues 17-34)
      which contains five acidic and four leucine residues. To evaluate the role of
      specific residues of the helical domain for virion incorporation, mutagenesis of
      this domain was carried out. Substitution of proline for any of the individual
      acidic residues (Asp-17 and Glu-21, -24, -25, and -29) eliminated the virion
      incorporation of Vpr and also altered the stability of Vpr in cells. Conservative
      replacement of glutamic residues of the helical domain with aspartic residues
      resulted in Vpr characteristic of wild type both in stability and virion
      incorporation, as did substitution of glutamine for the acidic residues. In
      contrast, replacement of leucine residues of the helical domain (residues 20, 22,
      23, and 26) by alanine eliminated virion incorporation function of Vpr. These
      data indicate that acidic and hydrophobic residues and the helical structure in
      this region are critical for the stability of Vpr and its efficient incorporation
      into virus-like particles.

PMID- 7731986
TI  - Swapping structural determinants of ribonucleases: an energetic analysis of the
      hinge peptide 16-22.
AB  - Bovine seminal ribonuclease (BS-RNase) is a homodimeric enzyme strictly
      homologous to the pancreatic ribonuclease (RNase A). Native BS-RNase is an
      equilibrium mixture of two distinct dimers differing in the interchange of the N
      terminal segments and in their biological properties. The loop 16-22 plays a
      fundamental role on the relative stability of the two isomers. Both the primary
      and tertiary structures of the RNase A differ substantially from those of the
      seminal ribonuclease in the loop region 16-22. To analyze the possible stable
      conformations of this loop in both enzymes, structure predictions have been
      attempted, according to a procedure described by Palmer and Scheraga [Palmer, K.
      A. & Scheraga, H. A. (1992) J. Comput. Chem. 13, 329-350]. Results compare well
      with experimental x-ray structures and clarify the structural determinants that
      are responsible for the swapping of the N-terminal domains and for the peculiar
      properties of BS-RNase. Minimal modifications of RNase A sequence needed to form
      a stable swapped dimer are also predicted.

PMID- 7731987
TI  - Transposable elements are stable structural components of Drosophila melanogaster
      heterochromatin.
AB  - We determined the distribution of 11 different transposable elements on
      Drosophila melanogaster mitotic chromosomes by using high-resolution fluorescent
      in situ hybridization (FISH) coupled with charge-coupled device camera analysis.
      Nine of these transposable elements (copia, gypsy, mdg-1, blood, Doc, I, F, G,
      and Bari-1) are preferentially clustered into one or more discrete
      heterochromatic regions in chromosomes of the Oregon-R laboratory stock.
      Moreover, FISH analysis of geographically distant strains revealed that the
      locations of these heterochromatic transposable element clusters are highly
      conserved. The P and hobo elements, which are likely to have invaded the D.
      melanogaster genome at the beginning of this century, are absent from Oregon-R
      heterochromatin but clearly exhibit heterochromatic clusters in certain natural
      populations. Together these data indicate that transposable elements are major
      structural components of Drosophila heterochromatin, and they change the current
      views on the role of transposable elements in host genome evolution.

PMID- 7731988
TI  - The nucleotide sequence of chromosome I from Saccharomyces cerevisiae.
AB  - Chromosome I from the yeast Saccharomyces cerevisiae contains a DNA molecule of
      approximately 231 kbp and is the smallest naturally occurring functional
      eukaryotic nuclear chromosome so far characterized. The nucleotide sequence of
      this chromosome has been determined as part of an international collaboration to
      sequence the entire yeast genome. The chromosome contains 89 open reading frames
      and 4 tRNA genes. The central 165 kbp of the chromosome resembles other large
      sequenced regions of the yeast genome in both its high density and distribution
      of genes. In contrast, the remaining sequences flanking this DNA that comprise
      the two ends of the chromosome and make up more than 25% of the DNA molecule have
      a much lower gene density, are largely not transcribed, contain no genes
      essential for vegetative growth, and contain several apparent pseudogenes and a
      15-kbp redundant sequence. These terminally repetitive regions consist of a
      telomeric repeat called W', flanked by DNA closely related to the yeast FLO1
      gene. The low gene density, presence of pseudogenes, and lack of expression are
      consistent with the idea that these terminal regions represent the yeast
      equivalent of heterochromatin. The occurrence of such a high proportion of DNA
      with so little information suggests that its presence gives this chromosome the
      critical length required for proper function.

PMID- 7731989
TI  - In situ isolation of mRNA from individual plant cells: creation of cell-specific
      cDNA libraries.
AB  - A method for isolating and cloning mRNA populations from individual cells in
      living, intact plant tissues is described. The contents of individual cells were
      aspirated into micropipette tips filled with RNA extraction buffer. The mRNA from
      these cells was purified by binding to oligo(dT)-linked magnetic beads and
      amplified on the beads using reverse transcription and PCR. The cell-specific
      nature of the isolated mRNA was verified by creating cDNA libraries from
      individual tomato leaf epidermal and guard cell mRNA preparations. In testing the
      reproducibility of the method, we discovered an inherent limitation of PCR
      amplification from small amounts of any complex template. This phenomenon, which
      we have termed the "Monte Carlo" effect, is created by small and random
      differences in amplification efficiency between individual templates in an
      amplifying cDNA population. The Monte Carlo effect is dependent upon template
      concentration: the lower the abundance of any template, the less likely its true
      abundance will be reflected in the amplified library. Quantitative assessment of
      the Monte Carlo effect revealed that only rare mRNAs (< or = 0.04% of
      polyadenylylated mRNA) exhibited significant variation in amplification at the
      single-cell level. The cDNA cloning approach we describe should be useful for a
      broad range of cell-specific biological applications.

PMID- 7731990
TI  - The hepatitis B virus X protein targets the basic region-leucine zipper domain of
      CREB.
AB  - The X gene product encoded by the hepatitis B virus, termed pX, is a promiscuous
      transactivator of a variety of viral and cellular genes under the control of
      diverse cis-acting elements. Although pX does not appear to directly bind DNA, pX
      responsive elements include the NF-kappa B, AP-1, and CRE (cAMP response element)
      sites. Direct protein-protein interactions occur between viral pX and the CRE
      binding transcription factors CREB and ATF. Here we examine the mechanism of the
      protein-protein interactions occurring between CREB and pX by using recombinant
      proteins and in vitro DNA-binding assays. We demonstrate that pX interacts with
      the basic region-leucine zipper domain of CREB but not with the DNA-binding
      domain of the yeast transactivator protein Gal4. The interaction between CREB and
      pX increases the affinity of CREB for the CRE site by an order of magnitude,
      although pX does not alter the rate of CREB dimerization. Methylation
      interference footprinting reveals differences between the CREB DNA and CREB-pX
      DNA complexes. These experiments demonstrate that pX titers the way CREB
      interacts with the CRE DNA and suggest that the basic, DNA-binding region of CREB
      is the target of pX. Transfection assays in PC12 cells with the CREB-dependent
      somatostatin promoter demonstrate a nearly 15-fold transcriptional induction
      after forskolin stimulation in the presence of pX. These results support the
      significance of the CREB-pX protein-protein interactions in vivo.

PMID- 7731991
TI  - Folate receptors targeted to clathrin-coated pits cannot regulate vitamin uptake.
AB  - Potocytosis is an endocytic process that is specialized for the internalization
      of small molecules. Recent studies on the uptake of 5-methyltetrahydrofolate by
      the folate receptor have suggested that the glycosyl-phosphatidylinositol anchor
      on this protein causes it to cluster and be internalized by caveolae instead of
      coated pits. To test this hypothesis directly, we have constructed a chimeric
      folate receptor that has the glycosyl-phosphatidylinositol anchor replaced with
      the transmembrane domain and cytoplasmic tail of the low density lipoprotein
      receptor. The cells with wild-type receptors delivered 5-methyltetrahydrofolate
      to the cytoplasm more rapidly than did cells expressing the chimeric receptor.
      This suggests that efficient delivery to the cytoplasm depends on caveolae. In
      sharp contrast to cells with wild-type folate receptors, cells internalizing
      folate by clathrin-coated pits were unable to decrease vitamin uptake when they
      were either folate replete or confluent.

PMID- 7731992
TI  - Invariance and restriction toward a limited set of self-antigens characterize
      neonatal IgM antibody repertoires and prevail in autoreactive repertoires of
      healthy adults.
AB  - Analysis of the reactivity of IgM with self-antigens in tissues by a quantitative
      immunoblotting technique showed striking invariance among newborns in the human
      and in the mouse. The self-reactive repertoire of IgM of adults was also markedly
      conserved; it comprised most anti-self reactivities that prevailed among
      neonates. Multivariate analysis confirmed the homogeneity of IgM repertoires of
      neonates toward self- and non-self-antigens. Multivariate analysis discriminated
      between newborn and adult repertoires for reactivity with two of five sources of
      self-proteins and with non-self-antigens. Our observations support the concept
      that naturally activated B lymphocytes are selected early in development and
      throughout life for reactivity with a restricted set of self-antigens.

PMID- 7731993
TI  - Theory of orientation tuning in visual cortex.
AB  - The role of intrinsic cortical connections in processing sensory input and in
      generating behavioral output is poorly understood. We have examined this issue in
      the context of the tuning of neuronal responses in cortex to the orientation of a
      visual stimulus. We analytically study a simple network model that incorporates
      both orientation-selective input from the lateral geniculate nucleus and
      orientation-specific cortical interactions. Depending on the model parameters,
      the network exhibits orientation selectivity that originates from within the
      cortex, by a symmetry-breaking mechanism. In this case, the width of the
      orientation tuning can be sharp even if the lateral geniculate nucleus inputs are
      only weakly anisotropic. By using our model, several experimental consequences of
      this cortical mechanism of orientation tuning are derived. The tuning width is
      relatively independent of the contrast and angular anisotropy of the visual
      stimulus. The transient population response to changing of the stimulus
      orientation exhibits a slow "virtual rotation." Neuronal cross-correlations
      exhibit long time tails, the sign of which depends on the preferred orientations
      of the cells and the stimulus orientation.

PMID- 7731995
TI  - Rescue, propagation, and partial purification of a helper virus-dependent
      adenovirus vector.
AB  - Adenoviral vectors are widely used as highly efficient gene transfer vehicles in
      a variety of biological research strategies including human gene therapy. One of
      the limitations of the currently available adenoviral vector system is the
      presence of the majority of the viral genome in the vector, resulting in leaky
      expression of viral genes particularly at high multiplicity of infection and
      limited cloning capacity of exogenous sequences. As a first step to overcome this
      problem, we attempted to rescue a defective human adenovirus serotype 5 DNA,
      which had an essential region of the viral genome (L1, L2, VAI + II, pTP) deleted
      and replaced with an indicator gene. In the presence of wild-type adenovirus as a
      helper, this DNA was packaged and propagated as transducing viral particles.
      After several rounds of amplification, the titer of the recombinant virus reached
      at least 4 x 10(6) transducing particles per ml. The recombinant virus could be
      partially purified from the helper virus by CsCl equilibrium density-gradient
      centrifugation. The structure of the recombinant virus around the marker gene
      remained intact after serial propagation, while the pBR sequence inserted in the
      E1 region was deleted from the recombinant virus. Our results suggest that it
      should be possible to develop a helper-dependent adenoviral vector, which does
      not encode any viral proteins, as an alternative to the currently available
      adenoviral vector systems.

PMID- 7731994
TI  - Pericellular mobilization of the tissue-destructive cysteine proteinases,
      cathepsins B, L, and S, by human monocyte-derived macrophages.
AB  - Human macrophages are believed to damage host tissues in chronic inflammatory
      disease states, but these cells have been reported to express only modest
      degradative activity in vitro. However, while examining the ability of human
      monocytes to degrade the extracellular matrix component elastin, we identified
      culture conditions under which the cells matured into a macrophage population
      that displayed a degradative phenotype hundreds of times more destructive than
      that previously ascribed to any other cell population. The monocyte-derived
      macrophages synthesized elastinolytic matrix metalloproteinases (i.e., gelatinase
      B and matrilysin) as well as cysteine proteinases (i.e., cathepsins B, L, and S),
      but only the cathepsins were detected in the extracellular milieu as fully
      processed, mature enzymes by either vital fluorescence or active-site labeling.
      Consistent with these observations, macrophage-mediated elastinolytic activity
      was not affected by matrix metalloproteinase inhibitors but could be almost
      completely abrogated by inhibiting cathepsins L and S. These data demonstrate
      that human macrophages mobilize cysteine proteinases to arm themselves with a
      powerful effector mechanism that can participate in the pathophysiologic
      remodeling of the extracellular matrix.

PMID- 7731996
TI  - Degradation of the cleaved leader peptide of thiolase by a peroxisomal
      proteinase.
AB  - A peroxisomal location for insulin-degrading enzyme (IDE) has been defined by
      confocal immunofluorescence microscopy of stably transfected CHO cells
      overexpressing IDE and digitonin-permeabilization studies in normal
      nontransfected fibroblasts. The functional significance of IDE in degrading
      cleaved leader peptides of peroxisomal proteins targeted by the type II motif was
      evaluated with a synthetic peptide corresponding to the type II leader peptide of
      prethiolase. The peptide effectively competed for degradation and cross-linking
      of the high-affinity substrate 125I-labeled insulin to IDE. Direct proteolysis of
      the leader peptide of prethiolase was confirmed by HPLC; degradation was
      inhibited by immunodepletion with an antibody to IDE. Phylogenetic analysis of
      proteinases related to IDE revealed sequence similarity to mitochondrial
      processing peptidases.

PMID- 7731997
TI  - Structural interpretation of the mutations in the beta-cardiac myosin that have
      been implicated in familial hypertrophic cardiomyopathy.
AB  - In 10-30% of hypertrophic cardiomyopathy kindreds, the disease is caused by > 29
      missense mutations in the cardiac beta-myosin heavy chain (MYH7) gene. The amino
      acid sequence similarity between chicken skeletal muscle and human beta-cardiac
      myosin and the three-dimensional structure of the chicken skeletal muscle myosin
      head have provided the opportunity to examine the structural consequences of
      these naturally occurring mutations in human beta-cardiac myosin. This study
      demonstrates that the mutations are related to distinct structural and functional
      domains. Twenty-four are clustered around four specific locations in the myosin
      head that are (i) associated with the actin binding interface, (ii) around the
      nucleotide binding site, (iii) adjacent to the region that connects the two
      reactive cysteine residues, and (iv) in close proximity to the interface of the
      heavy chain with the essential light chain. The remaining five mutations are in
      the myosin rod. The locations of these mutations provide insight into the way
      they impair the functioning of this molecular motor and also into the mechanism
      of energy transduction.

PMID- 7731998
TI  - Bacteriophage T7 helicase/primase proteins form rings around single-stranded DNA
      that suggest a general structure for hexameric helicases.
AB  - Most helicases studied to date have been characterized as oligomeric, but the
      relation between their structure and function has not been understood. The
      bacteriophage T7 gene 4 helicase/primase proteins act in T7 DNA replication. We
      have used electron microscopy, three-dimensional reconstruction, and protein
      crosslinking to demonstrate that both proteins form hexameric rings around single
      stranded DNA. Each subunit has two lobes, so the hexamer appears to be two
      tiered, with a small ring stacked on a large ring. The single-stranded DNA passes
      through the central hole of the hexamer, and the data exclude substantial
      wrapping of the DNA about or within the protein ring. Further, the hexamer binds
      DNA with a defined polarity as the smaller ring of the hexamer points toward the
      5' end of the DNA. The similarity in three-dimensional structure of the T7 gene 4
      proteins to that of the Escherichia coli RuvB helicase suggests that polar rings
      assembled around DNA may be a general feature of numerous hexameric helicases
      involved in DNA replication, transcription, recombination, and repair.

PMID- 7731999
TI  - Stable loop in the crystal structure of the intercalated four-stranded cytosine
      rich metazoan telomere.
AB  - In most metazoans, the telomeric cytosine-rich strand repeating sequence is
      d(TAACCC). The crystal structure of this sequence was solved to 1.9-A resolution.
      Four strands associate via the cytosine-containing parts to form a four-stranded
      intercalated structure held together by C.C+ hydrogen bonds. The base-paired
      strands are parallel to each other, and the two duplexes are intercalated into
      each other in opposite orientations. One TAA end forms a highly stabilized loop
      with the 5' thymine Hoogsteen-base-paired to the third adenine. The 5' end of
      this loop is in close proximity to the 3' end of one of the other intercalated
      cytosine strands. Instead of being entirely in a DNA duplex, this structure
      suggests the possibility of an alternative conformation for the cytosine-rich
      telomere strands.

PMID- 7732000
TI  - In vitro cleavage and joining at the viral origin of replication by the
      replication initiator protein of tomato yellow leaf curl virus.
AB  - Replication of the single-stranded DNA genome of geminiviruses occurs via a
      double-stranded intermediate that is subsequently used as a template for rolling
      circle replication of the viral strand. Only one of the proteins encoded by the
      virus, here referred to as replication initiator protein (Rep protein), is
      indispensable for replication. We show that the Rep protein of tomato yellow leaf
      curl virus initiates viral-strand DNA synthesis by introducing a nick in the plus
      strand within the nonanucleotide 1TAATATT decreases 8AC, identical among all
      geminiviruses. After cleavage, the Rep protein remains bound to the 5' end of the
      cleaved strand. In addition, we show that the Rep protein has a joining activity,
      suggesting that it acts as a terminase, thus resolving the nascent viral single
      strand into genome-sized units.

PMID- 7732001
TI  - Repressible cation-phosphate symporters in Neurospora crassa.
AB  - The filamentous fungus Neurospora crassa possesses two nonhomologous high
      affinity phosphate permeases, PHO-4 and PHO-5. We have isolated separate null
      mutants of these permeases, allowing us to study the remaining active transporter
      in vivo in terms of phosphate uptake and sensitivity to inhibitors. The
      specificity for the cotransported cation differs for PHO-4 and PHO-5, suggesting
      that these permeases employ different mechanisms for phosphate translocation.
      Phosphate uptake by PHO-4 is stimulated 85-fold by the addition of Na+, which
      supports the idea that PHO-4 is a Na(+)-phosphate symporter. PHO-5 is unaffected
      by Na+ concentration but is much more sensitive to elevated pH than is PHO-4.
      Presumably, PHO-5 is a H(+)-phosphate symporter. Na(+)-coupled symport is usually
      associated with animal cells. The finding of such a system in a filamentous
      fungus is in harmony with the idea that the fungal and animal kingdoms are more
      closely related to each other than either is to the plant kingdom.

PMID- 7732002
TI  - Scrambling of the actin I gene in two Oxytricha species.
AB  - The DNA in a germ-line nucleus (a micronucleus) undergoes extensive processing
      when it develops into a somatic nucleus (a macronucleus) after cell mating in
      hypotrichous ciliates. Processing includes destruction of a large amount of
      spacer DNA between genes and excision of gene-sized molecules from chromosomes.
      Before processing, micronuclear genes are interrupted by numerous noncoding
      segments called internal eliminated sequences (IESs). The IESs are excised and
      destroyed, and the retained macro-nuclear-destined sequences (MDSs) are spliced.
      MDSs in some micronuclear genes are not in proper order and must be reordered
      during processing to create functional gene-sized molecules for the macronucleus.
      Here we report that the micronuclear actin I gene in Oxytricha trifallax WR
      consists of 10 MDSs and 9 IESs compared to the previously reported 9 MDSs and 8
      IESs in the micronuclear actin I gene of Oxytricha nova. The MDSs in the actin I
      gene are scrambled in a similar pattern in the two species, but the positions of
      MDS-IES junctions are shifted by up to 14 bp for scrambled and 138 bp for the
      nonscrambled MDSs. The shifts in MDS-IES junctions create differences in the
      repeat sequences that are believed to guide MDS splicing. Also, the sizes and
      sequences of IESs in the micronuclear actin I genes are different in the two
      Oxytricha species. These observations give insight about the possible origins of
      IES insertion and MDS scrambling in evolution and show the extraordinary
      malleability of the germ-line DNA in hypotrichs.

PMID- 7732003
TI  - T lymphocytes from human atherosclerotic plaques recognize oxidized low density
      lipoprotein.
AB  - Atherosclerosis, an underlying cause of myocardial infarction, stroke, and other
      cardiovascular diseases, consists of focal plaques characterized by cholesterol
      deposition, fibrosis, and inflammation. The presence of activated T lymphocytes
      and macrophages and high expression of HLA class II molecules are indicative of a
      local immunologic activation in the atherosclerotic plaque, but the antigen(s)
      involved has not yet been identified. We established T-cell clones from human
      atherosclerotic plaques using polyclonal mitogens as stimuli and exposed the
      clones to potential antigens in the presence of autologous monocytes as antigen
      presenting cells. Four of the 27 CD4+ clones responded to oxidized low density
      lipoprotein (oxLDL) by proliferation and cytokine secretion; this response was
      dependent on autologous antigen-presenting cells and restricted by HLA-DR. All
      clones that responded to oxLDL secreted interferon gamma upon activation, but
      only one produced interleukin 4, suggesting that the response to oxLDL results in
      immune activation and inflammation but may not be a strong stimulus to antibody
      production. No significant response to oxLDL could be detected in CD4+ T-cell
      clones derived from the peripheral blood of the same individuals. Together, the
      present data suggest that the inflammatory infiltrate in the atherosclerotic
      plaque is involved in a T-cell-dependent, autoimmune response to oxLDL.

PMID- 7732004
TI  - A gene encoding a phosphatidylinositol-specific phospholipase C is induced by
      dehydration and salt stress in Arabidopsis thaliana.
AB  - A cDNA corresponding to a putative phosphatidylinositol-specific phospholipase C
      (PI-PLC) in the higher plant Arabidopsis thaliana was cloned by use of the
      polymerase chain reaction. The cDNA, designated cAtPLC1, encodes a putative
      polypeptide of 561 aa with a calculated molecular mass of 64 kDa. The putative
      product includes so-called X and Y domains found in all PI-PLCs identified to
      date. In mammalian cells, there are three types of PI-PLC, PLC-beta, -gamma, and 
      delta. The overall structure of the putative AtPLC1 protein is most similar to
      that of PLC-delta, although the AtPLC1 protein is much smaller than PLCs from
      other organisms. The recombinant AtPLC1 protein synthesized in Escherichia coli
      was able to hydrolyze phosphatidylinositol 4,5-bisphosphate and this activity was
      completely dependent on Ca2+, as observed also for mammalian PI-PLCs. These
      results suggest that the AtPLC1 gene encodes a genuine PI-PLC of a higher plant.
      Northern blot analysis showed that the AtPLC1 gene is expressed at very low
      levels in the plant under normal conditions but is induced to a significant
      extent under various environmental stresses, such as dehydration, salinity, and
      low temperature. These observations suggest that AtPLC1 might be involved in the
      signal-transduction pathways of environmental stresses and that an increase in
      the level of AtPLC1 might amplify the signal, in a manner that contributes to the
      adaptation of the plant to these stresses.

PMID- 7732005
TI  - Prenatal monocular enucleation induces a selective loss of low-spatial-frequency
      cortical responses to the remaining eye.
AB  - During early development, interactions between the two eyes are critical in the
      formation of eye-specific domains within the lateral geniculate nucleus and the
      visual cortex. When monocular enucleation is done early in prenatal life, it
      induces remarkable anatomical and functional reorganizations of the visual
      pathways. Behavioral data have shown a loss in sensitivity to low-spatial
      frequency gratings in cats. To correlate the behavioral observations with a
      possible change in the analysis of contrast at the level of primary visual areas
      we recorded visual evoked potentials at the 17/18 border in two cats enucleated
      prenatally (gestational age at enucleation, 39-42 days), three neonatal, two
      control animals, and one animal with a surgical removal of Y-ganglion fibers. Our
      results show a strong attenuation in the amplitude of response at all contrast
      values for gratings of low spatial frequency in prenatally enucleated cats,
      whereas neonatally enucleated and control animals present responses of comparable
      amplitude. We conclude that the behavioral results reflect the reduced
      sensitivity for low frequencies of visual cortical neurons. In addition, we
      define a critical period for the development of the contrast-sensitivity function
      that seems to be limited to the prenatal gestation period. We suggest that the
      prenatal interruption of binocular interactions leads to a functional elimination
      of the Y-ganglion system.

PMID- 7732006
TI  - Species specificity in the cell-free conversion of prion protein to protease
      resistant forms: a model for the scrapie species barrier.
AB  - Scrapie is a transmissible neurodegenerative disease that appears to result from
      an accumulation in the brain of an abnormal protease-resistant isoform of prion
      protein (PrP) called PrPsc. Conversion of the normal, protease-sensitive form of
      PrP (PrPc) to protease-resistant forms like PrPsc has been demonstrated in a cell
      free reaction composed largely of hamster PrPc and PrPsc. We now report studies
      of the species specificity of this cell-free reaction using mouse, hamster, and
      chimeric PrP molecules. Combinations of hamster PrPc with hamster PrPsc and mouse
      PrPc with mouse PrPsc resulted in the conversion of PrPc to protease-resistant
      forms. Protease-resistant PrP species were also generated in the nonhomologous
      reaction of hamster PrPc with mouse PrPsc, but little conversion was observed in
      the reciprocal reaction. Glycosylation of the PrPc precursors was not required
      for species specificity in the conversion reaction. The relative conversion
      efficiencies correlated with the relative transmissibilities of these strains of
      scrapie between mice and hamsters. Conversion experiments performed with chimeric
      mouse/hamster PrPc precursors indicated that differences between PrPc and PrPsc
      at residues 139, 155, and 170 affected the conversion efficiency and the size of
      the resultant protease-resistant PrP species. We conclude that there is species
      specificity in the cell-free interactions that lead to the conversion of PrPc to
      protease-resistant forms. This specificity may be the molecular basis for the
      barriers to interspecies transmission of scrapie and other transmissible
      spongiform encephalopathies in vivo.

PMID- 7732008
TI  - The murine stk gene product, a transmembrane protein tyrosine kinase, is a
      receptor for macrophage-stimulating protein.
AB  - Macrophage-stimulating protein (MSP) was originally identified as an inducer of
      murine resident peritoneal macrophage responsiveness to chemoattractants. We
      recently showed that the product of RON, a protein tyrosine kinase cloned from a
      human keratinocyte library, is the receptor for MSP. Similarity of murine stk to
      RON led us to determine if the stk gene product is the murine receptor for MSP.
      Radiolabeled MSP could bind to NIH 3T3 cells transfected with murine stk cDNA
      (3T3/stk). Binding was saturable and was inhibited by unlabeled MSP but not by
      structurally related proteins, including hepatocyte growth factor and
      plasminogen. Specific binding to STK was demonstrated by cross-linking of 125I
      labeled MSP to membrane proteins of 3T3/stk cells, which resulted in a protein
      complex with a molecular mass of 220 kDa. This radiolabeled complex comprised
      125I-MSP and STK, since it could be immunoprecipitated by antibodies to the STK
      beta chain. Binding of MSP to stk cDNA-transfected cells induced tyrosine
      phosphorylation of the 150-kDa STK beta chain within 1 min and caused increased
      motile activity. These results establish the murine stk gene product as a
      specific transmembrane protein tyrosine kinase receptor for MSP. Inasmuch as the
      stk cDNA was cloned from a hematopoietic stem cell, our data suggest that in
      addition to macrophages and keratinocytes, a cell in the hematopoietic lineage
      may also be a target for MSP.

PMID- 7732007
TI  - Disease specificity of kinase domains: the src-encoded catalytic domain converts
      erbB into a sarcoma oncogene.
AB  - src and erbB are two tyrosine kinase-encoding oncogenes carried by retroviruses,
      which have distinct disease specificities. The former induces predominantly
      sarcomas, and the latter, leukemias. Src and ErbB have similar catalytic domains
      but have very different regulatory domains. A wealth of information exists
      concerning how different regulatory domains [Src homology 2 (SH2) and SH3 domains
      and autophosphorylation sites] control substrate and disease specificities.
      Whether the catalytic domain helps determine these specificities remains to be
      explored. Here we show that the Src catalytic domain is enzymatically active when
      substituted into the ErbB backbone and interacts with the ErbB regulatory domain.
      This ErbB/Src chimera displays autophosphorylation and substrate phosphorylation
      patterns different from those of both Src and ErbB. Neither SH2 and SH3 nor
      autophosphorylation sites are required for the Src catalytic domain to exert its
      fibroblast transforming ability. Most significantly, the catalytic domain can
      convert erbB from a leukemogenic oncogene into a sarcomagenic oncogene,
      suggesting that the leukemogenic determinants in part reside within the ErbB
      catalytic domain.

PMID- 7732009
TI  - Receptor usage and differential downregulation of CD46 by measles virus wild-type
      and vaccine strains.
AB  - Recently, two cell surface molecules, CD46 and moesin, have been found to be
      functionally associated with measles virus (MV) infectivity of cells. We
      investigated the receptor usage of MV wild-type, subacute sclerosing
      panencephalitis, and vaccine strains and their effect on the down-regulation of
      CD46 after infection. We found that the infection of human cell lines with all 19
      MV strains tested was inhibitable with antibodies against CD46. In contrast, not
      all strains of MV led to the downregulation of CD46 following infection. The
      group of CD46 non-downregulating strains comprised four lymphotropic wild-type
      isolates designated AB, DF, DL, and WTF. Since the downregulation of CD46 is
      caused by interaction with newly synthesized MV hemagglutinin (MV-H), we tested
      the capability of recombinant MV-H proteins to downregulate CD46. Recombinant MV
      H proteins of MV strains Edmonston, Halle, and CM led to the down-regulation of
      CD46, whereas those of DL and WTF did not. This observed differential
      downregulation by different MV strains has profound consequences, since lack of
      CD46 on the cell surface leads to susceptibility of cells to complement lysis.
      These results suggest that lymphotropic wild-type strains of MV which do not
      downregulate CD46 may have an advantage for replication in vivo. The relatively
      weak immune response against attenuated vaccine strains of MV compared with wild
      type strains might be related to this phenomenon.

PMID- 7732010
TI  - D-serine, an endogenous synaptic modulator: localization to astrocytes and
      glutamate-stimulated release.
AB  - Using an antibody highly specific for D-serine conjugated to glutaraldehyde, we
      have localized endogenous D-serine in rat brain. Highest levels of D-serine
      immunoreactivity occur in the gray matter of the cerebral cortex, hippocampus,
      anterior olfactory nucleus, olfactory tubercle, and amygdala. Localizations of D
      serine immunoreactivity correlate closely with those of D-serine binding to the
      glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor as visualized
      by autoradiography and are inversely correlated to the presence of D-amino acid
      oxidase. D-Serine is enriched in process-bearing glial cells in neuropil with the
      morphology of protoplasmic astrocytes. In glial cultures of rat cerebral cortex,
      D-serine is enriched in type 2 astrocytes. The release of D-serine from these
      cultures is stimulated by agonists of non-NMDA glutamate receptors, suggesting a
      mechanism by which astrocyte-derived D-serine could modulate neurotransmission. D
      Serine appears to be the endogenous ligand for the glycine site of NMDA
      receptors.

PMID- 7732011
TI  - Functional interactions between the retinoblastoma (Rb) protein and Sp-family
      members: superactivation by Rb requires amino acids necessary for growth
      suppression.
AB  - The transient expression of the retinoblastoma protein (Rb) regulates the
      transcription of a variety of growth-control genes, including c-fos, c-myc, and
      the gene for transforming growth factor beta 1 via discrete promoter sequences
      termed retinoblastoma control elements (RCE). Previous analyses have shown that
      Sp1 is one of three RCE-binding proteins identified in nuclear extracts and that
      Rb functionally interacts with Sp1 in vivo, resulting in the "superactivation" of
      Sp1-mediated transcription. By immunochemical and biochemical criteria, we report
      that an Sp1-related transcription factor, Sp3, is a second RCE-binding protein.
      Furthermore, in transient cotransfection assays, we report that Rb
      "superactivates" Sp3-mediated RCE-dependent transcription in vivo and that levels
      of superactivation are dependent on the trans-activator (Sp1 or Sp3) studied.
      Using expression vectors carrying mutated Rb cDNAs, we have identified two
      portions of Rb required for superactivation: (i) a portion of the Rb "pocket"
      (amino acids 614-839) previously determined to be required for physical
      interactions between Rb and transcription factors such as E2F-1 and (ii) a novel
      amino-terminal region (amino acids 140-202). Since both of these regions of Rb
      are targets of mutation in human tumors, our data suggest that superactivation of
      Sp1/Sp3 may play a role in Rb-mediated growth suppression and/or the induction of
      differentiation.

PMID- 7732012
TI  - Increased sensitivity to gamma irradiation in bacteria lacking protein HU.
AB  - The heterodimeric HU protein, isolated from Escherichia coli, is associated with
      the bacterial nucleoid and shares some properties with both histones and HMG
      proteins. It is the prototype of small bacterial DNA binding proteins with a
      pleiotropic role in the cell. HU participates in several biological processes
      like cell division, initiation of DNA replication, transposition, and other
      biochemical functions. We show here that bacteria lacking HU are extremely
      sensitive to gamma irradiation. Expression of either one of the subunits of HU in
      the hupAB double mutant nearly restores the normal survival rate. This shows that
      the sensitivity is due to the absence of HU rather than being the result of a
      secondary mutation occurring in the hupAB cells or a modification of the SOS
      repair system, since SOS genes are induced normally in the absence of HU.
      Finally, in vitro studies give an indication of its potential role: HU protects
      DNA against cleavage by gamma-rays.

PMID- 7732013
TI  - A simple p53 functional assay for screening cell lines, blood, and tumors.
AB  - Mutations in the p53 gene are implicated in the pathogenesis of half of all human
      tumors. We have developed a simple functional assay for p53 mutation in which
      human p53 expressed in Saccharomyces cerevisiae activates transcription of the
      ADE2 gene. Consequently, yeast colonies containing wild-type p53 are white and
      colonies containing mutant p53 are red. Since this assay tests the critical
      biological function of p53, it can distinguish inactivating mutations from
      functionally silent mutations. By combining this approach with gap repair
      techniques in which unpurified p53 reverse transcription-PCR products are cloned
      by homologous recombination in vivo it is possible to screen large numbers of
      samples and multiple clones per sample for biologically important mutations. This
      means that mutations can be detected in tumor specimens contaminated with large
      amounts of normal tissue. In addition, the assay detects temperature-sensitive
      mutants, which give pink colonies. We show here that this form of p53 functional
      assay can be used rapidly to detect germline mutations in blood samples, somatic
      mutations in tumors, and mutations in cell lines.

PMID- 7732014
TI  - A Xenopus distal-less gene in transgenic mice: conserved regulation in distal
      limb epidermis and other sites of epithelial-mesenchymal interaction.
AB  - In this paper, we show the conserved regulation of the homeodomain gene Distal
      less-3 (Dlx-3) by analyzing the expression of a promoter from the Xenopus
      ortholog, Xdll-2, in transgenic mice. A 470-bp frog regulatory sequence confers
      appropriate expression on a lacZ reporter gene in the ectodermal component of
      structures derived from epithelial-mesenchymal interactions. Remarkably, this
      includes structures absent in Xenopus, such as the hair follicle and mammary
      gland, suggesting that conserved regulatory elements can be used to control the
      formation of structures peculiar to individual species. In addition, expression
      of Dlx-3 in developing limbs is highest at the most distal portion. This pattern
      is duplicated by the Xenopus promoter, indicating that this DNA may include
      sequences responsive to conserved proximodistal patterning signals in the
      vertebrate limb.

PMID- 7732015
TI  - Polyadenylylation destabilizes the rpsO mRNA of Escherichia coli.
AB  - The rpsO mRNA, encoding ribosomal protein S15, is only partly stabilized when the
      three ribonucleases implicated in its degradation--RNase E, polynucleotide
      phosphorylase, and RNase II--are inactivated. In the strain deficient for RNase E
      and 3'-to-5' exoribonucleases, degradation of this mRNA is correlated with the
      appearance of posttranscriptionally elongated molecules. We report that these
      elongated mRNAs harbor poly(A) tails, most of which are fused downstream of the
      3'-terminal hairpin at the site where transcription terminates. Poly(A) tails are
      shorter in strains containing 3'-to-5' exoribonucleases. Inactivation of poly(A)
      polymerase I (pcnB) prevents polyadenylylation and stabilizes the rpsO mRNA if
      RNase E is inactive. In contrast polyadenylylation does not significantly modify
      the stability of rpsO mRNA undergoing RNase E-mediated degradation.

PMID- 7732016
TI  - Transendothelial migration of neutrophils involves integrin-associated protein
      (CD47).
AB  - Inflammation is a primary pathological process. The development of an
      inflammatory reaction involves the movement of white blood cells through the
      endothelial lining of blood vessels into tissues. This process of
      transendothelial cell migration of neutrophils has been shown to involve
      neutrophil beta 2 integrins (CD18) and endothelial cell platelet-endothelium cell
      adhesion molecules (PECAM-1; CD31). We now show that F(ab')2 fragments of the
      monoclonal antibody B6H12 against integrin-associated protein (IAP) blocks the
      transendothelial migration of neutrophils stimulated by an exogenous gradient of
      the chemokine interleukin 8 (IL-8; 60% inhibition), by the chemotactic peptide N
      formyl-methionylleucylphenylalanine (FMLP; 76% inhibition), or by the activation
      of the endothelium by the cytokine tumor necrosis factor alpha (98% inhibition).
      The antibody has two mechanisms of action: on neutrophils it prevents the
      chemotactic response to IL-8 and FMLP, and on endothelium it prevents an unknown
      but IL-8-independent process. Blocking antibodies to IAP do not alter the
      expression of adhesion proteins or production of IL-8 by endothelial cells, and
      thus the inhibition of neutrophil transendothelial migration is selective. These
      data implicate IAP as the third molecule essential for neutrophil migration
      through endothelium into sites of inflammation.

PMID- 7732017
TI  - Founder-effect speciation theory: failure of experimental corroboration.
AB  - The theory of founder-effect speciation proposes that colonization by very few
      individuals of an empty habitat favors rapid genetic changes and the evolution of
      a new species. We report here the results obtained in a 10-year-long and large
      scale experiment with Drosophila pseudoobscura designed to test the theory. In
      our experimental protocol, populations are established with variable numbers of
      very few individuals and allowed to expand greatly for several generations until
      conditions of severe competition for resources are reached and the population
      crashes. A few random survivors are then taken to start a new population
      expansion and thus initiate a new cycle of founding events, population flushes,
      and crashes. Our results provide no support for the theories proposing that new
      species are very likely to appear as by-products of founder events.

PMID- 7732018
TI  - Recombinant Listeria monocytogenes as a live vaccine vehicle for the induction of
      protective anti-viral cell-mediated immunity.
AB  - Listeria monocytogenes (LM) is a Gram-positive bacterium that is able to enter
      host cells, escape from the endocytic vesicle, multiply within the cytoplasm, and
      spread directly from cell to cell without encountering the extracellular milieu.
      The ability of LM to gain access to the host cell cytosol allows proteins
      secreted by the bacterium to efficiently enter the pathway for major
      histocompatibility complex class I antigen processing and presentation. We have
      established a genetic system for expression and secretion of foreign antigens by
      recombinant strains, based on stable site-specific integration of expression
      cassettes into the LM genome. The ability of LM recombinants to induce protective
      immunity against a heterologous pathogen was demonstrated with lymphocytic
      choriomeningitis virus (LCMV). LM strains expressing the entire LCMV
      nucleoprotein or an H-2Ld-restricted nucleoprotein epitope (aa 118-126) were
      constructed. Immunization of mice with LM vaccine strains conferred protection
      against challenge with virulent strains of LCMV that otherwise establish chronic
      infection in naive adult mice. In vivo depletion of CD8+ T cells from vaccinated
      mice abrogated their ability to clear viral infection, showing that protective
      anti-viral immunity was due to CD8+ T cells.

PMID- 7732019
TI  - Life-span, T-cell responses, and incidence of lymphomas in congenic mice.
AB  - Survival, T-cell functions, and postmortem histopathology were studied in H-2
      congenic strains of mice bearing H-2b, H-2k, and H-2d haplotypes. Males lived
      longer than females in all homozygous and heterozygous combinations except for H
      2d homozygotes, which showed no differences between males and females.
      Association of heterozygosity with longer survival was observed only with H-2b/H
      2b and H-2b/H-2d mice. Analysis using classification and regression trees (CART)
      showed that both males and females of H-2b homozygous and H-2k/H-2b mice had the
      shortest life-span of the strains studied. In histopathological analyses,
      lymphomas were noted to be more frequent in females, while hemangiosarcomas and
      hepatomas were more frequent in males. Lymphomas appeared earlier than hepatomas
      or hemangiosarcomas. The incidence of lymphomas was associated with the H-2
      haplotype--e.g., H-2b homozygous mice had more lymphomas than did mice of the H
      2d haplotype. More vigorous T-cell function was maintained with age (27 months)
      in H-2d, H-2b/H-2d, and H-2d/H-2k mice as compared with H-2b, H-2k, and H-2b/H-2k
      mice, which showed a decline of T-cell responses with age.

PMID- 7732020
TI  - Free, long-chain, polyunsaturated fatty acids reduce membrane electrical
      excitability in neonatal rat cardiac myocytes.
AB  - Because previous studies showed that polyunsaturated fatty acids can reduce the
      contraction rate of spontaneously beating heart cells and have antiarrhythmic
      effects, we examined the effects of the fatty acids on the electrophysiology of
      the cardiac cycle in isolated neonatal rat cardiac myocytes. Exposure of
      cardiomyocytes to 10 microM eicosapentaenoic acid for 2-5 min markedly increased
      the strength of the depolarizing current required to elicit an action potential
      (from 18.0 +/- 2.4 pA to 26.8 +/- 2.7 pA, P < 0.01) and the cycle length of
      excitability (from 525 ms to 1225 ms, delta = 700 +/- 212, P < 0.05). These
      changes were due to an increase in the threshold for action potential (from -52
      mV to -43 mV, delta = 9 +/- 3, P < 0.05) and a more negative resting membrane
      potential (from -52 mV to -57 mV, delta = 5 +/- 1, P < 0.05). There was a
      progressive prolongation of intervals between spontaneous action potentials and a
      slowed rate of phase 4 depolarization. Other polyunsaturated fatty acids-
      including docosahexaenoic acid, linolenic acid, linoleic acid, arachidonic acid,
      and its nonmetabolizable analog eicosatetraynoic acid, but neither the
      monounsaturated oleic acid nor the saturated stearic acid--had similar effects.
      The effects of the fatty acids could be reversed by washing with fatty acid-free
      bovine serum albumin. These results show that free polyunsaturated fatty acids
      can reduce membrane electrical excitability of heart cells and provide an
      electrophysiological basis for the antiarrhythmic effects of these fatty acids.

PMID- 7732021
TI  - Spatial organization of retinal information about the direction of image motion.
AB  - The visual stimuli that elicit neural activity differ for different retinal
      ganglion cells and these cells have been categorized by the visual information
      that they transmit. If specific visual information is conveyed exclusively or
      primarily by a particular set of ganglion cells, one might expect the cells to be
      organized spatially so that their sampling of information from the visual field
      is complete but not redundant. In other words, the laterally spreading dendrites
      of the ganglion cells should completely cover the retinal plane without gaps or
      significant overlap. The first evidence for this sort of arrangement, which has
      been called a tiling or tessellation, was for the two types of "alpha" ganglion
      cells in cat retina. Other reports of tiling by ganglion cells have been made
      subsequently. We have found evidence of a particularly rigorous tiling for the
      four types of ganglion cells in rabbit retina that convey information about the
      direction of retinal image motion (the ON-OFF direction-selective cells).
      Although individual cells in the four groups are morphologically
      indistinguishable, they are organized as four overlaid tilings, each tiling
      consisting of like-type cells that respond preferentially to a particular
      direction of retinal image motion. These observations lend support to the
      hypothesis that tiling is a general feature of the organization of information
      outflow from the retina and clearly implicate mechanisms for recognition of like
      type cells and establishment of mutually acceptable territories during retinal
      development.

PMID- 7732022
TI  - Cyclin-dependent protein kinase and cyclin homologs SSN3 and SSN8 contribute to
      transcriptional control in yeast.
AB  - The SSN3 and SSN8 genes of Saccharomyces cerevisiae were identified by mutations
      that suppress a defect in SNF1, a protein kinase required for release from
      glucose repression. Mutations in SSN3 and SSN8 also act synergistically with a
      mutation of the MIG1 repressor protein to relieve glucose repression. We have
      cloned the SSN3 and SSN8 genes. SSN3 encodes a cyclin-dependent protein kinase
      (cdk) homolog and is identical to UME5. SSN8 encodes a cyclin homolog 35%
      identical to human cyclin C. SSN3 and SSN8 fusion proteins interact in the two
      hybrid system and coimmunoprecipitate from yeast cell extracts. Using an immune
      complex assay, we detected protein kinase activity that depends on both SSN3 and
      SSN8. Thus, the two SSN proteins are likely to function as a cdk-cyclin pair.
      Genetic analysis indicates that the SSN3-SSN8 complex contributes to
      transcriptional repression of diversely regulated genes and also affects
      induction of the GAL1 promoter.

PMID- 7732023
TI  - Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence
      for two isoforms.
AB  - We have cloned and sequenced the cDNA coding for human HepG2 acetyl-CoA
      carboxylase (ACC; EC 6.4.1.2). The sequence has an open reading frame of 7038 bp
      that encode 2346 amino acids (M(r), 264,737). The C-terminal 2.6-kb sequence is
      very different from that recently reported for human ACC (Ha, J., Daniel, S.,
      Kong, I.-S., Park, C.-K., Tae, H.-J. & Kim, K.-H. [1994] Eur. J. Biochem. 219,
      297-306). Northern blot analysis revealed that the ACC mRNA is approximately 10
      kb in size and that its level varies among the tissues tested. Evidence is
      presented to show that the human ACC gene is 200-480 kbp in size and maps to
      chromosome 17q12. We also provide evidence for the presence of another ACC-like
      gene with similarly sized mRNA but tissue-specific expression different from that
      of the ACC gene reported herein. That this second ACC-like gene encodes the 280
      kDa carboxylase is not ruled out.

PMID- 7732024
TI  - Rod photoreceptor-specific gene expression in human retinoblastoma cells.
AB  - Retinoblastoma cells in culture have previously been shown to express cone
      specific genes but not their rod counterparts. We have detected the messages for
      the rod alpha, beta, and gamma subunits of cGMP phosphodiesterase (PDE), the rod
      alpha subunit of transducin, rod opsin, and the cone alpha' subunit of PDE in RNA
      of human Y-79 retinoblastoma cells by reverse transcription-PCR. Quantitative
      analysis of the mRNAs for the rod alpha and cone alpha' PDE subunits revealed
      that they were expressed at comparable levels; however, the transcript encoding
      the rod beta PDE subunit was 10 times more abundant in these cells. Northern
      hybridization analysis of Y-79 cell RNA confirmed the presence of the transcripts
      for rod and cone PDE catalytic subunits. To test whether the transcriptional
      machinery required for the expression of rod-specific genes was endogenous in Y
      79 retinoblastoma cells, cultures were transfected with a construct containing
      the promoter region of the rod beta PDE subunit gene attached to the firefly
      luciferase reporter vector. Significant levels of reporter enzyme activity were
      observed in the cell lysates. Our results demonstrate that the Y-79
      retinoblastoma cell line is a good model system for the study of transcriptional
      regulation of rod-specific genes.

PMID- 7732025
TI  - Peptide mimicry of the meningococcal group C capsular polysaccharide.
AB  - Sequence analysis of the variable regions of the heavy and light chains of the
      anti-idiotypic antibody 6F9, which mimics the meningococcal group C capsular
      polysaccharide (MCP), was performed. The immunogenic site on 6F9 responsible for
      inducing an anti-MCP antibody response was determined by means of sequence and
      computer model analysis of these data. Complementarity-determining region 3
      (CDR3) was found to be unique in that the sequence tract YRY was exposed on the
      surface. A synthetic peptide spanning the CDR3 domain was synthesized and
      complexed to proteosomes (meningococcal group B outer membrane protein).
      Immunizations of BALB/c mice with the peptide-proteosome complex resulted in a
      significant anti-MCP antibody response. Immunized mice were protected against
      infection with a lethal dose of Neisseria meningitidis serogroup C.

PMID- 7732026
TI  - Differential activation of proliferation and cytotoxicity in human T-cell
      lymphotropic virus type I Tax-specific CD8 T cells by an altered peptide ligand.
AB  - Human T-cell leukemia virus type I (HTLV-I) gives rise to a neurologic disease
      known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
      Although the pathogenesis of the disease is unknown, the presence of a remarkably
      high frequency of Tax-specific, cytotoxic CD8 T cells may suggest a role of these
      cells in the development of HAM/TSP. Antigen-mediated signaling in a CD8 T-cell
      clone specific for the Tax(11-19) peptide of HTLV-I was studied using analog
      peptides substituted in their T-cell receptor contact residues defined by x-ray
      crystallographic data of the Tax(11-19) peptide in the groove of HLA-A2. CD8 T
      cell stimulation with the wild-type peptide antigen led to activation of p56lck
      kinase activity, interleukin 2 secretion, cytotoxicity, and clonal expansion. A
      Tax analog peptide with an alanine substitution of the T-cell receptor contact
      residue tyrosine-15 induced T-cell-mediated cytolysis without activation of
      interleukin 2 secretion or proliferation. Induction of p56lck kinase activity
      correlated with T-cell-mediated cytotoxicity, whereas interleukin 2 secretion
      correlated with [3H]thymidine incorporation and proliferation. Moreover, Tax
      peptide analogs that activated the tyrosine kinase activity of p56lck could
      induce unresponsiveness to secondary stimulation with the wild-type peptide.
      These observations show that a single amino acid substitution in a T-cell
      receptor contact residue of Tax can differentially signal CD8 T cells and further
      demonstrate that primary activation has functional consequences for the secondary
      response of at least some Tax-specific CD8 T cells to HTLV-I-infected target
      cells.

PMID- 7732027
TI  - Isolation and molecular characterization of a human T-cell lymphotropic virus
      type II (HTLV-II), subtype B, from a healthy Pygmy living in a remote area of
      Cameroon: an ancient origin for HTLV-II in Africa.
AB  - We report characterization of a human T-cell lymphotropic virus type II (HTLV-II)
      isolated from an interleukin 2-dependent CD8 T-cell line derived from peripheral
      blood mononuclear cells of a healthy, HTLV-II-seropositive female Bakola Pygmy,
      aged 59, living in a remote equatorial forest area in south Cameroon. This HTLLV
      II isolate, designated PYGCAM-1, reacted in an indirect immunofluorescence assay
      with HTLV-II and HTLV-I polyclonal antibodies and with an HTLV-I/II gp46
      monoclonal antibody but not with HTLV-I gag p19 or p24 monoclonal antibodies. The
      cell line produced HTLV-I/II p24 core antigen and retroviral particles. The
      entire env gene (1462 bp) and most of the long terminal repeat (715 bp) of the
      PYGCAM-1 provirus were amplified by the polymerase chain reaction using HTLV-II
      specific primers. Comparison with the long terminal repeat and envelope sequences
      of prototype HTLV-II strains indicated that PYGCAM-1 belongs to the subtype B
      group, as it has only 0.5-2% nucleotide divergence from HTLV-II B strains. The
      finding of antibodies to HTLV-II in sera taken from the father of the woman in
      1984 and from three unrelated members of the same population strongly suggests
      that PYGCAM-1 is a genuine HTLV-II that has been present in this isolated
      population for a long time. The low genetic divergence of this African isolate
      from American isolates raises questions about the genetic variability over time
      and the origin and dissemination of HTLV-II, hitherto considered to be
      predominantly a New World virus.

PMID- 7732028
TI  - Regulatory region in choline acetyltransferase gene directs developmental and
      tissue-specific expression in transgenic mice.
AB  - Acetylcholine, one of the main neurotransmitters in the nervous system, is
      synthesized by the enzyme choline acetyltransferase (ChAT; acetyl-CoA:choline O
      acetyltransferase, EC 2.3.1.6). The molecular mechanisms controlling the
      establishment, maintenance, and plasticity of the cholinergic phenotype in vivo
      are largely unknown. A previous report showed that a 3800-bp, but not a 1450-bp,
      5' flanking segment from the rat ChAT gene promoter directed cell type-specific
      expression of a reporter gene in cholinergic cells in vitro. Now we have
      characterized a distal regulatory region of the ChAT gene that confers
      cholinergic specificity on a heterologous downstream promoter in a cholinergic
      cell line and in transgenic mice. A 2342-bp segment from the 5' flanking region
      of the ChAT gene behaved as an enhancer in cholinergic cells but as a repressor
      in noncholinergic cells in an orientation-independent manner. Combined with a
      heterologous basal promoter, this fragment targeted transgene expression to
      several cholinergic regions of the central nervous system of transgenic mice,
      including basal forebrain, cortex, pons, and spinal cord. In eight independent
      transgenic lines, the pattern of transgene expression paralleled qualitatively
      and quantitatively that displayed by endogenous ChAT mRNA in various regions of
      the rat central nervous system. In the lumbar enlargement of the spinal cord, 85
      90% of the transgene expression was targeted to the ventral part of the cord,
      where cholinergic alpha-motor neurons are located. Transgene expression in the
      spinal cord was developmentally regulated and responded to nerve injury in a
      similar way as the endogenous ChAT gene, indicating that the 2342-bp regulatory
      sequence contains elements controlling the plasticity of the cholinergic
      phenotype in developing and injured neurons.

PMID- 7732029
TI  - The antiproliferative activity of c-myb and c-myc antisense oligonucleotides in
      smooth muscle cells is caused by a nonantisense mechanism.
AB  - Smooth muscle cell (SMC) proliferation is thought to play a major role in
      vascular restenosis after angioplasty and is a serious complication of the
      procedure. Developing antisense (AS) oligonucleotides as therapeutics is
      attractive because of the potentially high specificity of binding to their
      targets, and several investigators have reported inhibition of SMC proliferation
      in vitro and in vivo by using AS strategies. We report here the results of our
      experiments on vascular SMCs using AS oligonucleotides directed toward c-myb and
      c-myc. We found that significant inhibition of SMC proliferation occurred with
      these specific AS sequences but that this inhibition was clearly not via a
      hybridization-dependent AS mechanism. Rather, inhibition was due to the presence
      of four contiguous guanosine residues in the oligonucleotide sequence. This was
      demonstrated in vitro in primary cultures of SMCs and in arteries ex vivo. The ex
      vivo model developed here provides a rapid and effective system in which to
      screen potential oligonucleotide drugs for restenosis. We have further explored
      the sequence requirements of this non-AS effect and determined that
      phosphorothioate oligonucleotides containing at least two sets of three or four
      consecutive guanosine residues inhibit SMC proliferation in vitro and ex vivo.
      These results suggest that previous AS data obtained using these and similar,
      contiguous guanosine-containing AS sequences be reevaluated and that there may be
      an additional class of nucleic acid compounds that have potential as
      antirestenosis therapeutics.

PMID- 7732030
TI  - Expression cloning of dSR-CI, a class C macrophage-specific scavenger receptor
      from Drosophila melanogaster.
AB  - Mammalian class A macrophage-specific scavenger receptors (SR-A) exhibit
      unusually broad binding specificity for a wide variety of polyanionic ligands.
      The properties of these receptors suggest that they may be involved in
      atherosclerosis and host defense. We have previously observed a similar receptor
      activity in Drosophila melanogaster embryonic macrophages and in the Drosophila
      macrophage-like Schneider L2 cell line. Expression cloning was used to isolate
      from L2 cells a cDNA that encodes a third class (class C) of scavenger receptor,
      Drosophila SR-CI (dSR-CI). dSR-CI expression was restricted to
      macrophages/hemocytes during embryonic development. When expressed in mammalian
      cells, dSR-CI exhibited high affinity and saturable binding of 125I-labeled
      acetylated low density lipoprotein and mediated its chloroquine-dependent,
      presumably lysosomal, degradation. Although the broad polyanionic ligand-binding
      specificity of dSR-CI was similar to that of SR-A, their predicted protein
      sequences are not similar. dSR-CI is a 609-residue type I integral membrane
      protein containing several well-known sequence motifs, including two complement
      control protein (CCP) domains and somatomedin B, MAM, and mucin-like domains.
      Macrophage scavenger receptors apparently mediate important, well-conserved
      functions and may be pattern-recognition receptors that arose early in the
      evolution of host-defense mechanisms. Genetic and physiologic analysis of dSR-CI
      function in Drosophila should provide further insights into the roles played by
      scavenger receptors in host defense and development.

PMID- 7732031
TI  - Bipartite function of a small RNA hairpin in transcription antitermination in
      bacteriophage lambda.
AB  - Transcription of downstream genes in the early operons of phage lambda requires a
      promoter-proximal element known as nut. This site acts in cis in the form of RNA
      to assemble a transcription antitermination complex which is composed of lambda N
      protein and at least four host factors. The nut-site RNA contains a small stem
      loop structure called boxB. Here, we show that boxB RNA binds to N protein with
      high affinity and specificity. While N binding is confined to the 5' subdomain of
      the stem-loop, specific N recognition relies on both an intact stem-loop
      structure and two critical nucleotides in the pentamer loop. Substitutions of
      these nucleotides affect both N binding and antitermination. Remarkably,
      substitutions of other loop nucleotides also diminish antitermination in vivo,
      yet they have no detectable effect on N binding in vitro. These 3' loop mutants
      fail to support antitermination in a minimal system with RNA polymerase (RNAP),
      N, and the host factor NusA. Furthermore, the ability of NusA to stimulate the
      formation of the RNAP-boxB-N complex is diminished with these mutants. Hence, we
      suggest that boxB RNA performs two critical functions in antitermination. First,
      boxB binds to N and secures it near RNAP to enhance their interaction, presumably
      by increasing the local concentration of N. Second, boxB cooperates with NusA,
      most likely to bring N and RNAP in close contact and transform RNAP to the
      termination-resistant state.

PMID- 7732032
TI  - Maintenance of protective immunity against malaria by persistent hepatic
      parasites derived from irradiated sporozoites.
AB  - Immunization of rodents and humans with irradiation-attenuated malaria
      sporozoites confers preerythrocytic stage-specific protective immunity to
      challenge infection. This immunity is directed against intrahepatic parasites and
      involves T cells and interferon gamma, which prevent development of
      exoerythrocytic stages and subsequent blood infection. The present study was
      undertaken to determine how protective immunity is achieved after immunization of
      rodent hosts with irradiated Plasmodium berghei sporozoites. We present evidence
      that irradiated parasites persist in hepatocytes of rats and mice for up to 6
      months after immunization. A relationship between the persistence of parasites
      and the maintenance of protective immunity was observed. Protective immunity was
      abrogated in irradiated-sporozoite-immunized rats following the application of
      chemotherapy to remove preexisting liver parasites. Additionally, protective
      immunity against sporozoite challenge was established in rats vaccinated with
      early and late hepatic stages of irradiated parasites. These results show that
      irradiation-attenuated sporozoites produce persistent intrahepatic stages in vivo
      necessary for the induction and maintenance of protective immunity.

PMID- 7732033
TI  - Benzene induces gene-duplicating but not gene-inactivating mutations at the
      glycophorin A locus in exposed humans.
AB  - Occupational exposure to benzene is known to cause leukemia, but the mechanism
      remains unclear. Unlike most other carcinogens, benzene and its metabolites are
      weakly or nonmutagenic in most simple gene mutation assays. Benzene and its
      metabolites do, however, produce chromosomal damage in a variety of systems.
      Here, we have used the glycophorin A (GPA) gene loss mutation assay to evaluate
      the nature of DNA damage produced by benzene in 24 workers heavily exposed to
      benzene and 23 matched control individuals in Shanghai, China. The GPA assay
      identifies stem cell or precursor erythroid cell mutations expressed in
      peripheral erythrocytes of MN-heterozygous subjects, distinguishing the NN and N
      phi mutant variants. A significant increase in the NN GPA variant cell frequency
      (Vf) was found in benzene-exposed workers as compared with unexposed control
      individuals (mean +/- SEM, 13.9 +/- 1.7 per million cells vs. 7.4 +/- 1.1 per
      million cells in control individuals; P = 0.0002). In contrast, no significant
      difference existed between the two groups for the N phi Vf (9.1 +/- 0.9 vs. 8.8
      +/- 1.8 per million cells; P = 0.21). Further, lifetime cumulative occupational
      exposure to benzene was associated with the NN Vf (P = 0.005) but not with the N
      phi Vf (P = 0.31), suggesting that NN mutations occur in longer-lived bone marrow
      stem cells. NN variants result from loss of the GPA M allele and duplication of
      the N allele, presumably through recombination mechanisms, whereas NO variants
      arise from gene inactivation, presumably due to point mutations and deletions.
      Thus, these results suggest that benzene produces gene-duplicating mutations but
      does not produce gene-inactivating mutations at the GPA locus in bone marrow
      cells of humans exposed to high benzene levels. This finding is consistent with
      data on the genetic toxicology of benzene and its metabolites and adds further
      weight to the hypothesis that chromosome damage and mitotic recombination are
      important in benzene-induced leukemia.

PMID- 7732034
TI  - Organ and cell allometry in Hawaiian Drosophila: how to make a big fly.
AB  - The importance of body size in predicting many aspects of an animal's biology has
      become well established in recent years. However, little is known about how body
      size evolves at the cellular level. Some published data suggest that it is cell
      number and not cell size that accompanies changes in organ and body size across
      taxa. We examined organ and cell allometry in the wing, eye and basitarsus of
      adult Hawaiian Drosophila, ranging in body length from 0.2 mm to 0.8 mm. Linear
      measurements of all three structures exhibit a positive allometry with body
      length. Exponents of the allometric equation were 0.96, 0.55 and 1.50 for wing,
      eye and basitarsus, respectively. Surface markers were used to quantify cell size
      of each organ. The allometric exponents for cell size as a function of organ size
      were 0.53, 0.68 and 0.33 for wing, eye and basitarsus, respectively. In contrast
      to reports in the literature on other systems, our results for Hawaiian
      Drosophila indicate that cell size may contribute between one third and two
      thirds to evolutionary changes in organ and body size.

PMID- 7732035
TI  - Perception of age in adult Caucasian male faces: computer graphic manipulation of
      shape and colour information.
AB  - This study investigated visual cues to age by using facial composites which blend
      shape and colour information from multiple faces. Baseline measurements showed
      that perceived age of adult male faces is on average an accurate index of their
      chronological age over the age range 20-60 years. Composite images were made from
      multiple images of different faces by averaging face shape and then blending red,
      green and blue intensity (RGB colour) across comparable pixels. The perceived age
      of these composite or blended images depended on the age bracket of the component
      faces. Blended faces were, however, rated younger than their component faces, a
      trend that became more marked with increased component age. The techniques used
      provide an empirical definition of facial changes with age that are biologically
      consistent across a sample population. The perceived age of a blend of old faces
      was increased by exaggerating the RGB colour differences of each pixel relative
      to a blend of young faces. This effect on perceived age was not attributable to
      enhanced contrast or colour saturation. Age-related visual cues defined from the
      differences between blends of young and old faces were applied to individual
      faces. These transformations increased perceived age.

PMID- 7732036
TI  - Expression and activity of the newt Msx-1 gene in relation to limb regeneration.
AB  - The Msx-1 homeobox gene is expressed in various contexts during vertebrate
      development, including the progress zone of the avian and mouse limb bud.
      Expression of mouse Msx-1 in a cultured myogenic cell line conferred a
      transformed phenotype and inhibited fusion into myotubes. It has been proposed
      that Msx-1 expression is required to maintain certain cells in a proliferating
      and undifferentiated state and may be associated with the ability to regenerate
      limbs. Urodele amphibians such as the newt regenerate their limbs by formation of
      a growth zone or blastema, and we have isolated and sequenced newt Msx-1 (NvMsx
      1) from a limb blastemal cDNA library. NvMsx-1 expression was detectable in RNA
      preparations from both limb and tail and their regeneration blastemas, although
      cultured cells established from limb blastemal mesenchyme gave negative results.
      When either COS cells or cultured newt blastemal cells were cotransfected with an
      expression vector for NvMsx-1 and reporter plasmids containing multiple homeobox
      protein binding sites, NvMsx-1 repressed reporter expression. If NvMsx-1 was
      expressed together with a marker enzyme in cultured newt blastemal cells, no
      significant difference in DNA synthesis was observed relative to control
      transfectants. When myogenic mononucleate cells were transfected with NvMsx-1 and
      subsequently exposed to low serum to promote fusion, the fraction of Msx-1
      positive cells in myotubes was comparable to a control transfected population
      analysed in the same culture. These results indicate that although Msx-1
      expression could be important for limb regeneration, it does not exert a cell
      autonomous effect on proliferation or myogenic differentiation of cultured
      blastemal cells.

PMID- 7732037
TI  - A minimal model for T-cell vaccination.
AB  - We have developed a mathematical model for the regulation of the growth of
      autoreactive T cells (the T cells responsible for autoimmunity). The model is
      very simple in that it is based only on the fundamental properties of T cells.
      However, despite this simplicity, it can account for a variety of phenomena
      referred to as T-cell vaccination. The purpose of T-cell vaccination is to create
      resistance to autoimmunity. This can be achieved by injecting either a
      subpathogenic quantity of autoreactive T cells, or attenuated autoreactive cells,
      or cells that recognize the autoreactive cells. The results of our model are
      based on the assumption that the self antigens involved in T-cell vaccination are
      normally not expressed; thus the autoreactive T lymphocytes are neither activated
      nor negatively selected. Self tolerance, therefore, corresponds to a 'passive'
      state. T-cell vaccination induces a transition from this passive state of
      tolerance to an active state of tolerance. In this state the autoreactive cells
      are controlled by regulator cells which recognize the autoreactive cells. The
      model predicts a qualitative difference between vaccination with normal
      autoreactive cells and vaccination with attenuated autoreactive cells. Normal
      cells may give rise to a permanent switch to the vaccinated state; attenuated
      cells, however, can provide only transient protection, which is dose dependent.
      Preliminary experimental data confirm this prediction. Finally, we propose a
      speculative explanation for relapsing autoimmune disease.

PMID- 7732038
TI  - Blocking the phase-shifting effect of neuropeptide Y with light.
AB  - Previous studies have indicated that the neuropeptide Y input from the
      intergeniculate leaflet of the lateral geniculate nucleus to the suprachiasmatic
      nucleus is the final part of a non-photic phase shifting pathway to pacemakers in
      hamsters, or that neuropeptide Y is necessary for other pathways to be effective.
      Experiments in which two stimuli are presented during the same circadian cycle
      have shown that phase shifts in response to at least two non-photic stimuli are
      attenuated by a subsequent light pulse during the subjective day. This study was
      conducted to investigate the neural site of the blocking effect of light on non
      photic stimuli. Experiment 1 showed that phase shifts in response to induced
      wheel-running during the subjective day are greatly attenuated by a subsequent
      light pulse. Experiment 2 showed that phase shifts in response to injections of
      neuropeptide Y in the middle of the subjective day were also greatly reduced by a
      subsequent light pulse. These results provide some insight about the site of the
      blocking action of light on non-photic phase shifts. Because there is evidence
      indicating that neuropeptide Y may mediate phase shifts in response to induced
      activity, and because light was able to block phase shifts produced by
      neuropeptide Y, we conclude that, in blocking activity-induced shifts, light must
      act downstream from the release of neuropeptide Y into the suprachiasmatic
      nucleus.

PMID- 7732039
TI  - Evidence for a sex-segregated migration in the humpback whale (Megaptera
      novaeangliae).
AB  - Existing population models for humpback whales assume that all individuals within
      a population undertake the annual migration from feeding areas in high latitudes
      to breeding areas in tropical waters. An excess of males was recorded in the
      commercial whaling catches near breeding areas in the southern hemisphere, but no
      account of this was taken in developing population models, because it was
      believed that this bias was a result of whalers selecting against females with
      young calves. Here we demonstrate that the sex ratio of migrating humpback whales
      near a breeding area is highly skewed towards males. A biopsy study carried out
      in 1992 throughout the northward and southward migrations revealed a sex ratio of
      2.4 males: 1 female in the population of humpback whales migrating along the east
      Australian coast (n = 180). A reanalysis of the catches made during commercial
      whaling in this and other areas of the southern hemisphere gave a sex ratio of
      the same order. The most plausible explanation, supported by some evidence, is
      that some females remain in the feeding areas throughout winter. The results
      reported here show that existing management models require major revision to take
      account of these findings.

PMID- 7732041
TI  - [Nursing: multicultural crossroads. A challenge for the nurses of the third
      millennium].

PMID- 7732040
TI  - [Group processes: a theoretical search].

PMID- 7732042
TI  - [Organization of work as an organic process in a sector which produces offers of
      service].

PMID- 7732043
TI  - [Health workers and the Division of Infective Diseases of the U.S.S.L. 47 in
      Mantova from 1973 to 1992: how to eliminate erroneous beliefs].

PMID- 7732044
TI  - [Permanent education a priority instrument in the organizational transition of
      the health services].

PMID- 7732045
TI  - [Patients with multiple injuries. Aid outside the hospital].

PMID- 7732046
TI  - Pharmacokinetic drug interactions. Part 1: Drugs A-C.

PMID- 7732047
TI  - Synthesis and biological activity of pyrimidobenzodiazepine derivatives. New ring
      systems: triazolo- and tetrazolo-pyrimido-benzodiazepines.
AB  - New triazolo- and tetrazolo-pyrimidobenzodiazepines were synthesized and screened
      as anti-HIV, anticancer and immunosuppressive agents. Some of the compounds
      showed immunosuppressive activity, similar to or stronger than that of
      cyclosporine A.

PMID- 7732048
TI  - Determination of aprindine in human plasma using reversed phase HPLC.
AB  - A rapid, simple, accurate method is presented for the determination of aprindine
      in human plasma. Liquid-liquid extraction of aprindine was carried out using
      diethyl ether. Amiodarone was applied as an internal standard. The samples were
      chromatographed on LiChrosorb RP-18 (10 microns) column and the mobile phase was
      methanol/acetonitrile/phosphate buffer pH 2.5 (80:15:5). The detection was
      carried at 254 nm. The method was tested for linearity (range from 0.5 to 2.5
      micrograms/ml), recovery (ca. 90%) and precision (CV = 3.7%).

PMID- 7732049
TI  - Fatty acids from cod-liver oil as skin penetration enhancers.
AB  - A fatty acid extract is discharged during the refining of medicinal cod-liver
      oil. The fatty acid composition of the extract was determined and it was found to
      contain an vast variety of fatty acids. About 17% of the fatty acids consisted of
      saturated fatty acids, the rest was unsaturated fatty acids. The extract was an
      effective transdermal penetration enhancer and this effect was found to be
      associated with the unsaturated portion of fatty acids.

PMID- 7732050
TI  - [Hydrophobic modification of polyelectrolytes as solubility enhancers in
      preparations for parenteral administration].
AB  - Up to now there is no excipient for the solubilization of poorly watersoluble
      drugs that can be used without limitations in pharmaceutical preparations for
      intravasal application. The available surfactants show considerable hemolytic
      activity, cause anaphylactic reactions are chemically instable or have no
      sufficient solubilizing capacity. By polymerisation of non-ionic surfactants
      amphiphilic side-chain-polymers are obtained which show in vitro the same
      solubilization capacity as the monomers but exhibit practically no hemolytic
      activity. The objective of this work was to investigate, if this findings are
      also true for ionic oligomers. For this purpose, polyacrylic acids were
      substituted with long-chain alkyl amines. The solubilization capacity of these
      oligomers exceeds that of non-ionic amphiphilic side-chain-polymers and that of
      other surfactants. The hemolytic activity of the oligomers was below that of
      common ionic surfactants. The solubilization capacity as well as the hemolytic
      activity depends on the oligomers degree of substitution. Considering their high
      solubilization capacity and their low hemolytic activity, these oligomers may be
      excipients in preparations for parenteral application.

PMID- 7732051
TI  - [Biotransformation of (+)-methamphetamine in fertile hen's eggs].
AB  - On application of (+)-methamphetamine (1) to the albumen of embryonated hen's
      eggs it is possible to detect phase I as well as phase II metabolites of 1 in the
      allantois liquid. When application is effected on the first day of incubation,
      methamphetamine is less toxic than when effected on the sixth day of incubation.
      Besides unchanged 1 ten metabolites have been identified. Principal pathways of
      biotransformation are N-dealkylation as well as aromatic p-hydroxylation and--as
      phase II reactions--N-acetylation and other conjugation reactions. The total
      amount of the metabolites produced depends on time of incubation and is up to
      about 25% of the applied dose. Differences from, but also similarities to human
      metabolism have been noticed. Consequently, the experiment is likely to be
      suitable as an alternative method for testing biotransformation reactions.

PMID- 7732052
TI  - [Biotransformation processes in fertile hen's eggs. 1. Metabolic transformation
      of 7-ethoxycoumarin].
AB  - An alternative method for the investigation of biotransformations employing
      fertile chicken eggs has been developed. In these studies, solutions of 7
      ethoxycoumarin were injected into the white of eggs from a standardized breed
      after brooding time of at least 8 days. After further incubation, the allantois
      was analyzed for metabolites of 7-ethoxycoumarin. The dealkylated metabolite of 7
      ethoxycoumarin, namely 7-hydroxycoumarin, could be assayed in the allantois
      liquid by means of a new HPLC method. Furthermore, conjugates of 7
      hydroxycoumarin, namely the glucuronid and the sulfate, can be detected
      indirectly in the allantois after conjugate cleavage. The inducability of the
      cytochrome P-450-dependent O-dealkylation has been studied with phenobarbital and
      3-methylcholanthrene. An increase in the conversion of 7-ethoxycoumarin to 7
      hydroxycoumarin was observed after addition of 3-methylcholanthrene. The detected
      metabolites demonstrate the usefulness of the developed model for studying
      biotransformation processes.

PMID- 7732053
TI  - Circadian-time rhythm of hepatic protein kinase C of rats pretreated with
      phenobarbital.
AB  - Circadian-time dependent differences of protein kinase C (PKC) activities as well
      as its susceptibility to a phenobarbital caused suppression in vivo (40 mg/kg
      b.i.d. for 3 days) were studied in outbred male Wistar rats weighing 280-360 g.
      The well-known phenobarbital induction of cytochrome P-450 and 7-pentylresorufin
      O-depentylase (PROD) was associated with inhibition of the hepatic PKC. The
      activities of the cytosolic and membrane-bound PKC were significantly lower than
      in the respective controls. Statistically significant circadian-time differences
      were found. The activities of both cytosolic and membrane-bound PKC of control
      rats were highest in the evening (158% and 131%, respectively, of the morning
      values). Furthermore, phenobarbital inhibited the enzyme more strongly at 19.00 h
      than at 07.00 h. Our results suggest that increase of hepatic cytochrome P-450
      content as well as induction of PROD are inversely related with the function of
      PKC.

PMID- 7732054
TI  - Sensitivity of the DNA polymerase activities of Tetrahymena pyriformis to
      cytosine arabinoside triphosphate and N-ethyl-maleiimide.
AB  - Two DNA polymerase activities from Tetrahymena pyriformis were studied. The
      cytoplasmic polymerase was inhibited by cytosine arabinoside triphosphate (ara
      CTP) and N-ethylmaleiimide (NEM) whereas the nuclear enzyme was not inhibited by
      araCTP and was inhibited by NEM to a lesser extent. The two enzymes could use
      CsCl, NaCl, and LiCl instead of KCl to varying degrees in the polymerase
      reaction. The two activities showed optimum activity at different concentrations
      of NaCl and KCl.

PMID- 7732055
TI  - Role of aliphatic acids in the biosynthesis of vermiculin in penicillium
      vermiculatum.
AB  - The diolode macrolide vermiculin (1) together with the three unsaturated
      aliphatic ketoacids vermiculinic (2), vermiculic (3) and 4-deoxovermiculic acid
      (4) were isolated from the cultivation broth of Penicillium vermiculatum.
      Biotransformation of 2 and 3 with growing and resting cells of P. vermiculatum
      was studied. We suppose, that 2 which is formed from 3, is the ultimate
      progenitor of 1.

PMID- 7732056
TI  - [Instructions to German hospital pharmacists in the 19th century].
AB  - Nine instructions for hospital pharmacists from the nineteenth century were
      investigated. They show the pharmacist's responsibility for drug quality and the
      observance of all legal requirements. He had usually no economical competences.
      Laboratory investigations and food research were common pharmaceutical tasks. To
      a great extent, the pharmacist had to deal with accounting and book-keeping.

PMID- 7732057
TI  - Structure-activity relationship studies of CNS agents, Part 20: 9-(omega-[1-(m
      chlorophenyl)-4-piperazinyl]alkyl]-1,2,3,4-tetra-hydro- beta-carbolines: new 5
      HT1A and 5-HT2A receptor ligands.

PMID- 7732058
TI  - Mannich bases of 2-arylmethylenecyclohexanone with cytotoxic activity.

PMID- 7732059
TI  - Synthesis and antimicrobial activity of novel aminopyrimidinedione and
      aminothiazolidindione derivatives.

PMID- 7732060
TI  - A fascile synthesis and central nervous system activities of fluorine containing
      spiro-[3 H-indole-3,4'(4H)-pyran]-2(1H)-ones.

PMID- 7732061
TI  - Binding of pirprofen with serum albumin obtained from uremic patients.

PMID- 7732062
TI  - Evidence for antibiotics in the two Algerien truffles Terfezia and Tirmania.

PMID- 7732063
TI  - Interpersonal relationships between the nurses and the doctors, professional
      performance and quality of care.

PMID- 7732064
TI  - Ethical responsibilities of the nurse.

PMID- 7732065
TI  - The relationship between holistic care and therapeutic healing.

PMID- 7732066
TI  - A fast method to compute surface potentials generated by dipoles within
      multilayer anisotropic spheres.
AB  - Berg and Scherg's fast computation method is extended to multilayer anisotropic
      spheres. The Berg parameters can be dependent upon a dipole radial parameter or
      not, depending on the actual sphere conductivities and the layer the dipole is
      within. To find the Berg parameters, no specific electrode locations are
      required. Berg and Scherg's method is generally applicable whenever de Munck and
      Peters's addition-subtraction method can be used.

PMID- 7732067
TI  - A Monte Carlo estimation of tissue optical properties for use in laser dosimetry.
AB  - In certain clinical situations, such as photodynamic therapy, light dosimetry
      should be considered. The propagation of light in tissues is influenced by
      fundamental or microscopic optical properties, namely absorption mu a and
      scattering mu s coefficients, refractive index n and anistropy factor g. These
      optical parameters can be determined experimentally by direct and/or indirect
      methods when tissue macroscopic properties, such as reflectance, transmittance or
      collimated transmittance from a tissue slab, are measured. The method described
      in this work provides graphical, and in simple cases analytical, 'inverse'
      solutions to determine tissue microscopic properties from measured macroscopic
      parameters. The graphs necessary for this inversion have been calculated and are
      provided. The method can be applied in either direct or indirect techniques and
      it does not depend on limitations introduced by assumptions and approximations
      when using theoretical models. It can also be applied for any tissue type,
      detector geometry and experimental apparatus. The accuracy of the method is very
      good over a wide range, unlimited in practice, of values of optical properties.
      Finally, the results of this work are in good agreement with theoretical and
      experimental results of other investigators.

PMID- 7732068
TI  - Validation of a dose-point kernel convolution technique for internal dosimetry.
AB  - The objective of this study was to validate a dose-point kernel convolution
      technique that provides a three-dimensional (3D) distribution of absorbed dose
      from a 3D distribution of the radionuclide 131I. A dose-point kernel for the
      penetrating radiations was calculated by a Monte Carlo simulation and cast in a
      3D rectangular matrix. This matrix was convolved with the 3D activity map
      furnished by quantitative single-photon-emission computed tomography (SPECT) to
      provide a 3D distribution of absorbed dose. The convolution calculation was
      performed using a 3D fast Fourier transform (FFT) technique, which takes less
      than 40 s for a 128 x 128 x 16 matrix on an Intel 486 DX2 (66 MHz) personal
      computer. The calculated photon absorbed dose was compared with values measured
      by thermoluminescent dosimeters (TLDS) inserted along the diameter of a 22 cm
      diameter annular source of 131I. The mean and standard deviation of the
      percentage difference between the measurements and the calculations were equal to
      -1% and 3.6%, respectively. This convolution method was also used to calculate
      the 3D dose distribution in an Alderson abdominal phantom containing a liver, a
      spleen, and a spherical tumour volume loaded with various concentrations of 131I.
      By averaging the dose calculated throughout the liver, spleen, and tumour the
      dose-point kernel approach was compared with values derived using the MIRD
      formalism, and found to agree to better than 15%.

PMID- 7732069
TI  - A method of obtaining the Awall correction factor of an ionization chamber in a
      60Co gamma-ray beam using tissue-air ratio data.
AB  - A method is reported that evaluates the wall correction factor (Awall)water of an
      ionization chamber using measured data. The method needs a revised type of tissue
      air ratio (TARcav) that should be measured with the ionization chamber. An
      experimental study has been carried out for 60Co gamma-rays using zero-area
      TARcav data extrapolated from non-zero-area TARcav data using the extrapolation
      method developed by Bjarngard and Petti. Using this technique, it is found that
      the value of (Awall)water for an ionization chamber has a deviation of -0.1% to 
      0.4% as compared with the Monte Carlo results. An experimental study has also
      been carried out using a published set of 60Co traditional tissue-air ratio (TAR)
      data assuming TARcav = TAR.

PMID- 7732070
TI  - Beam data measurements for dynamic wedges on Varian 600C (6 MV) and 2100C (6 and
      10 MV) linear accelerators.
AB  - The measurement of beam data for dynamic wedge dosimetry requires the integration
      of radiation dose at points across the radiation field during the dose delivery.
      The different measurement techniques required when using a linear diode array to
      measure beam profiles and when using ionization chambers to measure depth doses
      and effective wedge factors are described. The segmented treatment tables (STTS),
      which specify the delivered dose as a function of jaw position, are used by the
      control algorithm to deliver dynamic wedge fields. The reproducibility achieved
      using STTS is very consistent (and the stability of the accelerators is very
      good) so there is no significant variation in effective wedge factor or profile
      shape. There is a unique set of 132 STTS for each energy and design of treatment
      machine, which encompasses all the dynamic wedge data. There are significant
      discontinuities of up to 14% in wedge factors at certain field sizes. This means
      that wedge factors have to be measured at small increments (0.5 cm) in field
      size, as it is the width of the dynamic wedge field that determines the STT used.
      Considerable care must be taken when implementing these data on a current
      generation treatment planning computer.

PMID- 7732071
TI  - In vivo XRF analysis of mercury: the relation between concentrations in the
      kidney and the urine.
AB  - The objective of this study was to determine the concentrations of mercury in
      organs of occupationally exposed workers using in vivo x-ray fluorescence
      analysis. Twenty mercury exposed workers and twelve occupationally unexposed
      referents participated in the study. Their mercury levels in kidney, liver and
      thyroid were measured using a technique based on excitation with partly plane
      polarized photons. The mercury levels in blood and urine were determined using
      atomic absorption spectrophotometry. The detection limit for mercury in the
      kidney was exceeded in nine of the exposed workers, but in none of the referents.
      The mean kidney mercury concentration (including estimates below the detection
      limits) was 24 micrograms g-1 in the exposed workers, and 1 microgram g-1 in the
      referents. The association between mercury in the kidney and in urine was
      statistically significant, but it was unclear whether the relation was linear.
      The measurements on liver (n = 10) and thyroid (n = 8) in the exposed workers
      showed mercury levels below the detection limit. The study shows that it is now
      possible to measure the mercury concentrations in kidneys of occupationally
      exposed persons, using in vivo x-ray fluorescence. The estimated concentrations
      are in reasonable agreement with the limited human autopsy data, and the results
      of animal studies.

PMID- 7732072
TI  - The experimental evaluation of a prototype rotating slat collimator for planar
      gamma camera imaging.
AB  - A collimator consisting of a series of parallel slats has been constructed and
      used in conjunction with a conventional gamma camera to collect one-dimensional
      projections of the radioisotope distribution being imaged. With the camera
      remaining stationary, the collimator was made to rotate continuously over the
      face of the detector and the projections acquired were used to reconstruct a
      planar image by the theory of computed tomography. The propagation of noise on
      image reconstruction was largely offset by the increased geometric efficiency
      that resulted from the enlarged solid angle of acceptance afforded by the slat
      collimator. For a uniform disc of activity the signal to noise ratio (SNR) at a
      point in an image reconstructed by convolution and backprojection is shown to be
      given by [formula:see text] and Q1(xi) is the one-dimensional filter function in
      Fourier space. Improved noise behaviour was observed for images acquired with the
      slat collimator compared to those acquired with a low-energy high-resolution
      (LEHR) collimator for small distributions of activity. Spatial resolution with
      the slat collimator was approximately equal to that obtained with an LEHR
      collimator and improved contrast was observed in images of small hot regions.

PMID- 7732073
TI  - Automatic registration of SPECT images as an alternative to immobilization in
      neuroactivation studies.
AB  - Subtraction of the two components (baseline and stimulation) of a neuroactivation
      study using 99Tcm HMPAO SPECT requires accurate registration of the two images.
      Immobilization of the subject during and between the two components of the study
      can prove difficult and degrades signal to noise ratio. The use of an automated
      image registration technique for registering the two components of the test can,
      even in the case where the subject is removed from the scanner, produce
      significantly better registration than immobilization.

PMID- 7732074
TI  - Monitor unit calculation for large wedged high-energy photon beams.
AB  - With the modern high-energy linear accelerators, the following beam
      characteristics have to be taken into account in the monitor unit (MU)
      calculation of a wedged treatment: (i) the field size dependence of wedge
      factors; (ii) the changes in depth dose and maximum build-up depth (dmax) induced
      by wedges; and (iii) the field size dependence of dmax. The incorporation of a
      field size specific wedge factor in an MU calculation is straightforward. Effects
      (ii) and (iii) however, often cause confusion and inconsistency in the choices of
      the reference depth for wedge factors and the normalization depth for wedged
      depth dose, and consequently can lead to inconsistent MU calculation formalism
      with additional efforts of up to 7% in the delivered dose. In this note, we
      illustrate a derivation of an exact central axis MU calculation for wedged
      treatments, which correctly accounts for the effects mentioned above.

PMID- 7732076
TI  - Pharmacology and physical therapy.

PMID- 7732075
TI  - Comments on the article "Photoelectron bremsstrahlung--analytical
      possibilities?".

PMID- 7732077
TI  - Special series on pharmacology and physical therapy.

PMID- 7732078
TI  - Basic pharmacokinetics and the potential effect of physical therapy interventions
      on pharmacokinetic variables.
AB  - Pharmacokinetics involves the factors that influence drug absorption,
      distribution, and elimination. Pharmacokinetic variables determine how a specific
      dose of a drug will eventually reach target tissues and exert a response. Various
      factors can influence normal pharmacokinetics, including exercise, application of
      physical agents, and massage. These interventions produce hemodynamic and other
      physiologic changes that can potentially alter drug disposition within the body.
      The magnitude and specific type of pharmacokinetic changes, however, are highly
      variable depending on the specific intervention and the drug in question.
      Physical therapy interventions seem to have the greatest potential to affect
      absorption and distribution of drugs that are administered by transdermal
      techniques or by subcutaneous and intramuscular injections. Research is needed to
      determine exactly how physical therapy interventions can affect the
      pharmacokinetics of various medications, and how the clinical effects of these
      medications are affected by altered drug disposition.

PMID- 7732079
TI  - The effects of intrathecally administered baclofen on function in patients with
      spasticity.
AB  - The purpose of this article is to review the literature on the effects of
      intrathecally administered baclofen on impairment in spasticity and muscle
      activation patterns, on functional limitations in mobility and self-care, and on
      disability in daily life roles. We found plentiful evidence of improvement in
      spasticity, spasms, and bladder function and some reports of improved patterns of
      muscle activation and kinematics of single-joint movement. Improved ability to
      accomplish transfers, self-care, and locomotion is less consistently studied but
      has also been reported in about 60% to 70% of patients. Evidence of improved
      quality of life is primarily anecdotal but may be found in 10% to 30% of
      patients. We conclude that research protocols should be developed to clarify
      effects on control of voluntary movement, functional limitations, and quality of
      life.

PMID- 7732080
TI  - Pharmacological and nonpharmacological interventions in the treatment of
      Parkinson's disease.
AB  - Parkinson's disease is a neurodegenerative disorder of older persons that
      eventually leads to disability. It is characterized by tremor, rigidity,
      bradykinesia, and postural instability. Progressive stages can be identified,
      each with unique problems. The optimal management of Parkinson's disease requires
      multiple professionals to address the needs of the patients as well as those of
      the caregivers. In addition to pharmacologic management, patients with
      Parkinson's disease can benefit from physical intervention and psychological
      support. This article summarizes strategies incorporating the multiple
      disciplines for each stage of the disease. [Cutson TM, Laub KC, Schenkman M.
      Pharmacological and nonpharmacological interventions in the treatment of
      Parkinson's disease.

PMID- 7732081
TI  - Patient-controlled analgesia: a method for the controlled self-administration of
      opioid pain medications.
AB  - The purposes of this article are to introduce the reader to patient-controlled
      analgesia (PCA) and to summarize its use in several selected pain-related
      conditions. patient-controlled analgesia is a relatively new technique for
      managing pain in which patients are able to self-administer small doses of opioid
      analgesic medications when needed. The authors briefly review some of the
      problems associated with current and previous opioid delivery strategies and
      highlight the advantages of PCA over these other methods. They then discuss the
      components of the PCA system and briefly describe how the system is operated and
      controlled. In this discussion, the authors indicate an appropriate therapeutic
      goal and suggest knowledge requirements for the effective use of PCA. The authors
      close with a brief summary of several reports describing the use of PCA in the
      management of postoperative pain, cancer pain, and pain associated with labor and
      delivery. Indications and contraindications for use in these conditions are
      presented. Because physical therapists often play a major role in pain
      management, it is important for them to be well informed with regard to recent
      developments in this rapidly developing area of clinical practice.

PMID- 7732082
TI  - The role of Army physical therapists as nonphysician health care providers who
      prescribe certain medications: observations and experiences.
AB  - For two decades, Army physical therapists have been granted limited privileges to
      prescribe certain medications when serving as nonphysician health care providers
      for the primary evaluation and treatment of patients with neuromusculoskeletal
      dysfunctions. A brief summary of the events that led to this physician-extender
      role is presented. This article describes the Army regulations, credentialing
      process, and expanded clinical privileges developed to prepare and support
      physical therapists working as primary neuromusculoskeletal screeners who are
      credentialed to order certain pharmacologic medications. A historical synopsis of
      Army physical therapists ordering pharmacologic medications. A historical
      synopsis of Army physical therapists ordering pharmacologic medications in their
      expanded role as nonphysician health care providers is also presented. Results of
      a 1994 Army-wide survey of physical therapy clinics are provided in terms of
      medications prescribed and observations by those involved. The educational
      opportunities designed to ensure safe and appropriate uses of these privileges
      are described.

PMID- 7732083
TI  - Effects of cardiovascular medications on exercise responses.
AB  - Many patients who are referred for physical therapy take medications that affect
      either their physiological responses to exercise or their ability to exercise.
      The purpose of this article is to discuss how medications potentially can affect
      cardiovascular responses to exercise. The effects of selected medications on
      heart rate, blood pressure, and electrocardiographic responses during exercise;
      on exercise performance; and on training adaptations are discussed. The types of
      medications included in this review are beta-adrenergic receptor antagonists,
      vasodilators, diuretics, digitalis, and antiarrhythmic agents. The mechanisms of
      action and the clinical indications are described for each category of drugs.
      Ways in which each of the categories of drugs interacts with exercise responses,
      exercise performance, and training adaptations are described. Knowledge of a
      person's medications can provide valuable information on current physical
      condition and medical history and can alert therapists as to how exercise
      responses may be altered. Potential complications that are likely to occur during
      exercise can be identified, facilitating the design of safe and effective
      treatment programs.

PMID- 7732084
TI  - Pulmonary medications.
AB  - Many of the patients seen by physical therapists have primary or secondary
      diagnoses for which cardiovascular- or pulmonary-active medications may be
      prescribed. There is a need, therefore, for physical therapists to understand the
      pharmacologic treatment of such patients. This article discusses medications
      commonly used in the treatment of pulmonary disorders. These medications are
      typically divided into the following categories: bronchodilators, anti
      inflammatory agents, decongestants, antihistamines, antitussives, mucokinetics,
      respiratory stimulants and depressants, and paralyzing and antimicrobial agents.
      Regardless of which group a particular medication belongs to, the rationale for
      its prescription centers on promoting bronchodilation or relieving
      bronchoconstriction, facilitating the removal of secretions from the lungs,
      improving alveolar ventilation or oxygenation, or optimizing the breathing
      pattern. The relative importance of each of these goals depends on the specific
      disease process involved and the resultant respiratory problem(s).

PMID- 7732085
TI  - Pharmacologic management of hyperglycemia in diabetes mellitus: implications for
      physical therapy.
AB  - Diabetes mellitus is a costly, chronic disease that affects millions of Americans
      each year. The classic triad of diabetes management includes diet, exercise, and
      pharmacological intervention. A variety of complications may result due to this
      chronic disease, and manipulation of the triad of treatment factors may be
      necessary in order to effectively treat the individual patient. Physical
      therapists are consulted in both the primary care of patients with diabetes and
      in the case of complications; therefore, an understanding of the various forms of
      the disease, the complications, and the treatment approaches is necessary for
      comprehensive patient management. The purposes of this article are to give an
      overview of the disease and its common complications and to discuss the various
      treatment approaches with emphasis on the pharmacological interventions and
      physical therapy concerns.

PMID- 7732086
TI  - Ergogenic aids.
AB  - In the context of sport, an ergogenic aid can be broadly defined as a technique
      or substance used for the purpose of enhancing performance. Ergogenic aids have
      been classified as nutritional, pharmacologic, physiologic, or psychologic and
      range from use of accepted techniques such as carbohydrate loading to illegal and
      unsafe approaches such as anabolic-androgenic steroid use. The efficacy of many
      of these techniques is controversial, whereas the deleterious side effects are
      clear. The purpose of this article is to review the epidemiology, administration,
      efficacy, pharmacology, and side effects of commonly used ergogenic aids.
      Physical therapists should be able to recognize the signs of ergogenic aid abuse
      in individuals under their care, and they should be aware of the side effects of
      these aids. Moreover, the physical therapist can serve as a resource for those
      individuals seeking information on the risks and benefits of ergogenic aids.

PMID- 7732087
TI  - Human resources.

PMID- 7732088
TI  - When things aren't what they seem.

PMID- 7732089
TI  - President's message: the challenges ahead.

PMID- 7732090
TI  - Endoscopic augmentation mammoplasty: the umbilical approach.
AB  - Endoscopy, which has allowed surgeons to look into the body as never before, has
      recently been used for breast enlargements, a procedure accomplished through an
      umbilical approach. Plastic surgical nurses are key members of the surgical team
      involved in this procedure, and need to participate in educating patients about
      this new technology. This article will examine endoscopic augmentation
      mammoplasty (the umbilical approach) and the nurse's role in its practice.

PMID- 7732091
TI  - The care and feeding of microvascular flaps: how nurses can help prevent flap
      loss.
AB  - Free flaps are used to reconstruct defects that cannot be repaired by traditional
      methods using local adjacent tissue. Advantages include a single operation,
      decreased immobility, increased vascular supply to tissues for healing, minimal
      risk of flap loss, and primary closure of the donor site. Disadvantages are a
      long operation, two surgical sites, need for surgery if vascular compromise
      occurs, donor site morbidity, and expense. Preoperative care focuses on readiness
      for surgery and avoidance of medications (nicotine, caffeine) and situations
      (cold exposure) that cause vasospasm. Intraoperative nursing care includes
      positioning, range of motion, and pneumatic compression devices for the long
      case. The operating microscope requires special care and instruments. After
      surgery, blood flow to the flap is closely monitored. Laser flow Doppler can be
      used with data recorded on a flow sheet. Common postoperative problems include
      temperature instability, pain, blood pressure fluctuations, and oliguria.
      Dismissal teaching includes avoidance of vasoconstrictive medications and
      dressing changes.

PMID- 7732092
TI  - Product line management: can it work for plastic surgery?
AB  - Health care managers are looking to other industries for assistance in designing
      strategies to respond to changing environments. In the evolving environment of
      managed care, operational success depends on successful management of fiscal
      resources. Product line management can be a key component of organizational
      response to change. This article describes the successful implementation of a
      product line management program at a large Midwestern hospital, and presents
      advice to plastic surgical nurses to undertake in their own facilities.

PMID- 7732093
TI  - Psychoactive substance disorders among health care professionals.
AB  - Alcohol and drugs are involved in many cases requiring action against nurses and
      other health care professionals. Nurses are likely to be polydependent. Older
      nurses tend to use more alcohol and prescription drugs; younger nurses more
      likely use marijuana and cocaine. The supervisor of an abusing nurse is guided by
      the job performance standard and constructive confrontation. Every agency should
      have clear policies on substance abuse, so these policies can be implemented not
      created for the employee. Rehabilitation programs include inpatient and
      outpatient designs. The 12-step self-help group participation is most common.

PMID- 7732094
TI  - Recruitment, hiring and orientation: investing in the future.

PMID- 7732095
TI  - Taking the O.R. to the office--planning ahead for emergencies.

PMID- 7732096
TI  - Surgical Safari: a program for children and their parents.

PMID- 7732097
TI  - Reliability and validity.

PMID- 7732098
TI  - AIDS dementia complex.

PMID- 7732099
TI  - Metastatic skin disease in an immunocompromised patient.

PMID- 7732100
TI  - Smoking: adverse effects on outcomes for plastic surgical patients.
AB  - Smoking is known to have a potentially adverse effect on the outcomes of plastic
      surgical procedures and, in particular, on wound healing. Numerous clinical
      studies have substantiated that cigarette smokers are at increased risk for wound
      healing problems. Cigarette smoke contains a number of toxic products. Of these
      toxins, nicotine has been studied in detail and is known to inhibit macrophages
      and fibroblasts, potentiate vascular thrombosis, and cause vasoconstriction.
      Carbon monoxide combines with hemoglobin to form carboxyhemoglobin, which reduces
      oxygen availability to tissues. When operating on cigarette smokers a few options
      exist that may improve outcomes: less undermining with rhytidectomy; sympathetic
      blockades; limited use of alternate nicotine sources; and of course smoking
      cessation, which is ideal.

PMID- 7732101
TI  - Aesthetic facial reconstruction: blending human perception and the facial subunit
      theory.
AB  - Facial reconstructive surgical results play a key role in how an individual
      accepts themselves and how society accepts the individual. Surgeons must strive
      to create the most aesthetic results, which includes reestablishing the expected
      contours, highlights, and landmarks. By understanding the subunits theory,
      plastic surgical nurses can provide patients with knowledgeable preoperative
      teaching, and can better anticipate the scope and necessary equipment for each
      reconstruction.

PMID- 7732102
TI  - Munchausen syndrome: hospital hobo of the 1990s.
AB  - Munchausen Syndrome is an unusual subset of symptoms experienced by patients who
      self-inflict artificial illness. Caring for Munchausen patients, who are
      frequently finding their way into plastic surgery practices, is very time
      consuming because they often fail to respond to standard modalities of treatment.
      They abuse the medical system by seeking care from one or more caregivers at the
      same time and appear to relish repeating expensive diagnostic procedures. Four
      case studies are presented in this article along with suggestions for treating
      these patients.

PMID- 7732103
TI  - Operation Smile International: missions of mercy.
AB  - Operation Smile International (OSI) was formed in 1983 to provide underprivileged
      children in developing countries and the United States with common surgical
      procedures such as cleft lip, cleft palate, and burns, and to provide education
      to health care professionals in those countries. Over 11 years, OSI has aided
      over 20,000 children in 11 countries, and has grown into an organization of
      thousands of volunteers.

PMID- 7732104
TI  - Pain-free harvesting of skin grafts with EMLA.
AB  - This article will describe EMLA, a new type of topical anesthetic that is
      versatile in its clinical use, is effective in relieving pain, and has minimal,
      if any, side effects. Patient and staff education in the use of EMLA can help
      relieve the patient's anxiety about the pain from surgery and result in a
      positive outcome, including enhanced wound healing.

PMID- 7732105
TI  - Facility accreditation--stacking the odds in your favor.

PMID- 7732106
TI  - Patient education in practice settings: a candid discussion with plastic surgical
      nurses.

PMID- 7732107
TI  - Patient positioning during surgical procedures.

PMID- 7732108
TI  - Data analysis.

PMID- 7732109
TI  - Facial reconstruction with prefabricated induced expanded (PIE) supraclavicular
      skin flaps.
AB  - The prefabricated induced expanded (PIE) supraclavicular flap refers to the
      staged transfer of an expanded supraclavicular skin with a fascia flap used as
      the carrier. In three patients, we utilized PIE supraclavicular flaps to
      successfully reconstruct a total forehead and two major nasal defects. Our first
      PIE flap confirmed the feasibility of the method but necessitated two
      microvascular free flaps. In the ensuing two patients, we reduced the need for
      microvascular anastomoses by using simple pedicled flap transfers in either or
      both stages. Whenever feasible, the preferred method consists of transferring a
      temporoparietal fascia flap to a subcutaneous pocket in the ipsilateral
      supraclavicular fossa and simultaneously placing a skin expander under both the
      fascia flap and the supraclavicular skin. After adequate expansion, the fascia
      becomes incorporated within the capsule of the expander, and the composite
      capsulofasciocutaneous flap can be safely transferred to the facial defect as the
      PIE flap. These patients show that supraclavicular PIE flaps can provide ample
      amounts of vascularized cutaneous tissue for the reconstruction of major facial
      defects. The necessary tissue is generated by expanding the most desirable tissue
      type available, and a selected vascular pedicle is induced to perfuse and carry
      that generated tissue. Compared with conventional expansion and adjacent flap
      transfers, PIE flaps allow the transfer of expanded skin to distant sites as
      island or free flaps perfused by the induced vascular pedicles.

PMID- 7732110
TI  - The free flap and plate in oromandibular reconstruction: long-term review and
      indications.
AB  - The purpose of this study was to define the role of reconstruction plates as bone
      replacement in oromandibular reconstruction. From 1987 through 1991, 71
      consecutive oral cancer patients underwent composite resection and reconstruction
      and were entered into one of two studies. In the first study of 31 patients, 15
      underwent oromandibular reconstruction using a radial forearm osteocutaneous
      flap, while the remainder (16) received a radial forearm fasciocutaneous flap
      together with a mandibular reconstruction plate. The second study involved 40
      subsequent patients, all receiving the latter form of reconstruction. Twenty-one
      of the plates were stainless steel, and the remaining 19 were of the titanium
      hollow screw (THORP) type. We followed the patients prospectively. We defined
      success as a reconstruction that we did not have to remove. Additionally, since
      the patients had limited life expectancy, we developed the idea of days of life
      lost and incorporated it into our definition of a successful outcome.
      Vascularized autogenous bone proved to be more successful than metallic plates
      used alone in terms both of reconstruction survival and of minimizing days of
      life lost. The overall success rate of mandibular plate reconstruction was 78.9
      percent, but analysis by defect type revealed a failure rate of 35 percent when
      the defects were anterior and only 5 percent when they were lateral. THORP plates
      demonstrated a trend towards more durability. We would now recommend plate
      reconstruction only in lateral defects in patients with a poor prognosis.

PMID- 7732111
TI  - Reduction mammaplasty: criteria for insurance coverage.
AB  - The guidelines by which insurers determine eligibility for coverage of reduction
      mammaplasty must rely largely on only subjective materials, yet they often apply
      strict criteria ranging from minimum resection weights to outright refusal to
      compensate. I have reviewed the data from 100 consecutive reduction mammaplasties
      performed by me over the last 2 years. Body weight, combined specimen weight, and
      height relationships were studied. Patient-identifiable questionnaires regarding
      the presence or absence of preoperative regional discomforts were sent to the
      same group. It was not possible to construct a useful formula that would verify
      either subject complaints of discomfort or the prospect for their relief based on
      body dimension or specimen weight. This study suggests that a graded, three-level
      minimum specimen weight standard for body weights less than 70 kg, 70 to 79 kg,
      and over 80 kg would be more equitable.

PMID- 7732112
TI  - Tissue humoral response to intact and ruptured silicone gel-filled prostheses.
AB  - Biopsies of the fibrous capsule in 31 women undergoing explanation of gel-filled
      breast prostheses and in 3 women with silicone gel-associated granulomas were
      tested for the presence of IgG, IgM, IgA, C3 complement, and fibrin using
      fluorescent antisera. Of a total of 41 prostheses removed, 9 were found to be
      ruptured but contained within the fibrous capsule or immediately adjacent to it.
      In the 3 women undergoing granuloma excision only, the sites were the arm (2) and
      the chest/axilla (1). In one patient, IgG, C3, and fibrin were detected in the
      capsule of an intact prosthesis. C3 and fibrin were present in the capsule
      surrounding one ruptured prosthesis. Fibrin was detected in the capsule of one
      other patient. Bilateral capsules surrounding intact prostheses removed from 4
      patients with collage-vascular diseases were negative for C3, fibrin, and
      immunoglobulins, as were the 3 granulomas from distant sites. Hematoxylin and
      eosin stains revealed a typical foreign-body response to gel in almost all cases.
      Both T- and B-cell lymphocytes are present in the infiltrate surrounding silicone
      gel. In this study, chronic exposure to silicone gel-filled prostheses did not
      result in antibody deposition or complement activation in the fibrous capsule or
      in the tissue surrounding gel droplets.

PMID- 7732113
TI  - Immediate autogenous breast reconstruction in clinically advanced disease.
AB  - Breast reconstruction is pursued more aggressively today. We have offered primary
      autogenous reconstruction to patients with advanced disease and review herein our
      experience with these patients to define the benefits or problems of this
      practice. We carried out immediate autologous tissue breast reconstruction in 21
      patients with disease in clinical stage IIb or higher, including 12 in stage III
      and 3 in stage IV. No patient experienced delay in the delivery of adjuvant
      chemotherapeutic or radiation treatment, and the reconstructed breasts tolerated
      these treatments well. Although 4 patients required biopsy of postoperative
      masses deep within the reconstructed breast, none proved to represent recurrence
      of disease. One patient developed cutaneous recurrence in a scar uniting
      mastectomy flap with reconstructive flap, and 2 had axillary recurrences. All
      were quickly detected and treated. Two patients with stage III disease and 2 with
      stage IV disease died from metastases, but with good local-regional control.
      Primary autogenous breast reconstruction may be offered to motivated patients
      regardless of disease stage.

PMID- 7732114
TI  - Management considerations for the granuloma of pregnancy.
AB  - The epulis gravidarum, or granuloma of pregnancy, represents a vascular lesion
      observed during gravidism. While histologic features may mimic those of generic
      pyogenic granulomas, the management may differ. Remarkably, the plastic surgical
      literature is conspicuously void of information concerning this common entity,
      with approximately 40 new cases being diagnosed and treated annually at our
      institution. With a review of the literature, we offer four typical and
      representative case reports that serve to highlight the pertinent physiology and
      treatment options. Guidelines are proposed to assist in the management of this
      disease process.

PMID- 7732115
TI  - Superficial x-ray therapy in keloid management: a retrospective study of 24 cases
      and literature review.
AB  - Radiotherapy for the management of keloids was introduced in 1906. Eighty-eight
      years later there is no consensus among physicians who treat keloids that
      radiotherapy is safe, although it is generally accepted that radiotherapy is
      effective in reducing the recurrence of keloids following excision. This paper
      reports on a retrospective study of 24 patients whose keloid postexcisional sites
      were treated with superficial x-ray therapy. This paper compares the author's
      results with the results of 18 studies reported by other investigators. The
      objective of the paper was to determine the effectiveness and safety of
      superficial x-ray therapy. The paper concludes that superficial x-ray therapy
      does reduce the rate of postexcisional keloid recurrence. It stresses the need
      for better controls in reporting on superficial x-ray therapy in keloid
      management. A multi-institutional prospective study is proposed, and a suggested
      protocol is outlined. There has been only one case report of a carcinoma
      occurring subsequent to the treatment of a keloid postexcisional site with
      radiotherapy, and the causal relation was questionable. A system for long-term
      follow-up of patients who receive superficial x-ray therapy is proposed.

PMID- 7732116
TI  - Fascial flap coverage of Achilles tendon defects.
AB  - The exposed, often desiccated Achilles tendon presents a difficult wound that
      cannot always be solved with the use of regional tissue. A series of 15
      consecutive patients with wounds associated with previous failed repairs (n = 5),
      radiation (n = 1), trauma (n = 4), pressure sores (n = 3), and burn contractures
      (n = 2) is presented. Patients with osteomyelitis of the calcaneus were not
      included. All were covered with free fascial flaps from parietotemporal or
      forearm donor sites and skin grafts. There were two partial flap losses.
      Complications were minimal, and all patients were mobilized and ambulating within
      2 months. Average follow-up was 4 years. Those with peripheral vascular
      insufficiency were revascularized prior to free tissue transfer. Vascularized
      fascia covered with skin grafts provides the treatment of choice for the
      localized Achilles tendon exposure not exceeding 10.0 cm. Advantages include (1)
      provision of thin, pliable tissue that permits gliding, (2) minimal bulk, (3)
      simultaneous donor- and recipient-site dissections, (4) transfer of mobile tissue
      that can be wrapped around tendon, and (5) early wound coverage and mobilization.

PMID- 7732117
TI  - Preliminary arteriovenous fistula for free-flap reconstruction in the diabetic
      foot.
AB  - We present our experience at the American University of Beirut Medical Center
      with two diabetic patients suffering from large necrotic and infected foot
      ulcers. Both patients were ambulatory at the time of presentation despite their
      extensive wounds and were believed to have a useful limb with adequate protective
      sensation worth saving. Below-knee amputation was prevented in both cases by
      successful soft-tissue coverage of the ulcers using microvascular composite
      tissue transfer a few days after performing a preliminary arteriovenous fistula
      with a long vein graft loop. The flap vessels were anastomosed end-to-end to the
      arterial and venous limbs of the divided arteriovenous loop. This reconstructive
      technique of difficult diabetic wounds of the lower extremity, though in two
      stages, may be safer than one long procedure in a high-risk patient. It is
      technically easier than long interpositional vein grafts at the same time as free
      flap transfer or microvascular anastomoses with small and diseased vessels. It
      definitely provides more chance of success as larger vessels are used to supply
      the flap. It permits distension of the vein graft at normotensive physiologic
      pressures and allows testing the arterial anastomosis as well as the venous flow
      before final flap transfer. Above all, it allows extreme freedom in performing
      tension-free anastomoses away from the infected wound.

PMID- 7732118
TI  - Analysis of 136 cases of reconstructed penis using various methods.
AB  - Our experience in reconstructive surgery of the penis in 136 cases is reported.
      The postoperative complication rate was 13.24 percent. Five methods were used:
      the radial forearm free flap, the superficial inferior epigastric artery flap,
      the superficial circumflex iliac artery flap, the anterolateral thigh flap, and
      the combined cutaneous flap. The choice of the method had to be made depending on
      the patient's condition and prediction of the operative results. The penis not
      only should have a good appearance with normal size but also should have good
      sensation and function. The keys to success of this operation are considered to
      be correct preoperative planning, careful manipulation, and excellent
      anastomoses.

PMID- 7732119
TI  - The use of demineralized bone powder in an onlay graft model.
AB  - Demineralized bone powder has been shown previously to successfully induce bone
      formation. The purpose of this study was to use demineralized bone powder in an
      onlay graft situation using implantable molds. Demineralized bone powder was
      placed within a mold and rigidly attached to the frontal bones of 30 New Zealand
      White rabbits by screw fixation. Periosteum was not closed over the mold. A
      control group had the mold placed without demineralized bone powder used. After
      12 weeks of growth, the animals were sacrificed and the frontal bone was analyzed
      for bone growth using standardized histology and fluorescent microscopy. One
      hundred percent of the animals (30 of 30) that received demineralized bone powder
      underwent bone growth in the precise shape of the mold (p < 0.001). There was no
      new bone development in the control group (n = 8). Placement of larger molds
      duplicated these results (n = 20) with a 650 percent increase in frontal bone
      thickness within 12 weeks after placement of demineralized bone powder. This
      model mimics onlay bone grafting, and perhaps this technique may replace onlay
      grafting or alloplastic implantation in certain circumstances, avoiding the extra
      morbidity and donor-site defects associated with bone grafting.

PMID- 7732120
TI  - The treatment of "malignant" exorbitism with an extended supraorbital
      advancement.

PMID- 7732121
TI  - Graft of breast tissue for correction of congenital asymmetry.
AB  - This represents a case of a graft of autogenous breast gland from the enlarged
      side to augment the hypoplastic breast in cases of congenital asymmetry. Long
      term consequences of this transfer and the thickness of the transferred gland
      that could be used remain unknown. It was with the patient's wishes and agreement
      to close follow-up that we undertook this approach to see if we could find a one
      step procedure for correction of asymmetry without the use of either foreign
      material or flap. Mammogram at 2 years is normal.

PMID- 7732122
TI  - Complete nasal agenesis with bilateral microphthalmia and unilateral duplication
      of the thumb.
AB  - Complete nasal aplasia is an extremely rare clinical entity and most infants are
      stillborn when this is associated with holoprosencephaly. A viable 3-year-old
      infant born with frontonasal arrest without holoprosencephaly is presented. The
      child's main complaint was lack of a nasal airway, which made eating extremely
      difficult. A method for craniofacial reconstruction of the nasopharynx is
      presented.

PMID- 7732123
TI  - Closure of palatal fistulas using a dermis-fat graft.

PMID- 7732124
TI  - Lip augmentation using the palmaris longus tendon.
AB  - A case is presented in which the upper lip of a 20-year-old woman was augmented
      by a graft of palmaris longus tendon-muscle. This technique offers several
      advantages over other lip enlargement techniques. The primary drawback, in my
      opinion, is the possibility that lip excursion (smiling, animation) might be
      restricted by tendon-muscle adherence to lip tissues, although this did not occur
      in this patient. Experience with larger numbers of patients is necessary before
      this technique can be endorsed for general use.

PMID- 7732125
TI  - A method for correction of congenitally inverted nipple with preservation of the
      ducts.
AB  - A method for correction of congenitally inverted nipple is described. It uses
      both the concept of creating a tight neck at the base of the inverted nipple and
      adding bulk to it. This is done without sacrificing the duct system in an attempt
      to allow patients to nurse normally.

PMID- 7732126
TI  - Reconstruction of the umbilicus: a simple technique.
AB  - The author proposes a simple technique for umbilical reconstruction. The new
      umbilicus is represented by an island flap that is sunken and then sutured to a
      circular skin defect drawn at the intersection of the xiphoid-pubic line and the
      transverse umbilical line. Before sinking, an accurate excision of the
      subcutaneous fat of the skin island is performed. A natural-looking elliptical
      scar is obtained, without any additional scar and providing good aesthetic
      results. The technique proposed can provide a good alternative to existing
      umbilicus reconstruction techniques.

PMID- 7732127
TI  - The influence of the St. Louis quadrumvirate on plastic surgery.

PMID- 7732128
TI  - Fibrous hamartomas of the scalp in infancy.

PMID- 7732129
TI  - Anomalous intracranial venous drainage: implications for cranial exposure in the
      craniofacial patient.

PMID- 7732130
TI  - Reversed cephalic vein in head and neck procedures utilizing free flaps.

PMID- 7732131
TI  - Reconstruction of composite mandibular defects.

PMID- 7732132
TI  - Fixation of silicone implants.

PMID- 7732133
TI  - Submental lipectomy with skin excision.

PMID- 7732134
TI  - Health risks of failed silicone gel breast implants.

PMID- 7732135
TI  - A positioning system for reconstructive and aesthetic breast surgery.

PMID- 7732136
TI  - Autotransfusion and reduction mammaplasty.

PMID- 7732137
TI  - Anatomic basis of local muscle flaps in the distal third of the leg.

PMID- 7732138
TI  - History of the American Society of Plastic and Reconstructive Surgeons.

PMID- 7732139
TI  - Possible anatomic grounds for TRAM failure.

PMID- 7732140
TI  - Resurfacing of both lips by nasolabial flaps.

PMID- 7732141
TI  - Tangential excision with a skin-grafting knife as an alternative for
      dermabrasion.

PMID- 7732142
TI  - Cervicofacial lymphatic malformation: clinical course, surgical intervention, and
      pathogenesis of skeletal hypertrophy.
AB  - This is a retrospective review of the clinical course and long-term soft
      tissue/skeletal problems in 17 patients with large cervicofacial lymphatic
      malformations. Morbidity included infection (71 percent), airway compromise
      requiring tracheostomy (65 percent), poor dental health with aggressive caries
      (53 percent), abnormal articulatory patterns (47 percent), and episodic bleeding
      (35 percent). All patients underwent soft-tissue excision (mean four procedures
      per patient). Damage to facial nerve (76 percent) and hypoglossal nerve (24
      percent) were common postoperative sequelae. Contour resection did not alter the
      progression of skeletal hypertrophy. Overgrowth most commonly occurred in the
      mandibular body, manifesting as anterior open bite deformity and class III
      occlusion (65 percent). Early mandibular body ostectomy was done in four children
      with grotesque hypertrophy. Jaw osteotomy was required in 71 percent of the
      patients to improve the maxillary/mandibular relationship. Histologic examination
      revealed intraosseous lymphatic malformation in areas of skeletal overgrowth in
      two-thirds of surgical specimens. The complexity of managing cervicofacial
      lymphatic malformation underscores the need for an interdisciplinary program in
      every major referral center.

PMID- 7732143
TI  - Residual problems in chest donor sites after microtia reconstruction: a long-term
      study.
AB  - The rib cartilage has been the most popular autogenous tissue for microtia
      reconstruction. In this study, 88 chest donor sites were evaluated in 80 patients
      examined in the outpatient clinic at least 1 year after tissue removal. Microtia
      reconstruction usually was initiated between the ages of 2 and 3 years (42
      percent), at which time an axial half of the sixth rib was harvested along with
      all of the seventh and eighth rib cartilages with their attached perichondrium.
      During this procedure, there were 19 uneventful pleural perforations (22
      percent), and early in the series, 2 patients (2 percent) required a chest tube.
      Postoperative atelectasis without evidence of pneumothorax occurred in 7 patients
      (8 percent). Chest scars were classified by impartial observers as excellent (25
      percent), good (33 percent), acceptable (28 percent), and poor (14 percent).
      Better scars were experienced in the cold-knife group than in incision by
      electrocutting. The younger group and the longer postoperative interval group
      showed better chest scars. Chest topography deformities were rated as normal (75
      percent), mild retrusion (19 percent), and severe retrusion (6 percent). Costal
      margin contours improved as the postoperative interval lengthened.

PMID- 7732144
TI  - Comparison of the Furlow double-opposing Z-palatoplasty with the Wardill-Kilner
      procedure for isolated clefts of the soft palate.
AB  - This retrospective investigation compared the operative experience speech results
      of 21 patients who underwent a Furlow double-opposing Z-palatoplasty with those
      of 10 patients who underwent a modified Wardill-Kilner procedure. The
      modification consisted of not incising the nasal mucosa. All patients presented
      with an isolated cleft of the soft palate and were operated on by a single
      surgeon. The choice of operative technique was based solely on the fact that the
      surgeon developed an increasing preference for the Furlow procedure over time.
      The mean age at surgery was 1.3 and 1.5 years for the Furlow group and the
      Wardill-Kilner group, respectively. The average postoperative follow-up was 2.5
      and 3.1 years, respectively. The mean operative times and hospital stay were the
      same for both groups. Postoperative speech assessments involved equal-appearing
      interval scale ratings of hypernasality and nasal emission, as well as pressure
      flow testing and perceptual judgments of overall velopharyngeal adequacy.
      Analysis failed to reveal any statistically or clinically significant differences
      between the two groups.

PMID- 7732145
TI  - Potential dangers of oxygen supplementation during facial surgery.
AB  - The use of local anesthesia and intravenous sedation has made same-day outpatient
      surgery a viable option for many aesthetic and reconstructive procedures. These
      procedures often include the use of supplemental oxygen. Oxygen-enriched
      environments increase the combustibility of most materials, and "oxygen pooling"
      has been suspected to play an integral role in intraoperative fires. A personal
      experience with an intraoperative explosion and fire during a cosmetic
      blepharoplasty compelled us to explore the potential danger inherent in the use
      of supplemental oxygen as well as potential strategies to minimize that danger.
      This study systematically examines the microenvironment created by the use of
      oxygen both in the operative field and beneath the surgical drapes under
      conditions simulating routine facial surgery and various recommended
      modifications of its delivery. With the use of oxygen supplementation, oxygen
      concentration beneath the drapes was found to be consistently elevated when
      compared with ambient air (20.9 percent) and reached levels as high as 53.5
      percent. Oxygen concentration in the operative environment was mildly but not
      significantly elevated. Although criteria for the use of oxygen supplementation
      are not clear, when administration is deemed necessary, the use of a posterior
      pharyngeal catheter for its delivery had no advantage over nasal prongs. However,
      appropriate alternatives include the use of "open face" draping techniques, the
      use of compressed air beneath the drapes as a substitute for oxygen
      supplementation in unsedated patients, and cessation of oxygen supplementation
      for 60 seconds prior to the use of a possible ignition source with oxygen flow
      rates of less than 3 liters per minute.

PMID- 7732146
TI  - Chin augmentation using minimally invasive technique and bioplastique.
AB  - The plethora of problematic techniques for improving minor chin recessions has
      left the plastic surgeon inevitably uncertain of the most effective remedy.
      Research we began in 1968 has led us to the development of a new biphasic polymer
      and minimally invasive implantation techniques aimed at solving the soft-tissue
      deficiency dilemma. Bioplastique consists of inert, textured particles of
      critical dimension dispersed within a bioexcretable gel vehicle. Previous
      experimentation in rabbit ears has shown that the gel component is rapidly
      phagocytosed, excreted, and replaced by a fibrin matrix within 3 days. The matrix
      is then replaced by host collagen, gradually forming a stable encasement around
      each microparticle. Further evaluation has revealed that the implant resists
      migration and absorption. Based on these encouraging results, a clinical phase
      was initiated. Thirteen patients lacking chin prominence have subsequently been
      improved with Bioplastique implants. The infection rate was 0 percent, and other
      complications were minor. At 26 months, no evidence of migration or absorption
      has been observed, and the aesthetic results remain.

PMID- 7732147
TI  - The anchor subperiosteal forehead lift.
AB  - The coronal incision used for brow lift procedure has a high rate of localized
      alopecia, widening, and depression of the scar at the suture line. Other sequelae
      of the standard coronal brow lift incision procedure are "stretch-back" with a
      recurrent brow ptosis, poor brow elevation, and numbness beyond the incision
      line. Factors causing alopecia are tension, use of a monopolar cautery, use of
      key sutures with undue tension, one-layer closure, and sutures left too long.
      Recurrent brow ptosis may be due to anterior displacement of the posterior scalp
      flap, stretching of the anterior frontal skin flap, or insufficient power of the
      weakened frontalis muscle. Poor brow elevation may be due to unsatisfactory
      dissection on the glabella and orbital rims. Numbness and itching beyond the
      incision line are due to a low coronal incision. To avoid these problems, the
      following principles were followed: (1) If not contraindicated, the incision is
      made high on the vertex of the head, posterior to a biauricular line. (2) The
      pericranium is included in the frontal flap starting at the incision lines. (3)
      The subperiosteal dissection is continued down to the orbital rims and nasal
      bones. (4) The release of the periosteum at the arcus marginalis or just above
      allows repositioning of the brow structures. (5) The inelastic pericranium
      maintains the position of the elevated structures and avoids stretching of the
      frontal skin. (6) The integrity of the frontalis muscle is maintained completely.
      (7) Two large triangles of scalp resected in the posterior flaps allow fixing the
      position of the posterior scalp and match better the length of the anterior flap.
      (8) The galea periosteal rim flap allows anchoring of the frontal flap to the
      undersurface of the posterior scalp flap. This stabilizes the closure with
      minimal tension on the hair-bearing portion of the scalp. The wide surface of
      contact avoids depression and widening at the suture line. (9) Closure with skin
      staples avoids constriction of the hair follicles. (10) Hemostasis is done with a
      bipolar cautery. (11) No through-and-through key sutures are used. Some of these
      principles were introduced to the endoscopic subperiosteal forehead lift. The
      modifications mentioned above have been used in 92 open brow/face lift procedures
      with excellent aesthetic and functional results and minimal complications.

PMID- 7732148
TI  - [The dialectic of the obsessionality and the dissociativity: toward a
      psychopathology of binge-eating].
AB  - Binge-eating is one of the most paradoxical phenomena in the symptomatology of
      anorexia nervosa and bulimia nervosa. The patients seem to be struggling to
      control their eating behaviors as strictly as possible, and at the same time,
      they repeat chaotic patterns of binge-eating. The author investigated the
      descriptive psychopathology of binge-eating in this paper. The author recognized
      the impulsive nature of binge-eating at first, and compared it with the clinical
      features of so-called impulse control disorders, such as kleptomania,
      trichotillomania, and so on. According to the literature review, most impulse
      control disorders tended to show high coincidence with eating disorders. The mode
      of the coincidence and the alternation of the symptoms suggested the common
      psychopathologies between eating disorders and impulse control disorders. The
      author then inquired into their common psychopathologies, and revealed
      characteristic features which could be formulated as dissociative. The study of
      the concept of dissociation proved that this formulation was not only valid, but
      also useful in understanding eating disorders clinically and theoretically. Binge
      eating could be regarded as a manifestation of dissociative pathology. The author
      inquired further into the psychopathologies of eating disorders and impulse
      control disorders, and revealed obsessional features in these disorders. Though
      some investigators regarded the symptoms of eating disorders as compulsive
      behaviors and considered that eating disorders were variants of obsessive
      compulsive disorder, the author pointed out some descriptive differences between
      them. Nevertheless, the obsessionality formed an important basis of the
      psychopathology of binge-eating. Finally, the author discussed the relationship
      between the obsessionality and the dissociativity in eating disorders. These two
      features were reciprocal factors in mental activity, and were forming dialectical
      dynamism in general psychological functioning. In anorexia nervosa and bulimia
      nervosa, the opposition between two factors was morbidly rigid and their
      sublation could not occur. Though the obsessional and the dissociative features
      of binge-eating were opposite phenomena, it was important to comprehend them as
      an incorporated psychopathology. The conceptualization of the dialectic of the
      obsessionality and the dissociativity could also be useful in understanding other
      psychopathological phenomena such as addiction and splitting.

PMID- 7732149
TI  - [A theory explaining the relation between "egorrhea symptoms" and "symptoms of
      being influenced" more efficiently than the existing theories--from the viewpoint
      of "experiencial type" as opposed to symptomatological direction].
AB  - Fujinawa, A. and his co-researchers have categorized symptoms of ego disorder
      into two opposing symptoms; "egorrhea symptoms" having the direction of "Inside
      to Outside" in their symptomatological structure and "symptoms of being
      influenced" having the direction of "Outside to Inside". They have also proposed,
      for ideal cases, the following: (1) "Egorrhea symptoms" are schizophrenic ego
      disorders. (2) These two types of symptoms are independent and opposing series of
      ego disorder. (3) There exists a new entity named "egorrhea type of
      schizophrenia" which is mainly characterized by "egorrhea symptoms" and opposed
      to the common type of schizophrenia which is mainly characterized by "symptoms of
      being influenced". The author, however, indicated several faults in their
      propositions and revised them from their same viewpoint. The author then
      proposed, from the viewpint of intentionality, the following: (1) Any symptom
      exhibits one of two opposite direction of intentionality; one exhibits
      intentionality to an object ("object experiencial type") and the other exhibits
      intentionality to the subject itself ("subject experiencial type"). (2) Symptoms
      of each "experiencial type" are related to each other and therefore make the
      state be composed mainly of them. The author attempted to compare his theory with
      Fujinawa. A. and his co-researchers theory and the revised one. 58 hallucinatory
      delusional cases (29 schizophrenic cases, 29 non-schizophrenic cases) were
      examined. Some results were as follows: (1) "Egorrhea symptoms" are not peculiar
      to schizophrenia. (2) A special type of auditory hallucination, which occurs when
      the patient sees others, is statistically related to "egorrhea symptoms". (3) The
      other common type of auditory hallucination, which occurs when the patient cannot
      see others, is statistically related to "symptoms of being influenced". The
      theory proposed by the author explains these results satisfactorily compared with
      the former two theories. That is, (1) is not against the theory, and (2) is
      considered to be caused by the relation between the special type of auditory
      hallucination and "egorrhea symptoms" having the same object experiencial type of
      symptoms, and (3) is considered to be caused by the relation between the common
      type of auditory hallucination and "symptom of being influenced" having the same
      subject experiencial type of symptoms. The author further deduced the
      developmental series of symptoms and states from his theory and examined them
      with the data from the above 58 cases and other cases reported by other
      researchers. As a result, much of the data was successfully explained by his
      theory.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7732150
TI  - [An attempt to prevent psychological distress induced by magnetic resonance
      imaging: effectiveness of psychological interventions].
AB  - A magnetic resonance imaging (MRI) examination has reportedly produced
      psychological distress such as discomfort, anxiety and fear in a certain number
      of patients. In an attempt to prevent such distress during an MRI, the authors
      took the following psychological measures: 1) improved psychological support for
      patients by MRI technicians; 2) providing sufficient information to patients
      about the imager and the nature of the examination; 3) reassurance of the safety,
      with the patient free to terminate the examination at any time; 4) environmental
      modification to induce relaxation, including recorded music, paintings and live
      plants in the examination room. We then evaluated the effectiveness of these
      combined psychological support factors for all MRI patients. A questionnaire on
      psychological distress experienced during an MRI was filled out by 143 patients
      (mean age, 49.4 years) and 105 patients (mean age, 48.4 years) prior to and after
      our psychological measures, respectively, after MRI test in Saiseikai Nakatsu
      hospital, and comparisons made between these two groups (chi 2 test, p < 0.05).
      The number of patients experiencing psychological distress during an MRI was
      significantly decreased (50.5%) after the measures were implemented as compared
      to the number (64.3%) beforehand. In particular, female, 60 or older patients and
      patients examined for the first time showed significant decreases in experiencing
      psychological distress after the measures were implemented. The number of
      patients who reported distress, tended to decrease. Patients who developed
      certain symptoms, such as palpitation, also tended to decrease. Patients who
      reported the "long examination time" as a distress factor and those who developed
      palpitation during the examination significantly decreased. Our results indicate
      that these combined psychological measures are efficacious in reducing
      psychological distress during an MRI, mainly by curtailing the patient's
      subjective sense of examination time. In addition to an MRI examination, our
      psychological measures should be applied to other medical examinations which tend
      to generate undue psychological distress.

PMID- 7732151
TI  - [A case of schizophrenia with "uninformed" medication of antipsychotic drug in
      community--remodeling the concept of "protection" in informed consent].

PMID- 7732152
TI  - [An experimental study for the physical examination system in psychic in
      patients].

PMID- 7732153
TI  - [Outcome of schizophrenia--extended observation (more than 30 years) of 129
      typical schizophrenic cases [III]].
AB  - We had already made a report on outcome of schizophrenia (1986). The patients,
      129 typical schizophrenia, were continuously observed over 30 years in the
      Kawagoe Dojinkai Hospital. Recently, we again evaluated their prognoses according
      to the same criteria as adopted in the first report, and divided them into the
      following five groups. [symbol: see text]: completely remitted group (21 persons,
      16.3%), [symbol: see text]: almost remitted cases now holding jobs (23 persons,
      17.8%), [symbol: see text]: Slightly remitted group showing good adjustment at
      home or hospital (41 persons, 31.8%), [symbol: see text]: maladjusted cases
      always showing an unfavorable condition (25 persons, 19.4%), x : incurable cases
      (19 persons, 14.7%). 1) In the last 8 years, there were 30 persons (23.3% of the
      whole patients) who showed prognostic changes (10 persons improved, 20 persons
      worsen). While the second group ([symbol: see text]) has seen fewer persons (12
      persons down) than previous study, the third group ([symbol: see text]) has seen
      more persons (9 persons up). Each three groups, that is, the first two groups
      ([symbol: see text] + [symbol: see text], 44 persons, 34.1%), the third group
      ([symbol: see text], 41 persons, 31.8%), and the forth and fifth groups ([symbol:
      see text] + x, 44 persons, 34.1%) accounted for a third of the whole patients. It
      is after 32 years on the average (extending from 21 to 50 years) from the onset
      of illness that they showed prognostic changes. 2) Generally speaking, catatonic
      patients had favorable prognoses, hebephrenic patients unfavorable ones, and
      paranoid patients medium ones. But 4 improved persons in the forth and fifth
      groups were all hebephrenic type. 3) 17 among the 30 persons who showed
      prognostic changes were unstable type. They took a wave-like course. 4) 27 of all
      the 129 patients were dead. 25 were dead from disease mentioned below. Malignancy
      (8 persons), Cerebral vascular disease, Pneumonia and Diabetes (3 persons), Heart
      failure (2 persons), Ileus, Myocardial infarction, Hepato-cirrhosis, Gastric
      ulcer, Tuberculosis and Natural death (1 person). 2 persons committed suicide. 5)
      Outcome of 45 patients who discontinued our medical therapy became clear as
      follows. [symbol: see text] + [symbol: see text]: 18 persons (40.0%), [symbol:
      see text]: 9 persons (20.0%), [symbol: see text] + x : 18 persons (40.0%). A
      smaller percentage of the patients belongs to the third group ([symbol: see
      text]) than that of our patients who were continuously followed by us.

PMID- 7732154
TI  - Social support as a moderator of cardiovascular reactivity in women: a test of
      the direct effects and buffering hypotheses.
AB  - This study examines the possibility that social support operates as a moderator
      of cardiovascular reactivity in women. Two models by which social support may
      operate were examined: the direct effects and buffering models. Twenty-six
      subjects were exposed to four conditions while playing a video game: two levels
      of stress (low, high) and two levels of social support (alone, together). Blood
      pressure and heart rate were monitored continuously. Ratings of stress were
      obtained for each condition. Results indicated that the support manipulation
      produced significant main effects for diastolic blood pressure and stress
      ratings, with lower diastolic blood pressure and ratings observed in the
      "together" condition, and that the interaction between support and stress
      produced lower reactivity for the cardiovascular measures in the high stress (but
      not the low stress) condition. No interaction was found for the stress ratings.
      We conclude that the results provide support for both the buffering and direct
      effects models. Implications concerning the (within-subjects) design of the study
      and the stress ratings are discussed.

PMID- 7732155
TI  - Sex-specific effects of social support on cortisol and subjective responses to
      acute psychological stress.
AB  - The effects of short-term social support on cortisol levels and subjective
      responses to acute psychological stress were investigated in healthy adults
      (total N = 66). In anticipation of a public-speaking task in front of an
      audience, subjects received either no social support ("no support") or social
      support from an opposite-sex stranger ("stranger") or from their boyfriend or
      girlfriend ("partner"). Support providers were instructed to enact both
      instrumental and emotional support during the 10-minute anticipation period. The
      results obtained suggest sex-specific effects of social support. Although men in
      the partner support condition showed significant attenuation of cortisol
      responses compared with unsupported and stranger-supported men, women showed no
      response decrement under stranger support. In contrast to men, women showed a
      tendency toward increased cortisol responses when supported by their boyfriends.
      The endocrine response differences between male and female subjects were
      unrelated to questionnaire-derived psychological variables. No sex and group
      differences in perceived stress, mood changes, or social desirability were
      observed. Although the overall level of subjective well-being throughout the
      experiment was elevated in the partner support condition, no sex or group
      differences were observed in perceived stress, well-being changes, and social
      desirability. Opposite to their cortisol responses, women rated both stranger and
      partner support attempts more favorably than did men. No significant correlations
      were observed between the perceived stressfulness of the situation, mood changes,
      and cortisol responses. These results provide preliminary evidence for sex
      specific patterns of social support efficacy to acute psychological stress with
      respect to adrenocortical responses.

PMID- 7732156
TI  - Social support and the development of immune function in human immunodeficiency
      virus infection.
AB  - A psychosocial investigation offered to all human immunodeficiency virus (HIV)
      infected men with moderately severe or severe hemophilia in Sweden was made in
      1986. Most of these men had been infected in the years 1980 to 1984 and told
      about their infections in 1985. Forty-nine subjects had answered questions in
      regard to sources of emotional support in their life situation. Based on the
      responses to these questions a score of "availability of attachment" (AVAT) was
      calculated, and two groups of patients were identified: one with high AVAT and
      one with low AVAT scores. The subjects were followed with regard to the state of
      their immune system, as reflected by CD4 counts, until 1990. The results
      indicated that a low AVAT score in 1985 was associated with a significantly more
      rapid progressive deterioration in CD4 count during subsequent years. The
      mechanism behind this association is unknown. Several possible confounders were
      not studied. However, if the association between a poor AVAT score and rapid CD4
      deterioration after HIV infection is replicated in other samples, it could be
      important to the future clinical care of HIV-infected subjects.

PMID- 7732157
TI  - Seeking medical care in response to symptoms and life stress.
AB  - Analyses tested the following contrasting hypotheses: a) The occurrence of a new
      symptom in the presence of ongoing life stress increases the attribution of
      symptoms to illness and increases the use of health care; b) new symptoms
      occurring in the presence of ongoing life stress are attributed to stressors if
      they are ambiguous indicators of illness, and they are unlikely to motivate care
      seeking if the stressor, i.e., the perceived cause, is of recent onset. The 43-to
      92-year old subjects in this longitudinal study were less likely to seek care for
      the ambiguous symptoms they experienced during the previous week if there was a
      concurrent life stressor that began during the previous 3 weeks; these symptoms
      were attributed to stress rather than to illness, and subjects tolerated the
      emotional distress caused by the combination of a stressor and an ambiguous
      symptom. Subjects were less willing to tolerate the combined distress of an
      ambiguous symptom and a concurrent life stressor if the stressor onset was not
      recent; under such conditions, subjects were more likely to seek health care.
      Current life stressors did not affect care-seeking for symptoms that were clear
      signs of disease; these symptoms were readily identified as health threats in
      need of medical attention. The findings contribute to a better theoretical
      understanding of how individuals perceive their physical states and how they cope
      with stress. Practical implications of these findings for increasing efficient
      use of health care services are also discussed.

PMID- 7732158
TI  - Health-care-seeking behavior: implications for the primary care physician.

PMID- 7732159
TI  - Lack of social participation or religious strength and comfort as risk factors
      for death after cardiac surgery in the elderly.
AB  - The purpose of this study was to examine the relationship of social support and
      religion to mortality after elective open heart surgery in older patients. Of the
      232 patients included in the study, 21 died within 6 months of surgery. Three
      biomedical variables were significant predictors of mortality and selected as
      adjustment variables for a multivariate analysis: history of previous cardiac
      surgery; greater impairment in presurgery basic activities of daily living; and
      older age. Among the social support and religion variables, two were consistent
      predictors of mortality in the multivariate analyses: lack of participation in
      social or community groups and absence of strength and comfort from religion.
      These results suggest that in older persons lack of participation in groups and
      absence of strength and comfort in religion are independently related to risk for
      death during the 6-month period after cardiac surgery.

PMID- 7732160
TI  - Do low cholesterol levels slow mental processing?
AB  - The plasma cholesterol levels of 279 students were measured and related to
      decision and movement times in choice reaction time tasks with one, two, four,
      and eight lamps. In female subjects, low plasma cholesterol levels were
      associated with slower movement times and, when responding to one or two lamps,
      slower decision times. In male subjects, there was a nonlinear relationship
      between cholesterol level and decision times. Because these data are
      correlational in nature, it is not possible to assume a causal relationship
      between cholesterol levels and speed of mental processing. The literature,
      however, supports the suggestion that further work should consider the
      possibility of a causal relationship.

PMID- 7732161
TI  - Hormones and the physiological architecture of life history evolution.
AB  - Hormones play key roles in the regulation of animal and plant life histories,
      particularly in the timing of transitions between prematurational stages and in
      the scheduling of reproduction. Furthermore, hormonal mechanisms are subject to
      information about the external and internal environment of the individual. Within
      an evolutionary radiation, the same hormone subsets often regulate the schedules
      of development as well as adult reproduction and related activities and,
      moreover, are involved in mechanisms of senescence. We propose that the
      pleiotropic and epistatic effects from hormonal and neural mechanisms are an
      important substratum for life history evolution. This analysis of hormonal
      mechanisms in senescence implicates a role for antagonistic pleiotropy in
      selection for particular subsets of hormonal mechanisms that can be traced
      throughout prematurational and postmaturational stages. In the example of the
      vertebrate MHC (major histocompatibility complex), polymorphic loci have been
      assembled with pleiotropic actions on several regulatory axes affecting
      reproduction and other fitness components. We argue that the MHC and other
      complex loci may be considered as life history gene complexes, with pleiotropic
      influences throughout the lifespan. While analyses of this kind might suggest
      that life histories could be evolutionarily rigid, in our interpretation the
      population genetics that is involved provides a theoretical basis for great
      flexibility in hormonal regulation during life history evolution. It is possible
      that life history evolution among taxonomic groups may sometimes be chaotic,
      which would frustrate strong inferences by the comparative method in the study of
      life histories between taxonomic groups.

PMID- 7732162
TI  - Refractory rheumatoid arthritis. Therapeutic options.
AB  - Because rheumatoid arthritis rarely remits, refractory disease is common.
      Attention should be paid to aggravating comorbid conditions. Pharmacologic
      options currently available include cyclosporin, high-dose methotrexate,
      combination second-line agents, and creative use of corticosteroids. The
      available literature is reviewed in this article and the potential risks and
      benefits of the various options are discussed.

PMID- 7732163
TI  - Management of refractory ankylosing spondylitis and related
      spondyloarthropathies.
AB  - Ankylosing spondylitis is the prototype of an interrelated group of disorders
      termed spondyloarthropathies, which include reactive arthritis, psoriatic
      arthritis, and rheumatic disorders associated with inflammatory bowel disease. It
      can be difficult to differentiate between these disorders because they may occur
      simultaneously or sequentially. In addition, some of the clinical characteristics
      of these diseases, such as enthesiopathy and eye involvement, are similar no
      matter what the diagnosis. The monitoring, diagnosis, and treatment of these
      diseases are related more to their clinical presentation than to the precise
      diagnosis.

PMID- 7732164
TI  - Treatment of refractory psoriatic arthritis.
AB  - Psoriatic arthritis occurs in approximately 5% of patients with psoriasis and can
      lead to significant morbidity. Treatment options for refractory psoriatic
      arthritis can be divided into (1) medications used in the treatment of other
      rheumatic diseases and (2) experimental agents. This article reviews available
      therapeutic agents for psoriatic arthritis and outlines an approach to treatment.
      The use of physiotherapy and surgery and the management of arthritis mutilans are
      also reviewed.

PMID- 7732165
TI  - Treatment of refractory crystal-associated arthritis.
AB  - Crystal-associated arthritis includes gout, calcium pyrophosphate deposition
      (CPPD) disease, and the basic calcium phosphate (BCP)-related syndromes. In this
      article, the authors discuss the use of drug combinations and steroids for
      refractory gout patients and recommend management strategies for gout in the
      organ transplant recipient. Difficult cases of CPPD disease can be treated with
      colchicine and intra-articular steroids. The BCP-associated syndromes are best
      managed with NSAIDs and intraarticular measures. Experimental therapies for all
      forms of crystal-related arthritis are also discussed.

PMID- 7732166
TI  - Refractory osteoarthritis. Differential diagnosis and therapy.
AB  - The patient with osteoarthritis and severe or resistant pain should be evaluated
      for coexistent mechanical problems or distinct diseases. Treatment remains
      symptomatic and empiric. The value of many frequently used invasive therapies
      remains unproven given the large placebo response rate in osteoarthritis. In this
      article, the many new agents in development that may prove to be
      chondroprotective are discussed.

PMID- 7732167
TI  - The treatment of myositis. How to approach resistant disease.
AB  - Idiopathic inflammatory myopathies, polymyositis, dermatomyositis, and inclusion
      body myositis, are increasingly recognized to cause long-term disability in
      certain subsets of patients. Because these diseases are infrequent, only
      retrospective analysis of most treatments are available. In this article,
      identification of subsets of patients with different prognoses and discussion of
      confounding factors for increasing weakness are emphasized. The advantages and
      disadvantages of different therapies for myositis and for extraskeletal muscle
      features are also discussed.

PMID- 7732168
TI  - Surgical and rehabilitation options in the treatment of the rheumatoid arthritis
      patient resistant to pharmacologic agents.
AB  - People with rheumatoid arthritis whose disease is poorly controlled with
      pharmacologic agents require treatment designed to reduce pain and inflammation
      and promote function and mechanical alignment. The proper evaluation of the
      musculoskeletal system and the patient's functional level must be performed.
      Heat, cold, splints, adaptive equipment, exercise, alternative therapies, and
      surgery are important adjunctive treatments for disease modulation and to
      maintain function and well being.

PMID- 7732169
TI  - Systemic sclerosis (scleroderma). Clinical management of its major complications.
AB  - Systemic sclerosis (scleroderma) is a disease of unknown cause whose pathogenesis
      involves interaction between the vasculature, the immune system, and connective
      tissue cells. Although specific therapy awaits a better understanding of its
      pathogenesis, proper management may enhance not only the duration, but the
      quality of life for most scleroderma patients. Presently, controlled prospective
      trials of therapeutic agents are lacking. Published reports of drug therapy for
      skin, kidney, cardiac, pulmonary, and gastrointestinal complications, as well as
      management of Raynaud's phenomenon, are critically reviewed in this article, and
      the authors' approach to management of difficult clinical problems is presented.

PMID- 7732170
TI  - Management of Lyme disease refractory to antibiotic therapy.
AB  - Lyme disease has become a major public health problem. One result of this anxiety
      is over-diagnosis and over-treatment in many endemic and near-to-endemic areas.
      The diagnosis of Lyme disease is often made solely on the basis of often
      misinterpreted serologic tests. Therefore, a major reason for inadequate response
      to antibiotic therapy is initial misdiagnosis. Persisting inflammation and tissue
      damage following treated Lyme disease does occur but is probably an uncommon
      cause of refractory symptoms and long-term debility post-Lyme disease.

PMID- 7732171
TI  - Eosinophilic rheumatic disorders.
AB  - Almost any rheumatic disorder can occasionally be characterized by the presence
      of eosinophilia, but there are only a few in which eosinophilia is a defining
      characteristic. These include eosinophilic fasciitis as well as toxin-induced
      disorders such as eosinophilia-myalgia syndrome and toxic oil syndrome. The
      epidemiology, clinical features, and pathogenesis of these conditions are
      reviewed in this article, and a rational approach to management of these entities
      is discussed.

PMID- 7732172
TI  - Treatment of "resistant" fibromyalgia.
AB  - Long-term outcome for the majority of patients with fibromyalgia is sufficiently
      disappointing so that most patients can be considered to have "resistant"
      disease. Among published treatments, education, active exercise, and nighttime
      antidepressant medications perform best. Patients eligible for treatment include
      those with primarily regional symptoms, wide-spread pain without 11 or fewer
      tender points, or "typical patients" as defined by the American College of
      Rheumatology criteria. Factors important in the process of prognosis of the
      syndrome should be identified and addressed in an integrated therapeutic program
      in order to positively influence outcome.

PMID- 7732173
TI  - Therapy of resistant systemic necrotizing vasculitis. Polyarteritis, Churg
      Strauss syndrome, Wegener's granulomatosis, and hypersensitivity vasculitis group
      disorders.
AB  - The systemic necrotizing vasculitides represent a difficult group of diseases
      from a therapeutic perspective. Even with successful therapy patients often
      experience a high degree of disease and treatment morbidity. Refractory disease,
      or that which fails to respond to standard therapy, is particularly challenging.
      A clinical approach to several vasculitic syndromes is outlined in this article
      with emphasis given to therapies supported by controlled investigations and those
      supported by consensus opinion where available.

PMID- 7732174
TI  - Treatment of corticosteroid-resistant giant cell arteritis.
AB  - The literature about the treatment of giant cell arteritis (GCA) is diverse and
      often includes patients with polymyalgia rheumatica (PMR) who do not have
      concurrent features of GCA. Consequent heterogeneity has contributed to
      controversy in the analysis of clinical data. Nevertheless, we have critically
      reviewed this literature to derive a rational approach to initial and maintenance
      corticosteroid (CS) therapy and thus define "CS-resistant GCA." In this article,
      the authors review what has been written about the treatment of presumed CS
      resistant disease. Although firm recommendations are lacking, the authors provide
      algorithms for the treatment of GCA patients who fail to respond to initial CS
      therapy or who require potentially toxic maintenance-dose CS therapy. A study
      design that may help to resolve the dilemmas that were found during our analysis
      is also outlined.

PMID- 7732175
TI  - Treatment of resistant Takayasu's arteritis.
AB  - About 20% of patients will have a monophasic, often self-limiting illness that
      does not require immunosuppressive therapy. Half of all patients that require
      corticosteroid therapy may achieve remission and discontinue medication without
      relapse. The other half of this group has glucocorticoid-resistant or relapsing
      disease, for which cytotoxic agents may induce remission or allow for disease
      control with lower doses of glucocorticoids. Although it is possible, it is
      desirable to distinguish those features of disease for which treatment is
      primarily best provided by immunosuppressive agents from those abnormalities that
      are due to critical vascular anatomic changes for which surgery or angioplasty
      are more appropriate.

PMID- 7732176
TI  - Severe major organ involvement in systemic lupus erythematosus. Diagnosis and
      management.
AB  - Deterioration in the function of major organs in patients with systemic lupus
      erythematosus may be due to causes directly related to the disease itself or to
      non-lupus related causes. In patients with rapidly progressive immune-mediated
      disease, therapy may be initiated with pulse glucocorticoids alone or in
      combination with pulse cyclophosphamide. For selected patients with aggressive
      life-threatening disease or patients refractory to treatment, experimental
      therapies such as plasmapheresis or intravenous immunoglobulin may be used as
      adjuncts in their management.

PMID- 7732177
TI  - Treatment of refractory cutaneous lupus erythematosus.
AB  - Photoprotection, topical steroids, and hydroxychloroquine are the mainstays of
      therapy of cutaneous LE. In severe and/or refractory disease, antimalarials
      remain the drugs of choice, and multiple induction and combination strategies can
      be employed to achieve optimal results with minimal toxicity. Retinoids, dapsone,
      clofazimine, and thalidomide are effective but more toxic alternatives. Their use
      dictates frequent and careful monitoring. Retinoids and thalidomide are
      teratogenic, and thalidomide is not available in the United States. Results with
      vitamin E are controversial. Gold and IFN-alpha have unacceptably high risk to
      benefit ratios. Cytotoxic agents are generally restricted to the patients with
      concomitant organ-threatening systemic disease.

PMID- 7732178
TI  - [Anisakiasis, an emerging parasitosis in our country].

PMID- 7732179
TI  - [Tubercular disease and its treatment].

PMID- 7732180
TI  - [Nodular asymmetric goitre with progressive growth and positive antithyroid
      antibodies].

PMID- 7732181
TI  - [Skin lesions in a patient with trochanteritis].

PMID- 7732182
TI  - [Diarrhea and fecal expulsion of whitish structure in a patient with acquired
      immunodeficiency syndrome].

PMID- 7732183
TI  - [Fever, generalized rigidity and stridor].

PMID- 7732184
TI  - [Large T-cell (Ki-1) anaplastic lymphoma in a patient with human immunodeficiency
      virus infection, an exceptional association].

PMID- 7732185
TI  - [Idiopathic T CD4+ lymphocytopenia and opportunistic infection without human
      immunodeficiency virus infection].

PMID- 7732186
TI  - [Infective endocarditis in drug addicts].

PMID- 7732187
TI  - [Adrenal insufficiency in amyloidosis secondary to rheumatoid arthritis].

PMID- 7732188
TI  - [Indications for continuous positive pressure ventilation].

PMID- 7732189
TI  - [Airway continuous positive pressure in acute respiratory failure caused by
      Pneumocystis carinii pneumonia].
AB  - OBJECTIVE: To evaluate the efficiency of continuous positive airway pressure
      through a face mask in acute respiratory insufficiency (ARI) secondary to
      Pneumocystis carinii pneumonia. DESIGN: Prospective study. SETTING:
      Multidisciplinary ICU. PATIENTS: Fifteen patients with ARI secondary to
      Pneumocystis carinii pneumonia were studied. INTERVENTIONS: Initially al patients
      received high flow oxygen therapy through a face mask for 60 minutes (Pre-CPAP
      phase); then CPAP through a face mask, with identical FiO2 and for a similar
      period of time (Pst-CPAP phase). At the end of each phase the following
      parameters were evaluated: respiratory rate, heart rate, arterial gases, acid
      base balance, and respiratory muscle motility. MEASUREMENTS: After oxygen therapy
      all fifteen patients had similar variables. After 60 minutes with CPAP through a
      face mask, significant improvements were noted for respiratory rate, heart rate,
      muscular effort, PaO2, SaO2, and PaO2/FiO2 (p < 0.001) in eleven patients, who
      survived after a mean stay of 8.5 days in the ICU with no evidence of major
      complications. In contrast, CPAP failed in four patients as respiratory rate,
      heart rate and vigorous muscle effort remained unchanged and, although PaO2 and
      SaO2 increased, the obtained values were significantly lower than in the
      remaining patients. Consequently, they underwent intubation and mechanical
      ventilation and after a mean stay of fourteen days with this ventilatory option
      died. CONCLUSIONS: These results confirm that CPAP through a face mask is an
      effective means to improve oxygenation in patients with Pneumocystis carinii
      pneumonia who develop hypoxemic respiratory insufficiency. Its early introduction
      in hospital protocols can help improving the prognosis in certain patients with
      severe PCP and avoid their admission to ICU, which would be thus preserved for
      those patients requiring mechanical ventilation.

PMID- 7732190
TI  - [Evaluation of serum adenosine deaminase as a prognostic marker in the treatment
      of human immunodeficiency virus infection with zidovudine].
AB  - BACKGROUND: Adenosine deaminase (ADA) is a key enzyme in cellular immunity. It
      catalyses the reaction 2'deoxyadenosine to 2'deoxiinosine, a critical step in the
      production of essential metabolites for the synthesis of nucleic acids. Its main
      physiological activity occurs in T cells of lymphoid tissue. The advanced HIV
      infection is characterized by a severe and progressive cellular immunity
      compromise. Partial positive results have been obtained with Zidovudine (AZT), a
      drug which Serum adenosine deaminase has been proposed as a useful marker for the
      assessment of the therapy response in these patients. METHODS: Serum ADA activity
      was determined in patients infected with HIV in stage II, before and after four
      months of therapy with AZT, regarding variations in its activity with
      improvements in biological parameters--CD4 and CD8 lymphocytes. RESULTS: Patients
      infected with HIV showed a significant increase in ADA activity compared with
      patients in the control group: 21.6 +/- 5.4 vs. 10.4 +/- 2.3 U/l (p < 0.001).
      Therapy with AZT decreased ADA activity: 21.6 +/- 5.4 vs. 15.2 +/- 4.3 U/l (p <
      0.001) and correlated with an increase in CD4 counts: 187 +/- 105 vs. 353 +/-
      145/mm3 (p < 0.001) and in CD4/CD8 ratio: 0.188 +/- 0.10 vs. 0.382 +/- 0.18 (p <
      0.001). CONCLUSIONS: The detection of a decrease in ADA correlates significantly
      with a favourable outcome in immunological parameters in individuals infected
      with HIV in stage II of disease treated with AZT.

PMID- 7732191
TI  - [Thrombocytopenia associated with human immunodeficiency virus infection.
      Pathogenic significance of platelet autoimmunity phenomena].
AB  - OBJECTIVES: Several mechanisms in formation and destruction of platelets could be
      involved in thrombocytopenia associated with HIV infection (TP/HIV). This
      epidemiological study investigated the pathogenic role of immunoglobulins
      associated with platelets (IAP), circulant immunocomplexes (CIC) and
      anticardiolipin antibodies (ACA) in patients with TP/HIV: PATIENTS AND METHODS: A
      total of 207 adults patients infected with HIV were studied. Patients were
      classified as thrombocytopenic (platelet count < 100,000/mm3, n = 68); borderline
      thrombocytopenic (platelet count from 100,000 to 150,000/mm3, n = 23) and non
      thrombopenic (platelet count > 150,000/m3, n = 116). IAP were investigated by an
      immunofluorescence technique with flow cytometry reading and eluate technique.
      CIC were investigated by C1q fixation measured by nephelometry. IgG-ACA
      determination was made with a commercially available ELISA technique. RESULTS:
      Prevalence of thrombocytopenia in the general cohort of seropositive patients was
      16%. Fifteen per cent of these patients had severe TP. There were no significant
      differences in epidemiology or prognosis among patients with and without TP.
      Patients with TP/HIV had increase rates of IAP, CIC and ACA (78%, 42% and 89%).
      These parameters were also increased in a similar percentage of non-TP infected
      patients (73%, 52%, 94% respectively). No correlation was observed between
      platelet counts and values of these immunological phenomena. CONCLUSIONS: TP/HIV
      is common, mild, with no prognostic significance and occurs in an heterogeneous
      patient population. Immune phenomena associated with a decreased platelet
      survival occur nonspecifically and with an uncertain pathogenic meaning.

PMID- 7732192
TI  - [Intensive chemotherapy with support of peripheral hematopoietic progenitor
      cells, mobilized with high-dose cyclophosphamide and G-CSF: fast hematologic
      recovery].
AB  - BACKGROUND: Hematopoietic progenitor cells mobilized to peripheral blood by a
      chemotherapy combined or not with hematopoietic growth factors and harvested with
      cyto-apheresis (CTA) provide a rapid hematological recovery when infused as a
      support step after intensive chemotherapy (IC). METHODS: Cyclophosphamide (CI) 4
      g/m2 and G-CSF 5 mcg/kg/d were administered to 19 patients with a solid tumor or
      lymphoma. Daily CTA were performed during hematological recovery to harvest > 2.5
      x 10(6) cells CD34+/kg. Seventeen patients received IC with infusion of
      peripheral hematopoietic progenitor cells (PHPC) and G-CSF. RESULTS: A total of
      52 CTA were performed, with a median (M) of 2 per patient. A M of 4.4 x 10(8)
      mononucleated cells/kg and 9.8 x 10(6) CD34+/kg were harvested per patient.
      Hematological recovery after IC with support of PHPC and G-CSF was rapid in all
      cases, but the aplastic period was shorter in the ten patients who received > 5 x
      10(6) CD34+/kg cells than in the seven patients with < 5 x 10(6) kg: The median
      of recovery to neutrophils > 0.5 x 10(9)/l was 8 days compared with 9 days (p =
      0.0005), to platelets > 20 x 10(9)/l of 8 days compared with 12 days (p = 0.001),
      and to platelets > 50 x 10(9)/l of 11 days compared with 14 days (p = 0.001).
      CONCLUSIONS: Toxicity of IC (4 g/m2) with G-CSF is moderate and allows the
      harvesting of an adequate number of PHPC. Its infusion after IC provides a rapid
      hematological recovery, which was more marked in patients receiving 5 x 10(6)
      CD34+/kg cells, than with the same IC schedules of IC with autologous bone marrow
      transplantation.

PMID- 7732193
TI  - [Liver tuberculous abscess in patients with human immunodeficiency virus
      infection: report of 2 cases and review of the literature].
AB  - Two cases are reported of hepatic tuberculous abscesses (HTBA) in patients
      infected with the human immunodeficiency virus (HIV), stressing the rarity of
      this location. Likewise, a review is made of cases reported in the literature.
      Our two patients presented with a prolonged febrile condition, with
      constitutional symptoms and nonspecific abdominal discomfort. In one patient the
      hepatic location was accompanied by a pulmonar location too. The course of the
      patients was good and symptoms subsided with tuberculostatic therapy. To note the
      possibility of finding hepatic tuberculous abscesses in HIV patients with
      prolonged fever and nonspecific abdominal pain more frequently than considered
      until now.

PMID- 7732194
TI  - [Eosinophilic pustular folliculitis in acquired immunodeficiency syndrome. Report
      of 6 cases].
AB  - Eosinophilic pustulous foliculitis (EPF) is a rare dermatosis which has been
      reported in association with the human immunodeficiency virus infection. Six
      patients infected with HIV are reported with advanced disease in whom the
      diagnosis of EPF was made. All patients has a highly pruritic follicular papular
      rash. In all cases the pathology study revealed a mixed inflammatory infiltrate
      with predominance of eosinophils at the infundibulum of the pilous folliculi. Two
      patients had eosinophilia in peripheral blood. Therapy with antihistaminic agents
      and topical corticosteroids was ineffective in all cases. A favourable
      therapeutic response was achieved with phototherapy associated with the topic
      application of disodium cromoglycate 4%.

PMID- 7732195
TI  - [Concept, methods, and usefulness of pharmacologic surveillance: application in
      specialized care].

PMID- 7732196
TI  - [Recent discoveries of cancer genes: what are the consequences for public
      health?].

PMID- 7732197
TI  - [Mortality due to bronchopulmonary cancers in workers of 2 foundries].
AB  - A mortality study was carried out in two factories producing stainless steel in
      order to assess lung cancer risk among workers employed in coke oven, blast and
      open hearth furnaces, foundry, electric furnace, hot and cold rolling mills and
      pickling areas. Occupational exposures of interest were chromium compounds,
      nickel compounds, polycyclic aromatic hydrocarbons (PAH), silica and asbestos.
      All male workers having at least one year of employment between 01.01.1960 and
      31.12.1990 were followed up for mortality. The vital status was assessed from
      birth place registries. Complete job histories since date of first employment
      were abstracted from the company files. The smoking habits of 50% of the cohort
      members were known from medical records. The observed number of deaths (obs) were
      compared with the expected ones based on regional rates with adjustment for age,
      sex and calendar time (Standardized Mortality Ratio, SMR). The cohorts included
      6324 (factory 1) and 5270 (factory 2) workers. The overall mortality did not
      differ markedly from that expected in both factories: SMR = 0.95 (obs = 1540, p =
      0.05) in factory 1 and SMR = 1.06 (obs = 916, non-significant) in factory 2. SMRs
      for lung cancer did not differ from unity, respectively 0.99 (obs = 105) and 1.00
      (obs = 54), in whole cohorts. Non-significant lung cancer excesses were observed
      among workers of some workshops where exposures of interest might have occurred:
      coke oven (SMR = 2.04), blast furnace (SMR = 1.36), open hearth furnace (SMR =
      1.75), hot rolling mills (SMR = 1.29). These processes, however, are no longer
      involved in the study factories. Furthermore, no lung cancer excess was observed
      among workers employed in current workshops: electric furnaces and cold rolling
      mills.

PMID- 7732198
TI  - Recent trends in incidence of cervical cancer in several regions of south-western
      Europe.
AB  - In recent decades, most Western countries have experienced a decline in the
      incidence of invasive cervical cancer. More recently, a reversal of this trend
      has been noted in young women, especially in anglo-saxon countries. These trends
      have been attributed to the beneficial results of cervical cancer screening on
      the one hand, to the widespread increase of high risk sexual behaviors on the
      other. Recent trends in Latin European countries have not previously been
      studied. Time trends of incidence data from 10 regions of South-Western Europe
      (Geneva, Vaud, Calvados, Doubs, Bas-Rhin, Isere, Ragusa, Varese, Zaragoza and
      Navarra) were analysed by means of log-linear models. The data were provided for
      various periods of time between 1970 and 1990. The mean incidence rate varies
      threefold between Navarra where rates are the lowest to Calvados where they are
      the highest. The overall decrease rate is of the order of -3% per year but rate
      changes differ by age group. The reduction seems to concern mostly middle aged
      women. A definite trend could not be determined among younger women due to low
      case numbers. Thus, the hypothesis of a rising incidence in young women cannot be
      confirmed at this time.

PMID- 7732199
TI  - Clinical and psychological classification of non-specific low-back pain. A new
      study in primary care practice.
AB  - This study aimed to explore the clinical and psychological features of non
      specific low-back pain (LBP), and to evaluate a classification of patients based
      on the relationship between psychological disturbances and LBP clinical
      presentation. An unselected population of consecutive patients (n = 262)
      complaining of low-back pain to primary care physicians of the Epidemiology Team
      of the French Rheumatology Society, in October and November 1991, was studied.
      Measures included a standardized clinical evaluation of the back and a
      psychological assessment using the General Health Questionnaire. Ninety nine
      patients (38%) were classified as having a psychological disorder. The following
      symptoms: psychological precipitating event, permanent pain at night, diffuse
      spinal pain, pain increased by changing climate, pain increased by psychological
      factors, dysesthesias in the back, non-anatomical tenderness, were found to be
      closely associated with the existence of psychological disorder. Correspondence
      and cluster analyses provided support for the four-group classification of low
      back pain previously devised. This classification may be interpreted through the
      relationships between psychological disturbances and the back clinical features.
      Although the study was mainly descriptive and used a cross sectional design, its
      results underline the importance of psychological influence on low-back pain
      presentation, and suggest the interest of a psychiatric assessment in low-back
      pain patients. Psychological disorders appear to be frequent in these patients
      and specific management of these disorders may prove useful.

PMID- 7732200
TI  - [Motivations of volunteers for participation in an interventional study in the
      field of nutritional prevention: results of a pilot study of the SU.VI.MAX
      project].
AB  - In this paper, we try to understand the motivations and characteristics of people
      susceptible to be volunteers for the SU.VI.MAX study. The objective of this study
      will be to recruit and to follow during 8 years, a cohort of 15,000 subjects at a
      national level, for an intervention trial in the field of nutritional prevention.
      A short media campaign has been organised to recruit "1,000 volunteers to help to
      test and to validate tools specifically developed for the SU.VI.MAX study". In
      total, 15,789 subjects matching selection criteria answered to our invitation.
      All received a short questionnaire; 10,984 sent back correctly filled up
      questionnaires (70%) and 1005 were selected at random for a complete analysis. A
      lexical analysis of motivations disclosed 6 different groups organised in two
      poles. The pole of true altruists with a speech relative to notions such as
      "volunteers-benevolent" (7% of subjects), wishes to participate to a "humane
      task" (9% of subjects) or to progress of medical research (27% of subjects). The
      other pole corresponds to people interested personally by the theme of the
      project with 3 kinds of speech: personal past history (13% of subjects), interest
      for foods fortified with vitamins and/or minerals (19% of subjects) or for
      relationships between food consumption and health (22% of subjects).

PMID- 7732201
TI  - The role of cooked food mutagens as possible etiological agents in human cancer.
      A critical appraisal of recent epidemiological investigations.
AB  - The paper reviews the epidemiological studies that investigate the relationships
      between dietary protein intake and the risk of some cancer and that have been
      published since 1980. A comparison of these reports is complicated because of
      many confounding factors that could obscure the conclusions (e.g. choice of
      controls) and because it is difficult to distinguish the consumption of fat from
      that of animal proteins. The 75 examined publications deal with the influence of
      food intake on different cancers: colo-rectal (42), stomach (8), breast (7),
      ovarian (4), endometrium (3), prostate (4), pancreas (2), urothelium (1), bladder
      (2), brain (1), lymphoma (1). From these studies in parallel with information
      from other sources, it is concluded that pyrolysis products generated by heat
      treatment of protein-rich food could be responsible factors for, at least, colo
      rectal cancer.

PMID- 7732202
TI  - [A methodological review of specific techniques of time series analysis in
      epidemiology and public health].
AB  - Time series analysis of health indicator can contribute to the improvement of
      knowledge in epidemiology and public health. It is necessary to use models and
      methods appropriate to the time domain. A class of models proposed by Box &
      Jenkins are presented together with the necessary tools for identifying such
      models. Two useful generalisations are also discussed. To study the link between
      two time series, regression models need to include autocorrelated error terms
      while to evaluate the effect of an intervention, the use of intervention models
      are appropriate. This paper presents basic concepts of such analyses in a simple
      way to encourage the use of those methods.

PMID- 7732203
TI  - [Time series analysis of non-typhoid salmonella infections].
AB  - The use of time series modeling for non-typhoidal salmonella infections is
      important for improving epidemiological surveillance. Specific techniques which
      were necessary for our objectives are detailed in an accompanying paper. For each
      series analysed, we discuss how to choose an appropriate statistical model taking
      into account both the data structure and the specific objectives. For salmonella
      infections, we have quantified a "media coverage effect", constructed and alert
      threshold and estimated a link between two series. We have thus shown that the
      analysis of temporal variations is of relevance in public health and can
      contribute to epidemiological knowledge.

PMID- 7732204
TI  - [Feasibility of a familial study on colorectal cancer based on the digestive
      cancer registry of Calvados].

PMID- 7732205
TI  - [Study of anti-loxosceles serum action on hemolytic and ulcero-necrotic cutaneous
      effects of Loxosceles laeta venom].
AB  - The action of an anti-loxosceles serum on in vitro human red blood cell hemolysis
      and on the development of ulcero-necrotic lesions in rabbit skin, induced by
      loxosceles laeta venom, was studied. An 81 +/- 3% hemolysis was obtained after 72
      h incubation of a 2.5% Rh+ red blood cell solution with the equivalent of one
      Loxosceles laeta venom gland. This parameter was not modified adding anti
      loxosceles serum before, along with or after the venom (79.7 +/- 0.8, 77.3 +/-
      2.1 and 80.7 +/- 0.7% respectively). After the intradermic injection of a minimal
      necrotizing venom dose in rabbits, a skin necrotic lesion appeared. This lesion
      did not appear if anti-loxosceles serum was injected together with the venom; if
      the serum was injected one hour after the venom, the resulting skin lesion was
      inflammatory but not necrotic. It is concluded that anti-loxosceles serum does
      not inhibit loxosceles venom induced hemolysis and causes a time dependent
      inhibition on skin necrotic lesions.

PMID- 7732206
TI  - [Natural killer cytolytic activity in renal and prostatic cancer].
AB  - Natural killer cytolytic activity, the basis of cancer immunotherapy that uses
      cytolytic cells, may be impaired in cancer. The aim of this work was to study in
      vitro the natural killer cytolytic activity and its response to the
      immunomodulators interleukin-2, interferon and phytohemagglutinin stimulated
      lymphocyte proliferation in a group of 9 patients with renal cell cancer and 6
      with prostatic cancer. The results were compared with those of 20 normal
      volunteers. Twelve patients were operated and were studied twice 48 h and 14 days
      after surgery. Natural killer cytolytic activity was significantly lower in renal
      cell and prostatic cancer patients than controls (3.3 +/- 1.6, 4.9 +/- 2.2 and
      20.6 +/- 3.7% of specific lysis respectively). This activity was not modified in
      cancer patients by interleukin-2 50 UI/ml or interferon 3000 UI/ml and did not
      differ in the two postoperative periods. Phytohemagglutinin stimulated lymphocyte
      proliferation was also lower in cancer patients, compared to controls
      (stimulation index of 18 +/- 3 and 26.5 +/- 5 respectively). It is concluded that
      these patients have a low immunological level and that this study is the first
      step towards an immunological characterization of cancer patients that are
      candidate to adoptive immunotherapy.

PMID- 7732207
TI  - [Hepatitis B and C virus infections in children with congenital coagulation
      disorders].
AB  - The prevalence of hepatitis B and C virus infections, transmitted by blood
      transfusions, was studied in 79 children with congenital coagulation disorders.
      Twenty nine percent had evidences of hepatitis B virus infection and 52%
      evidences of hepatitis C virus infection. Older children and those with the
      higher number of transfusions had the highest rates of infections. It is
      concluded that children with congenital coagulation disorders constitute a high
      risk group for hepatitis B and C virus infections.

PMID- 7732208
TI  - [Breast cancer and flow cytometry: comparative study of DNA ploidy pattern with
      clinicopathological parameters].
AB  - There is evidence that DNA quantization and histopathological classification of
      breast cancer may be useful for its therapeutic management. DNA flow cytometry,
      clinical and anatomopathological features of 60 paraffin embedded primary breast
      cancer tissue samples were studied. The aneuploidy percentage was 67%. There was
      a correlation between DNA index and degree of cellular pleomorphism, degree of
      differentiation and the fraction of cells in S phase. Likewise a correlation was
      found between the degree of cellular pleomorphism and the mitotic index. DNA
      cytophotometry was useful to solve cases of difficult diagnosis with flow
      cytometry ("near" diploid and tetraploid tumors). No correlation was found
      between aneuploidy, percentage of cells in phase S, degree of cellular atypia and
      mitotic degree with clinical stage, degree of lymph node involvement, tumoral
      size or age. It is suggested that these variables may have an independent
      behavior.

PMID- 7732209
TI  - [Problem based learning: achievement of educational goals in the information and
      comprehension sub-categories of Bloom cognitive domain].
AB  - The aim this work was to assess and compare the achievements of medical students,
      subjected to problem based learning methodology. The information and
      comprehension categories of Bloom were tested in 17 medical students in four
      different occasions during the physiopathology course, using a multiple choice
      knowledge test. There was a significant improvement in the number of correct
      answers towards the end of the course. It is concluded that these medical
      students obtained adequate learning achievements in the information subcategory
      of Bloom using problem based learning methodology, during the physiopathology
      course.

PMID- 7732210
TI  - [Multiple organ failure syndrome in fulminant hepatic failure].
AB  - BACKGROUND: in fulminant hepatic failure, different organs systems become
      involved and a multiple systems organic failure may ensure. AIM: to perform a
      retrospective analysis of patients with fulminant hepatic failure admitted to UC
      Hospital Intensive Care Unit. PATIENTS AND METHODS: the charts of fourteen
      patients (8 male) were analyzed. Multiple systems organic failure was defined as
      the presence of 2 or more organic dysfunctions. The evolution and mortality of
      these patients was analyzed. RESULTS: patient's ages ranged from 30 to 74 years.
      The etiology of hepatic failure was B hepatitis in 4, non A non B hepatitis in 5,
      acute fatty liver of pregnancy in 3 and use of halothane and HIN in 2. ICU stay
      ranged from 1 to 44 days and 2 patients survived (one with drug induced liver
      failure and one with acute fatty live of pregnancy). Mean prothrombin time was 19
      +/- 9.5%, total bilirrubin was 24 +/- 8.9 mg/dl and 12 patients reached grade IV
      encephalopathy. Mean admission APACHE II score was 21.5 +/- 6. Twelve patients
      developed multiple systems organic failure, that appeared 1.5 days after or was
      already present at ICU admission; it lasted a mean of 2.5 days and all these 12
      patients died. Neurologic involvement occurred in 13 patients, renal in 10,
      cardiovascular in 9, respiratory in 5 and hematological involvement in 1.
      CONCLUSIONS: multiple systems organic failure is frequent in fulminant hepatic
      failure and is associated with a high mortality.

PMID- 7732211
TI  - [Radiofrequency fulguration of accessory pathways].
AB  - Between August 1991 and August 1993, 75 patients (42 male) with Wolff Parkinson
      White syndrome (43 concealed) were subjected to radiofrequency ablation of
      accessory pathways at our institution. 55 had left, 8 postero septal, 2
      anteroseptal and 10 right accessory pathways. A retrograde aortic technique with
      placement of the ablation catheter in close proximity to the mitral annulus was
      used for most of the patients with left accessory pathways and for some with
      posteroseptal pathways. The right, anteroseptal and some posteroseptal pathways
      were ablated using a right heart approach placing the ablation catheter in the
      tricuspid annulus. Ablation was successful in 61 patients (81%). One subject
      developed a fatal cardiac tamponade after a transeptal catheterization and was
      unrelated to the ablation per se. It is concluded that radiofrequency ablation of
      accessory pathways is a curative procedure for a great majority of patients with
      Wolf Parkinson White syndrome.

PMID- 7732212
TI  - [Focal and segmental glomerulosclerosis in renal transplantation].
AB  - In 179 patients subjected to 186 renal transplants, 30 renal biopsies were
      performed due to the presence of a proteinuria over 3.5 g/24 h or due to a
      reduction in glomerular filtration rate. Six of these biopsies, coming from 5
      patients, disclosed morphological alterations compatible with focal segmental
      glomeruloesclerosis. Five of these were due to recurrence of the primary disease
      (in four patients) and in all, massive proteinuria appeared from 1 to 23 days
      after transplantation. Two patients with three transplants, evolved to renal
      failure and required dialysis in a period 12 months as a mean. The third patient,
      developed a nephrotic syndrome without renal failure and died 14 months after the
      renal transplant due to a stroke. In the fourth patient, the nephrotic syndrome
      disappeared 38 days after the transplant and remained with minimal proteinuria
      until his last follow up visit two years later. The primary disease of the fifth
      patient is unknown; the nephrotic syndrome appeared 68 months after the
      transplant and remitted spontaneously in 2 months. The renal biopsy showed focal
      and segmental lesions with partial effacement of epithelial foot processes. It is
      concluded that focal segmental glomerulosclerosis recurrence in renal transplant
      occurs with early massive proteinuria and frequently leads to renal failure and
      graft loss in no more than two years.

PMID- 7732213
TI  - [Chronic hemodialysis: program for evaluating the quality of life of patients
      over 60 years old].
AB  - The aim of this work was to assess the quality of life of 87 patients older than
      60 years, out of 200 undergoing chronic hemodialysis in 9 centers at Santiago. A
      visual analog scale, with scores ranging from 0 (bad) to 100 (optimal) and a
      specific questionnaire about the impact of hemodialysis in daily activities, with
      scores ranging from -10 (severe limitation) to +10 (no limitation) were applied
      to patients and their attending nurses. Using the visual analog scale, patients
      assessed their quality of life in 51.7%, and health personnel in 61.3%. Patients
      had a questionnaire score of 2.3. Quality of life scores were inversely
      correlated with the condition of being diabetic and the number of hospital
      admissions.

PMID- 7732214
TI  - [Spontaneous coronary artery dissection in a young woman with acute myocardial
      infarction. Clinical case].
AB  - Spontaneous coronary artery dissection in the absence of atherosclerosis, is a
      rare cause of acute myocardial infarction. We report a 37 years old woman with an
      inferior wall acute myocardial infarction secondary to an spontaneous dissection
      of the right coronary artery. The patient's evolution was uneventful and a new
      angiography performed six months later showed that the dissection persisted. The
      possible etiologies and treatment are discussed.

PMID- 7732215
TI  - [Hemobilia caused by ruptured hepatic artery aneurysm].
AB  - We report two patients with hemobilia caused by hepatic artery aneurism that
      ruptured to the biliary tract. In the first patient, the diagnosis was made
      during an exploratory laparotomy. In the second patient, the aneurism was
      diagnosed with a selective hepatic artery arteriography and embolized during the
      procedure. The evolution of both patients was satisfactory.

PMID- 7732216
TI  - [A case of neutropenia and agranulocytosis induced by clozapine. The importance
      of a drug surveillance program for their early detection].
AB  - Clozapine is an atypical antipsychotic drug with a very low incidence of
      extrapyramidal effects, used in the treatment of schizophrenic patients
      refractory or intolerant to classical neuroleptics. Its use is limited due to the
      potential risk of producing agranulocytosis in 1 to 2% of patients. Despite the
      severity of this complication, the Federal Drug Administration allowed its use as
      long as its prescription is associated to a drug surveillance program that
      controls regularly the white cell count of patients using the drug. Three hundred
      three patients (210 male) have been admitted to a clozapine drug surveillance
      program. Two patients had a transitory leukopenia with less than 2000
      leukocytes/ml and less than 1000 neutrophyls/ml, that reverted after
      discontinuing the drug. One patient, whose case is described, had a severe
      agranulocytosis with less than 500 neutrophyls/ml that required hospital
      admission.

PMID- 7732217
TI  - [Ex vivo procedures associated with autologous hematopoietic stem cell
      transplantation].
AB  - In the last 15 years, autologous cryopreserved bone marrow has been extensively
      used to reestablish hematopoiesis after myeloablative therapies in patients with
      leukemia, lymphomas or solid tumors. Recently, the use of stem cells obtained
      from peripheral blood has become an additional source of autologous stem cells
      for patients, with bone marrow diseases as well as for patients with mammary or
      ovarian cancer, after high dose chemotherapy. The use of this therapy has created
      the need of implementing laboratory procedures (ex vivo) to concentrate, purify,
      cryopreserve and evaluate the hematopoietic stem cell and eliminate tumoral
      cells. This article reviews these procedures, available in Chile at the present
      time, and comments on the impact of its use in autologous bone marrow or
      peripheral blood stem cell transplantations in an estimated population of 300
      patients per year.

PMID- 7732219
TI  - [General medicine: an issue in search of clarity].

PMID- 7732218
TI  - [The Bilbao declaration: international meeting on the law concerning the human
      genome project].
AB  - The Bilbao statement was the result of a work meeting, held the day before the
      closing session by a group of representative experts, formed by general chairmen
      and meeting organizers. The compelled and necessary consent gave rise to the
      document that was read and communicated to the world's public opinion during the
      closing act on may 26, 1993. Notwithstanding, the working group considered that
      the divulged version was provisory and committed to continue the task of re
      elaborating the statement. The aim was to complete and improve it, taking the
      greatest advantage of the important meeting achievements. The document that is
      next reproduced is the definitive integral version of the Bilbao Statement. The
      expert group that takes the responsibility of this Statement is Jean Dausset,
      Nobel Prize of Medicine (1980); Carleton Gajdusek, Nobel Prize of Medicine
      (1976); Santiago Grisolia president of UNESCO committee for the Genome Project;
      Michael Kirby, President of the Court of Appeal of the Supreme Court of New South
      Wales, Australia; Aaron Klug, member of the Constitutional Council, Paris,
      France; Rafael Mendizabal, Judge of the Constitutional Court, Madrid, Spain; Juan
      Bautista Pardo, President of the Superior Court of Justice of the Basque Country
      and Carlos Maria Romeo Casabona, Director of the Chair of Law and Human Genome of
      the University of Deusto (Bilbao).

PMID- 7732220
TI  - [Ethics and the teaching of medicine].

PMID- 7732221
TI  - [Early pregnancy risk: development and validation of a predictive instrument].
AB  - An early pregnancy risk scale, with scores ranging from 11 to 66 points from
      lower to higher risk, was constructed using variables associated with teenager's
      pregnancy. This scale was applied to 3000 female teenagers, coming from
      Metropolitan Santiago public schools. The sample was divided in three risk
      groups: group A (high risk) with scores equal or over 35 points, group B (low
      risk) with scores equal or below 20 points and group B (intermediate risk) with
      scores between 20.1 and 34.9 points. These girls were followed during 2 years.
      During this period, 84 girls became pregnant, 24 of 184 (13%) in group A, 60 of
      2332 (2.6%) in group C and none of 307 in group B. There were 104 school
      desertions in group A and 37 in group B. To study associations and analyze risk,
      the sample was divided in two risk groups: high, with scores over 27 and low,
      with scores below 27. There was a high association between pregnancy risk score
      and the occurrence of pregnancy (RR 5.25 p < 0.0001) and school desertion (RR
      3.32 p < 0.0001). Pregnancy was predicted with a 78% sensitivity and 55.6%
      specificity. School desertion was predicted with a 74% sensitivity and 56%
      specificity. The importance variable weighing using multiple regression models,
      to improve the predictor's sensitivity and specificity, is discussed.

PMID- 7732222
TI  - [Digestive process and regulation of renal excretory function: pepsanurin and
      prokinin inhibit the natriuretic peptide diuretic action].
AB  - In order to clarify the blunting effect of peptides released by pepsin from blood
      plasma on ANP diuretic action, two prokinins designated PU-18 and PU-16 were
      tested. Both of them were able to inhibit in nanomolar doses the diuretic
      saluretic action of 0.5 ug i.v. bolus of ANP given to anesthetized rats either by
      intravenous route or introduced in the duodenal lumen. PU-16 in doses of 0.5 and
      1 ug were able to reduce in 72 and 96.5% respectively the natriuresis induced by
      0.5 ug intravenous bolus of ANP. The data support the hypothesis that prokinins
      liberated in the digestive tract, could be physiological factors involved in
      hydrosaline homeostasis, moderating the ANP mediated increase of water, Na and K
      excretion during digestion.

PMID- 7732223
TI  - [Determination of polychlorinated biphenyls (PCBs) in human milk samples
      collected in 3 provinces of the Tenth Region, Chile. 1990].
AB  - PCBs were detected using gas liquid chromatography in 540 human milk samples
      coming from 180 mothers living in three provinces of the Southern Region of
      Chile, collected in three different stages of lactation. Samples coming from 33
      women (18.3%) had PCBs residues, with a median level of 1.28 (range 0.09-84.83)
      ppm (milk fat basis). Ten of these women delivered to their offspring more than
      0.01 mg of PCB/kg body weight/day, level considered hazardous to child health.
      PCB levels tended to increase toward the third sampling stage. These levels were
      not related to women's age but primiparae had higher levels than multiparae. It
      is concluded that a surveillance system in biological samples is necessary to
      oversee PCB levels in different regions of the country.

PMID- 7732224
TI  - [Gallbladder carcinoma: expression of the c-myc and ras-p-21 oncogene products].
AB  - The expression of c-myc and p-ras-21 oncogenes was studied using an
      immunohistochemical method with monoclonal antibodies in 126 samples of
      gallbladder carcinoma (103 primary tumors and 23 metastatic lesions). Twenty five
      gallbladder samples without tumor evidence were used as controls. C-myc
      oncoprotein was positive in one control sample and p-ras-21 oncoprotein was
      negative in all. Among primary carcinomas c-myc was positive in 9 (9%) and p-ras
      21 in 4 (4%); among metastatic carcinomas c-myc was positive in 6 (26%, p = 0.03
      vs primary carcinoma) and p-ras-21 in 11 (48%, p < 0.001 vs primary carcinoma).
      There was a non significant association between c-myc and p-ras-21 expression and
      degree of histological differentiation and level of tumoral infiltration. It is
      concluded that c-myc and p-ras-21 oncoprotein expression is observed in less than
      10% of primary gallbladder carcinomas and that this expression is significantly
      higher in metastatic carcinomas. This may reflect an activation or overexpression
      of these oncogenes in metastatic cells.

PMID- 7732225
TI  - [Characterization of Neisseria meningitidis isolated fron systemic infections.
      Chile, 1992-1993].
AB  - BACKGROUND: in Chile, all systemic infections caused by Neisseria meningitidis
      must be reported and the bacterial strain must be sent to a Reference Laboratory
      at the Instituto de Salud Publica de Chile (ISP). AIM: to report the
      characterization of strains of N. meningitidis isolated during systemic
      infections in Chile during the years 1992 and 1993. METHODS: the serogroup,
      serotype, subtype and antimicrobial susceptibility of every strain of N.
      meningitidis received at the ISP during 1992 and 1993 was studied. RESULTS: six
      hundred twenty eight strains of N. meningitidis were confirmed during 1992 and
      1993. B serogroup was responsible of 91.1% and 94.7% of confirmed cases during
      1992 and 1993 respectively. Serotypes and subtypes most frequently associated to
      B serogroup were B: 15: P1.3 (63.2%) in 1992 and 51.8% in 1993) and B:NT:P1.3
      (11.7% in 1992 and 21.3% in 1993). In 1992, all strains were susceptible to
      penicillin, chloramphenicol, ceftriaxone and rifampicin. During 1993, 7 (2%)
      strains were found, for the first time in Chile, moderately susceptible to
      penicillin and rifampicin MIC90 increased fourfold in respect of 1992, although
      all strains continued to be susceptible to this antimicrobial. CONCLUSIONS: the
      increasing frequency of NT (non typified strains) isolation will demand the use
      of molecular biology techniques for their identification. The appearance of
      penicillin resistant strains in our country is worrisome.

PMID- 7732226
TI  - [Pituitary tumors: clinical presentation and evaluation of transphenoidal
      surgical treatment].
AB  - The clinical manifestations and the surgical treatment results of 280 patients
      (179 female), undergoing a total of 319 operations at the Asenjo Institute of
      Neurosurgery were retrospectively analyzed. The surgical approach for the first
      operation was transphenoidal in 89.3% of patients and transcraneal in the rest.
      Tumors were non-secretory in 169 (60.4%) patients, prolactinomas in 75 (27.8%)
      and produced acromegalia in 29 (10.4%) and Cushing syndrome in 7 (2.5%) patients.
      There was extraselar extension in 42% of women and 71% of men. The surgical
      treatment of prolactinomas corrected endocrine alterations in 25 of 29 and visual
      alterations in 18 of 27 patients assessed. Surgical treatment of acromegalia
      improved endocrine alterations in 11 of 13 and visual alterations in 4 of 10
      patients assessed. Treatment of non secretory tumors corrected visual alteratons
      in 38 of 64 patients assessed. The principal complication of transphenoidal
      surgery was transient diabetes insipidus in 6.8% of patients. Overall mortality
      was 2.3% for transphenoidal surgery and 5.6% for transcraneal surgery. It is
      concluded that transphenoidal surgery is effective for the management extraselar
      complications of pituitary tumors and endocrine management of selected cases.

PMID- 7732227
TI  - [Non ulcerative dyspepsia: relationship of symptomatology, gastritis and
      Helicobacter pylori].
AB  - BACKGROUND: histological alterations of gastric mucosa and its colonization by
      Helicobacter pylori are postuled to be implicated in the pathogenesis of non
      ulcer dyspepsia. AIM: to study the possible relationships between histological
      gastritis and Helicobacter pylori in non ulcer dyspepsia symptomatology. PATIENTS
      AND METHODS: fifty four patients (39 females) with non ulcer dyspepsia whose ages
      ranged from 17 to 68 years were subjected to an upper GI endoscopy with gastric
      mucosa biopsy samples for histological study and microbiological identification
      of Helicobacter pylori. Gastrointestinal complains were blindly quantified using
      a scored questionnaire. RESULTS: thirty one subjects (57.4%) had Helicobacter
      pylori in their gastric mucosa. There was acute inflammatory activity in 26 of
      the 31 patients with Helicobacter pylori (81%) and 15 of 23 without Helicobacter
      (65%). The median score of symptoms was 7 (range 2-13) in patients with
      Helicobacter and 6 (range 2-10) in patients without Helicobacter. CONCLUSIONS:
      there were no significant differences in gastric mucosa acute inflammatory
      activity and non ulcer dyspepsia symptomatology between patients with or without
      Helicobacter pylori colonization of gastric mucosa.

PMID- 7732228
TI  - [Cysts of second branchial cleft: review of 32 operated cases].
AB  - The aim of this work was to analyze retrospectively the clinical features of 32
      patients aged 23.9 years (21 female) with the histological diagnosis of second
      branchial cleft cyst. In 28 patients, the cyst was localized below the mandibular
      angle. The presenting symptom was a cervical tumor in 30 patients and pain in
      eight. Fourteen aspiration punctures was performed obtaining 8 purulent and 6
      straw colored aspirates. The preoperative diagnosis was correctly made in only 19
      patients; the principal confounding diagnosis was tuberculous adenitis. All
      patients were operated performing a complete cystectomy in 30 and partial
      cystectomy in two. Three patients had a surgical wound infection and the cysts
      recurred 5 months and 4 years after operation in the two patients subjected to
      partial cystectomy. The histological study revealed squamous epithelial with
      underlying lymphoid tissue. It is concluded that aspiration puncture is useful
      for the correct diagnosis and that the cyst must be completely eradicated to
      avoid recurrences.

PMID- 7732229
TI  - [Bacterial infections in hepatic cirrhosis].
AB  - The aim of this work was to study the prevalence of bacterial infections in
      hospitalized patients with liver cirrhosis and to compare clinical,
      bacteriological and evolution features of patients with (group 1) and without
      bacterial infections (group 2). One hundred thirty two hospitalized patients with
      liver cirrhosis were prospectively studied and 61 episodes of bacterial
      infections were diagnosed in 52 (27 spontaneous bacterial peritonitis (44.3%), 16
      urinary tract infections (26.2%), 10 pneumonias (16.4%), 3 spontaneous
      bacteremias (4.9%9, and 5 miscellaneous infections (8.2%)). Twenty six percent of
      infections were nosocomial. Child-Pugh score was 12 +/- 2 in group 1 vs 10 +/- 2
      in group 2 (p = 0.047). Sixty five percent of identified microorganisms were gram
      negative and 61.5% of these were E. coli. Hospital mortality of group 1 was 29%
      and that of group 2 was 9% (p = 0.002). It is concluded that there is a high
      prevalence of bacterial infections in hospitalized cirrhotic patients, that is
      associated to a high mortality.

PMID- 7732230
TI  - [Mushroom poisoning in the IX region. Role of Amanita gemmata].
AB  - We report four episodes of mushroom poisoning that occurred between 1986 and 1990
      in the province of Malleco. Twenty five of 36 individuals who ingested the
      mushroom became ill; they had an acute gastroenteritis that was followed in 7 by
      an acute hepatitis and in one by a massive upper gastrointestinal bleeding. Three
      subjects with fulminant hepatic failure and the subject with the massive bleeding
      died. Amanita gemmate (strain described as toxic in Chile since 1967) was found
      in two episodes and Amanita sp in one. The clinical picture is similar to that
      described for Amanita phaloides. The treatment is symptomatic but penicillin and
      silymarin may have an antitoxic action. The importance of warning the population
      about the existence of toxic mushrooms in Chile is emphasized.

PMID- 7732231
TI  - [Hypothermia: a non renal indication for peritoneal dialysis].
AB  - Accidental hypothermia, a condition seldomly seen in Chile, is defined as a
      spontaneous core temperature reduction to less than 35 degrees C and is
      associated with great morbidity and mortality. We report a 16 years old female
      intoxicated with liquefied petroleum gas that was admitted in coma, hypothermic,
      with severe hemodynamic derangement, lactic acidosis, rhabdomyolysis and
      iliofemoral phlebothrombosis. Peritoneal dialysis with solutions at 27 degrees C
      was used as a quick and safe means to revert hypothermia and avoid its
      complications.

PMID- 7732232
TI  - [Renal and respiratory failure in a pregnant woman with progressive systemic
      sclerosis. Anatomo-clinical case].
AB  - Pregnancy in patients with systemic sclerosis may predispose to a fast
      progression of the disease. We report a woman with systemic sclerosis and
      multiple visceral involvement that during the third trimester of pregnancy
      developed a respiratory failure caused by interstitial fibrosis complicated with
      alveolar hemorrhage, bronchopneumonia and respiratory distress syndrome and a
      renal failure. On admission, she was subjected to a cesarean section, delivering
      a 1205 g newborn. In spite of intensive care support, the multisystemic failure
      became unmanageable and the patient died 15 days after admission. Literature
      review, although sometimes controversial, indicates that pregnancy is a situation
      with a definitive death risk for patients with systemic sclerosis, that requires
      a close follow up.

PMID- 7732233
TI  - [Hodgkin's disease: relapse after 16 years of continuous remission].
AB  - We report a boy in whom and advanced Hodgkin's disease, nodular sclerosis
      variety, was diagnosed at 5 years of age and treated with exclusive chemotherapy.
      After 16 years of remission, he presented with a relapse of the disease, with a
      different histological pattern and was subjected to chemotherapy (C-MOPP/AVB) and
      unilateral axillary irradiation, obtaining a complete remission of the disease.
      Four months later, the patient is asymptomatic and without evidences of relapse.

PMID- 7732234
TI  - [Papillary cystic tumor of the pancreas: an infrequent carcinoma of good
      prognosis].
AB  - Papillary cystic tumor of the pancreas is a rare low grade carcinoma, with only
      130 cases reported in the English literature. We report a 22 years old female
      presenting with a palpable mass and abdominal pain. Abdominal ultrasound and CAT
      scan showed a solid-cystic lesion in the head of the pancreas. The patient was
      subjected to a partial pancreatoduodenectomy and the histological study of the
      surgical specimen disclosed a papillary cystic carcinoma. Post op course was
      uneventful and the patient is well at 8 months follow up.

PMID- 7732235
TI  - [Ethical principles in human scientific research].
AB  - Hippocrates was the first physician to use the scientific method to find rational
      and not religious or mythic causes, for the etiology of diseases. Hippocrates and
      Aristoteles did not dare to dissect the human body. Afterwards however, many
      scientists such as Herophilus, Erasitastrus, Vesalus and Fallopio, performed
      experiments in human beings using vivisection. According to that age's ideas,
      there was no cruelty in performing vivisection in criminals, since useful
      knowledge for the progress of medicine and relief of diseases was obtained. Only
      during the nineteenth century and with Claude Bernard (1865), the ethical
      principles of systematic scientific research in humans were defined. These
      principles were violated by nazi physicians during Hitler's dictatorship in
      Germany (1933-1945). As a response to these horrors, the Ethical Codes of
      Nuremberg (1947) and Geneva (1948), that reestablished all the strength of
      Hippocratic principles, were dictated. The Nuremberg rules enact that a research
      subject must give a voluntary consent, that the experiment must by necessary and
      exempt of death risk, that the research must be qualified and that the experiment
      must be discontinued if there is a risk for the subject. The Geneva statement is
      a modernized hippocratic oath that protects patient's life above all. These
      classical rules, in force at the present time, are the essential guides that must
      be applied by physicians and researchers.

PMID- 7732236
TI  - [Computer assisted codification of diagnosis. Experience in a
      neurology/neurosurgery service].
AB  - The aim of this report is to show a dBase III+based program designed to assign
      the International Classification of Diseases codes to medical diagnoses. The
      principal features, advantages and limitations diagnoses. The principal features,
      advantages and limitations of the program are depicted and its yield with
      different users in a Neurology and Neurosurgery department is analyzed. It is
      concluded that this is a user friendly software with minimal hardware
      requirements that can be used in any clinical setting.

PMID- 7732237
TI  - [Education-assistance relationship: local education-assistance +commissions
      (COLDAS), a mutual need?].

PMID- 7732238
TI  - [Hemorrhoids and hemorrhoidal disease: current concepts].

PMID- 7732239
TI  - [Microsporidiosis in patients with AIDS and chronic diarrhea].

PMID- 7732240
TI  - [Day care attendance: impact on acute lower respiratory disease in children under
      2 years old].
AB  - AIM: To measure the impact of day care attendance on lower respiratory tract
      infections in children under two years old in two urban settings with different
      degrees of air pollution. SUBJECTS AND METHODS: A 26 week follow up, during fall
      and winter of 1991 and 1992, was performed to 98 children (48 attending day care
      and 50 controls) coming from Santiago, a city affected by severe air pollution
      and 95 children (46 attending day care and 49 controls) coming from San Felipe
      and Los Andes (villages with low air pollution). The incidence of lower
      respiratory infections was recorded by trained personnel and expressed as rates
      per 100 weeks of follow up. Day care settings in San Felipe and Los Andes were
      state funded whereas those from Santiago were private. All premises had wooden or
      plastic floors and smoking was forbidden. During the follow up years, no
      respiratory epidemics were recorded. RESULTS: The socioeconomic level of children
      from San Felipe and Los Angeles was better. Children from Santiago were more
      exposed to tobacco smoke. The highest incidence of lower respiratory infections
      was found in children attending day care in San Felipe and Los Andes (31.2
      episodes/100 weeks of observation), closely followed by control and day care
      attending children from Santiago (28.7 respectively) and control children from
      San Felipe and Los Andes (18.2). CONCLUSIONS: Day care attendance in areas with
      low air pollution increases the risk of lower respiratory infections. Instead, in
      highly polluted areas, the infection rates do not increase.

PMID- 7732242
TI  - [What is your diagnosis? Erosive osteochondrosis].

PMID- 7732241
TI  - [Dr. Miguel Oyonarte Gomez, president of the Medical Society of Santiago].
AB  - In October, 1993, Dr. Miguel Oyonarte started his 2-year term as President of
      Sociedad Medica de Santiago (Chilean Internal Medicine Association). Dr.
      Oyonarte, Professor of Medicine at the University of Chile School of Medicine and
      Chairman of the Department of Internal Medicine (Central Campus), Hospital San
      Borja-Arriaran, is a certified internist and a distinguished cardiologist, with
      post-graduate training in Liverpool, UK, and in the USA. The first enterprise
      that Dr. Oyonarte successfully achieved during his mandate was to set up the new
      building for the Sociedad, recently inaugurated with the presence of the
      President of the Republic and the Minister of Health.

PMID- 7732243
TI  - [Sleep and dreams in pictures].
AB  - Human life is divided into two thirds wakefulness and one third sleep. A newborn
      child sleeps to strengthen, the adult for regeneration. At the end of life man
      sinks down into the sleep of death: Hypnos and Thanatos are twin sons of the
      Queen of Night. Myths from different cultures are influenced by the experience of
      sleep and its inner world of pictures, the dreams. Artists, painters and
      sculptors let their visions float steadily into new pictures, and creatures of
      sleep formed out of diverse materials. Devine sleep, sleep for new life, sleep of
      health, creative sleep, prophetic sleep, sleep for revelation and for decisions.

PMID- 7732244
TI  - [Pathophysiology of sleep].
AB  - Disturbed sleep is a frequent concomitant of depression and of normal aging.
      Simultaneous investigations of sleep EEG and of nocturnal hormone secretion
      reveal that under both conditions slow-wave sleep and growth-hormone secretion
      decrease and sleep continuity is disturbed in comparison to younger normal
      controls. Animal studies and recent data from investigations in our laboratory in
      young and elderly normal controls and in patients with depression demonstrate
      that the neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin
      releasing hormone (CRH) are common regulators of peripheral hormone secretion and
      of sleep structure. We suggest that changes of the ratio between both peptides
      play a key role in the pathophysiology of sleep endocrine aberrations during
      aging and depression.

PMID- 7732245
TI  - [Sleep disorders and their treatment].
AB  - Disturbed or inadequate sleep is a frequent complaint, often with a chronic
      course, requiring adequate treatment. To choose an appropriate therapy it is
      necessary to develop a useful, reliable valid and specific diagnostic procedure.
      Primary care physicians can recognize and treat most sleep disorders. For special
      diagnostic cases sleep centers are recommended. Sleep disorders may be managed by
      adequate pharmacological as well as nonpharmacological treatments. Besides
      specific pharmacological interventions, education in sleep/wake hygiene and
      several psychotherapeutic strategies may be valuable.

PMID- 7732246
TI  - [Sleep and addiction].
AB  - Sleep disorders and depressive symptoms are concomitant features in patients with
      addictive disorders. In this study, patients with addiction (alcohol and opioid,
      resp.) and with major depression (DSM-III-R) were examined with a sleep EEG and
      compared to age-matched controls. An age-dependent decrease of total sleep time
      and slow-wave sleep (SWS) was demonstrated. Sober patients with alcohol
      dependency showed a decrease of SWS, whereas patients with opioid dependency
      substituted with methadone showed a disorder of REM sleep (REM suppression).
      Depressive patients revealed a disturbance of sleep continuity and REM sleep
      (increased REM sleep). The neurobiological differentiation by sleep EEG is of
      interest for research and clinical practice.

PMID- 7732247
TI  - [What is your diagnosis? Hypertrophic cardiomyopathy].

PMID- 7732248
TI  - [Sleep and respiration].
AB  - Nocturnal sleep-associated breathing disorders have only been investigated
      thoroughly since about 15 years. From these studies it became clear that many
      respiratory disorders, in particular chronic obstructive ones, may severely
      impair nocturnal breathing and thus oxygen supply. by physiologically reduced
      ventilation at night, particularly in patients with already reduced pulmonary
      function, oxygen supply may become insufficient. In order to prevent late
      sequelae, early invalidity or precocious death, a comprehensive diagnostic
      approach is mandatory. Therapy consists of thorough anti-obstructive and anti
      inflammatory inhalations, aided by additional oxygen supply during the night
      sleep in selected cases. Sleep-apnea syndrome is a frequent disease. About 3%, of
      males between 25 and 75 and at least 1% of females particularly after menopause,
      are affected. In most cases diagnosis can be suspected by clinical symptoms and
      nocturnal pulse oximetry. Sensitivity of pulse oximetry, however, is
      insufficient, thus polysomnography is necessary to establish the diagnosis and to
      control therapy. The most important therapeutic measure is to establish a
      nocturnal nasal continuous positive airway pressure (nCPAP) that may lead to
      immediate amelioration of symptoms and may normalize survival of patients. In
      particular, patients with obstructive sleep apnea should not drive motorized
      vehicles because of their excessive daytime sleepiness until a therapeutic
      success is evident. In this paper chronic obstructive pulmonary diseases, the
      central and the obstructive sleep-apnea syndrome are covered in particular.

PMID- 7732249
TI  - [Role of ENT surgery in the assessment and treatment of snoring and of
      obstructive sleep apnea syndrome in adults and children].
AB  - The otolaryngologist is increasingly involved in the evaluation and management of
      sleep-related respiratory disorders. Main symptoms of intermittent obstruction in
      adults and children are snoring and stridulous breathing. Important factors
      causing pharyngeal obstruction are functional and structural narrowings in the
      upper airways leading to increased upstream resistance. The ENT's examination has
      two principal aims: 1. habitual snoring must be separated from an obstructive
      sleep-apnea syndrome (OSAS), as the later is associated with cardiovascular
      diseases and an increased mortality; 2. a functional or structural cause of the
      obstruction must be sought. Flexible nasopharyngoscopy is a valuable diagnostic
      tool to determine the nature of obstruction. OSAS patients need a differentiated
      evaluation in a sleep laboratory, and an attempt of therapy with continuous
      positive airway pressure (CPAP) should be undertaken in most of these cases.
      Today the otolaryngologist is equipped with a whole range of conservative and
      surgical therapeutic possibilities. The introduction of compact lasers as well as
      the endoscopic/microscopic endonasal surgery have revolutionized surgical
      treatment in patients with habitual snoring and OSAS. In contrast to adults, OSAS
      in children has still received poor attention and leads often to impaired
      thriving. Most frequently, hypertrophied tonsils are present, and tonsillectomy
      eliminates obstruction in nearly all of these cases.

PMID- 7732250
TI  - [Sleep and sleepers in literature].
AB  - Sleep sets specific limits to self-control or self-disposal of man. Freud's
      statement that one third of our own self is still unborn points to a certain
      amount of uncertainty, linked permanently to our existence during sleep and
      associated with our loss of control over our rational thinking. Therefore, in the
      literature, sleep is quite often correlated with mythic, magic and religious
      conceptions. In particular, the experience of innocence is compellingly linked to
      sleep, necessarily followed by the question of guilt and evil. Goethe describes
      sleep as a process of working up and surmounting guilt as a basic event of
      spiritual and physical healing. Shakespeare's Macbeth, however, shows from an
      archaic-mystical as well as a modern psychological view how sleep is destroyed by
      crime.

PMID- 7732251
TI  - [A case from practice (323). 1. Chronic alcohol abuse 2. Adenocarcinoma of the
      sigmoid colon 3. Increase in Ca-125 of unclear origin].

PMID- 7732252
TI  - [Pelvic pain related to pelvic ligament support].
AB  - In the context of organic pelvic pain, alongside post-infectious pain or pain
      related to endometriosis, ruptured ligaments of the pelvic fascia are an
      important cause of the pelvic congestion syndrome well known to classical
      authors. Surgical treatment combines two procedures: suture of the tear and
      exclusion of the pouch of Douglas.

PMID- 7732253
TI  - [Painful pelvic adhesion syndrome].
AB  - Pelvic adhesions may be responsible for pelvic pain, at least partially, in the
      following conditions: sequelae of past infection, chronic active inflammatory
      state, endometriosis, post-operative adhesions. The problem in the presence of
      adhesions is to determine whether pain is mechanical, inflammatory and/or linked
      to associated ovarian dystrophy, and what is the psychological component. The
      postulate "adhesion = pain" is far from constant and there is no systematic
      relationship between clinical picture and anatomical findings. After careful
      clinical and laboratory evaluation, celioscopy is the key diagnostic procedure.
      It should include thorough examination of all pelvic organs, of the abdomen in
      general and the peri-hepatic region in particular. A diagnosis of psychosomatic
      pain can be made only in the absence of any macroscopic, histological and
      bacteriological lesion, though bearing in mind that this term certainly covers
      failure to recognise other causes.

PMID- 7732254
TI  - [Pelvic pain and endometriosis].
AB  - Endometriosis is defined by the presence outside the uterine cavity of tissue
      histologically and functionally similar to the endometrium. Endometriosis
      consists of glands and an underlying cytogenic stroma. This ectopic tissue can
      react to hormonal stimulation: estrogens and progesterone (growth,
      decidualisation, withdrawal bleeding). Pain is correlated with the depth of
      implantation of endometriosis lesions. Deeply infiltrating endometriosis exceeds
      6 mm in depth, with an incidence of between 6 and 20% of women complaining of
      pelvic pain. The authors review the various types of treatment and mention the
      special role of celio-surgery and prolonged hormone therapy.

PMID- 7732255
TI  - [Congestive pelvic syndromes].
AB  - Pelvic congestion syndrome is encountered in three pathological situations:
      premenstrual syndrome, intermenstrual syndrome, chronic pelvic congestion
      syndrome. The first two syndromes, with a range of physical and/or psychological
      symptoms, are cyclical. Their pathogenesis is multifactorial. Hormonal and
      circulatory factors are essentially blamed. Treatment is most often based upon
      combinations of progestogens and venotonics. The third syndrome, that of chronic
      pelvic congestion, is characterised by long term pelvic pain and raises
      etiopathogenic problems which remain only partially solved and in which a
      vascular role may sometimes be recognised. Endovaginal ultrasonography with
      colour-coded Doppler and celioscopy sometimes reveal pelvic varicose veins and
      indicate their responsibility for such pain, after having eliminated specific
      pelvic pathology (post-infectious or post-operative inflammatory sequelae of
      pelvic tissue, rupture of the broad ligaments, endometriosis, etc.). Treatment is
      above all medical, based upon hormone therapy acting upon venous receptors,
      venotonics which decrease the consequences of stasis, intermittent courses of
      anti-inflammatory agents and antibiotics when there is inflammation secondary to
      local infection. These various types of treatment may be combined. Surgical
      treatment should be restricted to certain carefully assessed cases only.

PMID- 7732256
TI  - [Hypertrophic tuberculosis of the cervix].
AB  - The authors report two cases of tuberculosis of the uterine cervix. They point
      out the exceptional nature of this form of genital tuberculosis, and its
      epidemiological aspects. They stress that its macroscopic appearance is highly
      suggestive of a carcinomatous lesion. Doubt can be eliminated only by cervical
      biopsy and appropriate treatment for tuberculosis can then be started. Surgery is
      only very rarely required.

PMID- 7732257
TI  - [Clinical trials in homeopathy: treatment of mastodynia due to premenstrual
      syndrome].

PMID- 7732258
TI  - [3rd Francophone congress on coleosurgery. Deauville, April 6-7, 1995.
      Abstracts].

PMID- 7732259
TI  - Evaluation of phenotypic markers associated with pathogenicity in the genus
      Listeria.
AB  - A total of 130 Listeria strains were tested in order to evaluate lecithinase
      production and capacity for Congo red adsorption as markers of pathogenicity. The
      strains were identified according to acid production from sugars and by the CAMP
      test and the data were correlated with the ability to produce
      keratoconjunctivitis in guinea pigs. L. monocytogenes cultures presented 51.8%
      and 88.8% positivity rates for Congo red adsorption and lecithinase production,
      respectively, whereas 80.8% and 100% for L. innocua cultures were negative for
      the two test, respectively.

PMID- 7732260
TI  - Induction of iron regulated proteins during normal growth of Neisseria
      meningitidis in a chemically defined medium.
AB  - The expression of iron regulated proteins (IRPs) in vitro has been obtained in
      the past by adding iron chelators to the culture after bacterial growth, in the
      presence of an organic iron source. We have investigated aspects concerning full
      expression of the meningococcal IRPs during normal growth, in defined conditions
      using Catlin medium, Mueller Hinton and Tryptic Soy Broth (TSB). The expression
      of IRPs varied between different strains with respect to Ethylenediamine Di-ortho
      Hidroxy-phenyl-acetic acid (EDDA) concentrations, and according to culture
      medium, and also between different lots of TSB. For each strain, a specific set
      of IRPs were expressed and higher EDDA concentrations, or addition of glucose, or
      use of different culture media did not resulted in a differential expression of
      IRPs. We were not able to grow N. meningitidis under normal growth conditions
      using Desferal. We looked for a good yield of outer membrane vesicles (OMVs)
      expressing IRPs in iron-deficient Catlin medium containing EDDA and Hemin.
      Culture for 32 h at 30 degrees C after growing for 16 h at 37 degrees C supported
      good bacterial growth. Bacterial lysis was noted after additional 24 h at 30
      degrees C. Approximately 4 times more OMVs was recoverable from a culture
      supernatant after 24 h at 30 degrees C than from the cells after 16 h at 37
      degrees C. The IRP were as well expressed in OMVs from culture supernatant
      obtained after 24 h at 30 degrees C as from the cells after 16 h at 37 degrees C.

PMID- 7732261
TI  - [Feeding pattern of Triatoma rubrovaria (Blanchard, 1843) (Hemiptera,
      Triatominae) in peridomiciliary habitats, of a rural area of Uruguay].
AB  - It has been studied the feeding patterns of Triatoma rubrovaria (wild triatominae
      bug, and intradomiciliary secondary vector of T. cruzi) in a rural area of "La
      Bolsa" (Department of Artigas). Agar double diffusion test were used for analyze
      the blood meal, from 120 insects, which were confronted to 13 antisera. It has
      251 identify blood meals, and the most frequently was mammalian host (73%), but
      it has a variable source of feeding (mammals, birds, reptiles and cockroach),
      including humans rate 8% of the total. The identify of haemolimphe as feed, place
      this triatominae bug as an intermediary vector between predator and
      haematophagous. The most usual mammals are dasypodides and bovines. The frequence
      of human blood meal near the dwellings, shows its potentiality as vectors.
      Therefore, the peridomicile is an area of interaction between, domestic, wild and
      sinantropic host. The trypanosomic infection's rate at peridomiciles was lesser
      those at wild areas.

PMID- 7732262
TI  - Schistosoma mansoni circulating polysaccharide and protein antigens recognized by
      sheep antisera in patients with different clinical forms of schistosomiasis
      before and after treatment.
AB  - Two sheep antisera, one of which raised against polysaccharide (Po) and other
      against protein (Pt) components of Schistosoma mansoni adult worms, were assessed
      by ELISA for their ability to detect circulating parasite antigens in patients
      with different clinical forms of chronic schistosomiasis mansoni. The former
      antiserum detected parasite antigens in liver granulomata and the latter in renal
      glomeruli from schistosomiasis patients and mice experimentally infected with S.
      mansoni. In general, the levels and/or positivity rate of circulating antigens
      and specific IgG antibodies were significantly higher in patients with
      hepatointestinal (HI) and hepatosplenic (HS) forms than in mild intestinal (I)
      forms. An association between Po antigens and clinical features of the disease
      was observed, as the level of these antigens was low (137 ng/ml) as well as the
      positivity rate (7.9%) in patients with I forms; values that were intermediate
      (593 ng/ml and 33.3%) in those with HI forms, and high (1.563 ng/ml and 50.0%) in
      more severe HS forms. The Pt antigens were detected in the studied clinical forms
      not differing statistically but, the positivity rate was significantly higher in
      HS forms comparatively to I forms. The antisera studied revealed distinct
      circulating antigen profiles, and the prognostic value of Po and Pt antigens was
      suggested.

PMID- 7732263
TI  - The diagnostic importance of species specific and cross-reactive components of
      Taenia solium, Echinococcus granulosus, and Hymenolepis nana.
AB  - Sera from patients infected with Taenia solium, Hymenolepis nana and Echinococcus
      granulosus were tested against homologous and heterologous parasite antigens
      using an ELISA assay, and a high degree of cross-reactivity was verified. To
      identify polypeptides responsible for this cross reactivity, the Enzyme Linked
      Immunoelectro Transfer Blot (EITB) was used. Sera from infected patients with
      T.solium, H.nana, and E.granulosus were assessed against crude, ammonium sulphate
      precipitated (TSASP), and lentil-lectin purified antigens of T.solium and crude
      antigens of H.nana and E.granulosus. Several bands, recognized by sera from
      patients with T.solium, H.nana, and E.granulosus infections, were common to
      either two or all three cestodes. Unique reactive bands in H.nana were noted at
      49 and 66 K-Da and in E.granulosus at 17-21 K-Da and at 27-32 K-Da. In the crude
      cysticercosis extract, a specific non glycoprotein band was present at 61-67 K-Da
      in addiction to specific glycoprotein bands of 50, 42, 24, 21, 18, 14, and 13 K
      Da. None of the sera from patients with H.nana or E.granulosus infection cross
      reacted with these seven glycoprotein bands considered specific for T.solium
      infection.

PMID- 7732264
TI  - [Neurologic and laboratory findings in a population of an endemic area for
      taeniasis-cysticercosis, Lagamar, MG, Brazil (1992-1993)].
AB  - A clinic-epidemiological enquiry was conducted on in an endemic area for teniasis
      cysticercosis. From the whole population 1080 (32.2%) individuals were examined.
      We found 198 (18.3%) individuals referring teniasis-bearing in the past, and 103
      (9.5%) affirming to have had convulsions, either in the past or present. From the
      last group, 39 (37.8%) indicated that the crisis had begun in adulthood. From the
      group of patients presenting convulsions, 62 (62%) had laboratory tests
      performed. Computed tomography showed intracranial calcifications in 21 (33.8%)
      patients, variable in number and location, suggesting neurocysticercosis and no
      evidence of disease activity. Electroencephalograms showed abnormal waves in 21
      (33.8%) patients and cerebrospinal fluid analyses were altered in 27 (43.5%)
      cases, having detected eosinophils only in 3 (4.8%) patients. Spinal fluid tests
      for cysticercosis through enzyme linked immunosorbent assay (ELISA) or indirect
      immunofluorescence were taken in only 26 (41.9%) patients, obtaining positive
      results in 6 (23%) samples. Varying upward shifts of protein levels were found in
      spinal fluid analysis. Assuming that all epidemiologic risk factors for teniasis
      cysticercosis in the studied region and its correlation with the laboratory
      alterations described in convulsing crisis, a prevalence of 1.9% for
      neurocysticercosis was found.

PMID- 7732265
TI  - [Current status of the eco-epidemiological knowledge on arboviruses pathogenic to
      humans in the Atlantic Forest region of the State of Sao Paulo].
AB  - The available eco-epidemiologic information on pathogenic arbovirus to humans in
      the Atlantic Forest region of the State of Sao Paulo were analysed. According to
      this information arbovirus transmission cycles are proposed.

PMID- 7732266
TI  - Sonographic features of portal hypertension in schistosomiasis mansoni.
AB  - The diagnostic value of real-time sonography in the study of portal hypertension
      was assessed in 66 patients with hepatosplenic schistosomiasis mansoni, all with
      Symmers's fibrosis and esophageal varices. Seventy-one individuals without
      schistosomiasis were selected as controls. The inner diameters of the portal
      vessels were measured by sonography in all patients and controls:
      splenoportography was also performed in the schistosomal group. Intra-splenic
      pressure was over 30 cm of water in 44 of 60 patients with schistosomiasis. The
      upper limit of normality for portal vessel diameters was set through receiver
      operating characteristic curve at 12 mm for portal vein, 9 mm for splenic vein at
      splenic hilus, and 9 mm for superior mesenteric vein. The best discriminative
      vein for the diagnosis of portal hypertension was the splenic vein followed by
      the portal vein. A direct correlation was observed between the diameter of the
      splenic vein, measured by sonography, and the intra-splenic pressure. Except for
      the paraumbilical and mesenteric veins, more frequently identified by sonography,
      there was no statistical difference in the frequency of visualization of
      splanchnic vessels by sonography or splenoportography.

PMID- 7732267
TI  - Chagas' disease in the Brazilian Amazon. I--A short review.
AB  - At least eighteen species of triatominae have been found in the Brazilian Amazon,
      nine of them naturally infected with Trypanosoma cruzi or "cruzi-like"
      trypanosomes and associated with numerous wild reservoirs. Despite the small
      number of human cases of Chagas' disease described to date in the Brazilian
      Amazon the risk that the disease will become endemic in this area is increasing
      for the following reasons: a) uncontrolled deforestation and colonization
      altering the ecological balance between reservoir hosts and wild vectors; b) the
      adaptation of reservoir hosts of T. cruzi and wild vectors to peripheral and
      intradomiciliary areas, as the sole feeding alternative; c) migration of infected
      human population from endemic areas, accompanied by domestic reservoir hosts
      (dogs and cats) or accidentally carrying in their baggage vectors already adapted
      to the domestic habitat. In short, risks that Chagas' disease will become endemic
      to the Amazon appear to be linked to the transposition of the wild cycle to the
      domestic cycle in that area or to transfer of the domestic cycle from endemic
      areas to the Amazon.

PMID- 7732268
TI  - Relationship between acute malaria and anti-RESA antibodies in sera of patients
      from two different endemic areas in Brazil.

PMID- 7732269
TI  - Prevalence of rubella antibodies in a non-immunized urban population, Sao Paulo,
      Brazil. The Division of Immunization, CVE.
AB  - The prevalence of rubella antibodies was evaluated through a random
      seroepidemiological survey in 1400 blood samples of 2-14 year old children and in
      329 samples of umbilical cord serum. Rubella IgG antibodies were detected by
      ELISA, and the sera were collected in 1987, five years before the mass
      vaccination campaign with measles-mumps-rubella vaccine carried out in the city
      of Sao Paulo in 1992. A significant increase in prevalence of rubella infection
      was observed after 6 years of age, and 77% of the individuals aged from 15 to 19
      years had detectable rubella antibodies. However, the seroprevalence rose to
      90.5% (171/189) in cord serum samples from children whose mothers were 20 to 29
      years old, and reached 95.6% in newborns of mothers who were 30 to 34 years old,
      indicating that a large number of women are infected during childbearing years.
      This study confirms that rubella infection represents an important Public Health
      problem in Sao Paulo city. The data on the seroprevalence of rubella antibodies
      before the mass vaccination campaign reflects the baseline immunological status
      of this population before any intervention and should be used to design an
      adequate vaccination strategy and to assess the seroepidemiological impact of
      this intervention.

PMID- 7732270
TI  - Absence of natural infection by Schistosoma mansoni in wild rodents captured in
      endemic areas for schistosomiasis in the State of Alagoas, Brazil.

PMID- 7732271
TI  - First case of human infection by trichophyton vanbreuseghemii in Brazil.

PMID- 7732272
TI  - [Auricular chromoblastomycosis. A case report].
AB  - It is presented a case of auricular chromoblastomycosis mimicking an eczematous
      lesions. The authors refer the rarity of this localization. All reported cases of
      auricular chromoblastomycosis have been caused by Fonsecaea pedrosoi but in the
      present case the etiologic agent was Phialophora verrucosa.

PMID- 7732273
TI  - [Visceral leishmaniasis and acquired immunodeficiency syndrome (AIDS). Report of
      a case].
AB  - This is a case report that describe an association of AIDS, visceral
      leishmaniasis and probable disseminated tuberculosis. Due to the spread of AIDS
      in developing areas worldwide this association would be more frequently, seen on
      subjects from endemic areas where this protozoonosis is prevalent. More than one
      opportunistic infection related with the endemic diseases of the developing
      regions can be associated with those immunocompromised patients.

PMID- 7732274
TI  - Fluorosis in a wild cotton rat (Sigmodon hispidus) population inhabiting a
      petrochemical waste site.
AB  - We have developed an in situ mammalian model for evaluating environmental
      contamination using wild cotton rats. In a series of experiments, 200 male cotton
      rats were captured during 4 collection periods (spring 1991 = 35; fall 1991 = 60;
      spring 1992 = 53; fall 1992 = 52). A total of 103 of these cotton rats were
      captured from control sites, and the remaining 97 were captured from an abandoned
      oil refinery. All sites were located in the vicinity of Cyril, Oklahoma. There
      were alterations in the incisors of cotton rats captured from the refinery site.
      Normal color of cotton rat incisors is deep yellow-orange, which is imparted by a
      pigment normally produced by ameloblasts. Grossly, the upper incisors of 37 of 97
      rats and lower incisors of 54 of 97 rats were affected. The affected incisors
      were white, chalky, and thin with striations and erosions of the enamel.
      Microscopic examination revealed that there were dysplastic and necrotic changes
      in the ameloblasts. The bone fluoride levels were significantly higher in rats
      captured from the refinery as compared to the rats captured from the control
      sites.

PMID- 7732275
TI  - Influences of dietary deoxycholic acid on progression of hepatocellular neoplasms
      and expression of glutathione S-transferases in rats.
AB  - Serial magnetic resonance imaging (MRI) was used to evaluate the influences of
      dietary deoxycholic acid (DCA) on the rate of progression of chemically induced
      hepatocellular neoplasms in rats. Male Fischer-344 rats with established
      persistent hepatocellular nodules generated by the Solt-Farber protocol were
      exposed to dietary DCA (0.3%) between 6 and 12 mo of age. Growth of nodules and
      carcinomas in vivo was measured by morphometric quantification of tumor images
      obtained every 6 wk. The final stages of neoplastic progression were determined
      by terminal histopathological examination and by expression and functional
      evaluation of glutathione S-transferase (GST) isoenzyme phenotypes. Dietary DCA
      increased the number of hepatocellular neoplasms per rat, accelerated the rate of
      growth of persistent nodules, and increased the histological progression of liver
      tumors. Expression of immunoreactive GST subunits Yf, Ya, and Yb1 was induced in
      early persistent nodules, a pattern that was maintained throughout the study in
      both basal diet and DCA-fed groups. However, 5% of early nodules and about 75% of
      advanced neoplasms were partially or completely deficient in GST Yb2 expression
      in both groups. DCA did not alter the cytosolic activity for the GST substrates 1
      chloro-2,4-dinitrobenzene (CDNB) or trans-4-phenyl-3-buten-2-one (tPBO) in tumors
      or surrounding liver. However, in both groups, CDNB activity was increased in the
      tumors relative to the surrounding nonneoplastic tissue, whereas activity for
      tPBO, a substrate more specific for the Yb2 subunit, was reduced in the tumors.
      All advanced neoplasms were similarly more resistant than surrounding liver to
      DNA-binding metabolites of aflatoxin B1 or benzo[a]pyrene. These data demonstrate
      that DCA can increase the progression of established hepatocellular nodules to
      larger, more advanced neoplasms but does not preferentially select for a specific
      GST phenotype. Preferential loss of constitutively expressed GST Yb2 in both
      basal diet and DCA-fed groups may be an important aspect of progression from
      resistant nodules to advanced cancers in this model. These studies also
      demonstrate that serial MRI is a useful tool for measuring the rates of
      enlargement and patterns of growth in established hepatocellular neoplasms.

PMID- 7732276
TI  - Constipation and megacolon in rats related to treatment with oxodipine, a calcium
      antagonist.
AB  - The constipatory effects of oxodipine, a dihyrdopyridine-type calcium antagonist,
      have been described in a 3-mo, 12-mo, and 30-mo feeding toxicity study in rats.
      This paper reports the occurrence of megacolon in rats as a result of the
      constipatory effects of chronic administration of oxodipine. The first mortality
      due to oxodipine was seen after about 1 yr of treatment at a dose of 225
      mg/kg/day. The toxic effects noted were dose-, time-, and sex-related. Female
      rats appeared more sensitive to the constipatory effects of the drug. The dose at
      which the effect occurred in both male and female rats was from about 75 to 675
      times the recommended therapeutic dose for humans. To the best knowledge of the
      authors, this is the first report of a calcium channel blocker causing
      constipation in rats.

PMID- 7732277
TI  - Characterization of a renal epithelial cell model of apoptosis using okadaic acid
      and the NRK-52E cell line.
AB  - Apoptotic cell death plays an important role in the pathogenesis of renal tubular
      epithelial damage and repair following tubular injury. Presently, the cellular
      factors involved in regulating apoptotic pathways in the kidney are unknown. To
      address the possibility that protein phosphorylation may regulate apoptosis in
      kidney cells, okadaic acid (OKA), a specific inhibitor of protein phosphatases 1A
      and 2A, was tested for its morphologic and biochemical effects on normal rat
      kidney epithelial cells (NRK-52E) in culture. As revealed by the DNA-specific
      stain DAPI, nuclei of cells treated with 1.0 microM okadaic acid contained
      irregular clumps of dense chromatin. Additional morphologic alterations typical
      of apoptosis were apparent within 2 hr after treatment with 1.0 microM OKA,
      including marked cellular rounding, cytoplasmic condensation, and cytoplasmic
      blebs. Ultrastructurally, 1.0 microM OKA caused cytoplasmic bleb formation,
      cellular fragmentation, condensation of heterochromatin into clumps, and
      segregation of nucleoli. At this stage, the cytoplasmic fragments and blebs
      contained many normal mitochondria. The attached, rounded cells also effectively
      excluded propidium iodide, demonstrating maintenance of membrane integrity
      despite pronounced morphologic alterations. A 2-fold increase in intracellular
      free Ca2+ was apparent 90 min after treatment with 1.0 microM okadaic acid.
      Transverse alternating field electrophoresis revealed the appearance of large DNA
      fragments of approximately 300-kbp. The appearance of these 300-kbp fragments
      correlated temporally with the observed elevation in intracellular calcium and
      the onset of morphologic alterations. However, preloading cells with EGTA-AM, an
      intracellular calcium chelator, obliterated the calcium elevation and had no
      effect on OKA-induced morphology, DNA fragmentation, or cell death. Detectable
      internucleosomal fragmentation occurred much later than the onset of morphologic
      changes (24-hr treatment time) and did not correlate with elevations in cellular
      calcium. These studies support the hypothesis that during apoptosis, chromatin
      condensation reflects chromatin cleavage at nuclease-sensitive sites between
      hexameric rosettes. These results also suggest that morphologic and nuclear
      alterations in the pathway of OKA-induced apoptosis occur independent of observed
      increases in intracellular calcium.

PMID- 7732278
TI  - The morphology of juxtaglomerular cell hyperplasia and hypertrophy in
      normotensive rats and monkeys given an angiotensin II receptor antagonist.
AB  - L-694,492 (DUP 532), an angiotensin II (AII) receptor antagonist, was given
      orally at 125 mg/kh/day to rats and monkeys for up to 6 mo to assess the effects
      of the compound on juxtaglomerular (JG) cells. In rats, mild JG cell
      hypertrophy/hyperplasia occurred and was associated with a 12-fold increase in
      the bromodeoxyuridine-labeling index of JG cells and a 10-fold increase in renal
      renin content. Ultrastructurally, intermediate cells with characteristics of both
      smooth muscle cells and granulated renin-producing cells as well as hypertrophied
      renin-synthesizing cells were seen in the afferent arterioles. In monkeys, marked
      hypertrophy and hyperplasia were seen with an 80% increase in JG cell numbers,
      mitotic activity, and a greatly increased renin content compared to controls.
      Three mo after drug withdrawal, an increased number of cells remained, which
      showed features of smooth muscle cells with essentially no renin. These results
      show that AII receptor antagonism stimulates increased renal renin production by
      hypertrophy of existing granulated cells, metaplasia of smooth muscle cells to
      renin-synthesizing cells, and cell proliferation. When treatment was
      discontinued, the renin-producing cells redeveloped the features of smooth muscle
      cells, but, as we have shown with enalapril (augioteusin-converting enzyme
      inhibitor), the increase in their number persists for at least 3 mo.

PMID- 7732279
TI  - Sequential functional and morphological alterations during hepatocarcinogenesis
      induced in rats by feeding of a low dose of 2-acetylaminofluorene.
AB  - The early cellular events in liver carcinogenesis were studied in Fischer-344
      male rats that either were fed 200 ppm 2-acetylaminofluorene (AAF) for up to 10
      wk or were fed the carcinogen for 8 wk followed by maintenance for an additional
      24 wk. By 1 wk of exposure, AAF caused a reduction in the number of glutamine
      synthetase (GS)-positive centrilobular hepatocytes, an increase in DNA
      synthesizing hepatocytes in the central areas of the hepatic lobules, and a shift
      from multinucleated to mononucleated hepatocytes, although overt hepatocellular
      necrosis was not evident. By 3 wk, altered hepatocellular foci characterized by
      deficiencies in iron storage (IS-) and collagen production and by expression of
      gamma-glutamyl transferase (GGT+) and placental-type glutathione transferase
      (PGT+) activity appeared. Single PGT+ cells were also found. During continued
      exposure, foci increased in number, size, and total area with the increases
      escalating between 8 and 10 wk of exposure. Cessation of AAF exposure at 8 wk
      resulted in a slight decrease in the number of foci after a further 6 wk of
      maintenance, but with continued maintenance for another 6 and 12 wk, the number
      again increased. IS- characterized the majority of foci during carcinogen
      administration, whereas after cessation of exposure, GGT+ and PGT+ foci
      predominated. None of the foci were positive for GS. After AAF exposure for 10
      wk, a few neoplasms developed and greater numbers occurred after maintenance for
      a further 24 wk of rats exposed for 8 wk. We conclude the following: (a) the low
      dose of AAF caused subtle alterations in function and proliferation of normal
      hepatocytes and converted hepatocytes into focus cells; (b) reduction of the GS+
      area is a sensitive indicator of cytotoxicity of AAF; (c) the development of some
      foci at an early stage depends on a promoting action of AAF, which ceased when
      the carcinogen was withdrawn, allowing some foci to undergo reversion; (d) a
      strong linkage exists in expression of IS-, GGT+, and PGT+ in foci; (e) the
      carcinogenic process accelerates in the absence of any indication of increased
      cytotoxicity by AAF; and (f) under the conditions of this study, no GS+ foci,
      adenomas, and carcinomas were found, indicating that no carcinogen-induced
      expression of GS occurred in these lesions and that GS expression is not linked
      to other phenotypic abnormalities.

PMID- 7732280
TI  - Automated and semiautomated analysis of rat alkaline phosphatase isoenzymes.
AB  - A semiautomated quantitative assay for rat serum alkaline phosphatase (ALP)
      isoenzyme determination was developed, incorporating selective precipitation of
      bone alkaline phosphatase (BALP) with wheat germ lectin and differential
      inhibition with levamisole for determination of intestinal alkaline phosphatase
      (IALP). The assays for each isoenzyme were linear over a broad range of
      activities. The within-run and between-run coefficients of variation were less
      than 11% for all 3 isoenzymes. Dilution of serum with saline results in an
      artifactual overestimation of BALP activity. Comparison of ALP and ALP isoenzyme
      activity in rats of various ages showed that BALP activity drops dramatically
      with increasing age of rats. IALP activity is greater in immature rats compared
      to that in mature rats. While there was no difference between male and female
      rats at 4 wk of age with regard to total ALP activity and activity of any of the
      isoenzymes, total ALP activity and activity of the individual isoenzymes were
      higher in males than in females at most ages over 4 wk. Gavage with corn oil
      resulted in increased serum IALP activity, and bile duct ligation resulted in
      increased liver alkaline phosphatase activity. This combined assay for the 3 ALP
      isoenzymes in rat serum is an efficient means of analysis of large numbers of
      samples and should increase markedly the specificity of serum ALP activity in
      identifying the target organ in toxicologic studies when serum ALP activity is
      increased.

PMID- 7732281
TI  - XIII International Symposium of the Society of Toxicologic Pathologists. The role
      of drug metabolism and pharmacokinetics in toxicologic pathology. Charleston,
      South Carolina, June 5-9, 1994. Abstracts.

PMID- 7732282
TI  - The 9th Aspen Cancer Conference Workshop. Mechanisms of toxicity and
      carcinogenesis. Aspen, Colorado, July 16-19, 1994. Abstracts.

PMID- 7732283
TI  - [Possibilities of food frying in relation to the diet/degenerative diseases].

PMID- 7732284
TI  - [Do they have to fluoridate water for public usage?].
AB  - In order to facilitate the convenience of fluorating or not the public use
      waters, a bibliographic review about the positive or negative aspects of this
      public health measure has been made. The different epidemiologic surveys about
      dental health conditions in our country, since 1969 till the present time, have
      been reviewed. From the analysis of these works, it can be deduced that the
      degree of caries severity index (DMF) is situated at a moderate to low level,
      according to the classification of the World Health Organization. The advantages,
      inconvenience, cost and percentage of caries reduction of the different methods
      to prevent dental caries are studied. It is considered positive to go on with the
      policy of public use waters fluoration, provided that is is based on a series of
      prerequisites which guarantee the highest level of effectiveness and efficiency.
      Among the different objective criteria to fluorate waters, the following ones
      stand out: a high prevalence of caries, a good system of waters out: a high
      prevalence of caries, a good system of waters diffusion, a natural fluor
      concentration lower than 0.7 grams/litre, the cost-benefit analysis, the
      population size. The elaboration of studies to determine the total quantity of
      fluorides, ingested by the population from various sources, is recommended.

PMID- 7732285
TI  - [Prevalence of Hepatitis B serologic markers among the personnel of the
      institution for children with deficiencies].
AB  - BACKGROUND: The risk of infection by the hepatitis B virus (HBV) in institutions
      for children with deficiencies has been established in several studies. The
      purpose of this work was to know the prevalence of HBV markers, among the
      employees in an institution of that kind, and its association with several risk
      factors. METHODS: A transveral epidemiologic survey has been carried out to
      determine the markers prevalence of infection by hepatitis B virus (HBV) and its
      association with certain risk factors, among the 200 workers of an institution
      for children with deficiencies. Determinations, by radioimmunoassay were: HBs Ag,
      anti-HBs and anti HBe. RESULTS: The participation was 95%, with a prevalence of
      any marker of 7.9% (IC95 + 4.1-11.7). No HBs Ag carriers were detected, taking
      occupation as an indicator variable with three categories: Trades and auxiliary
      health personnel versus teachers, the logistic regression analysis showed odds
      ratios, adjusted for age, sex and working time, for trades and auxiliary health
      personnel, respectively. CONCLUSIONS: Vaccination is the preventive
      recommendation for HBV in these institutions, because of the difficulty to find
      other factors associated to HBV. The possibility of introducing a universal
      vaccination is controversial.

PMID- 7732286
TI  - [Social attitude towards health participation].
AB  - BACKGROUND: The community health participation is an important issue for all
      health systems based on a Primary Health Care, which emphasizes prevention and
      promotion, as a complement to assistance. In this survey, the social attitude
      towards health participation is studied, taking into account the different
      research paradigms on Social Sciences, the models of health behaviours, the
      meaning of participation and the meaning of the own attitudes. METHODS: A Likert
      scale of 18 items, which constitutes a part of a general health survey of 128
      variables, is elaborated and validated. It is complemented with a personal
      interview to 1371 persons in a random sample from four health areas. RESULTS: The
      data obtained show that there are neither statistical significant differences
      among areas in relation with having or not a Health Council, nor between men and
      women. The attitudes towards participation are more favourable among young
      people, bachelors and persons from a high socioeconomic status, hig degree
      studies, white collar professions, and the persons going to the doctor with the
      lowest frequency, show a positive tendency. The factorial analysis identifies
      three dimensions: a) Self-care, b) political and c) community health agent. The
      discriminant analysis shows that variables (age, civil, status, socioeconomic
      level, studies...) classify correctly 74% of cases. CONCLUSIONS: The personal
      profile, showing a health participative attitude, is consistent, in most
      variables, with that published by previous reports.

PMID- 7732287
TI  - [Cervical cancer of the uterus. Analytic epidemiology].
AB  - BACKGROUND: Malignant tumour in cervix is an important cause of death in young
      women. Through community programmes of detection and early diagnosis, a
      significant reduction in the incidence of invading forms and mortality due to
      this cause has been achieved. Knowing the Prevalence of premalignant lesions and
      cancer in the sexually active women population, establishing the frequency of
      risk to different factors and associated risk to these ones in this population,
      constitutes a part of this study objectives. METHODS: A transversal study is
      carried out, with a sample of population older than 20 years or younger, but
      sexually active, constituted by 4262 women, selected at random from a population
      of 7222 persons cared in family planning centers and distributed in 15
      localities. In every case, the colposcopy has been made in a systematic way,
      associated to the cytology with a biopsy of every atypical image. Among the risk
      factors studied, the expositions to Rx, sexual promiscuity, genital infections,
      mycosis and infertility are included. The existence, as a clinical discovery, of
      a suspected lesion or an atypical colposcopy are includes as risk markers. The
      test of, the calculation of Odds Ratio, and 95% confidence interval, the
      etiological fractions, the multivariant analysis and the calculation of OR,
      adjusted to qualitative variables and the comparison of means for quantitative
      variables, are used in the analysis. The programme SAS is used as a software.
      RESULTS: The prevalence of cancer found was 0.938 per one thousand women and the
      frequency of precursory lesions was 38.2 per one thousand. The comparative study
      with regard to different variables between women with benign deteriorations or
      normality and women presenting a diagnosis of premalignant lesions or carcinoma,
      proves that, without existing differences in relation to age, beginning of sexual
      relations ans number of pregnancies, the risk of suffering from cervix cancer
      increases with sexual promiscuity, exposition to Rx, genital infections, mycosis
      and infertility. CONCLUSIONS: On the basis of the prevalence detected, it is
      considered necessary keep and to increase the coverage of actions of cervix
      cancer prevention in women, increasing the participation of the whole of sexually
      active women in the programmes. The presence of risk factor would modify the
      number and periodicity of gynecological controls.

PMID- 7732288
TI  - [Tubercular infection and its trend among school children in the population of
      the Barcelona suburbs].
AB  - BACKGROUND: Tuberculosis infection is a suitable method to evaluate a community
      tuberculosis endemic. The calculation of infection indexes (incidence,
      prevalence, year risk and their decline) have been used to analyze this endemic
      and ist tendency during 22 years in a suburbial city. METHODS: Practice of the
      tuberculin test (Mantowx) to almost the totality of schoolchildren during the
      academic years. 1968-69, 1980-81 and 1981-82; and 1989-90 and 1990-91 as well.
      During the years 1981-82 and 1990-91, the test was repeated in a sample of
      schoolchildren to detect the reaction converters (incidence of infection).
      RESULTS: The prevalence of tuberculosis infection is very high (7.5% in the first
      primary school year and 15.2% in the 8th primary school year during 1968-69, and
      decreases to 5.1% and 11.7% during 1980-82 was 2.6% and 1.5% in 1989-91. The
      decline of the infection risk is very low: about 6% during the whole period, and
      it is higher: 9%, in its second part. CONCLUSIONS: The high tuberculosis can be
      related to the population social deficiencies. The favourable tendency observed,
      during the last ten years, can be attributed to an improvement in the health care
      and, specifically, in the treatment of patients of tuberculosis.

PMID- 7732290
TI  - [Jargon, culture and information].

PMID- 7732289
TI  - [The application of the diagnostic indicator during hospital admission].

PMID- 7732291
TI  - [A Consensus Conference: clinical indications and risks of fresh frozen plasma].

PMID- 7732292
TI  - [Leishmaniasis in peninsular Spain. A historical-bibliographic review (1912
      1985)].
AB  - A bibliographic-historical review of leishmaniasis in Spain during the period
      1912-1985 is carried out. The bibliographical prospecting has allowed to collect
      a total of 402 works; out of them only 79 are included in this review. From
      reading them, it can be deduced that, starting from its discovery in the coast of
      Levante in 1912, leishmaniasis has been a very well known disease in Spain,
      during the first third of our century, period in which a remarkable prevalence
      took place, as it follows from the works published basically by Pittaluga and
      colleagues. In them, plentiful clinical and epidemiologic data are collected,
      many of them having laid the foundations of this disease knowledge in our
      country. Nevertheless, the extrapolation of data from other geographical regions
      introduced confusions, which have continued till recent time, basically on what
      refers to the existing relation between the aetiological agent and the clinical
      case. On the other hand, nowadays, current important matters such as the part of
      person's immune response in the appearance of a visceral or cutaneous case of
      leishmaniasis, independently from the parasites specific identity or the presence
      of asymptomatic leishmaniasis, are already found in pioneer works. In the course
      of the work, a review is made of the information, obtained form the Spanish
      bibliography, on the leishmaniasis aetiological agent in Spain, the vector and
      the host as well as the various clinical cases of human and canine leishmaniasis,
      their epidemiology, diagnostic and treatment.

PMID- 7732293
TI  - [Study of the prevalence of hypercholesterolemia in Extremadura].
AB  - BACKGROUND: Cardiovascular diseases appear as the first cause of mortality in the
      Autonomous Community of Extremadura, which represents 48% of all deaths. The
      rates of hospital morbidity situated them as the 3rd cause of hospital
      admissions. Because of its part in the production of atherosclerosis and its
      associations with ischaemic heart disease, the hypercholesterolemia is one of the
      necessary factors to be controlled in populations, in order to reduce mortality
      by coronary disease. Therefore, it becomes necessary to know the magnitude and
      prevalence of serum cholesterol and lipoproteins in our community, for there
      exist no published data on the matter and as a previous step to the introduction
      of intervention programmes. METHODS: An observational transversal study,
      stratified by blood pressure and municipalities, in a population of 30 years or
      more, is carried out. The size of the sample is 1060 persons; out of them 548
      persons are hypertensive and 512 normotensive; these are taken as control group.
      In this populations, analytic tests are made to know the total cholesterol, HDL
      cholesterol, LDL-cholesterol and Triglyceride levels. The TEST, the Odds Ratio
      Calculation, the means comparison (Student T) and means estimation are used in
      the analysis. RESULTS: Out of the total sample, 44. 18% show equal or higher than
      240 mg/dl cholesterol levels and 53. 96% show higher than 150 mg/dl LDL-C levels;
      plasmatic triglyceride concentrations higher than 200 mg/dl appear in 10% of the
      sample. The estimated cholesterol average in the population of Extremadura, older
      than 30 years, is 202.9 : 252 in normotensive men and 230. 68: 241.1 in
      hypertensive men. In women, intervals are 230. 5:241:8, and 231.7 [corrected]
      248.5 respectively. The association of hypertension with hypercholesterolemia
      converges in 46.17%, and frequency in normotensive persons is 43.36%; These
      differences are almost significant. The indicated coexistence represents an
      important increase of coronary risk. With regard to age, it is directly
      associated to cholesterolemia and LDL-C values with an Or of 2.47 and 2.41
      respectively. On the contrary. Triglyceridemia acts as an independent variable,
      when studying its relation with age. For sex variable, a statistically
      significant association with Triglyceride concentration is proved: These
      concentrations are higher in women with ar Or of 2.64. With regard to cholesterol
      levels, there exists a predominance in men of less than 45 years, which is
      surpassed by women in the age group of 45-60 and becomes equal in normotensive
      populations after this age. No correlation is found between the pathologic
      antecedents of cardio/cerebrovascular disease and plasmatic cholesterol levels.
      CONCLUSIONS: The authors opinion is that these important figures in the
      Autonomous Community, must compel, on the one hand, to study in further depth the
      main outside or environmental risk factors which have an influence on
      cholesterolemia an low density lipoproteins levels in the Community of
      Extremadura and, on the other hand, they must compel to control
      hypercholesterolemia as well as other risk factors, which contribute negatively
      to morbid-mortality of cardiovascular diseases.

PMID- 7732294
TI  - [Thoracic radiography in occupational health examination of hospital personnel.
      Making decisions].
AB  - BACKGROUND: The routine chest radiography has been legally suppressed because of
      its low diagnostic profitability in non selected populations. Health surveillance
      of occupational populations at respiratory risk is entering a transitional
      period, where new guidelines are needed. Therefore, we determined to study the
      percentage of pathological findings in the chest radiographies of health
      examinations for hospital workers and whether it was possible to obtain
      explicative models allowing to calculate the probability of radiographies
      alteration. METHODS: A representative stratified sample of workers belonging to
      the Hospital La Paz in Madrid is studied, elaborating a transversal study based
      on the first health examination of their clinical history and two chest
      radiographies of further examinations. We carried out a multivariant analysis to
      calculate the probability of their alteration. RESULTS: We obtain alterations
      percentages of 19% for the first chest radiography; 23.5%, 22% and 21% for the
      two further ones and for the total, respectively. The explicative models obtained
      are based on age, family and personal antecedents of the respiratory disease,
      number of cigarettes smoked, cholesterol levels, the Mantoux test and the
      previous radiographies alteration. CONCLUSIONS: These equations may be an
      additional instrument together with labour environment considerations and within
      a clinical context, to help to the health specific occasional surveillance of the
      respiratory risk of hospital personnel.

PMID- 7732295
TI  - [Educational and health dimensions of health education at school: a participative
      total experience in 2 health regions of Murcia].
AB  - BACKGROUND: The results of and experience on School Health Education during two
      years and in two health areas, which intends to promote solid contacts between
      all people interested in carrying out activities included in daily work, and,
      this way, to improve the schoolchildren habits are shown. METHODS: The activity
      is situated in the Investigation Action paradigm. Quantitative and qualitative
      methods are used in the process and product evaluation. RESULTS: The programme
      has had an statistically significant effect on the habits considered to be of
      interest (dental hygiene and physical exercise) and no effects on those habits on
      which no work was done. There have been 13 Educational Centers, 2 Health Centers
      and the Faculty of Medicine Sociosanitary Sciences Department. Collaboration,
      among all interested people, has been increasing, although there have been found
      difficulties and giving up. CONCLUSIONS: Our opinion is that the role to be
      played by the Health Councils and the School Councils is essential to develop the
      recent ministerial dispositions on the matter, within the scope of health areas.

PMID- 7732296
TI  - [Progress in surveillance of acute respiratory infections in the Republic of
      Cuba].
AB  - BACKGROUND: A process of techniques perfection of the epidemiologic surveillance
      of morbidity by Acute Respiratory Infections, with the purpose of obtaining a
      better and more appropriate description of the problem, was carried out. METHODS:
      A mathematical model of Fourier harmonic analysis and an Arima model was applied
      to the time series of weekly consulting rates for those diseases by age groups
      and provinces. This allowed to identify the epidemical moments, based on the
      prediction of expected values and an specific cut-off. RESULTS: The application
      of this technique made it possible and early and appropriate identification of an
      epidemical rise in children of less than 1 year, between July and August of 1988,
      with the identification of the Respiratory Syncytial Virus, as the aetiological
      agent. In the age-group of 5-14 years, a rise was observed in September, at the
      beginning of the school-year, and a smaller one between May-June of 1989. In the
      group age of 65 years and more, an epidemical increase took place from July to
      October. CONCLUSIONS: The use of these techniques provided new possibilities to
      make more precise and appropriate recommendations to improve epidemiological
      surveillance of these diseases at a national level.

PMID- 7732297
TI  - [Judicial claims for medical malpractice].
AB  - BACKGROUND: Physicians' legal liability regarding malpractice has reached a
      previously unknown importance in Spain. This paper brings forward some
      statistical data on judicial claims presented by patients and their relatives.
      METHODS: The whole of resolutions of the First and Second Court of the Supreme
      Court were collected between 1870 and 1992. In Madrid, the number of lawsuits in
      proceedings were obtained from a sample of the Courts at the Plaza de Castilla in
      April 1990, and figures on legal complaints, accusations and demands were
      obtained through consultations at the Medical College. RESULTS: The great
      majority of verdicts, both in Civil and Penal Jurisprudence, correspond to the
      last 13 years. In Madrid, the average of penal cases in proceedings was 3.8 per
      Court, and an appreciable increase of claims can be noticed, with an annual rate
      of about 0.4 per 100 physicians. CONCLUSIONS: Appealing to Justice in order to
      accuse a practitioner for presumed malpractice is no longer an unusual event.
      Various reasons contribute in this respect. However, other reasons exist to
      consider the Spanish situation very far from the level in the United States of
      America.

PMID- 7732298
TI  - [Rational use of drugs].

PMID- 7732299
TI  - [The role of public health reviews].

PMID- 7732300
TI  - [The personnel of the National Health System. A reflection on evolution, current
      status and future perspectives].

PMID- 7732301
TI  - [Smoking cessation programs at the worksite: the need for its implementation in
      Spain].
AB  - Tobacco smoking is the most important health problem in Spain, as in the rest of
      the developed countries; been also recognized as the most preventable cause of
      premature morbidity and mortality in the western world. Interventions to reduce
      tobacco consumption in Spain, has been mainly addressed by means of physician
      patient interaction, lacking the approach for community and workplace
      interventions. This article emphasize the need for the implementation of
      strategies of smoking cessation programs in the worksite, encouraging to health
      professionals to design, to apply and to evaluate these interventions. The most
      often used approaches to reduce tobacco smoking at the worksite are considered,
      addressing cost-effectiveness issues related with the characteristics of the
      Spanish Health System.

PMID- 7732302
TI  - [Drug consumption and arterial hypertension in a rural population].
AB  - BACKGROUND: The incidence of arterial hypertension and other cardiovascular
      diseases has undergone an increase in Spain during recent years, particularly in
      rural areas, as a consequence of progressive population aging. A study is made of
      drug prescriptions associated with non-complicated arterial hypertension in a
      rural setting. METHODS: Field work was initiated in four rural municipalities of
      Castellon province on the Spanish Mediterranean coast, with highly aged
      populations. Out of a total population of 1064, 60% made use of the area health
      care services in the course of year. Of these, 11% had at one time or other
      suffered one or more episodes of non-complicated arterial hypertension. RESULTS:
      The drugs most commonly prescribed were calcium antagonists, angiotensin
      converting enzyme inhibitors, and diuretics, although differences in order of
      importance were seen depending on patients age. The cost of the active components
      prescribed were below the average of those commercialized within each therapeutic
      group. CONCLUSIONS: To conclude, interactions were detected with other drugs used
      by the patients while on hypotensives. The most relevant in this sense were
      nonsteroidal anti-inflammatory agents; consumption of these drug was very high,
      in part also due to the high incidence of osteomuscular complaints among the
      geriatric population of the zone.

PMID- 7732303
TI  - [Assessment of the nutritional status of school children in Cadiz].
AB  - BACKGROUND: Nutritional conditions of a population constitute an important health
      indicator. Children and adolescents are considered to be at high risk of
      suffering excess of defect nutritional problems; however, preventive action is
      easier in this group. For this reason, we decided to carry out a valuation of
      nutritional status in a school children population of a marginal area in Cadiz
      Province. METHODS: Students, registered in the second level of Primary School of
      the only public school in the area, were studied. They were directly examined on
      their nutritional condition by clinical, anthropometrical and biochemical study.
      In the same way, a valuation of the population socio-economical status was
      carried out, according to GRAFFAR criteria. The information obtained was
      tabulated and analyzed using the computerized programme EPINFO. Results were
      compared with the OMS Standard International and with the Ruiz's study, carried
      out in the same province. RESULTS: Both: body weigh/age and Quetelex indexes
      shown lower values than the standard and than Ruiz's study, specially in the
      groups of higher age (except for boys of 15 years old). This was also shown for
      the arm perimeter. Nevertheless, in the tricipital skin fold, values were higher
      than the standard in the ages of 12 and 13 years; but lower than the Ruiz ones in
      some ages. CONCLUSIONS: The results obtained might suggest the existence of an
      unbalanced and/or poor diet among school children; this fact could be verified
      carrying out a complete dietetic assessment of this collective.

PMID- 7732304
TI  - [Seroepidemiological study and program of vaccination against hepatitis B in
      school children in Extremadura].
AB  - BACKGROUND: The control of Hepatitis B as a community health problem which
      implies the reduction of the number of cases and carriers cannot be achieved
      merely through selective vaccination of high risk groups and immunization of
      newborns whose mothers are carriers. The decision to introduce universal
      vaccination on a constant basis should be based on the epidemiological
      characteristics of the infection in the community, among other reasons. METHODS:
      Along these lines, a study of seroprevalence of the infection was carried through
      a random sampling of ages groups taken from a population with no history of
      hepatitis and low risk groups, using a survey of 855 people and a retrospective
      study of seroprevalence in different high risk groups with a survey of 2,183
      people. RESULTS: The prevalence of infection estimated at intervals in the
      general population not included in high risk groups is 8.05-12.07, and that of
      carriers of HBs Ag 0.07-1.09. The risk of infection increases significantly after
      14 years of age (p < 0.001) with an OR of 25.22. Sexual transmission as a means
      of spreading the virus among the general public is demonstrated by the data
      obtained from sexual promiscuous People and prostitution: 58.53% and 44.21%
      respectively. CONCLUSIONS: We consider it necessary to employ universal
      vaccination of adolescents within the children's immunization programmes, at a
      recommended age of 13 before finishing primary school and abandoning school,
      while still keeping the prophylactic measures and immunization of high risk
      groups. This will also allow us to simultaneously prevent infection by Hepatitis
      Delta in the Autonomous Community both as a co-infection by HBV and an
      overinfection. In this programme we advocate the elimination of serological
      studies on Hepatitis B (due to cost-efficiency studies) and are in favour of
      periodic future research on seroPrevalence.

PMID- 7732305
TI  - [Hydatidosis control in the province of Rio Negro, Argentina: development of
      primary care programs].
AB  - Hydatidosis is a serious Public Health problem in the Province of Rio Negro,
      Argentina. This situation has promoted the implementation of a control programme
      based on the canine systematic deparasitation with Praziquantel, health
      education, work control and care of persons. The accumulated experience of 15
      years works, carried out to develop the last work--line mentioned above, is
      presented in this study. The activities includes the registry of human cases, the
      early identification of asymptomatic carries, the infected persons derivation to
      the hospital system in order to allow their appropriate treatment, the
      longitudinal follow up of the operated cases and the epidemiologic surveillance
      of the human hydatidosis situation. A network of laboratories was organized, as a
      support to satisfy the hospital demand, under the coordination of a central
      laboratory of reference and serologic surveys, among the groups at risk, were
      also carried out. The information registered indicates that a total of 60,078
      serologic tests were carried out in the whole Province: out of them, 22,899
      corresponded to hospital demand (DD5) and 37,179 to serologic surveys (originally
      latex, then DD5, and now Elisa). 65% of the cases, diagnosed by official
      register, is derived from rural areas to complexity hospitals, to be put under
      surgical treatment, and, out of these operated persons, only 3.9% is derived from
      the appearance of clinical symptomatology. A sustained reduction in the average
      days of stay, in lethality and in the rate of serologic prevalence in school
      children from 7 to 13 years of age, are achieved.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7732306
TI  - [Evaluation of the quality of the treatment indicator of the State Information
      System on Drug Addiction].
AB  - BACKGROUND: In Spain, the problems caused by cocaine and opiates consumption are
      monitored through the State Information System on Drug Abuse (SEIT); one of its
      indicators is the number of admissions for ambulatory treatment for these drugs
      abuse/addiction (Treatment Indicator). METHODS: The information quality of this
      indicator was evaluated retrospectively during 1988 by comparing the data
      notified to SEIT with those registered in the treatment centres. For that, a
      random sample of cases among the clinical records from the notifying centres, and
      another among the cases registered in the SEIT Central Unit, were selected and
      crossed, calculating the precision and concordance indexes and observing the
      possible differences between both samples. In addition, mechanisms of
      notification and information organization were examined in the selected centres.
      RESULTS: In 1988, at state level, the sensibility was 81% and the predictive
      positive value 96%. As a whole, the SEIT underestimated the number of cases by
      16%. Although the sample was not representative by Autonomous Communities,
      important between-regions differences in precision were observed. No significant
      differences of the information quality were found in relation to the centre size
      (although quality was lower in small centres) nor between the "true cases"
      notified and those not notified. Disparities, among centres, in relation to
      mechanisms of notification and information organization were found. CONCLUSIONS:
      The SEIT is of a great value to know the characteristics of the persons treated
      for opiates or cocaine in Spain; but the between-regions variations on its
      precision might limit seriously geographic comparisons in the number of cases. It
      is necessary to evaluate periodically the indicator quality and to improve the
      consistency of data registration mechanisms.

PMID- 7732307
TI  - [Quality of the certification of death due to acute reaction to opiates and
      cocaine among inhabitants of the City of Madrid].
AB  - BACKGROUND: Deaths by acute reaction from drugs consumption (RAD) particularly
      heroine or cocaine, collected in routine morality statistics, have not changed
      substantially during the last ten years, whereas an specific collection system
      (State Information System on Drug-Abuse SISD) presented a great increase. For
      this reason, we try to measure the validity of drug-related deaths certificate.
      METHODS: The cause of death, corresponding to the persons, from 15 to 39 years of
      age, decreased in 1988 and residing in the Municipality of Madrid, registered in
      the Civil Register Decease Book and in the death Statistics Bulletins (DSB) was
      compared with the cause present in the autopsy report. RESULTS: A detection rate
      of 2.45% for the CR and 3.27% for the DSB were obtained. With the consequent
      correction, the RAD for this age group would be the second cause of mortality in
      the Municipality of Madrid and deaths related to circulatory and respiratory
      system would decrease in a great measure. CONCLUSIONS: It is necessary to improve
      substantially the collection of this cause of death in mortality statistics if we
      want a correct measurement of drug abuse lethal effects and the effectiveness of
      control programmes on this health problem.

PMID- 7732308
TI  - [Seroprevalence of human toxoplasmosis in Cordoba].

PMID- 7732309
TI  - [Public health].

PMID- 7732310
TI  - [An epidemiological study on cardiovascular risk factors in 35-64 years old
      Spanish population].
AB  - BACKGROUND: Cardiovascular disease (CVD), specifically Coronary Health Disease
      and Cerebrovascular Disease, are the first cause of death in Spain. Information
      about their main modifiable risk factors (RF) distribution is needed in order to
      CVD prevention. The purpose of this paper is to estimate these RF prevalence and
      distribution by age, sex and habitat groups, i.e. tobacco smoking,
      cholesterolemia, high blood pressure, and obesity in the Spanish population.
      METHODS: A random cluster sampling cross-sectional study, stratified by habitat
      (rural and urban), age and sex, was carried out on 2021 men and women of 35 to 64
      years of age in 1989. Definition criteria for variables studied were those from
      WHO and European Atherosclerosis Society. Additional data for study were
      treatment and control level of hypertensives, cardiovascular drugs consumption
      and CVD family history. RESULTS: Participation rate was 73.3%. Mean
      cholesterolemia was 211.2 mg/dl (210.1 mg/dl in males and 211.9 mg/dl in
      females). Mean systolic blood pressure was 132.3 mmHg (133.4 and 131.6 mmHg in
      men and women, respectively). Mean Quetelet Index was 27.5 kg/m2 (27.2 and 27.6
      for men and women). 49.4% of males and 16.7% of females were smokers (25.7% and
      78.3% were never smokers, respectively). Prevalence of hypercholesterolemia (> or
      = 250 mg/dl) was 18.6% in men and 17.6% in women, and that of high blood pressure
      (> or = 160/95 mmHg) was 21.5% in men (49.1% of them treated, and 26.7%
      controlled), and 19% in women (60.9% treated and 38% controlled). 18.4% of men
      and 27.4% of women had a Quetelet Index greater than thirty. 15 to 20% of
      individuals reported a CVD family history. For all these variables there were
      generally differences according to age, sex, and habitat. CONCLUSIONS: Risk
      factors distributions and prevalences in Spanish middle-aged individuals rank
      relatively high. This suggest need of further study and control of them to
      address CVD prevention properly.

PMID- 7732311
TI  - [An alternative model of health sciences in relation to women].
AB  - BACKGROUND: The purpose of this article is to present an alternative medical
      model to the hegemonic model, from the point of view of gender. Gender is
      believed as a socio-cultural construction defining men and women ways of behaving
      in society at a definite historical time. Gender consideration in epidemiologic
      analysis, together with other social variables, constitutes a new approach in the
      knowledge of women practices. Gender values are the basis to transform social
      relations and health care within the health system. The position I show includes
      a macrosocial level: the State and social politics, and a microsocial level:
      woman and her connection with the doctor in her daily life scope. METHODS: A
      content analysis of the compiled bibliography was carried out from the point of
      view of gender. A Primary Health Care Center belonging to a marginal district in
      the City of Buenos Aires, Argentine was taken as reference. RESULTS AND
      CONCLUSIONS: As result of this study, a woman care typology, emphasizing the
      differences between an hegemonic medical model and an alternative model, was
      elaborated. In the same way, concepts, which may be a guide in the construction
      of an alternative model to the hegemonic one, are handled.

PMID- 7732312
TI  - [Data envelopment analysis: its use to assess efficiency of hospital preventive
      medicine services of Andalusia].
AB  - BACKGROUND: The evaluation of hospital units efficiency is a major matter of
      health services management. Among the techniques to measure efficiency. The Data
      Envelopment Analysis (DEA) can be used in multiple resources units (inputs)
      obtaining multiple products (outputs). The objective of this study is the
      evaluation of Hospital Preventive Medicine Services in Andalucia, using the
      technique DEA. METHODS: The Preventive Medicine Services from seven hospitals of
      Andalucia were selected. DEA is technique, based on a linear programming, which
      finds the weights, which make a Service efficient in relation with the rest. The
      relative efficiency of seven units was calculated. The unit with the best
      practice was found by means of cross efficiency matrixes. With regard to the
      inefficient services, their necessity of increasing activities to achieve
      efficiency was identified. RESULTS: Two efficiency assumptions were elaborated.
      In the first one, 4 services were efficient (Efficiency = 1) in relation with the
      rest. In the second one, the Service S.1 was inefficient. Among the efficient
      units, S.2 shown the highest average efficiency in both assumptions and appeared
      as the reference unit for all the inefficient ones. CONCLUSIONS: In the
      evaluation of Preventive Medicine Services efficiency, at least, three of them
      shown some kind of inefficiency. The Service S.2 was the point of reference for
      inputs and outputs selected.

PMID- 7732313
TI  - [Lung cancer mortality trends in Asturias (1976-1989)].
AB  - BACKGROUND: The Trend of lung cancer mortality rates in Asturias during 14 years
      is studied in order to know whether it shows the same change pattern described
      for other countries. METHODS: With this purpose, a graphic study of adjusted and
      age specific rates, including and analysis of birth cohorts, is carried out, and
      the change average percentage per year and the sex ratio are calculated. RESULTS:
      In men, the continuous increase of mortality stands out (change average
      percentage per year of age adjusted rates of 4.83%) with the only exception of
      the age group of 45-54 years, which had a variation per year of 1.90%, whereas in
      women, an overall decrease (-1.18 %) was observed, with the exception of women
      older than 74 years, who showed an increase of 1.73% per year. In men, the
      cohorts analysis showed on increasing cohort effect in all generations and a
      decreasing effect in some women. CONCLUSIONS: Lung cancer will probably go on
      increasing in Asturias in the next years, among men, whereas in women, it seems
      that a generalized decrease has been initiated, mainly in the youngest ones and
      the, increase, observed in other countries in previous years, is not evident.
      Additional studies, focused on the reasons for these trends, will be necessary
      and basically the following up of the evolution in men of 45-54 years, whose
      incipient decrease may indicate a change of trend, which facilitates hypothesis
      generation and verification.

PMID- 7732314
TI  - [Periodontal disease in juvenile diabetics and non-diabetics].
AB  - BACKGROUND: Knowing the prevalence of periodontal disease, to identify some
      associated variables in youth population. Insulin dependent diabetes mellitus
      (DMID) has been included as a common variable. METHODS: Cross-sectional study
      over 383 individuals, 11 to 18 years old. Chi square and Odds ratio (95%
      confidence limits) have been determined. RESULTS: Periodontal disease prevalence
      is 37.53%. An epidemiological and statistical association were found with:
      Insulin-dependent diabetes mellitus, low social class, poor dental hygiene and
      plaque index over 0.20. CONCLUSIONS: Juvenile diabetic population must be
      considered as a high risk group for periodontal disease.

PMID- 7732315
TI  - [Morbidity in rural environment. A comparative study of 2 methods of obtaining
      data].
AB  - BACKGROUND: The great amount of information required to have the possibility of
      carrying out an opportune correct health planning has been the cause of an
      increased interest in the Information Systems about morbidity and it is primary
      level where the obtention of data becomes more difficult. The source of data is
      one of the problems to be solved; health surveys and consultation registers have
      been the most frequently used. Both show differences in their results, mainly due
      to the differences between the perceived morbidity and the treated morbidity,
      respectively established by each one of them. The objective of our study is to
      compare perceived morbidity with treated morbidity in the rural environment of
      Salamanca Province. METHODS: Data on morbidity obtained by the system of register
      in primary health care of the Community of Castilla y Leon in five base health
      areas of Salamanca Province, are compared with data obtained by interview survey
      in those areas during the same period of time. RESULTS: The three first causes of
      morbidity were: Diseases of Respiratory System, Digestive System and Circulatory
      System according to the home survey and Infectious and Parasite Diseases,
      Supplementary Classification and Signs, Symptoms and improperly Defined Morbid
      Status, according to registers. CONCLUSIONS: Taking into account the results
      obtained, the differences between both sources were statistically significative
      and the greatest differences were found in the group of Signs and improperly
      defined Morbid Status, Infections Diseases and the Supplementary Classification.

PMID- 7732316
TI  - [Time trends of infections in orthopedic and traumatologic surgery].
AB  - BACKGROUND: We have carried out a prospective study among 2,047 patients,
      operated in the Department of Traumatology of "La Paz" Hospital during two years
      in order to know the time trend of nosocomial infection. METHODS: All the
      operated patients have been included in the Study. Several variables have been
      collected (age, kind of surgery, infection, day of infection onset). Information
      was collected from the patient's clinical history and evolution and processed
      with the Sigma programme. RESULTS: The total percentage of infection was 10.06%;
      it was 7.63% in clean surgery and 26.79% in dirty surgery. Wound was the most
      frequent location of infection, followed in order of frequency by urine,
      respiratory system and sepsis. Since the patient is operated, there are two
      periods when infection increase significantly; those are between the 7-10 and 25
      30 post operation days. This tendency is typical of wound and urine infections;
      but in septicaemia, infection appears about the third post operation day in dirty
      surgery and about the 14th day in clean surgery. When studying the moment of
      patients's infection in clean surgery, a quick increase of wound infection is
      obtained in the second week, going from 33% (the 7th day) to 78% (the 14th day);
      next the curve slope diminishes down to 100% (the 61st day). In dirty surgery,
      the initial increase of wound infection is greater (54% on infections appear the
      7th day) and next it slows (64% of infections appear the 14th day and 100% are
      present the 45th day). CONCLUSIONS: It is necessary to reduce the infection rate
      in clean surgery mainly by improving surgical prophylaxis. The risk of infection
      appears earlier in dirty surgery than in clean surgery; for this reason, we shall
      insist upon its treatment (not prophylaxis) at the moment of the operation.
      Surveillance of infection signs must be intensified at maximum during the first
      post-operation week for dirty surgery and in the second week for clean surgery.

PMID- 7732317
TI  - [Community health pharmacists' situation in the framework of the Spanish State.
      Analysis of their functions and competence in the matter of food hygiene in the
      Community of Valencia].
AB  - BACKGROUND: We intend to show the Community Health pharmacists's situation in the
      different Autonomous Communities of the State, independently from their health.
      With regard to the Community of Valencia, we propose to integrate the Community
      Health pharmacists in the health structures of Health Areas, so that they can
      better fulfil their duties: specially Food Hygiene. METHODS: The information
      provided by the Health Services of each Autonomous Community has been used. Data
      from the Community of Valencia come from the Public Health General Direction and
      from Valencia Health Service of Generalidad Valenciana. Official criteria of
      periodical inspection in order to study needs have been put into practice. Data
      process has been computerized. RESULTS: Two kinds of Autonomous Communities have
      been identified depending on wether they have carried out or not the
      reorganization and/or the reassignment of duties of Community Health pharmacists.
      The distribution of Community Health pharmacists in the Autonomous Community of
      Valencia is shown in its health map, as well as the needs of surveillance for
      industries and food establishments within a pharmaceutic scope. CONCLUSIONS: The
      necessity of adapting the figure of the Community Health pharmacist to the Health
      General Law appears evident, particularly to health structures in the Areas; as
      well as the convenience of not making the chemist's shop possession compatible
      with the rest of duties assigned to this pharmacist's Body.

PMID- 7732318
TI  - [A sociodemographic study of pregnant women and relation to pregnancy
      acceptance].
AB  - BACKGROUND: Control of normal pregnancy in the scope of primary Health care has
      been implemented recently; this is the reason why, many factors which have an
      influence on the use of this service, still remain unknown. We carried out this
      descriptive study in two Primary Health Care Centers of the VIII Health Area in
      Asturias, in order to approach the pregnant woman's profile from our primary
      health care centers, and to study the relation between pregnancy acceptance and
      sociodemographic characteristics. METHODS: The social histories of all women, who
      requested health care for their pregnancy during 1991, were collected; the most
      interesting sociodemographic variables and those ones directly related to
      pregnancy were obtained. RESULTS: Out of a total of 139 women, the mean age was
      0.4 0.0006. There is a 16% of unmarried women. In relation with the pregnancy
      acceptance or desire, it was found that 31% of women did not desire it and this
      rejection was greater among unmarried women, younger than 20 years, (p = 0.0002)
      among those ones, whose contraceptive method had failed, (p = 0.0000) and among
      those ones, whose relations with their family were bad or not good enough (p =
      0.0004). CONCLUSIONS: A pregnant woman's profile, from our health centers, is
      obtained. It is necessary to develop health education programmes and family
      planning in the groups of women with higher number of not desired pregnancies,
      (young unmarried women).

PMID- 7732319
TI  - [The value of lidocaine-prilocaine cream in the surgery of detached ears].
AB  - The possibility to obtain a skin anaesthesia using only an ointment may be very
      usefull for outpatient surgery. Recently available in France, the lidocaine
      prilocaine cream give an interesting local anaesthesia. We have used this new
      presentation as skin preparation before otoplasty for 10 patients. As the local
      anaesthesia injections are then performed without pain, the comfort of the
      patient is greatly improved. Furthermore, it is easy to sue and without side
      effect. The main disadvantage consists in the action delay of one hour, with the
      necessity to ask the patient to come earlier.

PMID- 7732320
TI  - [Surgery and curietherapy of keloids].
AB  - Postoperative irradiation of keloids allows a decrease of the recurrence rate by
      about 50%, compared to surgery alone. A review of the literature illustrates the
      benefits due to the irradiation, and describes the techniques available. The
      Iridium 192 interstitial brachytherapy, with per-operative implantation of the
      plastic tubes and immediate irradiation of 20 Gy at 5 mm depth, is detailed as
      used by French teams. The analysis of the published results allows to recommend
      this technique which is tailored to each clinical situation, safe, and easy to
      perform by the surgeon.

PMID- 7732321
TI  - [Reconstruction of the orbit floor using a resorbable polydioxanone (PDS degree)
      cup. Analysis of a series of 71 cases].
AB  - A 71 patients series is presented, concerning primary orbital floor
      reconstruction by a polydioxanone cup (PDS degree) which has been used for five
      years. The technical data and surgical procedure are exposed. No infection either
      intolerance manifestation has been observed until the materiel was resorbed. Two
      early displacements of the implant are reported, due to a technical fault during
      the insertion of the cup. Only one late enophtalmy was observed for a patient
      with a large orbital floor defect. The loss a the rigidity of the polydioxanone
      seems to be relatively fast (probably 2-3 months) and leads to contraindicate its
      use in cases of large osseous traumatic defects. In all other cases, this
      surgical technique seems to be very useful.

PMID- 7732322
TI  - [A cephalometric study of the pterygoid process during growth].
AB  - This study consists in a three dimensional cephalometric approach of the
      pterygoid process and its relationships with the neighbouring cranio-facial
      structures, using biostatistical analysis. The authors present the results of
      this method comparing the variations of the pterygoid process in relation to the
      variations of the basi-cranium and the face.

PMID- 7732323
TI  - [Uncommon fungal maxillary sinusitis of dental origin due to Scedosporium
      prolificans].
AB  - This is the first case report of an exceptional maxillary infection due to
      Scedosporium prolificans. This recently discovered fungus was identified in the
      sinus. In the literature, it has been observed at different locations.
      Identification requires careful sample taking for mycology and pathology studies
      emphasizing the importance in maxillary surgery. This pathogenic fungus is very
      invasive, particularly in immunodepressed or immunocompromised patients.
      Therapeutic modalities vary with the patient's immune status.

PMID- 7732324
TI  - [Chondroblastoma of the temporomandibular region. Review of the literature
      apropos of a case].
AB  - A case of chondroblastoma of the temporomandibular area in a 56 years old female
      patient is presented. We proposed a discussion about clinical, histological
      diagnosis and therapy.

PMID- 7732325
TI  - [Maxillofacial manifestations of Steinert's myotonic dystrophy. Clinical and
      therapeutic aspects].
AB  - The craniofacial manifestations, together with teleradiographic and cephalometric
      findings, of Steinert's dystrophy were examined based on a review of the
      literature and the clinical features of several patients with myotonic dystrophy
      leading to the diagnosis of Steinert's disease. The prevalence of the functional
      impairments due to facial deformation varies with the severity of the disease,
      suggesting early interceptive treatment supported by orthopaedic care and
      rehabilitation therapy of orofacial functions. Surgery involves bimaxillary
      osteotomy which can improve mastication and facial morphology. Operative risks
      should be carefully identified with adequate explorations before surgery.

PMID- 7732326
TI  - [Malignant xanthogranuloma of the mandible. Presentation of a case and review of
      the literature].
AB  - A malignant xanthogranuloma located in the mandible presented as a tumefaction of
      the alveolar crest with labiomental hypoaesthesia in a 52-years-old woman. The
      patient was treated with combined chemoradiotherapy and remained in complete
      remission for 14 years. Epidemiologic features (age, sex, race) of this tumour
      are discussed in light of the 24 cases reported in the literature. Histology
      features and possible treatment protocols as well as observed results are
      discussed. Five-year survival rate in malignant cervicofacial xanthogranulomas is
      estimated at 48%.

PMID- 7732327
TI  - [Treatment of fractures of the mandibular condyle].
AB  - The current treatment of mandibular condyle fractures still remains unclear. The
      choice between surgical and conservative treatment is difficult in current
      clinical practice. Every possible treatments are here presented to give the oral
      and maxillofacial surgeon a better knowledge about what to do in presence of a
      mandibular condyle fracture.

PMID- 7732328
TI  - Noise-induced hearing loss. Literature review and experiments in rabbits.
      Morphological and electrophysiological features, exposure parameters and temporal
      factors, variability and interactions.

PMID- 7732329
TI  - Meta-analysis of the effect of placebo on the outcome of medically treated reflux
      esophagitis.
AB  - BACKGROUND: To ascertain the placebo-induced effect in the treatment of reflux
      esophagitis, we reviewed all the English-language literature concerning the
      results of placebo-controlled trials of erosive/ulcerative esophagitis from 1976
      to 1990. Twenty-two studies fulfilled our meta-analytic criteria. RESULTS: After
      4 to 8 weeks of treatment, active drugs (cimetidine, ranitidine, nizatidine,
      omeprazole, metoclopramide, sucralfate) were significantly more effective than
      placebo in the healing of esophagitis, with a pooled rate difference (PRD) of
      0.22 in favor of the active drug, an odds ratio (OR) of 2.57 (confidence interval
      (CI) = 2.0-3.3). Pooled mean healing rate (+/- SD) with the active drug was 47.3
      +/- 24.0%, as compared with 26.8 +/- 18.0% obtained with placebo after 4 to 8
      weeks of treatment. With regard to symptomatic response, complete disappearance
      of symptoms was observed in an average of 31.6% active-treated patients and in
      11.8% of placebo-treated patients, respectively. The PRD was 0.20, and the OR
      2.25 (CI = 1.65-3.06). The incidence of side effects was not statistically
      different for the two treatment groups. CONCLUSION: Placebo is a relatively
      inactive drug in the short-term treatment of erosive ulcerative reflux and does
      not appear to change the natural history of the disease.

PMID- 7732330
TI  - The effect of cisapride and ranitidine as monotherapies and in combination in the
      treatment of uncomplicated gastric ulceration.
AB  - BACKGROUND: Stimulation of gastric motility has been supposed to accelerate the
      healing of gastric ulcer. The combination of the prokinetic drug cisapride and
      the H2 blocker ranitidine was tested in the treatment of uncomplicated gastric
      ulcer. METHODS: Cisapride, 20 mg twice daily (Cis), and ranitidine, 150 mg twice
      daily (Ran), were given as monotherapies and in the combination 20 mg cisapride
      and 150 mg ranitidine daily (Cis + Ran) for a maximum of 8 weeks. The study was
      multicentre, randomized, and double-blind. RESULTS: A total of 197 patients were
      included. Healing rates in the per-protocol analysis after 4 and 8 weeks'
      treatment were 61%/84%, 52%/69%, and 61%/92% for the Cis + Ran (n = 56), Cis (n =
      58), and Ran (n = 59) treatment groups. No statistically significant difference
      in healing rates was seen when comparing Cis + Ran with the monotherapies.
      Symptom relief at the end of treatment was significantly better in the Ran group
      than in the Cis + Ran group with regard to epigastric pain (p = 0.01) and
      vomiting (p = 0.05). Patients' global evaluation of treatment was in favour of
      Ran in comparison with Cis + Ran treatment (p = 0.04). CONCLUSIONS: Combination
      of cisapride and ranitidine in the treatment of gastric ulcer did not enhance the
      healing rate or improve symptom relief in patients treated for uncomplicated
      gastric ulcer when compared with the monotherapies.

PMID- 7732331
TI  - Pantoprazole is superior to ranitidine in the treatment of acute gastric ulcer.
AB  - BACKGROUND: Pantoprazole is a newly developed gastric H+/K(+)-adenosine
      triphosphatase inhibitor with a potent and long-acting inhibitory effect on
      gastric acid secretion. METHODS: In a double-blind multicenter study with 28
      centers in Germany, pantoprazole (40 mg before breakfast) was compared with
      ranitidine (300 mg at bedtime) with regard to healing rates, time until healing,
      symptom relief, and tolerability. A total of 248 outpatients with benign gastric
      ulcer were included. RESULTS: The healing rates after 2, 4, and 8 weeks were 37%,
      87%, and 97%, respectively, in the pantoprazole and 19%, 58%, and 80% in the
      ranitidine group. The differences between the two groups were significant at 2
      weeks (p < 0.01), 4 weeks (p < 0.001), and 8 weeks (p < 0.001; Cochran/Mantel
      Haenszel method). Ulcer healing proceeded significantly faster with pantoprazole
      (p < 0.001; Uleman's U-test). Both treatments were well tolerated. CONCLUSIONS:
      Pantoprazole appears to be superior to ranitidine in gastric ulcer healing.

PMID- 7732332
TI  - Association of Helicobacter pylori gastric infection with the suppressed Thomsen
      Friedenreich antigen natural humoral response.
AB  - BACKGROUND: A low natural humoral immune response to Thomsen-Friedenreich antigen
      (TFA) is a general phenomenon in patients with cancer, including gastric cancer,
      and in some premalignant conditions. It has been also shown that Helicobacter
      pylori infection is associated with increased risk of gastric cancer. The
      possible link between the TFA immune response and H. pylori infection was
      investigated. METHODS: Enzyme-linked immunosorbent assay with H. pylori cell
      surface glycine extract as antigen and microhemagglutination of neuraminidase
      treated blood group O donor erythrocytes were used for evaluation of IgG H.
      pylori antibody and TFA agglutinin levels in sera from patients with gastric
      cancer (n = 39) or ulcer of the stomach (n = 36) and controls (n = 49). RESULTS:
      The tendency to an inverse relationship between the two events was found in all
      groups studied, including cancer. H. pylori-seronegative persons had higher TFA
      natural antibody titer than the related H. pylori-seropositive groups. When log2
      of TFA antibody titer > 4 for strong TFA responders and H. pylori relative
      antibody activity > 25 for H. pylori-seropositive persons were chosen as cut-off
      limits, the association was statistically significant (p < 0.02). TFA antibody
      level was decreased in cancer patients as compared with controls (p < 0.002). No
      relation to age, stage of the disease, or tumor morphology was noted. CONCLUSION:
      The data suggest that the TFA natural immune response, which is known to
      participate in tumor-host relationships, is also involved in H. pylori-host
      interactions, probably as a natural factor of resistance against H. pylori
      infection.

PMID- 7732333
TI  - Increases in plasma motilin follow each episode of gallbladder emptying during
      the interdigestive period, and changes in serum bile acid concentration correlate
      to plasma motilin.
AB  - BACKGROUND: The relationship between each single period of gallbladder emptying
      during the migrating motor complex (MMC) cycle and changes in concentration of
      plasma motilin and serum bile acids is unknown. METHODS: The variations in the
      concentration of plasma motilin and serum bile acids in relation to
      interdigestive gallbladder motility and the MMCs was studied in nine healthy male
      volunteers. A method combining biliary scintigraphy (99mTc-labelled dimethyl
      iminodiacetic acid) and continuous pressure recording from the antroduodenal
      region was used. RESULTS: During 9 MMC cycles a total of 15 episodes of
      gallbladder emptying were observed with a median (range) duration of 25 min (15
      45 min). Each episode of gallbladder emptying was followed by a steep increase in
      plasma motilin, reaching a median value of 30 pmol/l (13-43 pmol/l),
      corresponding to an increase of 18 pmol/l (4-33 pmol/l). The increase in plasma
      motilin started at the beginning of gallbladder emptying, but the peak value was
      not reached until a median of 20 min (10-45 min) later. Low plasma motilin
      concentrations were found between the emptying periods in cases with two or more
      emptying during the MMC cycle. The serum concentration of bile acids also showed
      a cyclic variation in relation to gallbladder motility. During periods of
      gallbladder emptying serum bile acid concentration had a median value of 1.78
      mumol/l, as compared with a median value of 1.17 mumol/l during periods of
      gallbladder filling. This difference did not reach significance, however. In the
      pooled data from all subjects, a significant correlation (p < 0.01) between the
      serum concentration of bile acids and plasma concentration of motilin was found.
      CONCLUSION: Gallbladder emptying was followed by a steep increase in plasma
      motilin concentration, and in cases of two or more emptying periods during the
      MMC cycle the concentration decreased in between. The shape of the serum bile
      acid profile is dependent on the intestinal transport and absorption of bile
      acids, and the significance of the cyclic variation in serum concentration of
      bile acids in relation to plasma motilin, gallbladder motility, and MMC needs
      further investigation.

PMID- 7732334
TI  - Gallbladder emptying during high-dose cholecystokinin infusions. Effect in
      patients with gallstone disease and healthy controls.
AB  - BACKGROUND: Impaired gallbladder emptying is a pathogenetic factor in gallstone
      formation. To test whether gallbladder motility can be improved by high-dose
      cholecystokinin (CCK), gallbladder emptying was measured sonographically in 21
      patients with cholesterol gallstone disease and 6 healthy controls. METHODS: The
      effects of CCK infusions of 0.06 IDU/kg.min (group A, n = 11) and 0.12 IDU/kg.min
      (group B, n = 10) were compared with the response to a standard CCK infusion
      (0.02 IDU/kg.min). Controls received CCK at all infusion rates. RESULTS: The
      ejection fraction was smaller after CCK infusion of 0.06 IDU/kg.min than after
      the standard stimulus (group A, 52 +/- 10 versus 64 +/- 10%, p < 0.05; controls,
      66 +/- 10 versus 91 +/- 3%, p < 0.05). After infusion of 0.12 IDU/kg.min CCK
      ejection fractions decreased even more (group B, 44 +/- 16 versus 65 +/- 12%, p <
      0.05; controls, 54 +/- 12 versus 91 +/- 3%, p < 0.05). High-dose CCK infusions
      shortened the ejection period markedly, whereas the ejection rate remained
      unaltered. CONCLUSIONS: High-dose CCK does not improve gallbladder motility but
      blocks the ejection process early, leading to reduced gallbladder emptying in
      gallstone patients and healthy subjects.

PMID- 7732335
TI  - Sulfamethizole absorption test for the assessment of gastric emptying. Comparison
      with scintigraphic method.
AB  - BACKGROUND: To investigate whether the sulfamethizole absorption test can be
      applied for the assessment of gastric emptying, we measured comparatively plasma
      sulfamethizole concentration and gastric emptying as determined by scintigraphy
      in 15 subjects. METHODS: After the ingestion of a solid-liquid meal that
      contained sulfamethizole and radioisotope (technetium-99m-labeled
      diethylenetriaminepentaacetic acid), the plasma sulfamethizole concentrations
      were measured every 15 to 60 min up to 180 min. The initial emptying time
      (duration after ingestion until 10% reduction in radioactivity of the stomach)
      and the exponential curve in the cumulative reduction of radioactivity were used
      as indicators of gastric emptying. RESULTS: The initial emptying time was
      significantly correlated with the sulfamethizole concentration at 15 min after
      ingestion (r = -0.64, p < 0.05). A close correlation was observed between the
      rate of decrease in radioactivity and sulfamethizole concentration at 60 min
      after ingestion (r = 0.80, p < 0.001). CONCLUSIONS: The sulfamethizole absorption
      test can be used for the evaluation of gastric motility. Two points of
      measurement, 15 and 60 min after ingestion, are sufficient to demonstrate the
      initial and subsequent gastric emptying.

PMID- 7732336
TI  - Comparison between physiologic and erythromycin-induced interdigestive motility.
AB  - BACKGROUND: The last part of duodenal phase III of the migrating motor complex
      behaves as a retroperistaltic pump. We have compared the phase-III-like
      gastroduodenojejunal activity induced by erythromycin with the naturally
      occurring phase III, focusing on peristaltic patterns. The effect of two doses of
      erythromycin, 3 mg/kg/h and 12 mg/kg/h (in four subjects), or saline, given
      intravenously for 15 min, was studied in nine fasting healthy subjects (five men
      and four women). METHODS: Motility was recorded on three different days. On one
      day standard 5-h eight-channel antroduodenojejunal manometry was performed and
      saline infused 30 min after the first phase III. On the other two study days,
      erythromycin in the low or the high dose was infused and recording performed for
      another 2-h period. RESULTS: The low dose of erythromycin induced a phase III in
      the stomach in all subjects within 12.8 +/- 1.4 min. In contrast, the higher dose
      did not induce phase-III activity within the 1st h after infusion but induced
      marked antral pressure waves. The duration of the erythromycin-induced phase III
      and the naturally occurring antral phase III was 4.7 +/- 1.7 and 1.9 +/- 0.3 min,
      respectively (p < 0.01). The duration of the erythromycin-induced phase III in
      the proximal jejunum was 44% shorter than the spontaneous one (p < 0.01). The
      propagation velocity, from the proximal duodenum to the proximal jejunum, of the
      erythromycin-induced phase III was slower than that of the spontaneous phase III:
      5.7 +/- 0.9 and 15.9 +/- 3.9 cm/min, respectively (p < 0.01). In the proximal
      duodenum the proportion of retrograde pressure waves (of all propagating waves)
      was about 10% in early phase III, increasing to about 85% in late phase III in
      both the spontaneous and erythromycin-induced phase III. In the proximal jejunum
      retrograde pressure waves were not observed in phase III. CONCLUSIONS:
      Erythromycin given in a low dose is very effective in inducing phase-III-like
      motility. The last part of duodenal phase III is characterized by
      retroperistalsis also when this motility phase is induced by erythromycin.

PMID- 7732337
TI  - Enteral glutamine increases growth and absorptive capacity of intestinal mucosa
      in the malnourished rat.
AB  - BACKGROUND: Glutamine is an important nutrient for the small intestine.
      Beneficial effects of glutamine could be related to restoration of optimal
      intestinal barrier functions. METHODS: Thirty-eight Sprague-Dawley rats were
      allocated to three main groups. Experimental groups (n = 22) were malnourished
      and laparotomized. Sham groups (n = 11) were laparotomized without prior
      malnutrition. These groups were refed with or without oral glutamine for 3 days.
      The control group (n = 5) was given chow. Permeability was assessed by the 6-h
      urinary recovery of orally given polyethylene glycols, PEG 400/1000. Mucosal
      proliferation was estimated by DNA content and 1-h incorporation of 3H-thymidine
      intravenously. RESULTS: In the malnourished groups glutamine resulted in higher
      thymidine incorporation (p < 0.05) and better absorption of small PEG molecules
      (p < 0.05). CONCLUSION: The effects of oral glutamine on permeability after
      malnourishment and laparotomy are proposed to be related to an increase in
      absorptive area.

PMID- 7732338
TI  - Subclinical coeliac disease is a frequent cause of iron-deficiency anaemia.
AB  - BACKGROUND: Although it is known that anaemia may be the only presenting symptom
      in coeliac disease, prevalence figures of unsuspected coeliac disease in anaemic
      patients are not available. The aim of this study was to assess the clinical
      usefulness of antigliadin and antiendomysial antibody tests in the diagnostic
      algorithm of anaemic patients. METHODS: Two hundred consecutive anaemic patients
      were tested for antigliadin antibodies, and those positive were also tested for
      antiendomysial antibodies. All patients positive for antigliadin and
      antiendomysial antibodies underwent intestinal biopsy. RESULTS: Sixteen patients
      were antigliadin antibody-positive, and 10 were also antiendomysial antibody
      positive. In all 10 a jejunal biopsy was consistent with coeliac disease
      (prevalence, 5%). This prevalence rose to 8.5% when patients with macrocytic
      anaemia or with microcytic anaemia due to previous bleeding or responsive to oral
      iron therapy were excluded from the calculation. CONCLUSIONS: Coeliac disease is
      a frequent cause of iron-deficiency anaemia, and antigliadin and antiendomysial
      antibody tests should be always performed in the diagnostic algorithm of anaemic
      patients.

PMID- 7732339
TI  - Circulating granulocyte antibodies in first attacks of colitis.
AB  - BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) have recently been
      demonstrated in the sera of patients with inflammatory bowel disease (IBD).
      METHODS: The presence of ANCA was studied in 107 sera obtained during 1 year from
      48 patients with a first attack of IBD and in 33 such sera from 19 patients with
      infectious or infectious-type colitis (non-relapsing colitis (NRC)). RESULTS: In
      65% (31 of 48) of the IBD patients positive immunofluorescence reactivity against
      granulocytes was observed, compared with in 5% of the NRC patients. No
      significant difference in granulocyte reactivity was found either between
      patients with colonic Crohn's disease and those with ulcerative colitis or
      between active and inactive phases of the disease. Most of the sera showed a
      perinuclear immunofluorescence staining pattern (68%), in contrast to the
      classical cytoplasmic staining pattern seen in Wegener's granulomatosis. In sera
      obtained at the first visit from the 31 IBD patients with positive granulocyte
      reactivity a hitherto unknown antibody against beta-glucuronidase was found in
      42%, whereas in 45% the specificity was not identified. Other antibodies, rarely
      seen, were directed against myeloperoxidase, lactoferrin, elastase, and cathepsin
      G. No antibody directed against lysozyme was detected. CONCLUSIONS: Positive
      granulocyte reactivity practically excluded NRC and was seen in more than half of
      IBD patients. Antibodies against beta-glucuronidase were common, but still almost
      half of the antibodies remained unknown.

PMID- 7732340
TI  - Mesalazine suppositories versus hydrocortisone foam in patients with distal
      ulcerative colitis. A comparison of the efficacy and practicality of two topical
      treatment regimens.
AB  - BACKGROUND: Topical treatment is effective in patients with distal ulcerative
      colitis. This trial compares the efficacy, safety, and practicality of 4 weeks'
      treatment with 500 mg mesalazine suppositories with those of 178 mg
      hydrocortisone foam, both given twice daily. METHODS: Seventy-nine patients with
      distal ulcerative colitis were stratified on the basis of the extent of the
      disease (proctitis and proctosigmoiditis) and randomized to one of the treatment
      groups. A disease activity index (DAI) based on symptoms and endoscopic findings
      was calculated. The patients evaluated the practicality of the treatment
      regimens, patients compliance was measured, and histologic findings recorded.
      RESULTS: Of all the patients 22% and 38% were complete responders after 2 and 4
      weeks, respectively. Median DAIs in the mesalazine and hydrocortisone groups
      before and after 2 and 4 weeks' treatment were 14, 6, and 4, and 13, 8, and 6,
      respectively. The difference between the treatment groups was statistically
      significant (p = 0.02) due to a better effect of mesalazine in patients with
      proctitis. Patients' evaluation of practicality and patient compliance were
      statistically significantly better in the mesalazine group. CONCLUSIONS: Both
      treatment regimens are effective; mesalazine suppositories seem to be the
      preferred alternative.

PMID- 7732341
TI  - Factors associated with participation in screening for colorectal cancer with
      faecal occult blood testing.
AB  - BACKGROUND: Factors associated with attending screening for colorectal cancer
      with faecal occult blood testing was studied. METHODS: Sixty-eight per cent of
      34,144 subjects participated in the primary screening and/or rescreening in a
      randomized screening study. The mortality and causes of death in the two groups
      were studied. A sample of the subjects received a questionnaire, in which they
      were asked about their reaction to the invitation. A statistical sample was
      called for a telephone interview. RESULTS: The mortality among the non-attenders
      was higher than among the attenders (p < 0.001), which might reflect a higher
      morbidity among the non-attenders. The mortality was equal in the test and
      control groups. There was no difference among the attenders and non-attenders who
      had a full or 50% pension. Among immigrants the attitude to screening was less
      positive among those born in 1918 but was the same as that of the whole group
      among those born in 1929. Significantly fewer persons among the non-attenders
      than among the attenders could be reached for a telephone interview (p < 0.001).
      CONCLUSION: There is a possibility that the compliance can be increased. The non
      attenders' attitude to screening was more negative than that of the attenders.

PMID- 7732342
TI  - The role of oral administration of oatmeal fermented by Lactobacillus reuteri
      R2LC on bacterial translocation after acute liver failure induced by subtotal
      liver resection in the rat.
AB  - BACKGROUND: Previous experimental studies showed that a disturbed ecology of the
      enteric bacterial population might contribute to the occurrence of bacterial
      translocation from the gut in acute liver failure (ALF). METHODS: In the present
      study the effects of oral administration of exogenous Lactobacillus reuteri R2LC
      and oat fiber on bacterial overgrowth and translocation and on enterocyte protein
      contents were investigated in rats with ALF induced by subtotal liver resection.
      The oatmeal soup base was anaerobically inoculated with L. reuteri R2LC and
      fermented for 15 h. The animals were then fed with fermented or unfermented
      oatmeal or saline daily for 6 days before the experimental procedure. RESULTS:
      The incidence of bacterial translocation to the systemic circulation was nil and
      17% in rats subjected to sham operation with saline or 90% hepatectomy with
      fermented oatmeal, respectively, and 80-90% and 34-50% in rats subjected to
      hepatectomy with saline or unfermented oatmeal. One rat treated with fermented
      oatmeal had positive bacterial growth in mesenteric lymph nodes (MLN), which was
      significantly lower than in hepatectomized rats with saline or unfermented
      oatmeal (80-100% and 50-67%). No significant differences was demonstrable between
      hepatectomized animals with oral administration of fermented or unfermented
      oatmeal as compared with sham-operated rats. The number of anaerobic bacteria,
      Gram-negative anaerobes, and Lactobacillus decreased significantly, and the
      number of Escherichia coli increased in the distal small intestine and colon in
      hepatectomized animals with saline or unfermented oatmeal, as compared with
      animals subjected to sham operation or hepatectomy with fermented oatmeal.
      CONCLUSIONS: The occurrence of bacterial translocation from the gut in 90%
      hepatectomy-induced ALF could be prevented by fermented oatmeal, which implies
      possibilities for biologically balancing the enteric bacterial ecology.

PMID- 7732343
TI  - Intestinal metaplasia in H. pylori gastritis.

PMID- 7732344
TI  - What are the real problems for patients with functional dyspepsia?
AB  - BACKGROUND: Patients with functional dyspepsia (FD) have more complaints than
      just the dyspepsia. METHOD: One hundred FD patients were assessed with regard to
      psychologic, medical, and social factors, before randomization, in a study of
      cognitive therapy. They were asked to list their main problem areas or 'target
      complaints'. RESULTS: Dyspepsia was the third most frequent target complaint (26
      patients), and anxiety was the most frequent one (65 patients). Patients
      identifying dyspepsia as a target complaint differed from the other FD patients
      in several aspects. They had significantly more dyspeptic symptoms (p < 0.05) and
      scored significantly higher on multiple somatic complaints (p = 0.001),
      depression (p = 0.025), general psychopathology (p = 0.043), the global
      assessment scale (p = 0.001), and the General Health Questionnaire (p = 0.040).
      However, they did not have more somatic predisposing factors like consumption of
      alcohol and coffee or infection with Helicobacter pylori than the patients with
      other target complaints. CONCLUSIONS: Anxiety and not dyspepsia was the most
      frequent target complaint, and patients who identified dyspepsia as a target
      complaint did not have more somatic predisposing factors.

PMID- 7732345
TI  - [Why do farmers die more often from lung diseases?].
AB  - During the period 1988-1992 deaths from lung diseases were more frequent among
      the farming population according to Swiss mortality data. The age-standardized
      proportional mortality rate (PMR) is 127 for all the lung diseases (ICD-8 460
      519), 140 for bronchitis and asthma (ICD-8 490-493), 137 for asthma alone (ICD-8
      493) and 841 for pneumoconiosis due to organic dust (ICD-8 516.1 + .2). Stock
      farmers showed a mortality pattern for chronic obstructive pulmonary disease
      opposite to that of vegetable farmers and wine-growers. This increased mortality
      among farmers is paradoxical in the light of the more frequent tolerance for
      aeroallergens among the children of farmers, the conservative style of housing
      and living as well as received ideas about working in natural and therefore
      healthy air. Insufficient knowledge of the multifactorial risks of natural
      pathogenic organic substances and of dangerous work are just as important for the
      pathogenesis of these diseases and deaths as the changed social and cultural
      values with the consequences on insurance policy. These factors affect optimal
      prophylaxis (limitation of air pollution, safety measures, job change and
      measures in order to achieve adequate social security).

PMID- 7732346
TI  - [Frequency of antibiotics-associated colitis in hospitalized patients in 1974
      1991 in "Comprehensive Hospital Drug Monitoring", Bern/St. Gallen].
AB  - In 3 divisions of internal medicine of teaching hospitals of the Comprehensive
      Hospital Drug Monitoring (CHDM) Foundation Bern/St Gallen, 42,920 patients
      consecutively admitted between 1974-1991 were investigated for adverse drug
      reactions. Of these 16,150 patients (38%) had received at least one systemically
      administered antibacterial drug during the hospital stay. Antibiotic-associated
      colitis included the following diagnoses: pseudomembranous colitis, hemorrhagic
      colitis and milder forms of colitis. We collected the data of these patients by
      searching for all diagnoses which might represent antibiotic-associated colitis
      (from the list of WHO adverse drug reaction terminology). 9 individual patients
      with one episode of probable antibiotic-associated colitis were found. In 5 of
      these cases, only one drug given during the hospital stay seemed to be
      implicated. An additional 32 patients were admitted with antibiotic-associated
      colitis in relation to treatment with the same groups of drugs before hospital
      admission. Based on the exposure pattern of the 9 patients with antibiotic
      associated colitis compared to all patients exposed during hospital stay, we
      estimated the following frequencies related to the drug groups with at least
      1,000 patients exposed: for all antibacterial chemotherapeutics 0.6/1000 (0.25
      1.06); all penicillins 0.6/1000 (0.22-1.32), for benzyl-, phenoxy-, ureido-,
      isoxazolyl penicillins and methicillin 2.0/1000 (0.42-5.92) and aminopenicillin
      or analogues, with or without clavulanic acid 0.6/1000 (0.18-1.35). For
      cephalosporins the frequency is 1.4/1000 (0.17-5.12). Under sulfonamides combined
      with trimethoprim or related substances (5077 exposed patients) and
      fluoroquinolones (1043 exposed patients) no case was observed.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7732347
TI  - [Cerebral toxoplasmosis with central diabetes insipidus and panhypopituitarism in
      a patient with AIDS].
AB  - Endocrine disorders in the course of HIV infection are often a result of
      opportunistic infections of endocrine organs. We describe the case of a 30-year
      old HIV positive man in whom diabetes insipidus developed initially with no
      abnormal findings in cranial magnetic resonance imaging. 2 months later the
      patient presented with symptoms of panhypopituitarism. At this time,
      neuroradiologic examination was consistent with cerebral toxoplasmosis. Symptoms
      and neuroradiologic findings improved after treatment for cerebral toxoplasmosis.
      Toxoplasmosis is the most frequent opportunistic infection of the brain in
      patients with AIDS. In HIV positive patients with malfunction of the hypothalamic
      hypophyseal system cerebral toxoplasmosis must be considered in differential
      diagnosis. Treatment of this disorder may alleviate symptoms and signs of
      endocrine malfunction.

PMID- 7732348
TI  - [Occupational activities and allergic respiratory manifestations].
AB  - The authors review aspects of occupational asthma that are important for the
      practitioner. Insurance problems are dealt with in the light of local
      regulations. Detailed chapters are devoted to baker's asthma (various
      aeroallergens), to plastic workers and painters (isocyanates) and to respiratory
      diseases among farmers. Finally, a list of other occupations in which asthma
      typically occurs is given. The responsibility of practitioners in charge of young
      patients about to choose their future profession is underlined.

PMID- 7732349
TI  - [Concerning: K. Boggian, H.J. Leu, J Schneider, M. Turina, D, Oertle: True
      aneurysm of the ascending aorta in HIV disease (Schweiz Med Wochenschr 1994; 124:
      2083-2087)].

PMID- 7732350
TI  - [Scientific raisins from 125 years of SMW (Swiss Medical Weekly). Lump-sum
      payment in the health insurance system. 1906].

PMID- 7732351
TI  - [Hyperventilation test: a noninvasive screening test for coronary vasospasm].
AB  - 3 patients with coronary vasospasms in different clinical situations are
      presented. One patient had typical Prinzmetal angina but coronary arteries
      without significant stenosis. One patient without typical angina pectoris showed
      sudden significant ST elevations on anterior and lateral ECG tracings accompanied
      by typical ischemic chest pain. At angiography, a 70% LAD stenosis was found
      without high degree lesions. One patient (aged 30 years) had a documented
      anterior infarction with angiographically normal coronary arteries. In all these
      cases coronary vasospasms were recognized as the underlying cause of the
      symptoms. All the patients were treated with calcium channel blockers and have
      been asymptomatic since. Currently available data comparing the diagnostic value
      of hyperventilation with other tests for coronary vasospasms, such as ergonovine
      or acetylcholine, are discussed. The hyperventilation test can be recommended as
      the first test in the work up of suspected vasospastic angina pectoris.

PMID- 7732352
TI  - [Isolated lung transplantation--evaluation of patients and initial results].
AB  - Between November 1992 and May 1994 we performed 10 single and 5 double lung
      transplants in patients with end-stage lung diseases due to
      lymphangioleiomyomatosis (4), cystic fibrosis (3), pulmonary hypertension (3),
      pulmonary fibrosis (3) and chronic obstructive lung disease (2). In the 13
      patients (87%) surviving for median 245 (19-567) days, FEV1 improved from median
      640 ml to 1410 ml and the 12-minute walk distance from median 315 to 1100 meters.
      10 patients (77%) enjoy a good or even excellent quality of life. 2 patients died
      11 and 62 days postoperatively, due to multi-organ failure and invasive pulmonary
      aspergillosis respectively. The main postoperative problems are fungal and
      cytomegalovirus infections and chronic rejection in the form of bronchiolitis
      obliterans. In Switzerland as elsewhere, lung transplantation has become an
      established modality for the management of end-stage diseases of the lung and
      pulmonary circulation.

PMID- 7732353
TI  - [Tuberculin tests in school leavers in canton Berne , Neuenburg and Wallis
      1992/1993].
AB  - To determine the prevalence of tuberculosis infection in Switzerland,
      standardized tuberculin tests using 2 units of tuberculin Berna PPD RT 23,
      administered by specially trained personnel, were performed on school leavers in
      3 Swiss cantons in 1992/1993. Of the 7036 school leavers, averaging 15 years of
      age, only 294 (4.18%) were not BCG-vaccinated. Non-vaccinated persons had
      tuberculin test indurations > 15 mm in 2.04% (6663 BCG vaccinated persons in
      1.14%). Calculations of potentially influential factors using stepwise ordinal
      polychotomous regression showed that tuberculin test indurations are
      significantly larger after BCG vaccination, as well as with increasing age at
      immigration from high prevalence tuberculosis countries. Indurations were smaller
      with increasing time passed since BCG vaccination, as well as in females. Pets at
      home did not significantly influence the size of tuberculin reactions.
      Theoretically the positive predictive value of tuberculin tests in Switzerland is
      small because of the low tuberculosis prevalence. From our data the maximal
      prevalence of infection in 15-year-olds is estimated at 0.91% (2.48% in the non
      vaccinated) in Swiss and 2.54% (9.77% in the non-vaccinated) in foreign born
      school children. These rates, higher than extrapolated from previous studies, are
      comparable to data from other industrialized countries. They do not warrant a
      change in BCG vaccination policy in Switzerland, which since 1987 requires BCG
      vaccination in children immigrating from countries with high tuberculosis
      prevalence only.

PMID- 7732355
TI  - The cold war's dirty secrets. Radiation experiments ignored ethics guidelines.

PMID- 7732354
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). A brief report on
      the discovery of the pathogen (Spirochaeta icterohaemorrhagiae nov. sp.) of so
      called Weil's disease in Japan and on current studies of the disease. 1916].

PMID- 7732356
TI  - Electric genes. Current flow in DNA could lead to faster genetic testing.

PMID- 7732357
TI  - The global tobacco epidemic.

PMID- 7732358
TI  - Utilization of scalp hair for evaluating epilepsy in male and female groups of
      the Pakistan population.
AB  - Concentrations of Fe, Cu, Zn, Cr, Mg and Ca are determined in scalp hair of adult
      epileptic and normal male and female subjects by atomic absorption spectroscopy.
      A total of 85 hair samples for normal male/female subjects and 78 of male/female
      epileptic subjects were analyzed within the respective age groups of 28 to 30 and
      24 to 27 years. The study showed higher average concentration of Zn, Fe and Cu in
      normal male subjects compared with the epileptic subjects. Levels of Ca, Mg and
      Cr were lower in normal male adults than those found in epileptic subjects.
      Epileptic females showed higher average concentrations of Zn, Ca and Cu. The
      correlation coefficient study indicated significant correlation (r > 0.589 at P =
      0.001) between Fe and Cr, Mg, Ca and Cu for epileptic females only. For normal
      male subjects Ca showed a strong correlation for Zn and Fe and for Cr and Ca. The
      regression analysis showed the significant role of Zn, Ca, Mg and Cr in scalp
      hair of normal and epileptic subjects. Accordingly, the metal-to-metal ratio
      analysis revealed critical Mg/Zn ratios as indicators of healthy (< 1) and
      epileptic (> 1) subjects. The ratio data are used for evaluation of the status of
      epileptic patients based on their ailment history.

PMID- 7732359
TI  - The Koshland years--a decade of progress.

PMID- 7732360
TI  - Musical ability.

PMID- 7732361
TI  - World Wide Web and molecular biology.

PMID- 7732363
TI  - Darwin in the headlines.

PMID- 7732362
TI  - Darwin in the headlines.

PMID- 7732364
TI  - An ominous blooding?

PMID- 7732366
TI  - Rockefeller strikes fat deal with Amgen.

PMID- 7732365
TI  - FDA puts the brakes on xenotransplants.

PMID- 7732367
TI  - NIH names behavioral research czar.

PMID- 7732368
TI  - NIMH: caught in the line of fire without a general.

PMID- 7732369
TI  - Envisioning an artificial retina.

PMID- 7732370
TI  - Dioxin receptor knocked out.

PMID- 7732371
TI  - Portrait of a lung.

PMID- 7732372
TI  - The emerging world of plant science.

PMID- 7732373
TI  - Exploring transgenic plants as a new vaccine source.

PMID- 7732374
TI  - Molecular genetics of plant disease resistance.
AB  - Plant breeders have used disease resistance genes (R genes) to control plant
      disease since the turn of the century. Molecular cloning of R genes that enable
      plants to resist a diverse range of pathogens has revealed that the proteins
      encoded by these genes have several features in common. These findings suggest
      that plants may have evolved common signal transduction mechanisms for the
      expression of resistance to a wide range of unrelated pathogens. Characterization
      of the molecular signals involved in pathogen recognition and of the molecular
      events that specify the expression of resistance may lead to novel strategies for
      plant disease control.

PMID- 7732375
TI  - The ethylene signal transduction pathway in plants.
AB  - Ethylene (C2H4), the chemically simplest plant hormone, is among the best
      characterized plant growth regulators. It participates in a variety of stress
      responses and developmental processes. Genetic studies in Arabidopsis have
      defined a number of genes in the ethylene signal transduction pathway. Isolation
      of two of these genes has revealed that plants sense this gas through a
      combination of proteins that resemble both prokaryotic and eukaryotic signaling
      proteins. Ethylene signaling components are likely conserved for responses as
      diverse as cell elongation, cell fate patterning in the root epidermis, and fruit
      ripening. Genetic manipulation of these genes will provide agriculture with new
      tools to prevent or modify ethylene responses in a variety of plants.

PMID- 7732376
TI  - Phytochromes: photosensory perception and signal transduction.
AB  - The phytochrome family of photoreceptors monitors the light environment and
      dictates patterns of gene expression that enable the plant to optimize growth and
      development in accordance with prevailing conditions. The enduring challenge is
      to define the biochemical mechanism of phytochrome action and to dissect the
      signaling circuitry by which the photoreceptor molecules relay sensory
      information to the genes they regulate. Evidence indicates that individual
      phytochromes have specialized photosensory functions. The amino-terminal domain
      of the molecule determines this photosensory specificity, whereas a short segment
      in the carboxyl-terminal domain is critical for signal transfer to downstream
      components. Heterotrimeric GTP-binding proteins, calcium-calmodulin, cyclic
      guanosine 5'-phosphate, and the COP-DET-FUS class of master regulators are
      implicated as signaling intermediates in phototransduction.

PMID- 7732377
TI  - Loss of atmosphere from Mars due to solar wind-induced sputtering.
AB  - Because Mars does not have a strong intrinsic magnetic field, the atmosphere is
      eroded by interactions with the solar wind. Early solar-system conditions
      enhanced the sputtering loss. It is calculated that approximately 3 bars of
      carbon dioxide (CO2) have been sputtered over the last 3.5 billion years. This
      significant increase over the previous estimate by Luhmann et al. of
      approximately 0.14 bar of CO2 is the result of the development of a more complete
      model. The model also predicts slightly greater loss of water--approximately 80
      meters instead of the approximately 50 meters predicted by Luhmann et al. Because
      estimates of CO2 on early Mars range from 0.5 to 5 bars, the 0.14-bar estimate is
      insignificant but the approximately 3-bar estimate will have a large effect on
      our understanding of the planet's evolution.

PMID- 7732378
TI  - Prebiotic synthesis of 5-substituted uracils: a bridge between the RNA world and
      the DNA-protein world.
AB  - Under prebiotic conditions, formaldehyde adds to uracil at the C-5 position to
      produce 5-hydroxymethyluracil with favorable rates and equilibria.
      Hydroxymethyluracil adds a variety of nucleophiles, such as ammonia, glycine,
      guanidine, hydrogen sulfide, hydrogen cyanide, imidazole, indole, and phenol, to
      give 5-substituted uracils with the side chains of most of the 20 amino acids in
      proteins. These reactions are sufficiently robust that, if uracil had been
      present on the primitive Earth, then these substituted uracils would also have
      been present. The ribozymes of the RNA world would have included many of the
      functional groups found in proteins today, and their catalytic activities may
      have been considerably greater than presently assumed.

PMID- 7732379
TI  - Oral immunization with a recombinant bacterial antigen produced in transgenic
      plants.
AB  - The binding subunit of Escherichia coli heat-labile enterotoxin (LT-B) is a
      highly active oral immunogen. Transgenic tobacco and potato plants were made with
      the use of genes encoding LT-B or an LT-B fusion protein with a microsomal
      retention sequence. The plants expressed the foreign peptides, both of which
      formed oligomers that bound the natural ligand. Mice immunized by gavage produced
      serum and gut mucosal anti-LT-B immunoglobulins that neutralized the enterotoxin
      in cell protection assays. Feeding mice fresh transgenic potato tubers also
      caused oral immunization.

PMID- 7732380
TI  - Generation and assembly of secretory antibodies in plants.
AB  - Four transgenic Nicotiana tabacum plants were generated that expressed a murine
      monoclonal antibody kappa chain, a hybrid immunoglobulin A-G heavy chain, a
      murine joining chain, and a rabbit secretory component, respectively. Successive
      sexual crosses between these plants and filial recombinants resulted in plants
      that expressed all four protein chains simultaneously. These chains were
      assembled into a functional, high molecular weight secretory immunoglobulin that
      recognized the native streptococcal antigen I/II cell surface adhesion molecule.
      In plants, single cells are able to assemble secretory antibodies, whereas two
      different cell types are required in mammals. Transgenic plants may be suitable
      for large-scale production of recombinant secretory immunoglobulin A for passive
      mucosal immunotherapy. Plant cells also possess the requisite mechanisms for
      assembly and expression of other complex recombinant protein molecules.

PMID- 7732381
TI  - Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding
      Ah receptor.
AB  - The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic and
      teratogenic effects of environmentally toxic chemicals such as dioxin. An AHR
      deficient (Ahr-/-) mouse line was constructed by homologous recombination in
      embryonic stem cells. Almost half of the mice died shortly after birth, whereas
      survivors reached maturity and were fertile. The Ahr-/- mice showed decreased
      accumulation of lymphocytes in the spleen and lymph nodes, but not in the thymus.
      The livers of Ahr-/- mice were reduced in size by 50 percent and showed bile duct
      fibrosis Ahr-/- mice were also nonresponsive with regard to dioxin-mediated
      induction of genes encoding enzymes that catalyze the metabolism of foreign
      compounds. Thus, the AHR plays an important role in the development of the liver
      and the immune system.

PMID- 7732382
TI  - Inhibition of proteasome activities and subunit-specific amino-terminal threonine
      modification by lactacystin.
AB  - Lactacystin is a Streptomyces metabolite that inhibits cell cycle progression and
      induces neurite outgrowth in a murine neuroblastoma cell line. Tritium-labeled
      lactacystin was used to identify the 20S proteasome as its specific cellular
      target. Three distinct peptidase activities of this enzyme complex (trypsin-like,
      chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing activities) were
      inhibited by lactacystin, the first two irreversibly and all at different rates.
      None of five other proteases were inhibited, and the ability of lactacystin
      analogs to inhibit cell cycle progression and induce neurite outgrowth correlated
      with their ability to inhibit the proteasome. Lactacystin appears to modify
      covalently the highly conserved amino-terminal threonine of the mammalian
      proteasome subunit X (also called MB1), a close homolog of the LMP7 proteasome
      subunit encoded by the major histocompatibility complex. This threonine residue
      may therefore have a catalytic role, and subunit X/MB1 may be a core component of
      an amino-terminal-threonine protease activity of the proteasome.

PMID- 7732383
TI  - Translational suppression by trinucleotide repeat expansion at FMR1.
AB  - Fragile X syndrome is the result of the unstable expansion of a trinucleotide
      repeat in the 5'-untranslated region of the FMR1 gene. Fibroblast subclones from
      a mildly affected patient, each containing stable FMR1 alleles with 57 to 285 CGG
      repeats, were shown to exhibit normal steady-state levels of FMR1 messenger RNA.
      However, FMR protein was markedly diminished from transcript with more than 200
      repeats. Such transcripts were associated with stalled 40S ribosomal subunits.
      These results suggest that a structural RNA transition beyond 200 repeats impedes
      the linear 40S migration along the 5'-untranslated region. This results in
      translational inhibition by trinucleotide repeat expansion.

PMID- 7732385
TI  - [Nursing. A reflection].

PMID- 7732384
TI  - Release of Ca2+ from individual plant vacuoles by both InsP3 and cyclic ADP
      ribose.
AB  - Calcium mobilization from intracellular pools couples many stimuli to responses
      in plant cells. Cyclic adenosine 5'-diphosphoribose (cADPR), which interacts with
      a ryanodine receptor in certain animal cells, was shown to elicit calcium release
      at the vacuolar membrane of beet storage root. The vacuolar calcium release
      pathway showed similarities to cADPR-gated calcium release in animal cells,
      including inhibition by ruthenium red, ryanodine activation, and high affinity
      for cADPR [Michaelis constant (Km) = 24 +/- 7 nanomolar]. Analysis by patch
      clamping demonstrated that the cADPR-gated pathway in beet is voltage-dependent
      over the physiological range, does not spontaneously desensitize, and is
      colocalized with an inositol 1,4,5-trisphosphate (InsP3)-gated calcium release
      pathway in individual vacuoles.

PMID- 7732386
TI  - [Administering aspirin and paracetamol to children].

PMID- 7732387
TI  - [MAQCEH. Method of evaluation of the quality of care in hospital nursing. A woman
      in labor].

PMID- 7732388
TI  - [Bone marrow transplantation. Time of reflection on intensive care and ethics].

PMID- 7732389
TI  - [Rehabilitation of the heart after myocardial infarct].

PMID- 7732390
TI  - [Care of the family after the death of a loved person].

PMID- 7732391
TI  - [Hopes and joys of a nurse. My viewpoint on nursing education].

PMID- 7732392
TI  - [There is no smoke without fire].

PMID- 7732393
TI  - [Conclusions from the psychiatric rehabilitation work at the Telhal Nursing
      Home].

PMID- 7732394
TI  - [Treatment and care of mental patients].

PMID- 7732395
TI  - [Organizing the caregiving: a function/challenge for the head nurse].

PMID- 7732396
TI  - [Nursing: the time and the method].

PMID- 7732397
TI  - [To validate the expressions of hospitalized children].

PMID- 7732398
TI  - [Methods of evaluation of the quality of care in hospital nursing].

PMID- 7732399
TI  - [The eyes and Alzheimer's disease].

PMID- 7732400
TI  - [Peripheral vascular disease. Is it arterial or venous?].

PMID- 7732401
TI  - [The Pope's message for the World Day of the Patient].

PMID- 7732402
TI  - [Nursing care in Kawasaki disease].

PMID- 7732403
TI  - [Role of the nurse in occupational health promotion].

PMID- 7732404
TI  - [Professional nursing].

PMID- 7732405
TI  - [The day hospital and the family].

PMID- 7732406
TI  - [Extracorporeal shockwave lithotripsy].

PMID- 7732407
TI  - [Alzheimer's disease as experienced by the family].

PMID- 7732408
TI  - [The nurse dealing with death].

PMID- 7732409
TI  - The medication minute: amphotericin B.

PMID- 7732410
TI  - Nursing research on urinary incontinence.

PMID- 7732411
TI  - Incontinence research studies: methodologic issues.

PMID- 7732412
TI  - Urinary tract infection rates among incontinent nursing home and community
      dwelling elderly.

PMID- 7732413
TI  - Basic elements of continence assessment.

PMID- 7732414
TI  - Basic elements of urodynamic evaluation in urinary incontinence.

PMID- 7732415
TI  - Basic elements of biofeedback therapy for pelvic muscle rehabilitation.

PMID- 7732416
TI  - Pelvic muscle exercises: physiotherapy for the pelvic floor.

PMID- 7732417
TI  - Indwelling catheters and devices: avoiding the problems.

PMID- 7732418
TI  - Clinical highlights: management of interstitial cystitis.

PMID- 7732419
TI  - Baggage in the bay?

PMID- 7732420
TI  - An observational study of prostaglandin E-1: comparing trial and maintenance
      dose.

PMID- 7732421
TI  - Psychosocial interventions for patients receiving hemodialysis.

PMID- 7732422
TI  - Assessment for biofeedback and behavioral therapy for urinary incontinence.

PMID- 7732423
TI  - Pediatric genitourinary trauma.

PMID- 7732424
TI  - Review of muscle physiology with application to pelvic muscle exercise.

PMID- 7732425
TI  - Hard-of-hearing or deaf: issues of ears, language, culture, and identity.
AB  - Most social work caseloads include some people who are deaf or hard-of-hearing,
      yet few social workers are attuned to the different and subtle ways in which
      hearing impairment can affect identity and relationships. People with hearing
      impairment make many self-defining choices--of communication method; language;
      and social, cultural, and political allegiance. Using information collected
      during a three-year research study of people with acquired hearing loss, this
      article defines and describes the complex and interrelated dimensions involved in
      assessing and serving people who are deaf or hearing impaired.

PMID- 7732426
TI  - Deaf and hard-of-hearing clients: some legal implications.
AB  - At least one of every 16 Americans has some degree of hearing loss and may use a
      variety of communication modes, including spoken English and American Sign
      Language. With the passage of various federal laws, most notably the Americans
      with Disabilities Act, social services agencies will need to become more aware of
      the needs of their deaf and hard-of-hearing clients. This article reviews federal
      legislation and statutes and their impact on service and legal programs.
      Legislative mandates for the use of assistive devices and interpreters in various
      settings are discussed. As service providers and advocates, social workers need
      to ensure that their own services adequately meet legal and ethical obligations
      and that the profession advocates for other agencies to do the same.

PMID- 7732427
TI  - Perceptions of social support and psychological adaptation to sexually acquired
      HIV among white and African American men.
AB  - Although the research literature documents the impact of social support on the
      mental health of people with human immunodeficiency virus (HIV) and acquired
      immune deficiency syndrome (AIDS), the assumption that relationships between
      social support and mental health functioning are comparable across ethnically
      distinct populations with HIV/AIDS has been challenged. This study reports
      preliminary data on the relationship between perceptions of social support and
      mental health in a sample of African American and white men with sexually
      acquired HIV. Data from 33 respondents revealed considerable differences within
      the sample. Data from white men revealed strong positive relationships between
      mental health measures and social support from friends and family, whereas data
      from African American men revealed negative relationships. Further, measures of
      social support seem to adequately reflect the support systems of white men but
      not those of African American men. Implications of these and additional findings
      for research and practice are considered.

PMID- 7732428
TI  - The Americans with Disabilities Act: implications for social services.
AB  - The Americans with Disabilities Act (ADA) of 1990 prohibits discrimination on the
      basis of disability in employment, state and local government services, public
      accommodations, and telecommunications. The act prohibits denying individuals
      with disabilities the opportunity to participate in a program or service or
      providing a service that is not equal to or that is different or separate from
      that given others. This article provides examples of possible barriers to full
      participation that might exist in social services and gives illustrations of
      reasonable modifications to increase access. Employers, private and government,
      profit and nonprofit, must make reasonable physical accommodations for disabled
      employees, unless such accommodation would cause undue hardship. This article
      gives examples of reasonable accommodations and undue hardship and discusses the
      ADA as a resource to clients with mental and physical disabilities and as a
      framework of protection for agencies serving them.

PMID- 7732429
TI  - Effects of psychosocial interactions at a cellular level.
AB  - Psychosocial interactions can affect physiological functions at a cellular level,
      resulting in increased longevity for people who have had heart attacks or who
      have acquired immune deficiency syndrome or cancer as well as for healthy
      individuals. Although social work pioneers and practitioners have always believed
      that social work intervention can help people feel better, recent studies show
      that the benefits can be measured quantitatively and qualitatively. In fact,
      these studies show that lack of psychosocial interaction may be a risk factor for
      disease progression.

PMID- 7732430
TI  - [Drugs ... What is the nurse's role?].

PMID- 7732431
TI  - [Nursing research. Evaluation of the quality of the information given to the
      patient].

PMID- 7732432
TI  - [To prescribe, distribute and inform. The role of the institution].

PMID- 7732433
TI  - [Perpetrator of many rapes, and murderer].

PMID- 7732434
TI  - [The grimacing woman].

PMID- 7732435
TI  - [Drug therapy of psychiatric disorders].

PMID- 7732436
TI  - [Mechanism of action of psychotropic agents].

PMID- 7732437
TI  - [Classification of psychotropic drugs. Practical aspects of their actual use].

PMID- 7732438
TI  - Prevention and treatment of nonsteroidal anti-inflammatory drug-induced
      gastropathy.
AB  - Numerous human studies have shown that the use of nonsteroidal anti-inflammatory
      drugs (NSAIDs) is associated with various gastroduodenal mucosal lesions,
      collectively referred to as NSAID gastropathy. NSAIDs should not be prescribed
      unless there is a clear-cut indication for them. Acetaminophen should be used
      initially to treat most patients with osteoarthritis. If NSAID therapy is
      required, the lowest possible NSAID dose should be prescribed, and the patient
      should be advised to reduce any modifiable risk factors. In patients who take
      NSAIDs occasionally and are at low risk for NSAID gastropathy, no specific
      prophylactic measures seem justified. In high-risk NSAID users, risk reduction
      and prophylaxis with misoprostol would be appropriate. If an ulcer is documented
      during NSAID treatment, NSAID therapy should be discontinued if possible.
      However, NSAID therapy need not be discontinued if it is therapeutically
      justifiable and if appropriate antiulcer treatment is initiated.

PMID- 7732439
TI  - Patterns of medication use in patients with heart failure: a report from the
      Registry of Studies of Left Ventricular Dysfunction (SOLVD).
AB  - To determine patterns of medication use based on clinical variables in patients
      with heart failure, we analyzed data from 5,999 patients participating in the
      Registry of Studies of Left Ventricular Dysfunction (SOLVD). The Registry
      comprised a broad spectrum of patients with heart failure, including some with
      predominantly diastolic dysfunction. Drug use was determined in a population
      cross-sectional manner at the time of identification (74% hospitalized). The
      median number of drugs per patient was four, with diuretics taken by 62%,
      digitalis by 45%, angiotensin-converting enzyme inhibitors (ACE-I) by 32%,
      calcium channel blockers by 36%, antiarrhythmics by 22%, and beta-blockers by
      18%. Only 18% were on the combination of ACE-I, diuretic, and digitalis.
      Stratification for diagnosis, heart failure symptoms, and ejection fractions
      demonstrated that triple-drug therapy (digitalis, diuretic, and ACE-I) was common
      only in those with ejection fractions less than .20 and several signs or symptoms
      of heart failure. Older patients were taking diuretics frequently (73% of
      patients older than 70 years of age), and our European center used fewer drugs
      overall, while prescribing digitalis about half as frequently as North American
      clinics. These data serve as the baseline for analysis of evolving therapeutic
      practice in patients with heart failure.

PMID- 7732440
TI  - Career satisfaction among psychiatrists in Texas.
AB  - We examined present and anticipated future levels of career satisfaction among
      psychiatrists in the greater Houston area. We gathered data by means of an
      anonymous questionnaire. The strongest univariate correlations between background
      variables and current and anticipated future levels of career satisfaction were
      found with age, years in practice, and source of professional income. Major
      threats to the quality of psychiatric practice were identified as changes in
      third-party reimbursement/managed care, competition from nonphysician mental
      health practitioners, and the national economy. Psychiatrists least satisfied
      with their current careers and most pessimistic about the future were found to be
      older with more years' experience and deriving their professional income chiefly
      from private practice. Much of their dissatisfaction appeared to relate to
      changes in third-party reimbursement/managed care and increasing competition from
      nonphysician mental health professionals.

PMID- 7732441
TI  - Vibrio vulnificus wound infections from the Mississippi Gulf coastal waters: June
      to August 1993.
AB  - Vibrio vulnificus, part of the normal marine flora of the Gulf of Mexico, is
      being increasingly recognized as an important human pathogen. V vulnificus
      contamination of superficial wounds can cause a severe, rapidly progressive,
      necrotizing cellulitis with bullous skin lesions that may require surgical
      debridement and is occasionally fatal. We summarize information about six cases
      of V vulnificus wound infection reported to the Mississippi State Department of
      Health from June to August 1993. Five of the six patients required
      hospitalization for intravenous antibiotic treatment and, in two cases, surgery.
      Two patients died from septicemia, despite aggressive antibiotic treatment; both
      had preexisting medical conditions that could have contributed to immune
      compromise and fulminant infection. This report underscores the virulence of this
      organism and the need for awareness by both the clinician and diagnostic
      laboratory personnel when dealing with superficial wounds occupationally or
      recreationally exposed to seawater.

PMID- 7732442
TI  - Reducing polypharmacy in extended care.
AB  - In this 5-year prospective study, we determined the feasibility of reducing
      polypharmacy in a long-term care institution by a systematic review of the
      pharmacy records. At 6-month intervals, the computer printout of all medications
      prescribed to patients in a 550-bed institution was reviewed. After patients
      taking more than 10 different drugs were identified, their physician was notified
      and was asked to review their medications according to specific guidelines. The
      number of patients taking 10 or more medications was reduced from 67, when the
      program was started, to 9. The average number of medications per patient was
      reduced from 5.5 to 4.6. This program reduced the prevalence of polypharmacy and
      had long-lasting effects on the physicians' prescribing habits. We also believe
      it led to improved patient care by reducing the potential for drug interactions
      and to cost savings for the pharmacy.

PMID- 7732443
TI  - Ileus following gynecologic surgery: management with water-soluble hyperosmolar
      radiocontrast material.
AB  - Postoperative ileus following gynecologic surgery can prolong hospitalization and
      may predispose patients to mechanical obstruction. Our objective was to study the
      safety and efficacy of a water-soluble, hyperosmolar, radiocontrast material in
      the management of postoperative ileus in patients having gynecologic surgery. Of
      115 cases, 57 were studied prospectively and received water-soluble radio-opaque
      contrast material via a nasogastric tube if bowel function had not returned by
      the third day. Fifty-eight well-matched control cases were managed without this
      material and received a suppository on the third day. The contrast material was
      well tolerated. Return of bowel function, day of oral intake, subsequent
      postoperative recovery, and duration of hospital stay were similar in the two
      groups. Water-soluble, hyperosmolar, radio-opaque contrast material given on the
      third postoperative day was safe, but of no apparent clinical benefit in
      resolving ileus following gynecologic surgery.

PMID- 7732444
TI  - CT-guided renal biopsy using a coaxial technique and an automated biopsy gun.
AB  - In this series, 35 patients with medical renal disease had renal biopsy guided by
      computed tomography (CT). Biopsies were done by a coaxial technique in which a
      thin-walled 16 guage guide needle is placed adjacent to the renal capsule of the
      lower pole. An 18 gauge cutting needle is then placed through the guide needle,
      and multiple samples (2 to 4) are obtained with an automated biopsy gun. Adequacy
      of specimens is immediately checked in the CT suite using low-power microscopy.
      Specimens are submitted for light, electron, and immunofluorescence microscopy.
      Adequate tissue for definite diagnosis was obtained in 33 of the 35 patients
      (94%). One patient had moderate postbiopsy bleeding and was hospitalized. There
      were no major complications. CT-guided renal biopsy using a coaxial technique and
      automated biopsy gun is an effective means of obtaining tissue for the evaluation
      of medical renal disease.

PMID- 7732445
TI  - Long-term failure of pelvic floor musculature exercises in treatment of genuine
      stress incontinence.
AB  - This report evaluates the motivation of a group of patients to continue a program
      of pelvic floor musculature exercises as conservative therapy for genuine stress
      incontinence. Fourteen women with urodynamically documented genuine stress
      incontinence had subjective improvement; nine of them showed objective
      improvement after 4 weeks of supervised pelvic floor musculature exercises. These
      patients were questioned 5 years later as to continence status, performance of
      pelvic floor musculature exercises, and subsequent surgery for incontinence. Ten
      of 14 patients responded: four have had anti-incontinence surgery and remain
      continent; five have not had surgery, do not perform pelvic floor musculature
      exercises, and continue to have stress incontinence. One patient continues to
      perform pelvic floor musculature exercises and has stress incontinence with a
      full bladder. Thus, only one patient out of 10 remained sufficiently motivated to
      perform pelvic floor musculature exercises after 5 years, even though all
      patients in this series had improvement after a 4-week course of supervised
      exercises.

PMID- 7732446
TI  - Health hazards among working children in Texas.
AB  - This report represents the first attempt to assemble existing data from a variety
      of sources regarding children less than 18 years of age in the work force in
      Texas. These data include the frequency of detected violations of child labor
      laws, reports of injuries to the Texas Workers' Compensation Commission, and work
      related deaths as ascertained from death certificates. More than 1,000 minors
      were detected as being illegally employed in Texas each year since 1986 and
      nearly 1,100 work-related injuries in children 18 years of age and younger were
      reported to the Texas Workers' Compensation Commission in 1991. A review of Texas
      death certificates from 1980 to 1990 revealed 125 work-related fatalities among
      children. The leading cause of death was motor vehicle injuries, followed by
      injuries from machinery (usually agricultural machinery). The magnitude and
      severity of occupational illnesses in working children are unknown. Because of
      physiologic differences in size, metabolism, and absorption, children may be
      especially susceptible to work-related injury and illness. Health and safety data
      on working children in Texas, as in most other places, are fragmented and
      incomplete. These data are needed to identify children at high risk of injuries
      and illnesses, to target prevention programs, and to identify areas for
      additional legislation. More rigorous enforcement of current legislation is also
      needed.

PMID- 7732447
TI  - Results of laparoscopic versus open cholecystectomy in a community hospital.
AB  - In a retrospective study, the first 301 patients who had laparoscopic
      cholecystectomy (LC) in a university-affiliated community hospital were compared
      with a historical matched control group of patients who had open cholecystectomy.
      The patients who had LC had a shorter hospital stay, required less postoperative
      pain medication, resumed normal activities and returned to work sooner, and had a
      lower minor and total complication rate. The mean operating time was 45 minutes
      longer for LC. Major complications, common bile duct injuries, and mortality were
      similar in both patient groups. The learning curve, use of laser, and use of
      cholangiography were all analyzed. Our results with LC compared favorably with
      results reported in the medical literature.

PMID- 7732448
TI  - Colonoscopic follow-up of adenomas and colorectal cancer.
AB  - Increasing experience with colonoscopy has altered recommendations for the
      frequency of follow-up surveillance examinations for adenomatous polyps and
      colorectal cancer. Current recommendations include a follow-up colonoscopy at 1
      year for patients with more than two adenomatous or highly suggestive polyps and
      after curative surgery for colorectal cancer. Other patients can safely receive a
      follow-up colonoscopy at longer intervals of 3 years. Published data and a review
      of the Ochsner Clinic experience are presented to support these recommendations.

PMID- 7732449
TI  - Expanding the envelope of neonatal endoscopic tracheal and bronchial surgery.
AB  - Diagnostic evaluation of the neonatal airway requires special training and
      instrumentation. The subglottis of a normal full-term infant will allow passage
      of a 3.0 bronchoscope (outer diameter 5.0 mm, inner diameter 4.3 mm). On
      occasion, diagnostic rigid endoscopy with simultaneous ventilation in premature
      infants necessitates use of a 2.5 bronchoscope (outer diameter 4.2 mm, inner
      diameter 3.5 mm). Although flexible bronchoscopy can be done through an
      endotracheal tube, surgical manipulation of the airway is limited. Rigid
      pediatric bronchoscopic optical forceps are too large for use in neonatal
      bronchoscopes. Therefore, performance of endoscopic tracheal and bronchial
      procedures in the premature infant requires innovative techniques with thorough
      knowledge of instrumentation and anesthetic management, generally including
      apneic techniques. As advances in neonatology result in survival of smaller and
      smaller patients, otolaryngologists must keep pace to provide adequate support. A
      case report of endoscopic removal of a granuloma totally obstructing the right
      primary bronchus in a 1 kg premature infant illustrates these concepts in
      neonatal endoscopy.

PMID- 7732450
TI  - Perforated solitary jejunal diverticulum.
AB  - We report a case of perforated solitary jejunal diverticulum in an 80-year-old
      woman. Jejunal diverticulosis occurs in 0.07% to 2.0% of the population. Jejunal
      diverticulitis with perforation is rare and is associated with high mortality.
      Treatment is surgical resection of the involved segment. Several theories to
      explain the pathogenesis of jejunal diverticula may relate to manometric or
      histologic abnormalities of the small bowel.

PMID- 7732451
TI  - Epinephrine-induced lactic acidosis in the setting of status asthmaticus.
AB  - A relationship between intravenous epinephrine infusion and the development of
      lactic acidosis has been well described. We report a temporal association between
      the administration of subcutaneous epinephrine and the development of lactic
      acidosis in the setting of status asthmaticus. A 20-year-old woman with a history
      of asthma came to the emergency service in acute respiratory distress and was
      treated with subcutaneous epinephrine. Six hours later, serial arterial blood gas
      studies revealed the onset of a primary metabolic acidosis. Additional diagnostic
      studies revealed a serum lactate level of 9.5 mumol/L. The lactic acidosis
      resolved within 15 hours. The patient never exhibited signs of hypotension,
      hypoxemia, or sepsis, and other potential etiologies for lactic acidosis were
      excluded. We believe the events of this case constitute a new observation and
      theorize a mechanism of peripheral vasoconstriction and transient tissue
      hypoperfusion mediated by the subcutaneous epinephrine.

PMID- 7732452
TI  - Acute epidural hematoma of the cervical spine: an unusual cause of neck pain.
AB  - Cervical spinal epidural hematoma is an unusual neurosurgical disorder that
      usually requires emergent surgical decompressive therapy. We report the case of
      an 85-year-old woman with acute, severe neck and shoulder pain with progressive
      neurologic deficits. A computed tomography scan of the neck revealed an acute
      cervical spinal epidural hematoma. This case involves an unusual cause of neck
      pain in an elderly patient with no history of trauma. It is incumbent on the
      emergency physician to recognize this disorder and arrange emergent neurosurgical
      consultation to ensure an optimal outcome. Further, the differential diagnosis of
      neck pain and progressive neurologic findings should include this entity.

PMID- 7732453
TI  - Primary small bowel lymphoma manifested as obstructive jaundice in a patient with
      AIDS.
AB  - We describe a patient with acquired immunodeficiency syndrome (AIDS) and non
      Hodgkin's lymphoma of the duodenum manifested as obstructive jaundice. Endoscopic
      retrograde cholangiography led to the diagnosis and was used to relieve the
      obstruction. The patient received chemotherapy and is in remission 21 months
      after the diagnosis, thus justifying an aggressive approach toward diagnosis and
      treatment in this patient population.

PMID- 7732454
TI  - Pneumonia due to Staphylococcus aureus in a patient with AIDS: review of
      incidence and report of an atypical roentgenographic presentation.
AB  - Multiple defects in host defense mechanisms produce an increased incidence of
      community-acquired bacterial pneumonia in individuals infected with the human
      immunodeficiency virus. Clinical studies suggest that Staphylococcus aureus is an
      uncommon cause of such infections, though its incidence is increased in the
      setting of intravenous drug use, indwelling vascular catheter, and coexistent
      pulmonary Kaposi's sarcoma or pneumonia due to Pneumocystis carinii. The
      significantly higher incidence of S aureus pneumonia documented in autopsy series
      suggests that the infection frequently remains undiagnosed ante mortem. The
      clinical and radiologic presentation of staphylococcal pneumonia in HIV
      seropositive patients is similar to that seen in immunocompetent hosts. However,
      atypical radiographic patterns can occur. We describe a case of S aureus
      pneumonia manifested as an infiltrate with focal predominance and multiple
      cavitary lesions. Such a radiologic appearance has not previously been described
      in this population. Given the likelihood that pneumonia due to S aureus is
      significantly underdiagnosed ante mortem, a high index of clinical suspicion is
      warranted.

PMID- 7732455
TI  - Sarcoid myopathy in a patient with human immunodeficiency virus infection.
AB  - Although neither sarcoidosis nor HIV infection is rare, only eight patients with
      both diseases have been described. None of the eight had sarcoid myopathy. We
      describe a patient who had HIV infection and decreased CD4+ T-lymphocytes as well
      as sarcoidosis with muscle involvement. During 3 years of observation, primary
      sarcoidosis remitted and myopathic symptoms were controlled with prednisone. No
      opportunistic infections occurred during more than 3 years of prednisone therapy.

PMID- 7732456
TI  - Sinful saints or saintly sinners?

PMID- 7732457
TI  - Yesterday's research: today's standards.

PMID- 7732458
TI  - Spontaneous rupture of low transverse cesarean scar.

PMID- 7732459
TI  - New technology: costly? Or cost-effective?

PMID- 7732460
TI  - Attitudes of southern adolescents toward smoking.

PMID- 7732461
TI  - Beer potomania.

PMID- 7732462
TI  - Morphology of the second cervical vertebra and the posterior projection of the C2
      pedicle axis.
AB  - STUDY DESIGN: This study assessed numerous structural features of the second
      cervical vertebra (C2), describing the projection point of the pedicle on its
      posterior aspect. OBJECTIVES: Evaluation of the specimens included quantitative
      description of 18 linear and four angular parameters, which then were correlated
      between male and female specimens. The point of projection of the C2 pedicle axis
      was described with an emphasis on a perspective relevant to a posterior approach.
      SUMMARY OF BACKGROUND DATA: The literature regarding the anatomy of the axis
      focuses mainly on the dens. Very little research regarding the quantitative study
      of the C2 pedicle has been reported. METHODS: Fifty dry C2 cervical vertebrae (30
      male, 20 female) were obtained for anatomic measurements. Anatomic evaluation
      focused on the pedicle, vertebral body, dens, superior facet, and vertebral
      canal. All measurements were made using calipers and a standard rule linear
      measurements and a goniometer for angular measures. Based on the measurement of
      50 specimens, including 18 linear and four angular parameters, the mean, range,
      and standard deviation were calculated for all of the specimens and for male and
      female separately. RESULTS: A significant difference was found to exist for 11 of
      18 linear measurements and one of four angular parameters. The projection point
      of the pedicle axis on the posterior aspect of the lateral mass was described
      with an emphasis on a perspective relevant to a posterior surgical approach. The
      location of the projection point of the pedicle axis was found to be 5.4 +/- 1.2
      mm inferior to the horizontal line, and 7.2 +/- 1.3 mm lateral to the vertical
      line. The pedicle axis was found to lie at 33 degrees in the medial direction and
      20 degrees in the superior direction form the point of pedicle axis projection.
      CONCLUSIONS: When the techniques described here are used, the findings may be
      helpful in cases involving C2 when surgical intervention and instrumentation are
      desired.

PMID- 7732463
TI  - Computed tomographic evaluation of the normal adult odontoid. Implications for
      internal fixation.
AB  - STUDY DESIGN: Computed tomography scans of the dens were performed on patients
      who had no atlantoaxial pathology. OBJECTIVES: To determine whether one or two
      screws is optimal for fracture fixation and whether two screws can always
      negotiate the intramedullary odontoid cavity. SUMMARY OF BACKGROUND DATA:
      Fixation of Type II dens fractures traditionally has used C1-C2 posterior wiring
      and fusion. Two screws placed across an odontoid fracture as a method of rigid
      internal fixation also has been described. However, it is not known whether two
      screws can always negotiate the odontoid canal. METHODS: Ninety-two consecutive
      computerized tomography scans of the dens were performed on adults who had no
      atlantoaxial pathology. Measurements were taken from the scan and compared with
      the cross-sectional diameter of two odontoid screws. RESULTS: The critical
      diameter for the placement of two 3.5-mm cortical screws with tapping was 9.0 mm.
      This dimension was present in 95% of the patients studied. CONCLUSIONS: Correct
      orientation of the computerized tomography scanner is critical for accurate
      measurements. Two 3.5-mm screws can be used in internal fixation of Type II dens
      fractures in 95% of the patients if the inner cortex is tapped.

PMID- 7732464
TI  - Relationship between evoked potentials and clinical status in spinal cord
      ischemia.
AB  - STUDY DESIGN AND METHODS: Sciatic neurogenic motor-evoked potentials, spinal
      evoked potentials, and somatosensory-evoked potentials were recorded in 12
      anesthetized dogs that had arterial ischemia of the lumbar cord produced by
      ligation of segmental arteries. The presence or absence of the above-mentioned
      potentials was compared with the clinical status of repeated wake-up tests.
      RESULTS: Although these results were complicated, sciatic neurogenic motor-evoked
      potential was more sensitive to the spinal cord ischemia and was a better
      predictor of clinical outcome than spinal evoked potential and somatosensory
      evoked potential. However, the presence was not a guarantee of normal function.
      The initial morphologic change of these potentials secondary to ischemia
      consisted of a decrease in amplitude and in the number of peaks without a shift
      of latency. CONCLUSIONS: The present study suggests that the peripheral
      neurogenic motor-evoked potential is a better warning system for spinal cord
      ischemia and that its adoption may contribute to the prevention of cord ischemia
      during spinal surgery, whereas somatosensory-evoked potential and spinal evoked
      potential cannot be indices.

PMID- 7732465
TI  - Ultrastructural observations on the ossification of the supraspinous ligament.
AB  - STUDY DESIGN: This study analyzed the process of ossification of spinal
      ligaments. Supraspinous ligaments excised during surgery were studied by light
      and scanning electron microscopy. OBJECTIVES: The results were correlated to
      determine the mechanism of ossification of spinal ligaments. SUMMARY OF
      BACKGROUND DATA: Ossification of the ligamentum flavum has been described in
      detail by Hiraoka, Yamaguchi, and others. However, the pathogenesis of
      ossification of the spinal ligaments remains unclear. Some studies have been
      performed by light and transmission electron microscopy, but no detailed
      investigation of the ossification of the spinal ligaments by scanning electron
      microscopy has been performed. METHODS: Specimens of supraspinous ligament were
      taken from 41 patients during spinal surgery. Ossification was diagnosed
      macroscopically and radiologically for 20 patients. The specimens were examined
      using light and scanning electron microscopy. RESULTS: Collagen fibrils were 700
      2000 A in diameter and were arranged in parallel. The ligament insertion divided
      into four zones and seemed to fit the description of Enthesis histologically.
      Close to the ossification region, there were a region in which some fibrils were
      thinner and branchings became slightly stronger, tending to form bridges of
      minute fibrils between other fibrils. Closer to the region of actual
      ossification, there was a region in which extra-fibrillar substances completely
      deposited. In the region of actual ossification, there were medullary spaces of
      varying sizes, and the surrounding collagen fibers were dense and arranged in a
      lamellar fashion. Osteocyte lacunae had formed and the cells regarded to be the
      osteocytes were present on the inside. CONCLUSION: Ossification of the
      supraspinous ligament possibly occurs as follows. Fibroblasts or chondrocyte-like
      cells respond to some external stimulus, form an irregular network of fine
      fibrils, and produce acid mucopolysaccharide. These undergo calcification and
      capillary invasion. Undifferentiated mesenchymal cells invaded and are
      transformed into osteoblasts. Then osteogenesis ensues with progressive
      calcification.

PMID- 7732466
TI  - Increased femoral neck-shaft angles in adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Ninety-four females from Southern China, 61 with adolescent
      idiopathic scoliosis and 33 normal subjects, were evaluated for femoral neck
      shaft angles and associated asymmetry between the hips. For statistical analysis,
      the groups were divided into adolescent and adult, and the scoliosis group was
      further divided into sub-groups according to the type of spinal curvature.
      OBJECTIVES: To evaluate femoral neck-shaft angle and asymmetry between the hips,
      and their relation to adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND
      DATA: Recently published studies have suggested there is an association between
      asymmetry of the hip and lower limb and the curvature in AIS. In this study,
      femoral neck-shaft angle in patients with adolescent idiopathic scoliosis and in
      normal subjects was evaluated. METHODS: Femoral neck-shaft angles of both hips
      and lateral spinal curvature (using Cobb's method) were measured from standard
      standing anteroposterior radiographs of the pelvis, including upper femora and
      spine. Methods of measuring femoral neck-shaft angles were evaluated in an intra-
      and inter-observer study and were found to be accurate. RESULTS: Patients with
      scoliosis had highly significantly greater femoral neck-shaft angles of both hips
      compared with normal subjects. In normal subjects, the femoral neck-shaft angle
      difference between the hips (asymmetry) was not statistically significant. This
      asymmetry in the scoliosis group also was not statistically significant when the
      results were analyzed upon grouping them all together, irrespective of curve
      pattern. CONCLUSION: Our new findings show that patients with scoliosis have
      abnormally increased femoral neck-shaft angles, and the asymmetry is
      characteristic and significantly different from that of normal subjects.
      Moreover, increased femoral neck-shaft angle is related to type and side of
      spinal curvature.

PMID- 7732467
TI  - Care-seeking among individuals with chronic low back pain.
AB  - STUDY DESIGN: This was a stratified, random telephone survey of adults in North
      Carolina. OBJECTIVE: To determine the prevalence of chronic low back pain and the
      extent to which treatment is sought for this condition. SUMMARY OF BACKGROUND
      DATA: Chronic low back pain is a major problem. Previous studies often have
      combined acute and chronic back pain. METHODS: Telephone interviews regarding
      back pain were conducted with 4437 North Carolina adults during 1992. RESULTS:
      Chronic back pain affects 3.9% of the North Carolina population. Thirty-four
      percent considered themselves permanently disabled and 52% assessed their overall
      health as fair or poor. The median number of bed-disability days per year was
      three. Seventy-three percent saw a health care provider. Of those who sought
      care, 91% saw a medical doctor, 29% saw a physical therapist, and 25% saw a
      chiropractor. Use of technology was extensive: 37% received a computed tomography
      scan, 25% received a magnetic resonance imaging scan, and 10.4% underwent
      surgery. CONCLUSIONS: Chronic back pain is common, and the level of care-seeking
      and costs of care among those afflicted are extremely high.

PMID- 7732468
TI  - On the accuracy of history, physical examination, and erythrocyte sedimentation
      rate in diagnosing low back pain in general practice. A criteria-based review of
      the literature.
AB  - STUDY DESIGN: A criteria-based review of the literature was conducted regarding
      the accuracy of history, physical examination, and erythrocyte sedimentation rate
      in diagnosing low back pain. OBJECTIVES: To perform meta-analysis of the
      literature regarding signs and symptoms in diagnosing radiculopathy, ankylosing
      spondylitis, and vertebral cancer. SUMMARY OF BACKGROUND DATA: Diagnosing low
      back pain, especially in general practice, depends largely on history taking,
      physical examination, and the erythrocyte sedimentation rate. No previous review
      has assessed the diagnostic accuracy of signs and symptoms in a systematic way,
      taking into account the methodological quality of studies. METHODS: The
      literature was reviewed for relevant studies. Retrieved studies were
      independently rated for methodological quality by two reviewers. The reported
      sensitivity and specificity in the rated studies were reviewed. RESULTS: Thirty
      six eligible studies were retrieved. Major methodological shortcomings were
      observed, and only 19 studies scored > or = 55 points (maximal score 100). Not
      one single test appeared to have high sensitivity and high specificity in
      radiculopathy. The combined history and the erythrocyte sedimentation rate had
      relatively high diagnostic accuracy in vertebral cancer. Getting out of bed at
      night and reduced lateral mobility seemed to be the only moderately accurate
      items in ankylosing spondylitis. CONCLUSIONS: Additional studies that take into
      account the shortcomings identified would be needed to produce definite
      conclusions. Few of the studied signs and symptoms seemed to be valuable
      diagnostics for radiculopathy, ankylosing spondylitis, and vertebral cancer.
      Reproducibility of signs and symptoms over time might be a valuable diagnostic
      criterion. However, this was neglected in almost all studies.

PMID- 7732469
TI  - "Cross-sectional" study of low back pain among workers at an industrial
      enterprise in Russia.
AB  - STUDY DESIGN: A representative sample of 18- to 65-year-old workers from a
      machine-building factory was studied using a standardized questionnaire.
      OBJECTIVES: To study the prevalence of low back pain syndrome among workers at an
      industrial enterprise and to estimate the association between low back pain
      syndrome and certain factors. METHODS: This was a cross-sectional study of 800
      workers (400 men and 400 women), who were invited to participate in the study.
      Seven-hundred-and-one (87.6%) persons took part in the study--339 (84.7%) men and
      362 (90.5%) women. RESULTS: The life-time prevalence of low back pain complaints
      was 48.2%. The prevalence during the last year was 31.5%, and point prevalence
      was 11.5%. The number of patients with low back pain complaints increased with
      age. The duration of a low back pain episode was less than 2 weeks in 88.2% of
      the patients, and more than 12 weeks in only in 1.8% of the patients. Analysis of
      some social, individual, and professional factors revealed associations between
      low back pain and low level of education, marital status, absence of sports
      activity, intensity of smoking, and frequent lifting and bending during the work
      day. CONCLUSION: Our study revealed a high prevalence of low back pain among
      workers at an industrial enterprise. This low back pain was primarily of an acute
      nature.

PMID- 7732470
TI  - Effect of intensive training on the isokinetic strength and structure of lumbar
      muscles in patients with chronic low back pain.
AB  - STUDY DESIGN: This study investigated the effects of the intensive physical
      rehabilitation program on the trunk and knee extensor muscles in patients with
      chronic low back pain. At baseline and after 3 months, strength was measured and
      muscle biopsies were taken. OBJECTIVES: To evaluate the effects of strength
      exercises on the structure of back muscles. SUMMARY OF BACKGROUND DATA:
      Rehabilitation designed for chronic low back pain patients improves trunk muscle
      strength, mobility of the spine, and the patients' functional capacity. The
      effects of such programs on the structure of back muscles have not been reported
      previously. METHODS: Thirty patients with chronic low back pain volunteered to
      participate in the study. Biopsies were taken from the multifidus and vastus
      lateralis muscles. The sizes of Types 1 and 2 muscle fibers were measured. The
      peak-torques of isokinetic trunk and knee extension were determined at two
      different angular velocities. RESULTS: Strength increased by 19-22% (P < 0.05) in
      trunk extension and by 7-11% (P < 0.05) in knee extension. Type 1 fibers
      maintained their pre-exercise size. The size of Type 2 muscle fibers in men
      increased by 11% (P < 0.05) in the multifidus and by 8% (P < 0.05) in the vastus
      lateralis. In women, the corresponding increases were 11% (P = 0.16) and 11% (P <
      0.05). The correlation between the size of Type 2 muscle fibers in the multifidus
      and the strength of trunk extension improved, especially in men at follow-up.
      CONCLUSIONS: The results of the present study suggest that training with maximal
      or submaximal effort may reverse the selective atrophy of Type 2 fibers in the
      multifidus muscles in men. Intensive training also can significantly increase the
      trunk extension strength in women, but women may need a longer training period
      than men to achieve significant structural changes in their back muscles.

PMID- 7732471
TI  - The Quebec Back Pain Disability Scale. Measurement properties.
AB  - STUDY DESIGN: The Quebec Back Pain Disability Scale is a 20-item self
      administered instrument designed to assess the level of functional disability in
      individuals with back pain. The scale was administered as part of a larger
      questionnaire to a group of 242 back pain patients. Follow-up data were obtained
      after several days and after 2 to 6 months. OBJECTIVES: The goal of this study
      was to determine whether the Quebec scale is a reliable, valid, and responsive
      measure of disability in back pain, and to compare it with other disability
      scales. SUMMARY OF BACKGROUND DATA: A number of functional disability scales for
      back pain are being used, but their conceptual validity is uncertain. Unlike most
      published instruments, the Quebec scale was constructed using a conceptual
      approach to disability assessment and empirical methods of item development,
      analysis, and selection. METHODS: The authors calculated test-retest and internal
      consistency coefficients, evaluated construct validity of the scale, and tested
      its responsiveness against a global index of change. Direct comparisons with the
      Roland, Oswestry, and SF-36 scales were carried out. RESULTS: Test-retest
      reliability was 0.92, and Cronbach's alpha coefficient was 0.96. The scale
      correlated as expected with other measures of disability, pain, medical history,
      and utilization variables, work-related variables, and socio-demographic
      characteristics. Significant changes in disability over time, and differences in
      change scores between patients that were expected to differ in the direction of
      change, were found. CONCLUSIONS: The Quebec scale can be recommended as an
      outcome measure in clinical trials, and for monitoring the progress of individual
      patients participating in treatment or rehabilitation programs.

PMID- 7732472
TI  - Outpatient conventional laminotomy and disc excision.
AB  - STUDY DESIGN: This study analyzes the clinical records of 75 consecutive cases of
      outpatient disc excision performed by the author on a prospective basis.
      OBJECTIVES: The results were analyzed to determine the practicality of performing
      conventional outpatient laminotomy on an outpatient basis. SUMMARY OF BACKGROUND
      DATA: Outpatient disc excision has not been reported in the literature. Current
      awareness of the cost constraints of medical practice and the options of other
      outpatient disc procedures, such as microdiscectomy and percutaneous discectomy,
      make this a timely subject for analysis. METHODS: The clinical data were
      collected prospectively on 75 consecutive patients operated on as outpatients by
      the author. RESULTS: No complications or problems were experienced in the
      performance of this procedure in the outpatient setting. Two complications that
      did occur were neither due to the outpatient setting nor influenced in any way by
      the outpatient setting. CONCLUSIONS: Outpatient surgery is a practical
      alternative for selected patients requiring disc surgery.

PMID- 7732473
TI  - Chronic disabling low back pain syndrome caused by internal disc derangements.
      The results of disc excision and posterior lumbar interbody fusion.
AB  - STUDY DESIGN: This study reviewed 62 consecutive patients with chronic disabling
      low back pain who were treated with disc excision and posterior lumbar interbody
      fusion. Outcomes of treatment results were evaluated by a follow-up evaluation.
      OBJECTIVE: To evaluate the efficacy of the surgical treatment of patients with
      chronic disabling low back pain resulting from internal disc derangements that
      does not respond to nonoperative treatments. SUMMARY OF BACKGROUND DATA: Chronic
      and disabling low back pain that persists for more than 6 months and does not
      respond to all known modalities of nonoperative treatment represents a difficult
      problem. No sufficient information exists in the literature regarding the
      efficacy of any specific treatment method for this group of patients. METHODS:
      During a 7-year period between 1984 and 1990, 62 consecutive patients were
      treated with disc excision and posterior lumbar interbody fusion. The clinical
      outcomes were evaluated by postoperative follow-up questionnaire, and the fusion
      result was evaluated by x-ray studies of the lumbosacral spine. RESULTS:
      Approximately 87% of the 62 patients responded properly to the follow-up
      evaluation. Eighty-nine percent of the patients had satisfactory results, 93%
      returned to work, and a successful fusion was obtained in 94% of the patients.

PMID- 7732474
TI  - Traumatic lumbosacral dislocation in a 5-year-old boy with eight years follow-up.
AB  - STUDY DESIGN: The authors present an unusual case of pure traumatic bilateral
      lumbosacral dislocation in a 5-year-old boy, the conservative treatment carried
      out, and the long-term result. OBJECTIVES: To describe a rare traumatic lesion in
      children and evaluate the result obtained with conservative treatment. SUMMARY OF
      BACKGROUND DATA: Watson-Jones was the first to describe this type of lesion.
      Since then, only a few cases have been added. Most authors suggest that open
      reduction should be carried out. No cases of this type of injury in children have
      been reported. METHODS: A 5-year-old boy was hit in the lumbosacral region with a
      rocking chair. Examination showed neurologic deficit of left L5 and S1 nerve
      roots. Roentgenographic examination and computed tomography scan confirmed the
      anterior dislocation of the fifth lumbar vertebra on the sacrum without any
      fracture. He was treated with traction, followed by hyperextension in a Cotrel
      traction table and further immobilization with a lumbar plaster jacket. RESULTS:
      Eight years after the injury, the patient had no neurologic deficit and lumbar
      radiographs showed a good alignment of the lumbosacral spine. CONCLUSION: In
      children with traumatic lumbosacral dislocation, closed reduction should be
      attempted even if neurologic deficit is present.

PMID- 7732475
TI  - Metastatic paraganglioma causing spinal cord compression.
AB  - SUMMARY OF BACKGROUND DATA: Paragangliomas are neoplasms that arise from the
      autonomic nervous system-associated paraganglia. Most often they are benign
      tumors. However, infrequently they have been reported to metastasize. Involvement
      of the spine is rare and usually is intradural at the level of the cauda equina.
      OBJECTIVES: The authors report two cases of metastatic paraganglioma to the
      spine, both of which resulted in myelopathy from extradural spinal cord
      compression. Also provided is a review of the literature. CONCLUSIONS:
      Paragangliomas rarely metastasize to the spine. Management of the two reported
      patients involved spinal cord decompression followed by spinal stabilization
      procedures. Long-term ambulatory status was maintained in both patients.
      Radiation therapy may be an important adjunctive treatment after surgical removal
      of these tumors.

PMID- 7732476
TI  - Multiple psoas abscesses after posterior spinal fusion.
AB  - STUDY DESIGN: A case of multiple psoas abscesses after Dove lumbar spine fixation
      is reported. OBJECTIVES: To review the diagnosis and treatment of deep infection
      after internal spinal fixation. METHODS: The possibility of septic complications
      after spinal surgery that may present with a degenerative pattern is examined.
      The clinical and computed tomographic findings of a psoas abscess are recalled.
      RESULTS: Surgical drainage of the purulent collection was performed along with
      prolonged parenteral antibiotic treatment. CONCLUSION: Infection should be
      considered as a cause of recurrence of pain after internal fixation of the lumbar
      spine.

PMID- 7732477
TI  - Nonoperative treatment for low back pain. Rest to restoration.
AB  - Pain and disability due to disorders of the lumbar spine are endemic in
      industrialized society. Nonoperative management of low back pain syndromes is
      most often successful but is complicated by myriad of unproven treatment options.
      Recent studies have shown that the natural history favors recovery regardless of
      the type of treatment. With increasing time from onset of symptoms, therapeutic
      interventions shift from rest and applied therapies to exercise and physical
      restoration. This also requires an evolution from passive to active participation
      by the patient. This article outlines current trends and recommendations for the
      application of various nonoperative treatment methods as low back pain persists
      through time.

PMID- 7732478
TI  - Coccyx. The bone named for a bird.

PMID- 7732479
TI  - Pro: outcomes research is cost effective and critical to the specialty.

PMID- 7732480
TI  - Con: some clinical research is not cost-effective--weaknesses of outcome studies.

PMID- 7732481
TI  - Spinal nomenclature.
AB  - There has been a proliferation of differing terms, even among practicing
      surgeons. A morphologically based nomenclature may be needed for radiologic
      purposes, whereas a more histopathologic terminology would be desirable for
      surgical descriptors. Whichever approach is undertaken, the true radiologic
      surgical correlation of disc abnormalities within the spine is doomed to failure
      without agreement on some type of standard nomenclature. A review of the problem
      and potential solutions are suggested.

PMID- 7732482
TI  - [Amyloidosis of the small intestine secondary to rheumatoid arthritis and
      juvenile rheumatoid arthritis: report of two cases].
AB  - We herein report two cases of gastrointestinal amyloidosis, secondary to juvenile
      rheumatoid arthritis (JRA) in one, and rheumatoid arthritis (RA) in the other. A
      21-year-old woman, who has been suffering from JRA for the past 12 years, was
      transferred to our hospital due to intense pain in the epigastrium and back,
      diarrhea, high fever, and paralytic ileus. Treatment by corticosteroid,
      antibiotics, protease inhibitor, and total parenteral nutrition was not
      effective. The laparoscopic surgery was performed because of repeated melena
      followed by an episode of hypovolemic shock. The resected specimen of the ileum
      showed histologically marked amyloid deposition in the arteriolar walls. A 83
      year-old man with RA for 14 years, was admitted to our hospital with complaints
      of abdominal pain, nausea, and diarrhea. He underwent an emergency operation for
      perforation of the ileum. The resected specimen revealed amyloid deposition and
      non-caseating granulomas. The fragility and impaired blood supply caused by
      amyloid deposition in the vascular walls may have terminated in the severe
      intestinal lesion. Further clinicopathological studies along this line are keenly
      desired in order to establish therapeutic modalities for gastrointestinal
      amyloidosis.

PMID- 7732483
TI  - [Ataxic sensory and autonomic neuropathies associated with primary Sjogren's
      syndrome: a case report].
AB  - A 49-year-old woman had xerostomia and foreign body sensation of eye since 27
      years old. Since the age of 30 she developed occasional fever attack released by
      cooling body without medication. Three years later she began to complain
      difficulty to maintain standing position with closed eyes. Upon admission
      axillary lymph node swelling, anisocoria and Adie's pupils were evident. She had
      reddish and atrophic dry tongue. Peripheral reflexes of upper extremities were
      decreased. Patellar and achilles tendon reflexes were diminished. Perception of
      pain and temperature were reduced on the right peripheral upper and lateral lower
      extremities. Deep sensation of four extremities were also decreased. Romberg's
      sign was positive. She had ataxic gait, orthostatic hypotension, Valsarlva
      abnormalities and hypohidrosis. Laboratory findings revealed elevated erythrocyte
      sedimentation rate, high IgG and rheumatoid factor levels, leukopenia, positive
      anti SS-A/Ro antibody and positive minor salivary gland biopsy. Axillary skin
      biopsy, CT scan cerebrospinal fluid were normal. Sensory nerve conduction
      velocity and amplitude were decreased, but motor nerve conduction velocity was
      normal. Sural nerve biopsy was characterized by loss of large and small
      myelinated fibers. All findings found in our patient were consistent with those
      of thirteen patients reported by Griffin et al in 1990 who postulated that T-cell
      inflammation of the dorsal root ganglion was an extraglandular site of autoimmune
      attack in Sjogren's syndrome.

PMID- 7732484
TI  - [Periprosthetic osteolysis ("particle disease")].

PMID- 7732485
TI  - [Stromelysin-1 (MMP-3) level in the sera from patients with rheumatoid arthritis
      and other connective tissue diseases--clinical significances in early onset
      rheumatoid arthritis].
AB  - Stromelysin-1 (MMP-3) is a metalloproteinase that degrades articular cartilage
      matrix in patients with rheumatoid arthritis (RA). We measured MMP-3 in the sera
      from patients with RA and other connective tissue diseases using specific
      sandwich EIA and studied its clinical significance in early onset RA. MMP-3 level
      in healthy control (n = 170) was significantly higher in male than in female. The
      level of MMP-3 in RA was significantly and dramatically higher than in healthy
      control, osteoarthritis, systemic lupus erythematosus, progressive systemic
      sclerosis, primary sjogren's syndrome, mixed connective tissue disease, gouty
      arthritis and traumatic arthritis. Serum MMP-3 significantly correlated with
      serum BUN or serum creatinine levels in SLE patients but not in RA patients. In
      early onset RA, serum MMP-3 level was significantly elevated. Furthermore, when
      the relationship between the serum MMP-3 level and X-ray findings of the joints
      in RA was studied, it was found that MMP-3 level was elevated even in stage I or
      II and that there was no statistical differences between stage I or II and stage
      III or IV, suggesting that serum MMP-3 level is elevated in the early stage of
      initial inflammatory process when only mild cartilage degradation is seen. These
      results suggest that measurements of serum MMP-3 is an important tool for
      establishing diagnosis of early onset RA, and that serum MMP-3 level may be a
      marker of cartilage destruction and of estimating therapeutic efficacy in early
      onset RA.

PMID- 7732486
TI  - [Progressive systemic sclerosis (PSS) and cancer--increasing coincidence rate of
      cancer in 67 PSS patients].
AB  - The coincidence rate of cancer and PSS has been increasing according to reports
      from Nippon Byori Boken Shuho (Annual of Pathological Autopsy Cases in Japan),
      reaching 12.3% in the most recent report. Therefore we reviewed the histories of
      67 PSS patients seen at our division over an 18-year period between 1974 and
      1992, and found a high coincidence rate (14.6%) of cancer, reflecting the
      increasing tendency reported in the Nippon Byori Boken Shuho. The most frequent
      type of cancer was gastrointestinal cancer, including gastric and colon cancer
      and duodenal carcinoid. There were no significant differences in the clinical and
      laboratory findings between PSS patients with cancer and those without. Twenty
      six of the 67 PSS patients died. Cancer was the cause of death in four, ranking
      second behind respiratory failure. The reason for the increasing coincidence rate
      of cancer and PSS is unclear at present. However, it is very important to
      discover cancer in PSS patients as early as possible, since it has a marked
      effect on prognosis.

PMID- 7732487
TI  - [Sleep apnea syndrome in rheumatoid arthritis (RA) patients complicated with
      cervical and temporomandibular lesions].
AB  - All-night polysomnographic studies were performed on ten patients (all female)
      with rheumatoid arthritis complicated with temporomandibular joint destruction
      and cervical lesions. The mean age of these subjects was 67.5 yrs, ranging from
      48-81 yr. They all had some morphologic abnormalities of cervical spines and/or
      temporomandibular joints. Sleep study revealed that all of them had sleep apnea;
      five of them were of obstructive type (obstructive group) while the remaining
      showed central type of sleep apnea (central group) predominantly. There were no
      statistically significant differences of the levels of apnea index, mean-nadir
      SO2 and the lowest SO2 between the obstructive group and the central group. No
      detectable differences of cephalographic measurements and MRI findings existed
      between the two groups either. In one patient, nasal-CPAP converted central apnea
      to normal breathing dramatically. Our observations indicate that the cause of
      central apnea in RA patients with temporomandibular lesions is collapse of upper
      airway, inducing inhibitory inputs from the mechanoreceptors in that region.

PMID- 7732488
TI  - [Optic neuropathy in systemic lupus erythematosus (SLE)--analysis of 54 cases
      including our case].
AB  - A 46-year old woman with systemic lupus erythematosus (SLE) who had been treated
      with oral administration of prednisolone (7.5 mg/5 mg on alternate days) at our
      outpatient clinic suddenly developed a loss of visual acuity, visual field
      defect, and photophobia on Dec. 15th, 1993. When she was admitted three days
      later, she was diagnosed as having optic neuropathy, and immediate treatment with
      methylprednisolone (1 g/day for three days) followed by prednisolone (50 mg/day)
      resulted in complete disappearance of the above symptoms by Feb. 9th, 1994. As
      far as we know, fifty-three cases of SLE with optic neuropathy have been reported
      previously. The result of analysis of the 54 cases including our case indicates
      that rapid diagnosis and corticosteroid treatment in an early phase of optic
      neuropathy leads to significant improvement.

PMID- 7732489
TI  - [Immunoglobulin and LST in RA patients treated with bucillamine].
AB  - In 79 RA patients treated with Bucillamine (Bu) we monitored IgG, A, M and total
      protein concentration x gamma-globulin% (Ig) before and after Bu. All of these
      four were lowered after Bu in both groups with and without adverse reaction. In
      the group with adverse reactions the serum level of IgG, A and Ig was
      significantly lower after Bu treatment than in the group without adverse
      reactions. The decreases of IgG and IgA were statistically significantly greater
      in the group with adverse reactions than those in the group without adverse
      reaction. The serum level of IgM after Bu in the effective group was
      significantly lower than that in the non-effective group. We also examined
      lymphocyte stimulation test (LST) in 44 RA patients treated with Bu. In the
      effective group Bu inhibited lymphocyte proliferative response to PPD more
      significantly than in the non-effective group. Bu also inhibited lymphocyte
      proliferative response after stimulation with PPD in the non-effective group
      doseresponsively. We concluded that the considerable decreases of IgG and IgA
      might correlate with the adverse reactions of Bu. The decrease of IgM and
      inhibition of LST with Bu might correlate with the efficacy of Bu.

PMID- 7732490
TI  - [Pulmonary involvement in patients with myeloperoxidase specific-antineutrophil
      cytoplasmic antibody].
AB  - In order to examine the clinical features of pulmonary involvement in patients
      with myeloperoxidase specific-antineutrophil cytoplasmic antibody (MPO-ANCA), 46
      MPO-ANCA positive patients with collagen-vascular disease and glomerulonephritis
      were investigated. Twenty eight patients (60.8%) had pulmonary involvement
      without tumor and infection, 20 (43.5%) of MPO-ANCA positive patients had
      interstitial pneumonitis, 11 (23.9%) had pulmonary hemorrhage, 3 had asthma
      (6.5%) and 7 had both interstitial pneumonitis and pulmonary hemorrhage. Patients
      with pulmonary involvement were older (mean age 61.1) and they had higher
      inflammatory acute phase reactants and higher mortality (42.9%) than patients
      without pulmonary involvement. Pulmonary hemorrhage revealed on both lung fields
      in 10 patients, 7 patients required artificial respirator and 6 died. Titer of
      MPO-ANCA increased paralleled with progression of pulmonary hemorrhage.
      Interstitial fibrosis revealed predominantly lower and lateral side of the lung.
      It is suggested that MPO-ANCA may be closely related to the pathogenesis of
      pulmonary hemorrhage and interstitial pneumonia. Careful management is needed in
      patients with pulmonary involvement, especially pulmonary hemorrhage in patients
      with MPO-ANCA.

PMID- 7732491
TI  - [Analysis of cases showing adverse reactions toward many kinds of DMARDs].
AB  - There are only six DMARDs (disease modifying anti-rheumatic drugs) available in
      the clinical practice, such as gold sodium thiomalate, D-penicillamine,
      bucillamine, auranofin, salazosulphapyridine, and lobenzarit disodium. It is
      important to select an appropriate DMARD for the patient. However, 57 of the 171
      patients showed an adverse reaction toward one DMARD and 26 (46%) of these 57
      patients showed undesirable reactions to other DMARDs. In this paper we
      emphasized (1) that this rate 46% of adverse reaction against multiple DMARDs was
      elevated and (2) that the rate of frequency of adverse reactions against two
      drugs was elevated. The ranking orders of the frequency of the adverse reactions
      of the switching of one DMARD to another are as follows; 1. gold sodium
      thiomalate to D-penicillamine, 2. gold sodium thiomalate to bucillamine, 3. D
      penicillamine to bucillamine. Therefore, a special attention for switching DMARDs
      should be paid to the patient who has already shown an adverse reaction to one
      DMARD, and we should lower the dose of DMARDs administered to the patient. In
      addition, steroid was found not to decrease the rates of the adverse reaction
      against DMARDs.

PMID- 7732492
TI  - [Histomorphometric study of osteoporosis in rheumatoid arthritis].
AB  - A histomorphometric study of osteoporosis in rheumatoid arthritis was performed
      on thirty-eight specimens from the proximal tibial metaphysis, which were
      obtained during total knee arthroplasty. Fourteen specimens from the proximal
      tibial metaphysis of osteoarthritis patients were also histomorphometrically
      studied, and the osteoporosis in rheumatoid arthritis was compared with it in
      osteoarthritis. In nine rheumatoid arthritis patients, specimens from the iliac
      bone were obtained, and the difference between the generalized osteoporosis and
      the juxta-articular osteoporosis was evaluated. The proximal tibial metaphysis in
      rheumatoid arthritis was usually represented by a fairly low bone area and by
      thin mean trabecular thickness. No correlations were seen between
      histomorphometric parameters and the age at operation, the age of onset and the
      duration of disease. However, in patients of long duration (over 20 years), the
      bone area was very low and mean trabecular thickness was thin. In one parameter
      (scalloped surface) which shows bone resorption, there was a high correlation
      between generalized osteoporosis and juxta-articular osteoporosis in rheumatoid
      arthritis. There was no significant difference between rheumatoid arthritis and
      osteoarthritis in bone area and mean trabecular thickness. However, the scalloped
      surface of rheumatoid arthritis was significantly higher than it of
      osteoarthritis.

PMID- 7732493
TI  - [Effects of fluconazole on onychomycosis in the patients with collagen diseases].
AB  - Thirty-four patients with collagen diseases suffering from onychomycosis were
      treated with fluconazole and showed remarkable improvement. Thirty-one patients
      showed improvement while only four patients showed adverse reactions. More than
      half of the cases with onychomycosis in their fingers showed improvement within
      four weeks and complete recovery within 20 weeks after the administration of
      fluconazole. Patients with collagen diseases are liable to have onychomycosis as
      an opportunistic infection which is recalcitrant and resistant disease from the
      previous therapy. In this trial it became obvious that fluconazole was not only
      effective on onychomycosis but also a safe drug for the patients with collagen
      diseases.

PMID- 7732494
TI  - [Renal function after TKR in patients with rheumatoid arthritis who have chronic
      renal insufficiency].
AB  - Twenty three patients with RA who have chronic renal insufficiency were post
      operatively studied for changes in the renal function with TKR (total knee
      replacement). We evaluated the renal function by BUN, Creatine, PSP and Creatine
      clearance. The renal function has not grown worse in all cases. TKR is a safe
      operation for renal function with careful technique and management.

PMID- 7732495
TI  - [A case of Behcet's disease with severe esophageal stenosis treated with
      esophageal bujie].
AB  - A 50-year-old woman who had been suffering from Behcet's disease came to our
      clinic. The patient developed recurrent oral aphthae, genital ulcers, and
      folliculitis when she was 25-year-old. In 1971 the diagnosis is of Behcet's
      disease was made and oral prednisolone was started. In 1976 oral and labial
      aphthae became worse, and after healing of these aphthae, adhesion of oral angle
      developed. At that time plastic surgery for adhesion was made. In 1990 the
      patient felt difficulty in opening the mouth again and operation for mouth was
      performed. In 1991 the patient was admitted to our hospital for the third time
      because of recurrent oral aphthae, vomitting, and dysphagia. Upper
      gastrointestinal series and endoscopic examination revealed that there was severe
      stenosis in the middle portion of esophagus. Above that lesion, dilatation of
      esophagus with retention of barium was observed. Forty mg/day of prednisolone
      with liquid meal was started, and operation for stenosis of the esophagus using
      bujie was performed twice. After that operation, the patient was able to take
      solid meals. Esophageal ulceration with Behcet's disease treated with
      prednisolone was reported and discussed with the review of the literture.

PMID- 7732496
TI  - [A case of mixed connective tissue disease associated with gastric cancer and
      cancer of the uterine cervix].
AB  - We report here a very rare case of MCTD complicating double cancer. A 43-year-old
      woman with suspected MCTD was admitted because of high fever and lymphadenopathy.
      The laboratory findings indicated high titers of speckled ANA, anti-RNP, DNA and
      Scl-70, but anti-Sm. SS-A and SS-B was not detected. Chest CT and Spirogram
      revealed lung fibrosis, restrictive ventilatory impairment, and decreased
      diffusion capacity. Biopsy specimen by gastric fiberscope s screening indicated
      II c advanced type of poorly differentiated adenocarcinoma. After subtotal
      gastrectomy, she had high fever, pleuritis, leukopenia, butterfly erythema and
      hypoxemia, which were improved by 30 mg/day of oral prednisolone. One year after
      from the last operation, she had contact bleeding, and squamous cell carcinoma of
      the uterine cervix was diagnosed. She had Raynaud's phenomenon 6 months after
      from hysterectomy.

PMID- 7732497
TI  - [Three cases with systemic rheumatic diseases who developed pulmonary lesions
      suggestive of bronchiolitis obliterans organizing pneumonia].
AB  - Three cases with systemic rheumatic diseases who developed lung diseases
      compatible with BOOP were reported. Underlying diseases of these patients were:
      RA (1 case), SLE (2 cases). Respiratory symptoms were observed in one case such
      as dry cough at the time of diagnosis of BOOP. Chest radiography showed multiple
      infiltrates in 2 cases, bilateral reticular shadow in one case. In one case
      characteristic finding described as wandering shadow was observed. TBLB was done
      in 3 cases. Pathohistological findings were compatible with BOOP. Repeated
      Bacteriological examinations failed to demonstrate specific organisms implicated
      for lung lesions. Cytological studies of sputum and TBLB specimens were all
      negative for malignancy. Antibiotic agents including anti-tuberculosis drugs were
      not effective for pulmonary diseases. Moderate doses of prednisolone were
      effective in 3 cases. Although the open lung biopsy has been recommended for
      establishment of diagnosis of BOOP, in patient with systemic rheumatic diseases
      this invasive procedure is not always easily performed. Further characterizations
      of clinical and laboratory features are indicated for noninvasive diagnosis of
      BOOP.

PMID- 7732498
TI  - [A case of acute lupus pneumonitis].
AB  - Forty-five-year-old woman with systemic lupus erythematosus who had treated with
      sulindac had exacerbation of her rash and arthralgia. On her admission for
      treatment, chest X-ray showed bilateral pathy infiltrates in lower lung fields.
      We performed a transbronchial lung biopsy. Immunohistopathologic studies showed
      granular deposits of IgM and C 3 in the subendothelial area of pulmonary
      arteriolae. She was treated with prednisolone (1.0 mg/kg/day) and
      deoxyspergualin. Chest X-ray showed improvement and her serum IgG, anti-DNA
      antibodies and complement diminished quickly. We suggest that these
      immunopathologic observations may be important in the pathogenesis of the lung
      injury in systemic lupus erythematosus.

PMID- 7732499
TI  - [Successful combination therapy of cyclosporine and steroids in two cases with
      interstitial pneumonitis associated with polymyositis].
AB  - Cyclosporine is an immunosuppressive agent which is well-established in the
      transplantation of organs including kidney, liver and bone marrow. It acts by
      inhibiting the production of interleukin 2, thereby blocking both the development
      of cytotoxic lymphocytes, and the proliferation of helper T cells. T cell
      mediated muscle damage is thought to be important in the pathogenesis of
      polymyositis. And activated cytotoxic T cells are thought to play an important
      role of polymyositis/dermatomyositis with active pneumonitis. It is thereby
      likely that cyclosporine would be effective in the management of polymyositis
      with interstitial pneumonitis. We have used cyclosporine in two cases of
      corticosteroids resistant polymyositis associated with pneumonitis. The first
      case was admitted because of the relapse of polymyositis. She was partially
      responded by the high dose of steroid, but showed decreased %DLCO and increased
      AaDO2 during the therapy. And oral cyclosporine was given with steroid. Within
      two weeks, serum creatinine kinase level was reduced to normal range, and the
      improvement of pneumonitis was observed. The second case was admitted because of
      the flare of pneumonitis. She was treated with high dose of steroid with
      insufficient response. And cyclosporine was prescribed. Within two weeks of
      treatment, her symptom was relieved, and blood gas analysis showed an improvement
      of pulmonary function. And steroid could be tapered. In both cases, the initial
      dose of cyclosporine was 200 mg/day, and the optimal trough level was thought to
      be ranged 100 to 150 ng/ml. In the second case, renal dysfunction was observed
      but it was recovered by the reduction of the dose of cyclosporine. No other side
      effect was appeared.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732500
TI  - 'Tell me how to survive in conventional medicine'.

PMID- 7732501
TI  - Managed care puts physicians in impossible situation.

PMID- 7732502
TI  - Deader than Elvis. Systemwide health reform has little chance of rising from
      ashes of last year's debate.

PMID- 7732503
TI  - Anti-kickback safe harbors revisited. Proposals outline exceptions to referral
      restrictions.

PMID- 7732504
TI  - Beam me up, doctor. Telemedicine takes health care to the airwaves.

PMID- 7732505
TI  - Insulin update. Reduction in formulations simplifies treatment direction.

PMID- 7732506
TI  - Managing to manage. Texas physicians and the constraints of managed care.

PMID- 7732507
TI  - Joe Cunningham, MD. Just call him Dr. Joe.

PMID- 7732508
TI  - Managed care: the Corpus Christi story.

PMID- 7732509
TI  - PA control creates emergency department mayhem.

PMID- 7732510
TI  - [Veterinary dentistry (9). Classification, nomenclature and identification of
      animal dentition].
AB  - This article in the series about the veterinary dentistry describes how the
      various dentitions of mammals can be distinguished by their form and function.
      The number of times and manner in which teeth are shed together with the course
      of tooth eruption also determine the classification. Attention is paid to the
      nomenclature and differentiation of dental elements, how the dental formula are
      composed, and how these formulas differ for various species. The importance of a
      standardized system for classifying the position of the dental elements is
      stressed. The three-digit notation system of Triadan is recommended.

PMID- 7732511
TI  - [Tielen 10 years as Professor Animal Housing and Welfare. 'Looking at the
      animal's environment with enthusiasm'].

PMID- 7732512
TI  - [Publication decision Veterinary Domestic Tribunal concerning Article 16, 3rd
      paragraph, of the Law on Veterinary Practice 1990. The Veterinary Domestic
      Tribunal].

PMID- 7732513
TI  - Decreased counterregulatory hormone responses to insulin-induced hypoglycemia in
      patients with pancreatic diabetes having autonomic neuropathy.
AB  - Thirteen patients with pancreatic diabetes caused by calcifying pancreatitis were
      divided into 2 groups; 5 with diabetic autonomic neuropathy [AN(+) group] and 8
      without [AN(-) group]. They were subjected to an insulin-induced hypoglycemic
      stress test to evaluate their blood pancreatic glucagon, adrenalin, and cortisol
      responses. When a blood glucose level below 45 mg/100 ml was defined to be
      hypoglycemia, all the patients in the AN(-) group exhibited peripheral adrenalin
      responses, with a significant increase (mean, 19.0 times the basal level) in the
      blood adrenalin level. Among the AN(+) group, on the other hand, central nervous
      symptoms became evident rather than the peripheral adrenalin response (the blood
      adrenalin level hardly exceeded the basal level). With the exception of a single
      patient, none exhibited responses in the blood pancreatic glucagon levels. Only
      one patient showed a minimal cortisol response but the remaining 12 reacted
      normally in the cortisol release. The findings are summarized as follows: in
      pancreatic diabetes, insulin-induced hypoglycemia causes little change in
      pancreatic glucagon secretion; when the condition is complicated with autonomic
      neuropathy, central nervous symptoms develop while the blood adrenalin level
      hardly increases. These findings indicated that patients with pancreatic diabetes
      complicated with diabetic autonomic neuropathy have a risk of lapsing into an
      acute hypoglycemic coma and difficulty in recovering from the hypoglycemic state.

PMID- 7732514
TI  - The importance of prevention of sinusoidal endothelial cell injury during cold
      preservation of liver graft.
AB  - We investigated adenosine triphosphate (ATP) synthesis, lipid peroxidation, and
      activities of radical scavenging enzymes in mitochondria, as well as the
      ultrastructural morphological changes during cold preservation of swine liver
      grafts (n = 6) with either Euro Collins (EC) or University of Wisconsin (UW)
      solutions. The liver, harvested by a standard procedure, was preserved in one of
      the solutions at 4 degrees C. The values of the total adenine nucleotide and
      mitochondrial respiratory control ratio (RCR), an index of ATP synthesis,
      decreased gradually for up to 24 hr during preservation with either of the two
      solutions and there was no statistical difference between them. Chemiluminescence
      of mitochondria, an index of lipid peroxidation, in the graft preserved with EC
      solution or UW solution decreased, and after 24 hr there was no significant
      difference between the two solutions. Activities of radical scavenging enzymes
      were well maintained in any of the two solutions. Transmission electron
      microscopy (TEM) findings showed that the sinusoidal endothelial cells were
      preserved much better with UW solution than with EC solution even after 12 hr
      preservation. We concluded that UW solution, more effective for the protection
      against injuries of the sinusoidal endothelial cells during cold preservation,
      leads to better results in clinical transplantation, but this solution has no
      protective effects on energy production, nor radical scavenging enzyme activities
      of mitochondria. In the maintenance of liver graft viability, protection of the
      sinusoidal microcirculatory disturbance is more important than that of the
      mitochondrial function.

PMID- 7732515
TI  - Calcaneus and vertebrae bone mineral density values and fracture threshold.
AB  - The calcaneus bone mineral density values (BMDs) of healthy Japanese women peaked
      at 20 to 25 years of age with 435 +/- 66 mg/cm2 (mean +/- S.D.), decreased 0.51%
      on the average every year thereafter until 45 years of age, 1.72% between 45 and
      55 years (menopause) and 0.55% thereafter. The vertebrae bone mineral density
      value peaked at 30 to 35 years of age with 1.06 +/- 0.13 g/cm2 (mean +/- S.D.),
      decreased 0.67% on the average every year thereafter until 45 years of age, 1.23%
      between 45 and 55 years (menopause) and 0.70% thereafter. Mean -2.0 S.D. of the
      peak bone mass was considered appropriate as the fracture threshold for both the
      calcaneus and vertebra, judging from the BMDs of osteoporosis patients.

PMID- 7732516
TI  - Study on the elbow movement produced by functional electrical stimulation (FES).
AB  - Functional electrical stimulation (FES)-induced movements of the upper extremity
      using the electromyography (EMG)-based stimulation data, which were created on
      the basis of EMG analysis of elbow flexion and extension in a normal human
      subject, were examined. As a result of the FES to the elbow flexors and extensors
      in another normal subject, smooth and reproducible elbow flexion and extension
      were controlled. This result seems to indicate not only an advantage of EMG-based
      stimulation data in the FES but also a great potential of FES as a new technique
      for the functional anatomy of the human extremities.

PMID- 7732517
TI  - Effect of 20-methylcholanthrene on the development of atherosclerosis in LAP
      quails.
AB  - We studied the effect of 20-methylcholanthrene, a carcinogen, on atherosclerosis
      in the ascending aorta and brachiocephalic arteries of hyperlipidemic and
      atherosclerosis-prone (LAP) quail. A total of 66 quails were divided into 6
      groups and fed the following diets: Group I, basal; Group II, basal+low dose of
      carcinogen; Group III, basal + high dose of carcinogen; Group IV, basal + 0.2%
      cholesterol; Group V, basal + 0.2% cholesterol + low dose of carcinogen; and
      Group VI, basal + 0.2% of cholesterol + high dose of carcinogen. The carcinogen
      was dissolved in corn oil at 2 mg/ml and 4 mg/ml as low and high doses
      respectively, and was given orally twice weekly. Marked elevation of the serum
      cholesterol level and significant lipid-rich aortic lesions were observed in all
      the cholesterol-fed groups after 12 weeks. Although the serum cholesterol level
      in Group VI was lower than that in Group IV, the severity of the atherosclerotic
      lesion was greater in the former than in the latter. An immunohistochemical study
      showed a positive reaction of DBA, PHA and OKM-1 with the lipid-containing cells
      of aortic intimal lesions.

PMID- 7732518
TI  - Tumor induction in mice administered neonatally with bis(2-oxopropyl)nitrosamine.
AB  - ICR mice were given four subcutaneous injections of bis(2-oxopropyl)nitrosamine
      (BOP) 10, 20 and 40 mg/kg body weight, respectively, on day 1, 8, 15 and 22 of
      age. Animals treated with BOP developed mainly tumors of the lung, liver, nasal
      cavity, and pancreas. Lung tumors were histologically alveolar cell adenoma or
      adenocarcinoma at an incidence of 41-100%, hepatocellular adenoma or carcinoma 59
      96%, adenoma or adenocarcinoma of the nasal cavity 11-26%, and pancreatic acinar
      cell adenoma or anaplastic carcinoma 3-7%. No sex difference in response to BOP
      carcinogen was observed.

PMID- 7732519
TI  - The electrokinetic behavior of red blood cells from a patient with Tn syndrome by
      Doppler electrophoretic light scattering analysis.
AB  - The Tn syndrome is an acquired form of persistent mixed-field polyagglutination
      displaying two distinct populations of Tn positive (Tn) and Tn negative (tn) red
      blood cells (RBCs). We investigated the electrophoretic behavior of RBCs showing
      polyagglutination from a patient with Tn syndrome by the doppler electrophoretic
      light scattering (D.E.L.S.) analysis. The mean of zeta potential of normal RBCs
      from ten individuals was -13.07 +/- 0.61 mV (mean +/- S.D.). The content of
      membrane-associated sialic acid equated with the zeta potential of RBCs. Among
      the proteases ficin was most effective on the zeta potential of RBCs. The zeta
      potential of the patient Tn RBCs and tn RBCs were -4.73 mV and -13.32 mV,
      respectively. Tn RBCs reduced 64.5% of zeta potential compared with tn RBCs and
      formed 48.8%. These results may provide some useful information for
      classification of Tn syndrome.

PMID- 7732520
TI  - Bronchoalveolar lavage as a possible cause of acute exacerbation in idiopathic
      pulmonary fibrosis patients.
AB  - In the past 13 years (1980 to 1992), bronchoalveolar lavage (BAL) was performed
      on 124 idiopathic pulmonary fibrosis (IPF) patients (29 F and 95 M, 60 +/- 1
      years, mean +/- S.E.) at Tohoku University Clinic and Hospital. Among them, three
      patients showed acute exacerbation immediately after BAL and died of progressive
      respiratory failure after 2.5 weeks, 2 months and 3.5 months, respectively,
      despite intensive care. They were all older patients (79, 74 and 66 years old)
      and we failed to find any evidence of viral, bacterial or fungus infections
      either before or after BAL in blood, sputum or BAL fluid samples. Further, all
      autopsied lungs showed interstitial pneumonia and fibrosis and no evidence of
      infectious diseases. In contrast, no progressive deteriorations after BAL were
      observed in 282 patients (122 F and 160 M, 48 +/- 1 years old) with other
      pulmonary diseases (sarcoidosis, bronchial asthma, collagen diseases and other
      interstitial lung diseases), who received BAL during the same period. This
      suggests that BAL itself sometimes induces a progressive degeneration in IPF
      patients, especially in older patients.

PMID- 7732521
TI  - [The participation of prostaglandin F2 in the peroxidation damages and
      antiperoxidation protection of the parotid gland in acute nonepidemic parotitis].
AB  - Effects of prostaglandin F2 on the major components of the antioxidative system
      (levels of malonic dialdehyde and lipid peroxides, activities and content of
      glutathione enzymes and nonenzymes (glutathione peroxidase, glutathione
      reductase, and NADPH (NADH), oxidized and reduced glutathione) were studied in
      experiments with 60 dogs in which acute nonepidemic parotitis was modeled. A
      varying capacity of the cells of the parotid gland to resist the detrimental
      effects of the disease and specific features of prostaglandin F2 effect on this
      capacity were revealed: injection of prostaglandin F2 stimulated both lipid
      peroxidation and the activity of the antioxidative system and led to cellular
      injury in the presence of a relatively high level of cellular metabolism,
      preserving cellular viability on condition of inhibited rate of metabolic
      reactions, this being the principal factor for the parotid gland, among other
      factors determining the cytoprotective effect.

PMID- 7732522
TI  - [An experimental and clinical validation of the use of the ultraphonophoresis of
      a resorcin-formalin mixture in chronic periodontitis].
AB  - Analysis of the parameters of the resorcin-formalin mixture of 10-40%
      concentration in an ultrasonic field (28.5 kHz), study of the phoretic activity
      of these mixtures on the section specimens of removed human teeth helped develop
      the method of ultraphonophoresis of the resorcin-formalin mixture on the teeth
      with poorly patent and nonpatent radical roots in patients with chronic
      destructive periodontium. Clinical follow-up of 42 patients showed the efficacy
      of this method.

PMID- 7732523
TI  - [Human salivary lactoferrin--a new health status index].

PMID- 7732524
TI  - [The x-ray picture of cysts and cyst-like neoplasms of the mandible].
AB  - A total of 444 patients with histologically verified cysts (radicular, residual,
      traumatic, keratocysts, follicular) and some cystic formations (ameloblastomas,
      osteoclastomas, myxomas) were examined by clinical and x-ray methods. X-ray signs
      of some cystic diseases of the mandible are analyzed, x-ray symptoms which help
      differentiate between individual nosologic entities are singled out.

PMID- 7732525
TI  - [Intravenous general anesthesia with low doses of ketamine in performing complete
      oral hygiene in the outpatient practice].
AB  - A variant of total anesthesia with modified doses of ketamine was developed and
      tried in 1305 patients in an outpatient setting. Low doses of ketamine
      hydrochloride (initial dose 25-70 mg, repeated one 20-40 mg) do not lead to
      hemodynamic shifts, disorders of spontaneous respiration, and long postanesthetic
      depression. At the same time the level of anesthesia and analgesia attained is
      sufficient for complete sanitization of the oral cavity. The suggested method
      extends the indications to total anesthesia in stomatological interventions on an
      outpatient basis, is simple for anesthesiologist, and safe for the patients.

PMID- 7732526
TI  - [Current approaches to the diagnosis and treatment of temporomandibular joint
      dysfunctions].

PMID- 7732527
TI  - [The etiology of sialolithiasis].
AB  - The authors have revealed dilatation of the excretory ducts of salivary glands
      involved in sialolithiasis and of other salivary glands in a patient. A
      hypothesis on the primary etiological role of ductal ectasia in the development
      of sialolithiasis in case some other additional factors are present is put
      forward. The authors recommend resorting to computer-aided tomography and
      functional digital subtraction sialography of the salivary glands for the
      diagnosis of sialolithiasis and discuss the advantages of these methods in
      comparison with other ones.

PMID- 7732528
TI  - [A primary odontogenic cyst of the jaws (keratocyst)].
AB  - Forty-six patients (21 men and 25 women) with keratocysts were treated at Dental
      Surgery Chair of the Moscow Medical Stomatological Institute. Cystectomy was
      carried out in 26 patients, two-staged treatment in 20. Histologic examination of
      the operative material confirmed the diagnosis. A two-staged method of treatment
      of this disease in an outpatient setting has been developed. Cystectomy was
      carried out in cases with cysts up to 2-3 cm in diameter, it did not destroy the
      cortical plate of the jaw; it was performed similarly as total biopsy and was the
      final treatment modality. In cases with larger cysts, when the thickness of the
      cortical layer was less than 0.5 cm and there was a risk of fracture, two-staged
      treatment was resorted to: the first step, decompression performed similarly as
      cystostomy and the second, cystectomy a year or more after the first stage, when
      the size of the cyst reduced to 1.5-2 cm in diameter. The patients were followed
      up for up to 2-5 years after the treatment. Hence, correct and timely diagnosis
      of the disease and a two-staged method of treatment of keratocysts developed at
      out Chair bring about good results with the least injury to the patients.

PMID- 7732529
TI  - [The use of ultrasonic tomography for assessing the spread of a primary tumor of
      the mucosa in the retromolar area and for choosing the surgical treatment
      method].
AB  - Ultrasonic examination was carried out in 31 patients with stage III-IV squamous
      cell carcinoma of the retromolar mucosa. Dissemination of the tumor of the
      retromolar triangle into the stomach was detected in 14, into the adjacent
      anatomical structures in 6 patients. Combined operations with inclusion into the
      block of removed tissues of the involved structures were carried out due to the
      information obtained. The data of ultrasonic tomography were confirmed by
      morphologic examinations of removed preparations.

PMID- 7732530
TI  - [Sialography with direct multiple image enlargement and the processing of the
      sialograms on an analog computer].
AB  - To extend the potentialities of sialography, we used roentgenography with direct
      multiple amplification of the image by Reis microfocal portable x-ray diagnostic
      device and analyzed this image by analog UAR-1 computer operating in a high
      frequency harmonization mode. The basic feature of such roentgenography is
      spatial stratification of the object shadow simultaneously forming its spatial
      image. High-frequency harmonization of an x-ray image essentially improved its
      contrast, this permitting detection of small formations poorly shown on
      sialogram, the contours of these formations and relationships between them. A
      total of 85 patients were examined using this method. Analysis of the resultant
      sialograms showed that using this method it is possible to assess the status of
      small structures of the gland, detect the changes in the pharyngeal process of
      the parotid gland. Sialogram direct projection is no longer needed.

PMID- 7732531
TI  - [The intensity of protein biosynthesis in the periodontium].
AB  - The intensity of protein biosynthesis in clinically healthy gingival tissues is
      the maximal at young age (20 to 30) and reduced in older subjects (aged 40 to
      50). In generalized periodontitis the intensity of protein biosynthesis is
      reliably increased, more markedly in exacerbations and less so in a chronic
      course. An acute course is characterized by an approximately similar increases in
      the activity of protein synthesis in disease of varying severity. In an acute
      course the intensity of biosynthesis was the minimal in cases with the slight and
      the maximal in patients with grave generalized periodontitis. The content of
      sulfhydryl groups in the gingiva in generalized periodontitis is increased; it
      does not depend on the disease severity in an acute course of the disease,
      whereas in a chronic course this value is the maximal in cases with slight and
      the minimal in grave generalized periodontitis.

PMID- 7732532
TI  - [The surgical treatment of maxillary micrognathia in patients after cheilo- and
      uranoplasty].
AB  - A new method for surgical treatment of upper micrognathia is offered. Osteotomy
      of only the anterior segment of nasal septum is carried out to reduce blood loss,
      make the operation less traumatic and circulatory disturbances less severe in the
      mobilized fragment of the maxilla. Osteotomy of tubercles and anterior surfaces
      of the maxilla is carried out subperiosteally. Use of this method in 12 patients
      with upper micrognathia after cheilo- and uranoplasty helped attain good esthetic
      and anatomicofunctional results.

PMID- 7732533
TI  - [The restoration of teeth with subgingival fractures].
AB  - The authors review the history of forced advancing of teeth and describe 10
      patients with 10 upper teeth (3 lateral and 6 central canines and 1 first molar)
      with root fractures near the alveolar osseous crest which were treated by
      orthodontic forced advancing of the roots. For this purpose an orthodontic device
      consisting of an arch, provisional pin with a hook, and elastic traction were
      used. The rate of tooth advancing and time of adjacent periodontium
      rehabilitation were measured. The treatment was effective in all the cases, this
      recommending it for wide dental practice.

PMID- 7732534
TI  - [The orthodontic treatment of traumatic occlusion in sagittal bite anomalies].
AB  - A total of 288 patients (100 females and 188 males) aged 25 to 60 with prognathic
      and progenic occlusion were examined and treated. Dentition deformations were
      revealed in 182 (63.1%) patients. Clinical and x-ray signs of traumatic occlusion
      were observed in 219 (76.04%) cases. Abnormal mobility of teeth was detected in
      181 (79%) subjects with prognathic occlusion, dentogingival and osseous pouches
      in 164 (71.6%) subjects. Reduced height of occlusion was found in 68 (25.3%),
      dysfunction of the temporomandibular joint in 19 (8.2%) cases. Traumatic
      occlusion was observed in 38 of the 59 patients with progenic occlusion. In
      sagittal abnormalities of occlusion, traumatic occlusion was associated with
      dysfunctions of the masticatory muscles and of local circulation in the
      periodontium, which were recorded by electromyography and rheoparodontography.
      The treatment was carried out by therapists, surgeons, and orthodontists.
      Orthodontic treatment consisted in levelling of the occlusion surface of
      dentitions, orthodontic preparation of the maxillodental system, fitting with
      splints and prostheses. Remote results in periods from 1 to 3 years were good in
      94.8% of patients.

PMID- 7732535
TI  - [The functional value of complete dentures depending on the arrangement of the
      artificial teeth].
AB  - Adhesion, functional adhesion, and observation of mechanical regularities during
      repair of dentition in patients with complete loss of teeth ensure stability of
      complete dentures and, hence, their functional value. Since functional adhesion
      is frequently impossible to provide as far as it concerns the lower denture, such
      dentures are always liable to the action of dumping force. The authors describe a
      method for making artificial teeth of complete removable dentures with due
      consideration for the individual force of occlusion of the jaws and the teeth
      inclination angle determined individually for each patient.

PMID- 7732536
TI  - [Changes in the properties of the enamel of the permanent teeth in children using
      fluoride-containing toothpastes].
AB  - Focal demineralization of the enamel of permanent teeth was studied in 104
      schoolchildren aged 9 to 12 over the course of prophylaxis (cleaning the teeth
      with fluorine-containing toothpastes). The parameters checked up were the
      intensity of coloring, size and electric conductivity of the spots, and the rate
      of remineralization of the enamel of permanent teeth. For a year a strong
      correlation between the tested characteristics of the enamel and saliva was
      observed. Some age-specific characteristics of permanent teeth enamel were
      detected. Age group of 11 to 12 years should be distinguished in prophylactic and
      control groups, because it is at this age that all the tested properties of the
      enamel are the most liable to change: electric conductivity, permeability, and
      remineralization rate. This period seems to be characterized by a specific
      reaction of all systems and organs of the body to environmental exposures.
      Remineralizing prophylaxis was found to be the most effective at the age of 9 to
      10 years. The findings permit us emphasize the contribution of fluorine contained
      in the Blendax fluorine-containing toothpaste used by the children to the major
      components of the pathologic process (white spots) and enamel remineralization at
      the stage of its maturation.

PMID- 7732537
TI  - [Primary rhinocheiloplasty in bilateral incomplete clefts of the upper lip].
AB  - Anthropometric examinations of 31 patients with bilateral incomplete clefts of
      the upper lip revealed an excessive elongation of the lateral fragments and
      reduced height of the central part of cleft lip. Two methods of primary
      rhinocheiloplasty are suggested, depending on the degree of prolabium
      underdevelopment, both of them permitting levelling of the height of the
      fragments and repair of anatomically correct shape of the upper lip and nose.
      Preparation and connection of the stumps of the oral orbicular muscle during the
      operation are conductive to recovery of the function of the upper lip, which is
      confirmed by electromyography data.

PMID- 7732538
TI  - [Biochemical and ultrastructural changes in the periodontium during the chronic
      administration of pro-oxidant xenobiotics].
AB  - Effects of chronic administration of xenobiotics pro-oxidants on the state of
      periodontal tissues, level of free-radical oxidation of lipids, and antioxidant
      provision were studied. Diphenin and delagil were found to promote biochemical
      and morphological changes similar to the manifestations observed in
      periodontitis. A conclusion is made about an important role of nonenzymatic free
      radical oxidation of lipids and biopolymers in the pathogenesis of periodontitis.
      The principal stages of contribution of autooxidation to the parodontogenesis are
      presented.

PMID- 7732539
TI  - [The effect of periodontal cytomedin on free-radical lipid oxidation and on
      antiaggregation activity in the periodontium in chronic stress].
AB  - Effects of polypeptide bioregulators isolated from periodontal tissue on free
      radical oxidation of lipids and the microcirculatory hemostasis during the
      development of chronic stress were under study. Increased reactions of lipid free
      radical oxidation and blood hydrocortisone levels, denudation of dental necks
      were observed in animals during stress, which was explained by disordered
      reaction of microcirculatory hemostasis assessed from the antiaggregation
      activity of the periodontium. Administration of a polypeptide bioregulator led to
      a reduction of free-radical oxidation of lipids, to an increase in the activities
      of antioxidative enzymes, and hence, to a reduction of the injury to the cellular
      structures of the periodontium due to decrease of disorders of the
      microcirculatory hemostasis and ischemia in it.

PMID- 7732540
TI  - [The classification of defects in the dental arches of children and orthodontic
      treatment methods].
AB  - Dentition defects occurring in children are classified into 6 classes with
      subclasses in some of them. Class I includes dentition with defects in the
      frontal part, class II includes dentitions with distal defects. Both classes
      include special subclasses for dentition with defects of deciduous teeth, of
      permanent teeth with underdeveloped roots, and of permanent teeth with mature
      roots. Non-distal dentition defects (class III) are divided into two subclasses:
      unilateral and bilateral. Class IV includes dentition with multiple defects in
      various age groups. Dentition defects combined with maxillofacial abnormalities,
      deformations, and defects are classified as class V. Primary hypo- and anodontia
      are referred to class VI. Indications to fitting with removable plate prostheses,
      permanent bridge prostheses, and prosthetic devices of various design to repair
      the defects of various localization, extent, and the degree of development of the
      maxillofacial area are defined. Special attention is paid to fixation of
      prostheses, the most intricate problem in prostheses of dentition defects in
      children. The suggested classification is practically important for the diagnosis
      and planning of orthodontic treatment of children with dentition defects.

PMID- 7732541
TI  - [Experience in preventing dental caries in the children of a city with a low
      fluorine content in its water].
AB  - Examinations of the dental status of 12-year-old children of the same schools of
      the town of Baranovichi in various years of two decades, from 1970 to 1990,
      showed an increase in the incidence and intensity of dental caries up to the year
      1986. After a program of caries prevention was introduced in 1990, these
      parameters reduced. Local and systemic prophylactic means were tested and
      introduced in a complex of prophylactic measures. The best prophylactic effect
      was attained in children aged 9 administered sodium fluoride tablets since the
      age of 2 in comparison with the children administered such tablets since the age
      of 6. Efficacy of fluorine varnish and sealing of fissures on permanent molars
      with vitacryl was assessed.

PMID- 7732542
TI  - [A method for extracting broken endodontic instruments left in immediate
      proximity to the root canal opening].
AB  - In order to remove the fragment of an instrument, filling material evicrol is
      applied onto the mouth of the root canal in which the end part of the broken
      instrument is detectable; the second half of the endodontic instrument is
      introduced in evicrol substance. After evicrol hardening the two parts of the
      instrument are reliably connected, and thus the fragment may be removed from the
      root canal.

PMID- 7732543
TI  - [A psychological analysis of conflict situations in an outpatient dental
      consultation].

PMID- 7732544
TI  - [The medical college teacher--a key figure in specialist training].

PMID- 7732545
TI  - [Reflections on the culture of scientific criticism].

PMID- 7732546
TI  - [The problems in studying the prevalence and the organization of the prevention
      of maxillodental anomalies in children].
AB  - Methodological aspects of studies of the prevalence and organization of
      prevention of maxillodental abnormalities in children are discussed, effects of a
      number of factors on the incidence of such abnormalities shown. The author
      emphasizes that prevention of abnormalities should start in early age and be
      based on an individual approach to a child. A conclusion is made on the necessity
      of development of a unified program of epidemiological study of abnormalities in
      the country.

PMID- 7732547
TI  - [D. A. Entin--the founder of Russian military stomatology].

PMID- 7732548
TI  - [Periodontal function after replantation].
AB  - The components of periodontal connective tissue were studied on days 28-30 after
      replantation of the teeth with the extra-alveolar time 5, 15, and 30 min. The
      levels of collagen, glucosaminoglycanes, sialic acids, and activity of sialidase
      increased at extra-alveolar time 30 min by 44, 33, and 20, and 85%, respectively.
      Introduction of potassium hyaluronate in dental wells reduced the sail collagen
      growth in the periodontal tissue.

PMID- 7732549
TI  - [Reparative osteogenesis in the implantation of different modifications of a
      biocompatible polymer].
AB  - Presents a histological picture of the time course of repair osteogenesis in
      replacement of bone tissue defects with implants made of 4 various copolymers of
      N-vinylpyrrolidone. Demonstrates excellent morphofunctional qualities of newly
      formed tissue substrate and its maturity in replacement of bone tissue defects
      with implants of N-vinylpyrrolidone with butylmethacrylate.

PMID- 7732550
TI  - In situ splitting of the liver in the heart-beating cadaveric organ donor for
      transplantation in two recipients.
AB  - SLT presents an interesting concept to alleviate the organ shortage for children
      with end-stage liver disease. The procedure has, however, not gained wide
      acceptance. This is not only related to the complexity of the procedure, but also
      to the poorer results and the complications reported on the right side graft. We
      report on a first case in which we applied a new concept for splitting. The liver
      was split in situ in the heart-beating cadaveric donor with the aim of reducing
      the problems with the right side graft. This procedure makes splitting of the
      liver possible without submitting the recipient of the right side to increased
      risk. Therefore, in situ splitting of the liver has the potential of making
      splitting of liver grafts the rule rather than the exception, thus increasing the
      organ pool for small children presently carrying a high risk of dying on the
      waiting list.

PMID- 7732551
TI  - Rapamycin graft pretreatment in small bowel and kidney transplantation in the
      rat.
AB  - The effect of rapamycin (RAPA) as graft pretreatment was evaluated in orthotopic
      small bowel and kidney allotransplantation (Tx) in the rat. In the small bowel Tx
      model, six groups were involved, each including three combinations for evaluation
      of host-versus-graft (HVG) [Lewis (LEW) x Brown Norway (BN) (LBN)-F1-->Lewis],
      graft-versus-host (GVH) (LEW-->F1), and combined HVG and GVH immune responses (BN
      ->LEW). RAPA graft pretreatment alone (16 micrograms/ml x 3 ml) was able to
      induce a modest but significant prolongation of survival in all three combination
      models compared with controls (P < 0.05). The same was observed for low dose CsA
      treatment (2 mg/kg/day x 14 days) of the recipient only (P < 0.05). Combination
      of graft pretreatment with RAPA and CsA recipient treatment produced a marked
      prolongation of survival especially in HVG response. Recipients treatment with
      one 48-microgram bolus of RAPA i.v. immediately after graft revascularization
      failed to achieve any prolongation of survival for the GVH or combined HVG and
      GVH responses. This seems to exclude a "carry-over" effect of RAPA from graft to
      recipient. RAPA efficacy was also clearly confirmed in the kidney graft
      pretreatment model as compared to recipient treatment with an equivalent RAPA
      dose. These results demonstrate that graft RAPA pretreatment prolongs SB survival
      after Tx in the rat for HVG, GVH, and bidirectional immune responses. Intragraft
      interaction with passenger leukocytes or APC function appears as one of the
      possible mechanisms. RAPA graft pretreatment potentiates low dose CsA recipient
      treatment suggesting a possible use in clinical organ Tx.

PMID- 7732552
TI  - Comparison of Eurocollins and University of Wisconsin solution in single flush
      preservation of the ischemic reperfused lung: an in vivo rabbit model.
AB  - The standard preservation technique in lung transplantation is cold single
      pulmonary artery flush (PAF) with Eurocollins solution (ECS). We compared ECS
      with University of Wisconsin (UW) solution, with and without added indomethacin,
      in single PAF preservation in an in vivo rabbit model of warm ischemia
      reperfusion lung injury. Six groups of four New Zealand white rabbits each
      underwent isolation and hilar stripping of the left lung. In the four
      experimental groups, the left lung was flushed with (15 ml/kg) of cold ECS or UW
      solution, with or without added indomethacin, before warm ischemia for 120
      minutes and before reperfusion for 60 minutes. The remaining two groups were the
      nonischemic and the ischemic "no flush" controls. Transcapillary flux of
      99mTechnitium-labeled albumin and electron microscopy were used to demonstrate
      lung injury. Pulmonary vascular resistance (PVR) and thromboxane B2 (TXB2)
      concentrations were measured. There was a significant rise in PVR after
      ischemia/reperfusion in the ischemic control group (54.7 +/- 13.9 to 117.8 +/-
      20.7 mm Hg/L.min-1, P < 0.05). The net rise in PVR after ischemia-reperfusion was
      significantly smaller in the two groups in which indomethacin was added (16.8 +/-
      17.5 and 4.5 +/- 10.6 mm Hg/L.min-1 for UW and ECS, respectively) compared with
      the ischemic control (63.1 +/- 24.6 mm Hg/L.min-1, P < 0.05). Post-reperfusion
      TXB2 levels tended to be lower in the nonischemic control group and in the
      indomethacin-flush groups. We conclude that the increase in PVR produced by
      unilateral ischemia-reperfusion lung injury in this model was improved by single
      PAF perfusion. There was no significant difference between UW solution and ECS in
      this regard. The addition of indomethacin to the flush solution was associated
      with lower PVRs as well as morphologic improvement by electron microscopy. These
      findings may indicate a prominent role for the provision of PG synthesis
      inhibition during preservation for lung transplantation.

PMID- 7732553
TI  - Thromboxane synthase inhibitor, UK 38485, prevents renal injury in the rabbit
      isolated perfused kidney exposed to cold ischemia.
AB  - Recent studies have indicated that, the administration of thromboxane A2 (TxA2)
      inhibitors improved renal functions in experimental renal allograft
      transplantation. Thus TxA2, a vasoconstrictor metabolite of arachidonic acid, may
      play a role in renal function and blood flow during hypothermic storage. The aim
      of the present study was to evaluate the cytoprotective effect of TxA2 synthase
      inhibitor, UK 38485, on altered renal function due to cold ischemia for 24 and 72
      h. Experiments were performed in isolated perfused kidney from adult rabbits.
      Kidneys were perfused with Euro-Collins (EC) containing UK 38485 and incubated
      with the same solution in a beaker exposed to cold ischemia for 24 and 72 h. The
      same procedure was applied to the control kidneys in EC solution alone. Vascular
      responses and urinary output to noradrenaline, angiotensin II, endothelin-1,
      acetylcholine, and sympathetic stimulation were assessed as the functional
      activity of kidney. The addition of UK 38485 to EC solution increased the
      preservation time of kidney and protects the vascular endothelial regulatory
      functions and urine excretion when compared to EC alone. The results of the
      present study can be taken as an evidence of the cytoprotective effect of the UK
      38485 and might be useful for kidney preservation.

PMID- 7732554
TI  - Acute graft loss secondary to necrotizing vasculitis. Evidence for cytokine
      mediated Shwartzman reaction in clinical kidney transplantation.
AB  - A small number of kidney transplant recipients abruptly lose function secondary
      to acute renal artery or vein thrombosis or more rarely a form of necrotizing
      vasculitis. We report a group of four kidney transplant recipients who lost renal
      function and share the following features: (1) diabetes (type I, insulin
      dependent diabetes mellitus, type II or steroid-induced); (2) abrupt change/loss
      of renal function; (3) a concomitant clinical event (fever, viral symptoms,
      menometrorrhagia, viremia, bacteremia); (4) severe necrotizing vasculitis with
      hemorrhagic necrosis on histopathology; (5) patent renal artery and vein at time
      of transplant nephrectomy (i.e., no vascular thrombosis); and (6) high levels of
      peripheral serum gamma-IFN 1-5 days before transplant nephrectomy (467 +/- 175
      pg/ml) compared with that of patients experiencing severe rejection (8.4 +/- 3.7
      pg/ml) (P < 0.002). These data support the concept of a cytokine (IFN-gamma)
      mediated accelerated inflammatory response resulting in graft loss from
      necrotizing vasculitis--the clinical equivalent of an organ-specific Shwartzman
      reaction.

PMID- 7732555
TI  - Early improvement in cardiac function occurs for pancreas-kidney but not diabetic
      kidney-alone transplant recipients.
AB  - Noninvasive M mode echocardiography with Doppler recording was prospectively
      performed on type I diabetic recipients of pancreas-kidney (n = 20), pancreas
      after-kidney (n = 2), and kidney-alone (n = 11) allografts to determine whether
      the return of euglycemia by pancreas transplantation in the uremic diabetic
      person was associated with improved cardiac function. Each patient was studied
      preoperatively and at 6 and 12 months posttransplant. Echocardiographic
      parameters which were compared included measures of systolic function (shortening
      fraction), diastolic function (early/active peak velocity ratio, early/active
      integral ratio), and left ventricular geometric parameters (interventricular
      septal thickness, posterior wall thickness, left ventricular mass). The only
      statistically significant improvement observed for kidney-alone recipients was an
      increased shortening fraction from baseline (24.91%) to 6 months (32.13%, P < or
      = 0.0188). In contrast, the pancreas group demonstrated sustained improvement in
      all outcomes with measures at 12 months consistently showing a significant
      improvement from baseline which was also significantly better than that reported
      for the kidney-alone group. This study showed stabilization of cardiac function
      by echocardiography for diabetic kidney-alone recipients, whereas significant
      improvement in function occurred for pancreas-kidney recipients. The improvement
      in cardiac function for pancreas recipients was seen at 6 months with continued
      improvement evident at 12 months.

PMID- 7732556
TI  - High frequency of IL-10-secreting CD4+ graft-infiltrating T lymphocytes in
      promptly rejected kidney allografts.
AB  - IFN-gamma and IL-10 secretion by sorted T cell subsets of irreversibly rejected
      kidney graft-infiltrating cells (GIC) and normal PBMC was studied by ELISPOT. The
      low spontaneous frequency of IFN-gamma-producing cells (IFN-gamma-PC) was
      strongly increased by anti-CD3 activation within unsorted, CD3+CD4+, and CD3+CD4-
      subsets of GIC and PBMC. In contrast with PBMC, IL-10-PC from GIC were at higher
      frequency within CD4+ cells than among CD4- ones (P < 0.03). Four kidneys removed
      after 3.7 +/- 0.8 months showed acute vascular rejection, high frequency of
      activated CD4+ IL-10-PC (118 +/- 68 per 10(4) cells), and high percentage of anti
      class II antibody reactivity (87.6 +/- 6.3%). In contrast, four patients with
      kidneys removed later (53.7 +/- 1.6 months, P = 0.02) displayed chronic rejection
      with superimposed acute cellular rejection, low frequency of CD4+ IL-10-PC (7.0
      +/- 3.0 per 10(4) cells, P = 0.02), and low percentage of anti-class II antibody
      reactivity (12.9 +/- 6.1%, P = 0.02). Thus, accelerated vascular rejection
      appears to be associated with preferential production of IL-10 by activated CD4+
      GIC, which may act by shifting the effector arms of alloreaction toward humoral
      responses.

PMID- 7732557
TI  - CsA levels in the early posttransplant period--predictive of chronic rejection in
      liver transplantation?
AB  - The increasing success of clinical liver transplantation has brought rejection to
      the forefront as a cause of morbidity and graft loss. The relationship of
      immunosuppressive drug doses and levels to acute and chronic rejection remains a
      matter of debate. The effect of blood CsA levels and drug doses on the incidence
      of acute and chronic rejection and the impact of acute rejection episodes on the
      occurrence of chronic rejection were studied in 146 grafts in 132 patients. These
      patients were transplanted in the 4-year period from June 1989 using CsA-based
      immunosuppression (CsA, azathioprine, prednisolone). Liver grafts in patients
      maintained on median CsA levels (whole blood, trough level) of > or = 175
      micrograms/L in the first 28 days posttransplant had a significantly lower
      incidence of chronic rejection (2 out of 49 vs. 22 out of 97; P = 0.002). There
      was no significant difference in incidence of graft loss due to fatal sepsis (6%
      vs. 5%) or nephrotoxicity between the high and low CsA level groups. The overall
      graft loss rate was lower in the higher CsA level group (22% vs. 37%). The total
      doses of the individual drugs did not correlate with the incidence of acute or
      chronic rejection. Although the occurrence of acute rejection itself did not
      determine later chronic rejection, late occurrence (P < 0.00001) and multiple
      episodes (two or more; P = 0.0002) of acute rejection were significant risk
      factors for the occurrence of chronic rejection. We conclude that to minimize
      graft loss to rejection, CsA levels should be maintained at greater than 175
      micrograms/L in the early posttransplant period, and late and recurrent episodes
      of acute rejection should be prevented.

PMID- 7732558
TI  - The use of ABO-incompatible grafts in liver transplantation: a life-saving
      procedure in highly selected patients.
AB  - The aim of this study was to assess the long term results of 43 ABO-incompatible
      liver transplantations performed in 40 patients. The 5-year patient and graft
      survival rates were 50 and 20%, respectively. In the group of patients
      transplanted in emergency for fulminant or subfulminant liver failure, ABO
      incompatibility had no significant impact on patient survival (P = 0.09). Graft
      survival, however, was significantly impaired (P = 0.0002) through a greater
      incidence of hyperacute rejection (20%), vascular thrombosis, and biliary injury
      (56%). Increasing the magnitude of immunosuppression and postoperatively reducing
      the titer of anti A/B antibodies by plasmapheresis had little influence on the
      incidence of these complications and were associated with a greater incidence of
      septic complications. These results indicate that the use of ABO-incompatible
      liver grafts is a life-saving procedure in patients with life-threatening acute
      liver failure, but at a high price. Justification for accepting or not accepting
      an ABO-incompatible graft in these emergency situations depends on the personal
      choice in giving priority to saving the patient in an acute life-threatening
      condition or to giving the graft the best chance of success. To avoid this
      difficult choice, efforts should aim at expanding the pool of grafts available in
      emergency, at developing artificial support devices that could allow to safely
      delay transplantation, or at more efficiently controlling the humoral response.

PMID- 7732559
TI  - Comparison of polymerase chain reaction from plasma and buffy coat with antigen
      detection and occurrence of immunoglobulin M for the demonstration of
      cytomegalovirus infection after liver transplantation.
AB  - We compared the value of PCR on plasma with PCR on buffy coat leukocytes, Ag
      assay, and the determination of IgM antibodies by ELISA for the diagnosis and
      follow-up of cytomegalovirus infection. Thirty patients were followed after liver
      transplantation (LTX). We compared the tests to assess their clinical usefulness.
      Fourteen of 30 (46%) patients were both positive in plasma and buffy coat PCR and
      Ag test. Sixteen patients were negative in both procedures. There was a 97.2%
      concordance between PCRs done from plasma or buffy coat. The concordance of
      results of PCR and Ag test in single samples was 94.3%. Discordant results were
      found in 5.6% of samples. Discordance was observed in the early and the late
      phase of CMV infection and was due to positive PCRs preceding positive Ag tests
      for 1-3 weeks in one-half of the patients. IgM antibodies were first observed
      after a median period of 8 weeks (range, 6-11 weeks) after LTX. Positive PCRs and
      Ag tests preceded clinical manifestation of CMV disease by a 1 week median
      (range, 0-3 weeks), whereas positive IgM ELISAs occurred after a median period of
      2.5 weeks (range, 0-4 weeks) after the onset of CMV disease. The sensitivity and
      specificity of both PCR and Ag test were identical, 100% and 76%, respectively.
      However, for the IgM ELISA, the sensitivity was only 66%, and the specificity was
      84%. In conclusion, plasma or buffy coat PCR and Ag test are equally reliable
      procedures for early detection and monitoring of CMV infection. PCR can become
      positive earlier than the Ag test, but it is technically more demanding to
      perform. The demonstration of IgM antibodies is of little practical help because
      an antibody response occurs too late in relation to infection.

PMID- 7732560
TI  - Liver disease after bone marrow transplantation--the Taiwan experience.
AB  - To investigate the causes of impaired liver function (LF)* after BMT, 88 patients
      were included for analysis of hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infections, transplant methods, preconditioning regimens, and graft-versus-host
      disease (GVHD). Fifty of them (56.8%) developed abnormal LF after BMT and among
      them, 29 (32.9%) developed chronic hepatitis (CH). By univariate analysis, HCV
      infection, pretransplant abnormal LF, allogeneic BMT, and preconditioning regimen
      with total body irradiation were all significantly related to higher incidence of
      post-BMT impaired LF. However, only HCV infection, pretransplant abnormal LF, and
      acute GVHD were associated with higher incidence of CH. By multivariate logistic
      regression analysis, HCV infection and pretransplant abnormal LF were the two
      most significant interpreters for abnormal LF, especially for CH (odds ratios:
      7.86 and 4.735, respectively) after BMT. Although the incidence of abnormal LF
      was found high in this study, there was no significant disadvantage in terms of
      survival for patients who developed abnormal acute and chronic liver function
      after BMT. However, a long-term follow-up is needed to evaluate survival
      pathology of CH, such as liver cirrhosis and hepatoma.

PMID- 7732561
TI  - Efficacy of a 6-week prophylactic ganciclovir regimen and the role of serial
      cytomegalovirus antibody testing in lung transplant recipients.
AB  - CMV is a frequently occurring pathogen in recipients of solid organ transplants,
      and those receiving lung transplants seem to be affected more frequently and more
      severely. Because the duration of prophylactic ganciclovir may influence the
      incidence of CMV disease in solid organ transplant recipients, we evaluated the
      efficacy of a 6-week prophylactic regimen in lung transplant recipients. We also
      evaluated the ability of a fourfold rise in CMV antibody titer to predict the
      development of CMV disease. Twenty-one consecutive lung transplant recipients
      were enrolled: 15 were CMV antibody-positive at the time of transplantation, and
      six were CMV antibody-negative and received a lung transplant from CMV-positive
      donors. Mean +/- SD follow-up was 430 +/- 157 days (range 178-730 days, median
      449 days). The 6-week ganciclovir regimen prevented neither CMV infection (which
      occurred in 17/21 patients, 81%) nor CMV disease (seen in 8/21 patients, 38%). A
      fourfold rise in CMV antibody titer only preceded the onset of CMV disease in
      3/13 instances (23%). We conclude that a 6-week regimen of ganciclovir
      prophylaxis does not prevent CMV infection or disease in lung transplant
      recipients and that a rise in serially obtained CMV antibody titers rarely
      precedes the development of CMV disease.

PMID- 7732562
TI  - Microchimerism linked to cytotoxic T lymphocyte functional unresponsiveness
      (clonal anergy) in a tolerant renal transplant recipient.
AB  - A patient was found to be functionally tolerant of a maternal kidney allograft as
      evidenced by good graft function 5 years after cessation of all immunosuppressive
      drug therapy. Despite normal in vitro proliferative and IL-2 responses, patient
      anti-donor 1 degree MLR cultures yielded little donor-specific CTL activity in
      either bulk or limiting dilution analysis (LDA) cultures. Using polymerase chain
      reaction, the patient's PBL and skin were found to contain donor-derived Bw6+
      cells. Removal of Bw6+ donor cells from the patient PBL with mAb and
      immunomagnetic beads before stimulation with donor PBL on day 0 failed to restore
      donor-specific CTL in either bulk 1 degree MLR or LDA cultures. Restimulation of
      1 degree cultures with donor stimulator cells plus exogenous IL-2, however,
      completely restored anti-donor HLA class I-specific CTL, indicating class I
      specific CTL precursors were not clonally deleted. Fresh patient PBL, as well as
      donor cell-enriched fractions, when added at the initiation of 3 degrees MLR
      cultures, inhibited the generation of anti-donor CTL, whereas donor cell-depleted
      fractions did not. The inhibition was cell dose-dependent, was specific for the
      anti-donor response, and was radioresistant (1200 rad). Thus, the clinical
      tolerance observed in patients with microchimerism may be due to the presence of
      veto cells within the circulating donor cell pool.

PMID- 7732563
TI  - In vivo depletion of CD8+ T cells results in Th2 cytokine production and
      alternate mechanisms of allograft rejection.
AB  - A current hypothesis states that Th1 cytokines promote allograft rejection and
      that Th2 cytokines promote graft acceptance. We present data that question the
      tolerogenic activity of Th2 cytokines, and we suggest that Th2 cytokines may
      evoke allograft rejection by recruitment of alternate effector mechanisms.
      Unmodified rejection of mouse heterotopic cardiac allografts is associated with
      the accumulation of large numbers of donor-reactive CD8+ CTL within the
      allograft, which is indicative of a Th1-driven cellular response. However, when
      recipients are depleted of CD8+ CTL, rejection still occurs and is associated
      with an aggressive cellular infiltrate rich in eosinophils, large mononuclear
      cells, and fibroblast-like cells. Eosinophils, which are responsive to the Th2
      cytokines IL-4 and IL-5, are not present in unmodified rejecting allografts.
      Differential production of Th1 versus Th2 cytokines was further suggested by
      altered levels of IgG2a (promoted by IFN gamma) and IgG1 (promoted by IL-4)
      alloantibody in the sera of these mice; IgG2a dominated the alloantibody response
      in unmodified allograft recipients, whereas IgG1 levels increased in recipients
      depleted of CD8+ CTL. Altered intragraft cytokine gene expression was verified by
      RT-PCR; Th1 (IL-2, IFN gamma), but not Th2 (IL-4, IL-5, IL-10), cytokine mRNAs
      were readily detectable in the allografts of unmodified recipients. In contrast,
      both Th1 and Th2 cytokine genes were expressed in the allografts of mice depleted
      of CD8+ CTL. These data suggest that donor-reactive CD8+ CTL inhibit intragraft
      production of Th2 cytokines, thereby promoting a Th1 dominated-rejection
      response. Elimination of CD8+ cells allows Th2 cytokine production, which may
      have deleterious, rather than protective, effects.

PMID- 7732564
TI  - Tolerance induced by direct inoculation of donor antigen into the thymus in low
      and high responder rodents.
AB  - A novel approach to tolerance induction in rats was recently described where
      donor antigen is inoculated directly into the thymus along with a brief period of
      immunosuppression in a pretransplant strategy. To develop a strategy that has
      more clinical appeal, we evaluated the timing of donor antigen inoculation in
      relation to allografting, the use of frozen bone marrow as the antigen, and the
      dose response of purified T cells as the antigen in a low responder heterotopic
      heart allograft combination. Additionally, the success of this pretransplant
      strategy in different low and high responder strain combinations was defined. In
      tolerant low responder animals we evaluated in vitro and in vivo cellular
      immunity. Tolerant host strain naive CD8+ T cell responses to donor and third
      party stimulators were compared to determine if tolerance is related to the
      strength of the response of the T cell subsets to donor antigen. Frozen bone
      marrow can induce tolerance in a low responder combination. Additionally, the
      dose of purified T cells necessary for tolerance induction was 5 x 10(5) cells.
      The pretransplant strategy was successful in two low responder strain
      combinations, Lewis into Wistar Furth and Lewis into DA, but unsuccessful in all
      high responder strain combinations evaluated. Low responder animals unresponsive
      to donor heart allografts demonstrate intact cell-mediated immunity and donor
      specific tolerance in vivo by rejecting third party but not second donor strain
      hearts. The in vitro responses of tolerant animals demonstrated donor-specific
      suppression of the MHC class II response but an intact (normal) response to third
      party stimulators by proliferation assays and IFN-gamma production, suggesting
      suppression at the CD4+ T cell subset level.

PMID- 7732565
TI  - Newborn baboon serum lacks natural anti-pig xenoantibody.
AB  - Discordant xenotransplantation represents an attractive alternative to
      allotransplantation in light of the shortage of donor organs currently available
      for cardiac allotransplantation. Unfortunately, discordant xenotransplantation is
      still limited by hyper-acute rejection, a process thought to be mediated by
      natural anti-xenodonor antibody. Based on data that cytotoxic natural
      xenoantibodies are IgM in nature, we postulated that natural xenoantibodies may
      be absent from newborn serum. Baboon sera were collected from infant baboons.
      Pooled adult baboon sera were used as controls. A whole cell ELISA was performed
      to determine the binding of xenoantibodies to pig aortic endothelial cells and
      pig lymphocytes. The cytotoxicity of both adult and newborn baboon sera to pig
      aortic endothelial cells was measured by a MTT (3-(4,5-dimethyl-thiazoyl-2-y) 2,5
      diphenyl-tetrazolium bromide) assay. Newborn baboon sera demonstrated very low
      levels of binding of natural IgM xenoantibodies to pig endothelial cells and
      lymphocytes, whereas natural IgM xenoantibodies from adult baboon sera bound
      significantly to both pig aortic endothelial cells and lymphocytes. IgG natural
      antibodies in both adult and newborn sera bound to pig endothelial cells and pig
      lymphocytes. The MTT assay demonstrated high levels of cytotoxicity to pig
      endothelial cells from adult baboon sera and very low levels of cytotoxicity from
      newborn baboon sera. In this study, newborn baboon sera were demonstrated to be
      free of natural IgM xenoantibodies to pig endothelial cells and lymphocytes.
      Although natural anti-pig IgG antibodies were present in newborn sera, newborn
      baboon sera lack cytotoxicity to pig target cells. These findings suggest that
      IgM is the more important xenoantibody and that hyperacute rejection of
      discordant cardiac xenografts may be avoidable in the newborn.

PMID- 7732566
TI  - Comparative polyclonal antithymocyte globulin and antilymphocyte/antilymphoblast
      globulin anti-CD antigen analysis by flow cytometry.
AB  - Polyclonal antithymocyte globulin (ATG)/antilymphocyte and antilymphoblast
      globulins (ALG) antibodies have been used successfully in transplantation,
      aplastic anemia and graft-versus-host disease. Flow cytometry has been used to
      analyze peripheral blood lymphocyte populations in transplant patients receiving
      polyclonal ATG/ALG preparations for immunosuppression. Recent reports have
      indicated clinical dose adjustment based on levels of patient's cells expressing
      various CD antigens. In vitro analysis of individual polyclonal ATG/ALG CD
      antigen specificity could identify appropriate antigens for clinical monitoring
      as well as provide useful in vitro activity data. Therefore, a flow cytometry
      based assay to characterize and compare activities to specific CD antigens found
      on the surface of peripheral blood lymphocytes has been developed. Activities
      found in four lots each of horse ATG (ATGAM, Upjohn), rabbit and horse ATG
      (thymoglobulin and lymphoglobulin, Merieux), horse ALG (Minnesota), and rabbit
      ATG (Fresenius) have been compared for CD2, CD3, CD4, CD5, CD7, CD8, CD11a, CD18,
      CD28, CD44, CD45, and TCR-alpha/beta antigens. Quantitation is achieved by
      measuring the concentration of ATG/ALG required to give 50% inhibition of antigen
      specific fluorescent-labeled monoclonal antibody relative to buffer controls. The
      three horse products tested have similar activity to most antigens tested.
      However, Fresenius rabbit ATG has the lowest activity for almost all antigens
      tested whereas the Merieux rabbit ATG has activities closer to the horse
      products. This technique allows for rapid in vitro comparison of reactivities to
      individual lymphocyte antigens as well as in vitro analysis of consistency.

PMID- 7732567
TI  - Unconventional rejection of neural retinal allografts implanted into the
      immunologically privileged site of the eye.
AB  - The unique feature of neural transplantation in the central nervous system is
      that the graft is derived from and implanted into an immunologically privileged
      site. The eye, as a part of the central nervous system, normally maintains an
      immunosuppressive microenvironment in which alloantigens induce an active down
      regulation of specific delayed hypersensitivity. To determine whether neural
      retinal allografts are eventually rejected and, if so, what type of immunity is
      associated with rejection, we implanted allogeneic and syngeneic newborn neural
      retinal grafts into the anterior chamber of the eyes of immune-competent mice. In
      addition, similar allografts were implanted into severe combined immune-deficient
      (SCID) mice. The fate of these grafts was determined by clinical and histological
      examination. At post-implantation day 12, all allogeneic and syngeneic grafts
      survived comparably well with no evidence of inflammation. At post-implantation
      day 35, the syngeneic grafts in the immune-competent mice and the allogeneic
      grafts in the SCID mice continued to thrive, whereas the allografts in the immune
      competent mice were remarkably reduced in size and had lost the organization of
      their retinal cell layers. Interestingly, these grafts' deterioration occurred
      with no obvious cellular infiltration. When systemic graft-specific immunity was
      examined, it was found that delayed hypersensitivity was impaired at post
      implantation day 12 in allograft recipients. However, by post-implantation 35 day
      when deterioration was detected in these grafts, suppression of immunity was
      replaced by vigorous delayed hypersensitivity. These results suggest that
      intraocular retinal allografts eventually succumb to rejection and that rejection
      is correlated with the emergence of donor-specific delayed hypersensitivity. The
      possible relationships of atypical, chronic rejection of intraocular neural
      retinal allografts to emergent delayed hypersensitivity are discussed.

PMID- 7732568
TI  - Renal allograft rejection in a patient with the Wiskott-Aldrich syndrome.

PMID- 7732569
TI  - Case report: reversal of left ventricular systolic dysfunction after renal
      transplantation in a patient with a diabetic nephropathy.

PMID- 7732570
TI  - Effector cells must recognize antigens expressed in the graft to cause efficient
      skin graft rejection in SCID mice.

PMID- 7732571
TI  - Regulators of cell death.
AB  - A novel oncogene-derived protein, Bcl-2, functions as a repressor of cell death
      in a genetic pathway of cellular suicide that appears to be common to all
      multicellular animals. A related protein that promotes cell death, Bax, wrestles
      with Bcl-2 through conserved motifs, BH1 and BH2, establishing a set point for
      these deaths. In Bcl-2-deficient mice, the ratio of these molecules is reset,
      resulting in massive cell death in several cell types.

PMID- 7732572
TI  - Nuclear factors in sevenless signalling.
AB  - Recent studies in both vertebrates and invertebrates support an 'hourglass' model
      for signal transduction from receptor tyrosine kinases: Ras channels signals from
      diverse receptor tyrosine kinases into a common cytoplasmic kinase cascade, the
      targets of which are an even more diverse collection of nuclear proteins. What
      are these nuclear factors, and how do they interact to direct specific cellular
      responses to a generic signal? The past year has brought considerable progress in
      our quest to answer these questions in one model genetic system, the Drosophila
      eye.

PMID- 7732573
TI  - Insights into lymphocyte development from X-linked immune deficiencies.
AB  - The genetic immune deficiencies have drawn the attention of physicians and
      immunologists for more than 40 years. The selectivity of these deficiencies
      brings into focus the contribution of the response of each arm of the immune
      system to specific pathogens. Recently, the genes underlying four X-linked
      defects in immune development in humans have been identified by either positional
      cloning or candidate-gene cloning techniques. Remarkably, these genetic defects
      reveal a microcosm of lymphocyte developmental controls involving cell-cell
      interactions, combinatorial cell surface receptor specificity and lineage
      specific signal transduction.

PMID- 7732574
TI  - Getting the message: identifying transcribed sequences.

PMID- 7732575
TI  - Alarms and diversions: the biochemistry of development.
AB  - In considering biochemical aspects of development over a range of different
      organisms--plants, animals, fungi and bacteria--some ubiquitous themes emerge.
      Many of the regulatory mechanisms being discovered in higher organisms have
      already been found in yeast, and there are examples of similar mechanisms in
      bacteria, notably, analogies and even homologies in multistep cascades involving
      phosphorylation and negatively acting steps; interplay between development and
      the cell cycle; and emerging evidence that metabolic pathways can be important
      developmental agents. On the other hand, those topics that remain resolutely
      organism-specific may serve as a warning to those who tend to overgeneralize, or
      as the nucleus for the next generation of general insights.

PMID- 7732576
TI  - Was there a single ancestral cereal chromosome?

PMID- 7732577
TI  - Two protocols for nonradioactive in situ hybridization to Xenopus oocytes.

PMID- 7732578
TI  - Death before birth: clues from gene knockouts and mutations.
AB  - A survey of mouse gene knockouts, transgene insertions and spontaneous mutations
      that are lethal prenatally reveals that surprisingly few developmental
      disturbances lead to death of the embryo and early foetus. These disturbances
      include failure to establish and maintain a vascular circulation, and failure to
      make the transition from yolk-sac-based to liver-based haematopoiesis. The embryo
      must also establish gestation-dependent routes of nutritional interaction with
      the mother, including implantation, formation of a yolk-sac vascular circulation,
      and formation of a chorioallantoic placenta. A number of embryonic organ and body
      systems, including the central nervous system, gut, lungs, urogenital system and
      musculoskeletal system, appear to have little or no survival value in utero.

PMID- 7732579
TI  - Gene number, noise reduction and biological complexity.
AB  - Preliminary estimates suggest that gene number, and hence biological complexity,
      increased suddenly at two periods of macroevolutionary change (the origin of
      eukaryotes and the origin of vertebrates), but otherwise remained relatively
      constant. As the genome is in constant flux, what normally constrains the number
      of different genes that an organism can retain? Here, I suggest that an important
      limitation on gene number is the efficiency of mechanisms that reduce
      transcriptional background noise. The appearance of both eukaryotes and
      vertebrates coincided with novel mechanisms of noise reduction.

PMID- 7732580
TI  - Molecules and morphology: where's the homology?

PMID- 7732581
TI  - Gatecrashers at the catalytic party.

PMID- 7732582
TI  - More good sense.

PMID- 7732583
TI  - More good sense.

PMID- 7732584
TI  - More good sense.

PMID- 7732585
TI  - G and C accumulation at silent positions of codons produces additional ORFs.

PMID- 7732586
TI  - Coloured microparticles for clear visualization of agarose beads and plugs.

PMID- 7732587
TI  - Automatic separation of two PCRs in one tube by annealing temperature.

PMID- 7732588
TI  - A modified medium for efficient electrotransformation of E. coli.

PMID- 7732589
TI  - Rapid fluorescence in situ detection of heterologous expression in E. coli and
      counterstaining with diamidinophenylindol.

PMID- 7732590
TI  - Trans-splicing and polycistronic transcription in Caenorhabditis elegans.
AB  - Caenorhabditis elegans engages in three distinct versions of nuclear pre-mRNA
      splicing: cis-splicing of introns and two kinds of trans-splicing that result in
      the addition of two different spliced leaders onto mRNAs. One leader (SL1) is
      used near the 5' ends of pre-mRNAs while the other (SL2) is used at internal
      trans-splice sites of polycistronic pre-mRNAs. Here, I consider how these three
      types of splicing event are faithfully carried out.

PMID- 7732591
TI  - Cell-cycle regulators and cancer.
AB  - Cancer is a disease characterized by loss of cellular growth control. As such, it
      is not surprising that the molecular machinery of the cell cycle is involved in
      tumorigenesis. Recent discoveries have brought several cell-cycle regulators into
      sharp focus as factors in human cancer. Among the most conspicuous types of
      molecule to emerge from ongoing studies in this field are the cyclin-dependent
      kinase inhibitors such as p16. These molecules have several hallmarks of tumor
      suppressors and are perfectly positioned to regulate critical decisions in cell
      growth. The P16 gene appears to be a particularly significant target for mutation
      in sporadic tumors and in at least one form of hereditary cancer.

PMID- 7732592
TI  - Recent human germ-line mutation: inferences from patients with hemophilia B.
AB  - The gene encoding factor IX has a unique number of advantages for studying human
      germ-line mutations. Detailed analyses of the observed mutations of this gene,
      with special attention to the biases in the data, have provided information on
      mutational hotspots (including 'cryptic' dinucleotide repeats), mutation rates
      per base pair per generation, and the sex ratios of mutation. The evidence
      strongly suggests that the great majority of germ-line mutations result from
      endogenous processes, rather than exogenous mutagens. Perhaps nature does not
      permit environmental control of such an important process. Instead, the rate of
      germ-line mutation is placed under selective pressure, of which early-onset
      cancer may be an important mediator.

PMID- 7732593
TI  - Being fruitful: genetics of reproduction in Arabidopsis.
AB  - Reproduction in flowering plants requires a series of interactions between the
      haploid and diploid phases of the life cycle of the plant. Mutations that affect
      these interactions have been identified in Arabidopsis, thus giving insight into
      the processes of gamete development and pollination. These studies promise to
      yield new information on diverse topics in plant biology, from cell-cell
      recognition to the evolution of mating interactions.

PMID- 7732594
TI  - Embryonic development of the larval body wall musculature of Drosophila
      melanogaster.
AB  - The somatic, or body wall, muscles of the larva of Drosophila melanogaster are
      composed of an elaborate pattern of segmentally repeating fibers that form during
      embryogenesis. The primordia of these muscles progress from morphologically
      indistinct mesodermal cells to multinucleate syncytia with unique characteristics
      that include shape, size, location and attachment to the epidermis. Although
      relatively little is known about the development of the musculature and the
      mechanisms by which this elaborate pattern is achieved, recent progress has begun
      to reveal key players in this process.

PMID- 7732595
TI  - The dance of the growth cones--where to next?
AB  - Axon guidance in the developing nervous system is accomplished by a remarkable
      structure, the axon growth cone. This structure navigates, often over long
      distances, to find and synapse with target cells. Transformation of the growth
      cone to a terminal arbor establishes functional circuitry. The navigational
      properties of growth cones, and their interactions with target tissue, have been
      studied widely by examining individual cells in vitro, and have also been
      inferred from histological sections. Recent advances in labelling techniques and
      imaging of living cells have enabled direct observation of the growing axon tip
      in intact embryos as well as in slice preparations. To understand how pathways
      and terminal arbors are formed, the challenge now is to relate the dynamic
      morphology and behaviour of living growth cones to surrounding cues in the
      complex environment of the developing embryo.

PMID- 7732596
TI  - Recent advances in the pharmacology of Ca2+ and K+ channels.

PMID- 7732597
TI  - Inverse agonism: pharmacological curiosity or potential therapeutic strategy?

PMID- 7732598
TI  - Risks in combination therapy of antidepressant drugs.

PMID- 7732599
TI  - NO, nitrosonium ions, nitroxide ions, nitrosothiols and iron-nitrosyls in
      biology: a chemist's perspective.
AB  - The multiplicity of biological functions thus far attributed to NO has led to
      suggestions that some effects might be mediated by other, related species
      instead. The radical nature of NO cannot account for its cytotoxicity, but its
      reaction with superoxide to form peroxynitite and highly reactive hydroxyl
      radicals may be important in this context. The ease with which NO can react with
      and destroy Fe-S clusters is also an important factor. Nitrosonium and nitroxide
      ions can be produced in vivo and will react under conditions that are
      physiologically relevant. Both could, in theory, serve in cell signalling or as
      cytotoxic agents. More direct experimental evidence for their involvement is
      needed before we can confidently assign them specific biological roles. In this
      article, Anthony Butler, Frederick Flitney and Lyn Williams discuss the chemistry
      of NO and related species.

PMID- 7732600
TI  - Endothelium-dependent hyperpolarization: a role in the control of vascular tone.
AB  - Endothelial-dependent relaxation of vascular smooth muscle cells evoked by a
      number of agonists, including cholinomimetics and substance P, is often
      accompanied by an increase (repolarization and/or hyperpolarization) in the
      membrane potential. This change in membrane potential appears predominantly to
      reflect the action of an endothelial-derived hyperpolarizing factor (EDHF), which
      is distinct from NO (or endothelial-derived relaxing factor), and is discussed in
      this article by Chris Garland and colleagues. In large conducting arteries, EDHF
      may provide a secondary system to NO, which assumes primary importance in some
      disease states such as pulmonary hypertension and atherosclerosis. However, in
      small resistance arteries (100-300 microns), EDHF appears to be a major
      determinant of vascular calibre under normal conditions, and may therefore be of
      primary importance in the regulation of vascular resistance.

PMID- 7732601
TI  - Experimental headache models in animals and humans.

PMID- 7732602
TI  - Left ventricular size following shunt operation in tetralogy of Fallot.
AB  - This study was performed in 24 patients with tetralogy of Fallot in whom shunt
      operation was performed instead of total correction because of small left
      ventricular end-diastolic dimension. Left ventricular end-diastolic dimension was
      measured using M-mode and two-dimensional echocardiography pre- and at least one
      year postoperatively. There was no change in the postoperative left ventricular
      size in two patients. However, in the other 22 patients, the left ventricular
      dimension was increased to 70 to 103 percent of normal left ventricular size.
      According to the findings of this study, we can conclude that the patients in
      whom shunt operation was performed would most likely have an increased left
      ventricular size over time.

PMID- 7732603
TI  - Application of ice water to the face in initial treatment of supraventricular
      tachycardia.
AB  - Supraventricular tachycardia (SVT) is a life-threatening dysrhythmia in
      childhood. Initial treatment includes classic vagal maneuvers, some
      pharmacological agents, cardioversion and application of ice water to the face.
      In this paper we report our results of ice water application to the face in SVT.
      The study included ten patients between the ages of seven days and 15 years who
      were admitted to our hospital with supraventricular tachycardia in the previous
      year. Ice water was applied to their faces for five seconds immediately and all
      of them were digitalized. This procedure was utilized in 28 out of 36 SVT
      attacks, and was found to be effective in restoring sinus rhythm on 27 of 28
      occasions (96%). Tachycardia recurred a total of 18 times in three of the ten
      patients. There was no recurrence in six patients. No response was noted in only
      one patient. Application of ice water to the face is an easy, safe, effective and
      repeatable procedure in the initial treatment of supraventricular tachycardia.

PMID- 7732604
TI  - The effects of naltrexone in autistic children: report of two cases.
AB  - This paper reports the observations associated with a brief course of
      administration of naltrexone (NTX) to two autistic children. One male and one
      female child, aged 5.3 and 4.4, respectively, completed the trial. The children
      were placed on NTX for two weeks for six administrations. The dose was 0.5 mg/kg.
      The Behavior Summarized Evaluation and Childhood Autism Scale were completed by
      the teacher and the social worker for baseline and post-experimentation
      observations. The patients' parents were asked to fill out the Parental
      Satisfaction Survey. Although the literature indicates that NTX is effective in
      some children, our observations confirm that NTX is effective in the two cases
      with different degrees of severity of disease.

PMID- 7732605
TI  - Serum carnitine, beta-hydroxybutyrate and ammonia levels during valproic acid
      therapy.
AB  - This study was performed in order to determine the effects of valproic acid on
      serum free carnitine, beta-hydroxybutyrate and blood amamonia. Serum free
      carnitine, beta-hydroxybutyrate and blood ammonia levels were measured in 24
      epileptic children and in 24 age and sex-matched controls. The mean serum free
      carnitine level was significantly lower in patients taking valproic acid (33.5 +/
      13.1 nmol/ml) than in control subjects (50.8 +/- 14.6 nmol/ml) (p < 0.001). The
      mean blood ammonia level was significantly higher in patients receiving valproic
      acid (93.9 +/- 20.5 micrograms/dl) than in controls (79.6 +/- 21.4 micrograms/dl)
      (p < 0.002). The mean serum beta-hydroxybutyrate level was significantly lower in
      patients taking valproic acid (2.26 +/- 2.24 mg/dl) than in controls (4.38 +/-
      2.43 mg/dl) (p < 0.001).

PMID- 7732606
TI  - Transplantation of hematopoietic progenitor cells with emphasis on the results in
      children.
AB  - Attempted human allogeneic marrow transplants in the 1950's and 60's were largely
      unsuccessful. In the past two decades the probability of success has improved
      steadily depending on the type and stage of disease. All marrow transplant teams
      have observed that the results for children are better than for adults. Long-term
      survival and apparent cure rates range from about 90 percent for non-malignant
      diseases transplanted early to 15 percent for patients with advanced leukemia.
      Most marrow transplants have involved an HL-A matched sibling donor but, more
      recently, through the worldwide marrow donor registries a matched unrelated
      volunteer marrow donor can be found for many patients without a family donor.
      Current research involves new preparative regimens for elimination of malignant
      cells, better prevention of graft-versus-host disease (GVHD), and the use of
      hematopoietic growth factors and cytokines. Autologous transplants, which use the
      patient's own marrow, are increasing. The hematopoietic stem cell, which is
      responsible for marrow regeneration after a transplant, has been isolated and
      characterized. Stem cells for transplantation can now be obtained from the
      peripheral blood after mobilization of these cells by chemotherapy or
      hematopoietic growth factors.

PMID- 7732607
TI  - Eosinophilic gastroenteritis presenting as protein--losing enteropathy (case
      report).
AB  - Eosinophilic gastroenteropathy is an uncommon, idiopathic disease in children
      that is characterized by eosinophilic inflammation of the intestine. Predominant
      involvement of the mucosa is associated with diarrhea and less commonly
      gastrointestinal protein and fat malabsorption. A seven-year-old female was
      diagnosed with eosinophilic gastroenteritis. This condition was proven by
      biopsies attained through an endoscope. The most common symptoms were abdominal
      pain, diarrhea and edema. The patient had no eosinophilia. Her serum
      immunoglobulin E level was increased (1590 mg/dl). Barium studies revealed
      mucosal thickening of the antrum, distal jejunum and proximal ileum and prominent
      mucosal folds of the colon. Ultrasound examination revealed thickening of the
      colonic wall. The patient was treated with prednisolone (2 mg/kg/day). The
      symptoms subsided and serum immunoglobulin E decreased to 500 mg/dl 45 days
      later. The patient is being followed with a small maintenance dose of
      prednisolone with no relapse.

PMID- 7732608
TI  - Tay-Sachs disease: a case report.
AB  - Tay-Sachs disease (GM2 gangliosidosis I) is an autosomal recessive lysosomal
      storage disorder confined to the central nervous system, resulting from
      deficiency of hexosaminidase A. The case presented is of a twelve-month-old girl
      brought to the hospital because of mental-motor deterioration and convulsions.
      She was the child of first cousins and had a history of the deaths of two
      siblings with the same manifestations. Generalized hypotonia, macrocephaly,
      hyperacusis and a retinal cherry red spot appearance were present. There was no
      organomegaly. The diagnosis of Tay-Sachs disease was made by means of absence of
      serum hexosaminidase A activity.

PMID- 7732609
TI  - Nonketotic hyperglycinemia in a newborn infant.
AB  - A neonate with nonketotic hyperglycinemia who experienced apnea, hiccups and
      tonic-clonic seizures on the first day of life is reported. The physical findings
      and laboratory tests including arterial blood gases were normal. However, serial
      blood and CSF amino-acid analyses demonstrated elevated glycine levels. Serum and
      CSF glycine levels were 1949 mumol/L and 415.5 mumol/L, respectively. (Normal
      serum level is 104-254 mumol/L and CSF level is 5 +/- 2 mumol/L). The CSF/plasma
      glycine ratio was 0.11. Oral sodium benzoate and folic acid therapy was
      initiated. After two weeks of assisted ventilation and clinical improvement, the
      patient was discharged with a protein-restricted diet.

PMID- 7732610
TI  - Hypophosphatasia in a newborn infant.
AB  - Infantile type hypophosphatasia, an autosomal recessive disease with severe
      clinical manifestations, is characterized biochemically by subnormal activities
      of circulating alkaline phosphatase. In this report, we presented a five-day-old
      male with this rare disorder. His parents were first cousins, and he was first
      seen for jaundice. He had soft calvaria, large fontanel, extremely wide cranial
      sutures, low-set ears, a depressed nasal bridge, funnel chest, and short and
      bowed distal limbs. Roentgenographic studies showed widened sutures and poor
      ossification of the skull, bowing of the femora and slight modeling defects in
      the long bones. A low serum alkaline phosphatase activity led us to measure
      excretion of phosphoethanolamine and found it to be increased.

PMID- 7732611
TI  - Gangrene after penicillin injection (a case report).
AB  - A patient with right lower limb gangrene that developed after penicillin
      injection is presented. Accidental intraarterial administration of penicillin may
      cause gangrene necessitating amputation. To avoid this severe complication, every
      intramuscular injection should be given with meticulous attention to proper
      technique, with adequate restraint of the patient, and with full knowledge of
      local anatomy and potential complications.

PMID- 7732612
TI  - Renal replacement therapies for critically ill pediatric patients.
AB  - It could be a great challenge for a nephrologist to prescribe a renal replacement
      therapy for a critically ill, hemodynamically unstable pediatric patient.
      Intermittent hemodialysis and peritoneal dialysis frequently fall short of being
      an optimal renal replacement therapy for such a patient. Continuous
      hemofiltration is offering new alternatives that can deliver sufficient clearance
      to meet the needs of a critically ill child. High fluid intake required for total
      parenteral nutrition and medications can easily be fulfilled by these modalities
      without compromising the cardivascular system. Of these techniques, continuous
      veno-venous hemofiltration is superior to continuous arterio-venous
      hemofiltration because it delivers a consistent ultrafiltration rate dependent on
      pump-driven blood flow and does not require the insertion of a large-bore
      catheter into an artery. Thus, various modalities of hemofiltration can offer an
      alternative to the critically ill child with acute renal failure.

PMID- 7732613
TI  - Fatal agranulocytosis developed in the course of carbamazepine therapy. A case
      report and review of the literature.
AB  - A case of fatal agranulocytosis in an adolescent who was on carbamazepine therapy
      is presented. The clinical and laboratory findings suggest that the primary cause
      of the disorder was neutropenia rather than infection, and the preceding factor
      for neutropenia was carbamazepine. The timing of occurrence of the hematologic
      picture, its dependency on dose increments, and the lack of symptoms until
      infection supervened are consistent with an idiosyncratic-toxic drug reaction
      (type 2 drug reaction). This is the first reported agranulocytosis case due to
      crabamazepine in adolescence.

PMID- 7732615
TI  - [Problematic health expenditures for social security].

PMID- 7732614
TI  - A case report of penis reconstruction for partial penis necrosis following
      circumcision.
AB  - Circumcision is one of the most common operations performed world-wide and is
      usually done for religious and social reasons. Although it is a simple procedure,
      serious complications may result. These complications may range from hemorrhage
      to total amputation. Reconstruction of a partial amputation of phallus due to
      circumcision by full-thickness skin grafting is presented in this paper.

PMID- 7732616
TI  - [Health expenditure and health status].

PMID- 7732617
TI  - [Health care financing and the system of health coverage in Tunisia].

PMID- 7732618
TI  - [Reform of the health insurance system in Tunisia].

PMID- 7732619
TI  - Immobilizing and imaging microtubules by atomic force microscopy.
AB  - Microtubules isolated from pig brains have been immobilized on an inorganic
      substrate for use in AFM studies. The method employs 4
      aminobutyldimethylmethoxysilane and glutaraldehyde to activate a silicon wafer
      for binding the biopolymer. The covalent bond ensures the positional stability of
      the tubules on the substrate, and allows reproducible scanning probe experiments.
      Microtubules have been imaged both by atomic force and scanning tunneling
      microscopy, yielding results very similar to electron microscopy. The average
      apparent height of the tubules is smaller than observed with transmission
      electron microscopy (25 nm) and is smaller in buffer solution (10 nm) than in air
      (15 nm). The biopolymer surface is softer under buffer than in air. The highest
      resolution was obtained with the tapping mode where surface features as small as
      10 nm in X and Y have been resolved. Gold-coated tubules bound on silicon have
      been successfully imaged by STM, while images of uncertain origin were generated
      for tubules deposited on graphite. It is shown that artefacts imaged on a blank
      graphite surface can easily be confounded with collapsed tubules.

PMID- 7732620
TI  - A method for 2D crystallization of soluble proteins at liquid-liquid interface.
AB  - Two-dimensional crystals of soluble proteins were formed at the interface between
      an aqueous solution of proteins and a thin organic liquid (dehydroabietylamine).
      Proteins were adsorbed to the interface from the aqueous side and formed a two
      dimensional crystal under suitable conditions. This method offers the advantage
      of great surface mobility and ideal homogeneity. Furthermore, the positive charge
      attracted negatively charged proteins well to the interface and no denaturation
      of the proteins was observed. With this technique, two-dimensional crystals of
      ferritin, catalase, chaperonin and 50S ribosome were prepared and their
      structural features were determined.

PMID- 7732621
TI  - [Neutral alpha-glucosidase activity in the urine in congenital hydronephrosis in
      children].
AB  - Enzymuria was studied in children who had undergone surgery for congenital
      hydronephrosis. A total of 109 patients were operated on according to Andersen
      Hynes-Kucher with ureteral intubation and pelvic drainage. The course of renal
      tissue tubular function recovery upon elimination of the obstruction in the
      pyeloureteral segment was followed up by urine activity of neutral alpha
      glucosidase as was the enzyme activity dynamics in dysplastic congenital
      hydronephrosis. The latter evidences reduced, but satisfactory functional
      capacity of the operated on organs.

PMID- 7732622
TI  - [Vesicoureteropelvic reflux in pregnant animals and its role in the pathogenesis
      of acute gestational pyelonephritis (experimental research)].
AB  - The experiments on naturally pregnant rats have demonstrated that pregnancy
      contributes to much more frequent occurrence of vesicoureteropelvic reflux (VUPR)
      which, in its turn, is essential for pathogenesis of acute gestational
      pyelonephritis (AGP). Dynamic obstruction of the urine flow as a result of
      reduced function of leiomyocytes of urinary tract muscles, decreased urothelial
      glycocalyx and consequent adhesion of pathogenic agents comprise parts of this
      pathogenesis. The conclusion is made that VUPR pregnant females are at risk to
      develop AGP and should be placed by the urologist on ultrasonic monitoring
      lasting all pregnancy and postpartum periods.

PMID- 7732623
TI  - [The phagocytic test in the assessment of antimicrobial protection in
      inflammatory urologic diseases].
AB  - As shown in in vitro original modelling of red cell action on phagocytic process
      in the whole blood of patients with urological inflammation, these patients have
      increased count of neutrophils involved in phagocytosis, but low specific
      absorption of these neutrophils due to red cells. In chronic renal insufficiency
      characterized by a low phagocytic activity of neutrophils only stimulating
      potential of red cells can be noted.

PMID- 7732624
TI  - [The cell composition and cytoarchitectonic characteristics of the lymphoid
      formations in the kidney pelvis and ureter of adults].
AB  - Quantitative characteristics, cell composition and cytoarchitectonics are
      characterized for lymph nodules in the walls of renal pelvis and ureter according
      to the findings in 14 total autopsied specimens of the pelvis and ureter obtained
      from 7 females and males aged 22-60. All of them had been killed in accidents and
      were free of urogenital, hematological, immune and lymphatic diseases. As
      indicated by histological sections, lymph nodules in the pelvic and ureteral
      mucosa of the examinees did not contain clear reproduction centers. The cells of
      the above lymph nodules comprised primarily small and medium-sized lymphocytes as
      well as reticular cells. Blast cells and macrophages were not numerous and
      averaged 2.6% of the total cell population. The count of cells undergoing
      destruction remained stable and made up from 1.57 +/- 1.6 to 3.52 +/- 2.06%. As
      for cytoarchitectonics, typical for the nodules was the existence of pairs,
      groups and chains of small and medium-sized lymphocytes.

PMID- 7732625
TI  - [The postgraduate education of urologists in the Russian Federation].

PMID- 7732626
TI  - [Plasmapheresis in the treatment of complicated forms of acute suppurative
      pyelonephritis in pregnant women].
AB  - Plasmapheresis was carried out in the course of treatment of 46 19-28-year-old
      females (gestation 13-37 weeks) suffering from complicated acute purulent
      pyelonephritis (APP) versus 50 controls treated conventionally without
      plasmapheresis. Nonconventional scheme included antibacterial therapy, infusions,
      plasmapheresis, surgical interventions. The number of plasmapheresis sessions
      ranged from 3 to 6 per 1 patient depending on APP severity and efficacy of the
      treatment. Plasma removal reached 600-900 ml of plasma per session, a total of
      2000-2600 ml per course of treatment. Introduction of plasmapheresis made it
      easier to manage pyoseptic intoxication, to achieve clinico- laboratory
      remission. The efficacy of treatment increased by 20%.

PMID- 7732627
TI  - [Therapeutic physical exercise before and after an operation on the kidney in
      nephrolithiasis patients].
AB  - As shown by cardiorespiratory investigations, nephrolithiasis patients have
      defects in external respiration and central hemodynamics. These can be corrected
      by specially developed preoperative exercises which are also able to prevent
      postoperative complications. The above preoperative exercises are promoted as a
      part of preoperative preparation and postoperative management of nephrolithiasis
      patients.

PMID- 7732628
TI  - [The hazards and complications of internal drainage of the upper urinary tract].
AB  - The causes, diagnosis, prevention and management of complications arising in
      insertion of internal ureteral stents have been analyzed basing on the results of
      289 procedures in 272 patients. Dangers and complications related to drainage of
      upper urinary tracts (UUT) may be divided into technological (arising when
      inserting or removing the stent) and clinical (arising within the time of the
      stent location in the UUT). Technological complications emerged in 25 cases
      (8.7%). Of them, iatrogenic ureteral perforation occurred most frequently (9
      cases, 3.1%). Clinical complications were registered in 41 patients (14.2%). Most
      common of them were: attacks of pyelonephritis due to vesicoureteral reflux and
      stent impassibility (19 and 9 patients, 6.6% and 3.1%, respectively). To
      ascertain the causes of the stent impassibility for urine, a complex of x-ray and
      ultrasound investigations was applied. The reflux is often provoked by the
      bladder drainage with urethral catheter. In the stent obstruction or concrement
      formation on it, the removal and changes of the stent were combined with
      extracorporeal or contact lithotripsy. Spontaneous distal migration of the stent
      (8 cases) necessitated its transurethral removal. Insertion of inner ureteral
      stents is rarely complicated by spontaneous migration of the drainage above the
      ureteral ostium (1 case) and by development of arterial-ureteral fistula (1
      case). Thorough roentgenoendoscopical control over the stent insertion and
      staying in the UUT assists prevention and treatment of complications consequent
      to UUT internal drainage.

PMID- 7732629
TI  - [The effect of an emulsion containing alpha-tocopherol and dimethylsulfoxide and
      of verapamil on reperfusion injury to the rat kidneys].
AB  - Four series of experiments were made on 82 rats which experienced 90-min renal
      ischemia. Animals from series 1 received no drugs. Animals of series 2 were
      injected i.v. emulsion (10 mg/kg alpha-tocopherol + 200 mg/kg dimethylsulphoxide)
      10 min before ischemia termination. Animals of series 3 received i.v. verapamil
      (0.5 mg/kg) prior to reperfusion. Rats of series 4 were given alpha-tocopherol
      acetate emulsion simultaneously with verapamil. Introduction of alpha-tocopherol
      emulsion significantly inhibited lipid peroxidation (ascorbate-induced
      peroxidation activation) in intact kidneys blocking this activation in the
      reperfusion period. The ischemic kidney function proved much better on ischemia
      day 2 in the 2nd and 4th series. In series 3 the results were similar to control.
      On postischemia day 7 renal function did not differ much between the series.
      Mechanisms of the emulsion protective action and the causes of its absence in
      verapamil are covered in the discussion.

PMID- 7732630
TI  - [Intraoperative hemodynamics in the recipients of kidney allografts from living
      related donors].
AB  - Electromagnetic flowmetry was performed in 53 recipients of kidneys from related
      donors to investigate intraoperative hemodynamics and its relationships with such
      factors as the degree of histocompatibility between the donor and recipient, of
      blood relationship, renal laterality. The real total blood flow was compared to
      proper flow according to Inke formula. The result of this comparison gave
      evidence for angiospasm or vasodilation. The range of real flow was much wider in
      the recipients than in donors. This reflected much more frequent angiospasms and
      vasodilation in the recipients: the transplants displayed angiospasms in 26.2% of
      the cases. The angiospastic patients developed rejection crises 2 times more
      frequently than those without the spasms. It is concluded that intraoperative
      vasoconstriction denotes greater probability to develop rejection crisis in early
      postoperative period.

PMID- 7732631
TI  - [Morphological changes in the kidneys in refluxogenic nephropathy in patients
      with congenital and acquired vesicoureteral reflux].
AB  - Current views of foreign investigators on refluxogenic nephropathy rest on the
      results of pig experiments. The authors studied human material: kidneys of
      children who died of pyelonephritis caused by vesicoureteral reflux. Electron
      microscopic and other morphological examinations of the kidney pelvic wall
      provided evidence for a distinct difference in relevant morphological structures
      observed in congenital versus acquired reflux. Congenital vesicoureteral reflux
      displays a specific morphological picture suggesting congenital refluxogenic
      nephropathy, whereas acquired reflux produces a typical picture of ascending
      pyelonephritis.

PMID- 7732632
TI  - [The treatment results in excretory infertility in men].

PMID- 7732633
TI  - [Microwave hyperthermia and thermotherapy in the treatment of prostatic
      diseases].

PMID- 7732634
TI  - [Interpelvic, ureteropelvic and interureteral anastomoses in duplication of the
      kidney and the ureter].
AB  - The surgery is made to save both halves of the double kidney in mechanic
      obstruction or vesicoureteral reflux in the accessory or basic ureter. The
      affected ureter is always removed under anastomosis. The interventions are
      indicated in anomalies causing ureteral obstruction, ureterohydronephrosis,
      vesicoureteral reflux, pyelonephritis. They are frequently performed in ectopic
      ureterocele of the accessory ureter, in vesicoureteral reflux associated with
      intravesical high ectopy of the basic ureter ostium and normal ostium of the
      accessory ureter, in low intra- and extravesical ectopy of the accessory ureter
      ostium. The authors have conducted 21 operations in 20 patients: bilateral
      transureteroureteral, 2 intrapelvic, 1 ureteropelvic and 18 transureteroureteral
      anastomoses. The surgery was decided upon because of ectopic ureterocele of the
      accessory ureter, ectopic ureterocele of the accessory ureter with vesicoureteral
      reflux via ureterocele, high ectopy of the basic and low ectopy of the accessory
      ureter ostia with reflux, low ectopy of the accessory ureters ostia. Short- and
      long-term outcomes of all the operations were good.

PMID- 7732635
TI  - Sarcocystis fusiformis: some Krebs cycle enzymes in various fractions of
      sarcocysts of buffalo (Bubalus bubalis).
AB  - A biochemical investigation was carried out on the relative presence of some
      enzymes of the Krebs cycle and of the associated energy metabolism in various
      fractions (namely, cyst wall, cyst fluid and zoites) of sarcocysts of Sarcocystis
      fusiformis from the oesophageal muscles of naturally infected Indian water
      buffalo (Bubalus bubalis). Except for malate dehydrogenase, the activities of
      aconitase, isocitrate dehydrogenase, succinate dehydrogenase and fumarase were
      beyond detectable limits, pointing to a non-functional Krebs cycle in the cysts
      of this parasite. The activities of adenosine triphosphatase and cytochromes were
      lowest in cyst fluid and were maximally depicted by cyst wall and zoites.

PMID- 7732636
TI  - Interactions between Ostertagia ostertagi and Cooperia oncophora in calves.
AB  - Development of immunity to Ostertagia ostertagi and Cooperia oncophora and
      interactions between both species in primed calves were investigated after
      homologous, heterologous and concurrent challenge infections. Worm counts, faecal
      egg output, IgG1 and IgG2 antibodies and the presence of globule leucocytes were
      used to evaluate the possible interactions. Results show that immunity build-up
      against O. ostertagi is slow in comparison with C. oncophora. The presence of
      early fourth-stage larvae and globule leukocytes in the O. ostertagi primed
      groups was significantly different to that of a previously uninfected control
      group. Ostertagia ostertagi and C. oncophora IgG1 antibodies were high in the
      previously exposed groups compared with uninfected controls and C. oncophora
      antibodies cross-reacted strongly with O. ostertagi antigens. There was no
      conclusive evidence for an interaction between C. oncophora and O. ostertagi.
      Globule leukocytes, IgG1 antibodies and early fourth-stage larvae seem to be
      related to development of immunity to O. ostertagi.

PMID- 7732637
TI  - Strongyle infections in sheep and goats under the traditional husbandry system in
      peninsular Malaysia.
AB  - Faecal egg counts were used to study patterns of trichostrongyle infections in
      sheep and goats according to season, age, pregnancy and lactation on traditional
      farms in west Malaysia. Haemonchus contortus and Trichostrongylus spp. were the
      most important strongyles in sheep and in goats, H. contortus, Trichostrongylus
      spp. and Oesophagostomum spp. were most prevalent. The faecal egg counts of sheep
      and goats were apparently not influenced by the small seasonal climatic
      variations. Strongyle infections were acquired at an earlier age in sheep than in
      goats. Mean faecal egg counts decreased from the age of 8 months onwards in sheep
      while in goats this occurred from 12-18 months onwards. A periparturient rise in
      strongyle egg counts was observed in both animal species. Haemonchus contortus
      was mainly responsible for this rise in faecal egg counts. The results are
      discussed with reference to control of gastrointestinal strongyle infections in
      sheep and goats.

PMID- 7732638
TI  - Dry areas: an example of seasonal evolution of helminth infection of sheep and
      goats in southern Mauritania.
AB  - A total of 647 faecal egg counts and 53 necropsies were performed on sheep and
      goats originating from three sites of a Sahelian region of Mauritania (Gorgol)
      over a period of 2 years (1990-1992). Haemonchus contortus, Oesophagostomum
      columbianum and Stilesia globipunctata were the most prevalent species. The
      seasonal pattern was characterized by long survival of adults and high
      percentages of arrested fourth-stage larvae in the dry season, suggesting that
      two different strategies were used to survive from one rainy season to the next.
      Sheep and goats were equally infected, except for Stilesia globipunctata, which
      was found more often in sheep. The influence of age was limited, although kids
      and lambs born in the beginning of the dry season did not become infected until
      their first grazing in the rainy season.

PMID- 7732639
TI  - Isotype-specific serum antibody responses of sheep to Haemonchus contortus
      antigens.
AB  - In total, 19 8-month-old Texel sheep were used to study the isotype-specific
      serum antibody responses against infective larvae and adult worms of Haemonchus
      contortus. Group Group 1 sheep (n = 7) were infected with 20,000 L3 larvae (Week
      0), treated with ivermectin 6 weeks post-infection and subsequently challenged at
      Week 10 of the experiment. This challenge consisted of a trickle infection of
      10,000 L3 larvae per week for 5 weeks. Group 2 sheep (n = 7) received a single
      infection at Week 10 of the experiment, and Group 3 (n = 5) served as a non
      infected control group throughout the entire experiment. Individual blood and
      faeces samples were collected at weekly intervals. The immune responses were
      monitored by ELISA and Western blotting. The secondary immune response coincided
      with a significant reduction of the Haemonchus egg output and reduction of worm
      counts. Both primary and challenge infections induced humoral immune responses,
      and ELISA revealed that the most dominant serum antibody responses belong to the
      IgG1 isotype and to a lesser extent to IgG2. IgM and IgA responses were less
      dominant. Western blotting experiments demonstrated that many antigens were
      commonly recognized by antibodies from both primary and challenge infected
      animals. However, sera of immune animals specifically reacted with low molecular
      weight proteins. In particular, a 24 kDa antigen present in adult worms appeared
      to be specifically recognized.

PMID- 7732640
TI  - Effects of dietary protein intake on responses of young sheep to infection with
      Trichostrongylus colubriformis.
AB  - The effects of protein supplementation and infection with Trichostrongylus
      colubriformis on production responses and immune function in young sheep and on
      nematode population dynamics were assessed. Eighty-four 3-month-old Merino wether
      sheep were housed in individual pens and fed ad libitum chopped oaten hay
      containing 0.5% urea, together with 50 g day-1 lucerne meal. Fish meal (FM) was
      given as a source of protected protein at 0, 50 or 100 g day-1 (FM0, FM50, FM100;
      from Days --28 to 140). From Days 1 to 140, 0 or 1000 T. colubriformis infective
      larvae were given on Mondays, Wednesdays and Fridays. Infected sheep were
      slaughtered after 35, 70, 105, or 140 days of infection. Live-weight gain was
      reduced significantly by infection with T. colubriformis in sheep given FM0, but
      not in sheep given FM50 or FM100. Greasy wool production and fibre diameter were
      increased by FM, whereas the effects of infection with T. colubriformis on wool
      measurements depended on the level of FM given. Worm egg concentrations in faeces
      were significantly lower for sheep given FM100 than for those given FM0 or FM50
      during the last 28 days of infection. Similarly, the apparent rate of worm
      expulsion was considerably higher in sheep given FM than in those not given FM.
      The rate of expulsion of T. colubriformis correlated with levels of circulating
      eosinophils as well as with the concentration of intestinal sheep mast cell
      proteases. Levels of parasite-specific and non-specific circulating antibodies
      were either unaffected or reduced as a result of supplementation with FM,
      although lymphocyte stimulation in vitro in response to T. colubriformis third
      stage larval antigen was enhanced significantly in infected animals given FM100.
      It was concluded that supplementary feeding with FM substantially reduced the
      production losses attributable to infection with T. colubriformis and was
      associated with enhanced expulsion of the parasite burden.

PMID- 7732641
TI  - Influence of dietary aflatoxin on Eimeria uzura infection in Japanese quail
      (Coturnix coturnix japonica).
AB  - A study was conducted to assess the influence of dietary aflatoxin on Eimeria
      uzura in Japanese quail (Coturnix coturnix japonica). Quail receiving 1 part per
      million (ppm) of dietary aflatoxin B1 and inoculated with 10(5) sporulated
      oocysts of E. uzura gained significantly less weight than chicks receiving either
      aflatoxin or coccidia alone. Increased morbidity, mortality and decreased
      efficiency of feed utilization were also evident. The combination of E. uzura
      infection and aflatoxicosis resulted in reduction in packed cell volume (PCV) and
      haemoglobin (Hb). The combination of E. uzura infection and aflatoxicosis in
      Japanese quail may influence the course of coccidial infection due to the
      additive effects of aflatoxin.

PMID- 7732642
TI  - In vitro assessment of two species of nematophagous fungi (Arthrobotrys
      oligospora and Arthrobotrys flagrans) to control the development of infective
      cyathostome larvae from naturally infected horses.
AB  - The ability of two species of nematophagous fungi, Arthrobotrys oligospora and
      Arthrobotrys flagrans (syn. Trichothecium flagrans, Duddingtonia flagrans), to
      control the development of infective larvae in feces from naturally infected
      horses was assessed in vitro. The horses were from a farm where it had been
      previously established that cyathostomes accounted for 100% of the strongyle egg
      output. The feces from these naturally infected horses were mixed with spores of
      each fungal species at four concentrations: 0 (control), 1, 10, and 100 spores
      per egg. Five replicates for each group were incubated for 8 days. Infective
      larvae were harvested using a Baermann technique and counted. The percentage
      reduction in infective cyathostome larvae was calculated for each fungal
      concentration compared to controls. A fungal concentration of 1 spore per egg
      resulted in 40.5% and 32.1% reduction for A. oligospora and A. flagrans,
      respectively. A concentration of 10 spores per egg resulted in 87.4% and 90.5%
      reduction, while 100 spores per egg resulted in 95.8% and 93.9% reduction for A.
      oligospora and A. flagrans, respectively.

PMID- 7732643
TI  - Equine parafilariosis in Iran.
AB  - From March to September 1991, horses (n = 1567), donkeys (n = 112) and mules (n =
      96) were examined for equine parafilariosis by random sampling from different
      areas of Iran. The clinical signs of equine parafilariosis were observed in 136
      cases of two northern areas (1.4% and 41.3% infection rate) and one northeastern
      area (6.3% infection rate). Most of the infected cases were confirmed by
      laboratory findings. All infected cases were followed up to establish the
      epidemiological features. The results suggest that there is one enzootic area in
      Iran, the Caspian coast and Persian Turkman steppes. An annual period of
      appearance of clinical signs coinciding with warm months was observed in all
      infected areas. No clinical sign was observed in cases less than 2 or more than
      15 years of age. The highest infection rates (41.1-73.3%) were observed in
      equidae 4-9 years of age. The enzootic area encompasses the Caspian littoral,
      steppes and forest steppes and has an altitude of up to 1500 m. It has a
      temperature-wet climate. The treatment of 15 infected cases with ivermectin
      subcutaneously at 0.2 mg kg-1, was 100% effective with only one injection.

PMID- 7732644
TI  - Comparison of the effects of basic and neutral zinc salts on chicks infected with
      Ascaridia galli.
AB  - The present study was undertaken to investigate if the use of basic salts of zinc
      in the treatment of ascaridiosis in chicks may present advantages over the use of
      neutral zinc salts. To evaluate this, an infection of Ascaridia galli was induced
      in young male Hisex chicks of 14 and 30 days of age. The performance of the
      infected chicks was improved to a greater extent with the basic salt in doses of
      30 mg Zn2+ kg-1 body weight. Parasite burden, body weight gain and liver zinc
      level were used to assess this performance.

PMID- 7732645
TI  - A comparison of inflammatory exudates released from myiasis wounds on sheep bred
      for resistance or susceptibility to Lucilia cuprina.
AB  - Sheep bred for resistance (R) or susceptibility (S) to fleece rot and myiasis
      (blowfly strike) were experimentally infected with L. cuprina larvae. Exudates
      released from the wound site were collected during the infection at 6, 12, 18 and
      24 h. The exudates were separated using two-dimensional gel electrophoresis, and
      proteins were silver stained and identified by immunoblotting with specific
      antibody and by their isoelectric points and molecular weights. Comparisons of
      exudate composition were made over time and between R and S sheep. Between 6 and
      12 h post larval implantation the exudate was rich in IgG and fibrinogen, which
      is before extensive tissue damage and suggests that the exudate is not simply
      tissue haemorrhage but the result of an inflammatory response by the sheep to L.
      cuprina. The exudate grew in complexity between 12 and 18 h and contained a
      maximum of 74 distinct peptide spots by 24 h. Exudate from wounds on resistant
      sheep contained many more peptides in the first 12 h of infection, suggesting a
      more rapid inflammatory response. The source of proteins from the exudate remains
      speculative; it appears to be composed of many acute-phase proteins, large
      amounts of immunoglobulin G and proportionally low levels of serum albumin.
      Exudate composition is likely to be influenced by the local synthesis of acute
      phase proteins and perhaps immunoglobulins, selective transport to the infection
      site and also enzymic degradation by L. cuprina larval enzymes. The more rapid
      exudation of acute-phase and serum proteins at infection sites on R sheep may
      allow the inhibition of the establishment of fleece rot bacteria or L. cuprina
      larvae under natural challenge.

PMID- 7732646
TI  - Relationships and influences between Boophilus microplus characteristics in tick
      naive or repeatedly infested cattle.
AB  - Six tick-naive male Hereford calves were infested once a month for 6 months with
      18,000 Boophilus microplus larvae on the back and with 400 larvae in a cloth bag
      glued on the lumbar region. Working with the bag ticks, 12 tick characteristics
      were recorded for each infestation. Each tick attribute was analyzed for
      significant differences with those of the first infestation (analysis of
      variance), and for similarity (clustering), degree of relationship (correlation),
      and concomitant variation (regression) against all the other attributes during
      the first, third, and sixth infestations. Some attributes were affected maximally
      by host immunity about the third infestation but recovered later (length of
      feeding, detachment weight, egg weight, start of oviposition, fertility
      efficiency index), whereas others continued to be affected until the last
      infestation (length of oviposition, corpse weight, start of hatching, feeding
      efficiency index). All analyses showed that weight at detachment and egg weight
      were closely related, and corpse weight was partially related to these two. All
      other natural characteristics were largely independent. Length of feeding showed
      no significant relation with weight at detachment nor length of oviposition with
      egg weight. These findings suggest that different tick functions are
      independently affected by host immunity and recommends against estimating general
      anti-tick resistance by the evaluation of only a few tick characteristics.

PMID- 7732647
TI  - Immune responses in sheep after immunization with Toxoplasma gondii antigens
      incorporated into iscoms.
AB  - An immunization and infection experiment using 12 sheep was conducted to study
      the immune responses elicited by an experimental vaccine consisting of Toxoplasma
      gondii antigens incorporated into immunostimulating complexes (iscoms). Five
      sheep were immunized subcutaneously with Toxoplasma iscoms. Two doses were given,
      with a 6 week interval, and 22 days after the second immunization, these five
      sheep and five non-immunized sheep were inoculated orally with T. gondii oocysts.
      The two remaining animals served as non-immunized, uninfected controls. The
      antibody response was analysed by an indirect fluorescent antibody test detecting
      IgM and an enzyme-linked immunosorbent assay detecting IgG. The first
      immunization induced low levels of both IgM and IgG, and the second resulted in
      high levels of IgG but no marked IgM response. After infection, a further
      increase in IgG was observed in the immunized animals. In the non-immunized
      sheep, substantial IgM and IgG levels were detected following infection.
      Immunoblotting analysis indicated that the antibody response to immunization was
      directed against the same T. gondii antigen as the early antibody response after
      infection in the non-immunized sheep. Antibodies recognizing the P30 antigen
      appeared first, followed by antibodies to P22 and other antigens which were
      probably also of membrane origin. Lymphocyte stimulation tests were performed 15
      and 21 days after the last immunization and 105 days after infection. Significant
      antigen-induced proliferative responses were observed after immunization as well
      as after infection.

PMID- 7732648
TI  - Preliminary investigations into the aetiology and treatment of cockle, a sheep
      pelt defect.
AB  - A defect of sheep pelts known as cockle, detectable after depilation, but usually
      first noted only in the pickled pelt or tanned stage of processing, was studied
      to establish causal factor(s) and effective treatments. In addition, data on the
      histology and seasonal prevalence of the disease were obtained. Samples collected
      soon after slaughter from pelts identified at the pickled pelt stage as having
      cockle, had a superficial dermatitis with infiltration of eosinophils. This may
      represent an immediate hypersensitivity reaction of the sheep to lice. Treatments
      of sheep with either insecticides, disinfectants or shearing showed that where
      biting lice (Bovicola ovis) were removed, cockle lesions had either disappeared
      or regressed on pickled pelts. In Trial 1 diazinon reduced cockle prevalence and
      severity substantially; cypermethrin had a less pronounced effect. In Trial 2
      diazinon, cypermethrin, Hibitane and Savlon were equally effective in reducing
      biting louse numbers as shown by counts of lice at 35 and 63 days post-treatment.
      Reduction of cockle on pelts from sheep slaughtered at 39 days post-treatment was
      achieved best by both diazinon and shearing. Examination of other pelts at 67
      days post-treatment showed diazinon and Hibitane to be equally effective in
      reducing cockle. Furthermore, shearing in the absence of insecticides reduced the
      severity and extent of lesions on cockled pelts. The diazinon excipient and zinc
      sulphate were consistently poor at removing lice and reducing cockle prevalence
      and severity. The results have important implications for the leather industry in
      that shearing and good dipping practice with appropriate chemicals at the right
      time can lead to improved pelt quality. However, an incentive scheme for farmers,
      and a means of identifying individual pelts to the farms or origin, are both
      necessary before a marked improvement is likely to occur.

PMID- 7732649
TI  - Activity of praziquantel (0.5 mg kg-1) against Anoplocephala perfoliata (Cestoda)
      in equids.
AB  - Praziquantel injectable formulation was administered at 0.5 mg k-1 per os to 24
      equids naturally infected with 1-183 (average 40) Anoplocephala perfoliata. Drug
      activity was evaluated by a modified critical test method with necropsy 24 h
      after treatment. There was variable efficacy of 0-100% (aggregate average 85%);
      for 18 equids, 93-100%, for three equids, 70-85%, and for three equids, 0-20%.

PMID- 7732650
TI  - Comparative sensitivity of antigen-detection enzyme immunosorbent assay and the
      microhaematocrit centrifugation technique in the diagnosis of Trypanosoma brucei
      infections in cattle.
AB  - Four Boran cattle were infected with Trypanosoma brucei using Glossina morsitans
      centralis and were left untreated throughout the experimental period of 18
      months. During this period, sequential blood samples were collected and examined
      for the presence of antitrypanosome antibodies and their antigens. Using the
      buffy coat technique (BCT), trypanosomes were detected in 38 (16.3%) of the 233
      blood samples. Unlike the BCT, antigen-detection enzyme-linked immunosorbent
      assay (Ag-ELISA) diagnosed infections in 189 (81.1%) of the blood samples. These
      results were supported by the presence of antitrypanosome antibodies in the same
      samples. Thus Ag-ELISA was 5.5 times more sensitive than the BCT. Towards the end
      of the observation period, G.m. centralis tsetse were fed on the aparasitaemic
      cattle to determine whether they still harboured the infection as the persistent
      antigenaemia seemed to suggest. Bloodmeals from the four cattle were infective to
      tsetse, thus emphasising the importance of Ag-ELISA in diagnosis of sub-patent
      infections.

PMID- 7732651
TI  - Somatic antigens of adult Dicrocoelium dendriticum recognised by bile antibodies
      of naturally infected cattle.
AB  - Bile samples, from slaughtered cattle harbouring between 120 and 280 adult lancet
      flukes, were used to investigate the range of somatic proteins inducing local
      antibody responses in naturally infected animals. Lancet fluke infections induced
      local (bile) antibody responses against Tris-buffered saline (TBS) soluble,
      sodium dodecyl sulphate (SDS) soluble and 2-mercaptoethanol (2-Me) soluble
      somatic proteins of adult Dicrocoelium dendriticum. IgA antibody isotypes
      predominated in the response against buffer-soluble somatic antigens, whereas SDS
      soluble and 2-Me-soluble proteins induced similar level of both IgA and IgG1
      antibodies. Analysis of the antigens recognised by particular isotype-specific
      bile antibodies suggests that different antigens preferentially induce isotype
      restricted antibody responses. The bile antibody response was highly species
      specific, only one antigen from somatic protein extracts of Fasciola hepatica
      being precipitated by bile samples showing the highest reactivity against D.
      dendriticum.

PMID- 7732652
TI  - A model for the control of Echinococcus multilocularis in France.
AB  - In some areas of France the prevalence of Echinococcus multilocularis in foxes is
      as high as 50%, whereas less than one in a thousand voles (principally Microtus
      arvalis) are infected. In these regions the control of rabies in foxes is
      achieved by using helicopters to spread bait containing oral vaccine in capsules.
      A mathematical model has been constructed in an attempt to determine if the
      addition of praziquantel to bait would be effective in eradicating E.
      multilocularis, or at least achieve a useful measure of control. It has been
      shown that the qualitative population dynamics of E. multilocularis are not
      affected by the detail of its epidemiology in the intermediate host population.
      The model is, however, sensitive to assumptions about the distribution and
      longevity of the adult worm in the definitive host. Given these assumptions, a
      method is provided that determines the feasibility of eradication conditional on
      the pre-control prevalence in foxes, or predicts the post-control prevalence if
      eradication is not feasible. If experiments could be designed to provide better
      information about the biological factors that determine the epidemiology of this
      parasite in the definitive host, a more reliable assessment of the feasibility of
      control would be achieved.

PMID- 7732653
TI  - An observational study of Eimeria species in housed cattle on Dutch dairy farms.
AB  - The prevalence of oocysts of Eimeria species in calves (n = 334), yearlings (n =
      254) and cows (n = 1314) was determined on 38 Dutch dairy farms. Twelve species
      of Eimeria were identified in faecal specimens by sucrose-flotation. The
      prevalences of Eimeria spp. differed markedly in the different age classes on
      individual farms as well as between farms. The overall prevalence of Eimeria
      oocysts in faecal specimens was 46% for calves, 43% for yearlings and 16% for
      cows. The number of oocysts excreted was generally low in cows and yearlings,
      whereas high numbers of oocysts per gram of faeces (OPG) were exclusively
      observed in calves. No cases of clinical coccidiosis were observed in this
      survey. Linear regression analysis showed that there is significant reduction in
      the OPG levels (P < 0.05) in calves infected with Eimeria, aged between 7 and 38
      weeks. Finally, the data are discussed in relation to management practices and
      the acquisition of immunity.

PMID- 7732654
TI  - A comparison of early and mid grazing season suppressive anthelmintic treatments
      for first year grazing calves and their effects on natural and experimental
      infection during the second year.
AB  - A comparison was made of the efficacy and parasitological sequelae over 2 years,
      of continuous and intermittent periods of anthelmintic suppression applied both
      early and in the middle of the first grazing season of calves. Five groups of 15
      calves grazing separate paddocks within the same field were allotted to one of
      the following treatment regimes during their first year at grass: Group 1,
      untreated controls; Group 2, treated with ivermectin injections at 3, 8 and 13
      weeks after turnout; Group 3, treated with ivermectin injections at 10, 15 and 20
      weeks after turnout; Group 4, treated with a morantel slow release intraruminal
      bolus at turnout; Group 5, treated with a morantel slow release bolus at 10 weeks
      after turnout. Five animals from each group were slaughtered at the end of both
      grazing seasons. Two months after the end of the second season the remaining five
      calves were challenged with an experimental infection of 250,000 third-stage
      larvae (L3) of both Ostertagia ostertagi and Cooperia oncophora. All treatment
      regimes protected the respective calves from parasitic gastroenteritis. Over the
      2 year observation period Groups 2 and 4 showed significantly better weight gain
      than other groups, and at the end of the first season, they were found to harbour
      significantly fewer O. ostertagi in the early fourth stage of development. During
      Year 1, Groups 2 and 3 excreted much lower percentages of Ostertagia spp. eggs
      than other groups. In Year 2, Group 2 excreted a higher percentage of Ostertagia
      spp. eggs although the total egg output was approximately half that of Group 1
      during the same period. The results showed that the effects of anthelmintic
      suppression on egg output of different nematode species was affected by the
      activity of the anthelmintic used.

PMID- 7732655
TI  - Weight gain and the course of some estimators of gastrointestinal nematode
      infection in calves during winter housing in relation to the level of exposure
      during the previous grazing season.
AB  - In two experiments groups of calves were exposed to different levels and patterns
      of infection with Ostertagia spp. and Cooperia spp. The experimental design
      simulated the stereotypic pattern of herbage infestation, including a normal or a
      delayed midsummer increase, under conditions of set-stocking. After this
      simulated 'first grazing season', calves were monitored throughout the subsequent
      winter housing period. No continuing negative effects of previous infection on
      growth performance were observed. Calves in all groups gained on average over 0.7
      kg day-1, irrespective of previous level of exposure. Differences between the
      experiments with respect to either level or pattern of infection during the
      preceding 'first grazing season' were all, to a greater or lesser extent,
      reflected in faecal egg counts, pepsinogen values, gastrin values and antibody
      titres against Cooperia spp. or Ostertagia spp. Depending on the time of
      sampling, pepsinogen values and antibody titres against Ostertagia spp.
      particularly were useful variables for assessing differences in levels of
      infection to which groups of calves had been exposed.

PMID- 7732656
TI  - Japanese encephalitis virus nonstructural protein NS3 has RNA binding and ATPase
      activities.
AB  - Sequence data suggest that Japanese encephalitis virus (JEV) protein NS3 is a
      multifunctional protein with sequence motifs characteristic of a protease and a
      helicase. To examine the functions of JEV-NS3, a fusion protein of NS3 in
      Escherichia coli was generated. Analysis by Western blot using monospecific
      rabbit antisera generated against the fusion protein (anti-MBJEN3) showed that
      NS3 was localized in the membrane fraction of JEV-infected cells and the
      particulate fraction of bacteria extracts. The addition of anti-MBJEN3 sera
      reduced JEV-specific RNA synthesis activity in a in vitro system. In addition,
      NS3 was shown to exhibit RNA binding and ATPase activities, suggesting this
      protein has an important role in viral RNA replication in virus-infected cells.

PMID- 7732657
TI  - Gene-targeted inhibition of transactivation of human immunodeficiency virus type
      1 (HIV-1)-LTR by antisense oligonucleotides.
AB  - We have used an in vitro approach to study the efficiency of antisense
      oligonucleotides in inhibiting LTR-(HIV-1)-directed CAT expression catalyzed by
      tat protein, the functional protein of the transactivator gene. We selected the
      target sequence localized near the 5' end of the tat mRNA. The following
      conclusions can be drawn from the data presented here: a) Antisense
      oligonucleotides modified by conjugation of cholesterol at the 3' end have a
      severalfold higher inhibitory response, b) inhibitory response is dependent on
      the mode of introducing oligonucleotides, and c) the inhibition by antisense
      oligonucleotides is sequence specific and directed towards the targeted region.
      This approach could be useful for targeting functional regions of regulatory gene
      products and designing gene-targeted inhibitors of virus replication.

PMID- 7732658
TI  - Sequence and genomic organization of a rabbit hemorrhagic disease virus isolated
      from a wild rabbit.
AB  - Rabbit hemorrhagic disease virus (RHDV) is a member of the caliciviridae family.
      The nucleotidic sequence of a full-length cDNA of one RHDV isolate (RHDV-SD) is
      reported. The genome is 7437 bases long and includes two ORFs, ORF1 (7034 b) and
      ORF2 (353 b), coding for the polyprotein and the Vp12, respectively. The coding
      sequence for the second structural protein (the capsid protein, Vp60) is located
      at the 3' end of ORF1. Comparison of RHDV-SD with the German RHDV isolated
      revealed 470 nucleotide substitutions (96% homology). The deduced amino acid
      sequences of the two isolates are closely related (98% identity), and no
      hypervariable region could be identified either in the structural or
      nonstructural proteins.

PMID- 7732660
TI  - Cleavage of transcripts of foot and mouth disease virus (FMDV), Asia1 serotype,
      by ribozymes targeted to the VP3 and VP4 genes.
AB  - Two ribozyme genes were designed to cut within the VP4 and VP3 sequences of foot
      and mouth disease virus (FMDV) Asia1 serotype genome. The two genes were
      synthesized and cloned into pBluescript under the control of the T3 promoter. The
      ribozyme designed to cut the VP4 gene contained two catalytic sequences targeted
      to two GUC triplets that are 16 bases apart. The second ribozyme, intended to cut
      VP3, contained one catalytic sequence. Ribozymes obtained from run-off
      transcription from both plasmids were able to cleave viral RNA derived from
      runoff transcripts of plasmids carrying the proper FMDV cDNA inserts. The
      significance of these findings is discussed.

PMID- 7732659
TI  - An analysis of the role of skin Langerhans cells (LC) in the cytoplasmic
      processing of HIV-1 peptides after "peplotion" transepidermal transfer and HLA
      class I presentation to CD8+ CTLs--an approach to immunization of humans.
AB  - Skin Langerhans cells (LC) are antigen-presenting cells capable of expressing MHC
      class I and class II molecules on the plasma membrane. This molecular activity
      was reviewed to combine the knowledge of peptide presentation by MHC and HLA
      class I and class II molecules to prime CD8+ cytotoxic T cells (CTLs) and CD4+ T
      helper cells, respectively. The possible utilization of the skin dendritic cells
      for the development of antiviral CTLs and antibodies by synthetic peptides
      modeled according to the motifs of peptides that naturally interact with the
      peptide binding grooves of the various HLA haplotypes is discussed and evaluated.
      It may be possible that the introduction of synthetic viral peptides with motifs
      to fit the HLA class I haplotypes of a human population to the skin dendritic
      cells will prime selectively the cellular or the humoral immune responses. This
      approach may provide a new vaccination technique that applies synthetic virus
      peptides as vaccines for the immunization of humans. The neuropeptide CGRP
      interacts with LC and modulates antigen presentation.

PMID- 7732661
TI  - Augmentation of c-fos and c-jun expression in transgenic mice carrying the human
      T-cell leukemia virus type-I tax gene.
AB  - To analyze the effect of human T-cell leukemia virus type I (HTLV-I) on cellular
      gene expression and its relation to tumorigenesis, two lines of transgenic mice
      carrying the long terminal repeat (LTR)-env-pX-LTR regions of the HTLV-I genome
      were produced. The transgene was expressed in many organs, including the brain,
      salivary gland, spleen, thymus, skin, muscle, and mammary gland. We found that
      the expression of the c-fos and c-jun genes, but not of the lyn and c-myc genes,
      was augmented 2- to 20-fold in histologically normal skin and muscle of these
      mice. The augmentation was tissue specific, suggesting the involvement of a
      cellular factor in the transgene action. In these mice, a three to seven times
      higher incidence of tumors was seen as compared with the control mice. These
      tumors included mesenchymal tumors, such as fibrosarcoma, neurofibroma, and
      lipoma, and adenocarcinomas of the mammary gland, salivary gland, and lung. The c
      fos and c-jun genes were also activated in these tumors. The possible roles of
      elevated c-fos and c-jun gene expression in tumorigensis are discussed.

PMID- 7732662
TI  - Predicted structure of the adenovirus DNA binding protein.
AB  - The DNA sequence of a portion of the MAV1 SmaI-D fragment coding for the C
      terminal 147 amino acids of the adenoviral DNA-binding protein (DBP) has been
      determined. A multiple sequence alignment was constructed of the MAV1 fragment
      and the DBPs of Ad.2, 4, 5, 7, 12, 40, and 41 to examine the degree of
      conservation of features that have been mapped on the Ad.2 DBP and to identify
      further conserved features. The less conserved N-terminal segment of the protein
      contains two nuclear localization signals and two acidic regions, the host range
      region, and all of the 11 phosphorylation sites. The highly conserved C-terminal
      segment contains a potential leucine zipper and zinc finger motifs. These
      sequence features were mapped onto a predicted secondary structure of the Ad.2
      DBP.

PMID- 7732663
TI  - Complete sequence of the RNA genome of human rhinovirus 16, a clinically useful
      common cold virus belonging to the ICAM-1 receptor group.
AB  - We report here the complete nucleotide sequence and predicted polyprotein
      sequence of HeLa cell-adapted human rhinovirus 16 (HRV16). This virus is more
      suitable than human rhinovirus 14 (HRV14) for clinical studies, and its growth
      and physical properties are favorable for biochemical and crystallographic
      analysis. The complete message-sense RNA genome of HRV16 is composed of 7124
      bases, not including the poly(A) tail. An open reading frame, extending from base
      626 to 7084 predicts a polyprotein containing 2152 amino acid residues.
      Comparison with other rhinovirus sequences shows HRV16 is much more
      representative of human rhinoviruses than HRV14. No apparent relationship was
      found between receptor group and amino acid sequence in VP1, the capsid protein
      bearing the binding site for the intercellular adhesion molecule-1 (ICAM-1) in
      both HRV14 and HRV16.

PMID- 7732665
TI  - Complete nucleotide sequencing of an HPV-1a variant and determination of extant
      errors in the prototype HPV-1a sequence.
AB  - The complete nucleotide sequence of an HPV-1a variant has been determined. The
      variant has over 99% nucleotide identity with the prototype HPV-1a sequence, with
      the majority of mutations occurring in the long control region. Additionally,
      remaining errors in the prototype HPV-1a sequence are reported.

PMID- 7732664
TI  - Capsid protein gene sequence of feline calicivirus isolates 255 and LLK: further
      evidence for capsid protein configuration among feline caliciviruses.
AB  - The capsid protein gene sequences are reported for two feline calicivirus (FCV)
      isolates, one a highly virulent isolate associated with respiratory disease,
      designated 255, and an isolate associated with neuromuscular disorders,
      designated LLK. Both capsid protein sequences conform to a previously described
      hypothesis wherein FCV capsid proteins may be divided into six regions based on
      sequence similarity among isolates. Region A corresponds to the amino-terminal
      area of the protein that is theoretically cleaved to produce the functional
      species. With a large area of sequence identity among isolates, region B contains
      a potential myristilated glycine and a putative ATP/GTP binding site. Region C is
      a short hypervariable sequence of unknown function followed by another conserved
      area designated region D. The E region is an area of extensive amino acid
      sequence hypervariability that presumably contains the antigenic determinants of
      the capsid protein. Region F contains the highly conserved carboxy-terminal
      portion of the protein.

PMID- 7732666
TI  - Nucleotide sequence of a hop stunt viroid variant isolated from citrus growing in
      Taiwan.
AB  - The 303 nucleotide sequence of HSVd-citrus(T), a hop stunt viroid (HSVd) variant
      present in Etrog citron growing in Taiwan, was determined from cDNAs amplified by
      the polymerase chain reaction. HSVd-citrus(T) is very similar to several HSVd
      isolates previously recovered from citrus or cucumber, and exhibits microsequence
      heterogeneity at positions 154 and 181. Phylogenetic analysis using maximum
      parsimony grouped HSVd-citrus(T) with seven other isolates from citrus and
      cucumber in a large cluster of "citrus-type" isolates. A similar analysis
      revealed marked differences in both the extent and distribution of sequence
      variation among naturally occurring isolates of potato spindle tuber viroid.

PMID- 7732667
TI  - [Effect of long-term administration of undevit and its combination with
      cordiamine on hydroxylation, glucuronidation and glutathione conjugation systems
      and lipid peroxidation in rat liver].
AB  - Increase of N-demethylase and antioxidant activities and decrease of amount of
      hydroperoxides were observed in liver of rats after intragastric administration
      of Undevit (1/8 dragee/rats/day, 5 times a week during 2 months). Combination of
      Undevit with Cordiamin (5 mg/rat/day) resulted in augmentation of cytochromes P
      450 and b5 content and activities of their reductases, velocity of amidopyrine
      and ethylmorphine N-demethylation and oxidation of HADPH. Activities of UDP
      glucuronyltransferase, glutathionetransferase and hydrophobity of microsomal
      membranes were also increased. Antioxidant activity was increased and amount of
      hydroperoxides in liver microsomes and homogenates and in plasma was decreased in
      greater degree after administration of combination two compounds than after
      administration of Undevit alone.

PMID- 7732668
TI  - [Effect of pectin additives from cotton on the physical development, nutrition
      and erythrocytes in infants].
AB  - The authors examined 156 babies on bottle feeding or breast and bottle feeding
      against control group of 60 babies whose diets were identical with the study
      group except additional intake of cotton-boll pectin. The latter was used for the
      first time as a biologically active ingredient of infant food (1 g per 100 ml of
      infant milk or food 3 times a day for 45-60 days). As a result of the pectin
      addition the infants of the study group had better nutritional status and
      physical development, their erythrocytic system was superior to that of the
      controls. It is stated that the addition of cotton-boll pectin to baby diet is
      beneficial for their health.

PMID- 7732669
TI  - [Rehabilitation of children with high sickness rate].

PMID- 7732670
TI  - [Trans-uranium elements in food products (review)].
AB  - The data of Russian and foreign authors concerning of level environmental
      contamination and migration of transuranic elements in food chains, metabolism
      and biological danger of nuclides entering in human body with foods are reviewed.
      A level of radionuclide load of population and doses of radiation are discussed
      and the danger is estimated. The doses of radiation from radionuclide ingestion
      are lower than level of allowed radiation safety standards.

PMID- 7732671
TI  - [Ecologic and hygienic evaluation of environment and food products in the areas
      of aluminum plants].
AB  - Content of inorganic fluorides and benz(a)pyrene were studied in soil and plants
      and mineral composition of soil around two aluminium factories. It was shown
      significant contamination of environment around these factories inorganic
      fluorides and benz(a)pyrene, and authors concluded that it is no purpose to
      cultivate agricultural produce at radius as far as 10 km far from these aluminum
      factories.

PMID- 7732672
TI  - [Effect of nitrates on the dynamics of methemoglobin formation in rats of various
      ages].
AB  - Wistar male rats with body mass of 50-83 g and 327-365 g were treated per os with
      solution of sodium nitrate in single dose of 500 or 1000 mg/kg of body mass (on
      the base of nitrate-ion). The level of methemoglobin (MH) and activity of
      methemoglobinreductase (MHR) in blood were analyzed. It was shown that level of
      MH in blood of young immature rats was increased with appearance of two peaks
      after ingestion both doses of nitrate. The appearance of two peaks of MH in
      mature rats was observed only after the high dose of nitrate. Low dose of nitrate
      caused increase of MH concentration only one time. Both doses of nitrate did not
      effect on MHR activity in rat blood.

PMID- 7732673
TI  - [Changes of anaphylactic sensitivity to some food proteins and aflatoxin B1 in
      guinea pigs].
AB  - The study was made of aflatoxin B1 effect on guinea pig alimentary anaphylaxis to
      chicken ovalbumin (CO) and pasteurized cow milk (PCM), of CO-specific IgG
      antibody levels, some serum indices, sensitivity of the animals to LD50
      histamine. In response to aflatoxin B1 alimentary anaphylaxis both to CO and PCM
      became more severe, lethality of the anaphylaxis to CO being in logarithmic
      relation to aflatoxin B1 dose (p < 0.05); specific IgG-antibodies to CO grew in
      number; serum total protein increased against unchanged levels of albumins; the
      activity of gamma-glutamyltransferase inhibited; histamine shock gained severity,
      its lethality being logarithmically related to the aflatoxin B1 dose. The
      discussion covers mechanisms underlying the animal allergic reactivity responses
      to aflatoxin B1.

PMID- 7732674
TI  - [Hygienic aspects of Atlantic fish products utilization in the production of
      infant food].
AB  - The data on toxic element and parasitic contamination of the fish from the
      Atlantic Ocean have been systematized. Basing on the criteria of safety involving
      MAC for heavy metals, pesticides, histamine, radionuclides, absence of parasitic
      contamination, recommendations have been formulated on the conditions under which
      raw fish is ecologically permissible for production of canned food for children.

PMID- 7732675
TI  - [Effect of atherosclerotic diet containing polyunsaturated omega-3 fatty acids on
      level of natural antibodies to prostaglandin F2alpha in patients with ischemic
      heart disease, hyperlipidemia and hypertension].
AB  - The hypolipidemic, antiatherogenic and thrombolytic effects and decrease of
      prostaglandin F2 alpha (PG) excretion were observed in 55 patients suffering from
      Ischemic heart disease, hyperlipidemia and hypertension fed the
      antiatherosclerotic diet containing 20 g of eiconol during 55 days. The low
      initial level of natural antibodies to PGF2 alpha was increased significantly in
      blood serum. Authors consider that decrease of PGF2 alpha level under diet
      influence is connected not only with the change of fatty acid composition of cell
      membranes but also with increasing of natural antibody production.

PMID- 7732676
TI  - [Dairy industry in 21 century].

PMID- 7732677
TI  - [Effect of corn gluten additives into the flour products in patient with non
      insulin-dependent diabetes].

PMID- 7732678
TI  - [Effect of aflatoxin B1 on monooxygenase activity in liver microsomes exposed to
      cytochrome P-450].
AB  - Effect of aflatoxin B1 (AFB1) on microsomal ethoxycumarindeethylase (ECDE) and
      amidopyrindemethylase (APDM) activities in liver of Wistar rats treated with
      inductors of different forms of cytochrome P-450 (P-450) 3-methylcholanthrene (3
      MC) and phenobarbital (PB) were studied. AFB1 caused strong inhibition of ECDE
      activity, induced by 3-MC. 150 for AFB1 was equal 3.2 10-5. In the same time AFB1
      did not effect on basal and PB induced ECDE and APDM activities. Participation of
      MC induced forms of cytochrome P-450 (P-448) in activation of AFB1 is supposed.

PMID- 7732679
TI  - [Comparative biochemical evaluation of riboflavin body status].
AB  - The correlation's between the parameters used as biochemical criteria of vitamin
      B2 provision were studied in rats fed with riboflavin-enriched diets. Based on
      riboflavin-binding apoprotein, highly specific assays of riboflavin in tissues,
      blood and urine revealed close correlation between levels of the vitamin in
      plasma, red cells, the activity of erythrocytic glutathione reductase, PAD
      effect, B2 diet intake, its content in the liver as well as between any of the
      above parameters in couple. This supports adequacy and interchangeability of the
      parameters studied which makes it possible to use any of them for detecting
      vitamin B2 deficiency and relevant vitamin status of the body.

PMID- 7732680
TI  - The Right to Life.

PMID- 7732681
TI  - The process and consequences of institutionalizing an elder.
AB  - This qualitative study was conducted to examine the decision-making process and
      its immediate consequences for family members who placed an elderly loved one in
      a long-term care facility. To explore issues related to the placement process, in
      depth interviews were conducted with 7 individuals who had recently (6 weeks or
      less) placed an older relative. Content analyses of the interviews were
      conducted, and several common themes related to the decision-making process and
      outcomes emerged. Most of the subjects had provided personal care for their
      elderly relative, so placing their loved one in a nursing home often conflicted
      with their view of themselves as an ideal caregiver. During the process of making
      the decision, although family members were given advice and suggestions by health
      care professionals, this input was viewed as inadequate or even detrimental.
      Ultimately, subjects described making the decision to place an elderly relative
      in a long-term care facility as a singular process involving "I" rather than
      "we." The positive and negative role of friends emerged as an important influence
      during and after the placement process. The informal validation of the decision
      to place by peers was the one interaction that family members identified as
      helpful during this process.

PMID- 7732682
TI  - Correlates of stress in HIV disease.
AB  - A group of 53 men with HIV disease participated in this correlational study of
      the relationships among psychological distress, quality of life, uncertainty,
      coping patterns, stress, and CD4+ T-lymphocyte levels. Meaningful correlations (r
      > .40, p < .01) indicated that higher levels of negative-impact stressful
      experiences were associated with more frequent use of emotion-focused coping;
      both higher levels of negative stress and more frequent use of emotion-focused
      coping were associated with lower quality of life, higher psychological distress,
      and more uncertainty; lower quality of life was associated with higher
      psychological distress and more uncertainty; and lower CD4+ counts were
      associated with higher levels of positive-impact stressful experiences.

PMID- 7732683
TI  - Effect of hospital stay on health locus-of-control beliefs.
AB  - Although some studies suggest that health locus-of-control beliefs are not
      affected by situational factors, others show that health locus of control is
      related to health status, indicating that this psychological construct is not as
      stable as suggested. In this study, the stability of health locus of control
      during a hospital admission for a surgical operation is investigated. Although
      test-retest coefficients suggest stability, mean scores of the powerful others
      health locus-of-control belief show an increase during hospital stay, and a
      decrease afterward toward the original level. Furthermore, this study shows that
      patients with fewer hospital experiences have a greater increase and decrease
      than patients with more hospital experiences. Under certain circumstances, health
      locus-of-control beliefs can be temporarily affected by situational factors.

PMID- 7732684
TI  - Reliability and validity of the Modified Erikson Psychosocial Stage Inventory in
      diverse samples.
AB  - The Modified Erikson Psychosocial Stage Inventory (MEPSI) is a relatively simple
      survey measure designed to assess the strength of psychosocial attributes that
      arise from progression through Erikson's eight stages of development. The purpose
      of this study was to employ secondary analysis to evaluate the internal
      consistency reliability and construct validity of the MEPSI across four diverse
      samples: healthy young adults, hemophilic men, healthy older adults, and older
      adults with chronic obstructive pulmonary disease. Special attention was given to
      the performance of the measure across gender, with exploratory analyses examining
      possible age cohort and health status effects. Internal-consistency estimates for
      the aggregate measure were high, whereas subscale reliability levels varied
      across age groups. Construct validity was supported across samples. Gender,
      cohort, and health effects offered interesting psychometric and theoretical
      insights and direction for further research. Findings indicated that the MEPSI
      might be a useful instrument for operationalizing and testing Eriksonian
      developmental theory in adults.

PMID- 7732685
TI  - Issues in conducting research with vulnerable families.
AB  - This article explores methodological and ethical issues in the conduct of
      research with vulnerable families. Some methodological and ethical issues are
      common to all family research, regardless of the families' vulnerability;
      however, many research issues are more problematic in vulnerable families, and a
      few issues are relatively unique to vulnerable families. Vulnerable families are
      defined as families that are susceptible to harm because of their socioeconomic
      status, their minority status, or other stigmatizing status. Methodological
      issues include definition of family; recruitment and retention of participants;
      reliability and validity of instruments; and racism, classism, and sexism.
      Ethical issues include confidentiality, reporting abuse and neglect, conflict of
      research ethics and personal ethics, identifying problems nobody can fix,
      balancing demands and benefits, and interpretation of data. Examples of
      methodological and ethical issues are drawn from several research studies in
      which the primary author was or is currently involved.

PMID- 7732686
TI  - Adult Self-Perception Profile (ASPP) Spanish translation and reassessment for a
      rural, minority population.
AB  - Research has identified problems with self-concept in abused women, and past
      studies have been conducted, primarily within urban populations. Rural and
      minority women also constitute subgroups of women at risk for abuse. This study
      was conducted to reassess reliability and validity of the Adult Self-Perception
      Profile (ASPP), for investigation of relationships between self-concept and woman
      abuse in rural communities, and to develop and perform initial psychometric
      evaluation of a Spanish-language version of the ASPP as a tool to enable
      investigation of self-concept and abuse for rural Mexican American women. ASPP
      development is projected for database formation of theoretically based
      interventions and outcome measurement for woman abuse.

PMID- 7732687
TI  - Translation and validation issues for a multidimensional elderly self-assessment
      instrument.

PMID- 7732688
TI  - Nursing research and nursing practice--teaching the inseparable duo.
AB  - This series of research courses provides (a) an initial emphasis on learning the
      content at the knowledge and comprehension levels; (b) sequential and continuous
      courses so that research is not seen as isolated, and therefore esoteric,
      knowledge; (c) an application component congruent with the clinical/practice
      needs and interests of students; and (d) low faculty-student ratios, at least
      some of the time. Teaching research so that it becomes a fundamental part of
      nursing practice is a goal that must be met. Reading and critiquing research
      provides an ideal avenue for stimulating and embellishing the critical-thinking
      abilities that are so basic to excellence in practice. The development of nursing
      science and the complexities involved in enhancing patient well-being depend on
      the promotion of nursing research and the clinical application of nursing
      research findings. Knowledge about nursing research must be taught; structuring
      teaching so that nursing research becomes a valued and inherent part of clinical
      practice from the beginning is the challenge for nursing educators.

PMID- 7732689
TI  - Refusal to participate in clinical nursing research.

PMID- 7732690
TI  - The use of recombinant human erythropoietin in lung transplantation.
AB  - Recombinant human erythropoietin (r-HuEPO) was administered in 4 lung transplant
      recipients to treat chronic anemia beyond the immediate postoperative period.
      There were 2 males and 2 females with a mean age of 38 years (range 22-49). None
      of the patients had major infection or rejection problems, and no blood products
      were used. Because of different individual responses duration of therapy was 1 to
      17 weeks (median 5) with a total dosage ranging from 8 to 36 x 10(3) IU (mean 21
      x 10(3)). The median single dose was 58 IU/kg (range 36-100). Hemoglobin levels
      increased significantly from 9.1 +/- 0.2 to 12.7 +/- 0.3 g/dl (mean +/- SE; p <
      0.01). There were no side effects. r-HuEPO is recommended in treatment of chronic
      anemia in lung transplant patients to save blood products and to exclude the
      potential risk of transfusion-transmitted viral infections.

PMID- 7732691
TI  - [Echocardiographic grading of cor pulmonale in chronic lung diseases].
AB  - The extent of right heart strain determines the prognosis of chronic lung
      disease. The value of a simple semiquantitative echocardiographic grading system
      for cor pulmonale was assessed in 69 patients (24 females, 45 males, age 61 +/-
      12 years, ranging from 28-82 years) suffering from chronic lung disease. The
      patients were classified by echocardiography into four groups, Grade 0 consisting
      of those without evidence of right heart strain and three groups showing
      increasing severity of change (Grade I: right ventricular hypertrophy; Grade II:
      I + right ventricular dilation; Grade III: II + Dilation of the inferior vena
      cava). Echocardiographic investigation, at least from the subcostal view, and
      grading was possible in all patients. A correlation was found between the
      echocardiographic grading and the mean pulmonary artery pressure (PAP)-normal
      echo study 15.7 +/- 4.8; grade I 21.1 +/- 5.6; grade II 28.8 +/- 10.2; grade III
      39.4 +/- 9.4 mmHg. In addition, patients with stress-induced pulmonary
      hypertension (PHT) were detected by Doppler echocardiography. 6 of 11 patients
      with latent PHT already showed evidence of cor pulmonale (4 Grade I and 2 Grade
      II). In 42 patients (61%) the systolic PAP was estimated by measuring the
      velocity of the tricuspid insufficiency jet with Doppler, and these data
      correlated closely with the invasive data (p < 0.001; r = 0.81). Doppler
      echocardiography for evaluation of cor pulmonale is feasible even in patients
      with chronic lung disease and limited acoustic windows. Semiquantitative grading
      correlates well with invasive data. Here, this technique is useful as a baseline
      study as well as for the follow-up of patients with chronic lung disease.

PMID- 7732692
TI  - [Computer-assisted evaluation of bicycle ergometry for determining level of
      endurance training in physical fitness].
AB  - Recent studies have provided evidence of the importance of aerobic endurance
      training as an independent factor with regard to reducing morbidity and mortality
      from cardiovascular diseases. Clinical routine shows that test methods and
      training recommendations are often not specific enough for efficient, yet safe
      exercise. Software is presented which allows cycle ergometry to be used according
      to standard criteria in clinical practice, with special attention to the
      requirements for training with health benefit. Technical requirements: 1. Cycle
      ergometer with the possibility of increasing exercise intensity by Watt (W)
      increments; 2. ECG or other device for accurate pulse monitoring; 3. IBM
      compatible PC and printer. Based upon the input of data on birth date, sex,
      height, weight, and heart rate (HR) at rest the programme calculates body surface
      area, the reference value of physical work capacity of matching subjects and the
      expected maximal HR (HRmax,exp) and HRmax,exp x 0.95. After the test, input of HR
      at exhaustion (HRmax), maximum achieved W-increment and time cycled at this
      intensity in seconds provides various parameters of the individual work capacity.
      The maximal work performance W (Wmax) is calculated. This value is used to
      provide further calculations of Wmax.kg-1, VO2max.kg-1 and the maximal work
      performance as a percentage of the normal value (LF%). The software provides an
      individual training plan with incremental extension of training time and a
      prescription for heart rate controlled intensity of endurance training based upon
      medically accepted training principles. The software enables a standard test to
      be used and recommends medically efficient and secure quality and quantity
      guidelines for endurance training.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732693
TI  - [Effects of 4-week ergometry training at an intensity of 30% versus 50% of
      maximum performance in an inpatient setting].
AB  - We investigated the effects of bicycle ergometer training (BET, weekly training
      time: 120 min, consisting of 8 units of 15 min). In a centre for cardiovascular
      rehabilitation two groups of 15 patients with coronary heart disease and/or
      hypertension and/or hyperlipidaemia underwent a four-weeks training period. All
      patients avoided other training exercises, they all had the same physiotherapy
      such a massage and the same diet of 800-1200 kcal/day. Current medication was
      kept constant. The main differences between the groups was the intensity of the
      training regimes: 30% versus 50% of the individual maximal physical working
      capacity (PWC), as determined by symptom-limited bicycle ergometry and controlled
      by an individual training heart rate. The higher intensity of training led to a
      highly significant increase of 16% in PWC (p < 0.001), whereas the group with the
      lower training intensity improved by only 5% (p < 0.05). The main effects on body
      weight (reduction in both groups of about 6%), fat metabolism (significant
      reduction in cholesterol and low density lipoprotein (LDL) levels in both
      groups), heart rate and blood pressure (significant decrease in both groups)
      showed no significant differences between the two groups. In general it can be
      assumed that the main effects of the 4-week indoor rehabilitation on fat
      metabolism and blood pressure are due to the diet and weight loss. The 4-week
      period of endurance training was obviously too short to produce any additional
      effects. The more intensive aerobic training, which was more effective on PWC,
      did not reveal better results on fat metabolism, heart rate or blood
      pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732695
TI  - Microalgae as a source of omega 3 fatty acids.

PMID- 7732694
TI  - [Thrombolytic therapy of acute myocardial infarct in advanced age (based on 2
      case reports)].
AB  - The introduction of thrombolysis has reduced the mortality of acute myocardial
      infarction (MI) by 25%. Large-scale studies have revealed that especially
      patients over 65 benefit from this therapy. Nevertheless, many centers apply an
      age limit for thrombolytic therapy due to the higher risk of stroke or bleeding
      in elderly patients. In 1993 181 patients suffering from acute MI were admitted
      to the intensive care unit of the University Clinic of Internal Medicine, Graz,
      and 54 (29.4%) of them were treated with fibrinolytic drugs. In this paper we
      report on the successful thrombolytic management of acute MI in two male patients
      (87 and 88 years old) who were treated with 100 mg recombinant tissue-type
      plasminogen activator complex. As a sign of successful reperfusion a rapid
      increase in plasma creatinine kinase levels and fast amelioration of the ischemia
      related ECG changes were observed. In the follow-up examination after four months
      the first patients showed only minimal exertional dyspnea and was otherwise well.
      The second patient died one month after MI following a laparotomy for ileus. We
      draw the conclusion that patients of advanced age also benefit from thrombolytic
      treatment of acute myocardial infarction, but the indications and
      contraindications have to be carefully observed.

PMID- 7732696
TI  - The nopal: a plant of manifold qualities.

PMID- 7732697
TI  - The corn tree (Brosimum alicastrum): a food source for the tropics.

PMID- 7732698
TI  - Hawthorn (shan zha) drink and its lowering effect on blood lipid levels in humans
      and rats.

PMID- 7732699
TI  - Nutritional value of the alga Spirulina.

PMID- 7732700
TI  - Purslane in human nutrition and its potential for world agriculture.

PMID- 7732701
TI  - Sweet lupins in human nutrition.

PMID- 7732702
TI  - Barley foods and their influence on cholesterol metabolism.

PMID- 7732703
TI  - [Child health in our world].
AB  - The health of children in poor countries is determined by their nutritional
      status and by the economic conditions of their families and societies.
      Socioeconomic differences are correlated with the infant mortality rate (IMR).
      The decline of the IMR in the industrialized countries mainly occurred before
      1960. Programs for Primary Health Care cannot cope with the deterioration of
      economic problems due to the disadvantaged position of the poor countries in the
      world market. The typical clinical pattern of diseases in childhood in the
      tropics is essentially determined by the nutritional status (e.g. measles). The
      advantages of breastfeeding also relate to the immune response after
      immunization. The HIV-epidemic requires social assistance for the future of the
      AIDS-orphans in the first line. Additional assistance is needed for the
      procurement of medication, otherwise HIV-infected patients are in competition
      with non-HIV-infected patients.

PMID- 7732704
TI  - [Electron spin resonance measurements on dried fruit. Carbohydrate composition
      and ESR signal structure of irradiated fruit].
AB  - While in a previous work the ESR spectroscopic detection of irradiated dried
      fruits was reported, in this paper liquid chromatographic determination of the
      carbohydrate fraction of these fruits is introduced and connected with the ESR
      results. After irradiation of dried fruits three different types of ESR spectra
      are observed. In most cases the dried fruits can be attached to these various
      types by means of their sugar composition. It was also found that the ESR spectra
      observed for sucrose-rich fruits are very similar to that of pure sucrose. The
      structure of the ESR spectra can change with storage. Probably, radical
      rearrangement reactions in the samples are responsible for these changes.

PMID- 7732705
TI  - Small scale frying of potatoes in sunflower oil: thermooxidative alteration of
      the fat content in the fried product.
AB  - Sets of 500 g of potatoes were fried discontinuously 15 times in 31 of sunflower
      oil without addition of unused oil. The fat content of fried potatoes increased
      with the number of fryings. The quality of the extracted oil from the fried
      potatoes was evaluated by a combination of column and high performance size
      exclusion chromatography, and compared with their respective fryer oils. Total
      polar content (mg 100 mg oil-1) increased after 15 fryings from 6.2 +/- 0.35 to
      18.7 +/- 0.81 in the oil in the frier and to 21.2 +/- 0.92 in the fries.
      Triglyceride polymers, triglyceride dimers and oxidized triglycerides (mg 100 mg
      oil-1) increased progressively and significantly with the number of fryings
      either in the fryer oil or in the extracted oil, being the content of
      triglyceride dimers significantly higher in the extracted oil than in the oil in
      the fryer. Potatoes from the 15th frying contained more total alteration-oil
      products, triglyceride polymers, triglyceride dimers and oxidized triglycerides
      (g 100 g fresh matter-1) than potatoes from the 8th frying (all p < 0.01). This
      fact may be of special relevance for some people who usually eat large quantities
      of potatoes fried in oils with a null or low turnover of fresh oil.

PMID- 7732706
TI  - [Effect of rapeseed in beef cattle feeding on fatty acid composition, vitamin E
      content and oxidative stability of body fat].
AB  - Four groups of five fattening bulls each consumed a concentrate--wheat straw-diet
      (2.5:1) supplemented with either 0, 7, 14 or 21% ground rape seed for 350 days.
      Rape seed contained 427 g crude fat (ether extract) and 127 mg vitamin E per kg
      dry matter. The supplementation with rapeseed increased the fat concentrations in
      the rations from 25 to 50, 75 and 100 g, and of vitamin E from 11 to 19, 26 and
      34 mg per kg dry matter. All bulls were slaughtered with about 560 kg body
      weight. Fatty acid composition of depot fat and of the fat of musc. long. dorsi
      were determined by gas liquid chromatography. Vitamin E concentrations in blood,
      depot fat and muscle were determined by HPLC. Oxidative stability of depot fat
      was measured as induction time by means of rancimat-test. Rape seed
      supplementation decreased C16-fatty acids and increased C18-fatty acids in depot
      and muscle fat. Muscle fat contained significantly more mono and poly unsaturated
      fatty acids (40.2 and 7.4%) than depot fat (33.5 and 2.0%, respectively). Rape
      seed supplementation enhanced significantly the vitamin E-concentrations in all
      body samples. In depot fat vit. E increased from 4.5 to 7.3, 8.5 and 14.9
      micrograms/g. Induction time increased from 10.9 to 18.5, 16.1 and 19.5 h, when
      0, 7, 14 or 21% rapeseed were added.

PMID- 7732708
TI  - [Nutrient intake in permanent night shift workers].
AB  - By means of a modified weight record technique, total dietary intake was obtained
      in 24 permanent night-shift workers during a period of 7 consecutive days; intake
      data were attached to eight defined meals. As a control, 25 shift workers of the
      same company were investigated during the morning shift. Mean daily energy intake
      was 2866 +/- 616 kcal (12.0 +/- 2.6 MJ) including 14% protein, 39.5% fat, 37.8%
      carbohydrates, and 8.7% alcohol. Statistically significant differences between
      groups were found for vitamin E and polyunsaturated fatty acids. In both groups
      intake data for vitamin A, D, zinc and dietary fiber did not meet 3/4 of the
      recommendations of the German Nutrition Society. In contrast to controls,
      nutrient intake of the permanent night-shift workers was slightly less during
      weekend days; mean meal frequency decreased from 5.4 (weekday) to 4.3. The
      distribution of total daily nutrient intake to different meals partly did not
      agree with existing recommendations; however, the deviation seems reasonable.
      Regarding the risks for accidents as well as the working capacity, the relatively
      high alcohol intake during working hours has to be criticized.

PMID- 7732707
TI  - [Effect of isoenergetic replacement of starch by olive oil and fish oil
      concentrations of lipids in plasma and lipoprotein fractions in swine].
AB  - Two experiments with sows were performed to investigate the effect of
      isoenergetic replacement of starch by fish oil or olive oil on concentrations of
      lipids in plasma and lipoproteins. The first experiment was based on a cross-over
      design with three periods, each lasting 16 days. Each sow was fed during one of
      the periods a basal ration with isoenergetic addition of (1) starch (495 g/d),
      (2) olive oil (221 g/d), or (3) fish oil (223 g/d) based on energetic requirement
      for maintainance. The second experiment was based on a cross-over design with
      eight periods, each lasting 16 days. In the first and in the last periods, each
      sow was fed the basal ration. In the other six periods, each sow was fed the
      basal ration with addition of two different amounts of (1) starch (284/568 g/d),
      (2) olive oil (140/281 g/d), or (3) fish oil (141/282 g/d). The two different
      amounts of addition were selected to exceed the energetic requirement for
      maintainance by 25% or 50%. In both experiments blood samples were taken before
      each change of the ration. In both experiments olive oil elevated the
      concentration of cholesterol in plasma in comparison with starch. This elevation
      was due to a large elevation in high-density lipoproteins (HDL), and a slight
      elevation in low-density lipoproteins (LDL) and very-low density lipoproteins
      (VLDL). The ratio between HDL and LDL cholesterol was increased by feeding olive
      oil. The effect of olive oil on concentrations of cholesterol in plasma and
      lipoproteins was dose-dependent. In both experiments none of the two dietary oils
      significantly changed concentrations of triglycerides in plasma and lipoproteins.
      Concentrations of phospholipids in plasma, HDL, and LDL were elevated by olive
      oil. In both experiments addition of fish oil elevated concentration of
      cholesterol in plasma due to elevated cholesterol concentration in LDL.
      Concentration of HDL cholesterol was not changed by fish oil. Thus, the ratio
      between HDL cholesterol and LDL cholesterol was lowered by fish oil. The effect
      of fish oil on concentration of cholesterol in plasma and lipoproteins was also
      dose-dependent. Fish oil had no significant effect on phospholipid concentrations
      in plasma and lipoproteins. In conclusion, in the present experiment olive oil
      caused antiatherogenic changes of the lipoprotein profile, whereas fish oil
      caused proatherogenic changes of the lipoprotein profile.

PMID- 7732709
TI  - [Medical historical considerations on the 100th anniversary of the discovery of
      roentgen rays].

PMID- 7732710
TI  - [The significance of insulin resistance and hyperlipidemia in microvascular
      angina (syndrome X)].
AB  - Patients with chest pain and normal epicardial coronary arteries are
      characterized by an impairment of myocardial perfusion reserve. Functional and
      morphological abnormalities of the intramyocardial arterioles are suggested to be
      responsible for this, possibly as a consequence of hypertension and/or left
      ventricular hypertrophy. In an attempt to isolate predisposing factors of
      microvascular angina we investigated 34 patients (15 f, 19 m) with a mean age of
      53 +/- 7 years. They were diagnosed as microvascular angina without hypertension
      or left ventricular hypertrophy. Parameters such as plasma insulin, glucose,
      cholesterol, LDL-cholesterol, triglycerides, (VLDL-cholesterol) and fibrinogen
      were determined for a metabolic profile. Furthermore, insulin and glucose were
      measured after an oral glucose load of 100 g glucose (OGTT) over 3 h. All
      parameters were compared to a control group of 15 healthy people matched for age
      and body mass index. In the study population systolic blood pressure was within
      normal limits at 137 +/- 17 mm Hg and thus higher than control at 124 +/- 11 mm
      Hg (p < 0.02). Furthermore, diastolic blood pressure was 85 +/- 7 mm Hg compared
      to 78 +/- 9 mm Hg in controls (p < 0.02). Insulin was significantly elevated in
      patients with microvascular angina 90 min (median: 101 vs 54 microU/ml; p < 0.01)
      and 120 min (median: 88 vs 51 microU/ml; p < 0.05) after ingestion of 100 g
      glucose. The fasting glucose was elevated at 98 +/- 12 compared to 87 +/- 7 mg/dl
      in controls (p < 0.01). Glucose concentration was also elevated after 30 min at
      176 +/- 28 compared to 148 +/- 32 mg/dl (p < 0.02), after 45 minutes (198 +/- 35
      compared to 152 +/- 53 mg/dl) (p < 0.01) and 60 minutes (193 +/- 44 compared to
      145 +/- 54 mg/dl) (p < 0.01). In microvascular angina parameters such as total
      cholesterol: (244 +/- 46 vs 199 +/- 29 mg/dl (p < 0.01)), LDL-cholesterol (157 +/
      41 vs 122 +/- 18 mg/dl (p < 0.01)) and fibrinogen: (377 +/- 150 vs to 285 +/- 69
      mg/dl (p < 0.03)) were elevated. These findings suggest a pathogenetic role of
      insulin resistance, hyperlipoproteinemia and elevated levels of fibrinogen for
      impaired myocardial coronary reserve. This metabolic constellation as well as
      exhaustion of coronary reserve is often found in hypertensive patients and may
      identify microvascular angina as an early stage of hypertensive heart disease
      before manifest hypertension has developed.

PMID- 7732711
TI  - [Assessment of severity of mitral insufficiency--value of various color Doppler
      echocardiographic methods].
AB  - A total of 79 patients with mitral regurgitation (age 62 +/- 11 years, 45 men, 34
      women) quantified by angiography was studied using color-Doppler imaging of
      isovelocity surface areas in the flow convergence region proximal to the
      regurgitant orifice (PISAs), of the jet cross-section at the level of the
      regurgitant orifice and of the regurgitant jet in the left atrium. The PISA-radii
      for the flow velocities (aliasing borders) of 28 and 41 cm/s, the cross-sectional
      jet area and the jet length, and relation of jet area to left atrial area were
      measured. The sensitivity for the detection of mitral regurgitation was at least
      97% for the color-Doppler methods investigated in these patients in which a
      sufficient imaging was obtained. However, a sufficient imaging of the flow
      convergence region and the jet cross-section was not possible in about 5% of all
      patients. The PISA-radii for both flow velocities and the cross-sectional jet
      area correlated more closely with the angiographic grade (rSp = 0.79-0.80, p <
      0.001) than the jet area (rSp = 0.39, p < 0.001), jet length (rSp = 0.37, p <
      0.001), and relation of jet area to left atrial area (rSp = 0.31, p < 0.01) did.
      A correct differentiation of grades I to II from grades III to IV mitral
      regurgitation was provided in 93-95% of patients by the proximal flow convergence
      and by the cross-sectional jet area method and, at most, in 76% of the patients
      by the jet area method using the uncorrected jet area.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7732712
TI  - [Determinants of arterial embolism with special reference to atheromatous changes
      of the thoracic aorta].
AB  - Potential sources of arterial embolism were evaluated with special emphasis on
      aortic atheromatosis in patients who underwent transesophageal echocardiography
      for various clinical reasons. Among 375 patients, 166 had suffered from
      cerebrovascular disease or peripheral embolism and 209 were free from symptoms of
      embolism. Univariate analysis revealed that atheromatosis of the aortic arch and
      descending aorta as well as cardiac thrombi, aneurysms of the interatrial septum
      and arterial hypertension were significantly more common in patients who had a
      history of embolism or ischemic stroke. In a stepwise multiple regression
      analysis, aortic arch atheromatosis (odds ratio 1.7, 95% CI 1.1-2.6), cardiac
      thrombi (odds ratio 4.1, 95% CI 1.7-9.8), atrial septal aneurysm (odds ratio 3.0,
      95% CI 1.2-7.8) and arterial hypertension (odds ratio 1.8, 95% CI 1.1-3.0) were
      determined as independent predictors of embolic symptoms. We conclude that
      atheromatous lesions of the aortic arch are an independent risk factor for
      arterial embolism and ischemic stroke among other well known sources of embolism.

PMID- 7732713
TI  - [Dissection following balloon angioplasty: predictive possibilities using pre
      interventional intravascular ultrasonography].
AB  - The purpose of this study was to examine the association between qualitative and
      quantitative lesion characteristics before and the incidence of dissection after
      balloon angioplasty as assessed by intravascular ultrasound imaging. Thirty-seven
      patients (5 women, 32 men, aged 60 +/- 9 years) with 41 dilated lesions were
      examined with a 3.5 F, 20 MHz rotational tip intravascular ultrasound imaging
      system before and immediately after coronary balloon angioplasty. Images were
      assessed for plaque composition, topography and postinterventional effects on the
      plaque morphology. Quantitative measurements of lumen area, total arterial area
      and plaque area were performed in the dilated vessel segment. Plaque morphology
      was concentric in 18 lesions (44%) and eccentric in 23 lesions (56%). Fourteen
      lesions (34%) showed no calcification, 15 lesions (37%) were superficially and 12
      lesions (29%) were deeply calcified. Four distinct changes of the plaque
      morphology were manifested by ultrasound imaging after balloon angioplasty.
      Dissection with detachment of the plaque from the underlaying wall was found in
      10 lesions, plaque splitting in 9 lesions, superficial tears in 6 lesions, and
      smooth plaque contours in 16 lesions. The incidence of dissection detected by
      intravascular ultrasound was significantly greater in eccentric lesions (p =
      0.03) and in stenoses with a small total arterial area (p = 0.006). The incidence
      of dissection was significantly increased in vessels in which balloon cross
      sectional area exceeded 50% of the total cross-sectional vessel area as compared
      to those with a smaller balloon-to-vessel ratio. Preinterventional IVUS imaging
      provides information about the target stenosis which can be used to assess the
      risk of postinterventional dissections. In addition to the size of the balloon in
      relation to vessel cross-sectional area, the features small total vessel cross
      sectional area and eccentric stenosis morphology in the preinterventional IVUS
      study predispose to an increased risk of dissection. Further studies have to
      elucidate the influence of dissections on late outcome after angioplasty.

PMID- 7732714
TI  - [Life style changes in patients with myocardial infarct in the framework of
      intramural and ambulatory rehabilitation--results of a German pilot study].
AB  - To assess whether German patients would make comprehensive lifestyle changes as
      designed and successfully tested in the San Francisco Lifestyle Heart Trial, we
      recruited 25 patients who received usual care, and 15 patients who made lifestyle
      changes during a 6-week in-hospital rehabilitation program followed by a 3-month
      ambulatory period. The intervention program consisted of a low-fat vegetarian
      diet, stress management techniques, aerobic exercises, and group support
      meetings. The program was well accepted, and high compliance resulted in
      significant changes in the patients' diet, stress management, and exercise
      activity. For instance, fat intake dropped from 36% to 9% of total calories. As
      patients in both groups received 20 mg/day of Pravastatin, a lipid-lowering drug,
      lipid levels dropped significantly in both groups (30% in the intervention group
      and 27% in the control group). Thus, the combined effect of behavioral and drug
      treatment did not result in a substantial additional lipid-lowering effect.
      Within the intervention group significant improvement in quality of life
      occurred. In conclusion, the lifestyle heart program can be successfully
      implemented in a German rehabilitation setting which combines in-hospital and out
      patient activities. However, participation in the current program is limited to
      highly motivated, well educated coronary patients.

PMID- 7732715
TI  - [10 years of therapy with implantable defibrillators--observation in 353
      patients].
AB  - Since January 1984, the cardioverter-defibrillator (ICD) has been implanted in
      353 patients (pts). Epicardial ICD implantation was performed in 207 pts and 146
      pts underwent non-thoracotomy ICD implant. Overall operative mortality was 3%
      (12/353 pts) and was significantly higher in pts with epicardial ICD implantation
      (11/207 pts, 5%) than in patients who received non-thoracotomy ICDs (1/146 pts, <
      1%) (p < 0.05). During a mean follow-up of 25 +/- 23 months, 63 pts (19%) died: 8
      pts (0.8% per year) from sudden arrhythmic death and 6 pts (0.8% per year)
      suddenly without an underlying arrhythmia. Cardiac death was observed in 36 pts
      (4% per year) and 13 pts (2% per year) died from other causes. Appropriate ICD
      discharges were observed in 245 pts (72%) with a mean incidence of 22 +/- 44 IC
      discharges per pt. In pts with third-generation ICDs, 3,542 ventricular
      tachyarrhythmias (VTA) were observed and terminated by primary ICD shocks in 778
      VTA (22%). Antitachycardia pacing was attempted in 2,764 VTA (78%) and was
      successful in 2,484 VTA (90%).

PMID- 7732716
TI  - [High-frequency current ablation of a Mahaim fiber at the tricuspid annulus].
AB  - The Mahaim syndrome is a rare variant of accessory pathways. Typically, a normal
      surface ECG and paroxysmal tachycardias with left bundle branch block morphology
      are found. The anatomic correlate is an atrioventricular or atriofascicular fiber
      with decremental conduction properties. Criteria for intracardiac mapping of the
      atrial insertion of such a fiber include: 1) maximal preexcitation and a short
      stimulus-QRS interval with differential pacing from the atrial aspect of the
      tricuspid annulus, and 2) recording of an accessory pathway potential ("M"
      potential). We report a case of a patient that underwent successful
      radiofrequency ablation of a Mahaim fiber at the tricuspid annulus.

PMID- 7732717
TI  - [Effects of age in the correction of isthmus stenosis on postoperative stiffness
      of the aorta].
AB  - Operative surgery for coarctation aims to eliminate the narrowed segment of the
      aorta and to restore a normal function of the aortic Windkessel, which depends on
      normal elastic properties of the aorta. To evaluate the effect of age at
      coarctectomy on the postoperative aortic elasticity, parameters of regional wall
      stiffness within the aortic arch were determined in 24 children after
      coarctectomy by means of echocardiography and blood pressure measurements. Actual
      data were compared with reference data (mean value normalized to body weight: mn
      +/- SD) obtained from n = 43 children, adolescents and young adults (age 1 month
      to 28 years; mean 12.6 years): elastic modulus Epn = 0.20 +/- 0.07
      Mdyn/cm2/kg0.11; stiffness index beta = 3.45 +/- 1.3; diameter Dn = 0.52 +/- 0.08
      cm/kg0.37. The results revealed that 4.9 years (mean) after coarctation repair
      within the first year of life (mean 3.2 months, n = 10) the parameters of
      elasticity and the diameter did not differ from normal. In those n = 5 children
      operated on in the age of 4.7 years there was a tendency towards increased aortic
      stiffness and reduced diameter 8.9 years later. In n = 9 children with a mean age
      of 9.2 years at operation the elastic modulus was increased 7.6 years later: Epn
      = 0.28 +/- 0.11 Mdyn/cm2/kg0.11; (p < 0.01). The diameter of the proximal aortic
      arch was significantly reduced (DN =0.42 +/- 0.08 cm/kg0.37., P < 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7732718
TI  - [Therapeutic efficacy and diagnostic potential of adenosine in infants and
      children].
AB  - In an open study a total of 53 episodes of supraventricular reentrant tachycardia
      in 31 infants and children were treated with intravenous adenosine at two
      centers. Adenosine was given as a rapid intravenous bolus injection beginning
      with a dose of 0.1 mg/kg. If there was persistence of the dysrhythmia dosage was
      increased in 0.05 mg/kg-steps up to a maximum dose of 0.3 mg/kg if necessary. The
      median dose required for successful termination of the tachycardias was 0.15
      mg/kg. In 26 patients with 48 episodes of regular narrow-QRS-complex tachycardia
      adenosine was used as the therapeutic agent of first choice. In all patients a
      shortlasting atrioventricular block occurred within seconds after the
      administration of adenosine. In 42 of 48 episodes of tachycardia (87%) the
      dysrhythmias were converted to a stable sinus rhythm. In six episodes (13%)
      recurrence of the tachycardia was observed immediately. In five children
      adenosine was used for diagnostic purpose: in three children with wide-QRS
      complex tachycardia successful termination with adenosine proved the
      supraventricular origin of the dysrhythmia. In two children with suspected atrial
      flutter adenosine-induced atrioventricular block allowed identification of
      flutter waves in one patient while in the other patient no effect of adenosine
      was seen. Side-effects such as flush, chest-pain or abdominal pain were frequent
      but mild and only of a few seconds' duration. No influence of adenosine on blood
      pressure was noted. Only in one child with previously unknown sinus node
      dysfunction was a relevant electrophysiologic side effect seen: a prolonged sinus
      arrest with asystole of 12 seconds' duration occurred after adenosine
      administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732719
TI  - [Letter concerning the paper "Significance of temperature-controlled energy
      release in high-frequency catheter ablation of accessory pathways", Kottkamp et
      al., Z Kardiol 83:577-581 (1994)].

PMID- 7732720
TI  - Perfect state of Rhodomyces dendrorhous (Phaffia rhodozyma).
AB  - After mother-daughter cell conjugation, formation of long holobasidia with
      terminal basidiospores was observed without mycelium production in Rhodomyces
      dendrorhous (including the type strain of Phaffia rhodozyma) on polyol-containing
      media. Basidiospores are not forcibly discharged and germinate by budding. A new
      genus Xanthophyllomyces (Filobasidiaceae, Tremellales) with a species, X.
      dendrorhous, is proposed for the teleomorphic state of R. dendrorhous.

PMID- 7732721
TI  - Characterization of a glycerol/H+ symport in the halotolerant yeast Pichia
      sorbitophila.
AB  - Pichia sorbitophila is a halotolerant yeast capable of surviving to extracellular
      NaCl concentrations up to 4 M in mineral medium when glucose or glycerol are the
      only carbon and energy sources. Evidence is presented here that glycerol, the
      main compatible solute this yeast accumulates so as to maintain osmotic balance,
      is actively co-transported with protons. This transport system was shown to be
      constitutive, not needing induction by either glycerol or salt, and was not
      repressible by glucose. In glucose- or glycerol-grown cells, a simple diffusion
      was detectable, and iterative calculations were performed to calculate kinetic
      parameters, in the presence and in the absence of NaCl. At 25 degrees C, pH 5.0,
      in glucose-grown cells these were: Km = 0.81 +/- 0.11 mM and Vmax = 634.2 +/-
      164.8 mumol h-1 per g (glycerol); Km = 1.28 +/- 0.60 mM and Vmax = 558.6 +/-
      100.6 mumol h-1 per g (protons). Correspondent stoichiometry was approximately 1,
      either for these conditions or in the presence of 1 M-NaCl. An increase in
      accumulation capacity was evident when different concentrations of NaCl were
      present. This capacity was shown to be dependent on delta pH and membrane
      potential, consistently with an electrogenic character. We suggest that the main
      role of this system is in osmoregulation, by keeping glycerol accumulated inside
      the cells, compensating for leakage, due to its liposoluble character.

PMID- 7732722
TI  - Construction of a complete genomic library of Saccharomyces cerevisiae and
      physical mapping of chromosome XI at 3.7 kb resolution.
AB  - A consortium of European laboratories has been organized to systematically
      sequence the genome of Saccharomyces cerevisiae. As part of the BIOTECH program
      aimed at sequencing chromosomes XI and II, we have constructed a total genomic
      library of yeast strain FY1679 (a direct S288C derivative) into cosmid vectors
      pWE15 and pOU61cos. Primary clones from four independent libraries totalling 190
      genome equivalents have been stored at -80 degrees C. A subset of 1939
      independent clones (six genome equivalents) was hybridized using purified
      chromosomes XI and X as probes. A total of 147 chromosome XI-specific cosmid
      clones was used to construct the physical map of that chromosome. Mapping methods
      included a combination of classical bottom-up strategies (fingerprinting,
      hybridizations) and a novel top-down strategy using I-SceI chromosome
      fragmentation. The 147 cosmid clones form a unique contig covering the entire
      chromosome XI (666 kb) with the sole exceptions of the (C1-3A)n repeats of the
      telomeres. Colinearity of cosmid inserts with yeast DNA was directly verified. A
      complete EcoRI map of chromosome XI was deduced from partial overlaps of cosmids
      and used for the sequencing program. Comparison of this map with the genetic map
      shows unexpected divergences that have been solved by subsequent genetic
      analysis, yet underline the necessity of independent physical mapping in genome
      projects.

PMID- 7732723
TI  - Transcriptional regulation of the Saccharomyces cerevisiae HXK1, HXK2 and GLK1
      genes.
AB  - In Saccharomyces cerevisiae, the transcriptional regulation of most glycolytic
      genes has been extensively studied. By contrast, little is known about the
      transcriptional control of the three glucose-phosphorylating enzymes, although
      this catalytic reaction has an important role in the regulation of cell
      metabolism. In this paper, we describe the transcriptional regulation of the
      HXK1, HXK2 and GLK1 genes in the hope of revealing differences in the steady
      state levels of mRNA associated with a particular carbon source used in the
      culture medium. Our results provide evidence supporting a differential expression
      of the three genes depending on the carbon source used for growth. We have also
      studied the induction and repression kinetics of mRNA expression for the HXK1,
      HXK2 and GLK1 genes.

PMID- 7732724
TI  - Development and application of an in vivo system to study yeast ribosomal RNA
      biogenesis and function.
AB  - We have developed a system for mutational analysis of Saccharomyces cerevisiae
      ribosomal RNA in vivo in which yeast cells can be made completely dependent on
      mutant rRNA and ribosomes by a simple switch in carbon source. The system is
      based on a yeast strain defective in RNA polymerase I (Pol I) transcription [Nogi
      et al. (1991) Proc. Natl. Acad. Sci. USA 88, 3962-3966]. This normally inviable
      strain was rescued by integration of multiple copies of the complete 37S pre-rRNA
      operon under control of the inducible, Pol II-transcribed GAL7 promoter into the
      rDNA repeat on chromosome XII. The resulting YJV100 strain can only grow on
      medium containing galactose as the carbon source. A second, episomal vector was
      constructed in which the rDNA unit was placed under control of the constitutive
      PGK1 promoter. YJV100 cells transformed with this vector are now also able to
      grow on glucose-based medium making the cells completely dependent on plasmid
      encoded rRNA. We show that the Pol II-transcribed pre-rRNA is processed and
      assembled similarly to authentic Pol I-synthesised pre-rRNA, making this 'in vivo
      Pol II system' suitable for the detailed analysis of rRNA mutations, even highly
      deleterious ones, affecting ribosome biogenesis or function. A clear
      demonstration of this is our finding that an insertion into variable region V8 in
      17S rRNA, previously judged to be neutral with respect to processing of 17S rRNA,
      its assembly into 40S subunits and the polysomal distribution of these subunits
      [Musters et al. (1989), Mol. Cell. Biol. 9, 551-559], is in fact a lethal
      mutation.

PMID- 7732725
TI  - Characterization of Schizosaccharomyces pombe his1 and his5 cDNAs.
AB  - We have isolated Schizosaccharomyces pombe cDNAs corresponding to the genes his1+
      and his5+. The his1 cDNA was isolated by functional complementation of the His-
      phenotype in a his1-29 gcn3 Saccharomyces cerevisiae strain, while the his5 cDNA
      was isolated as a suppressor of the 3-amino-1,2, 4-triazole (3-AT) sensitivity in
      a gcn3 S. cerevisiae strain. his1 and his5 are each present in single copy in
      haploid S. pombe. As is the case with S. cerevisiae, we have found that the
      growth of wild-type strains of S. pombe is sensitive to 3-AT, an inhibitor of
      imidazoleglycerol-phosphate dehydratase. This enzyme is encoded by the HIS3 gene
      in S. cerevisiae and the his5+ gene in S. pombe. Treatment of S. pombe cells with
      3-AT leads to a small increase in the level of the his5 transcript, but no effect
      is seen on the level of the his1 transcript. This is in contrast to larger
      increases in transcription of amino acid biosynthetic genes, regulated by the
      general amino acid control, seen previously in similarly treated cultures of S.
      cerevisiae. These results suggest that there are likely to be some differences in
      the regulation of amino acid biosynthesis between these two yeasts.

PMID- 7732726
TI  - Recovery of gene function by gene duplication in Saccharomyces cerevisiae.
AB  - A prototroph revertant (Rev9) selected from an ATCase- mutant of the URA2 gene
      containing three nonsense mutations was shown to contain two ATCase coding
      sequences. We cloned both ATCase coding areas to show that the duplicated locus
      (dl9) was the only functional one. Its size corresponded roughly to the second
      half of the URA2 wild-type gene. Sequence analysis of the 5' end of dl9 indicated
      that this duplicated sequence was inserted within the intergenic region close to
      the MRS3 gene and was transcribed from an unknown promoter divergently from the
      MRS3 gene. The event leading to the revertant strain Rev9 included a
      rearrangement that increased the size of chromosome X by about 60 kb. In
      agreement with such a rearrangement, recombination was undetectable in the
      vicinity of the locus dl9. Genetic mapping confirms that the MRS3 gene is 2 cM
      distal to the URA2 gene on the right arm of chromosome X.

PMID- 7732727
TI  - Molecular cloning of the plc1+ gene of Schizosaccharomyces pombe, which encodes a
      putative phosphoinositide-specific phospholipase C.
AB  - Exploiting the polymerase chain reaction, we have isolated a gene that encodes a
      putative phosphoinositide-specific phospholipase C (PLC) of the fission yeast
      Schizosaccharomyces pombe. Inspection of the nucleotide sequence of the gene
      revealed an open reading frame that can encode a polypeptide of 899 amino acid
      residues with a calculated molecular mass of 102 kDa. This putative polypeptide
      contains both the X and Y regions that are conserved among three classes of
      mammalian PLC, and also contains a presumptive Ca(2+)-binding site (an E-F hand
      motif). The structure of the putative protein is most similar to that of the
      delta class of PLC isozymes. To investigate the role of this gene, designated
      plc1+, gene disruption was carried out by interrupting the coding region with the
      ura4+ marker. Growth of plc1 cells was temperature-sensitive in rich medium, and
      cells could not grow in synthetic medium. Expression of the PLC1 gene of
      Saccharomyces cerevisiae suppressed the growth defect phenotype of plc1- cells, a
      strong suggestion that the plc1+ gene encodes PLC.

PMID- 7732728
TI  - Physical map locations of the phospholipid biosynthetic structural and regulatory
      genes of Saccharomyces cerevisiae.
AB  - Here we report the physical map locations of five genes required for phospholipid
      biosynthesis in Saccharomyces cerevisiae. These include four structural genes
      (INO1, CHO2, OPI3 and PIS1) and one global negative regulatory gene (UME6).
      Collectively, this information completes the mapping of all phospholipid
      biosynthetic structural and regulatory genes identified to date.

PMID- 7732729
TI  - Denaturation of fish proteins during frozen storage: role of formaldehyde.
AB  - Proteins of fish muscle undergo chemical and physical changes during frozen
      storage which may result in, under certain conditions (i.e. long periods of
      storage, poor freezing practices, temperature fluctuations, etc), loss of
      quality, reflected mainly by an unacceptable texture as well as an undesirable
      flavour, odour and colour. In frozen gadoid fish species, most of these changes
      are caused by the production of formaldehyde in the muscle. Formaldehyde is
      produced, along with dimethylamine, by the enzymatic reduction of trimethylamine
      oxide (TMAO). Many aspects of formaldehyde production by TMAO demethylase
      (TMAOase) have been studied throughout the last decade. In addition, different
      approaches have been used to investigate the effect of formaldehyde production on
      protein denaturation and the associated muscle textural changes. Some insight
      into the reaction between protein and formaldehyde has clarified the possible
      mechanism of formaldehyde-mediated denaturation. However, evidence of covalent
      bonding between proteins and formaldehyde, to form crosslinks, has not explained
      fully the changes observed in fish proteins during frozen storage. The study of
      cold-induced denaturation of proteins might give new clues for further
      investigation of the problem. The implications of formaldehyde in toxicological
      and nutritional issues is also reviewed, as general concern about the safety of
      food products is a growing field in food science. Finally, different approaches
      have been proposed to avoid the detrimental action of formaldehyde during frozen
      storage of gadoid fish; they are some of the practical applications of the
      knowledge acquired after years of study of different workers in the field.

PMID- 7732730
TI  - Composition of plant cell walls.
AB  - The present study reviews the most recent research published (starting
      approximately in the 1980s) on the composition of plant cell walls, with a
      description of the polysaccharides contained in the microfibrillar and amorphous
      phases: cellulose, hemicellulose and pectic substances, as well as the other
      components: lignin, proteins and enzymes. Cellulose is a linear homopolymer made
      up of microfibrils that form a para-crystalline structure stabilised by hydrogen
      bridges. The hemicelluloses constitute an important group of polysaccharides,
      which are inter-linked and also linked to microfibrils of cellulose and/or
      pectins, the most important being: xylans, arabinoxylans, mannans,
      galactomannans, glucomannans, arabinogalactan II, beta-1,3-glucan and beta-1,3
      beta-1,4-glucans. The pectic substances are a complex mixture of colloidal
      polysaccharides that can be extracted from the cell wall with water or chelating
      agents, the most significant being: rhamnogalacturonan I, rhamnogalacturonan II,
      arabinan, galactan, arabinogalactan I and D-galacturonan.

PMID- 7732731
TI  - Pasteurization of food by hydrostatic high pressure: chemical aspects.
AB  - Food pasteurized by hydrostatic high pressure have already been marketed in
      Japan. There is great interest in this method also in Europe and USA. Temperature
      and pressure are the essential parameters influencing the state of substances
      including foods. While the influence of temperature on food has been extensively
      investigated, effects of pressure, also in combination with temperature, are
      attracting increasing scientific attention now. Processes and reactions in food
      governed by Le Chatelier's principle are of special interest; they include
      chemical reactions of both low- and macromolecular compounds. Theoretical
      fundamentals and examples of pressure affected reactions are presented.

PMID- 7732732
TI  - Investigations into the oral lead exposure of adults in the former German
      Democratic Republic.
AB  - The lead content of a representative assortment of foodstuffs and drinking water
      as well as the lead intake of adults were systematically investigated in 1988 in
      order to judge the oral lead exposure of the inhabitants of the former German
      Democratic Republic (GDR). The foodstuffs as well as the drinking water contained
      normal lead concentrations. Levels exceeding the limits set by the Federal Office
      of Health and the Decree on Drinking Water were not obtained. The lead intake was
      34 micrograms/day in adult men and 25 micrograms/day in adult women according to
      the results of the basket study, amounting to 11-13% of the PTWI provisional
      tolerable weekly intake value of lead. An oral lead exposure of the adult
      population in the former GDR can be excluded.

PMID- 7732733
TI  - Storage stability of cooked sausages containing vegetable oils.
AB  - Comminuted cooked sausages were produced using standard industrial practices, by
      substituting corn oil, sunflower oil, cotton seed oil, soybean oil and
      hydrogenated vegetable fat for animal fat. When processed, products were assessed
      for their stability with respect to autoxidation and change in organoleptic
      properties during vacuum-packed storage in a domestic refrigerator at 4 degrees
      C. Data obtained indicated that changes in thiobarbituric acid (TBA) values and
      organoleptic properties of products produced using corn oil, sunflower oil and
      hydrogenated vegetable fat were similar to those observed for reference material
      produced using lard. In the case of samples produced using soybean and cotton
      seed oil, TBA value changes were more pronounced, but did not exceed acceptable
      limits. A more rapid deterioration of organoleptic characteristics was also
      observed for the same samples, which showed flavour problems after 3 months of
      storage at 4 degrees C. Substitution of plant oils for lard considerably reduced
      the cholesterol content and increased the ratio of unsaturated to saturated fatty
      acids of cooked sausages.

PMID- 7732734
TI  - L-ascorbic acid in nonenzymatic reactions. I. Reaction with glycine.
AB  - The influence of the water content, molar ratio, time and temperature on the
      formation of nondialysable melanoidins produced by the interaction of L-ascorbic
      acid and glycine has been studied. The isolated polymers have been characterized
      by spectrum analysis and fractionated using gel chromatography. The rate
      constants of the reaction for temperatures of 90 degrees C, 100 degrees C and 110
      degrees C have been calculated and are (0.84 +/- 0.29) x 10(-5) x s-1, (1.33 +/-
      0.14) x 10(-5) x s-1 and (5.30 +/- 0.37) x 10(-5) x s-1, respectively. The
      activation energy of the reaction has been determined to be 106.07 +/- 32.47
      kJ/mol.

PMID- 7732735
TI  - An ultrastructural study of pulmonary bronchiolar and alveolar epithelium in
      sheep.
AB  - The cellular population lining the bronchiolar and alveolar epithelium of the
      lower respiratory tract of three clinically healthy, purebred Suffolk lambs of
      both sexes and 3-4 months old was studied using a transmission-electron
      microscope. The epithelium of primary and secondary bronchioles consisted of four
      cell types: basal cells, intermediate cells, ciliated cells, and non-ciliated
      (Clara) cells, whereas the epithelium of terminal and respiratory bronchioles
      consisted of only two kind of cells: ciliated and Clara cells. The alveolar wall,
      including alveolar ducts and saccules, was covered by type I and type II
      pneumocytes. In addition, the presence of pulmonary intravascular macrophages was
      a constant in most of the alveolar capillaries. The morphologic characteristics
      of all these cells are described in detail and discussed.

PMID- 7732736
TI  - [Measuring fibrinogen concentrations in healthy dogs: standardization, comparison
      of methods and reference values].
AB  - Plasma fibrinogen concentration was measured in 67 healthy, adult dogs using five
      different methods (gravimetry, methods described by JACOBSSON (1955) RATNOFF and
      MENZIE (1951), and CLAUSS (1957), and functional photometric assay). Apart from
      using linear regression and the Pearson correlation coefficient (r) in order to
      characterize the relation between different methods, reference ranges (2.5-97.5%
      fractile) were calculated for all methods. For calibration of the CLAUSS method
      (1957) and the photometric assay, dog plasma with a defined fibrinogen
      concentration was used. Measurements of commercial human fibrinogen standards
      yielded a good conformity with the concentrations specified by the manufacturer
      (values approximately 3% too low). These standards appear, therefore, to be also
      suited to the calibration of measurements of dog fibrinogen. The reference range
      for the gravimetry was 1.08-2.88 g fibrinogen per litre of plasma. A considerable
      conformity and close correlation was seen between the fibrinogen concentration
      measured by gravimetry and by using methods described by JACOBSSON (1955; y =
      1.088 x -0.142, r = 0.967) or CLAUSS (1957; y = 0.999 x -0.004, r = 0.973),
      respectively. Between the reference-method gravimetry and the photometric method
      and RATNOFF-MENZIE (1951) method, respectively, a less close correlation, as well
      as a minor conformity, was found.

PMID- 7732737
TI  - Histological and immunohistological classification of canine glomerular disease.
AB  - A histological and immunohistological study of the kidneys of 115 dogs, with and
      without clinical signs of spontaneous renal disease, was performed to prove the
      applicability of the WHO criteria for the classification of human glomerulopathy.
      Aside from the morphological investigation of paraffin and resin semithin
      sections, deposits of immunoglobulins, the complement component C3, and
      fibrinogen were observed immunoenzymatically in paraffin-embedded tissue
      specimens. From this, eight different types of glomerular lesions with various
      frequencies were identified: minor glomerular abnormalities (28 cases), focal and
      segmental hyalinosis and sclerosis (12 cases), focal glomerulonephritis (GN; 18
      cases), diffuse membranous GN (nine cases), diffuse mesangial proliferative GN (2
      cases), diffuse endocapillary proliferative GN (five cases), diffuse
      mesangiocapillary GN (25 cases), diffuse sclerosing GN (11 cases) und
      unclassified GN (two cases). In one case, renal dysplasia was diagnosed and two
      dogs did not present glomerular alterations. The results are discussed with
      regard to human glomerular diseases and pathogenic mechanisms.

PMID- 7732738
TI  - Effects of drastic changes in P intake on P concentrations in blood and rumen
      fluid of lactating ruminants.
AB  - The course of inorganic-phosphate (Pi) concentrations in blood plasma and serum
      were determined in lactating ruminants when P intake was changed abruptly from
      adequate, during a control period, to very low in a period of P depletion, and
      back to adequate during a period of P repletion. In each of three trials, four or
      three goats and, in one trial, four cows were used. In addition, the course of P
      concentration in the rumen fluid of three fistulated goats was studied. Pi
      concentrations in plasma or serum started to fall immediately with changing P
      intake from adequate to low, reaching a minimum plateau of less than 0.25 mM in
      three trials and 0.4 mM in one trial. Correspondingly, concentrations rose
      instantly with return of P intake to adequate, overshooting the range observed in
      goats during the control period and then returning to normal. P concentrations in
      particle-free rumen fluid declined from about 30 mM in the control period to 5.7
      mM during P depletion and returned to 30 mM during P repletion, paralleling the
      respective course of Pi in blood plasma.

PMID- 7732739
TI  - Effect of protein and fat content in feed on plasma alanine-aminotransferase and
      hepatic fatty infiltration in mink.
AB  - The effect of the content of protein and fat in the feed on the development of
      fatty infiltration of the liver in the period from weaning until pelting was
      measured in two groups of male scanblack mink (Mustela vision) fed 20% and 45%,
      respectively, of metabolizable energy (ME) from protein. Furthermore, plasma
      activity of alanine-aminotransferase and the content of specifically chosen
      clinical-chemical variables in the blood were measured. At pelting time in
      December, the liver weights were absolutely and relatively heavier to body weight
      and had a considerably higher fat content at 20% of ME from protein than at 45%
      of ME from protein. From August to pelting time, the activity of alanine
      aminotransferase in plasma was higher at a low protein level than at a higher
      protein level in the feed. It is concluded that the content of protein and fat in
      the feed affects the incidence of hepatic fatty infiltration in mink. In the
      growth period, it is possible, based on plasma activity of alanine
      aminotransferase, to select animals with histological fatty infiltration of the
      liver.

PMID- 7732740
TI  - Blood levels of the prostaglandin F2 alpha metabolite during the postpartum
      period in Bos indicus cows in the humid tropics.
AB  - Plasma levels of the prostaglandin F2 alpha metabolite (15
      ketodihydroprostaglandin F2 alpha) were determined by radioimmunoassay in 26
      postpartum multiparous Brahman cows. Variation in the concentrations of the
      metabolite was high among animals. 15-Ketodihydro-PGF2 alpha concentrations on
      day 0, 5, 10, 15 and 20 postpartum ranged from 402 to > or = 1000, from 251 to >
      or = 1000, from 237 to > or = 1000, from 75 to 608 and from 75 to 267 pmol l-1,
      respectively. The prostaglandin metabolite levels were elevated at parturition
      and remained elevated thereafter for periods varying up to 10 to 23 days
      postpartum (16.7 +/- 0.7 days, mean +/- SEM). Uterine involution (UI) was
      completed by 28.0 +/- 0.8 days (ranging from 20 to 36 days). A markedly linear
      decrease of 15-ketodihydro-PGF2 alpha levels (P < 0.001) occurred from
      parturition until Day 23 postpartum. A significant correlation between the
      duration of the elevated PGF2 alpha metabolite and the time required for
      completion of UI was observed (r = -0.05, P < 0.01). The effect of parity (PT) on
      15-ketodihydro-PGF2 alpha levels was not significant, however the relationship
      between UI and PT was affected (r = -0.59, P < 0.001). Both PGF2 alpha release
      and PT had effects on the variability of UI (R2 = 0.62, P < 0.001). No
      significant relationship was found between elevated levels of 15-ketodihydro-PGF2
      alpha UI and PT with postpartum anoestrous interval (PPAI).

PMID- 7732741
TI  - Influence of the oestrous cycle on experimental intrauterine E. coli infection in
      the sow.
AB  - The influence of the oestrous cycle on the onset of endometritis in the sow was
      studied. Ten pubertal, unmated gilts of the Belgian Negative Landrace were used.
      Nine gilts were inoculated into the uterus by laparotomy with a suspension of an
      E. coli strain isolated from the uterus of a discharging sow from a herd having
      many problems with vaginal discharge and a lowered fertility. One gilt was as a
      control inoculated with 2 ml of a PBS-solution. All sows inoculated during
      dioestrus developed clinical symptoms, but only 1 of the 5 gilts inoculated at
      standing oestrus developed a vaginal discharge. These data confirm the hypothesis
      that the stage of the oestrous cycle has an important influence on the onset of
      endometritis. The resistance to E. coli infections was higher when the gilts were
      inoculated during oestrus.

PMID- 7732742
TI  - A comparative study of aerobic capacity and fitness in three different horse
      breeds (Andalusian, Arabian and Anglo-Arabian).
AB  - Aerobic capacity and fitness was studied in three different horse breeds
      (Andalusian, Arabian and Anglo-Arabian) using a four-level exercise test of
      gradually increasing intensity (15, 20, 25 and 30 km/h). The lactate
      concentration at the first three exercise levels was significantly lower for
      Arabian and Anglo-Arabian horses relative to Andalusian horses, but similar for
      the three breeds at the last level. Arabian and Anglo-Arabian horses reached a
      higher rate than Andalusian horses at plasma lactate concentration of 2 mmol/l
      (VLA2) and 4 mmol/l (VLA4). Andalusian horses exhibited a significantly lower
      heart rate at rest than the other two breeds, but the differences virtually
      disappeared at 15 km/h. At 20 km/h, Andalusian horses reached a higher heart rate
      than Arabian and Anglo-Arabian horses; at 25 km/h, however, their heart rate only
      exceeded that of Anglo-Arabian horses. Finally, no significant differences
      between breeds were observed at 30 km/h. No differences between breeds as regards
      heart rate were found if this was expressed as a function of lactate plasma
      concentrations of 2 mmol/l (HRLA2) and 4 mmol/l (HRLA4). At a heart rate of 150
      (VHR150) and 200 beta/min (VHR200), Andalusian horses achieved the lowest speeds.

PMID- 7732743
TI  - Ultrasonography of the bovine postpartum uterus with retained fetal membranes.
AB  - The aim of this study was to describe the potential application of ultrasound in
      combination with the rectal palpation method and to compare the results to
      determine the involution period in 11 Swedish dairy cows with retained fetal
      membranes (RFM). The animals were examined three times a week during the first 8
      week postpartum (PP) period. Significant quantity of abnormal vaginal discharges
      with concomitant accumulation of snowy fluid and thickening of the endometrial
      and uterine walls were interpreted as evidence of endometritis. The discharges
      decreased most markedly during the third week PP concomitantly with a marked
      decrease in the cervical and uterine size. Resumption of cyclical ovarian
      activity occurred within a month in 7 animals. Five of these cows had 2
      ovulations and two animals had 1 and 3 ovulations, respectively. A slight
      increase of the cervix and uterine size was observed in all ovulating animals in
      relation to the oestrous periods. Several different calculation methods of the
      ultrasonographic results were evaluated to describe the completion of uterine
      involution and compared with findings at rectal palpation. The best congruency
      with rectal palpation was found to use a 0.5 cm difference for comparison of the
      previous pregnant and non-pregnant uterine horns in singleton cows and an 80%
      reduction of the uterine size in all studied animals.

PMID- 7732744
TI  - Intrauterine bacterial findings in postpartum cows with retained fetal membranes.
AB  - Eleven Swedish postpartum cows with retained fetal membranes (RFM) were studied
      to determine the intrauterine bacterial flora. Bacteriological examination was
      performed from twice weekly uterine biopsies. A total of 161 biopsies were
      collected during the first 8 weeks postpartum of which 82 (50.9%) were found with
      bacterial growth. Seventy-one of the 82 bacteria-positive biopsies (86.6%) showed
      mixed infections whereas the remaining 11 (13.4%) were pure cultures. Generally,
      a total of 322 isolates belonging to 12 different genera of bacteria, 6
      facultative and 6 obligate anaerobic pathogens were identified. Mixed infections
      were most frequent for Actinomyces pyogenes together with obligate anaerobic
      bacteria, especially Bacteroides levii/spp. and Fusobacterium necrophorum. All of
      the studied cows had an infection that involved the first two genera of bacteria,
      whereas F. necrophorum was found in 8 of the 11 animals. The present work
      suggests that a possible pathogenic synergism between A. pyogenes and the two
      main Gram-negative anaerobes might have caused early endometritis and/or
      persistent infection.

PMID- 7732745
TI  - Influence of anti-inflammatory drugs on adhesion of neutrophils to endothelial
      cells cultured on microcarriers: a novel in vitro system as an alternative to
      animal experimentation.
AB  - Pharmacological control of inflammation by steroidal (SAIDs) and nonsteroidal
      (NSAIDs) antiinflammatory drugs is of substantial clinical importance. To reduce
      the number of animals used in pharmacological and toxicological evaluation of
      these drugs we developed a novel assay to determine adhesion of bovine
      neutrophils (PMN) to bovine aortic endothelial cells (BAEC) cultured on
      microcarriers in a flow-through system. Pretreatment of BAEC with thrombin (10(
      7)-10(-4) M) led to a dose-dependent increase of PMN-adhesion (10(-6)-10(-4) M:P
      < 0.05); platelet-activating factor (10(-9) M) and 1:200 diluted zymosan
      activated serum (ZAS) had similar effects (P < 0.001). Pretreatment of PMN with
      SAIDs (50.9 and 509 microM dexamethasone, 12.2 and 24.4 microM flumethasone) did
      inhibit adhesion to ZAS-treated BAEC dose-dependently. Pretreatment of PMN with
      NSAIDs had a less consistent influence on adhesion to ZAS-stimulated BAEC. While
      phenylbutazone (0.33 and 3.3 mM), diclofenac (0.392 and 0.574 mM), indomethacine
      (0.436 and 0.872 mM), and acetylsalicylic acid (3.47 and 16.94 mM) induced dose
      dependent inhibition of PMN-adhesion to ZAS-treated BAEC, piroxicam (0.377 and
      0.754 mM) inhibited PMN-adhesion strongly (P < 0.001) but not dose-dependently,
      and ketoprofene (0.614 and 1.228 mM) had no effect on PMN-adhesion. The method
      presented here is efficient for evaluating the pharmacological modulation of PMN
      interaction with endothelial cells, and useful for studying further aspects of
      endothelial cell biology.

PMID- 7732746
TI  - Effects of verapamil, sodium nitroprusside, tetrodotoxin and caffeine on the
      electrical transmural stimulation induced contraction in the reticular groove
      smooth muscle of adult cattle.
AB  - The effect of electrical transmural stimulation (ETS) on smooth muscle strips in
      the floor of reticular groove of adult cattle was studied. The mechanical
      activity of the muscle strips was recorded isometrically. ETS (4 ms, 5 s,
      supramaximal voltage) caused frequency dependent (2-30 Hz) contractions of this
      smooth muscle. An increase in cytoplasmatic free calcium concentration can be
      achieved by release of the cation from intracellular store sites or by an influx
      of extracellular Ca2+ through calcium channels. The contractile response of the
      muscle strips was inhibited about 66% when it was incubated in a calcium-free
      EGTA-containing solution. The excitatory effect of ETS was not antagonized by
      verapamil (10(-6) mol/l), sodium nitroprusside (10(-6) mol/l) or tetrodotoxin
      (10(-6) mol/l). The electrically-evoked contraction was inhibited strongly (92%)
      by caffeine (30 mmol/l). The contractions of the smooth muscle from the reticular
      groove smooth muscle are dependent on the concentration of free calcium in the
      cell cytosol. This response was intracellular Ca2+ ion dependent.

PMID- 7732747
TI  - Mechanism of recovery in esophageal epithelia of rats with severe zinc
      deficiency.
AB  - Forty-six rats fed a Zn-deficient diet for 18 days, were divided into three
      groups and treated with Zn-deficient diet (GI), a normal (Zn-adequate) diet (GII)
      or a pharmacological Zn therapy diet (GIII) for 3 days. For light and electron
      microscopy, samples were taken at times 0, 8, 12, 24 and 72 h after treatment. In
      treatment GI, at all times, all rats had esophageal parakeratosis. With treatment
      GII, there was a variable progression toward normalization of the epithelium at
      12 and 24 h. At 72 h there was almost complete recovery of normal epithelium. In
      treatment GIII at 8 h, large, light cells in the basal layer were shown to be
      present between dark cylindrical cells, a finding which was transitionary and
      disappeared at 12 h. Also, a thin keratinized layer was observed above the
      granular layer at 12 h. Recovery had progressed at 24 h and was complete after 72
      h. The results are discussed in terms of a potential role of Zn in the sequence
      of cytochemical events in epithelial differentiation.

PMID- 7732748
TI  - Sevoflurane and oxygen anaesthesia following administration of atropine-xylazine
      guaifenesin-thiopental in spontaneously breathing horses.
AB  - The effects of sevoflurane-oxygen anaesthesia at a light-surgical depth on
      clinically important features were evaluated in spontaneously breathing horses
      that received atropine, xylazine, and guaifenesin-thiopental. Mean end-tidal
      concentrations of sevoflurane ranged from 1.6 to 2.3% during 90 min maintenance.
      Recovery from anaesthesia was extremely rapid and smooth. Heart rates did not
      significantly change after anaesthesia. Arrhythmia was not observed. Mean
      arterial pressure (mean +/- SD) ranged from 86 +/- 17 to 98 +/- 5 mmHg during
      anaesthesia. Minute ventilation was low due to decreased respiratory rates during
      anaesthesia. Changes in arterial blood gases and pH demonstrated respiratory
      acidosis during anaesthesia. Haematological findings revealed haemodilution
      during anaesthesia. Serum potassium decreased slightly during anaesthesia, but
      other serum biochemical values did not significantly change for 7 days post
      anaesthesia. These results suggest that sevoflurane may be an effective inhalant
      anaesthetic which produces a rapid recovery from anaesthesia in horses.

PMID- 7732749
TI  - Type I congenital cystic adenomatoid malformation of the lungs in a Hereford
      calf.
AB  - A 3-day-old Hereford calf was presented for general weakness and severe dyspnoea.
      Lateral radiographs projections showed several compartmentalized gas filled
      structures in the caudodorsal thorax. At necropsy each diaphragmatic lung lobe
      contained a large cyst. Gross and histopathologic findings were consistent with a
      congenital type I cystic adenomatoid malformation of the lungs.

PMID- 7732750
TI  - Effects of a low sodium diet with a high potassium content on plasma endothelin
      1, atrial natriuretic peptide and arginine vasopressin in normal dogs.
AB  - Eight clinically healthy male beagle dogs received a low sodium diet for 5 weeks.
      Before and after this period the dogs received a control diet for 3 weeks. Both
      diets provided the dogs with approximately 6.8 mmol K+/kg/day. Neither
      introducing nor withdrawing the low sodium diet changed the plasma concentrations
      of endothelin-1 (ET-1), atrial natriuretic peptide (ANP) and arginine vasopressin
      (AVP). Pooled data from the control periods were not different from the low
      sodium period for either ET-1 (2.31 pg/ml and 2.09 pg/ml, P = 0.21), ANP (42.51
      pg/ml and 38.99 pg/ml, P = 0.44) or AVP (4.14 pg/ml and 4.16 pg/ml, P = 0.91). It
      was concluded that ET-1, ANP and AVP in normal dogs are unaffected by a 6-fold
      change in sodium intake in the presence of a high potassium intake.

PMID- 7732751
TI  - Involvement of calcium in metallothionein synthesis.

PMID- 7732752
TI  - The cold shock response in microorganisms.

PMID- 7732753
TI  - Insect growth regulators. XXV. Chemical approach to the correlation of dynamic
      structure and biological activity of juvenile hormone analogues.
AB  - On the basis of flexibility of the carbon skeleton of a juvenoid molecule, an
      analysis of its steric properties required to induce a biological effect in
      insects Dysdercus cingulatus and Tenebrio molitor, is presented. Steric analyses
      of "branched" juvenoids and some derivatives of farnesoic acid differing in
      position of the double bonds, are also described.

PMID- 7732754
TI  - DNA damage and repair in normal and neoplastic cells treated with adriamycin.
AB  - Adriamycin (ADR), a common antineoplastic drug, was used to study DNA repair
      synthesis, cell cytotoxicity and DNA single strand breaks in normal human
      fibroblasts--CLV98 and human melanoma cells--ME18. No repair synthesis was
      observed in ME18 and CLV98 cells exposed to adriamycin in concentrations up to
      10(-5) M. ME18 cells were less sensitive to ADR treatment than CLV98 cells.
      Adriamycin-induced DNA single strand breaks (at ADR concentration: 1
      microgram/ml) were incompletely repaired in ME18 cells and unrepaired in CLV98
      cells within 24 h after drug removal. Within 48 h strand breaks were completely
      repaired in both kinds of cells. No repair of single strand breaks was observed
      in ME18 and CLV98 cells after drug treatment in the concentration of 5
      micrograms/ml.

PMID- 7732755
TI  - Substrate specificity of methylthioadenosine phosphorylase from human liver.
AB  - Methylthioadenosine (MTA) phosphorylase purified 615-fold from human liver
      cleaved phosphorolytically nucleoside analogues at the decreasing specific
      activity: 5'-deoxyadenosine > 5'-iodo-5'-deoxyadenosine > MTA > adenosine > 2
      chloroadenosine > 2-chloro-5'-O-methyl-2'-deoxyadenosine > 2-chloro-2'
      deoxyadenosine > > 2'-deoxyadenosine. Adenosine and analogues of 5'
      deoxyadenosine were strong competitive inhibitors of MTA phosphorolysis catalysed
      by the human liver enzyme.

PMID- 7732756
TI  - Purification and partial characterization of glutamine synthetase isoforms from
      Triticale seedlings.
AB  - Two isoforms of glutamine synthetase (EC 6.3.1.2), cytoplasmic (GS1) and
      chloroplastic (GS2) were isolated from shoots of 14-day-old Triticale seedlings,
      and purified 260-fold and 248-fold, respectively. Specific activities of the two
      preparations were 35.1 and 33.5 mumol x min-1 per mg of protein, respectively.
      Both crude extracts and homogeneous GS1 and GS2 preparations required divalent
      metal ions (Mg2+, Mn2+, Co2+) for their activities. Mg2+ was the most effective
      activator, the highest activity of GS1 being reached at 5 mM, and that of GS2 at
      20 mM MgCl2. The optimum pH for the two isoforms showed large differences,
      dependent also on the kind of divalent ion. Molecular masses of GS1 and GS2 were
      305000 Da and 385200 Da, respectively. It seems that native protein of GS1 is
      built from eight identical subunits of Mm 38000 Da and that of GS2 of the same
      number of subunits but of Mm of about 48000 Da. Proteins of GS isoforms differed
      significantly in their amino-acid composition.

PMID- 7732757
TI  - Nucleotide sequence of RNA of a Polish isolate of potato leafroll luteovirus.
AB  - The nucleotide sequence of the genomic RNA of a Polish isolate of a potato
      leafroll virus was determined. Some variations between the determined sequences
      were observed. A comparison of the frequency of sequence variants in particular
      regions of the genome is presented.

PMID- 7732758
TI  - Effect of disulfide and sulfhydryl reagents on abortive and productive elongation
      catalyzed by Escherichia coli RNA polymerase.
AB  - The effect of disulfide and sulfhydryl reagents on the rate of abortive and
      productive elongation has been studied using Escherichia coli RNA polymerase
      holoenzyme and poly[d(A-T)] as template. In the presence of UTP as a single
      substrate and UpA as a primer, the enzyme catalyzed efficiently the synthesis of
      the trinucleotide product UpApU. Incubation of RNA polymerase with 1 mM 2
      mercaptoethanol resulted in a 5-fold increase of the rate of UpApU synthesis. In
      contrast, incubation of the enzyme with 1 mM 5,5'-dithio-bis(2-nitrobenzoic) acid
      resulted in a 6-fold decrease of the rate of abortive elongation. Determination
      of the steady state kinetic constants associated with UpApU synthesis disclosed
      that the disulfide and sulfhydryl reagents mainly affected the rate of UpApU
      release from the ternary transcription complexes and therefore influenced the
      stability of such complexes.

PMID- 7732759
TI  - Purification and characterization of the protein kinase eEF-2 isolated from rat
      liver cells.
AB  - The elongation factor 2 (eEF-2) protein kinase was isolated from rat liver cells,
      purified and partly characterized. It was found that the enzyme exists in an
      inactive form in the homogenate of rat liver. The active fraction of kinase eEF-2
      was obtained after removal of the inhibitory substance by hydroxyapatite column
      chromatography. The purified enzyme is an electrophoretically homogeneous protein
      with relative molecular mass of approximately 90,000 and isoelectric point, pI =
      5.9. The enzyme specifically phosphorylates the elongation factor eEF-2 in the
      presence of calmodulin and Ca2+.

PMID- 7732760
TI  - Differences in nonenzymatic glycation of histones.
AB  - Time course of glucose binding by histone Hl and total histones was followed in
      isolated histone preparations and in thymus nuclei. In both cases the uptake of
      glucose by Hl was surprisingly high in contrast to a much lower uptake of glucose
      by total histones. DNA is not implicated in glycation of histones in nuclei.

PMID- 7732761
TI  - Organization of the 18S, 5S, 4S rRNA genes and the tRNA-like repeat in the
      mitochondrial genomes of three lupin species.
AB  - Southern blots of mitochondrial (mt) DNAs of three Lupinus species cleaved with
      three restriction enzymes were probed with Lupinus luteus mtDNA fragments
      containing 18S, 5S rRNA genes or a tRNA-like repeat. Comparison of the number of
      hybridizing bands and their intensity suggested that the mt 18S and 5S rRNA genes
      occur mostly in one copy in the genomes of three lupin species. The exception
      concerned the Lupinus angustifolius 5S rRNA gene showing two hybridizing bands of
      unequal intensity. The results of hybridization of the lupin mitochondrial
      genomes with a probe specific for the Lupinus luteus tRNA-like repeat pointed to
      the presence of such a repeat in other parts of the genomes besides the vicinity
      of the 18S rRNA gene. Northern hybridization analysis showed the presence of 18S,
      5S and tRNA-like repeat transcripts similar in size in all lupin species.

PMID- 7732762
TI  - maf1 mutation alters the subcellular localization of the Mod5 protein in yeast.
AB  - Two forms of Mod5p, a tRNA modification enzyme, are found in three intracellular
      compartments, mitochondria, cytoplasm and nucleus, but are encoded by a single
      MOD5 gene. The two forms of the enzyme, Mod5p-I and Mod5p-II differ at the N
      termini and are produced by initiation of translation at different start codons.
      Mod5p-I does contain a mitochondrial targeting signal and is distributed between
      mitochondria and cytoplasm, whereas Mod5p-II is found in the cytosol and nucleus
      (Boguta, M., et al. 1994, Mol. Cell. Biol. 14, 2298-2306). In the present work
      mutants which mislocalize the Mod5p-I enzyme were isolated. The screen was based
      on a correlation between the amount of cytosolic protein and the efficiency of
      tRNA mediated suppression. Identification of mutants is possible because a red
      pigment accumulates in the cells unable to suppress an ade2-1 nonsense allele.
      The maf1 mutant, with an altered intracellular localization of the Mod5p-I
      protein, was isolated. Immunofluorescence data suggest that the mutation causes
      mislocalization of the Mod5p-I to the nucleus.

PMID- 7732763
TI  - How many 5S rRNA genes and pseudogenes are there in Aspergillus nidulans?
AB  - We have estimated the number of 5S rRNA genes in Aspergillus nidulans using two
      dimensional agarose gel electrophoresis and hybridization to appropriate probes,
      representing the 5'-halves, the 3'-halves of the 5S rRNA sequence and a sequence
      found at the 3'-end of all known A. nidulans pseudogenes (block C). We have found
      23 5S rRNA genes, 15 pseudogenes consisting of the 5'-half of the 5S rRNA
      sequence (of which 3 are flanked by block C) and 12 copies of block C which do
      not seem to be in the vicinity of 5S rRNA sequences. This number of genes is much
      lower than our earlier estimates, and makes our previously analyzed sample of 9
      sequenced genes and 3 pseudogenes much more representative.

PMID- 7732764
TI  - Basic properties of the pyruvate dehydrogenase complex isolated from aurochs
      heart.
AB  - The purified aurochs (Bison bonasus, European bison) heart pyruvate dehydrogenase
      complex (PDC) has a set of subunits typical of mammalian PDC. PDC from aurochs
      heart contains firmly bound tiamine pyrophosphate in the amount providing over
      50% of the maximal activity of the complex. The apparent value for activation
      energy of PDC is 60 kJ/mol. The Michaelis constant values for aurochs heart PDC
      are 22.4 +/- 1.0, 3.3 +/- 0.1 and 24.4 +/- 3.6 microM for pyruvate, CoA and NAD,
      accordingly. Acetyl-CoA is a competitive inhibitor with respect to CoA (Ki = 14.2
      +/- 0.4 microM), whereas NADH gives the same inhibition with respect to NAD (Ki =
      46.9 +/- 10.0 microM). The Km for CoA and NAD of the aurochs heart PDC are lower
      than that of domestic animals PDC.

PMID- 7732765
TI  - Purification of arginase from Aspergillus nidulans.
AB  - Arginase (EC 3.5.3.1) of Aspergillus nidulans, the enzyme which enables the
      fungus to use arginine as the sole nitrogen source was purified to homogeneity.
      Molecular mass of the purified arginase subunit is 40 kDa and is similar to that
      reported for the Neurospora crassa (38.3 kDa) and Saccharomyces cerevisiae (39
      kDa) enzymes. The native molecular mass of arginase is 125 kDa. The
      subunit/native molecular mass ratio suggests a trimeric form of the protein. The
      arginase protein was cleaved and partially sequenced. Two out of the six
      polypeptides sequenced show a high degree of homology to conserved domains in
      arginases from other species.

PMID- 7732766
TI  - Digoxigenin-labelled molecular probe for the simultaneous detection of three
      potato pathogens: potato spindle tuber viroid (PSTVd), potato virus Y (PVY), and
      potato leafroll virus (PLRV).
AB  - A molecular probe, p3POT, was constructed of PSTVd, PVY, PLRV cDNA fragments
      introduced into pUC18 vector. Sequencing of the inserts revealed that cloned
      fragments covered conservative parts of pathogenic genomes. Dot-blot
      hybridization of digoxigenin-labelled construct to crude extracts from plants
      infected with different potato viruses proved high sensitivity and specificity of
      the p3POT probe. This makes p3POT probe an useful tool for the routine testing,
      and selection of virus-free potatoes.

PMID- 7732767
TI  - Development of myoclonus in patients with partial epilepsy during treatment with
      vigabatrin: an electroencephalographic study.
AB  - In the context of a study of the effects of gamma-vinyl-GABA (GVG) on seizure
      occurrence and on EEG abnormalities we present three cases with focal epilepsy in
      which new clinical and EEG paroxysmal manifestations were observed during GVG
      therapy. At that time, whereas an amelioration or no change in patients' habitual
      seizures were observed, myoclonic jerks appeared with related changes in the EEG
      paroxysmal abnormalities, represented by generalized polyspike and wave
      complexes. An electroclinical correlation was recorded in one case. These data
      indicate that, although occurring rarely, it is possible to have epileptic
      myoclonus during GVG treatment. Mechanisms underlying these manifestations are
      difficult to explain. Probably a shift in the anti/proconvulsant GABAergic
      balance towards the latter may compromise the therapeutic effect of GVG.

PMID- 7732768
TI  - Autonomic dysfunction in Alzheimer's disease.
AB  - Twenty-nine patients fitting the NINCDS-ADRDA criteria of Alzheimer's disease
      participated in a study of autonomic functions. A number of tests on
      parasympathetic and sympathetic functions were made. Eighteen of the patients
      were tested a second time one year later. Fifteen healthy subjects with no family
      history of dementia disorders served as controls. Compared to the controls, the
      patients showed signs suggesting autonomic dysfunction affecting parasympathetic,
      as well as vasomotor sympathetic, functions.

PMID- 7732769
TI  - Is sporadic MS caused by an infection of adolescence and early adulthood? A case
      control study of birth order position.
AB  - Birth order position was examined in 164 cases with sporadic multiple sclerosis
      (MS), i.e. no other family members with MS, and spousal controls, matched for
      sibship size, socioeconomic status and opposite sex. The results did not find an
      association between birth order position and the subsequent development of MS and
      thus do not support the concept of an infectious cause for MS where "early
      exposure" is protective and exposure to the infection is a single event of short
      duration.

PMID- 7732770
TI  - Combination total lymphoid irradiation and low-dose corticosteroid therapy for
      progressive multiple sclerosis.
AB  - Total lymphoid irradiation (TLI) has been reported to delay deterioration in
      patients with progressive multiple sclerosis and other autoimmune disorders.
      METHODS--In an open trial, the effect of TLI combined with a one year course of
      low dose prednisone was compared to the effect of sham TLI and TLI only in a
      prior double-blind study of patients with progressive multiple sclerosis. RESULTS
      -Twenty-seven patients receiving TLI combined with corticosteroids had
      significantly greater lymphocytopenia in the year post-therapy than those
      receiving TLI only or sham TLI and Kaplan Meier product-limit survival analysis
      showed significantly less progression in the TLI plus steroid group over 4 years
      of follow-up. No difference in lymphocytopenia or progression was found with TLI
      plus corticosteroid therapy when the spleen was removed from the field of
      irradiation. CONCLUSION--These results lend further support to the hypothesis
      that TLI may be effective in progressive MS, and indicates that adding low-dose
      prednisone may enhance this effect. The study also suggests that TLI may be
      equally effective whether or not the spleen is irradiated.

PMID- 7732771
TI  - Rehabilitation after stroke: predictive power of Barthel Index versus a cognitive
      and a motor index.
AB  - The aim of the present study was to investigate the predictive power of ratings
      of Barthel Index at Day 40 post stroke, compared with and/or combined with
      simultaneous ratings from a mobility scale (EG motor index) and a rather simple
      cognitive test scale (CT50). The parameter to be individually predicted was the
      need for special living facilities and support at discharge from a rehabilitation
      hospital, as well as six months later; 53 stroke patients with age median 68
      years were included in this prospective study. It was shown that a combination of
      Barthel Index and CT50 had a stronger predictive power than Barthel Index alone.
      A combination of EG motor index and CT50 had at least the same predictive power
      as the combination of Barthel Index and CT50. The usefulness of a simple diagram
      for individual prognostication was demonstrated.

PMID- 7732772
TI  - Vertebrobasilar infarcts in patients with dolichoectatic basilar artery.
AB  - We reported 18 patients who had stroke in the posterior circulation with
      dolichoectatic basilar artery. TIAs preceded posterior circulation infarct in 5
      patients. Strokes involved medulla oblongata (3), pons (4), cerebellum (4),
      mesencephalon (4), thalamus or occipital lobe (3). Dolichoectatic basilar artery
      also produced hydrocephalus in one patient. The mechanism of stroke may be due to
      penetrating artery occlusion, basilar artery thrombosis or an embolism from the
      abnormal basilar artery. Short-term prognosis was poor seeing that 4 patients
      died within 12 days of stroke.

PMID- 7732773
TI  - Isolated acute vertigo in the elderly; vestibular or vascular disease?
AB  - INTRODUCTION: Elderly patients with isolated acute vertigo are commonly
      encountered in clinical practice, but little is known about the underlying cause
      of the symptoms. MATERIAL & METHODS: We prospectively studied 24 patients aged 50
      75 years with the acute onset of isolated vertigo lasting > 48 h and no
      abnormality on neurological examination other than nystagmus. The study protocol
      included neuro-imaging (MRI 22 patients, CT 2 patients), Doppler sonography, and
      electro-oculography. RESULTS: MRI/CT showed the presence of an infarction of the
      caudal cerebellum in six patients (25%), 3 of whom had a potential cardioembolic
      source and normal Doppler sonography findings, whereas 3 patients had ipsilateral
      vertebral artery occlusion and normal cardiac findings. MRI of the posterior
      fossa was normal in 18 patients. On electro-oculography, ataxic pursuit eye
      movements was a characteristic finding in patients with cerebellar infarction,
      whereas caloric test findings were not discriminative. CONCLUSION: A caudal
      cerebellar infarction may easily be misdiagnosed clinically as a labyrinthine
      disorder, and was found to be the cause in one fourth of patients presenting with
      isolated acute vertigo.

PMID- 7732774
TI  - Somatosensory evoked potentials in cerebral ischemia of rabbits.
AB  - Twenty-one rabbits were used in the ischemic group and six in the control group.
      Cerebral ischemia of variable degree was induced by Fe particle injection method.
      Somatosensory evoked potentials (SEPs) and cerebral blood flow (CBF) were
      compared when the CBF levels decreased to their minimum. The latency of the SEPs
      increased along with the decrease of the CBF when it was lower than 20 ml/100
      g/min (68% of the pre-ischemic control level). This may be related to the
      ischemic change of the white matter. The amplitude showed diphasic changes. When
      the CBF decreased below 20 ml/100 g/min, the amplitude increased; when the CBF
      was lower than 11 ml/100 g/min (38% of the pre-ischemic level), it decreased.
      These results indicate that the functions of the cerebral cortex might be excited
      in mild ischemia, and be suppressed in severe ischemia.

PMID- 7732775
TI  - Presence of Kluver-Bucy syndrome as a positive prognostic feature for the
      remission of traumatic prolonged disturbances of consciousness.
AB  - After severe brain injury a prolonged disturbance of consciousness may occur,
      sometimes with transient apallic syndrome (awakening without awareness of self
      and surroundings). Kluver-Bucy is described in the literature as a typical post
      traumatic remission phase, in which the patients show an increase of oral
      automatisms and/or of sexual drive. The study describes Kluver-Bucy syndrome as a
      sign associated with favourable prognosis in the outcome of traumatic
      disturbances of consciousness in survivors of head trauma. Seventy-seven patients
      who had suffered severe brain injury due to traffic accidents entered into the
      study. All had experienced a relatively benign clinical course since they
      recovered full awareness, that is were able to communicate with their relatives.
      The occurrence of prolonged coma, of apallic syndrome and of Kluver-Bucy syndrome
      are related to outcome date in regards to the patient's work and family function
      at a mean of 32 months later. In particular, the duration of the apallic syndrome
      (duration of unconsciousness) was significantly correlated with the global
      outcome of the patients (p < 0.001).

PMID- 7732776
TI  - Increased CSF C4d in demyelinating neuropathy indicates the radicular
      involvement.
AB  - Plasma and cerebrospinal fluid (CSF) levels of C4d and the circulating immune
      complex (CIC) to C1q were measured in 12 patients with chronic inflammatory
      demyelinating polyneuropathy and Guillain-Barre syndrome. CSF C4d values more
      than 2 SD from the mean of 8 cervical spongylosis cases were demonstrated in the
      patients with proximal demyelination. The CSF C4d probably originated from both
      intrathecal synthesis and the systemic circulation. CSF levels of C4d may serve
      as a sensitive indicator for the radicular involvement in demyelinating
      polyneuropathy.

PMID- 7732777
TI  - Early onset Alzheimer's disease in a South American pedigree from Argentina.
AB  - We report the clinical, SPET, immunohistochemical and DNA features of an early
      onset familial Alzheimer's disease (FAD) in an Argentine pedigree of South
      American indian ethnic background. Pedigree spans 5 generations comprising more
      than 110 biological relatives. Clinical data supported the diagnosis of early
      onset FAD (mean age at onset 38.9 years) in 10 family members, including 3 with
      pathological confirmation (mean age at death 48.5). The pattern of transmission
      suggested autosomal dominant inheritance. Prominent features were mood changes,
      early language impairment, myoclonus, seizures and cerebellar signs. SPET
      displayed bilateral frontal, temporo-parietal and cerebellar hypoperfusion in
      early stages and in an asymptomatic member at risk, suggesting that SPET may have
      predictive value in this family. Immunohistochemistry showed beta amyloid
      deposits within neuritic plaques and vessel walls and no anti-PrP
      immunoreactivity. DNA analysis showed no abnormalities in the beta amyloid
      precursor protein gene. The identification of additional genetic defects in well
      characterized independent FAD pedigrees will contribute to the understanding of
      the pathogenesis of Alzheimer's disease.

PMID- 7732778
TI  - Clinical heterogeneity in two pedigrees with the 3243 bp tRNA(Leu(UUR)) mutation
      of mitochondrial DNA.
AB  - We studied two pedigrees with a mutation at the nucleotide 3243 of mitochondrial
      DNA (mtDNA). The proband from the first pedigree had clinically defined MELAS
      plus maternally transmitted insulin-dependent diabetes mellitus (IDDM). The
      propositus of the other pedigree had exercise intolerance, lactic acidosis and
      ragged-red fibers (RRF). In the first pedigree, both the mother and the sister's
      proband harbored the point mutation in their muscle. The mother had 40% of mutant
      mitochondrial genomes and the sister 70%. In the second pedigree, the mutation
      was present in both muscle and blood from the proband as well as in blood from
      all other members studied. Proportion of mutant mtDNA was 90% in muscle and
      ranged from 40% to 90% in blood.

PMID- 7732779
TI  - SPECT imaging of gliomas with Thallium-201 and Technetium-99m-HMPAO.
AB  - Sequential Thallium-201 and Technetium-99m-HMPAO SPECT images were obtained from
      7 patients with high-grade gliomas and 5 patients with low-grade gliomas. The
      histo-pathological tumor-type was verified from either biopsy specimens or
      resected tissue from surgery. There was an intense uptake of Thallium-201 in all
      high-grade gliomas. Compared to the contralateral hemisphere the mean uptake was
      4.6 times higher. Low-grade gliomas showed only a marginally increased Thallium
      201 uptake (1.4 times). No overlap existed between the two groups. There was no
      correlation between Technetium-99m-HMPAO uptake and tumor type. Thallium-201
      appears to be a promising radiopharmaceutical for differentiating high- and low
      grade gliomas, whereas Technetium-99m-HMPAO is not.

PMID- 7732780
TI  - Suppressive effects of TNF-alpha on myelin formation in vitro.
AB  - Using organotypic cultures of ICR mouse cerebellum, we studied the effects of TNF
      alpha on myelin formation, and its demyelinating effects. Mature, myelinated
      cultures were resistant to TNF-alpha, even at the highest concentration examined,
      1 x 10(4) U/ml. However, when cultures were grown in medium containing TNF-alpha
      from the time of explantation, myelin formation was significantly affected at a
      concentration of 1 x 10(2) U/ml. The myelin sheaths formed were very thin,
      partial, and few in number. When TNF-alpha was removed from the medium within 6
      days, myelin formation was recovered. Although our in vitro system tests factors
      that influence myelin formation but not remyelination, these results suggest that
      TNF-alpha may be involved in the remyelination block following acute myelin
      breakdown.

PMID- 7732781
TI  - Stretch reflexes in Parkinson's disease.

PMID- 7732782
TI  - Interferon-gamma, interleukin-4 and transforming growth factor-beta mRNA
      expression in multiple sclerosis and myasthenia gravis.
AB  - BACKGROUND: Multiple sclerosis (MS) is characterized by perivascular inflammation
      and high levels of circulating T and B lymphocytes that respond to the myelin
      antigens myelin basic protein (MBP) and proteolipid protein (PLP), thereby
      suggesting a role for immunoregulatory cytokines. MATERIALS AND METHOD: Blood
      mononuclear cells (MNC) were prepared from patients with MS, optic neuritis (ON),
      myasthenia gravis (MG), other inflammatory (OIND) and non-inflammatory
      neurological diseases (OND), and from patients with HIV infection and healthy
      controls. MNC expressing cytokine mRNA were detected by in situ hybridization
      with radiolabelled cDNA oligonucleotide probes. Numbers of cytokine mRNA
      expressing cells were presented per standard numbers of MNC. RESULTS: MS patients
      had elevated numbers of MNC in blood expressing T helper type 1 (Th1) cell
      related interferon-gamma (IFN-gamma), Th2 cell associated interleukin-4 (IL-4)
      and the endogenously produced immunosuppressant transforming growth factor-beta
      (TGF-beta). IFN-gamma and TGF-beta correlated with MS disability: EDSS score < 3
      was associated with high numbers of TGF-beta mRNA positive cells while IFN-gamma
      mRNA positive cells tended to be low. The reverse was seen in patients with EDSS
      > or = 3. Cultures of MNC in presence and absence of antigen revealed that MBP
      and PLP induced strong responses in MS reflected by high levels of IFN-gamma, IL
      4 and TGF-beta mRNA expressing cells. Recombinant (r) TGF-beta 1 dose-dependently
      suppressed MBP-induced upregulation of the proinflammatory cytokines IFN-gamma,
      IL-4, IL-6, tumor necrosis factor-alpha, (TNF-alpha), TNF-beta and perforin, but
      not of the immunosuppressive and probably advantageous IL-10. Cytokine mRNA
      expressing cells were enriched in the MS patients' cerebrospinal fluid, as were
      the cytokine mRNA positive cells detected after culture in presence of MBP and
      PLP, reflecting an autonomy of the immune response in this compartment. ON, in
      many instances representing early MS, did not differ from clinically definite MS
      regarding profiles of IFN-gamma, IL-4 and TGF-beta. Also patients with MG had
      elevated numbers of IFN-gamma, IL-4 and TGF-beta mRNA expressing blood MNC. They
      were further augmented upon culture of the MG patients' MNC in presence of
      acetylcholine receptor (AChR). An upregulation of AChR-induced TGF-beta was
      observed in thymectomized patients. rTGF-beta suppressed AChR-induced
      upregulation of proinflammatory cytokines but not IL-10. Elevated numbers of IFN
      gamma, IL-4 and TGF-beta mRNA expressing blood MNC were also found in patients
      with OIND (aseptic meningo-encephalitis, chronic inflammatory demyelinating
      polyneuropathy, polymyositis, Eaton-Lambert syndrome) and in HIV-infected
      patients. In HIV infection, numbers of IL-4 mRNA positive cells correlated
      inversely with CD4+ cell counts, reflecting the involvement of IL-4 in later
      stages of the disease. Patients with non-inflammatory neurological diseases and
      healthy subjects had either no or low numbers of IFN-gamma, IL-4 and TGF-beta
      mRNA expressing cells when blood MNC were examined without previous culture, and
      after culture in presence and absence of MBP, PLP and AChR as antigens. An
      exception was a healthy pregnant lady who showed high levels especially of IL-4
      and IL-10 mRNA expressing cells, probably reflecting pregnancy-associated
      upregulation of Th2 cell related cytokines. Numbers of myelin antigen- and AChR
      reactive IFN-gamma and IL-4 mRNA expressing cells were also elevated, implicating
      upregulation of natural T cell autoimmunity in normal pregnancy. CONCLUSION: High
      numbers of in vivo activated and of organ-specific antigen-responsive Th1 and Th2
      like cells expressing IFN-gamma and IL-4 mRNA are characteristic for MS and MG.
      Upregulation of TGF-beta in MS patients with little disability and in MG after
      thymectomy implicates that TGF-beta has desirable effects in human diseases with
      autoimmune background.

PMID- 7732783
TI  - Identification of the characteristic vascular changes in a sural nerve biopsy of
      a case with cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL).
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy' (CADASIL) has recently been identified as a hereditary
      disorder with characteristic fine structural changes of small intracerebral
      arteries and arterioles. Electron microscopically there are characteristic
      perivascular deposits of granular electron-dense material resembling
      immunoglobulin deposits. The present case from a family with four affected
      members in three successive generations shows that similar vascular changes as
      described in the central nervous system are present in blood vessels of the sural
      nerve, although less pronounced and, therefore, affording electron microscopy for
      their unequivocal detection. Nevertheless it has been shown for the first time
      that the diagnosis of CADASIL can be verified by a sural nerve biopsy. Occasional
      focal accumulation of pinocytotic vesicles opposite the granular deposits
      suggests exocytosis as one of the possible pathomechanisms for their production.

PMID- 7732784
TI  - Neuronal cell loss in the dorsal raphe nucleus and the superior central nucleus
      in myotonic dystrophy: a clinicopathological correlation.
AB  - A quantitative study of neurons in the dorsal raphe nucleus (DRN) and the
      superior central nucleus (SCN) was performed in seven patients with myotonic
      dystrophy (MyD), five of whom showed hypersomnia, and in eight age-matched
      controls. The densities of neurons in the DRN and the SCN were significantly
      lower in MyD patients with hypersomnia than in MyD patients without hypersomnia
      and control subjects. There was an appreciable positive correlation in the
      density of neurons between the DRN and the SCN in all MyD patients. These data
      suggest that the neuronal loss of the DRN and the SCN is associated with the
      presence of hypersomnia in MyD.

PMID- 7732785
TI  - Periodic acid-Schiff (PAS)-positive deposits in brain following kainic acid
      induced seizures: relationships to fos induction, neuronal necrosis, reactive
      gliosis, and blood-brain barrier breakdown.
AB  - Periodic acid-Schiff (PAS)-positive deposits have been demonstrated in the
      central nervous system (CNS) of patients suffering from a wide variety of
      neurodegenerative disorders including Alzheimer's disease, presenile dementia,
      Parkinson's disease, diabetes mellitus, myoclonic epilepsy, and cerebral palsy.
      The etiology of these deposits and their relationship to mechanisms of
      progressive neurodegeneration is unknown. In the present study, we demonstrate
      that the kainic acid model of limbic status epilepticus provides a useful system
      for the study of PAS-positive staining. The relationship between PAS-positive
      deposition, induction of fos-like immunoreactivity (FLI), neuronal necrosis,
      reactive gliosis, and blood-brain barrier breakdown following the kainic acid
      induction of status epilepticus was investigated. Epileptiform activity was
      elicited in rats by intraperitoneal administration of 10 mg/kg kainic acid and
      brains were examined 3, 5, 12, 24, 72, and 168 h after drug injection. Four
      distinct types of PAS-positive staining in rat brain were observed: type 1,
      extracellular matrix (ECM) or blood vessel associated-material; type 2, granular
      deposits; type 3, glial labelling; and type 4, neuronal labelling. Results
      demonstrated that the four types of PAS-positive staining were differentially
      associated with specific markers of neuropathology: (1) type 1 ECM staining and
      type 3 glia were preferentially localized to edematous tissue; (2) the majority
      of type 3 glia were identified as reactive astrocytes, while a minority of
      appeared to be proliferating microglia; (3) type 1 blood vessels labelled
      hemorrhaging vasculature; (4) early deposition of type 2 granules was predictive
      of subsequent cell loss; (5) chronic type 2 granular deposits and type 4 neuronal
      labelling not associated with cell death could be predicted by early changes in
      FLI; and (6) chronic deposition of all four forms of PAS-positive material was
      correlated with earlier, transient blood-brain barrier compromise. The results
      support the growing literature that local carbohydrate metabolism may be one of a
      constellation of parameters important to the development of progressive
      neurodegeneration.

PMID- 7732786
TI  - Chordomas: pathological features; ploidy and silver nucleolar organizing region
      analysis. A study of 36 cases.
AB  - Chordomas are slow growing malignant neoplasms with a prolonged clinical course
      which do not usually metastasize. They are histologically benign, locally
      invasive and often recur following resection. Survival has been shown to vary
      widely and prognostic indicators have been difficult to identify. Cellularity,
      mitotic activity and cellular pleomorphism have not been found to have prognostic
      significance. Thirty-six cases of clival, cervico-thoracic and sacral chordomas
      were evaluated utilizing four variables as possible predictors of survival: (1)
      silver nucleolar organizing region (AgNOR), (2) ploidy, (3) fibrosis, and (4)
      inflammatory response. AgNOR areas in approximately 200 cells per case were
      calculated and summed. DNA ploidy was obtained in 23 of the cases by analyzing
      deparaffinized Feulgen-stained tissue. Fibrosis and inflammation were evaluated
      by hematoxylin and eosin and by trichrome stains. Clinical follow-up was
      available in the 36 cases with survival ranging from 0.5 to 159 months. A
      statistical analysis employing the Cox-Proportional Hazards model disclosed no
      significant correlation between AgNOR area and clinical outcome (P > 0.05). The
      variables, fibrosis, and inflammation, did not demonstrate prognostic
      significance (P > 0.05). Ploidy demonstrated a statistical trend for prognostic
      significance (P = 0.077). It is apparent that three of the four parameters
      studied do not independently affect survival. Although AgNOR has proved useful in
      the study of other neoplasms such as those of breast, prostate and bladder, it is
      not of significant importance in predicting the behaviour of chordomas. Ploidy,
      on the other hand, may be of value in predicting clinical outcome in chordomas
      and may be a useful marker in the evaluation of the aggressive biological
      behavior of these neoplasms.

PMID- 7732787
TI  - Mitochondrial dysfunction in adult-onset myopathies with structural
      abnormalities.
AB  - Three patients with chronic progressive external ophthalmoplegia of adult-onset,
      generalized muscle atrophy and myalgia are described. Two patients fulfilled the
      histological criteria for centronuclear myopathy, the third those for fiber-type
      disproportion. Additionally, typical ragged red fibers were found in all muscle
      specimens, and several muscle fibers were cytochrome c oxidase negative. NADH and
      succinate dehydrogenase stains showed increased subsarcolemmal accumulation of
      mitochondria. To determine whether these findings are coincidental or whether
      they indicated an additional mitochondrial disorder, all patients were
      investigated using biochemical analysis of the respiratory chain, molecular
      genetics, magnetic resonance spectroscopy of quadriceps muscle and ergometry.
      These tests suggested an additional mitochondrial dysfunction. Mitochondrial
      dysfunction seems to be more common in this group of myopathies than previously
      estimated, and may be of importance in the pathogenesis of these disorders.

PMID- 7732788
TI  - Peripheral nerve elongation by laser Doppler flowmetry controlled expansion:
      morphological aspects.
AB  - Peripheral nerve elongation by a tissue expander may offer an alternative to
      nerve grafting in the management of segmental nerve loss. We investigated the
      morphological changes in peripheral nerve following slow nerve elongation by
      laser Doppler flowmetry controlled expansion in a rabbit sciatic nerve model. The
      animals were randomly assigned to one of four groups, with an expander volume of
      0, 5, 10 or 15 cm3, respectively. An elongation of up to 40% was possible with
      preservation of clinical function. Nerve conduction velocity decreased in
      relation to elongation. Paranodal widening, followed by remyelination of the
      node, were early and constant morphological features. Demyelination and
      remyelination of whole internodes, and axonal degeneration occurred sporadically
      and did not correlate with elongation, rate of elongation or neurophysiological
      parameters. The model of laser Doppler flowmetry controlled nerve expansion
      provides a method for remodelling of myelin sheaths and lengthening of nerve
      fibers without axonal damage.

PMID- 7732789
TI  - Striatal cells containing the Ca(2+)-binding protein calretinin (protein 10) in
      ischemia-induced neuronal injury.
AB  - The present study concerns the vulnerability of striatal interneurons
      immunopositive for the Ca(2+)-binding protein calretinin to ischemic neuronal
      injury. An immunohistochemical study was carried out on the striata of rats which
      had undergone transient middle cerebral artery occlusion. Two weeks after the
      ischemia, there was a marked reduction in the number of calretinin-positive
      neurons in the ipsilateral ischemic lesion, although the striatal interneurons
      positive for parvalbumin, which are a neuronal population distinct from the
      calretinin-immunoreactive cells in the striatum, were spared in the insulted
      areas. The present data indicate that the striatal calretinin-positive neurons
      are less resistant to transient ischemia, suggesting that there may exist
      vulnerability differences among the striatal interneurons in ischemia-induced
      neuronal injury.

PMID- 7732790
TI  - The topographic distribution of brain atrophy in cortical Lewy body disease:
      comparison with Alzheimer's disease.
AB  - The topographic distribution of brain atrophy was quantified by image analysis of
      fixed coronal brain slices from four patients dying with cortical Lewy body
      disease (CLBD) all with Alzheimer-type pathology and compared to that in four
      other patients of similar age and gender dying with Alzheimer's disease (AD)
      alone. The pattern of atrophy in CLBD (+AD) was broadly similar to that in AD
      alone, suggesting that tissue loss was due mostly to parallel Alzheimer-type
      pathological changes and that the presence of Lewy bodies in cortical and
      subcortical neurons contributed little, if anything, to the overall degree of
      atrophy.

PMID- 7732791
TI  - Stress-response (heat-shock) protein 90 expression in tumors of the central
      nervous system: an immunohistochemical study.
AB  - This retrospective study deals with the expression of stress-response (heat
      shock) protein 90 (srp 90) in a series of 148 human brain tumors.
      Immunohistochemical procedures were employed; cells of the human breast cancer
      line MCF7 exposed to hyperosmolar stress served as positive controls. Deposits of
      reaction products were found in the cytoplasm and they displayed a granular
      pattern. srp 90 was detected in 14/31 meningiomas and 5/10 breast cancer
      metastases to the brain. The protein was also present in 6/13 glioblastomas and
      7/18 astrocytomas. In addition, a positive reaction was found in 2/10
      medulloblastomas, 2/14 primitive neuroectodermal tumors, 1/11 pituitary tumor,
      2/21 schwannomas and 2/11 lung tumor metastases; however, oligodendrogliomas and
      primary malignant lymphomas were not stained. The srp 90 was detected in Western
      blots of meningioma tissue homogenates. No significant immunohistochemical
      reaction was seen with sections of normal human cerebra, brain stem, cerebella,
      pituitary glands and spinal cords. These results document the expression of srp
      90 by a variety of primary and metastatic intracranial tumors.

PMID- 7732792
TI  - A long surviving case of amyotrophic lateral sclerosis with atrophy of the
      frontal lobe: a comparison with the Mitsuyama type.
AB  - A female patient with amyotrophic lateral sclerosis (ALS) showing psychiatric
      symptoms during her last 2 years of life is reported. Although pseudobulbar signs
      were seen at the onset of ALS and no respirator was used, the period from onset
      to death was rather long (9 years). The spinal lesions showed features common to
      ordinary ALS, while the marked atrophy with destructive changes throughout the
      frontal lobe seemed to be considerably more severe than that seen with either
      ordinary ALS or the Mitsuyama type of ALS. Since the clinical manifestations and
      histological characteristics are apparently different from those of the Mitsuyama
      type, our case may be a new nosological variant of ALS with psychiatric
      manifestations.

PMID- 7732793
TI  - Pleomorphic xanthoastrocytoma with a gangliomatous component: an
      immunohistochemical and ultrastructural study.
AB  - We report a case of a 24-year-old woman with left temporal pleomorphic
      xanthoastrocytoma (PXA) with atypical neuronal cells. Many neoplastic cells,
      otherwise typical of PXA, expressed glial fibrillary acidic protein, while
      neuronal cells with marked atypia were immunopositive for synaptophysin and
      neurofilament protein. This report supports a notion that PXA, like other
      astrocytic tumors, may have its gangliogliomatous counterpart.

PMID- 7732794
TI  - Vulvodynia--a complex syndrome of vulvar pain.
AB  - Vulvodynia is a syndrome of unexplained vulvar pain, sexual dysfunction, and
      psychological disability. The incidence of prevalence of this condition is not
      known. Several subtypes of vulvodynia have been recognized. Recognition of the
      distinct subsets of vulvodynia is a pre-requisite for successful management.
      Vulvar vestibulitis syndrome, cyclic vulvovaginitis, and dysesthetic vulvodynia
      are the most common subtypes. Other frequently misdiagnosed vulvar or vaginal
      conditions which can also cause culvodynia are vulvar papillomatosis, cytolytic
      vaginosis, lactobacillosis, and desquamative inflammatory vaginitis. In addition,
      many vulvar dermatoses can cause acute or chronic vulvar itching or pain, and are
      a frequent cause of differential diagnostic problems. In conclusion, vulvodynia
      is a complex multifactorial underdiagnosed clinical syndrome. Systematic
      epidemiologic, etiologic, and therapeutic studies of vulvodynia should be
      undertaken.

PMID- 7732795
TI  - Detection of fetal Y-specific DNA from the cervix.
AB  - Detection of fetal Y-specific DNA by polymerase chain reaction was performed on
      cervical samplings obtained from 24 patients who underwent first trimester
      suction termination of pregnancy. The results were compared with the fetal gender
      determined by Y-sequence polymerase chain reaction on the fetal parts. Fourteen
      male pregnancies were identified. Correct predictions were made in two (14.3%)
      from the cervical swabs and three (21.4%) from the trans-cervical samplings. The
      failure of isolation of fetal cells from the cervix was not related to the
      gestation of sampling.

PMID- 7732796
TI  - Variations in serum relaxin (hRLX-2) concentrations during human pregnancy.
AB  - STUDY OBJECTIVE: To study variations in serum relaxin concentrations during
      normal and abnormal human pregnancy and parturition and in umbilical cord blood.
      DESIGN AND PATIENTS: Diurnal variations were determined in samples collected
      every 2 hours for 24 hours (n = 4). Variations during pregnancy were studied in
      samples taken every 4th week from normal pregnant women (n = 26). Additionally
      samples were collected once a week from the 37th week of pregnancy and until
      spontaneously delivery (n = 5). Changes in relaxin during early pregnancy
      (gestational age: 30 to 97 days) were studied in serum from 12 normal pregnant
      women, 13 with spontaneous abortion and 38 with an ectopic pregnancy. Fetal serum
      was obtained at delivery from the umbilical vein (n = 20). All samples were
      analysed for relaxin by an ELISA based on human relaxin antibodies. MAIN RESULTS:
      No diurnal variation in relaxin concentrations were found. In normal pregnant
      women relaxin concentrations increased during the first 14 weeks of pregnancy.
      From week 14 to 24 a gradual decrease was found and the concentrations remained
      constant during the last part of pregnancy. No changes in concentrations were
      found immediately before or during spontaneous delivery. Women with abnormal
      pregnancies had lower serum relaxin values than normal early pregnant women. The
      relaxin concentration was significantly correlated to the serum HCG concentration
      in early pregnancy but not to the serum HPL levels after week 28. In the
      umbilical vein relaxin concentrations were low. CONCLUSION: The variation in
      circulating levels of relaxin during human pregnancy differs markedly from those
      found in other species. This suggests a different role for relaxin in human
      pregnancy.

PMID- 7732797
TI  - Perturbed (procoagulant) endothelium and deviations within the fibrinolytic
      system during the third trimester of normal pregnancy. A possible link to
      placental function.
AB  - PURPOSE: To evaluate the endothelial cell state and the possible relation to
      placental function in the third trimester of normal pregnancy by an indirect
      assessment of endothelial cell function. STUDY-DESIGN. Twenty-six pregnant women
      entered the study in the 30th week of pregnancy. Von Willebrand Factor, urate and
      key hemostatic variables were quantified at entry, and during the 33rd and 37th
      weeks of pregnancy. RESULTS: Levels of von Willebrand Factor, PAI-1 antigen, t-PA
      antigen; variables produced by the endothelial cell, increased during the third
      trimester of pregnancy. Serum urate, which is correlated with clinical outcome of
      pregnancy, increased during the study period and correlated directly with von
      Willebrand Factor and PAI-1 antigen, respectively. There was an inverse
      correlation between the concentrations of placenta-derived PAI-2 antigen and
      urate. CONCLUSIONS: In healthy human pregnancy the markers of endothelial related
      processes of coagulation and fibrinolysis pointed towards a procoagulatory state
      of the endothelial cell. However, the balance between fibrin formation and
      resolution seemed to be maintained in uncomplicated pregnancy. Our study
      indicated an association between this change of endothelial cell function and
      placental function.

PMID- 7732798
TI  - Oral poliovirus vaccination and pregnancy complications.
AB  - BACKGROUND: To determine whether the effect of live attenuated oral polio virus
      vaccine given to pregnant women increases pregnancy complications. METHODS: A
      study of women who had been vaccinated against poliovirus during a national
      vaccination campaign and who had delivered by cesarean section in three
      obstetrical hospitals in southern Finland. One thousand seven hundred and forty
      seven vaccinated women (in three study cohorts), and their 2293 nonvaccinated
      controls (in two reference cohorts) were analyzed. Subjects are out of 22,000
      deliveries evaluated earlier. RESULTS: Vaccinated sectioned women did not show an
      excess of pregnancy complications. The mean rate of cesarean sections was 18.4%
      in the study cohorts and 18.9% in the reference cohorts counted from the 22,000
      deliveries. CONCLUSIONS: Oral live attenuated polio virus vaccine does not
      increase pregnancy complications and is considered a safe alternative for
      vaccinating pregnant women.

PMID- 7732799
TI  - Preventing the recurrence of atonic postpartum hemorrhage: a double-blind trial.
AB  - BACKGROUND: We conducted a double-blind randomized controlled trial to compare a
      conventional regimen of oxytocin and ergometrine with administration of the
      prostaglandin E2 analogue, sulprostone, for prophylaxis of postpartum hemorrhage
      in high-risk women. METHODS: Women with a history of postpartum hemorrhage > or =
      1000 were assigned to two coded prophylactic regimens. Drugs, given respectively
      at delivery of the anterior shoulder and after delivery of the placenta, were
      oxytocin and ergometrine in the control group, and sulprostone and placebo in the
      experimental group. Eighty-one women, 69 of whom actually participated in the
      trial, were investigated. Both the women and the caregivers were unaware of
      treatment allocation. RESULTS: Although the trial was terminated prematurely
      there was a slight, but not statistically significant, preference for the
      sulprostone regimen in terms of blood loss and use of blood transfusion. No
      serious adverse effects were noted with either of the two regimens. CONCLUSION:
      Prostaglandins may be more effective for preventing recurrence of severe
      postpartum hemorrhage than the oxytocin and ergometrine combination, but they do
      not eliminate the risk entirely.

PMID- 7732800
TI  - Background factors and scoring systems in relation to pregnancy outcome after
      fertility surgery.
AB  - BACKGROUND: A study was initiated to identify background factors, clinical
      features and pre-operative scoring systems of importance for future selection of
      patients suitable for fertility surgery. METHODS: Surgical procedures, background
      factors and scoring systems for tubal lesions and adnexal adhesions and risk
      factors for ectopic pregnancy were analyzed with respect to possible correlation
      to subsequent fertility in a retrospective study of 246 patients undergoing
      fertility surgery (adhesiolysis, salpingostomy, tubal anastomoses, implantation
      and myomectomy) between 1986 and 1990. Follow-up periods varied between one to
      six years. RESULTS: In 94% of cases a second look laparoscopy was performed.
      Adhesiolysis was done in 62%. The conception rate was 41.1%, the ectopic
      pregnancy rate was 14.6% and the delivery rate was 22.0%. Myomectomy procedures
      were most successful, with a delivery rate of 44.0% and no ectopic pregnancy.
      Previous ectopic pregnancy indicated a higher risk for recurrence, as did a high
      risk score for ectopic pregnancy. The extent of tubal damage was most relevant to
      subsequent fertility. Salpingostomies in women with mild or moderate tubal damage
      resulted in a delivery rate of 25.4% compared with those with severe damage
      (5.6%). No deliveries were seen after lysis of extensive adnexal adhesions.
      CONCLUSION: Adhesion formation is not negligible and a second look laparoscopy is
      recommended. Women with fibroids should always be considered for fertility
      surgery, not only because of high success rates, but also as an adjuvant to
      subsequent in vitro fertilization. Patients with previous ectopic pregnancy,
      extensive adhesions and unfavorable tubal scores should not be considered for
      surgery but referred for in vitro fertilization.

PMID- 7732801
TI  - An oocyte donation program with goserelin down-regulation of voluntary donors.
AB  - BACKGROUND: In ovum donation programs oocytes can be requested from infertile
      women going through an in vitro fertilization cycle. Currently, when embryos can
      be cryopreserved, these donors have virtually disappeared. Instead, most donors
      have been healthy fertile volunteers willing to go through an IVF attempt solely
      for the purpose of donating all oocytes. METHODS: Sixty-four patients had 93
      started cycles of oocyte donation from 59 donors. Twenty recipients had primary
      ovarian failure, 24 had secondary ovarian failure, 15 had had repeated failures
      in earlier IVF attempts and five were carriers of genetic diseases. The donors
      were 51 healthy volunteers recruited through the press. Eight patients from an
      IVF program donated excess oocytes. Donors were not paid and their mean age was
      30 years. To minimize discomfort of the treatment, a long-acting GnRH-agonist,
      goserelin, was used for down-regulation. RESULTS: The pregnancy rate per transfer
      with fresh embryos was 28.4% (23/81) and with frozen-thawed embryos, 17% (3/18).
      Twenty-one healthy infants have been born including one set of triplets and three
      sets of twins. Nine pregnancies ended in abortion and one in intrauterine fetal
      death. The most common complications of pregnancy were pre-eclampsia and
      pregnancy-induced hypertension (41.2%, 7/17). Ten of 17 patients delivered by
      cesarean section (58.8%). CONCLUSION: It was possible, through the press, to
      obtain highly motivated oocyte donors, who go through IVF treatment solely for
      altruistic reasons. Oocyte recipients appear to have many complications in their
      pregnancies. Until more data are available, these patients need a high standard
      of obstetric care.

PMID- 7732802
TI  - Transvaginal sonography in the management of ectopic pregnancy.
AB  - During a 3-year period, 525 women referred to our department with abdominal pain
      and/or vaginal bleeding in the first trimester of pregnancy were evaluated by
      transvaginal sonography. Ectopic pregnancy was suspected and laparoscopy done
      when sonography showed an empty uterus or pseudosac together with free pelvic
      fluid and/or a tubal mass. Fifty-seven patients fulfilled these criteriae. Among
      these patients, sonography showed an empty uterus in 48, pseudosac in five, a non
      diagnostic intrauterine echo in four, a tubal mass in 45 and free pelvic fluid in
      54. Laparoscopy confirmed ectopic pregnancy in 53 patients (93.0%). There were
      only five tubal ruptures. Pelvic blood was found in all of the 54 patients with
      free fluid on sonography; i.e. in 51 of 53 patients with ectopic pregnancy and in
      three with miscarriage. Forty-nine patients with ectopic pregnancy were managed
      by laparoscopy and four by laparotomy. All were hemodynamically stable. The
      diagnostic sensitivity and specificity of vaginal sonography for ectopic
      pregnancy was 96.2% and 99.4%, respectively, for the finding of free pelvic
      fluid, and 81.1% and 99.6% for a tubal mass. All patients with ectopic pregnancy
      were correctly selected for laparoscopic management. Transvaginal sonography is a
      valuable tool in the early diagnosis of ectopic pregnancy.

PMID- 7732803
TI  - The association between hormone levels and vascular resistance in uterine and
      ovarian arteries in spontaneous menstrual cycles--a Doppler ultrasound study.
AB  - Ninety-four infertility patients were studied by Doppler ultrasound during
      spontaneous ovulatory menstrual cycles. The pulsatility index (PI) in uterine and
      ovarian arteries was measured in the follicular and midluteal phase of the cycle.
      Associations between high PI values and hormones (estradiol, progesterone,
      prolactin, testosterone, follicle stimulating hormone) measured during the
      investigated cycle and age were evaluated. A high PI in uterine arteries in the
      follicular phase was associated with low estradiol (E2) and progesterone (P)
      levels in the studied cycle. In the luteal phase PI values of uterine arteries
      have no obvious association with E and P levels, and other vasoactive compounds
      influence the perfusion of uterus during this period. The other hormones analysed
      and age did not correlate with vascular resistance in spontaneous ovulatory
      cycles.

PMID- 7732805
TI  - Small bowel herniation after laparoscopically assisted vaginal hysterectomy.
AB  - Laparoscopically assisted vaginal hysterectomies have been done with increasing
      frequency in the United States. To date, minimal complications have been noted
      with this procedure. The authors review a series of 90 individuals and note a
      three percent small bowel obstruction rate. This complication is more common in
      this group of patients than in patients having a standard abdominal hysterectomy.
      Since this operation has been commonly performed, it is often possible to convert
      an abdominal hysterectomy to a vaginal approach, this increase in complications
      is exceedingly high. The authors recommend closure of lateral abdominal wall port
      sites under direct laparoscopic visualization to prevent this serious
      complication.

PMID- 7732804
TI  - The influence of social class on parity and psychological reactions in women
      coming for induced abortion.
AB  - OBJECTIVE: To test the hypothesis that the correlation between legal abortion and
      socio-economic conditions, known from the time when abortion was restricted, has
      current validity. To evaluate the effect of social class on network support and
      psychological reactions. DESIGN: Consecutive sampling and semistructured personal
      interviewing. SUBJECTS: 444 women living in the city of Gothenburg and applying
      for legal termination of pregnancy in the first trimester. SETTING: The
      department of gynaecology at a university hospital with primary care
      responsibility for legal abortions. RESULTS: The 667 health administration
      districts of Gothenburg were ranked into four groups according to the mean
      income. Women living in lower socio-economic districts were younger. Irrespective
      of age, previous experience of induced abortion was more common among them (p <
      0.001). Unsatisfactory network response or support was common (37%), but equally
      shared between the social classes. Discontinuation of oral contraception during
      the previous six months was twice as common among teenagers (40.0%) as among
      other women (p < 0.001) but without social differences. Pitman's permutation test
      was used for statistical analyses. CONCLUSION: Socio-economic conditions have a
      strong and inverse correlation to previous experience of induced abortion.
      Psychological reactions and needs did not vary with class.

PMID- 7732806
TI  - In vitro production of cyclic AMP and steroids from an ovarian Sertoli-Leydig
      cell tumor. Notes on clinical management.
AB  - A 27 year old nulliparous woman with a history of chronic anovulation and signs
      of virilization with a markedly elevated serum level of testosterone, underwent a
      laparotomy with peroperative bilateral ovarian vein catheterization and bilateral
      bisection of both ovaries. A solid, 1.5 cm, well delimited tumor located
      centrally in the right ovary, was excised. Testosterone levels in ovarian venous
      blood from the tumor bearing side, were 88.4 nmol/l and from the contralateral
      ovary 3.9 nmol/l. Histopathological examination showed a Sertoli-Leydig cell
      tumor which was radically extirpated. Postoperatively, the serum levels of
      androgen normalized, the woman had regular cycles, became pregnant and delivered
      a normal female baby. Pieces of tumor tissue were incubated for 2 h, with and
      without addition of gonadotropins and adrenocorticotropic hormone (ACTH). Human
      chorionic gonadotropin (CG), follicle stimulating hormone (FSH) and
      adrenocorticotropic hormone (ACTH) caused significant increases in cyclic
      monophosphate (cAMP) production in tumor tissue in vitro, as compared to
      controls. Furthermore, ACTH also significantly stimulated 17 beta-estradiol
      production. In tumor cells cultured for 48 h, FSH slightly, but not
      significantly, increased the production of progesterone. In the cell culture,
      [3H]-thymidine incorporation into deoxyribonucleic acid (DNA) was stimulated by
      IGF1 alpha but not by hCG and FSH. It is concluded that Sertoli-Leydig cell
      tumors may be sensitive to gonadotropins and ACTH and that their small size,
      solid shape and intra-ovarian localization can cause diagnostic difficulties.

PMID- 7732807
TI  - Varicella pneumonia complicating pregnancy.
AB  - Varicella pneumonia can endanger the life of pregnant women. We have a case of
      varicella pneumonia complicating pregnancy in the third trimester. The patient
      required intubation, early treatment with acyclovir (700 mg/IV every eight
      hours), as well as the extraction of the fetus by cesarean section before the
      time gestation was completed. Early treatment with acyclovir has improved hope
      for these patients.

PMID- 7732808
TI  - Prenatal diagnosis of osteogenesis imperfecta.
AB  - The lethal perinatal types (II A-C) of osteogenesis imperfecta are reported to
      occur in approximately 1:55000 births. We here present three cases in three
      unrelated families, diagnosed by antenatal ultrasound within one year. A reliable
      diagnosis of the lethal perinatal type of osteogenesis imperfecta can be made by
      ultrasound examination during the second trimester, by identification of
      fractures of the long bones. The compression of the fetal head by the ultrasound
      probe and the low echogeneity of the cranium, should raise the suspicion of
      skeletal dysplasia, but is not diagnostic for osteogenesis imperfecta. The
      diagnosis is confirmed by postmortem examination including radiography and
      biochemical studies of cultivated fibroblasts from the fetus. Although rare, this
      lethal condition should be recognized when an ultrasound examination is
      performed, to prevent unnecessary obstetric intervention. In families with a
      previously affected fetus, prenatal diagnosis by first trimester transvaginal
      ultrasound investigation or chorionic villus sampling should be discussed.

PMID- 7732809
TI  - 9th International Conference on Prostaglandins and Related Compounds. Florence,
      Italy, June 6-10, 1994.

PMID- 7732810
TI  - 5-lipoxygenase: structure and stability of recombinant enzyme, regulation in Mono
      Mac 6 cells.

PMID- 7732811
TI  - Characterization of human prostaglandin H synthase genes.

PMID- 7732812
TI  - Structure and expression of the human prostaglandin endoperoxide synthase 2 gene.

PMID- 7732813
TI  - Lipoxygenase structure and mechanism.

PMID- 7732814
TI  - Evaluation of prostaglandin H synthase-1 membrane topology and endoplasmic
      reticulum retention signals.

PMID- 7732815
TI  - Endothelin regulates PGE2 formation in rat mesangial cells through induction of
      prostaglandin endoperoxide synthase-2.
AB  - Endothelin-1 stimulates vascular smooth muscle and mesangial cells to release
      prostaglandin E2 which attenuates the vasoconstrictor and mitogenic effects of
      endothelin. The role of endothelin-1 to regulate prostaglandin endoperoxide
      synthase (PGHS)-1 and -2 gene expression and protein synthesis was evaluated in
      cultured mesangial cells. Endothelin induced mRNA and protein expression for PGHS
      2 but not for PGHS-1. A direct correlation was observed between the mass of
      immunoprecipitated PGHS protein and PGE2 synthetic enzymatic activity.

PMID- 7732816
TI  - Molecular cloning and expression of prostacyclin synthase from endothelial cells.

PMID- 7732817
TI  - Characterization of the cyclooxygenase activity of human blood prostaglandin
      endoperoxide synthases.

PMID- 7732818
TI  - Human genes for prostaglandin endoperoxide synthase-2, thromboxane synthase and
      prostacyclin synthase.

PMID- 7732819
TI  - Genomic organization and regulation of the human thromboxane synthase gene.

PMID- 7732820
TI  - 11-hydroxythromboxane B2 dehydrogenase from porcine kidney is identical to
      cytosolic aldehyde dehydrogenase.

PMID- 7732821
TI  - Leukotriene-deficient mice generated by targeted disruption of the 5-lipoxygenase
      gene.

PMID- 7732822
TI  - Localization of 5-lipoxygenase to the nucleus of resting rat basophilic leukemia
      cells.

PMID- 7732823
TI  - Properties of LTA4 synthase in human neutrophil preparations.

PMID- 7732824
TI  - On the interfacial phenomena in lipoxygenase catalysis.

PMID- 7732825
TI  - Oxygenation of arachidonylethanolamide (anandamide) by lipoxygenases.

PMID- 7732826
TI  - Molecular cloning and expression of human leukotriene C4 synthase.

PMID- 7732827
TI  - Structures, properties and distributions of prostanoid receptors.

PMID- 7732828
TI  - Characterization of human LTC4 synthase.

PMID- 7732829
TI  - Human umbilical vein endothelial cells contain leukotriene A4 hydrolase which is
      regulated by phosphorylation.

PMID- 7732830
TI  - Metal inhibition of LTA4 hydrolase and cellular 5-lipoxygenase activity.

PMID- 7732831
TI  - Enzymatic formation of hepoxilin A3.

PMID- 7732832
TI  - Pieces in the puzzle: novel arachidonate metabolites.

PMID- 7732833
TI  - Biosynthesis and degradation of alpha-paranaric acid and related conjugated
      tetraene fatty acids.

PMID- 7732834
TI  - Identification of arachidonate epoxides in human platelets.

PMID- 7732835
TI  - Arachidonic acid omega-hydroxylation and cytochrome P450 4A expression in the rat
      kidney.

PMID- 7732836
TI  - Amiloride-sensitive ion transport inhibition by epoxyeicosatrienoic acids in
      renal epithelial cells.

PMID- 7732837
TI  - Epoxyeicosatrienoic acids stimulate the growth of vascular smooth muscle cells.

PMID- 7732838
TI  - The isoprostanes: novel markers of lipid peroxidation and potential mediators of
      oxidant injury.

PMID- 7732839
TI  - Formation of F2-isoprostanes during the oxidation of human low density
      lipoprotein by peroxynitrite.

PMID- 7732840
TI  - Cyclooxygenase dependent formation of 8-iso-prostaglandin F2 alpha by human
      platelets.

PMID- 7732841
TI  - The regulation and role of TIS10 prostaglandin synthase-2.

PMID- 7732842
TI  - Physiological formation of 8-epi-PGF2 alpha in vivo is not affected by
      cyclooxygenase inhibition.

PMID- 7732843
TI  - Molecular and functional evidence for the distinct nature of F2-isoprostane
      receptors from those of thromboxane A2.

PMID- 7732844
TI  - EP4-receptors and cyclic AMP in pig venous smooth muscle: evidence with agonists
      and the EP4-antagonist, AH22921.

PMID- 7732845
TI  - Regulated expression of the gene coding for the human thromboxane A2 receptor.

PMID- 7732846
TI  - Androgen regulation of thromboxane A2 receptors.

PMID- 7732847
TI  - Signal transductions of three isoforms of mouse prostaglandin E receptor EP3
      subtype.

PMID- 7732848
TI  - Molecular cloning and expression of a cDNA of the bovine prostaglandin F2 alpha
      receptor.

PMID- 7732849
TI  - Prostacyclin effects on adenylate cyclase in platelets and vascular smooth
      muscle: interaction with an inhibitory receptor or partial agonism?

PMID- 7732850
TI  - Receptors for cys-leukotrienes in human lung parenchyma: characterization by
      computer modelling and photoaffinity labelling of binding sites.

PMID- 7732851
TI  - Synergism exhibited by LTD4 and PAF receptor antagonists in decreasing antigen
      induced airway microvascular leakage.

PMID- 7732852
TI  - SB 209247, a high affinity LTB4 receptor antagonist demonstrating potent
      antiinflammatory activity.

PMID- 7732853
TI  - Estimation of antagonistic activity of ONO-4057 against leukotriene B4 in humans.

PMID- 7732854
TI  - Prostanoid and leukotriene receptors: a progress report from the IUPHAR working
      parties on classification and nomenclature.

PMID- 7732855
TI  - Cytokines and eicosanoids regulate PAF receptor gene expression.

PMID- 7732856
TI  - The orientation of prostaglandin endoperoxide synthase-1 in the endoplasmic
      reticulum of transiently transfected cos-1 cells.

PMID- 7732857
TI  - The 5-lipoxygenase pathway in normal and malignant human B lymphocytes.

PMID- 7732858
TI  - Characterization of prostaglandin E2 receptors on normal and malignant B
      lymphocytes.

PMID- 7732859
TI  - Production of PGE2 and 15-HETE by fibrosarcoma cells.

PMID- 7732860
TI  - Evidence for reciprocal regulation of pro- and anti-inflammatory lymphokines in
      rat nephrotoxic serum (NTS) nephritis.

PMID- 7732861
TI  - Crosstalk in signal transduction via EP receptors: prostaglandin E1 inhibits
      chemoattractant-induced mitogen-activated protein kinase activity in human
      neutrophils.

PMID- 7732862
TI  - Inducible prostaglandin synthase in cell injury.

PMID- 7732863
TI  - Novel mode of monocyte 5-lipoxygenase stimulation.

PMID- 7732864
TI  - 5-lipoxygenase expression in cultured human keratinocytes.

PMID- 7732865
TI  - Regulation of leukotriene C4 synthase in human platelets via receptor-mediated
      mechanisms.

PMID- 7732866
TI  - Synergistic prevention of endotoxin induced mortality in rats by PGE1 and
      particles.

PMID- 7732867
TI  - Induction of prostaglandin H synthase-2 in rat carrageenin-induced pleurisy and
      effect of a selective COX-2 inhibitor.

PMID- 7732868
TI  - Cyclooxygenase in rat pleural hypersensitivity reactions.

PMID- 7732869
TI  - Expression cloning of human LTC4 synthase.

PMID- 7732870
TI  - Leukotrienes and other mediators of the Schultz-Dale reaction in guinea-pig lung
      parenchyma.

PMID- 7732871
TI  - Arachidonic acid liberation from rat tracheal epithelial cells by alveolar
      macrophages.

PMID- 7732872
TI  - Airway hyperresponsiveness induced by 13-hydroxyoctadecadienoic acid (13-HODE) is
      mediated by sensory neuropeptides.

PMID- 7732873
TI  - Furosemide attenuates bronchial responsiveness to antigen challenge "in vitro".

PMID- 7732874
TI  - Thromboxane biosynthesis and pulmonary function in cystic fibrosis.

PMID- 7732875
TI  - Lupus anticoagulant IgGs do not depend on serum for the induction of
      cyclooxygenase-2 by human endothelial cells.

PMID- 7732876
TI  - Restoration of prostacyclin synthesis by transfer of prostaglandin H synthase
      cDNA.

PMID- 7732877
TI  - Expression of 15-lipoxygenase in transplant coronary artery disease.

PMID- 7732878
TI  - Blood cell-vascular wall interactions and the production of coronary contracting
      sulfidopeptide leukotrienes in isolated, cell- perfused, rabbit heart.

PMID- 7732879
TI  - Urinary thromboxane has diagnostic value in myocardial infarction.

PMID- 7732880
TI  - Serum lipids and fatty acids in populations on a lake-fish diet or on a
      vegetarian diet, in Tanzania.

PMID- 7732881
TI  - Inhibition of cyclooxygenase activity in human endothelial cells by homocysteine.

PMID- 7732882
TI  - ONO-AP-500-02: a non prostanoid prostaglandin I2 mimetic with inhibitory activity
      against thromboxane synthase.

PMID- 7732883
TI  - A double-blind, multi-center, dose comparison study of TTC-909 for the treatment
      of peripheral vascular disorders.

PMID- 7732884
TI  - Influence of prostaglandin E1 on in vitro oxidation of human low density
      lipoproteins.

PMID- 7732885
TI  - Principles of thromboregulation: control of platelet reactivity in vascular
      disease.

PMID- 7732886
TI  - Mechanisms for lipoxin A4 induced neutrophil dependent cytotoxicity for human
      endothelial cells.

PMID- 7732887
TI  - Regulation of 12-lipoxygenase by platelet-derived growth factor in vascular
      smooth muscle cells.

PMID- 7732888
TI  - Biological properties of 12(S)-HETE in cancer metastasis.

PMID- 7732889
TI  - Involvement of cyclooxygenase-2 in bone loss induced by interleukin-1 beta.

PMID- 7732890
TI  - Transforming growth factor-beta and 1,25-dihydroxyvitamin D3 induce 5
      lipoxygenase activity during myeloid cell maturation.

PMID- 7732891
TI  - Effect of PGE2 on c-Myc and Bcl-2 production and programmed cell death in human
      lymphocytes.

PMID- 7732892
TI  - Regulation and signal transduction of PAF receptor.

PMID- 7732893
TI  - Platelet activating factor induces transformation of human fibroblasts.

PMID- 7732894
TI  - Evidence for the predominant role of intracellular PAF binding sites in the
      regulation of phospholipase A2 in human neutrophils.

PMID- 7732895
TI  - ABT-299, a potent antagonist of platelet activating factor.

PMID- 7732896
TI  - Discovery of a better aspirin.

PMID- 7732897
TI  - Human prostanoid receptors: cloning and characterization.

PMID- 7732898
TI  - Interactions between prostaglandins, muscarinic agonists and the adenylate
      cyclase and phospholipase C systems in dog ciliary smooth muscle.

PMID- 7732899
TI  - Preclinical pharmacology of latanoprost, a phenyl-substituted PGF2 alpha
      analogue.

PMID- 7732900
TI  - Mechanism of the prostaglandin-induced reduction of intraocular pressure in
      humans.

PMID- 7732901
TI  - Comparative phase III clinical trial of latanoprost and timolol in patients with
      elevated intraocular pressure.

PMID- 7732902
TI  - Erectile dysfunction--vasomotor actions of PGE1, its metabolites and other
      prostaglandins.

PMID- 7732903
TI  - The rationale for prostaglandin E1 (alpha-alprostadil) in the management of male
      impotence.

PMID- 7732904
TI  - Physiopathology of the erectile dysfunction.

PMID- 7732905
TI  - The combined use of prostaglandin and antiprogestin in human fertility control.

PMID- 7732906
TI  - Prostaglandins as ocular hypotensive agents; development of an analogue for
      glaucoma treatment.

PMID- 7732907
TI  - Leukotriene antagonists and inhibitors: clinical applications.

PMID- 7732908
TI  - Multiple forms of phospholipase A2 in macrophages capable of arachidonic acid
      release for eicosanoid biosynthesis.

PMID- 7732909
TI  - AA-release is under control of PLA2 and DAG lipase in rat liver macrophages.

PMID- 7732910
TI  - Structural characterization of pancreatic group I phospholipase A2 receptor.

PMID- 7732911
TI  - Inhibition of CoA-independent transacylase reduces inflammatory lipid mediators.

PMID- 7732912
TI  - The 3.1 A X-ray crystal structure of the integral membrane enzyme prostaglandin
      H2 synthase-1.

PMID- 7732913
TI  - [Recent advance of macular surgery].

PMID- 7732914
TI  - [Retinochoroidal circulatory disturbances and blood component abnormalities].
AB  - The recent analysis of blood components has revealed that retinochoroidal
      circulation may be disturbed in patients with abnormalities of blood components.
      These blood abnormalities include iron deficiency anemia with or without
      thrombocytosis, dysplasminogenia, von Willebrand's disease, protein S deficiency,
      protein C deficiency, and abnormal platelet function. The ophthalmoscopic
      findings in these disorders include retinal vein occlusion, retinal artery
      occlusion, choroidal circulatory disturbance, and vitreoretinal hemorrhage. The
      incidence of blood component abnormalities is high in young patients who rarely
      have systemic hypertension or arterial sclerosis. We review these blood disorders
      and emphasize the importance of blood analysis in the patients with
      retinochoroidal circulatory disturbances.

PMID- 7732915
TI  - [Pharmacokinetics of subconjunctivally injected drugs in the anterior segment of
      rabbit eyes].
AB  - We injected 12.5, 25, 50 and 100 microliters portions of a combined solution of
      2.5% sodium fluorescein (FL), 2.5% cefmenoxim hemihydrochloride (CMX), and 0. 25%
      chloramphenicol (CP) subconjunctivally into rabbit eyes by various methods. Drug
      levels were monitored in the tears and aqueous humor and measured via high
      performance liquid chromatography. In the tear fluid, the concentrations of CP
      decreased more rapidly with time than FL and CMX. The drugs penetrated the
      rabbit's eyes better when injected subconjunctivally than when administered by
      sub-Tenon's injection. After subconjunctival injection through the eyelid, the
      drug concentration in the tears decreased with time in almost the same way as for
      injection through the conjunctival membrane. There was little difference between
      the presence and absence of a puncture hole in the conjunctiva. When the whole
      cornea was sealed with cyanoacrylate glue to block transcorneal absorption, the
      FL concentration in the aqueous humor was 30% of that in the control and the CP
      concentration was less than 10% of that in the control. About 70% of FL
      penetrating the eyes was derived from the transcorneal route but most of the CP
      was derived from the transcorneal route. FL in 1% or 0. 25% sodium hyarulonate
      (HA) and saline was injected subconjunctivally, and the concentrations of FL in
      the cornea and vitreous humor were measured. FL in 0.25% HA penetrated rabbit
      eyes better than that in 1% HA. These findings suggest that by dissolving the
      drug in an adequate concentration of HA solution, better penetration of drugs
      into the eye can be obtained.

PMID- 7732916
TI  - [The effect of an endothelin receptor antagonist, 97-139, on intraocular pressure
      in rabbits].
AB  - We studied intraocular pressure (IOP) response to an intravitreal injection of
      10(-5)M (20 microliters) endothelin-1 (ET-1) in unanesthetized rabbits, and found
      a transient IOP rise followed by a prolonged IOP reduction. ET-1 (10(-6)M) caused
      a sustained IOP reduction without an initial IOP rise. The ETA receptor selective
      antagonist, 97-139 (10(-2)M, 20 microliters), had no effect when used alone;
      however, when used in combination with ET-1 (10(-5)M), 97-139 (10(-2)M)
      significantly blocked the ocular hypotensive response to ET-1. 97-139 (10(-3)M),
      when used with 10(-6)M ET-1, also suppressed the IOP reduction induced by ET-1.
      Aqueous prostaglandin (PG) E2, determined by radioimmunoassay, was significantly
      elevated following intravitreal injection of ET-1 (10(-5)M). Prior injection of
      97-139 (10(-2)M) significantly suppressed the elevation of aqueous PGE2
      concentration caused by ET-1 (10(-5)M). These results suggest that both the IOP
      response and the elevation of aqueous PGE2 following ET-1 injection are at least
      partially mediated by ETA receptor.

PMID- 7732917
TI  - [Histopathological studies on the rds mouse retina--relationship between
      photoreceptor and pigment epithelial cells].
AB  - We used light and electron microscopy to examine detailed ultrastructural changes
      in the course of the development and degeneration of the rds mouse (rds/rds)
      retina with particular reference to the relationship between the photoreceptor
      and retinal pigment epithelial cells. During the first 6 postpartum days, the
      mutant retina showed the same developmental pattern as in normal mice. After
      that, however, rds mouse retinas failed to develop the photoreceptor outer
      segments. After 14 days, the photoreceptor inner segments and the cilia were all
      arranged parallel in the same direction in which the pigment epithelial cells
      extend their long microvilli. The inner segments and the cilia were very long and
      surrounded by the microvilli of the retinal pigment epithelial cells in the
      mutant retinas 21 days postpartum or latter. Some inner segments and cilia showed
      cytoplasmic degeneration in the part surrounded by the microvilli, while the
      other part appeared normal. There were pigment epithelial cells that contained
      fragments of the inner segments. The photoreceptor nucleus and inner segment were
      reduced in number after 21 days. These findings indicate that the pigment
      epithelial cells play a role in photoreceptor degeneration in rds mice.

PMID- 7732918
TI  - [Binding of amaranthin in human retina].
AB  - The binding of amaranthin, specific for Gal beta 1,3 GalNAc and sialic acid Gal
      beta 1,3 GalNAc sequences, to the human retina was investigated with avidin
      biotinylated peroxidase. Amaranthin bound to the cone and rod photoreceptors,
      inner plexiform layer, ganglion cells, and nerve fibers. Since peanut agglutinin,
      specific for Gal beta 1,3 GalNAc, selectively binds to cones, we conclude that O
      glycoside-linked glycoconjugates are present on the surfaces of both cones and
      rods: Gal beta 1,3 GalNAc and sialic acid Gal beta 1,3 GalNAc are terminal sugars
      of the glycoconjugates around cones and rods, respectively.

PMID- 7732919
TI  - [A statistical study of ocular complications of herpes zoster ophthalmicus and
      its prolongation factors].
AB  - A statistical study was carried out on 218 patients (107 male and 111 female)
      with herpes zoster ophthalmicus (HZO) who visited our clinic from April 1985 to
      March 1992. The incidence of ocular complications (OCs) and the rate of prolonged
      OCs (over 6 months) were also studied with the factors that were considered to
      have affected them. There were 114 patients who showed OCs out of 218 HZO
      patients (52.3%). The incidence of OCs was higher among the patients with nose
      eruption than among those without (p < 0.001), and lower among the patients with
      acyclovir treatment in advance than among those without (p < 0.001). The rate of
      prolonged OCs was higher among the patients over 50 years old than among those
      under 50 years old (p < 0.05), higher among the patients with nose eruption than
      among those without (p < 0.05), and lower among the patients with acyclovir
      treatment in advance than among those without (p < 0.01). Those with nose
      eruption had a high rate of prolonged iritis. Severe visual acuity loss remained
      in 3 cases (2.6%): 2 cases of corneal opacity in the center and 1 case of
      neurouveitis. Two patients suffered from high intraocular pressure complicated
      with prolonged iritis.

PMID- 7732920
TI  - [Quantitative evaluation of corneal irregular astigmatism using computed corneal
      topography].
AB  - A new method was developed to quantify corneal irregular astigmatism using
      computed corneal topography. Refractive powers on a mire ring projected on a
      toric plane (regular cornea) can be approximated to follow a sine curve. The
      discrepancy between the approximated sine curve and actual refractive powers was
      calculated and employed as a parameter of corneal irregular astigmatism.
      Artificial precision models of a sphere and a toric plane showed similar
      parameters and the least amount of irregular astigmatism (0.02-0.05D).
      Consecutive measurements on normal human corneas displayed a reproducible
      irregular astigmatism range of 0.10-0.25D. Irregular astigatism of the eyes with
      pterygium was significantly greater than that of normal human controls even from
      early stages of the disease. Surgery for removal of the pterygium normalized the
      amount of regular astigmatism regardless of the size of the pterygium, but
      irregular astigmatism of the eyes with large pterygium (the apex reaching within
      the central 2 mm cornea) remained at a significantly higher than normal level. It
      was concluded that the current method enables a quantitative analysis of corneal
      irregular astigmatism, independent by the amount of regular antigmatism.

PMID- 7732921
TI  - [Quantitative analyses of glycosaminoglycans in tear fluids in normal human eyes
      and eyes with corneal epithelial disorders].
AB  - The existence and pathophysiological role of glycosaminoglycans in the tear fluid
      in humans was investigated using quantitative analyses of hyaluronic acid and
      chondroitin sulfate in the tear fluid. The subjects were 42 eyes of 31 normal
      controls, 9 eyes of 9 patients with superficial punctate keratitis (SPK), and 13
      eyes of 13 patients with epithelial defect. After an instillation of 100
      microliters saline solution in the conjunctival sac, as much tear fluid as
      possible was collected from the lower cul-de-sac. The glycosaminoglycans in the
      tears were then treated with chondroitinase ABC to make fractions of unsaturated
      disaccharides. The quantities of disaccharides were determined by high
      performance liquid chromatography. Concentrations were expressed as nanomoles of
      unsaturated disaccharides per protein in the tears. The concentrations of
      hyaluronic acid and chondroitin sulfate in the normal controls were 0.07 +/-
      0.12(n mol/mg protein) and 6.91 +/- 3.63 (n mol/mg protein), respectively. The
      mean concentration of hyaluronic acid was significantly higher in patients with
      epithelial erosion than in normal controls, whereas the mean concentration of
      chondroitin sulfate was significantly lower in patients with epithelial erosion
      than in normal controls. There was no significant difference in the concentration
      of glycosaminoglycans between the patients with SPK and normal controls. The
      results of our study suggest that glycosaminoglycans are synthesized and
      endogenously secreted into the tear fluids and, especially in the case of
      hyaluronic acid, may play an important role in corneal epithelial wound healing
      in patients with epithelial erosion.

PMID- 7732922
TI  - [Corneal autofluorescence in patients with diabetic retinopathy].
AB  - Corneal autofluorescence was investigated by fluorophotometry in patients with
      non-insulin-dependent diabetes mellitus and healthy volunteers, and evaluated as
      to its correlation with diabetic retinopathy. The corneal autofluorescence of
      diabetes patients, which was significantly higher than that of healthy controls,
      correlated significantly with the severity of retinopathy. In addition, the
      corneal autofluorescence of burned-out retinopathy patients was significantly
      lower than that of proliferative retinopathy patients. These results suggest that
      corneal autofluorescence is correlated with retinal ischemia and that corneal
      autofluorescence can be an indicator of the activity of diabetic retinopathy.
      Corneal autofluorescence may originate in the accumulation of some factor induced
      by retinal ischemia within the corneal stroma.

PMID- 7732923
TI  - [Hypotonous maculopathy following trabeculectomy with mitomycin C].
AB  - We retrospectively studied incidence, prognosis and predictive factors of
      hypotonous maculopathy following trabeculectomy with adjunctive mitomycin C. The
      subjects were 208 cases (208 eyes) with various types of glaucoma with clear
      media, who were followed up for at least three months postoperatively. The follow
      up periods ranged from 3 to 44 months with a mean of 21.1 months. The incidence
      of the maculopahy was 9.1% (19/208). The postoperative intraocular pressures
      (IOPs) varied between 1 and 6 mmHg in the presence of maculopathy. The
      maculopathy disappeared in 14 eyes (74%) spontaneously or following ocular
      hypertensive therapy including application of trichloracetic acid and
      subconjunctival injection of autologous blood. The final visual acuity
      deteriorated two lines or more in 8 eyes (42%). A discriminant analysis showed
      that age, history of intraocular surgery, preoperative maximum IOP, and mean
      deviation are the predictive factors for maculopathy. As compared with the
      hypotonous eyes without maculopathy, those with maculopathy tended to be younger
      and to have less severe visual field changes.

PMID- 7732924
TI  - [Prediction of postoperative visual acuity in retinal detachment with macular
      involvement].
AB  - We used laser interferometry (LI) and a potential acuity meter (PAM) to predict
      visual acuity after surgery for patients with rhegmatogenous retinal detachment
      with macular involvement. Thirty one eyes of 31 patients with retinal detachment
      were treated with scleral buckling procedures. Postoperative visual acuity was
      correlated with preoperative measurements of the LI and PAM, preoperative visual
      acuity by Landort's ring, and the estimated duration of macular detachment. The
      correlation between the duration of macular detachment and the postoperative
      visual acuity was not good (r = 0.55, p < 0.01). Although the preoperative visual
      acuity showed a relatively good correlation with postoperative visual acuity (r =
      0.62, p < 0.01), the results of the LI and PAM provided a better correlation (LI;
      r = 0.73, PAM; r = 0.71). Our results suggest that the LI and PAM are useful to
      predict the visual acuity after retinal reattachment in patients with
      preoperative macular detachment.

PMID- 7732925
TI  - [Biomicroscopic findings of premacular posterior vitreous].
AB  - The presence of vitreous gel in front of the macular area is still controversial.
      In order to understand the anatomy of the premacular vitreous, the posterior
      vitreous was observed biomicroscopically and slit-lamp photographs were taken in
      100 eyes without posterior vitreous detachment. We defined the premacular
      vitreous as the lacuna seen when optically empty space, a demarcated oval shaped
      dark area without Tyndall phenomenon, was observed in front of the macula.
      Although the premacular vitreous showed liquefaction, the Tyndall-phenomenon,
      indicating the presence of formed vitreous gel, was observed in most cases.
      Premacular lacuna was observed in 3 cases with high myopia, and in one case with
      vitreoretinal degeneration syndrome. The bursa premacularis or premacular
      precortical vitreous pocket observed in autopsy eyes could barely be observed in
      living eyes.

PMID- 7732926
TI  - [Anterior chamber inflammation after vitrectomy in posterior vitreous membrane
      syndrome and phacoemulsification and intraocular lens implantation].
AB  - We studied the anterior chamber inflammation with a laser flaremeter after
      transvitreal membrane peeling surgery for posterior vitreous membrane syndrome
      and cataract intraocular lens surgery, through separate surgery and combined
      surgery. In 16 eyes with vitrectomy and membrane peeling, mean flare count had
      one peak of 11 photons/msec at postoperative days 5 through 7. In 10 eyes with
      phacoemulsification and aspiration with posterior chamber lens implantation, the
      mean flare count had two peaks of 11 photons/msec at postoperative day 1 and in
      postoperative week 2. In 25 eyes with combined surgery of vitrectomy and cataract
      intraocular lens surgery, the mean flare count was similar to the summation of
      that of each simple surgery. In these 25 eyes, in 9 eyes with sutures, the mean
      flare count had two peaks of 37 photons/msec at postoperative day 1 and 27
      photons/msec at postoperative week 2, and in 16 eyes with self sealing wounds,
      the mean flare count had one peak of 22 photons/msec at postoperative week two.
      In 14 vitrectomized eyes with cataract-intraocular lens surgery, the mean flare
      count was as high as in combined surgery. In eyes with self sealing wounds, the
      flare count at postoperative day one was significantly lower than that of sutured
      eyes.

PMID- 7732927
TI  - [Optic disc and choroidal circulation detected by dye-filling rate in indocyanine
      green angiography].
AB  - Dye-filling rate of optic disc and choroid in normal human subjects was
      investigated using indocyanine green infra-red videoangiography and computerized
      image analysis. Only relative changes in the circulation of disc and choroid
      could be studied and the ratio (D/M) of dye-filling rate in normal subjects (age
      ranged 23-62) in disc (D) to choroid (M) was reliable. Intraocular pressure (IOP)
      was elevated to two levels with a pneumatic suction-cup. When D/M at normal IOP
      was 1, mean D/M was 1. 29 when mean IOP was 26.8 mmHg, and 1.48 when mean IOP was
      38.4 mmHg. The results suggest that IOP elevation produced less change in the
      disc circulation than in the choroid. The ratio of dye-filling rate of the disc
      at 38.4 mmHg to normal IOP was significantly correlated (P < 0.05) with perfusion
      pressure at normal IOP, showing that the autoregulatory mechanisms in the disc
      blood flow may possibly reach the limit especially in subjects whose perfusion
      pressure is low.

PMID- 7732928
TI  - [Ocular histopathological studies in leprosy in the silent stage--II.
      Immunohistochemical studies].
AB  - The distribution of leprosy antigen in 21 eyes from 12 autopsy cases of
      lepromatous leprosy patients (5 eyes from 3 cases in the silent stage, 16 cases
      from 9 cases in the active stage) were examined with acid-fast staining and
      immunohistochemistry. Anti-BCG antibody, anti-phenolic glycolipid-I (PGL-I)
      antibody, and anti-lipoarabinomannan-B (LAM-B) antibody were used as primary
      antigens. In the active stage, anti-BCG antibody and anti-LAM-B antibody showed
      almost the same staining pattern. Some cases, which showed negative reaction to
      acid-fast staining, occasionally showed positive staining pattern with anti-BCG
      antibody and anti-LAM-B antibody, which had high sensitivity and the advantage of
      detection of leprosy antigen. Some anti-PGL-I antibody showed a different
      staining pattern from acid-fast staining, anti-BCG antibody and anti-LAM-B
      antibody. These findings seemed to be caused by the difference in structure of
      the epitope. In the silent stage, clinically nonpigmented epithelium of 6 cases
      from 4 eyes showed positive staining pattern with anti-PGL-I antibody. These
      findings suggested that leprosy antigen still remained in this stage.

PMID- 7732929
TI  - [Pattern-reversal visual evoked potentials dissociated vertical deviation].
AB  - We recorded pattern-reversal visual evoked potentials (P-VEP) from dissociated
      vertical deviation (DVD) patients to evaluate the sensory system abnormalities in
      DVD. 91 DVD patients with good visual acuity were studied. Normal subjects and
      horizontal strabismic patients without DVD were compared for evaluation.
      Transient and steady state P-VEPs were recorded from three EEG electrodes placed
      on the posterior scalp. Half-field checker-board reversal stimulation was applied
      to stimulate monocular temporal retina and responses from right and left
      hemispheres were also compared for evaluation. Paradoxical lateralization was
      observed in all normal subjects. Abnormal P-VEPs were observed in 4 of 20 (20%)
      horizontal strabismic patients without DVD when employing the transient
      stimulation method and in 2 of 8 (25%) when using steady state stimulation.
      Abnormal P-VEPs were observed in 31 of 67 (46.3%) DVD patients, with the
      transient stimulation method and in 20 of 25 (80.0%) DVD patients with the steady
      state stimulation method. The abnormalities were various and diverse. Our
      observations indicate that DVD patients frequently have an abnormal sensory
      system detected by P-VEP, and DVD might be a complex and multi-origin condition
      involving both sensory and motor systems.

PMID- 7732930
TI  - [Study on color misnaming among the congenital color vision anomalous--Part 1.
      The tendency in color misnomer].
AB  - I report the hue and the color misnomers of 16 subjects with protanopia (color
      misnomers: 500) and 66 subjects of deutanopia (color misnomers: 2,056), and the
      color misnomers used by over 10 subjects each and their numbers. Green was the
      most frequent misnomer, followed by grey, yellow-green, purple, and brown. The
      deutanopia patients frequently used the Munsell color notation RP for grey. Many
      of the subjects who misnamed 11 times or more failed the Panel D-15 test. They
      were diagnosed as having strong color anomaly in the Ohkuma isochromatic plates
      and in the Tokyo Medical College isochromatic plates. The misnomers were most
      frequent among the neighboring hues. The severer the anomaly, the further the
      separation from the test color, and then the misnomers crossed the achromatic
      confusion line. Judging from the misnomer variation, the color sense of color
      anomaly does not necessarily seem to be constant. Moreover, liaison was noticed
      among red, brown, green, or occasionally purple in terms of misnaming pattern.
      Grey and pink were also linked in misnaming. Lightness was considered to play a
      strong role in these confusions.

PMID- 7732931
TI  - [Panel D-15 test under reduced illumination for persons with color vision
      defects].
AB  - We evaluated the panel D-15 test under reduced illumination in subjects with
      color vision deficiency and in normal subjects. Forty subjects with color vision
      deficiency (3 protanopes, 10 protanomalies, 10 deuteranopes, 7 extreme
      deuteranomalies and 10 deuteranomalies) and 10 normal subjects were the subjects
      for the experiment. Seven light levels ranging from 0.9 to 900 lux were used. All
      normal subjects passed the test at 3.5 lux or more and 30% failed at 0.9 lux.
      Color vision defective subjects began to fail the test at 225 lux, with 56%
      failing at 3.5 lux and 92% at 0.9 lux. The performance on the panel D-15 test
      decreased in proportion to decreasing the illumination in some color vision
      defective subjects. Some protanomalous subjects showed a deutan pattern at low
      illumination levels.

PMID- 7732932
TI  - [Two cases of Kniest dysplasia--ocular manifestations].
AB  - We report ocular findings from 2 children with Kniest dysplasia. Both eyes of the
      2 patients had abnormal long axial length causing high myopia, and vitreoretinal
      degeneration. The vitreous cavity of case 1 (a 15-year-old boy) which contained
      fibrous clouded membranous structures floating in the retrolental space and dense
      opacity at the temporal-inferior portion, was optically empty. Case 2 (a 7-year
      old boy) had cortical and posterior subcapsular opacity of the lens, and also
      veil-like vitreous opacity in the periphery. Their common retinal changes were
      characterized as perivascular lattice degeneration and white without pressure in
      various degrees. They have not yet shown cataract or retinal detachment which
      needs surgical treatment, but close ophthalmological follow up will be necessary
      for their favorable prognosis. The literature on vitreoretinal degeneration such
      as Wagner's disease or Stickler syndrome may indicate the relation of Kniest
      dysplasia to similar diseases. Because they might have different clinical courses
      and visual prognosis according to the original biosynthetic disorders, we
      emphasized the importance of orthopedic diagnosis regarding such vitreoretinal
      degeneration with constitutional bone diseases.

PMID- 7732934
TI  - Medicare maulers beware.

PMID- 7732933
TI  - Conflicts in medical marriages.

PMID- 7732935
TI  - Pericarditis following blunt thoracic trauma.
AB  - Pericarditis is a common clinical entity which has been reported frequently in
      association with numerous disease processes. However, pericarditis following
      blunt thoracic trauma is exceedingly rare and difficult to diagnosis. An 18 year
      old female was transferred to UAB Hospital for evaluation and management of
      multiple injuries following a high-speed single-vehicle motor vehicle accident.
      Injuries included a fractured right tibia and femur, pelvic fracture, and a right
      pulmonary contusion with rib fractures. Orthopedic procedures were performed.
      Ventilatory support was provided due to a severe pulmonary contusion. The post
      operative course was unremarkable. The patient was discharged two weeks after
      admission. One week after discharge, the patient was readmitted with pleuritic
      chest pain of several days duration. Diagnostic studies were performed. The
      patient was successfully treated with non-steroidal anti-inflammatory medications
      for pericarditis. Dramatic improvement ensured over two days. Follow-up showed no
      recurrence of pericardial symptoms, pleural effusion, or chest pain. In
      retrospect, complaints of episodic chest pain which were felt to be clinically
      insignificant during admission, may have been early signs of posttraumatic
      pericarditis secondary to blunt thoracic trauma.

PMID- 7732936
TI  - Dying, an important phase of living.

PMID- 7732938
TI  - Screening for hearing impairment in newborns.

PMID- 7732937
TI  - Marriage of practice guidelines and outcomes research.

PMID- 7732939
TI  - Primary melanoma of the rectum.

PMID- 7732940
TI  - Interaction between terfenadine and topical antifungal agents.

PMID- 7732941
TI  - Traumatic aneurysm of the superficial temporal artery.

PMID- 7732942
TI  - Nitroglycerine patches for brown recluse spider bites.

PMID- 7732943
TI  - Transient neonatal pustular melanosis: an uncommon rash.

PMID- 7732945
TI  - AAFP white paper on the provision of mental health care services by family
      physicians. AAFP Commission on Health Care Services.

PMID- 7732944
TI  - Use of diagnostic ultrasound examinations in family practice.

PMID- 7732946
TI  - Early identification and management of hearing impairment.
AB  - Early detection and treatment of hearing loss can prevent a lifetime of
      difficulties. Severe sensorineural hearing loss is present in approximately one
      in 1,000 newborns. Many newborns have mild to moderate hearing loss, either
      conductive or sensorineural, that interferes with normal functioning. The family
      physician is in an excellent position to identify hearing impairment at an early
      stage. During well-child visits, simple checklists and screening tests can be
      completed to aid in detection of a hearing loss. The Joint Committee on Infant
      Hearing and the National Institutes of Health Consensus Statement recommend
      screening all infants for hearing loss, preferably during the newborn period.
      Children at high risk for hearing loss should be referred for auditory function
      tests, such as behavioral observation audiometry, auditory brain stem response,
      otoacoustic emissions testing, visual reinforcement audiometry and conditioned
      play audiometry. The advantages and limitations of each test should be understood
      by the family physician. An infant is never too young to be treated for hearing
      loss. The earlier intervention begins, the greater the chance a child will
      develop to maximum potential.

PMID- 7732947
TI  - Practice guidelines: what the family physician should know.
AB  - Practice guidelines that specify how to treat medical conditions and perform
      procedures are appearing with greater frequency in the medical literature. Their
      use by managed care plans, hospitals and government programs is expected to
      affect the practice of medicine substantially in the coming years. This article
      reviews the key information that family physicians should have in order to
      evaluate and use practice guidelines effectively: how they are developed; how
      they differ from textbooks, review articles and other sources of expert
      consultation; whether they promote "cookbook medicine"; when to modify one's
      clinical practice in response to new guidelines, and how to cope with conflicting
      recommendations. Practice guidelines can improve the quality of care by
      summarizing current evidence and expert opinion, but they can also reduce the
      quality of care if the recommendations are poorly supported by scientific
      evidence and clinical reasoning. Economic and medicolegal concerns can also
      influence the potential benefits and harms of practice guidelines. Since hundreds
      of practice guidelines are anticipated to be developed in the coming years,
      family physicians should become informed consumers of guidelines, avoid accepting
      them on face value, and ask specific questions to judge their quality.

PMID- 7732948
TI  - Common questions patients ask during pregnancy.
AB  - When women become pregnant, they expect their family physicians to answer many
      questions about potential risks during the pregnancy and possible effects on the
      developing fetus. Many of these questions concern over-the-counter medications,
      common household exposures and daily activities, which often are not well
      discussed in obstetric texts. In general, women can be reassured that allergy
      medications and most common food additives, such as caffeine and aspartame, are
      safe to use during pregnancy. Most cosmetics and hair care products, including
      permanent wave solutions, are safe in limited exposures. Patients should be
      counseled to avoid exposure to insecticides and to continue good safety habits,
      such as wearing seat belts. Discussion of specific risks may prevent unnecessary
      anxiety and needless changes in work and home environment and lifestyle for
      pregnant women.

PMID- 7732949
TI  - Postoperative respiratory insufficiency.
AB  - Respiratory insufficiency is one of the most common and most serious
      complications of the postoperative period. Preexisting risk factors include
      cardiopulmonary disease, significant smoking history, obesity and advanced age.
      The risk of postoperative respiratory insufficiency is increased in emergency
      surgical procedures (particularly those related to trauma), procedures involving
      the chest or upper abdomen and procedures requiring prolonged anesthesia.
      Postoperatively, prolonged sedation or neuromuscular blockade, cardiovascular
      instability, respiratory problems and immobilization are important risk factors.
      Common clinical causes of respiratory insufficiency are atelectasis, aspiration,
      pulmonary edema and pulmonary embolism. Management strategies are directed at
      treatment of the cause of the insufficiency and restoration of pulmonary
      function. All surgical patients should be carefully assessed before surgery,
      monitored closely during and after the procedure, and aggressively treated to
      prevent or correct respiratory insufficiency.

PMID- 7732950
TI  - Nutrition in adults. U.S. Public Health Service.

PMID- 7732951
TI  - Migraines and other headaches: an approach to diagnosis and classification.
AB  - Headache is a symptom that accounts for over 18 million visits to physicians each
      year. In an effort to resolve inconsistencies and problems with the
      differentiation of specific types of headache, the International Headache Society
      (IHS) has established a classification system. For each major type of headache,
      the IHS classification specifies diagnostic criteria and recognized subtypes
      where appropriate. Migraine headaches are commonly encountered in clinical
      practice. Recognition and accurate diagnosis of migraine headache depend on a
      thorough history, appropriate physical examination and diagnostic testing.

PMID- 7732952
TI  - Alopecia: diagnosis and management.
AB  - Hair loss is a common problem that may affect both males and females in all age
      groups. Although androgenetic alopecia (common baldness) is the most frequently
      occurring type of hair loss, hair loss can result from a variety of local and
      systemic conditions. A detailed history, complete physical examination and
      directed use of laboratory tests are indicated in making the diagnosis.
      Specialized tests such as "hair pluck" and scalp biopsy may also be required.
      Treatment is focused on removing the cause of secondary hair loss, patient
      education and specific interventions for individual types of alopecia. All
      treatment strategies should address the significant cosmetic and psychologic
      impact of hair loss.

PMID- 7732953
TI  - Carcinoma of the endometrium.
AB  - Carcinoma of the endometrium is the most common gynecologic malignancy. The
      majority of women present with stage I disease, and the most common presenting
      symptom is postmenopausal bleeding. Early detection of endometrial cancer is
      important, because up to 90 percent of patients with stage I disease can be
      successfully treated. Certain risk factors, such as obesity, hypertension and
      diabetes mellitus, are associated with the development of this malignancy. Office
      endometrial sampling has a sensitivity of up to 97 percent for diagnosing
      carcinoma of the endometrium and can often eliminate the need for dilatation and
      curettage. Endometrial cancer is treated by total abdominal hysterectomy,
      bilateral salpingo-oophorectomy and, in many cases, postoperative radiation
      therapy.

PMID- 7732954
TI  - Near-drowning.
AB  - Near-drowning and drowning are major causes of neurologic injury and death in
      young persons. Most victims aspirate water, and pulmonary edema develops in many
      of these cases. Prolonged submersion causes cerebral asphyxia and adversely
      affects the brain within five minutes. Immediate ventilation and oxygenation are
      essential in the reversal of cerebral anoxia. During field resuscitation,
      precautions should be taken to protect the cervical spine because of the
      possibility of injury. The Heimlich maneuver is used only after unsuccessful
      attempts at ventilation suggest foreign-body obstruction. Prehospital advanced
      cardiac life support with tracheal intubation is indicated in patients with
      severe injuries. On arrival at the hospital, ventilation with continuous positive
      airway pressure or positive end-expiratory pressure enhances pulmonary function.
      Many water submersion accidents are avoidable; close supervision of infants and
      toddlers, installation of a fence around home swimming pools, and abstinence from
      alcohol during participation in water sports are some practical precautions.

PMID- 7732955
TI  - Human behavior and mental health. American Academy of Family Physicians and the
      American Psychiatric Association.

PMID- 7732956
TI  - American Psychiatric Association releases treatment guideline for bipolar
      disease.

PMID- 7732957
TI  - Balloon-expandable stent repair of severe coarctation of aorta.
AB  - Experimental studies have shown that stents implanted at the aorta become
      incorporated within the aortic wall and can be further expanded in growing
      animals. This study evaluates the feasibility and immediate results of balloon
      expandable stent implantation in 10 patients with severe coarctation of aorta.
      The ages of the patients ranged from 1 month to 43 years; 1 was an infant, 8 were
      children (mean age 5.3 +/- 4 years), and 1 was an adult. All had an unfavorable
      anatomy for balloon angioplasty; 9 had isthmus hypoplasia. Balloon predilation
      was first performed and its immediate effect evaluated. Then a balloon-expandable
      stent that was 30 mm long and covered the isthmus and coarctation levels was
      deployed, and it was further expanded to the preselected final diameter (12 +/- 4
      mm). A final hemodynamic and angiographic evaluation was then obtained. Full
      deployment of an incompletely expanded and distally displaced stent in the infant
      led to aortic disruption that was controlled by a second stent covering the
      disrupted zone and the isthmus. After balloon angioplasty alone was done, the
      mean gradient (43 +/- 12 vs 31 +/- 10 mm Hg) and the percentage stenosis (72% +/-
      11% vs 54% +/- 11%) had an insufficient decrease. However, after stent
      implantation was done, the gradient almost disappeared (mean 2 +/- 3 mm Hg). The
      angiographic stenosis disappeared in 7 patients and was markedly reduced in 3.
      The ratio of isthmus/descending aorta changed from 0.65 +/- 0.14 to 1 +/- 0.08 (p
      < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732958
TI  - Diastolic dysfunction is a feature of the antiphospholipid syndrome.
AB  - Recurrent thrombi, thrombocytopenia, pregnancy loss, and stroke in association
      with medium to high concentrations of anticardiolipin antibodies are well
      recognized features of antiphospholipid syndrome. Cardiac manifestations of
      primary antiphospholipid syndrome (PAPS) also have been documented but involve
      structural and valvular heart disease. Diastolic dysfunction in PAPS has not been
      well described. Therefore, 10 patients with PAPS (nine women and one man) of mean
      age 30 +/- 7 years (range 20 to 46 years) and 10 healthy age-, sex-, weight-, and
      height-matched control subjects were studied by echocardiography. Anticardiolipin
      antibody concentrations of patients with PAPS were > 80 immunoglobulin G
      phospholipid units as determined by enzyme-linked immunosorbent assay. Doppler
      derived parameters of left ventricular filling showed a significant association
      between PAPS and diastolic dysfunction compared with control, as evidenced by a
      decrease in peak early filling velocity (52 +/- 10 cm/sec vs 67 +/- 12 cm/sec; p
      < 0.01), a decrease in the ratio of peak early to peak atrial filling velocities
      (1.03 +/- 0.40 vs 1.52 +/- 0.28; p < 0.005), a decrease in the mean deceleration
      rate of early filling (338 +/- 75 cm/sec2 vs 590 +/- 227 cm/sec2; p < 0.005), and
      an increase in the percentage of atrial contribution to filling and deceleration
      time. Left ventricular mass, diastolic filling time, and heart rate did not
      differ between groups. Left ventricular systolic function was normal and ejection
      fraction did not differ between patients with PAPS and control subjects (63% +/-
      2% vs 65% +/- 7%; p not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732959
TI  - Quantitation of aortic regurgitation by Doppler echocardiography: a practical
      approach.
AB  - Aortic regurgitation is most frequently assessed noninvasively by Doppler
      echocardiography by use of continuous wave and Doppler color flow mapping. To
      compare both Doppler methods, 161 patients who had undergone cardiac
      catheterization and complete echocardiographic studies were studied. The
      continuous wave parameters analyzed included the slope of the diastolic
      deceleration and the pressure half-time of the regurgitant jet. From color flow
      Doppler, conventional parameters such as JH and its ratio to LVOH, JASA and its
      ratio to LVOA, and the regurgitant JA and its ratio to the LVA were obtained. The
      JH/LVOH was the color flow parameter that best correlated with angiography (r =
      0.91). A ratio of < or = 25% was used to predict mild aortic regurgitation with
      96% accuracy. A ratio of > or = 40% was also used to predict severe aortic
      regurgitation (3 to 4+) with 96% accuracy. Absolute JH at the origin of the
      regurgitant jet was the second best color flow parameter that correlated with
      angiography (r = 0.89). When continuous wave-derived slope was used, a
      significant overlap among different degrees of aortic regurgitation was observed.
      Predictive accuracy for mild aortic regurgitation was 70% by using a slope < 2
      m/sec2 and 86% for severe aortic regurgitation when using a slope > 3 m/sec2. In
      conclusion, color flow Doppler appears to be superior to continuous wave Doppler
      in the assessment of aortic regurgitation. The JH/LVOH appears to be the best
      color parameter for quantifying aortic regurgitation. The measurement of the
      absolute JH at its origin appears to be the simplest and most practical method
      for assessing the degree of aortic regurgitation.

PMID- 7732960
TI  - Microwave ablation of canine atrial tachycardia induced by aconitine.
AB  - We tested the efficacy of microwave-frequency energy for ablating atrial
      tachycardia in eight open-chest dogs. Five other dogs served as controls. Atrial
      tachycardia was induced by direct application of aconitine crystals to the
      epicardial atrial surface or by injection of aconitine solution (0.15 mg/ml) into
      the right or left atrial myocardium. Atrial tachycardias (n = 15) developed at a
      cycle length of 253 +/- 64 msec or within 245 +/- 116 sec after topical
      application or injection of aconitine. Catheter ablation was attempted on 10
      atrial tachycardias in 8 experiment dogs by using continuous, unmodulated
      microwave energy from a 915 MHz frequency signal generator via a 7F helical or
      whip antenna catheter. Successful ablation was defined as conversion of atrial
      tachycardia to sinus rhythm during delivery of microwave energy and maintenance
      of sinus rhythm for > 5 minutes after termination of energy delivery. All 10
      atrial tachycardias were successfully ablated by 2.3 +/- 1.6 applications of
      microwave energy for each atrial tachycardia induced. Forward microwave power
      level was 50.5 +/- 8.1 W, and the duration of energy application was 25.0 +/-
      27.6 seconds. Sinus rhythm resumed 9.5 +/- 9.2 seconds after the onset of
      microwave energy application. After a mean follow-up of 10.4 minutes, seven
      atrial tachycardias recurred, most likely the result of diffusion of aconitine
      beyond the perimeter of rhe ablation lesions. Atrial tachycardia did not recur in
      3 of 3 dogs that had larger ablation lesion. Gross examination revealed 10
      demarcated round or oval transmural lesions in the right or left atrium, ranging
      from 12.6 to 105.6 mm2 in area.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732961
TI  - Recurrent reversible cardiogenic shock triggered by emotional distress with no
      obstructive coronary disease.

PMID- 7732962
TI  - Spontaneous transient, inverted U waves as initial electrocardiographic
      manifestation of unstable angina.

PMID- 7732963
TI  - Reversible dilated cardiomyopathy: an unusual case of thyrotoxicosis.

PMID- 7732964
TI  - Isolated mitral valve rupture caused by nonpenetrating trauma: recognition by
      transesophageal echocardiography.

PMID- 7732965
TI  - Mixed-type total anomalous pulmonary venous connection: echocardiographic
      limitations and angiographic advantages.

PMID- 7732966
TI  - Three-dimensional echocardiography in the diagnosis of postinfarction ventricular
      septal defect.

PMID- 7732967
TI  - Magnetic resonance imaging in Bland-White-Garland syndrome.

PMID- 7732968
TI  - Echocardiographic diagnosis of type B interruption of a right aortic arch.

PMID- 7732969
TI  - Effects of sotalol on the function of implanted pacemakers.

PMID- 7732970
TI  - Recognition of the segmental tendency of false-positive dobutamine stress
      echocardiograms and its effects on test sensitivity and specificity.

PMID- 7732971
TI  - Intracoronary ultrasound imaging before and after directional coronary
      atherectomy: in vitro and clinical observations.
AB  - The rate of restenosis after directional coronary atherectomy (DCA) is higher
      than expected. To elucidate why, the current study used intravascular ultrasound
      (IVUS) imaging to investigate the mechanism of DCA. An in vitro validation study
      was performed to determine the accuracy of the measurement of plaque removal by
      IVUS. DCA was performed in eight human atherosclerotic artery segments. The
      volume of removed plaque was measured by water displacement and was compared with
      the volume calculated from IVUS images. A clinical study of DCA was performed in
      32 lesions. IVUS was performed in 28 lesions after successful DCA. Measurements
      of lumen dimensions from digital angiograms before and after DCA were compared
      with observations of lumen and plaque size from the cross-sectional IVUS images.
      In the in vitro study, the mean plaque volume removed by DCA was 19.9 +/- 8.5
      microliters. The calculated estimate of removed plaque volume by IVUS was 18.6 +/
      7.9 microliters and correlated closely with the volume by water displacement (r
      = 0.92). The calculated volume of plaque removed from histologic sections was
      14.3 +/- 6.0 microliters and was linearly correlated with plaque volume by water
      displacement (r = 0.81). In the clinical study, the angiographic mean minimum
      lumen diameter increased from 1.0 +/- 0.4 to 2.7 +/- 0.5 mm and the percentage
      stenosis decreased from 70% to 19% (p < 0.0001). The IVUS images before and after
      DCA showed that the lumen DCA improved from 2.9 +/- 1.5 to 7.0 +/- 1.5 mm2 (p <
      0.0001). In addition the vessel cross-sectional area (CSA) increased from 17.1 +/
      5.9 to 18.7 +/- 5.5 mm2. The atheroma CSA was reduced from 14.2 +/- 5.0 to 11.7
      +/- 4.8 mm2. This combined effect of reduction in atheroma CSA and stretching of
      the outer vessel diameter resulted in an improvement in percentage plaque area
      stenosis from 83% +/- 7% to 61% +/- 9%. It is concluded that despite a successful
      angiographic appearance, DCA removed an average of 2.5 mm2 from the atheroma,
      which corresponds to only 18% of the atheroma CSA. The total lumen CSA increased
      4.1 mm2; 61% of the new lumen was created by cutting and removal of plaque,
      whereas 39% of the new lumen was made by stretching the external wall of the
      artery. Despite an excellent angiographic result, IVUS imaging reveals that after
      DCA a significant amount of residual atheroma remains. As in balloon dilatation,
      a stretching effect is a significant component of DCA.

PMID- 7732972
TI  - Regional and arterial localization of radioactive microparticles after local
      delivery by unsupported or supported porous balloon catheters.
AB  - Catheter-mediated intramural delivery of pharmaceutical agents after angioplasty
      is a potential method to reduce postangioplasty restenosis. The efficacy of such
      delivery has been limited both by an incomplete initial intramural deposition of
      delivered agents and by rapid diffusion of soluble agents from the site of
      delivery. The local delivery of microparticulate agents results in prolonged
      retention of material at the delivery site. Accordingly this study was designed
      to evaluate the complementary issue of the initial delivery efficiency and
      pattern of localization of microparticles after local catheter-mediated delivery
      with two types of porous balloons. These two types were a "standard" porous
      balloon (PB) in which hydraulic pressure both inflated the balloon and infused
      the agents and a porous balloon with a mechanical undergirding that permitted
      mechanical expansion (PB/ME) before agent infusion. Radioactive cerium 141
      labeled microparticles (11.4 microns diameter) were locally delivered into
      atherosclerotic rabbit femoral arteries after angioplasty to test the hypothesis
      that use of the PB/ME apparatus would yield enhanced intramural particle
      deposition and decreased systemic administration by increased balloon-wall
      contact before microparticle infusion. Six animals underwent infusion with the PB
      catheter, and seven animals underwent infusion with the PB/ME catheter. An image
      of the in vivo particle distribution was obtained with a gamma camera during
      infusion, immediately after infusion, and 1, 3, and 7 days after infusion. Tissue
      samples from the artery, periadventitia, thigh, calf, and foot musculature, and
      liver were obtained at animal death, and retained radioactivity was measured with
      a well counter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732973
TI  - Seeding of intracoronary stents with immortalized human microvascular endothelial
      cells.
AB  - Intracoronary stents are effective in decreasing the complications associated
      with acute closure during coronary angioplasty. A major complication associated
      with the use of coronary stents is acute thrombotic occlusion. It has been
      postulated that the stent loses its thrombogenic potential after it becomes
      covered with a layer of endothelial cells. Human dermal microvascular endothelial
      cells were transfected with a plasmid containing the simian virus 40 large T
      antigen gene. Stents were placed in culture media with cells for 2 weeks. Seeding
      efficiency of the stent with the endothelial cells was assessed by scanning
      electron microscopy. Balloon-expandable coronary stents placed in cell culture
      with immortalized human microvascular endothelial cells showed near-complete
      coverage after 2 weeks. After balloon inflation, persistence of cells on the
      stent was noted only on the lateral aspect of the balloon-expanded stents. If
      these stents were placed in culture, complete recovery of the monolayer was noted
      after 3 days. Stents were then covered with endothelial cells and frozen for 4
      days. After thawing, the cells adhered to the devices and divided to form a
      monolayer in tissue culture. Seeded balloon-expandable stents were frozen for 4
      months, thawed, and then implanted in a pig coronary artery. Human endothelial
      cells were identified on the stent 4 hours after deployment. These studies
      demonstrate the feasibility of using a human microvascular endothelial cell line
      to seed an uncoated metal stent. The cells remain adherent to the stent, are
      functional after freezing, and remain on the stent at least 3 hours after
      intracoronary implantation.

PMID- 7732974
TI  - Comparison of the thrombogenicity of stainless steel and tantalum coronary
      stents.
AB  - This study was designed to compare the thrombogenicity of stainless steel and
      tantalum coronary stents of the same design. Stainless steel and tantalum
      coronary stents are being evaluated for their utility in treating acute closure
      and restenosis. A major disadvantage of stainless steel stents is radiolucency.
      To determine whether radioopaque tantalum stents may be safely substituted for
      stainless steel stents, we compared the relative thrombogenicity of these
      materials in stents of identical design. Total platelet and fibrin deposition on
      the stents were determined from measurements of indium 111-labeled platelet and
      iodine 125-labeled fibrinogen accumulation after deployment into exteriorized
      chronic arteriovenous shunts in seven untreated baboons. In another series of
      experiments, 111In-platelet deposition was compared 2 hours after stent
      implantation in coronary arteries of pigs. In baboons, platelet thrombus
      formation on stainless steel and tantalum stents was equivalent and plateaued at
      approximately 2.5 x 10(9) platelets after 1 hour (p > 0.05). Fibrin deposition
      averaged approximately 1 mg/stent and did not differ between the stainless steel
      and tantalum stents (p > 0.05). In the porcine coronary model there was no
      significant difference in 111In-labeled platelet deposition between the stainless
      steel and tantalum stents (p > 0.05). This result was confirmed by scanning
      electron microscopic analysis of the coronary stents. Based on these two models,
      we conclude that there is no significant difference in the thrombogenicity of
      stainless steel and tantalum wire coil stents.

PMID- 7732975
TI  - Increased number of thromboxane A2-prostaglandin H2 platelet receptors in active
      unstable angina and causative role of enhanced thrombin formation.
AB  - The current study was designed to investigate the number and affinity of platelet
      thromboxane A2/prostaglandin H2 (TxA2/PGH2) receptors in patients with unstable
      angina and, if any, the role played by the increased thrombin formation that is a
      common finding in these patients. Measurements taken during active unstable
      angina but not those taken during inactive angina showed an increase number (p <
      0.001), without changes in affinity, of platelet TxA2/PGH2 receptors, evaluated
      as the binding capacity of iodine 125-PTA-OH, a stable TxA2 analogue. Moreover
      patients with active angina had higher plasma concentrations of fibrinopeptide A
      (FPA) (p < 0.0001), which were significantly related to the number of platelet
      TxA2/PGH2 receptors (r = 0.76; p < 0.01). Heparin infusion but not aspirin
      treatment promptly normalized the number of TxA2/PGH2 receptors and significantly
      reduced plasma FPA concentrations. In an in-vitro study thrombin in a
      concentration similar to that found in vivo significantly increased the number of
      platelet TxA2/PGH2 receptors (p < 0.01), whereas heparin did not affect TxA2/PGH2
      receptors. These results have important therapeutic implications and indicate the
      preferential use of heparin rather than aspirin during the acute phase of
      unstable angina.

PMID- 7732976
TI  - Long-term risk stratification with dipyridamole imaging.
AB  - This study was undertaken to assess the reliability of clinical parameters and
      dipyridamole-thallium 201 images for predicting the occurrence of future cardiac
      events (nonfatal myocardial infarction or cardiac death). Dipyridamole myocardial
      perfusion imaging is routinely performed in patients who have possible or known
      coronary disease and a low exercise tolerance. A total of 753 patients underwent
      clinical assessment and semiquantitative dipyridamole-201TI imaging and were
      followed up as outpatients. Patients who underwent coronary revascularization
      during the follow-up period were excluded from the study because the decision to
      intervene would have been based at least in part on the test itself. There were
      82 cardiac events and 54 noncardiac deaths, and 11 patients were lost to follow
      up after a mean follow-up of 15 months. With use of a quantitative index
      reflecting the amount of jeopardized myocardium, patients could be stratified by
      dipyridamole imaging into subsets with coronary morbidity and mortality rates
      ranging from 1% to 89%, (p = 0.0001). When clinical and scintigraphic variables
      were subjected to backward stepwise logistic regression analysis, the significant
      predictors of cardiac events were the jeopardized myocardium index by
      scintigraphy (p < 0.0001), left ventricular hypertrophy on the electrocardiogram
      (p = 0.0009), and transient dipyridamole-induced left ventricular cavitary
      dilatation (p = 0.0073). Quantitative dipyridamole-201TI imaging appears to be a
      powerful predictor of future cardiac events in patients with coronary disease and
      a low exercise tolerance and is a potentially useful contributor to risk-profile
      assessment and to the treatment of these patients.

PMID- 7732977
TI  - Hemodynamic significance of coronary jet velocity in patients: limitations of the
      Bernouilli equation in small conduits.
AB  - The objective of this study was to assess the use of coronary stenosis velocity
      in the determination of translesional pressure gradients. In the physiologic
      assessment of coronary stenosis, the accelerated intracoronary flow velocity
      within a narrowing has correlated with minimal lesion cross-sectional area
      according to the continuity equation. In large conduits the jet velocity can
      determine pressure gradients when used in the Bernouilli equation. However, the
      use of intralesional flow velocity for calculation of translesional pressure
      gradients by the simplified Bernouilli equation (delta P = 4V2) may be inaccurate
      in small (< 5 mm diameter) conduits. Translesional pressure (2.2F catheter) and
      flow velocity (0.018-inch guidewire) were measured in a single coronary artery in
      23 patients undergoing diagnostic angiography or angioplasty. The electronically
      determined mean of phasic proximal and distal pressure and planimetry of the
      instantaneous phasic pressure gradient were used and compared with the
      instantaneous velocity calculations of pressure by the simplified Bernouilli
      formula with both maximal jet velocity and a modified formula including proximal
      velocity. The mean measured translesional pressure gradient was 18 +/- 13 mm Hg
      (range 0 to 50 mm Hg) and was equivalent to the instantaneous average pressure
      gradient by planimetry. The maximal jet velocity was 125 +/- 40 cm/sec (range 63
      to 250 cm/sec), yielding a calculated pressure gradient of 3 +/- 3 mm Hg. The
      calculated pressure gradient by the simplified Bernouilli equation correlated
      poorly with the measured translesional gradient (r = 0.27, F = 1.63, p =
      0.21).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732978
TI  - Use of P-wave-triggered, P-wave signal-averaged electrocardiogram to predict
      atrial fibrillation after coronary artery bypass surgery.
AB  - Atrial fibrillation occurs commonly after coronary artery bypass surgery.
      However, despite numerous attempts at prediction, no accurate and generally
      accepted method exists to predict its occurrence. P-wave-triggered P-wave signal
      averaging was performed on 54 patients before coronary artery bypass surgery to
      evaluate the utility of this method to predict atrial fibrillation after coronary
      artery bypass surgery. After excluding six patients with unevaluable P-wave
      signal averages and three patients with postoperative arrhythmias other than
      atrial fibrillation, the P-wave signal averages of 45 patients were analyzed.
      Sixteen patients had postoperative atrial fibrillation and 29 did not. The mean P
      wave duration of the filtered, signal-averaged P wave was 163 +/- 19 msec in the
      16 patients with atrial fibrillation and 144 +/- 16 msec in the 29 patients
      without (p < 0.005). Left atrial enlargement on the surface electrocardiogram
      (ECG) was the only other statistically significant variable that correlated
      weakly with the onset of postoperative atrial fibrillation (p = 0.04). Other
      clinical variables such as P-wave duration in ECG lead II, left ventricular
      hypertrophy on ECG, age, sex, hypertension, and left ventricular ejection
      fraction were not significantly different between the two groups. With a cut
      point of 155 msec, chi-squared analysis revealed a p value of < 0.005, yielding a
      sensitivity of 69%, a specificity of 79%, a positive predictive value of 65%, and
      a negative predictive value of 82%. Signal-averaging of the P wave in patients
      before coronary artery bypass surgery provides a good predictor of postoperative
      atrial fibrillation.

PMID- 7732979
TI  - Diagnostic accuracy of a low-dose isoproterenol head-up tilt protocol.
AB  - The rate of positive head-up tilt (HUT), specificity, and same-day
      reproducibility of an HUT at 60 degrees combined with a low-dose isoproterenol
      infusion was assessed in the following patients: 120 consecutive patients with
      recurrent unexplained syncope, 30 healthy patients in a control group, and 30
      patients with documented syncope not related to a vasodepressor reaction. HUT was
      positive in 61% (73 of 120) of patients with unexplained syncope. The false
      positive rate in both the control and documented syncope groups was 6.6%. The
      mean isoproterenol dose infused was 1.4 +/- 0.5 microgram/min, 1.3 +/- 0.4
      micrograms/min, 1.3 +/- 0.5 microgram/min, respectively (p = NS). HUT was
      positive during the drug free stage in 30 (25%) of 120 patients, and
      isoproterenol infusion was necessary in the remaining 43 (36%) patients.
      Immediate reproducibility was assessed in 75 patients, and HUT response was
      reproduced in 37 (82%) of 45 patients with a baseline positive HUT and in 28
      (93%) of 30 patients with a baseline negative response. Overall, "sensitivity,"
      specificity, and reproducibility were 61%, 93%, and 86%, respectively. Clinical
      variables that increased the probability of a positive outcome were age < or = 50
      years and two or more syncopal episodes in the preceding 6 months in the absence
      of structural heart disease. These data support the use of an HUT protocol with
      low-dose isoproterenol infusion for the assessment of patients with recurrent
      syncope.

PMID- 7732980
TI  - Blood pressure and atrial natriuretic peptides correlate throughout the day.
AB  - Vessel dilator consisting of amino acids (a.a.) 31-67 and atrial natriuretic
      factor (ANF) composed of a.a. 99-126 of the 126 a.a. ANF prohormone circulate in
      humans and have potent vasodilatory properties. To determine whether these atrial
      natriuretic peptides are directly related to blood pressure in healthy
      normotensive humans, we recently had the unique opportunity to examine the
      circadian rhythms of vessel dilator, ANF, and blood pressure in seven individuals
      in 1988 and again in 1993. The changes in mean arterial pressure and systolic and
      diastolic blood pressure in these individuals during this 5-year hiatus allows
      comparison in the same individual, if circulating concentrations of atrial
      natriuretic peptides directly correlate with naturally occurring changes in blood
      pressure. In both 1988 and in 1993 vessel dilator and ANF each had significant (p
      < 0.001) circadian rhythms with their peak concentrations at 4:00 AM being nearly
      twice their concentrations at 4:00 PM. Mean arterial pressure, systolic blood
      pressure, and diastolic blood pressure also had significant circadian rhythms
      with peaks and troughs that were exactly opposite to those of ANF and vessel
      dilator. A significant inverse correlation between 24-hour averages of mean
      arterial blood pressure and 24-hour averages of vessel dilator (p = 0.05) and ANF
      (p = 0.02) was also found. These data suggest that vessel dilator and ANF are
      important for the maintenance of blood pressure within the normotensive range.

PMID- 7732981
TI  - Evaluation of the efficacy and safety of oral nicardipine in treatment of urgent
      hypertension: a multicenter, randomized, double-blind, parallel, placebo
      controlled clinical trial.
AB  - This study was a prospective, randomized, double-blind, placebo-controlled
      clinical trial designed to evaluate the safety and efficacy of oral nicardipine
      for the treatment of urgent hypertension in the emergency department. Of 57
      patients with urgent hypertension 53 patients were enrolled: 36 men and 17 women,
      43 black and 10 white, age range 48 +/- 11 years, and diastolic blood pressure
      128 +/- 7 mm Hg. Patients were randomly assigned to receive 30 mg nicardipine or
      placebo in blind fashion followed by 30 mg open-label nicardipine in
      nonresponders. Responders to one or two doses of nicardipine received 30 or 40 mg
      nicardipine three times a day for 1 week after discharge from the emergency
      department. Adequate blood pressure reduction, defined as a reduction of
      diastolic blood pressure to less than 100 mm Hg or by at least 20 mm Hg, was
      achieved in 65% and 22% of patients who received 30 mg nicardipine or placebo (p
      = 0.002). Adequate blood pressure reduction after administration of open-label
      nicardipine occurred in 76% of the nonresponders to placebo. Blood pressure
      reductions were maintained at 1 week after discharge. The drug was well
      tolerated, and no significant adverse events occurred. We conclude that oral
      nicardipine is a safe and effective drug for the initial treatment of urgent
      hypertension.

PMID- 7732982
TI  - Performance of the signal-averaged electrocardiogram: relation to baseline QRS
      duration.
AB  - Analysis of the duration and terminal components of the filtered QRS complex on
      the signal-averaged electrocardiogram (ECG) has been widely used for the
      detection of late potentials. Although filtered QRS duration is strongly related
      to 12-lead QRS duration, the relation of performance of the signal-averaged ECG
      to baseline QRS duration has not been critically examined. To examine the
      relation of test performance of the signal-averaged ECG to 12-lead QRS duration
      and to test the hypothesis that the difference between filtered and baseline 12
      lead QRS duration would reflect more accurately the presence of late potentials
      than would analysis of the filtered QRS alone, we evaluated signal-averaged and
      12-lead ECGs in 144 normal subjects and in 132 patients who were examined by
      electrophysiologic study and of whom 45 had inducible sustained monomorphic
      ventricular tachycardia. The signal-averaged ECG was considered positive by
      standard late potential criteria when the filtered vector QRS duration was > 114
      msec and either the root-mean-square voltage of the terminal 40 msec of the
      filtered QRS was < 20 microV or the low-amplitude signal of the terminal filtered
      QRS was > 38 msec. A new signal-averaged ECG criterion for the presence of late
      potentials was developed in the 144 normal subjects on the basis of the
      difference between the longest filtered QRS duration in any of the orthogonal
      leads and QRS duration on the baseline 12-lead ECG ("the QRS difference"), which
      was adjusted by regression analysis for the decreasing QRS difference found with
      increasing baseline QRS duration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732983
TI  - Left ventricular morphologic features and function in nonhospitalized cocaine
      users: a quantitative two-dimensional echocardiographic study.
AB  - To determine whether left ventricular (LV) hypertrophy or dysfunction is present
      in nonhospitalized cocaine users, we performed quantitative two-dimensional
      echocardiography in 20 intravenous cocaine users and 20 age- and sex-matched
      controls. Cocaine users were normotensive, had begun taking cocaine an average of
      14 years earlier, and had used cocaine an average of 8 times/mo during the
      preceding year. There were no significant differences between cocaine users and
      control subjects for LV mass index (79 vs 74 gm/m2, respectively), mean wall
      thickness (0.95 vs 0.91 cm), end-diastolic volume index (55 vs 56 ml/m2), end
      systolic volume index (17 vs 19 ml/m2), or ejection fraction (70 vs 66%; p > or =
      0.09 for all comparisons). Moreover, none of the cocaine users or control
      subjects had significant regional wall motion abnormalities, and none of the
      subjects or controls had ejection fractions < 55%. Thus we found little evidence
      that significant LV hypertrophy or dysfunction is present in nonhospitalized
      cocaine users. From these results we speculate that cocaine-associated LV
      hypertrophy and dysfunction may be restricted to certain high-risk groups of
      chronic cocaine users.

PMID- 7732984
TI  - Ultrastructure and immunohistochemistry of the coronary chemoreceptor in human
      and canine hearts.
AB  - Ultrastructure of the coronary chemoreceptor that causes a hypertensive reflex
      was studied immunohistochemically in human and canine hearts. Both cytologic and
      histologic features were similar in human beings and dogs, consisting of chief
      cells, sustentacular cells, Schwann cells, nerve fibers, blood vessels, and
      connective tissue. Three or four chief cells were typically surrounded by one
      Schwann cell, making a glomoid cluster about 20 microns across. Volume fractions
      of chief cells compared to capillaries were about 1:2 in dog and 1:4 in human
      chemoreceptors. Abundant osmiophilic dense granules filled the chief cells.
      Complex junctions between nerve fibers, chief cells, and sustentacular cells or
      Schwann cells exhibited a characteristic fine structure. Immunohistochemically,
      serotonin reactivity was observed mainly in the vicinity of junctions between
      nerve endings and chief cells, but some large granules in chief cells also
      stained positively. These new morphologic findings provide further support for
      the probable role of serotonin in the activation of the cardiogenic hypertensive
      chemoreflex in both human and canine hearts.

PMID- 7732985
TI  - Atrial wall tension changes and the release of atrial natriuretic factor on
      relief of cardiac tamponade.
AB  - Cardiac tamponade causes elevation and equalization of cardiac filling pressures,
      sodium and water retention, and a paradoxically low plasma atrial natriuretic
      factor (ANF) concentration despite increased intraatrial pressures. Recent
      reports suggested that plasma ANF concentrations rise after relief of tamponade.
      The purposes of the present study were (1) to determine the time course and
      extent of ANF release on relief of cardiac tamponade; (2) to measure the atrial
      transmural wall pressures, atrial sizes, and atrial wall tension changes
      associated with relief of tamponade; and (3) to determine the biologic activity
      of elevated plasma ANF during and after relief of tamponade. We sampled blood for
      ANF and cyclic guanosine monophosphate (cGMP) immediately before and up to 24
      hours after relief of cardiac tamponade in 10 patients. Atrial and pericardial
      pressures were measured immediately before and shortly after pericardiocentesis,
      and atrial dimensions were determined by two-dimensional echocardiography before
      and within 1 hour after the tap. Urine volumes were measured in 8-hour increments
      before and after the procedure. Relief of cardiac tamponade was associated with a
      prompt and massive increase in plasma ANF concentrations, reaching
      pharmacologically active levels. The rise in ANF was negatively correlated with
      atrial pressures but positively correlated with atrial transmural pressures,
      atrial size, and calculated wall tension. Plasma ANF levels peaked at 515 +/- 95
      pg/ml 40 minutes after relief of tamponade and leveled off at 140% to 180% of the
      pretap concentrations. Plasma cGMP exhibited a slightly delayed but similar time
      course to the rise in ANF levels, and urine flow rate increased fourfold in the 8
      hours after relief of tamponade.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732986
TI  - Echo Doppler evaluation of patients with acute mitral regurgitation: superiority
      of transesophageal echocardiography with color flow imaging.
AB  - Acute mitral regurgitation is a medical emergency that requires prompt, accurate
      diagnosis and urgent therapy. Although the use of echo Doppler imaging has been
      described in these patients, preliminary observations have suggested that color
      flow Doppler performed from the standard transthoracic windows may underestimate
      the severity of mitral insufficiency in this setting. The aim of this study was
      to compare transesophageal color Doppler quantitation of regurgitation with
      results obtained from standard transthoracic windows in patients with acute,
      severe mitral regurgitation. Two-dimensional echocardiography with pulsed,
      continuous, and color flow Doppler was performed by both transthoracic and
      transesophageal methods in 16 consecutive patients who were documented to have
      acute severe mitral insufficiency by catheterization. Transthoracic and
      transesophageal scans were reviewed by two blinded observers and assessed for the
      detection of mitral regurgitation by transthoracic pulsed wave (81%), continuous
      wave (100%), and color flow Doppler (81%) compared with transesophageal color
      flow imaging (100%; p = NS). Severity of mitral regurgitation was graded as none,
      mild, moderate, or severe on the basis of existing transthoracic pulsed wave and
      color flow criteria and compared with transesophageal color flow grading. At
      first examination patients were critically ill, with elevated pulmonary wedge
      pressures (mean 27 +/- 7 mm Hg) and V waves (mean 45 +/- 10 mm Hg). Fifteen of
      the patients underwent emergency surgery, and the overall hospital mortality rate
      was 12%. Maximal color flow jet areas were significantly greater on
      transesophageal scanning (mean 10.5 cm2) compared with transthoracic color jets
      (mean 2.3 cm2).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732987
TI  - Stability of index of heart rate variability in patients with congestive heart
      failure.
AB  - Stability of indexes of heart rate variability (HRV) has not been established for
      patients with congestive heart failure (CHF). We therefore measured Holter
      derived HRV indexes in 17 stable patients with class II or III CHF (mean age 52
      +/- 9 yr; 5 men and 12 women) on two occasions 2 weeks apart. Stability was
      determined via paired t tests and intraclass correlation coefficients (ICCs).
      ICCs for time domain indexes of HRV were > or = 0.86 for 24 hours, > or = 0.73
      for daytime, and > or = 0.72 for nighttime indexes reflecting longer-term
      variability. After log transformation, ICCs for the short-term 24-hour measures
      PNN50 (percentage of N-N intervals > 50 msec different from preceding interval)
      and RMSSD (the root mean square of successive differences) were 0.85 and 0.67.
      ICCs for frequency domain indexes of HRV were 0.86 to 0.91. We compared HRV
      indexes, serum norepinephrine (NE) levels, and respiratory sinus arrhythmia
      induced by paced breathing, also considered measures of autonomic tone. NE
      correlated weakly with average R-R interval, and all indexes of HRV reflecting
      longer-term variation (r = -0.32 to r = -0.50). ICC was 0.78 for NE. Respiratory
      sinus arrhythmia was highly repeatable (ICC = 0.70) but did not correlate
      significantly with NE or any measure of HRV. We conclude that time and frequency
      domain indexes of HRV are stable over time in CHF patients without intervening
      events.

PMID- 7732988
TI  - Myocardial myotonia in myotonic muscular dystrophy.
AB  - We sought to determine whether and to what degree myocardial myotonia might occur
      in myotonic muscular dystrophy. Cardiac involvement manifests itself chiefly as
      abnormalities of specialized tissues. Current echocardiographic techniques permit
      assessment of left ventricular diastolic filling properties and might detect
      subtle myocardial myotonia. Twenty patients (mean age 37 +/- 13 years) with
      myotonic muscular dystrophy were studied. Twenty normal subjects (mean age 34 +/-
      12 years), served as controls. Each subject had two-dimensional targeted M-mode
      echocardiograms of the posterior left ventricular wall to measure the rate of
      early diastolic relaxation, which was defined as diastolic endocardial velocity
      maximum (DEVM). Global left ventricular function was quantified. Doppler
      recordings of mitral inflow measured peak E and A velocities, ratio of E to A
      (E/A), mitral deceleration time (DT) and isovolumic relaxation (IVR) time. Normal
      controls had DEVM = 19 +/- 3 cm/sec, IVR = 72 +/- 7 msec, E/A = 1.6 +/- 0.5, and
      DT = 193 +/- 18 msec. Two SDs below the mean normal DEVM was 13.3 cm/sec. Two
      patient groups emerged: group A (10 patients) had abnormally slow DEVM (< or =
      13.2 cm/sec) and group B (10 patients) had normal DEVM (> 13.2 cm/sec) with DEVM
      = 11 +/- 2 cm/sec and 20 +/- 4 cm/sec, respectively. Mitral inflow parameters
      showed a longer DT and IVR, with lower E/A ratios for group A versus group B,
      with DT = 203 +/- 48 msec and 175 +/- 21 msec, IVR = 87 +/- 15 msec and 74 +/- 7
      msec, E/A = 1.7 +/- 0.7 and 2.3 +/- 0.9, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7732989
TI  - Chaotic atrial rhythm in children.
AB  - Chaotic atrial rhythm (CAR) usually occurs as a sequela of chronic obstructive
      lung disease in adults. We report the clinical manifestations and response to
      therapy in nine children with CAR treated predominantly with propafenone or
      amiodarone. Age at presentation ranged from 1 day to 30 months; six patients were
      < or = 2 weeks old. Six patients had tachycardia, and three had congestive heart
      failure. The atrial rate was 200 to 500 (mean 369 +/- 71) beats/min and the
      ventricular rate 150 to 300 (mean 251 +/- 37) beats/min. Eight patients had
      cardiac abnormalities. Intravenous drug therapy was not successful in converting
      CAR to sinus rhythm in any patient. A mean of four (range three to five) drugs
      was used in each patient; amiodarone and propafenone, alone or in combination,
      proved most successful. Seven patients were discharged from the hospital: full
      control was achieved in three (digoxin and amiodarone in two and digoxin,
      amiodarone, and procainamide in one), good control in three (digoxin, amiodarone,
      and propafenone in two and digoxin and propafenone in one), and ventricular rate
      control in one (digoxin, amiodarone, and propafenone). Two neonates with
      hypertrophic cardiomyopathy died. Long-term follow-up showed that CAR had
      resolved in five patients but persisted in two. We conclude that CAR remains
      difficult to control despite the use of newer antiarrhythmic agents but may
      resolve during long-term follow-up.

PMID- 7732990
TI  - Coronary vascular reactivity is abnormal in patients with Chagas' heart disease.
AB  - Symptoms of myocardial ischemia, such as chest pain (sometimes with anginal
      features), acute myocardial infarction, and segmental wall motion abnormalities
      (including left ventricular apical aneurysm), frequently occur in patients with
      Chagas' heart disease. Because these clinical findings occur in the presence of
      normal coronary arteries, it is possible that an abnormality of the coronary
      vascular reactivity could be present in these patients. Therefore the current
      study was undertaken to determine whether endothelium-dependent coronary
      vasodilation is abnormal in Chagas' heart disease. Coronary endothelial function
      was assessed by infusing the endothelium-dependent vasodilator acetylcholine (10(
      8) to 10(-6) mol/L) and the endothelium-independent vasodilator adenosine (10(-4)
      mol/L) into the left anterior descending coronary artery of nine patients (age 43
      +/- 4 years) with Chagas' heart disease. Coronary blood flow was measured with a
      Doppler flow velocity catheter and by quantitative coronary cineangiography. The
      left ventricular ejection fraction was 39% +/- 5%; eight patients had a left
      ventricular apical aneurysm; and one had an area of anteroapical hypokinesis. An
      impairment of the endothelium-dependent coronary vasodilation was demonstrated by
      a reduction in coronary blood flow of 41.2% +/- 12.8% produced by the infusion of
      acetylcholine at 10(-6) mol/L and by a blunted but preserved increase in coronary
      blood flow of 114.6% +/- 65.0% with the infusion of adenosine at 10(-4) mol/L (p
      = 0.03). In conclusion, patients with Chagas' heart disease have an abnormality
      of the coronary endothelium-dependent vasodilation, and this abnormality may play
      a role in their chest pain syndrome and in the development of segmental wall
      motion abnormalities.

PMID- 7732991
TI  - Long-term prognostic value of exercise testing in men and women from the Coronary
      Artery Surgery Study (CASS) registry.
AB  - Many prior studies involving a predominantly male population have demonstrated
      the importance of exercise test results in determining the outcome of patients
      with coronary artery disease. The prognostic significance of exercise testing in
      women is unknown. In our study, a total of 3,086 men and 747 women underwent
      maximal treadmill exercise testing, coronary angiography, and were prospectively
      followed for up to 16 years. They were divided into 3 groups (high, intermediate,
      and low risk) on the basis of exercise testing. Sixteen-year survival based on
      exercise test groups ranged from 38% to 61% in men and from 44% to 79% in women
      (p < 0.001). Among men, 12-year survival was enhanced by coronary artery bypass
      surgery versus medical therapy in the high-risk subgroup (69% vs 55%,
      respectively, p = 0.0025), but the 2 therapies were similar in the intermediate-
      and low-risk subgroups. Among women, neither medical nor surgical therapy
      resulted in improved 12-year survival rates in any of the 3 subgroups. These
      results suggest that exercise testing is helpful in assessing long-term survival
      in men and women. However, only exercise testing in men could identify a high
      risk subset whose survival was enhanced by coronary artery bypass graft surgery.

PMID- 7732992
TI  - Significance of a coronary artery with thrombolysis in myocardial infarction
      grade 2 flow "patency" (outcome in the thrombolysis and angioplasty in myocardial
      infarction trials). Thrombolysis and Angioplasty in Myocardial Infarction Study
      Group.
AB  - To determine whether pharmacologic reperfusion to Thrombolysis in Myocardial
      Infarction (TIMI) grade 2 flow during acute myocardial infarction confers the
      same clinical benefit as restoration of TIMI 3 flow, in-hospital clinical and
      angiographic outcomes in 1,229 patients prospectively enrolled in the
      Thrombolysis and Angioplasty in Myocardial Infarction trials were analyzed.
      Patients were treated with intravenous tissue plasminogen activator or urokinase,
      or both. Angiography of the infarct-related artery 90 minutes after initiation of
      thrombolytic therapy demonstrated TIMI grades 0, 1, 2, or 3 flow in 20%, 7%, 17%,
      and 55% of vessels, respectively. Rescue or adjunctive coronary angioplasty was
      performed in 80%, 27%, and 16% of patients with TIMI 0/1, 2, or 3 flow,
      respectively. Predischarge angiography was performed in 963 patients. A
      significant gradient of increasing mortality was seen in patients with lower TIMI
      flow (4.3%, 6.1%, and 10.1% with TIMI 3, 2, and 0/1 flow, respectively, p =
      0.002). The incidence of congestive heart failure and recurrent ischemia was
      significantly higher in patients with TIMI 2 than with TIMI 3 perfusion (26% vs
      19% for heart failure, p = 0.03; 23% vs 17% for recurrent ischemia, p = 0.05).
      Acute left ventricular ejection fraction and infarct zone regional wall motion
      were also significantly improved in patients with TIMI 3 than with TIMI 2 flow,
      with trends toward better improvement in global and regional function in the TIMI
      3 group. These findings were not affected by the use of acute coronary
      angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732993
TI  - Heart rate variability during repeated arterial occlusion in coronary
      angioplasty.
AB  - Acute coronary occlusion may cause severe autonomic reactions that can modify the
      clinical presentation of acute ischemic events. To evaluate whether adaptation in
      these autonomic reactions exists during repeated short coronary occlusions, heart
      rate (HR) and its variability in the time and frequency domains were analyzed in
      70 patients with significant (50% to 95%) coronary artery stenosis immediately
      before and during 2 identical balloon occlusions of the vessel (mean 110
      seconds). Reactions were compared with the range of nonspecific changes formed by
      analyzing a control group (n = 13) with no ischemia during balloon inflation in a
      totally occluded coronary artery. Thus, neither occlusion caused significant
      changes in HR or HR variability in 29 patients (41%). Vagal activation, as seen
      by an abnormal increase in HR variability or bradycardia, or both, was observed
      in 24 patients (34%). HR reactions in this group (p < 0.05) were significantly
      attenuated during the second occlusion. An opposite reaction (i.e., abnormal
      decrease in HR variability or tachycardia, or both) was observed in 17 patients
      (24%). A nonsignificant tendency for attenuation of the reactions was also seen
      in this group. Severity of chest pain, frequency of ST-segment shifts, or
      narrowing of pulse pressure were comparable during the 2 occlusions. Thus, a
      preceding short vessel occlusion-reperfusion cycle seems to attenuate autonomic
      HR reactions, especially vagal reactions, during subsequent coronary occlusion.
      Alleviation of extreme autonomic reactions may modify the clinical outcome of
      coronary occlusion in a beneficial way.

PMID- 7732994
TI  - Decreased heart rate variability in men with phobic anxiety (data from the
      Normative Aging Study).
AB  - Prospective cohort studies suggest that phobic anxiety is a strong risk factor
      for fatal coronary artery disease, in particular, sudden cardiac death. It has
      also been established that reduced heart rate (HR) variability can identify
      patients at high risk for subsequent sudden cardiac death. We therefore
      hypothesized that persons with symptoms of phobic anxiety may exhibit reduced HR
      variability. We tested our hypothesis in 581 men, aged 47 to 86 years, enrolled
      in the Normative Aging Study who were free of coronary artery disease and
      diabetes. Symptoms of anxiety were assessed using the Crown-Crisp index, an
      instrument that has been demonstrated in previous prospective studies to strongly
      predict risk of sudden cardiac death. HR variability was measured under
      standardized conditions, with paced deep breathing (6 breaths/1 min). Two
      measures of HR variability were used: the SD of HR and the maximal minus minimal
      HR over 1 minute. Men reporting higher levels of phobic anxiety had a higher
      resting HR (p = 0.025 for linear trend). After adjusting for age, mean HR, and
      body mass index in analyses of covariance, men reporting higher levels of phobic
      anxiety had lower HR variability, whether measured by the SD of HR (p = 0.03 for
      linear trend). These data suggest that phobic anxiety is associated with altered
      cardiac autonomic control, and hence increased risk of sudden cardiac death.

PMID- 7732995
TI  - Predictors of groin complications after balloon and new-device coronary
      intervention.
AB  - We reviewed the clinical course of 5,042 patients who underwent percutaneous
      transluminal coronary angioplasty (PTCA) using balloons or new devices: (stent,
      laser, directional and rotational atherectomy). A vascular complication was
      defined as the formation of a groin hematoma, bleeding, pseudoaneurysm, fistula,
      or the need for surgical repair. Vascular complications occurred in 309 (6.1%)
      patients, and 117 (2.3%) required vascular repair; among these patients, surgery
      was performed for correction of an an arteriovenous fistula in 12%, repair of
      pseudoaneurysm in 72%, repair for expanding hematoma and femoral artery
      lacerations in 10%, and retroperitoneal bleeding in 6%. The correlates of
      vascular complications were older age (66.8 vs 62.1 years; p < 0.0001), female
      gender (43% vs 26%; p < 0.0001), increased weight (82.1 +/- 16.46 vs 78.0 +/-
      16.6 kg; p < 0.001), higher systolic blood pressure (140 +/- 25 vs 134 +/- 20 mm
      Hg; p < 0.001), increased heparin dose during the procedure (14,352 +/- 3,879 vs
      13,599 +/- 3,508 IU; p = 0.001), administration of heparin after the procedure
      (232 vs 2,985 patients; p < 0.0001) and intracoronary stenting (14.9% vs 3.5%; p
      < 0.0001). Fifteen patients of 214 (7.0%) who underwent stent implantation had
      surgical repair. Vascular complications were not related to the size of the
      arterial sheath (8.11 +/- 0.8 vs 8.8 +/- 0.7Fr; p = 0.11) and the use of devices
      other than stents (laser, atherectomy) did not increase the rate of vascular
      complications.

PMID- 7732996
TI  - Comparison of outcome of cardiac rehabilitation in black women and white women.
AB  - Coronary artery disease is the leading cause of death among black women in the
      United States. Black women also demonstrate a greater prevalence of coronary risk
      factors and a higher mortality after myocardial infarction than white women. To
      evaluate the clinical profile and outcome of black women in an urban-based
      cardiac rehabilitation program, 35 black women (aged 54 +/- 13 years) and 47
      white women (aged 57 +/- 10 years) were prospectively studied. Black women had
      similar admitting diagnoses as white women, with recent myocardial infarction
      being the most common (37%). Coronary risk factors were more prevalent in black
      women than white women in the program: hypertension (71% vs 53%; p = 0.09)
      diabetes mellitus (46% vs 26%; p = 0.06), obesity (74% vs 49%; p < 0.05).
      Cholesterol and high-density lipoprotein levels were similarly elevated in black
      (251 +/- 53 mg/dl) and in white (248 +/- 52 mg/dl) women, whereas 34% of black
      and 21% of white women were active smokers. There was no significant difference
      in initial exercise capacity at program entry. Fewer black women (51%) completed
      the 12-week program than white women (64%), p = NS. Comparison of initial and
      follow-up exercise tests after 12 weeks of moderate to high-intensity dynamic
      exercise demonstrated significant and similar improvements in functional capacity
      in both black (4.2 +/- 1.6 vs 5.6 +/- 1.7 METs; p < 0.001) and white (4.8 +/- 2.2
      vs 5.7 +/- 2.2 METs; p < 0.01) women. Among obese patients, only the white women
      lost weight.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732997
TI  - Effect of intensive diabetes management on macrovascular events and risk factors
      in the Diabetes Control and Complications Trial.
AB  - The Diabetes Control and Complications Trial (DCCT), a multicenter, randomized,
      controlled clinical trial, demonstrated that intensive diabetes therapy delays
      the onset and slows the progression of retinopathy, nephropathy, and neuropathy
      in patients with insulin-dependent diabetes mellitus. This study presents the
      effect of intensive therapy on atherosclerosis-related events and associated risk
      factors. Patients (n = 1,441) between the ages of 13 and 39 years with insulin
      dependent diabetes mellitus were randomly assigned to conventional or intensive
      diabetes treatment. The patients were free of cardiovascular disease at baseline.
      Patients with hypertension, hypercholesterolemia, or obesity were excluded.
      Average length of follow-up was 6.5 years (range 3.5 to 9). The study used
      standardized definitions of macrovascular events, verification of such events,
      and central laboratories for determination of lipids and the grading of
      electrocardiograms. The number of combined major macrovascular events was almost
      twice as high in the conventionally treated group (40 events) as in the intensive
      treatment group (23 events), although the differences were not statistically
      significant (p = 0.08). There were no differences in the cumulative incidence of
      hypertension. Mean total serum cholesterol, calculated low-density lipoprotein
      cholesterol, and triglycerides were significantly reduced in the intensive
      treatment group (p < or = 0.01), as was the development of low-density
      lipoprotein cholesterol levels > 160 mg/dl. Weight gain was significantly
      increased in the intensive-treatment group (p < 0.001). There were no differences
      in cigarette smoking habits, consumption of alcohol, or aspirin use between
      treatment groups. The reduction in some, but not all, cardiovascular risk factors
      suggests a potential beneficial effect of intensive therapy on macrovascular
      disease in insulin-dependent diabetes mellitus.

PMID- 7732998
TI  - Cardiac output in single-lead VDD pacing versus rate-matched VVIR pacing.
AB  - The importance of atrioventricular synchronous pacing compared with single
      chamber rate-responsive pacing is still under discussion, especially for low
      intensity workload representing daily life activities. We evaluated hemodynamics
      in single-lead VDD pacing versus VVIR pacing in 11 patients (8 men and 3 women,
      aged 58.6 +/- 13.8 years) with normal left ventricular function and a previously
      implanted single-lead VDDR pacemaker. A low-intensity steady-state treadmill test
      at 1 to 2.5 mph with a gradient of 2% to 4% was performed. Cardiac output was
      determined using a standard carbon dioxide rebreathing technique. Initially, the
      VDD mode was programmed, and after 5 minutes of exercise, cardiac output was
      measured in steady-state conditions. The pacemaker was then reprogrammed to the
      VVI mode at a rate 5 to 10 beats above the maximal atrial tracking rate to
      simulate rate-matched VVIR pacing (VVIRm). After 5 additional minutes of steady
      state exercise, cardiac output was measured again. The maximal atrial rate in the
      VDD mode was 119 +/- 19 beats/min versus a programmed rate of 129 +/- 18
      beats/min in the VVIRm mode. VDD pacing resulted in a significantly higher
      cardiac output than VVIRm pacing (10.6 +/- 1.9 vs 9.2 +/- 1.4 L/min; p < 0.002),
      with a mean difference of 1.6 +/- 1.2 L/min between the 2 modes. In the VDD mode,
      stroke volume (90.7 +/- 20.1 vs 71.6 +/- 13.0 ml; p < 0.001) and maximal oxygen
      uptake (1,183 +/- 264 vs 1,076 +/- 289 ml/min, p < 0.01) were also higher than in
      VVIRm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7732999
TI  - Safety of implantation of a cardioverter-defibrillator without general anesthesia
      in an electrophysiology laboratory.
AB  - Implantable cardioverter-defibrillators (ICDs) have conventionally been implanted
      in an operating room under general anesthesia. This study was performed to
      evaluate ICD implantation without general anesthesia by 2 electrophysiologists in
      an electrophysiology laboratory. Between February and September 1994, 27
      consecutive patients (22 men and 5 women, mean age 59 +/- 15 years) who underwent
      ICD implantation by 2 electrophysiologists were included in this study. Fourteen
      patients received biphasic waveform ICDs, and the remaining 13 had monophasic
      waveform devices. All patients received local anesthesia and intravenous sedation
      for implantation. Implantation was successful in 23 of 27 patients at first
      attempt (11 of 11 with biphasic and 12 of 16 with monophasic waveform ICDs,
      respectively). Of 4 patients in whom implantation was initially unsuccessful, 3
      subsequently received biphasic devices and 1 had improved defibrillation
      threshold ( < or = 26 J) on repeat testing after amiodarone withdrawal. Mean
      implantation time was 128 +/- 51 minutes, with 132 +/- 35 minutes under sedation.
      Patients who received biphasic versus monophasic waveform ICDs had no significant
      differences in mean sedation or implantation time. Minor complications occurred
      in 2 patients (7%): 1 minor abdominal pocket hematoma and 1 incision-site
      cellulitis. Mean time from implantation to discharge was 2.5 +/- 2.1 days. During
      late follow-up (n = 23; mean 12.4 +/- 5.8 weeks), all devices were functioning
      appropriately. In conclusion, this report demonstrates that ICD implantation can
      be successfully and safely performed by a team of 2 electrophysiologists using
      local anesthesia and intravenous sedation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733000
TI  - Measuring extracellular matrix turnover in the serum of patients with idiopathic
      or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis.
AB  - Circulating levels of extracellular matrix components were measured by
      radioimmunoassays and tested if they were useful for clinical staging in chronic
      heart failure. In 41 patients with dilated cardiomyopathy (33 idiopathic and 8
      ischemic cases), the serum concentrations of procollagen type III aminoterminal
      peptide (PIIINP), type I collagen telopeptide (ICTP), and basement membrane
      laminin were significantly higher than in 30 healthy controls regardless of the
      underlying etiology. Patients with serum values of PIIINP, ICTP, and laminin > 7
      micrograms/L, 7.6 micrograms/L, and 2.3 U/ml, respectively, were at higher
      relative risk for advanced clinical stage, poor hemodynamic condition,
      hyponatremia, heart transplantation, and death during follow-up than patients
      with low levels, with the exception that serum laminin > 2.3 U/ml was not
      significantly associated with hyponatremia and heart transplantation. Despite
      their interdependence on liver function, circulating levels of PIIINP and ICTP
      were independent predictors of mortality. In 17 of the 41 patients with
      cardiomyopathy whose explanted hearts were available for histologic evaluation,
      serum PIIINP, ICTP, and laminin significantly correlated with the myocardial area
      fractions of their tissue analogues (PIIINP vs myocardial collagen type III, r =
      0.784, p = 0.0013; serum ICTP vs myocardial collagen type I, r = 0.603, p =
      0.0527; and serum laminin vs myocardial laminin, r = 0.605, p = 0.0411). In
      conclusion, the increase in extracellular matrix turnover, which may partially be
      derived from fibrosis in the myocardium, can be measured in the serum of patients
      with dilated cardiomyopathy, and has an impact on risk stratification and
      prognosis.

PMID- 7733001
TI  - Results of atrioventricular synchronous pacing with optimized delay in patients
      with severe congestive heart failure.
AB  - To verify that atrioventricular (AV) synchronous pacing (DDD) with short AV delay
      improves the condition of patients with severe congestive heart failure, we
      implanted DDD pacemakers in 10 patients with severe heart failure (New York Heart
      Association [NYHA] class III to IV). One day after pacemaker implantation, the AV
      delay was optimized by Doppler echocardiographic measurements over the aortic
      outflow tract. Patients were evaluated regarding NYHA class, stroke volume,
      cardiac output, ejection fraction, and quality of life at 1, 3, and 6 months
      after pacemaker implantation. Although the optimized AV delay was associated with
      short-term improvement in stroke volume and cardiac output (baseline stroke
      volume = 22 +/- 7 ml, day 1 = 28 +/- 12 ml; p = 0.03: baseline cardiac output =
      1.9 +/- 0.6 L/min, day 1 = 2.2 +/- 1.1 L/min; p = 0.10), the mean stroke volume,
      cardiac output, NYHA class, and ejection fraction did not change significantly
      after 1, 3, and 6 months of pacing compared with baseline values. Three patients
      improved in NYHA class during the follow-up. A consistent improvement in stroke
      volume, cardiac output, NYHA class, and ejection fraction was observed in only 1
      patient. In conclusion, we found no beneficial effects of AV-synchronous pacing
      with optimized AV delay in patients with severe heart failure.

PMID- 7733002
TI  - Effect of aspirin on spontaneous contrast in the brachial veins of normal
      subjects.
AB  - Blood cell aggregates are thought to be the cause of spontaneous echo contrast
      (SEC), although there is disagreement as to whether red cell or platelet
      aggregates produce this effect. One way to differentiate between these 2
      possibilities is to evaluate the effect of aspirin on SEC because aspirin would
      not be expected to affect red cell aggregates. To eliminate the need to perform
      repetitive transesophageal echocardiographic studies, and the possible effect of
      the underlying disease process on SEC, the effect of aspirin on SEC in the
      brachial vein was studied in normal volunteers using a single-blind, before-and
      after study design. Other factors known to affect blood echogenicity including
      hematocrit, sedimentation rate, and the presence of platelet aggregates by
      microscopy were also studied. The amount of SEC was quantitated by image analysis
      and expressed as the aggregate score. The results in 10 volunteers showed that
      all had SEC in brachial veins before aspirin, but there was no significant day-to
      day variation in the amount of SEC during the control period (mean +/- SEM
      104,248 +/- 23,088, 153,722 +/- 35,664, and 124,568 +/- 22,827 for days 1, 3, and
      5, respectively). A significant decrease in the aggregate score occurred after 7
      days of aspirin, 650 mg twice a day (51,690 vs 127,513, p = 0.002); this was
      accompanied by a striking decrement in the size of the largest platelet aggregate
      found in venous blood. Aspirin caused no significant change in the hematocrit or
      sedimentation rate. These results indicate that there is a component of SEC that
      is aspirin-sensitive and is likely to represent platelet aggregates.

PMID- 7733003
TI  - Artificial neural networks for recognition of electrocardiographic lead reversal.
AB  - Misplacement of electrodes during the recording of an electrocardiogram (ECG) can
      cause an incorrect interpretation, misdiagnosis, and subsequent lack of proper
      treatment. The purpose of this study was twofold: (1) to develop artificial
      neural networks that yield peak sensitivity for the recognition of right/left arm
      lead reversal at a very high specificity; and (2) to compare the performances of
      the networks with those of 2 widely used rule-based interpretation programs. The
      study was based on 11,009 ECGs recorded in patients at an emergency department
      using computerized electrocardiographs. Each of the ECGs was used to
      computationally generate an ECG with right/left arm lead reversal. Neural
      networks were trained to detect ECGs with right/left arm lead reversal. Different
      networks and rule-based criteria were used depending on the presence or absence
      of P waves. The networks and the criteria all showed a very high specificity
      (99.87% to 100%). The neural networks performed better than the rule-based
      criteria, both when P waves were present (sensitivity 99.1%) or absent
      (sensitivity 94.5%). The corresponding sensitivities for the best criteria were
      93.9% and 39.3%, respectively. An estimated 300 million ECGs are recorded
      annually in the world. The majority of these recordings are performed using
      computerized electrocardiographs, which include algorithms for detection of
      right/left arm lead reversals. In this study, neural networks performed better
      than conventional algorithms and the differences in sensitivity could result in
      100,000 to 400,000 right/left arm lead reversals being detected by networks but
      not by conventional interpretation programs.

PMID- 7733004
TI  - Long-term prognosis of patients with a normal exercise echocardiogram and
      clinical suspicion of myocardial ischemia.

PMID- 7733005
TI  - Effect of serum lipid concentrations on restenosis after successful de novo
      percutaneous transluminal coronary angioplasty in patients with total cholesterol
      160 to 240 mg/dl and triglycerides < 350 mg/dl.

PMID- 7733006
TI  - Quantitative assessment of coronary arterial diameter before and after balloon
      angioplasty of severe stenoses.

PMID- 7733007
TI  - Limitations of estimating metabolic equivalents in exercise assessment in
      patients with coronary artery disease.

PMID- 7733008
TI  - Precordial ST change and site of the infarct-related lesion in right coronary
      artery-related inferior wall acute myocardial infarction.

PMID- 7733009
TI  - Relation of left atrial appendage function to the duration and reversibility of
      nonvalvular atrial fibrillation.

PMID- 7733010
TI  - Does complexity theory apply to the conduction ratios occurring during
      progression of stable atrial flutter with 2:1 into 4:1 atrioventricular block?

PMID- 7733011
TI  - Calculation of QTc duration and variability in the presence of sinus arrhythmia.

PMID- 7733012
TI  - Usefulness of adenosine in diagnosis of tachyarrhythmias.

PMID- 7733013
TI  - Can patients with neuromediated syncope safely drive motor vehicles?

PMID- 7733014
TI  - Effects of obesity on QT, RR, and QTc intervals.

PMID- 7733015
TI  - Balloon valvotomy for mitral stenosis associated with moderate mitral
      regurgitation.

PMID- 7733016
TI  - Comparison of the Bruce and ramp protocols in the assessment of left ventricular
      performance during exercise in healthy women.

PMID- 7733017
TI  - Racial difference in incidence of cough with angiotensin-converting enzyme
      inhibitors (a tale of two cities).

PMID- 7733018
TI  - Orthotopic heart transplantation in patients with treated malignancies.

PMID- 7733019
TI  - Hepatic vein velocities in children with right ventricular hypertension.

PMID- 7733020
TI  - Reproducibility of the measurement of coronary calcium with ultrafast computed
      tomography.

PMID- 7733021
TI  - Thermic effect of food in humans: methods and results from use of a respiratory
      chamber.
AB  - During the past two decades, many investigators have measured the thermic effect
      of food (TEF) in humans and have speculated on its role in the development of
      obesity. In this study we compared different ways of computing TEF from daily
      energy expenditure measurements in a respiratory chamber, evaluated the
      determinants of TEF, and more importantly assessed for the first time the
      relation between TEF and change in body weight. In 471 subjects, TEF was 1697 +/-
      857 kJ/d (mean +/- SD), ie, 18 +/- 9% of energy intake. In 114 subjects studied
      more than once, intraindividual TEF variability was very high (CV = 48%). TEF
      correlated positively with the level of spontaneous physical activity (SPA) and
      negatively with fasting plasma glucose and insulin concentrations. TEF correlated
      inversely with age (males only) and body weight, percent body fat, and waist-to
      hip ratio (females only). The level of SPA and fasting plasma glucose
      concentration were the only significant determinants of TEF, explaining 15% of
      its variance. In 137 subjects in whom body weight was measured > or = 6 mo after
      TEF measurement (mean follow-up duration of 2.9 +/- 1.7 y), a low TEF was not
      predictive of body weight gain. We conclude that, despite the low reproducibility
      of TEF from use of a respiratory chamber, data in a large number of subjects
      suggest that TEF is increased by higher SPAs and that insulin resistance is
      associated with a low TEF. More important, longitudinal data indicate that the
      variability in TEF is not associated with changes in body weight.

PMID- 7733022
TI  - Fluoxetine increases resting energy expenditure and basal body temperature in
      humans.
AB  - Humans lose weight when administered fluoxetine, an inhibitor of serotonin
      reuptake by nerve terminals. To determine whether increased energy expenditure
      contributes to this weight loss we admitted 20 nondepressed obese women to a
      metabolic unit where they were randomly assigned to 3 wk of a 1.76-MJ/d formula
      diet and either 60 mg fluoxetine/d or a placebo. Resting energy expenditure of
      the control subjects fell below normal after 5.6 +/- 0.6 d of energy restriction,
      whereas that of the fluoxetine-treated subjects increased by 4.4 +/- 1.8% (P <
      0.005) within 3 d of commencing treatment. This increased resting energy
      expenditure then reversed and fell below normal after 9.8 +/- 0.9 d of energy
      restriction. Basal body temperature of the control subjects decreased
      insignificantly during the period of energy restriction, but that of the
      fluoxetine-treated subjects increased by 0.28 +/- 0.10 degrees C (P < 0.05)
      within 3 d of commencing diet and drug treatment. Urinary norepinephrine
      excretion and the serum triiodothyronine concentration decreased equally in both
      groups. Despite identical energy intakes and equal nitrogen balance, the
      fluoxetine-treated subjects lost weight faster than the control subjects during
      the final week of energy restriction (P < 0.05). We propose that serotonin
      reuptake inhibition increases energy expenditure by increasing basal body
      temperature.

PMID- 7733023
TI  - Parental body composition and infant energy expenditure.
AB  - It has been suggested that infants born to overweight parents are at risk of
      becoming overweight because of reduced total energy expenditure (TEE). We
      therefore examined the relationship between infant TEE and parental nutritional
      status as assessed by body mass index (BMI) in a large sample of healthy infants.
      TEE was measured by the doubly labeled water method in 124 infants at 12 wk of
      age. Sleeping metabolic rate (SMR) was measured by indirect calorimetry in 70 of
      these infants. Indexes of physical activity were calculated as TEE/SMR and TEE
      SMR. No aspect of infant energy expenditure was found to be related to parental
      BMI. Moreover, there was no difference between TEE of two subsets of infants born
      to parents with high and low BMIs. We therefore find no evidence for parental
      body composition being associated with reduced infant energy expenditure at 12 wk
      of age.

PMID- 7733024
TI  - Zinc supplementation during lactation: effects on maternal status and milk zinc
      concentrations.
AB  - The effects of a zinc supplement on maternal zinc status and milk zinc
      concentrations through > or = 7 mo of lactation were examined. Seventy-one
      lactating women received either a daily 15-mg zinc supplement (ZS, n = 40) or
      placebo (NZS, n = 31) started by 2 wk postpartum in a double-blind, randomized
      design. Overall mean zinc intakes were 13.0 +/- 3.4 mg/d for the NZS group and
      25.7 +/- 3.9 mg/d (including supplement) for the ZS group. Plasma zinc
      concentrations of the ZS group were significantly higher than those of the NZS
      group (P = 0.05). Milk zinc concentrations declined significantly over the course
      of the study for all subjects but were not affected by zinc supplementation. The
      mean dietary zinc intake observed in the nonsupplemented group was adequate to
      maintain normal maternal zinc status and milk zinc concentrations through > or =
      7 mo lactation. Similar controlled intervention trials in less well-nourished
      populations will be required to assess the impact of lower zinc intakes on milk
      zinc concentrations.

PMID- 7733025
TI  - Feeding premature newborn infants palmitic acid in amounts and stereoisomeric
      position similar to that of human milk: effects on fat and mineral balance.
AB  - The effect of the structure of human milk triglycerides on intestinal fat
      absorption remains controversial. Twelve infants were each fed, for 1 wk in a
      crossover design, two formulas that differed only in triglyceride configuration.
      The "beta" formula contained triglycerides similar to those in human milk (26%
      palmitic acid, esterified predominantly to the sn-2 position) whereas in the
      "alpha" formula, which contained triglycerides similar to those in formulas
      currently marketed, palmitate was mainly at the sn-1,3 positions. Fatty acid,
      fat, and mineral balances were measured at the end of each 1-wk period. Myristic,
      palmitic, and stearic acids were absorbed better from the beta formula, but total
      fat excretion was not reduced. During the feeding of beta formula fecal calcium
      excretion was lower, urinary calcium higher, and urinary phosphate lower. A
      formula containing triglycerides similar to those in human milk has significant
      effects on fatty acid intestinal absorption and improves mineral balance in
      comparison with a conventional formula.

PMID- 7733026
TI  - Comparison of palmolein and olive oil: effects on plasma lipids and vitamin E in
      young adults.
AB  - Twenty-one healthy normocholesterolemic young adults, men and women, completed a
      randomized 30-d/30-d crossover comparison of the effect of palmolein and olive
      oil on plasma lipids. The subjects were free-living volunteers who changed to low
      fat diets to which one of the test oils was added (used as a spread, for baking,
      or for frying) in turn. Complete food records were kept throughout: the test oils
      were compared at 17% of total dietary energy. Under the conditions of this
      experiment plasma total and low-density-lipoprotein (LDL) cholesterol were almost
      identical with the two oils, so that when the palmitic acid (16:0) in palm oil
      replaced oleic acid (18:1) in olive oil the expected increase in LDL cholesterol
      was not seen. These results indicate that 16:0, though saturated, is not always a
      plasma cholesterol-raising fatty acid. Palmolein is rich in vitamin E, alpha
      tocopherol, and especially tocotrienols, but the latter were barely detectable in
      plasma.

PMID- 7733027
TI  - Increasing the dietary polyunsaturated fat content alters whole-body utilization
      of 16:0 and 10:0.
AB  - Six healthy adult males were fed four different diets to determine the effects of
      the quantity of fat (30% or 40% of energy as fat) and type of fat
      (polyunsaturated or saturated) on utilization of fatty acids. Each diet was fed
      for 15 d. The ratio of dietary polyunsaturated to saturated fat (P:S) was
      formulated at either 0.2 or 1.0 at both fat intakes. Subjects provided breath
      tests to measure background 13C and response to [1-13C]10:0 and [1-13C]16:0 fed
      with a test meal. Increasing the P:S increased whole-body oxidation of labeled
      10:0 by 30% after consumption of both low- and high-fat diets. When labeled 16:0
      was fed, the amount of 13C excreted in breath increased by a factor of 2.4 after
      the low-fat diet with a high P:S compared with the diet with a low P:S. The
      results suggest that the amount and type of fat in the diet affect utilization of
      individual fatty acids in normal subjects.

PMID- 7733028
TI  - Increased plasma bicarbonate and growth hormone after an oral glutamine load.
AB  - An oral glutamine load was administered to nine healthy subjects to determine the
      effect on plasma glutamine, bicarbonate, and circulating growth hormone
      concentrations. Two grams glutamine were dissolved in a cola drink and ingested
      over a 20-min period 45 min after a light breakfast. Forearm venous blood samples
      were obtained at zero time and at 30-min intervals for 90 min and compared with
      time controls obtained 1 wk earlier. Eight of nine subjects responded to the oral
      glutamine load with an increase in plasma glutamine at 30 and 60 min before
      returning to the control value at 90 min. Ninety minutes after the glutamine
      administration load both plasma bicarbonate concentration and circulating plasma
      growth hormone concentration were elevated. These findings demonstrate that a
      surprisingly small oral glutamine load is capable of elevating alkaline reserves
      as well as plasma growth hormone.

PMID- 7733029
TI  - Whole-body protein turnover in response to hyperinsulinemia in humans
      postabsorptively with [15N]glycine as tracer.
AB  - Studies using stable isotopes to determine the effect of insulin on whole-body
      protein turnover have given conflicting results. The precursor approach to
      studying healthy subjects in a postabsorptive state shows reductions in breakdown
      and oxidation; with end product methods in parenterally fed patients no such
      changes are seen. To explain these discrepancies, we measured protein turnover
      with and without euglycemic hyperinsulinemic clamping postabsorptively in nine
      healthy subjects by using single-dose [15N]glycine with calculations based on
      ammonia and urea end product excretion. With and without clamping, respectively,
      insulin reduced nitrogen (22.1 and 48.2 mg.kg-1.9 h-1, P < 0.01) and urea (15.8
      and 37.5 mg.kg-1.9 h-1, P < 0.05) but increased ammonia (7.7 and 5.0 mg.kg-1.9 h
      1, P < 0.05) excretion. Although the urea end product method suggested that
      insulin tended to reduce both protein breakdown and synthesis, the protein
      metabolism changes detected with the ammonia end product method tended to be in
      the opposite direction. The [15N]glycine ammonia end-product method may be
      inappropriate for studies during insulin infusion because of insulin's effect on
      ammonia excretion.

PMID- 7733030
TI  - L-cysteine and glutathione metabolism are impaired in premature infants due to
      cystathionase deficiency.
AB  - There are conflicting reports in the literature as to whether L-cysteine is an
      essential amino acid in premature infants as the result of the absence of hepatic
      cystathionase activity. To analyze the physiological importance of the
      cystathionase deficiency, we studied sulfur amino acid metabolism in human
      neonates of different gestational ages. Plasma cystathionine concentrations are
      higher in premature infants < or = 32 wk gestation (group 1) than in premature
      infants of 33-36 wk gestational age (group 2) or in full-term infants (group 3),
      whereas plasma cysteine concentrations are much lower in group 1 and 2 premature
      infants than in mature infants. Furthermore, erythrocytes from group 1 premature
      infants synthetize glutathione from L-methionine (a process dependent on the
      cystathionase pathway) at a much lower rate than do erythrocytes from group 2
      premature or full-term infants. Thus, the metabolic flow through the
      transsulfuration pathway may be insufficient to meet the glutathione and cysteine
      requirements of very premature infants.

PMID- 7733031
TI  - The effect of raw potato starch on energy expenditure and substrate oxidation.
AB  - Because resistant starch (RS) is not absorbed as glucose in the small intestine
      of healthy humans, postprandial thermogenesis should be lower after the intake of
      RS as compared with digestible starch. To evaluate this hypothesis, we measured 5
      h postprandial thermogenesis and substrate oxidation by indirect calorimetry
      after ingestion of 50 g pregelatinized (0% RS) and 50 g raw potato starch (54%
      type II RS) in 15 healthy, normal-weight young males. The subjects consumed each
      starch (mixed in diluted fruit syrup) twice on separate days and in random order.
      RS intake was followed by lower thermogenesis (46.5 +/- 13.1 compared with 115.4
      +/- 10.4 kJ/5 h; P = 0.008), lower glucose oxidation (P < 0.0005), and greater
      fat oxidation (P = 0.013) than was pregelatinized starch consumption. Our results
      suggest that RS has no thermogenic effect and that its presence does not
      influence the size of the thermic response to digestible starch.

PMID- 7733032
TI  - Pupillary and visual thresholds in young children as an index of population
      vitamin A status.
AB  - A prototype scotopic sensitivity machine was used to evaluate pupillary and
      visual thresholds for 295 Indonesian children aged 1-5 y, most of whom were
      initially vitamin A-deficient. Subjects were tested 6 and 9 mo after receiving a
      high dose of vitamin A. A group of 136 older children was tested at 6 mo after
      dosing; all subjects underwent testing at 9 mo. After testing at 9 mo, children
      randomly received either a second high dose of vitamin A or placebo and were
      tested a final time 2 wk later. Children with abnormal pupillary thresholds had
      significantly higher relative dose responses (RDRs) (P < 0.01) and significantly
      lower serum retinol values (P = 0.05) than did normal children. The mean
      pupillary threshold rose (eg, retinal sensitivity fell) as vitamin A status
      deteriorated between 6 and 9 mo after initial dosing, and was significantly
      different from a group of normal American children tested previously (P < 0.001).
      After placebo-controlled dosing, the decline in pupillary and visual thresholds
      (rise in retinal sensitivity) was significant for children receiving vitamin A
      but not for children receiving placebo.

PMID- 7733033
TI  - Moderate folate deficiency does not cause global hypomethylation of hepatic and
      colonic DNA or c-myc-specific hypomethylation of colonic DNA in rats.
AB  - Global and gene-specific DNA hypomethylation is considered to be an important
      early epigenetic event in several human neoplasms. A growing body of evidence has
      suggested that DNA methylation can be altered by dietary manipulation of methyl
      group donors. This study investigated whether moderate depletion of folate, a
      dietary component needed for the synthesis of methyl groups, would cause
      decreased hepatic and colonic S-adenosylmethionine concentrations, and thereby
      lead to global and/or protooncogene-specific DNA hypomethylation. Weanling rats
      were fed an amino acid-defined diet containing either 0 or 8 mg folate/kg diet
      for 15 or 24 wk. Significantly lower systemic, hepatic and colonic folate
      concentrations were observed in the moderately folate-depleted rats than in
      controls at both 15 and 24 wk (P < 0.005). Although hepatic S-adenosylmethionine
      was significantly lower in the moderately folate-depleted rats than in controls
      at the two time points (P < 0.03), colonic S-adenosylmethionine concentrations
      were not significantly different between the two groups at either time point. No
      significant differences between the folate-depleted and control animals could be
      detected with regard to global DNA methylation in the liver or colonic mucosa.
      Furthermore, c-myc protooncogene-specific DNA methylation in the colonic mucosa
      was not significantly different between these two groups of animals. These
      results indicate that moderate folate depletion does not cause a significant
      reduction in global DNA methylation in liver or colonic mucosa or in c-myc
      specific colonic mucosal DNA methylation in this rat model.

PMID- 7733034
TI  - Vitamin B-6 requirement and status assessment: young women fed a depletion diet
      followed by a plant- or animal-protein diet with graded amounts of vitamin B-6.
AB  - The vitamin B-6 requirement of young women consuming a high-protein diet (1.55
      g/kg body wt) and the effect of protein quality on this requirement was studied.
      In addition, the response of clinical, functional, and biochemical measures of
      vitamin B-6 nutriture to short-term depletion and step-wise repletion of vitamin
      B-6 were evaluated. Eight healthy young women resided in a metabolic unit and
      were fed a formula depletion diet (< 0.05 mg vitamin B-6/d) for 11-28 d followed
      by either an animal-protein (AP) or plant-protein (PP) diet with successively
      increasing vitamin B-6 intakes (0.5, 1.0, 1.5, and 2.0 mg/d) for periods of 14-21
      d. Animal proteins were primarily from dairy and poultry sources and plant
      proteins were primarily from legumes. Vitamin B-6 status measures were assessed
      at weekly intervals. Results showed that a PP diet does not elevate the vitamin B
      6 requirement over that required for an AP diet given the high amount of dietary
      protein used in this study. It was also found that 0.015 mg vitamin B-6/g protein
      intake normalized most biochemical indexes of vitamin B-6 status (including those
      indicative of functional status), and that 0.020 mg/g protein normalized all
      biochemical measures except total urinary vitamin B-6. Adding a margin of safety
      to either the 0.015 or 0.020 mg/g protein intake would raise the vitamin B-6
      requirement for young women above the currently recommended dietary allowance of
      0.016 mg/g protein.

PMID- 7733035
TI  - Molybdenum absorption, excretion, and retention studied with stable isotopes in
      young men during depletion and repletion.
AB  - A study of molybdenum absorption, excretion, and balance was conducted in four
      young men fed a low-molybdenum diet (22 micrograms/d) for 102 d followed by 18 d
      of the same diet supplemented to contain 467 micrograms/d. The study was
      conducted to determine the minimum dietary molybdenum requirement of healthy
      young men. Stable isotopes of molybdenum were used as tracers. 100Mo was fed four
      times during the study, 97Mo was infused twice, and 94Mo was used as an isotopic
      diluent to quantify the molybdenum isotopes and total molybdenum in complete
      urine and fecal collections and in the diets. The study demonstrated that
      subjects could not consistently attain balance with the low-molybdenum diet, but
      balance improved with time, and no signs of molybdenum deficiency were observed.
      Molybdenum was very efficiently absorbed at both intakes of dietary molybdenum
      and urinary excretion increased as dietary molybdenum increased. Molybdenum
      turnover was significantly slower when dietary molybdenum was low. We estimate
      from these results that the minimum dietary molybdenum requirement is
      approximately 25 micrograms/d or possibly less. This suggests that the lower end
      of the recommended range could be less than the current recommended amount of 75
      micrograms/d.

PMID- 7733036
TI  - To what extent is bone mass determined by fat-free or fat mass?
AB  - One hundred sixty-four healthy black and white women aged 24-79 y were studied to
      determine to what extent bone mass is determined by fat-free mass (FFM). A
      multicomponent approach to body composition, with techniques that are not
      interdependent, was used. The measurements included dual x-ray absorptiometry
      (DXA), prompt gamma-neutron-activation analysis, inelastic neuron scattering,
      tritiated water dilution, and whole-body counting. Univariate correlations showed
      significant relationships of all the fat-free measures and most of the fat
      measures with bone mass measured by total body calcium (TBCa). Data from pre- and
      postmenopausal women were analyzed separately. The average FFM by itself
      explained 50-55% of the variability in TBCa whereas the average fat mass by
      itself explained only 5-18% of the variability. The contribution of fat mass was
      consistently greater in postmenopausal than in premenopausal women. When stepwise
      multiple regression with TBCa was performed to determine the influence of adding
      fat mass, height, and race to the relationship of FFM with TBCa, the variation
      explained by average FFM was 56% premenopausal, 50% postmenopausal; by height 3%
      premenopausal, 6% postmenopausal; by race 4% premenopausal, 8% postmenopausal;
      and average fat mass was not significant. Average values for fat mass and FFM
      were obtained by averaging all the methods used. In conclusion, in black and
      white healthy women, although bone mass may be partially influenced by fatness or
      race, the major determinant of bone mass is FFM. Fat mass may play a more
      important role in postmenopausal women.

PMID- 7733037
TI  - Plasma and platelet taurine are reduced in subjects with insulin-dependent
      diabetes mellitus: effects of taurine supplementation.
AB  - Plasma and platelet taurine concentrations were assayed in 39 patients with
      insulin-dependent diabetes mellitus (IDDM) and in 34 control subjects matched for
      age, sex, and both total and protein-derived daily energy intake. Platelet
      aggregation induced by arachidonic acid in vitro at baseline and after oral
      taurine supplementation (1.5 g/d) for 90 d was also studied. Plasma and platelet
      taurine concentrations (mean +/- SEM) were lower in diabetic patients (65.6 +/-
      3.1 mumol/L, or 0.66 +/- 0.07 mol/g protein) than in control subjects (93.3 +/-
      6.3 mumol/L, or 0.99 +/- 0.16 mol/g protein, P < 0.01). After oral
      supplementation, both plasma and platelet taurine concentrations increased
      significantly in the diabetic patients, reaching the mean values of healthy
      control subjects. The effective dose (mean +/- SEM) of arachidonic acid required
      for platelets to aggregate was significantly lower in diabetic patients than in
      control subjects (0.44 +/- 0.07 mmol compared with 0.77 +/- 0.02 mmol, P < 0.001,
      whereas after taurine supplementation it equaled the mean value for healthy
      control subjects (0.72 +/- 0.04 mmol). In in vitro experiments, taurine reduced
      platelet aggregation in diabetic patients in a dose-dependent manner, whereas 10
      mmol taurine/L did not modify aggregation in healthy subjects.

PMID- 7733038
TI  - Effects of diets containing high or low amounts of stearic acid on plasma
      lipoprotein fractions and fecal fatty acid excretion of men.
AB  - Ten middle-aged males participated in a crossover study to determine the
      cholesterolemic effect of high amounts of stearic acid in a natural diet. They
      consumed a 20-d stabilization diet followed by two 40-d intervention diets
      containing either 1.5% of energy as stearic (18:0) acid and 7.3% of energy as
      palmitic (16:0) acid (low stearate: LS) or 2.4% of energy as 16:0 and 7.3% of
      energy as 18:0 (high stearate: HS). The experimental diets also contained
      approximately 10% of energy each as saturated and monounsaturated fatty acids and
      7.2-8% of energy as polyunsaturated fatty acids. The primary source of 18:0 in
      the HS diet was sheanut oil (commercially referred to as shea butter) and palm
      oil and butter in the LS diet. Plasma total, low-density-lipoprotein, and high
      density-lipoprotein cholesterol were significantly lower with the HS than with
      the LS diet. Total fecal fatty acid excretion was higher throughout the HS
      period. Apparent digestibility of the major dietary fatty acids showed that all
      of the selected fatty acids, except 18:0, were > or = 95% absorbed. These data
      demonstrate that feeding diets containing about two times the usual amount of
      stearic acid consumed in the United States, contributed to an increase in plasma
      lipoprotein concentrations at 40 d from an earlier decrease at 20 d. The time
      required to achieve stable cholesterol concentrations appears to vary depending
      on the kind of saturated fatty acids present in the diet.

PMID- 7733039
TI  - Plasma cholesterol-predictive equations demonstrate that stearic acid is neutral
      and monounsaturated fatty acids are hypocholesterolemic.
AB  - In the present study we used regression analyses to evaluate the effects of
      stearic acid (18:0) on total cholesterol (TC), low-density-lipoprotein
      cholesterol (LDL-C), and high-density-lipoprotein-cholesterol (HDL-C)
      concentrations (mmol/L). Using data from 18 articles, we developed the following
      predictive equations (monounsaturated fatty acids, MUFAs; polyunsaturated fatty
      acids, PUFAs): delta TC = 0.0522 delta 12:0-16:0 - 0.0008 delta 18:0 - 0.0124
      delta MUFA - 0.0248 delta PUFA; delta LDL-C = 0.0378 delta 12:0-16:0 + 0.0018
      delta 18:0 - 0.0178 delta MUFA - 0.0248 delta PUFA; delta HDL-C = 0.0160 delta
      12:0-16:0 - 0.0016 delta 18:0 + 0.0101 delta MUFA + 0.0062 delta PUFA. Our
      analyses revealed that unlike the other long-chain saturated fatty acids (SFAs),
      stearic acid had no effect on TC and lipoprotein cholesterol concentrations in
      men and women. MUFAs elicited an independent hypocholesterolemic effect that we
      believe is due to the small amount of 12:0-16:0 in the experimental diets
      evaluated. The observation that stearic acid has unique effects on TC, LDL-C, and
      HDL-C provides additional compelling evidence that it be distinguished from the
      other major SFAs in blood cholesterol predictive equations.

PMID- 7733040
TI  - Rates of bone loss in postmenopausal women randomly assigned to one of two
      dosages of vitamin D.
AB  - We conducted a study to determine whether increasing vitamin D intake above the
      recommended dietary allowance (RDA) of 5.0 micrograms (200 IU)/d reduces bone
      loss in healthy postmenopausal women residing at latitude 42 degrees N. In this
      double-blind, randomized 2-y trial, we enrolled 247 healthy ambulatory
      postmenopausal women who consumed an average of 2.5 micrograms (100 IU) vitamin
      D/d in their usual diets. The women were given either 2.5 micrograms (100 IU) or
      17.5 micrograms (700 IU) vitamin D/d. All women received 500 mg supplemental
      calcium per day as citrate malate. Duplicate hip and spine and single whole-body
      scans were performed by dual-energy x-ray absorptiometry at 6-mo intervals
      selected to flank the periods when 25-hydroxycholecalciferol (calcidiol)
      concentrations are highest (summer/fall) and lowest (winter/spring). Plasma
      calcidiol and serum osteocalcin were measured in these seasons in year 1. Both
      treatment groups lost bone mineral density from the femoral neck, but the 17.5
      micrograms group lost less than (-1.06 +/- 0.34%; mean +/- SE) the 2.5-micrograms
      group (-2.54 +/- 0.37%, P = 0.003). Seventy percent of the benefit each year
      occurred in winter/spring and 30% in summer/fall. Changes in spinal and whole
      body bone densities did not differ by treatment group and were minimal after 2 y.
      Serum osteocalcin and plasma calcidiol (2.5-micrograms group only) fluctuated
      with season. In conclusion, in healthy, calcium-supplemented, postmenopausal
      women residing at latitude 42 degrees N, an intake of 5.0 micrograms (200 IU)
      vitamin D/d is sufficient to limit bone loss from the spine and whole body but it
      is not adequate to minimize bone loss from the femoral neck.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7733041
TI  - Comparison of the heart rate-monitoring and factorial methods: assessment of
      energy expenditure in highland and coastal Ecuadoreans.
AB  - Accurate estimates of total daily energy expenditure (TDEE) are critical to
      studies of the nutritional adaptation of human populations. This study compared
      the standard factorial method with the recently developed flex-HR technique in a
      sample of 32 adults (16 males, 16 females) from rural, agricultural communities
      of highland and coastal Ecuador. Although energy expenditures obtained from the
      two methods were highly correlated (r = 0.759, P < 0.0001), the 1985 FAO/WHO/UNU
      factorial method significantly underestimated TDEE relative to the heart rate
      monitoring technique (10.27 +/- 2.54 compared with 11.91 +/- 3.96 MJ/d, P <
      0.001). The degree of underestimation was greater in males, who had higher energy
      expenditures. Similarly, underestimation was greater in the highland farmers, who
      were studied during a period of heavy agricultural work. The differences in
      energy expenditure estimates translated into a 10% difference in estimated energy
      adequacy. Additional research is needed to identify the potential sources of bias
      in the factorial method and to further develop other techniques for accurately
      estimating energy expenditure under field conditions.

PMID- 7733042
TI  - Fortification of sugar with iron sodium ethylenediaminotetraacetate (FeNaEDTA)
      improves iron status in semirural Guatemalan populations.
AB  - A 32-mo-long, double-blind field study involving one highland control community
      receiving only vitamin A-fortified sugar and three vitamin A- and FeNaEDTA-sugar
      fortified communities, two in the lowlands and one in the highlands of Guatemala,
      was undertaken to test the effectiveness of this approach in controlling iron
      deficiency. The communities' population ranged between 1200 and 17000. Sugar
      fortified with 1 g FeNaEDTA and 15 mg retinol as retinyl palmitate/kg was stable,
      did not segregate, and was well accepted by the communities. The impact of
      fortification on iron nutrition was estimated at 8, 20, and 32 mo of
      intervention. All pregnant women and subjects with severe anemia received
      supplements or treatment and were excluded from the analysis. Iron stores in the
      fortified communities increased significantly except for women 18-48 y of age in
      one lowland community and > 49 y in the highland community. Iron stores in the
      control community remained unchanged except for a rise among adult males.

PMID- 7733043
TI  - The challenge of controlling iron deficiency: sweet news from Guatemala.

PMID- 7733044
TI  - Multiple- and single-frequency bioelectrical impedance analysis.

PMID- 7733045
TI  - Impedance measurements of body-water compartments.

PMID- 7733046
TI  - Ratio of bioavailability of RRR-/all-rac-alpha-tocopherol.

PMID- 7733047
TI  - Accuracy of DXA for body-composition measurements.

PMID- 7733049
TI  - The orthodontic community.

PMID- 7733048
TI  - Selenium status in aging.

PMID- 7733050
TI  - A changing America.

PMID- 7733051
TI  - Managed care--the Southern California perspective.

PMID- 7733052
TI  - Comment on health care reform.

PMID- 7733053
TI  - Further comments on the Kesling-Isaacson debate.

PMID- 7733054
TI  - In vitro enamel remineralization at orthodontic band margins cemented with glass
      ionomer cement.
AB  - Demineralization adjacent to orthodontic bands remains a clinical concern. The
      release of fluoride from glass ionomer cement has been shown to inhibit
      demineralization. The purpose of this study was to examine the remineralization
      effects of a glass ionomer cement adjacent to orthodontic bands. Forty extracted
      molars were painted with an acid-protective varnish, excluding a 2 x 6 mm window
      on the buccal surfaces. Artificial caries-like lesions were created in the
      exposed enamel with an acidified gel. Half the lesion on each tooth was then
      painted with an acid-protective varnish. An orthodontic band was cemented with a
      glass ionomer cement or zinc phosphate cement, the gingival margin of the band
      located at the level of the artificial carious lesion. The teeth were placed in
      separate closed environments of a nonfluoridated artificial saliva for 3 months.
      The teeth were then sectioned and photographed with polarized light microscopy in
      imbibition medias of water and Thoulet's (R.I.: 1.41, 1.47), representing a
      minimum of 5%, 10%, and 25% pore volume, respectively. With a sonic digitizer,
      the area of the body of the lesion was measured in each imbibition media,
      comparing the maintained varnished out lesions to the lesions exposed to the
      cement. Results demonstrated a statistically significant reduction in the body of
      the lesions (p < 0.005) for those exposed to the glass ionomer cement.

PMID- 7733055
TI  - Prediction of dental arch development: an assessment of Pont's Index in three
      human populations.
AB  - Pont's Index was established by Pont in 1909 to predict maxillary dental arch
      width from the sum of the mesiodistal diameters of the four maxillary incisors.
      The usefulness of Pont's Index is controversial and, as there has been a recent
      resurgence of interest in its clinical use for establishing dental arch
      development objectives particularly by nonspecialists, reassessment of the Index
      in different human populations was considered worthwhile. This study aimed to
      evaluate Pont's Index in untreated, noncrowded samples of Australian Aborigines
      (n = 80), Indonesians (N = 60), and white subjects (N = 60). Measurements were
      obtained directly from plaster casts; they included mesiodistal crown diameters
      of the four maxillary incisors, as well as intercanine, interpremolar and
      intermolar maxillary arch widths as specified by Pont. A series of double
      determinations confirmed the reliability of the method. Considerable individual
      variability was noted in each population with regard to the difference between
      observed values and Pont's estimates, ranging from -5.9 mm to +6.2 mm
      (interpremolar width) and -6.1 mm to +12.7 mm (intermolar width). No person
      displayed the ideal arch dimensions predicted by the Index, but values were
      within +/- 1.0 mm for 17.5% of the Indonesian sample, 20.6% of the Aboriginal
      sample, and 30.8% of the white sample. Dental arch width was generally
      underestimated by the Index in Indonesians who tended to display relatively small
      tooth size and large arch width. A more even distribution of estimates was noted
      in Australian Aborigines and white subjects, with the Aborigines showing large
      tooth size and broad dental arches, and the white subjects displaying smaller
      tooth size and narrow arches. Correlation coefficients computed between observed
      and expected values were low in all three populations studied (range r = 0.01 to
      r = 0.56). Although the concept of a simple index with predictive ability is very
      appealing to some clinicians, the results of this study have highlighted the
      marked variation in values of Pont's Index for persons with apparently good
      occlusions, representing three different human populations. Tooth size variation
      was poorly correlated with arch width variation, with persons often being over or
      under Pont's estimation due to variation in tooth dimension, particularly in the
      size of the maxillary lateral incisor. It is concluded that Pont's Index is
      unlikely to be a useful clinical predictor of dental arch width and the index
      should not be used as a guide to dental arch development in contemporary
      populations.

PMID- 7733056
TI  - Adolescent growth changes in soft tissue profile.
AB  - Growth of the lips, nose and chin was studied in a mixed longitudinal sample of
      82 subjects from the "Nijmegen Growth Study". The age range was between 9 and 14
      years with a single measurement at the age of 22 years. Differences in growth
      pattern between boys and girls are illustrated by mean cumulative growth curves
      and mean growth velocity curves as well as by contour plots.

PMID- 7733057
TI  - Clinical comparison between a glass ionomer cement and a composite for direct
      bonding of orthodontic brackets.
AB  - The clinical performance of a glass ionomer cement for direct bonding of
      orthodontic brackets was compared with a composite resin routinely used in this
      procedure. Brackets were bonded, using both materials, in alternate quadrants of
      16 patients of the Orthodontic Clinic of the State University of Rio de Janeiro.
      A total of 225 teeth, 112 in the glass ionomer cement group and 113 in the
      composite group, were tested. Bond failure frequencies were recorded for 12
      months, and chi-square statistical test was carried out comparing the failure
      rates of the materials. The composite showed a statistically significant lower
      failure rate (7.96%) than the glass ionomer cement (50.89%), regardless of the
      dental arch tested. Although the glass ionomer cement presents important
      properties not observed in the composite, it is necessary to increase its
      cohesive strength to permit its clinical use for direct bonding of orthodontic
      brackets.

PMID- 7733058
TI  - Extent and flux density of static magnetic fields generated by orthodontic
      samarium-cobalt magnets.
AB  - The aim of this study was to measure and to analyze the extent and flux density
      of static magnetic fields generated by commercially available samarium-cobalt
      magnets used in orthodontics. The flux density was measured with a gaussmeter and
      a Hall probe with the magnets mounted in clinically relevant positions, i.e., in
      attractive and in repelling positions and also in the single position.
      Furthermore, the flux density between new and clinically used and recycled
      magnets was compared. It was found that the maximum flux density was generated at
      the pole faces and that magnets in attractive positions produced the highest flux
      density (2.2 kG), followed by the single magnet (2.0 kG) and the repelling
      magnets (1.7 kG). The flux density decreased rapidly (exponentially) with
      increased distance from the magnets. The flux density was approximately the same
      or less than the flux density of the earth magnetism (0.3 to 0.7 G) 60 mm from
      the attractive magnets, 50 mm from the single magnets, and 35 mm from the
      repelling magnets. The difference in flux density between new and clinically used
      and recycled samarium-cobalt magnets was negligible. Thus, the static magnetic
      field exposure of surrounding tissues can be assumed to be low, and the
      conceivable risk of harmful biologic effects must be regarded as small and
      limited when the tested orthodontic magnets are used clinically.

PMID- 7733059
TI  - Effect of polyol gums on dental plaque in orthodontic patients.
AB  - Sixty 11- to 15-year-old children wearing fixed orthodontic appliances were given
      chewing gums containing polyol for daily use after meals and snacks, to study
      whether the chewing of gums that contained slowly fermentable polyols (xylitol
      and sorbitol) affects the amount of dental plaque and the number of mutans
      streptococci present in plaque and saliva. The 60 subjects were randomly divided
      into four groups, each of which was provided with a supply of 1.35 gm pellet
      shaped gums for a period of 1 month, as follows: (1) xylitol; (2) sorbitol; (3)
      xylitol-sorbitol mixture I (3:2); and (4) xylitol-sorbitol mixture II (4:1). In
      each group, two pellets with a total initial gum mass of 2.7 gm (maximum polyol
      dose per day: 10.5 gm), were used six times a day. The fresh and dry weight of
      dental plaque, collected at baseline and 28 days later from incisors, canines,
      and premolars from the area between gingival margin and the bracket, reduced in
      all groups, but most significantly (by 43% to 47%) in children receiving xylitol
      gum. The plaque and saliva levels of mutans streptococci did not change in the
      sorbitol group, but was significantly (in most cases) reduced by 13% to 33% in
      groups that received gum containing xylitol. Provided that the quantity of dental
      plaque and the plaque and salivary levels of mutans streptococci can be regarded
      as risk factors in dental caries, these results suggest that regular use of
      polyol gum--and especially gum that contains xylitol as the predominant sweetener
      -can reduce the caries risk in young patients wearing fixed orthodontic
      appliances.

PMID- 7733060
TI  - Classification of maxillary tooth transpositions.
AB  - Tooth transposition is a severe disturbance of tooth order and eruptive position,
      involving certain teeth, that may occur at any of several specific sites in the
      mouth. Published cases of transposition involving maxillary teeth were gathered
      from worldwide sources to study, identify, and classify these occurrences of
      orthodontic interest. With a sample of 201 cases and on the basis of anatomic
      factors, five types of maxillary tooth transpositions were discerned: canine-
      first premolar (Mx.C.P1), 143 cases; canine--lateral incisor (Mx.C.I2), 40 cases;
      canine to first molar site (Mx.C to M1), 8 cases; lateral incisor--central
      incisor (Mx.I2.I1), 6 cases; and canine to central incisor site (Mx.C to I1), 4
      cases. As a benefit from this large-scaled study of an uncommon anomaly, new
      analyses are presented on cause and treatment aspects for each of these five
      classes of maxillary tooth transpositions.

PMID- 7733061
TI  - Long-term changes in arch form after orthodontic treatment and retention.
AB  - The purpose of this study was to evaluate the long-term stability of
      orthodontically induced changes in maxillary and mandibular arch form. Dental
      casts were evaluated before treatment, after treatment, and a minimum of 10 years
      after retention for 45 patients with Class I and 42 Class II, Division 1
      malocclusions who received four first premolar extraction treatment. Computer
      generated arch forms were used to assess changes in arch shape over time. Buccal
      cusp tips of first molars, premolars, and canines plus mesial, distal, and
      central incisal aspects of incisors were marked, photocopied, and digitized in a
      standardized manner. An algorithm was used to fit conic sections to the digitized
      points. The shape of the fitted conics at each time period was described by
      calculating the parameter eccentricity; a small value represented a more rounded
      shape and a larger value represented a more tapered shape. Findings demonstrated
      a rounding of arch form during treatment followed by a change to more tapered.
      Arch form tended to return toward the pretreatment shape after retention. The
      greater the treatment change, the greater the tendency for postretention change.
      However, individual variation was considerable. The patient's pretreatment arch
      form appeared to be the best guide to future arch form stability, but minimizing
      treatment change was no guarantee of postretention stability.

PMID- 7733062
TI  - Surgically assisted rapid orthodontic lengthening of the maxilla in primates--a
      pilot study.
AB  - Orthodontic and surgical treatment of patients with maxillary retrusion and/or
      midface hypoplasia is challenging. This study was designed to show that the
      maxilla can be successfully lengthened by surgical assisted rapid orthopedic
      movement, using the principles of distraction osteogenesis. Three experimental
      and three control adolescent cynomolgus primates were used in this study.
      Metallic markers were placed in the cranial base and the maxilla and
      cephalometric x-ray films were taken. An orthodontic appliance was constructed
      with a Glen-Ross screw (Dentaurum, Newtown, Pa.) oriented anteroposteriorly.
      Anterior supraapical osteotomies of the maxilla were carried out. Bilateral
      horizontal and interdental osteotomies were created between the first premolars
      and the canine; the anterior six tooth dental-osseo segment was completely
      mobilized in all animals. Beginning 1 week after surgery, the orthodontic
      appliance was opened a quarter turn every 2 days until the anterior segment was
      advanced by 4 mm in two animals and 6 mm in one animal. Animals were killed at 6,
      8, and 12 weeks after completion of the maxillary orthopedic advancement.
      Computerized tomographic scans of the maxillae were completed, and the specimens
      were then prepared by routine histologic methods for examination by light
      microscopy. The computerized tomographic scans showed bone deposition in the
      osteotomy sites, which was confirmed by histologic observations. Since this
      technique demonstrated repair by bone rather than soft connective tissue in the
      osteotomy sites, this procedure could be a useful method of treating midface
      retrusion.

PMID- 7733063
TI  - The Frankfort horizontal as a basis for cephalometric analysis.
AB  - A random sample of 79 British 12-year-old children was studied from tracings
      registered in the natural head position (NHP). The angle between the Frankfort
      horizontal (FH) and the horizontal at right angles to the plumb line was
      measured. Two experienced assessors checked every tracing; for those children
      perceived to show unnatural head position this was adjusted to what they
      considered to be the natural head orientation (NHO). The NHO was defined as the
      head orientation of the subject perceived by the clinician, based on general
      experience, as the NHP in a standing, relaxed body and head posture, when the
      subject is looking at a distant point at eye level. The FHK horizontal angle was
      then measured, now related to the corrected head position. The standard deviation
      for the latter angle was smaller than that of the uncorrected, but still too
      large for the FH to be considered reliable as a basis for clinical cephalometric
      analysis. No statistically significant difference in variability as found between
      FH and the sella-nasion line. The extracranial horizontal plane related to NHO
      was recommended as the least variable of the references studied.

PMID- 7733064
TI  - Orthodontic diagnosis and treatment analysis--concepts and values: Part II.
AB  - Orthodontic treatment must be harmonious with normal growth and developmental
      patterns. Also, force systems used during malocclusion correction should attempt
      to improve or compensate the less normal patterns. Because orthodontic treatment
      is generally undertaken during the time when the patient is experiencing growth
      and development, to treat harmoniously with growth is a serious responsibility
      for the clinical orthodontist. By using control, successfully treated, and
      unsuccessfully treated samples, this article identifies some areas that must be
      controlled if orthodontic mechanotherapy is to be successful. Some suggestions
      for diagnosis and treatment management are made after a careful analysis of the
      three samples.

PMID- 7733065
TI  - The importance of occlusal plane control during orthodontic mechanotherapy.
AB  - Control of the occlusal plane during orthodontic mechanotherapy should be an
      integral part of every clinician's treatment plan. The many ramifications of
      occlusal plane control during the treatment of normodivergent, hyperdivergent,
      and hypodivergent skeletal patterns are discussed. The force systems and
      treatment mechanics used during treatment of the three different skeletal types
      and the impact these systems have on occlusal plane control are explained.

PMID- 7733066
TI  - Coenraad Frans August Moorrees.

PMID- 7733067
TI  - Upgrading a hard drive.

PMID- 7733068
TI  - Hither and yon: the locality rule.

PMID- 7733069
TI  - Esophageal peristalsis and achalasia.

PMID- 7733070
TI  - Toward an optimal treatment of Helicobacter pylori-positive peptic ulcers.

PMID- 7733071
TI  - Bockus Lecture: World Congress of Gastroenterology, Los Angeles, CA--October 3,
      1994. The management of acute pancreatitis: a critical assessment as Dr. Bockus
      would have wished.

PMID- 7733072
TI  - Evaluating risk: a primer for gastroenterologists.
AB  - OBJECTIVE: To review the various types of risk measures and to illustrate how
      interpretations may vary depending on how risk is presented. METHODS: We define
      different types of risk estimates and provide examples of their use from the
      recent gastroenterological literature. RESULTS: Calculations of absolute risk and
      the number of patients who must receive treatment to prevent one patient from
      experiencing a disease state (number needed to treat) provide useful information
      in assessing the utility of fecal occult blood testing for prevention of
      colorectal cancer and in estimating small bowel cancer rates for individuals with
      familial adenomatous polyposis. CONCLUSIONS: Measures such as relative risk and
      the odds ratio are best used in analyzing causality but may not be helpful in
      guiding clinical decisions. Absolute risk and attributable risk reveal the actual
      number of cases that can be explained by a given exposure and can thereby measure
      the impact of a clinical intervention for both the population and the patient.
      These measures should be the criteria for decision-making.

PMID- 7733073
TI  - Stress ulcer: is routine prophylaxis necessary?
AB  - Recent observations have suggested that stress ulcer prophylaxis should not
      routinely be used to prevent upper gastrointestinal hemorrhage in critically ill
      patients. This is because our understanding of stress ulcer pathogenesis has
      shifted from a problem limited to back diffusion of acid to a phenomenon of
      gastric ischemia. The purpose of this article is to review the proposed mechanism
      of stress ulcer bleeding and to discuss prophylaxis.

PMID- 7733074
TI  - Factors involved in the return of peristalsis in patients with achalasia of the
      cardia after Heller's myotomy.
AB  - OBJECTIVE: To assess the reappearance of peristalsis in a group of 45 patients
      with achalasia of the cardia undergoing surgery and to analyze the factors
      involved in this phenomenon. METHODS: According to the postoperative manometric
      data, the 45 patients were divided into two groups, depending on whether or not
      they presented a return of peristalsis. A statistical comparison of age, sex,
      duration of the disease, pre- and postoperative radiological diameter of the
      esophagus, classic or vigorous nature of the achalasia, and manometric data of
      the lower esophageal sphincter and esophageal body was made. RESULTS: In 46.6% of
      the patients, peristalsis returned to the upper esophagus, and 100% of the waves
      were progressive; in 24.4%, peristalsis returned to the middle third also, but
      only 50% of the waves were progressive; and in 8.8% (four patients), peristalic
      activity returned to the whole esophagus, but only 40% of the waves were
      progressive. The group of patients with a return of peristalsis had a shorter
      duration of dysphagia, less preoperative dilation of the esophagus, and a greater
      contractile activity of the esophageal body. CONCLUSIONS: Return of peristalsis
      is a frequent phenomenon after myotomy in patients with achalasia of the cardia,
      especially in cases of short clinical evolution, little esophageal dilation, and
      a conserved contractile capacity, although its accurate production mechanism is
      unknown.

PMID- 7733075
TI  - Impact of colloidal bismuth subnitrate in the eradication rates of Helicobacter
      pylori infection-associated duodenal ulcer using a short treatment regimen with
      omeprazole and clarithromycin: a randomized study.
AB  - Recent trials have shown that duodenal ulcers treated by H2-blockers heal faster
      if Helicobacter pylori is eradicated concurrently. OBJECTIVES: To evaluate the
      efficacy of a short treatment regimen in H. pylori eradication and ulcer healing
      and to assess the impact of colloidal bismuth subnitrate (CBS) in H. pylori
      eradication rate. METHODS: Sixty-one patients with H. pylori-associated duodenal
      ulcer were randomized in two short treatment groups. Group A patients (31) were
      given omeprazole 20 mg b.i.d. x 8 days. Clarithromycin (500 mg, b.i.d.) and CBS
      (120 mg, q.i.d.) were added 24 h after starting omeprazole and were given for 7
      days. Group B patients (30) were treated as group A patients but without CBS.
      Endoscopies were performed at entry and 4 wk after the end of treatment. Presence
      of H. pylori was assessed at each endoscopy by urease test, and biopsy specimens
      were examined for histological evidence of gastritis and by Gram stain and
      culture for H. pylori infection. No patient received follow-up treatment.
      RESULTS: H. pylori eradication rates were achieved in 25/31 (80.6%) group A
      patients and in 15/30 (50%) in group B patients (p = 0.012). Duodenal ulcer
      healing was documented in 30/31 (96.8%) patients in group A and in 25/30 (83%)
      patients in group B. CONCLUSIONS: The addition of CBS to the double therapy with
      omeprazole and clarithromycin substantially improves the eradication rate of H.
      pylori. Short therapy with omeprazole 20 mg/b.i.d., clarithromycin 500 mg/b.i.d.,
      and CBS 120 mg/q.i.d. is a safe, well tolerated combination that achieves a 80.6%
      eradication rate of H. pylori and duodenal ulcer healing rates as good as those
      achieved by omeprazole 20 mg/d when given for 4 wk.

PMID- 7733076
TI  - Benign, dysplastic, or malignant--making sense of endoscopic bile duct brush
      cytology: results in 149 consecutive patients.
AB  - OBJECTIVES: To determine the efficacy of endoscopic bile duct brush cytology for
      diagnosis of pancreaticobiliary malignancies and to provide guidelines for
      interpretation of dysplastic cytology. METHODS: Consecutive endoscopic bile duct
      brush cytology specimens were classified by an independent cytopathologist as
      benign, low- or high-grade dysplasia, or cancer. A final diagnosis was
      established in a blinded fashion by histopathology, radiographic evidence of
      metastatic disease, or independent clinical follow-up. Sensitivity and
      specificity were adjusted for dysplastic cytology, and likelihood ratios were
      determined for each diagnosis and used for calculation of posttest probability of
      malignancy. RESULTS: Dysplasia was found in 23% of 168 consecutive bile duct
      brushings performed in 149 patients. Sensitivity of brush cytology was 37% and
      specificity 100%; its likelihood ratio for malignancy ranged from 3.4 for high
      grade dysplasia, to 1.1 for low-grade dysplasia, to 0.6 for benign. For a patient
      with a 50% pretest probability of malignancy, finding of high-grade dysplasia
      changed the posttest probability to 77%, low-grade dysplasia to 52%, and benign
      to 38%. CONCLUSION: Cytological dysplasia occurs frequently, with high-grade
      dysplasia being strongly suggestive of malignancy. Presented likelihood ratios
      can be used to calculate the posttest probability of malignancy for any
      diagnosis.

PMID- 7733077
TI  - Endoscopic sphincterotomy for suspected choledocholithiasis in patients with and
      without stones.
AB  - OBJECTIVE: To characterize a subgroup of patients treated with endoscopic
      sphincterotomy (ES) for a suspected common bile duct lithiasis (CBDL) that was
      not confirmed and to compare it with the subgroup with confirmed CBDL. METHODS
      AND RESULTS: Over 18 months, ES was successful in 245 consecutive patients (age
      23-97, mean 75 yr, SE 17 yr) with suspected CBDL; 159 patients had CBDL (group
      1), and 86 did not (group 2), as confirmed by CBD exploration. Fifty-nine percent
      of the patients in group 1 and 76.7% of the patients in group 2 had gallbladder
      in situ. Both groups were different for age (p < 0.001), prevalence of chronic
      alcoholism (p < 0.001), gallbladder in situ (p < 0.01), and gallbladder stones (p
      < 0.05). Patients from group 1 had two or more presenting symptoms suggestive of
      CBDL more often than patients from group 2 (p < 0.05), and pancreatitis was a
      more frequent presenting manifestation in group 2 (p < 0.0001). Overall morbidity
      and mortality were not different between groups, but acute cholecystitis
      developed in six patients from group 2 and in one patient from group 1 (p <
      0.01). In a univariate analysis, only elevated alkaline phosphatase and a dilated
      common bile duct were positively discriminant for the diagnosis of CBDL; chronic
      alcoholism was negatively discriminant for the diagnosis of CBDL. In a
      multivariate analysis, only chronic alcoholism and a dilated bile duct were found
      to be independently discriminant. CONCLUSION: The risk of ES-related
      complications in the group without CBDL suggests that the selection of patients
      should be improved by a better use of preoperative criteria.

PMID- 7733078
TI  - Prolonged medical therapy for severe pediatric ulcerative colitis.
AB  - OBJECTIVES: The optimal timing of surgical intervention for severe ulcerative
      colitis remains uncertain. Numerous reports recommend surgery within 10-14 days
      if clinical remission is not achieved. We undertook a study to follow the
      clinical course and long-term follow-up of patients with severe ulcerative
      colitis treated medically for longer than 14 days (n = 11). METHODS: We performed
      a retrospective review of all patients admitted to the hospital with a diagnosis
      of severe ulcerative colitis who were treated for more than 14 days. RESULTS:
      Nine percent of patients (n = 1) required surgery during their hospitalization.
      Ninety-one percent of patients (n = 10, mean age 8.6 yr, 7 M, 3 F) treated with
      medical and nutritional therapy for more than 14 days went into clinical
      remission. Of these, only 10% (n = 1) ultimately required surgery; 60% remain in
      clinical remission up to 83 months posthospitalization (mean follow-up, 49.5
      months), whereas 30% suffer from mild to moderate colitis (mean follow-up, 26.3
      months). CONCLUSIONS: These results do not support the recommendation for
      colectomy for refractory severe ulcerative colitis if remission is not noted
      within 2 wk of hospitalization.

PMID- 7733079
TI  - Low Pentasa dosage versus hydrocortisone in the topical treatment of active
      ulcerative colitis: a randomized, double-blind study.
AB  - OBJECTIVES: To compare a low dosage (1 g/day) rectal preparation of 5
      aminosalicylic acid in slightly acidic, buffered suspension (Pentasa) with a
      hydrocortisone 100 mg/day enema (Cortenema). METHODS: Fifty-two patients with
      mild to moderate distal ulcerative colitis were randomized under double-blind
      conditions to receive a rectal preparation of either Pentasa (1 g/day) or
      Cortenema (100 mg/day) for 3 wk. RESULTS: After 3 wk, both types of treatment
      resulted in statistically significant improvements in clinical and endoscopic
      activity. No significant difference was observed between the two drugs in any of
      the parameters considered, although a statistical trend in favor of Pentasa was
      evident when analysis was limited to clinical activity (p = 0.07). No side
      effects were reported in either group. CONCLUSIONS: Our experience confirms that
      short term topical treatment with a low dosage 5-aminosalicylic acid is at least
      as effective as 100-mg hydrocortisone enemas in treating mild to moderate distal
      ulcerative colitis and is generally well tolerated.

PMID- 7733080
TI  - Antineutrophil cytoplasmic antibody correlates with chronic pouchitis after ileal
      pouch-anal anastomosis.
AB  - BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies, present in 60% of
      patients with ulcerative colitis, may be a marker for a genetically distinct
      subset of patients who develop chronic pouchitis after undergoing ileal pouch
      anal anastomosis. The frequency of these antibodies in chronic pouchitis was
      determined. METHODS: Four groups were studied: patients who underwent ileal pouch
      anal anastomosis for colitis with and without chronic pouchitis, familial
      polyposis without pouchitis and ileostomy for colitis. Antineutrophil cytoplasmic
      antibody levels and titers were detected by ELISA, and positive results were
      confirmed by perinuclear staining with indirect immunofluorescence. RESULTS: The
      frequency of perinuclear antineutrophil cytoplasmic antibodies in chronic
      pouchitis (100%) was significantly greater than in colitis (50%) or familial
      polyposis (0%) without pouchitis and colitis with an ileostomy (70%); p = 0.00,
      0.00, and 0.01, respectively. CONCLUSIONS: The finding that perinuclear
      antineutrophil cytoplasmic antibodies occur more frequently in patients with
      chronic pouchitis raises the possibility that this antibody may mark a
      genetically distinct subset of ulcerative colitis patients. Further studies are
      needed to determine whether the presence of this antibody before ileal pouch-anal
      anastomosis is predictive for later development of chronic pouchitis.

PMID- 7733081
TI  - Physiological tests to predict long-term outcome of total abdominal colectomy for
      intractable constipation.
AB  - OBJECTIVE: Total abdominal colectomy (TAC) for intractable constipation has a
      variable reported success rate that decreases to 50% beyond 2 yr. We hypothesize
      that this inconsistent outcome can be explained by a more extensive intestinal
      involvement in some patients. DESIGN: A consecutive sample of patients with
      intractable constipation had preoperative evaluations that included both upper
      and lower GI studies. Stool frequency, constipation, diarrhea, abdominal pain,
      and laxative or enema requirements were compared before and after operation. The
      study took place in an academic referral center and included 37 consecutive
      referred patients with severe intractable constipation and colonic dysmotility
      documented by radiopaque marker studies. INTERVENTIONS: TAC, with ileoproctostomy
      in 34 patients and ileostomy in three. MAIN OUTCOME MEASURES: Patients with
      motility abnormalities only of the lower GI tract were diagnosed as having
      colonic inertia (CI). Those with motility disorders of both the upper and the
      lower GI tracts were considered to have generalized intestinal dysmotility (GID)
      with colon predominance. RESULTS: Twenty-one patients had CI, and 16 had GID.
      Ninety percent of CI patients undergoing TAC had a successful outcome with a mean
      of 23 bowel movements (BMs)/wk at a mean follow-up of 7.5 yr. Although 88% of GID
      patients had initial improvement, with a mean of 19 BMs/wk at 6 months, only 13%
      had prolonged relief. After 2 yr, nine of the GID patients had recurrent
      constipation, and three had severe diarrhea. CONCLUSIONS: This study has
      identified two distinct types of colonic dysmotility, CI and GID. It has
      demonstrated the long-term success of TAC for CI and the importance of upper GI
      physiological studies to identify colon-predominant GID, which has a poor long
      term response to TAC.

PMID- 7733082
TI  - Effect of naproxen on gastroesophageal reflux and esophageal function: a
      randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVES: Gastrointestinal symptoms, particularly pyrosis, complicate
      nonsteroidal anti-inflammatory drug (NSAID) use. NSAIDs cause esophageal injury,
      and H2 blockers are often prescribed for, and successfully control, NSAID-related
      symptoms. To determine whether NSAIDs can induce gastroesophageal reflux, we
      studied the effect of a commonly used NSAID, naproxen, on reflux parameters and
      esophageal function. METHODS: Nine healthy volunteers (five males, four females,
      age 23-34 yr) were studied. After basal measurements were taken, the subjects
      randomly received naproxen 500 mg p.o. b.i.d. or placebo for 1 wk. On day 6, the
      subjects underwent esophageal manometry with a water-perfused system and Dent
      sleeve. Body pressures, contraction velocity, and duration of contraction were
      recorded in the distal 7 cm of the esophagus. The lower esophageal sphincter
      pressure (LESP) and number of transient relaxations (TLESRs) were monitored. This
      was followed by 24-h pH monitoring. The subjects then crossed over to the other
      drug after a minimum 14-day wash-out period. RESULTS: No subject experienced any
      GI symptoms during the study. One subject developed reflux-induced symptoms a few
      months after completing the study and was excluded from the analysis. The total
      fraction of time (pH < 4) was 4.9 +/- 1.0% in the basal state, 5.5 +/- 1.4% on
      placebo, and 5.4 +/- 1.5% on naproxen. These differences were not significant.
      The number of reflux episodes and the esophageal clearance time were not affected
      by naproxen. The LESP in the basal state was 32.1 +/- 5.6 mm Hg, 32.3 +/- 4.2 mm
      Hg on placebo, and 29.9 +/- 3.3 mm Hg on naproxen (p = NS). The number of TLESRs
      per 30 minutes in the basal state was 3.5 +/- 0.9, 4.6 +/- 1.2 on placebo, and
      5.8 +/- 1.0 on naproxen (p = NS). The speed and duration of contractions were not
      affected by naproxen. The excluded subject had marked basal reflux (total
      fraction of time pH < 4 = 10.7%), low LESP (8 mm Hg), and a marked increase in
      reflux on naproxen (total fraction of time pH < 4 = 53%). CONCLUSIONS: Naproxen
      did not induce reflux in normal subjects, although reflux did increase in some
      subjects. Naproxen had no significant effect on motility parameters. Our data
      suggest that NSAIDs do not impair the anti-reflux barrier or induce reflux.
      Pyrosis experienced during NSAID use may not arise from the esophagus or may
      reflect altered esophageal sensitivity. A single subject with decreased LESP and
      asymptomatic increased acid exposure in the basal state had a marked increase in
      reflux on naproxen. This person subsequently developed symptomatic
      gastroesophageal reflux. The effect of NSAIDs on individuals with a propensity to
      reflux deserves further study.

PMID- 7733083
TI  - Distribution of adenomatous polyps in African-Americans.
AB  - OBJECTIVES: Previous research has suggested that polyps and colon cancer occur
      more commonly in the right colon in African-Americans compared with the general
      population. The purpose of this study is to determine the pattern of distribution
      of colonic polyps in African-Americans. METHODS: We retrospectively evaluated 141
      colonoscopies in which 179 polypectomies were done. The polyps were described on
      the basis of anatomical distribution, gross description, size, and histology.
      Sixty-nine males and 72 females had colonoscopic polypectomies. The mean age was
      67 yr (range, 43-91 yr). RESULTS: Seventy-seven (43%) were classified as left
      sided, and 102 (57%) were right sided. Left-sided polyps were more likely to be
      pedunculated than right-sided polyps (p < 0.01). Larger polyps were more common
      on the left side than the right side (p < 0.01), but villous histology was almost
      as high on the right side as on the left side. Polyps that had the highest
      malignant potential were found almost as commonly on the right side as on the
      left side. CONCLUSIONS: This study supports previous work that suggests that
      there is a significant shift to the right in the anatomical distribution of
      polyps in African-Americans. It also shows that the malignant potential is as
      high for right-sided polyps as it is for those on the left. Current screening
      recommendations may not be effective enough for preventing colon cancer in this
      population.

PMID- 7733084
TI  - Endoscopic findings and clinical manifestation of gastric anisakiasis.
AB  - OBJECTIVES: To identify the endoscopic findings and clinical manifestations of
      anisakiasis, we studied 87 cases of gastric anisakiasis. METHODS: Patient
      information was analyzed by means of patient records. The interval between the
      day of intake of Anisakis and endoscopic examination was determined in 86 cases.
      Then the endoscopic findings of each interval were elucidated. RESULTS: Moderate
      to severe gastric mucosal edema tends to occur within 1 or 2 days after Anisakis
      infection, accompanied by leukocytosis. As to the sites of penetration of
      Anisakis, 55% of cases were found in the greater curvature with severe mucosal
      edema. Among 87 cases, four patients experienced anisakiasis twice during the
      interval examined, and six patients had past histories of anisakiasis before the
      investigated interval. CONCLUSIONS: Gastric anisakiasis may be caused by an
      allergic reaction to the Anisakis antigen. There is a classic relationship
      between clinical and endoscopic findings and the interval after Anisakis
      administration. Anisakis usually is found in the greater curvature.

PMID- 7733085
TI  - Enterically transmitted non-A, non-B hepatitis mimicking acute cholecystitis.
AB  - OBJECTIVES: To study the significance of cholecystitis-like presentation and
      increased gallbladder wall thickness (GBWT) in patients with acute viral
      hepatitis (AVH). METHODS: Sixty-seven consecutive patients with acute viral
      hepatitis (hepatitis A:3, hepatitis B:13, and enterically transmitted non-A, non
      B hepatitis: 51) were included in this prospective study. Clinical assessment and
      sonographic evaluation of the GBWT were carried out every week until recovery
      from acute hepatitis. RESULTS: The clinical presentation in 16 patients with
      hepatitis A and B and in 29 patients with enterically transmitted non-A, non-B
      hepatitis (ET-NANB hepatitis) was typical of AVH, and the mean GBWT in these
      patients was 6.16 +/- 2.23 mm and 7.28 +/- 2.93 mm, respectively. The remaining
      22 patients with ET-NANB hepatitis presented with features suggestive of acute
      cholecystitis (fever, severe pain, and tenderness right hypochondrium), and the
      mean GBWT in these patients (10.18 +/- 2.58 mm) was significantly higher compared
      with the rest of the patients with AVH (p < 0.001). The mean GBWT in patients
      with AVH (7.31 +/- 0.97 mm) was significantly higher compared with controls (1.76
      +/- 2.17 mm) (p < 0.001). All patients with acute cholecystitis-like presentation
      recovered with conservative medical management. A time-dependent normalization of
      the thickened gallbladder wall was observed in all the patients within 6 wk.
      CONCLUSION: A proportion of our patients with ET-NANB hepatitis presented with
      acute cholecystitis-like picture and had markedly thickened gallbladder wall on
      ultrasonography. These patients made an uneventful recovery, and the sonographic
      abnormalities disappeared within 6 wk.

PMID- 7733086
TI  - Rupture of pyogenic liver abscess.
AB  - OBJECTIVE: Our objective was to study the clinical manifestations, course,
      treatment, and results obtained in 23 patients with ruptured pyogenic liver
      abscess and compare these findings with those of nonruptured cases. METHODS: Four
      hundred twenty-four patients with clinical diagnoses of pyogenic liver abscess
      were enrolled in the study. Among these, 23 patients had ruptured pyogenic liver
      abscess. The clinical manifestations, incidence of septic shock, laboratory
      findings, concurrent diabetes mellitus, etiology of abscess, and results of the
      treatment were recorded. Qualitative data were analyzed by chi 2 test, and
      quantitative data were analyzed by Student's t test. RESULTS: Except for
      abdominal pain and septic shock, other symptoms, such as fever, chills, and
      jaundice, were similar in ruptured and nonruptured groups. Laboratory findings
      indicated that the group with ruptured liver abscess had higher levels of
      bilirubin, blood glucose, and aspartate aminotransferase than the non-ruptured
      group. Of the patients with ruptured abscess, 14 (60.9%) had diabetes mellitus
      and 15 (65.2%) were cryptogenic. Klebsiella pneumoniae was the bacteria most
      often isolated in both blood cultures and liver aspirates. Surgical intervention-
      draining the abscess and cleaning the abdominal cavity--was the only means of
      saving the patients' lives. The overall mortality rate was higher in this group
      (43.5%) than in the nonruptured group (15.5%). CONCLUSIONS: Ruptured pyogenic
      liver abscess should be suspected if septic shock and diffuse abdominal pain are
      found in a patient with pyogenic liver abscess, concurrent with high levels of
      bilirubin, aspartate aminotransferase, and blood glucose. Surgery is the only
      treatment for this condition.

PMID- 7733087
TI  - Serum autoantibody against interleukin-1 alpha is unrelated to the etiology or
      activity of liver disease but can be raised by interferon treatment.
AB  - OBJECTIVE: To clarify the clinical significance of serum levels of interleukin-1
      alpha autoantibody in liver disease and their change during interferon therapy
      for chronic hepatitis. METHODS: By radioimmunoassay, we studied the incidence of
      serum interleukin-1 alpha autoantibody in 838 healthy controls and 180 patients
      with liver disease and monitored the change in antibody titer during the
      interferon therapy for chronic hepatitis. RESULTS: We detected the interleukin-1
      alpha autoantibody in 12.6% (106/838) of healthy controls. In patients with liver
      disease, we found the antibody in 15.6% (5/32) in patients with acute hepatitis,
      16.3% (13/80) in patients with chronic hepatitis, 18.8% (9/48) in patients with
      liver cirrhosis, and 15% (3/20) in patients with autoimmune liver disease. The
      incidence was not related to either etiology or inflammatory activity of liver
      disease. Two of three chronic hepatitis patients with initially high serum levels
      of the antibody (> 2000 ng/ml) showed transient increase in antibody titers
      during interferon therapy. CONCLUSION: The serum level of interleukin-1 alpha
      autoantibody was unrelated to the etiology or activity of liver disease.
      Interferon therapy can cause transient elevation of serum interleukin-1 alpha
      autoantibody levels.

PMID- 7733088
TI  - Increased serum type IV collagen 7-S levels in patients with hepatic metastasis.
AB  - OBJECTIVE: The purpose of this study was to assess serum type IV collagen 7-S
      domain (IV 7-S) levels in colorectal cancer patients with hepatic metastasis and
      to investigate the relation between serum IV 7-S levels and type IV collagenase
      activities in tumor tissue. METHODS: Tissue type IV collagenase activity and
      serum IV 7-S were measured in 50 colorectal cancer patients without hepatic
      metastasis and in 26 patients with hepatic metastasis. RESULTS: Type IV
      collagenase showed significantly higher activities in colorectal cancer (n = 36)
      than in colorectal normal mucosa (n = 36) (p < 0.001), but significantly lower
      activities were shown in the hepatic metastatic tumor (n = 18) than in the
      primary tumor (n = 36) and normal liver tissue (n = 18) (p < 0.001). No
      significant correlation was found between type IV collagenase activities in the
      tumor and serum IV 7-S levels. Colorectal cancer patients with hepatic metastasis
      (n = 26) had significantly higher serum IV 7-S levels than those without hepatic
      metastasis (n = 50) (p < 0.001). Moreover, serum IV 7-S levels correlated
      significantly with hepatic metastatic tumor volume in patients with synchronous
      (r = 0.719, p < 0.001, n = 26) and in patients with metachronous (r = 0.910, p <
      0.001, n = 16) hepatic metastasis. CONCLUSION: We suggest that serum IV 7-S
      levels may increase in hepatic metastasis, not by the degradation of type IV
      collagen in the primary and secondary tumors, but by the enhanced production of
      type IV collagen responsive to hepatic metastasis. The measurement of serum IV 7
      S levels might be a useful tumor marker of hepatic metastasis reflecting hepatic
      metastatic tumor volume.

PMID- 7733089
TI  - Oral administration of nipradilol and the acute and chronic splanchnic
      hemodynamic effects of a new beta-blocker with nitrovasodilating properties in
      patients with liver cirrhosis.
AB  - OBJECTIVES: We studied the effects of nipradilol, which has both a nonselective
      beta-blocker action and a vasodilating action similar to nitroglycerin, on portal
      hypertension. METHODS: We measured hepatic venous pressure gradient and
      splanchnic and systemic hemodynamics before beginning therapy, 2 h after an oral
      dose of 6 mg, and after either 6 months of nipradilol 6 mg twice a day (n = 14)
      or of a placebo (n = 6) in 20 cirrhotic patients. RESULTS: No significant changes
      were observed after the administration of the placebo. Oral nipradilol induced a
      significant reduction in the hepatic venous pressure gradient (base line: 14.8 +/
      3.2 mm Hg vs 2 h: 12.3 +/- 3.4 mm Hg, p < 0.01; 6 mo: 12.5 +/- 3.2 mm Hg, p <
      0.05) without a significant change in the free hepatic venous pressure. The
      hepatic vascular resistance decreased significantly (base line: 1811 +/- 778
      dyn.sec.cm-5 vs 2 h: 1540 +/- 701 dyn.sec.cm-5, p < 0.05; 6 mo: 1564 +/- 693
      dyn.sec.cm-5, p < 0.05) without a significant change in hepatic blood flow. A
      decrease in the hepatic venous pressure gradient greater than 10% was observed in
      nine patients (64%), defined as "responders," at 2 h and in 10 patients (71%) at
      6 months. The reduction of mean heart rate and hepatic venous pressure gradient
      in these responders was 16.2% and 28.3% at 2 h and 15.1% and 27.1% at 6 months,
      respectively. CONCLUSIONS: We found that in some cirrhotic patients, at the doses
      used in this study, long term oral nipradilol administration produces a reduction
      in the hepatic venous pressure gradient with both a beta-blocking and a
      nitrovasodilating action.

PMID- 7733090
TI  - Posttraumatic pancreatic fistula cured by endoprosthesis in the pancreatic duct.
AB  - We report a case of pancreatic fistula attributable to posttraumatic rupture of
      the main duct that was undiagnosed before ERCP and was cured instantaneously by
      endoscopic placement of an endoprosthesis in the pancreatic duct after failure of
      conventional medical treatment.

PMID- 7733091
TI  - Gastrointestinal bleeding due to delayed perianastomotic ulceration in children.
AB  - Delayed perianastomotic ulcers are a poorly recognized complication of intestinal
      surgery. We report two patients with this complication of their remote intestinal
      surgery who developed significant iron deficiency anemia. Patient 1 had
      intestinal resection for perforated necrotizing enterocolitis as a newborn and
      presented at 16 yr of age with an ulcer at the ileocolonic anastomosis. Patient 2
      had intestinal resection for strangulated internal hernia at 9 yr and was
      diagnosed with two ulcers at the ileoileal anastomosis at 14 yr of age. Fifteen
      patients with delayed anastomotic ulcers have so far been reported in the
      literature. We add two more cases and also emphasize the difficulty in
      establishing the diagnosis and importance of performing a retrograde ileoscopy.

PMID- 7733092
TI  - Delayed gastric emptying after laparoscopic anterior highly selective and
      posterior truncal vagotomy.
AB  - We describe a case of gastroparesis after laparoscopic highly selective anterior
      and posterior truncal vagotomy in a 30-yr-old male with gastric ulcer disease.
      Motility studies confirmed the diagnosis, and a pancreatic polypeptide sham
      feeding study suggested that a complete vagotomy may have been inadvertently
      performed. The experience with this procedure in gastric ulcer disease is
      extremely limited; review of the literature of laparoscopic highly selective
      vagotomy describes only two cases with delayed gastric emptying as defined by
      radiological examination. In view of the paucity of reports, caution is
      warranted, and this procedure should be undertaken only in the setting of a
      controlled trial.

PMID- 7733093
TI  - Heightened sensitivity of the esophagus to radiation in a patient with AIDS.
AB  - Esophageal stricture is an uncommon complication in HIV-negative patients treated
      with radiation to the chest for lung cancer. There have been a number of recent
      reports on the association of cancer and HIV-positive patients, as well as a
      greater sensitivity to radiation therapy of the mucous membranes in HIV/AIDS
      patients. This article reflects a review of the literature on the risk of major
      complications and morbidity of the esophagus in HIV+/AIDS patients whose chests
      are treated with radiation for lung cancer. Included is a report of a previously
      unpublished case of an early and severe esophageal reaction to radiation therapy
      in an AIDS patient.

PMID- 7733094
TI  - Double pylorus: report of a longitudinal follow-up in two refractory cases with
      underlying diseases.
AB  - Double pylorus is either a congenital abnormality or an acquired complication of
      peptic ulcer disease. We had followed two patients for 3 and 5 yr, respectively,
      to observe the processes of formation and the prognosis of double pylorus.
      Initially, duodenal ulcer was found in one patient with diabetes mellitus and
      chronic renal failure, and gastric ulcer was found in the other with chronic
      obstructive pulmonary disease. Both developed double pylorus with refractory
      courses. In spite of intensive medical treatment, both of them had persistent
      ulcers in the fistulous tract and failed to develop reepithelization.
      Helicobacter pylori was found in all of the specimens of gastroduodenal biopsies
      in both cases. Therefore, we believe that the refractory courses of double
      pylorus may be related to the underlying diseases and/or the presence of H.
      pylori. Antibacterial treatment of H. pylori or surgical intervention should be
      considered for patients with this condition.

PMID- 7733095
TI  - Somatostatinoma: atypical presentation of a rare pancreatic tumor.
AB  - Somatostatinomas are rare neuroendocrine tumors that can result in a variety of
      symptoms depending on the secretion of other peptides in association with or in
      response to somatostatin. The rarity and variable clinical presentation of these
      tumors present problems in diagnosis and management. This report details the
      treatment of a 66-yr-old male who had a somatostatinoma with an atypical location
      and presentation. His clinical course was one of recurrent disease treated
      surgically and the interval development of cholelithiasis. He has survived 5 yr
      with his tumor, illustrating that monitoring peptide levels and an aggressive
      surgical approach are warranted for this condition. Prophylactic cholecystectomy
      should be considered at the time of exploration.

PMID- 7733096
TI  - Torsade de pointes complicating the treatment of bleeding esophageal varices:
      association with neuroleptics, vasopressin, and electrolyte imbalance.
AB  - Torsade de pointes is an unusual life-threatening ventricular arrhythmia that has
      been associated with vasopressin, neuroleptic drugs, and electrolyte imbalances,
      including hypokalemia and hypomagnesemia. Over a 9-month period, we observed
      torsade de pointes in three patients with cirrhosis and bleeding esophageal
      varices who did not have prior cardiac disease. All had received endoscopic
      sclerotherapy and continuous infusions of vasopressin and nitroglycerin. For
      sedation, two patients received haloperidol and one droperidol. In addition, two
      patients had either hypokalemia or hypomagnesemia. In all three patients, there
      was prolongation of the electrocardiographic QT interval and a "long-short"
      initiating sequence followed by ventricular tachycardia with torsade de pointes
      morphology. All were successfully cardioverted; there was one late death due to
      aspiration and septicemia. We conclude that cirrhotics with variceal hemorrhage
      may be at increased risk of developing this arrhythmia in the setting of
      treatment with vasopressin, sedation with neuroleptic drugs, and electrolyte
      abnormalities. We urge close monitoring of these patients for cardiac arrhythmia
      and recommend that neuroleptics be used cautiously, if at all.

PMID- 7733097
TI  - Lupus anticoagulant masquerading as an acute abdomen with multiorgan involvement.
AB  - A 45-yr-old male patient developed acute abdominal pain, ileus, and microscopic
      hematuria with biochemical evidence of pancreatitis and a marked increase in
      liver alkaline phosphatase; CT demonstrated swelling of the pancreas, bilateral
      adrenal hemorrhage, and a suggestion of renal hemorrhage. ERCP was negative and
      renal arterial and venous blood flow normal. A coagulation profile demonstrated
      the presence of lupus anticoagulant, but tests for anticardiolipin antibodies and
      collagen vascular diseases were negative. Treatment with corticosteroids and
      anticoagulation resulted in improvement in clinical and all biochemical indices.
      Thus, lupus anticoagulant syndrome may masquerade as an acute abdominal illness
      with multiorgan involvement.

PMID- 7733098
TI  - Satisfactory outcome of percutaneous endoscopic gastrostomy in two patients with
      cirrhosis and portal hypertension.

PMID- 7733099
TI  - Portal venous gas as a complication of ERCP and endoscopic sphincterotomy.
AB  - We report a patient in whom portal venous gas occurred as a complication of
      endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy,
      presumably because of bleeding at the papilla that allowed gas to enter the
      duodenal wall and portal venous system. To our knowledge, four similar cases have
      been reported previously. Although these patients have had a benign clinical
      course with rapid resolution of the gas, they should be observed carefully for
      signs of duodenal bleeding or perforation.

PMID- 7733100
TI  - Generalized giant inflammatory polyposis in a patient with ulcerative colitis
      presenting with protein-losing enteropathy.

PMID- 7733101
TI  - Chaparral-induced hepatic injury.
AB  - Two patients with hepatic injury after ingestion of chaparral leaf are presented.
      The first patient, a 71-yr-old man, developed biopsy-proven hepatitis 3 months
      after ingesting chaparral leaf daily. His illness resolved with discontinuation
      of the herb and later recurred with rechallenge. The second patient is a 42-yr
      old woman who developed hepatitis 2 months after chaparral leaf ingestion and
      recovered completely after discontinuation of the compound. Both patients have
      remained well with abstinence from chaparral. These reports provide evidence of
      the hepatotoxicity of this herb and stress the need for awareness of the
      potential harm from such nonprescription remedies.

PMID- 7733102
TI  - Severe hepatocellular damage induced by chlormezanone overdose.
AB  - Chlormezanone is a widely prescribed muscle relaxant (1-3) whose pharmacology is
      well known (4-6), but the clinical effect of overdose still remains relatively
      obscure (1, 7, 8). We here report a recent case of a patient who had severe liver
      function impairment and other associated findings typical of chlormezanone
      overdose. The ingested dose (at least 12 g) is much larger than those of previous
      record (1, 2, 7, 8); thus, her critical presentation deserves to be reviewed.

PMID- 7733103
TI  - Chronic abdominal pain caused by thoracic disc herniation.
AB  - A patient with 7 yr of severe disabling chronic epigastric abdominal pain
      attributed to chronic pancreatitis was seen in consultation before a 95%
      pancreatectomy for pain control. Previous attempts to identify and treat the pain
      lead to extensive radiographic, pharmacological, endoscopic, and surgical
      interventions, including a Roux-en-Y pancreaticojejunostomy. Pain control was
      poor despite implantation of a continuous intrathecal morphine infusion pump. A
      focused physical examination, however, raised the suspicion of thoracic disc
      disease, which was confirmed after myelogram with computed tomography. Disruption
      of the T7-T8 disc with protrusion into the vertebral canal and displacement of
      the spinal cord with an associated bone spur were identified. A microsurgical
      thoracic discectomy was performed. Immediately, the pain began resolving, and she
      was pain free and off her medications within several weeks. To our knowledge,
      this is the first description of a herniated thoracic disc presenting as the pain
      of chronic pancreatitis. The diagnosis of thoracic disc syndrome requires a high
      index of suspicion and should be considered in patients with chronic abdominal
      pain.

PMID- 7733104
TI  - "I Can't Believe It's Not Butter": foreign body presenting as dysphagia.

PMID- 7733105
TI  - Endoscopic sphincterotomy really is safe.

PMID- 7733106
TI  - Men, women, and colorectal cancer: we are winning the battle.

PMID- 7733107
TI  - Another look at postpolypectomy hemorrhage.

PMID- 7733108
TI  - Once or twice daily doses of proton pump inhibitor in treating Barrett's
      esophagus?

PMID- 7733109
TI  - Effects of prostaglandins on esophageal mucosa: a new hypothesis.

PMID- 7733110
TI  - Chronic liver disease and lymphoma 10 years later.

PMID- 7733111
TI  - Neurobiology of functional bowel disorders in women with dysmenorrhea.

PMID- 7733112
TI  - Circadian distribution of acute bleedings from esophageal varices.

PMID- 7733113
TI  - Response to editorial by Drs. Ransahoff and Lang.

PMID- 7733114
TI  - Cholestatic reaction to warfarin.

PMID- 7733115
TI  - Treatment of acute severe exacerbation of chronic hepatitis B with cyclosporin A
      and interferon-beta: a case report.

PMID- 7733116
TI  - Endoscopic ultrasound in the diagnosis of gallbladder adhesions.

PMID- 7733117
TI  - Flow cytometry characterization of epithelial cells released in the watery stools
      of a patient with autoimmune enteropathy.

PMID- 7733118
TI  - Presentation of the 1995 Robert H. Williams Distinguished Chair of Medicine Award
      to William Nimmons Kelley, MD.

PMID- 7733119
TI  - New devices for coronary angioplasty: the emperor's new clothes revisited.

PMID- 7733120
TI  - Enalapril reduces the albuminuria of patients with sickle cell disease.
AB  - PURPOSE: To evaluate the effects of enalapril, an angiotensin-converting enzyme
      inhibitor, on albuminuria associated with sickle cell anemia. PATIENTS AND
      METHODS: Two males and 6 females, mean age 22.8 +/- 5.5 years, with sickle cell
      anemia and albuminuria, received enalapril for 6 months. Before entry into the
      study, all had a urinary albumin concentration above 30 mg/L as determined by
      radioimmunoassay documented on three separate occasions at intervals of 15 to 30
      days. Samples were collected before 10 AM after an oral water load of 10 mL/kg.
      RESULTS: Enalapril reduced 6 patients' pretreatment hyperalbuminuria to normal.
      One patient whose levels did not reach normal values experienced a reduction of
      70%. Fractional excretion of sodium, potassium, and lithium did not change during
      the treatment. Mean arterial pressure decreased by 8.6 +/- 0.42 mm Hg. Two years
      after enalapril was discontinued, there were no changes in sodium, potassium, or
      creatinine levels of 7 patients who had received enalapril or in their mean
      arterial pressures. Urinary albumin concentration increased relative to
      pretreatment levels in 2 individuals, returned to pretreatment levels in 2, and
      remained below 30 mg/L in 2. CONCLUSION: Our results demonstrate that enalapril
      reduces albuminuria in patients with sickle cell anemia. After discontinuation of
      the drug, however, the albuminuria may increase to pretreatment levels or higher.
      Whether the reduction in urinary albumin concentration by angiotensin-converting
      enzyme inhibitors can delay the development of progressive renal failure in
      sickle cell anemia patients remains to be established.

PMID- 7733121
TI  - Long-term observation of 208 adults with chronic idiopathic thrombocytopenic
      purpura.
AB  - PURPOSE: To define response to therapy and ultimate outcome of adults with
      idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: We
      retrospectively analyzed patients with ITP diagnosed between 1978 and 1988, and
      reexamined them between June 1992 and March 1993. Data from 208 cases were
      collected. Median patient age was 44 years (range 14 to 78) at the time of
      diagnosis, and 51 years (range 19 to 86) at reexamination. Length of follow-up
      ranged from 48 to 151 months (median 92) and was longer than 10 years in 26
      patients (12.5%). Reexamination included a careful interview, physical
      examination, complete blood count, screening for HIV infection, determination of
      platelet-bound IgG, and, in persistently thrombocytopenic patients, autoimmunity
      markers and routine laboratory investigations. RESULTS: A total of 121 patients
      with fewer than 50 x 10(9) platelets per liter received an initial treatment with
      prednisone (PDN) at a dosage of 1 mg/kg of body weight for 1 month. Refractory or
      relapsed cases underwent splenectomy and/or other therapeutic modalities. In 87
      patients with greater than 50 x 10(9) platelets per liter, no therapy was
      scheduled. An initial complete response to PDN was observed in 38.8% cases. A
      sustained complete remission (CR) lasting more than 6 months with no maintenance
      therapy was attained in 18.7%. At the time of last follow-up only 11 of these
      patients remained in CR. Sixty-three patients underwent splenectomy. Forty-seven
      (74.6%) had a CR, with 41 achieving a prolonged recovery (> 6 months). Twelve
      other cases attained a sustained partial remission. Long-lasting recoveries were
      observed in 7 other cases following alternative treatments. Spontaneous
      remissions occurred in 8 of 87 untreated cases after observation periods of 6
      months or more. Eleven deaths were recorded (6 women and 5 men, median age 73),
      but only 5 were attributable to thrombocytopenia. At last control, 43 patients
      were in complete remission and free from therapy, and 52 were still on therapy.
      Four thrombocytopenic patients had laboratory features and a clinical history
      consistent with an autoimmune disease. CONCLUSIONS: This analysis of ITP in
      adults suggests that splenectomy remains the most effective treatment. The
      majority of patients who undergo splenectomy can have a CR for many years, while
      only a minority of those who do not have this therapeutic modality or fail it are
      likely to attain similar results. The long-term prognosis of ITP is benign even
      in refractory cases. Spontaneous remissions can be observed in a significant
      percentage of untreated patients (about 9%). The development of overt autoimmune
      diseases is relatively uncommon. Particular attention should be given to the
      management of ITP in the elderly, where bleeding episodes of the central nervous
      system tend to occur more frequently.

PMID- 7733122
TI  - Multicenter, placebo-controlled trial comparing acarbose (BAY g 5421) with
      placebo, tolbutamide, and tolbutamide-plus-acarbose in non-insulin-dependent
      diabetes mellitus.
AB  - BACKGROUND: Acarbose delays release of glucose from complex carbohydrates and
      disaccharides by inhibiting intestinal alpha-glucosidases, thereby attenuating
      postprandial increments in blood glucose and insulin. This multicenter, double
      blind, placebo-controlled study compared the efficacy and safety of diet alone,
      acarbose, tolbutamide, and acarbose-plus-tolbutamide in non-insulin-dependent
      diabetes mellitus (NIDDM) patients. PATIENTS AND METHODS: A total of 290 patients
      with NIDDM and fasting plasma glucose levels of at least 140 mg/dL were
      randomized to receive treatment TID with acarbose 200 mg, tolbutamide 250 to
      1,000 mg, a combination of both drugs, or placebo. A 6-week run-in period was
      followed by double-blind treatment for 24 weeks, then a 6-week follow-up period.
      RESULTS: All active treatments were superior (P < 0.05) to placebo in reducing
      postprandial hyperglycemia and HbA1c levels. The ranking in order of efficacy
      was: acarbose-plus-tolbutamide, tolbutamide, acarbose, and placebo. The
      postprandial reductions in glucose were approximately 85 mg/dL for acarbose-plus
      tolbutamide, 71 mg/dL for tolbutamide, 56 mg/dL for acarbose, and 13 mg/dL for
      placebo. Tolbutamide was associated with increases in body weight and
      postprandial insulin levels when taken alone, but these were ameliorated when
      tolbutamide was taken in combination with acarbose. Acarbose alone or in
      combination with tolbutamide caused significantly more gastrointestinal adverse
      events (mainly flatulence and soft stools or diarrhea) than tolbutamide or
      placebo, but these were generally well tolerated. Clinically significant
      elevations in hepatic transaminase levels occurred in 3 patients in the acarbose
      group and 2 in the acarbose-plus-tolbutamide group. Transaminase levels returned
      to normal when therapy was discontinued. CONCLUSIONS: Acarbose was effective and
      well tolerated in the treatment of NIDDM. Control of glycemia was significantly
      better with acarbose compared with diet alone. Acarbose-plus-tolbutamide was
      superior to tolbutamide alone.

PMID- 7733123
TI  - A double-blind, placebo-controlled, dose-finding trial of intermittent nasal
      salmon calcitonin for prevention of postmenopausal lumbar spine bone loss.
AB  - PURPOSE: Nasal administration of salmon calcitonin (SCT) has been suggested for
      preventing trabecular bone loss during the first years following the menopause,
      but no conclusive evidence has appeared about the minimal effective dose. Since
      nasal calcitonin is highly expensive, it makes sense to define this dose.
      PATIENTS AND METHODS: We performed a double-blind, placebo-controlled,
      randomized, single-center study with a 3-arm parallel-group design. The subjects
      were 251 healthy women who had experienced natural menopause within the past 6 to
      72 months and were not affected by any diseases or treatments that interfere with
      calcium metabolism. They were randomly allocated in groups of 6 to receive
      intranasal SCT 50 IU (n = 84), SCT 200 IU (n = 84), or placebo (n = 83). All
      treatments were given on 5 consecutive days per week. Statistical analysis was
      based on two populations: intention-to-treat (IT) and valid completers (VC). The
      main assessments performed were bone mineral density of the lumbar spine (LSBMD)
      and biochemical parameters reflecting bone turnover (serum alkaline phosphatase,
      urinary calcium/creatinine, and hydroxyproline/creatinine ratios). RESULTS:
      Changes over the treatment period were comparable in the IT and VC populations.
      In the group receiving the placebo, LSBMD decreased from baseline to end point by
      a mean of 6.28% (95% confidence interval [CI] -7.69 to -4.89) in the IT
      population and 6.98% (95% CI -8.86 to -5.11) in the VC population (P = 0.0001,
      end LSBMD versus baseline LSBMD). LSBMD increased slightly with the 50-IU/d dose
      of SCT, by 0.82% (95% CI -0.26 to 1.89) in the IT population, and 0.51% (95% CI 
      0.69 to 1.72) in the VC (P = NS, versus baseline). Subjects who received SCT 200
      IU/d experienced significant increases of 2.03% (95% CI 0.92 to 3.15) in the IT
      population and 2.26% (95% CI 1.01 to 3.51) in the VC (both P = 0.001). The
      difference between the evolution of the combined groups receiving nasal SCT and
      the group treated with the placebo was highly significant (P = 0.0001). No
      significant changes were recorded in biochemical parameters reflecting bone
      turnover. CONCLUSIONS: SCT 50 IU/d administered nasally and intermittently
      appears to prevent lumbar bone loss in nonobese early postmenopausal women.

PMID- 7733124
TI  - Cyclical etidronate plus ergocalciferol prevents glucocorticoid-induced bone loss
      in postmenopausal women.
AB  - OBJECTIVE: To assess the benefit of cyclical etidronate plus ergocalciferol for
      the prevention of glucocorticoid-induced bone loss in a 2-year, prospective, open
      study based in an osteoporosis clinic. PATIENTS AND METHODS: Group 1 consisted of
      15 postmenopausal women (mean age 62.6 +/- 3.3 years) who commenced
      glucocorticoid therapy and were treated with cyclical etidronate (400 mg/d for
      the first month; thereafter, 400 mg/d for 2 weeks of every 3-month period),
      elemental calcium (1 g/d), and ergocalciferol (0.5 mg/wk). Group 2 consisted of
      11 postmenopausal women (mean age 60.2 +/- 4.7 years) with glucocorticoid-induced
      osteoporosis, who were attending the clinic at the same time and were treated
      with calcium supplements only (1 g/d). MEASUREMENTS: Lumbar spine and femoral
      neck bone mineral densities (BMD) were measured at baseline and after 12 and 24
      months of glucocorticoid therapy using a dual energy x-ray absorptiometer.
      RESULTS: The two groups did not differ with respect to age, years since the
      menopause, mean daily glucocorticoid dose, and baseline BMD values. During the
      first year of therapy, mean lumbar spine BMD increased from an initial value of
      0.88 g/cm2 to 0.94 g/cm2, an increase of 7% per year (95% confidence interval
      [CI] 3.7% to 10.2%; P < 0.001 compared with controls). Significant increases in
      BMD of 2.5% per year were also observed in the femoral neck (95% CI -1% to 6%; P
      < 0.01 compared with controls). After the second year of cyclical etidronate
      therapy, femoral neck BMD continued to increase (P < 0.05 compared with value at
      12 months), while lumbar spine BMD remained stable. CONCLUSION: Chronic
      glucocorticoid therapy may result in bone loss at most skeletal sites. Therapy
      with cyclical etidronate plus ergocalciferol not only prevented glucocorticoid
      induced bone loss, but even increased lumbar spine and femoral neck BMD in
      postmenopausal women commencing glucocorticoid therapy.

PMID- 7733125
TI  - Hemochromatosis screening in asymptomatic ambulatory men 30 years of age and
      older.
AB  - OBJECTIVE: To perform a cost-benefit analysis of screening for hereditary
      hemochromatosis. PATIENTS AND METHODS: A total of 3,977 consecutive men > or = 30
      years of age who presented for routine health checkups at a health maintenance
      organization medical center were screened for hereditary hemochromatosis by
      measuring transferrin saturation. Subjects with repeated transferrin saturation >
      or = 62% and ferritin level > or = 500 ng/mL (> or = 500 micrograms/L) were
      referred for liver biopsy. Subjects with transferrin saturation < 15% were
      referred for evaluation. Laboratory testing, screening, and abnormal screening
      test evaluation procedures were identified by chart review. RESULTS: Forty
      patients had transferrin saturation > or = 62%. One hundred seventy-two had
      transferrin saturation < 15%. Eight patients with hemochromatosis were
      identified. The 3 patients most seriously affected had hepatic iron
      concentrations > 250 mumol/g dry weight. Two of them had hepatic fibrosis. Seven
      cases of hemochromatosis were found among 1,974 white subjects who were screened.
      Only 1 case was found among the remaining subjects. CONCLUSIONS: Our observations
      support routine screening with transferrin saturation for white men > or = 30
      years of age.

PMID- 7733126
TI  - Enhanced serum levels of thiobarbituric-acid-reactive substances in diabetes
      mellitus.
AB  - PURPOSE: To investigate whether serum levels of lipid peroxides measured as
      thiobarbituric-acid-reactive substances (TBARS) differ in type I and type II
      diabetic patients, whether serum levels correlate with late sequelae of diabetes,
      and whether serum levels of free vitamin E correlate with levels of lipid
      peroxidation by-products. PATIENTS AND METHODS: The relationship among lipids,
      glycosylated hemoglobin A1c (HbA1c), lipid peroxides measured as TBARS, and free
      vitamin E was determined in 158 patients. Fifteen of the 77 patients with type I
      diabetes and 39 of the 81 patients with type II diabetes had clinically apparent
      peripheral vascular disease or coronary artery disease, or both. RESULTS:
      Compared with control subjects, serum levels of TBARS were found to be
      significantly elevated (P < 0.001) in diabetic patients, and type II diabetic
      patients had significantly higher levels (P < 0.001) than type I patients. Both
      type I and type II diabetic patients with good metabolic control (HbA1c < 6.5%)
      had significantly lower (P < 0.005) TBARS levels than patients with poor
      metabolic control, but all groups had higher levels than the control group. Type
      II patients with angiopathy had significantly higher levels of TBARS than
      patients without angiopathy. Free vitamin E levels in control subjects and
      diabetic patients did not differ statistically. CONCLUSION: Serum levels of TBARS
      were significantly increased in all patients suffering from diabetes mellitus,
      whereby TBARS levels did not depend on the total amount of circulating lipids. It
      can be suggested that the enhanced lipidperoxidation is contributed to an
      increased formation of free radicals in diabetes mellitus.

PMID- 7733127
TI  - The natural history of atrial fibrillation: incidence, risk factors, and
      prognosis in the Manitoba Follow-Up Study.
AB  - PURPOSE: Atrial fibrillation is a common arrhythmia associated with increased
      cardiovascular morbidity and mortality. This study was undertaken to identify the
      natural history of this condition, including risk factors for its development,
      and outcome. PATIENTS AND METHODS: The incidence of atrial fibrillation among
      3,983 male air crew recruits observed continuously for 44 years was calculated
      based on person-years of observation. Age and 23 variables were examined to
      identify risk factors for atrial fibrillation. Controlling for age and 9
      prognostic variables, the effect of atrial fibrillation on 8 outcomes was
      examined. Analysis of risk factors for atrial fibrillation and outcome after
      atrial fibrillation was based on a Cox proportional hazard model using time
      dependent covariates. RESULTS: Of the 3,983 study members, 299 (7.5%) developed
      atrial fibrillation during 154,131 person-years of observation. The incidence
      rose with age from less than 0.5 per 1,000 person-years before age 50 to 9.7 per
      1,000 person-years after age 70. Risk for atrial fibrillation was increased with
      myocardial infarction (relative risk [RR] 3.62), angina (RR 2.84), and ST-T wave
      abnormalities in the absence of ischemic heart disease (RR 2.21). The RR for
      atrial fibrillation was strongest at the onset of ischemic heart disease and
      diminished over time. The rate of atrial fibrillation was 1.42 times increased in
      men with a history of hypertension. Congestive heart failure, valvular heart
      disease, and cardiomyopathy were important but uncommon risk factors. Atrial
      fibrillation independently increased the risk for stroke (RR 2.07) and congestive
      heart failure (RR 2.98). Total mortality rate was increased 1.31 times;
      cardiovascular mortality including and excluding fatal stroke were also increased
      (RR 1.41 and 1.37, respectively). CONCLUSIONS: The incidence of atrial
      fibrillation in men increases with advancing age. Clinical cardiac abnormalities,
      particularly recent ischemic heart disease and hypertension, are strongly
      associated with increased risk for atrial fibrillation. Atrial fibrillation
      increases morbidity and mortality, but the magnitude of the increase may be less
      than previously reported.

PMID- 7733128
TI  - Improved left ventricular function after thiamine supplementation in patients
      with congestive heart failure receiving long-term furosemide therapy.
AB  - PURPOSE: We have previously found thiamine (vitamin B1) deficiency in patients
      with congestive heart failure (CHF) who had received long-term furosemide
      therapy. In the present study, we assessed the effect of thiamine repletion on
      thiamine status, functional capacity, and left ventricular ejection fraction
      (LVEF) in patients with moderate to severe CHF who had received furosemide in
      doses of 80 mg/d or more for at least 3 months. PATIENTS AND METHODS: Thirty
      patients were randomized to 1 week of double-blind inpatient therapy with either
      i.v. thiamine 200 mg/d or placebo (n = 15 each). All previous drugs were
      continued. Following discharge, all 30 patients received oral thiamine 200 mg/d
      as outpatients for 6 weeks. Thiamine status was determined by the erythrocyte
      thiamine-pyrophosphate effect (TPPE). LVEF was determined by echocardiography.
      RESULTS: TPPE, diuresis, and LVEF were unchanged with i.v. placebo. After i.v.
      thiamine, TPPE decreased (11.7% +/- 6.5% to 5.4% +/- 3.2%; P < 0.01). LVEF
      increased (0.28 +/- 0.11 to 0.32 +/- 0.09; P < 0.05), as did diuresis (1,731 +/-
      800 mL/d to 2,389 +/- 752 mL/d; P < 0.02), and sodium excretion (84 +/- 52 mEq/d
      to 116 +/- 83 mEq/d, P < 0.05). In the 27 patients completing the full 7-week
      intervention, LVEF rose by 22% (0.27 +/- 0.10 to 0.33 +/- 0.11, P < 0.01).
      CONCLUSIONS: Thiamine repletion can improve left ventricular function and
      biochemical evidence of thiamine deficiency in some patients with moderate-to
      severe CHF who are receiving longterm furosemide therapy.

PMID- 7733129
TI  - Is obesity a barrier to physician screening for cervical cancer?
AB  - OBJECTIVE: To determine if obese and morbidly obese women are as likely to
      receive Papanicolaou (Pap) smears as nonobese women. PATIENTS AND METHODS: A
      secondary analysis was conducted of data collected during a prospective,
      controlled trial of computer-generated reminders to improve preventive care. The
      site was a large, academic general medicine practice providing primary care to an
      urban population at a university-affiliated municipal teaching hospital. Data
      were analyzed from 15 faculty and 77 resident physicians who delivered care to
      1,321 women who were eligible for Pap smears. Patient data were obtained from a
      computerized medical record system. RESULTS: Outcomes were physician reports of
      Pap smear performance and reasons for nonperformance of Pap smears in eligible
      women. Pap smear performance was 21% for nonobese women, 20% for obese women, and
      20% for morbidly obese women (P = NS). After adjusting for age and race, odds
      ratios for omission of Pap smear were 1.20 for both obese (95% confidence
      interval [CI] 0.86 to 1.67; P = NS) and morbidly obese women (95% CI, 0.58 to
      2.47; P = NS). A significant dose-response relationship was found between
      increasing patient weight and physician responses that the Pap smear was delayed
      due to patient's acute illness, vaginitis, or menstruation (odds ratios [OR] 1.73
      for obese, OR 4.59 for morbidly obese women; P < 0.005). CONCLUSIONS: In our
      general medicine practice, obesity does not appear to be associated with less Pap
      smear performance. Physicians are more likely to report delaying obese patients'
      Pap smears due to acute illness, vaginitis, or menstruation.

PMID- 7733130
TI  - Fever, chest pain, and a dilated aortic root in a 27-year-old man.

PMID- 7733131
TI  - Innocent bystander.

PMID- 7733132
TI  - Nondilated obstructive uropathy due to a ureteral calculus.

PMID- 7733133
TI  - Trousseau's syndrome with nonbacterial thrombotic endocarditis: pathogenic role
      of antiphospholipid syndrome.

PMID- 7733134
TI  - Urinary methylmalonic acid and cobalamin deficiency in the elderly.

PMID- 7733135
TI  - More on HDL subfractions.

PMID- 7733136
TI  - Patient age as a determinant of housestaff time allocation.

PMID- 7733137
TI  - Hypocholesterolemia and human immunodeficiency virus-1 (HIV-1) infection.

PMID- 7733138
TI  - Hypocholesterolemia and human immunodeficiency virus-1 (HIV-1) infection.

PMID- 7733139
TI  - Research and health care reform.

PMID- 7733140
TI  - Human hematopoietic stem cells: potential use as tumor-free autografts after high
      dose myeloablative cancer therapy.
AB  - Human hematopoietic stem cells are rare cells residing within the marrow and
      peripheral blood of humans. These cells are capable of producing each of the
      myeloid and lymphoid cell types and have the ability to produce additional stem
      cells. The infusion of stem cells in a graft is responsible for hematopoietic
      reconstitution after the delivery of lethal irradiation and/or high dose
      chemotherapy. Stem cells have been extensively characterized, and their phenotype
      has been defined. Technologies have now been developed that permit the isolation
      of sufficient numbers of stem cells for their use as grafts during hematopoietic
      cell transplantation. Mobilized peripheral blood grafts obtained from patients
      with cancer are frequently contaminated with tumor cells. The isolation of stem
      cells from mobilized peripheral blood permits the creation of a potentially free
      tumor-free graft. Such tumor free autografts might prevent the infusion of tumor
      cells receiving curative myeloablative therapies and thereby improve the efficacy
      of autotransplantation strategies for patients with selected cancers.

PMID- 7733141
TI  - The homing of hematopoietic stem cells to the bone marrow.
AB  - In this article, the author discusses some of the most notable aspects of the
      work of Mehdi Tavassoli and others on the homing of intravenously transplanted
      hematopoietic stem cells to the marrow. It is well-recognized that homing of stem
      cells is a highly selective process, perhaps similar to the homing of lymphocytes
      to lymphoid tissues. The nature of the selectivity of stem cell homing is
      unclear, however, and may be mediated through a specific homing receptor or
      through a method of selective capture, retainment, or survival advantage afforded
      by the marrow. In this article, the focus is on current research in the
      identification of a specific homing receptor, the potential regulation of such a
      receptor by cytokines, the homing phenomenon as a multi-step process, and
      secondary adhesive interactions mediated by known adhesive molecules. These
      interactions may serve to strengthen the initial recognition and engraftment of
      stem cells within the hematopoietic compartment of the marrow.

PMID- 7733142
TI  - Case report: fulminant Kaposi's sarcoma after orthotopic liver transplantation.
AB  - Fulminant multicentric Kaposi's sarcoma developed in an American-born HIV
      negative patient 8 months after orthotopic liver transplantation. Despite its
      rarity in liver transplantation, Kaposi's sarcoma should be considered in the
      differential diagnosis in hepatic allograft recipients presenting with rapidly
      growing cutaneous or polylymphadenopathic lesions.

PMID- 7733143
TI  - Case report: the first report of idiopathic hypereosinophilic syndrome involved
      with lung and middle ear.
AB  - It has been reported that various organs are involved in idiopathic
      hypereosinophilic syndrome. Frequently, the heart, lung, skin, and nervous system
      are involved. Involvement of the middle ear, however, has not yet been reported.
      In this article, the authors describe the first case of hypereosinophilic
      syndrome involving the lung and middle ear. A 39-year-old woman had a 4-month
      history of low grade fever, non-productive cough, and a feeling of fullness and
      hearing loss in both ears. Peripheral blood cell count showed eosinophilia.
      Bilateral tympanic cavities were obstructed with granulation tissue, and she was
      diagnosed as obliterative otitis media. The granulation tissue consisted of foamy
      histiocytes and eosinophils. Chest X-ray film and computed tomography showed
      patchy infiltrative shadow in the lung. Histologic examination of the open lung
      biopsied specimen showed alveolar spaces infiltrated by eosinophils. After
      treatment with 30 mg oral prednisolone daily, there was a rapid improvement in
      her clinical condition. Based on the clinical course and the histologic findings
      of this case, obliterative otitis media may be caused by eosinophilic
      infiltration and eosinophilic pneumonia.

PMID- 7733144
TI  - Southwestern Internal Medicine Conference: high-dose intravenous gamma globulin
      therapy: how does it work?
AB  - In the past, IgG replacement has been used primarily to treat patients with
      hypoglobulinemia or agammaglobulinemia. With the availability of preparations of
      IgG suitable for intravenous use (IVIG), much higher doses may now be given
      safely. Surprisingly, administration of very high doses of IVIG in several
      immunologically related diseases have produced improvement not achieved by other
      means of therapy. The mechanisms by which IVIG causes these diseases to improve
      vary with the immunopathogenesis of each disease. Provision of antibodies
      otherwise unavailable to a given patient, IgG-Fc-receptor blockade, modification
      of complement activation and modulation of the immune response by anti-idiotypic
      antibodies are discussed as mechanisms of action of IVIG. Because of the expense
      and relative scarcity of large amounts of purified, pooled normal IgG, this form
      of therapy should be used only for selected illnesses for which other treatment
      is ineffective.

PMID- 7733145
TI  - Body composition in hemodialysis patients measured by dual-energy X-ray
      absorptiometry.
AB  - Dual-energy X-ray absorptiometry (DXA) measures three of the principal components
      of the body: fat mass, lean soft-tissue mass (comprising muscle, inner organs,
      and the body water), and the bone mineral content. The purpose of this study was
      to test the estimation capacity of DXA when it is applied to patients with end
      stage renal failure. Twenty dialysis patients were examined by DXA before and
      after one hemodialysis session. A highly significant positive correlation between
      weight measurements performed by conventional scales and DXA was found. A
      positive correlation between fluid loss during dialysis and reduction in fat-free
      mass (lean soft-tissue mass plus bone mineral content) was observed by DXA. The
      estimation of the fat-free mass was independent of the amount of fluid loss. No
      significant differences in variance between the data obtained before and after
      the dialysis were observed. We conclude that DXA is a useful tool for estimating
      the magnitude of body compartments in patients with end-stage renal failure.

PMID- 7733146
TI  - Interstitial myofibroblasts in IgA glomerulonephritis.
AB  - We examined renal biopsy specimens from patients with mesangial IgA
      glomerulonephritis (n = 25; plasma creatinine 0.05-0.30 mmol/l) to ascertain
      whether the myofibroblast has a role in progressive renal interstitial fibrosis.
      Myofibroblasts were identified by morphology and alpha smooth muscle actin (alpha
      SMA) immunostaining at the light and electron microscope level. Results were
      related to staining for interstitial leukocytes and collagen III. A control group
      consisted of 6 normal renal transplant donors from whom biopsy specimens were
      taken at the time of vascular anastomosis. The fractional volume of interstitial
      alpha-SMA staining was greater in patients with mesangial IgA glomerulonephritis
      than in the control group (17.2 vs. 1.3%; p < 0.001). alpha-SMA staining was
      increased in areas of interstitial fibrosis with prominent periglomerular and
      peritubular distribution. Ultrastructural studies established that alpha-SMA
      staining in the renal interstitium was intracellular, cytoplasmic, and confined
      to myofibroblast-like cells and processes. The alpha-SMA expression correlated
      with fractional volume of tubular atrophy/dilation (r = 0.79, p < 0.001),
      interstitial connective tissue (r = 0.66, p < 0.001), leucocytes (r = 0.72, p <
      0.005), and collagen III (r = 0.71, p < 0.001). Staining correlated with renal
      function at the time of biopsy (r = 0.64, p < 0.005) and after 2 years of follow
      up (r = 0.77, p < 0.01). In conclusion, cells with a myofibroblast-like phenotype
      have a significant role in the progression of tubulointerstitial injury.

PMID- 7733147
TI  - Relationship of body iron status and serum aluminum in chronic renal
      insufficiency patients not taking any aluminum-containing drugs.
AB  - The present study examines the serum aluminum (Al) and daily urine Al excretion
      in 50 patients with chronic renal insufficiency (CRI) who are not taking any Al
      containing agents. The influence of body iron stores and hematological indexes on
      the above parameters were also studied. Data on a group of 20 healthy subjects
      not taking any drugs were included for comparisons. The basal Al levels in CRI
      patients (10.5 +/- 9.7 micrograms/l) were significantly higher than those (3.8 +/
      2.4 micrograms/l) of the normal subjects. In addition, the renal Al clearance
      (2.98 +/- 0.35 ml/min) in CRI patients was significantly lower than that (4.93 +/
      0.21 ml/min) in normal subjects. Although all serum Al levels of our patients
      were within the nontoxic range (< 50 micrograms/l), the results of our study
      showed a negative correlation between serum Al and serum transferrin saturation
      (r = -0.40, p < 0.005) as well as serum iron (r = -0.406, p < 0.005). There was a
      negative correlation between daily urine Al excretion and serum ferritin levels
      (r = -0.305, p = 0.031). The study group is further divided into 2 subgroups,
      i.e. group A (ferritin < 100 micrograms/l) and group B (ferritin > 300
      micrograms/l). The daily urine Al excretion in group A was higher than that in
      group B. In conclusion, our study first demonstrates that Al tends to be
      accumulated in patients with CRI, similar to Al in patients with hemodialysis,
      and the chronic low-level Al exposure in CRI patients may affect body iron status
      and metabolism, or iron status may play a role in Al absorption and
      excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733148
TI  - Renal transplantation in systemic lupus erythematosus: a single-center experience
      with sixty-four cases.
AB  - The outcome of renal transplantation in 64 patients with end-stage renal disease
      (ESRD) secondary to lupus nephritis is the subject of this report. The patients
      were transplanted over a 150-month (12.5-year) period (between July 5, 1979, and
      January 30, 1992). The study population is predominantly made up of young females
      (mean age, 34.7 +/- 9 years, n = 54, 81.3%). Fifty-one transplants (79.7%) are
      cadaveric, and 13 (20.3%) are from living-related donors. Fifty-eight patients
      (90.6%) had primary (first) allografts, and 6 (9.4%) received a second allograft.
      Posttransplantation immunosuppression consisted of azathioprine and prednisone
      (AZA group, n = 22, 34.3%) or AZA, prednisone and cyclosporine (CsA group, n =
      42, 65.6%). For all 64 patients combined, the 1-year graft and patient survival
      rates are 68.8 and 86.5%, respectively, whereas 5-year graft and patient survival
      rates are 60.9 and 85.9%, respectively. Patients whose immunosuppressive regimen
      was CsA-based had a 1-year graft survival of 71.5 versus 63.6% in the AZA group.
      However, this 7.9% difference did not reach statistical significance (p = 0.95).
      The 5-year graft survival of the CsA-based group was 69.1 versus 45.5% for the
      AZA group, p < 0.05. One-year patient survival was 77.3% for the AZA group and
      92.9% for the CsA group, p < 0.05). The data show that patients with ESRD
      secondary to lupus nephritis can undergo renal transplantation with satisfactory
      outcome. Immunosuppression based upon CsA improves first-year patient and
      allograft survival by 15.6 and 7.9%. respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7733149
TI  - Prevention of cardiac hypertrophy in experimental chronic renal failure by long
      term ACE inhibitor administration: potential role of lysosomal proteinases.
AB  - The pathogenesis of cardiac hypertrophy in chronic uremia is poorly understood.
      In the present study, the long-term effects of chronic uremia on cardiac
      morphology and various cysteine proteinases of the heart were investigated in
      rats with and without antihypertensive therapy by the angiotensin converting
      enzyme inhibitor enalapril or by the calcium channel blocker verapamil. 16 weeks
      after subtotal nephrectomy considerable uremia had developed associated with
      arterial hypertension, rise in heart weight and heart weight/body weight ratio.
      Morphologically myocardial cells developed marked hypertrophy. Determination of
      various cysteine proteinases by fluorometry revealed a significant decline of
      cathepsin B activity while the activities of cathepsin H and L were unchanged.
      Antihypertensive treatment with enalapril and verapamil normalized the blood
      pressure and improved renal function significantly. Myocardial cell hypertrophy
      and the enhanced heart weight/body weight ratio were normalized under treatment
      with enalapril but not with verapamil. Simultaneously, the impaired cathepsin B
      activity returned to the normal range after enalapril treatment. It is concluded
      that the cardiac hypertrophy in uremia is at least partly caused by an activation
      of the circulating and/or cardiac renin-angiotensin system. Impaired proteinase
      activity in the uremic state may be involved in the development of cardiac
      hypertrophy.

PMID- 7733150
TI  - Immunological aspects of a case of posttransplant lymphoproliferative disorder.
AB  - We describe a female renal transplant recipient with cytomegalovirus and Epstein
      Barr virus (EBV) infections who developed aggressive polymorphous polyclonal B
      cell proliferation. She received two courses of OKT3. We found a majority of
      transformed B cells bearing EBV membrane receptor CR2 and EBV nuclear antigen.
      Posttransplant lymphoproliferative disorders may be associated with a significant
      immunological activation, detected in this case by the sudden increase of beta 2
      microglobulin and immunoglobulin levels, including immunoglobulin D. These raised
      levels persisted throughout the short and rapid course of the disease.

PMID- 7733151
TI  - End-stage renal failure from renal amyloidosis of the AA type associated with
      giant lymph node hyperplasia (Castleman's disease).
AB  - A case of end-stage renal failure caused by renal amyloidosis of the AA type is
      reported. No chronic disease responsible for the deposition of reactive amyloid
      was detected until giant lymph node hyperplasia of the angiofollicular type was
      identified in a mediastinal mass. Amyloid was found within the tumour mass and
      was characterized by immunochemistry with monoclonal antibodies to be of the AA
      type. Castleman's disease should be added to the list of chronic diseases
      endangering renal function by inducing the production and tissue deposition of
      secondary (AA) amyloid.

PMID- 7733152
TI  - Diagnostic considerations in pheochromocytoma and chronic hemodialysis: case
      report and review of the literature.
AB  - We present a patient on long-term hemodialysis (LTH) discovered to have a
      pheochromocytoma. A thorough workup pertaining his catecholamine status was
      performed, and intraoperative catecholamine changes were monitored. This
      condition poses some analytical difficulties as both interpretation of plasma
      catecholamine measurements and determination of their metabolic products are
      impaired. The literature about catecholamines with respect to hemodialysis is
      reviewed, and the known cases of pheochromocytoma in LTH patients are discussed.
      Predialysis norepinephrine concentrations were almost consistently elevated
      though less than 3-fold when compared to normal controls. Epinephrine is not
      significantly different in both groups. At least a 3.3-fold increase of
      epinephrine or norepinephrine in LTH patients with adrenal pheochromocytomas is
      observed. We conclude that plasma epinephrine elevations can be evaluated in the
      conventional manner, and norepinephrine concentrations beyond a 3-fold elevation
      should raise the suspicion of a pathological catechol excess syndrome. The
      interpretation of plasma homovanillic acid and vanillylmandelic acid in this
      condition is complicated by the lack of data in LTH patients without
      pheochromocytoma. Markedly elevated baseline concentrations for these parameters
      are assumed.

PMID- 7733153
TI  - Penectomy in diabetic patients undergoing maintenance dialysis.
AB  - Penectomy was performed to sustain life in 2 patients with insulin-dependent and
      non-insulin-dependent diabetes mellitus, respectively, who were undergoing
      maintenance hemodialysis. Both patients previously had manifested a series of
      serious macro- and microvascular diabetic complications. The histopathologic
      findings in both cases included gangrenous necrosis of penile tissue, while case
      2 also evinced calcification of penile arteries. Penectomy has been reported as
      the result of penile malignancy, anticoagulant toxicity, self-inflicted injury,
      and criminal assault. Other reports document penectomies attributed to perineal
      infection (Fournier's syndrome) in diabetic patients with uremia. In five
      previously reported cases of penectomy in diabetic patients undergoing dialysis,
      systemwide arteriopathy was present in all. There is an association between
      uremia in diabetics and predisposition to an ischemic-infectious lesion of the
      penis that fails to respond to antimicrobial therapy.

PMID- 7733154
TI  - Lupus anticoagulant in anti-neutrophil cytoplasmic antibody-associated
      polyarteritis.
AB  - Lupus anticoagulant has been described in association with many autoimmune
      disorders. Here we describe its occurrence in a patient with ANCA-associated
      microscopic polyarteritis with medium vessel involvement. A 62-year-old man
      presented with mononeuritis multiplex and abdominal pain and was demonstrated to
      have multiple aneurysms on visceral angiography, consistent with the diagnosis of
      medium vessel vasculitis or classical polyarteritis nodosa. In addition he had
      active tuberculosis. He developed a deep venous thrombosis at this admission and,
      on one occasion, had a prolonged APTT but this was not confirmed to be due to a
      lupus anticoagulant. Two years later when the patient was readmitted with fevers,
      headaches and nasal discharge, both ANCA and a lupus anticoagulant were
      demonstrated in his serum, although there was no evidence of a venous thrombosis.
      Six months later the patient was demonstrated for the first time to have
      dysmorphic urinary RBC consistent with glomerular bleeding; at the same time he
      developed a deep venous thrombosis. ANCA was still present, but the lupus
      anticoagulant could not be detected. The patient was treated with
      cyclophosphamide and prednisolone and a Greenfield filter inserted into his
      inferior vena cava.

PMID- 7733155
TI  - IgA nephropathy associated with Takayasu's arteritis: report of a case and review
      of the literature.
AB  - We report the case of a patient with Takayasu's arteritis, nephrotic syndrome,
      and pANCA. The kidney biopsy specimen showed the classic features of IgA
      nephropathy. The course of this patient supports the view that the glomerular and
      vasculitic involvements of Takayasu's arteritis may result from a common
      immunologic mechanism, and cases with urinary abnormalities should be carefully
      followed for the possible coexistence of glomerulonephritis.

PMID- 7733156
TI  - Escape of red blood cells through gaps in glomerular basement membrane in a
      patient with mixed connective tissue disease.
AB  - Hematuria in patients with glomerulonephritis seems to result from the passage of
      red blood cells through anatomical gaps in the glomerular basement membrane.
      However, such morphological evidence has rarely been demonstrated. A patient with
      mixed connective tissue disease associated with membranous glomerulonephritis is
      described in whom the renal biopsy specimen showed an escape of red blood cells
      through a gap in the basement membrane. These findings support the morphological
      basis of hematuria in glomerulonephritis.

PMID- 7733157
TI  - Bilateral emphysematous pyelonephritis responding to nonsurgical management.
AB  - Bilateral emphysematous pyelonephritis is a rare condition, with only 14 cases
      reported in the English literature. It carries a bad prognosis, surgical
      management being the recommended mode of therapy. We report a case of bilateral
      emphysematous pyelonephritis in a 50-year-old diabetic lady which was
      successfully managed using antibiotics alone.

PMID- 7733158
TI  - Pharmacokinetics of recombinant leukocyte interferon in a patient on continuous
      ambulatory peritoneal dialysis.

PMID- 7733159
TI  - Renal perfusion in developing focal-segmental glomerulosclerosis: a hypothesis.

PMID- 7733160
TI  - Hemorrhagic bullae as a complication of urokinase therapy for hemodialysis
      catheter thrombosis.

PMID- 7733161
TI  - Imipenem/cilastatin in the treatment of CAPD peritonitis.

PMID- 7733162
TI  - Glomerular vascular resistance to blood flow: a brief review.
AB  - It is accepted that glomerular vascular resistance to blood flow is represented
      by a pressure drop of only a few mm Hg, but the hemodynamic basis for this
      concept is generally not well known. Our purpose is to review the evidence
      supporting the low resistance concept and to provide an explanation based on the
      fact that the glomerular network consists of 20-40 capillary loops placed 'in
      parallel' which markedly reduce the viscous resistance to flow (analogous to
      electrical circuits). A low pressure drop in the glomerular capillaries would be
      significant in filtration function.

PMID- 7733163
TI  - Glomerular morphometry of twenty-three biopsied patients with IgA nephropathy.
AB  - The aim of the present study was the process of an easy method for quantitative
      evaluation of the alterations of the mesangial matrix, cellularity and urinary
      space in IgA glomerulonephritis (IgA-GN) by the image analysis technique. A Vidas
      (Kontron-Zeiss) image analyzer was employed for the morphometric study of renal
      biopsies from 23 patients with IgA-GN. The following parameters were assessed:
      mesangial matrix index, expressed as the ratio between mesangial area and total
      glomerular area x 100; mesangial cellularity index, considered as the ratio
      between the total number of nuclei contained in the glomerulus and the overall
      glomerular area in mm2 x 10(4); urinary space/glomerular area ratio. The
      morphometric results compared to the respective values observed in normal
      glomeruli indicate an increase in the overall area of glomeruli with IgA-GN and,
      conversely, a decrease in the total area occupied by the urinary space (p =
      0.0001). It can therefore be concluded that the morphometric determination of the
      morphologic abnormalities occurring in the renal glomerulus with IgA-GN is an
      extremely useful method to describe the characteristics of this pathologic
      condition with a rapid and less laborious approach.

PMID- 7733165
TI  - Antidepressant drugs: disservice to elders?

PMID- 7733164
TI  - Med errors: the new antihistamines.

PMID- 7733166
TI  - Silicone revisited.

PMID- 7733167
TI  - Keep the story alive.

PMID- 7733168
TI  - Abdominal aortic aneurysm: warning flags to watch for.

PMID- 7733169
TI  - Olga's reason to live.

PMID- 7733170
TI  - Clinical snapshot: congestive heart failure.

PMID- 7733171
TI  - Wound care: how to use the red-yellow-black system.

PMID- 7733172
TI  - AJN Interview Hermina Bartkowski. Interview by Marietta Lee.

PMID- 7733173
TI  - Ten tips for safer suctioning.

PMID- 7733174
TI  - Emergency! Pediatric head trauma.

PMID- 7733175
TI  - Respite for the caregiver.

PMID- 7733176
TI  - Dealing with death: 'I want to see my son'.

PMID- 7733177
TI  - Seven steps to successful decision-making.

PMID- 7733178
TI  - State of the profession, Day of the Nurse 1995.

PMID- 7733179
TI  - Ginger-Sweet.

PMID- 7733180
TI  - Retinal photoreceptor dystrophies LI. Edward Jackson Memorial Lecture.
AB  - PURPOSE: To assess the state of knowledge of photoreceptor dystrophies. METHODS:
      The current literature concerning photoreceptor dystrophies is reviewed, and
      their potential impact on concepts of pathogenesis of disease and clinical
      practice is assessed. RESULTS: As a result of cooperative investigative work
      between researchers in various disciplines, major advances in the classification
      of retinal photoreceptor dystrophies have been made. Until recently,
      classification of retinal dystrophies was based on clinical observation alone,
      and it was evident that this method was imprecise and of limited value. Largely
      through the work of molecular biologists, it has been shown that diseases
      clinically indistinguishable from one another may be a result of mutations on a
      variety of genes; conversely, different mutations on a single gene may give rise
      to a variety of phenotypes. It is reassuring that it is possible to generate
      concepts as to potential pathogenetic mechanisms that exist in retinal
      dystrophies in light of this new knowledge. More important for the clinician is
      the potential impact on clinical practice. There is as yet no therapy by which
      the course of most of these disorders can be modified. However, there is a
      considerable body of work in which therapeutic intervention is being explored,
      and many researchers now see treatment as a justifiable objective of their work.
      CONCLUSIONS: Knowledge of the causative mutation is of value to the clinician in
      that it provides a precise diagnosis and allows the distribution of the abnormal
      gene to be documented fully within a family. To take full advantage of the
      opportunities provided by current research, clinical practice will have to be
      modified, particularly if therapy can be justified.

PMID- 7733181
TI  - Vitrectomy for proliferative diabetic retinopathy with severe equatorial
      fibrovascular proliferation.
AB  - PURPOSE: We studied the surgical treatment and visual outcome in a consecutive
      series of eyes with an unusual syndrome of diabetic retinopathy and severe
      peripheral fibrovascular proliferation involving the equatorial and pre
      equatorial fundus. METHODS: In a retrospective study of 276 eyes (245 patients)
      that underwent pars plana vitrectomy for diabetic retinopathy between November
      1988 and February 1993, nine eyes of eight patients (3.3% of eyes and 3.3% of
      patients) had severe equatorial fibrovascular proliferation. The condition
      occurred primarily in previously unoperated-on eyes (except for panretinal
      photocoagulation) and resulted in peripheral traction or traction-rhegmatogenous
      retinal detachment (six eyes), severe vitreous hemorrhage (two eyes), and severe
      hypotony (one eye). Relief of traction from peripheral fibrovascular membranes
      was obtained with an encircling scleral buckle (nine eyes) and limited
      delamination and segmentation (five eyes) or relaxing retinectomy (two eyes).
      Lensectomy was required for adequate membrane dissection in three eyes. RESULTS:
      After follow-up of six to 52 months (mean, 20.4 months), the visual acuity was
      20/200 or better in seven of nine eyes, with complete retinal attachment in seven
      of nine eyes and postequatorial attachment in all eyes (100%). Poor outcome
      resulted from a persistent response resembling Coats' disease in one eye and
      preexistent long-standing retinal detachment in one eye. CONCLUSIONS: Vitrectomy
      for severe equatorial fibrovascular proliferation differs from conventional
      approaches to diabetic retinopathy in that relief of retinal traction must be
      attained by scleral buckling and adequate dissection of peripheral fibrovascular
      tissue. In advanced cases, lensectomy and relaxing retinotomy may be required.

PMID- 7733182
TI  - Prognosis of stage 2 macular holes.
AB  - PURPOSE: We ascertained the natural course of stage 2 idiopathic macular holes to
      determine better treatment possibilities. METHODS: We reviewed 48 eyes with stage
      2 idiopathic macular holes and followed them up for more than two years. At each
      examination, best-corrected Snellen visual acuity was measured by a physician
      masked to the hypothesis of the study. RESULTS: Stage 2 lesions progressed to
      stage 3 or 4 during the follow-up period in 32 (67%) and 14 (29%) of 48 eyes,
      respectively; two eyes (4%) remained in stage 2. In 41 (85%) of 48 eyes, the hole
      size enlarged during the follow-up: 32 (94%) of 34 eyes had vitreomacular
      attachment and nine (64%) of 14 eyes had vitreomacular separation at the final
      examination, for a statistically significant difference in prevalence (P = .03).
      Visual acuity decreased two or more Snellen lines during the follow-up period in
      34 (71%) of 48 eyes, the prevalence of which was significantly higher in eyes
      with vitreomacular attachment at the final examination (28 of 34, 82%) than in
      eyes with vitreomacular separation at the final examination (six of 14, 43%) (P =
      .01). CONCLUSION: Even though vitreomacular separation may improve the prognosis
      of a macular hole, stage 2 lesions usually will develop an enlarged hole and
      decreased visual acuity.

PMID- 7733183
TI  - Dose-related difference in progression rates of cytomegalovirus retinopathy
      during foscarnet maintenance therapy. AIDS Clinical Trials Group Protocol 915
      Team.
AB  - PURPOSE: A previous dose-ranging study of foscarnet maintenance therapy for
      cytomegalovirus retinopathy showed a positive relationship between dose and
      survival but could not confirm a relationship between dose and time to first
      progression. This retrospective analysis of data from that study was undertaken
      to determine whether there was a relationship between dose and progression rates,
      which reflects the amount of retina destroyed when progression occurs. METHODS:
      Patients were randomly given one of two foscarnet maintenance therapy doses (90
      mg/kg of body weight/day [FOS-90 group] or 120 mg/kg of body weight/day [FOS-120
      group] after induction therapy. Using baseline and follow-up photographs and pre
      established definitions and methodology in a masked analysis, posterior
      progression rates and foveal proximity rates for individual lesions, selected by
      prospectively defined criteria, were calculated in each patient. Rates were
      compared between groups. RESULTS: The following median rates were greater for the
      FOS-90 group (N = 8) than for the FOS-120 group (N = 10): greatest maximum rate
      at which lesions enlarged in a posterior direction (43.5 vs 12.5 microns/day; P =
      .002); posterior progression rate for lesions closest to the fovea (42.8 vs 5.5
      microns/day; P = .010); and maximum foveal proximity rate for either eye (32.3 vs
      3.4 microns/day; P = .031). CONCLUSION: Patients receiving higher doses of
      foscarnet have slower rates of progression and therefore less retinal tissue
      damage during maintenance therapy. A foscarnet maintenance therapy dose of 120
      mg/kg of body weight/day instead of 90 mg/kg of body weight/day may help to
      preserve vision in patients with cytomegalovirus retinopathy.

PMID- 7733184
TI  - Viral sensitivity testing in patients with cytomegalovirus retinitis clinically
      resistant to foscarnet or ganciclovir.
AB  - PURPOSE: Resistance to antiviral therapy is a potential cause of progression of
      cytomegalovirus retinitis in patients with the acquired immunodeficiency
      syndrome. We investigated the results of viral sensitivity testing in a series of
      patients with clinically resistant retinitis who had positive results of blood or
      urine cytomegalovirus cultures. METHODS: All patients with newly diagnosed
      cytomegalovirus retinitis between January 1990 and December 1991 were
      prospectively studied. Blood and urine cultures for cytomegalovirus were obtained
      in a nonrandomized subgroup of this group. The results of in vitro sensitivity to
      foscarnet and ganciclovir, determined by a DNA hybridization assay, were then
      analyzed in seven patients with clinically resistant cytomegalovirus retinitis
      and whose blood or urine culture results, or both, were positive for
      cytomegalovirus while on a treatment regimen. RESULTS: Foscarnet-resistant
      cytomegalovirus (ID50 > 300 microM) was isolated from two patients, one of whom
      was being treated with foscarnet. Ganciclovir-resistant cytomegalovirus (ID 50 >
      6.0 microM) was isolated from four patients, three of whom were being treated
      with ganciclovir. Foscarnet- and ganciclovir-resistant cytomegalovirus occurred
      with previous ganciclovir therapy in one patient. Clinical improvement occurred
      in three patients whose change in therapy was based on viral sensitivity testing.
      In general, prolonged therapy with one drug was associated with a progressive
      increase in the ID 50 for that drug. CONCLUSIONS: Viral resistance to foscarnet
      or ganciclovir may explain refractory cytomegalovirus retinitis in some patients.

PMID- 7733185
TI  - Clinicopathologic study of retinal and choroidal biopsies in intraocular
      inflammation.
AB  - PURPOSE: We reviewed the clinical and histopathologic features of 33 intraocular
      tissue biopsy specimens from 32 patients and assessed the value of retinal and
      chorioretinal biopsies performed in patients with intraocular inflammation.
      METHODS: Twenty-four endoretinal biopsies and nine chorioretinal or choroidal
      biopsies were performed. On the basis of clinical indications, the specimens were
      processed for light microscopy, electron microscopy, immunohistochemical
      staining, in situ DNA hybridization, and polymerase chain reaction. RESULTS: Of
      the 24 endoretinal biopsy specimens, 19 were from patients with clinical signs
      suggestive of viral retinitis. Overall, the diagnosis of viral retinitis was
      suggested by electron microscopy, immunohistochemical staining, in situ DNA
      hybridization, or polymerase chain reaction in 53% (ten of 19) biopsies. The
      preoperative diagnosis was confirmed in seven of ten biopsies in cases of
      suspected cytomegalovirus retinitis, in one of seven biopsies in cases of
      suspected acute retinal necrosis, and in two of two biopsies in cases of
      progressive outer retinal necrosis. The remaining five endoretinal biopsies
      disclosed Candida in one specimen, subretinal fibrosis in one, and chronic
      inflammation in three. Histologic examination of the nine chorioretinal or
      choroidal biopsies disclosed lymphoma in two specimens, a subretinal neovascular
      membrane in one, uveal melanocytic proliferation in one, toxoplasmic
      retinochoroiditis in one, viral retinitis in one, and long-standing inflammation
      in three. CONCLUSION: In select cases of intraocular inflammation, intraocular
      tissue biopsies may provide clinically useful information.

PMID- 7733186
TI  - The effect of globe fixation on ablation zone centration in photorefractive
      keratectomy.
AB  - PURPOSE: For optimal vision, the ablation zone in photorefractive keratectomy
      should be centered over the entrance pupil. During ablation, the globe can be
      immobilized by the surgeon, with a suction ring around the corneoscleral limbus.
      Alternatively, the globe can be immobilized by patient fixation on a target,
      unassisted by the surgeon. We investigated which method results in better
      centration of the ablation zone over the entrance pupil, by using an objective,
      mathematical method to determine the ablation zone center. METHODS: Forty-eight
      eyes from 48 patients who underwent photorefractive keratectomy by the two
      techniques were studied retrospectively. The centers of the ablation zones were
      objectively determined by a weighted center of mass algorithm applied to the
      preoperative minus postoperative difference maps. The validity of the objective
      method was confirmed by comparison to subjective estimates of ablation zone
      centers made by independent human observers. RESULTS: The 19 eyes treated by
      surgeon fixation had an average decentration of the ablation zone of 0.63 +/-
      0.31 mm (range, 0.01 to 1.00 mm), and the 29 eyes treated by patient fixation had
      an average decentration of 0.41 +/- 0.23 mm (range, 0.11 to 1.18 mm) (P = .027).
      CONCLUSIONS: The center of the ablation zone can be determined mathematically
      from the topographic map, to avoid observer bias. In this study, unassisted
      patient fixation during photorefractive keratectomy produced more accurate
      centration of the ablation zone than did surgeon fixation and has the potential
      for maximizing the quality of vision postoperatively.

PMID- 7733187
TI  - Mottled cyan opacification of the posterior cornea in contact lens wearers.
AB  - PURPOSE: We studied patients who had mottled cyan-colored opacities of the cornea
      to better understand the cause and prognosis of this entity. METHODS: We reviewed
      examinations of patients who had a mottled cyan opacification of the cornea. Risk
      factors, including contact lens wear and exposure to heavy metals, were analyzed.
      Clinical findings, pachymetry specular microscopy, and progression of the
      abnormality were noted. RESULTS: Six patients who had a mottled cyan
      opacification at the level of Descemet's membrane were identified. These
      opacities were located in the peripheral and midperipheral cornea. All patients
      had bilateral findings, had visual acuities of 20/20 or better, and were
      asymptomatic. All patients had worn soft contact lenses bilaterally for periods
      ranging from seven to 14 years. CONCLUSION: All patients had the similar clinical
      appearance of a mottled cyan opacification at the level of Descemet's membrane in
      the peripheral cornea. Long-term contact lens wear appears to be associated;
      however, the exact cause is unclear.

PMID- 7733188
TI  - Scanning laser polarimetry to measure the nerve fiber layer of normal and
      glaucomatous eyes.
AB  - PURPOSE: To determine whether retardation (change in polarization) measurements
      of healthy subjects and glaucoma patients obtained by using a confocal scanning
      laser polarimeter correspond to known properties of the nerve fiber layer.
      METHODS: A polarimeter, an optical device used to measure the change in linear
      polarization of light (retardation), was interfaced with a scanning laser
      ophthalmoscope to obtain retardation data at 65,536 locations (256 x 256 pixels)
      in a study of normal subjects and patients with primary open-angle glaucoma. To
      validate the instrument, we compared our measurements with known properties of
      the human retinal nerve fiber layer in 105 normal subjects. Additionally, we
      compared retardation measurements in eyes of 64 normal subjects and 64 age
      matched glaucoma patients treated in a referral practice. RESULTS: In normal
      eyes, mean (+/- S.D.) peripapillary retardation was highest in the superior and
      inferior arcuate regions and lowest in the temporal and nasal regions, 12.0 +/-
      1.9, 13.1 +/- 2.0, 7.0 +/- 1.8, and 7.0 +/- 1.6 degrees, respectively.
      Retardation decreased toward the periphery and was lower over blood vessels. In
      normal eyes, retardation decreased with increasing age in the superior and
      inferior regions. Mean retardation was statistically significantly higher among
      normal eyes than glaucoma eyes in the inferior and superior regions but not in
      the temporal or nasal areas. CONCLUSIONS: Scanning laser polarimetry provides
      quantitative measurements that correspond to known properties of the retinal
      nerve fiber layer in normal and glaucomatous eyes.

PMID- 7733189
TI  - Influence of the time interval between instillation of two drops of
      cyclopentolate 1% on refraction and dilation of the pupil in children.
AB  - PURPOSE: Because the usual length of time to instill two drops of cyclopentolate
      1% (five to ten minutes) is time-consuming and inconvenient to clinical staff as
      well as to the child and the child's parents, we investigated the influence of
      the time interval between the instillation of the two drops on refraction and
      mydriasis in children. METHODS: We conducted a crossover study on 48 children at
      the Tel-Aviv Medical Center. Gender, iris color, ethnic origin, and age were
      recorded. Two cyclopentolate 1% eyedrops were instilled at a one- or five-minute
      time interval. Retinoscopy was performed and the mydriatic effect was recorded.
      One week later, the procedure was repeated, this time with a different time
      interval. RESULTS: The time interval between the instillation of the two drops
      had no significant influence on retinoscopy results (P = .65 and P = .50 for
      right and left eyes, respectively) or on pupil dilation (P = .377 and P = .113
      for right and left eyes, respectively). CONCLUSIONS: Instilling two drops of
      cyclopentolate 1% one minute apart is as effective as instilling them five
      minutes apart.

PMID- 7733190
TI  - Hypertension and lens opacities from the Beaver Dam Eye Study.
AB  - PURPOSE: To examine the relationship between hypertension and lens opacities, and
      the use of antihypertensive agents. METHODS: A total of 4,926 adults, 43 to 84
      years of age, living in Beaver Dam, Wisconsin, at the time of a private census,
      were invited to participate in a study that included a medical interview and an
      examination that included ocular photography. All study procedures and
      photographic grading were done according to standard protocols. RESULTS:
      According to analysis with the Liang-Zeger multiple logistic regression model,
      people with hypertension were more likely to have posterior subcapsular opacities
      than people without hypertension (odds ratio, 1.39; 95% confidence interval,
      1.05, 1.84). Specific medications for hypertension did not meaningfully affect
      the risk. Hypertension was associated with increased risk in both those with and
      without diabetes. CONCLUSIONS: Hypertension is associated with increased risk of
      posterior subcapsular opacities. The pathophysiologic mechanisms that may explain
      the relationship are unknown. Incidence data will give a better indication of
      temporal relationship between hypertension, medications to lower blood pressure,
      and lens opacities.

PMID- 7733191
TI  - Assessment of intraocular pressure by palpation.
AB  - PURPOSE/METHODS: Corneal specialists may assess the intraocular pressure by
      palpation although this technique has never been validated. We explored the
      reliability of a tactile assessment of the intraocular pressure in comparison to
      Goldmann tonometry. RESULTS/CONCLUSION: There was little correlation between
      tactile assessment of the intraocular pressure and tonometry. However, palpation
      was moderately successful in identifying most eyes (five of seven eyes) with an
      intraocular pressure greater than 30 mm Hg. Although palpation was generally
      inaccurate, it may serve as a warning for marked increases in intraocular
      pressure exceeding 30 mm Hg.

PMID- 7733192
TI  - Eyelid laceration sustained in an attack by a rabid desert fox.
AB  - PURPOSE/METHODS: Two patients were bitten on the face by a rabid desert fox and
      sustained eyelid lacerations. The patients were examined and they received the
      same prophylactic treatment: human rabies immunoglobulin, intramuscularly and at
      the laceration site, and rabies human-diploid cell vaccine. RESULTS/CONCLUSIONS:
      One patient survived; the other died. Eyelid laceration sustained by a bite of a
      rabid animal is a life-threatening condition; patients should receive prompt
      rabies prophylaxis.

PMID- 7733193
TI  - Incidence of adenoviral and chlamydial coinfection in acute follicular
      conjunctivitis.
AB  - PURPOSE/METHODS: After we studied a case of chlamydial and adenoviral coinfection
      in a 20-year-old woman, we determined the incidence of chlamydial infection in
      patients with acute adenoviral conjunctivitis. In a randomized retrospective
      study, we evaluated 100 specimens of patients with culture-proven adenoviral
      conjunctivitis. RESULTS/CONCLUSIONS: Three of 100 (3%) specimens tested positive
      for chlamydial DNA using polymerase chain reaction. Adenoviral and chlamydial
      coinfection is rare, yet should be considered in patients with prolonged
      follicular keratoconjunctivitis.

PMID- 7733194
TI  - Episcleral osteocartilaginous choristoma.
AB  - PURPOSE/METHOD: A 31-year-old woman had a hypertropia and an episcleral
      choristoma in the superotemporal quadrant of the globe. The choristoma was
      examined. RESULTS/CONCLUSIONS: Gross and histopathologic examination showed bone
      and cartilage components in the tumor, which refutes the previously accepted
      membranous growth pattern of episcleral osseous choristomas.

PMID- 7733195
TI  - Intranasal visualization for nasolacrimal duct intubation.
AB  - PURPOSE/METHODS: To improve intranasal visualization of nasolacrimal procedures
      we use a self-retaining nasal speculum with or without a sinuscope.
      RESULTS/CONCLUSIONS: Placement and retrieval of silicone stents can be
      accomplished with less trauma than with a blind sweep technique. Additionally,
      the valve of Hasner can be seen and the creation of false passages avoided.

PMID- 7733196
TI  - Ocular findings in a family with Sotos syndrome (cerebral gigantism).
AB  - PURPOSE/METHODS: We examined the ocular features in a two-generation family with
      Sotos syndrome (cerebral gigantism). Sotos syndrome is characterized by excessive
      growth in prenatal and early life, advanced bone age, and typical facial
      features. RESULTS/CONCLUSION: One patient had presenile nuclear sclerotic
      cataracts, megalophthalmos, hypoorbitism, and exotropia. One of her daughters had
      megalocornea, exophoria, and iris hypoplasia. Her other daughter had
      megalocornea. The ophthalmologist can play an important role in the diagnosis and
      treatment of Sotos syndrome.

PMID- 7733197
TI  - Clinical course and systemic correlates of retinopathy of prematurity in
      quintuplets.
AB  - PURPOSE/METHODS: We studied clinical correlates of retinopathy of prematurity in
      four surviving quintuplets with similar low birth weights and gestational age of
      27 weeks. Prospective serial ophthalmoscopic examinations and retrospective chart
      analysis were used. RESULTS/CONCLUSIONS: Retinopathy of prematurity varied among
      the neonates from stage 2 with total regression to threshold progressing to
      retinal detachment. Severity of eye disease correlated with duration of
      mechanical ventilation and of parenteral nutrition, as well as frequency of
      hypoglycemia and of hypercapnia. Poor outcome correlated inversely with weight
      gain.

PMID- 7733198
TI  - Recurrent acute multifocal placoid pigment epitheliopathy in two cousins.
AB  - PURPOSE/METHODS: To test the hypothesis that there may be inherited
      predisposition in acute multifocal placoid pigment epitheliopathy, HLA typing was
      undertaken in two cousins with recurrent disease. RESULTS/CONCLUSIONS: Both
      cousins were shown to have HLA antigens DR2 but not B7; both antigens have been
      associated with this disorder previously. This finding is compatible with the
      concept that DR2 may be associated with an increased risk of recurrent disease.

PMID- 7733199
TI  - Electrophysiologic abnormalities in two cases of familial amyloidosis.
AB  - PURPOSE/METHODS: We recorded electrophysiologic data of two patients with
      familial amyloidosis. RESULTS/CONCLUSIONS: Only minor abnormalities could be
      demonstrated clinically and by means of fluorescein angiography in one patient.
      Considerable alterations of electrophysiologic responses could be found in both
      patients. These results suggest that an early retinal or optic nerve involvement
      in amyloidosis could be detected by using these noninvasive techniques.

PMID- 7733200
TI  - Optic disk swelling and abducens palsies associated with OKT3.
AB  - PURPOSE/METHODS: Orthoclone OKT3 is a monoclonal murine IgG immunoglobulin used
      to treat acute cellular rejection of allografted organs. Aseptic meningitis and
      meningoencephalopathy are known adverse side effects from the drug. OKT3 caused
      additional ophthalmologic and neurologic complications in an 18-year-old woman
      who was treated for transplanted kidney graft rejection. Papilledema and
      bilateral abduction deficits developed. RESULTS/CONCLUSIONS: Results of magnetic
      resonance imaging and magnetic resonance angiography were unremarkable. Lumbar
      puncture disclosed increased intracranial pressure and sterile meningeal
      inflammation. Most of the symptoms resolved by one week after discontinuation of
      OKT3. Ophthalmologists and neurologists should be aware that optic disk swelling
      and abducens palsies can be associated with OKT3 when used in the treatment of
      transplanted kidney graft rejection.

PMID- 7733201
TI  - Reproducibility of retinal nerve fiber layer evaluation by dynamic scanning laser
      ophthalmoscopy.

PMID- 7733202
TI  - Critical period for restoration of normal stereoacuity in acute-onset comitant
      esotropia.

PMID- 7733203
TI  - Silicone intubation without intranasal fixation for treatment of congenital
      nasolacrimal duct obstruction.

PMID- 7733204
TI  - The Hull House era: vintage years for children.

PMID- 7733205
TI  - Paternal caregiving and incest: test of a biosocial model.
AB  - The existence of a biosocial mechanism for inhibiting incest through early
      caretaking contact was explored in a comparison between incestuous fathers and a
      nonincestuous control sample. Low involvement in caretaking was found to be a
      risk factor for incest, even after controlling for other predisposing conditions.
      However, it appeared that caretaking has its effect by enhancing more general
      parental feelings and capacities, rather than by inhibiting a father's sexual
      interest in the daughter, as proposed in the original biosocial theory.

PMID- 7733206
TI  - A social-ecological analysis of adolescent suicidal ideation.
AB  - The effects of family, school, peers, and religion on adolescent suicidal
      ideation were investigated using self-derogation as a mediating variable. As was
      hypothesized, the effects of different social variables were largely mediated by
      self-derogation. Family variables were found to be more salient predictors of
      both self-derogation and suicidal ideation than were nonfamily variables.

PMID- 7733207
TI  - Black/white interracial young adults: quest for a racial identity.
AB  - The racial self-identification of 119 young adults of mixed black and white
      racial heredity was explored. Data showed interracial identity to be the most
      prevalent, and that it was associated with the least conflict.
      Compartmentalization into a private interracial identity and a public black one
      appeared to be the most frequently utilized coping mechanism for dealing with
      societal pressures to negate white roots.

PMID- 7733208
TI  - Gender differences among homeless persons: special services for women.
AB  - Data from a survey of men and women in urban shelters for the homeless revealed
      that, while women were more likely than men to request a variety of services,
      most of the difference was accounted for by the subgroup of women accompanied by
      children. Homeless men and women without children exhibited few differences in
      the number of services they requested.

PMID- 7733209
TI  - Psychological impact of the Los Angeles riots on Korean-American victims:
      implications for treatment.
AB  - The psychological impact of the 1992 Los Angeles riots on 202 Korean-American
      victims who sustained financial loss or physical injury was investigated. Results
      indicate that the majority of these riot victims underwent severe distressed and
      experienced symptoms of post-traumatic stress disorder. Related research on
      trauma survivors is reviewed and implications for treatment are discussed.

PMID- 7733210
TI  - Emotional availability in infants' relationships with multiple caregivers.
AB  - Emotional availability was rated in infants' relationships with significant
      caregivers over a nine-month period. Infant responsivity to and involvement of
      caregivers was found to be related to individual sensitivity, while each
      relationship appeared to be unique, and not based on the nature of the infants'
      relationships with their mothers.

PMID- 7733211
TI  - Parent-child interactions in alcoholic and nonalcoholic families.
AB  - A community-recruited sample of alcoholic and nonalcoholic families was
      videotaped in a standardized play task involving parents and their preschool-aged
      sons. Microanalyses revealed that alcoholic families had lower dyadic synchrony,
      that parents were viewed as less able to engage their children, and that the
      coders liked the control parents and children more. Variations in the parent
      child interactions are discussed.

PMID- 7733212
TI  - Motherhood for women with serious mental illness: pregnancy, childbirth, and the
      postpartum period.
AB  - Although women with serious mental illness have normal fertility rates, the
      literature points to multiple risk factors and a paucity of emotional and
      economic support during the initial phases of parenthood. Since most research has
      focused on child outcomes, the extent and nature of parenting problems
      experienced by these mothers are not adequately understood. An emphasis on the
      context of parenting and the meaning of pregnancy and childbearing to these
      mothers is called for and implications for research and clinical practice are
      discussed.

PMID- 7733213
TI  - Adolescent parricide: an integration of social cognitive theory and clinical
      views of projective-introjective cycling.
AB  - Case histories of parricide by adolescents frequently reveal a history of abuse
      on the part of the victim and acute depression and suicidal ideation by the
      adolescent. This paper seeks to integrate an established concept of suicide as
      escape from "aversive self-awareness" through cognitive deconstruction with
      clinical observations of "projective-introjective cycling" of aggressive
      impulses, as a means of better understanding and preventing violence toward
      intimate others.

PMID- 7733214
TI  - Into the mouths of babes.

PMID- 7733215
TI  - Clinical interventions with latency-age children of high conflict and violence.
AB  - Children who live in divorced families where conflict is high are often witness
      to intermittent or frequent verbal or physical aggression between their parents.
      A theoretical framework and a group treatment model with case vignettes are
      presented for understanding and intervening with latency-age children of such
      parents.

PMID- 7733216
TI  - Meeting the needs of children in poverty.

PMID- 7733217
TI  - Differential diagnosis of ataque de nervios.
AB  - Characteristics of ataque de nervios, a culturally condoned expression of
      distress that is most frequently seen in Hispanic women, are described. It has
      symptoms in common with affective and anxiety disorders, with which it can co
      occur, and these are delineated for purposes of differential diagnosis. Possible
      reasons for the preponderance of the condition in women are discussed, along with
      suggested intervention strategies.

PMID- 7733218
TI  - Working with traumatic material: effects on Holocaust Memorial Museum staff.
AB  - Preparation for the opening of the United States Holocaust Memorial Museum in
      Washington, D.C., in April 1993, exposed workers to potentially disturbing
      personal artifacts of Holocaust victims and other reminders of the horrors of the
      Holocaust. The process of psychological consultation is described, and the
      resultant approaches to interventions designed to lower distress among museum
      workers and volunteers are discussed.

PMID- 7733219
TI  - Factors predicting use of mental health and social services by children 6-16
      years old: findings from the Ontario Child Health Study.
AB  - Correlates of mental health and social service utilization are examined based on
      Ontario Child Health Study data. Findings indicate that psychiatric disorder as a
      predictor of service use may be confounded by school performance and parental use
      of services, thus calling into question the extent to which program planning
      should be based on prevalence rates of child psychiatric disorder. Children from
      low-income families tend to make greater use of available services, suggesting
      that programs need to be tailored more specifically to their needs.

PMID- 7733220
TI  - Preventing school failure, drug use, and delinquency among low-income children:
      long-term intervention in elementary schools.
AB  - A six-year, school-based prevention program, which modified classroom teacher
      practices, offered parent training, and provided child social skills training,
      was evaluated for its effects on school failure, drug abuse, and delinquency
      among low-income urban children. Compared to a low-income control group, children
      in the intervention group showed enhanced school commitment and class
      participation. The girls in the group also evidenced lower rates of substance use
      initiation, while the boys exhibited increased social and school work skills.

PMID- 7733221
TI  - Electrophysiology of adult cat cardiac ventricular myocytes: changes during
      primary culture.
AB  - To investigate the nature of electrophysiological changes in adult cat cardiac
      ventricular myocytes that may occur when cells are maintained in primary culture
      for 1-2 wk, the electrophysiology of cells freshly isolated from collagenase
      perfused hearts (day 0 controls) was compared with that of cells maintained in
      primary culture for up to 14 days 1) on a two-dimensional (2D) surface (laminin
      coated coverslips), which allowed for changes in cellular morphology, or 2) in a
      three-dimensional (3D) alginate matrix, which minimized changes in cell shape.
      Action potentials and whole cell ionic currents were recorded using a
      conventional whole cell patch technique. Whereas cellular resting potential and
      the depth of the "notch" terminating phase 1 were diminished relative to controls
      in 2D- and 3D-cultured cells, the action potential duration and the incidence of
      early afterdepolarizations (EADs) were increased relative to controls in 2D- but
      not in 3D-cultured cells. Corresponding alterations in whole cell ionic currents
      included a 40% reduction in inwardly rectifying K current (IK1) conductance (GK1)
      and a 90% reduction in transient outward K current (Ito) conductance (Gto) in 2D-
      and 3D-cultured cells relative to day 0 controls and a 50% increase in L-type Ca
      current (ICa-L) conductance (GCa-L) in 2D-cultured cells relative to 3D-cultured
      cells and day 0 controls. The reduction in Gto in long-term culture was half
      maximal by days 7 and 8 and could not be attributed to reduced Ito availability,
      involvement of a noninactivating Ito, the cell culture procedure itself, or the
      presence of serum in the culture media. Gto was larger in day 0 cells from a
      heart with right ventricular hypertrophy than in day 0 normal control cells and
      was reduced subsequent to placement of cells in 3D culture for 19 days. The
      results suggest that long-term culture and change in cellular morphology can
      affect the electrophysiology of cardiac ventricular myocytes.

PMID- 7733222
TI  - Urea activation of K-Cl transport in human erythrocytes.
AB  - This report prompted us to examine the effect of urea on K-Cl cotransport in
      human erythrocytes. In human erythrocytes, urea activated K-Cl cotransport
      reversibly and in a concentration-dependent manner. Pretreatment with okadaic
      acid abolished the urea activation of transport, suggesting that exposure to urea
      resulted in net dephosphorylation of the transporter or a key regulator and that
      the action of urea was exerted proximal to the phosphorylation-dephosphorylation
      step. At a concentration of 200 mM, urea activated K-Cl cotransport without any
      delay, even in the absence of cell swelling. However, with increasing urea
      concentrations, an appreciable increase in lag time was observed before the final
      steady-state flux was reached, suggesting that urea inhibits a regulatory kinase.
      The latter conclusion was also supported by the finding that, at any given urea
      concentration, the lag time for activation was greater than the lag time for
      deactivation. Mg depletion activated cotransport, and urea had no additional
      stimulatory effect in Mg-depleted cells. In urea-pretreated cells, swelling
      further activated cotransport, but without any measurable delay, in contrast to a
      time lag of 8 min when control cells (not exposed to urea) were swollen. The
      latter finding suggests that urea promotes the conversion of transporters from
      the resting to the partially activated state. These findings raise the
      possibility that high concentrations of urea in the renal medulla may play a role
      in the decrease in cell volume that occurs during the maturation of reticulocytes
      and young erythrocytes, both in normal subjects and in subjects with
      hemoglobinopathies.

PMID- 7733223
TI  - Effects of urea on K-Cl cotransport in sheep red blood cells: evidence for two
      signals of swelling.
AB  - The activation proceeds with a delay, like activation by swelling. Swelling of
      cells in urea activates K uptake further, but with no delay. Inactivation after
      removal of urea also proceeds without delay. With cotransport partially activated
      by reducing intracellular Mg concentration ([Mg]i) or with staurosporine, urea
      did not activate cotransport further. However, swelling activated cotransport
      further in these two types of cells. In terms of the three-state process for
      swelling-activation of K-Cl cotransport (P. B. Dunham, J. Klimczak, and P. J.
      Logue, J. Gen. Physiol. 101: 733-765, 1993), these results indicate that urea
      activates the first conversion, A-->B, and does so by inhibiting the reverse
      reaction promoted by a kinase, just as reducing [Mg]i does. Stimulation of
      cotransport by urea is nearly completely reversed by shrinkage, whereas
      activation by reducing [Mg]i is reversed only approximately 35%. Therefore urea
      inhibits the kinase indirectly, like swelling, by reducing macromolecular
      crowding of cytoplasmic proteins (A. P. Minton, G. C. Coleclasure, and J. C.
      Parker. Proc. Natl. Acad. Sci. USA 89: 10504-10506, 1992). Since swelling
      activates cotransport in two ways, one mimicked by urea and one not, there must
      be two signals of swelling, one a reduction of macromolecular crowding and the
      other probably a mechanical signal.

PMID- 7733224
TI  - Isoform-specific induction of the low-density lipoprotein receptor gene by
      platelet-derived growth factor.
AB  - We investigated the effect of recombinant platelet-derived growth factor (PDGF)
      isomers on low-density lipoprotein (LDL) receptor gene expression and compared
      this with two indexes of cell growth response: expression of the immediate early
      gene c-myc and the rate of DNA synthesis. In human skin fibroblasts and NIH 3T3
      cells, the PDGF-BB homodimer was more effective in inducing the LDL receptor gene
      and cell growth response compared with the PDGF-AA homodimer. The second
      messenger pathways utilized by PDGF receptors for enhancing LDL receptor gene
      response could, however, be dissociated from those utilized for enhancing c-myc
      gene response and were insensitive to inhibitors of tyrosine phosphorylation.
      Inhibition of tyrosine kinase activity inhibited c-myc gene response to PDGF-BB
      at 10(-8) M but had little effect on LDL receptor gene response. Such inhibition
      increased expression of the LDL receptor gene in the presence of the PDGF-AA
      isomer. Our results indicate that the response of the LDL receptor gene to PDGF
      isoforms reflects cellular growth response. However, different transduction
      pathways are utilized for PDGF activation of the c-myc and LDL receptor genes in
      mesenchymal cells.

PMID- 7733225
TI  - Regulation of mouse beta 3-adrenergic receptor gene expression and mRNA splice
      variants in adipocytes.
AB  - This study examined the regulation of murine beta 3-receptor mRNA and determined
      whether the recently described mRNA splice variants are differentially regulated
      by agents that alter total beta 3-receptor mRNA levels. In vivo treatment of mice
      with the beta 3-receptor agonist BRL-26830 reduced total beta 3-transcripts by
      64% in white adipose tissue but did not alter the mRNA splicing pattern. Further
      analysis in cultured 3T3-F442A adipocytes showed that isoproterenol,
      dexamethasone, or phorbol 12-myristate 13-acetate also greatly reduced beta 3
      receptor mRNA levels without selectively altering poly-U-containing transcripts.
      Blockade of transcription with actinomycin D produced a rapid loss of beta 3
      receptor mRNA, which was prevented by blockade of mRNA translation with
      cycloheximide. However, neither actinomycin D nor cycloheximide altered the
      splicing pattern of beta 3-receptor mRNA. Analysis of transcription rate by
      nuclear run-off assay indicated that 8-bromoadenosine 3',5'-cyclic monophosphate
      and phorbol 12-myristate 13-acetate reduce beta 3-receptor gene transcription and
      that suppression of transcription is sufficient to account for the reduction in
      beta 3-receptor mRNA levels by these agents.

PMID- 7733226
TI  - MRF4, Myf-5, and myogenin mRNAs in the adaptive responses of mature rat muscle.
AB  - We studied the possible role of specific muscle regulatory factors (MRF) in the
      adaptive response to changes in contractile activity in mature skeletal muscle.
      The tibialis anterior muscle of anesthetized female rats was subjected to low
      frequency stimulation, static stretch, or a combination of both. Message levels
      of MRF were observed after 2 h of activity, and the subsequent 20-h recovery
      period by slot blot and in situ hybridizations for MRF4, Myf-5, and myogenin. A
      combination of stimulation and stretch for 2 h increased MRF4 (11.6 +/- 5.3-fold)
      and Myf-5 (6.6 +/- 1.4-fold). In situ hybridization showed abundance in some
      regions of the muscle with positive staining near peripheral nuclei of both large
      and small fibers. Message levels remained high for 30 min and declined to near
      control levels by 20 h of recovery. Myogenin mRNA levels were unaffected by any
      manipulations. Neither stretch alone nor 10 Hz of electrical stimulation alone
      induced a significant increase in MRF. We conclude that myonuclei, and possibly
      activated myoblasts, increase expression of Myf-5 and MRF4 after a combination of
      both stimulation and stretch for 2 h.

PMID- 7733227
TI  - Improved culture conditions stimulate gluconeogenesis in primary cultures of
      renal proximal tubule cells.
AB  - Unlike renal proximal tubule cells (RPTC) in vivo, RPTC cultured in standard
      conditions are hypoxic, glycolytic, and not gluconeogenic. This study
      investigated the effects of glucose and lactate on glycolysis and gluconeogenesis
      in rabbit RPTC cultured in conditions of increased oxygen supply (Shake).
      Confluent Shake cultures grown in the presence of glucose exhibited increased
      oxygen consumption and decreased glycolysis compared with stationary (Still)
      cultures. Addition of 5 mM lactate to a 5 mM glucose medium decreased net glucose
      consumption and glucose oxidation in Shake cultures by 34 and 50%, respectively,
      and resulted in net lactate consumption. Addition of 5 mM lactate to a glucose
      free medium resulted in a threefold increase in net glucose production (0.024 +/-
      0.003 vs. 0.074 +/- 0.013 mumol.mg protein-1.day-1) in Shake cultures. Net
      glucose production further increased to 0.430 +/- 0.020 and 1.640 +/- 0.040
      mumol.mg protein-1.day-1 when glucose reuptake was inhibited by 1 mM phloridzin
      or 1 mM phloridzin + 1 mM phloretin, respectively. These results show that, under
      conditions of improved oxygenation and in the presence of lactate and
      physiological levels of glucose and insulin, RPTC aerobic metabolism increases
      and glucose metabolism changes from glycolysis and net lactate production to
      gluconeogenesis and net lactate consumption.

PMID- 7733228
TI  - Urokinase receptor mediates mechanical force transfer across the cell surface.
AB  - The tripartite complex formed by the urokinase receptor, urokinase, and its
      inhibitor is an enzymatic system that controls plasmin formation involved in
      degradation of extracellular matrix proteins. With the use of magnetic twisting
      cytometry with urokinase-coated ferromagnetic beads, we applied mechanical stress
      directly to the urokinase receptor on the surface of human myogenic cells in
      culture. The stiffness and the stiffening response measured through the urokinase
      receptor resembled those of integrins, which are linked mechanically to the
      cytoskeleton. Furthermore, stiffness decreased with disruption of actin
      microfilaments. These results demonstrate that the urokinase receptor is coupled
      mechanically to the cytoskeleton. Inhibition of the tripartite complex formation
      with antibodies led to a twofold increase in cytoskeletal stiffness. A stiffened
      cytoskeleton might impede cytoskeletal remodeling and reorganization and thus
      impede cell motility. Our results demonstrate that the urokinase receptor
      mediates mechanical force transfer across the cell surface. As such, it is a
      novel pathway to regulate cytoskeletal stiffness and, thereby, possibly to
      modulate motility of normal and abnormal adherent cells.

PMID- 7733229
TI  - Na-K-Cl cotransport regulates intracellular volume and monolayer permeability of
      trabecular meshwork cells.
AB  - The trabecular meshwork (TM) of the eye plays a critical role in modulating
      intraocular pressure (IOP) through regulation of aqueous humor outflow, although
      the underlying mechanisms remain unknown. Ethacrynic acid, an agent known to
      inhibit Na-K-Cl cotransport of a number of cell types, recently has been reported
      to increase aqueous outflow and lower IOP through an unknown effect on the TM. In
      vascular endothelial cells and a variety of other cell types, the Na-K-Cl
      cotransporter functions to regulate intracellular volume. The present study was
      conducted to evaluate TM cells for the presence of Na-K-Cl cotransport activity
      and to test the hypothesis that modulation of cotransport activity alters
      intracellular volume and, consequently, permeability of the TM. We demonstrate
      here that bovine and human TM cells exhibit robust Na-K-Cl cotransport activity
      that is inhibited by bumetanide and by ethacrynic acid. Our studies also show
      that TM cell Na-K-Cl cotransport is modulated by a variety of hormones and
      neurotransmitters. Inhibition of the cotransporter either by bumetanide,
      ethacrynic acid, or inhibitory hormones reduces TM intracellular volume, whereas
      stimulatory hormones increase cell volume. In addition, shrinkage of the cells by
      hypertonic media stimulates cotransport activity and initiates a subsequent
      regulatory volume increase. Permeability of TM cell monolayers, assessed as
      transmonolayer flux of [14C]sucrose, is increased by hypertonicity-induced cell
      shrinkage and by bumetanide. These findings suggest that Na-K-Cl cotransport of
      TM cells is of central importance to regulation of intracellular volume and TM
      permeability. Defects of Na-K-Cl cotransport may underlie the pathophysiology of
      glaucoma.

PMID- 7733230
TI  - Physiological roles and properties of potassium channels in arterial smooth
      muscle.
AB  - This review examines the properties and roles of the four types of K+ channels
      that have been identified in the cell membrane of arterial smooth muscle cells.
      1) Voltage-dependent K+ (KV) channels increase their activity with membrane
      depolarization and are important regulators of smooth muscle membrane potential
      in response to depolarizing stimuli. 2) Ca(2+)-activated K+ (KCa) channels
      respond to changes in intracellular Ca2+ to regulate membrane potential and play
      an important role in the control of myogenic tone in small arteries. 3) Inward
      rectifier K+ (KIR) channels regulate membrane potential in smooth muscle cells
      from several types of resistance arteries and may be responsible for external
      K(+)-induced dilations. 4) ATP-sensitive K+ (KATP) channels respond to changes in
      cellular metabolism and are targets of a variety of vasodilating stimuli. The
      main conclusions of this review are: 1) regulation of arterial smooth muscle
      membrane potential through activation or inhibition of K+ channel activity
      provides an important mechanism to dilate or constrict arteries; 2) KV, KCa, KIR,
      and KATP channels serve unique functions in the regulation of arterial smooth
      muscle membrane potential; and 3) K+ channels integrate a variety of vasoactive
      signals to dilate or constrict arteries through regulation of the membrane
      potential in arterial smooth muscle.

PMID- 7733231
TI  - Increase in [Ca2+]i by CCh in adult rat sympathetic neurons are not dependent on
      intracellular Ca2+ pools.
AB  - We have examined the effects of the muscarinic agonists, carbachol (CCh) and
      oxotremorine (Oxo), on the intracellular free Ca2+ concentration ([Ca2+]i) in
      acutely dissociated sympathetic neurons from adult rats using fura 2-based
      microfluorometry. The drugs increased [Ca2+]i by 86 +/- 7 and 38 +/- 10 nM for
      CCh and Oxo, respectively (both 10 microM). Basal [Ca2+]i was 52 +/- 3 nM.
      Depletion of the caffeine-sensitive Ca2+ store or blockade of the Ca(2+)
      adenosinetriphosphatase with thapsigargin did not alter the effect of either
      agonist on the rise in [Ca2+]i. On the other hand, the omission of Ca2+ from the
      perfusion solution or the use of TA-3090, a Ca2+ channel antagonist, blocked the
      effects of CCh and Oxo. In whole cell current-clamp recordings, the muscarinic
      agonists elicited a depolarization and action potential firing, which probably
      explained the rise in [Ca2+]i observed with microfluorimetric recording. In
      addition to their direct effects on the [Ca2+]i, muscarinic agonists also reduced
      the rise in [Ca2+]i induced by a nicotinic agonist. This inhibitory effect,
      observed in 68% of cells that responded to the nicotinic agonist, was blocked by
      atropine and pertussis toxin, whereas the muscarinic agonist-induced increase in
      [Ca2+]i was blocked by atropine but was pertussis toxin insensitive. These
      results suggest that at least two muscarinic receptors are present on sympathetic
      neurons and that they mediate opposite effect on the fluctuation of [Ca2+]i.

PMID- 7733232
TI  - Adenosine attenuates calcium paradox injury: role of adenosine A1 receptor.
AB  - The present study was conducted to test the hypothesis that adenosine attenuates
      the Ca2+ paradox (PD) injury via stimulation of adenosine A1 receptors linked to
      Gi proteins in the isolated rat heart. Treatment of adenosine reduced maximum
      lactate dehydrogenase release and ATP loss compared with regular Ca2+ PD.
      Recovery of mechanical activity after Ca2+ repletion was observed only in heart
      treated with adenosine before and during the Ca2+ PD. Significant preservation of
      myocytes was observed in adenosine-treated hearts compared with the regular Ca2+
      PD. Adenosine exerted its effects in a dose-dependent manner, being maximum at
      100 microM. The protective effects were mediated by adenosine A1 receptor
      activation since the adenosine A1 receptor agonist N6-phenylisopropyladenosine
      provided protection similar to adenosine-treated heart and was blocked by A1
      receptor antagonist and pertussis toxin. This study suggests that protection by
      adenosine against the lethal injury of the Ca2+ PD is mediated by adenosine A1
      receptor and a pertussis toxin-sensitive inhibiting G protein.

PMID- 7733233
TI  - UVB radiation-activated genes induced by transcriptional and posttranscriptional
      mechanisms in rat keratinocytes.
AB  - The mechanisms utilized by ultraviolet B (UVB) radiation in the regulation of
      gene expression, as well as the genetic targets for transmission of the UVB
      signal, remain incompletely understood. To elucidate the mechanisms and targets
      for UVB activation in mammalian cells, we screened a keratinocyte cDNA library
      with differentially subtracted UVB-enriched cDNA probes. Twenty-three UVB-induced
      cDNA clones were isolated, including cDNAs for keratin, elongation factor-1
      alpha, ferritin heavy chain, thioltransferase, cyclin G, cornifin, cellubrevin,
      poly(A) binding protein, and the surfeit locus. The temporal kinetics of maximal
      RNA induction following UVB exposure were heterogeneous, varying from 1 to 24 h
      post-UVB radiation. Analysis of the regulation of gene expression demonstrated
      that the levels of most UVB-induced mRNAs were also independently induced by
      serum and cycloheximide, features previously described for genes induced by DNA
      damage and members of the immediate early gene family. In contrast to results
      from studies of immediate early genes, treatment of keratinocytes with both serum
      and cycloheximide resulted in superinduction of only one mRNA transcript. Nuclear
      run-on assays demonstrated that UVB radiation increased the transcription rate in
      8 of 23 genes, suggesting that UVB radiation utilizes both transcriptional and
      posttranscriptional mechanisms for the modulation of keratinocyte gene
      expression. The identification of a group of UVB-inducible keratinocyte genes
      should prove useful for the characterization of the genomic response to UVB
      radiation and the analysis of the molecular mechanisms underlying the UVB
      regulation of gene expression.

PMID- 7733234
TI  - c-myb affects intracellular calcium handling in vascular smooth muscle cells.
AB  - The protooncogene c-myb is responsible for elevating intracellular calcium
      concentration ([Ca2+]i) at the G1/S interface in vascular smooth muscle cells
      (VSMC). However, the molecular components of this pathway are undefined, and the
      biological effects of increased levels of divalent cation are unknown. We have
      demonstrated that growth-arrested c-myb-transfected VSMC, compared with wild type
      VSMC, exhibit a fourfold increased number of insulin-like growth factor I (IGF-I)
      receptors, increased amount of secreted IGF-I activity, and a twofold increased
      level of [Ca2+]. The c-myb transfected cells, compared with wild type cells, also
      possess a twofold increased rate of calcium influx and a twofold decreased rate
      of calcium efflux. The elevated calcium influx rate of transfected cells is
      decreased to that of wild type cells with IGF-I neutralizing antibody, whereas
      the decreased calcium efflux rate of transfected cells is increased to that of
      wild type cells with antisense c-myb oligonucleotides. Proliferating wild type
      VSMC exhibit an increased calcium influx rate in late G1, which is dependent on
      production of augmented amounts of IGF-I activity but not increased levels of IGF
      I receptors. The wild type VSMC also show a decreased calcium efflux rate at the
      same point in the cell cycle, which is dependent on expression of c-myb. The
      treatment of wild type cells with antisense c-myb or IGF-I receptor
      oligonucleotides induces a late G1 block in cell proliferation, which can be
      overcome by exposure to the calcium ionophore, 4-bromo-A-27318, in amounts
      sufficient to raise [Ca2+]i to levels observed at the G1/S interface. We conclude
      that IGF-I/IGF-I receptors and c-myb are involved in control of [Ca2+]i at the
      G1/S interface by separately regulating the rates of calcium influx and efflux
      and that elevated levels of divalent cation are necessary for progression of VSMC
      into the S phase of the cell cycle.

PMID- 7733235
TI  - Energy-rich phosphates in slow and fast human skeletal muscle.
AB  - We investigated the relationship between energy-rich phosphate content and muscle
      fiber-type composition in human skeletal muscle using a combination of 31P
      nuclear magnetic resonance spectroscopy (NMR), histochemical, and biochemical
      analyses of muscle biopsies. Localized 31P spectra were collected simultaneously
      from the predominantly slow-twitch soleus muscle and the mixed (fast-twitch and
      slow-twitch) medial and lateral gastrocnemius muscles, using B1-insensitive
      Hadamard Spectroscopic Imaging. Biopsy samples were taken from the soleus and
      lateral gastrocnemius muscles before NMR investigation and analyzed for fiber
      type composition and succinic dehydrogenase (SDH) activity. Fiber-type
      composition was determined based both on myofibrillar actomyosin ATPase activity
      combined with cross-sectional area and on myosin heavy-chain composition.
      Localized spectroscopy demonstrated a significantly (P < 0.001) higher
      P(i)/phosphocreatine ratio in the soleus muscle (0.15 +/- 0.01) compared with the
      medial (0.12 +/- 0.01) and lateral (0.10 +/- 0.0) gastrocnemius. However, in
      vitro analysis of muscle biopsies showed only a moderate relationship between the
      basal phosphate content and myofibrillar actomyosin ATPase-based fiber-type
      composition and SDH activity, respectively.

PMID- 7733236
TI  - Muscarinic suppression of ATP-sensitive K+ channel in rabbit esophageal smooth
      muscle.
AB  - Smooth muscle cells from the rabbit esophageal muscularis mucosae were studied
      for the presence of ATP-sensitive K+ channel (KATP) and its inhibition by
      carbachol. Lemakalim (10 microM), a synthetic K+ channel opener, increased whole
      cell currents by -174 +/- 15 pA with 0.1 mM intracellular ATP concentration
      ([ATP]i) and -70 +/- 11 pA with 5 mM [ATP]i. Glibenclamide (10 microM) completely
      abolished the lemakalim-induced currents. These currents were therefore denoted
      as KATP. Carbachol (10 microM) suppressed KATP by 74 +/- 4% with 10 mM
      intracellular ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic
      acid (EGTA) concentration and 100% when EGTA was omitted from the pipette
      solution. Carbachol suppression was attenuated to 23 +/- 16% by the M3 receptor
      antagonist, p-flurohexahydrosiladifenidol (0.1 microM). KATP was also suppressed
      by phorbol 12-myristate 13-acetate (PMA; 100 nM) by 63 +/- 9%. The effects of
      both PMA and carbachol were significantly reduced by inhibitors of protein kinase
      C and tyrosine kinase. These results suggest that carbachol suppression of KATP
      is via M3 receptor subtype and the signaling pathway involves Ca2+, protein
      kinase C, and tyrosine kinase.

PMID- 7733237
TI  - Cation transport in mouse erythrocytes: role of K(+)-Cl- cotransport in
      regulatory volume decrease.
AB  - We investigated cation transport and cell volume regulation in erythrocytes of
      CD1 and C57/B6 mice. Swelling of cells from either strain stimulated K+ efflux
      that was insensitive to ouabain, bumetanide, and clotrimazole. Seventy-five
      percent of swelling-induced K+ efflux was Cl- dependent (inhibited by sulfamate
      or methanesulfonate, partially by NO3-, but not by SCN-) and was inhibited by
      okadaic acid (OA; 50% inhibitory concentration = 18 +/- 6 nM in CD1 and 10 +/- 4
      nM in C57/B6). In both strains, K+ efflux into isotonic medium was stimulated by
      staurosporine or by N-ethylmaleimide, and the latter was partially blocked by
      pretreatment of cells with OA. When cells of either strain were incubated in
      hypotonic medium or preswollen isosmotically with nystatin, OA-sensitive
      regulatory volume decrease (RVD) and K+ loss were observed. RVD produced by
      hypotonic swelling was prevented by Cl- replacement with sulfamate or
      methanesulfonate. These properties suggest the presence in outbred and inbred
      mouse erythrocytes of RVD mediated by K(+)-Cl- cotransport.

PMID- 7733238
TI  - Calponin is not phosphorylated during contractions of porcine carotid arteries.
AB  - Calponin and caldesmon were purified from porcine carotid arteries that were
      preincubated with [32P]orthophosphate, and the stoichiometry of phosphorylation
      was measured. In resting arteries, caldesmon was phosphorylated to a level of
      0.41 mol PO4/mol protein, while calponin was phosphorylated to levels < 0.01 mol
      PO4/mol protein. Stimulation by histamine (1 or 5 min), KCl (1, 5 or 60 min), or
      phorbol 12,13-dibutyrate (PDBu; 1 microM for 15 or 60 min) did not lead to
      measurable increases in the PO4 content of calponin. Because dephosphorylation of
      calponin during the purification procedure could account for these results, we
      also determined stoichiometries after firat denaturing endogenous phosphatases
      with trichloroacetic acid. In these experiments, calponin was determined to be
      phosphorylated to the same low levels as in the first set of experiments.
      Collectively, these data show that calponin is not phosphorylated to significant
      levels during contractions of carotid arteries under conditions where caldesmon
      phosphorylation is apparent. The circumstances under which calponin may be
      phosphorylated in intact smooth muscle, and the purpose that may be served by
      this potential regulatory process, remain to be determined.

PMID- 7733239
TI  - Norepinephrine and ANG II stimulate secretion of TGF-beta by neonatal rat cardiac
      fibroblasts in vitro.
AB  - Transforming growth factor-beta (TGF-beta) is a ubiquitous growth-regulating
      protein that is capable of influencing the growth and function of heart cells in
      vitro. To better understand the role TGF-beta might play as a paracrine mediator
      of cardiac hypertrophy, the expression, secretion, and growth effects of TGF-beta
      were examined. Neonatal cardiac fibroblasts in vitro secreted latent TGF-beta 1
      and TGF-beta 2 as high as 15 ng/10(6) cells. Angiotensin II (ANG II) and
      norepinephrine (NE) each augmented up to threefold the expression and secretion
      of latent TGF-beta 1 and TGF-beta 2 and also induced a shift in isoform
      predominance from beta 1 to beta 2. Each agent individually produced hypertrophic
      growth of neonatal cardiocytes and hyperplastic growth of cardiac fibroblasts.
      Paradoxically, the combination of NE and ANG II at intermediate and high
      concentrations resulted in less TGF-beta secretion (compared with either agent
      alone) and in hypertrophic growth of fibroblasts. These results suggest that the
      growth-promoting effects of ANG II and NE may in part be mediated via a paracrine
      stimulation of TGF-beta secretion.

PMID- 7733240
TI  - Signaling and growth responses of LLC-PK1/Cl4 cells transfected with the rabbit
      AT1 ANG II receptor.
AB  - Angiotensin II (ANG II) receptors of the AT1 subtype are present on the apical
      and basolateral membranes of renal proximal tubule cells. Cells of the proximal
      tubulelike cell line, LLC-PK1/Cl4, were transfected with an expression plasmid
      containing cDNA encoding the rabbit AT1 ANG II receptor. In transfected cells,
      specific binding of 125I-ANG II was detected on both apical and basolateral
      membranes; wild-type LLC-PK1/Cl4 cells did not express ANG II receptors. In
      transfected cells, apical or basolateral ANG II increased both S6 kinase activity
      and incorporation of [3H]leucine. In cells pretreated with pertussis toxin, the
      stimulatory effect of apical or basolateral ANG II on [3H]leucine incorporation
      was abolished. In contrast, ANG II did not affect mitogenesis, determined by
      [3H]thymidine incorporation. Apical or basolateral ANG II (10(-6) M) stimulated
      phosphoinositide turnover by 13.4 +/- 4.4% (n = 8) and 16.3 +/- 4.2% (n = 9),
      respectively. The activity of protein kinase C, determined by phosphorylation of
      a specific protein kinase C peptide substrate, was also stimulated by ANG II in
      transfected cells. Apical or basolateral ANG II had no significant effect on
      cellular adenosine 3',5'-cyclic monophosphate levels. In permeabilized
      transfected cells, apical ANG II (10(-6) M) inhibited the phosphorylation of a
      specific peptide substrate of protein kinase A; lower apical concentrations or
      basolateral ANG II were without significant effect. These results indicate that
      AT1 ANG II receptors sort to both apical and basolateral membranes in renal
      epithelial cells and are coupled to activation of phospholipase C. ANG II
      stimulates protein synthesis by binding to either apical or basolateral
      receptors; this effect requires coupling to G proteins and may be mediated by
      activation of S6 kinase. Because high concentrations of ANG II exist in proximal
      tubule, binding to apical and basolateral receptors may regulate proximal tubule
      cell growth under physiological conditions.

PMID- 7733241
TI  - Nerve growth factor stimulates rapid metabolic responses in PC12 cells.
AB  - Research into the effects of nerve growth factor (NGF) has involved study of
      either the signal transduction process or the morphological result of growth
      factor treatment (cell proliferation and/or differentiation). The Cytosensor
      Microphysiometer, a silicon-based biosensor system that allows the continuous and
      real-time monitoring of extracellular acidification rate changes of cells, was
      used to study the response of PC12 cells to NGF. Stimulation resulted in a rapid
      increase in the acidification rate of cells in a concentration-dependent fashion
      (0.1-200 ng/ml NGF; mean effective concentration value of 153 +/- 54 pM).
      Inhibition of the NGF receptor-linked protein tyrosine kinase by either genistein
      or K252a attenuated the acidification rate response to NGF. In addition, the
      acidification response to NGF could be modified by inhibiting Na+/H+ exchange
      and, separately, glycolysis. This implicates these processes in the metabolic
      response of PC12 cells to NGF stimulation.

PMID- 7733242
TI  - Adaptive differentiation of avian exocrine cells alters their pHi response to
      mAChR activation.
AB  - Muscarinic receptor-mediated changes in intracellular pH (pHi) were measured in
      isolated 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein-loaded cells,
      suspended in bicarbonate-containing media, from the exocrine nasal gland of
      freshwater-fed ducklings (Anas platyrhynchos). The pHi recovery from an acid load
      was sensitive to amiloride, required sodium ions in the external medium, and was
      independent of added bicarbonate. These findings are consistent with the
      hypothesis that the pHi recovery was mediated by a Na+/H+ exchanger. Muscarinic
      activation of cells resulted in a sustained cytosolic alkalinization that was
      sensitive to atropine and that was blocked by amiloride. Activation of protein
      kinase C (PKC) or inhibition of protein phosphatases mimicked the effect of
      receptor activation on pHi, whereas inhibitors of PKC blocked the response,
      indicating that phosphorylation of a major pHi control mechanism results in a
      shift of pHi to more alkaline values. In contrast, fully differentiated salt
      gland cells isolated from nasal glands of salt-stressed ducklings responded to
      muscarinic receptor activation with a transient cytosolic acidification. These
      findings raise the question whether the cytosolic alkalinization in muscarinic
      acetylcholine receptor-activated naive cells may serve as a signal or a
      permissive factor for the initiation of adaptive growth and/or differentiation
      processes observed in the salt glands of salt-stressed birds.

PMID- 7733243
TI  - Circulating hyaluronan levels in the rodent: effects of age and diet.
AB  - Circulating hyaluronan (HA) levels were investigated as a function of age and
      diet in Fischer 344 male rats. A biphasic pattern of age-related changes was
      observed in rats fed ad libitum a diet in which the protein source was soya/fish
      meal. HA levels in 3- to 6- and 22- to 29-mo-old rats were not statistically
      different. However, HA levels in 12- to 20-mo-old rats were 10-29% of the levels
      in younger or aged adults. HA levels were also measured in rats fed ad libitum a
      semisynthetic diet in which the protein source was hydrolyzed casein. Whereas the
      two colonies exhibited similar biphasic age-related changes, HA levels differed 4
      to 20-fold at every age examined. Caloric restriction affected HA levels in 19
      mo-old casein-fed rats; HA levels were 2.3 times higher than age-matched controls
      and were not statistically different from young or aged animals. Serum and plasma
      HA levels were identical in the same individuals at all ages tested. These data
      suggest that HA turnover and metabolism in the rat are affected by age, dietary
      composition, and caloric intake.

PMID- 7733244
TI  - Duality of plasmin effect on cytosolic free calcium in human platelets.
AB  - Plasmin caused a modest and gradual increase in platelet cytosolic Ca2+, mediated
      through both Ca2+ mobilization and external Ca2+ entry. This response was
      associated with accelerated Ca2+ extrusion and protein tyrosine phosphorylation.
      Plasmin-enhanced external Ca2+ entry and Ca2+ extrusion (but not Ca2+
      mobilization) were attenuated by the tyrosine kinase inhibitor, genistein.
      Plasmin inhibited the thrombin-evoked increase in cytosolic Ca2+ and also
      inhibited the Ca2+ response to the tethered peptide TRAP-6 of the thrombin
      receptor. Furthermore, plasmin inhibited the binding of 125I-labeled alpha
      thrombin to platelets. The inhibitory effect of plasmin on the thrombin response
      shared some characteristics with the effect of protein kinase C stimulators but
      was not reversed by protein kinase C inhibitors. Plasmin did not change platelet
      cyclic nucleotides. These results suggest a dual effect of plasmin. Plasmin
      produces a small rise in platelet cytosolic Ca2+ and a tyrosine kinase-dependent
      enhancement of Ca2+ turnover (external Ca2+ influx and Ca2+ efflux). However, it
      also attenuates the thrombin-evoked cytosolic Ca2+ response by blocking Ca2+
      mobilization and slowing the rate of external Ca2+ influx. The latter feature
      would result in a plasmin-induced inhibition of thrombogenesis.

PMID- 7733245
TI  - Heart gap junction preparations reveal hemiplaques by atomic force microscopy.
AB  - Current structural models of gap junctions indicate two apposed plasma membranes
      with hexagonally packed hemichannels in each membrane aligning end to end. These
      channels connect the cytoplasms of contacting cells. Images of isolated rat heart
      gap junctions have been made with the atomic force microscope in aqueous media.
      We show that native cardiac gap junctions have a thickness of 25 +/- 0.6 nm. This
      decreases to 17 nm when they are treated with trypsin, which is known to remove
      some cytoplasmic components of connexin 43. Imaging shows subunits with a center
      to center spacing of approximately 9-10 nm and long range hexagonal packing,
      measurements in agreement with studies using freeze-fracture and negative-stain
      electron microscopy. In addition to gap junctions, we imaged structures that had
      all the characteristics of native gap junctions except their thickness was
      limited to 9-11 nm. They also show long range hexagonal packing and center to
      center spacing of 9-10 nm. These structures decrease in thickness, to 6-9 nm,
      when treated with trypsin. We have called these structures hemiplaques. They
      appear to be present endogenously in the preparation, as we have ruled out their
      being an artifact of imaging by AFM. However, it remains to be determined if they
      are a consequence of the procedure used in isolating gap junctions or a possible
      intermediary in gap junction formation.

PMID- 7733246
TI  - C-type natriuretic peptide neuromodulates via "clearance" receptors.
AB  - A recently discovered endogenous autacoid, C-type natriuretic peptide, was tested
      in a pheochromocytoma (PC12) cell line for effects on 1) catecholamine release
      induced by a depolarizing stimulus, 2) guanylyl and adenylyl cyclase activities,
      and 3) specific 125I-labeled atrial natriuretic peptide (ANP) binding. C-type
      natriuretic peptide suppressed evoked neurotransmitter release in the absence of
      guanylyl cyclase activation or adenylyl cyclase inhibition; however, both a
      "clearance" (ANP-C) receptor binding agent, des-[Gln18Ser19Gly20Leu21Gly22]-ANF
      (4-23)-NH2 (cANF), and pertussis toxin prevented this neuromodulatory effect. The
      C-type natriuretic peptide preferentially bound to receptors that also bound
      cANF. The results suggest that C-type natriuretic peptide suppressed evoked
      neurotransmitter efflux by binding to ANP-C receptors coupled to a pertussis
      toxin-sensitive process; furthermore, the neuromodulatory effect of C-type
      natriuretic peptide occurred independently of guanylyl cyclase activation or
      adenylyl cyclase inhibition. The novel aspects of these findings are 1)
      neuromodulatory effects of C-type natriuretic peptide, 2) guanylyl cyclase
      independent actions of C-type natriuretic peptide, and 3) ANP-C receptors
      mediating C-type natriuretic peptide actions.

PMID- 7733247
TI  - Voltage-gated calcium currents have two opposing effects on the secretion of
      aldosterone.
AB  - Using Ca2+ channel blockers with different specificities for L- and T-type Ca2+
      channels, we have investigated the roles of these two channel types in K(+)
      induced aldosterone secretion. In whole cell voltage-clamp experiments, the
      spider toxin omega-agatoxin-IIIA (omega-Aga-IIIA) completely blocks L-type Ca2+
      channels but has no effect on T-type Ca2+ channels. In contrast, Ni2+ and 1,4
      dihydropyridines block both L- and T-type Ca2+ channels. Secretion induced by 7
      mM extracellular K+ concentration ([K+]o) is unaffected by omega-Aga-IIIA but is
      strongly inhibited by Ni2+ or the 1,4-dihydropyridine, nitrendipine. This
      suggests that physiological increases in [K+]o stimulate aldosterone secretion
      primarily by enhancing Ca2+ entry through T-type Ca2+ channels. Surprisingly,
      secretion induced by 60 mM [K+]o is enhanced by omega-Aga-IIIA or Ni2+ and is
      inhibited by the L-type Ca2+ channel activator BAY K 8644. Nitrendipine (1 nM)
      also stimulates such secretion, although higher concentrations are inhibitory
      (concentration inhibiting 50% of maximal response approximately 30 nM). If
      extracellular Ca2+ concentration is reduced from 1.25 to 0.5 mM, secretion
      induced by 60 mM [K+]o is enhanced, and Ni2+ or low nitrendipine become
      inhibitory. Together, these results that L-type Ca2+ currents can reduce
      steroidogenesis and that the role of these currents was previously misconstrued
      because 1,4-dihydropyridines modify secretion by multiple mechanisms. Thus Ca2+
      entry can function as a negative modulator of steroid secretion.

PMID- 7733248
TI  - Alteration of the sodium current in cat cardiac ventricular myocytes during
      primary culture.
AB  - To determine the response of cardiac Na current (INa) in adult cardiac
      ventricular myocytes to culture, single isolated ventricular myocytes from
      collagenase-perfused adult cat hearts were placed in primary culture for up to 2
      wk on a two-dimensional (2D) surface (laminin-coated coverslips), which allowed
      the morphology of the myocytes to change markedly, or in a three-dimensional
      matrix (3D) of alginate, in which cell shape changed only minimally. Action
      potentials and INa were recorded from groups of 1) freshly isolated myocytes
      serving as the control (day 0),2) cells maintained in 2D culture for 9-14 days
      (2D, day 9-14), and 3) cells cultured in alginate for 9-14 days (3D, day 9-14)
      with use of a conventional whole cell patch technique. Maximal upstroke velocity
      (Vmax) of the action potential was reduced by approximately 50% in 2D- and 3D
      cultured cells relative to controls. INa in 2D- and 3D-cultured cells was
      strikingly different from that in control myocytes. Half-maximal voltage (V 1/2)
      for the chord conductance-voltage relationship was shifted approximately 15 mV
      negatively to that for controls in 2D- and 3D-cultured cells. INa steady-state
      availability curve also shifted negatively relative to controls in 2D- and 3D
      cultured myocytes, but the magnitude of this shift (approximately 16-20 mV) was
      greater than that for the chord conductance-voltage curve.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7733249
TI  - Functional role of intrahypothalamic release of oxytocin and vasopressin:
      consequences and controversies.
AB  - This brief review of vasopressin (VP) and oxytocin (OT) release into the
      extracellular space of the supraoptic (SON) and paraventricular (PVN) nuclei
      focuses on recent data illustrating the significance of their intranuclear
      release and the potential functional consequences. With the use of in vitro
      techniques, it has been demonstrated that administration of exogenous OT causes
      local peptide release and that, in vivo, this facilitates the milk ejection
      reflex. These findings lead to the idea that endogenous peptides are released
      into the hypothalamic nuclei. Microperfusion techniques have been used to monitor
      the dynamics of intranuclear OT and VP release in response to distinct stimuli.
      It is clear that intranuclear release of OT plays a role during reproductive
      states (parturition and lactation) and that intranuclear release of VP and OT is
      involved in osmoregulation. This review discusses 1) the origin of the
      intranuclearly released peptides, 2) stimuli which cause release into the
      hypothalamic nuclei, and 3) the function of intranuclear VP and OT, e.g.,
      regulation of local morphology, feedback mechanisms and synchronization, and the
      possible role in regulating autonomic function and behavior.

PMID- 7733250
TI  - Dietary fat and adiposity: a dose-response relationship in adult male rats fed
      isocalorically.
AB  - This study examined the effects of increasing levels of dietary fat fed
      isocalorically on body weight, body composition, and adipose distribution. Adult
      male rats were weight matched into four groups. One group that was fed a low-fat
      diet (12%) served as reference controls. The other three groups were fed diets of
      24, 36, or 48% fat in amounts to equal the energy intake of the control group.
      After 6 wk, body weights of the four groups were not significantly different.
      Intrascapular brown fat did not differ between groups. Total body fat and adipose
      depot weights, however, increased in proportion to the level of fat in the diet.
      Total body fat and retroperitoneal and mesenteric depot weights of the 48% fat
      group were greater than controls (P < 0.05). Mesenteric fat in this group was
      also significantly increased over all other groups (P < 0.05). These results show
      that high-fat diets fed to adult animals cause increased body fat in the absence
      of significant changes in body weight and that mesenteric fat is increased
      disproportionately.

PMID- 7733251
TI  - Synergism between IL-1 beta and TNF-alpha on the activity of the pituitary
      adrenal axis and on food intake of rats.
AB  - We investigated the effects of separate and combined intraperitoneal
      administration for 3 days of recombinant human interleukin-1 beta (IL-1) and
      recombinant human tumor necrosis factor-alpha (TNF) on plasma adrenocorticotropic
      hormone (ACTH) and corticosterone (B) levels, adrenal weight, food intake, and
      rectal temperature. Rats were equipped with a jugular cannula for daily blood
      sampling and with an intraperitoneally implanted Alzet osmotic minipump loaded
      with either saline, IL-1 (2.0 micrograms/day), TNF (0.2, 2.0, or 10.0
      micrograms/day), or IL-1 in combination with TNF. Plasma ACTH and B levels and
      adrenal weight were significantly increased, in a dose-dependent way, by
      simultaneous infusion of IL-1 and TNF but not by administration of either
      cytokine alone. Chronic administration of IL-1 alone induced a significant
      decrease in food intake and a significant elevation of rectal temperature,
      whereas infusion of only the highest dose of TNF significantly elevated rectal
      temperature. Coinfusion of IL-1 and TNF induced both effects in a dose-dependent
      and synergistic way. Our data show that simultaneous infusion of IL-1 and TNF in
      rats has a synergistic effect on the activity of the pituitary-adrenal axis as
      well as on food intake and rectal temperature. The existence of two pathways,
      which act synergistically, may increase the sensitivity of the host to respond to
      subtle inflammatory stimuli.

PMID- 7733252
TI  - Mechanisms of action of somatostatin on human TSH-secreting adenoma cells.
AB  - The mechanisms of somatostatin (SRIH) action on thyroid-stimulating hormone (TSH)
      secretion were examined using human TSH-secreting adenoma cells. SRIH (10(-7) M)
      inhibited TSH secretion through a pertussis toxin-sensitive G protein. SRIH also
      inhibited forskolin- and 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP)
      induced TSH secretion. The mechanisms of this inhibition were investigated by
      measuring intracellular Ca2+ concentration ([Ca2+]i) and by electrophysiological
      experiments. Application of 10(-7) M SRIH reduced the [Ca2+]i, whereas forskolin
      and 8-BrcAMP increased the [Ca2+]i. Simultaneous application of SRIH abolished
      the forskolin-and the 8-BrcAMP-induced [Ca2+]i increase, indicating that the SRIH
      induced decrease in [Ca2+]i was independent of the reduction in intracellular
      cAMP. Under current clamp using the whole cell clamp, 10(-7) M SRIH
      hyperpolarized the membrane and arrested Ca(2+)-dependent action potentials,
      which accounted for the SRIH-induced decrease in [Ca2+]i. Voltage clamp
      experiments revealed that this membrane hyperpolarization resulted from the
      activation of an inward-rectifying K+ current through a pertussis toxin-sensitive
      G protein. Intracellular injection of cAMP (100 microM) through the patch pipette
      did not abolish the SRIH-induced K+ current, indicating that the activation of
      SRIH-induced K+ channels was independent of intracellular cAMP. From these data,
      we concluded that SRIH-induced membrane hyperpolarization was responsible for the
      [Ca2+]i decrease, which in turn inhibited TSH secretion. Application of
      thyrotropin-releasing hormone (TRH; 10(-7) M) caused an increase in the [Ca2+]i,
      composed of an initial transient increase followed by a sustained increase. SRIH
      inhibited the sustained increase in [Ca2+]i. SRIH also inhibited the TRH-induced
      decrease in the membrane conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733253
TI  - Ascorbate concentration in osteoblastic cells is elevated by transforming growth
      factor-beta.
AB  - Transforming growth factor-beta modulates the proliferation, differentiation, and
      synthetic activity of osteoblasts, but its mechanisms of action are not fully
      understood. Because ascorbate also influences osteoblast differentiation and is a
      cofactor for collagen synthesis, the present study examined the effect of
      transforming growth factor-beta on the initial rate of transport and steady-state
      concentration of ascorbate in an osteoblastic cell line. UMR-106 rat osteosarcoma
      cells accumulated reduced vitamin C from culture medium. Virtually all
      accumulation of ascorbate was accomplished by a saturable Na(+)-dependent
      transport mechanism. Transforming growth factor-beta increased the initial rate
      of ascorbate transport, measured in either attached or suspended cells. Within 24
      h, the growth factor also increased the steady-state intracellular concentration
      of ascorbate, without significantly changing cell volume or the DNA or protein
      content of cultures. These data provide evidence that Na(+)-ascorbate cotransport
      activity controls ascorbate concentration in osteoblasts. Furthermore, the
      results indicate that both the transport rate and steady-state concentration of
      ascorbate in these cells are regulated by transforming growth factor-beta.

PMID- 7733254
TI  - Sulfation pathway of thyroid hormone metabolism in selenium-deficient male rats.
AB  - Male Sprague-Dawley rats were fed a selenium-deficient yeast-based laboratory
      diet or a control diet for 6 wk. The tissue type I 5'-monodeiodinase (5'-MDI)
      activity and the immunoassayable 5'-MDI were significantly (P < 0.05) reduced in
      the liver and the kidney but not in the thyroid of selenium-deficient rats. The
      mean serum concentrations of thyroxine sulfate (T4S), 3,3',5'-triiodothyronine
      sulfate (T3S), and reverse T3 sulfate (rT3S) (ng/dl) were significantly increased
      in selenium-deficient rats (15.7, 59.4, and 22.8, respectively, n = 12) compared
      with control rats (< 1.0, 18.5, and 9.1, respectively, n = 12, P < 0.01). Kinetic
      studies were carried out during a constant infusion of unlabeled sulfated
      iodothyronines (T4S, T3S, or rT3S, n = 5-6/group) at a rate of 1 microgram/h by
      Alzet minipump for 48 h. The data showed that elevated serum concentrations of
      T4S or T3S in the selenium-deficient rat are due both to reduced metabolic
      clearance rate (MCR, mean, l.kg-1.day-1, 7.4 for T4S and 4.5 for T3S in selenium
      deficiency vs. 12 and 9.2, respectively in controls, P < 0.05) and increased
      production rate (mean, microgram.kg-1.day-1, 1.2 for T4S, and 2.7 for T3S in
      selenium deficiency vs. 0.12 and 1.7, respectively, in the controls, P < 0.05).
      However, the increased serum rT3S concentration in selenium-deficient rats is due
      mainly to reduced MCR (mean, l.kg-1.day-1, 34 vs. 67 in controls, P < 0.05) and
      its daily production rate remained unchanged in selenium deficiency (mean,
      microgram.kg-1.day-1, 7.6 vs. 6.1 in the control group, P > 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7733255
TI  - SAM prevents impairment of glucose-stimulated insulin secretion caused by hexose
      deprivation or starvation.
AB  - Succinic acid monomethyl ester (SAM) was recently proposed as an insulinotropic
      tool in non-insulin-dependent diabetes mellitus. Three models were now used to
      investigate whether SAM protects the B-cell against the impairment of glucose
      stimulated insulin release caused by either glucose deprivation or starvation. In
      the first model, preincubation of the islets for 180 min at low glucose
      concentration in the presence of SAM prevented the decrease in the secretory
      response to D-glucose otherwise observed during a subsequent incubation. In the
      second model, an impaired secretory response to D-glucose was observed after 3
      day culture at low (2.8 or 5.6 mM) as distinct from high (11.1 mM) hexose
      concentration and the presence of SAM in the culture medium again protected
      against this anomaly. In the third model, the infusion of SAM for 3 days to
      starved rats restored the secretory potential of isolated islets to a level
      comparable to that otherwise found in fed rats. Thus, during glucose deprivation
      or starvation, SAM is indeed able to maintain B-cell responsiveness to D-glucose.

PMID- 7733256
TI  - Impaired postprandial clearance of triacylglycerol-rich lipoproteins in adipose
      tissue in obese subjects.
AB  - Adipose tissue is an important site of clearance of circulating triacylglycerol
      (TAG), especially in the postprandial period. Postprandial lipemia is usually
      increased in obesity. We studied the extraction of TAG from plasma and TAG-rich
      lipoproteins (TRLs) in subcutaneous adipose tissue in 11 control and 8 obese
      subjects before and after a mixed meal. Clearance of plasma TAG and very low
      density lipoprotein (VLDL)-TAG was decreased in the obese subjects after an
      overnight fast. After the meal, chylomicron-TAG extraction increased in the
      control group whereas VLDL-TAG clearance decreased; these changes were not seen
      in the obese group, in whom the VLDL particles appeared to be better able to
      compete with the chylomicrons for clearance by lipoprotein lipase. In the control
      subjects, removal of TAG from the TRL in the postprandial period was accompanied
      by a shift toward addition of cholesterol to the high-density lipoprotein (HDL)
      fraction; this was not observed in the obese subjects. We conclude that disturbed
      TRL-TAG clearance in adipose tissue is related both to the elevated plasma TAG
      concentrations and the depressed HDL-cholesterol concentrations typical of
      obesity.

PMID- 7733257
TI  - Effects of the normal nocturnal rise in cortisol on carbohydrate and fat
      metabolism in IDDM.
AB  - Plasma cortisol concentrations increase approximately three- to five-fold during
      sleep in healthy humans. To determine the effects of the normal nocturnal rise in
      cortisol on carbohydrate and fat metabolism independent of changes in endogenous
      insulin secretion, we studied the disposition of a mixed meal in individuals with
      insulin-dependent diabetes mellitus (IDDM) in whom the normal nocturnal rise in
      cortisol had been either prevented or mimicked by using metyrapone and a constant
      or variable hydrocortisone infusion. Insulin was infused intravenously on both
      occasions in amounts sufficient to create relative postprandial insulin
      deficiency. The nocturnal rise in cortisol resulted in an approximately 30 mg/dl
      greater (P < 0.001) peak postprandial glycemic excursion due to greater (P <
      0.01) systemic glucose appearance and inappropriately low (P < 0.05) tissue
      glucose uptake. The latter was most evident when postprandial glucose
      concentrations in the presence and absence of the nocturnal rise in cortisol were
      matched by means of an exogenous glucose infusion to avoid the confounding
      effects of differences in glycemia. The nocturnal rise in cortisol also resulted
      in increased (P < 0.01) incorporation of 14CO2 into glucose (an index of
      gluconeogenesis), decreased (P < 0.05) carbohydrate oxidation, and increased (P <
      0.05) rates of palmitate appearance, lipid oxidation, and beta-hydroxybutyrate
      concentrations. Thus the normal nocturnal rise in cortisol, independent of
      changes in insulin secretion, is an important regulator of postabsorptive and
      postprandial carbohydrate, fat, and ketone body metabolism in humans.

PMID- 7733258
TI  - Early alteration of insulin stimulation of PI 3-kinase in muscle and adipocyte
      from gold thioglucose obese mice.
AB  - The activation of phosphatidylinositol 3-kinase (PIK) was studied in vivo and in
      vitro in soleus muscle and adipocytes from young (8 wk) and old (30 wk) gold
      thioglucose obese mice. Insulin resistance assessed from muscle glucose transport
      and glycogen synthesis was present both in young and old obese mice. Adipocyte
      lipid synthesis and muscle glycolysis or glucose oxidation are not defective in
      young obese mice but become resistant later on. After incubation with 50 nM
      insulin, muscle antiphosphotyrosine-immunoprecipitable PIK activity was
      stimulated 5- to 10-fold in both young and old animals. This response was
      impaired by 56 and 75% in muscles from young and old obese mice, respectively.
      Insulin stimulation of receptor tyrosine kinase activity was only slightly
      decreased in muscle of young obese mice, whereas insulin receptor substrate 1
      (IRS-1) tyrosine phosphorylation was blunted. The altered PIK stimulation in
      muscle, which is present both in vivo and in vitro, is thus characterized by a
      reduced association of PIK activity with IRS-1 and appears to result from a
      diminished IRS-1 tyrosine phosphorylation. In adipocytes isolated from lean mice,
      antiphosphotyrosine-immunoprecipitable PIK increased 25-fold within 10 min of
      incubation with insulin. This stimulation was markedly altered both in young and
      old obese mice, whereas lipogenesis was insulin resistant only in old obese
      animals. In adipocytes from young obese mice, insulin's stimulatory effect on the
      phosphorylation of insulin receptor beta-subunit, pp60, and an exogenous
      substrate was normal, whereas IRS-1 tyrosine phosphorylation was markedly
      depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733259
TI  - Insulin induces translocation of GLUT-4 glucose transporters in human skeletal
      muscle.
AB  - Understanding the molecular mechanisms involved in the regulation of glucose
      transport into human muscle is necessary to unravel possible defects in glucose
      uptake associated with insulin resistance in humans. Here we report a strategy to
      subfractionate human skeletal muscle biopsies (0.5 g) removed from vastus
      lateralis during a euglycemic insulinemic clamp procedure. A sucrose gradient
      separated total membranes into five fractions. Fraction 25 (25% sucrose)
      contained the plasma membrane markers alpha 1- and alpha 2-subunits of the Na(+)
      K(+)-adenosinetriphosphatase and the GLUT-5 hexose transporter, recently
      immunolocalized to the cell surface of human skeletal muscle. The dihydropyridine
      receptor, a transverse tubule marker, was present exclusively in this fraction.
      The GLUT-4 glucose transporter was more concentrated in fraction 27.5 (27.5%
      sucrose) and largely diminished in plasma membrane markers. Open skeletal muscle
      biopsies were removed before and 30 min after clamping insulin to 550 pM. This
      increased GLUT-4 protein by 1.61-fold in fraction 25 and lowered it by 50% in
      fraction 27.5. Thus physiological concentrations of insulin induce translocation
      of glucose transporters from an internal membrane pool to surface membranes in
      human skeletal muscle.

PMID- 7733260
TI  - Biological activity of adrenocorticotropic hormone precursors on ovine adrenal
      cells.
AB  - Adrenocorticotropic hormone (ACTH) is synthesized in the corticotrophs as a
      precursor, pro-opiomelanocortin (POMC), which is processed via proACTH to ACTH.
      Both precursors and ACTH are secreted. Although the steroidogenic activity of
      ACTH is well characterized, that of the precursors is not. This study assessed
      the capacity of POMC and proACTH to alter cortisol synthesis. POMC and proACTH
      were prepared by subjecting medium, conditioned by exposure to DMS-79 cells, to
      Sephadex chromatography, and the bioactivity was assessed in cultured-dissociated
      ovine adrenal cells. Alone neither POMC (< or = 2.6 nM) nor proACTH (< or = 0.7
      nM) showed any consistent acute (6 h) stimulatory or inhibitory action on
      cortisol in either fetal or adult cells. In contrast, in fetal cells the
      precursors inhibited steroidogenic response to ACTH-(1-24). POMC at 2.6 nM, but
      not lower concentrations, decreased the cortisol responses to 0.01, 0.1, and 1 nM
      ACTH by at least 50%. ProACTH (0.70 and 0.23 nM) decreased the responses to ACTH
      at 0.01 nM by 89 and 67%, respectively, and at 0.1 nM by 49 and 34%,
      respectively. At 1 nM ACTH only 0.7 nM proACTH decreased the response to ACTH (by
      69%). In contrast, in adult adrenal cells, the precursors did not significantly
      reduce the response to ACTH (range 0.01-1 nM). Therefore, these data indicate
      that POMC and proACTH can inhibit the cortisol response to ACTH in fetal adrenal
      cells, an effect that is concentration dependent. The data suggest that
      precursors may play a physiological role, possibly regulating fetal plasma
      cortisol concentrations.

PMID- 7733261
TI  - Effects of lactate on glucose metabolism in healthy subjects and in severely
      injured hyperglycemic patients.
AB  - Hepatic glucose production is autoregulated during infusion of gluconeogenic
      precursors. In hyperglycemic patients with multiple trauma, hepatic glucose
      production and gluconeogenesis are increased, suggesting that autoregulation of
      hepatic glucose production may be defective. To better understand the mechanisms
      of autoregulation and its possible alterations in metabolic stress, lactate was
      coinfused with glucose in healthy volunteers and in hyperglycemic patients with
      multiple trauma or critical illness. In healthy volunteers, infusion of glucose
      alone nearly abolished endogenous glucose production. Lactate increased
      gluconeogenesis (as indicated by a decrease in net carbohydrate oxidation with no
      change in total [13C]carbohydrate oxidation) but did not increase endogenous
      glucose production. In patients with metabolic stress, endogenous glucose
      production was not suppressed by exogenous glucose, but lactate did not further
      increase hepatic glucose production. It is concluded that 1) in healthy humans,
      autoregulation of hepatic glucose production during infusion of lactate is still
      present when glycogenolysis is suppressed by exogenous glucose and 2)
      autoregulation of hepatic glucose production is not abolished in hyperglycemic
      patients with metabolic stress.

PMID- 7733262
TI  - Glucose homeostasis during exercise in humans with a liver or kidney transplant.
AB  - To investigate the role of liver nerve activity on hepatic glucose production
      during exercise, liver-transplant subjects (LTX, n = 7, 25-62 yr, 4-18 mo
      postoperative) cycled for 40 min, 20 min at 52 +/- 3% (SE) maximal O2 consumption
      (VO2max) and 20 min at 83 +/- 1% VO2max, respectively. Kidney-transplant (KTX)
      and healthy control subjects (C) matched for sex and age exercised at the same
      %VO2max as LTX. VO2max was lower in both LTX (1.59 +/- 0.12 l/min) and KTX (1.59
      +/- 0.07) than in C (2.60 +/- 0.26). At rest plasma renin and insulin were higher
      and plasma adrenocorticotropic hormone and cortisol lower in transplant
      corticosteroid-treated subjects compared with C. In LTX, hepatic glucose
      production (Ra) increased from 11.9 +/- 0.9 (rest) to 17.6 +/- 1.8 and 25.5 +/-
      1.8 mumol.min-1.kg-1 at 52 and 82% VO2max, respectively. Peripheral glucose
      uptake was similar to Ra, and glucose remained at basal postabsorptive levels.
      During exercise the Ra increase as well as norepinephrine, insulin, and growth
      hormone responses were similar in LTX compared with both KTX and C. The increase
      in epinephrine was smaller in LTX than in C, the only group showing an increase
      in cortisol. The increase in plasma renin activity during exercise was attenuated
      in KTX compared with LTX and C. During exercise blood lactate rose more and
      plasma glycerol and free fatty acid levels were lower in LTX and KTX compared
      with C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733263
TI  - Effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide
      I-(7-36) on insulin secretion.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide
      (GLP)-I-(7-36) are probably the most important "incretins," but there is
      controversy as to their relative insulinotropic activities. The effects of
      natural (np) and synthetic porcine (sp) GIP, synthetic human (sh) GIP, and GLP-I
      (7-36) on insulin secretion from the perfused rat pancreas were compared using
      gradient perfusion. Insulin secretion was increased by both spGIP and GLP-I-(7
      36) at concentrations of approximately 16 pM. Maximal responses to GLP-I-(7-36)
      in the presence of 16.7 mM glucose were slightly greater than with npGIP or
      spGIP, but with 10 mM glucose spGIP and GLP-I-(7-36) exerted equivalent effects.
      Responses to shGIP were greatly reduced compared with spGIP. In the presence of
      50 pM spGIP or GLP-I-(7-36) the glucose threshold was 4.5 +/- 0.11 mM. The data
      indicate that GLP-I-(7-36) and porcine GIP are equally insulinotropic and share
      the same glucose threshold for activity, whereas shGIP is less active. At the
      concentrations found postprandially, however, GIP is likely to be the more
      important incretin.

PMID- 7733264
TI  - Stable isotope determination of plasma lactate conversion into glucose in fasting
      infants.
AB  - To quantify lactate gluconeogenesis, we developed a gas chromatography-mass
      spectrometry method based on the infusion of [6,6-2H2]glucose and [3-13C]lactate
      tracers to 12 infants aged 1-25 mo fasting for 11.5 +/- 1.5 h. Both rates of
      appearance of plasma glucose (26.7 +/- 2.6 mumol.kg-1.min-1, 4.8 +/- 0.5 mg.kg
      1.min-1) and lactate (30.8 +/- 3.1 mumol.kg-1.min-1, 2.8 +/- 0.3 mg.kg-1.min-1)
      were remarkably elevated compared with adult values. The interconversion of
      plasma lactate and glucose was determined by 1) measuring the incorporation of
      13C from [3-13C]lactate into plasma glucose; 2) correcting for the metabolic
      exchange of carbon atoms in the tricarboxylic acid cycle. For this purpose, an
      additional group of six infants was infused with [3-13C]lactate, and the
      distribution of 13C at specific carbon positions in the glucose molecule was
      determined using relevant ions in the electron-impact mass spectrum of its
      1,2,5,6-diisopropylidene-3-O-acetyl-alpha-furanosyl derivative; and 3) measuring
      the reverse conversion of glucose to lactate in five other infants infused with
      [1-13C]glucose. We found that 54 +/- 2% of glucose was derived from plasma
      lactate (14.4 +/- 1.3 mumol.kg-1.min-1, 2.6 +/- 0.2 mg.kg-1.min-1). Lactate and
      glucose rates of appearance were correlated (r = 0.58, P < 0.05) and decreased
      with fasting duration (r = 0.66, P < 0.02). The correction factor for carbon
      exchange in the tricarboxylic acid cycle was 1.14 +/- 0.11.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7733265
TI  - Metabolism of (R,S)-1,3-butanediol acetoacetate esters, potential parenteral and
      enteral nutrients in conscious pigs.
AB  - The (R,S)-1,3-butanediol-acetoacetate monoesters and diester are nonionized
      sodium-free precursors of ketone bodies (beta-hydroxybutyrate and acetoacetate).
      They represent a convenient form of ketone body administration for parenteral and
      enteral nutrition. We have studied the metabolism of the esters in the conscious
      pig, an animal in which ketogenesis is congenitally impaired. Some pigs were
      infused for 3 h, intravenously or intragastrically, with the esters or with (R,S)
      1,3-butanediol at 30% of the hourly caloric requirement. Other pigs were given
      intragastric boluses of esters or of (R,S)-1,3-butanediol at 15% of the daily
      caloric requirement. Our data show that continuous infusion of the esters at 30%
      of the caloric requirement leads to low concentrations of (R,S)-1,3-butanediol
      (0.1 mM) and total ketone bodies (0.5 mM). In pigs given intragastric boluses of
      esters at 15% of the daily caloric requirement, concentrations of (R,S)-1,3
      butanediol and total ketone bodies peaked briefly at 2-3 and 5 mM, respectively.
      No deleterious side effects were observed in any group, including no hypoglycemia
      and no acidosis. Thus the (R,S)-1,3-butanediol acetoacetate esters appears to be
      well utilized as a nutrient by the pig despite its impaired ketogenesis.

PMID- 7733266
TI  - Long-term adaptive responses to dietary protein restriction in chronic renal
      failure.
AB  - Six patients with chronic renal failure (glomerular filtration rate 18 +/- 2
      ml/min) underwent two 10-day admissions separated by at least 1 yr of outpatient
      therapy with a very low-protein diet (VLPD) providing 0.28 g protein.kg-1.day-1
      plus an amino acid-ketoacid supplement. During each Clinical Research Center
      admission, subjects completed a 5-day nitrogen balance (BN), and whole body
      protein turnover was measured during fasting and feeding using intravenous [1
      13C]leucine and intragastric [5,5,5-2H3]leucine. Outpatient dietary protein
      compliance was very good (25 vs. 20 g protein/day or 125% goal), whereas energy
      intake was only 69% of goal (24 vs. 35 kcal.kg-1.day-1). During the 16 +/- 2 mo
      of dietary therapy, there were no changes in serum proteins or anthropometrics.
      BN after > or = 1 yr of dietary therapy was neutral and did not differ from
      initial values (+0.46 +/- 0.20 vs. +0.55 +/- 0.19 g N/day). Similarly, rates of
      whole body protein synthesis, degradation, and leucine oxidation after long-term
      therapy with the VLPD regimen did not differ from baseline values, and neutral BN
      was maintained by a marked suppression of amino acid oxidation and postprandial
      inhibition of protein degradation. This is the first evidence that the
      compensatory changes in whole body protein turnover activated in response to
      dietary protein restriction are sustained during long-term therapy.

PMID- 7733267
TI  - Metabolic alterations associated with the antidiabetic effect of beta 3
      adrenergic receptor agonists in obese mice.
AB  - Treatment of obese (ob/ob) mice with the beta 3-adrenergic receptor (beta 3-AR)
      agonist BRL-35135 (1 mg.kg body wt-1.day-1 for 20 days) normalized plasma glucose
      levels and significantly decreased plasma insulin and nonesterified fatty acid
      levels. The time frame for the hypoglycemic effect, which reached a maximum after
      10 days of treatment, paralleled an increase in brown adipose tissue DNA and
      protein content. The basal level of mRNA for the beta 3-AR and mitochondrial
      uncoupling protein was found to be markedly decreased in the ob/ob animals
      relative to the lean group. Chronic treatment of ob/ob mice for 20 days resulted
      in a twofold increase in beta 3-AR mRNA and a fivefold increase in uncoupling
      protein mRNA in brown adipose tissue relative to the placebo group. These
      findings indicate that chronic treatment of ob/ob animals with a beta 3-AR
      agonist results in proliferation of brown adipose tissue, with an upregulation of
      the beta 3-AR, which is associated with a decrease in plasma glucose, insulin,
      and nonesterified fatty acid levels.

PMID- 7733268
TI  - Orchidectomy and NMDA increase GnRH secretion as measured by push-pull perfusion
      of rat anterior pituitary.
AB  - Using push-pull perfusion to measure concentrations of gonadotropin-releasing
      hormone (GnRH) in the extracellular fluid of the anterior pituitary gland of the
      male rat, we have measured GnRH release at specific times before and after
      castration and in response to acute administration of N-methyl-D-aspartate
      (NMDA). After castration (7 days), mean GnRH levels were substantially increased
      (4.3-fold) compared with intact controls (0.94 +/- 0.16 vs. 0.22 +/- 0.08 pg/10
      min, respectively, P < 0.05) due to an increase in both the frequency and
      amplitude of GnRH pulses. Testosterone partially reduced GnRH release (0.62 +/-
      0.10 pg/10 min). NMDA induced a rapid increase in plasma luteinizing hormone (LH)
      in both intact and castrated rats and increased GnRH concentrations in the
      perfusion samples (P < 0.05). There was no change in LH release induced by two
      doses of injected GnRH (5 and 25 ng/100 g body wt) 2 days after castration, but
      by 6 days after castration the response to both doses was significantly
      increased. These results demonstrate that GnRH release in the male rat is acutely
      increased by NMDA and is chronically increased after orchidectomy. Increased
      pituitary sensitivity to GnRH also contributes to the hypersecretion of LH after
      castration, particularly at longer times after removal of testosterone negative
      feedback.

PMID- 7733269
TI  - Evidence for regulated coupling of A1 adenosine receptors by phosphorylation in
      Zucker rats.
AB  - Studies were designed to find the molecular basis for previous observations that
      lipolysis is less active and A1 adenosine receptor signaling is more active in
      adipocytes from obese than from lean Zucker rats. With quantitative immunoblot
      procedures for detection, Gi alpha 1 and Gs alpha 45 levels were found
      anomalously low in obese compared with lean membranes (50 and 30%, respectively),
      but other G alpha subunit levels were normal. However, the sensitivity of the
      receptor-Gi protein to GTP was about 5- to 10-fold higher in obese compared with
      lean membranes when assessed from 1) the ability of GTP to inhibit forskolin
      stimulated adenylyl cyclase in the presence of an adenosine receptor agonist and
      2) the ability of a nonhydrolyzable guanine nucleotide analogue to alter A1
      adenosine receptor agonist binding. Alkaline phosphatase treatment of isolated
      adipocyte membranes from obese but not lean animals decreased guanine nucleotide
      sensitivity of agonist binding. Surprisingly, solubilized adipocyte A1 adenosine
      receptors from all animals exhibited the same high sensitivity to guanine
      nucleotides as that of intact obese membranes, and this high sensitivity could be
      decreased 20-fold by treatment with alkaline phosphatase. These data suggest that
      protein phosphorylation may regulate coupling of the A1 adenosine receptor in rat
      adipocyte membranes.

PMID- 7733270
TI  - Glutamine-glutamate exchange between placenta and fetal liver.
AB  - The hypothesis that glutamine shuttles nitrogen between placenta and fetal liver
      via interconversion with glutamate was explored by infusing L-[1,2-13C2]glutamine
      in six fetal sheep chronically catheterized for sampling of the umbilical and
      hepatic circulations. Fetal plasma glutamine disposal rate was 19.9 +/- 1.3
      mumol.min-1.kg fetus-1. Entry of glutamine from the placenta accounted for
      approximately 60% of the total glutamine entry rate in fetal plasma. Glutamine
      was taken up by fetal liver, and 45.3 +/- 7.9% of the glutamine taken up was
      released as glutamate. The fetal liver released large quantities of glutamate, as
      evidenced by a sixfold increase in plasma glutamate concentration in the blood
      flowing through the left hepatic lobe and a hepatic glutamate output-to-O2 uptake
      molar ratio of 0.149 +/- 0.013. In conjunction with a previous study of fetal
      glutamate metabolism, these data demonstrate that glutamine entering the fetal
      circulation is converted to glutamate by the fetal liver at a rate of
      approximately 3-4 mumol.min-1.kg fetus-1.

PMID- 7733271
TI  - Assessment of extracellular glucose distribution and glucose transport activity
      in conscious rats.
AB  - The effects of insulin on extracellular glucose distribution and cellular glucose
      transport activity were studied by simultaneously analyzing the plasma kinetics
      of L-[1-14C]glucose and 3-O-[3H]methylglucose after an intravenous injection
      during saline or insulin infusion (euglycemic glucose clamp) in conscious rats (n
      = 7 for each). The time profiles of plasma L-glucose were almost superimposable
      in the two protocols, and compartmental analysis showed that neither distribution
      volumes nor distribution rate constants were affected with insulin (P > 0.05 for
      all), suggesting that glucose distribution within the extracellular space was not
      influenced with insulin. In contrast, the time profile of plasma 3-O
      methylglucose (3-MG) was markedly altered with insulin; the initial decrease was
      much faster during insulin infusion than during saline infusion, indicating
      stimulation of 3-MG transport into intracellular spaces with insulin. The 3-MG
      data were analyzed using a comprehensive model separately describing
      extracellular distribution and cellular transport of 3-MG by incorporating
      information on extracellular distribution kinetics obtained from L-glucose data.
      The combined L-glucose and 3-MG kinetic analysis precisely estimated insulin's
      effect in vivo to stimulate glucose transport into and out of intracellular
      spaces. We conclude that 1) insulin does not affect extracellular glucose
      distribution kinetics or volumes in conscious rats and 2) insulin's effects on
      cellular glucose transport in vivo can be assessed by simultaneous analysis of
      plasma L-glucose and 3-MG kinetics.

PMID- 7733272
TI  - Modulation of in vivo insulin action by dietary protein during pregnancy.
AB  - Rats were provided with a standard 20% protein diet or an isocaloric 8% protein
      diet from day 1 of gestation and were studied on day 19 of pregnancy. Fetal
      numbers per dam were unchanged, but total fetal weight at day 19 of gestation was
      reduced by 10% (P < 0.001) in the 8% protein group. In the basal state,
      endogenous glucose production (Ra) and muscle glucose uptake/phosphorylation were
      not significantly affected by dietary protein content. The glucose infusion rate
      required to maintain glycemia and Ra during euglycemic-hyperinsulinemic clamp
      (insulin infusion rate of 4.17 mU.kg-1.min-1) were reduced in the 8% protein
      group by 17% (P < 0.05) and 76% (P < 0.001), respectively. Suppression of Ra by
      insulin was not significant in the 20% protein group. Insulin-stimulated glucose
      disappearance (Rd) was 24% lower (P < 0.001) in the 8% protein group (25.0 +/-
      0.8 mg.min-1.kg-1) than in the 20% protein group (32.7 +/- 0.5 mg.min-1.kg-1).
      The overall increment in muscle glucose utilization index (mean of 6 muscles)
      elicited by insulin was impaired by 38.1 +/- 4.0%. Insulin suppressed
      nonesterified fatty acid concentration (NEFA) by 83% (P < 0.001) and plasma
      triacylglycerol concentration (TAG) by 67% (P < 0.05) in the 20% protein group
      but evoked only a 43% (P < 0.01) decline in plasma NEFA and did not significantly
      suppress plasma TAG in the 8% protein group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733273
TI  - Glutamine prevents downregulation of myosin heavy chain synthesis and muscle
      atrophy from glucocorticoids.
AB  - The aims of this study were to determine whether glutamine infusion prevents the
      decline in protein synthesis and muscle wasting associated with repeated
      glucocorticoid treatment. Hormone (cortisol acetate, 100 mg.kg body wt-1.day-1)
      and vehicle (carboxymethyl cellulose)-treated female rats were infused with
      either saline or glutamine (240 mM, 0.75 ml/h) for a 7-day period. Glutamine
      infusion attenuated the decline of plantaris muscle glutamine concentration (3.0
      +/- 0.2 vs. 2.3 +/- 0.2 mumol/g) and prevented > 70% of the total muscle mass
      losses due to the glucocorticoid injections. Fractional synthesis rates of myosin
      heavy chain (MHC) and total protein were determined after constant [3H]leucine
      infusion from the leucyl-tRNA precursor pool, which was similar in all groups
      (range 4.8 +/- 0.5 to 6.3 +/- 0.4 disintegrations.min-1.pmol-1). MHC synthesis
      rates (%/day) in plantaris muscles were reduced to approximately 40% of controls
      (4.2/9.4). Although glutamine had no effect on MHC synthesis in vehicle-treated
      animals (10.1/9.4), it prevented 50% (7.6/4.2) of the hormone-induced decline in
      MHC synthesis rates. The same results were obtained with total protein synthesis
      measurements. Changes in muscle mass did not appear related to estimates of
      protein breakdown. In conclusion, these data show that glutamine infusion is
      effective therapy in counteracting glucocorticoid-induced muscle atrophy. Atrophy
      attenuation appears related to maintaining muscle glutamine levels, which in turn
      may limit the glucocorticoid-mediated downregulation of MHC synthesis.

PMID- 7733274
TI  - Influence of valine flooding on channeling of valine into tissue pools and on
      protein synthesis.
AB  - Rates of valine incorporation into protein were measured under control and valine
      "flooding" conditions and included correction for the degree of recycling of
      unlabeled valine derived from the steady-state breakdown of tissue protein into
      the precursor pool (tRNA bound). The correction factor lambda, which is the ratio
      of the steady-state specific activity of valine in the tissue tRNA-bound pool to
      that in the arterial plasma, was determined for each of the tissues. In controls,
      values of lambda ranged from 0.31 in adrenals to 0.54 in heart; in flooded
      animals, values were higher, but only in liver was the value of lambda close to
      1.0. In control and flooded rats, rates of protein synthesis were highest in
      liver and adrenals and lowest in skeletal muscle, with intermediate values in
      brain and heart. Flooding resulted in increased rates of protein synthesis in
      liver and decreased rates in adrenals. Rates of protein synthesis in brain,
      heart, and skeletal muscle were not statistically significantly affected by
      flooding.

PMID- 7733275
TI  - Growth hormone-binding protein in normal mice and in transgenic mice expressing
      bovine growth hormone gene.
AB  - The levels and characteristics of growth hormone (GH)-binding protein (GHBP) and
      the distribution of GH in peripheral circulation between the free and the bound
      fractions were studied in three lines of transgenic mice with various degrees of
      overexpression of bovine (b) GH gene. Two serum fractions bound GH specifically:
      one with low affinity and high capacity (GHBPI) and one with high affinity and
      low capacity (GHBPII). The GHBP binding capacity in normal mice (both sexes),
      transgenic male mice that express the metallothionein-I-hybrid bGH genes,
      transgenic female mice that express phosphoenolpyruvate carboxykinase (PEPCK)-bGH
      hybrid genes (PEPCK-bGH-1), and transgenic PEPCK-bGH-5 animals was 1.1 +/- 0.2,
      2.0 +/- 0.1, 3.0 +/- 0.1, and 3.9 +/- 0.6 pmol/ml serum, respectively. The amount
      of GH bound to GHBP in transgenic animals vs. normal siblings was increased 1.8-,
      2.5-, and 3.9-fold in these three lines. Consequently, the levels of GH-GHBP
      complexes in the circulation of PEPCK-bGH-1 transgenic mice were increased
      approximately 10-fold. Specific GHBP radioimmunoassay confirmed a threefold
      increase in GHBP in PEPCK-bGH-1 transgenic animals. The levels of GHBP were not
      significantly correlated to serum GH within or between lines, perhaps due to
      elevation of serum GH in PEPCK-bGH mice above the level producing maximal
      response. From these and previous studies, we conclude that life-long exposure to
      supranormal GH levels leads to major shifts in GH binding in the circulation and
      in the GH target organs.

PMID- 7733276
TI  - High-fat feeding alters the response of rat PDH complex to acute changes in
      glucose and insulin.
AB  - The activity of the pyruvate dehydrogenase complex (PDHC) was studied in tissues
      of controls and insulin-resistant fat-fed rats (FFR) both in the fed state and in
      overnight fasted animals after the induction of short-term changes in plasma
      insulin by an intravenous glucose load. Significant responses by the PDHC to the
      glucose challenge were seen in heart and white adipose tissue (WAT) in controls
      with smaller changes in brown adipose tissue (BAT) and quadriceps muscle (QM) and
      no change in liver. Reduced PDHC responses and lower fed values were seen in
      heart and BAT of FFR. The response in WAT of FFR was prolonged with no change in
      the PDHC response in QM. Plasma nonesterified fatty acids (NEFA) were decreased
      in response to the glucose load with no differences between controls and FFR.
      Tissue triglyceride levels were higher in liver and QM but not heart of FFR.
      These results show differential tissue PDHC responses to short-term changes in
      plasma insulin. The decreased PDHC activity in some tissues of the fat-fed
      animals despite the lack of change in plasma NEFA, together with the triglyceride
      accumulation seen in some tissues but not others, suggests that local
      intracellular fatty acid metabolism is important in the regulation of
      intracellular glucose oxidation.

PMID- 7733277
TI  - Cold exposure attenuates effects of secretagogues on serum prolactin and growth
      hormone levels in male rats.
AB  - The stimulatory effect of morphine, dexmedetomidine (an alpha 2-adrenoceptor
      agonist), 1-(3-chlorophenyl)-piperazine (m-CPP, a 5-HT1B agonist), U-50488H (a
      kappa-opioid receptor agonist), pimozide (a dopamine antagonist), and restraint
      stress on prolactin and growth hormone (GH) secretion was compared during cold
      exposure (4 degrees C) and under basal conditions (30 degrees C) in male rats.
      Rectal temperature was also measured. The stimulatory effect of morphine,
      dexmedetomidine, m-CPP, and partially U-50488H on prolactin secretion was
      attenuated in rats kept at 4 degrees C. Cold exposure did not abolish prolactin
      release induced by pimozide and restraint stress. Cold exposure also antagonized
      the effect of morphine and dexmedetomidine on GH secretion. The stimulatory
      effect of morphine on prolactin and GH secretion was restored in the warm
      environment despite the sustained hypothermia. Cold exposure blocked the
      stimulatory effect of morphine on prolactin secretion in rats that were tolerant
      to the hypothermic effect of morphine. Thus hypothermia caused by morphine,
      dexmedetomidine, and m-CPP during cold exposure is not the sole factor in the
      antagonistic effect of cold. We suggest that cold exposure releases some
      compound(s) modulating hypothalamic neural pathways.

PMID- 7733278
TI  - A simulation model for glucose kinetics and estimates of glucose utilization rate
      in type 1 diabetic patients.
AB  - A glucose kinetic model is described that contains insulin-independent and
      insulin-dependent pathways of glucose uptake and includes a saturating flux term
      for glucose transport into the cells by the glucose transporters. The rate of
      glucose utilization was estimated in control subjects and diabetic patients by
      use of a bolus of [3-3H]glucose. Diabetic patients were studied after three
      regimens of insulin therapy: 1) after 24 h of insulin withdrawal, 2) after
      conventional insulin therapy, and 3) after an overnight insulin infusion such
      that plasma glucose was maintained between 4 and 6 mmol/l. In addition, the model
      was used to simulate published results from glucose clamp experiments with a
      range of glycemic levels and insulin concentrations. Estimates of glucose
      utilization flux in diabetic patients and model simulation suggest that high
      plasma glucose concentrations in uncontrolled diabetic patients can be attributed
      to a high glucose production rate by the liver associated with a reduction in
      glucose metabolic clearance rate due to relative saturation of the available pool
      of glucose transporters.

PMID- 7733279
TI  - Mathematical model of beta-cell glucose metabolism and insulin release. I.
      Glucokinase as glucosensor hypothesis.
AB  - To quantitatively test the theory that glucokinase controls the rate of glucose
      metabolism and therefore the rate of insulin secretion, a minimal mathematical
      model of glycolysis in the pancreatic beta-cell was developed. The model
      represents our current hypothesis of how the normal beta-cell transduces the
      glucose signal. In this report, the model was used to address questions regarding
      the control strength of transport, hexokinase, glucose-6-phosphatase, and
      phosphofructokinase in the metabolism of glucose. The hypothesis that fructose 6
      phosphate and a protein regulator modulate glucokinase activity was evaluated by
      simulation analysis, as was the possibility that glucose-6-phosphatase, working
      in concert with phosphofructokinase, can modulate the glucose-sensing system. It
      was found that, in the absence of glucose-6-phosphatase, transport, hexokinase,
      and phosphofructokinase do not greatly influence the rate of glucose metabolism
      unless their activities are dramatically altered from the measured values.
      Glucose metabolism was profoundly affected by the activity of glucokinase.
      However, in the presence of glucose-6-phosphatase, the ratio of glucose-6
      phosphatase to phosphofructokinase activities was a very important parameter, and
      this potential control mechanism deserves more attention. The results further
      support the notion that glucokinase is indeed the glucosensor of the beta-cell
      and that modeling the system in toto provides quantitative evaluation needed to
      interpret the experimental tests of hypotheses.

PMID- 7733280
TI  - Quantification of carbohydrate oxidation by respiratory gas exchange and isotopic
      tracers.
AB  - Estimates of glucose oxidation measured by indirect respiratory calorimetry and
      by [U-13C]glucose tracer were compared as a function of respiratory exchange
      ratio (RER) in 14 studies performed on 9 healthy adult subjects. RER was varied
      between 0.7 and 1.04, either by fasting or by infusing glucose. 13C enrichment of
      plasma glucose and expired CO2 were measured by mass spectrometry. The two
      methods gave similar results when the nonprotein respiratory quotient (NPRQ) was
      between 0.76 and 0.90. Glucose oxidation by the tracer method was quantified to
      be higher than that by respiratory calorimetry when NPRQ was < 0.76; it was lower
      than the respiratory calorimetry estimate when NPRQ was > 0.90. The discrepancy
      between the two methods at low RER may represent the contribution of
      gluconeogenesis, whereas, at high RER, the discrepancy may be the consequence of
      lipogenesis. We conclude that respiratory calorimetry and [13C]glucose tracer
      give comparable results only in a narrow range of RER. These data are important
      when the disposal of glucose is compared using these techniques in different
      metabolic states with varying respiratory quotients.

PMID- 7733281
TI  - Central cholinergic and alpha-adrenergic mediation of gastric slow wave
      dysrhythmias evoked during motion sickness.
AB  - Motion sickness is associated with gastric slow wave disruption. Animal models of
      slow wave disturbances show dependence on neural and prostaglandin pathways.
      Roles of these pathways in circular vection-evoked gastric dysrhythmias and
      nausea were tested. Eight volunteers with histories of motion sickness underwent
      vection (60 degrees/s), during which nausea (0 = none to 3 = severe) and
      electrogastrographic parameters were assessed. Tachygastric activity was
      expressed as the signal percentage at frequencies of > 4.5 cycles/min. Circular
      vection induced a maximal nausea score of 2.8 +/- 0 at 513 +/- 66 s. Tachygastric
      activity increased from 18 +/- 2 to 37 +/- 4% (P < 0.05) and peaked before
      maximal nausea. Atropine reduced nausea scores to 0 +/- 0 (P < 0.01) with no
      increase in tachygastric activity (14 +/- 6%). In contrast, the peripheral
      muscarinic antagonist methscopolamine did not reduce tachygastric activity (46 +/
      4%), nausea (1.8 +/- 0.5), or time to maximal tachygastric activity (504 +/- 80
      s) with vection. Phentolamine reduced nausea (1.5 +/- 0.3, P < 0.01) and
      tachygastric activity, and delayed their onset, whereas propranolol and naloxone
      had no effect. Pretreatment with oral indomethacin (50 mg) three times daily for
      3 days had no effect on vection-evoked tachygastric activity or nausea. To
      conclude, circular vection evokes gastric dysrhythmias that correlate temporally
      with maximal nausea and are suppressed by atropine, but not methscopolamine, and
      are reduced by phentolamine. In contrast to other models of slow wave disruption,
      endogenous prostaglandins play no role. Thus central cholinergic pathways mediate
      vection-evoked dysrhythmias with additional modulation by alpha-adrenergic
      pathways.

PMID- 7733282
TI  - Medullary TRH is involved in gastric protection induced by low dose of kainic
      acid into the raphe pallidus.
AB  - The gastroprotective effect of kainic acid microinjected into the raphe pallidus
      (Rpa) at a dose subthreshold to increase acid secretion was investigated in
      urethan-anesthetized rats. Kainic acid (25 pg/30 nl) microinjected into the Rpa
      inhibited by 65.8% gastric damage induced by intragastric ethanol (60%). No
      protection was observed when kainic acid was injected outside of the Rpa. The
      cytoprotective effect was completely abolished by thyrotropin-releasing hormone
      (TRH) antibody microinjected bilaterally (1.3 micrograms/site) into the dorsal
      motor nucleus of the vagus (DMN), indomethacin (5 mg/kg ip), and atropine (0.3
      mg/kg sc). Microinjection of TRH antibody outside of the DMN or of control
      antibody into the DMN did not modify the protective action induced by kainic acid
      into the Rpa. The TRH antibody microinjected alone into the DMN did not alter the
      severity of the ethanol-induced gastric lesions. These data indicate that
      excitation of Rpa neurons by a low dose of kainic acid results in cytoprotection
      against ethanol lesions. Furthermore, this cytoprotection occurs as a result of
      TRH action in the DMN and activation of muscarinic and prostaglandin pathways.

PMID- 7733283
TI  - Intestinal digestion, absorption, and transport of structured triglycerides and
      cholesterol in rats.
AB  - We compared the intestinal absorption of trilinolein (1,2,3-tri-[1-14C]linoleyl
      sn-glycerol) with two different structured triglycerides containing one linoleic
      acid (C18:2) and two octanoic acids (C8:0), 1,3-dioctanoyl-2-[1-14C]linoleyl-sn
      glycerol (2-linoleate) and 1,2-di[1-14C]octanoyl-3-linoleyl-sn-glycerol (1,2
      octanoate), respectively. Lymphatic radioactive lipid output of 2-linoleate
      resembled that of trilinolein rats but remained significantly lower during the
      lipid infusion. Radioactive lipid was recovered along the entire small intestinal
      lumen, with a significantly higher amount of [14C]lipid recovered in the lower
      small intestine and cecum in the 2-linoleate group. Delayed uptake of radioactive
      2-linoleate was not due to poor digestion. In contrast, 1,2-octanoate was
      efficiently digested, and both the free fatty acid (FFA) and the monoacylglycerol
      (MG) containing octanoate were rapidly absorbed. Irrespective of its position on
      the triglyceride molecule, 14C-labeled octanoate was poorly transported into
      lymph. In addition, intestinal luminal and mucosal recovery of [14C]octanoate was
      significantly lower in the 1,2-octanoate group compared with [14C]linoleate
      recovery in the 2-linoleate or trilinolein groups. Total recovery of infused
      radioactive lipid was significantly less in the 1,2-octanoate group than in the 2
      linoleate or trilinolein groups. Thus radioactive octanoate in the form of FFA or
      2-MG was rapidly absorbed and transported via the portal vein. The infusion of
      either 2-linoleate or 1,2-octanoate did not affect the absorption and lymphatic
      transport of cholesterol compared with trilinolein. In summary, the type of the
      fatty acid on the structured triglyceride molecule affects its digestion,
      absorption, and lymphatic transport. Structured triglycerides containing octanoic
      acid in the 1- and 3-positions and linoleic acid in the 2-position may not be
      advantageous to use as a sole source of dietary lipid, but should be supplemented
      with long-chain triglycerides.

PMID- 7733284
TI  - Regulation of system y+ arginine transport capacity in differentiating human
      intestinal Caco-2 cells.
AB  - This study describes the ability of passaged human intestinal Caco-2 cells to
      regulate transport of L-arginine via system y+. Subconfluent and confluent cells
      possessed system y+ activity, as determined by the sodium independence of uptake
      and the pattern of inhibition by amino acid analogues or N-ethylmaleimide.
      Initial rates of arginine uptake via system y+ decreased as the cells advanced
      from the undifferentiated to the differentiated state following culture
      passaging. Furthermore, kinetic analysis of the leucine-insensitive portion of
      uptake indicated that the Caco-2 system y+ transport capacity decreased with cell
      age, dropping from a maximal velocity (Vmax) = 1,094 pmol.mg-1.min-1 [Michaelis
      constant (Km) = 41 microM] in undifferentiated cells 2 days postseeding to Vmax =
      320 pmol.mg-1.min-1 (Km = 37 microM) in confluent cells 9 days postseeding (from
      cells of the same passage). Northern analysis indicated that the levels of a
      single 7.9-kb mCAT-1 mRNA species were relatively constant over the course of
      Caco-2 differentiation and therefore were unsynchronized with the system y+
      relative transport activities. It is concluded that the Caco-2 capacity to
      transport arginine via system y+ may be downregulated by posttransitional
      modifications in confluent cells compared with newly passaged undifferentiated
      cells. These data serve as a well-defined in vitro model for further studies
      regarding regulation of arginine transport in epithelial cells.

PMID- 7733285
TI  - Gastrin mediates the increase in gastric cell growth in uremic rats.
AB  - In a rat model of chronic renal failure, we recently reported that
      hypergastrinemia was associated with increased stomach weight and parietal cell
      and enterochromaffin-like (ECL) cell density. In this study, the role of gastrin
      in mediating trophic effects of uremia on the gastric mucosa was examined by
      chronic immunoneutralization of endogenous gastrin in the sub-total nephrectomy
      uremic rat model. Three weeks after surgery, the rats were uremic (azotemic and
      hypertensive). Uremic rats had a significant increase in corpus mucosal height
      (17%), parietal cell density (14%), ECL cell density (27%), and basal gastric
      mucosal blood flow (63%). These effects were specifically inhibited by chronic
      administration of gastrin-specific monoclonal antibody (5 mg ip every other day)
      in the 3-wk postoperative period. Uremic rats also had an increase in stomach
      weight (23%), corpus mucosal area (8%), arterial blood pressure, and serum
      creatinine and a decrease in body weight. Gastrin immunoneutralization did not
      alter these effects. The findings suggest that elevated levels of endogenous
      circulating gastrin in uremic rats mediate, in part, the trophic response
      observed in the gastric mucosa.

PMID- 7733286
TI  - Identification of CCK-A receptors on chief cells with use of a novel, highly
      selective ligand.
AB  - Functional studies suggest that guinea pig chief cells have both cholecystokinin
      A (CCK-A) and CCK-B receptors (CCK-A-R and CCK-B-R, respectively). However, all
      efforts to directly characterize the specific CCK-A-R using binding have been
      unsuccessful. Recent studies describe specific CCK-A-R agonists such as A-71378
      ([desamino-Nle28,31-(N-methyl)Asp32]CCK heptapeptide]. In the present study, [D
      Tyr-Gly]A-71378 was synthesized, which has > 300-fold selectivity for CCK-A-R and
      can be iodinated. [D-Tyr-Gly]A-71378 was equipotent to A-71378 in stimulating
      pepsinogen release from purified guinea pig chief cells. Binding of 125I-labeled
      [D-Tyr-Gly]A-71378 was saturable and specific. Potencies for inhibiting binding
      were as follows: [D-Tyr-Gly]A-71378 = A-71378 = 4x CCK octapeptide (CCK-8) >
      1,000x des(SO4)-CCK-8, gastrin. In contrast, for 125I-gastrin binding they were
      CCK-8 > gastrin-17-I > des(SO4)-CCK-8 >> A-71378 or [D-Tyr-Gly]A-71378. Binding
      of [D-Tyr-Gly]A-71378 was best fitted by a two-site model. In contrast, 125I
      gastrin binding was fitted with a single-site model. For inhibiting binding of
      125I-[D-Tyr-Gly]A-71378, the CCK antagonists had relative affinities of L-364,718
      >> L-365,260, and the reverse was true with 125I-gastrin. Correlation of binding
      with changes in biological activity suggested low-affinity CCK-A-R were mediating
      these changes. These results demonstrate directly for the first time that guinea
      pig chief cells possess CCK-A-R and CCK-B-R. The pharmacology of these CCK-A-R
      resembles those on other tissues. This novel, highly selective CCK-A ligand
      should be useful because it will identify CCK-A-R when they make up as little as
      0.2% of the total CCK receptor number.

PMID- 7733287
TI  - Nuclear serine protease activity contributes to bile acid-induced apoptosis in
      hepatocytes.
AB  - Glycodeoxycholate (GDC) induces apoptosis in hepatocytes by a mechanism
      associated with DNA cleavage by endonucleases. In many models of apoptosis,
      proteolysis is required prior to DNA cleavage. Our aims were to determine if
      enhanced proteolysis is a mechanism causing GDC-mediated apoptosis. In cultured
      rat hepatocytes exposed to 50 microM GDC for 4 h, nonlysosomal proteolysis
      increased by 65% compared with controls. The serine protease inhibitor N alpha-p
      tosyl-L-lysine chloromethyl ketone (TLCK; 100 microM) reduced cell death from
      apoptosis by 75% after 4 h of treatment with GDC. TLCK also inhibited DNA
      fragmentation. There was a twofold increase in nuclear serinelike protease
      activity during GDC-induced apoptosis accompanied by a 2.5-fold reduction in
      nonnuclear serine protease activity, suggesting translocation of the protease
      from the cytosol to the nucleus. Zn2+, an inhibitor of apoptosis, also inhibited
      nonlysosomal proteolysis and nuclear serinelike protease activity. These novel
      data suggest that nonlysosomal serinelike protease activity contributes to
      hepatocyte apoptosis. These data may be important in understanding apoptosis in
      other cell types and in providing insight into the mechanisms of liver injury
      during cholestasis.

PMID- 7733288
TI  - Disruption of colonic electrolyte transport in experimental colitis.
AB  - The time course of disturbances of distal colonic electrolyte transport during
      experimental colitis in rats was compared with changes in the severity of
      inflammation and epithelial disruption. Colitis was induced by intracolonic
      administration of trinitrobenzenesulfonic acid (TNBS). At time points from 1 day
      to 8 wk thereafter, Na+ and Cl- transport was studied under short-circuited
      conditions in Ussing chambers, three indexes of tissue inflammation were
      measured, and histology was performed. Net absorption of Na+ and Cl- was
      abolished at 1 and 4 days after induction of colitis, but recovered to control
      levels by 1 wk. All unidirectional electrolyte fluxes were elevated at 1 day and
      fell significantly, generally to control levels, by 4 days. The indexes of
      inflammation, tissue myeloperoxidase, and synthetic capacities for prostaglandin
      E2 and leukotriene B4 were all significantly elevated from 1 day to 2 wk post
      TNBS. At 1 and 4 days, there was widespread epithelial necrosis, and
      reepithelialization was consistently seen by 2 wk. In additional studies, 2 wk
      post-TNBS, the short-circuit current response to 3-isobutyl-1-methylxanthine was
      reduced compared with controls. These data suggest that abolition of electrolyte
      absorption early in this experimental colitis was largely attributable to
      epithelial damage. Despite demonstrable tissue inflammation 2 wk post-TNBS, basal
      electrolyte transport was not impaired, while the colitic epithelium was
      hyporesponsive to a Cl- secretagogue. The data also suggest that gross barrier
      function was restored prior to reepithelialization.

PMID- 7733289
TI  - Production and metabolism of dopamine and norepinephrine in mesenteric organs and
      liver of swine.
AB  - Concentrations of catecholamines and their metabolites in plasma entering and
      exiting mesenteric organs, liver, and kidneys were examined to assess the
      regional production and metabolism of catecholamines in anesthetized swine.
      Higher portal venous than arterial plasma concentrations of norepinephrine and
      its metabolites, 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4
      hydroxyphenylglycol (MHPG), and of dopamine and its metabolites, 3,4
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), indicated
      substantial production of both catecholamines by mesenteric organs, representing
      45-50% of total body production. Most dopamine was not metabolized to
      norepinephrine, suggesting a large nonnoradrenergic contribution to total body
      dopamine production. Concentrations of norepinephrine, DHPG, normetanephrine, and
      MHPG were lower in plasma exiting than entering the liver, whereas concentrations
      of the end-product of norepinephrine metabolism, vanillylmandelic acid (VMA),
      were higher in outflowing than inflowing plasma. Over 94% of the VMA removed by
      the kidneys was produced in the liver, consistent with the hepatic source of this
      metabolite. Removal of DOPAC and HVA by the liver exceeded removal by the kidneys
      or production by mesenteric organs, indicating greater hepatic than renal
      elimination of these metabolites from the body and underestimation of mesenteric
      organ dopamine production based on summed spillovers of dopamine metabolites from
      the liver into the systemic circulation.

PMID- 7733290
TI  - Prolonged ambulatory canine colonic motility.
AB  - Canine gastrointestinal motility is studied at present in animals confined to a
      small cage or sling. The aims of this study were to record colonic activity over
      a 24-h period in eight dogs by an ambulatory method. Motility signals from
      implanted strain gauges were processed and stored via a portable battery-operated
      amplifier and digital recorder housed in a jacket. Ambulant interdigestive
      activity was the same as observed in laboratory experiments, with migrating
      colonic motor complexes (CMCs) and infrequent giant contractions (GCs). Feeding
      caused a multiphasic alteration in motility for 582.1 +/- 18.1 min (mean +/- SE).
      There were four distinct phases. During the "early" (0-2 h) postprandial period,
      phase 1 (mean duration: 55.1 +/- 4.0 min), which was distinguished by CMCs of
      high frequency and elevated amplitude in the proximal colon, and phase 2 (78.2 +/
      6.2 min), which had CMC characteristics similar to those in the interdigestive
      period, occurred. Phase 3 (218.8 +/- 13.6 min), a further period of increased
      motility, and phase 4 (339.1 +/- 14.0 min), characterized by low-amplitude long
      duration CMCs, occurred during the "late" (2 h onward) postprandial response.
      With the exception of phase 3, postprandial phases were not always present
      following food intake, and their expression was markedly influenced by variations
      in meal time and by defecation immediately following feeding. Spontaneous
      defecation was characterized by a variety of motor profiles, with a GC
      accompanying two-thirds of episodes. We conclude that a more complete picture of
      canine colonic motility has been documented because of the development of the
      ambulatory system.

PMID- 7733291
TI  - Ecto-adenosinetriphosphatase in rat small intestinal brush-border membranes.
AB  - Antibodies against the holo ecto-adenosinetriphosphatase (ATPase) of rat liver
      and antibodies against COOH-terminal peptides of the long isoform of this enzyme
      reacted in Western blots with a 105-kDa band from small intestinal brush-border
      membranes. Indirect immunofluorescence revealed reactive proteins predominantly
      at the apical surface of enterocytes with some staining of basolateral membranes
      and of vascular endothelium. Similar results were obtained with monoclonal
      antibodies against HA4, a protein from rat liver closely related to the ecto
      ATPase. Since these results suggested the presence of an ecto-ATPase, ATP
      hydrolysis was studied in intact, right-side-out brush-border membrane vesicles.
      Nearly half of ATP hydrolysis was caused by alkaline phosphatase (AP). Besides
      purine and pyrimidine trinucleotides, AP also hydrolyzed ADP, AMP, pyrophosphate,
      and 4-nitrophenylphosphate. Inactivation of AP by cleavage of its membrane anchor
      and by removal of the Zn2+ necessary for its function left the ecto-ATPase that
      was activated by Ca2+ and Mg2+ and hydrolyzed purine and pyrimidine
      trinucleotides and dinucleotides, but not AMP, pyrophosphate, and 4
      nitrophenylphosphate. These features are characteristic of an ATP
      diphosphohydrolase (EC 3.6.1.5, also called apyrase). The physiological role of
      the small intestinal ecto-ATPase may be the degradation of nutrient nucleotides.

PMID- 7733292
TI  - ATP-dependent bile acid transport across microvillous membrane of human term
      trophoblast.
AB  - The main fate for fetal bile acids is to be transferred to the mother by the
      trophoblast. In this study, ATP-dependent bile acid transport across the maternal
      and the fetal-facing plasma membranes (mTPM and fTPM, respectively) of the human
      trophoblast was investigated. With the use of [14C]glycocholate (GC) and a rapid
      filtration technique, GC transport by mTPM and fTPM was measured in the absence
      or the presence of 3 mM ATP plus an ATP-regenerating system. GC efflux from
      preloaded mTPM or fTPM vesicles was found to be insensitive to ATP. By contrast,
      GC uptake by mTPM, but not by fTPM, was significantly increased (approximately
      threefold) by ATP. This was temperature sensitive and occurred into an
      osmotically reactive space. Kinetic analysis revealed that GC uptake by mTPM was
      saturable and fit the Michaelis-Menten equation both in the absence and in the
      presence of ATP. ATP-dependent transport was not abolished by a protonophore
      (carbonyl cyanide p-trifluormethoxyphenyl hydrazone) together with 100 mM K+ (in
      = out) plus a K+ ionophore (valinomycin). It specifically required hydrolyzable
      ATP, although CTP had a slight stimulatory effect. Neither Na+ nor Cl- (100 mM,
      in = out) was mandatory. Moreover, 100 mM gradients of either Na+ (in << out) or
      Cl- (in >> out) had no effect on ATP-dependent GC uptake. This was inhibited by
      vanadate and bile acid analogues but not by several cholephilic organic anions
      and a variety of adenosine triphosphatase inhibitors. These results provide
      strong evidence for the existence of an ATP-dependent transport system for bile
      acids across the apical membrane of human trophoblast, which may play an
      important role in the control of the overall fetal-maternal bile acid traffic.

PMID- 7733293
TI  - Involvement of capsaicin-sensitive primary afferent fibers in regulation of
      jejunal alanine absorption.
AB  - Capsaicin-sensitive primary afferent fibers (CSPA) in the small intestine
      regulate many functions through the release of peptides and neurotransmitters.
      This study was undertaken to assess the role of CSPA in the regulation of jejunal
      alanine absorption in the rat. In a series of in vivo experiments, the effects of
      the sensory neurotoxin capsaicin on small intestinal alanine absorption were
      evaluated. In vitro experiments were also done to study its effects on alanine
      uptake by isolated jejunal strips and mucosal scrapings. Jejunal alanine
      absorption was reduced by 27% when capsaicin (160 and 800 microM) was perfused
      intraluminally and by 21% when it was applied topically to the cervical vagi. On
      the other hand, bilateral cervical vagotomy and reversible block of vagal CSPA
      increased alanine absorption by 29 and 41%, respectively. In vitro, capsaicin
      reduced alanine uptake by intestinal strips in a dose-dependent manner. Maximal
      inhibition (36.5%) occurred at 400 microM with the mean ineffective concentration
      at 87 microM. Alanine uptake by jejunal mucosal scrapings, however, was decreased
      only by 6.7% when incubated with 1,600 microM capsaicin. These data suggest that
      vagal CSPA exerts a tonic inhibitory effect on alanine absorption and that
      capsaicin's inhibitory effect on alanine absorption is mediated largely by the
      capsaicin-sensitive afferent fibers.

PMID- 7733294
TI  - Chyme transport patterns in human duodenum, determined by multiple intraluminal
      impedancometry.
AB  - To get information about the mechanisms involved in chyme transport during the
      fasting and postprandial states, the novel procedure of multiple intraluminal
      impedancometry was evaluated in 14 healthy subjects (6 during fasting, 8 after a
      test meal). All main features of the migrating motor complex (MMC) cycle were
      determined. During phase II of the MMC cycle and the postprandial period,
      different transport patterns of chyme, termed bolus transport events (BTEs), were
      determined. These were 1) simple long-distance propulsive transport (spreading
      distance > 16 cm), 2) short-distance propulsive transport, and 3) retrograde
      transport. A significantly lower number of BTEs was recorded during fasting than
      postprandially. Short-distance propulsive BTEs predominated during fasting (72%),
      and long-distance propulsive BTEs predominated after the test meal (76%).
      Retrograde BTEs were recorded during fasting (4%) and postprandially (8%). In the
      latter state, complex long-distance propulsive BTEs were also observed (5%),
      consisting of multiple components. A major proportion of gastric contents was
      found to be continuously transported to jejunum. In conclusion, impedancometry
      enables us to determine patterns and parameters of chyme transport during fasting
      and postprandial states.

PMID- 7733295
TI  - Kinetics and uptake in vivo of oxidatively modified lymph chylomicrons.
AB  - The metabolism of oxidized chylomicrons (ox-CMs) was investigated in vivo. CMs
      from rats fed corn, linseed, or fish oil were oxidized by incubation with 2,2'
      azobis(2-amidinopropane)hydrochloride (AAPH) or sodium hypochlorite (NaOCl).
      Oxidized CMs had a rapid phase of clearance, followed by a slow phase. Clearance
      of ox-CMs was decreased for corn oil but increased for linseed and fish oil
      particles. Differences in rats of uptake between CM types or treatment were
      independent of the rate of remnant formation, but were instead a consequence of
      decreased clearance. A greater triglyceride-to-cholesteryl ester ratio in liver
      suggested that there was less lipolysis of ox-CM triglyceride prior to uptake.
      Hepatic uptake of ox-CMs was decreased, whereas there was increased uptake in
      spleen. However, the uptake by Kupffer cells of ox-CMs was 43% of total liver
      uptake after AAPH treatment and 59% after NaOCl treatment, compared with 21% for
      control CMs. Collectively, our data show that oxidation can have differential
      effects on the rate of clearance of CMs and that ox-CMs are preferentially
      cleared by the reticuloendothelial system.

PMID- 7733296
TI  - An age-related difference in hyperoxia lethality: role of lung antioxidant
      defense mechanisms.
AB  - The role of animal age in the lethal response to > 98% oxygen has been
      extensively studied, with the observation that neonatal rats were resistant while
      mature animals were sensitive. Antioxidant enzymes increased during the oxygen
      exposure in neonatal but not in mature rats, suggesting they were important in
      the age-related toxicity difference. Because no studies had compared the response
      of mature and old rats to hyperoxia, we exposed Fischer 344 rats, aged 2 and 27
      mo, to > 98% oxygen. Unexpectedly, the old rats lived significantly longer than
      young, 114 and 65 h, respectively. No histopathological differences were found to
      explain the results. Of the antioxidants, only glutathione peroxidase (GPx)
      activity was higher in the lungs of nonexposed old rats. Superoxide dismutase
      (SOD) was higher in the young, results opposite those expected if SOD was
      important in the lethality difference. No antioxidant induction occurred in the
      old oxygen-exposed rats. These results suggest that although there may be a role
      for GPx, mechanisms in addition to antioxidant protection and inflammation are
      likely responsible for the age-related difference in hyperoxia lethality.

PMID- 7733297
TI  - Evidence of Na-K-Cl cotransport in airway smooth muscle.
AB  - The presence of the Na-K-Cl cotransporter in airway smooth muscle was
      investigated by measuring 86Rb+ (as a marker for K+) and 36Cl- fluxes in the
      guinea pig trachealis. K+ uptake consisted of 1) a bumetanide- and furosemide
      sensitive component, 2) a ouabain-sensitive component, and 3) a bumetanide- and
      ouabain-insensitive component. Bumetanide and furosemide inhibited K+ uptake with
      IC50s of 0.18 and 5.6 microM, respectively. Bumetanide-sensitive K+ uptake was
      reduced by the isosmotic replacement of extracellular Na+ and Cl- with choline
      and I-, respectively. Bumetanide caused a reduction in Cl- uptake, and the ratio
      of bumetanide-sensitive K+ to Cl-uptake was approximately 1:1.75. Bumetanide
      caused a decrease in 86Rb+ efflux, suggesting that the Na-K-Cl cotransporter
      mediates both K+ influx and efflux in airway smooth muscle. Ouabain caused an
      increase in bumetanide-sensitive 86Rb+ efflux from the guinea pig trachealis,
      which was prevented by exposure to a low-Na+ medium, suggesting that Na-K pump
      inhibition stimulates outward Na-K-Cl cotransport as a result of an increase in
      intracellular Na+ content.

PMID- 7733298
TI  - Modulation of Ca2+ influx by a mediator released from human tracheal epithelial
      cells exposed to ozone in vitro.
AB  - Intracellular free Ca2+ ([Ca2+]i) plays a vital role both in maintaining normal
      cellular function and in cell killing. Few studies have been published regarding
      its role in ozone (O3)-induced health effects. This study investigated the effect
      and mechanism of O3 exposure on [Ca2+]i in human tracheal epithelial (HTE) cells.
      HTE cells grown on Costar Transwell inserts with a liquid-gas interface were
      exposed to 0, 0.05, 0.1, 0.2 and 0.4 ppm O3 at 37 degrees C for 1 h. After
      exposure, [Ca2+]i was measured using the fluorescent dye Fluo 3. O3 at 0.4 ppm
      produced a significant increase in [Ca2+]i, and the increases in [Ca2+]i were
      blocked by verapamil and 8-(diethylamino)-octyl-3,4,5,-trimethoxybenzoate (TMB
      8). These results suggest that the O3-induced [Ca2+]i elevation may involve both
      Ca2+ release from internal stores and Ca2+ influx across the plasma membrane.
      Furthermore, both buffer and cell lysate of HTE cells exposed to 0.4 ppm O3
      caused a rapid increase in [Ca2+]i of THP-1 human phagocytic monocytes, but the
      buffer and lysate from air exposed cells did not. These results suggest that O3
      exposure causes HTE cells to release a diffusible mediator from the empty Ca(2+)
      storing organelle and may be responsible for the sustained and persistent [Ca2+]i
      elevation in HTE cells exposed to 0.4 ppm O3.

PMID- 7733299
TI  - Human CC10 gene expression in airway epithelium and subchromosomal locus suggest
      linkage to airway disease.
AB  - The CC10 gene encodes the Clara cell 10-kDa protein, which is expressed in airway
      epithelial cells. Quantification of CC10 gene expression in freshly isolated
      human proximal airway epithelial cells demonstrated very high mRNA levels,
      approximately fivefold greater than gamma-actin mRNA, and in situ hybridization
      localized CC10 mRNA to nonciliated airway epithelial cells. Sequence analysis
      demonstrated that the human CC10 gene is comprised of three short exons separated
      by a long first and short second intron, and with a 5' flanking region typical of
      a regulated gene. Three Alu repeats were observed in intron 1 and one in intron
      2. Two polymorphic regions within the introns were identified. First, a
      microsatellite was localized 5' to the third Alu repeat in intron 1 with a
      variable number of 4- and 5-base pair (bp) repeats and a heterozygosity of 0.71.
      Second, in 3% of the 168 chromosomes examined, there was the insertion of a human
      specific Alu repeat in intron 2, 45 bp 3' to the exon 2-intron junction. In three
      Centre d'Etude du Polymorphisme Humain families, meiotic breakpoint analysis
      using these two polymorphic loci localized the CC10 gene to 11 p12-q13 between
      markers D11S16 and D11S97, a region recently linked to atopy and to the beta
      subunit of the high-affinity immunoglobulin E receptor. The observations in the
      present study of high-level expression of the CC10 gene in the epithelium of
      conducting airways and a subchromosomal localization of the gene to a region
      potentially linked to inflammatory airway disease, together with the reported
      anti-inflammatory and immune-modulating properties of the protein, suggest the
      CC10 gene product may be important in modulating inflammation within the airways.
      If so, the highly heterozygous microsatellite described in the present study
      should facilitate analysis of a possible linkage of the CC10 gene with an
      inherited susceptibility to asthma.

PMID- 7733300
TI  - Variability in distribution and populations of gap junctions in ferret trachea
      during postnatal development.
AB  - Immunocytochemical probes have been used to characterize gap junction
      distribution in the postnatal ferret trachea by epifluorescence and by laser
      scanning confocal and electron microscopy. A battery of antibodies directed
      against fragments of different connexins localized beta 1- and beta 2-gap
      junction antigens (connexins 32 and 26, respectively) at the intercellular
      borders of the superficial epithelium while alpha 1-gap junction antigen
      (connexin 43) was localized to the loose connective tissues. Gap junction
      labeling in the superficial epithelium declined in the first weeks of life but
      persisted in the developing submucosal glands to the weanling stage. Localization
      of the alpha- and beta-antigens was specific for connective tissues and
      epithelial layers, respectively. These observations suggest that communication
      competence is an important component of early development in the mammalian
      airways.

PMID- 7733301
TI  - Corticosteroids increase secretory leukocyte protease inhibitor transcript levels
      in airway epithelial cells.
AB  - Secretory leukocyte protease inhibitor (SLPI) is the predominant antiprotease of
      the conducting airways and may play a role in reducing airway inflammation. In
      this study, the effect of corticosteroids used in the treatment of inflammatory
      airway disease on SLPI transcript levels was investigated. When human airway
      epithelial cells (9HTEo-) were treated continuously with 10 nM fluticasone
      propionate, SLPI transcript levels increased within 12 h, with maximal transcript
      accumulation occurring at 24-48 h. Several corticosteroids (0.1-1,000 nM) were
      compared, and the following potency in increasing SLPI transcript levels was
      observed: fluticasone > triamcinolone > or = dexamethasone > methylprednisolone >
      hydrocortisone. Fluticasone, the most potent corticosteroid, increased SLPI
      transcript levels at doses as low as 0.1 nM, whereas hydrocortisone, the least
      potent corticosteroid, was effective at 100 nM. Fluticasone-induced increases in
      SLPI transcript levels were inhibited by cycloheximide, suggesting protein
      synthesis may be required for this response. Because proteases are likely to be
      present when corticosteroids are administered therapeutically, we examined the
      interaction between elastase and fluticasone and found they act synergistically
      to increase SLPI transcript levels. Our findings suggest that corticosteroids may
      exert their antiinflammatory effects in part by increasing airway epithelial cell
      SLPI production.

PMID- 7733302
TI  - Characterization of endothelin receptors in newborn piglet lung.
AB  - Endothelins (ET-1, ET-2, and ET-3) cause dilation and constriction as a result of
      binding to different ET receptors. ETA receptor is responsible for the
      vasoconstrictor response, while ETB receptors lead to vasodilation (ETB1) or
      vasoconstriction (ETB2). Although the effects of ETs have been described in the
      neonatal pulmonary vasculature, ET receptors have not been characterized
      extensively. Therefore, in newborn piglets we aimed to characterize ET receptors
      by studying 1) in isolated perfused lungs the effects of ET-1, ET-3, and the ETB
      receptor agonists sarafotoxin S6c (S6c) and BQ-3020 on perfusion pressure with or
      without an ETA antagonist, BQ-123, or an ETB1 antagonist, RES-701-1, and 2) the
      concentration-dependence of ET-1 and ET-3 on their binding to microsomes from
      arteries and veins of piglet lungs. ET-1, ET-3, S6c, and BQ-3020 cause an early
      onset dilation followed by a late-onset constriction. The dilator response to ET
      3 is blunted by RES-701-1 (P < 0.005), while the inhibition of the dilator
      response of ET-1 almost reaches significance (P = 0.06). BQ-123 inhibits
      incompletely (P < 0.05) the constrictor response to ET-1, while it does not alter
      the response to ET-3. This suggests that constriction may follow binding to ETA
      as well as ETB2 receptors. Binding studies reveal that ET receptors are abundant
      in pulmonary vessels. ETA receptors are predominant, but ETB1 and likely ETB2
      receptors are also present. Also, receptor affinities are higher in veins than in
      arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733303
TI  - Functional activation of the cystic fibrosis trafficking mutant delta F508-CFTR
      by overexpression.
AB  - The most common mutation in the gene associated with cystic fibrosis (CF) causes
      deletion of phenylalanine at residue 508 (delta F508) of the gene product called
      CFTR. This mutation results in the synthesis of a variant CFTR protein that is
      defective in its ability to traffic to the plasma membrane. Because earlier
      studies showed delta F508-CFTR retains significant phosphorylation-regulated
      chloride (Cl-) channel activity, processes capable of restoring the mislocalized
      delta F508-CFTR to the correct cellular destination may have therapeutic benefit.
      Here we report one such process that involves overexpression of the mutant
      protein and appears to result in the escape of a small amount of delta F508-CFTR
      to the plasma membrane. In recombinant cells where expression of delta F508-CFTR
      is controlled by the metallothionein promoter, this effect can be brought about
      by treatment with sodium butyrate. Although cAMP-activated Cl- channel activity
      could also be detected in immortalized human airway epithelial cells homozygous
      for the delta F508 mutation at the single cell level, treatment with butyrate did
      not generate a measurable cAMP-stimulated Cl- current in polarized monolayers of
      primary CF airway epithelia. However, the observation that overexpression can
      effect the presence of recombinant delta F508-CFTR at the plasma membrane
      suggests that perhaps other butyrate-like compounds that are more potent and more
      specific for the promoter of the CF gene may be efficacious in alleviating the Cl
      channel defect associated with CF.

PMID- 7733304
TI  - Clearance of surfactant protein B from rabbit lungs.
AB  - To characterize the metabolism of surfactant protein B (SP-B) in vivo, we
      measured the clearance of SP-B from adult rabbit lungs. Purified rabbit SP-B was
      radiolabeled with 125I by the Bolton-Hunter method. Trace amounts of 125I-labeled
      SP-B mixed with [14C]dipalmitoylphosphatidylcholine (DPPC) were given
      intratracheally via a bronchoscope to rabbits 0-16 h before collection of
      alveolar washes (AW). Macrophages were recovered from AW, and lamellar bodies
      (LB) were isolated from lung tissue by differential centrifugation. 125I-SP-B was
      cleared more rapidly from the airspaces and the total lung (half-life 7 h) than
      was DPPC (half-life 11 h in the total lung). There was an approximately threefold
      accumulation of SP-B relative to saturated phosphatidylcholine in macrophages at
      all times. The proportion of 125I and 14C radioactivities in lamellar bodies was
      similar at 2 and 4 h, but there was 14-fold less 125I-SP-B than [14C]DPPC in
      lamellar bodies by 16 h. This loss of SP-B from the lamellar body fraction is
      consistent with less recycling of SP-B. The results demonstrate different
      clearance kinetics of these two components of surfactant and indicate a
      significant role of macrophages in the clearance of SP-B.

PMID- 7733305
TI  - Intracellular pH regulates voltage-dependent Ca2+ channels in porcine tracheal
      smooth muscle cells.
AB  - Changes in CO2 or in pH modify airway smooth muscle contractility. To investigate
      the mechanisms involved, we compared K(+)-induced contractions in porcine
      bronchial rings exposed to different CO2 concentrations and directly measured the
      effects of changes in intracellular (pHi) or extracellular pH (pHo) on Ca2+
      currents (ICa) through voltage-dependent Ca2+ channels (VDC) in porcine tracheal
      smooth muscle cells. Hypocapnia and hypercapnia caused leftward and rightward
      shifts, respectively, in the dose-response to K+ (P < 0.05) but did not change
      the maximum force obtained. Peak ICa (10 mM external Ca2+) elicited by
      depolarizing pulses from -80 mV was maximal [-265 +/- 12 pA (mean +/- SE), n =
      19] at +10 mV. Intracellular acidification decreased the peak ICa at +10 mV from 
      261 +/- 20 pA to -177 +/- 12 pA (P < 0.05, n = 4), while intracellular
      alkalinization increased the peak ICa at +10 mV from -302 +/- 27 pA to -368 +/-
      26 pA (P < 0.05, n = 4). Changes in pHo had little effect on ICa. There was no
      shift in the voltage-dependence of induced ICa with any change. We conclude that
      pHi, but not pHo, directly modulates the entry of Ca2+ into airway smooth muscle
      cells through VDC. This mechanism may contribute to regulation of airway tone by
      CO2.

PMID- 7733306
TI  - Adenovirus-mediated gene transfer to human bronchial submucosal glands using
      xenografts.
AB  - The cystic fibrosis (CF) transmembrane conductance regulator has been localized
      to both submucosal glands and surface epithelium, suggesting that both glandular
      and surface epithelium may be important targets for gene therapy. To determine
      the distribution and efficiency of recombinant adenovirus-mediated gene transfer
      to human airway submucosal glands, an in vivo model was developed by
      heterotopically transplanting human bronchial segments from both normal and CF
      lung tissue into severe combined immunodeficient mice. A serotype 5 E1-deleted
      recombinant adenovirus containing a lacZ reporter gene driven by the
      cytomegalovirus promoter (H5.010CMVlacZ) was used to infect the xenografts.
      Transgene expression was correlated with three factors: 1) viral titer, 2)
      penetration of microspheres, and 3) dwell time of the viral instillate. At viral
      titers ranging from 10(8) to 10(11) plaque forming units/ml, expression of the
      lacZ gene was observed in a subpopulation of epithelial cells within
      approximately 40% of submucosal glands, with more efficient gene transfer to the
      ducts than the secretory tubules. Within individual glands, gene transfer varied
      from < 1% to approximately 20% of submucosal cells, including duct, mucous, and
      serous cells. Adenovirus-sized fluorescent microspheres were found to penetrate
      only some of the submucosal glands, suggesting that the gene transfer efficiency
      to submucosal tubules is due to limited viral particle penetration rather than
      tropism. Gene transfer to surface epithelial cells was inefficient. However, the
      percentage of transduced surface epithelial cells increased from < 1% to 5-10% as
      the dwell time of viral solution was increased from 5 min to 1 h, indicating that
      the time allowed for virus binding and entry is important for gene transfer
      efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733307
TI  - Extracellular nucleotides stimulate leukocyte adherence to cultured pulmonary
      artery endothelial cells.
AB  - Adenosine, ATP, and various nucleotides were examined for their effects on the
      adherence of leukocytes to bovine pulmonary artery endothelial cells.
      Extracellular ATP enhanced adherence of HL-60 cells and human neutrophils to
      endothelial cells in a dose-dependent fashion. Maximal adherence occurred after
      15 min coincubation of ATP and HL-60 cells or neutrophils with endothelial cells.
      ATP stimulation was mediated by direct effects on both HL-60 cells and
      endothelial cells. The potency profile of various nucleotides was ATP = 2-MeSATP
      > beta,gamma-CH2ATP, indicative of a P2y receptor. Interestingly, UTP was as
      potent as ATP in stimulating HL-60 cell adherence, suggesting the presence of a
      pyrimidine nucleotide receptor. Photoaffinity labeling of endothelial cells with
      8-Az-[alpha-32P]ATP showed the presence of two ATP binding proteins of 48 and 87
      kDa. ATP and 2-MeSATP inhibited binding by both proteins. Labeling of the 87-kDa
      protein was inhibited by beta,gamma-CH2ATP, whereas UTP blocked binding by the 48
      kDa protein. Thus photoaffinity labeling experiments support the proposal that
      endothelial cells possess two ATP receptors, one of which is a P2u nucleotide
      receptor. These findings show that extracellular nucleotides enhance leukocyte
      adherence to endothelial cells. Nucleotide release into the extracellular space
      may be one mechanism of exacerbating vascular cell injury relevant to conditions
      such as adult respiratory distress syndrome and septic shock.

PMID- 7733308
TI  - Characterization of the promoter of human pulmonary surfactant protein B gene.
AB  - Pulmonary surfactant protein B (SP-B) is required for normal surfactant function
      and for survival at birth. To further study SP-B gene expression, we sequenced
      genomic clones and examined promoter activity of SP-B DNA fragments by transient
      transfection. A plasmid construct containing human SP-B fragment -1039/+431
      linked to chloramphenicol acetyltransferase (CAT) reporter gene was readily
      expressed in H441 cells, which are derived from a human lung adenocarcinoma, but
      was < 4% as active in Hep G2, HeLa, and Calu 6 cell lines. SP-B promoter activity
      in H441 cells was orientation dependent and increased by linked Rous sarcoma
      virus (RSV) enhancer and was stronger than for thymidine kinase (tk) and RSV
      promoters. Deletional mapping of the 5' flanking region with exonuclease III
      suggested nonspecific negative (-811/-1039)- and positive (-453/-641)-control
      regions and a cell-specific enhancer region at -208 to -54. When a fragment from 
      403 to -35 base pairs (bp) was placed upstream or downstream of tkCAT, in either
      orientation, expression in H441 cells but not other cell lines was increased 4-
      to 28-fold relative to tkCAT. Deletional analysis of the 3' terminus indicated a
      requirement for at least 7 bp 3' of the transcription start site. Promoter
      activity was strongly inhibited in a dose-dependent fashion by phorbol ester,
      with responsiveness mapped to bp -208/-54, but was not responsive to
      glucocorticoid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733309
TI  - Postischemic thyroxin stimulates renal mitochondrial adenine nucleotide
      translocator activity.
AB  - Postischemic thyroxin (T4) enhances restitution of cellular ATP and accelerates
      recovery of renal function. This effect is not related to global improvement in
      cell integrity. To determine the mechanism by which recovery of cellular ATP is
      enhanced, the effect of T4 on mitochondrial ATP production was evaluated using
      specific inhibitor stop assays for mitochondrial phosphate transport and ADP
      translocator activity. Rats were subjected to 45-min renal ischemia and given
      normal saline (NS, 0.5 ml) or T4 (20 micrograms/kg) during the reflow period. By
      30-min reflow; the values for apparent endpoint of phosphate transport (PiTm,
      nmol Pi/mg mitochondrial protein) had recovered to rates seen in nonischemic
      animals (10.3 +/- 0.9) and remained stable at 120 min. T4 treatment did not
      affect PiTm. In contrast, the apparent endpoint of ADP transport (ADPTm, nmol
      ADP/mg mitochondrial protein) was dramatically decreased in NS rats at 30-min
      (6.7 +/- 0.5) and 120-min (13.7 +/- 1.0) reflow compared with nonischemic control
      rats (24.7 +/- 2.4). T4 significantly improved ADPTm by 30 min (10.1 +/- 0.6, P <
      0.05). By 120 min T4 stimulated ADPTm (37.7 +/- 5.2, P < 0.05) to exceed
      nonischemic control values. These data suggest the following: 1) postischemic
      mitochondrial PiTm recovers to control values by 30 min of reflow; 2) T4 does not
      augment PiTm; 3) renal ischemia causes a dramatic decrease in mitochondrial
      ADPTm; 4) postischemic T4 significantly enhances mitochondrial nucleotide
      transport at 30-min reflow; 5) by 120-min reflow, T4 rats have ADPTm which
      exceeds control values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733310
TI  - Drawbacks of the constant-infusion technique for measurement of renal function.
AB  - We investigated the validity of the steady-state constant infusion method (CIM),
      in which quantitative urinary recovery and constant plasma concentrations of the
      solute infused are required. Successive 3-h clearances of inulin and p
      aminohippuric acid (PAH) were determined for 27 h in 25 patients with renal
      disease. Results were compared with the standard method of bladder clearance
      (StM) and with a modified CIM (ModCIM). The 24-h urinary recovery was incomplete
      for both inulin and PAH. Mean 24-h ModCIM inulin clearance overestimated StM by
      4.5 ml.min-1 x 1.73 m-2 (range 0-9, P < 0.001) independent of the extent of renal
      impairment and pointed to slow distribution and/or extrarenal clearance of
      inulin. For PAH, the difference between ModCIM and StM clearance was related to
      the average PAH clearance by ModCIM and StM (r = 0.78). Furthermore, neither
      plasma inulin nor PAH became completely constant, because of the circadian rhythm
      in renal function. In conclusion, the conditions of the steady-state CIM
      technique are not fulfilled, and the method is not suitable for accurate
      measurement of inulin and PAH clearance, especially when the clearance is low.

PMID- 7733311
TI  - Beta-adrenergic receptor function in rat proximal tubule epithelial cells in
      culture.
AB  - The adrenergic system is important in regulating proximal tubule sodium
      reabsorption. Although alpha-adrenergic receptors have been identified in
      proximal tubules, the presence and function of beta-adrenergic receptors (BAR) in
      proximal tubules is less certain. The purpose of our study was to determine
      whether functional BAR are present on apical or basolateral surfaces of proximal
      tubule epithelial cells (PTEC) of rat kidney. We specifically focused on BAR
      coupling to adenylate cyclase and on differences between requirements for apical
      and basolateral receptor coupling to adenylate cyclase. To determine BAR
      expression and function, primary cultures of rat PTECs were grown on permeable
      supports. Scatchard analysis of 125I-labeled cyanopindolol binding revealed a
      single class of receptors on both apical and basolateral surfaces. Apical
      isoproterenol (ISO) resulted in time- and concentration-dependent increases in
      adenosine 3',5'-cyclic monophosphate (cAMP) that were 50% of responses after
      basolateral ISO. Apical BAR-cAMP coupling was mediated by B1-adrenergic receptors
      (B1AR), since apical cAMP responses were abrogated with apical (but not
      basolateral) B1 but not B2 antagonists. Apical B1AR required endocytosis prior to
      adenylate cyclase activation, since increases in cAMP were prevented by
      phenylarsine oxide or colchicine. B1AR-adenylate cyclase coupling was independent
      of intra- or extracellular calcium, cyclooxygenase metabolites, and protein
      kinase C (PKC) and dependent on Gs guanine nucleotide regulatory protein.
      Prolonged exposure to ISO resulted in time- and concentration-dependent
      homologous desensitization of cAMP responses. Desensitization was independent of
      receptor sequestration, PKA, or PKC. We conclude the following: B1AR are present
      on both apical and basolateral surfaces of rat PTECs.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7733312
TI  - Role of chloride in the variable response of the kidney to cyclooxygenase
      inhibition.
AB  - The role of prostanoids in renal function remains unclear, as inhibitors of
      cyclooxygenase (COX) have contrasting effects. We postulated that these
      inconsistencies were related to differential effects of the prevailing chloride
      concentration on COX-dependent mechanisms. In oncotically perfused rat kidneys,
      in the presence of either high (117 mM) or low (87 mM) chloride with sodium held
      constant, low chloride resulted in a higher glomerular filtration rate (GFR) than
      with high chloride, i.e., 1.2 +/- 0.2 and 0.5 +/- 0.1 ml/min, respectively, for
      the last clearance period. Water and electrolyte excretion and levels of
      immunoassayable prostaglandins were higher with low chloride. Indomethacin (10
      microM) had opposite effects on renal function depending on the chloride levels,
      although prostaglandin release was inhibited similarly. For example, indomethacin
      substantially reduced the elevated urine flow and sodium excretion in the low
      chloride group, which, by the last period, were reduced from 111 +/- 32 to 37 +/-
      3 microliters/min and 8.3 +/- 2.9 to 3.1 +/- 0.6 mu eq/min, respectively, whereas
      the lower urine flow and sodium excretion in the high-chloride group increased
      from 32 +/- 8 to 109 +/- 15 microliters/min and 2.5 +/- 0.8 to 7.1 +/- 1.6 mu
      eq/min, respectively. In summary, inhibition of COX has differential effects
      depending on the prevailing chloride concentration, or conversely, high and low
      chloride have contrasting effects on renal function, which are reversed by COX
      inhibition. We suggest that prohypertensive and antihypertensive COX-dependent
      mechanisms are linked to chloride; the latter is an integral component in the
      development of salt-sensitive hypertension.

PMID- 7733313
TI  - Effect of basolateral or apical hyposmolarity on apical maxi K channels of
      everted rat collecting tubule.
AB  - We are able to evert and perfuse rat cortical collecting tubules (CCT) at 37
      degrees C. Patch-clamp techniques were used to study high-conductance potassium
      channels (maxi K) on the apical membrane. Under control conditions (150 mM Na+
      and 5 mM K+ in pipette and bathing solutions), the slope conductance averaged
      109.8 +/- 6.6 pS (12 channels), and reversal potential (expressed as pipette
      voltage) was +26.3 +/- 2.4 mV. The percent of time the channel spends in the open
      state and unitary current when voltage was clamped to 0 mV were 1.4 +/- 0.7% and
      3.12 +/- 0.42 pA, respectively. In six patches voltage clamped to 0 mV, the
      isosmotic solution perfused through the everted tubule (basolateral surface) was
      exchanged for one made 70 mosmol/kgH2O hyposmotic to the control saline. Open
      probability increased from 0.019 to 0.258, an increase of 0.239 +/- 0.065 (P <
      0.005). In four patches where a maxi K channel was evident, no increase in open
      probability was observed when a hyposmotic saline was placed on the apical
      surface. However, when vasopressin was present on the basolateral surface, apical
      application of hyposmotic saline resulted in a series of bursts of channel
      activity. The average increase in open probability during bursts was (0.055 +/-
      0.017, P < 0.005). We conclude that one function of the maxi K channel located in
      the apical membrane of the rat CCT may be to release intracellular solute
      (potassium) during a volume regulatory decrease induced by placing a dilute
      solution on the basolateral surface or when the apical osmolarity is reduced in
      the presence of vasopressin. These data are consistent with the hypothesis that
      the physiological role of the channel is to regulate cell volume during water
      reabsorption.

PMID- 7733314
TI  - Expression of gastric and colonic H(+)-K(+)-ATPase in the rat kidney.
AB  - Enzymatic and microperfusion studies have indicated that an ATP-dependent H+/K+
      exchange process is present in the collecting duct of the mammalian kidney.
      Immunochemical staining has also provided evidence for expression of a gastric
      type H(+)-K+ adenosine triphosphatase (H(+)-K(+)-ATPase). Rat kidney mRNA was
      probed with use of the polymerase chain reaction (PCR) to determine the presence
      of an H(+)-K(+)-ATPase. cDNA made with mRNA isolated from the kidneys of rats
      maintained on a low-K diet was used as template in PCR reactions with primers
      encompassing the cDNA sequence of the alpha-subunit of the gastric H(+)-K(+)
      ATPase and the 5' and 3' ends of the colonic H(+)-K(+)-ATPase. The resulting
      products, 300-700 bp in size, hybridized with probes directed against either the
      gastric or colonic sequences of the H(+)-K(+)-ATPase. Sequencing of the
      individual PCR products showed identity with the appropriate regions of the alpha
      subunits of the gastric H(+)-K(+)-ATPase and colonic H(+)-K(+)-ATPase. These data
      indicate that the rat kidney expresses mRNAs encoding both gastric and colonic
      H(+)-K(+)-ATPases.

PMID- 7733315
TI  - Acute renal hemodynamic effects of ACE inhibition in diabetic hyperfiltration:
      role of kinins.
AB  - Angiotensin converting enzyme (ACE) inhibitors not only reduce angiotensin II
      (ANG II) levels but also inhibit kinin degradation. The relative roles of ANG II
      and bradykinin in the acute action of ACE inhibitors on renal hemodynamic
      parameters in rats after 3 wk of diabetes were explored using antagonists of the
      ANG II type 1 (AT1) and the bradykinin B2 receptors. Conscious control and
      streptozotocin diabetic male Sprague-Dawley rats were randomized to receive
      vehicle, the ACE inhibitor, ramiprilat, the B2-receptor blocker, HOE-140, the AT1
      receptor blocker, valsartan, or the combination of ramiprilat and HOE-140.
      Systolic blood pressure, glomerular filtration rate (GFR), renal plasma flow
      (RPF), filtration fraction and urinary flow, and sodium excretion were assessed
      before and during treatment. Diabetic animals had higher GFR and a tendency
      toward increased RPF and filtration fraction compared with control animals. Acute
      ramiprilat infusion decreased GFR significantly in diabetic but not in control
      animals. Valsartan and the combination of ramiprilat and HOE-140 reduced blood
      pressure to a similar degree to ramiprilat alone, yet did not reduce GFR. No
      decrease in GFR was observed in any control rat groups. Ramiprilat decreased RPF
      in diabetic rats but increased RPF in control rats. No such effects on RPF were
      observed with valsartan. HOE-140 alone did not influence any renal parameter in
      the diabetic rats. Diabetic rats had increased urinary flow and sodium excretion,
      but these parameters were not influenced by any drug regimen.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7733316
TI  - Hypotonicity increases basolateral taurine permeability in rabbit proximal
      convoluted tubule.
AB  - The permeabilities of the basolateral membrane of rabbit proximal convoluted
      tubule (PCT) to taurine (PTau) and glucose (PGlc) were estimated under control
      and hypotonic conditions using the initial rate of increase in cellular volume
      (CV) induced on isotonic replacement of 40 mM mannitol by one or the other of
      these substrates. Under control conditions, addition of taurine led to an
      increase in CV at an initial rate of 7.1 +/- 1.7%/min, leading to a cell swelling
      of 30.2 +/- 4.8% after 5 min (n = 6). Addition of glucose led to an increase in
      CV at an initial rate of 30.0 +/- 3.8%/min, leading to a cell swelling of 25.7 +/
      3.1% after 5 min (n = 7). After a period of recovery of 5 min in the absence of
      taurine or glucose, a 40 mosmol/kg hypotonic shock induced a cell swelling of
      14.2 +/- 1.3 and 16.1 +/- 5.2%, respectively, followed by an almost complete
      volume regulatory decrease after 5 min. At that time, addition of taurine under
      continuous hypotonicity induced an increase in CV at an initial rate 2.57 +/-
      0.17 times larger than that observed under the isotonic condition (P < 0.005),
      while addition of glucose induced an initial increase in CV identical to that
      observed under the isotonic condition. The increases in CV observed on addition
      of taurine were completely abolished in the absence of sodium under both isotonic
      and hypotonic conditions. The permeability to K+ was also estimated, in the
      absence of sodium, using the initial rate of increase in CV induced on isotonic
      replacement of 40 mM N-methyl-D-glucamine by K+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733317
TI  - Adhesion of calcium oxalate monohydrate crystals to renal epithelial cells is
      inhibited by specific anions.
AB  - Adhesion of urinary crystals to the apical surface of renal tubular cells could
      be a critical step in the formation of kidney stones. The interaction between
      renal epithelial cells (BSC-1 line) and the most common crystal in kidney stones,
      calcium oxalate monohydrate (COM), was studied in a tissue culture model system.
      COM crystals bound to the cell surface within seconds in a concentration
      dependent manner to a far greater extent than did brushite, another calcium
      containing crystal found in urine. Adhesion of COM crystals to cells was blocked
      by the polyanion, heparin. Other glycosaminoglycans including chondroitin sulfate
      A or B, heparan sulfate, and hyaluronic acid, but not chondroitin sulfate C,
      prevented binding of COM crystals. Two nonsulfated polyanions, polyglutamic acid
      and polyaspartic acid, also blocked adherence of COM crystals. Three molecules
      found in urine, nephrocalcin, uropontin, and citrate, each inhibited binding of
      COM crystals, whereas Tamm-Horsfall glycoprotein (THP) did not. Prior exposure of
      crystals but not cells to inhibitory molecules blocked adhesion, suggesting that
      these agents exert their effect at the crystal surface. Inhibition of crystal
      binding followed a linear Langmuir adsorption isotherm for each inhibitor
      identified, suggesting that these molecules bind to a single class of sites on
      the crystal that are important for adhesion to the cell surface. Inhibition of
      crystal adhesion by heparin was rapidly overcome by the polycation protamine,
      suggesting that the glycosaminoglycan regulates cell-crystal interactions in a
      potentially reversible manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733318
TI  - Effect of age on dopaminergic responses to protein feeding.
AB  - Renal excretory responses to protein feeding were compared in nine young (20-26
      yr) and nine elderly (70-89 yr) men. Although protein increased excretion of
      dopamine and serotonin (5-HT, P < 0.001 for both), the basal excretion of
      dopamine and 5-HT was less in old than young men (P < 0.05). Protein increased
      sodium and water excretion in the young; responses in elderly for both were less
      (P < 0.025). Carbidopa markedly suppressed dopamine and 5-HT excretion in both
      young and old men. Carbidopa also attenuated protein-induced natriuresis and
      diuresis and raised serum aldosterone levels in the young but not in the old men.
      These age-related differences in dopamine and 5-HT excretion were not abolished
      by alterations in dietary NaCl. Thus, although dopamine excretion is decreased
      overall in elderly men, sodium and water excretion and aldosterone secretion in
      the old men were unaffected by alterations in dopamine production. These data
      suggest that impaired protein-induced natriuresis in the old men may be due to
      limitations in renovascular responses and that, in young men, dopamine and 5-HT
      may contribute to the protein-induced changes in renovascular function.

PMID- 7733319
TI  - Cloning of a rabbit renal Na-Pi cotransporter, which is regulated by dietary
      phosphate.
AB  - Previously, we isolated a cDNA (NaPi-1) related to a rabbit renal proximal
      tubular Na-Pi cotransporter (A. Werner, M.L. Moore, N. Mantei, J. Biber, G.
      Semenza, and H. Murer. Proc. Natl. Acad. Sci. USA 88:9608-9612, 1991.). In this
      study, we isolated an additional (rabbit renal) cDNA (NaPi-6), which induces Na
      dependent Pi uptake in Xenopus laevis oocytes. Substrate specificity and kinetic
      properties corresponded to those known for rabbit renal brush-border membrane
      (BBM) Na-Pi cotransport. NaPi-6 was cloned by homology using NaPi-2 cDNA, a rat
      renal BBM Na-Pi cotransporter (S. Magagnin, A. Werner, D. Markovich, V. Sorribas,
      G. Stange, J. Biber, and H. Murer. Proc. Natl. Acad. Sci. USA 90: 5979-5983,
      1993). NaPi-6 encodes a protein of 642 amino acids, exhibiting at least eight
      transmembrane domains. NaPi-6 mRNA and protein in kidneys of rabbits fed a low-Pi
      diet (LPD; 0.11% Pi) for 1 wk were increased by 1.5- and 4-fold, respectively,
      compared with those of rabbits fed a high-Pi diet (HPD; 1.20% Pi). This effect
      was correlated with an increase in Na-Pi cotransport of BBM vesicles isolated
      from animals adapted to LPD (2.5-fold with respect to HPD). In contrast, NaPi-1
      mRNA and protein were not altered in response to LPD. Thus rabbit proximal
      tubular BBMs contain two different Na-Pi cotransport systems: NaPi-1 (type I) and
      NaPi-6 (type II). Only the type II transport system seems to be under regulatory
      control in response to low-Pi dietary intake.

PMID- 7733320
TI  - Thyroid hormones regulate development of energy metabolism enzymes in rat
      proximal convoluted tubule.
AB  - Ketone bodies represent preferred energy substrates in the adult rat proximal
      tubule. They are abundant in the plasma of suckling rats and might represent an
      important oxidative substrate for the immature proximal tubule. The postnatal
      development of two enzymes involved in ketone body oxidation pathway, 3-ketoacid
      CoA transferase and acetoacetyl-CoA thiolase, and of citrate synthase and
      carnitine acetyltransferase was studied in microdissected rat proximal convoluted
      tubule (PCT) at 1, 8, 16, and 21 days after birth. The enzyme levels in PCT of
      juxtamedullary and subcapsular nephrons were compared at 8, 16, and 21 days. A
      role of thyroid hormones in regulating the development of these enzymes was
      investigated by studying 8- and 21-day-old pups made hypothyroid by
      propylthiouracyl (PTU) treatment, as well as 21-day hyperthyroid rats. PTU
      treatment had no effect on enzyme activities on day 8. In contrast, the activity
      of all mitochondrial enzymes, except acetoacetyl-CoA thiolase, was significantly
      decreased in 21-day-old hypothyroid pups. In hypothyroid animals, the normal
      development of 3-ketoacid-CoA transferase, citrate synthase, and carnitine
      acetyltransferase could be restored after treatment by triiodothyronine (T3). In
      addition, one single injection of T3 to 8-day-old control pups induced a
      precocious rise in the activity of 3-ketoacid-CoA transferase, citrate synthase,
      and carnitine acetyltransferase in juxtamedullary PCT and in the activity of
      citrate synthase and carnitine acetyltransferase in subcapsular PCT. Altogether,
      these results point out the importance of the postnatal physiological rise in T3
      in triggering the development of some mitochondrial oxidative enzymes in the PCT.

PMID- 7733321
TI  - Enhanced transcription of metallothionein genes in rat kidney: effect of
      uninephrectomy and compensatory renal growth.
AB  - Metallothioneins (MTs) have been implicated in the intracellular regulation of
      essential metals in eukaryotic cells, and increased expression of MT genes has
      been demonstrated during the growth and proliferation of cells. To explore the
      expression of MT in somatic cells undergoing growth (hypertrophy) in the kidney
      in situ, we measured the rates of transcription of the genes for MT-1 and MT-2,
      measured the levels of mRNA for MT-1 and MT-2, and measured the concentration of
      MT-1 and MT-2 protein in samples of renal (and hepatic) tissue from
      uninephrectomized (NPX) and sham-operated (SO) rats 15 days after surgery. The
      rates of transcription of the genes for MT-1 and MT-2 were found to be enhanced
      significantly in the remnant renal mass, particularly in the cortex and outer
      stripe of the outer medulla, and in the liver, after uninephrectomy and after 15
      days allowing for compensatory renal growth. Increased accumulation of mRNA for
      MT-1 and MT-2 also occurred in the cortex and outer stripe of the outer medulla
      of the remnant kidney and in the liver in the NPX rats. Increased concentration
      of MT-1 and MT-2 protein (measured by radioimmunoassay), at the level of the
      whole kidney, renal cortex, and liver, was another feature detected in rats after
      uninephrectomy and 15 days of compensatory renal growth. These findings indicate
      that compensatory renal growth in response to uninephrectomy is associated with
      the induction of the expression of MT genes in the renal cortex and outer stripe
      of the outer medulla, as well as in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733322
TI  - Renal localization and actions of adrenomedullin: a natriuretic peptide.
AB  - Adrenomedullin (ADM) is a newly described 52-amino acid peptide originally
      isolated from extracts of human pheochromocytoma and, more recently, detected in
      human plasma. Based on the report that ADM mRNA and immunoreactivity are present
      in the kidney, the current study was designed to determine the renal distribution
      of ADM by immunohistochemistry and the renal biological actions of ADM. In the
      immunohistochemical studies, the present investigation demonstrated the
      localization of ADM in glomeruli, cortical distal tubules, and medullary
      collecting duct cells of the normal canine kidney. In the in vivo studies, ADM
      was administered (0.25 ng.kg-1.min-1 in group I and 1, 5, and 25 ng.kg-1.min-1 in
      group II) intrarenally in normal mongrel dogs with the contralateral kidney
      receiving only saline vehicle. Intrarenal infusion of ADM resulted in a marked
      diuretic and natriuretic response, whereas the contralateral kidney showed no
      renal effects. These significant natriuresis and diuresis in the ADM kidney were
      associated with increases in glomerular filtration rate and fractional sodium
      excretion and with a decrease in distal tubular sodium reabsorption. Intrarenal
      infusion of ADM also caused an increase in mean arterial blood pressure and a
      decrease in heart rate. Plasma concentrations of atrial natriuretic peptide,
      renin activity, aldosterone, and guanosine 3',5'-cyclic monophosphate were not
      changed during the infusion of ADM. The current study demonstrates that ADM is
      present in renal glomerular and tubular cells and is a potent natriuretic peptide
      that may play an important role in the regulation of sodium excretion.

PMID- 7733323
TI  - Regulation of transcription by the rat EGF gene promoter in normal and ischemic
      murine kidney cells.
AB  - Epidermal growth factor (EGF) is a small polypeptide belonging to a class of
      molecules that can mediate cell growth, differentiation, and acute phase
      responses. EGF mRNA is transcribed primarily in cells of the salivary gland and
      the kidney. We have found that the tissue and cellular specificities of EGF gene
      expression are controlled by a promoter region located upstream from the start of
      mRNA transcription. In a variety of experimentally induced forms of acute renal
      failure, the mRNA and protein levels for kidney EGF fall markedly and remain low
      for a prolonged period. This decrease was determined by nuclear runoff
      transcription to be a consequence of diminished transcription of the EGF gene
      rather than increased instability of the mRNA. Using transgenic mice, we found
      the effect of renal ischemia on EGF mRNA transcription to be a result of a
      disease-mediated interruption of the function of this upstream promoter region,
      presumably from alterations in the activity of one or more cellular trans-acting
      factors.

PMID- 7733324
TI  - Modulation of intracellular Ca2+ by glucose in MDCK cells: role of endoplasmic
      reticulum Ca(2+)-ATPase.
AB  - Intracellular free calcium ([Ca2+]i) has multiple functional roles in renal
      epithelia, including mediating ligand- and volume-activated K+ and Cl- channels,
      modulating the permeability of apical membrane to Na+, and regulating
      tubuloglomerular feedback. We investigated glucose effects on intracellular pH
      (pHi) and [Ca2+]i in Madin-Darby canine kidney (MDCK) cells using fluorescent
      probes, SNARF-1 and fura 2, respectively. The addition of glucose decreased both
      pHi and [Ca2+]i in a dose-dependent fashion. Thapsigargin (TG) and cyclopiazonic
      acid (CPA), well-known endoplasmic reticulum (ER) Ca(2+)-adenosinetriphosphatase
      (Ca(2+)-ATPase) inhibitors, abolished the glucose-induced [Ca2+]i decrease.
      Without glucose, 1 microM TG induced a sustained elevation in [Ca2+]i, which
      increased further with glucose addition, whereas 15 microM CPA induced a
      transient increase in [Ca2+]i that was not affected by further addition of
      glucose. The sustained elevation in [Ca2+]i induced by TG was dependent on
      extracellular Ca2+. TG-induced [Ca2+]i increase was modulated by glucose, i.e.,
      at higher glucose concentrations, TG induced a larger and more rapid rise in
      [Ca2+]i. We conclude that glucose has dual effects on [Ca2+]i regulation. Glucose
      alone reduces [Ca2+]i by activating ER-type Ca(2+)-ATPase, since this phenomenon
      is TG and CPA sensitive. In the presence of TG, glucose increases [Ca2+]i
      probably by increasing Ca2+ entry. Our data suggest a model in which TG activates
      capacitative Ca2+ entry by depletion of the ER Ca2+ pool. Glucose increases TG
      induced [Ca2+]i elevation by further enhancing capacitative Ca2+ entry.

PMID- 7733325
TI  - Convective uphill transport of NaCl from ascending thin limb of loop of Henle.
AB  - In this paper we describe a mathematical model of the renal inner medulla based
      on a previously proposed model [A.S. Wexler, R.E. Kalaba, and D.J. Marsh. Am. J.
      Physiol. 260 (Renal Fluid Electrolyte Physiol. 29): F368-F383, 1991] in which in
      the inner medullary ascending thin limb of Henle's loop (ATL) and collecting duct
      (CD) exchange with a local capillary node with the reabsorbed water and solutes
      flowing radially toward a central vascular bundle. Our model differs in that
      ascending and descending vasa recta and surrounding interstitial space are
      replaced by a central core. Our analysis of the coupled ATL-CD system shows that
      it is theoretically capable of transporting NaCl out of the ATL into the central
      vascular space (approximated by the central core) against a concentration
      gradient, which in the absence of radial diffusion can be arbitrarily large. By
      numerical solution of the model with the radial diffusion coefficient (D(r)) for
      NaCl of 0, we find that the ATL can be more than 100 mosmol/l hypotonic with
      respect to the core. We also find that with restricted diffusion the osmolality
      of the CD at the papilla is significantly greater than that of the loop of Henle.
      As D(r) approaches the diffusion coefficient of NaCl in free solution, the
      osmolality of the loop increases and that of the CD decreases. Thus, overall,
      contrary to intuitive expectations, the radial separation and uphill transport of
      NaCl do not give any significant increase in loop concentration, which depends
      primarily on the quantity of urea reabsorbed from the CD.

PMID- 7733326
TI  - Comparison of central core and radially separated models of renal inner medulla.
AB  - In this paper we describe the effect of partitioning exchange of ascending thin
      limb (ATL) and collecting duct (CD) between a central vascular space (CORE) and a
      radially separated capillary node (NODE) in a mathematical model of the
      concentrating mechanism of the renal inner medulla. A detailed description of the
      model has been provided [J. L. Stephenson, J. F. Jen, H. Wang, and R. P.
      Tewarson. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F680-F692,
      1995]. We define a partition coefficient theta, which denotes the fractional
      exchange of CD and ATL with the NODE. Thus with theta = 0 we have a central core
      model, in which the ATL and CD exchange with the CORE only, and with theta = 1 we
      have a totally radially separated model, in which the ATL and CD exchange with
      the NODE only. Decreasing the partition coefficient from 1 to 0 effects a
      continuous transition from a totally radially separated model to a central core
      model. As this transition progresses with increasing exchange with the CORE, the
      osmolalities in all structures become nearly the same at the papilla, and the
      ability to transport salt uphill is lost. This is true even with no radial
      diffusion. However, radial diffusion and direct exchange with the CORE act
      synergistically in decreasing osmolality differences at the papilla and the
      capacity for convective uphill transport. These are lost in a more or less
      parallel way. There is, however, no significant concomitant change in
      concentrating ability. These results indicate that models with radial mixing of
      the interstitial vascular space are probably reasonably good approximations for
      the inner medulla.

PMID- 7733327
TI  - Effect of vasa recta flow on concentrating ability of models of renal inner
      medulla.
AB  - In this study we extend the analysis of the preceding two studies [J. L.
      Stephenson, J. F. Jen, H. Wang, and R. P. Tewarson. Am. J. Physiol. 268 (Renal
      Fluid Electrolyte Physiol. 37): F698-F709, 1995; and J. F. Jen, H. Wang, R. P.
      Tewarson, and J. L. Stephenson. Am. J. Physiol. 268 (Renal Fluid Electrolyte
      Physiol. 37): F000-F000, 1995] to a model that includes vasa recta. Distribution
      of nephron and vasa recta lengths is represented by shunting from descending to
      ascending flow. It is found that the effect of radial separation of structures on
      concentrating ability is closely linked to vasa recta flow. With minimal or no
      vasa recta flow the extent of radial mixing has little effect on concentrating
      ability. As vasa recta flow increases, concentrating ability is decreased by
      radial mixing. Convective uphill transport of NaCl is again observed, but
      concentrating ability appears to depend primarily on urea delivery to the inner
      medulla from the collecting duct rather than on the mechanism of salt transport
      out of thin ascending limb. Central core models give an upper bound on
      concentrating ability but do not attain the maximum urine osmolality of the rat
      with experimental values of tubular permeabilities.

PMID- 7733328
TI  - Role of glucocorticoids in the maturation of renal cortical Na+/H+ exchanger
      activity during fetal life in sheep.
AB  - We have studied the role of glucocorticoids in inducing the maturation in
      activity of the proximal tubule Na+/H+ exchanger that follows birth. Renal
      cortical microvillus membrane vesicles were prepared from 132-day gestation sheep
      fetuses (n = 8) that had received intraperitoneal cortisol (13 micrograms.kg-1.h
      1) for the previous 48 h. Membrane vesicles were also obtained from sham-operated
      twin controls (n = 8). Amiloride-sensitive uptake of 22Na+ by these vesicles was
      measured, and Woolf-Augustinsson-Hofstee plots were used to determine the
      Michaelis constant (Km) and maximal velocity (Vmax). There was no significant
      difference in Km; however, the Vmax was 61% higher in cortisol-treated fetuses.
      Posttreatment circulating cortisol levels were significantly higher in the
      treated fetuses. Total RNA was collected from renal cortex of the eight pairs of
      twins when killed. Renal cortex Na+/H+ exchanger 3 (NHE3) mRNA levels were
      approximately fourfold higher in cortisol-treated than in control fetuses.
      Although proximal tubule Na+/H+ exchanger activity and renal cortex NHE3 mRNA
      levels increased significantly in cortisol-treated fetuses, cortisol infusion did
      not stimulate renal sodium reabsorption in the fetus but rather produced a
      natriuresis. These results demonstrate that glucocorticoids can induce an
      increase in both Na+/H+ exchanger activity and NHE3 mRNA levels during the last
      trimester of gestation in sheep. However, these changes are not associated with
      an increased ability of the fetal kidney to reabsorb sodium.

PMID- 7733329
TI  - Clearance of endogenous lithium in humans: altered dietary salt intake and
      comparison with exogenous lithium clearance.
AB  - We compared endogenous with exogenous lithium clearance (CLi) and studied the
      effects of dietary salt intake on endogenous CLi in healthy volunteers. Lithium
      was detectable within a narrow fourfold range in serum and in urine in all 25
      subjects studied [serum (n = 25), mean 0.27 +/- 0.02 mumol/l, range 0.13-0.55
      mumol/l; urine (n = 20), range 1.49-7.32, mean 4.09 +/- 0.36 mumol/24 h]. Mean
      clearance and fractional excretion of endogenous lithium were lower (15.2 +/- 2.0
      ml/min and 16.4 +/- 2.1%, respectively) compared with results obtained using the
      exogenous CLi technique (25.5 +/- 1.7 ml/min and 27.9 +/- 2.1%; P < 0.01 and P <
      0.05, respectively; n = 17). In a separate group of six normal subjects, absolute
      (8.7 +/- 2.9 vs. 20.7 +/- 3.8 ml/min) and fractional excretion of lithium (8.3 +/
      2.9 vs. 18.0 +/- 5.1%) were significantly lower on 5 days of low (31 +/- 10
      mmol/day) vs. high sodium intake (357 +/- 78 mmol/day; P < 0.05). Use of
      endogenous CLi precludes the need for lithium tablets. This could be a particular
      advantage in population studies and permits serial measurement of CLi on
      different days. Our results show that it is important to take dietary sodium
      intake into account in studies of endogenous CLi. Lower values for endogenous
      compared with exogenous CLi could reflect differences in renal handling depending
      on the plasma lithium concentration. This clearly requires further study.

PMID- 7733330
TI  - Chloride transport in the rat S1 proximal tubule.
AB  - In vivo microperfusion was used to elucidate the modes and regulation of the
      powerful chloride transport system resident in the rat early (S1) proximal
      convoluted tubule (PCT). From a complete, glomerular ultrafiltrate-like
      perfusate, omission of organic solutes reduced chloride absorption by 93 peq.mm
      1.min-1 (302 +/- 10 to 209 +/- 24, P < 0.001). From a high-chloride perfusate (a
      relatively pure NaCl solution devoid of bicarbonate and organic solutes), luminal
      addition of the active transport inhibitor cyanide reduced chloride absorption by
      153 peq.mm-1.min-1 (632 +/- 17 to 479 +/- 9, P < 0.001). Active transport was
      also estimated directly as 121 +/- 4 peq.mm-1.min-1 using a solution in which
      sodium isethionate isosmotically replaced bicarbonate and organic solutes,
      preventing development of a chloride gradient. Intravenous angiotensin II caused
      a stimulation of chloride absorption from a high-chloride perfusate by 55 peq.mm
      1.min-1 (632 +/- 17 to 687 +/- 14, P < 0.05), which was partially cyanide
      sensitive (510 +/- 6 peq.mm-1.min-1). In conclusion, the components of the normal
      S1 PCT chloride reabsorption (approximately 300 peq.mm-1.min-1) from the
      glomerular ultrafiltrate consist of the following: active transport (40-50%),
      which can be regulated by angiotensin II; sodium-coupled organic solute transport
      (30%); and passive, chloride concentration gradient-driven transport (20-25%).

PMID- 7733331
TI  - Error propagation in the estimation of glomerular pressure from macromolecule
      sieving data.
AB  - The theoretical effects of the glomerular transmural hydraulic pressure
      difference (delta P) on the sieving coefficients (theta i) of macromolecules of
      varying size have led to a number of attempts to use sieving curves to estimate
      delta P noninvasively, with inconsistent results. The objective of this study was
      to determine the extent to which experimental errors and imperfections in the
      theoretical models limit the ability to obtain reliable estimates of delta P
      using this method. Our approach was to generate many sets of synthetic
      "experimental data" using computer simulations of glomerular sieving and to
      compute values of delta P by fitting models to those data in the presence of
      various types and magnitudes of errors. Unbiased experimental errors were
      simulated by adding random amounts to individual values of theta i, and
      systematic errors were investigated by using a model based on one type of pore
      size distribution to fit "data" generated using a model of a different type. We
      found that with random errors in theta i only, the estimate of delta P was
      accurate to within +/- 4 mmHg nearly all of the time, provided that the standard
      deviation, sigma i, was < or = 5% of theta i. When there were also systematic
      errors arising from the use of an "incorrect" form of pore-size distribution, a
      useful predictor of success was the probability P that the residuals, the
      differences between the measured and predicted sieving coefficients, were
      randomly distributed. A value of P > 0.2, as calculated from the algebraic signs
      of the residuals, indicated a high likelihood that the pressure estimate was
      accurate, provided that the random errors were sufficiently small. When P > 0.2,
      the fitted value of delta P was within +/- 4 mmHg of the true value in about 90%,
      80%, and 70% of the cases examined when sigma i was < or = 2%, 5%, or 10% of
      theta i, respectively. An analysis of published data from a number of
      experimental studies indicated, however, that the favorable conditions of small
      sigma i and large P are extremely difficult to achieve, making it unlikely that
      an accurate group-mean value of delta P will be estimated from any given set of
      sieving data. Significant experimental and theoretical advances will be needed to
      make this a reliable method for estimating glomerular pressure.

PMID- 7733332
TI  - Kinetics of monocyte 1 alpha-hydroxylase in renal failure.
AB  - In chronic uremia, the requirement of supraphysiological doses of serum 25
      hydroxyvitamin D3 [25(OH)D3] for the normalization of 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] levels has been attributed to impaired substrate availability to
      renal 1 alpha-hydroxylase. Because serum 1,25(OH)2D3 can also be corrected by
      25(OH)D3 supplementation in bilaterally nephrectomized patients, we examined the
      role of substrate availability on 1,25(OH)2D3 production by peripheral blood
      monocytes (PBM). In hemodialysis patients (HP), 25(OH)D3 uptake was 50% lower
      than normal, and the maximal velocity (Vmax) and apparent Michaelis constant (Km)
      for 25(OH)D3 of 1 alpha-hydroxylase were 2.7- and 4-fold above normal,
      respectively. When serum 1,25(OH)2D3 of HP was corrected by intravenous
      1,25(OH)2D3, 25(OH)D3 uptake, Km, and Vmax returned to normal values. The effect
      of 25(OH)D3 supplementation was also examined. In normal adults, 25(OH)D3
      administration had no effect on serum 1,25(OH)2D3 levels nor on the Km or the
      Vmax of PBM 1 alpha-hydroxylase but caused a 11-fold increase in serum 24R,25
      dihydroxyvitamin D3[24R, 25(OH)2D3]. In HP, 25(OH)D3 therapy raised serum
      1,25(OH)2D3 and reduced the Km and Vmax of PBM 1 alpha-hydroxylase, which
      correlated negatively with serum 1,25(OH)2D3. However, serum 24R,25(OH)2D3 only
      increased slightly above basal. These results demonstrate that, in HP, 1)
      impaired uptake of 25(OH)D3 and low affinity for substrate determine the need for
      high 25(OH)D3 levels to normalize serum 1,25(OH)2D3, despite higher enzymatic
      activity; 2) 1,25(OH)2D3 deficiency plays a role in enhanced 1,25(OH)2D3
      synthesis and impaired access of 25(OH)D3 to PBM 1 alpha hydroxylase; and 3)
      abnormal 25(OH)D3 delivery also affects 24-hydroxylation.

PMID- 7733333
TI  - Effect of peptide YY on human renal function.
AB  - Peptide YY (PYY) is released from the intestine into the circulation in response
      to ingestion of food. As PYY/neuropeptide Y (NPY) receptors have recently been
      identified in the human kidney, we examined the effect of PYY on human renal
      function. Male subjects (6 per group) received control infusate or PYY at 0.4 or
      1.2 pmol.kg-1.min-1 intravenously for 90 min with control periods before and
      after. Infusion of PYY at the lower dose reproduced normal postprandial plasma
      concentrations and caused significant decreases in glomerular filtration rate
      (10% reduction), plasma renin activity (30% reduction), and aldosterone levels
      while increasing sodium excretion by approximately 30% (all P < 0.01). Infusion
      of PYY at the higher dose, which reproduced plasma levels seen during a diarrheal
      illness, resulted in similar changes in renal function and also reduced renal
      plasma flow by approximately 10% (P < 0.05). Therefore, PYY may be an important
      mediator of the normal postprandial natriuretic response, and PYY agonists could
      provide a novel approach to the treatment of patients with sodium overload.

PMID- 7733334
TI  - Two proximal CArG elements regulate SM alpha-actin promoter, a genetic marker of
      activated phenotype of mesangial cells.
AB  - Mesangial cells express smooth muscle alpha-actin (SM alpha-actin) in response to
      glomerular injury in vivo, and SM alpha-actin gene expression serves as a genetic
      marker characterizing the activated phenotype of mesangial cells. We used a
      molecular genetic approach to analyze the SM alpha-actin promoter and evaluate
      transcriptional mechanisms that might direct the genetic switch of mesangial
      cells to the activated phenotype. The sequence spanning -894 to +1 of the SM
      alpha-actin promoter directed high levels of transcription that were attenuated
      in serum-restricted cells and upregulated upon treatment with serum or endothelin
      1. Deletional analysis revealed a core promoter fragment, from positions -122 to
      +1, that was necessary and sufficient for transcription. This core activity was
      modulated by upstream sequences between -670 and -122. The 122-bp core promoter
      contains two highly conserved CArG box motifs (designated CB1 and CB2), and
      introduction of deletion mutations of either CB1 or CB2 reduced transcription in
      mesangial cells to near basal levels. Further analysis revealed that CB1 and CB2
      acted synergistically when subcloned upstream of a heterologous, minimal
      thymidine kinase promoter. CB2 alone was sufficient to confer serum inducibility
      to a heterologous promoter, but both CB2 and CB1 were required for maximal levels
      of serum-induced transcription. Collectively, these results demonstrate that CB1
      and CB2 cooperate to mediate serum-induced activation of the SM alpha-actin
      promoter in mesangial cells.

PMID- 7733335
TI  - Effect of barium on potassium diffusion across the proximal convoluted tubule of
      the anesthetized rat.
AB  - The role of diffusion in transepithelial potassium flux and the importance of
      potassium channels in the luminal cell membrane to this process were examined by
      applying a luminal microperfusion technique to surface tubules in kidneys of
      anesthetized rats. Potassium concentration gradients were applied by altering the
      concentration of KCl in perfusates. To some perfusates, 2 mmol/l BaCl2 was added
      to block potassium channels in the luminal cell membrane. The mean applied
      potassium concentration gradient was highly predictive of net potassium transport
      in the absence of any change in fluid reabsorption, with an apparent potassium
      permeability of 22 x 10(-5) cm/s. Thus potassium transport in the proximal tubule
      may have an important diffusive component. Luminal barium significantly reduced
      the concentration of potassium in collected fluid under conditions of net
      potassium secretion, although a substantial barium-insensitive potassium
      permeability was also observed. However, the site of action of luminally applied
      barium is uncertain in proximal tubule, since barium was reabsorbed by the tubule
      at a rate of 13.6 pmol.mm-1.min-1. We conclude that diffusion is a significant
      driving force for potassium reabsorption in proximal tubule and that most
      diffusive potassium transport occurs via a barium-insensitive route, possibly the
      paracellular pathway.

PMID- 7733336
TI  - Parathyroid hormone action on phosphate transporter mRNA and protein in rat renal
      proximal tubules.
AB  - The inhibitory action of parathyroid hormone (PTH) on Pi reabsorption in the
      renal proximal tubule is accompanied by a specific decrease in Na-Pi cotransport
      at the apical brush-border membrane (BBM). It is not known whether this decrease
      represents decreased activity of Na-Pi cotransporters already present in the BBM
      or whether the number of cotransporters is decreased. The present study of the
      molecular mechanism of PTH action made use of a specific cDNA probe and antiserum
      to a rat renal Na-Pi cotransporter (NaPi-2). Three groups of rats were used:
      intact controls, chronically parathyroidectomized (PTX), and PTX rats treated
      acutely (2 h) with bovine PTH-(1--34). Na-Pi cotransport by isolated renal BBM
      vesicles was increased to 1,315 +/- 44 in PTX rats, compared with 721 +/- 94
      pmol.mg-1.10 s-1 in controls (P < 0.002), and was returned to control levels by
      PTH. Western blots of these BBM showed that PTX caused a 2.8-fold increase in
      NaPi-2 protein content, which was reduced to control levels by PTH.
      Immunohistochemistry of perfusion-fixed kidneys showed NaPi-2-specific
      immunofluorescence exclusively in apical BBM of proximal tubules. Expression of
      NaPi-2 protein at these sites was increased in PTX rats and decreased after PTH
      treatment. Northern analysis of total RNA showed that the abundance of NaPi-2
      specific mRNA was not changed by PTX but there was a small decrease in response
      to PTH. The data indicate that PTH regulation of renal Na-Pi cotransport is
      determined by changes in expression of NaPi-2 protein in the renal BBM.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7733337
TI  - A novel 5-HT1-like receptor subtype mediates cAMP synthesis in porcine pial vein.
AB  - The 5-hydroxytryptamine (5-HT) receptor subtype mediating 5-HT inhibition of
      spontaneous rhythmic contractions (SRC) in the porcine pial vein was
      characterized. Results from pharmacological studies using in vitro tissue bath
      techniques indicated that the inhibitory effects of 5-HT on SRC were
      qualitatively and quantitatively mimicked by 5-HT1-like agonists 5
      methoxytryptamine (5-MT) and 5-carboxamidotryptamine (5-CT). 5-HT-, 5-MT-, and 5
      CT-induced inhibitions of SRC were attenuated in a concentration-dependent manner
      by methysergide, which yielded similar pA2 values against these three agonists,
      suggesting that 5-HT, 5-MT, and 5-CT act on the same 5-HT1-like receptors. 5-MT
      inhibition of SRC was not affected by blocking 5-HT2 (with ketanserin and
      spiperone), 5-HT3 (with MDL-72222 and ICS-205-930), or 5-HT4 (with ICS-205-930)
      receptors. Neither was 5-MT inhibition of SRC affected by blocking 5-HT1A (with
      propranolol and spiperone), 5-HT1B (with propranolol), or 5-HT1C (with
      ketanserin) receptors. Furthermore, 5-HT and 5-MT inhibitions of SRC were
      enhanced by cilostazol [a selective adenosine 3',5'-cyclic monophosphate (cAMP)
      phosphodiesterase inhibitor] and were diminished by KT-5720 (a cAMP-dependent
      protein kinase inhibitor) but were not affected by M&B-22948 [a selective
      guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor] or KT
      5823 (a cGMP-dependent protein kinase inhibitor). Biochemical studies further
      demonstrated that 5-HT inhibition of SRC in porcine pial veins was accompanied by
      an increase in cAMP, but not cGMP, synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733338
TI  - ATP-MgCl2 restores depressed endothelial cell function after hemorrhagic shock
      and resuscitation.
AB  - Although ATP-MgCl2 produces beneficial effects following various adverse
      circulatory conditions, it remains unknown whether this agent restores the
      depressed endothelial cell function [i.e., the reduced release of endothelium
      derived nitric oxide (EDNO) and endothelium-derived contracting factors (EDCF)]
      in a model of trauma-hemorrhage and resuscitation. To determine this, rats
      underwent laparotomy (i.e., trauma induced), were bled to and maintained at a
      mean arterial pressure of 40 mmHg until 40% of shed blood volume was returned in
      the form of Ringer lactate (RL). The animals were then resuscitated with four
      times the volume of maximal bleedout with RL, following which ATP-MgCl2 (50
      mumol/kg body wt) or saline was administered. At 1.5 h postresuscitation, the
      aorta and superior mesenteric artery (SMA) were isolated, and dose-responses for
      acetylcholine (ACh, an endothelium-dependent vasodilator, via EDNO) and
      nitroglycerin (an endothelium-independent vasodilator) were determined. In
      addition, hypoxia-induced contraction, a process mediated by EDCF, was assessed.
      The results indicate that the decreased endothelium-dependent relaxation after
      hemorrhage (sham 94 +/- 3 and 97 +/- 3% vs. hemorrhage 64 +/- 5 and 57 +/- 11% at
      10-5 M ACh in aorta and SMA, respectively, P < 0.05) was restored with ATP-MgCl2
      treatment. In contrast, there was no significant difference in nitroglycerin
      induced relaxation. Moreover, the decreased hypoxia-induced aortic contraction
      after hemorrhage (sham 221 +/- 26 mg/ring vs. hemorrhage 124 +/- 22 mg/ring, P <
      0.05) was attenuated by administration of ATP-MgCl2.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7733339
TI  - Technical aspects of evaluating brachial artery vasodilatation using high
      frequency ultrasound.
AB  - Flow-mediated brachial artery vasoactivity has been recently proposed as a
      noninvasive means for assessing endothelial function. To better characterize this
      technique, we measured brachial artery diameter and flow using 7.5-MHz ultrasound
      following 1, 3, and 5 min of upper arm blood pressure cuff occlusion in 19 normal
      volunteers and 13 patients with coronary artery disease (CAD). Although similar
      flow increases were observed with each protocol, statistically significant
      vasodilatation (12.6 +/- 5.7%) was observed in the normals only after 5 min of
      occlusion. With the use of this protocol, postocclusion blood flow increased 528
      +/- 271 and 481 +/- 247% in the normals and CAD patients, respectively (P = NS).
      More vasodilatation was observed in the normals compared with the CAD patients
      (11.3 +/- 5.4 vs. 1.6 +/- 5.2%, P < 0.001). Interestingly, vasodilatation
      persisted for 20 min despite return of blood flow to baseline in 2 min. With the
      use of lower arm occlusion, arterial diameter was found to decrease 4.4 +/- 3.9%
      in response to a 85 +/- 7% decrease in flow. We conclude that 1) longer brachial
      artery occlusion results in more vasodilatation despite similar hyperemic
      responses, 2) vasodilatation persists substantially beyond hyperemia, and 3) CAD
      patients have impaired flow-mediated vasodilatation using this noninvasive
      technique.

PMID- 7733340
TI  - Synergistic regulation of ANF in isolated rat hearts.
AB  - The interaction between cardiac sympathetic stimulation of atrial natriuretic
      factors (ANF) release and left atrial stretch was examined in groups (n = 5 or 6)
      of isolated, perfused (10 ml/min), paced rat hearts. Left atrial stretch,
      produced by an increase in atrial pressure of 1.1 +/- 0.2 mmHg over 8 min,
      transiently (4 min) increased ANF release by 46 +/- 4% over baseline (220 pg/ml
      buffer; P < 0.05). Infusion of 1 microM norepinephrine (NE) over 28 min caused a
      sustained increase in ANF release of 76 +/- 10% (P < 0.05). Atrial stretch plus
      NE caused additive effects on ANF release during stretch but 2.4 times the
      additive effects after stretch (P < 0.05). To examine whether resting tension
      modulates the ANF response to sympathetic stimulation, the left atrium was
      stretched throughout the experiment by increasing the atrial pressure by 1-1.5
      mmHg. Infusion of 1 microM NE over 28 min increased ANF release by 216 +/- 46% (P
      < 0.01) in the prestretched heart, compared with a calculated summed increase of
      85% due to NE alone plus prestretch alone. Infusion of 0.5 microM veratridine,
      known to stimulate ANF via mechanical effects on the heart, increased ANF release
      by 88 +/- 3% (P < 0.01). Scorpion venom, known to dose dependently stimulate ANF
      secretion via activation of neuronal sodium channels, elicits a negligible
      increase in ANF release at the threshold concentration of 0.1 microM. The
      combined infusion of 0.5 microM veratridine plus 0.1 microM venom increased ANF
      release by 239 +/- 53% (n = 6, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733341
TI  - Mitochondrial lipid peroxidation and superoxide dismutase in rat hypertensive
      target organs.
AB  - Mitochondrial respiratory chains leak a large amount of superoxide anion
      radicals, which chain react with membrane phospholipid to develop lipid
      peroxidation. Manganese superoxide dismutase (MnSOD) is then inducible and
      catalyzes superoxide detoxification within mitochondria. We examined
      mitochondrial thiobarbituric acid-reactive substance, an end product of lipid
      peroxidation, and MnSOD concentration in hypertensive target organs of
      spontaneously hypertensive and deoxycorticosterone acetate salts-induced
      hypertensive rats. Normotensive rats showed significant increases in
      thiobarbituric acid-reactive substance and MnSOD in the brain as they matured.
      Mature spontaneously hypertensive and induced hypertensive rats showed a marked
      elevation of lipid peroxidation but no increase in superoxide dismutase in the
      brain. The heart and kidney presented no significant difference of lipid
      peroxidation and superoxide dismutase among strains, ages, and treatments.
      Abnormal mitochondrial metabolism of oxygen radicals was observed selectively in
      the brain during hypertension and may contribute to mitochondrial injury and lead
      to neuronal degeneration or susceptibility to brain ischemia in mature
      hypertensive rats.

PMID- 7733342
TI  - Sites of inhaled NO-induced vasodilation during hypoxia and U-46619 infusion in
      isolated lamb lungs.
AB  - The sites of relaxation in response to inhaled nitric oxide (NO) were
      investigated using the vascular occlusion technique in isolated blood-perfused
      lungs from 1- to 3-mo-old lambs. In one group of 10 lungs, inhaled NO (45 ppm)
      was administered during hypoxia- and U-46619-induced pulmonary vasoconstriction.
      In a second group of 5 lungs, responses to inhaled NO and infused sodium
      nitroprusside (SNP, 3 micrograms.kg-1.min-1) during U-46619-induced hypertension
      were compared. Hypoxia caused significant pulmonary vasoconstriction, with
      increases in the pressure gradients of large and small arteries and small veins,
      as defined by vascular occlusion. Inhaled NO significantly reduced the total
      pulmonary pressure gradient by 67% and relaxed both large and small arteries.
      Infusion of U-46619 caused significant increases in all segmental pressure
      gradients. While inhaled NO was effective in relaxing the large and small
      arteries and the small veins, it had no effect on the large veins. Infusions of
      SNP, a nitrosovasodilator thought to act like endogenous NO, caused a similar
      degree of total relaxation as NO (81 vs. 77%, respectively). However, in contrast
      to inhaled NO, SNP was effective in reducing the pressure gradient of the large
      pulmonary veins. These results suggest that rapid binding to and thus
      inactivation of inhaled NO by hemoglobin limit its efficacy as a pulmonary venous
      dilator.

PMID- 7733343
TI  - Exercise training alters aortic vascular reactivity in hypothyroid rats.
AB  - Hypothyroidism induces a number of cardiovascular adaptations in rats, including
      decreases in blood flow to high-oxidative skeletal muscle and increases in total
      peripheral resistance. Conversely, exercise training results in elevations in
      blood flow to high-oxidative skeletal muscle and decreases in vascular
      resistance. The purpose of this study was to determine whether hypothyroidism
      induces changes in the vasomotor responses of arterial vessels and whether
      exercise training modifies these responses. Rats were divided into three groups,
      sedentary euthyroid (S-Eut), sedentary hypothyroid (S-Hypo), and exercise-trained
      hypothyroid (ET-Hypo). Responses to vasoactive compounds were examined in vitro
      using abdominal aortic rings. Maximal isometric contractile tension (g/mm2)
      evoked by KCl and norepinephrine (NE) were not different among groups. However,
      sensitivity to KCl [agonist concentration producing 50% of maximal
      vasoconstrictor response (EC50; in mM): S-Eut, 21.1 +/- 1.1; S-Hypo, 35.7 +/-
      2.7; ET-Hypo, 43.8 +/- 2.0] and to NE [EC50 (in M): S-Eut, 4.0 x 10(-8) +/- 2.3 x
      10(-8); S-Hypo, 8.3 x 10(-8) +/- 3.4 x 10(-8); ET-Hypo, 3.6 x 10(-7) +/- 1.1 x
      10(-7)] was different among groups, and in the order S-Eut > S-Hypo > ET-Hypo.
      Maximal vasodilator responses induced by acetylcholine (10(-7) M NE
      preconstriction) were lower in rings from S-Hypo animals than those from S-Eut
      and ET-Hypo rats. Dilatory responses induced by sodium nitroprusside (SNP) with
      the same NE preconstriction were not different among groups. However, with a 10(
      4) M NE preconstriction, maximal dilatory responses induced by SNP were lower in
      vessels from hypothyroid animals. Dilatory responses to forskolin (10(-4) M NE
      preconstriction) were not different among groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7733344
TI  - Role of nitric oxide and cAMP in prostaglandin-induced pial arterial
      vasodilation.
AB  - The present study was designed to investigate the role of nitric oxide (NO),
      guanosine 3',5'-cyclic monophosphate (cGMP), and adenosine 3',5'-cyclic
      monophosphate (cAMP) in the vasodilator response to prostaglandin (PG)I2 and PGE2
      in newborn pigs equipped with a closed cranial window. PGI2 (1-100 ng/ml)
      produced pial arterial dilation that was blunted by nitro-L-arginine (L-NNA, 10(
      6) M), an NO synthase inhibitor (9 +/- 1 vs. 2 +/- 1%, 21 +/- 1 vs. 5 +/- 3% for
      1 and 100 ng/ml PGI2 respectively, n = 6; means +/- SE). PGI2-induced
      vasodilation was associated with increased cortical periarachnoid cerebrospinal
      fluid (CSF) cGMP, and these changes in cGMP were blocked by L-NNA (386 +/- 8 and
      1,054 +/- 30 fmol/ml vs. 266 +/- 6 and 274 +/- 4 fmol/ml for control and PGI2 100
      ng/ml before and after L-NNA respectively, n = 6). In contrast, PGI2-associated
      changes in CSF cAMP were unchanged by L-NNA (1,021 +/- 25 and 2,703 +/- 129
      fmol/ml vs. 980 +/- 23 and 2,636 +/- 193 fmol/ml for control, PGI2 100 ng/ml
      before and after L-NNA, respectively, n = 6). PGE2 elicited similar changes in
      pial artery diameter and cyclic nucleotides; vasodilation and changes in CSF cGMP
      also being similarly inhibited by L-NNA. After L-NNA, topical administration of
      the NO donor sodium nitroprusside (SNP, 10(-9) M) increased pial artery diameter
      up to the resting level before L-NNA and partially restored the vasodilation
      elicited by PGI2 and PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733345
TI  - Effects of age on intrinsic heart rate, heart rate variability, and AV conduction
      in healthy humans.
AB  - Heart rate, heart rate variability, and atrioventricular (AV) conduction were
      studied in 20 young (30 +/- 5 yr) and 19 older (69 +/- 7 yr) healthy men and
      women before and after single and double autonomic blockade (randomized order:
      atropine, 0.04 mg/kg i.v.; propranolol, 0.2 mg/kg i.v.). Basal R-R intervals did
      not differ, but older age increased P-R intervals (177 +/- 24 vs. 149 +/- 17 ms,
      P < 0.001) and decreased SD of R-R (43 +/- 17 vs. 70 +/- 18 ms, P = 0.001) and
      heart rate spectral content (area under the power vs. frequency curve from 0.04
      to 0.32 Hz: 3.01 +/- 2.1 vs. 7.82 +/- 4.8 beats/min2, P < 0.009), as well as
      postural responses (R-R decreases of 107 +/- 80 vs. 250 +/- 72 ms, P < 0.002).
      Atropine decreased R-R intervals, SD of R-R, and high-frequency (0.24-0.32 Hz)
      spectral content less in elderly subjects compared with younger subjects.
      Propranolol increased R-R and P-R intervals equally in old and young and
      abolished low-frequency (0.04-0.12 Hz) increases with standing (P < 0.0008).
      After double blockade, R-R, P-R, and paced AV intervals were longer in old
      subjects. Mean values were as follows: R-R intervals, 859 +/- 176 vs. 677 +/- 106
      ms, P < 0.001; P-R intervals, 179 +/- 23 vs. 149 +/- 17 ms, P = 0.0002; paced P-R
      intervals (500 ms), 251 +/- 39 vs. 215 +/- 47 ms; and AV block cycle length, 413
      +/- 51 vs. 385 +/- 69 ms (multivariate analysis of variance, P < 0.03). After
      double autonomic blockade, heart rate variability was nearly eliminated in young
      and old (reduced > 98%, P < 0.0001). We conclude that age differences in heart
      rate variability can be explained by autonomic influences, but heart rate and AV
      conduction differences exist independently of beta-adrenergic and/or
      parasympathetic influences.

PMID- 7733346
TI  - Determinants of maximal exercise VO2 during single leg knee-extensor exercise in
      humans.
AB  - Previously, a reduction in fractional inspired O2 (FIO2) during dynamic exercise
      of the human quadriceps muscles of one leg resulted in increased muscle blood
      flow (Q) and a fall in femoral venous O2 tension (PO2) but no change in peak O2
      uptake (VO2). These data can be interpreted as reflecting an increase in muscle
      O2 diffusive capacity (DO2) in hypoxia or, alternatively, that maximum O2 uptake
      (VO2max) was not reached for these muscles when air was breathed, in which case
      the theory of diffusion limitation to VO2max is not applicable to these data.
      Therefore, the primary goal of this study was to test the hypothesis that VO2max
      would be reduced in hypoxia as a result of the decreased O2 supply and a constant
      diffusional conductance from blood to exercising muscle. To resolve this, five
      trained men were studied performing single leg incremental knee-extensor exercise
      to VO2max while breathing air (N) and again while breathing 12% O2 (H). The
      maximum work rate (WRmax) was 30-50 W greater and produced even greater
      associated maximum leg Q (N = 9.1 +/- 0.61 and H = 8.2 +/- 0.65 l/min, P < 0.05)
      and leg O2 than in previous studies. Hypoxia reduced quadriceps muscle VO2max (N
      = 1.4 +/- 0.1 and H = 1.1 +/- 0.1 l/min, P < 0.05). In the two conditions the
      relationships between 1) measured femoral venous PO2 (N = 18 +/- 0.5 and H = 13
      +/- 0.5 Torr) and VO2max and 2) calculated mean capillary PO2 (N = 37 +/- 0.4 and
      H = 28 +/- 0.8 Torr) and VO2max were each one of proportionality.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7733347
TI  - Initiation of hyperpermeability in energy-depleted coronary endothelial
      monolayers.
AB  - How the initiation of energy depletion affects macromolecule permeability of a
      barrier of coronary endothelial cells was investigated. Cultured monolayers of
      adult rat coronary endothelial cells were exposed to 5 mM KCN and 5 mM 2-deoxy-D
      glucose (2-DG). Transendothelial flux of albumin, cellular ATP content, and
      cytosolic Ca2+ concentration were monitored. Within the first minute, a merely
      partial loss (28%) of ATP reserves provoked a distinct increase (41%) in albumin
      flux. Rise of permeability was dependent on Ca2+ release from a thapsigargin- and
      ATP-sensitive endogenous store, and hyperpermeability was greatly attenuated when
      energy depletion was extremely rapid, as under sequential addition of 20 mM 2-DG
      and 5 mM KCN. Attenuation of hyperpermeability could also be achieved by use of 5
      20 mM 2,3-butanedione monoxime, an inhibitor of actin-myosin interaction. This
      finding, together with dependence on Ca2+ and availability of residual energy,
      indicates that the rapid initiation of hyperpermeability is caused by a
      contractile mechanism.

PMID- 7733348
TI  - Identification and antisense inhibition of a renin-angiotensin system in
      transgenic cardiomyocytes.
AB  - Cardiac myocytes (AT-1 cells) derived from heart tumors of mice transgenic for an
      atrial natriuretic factor promoter, SV40 large T-antigen DNA transgene,
      demonstrate properties consistent with normal cardiac myocytes but retain the
      capacity to proliferate in culture. We studied the renin-angiotensin system (RAS)
      and related growth regulation of these cells because AT-1 cells (or
      transgenically similar cells) may be useful to repair injured myocardium. This
      study reveals two separate and distinct findings: 1) AT-1 cells proliferate or
      hypertrophy in response to angiotensin II (ANG II), depending on their competence
      to proceed through the cell cycle; and 2) AT-1 cells possess components of a RAS,
      and angiotensinogen antisense experiments suggest that the RAS is functional in
      these cells. Specifically, AT-1 cells proliferate in response to ANG II in low
      serum medium but hypertrophy in response to ANG II when first treated with
      mitomycin C (at a concentration that inhibits DNA replication but is not
      cytotoxic). The ANG II-mediated proliferative and hypertrophic responses are
      inhibited by DuP 753. In addition, there is a significant increase in the protein
      to-DNA ratio of cells, which are proliferation-inhibited in the absence of ANG II
      treatment (20%, P < 0.05). DuP 753 also inhibits this hypertrophy, suggesting
      that these cells possess a functional RAS. AT-1 cells contain mRNAs for
      angiotensin-converting enzyme, renin, angiotensinogen, and the AT1 receptor as
      determined by sequence analysis of polymerase chain reaction amplification
      products. Antisense oligonucleotides complementary to the angiotensinogen mRNA
      specifically inhibit angiotensinogen mRNA accumulation and proliferation of AT-1
      cells. In summary, these cells contain a growth-regulating RAS, suggesting that
      such a system may play a significant role in left ventricular hypertrophy.

PMID- 7733350
TI  - Conductance catheter measurement of left ventricular volume: evidence for
      nonlinearity within cardiac cycle.
AB  - The conductance catheter gain factor, alpha, is usually determined by an
      independent measure of stroke volume and, as such, is assumed to be constant.
      However, nonlinearity of the conductance-volume relation has been proposed on
      theoretical grounds. The present study was designed to establish the extent of
      nonlinearity, or variability of alpha, within the cardiac cycle using magnetic
      resonance imaging (MRI) as the reference method. Pentobarbital-anesthetized
      minipigs (n = 10, 10-13 kg) were instrumented with left ventricular (LV)
      conductance and Millar catheters. Conductance catheter signals were recorded, and
      volumes were corrected for parallel conductance using a saline-dilution
      technique. Animals were then placed in a 4.7-T magnet, and first time derivative
      of LV pressure-gated transverse MRI images (5-mm slices) acquired during
      isovolumic contraction (end diastole) and relaxation (end systole). LV cavity
      volumes were then determined using a third-order polynomial model. The gain alpha
      was computed three ways: by dividing conductance stroke volume by MRI stroke
      volume (alpha SV), by dividing conductance end-diastolic volume by MRI end
      diastolic volume (alpha ED), and by dividing conductance end-systolic volume by
      MRI end-systolic volume (alpha ES). alpha SV was 0.62 +/- 0.15, with alpha ED
      (0.71 +/- 0.17) significantly lower than alpha ES (0.81 +/- 0.21; P < 0.001).
      Using alpha SV to adjust conductance gain (i.e., assuming constant gain) resulted
      in a significantly larger end-diastolic volume (25.8 +/- 4.6 ml) and smaller
      ejection fraction (46.8 +/- 7.2%) than those obtained with MRI (23.0 +/- 4.1 ml
      and 53.1 +/- 7.3%, respectively; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733349
TI  - Disruption of cGMP production in pulmonary arteries isolated from fetal lambs
      with pulmonary hypertension.
AB  - Ligation of the ductus arteriosus of the fetal sheep produces severe pulmonary
      hypertension at birth. Standard tissue bath techniques were used to study third-
      and fourth-generation pulmonary arteries and veins isolated from fetal sheep with
      pulmonary hypertension created by ligation of the ductus arteriosus 11-12 days
      before birth as well as from age-matched control sheep. Vessels pretreated with
      indomethacin and propranolol were submaximally preconstricted with norepinephrine
      before exposure to A-23187 (10(-8) to 3 x 10(-7) M), sodium nitroprusside (SNP;
      10(-9) to 10(-5) M), and nitric oxide (NO) gas (1-973 ppm). Pulmonary veins in
      both control and ligated animals relaxed similarly and completely to A-23187,
      SNP, and NO. Control pulmonary arteries relaxed by 16 +/- 2% to A-23187 and
      relaxed completely to SNP and NO, with concentration-response curves shifted
      rightward of those observed in pulmonary veins. Pulmonary arteries from ligated
      animals did not relax at all to A-23187. SNP relaxations in ligated arteries were
      shifted rightward of control. Ligated arteries relaxed by only 11 +/- 5% to the
      highest dose of NO. However, control and ligated pulmonary arteries relaxed
      similarly to 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP; 10(-5) to
      10(-3) M) and atrial natriuretic peptide (10(-9) to 10(-7) M). These data are
      most simply explained by decreased arterial vascular smooth muscle sensitivity to
      NO at the level of soluble guanylate cyclase.

PMID- 7733351
TI  - Enhanced sympathetic reactivity to glutamate stimulation in medulla oblongata of
      spontaneously hypertensive rats.
AB  - The distribution and reactivity of vasomotor sites in the ventrolateral (VLM) and
      dorsomedial medulla (DMM) of stroke-prone spontaneously hypertensive rats
      (SHRSP), spontaneously hypertensive rats (SHR), and Wistar-Kyoto rats (WKY) were
      compared. Rats were anesthetized with alpha-chloralose and urethan. Baroreceptor
      denervation and vagotomy were performed. L-Glutamate (Glu, 10 mM, 30 nl) was
      microinjected into the DMM or VLM to identify vasoactive sites. The extent and
      the patterns of distribution of these sites in the three strains of rats were
      similar. The dose-response curve of the vasoactive site was studied with 1-500
      pmol of Glu. The maximum responses of blood pressure and renal sympathetic
      activity were larger and threshold doses of Glu were lower in hypertensive rats.
      The significance of the differences among the strains was analyzed before and
      after adjustment for baseline pressure or activity. Most of the differences were
      statistically significant before baseline adjustment. After baseline adjustment,
      many differences between the SHRSP and the WKY remained significant. However, the
      only significant difference detected between the SHR and the WKY was the
      threshold dose for eliciting renal sympathetic change in the caudal VLM. These
      results suggest that there may be a general increase in excitability of the
      vasomotor neurons in the medulla of the hypertensive rats.

PMID- 7733352
TI  - Exposure of energy-depleted rat trabeculae to low pH improves contractile
      recovery: role of calcium.
AB  - The beneficial effect of low pH during cardiac ischemia on reperfusion injury has
      often been attributed to its energy-saving effect due to inhibition of
      contraction. The role of low pH on Ca2+ accumulation and muscle tension was
      assessed in energy-depleted tissue by changing the pH of the medium from 7.4 to
      6.2 at onset of rigor development during metabolic inhibition (MI), i.e., in the
      energy-depleted phase. Cytosolic free Ca2+ ([Ca2+]i) and intracellular H+ (pHi)
      were measured in rat trabeculae at 20 degrees C with fura 2 and 2',7'
      bis(carboxyethyl)-5(6)-carboxyfluorescein, respectively, and tension was
      recorded. The preparations were energy depleted by stimulation at 1 Hz in glucose
      free Tyrode solution with 2 mM NaCN. Rigor developed within 20 min, indicating
      energy depletion. Resting [Ca2+]i was followed during 50 min (group I) or 100 min
      (group II) of rigor, and recovery was followed for 60 min in glucose-containing
      Tyrode solution at 0.2-Hz stimulation. Resting [Ca2+]i rose within 50 min (group
      I) but stabilized in the 50- to 100-min period (group II). All preparations from
      group I (n = 5) resumed contraction in the recovery period but in group II (n =
      10) 70% failed to recover, and [Ca2+]i remained elevated compared with those that
      recovered. An extracellular pH of 6.2, resulting in similar pHi, from onset of
      rigor development (group III) led to only a modest rise in [Ca2+]i during the 100
      min rigor period, and all preparations resumed contraction after approximately 3
      min in normal medium. ATP was very low in all groups at the end of MI but was
      still significantly lower in group II than in groups I and III. A beneficial
      energy-sparing effect of low pH during the rigor phase can therefore not be
      excluded. We conclude that 1) the capacity of trabeculae to recover from MI
      depends on the time period and magnitude of the [Ca2+]i rise in the energy
      depleted phase and 2) low pH in energy-depleted trabeculae protects against Ca
      overload, improving recovery after normalization of perfusion conditions.

PMID- 7733353
TI  - Role of cyclooxygenase inhibition and hyperoxia in regulating pulmonary perfusion
      in dogs.
AB  - To assess the roles of cyclooxygenase inhibition and hyperoxia in regulating
      pulmonary perfusion, we studied 13 dogs with diffuse granulomatous lung disease
      (DGLD) and 13 normal dogs. Baseline observations were obtained at fractional
      inspired O2 (FIO2) 0.21 and 1.0 and repeated after infusion of meclofenamate
      (Mec; n = 8) or saline (n = 5). Resistance to flow was evaluated from the
      pulmonary end-diastolic gradient (PDG) and by ohmic pulmonary vascular resistance
      (PVR). Distribution of blood flow was evaluated with sulfur hexafluoride in DGLD
      and with multiple inert gas alveolar ventilation-perfusion (VA/Q) plots in normal
      dogs. Before infusion, there were no differences between the saline and Mec
      groups at either FIO2. Saline induced no significant changes at either FIO2.
      After Mec in DGLD, PDG at FIO2 0.21 rose from 4 +/- 2 to 6 +/- 4 mmHg (P < 0.04),
      PVR increased from 297 +/- 98 to 484 +/- 181 dyn.s.cm-5.m-2 (P < 0.01), whereas
      shunt flow (Qs/Qt) fell form 13.6 +/- 12.0 to 6.2 +/- 5.3% (P < 0.03). At FIO2
      1.0 PDG rose from 3 +/- 2 to 4 +/- 3 mmHg (P < 0.02), PVR increased from 262 +/-
      78 to 374 +/- 139 dyn.s.cm-5.m-2 (P < 0.01), whereas Qs/Qt fell from 14.5 +/-
      13.3 to 6.4 +/- 5.2% (P < 0.02). After Mec in normal dogs, PDG at FIO2 0.21 rose
      from 3 +/- 1 to 4 +/- 1 mmHg (P < 0.015) and PVR increased from 256 +/- 92 to 340
      +/- 101 dyn.s.cm-5.m-2 (P < 0.05); at FIO2 1.0 PDG and PVR were unchanged from
      preinfusion levels. In normal dogs, no parameters of VA/Q changed significantly
      with hyperoxia or Mec. These data suggest that perivascular inflammation enhances
      perfusion in DGLD by elaboration of vasodilator prostaglandins (PG). By
      inhibiting PG synthesis, Mec selectively increases resistance in diseased lung at
      FIO2 0.21 and lowers Qs/Qt. In contrast, there was vasoconstriction without flow
      redistribution in normal dogs, suggesting that vasodilator PGs contribute to the
      low tone in the normal pulmonary bed. The vasodilation without flow
      redistribution in both models during hyperoxia after Mec suggests an effect of O2
      that is related neither to PG synthesis nor to hypoxic vasoconstriction.

PMID- 7733354
TI  - Protection of reoxygenated cardiomyocytes against hypercontracture by inhibition
      of Na+/H+ exchange.
AB  - Effects of Na+/H+ exchange inhibition and cytosolic acidosis on reoxygenated
      adult rat ventricular cardiomyocytes were investigated. Cells were incubated in
      anoxic media at pH 6.4 until pCa of < or = 5, intracellular pH (pHi) of 6.5, and
      cytosolic [Na+] of 50 mM were reached. On reoxygenation, medium pH was changed to
      7.4 to activate Na+/H+ exchange. In one group, 20 microM HOE-694, an inhibitor of
      Na+/H+ exchange, was added. With or without HOE-694, cytosolic Ca2+ and Na+
      returned to control levels within 10 min of reoxygenation. In the absence of HOE
      694, the pHi renormalized (to 7.2) within 8 min, but irreversible
      hypercontracture and transient Ca2+ oscillations were observed. In the presence
      of HOE-694, pHi stayed acidotic (at 6.5), hypercontracture was prevented, and
      Ca2+ oscillations were attenuated. When the Na+ pump was inhibited with 0.1 mM
      ouabain, even partial recovery of Ca2+ control became impossible unless HOE-694
      was added. Our conclusions are 1) activation of Na+/H+ exchange does not impair
      recovery of cytosolic Na+ and Ca2+ control unless activity of the sarcolemmal Na+
      pump is critically reduced, and 2) due to prolongation of cytosolic acidosis,
      inhibition of Na+/H+ exchange protects against reoxygenation-induced
      hypercontracture and cytosolic Ca2+ oscillations.

PMID- 7733355
TI  - Evaluation of methods for estimation of total arterial compliance.
AB  - Seven classic and recently proposed methods used for the estimation of total
      arterial compliance have been evaluated for their accuracy and applicability in
      different physiological conditions. The pressure and flow data are taken from a
      computer model that provides realistic simulations of the nonlinear-distributed
      systemic arterial tree. Besides the great flexibility in simulating different
      physiological or pathological cases, the major advantage of the computer model is
      that it allows precise knowledge of the pressure-dependent total arterial
      compliance, which is the variable of interest. The results show that the methods
      based on the two-element windkessel (WK) model are more accurate than those based
      on the three-element WK model. The classic exponential decay and the diastolic
      area method yield essentially similar results, and their compliance estimates are
      accurate within 10% except at high heart rates. The later part of diastole, i.e.,
      from the time that the systolic pressure wave has reached all peripheral beds,
      gives the best results. The newly proposed two-area and pulse pressure methods,
      both based on the two-element WK model, are accurate (errors in general < 10%)
      and can be applied to other locations in the arterial tree where the decay time
      and area method cannot. Methods based on the three-element WK model consistently
      overestimate total arterial compliance (> or = 25%). The errors in the methods
      based on the three-element WK model arise from the fact that the input impedance
      in that model deviates significantly from the true input impedance at low
      frequencies. The strong dependence of compliance on pressure (elastic
      nonlinearity) does not invalidate the compliance estimates.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7733356
TI  - Overflow of endogenous norepinephrine from PVH nucleus of DOCA-salt hypertensive
      rats.
AB  - Previous studies from this laboratory demonstrated that there was enhanced basal
      and evoked (K+ depolarization) overflow of endogenous norepinephrine (NE) into
      the perfusate of a push-pull cannula placed in the paraventricular nucleus of the
      hypothalamus (PVH) of conscious freely moving spontaneously hypertensive rat
      (SHR) compared with Wistar-Kyoto (WKY) or Sprague-Dawley (SD) rats. The present
      study was carried out to determine whether results obtained with SHR were
      specific to this genetic model of hypertension by examining NE release in
      deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt hypertension was
      produced in 8-wk-old uninephrectomized SD rats by administering a 50-mg DOCA
      Silastic pellet subcutaneously 7 days postnephrectomy and providing 0.9% NaCl +
      0.2% KCl drinking solution at libitum for 3 wk. Sham-implanted animals received
      normal tap water. Blood pressure was similar to that of 8- to 10-wk-old SHR.
      Basal release of NE as well as release after K+ added to the push-pull cannula or
      sodium nitroprusside or phenylphrine administered intravenously was determined.
      It was observed that there was no difference in basal overflow or after K+
      administration in DOCA-salt hypertensive rats compared with sham animals.
      Similarly, the increase in NE overflow due to sodium nitroprusside or the
      decrease due to phenylphrine was similar between DOCA-salt rats or sham controls.
      This was in sharp contrast to what was observed in SHR: basal or K(+)-evoked
      release was significantly greater in SHR than WKY, SD, DOCA-salt, or DOCA-sham
      controls. It is concluded that central noradrenergic activity involving the PVH
      is not altered in DOCA-salt hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733357
TI  - New insights into the physiology of retrograde cardioplegia delivery.
AB  - Although retrograde cardioplegia (RC) is being increasingly used in clinical
      practice, its physiology is unclear. Because the microvascular architecture of
      the coronary venous system is different from that of the arterial system, we
      hypothesized that myocardial perfusion would be different during RC compared with
      anterograde cardioplegia (AC) delivery. To better understand these differences,
      three groups of dogs were studied during similar RC and AC flow rates.
      Radiolabeled microsphere-derived microvascular flow underestimated total
      cardioplegia flow by 66% during RC. For the same flows, the first-pass extraction
      fractions of 201Tl and 99mTc were significantly less during RC compared with AC
      despite adjusting for microsphere loss. Myocardial contrast echocardiography
      (MCE), however, provided an accurate estimation of AC and RC flow rates. In
      addition, the rate of myocardial cooling for most of the left ventricular
      myocardium was similar for AC and RC at the same flow rates, as long as the flow
      rates were brisk. It is concluded that microvascular and nutrient flows are
      significantly lower at the same flow rates during RC compared with AC due to loss
      of RC at different microvascular sites. Unlike microspheres and diffusible
      radioisotopes, MCE can provide a reliable measure of myocardial flow during RC
      delivery. Furthermore, myocardial cooling is similar in most of the myocardium
      during high-flow RC and AC, which suggests that the clinical benefits of RC are
      probably related to myocardial cooling and that substrate replenishment may be
      better achieved at the same flow rates and myocardial temperatures with AC rather
      than RC.

PMID- 7733358
TI  - Cardiopulmonary baroreceptors modulate carotid baroreflex control of heart rate
      during dynamic exercise in humans.
AB  - Numerous studies have reported that, at rest, maximal carotid baroreflex gain is
      modulated by cardiopulmonary baroreceptors. The purpose of this study was to
      measure the maximal gain for carotid baroreflex control of heart rate (HR) and
      blood pressure [mean arterial pressure (MAP)] during dynamic exercise alone and
      when exercise was accompanied by two levels of cardiopulmonary baroreceptor
      unloading. Lower body negative pressure (LBNP) produced similar reductions in
      central venous pressure (CVP) at rest and during exercise. Baroreflex gain for HR
      at rest was not affected by low-level LBNP but was significantly increased by
      high-level LBNP [-0.31 +/- 0.05 to -0.57 +/- 0.23 beats.min-1.mmHg-1 carotid
      sinus pressure (CSP), no LBNP vs. high-level LBNP, P < 0.05]. Exercise combined
      with low- and high-level LBNP resulted in reflex HR gains (-0.83 +/- 0.44 and 
      0.83 +/- 0.17 beats.min-1.mmHg-1 CSP, low- vs. high-level LBNP, P < 0.05) that
      were significantly greater than the algebraic sum of the HR gain measured during
      exercise and LBNP alone. Neither exercise nor the two levels of LBNP
      significantly altered baroreflex gain for MAP. The slope relating HR gain to CVP
      at rest was significant (0.07 +/- 0.02 beats.min-1.mmHg CSP-1.mmHg CVP-1, P <
      0.01) and increased 114% during exercise (P < 0.05). A similar analysis of MAP
      gain found no difference in slope between rest and exercise (P > 0.05). Together
      these data indicate 1) a tonic inhibitory interaction between cardiopulmonary
      baroreceptors and carotid baroreflex control of HR during exercise, and 2) a
      nonlinear relationship between deactivation of cardiopulmonary baroreceptors and
      changes in carotid baroreflex gain. This interaction may improve overall
      cardiovascular regulation when central blood volume and/or CVP is reduced, as has
      been reported during prolonged exercise in the heat.

PMID- 7733359
TI  - Heterogeneity in role of endothelium-derived NO in pulmonary arteries and veins
      of full-term fetal lambs.
AB  - Endothelium-derived nitric oxide (EDNO) modulates fetal pulmonary vasoactivity.
      The role of EDNO in regulation of vasomotor tone in fetal pulmonary arteries vs.
      that in veins is not known. We have investigated the role of EDNO in the
      responses of pulmonary arteries and veins of full-term fetal lambs. Fourth
      generation pulmonary arterial and venous rings were suspended in organ chambers
      filled with modified Krebs-Ringer bicarbonate solution (95% O2-5% CO2 at 37
      degrees C), and their isometric force was measured. N omega-nitro-L-arginine had
      no effect on the resting tension of pulmonary arteries with endothelium but
      caused contraction of pulmonary veins with endothelium. The basal level of
      intracellular guanosine 3',5'-cyclic monophosphate (cGMP) of pulmonary veins with
      endothelium was higher than that of arteries with endothelium. In pulmonary
      arteries, bradykinin, but not acetylcholine, induced endothelium-dependent
      relaxation and an increase in cGMP content. In pulmonary veins, acetylcholine,
      but not bradykinin, induced endothelium-dependent relaxation and an increase in
      cGMP content. Agonist-induced maximal relaxation and increases in cGMP content
      were smaller in pulmonary arteries than in veins. All these endothelium-dependent
      responses were abolished by N omega-nitro-L-arginine. In tissues without
      endothelium, nitric oxide induced significantly less relaxation and less increase
      in cGMP content in pulmonary arteries than in pulmonary veins. All vessels
      relaxed similarly to 8-bromoguanosine 3',5'-cyclic monophosphate. Our data
      suggest that the role of EDNO in modulating tone differs between pulmonary
      arteries and veins in full-term fetal lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733360
TI  - Effects of pericardial pressure on systemic and coronary hemodynamics in dogs.
AB  - The effects of pericardial tamponade on coronary capacitance and coronary
      systemic hemodynamics were calculated in two groups of animals subjected to
      increases in pericardial pressure (PCP) up to approximately 20 mmHg. In one group
      (A), flow in the left circumflex artery was measured in the intact animal under
      conditions of increased PCP. In the second group (B), coronary artery perfusion
      pressure was maintained constant with a pump while PCP was increased. In group A
      increased PCP was accompanied by a decrease in arterial pressure. This resulted
      in a marked decrease in coronary blood flow after vasodilation but without a
      change in coronary vascular resistance. In group B there was no change in
      coronary flow or coronary vascular resistance with increased PCP. Microsphere
      distribution to the left ventricular wall showed less endocardial than epicardial
      flow but no change in going from low to high PCP. Characteristic impedance was
      altered in the group B animals after vasodilation at medium and high PCP,
      indicating a loss of reflection sites and probably increased vessel tethering.
      The coronary artery in a subgroup of group B animals was also perfused by left
      ventricular pressure, the time constants for coronary backflow showing an 8-12%
      decrease in capacitance with low and high PCP; these values represent minimal
      epicardial capacitances vs. total bed capacitance. A diastolic model for the
      values for resistance and capacitance in the coronary bed is suggested. As
      expected, most of the capacitance is in the venous bed and most of the resistance
      is in the arterial bed.

PMID- 7733361
TI  - Effects of aging on 24-h dynamic baroreceptor control of heart rate in ambulant
      subjects.
AB  - The effects of aging on the dynamic modulation of baroreflex sensitivity over 24
      h was assessed in eight elderly (mean age +/- SD, 63.9 +/- 3.2 yr) and in eight
      young (23.9 +/- 6.1 yr) mild or moderate essential hypertensive patients, who
      were subject to a 24-h intra-arterial (Oxford technique) blood pressure recording
      in ambulatory conditions. The sensitivity of baroreflex control of the heart rate
      was dynamically assessed by quantifying 1) the slope of the regression line
      between pulse interval (the reciprocal of heart rate) and systolic blood pressure
      changes over spontaneously occurring hypertension-bradycardia or hypotension
      tachycardia sequences (time domain analysis) and 2) the ratio between spectral
      powers of pulse interval and systolic blood pressure around 0.1 Hz (alpha
      coefficient: frequency domain analysis). The 24-h average sequence slope was
      lower in old than in young individuals (4.4 +/- 0.5 vs. 9.9 +/- 1.3 and 4.8 +/-
      0.7 vs. 8.4 +/- 1.4 ms/mmHg for hypertension-bradycardia and hypotension
      tachycardia sequences, respectively; P < 0.05 for both). Similar results were
      obtained by using the alpha-coefficient approach. The marked nighttime increase
      in baroreflex sensitivity observed in young individuals was much less evident in
      the elderly. Thus 24-h baroreflex sensitivity is markedly impaired by aging. The
      impairment becomes manifest also as an inability to increase baroreflex
      sensitivity at night.

PMID- 7733362
TI  - Human endothelial cell morphology and autacoid expression.
AB  - Human umbilical vein endothelial (HUVE) cells plated on plastic or gelatin-coated
      dishes grow as a "cobblestone" monolayer. By contrast, endothelial cells cultured
      on a complex matrix (e.g., Matrigel) form three-dimensional, capillary-like
      structures. In the current study, we verified the capillary phenotype of the
      latter structures and asked whether the morphological changes induced by
      extracellular matrix also affect human endothelial gene expression and function
      in vitro. Concentrations of cellular fibronectin, prostacyclin, and endothelin-1
      were measured in the conditioned media by enzyme-linked immunosorbent and
      radioimmunoassays. Steady-state concentrations of HUVE mRNA were estimated by
      reverse transcription-polymerase chain reaction and quantified by Northern
      analyses to assess fibronectin and endothelin-1 gene expression. We found that
      the subjacent extracellular matrix affects the morphology, proliferation, and
      differentiation of HUVE cells in vitro. Cells cultured on gelatin were more
      mitotically active, expressed significantly less cellular fibronectin, made
      similar amounts of prostacyclin, and secreted significantly more endothelin-1
      compared with the same cells grown on a Matrigel substrate.

PMID- 7733363
TI  - Endothelin regulation of cardiac contractility in absence of added endothelin.
AB  - Endothelin has a positive inotropic effect on cardiac muscle, but its role in the
      regulation of contraction in cardiac tissue is not clear, inasmuch as there has
      been no demonstration of endothelin regulation of contractility in the absence of
      added endothelin. To address this question, the changes in contractility of
      isolated rat ventricular trabeculae produced by endothelin and by BQ-123, an
      endothelin receptor A antagonist, were measured in tissues with different levels
      of contractility resulting from bathing the tissues for different lengths of
      time. The effect of endothelin depended on the extent to which tension had
      declined from its peak level: the greater the decline, the larger the increase in
      developed force produced by endothelin. The effect of BQ-123 also depended on the
      extent to which force had declined. The effects of the addition of endothelin or
      BQ-123 indicate the presence of substantial regulation of contractility due to
      basal secretion of endothelin: the degree of endothelin activity is greater in
      cardiac tissue generating more tension. Damage to the endocardial endothelium
      from a brief exposure to Triton X-100 reduced the response to BQ-123. The
      response to BQ-123 depends on the number of functioning endothelial cells. From
      the extent of the effect of endothelin or BQ-123, it appears that as much as 50%
      of total force-generating capacity of the tissue is sensitive to endothelin
      produced by the endothelial cells in the isolated heart. This stimulation of
      contractility is gradually lost in the isolated cardiac tissue, contributing to
      the progressive decline in developed force with time.

PMID- 7733364
TI  - Effects of Hoe-140 and ramiprilat on arteriolar tone and dilation to bradykinin
      in skeletal muscle of rats.
AB  - In skeletal muscle of pentobarbital sodium-anesthetized rats, the mechanism of
      action and possible role of the potent vasodilator bradykinin (BK) in regulation
      of arteriolar tone were investigated. Changes in diameter of third-order
      arterioles of cremaster muscle in response to topical administration of BK and
      other vasoactive agents were measured with an image-shearing monitor and recorded
      with video microscopy. All agonists were administered topically on the
      exteriorized muscle. With use of Hoe-140, a B2-receptor antagonist, the presence
      of kinin receptors in arterioles was studied. In control preparations, 10(-5) M
      arachidonic acid (AA), 0.5 x 10(-6) M acetylcholine (ACh), and 10(-5) M adenosine
      (ADO) evoked dilation of arterioles of up to 70% of resting diameter. BK (10(-9),
      10(-8), 10(-7), and 10(-6) M) elicited dose-dependent arteriolar dilations (1.3
      +/- 1.3, 4.1 +/- 0.5, 10.3 +/- 1.6, and 13.3 +/- 1.3 microns, respectively). In
      the presence of 10(-7) M Hoe-140, dilations to AA, ACh, and ADO were not
      affected, but those to 10(-9)-10(-7) M BK were eliminated or significantly
      inhibited (10(-6) M BK: to 2.9 +/- 1.8 microns). Also, whereas Hoe-140
      significantly reduced basal arteriolar diameters (from 16.7 +/- 0.9 to 13.8 +/-
      1.1 microns, P < 0.05), it did not affect constrictions to
      norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733365
TI  - Differential hemodynamic effects of L-NMMA in endotoxemic and normal dogs.
AB  - We studied the differential hemodynamic effects of N omega-monomethyl-L-arginine
      (L-NMMA), an inhibitor of nitric oxide (NO) synthesis, in normal and endotoxemic
      dogs and examined its activity across the venous, pulmonary, and systemic
      circulations. Survival was used to determine therapeutic efficacy. In both normal
      and endotoxemic animals, L-NMMA similarly increased systemic (P = 0.01) and
      pulmonary (P = 0.047) vascular resistance, marginally increased mean arterial
      pressure (P = 0.07), and decreased oxygen delivery (P = 0.01) compared with
      normal saline. In contrast, the effect of L-NMMA on mean pulmonary arterial
      pressure, central venous pressure, and pulmonary capillary wedge pressure was
      different in endotoxemic than in normal animals (P < 0.05), but this differential
      effect occurred > 6 h after endotoxin challenge. L-NMMA (1-10 mg.kg-1.h-1) did
      not significantly increase survival rates or times in endotoxemic animals, but
      the highest dose decreased survival times (P < 0.05). Thus the effect of L-NMMA
      was similar on the systemic arterial circulation in endotoxemic dogs compared
      with normal dogs but was increased in the venous and pulmonary vascular beds
      after endotoxin, suggesting that the induction of NO production was greater in
      low-resistance vessels. We were unable to show that nonselective inhibition of NO
      production was beneficial in endotoxemic dogs.

PMID- 7733366
TI  - Modulation of oxidized low-density lipoprotein-induced microvascular dysfunction
      by nitric oxide.
AB  - The objectives of this study were to determine 1) whether the leukocyte
      endothelial cell adhesion in postcapillary venules elicited by copper-oxidized
      low-density lipoproteins (Cu-LDL) is accompanied by enhanced vascular albumin
      leakage and mast cell degranulation and 2) whether nitric oxide (NO) donors
      attenuate the Cu-LDL-induced microvascular dysfunction. Infusion of Cu-LDL, but
      not normal LDL, caused significant increases in leukocyte rolling, adherence,
      emigration, mast cell degranulation, and an enhanced albumin leakage in rat
      mesenteric venules. Treatment with the NO donors sodium nitroprusside and
      spermine-NO or pretreatment with superoxide dismutase or L-arginine significantly
      reduced the Cu-LDL-induced leukocyte adherence, emigration, mast cell
      degranulation, and albumin leakage, whereas spermine and D-arginine had no
      effect. These results indicate that NO protects the microvasculature against the
      deleterious effects of oxidized LDL, an effect that may be related to NO's
      ability to reduce leukocyte-endothelial cell adhesion and/or prevent mast cell
      degranulation.

PMID- 7733367
TI  - Oxidative injury of coronary venular endothelial cells depletes intracellular
      glutathione and induces HSP 70 mRNA.
AB  - Vascular endothelium is one of the first tissues exposed to reactive oxygen
      species produced during myocardial ischemia-reperfusion. Bovine coronary venular
      endothelial cells (CVEC) were evaluated for intracellular glutathione (GSH)
      levels and heat shock protein 70 (HSP 70) mRNA and protein during in vitro
      oxidative stress. CVEC were incubated with 0.01875 U/ml xanthine oxidase (XO) and
      0.5 mM hypoxanthine (HX) for 30 min and then allowed to recover for 0, 1, 2, or 3
      h. Relative GSH levels were determined by evaluation of monochlorobimane
      fluorescence. GSH fluorescence was significantly lower in CVEC treated with XO+HX
      for 30 min than in controls. GSH fluorescence was also decreased in heat-shocked
      CVEC. After oxidative stress, GSH levels were higher than in controls at 1 h, but
      by 2 or 3 h after treatment, GSH fluorescence fell below control values. HSP 70
      mRNA was induced in CVEC by a 30-min treatment with XO+HX exposure. These data
      suggest that CVEC respond to oxidative stress by reducing intracellular GSH
      levels and inducing HSP 70 mRNA, although significant increases in HSP 70 protein
      were not detected at the time points tested.

PMID- 7733368
TI  - Palmitate uptake by cardiac myocytes and endothelial cells.
AB  - The mechanisms regulating the cellular uptake of long-chain fatty acids are
      poorly understood. Although there is evidence that hepatocytes facilitate the
      uptake of ligands from the protein-bound fraction, it is not known whether
      cardiac myocytes also facilitate the uptake process. The present studies were
      designed to address the role of albumin in the uptake of long-chain fatty acids
      by cardiac myocytes isolated from adult male rats. At low albumin concentrations
      (1 microM), the myocyte palmitate clearance rate did not exceed that predicted by
      the diffusion-reaction model. At high albumin concentrations (300 and 600
      microM), the clearance ratio test was used to determine whether myocytes
      facilitate the uptake of palmitate. As with the low albumin concentrations, the
      diffusion-reaction model accounted for the overall clearance rates. Because
      endothelial cells might be involved in enhancing fatty acid transport into
      myocytes, we also determined the effects of endothelial cells on palmitate uptake
      by cardiac myocytes. Based on cell number, the palmitate clearance rate by
      endothelial cells in the presence of albumin was only 7% of the cardiac myocyte
      clearance rate. Combining the endothelial cells with the myocytes did not result
      in any synergistic effect on the palmitate clearance rate.

PMID- 7733369
TI  - Impaired microvascular response to graded coronary occlusion in diabetic and
      hyperglycemic dogs.
AB  - The hypothesis that coronary microvascular responses to ischemia are impaired in
      diabetes was tested in 9 alloxan-treated (60 mg/kg i.v.), 8 hyperglycemic, and 16
      control dogs. Arteriolar diameters were measured in intact beating left ventricle
      by use of stroboscopic epi-illumination and intravital microscopy with
      fluorescence microangiography. Coronary arterial diameters were measured during
      graded reductions in mean coronary perfusion pressure to 60 +/- 1 (SE) mmHg (mild
      stenosis), 39 +/- 1 mmHg (severe stenosis), and 26 +/- 1 mmHg (coronary artery
      occlusion). Blood glucose levels were 95 +/- 5, 264 +/- 17, and 277 +/- 15 mg/dl
      in control, diabetic, and hyperglycemic animals, respectively. In control dogs,
      arteriolar microvessels (< 100 microns) dilated (24 +/- 5, 31 +/- 5, and 26 +/-
      6% change in diameter from baseline during mild stenosis, severe stenosis, and
      coronary occlusion, respectively). Diabetes or hyperglycemia prevented the normal
      dilatory response and resulted in decreases in microvascular diameter during
      decreases in perfusion pressure (-2 +/- 3, -4 +/- 3, and -15 +/- 4% change in
      diameter in diabetic animals and -11 +/- 2, -9 +/- 4, and -8 +/- 5% change in
      diameter in hyperglycemic animals). Large-vessel (> 100 microns) dilation was
      also significantly impaired in diabetic and hyperglycemic animals. Myocardial
      perfusion was significantly lower in the epicardium during a severe stenosis in
      diabetic and hyperglycemic than in control dogs. Because the ATP-sensitive K+
      (KATP) channel mediates this response in normal animals, we tested the hypothesis
      that KATP channel responsiveness is impaired in diabetes and
      hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733370
TI  - Critical intracellular O2 in myocardium as determined by 1H nuclear magnetic
      resonance signal of myoglobin.
AB  - The 1H nuclear magnetic resonance (NMR) signal of tissue myoglobin has provided
      an opportunity to determine the critical O2 level in saline-perfused myocardium
      at room temperature. Above the intracellular PO2 of 4 mmHg, the myocardium
      exhibits no sign of hypoxia. At 4 mmHg, the rate pressure product (RPP)
      decreases, and the lactate formation rate, measured enzymatically, increases.
      However, O2 consumption and the 31P-NMR signal of phosphocreatine level remain
      relatively constant until the cellular PO2 reaches 2 mmHg. The ATP signal
      intensity dips only when cellular O2 reaches 0.8 mmHg, while pH remains unchanged
      at 7.2. The sequential nature of the cellular response to limiting O2, starting
      with alterations in the lactate formation rate and RPP, indicates that NADH,
      rather than ADP, signals tissue hypoxia. Moreover, the study suggests that the O2
      gradient from capillary to cell is larger than that from cytosol to mitochondria.

PMID- 7733371
TI  - Methodology of spontaneous baroreflex relationship assessed by surrogate data
      analysis.
AB  - We tested the hypothesis that the spontaneous beat-by-beat interactions of
      systolic blood pressure (SBP) and R-R interval reflected true baroreflex events
      rather than chance interactions. Original data sets of 1,024 heartbeats obtained
      in seated rest from six healthy subjects [R-R interval = 953 +/- 94 (+/- SE) ms]
      were compared with isospectral [generated by a windowed (inverse) Fourier
      transform with phase randomization] and isodistribution (data points randomly
      shuffled) surrogate data sets. The isospectral data set was used to test for
      random phase relationships, and the isodistribution data set was used for effects
      of white noise between SBP and R-R interval. Spontaneous baroreflex sequences
      were defined as three or more beats in which SBP and the R-R interval of the same
      (lag 0), next (lag 1), or next following (lag 2) beat changed in the same
      direction. The total number of baroreflex sequences in the original data was
      significantly greater than the surrogates (P < 0.001). In the original data,
      there were significantly (P < 0.001) more lag 0 than lag 1 or lag 2 baroreflex
      sequences. Therefore, these results indicated that spontaneous baroreflex
      sequences represented physiological rather than chance interactions and that
      baroreflex responses can occur within the same beat.

PMID- 7733372
TI  - Change in phase relationship between SBP and R-R interval during lower body
      negative pressure.
AB  - We have investigated the hypothesis that beat-by-beat interaction of systolic
      blood pressure (SBP) to R-R interval (the spontaneous baroreflex) is dependent on
      the length of the R-R interval. Data were collected from eight healthy men while
      heart rate was slow (R-R interval 1,043 +/- 34 ms) and accelerated (R-R interval
      804 +/- 18 ms) by application of lower body negative pressure (LBNP greater than
      or equal to -40 mmHg). Time series data of SBP and R-R interval were searched for
      spontaneous baroreflex sequences in which R-R interval changed in the same (lag
      0), next (lag 1), or next following (lag 2) beat as SBP. This phase relationship
      was also quantified by cross-spectral analysis. At rest, 85% of all spontaneous
      baroreflex sequences occurred with no lag (lag 0). With LBNP, there was a
      significant reduction in the number of lag 0 sequences (26%), whereas lag 1 and
      lag 2 sequences increased (10-26% and 5-29%, respectively). Cross-spectral phase
      also changed significantly from -2.3 +/- 6.3 degrees at rest to 70.5 +/- 7.4
      degrees during LBNP. These data supported the hypothesis that the lag of a
      baroreflex event was dependent on the prevailing R-R interval.

PMID- 7733373
TI  - Pregnancy-induced alterations of neurogenic constriction and dilation of human
      uterine artery.
AB  - The responses to electrical field stimulation (EFS) of perivascular nerves in
      human uterine arteries were characterized. The arteries were removed from
      pregnant and nonpregnant patients undergoing hysterectomy. Tetrodotoxin,
      guanethidine, and phentolamine blocked EFS (2 min, 80 V, 0.1-ms duration)-induced
      constriction. The constrictions and the endogenous norepinephrine levels were
      lower (P < 0.01) in uterine arteries from pregnant than from nonpregnant
      patients. When arterial rings were precontracted, the response to EFS was
      biphasic, consisting of an initial constriction followed by a postconstriction
      relaxation. The EFS-induced relaxation was endothelium independent and was
      greater (P < 0.01) in uterine arteries from pregnant than from nonpregnant
      patients. The relaxation was enhanced by guanethidine and superoxide dismutase,
      inhibited by nitric oxide synthase inhibitors, blocked by tetrodotoxin, and
      unaffected by atropine, propranolol, or indomethacin. The results demonstrate
      that human uterine arteries respond to EFS with contraction and relaxation and
      that these responses may be mediated, respectively, by norepinephrine and, in
      part, by nitric oxide released from periarterial nerves. The decrease in
      neuronally mediated uterine arterial constriction and the increase in dilation
      could be physiological mechanisms for ensuring appropriate uteroplacental
      perfusion.

PMID- 7733374
TI  - Myocyte performance during evolution of myocardial infarction in rats: effects of
      propionyl-L-carnitine.
AB  - To determine whether alterations in the mechanical properties and calcium
      transients of myocytes are important factors in the evolution of the
      postinfarcted heart, these physiological parameters were measured in the viable
      muscle cells of the left ventricle 6 h, 2-3 days, 1 wk, and 1 mo after coronary
      artery occlusion and the documentation of left ventricular failure. In addition,
      the effects of propionyl-L-carnitine (PLC) on shortening properties and calcium
      dynamics of single myocytes were established to demonstrate whether the potential
      increase in ATP generation by this intervention improved myocyte cell function.
      Myocardial infarction was associated with a progressive increase in length of the
      spared myocytes, whereas the changes in myocyte diameter were apparent only at
      the 1-mo interval. Mechanically, myocyte shortening was decreased 43% at 6 h, 34%
      at 2-3 days, 26% at 1 wk, and 41% at 1 mo after infarction. Similar abnormalities
      were noted in the velocity of myocyte shortening. Peak systolic calcium was
      decreased at all intervals after infarction. In contrast, diastolic calcium
      remained within control values. PLC was capable of ameliorating the mechanical
      behavior and calcium transients of myocytes, particularly 1 mo after infarction.
      Thus alterations in muscle cell performance may be important determinants in the
      development and progression of ischemic cardiomyopathy, and interventions
      improving myocyte contractility may interfere with the unfavorable outcome of the
      disease.

PMID- 7733375
TI  - Na+/Ca2+ exchange current density in cardiac myocytes from rabbits and guinea
      pigs during postnatal development.
AB  - It has been proposed that the activity of the cardiac sarcolemmal Na+/Ca2+
      exchanger may be greatest in developing animals before the sarcoplasmic reticulum
      (SR) reaches functional maturity. Experiments were performed in rabbits, which
      have a sparse SR at birth, and in newborn guinea pigs, which exhibit a more
      extensive SR. Whole cell voltage clamp techniques were used to characterize the
      Ni(2+)-sensitive Na+/Ca2+ exchange current in single freshly isolated cardiac
      myocytes. Na+/Ca2+ exchange current was measured from a holding potential of -40
      mV by using a slow-ramp voltage protocol (-120 to +60 mV, 0.09 V/s) in the
      presence of Ba2+, Cs+, tetraethylammonia, D-600, and ouabain to block Ca2+, Na+,
      and K+ currents. Experiments in developing rabbits (1-22 days old) demonstrated
      that Na+/Ca2+ exchange current density was greatest at 1-4 days and declined
      rapidly over the first 3 wk of age. In contrast, Na+/Ca2+ exchange current
      density in newborn guinea pig myocytes did not differ from that recorded in
      adults. These results confirm that Na+/Ca2+ exchange is functional at birth in
      both rabbits and guinea pigs. The species-related difference in the ontogeny of
      Na+/Ca2+ exchange is consistent with the concept that Na+/Ca2+ exchange assumes a
      relatively greater role in newborn animals with a sparse SR.

PMID- 7733376
TI  - Na+/Ca2+ exchange and cell contraction in isolated neonatal and adult rabbit
      cardiac myocytes.
AB  - Recent studies have demonstrated a relative deficiency in voltage-gated Ca2+
      currents (ICa) in immature myocardium. We hypothesized that contraction in
      developing heart results in part from Ca2+ influx via "reverse" Na+/Ca2+ exchange
      current (INa/Ca). Accordingly, INa/Ca and cell contraction amplitude were
      measured in single neonatal and adult rabbit ventricular myocytes. INa/Ca was
      dependent on Ca2+ concentration, Na+ concentration, and membrane potential and
      was blocked by 5 mM Ni2+ but not by the Ca(2+)-channel blocker nifedipine. In
      neonatal cells, contraction amplitude reached a plateau for depolarizations
      positive to 0 mV. In adult myocytes, contraction amplitude was maximal at 0 mV
      and decreased at positive membrane potentials. Inhibition of ICa with nifedipine
      did not affect maximal contraction amplitude in neonatal myocytes but almost
      completely suppressed contraction of adult cells. These data suggest that Ca2+
      influx via ICa is not required for contraction of neonatal rabbit cardiac
      myocytes. Moreover, Ca2+ influx via reversal of the Na+/Ca2+ exchange mechanism
      may provide a significant portion of the Ca2+ regulating cell contraction,
      especially during depolarization to positive membrane potentials.

PMID- 7733377
TI  - Influence of sleep and myometrial activity on systemic and uteroplacental
      hemodynamics in pregnant ewes.
AB  - Little is known about the influence of sleep on systemic and uteroplacental
      hemodynamics during pregnancy. Experiments were therefore carried out on six
      chronically instrumented pregnant ewes (125-133 days of gestation) to investigate
      the influence of sleep on systemic and uteroplacental hemodynamics. Because
      nonlabor myometrial activity influences uteroplacental hemodynamics, we made
      measurements during quiet wakefulness, quiet sleep, and active sleep in the
      presence and absence of myometrial activity. Cardiac output, heart rate, and
      systemic arterial pressure were decreased in active sleep compared with quiet
      wakefulness; these variables were not significantly altered by myometrial
      activity. The interaction between sleep and myometrial activity was such that the
      lowest values of uteroplacental blood flow, as estimated from middle uterine
      artery blood flow to the pregnant uterine horn and, hence, uteroplacental oxygen
      delivery occurred during active sleep in the presence of myometrial activity
      (i.e., decreased approximately 19% compared with quiet wakefulness and the
      absence of myometrial activity). Further investigation is required to determine
      the possible fetal consequences of a reduced uteroplacental perfusion in the
      presence of myometrial activity during sleep.

PMID- 7733378
TI  - Activation of thrombin receptor increases intracellular Na+ during myocardial
      ischemia.
AB  - Recent evidence indicates that factors involved in the activation of the
      coagulation system eliciting an intracoronary thrombus may contribute importantly
      to arrhythmogenesis during acute myocardial ischemia. In the present study, the
      influence of the thrombin receptor activating peptide, SFLLRNPNDKYEPF (SFLL), on
      intracellular Na+ ([Na+]i) and tissue lysophosphatidylcholine (LPC) content
      during ischemia was investigated in an isolated, blood-perfused rabbit papillary
      muscle preparation. During normoxic perfusion, [Na+]i, determined by an
      intracellular Na(+)-selective electrode, was 11.6 +/- 0.2 mM (n = 14) in the
      presence of a physiological concentration of LPC (125 microM) bound to albumin
      (control group). The addition of SFLL (100 microM, n = 12) to the LPC-containing
      perfusate had no significant additional effects on [Na+]i, twitch tension, action
      potential duration, or tissue LPC content. During zero flow ischemia, [Na+]i in
      the control group rose to 15.5 +/- 1.4 mM (P < 0.05) at 6 min, whereas [Na+]i in
      the group treated with SFLL increased rapidly from the preischemic value of 11.7
      +/- 0.3 to 23.5 +/- 1.9 mM (P < 0.01 compared with that in the control group)
      over the same time period. This rapid rise in [Na+]i was associated with a
      greater accumulation of tissue LPC, an arrhythmogenic lipid metabolite, and the
      development of early ventricular arrhythmias. These results indicate that an
      increase in [Na+]i induced by activation of the thrombin receptor, likely
      mediated through its effect on the accumulation of LPC within ischemic
      myocardium, may be responsible for arrhythmogenesis during myocardial ischemia
      secondary to activation of the coagulation system.

PMID- 7733379
TI  - Effect of intracellular and extracellular acidosis on sodium current in
      ventricular myocytes.
AB  - Conduction slowing is an essential element in the generation of ischemic
      ventricular arrhythmias and is determined in part by the inward Na+ current
      (INa). Because intracellular acidosis is an early consequence of ischemia, we
      hypothesized that lowering intracellular pH (pHi) would reduce or kinetically
      modulate INa and thus affect cardiac conduction. To test this hypothesis, the
      whole cell patch-clamp method was used to measure INa in neonatal rat ventricular
      myocytes exposed to varying extracellular pH (pHo 6.4-7.4), while perfusing the
      cells with acidic solutions (pHi 6.2-7.2). With simultaneous acidification of pHo
      and pHi there was a progressive increase in time to peak current, a 31% decrease
      in peak INa (298 +/- 18 to 206 +/- 16 pA/pF), and a complex slowing of
      inactivation kinetics. At the most extreme levels of acidification, there was a 5
      mV hyperpolarizing shift in steady-state inactivation and a 6-mV depolarizing
      shift in activation. Independent changes of pHo and pHi indicate that the
      reduction of peak INa is a function of pHo. However, steady-state inactivation is
      modulated by pHi. The time course of activation and inactivation appears to
      depend on both pHo and pHi. We conclude that both intracellular and extracellular
      acidosis are significant but distinct modulators of INa amplitude and kinetics in
      cardiac myocytes.

PMID- 7733380
TI  - Method for isolation of human ventricular myocytes from single endocardial and
      epicardial biopsies.
AB  - The study of adult human ventricular cells has been limited by tissue
      availability. In this study we describe techniques for the isolation of Ca(2+)
      tolerant adult human ventricular cells from both transvenous endomyocardial and
      epicardial biopsies. Ca(2+)-tolerant cells were obtained from 80% of the biopsies
      processed. Although the yield of Ca(2+)-tolerant myocytes from either type of
      biopsy was low (1-5%), myocytes with normal resting potentials and action
      potentials can be obtained from single biopsy specimens, providing a source of
      normal human myocytes for electrophysiological study. Resting potentials (Vrest)
      were recorded in 41 isolated right ventricular endomyocardial cells at 37 degrees
      C. Sixteen cells were depolarized (Vrest = -26 +/- 13 mV), and 25 cells had
      normal resting potentials (Vrest = -84 +/- 6 mV). Action potentials were recorded
      in 16 cells. At a pacing cycle length of 1 s, 4 cells had prolonged action
      potential duration at 90% (APD90, 718 +/- 26 ms) and 10 cells had normal APD90
      (381 +/- 94 ms) compared with those recorded from intact right ventricular septal
      trabeculae from explanted hearts. Voltage-clamp studies of isolated human
      ventricular myocytes obtained from these biopsies document the presence of
      currents previously reported from cells isolated from explanted hearts.

PMID- 7733381
TI  - Subcellular distribution of shear stress at the surface of flow-aligned and
      nonaligned endothelial monolayers.
AB  - The stresses acting on the luminal surface of endothelial cells due to shear flow
      were determined on a subcellular scale. Atomic force microscopy was used to
      measure the surface topography of confluent endothelial monolayers cultured under
      no-flow conditions or exposed to steady shear stress (12 dyn/cm2 for 24 h). Flow
      over these surface geometries was simulated by computational fluid dynamics, and
      the distribution of shear stress on the cell surface was calculated. Flow
      perturbations due to the undulating surface produced cell-scale variations of
      shear stress magnitude and hence large shear stress gradients. Reorganization of
      the endothelial surface in response to prolonged exposure to steady flow resulted
      in significant reductions in the peak shear stresses and shear stress gradients.
      From the relationship between surface geometry and the resulting shear stress
      distribution, we have defined a hydrodynamic shape factor that characterizes the
      three-dimensional morphological response of endothelial cells to flow. The
      analysis provides a complete description of the spatial distribution of stresses
      on individual endothelial cells within a confluent monolayer on a scale relevant
      to the study of physical mechanisms of mechanotransduction.

PMID- 7733382
TI  - Ion transport in gills of the euryhaline fish Gillichthys mirabilis is
      facilitated by a phosphocreatine circuit.
AB  - The function of creatine kinase (CK) isozymes in energy metabolism and the short
      term regulation of active ion transport in gills of the euryhaline teleost
      Gillichthys mirabilis was investigated. After a transfer of fish from regular
      seawater [36 parts/thousand (ppt)] to hypersaline water (60 ppt), the plasma
      osmolality increased significantly from 361.0 +/- 5.2 to 434.2 +/- 20.6
      mosmol/kgH2O within 2 h and was regulated down to 391.8 +/- 11.3 mosmol/kgH2O
      within 12 h. Although the ATP concentration in the gill tissue remained
      unchanged, the creatine concentration increased significantly from 17.3 +/- 3.2
      to 37.6 +/- 5.9 nmol/mg protein within 2 h after the salinity change. CK and
      Na(+)-K(+)-adenosinetriphosphatase-(Na(+)-K(+)-ATPase) activities were unchanged
      48 h after transfer. Independent of salinity, the activities of CK were three to
      seven times those of the Na(+)-K(+)-ATPase, and the creatine concentration in the
      gill was at least one order of magnitude higher than the ATP concentration. The
      occurrence of muscle-type CK (CK-M), brain-type CK, and mitochondrial CK was
      demonstrated. CK-M was predominant in gills (59 +/- 7.1% of total CK activity).
      Evidence for a direct functional coupling between CK and Na(+)-K(+)-ATPase was
      obtained with permeabilized gill cells, by using the CK inhibitor iodoacetamide,
      which abolishes the competitive channeling of ADP from the external pyruvate
      kinase reaction to the endogeneous CK reaction in a coupled in situ Na(+)-K(+)
      ATPase assay. Our results show the significance and the central regulatory role
      for energy metabolism and adaptive ionoregulation of a phosphocreatine-CK circuit
      in situations of high and fluctuating energy demands for euryhaline fishes.

PMID- 7733383
TI  - Different outcomes in biological experiments involving weak EMFs: is chaos a
      possible explanation?
AB  - Reports of biological effects induced by electromagnetic fields (EMFs) are
      sometimes not confirmed in subsequent similar studies. It is possible that the
      fields in these studies were actually transduced by the biological systems and
      that the pattern of apparently conflicting results is not a valid inference but
      arises from the conceptual framework. The question was studied in connection with
      effects of EMFs on body weight of animals. Previous studies revealed no
      consistent effect on mean body weight, but reexamination of the data suggested
      that variance in body weight was consistently altered after long-term exposure.
      In the present study, 0.5 kV/m, 60 Hz, was applied continuously from conception
      to maturity in successive generations of mice; as hypothesized, mean body weight
      was not consistently affected but variance in body weight was altered. The
      occurrence of transduction can therefore be inferred from the effect on variance
      despite the absence of a consistent effect on the mean. These results and those
      from previous similar studies support an interaction model in which the
      observability of posttransduction biological changes in the mean is strongly
      dependent on the initial conditions, in analogy with the importance of initial
      conditions in fixing the final state in deterministic chaos. Thus, at least with
      regard to EMF effects on body weight, a change from a linear (dose-effect) to a
      nonlinear paradigm is sufficient to explain the anomalous pattern of some
      reported studies.

PMID- 7733384
TI  - Gurmarin inhibition of sweet taste responses in mice.
AB  - The inhibitory effects of gurmarin (a peptide isolated from the leaves of Gymnema
      sylvestre) on sweet taste responses were studied by examining the chorda tympani
      nerve responses to various taste substances before and after lingual treatment
      with gurmarin in C57BL and BALB mice. Treatment with gurmarin at 3 micrograms/ml
      or more selectively suppressed responses to sucrose without affecting responses
      to NaCl, HCl, and quinine in C57BL mice, whereas gurmarin at 100 micrograms/ml
      did not significantly suppress sucrose responses in BALB mice. Responses to
      various sweet substances in C57BL mice decreased to approximately 45-75% of
      control after gurmarin, and the suppressive effect of gurmarin was reversible.
      The profile of the residual responses of C57BL mice to various sweeteners after
      gurmarin was almost identical to that of BALB mice, which was hardly affected by
      gurmarin. These results strongly suggest that there are at least two types of
      sweet taste receptors in mice, gurmarin-sensitive and -insensitive. Probably,
      C57BL and BALB mice share an identical gurmarin-insensitive receptor, and C57BL
      mice also have a gurmarin-sensitive receptor.

PMID- 7733385
TI  - Metabolic, hormonal, and hemodynamic changes induced by metabotropic excitatory
      amino acid agonist (1S,3R)-ACPD.
AB  - The purpose of the present study was to determine whether central administration
      of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), a selective
      metabotropic glutamate receptor agonist, would stimulate glucose metabolism,
      activate the hypothalamic-pituitary-adrenal axis, or influence pancreatic
      endocrine secretion. Intracerebroventricular injection of ACPD increased arterial
      glucose levels by 60% within 15 min, which were sustained throughout the 3-h
      experimental protocol. This hyperglycemia resulted from an early increase in
      hepatic glucose production (HGP, 88%) that exceeded the increase in glucose
      uptake by peripheral tissues (66%). Stimulation of glucose metabolism was
      associated with transient elevations in plasma insulin (145%) and glucagon (3
      fold) levels and more sustained elevations in corticosterone (141%), epinephrine
      (3- to 5-fold), and norepinephrine (32-110%). Intravenous infusion of alpha- and
      beta-adrenergic antagonists prevented the ACPD-induced increase in glucose
      metabolism. Arterial blood pressure, cardiac index, and total peripheral
      resistance were not altered after ACPD. Overall, the changes in regional blood
      flow were unremarkable, although ACPD did increase blood flow to the liver (2
      fold) and heart (48%) and decrease flow to the stomach (33%). These results
      indicate that central administration of ACPD 1) enhances HGP, which is primarily
      mediated by adrenergic stimulation; 2) increases glucose uptake by peripheral
      tissues, which appears to be mediated by both hyperinsulinemia and hyperglycemia;
      3) stimulates pancreatic and adrenal hormone secretion independent of adrenergic
      activation; and 4) produces minimal changes in regional blood flow that cannot
      explain the glucose metabolic response produced by ACPD.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7733386
TI  - Osmotic stimulation of vasopressin mRNA content in the supraoptic nucleus
      requires synaptic activation.
AB  - The role of synaptic input to the vasopressin neurons in hypertonicity-induced
      increase in vasopressin mRNA content was evaluated. Synaptic connection with the
      anterior hypothalamus is required for hypertonicity to increase vasopressin
      release. However, the potential for other mechanisms to induce the increase in
      vasopressin mRNA content is suggested by the fact that hypertonicity induces
      depolarization of supraoptic neurons independently of synaptic input. Explants of
      the hypothalamoneurohypophysial system were used to study the effect of
      depolarization and hypertonicity in the presence and absence of nonspecific
      synaptic blockade by 15 mM MgSO4 or blockade of excitatory amino acid receptors
      with kynurenic acid. Vasopressin release and mRNA content were increased by
      depolarization with 40 mM KCl and by exposure to hypertonicity (P < 0.05). Basal
      and osmotically stimulated vasopressin release was decreased by MgSO4 and by
      kynurenic acid. Both agents prevented the hypertonicity-induced increase in
      vasopressin mRNA content. Thus either synaptic input or increased VP release is
      required for hypertonicity to increase vasopressin mRNA, and excitatory amino
      acids are implicated in this response.

PMID- 7733387
TI  - Intrapericardial denervation: responses to water immersion in rhesus monkeys.
AB  - Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and
      endocrine alterations associated with 120 min of head-out water immersion. Five
      animals underwent complete intrapericardial denervation using the Randall
      technique, while the remaining six monkeys served as intact controls. Each animal
      was chronically instrumented with an electromagnetic flow probe on the ascending
      aorta, a strain gauge pressure transducer implanted in the apex of the left
      ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV.
      During immersion, LV end-diastolic pressure, urine flow, glomerular filtration
      rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each
      increased (P < 0.05) for intact and denervated monkeys. There were no alterations
      in free water clearance in either group during immersion, yet fractional
      excretion of free water increased (P < 0.05) in the intact monkeys. Plasma renin
      activity (PRA) decreased (P < 0.05) during immersion in intact monkeys but not
      the denervated animals. Plasma vasopressin (PVP) concentration decreased (P <
      0.05) during the first 30 min of immersion in both groups but was not
      distinguishable from control by 60 min of immersion in denervated monkeys. These
      data demonstrate that complete cardiac denervation does not block the rise in
      plasma ANP or prevent the natriuresis associated with head-out water immersion.
      The suppression of PVP during the first minutes of immersion after complete
      cardiac denervation suggests that extracardiac sensing mechanisms associated with
      the induced fluid shifts may be responsible for the findings.

PMID- 7733388
TI  - Effect of L-alanine and ouabain on membrane conductances and apical membrane
      potential in Aplysia intestine.
AB  - The proximal intestine of Aplysia californica was employed to assess the effect
      of alanine absorption on apical membrane K+ conductance (GKa) and basolateral
      membrane conductance (Gb) and the role of the electrogenic Na(+)-K(+)
      adenosinetriphosphatase (Na+ pump) in the repolarization of apical membrane
      electrical potential difference (Va) after alanine-induced depolarization.
      Addition of 50 mM L-alanine (isosmotic substitution for mannitol) to the apical
      superfusate depolarized Va, reduced the ratio of apical to basolateral membrane
      resistances (Ra/Rb), and stimulated short-circuit current (Isc). Following these
      initial events, Va repolarized, Ra/Rb increased, and there was a slight decline
      in Isc. Apical high-K+ artificial seawater revealed an alanine-induced increase
      in GKa. Washout of alanine from the apical solution increased Ra/Rb above the
      prealanine control value. Thus alanine absorption is accompanied by an increase
      in Gb. Basolateral 0.1 mM ouabain abolished alanine-stimulated Isc but had little
      effect on Va ( < 3 mV depolarization) either before or after exposure to alanine.
      The repolarization of Va was not affected in tissues superfused with 0.1 mM
      basolateral ouabain for approximately 3 min even though the alanine-stimulated
      increase in Isc was abolished. Therefore, the electrogenic Na+ pump contributes
      minimally to the repolarization of Va in sea hare intestine. The origin of the
      hyperpolarization of Va resides therefore, at least in part, in the increase in
      GKa, which restores the driving force for Na(+)-alanine cotransport and prevents
      K+ accumulation in the enterocytes.

PMID- 7733389
TI  - Effect of loading right atrial and ventricular receptors on stimulated AVP, ACTH,
      and renin secretion in awake dogs.
AB  - The goal of this study was to test the hypothesis that increasing or decreasing
      the load on baroreceptors in the right heart influenced the secretion of arginine
      vasopressin (AVP), adrenocorticotropic hormone (ACTH), and renin during a state
      of sustained arterial hypotension. The hypothesis was tested in chronically
      instrumented conscious dogs prepared with inflatable cuffs around the pulmonary
      artery (PA) and the thoracic inferior vena cava (IVC). In one protocol (n = 5),
      mean arterial pressure was reduced 10 or 20% below control by constriction of the
      PA, a maneuver that caused a fall in left atrial pressure (LAP) and an increase
      in right atrial pressure (RAP). Plasma AVP, ACTH, atrial natriuretic peptide
      (ANP), and plasma renin activity (PRA) all increased (P < 0.05) in response to
      constriction of the PA. Reducing RAP to control by constriction of the IVC during
      maintained constriction of the PA had no effect on MAP, LAP, plasma AVP, ACTH, or
      PRA, but plasma ANP fell significantly. In a separate protocol (n = 4),
      constriction of the IVC was used to reduce MAP 10 or 20% below control, and this
      led to significant decreases in both LAP and RAP and increases in plasma AVP,
      ACTH, and PRA. RAP was then increased above control by constriction of the PA
      without altering either MAP or LAP. Raising RAP from a level that was 6.3 +/- 1.3
      mmHg below control to 3.5 +/- 1.0 mmHg above control had no effect on plasma AVP,
      ACTH, or PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733390
TI  - Effects of baroreceptor reflex on efferent pulmonary sympathetic nerve activity
      in anesthetized cat.
AB  - We analyzed the baroceptor reflex effect on efferent pulmonary sympathetic nerve
      activity (PSNA) in anesthetized cats. PSNA was recorded from the central end of
      the cut nerve bundle, which was isolated from the lobar artery supplying the
      diaphragmatic lobe. Renal sympathetic nerve activity (RSNA) and aortic blood
      pressure (AP) were also simultaneously measured. There were grouped discharges
      synchronous with cardiac cycle and its respiratory modulation in PSNA. In a given
      cardiac cycle, the discharge patterns differed between the pulmonary and renal
      nerves. Average sympathetic nerve activity and AP obtained from 100 consecutive
      cardiac cycles showed that the baroreceptor reflex delay time on the pulmonary
      nerve (266 ms) was longer than that on the renal nerve (195 ms). The data
      indicate nonuniformity in the cardiac-related PSNA and RSNA. The grouped PSNA
      disappeared with hexamethonium bromide, indicating that PSNA originates from
      postganglionic efferent fibers. To examine the baroreflex response of PSNA, AP
      was increased by 70 mmHg with phenylephrine and decreased by 70 mmHg with
      nitroprusside. PSNA changed inversely to the changes in mean aortic pressure
      (MAP). In the delta MAP-delta PSNA curve, delta PSNA reached the maximum level
      (74%) and the noise level at -56 +/- 4 and 58 +/- 4 mmHg, respectively. The mean
      slope of the curve was 1.5 +/- 0.1%/mmHg. RSNA also responded inversely to the
      MAP change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733391
TI  - Potassium's cardiovascular protective mechanisms.
AB  - High rates of potassium intake are associated with protection from cardiovascular
      diseases in populations consuming primitive diets and in vegetarians living in
      industrialized cultures. In studies in humans and in animals, a strong inverse
      association between potassium intake and hypertension and stroke has been
      described. However, acceptance of the putative protective effect has been limited
      by inadequate understanding of 1) long-term potassium regulation, and 2)
      mechanisms by which small changes in plasma potassium concentration may affect
      development of cardiovascular diseases. In this review, we present results from
      analyses of long-term potassium regulation that indicated 1) changes in potassium
      intake may result in potassium concentrations from 3.1 to 4.6 mmol/l, and 2) when
      the initial rate is below normal, potassium concentration is very sensitive to
      changes in potassium intake rate. In addition, we present results that provide
      bases for possible mechanisms by which potassium may protect against
      cardiovascular diseases: 1) increases in potassium inhibit free radical formation
      from vascular endothelial cells and macrophages; 2) elevation of potassium
      inhibits proliferation of vascular smooth muscle cells; 3) platelet aggregation
      and arterial thrombosis are inhibited by elevation of potassium; and 4) renal
      vascular resistance is reduced and glomerular filtration rate is increased by
      elevation of plasma potassium. We propose that elevation of dietary potassium
      intake increases plasma potassium concentration, thereby inhibiting free radical
      formation, smooth muscle proliferation, and thrombus formation. As a result, the
      rate of atherosclerotic lesion formation and thrombosis will be diminished. In
      addition, we propose the increase in glomerular filtration rate will cause a
      shift in the relationship between arterial pressure and sodium excretion that
      will lead to a reduction in arterial blood pressure. By these actions, high
      levels of dietary intake of potassium could provide the observed protection
      against the cardiovascular diseases that have plagued humankind since we began
      eating a modern high-sodium, low-potassium diet.

PMID- 7733392
TI  - The physiology of heat regulation.
AB  - Heat regulation is presented as the physiological method of handling metabolic
      heat, instead of temperature regulation. Experimental evidence of heat regulation
      from the literature is reviewed, including more than 20 years of calorimetric
      studies by the author. Changes in heat production are followed by slow
      exponential changes in heat loss, which produce changes in body heat storage.
      Heat balance occurs at many levels of heat production throughout the day and
      night, and at each level there is a related level of rectal temperature. Heat
      flow can be sensed by the transcutaneous temperature gradient. The controller for
      heat loss appears to operate like a servomechanism, with feedback from heat loss
      and possibly feedforward from heat production. Physiological responses defend the
      body heat content, but heat content varies over a range that is related to heat
      load. Changes in body heat content drive deep body temperatures.

PMID- 7733393
TI  - Chemoreceptor-sensitive neurons in commissural subnucleus of nucleus tractus
      solitarius of the rat.
AB  - Experiments were carried out in pentobarbital-anesthetized, vagotomized,
      paralyzed, and artificially ventilated male Wistar rats with a pneumothorax.
      Blood pressure, heart rate, and phrenic nerve activity were recorded.
      Extracellular neuronal recordings were made by glass micropipettes in a midline
      area in the commissural subnucleus of the nucleus tractus solitarius. At the end
      of the experiment, the recording sites were marked. Chemoreceptors were
      stimulated by tracheal administration of N2 or injection of CO2-saturated saline
      (50 microliters) near the carotid body. The baroreceptors were stimulated by an
      intravenous injection of phenylephrine (1-3 micrograms). Neurons that were
      excited by chemoreceptor stimulation but not baroreceptor stimulation were found
      in the commissural subnucleus of nucleus tractus solitarius and were designated
      as chemoreceptor-sensitive neurons. They exhibited a continuous discharge (9.9 +/
      1.3 spikes/s) that showed no apparent relation to either phrenic nerve bursts or
      arterial pulses. Such neurons were not found in the rostral portions of the
      nucleus tractus solitarius. These results confirm and extend our previous reports
      in which a discrete chemoreceptor projection site was identified in the
      commissural subnucleus of the rat.

PMID- 7733394
TI  - Baroreflex attenuation after hypotension induced by vena caval occlusion in
      anesthetized dogs.
AB  - We determined effects of vena caval occlusion-induced systemic hypotension of 50
      mmHg lasting 10 min (VCO) on efferent sympathetic nerve activity (SNA) and
      sympathetic baroreflex responsiveness. We recorded simultaneously SNA to the
      kidney (RNA), heart (CNA), spleen (SpNA), and liver (HNA) in anesthetized dogs.
      Baroreflex sensitivity was assessed using the ratio of a reflex SNA increase to a
      mean arterial pressure fall, which was also induced by caval occlusion. During
      VCO, SNA initially and equivocally increased, followed by recovery toward
      baseline. Cervical vagotomy attenuated the VCO-induced initial sympathoexcitation
      and subsequently maintained SNA at higher levels than those of intact animals, a
      finding basically similar to hemorrhagic hypotension [S. Koyama, F. Sawano, Y.
      Matsuda, Y. Saeki, T. Shibamoto, T. Hayashi, Jr., Y. Matsubayashi, and M.
      Kawamoto. Am. J. Physiol. 262 (Regulatory Integrative Comp. Physiol. 31): R579
      R585, 1992]. At 5 min after releasing VCO, the baroreflex responsiveness was
      significantly attenuated: RNA, 79 +/- 11%; CNA, 78 +/- 8%; HNA, 60 +/- 16%; SpNA,
      81 +/- 13% of the corresponding baseline. Fifteen minutes after VCO, this
      attenuation disappeared. Either vagotomy or pretreatment with intravenous
      vasopressin V1 receptor antagonist abolished this baroreflex attenuation. In
      conclusion, systemic hypotension to 50 mmHg for 10 min causes transient
      attenuation of sympathetic baroreflex sensitivity due to circulating vasopressin
      released by unloading of cardiopulmonary receptors during hypotension.

PMID- 7733395
TI  - Cortisol, ACTH, and cardiovascular response to a cognitive challenge paradigm in
      aging and depression.
AB  - Aging and hypercortisolism may be associated with alterations of stress-induced
      hormone release. We therefore studied 20 normal controls of two different age
      groups (< 30 and > 60 yr of age) and 20 age-matched patients with major
      depression; baseline ACTH and cortisol secretion (between 1400 and 1700) as well
      as blood pressure and heart rate and their responses to a 45-min lasting signal
      detection task (1705-1750) were determined. No difference in basal hypothalamic
      pituitary-adrenal (HPA) system activity between young and older healthy controls
      was noted. The cognitive challenge resulted in an increase in stress-induced
      hormonal secretion that was greater in the older controls than in their young
      counterparts. Basal hypercortisolemia and, at baseline, heart rates were higher
      in depressed patients, regardless of age. Blood pressure was elevated in older
      healthy controls as well as depressed patients. With the exception of the young
      depressed patients, all groups responded with an increase of the cardiovascular
      parameters during stress.

PMID- 7733396
TI  - Dissociation between food intake, diet composition, and metabolism in parabiotic
      partners of obese rats.
AB  - When one member of a parabiosed pair of rats is overfed, its ad libitum-fed
      partner loses body fat in the absence of a statistically significant decrease in
      food intake. Three experiments investigated the relationships between food
      intake, metabolism, and body composition in this model. In vivo measurement of
      lipogenesis confirmed that loss of fat is associated with decreased fat
      deposition. When partners of overfed rats were compared with food-restricted
      single rats, proportional changes in body composition and metabolism were similar
      for the two treatments, although there was no significant change in the food
      intake of parabiotic rats, whereas restricted rats received only 60% of the
      intake of their controls. The final experiment demonstrated that changes in body
      composition of partners of overfed rats were independent of dietary composition.
      These results suggest that, when a rat is made obese by overfeeding, a
      circulatory factor is released that inhibits fat deposition and disrupts
      regulatory mechanisms that normally stimulate food intake during a period of
      negative energy balance.

PMID- 7733397
TI  - Reduced lactate transport in denervated rat skeletal muscle.
AB  - The purpose of this study was to investigate the effect of the neural regulation
      of contractile activity on lactate transport in skeletal muscle. Contractile
      activity of the rat soleus muscle was abolished by denervating the hindlimb
      muscles in one leg (3 days) while the sham-operated contralateral hindlimb
      muscles served as a control. Three days after surgery, lactate transport into the
      soleus muscle was measured in vitro, using incubated soleus muscle strips.
      Lactate uptake by the denervated soleus muscle was reduced compared with control
      (P < 0.05). The diffusive component of lactate transport was unaltered by
      denervation (P > 0.05). These results translated into a reduction in lactate
      carrier-mediated transport capacity (-68%) in the denervated soleus (P < 0.05).
      These studies indicate that loss of contractile activity results in a decrement
      of lactate transport, which is probably due to a reduction in the number of
      lactate carriers in the sarcolemma. Our results suggest that the inherent
      activity of the muscle is important in maintaining the lactate transport system.

PMID- 7733398
TI  - Intracellular pH in lizards after hypercapnia.
AB  - We used the transmembrane distribution of 5,5-[2-14C]dimethyloxazolidine-2,4
      dione ([14C]DMO) and 31P magnetic resonance spectroscopy (NMR) to investigate the
      effects of hypercapnia on intracellular pH (pHi) in brain and skeletal muscle of
      two lizard species: Anolis equestris and Dipsosaurus dorsalis. In control animals
      (normocapnic), plasma PCO2 (3.3 +/- 0.1 kPa) and plasma pH (7.52 +/- 0.01) for D.
      dorsalis were not significantly different from the values for A. equestris (2.8
      +/- 0.2 kPa and 7.59 +/- 0.02, respectively). Furthermore 60 min of 5% CO2
      increased plasma PCO2 and decreased plasma pH by the same amounts in both
      species. Brain pHi values determined with the DMO method were not significantly
      different from values determined with NMR. Control values of brain pHi (DMO, 7.16
      +/- 0.01; NMR, 7.11 +/- 0.02) and muscle pHi were significantly higher for D.
      dorsalis (DMO, 7.15 +/- 0.03) than for A. equestris (DMO, 6.99 +/- 0.03; NMR,
      7.02 +/- 0.02 for brain; DMO, 6.97 +/- 0.03 for muscle). In addition, changes in
      tissue pHi after 60 min of 5% CO2 were significantly different for the two
      species. In D. dorsalis muscle and brain pHi decreased significantly after
      hypercapnia, whereas in A. equestris muscle pHi decreased significantly but brain
      pHi was unchanged. Our findings were independent of the methods used to determine
      pHi. The smaller change in brain and muscle pHi than in plasma pH for A.
      equestris is consistent with the view that pHi regulation involves active
      processes such as transmembrane ion transport.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733399
TI  - Role of epinephrine in TNF and IL-6 production from isolated perfused rat liver.
AB  - A bidirectional communication exists between the nervous system and the immune
      system. Evidence has accumulated suggesting that cytokines-immune peptides
      influence sympathetic neuronal survival and that cytokines can promote the
      secretion of catecholamines. Using an isolated perfused rat liver (IPRL)
      preparation, we have shown that the liver is an important source of circulating
      cytokines in response to lipopolysaccharide (LPS) and that corticosterone dose
      dependently influenced LPS-induced production of tumor necrosis factor (TNF) and
      interleukin-6 (IL-6). In this study, we investigated the direct effect of
      epinephrine (another stress hormone) on the production of TNF and IL-6 in liver.
      We demonstrated that epinephrine (1 microM/ml) alone did not induce TNF
      bioactivity but significantly increased IL-6 bioactivity from IPRL effluent. When
      the IPRL was infused with LPS, epinephrine significantly decreased TNF
      bioactivity. Epinephrine in LPS-treated livers also significantly increased IL-6
      bioactivity. Both responses were totally inhibited by the beta-blocker
      propranolol (10 microM/ml). Anisomycin, a protein synthesis inhibitor, infused
      into the IPRL completely blocked the rise in TNF and IL-6 concentrations in the
      effluent leaving the IPRL, supporting the hypothesis that the synthesis (or
      release) of these cytokines was dependent on protein synthesis. We then attempted
      to determine whether epinephrine exerts similar effects in vitro. Using isolated
      Kupffer cells and hepatocytes, we found that epinephrine alone had no effect on
      TNF and IL-6 production in Kupffer cells and hepatocytes but significantly
      decreased LPS-induced TNF bioactivity and increased LPS-induced IL-6 bioactivity
      in Kupffer cells. Our data support the hypothesis that epinephrine can promote IL
      6 secretion from IPRL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733400
TI  - Interleukin-1 increases splenic blood flow by affecting the sympathetic
      vasoconstrictor tonus.
AB  - The possibility that interleukin-1 (IL-1), a cytokine involved in immune and
      inflammatory mechanisms, can affect the blood flow of the spleen was considered
      because changes in spleen perfusion can affect immune cell recirculation,
      traffic, and homing. The results indicate that administration of a subpyrogenic
      dose of IL-1 induced a pronounced increase in splenic blood flow. This was not a
      general effect, because no change in blood flow of skeletal muscle was noticed.
      The studies also show that 1) the increase in splenic perfusion induced by IL-1
      is to a large extent independent from the secondary induction of nitric oxide
      (NO), 2) the splenic blood flow in the rat is under sympathetic control, and 3)
      the effect of IL-1 on splenic blood flow is completely abrogated after surgical
      interruption of the splenic nerve, which is predominantly composed of sympathetic
      fibers. It is concluded that the IL-1-mediated increase in splenic blood flow is
      most likely based on the inhibition of the sympathetic vasoconstrictor tonus in
      the rat spleen. These results show that a cytokine released by activated immune
      cells can regulate the blood flow of a main lymphoid organ, the spleen, by
      affecting mechanisms under neural control.

PMID- 7733401
TI  - Central inspiration increases barosensitivity of neurons in rat rostral
      ventrolateral medulla.
AB  - Barosensitive neurons in the rostral ventrolateral medulla (RVLM) often have a
      respiratory-related modulation of their activity. However, the extent of the
      interaction between baroreceptor and respiratory inputs is controversial. The
      main aim of the present study was to determine the effect of central respiratory
      drive (CRD) on the barosensitivity of RVLM neurons. Extracellular recordings were
      obtained from 68 barosensitive neurons in the RVLM of anesthetized, paralyzed,
      and bilaterally vagotomized Sprague-Dawley rats. Examination of phrenic-triggered
      histograms revealed five activity patterns among barosensitive neurons:
      inspiratory depression (type I, n = 20), early inspiratory activation (type II, n
      = 14), postinspiratory activation (type III, n = 18), expiratory depression (type
      IV, n = 5) and no modulation (type V, n = 11). In most neurons (types I and III
      and 56% of type II) inhibition produced by aortic nerve stimulation was greater
      in inspiration than in expiration. Cardiac-related modulation, as an index of
      natural phasic baroreceptor activation, was also greater in inspiration than
      expiration in type III neurons. The results demonstrate that CRD modulates the
      baroreflex at the level of the RVLM.

PMID- 7733402
TI  - Fever in pregnant, parturient, and lactating rats.
AB  - Conscious virgin, pregnant, or lactating rats were given intravenous Escherichia
      coli endotoxin while their temperatures were monitored telemetrically. Virgin
      females responded to 10-50 micrograms/kg endotoxin with a slight hypothermia,
      followed by a fever of nearly 2 degrees C magnitude. In pregnant rats given 25
      micrograms/kg of the endotoxin, fevers were reduced between 96 h before and 24 h
      after parturition compared with those seen in virgins or in lactating rats > 24 h
      postpartum. In the 24-h period before expected time of parturition, no rat
      developed a fever and the majority of animals became hypothermic; furthermore, in
      80% of such animals given 25 micrograms/kg endotoxin, the hypothermia was
      accompanied by death within 3-15 h. Some mortality and hypothermia were also seen
      up to 48 h before birth and up to 24 h after birth. No mortality was observed in
      virgin, pregnant, or lactating rats outside of this time period. We conclude
      that, around the time of delivery, there is a suppression of fever in the rat and
      occasional toxic responses to endotoxin.

PMID- 7733403
TI  - Hepatomesenteric release and removal of norepinephrine in swine.
AB  - Release and removal of norepinephrine (NE) by hepatomesenteric organs in
      anesthetized swine were examined using measurements of NE in arterial, portal,
      and hepatic venous plasma. NE spillover from the liver and mesenteric organs
      increased during splanchnic nerve stimulation, validating these measurements as
      indexes of sympathetic outflow. Administration of the neuronal uptake-blocking
      drug desipramine reduced mesenteric NE extraction more than hepatic extraction,
      suggesting that neuronal uptake was more important for NE removal in mesenteric
      organs than in the liver. Circulating NE was removed by the liver more
      efficiently than by mesenteric organs, whereas mesenteric NE spillover (2.46
      nmol/min) exceeded liver NE spillover (0.74 nmol/min). Hepatomesenteric NE
      spillover represented 53% of total body spillover; NE clearance was 42% of total
      body clearance. Because of efficient hepatic extraction of NE released by
      mesenteric organs, the sum of mesenteric and hepatic NE spillovers (3.20
      pmol/min) exceeded net hepatomesenteric spillover estimated using arterial and
      hepatic venous measurements alone (1.96 pmol/min). Thus valid assessment of the
      substantial amounts of NE released by hepatomesenteric organs requires separate
      examination of mesenteric and hepatic spillovers.

PMID- 7733404
TI  - Effects of age and gender on brown fat and skeletal muscle metabolic responses to
      cold in F344 rats.
AB  - Older male Fischer 344 (F344) rats do not maintain core temperature as well as do
      older females during cold exposure. To elucidate factors contributing to the
      decreased thermoregulatory ability of older males, the metabolic potentials of
      interscapular brown adipose tissue (IBAT) and skeletal muscle were evaluated at
      rest (26 degrees C) and during 4 h of cold (6 degrees C) in male and female F344
      rats, aged 6, 12, and 26 mo. Compared with 26-mo-old females, cold-exposed 26-mo
      old males exhibited a greater drop in core temperature and lower amounts of IBAT
      mitochondrial uncoupling protein (UCP) and IBAT thyroxine 5'-deiodinase (T5'D)
      activity. Unlike females, 26-mo-old males showed no cold-induced increase in
      total IBAT UCP or T5'D activity. In contrast, plasma norepinephrine was higher in
      cold-exposed 26-mo-old males vs. females, whereas plasma insulin and thyroxine
      did not differ with gender. Skeletal muscle oxidative capacity (measured by
      citrate synthase activity) and carbohydrate availability (measured by muscle
      glycogen and plasma glucose levels) did not differ between the 26-mo-old males
      and females. Our data suggest that altered regulation of IBAT UCP levels during
      cold exposure of aged rats, due at least in part to attenuated cold-induced IBAT
      T5'D activity, contributes to the gender difference in thermoregulatory ability
      of older males vs. females.

PMID- 7733405
TI  - Opioid growth factor modulates corneal epithelial outgrowth in tissue culture.
AB  - In addition to neuromodulation, endogenous opioid peptides serve as growth
      factors. To determine involvement of opioids in the homeostatic renewal and
      repair of the corneal epithelium, epithelial outgrowths from 3-mm explants of
      rabbit cornea were investigated. Blockade of opioid-receptor interaction by the
      potent opioid antagonist naltrexone (NTX) for 7 days significantly increased the
      extent of outgrowths and the number and labeling index (DNA synthesis) of
      epithelial cells, relative to control levels. Outgrowths exposed to the opioid
      growth factor (OGF) [Met5]enkephalin for 7 days were subnormal in extent and
      labeling index and displayed alterations in architectural pattern. The effects of
      OGF on epithelial outgrowth were blocked by concomitant exposure to the opioid
      antagonist naloxone; naloxone alone had no effect on growth at the concentration
      utilized. NTX and OGF were active in both serum-containing and serum-free
      cultures. Immunocytochemical investigations showed that both OGF and its opioid
      receptor zeta (zeta) were present in epithelial cells growing in control media.
      The results indicate that an endogenous opioid peptide and its receptor are
      present in mammalian corneal epithelium and serve to modulate cell proliferation,
      migration, and organization.

PMID- 7733406
TI  - Estradiol attenuates the antidiuretic action of vasopressin in ovariectomized
      rats.
AB  - To determine which ovarian hormone is involved in the sexually dimorphic
      antidiuretic action of vasopressin, the antidiuretic response to vasopressin was
      examined in sham-operated nonestrous female rats chronically treated with vehicle
      and in ovariectomized rats treated with vehicle, progesterone, estradiol, or the
      combination of estradiol and progesterone, respectively. Three-week-old female
      rats were sham operated or ovariectomized, and a slow-release hormone pellet was
      implanted at the 6th wk. The experiment was performed at the 10th to 12th wk in
      conscious, chronically instrumented rats hydrated with tap water (2% body wt).
      Infusion of vasopressin at rates of 10-1,000 pg.min-1.kg body wt-1 resulted in a
      dose-dependent antidiuretic response that was significantly enhanced in
      ovariectomized rats compared with the intact nonestrous females. Progesterone had
      no effect, whereas estradiol attenuated and restored the antidiuretic response to
      vasopressin to a level similar to that in intact nonestrous female rats. These
      results suggest that it is estrogen, but not progesterone, that reduces the
      antidiuretic response to vasopressin in the female rat.

PMID- 7733407
TI  - Inhibition of basal and reflex-mediated sympathetic activity in the RVLM by
      nitric oxide.
AB  - We examined possible functional roles for nitric oxide (NO) in the rostral
      ventrolateral medulla (RVLM), which is the final area for integration of
      sympathetic nerve activity (SNA) within the brain stem. Chloralose-anesthetized
      cats were completely baro- and chemoreceptor denervated, the RVLM was exposed for
      microinjections, and preganglionic SNA was recorded from the white ramus of the
      3rd thoracic segment. Injections of NG-nitro-L-arginine (L-NNA), an inhibitor of
      NO synthase, but not of NG-nitro-D-arginine, caused distinct increases in SNA and
      arterial blood pressure (BP). Excitatory somatosympathetic reflex amplitudes
      evoked by electrical stimulation of the 4th intercostal nerve were significantly
      increased by L-NNA whereas inhibitory responses to baroreflex activation by
      stimulation of the carotid sinus nerve were not affected. The effects of L-NNA
      were counteracted by the NO-donor compounds glyceryltrinitrate and S-nitroso-N
      acetylpenicillamine, which decreased BP and SNA below control values at higher
      doses. These results suggest that endogenous NO, in addition to its peripheral
      actions, modulates the central nervous control of cardiovascular functions by
      reduction of basal sympathetic tone and by attenuation of excitatory reflex
      responses.

PMID- 7733408
TI  - Fallacy of indexing renal and systemic hemodynamic measurements for body surface
      area.
AB  - Renal plasma flow, glomerular filtration rate, and cardiac output are
      traditionally indexed for body surface area by expressing these traits as per
      surface-area ratios. Indexing is intended to remove interindividual variation
      attributable to differences in body size. Regression is an alternative method
      commonly used to adjust other biological traits for the effects of a covariate,
      such as body surface area. The purpose of this study was to compare the indexing
      and regression methods of adjusting renal plasma flow, glomerular filtration
      rate, and cardiac output for interindividual differences in body surface area. We
      estimated renal plasma flow by the clearance of p-aminohippurate, glomerular
      filtration rate by clearance of inulin, and cardiac output by thoracic electrical
      impedance in a sample of 78 unrelated females and 78 unrelated males (ages 20
      49.9 yr) from the general population of Rochester, MN. The indexing method
      created negative dependencies of renal plasma flow and cardiac output on body
      surface area and failed to eliminate the positive dependency of glomerular
      filtration rate on body surface area. Moreover, indexing obscured differences in
      mean renal plasma flow between females and males and created differences in mean
      cardiac output between the genders. In contrast, the regression method
      consistently eliminated dependencies of each trait on body surface area and did
      not lead to inappropriate inferences about mean differences in these traits
      between females and males. We conclude that the indexing method of adjusting
      renal plasma flow, glomerular filtration rate, and cardiac output for
      interindividual differences in body surface area should be abandoned and replaced
      by use of the regression method.

PMID- 7733409
TI  - Circulating tumor necrosis factor-alpha does not mediate endotoxin-induced
      hypothermia in rats.
AB  - The present study was designed to investigate the role of macrophages and
      circulating tumor necrosis factor-alpha (TNF-alpha) in the endotoxin-induced
      hypothermic responses in rats. Intravenous as well as intraperitoneal
      administration of endotoxin to male Wistar rats (0.5 mg/kg) led to increased
      plasma TNF-alpha concentrations and a transient hypothermia, which reached its
      nadir after 90 min. The hypothermia and plasma TNF-alpha responses to endotoxin
      were abolished after elimination of peripheral macrophages. Seven days after the
      first challenge, tolerance of the hypothermic response was found if the same dose
      was administered intraperitoneally but not if it was administered intravenously.
      Tolerance of the TNF-alpha response was induced irrespective of the route of
      endotoxin administration. We hypothesize that, after intravenous administration
      of endotoxin, macrophage-dependent and -independent mechanisms are activated,
      whereas the hypothermic response to intraperitoneal endotoxin involves primarily
      macrophage-dependent mechanisms. These mechanisms may relate to the prime targets
      reached by endotoxin, such as macrophages and endothelial cells. Because the
      development of tolerance of the hypothermic response is dependent on the route of
      endotoxin administration, whereas that of the plasma TNF-alpha response is not,
      we conclude that circulating TNF-alpha is not the macrophage-derived cryogenic
      signal that triggers the hypothermic response.

PMID- 7733410
TI  - Effects of Ca2+ ionophore ionomycin on insulin-stimulated and basal glucose
      transport in muscle.
AB  - There is evidence that an increase in sarcoplasmic Ca2+ stimulates glucose
      transport in muscle. Recent studies have provided the apparently conflicting
      finding that a sustained increase in cytosolic Ca2+ has little effect on basal
      glucose transport but inhibits insulin-stimulated transport. This study was done
      to try to explain this discrepancy. Continuous exposure of rat epitrochlearis and
      soleus muscles to the Ca2+ ionophore ionomycin (2 microM) had no effect on basal
      2-deoxyglucose (2-DG) transport but blunted, by approximately 40%, stimulation of
      2-DG transport by insulin. Decreasing Ca2+ in the medium to a very low level
      prevented this inhibition. Ionomycin induced a small increase in adenosine 3',5'
      cyclic monophosphate (cAMP); however, studies with the protein kinase A (PKA)
      inhibitor HA-1004 provided evidence that activation of PKA by cAMP does not
      mediate the inhibition of glucose transport. When muscles were allowed to recover
      in the absence of ionomycin for 15 min, basal 2-DG transport was significantly
      increased. Our results agree with previous studies showing that a sustained
      influx of Ca2+ into the cytoplasm can inhibit insulin-stimulated glucose
      transport. They further show that stimulation of glucose transport by Ca2+ is
      also inhibited. A recovery period that allows this inhibition to wear off unmasks
      the stimulation of glucose transport by an increase in sarcoplasmic Ca2+.

PMID- 7733411
TI  - Part-set cuing in incidental and implicit memory.
AB  - We report inhibitory effects of part-set cuing in an incidental memory task. Even
      when subjects did not expect a memory test during study, re-presentation of some
      of the study words (Experiments 1 and 2) or presentation of related words
      (Experiment 3) during test inhibited memory performance. Also, in Experiment 3,
      inhibitory effects of part-set cuing emerged when subjects were completing
      fragments of the studied words, but only when they were explicitly trying to
      remember those words from the list. There was a facilitatory effect of part-set
      cuing when subjects were simply completing the fragments with the first words
      they could think of. These results suggest that the part-set cuing effect is
      largely independent of what happens during the study phase and dependent on a
      deliberate effort to remember during the test phase.

PMID- 7733412
TI  - Donald E. Broadbent: 1926-1993.

PMID- 7733413
TI  - Memory styles and related abilities in presentation of self.
AB  - The notion of a person's memory style (elaborated in Sehulster, 1988) was
      investigated as it relates to the presentation of self. A memory style is defined
      as a combination of a subject's (perceived) ability in verbal memory, auto-
      biographical memory, and prospective memory, as measured by the Memory Scale
      (Sehulster, 1981b). In addition to filling out the Memory Scale, 325 subjects
      completed a 72-item questionnaire that tapped descriptions of abilities and
      experiences. The range of abilities and experiences was drawn loosely from
      Gardner's (1985) notion of multiple intelligences. Distinct patterns of self
      report were observed for different memory styles. For instance, a love of
      listening to music was associated with the memory style that is high in both
      verbal and autobiographical memory but low in prospective memory; a love for
      numbers and mathematics was associated with the memory style that is high in both
      verbal and prospective memory but low in autobiographical memory. The results
      suggest broad individual differences in information processing. Gender
      differences are discussed in relation to memory styles.

PMID- 7733415
TI  - The hazards of epidemiology.

PMID- 7733414
TI  - Children's associative learning: automatic and deliberate encoding of meaningful
      associations.
AB  - Three experiments were conducted examining 10- and 11-year-old children's
      deliberate and automatic encoding of meaningful associative relationships on a
      paired-associate learning task. Subjects in Experiment 1 were presented pairs of
      related and unrelated words under deliberate memorization and item-specific
      incidental-learning conditions. Cued-recall performance was superior with related
      relative to unrelated pairs under both instructional conditions, suggesting that
      the encoding of an association between items occurred automatically with
      meaningfully related words. In Experiment 2, it was found that execution of a
      verbal elaboration strategy required more time with unrelated than with related
      pairs, suggesting greater ease of elaboration strategy execution with related
      materials. Experiment 3 monitored strategy use online using a think-aloud
      procedure. Cued-recall performance was superior with related pairs when subjects
      used rehearsal. In contrast, elaboration produced equivalent levels of recall
      with both types of items, but subjects executed the strategy successfully more
      often with related than with unrelated pairs. These findings are discussed in
      terms of the role of automatic processes and the effort demands of strategy
      execution in children's strategy use.

PMID- 7733416
TI  - Annotation: the National Academy of Sciences-National Research Council Twin
      Registry.

PMID- 7733417
TI  - Annotation: cause and noncause--nutritional epidemiology and public health
      nutrition.

PMID- 7733418
TI  - Topics for our times: life in a refugee camp--lessons from Cambodia and site 2.

PMID- 7733419
TI  - The new paradigm of public health nutrition.

PMID- 7733420
TI  - Racial/ethnic differences in the likelihood of cesarean delivery, California.
AB  - OBJECTIVES: The purpose of this study was to determine whether women's
      sociodemographic characteristics are independently associated with cesarean
      delivery. METHODS: A retrospective review was conducted of hospital discharge
      data for singleton first births in California in 1991. RESULTS: After insurance
      and personal, community, medical, and hospital characteristics had been
      controlled, Blacks were 24% more likely to undergo cesarean delivery than Whites;
      only among low-birthweight and county hospital births were Blacks not at a
      significantly elevated risk. Among women who resided in substantially non-English
      speaking communities, who delivered high-birthweight babies, or who gave birth at
      for-profit hospitals, cesarean delivery appeared to be more likely among non
      Whites and was over 40% more likely among Blacks than among Whites. CONCLUSIONS:
      The findings cannot establish causation, but the significant racial/ethnic
      disparities in delivery mode, despite adjustment for social, economic, medical,
      and hospital factors, suggest inappropriate influences on clinical decision
      making that would not be addressed by changes in reimbursement. If practice
      variations among providers are involved, de facto racial differences in access to
      optimal care may be indicated. The role of provider and patient attitudes and
      expectations in the observed racial/ethnic differentials should also be explored.

PMID- 7733421
TI  - Reducing postneonatal mortality in West Virginia: a statewide intervention
      program targeting risk identified at and after birth.
AB  - OBJECTIVES: Excessive postneonatal mortality in West Virginia has been associated
      with inadequate health care. This paper describes two interventions aimed at
      those infants at greatest risk of dying. METHODS: Two systems of risk-related
      intervention were simultaneously introduced and funded statewide from 1985
      through 1987. Risk status was determined by a multifactorial score at birth or
      clinical risk factors later. At-risk infants were linked with physicians who
      provided specified care plans. All infants were followed for 1 year for
      mortality. RESULTS: Of 4570 infants with a high Sheffield Birth Score, 45%,
      together with 1003 infants with clinical risk factors, received specified care
      plans. High-risk infants constituted 7.6% of total resident births. Odds ratios
      for overall postneonatal mortality and sudden infant death syndrome in high-birth
      score infants compared with low-birth-score infants were 6.2 (95% confidence
      interval [CI] = 4.2, 9.3) and 11.2 (95% CI = 5.4, 23.2), respectively. The
      relative risks of postneonatal mortality were similarly significant for infants
      with most clinical risk factors. During the program there was a 21.4% reduction
      in the trend of yearly standardized mortality ratios, which differed markedly
      from the trend in surrounding states. The data suggest that 33 lives were saved
      at a cost of $36,363 per infant. CONCLUSION: Ensuring affordable, available,
      accessible, and acceptable care for a small group of at-risk infants was
      associated with a dramatic drop in overall postneonatal mortality in West
      Virginia.

PMID- 7733422
TI  - Return rates and outcomes from ethnicity-specific mental health programs in Los
      Angeles.
AB  - OBJECTIVES: The present study compared the return rate, length of treatment, and
      treatment outcome of ethnic minority adults who received services from ethnicity
      specific or mainstream programs. METHODS: The sample consisted of 1516 African
      Americans, 1888 Asian Americans, and 1306 Mexican Americans who used 1 of 36
      predominantly White (mainstream) or 18 ethnicity-specific mental health centers
      in Los Angeles County over a 6-year period. Predictor variables included type of
      program (ethnicity specific vs mainstream), disorder, ethnic match (whether or
      not clients had a therapist of the same ethnicity), gender, age, and Medi-Cal
      eligibility. The criterion variables were return after one session, total number
      of sessions, and treatment outcome. RESULTS: The study indicated that ethnic
      clients who attended ethnicity-specific programs had a higher return rate and
      stayed in the treatment longer than those using mainstream services. The data
      analyses were less clear cut when treatment outcome was examined. CONCLUSIONS:
      The findings support the notion that ethnicity-specific programs seem to increase
      the continued use of mental health services among ethnic minority groups.

PMID- 7733423
TI  - Vasectomy in the United States, 1991.
AB  - OBJECTIVES: Recent conflicting findings on possible health risks related to
      vasectomy have underscored the need for reliable and representative estimates of
      numbers and rates of vasectomies in the United States. The purpose of this study
      was to estimate the annual US number, rate, and characteristics of vasectomies in
      1991. METHODS: A national survey of urology, general surgery, and family practice
      physician practices was conducted with probability sampling methods (n = 1685
      physicians). RESULTS: An estimated 493,487 (95% confidence interval = 450,480,
      536,494) vasectomies were performed in 1991, for a rate of 10.3 procedures per
      1000 men aged 25 through 49 years. Most vasectomies were performed by urologists,
      and most were done in physicians' offices with local anesthesia and ligation as
      the method of occlusion. The rate of vasectomies was highest in the Midwest.
      CONCLUSIONS: This survey provides the first national estimates of the number and
      rate of vasectomies in the United States, as well as the first estimates of
      occlusion method used. Results confirm previous findings that urologists perform
      most vasectomies and that most vasectomies are performed with local anesthesia.
      Recommendations include the monitoring of vasectomy numbers and rates as well as
      demographic studies of men obtaining vasectomies.

PMID- 7733424
TI  - The costs and effects of a nutritional education program following work-site
      cholesterol screening.
AB  - OBJECTIVES: The purpose of this study was to assess the costs and impact of a
      nutrition education program following a cholesterol screening. METHODS: Forty
      work-sites were randomly assigned to one of two educational interventions: a
      "usual" intervention of 5 minutes of counseling, or a "special" intervention of 2
      hours of behaviorally based education on dietary changes to lower serum
      cholesterol. Costs were monitored, and cholesterol levels were retested 6 and 12
      months later. RESULTS: The total per-person cost for screening and the
      educational intervention was about $50. Cholesterol levels differed little
      between the two intervention groups 6 months after screening, but after 12 months
      those in the special intervention worksites showed a 6.5% drop in cholesterol,
      whereas those at the usual intervention worksites showed a drop of only 3.0%.
      Hence a 3.5% cholesterol reduction was attributable to the special intervention.
      CONCLUSIONS: A behaviorally based nutrition education program following
      cholesterol screening can have a meaningful impact on long-term cholesterol
      levels at a low cost. Nutrition education in work-sites may therefore be a useful
      way to lower the risk of heart disease in communities.

PMID- 7733425
TI  - An outbreak of hypervitaminosis D associated with the overfortification of milk
      from a home-delivery dairy.
AB  - OBJECTIVES: The purpose of the study was to identify cases of hypervitaminosis D
      caused by the inadvertent overfortification of milk from a home-delivery dairy
      and to identify risk factors for this illness. METHODS: Hospital discharge,
      laboratory, and state health department data were used to define, identify, and
      describe cases of hypervitaminosis D diagnosed in the exposed communities between
      January 1, 1985, and June 30, 1991. To identify disease risk factors, community
      based sex- and age-matched controls were used in a case-control study. RESULTS:
      Of the 56 case patients identified, at least 41 were hospitalized; 2 died. The
      study included 33 case patients and 93 control subjects. Nineteen of the 33 case
      patients had been customers of the implicated dairy. Risk of illness rose with
      increasing consumption of the dairy's milk and was also associated with vitamin D
      supplement use, sunburn susceptibility, and cancer history. Accounting for these
      factors did not alter the association between drinking the dairy's milk and
      developing hypervitaminosis D. CONCLUSIONS: Overfortification of milk with
      vitamin D can lead to hypervitaminosis D, manifested by severe illness and death.
      The episode highlights the need for monitoring the fortification process and
      enforcing the upper limit for vitamin D addition to milk.

PMID- 7733426
TI  - Evaluating food fortification options: general principles revisited with folic
      acid.
AB  - OBJECTIVES: This article uses folic acid as an example to illustrate some of the
      complex issues and general principles that emerge when evaluating fortification
      of the food supply as one possible means to address a public health
      recommendation. METHODS: Distributions of current daily folate intakes from
      conventional foods and dietary supplements were estimated. Intakes that might
      result from fortification of cereal-grain products and ready-to-eat cereals at
      various levels for eight age-gender groups were also estimated by using the US
      Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey.
      RESULTS: The results illustrate that fortification of the US food supply tends to
      increase folate intakes of consumers at the high end of the intake distribution
      curves in the general population to a greater extent than it affects consumers at
      the low end of the intake distribution curves in the target population.
      CONCLUSIONS: The effectiveness of food fortification options for a target
      population and the safety for the general population impose conflicting
      challenges that must be considered concurrently when making decisions about
      fortifying the US food supply.

PMID- 7733427
TI  - Folic acid fortification of grain: an economic analysis.
AB  - OBJECTIVES: The purpose of this study was to compare the economic costs and
      benefits of fortifying grain with folic acid to prevent neural tube defects.
      METHODS: A cost-benefit analysis based on the US population, using the human
      capital approach to estimate the costs associated with preventable neural tube
      defects, was conducted. RESULTS: Under a range of assumptions about discount
      rates, baseline folate intake, the effectiveness of folate in preventing neural
      tube defects, the threshold dose that minimizes risk, and the cost of
      surveillance, fortification would likely yield a net economic benefit. The best
      estimate of this benefit is $94 million with low-level (140 micrograms [mcg] per
      100 g grain) fortification and $252 million with high-level (350 mcg/100 g)
      fortification. The benefit-to-cost ratio is estimated at 4.3:1 for low-level and
      6.1:1 for high-level fortification. CONCLUSIONS: By averting costly birth
      defects, folic acid fortification of grain in the United States may yield a
      substantial economic benefit. We may have underestimated net benefits because of
      unmeasured costs of neural tube defects and unmeasured benefits of higher folate
      intake. We may have overestimated net benefits if the cost of neurologic sequelae
      related to delayed diagnosis of vitamin B12 deficiency exceeds our projection.

PMID- 7733428
TI  - Predictors of dietary intake in a functionally dependent elderly population in
      the community.
AB  - OBJECTIVES: The aim of this study was to describe dietary intake and identify
      predictors of energy and protein intake in a group of high-risk elderly people.
      METHODS: All elderly persons receiving publicly financed home care services in
      the area of Sherbrooke, Quebec, Canada, were eligible. Subjects (n = 145) 60 to
      94 years of age from three home care programs were interviewed to measure
      sociodemographic, health, and food-related behavior variables. Three
      nonconsecutive 24-hour recalls were used to describe usual dietary intake.
      Independent predictors of energy and protein intake were derived from multiple
      regression analyses. RESULTS: Very low mean energy intakes were observed in this
      functionally dependent population. More than 50% of the study subjects did not
      meet the recommended levels of daily protein intake (0.8 g/kg body weight).
      Significant independent determinants of intake were burden of disease, stress,
      poor appetite, and vision. CONCLUSIONS: Results suggest that community-living
      elderly people with loss of autonomy may have more nutritional problems than
      healthy elderly individuals. Surveillance of predictors of dietary intake may
      enable early detection and prevention of nutritional deficits.

PMID- 7733429
TI  - Macronutrient intakes among adult Hispanics: a comparison of Mexican Americans,
      Cuban Americans, and mainland Puerto Ricans.
AB  - OBJECTIVES: The purpose of this study was to compare energy and macronutrient
      intakes between adult Mexican Americans, Cuban Americans, mainland Puerto Ricans,
      and non-Hispanics. METHODS: Age-specific mean intakes were estimated based on 24
      hour recalls from the Hispanic Health and Nutrition Examination Survey (HHANES)
      (1982 to 1984) and the Second National Health and Nutrition Examination Survey
      (NHANES II) (1976 to 1980) and were compared with the use of t tests. RESULTS:
      Mexican Americans had higher total fat, saturated fat, and monounsaturated fat
      intakes than did Puerto Ricans and older Cuban Americans. Cuban Americans and
      Puerto Ricans had similar intakes, except for younger Cuban Americans, who had
      higher total and saturated fat and lower carbohydrate intakes. Cholesterol
      intakes among Mexican American men and 60- to 74-year-old women were higher than
      those among other Hispanic groups. Carbohydrate and protein intakes were higher
      among Hispanic groups compared with those among non-Hispanics while total fat
      intakes were generally lower. CONCLUSIONS: Since macronutrient intakes differ
      between Hispanic groups, dietary research, recommendations, and interventions
      should be targeted to each group individually. Older Puerto Rican and Cuban
      American adults met population guidelines for reducing chronic disease risk for
      more macronutrients than any other group.

PMID- 7733430
TI  - Body weight patterns among the Chinese: results from the 1989 and 1991 China
      Health and Nutrition Surveys.
AB  - OBJECTIVES: A longitudinal survey assessed the distribution of adult body weight
      among the Chinese population. METHODS: Data from the 1989 and 1991 China Health
      and Nutrition Survey were used to study changes in the proportions of adults aged
      20-45 years who were classified as underweight, normal weight, overweight, and
      severely overweight. RESULTS: There was a slight decline in the proportion of men
      and women classified as underweight, but among lower-income persons an increase
      occurred. The proportion of adults with normal body weight decreased, and the
      proportions of those classified as overweight and severely overweight increased
      during the same period. The observed increases in proportions of adults
      classified as overweight and severely overweight were largely confined to the
      urban residents and to those in the middle- and high-income groups. CONCLUSIONS:
      Results indicate increases in both obesity and undernutrition. Current efforts in
      China to develop a preventive health care policy emphasize the prevention of
      excess nutrient intakes and overnutrition and, hence, address the problem of the
      increase in obesity among well-to-do, mostly urban residents. However, the
      increase in undernutrition among low-income Chinese adults should not be
      overlooked and requires further research and serious policy consideration.

PMID- 7733432
TI  - Chronic obstructive pulmonary disease in lifelong nonsmokers: results from
      NHANES.
AB  - The prevalence of chronic obstructive pulmonary disease was evaluated in 12,980
      lifelong nonsmoking adults who participated in one of three National US Health
      and Nutrition Examination Surveys. Also evaluated were the relationships between
      chronic obstructive pulmonary disease and age, sex, ethnicity, education, income,
      and certain environmental and occupational factors. Overall, 4% of men and 5% of
      women reported physician-diagnosed chronic obstructive pulmonary disease.
      Prevalence increased with age and with decreasing household income, was higher in
      Whites than in non-Whites, and was particularly high in Hispanic women. Further
      research is needed to explain the excess risk for chronic obstructive pulmonary
      disease in economically disadvantaged nonsmokers, and to assess the role of
      environmental tobacco smoke in nonsmokers' risk for the disease.

PMID- 7733431
TI  - Frequent dieting among adolescents: psychosocial and health behavior correlates.
AB  - OBJECTIVES: The present study examined correlates of frequent dieting in 33,393
      adolescents. It was hypothesized that frequent dieting would be correlated with
      negative psychosocial and health behavior outcomes. METHODS: A comprehensive,
      school-based health behavior survey was administered in 1987 to public school
      students in grades 7 through 12 in Minnesota. Students self-reported dieting
      behavior; substance use; suicidal, sexual, and delinquent behavior; family and
      peer concerns; sick days; and abuse history. Differences on psychosocial and
      health behavior risk factors by dieting frequency and by purging status were
      assessed with multivariate logistic regression, with body mass index and
      demographic variables controlled. RESULTS: Dieting frequency was associated with
      history of binge eating (females: odds ratio [OR] = 1.46, males: OR = 1.53); poor
      body image (females: OR = 0.56, males: OR = 0.63); lower connectedness to others
      (females: OR = 0.79); greater alcohol use (females: OR = 1.17); and greater
      tobacco use (females: OR = 1.08). Purging status was independently associated
      with negative risk factors in both males and females. CONCLUSIONS: These findings
      suggest that frequent dieting efforts in adolescents should not be viewed in
      isolation, but rather in the broader context of health and risk-taking behaviors.

PMID- 7733433
TI  - The epidemiology of walking for exercise: implications for promoting activity
      among sedentary groups.
AB  - The relative contribution of walking to overall leisure-time physical activity
      participation rates was studied among respondents from the 45 states that
      participated in the 1990 Behavioral Risk Factor Surveillance System (n = 81,557).
      The percentages of low income, unemployed, and obese persons who engaged in
      leisure-time physical activity (range = 51.1% to 57.7%) were substantially lower
      than the percentage among the total adult population (70.3%). In contrast, the
      prevalence of walking for exercise among these sedentary groups (range = 32.5% to
      35.9%) was similar to that among the total population (35.6%). Walking appears to
      be an acceptable, accessible exercise activity, especially among population
      subgroups with a low prevalence of leisure-time physical activity.

PMID- 7733434
TI  - Young maternal age and congenital malformations: a population-based study.
AB  - This study examined the prevalence of congenital malformations across the
      maternal age spectrum and identified specific malformation types that contributed
      to the overall prevalence among mothers under the age of 20 years. Data were
      derived from the California Birth Defects Monitoring Program for 1983 through
      1988 live births. The distribution of prevalences of all nonchromosomal
      malformations was U-shaped across maternal age. Furthermore, several specific
      malformation types, representing nearly every organ system, were elevated among
      the infants of women under 20 years of age in comparison with those of women 25
      to 29 years old.

PMID- 7733435
TI  - Women dieters of normal weight: their motives, goals, and risks.
AB  - Using data from a national survey of weight loss practices, this study examined
      those dieters who were of normal weight. Forty-seven percent of White women, 25%
      of Black women, and 16% of men currently trying to lose weight had a body mass
      index under 25. Women's primary motive was health improvement. Among normal
      weight female dieters, 12% of Whites and 27% of Blacks were using risky
      strategies. Dieters were less likely than nondieters to smoke and reported better
      nutritional practices; however, they were not more likely to exercise, and their
      maximum weight fluctuation was 50% greater. Additional research on the
      consequences of dieting among normal-weight individuals is of high priority.

PMID- 7733436
TI  - Vitamin A capsule supplementation in Malawi villages: missed opportunities and
      possible interventions.
AB  - A population-based survey was used to assess childhood and maternal vitamin A
      capsule coverage in Malawi and to investigate missed opportunities for capsule
      distribution. Overall, 9.3% of children had received vitamin A supplementation in
      the previous 6 months. Missed opportunities for receiving vitamin A were high in
      younger children. Fifty-five percent of mothers were covered in 8 villages served
      by volunteers and 23% in the 58 villages without volunteers. Existing strategies
      need to be redesigned and new strategies defined. For instance, mothers could
      receive supplementation during infant BCG vaccination, and children could receive
      initial supplementation during measles vaccination. Village health volunteers
      could be used to target children over 2 years of age.

PMID- 7733437
TI  - Weight concerns and change in smoking behavior over two years in a working
      population.
AB  - The hypothesis that weight concerns are related to less successful smoking
      cessation and greater relapse among ex-smokers was prospectively evaluated. A
      population-based sample of 4981 working women and men 17 to 71 years of age was
      surveyed at 32 work sites. Current and previous weight loss efforts and smoking
      behavior were self-reported at baseline and 2 years later. Dieting and weight
      concerns were unrelated to smoking cessation or relapse. However, female smokers
      who had previously participated in a formal weight control program were three
      times more likely to quit smoking than those without a history of participation
      (25% vs 11%; odds ratio = 3.25, 95% confidence interval = 1.86, 5.67). Weight
      concerns and dieting efforts do not appear to inhibit smoking cessation or
      increase relapse in adults.

PMID- 7733438
TI  - Physician recommendations for dietary change: their prevalence and impact in a
      population-based sample.
AB  - A random-digit-dialing survey to examine the prevalence, content, and impact of
      physician dietary recommendations in a representative population-based sample of
      Washington State residents was administered to 1972 persons aged 18 years and
      older. Twenty percent of those surveyed received a physician's recommendation for
      dietary change in the previous year. The most common recommendations were to
      decrease intake of cholesterol, calories, and red meat and to increase intake of
      vegetables and fiber. Respondents receiving recommendations were more likely to
      report decreased use of high-fat foods and increased use of high-fiber foods and
      to be in the maintenance stage of dietary change. Results suggest that physicians
      can play a limited role in promoting dietary change.

PMID- 7733439
TI  - Predicting body fatness: the body mass index vs estimation by bioelectrical
      impedance.
AB  - The body mass index (weight in kilograms/height in square meters) is a common
      surrogate for fatness. With the advent of bioelectrical impedance analysis, more
      precise measurement of fatness in populations is now possible. We measured
      height, weight, and percentage that is fat by bioelectrical impedance analysis in
      2032 adults, ages 31 to 92, participating in the Framingham studies. Body mass
      index was a poor predictor of fatness in women (R2 = 0.55) and men (R2 = 0.38),
      and was imprecise (standard error of estimate = 5 percentage points). The
      relationship between percentage fat and body mass index was quadratic in both
      sexes, and was altered by age in women (P < .0001) and, to a lesser extent, in
      men (P < .027). These data suggest that body mass index is an imprecise
      measurement of fatness compared with bioelectrical impedance.

PMID- 7733440
TI  - Does WIC participation improve breast-feeding practices?
AB  - The effects of the Special Supplemental Nutrition Program for Women, Infants, and
      Children (WIC) on breast-feeding behavior have been sometimes found inadequate.
      The determinants of breast-feeding initiation and duration among WIC participants
      and nonparticipants were modeled by using retrospective cross-sectional data from
      the 1988 National Maternal and Infant Health Survey. This study corrects for self
      selection bias as far as the data allow, in addition to controlling for parents'
      ages, education, race, and family income. Findings suggest that prenatal WIC
      participation, combined with breast-feeding advice, significantly increases the
      initiation of breast-feeding but does not affect duration. The exact nature of
      effective breast-feeding advice given prenatally at WIC clinics is unclear and
      warrants further research.

PMID- 7733441
TI  - Combatting iodine deficiency: the iodization of water in the Central African
      Republic.

PMID- 7733442
TI  - The standardization of statewide hospitalized injury morbidity reports.

PMID- 7733443
TI  - Cytomegalovirus infection as a cause of hearing loss among children.

PMID- 7733444
TI  - Lady beetles and public health research: geographic and population scales.

PMID- 7733445
TI  - Female condom use among injection drug- and crack cocaine-using women.

PMID- 7733446
TI  - Priorities for vaginal microbicide research.

PMID- 7733447
TI  - Politics and public health research: HIV prevention policy in the schools.

PMID- 7733448
TI  - Quantitative analysis of conformational equilibrium using capillary
      electrophoresis: applications to protein folding.

PMID- 7733449
TI  - Assay of arginine-specific adenosine-5'-diphosphate-ribosyltransferase by
      capillary electrophoresis.
AB  - Using high-voltage capillary electrophoresis we detected ADP-ribosylarginine, a
      product of ADP-ribosylation reaction catalyzed by arginine-specific ADP
      ribosyltransferase in the presence of NAD and L-arginine. The authentic ADP
      ribosylarginine, detected by its ultraviolet absorbance at 254 nm, had a
      different retention time from NAD or nicotinamide. When the ADP-ribosylation
      reaction products were analyzed, the peak corresponding to ADP-ribosylarginine
      increased with incubation time and in an enzyme-dose-dependent manner. The lower
      limit of detection was 0.3 pmol, a value 100 times lower than that obtained with
      the reversed-phase high-performance liquid chromatography assay described
      previously. Using the capillary electrophoresis system, a thiol-independent ADP
      ribosyltransferase activity was detected in chicken spleen cell membrane. Since
      the capillary electrophoresis assay for ADP-ribosylarginine is simpler, faster,
      and less expensive than the high-performance liquid chromatography assay,
      determination of arginine-specific ADP-ribosyltransferase activity in animal
      tissues will be facilitated.

PMID- 7733450
TI  - An improved assay method for the measurement and detection of sphingomyelinase
      activity.
AB  - We have developed an improved assay method to measure sphingomyelinase activity
      and to detect this enzyme separated on polyacrylamide gels. The assay of
      sphingomyelinase activity involved immobilizing [N-methyl-14C]sphingomyelin on
      polyvinyldiflouride (PVDF) membrane, incubation with sphingomyelinase, and the
      measurement of radioactivity associated with [14C]phosphocholine. The enzyme
      activity was dependent on the concentration of sphingomyelin, enzyme, pH, and
      temperature. Thirty minutes of incubation time was optimal for enzyme activity.
      This enzyme had a bimodal pH optima, in that optimum enzyme activity was measured
      at pH 5.4 and 7.4. The detection of sphingomyelinase was pursued by separating
      the enzyme on a polyacrylamide gel and carrying out the enzyme assay by exposure
      to [14C]sphingomyelin blotted on a PVDF membrane. The enzyme activity on the PVDF
      membrane was visualized by autoradiography. A white band (depicting hydrolytic
      removal of [14C]sphingomyelin from PVDF was observed. Our method of detecting
      sphingomyelinase by immobilizing sphingomyelin on PVDF membrane may serve as a
      prototype for assaying various other enzymes in which the hydrolytic product is
      released into the aqueous phase. Moreover, our method for detecting
      sphingomyelinase on polyacrylamide gels may be helpful in further studies on the
      molecular biochemistry of this and related phospholipases.

PMID- 7733451
TI  - Sample pretreatment with nitrate reductase and glucose-6-phosphate dehydrogenase
      quantitatively reduces nitrate while avoiding interference by NADP+ when the
      Griess reaction is used to assay for nitrite.
AB  - An assay for the simultaneous measurement of nitrite and nitrate, products of
      nitric oxide metabolism, is described. Others have reported pretreating sample by
      using nitrate reductase (NR) and NADPH to reduce endogenous NO3- before assaying
      the resultant NO2- using the Griess reaction. However, we found that the NADP+
      formed during pretreatment interfered with the Griess reaction when NADPH was
      used at concentrations necessary to drive the NR reaction. For instance, 500
      microM NADP+ in 100 microM NaNO3- (without NR) causes a 90% interference with the
      formation of Griess reaction product. To limit interference, we modified the
      method by decreasing the NADPH concentration to 1 microM. NADPH was regenerated
      by coupling the NR reaction with that catalyzed by glucose-6-phosphate
      dehydrogenase (GD). Using this method, NaNO3- standard curves were linear up to
      100 microM and coincided with control curves obtained using NaNO2- incubated in
      parallel. Addition of urine up to a strength of 20% did not interfere with the
      assay. Comparison with an alternative assay based on cadmium reduction resulted
      in the following linear regression: [Cd method] = 0.915*[NR-GD method] + 0.37, r2
      = 0.997. Coupling GD to NR to recycle NADPH allows this cofactor to be used at a
      low concentration so that interference with the Griess reaction is negligible.

PMID- 7733452
TI  - Identification of derivatized peptides without radiolabels: tandem mass
      spectrometric localization of the tagged active-site nucleophiles of two
      cellulases and a beta-glucosidase.
AB  - A new method that uses nonradioactive active site-directed enzyme inactivators
      and high-performance liquid chromatography-electrospray ionization tandem mass
      spectrometry (HPLC-ESIMS/MS) to identify labeled peptides in a proteolytic digest
      is described. This method relies upon the fragmentation of labeled peptides in a
      predictable and reproducible manner in the collision cell of a tandem mass
      spectrometer. The exoglycanase from Cellulomonas fimi, endoglucanase C from
      Clostridium thermocellum, and the beta-glucosidase from Agrobacterium faecalis
      were labeled using 2-deoxy-2-halo-beta-glycosides, digested with pepsin, and
      subjected to HPLC-ESIMS/MS analysis, scanning in the neutral loss mode. Under
      these conditions only peptides that lose the (known) mass of the label are
      detected. Preliminary identification of candidate peptides can be achieved from
      the mass measured, in combination with the known sequence of the protein. Peptide
      identity can be confirmed through subsequent sequencing, either via further
      tandem MS experiments or via the Edman degradation. In all cases the peptides
      identified in this manner were consistent with those identified by the standard
      radioactive method. This mass spectrometric method represents a rapid,
      nonradioisotopic solution to the problem of identifying a modified peptide in a
      complex mixture. The technique is also sensitive, requiring only picomole amounts
      of protein.

PMID- 7733453
TI  - Evaluation of the efficacy of zwitterionic dodecyl carboxybetaine surfactants for
      the extraction and the separation of mycoplasma membrane protein antigens.
AB  - The ability to extract mycoplasma membrane protein antigens using the alkyl
      carboxybetaine surfactants (N-dodecyl-N,N-dimethylammonio)butyrate (DDMAB, CMC =
      4.3 mM) and (N-dodecyl-N,N-dimethylammonio)undecanoate (DDMAU, CMC = 0.13 mM) was
      assessed by protein titration and SDS-PAGE analysis. The maximum yields of
      membrane protein solubilization ranged from 20 to 90%, depending upon both the
      mycoplasma membrane investigated and the surfactant used. In five of six cases,
      the extraction was optimal for surfactant concentrations of ca. 25 mM. DDMAB
      displayed a higher efficiency in membrane protein extraction. The order of
      efficiency for both surfactants was Spiroplasma melliferum > Acholaplasma
      laidlawii > Mycoplasma gallisepticum. In contrast, DDMAU proved much more
      selective. The order of selectivity was M. gallisepticum > S. melliferum > A.
      laidlawii. The highest selectivity was recorded for the major proteins p67 and
      spiralin of M. gallisepticum and S. melliferum, respectively. For p67, notably,
      DDMAU proved superior to 10 other surfactants. Dot immunobinding and crossed
      immunoelectrophoresis analyses showed that both dodecyl carboxybetaines were
      suitable as membrane protein-solubilizing agents in immunological techniques.
      Furthermore, these surfactants did not exhibit effects adverse to the activity of
      A. laidlawii membrane NADH oxidase. One promising application of DDMAU is the
      separation of membrane proteins by ion-exchange HPLC as illustrated by the good
      resolution of M. gallisepticum membrane proteins and purification of p67 to
      almost homogeneity. These data show that dodecyl carboxybetaine surfactants are
      useful for the extraction of mycoplasma membrane antigens under mild
      conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733454
TI  - Measurement of thermally produced volatile alkanes: an assay for plant
      hydroperoxy fatty acid evaluation.
AB  - A new method designed to monitor lipid peroxidation in plants has been set up
      with soybean hypocotyl/radicles. The hydroperoxy fatty acids present in situ are
      converted by rapid thermal treatment (80 s and 210 J g-1) of the biological
      sample into ethane and n-pentane, which are analyzed by gas chromatography. The
      method has been directly calibrated by quantification of the hydroperoxy fatty
      acids by silica-phase HPLC analysis of their reduced hydroxy derivatives.
      Hypocotyl/radicles from the two soybean cultivars Argenta and Soriano were
      submitted to various chemical oxidative treatments and were analyzed for both
      thermally produced volatile alkanes and hydroperoxy fatty acid levels. Our
      results showed that ethane and n-pentane production are in both cases closely
      correlated with linolenic as well as linoleic acid hydroperoxide levels (P <
      0.001). Within a given plant material, thermal conversion of both hydroperoxides
      into alkanes occurred with yields which were not dependent on the oxidative
      treatment. These yields are however functions of the biological material since in
      Soriano and Argenta cultivars they were around 6 and 25%, respectively. Taking
      into account the last point, the alkane test cannot be used to directly quantify
      the absolute lipid hydroperoxide levels of plant tissues but it is convenient to
      monitor the peroxidative phenomenon as it occurs. The assay is easy and rapid to
      perform (analysis of 50 samples per day) since no sample preparation is needed,
      and the low detection limit (20 pmol of alkane g-1) permits the analysis of small
      samples.

PMID- 7733455
TI  - Analysis of monosaccharide composition of mucin oligosaccharide alditols by high
      performance anion-exchange chromatography.
AB  - A simple one-step method for the analysis of monosaccharides including
      galactosaminitol after acidic hydrolysis is described. The hydrolyzate was re-N
      acetylated and analyzed by high-performance anion-exchange chromatography and the
      sugars were detected by a pulsed amperometric detector. The method was applied on
      a mixture of neutral oligosaccharides released from mucin glycopeptides of rat
      small intestine by alkaline borohydride. Sugars were detected down to the
      nanomole range and the results were compared with monosaccharide compositional
      analysis performed by gas chromatography of acetylated alditols.

PMID- 7733456
TI  - Interference of sodium azide with the quantitation of bilirubin: modification of
      Fog's method to eliminate azide interference.
AB  - Interference of sodium azide with bilirubin estimation was studied at different
      concentrations of sodium azide. At an azide concentration (0.08% or 12.3 mM), 99%
      inhibition of the color reaction was observed. Similar results were obtained when
      the effect of sodium azide was studied by fixing bilirubin concentration and
      increasing the azide concentration. The decrease in color reaction can be
      explained on the basis of competition of the two compounds, i.e., bilirubin and
      sodium azide for diazosulfanilic acid. The method was modified to measure the
      concentration of bilirubin in various serum samples containing different amounts
      of sodium azide.

PMID- 7733457
TI  - Analysis of the stoichiometry of Rab protein prenylation.
AB  - Rab5 is a Ras-related GTP-binding protein that is post-translationally prenylated
      with the 20-carbon isoprenoid geranylgeranyl. We have developed a method to
      determine the stoichiometry of prenylation of Rab5, and Rab family members in
      general, based on the cell-free translation of these peptides in the presence or
      the absence of appropriate isoprenoids. Modification of cell-free synthesized
      Rab5 can be monitored by following the conversion of 35S-labeled peptide to a
      greater mobility isoform on urea-gradient sodium dodecyl sulfate-polyacrylamide
      gels. The mobility-shifted isoform also incorporates radiolabel in the presence
      of [3H]mevalonate or [3H]geranylgeranyl pyrophosphate, confirming post
      translational modification with geranylgeranyl. A quantitative assessment of the
      conversion of mobility-shifted Rab5, promoted by prenylation, and the amount of
      incorporated radiolabel from [3H]geranylgeranyl pyrophosphate was achieved by
      excising gel slices containing radiolabeled isoforms and measuring the covalently
      associated radioactivity. Using this approach, we have established that 2 moles
      of geranylgeranyl is attached per mole of Rab5 peptide. A 2:1 molar ratio of
      geranylgeranyl:peptide is observed for both Rab5wt and a truncation mutant,
      Rab5(1-213), containing C-terminal motifs CCXX and XXCC, respectively. When Rab
      proteins ending in CXC are synthesized and processed in vitro, they also
      incorporate geranylgeranyl at a 2:1 stoichiometry, although extended times of
      incubation are required for full modification. Finally, a C-terminal Rab5
      truncation mutant retaining only one cysteine also becomes modified, although
      only a minor fraction is fully processed. This method offers a novel,
      quantitative approach to investigate the stoichiometry of post-translational
      processing of cell-free synthesized peptides without the need to purify the
      native molecules.

PMID- 7733459
TI  - Assembly of high-resolution bacterial artificial chromosome, P1-derived
      artificial chromosome, and cosmid contigs.
AB  - The generation of contiguous physical maps is often complicated by a variety of
      factors including the type of cloning system used. Here we describe procedures
      for the isolation, rapid characterization, and physical mapping of large-insert
      recombinant bacterial clones from total human genomic BAC (bacterial artificial
      chromosome) and PAC (P1-derived artificial chromosome) libraries containing
      clones with an average insert size of 150 kbp. After initial isolation, the
      clones were subjected to a variety of fingerprinting procedures including inter
      Alu PCR, semiautomated fluorescent finger-printing, and EcoRI restriction
      fragment mapping. Individual BAC and PAC clones were also used as probes to
      interrogate arrayed chromosome 19-specific cosmid libraries. The combination of
      analyses facilitated the identification of chromosome-specific large-insert
      clones as well as the construction of a large (1.2 Mb) high-resolution BAC, PAC,
      and cosmid contig in 19q13.2, spanning the region from the carcinoembryonic
      antigen gene family to the X-ray repair cross complementing 1 DNA repair gene.
      This type of approach directly demonstrates the utility of large-insert
      recombinant bacterial clones for the construction of contiguous physical maps of
      entire chromosomes.

PMID- 7733458
TI  - Calibration of size-exclusion chromatography: use of a double Gaussian
      distribution function to describe pore sizes.
AB  - A method for the calibration of size-exclusion chromatographic columns is
      proposed that takes into account the nonlinear dependence of the Stokes radius Rs
      upon the partition coefficient KD. The method is based on the assumption that the
      pore size distribution of a molecular sieve column can be described by the sum of
      two Gaussian distributions and has been successfully tested with low-pressure
      chromatography gels (Sephacryl and Superose) and HPLC gels (TSK SW) over a wide
      range of protein sizes. An application of this method is described, in which
      aggregation states of the membrane protein prostaglandin H2 synthase solubilized
      in nonionic detergents are estimated.

PMID- 7733460
TI  - Modulation of the behavior of a protein in polyacrylamide gel electrophoresis in
      the presence of dodecyl sulfate by varying the cations.
AB  - The denaturation of Aspergillus oryzae alpha-amylase by dodecyl sulfates can be
      modulated by the change of cations among sodium, lithium, and several
      alkanolammonium ions. The denaturation can be detected by polyacrylamide gel
      electrophoresis in the presence of alkanolammonium dodecyl sulfates, particularly
      around 0 degree C where the denaturation reaction can be virtually frozen. The
      moderate stability of the amylase against denaturation by dodecyl sulfates helped
      to demonstrate the difference among the cations. We previously reported a
      significant difference among the dodecyl sulfates in their ability to dissociate
      chlorophyll-protein assemblies. The present results indicated that there is also
      a difference in the ability of the dodecyl sulfates to denature the amylase, a
      monomeric water-soluble protein. Two species, one retaining intact disulfide
      bonds and the other underwent a single sulfhydryl-disulfide exchange reaction,
      were generated during amylase denaturation by dodecyl sulfates.

PMID- 7733461
TI  - Assay of blood and tissue oxaloacetate and alpha-ketoglutarate by isotope
      dilution gas chromatography-mass spectrometry.
AB  - The assay of oxaloacetate and alpha-ketoglutarate in biological samples is
      complicated by their chemical instability and low concentrations. We present a
      quantitative assay for physiological concentrations of these metabolites by
      isotope dilution gas chromatography-mass spectrometry. Samples are spiked with
      the corresponding internal standards of [U-13C4]oxaloacetate and [U-13C5] alpha
      ketoglutarate prior to their treatment with hydroxylamine. After ethyl acetate
      extraction and evaporation of the organic phases, the oximes are converted to t
      butyldimethylsilyl ethers and analyzed by selected ion monitoring gas
      chromatography-mass spectrometry of the [M-57]+ ion in electron impact. Although
      the internal standards of [U-13C4]oxaloacetate and [U-13C5] alpha-ketoglutarate
      are not commercially available, they can easily be synthesized in 30 min by
      reacting [1,2,3,6-13C4]citrate with citrate lyase, and L-[U-13C5]glutamate with
      pyruvate and glutamate-pyruvate transaminase, respectively. Because of their
      chemical instability, the internal standards are prepared on the day of the
      analysis. A stock solution of [1,2,3,6-13C4]citrate is prepared from L-[U
      13C4]aspartate using citrate synthase and glutamate-oxaloacetate transaminase and
      then purified and kept frozen until required. The detection limit of the method
      is 0.05 nmol in a given sample. The method was applied to measurements of
      oxaloacetate and alpha-ketoglutarate in human blood and rat liver.

PMID- 7733462
TI  - Automated carboxy-terminal sequence analysis of polypeptides containing C
      terminal proline.
AB  - Proteins and peptides can be sequenced from the carboxy-terminus with
      isothiocyanate reagents to produce amino acid thiohydantoin derivatives. Previous
      studies in our laboratory have focused on automation of the thiocyanate chemistry
      using diphenyl phosphoroisothiocyanatidate (DPP-ITC) and pyridine to derivatize
      the C-terminal amino acid to a thiohydantoin and sodium trimethylsilanolate for
      specific hydrolysis of the derivatized C-terminal amino acid (Bailey, J. M.,
      Nikfarjam, F., Shenoy, N. S., and Shively, J. E. (1992) Protein Sci. 1, 1622
      1633). A major limitation of this approach was the inability to derivatize C
      terminal proline. We now describe chemistry based on the DPP-ITC/pyridine
      reaction which is capable of derivatizing C-terminal proline to a thiohydantoin.
      The reaction of DPP-ITC/pyridine with C-terminal proline rapidly forms an acyl
      isothiocyanate which is capable of forming a quaternary amine containing
      thiohydantoin. Unlike formation of peptidylthiohydantoins with the other 19
      commonly occurring amino acids in which cyclization to a thiohydantoin is
      concomitant with loss of a proton from the amide nitrogen, proline has no amide
      proton and as a result the newly formed proline thiohydantoin contains an
      unprotonated ring nitrogen. This cyclic structure if left unprotonated will
      regenerate C-terminal proline during the cleavage reaction. However, if
      protonated by the addition of acid, the proline thiohydantoin ring is stabilized
      and can be readily hydrolyzed to proline thiohydantoin and a shortened peptide by
      the addition of water vapor or alternatively by sodium or potassium
      trimethylsilanolate, the reagent normally used for the cleavage reaction. By
      introducing vaporphase trifluoroacetic acid (TFA) for the protonation reaction
      and water vapor for the hydrolysis reaction we have been able to automate the
      chemistry required for derivatization of C-terminal proline.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7733463
TI  - Quantification of hepatitis C virus RNA by competitive reverse transcription and
      polymerase chain reaction using a modified hepatitis C virus RNA transcript.

PMID- 7733464
TI  - Determination of dihydrofolate reductase gene amplification from single cell
      colonies by quantitative polymerase chain reaction.

PMID- 7733465
TI  - An evaluation of primer length on random-primed DNA synthesis for nucleic acid
      hybridization: longer is not better.

PMID- 7733466
TI  - Single-strand conformation polymorphism analysis for the detection of point
      mutations in the mitochondrial DNA.

PMID- 7733467
TI  - Contact transfer method: DNA transfer from polyacrylamide gel.

PMID- 7733468
TI  - Interlaboratory comparison of autoradiographic DNA profiling measurements. 2.
      Measurement uncertainty and its propagation.
AB  - Identifying the intrinsic sources of measurement uncertainty greatly facilitates
      control and further optimization of a measurement system. We have developed a
      model which quantitatively describes the observed interlaboratory variability of
      autoradiographic DNA band sizing. The model focuses on optical imaging
      measurements of band position and the calibration techniques used to convert
      measured band position to reported band size. The imaging component of
      measurement variability is described as a 0.05-0.2% standard deviation in
      determining the relative location of sample and calibration bands on a given film
      image. While developed solely with optical imaging information, the model is
      consistent with interlaboratory band sizing measurement variability observed with
      pristine samples. This interlaboratory variability can be modeled as a 0.2-0.4%
      standard deviation in the relative positions of sample and calibration bands
      across different electrophoretic gels. Further band sizing protocol
      standardization among laboratories would thus be expected to achieve at best a 2
      fold reduction in interlaboratory band sizing variability.

PMID- 7733469
TI  - Design and optimization of a selective subcutaneously implantable glucose
      electrode based on "wired" glucose oxidase.
AB  - An implantable 0.29 mm o.d. flexible wire electrode was designed for subcutaneous
      monitoring of glucose. The electrode was formed by sequentially depositing in a
      0.09 mm deep shielded recess at the tip of a polyimide-insulated 0.25 mm gold
      wire a "wired" glucose oxidase (GOX) sensing layer, a mass transport limiting
      layer, and a nonfouling biocompatible layer. The glucose sensing layer was formed
      by cross-linking (poly[(1-vinylimidazolyl)osmium(4,4'-dimethylbipyridine)2Cl]
      )+/2+(PVI13-dme - Os) and GOX with poly(ethylene glycol) diglycidyl ether (PEG).
      The glucose mass transport restricting layer consisted of a poly(ester sulfonic
      acid) film (Eastman AQ 29D) and a copolymer of polyaziridine and poly(vinyl
      pyridine) partially quaternized with methylene carboxylate. The outer
      biocompatible layer was formed by photo-cross-linking tetraacrylated
      poly(ethylene oxide). The three layers contained no leachable components and had
      a total mass less than 2.2 micrograms (approximately 50 ng of Os). When poised at
      +200 mV vs SCE and operated at 37 degrees C, the 5 x 10(-4) cm2 electrode had in
      vitro a sensitivity of 1-2.5 nA mM-1. The current increased with the glucose
      concentration up to 60 mM, and the 10-90% response time was approximately 1 min
      when the glucose concentration was abruptly raised from 5 to 10 mM. The
      sensitivity decreased by less than 4% over a test period of 1 week, during which
      the electrode was operated continuously in a 10 mM glucose physiological buffer
      solution at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733470
TI  - [Shivering and rigor during the awakening period].
AB  - Muscular hyperactivity presenting as shivering and rigor during the awakening
      period after 116 surgeries with the use of microsurgical technique under balanced
      NLA-based anesthesia was studied. In some cases ketamine (0.5 to 0.75 mg/kg) and
      trilene (0.3 to 0.5 vol.%) were used at the stage of tissue revascularization
      under conditions of controlled and uncontrolled thermal loss. The efficacy of
      special drug (ketamine, trilene) and nondrug (warming measures) components of
      anesthesia preventing shivering and rigor was demonstrated. A correlation between
      the intensity of muscular hyperactivity and the degree of recovery of pain
      sensitivity (r from -0.73 to -0.98) and the level of consciousness recovery (r
      from 0.69 to 0.92) was revealed. The policy of treatment of shivering and chill
      was selected with due consideration for these data. Efficacies of tramal (96%)
      and ketamine (80%) were demonstrated. Nubain was found absolutely unfit for the
      purpose.

PMID- 7733471
TI  - [Hemodynamic disorders in patients with ischemic heart disease after
      aortocoronary bypass during transportation from the operating room to intensive
      care units and their prevention].
AB  - Changes in homeostasis of 33 coronary patients after aortocoronary shunting,
      developing in the course of transportation of the patients to reanimation
      department, were studied. The causes of some shifts in the homeostasis were
      revealed. Methods for the prevention and therapy of these disorders were
      developed.

PMID- 7733472
TI  - [Course of apallic syndrome after clinical death during anesthesia].
AB  - Anesthesiological errors after clinical death during narcosis for strumectomy are
      considered. These errors were continuation of surgery after systole, inadequate
      management of the systemic arterial pressure and cerebral circulation after
      global ischemia, early switch-off of artificial ventilation of the lungs. All
      these steps led to prolonged coma, development of the apallic syndrome, and
      invalidism of the patient.

PMID- 7733473
TI  - [Methodological approaches to studies of the functional state of lungs under
      conditions of intensive care].
AB  - Algorithms for automated processing of curves reflecting respiratory function of
      the lungs (pneumotachygram, psyrogram, transthoracic pressure) in grave patients
      were developed. A system of monitoring the parameters characterizing real time
      pulmonary ventilation, gas exchange, respiratory mechanics and aerodynamics was
      created. The described algorithms for calculating the curves of respiratory
      functions permit examination of pulmonary function during spontaneous respiration
      of a patient.

PMID- 7733474
TI  - [Interleukin-1 in combined detoxification therapy of surgical sepsis].
AB  - Clinical trials of Russian yeast recombinant human interleukin-2 (yrIL-2) were
      carried out in 17 patients with posttraumatic and postoperative sepsis to whom 33
      intravenous drip infusions of the drug were administered as a single infusion or
      courses of 2 to 4 injections in a dose of 1,000,000 U per .1 m2 body surface. A
      positive clinical effect of yrIL-2 in this dose was observed on the next day
      after the first injection of the drug: the signs of intoxication were reliably
      reduced. The immunostimulating effect of yrIL-2 consisted in activation of
      pharmacytizing leukocytes of blood. Addition of yrIL-2 to therapeutic complex for
      patients with sepsis helped reliably reduce the mortality of such patients with
      sepsis helped reliably reduce the mortality of such patients to 29.4% vs. 63.3%
      in controls.

PMID- 7733475
TI  - [Hemodynamic disorders and their correction in peritoneal dialysis of children
      with acute renal failure].
AB  - Hemodynamic disorders occurring during acute renal failure (ARF) in children with
      the hemolytic uremic syndrome and the effects of peritoneal dialysis on
      hemodynamics were studied. A complex of electrophysiological methods was used:
      Integral whole body rheography, electrocardiography, and polycardiography, which
      permitted assessment of the severity and type of hemodynamic disorders in ARF.
      Three main types of hemodynamic changes were observed: hypodynamic, hyperdynamic,
      and normodynamic. The circulation regimen depended on the manifestation of
      extracardiac (hypovolemia, increase of the total peripheral resistance) and/or
      cardiac factors (reduction of the cardiac pump and contractile functions as a
      result of myo- or pericarditis, metabolic disorders in the myocardium).
      Specification of the hemodynamic diagnosis permitted a purposeful correction of
      the hemodynamic disorders (sympathomimetic amines, cardiac glycosides,
      vasodilators, infusion therapy). Peritoneal dialysis had an unfavorable effect on
      the hemodynamics of patients with impaired pump function of the myocardium and of
      those with hypovolemia, deteriorating at the same time the tolerance to volumic
      loading. Dopamine infusion reduced the hemodynamic disorders both "on an empty
      abdomen" and after filling of the abdominal cavity. Goal-oriented correction of
      the hemodynamics helped reduce the circulatory disorders during all stages of
      treatment of ARF.

PMID- 7733476
TI  - [Role of hyperbaric oxygenation in the mechanism of ammonium detoxication in
      resection of the liver in the presence of chronic hepatitis].
AB  - Hyperbaric oxygenation (HBO) used in 170 white rats with chronic CCL4-hepatitis
      after resection of the liver was conducive to repair of the reversible (glutamine
      synthesis) and irreversible (urea synthesis) routes of ammonium binding in
      hepatocytes which are disordered in chronic hepatitis. Hyperbaric oxygen
      regulates the effect of resection of the liver on the glutamine- and urea
      synthesizing function of the hepatocytes in chronic hepatitis. Therapeutic effect
      of HBO persists for 4 days of the posthypoxic period under conditions of
      posthyperoxic hypoxia.

PMID- 7733477
TI  - [Aggregation state of the blood of patients in the early period after surgery
      with artificial blood circulation].

PMID- 7733478
TI  - [Prevention of hemostatic disorders at different stages of surgical treatment in
      patients with colonic cancer].
AB  - The status of the hemostasis system was studied in 40 patients with colonic
      cancer before, during, and after surgery, who were administered no treatment
      before the operation, and in 30 ones administered depogen with heparin in the
      preoperative period. Preoperative treatment with depogen had a favorable effect
      on both coagulation and platelet components of the hemostasis system.
      Administration of depogen together with heparin reduced the intensity of subacute
      chronic intravascular blood coagulation during and after surgery in patients with
      colonic cancer and was conducive to a reduction of the incidence of postoperative
      complications.

PMID- 7733479
TI  - [Diprivan (propofol) in anesthesia for endoscopic surgery of the tracheobronchial
      tree].
AB  - The hemodynamic parameters (BP, HR, YO) were studied in 50 patients aged 9 to 77,
      ASA I-IV, subjected to endoscopic surgery on the tracheobronchial tree. Use of
      ketamine in these patients in schemes of anesthesia before induction with
      diprivan had a favorable effect on the hemodynamic stability and did not
      influence the recovery. Moreover, schemes including ketamine are advisable when
      prolonged artificial circulation is needed by surgical indications (dilatation or
      stenosis).

PMID- 7733480
TI  - [Method of venipuncture].

PMID- 7733481
TI  - [Effective epidural anesthesia on the previously operated spine].

PMID- 7733482
TI  - [Orotracheal intubation in unstable cervical part of the spine: an alternative
      approach].
AB  - A case with a difficult intubation of the trachea in a patient with anterior
      dislocation of C(VI) vertebra and unstable cervical portion of the spine is
      described. A special Bullard fiberoptic laryngoscope was effectively used in this
      patient for orotracheal intubation. Use of this laryngoscope is a good
      alternative to other methods of tracheal intubation in patients with injuries and
      unstable cervical portion of the spine.

PMID- 7733483
TI  - [Dynamics of bioelectric activity of the brain in the acute period of stroke and
      its prognostic significance].
AB  - The electrical activity of the brain was assessed in various periods of acute
      ischemic stroke and its values correlated to the neurological symptoms. Seventy
      six patients with acute ischemic stroke in the median cerebral artery basin were
      examined. A grave course of the disease and slowly progressing positive shifts in
      the neurologic symptoms were associated with the phenomenon of clinico-EEG
      dissociation: an increase in the intensity of abnormally slow activity was wave
      like and recorded both in the involved and intact hemispheres. These pathological
      shifts were maximally manifest at the site of projection of ischemic stroke on
      days 3, 7, and 14 of acute disorder of brain circulation, this permitting the use
      of EEG parameters in these days with prognostic purposes.

PMID- 7733484
TI  - [A new ultrashort-acting general anesthetic, propofol].

PMID- 7733485
TI  - [Lipid peroxidation disorders in surgical patients at various stages of
      treatment].

PMID- 7733486
TI  - [Use of the method of food deprivation in preoperative care of patients with
      concomitant obesity].
AB  - Alimentary deprivation was used in preoperative treatment of 86 surgical patients
      with obesity. Body mass was reduced by 10 to 20%, on an average, and the course
      of concomitant diseases was corrected. Findings of clinical, instrumental, and
      laboratory studies showed that alimentary deprivation was well tolerated by
      surgical patients, improving their resistance to surgical stress.

PMID- 7733487
TI  - [Changes in central hemodynamics and the heart conduction system during total
      intravenous anesthesia using diprivan in extensive abdominal surgery].
AB  - Diprivan was included in the multicomponent intravenous anesthesia during
      extensive prolonged and traumatic operations in abdominal surgery and gynecology.
      The investigations showed the minimal effect of anesthesia with diprivan,
      diazepam, and phentanyl on the central hemodynamics and conducting system of the
      heart. The suggested anesthetic scheme may be a method of choice in patients at a
      high risk of surgical anesthesiological injury.

PMID- 7733488
TI  - [Clinical experience in the use of dormicum (midazolam) in anesthesiology and
      intensive care].
AB  - The authors analyze the efficacy of midazolam (dormicum, Egys, Hungary) used for
      induction anesthesia in 35 patients subjected to planned surgery for varicose
      disease of the lower limbs and on the abdominal organs and in 17 critical
      patients in intensive care units. To assess the hemodynamics, catheterization of
      the peripheral and pulmonary arteries was carried out, cardiac output, pressure
      in cardiac cavities, pulmonary capillary wedging pressure assessed, total
      peripheral and total pulmonary resistance, cardiac and stroke indexes estimated,
      gaseous composition of arterial and mixed venous blood analyzed. The drug had
      virtually no side effects on the function of vital systems of the body. Midazolam
      fully meets the requirements to drugs used for induction anesthesia and is
      compatible to such drugs as barbiturates, diazepam, ketamine. The drug can meet
      pharmacodynamic and pharmacokinetic requirements to sedative agents used in
      intensive care units, excepting analgesia. However, the need in analgesics and
      their doses are reduced during sedative therapy with midazolam. Midazolam effects
      on the lesser circulation hemodynamics permit its use as a sedative agent in
      patients with respiratory distress syndrome and pulmonary artery thromboembolism;
      it is also advisable for induction anesthesia in patients operated on for
      pulmonary artery thromboembolism and in other patients with lesser circulation
      hypertension.

PMID- 7733489
TI  - DNA sequence of the porcine alpha-lactalbumin 5' flanking region and single-base
      polymorphisms within this region.
AB  - The 5' flanking region of the alpha-lactalbumin (alpha-LA) gene was sequenced for
      the Duroc, Yorkshire and Meishan breeds of swine to identify potential sequence
      variants within this regulatory region of the porcine alpha-LA gene. The
      sequenced region of the gene encompasses 391bp5' of the translation start site to
      11bp3' of the translation start site. Within this sequence of the porcine alpha
      LA gene two single-base pair differences were detected. One variant occurs at
      position -178 and the other at position -235 from the translation start site.
      Each of the variations can be detected by a restriction fragment length
      polymorphism within a polymerase chain reaction amplified product. The
      polymorphisms at the -178 and -235 positions appear to be genetically linked in
      the animals that have been analysed.

PMID- 7733490
TI  - Genetic polymorphism of the sixth component of complement (C6) in dogs.
AB  - Using agarose gel isoelectric focusing and immunoblotting with rabbit anti-rabbit
      C6, a genetic polymorphism was found in the sixth component of complement (C6) in
      18 Asian native breeds or populations and three European breeds of dog. The C6
      locus was highly polymorphic. The phenotype distribution data indicated that dog
      C6 phenotypes were controlled by seven codominant alleles,
      C6A,C6B,C6C,C6D,C6E,C6F and C6G, at a single autosomal locus. Breed differences
      were observed among the gene frequencies, especially between Asian and European
      breeds. Two gene flows from the adjacent areas into Japanese native dogs were
      postulated.

PMID- 7733491
TI  - Discrimination between major histocompatibility complex class II DQ and DR locus
      products in cattle.
AB  - We have used a panel of anti-major histocompatibility complex (MHC) class II
      monoclonal antibodies (mAbs) and have assessed their specificity for the products
      of the individual bovine MHC (BoLA) class II subregions. The mAbs identified two
      distinct class II molecules by affinity purification and ELISA. Two-dimensional
      immunoblotting confirmed these data and NH2-terminal sequencing of the purified
      class II alpha chains of one member of each group identified the subregion
      specificity of the mAbs. The mAbs VPM36, TH22A and TH81A are specific for BoLA
      DQ, whereas VPM54, TH14B and J11 are specific for BoLA DR. SW73.2 reacts with
      both MHC subgroups of all cattle tested.

PMID- 7733492
TI  - Development and mapping of ten porcine microsatellite markers.
AB  - Thirty (TG)n microsatellite clones were isolated from a pig genomic library,
      sequenced, and tested for their suitability to detect polymorphism on a panel of
      animals by means of the polymerase chain reaction. Ten of these clones were
      developed into suitable markers and subsequently segregation of these markers was
      determined in the five PiGMaP reference pedigrees. A linkage analysis was
      performed on these 10 microsatellites together with 365 other loci that have been
      typed on these reference families. Eight of the microsatellites have been mapped
      to eight different linkage groups that have been previously assigned to different
      chromosomes (chromosomes 1, 6, 7, 9, 14, 15, 17 and 18). Of the remaining two
      markers, one is X-linked and the other shows no linkage. The number of alleles
      detected by these microsatellites, in the reference pedigrees, varied from six to
      sixteen and the heterozygosity varied from 42 to 85% in the 26 unrelated founder
      animals of these reference pedigrees.

PMID- 7733493
TI  - Alignment of two genetic linkage maps on porcine chromosome 13.
AB  - A set of four microsatellite markers from the USDA genetic linkage map of porcine
      chromosome 13 were mapped in the European Pig Gene Mapping Project (PiGMaP)
      reference pedigrees. A two-point linkage analysis was performed between these
      markers and a set of markers known to map to chromosome 13. Pairs of markers that
      had a lod score greater than three were used to construct a multi-point linkage
      map, permitting alignment of the United States Department of Agriculture (USDA)
      map to the PiGMaP.

PMID- 7733494
TI  - Dinucleotide repeat polymorphism at the bovine HAUT1 and HAUT14 loci.

PMID- 7733495
TI  - Equine parentage testing by microsatellite locus at chromosome 1q2.1.

PMID- 7733496
TI  - Three bovine chromosome 15 microsatellite markers.

PMID- 7733497
TI  - Five polymorphic ovine microsatellites.

PMID- 7733498
TI  - A TaqI RFLP at the bovine INHA locus.

PMID- 7733499
TI  - Three porcine polymorphic microsatellite loci (S0075, S0151, S0158).

PMID- 7733500
TI  - Five bovine microsatellite markers derived from skeletal muscle cDNA: RME01,
      RME11, RME23, RME25 and RME33.

PMID- 7733501
TI  - Nucleotide substitution in the bovine FSHB 5'-region.

PMID- 7733502
TI  - Bovine microsatellite mononucleotide and dinucleotide repeat polymorphisms at the
      TEXAN6, TEXAN7, TEXAN8, TEXAN9 and TEXAN10 loci.

PMID- 7733503
TI  - Ovine microsatellites at the OarCP9, OarCP16, OarCP20, OarCP21, OarCP23 and
      OarCP26 loci.

PMID- 7733504
TI  - Ovine microsatellites at the OarCP34, OarCP38, OarCP43, OarCP49, OarCP73, OarCP79
      and OarCP99 loci.

PMID- 7733505
TI  - RFLP markers for the porcine INHA locus.

PMID- 7733506
TI  - Two polymorphic bovine microsatellite loci (AFR227 and AFR2215).

PMID- 7733507
TI  - Eighteen canine microsatellites.

PMID- 7733508
TI  - RFLPs at the porcine locus encoding the type I-alpha regulatory subunit of the
      cAMP-dependent protein kinase (PRKAR1A).

PMID- 7733509
TI  - Genotyping bovine milk proteins using allele discrimination by primer length and
      automated DNA sizing technology.
AB  - A method for genotyping kappa-casein (A, B, E), beta-casein (A1, A2, A3, A5, B)
      and beta-lactoglobulin (A, B) simultaneously by the use of allele discrimination
      by primer length combined with automated detection of fragments with a sequencing
      instrument is described. Seven different mutations within the milk protein genes
      were analysed in order to distinguish between the alleles examined. The samples
      were amplified in two separate multiplex polymerase chain reactions (PCRs), which
      were then pooled and separated according to size in a single lane on the gel. By
      using stringent PCR conditions, we have been able to achieve allele-specific
      amplifications and minimize amplification of mis-matched primer for all seven
      mutations.

PMID- 7733510
TI  - Functional genes mapped on the chicken genome.
AB  - Microsatellite polymorphisms are finding increasing use in genetics. In addition
      to the random isolation of microsatellite markers, such markers can also be
      developed from sequences already present in public domain databases. An advantage
      of public domain databases is that these microsatellites are known to be located
      within or close to identified functional genes. In this study the GenBank and
      EMBL databases were screened for microsatellite markers and primers were defined
      for amplification. Subsequently, these markers were tested on a panel of five
      different birds from layer and broiler stocks and on the international reference
      families: the East Lansing reference family and the Compton reference family. Of
      the 33 loci tested, 25 were polymorphic on the test panel and from these 25, 14
      were polymorphic in one or both reference families. Twelve of the 14 loci that
      could be mapped fell into previously defined linkage groups. The other two
      markers were not linked. Because three of the loci had previously been mapped to
      specific chromosomes by in situ hybridization, linkage groups E6 and C3 could be
      assigned to chromosome 6, E5 and C17 to chromosome 4 and E21 to one of the
      microchromosomes.

PMID- 7733511
TI  - Analysis of the fine specificities of sheep major histocompatibility complex
      class II-specific monoclonal antibodies using mouse L-cell transfectants.
AB  - The fine specificities of two panels of monoclonal antibodies (mAbs) for sheep
      major histocompatibility complex (MHC) class II molecules were determined using
      five mouse L-cell transfectants, each expressing a defined sheep DQ or DR MHC
      class II A/B gene pair. Using the transfectants in an indirect fluorescence
      antibody assay, previous immunochemical characterization of the mAbs was
      confirmed for 16 of 23 mAbs tested. The MHC class II subtype specificity (DQ or
      DR) of each mAb was assigned without interference from the products of other
      expressed class II loci. This allowed the identification of both cross-locus
      specificities as well as defining fine specificities of mAbs previously only
      partially characterized by immunochemical techniques.

PMID- 7733512
TI  - Six loci mapped on to human chromosome 2p are assigned to sheep chromosome 3p.
AB  - Six loci, apoliproprotein B (including Ag(x) antigen), immunoglobulin kappa
      constant region (IGKC), luteinizing hormone/choriogonadotrophin receptor, avian
      myelocytomatosis viral related oncogene, neuroblastoma derived, ornithine
      decarboxylase, and proopiomelanocortin (adrenocorticotropin/beta-lipotropin)
      (POMC), were newly assigned to sheep chromosome 3p using a chromosomally
      characterized minipanel of sheep-hamster cell hybrids. Isotopic in situ
      hybridization of IGKC to sheep chromosome 3p22-p17 is reported, confirming the
      cell hybrid assignment. As these loci are all known to map to human chromosome
      2p, this study demonstrates that this chromosomal segment is extensively
      conserved in sheep. Only POMC has been previously assigned to cattle chromosome
      11, which is the equivalent of sheep chromosome 3p. Therefore, we predict that
      the other loci assigned in this study to sheep 3p are likely to be located on
      cattle 11. The provisional assignment of an additional locus, annexin-like to
      sheep chromosome 3p is also reported.

PMID- 7733513
TI  - [Value of D(-) lactate determination for the fast diagnosis of meningitis after
      craniotomy. An initial study].
AB  - The early diagnosis of postoperative bacterial meningitis (BM) may be difficult.
      CSF cultures may remain sterile. Clinical features and routine laboratory data
      often fail to give an evidence. As early antibiotic therapy is essential in such
      patients, a rapid diagnosis is required. Different authors proposed the D(-)
      isomer of lactic acid as an early and effective marker of infection in the body
      fluids (including CSF). D(-) lactate is produced by bacteriae and fungi; L(+)
      lactate may be produced also by human tissues in anaerobic situations. We
      conducted a prospective study in a neurosurgical intensive care unit to evaluate
      this technique for the diagnosis of meningitis following craniotomy. Fifty-four
      patients were included, 40 in group A (not infected or infected out of the CNS),
      4 in group B (suspected BM), 10 in group C (BM with positive CSF cultures). No
      patient suffered from septicemia, haemodynamic or ventilatory instability, nor
      metabolic disorder. Clinical data, CSF and blood samples (cytology, conventional
      biochemistry, D(-) and L(+) lactate, bacteriology) were collected at inclusion
      and, in group B and C patients, at day 2, 5 and at clinical recovery. D(-)
      lactate measurements were performed with an enzymatic method adaptated from a
      Boehringer Mannheim kit (for determination in foodstuff). Statistics were based
      on the comparison of group A vs C patients. D(-) and L(+) lactate concentrations
      in the CSF were significantly higher in group C patients, and blood
      concentrations were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733514
TI  - [Nutrition proteins and muscular catabolism in severely burnt patients.
      Comparative effects of small peptides or free amino acids].
AB  - The beneficial effects of high caloric and protein enteral diet on wound healing
      and prevention of infection in severely burned patients is well documented.
      However, the relative proportion of each nutrient and especially the form of
      nitrogen supply have not yet been clearly established. The aim of this study was
      to compare, in severely burned patients, the efficiency of a partial protein
      hydrolysate and free amino acid formula during a 15-day enteral feeding. Twenty
      burned patients ranging in age from 18 to 67 years with a mean burn size of 40 +/
      12% of total body surface area, of which 31 +/- 14% was deep dermal, were
      studied prospectively and randomised in two groups. Group A received the free
      amino acid diet which was obtained by hydrolysis of the protein hydrolysate given
      to Group B (60% small peptides). All diets contained a nitrogen source of similar
      amino acid composition. Nitrogen balance was measured daily and serum protein
      concentrations were determined on days 0, 4, 8, 11 and 15. Anthropometric
      parameters, urinary 3 methylhistidine/creatinine ratio and plasma amino acid
      concentration were assessed on days 0, 8 and 15. Daily and cumulative nitrogen
      balance at D15 did not differ between the two groups. In group A, the circulating
      visceral proteins increased at all times of the study without decrease of acute
      phase reactant, whereas only transthyretin and retinol binding protein increased
      at D11 and D15 with a significant decrease of C-reactive protein at the same time
      in the other group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733515
TI  - [Lack of sensitivity to per-anesthetic malignant hyperthermia in 32 patients who
      developed neuroleptic malignant syndrome].
AB  - The aim of this study was to verify whether a relationship exists between
      neuroleptic malignant syndrome (NMS) and anaesthetic-induced malignant
      hyperthermia (MH) or not. The in vitro halothane-caffeine tests were performed on
      muscle tissue obtained from 32 patients with documented NMS episodes. The
      diagnosis of NMS relied on Levenson's criteria. The results, expressed in
      accordance with the criteria of the European MH Group, defined 29 subjects as MH
      non-susceptible. Three patients were classified as MH equivocal. These findings
      demonstrate the lack of any link between NMS and MH. Therefore, patients with a
      history of NMS are not likely to be at risk of developing MH and special measures
      against MH are not required for anaesthesia in these patients.

PMID- 7733516
TI  - [Survey of the quality of sleep during the perioperative period. Study of factors
      predisposing to insomnia].
AB  - In order to assess the quality of sleep in surgical patients the amount of self
      rated postoperative insomnia and its predisposing factors, we conducted a three
      fold questionnaire * survey in 176 consecutive patients undergoing elective
      orthopaedic, vascular or abdominal surgery. The first questionnaire was completed
      the day preceding surgery, the second at the day of discharge and the third two
      weeks later. This survey concerned the patient's general status, his usual sleep
      profile and factors which could interfere with sleep (hypnotics, pain,
      environmental factors) throughout the study period. It allowed quantification of
      these parameters and the assessment of their time-course. Perioperative insomnia
      appeared to be a long-lasting phenomenon which persisted after discharge. Factor
      analysis and multiple regression models showed that postoperative, self-rated
      insomnia was multifactorial and mainly explained by the amount of postoperative
      pain (p = 0.035).

PMID- 7733517
TI  - [Intestinal mucosa injury during experimental endotoxin-induced shock].
AB  - To ascertain tissue oxygenation during conversion from hypo to hyperdynamic state
      with vascular volume expansion, venous outflow from a segment of ileum was
      isolated in anesthetized and pump-ventilated endotoxic dogs to measure gut oxygen
      uptake (VO2), lactate metabolism, intramucosal PCO2 and tissue PO2 (PtiO2).
      Tissue PO2 was measured by multipoint surface Mehrdraht Dortmund Oberflache
      electrodes placed on mucosal and serosal surfaces of gut. Six dogs were infused
      with 2 mg.kg-1 E. coli lipopolysaccharide (LPS) in one hour followed by a two
      hour 0.5 mL.kg-1.min-1 dextran infusion. Two dogs were used as controls and
      received dextran infusion in order to assess time and hemodilution-dependent
      effects. LPS infusion resulted in an hypodynamic sepsis with supply limited VO2,
      increased arterial lactate and increased lactate output by gut. Resuscitation
      resulted in an hyperdynamic sepsis with improvement of whole-body VO2. In the
      gut, VO2 remained low and intramucosal PCO2 as well as lactate output remained
      high, despite increased flow. Gut PtiO2 results suggested blood flow
      maldistribution with tissue hypoxia in the mucosa despite increased total flow to
      the gut. Gut VO2, lactate flux, intramucosal PCO2, and tissue PO2 were consistent
      with regulatory responses that shut down mucosal perfusion and oxygenation in
      spite of increased blood flow to gut.

PMID- 7733518
TI  - [Comparison of cardiac output measured continuously by thermodilution and
      calculated according to Fick's principle].
AB  - Recently, a thermodilution technique for continuous measurement of cardiac output
      was introduced. The aim of this study was to evaluate the accuracy of continuous
      cardiac output measurement using the thermodilution technique (CCO) and to assess
      the correspondence between CCO and cardiac output obtained with the Fick's
      principle (Fick-CO). Nine patients were studied in the postoperative period after
      cardiac surgery. A new pulmonary artery catheter modified by attachment of a
      thermal filament (Intellicath, Model PA3-H-8Fr) was inserted and connected to a
      continuous cardiac output computer (Vigilance Monitor). Oxygen consumption was
      continuously measured using the gas exchange method (Deltatrac Metabolic
      Monitor). Fick-CO was calculated according to the Fick's principle. The study in
      each patient consisted of 6 serial determinations of both CCO and Fick-CO at 10
      min intervals. For 54 pairs of measurements, the mean difference (Fick-CO-CCO)
      was 0,6 L.min-1. The limits of agreement were--0,6 to 1,8 L.min-1 respectively.
      The relative error was 6% for CCO and 10% for Fick-CO. It is concluded that CCO
      and Fick-CO cannot be considered as being interchangeable. However, the accuracy
      of CCO is acceptable. The technique does not require any user calibration and
      eliminates the need of bolus injections. Further studies are necessary to
      determine the benefits of this new technique in the various clinical situations.

PMID- 7733519
TI  - [Do halogenated anesthetics protect from ischemic and reperfusion myocardial
      injuries?].
AB  - Ischaemia and reperfusion of the myocardium are associated with cellular injuries
      leading to a decrease of contractile function and the occurrence of arrhythmias.
      As reperfusion of an ischaemic heart results in an intracellular overload of
      calcium, a calcium blocking agent pretreatment has been shown to exert a
      protective effect. By altering myocardial calcium fluxes, volatile anesthetics
      might also protect the myocardium from ischaemic damage and reperfusion injuries.
      A beneficial effect of volatile anesthetics on the ischaemic myocardium has been
      shown in numerous studies. These agents decrease the severity of ischaemia as
      well as the incidence of reperfusion arrhythmias and improve recovery of
      myocardial mechanics during reperfusion. They also preserve myocardial energetics
      and protect from oxygen-derived free radicals injury. However, some studies do
      not support these protective effects. The wide discrepancy between the various
      protocols might explain the discrepancy of the results. Enflurane and halothane
      seem to be more efficient than isoflurane. This cannot only be explained by
      different cardiovascular effects, but also by a specific effect on myocardial
      cells. Halothane and enflurane mainly decrease intracellular calcium availability
      by a direct effect on sarcoplasmic reticulum, while isoflurane only decreases the
      transsarcolemnal calcium entry. Enflurane and halothane have more beneficial
      effects than isoflurane on free radicals induced myocardial injuries. In
      conclusion, despite a wide diversity between the different studies, halothane and
      enflurane have better protective properties against ischaemia and reperfusion
      myocardial injuries than isoflurane.

PMID- 7733520
TI  - [Nosocomial pneumonia in intensive care. Value of different diagnostic tools].
AB  - The authors analyzed in published studies providing histologic data the value of
      diagnostic means of nosocomial bronchopneumonia (NBP) in critically ill patients.
      At least 10% of patients whose trachea is intubated and the lungs mechanically
      ventilated suffer an histologically-confirmed NBP. Histology of NBP consists of
      non systematized foci of infection, localised in 90% of cases in the posterior
      segments of the lower pulmonary lobes. In fact, small foci are disseminated in
      both lungs, usually within large areas of non infectious pulmonary lesions and
      are often multimicrobial. This may explain why the clinical and radiological
      diagnosis is inaccurate in more than 40% of cases. On chest X-ray, aeric
      bronchogram and alveolar infiltrates are suggestive but non-specific for NBP, as
      are also fever, leukocytosis and purulent sputum. Therefore, to confirm the
      diagnosis of infection and to isolate the microorganisms responsible for NBP,
      additional investigations are required whose interpretation is uneasy. In a
      simplified manner, bacteriological inoculum takes a course parallel to the
      histological bronchopulmonary lesions: no bacteria in the absence of infection,
      high bacterial inoculum in case of confluent NBP, intermediary in case of
      bronchitis, however with exceptions when antibiotherapy has recently been
      modified. In fact, neither bronchial protected brushing nor broncho-alveolar
      lavage techniques have a perfect sensitivity and specificity. As an example, a
      diagnostic procedure in assessed in calculating the probability of an accurate
      diagnosis of NBP. It is concluded that diagnosis of ventilator-associated
      pneumonia remains still unreliable with the means available today.

PMID- 7733521
TI  - [Curare and burns].
AB  - Burns of more than 15% of the body surface area result in major physiological
      changes with an alteration of cardiovascular, pulmonary, hepatic and renal
      functions, as well as modifications in the pharmacokinetics and the
      pharmacodynamics of many drugs. Among these, a major change in the activity of
      muscle relaxants occurs which can be specific to this pathology. Succinylcholine
      is contra-indicated during recovery from a burn trauma because of a possible
      hyperkaliemic response, directly related to the dose, the post-burn delay and the
      area of burned body surface. The kaliemic response and the related cardiac
      complications remain unpredictable. The height of twich depression with small
      doses of succinylcholine such as 0.1 to 0.2 mg.kg-1, demonstrates the
      hypersensitivity to this agent and does cause neither metabolic disturbances nor
      cardiac arrest. Nevertheless, the administration of succinylcholine is contra
      indicated for from the 5th day on at least two years after the burn injury.
      Conversely, the action of non-depolarizing muscle relaxants is characterized by a
      resistance, which is correlated to both the post-traumatic delay and the extent
      of the burned area. It starts on about the seventh day, reaches peak intensity
      between day 15 and day 40 and can persist up two years after the thermal injury.
      In the course of a burn, the so-called "immature" acetylcholine receptors,
      characterized by the substitution of the sub-unit epsilon by a protein gamma,
      increase at the level of the end plate areas and the extra-synaptic muscle
      membrane. These receptors explain both the hyperkaliemic response and the
      hypersensitivity to succinlycholine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733522
TI  - [Pollution and retro-pollution by the distribution system of medical gases].
AB  - The anaesthetic machine, the recovery room or the ICU ventilator as well as any
      other simple oxygenation device can be accidentally supplied with a "wrong" gas,
      or a mixture of "wrong" and "true" gases, or a gas containing chemical
      impurities, as a result of one of the following causes: a) the source of the
      medical gas pipeline supply contains a "wrong" gas or impurities; b) the gas
      pipeline is polluted by a "wrong" gas or solvents, introduced during the
      installation or maintenance of the pipeline; c) the pipeline is polluted by a
      wrong gas at a point of inter-connection or cross-connection of two pipelines; d)
      supply of a "wrong" gas through wrong quick couplers connected to the pipeline;
      e) back flow of a gas in another pipeline supply through a defective gas mixer,
      which is today the most common cause of pipeline contamination or retropollution.
      It occurs with some types of mixers in case of absence or malfunction of non
      return valves, associated with a pressure difference between the two gas lines.
      The means of prevention, recognition and emergency treatment of these events
      include: a) systematic removal of mixers and flowmeter-mixers from supplies when
      not in use; b) periodical checking of these devices for an accidental
      communication between the gases to be mixed; c) systematic use of an oxygen
      analyser for a continuous measurement of FIO2, especially when the machine is
      connected to the N2O pipeline supply; d) the presence of a reserve cylinder of
      oxygen connected to every anaesthetic machine.

PMID- 7733523
TI  - [Thromboembolic accidents in in vitro fertilization].
AB  - The authors describe four thromboembolic accidents in vitro fertilisations. These
      accidents were not associated with an ovarian hyperstimulation syndrome. However,
      all patients presented a risk factor of thrombosis. The relationship between
      endocrine treatment and the occurrence of side effects is discussed.

PMID- 7733524
TI  - [Tetraplegia in fat embolism].
AB  - This is a report of two cases of tetraplegia complicating fat embolism after
      fracture of long bones. In the first case, a 26 year-old male sustained fractures
      of femur and tibia. One day after admission, the patient became comatose (Glasgow
      coma score = 6) with dyspnaea and petechiae present on the anterior chest wall.
      In second case, a 22 year-old man with a fracture of tibia and humerus, suffered
      two days after admission from similar signs of fat embolism (dyspnaea, Glasgow
      score coma = 6, petechiae). A tetraplegia occurred after 7 days in the first
      patient and 6 days in the second. No lesions were visible on brain CT scan.
      Magnetic resonance imaging showed relative high-intensity areas on T2 weighted
      views. The outcome at three weeks was favourable, without neurologic sequelae.

PMID- 7733525
TI  - [Early diagnosis of traumatic extra-pericardial luxation of the heart. Value of
      tomodensitometry. Apropos of a case].
AB  - Heart luxation is a rare complication of chest trauma. The rupture of pericardium
      must be diagnosed as soon as possible, particularly before prolonged orthopaedic
      surgery for multitrauma, as a cardiac arrest may occur during anaesthesia. This
      report underlines the difficulties of diagnosis in a 40-year-old patient with
      head trauma, chest trauma and multiple fractures. The diagnosis was suspected on
      unstable blood pressure and left lung atelectasis. The computed tomography showed
      herniation of the left ventricle. Emergency thoracotomy showed the left rupture
      of pericardium with complete left heart dislocation. Orthopaedic operation was
      carried out three days later. Computed tomography in multitrauma patients, seems
      to be decisive for early diagnosis of heart luxation. Emergency thoracotomy is
      essential.

PMID- 7733526
TI  - [Value of octreotide in the treatment of postoperative enterocutaneous fistula].
AB  - Two patients with enterocutaneous fistulas (ileal and duodenal) were successfully
      treated with bowel rest, total parenteral nutrition and the somatostatin analogue
      octreotide (150 micrograms.day-1 and 300 micrograms.day-1 respectively). At the
      time octreotide was started the first patient had a high output fistula (1 000
      mL.day-1), the second had a low output fistula (120 mL.day-1). Within 24 hours of
      treatment, a reduction of at least 40% of the output was observed. The time
      intervals to fistula closure were respectively 6 days and 10 days after
      initiation of octreotide therapy. Glucose intolerance was not observed. The
      efficacy of octreotide combined with total parenteral nutrition supports its
      routine use instead of somatostatin, more expensive, less tolerated and
      presenting the risk of rebound effect.

PMID- 7733527
TI  - [Distribution of a hypoxic gas mixture by retro-pollution of a medical gas
      distribution system].
AB  - The authors report a case of retropollution through the defective gas mixer of a
      Logic O4T-IMV ventilator (Ohmeda) located in the recovery room. Due to a
      defective check valve inside the mixer, medical air entered into the oxygen
      pipeline when the O2 pressure decreased below the pressure inside the medical air
      pipeline. This incident resulted in episodes of hypoxic gas mixture delivery in
      the operating theatre, when nitrous oxide was associated with oxygen polluted
      with medical air. The occurrence of such an incident, rarely described so far,
      requires the association of several factors. It can be recognized without delay
      with the continuous use of an oxygen analyser.

PMID- 7733528
TI  - [Chloral hydrate poisoning].
AB  - The intentional ingestion of 5 g of chloral hydrate by a 67-yr-old man resulted
      in cardiac arrhythmia including tachyarrhythmia and polymorphic ventricular
      extrasystoles. As the ingested agent was unknown at admission, the patient was
      treated among others with sodium lactate, a non validated therapy of arrhythmia
      caused by chloral hydrate overdose. The discontinuation of arrhythmia was in
      favour of a beneficial effect of this treatment which remains to be confirmed.
      This unusual therapy is the original point of this case report which allows to
      question the so-called innocuousness of chloral hydrate, to remind the
      conventional treatment of the arrhythmias caused by this agent, the place of beta
      adrenergic blockers, as well as the therapeutic difficulties when the causative
      agent remains unknown.

PMID- 7733529
TI  - [Risks of hydrogen peroxide irrigation in military surgery].
AB  - Two cases of severe complications due to injection of hydrogen peroxide under
      pressure into areas of muscular attrition in war wounds are reported. In both
      cases the administration of hydrogen peroxide was associated with tachypnoea,
      with major arterial desaturation and a precordial "mill-wheel" murmur was heard.
      In one case, these symptoms were followed by hemiplegia caused by paradoxical
      arterial gas embolism, and in the other case by a pulmonary oedema confirmed by
      computerized tomography. Both patients recovered under hyperbaric oxygen therapy.
      The release of gaseous oxygen under the effect of tissue catalase and the
      membrane peroxydasic activity of hydrogen peroxide initiate such complications.
      The injection of hydrogen peroxide under pressure into a closed or partially
      closed cavity should therefore be strictly prohibited.

PMID- 7733530
TI  - [The Univent tube: a substitute to double lumen tubes].
AB  - The Univent tube was designed as an alternative to double lumen endotracheal
      tubes. It is a conventional single lumen tube with an additional small channel
      within the concave anterior wall portion that houses a movable bronchial blocker
      used for lung isolation. A thin lumen in the blocker itself allows lung deflation
      and various ventilatory patterns (oxygen inflow, CPAP, jet-ventilation) in the
      blocked lung. Main indications for the Univent tube include difficult intubation,
      risk of aspiration and planned postoperative ventilation. The "blind" insertion
      of the bronchial balloon carries a high risk of primary malpositioning or
      secondary displacement that may cause a loss of the lung isolation or even
      tracheal obstruction. Initial insertion with fiberoptic bronchoscope is therefore
      required and this device must also be available during the whole period of one
      lung ventilation. High pressures generated by the bronchial cuff and higher cost
      than that of double lumen endotracheal tubes are two other factors that limit the
      use of the Univent tube.

PMID- 7733531
TI  - [Simplified locoregional anesthetic technique for the surgery of the thumb].
AB  - Finger surgery is a frequent procedure, of short duration unless in case of major
      trauma, and often performed in emergency circumstances. In order to improve this
      type of treatment, we have developed distal blockade techniques. The double
      innervation in the thumb requires two punctures; a) dorsal, in order to block the
      superficial branch of the radial nerve; b) palmar, through the flexor tendon
      sheath, allowing the blockade of the digital nerves, outing from the median
      nerve. We use bupivacaine 0.5% without adrenaline, which offers high quality
      anaesthesia and analgesia. This technique can be used outside the operating room,
      in emergency or X-ray rooms. It allows thumb anaesthesia, either alone for short
      duration or in an addition to a plexus blockade whose effect in the radial nerve
      area would be insufficient.

PMID- 7733532
TI  - [Treatment of status epilepticus by continuous infusion of lidocaine].

PMID- 7733534
TI  - [Traumatic asphyxia: a precise clinical entity].

PMID- 7733533
TI  - [Streptococcus pneumoniae pneumonia with late onset in intensive care].

PMID- 7733535
TI  - [Sedation or ventilation?].

PMID- 7733536
TI  - [Addition of a reserve oxygen bottle to the anesthetic respiration device].

PMID- 7733537
TI  - [Prevention of pain during venous puncture in children].

PMID- 7733538
TI  - Bootstraps taxometrics. Solving the classification problem in psychopathology.
AB  - Classification in psychopathology is a problem in applied mathematics; it answers
      the empirical question "Is the latent structure of these phenotypic indicator
      correlations taxonic (categories) or nontaxonic (dimensions, factors)?" It is not
      a matter of convention or preference. Two taxometric procedures, MAMBAC and
      MAXCOV-HITMAX, provide independent tests of the taxonic conjecture and
      satisfactorily accurate estimates of the taxon base rate, the latent means, and
      the valid and false-positive rates achievable by various cuts. The method
      requires no gold standard criterion, applying crude fallible diagnostic
      "criteria" only in the phase of discovery to identify plausible candidate
      indicators. Confidence in the inference to taxonic structure and numerical
      accuracy of latent values is provided by multiple consistency tests, hence the
      term coherent cut kinetics for the general approach. Further revision of
      diagnostic systems should be based on taxometric analysis rather than on
      committee decisions based on clinical impressions and nontaxometric research.

PMID- 7733539
TI  - Clinical practice, university research, and students. A historical perspective on
      anxiety management training.
AB  - This article is based on an address that was given at the 1994 annual convention
      of the American Psychological Association in Los Angeles. This article briefly
      covers the role undergraduate and graduate students had in research on anxiety
      throughout the author's professional career. Emphasis is placed on findings
      regarding anxiety management training (AMT), a short-term therapy for anxiety and
      anger. Such findings cover the initial validation study as well as examples of
      the diverse clinical applications of AMT. In general, this article demonstrates
      an integration of educational training, university-based research, and clinical
      applications.

PMID- 7733540
TI  - Persistent sciatic artery in association with varicosities and limb length
      discrepancy: an unrecognized entity?
AB  - The persistence of the sciatic artery is an unusual occurrence, with an
      angiographically demonstrated incidence of 0.06%. There have been 71 cases
      previously reported. We report an additional case in a 14-year-old boy who
      presented with a chief complaint of unsightly varices. The involved right limb
      was notably shorter than the uninvolved left lower extremity. Work-up included
      physical examination, duplex studies, venography, and angiography. Our patient
      was found to have a patent deep venous anatomy with valvular incompetency
      associated with complete persistence of the sciatic artery and a foreshortened
      right leg. He has done well with conservative treatment. The persistence of a
      sciatic artery has occasionally been associated with other anomalies including
      Mullerian and left renal agenesis, A-V fistula formation, hypertrophy or
      hypotrophy, multiple hemangiomata, neurofibromatosis, or anomalies of leg
      arteries. The literature describes three previous case reports in which patients
      presented with gross varicosities and were incidentally found to have persistent
      sciatic arteries as well as limb length discrepancies. Our patient is a fourth
      example of this syndrome. This pattern of physical attributes has not been
      previously described as a distinct entity. The association of venous
      incompetency, limb discrepancies, and persistence of the sciatic artery may be an
      incidental finding or may represent a related embryologic event. This
      relationship merits consideration in a young patient presenting with severe
      venous varicosities.

PMID- 7733541
TI  - The role of preoperative localization in primary hyperparathyroidism.
AB  - Hyperparathyroidism is being increasingly recognized by the detection of
      hypercalcemia on routine blood chemistry. Improvement in preoperative
      localization has been proposed as a way to decrease operative time and decrease
      morbidity and mortality. The purpose of this study was to retrospectively review
      the Guthrie Clinic experience of parathyroidectomy with and without preoperative
      localization. One hundred nineteen patients who presented with primary
      hyperparathyroidism between 1983 and 1990 were evaluated. There were 27 males and
      91 females with an average age of 61. Preoperative localization resulted in a
      significant decrease in operative time with preoperative localization decreasing
      operative time from 97 minutes without localization to 70 minutes with
      localization. Also, complications were less in patients undergoing preoperative
      localization (5.8% versus 13.9%). Preoperative localization was positively
      affected by gland size, with larger glands being easier to localized. In
      conclusion, accurate preoperative localization decreases operative time and
      decreases complications in this series of patients undergoing exploration for
      primary hyperparathyroidism. In our institution the thallium technitium scan is
      most accurate and is the localization procedure of choice.

PMID- 7733542
TI  - Jejunoileal bypass-induced liver dysfunction and bacterial translocation: effect
      of intraluminal glutamine-infusion.
AB  - We tested the effect of long-term intraluminal administration of glutamine on
      jejunoileal bypass (JIB) induced abnormalities in the plasma-liver profile in
      rats. Male Sprague Dawley rats (200-250 g) were subjected to an end to side JIB
      followed by daily intraluminal infusions of either 8 ml saline (n = 5), infused
      over a 4-hour period, or 8 ml saline containing 1g/Kg body weight glutamine (n =
      7) for 3 weeks. Thirteen unoperated rats and four JIB rats without infusions
      served as controls. At the conclusion of the experiment, a cardiac blood sample
      was removed and analyzed for plasma cholesterol, albumin, total protein, gamma
      glutaril transferase, lactic dehydrogenase, glutamic-oxaloacetic transaminase,
      glutamic pyruvic transaminase, alkaline phosphatase, and bilirubin. Tissue
      samples from various segments of bowel, liver, mesenteric lymph nodes, and spleen
      underwent histopathologic examination. Bacteriological cultures were prepared
      from jejunum, ileum, mesenteric lymph nodes, liver, and spleen. Bacterial
      translocation occurred in both JIB-saline and JIB-glutamine infused rats.
      Glutamine-infused rats developed a significant decrease in the plasma cholesterol
      levels. However, glutamine did not prevent the JIB-induced alterations in the
      plasma-liver profile and bowel histopathology. It is suggested that experimental
      JIB procedure can be used as a model of bacterial translocation consequent to
      mucosal permeability and intestinal inflammatory diseases.

PMID- 7733543
TI  - Interaction of vecuronium with piperacillin or cefoxitin evaluated in a
      prospective, randomized, double-blind clinical trial.
AB  - Interactions between beta-lactam antibiotics, particularly acylaminopenicillins,
      and vecuronium, a widely used muscle relaxant, leading to prolonged neuromuscular
      blockade have been reported in studies of experimental animals and in a few
      clinical case reports. In the clinical reports, however, confounding factors
      always existed. A clinical trial to evaluate interactions between vecuronium and
      cefoxitin or piperacillin was conducted. Patients having major operations
      requiring both muscle relaxants as part of general anesthesia and prophylactic
      antibiotics were entered into the trial and randomly assigned to receive either
      cefoxitin or piperacillin. The electromyographic twitch response was measured
      before and after administration of the antibiotic. Five of 27 evaluable patients
      had minor prolongation of the time to recovery of baseline twitch. No prolonged
      neuromuscular blockade was observed. There were no differences in responses
      between the two antibiotic treatment groups. Cefoxitin and piperacillin
      administered pre- or intra-operatively are not associated with clinically
      important prolongation of muscle relaxation induced by vecuronium. The potential
      for prolongation of neuromuscular blockade induced by vecuronium through
      concomitant administration of piperacillin or cefoxitin as antibiotic prophylaxis
      was investigated in a clinical trial of 30 patients having major abdominal
      operations. Quantitative measurement of neuromuscular blockade was done using the
      electromyographic twitch response to a supramaximal current stimulus.

PMID- 7733544
TI  - Pyogenic hepatic abscess: results of current management.
AB  - From 1980 to 1991, 56 cases of pyogenic liver abscess were treated at the
      Cleveland Clinic. The most frequently used treatment was percutaneous catheter
      drainage of the abscess under computed tomography (CT) guidance (39 patients),
      followed by CT-guided aspiration without catheter drainage (10 patients). Six
      patients were initially treated by open operative drainage; another five were
      operated upon after CT guided drainage had failed. One patient with advanced
      pancreatic cancer was treated with antibiotics only. The overall mortality rate
      was 12.5% (7/56). It is clear that the preferred method of treatment for pyogenic
      hepatic abscess is now CT guided catheter drainage. Operative drainage is
      reserved for patients who fail to respond to percutaneous drainage or in whom
      surgery is indicated for other purposes. Aspiration without catheter drainage is
      a modality that needs further evaluation to define its indications.

PMID- 7733545
TI  - Laparoscopic colon surgery: report of a series.
AB  - A multicenter retrospective study was performed of laparoscopic colon surgery.
      Thirty unselected patients underwent a variety of procedures including right
      hemicolectomy (11), sigmoid and left colectomy (7), takedown of sigmoid
      colostomies (8), low anterior resection (2), AP resection (1), and colotomy (1).
      The conversion rate from laparoscopic to open was 10 per cent. Comparisons were
      made between this group and institutional controls for cost and lymph node
      harvest. Operating technique is discussed. Lymph node harvest was comparable with
      open procedures. Postoperative length of stay averaged 8.3 days. Hospital costs
      were $11,010 compared with an institutional norm of $13,050. Major variations in
      costs were between institutions rather than surgeons or techniques and correlated
      as well with postoperative length of stay. An anatomically equivalent oncologic
      resection was able to be performed with an acceptable morbidity (24%) and
      mortality (0%).

PMID- 7733546
TI  - Physiological effects of liver packing.
AB  - Liver packing for the control of hepatic hemorrhage may compromise patients'
      hemodynamics and oxygenation. We present two cases where there was physiologic
      improvement upon removal of the liver packs.

PMID- 7733547
TI  - Does oxygen delivery-directed resuscitation worsen outcome of head injured
      patients with multisystem injuries?
AB  - There is concern that oxygen delivery-directed resuscitation in patients with
      multiple trauma, including severe head injury, may worsen neurologic recovery. To
      study this, we retrospectively examined 31 patients admitted over an 18-month
      period who met the inclusion criteria of having suffered blunt trauma, were
      between 15 and 65 years of age, had an admission Glasgow coma scale of < or = 8,
      intact corneal and gag reflexes, and extracranial injury with an Abbreviated
      Injury score of > or = 3. All patients were placed on intracranial pressure
      monitors. In comparing the 14 patients whose resuscitation was guided by oxygen
      delivery (DO2) with the 17 who were resuscitated by standard fluid restriction
      (FR), we found that despite the DO2 group's having received a significantly
      greater volume of resuscitation fluids in the first 48 hours after injury, there
      was no difference in the neurologic recovery between the two groups.

PMID- 7733548
TI  - Vena cava resection during post chemotherapy lymphadenectomy for testis tumor.
AB  - Two patients underwent retroperitoneal lymphadenectomy after chemotherapy for non
      seminomatous germ cell testis tumor. A dense desmoplastic tissue reaction between
      the infrarenal vena cava and perivascular lymphatic tissue prohibited removal of
      the nodal packet from the vena cava in both cases. We herein discuss two
      techniques for vena cava resection in these difficult cases.

PMID- 7733549
TI  - Contaminated wounds: the effect of initial management on outcome.
AB  - Delayed primary closure has been advocated as the optimal method of management in
      the presence of wound contamination. The present study was performed to determine
      whether surgeons have accepted this standard. A total of 918 surgical wounds were
      evaluated and classified according to the level of contamination and type of
      wound management used. We found that 150 patients had a Class III or Class IV
      contaminated wound; however, only 21 per cent were treated with delayed primary
      closure. The 118 patients treated with primary closure and antibiotics had an
      aggregate wound infection rate of 27 per cent (Class III-29%; Class IV-24%). Only
      one (3%) of the wounds managed by delayed primary closure developed an infection.
      If infection did not occur, there was no difference in the length of stay between
      patients managed with primary closure and delayed primary closure. However, there
      was a significantly longer length of stay in the primary closure group if
      infection occurred. Benefit risk analysis of the patients with contaminated
      wounds confirmed that in this clinical setting, delayed primary closure remains
      the optimal method of management for the wound.

PMID- 7733550
TI  - Axillary metastasis from occult breast carcinoma: diagnosis and management.
AB  - Axillary metastasis from carcinoma of an unknown primary site is an uncommon and
      difficult problem. When biopsy of an enlarged axillary node reveals
      adenocarcinoma, the most likely site (in a female patient) is the ipsilateral
      breast. From January 1977 to December 1986, 10 patients (eight female, two male)
      were treated at the University of Mississippi Medical Center for axillary
      metastasis from carcinoma of unknown primary. Two male patients (ages 60 and 63)
      were believed to have lung primaries. Both had evidence of distant metastasis at
      initial diagnosis and died 2 and 7 months after presentation. Of the eight women
      (ages 40-72, mean 56.5 years), seven developed breast abnormalities between 6 and
      39 months (mean: 15 months) after initial diagnosis, and two of these underwent
      modified radical mastectomy. No primary site was identified in the eight women.
      Two women had evidence of distant metastases at initial presentation. All
      patients have died with disease at a mean of 42 months (range: 2-93 months). In
      contrast with other reported series, the outcome of patients with occult breast
      carcinoma presenting as axillary adenopathy was not favorable.

PMID- 7733551
TI  - Elderly drivers involved in road crashes: a profile.
AB  - The ability of elderly citizens to drive safely has been the subject of ongoing
      debate. To identify the type of elderly driver who becomes involved in an injury
      producing road crash, we profiled all drivers over 39 years of age admitted to
      our Level I Trauma Center over a 1-year period. Data were prospectively collected
      and drivers age 40-59 years were compared with those over 60 years. Eighty-four
      drivers age > or = 60 and 130 drivers age 40-59 were studied. Of the 84 elderly
      drivers, 67 were deemed at fault. Twenty-four of those crashes were due to
      driving errors, 12 due to syncopes, and in 20 no crash cause was determined.
      Fifty-three of the 67 at fault drivers had significant underlying medical
      problems, compared to 9 of 17 deemed not at fault. Only four were legally
      intoxicated. Of the 130 drivers in the comparison group, only 19 had significant
      underlying medical problems; in three syncope was suspected; 18 were legally
      intoxicated. We conclude from our data that underlying medical disorders occur
      frequently in elderly drivers and may contribute to their incidence of road
      crashes.

PMID- 7733552
TI  - Management of unilateral vocal fold paralysis.
AB  - Management of unilateral vocal fold paralysis continues to generate controversy.
      Polytetrafluoroethylene (Teflon) injection remains the most popular procedure for
      medialization; however, there are problems involved with its use. Endoscopic
      assessment of patients treated with medialization laryngoplasty revealed a normal
      mucosal wave form in contrast to the stiff vocal fold observed with Teflon
      injection. Medialization laryngoplasty is also considered a reversible procedure.
      Based on these findings, medialization laryngoplasty should be considered the
      procedure of choice for unilateral vocal fold paralysis.

PMID- 7733553
TI  - Hepatic resection for colorectal liver metastases.
AB  - The lack of other effective treatment for colorectal liver metastases makes
      hepatic resection a primary treatment consideration. Between January 1980 and
      December 1990, 26 selected patients with liver colorectal metastases who
      underwent hepatic resection were reviewed. The age, sex, site of primary lesion,
      histological grade, lymph node involvement, location, size, and number of hepatic
      metastases, type of hepatic resection, and preoperative CEA blood levels were
      documented. Complete removal with histologically negative resection margins were
      accomplished in 24 patients. The extent of resection performed was hepatic
      lobectomy in 12 patients. Segmentectomy in eight patients, and wedge resection in
      four patients. The 5-year survival rate was 30.5 per cent. Patients with
      metachronous metastases showed a better survival rate than those with synchronous
      lesions--46.6% versus 13.6% respectively (P = 0.08). None of the other factors
      studied showed a significant effect on survival. All patients were followed from
      the time of hepatic resection to the time of this study or death. During a median
      follow-up of 30.9 months, 20 patients developed recurrence of their disease (60
      per cent in the liver). There was no perioperative mortality. Morbidity arose in
      66.6 per cent of patients, with a majority of the complications being minor. We
      conclude that hepatic resection can be performed safely enough to be recommended
      in selected patients.

PMID- 7733554
TI  - Penetrating cardiac wounds: predictive value of trauma indices and the necessity
      of terminology standardization.
AB  - The authors evaluated the usefulness of different trauma indices in the
      prediction of outcome following penetrating cardiac wounds. Sixty-three patients
      were retrospectively reviewed. Age, mechanism of injury, Physiologic Index (PI)
      on admission, site of injury, associated injuries, ISS, RTS, Penetrating Cardiac
      Trauma Index (PCTI), Penetrating Thoracic Trauma Index (PTTI), Penetrating Trauma
      Index (PTI), TRISS and mortality rate were reviewed. There were 34 patients with
      a gunshot wound (GSW) and 29 with a stab wound (SW). Shock was present on
      admission in 88.9 per cent. Mortality was 83 per cent for GSW, 44 per cent for
      SW, and 39 per cent for patients arriving the hospital with measurable blood
      pressure. RTS, PI, PCTI, PTTI, PTI, and ISS reached statistical significance when
      comparing survivors and nonsurvivors. The probability of survival (PS) based on
      the TRISS methodology was 37.84 +/- 5.14. The observed survival rate was 38 per
      cent. Fourteen patients were considered "fatal" on admission and underwent an
      emergency thoracothomy. Mortality rate for this selected group was 100 per cent.
      We conclude that physiologic impairment, shock, and GSW are variables with high
      significance on mortality. Trauma indices such as PI, RTS, PCTI, PTTI, PTI, and
      ISS are good predictors of outcome. Trauma indices are an important tool to
      objectively compare results among different institutions.

PMID- 7733555
TI  - Massive gastrointestinal bleeding caused by Dieulafoy's lesion.
AB  - Dieulafoy's lesion is an anomaly, difficult to diagnose, consisting of an
      abnormally dilated submucosal gastric blood vessel that can cause life
      threatening gastric hemorrhage. Five patients with Dieulafoy's lesion and massive
      gastrointestinal bleeding are described. The diagnosis was made by endoscopy in
      two patients and during operation in the other three. On endoscopy the source of
      bleeding was localized to the stomach in all patients. This information was
      important for the operative approach. Conservative treatment failed to prevent
      rebleeding, and all patients required surgery. In three patients excision of the
      lesion was performed, and suture only in the other two. The difficulties in
      diagnosis of the lesion and the surgical options are discussed.

PMID- 7733556
TI  - Primary renal sarcoma.
AB  - Primary renal sarcoma represents approximately 1 per cent of all primary tumors
      of the kidney. The purpose of this study is to review the experience at Roswell
      Park Cancer Institute with the treatment of primary renal sarcoma. Four patients
      with a diagnosis of primary renal sarcoma admitted from 1976 to 1983 form the
      basis of this review. All patients underwent radical nephrectomy. The tumor was
      localized in two patients, and locally invasive in two patients. All patients had
      recurrence of metastatic disease. Patients with localized disease recurred at
      19.0 and 25.0 months respectively. Patients with invasive disease recurred at 4.0
      and 5.0 months respectively. Patients presenting with localized disease survived
      a mean of 34.0 months. Patients presenting with invasive disease died at 6.0 and
      10.0 months from time of diagnosis. Primary renal sarcoma is a rare entity. Only
      patients presenting with localized disease have a reasonable chance for prolonged
      survival.

PMID- 7733557
TI  - Endoscopic treatment of postoperative hemorrhage from a stapled colorectal
      anastomosis.
AB  - We present the sixth reported case of endoscopic electrocoagulation to
      successfully treat postoperative hemorrhage from a stapled colorectal
      anastomosis. A literature review revealed 17 patients with postoperative
      hemorrhage from a combined total of 775 patients (1.8 per cent) after stapled
      colorectal anastomosis requiring blood transfusion and/or emergency surgery.
      Twelve of the 17 cases involved a circular stapler (71 per cent) used during an
      anastomosis to the rectum (69 per cent). Nonoperative therapy was successful in
      14 of the 17 patients (82 per cent), using endoscopic electrocoagulation in six
      patients (43 per cent) and blood transfusion alone in another six patients (43
      per cent). In follow-up there was one death (cardiac) and two anastomotic
      fistulas (one requiring temporary colostomy) in the nonoperative group. Both
      anastomotic fistulas occurred following hemorrhage from an anastomosis to the
      rectum using the circular stapler, one after endoscopic electrocoagulation and
      the second after blood transfusion alone. In summary, postoperative hemorrhage
      from a stapled colorectal anastomosis, although rare, is most likely to occur in
      a colorectal anastomosis constructed with the circular stapler. Nonoperative
      treatment is usually successful. Endoscopic electrocoagulation may be safely and
      effectively used in the early postoperative period to cease unremitting
      anastomotic hemorrhage.

PMID- 7733558
TI  - Endoscopic basket impaction.
AB  - Endoscopic Retrograde Cholangiopancreatography (ERCP) is an indispensable tool
      for imaging the pancreatico-biliary tree, and in treating diseases of the
      pancreatic and biliary systems. ERCP plays a primary role in the management of
      choledocholithiasis, both in diagnosis and treatment. Complications occur
      infrequently and can usually be treated nonoperatively. An unusual complication
      of ERCP and an impacted stone retrieval basket are presented and discussed along
      with review of the medical literature.

PMID- 7733559
TI  - Dr. Rudolph Nissen: the man and his other contributions.

PMID- 7733560
TI  - [Motor physiopathology of the loop isolated from the small intestine in
      functional reconstructive surgery. Data on the experimental surgical study].

PMID- 7733561
TI  - [The use of defunctionalized loop of the small intestine in esophageal surgery].

PMID- 7733562
TI  - [Use of defunctionalized loop of the small intestine in "total gastrectomy"
      digestive surgery].

PMID- 7733563
TI  - [Roux-en-Y reconstruction with defunctionalized jejunal loop, after gastric
      resection].
AB  - Authors report their personal experience on Roux-en-Y reconstruction, after
      partial gastric resection. They have considered 39 patients: 24 of them had been
      operated for a peptic ulcer of the lesser gastric curve and 15 for a pyloric
      cancer for which a partial gastric resection had been adopted for various reasons
      (age, stage or else). The follow-up lasted on an average of 42 months (4 to 68).
      Controls concerned secretory activity and motility. A prolonged stasis of solids,
      in the gastric stump or in the isolated loop, has been observed in two of the
      long controlled patients, together with superficial ulcers of the digiunal
      mucosa. Alcaline reflux was absent or very small; inflammatory changes of the
      gastric mucosa were hardly evident. In conclusion the authors regard the partial
      gastric resection, followed by the reconstruction with a digiunal isolated loop,
      as a valid surgical technique, for peptic ulcers of lesser gastric curve and for
      gastric cancers for which total gastrectomy seems not indicate.

PMID- 7733564
TI  - [Klatskin's+ tumor: our experience].

PMID- 7733565
TI  - [Use of Roux derivation with excluded loop in inflammatory pancreatopathy].

PMID- 7733566
TI  - [Role of the intestinal neuroendocrine system in the adaptation following
      reconstruction with defunctionalized Roux-en-Y loop or ileal reservoir].

PMID- 7733567
TI  - Ileal pouches: technical aspects of the pouch-anal anastomosis.

PMID- 7733568
TI  - [Anorectal neuroendocrine carcinoma: observations on a case and review of the
      literature].
AB  - Carcinoid tumours of the anorectum are rare (0.7% of malignant rectal tumours).
      Because of this rarity several aspects of the management of these tumours remain
      controversial. Diagnosis may be delayed because of failure to recognize their
      morphological characteristics and histological appearance may not reflect their
      biological behaviour. Immunocytochemistry for neuroendocrine-cells are essential
      to identify different types of carcinoid tumours and to do differential diagnosis
      from other malignant tumours. All that allow an exact therapeutic approach to
      these tumours. The tumours less than cm 1 in diameter can be safely treated by
      local excision; the tumours more than cm 1 in diameter are treated by radical
      surgery (AAP).

PMID- 7733569
TI  - [Perianal Paget's disease: clinical observation and review of the literature].
AB  - The authors present a case of PPD, stressing the importance to distinguish "true"
      PPD from pagetoid spread, for correct diagnosis and appropriate treatment. This
      distinction is possible by using immunohistochemical stains, with particular
      regarding Ab-GCDFP-15, considered specific marker for Paget's cell.

PMID- 7733570
TI  - [Squamous carcinoma of the anal canal and its variations. Personal experience and
      review of the literature].
AB  - Six cases of anal canal squamous carcinoma are presented. The authors precise the
      present view about pathological, epidemiological, clinical and therapeutical
      aspects of these lesions. They stress, also, the primary role of embryology and
      anatomy in the oncogenesis of such tumours; the importance to single out specific
      population at risk, absolutely different from the typical one for rectal
      adenocarcinoma and the role of chemoradiation therapy as treatment of choice of
      these neoplasms. Particular importance is given to modern histologic and
      histogenetic classification of these tumours, stressing the difficulties to
      distinguish the various histologic types.

PMID- 7733571
TI  - [Postanal repair in the treatment of idiopathic neurogenic fecal incontinence].
AB  - Faecal incontinence is an important disabling symptom in the affected patients.
      Classically, we divide faecal incontinence in two main types: traumatic faecal
      incontinence and neurogenic faecal incontinence. Neurogenic faecal incontinence
      is characterized by a diffuse weakness of anal sphincter and of the elevator
      muscles. The aim of the present study was to evaluate the outcome of postanal
      repair procedure in the management of neurogenic faecal incontinence. To this end
      we studied 20 patients with neurogenic faecal incontinence who underwent a
      postanal repair procedure according to the method described by Parks. Mean follow
      up was up two years and was based mainly both on clinical evaluation and
      manometric values carried out on a 6 monthly basis. When the outcome was
      evaluated in terms of faecal incontinence our date were similar to those reported
      by Parks and Keighley. In the subjects studied we haven't reported any major
      complications apart from two cases of wound's infection which were efficaciously
      treated. Our findings supported the view that postanal repair procedure is the
      surgical approach of choice in the patients with idiopathic neurogenic faecal
      incontinence.

PMID- 7733572
TI  - [Surgical choices and approaches in treating tumor metastases].
AB  - In oncology metastatization modifies the prognosis and the quality of life of
      patients. Otherwise metastases are apt to make the surgeon to modify in many
      cases his operative decisions, and moreover means and times of the demolitive
      surgical procedures for curative purpose. Namely the presence of metastases at
      the diagnosis is not necessarily the cause of a refusal for potentially curative
      operations, both for sincrone or methacrone metastases, because there are still
      possible, also if less frequently, the hopes of success, especially if they are
      localized in particular target organs. Actual knowledge about pathogenesis of
      metastases during surgical procedures, induces us to adopt particular caution in
      demolitive operations, to avoid the risk that surgery facilitate their insurgence
      or dissemination. Finally the clinically primitive metastases pose diagnostic
      problems minimally different from what was the current strategy previously. The
      study consider these various facets of the problem, on the basis of personal
      experience and of literature data, and proposes operative protocols that are
      actually generally accepted.

PMID- 7733573
TI  - [Familial neoplasms: investigation of genealogic trees of patients surgically
      treated for colonic adenocarcinoma].
AB  - In order to study the familial aggregation of colorectal cancer we investigated
      the pedigrees of the patients with adenocarcinoma of the large bowel who
      underwent a surgical operation between november 1990 and october 1992 at the
      Istituto di Chirurgia Generale e Sperimentale Of Pisa University. For each
      proband, information was obtained on his/her four grandparents and all their
      second generation descendants. The final sample included 99 probands and 1455
      relatives. Only two cases with diagnosis of familial adenomatous polyposis were
      excluded. As a control group, we applied the same methodology to the spouses of
      probands, collecting in the end a sample of 72 families including 1163
      individuals. The frequency of both colorectal and extracolonic cancer was higher
      in the relatives of cases than in the control group, for all the relationships.
      Among the first degree relatives, the empirical risk of colorectal cancer was
      1/30 among the case families and 1/139 among the control families, for a 4.6 fold
      increase in risk. For cancers at all sites (colorectal excluded), the
      corresponding risk were 1/8 and 1/12. We computed the posterior probability of
      dying from cancer for a random individual, given the known affection status of
      one or more of his/her relatives of specified relationship. For an individual
      with one first degree relative affected by colorectal cancer the posterior risk
      of the same tumor was 1/15, compared to a value of 1/70 for the entire control
      population. Considering all cancers, colorectal excluded, we obtained the result
      that for a person with at least three affected relatives, one of first, one of
      second and one of third degree, the probability of dying from colorectal cancer
      was 6%. The distribution of the number of affected individuals for kindred was
      highly skewed, with a few families responsible of a large part of the observed
      familial aggregation. This was true for both the cases of colorectal cancer and
      for all-site cancer. However, no family fulfilled the criterion of hereditary
      nonpolyposis colorectal cancer (Lynch syndromes I or II).

PMID- 7733574
TI  - [Prognostic value of nuclear morphology in colorectal neoplasms].
AB  - Cytomorphometry measures the main geometric parameters of the cell nucleus (area,
      min. and max. diameter, circunference) on ordinary histological preparations. It
      has been employed to asses the prognosis of breast and ovary tumours. The
      possibility that cytomorphometry, when allied with other parameters, such as age,
      sex, Duke's stage, bleeding etc., can be used in the prognosis of tumours of the
      large intestine is examined through a study of intraoperative biopsies from 44
      patients followed after surgery. Univariate analysis showed that the Duke's stage
      and tumour site were significantly related to prognosis. The standard deviation
      of the maximum diameter and circunference were also related to survival with a
      negative correlation. Multivariate analysis confirmed the significance of the
      maximum diameter and the Duke's stage. These parameters were then used to
      calculate the relative risk. If due account is taken of the reservation expressed
      in the literature concerning the reproducibility of the data offered by
      cytomorphometry and its heavy dependence on the skill of the operator, it can be
      used to advantage in the prognosis of the colorectal tumours.

PMID- 7733575
TI  - [Surgical treatment of pulmonary metastases of primary neoplasms of the
      urogenital tract].
AB  - The authors review the literature data concerning the surgical therapy of
      pulmonary metastases from genital and urinary tumours. In both cases a combined
      chemo-surgical treatment is able to increase longterm survival. Some personal
      cases successfully treated are reported. The case is reported also of a young
      girl operated on for pulmonary metastases from a Wilms tumour. Successively, a
      heart transplantation was performed. She is alive and well.

PMID- 7733576
TI  - [Adrenal metastasis of choroidal melanoma: a case report].
AB  - We report on the case of a 32 years old man submitted to right eye enucleation
      twelve years before for a choroidal melanoma. We observe a metastases located in
      the left adrenal gland. The blood-tests, the TAC of the abdomen did not show
      other localizations, while during laparotomy were discovered metastases in the
      pancreas and in the omentum. In this case, the age of tumor's development, the
      age of clinical manifestation, the period between the enucleation and the
      appearance of the metastases and their localization are exceptions to the normal
      biological behaviour of the choroidal melanoma.

PMID- 7733577
TI  - [Clinical study of residual function and recurrences in patients after partial
      thyroidectomy for non-toxic nodular goiter].
AB  - The different surgical chances for the treatment of non toxic nodular goiter led
      the Authors to study the residual function after partial thyroidectomy. A
      variable rate of recurrences and hormone deficiency was shown in patients who
      underwent sub-total thyroidectomy, lobectomy and enucleation. It depended on the
      amount of residual gland and the different methods they used. Recurrences
      occurred more in patients studied by ultrasonography. After sub-total
      thyroidectomy the Authors noted a more reduced number of recurrences than after
      lobectomy and enucleation. There was a meaningless connection between high
      plasmatic levels of TSH and recurrences. Subclinical hypothyroidism was higher in
      patients who underwent subtotal thyroidectomy than in patients treated with
      lobectomy and enucleation. These clinical data show that recurrences could depend
      on growth factors (EGF, IGF) in thyroid tissues and not only on TSH action.
      Therefore the surgical attitude of the authors in the treatment of nodular goiter
      consists in total thyroidectomy.

PMID- 7733578
TI  - [Boerhaave's syndrome].
AB  - The authors report a personal case of "Boerhaave's syndrome" recovered by
      immediate reconstruction of perforated distal esophagus. They stress the value of
      early diagnosis by using X-ray study of upper gastrointestinal tract and
      immediately surgical treatment, very important for favourable prognosis.

PMID- 7733579
TI  - [Subtotal colectomy with ceco-rectal anastomosis].
AB  - A case of subtotal colectomy cecoproctostomy for multiple lesions of the colon is
      introduced. This procedure has advantages over ileoproctostomy because it spares
      the terminal ileum, ileocecal junction and cecum. Due to the high incidence of
      bowel movements after the ileoproctostomy operation, the authors recommend
      cecoproctostomy as a valid choice in a selectioned group of patients with
      multiple or extended lesions that spares cecum and rectum.

PMID- 7733580
TI  - [Preliminary experience with the surgical treatment of inguinal hernias with the
      Shouldice procedure].
AB  - The authors report their recent experience on the surgical treatment of inguinal
      hernias according to Shouldice Canadian repair, used for the undiscussed
      advantages. The least pre-operational preparation, the early mobilization of the
      patient, the reduction of the hospitalization and the almost total absence of
      relapses, support the application of this technique of which we auspicate a wider
      use.

PMID- 7733581
TI  - [Surgical treatment of varicocele].
AB  - The correlation between varicocele and infertility has been established for many
      years. Authors expose their twelve years experience on surgical treatment of
      varicocele. 213 cases have been treated: 105 had infertility associated to
      varicocele and a microsurgical treatment has been performed. A high legature of
      spermatic vein has been applied to 108 patients with normal spermiogram (the last
      6 by laparoscopic technique). In the case in which there is alteration of the
      spermiogram the microsurgical treatment seems more efficient for the sperm
      quality because it is more valuable in eliminating the venous stasis, and the
      operation Belgrano 1 seems to be the best compared to the others. Correlating the
      treatment efficiency to the simplicity of the application and to the treatment
      expense and reduced morbility we think it is advisable to treat the spermatic
      vein with laparoscopic ligature in patients with normal fertility indexes, even
      on the basis of our recent experience. Physiopathology, economic reasons and
      efficacy have been demonstrated.

PMID- 7733582
TI  - [Herniation of the cecum and ascending colon through Winslow's foramen and the
      lesser omentum. A case report].
AB  - Internal hernia into epiploic foramen is a rare clinical entity, representing 1%
      of all herniae and 8% of internal herniae. We report a peculiar case of internal
      herniation presented during a laparotomy for acute colecystitis where the caecum
      and ascending colon entered the lesser sac through the forame of Winslow and
      reentered the main abdominal cavity through a congenital defect of the lesser
      omentum.

PMID- 7733583
TI  - [A case of ileocecocolic intussusception from cecal carcinoma].
AB  - The authors present a case of ileocecocolic intussusception by carcinoma of the
      caecum. They stress the most peculiar aspects of this condition: rare etiology;
      complete invagination of caecum appendix and ileum; typical clinical presentation
      characterized by variable dimensions of the mass and symptoms not ascribing to
      occlusion, no lesions at endoscopy; evidence of a typical "target mass"
      visualized at T.C.

PMID- 7733584
TI  - [Sugioka rotational osteotomy in ischemic osteonecrosis of the femoral head].
AB  - The treatment of ischemic necrosis of the femoral head depends on the stage and
      the age of the patient. Sugioka's rotational osteotomy is an alternative between
      the different conservative techniques. We have used this technique in 12 patient
      and 13 hips. The mean age of the patients was 31.8 ranging from 20 to 40. In the
      first 4 patients we performed the classic technique, as described by Sugioka. In
      the rest of the patients we used a DHS to stabilize the rotation and a maleolar
      screw for trochanteric osteotomy. The follow-up ranged between 24 and 67 months,
      average 42.46 months. The main complications were: 1 embolism, 1 trochanteric
      pseudoarthrosis and 1 common personal nerve lesion. The radiologic study showed
      progression in the majority of the cases. Clinical examination was performed
      following Merle D'Aubigne criteria pre and post surgery. We found 1 excellent
      result, 3 good, 3 fair and 6 poor (four of them needed a T.H.R.). Based on our
      experience, we have suggested a protocol for the treatment of ischemic necrosis
      of the femoral head. We believe that Sugioka's osteotomy can be indicated in
      patients younger than 50 and with less than 200 degrees affected (Stage III). The
      modifications we have made may be useful to achieve a better stabilization of the
      osteotomy and to improve the postoperative period. We have observed an
      improvement in the pain and gait in 60% of the patients. The radiologic study
      showed a progressive deterioration but there was no correlation between the
      clinical and radiological findings. Sugioka's technique allows the preservation
      of the femoral head delaying the total hip replacement.

PMID- 7733585
TI  - [Teaching of laparoscopic surgery. Proposals of the French College of General,
      Visceral and Digestive Surgery].

PMID- 7733586
TI  - [Place of videosurgery in the treatment of abdominal digestive cancers].

PMID- 7733587
TI  - [Direct colo-anal anastomosis with or without a reservoir].

PMID- 7733588
TI  - [Complications of celioscopic cholecystectomy in 2006 patients].
AB  - The development of laparoscopic cholecystectomy is only justified if it can
      ensure the good results obtained by laparotomy. The purpose of this work is to
      study all complications which occurred in a homogeneous group of patients. From
      May 1988 to January 1993, we operated on 2006 patients by laparoscopy (724 men
      and 1282 women) with a mean age of 50.6 years. Signs of stones in the common bile
      duct were noted in 4.1% and acute cholecystitis was detected in 12.5%. A
      conversion to normal laparotomy was necessary in 2.1% of patients. All
      complications were systematically investigated restrospectively in any patient
      hospitalised for more than five days. Residual stones in the common bile duct
      were not taken into consideration when they were not complications obviously
      related to the operation. We observed five intraoperative complications (4
      hemorrhages, 1 ileum puncture) and 40 postoperative complications (25 non biliary
      and 15 biliary). The 25 non biliary complications consisted of: 1 death by
      pulmonary embolism, 9 hemorrhages, 4 cases of acute pancreatitis, 4 subphrenic
      abscesses, 2 colon punctures, 2 parietal complications, 1 ulcer perforation, 1
      myocardial infarction and 1 phlebitis. The 15 biliary complications consisted of:
      3 lateral punctures of the common bile duct, 9 fistulas of the cystic duct (4
      with a residual stone in the common bile duct and 5 without), 2 punctures of an
      abnormal right hepatic duct, one of which was treated by "Roux en Y loop"
      intestinal diversion, and a late stenosis of the common bile duct.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7733589
TI  - [Argument for choledochostomy, intraoperative endoscopy and external biliary
      drainage in the treatment of lithiasis of the common bile duct. A 15-year
      experience].
AB  - The treatment of common bile duct stones is controversial. The objective of our
      study was to report the results of choledochotomy, rigid choledochoscopy and
      systematic external biliary drainage in the treatment of stones of the common
      bile duct. Over a 15-year period, 555 patients were operated in our department
      according to a precise surgical protocol. 14% of these patients were operated as
      an emergency and 11.8% were operated immediately after endoscopic sphincterotomy.
      One third of patients suffered from cholangitis. The endoscopic investigation of
      the common bile duct was positive in 81.5% of patients. The investigation was
      negative in 18.5% and negative choledochotomy was significantly more frequent in
      patients operated for acute pancreatitis (p < 0.05). External biliary drainage
      was performed in 95.7% of patients. When necessary, a bilioenteric anastomosis
      (3%) or a surgical sphincterotomy (1.9%) was also performed. The postoperative
      mortality rate was 4.8% significantly higher in patients over the age of 70, in
      patients operated as an emergency and in patients operated immediately after
      endoscopic sphincterotomy (p < 0.05). The morbidity rate was 8.4%. Residual
      stones were diagnosed in 4.4% of the patients. The presence of residual stones
      was significantly more frequent in patients with multiple stones of the common
      bile duct (p < 0.05). Long-term follow-up was available for 89% of patients, 95%
      of whom were asymptomatic. These results, based on a homogeneous therapeutic
      protocol, can be used as a reference for the evaluation of other techniques,
      especially endoscopic and laparoscopic techniques.

PMID- 7733590
TI  - [Results of unilateral adrenalectomy for primary hyperaldosteronism].
AB  - From 1970 to 1992, 57 patients underwent unilateral adrenalectomy for primary
      hyperaldosteronism. All were hypertensive and the biochemical profile was
      diagnosed in all cases but two. 44 out of 57 were operated on using to the
      posterior Young Mayor approach. The present series included 44 macroadenomas > or
      = 1 cm in diameter (21 > 2 cm; 23 < or = 2 cm), 7 microadenomas (< 1 cm), 3
      associations of macro and microadenomas and 3 cases of unilateral hyperplasia.
      All were biochemically cured. 4/57 patients remained hypertensive postoperatively
      (3/44 macroadenomas and 1/3 unilateral hyperplasia). There were two late
      recurrences, which were both clinical and biochemical (2 macroadenomas < or = 2
      cm), and one of these was reoperated on for contralateral multiple "adenomas".
      Pathological background was defined by preoperative imaging studies with a
      sensitivity of 100% for MRI (23 cases), 96% for CT-scan (52 cases), 73% for NP 59
      scanning (15 cases), 38% for sonography (16 cases) and 85% for venous sampling (7
      cases). Cure of hyperaldosteronism or hypertension after unilateral adrenalectomy
      was therefore not predictable by the pathological background. If a firm diagnosis
      of primary hyperaldosteronism has been made and the unilaterality of the disease
      has been established, the patient should be operated. Even adrenalectomy for
      unilateral hyperplasia can lead to cure, and the syndrome can recur after removal
      of a solitary macroadenoma.

PMID- 7733591
TI  - [Failure of the treatment of eventrations and hernias with the PTFE plate (111
      cases)].
AB  - Patch repair using a PTFE prosthesis was performed in 111 patients over a 5-year
      period for treatment of incisional hernias (64 cases), inguinal hernias (41
      cases, including 29 recurrences), umbilical hernias (4 cases), epigastric hernias
      (2 cases), lumbar hernias (1 case) and abdominal wall defects after resection for
      endometriosis (2 cases). The surgical technique was limited to simple patch
      closure of peritoneomuscular defects without myoplasty. Follow-up was evaluable
      for every patient and 84 cases have been reviewed clinically by 2 surgeons. 83
      patients (86 patches) were followed for at least 1 year (74.8%). Post operative
      mortality was nil. Morbidity was 17.5% (20 cases, including 14 hematomas, 2
      intraperitoneal bleedings, 3 cases of local sepsis, 1 hydrocele). Recurrence rate
      was 42.2% for incisional hernia repair (27 cases) and 14.6% after inguinal hernia
      repair. Three out of 4 umbilical hernias and 1 out of 2 epigastric hernias
      recurred. 14 patients underwent reoperation for recurrent hernia (11 incisional
      and 3 inguinal). Absence of fibrotic reaction around the PTFE prosthesis was
      noted in every case and appeared to be the main factor of recurrence. Our
      experience suggests that patch technique with PTFE prosthesis should be abandoned
      for the repair of abdominal wall defects.

PMID- 7733592
TI  - [Resection anastomosis of the small intestine by celioscopy in swine. Comparative
      experimental study between manual and mechanical anastomosis].
AB  - Laparoscopic intestinal anastomosis is not very reliable and needs to be evaluate
      in an experimental model in animals before being performed in man. The purpose of
      this study was to evaluate the feasibility, efficacy and safety of manual
      anastomosis comparatively to the standard stapling suture. Twenty female pigs
      weighing 20 +/- 5 kg. were used for this study. A 5 cm ileal segment resection
      was performed under laparoscopy. The animals were assigned to 2 groups. Group I:
      10 animals underwent end-to-end hand-swen anastomosis with Polyglactin 910, dec
      1.5. Group II: 10 animals underwent side-to-side anastomosis using the Endo
      stapler. Operating time and anastomosis time were compared using the Mann-Whitney
      test for statistical analysis. On the 15th postoperative day, the animals were
      sacrificed and the anastomoses were evaluated. There was no operating death in
      the 2 groups. The operative time was significantly longer in group I than in
      group II (p < 0.01), with 180 +/- 40 min vs 49 +/- 25 min respectively. This
      difference was due to the anastomosis time of 130 +/- 40 min vs 16 +/- 6 min
      respectively (p < 0.01). There was 1 postoperative death related to fistula and
      peritonitis in group I and none in group II. The post-operative follow-ing showed
      5 anastomotic leakages (4 in group I and 1 in group II) and 2 relative stenoses
      in group I. This study shows the simplicity and rapidity of performing stapling
      intestinal anastomosis under laparoscopy. Hand-sewn anastomosis is technically
      more difficult to perform under laparoscopy and requires a greater experience.

PMID- 7733593
TI  - [Place of celiosurgery in the extensive diagnosis of gynecologic cancers].
AB  - Laparoscopic surgery occupies an increasingly important place in the diagnosis
      and staging of gynaecological cancers. It allows repeated complete investigation
      of the abdomen and retroperitoneum: macroscopic examination of the peritoneum,
      cytology, biopsies, infracolonic omentectomy, appendicectomy, pelvic and para
      aortic lymphadenectomy, without interfering with therapeutic procedures (simple
      or radical hysterectomy) which can be associated. In cancers of the endometrium,
      it is part of a surgical strategy associating vaginal hysterectomy. In ovarian
      cancers, it is essentially applied to restaging of insufficiently explored
      apparent stage I tumours. In operable cervical cancer, it guides the therapeutic
      protocol and surgical indication by allowing interiliac lymphadenectomy. In
      advanced cervical cancers, it is used to detect para-aortic lymph nodes.

PMID- 7733594
TI  - [Papillary and cystic tumor of the pancreas].

PMID- 7733595
TI  - [Colloid cancer of the rectum revealed by peritonitis caused by perforation].

PMID- 7733596
TI  - [Inguinal hernias in adults. Laparoscopic surgery versus the Shouldice method.
      Controlled randomized study: 181 patients. Preliminary results].
AB  - 181 patients have been included in a controlled randomized prospective study to
      compare two hernia repair technics: Classic al Shouldice herniography vs totally
      pre-peritoneal video-surgery. There was no mortality and no difference concerning
      morbidity, operating time and hospital stay. Videosurgery allows detection and
      treatment of some bilateral hernias not diagnosed by clinical exam, ensures
      better post-operative comfort and has a significant effect on the time to return
      to work (12.5 vs 24.3 days). There was no recurrence in either group with a 12
      month follow-up. These patients must be followed for a long time to compare their
      late results with those of conventional technics.

PMID- 7733597
TI  - [Cytopuncture: an alternative to pelviscopy in the diagnosis of lymphatic
      metastases of urologic pelvic tumors].
AB  - 119 patients with prostatic or vesical tumours without metastases were studied by
      lymphography-aspiration cytology to detect lymph node metastases. 12% of
      aspiration cytologies were uninterpretable, corresponding to N-patients. 12% of
      the 105 interpretable cases were positive. Some of the patients with negative
      biopsies were treated nonsurgically. 28 bladder tumours were treated
      intravesically. 11 prostatic cancers were treated by radiotherapy and 63 patients
      underwent surgical resection. These 63 patients had an interpretable aspiration
      cytology and surgical control. Aspiration cytology was falsely negative in 7
      cases: 4 microscopic metastases and 3 macroscopic metastases. The sensitivity of
      aspiration cytology after lymphography is 66% and its specificity is 100%. The
      positive predictive value is 100% and the negative predictive value is 92.3%.
      These 7 false-negative results included 3 macroscopic metastases already
      identified on CT scan and 4 micrometastases in which surgical resection was
      legitimate.

PMID- 7733598
TI  - [Surgical treatment of genito-urinary prolapses by abdominal approach. Results in
      a continuous series of 203 operations].
AB  - A series of 203 abdominal operations for correction of genital prolapse performed
      between 1985 and 1992 is reviewed. We performed abdominal sacral colpopexy
      systematically associated with a Burch retropubic uretropexy. Resection of the
      peritoneum of the pouch of Douglas, and myorraphy of the levator ani were
      performed according to the findings of the clinical examination. 94 patients
      underwent a sacral colpopexy using a single suture of the cervix to the
      promontory, 41 had an anterior mesh, 33 had a suture associated with an anterior
      mesh, and 35 had 2 meshes (anterior and posterior). 96% of the patients were
      between 41 and 65 years old, and 90% were perimenopausal. 78.6% were multiparous
      and 32% had a neonate weighting 4kg or more. Urinary stress incontinence was
      isolated in 38%, and associated with another disorder in 57.8%. Urodynamic
      studies revealed detrusor instability in 12.3% of patients, and sphincter
      incompetence in 15.2%. Urinary tract insection was the most frequent
      postoperative complication (61.5%). One month post-surgical evaluation showed
      good anatomic results in 94.2 to 100% of cases, and good functional results in 56
      to 70.5%. The longterm results were anatomically good in 86.7 to 100% of the
      patients, and functionally good in 53.3 to 80.5% (mean follow-up = 32.5 months).
      Results were not significantly different between the 4 surgical procedures.

PMID- 7733599
TI  - [Open fractures caused by gunshot in civilian practice. Apropos of 31 cases].
AB  - The authors report their experience of the treatment of 31 gunshot open fractures
      in civilian practice. The fractures, comminuted in two thirds of cases, were
      produced by various fire-arms. Two vascular injuries were observed. Conservative
      treatment was performed in 80% of cases. 13 septic complications were observed (6
      superficial and 7 deep infections). The were also 7 cases of delayed union, 3 mal
      unions and 7 cases of joint stiffness. To improve the prognosis of these lesions,
      the authors emphasize that surgeons must be familiar with ballistic wounds and
      carry out an early initial and appropriate treatment.

PMID- 7733600
TI  - [Circulatory arrest after splanchnic neurolysis with phenol in unresectable
      cancer of the pancreas].
AB  - One of the treatments for pain in patients with unresectable pancreatic cancer is
      chemical splanchnicectomy by phenol. We report two cases of severe cardiac
      arrhythmia followed by circulatory arrest, during intraoperative chemical
      splanchnicectomy. The cardiac toxicity of phenol is known in plastic surgery
      (face peeling). The reasons for this toxicity are not well known. We recommend
      that phenol be replaced by alcohol during chemical splanchnicectomy, because of
      its safety.

PMID- 7733601
TI  - [Non occlusive mesenteric ischemia: a late complication of cardiogenic shock].
AB  - The case of a diabetic 62-year-old man with a past history of myocardial
      infarction, developing a cardial arrest followed by successful cardiopulmonary
      resuscitation, is reported. In the late clinical course, the patient displayed
      abdominal signs related to mesenteric ischaemia. The pathophysiology of non
      occlusive mesenteric ischaemia is discussed. Risk factors such as diabetes,
      cardiovascular disease, hemodialysis, the use of digoxine or alpha-adrenergic
      drugs are listed. Non-occlusive mesenteric ischaemia is not an infrequent
      complication of cardiac failure in high risk patients.

PMID- 7733602
TI  - [Has celioscopy modified the indications for cholecystectomy?].

PMID- 7733603
TI  - [Anal surgery in Crohn disease].
AB  - For twenty years, opinions concerning local surgery of anal lesions in Crohn's
      disease have changed in practice and in the literature. We have reviewed 209
      patients, usually in remission of disease, with at least 6 months' follow-up, who
      underwent local surgery for various anal lesions from 1974 to 1992. In this
      study, our indications and results are discussed and compared to the literature.
      Results of partial haemorrhoidectomy are successful. In anorectal stenosis, with
      rectal involvement, surgery improves the symptoms and can avoid or delay
      proctectomy. Results of surgery for simple fistulas appear to be identical in
      cases with or without Crohn's disease. In complex and suprasphincteric fistulas,
      seton management improves chronic suppuration, occasionally cures the lesion and
      reduces the number of tracts. After seton drainage, transanal rectal advancement
      flaps can be performed, but the results of this procedure have yet to be
      confirmed.

PMID- 7733604
TI  - [Liver transplantation with preservation of portacaval flow: comparison with the
      conventional technique].
AB  - A modified technique of liver transplantation was used in 46 adults. This
      technique consisted of: a) construction of a temporary end-to-side porto-caval
      shunt, b) total hepatectomy with preservation of the inferior vena cava, c)
      closure of the graft inferior vena cava at both ends, d) partial clamping of the
      recipient's inferior vena cava followed by side-to-side cavocaval anastomosis, e)
      suppression of the temporary porto-caval shunt with completion of the operation
      according to the conventional technique. The results obtained with this technique
      were compared to those of 40 transplantations performed with the conventional
      technique. The use of veno-venous extracorporeal circulation was able to be
      avoided in every case with the modified technique, but was necessary in 70% of
      cases with the conventional technique. A significant reduction of the operating
      time (7.2 vs 9.3 hours) and transfusional requirements (11.4 vs 20.3 units of
      packed cells) was observed. The principal characteristic of this technique was
      the haemodynamic stability of the patients throughout the operation. These
      results suggest that this technique is an reliable and effective alternative to
      the use of veno-venous extracorporeal circulation during liver transplantation in
      adults.

PMID- 7733605
TI  - [Liver transplantation with preservation of the inferior vena cava and
      "piggyback" reimplantation of the liver].
AB  - A modified technique of orthotopic hepatic transplantation with inferior vena
      caval preservation and piggy-back procedure is described. This procedure, used in
      14 patients, avoided the need for temporary vena cava clamping in nine cases and
      reduced the need for venous bypass during orthotopic liver transplantation. The
      indications, results and advantages of this procedure are described.

PMID- 7733606
TI  - [Preservation of portacaval flow in liver transplantation: a technical progress
      originating from hepatic surgery].

PMID- 7733607
TI  - [Implantable insulin pump: the first step towards an artificial pancreas].
AB  - Recent improvements in miniaturization of implantable pumps and the ability of
      their control by teletransmission allow implantation of autonomous pumps which
      administer insulin into the peritoneal cavity. Fifty-six patients with diabetes
      mellitus underwent implantation of 66 pumps with a mean function life of 21.8
      months per patient. No patient has died to date. Tolerance of implanted
      components was good. Morbidity was limited to local events, in this series 4
      cutaneous erosions, two of them leading to final pump explantation. Mean global
      blood-sugar, pre- and post-prandial blood-sugar, and glycosylated hemoglobin
      assays were all lower versus pre-implantation assays. A statistically significant
      difference was demonstrated regarding mean global blood-sugar. The frequency of
      severe hypoglycemia incidents (2 in our series) and biochemical hypoglycemia
      (blood-sugar < 65 mg/100 ml) was decreased, representing a major benefit of the
      technique. The patients well-being and quality of life were notably improved.
      Implantable insulin-pump may be offered as alternative treatment to conventional
      insulin-therapy, especially in cases of diabetes which are difficult to control
      and particularly in cases with frequent hypoglycemic malaise.

PMID- 7733608
TI  - Konstantin Konik--a great Estonian surgeon, statesman and freedom fighter.
AB  - The author of this review had the honour of delivering the First Konik's Lecture
      in the Joint Meeting of the Estonian Surgical Association and the Finnish
      Surgical Society on 12th May 1994 at the Sakala Centre, Tallinn, Estonia. In the
      introduction of this lecture the personal history of Konstantin Konik, a great
      Estonian surgeon, statesman and freedom fighter, was highlighted.

PMID- 7733609
TI  - Prevalence of hepatobiliary dysfunction in patients with ulcerative colitis.
AB  - The aim of this study was to estimate the prevalence of hepatobiliary dysfunction
      in a regional unselected group of ulcerative colitis (UC) patients. Five hundred
      and thirty-four patients were included in this study. Eighty-one per cent of them
      had never had abnormal alkaline phosphatase (ALP) values and 72% no abnormal
      alanine amino-transferase (ALAT) values. Thirty patients (6%) had had ALP values
      more than twice the normal (> 550 U/L) at least once during their disease.
      Furthermore, 24 (34%) out of 70 patients with routine liver biopsy at colectomy
      had changes in their liver histology, 13 (19%) of these also having ALP and ALAT
      values within normal range. Primary sclerosing cholangitis (PSC) had been
      diagnosed in 11 (2%) patients. All but one of the PSC patients had had ALP and
      ALAT values more than twice the normal. Almost 30% of all patients had had
      abnormalities in their liver biochemistry at least once during their disease.
      Normal liver biochemistry did not seem to exclude changes in liver histology.
      Although minor hepatobiliary dysfunction is common in patients with UC, more
      serious conditions such as PSC were found to occur in only 2% of patients.

PMID- 7733610
TI  - Cost effectiveness of preoperative ultrasound in primary parathyroid surgery.
AB  - A prospective, randomized, blind study was undertaken to assess whether
      preoperative ultrasound (US) localization of the abnormal parathyroid glands is
      cost-effective in patients undergoing initial neck exploration for primary
      hyperparathyroidism (PHPT). Twenty-eight patients were randomly allocated into
      two groups. In Group I the results of preoperative US were reported to the
      surgeon before exploration, and in Group II he was not informed of the US
      results. All patients underwent bilateral neck exploration, performed by the same
      surgeon. The operating room time was recorded and the operating room costs
      calculated. They included the total costs of cervical US in Group I. The cure and
      morbidity rates in Group I were 100% and 14% and those in Group II 86% and 7%,
      respectively (P > 0.05). The mean operating room time of 97 +/- 15 min in Group I
      was significantly lower than that of 113 +/- 23 min in Group II (P < 0.05). The
      mean operating room costs, however, were almost the same in both groups being
      only 286 FIM higher in Group II (P > 0.4) because the costs of preoperative US,
      the least expensive of the localization studies, of 497 FIM negated any cost
      savings achieved by the reduced operating room time. We thus conclude that
      preoperative US before initial neck exploration for PHPT is not cost-effective.

PMID- 7733611
TI  - Percutaneous interstitial laser hyperthermia in clinical use.
AB  - Twelve patients were treated with laser-induced hyperthermia. Eight had liver
      metastases from breast cancer or colorectal cancer, and four were treated for a
      primary tumour, two in the liver, one in the biliary tract and one in the
      pancreas. The mean diameter of the metastases was 2.5 cm and of the primary
      tumours 4 cm. One patient was given ethanol injections before the treatment, and
      seven were treated with chemotherapy before and two after the treatment. At the
      time of writing this report, all the patients are still alive. The follow-up
      times vary from six months to five years. Treatment was technically possible in
      all cases. The smallest metastasis disappeared totally and, with the exception of
      a few larger tumours, they were reduced in size. There were no serious
      complications. The patients were treated percutaneously under ultrasonographic
      imaging in real time. Only minor side effects were seen, and the method is safe.
      Technically, laserthermia is easy to perform. A skillful radiologist is needed,
      and the presence of an anaesthetist makes it possible to safely treat tumours
      that can be reached only when respiration is controlled mechanically. Controlled,
      randomized studies are now needed to evaluate the method in comparison with other
      palliative treatment modalities.

PMID- 7733612
TI  - Blood and crystalloid cardioplegia in aortic valve surgery.
AB  - Eighty-six patients who had undergone aortic valve surgery were reviewed. Forty
      three had received crystalloid cardioplegia, the other 43 blood cardioplegia.
      Spontaneous beating after cross-clamp release (blood 11; crystalloid 0; P <
      0.001), number of defibrillations (blood 2.1 +/- 2.6; crystalloid 3.8 +/- 2.2; P
      < 0.01) and CK-MB values on the operation day (blood 65 +/- 55, crystalloid 112
      +/- 73; P < 0.001) and on the following day (blood 53 +/- 43, crystalloid 96 +/-
      98; P < 0.01) indicated that blood is a better cardioplegic vehicle for patients
      with hypertrophied hearts.

PMID- 7733613
TI  - Demonstration of a bioactive elastin-derived peptide (Val-Gly-Val-Ala-Pro-Gly) in
      vascular lesions characterised by the segmental destruction of media.
AB  - An antibody to elastin-derived chemotactic peptide Val-Gly-Val-Ala-Pro-Gly was
      used to study human artery samples from 18 patients with various vascular
      lesions, such as aneurysms or occlusive arteriopathy. The antibody recognised
      epitopes in two artery specimens, one occlusive arteriopathy and one aneurysm,
      and both specimens were also characterised by a segmental destruction of media.
      The positive staining for the peptide was located in the elastic membranes and
      endothelial cells that were also stained with antibodies to IgG. This study
      suggests that elastin-derived chemotactic peptides may have a role in vascular
      lesions characterised by a destruction of media and a formation of aneurysm.
      Since elastin-derived chemotactic peptides are more chemotactic to monocytes than
      to neutrophils, it is possible that mononuclear phagocytes are involved in the
      segmental destruction of elastin.

PMID- 7733614
TI  - Copper and zinc concentrations of abdominal aorta and liver in patients with
      infrarenal abdominal aortic aneurysm or aortoiliacal occlusive disease.
AB  - It has been suggested that low copper concentrations in tissues could be a risk
      factor in the development of infrarenal abdominal aortic aneurysms (AAA). To
      further elucidate this argument, liver and abdominal aortic specimens were
      obtained from 19 patients with an AAA and 26 patients with aortoiliac occlusive
      disease (AIOD) during an operation. After tissue breakdown and liquefaction, the
      samples were tested for copper and zinc with atomic absorption spectrophotometry.
      The mean aortic copper level was 3.8 (microgram/g dry weight) in the AAA-group
      and 3.2 in the AIOD-group. The liver copper values were 27.7 and 25.9
      respectively. The zinc concentrations in AAA- and AIOD-groups were 61.1
      (microgram/g dry weight) and 62.8 for the aortas and 207.9 and 191.7 for liver
      specimens, respectively. There were no statistically significant differences
      between the two groups regarding the copper and zinc concentrations found in the
      aorta or liver specimens. On the basis of our findings, it seems unlikely that
      copper and zinc in the aortic wall or in the liver would play an important role
      in the pathogenesis of infrarenal abdominal aortic aneurysms.

PMID- 7733615
TI  - Treatment of priapism: primary results and complications in 207 patients.
AB  - Priapism is a rare disease that has been treated both by conservative methods and
      surgically. Its incidence has increased during recent years because of the use of
      vasoactive drugs for the treatment of impotence. Data on 207 patients treated for
      priapism in 1973-1990 were collected from Finnish hospitals in order to study the
      primary results and complications of different treatment modalities. The material
      was divided into two nine-year periods. Only nine out of 79 patients treated
      conservatively (11%) gained relief from priapism, whereas surgery was successful
      in 59% of cases. The duration of symptoms before hospitalization had shortened
      during the years and surgical procedures had become more popular, with improved
      results. Priapism caused by the injection of vasoactive drugs or priapism of
      short duration caused by some other mechanism was treated successfully with
      aspiration and the injection of sympathomimetic drugs. Nearly all cases of
      priapism of duration of less than four days were treated successfully with small
      shunts. The most common complications were infections, but these could be
      prevented with prophylactic antibiotics. Aspiration and injection of
      sympathomimetic drugs can be recommended as the primary treatment for priapism,
      and if this fails, small shunts. Prophylactic antibiotics are necessary.

PMID- 7733616
TI  - Sonography of Achilles tendon correlated to operative findings.
AB  - Ultrasound examination (US) with a 5 MHz linear array probe was used to examine
      30 patients (34 Achilles tendons) with overuse injuries. The results were
      compared with surgical findings in all cases. Most of the patients had two or
      more sonographical findings. In this study US had an overall sensitivity of 0.96
      in the detection of Achilles tendon pathology. Partial Achilles tendon rupture
      was suspected in ten tendons. During an operation ruptures were found in eleven
      tendons, of which two were fibrotic scars. Changes in inflammatory tendopathy
      (tendinitis, paratenonitis and paratenonitis with tendinosis) were found by US in
      28 tendons and in the operation in 27 tendons. US showed tendinitis in 21 cases,
      of which four had a positive operative finding. In the seventeen negative cases,
      the surface of the tendon looked normal during the operation. Most of these cases
      (14 out of 17) were classified as paratenonitis during the operation. In three
      cases, paratenonitis with tendinosis was classified as paratenonitis in the
      operation and in one case the findings were similar in US and in surgery. US was
      underdiagnostic in paratenonitis and overdiagnostic in tendinitis. Bursitis was
      detected during the operation in ten cases, but only in three cases by US. False
      positive bursitis was diagnosed three times in US compared to the operative
      finding. In chronic bursitis, the bursa can be small, thickened by its wall and
      undetectable by US. High-resolution sonography is a relatively reliable
      diagnostic method in Achillodynia and mainly useful as a preoperative study to
      differentiate a partial rupture from inflammatory states.

PMID- 7733617
TI  - The effect of absorbable self-reinforced polyglycolide membrane on metaphyseal
      bone. An experimental study on rats.
AB  - The effect of self-reinforced polyglycolide (SR-PGA) absorbable membranes on
      metaphyseal bone was studied in eighty-seven rats. SR-PGA membranes, 0.15 mm
      thick, were implanted on the femoral metaphyseal bone: on the periosteum, and
      directly on bone after periosteal stripping. In a control group, only periosteal
      stripping was performed. The rats were killed after 1, 3, 6, 12 and 24 weeks.
      Fibrous tissue formation around the implant, periosteal thickening and new bone
      formation occurred more extensively when SR-PGA membranes were implanted directly
      on bone after periosteal stripping. Fibrous tissue invaded the membranes. At
      twenty-four weeks, few fibre remnants were found embedded in a rim of fibrous
      tissue. No locally adverse reactions were recorded. Polyglycolide (PGA) appeared
      to have a positive inductive effect on new bone formation.

PMID- 7733619
TI  - The establishment of a macrophage-like cell line (Ymnu) from NMRI mice treated
      with N-methyl-N-nitrosourea. II. Induction of differentiation of Ymnu cells: a
      cytochemical and immunocytochemical study.
AB  - The Ymnu cell line established by us from peritoneal exudate cells of mice
      treated with methylnitrosourea is of macrophage origin. We have shown that 54% of
      these cells possess Fc-gamma receptors and can bind opsonized erythrocytes; 30%
      of these cells express the nonspecific esterase and 65% the Mac-1 antigen,
      indicating these cells are dedifferentiated. Treatment of the cells with various
      differentiation inducers led to time-dependent redifferentiation of the cells.
      The expression of the nonspecific esterase increased to 51.1% (TPA), 42.5% (RA),
      63.6% (DMSO), 40.6% (SB). The fraction of Mac-1 positive cells increased to 90.5%
      (TPA), 80.6% (RA), 84.5% (SB) and decreased to 52.7% (DMSO). The maximal effects
      of the chemicals on expression of these two parameters were achieved at different
      times following treatment. While RA and SB were effective after one day, the
      maximum effect of TPA was seen at day 5.

PMID- 7733618
TI  - Heterotransplantation of primary and established human tumour cells in nude mice.
AB  - Previous successful transplantations of human tumour cells into athymic nude mice
      have been described when cells were injected with a reconstituted basement
      membrane (matrigel). We have compared the development and the histology of
      tumours following injection with matrigel or with culture medium of a panel of
      tumour cells exhibiting different degrees of tumorigenicity. Two cell lines (MCF7
      and MCF7/6) required matrigel in order to form tumours. When inoculated with
      matrigel, all the other cell lines tested [MCF7 gpt, MCF7ras, MCF7(AZ),
      MCF7(AZ)TD5, MDA-MB 231, HT1080] showed increased tumour take and reduced latency
      period. Human primary tumours (melanoma, breast and colon cancers) were
      transplanted successfully into nude mice, in the presence of matrigel. Breast
      primary tumours or cell lines gave rise to poorly differentiated carcinomas. The
      other tumours presented histopathological patterns typical of differentiated
      human cancers.

PMID- 7733620
TI  - Rhodamine 123: is it an appropriate dye to study P-glycoprotein activity in
      adriamycin-resistant K562 cells?
AB  - The ability of the P-glycoprotein to efflux rhodamine 123 and adriamycin was
      evaluated using adriamycin-sensitive and -resistant human leukemia K562 cells. We
      observed that low temperature or verapamil (a P-glycoprotein blocker) inhibited
      adriamycin efflux in multidrug resistant cells. In the same conditions, resistant
      K562 cells did not significantly retain rhodamine 123. This dye was located in
      the cytoplasm of resistant cells and did not display spectral properties
      characteristic of stacked rhodamine 123 molecules in mitochondria of sensitive
      K562 cells. Thus, in adriamycin-resistant K562 cells, the rhodamine efflux may be
      due to P-glycoprotein activity and also to a nonspecific targeting of dye in
      resistant K562 cells.

PMID- 7733621
TI  - In vivo tumor necrosis factor-alpha as indicator of biologic and clinical
      response to low-dose SC recombinant interleukin 2.
AB  - The effect of low-dose human recombinant interleukin-2 (rIL-2) on the induction
      of secondary tumor necrosis factor-alpha (TNF-alpha) in vivo was studied in 16
      patients with metastatic renal cell carcinoma. In all patients s.c. rIL-2
      resulted in a significant increase in TNF-alpha serum levels within 4 to 8 hours,
      as determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha serum
      concentrations remained elevated up to 24 hours following single s.c.
      administration of rIL-2. Total secondary TNF-alpha release, as assessed by the
      area under the curve (AUC), appeared to be independent of dose distribution of
      rIL-2 (10 million IU rIL-2 q12 hours versus 20 million IU rIL-2 q24 hours). rIL-2
      induced TNF-alpha release was significantly higher in patients who had received
      prior rIL-2 immunotherapy, while steroids resulted in a significant suppression
      of TNF-alpha release. Secondary TNF-alpha release was statistically associated
      with progression-free survival of renal cell carcinoma patients and may be a
      prognostic factor in patients receiving rIL-2.

PMID- 7733622
TI  - Recurrent deletions involving chromosomes 1, 5, 17, and 18 in colorectal
      carcinoma: possible role in biological and clinical behavior of tumors.
AB  - We have employed cytogenetic and restriction fragment length polymorphism (RFLP)
      analysis to identify a full spectrum of cytogenetic and molecular alterations
      associated with initiation and progression of "sporadic" colorectal cancer and
      also to correlate the alterations with biological and clinical behavior of the
      tumors. The study series included 63 colorectal cancers, 47 primary and 16
      metastatic recurrences. Cytogenetic analysis was successful in 48 tumors (76%) of
      which 44 (91%) were abnormal. Of these 44 tumors, clonal abnormalities were
      identified in 43, whereas chromosomes from one tumor were unsuitable for complete
      analysis. Each of these abnormal tumors displayed heterogeneity with regard to
      extent and complexity of recurrent chromosomal abnormalities. Numerical losses of
      chromosomes 17 and 18 (20-34%) and gains of chromosome 7 (28%) were significantly
      higher. The four most frequent structural rearrangements on the other hand,
      involved specific regions of chromosomes 1p, 5q, 17p, and 18q. The shortest
      regions of overlap of these rearrangements or losses were located at 1p36, 5q21
      22, 17p13 and 18q21- > ter. RFLP analysis directed at 1p, 5q, 17p and 18q
      identified allelic deletions of these regions in 39 tumors (64%) which included
      17 normal and 11 cytogenetic failures. Of all the informative tumors, 32%, 37%,
      31%, and 63% showed allelic losses at chromosomes 1p, 5q, 17p and 18q
      respectively. The two methods of analysis (cytogenetics and RFLP) employed to
      identify genetic alterations were complementary; probes for chromosome 1 and 18
      showed the greatest degree of concordance, whereas probes for chromosomes 5 and
      17 provided relatively higher rate of discordance with cytogenetic results. These
      differences could be attributed mainly to three reasons: 1) a limited number of
      probes used for RFLP analysis; 2) contamination of tumor cells with normal cells,
      and 3) either mutational inactivation or deletion of specific alleles not closely
      linked to the probes used. Regardless of these limitations, however, the combined
      use of cytogenetic and RFLP identified genetic alterations in a large number of
      tumors and help elucidate the role of hyperdiploidy and/or relative deficiency of
      a given chromosomal segment in expression of recessive mutations. In addition,
      alterations of either chromosomes 1 or 17 predicted poorer survival for the
      patients with primary colorectal cancer (p = 0.03).

PMID- 7733623
TI  - Quantitative description of morphologic changes effected by antileukemic agents
      in L1210 leukemia cells.
AB  - The effect of antileukemic agents is explained mainly by the inhibition of DNA
      synthesis, which may reflect the structural alteration of the target cells. To
      identify such cellular alterations, in particular morphologic changes associated
      with the exposure to antileukemic agents were investigated in the murine leukemic
      L1210 cell line using flow cytometry and image analysis. Cells were cultured with
      eight kinds of antileukemic agents in cytostatic concentrations which are
      clinically achievable. Living cells were observed in culture without fixation or
      staining. Two parameters related to cell size and shape were measured
      simultaneously by the image analysing computer. These parameters provided us with
      different criteria for characterizing the antimetabolites, DNA-strand-damage
      inducers and other agents tested. Such morphologic studies may make it possible
      to estimate the characteristics of various antileukemic agents.

PMID- 7733624
TI  - Protection by coffee cherry against spontaneous mammary tumour development in
      mice.
AB  - Chronic ingestion of an extract of coffee cherry (CC), the residue left after
      removal of coffee beans, induced a marked suppression of spontaneous mammary
      tumour development in a high mammary tumour strain of SHN virgin mice. The growth
      of normal and preneoplastic mammary glands was also apparently inhibited by the
      treatment. While the treatment resulted to some extent in a decrease of water
      intake and a retardation of body growth, the excretion of urinary components such
      as urea, allantoin and creatinine was increased and serum free fatty acid level
      was decreased by CC. Little modulation of the endocrine system was noted by the
      treatment. Finally, a promising chemopreventive role of CC in tumours is
      indicated.

PMID- 7733625
TI  - Efficacy of immunochemotherapy with Ftorafur and Krestin in rats.
AB  - The effectiveness of combined administration of Ftorafur (FT) and Krestin (PSK)
      on experimentally-induced liver cancer has not been established. This study was
      undertaken to elucidate the effect of combined administration of these drugs on
      tumor growth and temporal changes in the immuno-endocrine system under this
      immunochemotherapy. Male inbred WKA/H strain rats were used. The drugs used were
      FT and PSK, each dissolved in water and fed orally. The drugs were administered
      separately but concomitantly in standardized cycles to the tumor-bearing animals.
      KDH-8 ascitic liver cancer cells were subcutaneously transplanted into WKA rats.
      The tumor growth inhibition rate of FT and PSK was then determined. Twenty-one
      days after subcutaneous transplantation, tumor growth in the combined
      administration transplantation, tumor growth in the combined administration group
      was significantly inhibited, compared to the control group (p < 0.001). At
      fourteen days, plasma ACTH levels of the FT + PSK combined group were
      significantly lower than those of the control group (p < 0.001).

PMID- 7733626
TI  - Recombinant human interferon alpha-2a increases the antitumor activity of 5
      fluorouracil on human colon carcinoma xenograft Co-4 without any change in 5-FU
      pharmacokinetics.
AB  - We investigated the modulating effect of recombinant human interferon alpha-2a
      (IFN-alpha) on the antitumor activity of 5-fluorouracil (5-FU) against a human
      colon carcinoma xenograft (Co-4) in nude mice with reference to changes in the
      pharmacokinetic pattern of 5-FU. Mice bearing Co-4 received 5-FU ip at a dose of
      90 mg/kg once with or without IFN-alpha, which was administered sc at a dose of
      60.000 IU/mouse daily for 7 days before 5-FU treatment. When the area under the
      curve (AUC) and peak plasma concentration (Cmax) of 5-FU with or without IFN
      alpha were measured as pharmacokinetic parameters, the pharmacokinetics of 5-FU
      was not changed by IFN-alpha administration. This result suggests that the
      modulating effect of IFN-alpha on 5-FU does not involve augmentation of 5-FU
      pharmacokinetic parameters.

PMID- 7733627
TI  - Effects of epidermal growth factor and mitogenic pathway inhibitors on rat colon
      cancer proliferation in vitro.
AB  - The proliferative responses of two rat colon cancer cell lines (Per192NR and
      Per237) to concentrations of epidermal growth factor (EGF) were assessed alone,
      or in combination with calcium sequestration or inhibitors of protein kinase A, C
      (PKA and PKC). Up to 160nM of EGF stimulated cell proliferation in Per237 cells,
      but was ineffective in Per192NR cells. In both cell lines all inhibitors failed
      to alter basal proliferation. In Per192NR cells the combination of 5 to 20nM EGF
      and inhibitor resulted in a biphasic reduction in basal proliferation which was
      lost by 20nM. In the Per237 cells only 10nM EGF and PKA inhibitor reduced
      proliferation. Tumours derived from the same origin respond differently to EGF
      induced mitogenesis.

PMID- 7733628
TI  - 5-Fluorouracil cytotoxicity in human colon HT-29 cells with moderately increased
      or decreased cellular glutathione level.
AB  - Little is known whether diet or certain components in the diet can modulate the
      efficacy of 5-fluorouracil (5FU) in patients with colon carcinoma. Glutathione
      (GSH), an important antioxidant and anticarcinogen, is present in many foods in
      varying amounts. This study examined whether a moderately increased or decreased
      cellular GSH level had any effect on the growth of human colon adenocarcinoma
      cells HT-29 and on the cytotoxic activity of 5FU in these cells. GSH and
      buthionine sulfoximine were used to enhance or reduce the GSH level respectively
      in these cells. A 34% increase in cellular GSH level had no effect on the growth
      of HT-29 cells, nor on the cytotoxic activity of 5FU as determined by the MTT
      colorimetric assay and cell counts. A 50% reduction in the cellular GSH level was
      found to enhance 5FU cytotoxicity by 20% to 31% as determined by the MTT
      colorimetric assay, depending on the 5FU concentration. This study shows that a
      moderate change in the GSH level in HT-29 cells had little or no effect on the
      cells' growth, but a decrease in cellular GSH level slightly enhanced the
      cytotoxic activity of 5FU in these cells.

PMID- 7733629
TI  - Are matrix-immobilized neoglycoproteins, plant and human lectins and carbohydrate
      -binding antibodies from human serum mediators of adhesion in vitro for carcinoma
      and lymphosarcoma cells?
AB  - Mediation of cell adhesion by defined molecules can be studied by their
      immobilization onto a nitrocellulose matrix and incubation with cells. In order
      to infer the capacity of deliberately selected protein-carbohydrate interactions
      to establish sugar-inhibitable cell adhesion, a panel of immobilized
      neoglycoproteins was employed for the murine lymphosarcoma lines RAW-117 with low
      (P) and high (H10) metastatic capacity, a human mammary carcinoma line (DU4475)
      and three human colon carcinoma lines (C205, SW480, SW620). Exhibiting an
      otherwise rather similar behavior relative to the line with low metastatic
      potential, the murine line RAW117-H10 bound strongly to the matrix with carboxyl
      group-bearing N-acetylneuraminic acid and glucuronic acid as well as rhamnose.
      Whereas the analysis of carbohydrate-mediated adhesion yielded comparable results
      for the three colon carcinoma lines, a markedly reduced number of adherent cells
      was counted for matrix-attached alpha- and beta-galactosyl, alpha-mannosyl and
      alpha-glucosyl moieties in the case of the mammary carcinoma line, raising
      evidence for cell lineage-dependent alterations of this property. From the
      carbohydrate-binding proteins, the plant lectin, concanavalin A and Viscum album
      agglutinin almost invariably served well as cell adhesion molecules. Appropriate
      cell surface sugar receptors, probed with neoglycoproteins, and glycoconjugates,
      probed with lectins, thus can contribute to adhesion in this model system. The
      immobilized human beta-galactoside-binding lectin (Mr 14kDa) caused adhesion of
      the murine lines and one colon carcinoma line (SW480). Neither C-reactive protein
      under conditions that induce its activity as lectin nor serum amyloid P component
      nor a lactose-binding immunoglobulin G fraction from human serum were reactive.
      However, cell adhesion to the alpha-galactoside-binding immunoglobulin G fraction
      of human serum was seen with the murine line of low metastatic capacity and the
      mammary carcinoma line. Cells of this line adhered also to the mannan-binding
      protein from human serum, supporting the view for its potential role in host
      defence against aberrantly glycosylated tumor cells.

PMID- 7733630
TI  - Exercise, cancer and the immune response of monocytes.
AB  - We examined the influence of a regularly moderate endurance training program on
      qualitative and quantitative alterations of monocytes from 24 breast cancer
      patients. At the beginning, after 5 weeks and 7 months of bicycle training we
      analyzed the composition of leucocytes and phagocytotic activity of monocytes
      using two different methods under resting conditions. At the end of the study the
      amount of granulocytes was enhanced, but lymphocytes and monocytes were
      decreased. While the phagocytotic capacity of monocytes increased compared with
      receptor destroying enzyme-treated sheep red blood cells, phagocytosis against
      Anti D-loaded human erythrocytes did not change. These different results led us
      to suggest that physical exercise training increases the number of specific
      receptors in the surface membrane of monocytes.

PMID- 7733631
TI  - Differentiation induction in the human rhabdomyosarcoma cell line TE-671. A
      morphological, biochemical and molecular analysis.
AB  - In the clonal human rhabdomyosarcoma cell line TE-671-1A, the expression of genes
      implicated in myogenic differentiation was determined before and after exposure
      to the differentiation inducers retinoic acid (RA), sodium butyrate (NaBut) and N
      monomethylformamide (NMF). Exposure to NaBut or RA resulted in a significant
      (NaBut: p < 0.0001; RA: p < 0.05) increase in biochemical differentiation
      paralleled by a significant (NaBut: p < 0.0001; RA: p < 0.0002) inhibition of
      proliferation. An increase in the relative number of myotube-like giant cells was
      observed after exposure to NaBut. Exposure to NMF proved to be least effective
      and produced a significant (p < 0.0001) inhibition of proliferation without
      increase in differentiation. On the molecular level, exposure to RA resulted in a
      moderate increase in RAR a mRNA expression, whereas CRABP mRNA remained constant.
      RAR beta and RAR gamma mRNA were not expressed. mRNA expression of c-raf, c-myc
      and c-Ki-ras remained constant before and after exposure to all inducers of
      differentiation. C-fos mRNA was not expressed. In summary, differentiation can
      successfully be induced in the human rhabdomyosarcoma cell line TE-671-1A by
      various inducers of differentiation. In contrast to other myogenic cell lines,
      however, the proto-oncogenes myc, fos and raf are not involved in the
      transmission of myogenic differentiation signals in TE-671-1A cells.

PMID- 7733632
TI  - Selection of N-(phosphonacetyl)-L-aspartate resistant Chinese hamster mutants in
      the presence of the uridine uptake inhibitor dipyridamole.
AB  - In mammalian cells selected in culture for resistance to PALA the CAD gene is
      amplified and these cells are a widely used model system to study gene
      amplification. Selection of resistant mutants is routinely performed in medium
      supplemented with dialyzed serum, because the cytotoxic effect of PALA is
      reversed by uridine, which is contained in serum. We have shown that in Chinese
      hamster cells dipyridamole reduced uridine uptake to less than 5% with limited
      effect on cell survival. Moreover, in medium supplemented with complete serum and
      10 microM dipyridamole the toxicity of PALA was similar to that obtained in
      medium containing dialyzed serum. We then used 10 microM dipyridamole to inhibit
      uridine uptake during selection of PALA resistant colonies and found that both
      the frequency and the type of mutants were as those obtained in the presence of
      dialyzed serum. In particular, in the five mutants tested, the mechanism of
      resistance to PALA was amplification of the CAD gene.

PMID- 7733633
TI  - Free radical-dependent DNA lesions are involved in the delayed cardiotoxicity
      induced by adriamycin in the rat.
AB  - The role of free radicals in the genesis of adriamycin (ADR)-induced delayed
      cardiotoxicity and the cardioprotective effects of the spin trap N-tert-butyl
      alpha-phenylnitrone (PBN) were investigated in an in vivo rat model. As ADR and
      free radicals are no longer present in the myocardium by the time the delayed
      effects of the drug become apparent, ADR has been proposed to act by causing
      early radical-dependent DNA lesions, resulting in impaired synthesis of critical
      target proteins. DNA lesions were detected 10 days after ADR treatment (3X3 mg/kg
      i.v.) and were still present at the time of onset of the delayed cardiomyopathy.
      PBN, administered by a slow-release osmotic pump to maintain constant plasma
      levels throughout the time of persistence of ADR in the myocardium (approximately
      2 weeks), prevented the development of DNA lesions, as well as the late
      contractile and electrical impairment induced by the anthracycline, thus
      supporting the hypothesis that free radicals play a causal role in both
      phenomena.

PMID- 7733634
TI  - The cytotoxic activity of 1-acyl- and 1,2-diacyl-4,4-diethyl-3,5
      pyrazolidinediones.
AB  - The 1-acyl- and 1,2-diacyl-4,4-diethyl-3,5-pyrazolinediones proved to be
      cytotoxic against the growth of a number of cell lines, including murine and
      human leukemias. HeLa suspended carcinoma, colon adencarcinoma SW480, KB
      nasopharynx and glioma tumors. Selected compounds were also active in the human
      lung bronchogenic MB-9812, and osteosarcoma TE418 screens. These derivatives were
      active in vivo in the Ehrlich ascites carcinoma screen in CF-1 mice at 8
      mg/kg/day I.P. The mode of action in Tmol3 leukemia cells showed that the
      compounds reduced de novo synthesis of purines and pyrimidines and inhibited
      dihydrofolate reductase and ribonucleoside reductase activities. The DNA molecule
      was not a target although limited DNA strand scission may be possible.

PMID- 7733635
TI  - Selectivity of the plasminogen activator inhibitor (PAI-1) for the iso enzyme of
      guanidinobenzoatase on the surface of colonic carcinoma cells.
AB  - The interaction of plasminogen activator-inhibitor (PAI-1) with a cell surface
      protease, guanidinobenzoatase (GB), has been studied in free solution and on the
      surface of colonic epithelial cells. It has been demonstrated that PAI-1
      recognises and inhibits the iso enzymic form of GB associated with colonic
      carcinoma cells but fails to bind to the iso enzymic form of GB associated with
      normal donor colonic epithelial cells. This interaction is mediated by a lysyl
      binding site on the GB: complex formation prevents GB binding to fibrin fibrils
      which also involves lysyl binding sites.

PMID- 7733636
TI  - The cytotoxicity of melphalan and its relationship to pH, hypoxia and drug
      uptake.
AB  - In the present in vitro studies we examined the effect of hypoxia and acidic pH,
      two important consequences of reduced blood flow in vivo, on the cytotoxicity of
      melphalan treatment in Chinese hamster V79-WNRE and SiHa human tumor cells. Cells
      were exposed to various concentrations of melphalan for 1 hr at 37 degrees C
      under oxic or hypoxic conditions; pH 6.6 or 7.4, and cell survival was measured.
      The cytotoxicity of melphalan was potentiated by both low pH and hypoxia, in both
      cell lines. The overall potentiation, expressed as an enhancement ratio (ER),
      from both hypoxia and low pH was 3.5 in V79-WNRE and 2.9 in SiHa cells. The
      potentiation of cell killing produced by hypoxia alone (ERHyp) ranged from 1.4 to
      1.9, and was greater in V79-WNRE than in SiHa cells. The potentiation from low pH
      (ERpH) was approximately 2 in both cell lines. HPLC analysis showed substantial
      intracellular accumulation of melphalan in both cell lines. Hypoxia and reduced
      pH further enhanced uptake of melphalan but this was not sufficient by itself to
      account for the increased potentiation of cytotoxicity observed under those
      conditions.

PMID- 7733637
TI  - A dielectric relaxation study on the effects of the antitumor drugs Lonidamine
      and Rhein on the membrane electrical properties of Ehrlich ascites tumor cells.
AB  - The effects of the anti-tumor drugs lonidamine and rhein on the plasma membrane
      electrical properties of Ehrlich ascites tumor cells were investigated and
      compared. Dielectric relaxation measurements in the radiowave frequency range
      (10(4) to 10(8) Hz) as well as at higher frequencies (10(4) to 10(9) Hz) were
      performed and the data elaborated using a "single-shell" fitting procedure. The
      results obtained in both frequency ranges indicate that membrane conductivity and
      membrane permittivity are altered by 200 microM Lonidamine while 150 microM rhein
      induces only very slight variations in these two plasma membrane parameters. The
      usefulness of the dielectric relaxation technique described here in evaluating
      antitumor drugs and improving clinical protocols is discussed.

PMID- 7733638
TI  - Reduction of cisplatin cytotoxicity on human lung cancer cell lines with N-myc
      amplification by pretreatment with N-myc antisense oligodeoxynucleotides.
AB  - Effect of N-myc antisense oligodeoxynucleotide (ODN) on the proliferation of
      tumor cells and its combined antitumor effect with cisplatin were examined in
      vitro on human lung cancer cell lines with N-myc amplification. The N-myc
      oligomer containing the sequence complementary to the ATG initiation codon
      exhibited a stronger antiproliferative effect on tumor cells than did the
      oligomer not containing the sequence. A significant difference in the anti
      proliferative effect between antisense ODN and sense ODN treatment was observed
      only on tumor cells with N-myc amplification. Pretreatment with antisense ODN
      showed a tendency to reduce rather than enhance cisplatin cytotoxicity.
      Posttreatment with antisense ODN also showed no beneficial effects on cisplatin
      cytotoxicity. This study suggests that pretreatment with antisense ODN may not be
      beneficial when combined with chemotherapy.

PMID- 7733639
TI  - Perturbation of methotrexate transport by verapamil, vinblastine, taurocholate
      and bromosulfophthalein in rat hepatocytes.
AB  - BACKGROUND: Methotrexate (MTX) is extensively used in different combination
      chemotherapy regimens. More knowledge about interactions and their mechanisms in
      target cancer cells and normal cells is needed to improve therapeutic efficacy
      and reduce toxicity. MATERIALS AND METHODS: The effect of verapamil (VRP),
      vinblastine (VBL), taurocholate (TAURO) and bromosulfophthalein (BSP) on MTX
      transport were studied in freshly isolated rat hepatocytes. RESULTS: During 60
      min, 50 microM VRP decreased the hepatocellular MTX accumulation with 29%;
      whereas 100 microM BSP reduced MTX entrance with 15%. 100 microM VBL and 100
      microM TAURO reduced the intracellular accumulation of MTX with 36% and 23%,
      respectively. VRP and BSP appeared to be selective MTX influx blockers, whereas
      VBL and TAURO inhibited both MTX influx and efflux, however, with major
      inhibition on MTX influx. Dixon plot analyses for TAURO and BSP were suggestive
      of competitive inhibition, giving inhibition constants (Ki) values of 105 microM
      for TAURO, and 800 microM for BSP. CONCLUSION: The data demonstrate for the first
      time a selective inhibitory effect of VRP upon MTX influx in isolated rat
      hepatocytes, whereas BSP, a potent MTX efflux inhibitor in malignant cells fails
      to achieve this effect in the normal cell type here investigated.

PMID- 7733640
TI  - In vitro antitumor activity of a new platinum complex, cis-malonato [(4R,5R)-4,5
      bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum (II) (SKI 2053R), against
      human lung and stomach cancer cell lines.
AB  - The in vitro antitumor activity of a new platinum complex, cis-malonato[(4R,5R)
      4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e] platinum(II) (SKI 2053R, NSC
      D644591), cisplatin (CDDP) and carboplatin (CBDCA) was determined against two
      human lung cancer (PC-9 and PC-14) and two human stomach cancer (MKN-45 and KATO
      III) cell lines by human tumor clonogenic assay. The activity of SKI 2053R was
      compared with those of CDDP and CBDCA in terms of relative antitumor activity
      (RAA, peak plasma concentration/IC50). Mean IC50 values (microgram/ml) of SKI
      2053R, CDDP and CBDCA were 6.4 +/- 0.8, 1.8 +/- 0.7 and 20.6 +/- 12.2,
      respectively. The RAAs of SKI 2053R, CDDP and CBDCA were 1.6 +/- 0.4, 2.0 +/- 0.8
      and 1.2 +/- 0.6, respectively. The differences in these values were not
      statistically significant. The results, demonstrating that antitumor activity of
      SKI 2053R is similar to those of CDDP and CBDCA, suggest that SKI 2053R is an
      interesting candidate for further development as a new anticancer drug.

PMID- 7733641
TI  - Expression of genes MAGE-1, -2, and -3 by human maxillary carcinoma cells.
AB  - We analysed the expression of melanoma antigen-encoding (MAGE) gene-1, -2, and -3
      in 20 maxillary carcinomas consisting of two cell lines: freshly isolated cancer
      cells from specimens from 13 patients, and 5 biopsy specimens. The cells were
      subjected to reverse transcription by the polymerase chain reaction. Fourteen
      (70%) out of 20 maxillary carcinomas expressed at least one of the MAGE genes. In
      contrast, five control samples of inflammed mucosa from the maxillary sinus of
      patients with chronic sinusitis were all negative for the expression of these
      genes. Results indicated that patients with maxillary carcinoma may be good
      candidates for specific immunotherapy.

PMID- 7733642
TI  - Effects of danazol on proliferation and viability of 7,12
      dimethylbenz(a)anthracene-induced mammary tumours in rats.
AB  - The suppressive effects of danazol, an isoxazol derivative of a synthetic steroid
      17 alpha-ethinyltestosterone, on cellular viability and DNA synthesis in 7,12
      dimethylbenz(a)anthracene induced mammary tumours were investigated in adult
      female rats by enzyme assays and immunohistochemistry with bromodeoxyuridine
      (BrdU). Rats treated with danazol for 30 days showed a decrease of plasma levels
      of luteinizing hormone and estradiol associated with a dysfunction in hypothalamo
      hypophysial-gonadal axis, resulting in lower activities in succinate
      dehydrogenase and thymidine kinase, and a reduction of BrdU-immunoreactive cells
      in mammary tumours compared with the control, i.e., decreases of viability and
      pyrimidine nucleotide synthesis in tumour cells in danazol-treated rats.

PMID- 7733643
TI  - Direct antitumor effect of cepharanthin and combined effect with adriamycin
      against Ehrlich ascites tumor in mice.
AB  - Direct antitumor effect of cepharanthin (CEP) and the combined effect with
      adriamycin (ADR), as well as the effect of CEP against body weight loss caused by
      treatment of ADR were evaluated using ICR mice bearing Ehrlich ascites tumor.
      Single administration of CEP reduced tumor growth compared to that of the
      untreated control, but not significantly. However, multiple administration of CEP
      reduced the tumor growth significantly compared to that of the untreated control
      (p < 0.001). Simultaneous administration of intratumoral CEP and intravenous ADR
      reduced the tumor growth significantly compared to that of ADR alone (p < 0.05).
      Further, CEP restored body weight loss caused by the treatment of ADR (p < 0.01).
      These findings indicate that the combined administration of CEP and ADR may be
      effective in cancer treatment.

PMID- 7733644
TI  - Influence of the extracellular pH, an inhibitor of Na+/H+ exchanger and an
      inhibitor of Cl-/HCO3-exchanger on adriamycin accumulation.
AB  - We examined the influence of the extracellular pH, an inhibitor of Na+/H+
      exchanger: 3,5-diamino-6-chloro-N-(diaminomethylene) pyrazinecarboxamide
      (amiloride), and an inhibitor of Cl-/HCO3-: 4,4 -diisothiocyanatostilbene -2,2 
      disulfonic acid (DIDS) on the accumulation of adriamycin (ADR) in Ehrlich ascites
      tumor cells and their adriamycin-resistant strain. A good correlation between the
      increases in ADR accumulation and the extracellular pH was shown in the both
      strains. The ADR accumulation decreased with an increasing concentration of
      amiloride or DIDS in both strains. These findings demonstrate that the influx of
      ADR was related closely to the efflux of H+ or to the activities of Na+/H+ ex
      changer and Cl-/HCO3-exchanger. Therefore, raising the extracellular pH and
      enhancement of the activities of either Na+/H+ exchanger or Cl-/HCO3-exchanger
      may result in the potentiation of the cytotoxic effect of ADR through increase of
      ADR influx.

PMID- 7733645
TI  - Mediation by an androgen receptor of the stimulatory effect of testosterone on
      the growth of a fibrosarcoma in the rat.
AB  - We studied the effect of testosterone on the growth of a 20- methylcholanthrene
      induced transplanted fibrosarcoma and assayed androgen receptors in this tumor.
      The effect of an antiandrogen in male rats and the comparative tumor growth in
      females confirmed the androgen sensitivity. A synthetic androgen that strongly
      binds to the androgen receptor was used to characterize the binding activity in
      nuclear extracts of tumor. Scatchard analysis showed that the dissociation
      constant of the hormone receptor complexes (Kd) was 26 +/- 2 nmol/l and the
      number of binding sites was about 95 +/- 12 fmol/mg of protein. The hormone
      receptor complexes sedimented in the region of 3.7 S.

PMID- 7733646
TI  - Combined effects of hyperthermia and CPT-11 on DNA strand breaks in mouse mammary
      carcinoma FM3A cells.
AB  - The interaction between hyperthermia and a DNA topoisomerase I inhibitor, 7-ethyl
      10-(4-(1-piperidyl)-1-piperidyl)-carbonyloxy- camptothecin (CPT-11), was studied
      in the mouse mammary carcinoma FM3A cells. When the cells were treated with CPT
      11 at a concentration of 5 micrograms/ml and 44 degrees C hyperthermia for 60
      min, an enhancement of formation of single stand breaks (ssb) of DNA was
      observed. However, a decrease of ssb was observed when hyperthermia was combined
      with CPT-11 at 50 micrograms/ml. For inhibition of DNA synthesis additive effects
      were observed for treatment with CPT-11 at 5 micrograms/ml combined with
      hyperthermia. On the other hand, protective effects were observed for the
      combined treatment at 50 micrograms/ml. These results indicate that the
      hyperthermic modification of the effect of CPT-11 on the induction of DNA damage
      was diverse at low or high concentrations.

PMID- 7733647
TI  - Low doses of anticancer drugs increase susceptibility of tumor cells to lysis by
      autologous killer cells.
AB  - Pretreatment of squamous cell carcinoma (SCC) cells from four patients with low
      doses of cisplatin, carboplatin or 5-fluorouracil increased the susceptibility to
      lysis by autologous killer cells in vitro. Exposure of two SCC cell lines to low
      doses of these drugs increased the cell surface expression of both HLA class I
      and intercellular adhesion molecule-1 (ICAM-1). HLA class II, neural cell
      adhesion molecule and B7 were not expressed on the cell surface before or after
      such treatment. The results suggest that these drugs increase the susceptibility
      of tumor cells to autologous cell-mediated cytotoxicity, at least in part, by
      enhancing the expression of HLA class I and ICAM-1.

PMID- 7733648
TI  - Modulation of the response to chemotherapy in a human melanoma clone by the site
      of growth in the nude mouse.
AB  - Organ environment has been shown to modulate the efficacy of chemotherapy. A nude
      mouse model was used to study the influence of the in vivo environment on the
      sensitivity to chemotherapy of a human melanoma. A melanoma clone, SB1A, was
      implanted in two different sites (adrenals and subcutis) of nude mice which were
      subsequently treated with high-dose cyclophosphamide. After treatment, a 42%
      complete response rate was observed for the adrenal implants. No response was
      seen in the subcutis despite the same chemotherapy administration. This result is
      not attributable to differences in drug concentration in the target sites,
      because of the high-dose chemotherapy used. This model shows that the in vivo
      environment modifies the sensitivity to chemotherapy of a malignant melanoma
      clone. Further research is needed to clarify the role of host factors and of
      specific cell-stroma interactions that modify the biological behavior of
      malignant cells.

PMID- 7733649
TI  - Enhancement of radiation response of prostatic carcinoma by taxol: therapeutic
      potential for late-stage malignancy.
AB  - Radiation therapy for advanced prostate cancer has dose-limiting complications
      and often results in limited tumor control. A combination of radiation and taxol,
      a potential radiation sensitizer, may enhance therapeutic efficacy at currently
      used individual doses. Human prostatic carcinoma lines in vitro, and Dunning rat
      prostatic adenocarcinoma in vivo, were treated with taxol and radiation
      individually, and in combination. Cytotoxicity of taxol was comparable between
      androgen sensitive and insensitive lines, with 50% growth inhibition at 9.6 to
      12.7 nM. Combining agents increased cytotoxicity, with a dose modifying ratio of
      1.8 at 0.1% survival. Flow cytometry showed an enhancement of radiation toxicity
      associated with taxol-induced cell cycle phase arrest at G2/M. Injection of taxol
      (4 mg/kg/day x 5), radiation dose fractionation (1.5 Gy/day x 5) and their
      combination significantly delayed Dunning tumor growth. Adverse side effects were
      minimal. The results imply that combination of these agents may have clinical
      potential in prostate cancer treatment.

PMID- 7733650
TI  - Evaluation of pre-irradiation on monoclonal antibody localization in colon tumor
      xenografts expressing a cell-associated antigen.
AB  - We have previously demonstrated that external beam irradiation can increase
      radiolabeled monoclonal antibody (MAb) targeting of tumors expressing
      carcinoembryonic antigen (CEA), a secreted glycoprotein. Increased tumor uptake
      was seen with both protons and gamma radiation (60Co). However, although pre
      irradiation with protons resulted in greater activity within tumors than
      conventional radiation, normal tissues also exhibited increased uptake. This
      suggested that proton beam irradiation allowed more CEA to escape and bind to
      radiolabeled MAb in sites other than tumor. The purpose of the present study was
      to determine if a similar effect could be achieved, but without an increase in
      normal tissue activity, with a MAb directed against a cell-bound antigen. T380
      and LS174T human colon tumors were implanted s.c. into athymic nude mice and
      irradiated with 10 Gy 60Co or proton beam. 111In-CYT-103 MAb (anti-TAG-72) was
      injected i.p. 2 hr later and the biodistribution of activity was determined 2
      days thereafter. Tumor size at the time of external beam irradiation and
      biodistribution studies was similar among the groups within each tumor type.
      Increased targeting of radiolabeled MAb within tumors was not observed in either
      model after external beam irradiation compared to their respective nonirradiated
      controls, although some differences were observed in normal tissue uptake. These
      findings demonstrate that preirradiation for the purpose of enhancing MAb
      delivery to the tumor site is not a universal phenomenon and may be successful
      only with certain antibody/tumor antigen systems.

PMID- 7733651
TI  - Families and clans of serine peptidases.
AB  - It has become clear that the proteolytic enzymes that depend upon a serine
      residue for their catalytic activity belong to many different families of
      proteins. We have attempted to group these families in "clans." A clan is defined
      as a group of families the members of which have a common ancestor. That is to
      say, they are homologous, although some of the similarities are in the "twilight
      zone" and the relationships cannot be proven by rigorous statistical methods. We
      believe we can recognize five, or perhaps six, clans of serine peptidases. In
      view of the separate evolutionary origins of the serine peptidases in different
      clans, it is not surprising to find that they may differ greatly and that indeed
      there are few generalizations that can be applied to all serine peptidases. In
      contrast, the members of a clan commonly have marked similarities.

PMID- 7733652
TI  - Interaction of Cu,Zn superoxide dismutase with hydrogen sulfide.
AB  - Addition of HS- enhanced the O(2-)-scavenging activity of bovine erythrocyte
      Cu,Zn superoxide dismutase (EC 1.15.1.1) by about twofold. The positive effect
      was measured using a diverse selection of SOD activity assays, and cannot be an
      artifact restricted to any single technique. Km values for HS- varied in
      different assay techniques, but we estimate Km approximately 80 microM HS-. In
      contrast to HS-, other small molecules tested with SOD either had little effect
      or were inhibitory. Consumption of HS- and O2- occurred in nearly 1:1 mole ratio.
      The products were H2O2 and sulfane sulfur, such as either elemental sulfur or
      polysulfide. Binding of HS- to the enzyme was rapid, with k > 10(7) M-1 s-1. The
      resulting complex exhibited a Cu-to-S charge-transfer absorbance band at 345 nm
      and an altered Cu(II) EPR spectrum. Taken together, these observations suggest
      that HS- binds at the catalytic Cu center of SOD and can be a genuine substrate
      of the enzyme.

PMID- 7733653
TI  - Denaturing behavior of glutathione reductase from cyanobacterium Spirulina maxima
      in guanidine hydrochloride.
AB  - The influence of guanidine hydrochloride (Gdn-HCl) on glutathione reductase from
      Spirulina maxima has been studied by measuring the changes in enzymatic activity,
      protein fluorescence, circular dichroism, thiol groups accessibility, and gel
      filtration chromatography. It was found that the denaturation process involves
      several intermediate states. At low, Gdn-HCl concentrations (Cm = 0.4 M),
      reductase activity was fully lost. However, below 3 M Gdn-HCl, this inhibition
      was freely reversible upon removal of the denaturing agent. Gel filtration
      experiments revealed that this reversible inhibition was not due to dissociation
      of the tetrameric enzyme. Structural studies strongly suggest that the
      conformation of this intermediate state is similar to that of native enzyme. A
      model in which a local region of the polypeptide chain assumes an extended
      conformation (D. T. Haynie, and E. Freire, Proteins 16,115-140) is proposed for
      the reversibly inactivated enzyme. Between 3 and 4 M Gdn-HCl (Cm = 3.5), the
      enzyme activity was irreversibly lost, this inhibition being concomitant with the
      loss of ellipticity, changes in both wavelength and intensity at the maximum of
      fluorescence emission, and dissociation of the enzyme into unfolded monomers;
      these results reveal that gross changes in the protein conformation occur under
      these conditions. At 4 M Gdn-HCl an equilibrium exists between the denatured
      forms of dimer and monomer, which is completely shifted toward the unfolded
      monomers at 5 M Gdn-HCl. Irreversibility in the Gdn-HCl-induced denaturation of
      S. maxima glutathione reductase was not due to aggregation of the unfolded
      enzyme.

PMID- 7733654
TI  - Glycogen concentration and regulation of synthase activity in rat liver in vivo.
AB  - The proportion of liver glycogen synthase in the active (R+I) forms is lower in
      the fed than in the fasted state. This has been attributed to inhibition of
      synthase phosphatase by the accumulated hepatic glycogen. We observed that after
      oral administration of glucose or galactose to fasted rats, hepatic synthase R+I
      activity first increased, as expected, but then decreased to a nadir
      significantly below the control level regardless of the maximal glycogen
      concentration reached. Therefore, we investigated further the relationship of
      hepatic synthase R+I activity and glycogen concentration in vivo in fasted rats
      given increasing oral glucose loads. Male rats fasted 24 h were given glucose
      doses of 0.1-4.0 g/kg by oral gavage (n > or = 8). Liver synthase R+I, total
      synthase, phosphorylase a, glucose, glycogen, glucose-6-P, and UDP glucose were
      measured at intervals over 20-240 min after gavage. Even the smallest glucose
      load elicited rapid glycogen synthesis. The maximum glycogen concentration
      increased linearly with the size of the glucose load, although the proportion of
      administered glucose accounted for by liver glycogen decreased as the glucose
      load increased. The proportion of synthase in the active (R+I) forms peaked at 20
      min after all doses and then declined. By the time the glycogen concentration was
      maximal, synthase R+I activity had decreased to the control value, regardless of
      the glucose dose administered or the maximum glycogen concentration reached.
      Although the decrease in synthase R+I at the time of the glycogen peak was
      correlated with the increase in glycogen concentration, synthase R+I continued to
      decrease for another 1-2 h even though liver glycogen was stable or decreasing.
      The nadir reached was independent of the maximal glycogen concentration. The
      synthase R+I nadir also did not correlate with hepatic glucose or glucose-6-P
      concentrations or phosphorylase a activity. Overall, there was not a
      straightforward temporal or quantitative relationship between the glycogen
      concentration and synthase R+I activity. These data suggest a more complex
      mechanism than simply direct inhibition of synthase phosphatase by glycogen.

PMID- 7733655
TI  - NO+, NO, and NO- donation by S-nitrosothiols: implications for regulation of
      physiological functions by S-nitrosylation and acceleration of disulfide
      formation.
AB  - The biological effects of S-nitrosothiols have been attributed to homolytic
      cleavage of the S-N bond with release of nitric oxide (NO.). Rates of NO. release
      from several S-nitrosothiols were determined by monitoring the oxidation of
      oxymyoglobin to metmyoglobin at pH 7.4; half-lives for oxymyoglobin oxidation
      ranged from seconds to hours. Transnitrosation reactions between S-nitrosothiols
      and thiol-containing amino acids, peptides, and proteins, which indicate the
      ability of nitrosothiols to act as nitrosyl (NO+) donors, occurred more rapidly
      than spontaneous NO. release. Decomposition of S-nitrosodithiols were examined as
      models for the reaction of nitrogen oxides with vicinal thiols on proteins. Rapid
      disulfide formation was accompanied by formation of hydroxylamine and nitrous
      oxide, indicative of nitroxyl (NO-) release. Taken together, these model studies
      demonstrate the ability of S-nitrosothiols to act as NO+, NO., and NO- donors
      under physiological conditions. Transnitrosation and acceleration of disulfide
      formation suggest mechanisms of regulation of protein function through the
      intermediacy of nitrosothiols, and support the notion that biological activities
      of S-nitrosothiols may be associated with heterolytic as well as homolytic
      mechanisms of decomposition.

PMID- 7733656
TI  - Effect of insulin on high-glucose medium-induced changes in rat glomerular
      epithelial cell metabolism of glycoconjugates.
AB  - We have previously reported that incubation of rat glomerular epithelial cells in
      vitro for 8 days with 30 mM glucose without insulin results in reduction in the
      synthesis of a cell layer heparan sulfate proteoglycan (HSPG) species that has
      hydrodynamic size and antigenic characteristics of glomerular basement membrane
      HSPG (1994, Arch. Biochem. Biophys 309, 149-159). In these studies, reduction in
      HSPG synthesis could be attributed either to high-glucose medium or to insulin
      deficiency. In this study we investigated the effects of insulin replacement on
      changes in glomerular epithelial cell metabolism of glycoconjugates induced by
      high-glucose medium. Addition of pharmacologic concentrations of insulin
      prevented the following changes induced by 30 mM glucose: (a) increment in 35SO4
      incorporation into macromolecules in cell layer and medium, (b) increment in the
      synthesis of low anionic macromolecules, probably glycoproteins, in both cell
      layer and medium, (c) increment in synthesis of small-sized glycosaminoglycans
      (Kav 0.75 on Sephrose CL-4B) associated with the cell layer. Insulin was unable
      to correct the 30 mM glucose-induced reduction in the synthesis of cell layer
      HSPG that resembles glomerular basement membrane HSPG. Physiologic concentrations
      of insulin did not affect any of the changes in glycopeptide metabolism induced
      by 30 mM glucose. These findings suggest that (a) inhibition of glomerular
      epithelial cell synthesis of 35SO4-labeled low anionic macromolecules, probably
      glycoproteins, may be involved in insulin-induced reversal of glomerular
      hypertrophy seen in early diabetes, and (b) mechanisms other than insulin lack
      are involved in reduction in the synthesis of glomerular basement membrane HSPG
      in diabetic nephropathy.

PMID- 7733657
TI  - Aspartate aminotransferase isozymes in Panicum miliaceum L., an NAD-malic enzyme
      type C4 plant: comparison of enzymatic properties primary structures, and
      expression patterns.
AB  - Panicum miliaceum has at least three isozymes of aspartate aminotransferase
      (AspAT); the cytosolic and mitochondrial isozymes (cAspAT and mAspAT) are major
      components and the third is a minor isozyme. Fractionation of leaf subcellular
      components showed that the minor isozyme was localized in plastids (pAspAT). We
      purified the three isozymes from green leaves of P. miliaceum. Both cAspAT and
      pAspAT consisted of triple subforms having the same molecular size but different
      isoelectric points. No substantial difference in enzymatic properties was
      observed among these isozymes besides the pH profiles. We isolated a full-length
      cDNA clone for pAspAT. This clone contains an open reading frame that encodes 457
      amino acids. The amino-terminal region of the pAspAT precursor shares common
      features of plastid transit peptides. The amino acid sequence of P. miliaceum
      pAspAT shows higher similarity with other plant pAspATs than P. miliaceum cAspAT
      and mAspAT. The mRNA levels of the three isozymes were high in leaves compared
      with roots and mesocotyls. The three isozymes showed different expression
      patterns against environmental stimuli such as light and nitrate. The activities
      and protein levels of cAspAT and mAspAT increased during greening in accordance
      with those of phosphoenolpyruvate carboxylase and NAD-malic enzyme involved in
      the C4 pathway, primarily as a consequence of the increase in the levels of their
      mRNAs. By contrast, pAspAT was constitutively expressed during greening. The
      activity and protein levels of cAspAT and mAspAT selectively increased during
      recovery from an nitrogen deficit, primarily as a consequence of increase in the
      levels of their mRNAs while those of pAspAT remained unchanged.

PMID- 7733658
TI  - Site-directed mutation in conserved anionic regions of guinea pig liver
      transglutaminase.
AB  - Transglutaminases (EC 2.3.2.13) catalyze the formation of epsilon-(gamma
      glutamyl) lysine cross-links and the substitution of primary amines for the gamma
      carboxamide groups of protein-bound glutamine residues. There are conserved
      anionic regions in transglutaminases, some of which are thought to be possible
      calcium-binding sites. By site-directed mutagenesis, three mutant forms of
      recombinant guinea-pig liver transglutaminase, in which some acidic amino acid
      residues in two conserved regions became nonionic, were expressed in Escherichia
      coli: TGM1, with Asp-231 and -232 changed to Asn; TGM2, with Glu-445, -448, -449,
      -450, and -452 changed to Gln; and TGM3, with the mutations of both TGM1 and
      TGM2. The size and level of synthesis of the mutant proteins were unchanged when
      monitored by immunoblotting. All mutants retained enzyme activity, and their
      apparent Km values for substrates during histamine incorporation into acetyl
      alpha s1-casein were similar to those of the wild-type enzyme, but their Vmax
      values were smaller. The deamidation rate of glutamine residues in the acetyl
      alpha s1-casein was unaffected, but the rate of protein cross-linking catalyzed
      by these mutants was very low. All mutations caused with the enzyme a decrease in
      the sensitivity to activation by calcium and an increase in the sensitivity to
      inhibition by GTP. These results indicated that the negative charges of some
      acidic amino acid residues in the two conserved anionic regions of
      transglutaminase are not essential for its activity but the loss of their
      negative charges affects some catalytic properties.

PMID- 7733659
TI  - The effects of cytochrome b5, NADPH-P450 reductase, and lipid on the rate of 6
      beta-hydroxylation of testosterone as catalyzed by a human P450 3A4 fusion
      protein.
AB  - The recombinant fusion protein containing the heme domain of human P450 3A4 and
      the flavin domains of rat NADPH-cytochrome P450 (P450) reductase
      (rF450[mHum3A4/mRatOR]L1) requires both phospholipid and detergent as well as
      cytochrome b5 (b5) for the NADPH-dependent catalysis of the 6 beta-hydroxylation
      of testosterone. NADPH oxidation results in the formation of hydrogen peroxide in
      the presence or absence of phospholipid and detergent. NADPH oxidation and
      hydrogen peroxide formation are inhibited by the addition of b5 and stimulated
      greater than 3-fold by the addition of testosterone. Marked differences in the
      ability of various phospholipids to support the P450-dependent 6 beta
      hydroxylation of testosterone by the fusion protein were seen. Addition of a 4
      fold excess of purified NADPH-P450 reductase, in the presence of phospholipid,
      detergent, and b5, stimulates the rate of testosterone 6 beta-hydroxylation
      approximately 10-fold, providing turnover rates as high as 80 min-1 for P450 3A4.
      Approximately 30% of the rate of hydrogen peroxide formation is not sensitive to
      inhibition by the P450 inhibitor ketoconazole, suggesting hydrogen peroxide (or
      superoxide anion) formation directly from the reduced flavin domains of the
      fusion protein. It is proposed that the stimulation of NADPH oxidation observed
      following the addition of testosterone to the fusion protein may serve as a
      useful means of monitoring the interaction of other substrates with this P450 and
      thereby permit the rapid screening of chemicals to evaluate their potential
      metabolism by a human P450.

PMID- 7733660
TI  - Molecular cloning and expression of biotin sulfoxide reductase from Rhodobacter
      sphaeroides forma sp. denitrificans.
AB  - Biotin sulfoxide reductase catalyzes the conversion of d-biotin d-sulfoxide (BSO)
      to d-biotin. Oligonucleotides directed against common sequences in Escherichia
      coli biotin sulfoxide reductase and in Rhodobacter sphaeroides f.sp.
      denitrificans dimethyl sulfoxide reductase have been utilized to amplify by PCR a
      651-bp fragment from R. sphaeroides total genomic DNA that showed a high degree
      of sequence similarity with both E. coli biotin sulfoxide reductase and R.
      sphaeroides dimethyl sulfoxide reductase. Screening of a genomic cosmid library,
      prepared from R. sphaeroides genomic DNA, with this probe resulted in the
      isolation of a 7-kb EcoRI-EcoRI fragment that contained the complete coding
      region for R. sphaeroides BSO reductase which has been sequenced. The sequence
      data indicated a single open reading frame of 2231 nucleotides encoding a protein
      of 744 amino acid residues corresponding to a subunit molecular weight of 80,234
      Da. The translated protein sequence contained the prokaryotic Mo-pterin
      signatures 2 and 3 (Mo-cofactor binding motifs) and a ATP/GTP-binding P-loop. The
      R. sphaeroides BSO reductase sequence showed 51% sequence similarity with the
      corresponding E. coli enzyme. In addition, there were only two conserved
      cysteines between the two BSO reductase sequences. The R. sphaeroides gene was
      demonstrated, by complementation, to rescue a mutant E. coli strain that was
      deficient in BSO reductase when grown on BSO as the sole source of biotin. When
      expressed from the FLAG*Shift 12c expression vector, in the presence of IPTG, the
      BSO reductase gene encoded a protein of approximately 80 kDa, which cross-reacted
      with the anti-FLAG monoclonal antibody and exhibited BSO reductase activity by
      the disk microbiological assay.

PMID- 7733661
TI  - Oxidative cleavage of esters and amides to carbonyl products by cytochrome P450.
AB  - A series of esters and several amides were shown to undergo oxidative cleavage
      with the formation of carbonyl products in the presence of purified isoforms of
      liver microsomal cytochrome P450 (P450) in a reconstituted enzyme system. The
      reaction also requires NADPH and NADPH-cytochrome P450 reductase and is
      stimulated by phosphatidylcholine. Kinetic constants were determined in
      experiments in which the predicted aldehyde product was identified and
      quantitated by gas chromatography. A relationship was seen with P450 2E1 between
      the structures of the esters and the Vmax values, with the rates decreasing in
      the series of methyl formate to methyl valerate, and similarly in the series of
      methyl, ethyl, propyl, butyl, and amyl acetates. Furthermore, a clear correlation
      exists between the Km values of the ethyl esters examined and the log of the
      octanol/water partition coefficients of these substrates. With P450 2E1, the Km
      decreases significantly between one and four carbon atoms in the chain length of
      the acyl component of the ester but is unaffected by a further increase in
      length. However, no correlation was found between the Km value and the chain
      length of the alcohol moiety of the esters. Similarly, with P450 2B4 a large
      decrease in Km occurs between one and five carbons in the acyl component of the
      ethyl esters but is unaffected by a further increase in chain length. The
      observed correlation is presumed to arise from hydrophobic interactions between
      the access channel to the active site of P450 and the acyl side chain of the
      esters. P450 1A2 is also active in ester cleavage, and the three cytochromes
      examined with esters are active in the conversion of N-alkyl amides to aldehydes,
      as are P450s 2C3, 1A1, and 3A6. Studies on 2-butyl acetate oxidation by P450 2B4
      in the presence of 18O2 showed 88% 18O incorporation into the product, 2
      butanone. This is consistent with a mechanism that involves hydroxylation at the
      alpha-carbon of the alcohol component of the ester to yield an unstable geminal
      hydroxy ester, as proposed earlier by F. P. Guengerich et al. (1988, J. Biol.
      Chem. 263, 8176-8183) for several dihydropyridine carboxylic esters. Our results
      further indicate that such an intermediate decomposes by a nonhydrolytic
      mechanism and also rule out the possibility of transient ester hydrolysis with
      subsequent oxidation of the alcohol formed. In addition, they establish that
      oxidative cleavage is a widespread reaction among P450 cytochromes and commonly
      used esters and amides.

PMID- 7733662
TI  - Rates of elementary steps catalyzed by rat liver cytosolic and mitochondrial
      inorganic pyrophosphatases in both directions.
AB  - We have investigated kinetics of pyrophosphate synthesis and phosphate-water
      oxygen exchange catalyzed by rat liver cytosolic and mitochondrial
      pyrophosphatases in the presence of Mg2+ as cofactor. A common kinetic model
      derived for these reactions implies that they involve formation of enzyme-bound
      pyrophosphate and proceed through two parallel pathways: pathway I, utilizing two
      magnesium phosphate molecules, and pathway II, utilizing both magnesium phosphate
      and free phosphate. Pyrophosphate formation is greatly facilitated in the active
      sites of both pyrophosphatases ([E.PPi]/[E.2Pi] = 0.11-0.24) compared to
      solution. The rate constants for PPi binding/release, bound PPi
      hydrolysis/synthesis, and two Pi binding/release steps catalyzed by cytosolic and
      mitochondrial pyrophosphatases were enumerated for pathway I. There is no unique
      rate-limiting step for pathway I for both enzymes in either direction. A
      modulating effect of magnesium phosphate on the oxygen exchange is observed with
      the cytosolic pyrophosphatase, explicable in terms of an allosteric phosphate
      binding site or random-order release of two phosphate molecules from the active
      site. A remarkable feature of these mammalian pyrophosphatases versus their
      microbial counterparts is their high efficiency in pyrophosphate synthesis. The
      turnover numbers in the direction of synthesis are 14 and 9.3 s-1 for the
      cytosolic and mitochondrial enzymes, respectively (9 and 16% relative to
      hydrolysis turnover numbers). The results demonstrate that the enzyme-catalyzed
      synthesis of pyrophosphate, the simplest high-energy polyphosphate, can proceed
      at a high rate in the absence of an external energy input, such as that provided
      by protonmotive force in membrane systems.

PMID- 7733663
TI  - A redox-dependent function of thioredoxin is necessary to sustain a rapid rate of
      DNA synthesis in yeast.
AB  - DNA replication is impaired in mutants of Saccharomyces cerevisiae which lack the
      two thioredoxin genes TRX1 and TRX2. Trx1p supports a normal rate of DNA
      replication only if the active site contains the redox active cysteines. Two
      mutant forms of Trx1p, one containing a Cys30Ser mutation and a second containing
      the Cys30Ser mutation in combination with a Cys33Ser mutation, were unable to
      sustain normal rates of DNA synthesis. The thioredoxin active-site mutants
      completed a round of replication in 66 min as opposed to 18 min observed for an
      isogenic wild type culture. Western blot analysis, using antibody generated
      against purified 6 x His-tagged Trx1p, showed that both mutant forms of Trx1p
      were present at the same levels as the wild-type protein. Thus the inability of
      the mutant proteins to promote DNA synthesis is not caused by degradation or poor
      expression, but rather by the loss of their reductive capacity. The results show
      that an optimal rate of DNA synthesis requires a redox function of thioredoxin.
      Since the measured levels of deoxyribonucleotides are normal in the thioredoxin
      mutants, thioredoxin either participates with ribonucleotide reductase in
      channeling a small subset of deoxyribonucleotides to sites of replication, or
      thioredoxin reduces and thereby activates an unidentified component of the
      replication machinery.

PMID- 7733664
TI  - Enzymatic deimination of glycogen phosphorylase and a peptide of the
      phosphorylation site: identification of modification and roles in phosphorylation
      and activity.
AB  - The functional role of arginine residues in glycogen phosphorylase b was probed
      by enzymatic modification by using peptidylarginine deiminase, which converts
      arginine residues to citrulline. A peptide with sequence
      LysArgLysGlnIleSerValArgGlyLeu, corresponding to the phosphorylation site of
      serine-14 in phosphorylase, was a substrate for the deiminase. Although both
      arginine residues could be converted to citrulline, modification of arginine-16
      occurred more rapidly than modification of arginine-10. Previous studies have
      implicated a role for arginine, notably arginine-16, in determining phosphorylase
      kinase activity with the peptide. Deimination altered the phosphorylation of the
      peptide. Monodeimination of the peptide at arginine-16 slowed down the
      phosphorylation reaction, but did not diminish the total amount of
      phosphorylation that could be obtained. Deimination of both arginines produced a
      peptide that could not be phosphorylated. Modification of phosphorylase b
      resulted in activation or inactivation of enzyme activity depending on the extent
      of reaction with peptidylarginine deiminase. A low level of deiminase causes
      inactivation initially, but after prolonged incubation activation occurs. With
      high level of deiminase only activation can be observed. Because changes in
      activity are seen only at subsaturating AMP concentrations (50-100 microM),
      inactivation and activation are likely due to changes in affinity of the enzyme
      for AMP. The protein modified with the high level of deiminase has multiple sites
      of deimination. Arginine 16 was established as a major site of modification. Only
      protein modified with the high level of deiminase showed modification of arginine
      16 and effects on the phosphorylation of phosphorylation b. As with the modified
      peptide substrate, the reaction was slower with modified phosphorylase in
      comparison with native phosphorylase b. The results show the importance of the
      guanidino group of arginine-16 of the protein substrate in modulating the
      phosphorylase kinase reaction.

PMID- 7733665
TI  - Studies of calcineurin-calmodulin interaction: probing the role of arginine
      residues using peptidylarginine deiminase.
AB  - We have used an enzyme, peptidylarginine deiminase, to convert certain arginyl
      groups in calcineurin to citrulline. Amino acid analysis shows that only 3 of 34
      arginines in calcineurin were deiminated; citrulline seems to be localized only
      in the calcineurin A (CaN A) subunit. Upon incubation with deiminase, the
      Mn2+/calmodulin-stimulated phosphatase activity decreases to 20-40% of the
      original activity within 1 h. However, the reduction in enzyme activity is fully
      protected by addition of calmodulin to the deimination reaction, and only 1.5 mol
      citrulline/mol calcineurin is found in this case. Removal of the calmodulin
      binding domain of the deiminated CaN A by limited proteolysis results in the
      reactivation of the phosphatase to the same level as digested native calcineurin
      and also results in the loss of all citrulline residues. The calmodulin
      activation curve of the deiminated enzyme is significantly shifted; the
      calculated apparent Kact using native calmodulin is 15-fold higher than that of
      native calcineurin while the apparent Kact using a fluorescent derivative of
      calmodulin, dansyl-calmodulin, is 10-fold higher. However, the Vm of deiminated
      calcineurin is similar to that of native if highly elevated levels of calmodulin
      are used to activate the modified calcineurin. To determine directly if the
      binding of calmodulin to calcineurin is affected upon deimination, fluorescence
      titrations using dansyl-calmodulin were performed. The Kd of deiminated
      calcineurin determined from these titrations is 10-fold higher than that of
      unmodified calcineurin, indicating that calmodulin binding is indeed affected.
      These data indicate that at least one arginine is important for calmodulin
      binding and is likely located at the calmodulin binding site of the CaN A
      subunit.

PMID- 7733666
TI  - Prostaglandin H synthase-2 is induced in Syrian hamster embryo cells in response
      to basic fibroblast growth factor.
AB  - Metabolites of arachidonic acid and linoleic acid can serve as regulators of the
      epidermal growth factor signal transduction system in Syrian hamster embryo (SHE)
      fibroblasts. We have now investigated the possible role of these lipids in
      modulating the signal transduction of basic fibroblast growth factor (bFGF), a
      potent mitogen to SHE fibroblasts. The addition of bFGF (0.1 to 1.0 ng/ml) to
      serum-deprived SHE cells stimulated a six- to sevenfold increase in the
      incorporation of thymidine into DNA. Structural analysis indicated that bFGF
      stimulated the metabolism of exogenous and endogenous arachidonic acid to
      primarily PGE2, PGF2 alpha, and PGD2, with lesser amounts of uncharacterized
      prostaglandins observed. The metabolism of linoleic acid in SHE cells was not
      affected by bFGF. bFGF stimulated the expression of the inducible form of
      prostaglandin H synthase (PGHS-2) as determined by Northern analysis using murine
      PGHS-2 cDNA as the probe. PGHS-2 protein in the SHE cells was also increased by
      bFGF as determined by Western analysis using antibodies specific for PGHS-2.
      Levels of the constitutive (PGHS-1) enzyme and mRNA were not altered by bFGF.
      Preincubation of the cells with 1-2 microM dexamethasone significantly inhibited
      bFGF-stimulated expression of PGHS-2 protein and mRNA. Dexamethasone potently
      inhibited bFGF induced mitogenesis in these cells. Pretreatment of SHE cells with
      indomethacin inhibited bFGF-dependent mitogenesis, as well as endogenously
      produced PGE2. The data suggests that regulation of PGHS-2 expression may be an
      element of the bFGF mitogenic signal transduction pathway.

PMID- 7733667
TI  - Molecular cloning and expression of mouse mg(2+)-dependent protein phosphatase
      beta-4 (type 2C beta-4).
AB  - A full-length complementary DNA (cDNA) clone (pTK-3) encoding an isoform of
      Mg(2+)-dependent protein phosphatase beta (MPP beta-4) was isolated for the first
      time from a mouse melanocyte cDNA library. It was strongly suggested that the
      mRNA corresponding to the pTK-3 insert was a splicing variant of a single pre
      mRNA that also encodes MPP beta-1 and -2 (T. Terasawa, T. Kobayashi, T. Murakami,
      M. Ohnishi, S. Kato, O. Tanaka, H. Kondo, H. Yamamoto, T. Takeuchi, and S.
      Tamura, 1993, Arch. Biochem. Biophys. 307, 342-349). The amino acid sequence of
      MPP beta-4 differed from those of MPP beta-1 and -2 only at the carboxyl terminal
      region. Analysis by reverse transcriptase polymerase chain reaction (RT-PCR)
      revealed that MPP beta-4 mRNA was expressed only in testis and intestine and not
      in other mouse tissues tested. Specific expression of the mRNA signals of two
      other isoforms of MPP beta, MPP beta-3 and -5 (a novel isoform), in testis and
      intestine was also demonstrated by the RT-PCR. The carboxyl terminal region of
      MPP beta-5 was found to have a chimera structure composed of part of MPP beta-1
      and part of MPP beta-3. The recombinant MPP beta-3 and -4 and the putative MPP
      beta-5 expressed in Escherichia coli cells exhibited Mg(2+)-dependent and okadaic
      acid-insensitive protein phosphatase activities. It was demonstrated that the
      mRNA expression levels of MPP beta-3, -4, and -5 alter according to the
      maturation of mouse testis. These results suggest that the complex structure of
      MPP beta isoforms and their tissue- and developmental stage-specific expression
      reflect the variety of their physiological functions.

PMID- 7733668
TI  - Cytochrome and alternative respiratory pathways compete for electrons in the
      presence of pyruvate in soybean mitochondria.
AB  - The partitioning of electrons between the alternative oxidase and the cytochrome
      pathway of soybean mitochondria has been reassessed in the presence of the
      alternative oxidase activator pyruvate. In the presence of pyruvate and with
      succinate as substrate, the alternative oxidase became active at a much lower
      level of ubiquinone reduction than in the absence of pyruvate. Under state 4 (no
      ADP present) conditions, activation of the alternative oxidase with pyruvate
      resulted in an oxidation of b cytochromes, demonstrating switching of electrons
      away from the cytochrome chain. In the presence of ferricyanide and the
      cytochrome oxidase inhibitor KCN, cytochrome chain activity could be followed
      spectrophotometrically and that of the alternative pathway with an oxygen
      electrode. Under these conditions, the addition of pyruvate diverted electron
      flow from the cytochrome chain to the alternative pathway; subsequent inhibition
      of the alternative oxidase increased electron flow via the cytochrome chain. This
      indicates that electrons can be switched from one pathway to the other when the
      cytochrome chain is not saturated and this was confirmed by n-propylgallate
      titrations (p plots) of mitochondria oxidizing succinate. Decreases in ADP/O
      ratios and phosphorylation rate upon addition of pyruvate indicated that the
      alternative pathway could also contribute to respiration under state 3
      conditions. The results indicate that when the alternative oxidase is activated
      by pyruvate, it can compete for electrons with the cytochrome chain and does not
      act as an overflow pathway. The significance of these observations for in vivo
      respiration is discussed.

PMID- 7733669
TI  - Metabolism of cottonseed microsomal N-acylphosphatidylethanolamine.
AB  - N-acylphosphatidylethanolamine (NAPE) was recently shown to be synthesized in
      vitro in cottonseed microsomes by the direct N-acylation of
      phosphatidylethanolamine (PE) with unesterfied fatty acids (K.D. Chapman and T.
      S. Moore, 1993, Plant Physiol. 102, 761-769). Here we examine the relationship of
      the synthesis and turnover of NAPE in cottonseed microsomes to the O-acylation of
      other membrane phospholipids. PE was N-acylated in a time-dependent manner with
      [1-14C]palmitic acid independent of exogenously supplied ATP. O-Acylation of PE
      and phosphatidylcholine (PC) with [1-14C]palmitic acid proceeded only in the
      presence of ATP. Further radiolabeling experiments with [1-14C]palmitoylCoA and
      phosphatidyl(N-[1-14C]-palmitoyl)ethanolamine indicated that O-acylation of
      phospholipids occurred via an acylCoA intermediate and not via an NAPE
      intermediate. [1-14C]palmitic acid was released from PC[1-14C-dipalmitoyl] in
      cottonseed microsomes in a Ca(2+)-dependent manner and this [14C]-FFA was
      incorporated into [14C]NAPE in a linear fashion. Cottonseed NAPE was selectively
      hydrolyzed to N-acylethanolamine (NAE) and N-acyl lysophosphatidylethanolamine
      (NAlysoPE) by Ca(2+)-independent, membrane-bound phospholipase D and A
      activities, respectively. NAlysoPE was not hydrolyzed to NAE, indicating that the
      phospholipase D that was active toward NAPE did not recognize NAlysoPE; instead
      NAlysoPE was converted to NAPE in the presence of Ca2+. Collectively, our results
      indicate that NAPE synthesis and the O-acylation of other phospholipids occur by
      two separate pathways and that microsomal NAPE is selectively turned over by
      membrane-bound phospholipase activities. A pathway for the metabolism of
      cottonseed NAPE is outlined.

PMID- 7733670
TI  - Superoxide from glucose oxidase or from nitroblue tetrazolium?
AB  - Glucose oxidase reduces nitroblue tetrazolium, or ferricytochrome c, faster
      anaerobically than aerobically. This result is inconsistent with the conclusion
      that GO2 can reduce O2 to O2- which is then responsible for the reduction of NBT
      and of cytochrome c. Nevertheless, the aerobic reductions are partially
      inhibitable by superoxide dismutase. A scheme of reactions is proposed which
      explains why these electron acceptors cause an O2- production which does not
      occur in their absence when O2 is the sole electron acceptor.

PMID- 7733671
TI  - Aging of the liver: proteolysis of oxidatively modified glutamine synthetase.
AB  - During aging cells accumulate altered forms of proteins, notably oxidatively
      modified proteins. The multicatalytic protease selectively degrades oxidized
      proteins, suggesting that the age-related accumulation of oxidized proteins might
      be a consequence of decreased activity of this protease. The protease activity of
      liver homogenates was assayed with an improved fluorimetric method, using
      oxidatively modified glutamine synthetase as substrate. Application of this assay
      to extracts from liver of Fischer 344 rats from both Japan and the United States
      demonstrated a marked preference for the oxidized substrates, as expected.
      Extracts from animals ages 8 to 26 months maintain both total proteolytic
      activity and the ability to distinguish between native and oxidized substrates.
      Oxidatively modified hepatocyte extracts were also employed as substrate, and
      older animals again maintained proteolytic activity. The multicatalytic protease
      was purified from liver of young and old rats, and the specific activity of the
      preparations were comparable when assayed with oxidatively modified glutamine
      synthetase. We conclude that the intrinsic neutral or alkaline proteolytic
      activity of rat liver is maintained during aging.

PMID- 7733672
TI  - Effect of ascorbate on the DT-diaphorase-mediated redox cycling of 2-methyl-1,4
      naphthoquinone.
AB  - Following the two-electron reduction of 2-methyl-1,4-naphthoquinone by rat liver
      DT-diaphorase (also called NAD(P)H: (quinone acceptor) oxidoreductase, EC
      1.6.99.2), the hydroquinone product is slowly autoxidized to the quinone in
      buffered solutions at pH 7.0. The autoxidation, which generates the superoxide
      radical (O2-.) and other reactive oxygen species, is the rate-limiting step in
      the oxidation-reduction (redox) cycling of the quinone. The addition of ascorbate
      to these reaction mixtures increases the rate of redox cycling. Two mechanisms
      are proposed to explain this increase: (1) ascorbate reduces the quinone in a one
      electron reduction and (2) if Fe(3+)-EDTA is present, ascorbate reduces the metal
      chelate in a one-electron reduction. Both mechanisms produce O2-. which initiates
      the free radical chain reaction that results in autoxidation of the hydroquinone.
      Although ascorbate may be a physiologically important antioxidant under some
      conditions, the studies reported here show that ascorbate is a prooxidant in the
      redox cycling of 2-methyl-1,4-naphthoquinone and, as such, could increase the
      potential toxicity of this quinone.

PMID- 7733673
TI  - Cloning and expression of a cDNA for mu-class glutathione S-transferase from
      rabbit liver.
AB  - A mu-class glutathione S-transferase (GST) cDNA clone, pHMB1, from rabbit liver
      has been constructed, using a 748-base-pair fragment of GST Yb1 cDNA as a probe.
      The nucleotide sequence of pHMB1 has been determined, and the complete amino acid
      sequence has been deduced. Recombinant clone pHMB1 contains a cDNA insert of 1443
      base pairs with 654 nucleotides of open reading frame, 33 nucleotides of 5'
      untranslated region, and 756 nucleotides of 3'-untranslated region. The open
      reading frame encodes a polypeptide (rbGST mu I) comprising 218 amino acids with
      molecular weight of 25,417. Compared to published mu-class GST sequences, rbGST
      mu I is 73 and 77% identical to rat Yb1 and human GST4 in amino acid sequence,
      respectively. The pHMB1 was expressed in Escherichia coli using expression vector
      pIH821 and the expressed GST was purified as a single band on polyacrylamide gel
      electrophoresis by maltose- and glutathione-affinity column chromatography.
      Rabbit liver GST protein expressed by this system was catalytically active. The
      functional characterization was done on the expressed protein. The rabbit liver
      GST expressed in E. coli showed greater activity toward 1,2-dichloro-4
      nitrobenzene than mu-class isozymes in rabbit hepatic tissue (T. Primiano and
      R.F. Novak (1993) Arch. Biochem. Biophys. 301, 404-410). Enzymatic activity of
      expressed protein toward the substrate 1-chloro-2,4-dinitrobenzene was inhibited
      by triethyltin bromide, Cibacron blue, triphenyltin chloride,
      bromosulfophthalein, and hematin. RNA blot hybridization demonstrated that the
      pHMB1 mRNA was well expressed in rabbit liver, brain, and kidney.

PMID- 7733674
TI  - Active recombinant human cytosolic phospholipase A2 is expressed in Escherichia
      coli.
AB  - The cDNA encoding human cytosolic phospholipase A2 (cPLA2) has been subcloned
      into a prokaryotic pET16b expression vector which also encodes an amino-terminal
      deca-histidine affinity tag to facilitate purification of the recombinant enzyme.
      Soluble, active fusion protein, designated His-cPLA2, has been obtained
      reproducibly from this expression system using the E. coli strain BL21 (DE3). The
      protein has been purified to homogeneity in four steps and the mass confirmed by
      electrospray mass spectrometry. His-cPLA2 was characterized by kinetic analysis
      which demonstrated that the enzyme is similar to native cPLA2 in all respects
      investigated. Specifically, the enzyme binds to anionic vesicles containing
      substrate, and acts processively on these vesicles. Enzymatic activity is
      supported by the presence of Ca2+ and several other divalent metal ions, and is
      inhibited by several transition metal ions. Finally, the enzyme demonstrates
      lysophospholipase activity and exhibits a high selectivity for sn-2 arachidonyl
      esters. This prokaryotic expression system yields moderate amounts of unmodified
      recombinant His-cPLA2 and is advantageous for rapid production of protein and
      mutational analyses.

PMID- 7733675
TI  - The in vivo cytoprotection of ascorbic acid against ischemia/reoxygenation injury
      of rat liver.
AB  - The in vivo effects of ascorbic acid on the reoxygenated liver tissue were
      examined, with regard to the following effects: (i) the effects of scavenging
      radicals and/or reducing peroxidative reactions, and (ii) the effects of the
      chelation with low-molecular-weight iron and increasing its reactivity (radical
      production). Ascorbic acid is one of the water-soluble vitamins known to have
      various physiological effects involving both chelating and reducing properties at
      once. Lipid peroxidation of the reoxygenated liver tissue estimated by the
      production of TBARS (thiobarbituric acid-reactive substance) and LPO (lipid
      hydroperoxides) was suppressed effectively by the preischemic intraperitoneal
      administration of ascorbic acid. Ascorbic acid also showed this anti-oxidant
      effect in a dose-dependent manner. The analysis of the levels of ascorbic acid
      and glutathione of the liver tissue revealed that ascorbic acid works as an anti
      oxidant probably by being oxydized finally to dehydroascorbic acid just after the
      reoxygenation. The latter was reduced to ascorbic acid again, coupled with the
      conversion of GSH to GSSG in the postischemic time course. The predominant effect
      of ascorbic acid on the reoxygenated liver tissue seems to be caused by the
      scavenging radicals and/or reducing peroxidative reactions, rather than by
      chelating iron and increasing its reactivity (radical production). Cellular
      integrity (estimated by the release of GOT, GPT, and LDH) and the energy state of
      the postischemic liver tissue (estimated by the tissue ATP level) were also well
      preserved by the administration of ascorbic acid.

PMID- 7733676
TI  - Subcellular localization, aggregation state, and catalytic activity of microsomal
      P450 cytochromes modified in the NH2-terminal region and expressed in Escherichia
      coli.
AB  - This laboratory previously expressed cDNAs encoding rabbit liver cytochrome P450
      2E1 (the ethanol-inducible isoform) and the corresponding protein lacking amino
      acids 3-29, a proposed membrane anchor, in Escherichia coli. Unexpectedly, the
      shortened protein, like the full-length form, was found to be predominantly
      located in the bacterial inner membrane rather than the cytosol and to have full
      catalytic activity. Additional proteins with alterations in the NH2-terminal
      region of P450 2E1 or P450 2B4 (the phenobarbital-inducible isoform) were
      similarly expressed, and it was concluded that such modifications can change the
      cytochrome to an increased cytosolic localization and that the first two
      hydrophobic segments are not uniquely involved in attachment to the bacterial
      membrane (Pernecky et al., 1993, Proc. Natl. Acad. Sci. USA 90, 2651-2655). In
      the present study, three chimeric cytochromes were produced to determine the
      effect on subcellular localization: 2E1:2B4, in which the first 17 residues of
      2E1 (delta 3-29) replaced the corresponding 17 residues in 2B4 (delta 2-27), and
      BM-3:2B4 and BM-3:2E1, in which the first 19 residues of P450BM-3 replaced the
      first 17 in 2B4 (delta 2-27) and 2E1 (delta 3-29), respectively. Of the total
      cytochrome expressed, the localization in the E. coli cytosol was about 60, 70,
      and 80% for the respective chimeras, with 80% being the highest for any P450 we
      have examined. A plot of the extent of membrane binding versus hydropathy of the
      NH2-terminal region showed that the terminal sequence strongly influences the
      subcellular distribution and that a group of 2E1 proteins and a group of 2B4
      proteins each have other regions that characteristically determine the extent of
      membrane attachment. The role of the NH2-terminal region in the high level of
      aggregation of purified full-length P450 is indicated by the finding that the
      multimeric state of 2E1 or 2B4 is unaffected by sodium cholate at concentrations
      that convert 2E1 (delta 3-29) or 2B4 (delta 2-27) to the monomeric state. In
      contrast to our earlier experience with P450 2E1, purified P450 2B4 (delta 2-27)
      has on the average only about half the activity of full-length 2B4 with
      substrates that undergo oxidative dealkylation or oxygenation at a hydroxyl
      group.

PMID- 7733677
TI  - Transient kinetics of intracomplex electron transfer in the human cytochrome b5
      reductase-cytochrome b5 system: NAD+ modulates protein-protein binding and
      electron transfer.
AB  - Transient kinetics of reduction and interprotein electron transfer in the human
      cytochrome b5 reductase-cytochrome b5 (b5R-b5) system was studied by laser flash
      photolysis in the presence of 5-deazariboflavin and EDTA at pH 7.0. Flash-induced
      reduction of the FAD cofactor of b5R by deazariboflavin semiquinone (in the
      absence of b5) occurred in a rapid second-order reaction (k2 = 3.1 x 10(8) M-1 s
      1) and resulted in a neutral (blue) FAD semiquinone. The heme of cytochrome b5
      (in the absence of b5R) was also rapidly reduced in this system with k2 = 3.1 x
      10(8) M-1 s-1. When the two proteins were mixed at low ionic strength, a strong
      complex was formed. Although the heme of complexed b5 could be directly reduced
      by deazariboflavin semiquinone, the second-order rate constant was nearly an
      order of magnitude smaller than that of free b5 (k2 = 3.4 x 10(7) M-1 s-1). In
      contrast, access to the FAD of b5R by the external reductant was decreased by
      considerably more than an order of magnitude (k2 < 1 x 10(7) M-1 s-1). When an
      excess of b5R was titrated with small increments of b5 and then subjected to
      laser flash photolysis in the presence of deazariboflavin/EDTA, interprotein
      electron transfer from the b5R FAD semiquinone to the heme of b5 could be
      observed. At low ionic strength (I = 16 mM), the reaction showed saturation
      behavior with respect to the b5 concentration, with a limiting first-order rate
      constant for interprotein electron transfer k1 = 375 s-1, and a dissociation
      constant for protein-protein transient complex formation of approximately 1
      microM. The observed rate constants for interprotein electron transfer decreased
      23-fold when the ionic strength was increased to 1 M, indicating a plus-minus
      electrostatic interaction between the two proteins. Saturation kinetics were also
      observed at I = 56, 96, and 120 mM, with limiting first-order rate constants of
      195, 155, and 63 s-1, respectively. In the presence of NAD+, the transient
      protein-protein complex was stabilized by approximately a factor of two, and
      limiting first-order rate constants of 360 s-1 were obtained at both I = 56 mM
      and I = 96 mM and 235 s-1 at I = 120 mM. Thus, NAD+ appears to stabilize as well
      as to optimize the protein-protein complex with respect to electron transfer.
      Another effect of NAD+ is to appreciably slow autoxidation and disproportionation
      of the FAD semiquinone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733678
TI  - 1H NMR characterization of a hen ovalbumin tyrosinamide N-linked oligosaccharide
      library.
AB  - A library of 15 N-linked oligosaccharide structures was prepared from ovalbumin
      and characterized using high-field NMR and mass spectrometry. The
      oligosaccharides were enzymatically released from ovalbumin glycopeptides, and
      the reducing ends were reacted with ammonium bicarbonate to form oligosaccharide
      glycosylamines. These reacted with Boc-tyrosine-N-hydroxysuccinimide ester,
      resulting in a mixture of tyrosinamide-oligosaccharides. The Boc group was
      removed to expose an amine terminus which enhanced the resolution of tyrosinamide
      oligosaccharides when chromatographed on reverse-phase HPLC. Ten major and five
      minor oligosaccharides were purified on a micromole scale and characterized using
      1H NMR and FAB-MS. The structures include high-mannose, hybrid, and complex
      oligosaccharides possessing from two to five antenna, providing the most complete
      definition of ovalbumin N-linked oligosaccharides to date. The resulting library
      is well suited to biological studies due to the presence of a single terminal
      tyrosine residue on each oligosaccharide that allows radioiodination or the
      attachment of additional probes to these glycoconjugates prior to biological
      studies.

PMID- 7733679
TI  - Mutagenesis of an amino acid residue in the activator-binding site of
      cyanobacterial ADP-glucose pyrophosphorylase causes alteration in activator
      specificity.
AB  - The specificity for activator of ADP-glucose pyrophosphorylase is closely related
      to the corresponding major carbon-assimilation pathway. The enzyme from
      Escherichia coli is mainly activated by fructose-1,6-P2, while the
      cyanobacterial, algal, and higher-plant enzymes are activated by 3-P-glycerate.
      Previous results have shown that Lys39 of the E. coli enzyme is involved in the
      binding of fructose-1,6-P2 while for the Anabaena enzyme, lysine residues 382 and
      419 have been shown to be involved in the binding of 3-phosphoglycerate. This
      report shows that if Lys419 of the Anabaena enzyme is changed to glutamine,
      activation of the cyanobacterial enzyme by fructose-1,6-P2 becomes more effective
      than that of 3-P-glycerate at lower concentrations. Kinetic studies show that
      fructose-1,6-P2 competitively inhibits 3-P-glycerate activation of the Anabaena
      wild-type enzyme, suggesting that these two compounds bind to the same site. Thus
      a change of one amino acid at the activator binding domain can affect the
      specificity of activation of the Anabaena ADP-glucose pyrophosphorylase.

PMID- 7733680
TI  - Amino acid sequence of a new type of toxic phospholipase A2 from the venom of the
      Australian tiger snake (Notechis scutatus scutatus).
AB  - Venom from the common tiger snake, Notechis scutatus scutatus, contains several
      toxic acidic proteins which promote hypotension and hemorrhage in mice. One of
      these toxins, HTe, has a phospholipase A2 (PLA2) amino acid sequence. It contains
      125 amino acids rather than the 119/120 found in other N. s. scutatus PLA2s,
      because it also has the loop of residues (62-66) found in helix D of pancreatic
      PLA2s, the gamma-subunit of taipoxin, and the D-subunit of textilotoxin. High
      sequence identity is found between the first 57 and the last 25 amino acids of
      HTe and other N. s. scutatus PLA2s. In the central section containing the
      pancreatic loop and the beta-wing, sequence similarity with other N. s. scutatus
      PLA2s is low. The beta-wing amino acids are highly homologous to taipoxin-gamma.
      HTg, an isoform of HTe, has a sequence almost identical to that of HTe in the
      central section. Neuropharmacological and neurophysiological studies show that
      HTe blocks neuromuscular transmission, but it does not produce blockade by virtue
      of a selective action on nerve endings. Instead, the toxin acts both on nerve and
      on muscle. Unlike taipoxin-gamma and textilotoxin-D, HTe and HTg are not
      glycosylated and are not otherwise modified. HTe, HTg, and the other acidic
      proteins hydrolyze the synthetic PLA2 substrate, 3-octanoyloxy-4-nitrobenzoic
      acid, as well as L-alpha-phosphatidylcholine.

PMID- 7733681
TI  - Cloning, functional expression, and pharmacology of a GABA transporter from
      Manduca sexta.
AB  - Termination of synaptic transmission occurs by several mechanisms that include
      uptake of the neurotransmitter molecules into the presynaptic neuron by
      specialized membrane transport proteins. We have cloned a (DABA)-sensitive gamma
      aminobutyric acid (GABA) transporter from a cDNA library from Manduca sexta
      embryo. The cDNA clone, MasGAT, shows high sequence homology to known mammalian
      GABA transporters. The transcript is about 5.5 kb with an open reading frame of
      1793 bp. Injection of a 2.2-kb cRNA from this clone into Xenopus oocytes results
      in [3H]GABA transport. A Michaelis-Menten kinetic analysis shows that GABA
      transport occurs by a high-affinity and saturable process, suggesting that it is
      carrier-mediated. Ion substitution studies also show the transport process to be
      highly dependent on extracellular Na+ gradient, a finding that is consistent with
      properties of known mammalian neurotransmitter transporters. Although MasGAT
      shares certain pharmacological similarities with known mammalian GABA
      transporters, this transporter is pharmacologically distinct from the known
      mammalian GABA transporters.

PMID- 7733682
TI  - [Expression of dominant oncogenes and tumor suppressor genes in bladder
      carcinoma].

PMID- 7733683
TI  - [Environment, patient information, and organization in a pediatrics urodynamics
      unit].
AB  - OBJECTIVES: Urodynamic studies require patient cooperation, and this can be
      difficult in the pediatric age due to their invasive nature. Our aim was to
      assess the benefits of organization, facility design and information specifically
      adapted to children. METHODS: We describe the facility design and organization of
      the Urodynamics Unit at the Children's Hospital in Boston. Environmental factors
      are adapted to the pediatric age and aim to reduce the impact of the examination.
      There are child's objects, images and toys in the examining room. Parents are
      allowed to be in the room while the test is performed, and music is played during
      the procedure. We describe the information pattern and the behavior of the nurses
      and physicians to preserve the child's privacy. An information leaflet and a
      survey on symptoms is sent to parents before the test. Information is adapted to
      every age and aims to reduce parental anxiety towards the test and make them
      understand the need for the study. There are two premises for information: 1)
      every procedure will be explained to the child and parents, and 2) they will be
      told the truth. RESULTS: An enhanced cooperation has been noted following these
      guidelines. Between 5 and 8% of the studies performed are not evaluable due to
      lack of cooperation from the patient and only two children have totally refused
      the test in the last two years (0.2%). CONCLUSIONS: Cooperation among urologists
      and specialized nurses as well as attention towards the child's and parents'
      psychological factors can enhance the diagnostic yield of this test.

PMID- 7733684
TI  - [Endoscopy-assisted renovascular surgery].
AB  - OBJECTIVES: Laparoscopic surgery still has many impediments which render it
      impracticable or very difficult in many cases. In this article we describe in the
      laboratory the possibilities of performing it helped with a hand that has
      previously been introduced in the abdomen through a minilaparotomy. METHODS: Once
      the animal is in the lateral decubitus position, a longitudinal suprapubic
      incision of some 5 cm is done, through which the surgeons left hand is
      introduced. Then, together with the instruments, the kidney, its vessels, the
      aorta and vena cava are dissected. In one case the left renal artery was
      temporally clamped, divided and then sutured. RESULTS: This minimally invasive
      technique allowed in all the cases to accurately perform the operation in a very
      short time and with minimal risk. CONCLUSIONS: The main indication of this
      technique are the cases in which a large incision is required, as in large renal
      tumors or testicular cancer surgery. It is particularly useful in previously
      operated patients, or if a complication arises during a laparoscopy, or if a
      minilaparotomy is required as, in ileal conduits. This procedure also opens the
      door to a new approach to renovascular surgery.

PMID- 7733685
TI  - [Endoscopic cervicotomy: elective treatment in bladder neck sclerosis].
AB  - OBJECTIVES: The present study compared the efficacy of perimetric resection of
      the sclerotic ring (TR) and two-incision endoscopic cervicotomy (TC) for bladder
      neck sclerosis. METHODS: Fourteen cases (11 primary and 3 recurrence) underwent
      perimetric TR using a conventional 24 F curved loop resectoscope to excise the
      sclerotic diaphragm completely. In 11 cases (9 primary and 2 recurrence following
      previous perimetric (TR) two deep incisions were made at 5 and 7 o'clock with the
      Collins blade. Occasionally, the Sachse urethrotome had to precede the insertion
      of the conventional 24 F sheath. RESULTS: Of the 14 cases with bladder neck
      sclerosis that underwent perimetric TR, 5 (36%) recurred, while no recurrence was
      observed in the 11 patients treated by double TC. The results were assessed on
      the basis of the clinical findings and control flowmetry. CONCLUSIONS: Dysuria
      was the most common clinical symptom and was confirmed by flowmetry. Confirmation
      must be done endoscopically and preferably under anesthesia to permit treatment,
      if required, during the same session. TC is more reliable and TR is not advocated
      because of the high recurrence rate.

PMID- 7733686
TI  - [Obstructive uropathy as a complication of aortic disease and reconstructive
      peripheral vascular surgery: report of 4 cases and review of the literature].
AB  - OBJECTIVES: Ureteral injury can be a complication of peripheral vascular
      reconstructive surgery or aneurysm of the abdominal aorta. The present study
      analyses 4 cases of obstructive uropathy; 3 following peripheral vascular
      reconstructive surgery and 1 from aneurysm of the abdominal aorta. METHODS: All 4
      patients were prospectively evaluated. RESULTS: Both renal units were compromised
      in all 4 cases. The initial management consisted of internal urinary diversion
      with a double J catheter. Ureterolysis was performed in one case of unresolved
      uropathy secondary to prior bypass surgery. One case with uropathy due to
      infection of the vascular prosthetic graft required graft replacement.
      CONCLUSIONS: The risk of ureteral injury is likely to be seen more often due to
      the increasing number of operations on the vascular tree and enhanced survival of
      patients with aortic aneurysm. Prevention of the foregoing complication includes
      doing US and/or IVP early postoperatively and in the first 4 months following
      surgery. Patient management is initially conservative.

PMID- 7733687
TI  - [Factors influencing the consequences of disease on urologic patients].
AB  - OBJECTIVES: This study analyzed various factors that may affect social and
      personal consequences of disease in urological patients, as well as any possible
      relationships between these factors and disadvantageous situations they might
      produce. METHODS: A two-year retrospective study on patients of the University
      Hospital of Valladolid was conducted. The material used included a thorough
      analysis of case histories and questionnaires comprising all factors considered
      of interest by the most relevant Bodily Harm Valuers. The data obtained were
      processed and analyzed by the Statistics and Operations Research Departments of
      the University of Valladolid. RESULTS: In our study, sex and age were remarkably
      influential on sexual, economic and disablement damages. The different types of
      illnesses and the types of operations performed (non-surgical operations
      presented less consequences than surgical ones), as well as other factors such as
      distance from the patients' home to hospital, had a statistically significant
      correlation with the consequences of disease. CONCLUSIONS: We can detect certain
      disadvantageous situations through a previous study of the different variables
      that are collected in case histories, such as social, personal and economic
      circumstances. Thus, we can plan support programs in the future that will
      certainly reduce the consequences of disease.

PMID- 7733688
TI  - [Immunoprophylaxis of superficial tumors of the bladder with interferon alfa-2b.
      Our experience].
AB  - OBJECTIVE: The present study was conducted to determine the usefulness of
      prophylactic therapy with alpha 2b interferon for superficial bladder tumors.
      METHOD: Following complete TUR, alpha 2b infereron was administered to 36
      patients at a dose of 50 million IU weekly for 3 months and monthly for 9 months.
      Patients were evaluated every 3 months on the basis of their clinical and
      analytical data and the cystoscopic findings. RESULTS: Twenty-six patients
      completed treatment and were evaluable. The follow up and disease-free period was
      25.70 months. Recurrence was observed in 38.4% of the patients and tumor
      progression in 3.8%. CONCLUSIONS: Alpha 2b interferon is useful in the prevention
      of tumor recurrence. Its utility is similar to that of other drugs currently
      used.

PMID- 7733689
TI  - [Our experience with renal adenocarcinoma (I): epidemiologic data].
AB  - OBJECTIVES: The present study was conducted to review the epidemiological factors
      of patients with renal cell carcinoma. METHODS: We reviewed the familial, social,
      cultural, toxic, occupational and pathological factors of 229 patients who were
      diagnosed as having renal cell carcinoma between 1975 and 1992 at our hospital.
      RESULTS: As in other series, we found a greater predisposition in male patients
      around the seventh decade. However, unlike other studies, we observed a greater
      predisposition in the lower social and cultural levels and rural population. Of
      the epidemiological factors related to adenocarcinoma of the kidney, smoking was
      the most common in this series (41.8%), followed by high blood pressure (15.7%)
      and toxic-occupational factors (8.2%). We found no correlation between these
      factors and tumor stage or survival. CONCLUSIONS: Our data show a greater
      predisposition for renal cell carcinoma in male patients, around the seventh
      decade, in the lower social and cultural levels and rural population. Smoking,
      high blood pressure and occupational exposure to toxic agents were the most
      common epidemiological factors.

PMID- 7733690
TI  - [Our experience with renal adenocarcinoma (II): clinical course, diagnosis, and
      prognostic factors before surgical treatment].
AB  - OBJECTIVES: We evaluated the form of presentation, clinical features and
      analytical values and their relationship with survival in renal cell carcinoma
      patients and analyzed the efficiency of different diagnostic and staging
      procedures. METHODS: We reviewed the form of presentation, clinical features,
      staging procedures and analytical values of 229 consecutive renal cell carcinomas
      diagnosed at our hospital between 1975 and 1991. RESULTS: Malaise and weight loss
      or symptoms different from those of the classical triad (hematuria, pain and a
      flank mass) are factors of poor prognosis and lower survival. The time of
      presentation of symptoms does not influence prognosis. Computerized tomography
      was found to be the best imaging technique, with a low sensitivity and a high
      specificity in our experience. We have found a correlation between hypercalcemia
      and lower survival, but not for the more advanced tumoral stage. There was a
      correlation between the levels of hemoglobin and alkaline phosphatase and
      survival: patients with hemoglobin levels less than 14 g/dl or alkaline
      phosphatase levels greater than 85 U/l had a lower survival rate and a more
      advanced tumoral stage. CONCLUSIONS: Computerized tomography was found to be the
      best imaging technique. Symptoms different from those of the classical triad,
      malaise and weight loss, hypercalcemia, low levels of hemoglobin or high levels
      of alkaline phosphatase are factors of poor prognosis.

PMID- 7733691
TI  - [Our experience with renal adenocarcinoma (III): results of surgical treatment,
      other treatments. Survival analysis].
AB  - OBJECTIVES: Evaluation of survival and results of treatment of renal cell
      carcinoma. METHODS: We reviewed the records of 229 consecutive cases of renal
      cell carcinoma diagnosed at our hospital. In 178 surgical treatment was done to
      achieve cure and in 6 patients it was palliative. RESULTS: No statistical
      differences in survival were found according to the surgical approach, or
      extensive vs hilar lymphadenectomy, or in the presence or absence of venous
      involvement. There were statistical differences in survival depending on the
      tumor stage and an inverse correlation between survival and tumor size. Sixty
      nine cases received complementary treatments. Radiotherapy, alpha 2b interferon
      and vinblastine, resection of metastasis, or gestagen therapy failed to improve
      survival. No improvement in survival was achieved with palliative embolization,
      but it ameliorated local symptoms. The mean survival in patients with metastasis
      and without treatment was 5.5 months and there was no statistical difference in
      survival relative to the number of site of metastasis, or the number of affected
      viscera. The mean survival in patients that were not operated and had no
      metastasis was greater: 23.5 months. CONCLUSIONS: Surgery, regardless of the
      surgical approach or type of lymphadenectomy, is the only treatment that improves
      survival in renal cell carcinoma. Patients with metastasis receiving no treatment
      have a worse prognosis.

PMID- 7733692
TI  - [Echo-guided punction with pistol for extraction of retained urethral balloon
      catheters].
AB  - OBJECTIVES: We report our experience with a percutaneous technique for the
      removal of a balloon catheter retained within the bladder, using transrectal
      ultrasound and the biopsy gun. METHODS: Using ultrasound equipment with a
      transrectal probe of 5 mHz, we introduce the biopsy gun with an 18G needle guided
      by the probe. It is aimed at the retained balloon, which is deflated by punction.
      RESULTS: We carried out this technique successfully and without complications on
      three patients. CONCLUSIONS: We believe this technique is simple, efficient and
      quickly resolves the problem with minimum or no morbidity.

PMID- 7733693
TI  - [Adrenal hemangioma: unusual cause of retroperitoneal hemorrhage].
AB  - OBJECTIVES: Adrenal hemangiomas are rare tumors that are difficult to diagnose
      preoperatively. A case of retroperitoneal hemorrhage arising from adrenal
      hemangioma is described. This uncommon clinical manifestation prompted us to
      report on the present case and briefly review the scant literature on the
      diagnostic and therapeutic aspects. METHODS: The case described herein is that of
      a male patient who presented with hematoma in scrotum and penis that had appeared
      progressively with no previous trauma. The diagnosis was made by abdominal US and
      CT, which showed a retroperitoneal mass that appeared to be solid. An enlarged
      adrenal gland with tumoral "blush" was shown on selective vascular evaluation.
      RESULTS: En bloc excision of the adrenal gland, left kidney and spleen was
      performed. The histological analysis revealed adrenal hemangioma. CONCLUSIONS:
      Adrenal hemangioma is a rare tumor type with no clinical or biological symptoms
      of a functioning tumor that is generally diagnosed with difficulty
      preoperatively. The differential diagnosis must be made to distinguish adenoma,
      carcinoma, nonfunctioning adrenal pheochromocytoma and spontaneous hemorrhage.

PMID- 7733694
TI  - [Prenatal torsion of the spermatic cord].
AB  - OBJECTIVES: Considerations on a case of prenatal torsion of the spermatic cord.
      METHODS: Review of cases reported in the literature. RESULTS: Testicular torsion
      rarely occurs in the perinatal period. Nearly a hundred cases with surgical
      confirmation have been reported. CONCLUSIONS: Prenatal torsion is almost
      exclusively extravaginal, while postnatal extravaginal torsion is extremely rare.
      The possibility of finding a viable testis is extremely remote. The treatment
      should be directed at minimizing any potential perioperative complications by
      scheduling an elective operation after the neonate is medically stable.

PMID- 7733695
TI  - [Bilateral renal angiomyolipoma associated with tuberous sclerosis: conservative
      surgical treatment].
AB  - OBJECTIVES: To evaluate the efficacy of surgical treatment of angiomyolipoma.
      METHODS: We present a case of multiple, bilateral renal angiomyolipoma in a
      patient with tuberous sclerosis, who was treated by conservative surgery.
      RESULTS: The patient is clinically asymptomatic one year after surgery and both
      kidneys are functioning correctly as shown by pyelography. CONCLUSIONS: We
      recommend conservative surgical treatment of symptomatic or developing
      angiomyolipomas.

PMID- 7733696
TI  - [Renal agenesis, cranial blind ureter and ureterocele. Report of a case].
AB  - OBJECTIVES: We report a case of associated malformations in a young male with
      recurrent epididymitis. METHODS: In our study we used the following techniques:
      ultrasound, intravenous urography, retrograde pyelography, computed tomography
      and cystoscopy. RESULTS: We observed three coexisting congenital malformations:
      renal agenesis, cranial blind-ending ureter and ureterocele. CONCLUSIONS:
      Different urologic malformations are usually found in association. In our view
      only symptomatic ureteroceles require treatment.

PMID- 7733697
TI  - "A half-dead thing..."?

PMID- 7733698
TI  - Up to thirty-year survival after aortic valve replacement in the small aortic
      root.
AB  - Aortic valve replacement (AVR) in the small aortic root has been reported to be
      associated with obstruction of left ventricular output. This study was designed
      to investigate the determinants of long-term survival after the implantation of
      small size prostheses. From September 1961 to December 1993, 2,977 patients
      underwent isolated aortic valve replacement at our institution. Of these
      patients, 447 who were older than 18 years received small size (21 mm or less)
      prostheses. Long-term survival was investigated in the 404 patients who survived
      operation (more than 30 days) with 92% follow-up completeness (mean +/- deviation
      7.1 +/- 6.4; maximum, 31 years). The age was younger than 50 years in 62
      patients, 50 to 59 years in 60, 60 to 69 years in 99, 70 to 79 years in 138, and
      80 to 94 years in 45; 67% were men. Thirty patients (7%) had previous AVR.
      Prosthesis usage included early Starr-Edwards models in 130 (32%), current Starr
      Edwards (model 1260 since 1969) in 50 (12%), Carpentier-Edwards (porcine) in 113
      (28%), and other prostheses in 111 patients (27%). One hundred sixteen patients
      (26%) had concomitant coronary artery bypass grafting (CABG). Eleven variables
      (age divided as above, sex, preoperative functional class, body surface area
      [BSA], small BSA [less than 1.6, 1.7, 1.8, or 1.9 m2], period of operation,
      previous AVR, type of prosthesis, size of prosthesis, concomitant CABG, and re
      replacement) were investigated with regard to the long-term survival by the
      Kaplan-Meier method, and age, concomitant CABG, and type of prosthesis were
      significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733699
TI  - Immunostains for blood group antigens lack prognostic significance in T1 lung
      carcinoma.
AB  - Recent reports have suggested that the retention of blood group antigen
      expression on tumor cells may be an important prognostic factor for survival.
      From 1986 to 1991, 136 patients underwent operative resection for their T1 N0 non
      small cell lung carcinoma. One hundred twenty tissue blocks were available for
      antigen testing, and the histologic types were as follows: adenocarcinoma (73
      patients), squamous cell (39 patients), large cell/undifferentiated (7 patients),
      and mucoepidermoid (1 patient). Follow-up is complete for all patients (mean, 41
      months). This distribution of patients among the blood groups was as follows: A,
      56 (47%); O, 53 (44%); B, 9 (7.5%), and AB, 2 (1.7%). Immunostaining was
      performed for A, B, and H blood group antigens. The 5-year actuarial survival in
      the blood group A patients (53%) did not differ significantly from that in the
      blood group O patients (59%). Similarly, when tumors were examined for their
      respective antigens, no significant differences were found in the 5-year survival
      of either blood group A or O patients between the tumors that retain and those
      that lose blood group antigen expression. Retention or loss of blood groups A or
      O antigen expression does not predict survival in patients with early-stage lung
      carcinomas.

PMID- 7733700
TI  - Clinical pathways can be based on acuity, not diagnosis.
AB  - The standardization of medical practice is gaining acceptance as a technique for
      controlling length of stay and hospital charges, while maintaining quality. Most
      clinical pathways address specific diagnoses or procedures, but we have developed
      a new approach in which pathways for cardiac care are based on acuity. All
      congenital cardiac surgical care rendered at Columbus Children's Hospital now
      falls within one of four such clinical pathways. This simplified approach is easy
      to use and has been well accepted. Our experience in a group of 107 consecutive
      patients treated in this fashion is described. The results of variance analyses,
      along with length of stay and charge data, are presented to demonstrate the
      degree to which resource utilization can be standardized in this widely variable
      group of patients whose problems were made cohesive by classification according
      to acuity level. We conclude that the resultant standardization offers
      considerable advantages for the managed care environment.

PMID- 7733701
TI  - Arrhythmogenic ventricular aneurysms unrelated to coronary artery disease.
AB  - Malignant ventricular tachycardia occurs most frequently in patients with
      coronary artery disease who have had a previous myocardial infarction and in whom
      a ventricular aneurysm subsequently develops in the scarred section of
      myocardium. Ventricular tachycardia in the presence of normal coronary arteries
      and a left ventricular aneurysm is unusual and can be refractory to medical
      therapy. We retrospectively reviewed our experience of 10 patients treated at our
      institution from 1983 to 1993. Age ranged from 22 to 76 years, and all patients
      presented with sustained ventricular tachycardia. All patients underwent complete
      electrophysiologic testing. Cardiac catheterization was performed in 9 patients,
      and each had normal coronary artery anatomy without evidence of significant fixed
      lesions. A left ventricular aneurysm, diagnosed by either echocardiography,
      thoracic cine computed tomography or magnetic resonance imaging, or ventricular
      angiography was present in all patients. Ventricular tachycardia could not be
      suppressed pharmacologically in 7 of 10 patients using multiple agents including
      procainamide, quinidine, flecanide, tocainide, propaferone, and amiodarone. Six
      patients were treated surgically by intraoperative electrophysiologic mapping,
      endocardial resection of foci, and left ventricular aneurysmectomy. An
      implantable cardiac defibrillation device was implanted in 2 patients. One
      patient died on the second postoperative day after simultaneous mapping -guided
      aneurysmectomy and implantable cardioverter defibrillator placement. There was
      one late postoperative death. All other surgically treated patients had
      postoperative electrophysiologic studies demonstrating no inducible ventricular
      tachycardia, and these patients remain without antiarrhythmic therapy in follow
      up extending from 29 to 86 months (mean, 56 months).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7733702
TI  - Multimodality therapy for adenocarcinoma of the esophagus.
AB  - Few reports exist detailing results of multimodality treatment for adenocarcinoma
      of the esophagus. We have treated 28 such patients using a preoperative regimen
      consisting of two courses of cisplatin and 5-fluorouracil with radiation (either
      3,000 or 3,600 cGy). There were 25 men and 3 women (mean age, 62.9 years; range,
      35 to 86 years), and 16 patients were known to have Barrett's esophagus.
      Dysphagia was present for a mean of 2.7 months, and the average weight loss was
      6.5 kg. Tumors ranged from 2 to 10 cm in length (mean, 5.2 +/- 1.8 cm) with
      American Joint Committee on Cancer clinical stage I in 2 patients, stage II in 19
      patients, and stage III in 7. Dysphagia improved in 23 patients (82%), and in 8
      (29%) no tumor was detected during radiologic and endoscopic staging after
      neoadjuvant therapy. Four patients refused operation. Esophagectomy via standard
      Ivor Lewis approach was accomplished in 20 of 24 patients (87%) undergoing
      operation. There were no operative deaths, and mean hospital stay was 15.5 +/-
      11.6 days. Four patients (17%) were complete responders with no tumor in the
      resected specimen. Actuarial survival in the 28 patients at 1, 2, and 3 years is
      71%, 28%, and 20% respectively. Of the 20 esophagectomy patients, 6 are alive
      with no evidence of disease at 10, 50, 54, 70, 77, and 84 months. Three of these
      were complete responders. Only 1 of the 8 patients no undergoing resection is
      alive at 16 months with no evidence of disease after further radiotherapy and
      chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733703
TI  - Clinical experience with nonthoracotomy cardioverter defibrillators.
AB  - A new generation of defibrillators has been introduced that do not require a
      thoracotomy. The purpose of this report was to examine 100 consecutive
      nonthoracotomy implantations at our institution and compare them with a series of
      102 patients undergoing thoracotomy implantations by the same surgeon over a 4
      year period between August 1989 and September 1994. The two groups were
      comparable for age, sex, comorbidity, cardiac disease status, ejection fraction,
      and electrophysiologic presentation. Nonthoracotomy systems were implanted
      successfully in 94% of patients. Patients undergoing a nonthoracotomy
      implantation had significantly shorter intensive care unit (1.7 +/- 1.7 versus
      3.3 +/- 3.9 days; p < 0.005) and postoperative stays (5.0 +/- 2.8 versus 9.5 +/-
      5.6 days; p < 0.001) than patients undergoing a thoracotomy approach. This was
      due to a significant decrease in the incidence of postoperative complications
      from 29% in the thoracotomy group to 11% in the nonthoracotomy group (p < 0.001).
      There was no significant difference in overall mortality rates. Nonthoracotomy
      systems are implantable in the majority of patients and are associated with less
      morbidity and shorter hospital stays than traditional thoracotomy approaches.

PMID- 7733704
TI  - Video-assisted thoracic surgery for the anterior approach to the thoracic spine.
AB  - Standard anterior approach to the thoracic spine is by a posterolateral
      thoracotomy. Because of the morbidity associated with this incision, video
      assisted thoracic surgery (VATS) has been used as a less invasive approach for
      many intrathoracic disease processes. We have applied VATS for anterior access to
      the thoracic spine. From April 1991 to September 1994, 95 patients underwent
      thoracic spine procedures using thoracoscopy as the sole method of anterior
      approach. Procedures performed include discectomy for herniation (n = 57),
      multilevel discectomy for correction of spinal deformity (27), corpectomy (9),
      and drainage of intervertebral disc space abscess (2). All levels of the thoracic
      spine from the T2-T3 level to the T12-L1 interspace were approached. Forty-four
      procedures were performed through the left side of the chest and 41 through the
      right. The planned procedure was accomplished by VATS in all but 1 patient who
      required conversion to an open procedure because of scarring from a previous
      spine procedure. Mean operative time was 2 hours 24 minutes (range, 45 minutes to
      5 hours 10 minutes). Average chest tube duration was 1.4 days, and mean length of
      stay was 4.82 days (range, 2 to 21 days). Complications included intercostal
      neuralgia (6), atelectasis (5), excessive epidural blood loss (2,500 mL; 2) and
      temporary paraparesis in a scoliosis patient related to operative positioning. We
      conclude that VATS offers a new, less morbid anterior approach to the thoracic
      spine. Although there is a significant learning period, most procedures requiring
      an anterior access can be performed safely by this technique. The VATS approach
      mandates an expanded role for the thoracic surgeon in operative spine disease.

PMID- 7733705
TI  - Retrograde cerebral perfusion during profound hypothermia and circulatory arrest
      in pigs.
AB  - The purpose of this study was to evaluate the use of retrograde cerebral
      perfusion via the superior vena cava during profound hypothermia and circulatory
      arrest (CA) in pigs. In three groups of 5 pigs each, group A (control) underwent
      cardiopulmonary bypass and normothermic CA for 1 hour, group B underwent
      cardiopulmonary bypass, profound hypothermia, and CA (15 degrees C
      nasopharyngeal) for 1 hour, and group C underwent the same procedure as group B
      plus retrograde cerebral perfusion. In group A none awoke. In group B, 2 of 5 did
      not awake and 3 of 5 awoke unable to stand, 2 with perceptive hind limb movement
      and 1 moving all extremities. In group C all awoke, 4 of 5 able to stand and 1 of
      5 unable to stand but moving all limbs. In neurologic evaluation group B had
      significantly lower Tarlov scores than group C (p = 0.0090). Group B mean wake-up
      time, plus or minus standard error of the mean, was 124.6 +/- 4.6 minutes versus
      29.2 +/- 5.1 in group C (p = 0.0090). In group B late phase CA cerebral blood
      flow dropped 30.9% +/- 4.8%, but in group C it rose 24.7% +/- 9.3% (p = 0.0007,
      pooled variance t test, two-tailed). In group B late phase CA brain oxygenation
      decreased 46.0% +/- 13.9% but it increased 26.1% +/- 5.4% in group C (p =
      0.0013). This difference was reduced somewhat during rewarming (B, -21.2% +/-
      14.9%; C, 16.4% +/- 4.7%; p = 0.043). Group B rewarming jugular venous O2
      saturation was 30.8% +/- 2.5% versus 56.0% +/- 4.4% in group C (p = 0.0011). We
      conclude that in pigs retrograde cerebral perfusion combined with profound
      hypothermia during CA significantly reduces neurologic dysfunction, providing
      superior brain protection.

PMID- 7733706
TI  - Double-valve replacement with Medtronic-Hall or St. Jude valve.
AB  - To define better the performance of the bileaflet St. Jude and the tilting-disc
      Medtronic-Hall valves, we retrospectively analyzed 122 patients (St. Jude, 80
      patients; Medtronic-Hall, 42 patients) who received simultaneous aortic and
      mitral replacement from May 1984 until June 1994. The two groups were not
      different with respect to preoperative clinical and hemodynamic parameters and
      New York Heart Association functional class. The hospital mortality and late
      mortality were not significantly different. Risk analysis identified advanced age
      and previous myocardial revascularization as predictors of operative death.
      Follow-up was complete in 96 of 103 hospital survivors (93%) and was similar in
      both groups. The actuarial survival, linearized rates of valve-related
      complications, and actuarial freedom from valve-related complications were
      similar in both cohorts. The presence of coronary artery disease negatively
      influenced the actuarial survival after simultaneous aortic and mitral valve
      replacement. Postoperative New York Heart Association functional class was not
      significantly different in either group. These data indicate that the Medtronic
      Hall and St. Jude prostheses are not significantly different with respect to
      their clinical performance and valve-related complications for simultaneous
      double-valve replacement.

PMID- 7733707
TI  - Primary bidirectional superior cavopulmonary shunt in infants between 1 and 4
      months of age.
AB  - The performance of a primary bidirectional superior cavopulmonary shunt procedure
      in early infancy is attractive because it minimizes the number of operations
      needed before a Fontan procedure, avoids ventricular volume overload and its
      sequelae, and eliminates pulmonary artery distortion. However, concerns over
      elevated or labile pulmonary vascular resistance have limited its use in the
      first few months of life. Nine patients aged 1 to 4 months (5 patients, < 2
      months) have undergone a primary bidirectional superior cavopulmonary shunt
      procedure between October 1992 and March 1994. Primary diagnoses were tricuspid
      atresia (n = 4), asplenia syndrome (n = 2), polysplenia syndrome (n = 1), double
      outlet right ventricle (n = 1), and double-inlet left ventricle (n = 1).
      Associated lesions of immediate surgical importance were total anomalous
      pulmonary veins (n = 2), a restrictive atrial septum (n = 4), bilateral superior
      venae cavae (n = 5), and patent ductus arteriosus (n = 5). The surgical procedure
      consisted of unilateral (n = 4) or bilateral (n = 5) bidirectional superior
      cavopulmonary shunt and the repair of associated lesions. Of significance, in 4
      of our first 5 patients a very limited additional source of pulmonary blood flow
      was provided because of a low arterial oxygen tension immediately after
      cardiopulmonary bypass. Pleural effusions developed in 2 of these 4 patients. In
      subsequent patients cardiopulmonary bypass was not used whenever possible or, if
      it was needed, use of an extra source of pulmonary blood flow was
      avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733708
TI  - Cardiac storage with University of Wisconsin solution and a nucleoside-transport
      blocker.
AB  - Findings from previous investigations conducted at this institution and others
      have suggested that University of Wisconsin solution (UWS) is preferable for the
      prolonged hypothermic storage of hearts before transplantation. The benefit seen
      with UWS may in part be related to the inclusion of adenosine (5 mmol/L) in the
      UWS. To investigate whether further manipulations of adenosine metabolism might
      enhance myocardial protection, studies were initially conducted using cultured
      myocytes, followed by confirmatory experiments using isolated rat hearts.
      Cultured human ventricular myocytes (7 to 8 dishes/group) were stored for 12
      hours at 0 degrees C in unmodified UWS or UWS supplemented with increasing
      concentrations (1 to 100 mumol/L) of the nucleoside-transport blocker p
      nitrobenzylthioinosine. The adenosine triphosphate concentrations were found to
      be enhanced with nucleoside-transport inhibition, with the best results achieved
      with the 1- and 3-mumol/L groups (control, 3.37 +/- 0.41 nmol/micrograms DNA;
      UWS, 2.89 +/- 1.31 nmol/micrograms DNA; 1 mumol/L, 5.91 +/- 3.23 nmol/micrograms
      DNA; 3 mumol/L, 7.86 +/- 3.45 nmol/micrograms DNA; p < 0.05 versus control or UWS
      group). Isolated rodent hearts from Sprague-Dawley rats were prepared on a
      Langendorff apparatus with an intraventricular balloon and subsequently stored
      for 8 hours at 0 degrees C in unmodified UWS (13 hearts/group) or UWS
      supplemented with 1 or 3 mumol/L of p-nitrobenzylthioinosine (9 to 10
      hearts/group).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733709
TI  - Tricuspid valve regurgitation attributable to endomyocardial biopsies and
      rejection in heart transplantation.
AB  - In the present report the prevalence, severity, and risk factors of tricuspid
      valve regurgitation (TR) in 251 heart transplant recipients have been analyzed
      retrospectively. Tricuspid valve function was studied by color-flow Doppler
      echocardiogram and annual heart catheterization. The presence or severity of TR
      was graded on a scale from 0 (no TR) to 4 (severe). Additional postoperative data
      included rate of rejection, number of endomyocardial biopsies, incidence of
      transplant vasculopathy, and preoperative and postoperative hemodynamics. The
      incidence of grade 3 TR increases from 5% at 1 year to 50% at 4 years after
      transplantation. Multivariate analysis showed rate of rejection and donor heart
      weight to be significant risk factors. The ischemic intervals as well as the
      preoperative and postoperative pulmonary hemodynamics did not affect the severity
      or prevalence of TR. These results indicate that various factors appear to have
      an impact on the development of TR and that the prevalence might be lowered by a
      reduction of the number of biopsies performed and when possible, oversizing of
      donor hearts.

PMID- 7733710
TI  - Operation for unstable angina pectoris: factors influencing adverse in-hospital
      outcome.
AB  - Coronary artery bypass grafting for the treatment of unstable angina is still
      associated with increased operative risk and postoperative morbidity. The impact
      of the extended use of arterial grafts on early results is incompletely defined.
      In a 7-year period (1986 to 1993), 474 patients (average age, 65 years; range, 34
      to 85 years) underwent coronary artery bypass grafting for the treatment of
      unstable angina. Sixty-eight patients were operated on emergently and 406
      urgently. They received an average of 3.0 distal anastomoses (range, 1 to 6).
      Seventy-nine patients had exclusively venous grafts, 316 had one internal
      thoracic artery graft, 79 had bilateral internal thoracic artery grafts, and 20
      had inferior epigastric artery grafts. Sequential internal thoracic artery
      grafting was performed in 70 patients. Redo operations were performed in 26
      patients. Thirty-four patients (7.2%) experienced a new myocardial infarction.
      Eighty-nine patients (18.8%) had an intraaortic balloon pump inserted
      preoperatively, intraoperatively, or postoperatively. Eight patients (1.7%) died
      intraoperatively and 24 patients (5.1%) died postoperatively. Seventy-seven
      patients (16.2%) had an adverse outcome, as shown by the need for an intraaortic
      balloon pump (intraoperatively or postoperatively) or hospital death, or by both.
      Forty variables were examined by multivariate analysis for their influence on the
      occurrence of an adverse outcome. Aortic cross-clamp time (p = 0.0004), transfer
      from the intensive care unit (p = 0.0023), female sex (p = 0.0023), operation
      performed in early years (p = 0.0041), left ventricular aneurysm (p = 0.0068),
      the number of diseased coronary vessels (p = 0.0312), and reoperation (p =
      0.0318) were all found to be significant independent predictors of increased
      risk.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733711
TI  - Assessment of the value of the immediate postoperative chest radiograph after
      cardiac operation.
AB  - The value of the immediate postoperative chest radiograph upon a patient's return
      to the intensive care unit after a cardiac surgical procedure is uncertain. This
      study represents a prospective analysis of the immediate postoperative radiograph
      in 100 consecutive adult patients undergoing cardiac operations. In 11 patients
      it was found that the routine postoperative radiograph was of value when it was
      necessary either to clarify or confirm clinical findings or to check the position
      of an intraaortic balloon catheter. For those chest radiographs that were deemed
      unnecessary, only one of 89 were found to be of clinical value. Furthermore, in
      those situations in which an emergency radiograph was obtained, the routine
      radiograph was not found to be contributory to patient management. We conclude
      that the policy of obtaining routine, immediate postoperative chest radiographs
      in the absence of a specific clinical indication provides virtually no additional
      clinical yield. Residents should therefore request radiographs only to check the
      position of an intraaortic balloon catheter, and to clarify or confirm a clinical
      diagnosis.

PMID- 7733712
TI  - Endothelial dysfunction in venous pulmonary hypertension in the neonatal piglet.
AB  - In a group of neonatal piglets an increase in pulmonary arterial pressure was
      obtained within 2 weeks after a partial mechanical obstruction of the left atrium
      by a balloon catheter. Mean pulmonary artery pressure in the hypertensive animals
      (n = 6) was 24 +/- 2 mm Hg as compared (p < 0.01) with 15 +/- 1 mm Hg in controls
      (n = 6) or 9 +/- 2 mm Hg in sham-operated piglets (n = 6). Cardiac index was
      reduced in hypertensive versus control and sham groups: 0.15 +/- 0.01 versus 0.32
      +/- 0.05 and 0.29 +/- 0.04 L.min-1.kg-1 (p < 0.05), respectively. There was no
      detectable difference on histologic examination in the pulmonary arteries between
      the three groups. Right ventricular hypertrophy was observed in the group with
      pulmonary hypertension. In hypertensive piglets, isolated conduit pulmonary
      arteries did not relax when stimulated with acetylcholine; they always relaxed to
      sodium nitroprusside. These data suggest that the first stages of perturbations
      reported during pulmonary venous hypertension occur at the level of the pulmonary
      vascular endothelium. This neonatal model of pulmonary hypertension is simple to
      perform and might be useful for further investigations.

PMID- 7733713
TI  - Giant lymph node hyperplasia (Castleman's disease) in the chest.
AB  - We have experienced 7 cases of giant lymph node hyperplasia in the chest from
      1981 to 1992. The ages of the 1 male and 6 female patients ranged from 9.9 to
      40.4 years (mean age, 29.2 +/- 10.4 years). In 4 patients, a mass was discovered
      in routine radiographs. Focal calcification suggesting continual enlargement over
      a long time was noted in 1 patient. The sites of lesions were unusual in 2
      patients (intercostal space and intrapulmonary fissure). All patients underwent
      surgical removal of the mass. Five cases had typical features of the hyaline
      vascular type, and 2 cases revealed a mixture of the hyaline-vascular type and
      the plasma-cell type. Follow-up was available in all patients (mean follow-up,
      31.9 months). In 1 patient, recurrence was observed 9 years after surgical
      removal. In general, giant lymph node hyperplasia can occur anywhere in the
      chest, grow without symptoms, and recur in spite of complete resection. Surgical
      resection and close follow-up are advised.

PMID- 7733714
TI  - Thoracoscopic debridement of loculated empyema thoracis in children.
AB  - The appropriate management of multiloculated empyema thoracis remains
      controversial. During a 7-month period, we have managed multiloculated empyema
      with early thoracoscopic debridement in three consecutive pediatric patients.
      Chest tubes were removed 7 +/- 1 (mean +/- standard deviation) days after
      thoracoscopy and discharge from hospital was on postoperative day 8 +/- 1. We
      suggest that early thoracoscopic debridement of multiloculated empyema thoracis
      in children is safe and efficacious.

PMID- 7733715
TI  - Coronary artery bypass grafting within 30 days of an acute myocardial infarction.
AB  - Risks and benefits of performing coronary artery bypass grafting (CABG) within 30
      days of an acute myocardial infarction (AMI) were examined. In 642 patients
      operated on between January 1988 and December 1993, emergent CABG was performed
      in 46 patients for cardiogenic shock mainly for failed thrombolysis in patients
      with an evolving AMI. The remaining patients underwent urgent (< 72 hours) or
      elective (> 72 hours) revascularization for failed percutaneous transluminal
      coronary angioplasty (n = 73), postinfarction angina (n = 381), vein graft
      stenosis (n = 100), and complications after an AMI (n = 42). In patients who
      underwent primary CABG for an uncomplicated AMI, the infarct was subendocardial
      in 68, anterolateral or septal in 200, inferior or posteroinferior in 200, and
      posterolateral in 32 patients. Early mortality (< 30 days) was 5.9% for the
      entire series and 0%, 4.5%, 4.5%, 29%, 9%, 8%, 10%, and 26% for the subsets of
      patients with subendocardial infarct, anterolateral or septal infarct, inferior
      or posteroinferior infarct, ischemic mitral regurgitation, left ventricular
      aneurysm, redo CABG, age more than 70 years, and left ventricular ejection
      fraction less than 0.30, respectively. By multivariate analysis, independent
      predictors of early mortality were left ventricular ejection fraction less than
      0.30, age more than 70 years, and cardiogenic shock.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7733716
TI  - Long-term preservation of vascular endothelium and smooth muscle.
AB  - This study was performed in organ baths on 400 ring segments of infrarenal aorta
      taken from 40 Sprague-Dawley rats that had been randomized into five groups.
      Contractility was tested with the thromboxane analogue U-46619. Acetylcholine was
      used to elicit endothelium-dependent relaxing factor (EDRF). The results obtained
      from vessels preserved at 4 degrees C for 6, 12, 24, and 36 hours were compared
      with those from autologous vessels studied immediately after harvesting. Vessels
      preserved in Euro-Collins solution showed a 46% (p < 0.01) decrease in
      contractility after 12 hours of storage; after 24 hours only weak contractions
      could be elicited, and after 36 hours they had lost their ability to contract.
      The EDRF function was slightly reduced after 12 hours and could not be
      investigated after 24 and 36 hours. With the University of Wisconsin solution
      (UW) and the low-potassium-dextran-glucose solution Perfadex no decrease in
      contractility was seen in the first 24 hours, but at 36 hours the vessels
      preserved in UW had lost 40% (p < 0.01) and those preserved in Perfadex 30% (p <
      0.05) of their contractility. The EDRF function was significantly reduced by
      about 15% after 6, 12, and 24 hours in both the UW and the Perfadex groups. At 36
      hours, vessels stored in Perfadex had lost 41% (p < 0.001) and those stored in UW
      17% (p < 0.01) of their EDRF function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733717
TI  - Novel technique to bioassay endocardium-derived nitric oxide from the beating
      heart.
AB  - Nitric oxide is a potent vasodilator and antiplatelet substance released by the
      vascular endothelium. In the current study, isolated rabbit hearts were perfused
      retrograde in the aortic root with a balanced salt solution using a Langendorff
      technique. To perfuse the right cardiac chambers, an inflow cannula was placed in
      the superior vena cava and an outflow cannula in the right ventricular apex via
      the pulmonary artery. To detect endocardial vasodilator production, right heart
      perfusate was used to bathe a "bioassay" segment of canine coronary artery
      denuded of endothelium. Perfusate from unstimulated hearts did not alter smooth
      muscle tone in the bioassay tissue. Calcium inophore, a potent stimulus for
      endothelial nitric oxide production, produced relaxation of the bioassay smooth
      muscle when added to the cardiac perfusate but not when applied directly to the
      bioassay segment. Cardiac effluent vasodilator activity was abolished by removal
      of the endocardium or addition of nitric oxide synthesis inhibitors, but not by
      prostanoid inhibitors. These experiments describe a practical method to bioassay
      endocardial nitric oxide production in the beating heart.

PMID- 7733718
TI  - Cerebral microemboli during coronary artery bypass using different cardioplegia
      techniques.
AB  - Larger numbers of microemboli detected by transcranial Doppler echocardiography
      have been linked to adverse neuropsychological outcome after coronary artery
      bypass grafting. Differences in neurologic outcome have been attributed to
      different cardioplegia techniques. Transcranial Doppler-detected microembolic
      events were recorded during coronary artery bypass grafting using different
      cardioplegia techniques. Patients received cold antegrade (n = 20), warm
      antegrade (n = 17), or warm retrograde (n = 20) cardioplegia. Continuous
      monitoring was divided into stages: aortic cannulation, initiation of
      cardiopulmonary bypass, aortic cross-clamping, aortic declamping and
      decannulation until chest closure. Rate of embolic events and number of total and
      immediate embolic events were tabulated. Total embolic events ranged from 22 to
      2,072 per patient and were similar among groups. The rate and total at each stage
      were similar. Total embolic events were highest during aortic clamping; the rate
      was highest at initiation of bypass. The immediate embolic events were higher in
      the warm retrograde group than both antegrade groups at aortic declamping. In
      summary, a high total and rate of embolic events were detected and differences
      between cardioplegia techniques were detected.

PMID- 7733719
TI  - Use of cardiac troponin I as a marker of perioperative myocardial ischemia.
AB  - Troponin I is a contractile protein comprising three isoforms, two related to the
      skeletal muscle and one to the cardiac fibers. Cardiac troponin I (CTn I) is
      specific, without any cross-reactivity with the other two. Several studies have
      demonstrated its release after acute myocardial infarction. In contrast, CTn I
      never has been found in a healthy population, marathon runners, people with
      skeletal disease, or patients undergoing non-cardiac operations. Thus, CTn I is a
      more specific marker of cardiac damage than common serum enzymes. It is also more
      sensitive, allowing diagnosis of perioperative microinfarction and detection of
      acute myocardial infarction much earlier after the onset of ischemia (4 hours).
      Using a rapid one-step assay, we measured the release of CTn I in two groups of
      patients after operation: 20 with calcified aortic stenosis and normal coronary
      arteries (aortic valve replacement group and control group) and 20 undergoing
      coronary artery bypass grafting. In the overall population CTn I peaked at hour 6
      and practically disappeared after day 5. Mean values were higher in the coronary
      artery bypass grafting group. In the aortic valve replacement group, a positive
      correlation was found between aortic cross-clamping time and CTn I, which is a
      reliable marker of cardiac ischemia during heart operations and can be used to
      evaluate cardioprotective procedures.

PMID- 7733720
TI  - Operation for type A aortic dissection: introduction of retrograde cerebral
      perfusion.
AB  - Circulatory support during operation for type A aortic dissection is
      controversial among many medical centers. In the last 21 years, 100 patients with
      type A aortic dissection underwent 102 operations including 2 reoperations, and
      29 patients showed Marfan's syndrome. During operation, no cerebral perfusion
      technique was used through February 1985 (period I), antegrade cerebral perfusion
      was applied since March 1985 (period II), and retrograde cerebral perfusion was
      introduced in November 1990 (period III). Surgical results were compared among
      these subgroups. Operative mortality was 12.1% in 33 chronic and 57.1% in 7 acute
      patients in period I, 11.1% in 27 chronic and 54.5% in 11 acute patients in
      period II, and 6.7% in 15 chronic and 0% in 9 acute patients in period III
      (period II versus III; p = 0.04). Retrograde cerebral perfusion decreased
      permanent brain complications. The 5-year actuarial survival was 59.7% in period
      I and 63.2% in period II (not significant), and the 3-year survival of period III
      was 91.7%. Actuarial survival of period III was significantly higher than those
      of periods I and II (p < 0.05). Surgical repair of aortic arch with cerebral
      perfusion techniques reduced the residual aneurysms. These results show that
      surgical results of type A aortic dissection in this series improved with the
      introduction of retrograde cerebral perfusion and extended surgical procedures.

PMID- 7733721
TI  - Operation for type B aortic dissection: introduction of left heart bypass.
AB  - Various support techniques for surgical treatment of type B aortic dissection
      have been used and recommended in many medical centers. In the last 21 years, 55
      patients with type B aortic dissection underwent 65 operations including 10
      reoperations, and 10 cases showed Marfan's syndrome. As circulatory support
      during operation, venoarterial bypass mainly was used until March 1987 (period I)
      and low-dose heparinized left heart bypass was applied since April 1987 (period
      II). Surgical results were compared among subgroups by the Kaplan-Meier actuarial
      method and Cox-Mantel statistical analysis. After the operation, early mortality
      was 27.3% in 33 patients in period I and 9.4% in 32 patients in period II (p =
      0.06). The incidence of fatal hemorrhagic complications was decreased
      significantly by using the left heart bypass technique (p < 0.02). The 5-year
      actuarial survival of type B dissection was 60.6% in period I and 79.2% in period
      II (p = 0.07). These results suggest that surgical results of type B aortic
      dissection in this series might be improved with the introduction of left heart
      bypass and extended surgical procedures.

PMID- 7733722
TI  - Unoperated aortic aneurysm: a survey of 170 patients.
AB  - From 1984 to 1993, 1,053 patients were admitted with aortic aneurysm (AA) and 170
      (15%) were not operated on. The most frequent reason for nonoperative management
      was presumed technical inoperability. Survivals for patients with thoracic,
      thoracoabdominal, and abdominal AA were comparable. No significant differences in
      survival for patients with dissecting and nondissecting AA were detected. In all,
      132 patients (78%) died and 78 (59%) of them died of rupture. Mean time to
      rupture was 1,300 +/- 8 days. Cumulative 5-year hazard of rupture for the
      dissecting AA was twice that of the nondissecting (p < 0.001). Hazards of rupture
      for type A and B dissections were comparable. Diameter of 6 cm or greater was
      associated with a fivefold increase in cumulative hazard of rupture (p < 0.001).
      Diameter of AA, incidence of renal failure, and arterial hypertension were
      predictive of mortality, whereas the first two variables were predictive of
      rupture. In conclusion, because the majority of patients in all subgroups died of
      rupture, all patients should be recognized as candidates for surgical treatment.
      Present data justify aggressive approach to the patient with AA 6 cm or more in
      diameter and type A dissections. The results suggest that type B dissections may
      have a more favorable course if operated on, but a prospective, randomized study
      is necessary to confirm this observation. We believe that older patients and
      those with a small aneurysm may benefit from early, elective operation.

PMID- 7733723
TI  - Postoperative abdominal complications in cardiopulmonary bypass patients: a case
      controlled study.
AB  - Intraabdominal complications (IAC) after cardiopulmonary bypass often are
      difficult to diagnose and are associated with high mortality (13% to 67%). From
      1984 to 1991 we retrospectively analyzed 53 patients undergoing cardiopulmonary
      bypass for coronary artery bypass grafting, valve reconstruction, or arch
      reconstruction who experienced 55 episodes of IAC and compared them with matched
      control patients (matched for operation, age, and sex). The overall incidence of
      IAC was 0.65%. Univariate analysis identified the following preoperative
      variables as significantly (p < 0.05) increasing the risk of IAC: history of
      congestive heart failure, chronic renal failure, and more than three medical
      problems. A history of congestive heart failure was the most powerful predictor
      by multivariate analysis (p = 0.045). Early postcardiopulmonary bypass
      complications were increased significantly in IAC patients. These included acute
      renal failure (p < 0.0001), cerebrovascular accidents (p < 0.03), and lower
      extremity ischemia (p < 0.05). Twenty-eight of 38 laparotomies performed were
      diagnostic. However, analysis of 58 combined clinical, radiologic, and laboratory
      tests failed to identify which predicted the diagnostic utility of a laparotomy.
      Fifteen of the 53 IAC patients (28%) survived: 8 patients had had a therapeutic
      laparotomy, 1 patient underwent a nondiagnostic laparotomy, and 6 patients were
      managed nonoperatively. Multivariate analysis identified ventilator dependence (p
      = 0.004) and acute renal failure with creatinine level greater than 1.9 mg/dL (p
      = 0.011) as the most powerful predictors of mortality regardless of intervention.
      These data suggest a profile of cardiac surgical patients at risk for IAC as well
      as those patients who are most likely to benefit from timely intervention.

PMID- 7733724
TI  - Spontaneous recanalization of the esophagus after exclusion using nonabsorbable
      staples.
AB  - Perforations of the thoracic esophagus can be fatal unless diagnosed promptly and
      treated effectively. Two patients in whom primary repair was not feasible were
      treated by esophageal exclusion and diversion using nonabsorbable stapling
      devices. Both patients had spontaneous recanalization of the esophagus without
      leakage or stricture formation. We conclude that nonabsorbable staples can be
      used safely to achieve effective esophageal exclusion, thereby allowing complete
      healing of the perforation. Furthermore, use of this technique may eliminate the
      necessity for another major procedure to reestablish esophageal continuity.

PMID- 7733725
TI  - Diagnosis of infected modified Blalock-Taussig shunt by computed tomography.
AB  - Accurate localization of infection after pediatric cardiac operation is essential
      for correct decisions regarding treatment. We report a case of infection and
      endocarditis of a Blalock-Taussig shunt. Localization by computed tomography led
      to successful surgical intervention.

PMID- 7733726
TI  - Repeat replacement of aortic valve bioprosthesis.
AB  - We describe a safe and simple technique for replacing an aortic valve
      bioprosthesis in a patient who also had a previously implanted ascending aortic
      graft and multiple coronary artery bypass grafts. This method allows for isolated
      valve replacement without removal of the ascending aortic graft or alteration of
      the coronary artery bypass graft attachments.

PMID- 7733727
TI  - Neonatal pulmonary autograft implantation for cardiac tumor involving aortic
      valve.
AB  - We diagnosed in a 4-day-old neonate a cardiac tumor involving the left atrium,
      left atrioventricular junction, left ventricular outflow tract, and aortic valve
      with severe subvalvular and valvular aortic stenosis. The critical involvement of
      the aortic valve and the scarcity of neonatal cardiac donors led us to perform a
      successful replacement of the aortic root with a pulmonary autograft, using a
      very small homograft for the native pulmonary valve (Ross operation).

PMID- 7733728
TI  - Myxoma of the aortic valve.
AB  - Myxomas are one of the most common cardiac tumors but usually are confined to the
      atria. Although described in all cardiac chambers and on all cardiac valves, only
      one postmortem case of an aortic valve myxoma has been published. We present the
      case of a young man with an aortic valve myxoma with peripheral embolization. The
      other pathologic conditions with which valvular myxomas can be confused are
      compared and discussed.

PMID- 7733729
TI  - Right lower lobe herniation after domino heart-lung transplantation.
AB  - We report 2 cases of trapping and incarceration of the right lower lobe in the
      left hemithorax after heart-lung transplantation with bicaval anastamoses (domino
      donors). This occurred despite confirmation of the normal anatomy at the time of
      implantation, before lung inflation. In 1 case this complication resulted in a
      right lower lobectomy 7 days after transplantation due to infarction and
      infection of the right lower lobe. These cases illustrate the importance of
      reexamining the anatomy after lung inflation, before chest closure.

PMID- 7733730
TI  - Increasing cyanosis after total cavopulmonary connection treated by banding a
      separate liver vein.
AB  - An increasing right-to-left shunt after a total cavopulmonary connection was
      treated by banding the separate liver vein. As a variation on a fenestrated total
      cavopulmonary connection, this liver vein was not connected with the intercaval
      tunnel. After a few days, the shunt increased to an unacceptable level. This was
      treated by banding the liver vein, which was connected with the right-sided
      atrium and turned out to be only part of the venous drainage of the liver.

PMID- 7733731
TI  - Severe internal mammary artery atherosclerosis after correction of coarctation of
      the aorta.
AB  - Recently, we were unable to use the left internal mammary artery for coronary
      artery bypass grafting in 2 patients who had undergone successful late correction
      of coarctation of the aorta. In both patients, the mammary arteries were severely
      atherosclerotic and calcified; this may have resulted from prolonged and severe
      obstructive hypertension, which both patients had sustained before repair of the
      coarctation. Thus, in patients who have undergone late repair of coarctation, a
      bypass conduit other than the mammary artery may be needed.

PMID- 7733732
TI  - Circulatory support for myocardial infarction with ventricular arrhythmias.
AB  - Profound circulatory failure developed in a 45-year-old man after an acute
      myocardial infarction. A left ventricular assist device was used successfully to
      bridge the patient to transplantation despite recurrent and medically refractory
      ventricular arrhythmias that lasted from the second through the 12th day of
      circulatory support.

PMID- 7733733
TI  - "Thinning-down phenomenon" and vasomotor adaptability of the inferior epigastric
      artery graft.
AB  - We report a case of diffuse thinning of an inferior epigastric artery early after
      its implantation as a coronary free graft. This phenomenon showed reversibility
      at the 20-month angiographic follow-up in response to progression of the proximal
      lesion in the recipient coronary artery. Graft vasodilation in response to atrial
      pacing and nitroglycerin infusion at late angiography confirmed the vasomotor
      adaptability of this arterial conduit.

PMID- 7733734
TI  - Subclavian artery branch ligation reduces hemorrhage during resection of
      pulmonary aspergilloma.
AB  - Treatment of a 71-year-old woman with recurrent massive hemoptysis secondary to
      an aspergilloma and pleural aspergillosis is reported. Branches of the subclavian
      artery were ligated using an anterior approach before performing the thoracotomy,
      and pleuropneumonectomy was accomplished after ligation of the costal arteries.
      This technique provided a relatively bloodless field and minimized blood loss.

PMID- 7733735
TI  - Bronchogenic cyst of the right hemidiaphragm.
AB  - A rare case of bronchogenic cyst of the right hemidiaphragm is reported. The
      literature is reviewed briefly. Clinical presentation, diagnosis, and treatment
      of this entity are discussed further.

PMID- 7733736
TI  - Tricuspid valve prolapse associated with myxomatous degeneration.
AB  - Two surgical patients are presented with tricuspid valve prolapse. One had severe
      isolated prolapse of the posterior leaflet at its junction with the anterior
      leaflet accompanied by chordal elongation that was successfully repaired; the
      other had mild prolapse of all three leaflets with chordal elongation. Myxomatous
      degeneration of the tricuspid valve was the suspected underlying pathologic
      disorder in both patients and was histologically proven in the resected leaflet
      tissue of patient 1.

PMID- 7733737
TI  - Right atrial lipoma.
AB  - The case of a patient undergoing successful surgical resection of a huge lipoma
      of the right atrium is presented. The diagnosis was established preoperatively by
      magnetic resonance imaging. The tumor was involved intimately with the right
      coronary artery, and careful identification and dissection were required to
      preserve the vessel. The tumor was removed successfully, and follow-up at 1 year
      showed no evidence of recurrence.

PMID- 7733738
TI  - Massive hemothorax secondary to foreign body and CPR.

PMID- 7733739
TI  - Ultrasonic dissection: a useful adjunct to operation for calcified constrictive
      pericarditis.
AB  - We describe the use of an ultrasonic surgical dissector to remove calcified
      pericardium. This device proved to be useful for achieving safe and complete
      pericardial decortication in 2 patients.

PMID- 7733740
TI  - Technique for constructing the pulmonary trunk for tetralogy of Fallot with
      pulmonary atresia.
AB  - In expectation of the growth of a new pulmonary arterial trunk in total
      correction of tetralogy of Fallot with pulmonary atresia, we used pedicled
      autologous pericardium combined with left atrial appendage as the posterior wall
      of a new pulmonary arterial trunk. In cases of long discontinuity between the
      right ventricular infundibulum and left pulmonary artery, our technique could be
      recommended for early repair of tetralogy of Fallot with pulmonary atresia.

PMID- 7733741
TI  - A new device for exposing the circumflex coronary artery.
AB  - We have devised a new retractor for use in coronary artery bypass grafting that
      is made from three woven Teflon tapes. This method allows sufficient
      counterclockwise rotation of the heart, provides excellent exposure of the
      posterior and inferior coronary artery systems, and creates a horizontal surgical
      plane for the circumflex anastomosis.

PMID- 7733742
TI  - Tracheoesophageal fistula after blunt chest trauma.
AB  - Tracheoesophageal fistula is a very rare but potentially life-threatening
      complication of blunt chest trauma. Prior reviews have revealed that the victims
      were all young men involved in deceleration or crush injuries. Of those involved
      in motor vehicle accidents, most were thrown against the steering wheel. Herein,
      we review the world literature on this injury and include our own report of 1 of
      the few cases of traumatic tracheoesophageal fistula involving a female victim.
      In this case, the victim was an unrestrained driver thrown against an air bag.

PMID- 7733743
TI  - Update on mitral valve repair.

PMID- 7733744
TI  - 1988: The effect of glucose priming solutions in diabetic patients undergoing
      coronary artery bypass grafting. Updated in 1995.

PMID- 7733745
TI  - 1988: Continuous intercostal nerve block for pain relief after thoracotomy.
      Updated in 1995.

PMID- 7733746
TI  - Practice guidelines in cardiothoracic surgery. Valvular heart disease. Ad Hoc
      Committee for Cardiothoracic Surgical Practice Guidelines.

PMID- 7733747
TI  - Adjustable De Vega tricuspid valve annuloplasty guided by transesophageal
      echocardiography.

PMID- 7733748
TI  - De Vega annuloplasty: when to stop tightening the suture?

PMID- 7733749
TI  - Postpericardiotomy syndrome after pacemaker implantation.

PMID- 7733750
TI  - Effect of cardiopulmonary bypass on thyroid function.

PMID- 7733751
TI  - Ultrasound of inferior epigastric artery.

PMID- 7733752
TI  - Anomalous origin of the right gastroepiploic artery mistaken for graft occlusion.

PMID- 7733753
TI  - CNS Dysfunction after Cardiac Surgery: Defining the Problem. Proceedings of a
      conference on cardiopulmonary bypass. Fort Lauderdale, Florida, December 10-11,
      1994.

PMID- 7733754
TI  - Statement of consensus on assessment of neurobehavioral outcomes after cardiac
      surgery.

PMID- 7733755
TI  - Risk factors for cerebral injury and cardiac surgery.
AB  - Cerebral complications represent the leading cause of morbidity after cardiac
      operations. With the growing awareness of their social and economic importance,
      increasing attention is being given to their prevention. In the coronary artery
      bypass population, advanced age (> or = 75 years) is associated with an 8.9%
      neurologic deficit rate. Mortality is increased ninefold in the elderly patient
      with a neurologic deficit. Cardiopulmonary bypass has long been recognized as a
      cause of neuropsychologic deficits. Emboli are thought to be the causal agent.
      Retinal microvascular lesions during cardiopulmonary bypass as well as recent
      demonstration of widespread pathologic subcapillary arteriolar dilatations in the
      brain after cardiopulmonary bypass have been documented. Despite widespread
      interest in cerebral blood flow and neurologic deficits, there is no convincing
      evidence that defines a critically low or dangerously high level of flow. The
      ascending aorta represents a leading source of embolic neurologic injury. The use
      of intraoperative ultrasound to identify the diseased aorta may result in
      alternative operative strategies in an effort to minimize emboli and improve
      neurologic outcome. Existing literature offers conflicting views on optimal
      management of carotid artery stenosis in the coronary artery surgical patient. A
      trend that combined carotid endarterectomy and coronary artery bypass may often
      be appropriate will need confirmation through a multicenter clinical trial. Open
      cardiac surgical procedures, particularly in the aged population, carry a
      significant increased risk of adverse neurologic outcome. Postoperative
      arrhythmias may result in embolic neurologic deficit. A further understanding of
      risk factors for cerebral injury will be of value in developing therapeutic
      approaches to this major clinical problem.

PMID- 7733756
TI  - Macroemboli and microemboli during cardiopulmonary bypass.
AB  - Macroscopic and microscopic emboli of gas, biologic aggregates, and inorganic
      debris can occur during cardiac operations with cardiopulmonary bypass and may
      result in end-organ ischemia. In the current era pump-generated embolism is a
      diminishing cause of perioperative neurologic injury, which now appears to be
      related mostly to atheroembolism from manipulation of the atherosclerotic
      ascending aorta, and presents a continuing technical challenge to the surgeon.

PMID- 7733757
TI  - Brain microemboli associated with cardiopulmonary bypass: a histologic and
      magnetic resonance imaging study.
AB  - Emboli in brain tissue after cardiopulmonary bypass were reported in the
      literature 30 years ago, but there is little objective evidence confirming the
      presence of emboli in the brain after cardiopulmonary bypass with more modern
      equipment and techniques. Recently, with alkaline phosphatase vascular staining,
      we found an acellular fatty material in brain microvasculature from autopsy
      material of patients who died shortly after cardiopulmonary bypass. These fatty
      intravascular collections range in diameter from 10 to 70 microns, a size that
      lodges in the smallest vessels of the microvasculature. They have been found in
      numbers sufficient to cause detectable neurologic dysfunction and are believed,
      but not proved, to be emboli. By sequentially injecting colored microspheres, we
      can determine when emboli occur during experimental cardiopulmonary bypass. In
      ongoing related studies, magnetic resonance imaging was performed before cardiac
      valve replacement in 39 patients for whom preoperative and postoperative
      neurologic and neuropsychologic testing was available. Preliminary results
      suggest that magnetic resonance imaging evidence of prior stroke is not a
      significant risk factor for cognitive or motor decrement after cardiopulmonary
      bypass.

PMID- 7733758
TI  - The role of CPB management in neurobehavioral outcomes after cardiac surgery.
AB  - Recent developments in techniques for managing cardiopulmonary bypass are
      outlined with a view toward interventions aimed at decreasing the incidence of
      perioperative central nervous system dysfunction and overt stroke. Recent reports
      assessing central nervous system dysfunction after hypothermic and normothermic
      cardiopulmonary bypass are reviewed and critiqued along with data assessing
      techniques for cerebral protection during hypothermic circulatory arrest.
      Controversy surrounding optimal pH management is explored along with a proposal
      that pH-stat may be most satisfactory to ensure better brain cooling where
      circulatory arrest is anticipated, whereas alpha-stat may avoid cerebral
      hyperemia and thus decrease the cerebral embolic load during moderate hypothermic
      cardiopulmonary bypass. Newer developments in cerebral monitoring techniques are
      also reviewed.

PMID- 7733759
TI  - Signs of brain cell injury during open heart operations: past and present.
AB  - Signs of brain cell injury have been studied during the evolution of open heart
      surgery in the last quarter century. At the beginning of the period, it was
      possible to elucidate signs of brain injury with rather crude psychometric tests
      and clinical observations in seemingly normal patients having routine operations.
      Over the next 5 years, a marked improvement in psychometric scores was observed.
      However, a biochemical cerebral cell injury marker (adenylate kinase) showed
      increased levels in the cerebrospinal fluid, a finding indicative of brain cell
      injury. There was a correlation between cerebrospinal fluid levels of adenylate
      kinase and psychometric test results as well as between the marker levels and
      clinical signs. Because of the relative insensitivity of the psychometric tests
      used and the increasing difficulty in receiving permission for spinal fluid taps,
      other methods were sought. Refined psychometric memory tests were used and showed
      that even in the 1990s, there are subtle signs of brain cell injury during open
      heart operations. This finding was corroborated by using a highly brain-specific
      and brain-sensitive biochemical cell injury marker (S-100 beta) that increased
      during extracorporeal circulation and showed a correlation with clinical cerebral
      complications.

PMID- 7733760
TI  - Glutamate, calcium, and free radicals as mediators of ischemic brain damage.
AB  - Calcium is considered a mediator of ischemic brain damage whether this is due to
      global or forebrain ischemia or to focal ischemia. Supporting evidence is the
      translocation of extracellular calcium into cells during ischemia, the
      precipitous rise in the free cytosolic calcium concentration, and the role of
      calcium in activating lipases, proteases, kinases, phosphatases, and
      endonucleases in potentially harmful metabolic cascades. In vitro and in vivo
      experiments suggest that the main route of entry is through channels gated by
      glutamate receptors. These experiments led to the excitotoxic hypothesis of cell
      death. The in vitro experiments further support the role of calcium as a mediator
      of cell death. Both cell calcium overload and acidosis enhance the production of
      partially reduced oxygen species, thus predisposing to free radical-related
      damage. In transient global or forebrain ischemia, free radicals formed during
      reperfusion may contribute to a perturbed membrane function, leading to a
      sustained alteration of cell calcium metabolism with ultimate mitochondrial
      calcium overload. In focal ischemia (stroke), free radicals may be important
      mediators of the infarction process. Infarction can be regarded as a form of
      secondary damage, which is probably caused by microvascular dysfunction. Very
      likely, such dysfunction is triggered by upregulation of adhesion molecules such
      as ICAM-1, microvascular "plugging," and an inflammatory response at the blood
      endothelial cell interface. The involvement of free radicals in this type of
      secondary damage is supported by results showing that nitrones that act as free
      radical spin-traps ameliorate focal ischemic damage with a therapeutic window of
      many hours.

PMID- 7733761
TI  - Cerebral hemodynamics after low-flow versus no-flow procedures.
AB  - Temperature induces depression of cerebral perfusion and cerebral oxygen
      metabolism in particular, and this seems to explain why a reduced pump flow above
      a critical level is well tolerated during hypothermic cardiopulmonary bypass with
      apparent full metabolic recovery afterward. It only partly explains why a longer
      period of hypothermic circulatory arrest leads to a protracted recovery of
      cerebral perfusion and cerebral metabolism. This review suggests there is
      evidence that energy metabolism can easily be compromised during and after
      rewarming after hypothermic cardiopulmonary bypass with low flow and with
      circulatory arrest. Although data indicate that cerebral metabolism and cerebral
      energy state are better after low flow than after circulatory arrest, the risk of
      energy crises appears imminent with both techniques.

PMID- 7733762
TI  - Predictors of cognitive decline after cardiac operation.
AB  - Despite major advances in cardiopulmonary bypass technology, surgical techniques,
      and anesthesia management, central nervous system complications remain a common
      problem after cardiopulmonary bypass. The etiology of neuropsychologic
      dysfunction after cardiopulmonary bypass remains unresolved and is probably
      multifactorial. Demographic predictors of cognitive decline include age and years
      of education; perioperative factors including number of cerebral emboli,
      temperature, mean arterial pressure, and jugular bulb oxygen saturation have
      varying predictive power. Recent data suggest a genetic predisposition for
      cognitive decline after cardiac surgery in patients possessing the apolipoprotein
      E epsilon-4 allele, known to be associated with late-onset and sporadic forms of
      Alzheimer's disease. Predicting patients at risk for cognitive decline allows the
      possibility of many important interventions. Predictive power and weapons to
      reduce cellular injury associated with neurologic insults lend hope of a future
      ability to markedly decrease the impact of cardiopulmonary bypass on short-term
      and long-term neurologic, cognitive, and quality-of-life outcomes.

PMID- 7733763
TI  - Cardiopulmonary bypass: perioperative cerebral blood flow and postoperative
      cognitive deficit.
AB  - Increased cerebral blood flow occurring during cardiopulmonary bypass as a result
      of changes in arterial carbon dioxide tension during acid-base regulation is
      thought to increase postoperative cognitive dysfunction. We studied 70 patients
      undergoing coronary artery bypass procedures who were randomized to two different
      acid-base protocols: pH-stat or alpha-stat regulation. Cerebral blood flow,
      cerebral blood flow velocity, and cerebral oxygen metabolism were measured before
      bypass, during bypass (hypothermic [28 degrees C] and normothermic phases), and
      after bypass. Detailed cognitive tests were conducted before operation and 6
      weeks after operation. During 28 degrees C bypass, cerebral blood flow was
      significantly (p < 0.05) higher in the pH-stat group than in the alpha-stat group
      (41 +/- 2 versus 24 +/- 2 mL.100 g-1.min-1), and cerebral blood flow velocity was
      significantly increased in the pH-stat group and significantly decreased in the
      alpha-stat group (152% +/- 10% versus 78% +/- 7%). Cerebral extraction ratio of
      oxygen demonstrated a relatively greater disruption of autoregulation in the pH
      stat group than in the alpha-stat group with relative hyperemia of 0.12 +/- 0.02
      versus 0.26 +/- 0.03, respectively, during 28 degrees C bypass. Using the
      criterion of deterioration in three or more neuropsychologic tests, a
      significantly higher proportion of patients in the pH-stat group fared less well
      than in the alpha-stat group (49% +/- 17% versus 20% +/- 13%). Patients in the
      alpha-stat group experienced less disruption of cerebral autoregulation during
      hypothermic cardiopulmonary bypass, and this was accompanied by a reduction in
      postoperative cognitive dysfunction.

PMID- 7733764
TI  - Long-term neurologic outcome after cardiac operation.
AB  - Cardiac surgical patients face the threat of neurologic complications in all
      phases of their disease and its treatment. The incidence of preoperative
      transient ischemic attacks and stroke ranges from 5% to 14% and from 2% to 11%,
      respectively. The risk of preoperative cerebrovascular accidents is higher in
      patients with valvular disease than in those with coronary artery disease. The
      prevalence of postoperative neurologic disorders varies widely because of
      differences in defining the clinical criteria, heterogeneity of patient
      populations, timing of evaluation, follow-up times, study designs, and surgical
      and anesthesia-related procedures. Fatal cerebral damage is very rare (< 0.1%).
      Focal cerebral deficits, or definite stroke, are encountered in 1% to 3% of
      patients and minor clinical abnormalities, in 5% to 10%. Recent studies have
      shown that contrary to previous concepts, valve replacement does not carry
      essentially higher neurologic risks than coronary bypass grafting. The most
      common causes of operation-related neurologic disorders are microembolization or
      macroembolization and hypoperfusion. Although most disorders resolve early
      postoperatively, some deficits persist. From the neurologic standpoint, a main
      objective of a cardiac surgical intervention is to prevent stroke. Today, the
      incidence of cardiogenic cerebrovascular accidents is very low after reparative
      cardiac procedures. Despite surgical and anesthesia-related improvements,
      neurologic complications do occur. Multidimensional investigatory procedures have
      shown that cardiopulmonary bypass often causes cerebral dysfunction. Whether the
      harmful consequences are detected depends on the evaluation criteria and the
      investigatory methods and timing used. Further methods are needed to prevent or
      treat preoperative cerebrovascular accidents and particularly to improve cerebral
      protection during operative procedures.

PMID- 7733765
TI  - Selection and clinical significance of neuropsychologic tests.
AB  - There have been major advancements in cardiac surgery over the past two decades
      and a concomitant decrease in mortality and major morbidity. The improved safety
      in cardiac procedures permitted 330,000 operations involving cardiopulmonary
      bypass in 1992. However, several recent studies have demonstrated that cardiac
      surgery poses substantial risk of negative neurologic and neuropsychologic
      outcomes. Although very few patients die as a result of a cardiac operation, more
      than two thirds of patients demonstrate evidence of neuropsychologic dysfunction
      postoperatively. The mechanisms contributing to neuropsychologic deficits after
      cardiopulmonary by-pass are uncertain. To characterize the incidence and severity
      of such deficits after cardiac operations, a concise battery of neuropsychologic
      tests that provides reliable evidence of subtle brain trauma is essential. With
      an objective, valid measure of brain injury, the etiology of neuropsychologic
      deficits can be identified and either eliminated or the effects ameliorated. The
      proper selection and use of neurobehavioral tools provides a basis to evaluate
      the efficacy of surgical and pharmacologic interventions to further improve
      neurologic outcome after cardiopulmonary bypass.

PMID- 7733766
TI  - Methodological issues in the assessment of neuropsychologic function after
      cardiac surgery.
AB  - This report reviews critical issues facing investigators interested in
      neuropsychologic sequelae after cardiac operations: (1) experimental design; (2)
      selective attrition; (3) selection of instruments; (4) moderating factors; (5)
      definitions of cognitive decline; (6) statistical analysis; and (7) clinical
      significance. Implications for further research in the area are discussed.

PMID- 7733767
TI  - Analysis and interpretation of neuropsychologic tests in cardiac surgery.
AB  - Neuropsychologic assessment in the context of cardiac surgery is constrained by
      the clinical time available to see patients, and as such test selection needs to
      be carefully planned. Besides the time limitations, it differs from clinical
      neuropsychologic assessment primarily because it tends to involve at least two
      assessments, a comparison with performance before operation, and a limited number
      of tests. The analysis and design issues involved in both incidence studies and
      intervention studies are discussed in this article. Incidence studies customarily
      involve a single group assessed on at least two occasions and are designed to
      identify the numbers of individuals who show clear evidence of neuropsychologic
      changes after a cardiac operation. Intervention studies involve at least two
      groups where one factor (eg, surgical equipment) is varied systematically. The
      research on neuropsychologic deficits after cardiac operations has progressed
      from incidence studies, which involve a conventional definition of deficit, to
      intervention studies, in which specific test performance can be compared.

PMID- 7733768
TI  - Neurologic complications of coronary artery bypass grafting: diffuse or focal
      ischemia?
AB  - The central nervous system complications arising during or shortly after coronary
      artery bypass grafting are due to cerebral ischemia associated with hypotension
      and to embolism. Hemodynamic compromise produces a spectrum of disturbance of
      consciousness and mentation ranging from brain death and coma through the chronic
      vegetative state to mild confusion. Watershed infarction may add to this picture
      focal deficits such as visual disorientation and cortical field defects or
      bibrachial weakness (the "man in a barrel" syndrome). Macroembolism accounts for
      most perioperative strokes and is related to cardiac arrhythmias, to intracardiac
      thrombus, and particularly to the severity and friable nature of any aortic
      atheroma. Microembolism can cause focal problems in the watershed territory but
      is normally responsible for diffuse changes as seen in the neuropsychologic
      sequelae of coronary artery bypass grafting. Coexistent carotid artery disease
      rarely contributes to the postoperative neurologic changes.

PMID- 7733769
TI  - Cerebral dysfunction after cardiac surgery: closing address.

PMID- 7733770
TI  - [Comparative in vitro activity ampicillin, cefoperazone, their combinations with
      sulbactam, as well as that of other antibiotics against aerobic gram-negative
      microorganisms].
AB  - The activity of 12 antibiotics against 849 strains of gram-negative aerobes
      isolated in special and general hospitals of Moscow and Smolensk in 1992-1993 was
      assayed with the method of serial microdilutions. By the criteria of the activity
      (percentage of the susceptible strains by the NSSLS criteria) against the
      isolates the antibiotics were arranged as follows: ciprofloxacin (89.8 per cent)
      > imipenem (89.6 per cent) > cefoperazone + sulbactam (86.1 per cent) > amikacin
      (83.8 per cent) > ceftazidime (81.8 per cent) > ceftriaxone (71.1 per cent) >
      cefoperazone (70.9 per cent) > cefotaxime (70.9 per cent) > gentamicin (60.8 per
      cent) > ampicillin + sulbactam (44.7 per cent) > cefazolin (37.5 per cent) >
      ampicillin (23.0 per cent). The frequency of the antibiotic susceptible isolates
      in the special hospitals was lower at the average by 20 per cent than that in the
      general hospitals with respect to all the antibiotics assayed.

PMID- 7733771
TI  - [Effect of calcium ions on the differentiation of actinomycetes].
AB  - The influence of Ca2+ on the formation of the aerial mycelium in 23 actinomycete
      strains was studied. It was shown that in concentrations up to 5 mM exogenous
      Ca2+ induced the formation of the aerial mycelium in 11 out of the 23
      actinomycete strains tested. The Ca2+ channel blockers (verapamil and
      nifedipine), calmodulin inhibitor (chlorpromazine) and Ca2+ chelator (EGTA)
      inhibited the aerial mycelium formation in 3 streptomycete strains out of the 23
      actinomycetes. Chlorpromazine and nifedipine proved to be the most active
      inhibitors when used in concentrations of 0.2 to 2.5 mumol/disk. The Ca2+
      concentrations of 5 mM were found to stimulate the formation of the submerged
      spores in S. hygroscopicus 155. The activity of ATP synthase was stimulated in
      the aerial and submerged spores after the Ca2+ uptake.

PMID- 7733772
TI  - [Additional differentiation of methicillin resistant strains of Staphylococcus
      aureus typed by the international phage bank].
AB  - In the methicillin resistant strains of Staphylococcus aureus (MRSA) typed by the
      International Set phages the host specificity of the restriction-modification of
      the phage 85 DNA was determined, the finger printing of the cell DNA was carried
      out with using two probes and the lytic spectrum of the phages induced in them
      was studied. Four clones with different specificity of the restriction
      modification system (rm89, rm108, rm121 and rm947) differing from that of strain
      PS 85 which is the host of phage 85 were detected. The strains belonging to the
      modification types m89, m108 and m121 contained prophages (within the respective
      groups) with similar lytic spectra when tested with the use of the PS strains of
      the International Collection and had cross antiphage immunity. Six phage variants
      were detected among the phages induced in the strains with the modification type
      m947 which could be indicative of the clone heterogeneity.

PMID- 7733773
TI  - [Metabolic transformation of antibiotics of the tetracycline series in peroxidase
      reactions].
AB  - In was shown calorimetrically that in the presence of horse radish peroxidase
      tetracyclines induced degradation of hydrogen peroxide. Under such conditions
      changes in the tetracycline optical properties were detected photometrically. It
      was concluded that tetracyclines were metabolized in the peroxidase reactions
      catalyzed by horse radish peroxidase as their substrates. The tetracycline
      peroxidase oxidation was catalyzed not only by horse radish peroxidase but also
      by methemoglobin possessing the peroxidase activity. In the experiments with
      ascorbate there were detected characteristic peculiarities of the tetracycline
      peroxidase oxidation catalyzed by both horse radish peroxidase and methemoglobin.
      These peculiarities made it possible to classify the tetracyclines as the
      substrates of the peroxidase reaction belonging to the oxidogenic group. The fact
      that tetracyclines can be metabolized in peroxidase reactions is discussed in
      regard to its possible influence on their mechanism of antibacterial action and
      the development of tetracycline resistance.

PMID- 7733774
TI  - [Automated systems and computer programs in microbiologic practice].

PMID- 7733775
TI  - [Synergistic action of recombinant preparations of gamma-interferon and tumor
      necrosis factor on the course of experimental staphylococcal infection].
AB  - The action of recombinant gamma-interferon (rINF-gamma) and tumor necrosis factor
      (rTNF-alpha) as well as that of their combinations was studied in a model of
      staphylococcal infection. It was observed that the use of rINF-gamma alone was
      not sufficient for the activation of the effector antibacterial function of
      macrophages with respect to staphylococci. At the same time it was shown that
      rTNF-alpha and rINF-gamma had a synergistic action on the process of the
      infection in mice evident from an increase in the pathogen elimination in the
      host. The use of the combination in the optimal doses increased the bactericidal
      activity of macrophages in the infected animals.

PMID- 7733776
TI  - [Characterization of microflora in pyo-destructive lung diseases].
AB  - The microflora pattern of the endobronchial secretion was investigated in 74
      patients with purulent destructive diseases of the lungs. Specimens of the
      endobronchial secretion were collected by transtracheal aspiration and
      bronchoalveolar lavage. The anaerobic isolates were cultivated in anaerostats
      (OXOID, England) with the use of GasPacks. Bacteriological identification of the
      pathogens was carried out with respect to 67 patients (90.5 per cent). Non
      sporulating anaerobic microflora was isolated from 51 patients (76.1 per cent).
      Anaerobic causative agents in the patients with complicated pulmonary
      destructions were detected in 54.3 per cent of the cases. Mono-infection
      represented by one species of the anaerobes was stated in 23 patients (34.4 per
      cent). Associations of aerobes and anaerobes were isolated from 28 patients (41.7
      per cent). Associations of one strain of the anaerobic causative agents and
      aerobic microflora were detected in 17 patients (60.7 per cent). In 11 patients
      the microflora pattern was polymicrobial (89.3 per cent). A total of 66 strains
      of non-sporulating anaerobic pathogens were isolated. Gram-negative bacilli
      represented by Prevotella spp., Porphiromonas asaccharolitica and Bacteroides
      spp. were the most frequent isolates.

PMID- 7733777
TI  - [Microbiological basis for organization of rational use of antibiotics in
      surgery].

PMID- 7733778
TI  - [Deep mycoses].
AB  - The problems of the diagnosis of deep mycoses such as candidiasis, aspergillosis
      and actinomycosis most frequent in this country are discussed. A classification
      system for deep mycoses based on the characteristics of the causative agents
      which is of practical value is presented. The microscopic and cultural
      diagnosticating of deep mycoses is described in detail. A brief information on
      the principles of the treatment of the mycoses is given.

PMID- 7733779
TI  - [Ninth international symposium on the biology of actinomycetes].

PMID- 7733780
TI  - [Analysis of higher fatty acids of fungi of the genus Candida using gas
      chromatography].
AB  - The fatty acid composition of the cell biomass of 136 strains of 9 species
      belonging to the genus Candida was investigated. The cell walls were found to
      contain the following fatty acids: myristic, hexadecenoic, palmitic,
      heptadecanoic, linoleic, linolenic, stearic, lignocerinic and oleic. Acids with
      18 carbon atoms in the chain i.e. oleic, linoleic and linolenic predominated.
      Every species had a special ratio of the acids. In the taxonomic determination of
      fungi within Candida as well as other yeast-like fungi it was shown promising to
      consider the composition of the higher fatty acids in the cells.

PMID- 7733781
TI  - [Antibiotic resistance of Campylobacter strains and its role in evolutionary
      processes in bacteria of the genus Campylobacter].
AB  - The influence of multiple antibiotic resistance of Campylobacter strains
      determined by R plasmids on their virulence was studied. It was shown that the
      strains with multiple resistance were mostly isolated from children with
      campylobacteriosis (26.5 per cent). The number of such strains isolated from the
      infected adults, hens and environmental objects amounted to 25.8, 23.3 and 21.4
      per cent respectively. The difference of the resistance determinants in the
      tested strains was statistically insignificant. It was suggested that the R
      plasmids of the human strains could be as well detected in the strains from the
      infected hens and environmental objects. A chromosome-plasmid pattern of the
      Campylobacter resistance to kanamycin, tetracycline and erythromycin was
      determined. The analysis of the cytopathogenic activity of the plasmid-containing
      strains and their aplasmid clones revealed that this criterion of the virulence
      statistically significantly increased after the plasmid loss by the strains. It
      was concluded that the antibiotic resistant strains had a selective superiority
      while circulating in various ecological niches.

PMID- 7733782
TI  - [Preclinical pharmacokinetics of pefloxacin].
AB  - The substance and tablets of pefloxacin mesilate manufactured by the Urals
      Polytechnical University and the National Research Centre of Antibiotics were
      studied on rats and dogs with the drug oral administration in single and multiple
      doses equivalent to the human ones. The bioavailability of the drug was good and
      its blood levels were efficient for a prolonged period (at least 24 hours) after
      a single oral administration. No cumulation of the antibiotic after its repeated
      use was observed. The pefloxacin mesilate tablets proved to be fully equivalent
      to the drug manufactured by Rhone-Poulenc-Rorer (France).

PMID- 7733783
TI  - [Chemotherapeutic effectiveness of pefloxacin in experimental infections].
AB  - High efficacy of pefloxacin was shown in its study on albino mice with
      experimental infections such as sepsis, pneumonia and peritonitis. In the
      effective doses administered orally the drug rapidly arrested the clinical signs
      of the diseases and provided the sanation of the organs and tissues. The broad
      antibacterial spectrum of pefloxacin substantiated its efficacy in the treatment
      of purulent septic processes due to gram-negative and gram-positive pathogens, as
      well as in the treatment of mixed infections. It is a drug with prolonged action
      which was confirmed with its prophylactic use. Pefloxacin was efficient in the
      treatment of infections of various severity.

PMID- 7733784
TI  - [Stability of various cephalosporins in solutions. Cefazolin, cefazedone,
      cefaclor].
AB  - The kinetics of splitting out the substitute at C3 in the molecule of beta-lactam
      antibiotics such as cefazolin, cefaclor, cefazedone and others as well as that of
      splitting out the chlorine atom in the side radical of the cefazedone molecule
      was studied within wide ranges of pH and temperature. The destruction processes
      for all the investigated compounds were shown to be described by the 1st order
      equations. The values of the activation energy, pre-exponential factors and
      reaction order by the hydrogen ions were measured. This provided the mathematical
      description of the destruction processes within wide ranges of pH and
      temperature. An unusual mechanism of synchronous splitting out the substitute at
      C3 and one of the chlorine atoms in the side radical of the cefazedone molecule
      was observed.

PMID- 7733785
TI  - [Use of a combination of cefoperazone with sulbactam for treatment of patients
      with wound infections].
AB  - The clinical efficacy of sulperazone (cefoperazone + sulbactam) manufactured by
      Pfizer (USA) was studied in the treatment of 25 patients with wound infections.
      By the disease severity and complications 9 patients belonged to the risk group.
      Insulators with abacterial media or bandages with ointments on the polyethylene
      glycol base and drugs stimulating reparative processes (methyl-diadioxylin,
      dioxyzol, gentacycol) were used for the local treatment of the wounds. The
      clinical efficacy was stated in 92 per cent of the cases and in 76 per cent of
      the cases the efficacy was bacteriological. The tolerance of sulperazon was good
      in all the cases. The signs of the drug intolerance or affection of the hepatic
      or renal function were not detected. 281 clinical isolates of the aerobic
      microflora were tested for their antibiotic susceptibility. The highest
      susceptibility to sulperazone was observed in gram-positive organisms, gram
      negative bacilli (Proteus mirabilis, Escherichia coli and Klebsiella spp.) and
      some nonfermenting bacteria.

PMID- 7733786
TI  - [Cefodizime--a new 3rd generation cephalosporin antibiotic for parenteral use].

PMID- 7733787
TI  - [Microturbidimetric method for determining the activity of polymyxin M].
AB  - A microturbidimetric procedure for the assay of polymyxin M activity was
      developed. The assay is performed in polystyrene 96-well plates usually used for
      immunological tests.

PMID- 7733788
TI  - [Effect of a diet supplemented with soybean oil or fish oil on the reversibility
      of docosahexaenoic acid deficiency (22:6w3) in the brain and erythrocytes of
      rats].
AB  - This study was undertaken, to evaluate the effects of dietary supplements
      containing either soybean oil (19:3w3; ALA), or fish oil (22:6w3; DHA), added to
      the lactating rat dam diet, on the levels of DHA in brain and erythrocytes of DHA
      deficient pups. Pregnant rats fed omega 3 deficient diets were divided at
      parturition into three groups. One group was kept on the same diet fed during
      pregnancy. The two remaining groups received the above mentioned omega 3
      supplements. These feeding regimens were maintained during 18 days.
      Supplementation of diet with 114 mg DHA/100g diet, increased significantly the
      concentration of DHA in brain and erythrocytes of the suckling rats. In contrast,
      the effects of the supplementation with ALA (700 mg/100g diet), were limited to
      the increase of DHA content in the brain. This increase however, was partial,
      reaching only 50% of the normal. Results suggest that newborn rat has a limited
      capacity to convert DHA from ALA, becoming dependent of preformed DHA supply to
      cover DHA requirements at the cellular level.

PMID- 7733789
TI  - [Behavior of iron fixed on bovine and phosphorylated casein after hydrolysis
      produced by digestive proteases].
AB  - The phosphate groups of the native and phosphorylated casein have the property of
      sequestering the iron. This metal fixation depends on the casein's degree of
      phosphorylation. The phosphate groups either, naturally present or chemically
      binded, are the preferential fixation sites for iron. They modify the affinity
      constant of the casein respecto to iron. Both, phosphorylation and ironfixation
      influence negatibily the caseins sensibility to digestive protease. Whichever the
      enzyme might be, the hydrolysis of the casein with fixed iron produces fixed iron
      peptides. It seems that iron retention is a function of the number of phosphate
      groups associated to casein.

PMID- 7733790
TI  - [Osmotic dehydration of apple (Grany Smith) with different osmotic solutions].
AB  - The process of osmotic dehydration in apple rings at 40 degrees, 50 degrees and
      60 degrees C in two osmotic agents were studied. The agents were similar in
      concentration, water activity and viscosity but differed in composition. The
      weight loss, water content, solids uptake and Brix showed differences in the
      medius studied. In syrup corn medium, the weight loss was higher and the solids
      uptake was lower than syrup sucrose. The polysacharides from the syrup corn
      lowered solutes uptake and the water out was facilited.

PMID- 7733791
TI  - [Substitution of wheat flour by defatted palm meal flour, rich source of dietetic
      fiber in the preparation of cookies and breads].
AB  - A flour from defatted oil palm kernels was used for substitution of wheat bran
      for the preparation of dietary fiber-rich wheat cookies and bread. The flour,
      containing 71% insoluble dietary fiber, 2% soluble dietary fiber and 19% protein
      (dry basis), was used at three different levels (3%, 4.5% or 6%) for the
      formulation of cookies, and at 2.5% and 5% for the preparation of bread.
      Commercial samples containing 6% and 5% wheat bran for the cookies and bread,
      respectively, were used as reference products. The dietary fiber content ranged
      between 6.8 and 10.1% for the experimental cookies and between 5.1 and 7% for the
      corresponding breads. Both types of products showed lower starch content (42-50%
      for cookies and 34-36% for breads) than the reference samples. Protein quality,
      as assessed by true and apparent digestibility, PER and NPR, was similar for
      experimental and reference cookies and breads. The final product texture
      (increased/decreased) as dietary fiber level increased. Flavor tests performed
      with both an untrained panel and the cookie senior chef indicated preference for
      the 3% palm flour cookies and the 2.5% flour bread. No change in pH regulating
      compounds was observed in either experimental or reference cookies, although a
      slight increase in humidity was recorded for the palm flour-based cookies. The
      experimental bread whiteness decreased as the palm flour level
      increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7733792
TI  - Fortification of precooked maize flour with coarse defatted maize germ.
AB  - The possibility of improving the dietary value of precooked maize flour through
      fortification with 11% coarse defatted maize germ was investigated. The results
      of tests in humans presented here show that the total iron absorption from the
      fortified preparation is similar to that from the precooked maize alone, but with
      the advantage of being richer in several nutrients: protein (25%), zinc (61%),
      potassium (47%) and magnesium (112%), as well as fiber (34%). Fortification
      lowers (by 20%) rather than raises the cost of the flour, and may be an important
      contribution to the diet of those populations where maize bread is a major
      component of the diet.

PMID- 7733793
TI  - [Declaration of Quito for the universal salt iodination].

PMID- 7733794
TI  - [Werner G. Jaffe. Eighty years of exemplary life].

PMID- 7733795
TI  - Dietary fibre, what it is and how it is measured.
AB  - Carbohydrates are the major component of the human diet and are an important
      source of energy. The World Health Organization recommends that 50-70% of
      ingested carbohydrates should be in the form of polysaccharides such as starch. A
      small proportion of dietary carbohydrate is in the form of non-starch
      polysaccharides (NSP) (Dietary Fibre). Dietary Fibre is a medically important
      component of the diet since epidemiological evidence links it with the etiology
      of various diseases. Scientists have engaged in trying to understand the
      mechanism by which dietary fibre prevents disease. This article highlights the
      lack of consensus on its chemical definition and the advantages and disadvantages
      of the two main methods used to measure it. These are the enzymic gravimetric
      method (AOAC) that measure fibre as the weight of residual matter following
      enzymic treatment of the food; and the enzymic chemical method that identifies
      and measures fibre from its chemical components. The latter method, proposed by
      Englyst and Cummings measures dietary fibre as NSP and gives detailed information
      about its components. This is important for interpreting epidemiological and
      physiological studies. The precise and confident measure of the different
      components of carbohydrates is important in Latin America. It will allow a
      coherent, scientific and rational approach to the role of carbohydrates in
      health.

PMID- 7733796
TI  - [Dietary fiber and gastro-intestinal tumors, implications for the Mexican
      population].
AB  - Certain nutrients serve as individual influences in the development or protection
      against chronic and/or degenerative diseases. Specifically, it has been observed
      that the abundant consumption of dietetic fiber is a protective factor against
      tumors of the digestive system. Many scientific articles have reported mechanisms
      by which dietetic fibers exert an important protective effect for colon cancer
      and in lesser degree against cancer of the stomach and rectum. In Mexico during
      1990, neoplasms were the second cause of general mortality for the persons over
      the age of 65 years. The Fourth National Report of Cancer in Mexico revealed that
      tumors of the digestive tube were the third most frequent type of neoplasm in the
      country and that stomach cancer had the greatest incidence among cancers which
      affect this system. To date, we do not know how much the urban immigration and
      the consequent changes in food patterns have acted as cofactors for the increase
      in this type of tumors. During the seventies, a number of national and regional
      nutritional surveys showed that the Mexican population had a high consumption of
      fiber, as part of the traditional diet, comprised primarily of tortilla and
      beans. At the present time, the national dietary patterns have changed; the
      increasing consumption of high energy foods with a low nutritional value is
      associated with much less ingestion of dietary fiber. This article points out
      that the population may have additional digestive cancer risks, due to new food
      consumption patterns which have reduced the availability of dietary fiber.

PMID- 7733797
TI  - [Endemic goiter in three census areas of Chile].
AB  - The goal of the present study was to evaluate the current status of endemic
      goiter in Chile. 3500 students of basic education from public schools in three
      censor areas of the country were studied: 1000 in Calam (North), 1000 in Temuco
      (South) and 1500 in Santiago (Center). Socio-economic level was evaluated
      according to the Graffar scale. Two trained physicians determined body weight,
      height and size of the goiter through palpation of the thyroid gland (according
      to W.H.O. classification). Iodine in urine was determined in 20% of the students.
      Iodine insalt was determined in samples obtained in the three areas. A goiter
      prevalence of goiter of 11.4% in males and 12% in females was found, with a
      higher prevalence in females during puberty. A higher prevalence in the medium
      low and low socio-economical levels was observed (12.4% and 14.4% respectively).
      The level of salt iodination was variable in the three areas (1/3 with
      concentration > than 100 parts per million (ppm), 1/3 between 60-100 ppm and 1/3
      with < 60 ppm of iodine content). According to W.H.O. criteria, Chile has
      presently a low goiter prevalence, but the salt iodine concentration indicate the
      importance of a permanent surveillance of iodine nutrition.

PMID- 7733798
TI  - [Evolution of child undernutrition in Chile and some of its conditioning factors:
      a time series analysis].
AB  - The objective of this study was to determine the evolution of the nutritional
      status of the population under five years of age during the period 1975-1990.
      Several conditioning factors were also assessed. The information was evaluated
      through time series analysis by using the AREG procedure. This procedure allows
      for the estimation of a regression model correcting by the autocorrelation of
      errors. Results indicates a significant trend to decreased undernutrition rates
      (p < 0.0001). A seasonal effect on undernutrition was observed, being higher the
      prevalences in summer. Analysis of selected conditioning factors, as well as the
      familiar buying capacity remained stable during the period. An exception to the
      lack of association among undernutrition and the conditioning factors evaluated,
      was seen during the period 1975-1982 when clear inverse relationship was
      evidenced. In conclusion, the decrease of infant undernutrition in Chile during
      the period 1975-1990 was not related to the changes observed in certain
      socioeconomic indices.

PMID- 7733799
TI  - Dietary fish oil affects food intake, growth and hematologic values of weanling
      rats.
AB  - The object of this study was to evaluate the effect of increasing amounts of
      dietary fish oil on growth and hematological variables of the weanling male
      Sprague-Dawley rat. Animals were fed diets containing either fish oil (FO) or
      sesame oil (SO) at 5, 10 or 15% (w/w) for 31 d. Growth retardation and reduced
      food intake was noted in groups fed FO. Hemoglobin (Hb) concentration diminished
      when the dietary FO was above 5% (w/w). FO is a poor source of (n-6) fatty acids.
      We postulate that a partial deficiency in (n-6) polyenic family, is a consequence
      of the increasing amounts of FO in the diets, that may affect growth and
      erytropoiesis. In this report we show evidence supporting the hypothesis that
      diets enriched with fish oil can alter normal growth and induced hematological
      changes in the male weanling rat.

PMID- 7733800
TI  - [Effect of food consumption restriction in adult rats on the growth and tissue
      composition of their suckling offspring].
AB  - The repercussion of food restriction consumed by the adult rat during pregnancy
      and lactation, on the postnatal growth and tissue composition of the young was
      evaluated during lactation. Two groups of Sprague-Dawley rats were used, one
      control group was fed "ad libitum" (AL) and the other group, a restricted diet
      (RD), 30% less of the normal diet. From the eight day of pregnancy and throughout
      lactation, the food intake and weight of the animals was registered daily. At
      birth the number of young was adjusted to eight and the weight and tail length
      were registered daily. At 7, 14, and 21 days of lactation the young of both
      groups were sacrificed. The liver and the muscles of the extreme posterior were
      dissected and the wet weight, dry weight, proteins and nucleic acids determined.
      The mother rats fed "ad libitum increase their intake to 300% from the first day
      of lactation and they presented a greater body weight than those rats under
      restricted diet, also begun on the first day of lactation. At birth there were no
      differences in the weight and the length of the young, however at the end of the
      lactation the growth rate was significantly lower among the group of rats RD. In
      the group of young under RD, protein and nucleic acids concentration in the liver
      were significantly less than those of the AL group and similarly in the muscle,
      the dry weight, proteins, RNA and DNA were significatively less. From these
      results it is concluded that the food restriction of the adult rat by 30% during
      lactation, has a negative effect on the postnatal growth of the young, in terms
      of weight, length, liver tissue composition and muscular mass.

PMID- 7733801
TI  - Differences between heterosexual, bisexual, and lesbian women in recalled
      childhood experiences.
AB  - Heterosexual, bisexual, and lesbian women recalled the extent to which they had
      engaged in gender conforming (female-stereotypic) behaviors and gender
      nonconforming (male-stereotypic) behaviors in childhood. Heterosexual women were
      more likely to recall having had female-stereotypic experiences as children,
      whereas lesbian women often recalled a childhood characterized by male
      stereotypic experiences. Multiple discriminant function allowed the heterosexual
      women in the sample to be distinguished from the lesbian women with 80% accuracy
      in classification of individual cases on the basis of four recollected attributes
      (imagined self as a male character, wished to become a mother, preference for
      boys' games, and considered a tomboy as a child). However, some heterosexual
      women reported much the same childhood behaviors as the majority of lesbian
      women, and some lesbian women reported much the same childhood behaviors as the
      majority of heterosexual women. Such diversity raises questions about the nature
      of the relationship between experiences in childhood and adult sexual
      orientation.

PMID- 7733802
TI  - Gender effects of romantic themes in erotica.
AB  - The hypothesis that women would be more aroused to explicit erotica containing a
      romantic (rather than nonromantic) theme while men would not be affected by the
      thematic manipulation was tested, 164 college students (91 male and 73 female),
      21 years of age and older, viewed one of four video vignettes taken from
      commercially available sexually explicit video tapes. The four videos represented
      the systematic manipulation of two independent variables: (i) high vs. low
      expression of love and affection (e.g, kissing, nongenital touching, and verbal
      expressions of caring); and (ii) high vs. moderate sexual explicitness (i.e.,
      "hard" vs. "soft" X-rated material). The results indicated that both male and
      female subjects rated the high explicit/high romantic vignette as significantly
      more arousing than the high explicit/low romantic vignette. Thus, the finding for
      males was contrary to expectations. The results are, however, consistent with the
      recent movement to romanticize highly explicit sexual material. Theoretical
      implications of these findings are examined.

PMID- 7733803
TI  - Clitoral blood flow increases following vaginal pressure stimulation.
AB  - The vascular responses of clitoral arteries to vaginal pressure stimulation in 10
      volunteer women were evaluated by Doppler ultrasonography. Pressure stimulations
      (20-160 mm Hg) along the lower third of the vagina increased blood velocity and
      flow into clitoral arteries in 9 of the 10 women. The latency and duration of the
      Doppler responses ranged from 0.1 to 1.6 sec and from 3.2 to 9.5 sec,
      respectively, and the response was associated with a blood flow increase of 4 to
      11 times the baseline prestimulation level. This response parallels that recorded
      in the cavernous arteries in men when a similar range of pressure stimulations
      are applied to the glans penis. Similar responses evoked in the male and female
      suggest a sexual synergy that may occur during intercourse in that such
      physiological responses and reflexes may be reciprocally reinforced.

PMID- 7733804
TI  - Sexual aggression and victimization in dating relationships among Chinese college
      students.
AB  - Sexual victimization in dating relationships among female Chinese college
      students in Hong Kong was studied. Findings were compared to Chinese males' self
      reports of sexual aggression. Nonstranger sexual victimization was common among
      Chinese female college students, especially for less intimate forms of sexual
      contact. Prevalence of sexual victimization was similar to that in North America
      for less intimate forms of contact but less prevalent for more intimate contact,
      including rape. A greater proportion of women than men reported the experience of
      several behaviors engaged in against a woman's will. These included kissing, and
      touching a woman's hand, knee, leg, or crotch.

PMID- 7733805
TI  - Is gender dysphoria dysphoric? Elevated depression and anxiety in gender
      dysphoric and nondysphoric homosexual and bisexual men in an HIV sample. HNRC
      Group.
AB  - Few if any studies before the AIDS epidemic suggested that male homosexuals may
      on average have higher levels of depression than male heterosexuals. However,
      several samples of homosexual and bisexual men in HIV studies suggest that
      depression and anxiety are high in these populations, and that this psychiatric
      morbidity began before the AIDS epidemic. We tested the hypothesis that high
      childhood gender nonconformity (CGN) is associated with depression and anxiety,
      and so might account for differences in these variables among samples of
      homosexuals. A total of 254 homosexual or bisexual male subjects were assessed
      for depression, anxiety, and associated symptoms using various self-report and
      interview measures, as well as for CGN (using the Freund Feminine Gender Identity
      scale, FGI). For comparison purposes only, we also evaluated the subjects for the
      DSM-III diagnosis of Ego-Dystonic Homosexuality. Highly gender nonconforming men
      (high FGI scores) were more likely to have current symptoms of anxiety and
      depression by self-report, and to have had a lifetime history of depression by
      clinical interview. This association was more often due to FGI items dealing with
      childhood than adulthood. When the FGI was broken into subscales by a prior
      factor analysis, stepwise regression suggested that the subscale measuring core
      gender identity nonconformity (so-called "gender dysphoria") was more reliably
      associated with depression and anxiety than were the factors measuring
      nonconformity in the areas of masculine and feminine gender roles, or
      genitoerotic (sexual) roles. This subscale was also the only FGI measure
      correlating with Ego-Dystonic Homosexuality. AIDS (CDC stage and HIV serostatus)
      and age did not account for these findings. We conclude that the often-reported
      higher levels of depression, anxiety, and associated symptoms among homosexual
      and bisexual men in AIDS studies are more common in the subgroup of such men who
      are gender dysphoric. Theoretical and clinical implications of these data are
      discussed.

PMID- 7733806
TI  - Harry Benjamin's first ten cases (1938-1953): a clinical historical note.
AB  - The value in studying Dr. Harry Benjamin's first gender dysphoria patients is in
      learning how they described themselves--without any books to read, without any
      other source of information, assuming that he or she was alone and unlike anyone
      else in the world--and before hardly any literature on the subject had been
      published. Just as today, Benjamin's earliest patients came to him self
      diagnosed. Even without the terminology currently available, their early
      descriptions of this unique phenomenon are identical with cross-gender identity
      patients who present themselves today: a recognition of the condition very early
      in their lives; the attempts at cross-dressing; the secrecy; the guilt; the
      unsuccessful attempts at suppressing desires and feelings; the episodic and
      continuous purging. These early individuals who suffered from gender conflicts
      had discovered Benjamin who would try to understand their unusual dilemma and be
      a barometer and a guide for the changes they would make. Their early
      individualistic perceptions provided insights that led to the birth of a new
      discipline. These 10 people must be lauded for their courage in seeking a
      description and a solution for a phenomenon that had no description and no
      treatment.

PMID- 7733807
TI  - Plasma thyroxine concentration in non-pregnant and lactating mink, and effect of
      dietary rapeseed oil in the reproduction period.
AB  - Effect of dietary rapeseed oil from 00-varieties of rapeseed (0, 1.5% or 3%
      respectively in the wet compounded diets) on plasma thyroxine (T4), reproductive
      performance and kit weight gain during lactation was investigated with 3 groups
      of each 20 mink females. Plasma T4, which has not previously been reported for
      female mink, was significantly lower in lactating than in non-pregnant females.
      Unlike in an earlier experiment with growing male mink, it was not affected by
      dietary rapeseed oil. Reproductive performance, female weight development, feed
      consumption, and kit weight gain was normal in all treatment groups and there
      were no significant effects of the experimental treatment.

PMID- 7733808
TI  - Hydrolyzed feather meal as feed component in diets for rainbow trout
      (Oncorhynchus mykiss) and effects of dietary protein/energy ratio on the
      efficiency of utilization of digestible energy and protein.
AB  - Two feeding trials were performed on rainbow trout of mean initial weights of 40
      and 50 g and lasting for 12 and 14 weeks, respectively. In trial 1, diets
      contained per kg 300 g fish meal and varying proportions of gelatinized maize
      starch plus either casein or hydrolyzed feather meal. Dietary crude protein
      content varied from about 27 to 53%. In trial 2, all diets had about 45% crude
      protein. Fish meal (300 g/kg) was replaced in 3 steps by hydrolyzed feather meal
      either without or with supplementation of L- lysine.HCl and/or DL-methionine. In
      trial 1, efficiency of utilization of digestible energy (DE) rose from 38 to 50%
      when the ratio digestible crude protein (DCP)/DE was increased from about 11 to
      17 g/MJ irrespective of the source of additional DCP, but did not further
      increase at higher ratios DCP/DE. Efficiency of utilization of DCP was about 50%
      as long as the ratio DCP/DE did not exceed 17 g/MJ. With progressing replacement
      of fish meal by hydrolyzed feather meal, efficiencies of utilization of DE as
      well as of DCP were reduced, the respective rates of reduction being about halved
      by supplementing lysine with no effect of supplementing methionine.

PMID- 7733809
TI  - Studies on limiting essential amino acids in grieves as source of dietary protein
      for rainbow trout (Oncorhynchus mykiss).
AB  - Diets were computed to contain equal concentrations of digestible crude protein
      either of wheat gluten (diet 1) or of grieves (diets 2-8). Per kg dry diet, 41 g
      crystalline amino acids were supplemented. All diets contained at least 1.2 g Lys
      per MJ digestible energy (DE). In diet 2, ratios of Met + Cys, Trp, Leu, Ile and
      Phe to Lys were about equal to those in diet 1. In each of diets 3-7, one of the
      respective amino acids, in diet 8 all five were replaced by Glu in the
      supplemented mixture of amino acids. Each diet was fed to triplicate groups of 20
      trout during a trial lasting 66 days. Trout fed the diet containing wheat gluten
      consumed more dry matter and showed higher growth rates as well as higher protein
      contents in their gained body mass than trout fed diets based on grieves.
      Supplementing Met plus Trp significantly improved dry matter intake, growth rate
      and protein content of gain, though not to the level of trout fed the wheat
      gluten diet, whereas Leu, Ile and Phe showed no such effect. When grieves were
      not supplemented with both Met and Trp, gain in body mass contained significantly
      more lipids. DE required per kg gain by trout fed wheat gluten, grieves + Met +
      Trp or grieves without supplementation of Met and Trp was 20.1, 21.2 and 29.9 MJ,
      respectively.

PMID- 7733810
TI  - [Report on the 4th symposium on 'vitamins and additives'].

PMID- 7733811
TI  - A comparative study of nutrient digestibility, kinetics of digestion and passage
      and rumen fermentation pattern in goats and sheep offered medium quality forages
      at the maintenance level of feeding.
AB  - The in vivo digestibility and the rates of degradation and passage of alfalfa hay
      (AH) and vetch straw (VS) were compared in three Granadina goats and three
      Segurena wethers fed at approximately maintenance level, using a change over
      design. The nylon bag technique was used to estimate the fractional rate of
      degradation of the feeds in the rumen. The fractional outflow rate of hay and
      straw particles was determined with chromium as a marker. No significant
      differences in the digestibility coefficients of nutrients between animal species
      were found. Nitrogen retention expressed as coefficients of both nitrogen intake
      and digested nitrogen was lower (P < 0.01) in goats than in sheep when VS was
      offered. There was no significant difference between goats and sheep in the
      effective degradability (measured at outflow rates in the range of 0.027 to 0.032
      h-1) of dry matter (DM) for either forage. However, the effective degradabilities
      of the neutral detergent fibre (NDF) and crude protein (CP) of VS were lower (P <
      0.01 and P < 0.001, respectively), in goats than in sheep. The degradation rates
      of DM, NDF and CP were not significantly different (P > 0.05) between goats and
      sheep. Also, the fractional rate of passage of particles from the rumen was not
      different (P = 0.056) between species, although there was a tendency for an
      increased outflow rate in goats. In a second experiment the effects of animal
      species, type of diet and frequency of feeding on rumen fermentation pattern were
      studied following a factorial design. Four goats and four wethers were used. They
      were randomly allocated to three dietary treatments: AH, VS or a 50:50 mixture of
      AH and VS (AH/VS). Rations were offered in two or three meals daily and samples
      of rumen content were obtained at 09.00, 11.00, 13.00, 15.00, 17.00 and 19.00 h.
      No difference in rumen pH was found between goats and sheep. Total volatile fatty
      acids and ammonia concentrations were higher (P < 0.001) in sheep than in goats.
      The molar proportions of acetate and isovalerate were higher (P < 0.01 and P <
      0.001, respectively) in goats than in sheep, whereas the opposite was true for
      the molar proportion of n-butyrate. Feeding frequency had a slight effect on the
      rumen parameters measured. It is concluded that only minor differences in the
      digestive capacity and rumen activity of sheep and goats can be expected when
      they are fed on medium quality forages.

PMID- 7733812
TI  - Volatile fatty acid concentrations, enzyme activities and microflora in the rumen
      contents of heifers during transition to pasture.
AB  - Observations were carried out on volatile fatty acid (VFA) concentrations, enzyme
      activities and the microflora of the rumen contents in heifers during transition
      from winter to pasture feeding and in the subsequent gazing cycles. After turn
      out to pasture, total VFA concentrations in the rumen contents of heifers
      significantly decreased from 107.7 to 88.7 mmol.l-1 (P < 0.01). After subsequent
      increase the total VFA concentrations reached their highest value (117.0 mmol.l
      1) in the 8th week of grazing. The proportion of the molar acetic acid
      concentration in the rumen content increased insignificantly whereas that of
      propionic acid decreased insignificantly. In the molar proportion of butyric acid
      no significant differences could be stated. In the subsequent weeks the molar
      proportions of acetic acid were rather balanced and ranged within 66.2 and 68.0
      mol%; the molar proportion of propionic acid insignificantly increased in the 4th
      week (18.7 mol%). Molar proportions of butyric acid on pasture insignificantly
      increased in week 3 (15.2 mol%) and appeared as balanced, later acquiring values
      between 14.0 and 14.8 mol%. The energetic yield of VFA production in the rumen of
      heifers decreased insignificantly from 73.6 to 72.15; the acetate: propionate
      ratio revealed an insignificant increase from 3.66 to 4.18. The enzyme activity
      of cellulase (endoglucanase E.C.3.2.1.4 and cellobiohydrolase E.C.3.2.1.91.)
      decreased significantly from 17.83 to 16.64 micrograms.ml-1 (P < 0.01); in the
      subsequent weeks, however, a significant increase could be observed. The enzyme
      activity of alpha-amylase (E.C.3.2.1.1.) decreased significantly (P < 0.05). In
      the 4th week a significant increase of the former occurred. The numbers of
      cellulolytic bacteria in the rumen content decreased significantly from 8.08 to
      7.61 log 10.ml-1 (P < 0.01) and then a significant increase to 8.39 log 10.ml-1
      was observed again in the 3rd week of grazing (P < 0.05). During pasture, a
      significant increase of the numbers of lactate-utilizing bacteria was recorded.
      As to the numbers of lactobacilli a significant decrease (P < 0.05) with a
      subsequent insignificant increase during grazing could be observed. Throughout
      the grazing season, the numbers of Streptococci reached values that surpassed
      those recorded during the winter feeding period. After transition from winter
      feeding to pasture the adaptation of rumen fermentation took four weeks.

PMID- 7733813
TI  - [Effect of the convertibility of energy (Q) on energy maintenance requirement and
      utilization and convertible energy for the assessment of ruminants. 1.
      Digestibility of energy and nutrients].
AB  - The energy metabolism was measured by means of indirect calorimetry in growing
      bulls with mean live weights of 290-420 kg and in wethers with mean live weights
      of 40-60 kg. The animals were fed 12 (bulls) and 8 rations (wethers) with high
      variation in the nutrients composition and with a range of energy
      metabolizability (q) between 0.74 and 0.47 on 3 steps of nutrition level
      (deposition, maintenance, underfeeding) as a rule. The energy digestibility of
      the 12 rations tested in growing bulls on the nutrition level maintenance was
      measured between 81.9 and 56.4% and that of the 8 rations tested in wethers was
      measured between 82.6 and 55.6%. On the high and middle nutrition levels the data
      of energy and nutrients digestibility in growing bulls and wethers were in good
      agreement, except the significant lower digestibility of crude protein in cattle.
      On the low nutrition level digestibility of energy, crude protein, crude
      cellulose and N free residual substances in wethers was 3-5 digestibility units
      lower than in bulls. The increase of nutrition level by 1 unit lowered the energy
      digestibility in bulls by 4.2 and the nutrients digestibility about 4-8%-units
      (0.7 for starch). In sheep the effect was not so high as in cattle. There were
      differences in the rumen physiological parameters between the animal species. In
      the growing bulls' rumen liquid the part of acetate was higher and the parts of
      propionate and butyrate were lower. The content of NH3 was higher in sheep. The
      increase of nutrition level caused higher amounts of volatile fatty acids in the
      two animal species with lowering the part of acetic acid and raising the parts of
      propionic and butyric acid.

PMID- 7733814
TI  - [Energy and nitrogen metabolism of pregnant and lactating sows in addition to the
      suckling piglets. 4. Chemical composition and energy content of the conception
      products, reproductive organs and the live weight gain or loss in pregnant or
      lactating sows].
AB  - The chemical composition and the energy content of the conception products, the
      reproductive organs and the live weight gains or losses of pregnant and lactating
      sows were determined in dependence on the litter number (1, 2 and 4) and the
      energy supply (120, 100 and 80% of requirement recommendation) of sows as well as
      on the course of gestation and lactation. The results will be used as a basis for
      factorial derivation of requirement recommendation. The deposition of protein and
      energy in the conception products in dependence on the time is characterized by
      an exponential function. The deposition of nutrients and energy in the conception
      products is increased with rising litter size. The deposition of nutrients and
      energy per fetus is lower in the litter number 1 than in the litter number 2 and
      4. The energy supply in the selected limits has no significant influence on the
      litter size as well as on the intrauterine deposition of nutrients and energy.
      The litter number, the energy supply as well as the course of gestation and
      lactation influence considerably the weight, the chemical composition and the
      energy content in the mammary gland. The chemical composition and the energy
      content of the live weight gains or losses of pregnant and lactating sows are
      strong affected by the energy supply. The increased energy supply of the pregnant
      sows is connected with increased live weight gains and with increased contents of
      dry matter, fat and energy however decreased contents of protein in the live
      weight gains. The live weight losses of the lactating sows are connected with
      mobilisation of body fat and body protein. The proportion of body fat to body
      protein degradation is increased with increased losses of body weight. Regression
      equations are calculated for the relationships between course of gestation and
      lactation respectively and deposition of protein and energy in the conception
      products, reproductive organs and maternal live weight gains or losses of sows.

PMID- 7733815
TI  - [Effect of the convertibility of energy (Q) on energy maintenance requirement and
      utilization and convertible energy for the assessment of ruminants. 2. Energy
      maintenance requirements and energy utilization].
AB  - In growing bulls (290-420 kg LW) and wethers (40-60 kg LW) the energy metabolism
      was measured by means of indirect calorimetry on 3 steps of energy intake
      (deposition, maintenance, underfeeding) as a rule with feeding 12 (growing bulls)
      resp. 8 rations (wethers) with a range of energy metabolizability (q) between
      0.74 and 0.47. Investigations were carried out in oxen previously with 9 rations
      with a range of q between 0.65 and 0.56 were completed by measurements of the
      energy metabolism with underfeeding and also analysed for the influence of q on
      energy maintenance requirement and energy utilization. In all 3 animal categories
      the energy maintenance requirement was not dependent on q significantly. On the
      nutrition level maintenance the mean energy maintenance requirement amounted to
      467 +/- 64 in growing bulls (n = 104), 533 +/- 53 in oxen (n = 44) and 323 +/- 59
      kJ ME/kg LW0.75.d in wethers (n = 32). The partial utilization of the
      metabolizable energy for deposition was influenced significantly (alpha = 0.05)
      by q in growing bulls only (kpf = -0.1495 + 0.9933q +/- 0.050). A differentiation
      of the utilization of metabolizable energy for deposition was demonstrable in
      wethers only with mean values of 50.7% (kf) and of 64.2% (km); km was also
      independent on q.

PMID- 7733816
TI  - Beet fed as such or ensiled with maize and fresh potatoes in diets for finishing
      bulls.
AB  - The use of beet for beef production after ensiling together with maize was
      studied in two experiments involving 112 and 114 White-blue bulls. In the first
      experiment maize silage (I) was compared with mixed silage of maize and fodder
      beet (II) or sugar beet (III) (ratio: 2/1, DM-basis). In the second experiment
      maize silage (I) was compared with mixed silage of 0.67 maize and 0.33 sugar beet
      (II) or maize silage and fresh sugar beet (ratio: 2/1, DM basis) (III) or fresh
      sugar beet and potatoes afterwards at 4% of the live weight and maize silage
      (IV). From day 113 onwards, mixed silage was also fed to group III and sugar beet
      were replaced by raw potatoes in group IV. The basic diet was always supplemented
      with concentrate at 0.75% of the live weight. In experiment 1 live weight gain
      was slightly but not significantly higher for the mixed silages, although daily
      net energy intake per kg metabolic weight was higher. Feed efficiency was not
      significantly different among groups. Mixed silages yielded more fat in the
      carcass. In the second experiment initial growth rates were not significantly
      affected by the use of sugar beet or mixed silages. Afterwards, they were
      increased in comparison with maize silage. Also in this experiment, daily net
      energy intake was increased by sugar beet, or by potatoes. Energy efficiency did
      not differ among groups. This experiment did not show significant differences for
      the carcass composition. However, EUROP fatness score was higher for diets
      containing one third sugar beet. Most meat quality parameters were not affected
      by the diets. Only the lightness was different between III and IV.

PMID- 7733817
TI  - Induction of a herpesvirus saimiri small RNA AU binding factor (AUBF70) activity
      and lymphokine mRNAs by T cell mitogens.
AB  - Herpesvirus saimiri (H. saimiri) can transform T lymphocytes and cause lymphoid
      tumors in rabbits and New World monkeys. H. saimiri-immortalized T cells express
      IL-2 and IL-4. The putative oncogenes of a group C strain of H. saimiri have been
      mapped to a region of the unique L-DNA which includes genes encoding four U-like
      small nuclear RNAs (HSUR1-HSUR4). Jurkat T cells express a 70 kD RNA binding
      factor (AUBF70) which binds HSUR2. Here we examined AUBF70 expression in resting
      and mitogen-stimulated human peripheral blood T cells and its sequence
      specificity and subcellular distribution. Band-shift assays demonstrated that
      resting human T cells express low amounts of AUBF70 which is induced by mitogen
      treatment. IL-2 and IL-4 mRNAs were co-induced with AUBF70 suggesting that AUBF70
      is a positive regulator of lymphokine gene expression. Normal resting, mitogen
      stimulated, and leukemic Jurkat T cells all express AUBF70 with virtually
      identical V8 proteolytic enzyme digestion patterns. Northern blots demonstrated
      that HSUR1 and HSUR2 are localized both in the nucleus and cytoplasm. HSUR2
      accumulate in the cytoplasm in the presence of actinomycin D, which is consistent
      with re-transport of HSURs to the nucleus by (an) unstable factor(s). We
      hypothesize that HSUR1 and 2 transport AUBF70 from the cytoplasm to the nucleus;
      in the nucleus, AUBF70 binds and stabilizes lymphokine transcripts. Increased
      stability of lymphokine mRNAs could contribute to oncogenic transformation
      induced by H. saimiri.

PMID- 7733818
TI  - Comparative amino acid sequence analysis of the major outer capsid protein (VP7)
      of porcine rotaviruses with G3 and G5 serotype specificities isolated in
      Venezuela and Argentina.
AB  - Seven porcine group A rotavirus strains isolated in Venezuela were shown to be
      antigenically related to serotype G3 (five strains) or to serotype G5 (two
      strains), whereas two strains isolated in Argentina were classified as serotype
      G5. The serological classification of eight of these strains was confirmed by
      sequence analysis of the gene encoding the VP7 glycoprotein. A high degree of
      homology was observed among strains belonging to the same G serotype, although
      some variations in the serotype-specific regions were detected among different
      strains. Comparison with the published VP7 amino acid sequences of serotype G3
      indicated that most porcine rotavirus strains are more closely related to each
      other and to human rotavirus strains than to rotavirus strains isolated from
      other species. Amino acid sequence comparison among serotype G5 porcine strains
      revealed that Venezuelan porcine isolates were more closely related to the
      American strain OSU, while the Argentinian strains had a higher similarity to the
      Australian strain TRF-41. This report confirms the worldwide distribution of
      these G serotypes among the porcine population.

PMID- 7733819
TI  - A single amino acid substitution at N-terminal region of coat protein of turnip
      mosaic virus alters antigenicity and aphid transmissibility.
AB  - The antigenic activity of the N-terminal region of coat protein of turnip mosaic
      virus (TuMV) aphid transmissible strain 1 and non-transmissible strain 31 was
      examined by using a panel of monoclonal antibodies (MAbs) raised against the two
      virus strains as well as antisera raised against several synthetic peptides from
      the N-terminal region of the protein. The reactivity of these antibodies was
      tested in ELISA and in a biosensor system (BIAcore Pharmacia) using virus
      particles, dissociated coat protein and synthetic peptides as antigens.
      Substitution of a single amino acid at position 8 in the coat protein of TuMV
      strain 1 abolished any cross-reactivity between MAbs to strain 1 and the
      substituted peptide (strain 31) in ELISA although some cross-reactivity was
      apparent in BIAcore inhibition experiments. In reciprocal tests with MAbs to
      strain 31 no cross-reactivity with the heterologous peptide was detected in
      either type of assay. The amino acid residue present at position 8 appears to
      play a critical role in the binding capacity of MAbs specific for the N-terminal
      region of TuMV. Antiserum to a synthetic peptide corresponding to residues 1-14
      of the protein of TuMV strain 1 was found to react strongly with dissociated coat
      protein and intact virus particles and was able to inhibit the aphid transmission
      of the virus. Antiserum to the corresponding peptide of strain 31 did not have
      this capacity.

PMID- 7733820
TI  - Molecular cloning and sequence determination of the peplomer protein gene of
      feline infectious peritonitis virus type I.
AB  - cDNA clones spanning the entire region of the peplomer (S) gene of feline
      infectious peritonitis virus (FIPV) type I strain KU-2 were obtained and their
      complete nucleotide sequences were determined. A long open reading frame (ORF)
      encoding 1464 amino acid residues was found in the gene, which was 12 residues
      longer than the ORF of the FIPV type II strain 79-1146. The sequences of FIPV
      type I and mainly -tPV type II were compared. The homologies at the N- (amino
      acid residues 1-693) and C- (residues 694-1464) terminal halves were 29.8 and
      60.7%, respectively. This was much lower than that between FIPV type II and other
      antigenically related coronaviruses, such as transmissible gastroenteritis virus
      of swine and canine coronavirus. This supported the serological relatedness of
      the viruses and confirmed that the peplomer protein of FIPV type I has distinct
      structural features that differ from those of antigenically related viruses.

PMID- 7733821
TI  - Cloning of the 3'-terminal region encoding movement and coat proteins of a Korean
      isolate of odontoglossum ringspot virus.
AB  - The 3'-terminal 1855 nucleotides (nts) of a Korean isolate of odontoglossum
      ringspot tobamovirus (ORSV-Cy) were cloned and sequenced. The sequence contained
      two open reading frames, which encode the cell-to-cell movement protein (MP) and
      coat protein genes, and are 912 nts and 477 nts long, respectively. The MP gene
      contained a conserved sequence motif of tobamoviruses and putative assembly
      origin of the viral RNA locating between 1117 nts and 1292 nts from the 3'-end.
      The 3' untranslated region (UTR) of the virus comprises 414 nts, includes nine
      pseudoknots and a tRNA-like structure domain containing aminoacyl acceptor arm
      and the anticodon hairpin loop coding for histidine.

PMID- 7733822
TI  - Immunological and molecular comparison of fowl adenovirus serotypes 4 and 10.
AB  - Some discussion has centered on whether fowl adenovirus (FAV) serotypes 4 and 10
      are distinct serotypes or in fact should be reclassified as a single serotype. We
      have undertaken a detailed characterisation of representatives of both serotypes
      in order to determine if types 4 and 10 should be grouped together or retained as
      distinct serotypes. Examination at the genomic level has revealed considerable
      similarities and few differences between these 2 serotypes. DNA cross
      hybridization failed to distinguish between them and restriction enzyme analysis
      demonstrated limited sequence differences. In vivo studies demonstrated the cross
      protection afforded by a natural route vaccination with serotype 4 FAV when
      chickens were challenged with serotype 10 FAV. On the basis of these studies it
      is suggested that these FAV serotypes be combined in future FAV classification.
      Physical maps for both serotype 4 and 10 have been constructed using the
      restriction enzymes Hpa I, Dra I, Nde I, Xba I and Not I for both serotypes and
      in addition Eco RI, Sfi I, Sma I and BglII for serotype 10.

PMID- 7733823
TI  - The clinical response of cattle experimentally infected with lumpy skin disease
      (Neethling) virus.
AB  - British cattle were inoculated with lumpy skin disease (Neethling) virus and
      their clinical signs observed over a three week period. Elevation of body
      temperature following infection was not found to be a consistent feature, and
      even in severe cases was limited to a peak temperature of 41 degrees C.
      Generalised lesions were seen 9-14 days post infection (p.i.), and the
      development of generalised infections did not appear to be dose related.
      Following intradermal inoculation lesions were detected from day 2 p.i. and first
      appearance and severity of local reaction appeared to be related to dose. Virus
      isolation was carried out on ocular, nasal and saliva swabs, and on buffy coat
      preparations. A transient viraemia was detected in two of eleven animals that did
      not show generalized signs; virus was not isolated from the secretions of seven
      animals without generalised signs. Virus was isolated from the peripheral
      secretions of an animal with generalised disease between 9 and 15 days p.i. and
      viraemia was detected in each of five animals with generalized signs. Delayed
      type hypersensitivity reactions following intradermal inoculation of immune
      cattle with LSDV were found to be maximal at 24 h after challenge.

PMID- 7733824
TI  - Banana bract mosaic virus: characterisation using potyvirus specific degenerate
      PCR primers.
AB  - Banana bract mosaic (BBMV) is a relatively new, non-persistently aphid
      transmitted disease of bananas in the Philippines. Partially purified
      preparations from infected plants contained low numbers of flexuous virions, 660
      to 760 nm in length, and a 38kDa protein, possibly the coat protein, which
      reacted with a general potyvirus antiserum in western blots. There were
      insufficient virions for conventional antiserum production or cDNA synthesis.
      Therefore, DNA was amplified using potyvirus-specific degenerate primers and
      reverse transcriptase PCR. The PCR products were cloned, sequenced and analysed
      and contained a 5' open reading frame of up to 150 amino acids and a 3'
      untranslated region of up to 190 nucleotides which were clearly related to the C
      terminal half of the coat proteins and the 3' untranslated regions, respectively
      of potyviruses. The BBMV open reading frame amino acid sequence was most similar
      to the C-terminal half of the maize dwarf mosaic potyvirus coat protein (71.3%
      similarity) and the BBMV 3' untranslated region was most similar to that of
      ornithogalum mosaic potyvirus (39.6% similarity). Our results show that BBMV is a
      distinct potyvirus and also demonstrate the application of virus group specific
      primers in the characterisation of previously undescribed viruses.

PMID- 7733825
TI  - Herpesvirus papio 2, an SA8-like alpha-herpesvirus of baboons.
AB  - Several SA8 isolates obtained from baboons were compared to the prototype SA8
      herpesvirus of African green monkeys. SDS-PAGE and restriction enzyme analyses
      revealed definite differences between green monkey and baboon isolates. DNA and
      amino acid sequences of the gB, gD and gJ glycoprotein genes exhibited
      substantial differences in variable regions. For the gB and gD, the amount of
      amino acid substitutions between SA8 and the baboon viruses was comparable to
      levels observed between analogous genes of SA8 & B virus or HSV1 & HSV2. Although
      a high degree of antigenic cross-reactivity was apparent, virus-specific
      antigenic determinants were also readily detected. Phylogenetic analyses
      supported separation of the baboon isolates and SA8 as distinct viruses. Taken
      together these results suggest that although closely related to SA8, the baboon
      viruses represent a distinct simian alpha-herpesvirus which we propose be
      designated Herpesvirus papio 2.

PMID- 7733826
TI  - Identification and analysis of an alcelaphine herpesvirus 1 (AHV-1) cDNA clone
      expressing a fusion protein recognized by AHV-1-neutralizing antisera.
AB  - Rabbit antiserum to psoralen-inactivated alcelaphine herpesvirus 1 (AHV-1)
      virions was shown to react specifically with AHV-1-infected cells by indirect
      immunofluorescence. Western blot analysis using this antiserum identified a 15-kD
      virion protein that was also detected in infected-cell proteins between 12 and
      144 h p.i., and a 37-kD protein present in infected cells between 24 and 120 h
      p.i. A cDNA library was constructed using mRNA obtained from AHV-1-infected fetal
      mouflon sheep kidney (FMSK) cells at 48 h p.i., when infected-cell proteins
      detected by antiserum were in abundance. Screening of the library with the rabbit
      anti-AHV-1 serum identified several positive clones. Southern blot analysis
      showed that one clone, designated 8'a, hybridized to a 4.4 kb HindIII fragment of
      AHV-1 DNA. This AHV-1 cDNA clone expressed a fusion protein that was recognized
      by serum from a naturally and asymptomatically infected white-bearded wildebeest
      (Connochaetes taurinus albojubatus). The insert was sequenced and found to
      contain 833 bp. A search of the GenBank database for related sequences revealed
      greater than 40% homology to several other gammaherpesviruses: herpesvirus
      saimiri, cottontail herpesvirus, and Epstein-Barr virus.

PMID- 7733827
TI  - Sequence analysis of the nucleoprotein genes of three enterotropic strains of
      murine coronavirus.
AB  - The nucleotide sequences of the nucleoprotein genes of three enterotropic strains
      of the murine coronavirus mouse hepatitis virus (MHV-Y, MHV-RI and DVIM) were
      determined and compared with previously reported sequences of three polytropic
      (respiratory) strains (MHV-A59, MHV-JHM and MHV-S). Greater than 92% homology was
      found among the six strains by pair-wise comparison at the nucleotide level. The
      genes encoded proteins of 451 to 455 residues and the deduced amino acid
      sequences were more than 91% homologous. A unique deletion of twelve nucleotides
      was found at the carboxy terminus of MHV-Y and a three nucleotide deletion was
      found in MHV-RI, which corresponded to the one previously reported in MHV-A59 and
      MHV-S. Two internal open reading frames were found within the coding region of
      the nucleoprotein, the smaller one was specific for the enterotropic strains. It
      could potentially encode a truncated version of the hypothetical protein
      described for MHV-A59 and MHV-S. Sequence relationship of the N gene showed no
      correlation with tissue tropism and no sequence or even single amino acid change
      unique to either tropism group was found. This indicates that the nucleoprotein
      of MHV probably has no part in the determination of the primary tissue tropism of
      an MHV strain. The role of the potential internal protein warrants further
      investigation.

PMID- 7733828
TI  - Ultrastructural study of the renal tubular system in acute experimental African
      swine fever: virus replication in glomerular mesangial cells and in the
      collecting ducts.
AB  - Despite the considerable attention given to kidney lesions in African swine fever
      (ASF), a number of questions remain to be answered. Structural and
      ultrastructural examination showed that a highly virulent isolate of ASF virus
      (Malawi 83) replicated in glomerular mesangial cells and renal collecting duct
      epithelial cells, with hyperplasia of the latter in infected pigs. Replication in
      mesangial cells may be due to their contact with the bloodstream, as well as to
      their phagocytic capacity and high metabolism rate. Virus replication in
      macrophages and endothelial cells of interstitial capillaries, and the necrosis
      of these infected cells gave rise to a large number of free virus in interstitial
      tissue. This, together with the lesser thickness of the basal membrane of
      collecting ducts in comparison to the rest of the tubular system, probably
      facilitates ASFV infection of tubular epithelial cells. Virus replication in
      these cells may account for the presence of virus in the urine of pigs with acute
      ASF where haematuria is not observed.

PMID- 7733829
TI  - Molecular characterization of two strains of the avian adeno-associated virus
      (AAAV).
AB  - An avian adeno-associated virus (AAAV) was isolated after propagating a field
      isolate of the CELO virus (fowl adenovirus serotype 1 (FAV1)) in embryonated
      eggs. The isolated dependovirus was compared with the known AAAV obtained from
      the American Type Culture Collection (ATCC VR-865). The genomes were analysed by
      digestion with several restriction endonucleases. Although both DNAs have the
      same size, most restriction enzymes produced different restriction patterns.
      Double digests were used to construct for the first time restriction maps for
      avian dependoviruses. The two DNAs rendered different restriction maps in which
      the different restriction sites were mainly located in the middle and right part
      of the genomes. The effect of these differences on the structure proteins was
      shown by western blot analysis. In the immunoblot, the immunofluorescence and
      immunodiffusion test the two dependoviruses were serologically indistinguishable
      and therefore can be regarded as two different strains of the same virus. To
      differentiate between both strains we named the original one as AAAV VR-865
      compared with the isolated AAAV DA-1.

PMID- 7733830
TI  - Emergence of a new bovine herpesvirus 1 strain in Australian feedlots.

PMID- 7733831
TI  - Sequence analysis of cDNA for the VP6 protein of group A avian rotavirus: a
      comparison with group A mammalian rotaviruses.
AB  - cDNA corresponding to the genomic segment 6 of avian rotavirus strain PO-13,
      which has group A common and subgroup I antigens, but does not hybridize in
      Northern blots with RNA probes from group A mammalian rotaviruses, was cloned and
      sequenced. When the deduced amino acid sequence was compared between strain PO-13
      and eight group A mammalian rotaviruses, the extent of homology ranged from 73
      75%. An alignment of the amino acid sequences allowed us to identify three amino
      acids (Positions 120, 317 and 350) that may contribute to determining the
      subgroup epitopes. A phylogenetic tree constructed on the basis of nucleotide
      substitutions in the VP6 gene of nine rotaviruses strongly suggests that the
      avian rotavirus is an ancestral prototype of mammalian rotaviruses.

PMID- 7733832
TI  - The embryonic beginning of virology: unbiased thinking and dogmatic stagnation.

PMID- 7733833
TI  - Treatment of hereditary ataxia with the levorotatory form of hydroxytryptophan.

PMID- 7733834
TI  - Dopamine D2 receptor and Tourette's syndrome.

PMID- 7733835
TI  - Multiple mononeuropathy and anti-neutrophil cytoplasmic autoantibody.

PMID- 7733836
TI  - Neoplastic meningitis presenting with ophthalmoplegia, ataxia, and areflexia
      (Miller-Fisher syndrome)

PMID- 7733837
TI  - A treatment for ataxia.

PMID- 7733838
TI  - Double-blind crossover study with levorotatory form of hydroxytryptophan in
      patients with degenerative cerebellar diseases.
AB  - OBJECTIVE: To determine whether treatment with the levorotatory form of
      hydroxytryptophan (L-5-hydroxytryptophan), a controversial experimental drug, can
      improve the conditions of patients with ataxia. DESIGN: A double-blind crossover
      study with the levorotatory form of hydroxytryptophan was performed in 39
      patients with degenerative cerebellar diseases. SETTING: Patients were selected
      from an ongoing prospective follow-up study at two university hospitals.
      PATIENTS: We studied 19 patients with Friedreich's ataxia, 13 with cerebellar
      atrophy, and seven with olivoponto-cerebellar atrophy. INTERVENTION: The
      levorotatory form of hydroxytryptophan was given orally in a dose of 1000 mg/d.
      Each treatment phase, with the levorotatory form of hydroxytryptophan or the
      placebo, lasted 10 months, after which the treatment of patients was crossed over
      to the other phase. MAIN OUTCOME MEASURES: Ataxia was documented and quantified
      by using a clinical score, posturography, and measurement of grip force and the
      rapid-syllable repetition rate. RESULT: The levorotatory form of
      hydroxytryptophan had no significant effect on cerebellar symptoms. CONCLUSION:
      Long-term treatment with a high dose of the levorotatory form of
      hydroxytryptophan does not improve the conditions of patients with ataxia.

PMID- 7733839
TI  - Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a
      double-blind drug-placebo cooperative study.
AB  - OBJECTIVE: To study the effect of the levorotatory form of 5-hydroxytryptophan on
      the cerebellar symptoms of Friedreich's ataxia. DESIGN: Cooperative double-blind
      study of the levorotatory form of 5-hydroxytryptophan vs placebo. SETTING: Twelve
      centers in research hospitals. PATIENTS: Twenty-six patients were included; 19
      completed the study (mean +/- SD age of patients, 25.9 +/- 8.1 years). Of these
      19 patients, eight were treated with placebo and 11 were treated with the drug.
      MAIN OUTCOME MEASURES: A semiquantitative scale for kinetic and static
      ("postural") cerebellar functions and quantitative measurements of time in
      standard tests that evaluated stance, speech, writing, and drawing. RESULTS: In
      the active treatment group, a significant decrease of the kinetic score was
      observed (P = .03), indicating an improvement in coordination. CONCLUSIONS: These
      results demonstrated that the levorotatory form of 5-hydroxytryptophan is able to
      modify significantly the cerebellar symptoms in patients with Friedreich's
      ataxia. However, the effect is only partial and not clinically major.

PMID- 7733840
TI  - Autoantibodies to glutamate decarboxylase in a patient with cerebellar cortical
      atrophy, peripheral neuropathy, and slow eye movements.
AB  - OBJECTIVE: To study the existence of autoimmunity against the cerebellum in
      patients with sporadic cortical cerebellar atrophy. DESIGN: The presence of
      autoantibodies against the cerebellum in the serum and cerebrospinal fluid
      samples that were obtained from patients with sporadic cortical cerebellar
      atrophy and control patients was investigated by using immunohistochemical
      techniques. SETTING: University hospital and research laboratory in Lyons,
      France. PATIENTS: Eight patients with cortical cerebellar atrophy that was
      associated with or without other neurological symptoms; 350 patients with various
      neurological diseases; and 33 normal, healthy subjects. OUTCOME MEASURES: Serum
      and cerebrospinal fluid anti-cerebellar autoantibodies were investigated by using
      indirect immunofluorescence techniques in rat cerebellum. To characterize antigen
      labeled by patient's serum, we used an immunotrapping enzyme activity assay of
      glutamate decarboxylase. RESULTS: Serum and cerebrospinal fluid samples that were
      taken from one patient with sporadic cortical cerebellar atrophy associated with
      peripheral neuropathy and slow eye movements contained anti-glutamate
      decarboxylase autoantibodies. CONCLUSIONS: These results suggest a participation
      of autoimmunity in the pathogenesis of some cases of sporadic cerebellar cortical
      atrophy and the involvement of the cerebellar gamma-aminobutyric acid-ergic
      system in the pathogenesis of this disease.

PMID- 7733841
TI  - Survival in institutionalized patients. Influence of dementia and loss of
      functional capacities.
AB  - BACKGROUND: Several studies have shown a negative correlation between dementia
      and survival. To our knowledge, the simultaneous effect of other factors has not
      been systematically studied in institutionalized patients. OBJECTIVE: To
      determine survival in demented inpatients compared with that in a matched
      population of nondemented patients institutionalized for other chronic
      debilitating diseases. DESIGN: The sample consisted of 213 patients with dementia
      and 157 patients without dementia. We studied the effect on survival of gender,
      age, loss of functional capacities, and cognitive functions with the method of
      Kaplan and Meier and with the model of Cox. RESULTS: Demented patients had
      significantly shorter survival when other factors were kept constant in the
      multivariate analysis. There was a strong correlation between survival and the
      degree of autonomy as measured by ability to walk, continence, and preserved
      activities of daily living. Survival was significantly shorter for men. No
      correlation was found with neuropsychological measures of severity of dementia or
      with age on admission. CONCLUSIONS: Survival of demented patients is shorter than
      that of patients institutionalized for other invalidating conditions. The lack of
      correlation between neuropsychological test results and survival indicates that
      in the population we studied, the severity of dementia did not predict length of
      survival. The data show that the combination of dementia and loss of functional
      capacities is the most important factor in predicting survival.

PMID- 7733842
TI  - Folstein vs modified Mini-Mental State Examination in geriatric stroke.
      Stability, validity, and screening utility.
AB  - OBJECTIVE: Two studies were conducted with the Folstein Mini-Mental State
      Examination (MMS) and the Modified Mini-Mental State Examination (3MS) to examine
      whether the expanded version is a more useful screening tool in stroke
      populations. DESIGN: Clinical utility of screening tests (MMS and 3MS) was
      evaluated in reference to neuropsychological performance and functional outcome
      in rehabilitation. SETTING: Medical rehabilitation unit of university-affiliated
      hospital. PATIENTS: Two groups (n = 77, and n = 70) of patients who were admitted
      consecutively. MAIN OUTCOME MEASURES: Neuropsychological performance and
      functional outcome (functional independence measure). RESULTS: The reliability,
      stability, and validity of the 3MS were established in the stroke population.
      Classification accuracy did not differ between the MMS and 3MS, although the 3MS
      had higher sensitivity. In detecting cognitive impairment when compared with the
      extended neuropsychological battery, both instruments were adequate in patients
      with left-sided cerebrovascular accidents and were ineffective in patients with
      right-sided cerebrovascular accidents. The 3MS correlated with some cognitive
      domains missed by the MMS, thus adding useful clinical information. Finally, the
      3MS was a significantly better predictor of functional outcome than the MMS.
      CONCLUSIONS: The 3MS was found to be a reliable, valid, and stable cognitive
      screening instrument in the stroke population. Classification accuracy indicates
      that both screening instruments are not strong in their ability to detect
      cognitive impairment in patients with stroke, especially in right-sided
      cerebrovascular accidents. The 3MS does have some advantages over the MMS; the
      expanded version of the screen not only provides additional cognitive information
      but also allows for better predicting of functional outcome.

PMID- 7733843
TI  - The 'preclinical phase' of probable Alzheimer's disease. A 13-year prospective
      study of the Framingham cohort.
AB  - OBJECTIVE: To evaluate the interval between the onset of detectable cognitive
      impairment and clinical diagnosis in individuals with probable Alzheimer's
      disease (AD), and to identify the pattern of the earliest changes in cognition in
      probable AD. DESIGN: Longitudinal follow-up of a community-based cohort sample.
      In 1976 through 1978, a screening neuropsychological examination was administered
      to Framingham Study participants. These subjects were then followed up
      prospectively for development of probable AD for up to 13 years. SETTING: This
      study was conducted at a community-based center for epidemiologic research.
      PARTICIPANTS: The surveillance sample consisted of 1045 participants in the
      Framingham Study aged 65 to 88 years who were free of dementia at the time of the
      neuropsychological screening examination. MAIN OUTCOME MEASURES: Scores on a
      group of neuropsychological tests were entered into a series of age- and
      education-adjusted multiple regression procedures, with the presence or absence
      of probable AD as the outcome variable. RESULTS: Considered individually, most of
      the screening neuropsychological measures were significantly related to later AD
      diagnosis. When stepwise regression procedures were employed, only measures of
      verbal memory and immediate auditory attention span remained significantly
      related to AD diagnosis. Of note, subjects later diagnosed with probable AD
      performed at higher levels than normal subjects on the Digit Span test at initial
      screening. Regression results were essentially unchanged even when the AD sample
      was restricted to those individuals for whom the screening examination preceded
      the clinical onset of dementia by 7 years or more. CONCLUSIONS: These findings
      support previous contentions that a "preclinical phase" of detectable cognitive
      deficits can precede the clinical diagnosis of probable AD by many years, and
      they also support the hypothesis that problems with secondary verbal memory are
      among the first signs of AD.

PMID- 7733844
TI  - Ischemic stroke in young adults. Experience in 329 patients enrolled in the Iowa
      Registry of stroke in young adults.
AB  - OBJECTIVES: To describe the likely causes of ischemic stroke in a population of
      young adults and to report the influence of strict algorithms on the diagnosis of
      the likely cause of stroke in this cohort. DESIGN: Between July 1, 1977, and
      January 1, 1993, we registered 329 young adults with ischemic stroke in our
      registry. Diagnostic studies were selected on a case-by-case basis. Presumed
      causes of stroke were determined using clinical information and the results of
      diagnostic tests. In each case, a second causative diagnosis was made using the
      criteria developed for a large clinical trial. SETTING: Patients referred to the
      Division of Cerebrovascular Diseases in the Department of Neurology at the
      University of Iowa Hospitals and Clinics, Iowa City, by physicians in Iowa and
      adjacent states. PATIENTS: Three hundred twenty-nine young adults (182 men and
      147 women) aged 15 to 45 years with ischemic stroke; 102 persons, 48 men and 54
      women, were aged 30 years or younger. RESULTS: Cerebral arteriography was
      performed in 227 cases, and the findings were abnormal in 146. Transthoracic
      echocardiography revealed abnormalities in 82 of 221 patients examined. We
      identified approximately 60 different disorders that were presumed to be the
      cause of stroke. There were no major changes in the frequency of subtype
      diagnoses between the first 144 patients and the subsequent 185. Use of strict
      diagnostic criteria increased the number of cases of stroke of undetermined
      etiology (from 45 to 113), and the number attributed to large artery
      atherosclerosis declined from 71 to 32. CONCLUSIONS: The causes of ischemic
      stroke in young adults are numerous. Because treatment options in this group are
      influenced by a presumed cause, an evaluation on a case-by-case basis is
      warranted. Our experience suggests that a likely cause will be detected in most
      cases and that a regimented battery of tests may not be required. If strict
      diagnostic criteria are used, the diagnosis of stroke of undetermined etiology
      considerably increases. While such strict criteria are important in clinical
      trials that test new interventions, the value of the application of such
      methodologies to an unusual population, such as stroke in young adults, needs
      clarification. In particular, the usefulness of categorizing a stroke as
      undetermined when two or more possible causes are identified needs to be
      explored.

PMID- 7733845
TI  - Prediction of functional outcome and tissue loss in acute cortical infarction.
AB  - OBJECTIVE: To compare the acute Allen's Prognostic Score, Canadian Neurological
      Score, and subacute Barthel Index as predictors of outcome functional status and
      infarct size at 3 months in patients with acute cortical infarction. DESIGN: A
      prospective study of acute stroke predictors and outcome measurements in a cohort
      of sequential hospitalized patients. PATIENTS: Fifty-one patients with acute
      cortical infarction and without previous disability assessed 24 hours after onset
      with Allen's Prognostic Score and the Canadian Neurological Score and at 7 days
      with the Barthel Index. MAIN OUTCOME MEASURES: Mortality, Barthel Index, and
      volumetric measurement of infarct size on computed tomography 3 months after
      stroke. RESULTS: There were seven deaths. The outcome Barthel Index was measured
      in all 44 survivors, of whom 29 had computed tomography at the time outcome was
      determined. In a multivariate analysis, functional outcome was best predicted by
      Allen's Prognostic Score, a score of less than -15 having a sensitivity of 82%
      and specificity of 97% in predicting a poor outcome (Barthel Index, < or = 12 or
      death). Volumetric tissue loss was predicted only by Allen's Prognostic Score (r
      = .62, P < .001). CONCLUSIONS: Allen's Prognostic Score is a robust predictor of
      both functional outcome and tissue loss in acute cortical infarction and has a
      potentially important role in the analysis of the results of acute stroke
      intervention trials.

PMID- 7733846
TI  - Morphologic cerebral asymmetries and handedness. The pars triangularis and planum
      temporale.
AB  - OBJECTIVE: To explore the relationship between morphologic cerebral asymmetries
      of the pars triangularis (PTr) and the planum temporale (PT) measured on three
      dimensional, gradient-echo, magnetic resonance imaging scans of healthy right-
      and left-handed subjects. DESIGN: (Blinded) comparison of healthy right- and left
      handed subjects who underwent magnetic resonance imaging. SETTING: The Seimens 1
      T Magnetom (Seimens, Iselin, NH) at the University of Florida Health Science
      Center, Gainesville. SUBJECTS: Healthy right-handed (n = 8) and left-handed (n =
      8) subjects matched for age, sex, and educational level. MAIN OUTCOME MEASURES:
      (1) Average length of the PTr (anterior ascending and anterior descending rami),
      (2) average length of the PT, (3) asymmetry quotients ([left-right]/[(left+right)
      (0.5)]) of the PTr and PT, and (4) combined asymmetry quotients of the PTr and
      PT. RESULTS: There was a significant leftward asymmetry of the PTr and PT in the
      right-handed subjects, but there was no significant asymmetry in the left-handed
      subjects. When the combined asymmetry quotient of the PTr and PT was calculated,
      the right-handed subjects had a leftward asymmetry (87.5% [n = 7]) or left was
      equal to right (12.5% [n = 1]), and the left-handed subjects had a leftward
      asymmetry (62.5% [n = 5]), left was equal to right (12.5% [n = 1]), or a
      rightward asymmetry (25% [n = 2]). In the left-handed subjects, writing posture
      seemed to predict these combined asymmetry quotients, ie, left-handed subjects
      using an inverted writing posture had a leftward asymmetry and left-handed
      subjects using a non-inverted writing posture had a rightward asymmetry of the
      perisylvian speech-language regions. CONCLUSIONS: On three-dimensional, gradient
      echo, magnetic resonance imaging scans, we found a significant leftward asymmetry
      of the PTr and PT. When the groups were divided into right- and left-handed
      subjects, the former had a significant leftward asymmetry of the PTr and PT,
      while the latter did not. Measurements of the PTr and PT appear to be important
      indexes of the known functional asymmetries of the perisylvian speech-language
      regions.

PMID- 7733847
TI  - Recurrent chiasmatic-hypothalamic glioma treated with oral etoposide.
AB  - BACKGROUND: Chiasmatic-hypothalamic gliomas are not amenable to surgical
      resection and therefore are treated with either radiotherapy or chemotherapy.
      Etoposide (VP-16), administered on a long-term oral schedule, represents a novel
      chemotherapeutic approach. PATIENTS AND METHODS: Fourteen patients (age range, 2
      to 15 years) were treated with etoposide following tumor progression as
      determined by clinical and neuroradiographic examinations. Thirteen patients had
      received prior radiotherapy, and 12 received prior nitrosourea-based
      chemotherapy. Etoposide was administered orally; each cycle consisted of 50 mg/m2
      per day on days 1 to 21 and days 36 to 57. Clinical and neuroradiographic
      examinations were performed from days 58 to 72 prior to the start of each cycle
      of therapy. Complete blood cell counts were performed weekly. RESULTS: Treatment
      related complications included partial alopecia (n = 7), diarrhea (n = 6), weight
      loss (n = 5), neutropenia (n = 4), and thrombocytopenia (n = 4). Three patients
      required a transfusion (ie, red blood cell [n = 3] and platelet [n = 2]
      transfusions), and one patient required antibiotic treatment of neutropenic
      fever. There were no treatment-related deaths. Fourteen patients were evaluable;
      in eight of these 14 patients, a response was demonstrated radiographically
      (complete response [n = 1], partial response [n = 4], and stable disease [n =
      3]), with a median duration of response of 8 months. CONCLUSIONS: Long-term
      treatment with oral etoposide was well tolerated by the patients in this study,
      and etoposide was a relatively nontoxic chemotherapeutic agent with apparent
      activity in this small cohort of patients who had recurrent chiasmatic
      hypothalamic gliomas.

PMID- 7733848
TI  - Natural history in proximal spinal muscular atrophy. Clinical analysis of 445
      patients and suggestions for a modification of existing classifications.
AB  - OBJECTIVES: To describe the natural history in all types of proximal spinal
      muscular atrophy (SMA) and to propose a modified classification scheme that takes
      the long-term course of SMA into account. DESIGN: Patients with proximal SMA were
      studied prospectively and retrospectively in a genetic study that was based on
      clinical and family data. PATIENTS: Four hundred forty-five patients with SMA
      were ascertained since 1985 through various departments of neurology and
      neuropediatrics, institutes of human genetics, and the German muscular dystrophy
      association (Deutsche Gesellschaft fur Muskelkranke, Freiburg, Germany). RESULTS:
      The study group was subdivided into patients with four types of SMA (ie, SMA
      types I, II, III, and IV) on the basis of achieved motor development and age at
      onset. Survival probabilities at 2, 4, 10, and 20 years of age were 32%, 18%, 8%,
      and 0%, respectively, in patients with SMA type I (those who were never able to
      sit) and 100%, 100%, 98%, and 77%, respectively, in patients with SMA type II
      (those who were able to sit but were unable to walk). Nineteen of 104 patients
      with SMA type II lost the ability to sit; this inability to sit was not of
      prognostic relevance. Patients with SMA type III (those who were able to walk
      [age at onset, younger than 30 years]) were subdivided into those with an age at
      onset before (SMA type IIIa) and after (SMA type IIIb) 3 years. The probabilities
      of being ambulatory at 10, 20, and 40 years after onset were 73%, 44%, and 34%,
      respectively, in patients with SMA type IIIa, and they were 97%, 89%, and 67%,
      respectively, in patients with SMA type IIIb. CONCLUSIONS: The definition of long
      term characteristics of SMA is helpful in providing medical care to families with
      members who have SMA and also in providing important information for future
      genotype-phenotype studies and therapeutic trials of patients with SMA. Our data
      indicate that the widely used classification schemes did not consider the broad
      spectrum of SMA so a practical modification was suggested.

PMID- 7733849
TI  - Neuropsychologic impairment in early HIV infection. A risk factor for work
      disability.
AB  - OBJECTIVE: To explore the functional significance of incident neuropsychologic
      impairment among initially asymptomatic subjects infected with human
      immunodeficiency virus. DESIGN: Prospective, observational cohort study of
      homosexual and bisexual men to examine the incidence of work disability related
      to the onset of neuropsychologic impairment. SETTING: A university clinical and
      behavioral research site in New York City. PARTICIPANTS: Sample of 207 homosexual
      and bisexual men; 123 were seropositive and 84 were seronegative. PRINCIPAL
      OUTCOME MEASURES: Incident work disability in the course of 4.5 years of follow
      up, with disability defined as a persistent (> or = 24 months) change in work
      hours (from 20 or more to less than 20 h/wk). RESULTS: Compared with seronegative
      control subjects (n = 72), the relative risk of work disability among initially
      asymptomatic seropositive men (n = 44) was 2.76 (95% confidence interval, 1.2 to
      6.5), nearly a threefold increase. Proportional hazards models show that this
      increased risk is attributable to the development of major neuropsychologic
      impairment in a subset (eight of 44) of the initially asymptomatic men, which is
      significantly associated with incident work disability (6/8 [75%]). Adjusting for
      symptom status and CD4+ cell count at the time of disability did not eliminate
      the increased risk associated with neuropsychologic impairment. CONCLUSIONS: In
      this cohort, the increased risk of work disability among initially asymptomatic
      human immunodeficiency virus-positive men was related to incident
      neuropsychologic impairment; such impairment predicted work disability
      independently of symptom status and CD4+ cell count over the follow-up period.
      Neuropsychologic impairment in the course of human immunodeficiency virus
      infection may indicate increased risk for poor outcomes over and above that
      associated with systemic disease.

PMID- 7733850
TI  - Hispanic. An epidemiologic meaningful term needed for public health planning.

PMID- 7733851
TI  - Hispanic. An epidemiologically meaningless term.

PMID- 7733852
TI  - Hispanics in Angloland.

PMID- 7733853
TI  - Personality and the inheritance of smoking behavior: a genetic perspective.
AB  - In contrast to the extensive research effort to understand the genetic
      contribution to alcoholism risk, there has been little research directed at
      understanding genetic influences on smoking behavior. Data from large twin
      studies in Scandinavia and Australia are consistent with a major genetic
      influence on the probability that an individual will become a smoker
      ("initiation") and will persist in the smoking habit once smoking has started
      ("persistence"). We use data from the 1988/1989 follow-up survey of the
      Australian NH&MRC twin panel to determine to what degree personality measures
      (Tridimensional Personality Questionnaire, Eysenck Personality Questionnaire-
      Revised) and attitudinal and sociodemographic variables (social and political
      conservatism, education, religious involvement) might account for genetic or
      environmental influences on smoking. While we find significant phenotypic
      associations between these variables and smoking, these are too modest to account
      for much of the genetic variance. Possible mechanisms by which this genetic
      variance may arise are discussed.

PMID- 7733854
TI  - Individual variability in responses to nicotine.
AB  - Individual variability in acute responses to nicotine, which may be defined as
      variable magnitude of effects following controlled dosing, is generally
      attributed to stable characteristics of tobacco users such as
      genetic/constitutional factors or to chronic behavioral factors (e.g., long-term
      use of other drugs). Often overlooked, however, is that such variability may also
      be due to the transient influence of the situational factors in which people
      consume nicotine, such as acute stress or physical activity. Results of selected
      studies from the author's laboratory provide examples of each of these sources of
      variability in nicotine responding on subjective, behavioral, and physiological
      measures. All studies used a nasal spray method of nicotine dosing or controlled
      smoking (paced puffing) to control acute nicotine exposure, an essential
      methodological feature of any research on individual differences in acute
      responses to nicotine. As an example of genetic/constitutional factors, gender
      differences in nicotine responding have begun to receive some attention, with few
      differences emerging. However, females may be more responsive than males to
      nonnicotine stimuli associated with smoking (e.g., sight and taste of smoke). In
      terms of chronic behavioral factors, long-term use of nicotine produces
      attenuation of most subjective and some behavioral effects of nicotine,
      reflecting chronic tolerance, and the possibility that chronic use of other drugs
      may alter responses to nicotine (i.e., cross-tolerance or cross-sensitization)
      deserves greater study. Of particular emphasis in this review is the modulating
      influence of acute situational factors on nicotine responding. Human studies have
      shown that magnitude of nicotine's subjective effects may depend on the predrug
      subjective state, level of physical activity vs. rest, and concurrent acute
      intake of other drugs, among other situational factors. Proper consideration of
      these situational factors may reveal the greatest source of individual
      variability in responding to nicotine and clarify the impact of more stable
      genetic/constitutional or chronic environmental factors.

PMID- 7733855
TI  - Personality, psychopathology, and nicotine response as mediators of the genetics
      of smoking.
AB  - Individual differences in psychopathology, personality, and nicotine responsivity
      and their biological bases are evaluated as mechanisms potentially mediating
      smoking heritability. Smokers are more likely to be high in neurotic traits
      (e.g., depression, anxiety, anger) and in social alienation (psychoticism,
      impulsivity, unsocialized sensation-seeking, low conscientiousness, low
      agreeableness) and low in achievement/socioeconomic status. Psychological and
      biological mechanisms putatively mediating these associations are reviewed. It is
      concluded that a number of relatively indirect and complex processes, as well as
      more direct (e.g., self-medication for psychopathology, nicotine sensitivity),
      mediate the inheritance of smoking behavior.

PMID- 7733857
TI  - Individual differences in sensitivity to nicotine: implications for genetic
      research on nicotine dependence.
AB  - Recent evidence suggests that cigarette smoking has a heritability index around
      53%. While related research on underlying mechanisms also supports the idea that
      genetic factors contribute to nicotine dependence--as well as to cofactors such
      as substance use and mood disorders--the nature of the behavioral traits and
      biological capacity for reinforcement that constitutes vulnerability to nicotine
      dependence is not well understood. The present review explores the problem of why
      some people become highly nicotine dependent, others develop a pattern of
      occasional use, and still others avoid the drug entirely despite extensive
      exposure and widespread experimentation with tobacco in the population. Recent
      research--both infrahuman and human--suggests that vulnerability to nicotine
      dependence is related to high initial sensitivity to nicotine and that the
      development of tolerance is more rapid and self-administration more extensive in
      such individuals. Relevant findings from neuroscience and biobehavioral research
      are reviewed in order to identify variables and methodologies that might improve
      the reliability and validity of behavioral and molecular genetic studies on
      cigarette smoking. The integration of research in these areas may lead to new
      insights in the understanding of nicotine dependence as well as to improved
      techniques for prevention and treatment.

PMID- 7733856
TI  - Genetic and environmental aspects of the role of nicotinic receptors in
      neurodegenerative disorders: emphasis on Alzheimer's disease and Parkinson's
      disease.
AB  - As neurodegenerative disorders are better characterized, the importance of
      genetic and environmental interactions is becoming more evident. Among the
      neurodegenerative disorders, Alzheimer's disease and Parkinson's disease are both
      characterized by large losses of nicotinic binding sites in brain. In addition,
      losses in nicotinic receptors occur during normal aging. Chronic administration
      of nicotine in man or experimental animals increases the number of nicotinic
      receptors in brain. Nicotine has been shown to possess some neuroprotective
      properties for both cholinergic and dopaminergic neurons. These neuroprotective
      properties, when better understood, may provide important information on normal
      aging and neurodegenerative disorder related neuronal cell death. Understanding
      the functional aspects of neuronal nicotinic receptor subtypes may lead to
      successful therapeutic treatments or disease preventative strategies for
      neurodegenerative disorders.

PMID- 7733858
TI  - Differential effects of nicotine in inbred and selectively bred rodents.
AB  - The present review summarizes information about strain differences in the effects
      of nicotine. Earlier studies reported that rats selectively bred for behavioral
      differences (Maudsley, Roman) were differentially sensitive to the
      activating/depressing effects of nicotine, but few mechanistic studies were
      carried out. On the other hand, Collins and colleagues have conducted a
      comprehensive series of studies on inbred and crossbred mice, concluding that
      functional differences in nicotinic sensitivity can be but are not necessarily
      associated with differences in nicotine receptors. There is also consistent
      animal literature suggesting an association between alcohol and nicotine
      sensitivities. Finally, differences to nicotine have only recently been
      discovered in the Flinders Line rats, selectively bred for differences in
      sensitivity to an anticholinesterase agent. Some of the differences in nicotine
      sensitivity may depend upon underlying differences in muscarinic sensitivity, in
      nicotinic receptors, and/or dopaminergic mechanisms.

PMID- 7733859
TI  - The psychopharmacological basis of nicotine's differential effects on behavior:
      individual subject variability in the rat.
AB  - Nicotine, the presumed active pharmacological agent in tobacco, produces variable
      effects on behavior that are at best described as "paradoxical" in nature. Thus,
      nicotine, via tobacco use in humans or nicotine administration in experimental
      animals, tends to transpose behavior depending on predrug baseline rates of
      behavior. High rates of behavior appear to be reduced, while low rates of
      behavior appear to be increased by nicotine. This work further proposes that
      nicotine's variable effects on behavior may be related to its capacity to act as
      a behavioral agonist and/or antagonist via its ability either to activate or to
      desensitize distinct central nicotinic acetylcholinergic receptors (nAChR's).
      Nicotine is portrayed as a neuronal modulating agent that can affect behavior
      contingent upon the genetic makeup of the individual subject being studied.
      Depending on the structure, function, and location of distinct nAChR's, nicotine
      appears to be able to induce a wide range of behavioral effects important to the
      tobacco user. However, this does not rule out the role the importance that other
      biogenic amine systems (i.e., serotonin or dopamine) may have in the genetics of
      tobacco use or nicotine's variable effects on behavior.

PMID- 7733860
TI  - DNA markers associated with high versus low IQ: ethical considerations.

PMID- 7733861
TI  - Genetic, environmental, and situational factors mediating the effects of nicotine
      -an introduction.

PMID- 7733862
TI  - Psychiatric comorbidity of smoking and nicotine dependence.
AB  - Recent epidemiologic studies have revealed that comorbidity of psychiatric
      disorders is far more pervasive than previously suspected. Strong associations
      have been reported between specific substance use disorders and between any
      mental disorder and any substance use disorder. This report focuses on
      comorbidity of nicotine dependence, a substance use disorder on which little
      epidemiologic information is available. Data come from an epidemiologic study of
      approximately 1000 young adults in southeast Michigan, in which the NIMH-DIS,
      revised according to DSM-III-R, was used. Lifetime prevalence of nicotine
      dependence was 20%. Males and females with nicotine dependence had increased odds
      for alcohol and illicit drug disorders, major depression, and anxiety disorders,
      compared with nondependent smokers and nonsmokers combined. Major depression and
      any anxiety disorder were associated specifically with nicotine dependence.
      Increased odds for alcohol or illicit drug disorders were observed also in
      nondependent smokers, compared to nonsmokers. History of early conduct problems
      increased the odds for nicotine dependence among smokers. Potential mechanisms in
      the comorbidity of nicotine dependence are discussed.

PMID- 7733864
TI  - Translation in vivo of 5' untranslated-region splice variants of human surfactant
      protein-A.
AB  - Transcripts of human SP-A genes, SP-A1 and SP-A2, undergo alternative splicing of
      5' untranslated-region exons. We reverse-transcribed and amplified free
      cytoplasmic and polysome-bound RNA and showed that (a) all splice variants of
      both genes are translated in vivo, (b) the relative translatability of splice
      variants can differ among individuals, and (c) the relative levels of different
      SP-A splice variants differ among individuals.

PMID- 7733865
TI  - Levels of pyrroloquinoline quinone in various foods.
AB  - The levels of free pyrroloquinoline quinone (PQQ) in various foods were examined
      by the use of gas chromatography-mass spectrometry. PQQ was extracted from the
      samples, after addition of [U-13C]PQQ as internal standard, with n-butanol and
      Sep-Pak C18 cartridges. After derivatization of PQQ with phenyltrimethylammonium
      hydroxide, molecular peaks at m/z 448 and 462 were used for detection of PQQ and
      [U-13C]PQQ respectively, by selected ion monitoring. Free PQQ could be detected
      in every sample in the range 3.7-61 ng/g or ng/ml. Since its levels in human
      tissues and body fluids are 5-10 times lower than those found in foods, it is
      probable that PQQ existing in human tissues is derived, at least partly, from the
      diet.

PMID- 7733866
TI  - Streptomyces K15 active-site serine DD-transpeptidase: specificity profile for
      peptide, thiol ester and ester carbonyl donors and pathways of the transfer
      reactions.
AB  - The Streptomyces K15 transferase is a penicillin-binding protein presumed to be
      involved in bacterial wall peptidoglycan crosslinking. It catalyses cleavage of
      the peptide, thiol ester or ester bond of carbonyl donors Z-R1-CONH-CHR2-COX-CHR3
      COO- (where X is NH, S or O) and transfers the electrophilic group Z-R1-CONH-CHR2
      CO to amino acceptors via an acyl-enzyme intermediate. Kinetic data suggest that
      the amino acceptor behaves as a simple alternative nucleophile at the level of
      the acyl-enzyme in the case of thiol ester and ester donors, and that it binds to
      the enzyme.carbonyl donor Michaelis complex and influences the rate of enzyme
      acylation by the carbonyl donor in the case of amide donors. Depending on the
      nature of the scissile bond, the enzyme has different requirements for
      substituents at positions R1, R2 and R3.

PMID- 7733867
TI  - Human mast cell tryptase isoforms: separation and examination of substrate
      specificity differences.
AB  - Tryptases are trypsin-like enzymes found in mast cell granules that appear to
      exist as tetramers. These enzymes are not controlled by blood plasma proteinase
      inhibitors and only cleave a few physiological substrates in vitro, including
      high-molecular-mass kininogen (HMMK) and vasoactive intestinal peptide (VIP).
      Purified human lung mast cell tryptase (HLT) contained two bands of approx.
      molecular mass 29 and 33 kDa on SDS/PAGE. These two forms of HLT have been
      separated by chromatography on a cellulose phosphate column, with the high
      molecular-mass form (high-HLT) being eluted with 10 microM heparin and the low
      molecular-mass form (low-HLT) subsequently eluted with 1 M NaCl. Removal of
      asparagine-linked carbohydrate caused both isoforms to run as single sharp bands
      on SDS/PAGE, differing slightly in molecular mass. Separation of these two
      isoforms of tryptase shows that tetramers consist of four homologous subunits
      rather than mixtures of the two isoforms. Using HMMK and VIP as substrates, these
      two forms of HLT were found to differ with regard to specificity and rate of
      cleavage. High-HLT initially cleaved HMMK at Arg-431 within the C-terminal
      anionic binding region of the molecule, whereas low-HLT cleaved HMMK
      simultaneously at multiple sites within the C-terminal portion of the molecule.
      On the basis of HPLC peptide mapping, each isoform also cleaved VIP at different
      sites. Comparison of cleavage rates based on the active-site concentrations of
      titrated isoforms showed that low-HLT cleaved HMMK more rapidly than did high
      HLT. These two isoforms may represent different gene products or they may result
      from post-translational modification.

PMID- 7733863
TI  - Physiological functions of endosomal proteolysis.

PMID- 7733868
TI  - Rapid activation of the heat shock transcription factor, HSF1, by hypo-osmotic
      stress in mammalian cells.
AB  - Osmoregulation is important to living organisms for survival in responding to
      environmental changes of water and ionic strength. We demonstrated here for the
      first time that exposure of HeLa cells to a hypotonic medium (30% growth medium
      and 70% water) prominently induced the binding activity of the heat shock
      transcription factor (HSF). Pretreatment of cells with cycloheximide did not
      inhibit the induction of HSF-binding activity, indicating that the mechanisms of
      induction are independent of new protein synthesis. The magnitude of hypo-osmotic
      stress-induced HSF-binding activity was comparable with that induced by heat
      shock. The induction, as monitored by gel-mobility-shift assay, occurred within 5
      min of hypo-osmotic stress and persisted at least up to 4 h in HeLa cells under
      the hypotonic conditions. Addition of sorbitol to the hypotonic medium abolished
      HSF activation. Hypo-osmotic stress-induced HSF binding could also be
      demonstrated in HeLa cells maintained in simple sorbitol solution by decreasing
      the sorbitol concentration from 300 mM to 200 mM or less. Competition analysis
      suggests that the effects of hypo-osmotic stress on HSF-binding activity was
      specific. Cross-linking experiments and Western-blot analysis demonstrated that
      hypo-osmotic stress induced trimerization of human heat shock factor 1 (HSF1) in
      intact HeLa cells, suggesting that trimer formation of HSF1 was responsible for
      inducing HSF-binding activity in hypo-osmotically stressed cells. However, unlike
      heat shock response, the activation of HSF by hypo-osmotic stress did not lead to
      accumulation of hsp70 mRNA in HeLa cells.

PMID- 7733869
TI  - A study of the stabilization of the oxyanion of tetrahedral adducts by trypsin,
      chymotrypsin and subtilisin.
AB  - Subtilisin and delta-chymotrypsin have been alkylated using 2-13C-enriched
      benzyloxycarbonylglycylglycylphenylalanylchloromethane. A single signal due to
      the 13C-enriched carbon was detected in both the intact subtilisin and delta
      chymotrypsin derivatives. The signal titrated from 98.9 p.p.m. to 103.6 p.p.m.
      with a pKa value of 6.9 in the subtilisin derivative and it is assigned to a
      tetrahedral adduct formed between the hydroxy group of serine-221 and the
      inhibitor. The signal in the delta-chymotrypsin derivative titrated from 98.5
      p.p.m. to 103.2 p.p.m. with a pKa value of 8.92 and it is assigned to a
      tetrahedral adduct formed between the hydroxy group of serine-195 and the
      inhibitor. In both derivatives the titration shift is assigned to the formation
      of the oxyanion of the tetrahedral adduct. delta-Chymotrypsin has been inhibited
      by benzyloxycarbonylphenylalanylchloromethane and two signals due to 13C-enriched
      carbons were detected. One of these signals titrated from 98.8 p.p.m. to 103.6
      p.p.m. with a pKa value of 9.4 and it was assigned in the same way as in the
      previous delta-chymotrypsin derivative. The second signal had a chemical shift of
      204.5 +/- 0.5 p.p.m. and it did not titrate from pH 3.5 to 9.0. This signal was
      assigned to alkylated methionine-192. We discuss how subtilisin and chymotrypsin
      could stabilize the oxyanion of tetrahedral adducts.

PMID- 7733870
TI  - Stimulation of NADH-dependent microsomal DNA strand cleavage by rifamycin SV.
AB  - Rifamycin SV is an antibiotic anti-bacterial agent used in the treatment of
      tuberculosis. This drug can autoxidize, especially in the presence of metals, and
      generate reactive oxygen species. A previous study indicated that rifamycin SV
      can increase NADH-dependent microsomal production of reactive oxygen species. The
      current study evaluated the ability of rifamycin SV to interact with iron and
      increase microsomal production of hydroxyl radical, as detected by conversion of
      supercoiled plasmid DNA into the relaxed open circular state. The plasmid used
      was pBluescript II KS(-), and the forms of DNA were separated by agarose-gel
      electrophoresis. Incubation of rat liver microsomes with plasmid plus NADH plus
      ferric-ATP caused DNA strand cleavage. The addition of rifamycin SV produced a
      time- and concentration-dependent increase in DNA-strand cleavage. No stimulation
      by rifamycin SV occurred in the absence of microsomes, NADH or ferric-ATP.
      Stimulation occurred with other ferric complexes besides ferric-ATP, e.g. ferric
      histidine, ferric-citrate, ferric-EDTA, and ferric-(NH4)2SO4. Rifamycin SV did
      not significantly increase the high rates of DNA strand cleavage found with NADPH
      as the microsomal reductant. The stimulation of NADH-dependent microsomal DNA
      strand cleavage was completely blocked by catalase, superoxide dismutase, GSH and
      a variety of hydroxyl-radical-scavenging agents, but not by anti-oxidants that
      prevent microsomal lipid peroxidation. Redox cycling agents, such as menadione
      and paraquat, in contrast with rifamycin SV, stimulated the NADPH-dependent
      reaction; menadione and rifamycin SV were superior to paraquat in stimulating the
      NADH-dependent reaction. These results indicate that rifamycin SV can, in the
      presence of an iron catalyst, increase microsomal production of reactive oxygen
      species which can cause DNA-strand cleavage. In contrast with other redox cycling
      agents, the stimulation by rifamycin SV is more pronounced with NADH than with
      NADPH as the microsomal reductant. Interactions between rifamycin SV, iron and
      NADH generating hydroxyl-radical-like species may play a role in some of the
      hepatotoxic effects associated with the use of this antibacterial antibiotic.

PMID- 7733871
TI  - Rabbit alpha-1-antiproteinase E: a novel recombinant serpin which does not
      inhibit proteinases.
AB  - A cDNA coding for the E isoform of alpha-1-antiproteinase (also called alpha-1
      antitrypsin or alpha-1-proteinase inhibitor) was isolated by oligonucleotide
      hybridization following immunochemical screening of the rabbit liver cDNA
      library. The deduced amino acid sequence of the E isoform showed 96.4% identity
      in 413 residues of the F and S-1 isoforms of rabbit alpha-1-antiproteinase. The N
      terminal half of the amino acid residues of the three isoforms was almost
      identical, but the putative reactive-site loop structure (P8-P'8) was
      significantly different in the various forms, the P1 site of the E form being
      glutamic acid. Interaction of the recombinant E form with the various proteinases
      was investigated by SDS/PAGE, followed by immunoblot analysis. The recombinant
      protein and trypsin formed a 62 kDa equimolar complex, which gradually became
      graded to the 37 kDa fragment through several intermediates. The E form also
      formed a complex of a similar size with elastase and became degraded to the 31
      kDa fragment. Several proteinases which cleaved the E form without forming a
      detectable complex on SDS/PAGE are chymotrypsin, protease V8, pancreas
      kallikrein, thermolysin, papain and ficin. Other proteinases, with a stringent
      substrate specificity, such as thrombin, factor Xa, plasmin, plasma kallikrein
      and cathepsin G, did not attack the E form. Unlike the F and S-1 forms of rabbit
      plasma alpha-1-antiproteinase, the recombinant E form did not inhibit the
      amidolytic and proteolytic activities of trypsin. Neither elastase nor protease
      V8 was inhibited by the E form. Thus the change in the amino acid residues in the
      reactive-site loop, probably in the P1 site, is responsible for the loss of
      inhibitory activity of rabbit alpha-1-antiproteinase E. The novel character of
      the E form could provide a new insight into the interaction of serpin and
      proteinases.

PMID- 7733872
TI  - Mammalian antioxidant protein complements alkylhydroperoxide reductase (ahpC)
      mutation in Escherichia coli.
AB  - The MER5 [now called the Aop1 (antioxidant protein 1) gene] was cloned as a
      transiently expressed gene of murine erythroleukaemia (MEL) cell differentiation
      and its antisense expression inhibited differentiation of MEL cells. We found
      that the Aop1 gene shows significant nucleotide sequence similarity to the gene
      coding for the C22 subunit of Salmonella typhimurium alkylhydroperoxide
      reductase, which is also found in other bacteria, suggesting it functions as an
      antioxidant protein. Expression of the Aop1 gene product in E. coli deficient in
      the C22-subunit gene rescued resistance of the bacteria to alkylhydroperoxide.
      The human and mouse Aop1 genes are highly conserved, and they mapped to the
      regions syntenic between mouse and human chromosomes. Sequence comparisons with
      recently cloned mammalian Aop1 homologues suggest that these genes consist of a
      family that is responsible for regulation of cellular proliferation,
      differentiation and antioxidant functions.

PMID- 7733873
TI  - Comparison of glucose-transporter-containing vesicles from rat fat and muscle
      tissues: evidence for a unique endosomal compartment.
AB  - Insulin-sensitive tissues (fat and muscle) express a specific isoform of glucose
      transporter protein, GLUT4, which normally resides in intracellular vesicular
      structures and is translocated to the cell surface in response to insulin. Here
      we provide a biochemical comparison of GLUT4-containing structures from fat and
      muscle cells. We demonstrate that, in spite of totally different protocols for
      cell homogenization and fractionation used for adipocytes as compared with
      skeletal-muscle tissue, GLUT4-containing vesicles from both sources have
      identical buoyant densities, sedimentation coefficients, and a very similar, if
      not identical, protein composition. The individual proteins first identified in
      GLUT4-containing vesicles from adipocytes (GTV3/SCAMPs proteins and
      aminopeptidase gp160) are also present in the analogous vesicles from muscle.
      Intracellular microsomes from rat adipocytes also contain GLUT1, a ubiquitously
      expressed glucose-transporter isoform. GLUT1 has not been detected in
      intracellular vesicular pool(s) from skeletal-muscle cells, probably because of
      its low abundance there. GLUT1 in adipocytes is excluded from GLUT4-containing
      vesicles, but is found in membrane structures which are indistinguishable from
      the former by all methods tested and demonstrate the same type of regulation by
      insulin. That is, the GLUT1- and GLUT4-containing vesicles have identical
      densities and sedimentation coefficients in sucrose gradients, and translocate to
      the cell surface in response to hormonal exposure. Also, we describe a simple
      procedure for the purification of native glucose-transporter vesicles from rat
      adipocytes. Overall, our data suggest the existence of a unique endosomal
      compartment in fat and muscle cells which is functionally and compositionally
      different from other microsomal vesicles and which is responsible for insulin
      sensitive glucose transport in these tissues.

PMID- 7733874
TI  - Fatty acyl-CoA esters inhibit glucose-6-phosphatase in rat liver microsomes.
AB  - In native rat liver microsomes glucose 6-phosphatase activity is dependent not
      only on the activity of the glucose-6-phosphatase enzyme (which is lumenal) but
      also on the transport of glucose-6-phosphate, phosphate and glucose through the
      respective translocases T1, T2 and T3. By using enzymic assay techniques,
      palmitoyl-CoA or CoA was found to inhibit glucose-6-phosphatase activity in
      intact microsomes. The effect of CoA required ATP and fatty acids to form fatty
      acyl esters. Increasing concentrations (2-50 microM) of CoA (plus ATP and 20
      microM added palmitic acid) or of palmitoyl-CoA progressively decreased glucose-6
      phosphatase activity to 50% of the control value. The inhibition lowered the Vmax
      without significantly changing the Km. A non-hydrolysable analogue of palmitoyl
      CoA also inhibited, demonstrating that binding of palmitoyl-CoA rather than
      hydrolysis produces the inhibition. Light-scattering measurements of osmotically
      induced changes in the size of rat liver microsomal vesicles pre-equilibrated in
      a low-osmolality buffer demonstrated that palmitoyl-CoA alone or CoA plus ATP and
      palmitic acid altered the microsomal permeability to glucose 6-phosphate, but not
      to glucose or phosphate, indicating that T1 is the site of palmitoyl-CoA binding
      and inhibition of glucose-6-phosphatase activity in native microsomes. The type
      of inhibition found suggests that liver microsomes may comprise vesicles
      heterogeneous with respect to glucose-6-phosphate translocase(s), i.e. sensitive
      or insensitive to fatty acid ester inhibition.

PMID- 7733875
TI  - Glycosphingolipid composition of rat placenta: changes associated with stage of
      pregnancy.
AB  - The composition of glycolipids and their changes in the placenta were
      investigated in the normal pregnant rat. Total lipid fractions extracted from the
      placenta between days 12 and 20 of pregnancy (day 0 = oestrus) were subjected to
      glycolipid analysis using DEAE-Sephadex chromatography, silica-gel HPLC, silica
      gel TLC, TLC/immunostaining, matrix-assisted secondary-ion mass spectrometry in
      the negative-ion mode and 1H NMR. Glycolipids identified in the rat placenta
      were: gangliosides GM3 (NeuAcLacCer and NeuGcLacCer) and GD3 (NeuAcNeuAcLacCer,
      NeuAcNeuGcLacCer and NeuGcNeuAcLacCer), and neutral glycolipids ceramide
      monosaccharide (CMH) (GlcCer), ceramide disaccharide (CDH) (LacCer), ceramide
      trisaccharide (CTH) (Gb3Cer) and ceramide tetrasaccharide (CQH) (Gb4Cer). The
      content of neutral glycolipids was higher than that of gangliosides throughout
      pregnancy. Of the neutral glycolipids, CMH and CTH predominated and the level of
      CDH was low at mid-pregnancy. During late pregnancy, CMH and CTH decreased and
      CDH increased markedly. CQH remained at a low level throughout pregnancy. Of the
      gangliosides, GM3 was predominant on days 12-16 and then decreased, whereas GD3,
      which was low on day 12, increased slightly on day 16 and maintained the same
      level thereafter. Immunohistochemical studies indicated that these changes in the
      expression of major gangliosides from GM3 to GD3 occurred in labyrinthine
      trophoblasts. Thus expression of these glycolipids appears to change markedly
      during pregnancy.

PMID- 7733876
TI  - The complete sequence of human lens gamma s-crystallin.
AB  - The complete sequence of human gamma s-crystallin has been determined and
      confirmed using a combination of MS methods, peptide sequencing and cDNA
      sequencing. Regions 21-35 and 102-107, which were previously assumed to be the
      same as the bovine sequence, differ from the bovine sequence at residues 22, 28,
      31 and 104. An additional six residues were also found to be different from the
      original sequence determined for Pakastani lenses. Whether these differences
      represent errors in the original sequence or two different sequences among human
      lens crystallins is not yet known.

PMID- 7733877
TI  - Molecular cloning and expression of catrocollastatin, a snake-venom protein from
      Crotalus atrox (western diamondback rattlesnake) which inhibits platelet adhesion
      to collagen.
AB  - A 50 kDa protein that inhibits platelet adhesion to collagen has been isolated
      from snake venom of Crotalus atrox (western diamondback rattlesnake) and has been
      named 'catrocollastatin'. The cDNA cloning of catrocollastatin has been
      accomplished. A full-length cDNA of 2310 bp with an open reading frame between
      nucleotides 51 and 1880 was obtained. The deduced amino acid sequence consists of
      609 amino acids. The cDNA-predicted amino acid sequence is highly similar to that
      of haemorrhagic metalloproteinase jararhagin from Bothrops jararaca venom, HR1B
      from Trimeresurus flavoviridis, Ht-e from C. atrox and trigramin from T.
      gramineus. Like jararhagin and HR1B, catrocollastatin is a multidomain molecule
      composed of an N-terminal domain, a metalloproteinase domain, a disintegrin-like
      domain and a cysteine-rich C-terminal domain. In the disintegrin-like domain, the
      frequently seen RGD (Arg-Gly-Asp) sequence is replaced by SECD (Ser-Glu-Cys-Asp).
      This cDNA was expressed in Spodoptera frugiperda (fall armyworm) (Sf9) insect
      cells using a baculovirus expression system. Like native catrocollastatin, the
      expressed protein is capable of selectively blocking collagen-induced platelet
      aggregation. This is the first full-length clone of a high-molecular-mass
      haemorrhagin to be expressed.

PMID- 7733878
TI  - Influence of phosphorylation on isoform composition and function of a microtubule
      associated protein from developing Artemia.
AB  - A novel 49 kDa protein, which exhibits nucleotide-dependent cross-linking of
      microtubules in vitro and localizes to ordered microtubule arrays by
      immunofluorescent staining, has been purified to apparent homogeneity from the
      brine shrimp, Artemia. Electrophoretic analysis involving isoelectric focusing
      and two-dimensional gels, supplemented by staining of Western blots with affinity
      purified antibody, revealed that the 49 kDa protein consists of five isoforms
      with pI values of 6.0-6.2. The amount of 49 kDa protein increased slightly, but
      its isoform composition did not change significantly, during development of
      Artemia gastrula to third-instar larvae. Treatment with alkaline phosphatase
      caused the 49 kDa protein to undergo a mobility shift on gel electrophoresis,
      and, by use of an antibody to phosphoserine, at least two isoforms of the protein
      were shown to be phosphorylated. The serine phosphate, presumably added by a post
      translational mechanism, did not influence binding of the 49 kDa protein to
      microtubules. Under conditions in which microtubules were cross-linked, the 49
      kDa protein failed to interact with actin filaments. Our results demonstrate that
      the 49 kDa protein, like other structural microtubule-associated proteins such as
      tau and MAP2, is composed of several isoforms, some of which are phosphorylated.
      This protein has the potential to regulate the spatial distribution of
      microtubules within cells but does not link microfilaments to one another or to
      microtubules.

PMID- 7733879
TI  - Aberrant mitochondrial respiration in the livers of rats infected with Fasciola
      hepatica: the role of elevated non-esterified fatty acids and altered
      phospholipid composition.
AB  - The non-esterified fatty acid (NEFA) content and phospholipid composition of
      mitochondria isolated from the livers of Wistar rats infected with Fasciola
      hepatica were examined in relation to the aberrant mitochondrial respiration
      previously reported [Rule, Behm, and Bygrave (1989) Biochem. J. 260, 517-523]. At
      2 weeks post-infection, elevated NEFA levels were associated with uncoupling of
      mitochondrial respiration that was reversible in vitro by the addition of BSA.
      State IV respiration rates showed a strong correlation with NEFA content. At 3
      weeks post-infection, NEFA content had increased further and uncoupled
      mitochondria no longer showed any response to BSA. 31P-NMR analyses of cholate
      extracts of mitochondria from infected livers at 3 weeks post-infection revealed
      a marked loss of several major phospholipid species with a concomitant increase
      in catabolic products, particularly glycerophosphocholine and
      glycerophosphoethanolamine. Similar changes were observed in microsomal extracts.
      The NEFA content and phospholipid composition of mitochondria isolated from
      infected, athymic nude rats were not significantly different from uninfected,
      athymic rats. These findings suggest that uncoupling of liver mitochondria during
      infection with F. hepatica is the result of phospholipase activation mediated by
      the immune system of the host.

PMID- 7733880
TI  - Methane-induced haemolysis of human erythrocytes.
AB  - Human erythrocytes were exposed to high concentrations of methane and nitrogen
      through the application of elevated partial pressures of these gas molecules.
      Cell leakage (haemolysis) was measured for cells exposed to these gases under a
      wide range of experimental conditions. Application of methane produces haemolysis
      at pressures far below the hydrostatic pressures known to disrupt membrane or
      protein structure. The effects of changes in buffer, temperature, diffusion rate
      and detergents were studied. Methane acts co-operatively with detergents to
      produce haemolysis at much lower detergent concentration than is required in the
      absence of methane or in the presence of nitrogen. At sufficiently high
      concentrations of methane, all cells are haemolysed. Increased temperature
      enhances the effect. Methane produces 50% haemolysis at a concentration of about
      0.33 M compared with about 7.5 M methanol required for the same degree of
      haemolysis.

PMID- 7733881
TI  - Cytoskeletal reorganization of human platelets induced by the protein phosphatase
      1/2 A inhibitors okadaic acid and calyculin A.
AB  - Okadaic acid (OA) and calyculin A (CLA), which are potent and specific inhibitors
      of serine/threonine protein phosphatases type 1 and 2A, have been shown to induce
      drastic changes in platelet morphology. The aim of this study was to analyse the
      molecular mechanisms of OA- or CLA-induced cytoskeletal reorganization, with a
      specific focus on microtubules and actin filaments. Confocal fluorescence
      microscopy revealed that OA or CLA altered the distribution of microtubules from
      marginal band arrangements to homogeneous patterns, consistent with the
      transmission-electron-microscopic finding that microtubules were fragmented and
      redistributed into pseudopod-like processes. In thrombin-activated platelets, OA
      or CLA induced extremely long pseudopods containing an array of microtubules and
      actin filaments, and a condensed mass of actin filaments in the centre of
      platelets. OA or CLA induced the constriction of actin filaments without an
      increase in filamentous (F)-actin, and also rather significantly inhibited actin
      polymerization in thrombin-activated platelets. Furthermore, neither OA or CLA
      enhanced phosphorylation of myosin light chain (MLC). By immunoprecipitation of
      platelet lysate with anti-alpha-tubulin antibody, a 90 kDa protein was co
      precipitated with tubulin and was predominantly phosphorylated in the presence of
      OA. As the time-dependent phosphorylation of 90 kDa protein correlated well with
      the reorganization of microtubules, these data suggest that phosphorylation and
      dephosphorylation of this protein might play a role in the regulation of
      microtubule organization. These findings indicate that OA or CLA induces
      reorganization of microtubules and actin filaments via the phosphorylation of a
      microtubule-associated 90 kDa protein and an MLC-phosphorylation-independent
      mechanism. mechanism.

PMID- 7733882
TI  - Phospholipase D-induced phosphatidate production in intact small arteries during
      noradrenaline stimulation: involvement of both G-protein and tyrosine
      phosphorylation-linked pathways.
AB  - To investigate membrane lipid metabolism during smooth-muscle activation, the
      role of phospholipase D (PLD) in the production of phosphatidate (PA) was studied
      in rat small arteries stimulated with noradrenaline. Incubation with
      [3H]myristate preferentially labelled phosphatidylcholine (PtdCho), and in the
      presence of 0.5% ethanol [3H]phosphatidylethanol ([3H]PEt) was formed,
      demonstrating PLD activity. Noradrenaline (NA) stimulation resulted in an
      increase in PtdCho derived [3H]PA and [3H]PEt formation, indicating PLD
      activation. Stimulation of [14C]choline release confirmed PLD-mediated hydrolysis
      of PtdCho. Propranolol, an inhibitor of PA phosphohydrolase, increased [3H]PA
      levels in non-stimulated tissue and decreased the rate of degradation of both
      [3H]PA and [3H]PEt, implying that this is an active route for PA metabolism in
      small arteries. However, [3H]diacylglycerol levels were not increased during NA
      stimulation. Fluoroaluminate increased [3H]PEt formation and [14C]choline
      release, whereas high K+ in the presence of alpha 1-adrenoceptor blockade did
      not. Pervanadate increased phosphotyrosine levels in small arteries, and markedly
      stimulated [3H]PEt formation and [14C]choline release. The combination of
      pervanadate and NA stimulation resulted in a dramatic increase in [3H]PEt
      formation, which was greater than the sum of the individual responses to the two
      agonists. Pervanadate and fluoroaluminate in combination appeared to give an
      additive response, whereas high K+ did not alter the pervanadate-induced
      formation of [3H]PEt. Phosphotyrosine levels were increased by NA in the presence
      of tyrosine phosphatase inhibitors. This effect was blocked by genistein, a
      tyrosine kinase inhibitor. These data demonstrate that in NA-stimulated small
      arteries PLD-induced PtdCho hydrolysis contributes to accumulation of PA, but not
      of diacylglycerol. Furthermore, regulation of PLD activity appears to require G
      protein and tyrosine-phosphorylation-linked pathways.

PMID- 7733883
TI  - Two site-directed mutations abrogate enzyme activity but have different effects
      on the conformation and cellular content of the N-acetylgalactosamine 4
      sulphatase protein.
AB  - The sulphatase family of enzymes have regions of sequence similarity, but
      relatively little is known about either the structure-function relationships of
      sulphatases, or the role of highly conserved amino acids. The sequence of amino
      acids CTPSR at position 91-95 of 4-sulphatase has been shown to be highly
      conserved in all of the sequenced sulphatase enzymes. The cysteine at amino acid
      91 of 4-sulphatase was selected for mutation analysis due to its potential role
      in either the active site, substrate-binding site or part of a key structural
      domain of 4-sulphatase and due to the absence of naturally occurring mutations in
      this residue in mucopolysaccharidosis type VI (MPS VI) patients. Two mutations,
      C91S and C91T, altering amino acid 91 of 4-sulphatase were generated and
      expressed in Chinese hamster ovary cells. Biochemical analysis of protein from a
      C91S cell line demonstrated no detectable 4-sulphatase enzyme activity but a
      relatively normal level of 4-sulphatase polypeptide (180% of the wild-type
      control protein level). Epitope detection, using a panel of ten monoclonal
      antibodies, demonstrated that the C91S polypeptide had a similar immunoreactivity
      to wild-type 4-sulphatase, suggesting that the C91S substitution does not induce
      a major structural change in the protein. Reduced catalytic activity associated
      with normal levels of 4-sulphatase protein have not been observed in any of the
      MPS VI patients tested and all show evidence of structural modification of 4
      sulphatase protein with the same panel of antibodies [Brooks, McCourt, Gibson,
      Ashton, Shutter and Hopwood (1991) Am. J. Hum. Genet. 48, 710-719]. The loss of
      enzyme activity without a detectable protein conformation change suggests that
      Cys-91 may be a critical residue in the catalytic process. In contrast, analysis
      of protein from a C91T cell line revealed low levels of catalytically inactive 4
      sulphatase polypeptide (0.37% of the wild-type control protein level) which had
      missing or masked epitopes, suggesting an altered protein structure or
      conformation. Subcellular fractionation studies of the C91T cell line
      demonstrated a high proportion of 4-sulphatase polypeptide content in organelles
      characteristic of microsomes. The aberrant intracellular localization and the
      reduced cellular content of 4-sulphatase polypeptide was consistent with the
      observed structural modification leading to retention and degradation of the
      protein within an early vacuolar compartment.

PMID- 7733884
TI  - Expression of active recombinant pallidipin, a novel platelet aggregation
      inhibitor, in the periplasm of Escherichia coli.
AB  - The platelet aggregation inhibitor pallidipin is a protein present in the saliva
      of the blood-sucking triatomine bug Triatoma pallidipennis. Expression of
      recombinant pallidipin in the periplasm of Escherichia coli was achieved by
      placing its coding sequence downstream of the alkaline phosphatase (APase) or trc
      promoter in frame with bacterial leader peptide DNA sequences derived from APase
      or from the periplasmic form of cyclophilin (Cph). In each case the DNA sequence
      of mature pallidipin was merged to the leader peptide coding part, either
      directly, or while introducing additional amino acids, in order to assess their
      influence on the activity of the leader peptidase and on the biological activity
      of the recombinant protein. All tested constructs gave rise to abundant
      periplasmic expression of pallidipin, which was then purified by a combination of
      cation- and anion-exchange chromatography followed by size-exclusion gel
      chromatography. Recombinant pallidipin had the expected molecular mass
      (approximately 19 kDa) and was correctly processed, as demonstrated by SDS/PAGE
      and N-terminal amino acid sequencing. The highest expression levels were obtained
      with the three APase-derived expression plasmids. Platelet aggregation tests
      revealed that E. coli-derived pallidipin was fully active, with an IC50 of 33-89
      nM, comparable with that of the native protein, except when an additional N
      terminal lysyl-isoleucyl dipeptide was present, which resulted in an IC50 more
      than ten times higher.

PMID- 7733885
TI  - Isolation and characterization of the chicken trypsinogen gene family.
AB  - Based on genomic Southern hybridizations and cDNA sequence analyses, the chicken
      trypsinogen gene family can be divided into two multi-member subfamilies, a six
      member trypsinogen I subfamily which encodes the cationic trypsin isoenzymes and
      a three-member trypsinogen II subfamily which encodes the anionic trypsin
      isoenzymes. The chicken cDNA and genomic clones containing these two subfamilies
      were isolated and characterized by DNA sequence analysis. The results indicated
      that the chicken trypsinogen genes encoded a signal peptide of 15 to 16 amino
      acid residues, an activation peptide of 9 to 10 residues and a trypsin of 223
      amino acid residues. The chicken trypsinogens contain all the common catalytic
      and structural features for trypsins, including the catalytic triad His, Asp and
      Ser and the six disulphide bonds. The trypsinogen I and II subfamilies share
      approximately 70% sequence identity at the nucleotide and amino acid level. The
      sequence comparison among chicken trypsinogen subfamily members and trypsin
      sequences from other species suggested that the chicken trypsinogen genes may
      have evolved in coincidental or concerted fashion.

PMID- 7733886
TI  - Molecular cloning, purification and in situ localization of human colon
      kallikrein.
AB  - We have cloned and characterized a full-length cDNA encoding tissue kallikrein
      from a human colon carcinoma cell line (T84). The nucleic acid sequence of the
      colon kallikrein cDNA is identical to that of renal/pancreatic or tissue
      kallikrein cDNA. Reverse-transcription PCR followed by Southern-blot analysis
      using specific oligonucleotide probes showed expression of tissue kallikrein in
      human colon, pancreas and kidney. Tissue kallikrein mRNA was localized in
      glandular epithelial cells (goblet cells) in colon by in situ hybridization
      histochemistry. Human colon kallikrein was purified to apparent homogeneity by
      DEAE-Sepharose Cl-6B, aprotinin-affinity, and HQ/M perfusion chromatography. The
      purified colon kallikrein migrated as a broad, 40-45 kDa band in SDS/PAGE and was
      recognized by antibodies to human tissue kallikrein. The linear displacement
      curves for the colon kallikrein in an RIA were parallel with the human tissue
      kallikrein standard curve, indicating their immunological identity. The N
      terminal sequence of the purified colon kallikrein matches completely with that
      of purified urinary or tissue kallikrein. These results indicate that human colon
      kallikrein is transcribed from the tissue kallikrein gene.

PMID- 7733887
TI  - Mutation-deletion analysis of a Ca(2+)-dependent phospholipid binding (CaLB)
      domain within p120 GAP, a GTPase-activating protein for p21 ras.
AB  - p120 GAP is a GTPase activating protein for p21 ras. It is a multidomain protein
      which exhibits sequence similarity with other GTPase-activating proteins, src,
      pleckstrin and a central portion of the protein kinase C conserved region 2
      domain known as CaLB (Ca(2+)-dependent phospholipid-binding). The presence of
      this CaLB motif has led to the speculation that p120 GAP may be a member of a
      family of structurally related proteins containing a Ca(2+)-dependent
      membrane/lipid-binding domain. Here we have studied the in vitro Ca(2+)-dependent
      phospholipid-binding properties of the isolated proposed CaLB sequence in human
      GAP and deduce that a phospholipid-binding sequence is indeed located between
      amino acids 606 and 648. Binding of phosphatidylserine and phosphatidylinositol,
      but not phosphatidylcholine, within this sequence is Ca(2+)-dependent, with an
      estimated EC50 for Ca2+ of approx. 1 microM. Using deletion-mutation analysis we
      have further defined the minimal boundaries for this in vitro phospholipid
      binding activity. p120 GAP amino acids 612-643 exhibit full phospholipid-binding
      activity, but further deletion of either amino acids 612-617 or amino acids 633
      648 significantly decreased or abolished phospholipid binding. These studies
      establish that amino acids 612-643 of p120 GAP indeed constitute a functional
      CaLB domain and thereby imply a role for Ca2+ in the regulation of p120 GAP
      association with cellular (membrane) phospholipids.

PMID- 7733888
TI  - Expression and site-directed mutagenesis of mouse prostaglandin E2 receptor EP3
      subtype in insect cells.
AB  - A cDNA encoding for mouse prostaglandin E2 (PGE2) receptor EP3 subtype was cloned
      from a mouse kidney cDNA library by PCR using terminal primers derived from the
      known sequence of mouse lung EP3 receptor cDNA. The cloned cDNA was confirmed by
      sequencing and was expressed in Trichoplusia ni (MG1) insect cells using a
      baculovirus expression system. A specific protein of 60 kDa was detected by
      immunoblot with antibodies generated against a unique decapeptide sequence
      present in the second extracellular loop of the EP3 receptor. Specific binding of
      [3H]PGE2 with a Kd of 3 nM was also found in the membrane fraction of the insect
      cells. Ligand binding of the receptor was further studied by site-directed
      mutagenesis. Arg-309 of the receptor was separately mutated to lysine, glutamate
      and valine. cDNAs of the wild-type and mutant EP3 receptors were respectively
      expressed and studied in MG1 insect cells. Binding studies indicated that both
      glutamate and valine mutant EP3 receptors had no binding of [3H]PGE2. On the
      contrary, the lysine mutant receptor exhibited an even tighter binding (Kd = 1.3
      nM) than the wild-type EP3 receptor. Immunoblot studies indicated that these
      receptors were expressed in a comparable amount in MG1 insect cells. These
      results suggest that Arg-309 of EP3 receptor may be essential in ligand binding
      through ionic interaction.

PMID- 7733889
TI  - Dexamethasone down-regulates the 85 kDa phospholipase A2 in mouse macrophages and
      suppresses its activation.
AB  - We have studied the effects of dexamethasone (dex) (i) on the level of the
      arachidonate-mobilizing phospholipase A2 (PLA2-85) in macrophages, (ii) on the
      stimulus-induced activation of this enzyme, and (iii) on the stimulus-induced
      release of arachidonate. Treatment of macrophages with 10 nM dex led to
      progressive reduction of PLA2-85 down to approx. 35% of control levels in 20 h in
      the absence of stimuli. This was accompanied by a partial inhibition of calcium
      ionophore-induced arachidonate release. In contrast, the ability of zymosan or
      phorbol ester to cause both persistent activation of PLA2-85 and arachidonate
      release was greatly reduced or abolished. However, the protein phosphatase
      inhibitor okadaic acid, previously shown to cause enhanced phosphorylation and
      persistent activation of PLA2-85, was still able to exert this effect on the dex
      suppressed PLA2-85. This suggests that the effect of okadaic acid was exerted at,
      or downstream of, the dex-sensitive step(s). Treatment with dex also led to
      inhibition of the characteristic changes in phosphoprotein labelling induced by
      phorbol ester or zymosan. However, phorbol-dibutyrate-binding isoforms of protein
      kinase C were not severely down-regulated. Thus dex was found to down-regulate
      PLA2-85 and, in addition, to affect one or more component(s) in the signal chain
      that normally leads to its activation. However, okadaic acid retained the ability
      to cause activation of PLA2-85.

PMID- 7733890
TI  - Determination of the structure of an N-substituted protoporphyrin isolated from
      the livers of griseofulvin-fed mice.
AB  - Feeding mice with griseofulvin, a widely used anti-fungal agent which induces
      protoporphyria as a side-effect, leads to the formation in the liver of two green
      pigments which have been shown to be porphyrin adducts. In this work, the major
      porphyrin adduct isolated from the livers of griseofulvin-fed mice has been
      characterized structurally using one- and two-dimensional NMR spectroscopy. The
      adduct was shown to be an N-alkylated protoporphyrin IX in which the whole of
      griseofulvin (less a hydrogen atom) is attached to a pyrrole ring nitrogen of the
      porphyrin. It was shown that the drug-to-porphyrin linkage is an an -O-CH2
      Npyrrole = linkage, to either the 4- or 6-position of ring a of griseofulvin. In
      an attempt to identify which pyrrole nitrogen is involved in this linkage, the 1H
      spectra of the free base and zinc complex of the adduct were compared with the
      corresponding spectra of the four regioisomers of N-methylprotoporphyrin. These
      comparisons indicated that the adduct isolated from the livers of griseofulvin
      fed mice is either the NC or the ND regioisomer, although a clear distinction
      between these two could not be made on the available evidence. The mechanism of
      formation of the adduct and its relation to griseofulvin-induced protoporphyria
      are discussed.

PMID- 7733891
TI  - Nerve growth factor stimulates a novel protein kinase in PC-12 cells that
      phosphorylates and activates mitogen-activated protein kinase kinase (MEK).
AB  - Activation of mitogen-activated protein kinase (MAP kinase) plays an important
      role in the cellular effects of nerve growth factor (NGF). Although the precise
      pathway by which NGF activates MAP kinase is not clear, several enzymes have been
      identified that may form a linear phosphorylation cascade, in which MAP kinase is
      activated by MAP kinase kinase (MEK). A key enzyme that links the ras-GTP complex
      to MEK is widely believed to be the raf kinase. However, immunoprecipitation
      experiments in PC-12 cells revealed that raf is not the major NGF-dependent MEK
      kinase [Zheng, Ohmichi, Saltiel and Guan (1994) Biochemistry 33, 5595-5599]. We
      have identified a protein kinase from PC-12 cells that catalyses both the
      phosphorylation and activation of MEK. This activity is stimulated 3-fold in
      cells treated with NGF. The partial purification on FPLC and characterization of
      this MEK kinase indicate that it is distinct from raf, MEK, MAP kinase and other
      previously described NGF-stimulated protein kinases. The activity of this enzyme
      is unaffected by direct addition to the assay of heparin, staurosporine, K252A
      and the heat-stable cyclic AMP-dependent kinase peptide inhibitor, but is
      slightly inhibited by NaF and calcium ions. Comparison of its behaviour on gel
      permeation and sucrose-density gradients indicates a molecular mass in the region
      of 50,000 Da. Moreover, isoelectric focusing of the enzyme revealed a pI of
      approx. 7.3. The kinase activity is specific for ATP as substrate with a Km of 11
      microM, and requires Mg2+ as a cofactor. Analysis of the activation of this
      enzyme in PC-12 cells transfected with a dominant inhibitory mutant of p21ras
      suggests that this MEK kinase resides downstream of ras in the MAP kinase
      activation pathway. Moreover, site-directed mutation of the residues on MEK that
      are phosphorylated by raf does not completely abrogate phosphorylation by the MEK
      kinase, suggesting that this enzyme may share some phosphorylation sites with
      raf, but also phosphorylates MEK on other sites.

PMID- 7733892
TI  - Analysis of carbohydrate transport across the envelope of isolated cauliflower
      bud amyloplasts.
AB  - Using isolated amyloplasts from cauliflower buds, we have characterized the
      interaction and transport of various carbohydrates across the envelope membrane
      of a heterotrophic plastid. According to our results, glucose 6-phosphate (Glc6P)
      and glucose 1-phosphate (Glc1P) do not share the same transport protein for
      uptake into cauliflower-bud amyloplasts. Glc6P-dependent starch synthesis is
      strongly inhibited in the presence of dihydroxyacetone phosphate (DHAP) or 4,4'
      di-isothiocyano-2,2'- stilbenedisulphonic acid (DIDS), whereas Glc1P-dependent
      starch synthesis is hardly affected by these compounds. Analysis of the Glc6P
      uptake into proteoliposomes reconstituted from the envelope proteins of
      cauliflower-bud amyloplasts indicate that Glc6P is taken up in a counter-exchange
      mode with Pi, DHAP or Glc6P, whereas Glc1P does not act as a counter-exchange
      substrate. Pi is a strong competitive inhibitor of Glc6P uptake (Ki 0.8 mM) into
      proteoliposomes, whereas Glc1P does not significantly inhibit Glc6P transport.
      Beside a hexose-phosphate translocator, these amyloplasts possess an envelope
      protein mediating the transport of glucose across the membrane. This translocator
      exhibits an apparent Km for glucose of 2.2 mM and is inhibited by low
      concentrations of phloretin, known to be a specific inhibitor of glucose
      transport proteins. Maltose inhibits the uptake of glucose (Ki 2.3 mM),
      indicating that both carbohydrates share the same translocator.

PMID- 7733893
TI  - Long-range conformational effects of proteolytic removal of the last three
      residues of actin.
AB  - Truncated derivatives of actin devoid of either the last two (actin-2C) or three
      residues (actin-3C) were used to study the role of the C-terminal segment in the
      polymerization of actin. The monomer critical concentration and polymerization
      rate increased in the order: intact actin < actin-2C < actin-3C. Conversely, the
      rate of hydrolysis of actin-bound ATP during spontaneous polymerization of Mg
      actin decreased in the same order, so that, for actin-3C, the ATP hydrolysis
      significantly lagged behind the polymer growth. Probing the conformation of the
      nucleotide site in the monomer form by measuring the rates of the bound
      nucleotide exchange revealed a similar change upon removal of either the two or
      three residues from the C-terminus. The C-terminal truncation also resulted in a
      slight decrease in the rate of subtilisin cleavage of monomeric actin within the
      DNAse-I binding loop, whereas in F-actin subunits the susceptibility of this and
      of another site within this loop, specifically cleaved by a proteinase from
      Escherichia coli A2 strain, gradually increased upon sequential removal of the
      two and of the third residue from the C-terminus. From these and other
      observations made in this work it has been concluded that perturbation of the C
      terminal structure in monomeric actin is transmitted to the cleft, where
      nucleotide and bivalent cation are bound, and to the DNAse-I binding loop on the
      top of subdomain 2. Further changes at these sites, observed on the polymer
      level, seem to result from elimination of the intersubunit contact between the C
      terminal residues and the DNAse-I binding loop. It is suggested that formation of
      this contact plays an essential role in regulating the hydrolysis of actin-bound
      ATP associated with the polymerization process.

PMID- 7733894
TI  - Secondary structure and biophysical activity of synthetic analogues of the
      pulmonary surfactant polypeptide SP-C.
AB  - Native pulmonary-surfactant-associated lipopolypeptide SP-C, its chemically
      depalmitoylated form and several synthetic analogues lacking the
      palmitoylcysteine residues were analysed for secondary structure in phospholipid
      micelles and for biophysical activity in 1,2-dipalmitoyl-sn-glycero-3-
      phosphocholine/phosphatidylglycerol/palmitic acid (68:22:9, by wt.). Compared
      with the native molecule, with the entire poly-valyl part in a known alpha
      helical conformation, depalmitoylated SP-C was found to be still mainly alpha
      helical, but with an approx. 20% decrease in the helical content. A synthetic
      hybrid polypeptide where the entire poly-valyl alpha-helical part of native SP-C
      had been replaced with the amino acid sequence of a transmembrane helix of
      bacteriorhodopsin is also predominantly alpha-helical. In contrast, synthetic SP
      C analogues lacking only the palmitoyl groups, by replacement of the
      palmitoylcysteine residues with cysteine, phenylalanine or serine, or lacking the
      positively charged amino acids by replacement with alanine, are considerably less
      alpha-helical than both native and depalmitoylated SP-C. The data indicate that
      the SP-C palmitoyl groups are important for maintenance of the alpha-helical
      conformation in parts of the polypeptide, and that the poly-valyl alpha-helical
      conformation is not fully formed in synthetic SP-C polypeptides. Furthermore, the
      helical structure of both native and depalmitoylated SP-C in
      dodecylphosphocholine micelles is very resistant to thermal denaturation,
      exhibiting ordered structure at 90 degrees C. The alpha-helical content grossly
      parallels the peptide-induced acceleration of the spreading of phospholipids at
      an air/water interface and the increase of surface pressure. The data suggest
      that the alpha-helical conformation itself, rather than just the covalent
      structure, is of prime importance for the biological function of synthetic
      pulmonary-surfactant peptides.

PMID- 7733895
TI  - The stimulus-sensitive H2O2-generating system present in human fat-cell plasma
      membranes is multireceptor-linked and under antagonistic control by hormones and
      cytokines.
AB  - Previous work demonstrated that human fat-cells possess a plasma-membrane-bound
      H2O2-generating system that is activated by insulin. Here we show that this
      system is under antagonistic control by various hormones and cytokines that
      typically act through several distinct receptor families. Similarly to insulin,
      oxytocin and tumour necrosis factor alpha acted as stimulators of NADPH-dependent
      H2O2 generation, whereas isoprenaline, a beta-adrenergic agonist, had inhibitory
      effects. Surprisingly, the acidic and basic isoforms of fibroblast growth factor
      as well as homodimeric platelet-derived growth factor AA and BB had antagonistic
      stimulatory and inhibitory effects on NADPH-dependent H2O2 generation. The agents
      tested acted at discrete ligand-specific receptors and their mechanisms of action
      were membrane-delimited and occurred in the absence of ATP. These findings
      implied that established pathways of signal transduction, including receptor
      kinases or second-messenger-dependent protein kinases A and C, were not involved
      and placed the stimulus-sensitive H2O2-generating system in a position comparable
      with adenylate cyclase. It was concluded that the stimulus-sensitive H2O2
      generating system of human fat-cells meets all criteria of a universal signal
      transducing system for hormones and cytokines that may link ligand binding to
      cell-surface receptors to changes in the intracellular redox equilibrium.

PMID- 7733896
TI  - Antagonistic effects of different members of the fibroblast and platelet-derived
      growth factor families on adipose conversion and NADPH-dependent H2O2 generation
      in 3T3 L1-cells.
AB  - 3T3 L1-cells, which undergo adipose conversion in vitro, possess a stimulus
      sensitive H2O2-generating system in their plasma membrane, and its properties are
      virtually identical with those of the insulin-sensitive human fat-cell oxidase
      [Krieger-Brauer and Kather (1992) J. Clin. Invest. 89, 1006-1013]. Insulin and
      insulin-like growth factor I were found to be active stimulators of NADPH
      dependent H2O2 generation. Surprisingly, the acidic (a) and basic (b) isoforms of
      fibroblast growth factor (FGF) as well as the AA and BB homodimers of platelet
      derived growth factor (PDGF) had antagonistic effects on NADPH-dependent H2O2
      generation in plasma membranes which were parallelled by corresponding changes in
      H2O2 accumulation in intact cells. bFGF and PDGF BB (which inhibit NADPH
      dependent H2O2 generation) prevented the adipose conversion of 3T3 L1
      preadipocytes, and this effect could be reversed by exogenously supplied H2O2.
      Conversely, aFGF and PDGF AA, which stimulated H2O2 generation, accelerated
      adipocyte conversion in the presence of insulin and were adipogenic in
      themselves. Consistently, expression of the adipocyte phenotype induced by
      insulin, dexamethasone and isobutylmethylxanthine was enhanced in the presence of
      exogenous hypoxanthine/xanthine oxidase, whereas antioxidants, such as N
      acetylcysteine or ascorbate, suppressed the process of differentiation. It is
      concluded that the H2O2 produced in response to hormones and cytokines may
      contribute to the development and maintenance of the differentiated state.

PMID- 7733897
TI  - Involvement of the Ca(2+)-dependent phosphorylation of a 20 kDa protein in the
      proliferative effect of high-density lipoproteins (subclass 3) on the
      adenocarcinoma cell line A549.
AB  - Previous studies from our laboratory demonstrated that high-density lipoproteins
      (subclass 3; HDL3) bind to sites specific for apolipoprotein AI on the human
      adenocarcinoma cell line A549 and that HDL3 binding promotes a mitogenic effect
      [Favre, Tazi, Le Gaillard, Bennis, Hachem and Soula (1993) J. Lipid Res. 34, 1093
      1106]. In the present study, we have examined the cell proteins that showed
      modified phosphorylation after binding of HDL3 to specific sites, and the roles
      of Ca2+ and protein kinase C. Native HDL3 (but not tetranitromethane-modified
      HDL3) and Ca2+ ionophore A23187 strongly enhanced the phosphorylation of a 20 kDa
      protein (x 3.6) and, to a lower extent, the phosphorylation of 24 and 28 kDa
      proteins (x 2.2 and 2.6 respectively). The two effectors were equally able to
      stimulate cell growth. Down-regulation of protein kinase C by a 24 h incubation
      of cells with phorbol myristate acetate prevented the effects of HDL3 on the
      phosphorylation of 24 and 28 kDa proteins. However, the extent of phosphorylation
      of the 20 kDa protein was not affected. In contrast, activation of protein kinase
      C by a short incubation with phorbol myristate acetate resulted in inhibition of
      proliferation and an increase in 24 and 28 kDa (but not 20 kDa) protein
      phosphorylation. These results suggest that HDL3 putative receptors exert their
      proliferative effect on A549 cells through activation of a Ca(2+)-dependent
      protein kinase. This kinase activity is not modulated by phorbol ester and thus
      may be a calmodulin kinase or an isoenzyme of protein kinase C that is
      independent of phorbol ester. It allows a subsequent 20 kDa protein to be
      phosphorylated.

PMID- 7733898
TI  - Mechanism of inhibition of Ca(2+)-ATPase by myotoxin a.
AB  - The peptide DCRQKWKCCKKGSG [myotoxin-(29-42)], corresponding to residues 29-42 of
      myotoxin a, inhibits the activity of the Ca(2+)-ATPase of skeletal muscle
      sarcoplasmic reticulum, with a Kd value of 19.4 microM at pH 7.5, in 100 mM KCl.
      The peptide YKQCHKKGGHCFPKEK, corresponding to residues 1-16 of myotoxin a, is a
      less potent inhibitor. Inhibition by myotoxin-(29-42) is reduced at low pH and at
      high ionic strength, suggesting that charge interactions are important in binding
      to the ATPase. Inhibition of the ATPase has been shown to follow from a decrease
      in the rate of dephosphorylation, with no effect on the rate of phosphorylation
      of the ATPase or on the rate of the Ca2+ transport step (E1PCa2-->E2P). Binding
      of myotoxin-(29-42) decreased the affinity of the ATPase for Ca2+ and Mg2+, and
      increased the rate of dissociation of the outer Ca2+ ion from the ATPase. Unlike
      the amphipathic peptide melittin, it is suggested that myotoxin-(29-42) does not
      bind significantly to the lipid bilayer portion of the sarcoplasmic reticulum.
      Fluorescence quenching studies suggest that it could bind to the ATPase in the
      vicinity of Cys-344 in the phosphorylation domain and Lys-515 in the nucleotide
      binding domain. Inhibition of the ATPase is observed when the ATPase is
      reconstituted in monomeric form in sealed vesicles, suggesting that aggregation
      of the ATPase is not involved in inhibition.

PMID- 7733899
TI  - Activation of the herpes simplex virus immediate-early gene promoters by
      neuronally expressed POU family transcription factors.
AB  - Herpes simplex virus immediate-early (IE) promoters contain the TAATGARAT motif
      which acts as a target site for the cellular POU family transcription factors Oct
      1 and Oct-2. Here we show that other members of the POU family that are expressed
      in sensory neurons can also affect IE promoter activity. In particular, two
      members of the Brn-3 family of POU proteins Brn-3a and Brn-3c can activate the IE
      1 and IE-3 promoters when co-transfected into fibroblasts and neuronal cells
      whereas a third member Brn-3b represses IE promoter activity. In contrast, Brn-3
      proteins cannot overcome the inhibitory effect of neuronal Oct-2 on IE promoter
      activity in co-transfections nor do they prevent transactivation of the IE
      promoters by the Oct-1-Vmw65 complex. The potential regulation of the IE
      promoters by several different neuronally expressed POU proteins during the
      initiation, maintenance and re-activation of latent infection in sensory neurons
      is discussed.

PMID- 7733900
TI  - Kinetic characterization of enzyme forms involved in metal ion activation and
      inhibition of myo-inositol monophosphatase.
AB  - Activation and inhibition of recombinant bovine myo-inositol monophosphatase by
      metal ions was studied with two substrates, D,L-inositol 1-phosphate and 4
      nitrophenyl phosphate. Mg2+ and Co2+ are essential activators of both reactions.
      At high concentrations, they inhibit hydrolysis of inositol 1-phosphate, but not
      4-nitrophenyl phosphate. Mg2+ is highly selective for inositol 1-phosphate (kcat.
      = 26 s-1) compared with the aromatic substrate (kcat. = 1 s-1), and follows
      sigmoid activation kinetics in both cases. Co2+ catalyses the two reactions at
      similar rates (kcat. = 4 s-1), but shows sigmoid activation only with the natural
      substrate. Li+ and Ca2+ are uncompetitive inhibitors with respect to inositol 1
      phosphate, but non-competitive with respect to 4-nitrophenyl phosphate. Both
      metal ions are competitive inhibitors with respect to Mg2+ with 4-nitrophenyl
      phosphate as the substrate. With inositol 1-phosphate, Ca2+ is competitive and
      Li+ non-competitive with respect to Mg2+. Multiple inhibition studies indicate
      that Li+ and Pi can bind simultaneously, whereas no such complex was detected
      with Ca2+ and Pi. Several sugar phosphates were also characterized as substrates
      of myo-inositol monophosphatase. D-Ribose 5-phosphate is slowly hydrolysed (kcat.
      = 3 s-1), but inhibition by Li+ is very efficient (Ki = 0.15 mM), non-competitive
      with respect to the substrate and competitive with respect to Mg2+. Depending on
      the nature of the substrate, Li+ inhibits by preferential binding to free enzyme
      (E), the enzyme-substrate (E.S) or the enzyme-phosphate (E.Pi) complex. Ca2+, on
      the other hand, inhibits by binding to E and E.S, in competition with Mg2+. The
      results are discussed in terms of a catalytic mechanism involving two metal ions.

PMID- 7733901
TI  - Evidence of a defined spatial arrangement of hyaluronate in the central filament
      of cartilage proteoglycan aggregates.
AB  - Aggregates of proteoglycans from the Swarm rat chondrosarcoma reassembled in
      vitro have been studied by rotary-shadowing electron microscopy, and shown to be
      similar to native structures that have never been dissociated [Morgelin, Engel,
      Heinegard and Paulsson (1992) J. Biol. Chem. 267, 14275-14284]. A hyaluronate
      with defined chain length (HAshort) has now been prepared by autoclaving high-Mr
      hyaluronate and fractionation to a narrow size distribution by gel filtration.
      Proteoglycan monomers, core protein, hyaluronate-binding region and link protein
      were combined with HAshort. Free chains of HAshort and reconstituted complexes
      with proteoglycan, link protein and aggrecan fragments were examined by electron
      microscopy after rotary shadowing. Length measurements showed that the
      hyaluronate was condensed to about half of its original length on binding intact
      aggrecan monomers, any aggrecan fragment or link protein alone. This strongly
      implies that hyaluronate adopts a defined spatial arrangement within the central
      filament of the aggregate, probably different from its secondary structure in
      solution. No differences in length were observed between link-free and link
      stabilized aggregates.

PMID- 7733902
TI  - Tropine dehydrogenase: purification, some properties and an evaluation of its
      role in the bacterial metabolism of tropine.
AB  - Tropine dehydrogenase was induced by growth of Pseudomonas AT3 on atropine,
      tropine or tropinone. It was NADP(+)-dependent and gave no activity with NAD+.
      The enzyme was very unstable but a rapid purification procedure using affinity
      chromatography that gave highly purified enzyme was developed. The enzyme gave a
      single band on isoelectric focusing with an isoelectric point at approximately pH
      4. The native enzyme had an M(r) of 58,000 by gel filtration and 28,000 by
      SDS/PAGE and therefore consists of two subunits of equal size. The enzyme
      displayed a narrow range of specificity and was active with tropine and
      nortropine but not with pseudotropine, pseudonortropine, or a number of related
      compounds. The apparent Kms were 6.06 microM for tropine and 73.4 microM for
      nortropine with the specificity constant (Vmax/Km) for tropine 7.8 times that for
      pseudotropine. The apparent Km for NADP+ was 48 microM. The deuterium of [3
      2H]tropine and [3-2H]pseudotropine was retained when these compounds were
      converted into 6-hydroxycyclohepta-1,4-dione, an intermediate in tropine
      catabolism, showing that the tropine dehydrogenase, although induced by growth on
      tropine, is not involved in the catabolic pathway for this compound. 6
      Hydroxycyclohepta-1,4-dione was also implicated as an intermediate in the
      pathways for pseudotropine and tropinone catabolism.

PMID- 7733903
TI  - Lysophosphatidic acid-induced Ca2+ mobilization in human A431 cells: structure
      activity analysis.
AB  - Lysophosphatidic acid (LPA; 1-acyl-sn-glycero-3-phosphate) is a platelet-derived
      lipid mediator that activates its own G-protein-coupled receptor to trigger
      phospholipase C-mediated Ca2+ mobilization and other effector pathways in
      numerous cell types. In this study we have examined the structural features of
      LPA that are important for activation of the Ca(2+)-mobilizing receptor in human
      A431 carcinoma cells, which show an EC50 for oleoyl-LPA as low as 0.2 nM. When
      the acyl chain at the sn-1 position is altered, the rank order of potency is
      oleoyl-LPA > arachidonoyl-LPA > linolenoyl-LPA > linoleoyl-LPA > stearoyl-LPA =
      palmitoyl-LPA > myristoyl-LPA. The shorter-chain species, lauroyl- and decanoyl
      LPA, show little or no activity. Ether-linked LPA (1-O-hexadecyl-sn-glycero-3
      phosphate) is somewhat less potent than the corresponding ester-linked LPA; its
      stereoisomer is about equally active. Deletion of the glycerol backbone causes a
      1000-fold decrease in potency. Replacement of the phosphate group in palmitoyl
      LPA by a hydrogen- or methyl-phosphonate moiety results in complete loss of
      activity. A phosphonate analogue with a methylene group replacing the oxygen at
      sn-3 has strongly decreased activity. All three phosphonate analogues induce cell
      lysis at doses > 15 microM. Similarly, the methyl and ethyl esters of palmitoyl
      LPA are virtually inactive and become cytotoxic at micromolar doses. None of the
      LPA analogues tested has antagonist activity. Sphingosine 1-phosphate, a putative
      messenger with some structural similarities to LPA, elicits a transient rise in
      intracellular [Ca2+] only at micromolar doses; however, cross-desensitization
      experiments indicate that sphingosine 1-phosphate does not act through the LPA
      receptor. The results indicate that, although many features of the LPA structure
      are important for optimal activity, the phosphate group is most critical,
      suggesting that this moiety is directly involved in receptor activation.

PMID- 7733904
TI  - Cloning and functional characterization of the human vasoactive intestinal
      peptide (VIP)-2 receptor.
AB  - A full-length clone encoding the human VIP-2 receptor was isolated from a human
      placenta cDNA library. The 1317-bp cDNA insert encodes a protein of 438 amino
      acids which is a member of the seven transmembrane domain G-protein-coupled
      receptor superfamily. Expression of the human VIP-2 receptor in COS-7 cells
      confered high affinity binding to [125I] VIP (IC50 = 0.93 nM), which was
      displaced by unlabeled PACAP-38 (IC50 = 6.2 nM). VIP and PACAP-38 were equipotent
      in stimulating accumulation of cAMP in COS-7 cells transfected with the human VIP
      2 receptor. Northern blot analysis revealed two VIP-2 receptor mRNAs of 4.6 kb
      and 2.3 kb in size which were expressed predominantly in the human skeletal
      muscle and to a lesser extent in the human brain, heart, pancreas and placenta.

PMID- 7733905
TI  - Platelet-derived growth factor isoforms PDGF-AA, -AB and -BB exert specific
      effects on collagen gene expression and mitotic activity of cultured human wound
      fibroblasts.
AB  - This study was designed to clarify the action of three different isoforms of PDGF
      (PDGF-AA, PDGF-AB and PDGF-BB) on the proliferation rate and collagen synthesis
      of fibroblasts cultured from normal human wounds. PDGF-AA and PDGF-BB down
      regulated both the steady-state levels of pro alpha 1 (I) and pro alpha 1 (III)
      collagen chain mRNAs and the production of collagen, both in a dose-dependent
      manner. Interestingly, low concentrations (1 ng/ml) of PDGF-AB up-regulated the
      expression of type I and III procollagen mRNAs by cultured wound fibroblasts,
      while under high concentrations (30 ng/ml) of PDGF-AB this effect changed to the
      opposite. The proliferation rate of wound fibroblasts was stimulated by PDGF-BB
      which elicited a dose-dependent (1-30 ng/ml) stimulation of cell proliferation,
      whereas PDGF-AB and -AA were less effective in this respect.

PMID- 7733906
TI  - Cell cycle dependent induction of apoptosis by somatostatin analog SMS 201-995 in
      AtT-20 mouse pituitary cells.
AB  - Somatostatin (SS) and its analogs exert direct antiproliferative effects in a
      variety of tumor cells not only by inhibiting the mitogenic signalling of growth
      factor receptor kinases, but also by inducing apoptosis. In this study, the
      apoptotic effect of the octreotide SS analog, SMS 201-995, was investigated in
      phase synchronized AtT-20 mouse pituitary tumor cells. SMS 201-995 added to cells
      synchronized in G1 or in G2 phases induces apoptosis which is manifested in the
      subsequent cell cycle. No evidence of apoptosis was seen in cells subjected to
      cell cycle arrest in G1 by lovastatin or in G2 with 160 nM staurosporine. SMS 201
      995 did not induce detectable apoptosis in unsynchronized cells which remained
      predominantly in G1 phase. These findings provide the first documentation that SS
      peptides regulate cell growth in G2 to induce apoptosis.

PMID- 7733907
TI  - Mutagenesis of human adenosine deaminase to active forms that partially resist
      inhibition by pentostatin.
AB  - Human adenosine deaminase (ADA) cDNA was randomly mutagenized in vitro and
      bacterial transformants were selected for resistance to the potent enzyme
      inhibitor, pentostatin (dCF). Cells transformed with mutant plasmids dCF-R2 and
      dCF-R6 were able to grow in the presence of 10(-6) M dCF, whereas 10(-11) M dCF
      blocked growth of cells complemented with wild-type ADA. DNA sequence analysis
      revealed double G/A conversions mutating Lys11 and Gln255 in dCF-R2, and Gly 31
      and Glu 99 in dCF-R6, to different amino acids. Located far from the enzyme
      active site, these substitutions did not greatly affect the Km or Ki of the
      enzyme but were predicted to destabilize interactions within the enzyme
      structure. Mutants such as these may be useful to analysis of the stereology of
      inhibitor binding to ADA and toxicity of dCF.

PMID- 7733908
TI  - Role of lipid peroxidation in electroporation-induced cell permeability.
AB  - Erythroleukemia K562 cells and lentil (Lens culinaris) root protoplasts have been
      subjected to pore-forming electric fields suitable for transfection experiments.
      Evidence is presented that the amount of hydroperoxides formed in cell membranes
      of both cell-types is a function of field strength applied. On the other hand,
      the electroporation-induced lipid peroxidation paralleled the enhancement of
      membrane permeability and was associated with greater membrane fluidity. The
      membrane hydroperoxides formed upon electric shock enhanced cell luminescence,
      and lipoxygenase activity appeared to be involved in the process. Electroporation
      of prokaryotic cells of Escherichia coli also enhanced light emission, which was
      higher in lipoxygenase-expressing clones.

PMID- 7733909
TI  - Definition of an interface implicated in gelsolin binding to the sides of actin
      filaments.
AB  - Whereas the interaction of the N-terminal domain of gelsolin with monomeric actin
      is well known, the location of domains 2-3 interacting with the actin filament
      during the severing process remains uncertain. In this study we define an
      interface that supports binding of gelsolin domain 2 along the filament axis.
      Using specific antibodies and actin peptides, this interface was restricted to
      two adjacent segments: 1-10 and 18-28 in the N-terminal part of actin sequence.

PMID- 7733910
TI  - Effects of recombinant human osteogenic protein-1 on the differentiation of
      osteoclast-like cells and bone resorption.
AB  - Recombinant human OP-1 stimulated the formation of tartrate-resistant acid
      phosphatase (TRAP)-positive multinucleated cells (MNCs) significantly and in a
      dose-dependent manner in rat bone marrow cell culture. Newly formed MNCs either
      induced by hOP-1 alone or with 1,25(OH)2D3 were also positive for vitronectin
      receptor and carbonic anhydrase II. Moreover, OP-1 markedly increased the
      capacity of 1,25(OH)2D3 to induce osteoclast-like cell formation and bone
      resorption in bone marrow cultures. 25 pg/ml of calcitonin significantly
      inhibited both OP-1- and vitamin D3-induced TRAP-positive MNC-formation in marrow
      cultures, indicating that in both cases the MNC formation was calcitonin
      sensitive. OP-1 at 5-100 ng/ml did not have any significant effect on bone
      resorption as studied by pit formation assay. These studies that OP-1 in concert
      with 1,25(OH)2D3 could have an important role in bone remodeling by exhibiting
      its effects not only on osteoblast growth and differentiation but also on the
      recruitment of osteoclasts.

PMID- 7733911
TI  - Efficient gene delivery with neutral complexes of lipospermine and thiol-reactive
      phospholipids.
AB  - The presence of thiol-reactive phospholipid derivatives, such as N-4-(p
      maleimidophenyl)butyryl) dipalmitoylphosphatidylethanolamine (MPB-DPPE), in
      electrically neutral lipospermine/DNA particles results in more than a 100-fold
      increased transfection efficiency of human hepatoma HepG2 cells and murine 3T3
      fibroblasts. These effects could be ascribed to the presence of thiol-reactive
      functions, such as maleimide, bromoacetamide and dithiopyridyl linkage, on the
      transfecting particles. We propose that such particles react with thiol groups
      present at the surface of the cells, leading to their covalent anchoring, a
      process that is probably followed by an endocytosis of the complex.

PMID- 7733912
TI  - Quantal release of calcium in permeabilized A7r5 cells is not caused by intrinsic
      inactivation of the inositol trisphosphate receptor.
AB  - Since the role of intrinsic inactivation of the receptor for inositol 1,4,5
      trisphosphate (InsP3) in the phenomenon of quantal release of Ca2+ is still a
      point of debate, we investigated whether inactivation of the InsP3 receptor can
      be responsible for quantal release in permeabilized A7r5 cells. A crucial
      experiment was that a second challenge of the cells with a low dose of InsP3,
      after washing out the first challenge, was unable to produce a renewed phasic
      response under conditions where the Ca2+ pumps were blocked. A new phasic
      response was however obtained with either addition of a higher dose of InsP3 or
      after allowing the refilling of the Ca2+ stores. We conclude therefore that
      quantal Ca2+ release in A7r5 cells is not due to InsP3 receptor inactivation.

PMID- 7733913
TI  - Identification of triadin and of histidine-rich Ca(2+)-binding protein as
      substrates of 60 kDa calmodulin-dependent protein kinase in junctional terminal
      cisternae of sarcoplasmic reticulum of rabbit fast muscle.
AB  - The endogenous calmodulin-protein kinase system of sarcoplasmic reticulum
      terminal cisternae of rabbit fast-twitch muscle was studied. Investigation of a
      single Ca(2+)-channel in terminal cisternae fused to planar lipid bilayers
      demonstrated that the endogenous kinase inhibits the channel, although it
      remained unclear whether the phosphorylation sites are on the channel protein or
      on other junctional sarcoplasmic reticulum specific proteins [Hain et al., (1994)
      Biophys. J. 67, 1823-1833]. Our results, which show that two junctional
      sarcoplasmic reticulum specific proteins, i.e., triadin and histidine-rich Ca(2+)
      binding protein, but not the ryanodine receptor/Ca(2+)-channel protein, are
      phosphorylated by membrane-bound 60 kDa protein kinase, seem to be able to
      resolve this ambiguity. Furthermore, such a probably specific protein isoform of
      calmodulin-protein kinase, by its substrate specificity and exposure to the
      cytoplasmic side of terminal cisternae at the junctional membrane domain and
      based on protease sensitivity, also seems to possess some of the potential
      requirements for a regulatory role in the functional state of the Ca(2+)-channel.

PMID- 7733914
TI  - Evidence for the ligand-independent activation of the AH receptor.
AB  - Benzimidazole derivatives are potent inducers of CYP1A1 in rabbit and human
      hepatocytes, but apparently do not bind the AH receptor. To resolve this
      paradoxical behaviour, studies have been concerned with the question of whether
      an alternative ligand-independent mechanism could explain the activation of the
      AH receptor. From experiments in cultured rabbit hepatocytes we show that
      benzimidazoles bind early and transiently to an unknown protein. Moreover, they
      are able to deplete the AHR in a time- and dose-dependent manner. In contrast,
      benzimidazoles are unable to induce CYP1A1 mRNA in mouse hepa-1 cells and to
      deplete the high-affinity AHR form from these cells. Taken together these data
      suggest that a signal transduction pathway, similar to that involved in the
      ligand-independent activation of steroid receptors, could only activate the low
      affinity forms of AHR as those existing in rabbit and human cells.

PMID- 7733915
TI  - ETB-mediated regulation of extracellular levels of endothelin-1 in cultured human
      endothelial cells.
AB  - Our previous report suggests the important role that ETB receptors play in the
      clearance of circulating endothelin (ET)-1. The present study confirmed this
      finding by measuring the extracellular levels of immunoreactive (ir) ET-1 and
      intracellular contents of prepro (pp) ET-1 mRNA in the presence and absence of
      ETA- and ETB-selective antagonists (i.e., BQ-123 and BQ-788, respectively) in
      cultured human umbilical vein endothelial cells (HUVECs). ET-1 was secreted into
      the culture medium of HUVECs in a time-dependent manner with a plateau reached
      after incubation for more than 36 hr. In the presence of 10 microM BQ-788, the
      irET-1 level was enhanced significantly (i.e., up to 180% of control at 48 hr)
      whereas BQ-123 had no such effect. Specific binding of [125I]ET-1 to HUVECs was
      inhibited strongly by BQ-788 (IC50 = 2.4 nM) but very weakly by BQ-123 (IC50 =
      1.4 microM), indicating that BQ-788 has a potent affinity for ETB receptors in
      HUVECs. The expression of ppET-1 mRNA was not changed by BQ-788. Extracellular
      levels of ET-1 decreased gradually after cellular treatment with cycloheximide.
      This decrease was significantly inhibited by BQ-788 but not by BQ-123 and was non
      existent when the cells were incubated at 4 degrees C (where internalization of
      the receptor protein is not likely). In conclusion, HUVECs secrete ET-1 which, in
      turn, is internalized after binding to ETB receptors on HUVECs.

PMID- 7733916
TI  - Cytosolic nucleoside diphosphate kinase associated with the translation apparatus
      may provide GTP for protein synthesis.
AB  - Elongation of nascent polypeptides in a Dictyostelium discoideum in vitro
      translation system did not require the addition of ATP and GTP when creatine
      phosphate and creatine phosphokinase were present. However, depletion of the
      exogenous energy supply completely abolished incorporation of amino acids.
      Addition of dTTP, a nucleoside triphosphate that can be utilized by nucleoside
      diphosphate kinase (NDP kinase) to phosphorylate endogenous ADP and GDP,
      partially restored protein synthesis. Dictyostelium ribosomes were found to
      contain NDP kinase activity that could not be released by 1 M KCl. Thermal
      denaturation studies, specific inhibition with antibodies, and Western blotting
      identify the activity as cytosolic NDP kinase. These data support the idea that
      GTP can be fed into the translation machinery efficiently by NDP kinase
      associated with active ribosomes.

PMID- 7733917
TI  - Selection and characterization of verapamil-resistant multidrug resistant cells.
AB  - Multidrug resistant cells may become acutely sensitive to the calcium channel
      blocker verapamil, in spite of the fact that its accumulation by these cells is
      negligible. We selected verapamil-resistant mutants from multidrug resistant
      Chinese hamster ovary cells. Levels of P-glycoprotein expression and cross
      resistance profiles remained unaltered in the verapamil-resistant multidrug
      resistant cells. As well, a photoactive verapamil analog specifically bound to P
      glycoprotein in these cells. We had previously used a photoactive anthracycline
      to show that calcium antagonists and several anticancer drugs bind to P
      glycoprotein at overlapping or interacting sites. Verapamil and its analogues no
      longer inhibit the binding of either anticancer drugs or calcium channel blockers
      to P-glycoprotein. Sequencing of P-glycoprotein revealed that no change had
      occurred in the coding sequence as a result of the selection procedure.

PMID- 7733918
TI  - Pharmacological differences between rat and human endothelin B receptors.
AB  - Cloned rat and human endothelin-B receptors (ETBR) were utilized to determine if
      there are significant pharmacological differences between highly homologous ETBR
      from different species. Recombinant rat and human ETBR were expressed in CHO-K1
      cells, and radioligand binding studies were carried out with [125I]-ET-3 to
      determine the affinities of various ET receptor agonists and antagonists for rat
      and human ETBR. These receptors had similar affinities for a number of ETBR
      agonists (ET-1, ET-3, S6C, BQ 3020) and antagonists (Ro 47-0203, PD 142893).
      However, several peptide (PD 147452, PD 151583, BQ 788) and non-peptide (PD
      156707, SB 209670) antagonists had different affinities for rat and human ETBR,
      with differences in Ki values between species ranging from 4.1- to 53.4-fold. The
      ETBR-selective agonist IRL 1620 also had a 5.7-fold higher affinity for rat ETBR
      than human ETBR. Thus despite their high degree of homology, rat and human ETBR
      show significant pharmacological differences with respect to both antagonist and
      agonist binding.

PMID- 7733919
TI  - Association of neurotrophin-3 gene variant with severe forms of schizophrenia.
AB  - The recent possible neurodevelopmental etiology of schizophrenia makes
      neurotrophin-3 (NT-3) gene an interesting candidate locus for molecular study of
      schizophrenia. We searched DNA variants through the coding region and the AP-1
      binding site of the NT-3 gene, and found three variants. One is a missense
      mutation, Gly-63-->Glu-63 (GGG-->GAG), and the others are silent mutations. None
      of them have been associated with schizophrenia. However, a significant
      difference was found in the distribution of the variant, Gly-63-->Glu-63, between
      61 patients and 101 controls, when the patients were restricted to severe cases
      based on the neurodevelopmental perspective. Individuals homozygous or
      heterozygous for the allele Glu-63 had a 2.595-fold increased risk of severe
      forms of schizophrenia.

PMID- 7733920
TI  - NOC, a nitric-oxide-releasing compound, induces dose dependent apoptosis in
      macrophages.
AB  - The ability of exogenous nitric oxide (NO) to induce apoptosis in macrophages was
      analyzed using NOC, a NO-releasing compound, as a source of NO. Exogenous NO was
      shown to induce apoptosis in a dose dependent manner. Quantitative analysis
      revealed that the amount of NO required to induce apoptosis in more than half of
      macrophages exposed was 100 times larger than that for endogenous NO-induced
      apoptosis. NOC proved to be a convenient and useful tool for investigation of
      apoptosis related to NO.

PMID- 7733921
TI  - Genes up-regulated in hypertrophied ventricle.
AB  - We isolated 8 genes whose expression is modulated during cardiac development. The
      expressions of 6 of these eight genes were modulated during the development of
      cardiac hypertrophy and/or during the transition to heart failure. In particular,
      the expression levels of the pro alpha-1 collagen, tissue type II
      transglutaminase, and vimentin genes were markedly increased during the
      transition to heart failure. Up-regulation of the pro alpha-1 collagen and
      vimentin genes may reflect activation of interstitial cells during the transition
      to heart failure. Up-regulation of the tissue type II transglutaminase gene
      during the transition to heart failure is intriguing, since this enzyme has been
      suggested to be involved in the activation of latent TGF-beta.

PMID- 7733922
TI  - cDNA cloning of a novel rat brain cytochrome P450 belonging to the CYP2D
      subfamily.
AB  - Two cDNA clones designated 2d-29 and 2d-35 encoding a novel P450 belonging to the
      P450 2D subfamily were isolated from control and imipramine-treated rat brain
      libraries, respectively. cDNA 2d-29 and 2d-35 contained 1786 and 2754 bp
      nucleotides each. Although their 5'- and 3'-untranslated sequences were different
      from each other, their open reading frames were identical, encoding a protein
      which had 5 substitutions of amino acids in the C-terminal region compared with
      P450 2D4. Northern blot analysis showed that the expression levels of 2d-29 and
      2d-35 in the brain were lower than that of P450 2D4 in the liver. However, it is
      noteworthy that the expression of 2d-35 was not detected in the liver but in the
      brain. These results suggest that a novel P450 is expressed in the brain under
      different regulation.

PMID- 7733923
TI  - Human T helper cell epitopes overlap B cell and putative cytotoxic T cell
      epitopes in the E2 protein of human papillomavirus type 16.
AB  - Activation of T helper cells is a prerequisite for the function of cytotoxic T
      lymphocytes (CTL) and the maturation of the B cell response. Because epitopes
      recognized by each of these cells may overlap, we scanned the E2 protein of human
      papillomavirus (HPV) type 16 to identify the T helper cell epitopes. Four major T
      helper cell epitopes (mapping between aa:s 11-25, 141-155, 191-205 & 231-245) and
      adjacent human B cell epitopes were found. The first peptide-defined epitope
      (RLNV) 11CQDKILTHYENDSTD25 overlapped five putative HLA-I (A1, A2, A0205, A3 &
      A11) binding motifs (CQDKILTHY, RLNVCQDKI, NVCQDKIL, RLNVCQDK & RLNVCQDK). This
      epitope is also part of an N-terminal alpha-helix which may form four HLA-II
      (DR2, DR4, DR7 & DR8) specific agretopes for structures recognizable by the T
      cell receptor (e.g. KILT). The second epitope 141EEASVTVVEGOVDYY155 (GLYY)
      overlapped the putative HLA-A1 & HLA-Bw37 binding motifs (VVEGQVDYY/QVDYYGLYY and
      EEASVTVV), and two HLA-II (DR1 & DR3) specific agretopes. The third and fourth
      epitopes were not associated with more than one putative CTL epitope each. Only
      the first epitope shared considerable aa-homology with corresponding regions of
      other genital HPV types.

PMID- 7733924
TI  - Occurrence of inosine kinase as a distinct enzyme in Spirulina platensis.
AB  - Among a series of purine nucleosides, inosine was found to be phosphorylated at
      the highest rate by crude extracts of the cyanobacterium Spirulina platensis. The
      inosine phosphorylating activity could be separated from hypoxanthine-guanine
      phosphoribosyl transferase. This result shows that IMP formation may occur via
      the direct phosphorylation of inosine at its 5'-position, rather than via inosine
      phosphorolysis, followed by hypoxanthine phosphoribosylation, and provides
      unequivocal evidence for the occurrence of inosine kinase in nature.

PMID- 7733925
TI  - The sequence and genomic organization of the human type 2 angiotensin II
      receptor.
AB  - A human genomic DNA library was screened utilizing a human angiotensin II type 2
      receptor (hAT2R) cDNA as a probe. Several positive clones were isolated and
      characterized. A comparison of the hAT2R cDNA sequence with the hAT2R genomic
      clone sequence suggests that the hAT2R gene is composed of three exons and spans
      at least 5 kb. Exons 1 and 2 encode for 5' untranslated mRNA sequence and exon 3
      harbors the entire uninterrupted open reading frame of the hAT2R. Sequence
      analysis of the 5'-flanking region of the hAT2R gene demonstrates that it
      contains the typical sequence motifs found in many eukaryotic promoters.
      Interestingly, however, this promoter region also includes an interferon
      consensus sequence binding protein site (ICSBP) and a putative embryonal, long
      terminal repeat binding protein (ELP) site. The presence of these novel putative
      transcription factor binding sites suggests that this gene may be regulated in a
      unique manner.

PMID- 7733926
TI  - Complementary DNA cloning of a mu-opioid receptor from rat peritoneal
      macrophages.
AB  - Treatment with opioid agonists in vitro and in vivo has been shown to affect the
      function of the immune system. Several investigators have suggested that immune
      cells may express opioid receptors, but it had been very difficult to demonstrate
      their presence on these cells by direct binding assays. Our earlier studies have
      shown that macrophage progenitor cells are highly sensitive to morphine treatment
      in vitro and in vivo. In the current investigation, we determined, unequivocally,
      the expression of mu-opioid receptor related transcripts in rat peritoneal
      macrophages by reverse transcriptase-polymerase chain reaction (RT-PCR) studies.
      In order to further characterize the transcript, the RT-PCR product was cloned
      and sequenced. The sequence analyses indicate that the transcripts from rat
      peritoneal macrophages are identical to those for the mu-opioid receptor
      described in the rat brain. To further confirm the presence of mu-opioid
      receptors, immunoreactivity to an antiserum raised against the carboxyl terminal
      fifteen amino acid residues of the mu-opioid receptor was determined. These
      studies show for the first time that rat peritoneal macrophages express a mu
      opioid receptor.

PMID- 7733927
TI  - Synthetic lipopeptides activate nucleoside diphosphate kinase in HL-60 membranes.
AB  - We have put forward the hypothesis that lipopeptides (LPs) activate GTP
      hydrolysis by Gi-proteins in HL-60 membranes via activation of nucleoside
      diphosphate kinase (NDPK) as does mastoparan (MP). Therefore, we compared the
      effects of LPs and MP on NDPK- and GTPase activation in HL-60 membranes. In
      native membranes, LPs effectively activated GTP hydrolysis and moderately
      activated GTP formation. In solubilized membranes, the effect of LPs on GTP
      formation was enhanced whereas the one on GTP hydrolysis was abolished. The NDPK
      substrate GDP enhanced the relative stimulatory effect of LPs and MP on GTP
      hydrolysis in HL-60 membranes in the absence of a NTP-regenerating system. A NTP
      regenerating system abrogated the potentiating effect of GDP on MP-action,
      whereas the effect on LP-stimulated GTP-hydrolysis was enhanced. Our data show
      that LPs activate NDPK in HL-60 membranes and that this activation may account
      for their G-protein-stimulatory activity. Membrane solubilization may impair the
      transfer of GTP from NDPK to Gi-protein alpha-subunits and subsequent GTP
      hydrolysis, whereas GTP formation remains intact, augmenting the effect of LPs on
      the kinase. Finally, LP- and MP-induced NDPK activation may involve different
      pools of GDP.

PMID- 7733928
TI  - iyk, a novel intracellular protein tyrosine kinase differentially expressed in
      the mouse mammary gland and intestine.
AB  - Using a polymerase chain reaction based cloning strategy and conventional cDNA
      library screening we have characterized a novel intracellular protein tyrosine
      kinase from mouse mammary tissue. The gene encodes a protein with structural
      characteristics reminiscent of the src family of protein tyrosine kinases, a
      partial myristylation signal with glycine in position +2, SH3 and SH2 domains
      followed by a C-terminal tyrosine kinase domain. Interestingly, a potential
      bipartite nuclear localizing signal is located within the SH2 domain. A data base
      search revealed the highest homology to the human frk/rak gene. Northern blot
      analysis of mammary gland development indicated preferential epithelial
      expression in resting mammary glands and up-regulation in mammary tumours.
      Expression in organs was highest in the intestinal tract and was confined to the
      small intestine. We have named this gene iyk, (intestine tyrosine kinase),
      reflecting its pattern of expression.

PMID- 7733929
TI  - Calreticulin--the potential autoantigen in celiac disease.
AB  - Monoclonal antibodies to gliadin were recently found to cross-react with epitopes
      on rat enterocytes. Two molecules of mol. mass 62 and 66 kDa were isolated from
      enterocyte lysates by affinity chromatography using antigliadin monoclonal
      antibodies. The N-terminal amino acid sequence of the 62-kDa protein was
      determined to be XXXIYFKEQFLD. This amino acid sequence corresponds to amino acid
      sequence of rat calreticulin. The presence of calreticulin in enterocyte lysates
      was further confirmed using anticalreticulin serum. Anticalreticulin serum was
      also used to investigate the reactivity of isolated rat calreticulin. To analyze
      whether gliadin and calreticulin share similar epitopes recognized by
      anticalreticulin antibodies, synthetic dodecapeptides derived from the amino acid
      sequence of alpha gliadin were used in competitive ELISA assay. Two gliadin
      peptides, QEQVPLVQQQQF and YQLLQELCCQHL, were found to inhibit the binding of
      rabbit anti-rat calreticulin sera to rat calreticulin. The significant
      correlation was detected between IgA anticalreticulin and antigliadin antibodies
      (r = 0.827; P < 0.001) in celiac patients.

PMID- 7733930
TI  - Sequence and tissue distribution of a candidate G-coupled receptor cloned from
      rat hypothalamus.
AB  - We have used RT-PCR with degenerate transmembrane primers to clone members of the
      G-coupled protein receptor family from rat hypothalamic suprachiasmatic nuclei.
      We report here a novel clone, UHR-1, which encodes a candidate receptor that is
      most similar to the neuropeptide receptor family, including the tachykinins,
      somatostatins, and opioids. Message for this putative receptor is expressed in
      several brain regions, with the highest levels in pituitary, cerebellum, and
      hypothalamus. No message was detected in peripheral tissues. Southern blot
      analysis suggests that UHR-1 is likely a member of a multigene family. The
      natural ligand for this novel receptor is unknown, but based on sequence homology
      and structural features is likely to be a peptide.

PMID- 7733931
TI  - mRNA expression of two transmembrane protein tyrosine phosphatases is modulated
      by growth factors and growth arrest in 3T3 fibroblasts.
AB  - Changes in mRNA expression are physiological regulatory mechanisms and frequently
      deliver important information regarding functions of corresponding gene products.
      We investigated changes of abundantly expressed mRNAs of two transmembrane
      protein tyrosine phosphatases, LRP (leukocyte common antigen-related phosphatase)
      and mRPTP-sigma. The LRP mRNA expression was modulated by platelet derived growth
      factor (PDGF) treatment and seems to be regulated by PDGF receptor kinase. The
      expression of mRPTP-sigma mRNA was low in actively cycling cells, like those in
      the exponential phase of growth or those treated with different growth factors.
      In cells whose growth was arrested by contact inhibition at high cell density or
      by serum starvation at low cell density mRPTP-sigma mRNA level increased. The
      possible implications of these mRNA expression patterns are discussed.

PMID- 7733932
TI  - Binding of pleckstrin homology domains to WD40/beta-transducin repeat containing
      segments of the protein product of the Lis-1 gene.
AB  - In previous experiments we demonstrated an interaction between certain pleckstrin
      homology (PH) domains and regions containing the so-called WD40 (or beta
      transducin) repeats of the beta subunit of trimeric G-proteins (G beta), a
      finding we here extend to the PH domains of the src-related tyrosine kinase
      TecIIa and the GTPase dynamin. To examine the possibility that WD40 repeats in
      molecules other than G beta might also bind PH domains we examined PAFAH-45, the
      protein product of the Lis-1 gene, which contains 7 WD40 repeats. We found that
      1) Purified PAFAH-45 binds PH domain constructs in vitro. 2) Protein constructs
      expressing all 7 WD40 repeats of PAFAH-45 but lacking the N-terminal non WD40
      region also bind PH domains of beta-adrenergic receptor kinase, beta-spectrin,
      TecIIa and dynamin but with a differing hierarchy of affinities than that seen
      with G beta. 3). PAFAH-45 WD40 repeats will reduce the binding of PH domains to
      brain G beta and brain G beta gamma will reduce the binding of PH domains to
      PAFAH-45. These data support the hypothesis that PH domain/WD40 interactions are
      involved in a wide variety of important protein/protein interactions.

PMID- 7733933
TI  - Cloning and promoter mapping of mouse kappa opioid receptor gene.
AB  - We have isolated mouse kappa opioid receptor (KOR) genomic clones containing the
      complete 5'-untranslated region, a portion of the 3'-untranslated region, and its
      coding region. The mouse KOR gene spans at least 16 kb and contains at least 4
      exons. Exon I encodes the major portion of 5'-untranslated sequence and
      transcription initiation is determined, by primer extension experiments, to
      reside at 3 major sites, located at 334, 340, and 716 nucleotides upstream from
      the translation initiation codon. No typical TATA or CAAT boxes can be identified
      within an approximately 1-kb upstream region. Exon II contains 271 nucleotides,
      including 14 nucleotides of 5'-untranslated sequence. Exon III contains 353
      nucleotides and exon IV begins at amino acid position #204 and encodes the rest
      of the 3'-end sequence of the cloned cDNA. Based upon Northern blot analysis, KOR
      transcript is estimated to be approximately 6 kb in length.

PMID- 7733934
TI  - Distinct patterns of cyclin D1 regulation in models of liver regeneration and
      human liver.
AB  - The expression of cyclin D1 and associated cdks was examined in models of liver
      regeneration and human liver specimens. In mouse liver after 70% partial
      hepatectomy, there was > 20-fold induction of cyclin D1 mRNA and protein,
      beginning prior to peak DNA synthesis. In normal rat liver, basal levels of
      cyclin D1 protein were significantly higher than in the mouse. After hepatectomy
      in the rat, cyclin D1 mRNA was induced 6- to 10-fold, while the protein levels
      changed < 2-fold and did not parallel changes in the mRNA. Cyclin D1 protein was
      detected in freshly isolated rat hepatocytes, but this diminished within 6 hours
      in culture. After growth stimulation with HGF, cyclin D1 mRNA was induced 3- to 5
      fold and its protein > 20-fold in rat hepatocytes. Immunoprecipitation of cyclin
      D1 demonstrated its association with cdk4 but not cdk5 in regenerating liver. In
      human liver biopsy specimens, cyclin D1 protein was detectable in normal liver
      and induced 2- to 10-fold in mitotically active liver following transplantation.
      These results suggest that the regulation of cyclin D1 protein in human liver may
      more closely parallel the mouse than the rat hepatectomy model. Furthermore,
      cyclin expression in primary cells in culture may differ significantly from that
      observed in vivo.

PMID- 7733935
TI  - A new mitochondrial DNA mutation associated with non-insulin-dependent diabetes
      mellitus.
AB  - Mitochondria play an important role in glucose-induced insulin secretion in
      pancreatic beta cells. We therefore examined whether patients with NIDDM exhibit
      genetic variability in mitochondrial DNA (mtDNA), a candidate gene for NIDDM. We
      sequenced mtDNA in the region encoding tRNALeu and the adjacent region in several
      diabetic patients with clinical features suggesting mitochondrial DNA mutations.
      We found a new point mutation at position 3316 that leads to an amino acid change
      in the ND-1 protein. The frequency of the mutation was screened with PCR-RFLP in
      295 NIDDM patients and 406 controls. We found ten NIDDM patients (3.4%) harbored
      the mutation. Although 4 control subjects had the mutation, the frequency was
      significantly higher in the NIDDM patients than in the control subjects (p =
      0.02). These results suggest that the 3316 mutation is associated with NIDDM.

PMID- 7733936
TI  - The protein kinase C inhibitor, bisindolylmaleimide, inhibits the TPA-induced but
      not the TNF-induced increase in LLC-PK1 transepithelial permeability.
AB  - The transepithelial paracellular permeability of an epithelium formed by LLC-PK1
      cells increases upon activation of protein kinase C (PKC) by the phorbol ester
      tumor promoter, TPA, or in response to the cytokine tumor necrosis factor-alpha
      (TNF). Until recently, however, we have not been able to inhibit the permeability
      effects of TPA or TNF using any of the currently available serine-threonine
      kinase inhibitors. In this study we report the treatment of epithelial cell
      sheets with the selective PKC inhibitor bisindolylmaleimide, GF109203X,
      completely prevents the TPA-induced but not the TNF-alpha induced increase in
      tight junction permeability. While PKC-alpha still translocates from the cytosol
      to the membrane of TPA-stimulated epithelial cells overall PKC activity in the
      membrane fraction is markedly reduced in the presence of GFX.

PMID- 7733937
TI  - Expression of VL30 vectors in human cells that are targets for gene therapy.
AB  - Novel vectors made from mouse VL30 retrotransposons were tested in cell types
      that are targets for gene therapy, including normal human cells (skeletal muscle
      epithelium, bronchial epithelium, mammary epithelium), Epstein-Barr virus
      transformed peripheral blood lymphocytes (PBLs), and various tumor cell lines.
      The long terminal repeat (LTR) transcriptional promoter, derived from the
      retroelement NVL-3, expressed abundant mRNA containing the bacterial neomycin
      resistance gene (neo) in all cell types tested. The amounts of neo RNA detected
      on RNA blots from normal vs. transformed cells were similar, although relatively
      less RNA was expressed in PBLs than in other cell types. Vector RNA expression in
      PBLs persisted during six months of continuous culture. Transcription was
      regulated by fibroblast growth factor (bFGF) and insulin, with the effects of
      each being cell-type-dependent. Thus, VL30 vectors introduced and expressed
      transgenes at significant levels in a number of cell types that are of interest
      for human gene therapy of metabolic and neoplastic diseases.

PMID- 7733938
TI  - The Thermoplasma acidophilum rpl15 gene encodes a homologue of eukaryotic
      ribosomal proteins L15/YL10.
AB  - A gene has been cloned from the archaebacterium, Thermoplasma acidophilum, which,
      on the basis of the deduced amino acid sequence, encodes a homologue of the
      eukaryotic large subunit ribosomal proteins, L15/YL10. This gene, rpl15, was
      identified as an open reading frame (ORF) located 2.3 kb upstream of the gene
      encoding the alpha-subunit of the T. acidophilum proteasome. The putative
      translation product of rpl15 (RPL15) contains 197 amino acid residues, with a
      M(r) of 22,928 and a basic pI of 11.59. The RPL15 amino acid sequence shows
      significant similarity (> 35% identity) to the L15/YL10 proteins of various
      eukaryotes.

PMID- 7733939
TI  - GYIRFamide: a novel FMRFamide-related peptide (FaRP) from the triclad
      turbellarian, Dugesia tigrina.
AB  - Modern phylogenetic schemes propose a free-living turbellarian-like organism as
      the ancestor of all Bilateria, including chordates. While neuropeptides are now
      known to be of ancient origin within the nervous systems of invertebrates, the
      neuropeptides of turbellarians remain virtually unexplored. Here we report the
      primary structure of an FMRFamide-related pentapeptide, Gly-Tyr-Ile-Arg-Phe amide
      (GYIRFamide), isolated from an acidified ethanolic extract of the aquatic triclad
      turbellarian, Dugesia tigrina. Previously, we reported the primary structure,
      RYIRFamide, from the New Zealand terrestrial turbellarian, Artioposthia
      triangulata, widely regarded as a most atypical species. However, the present
      data implies a high degree of primary structural conservation between the
      FMRFamide-related peptides of both species despite the zoogeographical isolation
      of the New Zealand form for several hundred million years. In addition, while
      authentic FMRFamide itself has been identified in many molluscs and a few
      annelids, the current data would suggest that turbellarian analogues are
      typically pentapeptides with an X-Y-I-R-Famide motif. A protein/peptide database
      search revealed that the sequence GYIRF is contained within the primary structure
      of several bacterial Ni/Fe hydrogenase B-type cytochrome subunits and several
      proliferating cell nuclear antigens (cyclins) from plants.

PMID- 7733940
TI  - Evidence that in situ generated reactive oxygen species act as a potent stage I
      tumor promoter in mouse skin.
AB  - A body of indirect evidence has suggested the involvement of reactive oxygen
      species (ROS) in tumor promotion. However, direct evidence for the involvement of
      in situ generated ROS in tumor promotion is lacking at present. This study
      provides the first in situ evidence for the involvement of ROS in stage I tumor
      promotion. Earlier we have shown that parenteral administration of Photofrin-II
      (a mixture of porphyrins) to mice followed by their exposure to visible light
      generates ROS. In this study we further provide E.S.R. spectral evidence that
      both O2.- and .OH radicals are generated during tissue photosensitization. The
      free radicals/ROS generation is followed by the development of cutaneous
      inflammation which is maximum at six hours after photosensitization and develops
      in a dose dependent manner. The epidermal myeloperoxidase activity which
      represents neutrophil infiltration is also increased more than 160% of the
      control value. The histopathology of skin tissues of 7,12 dimethyl
      benz(a)anthracene initiated mice receiving multiple treatments of Pf-II and light
      for a period of four weeks indicates pronounced epidermal hyperplasia, glandular
      hyperplasia, dark basal keratinocytes induction characterized by the high uptake
      of the dye and frequent neutrophil infiltrations. Our data indicate that ROS
      generated in situ as a result of porphyrin-mediated cutaneous photosensitization
      results in the development of changes characteristic of stage I tumor promotion
      in murine skin.

PMID- 7733941
TI  - The differentiation-related upregulation of aryl hydrocarbon receptor transcript
      levels is suppressed by retinoic acid.
AB  - The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) binds to
      a specific intracellular receptor protein -the Ah-receptor- which acts as a
      transcription factor. Herein we report on the relative levels of Ah-receptor-mRNA
      and TCDD-induced cytochrome P450 1A1 (Cyp1A1)-mRNA and their modulation by
      retinoic acid in the human keratinocyte cell line HaCaT. Ah-receptor-mRNA was
      already present in proliferating keratinocytes and increased 8-fold in the course
      of differentiation. Addition of 10 nM TCDD did not alter the level of Ah-receptor
      transcripts. In contrast, addition of 1 microM RA maintained the amount of Ah
      receptor-mRNA at the basal level as observed only in proliferating keratinocytes.
      The transcription of Cyp1A1 was dependent on TCDD-treatment and increased
      fivefold in more differentiated cells as compared to proliferating cells.
      Simultaneous addition of retinoic acid revealed an only twofold increase. These
      results indicate that the expression of the AhR is dependent on the state of
      differentiation of keratinocytes and seems to be affected by retinoic acid.

PMID- 7733942
TI  - Species difference in the binding characteristics of RES-701-1: potent endothelin
      ETB receptor-selective antagonist.
AB  - Species-dependency of RES-701-1 (cyclic (Gly1-Asp9)(Gly-Asn-Trp-His-Gly-Thr-Ala
      Pro-Asp-Trp-Phe-Phe- Asn-Tyr-Tyr-Trp)) has been shown using 125I-ET-1 binding to
      membranes from various animal tissues. RES-701-1 selectively inhibited the 125I
      ET-1 binding to ETB receptor from canine, rabbit, porcine, and guinea pig lung
      tissues in a dose-dependent manner with IC50 values of 60 nM, 20, 4 nM and 13 nM,
      respectively. Though RES-701-1 retained selectivity for ETB receptor even at
      higher concentrations, RES-701-1 inhibited the 125I-ET-1 binding to ETB receptor
      from rat lung, heart, and kidney only weakly; IC50 values were calculated to be
      1.2 microM, 0.9 microM and 0.6 microM, respectively. These results suggest that
      RES-701-1 is a potent and specific antagonist for ETB receptor in various species
      of animal, and would be a powerful tool for understanding the physiological roles
      of ETB receptor, but care must be taken in use of RES-701-1 in experiments with
      rat.

PMID- 7733943
TI  - Evidence for the existence of two human CYP2E1 cDNAs using different
      polyadenylation signals.
AB  - We have isolated a cDNA (named P450 A) which is a variant of CYP2E1 presenting
      some differences in the 3' non coding region. Two substitutions and only one
      polyadenylation signal were detected on P450 A compared to CYP2E1 where there are
      two. With the aim of studying the frequency of utilization of these
      polyadenylation signals, probe A and probe J specific for P450 A and CYP2E1,
      respectively, were hybridized on human hepatic and extra-hepatic cDNA samples.
      Results indicated that in all tissues tested only P450 A using the first
      polyadenylation signal was detected. The CYP2E1 cDNA isolated by Song et al could
      be representative of a transcript either rarely represented among the Caucasian
      population, or expressed in a particular individual or ethnic population, or
      rapidly degraded.

PMID- 7733944
TI  - Oxygen stress induces an apoptotic cell death associated with fragmentation of
      mitochondrial genome.
AB  - We have investigated the role of mitochondria on an active cell death, a feature
      of apoptosis, under the oxygen stress. An immortalized human fibroblast cell line
      (rho+) carrying normal mitochondrial genome (mtDNA) underwent an active cell
      death in 95% oxygen; 68% and 84% of the cells died on the 3rd and 4th days,
      respectively. By contrast, its derivative lacking mtDNA (rho 0) exhibited a
      marked resistance to cell death. PCR analyses using 180 primer pairs covering the
      entire regions of the mtDNA revealed extensive fragmentations of the mtDNA; 49
      types of deletions increased up to 187 on the 3rd day. These results indicate
      that mtDNA and its fragmentation are the underlying molecular lesions in a cell
      death pathway induced by the oxygen stress.

PMID- 7733945
TI  - Endogenous peroxynitrite is involved in the inhibition of mitochondrial
      respiration in immuno-stimulated J774.2 macrophages.
AB  - The free radicals nitric oxide (NO) and superoxide (O2-) are known to react to
      form peroxynitrite (ONOO-), a potentially more injurious species. Here we
      compared the inhibitory effects of ONOO- and NO on mitochondrial respiration in
      J774.2 macrophages. In addition, using uric acid, a potent scavenger of ONOO-, we
      investigated the potential involvement of endogenous ONOO- in the inhibitory
      effects of bacterial lipopolysaccharide (LPS) and gamma-interferon (IFN) on
      mitochondrial respiration. The NO donors S-nitroso-N-acetyl-DL-penicillamine
      (SNAP, 1 mM) or diethylamine NONOate (DN, 1 mM) inhibited cellular respiration by
      approximately 30% over 24h. Equimolar amounts of ONOO- caused a more pronounced
      inhibition of cell respiration. There was a synergistic effect between the O2-
      generator pyrogallol (10 microM-1 mM) and the NO donor SNAP (1 mM) in inhibiting
      mitochondrial respiration. The ONOO- scavenger uric acid (UA, 1 mM) did not
      prevent the decrease in viability in response to SNAP, DN or pyrogallol, but
      significantly prevented the decrease in cell viability in response to ONOO-, to
      the combination of SNAP and pyrogallol, and to SIN-1, a compound that
      simultaneously generates NO and O2-. The decrease in mitochondrial respiration in
      response to LPS and IFN was also inhibited by UA as well as by NG-methyl
      arginine, an inhibitor of NOS. Thus, ONOO- is a more potent suppressant of
      mitochondrial respiration than NO and endogenous formation of ONOO- appears to be
      involved in the cytotoxicity associated with immune stimulation.

PMID- 7733946
TI  - A new type of human calcitonin receptor isoform generated by alternative
      splicing.
AB  - There are three isoforms of calcitonin receptors (CTRs). The first type (type 1)
      has 479 amino acids in rat and 482 amino acids in porcine. The second type (type
      2) has a 39 amino acid insertion in the second extracellular domain. The third
      type (type 3) has a 16 amino acid insertion in the first intracellular domain.
      The CTR which has been isolated from a human ovarian carcinoma cell line belongs
      to type 3. Using RT-PCR with primers whose sequences correspond to the human CTR
      cDNA, we analyzed the expression of the CTR transcripts in seven human tumor cell
      lines and surgical specimens. The CTR m-RNA were found in all samples.
      Transcripts which were 48bp shorter than that of the type 3 human CTR were
      detected, but not transcripts of type 2 and type 3. Since the structure of this
      CTR is same as that of the type 1 rat and porcine CTRs, we termed it the human
      type 1 CTR. PCR studies using human genomic DNA as a template revealed that the
      48bp sequence constitutes an exon. These results indicate that the type 1 and the
      type 3 human CTRs are generated by alternative splicing and a majority of human
      CTR transcripts is type 1.

PMID- 7733947
TI  - A novel putative neuropeptide receptor expressed in neural tissue, including
      sensory epithelia.
AB  - We have used a homology based approach to identify G protein-coupled receptors
      preferentially expressed in retinal and taste cells. Rat and bovine sequences
      encoding a novel G protein-coupled receptor have been isolated. Analysis
      indicates that while the protein sequence is most similar to the receptors for
      somatostatin and opiates, it is unlikely to be a subtype of these receptors.
      Northern and RNase protection analysis indicates that the gene is preferentially
      expressed in neural and sensory tissues.

PMID- 7733948
TI  - Galectin-1 modulates human melanoma cell adhesion to laminin.
AB  - Galectins constitute a gene family of beta-galactoside-specific lectins that show
      high homology in their carbohydrate-binding site. They have been postulated to be
      involved in many biological events, but their specific functions are not yet well
      defined. Galectin-1 is a laminin binding protein that recognizes poly-N
      acetyllactosamine chains on this major basement membrane glycoprotein. In this
      study, we analyzed the possibility that galectin-1 could modulate interactions
      between human melanoma cells and laminin. We demonstrated that A375 and A2058
      cell lines express galectin-1 both intracellularly and on the cell surface. In an
      in vitro assay, recombinant galectin-1 increased melanoma cell attachment to
      laminin in a dose-dependent manner. This effect was abolished by lactose. Anti
      galectin-1 inhibited adhesion of melanoma cells to laminin in a dose-dependent
      fashion. However, neither galectin-1 nor anti-galectin-1 antibody affected
      melanoma cell spreading on laminin in vitro. These data indicate that galectin-1
      might participate in melanoma cell adhesion to laminin and therefore could be a
      modulator of invasion and metastasis.

PMID- 7733949
TI  - Induction of apoptosis in HL-60 cells by lithium.
AB  - It has been established that lithium, a preferred drug for the treatment of manic
      depression, affects the growth of HL-60 cells. Concentrations of lithium above 10
      mM were shown to be cytotoxic to these cells. However, the mechanism by which
      lithium induces its cytotoxicity is still obscure. In this study, we examined
      whether programmed cell death was involved in lithium cytotoxicity. Our findings
      show that lithium induced apoptosis in a time- and concentration-dependent
      manner. Morphological features and DNA fragmentation revealed that with 10 mM
      lithium, apoptosis was maximal at 72 hours of treatment. Interestingly, other
      monovalent ions were unable to elicit DNA fragmentation, suggesting that this
      phenomenon is specific for lithium. Cell cycle studies revealed that lithium
      arrested the cells at the G2/M phase.

PMID- 7733950
TI  - Antimicrobial peptides from the skin of a Korean frog, Rana rugosa.

PMID- 7733951
TI  - Expression of kappa opioid receptors in human and monkey lymphocytes.
AB  - mRNA encoding the kappa opioid receptor gene sequence was identified and isolated
      from various human lymphocytic cells: CEM x174 (a hybrid of T and B origin)
      cells, Jurkat-T4 cells, human peripheral blood mononuclear cells (PBMC) and
      purified CD4+ cells. Analyzing the cDNA sequences of RNA transcripts spanning the
      putative second extracellular loop, which has reported dynorphin specificity, and
      the seventh transmembrane domain revealed a 100% and 95% homology in amino acid
      sequence to corresponding kappa opioid receptor sequences in human placenta and
      rat brain, respectively. Expression of a similar kappa opioid receptor sequence
      could be detected in normal monkey PBMC but not in monkey PBMC in which the
      CD4+/CD8+ cell ratio (or CD4+ cell number) was significantly reduced due to
      prolonged SIV infection. These findings suggest that human and monkey lymphocytes
      constitutively express kappa opioid receptor mRNA.

PMID- 7733952
TI  - Plasma membrane fatty-acid-binding protein in human placenta: identification and
      characterization.
AB  - A plasma membrane fatty-acid-binding protein (FABPpm) with a molecular mass of
      approximately 40 kDa has been identified in human placenta. Binding of both [14C]
      oleate and [14C] linoleate to human placental membranes was found to be time and
      temperature dependent. Sulphobromophthalein and alpha-tocopherol did not show
      competition with the [14C] fatty acid binding. These data suggest that the
      binding sites are specific for fatty acids. incubation of the membranes with
      trypsin reduced fatty acid binding activity, indicating that the binding sites
      were protein in nature. A FABPpm was then solubilized from placental membranes
      and purified to electrophoretic homogeneity. The fatty acid binding activity of
      the purified protein was confirmed by autoradioblotting. Polyclonal antiserum
      raised to FABPpm reduced fatty acid binding to placental membrane significantly
      compared with preimmune serum. The pI value and the amino acid composition of the
      protein suggest that the placental FABPpm is different from the previously
      identified hepatic FABPpm.

PMID- 7733953
TI  - Electrochemical studies on nitrite reductase towards a biosensor.
AB  - A c-type hexaheme nitrite reductase (NiR) isolated from nitrate-grown cells of
      Desulfovibrio desulfuricans (Dd) ATCC 27774 catalyses the six-electron reduction
      of nitrite to ammonia. Previous electrochemical studies demonstrated that a
      simple electrocatalytic mechanism can be applied to this system (Moreno, C.,
      Costa, C., Moura, I., LeGall, J., Liu, M. Y., Payne, W. J., Van Dijk, C. and
      Moura, J. J. G. (1992) Eur.J.Biochem. 212, 79-86). Its substrate specificity,
      availability and stability under ambient conditions makes this enzymatic system a
      promising candidate for use in a biosensor device. An electrochemical study of
      gel-immobilized Dd NiR on a glassy carbon electrode revealed both enzymatic
      activity and amperometric response to nitrite. In this study it was observed that
      the catalytic current density is a function of the nitrite concentration in
      solution and follows a characteristic Michaelis-Menten-type substrate dependence.
      Such a biosensor device (NiR-electrode) bears the option to be used for
      analytical determination of nitrite in complex media.

PMID- 7733954
TI  - Nucleotide and primary sequences of a rice endosperm cDNA are extensively
      homologous to elongation factor 1 beta'.
AB  - A rice endosperm cDNA expression library prepared with poly (A+) RNA was screened
      with polyclonal antibodies raised against purified 16 kD globulin. One of the
      three positive antigen producing clones was completely sequenced. This clone was
      composed of 759 bp and contained a single open reading frame encoding 192 amino
      acids. The 3' untranslated region did not include a typical polyadenylation
      signal, AATAAA. The cDNA encodes a protein of molecular weight 21,064 with an
      isoelectric point of 4.3. The amino acid sequence of the rice seed cDNA shows
      extensive homology to elongation factor 1 beta' from several sources, including
      human and Artemia salina. The molecular weight of rice seed EF-1 beta' is smaller
      than the others, and it lacks a conserved phosphorylation site that has been
      implicated in regulating nucleotide exchange activity.

PMID- 7733955
TI  - Calcium signalling initiated by CR1 (CD35) crosslinking is mediated by phagocyte
      Fc gamma receptors in cis.
AB  - We have examined the role of complement receptor type 1 (CR1; CD35) in generating
      intracellular signals in phagocytic cells, particularly human neutrophils. We
      find that crosslinking of CR1 alone fails to result in an increase in
      intracellular ionized calcium [Ca2+]i. However, IgG bound to CR1 is able to
      interact with Fc gamma receptors to stimulate increases in [Ca2+]i. By examining
      signals generated in mixed populations of cells, we determined that calcium
      increases are observed only when CR1 and Fc gamma receptors are engaged on the
      same cell. Functional interactions between complement receptors and receptors for
      immunoglobulin G may promote clearance of pathogenic bacteria and fungi that bind
      limited quantities of complement and IgG.

PMID- 7733956
TI  - Annexin VI is secreted in human bile.
AB  - A calcium-binding protein of 68 kDa was isolated from human bile that
      precipitates upon addition of 5 mM CaCl2. This protein was recognized by an
      immunoaffinity purified anti-annexin VI antibody and it had a similar aminoacid
      composition as annexin VI. Phospholipase A2 activity was inhibited in vitro in a
      dose-dependent manner as reported for annexin VI. It is the first time that an
      annexin secretion is demonstrated in bile.

PMID- 7733957
TI  - Palladium--a new inhibitor of cellulase activities.
AB  - Palladium complexes have been shown to strongly inhibit cellobiohydrolase I (CBH
      I) and endoglucanase II (EG II), two cellulases produced by Trichoderma reesei.
      Also inhibited were total cellulase (Avicelase) and beta-glucosidase (cellobiase)
      activities. The catalytic domain of CBH II, the second most abundant component of
      this cellulase, appeared less susceptible to inhibition by palladium. The
      inhibition was irreversible and could be prevented if histidine, cysteine or
      cystine was added to the enzyme reaction mixture simultaneously with the
      inhibitor. The binding of CBH I to microcrystalline cellulose (Avicel) was
      unaffected by palladium.

PMID- 7733958
TI  - Fatty genotype-induced increase in GLUT4 promoter activity in transfected
      adipocytes: delineation of two fa-responsive regions and glucose effect.
AB  - We have previously shown that adipocytes from genetically obese rats exhibited
      increases in GLUT4 protein and mRNA expressions. In order to elucidate the
      responsible defect we examined here the activity of GLUT4 promoter using
      adipocytes transiently transfected with -2212 + 164 rat GLUT4 gene fragment fused
      to luciferase reporter gene. GLUT4 promoter activity was several-fold higher in
      obese than in lean rat adipocytes (x4 in suckling 16 days old and x6 in weaned 30
      days old rats), demonstrating the implication of transcription factors in the
      fatty genotype effect on GLUT4 expression. 5' deletion analysis of GLUT4 promoter
      allowed us to delineate two regions, -907 to -502 and -151 to -68, critical to
      the genotype effect, suggesting that they harbor fa-response element(s). In lean
      rat adipocytes GLUT4 promoter activity was not affected by the presence of
      glucose in the culture medium. In contrast, in obese rat adipocytes GLUT4
      transcriptional activity was increased 3-fold from 0 to 5mM glucose, the
      concentration required for the full genotype effect, suggesting interactions
      between glucose and fa-dependent GLUT4 transactivator(s).

PMID- 7733959
TI  - The N-terminal half of dystrophin is protected from proteolysis in situ.
AB  - Using a panel of "exon-specific" monoclonal antibodies, we have examined the
      products of degradation of dystrophin by endogenous proteases in post-mortem
      human muscle. Four main sites of dystrophin digestion were identified, all of
      them in the C-terminal half of the molecule. Two of them correspond to "hinges"
      in the central rod region and a third in the C-terminal domain follows the
      dystroglycan binding site. The results support the Koenig and Kunkel model for
      the tertiary structure of dystrophin (J. Biol. Chem. 265 (1990) 4560-4566), but
      suggest that much of the N-terminal half of dystrophin is protected from
      proteolysis, possibly by interaction with the sub-sarcolemmal cytoskeleton.
      Although the results seem inconsistent with an anti-parallel dimer model of
      dystrophin in which hinge 2 and hinge 3 are close together, possible ways of
      reconciling them with such a model are also considered.

PMID- 7733960
TI  - Rapid identification of differentially expressed endothelial cell genes by RNA
      display.
AB  - Endothelial cells line the inside of all blood vessels forming a structurally and
      functionally highly heterogenous population of cells. Here we describe the
      application of the differential RNA display technique to the analysis of the
      heterogeneity of endothelial cells. Multiple fragment cDNAs from quiescent
      resting and from activated migrating endothelial cells were amplified by RT-PCR
      using random 10mer 5' primers and T11XY 3' primers. Labelled amplification
      products were displayed on a sequencing gel. Expression patterns of more than
      5000 bands of the two cell populations were approximately 98% identical. Of the
      differentially expressed bands, 26 fragment cDNAs were reamplified, sequenced,
      and used as probes for Northern blots. Approximately 50% of the analyzed fragment
      cDNAs could be confirmed as being differentially expressed by Northern blot
      analysis. Among the differentially expressed cDNAs was follistatin, which was
      exclusively expressed by migrating and not by quiescent arrested endothelial
      cells. Stimulation by exogenous bFGF, however, induced follistatin expression in
      arrested endothelial cells. These experiments support the use of the differential
      RNA display technique as a rapid cloning strategy for the identification of
      differentially expressed genes and suggest a role of the follistatin/activin
      system in the autocrine control of endothelial cell growth and differentiation.

PMID- 7733961
TI  - Identification in mouse macrophages of a new 4Kb mRNA present in hematopoietic
      tissues, which shares a short nucleotide sequence with erythropoietin mRNA.
AB  - A mRNA of larger size (4 Kb) than that of erythropoietin is found in
      hematopoietic tissues and macrophages after hybridization of Northern blots with
      an EPO cRNA probe. The cross-hybridizing fragment is located in the 3'
      untranslated region of the EPO mRNA. The level of this new mRNA is increased in
      anemic mice, which suggests that it might correspond to a molecule involved in
      erythropoietic regulation.

PMID- 7733962
TI  - Studies with wortmannin suggest a role for phosphatidylinositol 3-kinase in the
      activation of glycogen synthase and mitogen-activated protein kinase by insulin
      in rat adipocytes: comparison of insulin and protein kinase C modulators.
AB  - Wortmannin, a selective inhibitor of phosphatidylinositol 3-kinase (PI3K),
      blocked insulin-induced activation of glycogen synthase (GS) and mitogen
      activated protein kinase (MAPK) in rat adipocytes. These inhibitions were
      relatively specific, as wortmannin did not block GS activation by a protein
      kinase C (PKC) inhibitor, or MAPK activation by phorbol esters. Our findings
      suggest that PI3K is required for the activation of both GS and MAPK in rat
      adipocytes.

PMID- 7733963
TI  - Regulation of ovine beta-lactoglobulin gene expression during the first stage of
      lactogenesis.
AB  - In the lactating mammary gland, expression of the ovine beta-lactoglobulin gene
      correlates with the presence of a strong DNaseI hypersensitive site encompassing
      the promoter region. At this stage of lactogenesis, prolactin is required for
      optimal expression. Using DNaseI as a probe for formation of a transcription
      complex on the beta-lactoglobulin promoter, the temporal pattern of ovine beta
      lactoglobulin expression during pregnancy has been addressed. The appearance of
      nuclease hypersensitivity during pregnancy correlates with rising levels of
      placental lactogen which suggests that this hormone may be the stimulus for
      expression during the first stage of lactogenesis. This raises the possibility
      that a different signalling pathway to that present in the lactation functions
      during pregnancy.

PMID- 7733964
TI  - Transmembrane segments critical for potassium channel function.
AB  - The relative contribution of the transmembrane segments in the alpha-subunit of
      Shaker-type potassium channels was investigated in relation to potassium channel
      function. Starting from a wild-type Kv1.1 channel, four different deletion
      mutants were made, missing respectively transmembrane segments S1 and S2, S2 and
      S3, S1 to S3, and S1 to S4. To ensure the assembly of the different subunits, the
      hydrophylic N-terminal domain was always conserved. The lack of transmembrane
      segments S1 to S4 converts a depolarization-activated WT Kv1.1 channel with
      outward rectification into a hyperpolarization-activated channel with inward
      rectification. In contrast, mutant channels missing transmembrane segments S1 and
      S2, S2 and S3, or S1 to S3 did not reveal functional expression.

PMID- 7733965
TI  - Microfilament assembly is required for anti-IgM dependent MAPK and p90rsk
      activation in human B lymphocytes.
AB  - Mitogen-activated protein kinases (MAPK) are important mediators of signal
      transduction from the cell surface to the nucleus. These MAPK pathways serve
      different receptor-mediated signaling pathways leading to dual phosphorylation on
      serine/threonine and tyrosine residues. The mechanisms linking cytoplasmic MAPK
      activation to later events is still unclear. In this study we demonstrate that
      the microfilament system has an active role in MAPK activation. Cross-linking of
      surface IgM or direct activation of PKC with PMA resulted in time and
      concentration-dependent increases in F-actin content, MAPK (p42erk-2) activation,
      and phosphorylation of p90rsk. Pretreatment of the B cells with cytochalasin D or
      botulinum C2 toxin, microfilament-disrupting agents, prevented the increases in F
      actin content as well as MAPK and p90rsk activation. These data indicate a role
      for the microfilament system in the complex and divergent functions of MAPK.

PMID- 7733966
TI  - Platelet activating factor activates MAPK and increases in intracellular calcium
      via independent pathways in B lymphocytes.
AB  - Platelet activating factor (PAF)-stimulation of human B-lymphoblastoid cells
      results in the activation of microtubule associated protein 2-kinase (MAPK) and
      increases in intracellular calcium. Although increases in intracellular calcium
      induce MAPK activation in these cells, PAF can stimulate MAPK activation in the
      absence of detectable changes in intracellular calcium concentrations ([Ca2+]i).
      Treatment of the LA350 B-lymphoblastoid cell line with either pertussis toxin
      (PT) or cholera toxin (CT) blocked PAF-induced changes in [Ca2+]i. However, only
      PT blocked PAF-induced activation of MAPK as determined by shifts in the mobility
      of MAPK on immunoblots. In support of this finding, only PT but not CT blocked
      PAF-induced phosphorylation and activation of p90rsk, an event thought to be
      distal to MAPK activation. These results suggest that the PAF receptor is
      mediating MAPK activation through pathways separate from those mediating
      increases in intracellular calcium.

PMID- 7733967
TI  - Abnormal gene product identified in Huntington's disease lymphocytes and brain.
AB  - Huntington's disease(HD) is associated with expansion of an unstable CAG repeat.
      Using antibodies against the synthetic peptide corresponding to the sequence of
      HD gene IT15, we have identified the HD gene product in normal lymphocytes as a
      approximately 350kDa protein by immunoblot analysis. Moreover, when a modified
      SDS-PAGE using a low concentration of methylenbisacrylamide was run longer,
      abnormal immunoreactive bands larger than normal ones were found exclusively in
      HD samples. These results demonstrate the existence of the expanded CAG repeat
      gene product and open a possibility that the expanded polyglutamine stretch may
      really participate in the pathological process of the CAG repeat diseases.

PMID- 7733968
TI  - Cloning and expression of a catalytic core bovine brain 6-phosphofructo-2
      kinase/fructose-2,6-bisphosphatase.
AB  - A cDNA encoding the catalytic core of a novel brain 6-phosphofructo-2
      kinase/fructose-2,6-bisphosphatase isoenzyme was isolated from a lambda gt10
      bovine brain library. This brain cDNA begins and ends in an open reading frame
      encoding a peptide of 476 amino acids. This peptide contains both the catalytic
      kinase and bisphosphatase domains and has an overall 65% and 67% indentity with
      the bovine heart and liver isozymes, respectively, whereas the NH2 and COOH
      termini are divergent. An active catalytic core brain bifunctional enzyme was
      expressed in E. coli using a T7 RNA polymerase-based expression system. These
      results support the presence of a distinct gene coding for the protein in bovine
      brain.

PMID- 7733969
TI  - Molecular cloning and sequencing of a guinea pig cytochrome P4502D (CYP2D16):
      high level expression in adrenal microsomes.
AB  - Studies were done to characterize a guinea pig adrenal microsomal P450 that had
      been linked with xenobiotic metabolism in the inner zone of the gland. N-terminal
      amino acid sequencing of the isolated protein revealed homology with members of
      the CYP2D subfamily. A human CYPD2D6 cDNA probe was used to screen a guinea pig
      adrenal cDNA library and a full-length clone was obtained having an open reading
      frame encoding a 500 amino acid protein. The sequence was found to be highly
      homologous with all members of the CYP2D subfamily and was designated CYP2D16.
      The N-terminal sequence of 38 amino acids obtained from the protein
      microsequencing was identical to that deduced from the nucleotide sequence of the
      cloned CYP2D16. Northern blot analysis confirmed that CYP2D16 is expressed at
      high levels in the inner zone of the guinea pig adrenal cortex. The results
      suggest that CYP2D16 may account, at least in part, for the high rates of
      xenobiotic metabolism in the guinea pig adrenal.

PMID- 7733970
TI  - Substrate specificity differences between recombinant rat testes endopeptidase EC
      3.4.24.15 and the native brain enzyme.
AB  - We have characterized and compared the substrate specificity of affinity-purified
      recombinant rat testes endopeptidase EC 3.4.24.15 (EP 24.15) with that reported
      for the isolated brain enzyme. Of the peptides tested, only bradykinin, dynorphin
      A1-8, and neurotensin were efficiently cleaved by the recombinant enzyme (kcat/Km
      = 3.0, 2.8 and 0.5 x 10(5) M-1sec-1, respectively); other peptides considered
      substrates of EP 24.15 (gonadotropin-releasing hormone, substance P, somatostatin
      and angiotensin) were not metabolized. The enzyme was inhibited by metal ion
      chelators and thiol-reactive agents, as well as a specific EP 24.15 inhibitor (N
      [1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate), thus confirming the
      enzyme as a thiol-dependent metalloendopeptidase. The observed discrepancies in
      substrate specificity of the recombinant testicular and the isolated brain
      enzymes may result from tissue-specific forms and/or post-translational
      modifications of EP 24.15.

PMID- 7733971
TI  - Glyceraldehyde 3-phosphate dehydrogenase is an enzyme-crystallin in diurnal
      geckos of the genus Phelsuma.
AB  - Lenses from diurnal geckos, Phelsuma barbouri, Phelsuma madagascariensis grandis
      and Phelsuma serraticauda contain a prominent 37 kDa polypeptide (pi-crystallin)
      that is not present in lenses from the nocturnal geckos, Gekko gekko,
      Hemidactylus garnoti, Tarentola annularis, and Uroplatus henkeli. This protein
      was partially purified from P. serraticauda and was identified as glyceraldehyde
      3-phosphate dehydrogenase (GAPD). The GAPDs, which constitute 14-24% of the lens
      soluble protein in the diurnal species, were highly active. The presence of this
      enzyme in the lenses of diurnal, but not nocturnal, geckos supports the
      hypothesis that the oxido-reductases found as enzyme-crystallins may function in
      providing protection against the increased oxidative stress to which diurnal
      species are exposed. These findings strongly support the concept that the
      recruitment of enzyme-crystallins is a selective response to changes in the
      visual environment.

PMID- 7733972
TI  - Immunohistochemical localization of guanylin in the rat small intestine and
      colon.
AB  - Guanylin is an endogenous mammalian ligand which binds to guanylate cyclase C (GC
      C), the Escherichia coli heat-stable enterotoxin receptor. This interaction
      results in intestinal Cl- and fluid secretion, which is largely, if not
      exclusively, mediated through the cystic fibrosis transmembrane regulator (CFTR).
      Using in situ hybridization, we have previously localized guanylin mRNA to villus
      epithelial cells of the rat small intestine and to superficial epithelial cells
      of the rat colon. In the present study, we demonstrate immunoreactive guanylin in
      a subpopulation of goblet cells in the rat jejunum and ileum. In the colon, there
      was immunostaining of superficial epithelial cells and goblet cells. The
      immunohistochemical localization of guanylin parallels the observed distribution
      of guanylin mRNA. Localization of guanylin in goblet cells leads us to speculate
      that an in vivo function of guanylin regulated, CFTR-mediated Cl- secretion is to
      hydrate intestinal mucin.

PMID- 7733973
TI  - An additional limb can be induced from the flank of the chick embryo by FGF4.
AB  - To elucidate what initiates formation of the limb, we have attempted to induce an
      additional limb from the flank of the chick embryo by infecting retrovirus or
      implanting cells. We report here that an additional limb can be formed from the
      flank when we implant fibroblast growth factor 4 (Fgf4)-expressing cells into the
      lateral plate mesoderm at the pre-limb bud stage. In a newly formed limb bud,
      expressions of both Sonic hedgehog and chick Fgf4, which are authentic
      morphogenetic signals from the zone of polarizing activity and the apical
      ectodermal ridge, respectively, are induced by the implanted cells. Thus, it is
      concluded that the competence for limb development is present along the flank of
      the chick embryo and that FGF4 applied ectopically at the pre-limb bud stage can
      alter the developmental fate of flank cells to become limb cells. The present
      experimental system will contribute to a further elucidation on how the limb is
      formed.

PMID- 7733974
TI  - The association and involvement of some members of the P1 protein family in a
      cell-free DNA replication of Xenopus eggs.
AB  - Two types of antibodies were prepared one directed against an oligopeptide
      specific to P1Cdc46, a mammalian homologue of yeast CDC46, and the other against
      an oligopeptide highly conserved in the P1 protein family. Immunoprecipitation
      with anti-P1Cdc46 antibody revealed that some members of the P1 protein family
      were coprecipitated with P1Cdc46 in the soluble fraction of Xenopus S phase
      extracts. Immunoblot analysis showed that all of the coprecipitated proteins
      reacted with the antibody against an oligopeptide, designated as a DEAD box
      motif, a highly conserved sequence in the P1 protein family. The immunodepleted
      extracts with anti-P1Cdc46 antibody-bound beads showed much lower activity of DNA
      replication than the mock-treated extracts. Recovery of replication was achieved
      by supplementing depleted extracts with the proteins eluted from anti-P1Cdc46
      antibody-bound beads. These findings suggest that the proteins contained in the
      P1 protein family were associated in the extracts and that the multiprotein
      complex of the family plays an essential role in a cell-free DNA replication of
      Xenopus eggs.

PMID- 7733975
TI  - Characterization of glucocorticoid response element of rat angiotensin II type 1A
      receptor gene.
AB  - The responsiveness of the rat angiotensin II type 1a and type 1b receptor (AT1a-R
      and AT1b-R) genes to glucocorticoid was examined in rat vascular smooth muscle
      cells (VSMCs) and the glucocorticoid response element (GRE) of the AT1a-R gene
      was characterized. Glucocorticoid induced an increase in AT1a-R mRNA levels,
      whereas AT1b-R mRNA levels were unaffected. The nuclear run-off assay indicated
      that the transcription of the AT1a-R gene, but not that of the AT1b-R gene, was
      increased by glucocorticoid. The mRNA stability of AT1a-R was unchanged by
      glucocorticoid. Promoter/chrolamphenicol acetyltransferase reporter analysis
      demonstrated that the 5'-flanking region of the AT1a-R gene was functional in rat
      VSMCs and established that the GRE motif between -770 to -756 could confer
      glucocorticoid responsiveness on the AT1a-R gene.

PMID- 7733976
TI  - Arachidonate metabolites affect the secretion of an N-terminal fragment of
      Alzheimer's disease amyloid precursor protein.
AB  - Amyloid precursor protein (APP) is degraded within the amyloid beta-protein (A
      beta) domain and its large soluble N-terminal fragment (secreted form of APP:
      APPs) is secreted into the culture media of many kinds of cells. We report here a
      quantitative increase in APPs secretion in the medium of human glioblastoma A172
      cells grown under serum-free conditions. When A172 cells were treated with
      inhibitors of the arachidonate cascade, a modulation of APPs secretion was
      observed; the addition of small amounts of indomethacin increased secretory
      cleavage, but higher doses suppressed it. Nordihydroguaiaretic acid (NDGA), an
      inhibitor of lipoxygenases, also inhibited APPs secretion. These results suggest
      that arachidonate metabolites of the leukotriene pathway may promote APPs release
      upon extracellular signaling via a signal transduction pathway, while metabolites
      of the prostaglandin pathway inhibit APPs secretion.

PMID- 7733977
TI  - Efficient expression of a heterodimer of bone morphogenetic protein subunits
      using a baculovirus expression system.
AB  - Recombinant baculoviruses as expression vectors for Xenopus bone morphogenetic
      protein (xBMP)-2, 4 and 7 were generated. The conditioned medium of insect cells
      infected with the virus for xBMP-2 or 4 showed strong alkaline phosphatase
      inducing activity in a mouse osteoblastic cell line, MC3T3-E1, although a large
      portion of the activity remained in the infected cells. In contrast, xBMP-7 was
      preferentially secreted into the medium, but had only weak activity. Conditioned
      media following simultaneous inoculation with the viruses for xBMP-7 and for xBMP
      2 or 4 showed a remarkably increased level of activity. The increased activity
      was clearly separated from other peaks derived from single infection on a cation
      exchange column and was found to arise from the disulfide-linked heterodimer
      consisting of xBMP-4 and 7 subunits by immunoblot analysis. The heterodimer also
      augmented osteocalcin production and parathyroid hormone-sensitivity more
      strongly than the homodimers. These results suggest that our expression system
      provides a convenient source of heterodimeric BMP with high osteogenic
      differentiation-inducing activity.

PMID- 7733978
TI  - Canthaxanthin biosynthesis by the conversion of methylene to keto groups in a
      hydrocarbon beta-carotene by a single gene.
AB  - Compounds that include (a) keto group(s) in a molecule are ubiquitous natural
      components. A novel gene involved in ketocompound biosynthesis, designated crtW,
      was isolated from the marine bacteria Agrobacterium aurantiacum and Alcaligenes
      PC-1 that produce ketocarotenoids such as astaxanthin. When this gene was
      introduced into Escherichia coli that accumulated beta-carotene due to the
      Erwinia carotenogenic genes, the E. coli transformants synthesized canthaxanthin,
      one of ketocarotenoids, which was identified after purification by its visible,
      FD-MS and 1H-NMR spectral analysis. It has been demonstrated for the first time
      that one gene encodes an enzyme "ketolase" that catalyzes the conversion of
      methylene groups of a hydrocarbon beta-carotene to keto groups for synthesizing
      canthaxanthin via echinenone.

PMID- 7733979
TI  - Neuromedin C binds Cu(II) and Ni(II) via the ATCUN motif: implications for the
      CNS and cancer growth.
AB  - Neuromedin C is a bombesin-like neuropeptide of the sequence Gly-Asn-His-Trp-Ala
      Val-Gly-His-Leu-Met-NH2. Characterization of the amino terminal Cu(II), Ni(II)
      binding motif in albumins led us to predict that any other peptides or proteins
      with the same motif would also bind Cu(II) and Ni(II) specifically (1). The
      primary sequence of neuromedin C contains the motif in the form Gly-Asn-His.
      Neuromedin C was therefore predicted to bind Cu(II) and Ni(II) specifically. The
      studies presented here confirm that prediction. These findings may have
      implications for the transport of Cu(II) within the central nervous system as
      well as both Menkes disease and Wilson disease. Both are genetic copper
      metabolism disorders which are characterized by severe neurological symptoms. In
      addition, Cu(II) may interfere with the neurotransmission or growth factor
      effects of neuromedin C.

PMID- 7733981
TI  - The isolation and characterization of the human cytochrome b5 gene.
AB  - From a series of lambda and cosmid libraries, we isolated DNA sequences
      corresponding to the complete coding region for the human cytochrome b5 (CYB5)
      gene. The overall gene organization was the same as the bovine and rabbit CYB5
      genes. One cosmid clone containing exon I plus the 5' flanking region was
      extensively characterized. From this clone we obtained 2000 bp of 5' flanking
      sequence, containing several distinctive GC rich regions, potential trans-acting
      factor binding sites and a 74 bp direct repeat. A series of deletion constructs
      were made in the pGL2 luciferase vector and then used to transfect HepG2 and K562
      cells. The data obtained suggest the presence of two promotors and one silencer
      region in the analyzed 5' sequence.

PMID- 7733980
TI  - Expression of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
      in Escherichia coli.
AB  - Chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was expressed
      in E. coli by using a pET3a T7 RNA polymerase-based expression system and was
      purified to homogeneity. The kinase and bisphosphatase of the expressed
      bifunctional enzyme had kinetic properties identical to those of the native
      chicken liver enzyme. However, the kinase activity of the chicken liver enzyme
      was 7-fold higher, while the bisphosphatase activity was 50 percent lower than
      those of the rat liver enzyme. Cys-256 of the rat liver bisphosphatase domain is
      not conserved in the chicken liver enzyme. A site-directed mutation was
      engineered at Cys-256 of the rat liver enzyme and the results indicate that the
      variation of this residue is not responsible for the difference in fructose-2,6
      bisphosphatase activity between the rat and chicken liver enzymes. It is
      postulated that the difference in the kinase/bisphosphatase activity ratios of
      these two enzymes results from differences in their NH2-terminal regions.

PMID- 7733982
TI  - Post-transcriptional regulation of thromboxane A2 synthase in U937 cells.
AB  - Translation of mRNAs is a process usually tightly coupled to transcription of
      genes. However, there are examples of mRNA species which accumulate without being
      translated. Some mRNAs present in oocytes and ferritin mRNA are the most studied
      models. Studying the biogenesis of thromboxane A2 (TXA2) in the promonocytic line
      U937, we have noted that in proliferating cells high levels of TXA2 synthase mRNA
      are detectable by Northern blot, whereas no TXA2 could be recovered in the
      medium. This has been explained on the basis of Western blot experiments: TXA2
      synthase was not detectable in proliferating cells, while a band of about 55 kd
      appears after treatment with the differentiating agent TPA. Immunofluorescence
      detection by confocal microscopy was in agreement with Immunoblot results. Thus,
      in U937 cells, TPA behaves as a regulator of translation of TXA2 synthase mRNA.
      We have further observed that the induced enzyme in U937 cells has many
      characteristics in common with the human monocytic enzyme: a long half life (> 24
      hrs), a marked stability during catalysis and similar Km and Vmax values. Thus,
      U937 cells are a good model to study the mechanism by which a mRNA is efficiently
      translated only after differentiation has been triggered.

PMID- 7733983
TI  - Aspartate-based inhibitor of interleukin-1 beta-converting enzyme prevents
      antitumor agent-induced apoptosis in human myeloid leukemia U937 cells.
AB  - We found that a novel protease inhibitor, benzyloxycarbonyl-Asp-CH2OC(O)-2,6
      dichlorobenzene (Z-Asp-CH2-DCB), which can preferentially inhibit interleukin-1
      beta-converting enzyme (ICE), completely blocked the apoptotic cell death of
      human myeloid leukemia U937 cells caused by etoposide, camptothecin, 1-beta-D
      arabinofuranosyl-cytosine and Adriamycin, as well as TNF-alpha, anti-Fas antibody
      and staurosporine. However, Z-Asp-CH2-DCB did not block non-apoptotic cell death
      of U937 cells caused by etoposide during prolonged incubation periods. These
      results indicate that ICE or ICE-like proteases inhibited by Z-Asp-CH2-DCB are
      involved in a common pathway of apoptotic cell death in U937 cells.

PMID- 7733984
TI  - Inhibition of angiotensin II- and potassium-mediated aldosterone secretion by KN
      62 suggests involvement of Ca(2+)-calmodulin dependent protein kinase II in
      aldosterone secretion.
AB  - Calcium is now acknowledged to play a major role as a cellular mediator of
      aldosterone secretion. However, the intricacies of the involvement of calcium in
      aldosterone secretion have not been clearly defined. We have shown here that
      calmodulin-dependent kinase II is involved in angiotensin II- and potassium
      evoked aldosterone secretion as judged by the marked inhibitory effect of KN-62,
      a specific inhibitor of such a kinase, on aldosterone secretion and this
      inhibition was similar to that produced by calmodulin inhibitor, W-7. These
      results further strengthen the case for the participatory role of calcium
      calmodulin system in aldosterone secretion.

PMID- 7733985
TI  - Maackia amurensis agglutinin discriminates between normal and chronic leukemic
      human lymphocytes.
AB  - Altered glycosylations of cell surface glycoproteins often accompany malignant
      transformation and lectins are useful for probing these alterations. Lymphocytes
      exhibit characteristic surface glycoproteins which serve as markers of cell
      status and development. The present work was undertaken to compare, on blots, the
      binding characteristics of membranes isolated from normal peripheral blood
      lymphocytes and chronic lymphatic leukemia cells to five different lectins, from
      Datura stramonium, Maackia amurensis, Sambucus nigra, Galanthus nivalis and
      Peanut. The Maackia amurensis lectin interacted with the normal lymphocytes but
      showed no binding to malignant cells. Hence, we suggest the Maackia lectin may be
      used to differentiate normal from leukemic cells.

PMID- 7733986
TI  - A novel guanylyl cyclase-A isoform: rat GC-A1 identification and mRNA
      localization to renal papilla and adrenal.
AB  - Natriuretic peptides modulate systemic blood pressure, diuresis and natriuresis
      through the stimulation of cGMP production by guanylyl cyclase-coupled
      natriuretic peptide receptor-A and -B (GC-A and GC-B). A novel isoform of GC-A,
      GC-A1, has been identified which is the result of differential splicing of a new
      exon, 5a. This 9 bp sequence is predicted to add proline-cysteine-glutamine to
      the extracellular juxtamembrane region of the receptor protein. Transcripts for
      GC-A1 are expressed primarily in the renal papilla and adrenal. In these tissues,
      its abundance relative to GC-A was 1-2.5% as assessed by quantitative PCR.

PMID- 7733987
TI  - The local dynamics of the active site region of glycogen phosphorylase B.
AB  - The parameters characterizing the quenching of fluorescence emitted by the
      coenzyme (pyridoxal-5-phosphate) of phosphorylase b (EC 2.4.1.1) by anions are
      good indicators of conformational/dynamic changes at the active center.
      Reinvestigation of this quenching process resulted in a non-linear Stern-Volmer
      plot. This non-linearity is described by a simple kinetic model which assumes two
      parallel processes, one represented by bound and the second by free quencher
      molecules. Analysis of separate parts of the non-linear Stern-Volmer plot results
      in the values of rate constants for the bound and free quencher molecules as well
      as the value of dissociation constant of the anions.

PMID- 7733988
TI  - Cloning of rat obese cDNA and its expression in obese rats.
AB  - The mouse obese gene product, expressed specifically in adipose tissue, regulates
      energy balance in mice. Mutation of the obese gene results in marked obesity and
      type II diabetes as part of a syndrome that resembles morbid obesity in humans.
      Here we report the cloning and sequencing of rat obese cDNA. Neither alterations
      of nucleotide sequence in the coding region nor changes of the gene structure
      were found in two rat strains with obesity, Zucker (fa/fa) and Otsuka Long Evans
      Tokushima Fatty. The expression level of obese mRNA in adipose tissue of Zucker
      (fa/fa) rat was found to be about 4 times that in lean littermates, suggesting
      some mutation or abnormal expression of the receptor for the obese product in
      obese rats of this strain.

PMID- 7733989
TI  - Antioxidant, probucol, can inhibit the generation of hydrogen peroxide in islet
      cells induced by macrophages and prevent islet cell destruction in NOD mice.
AB  - The preventive effect of antioxidant on the islet cell destruction in NOD mice
      was studied. Oral administration of probucol prevented the development of
      cyclophosphamide induced diabetes in NOD mice (incidence of diabetes; probucol:
      0/10 vs. control: 9/15) As in vitro studies, the effects of probucol on the
      generation of H2O2 in the content of H2O2 in islet cells co-cultured with M phi
      were measured. Intracellular oxidation of 2'7'-dichlorofluorescin by H2O2 was
      analyzed by flow cytometry. The probucol-treated M phi induced less marked
      increase of H2O2 in islet cells in comparison with control M phi. The generation
      of H2O2 by M phi in islet cells from treated mice was less marked than that in
      controls. These results suggest that the preventive effect of probucol may be
      mediated by protection of islet cells from oxidative stress induced by M phi.

PMID- 7733990
TI  - Pez: a novel human cDNA encoding protein tyrosine phosphatase- and ezrin-like
      domains.
AB  - We have isolated cDNAs from normal human breast tissue and breast tumour cells
      that encode a protein (pez) with features of a novel non-receptor tyrosine
      phosphatase possessing N-terminal sequence homology to the ezrin-band 4.1-merlin
      radixin protein family. Northern blot analysis indicates that pez is expressed in
      a variety of human tissues including kidney, skeletal muscle, lung and placenta.
      Fluorescence in situ hybridization has mapped pez to chromosome 1 region q32.2
      41. Sequence identity to a characterized polymorphic marker confirms this
      localization.

PMID- 7733991
TI  - Site-directed mutagenesis of herpes simplex virus type 1 thymidine kinase opposes
      the importance of amino acid positions 251, 321 and 348 for selective recognition
      of substrate analogs.
AB  - Seven site-directed mutants representing step-by-step transitions from the
      thymidine kinase (TK) of Herpes Simplex Virus type 1 (HSV 1) strain F to that one
      of strain SC16 were constructed, recombinantly produced and kinetically
      characterized in order to identify which of three differences in the amino acid
      sequence of these two TKs is/are responsible for their difference in substrate
      specificity. The preference of these two TKs for the substrate analogs aciclovir
      and ganciclovir was reported to be in reverse order (4.5), suggesting one of the
      amino acids in position 251 (cys or gly), 321 (ser or pro) and 348 (val or ile)
      of the HSV 1 wildtype TKs to be important for selective substrate recognition.
      However, the results of our study do not support this hypothesis.

PMID- 7733992
TI  - Islet phosphoinositide hydrolysis and insulin secretory responses from
      prediabetic fa/fa ZDF rats.
AB  - The sequence of events that culminate in the development of diabetes in the fa/fa
      Zucker diabetic fatty (ZDF) rat is unclear. In the present series of experiments
      islets from 5 week old prediabetic fa/fa male rats were isolated and their
      phosphoinositide (PI) hydrolysis and insulin secretory responses compared to
      those obtained from lean nondiabetic age- and weight-matched control rats. Peak
      first and second phase insulin secretory responses to 20mM glucose averaged 77 +/
      10 (mean +/- SE, n = 7) and 491 +/- 47 pg/islet/min from lean, nondiabetic
      control islets. The comparable responses from fa/fa prediabetic rat islets were
      significantly greater, 264 +/- 51 and 810 +/- 78 pg/islet/min. In a parallel
      fashion 3H-inositol efflux and inositol phosphate responses from prediabetic rat
      islets were also greater than comparable control responses. These findings
      demonstrate that significant increases in the phospholipase C-mediated hydrolysis
      of islet PI pools and insulin release in response to hyperglycemic stimulation
      can be detected prior to the emergence of diabetes in the fa/fa ZDF rat. These
      early changes in beta cell responsiveness to glucose may contribute to the
      hyperinsulinemia and subsequent insulin resistance characteristic of this animal
      model of non-insulin dependent diabetes mellitus.

PMID- 7733993
TI  - Identification of a new bovine MHC class II DRB allele by nucleotide sequencing
      and an analysis of phylogenetic relationships.
AB  - Three overlapping cDNA clones coding for the bovine major histocompatibility
      complex (MHC) class II DR beta chain were isolated. A clone NR1 encoded a primary
      translated product of 266 amino acids, 29 of which were deduced to form a signal
      peptide and 237 to form the mature polypeptide. The protein predicted from this
      cDNA appeared to have all the features expected of an expressed MHC class II
      molecule. Comparison of the sequences and construction of a phylogenetic tree
      revealed that NR1 represents a BoLA-DRB3 gene and not a BoLA-DRB1 or BoLA-DRB2
      pseudogene. NR1 and ovine sequences exhibited the greatest overall similarity
      among sequences from various mammalian species, followed by the equivalent human
      sequences. Indeed, the bovine allele was more closely related to certain ovine
      alleles than to other bovine alleles. A large number of replacement substitutions
      were identified when beta 1 domains encoded by NR1 and each of the 36 distinct
      BoLA-DRB3 alleles were compared, and most of the allelic variations were found in
      regions that are commonly polymorphic in DRB sequences from different species and
      correspond to the predicted antigen-recognition site. Thus, the predicted
      structure of the unique NR1 allele for BoLA-DRB3 further confirms the overall
      conservation of the product of this locus, as previously established from studies
      in rodent and man.

PMID- 7733995
TI  - 1995 reference guide.

PMID- 7733994
TI  - Bioactivation of 5-hydroxymethyl-2-furaldehyde to an electrophilic and mutagenic
      allylic sulfuric acid ester.
AB  - 5-Hydroxymethyl-2-furaldehyde (HMF), a ubiquitous food contaminant, has been
      proposed to be metabolically activated through sulfonation of its allylic
      hydroxyl functional group. In support of this idea, we have found the strong
      direct mutagenicity of chemically synthesized sulfuric acid ester, 5
      sulfooxymethylfurfural (SMF), in Salmonella typhimurium TA104. The intrinsic
      mutagenicity of this reactive ester was significantly inhibited by glutathione
      and glutathione S-transferase activity in dialyzed rat liver cytosol. The
      metabolic formation of SMF was elucidated by enhanced mutagenicity of HMF in the
      presence of rat hepatic cytosol enriched with the sulfo-group donor, 3'
      phosphoadenosine-5'-phosphosulfate (PAPS). The PAPS- and cytosol-dependent
      mutagenicity of HMF was markedly lessened by sulfotransferase inhibitors such as
      2,6-dichloro-4-nitrophenol and dehydroepiandrosterone. These results suggest that
      HMF can be metabolically activated to an allylic sulfuric acid ester which may
      play a role as an ultimate electrophilic metabolite in toxification of the parent
      compound in vivo.

PMID- 7733996
TI  - Ideas into print. ASHA's scholarly journals.

PMID- 7733997
TI  - The FACS of life ASHA facs--a functional outcome measure for adults.

PMID- 7733998
TI  - Career selection and satisfaction in the professions.

PMID- 7733999
TI  - Sister Marie de Montfort.

PMID- 7734000
TI  - Let's talk ... for people with special communication needs.

PMID- 7734001
TI  - Efficacy of antibiotic-coated catheters in preventing subcutaneous Staphylococcus
      aureus infection in rabbits.
AB  - Vascular catheters coated with antiinfective compounds were evaluated as to their
      ability to prevent Staphylococcus aureus catheter infection in a rabbit model.
      Zones of inhibition of agar surface-plated S. aureus demonstrated the following
      hierarchy: dicloxacillin and clindamycin were each better than fusidic acid or
      chlorhexidine, which were better than ciprofloxacin, cefotaxime, or cefuroxime.
      In vivo half-lives of inhibitory activity for clindamycin and dicloxacillin were
      5.6 and 17.7 h, respectively, with apparent first-order kinetics. Chlorhexidine
      disappeared in vivo with apparent two-compartment kinetics: first-compartment
      t1/2, 16.8 h; second-compartment t1/2, 115.6 h. In a rabbit model, dicloxacillin,
      clindamycin, fusidic acid, and chlorhexidine decreased the risk of infection
      compared with uncoated control catheters (P < .05). For dicloxacillin,
      clindamycin, and chlorhexidine, this was true even if the S. aureus inoculation
      was delayed 48 or 96 h after catheter implantation. These data suggest that
      vascular catheters with antiinfective coatings should be investigated further in
      hospitalized patients.

PMID- 7734002
TI  - [Favorable in vitro effect of pentoxifylline on damaged lymphocyte migration in
      arteriosclerosis obliterans and systemic lupus erythematosus].
AB  - Decreased blood cell--e.g. lymphocyte--motility is seen in a number of vascular
      and autoimmune diseases. Pentoxifylline (Pf) shows a well-known therapeutic
      effect in several vascular alterations by causing the redistribution of blood
      cell cytoskeleton and increased microcirculation. As most literary data on Pf
      concern red blood cells and granulocytes authors here investigated the effect of
      Pf on previously decreased lymphocyte migration and chemotaxis. Results of in
      vitro studies suggest that Pf enhances impaired lymphocyte motility in
      obliterative arteriosclerosis and systemic lupus erythematosus and thus may also
      be introduced in the treatment of polysystemic autoimmune diseases.

PMID- 7734003
TI  - [Studying the course of HIV-1 infection in cell culture].
AB  - The hallmark of AIDS is the gradual loss of CD4+ T-lymphocytes, in spite of their
      infection in low ratio. The pathomechanism is hardly known, therefore, the
      production of HIV-1 and certain aspects of cell death were studied. Infectivity
      was decreased by the acidification of culture media. C8166 cells transformed by
      HTLV-I and exhibiting features of both immature T lymphocytes and myeloid cells,
      produced transient protoplasmic surface extrusions, similar to the hairy cell
      leukemia. These can have a role in the direct cell-to-cell spread of HIV-1.
      Polarization of nuclei and cell organelles as well as sites of virus budding
      during syncytium formation resembled the directed lymphokine secretion. Both cell
      membrane and intravacuolar buddings were characteristic. Abnormal virus particles
      also were seen. Certain morphological signs resembled apoptosis. Fibroblast
      cultures in the presence of HIV-1 infected lymphoid cells were arrested in growth
      and underwent cell death without syncytium formation. The results draw attention
      to the faster development of AIDS in the case of HIV-1 infection of precursor
      immune cells. Double infection by HTLV and HIV-1 can result in atypical
      leukemias.

PMID- 7734004
TI  - [Burns with lighter gas].
AB  - Attention is drawn to a particularly dangerous party activity. Balloons filled
      with lighter gas so as to float are used for party decorations. A case of hand
      burn caused by accidentally lighting such a balloon with a cigarette is reported.
      The method is strongly advised against, it is a much better idea to use helium
      for such purposes.

PMID- 7734005
TI  - [Ethical aspects of dismissing the help of an interpreter].

PMID- 7734006
TI  - [Korsakoff syndrome].

PMID- 7734007
TI  - [Post-laryngitis sepsis caused by Fusobacterium necrophorum: Lemierre syndrome].

PMID- 7734008
TI  - [Avoid unnecessary psychiatrization].

PMID- 7734009
TI  - Comparison of sedative recovery time after midazolam versus diazepam
      administration.
AB  - OBJECTIVE: To compare the sedative recovery rate pharmacology of intravenous
      midazolam vs. diazepam when used for short-term sedation. DATA SOURCES: English
      language articles were identified through a search of the MEDLINE and InPharma
      databases. Bibliographies of retrieved articles were examined for relevant
      articles. STUDY SELECTION: Twenty-eight studies were identified based on a priori
      inclusion criteria. Eight trials had enough information to combine results for
      sedative recovery rate. DATA EXTRACTION: The difference in mean time to sedative
      recovery, weighted by sample size, was determined. DATA SYNTHESIS: Of the 28
      trials, eight reported a significantly faster sedation recovery rate from
      diazepam vs. midazolam, whereas 19 trials reported no difference in sedative
      recovery time, and a single trial reported that midazolam offered significantly
      faster recovery from sedation than diazepam. A commonly defined time to sedative
      recovery event was available for only eight trials. The median dosing ratio for
      these eight trials was 2.1:1 for diazepam over midazolam. The weighted mean time
      difference was 4 mins 16 secs in favor of diazepam as the agent from which
      patients recover more quickly. CONCLUSIONS: These results firmly underscore the
      understanding that elimination half-lives of benzodiazepines do not necessarily
      correspond with their sedative pharmacodynamic effects, and we conclude that
      there are no clinically important sedative recovery rate differences between
      midazolam and diazepam, while midazolam is a more expensive agent.

PMID- 7734010
TI  - Effect of lovastatin on early carotid atherosclerosis and cardiovascular events.
      Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group.
AB  - BACKGROUND: HMG CoA reductase inhibitors (or statins), a new class of lipid
      lowering compounds, have raised expectations for more widespread use than that of
      the older lipid-lowering drugs. Not only are they more effective in lowering LDL
      cholesterol, but they are better tolerated as well. No data exist concerning the
      effect of statins on early carotid atherosclerosis and clinical events in men and
      women who have moderately elevated LDL cholesterol levels but are free of
      symptomatic cardiovascular disease. METHODS AND RESULTS: Lovastatin (20 to 40
      mg/d) or its placebo was evaluated in a double-blind, randomized clinical trial
      with factorial design along with warfarin (1 mg/d) or its placebo. This report is
      limited to the lovastatin component of the trial. Daily aspirin (81 mg/d) was
      recommended for everyone. Enrollment included 919 asymptomatic men and women, 40
      to 79 years old, with early carotid atherosclerosis as defined by B-mode
      ultrasonography and LDL cholesterol between the 60th and 90th percentiles. The 3
      year change in mean maximum intimal-medial thickness (IMT) in 12 walls of the
      carotid arteries was the primary outcome; change in single maximum IMT and
      incidence of major cardiovascular events were secondary outcomes. LDL cholesterol
      fell 28%, from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months (P < .0001), in
      the lovastatin groups and was largely unchanged in the lovastatin-placebo groups.
      Among participants not on warfarin, regression of the mean maximum IMT was seen
      after 12 months in the lovastatin group compared with the placebo group; the 3
      year difference was statistically significant (P = .001). A larger favorable
      effect of lovastatin was observed for the change in single maximum IMT but was
      not statistically significant (P = .12). Five lovastatin-treated participants
      suffered major cardiovascular events--coronary heart disease mortality, nonfatal
      myocardial infarction, or stroke--versus 14 in the lovastatin-placebo groups (P =
      .04). One lovastatin-treated participant died, compared with eight on lovastatin
      placebo (P = .02). CONCLUSIONS: In men and women with moderately elevated LDL
      cholesterol, lovastatin reverses progression of IMT in the carotid arteries and
      appears to reduce the risk of major cardiovascular events and mortality. Results
      from ongoing large-scale clinical trials may further establish the clinical
      benefit of statins.

PMID- 7734011
TI  - Tracheal tube placement during percutaneous dilational tracheostomy.

PMID- 7734012
TI  - Tissue distribution of the human MDR3 P-glycoprotein.
AB  - BACKGROUND: P-glycoproteins (Pgps) belong to a family of well conserved plasma
      membrane proteins with two members in humans: MDR1 and MDR3. The MDR1 Pgp can
      transport drugs; the murine homologue of MDR3, mdr2, was recently shown by us to
      be involved in transport of the phospholipid phosphatidylcholine (lecithin) into
      bile. EXPERIMENTAL DESIGN: We have determined the MDR3 mRNA levels in a panel of
      human tissues by RNase protection. We have also generated polyclonal antibodies
      specific for the MDR3 Pgp. Detection of the MDR3 Pgp in human tissues with these
      antibodies was by a streptavidin-ABC procedure. RESULTS: The RNase protection
      results show that expression of the MDR3 gene has a more restricted distribution
      than that of MDR1. A high level of MDR3 mRNA was detected in the liver and in low
      levels in the adrenal gland, heart, striated muscle, spleen, and tonsil. In all
      of these tissues, some of the previously described splice variants of MDR3 were
      abundantly expressed. No indications were found for a tissue-specific regulation
      of alternative splicing of the MDR3 pre-mRNA. Two MDR3 Pgp-specific antibodies
      stained the bile canalicular membrane of hepatocytes across the entire liver
      lobule. No staining was found in the epithelial cells of the bile ductules and
      gall bladder, indicating that the staining at these sites with C219, a monoclonal
      antibody that recognizes both MDR1 and MDR3 Pgp, (mainly) represents the MDR1
      Pgp. No MDR3 was detected by specific antibodies in the adrenal gland, spleen,
      and muscle. Since no staining was reported with MDR1-specific antibodies in
      muscle either, our results indicate that the C219 staining in some fibers of
      striated muscle represents a cross-reaction with another protein. One of the
      human MDR3-specific antibodies cross-reacted with the highly homologous mouse
      mdr2 Pgp. Staining with this antibody showed that the distribution of this
      protein in mouse liver and striated muscle is very similar to that of MDR3 Pgp in
      human tissues. CONCLUSIONS: The highest expression of the MDR3 Pgp was found in
      liver in the canalicular membranes of hepatocytes. This is in agreement with a
      role for MDR3 in the transport of phospholipid into bile.

PMID- 7734013
TI  - Severe acute hepatitis B infection after vaccination.

PMID- 7734014
TI  - Lack of rifabutin resistance with prophylaxis for disseminated Mycobacterium
      avium complex.

PMID- 7734015
TI  - The efficacy of acarbose in the treatment of patients with non-insulin-dependent
      diabetes mellitus. A multicenter controlled clinical trial.
AB  - OBJECTIVE: To evaluate the long-term efficacy of acarbose, an alpha-glucosidase
      inhibitor, in improving glycemic control in patients with non-insulin-dependent
      diabetes mellitus. DESIGN: A 1-year, multicenter, randomized, double-blind,
      placebo-controlled study. SETTING: Seven university-affiliated, community-based,
      tertiary care diabetes clinics. PATIENTS: 354 patients with non-insulin-dependent
      diabetes mellitus were recruited; 77 were being treated with diet alone, 83 with
      diet and metformin, 103 with diet and sulfonylurea, and 91 with diet and insulin.
      Patients in each treatment group were randomly assigned to either acarbose or
      placebo for 1 year. Eighty-seven percent of patients receiving acarbose and 92%
      of those receiving placebo were included in the efficacy analysis (n = 316).
      MEASUREMENTS: At baseline and at 3-month intervals, levels of hemoglobin A1c
      (HbA1c), fasting and postprandial plasma glucose, fasting and postprandial serum
      C-peptide, and fasting serum lipids were measured. RESULTS: Compared with
      placebo, acarbose treatment caused a significant decrease in the mean
      postprandial plasma glucose peak (90 minutes) in all four groups (19.0 +/- 0.4
      mmol/L to 15.5 +/- 0.4 mmol/L; P < 0.001). Analysis of the postprandial plasma
      glucose incremental area under the curve showed that the change from baseline to
      the end of the treatment period differed for placebo and acarbose recipients by
      4.73 mmol.h/L in the diet alone group (P < 0.001), 2.06 mmol.h/L in the metformin
      group (P = 0.01), 2.65 mmol.h/L in the sulfonylurea group (P < 0.001), and 3.13
      mmol.h/L in the insulin group (P = 0.001). Corresponding decreases in HbA1c
      levels occurred; these were 0.9% in the diet alone group (P = 0.005), 0.8% in the
      metformin group (P = 0.011), 0.9% in the sulfonylurea group (P = 0.002), and 0.4%
      in the insulin group (P = 0.077). Acarbose did not significantly affect mean
      serum C-peptide or mean serum lipid levels. CONCLUSIONS: Acarbose improved long
      term glycemic control in patients with non-insulin-dependent diabetes mellitus
      regardless of concomitant antidiabetic medication.

PMID- 7734016
TI  - Clinical significance of heparin in the residual pump oxygenator blood, reinfused
      postoperatively after cardiopulmonary bypass.
AB  - Postcardiopulmonary bypass (CPB) heparin levels and thrombin time were measured
      in 20 patients following routine open cardiac operations. There was a
      statistically significant increase in heparin concentration and thrombin time
      ratio on completion of transfusion of the residual pump oxygenator blood. An hour
      after the end of the transfusion there was no statistically significant
      difference in the heparin concentration and thrombin time ratio compared to
      values before and immediately after transfusion. We also observed a significant
      decrease in the chest drainage over a period of four hours which was unrelated to
      plasma heparin level. Measurements of thrombin time in the post bypass period
      closely follow plasma heparin levels. If postoperative bleeding arose it was due
      to inadequate surgical haemostasis or coagulation defect other than residual
      heparinization. Thus this confirms further that heparin is not the sole
      aetiological factor in postoperative bleeding post-CPB.

PMID- 7734017
TI  - Is the evidence for homoeopathy reproducible?

PMID- 7734018
TI  - Gynaecological monitoring during tamoxifen therapy.

PMID- 7734019
TI  - Plague in India.

PMID- 7734020
TI  - Acute hepatitis B infection after vaccination.

PMID- 7734021
TI  - Old wine in a new bottle: evolution by another name.

PMID- 7734022
TI  - Confusion over OTC product lines.

PMID- 7734023
TI  - Manpower and education.

PMID- 7734024
TI  - Inflation of the cuff of the laryngeal mask.

PMID- 7734025
TI  - Preventing STDs.

PMID- 7734026
TI  - Effects of disopyramide on diastolic function in hypertrophic cardiomyopathy.

PMID- 7734027
TI  - 'Cytokines' in sera of lower vertebrates.

PMID- 7734028
TI  - The effects of levosulpiride on gastric and gall-bladder emptying in functional
      dyspepsia.
AB  - BACKGROUND: 50% of patients with functional dyspepsia have delayed gastric
      emptying. Levosulpiride is an orthopramide drug that stimulates gastrointestinal
      motility. Aim of our study was to evaluate the effect of levosulpiride on
      symptoms and gastric and gall-bladder emptying, in dyspeptic patients. METHODS:
      Thirty adult patients, treated for 20 days with levosulpiride (75 mg/day) or
      placebo, were evaluated in a randomized double-blind study. Symptoms were
      assessed by a cumulative index and overall intensity (visual analogue line).
      Gastric and gall-bladder emptying were evaluated by epigastric impedance (liquid
      meal) and real-time ultrasonography (mixed meal). RESULTS: Levosulpiride, with
      respect to placebo, accelerated the mean gastric half-emptying time of liquids (P
      < 0.05), gastric emptying (P < 0.001 at 180 min; P < 0.05 at 240 min), and gall
      bladder emptying (P < 0.05 at 60 and 120 min) emptying after a solid-liquid mixed
      meal. Both the mean cumulative index (P < 0.05) and the overall intensity (P <
      0.025) of dyspeptic symptoms were reduced significantly by levosulpiride.
      CONCLUSIONS: Our results showed that levosulpiride can be usefully employed in
      patients affected by functional dyspepsia.

PMID- 7734029
TI  - Growth hormone secretion after the administration of GHRP-6 or GHRH combined with
      GHRP-6 does not decline in late adulthood.
AB  - OBJECTIVE: Growth hormone (GH) secretion in middle and late adulthood declines
      with age. However, the precise mechanisms causing this impairment in GH release
      are unknown. His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) is a synthetic compound
      that releases GH in a dose related and specific manner in several species,
      including man. In order to gain a further insight into disrupted GH secretion in
      late adulthood, we evaluated GH responses to GHRP-6 or GHRH, administered either
      alone or in combination, in healthy young and late adulthood groups of subjects.
      DESIGN: All subjects underwent three different tests carried out in random order
      and separated by at least one week. Tests were performed at 0900 h after an
      overnight fast. GHRH (100 micrograms), GHRP-6 (90 micrograms) either alone or in
      combination were administered as an i.v. bolus. SUBJECTS: Groups of healthy young
      (mean +/- SEM 22 +/- 1.1 years, n = 9) and older adult subjects (59.5 +/- 1.7
      years, n = 9) were studied. MEASUREMENTS: Serum GH levels were measured by
      radioimmunoassay. RESULTS: In the group of young adult subjects the combined
      administration of GHRH and GHRP-6 elicited a greater GH increase than GHRH alone
      (F = 21.9, P < 0.001) or GHRP-6 alone (F = 6.2, P = 0.01). Similarly, the
      response to the combined stimuli was also greater than with GHRH alone (F = 21.8,
      P < 0.001) or GHRP-6 alone (F = 23.9, P < 0.001) in the late adulthood group of
      subjects. GH responses to GHRH were greater in younger than in older subjects (F
      = 3.45, P = 0.03). In contrast, GH responses to either GHRP-6 (F = 0.71, P = NS)
      or combined GHRH plus GHRP-6 administration (F = 0.68, P = NS) were not
      significantly different between the two groups. CONCLUSIONS: These data show that
      GH responses to GHRP-6 are much greater than to GHRH in late adulthood. The
      marked increase of plasma GH levels observed after administration of GHRP-6 alone
      or in combination with GHRH indicates that impaired GH secretion in late
      adulthood is a functional and potentially reversible state.

PMID- 7734030
TI  - Coronary artery bypass surgery and minor aortic stenosis--to replace or not to
      replace?
AB  - Seven patients with a mean age of 65 years (range 50-76 years) who had minor
      aortic valve gradients (less than 25 mmHg) at preoperative cardiac
      catheterization underwent coronary artery bypass surgery without aortic valve
      surgery, but required a second operation for aortic valve replacement between
      five and nine years later because of symptomatic aortic valve stenosis with a
      valve gradient which had increased to between 60 and 100 mmHg. Serial hemodynamic
      observations in patients with aortic stenosis have demonstrated that the rate at
      which stenosis progresses is widely variable. However, replacement of aortic
      valves at the time of initial coronary artery surgery may subject the patients to
      an increased risk of operative mortality and prosthetic valve-related
      complications. On the other hand, the patient may miss the opportunity to obtain
      maximum benefit from valve replacement before deterioration of left ventricular
      function, particularly in the presence of coronary artery disease, and there are
      also the risks of resternotomy. We are currently inclined to replace the aortic
      valve in coronary patients with asymptomatic aortic stenosis, but our experience
      is not sufficient to draw final conclusions and the relevant literature does not
      provide a clear guidance. The aim of this publication is to expose this dilemma.

PMID- 7734031
TI  - Apoptosis and autoimmunity.

PMID- 7734032
TI  - Associated autoimmunity in Addison's disease.
AB  - As the last extensive series of patients with Addison's disease and coincident
      autoimmune phenomena were published approximately two decades ago, we studied the
      cause of the disease, the prevalence of autoimmune disorders and the frequency of
      occurrence of autoantibodies in 91 patients (31 men and 60 women, mean age 45.3
      years-old, range 12-77) with Addison's disease. The cause of Addison's disease in
      six patients was tuberculosis (6.6%), and autoimmune adrenalitis was considered
      to be the cause in 83 patients (91.2%). In two patients (2.2%) other causes were
      responsible for Addison's disease. In 47% of the patients with autoimmune
      Addison's disease at least one other autoimmune disorder was present. Primary
      hypothyroidism had the highest prevalence (20.5%), followed by vitiligo (9.6%),
      non-toxic goiter (8.4%), premature menopause (7.3% of the women), Graves' disease
      (6%), pernicious anaemia (4.8%), Sjogren's disease (2.4%), hypoparathyroidism
      (1.2%), type 1 diabetes mellitus (1.2%) and coeliac disease (1.2%). The frequency
      of autoantibodies in the patients with autoimmune Addison's disease was: adrenal
      antibodies (82.7%), antibodies against microsomal antigens (58%), thyroglobulin
      antibodies (23.4%), parietal cell antibodies (19.8%), pancreatic islet cell
      antibodies (6.2%) and ovary antibodies (3.7% of the women). In comparison with
      other extensive series of patients with Addison's disease, we found the highest
      prevalence of autoimmune adrenalitis as the cause of Addison's disease, the
      highest prevalence of hypothyroidism and vitiligo as concomitant autoimmune
      disorders and the lowest prevalence of type 1 diabetes mellitus.

PMID- 7734033
TI  - Non-linkage of a T-cell receptor gamma chain microsatellite (D7S485) to
      rheumatoid arthritis in multiplex families.
AB  - A highly informative microsatellite marker, D7S485, from the T-cell receptor
      gamma (TCRG) locus, has been used to study segregation of TCRG genes in 26
      multiplex rheumatoid arthritis (RA) families. We used the sib-pair method to
      assess excess identity-by-descent sharing among affected members in these
      families and the LINKAGE package of programs was used to calculate two-point lod
      scores for the D7S485 marker. There was no evidence for segregation of TCRG genes
      with RA in affected siblings and significantly negative lod scores were obtained
      from linkage analyses using both autosomal dominant and recessive models of
      inheritance.

PMID- 7734034
TI  - The murine autologous mixed lymphocyte response: distribution of stimulator
      cells.
AB  - Previous studies have shown that neonatal, but not adult, murine thymic T cells
      proliferate when co-cultured with syngeneic, adult splenic B cells. Evidence
      suggests that expansion of such self-reactive T cells precedes their clonal
      deletion or functional inactivation (anergy). This mechanism may be of particular
      significance for establishing peripheral (extrathymic) tolerance. In order to
      assess the autostimulatory capacity of B cells present in a variety of lymphoid
      tissues, neonatal T cells were cultured with Peyer's patch and peritoneal cavity
      cells. The results indicate that B cells in these tissues readily induce T cell
      proliferation. Evidence suggests that the B-1 B cell subpopulation is not
      obligatory for this process. Self-reactive T cells were evident in the spleen of
      young mice, substantiating a role for B cells in maintaining peripheral
      tolerance. The results suggest that B cells involved in this process are
      distributed in a variety of lymphoid organs.

PMID- 7734035
TI  - Effect of long-term anti-CD4 or anti-CD8 treatment on the development of lpr CD4-
      CD8- double negative T cells and of the autoimmune syndrome in MRL-lpr/lpr mice.
AB  - We have determined the effect of anti-CD4 or anti-CD8 monoclonal antibody (mAb)
      treatment from birth on the generation of the lpr CD4- CD8- double-negative (DN)
      T cell subset and on the development of lupus-like autoimmune syndrome in MRL
      lpr/lpr mice. Both anti-CD4 and anti-CD8 mAb treatments resulted in a marked
      inhibition of lymph-adenopathy, whereas the development of the lpr DN T cells and
      of the lupus-like autoimmune syndrome strikingly differed in these two groups of
      mice. The treatment with anti-CD8 mAb almost completely blocked the appearance of
      the lpr DN T cells without any significant effect on the development of lupus
      like autoimmune syndrome in MRL-lpr/lpr mice. In contrast, mice treated with anti
      CD4 mAb failed to develop a lupus-like syndrome, while they still developed the
      lpr DN T cell subset, the predominant population in their lymph nodes, although
      absolute numbers were markedly diminished. Our results support the idea that CD8+
      T cells are a major source of the lpr DN T cells, and that the lpr DN T cells
      play a minor, if any, role in the pathogenesis of lupus-like autoimmune syndrome
      in MRL-lpr/lpr mice.

PMID- 7734036
TI  - Characterization of the procoagulant-inducing factor derived from the plasma of
      BXSB mice.
AB  - Plasma procoagulant activity inducing factor (PIF) is a spontaneously occurring,
      potent inducer of macrophage procoagulant activity (PCA) in the male BXSB murine
      model of systemic lupus erythematosus. The physical characteristics of PCA
      induction by PIF, aggregated mouse IgG, and lipopolysaccharide (LPS) were
      compared. Both aggregated IgG and PIF-induced PCA were heat, acid and alkali
      sensitive. In contrast, LPS-induced PCA was heat resistant and only partially
      acid and alkali sensitive. Plasma containing PIF was fractionated on Sephacryl S
      300. The PIF activity localized to the first protein peak, molecular weight
      400,000 to 900,000 daltons. Analysis of peak 1 by an enzyme-linked immunosorbent
      assay showed the presence of IgM, IgA and IgG. This was confirmed by Western blot
      analysis using 125I-labelled goat anti-mouse IgM, IgA and IgG probes. The
      concentration of PIF increased with Sephacryl S-300 chromatography and was
      reduced by removal of IgG, but not IgA or IgM by affinity chromatography. Peak 1
      did not contain DNA as revealed by ethidium bromide staining. Thus, IgG from the
      plasma of BXSB mice, a strain which develops lupus nephritis, stimulates
      macrophages to express PCA, accounting for PCA induction in the BXSB model of
      murine lupus.

PMID- 7734037
TI  - Induction of flare-up reactions in rat antigen-induced arthritis.
AB  - Flare-up reactions were induced in the rat chronic antigen-induced arthritis
      model (AIA), similar to those in mice and rabbits. After two consecutive
      immunizations (500 micrograms each, Day -21 and -14) with methylated bovine serum
      albumin (mBSA) in complete Freund's adjuvant (CFA), a biphasic primary arthritis
      was induced on Day 0 by intra-articular (i.a.) injection of 100 micrograms mBSA.
      The acute arthritic phase lasted 1 week, followed by chronic, mild joint
      swelling. Flare-up could then be induced on Day 40 by a second i.a. injection of
      10-100 micrograms mBSA into the knee, with maximal flare-up reaction 2 days
      following the i.a. injection, and a return to chronic levels within 2 weeks. On
      Day 6 after induction of the flare-up, the inflamed joint showed massive
      cartilage and bone destruction; high numbers of alpha beta-T-cell-receptor
      positive cells and macrophages, but only a few IL-2-receptor-carrying cells were
      detected in the inflamed synovial membrane. Induction of a second flare-up, 40
      days after the first one, was possible by i.a. injection of 100 micrograms mBSA.
      Unlike in the mouse model, intravenous injection of up to 10 mg mBSA failed to
      induce flare-ups in the chronically inflamed joint.

PMID- 7734038
TI  - Absence of gluten-specific T lymphocytes in the skin of patients with dermatitis
      herpetiformis.
AB  - Dermatitis Herpetiformis (DH) is an immunobullous skin disease with an associated
      gluten-sensitive enteropathy. Withdrawal of gluten from the diet leads to the
      resolution of both the skin lesions and the enteropathy. A T cell-mediated immune
      response to gluten has been implicated in the damage to the gut; the possible
      gluten specificity of the T cell infiltrate in DH skin lesions has not, however,
      been investigated. T cell lines (TCL) were therefore established from the skin
      lesions of eight patients with DH by culturing skin fragments for 11-17 days with
      a medium supplemented with 20 U/ml of IL-2. In three cases, gliadin (fraction of
      gluten toxic to the DH gut) and irradiated, autologous peripheral blood
      mononuclear cells were also added. The TCL were stained for CD3, CD4, CD8, TCR
      alpha beta and gamma delta expression by indirect immunofluorescence, and their
      proliferative responses to mitogens and gluten fraction III (a peptic-tryptic
      digest of gluten) investigated. Of the eight CD3+ TCL, four were predominantly
      CD4+ (82.1-98.8%), three predominantly CD8+ (92.6-98.6%) and one TCL contained
      both 87.6% CD4+ and 95.2% CD8+ T cells, a substantial proportion of which were
      presumably double-labelled CD4+, CD8+ T cells. All eight TCL, which were almost
      exclusively TCR alpha beta +, proliferated in response to PHA whilst six out of
      the eight were stimulated by Concanavalin A. None of the TCL proliferated to
      gluten fraction III alone; however, two TCL showed increased proliferation to the
      antigen in the presence of exogenous IL-2 or IL-4 (10 U/ml) compared to cytokine
      alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734039
TI  - Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with
      insulin-dependent diabetes mellitus (IDDM).
AB  - Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new
      quantitative immunoprecipitation followed by immunoblotting assay using Chinese
      hamster ovary cells to produce recombinant human islet GAD65 and were compared
      with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell
      proteins (64K antibodies) and antibodies against GAD purified from pig brain.
      This assay showed that sensitivity and specificity were 83.3% and 100%,
      respectively. GAD65 antibodies were assayed in 32 Japanese patients with insulin
      dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent
      diabetes mellitus (NIDDM and 25 healthy volunteers. GAD65 antibodies were found
      in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17
      patients with long-term IDDM. GAD65 antibodies were detected in none of 25
      patients with NIDDM or 25 healthy volunteers. The correlation between GAD65
      antibodies and ICA, and 64K antibodies was observed to be significant (r = 0.60,
      P = 0.0003 and r = 0.47, P = 0.007, respectively). GAD65 antibodies and
      antibodies against GAD purified from pig brain correlated well (r = 0.70, P =
      0.0001). The concordance between GAD65 antibodies and ICA, 64K antibodies, and
      antibodies against GAD purified from pig brain, including GAD65 and GAD67, were
      87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. We observed that a
      quantitative immunoprecipitation followed by immunoblotting assay had high
      sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of
      GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the
      major autoantigens in Japanese patients with IDDM.

PMID- 7734040
TI  - p32, a platelet autoantigen recognized by an SLE-derived autoantibody that
      inhibits platelet aggregation.
AB  - We have previously described an SLE-derived human hybridoma autoantibody, 9604,
      which binds to activated but not to resting platelets, inhibits platelet
      aggregation, and immunoprecipitates a surface-labelled poly-peptide of 32,000
      molecular weight (MW) (p32). In the present study, using a murine monoclonal anti
      p32 antibody (8E8), we show that p32 is responsible for the binding of 9604 to
      activated platelets. First, 8E8 bound to the surface of activated but not resting
      platelets, as detected by flow cytometry, showing saturation with 1900 antibody
      molecules bound/platelet and a Kd of 72 nM. Second, complete inhibition of the
      binding of 9604 to ADP-activated platelets by 8E8 and inhibition of the
      reactivity of 8E8 with p32 by 9604 demonstrated that 8E8 and 9604 recognize the
      same 32,000 MW platelet polypeptide. Isolation of platelet proteins, using an 8E8
      affinity column, showed high MW bands corresponding to multimers of p32 under non
      reducing conditions, and isolated p32 tended to self-associate even under
      reducing conditions. High performance liquid chromatography (HPLC) demonstrated
      that the native p32-containing protein has an approximate MW of 450,000. A
      comparison of the functional properties of murine monoclonal 8E8 and human
      monoclonal 9604 revealed that both antibodies are cytotoxic to platelets in 51Cr
      release assays. In contrast, 8E8, unlike 9604, did not affect platelet
      aggregation, suggesting that different epitopes may be recognized by the two
      antibodies. These findings demonstrate that p32 is a subunit of an activation
      marker that is expressed on the surface of activated platelets and recognized by
      an SLE-derived anti-platelet autoantibody. Our data also indicate that murine
      monoclonal antibodies produced against platelet autoantigens may not mimic the
      functional activities of spontaneously occurring autoantibodies, probably due to
      the recognition of different epitopes.

PMID- 7734041
TI  - Role of humoral factors in the progression of HIV disease.

PMID- 7734042
TI  - Autoimmune versus inflammatory type I diabetes: a controversy?

PMID- 7734043
TI  - Cytokines and gene therapy.

PMID- 7734044
TI  - T-cell repertoire diversity and clonal expansions in normal and clinical samples.
AB  - Improved polymerase chain reaction (PCR)-based methods now permit a more in-depth
      analysis of the repertoire of T cells recovered in biological samples from mice
      and humans. At a certain level of resolution, the diversity of the T-cell
      repertoire can be readily estimated and clonal expansions become easily
      detectable. As discussed here by Christophe Pannetier, Jos Even and Philippe
      Kourilsky, these improvements allow a better appreciation of the degree of
      reproducibility of immune responses, both in mice and humans, and should have a
      significant impact on clinical investigations.

PMID- 7734045
TI  - The injured cell: the role of the dendritic cell system as a sentinel receptor
      pathway.
AB  - A major unresolved paradox in immunology remains: how do we avoid harm, despite
      the abundant opportunities for induction of immune responses against self
      proteins? Here, Mohammad Ibrahim, Benjamin Chain and David Katz extend Janeway's
      proposed explanation, arguing that adaptive immune responses are initiated not
      only by conserved microbial products, but also by microenvironmental tissue
      injury. They suggest that the key step is local dendritic cell activation,
      followed by upregulation of T-cell costimulatory molecules on these cells, and
      migration, leading to antigen presentation.

PMID- 7734046
TI  - Immune activation is a dominant factor in the pathogenesis of African AIDS.
AB  - The AIDS epidemic in Africa is very different from the epidemic in the West. As
      suggested here by Zvi Bentwich, Alexander Kalinkovich and Ziva Weisman, this
      appears to be primarily a consequence of the over-activation of the immune system
      in the African population, owing to the extremely high prevalence of infections,
      particularly helminthic, in Africa. Such activation shifts the cytokine balance
      towards a T helper 0/2 (Th0/2)-type response, which makes the host more
      susceptible to infection with human immunodeficiency virus (HIV) and less able to
      cope with it.

PMID- 7734047
TI  - On the nomenclature for V-region serological markers.
AB  - A recent article in Immunology Today raised significant questions concerning the
      appropriate use of the terms 'idiotype' and 'V-region isotype'. An alternative
      approach to the usage of these terms, which emphasizes their functional aspects,
      is presented here by Alfred Nisonoff.

PMID- 7734048
TI  - Perforin: structure and function.
AB  - Perforin is a cytolytic mediator produced by killer lymphocytes, and is stored in
      and released by cytoplasmic granules. The protein is partially homologous to the
      terminal components of the membrane attack complex of complement and produces
      pores of up to 20 nm in diameter on target membranes. Its genomic and protein
      structures have recently been unraveled, and its function elucidated through the
      availability of genetically engineered, perforin-deficient mice. Here Chau-Ching
      Liu, Craig M. Walsh and John Ding-E Young briefly outline certain biochemical and
      molecular features of perforin, and discuss the still-evolving issues concerning
      the relevance of perforin and Fas in cell killing.

PMID- 7734049
TI  - Granzymes: exogenous proteinases that induce target cell apoptosis.
AB  - Cytotoxic lymphocytes mediate immunity against viruses and surveillance against
      neoplastic transformation. They kill target cells by multiple mechanisms, but
      utilize a pore-forming protein, perforin, and a family of serine proteinases as
      their principal means of inflicting cell death. Recent studies have demonstrated
      that perforin and serine proteinases synergistically trigger an endogenous
      pathway of apoptosis resulting in dissolution of the target cell nuclear membrane
      and DNA fragmentation. These changes may be secondary to inappropriate activation
      of p34cdc2 kinase and the subsequent derangement of cell cycle control. As
      discussed by Mark Smyth and Joseph Trapani, the immediate molecular targets of
      perforin/granzyme-mediated apoptosis are still unclear, though candidate
      molecules with homology to cell death gene products from primitive organisms are
      currently under close scrutiny.

PMID- 7734050
TI  - Nomenclature of V-region markers.

PMID- 7734051
TI  - [Influence of the type of dietary carbohydrate on the use of 2 protein sources by
      rainbow trout reared at 8 or 18C].
AB  - The effect of the type of dietary starch (gelatinized vs native) on the
      biological value of fish meal (FP) and fish soluble protein concentrate (CPSP)
      was studied through the nitrogen balance in rainbow trout (Oncorhynchus mykiss)
      reared for 3 weeks at 2 water temperatures: 8 or 18 degrees C. The protein
      sources were included in diets at a level of 60% and gelatinized or raw starch at
      a level of 30%. Gelatinized starch improved the biological value of FP and CPSP
      by reducing the metabolic nitrogen losses. Trout fed the diet with CPSP had a
      higher nitrogen excretion than those fed the diet with FP. The biological value
      of both protein sources was unaffected by water temperature.

PMID- 7734052
TI  - [Energetic and/or nitrogen underfeeding in the dry cow. Effects on volatile fatty
      acids in the rumen, some plasma metabolites and hormones and urinary excretion of
      3-methylhistidine].
AB  - In order to study the effects of a nitrogenous and/or energetic underfeeding on
      some metabolites and hormones, 4 dry cows were fed in 2 equal daily meals with
      hay-based rations. Four rations were distributed. They supplied too much (HN) or
      too little (LN) digestible protein in the small intestine and too much (HE) or
      too little (LE) net energy, ie the diets were HN-HE, HN-LE, LN-HE, and LN-LE.
      Continuous collection of rumen liquor samples (volatile fatty acids or VFA
      determination), venous blood samples (amino acids (alanine Ala, glutamine Gln,
      glycine Gly and serine Ser), urea, glucose, insulin and growth hormone (GH)
      measurements) and urine samples (determination of the amount of 3-methylhistidine
      3-MeHi excreted) was carried out for 24 consecutive hours. By comparison with the
      reference diet (HN-HE), underfeeding was accompanied by a reduction in ruminal
      VFA concentrations, an increase in those of plasma Gly and GH, and a maintenance
      of glycemia levels. Furthermore, nitrogenous and energetic underfeeding (LN-LE)
      was accompanied by a decrease in plasma Ala, Gln and insulin concentrations.
      Nitrogenous underfeeding (LN-HE) caused a decrease in uremia levels, an increment
      in those of serinemia and no variation in circulating insulin concentrations. The
      energetic underfeeding (HN-LE) was accompanied by a reduction in insulinemia
      levels and an increase in those of alaninemia and serinemia. Such changes suggest
      that dry cattle adapt to underfeeding by mobilizing endogenous proteins. However,
      only the 2 diets with reduced energetic supplies were accompanied by an increase
      (P < 0.05) in the amount of the urinary 3-MeHi excreted per 24 h, suggesting that
      the level of energy in the diet is the main trigger for protein mobilization.
      Finally, the study of the 24-h evolution of the parameters revealed the influence
      of the feeding time (morning or evening) and the level of the dietary nitrogen
      and energy supplied on the variation in their concentration.

PMID- 7734053
TI  - Levels of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin
      (CBG) messenger ribonucleic acid (mRNAs) in ovarian endometriosis.
AB  - Recently, much evidence has indicated that sex hormone-binding globulin (SHBG)
      and corticosteroid-binding globulin (CBG) play a role in the intracellular action
      of sex steroids in target cells. In the present work, expression of SHBG mRNA and
      CBG mRNA was demonstrated in tissues of human normal endometrium and pelvic
      endometriosis, using the reverse transcription-polymerase chain reaction (RT
      PCR). SHBG mRNA levels were higher in pelvic endometriosis than in normal
      endometrium (P < 0.02), while CBG mRNA levels were lower than in normal
      endometrium (P < 0.05). The SHBG mRNA/CBG mRNA ratio was significantly higher in
      pelvic endometriosis than in normal endometrium (P < 0.01). These findings
      suggest that overexpression of intercellular SHBG in endometriotic tissues
      results in the formation of the estrogen-predominant milieu, since SHBG-bound
      estrogen is considered to be protected from the metabolism in liver and available
      in endometrial cells, thereby assisting the development of the pelvic
      endometriosis.

PMID- 7734054
TI  - Effects of dietary fat and L-methionine on the hepatic metabolism of very low
      density lipoproteins in the preruminant calf, Bos spp.
AB  - The effects of triglycerides (TG) from tallow (1.21 and 2.13 g TG/kg of body
      weight (BW) per meal, diets R and B respectively) and from tallow plus cream
      (2.50 g TG/kg of BW per meal, diet L) with or without L-methionine (2.6 g/kg dry
      matter) on hepatic apparent secretion of very low density lipoproteins (VLDL)
      were investigated in 3 groups of 4 preruminant calves fitted with chronic
      catheters and with electromagnetic blood-flow probes implanted in their hepatic
      vessels. Increasing TG concentrations stimulated the apparent VLDL secretion by
      the liver (1.02, -0.36 and -1.51 mg VLDL mass/min per kg of BW in diets L, B and
      R, respectively). L-Methionine increased this secretion when associated with the
      lipid-restricted (diet R; 0.25 and -1.51 mg VLDL/min per kg of BW) and basal
      (diet B; 0.35 and -0.36 mg VLDL/min per kg of BW) diets (non-significant).
      However, the VLDL apparent secretion decreased with the lipid-enriched diet (diet
      L), which suggests an insufficient dose of L-methionine compared with the level
      of TG intake, and a possible competition between liver and intestine for
      utilization of L-methionine for the synthesis of TG-rich lipoproteins.

PMID- 7734055
TI  - Transport of beta-lactoglobulin and alpha-lactalbumin in enterocyte-like Caco-2
      cells.
AB  - The transport of [14C]-radiolabelled beta-lactoglobulin and alpha-lactalbumin
      through Caco-2 cell monolayers grown on permeable filters was studied in order to
      evaluate the different protein pathways through the intestinal epithelium. beta
      Lactoglobulin or alpha-lactalbumin (0.25-3 mg/ml) was introduced on the apical
      side of the monolayer and both the transport and the release of labelled material
      from the cells were measured following different incubation times. The labelled
      material was analysed by either trichloroacetic acid precipitation or by high
      pressure liquid chromatography. Despite some differences between the 2 proteins,
      the overall mechanism followed approximately the same pattern. Part of the intact
      internalized protein was either recycled (10-15%) or transported via transcytosis
      (about 5%). Another pathway corresponded to the intracellular degradation of the
      protein. The calculation of the different routes followed by the proteins
      indicated that the main part of the degraded fraction (about 70%) was recycled
      whereas approximately 30% was transported to the other side. Moreover, 5-10% of
      the endocytosed material was retained intracellularly.

PMID- 7734056
TI  - Assessment of gastrointestinal permeability to small marker probes in the
      preruminant calf.
AB  - The intestinal permeability to markers was assessed in preruminant calves fed
      different milk substitutes containing skimmed milk powder or whey and soyabean
      products of differing antigenic activity as the protein sources. In Experiment 1,
      the 6 h urinary excretion of lactulose transiently decreased with the antigenic
      soyabean product but not that of sucrose of D-mannitol. In Experiment 2, the 6 h
      urinary excretion of sucrose and D-mannitol averaged 1-3%, regardless of age and
      dietary treatment. Cr-EDTA was recovered at rates of 2 and 4% after 6 and 24 h of
      urinary collection, respectively. The 24 h excretion of Cr-EDTA was lower in the
      calves fed the antigenic flour than in the controls after 2 weeks of experimental
      feeding (2.9 vs 6.0%, P < 0.05) but not thereafter. This transient decrease was
      also observed using D-xylose with the antigenic flour and with the non-antigenic
      concentrate (17 and 22% respectively vs 37%, P < 0.05). The present markers,
      including sucrose, may be suitable for assessing intestinal permeability in the
      calf even though excretion rates differed from one marker to another. Changes in
      the intestinal permeability to antigenic soya were of low magnitude and were only
      transiently detected when measured using lactulose, Cr-EDTA or D-xylose, probes
      which were therefore more sensitive than sucrose or D-mannitol.

PMID- 7734057
TI  - [Molecular mechanisms of stimulation and desensitization of Sertoli cells by
      follicle-stimulating hormone].
AB  - Many Sertoli functions are regulated by the receptor-mediated action of follicle
      stimulating hormone (FSH). The interaction of FSH with its specific cell surface
      receptors leads to stimulation of a number of intracellular events, including the
      activation of guanine nucleotide binding protein (G protein), adenylate cyclase
      and the cAMP-dependent protein kinase (PKA) pathway. In addition to positive
      regulation of cell functions, a phenomenon of refractoriness occurs after primary
      exposure of target cells to the hormone. Different sites of lesion have been
      suggested including down-regulation of FSH receptor, uncoupling of the receptor
      and the G protein/adenylate cyclase complex, and stimulation of nucleotide
      phosphodiesterases or inhibition of PKA activity. Alterations of cell
      responsiveness are mediated by a combination of these different mechanisms
      occurring over different time-scales and hormonal concentrations.

PMID- 7734058
TI  - Minamata disease: methylmercury poisoning in Japan caused by environmental
      pollution.
AB  - Minamata disease (M. d.) is methylmercury (MeHg) poisoning that occurred in
      humans who ingested fish and shellfish contaminated by MeHg discharged in waste
      water from a chemical plant (Chisso Co. Ltd.). It was in May 1956, that M. d. was
      first officially "discovered" in Minamata City, south-west region of Japan's
      Kyushu Island. The marine products in Minamata Bay displayed high levels of Hg
      contamination (5.61 to 35.7 ppm). The Hg content in hair of patients, their
      family and inhabitants of the Shiranui Sea coastline were also detected at high
      levels of Hg (max. 705 ppm). Typical symptoms of M. d. are as follows: sensory
      disturbances (glove and stocking type), ataxia, dysarthria, constriction of the
      visual field, auditory disturbances and tremor were also seen. Further, the fetus
      was poisoned by MeHg when their mothers ingested contaminated marine life (named
      congenital M. d.). The symptom of patients were serious, and extensive lesions of
      the brain were observed. While the number of grave cases with acute M. d. in the
      initial stage was decreasing, the numbers of chronic M. d. patients who
      manifested symptoms gradually over an extended period of time was on the
      increase. For the past 36 years, of the 2252 patients who have been officially
      recognized as having M. d., 1043 have died. This paper also discusses the recent
      remaining problems.

PMID- 7734059
TI  - Oxygen and xenobiotic reductase activities of cytochrome P450.
AB  - The oxygen reductase and xenobiotic reductase activities of cytochrome P450
      (P450) are reviewed. During the oxygen reductase activity of P450, molecular
      oxygen is reduced to superoxide anion radicals (O2-.) most likely by
      autooxidation of a P450 ferric-dioxyanion complex. The formation of reactive
      oxygen species (O2-., hydrogen peroxide, and, notably, hydroxyl free radicals)
      presents a potential toxication pathway, particularly when effective means of
      detoxication are lacking. Under anaerobic conditions, P450 may also be involved
      in the reduction of xenobiotics. During the xenobiotic reductase activity of
      P450, xenobiotics are reduced by the ferrous xenobiotic complex. After xenobiotic
      reduction by P450, xenobiotic free radicals are formed that are often capable of
      reacting directly with tissue macromolecules. Unfortunately, the compounds that
      are reductively activated by P450 have little structural similarity. The precise
      molecular mechanism underlying the xenobiotic reductase activity of P450 is,
      therefore, not yet fully understood. Moreover, description of the molecular
      mechanisms of xenobiotic and oxygen reduction reactions by P450 is limited by the
      lack of knowledge of the three-dimensional (3D) structure of the mammalian P450
      proteins.

PMID- 7734060
TI  - Comparative QSAR in toxicology: examples from teratology and cancer chemotherapy
      of aniline mustards.
AB  - During the past 30 years, thousands of quantitative structure-activity
      relationships (QSAR) have been published for all sorts of chemicals acting on
      many forms of life or parts thereof (DNA, enzymes, organelles, etc.). Very little
      effort has been made to show the relationship among these equations. In this
      report, we discuss two examples, the toxicity of phenols to rats and the effect
      of aniline mustards on a variety of living systems, where the electronic effects
      in the QSAR can be correlated to QSAR from physical organic chemistry. This
      enables one to make better mechanistic deductions about the biological structure
      activity relationships. From this, it is concluded that radicals formed from the
      phenols cause birth defects.

PMID- 7734061
TI  - Cell cycle disturbance in relation to micronucleus formation induced by the
      carcinogenic estrogen diethylstilbestrol.
AB  - In addition to its tumor-promoting activity in hormone-receptive tissue, the
      carcinogenic estrogen diethylstilbestrol (DES) has been found to induce cell
      transformation, aneuploidy and micronucleus formation in mammalian cells. The
      majority of these micronuclei contained whole chromosomes and were formed during
      mitosis. Here a possible relationship between a disturbance in cell cycle
      progression and micronucleus formation is investigated by exposing Syrian hamster
      embryo (SHE) cells to DES. Continuous bromodeoxyuridine labeling followed by
      bivariate Hoechst 33258/ethidium bromide flow cytometry was employed for analysis
      of cell cycle transit and related to the time course of micronucleus formation.
      Treatment of SHE cells with DES resulted in delayed and impaired cell activation
      (exit from the G0/G1 phase), impaired S-phase transit and, mainly, G2-phase
      traverse. Cells forming micronuclei, on the other hand, were predominantly in G2
      phase during DES treatment. These results suggest that impairment of S and G2
      transit may involve a process ultimately leading to micronucleus formation.

PMID- 7734062
TI  - Enhancement of Ia antigen expression and nonproliferating cells correlates with
      metastatic capacity.
AB  - Maintaining B16F10 tumor cells in stirring culture for 48 h leads to an increase
      in lung and liver colonizing capacity in comparison with cells in adherent
      culture. Parallel to the increased metastatic capacity, we have observed a
      decrease in the proliferative rate of tumor cells (as the percentage of
      proliferating cell nuclear antigen-positive cells) and an increase in the
      population of tumor cells expressing Ia antigen. These results are not exclusive
      to B16F10 cells, since the same results were obtained when we analyzed 3LL cells
      maintained in identical culture conditions. In all the tumor lines tested, we
      found an association between the nonproliferating and the Ia-positive cell
      populations. We induced Ia expression by treating B16F10 cells in adherent
      culture with the lectin concanavalin A and again, coincident with an increase in
      metastatic capacity, we found the same association between the two parameters
      analyzed--nonproliferating state and Ia antigen expression. In addition, it was
      found that B16F10 cells induce lymphocytic proliferation, and a direct
      relationship was established between the number of Ia+ cells and lymphocytic
      proliferation.

PMID- 7734063
TI  - A formalin-inactivated vaccine protects against mucosal papillomavirus infection:
      a canine model.
AB  - A formalin-inactivated canine oral papilloma homogenate was used as a vaccine to
      prevent infection by the oncogenic, mucosotropic canine oral papillomavirus
      (COPV) in beagle dogs. Twenty-six dogs received 2 doses of phosphate-buffered
      saline intradermally and 99 dogs received 2 doses of the inactivated vaccine. One
      month after the second dose all dogs were challenged with infectious COPV by
      scarification of the oral mucosa. All of the control dogs developed papillomas by
      6-8 weeks after challenge while none of the vaccinated dogs did. This vaccine has
      been used successfully in approximately 60,000 line bred beagles with no untoward
      effects and with long-lasting protection. These data demonstrate that a
      systemically administered, formalin-inactivated vaccine can protect against
      mucosal infection by COPV and suggest approaches for the development of human
      papillomavirus vaccines.

PMID- 7734064
TI  - Cell CAM 105 isoform RNA expression is differentially regulated during rat liver
      regeneration and carcinogenesis.
AB  - Cell CAM 105 (C-CAM) is a member of the carcinoembryonic antigen family and has
      been characterized as a rat hepatocyte cell-cell adhesion molecule via antibody
      activity. Two isoforms have been cloned and differ primarily in the length of the
      cytoplasmic domain. Despite extensive structural studies, little is known about
      their function and regulation in vivo. We have examined C-CAM expression during
      rat liver regeneration and hepatocarcinogenesis. Steady-state C-CAM RNA varied
      less than 3-fold during regeneration with subtle changes in the isoform ratio
      both before and after hepatocyte division. In liver tumors and transformed cells
      derived from tumors, however, large-scale decreases were observed in C-CAM RNA
      with wide variations in isoform ratios. In general, RNA decreases were reflected
      at the protein level. Our data suggest whereas down-regulation and alterations in
      C-CAM isoform ratio are transient during regulated liver growth, they are
      permanent in malignancy and may modulate hepatocyte adhesion.

PMID- 7734065
TI  - Heterosynaptic long-term facilitation of sensory-evoked responses in the auditory
      cortex by stimulation of the magnocellular medial geniculate body in guinea pigs.
AB  - The magnocellular nucleus of the medial geniculate body (MGm) develops
      physiological plasticity during classical conditioning and may be involved in
      learning-induced receptive field plasticity in the auditory cortex. To determine
      the ability of the MGm to produce long-term modification of evoked activity in
      the auditory cortex, the experimenters paired electrical stimulation of the MGm
      with preceding clicks in adult guinea pigs under barbiturate anesthesia. The
      amplitudes of average click-evoked potentials were significantly facilitated in
      all subjects. Facilitation endured for 2 hr, the maximum duration of recording.
      Sham-stimulated control guinea pigs did not develop facilitation. Thus, a
      nonlemniscal thalamic sensory nucleus can produce enduring facilitation of
      sensory-evoked activity in primary sensory cortex, suggesting that long-term
      physiological plasticity in the sensory cortex during learning may involve
      nonlemniscal thalamic mechanisms.

PMID- 7734066
TI  - Stress and consumption: inescapable shock, neophobia, and quinine finickiness in
      rats.
AB  - Exposure to inescapable shock has been shown to result in reduced consumption of
      quinine in water (the finickiness effect) in rats. In the present experiment, (a)
      a clear difference in finickiness occurred between male adult rats exposed to
      inescapable shock and those exposed to escapable shock (the first such
      demonstration), (b) finickiness was reinstated 20 days later, and (c) finickiness
      was eliminated by quinine exposure prior to treatment. The first 2 results
      support the role of uncontrollability and/or unpredictability in finickiness and
      extend its potential impact to long-term consequences. This allows greater
      potential for the modeling of long-term effects, such as eating disorders and
      depression in humans. The finding that preexposure to quinine eliminated
      finickiness is contrary to current accounts of the effect. Accounts of
      finickiness are proposed in terms of classically conditioned aversions,
      bitterness, and neuropeptide control of ingestion.

PMID- 7734067
TI  - Effect of isolation conditions on brain regional enkephalin and beta-endorphin
      levels and vocalizations in 10-day-old rat pups.
AB  - Young rat pups were isolated from their dams under different conditions. The
      endogenous opioid peptides were measured in brain regions after isolation.
      Because there is no uptake mechanism for peptides released at the synapse and
      because released peptide is rapidly degraded enzymatically, decreases in peptide
      levels over this time course can be interpreted as release from terminals. No
      change was observed in either peptide in the hypothalamus, septum, or amygdala
      after isolation compared with controls. Significant decreases were seen in the
      midbrain after isolation. A comparison of peptide levels and ultrasonic
      vocalizations in the pups isolated in familiar, novel, or control conditions was
      also performed. Enkephalin levels in the midbrain were decreased in familiar and
      novel conditions, but in the brainstem opioid peptides were decreased only in the
      familiar condition. The greater involvement of the opioid peptides in the pups
      isolated in familiar conditions may contribute to the ability of naltrexone to
      block vocalization.

PMID- 7734068
TI  - Opioids and sexual behavior of male rats: involvement of the medial preoptic
      area.
AB  - Local infusion of beta-endorphin (beta-END) into the medial preoptic area (MPOA)
      dose-dependently impaired the gating of the copulatory response and the execution
      of the sexual performance of sexually experienced, intact male rats. Local
      naloxone treatment prevented the impairment of the sexual response by beta-END,
      but failed to facilitate unimpaired copulation. Local infusion into the MPOA of
      equimolar doses of alpha-endorphin, dynorphin-A-(1-17) or met-enkephalin were
      less effective than beta-END. It is suggested that endogenous opioid systems in
      the MPOA are normally quiescent, and increased activity may be related to
      disrupted or inhibited male sexual behavior.

PMID- 7734069
TI  - Importance of pup-related sensory inputs and maternal performance for the
      expression of Fos-like immunoreactivity in the preoptic area and ventral bed
      nucleus of the stria terminalis of postpartum rats.
AB  - This study used Fos immunocytochemistry to locate neurons within the medial
      preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (VBNST) that
      are tightly associated with the performance of maternal behavior in postpartum
      rats. In the first experiment, a high degree of Fos activation was observed in
      these regions if females were allowed to interact fully with pups, but not if
      they could receive only olfactory, visual, and auditory inputs from pups. The
      second experiment found that olfactory bulbectomy combined with thelectomy did
      not eliminate Fos expression in the MPOA and VBNST of females displaying maternal
      behavior. These Fos-expressing neurons may represent efferent neurons essential
      for the performance of maternal behavior.

PMID- 7734070
TI  - Sustained potential shifts in the toad tectum reflect prey-catching and avoidance
      behavior.
AB  - Sustained potential shifts (SPS) were recorded for 10 s from the surface of the
      optic tectum of toads presented with live prey and moving artificial prey
      stimuli. On the anterior tectal surface, a negative SPS was followed by a
      positive wave; the converse was true for the posterior tectum. Some animals were
      immobilized, and they exhibited a monophasic negative SPS in the anterior tectum
      and a positive wave in more posterior regions. The number of orienting responses
      made by toads to moving "wormlike" stimuli was reflected in the amplitude of the
      SPS, as was avoidance to stimuli in an "antiworm" configuration. Behavioral
      activity was most closely related to the negativity of the SPS recording. The SPS
      of toads responding to live prey showed no direct time relationship between the
      SPS and behavior, suggesting that the SPS reflects sensory or decision-making
      activity rather than the consequent behavior.

PMID- 7734071
TI  - Abdominal vagotomy attenuates the inhibiting effect of mannitol on the ingestive
      behavior of rats.
AB  - Intact and abdominally vagotomized rats were offered for ingestion during a 30
      min period a saccharin and glucose solution or another with 0.1 M mannitol added.
      The addition of mannitol to the test solution caused a large reduction in intake
      of intact rats caused by a very rapid decline in the rate of licking during the
      test. This did not occur with the vagotomized rats. This demonstrates that
      abdominal vagal nerves are necessary for the inhibitory effect of mannitol on the
      ingestive behavior of rats. Vagotomized rats also differed from the intact ones
      by ingesting less of the mannitol-free solution. This was suggested to result
      from accelerated gastric clearance, leading to abnormally rapid stimulation of
      negative feedback from the small intestine conveyed to the CNS by extravagal
      pathways.

PMID- 7734072
TI  - Integration of free pulses in electrical self-stimulation of the rat brain.
AB  - Frequency thresholds for electrical self-stimulation of the medial forebrain
      bundle were estimated in rats while low frequencies of pulses were applied
      continuously. When continuous pulses were delivered to the same electrode that
      received the 0.5-s trains of response-initiated stimulation, thresholds decreased
      by the free-pulse frequency (Experiment 1), consistently across current
      (Experiment 2). Estimates of the reward added by concurrent, response-contingent
      stimulation of the opposite electrode of a bilateral pair predicted the drop in
      threshold caused by the noncontingent pulses applied to the opposite hemisphere
      (Experiment 3), again, robustly across test current (Experiment 4). Continuous
      pulses restricted to times between self-initiated trains lost their effect
      (Experiment 5). The perception of reward was invariant despite changes in the
      overall activity of the self-stimulation substrate.

PMID- 7734073
TI  - Age-related deficits in retention of the classically conditioned nictitating
      membrane response in rabbits.
AB  - Young and aged rabbits underwent classical conditioning of the nictitating
      membrane response (NMR) to a tone conditioned stimulus (CS) and a corneal airpuff
      unconditioned stimulus (UCS) for 18 consecutive days. Rabbits were then returned
      to their home cages for a 90-day period in which they received no further
      conditioning, but they were handled daily. On Day 91 they underwent retention
      testing during which the CS alone was presented 20 times. This was immediately
      followed by reacquisition in which the CS and UCS were again paired for 100
      trials. Reacquisition was repeated on the following day. As in previous studies,
      aged rabbits acquired the conditioned response (CR) more slowly than young
      rabbits; however, by the end of acquisition, both groups reached similar
      asymptotic levels. Retention of the CR was significantly lower for aged than
      young rabbits. Reacquisition was also retarded in aged vs. young rabbits.
      Nonassociative factors, such as sensitivity to the stimuli or general health,
      could not account for these differences. Data are discussed in terms of using
      retention of the conditioned eyeblink response as a model system for studying age
      related memory deficits.

PMID- 7734074
TI  - Spatial learning in male and female Long-Evans rats.
AB  - Male and female Long-Evans rats were tested in the Morris water maze at 6 months
      of age. A place training procedure, in which rats learned the position of a
      camouflaged platform, was followed by cue training, in which rats escaped to a
      visible platform. No sex difference was found in place learning ability. Search
      accuracy on probe trials, when the platform was unavailable, was also equivalent
      for the male and female groups. These results contrast with previous studies of
      rodents at younger ages, which have reported a male advantage in spatial
      learning. It is suggested that the age at which rats are assessed may be an
      important factor, possibly reflecting a different course in the relatively
      protracted maturation of the hippocampus in male and female rats. The results of
      this investigation are also discussed with reference to studies of sex
      differences for spatial abilities in humans.

PMID- 7734075
TI  - Septal lesions potentiate freezing behavior to contextual but not to phasic
      conditioned stimuli in rats.
AB  - The effects on freezing behavior elicited by contextual and phasic conditioned
      stimuli (CSs) were examined in rats with septal lesions. Two weeks after surgery,
      blocks of 2 conditioning trials consisting of a tone (10 kHz, 75 dB, 20 s) paired
      with a footshock (500 ms, 0.5 mA) were presented on 2 consecutive days. Tone
      alone trials were presented each day thereafter until extinction criterion was
      met. Septal lesions were found to potentiate the freezing response elicited by
      contextual stimuli but had no effect on freezing elicited by the phasic CS. The
      septum thus appears to be involved in the acquisition and/or expression of
      defensive behaviors elicited by contextual stimuli.

PMID- 7734076
TI  - Conditioning-specific modification of the rabbit's unconditioned nictitating
      membrane response.
AB  - Robust classical conditioning modifies responding to the unconditioned stimulus
      (US) in the absence of the conditioned stimulus (CS), a phenomenon the
      researchers called conditioning-specific reflex modification. Unconditioned
      responses (URs) to periorbital stimulation varying in intensity and duration were
      assessed before and after 1, 3, or 6 days of paired, explicitly unpaired, or no
      presentations of tone and electrical stimulation. After 3 days of pairings,
      conditioned responding (CRs) reached 94%, and there was an increase in latency to
      the peak of URs. The peak latency increase was replicated in a second experiment
      where rabbits reached asymptotic conditioning during 6 days of pairings. There
      was also a conditioning-specific increase in the amplitude of URs. There were no
      UR changes as a function of low level of CRs following 1 day of pairings. Data
      suggest that there are learning-specific changes in pathways mediating the US/UR,
      as well as in those mediating the CS/CR.

PMID- 7734077
TI  - Entorhinal-perirhinal lesions impair performance of rats on two versions of place
      learning in the Morris water maze.
AB  - The effects of entorhinal-perirhinal lesions in rats were studied with 2 versions
      of a place learning task in the Morris water maze. These lesions impaired
      performance on a multiple-trial task (3 days of 6 trials and a probe trial). This
      assessment was followed by a task in which rats were repeatedly trained to find
      novel locations with a variable delay (30 s or 5 min) imposed between each sample
      trial and retention test. Entorhinal-perirhinal damage produced a delay-dependent
      deficit in spatial memory: Rats with lesions were impaired at the 5-min delay
      relative to the control group and to their own performance at 30 s. These
      findings are discussed in relationship to memory impairment after entorhinal
      damage and spatial learning deficits observed after hippocampal damage.

PMID- 7734078
TI  - NMDA antagonist effects on the development of L-dopa behavioral sensitization in
      rats.
AB  - This study, which used an animal model of Parkinsonism, evaluated whether the
      NMDA antagonist MK-801 can prevent the development of L-3-4
      dihydroxyphenylalanine (L-DOPA) sensitization. In separate groups, rats with
      unilateral 6-hydroxydopamine (6-OHDA) lesions were treated with saline, 25 mg/kg
      L-DOPA methyl ester, 0.1 mg/kg MK-801, or MK-801 plus L-DOPA once per day for 13
      days beginning 18 to 20 hr postoperatively, well before the onset of denervation
      supersensitivity. Following 14 days of withdrawal, all treatment groups were
      given a saline test and on the next day, an L-DOPA challenge test. Contralateral
      rotation, the behavioral index of denervation supersensitivity, emerged on Day 7
      in both L-DOPA groups. However, on the L-DOPA challenge test, only the L-DOPA
      group showed enhanced contralateral rotations compared with a drug-naive group.
      In contrast, the MK-801 and MK-801/L-DOPA groups were indistinguishable from the
      drug-naive L-DOPA-treated rats. These findings indicate that although MK-801
      treatment did not prevent the development of behavioral sensitization to the L
      DOPA treatment, it did prevent its persistence following drug withdrawal.

PMID- 7734079
TI  - Circadian modulation in the rat acoustic startle circuit.
AB  - The acoustic startle reflex (ASR) in rats exhibits robust circadian modulation,
      with ASR amplitudes greater during subjective night. To identify the location of
      this modulation, startle reactions were evoked either acoustically or
      electrically via electrodes implanted in the primary ASR circuit. Startle
      amplitudes were compared at different times in the circadian cycle. In constant
      environmental conditions, startle amplitudes were greater in subjective night for
      acoustically evoked and for electrically evoked reactions from the ventral
      lateral lemniscus and medial longitudinal fasciculus. The results show that at
      least 1 site of circadian modulation must occur at some point in the circuit
      after the last brainstem synapse in the caudal pontine reticular formation, at
      the level of spinal interneurons or motoneurons or at the neuromuscular junction.

PMID- 7734080
TI  - Preferential use of the landmark navigational system by head direction cells in
      rats.
AB  - Previous studies have identified a population of cells recorded in the
      postsubiculum and the anterior thalamic nucleus (ATN) that discharge as a
      function of an animal's head direction (HD) in the horizontal plane. The present
      experiments monitored HD cell activity when rats were confronted with a situation
      in which directional information from internal sensory sources (e.g.,
      proprioceptive, vestibular, or motor efference copy) conflicted with directional
      information derived from familiar, external landmarks. Results showed that when a
      salient, familiar cue was reintroduced to rat's environment into a position that
      conflicted with the cell's current firing direction, HD cells in both the ATN and
      the postsubiculum shifted their preferred direction to reflect their originally
      established orientation with this cue. This finding suggests that sensory inputs
      onto HD cells from external landmark cues are capable of overriding spatial
      information developed through internal sensory cues.

PMID- 7734081
TI  - Learning and tolerance to the intake suppressive effect of cholecystokinin in
      rats.
AB  - Experiments were conducted to evaluate the contribution of conditioning to
      tolerance to the meal suppressive effect of cholecystokinin (CCK). The results
      indicate that (a) tolerance was contingent (the rat had to eat in conjunction
      with drug administration for tolerance to the meal suppressive effect to
      develop), (b) tolerance was displayed only in the context of environmental cues
      previously associated with CCK, (c) CCK-tolerant rats overate when presented with
      cues previously associated with the peptide, and (d) CCK tolerance displayed
      latent inhibition. The results are consistent with C.X. Poulos and H. Cappell's
      (1991) homeostatic theory of tolerance, as well as with the results of other
      experiments indicating that conditioning contributes to tolerance to many effects
      of a variety of drugs.

PMID- 7734082
TI  - THC-induced place and taste aversions in Lewis and Sprague-Dawley rats.
AB  - The hedonic properties of delta-9-tetrahydrocannabinol (THC) were assessed in
      place and taste conditioning paradigms in both Lewis and Sprague-Dawley rat
      strains. THC produced place avoidance, taste avoidance, and aversive taste
      reactivity responses in both strains. The Lewis strain displayed more aversive
      taste reactions and a stronger taste avoidance when conditioned with lower doses
      of THC than did the Sprague-Dawley strain of rats. THC is an anomalous drug of
      abuse that appears to be aversive to rats when assessed by these measures.

PMID- 7734083
TI  - Gustatory parabrachial lesions disrupt taste-guided quinine responsiveness in
      rats.
AB  - This study examined the effects of electrophysiologically placed electrolytic
      lesions in the gustatory zone of the parabrachial nuclei (PBN) on the rat's taste
      guided unconditioned licking of quinine hydrochloride during repeated 10-s
      trials. Concentration-response functions measured in water-deprived rats before
      and after surgery significantly shifted to the right as a result of the
      bilaterally placed lesions. These same rats were tested on their ability to
      acquire a lithium chloride (LiCl)-based conditioned taste aversion (CTA) to 0.1 M
      sucrose. Although the largest lesions severely affected performance in both
      tasks, there was only a modest correlation (r = -.447) between the extent of the
      lesion-induced shift in the quinine concentration-response curves and the degree
      of sucrose intake suppression after the first CTA conditioning trial. Thus, PBN
      lesions can disrupt performance on both tasks, but it appears that the neural
      processes governing unconditioned responsiveness to quinine may be to some extent
      dissociable from those subserving acquisition of a sucrose LiCl-based CTA.

PMID- 7734084
TI  - Neurobiology of withdrawal motivation: evidence for two separate aversive effects
      produced in morphine-naive versus morphine-dependent rats by both naloxone and
      spontaneous withdrawal.
AB  - In drug-naive rats, the rewarding effects of morphine are blocked by lesions of
      the tegmental pedunculopontine nucleus (TPP), but not by neuroleptics. In
      dependent rats (chronically treated with morphine), morphine reward is blocked by
      neuroleptics, but not by TPP lesions. Just as this activation of opiate receptors
      in naive versus dependent rats produces different mechanisms of reward, this
      study concludes that reduced opioid activity on these opiate receptors produces
      different mechanisms of aversion. Neuroleptics blocked the conditioned place
      aversions produced by naloxone and spontaneous withdrawal in morphine dependent,
      but not naive, rats, without attenuating the somatic withdrawal syndrome induced
      by naloxone in dependent rats. The researchers suggest that the aversive effects
      of endogenous opioid withdrawal in naive rats are mediated by different neural
      substrates than the aversive effects of exogenous opioid withdrawal in dependent
      rats.

PMID- 7734085
TI  - (Nitrito-O,O')bis(triphenylphosphine)-copper(I), (PPh3)2Cu(NO2-O,O').
AB  - Symmetric binding of nitrite via both O atoms to CuI [Cu--O = 2.191 (4) A] was
      observed. The copper coordination geometry is significantly distorted from
      tetrahedral, as evidenced by the angles P--Cu--P [127.75 (7) degrees] and O--Cu-
      O [56.7 (2) degrees].

PMID- 7734086
TI  - (1 beta, 5 alpha, 6 beta)-10,10- (1,2-ethylenedioxy)-1,5
      dimethylbicyclo[4.4.0]decan-4-one.
AB  - The title compound (1) [alternative name: 5,8a-dimethyl(decahydronaphthalene)-1
      spiro-2'-(1',3'-dioxolan+ ++)-6-one, C14H22O3] was obtained as the major product
      upon Pd/CaCO3-catalyzed hydrogenation of the corresponding enone (2). The
      analysis of the crystal structure of (1) has established that the monoacetal is
      cis-fused and that both rings adopt nearly perfect chair forms. The C(5) methyl
      group is in an alpha position, resulting directly from syn-hydrogenation of the
      enone. While there are two possible chair-chair conformations for cis-decalins,
      the title compound crystallized in the conformation which places the C(5) methyl
      group in an equatorial position.

PMID- 7734087
TI  - 9,11-Secogorgost-5-en-9-one-3 beta,11-diol, a marine steroid from the sea whip
      Pseudopterogorgia hummelinkii.
AB  - The title steroid [(22R,23R,24R)-22,23-methylene-23,24-dimethyl-9,11- secocholest
      5-en-9-one-3 beta,11-diol, C30H50O3], was isolated from Pseudopterogorgia
      hummelinkii, a Caribbean gorgonian. The cyclopropane ring in the side chain of
      this molecule, a feature very unusual in terrestrial steroids, has been found in
      several other marine steroids. The molecular structure is potentially very
      flexible because of the oxidative cleavage of ring C, but the two independent
      molecules in the crystal have quite similar overall conformations. The observed
      conformational differences correlate with dissimilar participation of the
      hydroxyl and carbonyl groups of each molecule in hydrogen bonding, which is
      entirely intermolecular. The crystal structure was solved by direct methods, but
      only with great difficulty.

PMID- 7734088
TI  - Tris(3,5-dimethylpyrazol-1-yl)methylsilane.
AB  - The structure consists of discrete molecules of tris-(3,5-dimethylpyrazol-1
      yl)methylsilane, C16H24N6Si, that exhibit distorted tetrahedral SiN(pyrazole)3C
      geometry about the Si atom. The Si and methyl C atoms lie on threefold axes. The
      C--Si--N and N--Si--N bond angles are 111.3 (2) and 107.5 (2) degrees,
      respectively, while the Si--N bond length is 1.745 (5) A. The present work
      provides the first reported structure containing an Si--N(pyrazole) linkage.

PMID- 7734089
TI  - Cyclic (1R,3R)-1,3-dimethyltrimethylene [(5R)-2-hydroxy-5-methyl-5-(2- methyl-1,3
      dioxolan-2-yl)-1-cyclohexen-1-yl]-phosphonate, a stable enol.
AB  - The title compound, C16H27O6P, was obtained from the rearrangement of the
      corresponding vinyl phosphate. 31P NMR experiments in solution have shown that
      this compound equilibrates to a mixture of three isomers in nearly equal
      proportions. In the crystalline state a single isomer is found which diffraction
      analysis identified as the enol form of the beta-keto phosphonate having R
      stereochemistry at atom C(8).

PMID- 7734090
TI  - Hyperinsulinemia and insulin resistance are associated with preeclampsia in
      African-Americans.
AB  - There is evidence that hyperinsulinemia and insulin resistance play a role in the
      development of hypertension. Accordingly, in our ongoing longitudinal study of
      pregnancy-induced hypertension, we have measured fasting levels of insulin and
      glucose at 18 to 25 weeks gestation in 140 nulliparous African-American women
      followed prospectively to delivery. To test the hypothesis that hyperinsulinemia
      may be related to the development of preeclampsia, discriminant analysis of mean
      arterial pressure (MAP), fasting plasma insulin levels, insulin to glucose
      ratios, and left lateral forearm vascular resistance were examined as predictors
      of preeclampsia. Statistical analysis controlled for two factors known to be
      related to insulin levels, gestational age and pregestational body mass index.
      Gestational hypertensives were not different with regard to blood pressure and
      metabolic factors from normals and thus were placed in the control group. Women
      who subsequently developed preeclampsia had mean (+/- SE) fasting plasma insulin
      levels of 51.0 +/- 12.0 microU/mL at 20 weeks and controls had values of 29.0 +/-
      2.8. Only MAP [F(4,135) = 8.8, P < .01] and insulin [F(1,135) = 6.5, P < .05]
      were related to the development of preeclampsia [F(4,135) = 4.39, R2 = 11.5%].
      The finding that elevated second-trimester insulin levels characterize the
      subsequent development of preeclampsia with control for increased MAP supports
      the hypothesis that hyperinsulinemia and associated insulin resistance may
      contribute to the pathogenesis of preeclampsia.

PMID- 7734091
TI  - Relationship of insulin, race, and hypertension with hemodynamic reactivity to a
      behavioral challenge.
AB  - Insulin is a modulator of blood pressure and may play a role in the pathogenesis
      of hypertension. This study examined the relationship between fasting insulin
      level and cardiovascular reactivity in hypertensive and normotensive black and
      white patients. Eighty-one patients were studied after 3 days of hospitalization
      on an isocaloric diet providing 200 mmol Na+ and 100 mmol K+ per day. Fasting
      insulin levels were determined on the morning of the second hospital day; a
      median split was used to determine high- and low-insulin groups. On the next day
      of hospitalization we examined blood pressure and hemodynamic responses to a
      speaking challenge. Hemodynamic responses were determined with impedance
      cardiography. Reactivity was studied as the percentage change from resting
      baseline. There were significant race by blood pressure level interactions for
      systolic and diastolic blood pressure reactivity (P < or = .01). Black
      hypertensives showed more blood pressure reactivity than either the white
      hypertensives or the white normotensives; black normotensives had less blood
      pressure reactivity than the other groups. Insulin grouping interacted with blood
      pressure level and race on the reactivity of the underlying hemodynamic measures
      (total peripheral resistance, stroke volume, and heart rate; P < or = .02).
      Fasting insulin level had no relationship to blood pressure reactivity. On the
      other hand, insulin level interacted with blood pressure level and race on the
      underlying hemodynamics controlling blood pressure, namely total peripheral
      resistance and stroke volume.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734092
TI  - Long-term stability of blood pressure and pressor reactivity to mental stress in
      borderline hypertension.
AB  - Borderline hypertension is characterized by pressor hyperreactivity to mental
      stress. However, it has not been shown whether blood pressure hyperresponsiveness
      is a temporary phenomenon due to situational anxiety or a stable feature of the
      borderline hypertensive state. We therefore evaluated the long-term stability of
      invasively assessed blood pressure and central hemodynamic responses to mental
      stress in 10 young male subjects with borderline hypertension recruited from a
      population screening. Two identical 10-min mental arithmetic stress tests were
      performed 50 to 62 months apart (median, 4 years 8 months). Intraarterial blood
      pressure was monitored continuously before, during, and after stress. Cardiac
      output was measured by the indocyanine green dye dilution technique and indexed
      for body surface area. Total peripheral resistance index was computed from
      cardiac index and mean arterial pressure. During the 4-year follow-up period,
      none of the central hemodynamic parameters had changed significantly, either with
      respect to rest or stress levels. Test-retest variability of blood pressure
      measures was low, and errors of measurement ranged between 4.8 and 8.2 mm Hg for
      blood pressure levels at rest and during stress. Mental arithmetic induced highly
      significant blood pressure increments on both occasions (ANOVA, P < .0001
      throughout). Pressor responses were somewhat but not significantly lower during
      the second test. Errors of measurement for absolute blood pressure reactivity
      ranged between 3.9 and 7.1 mm Hg. Intersession correlation coefficients for blood
      pressure levels attained during stress were above r = 0.75 throughout (P < or =
      .01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734093
TI  - Cardiac implications of the morning surge in blood pressure in elderly
      hypertensive patients: relation to arising time.
AB  - Although morning surge in blood pressure has been shown to be associated with the
      occurrence of myocardial ischemic events and stroke, few studies have been done
      regarding its pathogenesis, probably because of a lack of method for the
      quantitative assessment of awakening time. We conducted an echocardiographic
      study and ambulatory blood pressure monitoring in 23 elderly hypertensive
      patients to evaluate the relationship between the hypertensive cardiac change and
      morning surge in blood pressure. Of note was that the time of arising from bed
      was assessed quantitatively by an activetracer equipped with an internal
      acceleration sensor to monitor the physical activity. The change in systolic
      blood pressure after arising from bed was correlated significantly with the left
      ventricular mass index (r = 0.51, P < .02) and the A/E ratio, which represents
      the diastolic function (r = 0.70, P < .01). In contrast, the change in systolic
      blood pressure before rising from bed was not correlated with any
      echocardiographic parameters. We conclude that the magnitude of morning surge in
      blood pressure after arising from bed was related with the severity of
      hypertensive target organ damage.

PMID- 7734094
TI  - Postprandial intestinal-derived chylomicron and chylomicron remnants in essential
      hypertensive patients before and after prolonged captopril therapy.
AB  - The metabolism of the postprandial intestinal-derived lipoproteins, chylomicron
      and chylomicron remnants, is not known in patients with essential hypertension.
      After a fat meal, using the vitamin A test as a marker, retinyl palmitate was
      measured in the total plasma, chylomicron, and chylomicron remnant fractions in
      14 untreated nondiabetic essential hypertensive patients with normal fasting
      lipids and lipoproteins. The vitamin A fat loading test was repeated in eight
      hypertensive patients after 3 months of captopril therapy. Fifteen matched
      normotensive subjects were used as controls. The untreated essential hypertensive
      patients had significantly higher chylomicron fraction concentration curves (AUC
      17,469 +/- 2553 micrograms/L/h) P < .001 compared with the control group (AUC
      13,208 +/- 1245 micrograms/L/h), by two-way analysis of variance with repeated
      measurements. After 3 months of captopril therapy, the chylomicron fraction (AUC
      9701 +/- 1566 micrograms/L/h), and chylomicron remnants fraction (AUC 3487 +/-
      580 micrograms/L/h) were much lower (P < .001) than before captopril therapy.
      Oral glucose tolerance tests were borderline in five of the eight hypertensives
      before captopril treatment but returned to normal after 3 months of therapy. In
      summary, postprandial intestinal-derived lipoprotein metabolism is altered in
      essential hypertensive patients. Captopril therapy caused significant improvement
      in the postprandial chylomicron metabolism.

PMID- 7734095
TI  - Circulating endothelin-1 levels in lean non-insulin-dependent diabetic patients.
      Influence of ACE inhibition.
AB  - To evaluate the effect of captopril on plasma endothelin-1 (ET-1) levels and
      insulin sensitivity, 15 lean normotensive men (51.6 +/- 3.8 years) affected by
      non-insulin-dependent diabetes mellitus (NIDDM) underwent 2-h euglycemic
      hyperinsulinemic clamp. Each patient was then assigned to receive either
      captopril (25 mg twice daily for 1 week) or placebo, in a double-blind randomized
      fashion, before repeating clamp. At baseline, plasma ET-1 levels were 0.77 +/-
      0.25 pg/mL in captopril (n = 10) and 0.83 +/- 0.3 pg/mL in placebo patients (n =
      5). A twofold increase in plasma ET-1 levels occurred during the 2-h insulin
      infusion in both groups (P < .05 after 60 and 120 min), with a rapid return to
      baseline after 30 min from insulin withdrawal. After 1 week of therapy, total
      glucose uptake significantly increased in captopril (from 3.71 +/- 1.70 mg/kg/min
      to 4.24 +/- 1.72 mg/kg/min, P < .03) but not in placebo patients. Plasma ET-1
      levels significantly decreased after captopril therapy (0.48 +/- 0.25 pg/mL at
      time 0, P < .03 v pretreatment levels), but were unaffected by placebo. Moreover,
      captopril slightly reduced the magnitude of ET-1 increment during insulin
      infusion (0.65 +/- 0.28 pg/mL and 0.88 +/- 0.48 pg/mL at 60 and 120 min,
      respectively, P < .05 v time 0). As a consequence, during the second insulin
      infusion circulating ET-1 levels were significantly lower in captopril- than in
      placebo-treated patients at time 0 (P < .02), 60 (P < .002), 120 (P < .004), and
      150 min (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734096
TI  - Increased basal arterial smooth muscle glucose transport in the Zucker rat.
AB  - Insulin has recently been reported to stimulate glucose transport in vascular
      smooth muscle cells (VSMC). This observation suggests a role for this hormone in
      hypertension associated with insulin resistance. To determine whether VSMC
      glucose transport abnormalities exist in a state of insulin resistance, we
      studied basal and insulin-stimulated glucose transport in VSMC derived from
      Zucker lean (normotensive, insulin sensitive) and obese (hypertensive, insulin
      resistant) rats. Basal glucose transport, as measured by tracer quantities of
      [3H]2-deoxyglucose, was 4.2 +/- 0.8 and 7.4 +/- 0.9 fmol/10(6) cells/min for lean
      and obese cells, respectively (P < .05). Kinetic analyses utilizing variable
      concentrations of unlabeled 2-deoxyglucose in the media revealed that increased
      transport in the obese rat was due to an increased Vmax of the transporter
      system: Vmax = 5.9 +/- 0.8 and 12.1 +/- 1.2 fmol/10(6) cells/min for lean and
      obese cells, respectively (P < .05); no changes in Km were noted for the two
      populations: Km = 1.14 +/- 0.24 and 0.96 +/- 0.10 mmol/L. Insulin (10 microU/mL)
      increased the Vmax of the transporter in both preparations, but greater
      stimulation was seen in the lean VSMC: 32 +/- 4.8% v 11.5 +/- 2.1% (P < .05).
      Insulin had no effect on the Km of the transporter in either strain. These data
      suggest that increased basal glucose transport in obese VSMC may predispose the
      vessel to increased glucose-mediated events, while blunted insulin-stimulated
      glucose transport in these cells mirrors insulin-resistant glucose disposal in
      other tissues of the obese rat.

PMID- 7734097
TI  - Digitalis-like factor and digoxin-like immunoreactive factor in diabetic women
      with preeclampsia, transient hypertension of pregnancy, and normotensive
      pregnancy.
AB  - An endogenous sodium pump inhibitor, or digitalis-like factor (DLF), has been
      postulated to mediate essential hypertension. It may also play a role in
      preeclampsia. However, studies of this factor in hypertensive pregnancy have not
      provided consistent findings. Part of this may be due to the absence of
      subclassification of pregnant women with pregnancy-induced hypertension (PIH)
      when assessing these parameters. In this study we explored serum DLF and digoxin
      like immunoreactive factor (DLIF) in insulin-dependent diabetic (IDDM) women with
      normotensive pregnancies or PIH, comparing them to each other and to nondiabetic
      pregnant women. Our results demonstrated that nondiabetic women with preeclampsia
      (PE, PIH with proteinuria) had significantly increased serum DLF and DLIF
      compared to normotensive pregnant women (NL BP). Women with transient
      hypertension of pregnancy (THP, PIH without proteinuria) had intermediate values
      (DLF. NL BP: 3.3 +/- 0.6, THP: 4.8 +/- 1.1, PE: 7.6 +/- 1.3% inhibition [Na,K]
      ATPase, P < .05 ANOVA; DLIF. NL BP: 0.22 +/- 0.02, THP: 0.28 +/- 0.03, PE: 0.35
      +/- 0.02 ng digoxin equivalents/mL, P < .05 ANOVA). Pregnant normotensive IDDM
      women had significantly higher serum DLF and DLIF activity than their nondiabetic
      counterparts (DLF. non-IDDM NL BP: 3.3 +/- 0.6 v IDDM NL BP: 8.8 +/- 1.2%
      inhibition [Na,K]-ATPase, P = .0008; DLIF. non-IDDM NL BP: 0.22 +/- 0.02 v IDDM
      NL BP: 0.31 +/- 0.02 ng digoxin equivalents/mL, P = .005).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7734098
TI  - Comparison of effects of ACE inhibition with calcium channel blockade on renal
      disease in a model combining genetic hypertension and diabetes.
AB  - The aim of this study was to compare the renal effects of angiotensin converting
      enzyme (ACE) inhibition with calcium channel blockade in a model combining
      genetic hypertension with diabetes. Streptozotocin diabetes was induced in
      spontaneously hypertensive rats (SHR). The animals were then randomized to
      receive no treatment, the ACE inhibitor, perindopril, or the dihydropyridine
      calcium antagonist lacidipine. Body weight, systolic blood pressure, glycemic
      control, renal function, and albumin excretion rate (AER) were assessed serially
      over the 32-week study period. At week 32 the animals were killed and glomerular
      volume was measured. Both antihypertensive regimens significantly reduced
      systolic blood pressure in diabetic SHR. There was no significant difference in
      glycemic control, serum creatinine, or glomerular filtration rate among the three
      groups at week 32. The ACE inhibitor perindopril significantly reduced AER and
      glomerular hypertrophy over the 32 weeks, whereas the calcium antagonist
      lacidipine failed to reduce AER or glomerular hypertrophy. Thus, in contrast to
      the effects of ACE inhibition, calcium channel blockade with lacidipine, despite
      significantly reducing blood pressure, failed to reduce renal injury in this
      model. These results support the hypothesis that antihypertensive regimens may
      differ in their capacity to protect the diabetic kidney, despite similar effects
      on systemic blood pressure.

PMID- 7734099
TI  - In vivo pharmacology of a novel AT1 selective angiotensin II receptor antagonist,
      MK-996.
AB  - MK-996, N-(4'-(5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridin-3-yl- methyl)1,1'
      biphenyl-2-yl)-sulfonylbenzamide, is a potent, orally active, highly selective,
      nonpeptide angiotensin II (AII) receptor antagonist. MK-996 prevents the pressor
      response to intravenous AII in the conscious rat, dog, and rhesus monkey (ED50,
      mg/kg; oral/intravenous = 0.067/0.014, 0.035/0.017, and 0.1/0.036, respectively).
      In the anesthetized chimpanzee, MK-996 (1 mg/kg, iv) produces 100% (peak)
      inhibition of the AII pressor response and is still active (52%) at 24 h. To our
      knowledge this pharmacologic profile in the rat, dog, rhesus monkey, and
      chimpanzee presents the least species variability of any AII receptor antagonist
      yet described. Responses to methoxamine and arginine vasopressin are not affected
      by MK-996. In aortic coarcted (high renin) rats, MK-996 (3 mg/kg, by mouth)
      reduces blood pressure to normotensive (< 120 mm Hg) levels without reflex
      tachycardia. This dose of MK-996 reduces blood pressure to approximately the same
      level as both losartan (3 mg/kg, by mouth) and enalapril (3 mg/kg, by mouth) in
      this model. The duration of antihypertensive activity of MK-996 is similar to
      enalapril and shorter than losartan at the doses tested. Additionally, in the rat
      MK-996 does not potentiate the vasodepressor response to bradykinin and
      completely prevents the ability of AII to stimulate an increase in plasma levels
      of aldosterone. Therefore, MK-996 is a potent, orally active, nonpeptide AII
      receptor antagonist with a long duration of action, little species variability,
      and anti-hypertensive activity.

PMID- 7734100
TI  - Development of structural vascular changes with subpressor angiotensin II
      administration in rats.
AB  - We investigated whether the slow pressor action of small doses of angiotensin II
      (ANG II) administered to rats was accompanied by the development of structural
      vascular changes. Male Sprague-Dawley rats (350 to 400 g) were given ANG II
      intraperitoneally, 200 ng/kg/min, for 7 to 10 days or 6 weeks, or 100 ng/kg/min
      for 6 weeks. Sham-treated rats were controls. Lumen and external diameters of
      arterioles (30 to 60 microns) and small (61 to 120 microns) and intermediate-size
      (121 to 220 microns) arteries were measured in maximally dilated, pump-perfused
      (55 to 60 mm Hg), in situ fixed mesenteric and renal vascular beds, and wall-to
      lumen ratios were calculated. Systolic blood pressure and vessel dimensions were
      unchanged in rats receiving ANG II for 7 to 10 days. Systolic blood pressures
      rose (P < .001) in rats treated with 200 or 100 ng/kg/min ANG II for 6 weeks but
      were significantly different from those of controls only in rats receiving the
      higher dose (P < .01). In rats treated with 200 and 100 ng/kg/min ANG II for 6
      weeks, wall-to-lumen ratios of mesenteric and renal arteries were increased 23%
      and 9% (P < .001) and 13% and 6% (P < .01), respectively. With the higher dose of
      ANG II, the increase of wall-to-lumen ratios of mesenteric arteries was greater
      than that of renal arteries (P < .005). Initially subpressor doses of ANG II,
      when applied long enough, may lead to the development of structural vascular
      changes. There may be significant regional differences in the extent of
      structural vascular changes induced by ANG II.

PMID- 7734101
TI  - Effect of green tea rich in gamma-aminobutyric acid on blood pressure of Dahl
      salt-sensitive rats.
AB  - gamma-Aminobutyric acid (GABA) is known to be involved in the regulation of blood
      pressure by modulating the neurotransmitter release in the central and peripheral
      sympathetic nervous systems. This study investigated the antihypertensive effect
      of green tea rich in GABA (GABA-rich tea) in young and old Dahl salt-sensitive
      (S) rats. GABA-rich tea was made by fermenting fresh green tea leaves under
      nitrogen gas. In experiment 1, 21 11-month-old rats, fed a 4% NaCl diet for 3
      weeks, were given water (group W), an ordinary tea solution (group T), or a GABA
      rich tea solution (group G) for 4 weeks. The average GABA intake was 4.0 mg/rat
      per day. After 4 weeks of the treatment, blood pressure was significantly
      decreased in group G (176 +/- 4; P < .01) compared with group W (207 +/- 9) or
      group T (193 +/- 5 mm Hg). Plasma GABA levels were more elevated in group G (111
      +/- 54) than in group W (not detectable) or group T (14 +/- 8 ng/mL; P < .01 v
      G). In experiment 2, 21 5-week-old rats, fed a 4% NaCl diet, were divided into
      groups W, T, and G. The average GABA intake was 1.8 mg/rat per day. Body weight
      or chow and beverage consumption did not differ significantly among the three
      groups. After 4 weeks of the treatment, although blood pressure was comparable in
      groups W and T (165 +/- 3 v 164 +/- 5 mm Hg, mean +/- SE), it was significantly
      lower in group G (142 +/- 3 mm Hg) than in the other groups (P < .01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7734102
TI  - Effect of alcohol consumption versus abstinence on 24-h blood pressure profile in
      normotensive alcoholic patients.
AB  - The aim of this study was to evaluate 24-h ambulatory blood pressure monitoring
      in 15 male alcoholic normotensive subjects during alcohol consumption and
      following an abstinence phase and the effects of alcohol consumption compared
      with a period of 1 week of abstinence. The average 24-h BP was not different, but
      the diurnal pattern showed a fall in systolic BP early (06:00 to noon; P < .005)
      and late (18:00 to 22:00; P < .002) in the day during abstinence. BP variability
      was increased during the alcohol phase (P < .05). This study showed that 1 week
      of abstinence does not influence 24-h BP levels in normotensive subjects, but
      alters the diurnal pattern, characterized by a fall in systolic BP and increased
      BP variability.

PMID- 7734103
TI  - Platelet membrane fluidity and platelet membrane lipid pattern in essential
      hypertension.
AB  - In a group of subjects with essential hypertension platelets were studied in
      resting conditions: platelet membrane fluidity was measured with the fluorescent
      probe 1.4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH), platelet membrane
      cholesterol/phospholipid ratio was evaluated separating the membrane lipids with
      column chromatography, and platelet membrane individual phospholipids were
      determined using two-dimensional thin-layer chromatography. From the obtained
      results, it is evident that platelet membrane fluidity does not differentiate
      normals from hypertensives; platelet membrane cholesterol/phospholipid ratio is
      increased in hypertensives, while of the platelet membrane individual
      phospholipids, only the phosphatidylcholine is increased. In normals and
      hypertensives, no relation is evident between platelet membrane fluidity,
      platelet membrane lipid pattern, and systolic and diastolic blood pressure
      values.

PMID- 7734104
TI  - Sustained blood pressure control with controlled-release isradipine.
AB  - The efficacy and safety of different doses of a new controlled release
      formulation of isradipine (isradipine-CR, ICR) were evaluated in patients with
      mild to moderate (stages 1 and 2) essential hypertension in a placebo-controlled
      study. Of 402 randomized patients, 384 completed the study (placebo = 77, 5 mg
      ICR = 76, 10 mg ICR = 76, 15 mg ICR = 78, 20 mg ICR = 77). All doses of ICR
      decreased the blood pressure and the effect was greater with doses of 10, 15, and
      20 mg once daily (P < .001). The most common clinical side effect was mild ankle
      edema, which was dose dependent, occurring in 35.5% of the patients taking the 20
      mg ICR dose. This study showed that ICR is long acting, effective, and well
      tolerated.

PMID- 7734105
TI  - Segment-specific effect of chloride channel blockade on rat renal arteriolar
      contractile responses to angiotensin II.
AB  - Experiments were performed to determine the effect of a chloride channel blocker
      (indanyloxyacetic acid, IAA-94) on renal arteriolar vasoconstrictor responses to
      angiotensin II (AngII). The in vitro blood-perfused juxtamedullary nephron
      technique was exploited to provide access to the renal microvasculature of
      enalaprilat-treated rats. Under control conditions, 1 to 100 nmol/L AngII evoked
      concentration-dependent afferent arteriolar vasoconstriction. Baseline diameter
      of afferent arterioles was not altered by 30 mumol/L IAA-94; however, AngII
      responsiveness was markedly attenuated. The afferent response to K-induced
      depolarization was sustained in the presence of IAA-94. In efferent arterioles,
      neither baseline diameter nor AngII responsiveness was altered by IAA-94. These
      results suggest that full expression AngII-induced afferent (but not efferent)
      arteriolar vasoconstriction requires participation of chloride channels, which
      likely engender depolarization and subsequent opening of voltage-gated calcium
      channels.

PMID- 7734106
TI  - Angiotensin I converting enzyme (ACE) gene polymorphism and essential
      hypertension in Japan. Ethnic difference of ACE genotype.
AB  - A polymorphism of the angiotensin I converting enzyme (ACE) gene has recently
      been reported and analysis of this polymorphism has indicated that it is
      associated with several cardiovascular diseases. However, the results are still
      controversial and such association has not yet been established conclusively. To
      determine whether the ACE gene may be responsible for essential hypertension in a
      Japanese population, we also compared the distribution of genotypes and the
      allele frequency of this polymorphism in our findings of a Japanese population
      with these features in other countries. Eighty-seven hypertensive patients with a
      family history of essential hypertension and 95 normotensive patients whose
      parents had no such history were enrolled in the study. Polymorphism of the ACE
      gene was determined by using the polymerase chain reaction. Homozygotes for this
      polymorphism had either a 490-bp band (II) or a 190-bp band (DD) and
      heterozygotes had both bands (ID). In hypertensive subjects, the numbers and
      frequency of the ACE genotypes were: II, 44 (0.51); ID, 26 (0.30); DD, 17 (0.19).
      In normotensive subjects these were: II, 35 (0.37); ID, 43 (0.45); DD, 17 (0.18).
      There were no significant differences between the two groups in derived allele
      frequencies (chi 2 = 1.41). The difference between the overall allelic frequency
      in Japan and that reported in several other countries was significant. We did not
      find any association between ACE gene polymorphism and essential hypertension in
      Japan. However, there were significant differences in derived allele frequencies
      between our findings in a Japanese population and those reported from Europe and
      Australia.

PMID- 7734107
TI  - Duration of cough following cessation of ACE inhibitor therapy.

PMID- 7734108
TI  - Uptake of a neurotoxin-candidate, (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinoline into human dopaminergic neuroblastoma SH-SY5Y cells by
      dopamine transport system.
AB  - Uptake of catechol isoquinolines to dopamine cells was studied using human
      dopaminergic neuroblastoma SH-SY5Y cells. Only (R)-1,2-methyl-6,7-dihydroxy
      1,2,3,4-tetrahydroisoquinoline [(R)-1,2-DiMeDHTIQ] was transported by dopamine
      uptake system, while (S)-1,2-DiMeDHTIQ, (R)- and (S)-1-methyl-6,7-dihydroxy
      tetrahydroisoquinoline, and 1,2-dimethyl-6,7-dihydroxyisoquinolinum ion were not.
      Kinetical study showed that the uptake of (R)-1,2-DiMeDHTIQ followed the
      Michaelis-Menten equation, and the values of the Michaelis constant and the
      maximal velocity were obtained to be 102.6 +/- 36.9 microM and 66.0 +/- 2.8
      pmol/min/mg protein. Dopamine was found to inhibit (R)-1,2-DiMeDHTIQ uptake
      competitively. These results suggest that the selective uptake by dopamine
      transporter may account for the specific neurotoxicity of (R)-1,2-DiMeDHTIQ to
      dopamine neurons.

PMID- 7734109
TI  - Behavioral and frontal cortical metabolic effects of apomorphine and muscimol
      microinjections into the mediodorsal thalamic nucleus.
AB  - To study sensorimotor correlates of dopamine (DA) and gamma-amino butyric acid
      (GABA) neurotransmission in the thalamus, we microinjected the DA agonist
      apomorphine (APO), the GABA agonist muscimol and vehicle into the mediodorsal
      thalamic nucleus (MdT) of rats and monitored catalepsy, sensorimotor asymmetries
      and the acoustic startle response. Unilateral MdT muscimol microinjections (50
      ng) produced a lateralization of the removal of adhesive disks placed
      simultaneously on both forelegs in a tactile extinction task, but did not
      measurably influence any aspects of startle behavior. The sensorimotor asymmetry
      consisted of perferential orientation to the adhesive disk on the side
      ipsilateral to the microinjection. Vehicle and APO microinjections produced no
      significant behavioral results. In a follow-up study, unilateral MdT muscimol
      microinjections significantly depressed medial prefrontal cortical metabolism
      (measured by 2-fluorodeoxyglucose uptake) by 24%, but did not affect nucleus
      accumbens metabolic activity. Together, these findings are consistent with the
      concept that GABA-mediated inhibition of thalamocortical neurons in the MdT
      influences tactile extinction behavior, most likely by selectively suppressing
      excitatory input to the frontal cortex. The sensorimotor asymmetry observed in
      the present study resembles attentional and spatial memory deficits associated
      with frontal cortical lesions, and in conjunction with the 2-fluorodeoxyglucose
      results, suggests that elevated GABA neurotransmission in the thalamus may be
      involved in attentional and functional metabolic deficits in humans.

PMID- 7734110
TI  - Acceleration of desipramine-induced changes on the dopamine receptor-coupled
      adenylate cyclase system by pertussis toxin.
AB  - The response of adenylate cyclase to GTP and to dopamine (DA) was investigated in
      striatal membranes from desipramine (DMI)-treated rats (10 mg/kg, b.i.d., for 5
      days). GPT exerted the same biphasic effect on basal and DA-stimulated enzyme
      activity in membranes from DMI-treated rats as on saline-treated rats. Rats were
      injected intraventricularly once with islet activating protein (IAP), pertussis
      toxin, and given extended treatment with DMI in order to study the effects on the
      inhibitory GTP-binding protein (Gi). Gi loses its function as a signal transducer
      on being ADP-ribosylated selectively by the IAP. D2 inhibition of adenylate
      cyclase by DA was attenuated by the IAP treatment in both DMI-and saline-treated
      rats; peak levels of DA plus GTP stimulation shifted from 1 microM to 100 microM
      GTP. D1 stimulation of adenylate cyclase by DA was also attenuated by the IAP in
      the DMI-treated rats. Since long-term treatment with DMI (15 mg/kg, once a day,
      for 3 weeks) resulted in suppression of D1 stimulation similar to that seen in
      the present findings, uncoupling between D2 receptors and Gi due to IAP treatment
      might accelerate DMI-induced adaptive changes of dual control of adenylate
      cyclase system by DA.

PMID- 7734111
TI  - Homocysteinemia and schizophrenia as a case of methylation deficiency.
AB  - A 27-year-old woman is described whose disorder meets the DSM-III-R criteria for
      a diagnosis of schizophrenia and who was found to have a significantly increased
      serum level of homocysteine. Repeatedly, she improved on frequent cobalamin
      injections and deteriorated in periods without treatment. The effects of
      prolonged weekly treatment appeared to diminish as time went on, suggesting that
      the abnormality was not wholly cobalamin-dependent. It was found that
      methylenetetrahydrofolate reductase (MR) activity in cultured skin fibroblasts
      was reduced to a magnitude that is found among people with heterozygous
      deficiency. A defect in MR activity indicates a deficiency in
      methyltetrahydrofolate (MTHF), with a consequent reduction of the remethylation
      of homocysteine to methionine. Thus, reduced methylation may explain the
      increased levels of homocysteine and the transient effects of cobalamin treatment
      in the patient. Theoretically, MTHF should be the optimal treatment for her. The
      case reported highlights the importance of assessing the serum homocysteine level
      in order to detect methylation deficiency in patients with schizophrenia.

PMID- 7734112
TI  - Triplet repeats in clinical subtypes of schizophrenia: variation at the DRPLA (B
      37 CAG repeat) locus is not associated with periodic catatonia.
AB  - Clinical evidence for a dominant mode of inheritance and anticipation in periodic
      catatonia, a distinct subtype of schizophrenia, indicates that genes with triplet
      repeat expansions or other unstable repetitive elements affecting gene expression
      may be involved in the etiology of this disorder. Because patients affected with
      dentatorubral-pallidoluysian atrophy (DRPLA) may present with "schizophrenic"
      symptoms, we have investigated the DRPLA (B 37 CAG repeat) locus on chromosome 12
      in 41 patients with periodic catatonia. The B 37 CAG repeat locus was highly
      polymorphic but all alleles in both the patient and control group had repeat
      sizes within the normal range. We conclude that variation at the DRPLA locus is
      unlikely to be associated with periodic catatonia. The evidence for dominant
      inheritance and anticipation as well as the high prevalence of human brain genes
      containing trinucleotide repeats justifies further screening for triplet repeat
      expansions in periodic catatonia.

PMID- 7734113
TI  - Acute and chronic losartan administration: effect on angiotensin II content and
      modulation of [3H]norepinephrine release from rat interscapular brown adipose
      tissue.
AB  - To determine if acute or chronic (21 days) losartan (10 mg/kg, s.c.) regulates
      the renin-angiotensin system in interscapular brown adipose tissue, angiotensin
      II (AII) content and [3H]overflow from slices preloaded with [3H]norepinephrine
      were examined. Acute or chronic losartan administration had no effect on AII
      content. AII increased evoked [3H] overflow from slices from control rats.
      Losartan administration did not alter basal [3H]outflow or evoked [3H]overflow.
      Acute losartan administration inhibited AII-induced enhancement of evoked
      [3H]overflow. Tolerance developed to the inhibitory effect of losartan following
      chronic administration.

PMID- 7734115
TI  - 2nd CEC workshop on bioelectronics. Frankfurt/Main, Germany, November 1993.

PMID- 7734114
TI  - Circumscribed malformation and nerve cell alterations in the entorhinal cortex of
      schizophrenics. Pathogenetic and clinical aspects.
AB  - A postmortem histological comparison of 5 selected cases of schizophrenia with 5
      non-schizophrenic controls showed a circumscribed malformation of the entorhinal
      cortex. The cortical alterations consisted mainly of a lack or a change of the
      characteristic island formations in layer II pre-alpha. Further, there were
      atypical neurons in layers II and III showing a conspicuous decrease of volume,
      often a change of the shape. They lay either in clusters or in columnar
      formations. These cells were considered "young neurons". The changes varied
      considerably from case to case and sometimes extended to all entorhinal layers.
      In one case the extension of the changes is described by means of serial sections
      in steps which extend over the whole rostral entorhinal region. Here, the
      striking architectural changes were formed in an exactly circumscribed sector and
      did not extend to the rostral hippocampal formation. On the whole, the changes
      are regarded as local migrational disturbances that occur during the second
      trimester of brain development. Neuronal displacements like these could give rise
      to various aberrant connections within the limbic system and related structures
      (e.g. the central position of the entorhinal region in circuits such as the
      entorhino-hippocampal loop, entorhinol-insula and entorhino-orbitofrontal
      reciprocal connections). Whereas alterations of the genetic programming of cell
      migrations may be suspected, various environmental influences (e.g. viral
      infections during the months III-V of pregnancy) appear to play a significant
      role. The malformations may be a decisive vulnerability factor for the later
      manifestation of the illness.

PMID- 7734116
TI  - Clinical diagnostics opportunities for biosensors and bioelectronics.
AB  - The clinical diagnostic market represents a unique opportunity for the
      introduction of biosensors on a widespread commercial basis. To date, however,
      very few successful biosensors have been launched in this field or any other,
      despite many promising ideas. The need for biosensors in this field must be
      analyzed more critically, to assess in which direction the developing biosensor
      technology can be most effectively aimed and which areas need a more focused
      approach from basic research in bioelectronics. The diagnostics market is already
      a highly competitive field; from an industrial perspective, some of the critical
      issues that need to be taken into consideration when evaluating biosensor
      projects are: costs per test, regulatory requirements, quality control,
      instrumentation design, and test parameter selection.

PMID- 7734117
TI  - From neural chip and engineered biomolecules to bioelectronic devices: an
      overview.
AB  - At the first C.E.C. Workshop, in Brussels on 28-29 November 1991, attended by
      over 70 leading European scientists and industrialists, bioelectronics was
      defined as 'the use of biological materials and biological architectures for
      information processing systems and new devices'. At the end of the Frankfurt
      Workshop, bioelectronics, specifically bio-molecular electronics, was described
      as 'the research and development of bio-inspired (i.e. self-assembly) inorganic
      and organic materials and of bio-inspired (i.e. massive parallelism) hardware
      architectures for the implementation of new information processing systems,
      sensors and actuators, and for molecular manufacturing down to the atomic scale'.
      The subject of this overview is to summarize some of the most significant
      progress in bio-molecular electronics from neural VLSI networks and bio-molecular
      engineering. As an example of one possible route, emphasis is placed on the
      results recently obtained within this laboratory.

PMID- 7734118
TI  - 3D neuro-electronic interface devices for neuromuscular control: design studies
      and realisation steps.
AB  - In order to design the shape and dimensions of new 3D multi-microelectrode
      information transducers properly, i.e. adapted to the scale of information
      delivery to and from peripheral nerve fibres, a number of studies were, and still
      are, being performed on modelling and simulation of electrical volume conduction
      inside and outside nerves, on animal experiments on stimulation and recording
      with single wires and linear arrays, and on new technologies for 3D micro
      fabrication. This paper presents a selection of the results of these
      "Neurotechnology' studies at the University of Twente. The experimental and
      simulation results apply primarily to the peripheral motor nerves of the rat, but
      are also of interest for neural interfacing with myelinated nerves in man, as
      fascicles in man are about the same size as in the rat.

PMID- 7734119
TI  - Engineering the right membranes for electrodes at the biological interface;
      solvent cast and electropolymerised.
AB  - A generic approach to adapting many sensors to the rigours of biomedical
      measurement is to protect appropriate components with selective solute
      discriminating membrane layers. Our work has utilised external barrier membranes
      for mass transport control to enzyme electrodes in order to adapt their behaviour
      to requisite clinical ranges; these membranes have had the additional important
      effect of reducing surface deposition of colloid and other material on electrode
      surfaces. Internal membranes, especially those interposed between the enzyme
      layer and the working electrode of an amperometric sensor, have been found by us
      to be remarkably important in determining sensor operational stability. This
      paper will review such membrane materials, including coating technologies, and
      suggest appropriate directions for future work.

PMID- 7734120
TI  - Self-organising sensory maps in odour classification mimicking.
AB  - A system for artificial olfaction is introduced, which is composed of a sensor
      array for gas sensing and a self-organising artificial neural network. A detailed
      reformulation of the most effective Self-Organising sensory Map (SOM)-based
      algorithms for odour classification and other applications is provided. An opto
      electronic micromachined implementation of the neural network is introduced,
      which employs a novel hybrid mechanism for activating neural groups, avoiding
      fabricated cloning templates hardware.

PMID- 7734121
TI  - Incorporation of sulphonated cyclodextrins into polypyrrole: an approach for the
      electro-controlled delivering of neutral drugs.
AB  - The electro-controlled delivery of drugs based on the doping-dedoping mechanism
      of Electro-Conducting Polymers is restricted to charged substances acting as
      dopants. In order to overcome this limitation, this study presents an approach
      where the trapping/delivering is based on host-guest interaction. As an example
      of a neutral guest, the molecule N-methylphenothiazine (NMP) is encapsulated in
      the host, heptasulphonated beta-cyclodextrin (beta-CDSO3-), which is tailor-made
      to dope PPy. The original synthetic method for beta-CDSO3- is based on
      sulphonation of the periodated beta-CD in the phase transfer medium. As a
      consequence of their size and of their multicharged character, beta-CDSO3-s are
      fixed dopants. The stability of the beta-CDSO3- entrapment is checked by Optical
      Beam Deflection (mirage effect) measurements. The ionic movements associated with
      the switching of the beta-CDSO3- doped PPy (PPy+, beta-CDSO3-) film appear to be
      mainly due to cations with this technique. Cyclic voltammetry experiments confirm
      the entrapment of neutral NMP by simply dipping the PPy+, beta-CDSO3- film in a
      CH3CN solution containing NMP. Repeated electrochemical cycling of such a
      reservoir electrode indicates the progressive elimination of NMP from the (PPy+,
      beta-CDSO3- [NMP]) film.

PMID- 7734122
TI  - Bioelectric and microcirculation cutaneous sensors for the study of vigilance and
      emotional response during tasks and tests.
AB  - Bioelectronic phenomena related to the activity of the Autonomic Nervous System
      (ANS) activity mainly take place in the deep part of the brain where they are
      difficult to record. The hand skin, being richly innervated by sympathetic
      efferent fibres, offers an interface from which relevant ANS-related signals can
      be recorded. Two non-invasive bioelectronic measurements (skin resistance and
      potential) reflecting the activity of the ANS were performed at the skin surface.
      These measurements were complemented by thermovascular (skin microcirculation and
      skin temperature) and cardiorespiratory (instantaneous heart rate and
      instantaneous respiratory frequency) measurements. The bioelectric measurements
      were performed using noninvasive Ag/AgCl electrodes. Non-metallic NASICON (Na
      Super Ionic Conductor) electrodes were tested and compared with traditional
      electrodes for the optimization of bioelectric measurements. Signal analysis and
      data processing was accomplished by means of original indices on a specially
      designed PC-based software. The methodology was used to evaluate vigilance level,
      mental workload, and emotional response during tasks (sporting activity, mental
      calculation, olfactive stimuli) and in critical situations (car crash avoidance).

PMID- 7734123
TI  - Direct electron transfer bioelectronic interfaces: application to clinical
      analysis.
AB  - Bioelectronic interfaces based on direct electron transfer to proteins and
      enzymes immobilised at functional electrode surfaces are currently under
      development and the potential of two such systems for application to clinical
      measurement will be outlined. The first is the detection of free radical
      production via direct electrochemistry of cytochrome c immobilised covalently at
      modified gold electrodes. The redox protein cytochrome c has been immobilised
      covalently to gold electrodes surface-modified with N-acetyl cysteine via
      carbodiimide condensation. The electrodes thus produced were used to measure
      directly the enzymatic and cellular production of the superoxide anion radical
      (O2(-). The superoxide radical reduced the immobilised cytochrome c which was
      immediately re-oxidised by the surface-modified gold electrode poised at a
      potential of +25 mV (vs Ag/AgCl). The electron transfer rate constant (ket) of
      this process was 3.4 +/- 1.2 s(-1). The rate of current generation was directly
      proportional to the rate of O2(-) production. The essentially reagentless system
      produced was designed to be applied ultimately to continuous monitoring of free
      radical activity in vivo since there is evidence that oxygen-derived free radical
      species act as mediators which cause and perpetuate inflammation in disease
      states, including rheumatoid arthritis and neurodegenerative disorders. The
      second systems are pseudo-homogeneous immunoassays based on direct electron
      transfer to horseradish peroxidase. Horseradish peroxidase enzyme electrodes
      based on activated carbon (HRP-ACE) have been constructed by simple passive
      adsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734124
TI  - Synthesis of some new 1,3,4-oxadiazoline-2 thione derivatives with antibacterial
      activity.
AB  - Three new 5-[(1-benzoylamino)styren-1-yl]-1,3,4-oxadiazoline-2- thiones and nine
      of their Mannich bases with some primary and secondary amines and three N
      hydroxymethyl derivatives are synthesized. Some of the new derivatives were
      active against the bacteria Escherichia coli.

PMID- 7734125
TI  - Gas chromatographic determination of diisopyramide in the presence of some
      butyrophenones in human plasma.
AB  - A gas chromatographic procedure with flame ionization detection for the
      simultaneous determination of diisopyramide and butyrophenones in plasma was
      developed and evaluated. The quantitative analysis of diisopyramide and
      butyrophenones (BTPs) was performed in gas chromatograph equipped with packed
      column (glass column packed with 3% of phenylmethyl silicone-20% ph.), with
      previous Solid Phase Extraction (SPE) of drugs in C18 minicolumns. For all the
      drugs considered the accuracy of the proposed method has been evaluated through
      the recovery test which fell in the range 93-99%, once the absence of matrix
      interferences has been verified. The precision, expressed as coefficient of
      variation (CV%), has been of the order of 4%. A 15 m x 0.32 mm i.d. crosslinked,
      5% phenylmethyl silicone-coated fused-silica column was also quantitatively
      utilized and samples were injected using the on-column mode.

PMID- 7734126
TI  - Synthesis and pharmacological evaluation of 1,2,4-triazine and its congeners.
AB  - 3-[Mercapto]-n-propanoxy/methyl-ethanoxy branched chain in 5,6-Diphenyl- 1,2,4
      triazine were condensed with O-phenylene diamine or O- aminophenol or o
      aminothiophenol. The carboxylic groups of the synthesized compounds were cyclised
      to yield imidazoles, oxazoles and thiazoles. They were screened for their anti
      inflammatory response in albino rats against carrageenin induced paw oedema. The
      active compounds were also evaluated for their ED50 value in albino rats and
      analgesic activity in albino mice. The compounds exhibited significant anti
      inflammatory activity also showed marked protection against aconitine induced
      writhing response. The potent compounds showed high LD50 values.

PMID- 7734127
TI  - [Harvey or Cesalpino: who discovered blood circulation?].

PMID- 7734128
TI  - [100 years after his death: Jacopo Moleschott and his time (commemoration held at
      the Academy of Medicine in Turin on October 14, 1994)].

PMID- 7734129
TI  - The G.L. Brown Prize Lecture. Voltage-dependent calcium channels and their
      modulation by neurotransmitters and G proteins.

PMID- 7734130
TI  - Reflex respiratory responses to continuous and intermittent stimulation of
      afferent fibres from muscles in cats.
AB  - In anaesthetized cats, reflex respiratory responses were evoked by electrically
      stimulating proximal ends of cut nerves to gastrocnemius-soleus muscles of the
      left hindlimb. The direction of these responses, in the excitatory or inhibitory
      sense, depended on the types of afferent fibres stimulated and on the mode of
      stimulation. Continuous stimulation, delivered with stimuli of 0.1 ms at 200 or
      300 Hz, in all cases induced excitatory responses, consisting of increases in
      pulmonary ventilation, mainly caused by increases in tidal volume. Intermittent
      stimulation, which consisted of brief trains of stimuli repeated at 2-3 Hz,
      induced excitatory responses when afferent fibres with conduction velocities
      higher than 20 m/s were stimulated, while it induced inhibitory responses,
      consisting of decreases in pulmonary ventilation, tidal volume and respiratory
      frequency, when fibres with conduction velocities below 20 m/s were
      simultaneously stimulated with the high-conduction velocity fibres.

PMID- 7734131
TI  - The nature of increased blood-cerebrospinal fluid barrier exchange during CO2
      inhalation in newborn and adult rats.
AB  - Exposure of newborn (2-day-old) and adult rats to increasing levels of inspired
      carbon dioxide (5-15% CO2) resulted in increased steady-state cerebrospinal
      fluid/plasma ratios for a wide range of different-sized, lipid-insoluble
      permeability markers (molecular radius ranged from 0.43 nm for L-glucose to 5.3
      nm for immunoglobulin G). In control animals breathing room air and animals
      exposed to an elevated level of inspired CO2, steady-state CSF/plasma ratios for
      all permeability markers were proportional to their free diffusion coefficient.
      Steady-state CSF/plasma ratios in newborn animals were significantly higher than
      in adult animals, and at all ages the ratios for animals exposed to CO2 were
      higher than the ratios in control animals. In contrast to the increased steady
      state CSF/plasma ratios in animals exposed to elevated levels of inspired CO2,
      there was no significant difference in short-term (10 min after i.v. injection)
      CSF/plasma ratios for [14C]L-glucose between 10- to 20-day-old control rats and
      rats of similar age exposed to 10% inspired CO2. Steady-state experiments
      confirmed that CSF/plasma ratios for [14C]L-glucose in 20-day-old rats exposed to
      10% inspired CO2 were raised significantly (twice those measured in control
      animals breathing room air). The lack of effect of raised CO2 on short-term
      CSF/plasma ratios indicates that the significant increases in steady-state
      CSF/plasma ratios, in animals exposed to elevated levels of inspired CO2, are not
      due to a general increase in the permeability of the blood-CSF or blood-brain
      barriers; they are likely to be accounted for by CO2-induced reductions in the
      rate of CSF secretion.

PMID- 7734132
TI  - Effects of ductus arteriosus occlusion on pulmonary artery pressure during in
      utero ventilation in fetal sheep.
AB  - Seven fetal sheep were prepared to study the short-term effects of in utero
      ventilation and ductus arteriosus occlusion on pulmonary artery pressure and on
      fetal right ventricular function assessed using the right atrial pressure-right
      ventricular stroke volume relationship. Nine days post-surgery (140 days
      gestation), blood gas and haemodynamic values were obtained before and during in
      utero ventilation with 100% O2, and during ventilation with the ductus arteriosus
      occluded. Oxygen content increased significantly from 7.2 to 14.5 ml dl-1 with
      ventilation and remained elevated at 14.4 ml dl-1 with ventilation with the
      ductus arteriosus occluded. In utero ventilation produced a left to right atrial
      pressure gradient and depression of the right atrial pressure-right ventricular
      stroke volume relationship. Ductus arteriosus occlusion during in utero
      ventilation reduced the left to right atrial pressure gradient, and along with a
      decrease in pulmonary artery pressure, resulted in an upward shift of the right
      atrial pressure-right ventricular stroke volume relationship, but only to the
      preventilation level. This study indicates that the fetal right atrial pressure
      right ventricular stroke volume relationship is significantly altered, both by
      changes in the left to right atrial pressure gradient and by changes in pulmonary
      artery pressure seen with in utero ventilation and subsequent ductus arteriosus
      occlusion.

PMID- 7734133
TI  - Effect of central adenosine on brainstem blood flow in fetal sheep.
AB  - The effect of the adenosine analogue R-N6-(phenylisopropyl)adenosine (R-PIA) on
      blood flow to the medulla and pons was examined in unanaesthetized fetal sheep.
      Microspheres labelled with isotopes were used to determine blood flow before and
      after instillation of 0.2 or 0.5 microgram R-PIA into the cerebrospinal fluid of
      the fourth ventricle. Blood flow to the medulla, which had a mean value (+/-
      S.E.M.) of 285 +/- 41 ml min-1 (100 g)-1 during the control period, was not
      changed by the central instillation of R-PIA. Blood flow to the pons was also not
      affected. These data indicate that central adenosine, which depresses respiratory
      drive in fetal sheep, acts by mechanisms independent of removal of carbon dioxide
      from the brainstem.

PMID- 7734134
TI  - Vaginal birth versus elective caesarean section: effects on gastric function in
      the neonate.
AB  - Plasma gastrin concentration increases in late gestation and reaches a peak at
      birth or shortly after birth in many species ('neonatal hypergastrinaemia'). We
      investigated the hypothesis that gastrin and gastric acid secretion in the
      neonate is influenced by the final rise in plasma cortisol associated with
      spontaneous (vaginal) birth. Caesarean-delivered (CD, n = 28) or vaginally
      delivered (VD, n = 24) premature or full-term piglets (97-115 days gestation)
      were killed immediately after birth (using pentobarbitone). Compared with newborn
      CD pigs, the newborn VD pigs had significantly higher (P < 0.05) concentrations
      of cortisol (669 +/- 60 versus 223 +/- 2 nM) and gastrin (57 +/- 4 versus 33 +/-
      1 pM) in plasma, and significantly lower gastric fluid pH (3.3 +/- 0.2 versus 4.7
      +/- 0.3), amidated (bioactive) gastrin in the antrum (550 +/- 77 versus 1220 +/-
      29 pmol g-1) and glycine-extended (precursor) gastrin in the antrum (81 +/- 10
      versus 143 +/- 5 pmol g-1). There were significant linear correlations between
      log plasma cortisol values and plasma gastrin (r = 0.40, P < 0.05) or gastric
      fluid pH (r = -0.51, P < 0.05) in newborn pigs. The effects of cortisol in the
      immediate postnatal period were investigated in forty-one CD pigs born at 111-112
      days gestation and treated with saline, metyrapone (an inhibitor of cortisol
      synthesis) or adrenocorticotrophic hormone (ACTH) from 0 to 7 days after birth.
      At 7 days, plasma gastrin in ACTH-treated pigs (elevated plasma cortisol) was
      significantly lower than in saline-treated pigs, but not different from that in
      metyrapone-treated pigs (low plasma cortisol). No treatment effects were observed
      postnatally for antral gastrin and fundic cobalamin-binding protein
      concentrations. These results suggest that in the intrapartum period the high
      circulating cortisol levels stimulate the normal rise in gastrin and acid
      secretion associated with spontaneous vaginal delivery in the piglet, whereas
      postnatally, cortisol is unlikely to play an important role in the subsequent
      development of gastrin and acid secretion.

PMID- 7734135
TI  - Control of gastric emptying in the pig: influence of cholecystokinin,
      somatostatin and prokinetic agents.
AB  - The influence of systemic arterial infusions of cholecystokinin octapeptide
      (CCK8) and somatostatin, and injections of cisapride, metoclopramide and atropine
      on gastric emptying were studied in eight pigs. Gastric emptying of dry matter
      (DM) and liquids (Cr-EDTA as marker) was measured, in pigs fitted with a gastric
      cannula, by evacuation of gastric contents either immediately after the pigs had
      finished feeding, or 3 h after being fed a meal containing 1200 g of a finely
      ground barley diet mixed with 2.41 water. Gastric emptying of DM and liquids
      during the feeding period was not significantly altered by cisapride (0.15 and
      0.3 mg kg-1-1), metoclopramide (0.2 mg kg-1), CCK8 (250 ng kg-1 h-1) or
      somatostatin (1.8 and 4.5 micrograms kg-1 h-1); atropine (0.06 mg kg-1) slowed
      emptying of DM (by 53 +/- 6%; P < 0.001) and of liquids (by 51 +/- 7%, P < 0.01).
      In contrast, the amount of DM emptied within 3 h of feeding was significantly
      reduced with CCK8 (250 ng kg-1 h-1; by 14 +/- 3%, P < 0.001) and with
      somatostatin (1.8 microgram kg-1 h-1; by 10 +/- 4%; P < 0.001). There was no
      increase in emptying of DM or liquids with cisapride or metoclopramide; indeed,
      there was actually a reduction in liquid emptying (by 13 +/- 6%; P < 0.05) with
      cisapride (0.3 mg kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734136
TI  - Glibenclamide, a blocker of ATP-sensitive potassium channels, reverses endotoxin
      induced hypotension in pig.
AB  - In anaesthetized, mechanically ventilated, indomethacin-treated pigs, we infused
      E. coli endotoxin (LPS, 20 micrograms kg-1 h-1, i.v.). After 150 min of
      endotoxaemia, 10 mg kg-1 glibenclamide (an ATP-sensitive K+ channel antagonist)
      was administered i.v. over 5 min. Vascular variables were recorded before
      (control), after 150 min of endotoxaemia and 5, 15 and 30 min after glibenclamide
      infusion. Glibenclamide transiently (within 5 min) increased systemic arterial
      pressure, reduced by LPS administration, without an effect on cardiac output. Our
      data indicate that ATP-sensitive K+ channels may play a partial role in the
      vascular changes due to endotoxaemia.

PMID- 7734137
TI  - Properties of an identified dopamine-containing neurone in culture from the snail
      Helisoma.
AB  - The giant neurone in the left pedal ganglion of the snail Helisoma trivolvis is
      homologous with the giant dopaminergic neurone of Planorbis corneus, because the
      neurones have a very similar location and morphology, and react similarly with
      glyoxylic acid to produce an intense blue fluorescence, indicating the presence
      of dopamine. Each of these neurones is therefore referred to as a giant
      dopaminergic neurone, or GDN. Conditions for the extension of neurites and
      formation of chemical junctions in culture have been determined for the H.
      trivolvis GDN, and compared with other neurones from this species. The pattern of
      neurites that extended from the neurone was indistinguishable from that of
      another identified aminergic neurone, the large serotonergic neurone (LSN), but
      differed markedly from many other central neurones. However, the type of
      substrate also greatly affected the pattern of the neurites observed. Some of the
      electrical properties of the GDN in culture differed from those recorded in situ:
      peak spike amplitude was increased, spike half-width reduced and the firing
      pattern of the neurone was altered. However, the resting membrane potential was
      very similar. The GDN formed chemical and electrical junctions in culture. The
      chemical junctions formed were of the same type as those found in situ. They
      formed rapidly, within 18 h after plating, but were not stable and were lost
      within 48 h, to be replaced by a non-rectifying electrical junction. A chemical
      junction may form in either direction between the GDN and the LSN, but only
      rarely did such junctions allow transmission in both directions, as observed in
      situ. Experiments in which neurones were plated out at different times suggested
      that the direction of formation of the chemical junction was not dependent on the
      degree or state of neurite extension.

PMID- 7734138
TI  - The effect of experimental hypertension on retinal vascular autoregulation in
      humans: a mechanism for the progression of diabetic retinopathy.
AB  - Since the retinal vessels have no sympathetic innervation, blood flow in response
      to raised blood pressure is dependent on autoregulation. To determine the effect
      of hypertension on retinal haemodynamics and the autoregulatory capacity of the
      retinal circulation under conditions of normoglycaemia and hyperglycaemia,
      retinal blood flow was measured before and after raising the systemic blood
      pressure in ten normal control subjects, ten diabetic subjects with blood glucose
      < 10 mmol l-1 and ten diabetic subjects with blood glucose > 15 mmol l-1. A
      controlled rise in systemic blood pressure was achieved using an intravenous
      infusion of tyramine. Retinal volume flow was determined from red cell velocity
      using laser Doppler velocimetry and from retinal vessel diameter measurements
      using digital image analysis of fundus photographs. With a 40% increase in mean
      arterial blood pressure (MAP), there was a significant increase in retinal blood
      flow of 32.9 +/- 7.1% in non-diabetic controls. In diabetics at the low blood
      glucose level, the increase in retinal blood flow was significant at 30% increase
      in MAP (23.6 +/- 8.7%, P = 0.032) and at 40% increase (49.9 +/- 12.03%, P =
      0.004). Diabetics with high blood glucose failed to autoregulate at any of the
      increased levels of MAP (15% increase, 27.0 +/- 11.1%; 30% increase, 66.9 +/-
      19.8%; and 40% increase, 101.9 +/- 21.4%; P < 0.022). The coefficients of
      autoregulation showed that in non-diabetic controls, retinal vascular
      autoregulation broke down with increases in MAP of between 30 and 40%. In
      diabetic subjects, it broke down between 15 and 30% in normoglycaemia and at less
      than 15% in hyperglycaemia. This study demonstrates an impairment in retinal
      vascular autoregulation in response to raised systemic blood pressure in diabetic
      subjects, more so at an elevated blood glucose level, thus providing a mechanism
      for the detrimental effect of hypertension on diabetic retinopathy.

PMID- 7734139
TI  - Contribution of extracellular calcium to intracellular pH-induced changes in
      spontaneous force of rat portal vein.
AB  - Normal spontaneous mechanical activity of isolated rat portal vein is critically
      dependent on external calcium as a source of contractile activation and this
      force is modified by alteration of intracellular pH. We have studied the
      involvement of the extracellular calcium pool in intracellular pH-induced changes
      in force. Intracellular pH was changed, at constant external pH, by NH4Cl
      application and withdrawal in bathing [CaCl2] varying between 3 and 0 mM, and
      manoeuvres were performed in the presence and absence of either the intracellular
      calcium mobilizer caffeine or the calcium channel blocker nifedipine. The results
      indicate that alteration of spontaneous force with intracellular pH has an
      absolute requirement for calcium entry from outside and calcium release from
      caffeine-sensitive intracellular stores.

PMID- 7734140
TI  - The mechanism of relaxation in response to magnesium by the aorta of pregnant
      rats with salt-induced hypertension.
AB  - The study examined the effect of salt-induced hypertension on vascular relaxation
      in response to magnesium sulphate during pregnancy. Pregnant Wistar rats were fed
      for 6 weeks on a diet containing 0.3% (control) and 8.0% (test) sodium chloride.
      Aortic rings were then removed and contracted with 10(-7) M phenylephrine or 30
      mM potassium chloride. High salt intake increased the systolic blood pressure of
      the rats and increased the relaxation of phenylephrine-contracted intact rings in
      response to magnesium sulphate. Neither endothelium removal nor treatment with
      10(-6) M indomethacin altered the relaxation of rings from the two groups of
      rats, when contracted with potassium chloride. Both processes significantly (P <
      0.05) and similarly decreased the sensitivity and the maximal relaxation of rings
      from test rats contracted with phenylephrine; the relaxation of rings from the
      control rats was not altered. The results suggest that the relaxation of isolated
      rat aortic rings contracted with phenylephrine is enhanced in pregnant rats with
      salt-induced hypertension. The mechanism involved in this enhancement is
      dependent on the vascular endothelium and receptor activation, and is
      indomethacin sensitive.

PMID- 7734141
TI  - Skeletal muscle buffer value, fibre type distribution and high intensity exercise
      performance in man.
AB  - Interrelationships between quadriceps femoris muscle buffer value (beta), fibre
      type distribution, and lactate concentration and pH following short-term high
      intensity exercise were examined in eighteen young healthy human volunteers.
      Muscle biopsy samples were taken from the lateral portion of the quadriceps
      femoris muscle at rest and after fatiguing dynamic or isometric exercise.
      Isometric exercise required the maintenance of 60% quadriceps maximum voluntary
      contraction, and dynamic exercise, the performance of a modified Wingate Test.
      The muscle buffer value displayed a positive, but non-significant correlation
      with the relative area of the muscle occupied by type II fibres (r = 0.42, P =
      0.09). An elevated beta was associated with a lesser decrement in muscle pH
      during intensive exercise but did not permit the accumulation of a higher muscle
      lactate concentration or allow for an enhanced dynamic or isometric exercise
      performance. A superior performance during dynamic exercise was associated with a
      high concentration of muscle lactate and a low muscle pH post-exercise; in turn,
      each of these factors was positively dependent on the relative area of the muscle
      occupied by type II fibres. The converse was found for isometric exercise, where
      there was a tendency for an enhanced performance to be associated with a low
      muscle lactate and high muscle pH post-exercise. No significant relationship
      between the relative type II fibre area and isometric performance capacity could
      be established. It was concluded that the muscle buffer value is not a major
      limiting factor to the performance of high intensity exercise, suggesting that
      the involvement of intramuscular acidosis in the development of fatigue may be
      indirect. The most important determinant of high intensity exercise capacity
      appears to be the proportional area of the muscle occupied by type II fibres,
      where a high value provides for a superior dynamic but inferior isometric
      exercise performance.

PMID- 7734142
TI  - Involvement of basic fibroblast growth factor NH2 terminus in nuclear
      accumulation.
AB  - The human basic Fibroblast Growth Factor (bFGF) gene was shown to encode four
      polypeptides by an alternative use of initiation codons (three CUG and one AUG).
      In this report, we present a comparative study of the fate and intracellular
      localization of individual bFGF isoforms. For this purpose, we have produced the
      various bFGF isoforms in E. coli and purified them to homogeneity: the 210 amino
      acid form initiated at CUG1 that contains a nuclear localization sequence (NLS),
      the 155 amino acid form (AUG-mediated initiation) and the 146 amino acid form
      (processed form extracted from tissues). While the different bFGFs were taken up
      by the cell with equal efficiency, more of the 210 amino acid form accumulated in
      the nucleus and represented 36% of the internalized bFGF compared with 15% in the
      others. A chimeric protein containing the minimal SV40 Large T NLS (SV40NLS)
      fused to the 155 amino acid bFGF form (SVbFGF) behaves like the native 155 amino
      acid form, indicating that nuclear accumulation of exogenous bFGF is not mediated
      by the NLS-associated function. These results suggest that the amino-terminal
      part of the 210 amino acid bFGF contains a sequence responsible for its nuclear
      retention. Bioactivities of the different forms were tested on adult bovine
      aortic endothelial (ABAE) cells. The bFGF degradation pathways, mitogenic
      activity and stimulation of rRNA synthesis appeared to be the same for all bFGFs
      but the stimulation of plasminogen activator was enhanced by the 210 amino acid
      form and correlated with nuclear accumulation.

PMID- 7734143
TI  - The immunolocalization of basic fibroblast growth factor in the mouse uterus
      during the initial stages of embryo implantation.
AB  - Mammalian embryo implantation involves a series of complex interactions between
      maternal and embryonic cells. Uterine polypeptide growth factors may play
      critical roles in these cell interactions. Basic fibroblast growth factor (basic
      FGF) is a member of a family of growth factors. This growth factor may be
      potentially important for the process of embryo implantation because it (a) is
      stored within the extracellular matrix and is thus easily available during embryo
      invasion, (b) is a potent modulator of cell proliferation and differentiation and
      (c) stimulates angiogenesis. The immunolocalization of basic FGF in the uterus
      during the peri-implantation period of pregnancy is presented in this study.
      Uterine tissue samples were obtained on days 6-9 of pregnancy with day 1 of
      pregnancy being the day of a vaginal copulatory plug. Uterine samples were fixed
      in Bouin's fluid for no longer than 18 h. Following fixation and paraffin
      embedding, sections were exposed to primary antisera made in rabbits against
      either (a) human recombinant basic FGF or (b) 1-24 synthetic fragment of bovine
      basic FGF. The primary antibody was followed by biotinylated goat anti-rabbit IgG
      and a biotin-avidin-peroxidase complex. There were no differences in the
      immunolocalization of basic FGF using either source of primary antibody. Our
      results demonstrated both temporal and spatial changes in the localization of
      immunoreactive basic FGF within the implantation chamber during days 6-9 of
      pregnancy. Inter-implantation sites resembled the non-pregnant uterus with basic
      FGF present in extracellular matrices including basal laminae. On day 6 of
      pregnancy, decidual cells within the primary decidual zone lacked both
      intracellular and pericellular basic FGF while non-decidualized uterine stroma
      resembled inter-implantation sites. By days 7-8 of pregnancy, the secondary
      decidual zone had formed and was characterized by the distinct pericellular
      localization of basic FGF around individual decidual cells. By day 9 of
      pregnancy, the mesometrial region was forming and contained cords of decidual
      cells and a labyrinth of maternal blood vessels. The decidual cells contained
      diffuse intracellular basic FGF. Trophoblast cells were devoid of basic FGF at
      all times examined. These results indicate that basic FGF is present within the
      implantation chamber on days 6-9 of pregnancy and may be involved in the decidual
      cell response, trophoblast cell invasion and angiogenesis.

PMID- 7734144
TI  - VEGF receptor subtypes KDR and FLT1 show different sensitivities to heparin and
      placenta growth factor.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic growth factor which
      binds to two structurally related tyrosine kinase receptors denoted KDR and FLT1.
      To compare the interaction of VEGF with each receptor, cell lines which express
      individual receptor subtypes were identified using Northern blot hybridization.
      Bovine aortic endothelial (ABAE) cells and WM35 melanoma cells were found to
      express KDR, while FLT1 was primarily expressed on SK-MEL-37. Both receptor
      subtypes were detected on another melanoma cell line (WM9). Heparin augmented
      VEGF binding to KDR-expressing cells (ABAE and WM35), but inhibited VEGF binding
      to FLT1-expressing cells (SK-MEL-37 and WM9). The concentration of heparin
      required for half maximal stimulation of VEGF binding to KDR-expressing cells
      (500 ng/ml) was 25 times greater than that required for half maximal inhibition
      of binding to FLT1-expressing cells (20 ng/ml). In WM9 cells, the effect of
      heparin was bimodal; low concentration inhibited, while higher concentrations
      stimulated binding of 125I-VEGF. Placenta growth factor (PIGF-1) is a recently
      described growth factor structurally similar to VEGF. PIGF-1 had a negligible or
      no effect on 125I-VEGF binding to KDR-expressing cells (ABAE, WM35), but did
      complete for binding to FLT1-expressing cells (SK-MEL-37 and WM9). Addition of
      heparin had no effect on its ability to compete for binding with 125I-VEGF. The
      data indicate differential regulation of the two VEGF receptors by heparin and
      extended specificity of FLT1 receptor, but not KDR, for binding PIGF-1 growth
      factor.

PMID- 7734145
TI  - Transforming growth factor-beta 1 enhances serum-induced dephosphorylation of the
      P53 protein in cell lines growth-inhibited by this factor.
AB  - A 24 hr TGF-beta 1 treatment (4 ng/ml) of SV40-transformed WI38 embryonic
      fibroblasts (VA13 cells) causes a moderate but reproducible inhibition of their
      serum-stimulated growth. By immunoprecipitation with the PAb122 antibody, we show
      that serum stimulation of previously serum-deprived cells causes a
      dephosphorylation of the wild type P53 protein, which is accentuated by the TGF
      beta 1 treatment. The TGF-beta 1-enhanced dephosphorylation effect is also
      observed in two other cell lines growth-inhibited by TGF-beta 1, but which do not
      contain Large T (mink lung CCL64 and human KHOS cells). On the contrary, TGF-beta
      1 treatment of the untransformed WI38 fibroblasts stimulates their growth,
      without affecting the phosphorylation of P53. Such treatment did not affect the
      expression of the corresponding mRNA nor the level of synthesis of the protein.
      The results suggest that the P53 protein could be a downstream target of TGF-beta
      1 action on those cells growth-inhibited by the factor.

PMID- 7734146
TI  - Transforming growth factor beta (TGF-beta) and dexamethasone have direct opposing
      effects on collagen metabolism in low passage human dermal fibroblasts in vitro.
AB  - Collagen metabolism is a balance between synthesis and lysis. Both are under
      tight regulatory control. TGF-beta reverse the impairment of healing seen after
      glucocorticoid treatment in vivo. Both TGF-beta and glucocorticoids are known to
      regulate collagen metabolism directly. We have examined the effect of
      dexamethasone and of TGF-beta individually and in combination on the regulation
      of procollagen type 1, interstitial collagenase and tissue inhibitor of metallo
      proteinase-1 (TIMP-1) synthesis at both the protein and mRNA levels in low
      passage human dermal fibroblasts. Dexamethasone treatment decrease synthesis of
      procollagen and caused a dose dependent down-regulation of TIMP-1 synthesis.
      Interstitial collagenase synthesis by fibroblasts was detectable but low. Thus,
      glucocorticoid treatment of fibroblasts tilts the balance of collagen metabolism
      away from accumulation. TGF-beta had opposing effects, stimulating both
      procollagen and TIMP-1 synthesis at the protein and mRNA levels. TGF-beta was
      able to cause a dose-dependent reversal of the glucocorticoid induced decrease in
      procollagen and TIMP-1 synthesis. Stimulation of healing in glucocorticoid
      treated animals by TGF-beta may be by the direct action of this agent upon
      fibroblast collagen metabolism.

PMID- 7734147
TI  - Osteogenic protein-1 (OP-1) expression and processing in Chinese hamster ovary
      cells: isolation of a soluble complex containing the mature and pro-domains of OP
      1.
AB  - We have characterized the expression and processing of Osteogenic Protein-1 (hOP
      1), a bone morphogenic protein of the TGF-beta family, in Chinese hamster ovary
      cells. The hOP-1 is initially synthesized as a monomeric 50 kDa pro-protein that
      is dimerized, glycosylated, and then proteolytically cleaved at the Arg-Xaa-Xaa
      Arg maturation site in an acidic cellular compartment before secretion into the
      medium. Of the four potential N-linked glycosylation sites two are used, one in
      the mature domain and one in the pro-domain. Gel permeation chromatography of
      secreted hOP-1 in physiological buffers yields an apparent molecular weight of
      110-120 k, indicating that after proteolytic processing the two pro-domains
      remain non-covalently associated with the disulfide linked mature dimer in a
      complex termed soluble hOP-1. Purified soluble hOP-1 is significantly more
      soluble in physiological buffers than the purified mature OP-1.

PMID- 7734148
TI  - Osteogenic protein-1 (BMP-7) inhibits cell proliferation and stimulates the
      expression of markers characteristic of osteoblast phenotype in rat osteosarcoma
      (17/2.8) cells.
AB  - We recently showed that osteogenic protein-1(OP-1), a bone morphogenetic protein
      member of TGF-beta superfamily, induces endochondral bone formation in vivo, and
      stimulates growth and differentiation of osteoblasts in rat calvarial-derived
      cell cultures. In the present study, we examined the effect of OP-1 on cell
      growth and expression of markers that are characteristic of osteoblast phenotype
      using the clonal rat osteosarcoma cells (ROS 17/2.8). A comparison of OP-1 and
      TGF-beta 1 effects on cell growth showed that, both OP-1 and TGF-beta 1 inhibited
      DNA synthesis up to 90 percent and 60 percent of the controls at concentrations
      of 10 ng/ml and 1 ng/ml, respectively, in serum-free medium. In the presence of
      5% serum, TGF-beta 1 did not have any significant inhibitory effects while 40 ng
      OP-1/ml inhibited the DNA synthesis up to 80% of the controls. Examination of
      collagen synthesis showed that 40 ng OP-1/ml increased the expression of type I
      collagen mRNA, and thus increased collagen synthesis (4-fold), as examined by
      collagenase-digestible protein. Evaluation of markers that are characteristic of
      the osteoblast phenotype demonstrated that OP-1 stimulated cAMP production in
      response to PTH (10-fold at 200 ng/ml), alkaline phosphatase specific activity
      (ALPase) (4-fold at 80 ng/ml), and osteocalcin (OC) synthesis (4.5-fold at 40
      ng/ml). Northern blot analysis revealed that OP-1 increased mRNA expression for
      both ALPase and OC in a dose-dependent manner. These data collectively
      demonstrate that OP-1 suppresses cell proliferation and stimulates the expression
      of markers characteristic of osteoblast phenotype in rat clonal osteoblastic
      osteosarcoma cells (ROS 17/2.8).

PMID- 7734149
TI  - Computer modelling of kappa carrageenan-mannan interactions.
AB  - Molecular modelling has been used as a theoretical approach to investigate the
      kappa carrageenan structure and its interactions with mannan chains. Calculations
      revealed the existence of six minima for the kappa carrageenan structure in
      solution. Two of them were very close to the structure found in the solid state.
      The methodology allowed the calculation of a theoretical counterpart of the
      structures based on x-ray fibre diffraction studies. In the second step of this
      study, we have shown that there is the possibility of interactions between kappa
      carrageenan double helices and mannan chains. This interacting process is allowed
      by the flexibility of the mannan chains and structural changes of the kappa
      carrageenan double helices. The calculations suggest that a disaccharide mannan
      fragment might be required for recognition. The results of our investigation are
      in good agreement with a model of gel structure based on experimental data. This
      approach could be applied to simulate and predict other associations in molecular
      assemblies.

PMID- 7734150
TI  - Receptor interactions of the position 4 side chains of angiotensin II analogues:
      importance of aromatic ring quadrupole.
AB  - A triad of interacting groups (TyrOH-His-O2C) in angiotensin II (ANG II) has been
      postulated to create the tyrosinate anion pharmacophore (tyanophore) responsible
      for receptor activation/triggering (Biochim. Biophys. Acta 1991, 1065, 21). In
      the present study we investigated the effects on bioactivity of substituting the
      Tyr4 residue in [Sar1]ANG II with other anionic or electronegative amino acids,
      and with a number of aromatic amino acids lacking a hydroxyl group. [Sar1
      Nva(delta-OH)4]ANG II, [Sar1 Nva(delta-OCH3)4]ANG II, [Sar1 Met4]ANG II, [Sar1
      Gln4]ANG II, [Sar1 Glu4]ANG II and [Sar1 DL-Alg]ANG II had agonist activities in
      the rat isolated uterus assay of 4, 3, 19, 10, < 0.1 and < 0.1%, respectively, of
      that of ANG II. [Sar1 Nal4]ANG II, [Sar1 Pal4]ANG II, [Sar1 DL-Phg(4'-F)4]ANG II,
      [Sar1 Phe(4'-F)4]ANG II, [Sar1 Phe(F5)4]ANG II and [Sar1 His4]ANG II had agonist
      activities of 4.5, 7, < 0.1, 0.2, 1 and 0.6%, respectively. All peptides
      investigated were devoid of measurable antagonist activity except [Sar1 Phe(4'
      F)4ANG II (pA2 = 7.7). These findings illustrate that anionic or electronegative
      aliphatic side chains replacing tyrosinate at position 4 can partially activate
      the angiotensin receptor. For ANG II analogues containing an aromatic amino acid
      other than Tyr at position 4, ligand binding and agonist activity are not
      dependent on the electronegativity or dipole moment of the aromatic ring, or on
      the ability of the 4' ring substituent to accept a proton.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7734151
TI  - Specificity in the recognition of crystals by antibodies.
AB  - We show that IgG molecules isolated from the serum of rabbits injected with
      crystals of monosodium urate monohydrate, magnesium urate octahydrate and
      allopurinol, can each catalyze the nucleation of the same type of crystal to
      which they were exposed. These results generalize previous findings related to
      monosodium urate monohydrate and assess the idea that the invasion of a foreign
      crystal into an organism may amplify a population of antibodies which bear in
      their binding sites an imprint of the crystal surface structure. Such antibodies
      can further act as nucleating templates which accelerate crystal formation in
      vitro. Antibodies isolated from rabbits injected with sodium urate crystals do
      not cross-react or cross-react only to a low extent with antibodies isolated from
      rabbits injected with crystals of either magnesium urate or allopurinol. These
      results indicate a high specificity of the elicited antibodies, as these can
      distinguish between nuclei of crystals having similar molecular and structural
      characteristics.

PMID- 7734152
TI  - Binding of malate dehydrogenase and NADH channelling to complex I.
AB  - As previously reported, mitochondrial malate dehydrogenase (MDH) binds to
      purified complex I of the electron transport system. With conditions used in
      previous reports, MDH binds even more extensively, but probably predominantly non
      specifically, to the matrix side of the inner mitochondrial membrane of
      submitochondrial particles (SMP). Herein we report experimental conditions for
      highly specific binding of malate dehydrogenase to complex I within SMP. These
      conditions permit us to demonstrate NADH channelling from malate dehydrogenase to
      complex I using the competing reaction test. This test, though not ideal for all
      situations, has several advantages over the enzyme buffering test previously
      used. These advantages should facilitate further studies elucidating NADH
      channelling to complex I from MDH and other dehydrogenases. Independent evidence
      of NADH channelling to the electron transport chain and the potential advantages
      of substrate channelling in general are also discussed. Substrate channelling
      from MDH in particular may be especially beneficial because of the unfavourable
      equilibrium and kinetics of this enzyme reaction.

PMID- 7734153
TI  - Immunoglobulin-like domain is present in the extracellular part of the receptor
      tyrosine kinase from the marine sponge Geodia cydonium.
AB  - We have isolated and characterized two cDNAs from the marine sponge Geodia
      cydonium coding for a new member of a receptor tyrosine kinase of class II. The
      deduced amino acid sequence shows two characteristic domains: (i) the tyrosine
      kinase domain; and (ii) an immunoglobulin-like domain. The latter part shows high
      homology to the vertebrate C2 type immunoglobulin domain. This result
      demonstrates that immunoglobulin domains are not recent achievements of higher
      animals but exist also in those animals which have diverged from other organisms
      about 800 million years ago.

PMID- 7734154
TI  - Separate regulation of a membrane protein, gp130, present in receptor complex
      specific for interleukin-6 and other functionally related cytokines.
AB  - In addition to specific ligand binding elements, receptor assembly for
      interleukin(IL)-6, oncostatin-M, leukaemia inhibitory factor, ciliary
      neurotrophic factor and IL-11 includes an additional unit, gp130. This molecule
      is a transmembrane glycoprotein of 130 kDa. In this paper, reviewing molecular,
      biochemical and functional data on gp130, we describe the dissimilar action of IL
      3 on the expression of the binding unit of the IL-6 receptor and that of gp130.
      According to FACS studies, resting basophils express only IL-6 receptors and no
      gp130 molecules on the plasma membranes. After incubation with IL-3, the surface
      appearance and de novo transcription of gp130 was shown by FACS and mRNA
      polymerase chain reaction analysis.

PMID- 7734155
TI  - [Distortion product otoacoustic emissions in Meniere's disease].
AB  - We present the results of the distortion product otoacustic emission testing
      performed in 24 patients diagnosed of Meniere's disease. Significant differences
      in the evoked response of both normal and pathologic ears, and a correlation
      between lesion degree and auditive impairment, were found. On the other hand,
      response of the normal ears was lower than in a same age, normal-hearing subjects
      group.

PMID- 7734156
TI  - [Study of 288 stapedectomies performed between 1986 and 1991].
AB  - A review of 288 stapedectomies performed between 1986 and 1991 was carried out.
      Pre- and post-surgical (within six to nine months) audiometries were studied,
      analyzing the 250 Hz, 500 Hz, 1,000 Hz, 2,000 Hz and 4,000 Hz frequencies. No
      significant differences between age and sex, type of prosthesis or final auditive
      gain were found. Patients were distributed in six groups according to their
      initial audiometry, achieving higher auditive gain those with and worse initial
      audition.

PMID- 7734157
TI  - [Efficacy of topical ciprofloxacin in the treatment of chronic otorrhea].
AB  - The aim of the present study was to assess the clinical and bacteriological
      efficacy of ciprofloxacin in the treatment of chronic otitis media. Ciprofloxacin
      was randomly administered for ten days to two groups of patients. Group A was
      given 500 mg. orally twice a day. Group B received drops of ciprofloxacin in
      saline solution locally twice a day. We obtained a favorable clinical and
      bacteriological response. Bacteriological response observed in group B was
      statistically higher than that of group A (p < 0.01). Results obtained in this
      study suggest that ciprofloxacin locally administered is very effective in the
      treatment of chronic otitis media.

PMID- 7734158
TI  - [Determination of the diagnostic efficacy of the multi-RAST test (Phadiotop) in
      allergic rhinitis].
AB  - Diagnosis of IgE mediated allergic rhinitis is based on medical history. Prick
      test (of the skin) and determination of increased IgE levels by serum (PRIST and
      RAST) as well as intranasal provocation test. To search the potential diagnostic
      value of a multi-RAST test (Phadiotop) in serum and nasal fluids, 508 with
      rhinitis were studied: In 267 patients nasal allergy was confirmed by the above
      mentioned tests. Phadiotop revealed a sensitivity of 98.1% in serum and 79.0% in
      nasal fluid. Specificity of Phadiotop was 95.9% in serum and 97.5% in nasal
      fluid. Our results show that the determination of Phadiotop can be considered as
      a very sensitive screening test for allergy detection.

PMID- 7734159
TI  - [Pansinusitis: approach to its etiopathogenesis].
AB  - Local factors and external conditions are determinants for pansinusitis. We
      present 10 cases in which 20% are of unknown origin, 30% have allergic
      antecedents, 20% show hypersensitivity to aspirin, 20% have an immotile-cilia
      syndrome and 10% are caused by exogenous factors. Surgical treatment is performed
      in 70% of the cases, always followed by a long-term medical therapy. Forty per
      cent of the cases show a chronic progress despite the type of treatment applied.

PMID- 7734160
TI  - [The middle turbinate as the cause of sinusal pathology].
AB  - The middle turbinate and its anatomical variations (concha bullosa and
      paradoxically bent middle turbinate) may be the site of different pathologies due
      to the alteration of the sinus function at the key area of the osteomeatal
      complex. In the present work we study 4 cases of concha bullosa and 4 cases of
      paradoxically bent middle turbinates, associated to recurrent sinusitis and/or
      headaches, which underwent endoscopic surgery. Improvement was achieved in all
      recurrent circumscribed sinusitis. One of the patients with bilateral
      paradoxically bent middle turbinate had an associated pansinusitis, and he only
      improved in his right side. An aspergilloma was found inside one of the conchae
      bullosae. Headaches improved in all the cases analyzed. Anatomic variations may
      be the cause of recurrent sinusal pathology or isolated headaches and it should
      be noted that, in correctly selected groups, a dramatic improvement can be
      achieved with a minor surgical procedure on the middle turbinate or ethmoidal
      infundibulum.

PMID- 7734161
TI  - [Nasal endoscopic surgery in complicated ethmoiditis].
AB  - Spread of infection from paranasal sinuses is uncommon but, when it occurs may
      lead to serious ocular or intracranial complications. In this article we present
      four patients, three of them with orbital complications and one with an
      intracranial abscess, who were successfully treated with endoscopic surgery of
      the sinuses and antibiotic therapy. We describe some potential advantages of this
      approach.

PMID- 7734162
TI  - [Microbiological study of the nasopharynx].
AB  - A microbiological study of the posterior wall of the nasopharynx have been
      carried out in 90 children subjected to adenoidectomy by chronically
      hypertrophied and infected adenoids. Streptococcus pneumoniae, Haemophilus
      influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Staphylococcus
      aureus are the most important pathogens responsible for upper respiratory tract
      infection. Adenoidectomy produces a physiological effect on the nasopharyngeal
      microflora by converting an abnormal flora into a nearly normal one. It has been
      found out that there is a relation between nasopharyngeal pathogens and the
      seasonal periods, showing a decrease in summer.

PMID- 7734163
TI  - [Prophylactic antibiotic therapy with amoxicillin-clavulanic acid in
      oropharyngeal surgery].
AB  - The present paper shows the results of a randomized, prospective trial carried
      out on 170 patients undergoing elective surgery for oropharyngeal cancer. These
      patients were distributed in two groups that received a prophylactic therapy with
      amoxicillin and clavulanic acid, for 24 hours and 5 days, respectively. Comparing
      results of short-term and long-term prophylaxis. Among patients undergoing only
      total or partial laryngectomies, no differences between both groups were found.
      Among patients who already had a tracheostomy, the rate of local infection was
      higher in the short-time group. Duration of prophylaxis in high-risk surgery,
      such as that requiring flap reconstruction, needs further investigation.

PMID- 7734164
TI  - [S/z ratio in glottic closure defects].
AB  - The quotient between the maximum phonation time (MPT) of the sound /s/ and a
      vowel sound, measures the relation of resistances to the expiratory air flow.
      When the sound /s/ is emitted, resistance is located at the teeth, and when a
      vowel is phonated, the site of resistance is the glottis. Estimating the quotient
      instead of measuring only the MPT, we avoid the influence of respiratory
      alterations in the results. We evaluated the utility of the s/z ratio as a
      clinical indicator of laryngeal pathology in 72 patients with organic vocal cord
      pathology. We compared the results of the s/z ratio to the degree of glottic
      closure defect, measured by videolaryngostroboscopy. S/z ratio in 22 normal
      speaking subjects was also measured. S/z ratio in normal-speaking subjects was
      nearly 1.0. When a glottic closure defect was present, the ratio was over 1.4.
      Organic lesions that difficult glottic closure, produce a decrease of air flow
      resistance and, therefore, a shortening of the MPT of the vowel sounds.

PMID- 7734165
TI  - [Verrucous carcinoma of the larynx].
AB  - The present work shows a retrospective study of 11 cases of verrucous carcinoma
      of the larynx from data collected at Marques de Valdecilla Hospital for ten
      years. All patients were males. Glottis was the most common site involved (10
      cases). Eight patients were treated with partial surgery and in two cases total
      laryngectomy was performed. One patient refused treatment. Five-year survival
      rates were 100% in the ten patients treated. Verrucous carcinoma of the larynx is
      a well differentiated variant of squamous cell carcinoma. Surgical treatment is
      necessary for the primary lesion without neck dissection. Radiotherapy is not
      indicated because the possibility of anaplastic transformation. Prognosis is
      excellent after surgical treatment.

PMID- 7734166
TI  - [Primary rhabdomyosarcoma of the temporal bone].
AB  - A case of rhabdomyosarcoma of the temporal bone in a six-year-old girl is
      reported. Updated literature and the main therapeutical approaches are reviewed.

PMID- 7734167
TI  - [Maxillary ameloblastoma].
AB  - Ameloblastoma is a tumor constituted by proliferative odontogenic epithelium
      that, in 20% of the cases, originates in the maxilla. Clinical and radiologically
      it can be multicystic, monocystic and peripheral. Although it is considered
      benign, the tumor may grow slowly, with intracranial invasion or distant spread.
      In the present work we analyze our experience and the literature on the field,
      and, as a conclusion, we recommend initial complete surgical excision.

PMID- 7734168
TI  - [Thrombophlebitis of the cavernous sinus secondary to polysinusitis. Report of a
      new case].
AB  - Cavernous sinus thrombophlebitis syndrome is uncommon nowadays. Despite the wide
      range of antimicrobial agents it carries a high mortality. The disease frequently
      arises from infection of face, mouth, nose and paranasal sinuses, reaching the
      cavernous sinus by venous spread. Involvement of adjacent anatomic structures
      accounts for most of the clinical findings. Meningeal involvement, bilateral
      orbital edema and ocular cranial nerves palsy are very helpful in the
      differential diagnosis. Streptococcus spp., Staphylococcus spp., Haemophilus
      influenzae and anaerobic organisms are considered to be the most frequent
      etiological agents. In the present paper we report a case of cavernous sinus
      thrombophlebitis following left side polysinusitis. The patient presented with
      the main clinical features of the syndrome along with Streptococcus equisimilis
      and Fusobacterium necrophorum bacteremia. Urgent surgery of infected sinuses and
      appropriate antibiotic therapy led to a favorable outcome. The patient made and
      excellent progress and was discharged completely recovered two weeks after
      admission.

PMID- 7734169
TI  - [Solitary extramedullary plasmacytoma of the larynx. Apropos of a case].
AB  - The present paper shows a case of solitary extramedullary plasmocytoma of the
      larynx. It is important to know the limits of this process in order to rule out a
      multiple myeloma. After a literature review, emphasis is made in the necessity of
      a very long term patient's follow up, since recurrences may occur some years
      after the initial diagnostic.

PMID- 7734170
TI  - [Hypertrophic osteoarthropathy in a patient with nasopharyngeal carcinoma].
AB  - A clinic-pathological study of a 12 year-old male diagnosed of non-differentiated
      nasopharyngeal carcinoma (NPC) was carried out. The patients presented secondary
      hypertrophic osteoarthropathy prior to the development of lung metastases.
      Hypertrophic osteoarthropathy is a clinic-radiological syndrome characterized by
      a neoformation of periosteal bone, fundamentally located in long bones and distal
      ends of metacarpal bones. Polyarticular and synovial involvement is also
      observed. Association between NPC and hypertrophic osteoarthropathy is uncommon
      and appears to suggest the existence of metastatic spread (probably to the lung),
      particularly in young patients.

PMID- 7734171
TI  - [Reconstructive and functional surgery of the middle ear (review of 276 cases)].
AB  - The present work presents the review of 276 cases that underwent the following
      surgeries: 62 myringoplasties, 176 tympano-ossicular reconstructions, 9
      functional second look surgery and 29 tympanoplasties with ossiculoplasties.
      Regarding two different parameters, results were as follows: 1) New eardrum after
      one-year evolution: 94% were complete, 3.8% were perforated and 2.3% had
      cholesteatoma pearls. 2) Hearing level after one-year evolution: 33% was the
      same, 29% gained less than 15 dB, 26.8% gained between 15 and 30 dB, and 11.2%
      gained over 30 dB.

PMID- 7734172
TI  - [Intraparotid facial neurilemmoma].
AB  - Neurilemmomas or schwannomas are known to arise from the sheath of peripheral
      nerves. Out of the cranial nerves, the eighth nerve is the most frequently
      involved. Neurilemmomas arising from the facial nerve are are, and they usually
      affect the intratemporal portion of the nerve. Its location in the intraparotid
      portion is very uncommon. The case of a patient having an intraparotid mass is
      shown. After surgery it was found to be a neurilemmoma of the facial nerve. These
      tumors manifest as an asymptomatic mass in the parotid gland. Most of the times,
      diagnosis is made postoperatively. It is necessary to remove all the tumor with
      the caution to preserve the original nerve.

PMID- 7734173
TI  - The relationship between odontoblasts and immunocompetent cells during
      dentinogenesis in rat incisors: an immunohistochemical study using OX6-monoclonal
      antibody.
AB  - The relationship between odontoblasts and class II major histocompatibility
      complex (MHC) antigen-expressing cells in the process of dentinogenesis was
      studied in rat lower incisors, employing immunohistochemistry using OX6
      monoclonal antibody. The dental pulp contained numerous OX6-immunopositive cells
      that varied in morphology from dendritic to spindle under physiological
      conditions. Under the electron microscope, these immunopositive cells shared
      common cytoplasmic features, i.e., multivesicular bodies and characteristic fine
      tubulovesicular structures in their cytoplasm. At the early stage of
      dentinogenesis, OX6-immunopositive cells, presumably of the immature type, were
      located in the subodontoblastic layer. During active dentin formation, the OX6
      immunopositive cells increased in number and appeared in the odontoblast layer,
      associating intimately with fenestrated capillaries situated close to the
      predentin. These cells showed a dendritic appearance and possessed various sizes
      of multivesicular bodies and characteristic fine tubulovesicular structures, but
      never contained typical phagosomes. On the other hand, immunopositive macrophages
      characterized by typical phagosomes tended to occupy the central portion of the
      pulp. The results suggest that most, if not all, OX6-immunopositive cells
      situated deep in the odontoblast layer are dendritic cells playing a role in the
      defense system of the dental pulp against antigenic molecules arriving from the
      circulation via the fenestrated capillaries. The increasing number of OX6
      immunopositive or immunonegative macrophages appearing near the incisal end of
      the tooth is thought to be involved in the elimination of degenerated
      odontoblasts.

PMID- 7734174
TI  - The effects of subcutaneous injections of glucocorticoids on amoeboid microglia
      in postnatal rats.
AB  - Subcutaneous injections of glucocorticoids into postnatal rats resulted in a
      drastic reduction in the number of amoeboid microglial cells in the corpus
      callosum as shown by their labelling with the monoclonal antibodies of the OX
      series, ED1, lectin and rhodamine isothiocynate (RhIc). In rats receiving 2 or 3
      injections of glucocorticoids and killed at the age of 4 or 7 days, between 40 to
      60% of the callosal amoeboid microglial cells were depleted when compared with
      the corresponding control animals. The cells that survived the glucocorticoid
      treatments became ramified, while those in the controls of the same age group
      remained round or amoeboidic. In rats killed at 2 or 3 weeks of age, the
      microglia became extremely ramified with a concomitant diminution in their
      immunostaining, particularly in the glucocorticoid-injected rats. In rats
      receiving glucocorticoid injections along with RhIc, the RhIc-laden amoeboid
      microglia appeared round and amoeboidic and were intensely stained with OX-42,
      suggesting their activation and upregulation of complement type 3 receptors when
      compared with rats receiving only glucocorticoids. Compared with the control,
      cellular proliferation continued in rats given glucocorticoid injection as
      indicated by the occurrence of many bromodeoxyuridine-labelled cells in the
      corpus callosum at the age of 6 days. Ultrastructural studies confirmed the
      presence of mitotic cells identified as amoeboid microglia because of their
      labelling with isolectin. A striking ultrastructural feature in glucocorticoids
      injected rats was the wide occurrence of amoeboid microglial cells that had
      ingested a variable number of lectin-labelled cells. It is concluded from this
      study that the drastic reduction of amoeboid microglia after glucocorticoid
      injections can be attributed to the suppression of their precursor cells,
      monocytes. Another possible explanation is the acceleration of their degeneration
      process, probably greatly enhanced by glucocorticoids; the degenerating amoeboid
      microglia were readily eliminated by the surviving amoeboid microglial cells
      through endocytosis. Glucocorticoids also accelerated the maturation process of
      the persisting amoeboid microglia to become ramified in form.

PMID- 7734175
TI  - Arginine vasopressin- and oxytocin-like immunoreactive neurons in the
      hypothalamic paraventricular and supraoptic nuclei of streptozotocin-induced
      diabetic rats.
AB  - This study describes ultrastructural and morphometric changes in the arginine
      vasopressin (AVP)-like immunoreactive and oxytocin (OT)-like immunoreactive
      neurons in the hypothalamic paraventricular nuclei (PVN) and supraoptic nuclei
      (SON) of streptozotocin-induced diabetic rats at 1-12 months post-diabetes. At 1
      6 months post diabetes, both AVP-immunoreactive and OT-immunoreactive neuronal
      somata were hypertrophied in the PVN and SON. These neuronal somata contained
      highly dilated rough endoplasmic reticulum in the cytoplasm. The reaction product
      for AVP as well as OT localization was dispersed throughout the cytoplasm and
      cell nucleus, but not within the nucleolus. Moreover, the reaction product
      appeared to be studded onto the ribosomes on dilated cisterns of the endoplasmic
      reticulum. At 9-12 months post-diabetes, both AVP-immunoreactive and OT
      immunoreactive dendrites contained dilated endoplasmic reticulum, autophagic
      vacuoles, lipid bodies, microtubules, membranous bodies and occasionally swollen
      mitochondria. Labelled hypertrophied axonal profiles containing neurosecretory
      granules, autophagic vacuoles, membranous bodies and tubulovesicular elements
      were also observed in the neuropil. Morphometric study showed that both AVP
      immunoreactive and OT-immunoreactive neuronal somata of the PVN and SON in the
      diabetic rats were markedly hypertrophied at all the time intervals examined. It
      is concluded that the morphometric changes observed represent hyperactivity of
      both AVP- and OT-immunoreactive neurons, while the concurrent ultrastructural
      changes observed at later stages may be indicative of degeneration.

PMID- 7734176
TI  - Vagal afferent nerve endings in the trachealis muscle of the dog.
AB  - Nerve endings in the canine tracheal muscle were examined by light microscopy
      after immunohistochemical staining with an antibody against neurofilament
      protein, and by transmission electron microscopy. The endings were found to
      consist of accumulations of ramified axon terminals. The endings ranged from 100
      400 microns in maximal length to 30-80 microns in minimal length. Most of the
      endings were arranged parallel to the smooth muscle strands, with 80-90% located
      in the membranous wall and densely distributed in the cranial region of the
      trachea. The endings were covered with a connective tissue sheath that contained
      fine elastic fibers. Ultrastructural examination revealed that axon terminals
      were derived from myelinated axons, and were located in a connective tissue
      sheath among the smooth muscle cells. Each axon terminal contained large numbers
      of mitochondria, lysosomes, neurofilaments, glycogen granules and synaptic
      vesicle. Incomplete coverage by Schwann cells and multiple layers of basal lamina
      were observed around the axon terminals. Surgical denervation revealed that the
      endings were of vagal origins. The access pathway to the endings in about one
      third of the cranial region of the trachea appeared to be the cranial laryngeal
      nerve, while in about two-thirds of the caudal region, this appeared to be the
      tracheal branches derived from the recurrent laryngeal nerve and/or from the
      vagosympathetic trunk.

PMID- 7734177
TI  - Ultrastructural identification of Ricinus communis agglutinin-1 positive cells in
      primary dissociated cell cultures of human embryonic brain.
AB  - While Ricinus communis agglutinin 1 (RCA-1) can be used as a specific marker to
      study the development and differentiation of microglial cells in human
      embryogenesis, little is known about the structural heterogeneity and nature of
      RCA-1+ cells. To analyse the structural peculiarities of RCA-1+ cells, we have
      used primary dissociated cultures of human embryonic brain. These have been used
      as models for investigating many of the aspects of central nervous system (CNS)
      HIV infection. We have shown that primary dissociated cultures from human embryos
      as young as 10 weeks gestation contain RCA-1+ cells. The RCA-1+ cells exist in
      two forms, those without (type I) and those with (type II) processes. The former
      have a poorly developed ultrastructure, while the latter have well developed
      ultrastructural features, such as rough endoplasmic reticulum with short
      cisternae, abundant ribosomes, mitochondria, lysosomes and vacuoles. Furthermore,
      some of these cells with processes have well developed cytoskeletal features. In
      this paper, the classification of RCA-1+ cells of embryonic human brain is
      considered and their morphology compared to microglia identified in rodent CNS.

PMID- 7734178
TI  - Neurons with intensely negatively charged extracellular matrix in the human
      visual cortex.
AB  - Neurons in the human visual cortex were demonstrated to possess an intensely
      negatively charged surface coat which was stained with cationic iron colloid and
      aldehyde fuchsin. Digestion with hyaluronidase eliminated both the iron colloid
      and fuchsin stainings of the coats. Treatment with chondroitinase ABC,
      heparitinase and keratanase eliminated the iron colloid staining of the coats,
      but did not interfere with the fuchsin staining. Electron microscopy of ultrathin
      sections revealed that the cationic iron particles were preferentially deposited
      in the perineuronal tissue spaces. These findings indicate that the surface coats
      consist of sulfated proteoglycans, which, as an extracellular matrix, occupy the
      perineuronal tissue spaces. This study further demonstrates that neurons with
      such surface coats are identical with neurons labeled with lectin Vicia villosa
      agglutinin. The cell surface glycoproteins reactive to this lectin may not be the
      structural elements of the sulfated coats since the lectin labeling was not
      interrupted by the hyaluronidase digestion.

PMID- 7734179
TI  - Electron microscopic observation of ciliated cysts in the human oviduct
      epithelium.
AB  - Intracytoplasmic ciliated cysts were observed in the human oviduct epithelium.
      Transmission electron microscopy demonstrated the occurrence and fine structure
      of those cysts, clarifying the process of their opening to the oviduct lumen.
      When located apically in the epithelial layer, the cysts moved upwards and
      expanded into the oviduct lumen, leaving a thin cytoplasmic layer, until they
      broke into the oviduct lumen. In contrast, basally-lying cysts did not move but
      were approached by an invagination of the epithelial surface which extended
      toward the cell base. The cysts were then broken onto the bottom of the
      invagination and consequently opened into the oviduct lumen. Although the
      intracytoplasmic ciliated cysts have previously been considered to be formed by
      abnormal ciliogenesis, the present study indicates that, at least in the human
      oviduct, they contribute to the formation of the normal ciliated border of the
      epithelium.

PMID- 7734180
TI  - Histological localization of the sweet taste receptor in rat taste buds by the
      use of gurmarin, a sweet taste-suppressing peptide.
AB  - The binding site of gurmarin, a peptide inhibiting the sweet-taste sensation, was
      studied in taste buds in rat circumvallate papillae by means of a histochemical
      technique. Frozen sections of tongues were incubated with gurmarin conjugated
      with biotin and thereafter examined with a light microscope. Positive reactivity
      for the peptide was localized to the taste hairs, the apical projections of taste
      bud cells. The reaction appeared in about 10% of the circumvallate taste buds
      examined. As electrophysiological studies indicate that gurmarin suppresses the
      sweet-taste sensation at the level of reception, the present study suggests that
      the receptor for sweet taste is located on the taste hairs, and, furthermore, is
      present only in a certain, limited number of the taste buds.

PMID- 7734181
TI  - Immunohistochemical localization of vacuolar H(+)-ATPase in osteoclasts of rat
      tibiae.
AB  - The localization of vacuolar H(+)-atpASE (V-ATPase) in osteoclasts of rat tibiae
      was examined immunohistochemically using antibodies to 57 kD and 72 kD subunits
      of V-ATPase, with confocal laser scanning microscopy and transmission electron
      microscopy. The two antibodies showed similar immunoreactivities in osteoclasts.
      We distinguished three patterns of immunoreactivity in osteoclasts: The first
      pattern was that immunoreactivity was diffusely detected in cytoplasm of
      osteoclasts; The second one was that osteoclasts showed intense immunoreactivity
      in their regions contacting with bone surface; and the last was that little
      immunoreactivity was seen in osteoclasts. Post-embedding methods with protein A
      gold complex revealed that the subunits of V-ATPase were localized not only on
      the membranes of the ruffled borders of osteoclasts, but also around the Golgi
      apparatus and accumulated tubular lysosomes. These findings suggest that: 1)
      immunoreactive patterns for V-ATPase in osteoclasts reflect the polarity and
      activity of osteoclasts; and 2) V-ATPase on ruffled borders may be transported
      through tubular lysosomes.

PMID- 7734182
TI  - Update on long-term symptomless HIV type 1 infection in recipients of blood
      products from a single donor.

PMID- 7734183
TI  - Limited sequence diversity of the HIV type 1 protease gene from clinical isolates
      and in vitro susceptibility to HIV protease inhibitors.
AB  - Proviral DNAs from 3 laboratory strains and 21 clinical isolates of HIV-1 were
      extracted from infected cells after proteinase K digestion and the protease gene
      was PCR amplified and sequenced directly by the Sanger method. In vitro
      susceptibilities of the virus isolates to protease inhibitors were determined by
      the ACTG/DoD consensus assay. Four different HIV protease inhibitors were tested
      including P9941, a C2 symmetrical diol (Du Pont-Merck); A80987, an asymmetric
      mono-ol (Abbott); XM323, a cyclic urea (Du Pont-Merck); and Ro31-8959, an
      asymmetric hydroxyethylene isostere (Roche). Maximum sequence variation was 10%
      at both the nucleic and amino acid levels. Purine-purine substitutions were most
      common. Five noncontiguous regions were conserved across all isolates and
      corresponded to amino acids 1-9 (amino terminal), 21-32 (catalytic site), 47-56
      ("flap" region), 78-88 (substrate-binding region), and 94-99 (carboxy terminal).
      All clinical isolates demonstrated in vitro susceptibility to the protease
      inhibitors. There was no significant difference between the susceptibility of the
      reference strains and the clinical isolates. These data suggest that the variable
      regions of protease do not contain sites that are important for interactions with
      the inhibitors tested.

PMID- 7734184
TI  - HIV-1 infection of the thymus: evidence for a cytopathic and thymotropic viral
      variant in vivo.
AB  - As thymocyte infection may represent one of the mechanisms responsible for CD4+ T
      lymphocyte depletion in HIV-1-infected individuals, we studied the occurrence of
      HIV-1 infection in the thymus in vivo. Thymus (THYPD) and peripheral blood
      (PBLPD) primary viral isolates were obtained from an HIV-1-infected patient;
      restriction pattern analysis revealed the presence of a viral variant (THY) in
      the thymus isolate, from which biological viral clones containing this variant
      were obtained by limiting dilution infection of Molt-3 cells. The biological
      phenotype of the viral isolates and THY clones was studied in different cell
      lines and primary cultures. PBLPD, THYPD, and THY clones could efficiently infect
      T cell lines; the thymic variant showed a higher cytopathic activity in T cell
      lines, and a higher replication capacity in both unfractionated and CD4+CD8(+)
      enriched primary thymocytes. Sequence analysis of the viral population patterns
      in vivo confirmed the presence of the THY variant in the thymic compartment, and
      revealed that the degree of V3 loop heterogeneity was higher in the thymocytes of
      the patient than in the peripheral blood lymphocytes. In addition to confirming
      thymocyte infection in vivo, our data also indicate that a differential
      distribution of viral variants may occur among different body compartments in a
      single individual; the emergence of cytopathic and tissue-specific variants in
      the thymus may play a relevant role in the pathogenesis of HIV-1 disease.

PMID- 7734185
TI  - Inhibition of human immunodeficiency virus type 1 integrase by a hydrophobic
      cation: the phenanthroline-cuprous complex.
AB  - The human immunodeficiency virus type 1 integrase (HIV-1 integrase) is required
      for integration of a double-stranded DNA copy of the viral RNA genome into a host
      chromosome and for HIV replication. We have examined the effects of 2:1 1,10
      phenanthroline-cuprous complexes on purified HIV-1 integrase. Although the
      uncomplexed phenanthrolines are not active below 100 microM, four of the cuprous
      complexes (neocuproine, 4-phenyl neocuproine, 2,3,4,7,8,9-hexamethyl
      phenanthroline, and 2,3,4,7,8-pentamethyl phenanthroline) have a 50% inhibitory
      concentration (IC50) for integration ranging between 1 and 10 microM.
      Disintegration is also inhibited by these phenanthroline-cuprous complexes at
      slightly higher concentrations (between 10 and 40 microM). Dialysis experiments
      showed that the inhibition is reversible and kinetic analyses revealed that the
      mode of inhibition by these cuprous complexes appears to be noncompetitive with
      respect to the substrate DNA. Consistent with these findings, binding assays
      demonstrate that, although these complexes can inhibit binding to DNA at high
      concentrations, they do not inhibit binding of integrase to the DNA substrate at
      their IC50 values. Because these complexes do not bind to B-DNA below 50 microM,
      inhibition via binding to a specific region on the enzyme was examined. Using
      deletion mutants of integrase, it was determined that neither the amino-terminal
      (zinc finger) nor the carboxy-terminal (DNA-binding) integrase domain is required
      for inhibition by the phenanthroline-cuprous complexes. Therefore, inhibition via
      binding to the enzyme catalytic core or to the interface between the enzyme and a
      noncanonical DNA structure generated during the enzymatic reaction is the
      probable mechanism. These results suggest the utility of neocuproine-cuprous
      complexes in developing inhibitors of HIV-1 integrase as well as probes for drug
      binding sites and enzymatic reaction mechanism.

PMID- 7734186
TI  - Bathophenanthroline disulfonate and soluble CD4 as probes for early events of HIV
      type 1 entry.
AB  - We report here that a metalloprotease inhibitor, bathophenanthroline disulfonate
      (Bphe-ds), neutralizes both laboratory-adapted and primary strains of HIV-1.
      Presaturation of Bphe-ds with zinc does not alter its neutralizing activity,
      suggesting that the metal-chelating ability of Bphe-ds is not required for
      neutralization. Bphe-ds blocks infection of CD4+ cells at the stage of viral
      entry, not through a direct viricidal effect, but by interfering with both
      binding and postbinding events. This drug interacts with HIV-1 envelope, blocking
      almost completely the binding of three MAbs that recognize epitopes overlapping
      the CD4-binding site on gp120, but has no effect on the binding of MAbs directed
      to the cellular receptor CD4. The exposure of epitopes in the V2 and V3 but not
      C5 domains of gp120 is partially decreased in the presence of Bphe-ds, suggesting
      that the drug induces conformational changes in the envelope glycoprotein(s).
      Binding of both virions and soluble gp120 to CD4+ cells is inhibited by this drug
      in a dose-dependent manner. This contrasted with the effects of soluble CD4,
      which actually increased binding of virions to cells at 4 degrees C, while
      inhibiting the binding of soluble gp120. Bphe-ds also increases shedding of gp120
      from cells infected with HIV-1IIIB. Thus, Bphe-ds appears to be an envelope
      directed inhibitor of HIV-1 that neutralizes HIV-1 infectivity via multiple
      mechanisms.

PMID- 7734187
TI  - Supplementation of N-acetylcysteine fails to increase glutathione in lymphocytes
      and plasma of patients with AIDS.
AB  - Because glutathione (GSH) in plasma and lymphocytes of HIV-infected patients is
      low, adjunct therapy with N-acetylcysteine (NAC) to restore GSH homeostasis has
      been proposed. To investigate the effect of NAC on the GSH status we treated six
      patients with AIDS with 1.8 g/day of NAC for 2 weeks. During treatment the plasma
      concentration of cysteine, a precursor for GSH synthesis, increased
      significantly. Nevertheless, there was no significant increase in GSH in plasma
      and peripheral blood mononuclear cells. The failure of sulfhydryl supplementation
      to increase GSH suggests that the low concentrations of the tripeptide are not
      the result of an increased consumption secondary to an oxidant stress, but rather
      the consequence of a decreased rate of synthesis of GSH in HIV infection.

PMID- 7734188
TI  - Cell surface phenotypic changes induced in H9 T cells chronically infected with
      HTLV type I or HIV type 1 or coinfected with the two viruses.
AB  - To investigate whether HTLV-I infection, HIV-I infection, or HIV-I infection of
      HTLV-I-infected cells affect the expression of cellular surface molecules, an
      HTLV-I-infected T cell line derived from the H9 T cell line was established
      (H36). H9 cells uninfected or infected with HTLV-I were then infected with HIV-1.
      We have compared the density of different surface markers on these three infected
      H9 T cell lines. These markers consist of T cell-specific antigens (CD2, CD3,
      CD4, and CD8), activated T cell antigens (CD25 and CD71), major
      histocompatibility complex (MHC) antigens (class I and II), and adhesion
      molecules (LFA-1 and ICAM-1). The experiments reported in this article show that
      chronic HTLV-I infection, HIV-1 infection, and HIV-1 infection of HTLV-I-infected
      T cells modulate the expression of several immunologically important cell surface
      antigens. The nature and the extent of T lymphoid cell phenotypic modulation
      depend on the infecting virus. Furthermore, HTLV-I and HIV-1 interact with each
      other in the phenotypic modulation of coinfected cells.

PMID- 7734189
TI  - Markers of foamy virus infections in monkeys, apes, and accidentally infected
      humans: appropriate testing fails to confirm suspected foamy virus prevalence in
      humans.
AB  - Foamy viruses (FVs) persist in healthy individuals of various mammalian species,
      including nonhuman primates. Laboratory markers of FV infection are (1) virus in
      throat epithelium or peripheral blood lymphocytes (PBLs), (2) proviral DNA
      sequences in PBLs and various solid organs, and (3) antibodies reactive to viral
      antigens on Western blots, in radioimmunoprecipitation tests, and in
      immunofluorescence assays. Using PCR and serological tests, we readily detected
      FV markers in naturally infected African green monkeys, rhesus monkeys, and
      chimpanzees, as well as in accidentally infected humans. Transmission of simian
      foamy viruses to humans (by bite or inadvertent laboratory infection) leads to
      viral markers, without affecting the recipient. Reports on FV-associated clinical
      disorders (e.g., thyroid or neurological) have remained controversial. In this
      study we failed to detect, by PCR, viral sequences in the samples from 223
      patients, including 16 HIV-infected Africans, 46 Graves' disease patients, and 28
      patients with the de Quervain's thyroiditis. Evaluation of 2688 sera from
      suspected high-risk areas (e.g., Central and East Africa, or high-risk groups
      such as HIV-infected individuals and patients with AIDS, thyroid, and
      neurological disorders) did not reveal FV-specific antibodies in a single case.
      Previously reported FV seroprevalence in various populations has never been
      verified by appropriate confirmatory tests. The strain of "human foamy virus" has
      remained a unique isolate. In conclusion, FVs are unlikely--at present--to
      circulate in human populations.

PMID- 7734190
TI  - Vertical transmission of feline immunodeficiency virus.
AB  - We studied vertical transmission of feline immunodeficiency virus (FIV) to
      determine whether it might provide a model with which to study intervention
      strategies for mother-to-offspring transmission of human immunodeficiency virus
      (HIV). We found that pregnant cats acutely infected with FIV (FIV-CSU-2771)
      transmitted the virus to their offspring via both prenatal and postnatal routes.
      In utero transmission led to several pathogenic consequences including arrested
      fetal development, abortion, stillbirth, subnormal birth weights, and birth of
      viable, virus-infected, and asymptomatic but T cell-deficient kittens. Postnatal
      milk-borne FIV transmission was demonstrated by the presence of cell-free and
      cell-associated virus in colostrum and milk and through a foster-nursing
      experiment. The potential for intrapartum FIV transmission was documented by
      frequent virus isolation from vaginal wash cells in both the pre- and postpartum
      periods. FIV transmission was efficient during acute maternal infection, leading
      to an overall infection rate of 70%. We conclude that FIV vertical transmission
      may be a useful model with which to evaluate intervention strategies for HIV
      transmission from mother to child.

PMID- 7734191
TI  - New crown motif of an HIV-1 V3 loop sequence from a Ugandan AIDS patient.

PMID- 7734192
TI  - Uncommon gp120 cysteine residues found in primary HIV-1 isolates.

PMID- 7734193
TI  - Sequential determination of viral load and phenotype in human immunodeficiency
      virus type 1 infection.
AB  - Detailed studies of HIV viral load and phenotype were performed on sequentially
      cryopreserved peripheral blood mononuclear cells (PBMCs) from eight infected
      individuals followed in the Los Angeles Multicenter AIDS Cohort Study. Three
      individuals remained clinically and immunologically stable over a 5- to 8-year
      period, three demonstrated precipitous and two gradual declines in CD4+ T
      lymphocytes. Viral load in PBMCs was quantitated by limiting dilution culture and
      DNA PCR, while minimally passaged viral isolates were studied for their ability
      to induce syncytium formation in vitro and, when relevant, sensitivity to
      zidovudine (ZDV). Viral burden remained relatively low in those who remained
      clinically and immunologically stable, while increasing substantially in all five
      individuals who experienced a decline in CD4+ T lymphocytes. Two subjects were
      noted to have a switch from non-syncytium-inducing (NSI) to syncytium-inducing
      (SI) isolates immediately preceding a precipitous decline in CD4+ T lymphocytes,
      while the third individual who experienced such a decline and the two who had
      gradual declines did not develop SI isolates. Moreover, of the three subjects who
      experienced a decrease in CD4+ T lymphocyte number and were given ZDV during the
      study period, none were noted to develop resistance to this agent. In summary,
      the virology in clinically and immunologically stable individuals was
      characterized by relatively low viral burden in PBMCs and a predominance of NSI
      isolates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734194
TI  - Constitutive expression of human immunodeficiency virus type 1 tat gene inhibits
      interleukin 2 and interleukin 2 receptor expression in a human CD4+ T lymphoid
      (H9) cell line.
AB  - Human immunodeficiency virus (HIV-1) tat, a trans-activator of the HIV long
      terminal repeat, is essential for HIV replication and causes inhibition of
      antigen-mediated T cell proliferation. To understand the mechanism of inhibition
      of T cell proliferation, we have investigated the regulation of IL-2 production
      and its receptor expression on a human CD4+ T lymphoid cell line (H9) transfected
      with HIV-1 tat gene. When cells were activated by mitogens, as compared to
      control cells, a significant decrease in both IL-2 mRNA and protein was observed
      in tat-transfected cells. Similarly, mitogen-induced IL-2R alpha and IL-2R beta
      mRNA and surface expression of IL-2R alpha and IL-2R beta chains were also
      significantly decreased in tat-transfected cells compared to control cells. Only
      IL-2 receptor density was decreased; the affinity of the ligand for the receptor
      appeared to be unchanged. In contrast to our previous studies with B
      lymphoblastoid cell line (Puri RK and Aggarwal BB: Cancer Res 1992; 52:3787
      3790), IL-4R expression was unaltered by HIV tat transfection in the H9 T cell
      line, indicating a cell type-specific phenomenon. Owing to the central role of IL
      2 immunoregulation, our data suggest that immunosuppressive effects of HIV-1 tat
      may be mediated at least in part through the inhibition of both IL-2 production
      and IL-2 receptor expression.

PMID- 7734195
TI  - X irradiation-induced transcription from the HIV type 1 long terminal repeat.
AB  - It has been previously shown in vitro and in vivo that the human immunodeficiency
      virus type 1 can be dramatically enhanced by certain heterologous viral,
      chemical, and physical (ultraviolet irradiation) agents. A common denominator
      shared by these agents is their ability to cause stress responses in cells. To
      analyze if a similar effect could occur by X irradiations, we tested the in vitro
      effect of X rays on HIV LTR-directed gene expression. The results demonstrate
      that the HIV-1 LTR is activated by X irradiation in a dose- and time-dependent
      manner, in all cell types tested, including epitheloid, fibroblast, and lymphoid
      cell lines. This study raises the possibility that exposure of AIDS patients to
      ionizing radiation (e.g., during treatment of epidemic Kaposi's sarcoma) could
      play a role in the activation of HIV-1 in vivo.

PMID- 7734196
TI  - Superinfection of a defective human immunodeficiency virus type 1 provirus
      carrying T cell clone with vif or vpu mutants gives cytopathic virus particles by
      homologous recombination.
AB  - The partially CD4-expressing T cell clone, Vpr-1, which carries a latent vpr
      defective HIV-1 genome and expresses HIV-1 Nef protein only, was permissive to
      superinfection by HIV-1. Superinfection of Vpr-1 with vif- or vpu-defective
      mutants, which were noncytopathic, reactivated the vpr-defective virus and led to
      homologous recombination and cytopathogenesis. The data provide an experimental
      model for homologous recombination being an important mechanism whereby HIV-1
      acquires genetic heterogeneity, and when occurring among defective virus in vivo
      bestows novel biological activities and virulence.

PMID- 7734197
TI  - Ultrastructural evidence of an interaction between Env and Gag proteins during
      assembly of HIV type 1.
AB  - Assembly and budding of retroviruses is believed to involve a complex interaction
      of envelope and capsid proteins at the host cell membrane. The nature of these
      interactions is, however, incompletely understood. Studies of the topography of
      the surface of HIV-1 have shown that the envelope glycoprotein projections
      (knobs) are arranged in a T = 7 levo rotational symmetry. Similarly, an
      icosahedral structure has been suggested for the p17 matrix of HIV-1. In an
      effort to investigate whether there is a structural interaction between these
      molecules, virions whose maturation was blocked by an inhibitor of HIV protease
      were studied using cytochemistry, morphometry, and 2D fast Fourier transform
      image enhancement. Analysis of the relationship between core morphology and the
      topographic distribution of envelope glycoprotein projections on HIV-1 provided
      structural evidence of an interaction between Env and Gag proteins. Furthermore,
      image enhancement revealed a periodic substructure in the Pr55gag plaque. Taken
      together, the data suggest an interaction between Pr55gag and the gp120-gp41
      complex during assembly and budding of HIV-1. This interaction may, in part,
      contribute to determining the amount of Env glycoprotein that will be
      incorporated into a virion, and therefore play a role in the biology of HIV-1.

PMID- 7734198
TI  - Oligomerization of the HIV type 2 Nef protein: mutational analysis of the heptad
      leucine repeat motif and cysteine residues.
AB  - The human immunodeficiency virus type 2 (HIV-2) Nef protein expressed in
      Escherichia coli forms highly stable homooligomeric complexes in vitro.
      Similarly, the native protein synthesized in the persistently infected H9 T cell
      line also forms stable homooligomers in vivo. To determine whether homooligomer
      formation is mediated by the leucine zipper-type sequence located in the middle
      region of the protein, site-directed mutagenesis was used to introduce double and
      triple point mutations at heptad leucine positions L1, L2, and L4 within the HIV
      2NIHZ Nef protein sequence. Here, we show that substitution of a serine residue
      for the L1 (residue 108) and L2 (residue 115) heptad leucines, and a glutamine
      residue for the L4 (residue 129) heptad leucine, did not prevent Nef homooligomer
      formation in vitro. However, a more drastic substitution of alpha-helix-breaking
      proline residue for the L2 and L4 heptad leucines significantly abrogated ability
      of the protein to form stable homooligomers. In addition, because significantly
      higher levels of the Nef oligomers were consistently observed under the
      nonreducing SDS-PAGE condition, site-specific mutagenesis was also used to
      examine the role of cysteine residues in generating disulfide-linked Nef dimers
      in vitro. Here, we also show that single cysteine-to-glycine substitutions at
      positions 28, 32, or 55 drastically reduced covalent Nef dimer formation and
      thermal stability of the Nef protein in vitro. Therefore, these results
      demonstrate that the leucine zipper-type motif in the HIV-2 Nef protein mediates
      stable homooligomer formation in vitro, and also establish a role for covalent
      disulfide bonds in the formation of linked Nef dimers and thermal stability of
      the monomer Nef in vitro.

PMID- 7734199
TI  - Enhanced proteolytic processing of the human immunodeficiency virus type 1
      envelope protein in murine Ltk(-) cells.
AB  - Proteolytic processing of the human immunodeficiency virus type 1 (HIV-1)
      envelope (Env) precursor glycoprotein (gp160) to produce the mature gp120 and
      gp41 proteins is required for virus infection and virus-induced cell fusion. It
      has also been suggested that cleavage of gp120 at the immunodominant V3 loop
      region is required for virus-to-cell and cell-to-cell fusion. In this
      investigation we have studied the proteolytic processing of the HIV-1 Env in
      cells of various origins (human, monkey, and mouse) infected with a vaccinia
      virus recombinant expressing the entire gp160 protein (VV-env-1). We have
      observed that in murine Ltk(-) cells, in addition to the proteolytic cleavage of
      gp160 at the gp120/gp41 site, there is also extensive intracellular proteolytic
      processing of gp160 at the V3 loop and at a novel site located at the C terminus
      of gp41. Similar proteolytic processing of the Env precursor was observed after
      treatment of extracts of VV-env-1-infected monkey cells with thrombin, a trypsin
      like protease that has been shown to cleave the gp120 at the V3 loop. Our
      findings suggest that murine Ltk(-) cells could be a good model system for
      structural studies of Env with different HIV isolates and in searches for
      proteinase inhibitors that could prevent HIV-1 infection of susceptible cells by
      blocking proteolysis of Env.

PMID- 7734200
TI  - Lectin-mediated effects on HIV type 1 infection in vitro.
AB  - Lectins with specificity for terminal mannose residues and anti-mannan antibodies
      neutralize HIV-1 infection in vitro. This is assumed to be caused by binding of
      the agents to the viral glycoproteins. In this study we show that one such agent,
      the Galanthus nivalis lectin (GNA), also blocks infection at the target cell
      level. To explore the effect of GNA on HIV infection we used the two HIV-1
      isolates LAV and NDK, representing in the first case a prototype virus and in the
      latter case a highly cytopathic virus, which spreads preferentially via cell-to
      cell contact. MT-4 cells were used as target cells and infection was determined
      from the occurrence of syncytia. Cell-to-cell infection was studied with CEM
      cells persistently infected with the two virus isolates. GNA, at concentrations
      in the nanogram per milliliter range, neutralized the HIV-1 isolates LAV, NDK,
      and MN as well as HIV-2ROD. Pretreatment of cells with the lectin, before
      addition of virus, or of infected cells, also blocked infection. This effect was
      more pronounced with HIV-1NDK than with HIV-1LAV. Mannosidase treatment of the
      target cells abolished the GNA effect on HIV-1NDK infection. It is concluded that
      GNA inhibits infection of several HIV isolates. It neutralizes infection by
      binding to the virion but also blocks infection at the target cell level. The
      latter effect may be different for different virus isolates. Mannosyl residuals
      at the cell surface are targets for GNA modulation of infection with the
      cytopathic HIV-1NDK. These do not represent essential virus receptors.

PMID- 7734201
TI  - Activation of interleukin 4- and interleukin 6-secreting cells by HIV-specific
      synthetic peptides.
AB  - Peptides were synthesized in which the type-specific determinant of the V3 loop
      region of gp120 (SP10) was expressed C terminal to a conserved T helper epitope
      (T1) on the same molecule. These T1-SP10 peptides can stimulate both cell
      mediated and humoral immune responses. The current work used a novel approach to
      study the nature and specificity of the response elicited by these peptides.
      Cytokine-specific ELIspot assays were used to examine the number, kinetics and
      fine specificity of cells induced to secrete IL-4 and IL-6 in mice immunized with
      T1-SP10 peptides. Results indicate that the peptides activated cytokine-secreting
      cells in a dose-dependent manner in vivo. In vitro restimulation experiments
      demonstrated that both the SP10 and T1 regions contributed to this activation.
      Consistent with previous studies, mice sequentially immunized with peptides
      expressing different V3 loop regions generated B cell responses that were larger
      and more cross-reactive than those induced by a single peptide. Sequential
      immunizations had less effect on the number or specificity of the cytokine
      producing cells.

PMID- 7734202
TI  - Human nucleotide excision repair syndromes: molecular clues to unexpected
      intricacies.

PMID- 7734203
TI  - Genetic polymorphisms in xenobiotic metabolism.

PMID- 7734204
TI  - Li-Fraumeni syndrome.

PMID- 7734205
TI  - The genetics of childhood cancer.

PMID- 7734206
TI  - The genetics of colorectal cancer.

PMID- 7734207
TI  - The genetics of breast cancer.

PMID- 7734208
TI  - Multiple endocrine neoplasia type 1 (MEN1).

PMID- 7734209
TI  - Multiple endocrine neoplasia type 2.

PMID- 7734210
TI  - Neurofibromatosis type 1.

PMID- 7734211
TI  - Neurofibromatosis type 2.

PMID- 7734212
TI  - Von Hippel-Lindau disease.

PMID- 7734213
TI  - Genetic predisposition to melanoma.

PMID- 7734214
TI  - Genetics of growth arrest and cell death: key determinants of tissue homeostasis.

PMID- 7734215
TI  - Genetic counselling in the cancer family clinic.

PMID- 7734216
TI  - Screening for cancer predisposition.

PMID- 7734217
TI  - Pre-implantation diagnosis of inherited predisposition to cancer.

PMID- 7734218
TI  - Gene replacement strategies for the prevention and therapy of cancer.

PMID- 7734219
TI  - Second opinion.

PMID- 7734220
TI  - Registration and dental health benefit.

PMID- 7734221
TI  - Handpiece asepsis.

PMID- 7734222
TI  - Self-inflicted gingival injury.

PMID- 7734223
TI  - What is the future for dental specialists?

PMID- 7734224
TI  - Prevalence of complaints by patients against general dental practitioners in
      greater Manchester.
AB  - A postal questionnaire regarding potential and official patient complaints was
      sent to all dentists on the Family Health Service Authority list of four health
      districts in Greater Manchester. From an eligible sample of 335 dentists, 306
      responses were received (91%), 289 of them from general dental practitioners
      (GDPs). One hundred of the GDPs (35%) had reported at least one potential
      complaint to their defence organisation in the past 5 years (1989-1993) and 10
      GDPs had reported three or more complaints. The majority of complaints were in
      the field of restorative dentistry (57%) with complaints about oral surgery
      accounting for another 20%. Dentists who worked longer hours contacted their
      defence organisation more often regarding potential complaints. Thirty-two
      dentists reported that their most recent potential complaint had resulted in an
      official complaint being filed against them. There was a significant relationship
      between the prevalence of official complaints and the dentists' reported level of
      unsatisfactory patient visits.

PMID- 7734225
TI  - The use of sanguinarine in mouthwashes and toothpaste compared with some other
      antimicrobial agents.
AB  - Dental practitioners say that they get information to answer patients' queries on
      mouthwashes chiefly from their studies in periodontology and from articles in the
      British Dental Journal. Most practitioners who were asked about this knew of the
      benefits of Corsodyl (chlorhexidine) and fluoride-containing rinses, but few were
      aware of the active ingredients and effectiveness of the wide range of
      mouthwashes now on the market. The majority said they would welcome more
      information on this. This review was undertaken because there was a move to
      introduce mouthwashes containing sanguinarine into the UK. Part of its appeal
      would be that it is a natural therapeutic product, as distinct from a 'synthetic'
      or 'artificial' chemical. Information collected from scientific publications on
      sanguinarine, which has been in use in the USA and on the Continent in
      mouthwashes and toothpastes, is presented here. The consensus is that (a) it has
      some assets in curbing supragingival plaque, although it is uncertain whether the
      presence of zinc salts assists this, and (b) it is more effective in a mouthwash
      than in a toothpaste. It appears to be less effective than chlorhexidine, but no
      direct comparisons with triclosan preparations have been discovered. Like other
      mouthwashes, it does not affect subgingival plaque.

PMID- 7734226
TI  - An investigation into the relative efficiency of dextro-rotating and laevo
      rotating spiral paste fillers in the southern hemisphere.
AB  - Much published work evidences the differences of object-rotation which occur
      between the northern and the southern hemispheres; particularly commonly the
      evacuation of water or other liquids through a hole. This paper reports the
      results of an investigation into the efficiency with which a conventionally-wound
      clockwise-spiral root canal paste filler obturated experimentally instrumented
      root canals in the southern hemisphere as compared with those using a filler
      wound with an anticlockwise spiral.

PMID- 7734227
TI  - Periodontology: a clinical approach. 3. Non-surgical treatment and maintenance.

PMID- 7734228
TI  - Clinical decision making--an art or a science? Part VI: decision making in dental
      practice: a case study.

PMID- 7734229
TI  - Treatment of fractures and dislocations of the thoracic and lumbar spine by
      fusion and Harrington instrumentation.
AB  - Thirty-three patients with fractures of the thoracolumbar spine were treated by
      fusion and Harrington instrumentation after early reduction and stabilisation by
      postural reduction or halo-bifemoral traction. The rod-long-fuse-short technique
      was used. Postoperatively, all patients were mobilised with an external support.
      The mean follow-up was 6 years (range 1-13 years). Twenty-eight patients were
      pain-free, three patients needed sporadic pain medication. One patient was not
      working due to pain in his leg. One patient had constant pain. Twenty-three
      patients returned to work. The mean kyphosis increased from 8 degrees
      postoperatively to 13 degrees at follow-up.

PMID- 7734230
TI  - Endosteal femoral bone loss after hip rearthroplasty. A controlled computed
      tomography study of 12 patients.
AB  - The cortical bone area of the middle femur was investigated with computed
      tomography in 12 patients after hip rearthroplasty due to aseptic prosthetic
      loosening. The patients had undergone their original arthroplasty because of
      unilateral arthrosis 11 years before these measurements. Both legs were scanned,
      and the reoperated side was compared with the healthy side. A control group was
      chosen of 13 patients with unilateral hip arthroplasty because of unilateral
      arthrosis, but without subsequent rearthroplasty. In the patients who had
      undergone rearthroplasty, there was an 11% loss in endosteal bone area of the
      middle femur compared with the contralateral side. In the control group (non
      reoperated patients), only a loss of 6% was found compared with the contralateral
      side. The periosteal bone area of the reoperated femur and the non-reoperated
      femur showed no significant change compared with the corresponding healthy side.
      The larger endosteal resorption noted among patients in the rearthroplasty group
      could be ascribed to the primary prosthetic failure and could also contribute to
      further aseptic prosthetic loosening.

PMID- 7734231
TI  - Importance of lower limb surgery in Duchenne muscular dystrophy.
AB  - A total of 123 patients with Duchenne muscular dystrophy (DMD) was surgically
      treated during two different periods of their course by hip and knee release,
      aponeurectomy of the iliotibial band and z-shaped Achilles' tendon lengthening.
      In 57 patients (group I) this was carried out prophylactically as retractions of
      the lower limb joints were just beginning at the age of 6.4 +/- 1.43 years and in
      66 patients (group II) as mild contractures of the joints at the end of walking
      ability were already manifest with an average age of 9.27 +/- 1.86 years. The
      average follow-up was 3.7 +/- 1.2 years in both groups. To be able to assess the
      interindividual course of both groups, we defined "joint and motor quotients",
      which allowed a complex assessment of joint function and motoric capacity. In
      addition, both groups were compared with a control group (natural history)
      consisting of 100 non-operated DMD patients. In both groups a significant release
      of the contractures could be obtained primarily. Patients in group I showed a
      much better long-term effect than those in group II. The motor quotient in group
      I was significantly better over the whole follow-up period (P < 0.001) than in
      group II or the control group. The prolongation of walking ability by about 2
      years compared with the natural history is in our opinion not the central goal of
      this surgical treatment concept of lower limbs in DMD, but rather the
      additionally achieved prolongation of an assisted standing ability with the lower
      limbs free from contractures and deformities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734232
TI  - Mechanical and histological evaluation of hydroxyapatite-coated, titanium-coated
      and grit-blasted surfaces under weight-bearing conditions.
AB  - Cylindric titanium rods with different surfaces were axially implanted into the
      femora of sheep. The three surfaces were grit-blasted titanium, plasma-sprayed
      titanium and plasma-sprayed hydroxyapatite (HA). After 2 months, a 2-cm segment
      of the femoral shaft was completely resected to load the implant, and the animals
      were allowed full weight-bearing for 9 months. Biomechanical and histological
      evaluation of the implants was undertaken 2 months after implantation and 9
      months after the segmental resection. The mechanical testings of well-fixed
      implants were performed 9 months after segmental resection. Loosening of 45% of
      the titanium-coated implants was observed in the first 3 weeks, but thereafter,
      no further loosening occurred. The HA-coated implants remained entirely fixed for
      3 weeks, but thereafter, a progressively increasing incidence of loosening up to
      55% after 9 months of loading was detected as subsidence on X-radiographs. The
      maximum push-out strength of the titanium-coated implants was 4.9 MPa compared
      with 2.3 MPa for HA-coated ones. No significant mechanical interlock between the
      grit-blasted surface and bone was observed. The HA coating was found to be
      delaminated in all unstable implants, whereas the titanium coating remained
      completely intact. Morphometric analyses of well-fixed rods showed complete bony
      ingrowth onto the HA surface, whereas the contact area between the bone and the
      two titanium surfaces was less than 40%. Concerning clinical significance bony
      ingrowth with long-term mechanical interlock between the implant surface and the
      bone cannot be achieved by grit-blasting or HA-coating.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7734233
TI  - Glass-ceramic-coated titanium hip endoprosthesis. Experimental study in rabbits.
AB  - Titanium alloy hip endoprostheses coated with a bioactive glass ceramic (BGC)
      were followed in rabbits. All test endoprostheses remained stable, and image
      analysis showed an average of 78% bonding of the BGC-coated implants to bone at
      52 weeks. The uncoated Ti-alloy controls demonstrated an average of 37% bone
      coverage after 52 weeks. By scanning electron microscopy the thickness of the BGC
      reaction layer was found to stabilize at 60 microns after bioactive bone bonding.
      The results indicate that the BGC coating must be thicker than the reaction layer
      to prevent detachment from the core metal.

PMID- 7734234
TI  - Implant materials for hip endoprostheses: old proofs and new trends.
AB  - To judge the significance of a hip joint replacement, the clinical results over
      10-20 years must be evaluated. Today, still over half of all hip endoprostheses
      involves cement fixation. The rest is uncemented, in direct contact with bone.
      Total hip prostheses with polyethylene cups are equipped either with cobalt-,
      iron-, surface-hardened titanium-based metal or Al2O3 ceramic ball heads. The
      pairing Al2O3/Al2O3 and CoCrMoC metal/metal for cups and balls are extremely wear
      resistant. Most of the cementless cups have spherical or conical cobalt- or
      titanium-based metal shells with inserts made of polyethylene or CoCrMoC metal.
      For the fixation stems, high-strength iron-, cobalt- or titanium-based wrought
      metals are preferred. A taper spigot connection between metallic or ceramic ball
      heads and stems allows a modular design of hip joint replacements. We have learnt
      much from the mistakes of the last 40 years in hip endoprosthetics, and there is
      no excuse to repeat them again.

PMID- 7734235
TI  - Cancellous bone in human acetabulum: microradiographic and histomorphometric
      aspects.
AB  - The acetabular cancellous bone of 18 subjects aged 57-88 years was characterized
      by low mass and a poorly ramified pattern according to microradiographic
      analysis. There was no correlation between the histomorphometric data of this
      region and those of the iliac crest. Microcalluses were visible in 13 acetabular
      samples, whereas they were absent from the iliac crest. As the acetabular
      trabeculae appeared decidedly longitudinal, age-related bone rarefaction is
      suggested to occur in two different ways: uniform thinning of the trabeculae and
      selective disappearance of transverse elements. The remaining longitudinal
      trabeculae are considered to be most useful for the weight-bearing function of
      the hip joint.

PMID- 7734236
TI  - Arterial blood supply of the infrapatellar fat pad. Anatomy and clinical
      consequences.
AB  - The arterial blood supply to the infrapatellar fat pad (Hoffa's fat pad) was
      investigated in 12 knee joints of human cadavers. The infrapatellar fat pad is
      supplied by an anastomotic network which displays some striking topographic
      features. Its vascular blood supply protects it against necrosis, when either
      reconstructive operations are carried out or extensive surgical exposures of the
      knee are done. The blood supply to the center of the fat pad is limited. This is
      of practical importance for the choice of arthroscopic portals. In addition,
      arthroscopically verified sources of bleeding are described in 57 patients with
      hemarthrosis without clinically detectable instability. Rupture of the
      infrapatellar synovial fold can be a cause of posttraumatic hemarthrosis in rare
      cases. Arteries irregularly found within the fold contribute to the blood supply
      of the anterior aspect of the synovial membrane covering the cruciate ligaments.

PMID- 7734237
TI  - Biomechanical study of various greater trochanter positions.
AB  - A mathematical model was used in order to evaluate the mechanical situation after
      lateral, medial, distal and proximal displacements of the greater trochanter. It
      was calculated that lateral displacement may considerably reduce the hip joint
      contact force, while medial displacement greatly increases it. The influence of
      proximalization and distalization is much less pronounced. It was further shown
      that, regarding the postoperative relative hip abductor muscle strength, lateral
      and distal displacements of the greater trochanter are favourable, while proximal
      and medial displacements are not.

PMID- 7734238
TI  - Bipolar hemiarthroplasty in femoral neck fractures.
AB  - Thirty-two elderly patients with a femoral neck fracture treated by bipolar
      hemiarthroplasty and 36 patients (matched for age) with an Austin-Moore
      hemiarthroplasty were followed-up and compared. Bipolar replacement resulted in a
      higher percentage of satisfactory results, less postoperative pain, greater range
      of movement, more rapid return to unassisted activity, fewer unsatisfactory
      results and no acetabular erosion. The device functioned as bipolar in all the
      cases studied for inner-bearing motion.

PMID- 7734239
TI  - Macromorphological comparison of frozen sections concerning the problem of
      congruency of the hip joint.
AB  - We report on a comparative anatomical investigation of hip joints from animals
      which can walk on two legs or use their distal legs for jumping. The
      investigation supports the results of Blasius [1] that the hip is not congruent.
      The cartilage of the load induction area is thicker. This means that one can only
      see congruency on X-rays, because cartilage cannot be visualised.

PMID- 7734240
TI  - Frozen shoulder--treatment and results.
AB  - Even today the aetiology of the frozen shoulder is still under discussion. At the
      Orthopaedic Department of the Medizinische Hochschule Hannover, 118 persons with
      a frozen shoulder were treated as in- or outpatients between 1980 and 1988. We
      investigated the results of two different specific therapy concepts. Most of the
      patients received a mixture of drug therapy and physical rehabilitation under the
      guidance of a physiotherapist. In a smaller group of patients, the frozen
      shoulder was mobilized under anaesthesia (mobilisation force). After an average
      follow-up time of 3.8 years from the start of treatment, 93% of the patients was
      examined by means of an individual subjective rating (score). In addition, a
      clinical examination was performed in 69% of the cases. According to the
      subjective personal rating (score) as well as the improvement in range of motion,
      moderate mobilisation led to better results than the mobilisation under
      anaesthesia.

PMID- 7734241
TI  - Long-term follow-up of inversion trauma of the ankle.
AB  - In our institution lateral ankle ligament injuries are classified into three
      grades according to the extent of instability found on physical examination
      and/or stress X-rays. Grade I and II lesions are taped, while treatment of grade
      III lesions consists of operative reconstruction of the ruptured ligaments. In
      1989 we published the results of 1012 patients after 9 months' follow-up. About
      30% had residual complaints. The nature and frequency of the complaints were
      equally divided among the three groups. To examine the long-term follow-up
      results, we conducted a retrospective study with the same group of patients after
      6.5 years. Although ankle ligament injuries are still considered rather innocent
      lesions, we conclude that even after 6.5 years patients can still have residual
      complaints (pain, fear of giving-way, actual instability, swelling), which
      interfere with daily living and/or sport activities. The result deteriorated with
      time. This was especially prominent in the grade II group, where the percentage
      of poor and fair results doubled. The overall percentage of residual complaints
      was 39%. We conclude that there is no such thing as "a simple sprain".

PMID- 7734242
TI  - Tissue tightness disposes to disc hernia.
AB  - It seems likely that the tightness of tissue influences a patient's disposition
      to disc hernia. The aim of this study was to compare the mechanical behaviour of
      tissue from disc hernia patients with that of controls. A computerized finger
      hyperextensometer was constructed, which allowed the measurement of the
      viscoelastic properties of the capsule and ligaments at the metacarpophalangeal
      (MCP) joint. The disc group showed a reduced maximal extension angle of MCP joint
      II (P < 0.01), reduced tissue recovery value (P < 0.05), reduced relative
      subsecant area (P < 0.01) and relative integral of the regression curve (P <
      0.01). The results indicate that an anulus fibrosus with reduced extension
      properties, reduced capacity of energy absorption and retarded shape recovery
      disposes to rupture.

PMID- 7734243
TI  - Imaging the spatial distribution of membrane receptors during neutrophil
      phagocytosis.
AB  - Optical microscopy and image processing have been employed to study the
      distribution of several cell surface receptors on living human neutrophils during
      opsonin-dependent and opsonin-independent phagocytosis. Receptors were labeled
      using fluorescein-, rhodamine-, or AMCA-conjugated F(ab')2 fragments of anti-Fc
      gamma RIIIB (CD16), anti-CR3 (CD11b/CD18), and anti-uPAR (urokinase-type
      plasminogen activator receptor) antibodies, intact phycoerythrin-labeled
      interleukin 8, and fluorescein- or rhodamine-labeled Con A (concanavalin A), Boc
      PLPLP (tert-butyl-oxycarbonyl-Phe(D)-Leu-Phe(D)-Leu-Phe-OH), and N-formyl-Nle-Leu
      Phe-Nle-Tyr-Lys. Labeled neutrophils were observed during the phagocytosis of IgG
      opsonized erythrocytes and nonopsonized latex beads, Escherichia coli, and
      Staphylococcus aureus. To quantitate receptor distribution, cells were divided
      into four quadrants with the first being the point of attachment and the fourth
      being opposite the point of attachment. Ligated formyl peptide receptors, and to
      a lesser extent CR3, accumulated at the sites of target internalization for all
      forms of phagocytosis examined. However, Fc gamma RIIIB, uPAR, IL-8, Con A, and
      the FPR antagonist FBoc-PLPLP were not polarized on cells during phagocytosis.
      These data suggest that agonist-labeled formyl peptide receptors may play a
      broader role in leukocyte function than previously suggested, including possible
      participation in phagocytosis.

PMID- 7734244
TI  - Two-dimensional structure of membrane-bound annexin V at 8 A resolution.
AB  - Two-dimensional (2-D) crystals of annexin V, grown by specific binding to
      phosphatidylserine-containing planar lipid films, were studied by electron image
      analysis. Images of negatively stained two-dimensional crystals showed
      diffraction peaks extending to 11 A. After correcting lattice distorsions and
      averaging over several crystalline areas, the resolution of the analysis was
      extended up to 8 A. Observed along a direction perpendicular to the membrane
      plane, the four homologous domains characteristic of annexin V exhibit a
      noticeable difference in their distribution of protein density. An unambiguous
      assignment of the domains was possible due to the similar packing of annexin V
      molecules in the 2-D crystals and in a 3-D crystal form with pseudo-R3 symmetry.
      The domains I and IV (numbering according to Huber et al., Embo J., 1990, 9, 3867
      3874) appear well resolved. On the other hand, the two other domains, II and III,
      present an almost continuous density, with a protrusion extending outwards the
      annexin V molecule. In addition, no hydrophilic opening is resolved at the center
      of the molecule, yet a stain-filled 13-A structure is present, surrounded by
      domains I, II, and IV and distant by 5 A from the center of the molecule. We
      interpret these structural features as reflecting a conformational change in the
      annexin V structure resulting from its membrane binding.

PMID- 7734245
TI  - Direct visualization of a cardiolipin-dependent cytochrome P450scc-induced
      vesicle aggregation.
AB  - Cytochrome P450scc can be reconstituted successfully into large unilamellar
      phospholipid vesicles by a combined octylglucoside dialysis/adsorption method.
      Freeze-fracture electron microscopy was used to analyze the morphology,
      distribution, and protein topology of the cytochrome P450scc vesicles in
      dependence on lipid composition. Particles were observed only in close contact to
      the vesicle surface, probably representing tightly associated cytochrome P450scc
      at the outer vesicle surface. In cytochrome P450scc vesicles similar in lipid
      composition to the inner membrane of bovine mitochondria direct evidence by
      freeze-fracturing was found for a specific cytochrome P450scc-induced aggregation
      of the vesicles. The vesicle aggregation critically depends on the content of the
      specific mitochondrial membrane constituent cardiolipin. The aggregation and thus
      the intervesicular contacts were observed to be inhibited by both addition of
      anti-cytochrome P450scc IgG and adrenodoxin. Enzymatic reduction of cytochrome
      P450scc in the liposomal membrane by its electron transfer partners completely
      indicates an asymmetrical localization in/at the outer side of the bilayer
      membrane. It is suggested that vesiculation of the inner mitochondrial membrane
      may be a consequence of the characteristic cardiolipin-dependent cytochrome
      P450scc membrane topology: the cardiolipin binding, peripheral, non-bilayer
      spanning integration as an oligomer in the outer leaflet of the membrane may play
      a role in the dynamics of formation and dissociation of intramitochondrial
      vesicles with a functional importance for steroidogenesis.

PMID- 7734246
TI  - Centrosome behavior under the action of a mitochondrial uncoupler and the effect
      of disruption of cytoskeleton elements on the uncoupler-induced alterations.
AB  - Carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) induced in pig kidney
      embryo cells a loss of rhodamine 123 staining of mitochondria in 2-3 min. Within
      5 min after FCCP inoculation of cells prestained with rhodamine 123, the diffuse
      staining of the cytoplasm was absent. FCCP did not induce changes in the
      cytoplasmic microtubule complex, but induced nonrandom (preferentially
      perpendicular to the substrate surface) orientation of maternal centrioles.
      Nonrandom orientation of maternal centrioles occurred 10 min after treatment and
      remained for 2 hr. At 30 min after introduction of the drug, FCCP treatment
      increased the mean number of pericentriolar satellites on maternal centrioles and
      the frequency of primary cilia. The percentage of centrioles perpendicular to the
      substrate induced by FCCP treatment was slightly increased by disruption of
      microtubules and slightly diminished by disruption of microfilaments. In both
      cases centrioles were oriented significantly differently from random (P < 0.01).
      These results suggest that microtubules are neither involved in the signaling
      pathway from plasma membrane to the centriole, nor do they anchor the centrioles
      perpendicular to the substrate, as proposed by Albrecht-Buehler and Bushnell
      (Experimental Cell Research 120, 1979).

PMID- 7734247
TI  - A model of the reactive form of plasminogen activator inhibitor-1.
AB  - A model of the reactive form of plasminogen activator inhibitor-1 (PAI-1) has
      been constructed using molecular graphics and starting from the known crystal
      structure of latent PAI-1. The residues P16 to P10', of which P16-P4 form strand
      4 of the beta-sheet A (s4A) and P3-P10' form an extended loop in the latent form,
      have been removed and remodeled into this structure, based on the structures of
      ovalbumin and cleaved alpha 1-proteinase inhibitor. Residues P4'-P10' were
      remodeled as a beta-strand s1C, located on the surface of the molecule and the N
      terminal end (P16-P14) of the eliminated loop was rebuilt using appropriate
      backbone dihedrals. Subsequently, a secondary structure prediction program was
      applied and further optimization of the model was performed by several molecular
      dynamics runs. Apparently the beta-strand was stabilized by only two hydrogen
      bonds. Further analysis revealed that, although s4A was removed, s3A and s5A did
      not approach each other. In this current model it was also found that the large
      gap between the loop connecting s4C-s3C and the loop connecting s3B-hG remained
      11 A in contrast to the small gap (4A) at a similar position in other serpins.
      These observations may explain the ease of a conformational change of the
      reactive site loop of PAI-1 during transition to the latent and the preinserted
      form. In addition the current model can be used for the design of stable,
      functional, PAI-1 mutants. Detailed structural analysis of the latter may
      facilitate studies on the structure-function relationship in PAI-1 in particular
      and in other serpins in general.

PMID- 7734248
TI  - Crystallization and preliminary X-ray diffraction studies of glycine
      methyltransferase from rat liver.
AB  - Glycine methyltransferase from rat liver is a tetrameric enzyme with 292 amino
      acid residues in each identical subunit and catalyzes the AdoMet-dependent
      methylation of glycine to form sarcosine. The enzyme was crystallized by the
      hanging drop vapor diffusion method, using polyethylene glycol 4000 as a
      precipitant. The crystal belongs to the orthorhombic space group P2(1)2(1)2, with
      unit cell dimensions of a = 86.4, b = 175.7, c = 45.5 A and with two subunits in
      the asymmetric unit. The crystals diffract beyond 2.4 A resolution, and a set of
      2.4 A resolution data were measured.

PMID- 7734249
TI  - Cannabis as a medicine?

PMID- 7734250
TI  - Propofol administered by a manual infusion regimen.
AB  - We have evaluated the clinical utility and blood propofol concentrations produced
      with two different infusion regimens for propofol, given to supplement 67%
      nitrous oxide-morphine anaesthesia. Patients received a standardized three-step
      infusion of propofol based either on body weight (weight-corrected group) or on a
      mean body weight of 70 kg (standard dose group). Both groups showed similar
      cardiovascular stability and recovery times. In the 48 patients studied,
      isoflurane was used as a supplement in nine (two in the weight-corrected group).
      Apparent steady state blood propofol concentrations were 3.41 (SD 0.69)
      micrograms ml-1 in the weight-corrected group and 3.46 (0.79) microgram ml-1 in
      the standard dose group. These results suggest that for patients weighing 60-90
      kg body weight, a standard dose infusion regimen may be a suitable starting
      point. In routine clinical practice, the need for isoflurane supplementation may
      be avoided by subsequent titration of the infusion rate according to clinical
      response. Computer simulation of the actual infusion rates used in each patient
      has allowed retrospective comparison of the predictive performance of different
      pharmacokinetic descriptors for propofol. The variables described by Tackley and
      colleagues provided a more accurate prediction of the measured blood propofol
      concentration than did the variable set reported by Gepts and colleagues.

PMID- 7734251
TI  - Perioperative myocardial ischaemia in patients undergoing transurethral surgery:
      a pilot study comparing general with spinal anaesthesia.
AB  - We have studied the incidence and duration of perioperative myocardial ischaemia
      using ambulatory ECG monitoring in 100 patients undergoing transurethral surgery,
      who were allocated randomly to receive either general or spinal anaesthesia. The
      overall incidence of myocardial ischaemia increased from 18% to 26% between the
      preoperative and postoperative periods. Patients with ischaemic heart disease had
      a significantly greater incidence of myocardial ischaemia after operation than
      patients without known ischaemic heart disease (P < 0.05). There was an increase
      in both the incidence and duration of myocardial ischaemia after operation with
      both anaesthetic techniques, but no significant difference between the two.

PMID- 7734252
TI  - Hypotension during subarachnoid anaesthesia: haemodynamic effects of ephedrine.
AB  - We have compared the haemodynamic effects of ephedrine alone with ephedrine and
      colloid for the treatment of hypotension produced by subarachnoid anaesthesia in
      30 patients aged 60-90 yr with fractures of the neck of femur. Group one received
      ephedrine as an initial bolus dose of 0.2 mg kg-1 followed by an infusion of 0.5
      mg kg-1 h-1. Group two received ephedrine and colloid (polygeline, Haemaccel) 8
      ml kg-1. If necessary, up to three rescue bolus doses of ephedrine (0.1 mg kg-1)
      and then colloid solution (8 ml kg-1) were given to maintain systolic arterial
      pressure (SAP) at > 75% of baseline. Arterial pressure was measured by automated
      oscillotonometry, central venous pressure (CVP) by a manometer and cardiac index
      (CI), stroke index (SI) and heart rate (HR) by transthoracic electrical
      bioimpedance. Systemic vascular resistance index (SVRI) was derived. In patients
      receiving ephedrine only, SVRI, CVP and SI decreased and HR increased (P <
      0.0001). Five patients in this group required colloid, the effect of which was to
      restore CVP, increase CI and SI, and decrease HR (P < 0.02). In patients
      receiving ephedrine and colloid solution, SVRI decreased and CI, SI and HR
      increased (P < 0.0001). Ephedrine was not a potent arterial vasoconstrictor and
      SAP was maintained mainly by increases in SI and HR.

PMID- 7734253
TI  - Uptake of halothane and isoflurane by mother and baby during caesarean section.
AB  - Twenty-three patients undergoing Caesarean section received either 0.5% halothane
      or 0.8% isoflurane to supplement nitrous oxide-oxygen anaesthesia. We studied the
      rate of uptake of the agents by the mother and fetus by measuring partial
      pressures in maternal arterial (Pa) and fetal umbilical venous (Puv) blood. Mean
      induction-delivery interval did not differ between the halothane (10.8 min) and
      isoflurane (11.7 min) groups. There were no differences in maternal heart rate,
      arterial pressure, pH and blood-gas tensions and fetal pH, blood-gas tensions or
      Apgar scores between the two groups. Isoflurane uptake by the mother was more
      rapid than halothane; at delivery, mean Pa of isoflurane as a fraction of the
      inspired partial pressure (Pl) was 0.44 compared with 0.35 for halothane (P <
      0.05). Mean Puv as a fraction of maternal Pa at delivery was 0.71 for both
      agents; thus placental transfer was the same for both agents. Consequently mean
      Puv/Pl was greater for isoflurane (0.32) than halothane (0.26) (P < 0.05). We
      conclude that both halothane and isoflurane are suitable agents for general
      anaesthesia for Caesarean section. The rate of uptake of isoflurane by the mother
      during Caesarean section was more rapid than halothane. The rate of uptake by the
      fetus from the mother was the same for halothane and isoflurane, so that fetal
      partial pressure as a fraction of the inspired partial pressure was greater for
      isoflurane than halothane.

PMID- 7734254
TI  - Spread of subarachnoid hyperbaric amethocaine in pregnant women.
AB  - In order to examine how the gestational period influences the spread of spinal
      anaesthesia, we have measured the extent of spinal block produced by hyperbaric
      amethocaine 8 mg in 90 women. The patients were allocated to one of five groups
      according to the gestational period: non-pregnant group (n = 17), first trimester
      group (6-12 weeks, n = 14), second trimester group (13-24 weeks, n = 26), third
      trimester group (25-36 weeks, n = 15) and term group (37-41 weeks, n = 18).
      Maximum cephalad spread of analgesia was significantly higher in the second
      trimester (median T3 (range T9-C6)), third trimester (T3 (T4-C7)) and term groups
      (T2.5 (T4-C8)) than in the nonpregnant (T4 (T8-T2)) and first trimester groups
      (T4 (T11-C7)). We found that not only term pregnancy but also second and third
      trimester pregnancies enhanced the spread of spinal anaesthesia, and that first
      trimester pregnancy did not affect the spread of spinal anaesthesia.

PMID- 7734255
TI  - Effect of arm position on the effectiveness of perivascular axillary nerve block.
AB  - The influence of arm position on the effectiveness of perivascular axillary nerve
      block with a catheter was assessed prospectively in two groups of patients.
      Ninety patients were allocated randomly to receive 1% mepivacaine with adrenaline
      40 ml with the arm either adducted or abducted. Radiographs were taken in 12
      additional patients; six in each group immediately after injection of 2%
      mepivacaine 20 ml mixed with contrast agent 20 ml. There were no statistically
      significant differences in onset time, spread of analgesia, motor block or
      success rate between the two groups. Proximal flow of the local anaesthetic
      contrast agent mixture was neither facilitated by arm adduction nor was it
      necessary for the development of a successful block.

PMID- 7734256
TI  - IV compared with brachial plexus infusion of butorphanol for postoperative
      analgesia.
AB  - In a randomized, double-blind, controlled study, we have compared two groups of
      patients receiving either continuous systemic i.v. or continuous brachial plexus
      infusion of butorphanol for analgesia after operations on the upper extremities.
      Twenty-two patients undergoing elective upper extremity surgery were allocated
      randomly to one of two groups to receive either butorphanol i.v. and saline
      injected into the brachial plexus sheath (i.v. group) or butorphanol injected
      into the brachial plexus sheath and saline i.v. (brachial plexus group). After
      surgery on the upper extremity under continuous axillary brachial plexus block,
      each patient received a continuous infusion of butorphanol either i.v. or into
      the brachial plexus sheath at a dose of 83.3 micrograms h-1. Concurrently, a
      saline infusion was given via the alternate route. Patients rated their pain on a
      10-cm visual analogue scale (VAS). VAS scores in the two groups did not differ up
      to 6 h and 24 h after operation. From 9 h until 24 h after operation, pain scores
      were significantly higher in the i.v. group than in the brachial plexus group.
      The VAS score 9 h after operation was 3.3 (SD 2.7) in the i.v. group and 0.6
      (0.9) in the brachial plexus group (P < 0.01); 12 h after operation 2.7 (1.8) in
      the i.v. group and 0.6 (0.9) in the brachial plexus group (P < 0.01); 18 h after
      operation 1.7 (1.0) in the i.v. group and 0.7 (1.0) in the brachial plexus group
      (P < 0.05); and 24 h after operation 3.2 (2.4) in the i.v. group and 0.7 (1.2) in
      the brachial plexus group (P < 0.01). We conclude that continuous injection of
      butorphanol into the brachial plexus sheath provided superior analgesia compared
      with continuous i.v. injection.

PMID- 7734257
TI  - Is there any clinical advantage of increasing the pre-emptive dose of morphine or
      combining pre-incisional with postoperative morphine administration?
AB  - Pre-emptive treatment with an i.v. infusion of morphine 10 mg at induction
      reduces postoperative analgesic requirement and wound hypersensitivity compared
      with the same dose administered at the end of operation. Increasing the dose of
      preemptive morphine may potentially reduce postoperative pain further, while
      administering morphine at the end of operation, in addition to the beginning, may
      reduce pain generated by the sensory activity elicited from the wound in the
      immediate postoperative period. To examine this we have conducted a randomized,
      double-blind study in patients undergoing abdominal hysterectomy to compare the
      effect of morphine 20 mg administered before operation with 10 mg at induction
      and 10 mg on closure of the peritoneum. Postoperative pain was assessed by visual
      analogue score (VAS) at rest and on movement and by total morphine consumption
      administered by patient-controlled analgesia (PCA). Wound sensitivity was
      assessed by von Frey pain thresholds. Both groups had similar morphine
      consumption, VAS scores and touch and pain thresholds, and in both, secondary
      hyperalgesia was prevented. Nausea and vomiting scores were higher in the 20-mg
      group. There was no significant difference between the two groups and neither
      regimen appeared to offer obvious clinical advantages compared with a lower dose
      (10 mg) morphine analgesic strategy. Therefore, there may be a ceiling effect to
      the production of pre-emptive analgesia by morphine.

PMID- 7734258
TI  - Pharmacodynamics of the 1R cis-1'R cis isomer of atracurium (51W89) in health and
      chronic renal failure.
AB  - We have studied the pharmacodynamics of the 1R cis-1'R cis isomer of atracurium
      (51W89) in 15 healthy subjects and in 17 patients with chronic renal failure
      using a bolus dose of 51W89 0.1 mg kg-1 (2 x ED95). Fifteen patients with normal
      renal function were investigated also using an approximately equipotent dose of
      atracurium (0.4 mg kg-1). The compound surface action potential of the adductor
      pollicis muscle, in response to train-of-four stimulation of the ulnar nerve at
      the wrist, was recorded until recovery of the height of the first response of the
      train-of-four compared with baseline (T1:T0) had reached at least 85% and the
      train-of-four ratio (T4:T1) at least 80%. In the healthy and renal failure
      patients who received 51W89, there were no significant differences in any of the
      onset or recovery variables except for the time to 90% depression of T1:T0, which
      was longer in patients with renal failure (mean 3.7 min vs 2.4 min; P < 0.05). Of
      the healthy patients who were given either 51W89 or atracurium, there were no
      significant differences in the onset data, except for time to maximum block,
      which was longer in the 51W89 group (mean 7.7 min vs 6.2 min; P < 0.01). The mean
      times to 10%, 25%, 50% and 75% recovery of T1:T0 and the time for T4:T1 > 70%
      were significantly longer in patients receiving 51W89.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7734259
TI  - Interaction of magnesium sulphate with vecuronium-induced neuromuscular block.
AB  - We have investigated the interaction between magnesium sulphate 40 mg kg-1 i.v.
      and vecuronium. First, we determined the effect of pretreatment with magnesium on
      the potency of vecuronium using a single bolus dose-response technique. In
      addition, we compared the time course of vecuronium-induced neuromuscular block
      (vecuronium 100 micrograms kg-1) with and without magnesium pretreatment. For
      both parts, neuromuscular block was assessed by electromyography. In addition,
      the effect of magnesium pretreatment on vecuronium-induced neuromuscular block
      was investigated in the context of rapid sequence induction of anaesthesia. We
      found that the neuromuscular potency of vecuronium was increased by pretreatment
      with magnesium sulphate. The ED50 and ED90 of vecuronium with MgSO4 were 25%
      lower than without MgSO4 (ED50: 21.3 vs 26.9 micrograms kg-1; ED90: 34.2 vs 45.7
      micrograms kg-1; P < 0.05 for both). Mean onset time was 147.3 (SD 22.2) s in the
      MgSO4-vecuronium group vs 297.3 (122) s for controls (P < 0.05). Clinical
      duration was prolonged (MgSO4-vecuronium 43.3 (9) min vs 25.2 (5.1) min for
      controls; P < 0.05). This was also true for the recovery index (20.1 (6.6) min vs
      10.6 (3.4) min; P < 0.05) and duration to 75% recovery (63.4 (9.9) min vs 35.8
      (6.9) min; P < 0.05). In the context of rapid sequence induction, pretreatment
      with MgSO4 improved the intubating score of vecuronium compared with vecuronium
      without MgSO4, reaching the same quality as that with suxamethonium 1 mg kg-1. We
      conclude that magnesium pretreatment increased the neuromuscular potency of
      vecuronium, in addition to modifying the time course of its neuromuscular block.

PMID- 7734260
TI  - Antagonism of pancuronium- and pipecuronium-induced neuromuscular block.
AB  - We have compared the antagonism of neuromuscular block produced by pipecuronium
      with pancuronium in 80 anaesthetized surgical patients using mechanomyography and
      electromyography. Pancuronium 0.1 mg kg-1 or pipecuronium 0.07 mg kg-1 was given
      after induction of anaesthesia and neuromuscular block was adjusted to 75% twitch
      depression at the time of antagonism. The following regimens were used:
      edrophonium 0.5 and 1.0 mg kg-1, neostigmine 0.04 mg kg-1, pyridostigmine 0.3 mg
      kg-1 and edrophonium 0.25 mg kg-1 with pyridostigmine 0.15 mg kg-1. Antagonism
      was evaluated also by the head lift test. There was no difference between the
      reversibility of neuromuscular block produced by pancuronium or pipecuronium.
      Edrophonium produced a significantly faster antagonism than neostigmine or
      pyridostigmine but onset of action was not significantly faster than that of
      edrophonium with pyridostigmine. All regimens produced 100% (or near 100%)
      antagonism of twitch response within 15 min. However, TOF fade antagonism was
      more complete with pyridostigmine, neostigmine and edrophonium 1.0 mg kg-1 than
      with edrophonium 0.5 mg kg-1. The head lift test indicated somewhat less
      antagonism with edrophonium 0.5 and 1.0 mg kg-1. Using five monitoring methods,
      the rank order of reversal potency was: pyridostigmine approximately neostigmine
      > edrophonium 1.0 mg kg-1 > edrophonium+pyridostigmine > edrophonium 0.5 mg kg-1.

PMID- 7734261
TI  - Prevention of hypothermia during orthotopic liver transplantation: comparison of
      three different intraoperative warming methods.
AB  - Hypothermia is a frequent and sometimes clinically important problem during
      orthotopic liver transplantation. Numerous methods have been suggested to reduce
      intraoperative heat loss and promote active warming. In this study we compared an
      electric under mattress, a warm air under mattress and a forced warm air
      convective heating blanket. The forced air convective warming system was shown to
      produce significantly higher patient temperatures than the two other systems.

PMID- 7734262
TI  - Comparison of the haemodynamic effects of dopamine and dobutamine in young
      children undergoing cardiac surgery.
AB  - Nineteen children, aged 2-54 months, requiring high-dose inotropic support after
      cardiac surgery, were given either dopamine or dobutamine in a blinded, double
      crossover, study. Using a pulmonary artery thermistor, right and left atrial
      cannulae, and pulmonary and femoral arterial catheters, conventional haemodynamic
      variables were measured hourly over three consecutive 4 h dopamine-dobutamine
      dopamine or dobutamine-dopamine-dobutamine exchanges. No significant differences
      in haemodynamics occurred during dopamine therapy compared with the same dose of
      dobutamine in 14 patients receiving phenoxybenzamine 2 mg kg-1, four of whom had
      also received enoximone. In five patients, neither enoximone nor phenoxybenzamine
      was used and significant increases in pulmonary artery pressure and pulmonary
      vascular resistance (P = 0.04) occurred when patients were given dopamine rather
      than dobutamine. We conclude that dobutamine and dopamine are equipotent
      inotropes in children and that dopamine in doses > 7 micrograms kg-1 min-1,
      caused pulmonary vasoconstriction, an effect mediated by alpha adrenergic
      receptors.

PMID- 7734263
TI  - Cardiovascular consequences of severe hypophosphataemia in brain-dead patients.
AB  - Hypophosphataemia is known to induce reversible myocardial dysfunction, but the
      incidence of hypophosphataemia and its effect on myocardial function during brain
      death are unknown. In 90 consecutive brain-dead patients, we measured plasma
      concentrations of phosphate and left ventricular ejection fraction area (LVEFa),
      using transoesophageal echocardiography. In 15 severely hypophosphataemic (< 0.40
      mmol litre-1), consecutive, brain-dead patients, haemodynamic status, LVEFa, and
      oxygen delivery and consumption were assessed before and after phosphorus loading
      (0.30 mmol kg-1). In 10 other brain-dead patients, urine elimination of
      phosphates was measured. Only 30 (33%) brain-dead patients had normal plasma
      phosphate concentrations, 22 (24%) had mild hypophosphataemia (0.40-0.80 mmol
      litre-1) and 38 (42%) had severe hypophosphataemia (< 0.40 mmol litre-1). There
      were no significant differences in LVEFa between these three groups (mean 53 (SD
      16), 55 (12) and 51 (17)%, respectively) and no significant correlation between
      LVEFa and plasma phosphate concentration (r = 0.04). In 15 severely
      hypophosphataemic patients, phosphorus loading increased plasma phosphate
      concentration from 0.30 (0.10) to 1.06 (0.41) mmol litre-1, but did not modify
      haemodynamic status, LVEFa or oxygen delivery and consumption. In 10 other
      patients, urine phosphorus elimination was 16.8 (23.3) mmol/24 h while plasma
      phosphate concentration was at its highest level (0.80 (0.37) mmol litre-1), and
      only one of these patient had a slightly elevated phosphaturia. In conclusion,
      hypophosphataemia frequently occurs after brain death but has no significant
      cardiovascular consequences, suggesting that it is related to intracellular
      transfer and not phosphorus depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734264
TI  - Radioimmunoassay for plasma histamine: a study of false positive and false
      negative values.
AB  - In order to achieve a correct diagnosis of drug anaphylaxis using a
      radioimmunoassay devoid of interferences, we have studied factors leading to
      false positive or false negative values of plasma histamine. Different steps in
      sample collection were studied systematically in 30 normal volunteers. False
      positive values were found in haemolysed samples, with histamine concentrations
      being correlated with haemoglobin concentrations, and where plasma was aspirated
      from the white-cell layer. There was no significant increase when a tourniquet or
      vacuum tubes were used, or when blood tubes were left at 4 degrees C overnight.
      In 12 patients who experienced an anaphylactic reaction, histamine disappeared
      from blood 10 times more slowly than expected. False negative values were found
      in two pregnant women and one heparinized patient. Histamine was remarkably
      stable in vitro in blood or plasma samples, whereas it disappeared rapidly when
      plasma from a pregnant woman or a heparinized patient was added to the sample. We
      conclude that false positive and false negative values are rare when using this
      radioimmunoassay.

PMID- 7734265
TI  - Effects of phenylephrine and prostaglandin E1 on ventriculo-arterial matching
      during halothane anaesthesia.
AB  - We have investigated the effects of phenylephrine alone and combined with
      prostaglandin E1 (PGE1) on ventriculo-arterial matching during halothane
      anaesthesia in dogs. The ratio of left ventricular end-systolic elastance (Ees)
      to effective arterial elastance (Ea) was used as an index of ventriculo-arterial
      matching. In group 1 (n = 7), measurements were performed at control, 1.5%
      halothane, halothane+phenylephrine 1-10 micrograms kg-1 min-1, and
      halothane+phenylephrine+PGE1 0.2-1.0 or 1.0-2.0 micrograms kg-1 min-1. In group 2
      (n = 5), dobutamine 2 and 5 micrograms kg-1 min-1 was infused during halothane
      anaesthesia. Halothane 1.5% decreased mean arterial pressure (MAP), cardiac
      output and Ees. Phenylephrine restored MAP, but further decreased cardiac output.
      The decrease in Ees produced by halothane was reversed by phenylephrine. PGE1
      increased cardiac output and reversed the increases in Ea and Ea/Ees during
      phenylephrine infusion. Dobutamine also reversed halothane-induced decreases in
      MAP, cardiac output and Ees, and improved Ea/Ees. Our results indicate that
      combined use of PGE1 with phenylephrine can eliminate the vasoconstrictive
      property of phenylephrine, resulting in an improvement in ventriculo-arterial
      matching.

PMID- 7734266
TI  - Nitric oxide: an endogenous gas.

PMID- 7734267
TI  - Effect of renal function on neuromuscular block induced by continuous infusion of
      mivacurium.
AB  - We have studied the effect of renal function on the pharmacodynamics of
      mivacurium. Sixty patients were allocated to three groups according to creatinine
      clearance: group C (control), creatinine clearance > 50 ml min-1; group P
      (preterminal renal failure), creatinine clearance < 50 ml min-1 > 20 ml min-1;
      group T(terminal renal failure), creatinine clearance < 20 ml min-1.
      Neuromuscular transmission (train-of-four) was monitored using electromyography
      from the hypothenar muscle with stimulation of the ulnar nerve. After an initial
      bolus, mivacurium was administered continuously to maintain a T1 of 5 (4)% of
      baseline. The dose of mivacurium necessary to maintain 95% neuromuscular block
      was similar in patients with normal renal function and patients with different
      levels of renal impairment. Recovery from neuromuscular block after ceasing
      mivacurium infusion was significantly prolonged in patients with preterminal
      renal impairment. There was a close correlation between mivacurium
      pharmacodynamics and pseudocholinesterase activity, but not creatinine clearance.

PMID- 7734268
TI  - Dexmedetomidine does not modify the neuromuscular blocking action of vecuronium
      in the anaesthetized rat.
AB  - Dexmedetomidine is a new alpha 2 adrenergic agonist anaesthetic adjuvant. In
      animal studies, dexmedetomidine produced muscle flaccidity and prevented opioid
      induced muscle rigidity, apparently via a central mechanism. The effect of
      dexmedetomidine on the neuromuscular junction or on non-depolarizing
      neuromuscular block during anaesthesia has not been reported. We have studied in
      the anaesthesized rat, the effects of dexmedetomidine on vecuronium-induced
      twitch depression. Wistar rats (n = 35) were anaesthetized and their lungs
      ventilated to maintain normocapnia. An infusion of vecuronium of 2.3 (SEM 0.1)
      micrograms kg-1 min-1 produced a stable twitch height (T1) depression of the
      tibial nerve of 53 (2)% of control in all groups. Rats were allocated randomly to
      receive either saline or dexmedetomidine 10, 30 or 100 micrograms kg-1 i.v. and
      T1 height was measured continuously for 60 min. Dexmedetomidine did not
      significantly affect T1 height during the first 30 min of infusion. At later
      times there were minor differences between groups. With cessation of the infusion
      of vecuronium, T1 height recovered rapidly to normal in all groups. These data
      suggest that the neuromuscular blocking properties of dexmedetomidine are
      unlikely to be produced by action at the neuromuscular junction.

PMID- 7734269
TI  - Extradural ropivacaine and bupivacaine in hip surgery.
AB  - We studied 126 patients undergoing elective hip surgery; they received 20 ml of
      0.5%, 0.75%, 1.0% ropivacaine or 0.5% bupivacaine extradurally in a double-blind
      design. Sensory block (pinprick), motor block (modified Bromage scale), quality
      of analgesia and neuromuscular block were assessed intermittently. Heart rate and
      arterial pressure were measured at regular intervals. A total of 115 patients
      were evaluated for efficacy. Onset of analgesia, onset of motor block and maximum
      cephalad spread (T4) did not differ between the groups. Duration and quality of
      analgesia and motor block increased with the concentration of ropivacaine.
      Ropivacaine 1.0% provided a longer duration of analgesia and motor block, more
      intense motor block and more patients with satisfactory analgesia than 0.5%
      bupivacaine. More patients treated with the higher concentrations of ropivacaine
      required treatment for hypotension and bradycardia.

PMID- 7734270
TI  - Right upper lobectomy in a patient with an iatrogenic tracheo-oesophageal fistula
      after laryngectomy.
AB  - A patient with a tracheostomy and an iatrogenic tracheo-oesophageal fistula
      presented for diagnostic bronchoscopy and right upper lobectomy. The anaesthetic
      management is discussed with reference to the options available and, in
      particular, the use of a Brompton Pallister single lumen endobronchial tube.

PMID- 7734271
TI  - Prolonged postoperative analgesia for arthrolysis of the elbow joint.
AB  - We describe the provision of postoperative analgesia for 6 days for a patient
      undergoing arthrolysis of the elbow joint. Mobilization of the elbow immediately
      after operation is essential to maintain movement achieved with surgery and this
      can be obtained only with effective pain relief. We used continuous infusion of
      0.125% bupivacaine and subsequent addition of fentanyl to the infusate, via a
      catheter inserted supraclavicularly into the sheath of the brachial plexus.

PMID- 7734272
TI  - Reflux during positive pressure ventilation via the laryngeal mask airway?

PMID- 7734273
TI  - Prediction of difficult tracheal intubation.

PMID- 7734274
TI  - Heparin and platelet function.

PMID- 7734275
TI  - Effects of oral nizatidine on preoperative gastric fluid pH and volume in
      children.

PMID- 7734276
TI  - Viscosities of commonly infused substances.

PMID- 7734277
TI  - Neuromuscular block and tourniquets.

PMID- 7734278
TI  - Effects of extradural sufentanil and morphine on ventilation.

PMID- 7734279
TI  - VII International Symposium on Magnesium. Lisbon, Portugal, 4-9 October 1994.
      Abstracts.

PMID- 7734280
TI  - Expanded programme on immunization. Immunization of adults against diphtheria.

PMID- 7734281
TI  - In memoriam Margaret Hay Edwards, MD, MPH.

PMID- 7734282
TI  - A prospective view of the EACE. European Association for Cancer Education.

PMID- 7734283
TI  - Clinical trials and practice guidelines as educational methods in developing
      countries.

PMID- 7734284
TI  - Cancer education in Viet Nam.

PMID- 7734285
TI  - Educational characteristics of tumor conferences in teaching and non-teaching
      hospitals.
AB  - Hospital tumor conferences (tumor boards) were observed and evaluated over an 18
      month period to determine their organizational and educational characteristics as
      well as their impact on conference participants. In conjunction with a previous
      nationwide survey of tumor conferences, this study was designed to identify
      features that would facilitate the learning that occurs in conference sessions.
      Study investigators observed a regional sample of 43 tumor boards in 37
      participating hospitals, which included 513 sessions at general (hospital-wide)
      conferences and 198 sessions at specialty conferences. A total of 1,866 tumor
      cases were presented during these 711 conferences. Participants completed
      questionnaires to supplement the investigators' evaluations. Session observations
      revealed several ways in which tumor boards could increase their educational
      impact on participants, including combining case presentations with presentations
      of related didactic material and using the method of progressive disclosure to
      promote increased participation in discussions related to retrospective case
      presentations. Improvements can be made in session organization and case
      presentation with the potential for increasing participant learning with little
      increase in the effort or expense associated with tumor conferences.

PMID- 7734286
TI  - Educational and consultative functions, topics, and methods of hospital general
      tumor conferences.
AB  - The educational and consultative functions, topics, and methods of 20 hospital
      general tumor conferences in Colorado were studied over a three-year period.
      Methods used included questionnaires completed by hospital admitting staff
      members, by tumor conference directors, and by conference attendees. Workshops
      were held in which a multidisciplinary panel of physicians, nurses, and cancer
      registrars discussed the educational and patient-management aspects of tumor
      conferences with tumor conference directors. The study design included evaluation
      of the effects of providing certain teaching aids, including newsletters,
      Physician Data Query printouts, and tumor registry data on the functions, topics,
      and methods of the conferences. Although certain temporal trends were suggested,
      the handouts as employed added little of perceived effectiveness for the busy
      clinicians attending. The characteristics of the tumor conferences were analyzed
      according to hospital size, presence of one or more residency programs, and
      location (metropolitan or otherwise). One observation was that relatively few
      primary care physicians attended these tumor conferences, especially those in
      large hospitals, and approaches to meeting the needs of that group are discussed.
      The importance of the interpersonal skills of the tumor conference director in
      the effectiveness of the conference was very evident.

PMID- 7734287
TI  - Postgraduate training program for the diagnosis and follow-up of cancer:
      experience of the University of Oviedo, Spain.
AB  - In anticipation of the expected worldwide increase in cancer deaths, the
      University of Oviedo in 1987 launched a two-year-long doctorate program entitled
      "Training Programme for the Diagnosis and Follow up of Cancer." The course was
      organized in three modules, General Basis, Methods, and Applications. Doctoral
      candidates acquired experience in these areas by means of theoretical lessons,
      practical work, and seminars with required preparation of special projects. From
      1987 to 1990, 30 doctoral candidates completed the program. Some developed
      impressive projects and doctoral theses on aspects of cancer in the course of the
      program, which was offered twice, in 1987-88 and in 1988-89.

PMID- 7734288
TI  - Housestaff training in cancer pain education.
AB  - A program for improving housestaff education in cancer pain control was piloted
      on an inpatient oncology unit during academic year 1992-93. Housestaff (four or
      five first-year residents and two more senior residents per month) received a
      three-day lecture series each month. A total of 32 housestaff participated. A
      questionnaire (Test A) about cancer pain was administered before the series. The
      subjects scored 58% correct (range 49-69). When Test A was repeated at the end of
      each rotation, the subjects scored 83% correct (range 82-86, p < 0.0001). A quiz
      on analgesic dosing (Test B) was also administered. The subjects scored 38%
      (range 20-56) before the lectures, 81% (range 72-93) immediately after the
      lectures, and 57% (range 44-67) at the end of the rotation. The authors conclude
      that this pilot project improves knowledge about cancer pain, but sustained
      reinforcement is needed if analgesic dosing skills are to be maintained.

PMID- 7734289
TI  - Development of a cervical cancer education program for native American women in
      North Carolina.
AB  - The North Carolina Native American Cervical Cancer Prevention Project is a five
      year, NCI-funded public health education program. The project was developed to
      address the problem of excess mortality from cervical cancer among Native
      American women by increasing screening and follow-up of abnormal cervical smears.
      This paper describes the process of developing and implementing the intervention,
      an individualized health education program. Development of the intervention was
      guided by the health belief model, social learning theory, self efficacy theory,
      and PRECEDE, a planning model. Community analysis revealed that the target
      populations had limited awareness of cervical cancer as a specific type of
      cancer, and had an experientially-based pessimistic outlook regarding survival
      with cancer. Steps in developing the cervical-cancer prevention program included
      1) development of objectives, 2) selection of strategies and development of
      cervical cancer education materials, 3) pretesting and revision, and 4)
      implementation, monitoring, and further revision. Native American lay health
      educators were recruited and trained to deliver the program. The experience of
      developing and implementing the individualized health education program suggests
      that the design of health education programs for Native Americans should begin
      with examination of basic assumptions regarding the nature of health and illness
      in the target population. The unique cultures and the diversity of Native
      American populations are critical factors in the development of health education
      programs for them.

PMID- 7734290
TI  - Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell
      lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well
      established clinicopathological parameters which have unfortunately become
      insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl
      2 gene deregulations are frequently involved in several types of epithelial
      malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101
      cases of NSCLC respectively. The expression was then compared with established
      indicators of prognosis and biological behaviour of the tumours. No relationship
      was observed between Bcl-2 and either clinicopathological or biological
      parameters such as histology, grading, tumour status, nodal metastasis and
      proliferative activity evaluated by scoring proliferating cell nuclear antigen
      expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was
      significantly lower in patients who developed metastasis during follow-up or died
      of metastatic disease (P = 0.006 and P = 0.01 respectively). Moreover, survival
      probability was higher in patients who expressed the Bcl-2 protein (P = 0.0002).
      In contrast with this, p53 protein accumulation was observed in tumours with
      metastatic nodal involvement (P = 0.02) or in patients who developed metastasis
      during follow-up (P = 0.01), although no correlation was found between p53
      expression and overall survival. An inverse relationship was also found between
      Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high
      proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have
      prognostic importance.

PMID- 7734291
TI  - p53 oncoprotein overexpression correlates with mutagen-induced chromosome
      fragility in head and neck cancer patients with multiple malignancies.
AB  - In this study, we analysed immunocytochemically p53 expression in first primary
      and second primary cancers from 25 head and neck cancer patients (HNCPs) with
      multiple malignancies in comparison with oncoprotein expression in tumour tissues
      from 25 historical HNCP controls with single cancer in a match-paired analysis.
      Moreover, we investigated bleomycin-induced chromosome fragility in both groups
      of HNCPs and in 21 additional healthy controls. Thirty-nine out of 75 tumour
      specimens analysed (52%) showed positive p53 immunostaining. Eleven out of 25
      (44%) from single cancer patients and 28 out of 50 (56%) tumours from HNCPs with
      multiple malignancies were p53 positive. In the group of multiple primary
      cancers, nine patients (36%) showed positive staining of both first and second
      primaries, whereas six (24%) had positive labelling of first primary cancer but
      not of the subsequent second primary, four (16%) patient showed p53 expression
      only in the second primary cancer and six (24%) patients showed no p53
      immunoreactivity in both tumours. Chromosomal analysis demonstrated a higher
      sensitivity to clastogens of HNCPs with multiple tumours than of HNCPs with a
      single cancer (P < 0.01), and a significant correlation between chromosome
      fragility and p53 overexpression (P < 0.01) only in HNCPs with multiple
      malignancies more than in those with single head and neck cancer (P = 0.11).
      Moreover, we found that patients with p53-positive staining of both first and
      second primaries showed a statistically significant higher mutagen sensitivity
      than those with a single p53 immunoreactive tumour or those in whom both cancers
      were p53 negative (P < 0.01). Our data suggest that subjects with increased
      susceptibility to carcingogens after exposure to tobacco or alcohol are at higher
      risk for multiple cancers in which one of the most common genetic events is
      aberrant p53 expression.

PMID- 7734292
TI  - Prognostic significance of p53 overexpression in primary breast cancer; a novel
      luminometric immunoassay applicable on steroid receptor cytosols.
AB  - A novel quantitative luminometric immunoassay (LIA) has been developed for the
      measurement of wild-type and mutant p53 protein in extracts from breast tumour
      tissue. The LIA was found to yield reliable estimates of p53 expression in
      cytosol samples routinely prepared for steroid receptor analysis as compared with
      results obtained with immunohistochemical analysis. The LIA was evaluated on 205
      primary breast tumour cytosols prepared for steroid receptor analysis and stored
      frozen at -80 degrees C for 6-8 years, p53 protein being detected in 65% of the
      samples (range 0.01-23 ng mg-1 protein). Using an arbitrary cut-off value of 0.15
      ng mg-1 protein, 30% of the tumours were classified as manifesting p53
      overexpression. Significant and independent correlations were found to exist
      between p53 overexpression and shorter disease-free (P < 0.001) and overall
      survival (P = 0.039) at a median duration of follow-up of 50 months. p53
      overexpression was related to low oestrogen receptor content and high
      proliferation rate (S-phase fraction). No relationship was found to tumour size
      or the presence of lymph node metastasis. Three tumours possessed an extremely
      high p53 content (> 10 ng mg-1 protein), all of which were of medullary or high
      grade ductal type, oestrogen and progesterone receptor negative, DNA non-diploid,
      had S-phase fractions of > 22% and recurred within 1-2 years. In summary, a new
      sensitive and quantitative LIA suitable for routine analysis of p53 protein in
      steroid receptor cytosol preparations from breast tumours has been developed to
      confirm the prognostic importance of p53 protein accumulation in human breast
      cancer.

PMID- 7734293
TI  - Nuclear proto-oncogene products transactivate the human papillomavirus type 16
      promoter.
AB  - Human papillomavirus (HPV) type 16 and 18 viral genomes are frequently detected
      in cervical and penile cancer biopsies. Although this strongly suggests a
      prominent role for HPV infection in the development of genital cancer, other
      genetic or environmental factors are also involved. Genital cancer is postulated
      to result from loss of cellular control functions, which leads to an unregulated
      expression of HPV oncogenic proteins. In our study, we determined the trans
      activating properties of nuclear proto-oncogene proteins c-Fos, c-Jun and c-Myc
      on P97 enhancer/promoter activity of HPV16. Using a CAT-reporter construct
      containing the HPV16 enhancer/promoter element, we investigated the trans
      activating effects of c-Fos, c-Jun, c-Myc, and E2 in cervical HT-3 cells. c-Fos
      and c-Jun overexpression resulted in a 3.3- and 3.1-fold up-regulation of CAT
      activity. Only 2-fold induction was determined by co-transfection with c-myc and
      the viral transcription factor E2. Based on these findings, we investigated the
      expression of HPV DNA (16 and 18) as well as nuclear proto-oncogenes (c-fos, c
      jun and c-myc) in nine cervical cancers by in situ hybridisation. In six out of
      nine carcinomas, HPV16 and/or HPV18 DNA was detectable. All tumours showed an
      intense and homogeneous expression of c-fos and c-jun mRNA, while the signal for
      c-myc was detectable only in four specimens. These data suggest that deregulation
      of nuclear proto-oncogene expression may contribute to an overexpression of HPV
      derived oncogenic proteins (E6 and E7), which is generally hypothesised to be an
      important step in the malignant transformation of HPV-associated tumours.

PMID- 7734294
TI  - Assay of matrix metalloproteases types 8 and 9 by ELISA in human breast cancer.
AB  - Results from model tumour systems suggest that either increased levels of certain
      metalloproteases (MMPs) or decreased levels of their inhibitors correlate with
      metastatic potential. In this study, levels of two MMPs, i.e. MMP-8 and -9, and
      their inhibitor tissue inhibitor of metalloprotease type 1 (TIMP-1) were measured
      by enzyme-linked immunosorbent assay in human breast tumours. Levels of MMP-8 and
      -9 correlated significantly with each other, but neither MMP correlated with
      urokinase plasminogen activator. Levels of both MMP-8 and -9 were also
      significantly related to levels of TIMP-1. In contrast, neither MMP correlated
      with plasminogen activator inhibitor. No relationship was found between MMP-8,
      MMP-9 or TIMP-1 and either tumour size or metastasis to axillary nodes. MMP-8 and
      -9 levels were inversely related to levels of oestrogen receptors. MMP-8 but not
      MMP-9 levels were also inversely correlated with progesterone receptor levels. It
      is concluded that the assay for MMP-8 and -9 described here will permit the
      evaluation of these proteases as prognostic markers in cancer.

PMID- 7734295
TI  - Do DNA ploidy and S-phase fraction in primary tumour predict the response to
      chemotherapy in metastatic breast cancer?
AB  - The relationship between the response to chemotherapy with cyclophosphamide,
      epirubicin and fluorouracil as well as the time to progression of metastasised
      breast cancer and DNA ploidy and S-phase fraction (SPF) of primary tumours was
      examined using paraffin-embedded tumour tissue from 81 patients. The response to
      chemotherapy was significantly better in patients with tumours with a high SPF,
      and in addition the time to progression was longer in the high-SPF group. There
      was no significant difference when the DNA ploidy and response to treatment were
      compared.

PMID- 7734297
TI  - Inhibin as a marker for ovarian cancer.
AB  - Inhibin is a polypeptide hormone produced by the granulosa cells of the ovary,
      and is present in body fluids as dimers of various sizes each comprising an alpha
      and beta-subunit. Free forms of the alpha-subunit also circulate, and the
      presently available radioimmunoassay (Monash assay) cannot distinguish these from
      biologically active dimeric inhibin. Recently we described a new two-site enzyme
      immunoassay able for the first time to measure the levels of dimeric inhibin
      throughout the human menstrual cycle. The sensitivity limit of this assay is 2 pg
      ml-1 in human serum with cross-reactivity against activin of 0.05%. The normal
      range of inhibin in post-menopausal women is < 5 pg ml-1, in pre-menopausal women
      2-80 pg ml-1 (2-10 pg ml-1 in the follicular phase, 40-80 pg ml-1 in the luteal
      phase). This assay was used to determine inhibin levels in sera from 15 (five pre
      menopausal and ten post-menopausal) patients with granulosa cell tumours of the
      ovary. It was raised in a pre-menopausal patient preoperatively (261 pg ml-1), in
      six post-menopausal patients (32, 43, 54, 66, 24 and 58 pg ml-1) and one pre
      menopausal patient with recurrent tumour, (237 pg ml-1), all confirmed
      clinically. Inhibin was normal in six patients in remission. Oestradiol levels
      were normal in all patients. Serial levels of inhibin predicted recurrence before
      overt clinical relapse in two patients. In 29 patients with malignant epithelial
      ovarian tumours inhibin levels were modestly elevated in nine and normal in the
      rest. Three patients with endometrioid histology, two with undifferentiated
      tumours, three with mucinous adenocarcinoma and one with clear cell carcinoma had
      elevated inhibin levels. Functional inhibin is secreted by all granulosa cell
      tumours of the ovary studied and can be used as a tumour marker to determine
      response to therapy and predict recurrence and is superior to oestradiol. A more
      detailed analysis of the levels of inhibin, and its subunits in epithelial
      ovarian cancer is needed to identify the molecular forms of the immunoreactive
      material before optimised assays can be applied to this more common tumour.

PMID- 7734298
TI  - TATI (tumour-associated trypsin inhibitor) as a marker of ovarian cancer.
AB  - In ovarian cancer patients a 6 kDa polypeptide, the tumour-associated trypsin
      inhibitor (TATI), can occur at elevated concentrations in both urine and serum.
      In this study pretreatment serum levels of TATI (cut-off point 21 ng ml-1) and CA
      125 (cut-off points 35 U ml-1 and 65 U ml-1) were determined in 152 patients with
      epithelial ovarian cancer (115 primary and 37 recurrent) and in 267 women with
      benign pelvic diseases. The data obtained were correlated with the tumor stage,
      histological type and tumour grade. Overall, TATI showed a sensitivity of 64% and
      a specificity of 75%. The sensitivity and specificity of CA 125 > 35 U ml-1 were
      both 80%. Corresponding values for CA 125 > 65 U ml-1 were 70% and 87%. The
      combination of the two markers increased the sensitivity to 91% (CA 125 > 35 U ml
      1) and 86% (CA 125 > 65 U ml-1), while the specificity dropped to 61% and 68%
      respectively. TATI was clearly superior in mucinous carcinomas of the ovary, the
      rate of true-positive findings in these neoplasms was 67% vs 42% for CA 125 > 35
      U ml-1 and 33% for CA 125 > 65 U ml-1. Unlike CA 125, TATI correlated well with
      tumour grade. The combination of the two markers had a higher negative predictive
      value, i.e. 93% (CA 125 > 35 U ml-1) and 90% (CA 125 > 65 U ml-1) respectively.
      It is concluded that, while TATI cannot replace CA 125 in the diagnosis of
      malignant epithelial carcinomas of the ovaries, it is a valuable additional
      marker in cases of mucinous carcinomas and in combination with CA 125.

PMID- 7734296
TI  - Co-culture of human breast adenocarcinoma MCF-7 cells and human dermal
      fibroblasts enhances the production of matrix metalloproteinases 1, 2 and 3 in
      fibroblasts.
AB  - No measurable amounts of matrix metalloproteinases (MMPs) were produced by human
      breast adenocarcinoma cell lines MCF-7 and BT-20 in culture. When MCF-7 cells
      were co-cultured with human dermal fibroblasts enhanced production of precursors
      of MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1)
      and tissue inhibitor of metalloproteinase type 1 (TIMP-1) was observed.
      Immunohistochemical studies indicated that these pro-MMPs originated primarily
      from the fibroblasts, suggesting that MCF-7 cells have a stimulatory effect on
      stromal cells to produce at least three pro-MMPs and TIMP-1. BT-20 cells also
      enhanced the production of pro-MMP-2 and TIMP-1 in the dermal fibroblasts, but
      not of pro-MMP-1 and pro-MMP-3. Normal mammary epithelial cells promoted only
      TIMP-1 production. To investigate further the stimulatory factors from MCF-7
      cells, the conditioned medium and the cell membrane were prepared and examined.
      The cell membrane fraction enhanced the production of pro-MMP-1 and -3 and TIMP
      1, but not of pro-MMP-2. The conditioned medium, on the other hand, augmented the
      production of all four proteins in the fibroblasts. These observations suggest
      that breast adenocarcinoma MCF-7 cells in culture produce both soluble and
      membrane-bound factor(s) which stimulate the production of pro-MMPs and TIMP-1 in
      neighbouring stromal cells, but the factor(s) released into the medium and that
      associated with cell membranes are probably different. Such communication between
      the normal and malignant cell types may, in part, assist the cancer cells to
      invade and metastasise.

PMID- 7734299
TI  - Histopathological grading and DNA ploidy as prognostic markers in metastatic
      prostatic cancer.
AB  - The present study compares the prognostic potential of tumour grade and DNA
      ploidy status in patients with advanced-stage prostatic cancer. Two outcome
      groups were selected on the basis of time to progression and survival after
      orchiectomy. A poor-outcome group consisted of 32 therapy-resistant patients who
      experienced disease progression during the first year after orchiectomy and
      subsequently death due to prostatic cancer during the following year. A good
      outcome group consisted of 27 therapy-responsive patients who showed disease
      regression and no signs of progression during a 3 year follow-up. The primary
      tumours were graded twice according to WHO and Gleason classification systems by
      two pathologists. Final agreement between the pathologists was obtained after a
      consensus meeting. The analysis revealed no prognostic importance of the two
      histological classification systems (P = 0.62 and P = 0.70) and disclosed weak
      inter- and intra-observer reproducibility (kappa < 0.70). DNA ploidy analyses
      were performed by image cytometry on formalin-fixed, paraffin-embedded samples of
      the primary tumours. Overall, 48% of the tumours were diploid, 20% tetraploid and
      32% anueploid. DNA ploidy status did not discriminate between the two outcome
      groups (P = 0.46). Histological grade and DNA ploidy showed no prognostic
      importance in patients with prostatic cancer and skeletal metastases.

PMID- 7734300
TI  - Type I collagen degradation product (ICTP) gives information about the nature of
      bone metastases and has prognostic value in prostate cancer.
AB  - Although osteosclerotic bone metastases are characteristic of prostate cancer,
      mixed metastases with a lytic component are not uncommon. Type I collagen is
      synthesised by osteoblasts and accounts for about 90% of the organic matrix of
      bone. We have used new specific immunoassays for PICP (carboxy-terminal
      propeptide of type I procollagen) and ICTP (cross-linked carboxy-terminal
      telopeptide of type I collagen) which allow simultaneous assessment of the
      synthesis and degradation of type I collagen respectively. Forty patients with
      bone metastases due to prostate cancer at the time of diagnosis were investigated
      with these methods. Twenty-three of them had sclerotic (S) and 17 had mixed
      metastases with sclerotic and lytic components (S + L) as assessed by
      radiographs. The concentrations of PICP and ICTP in serum as well as the activity
      of alkaline phosphatase (AP) were increased in all patients of the S + L group,
      who had more aggressive bone disease and a shorter survival than the S group (P <
      0.017). The ICTP level was above the reference range in half of the patients in
      the S group, whereas the PICP and AP levels were elevated in 35%. Of the bone
      markers, only ICTP was of prognostic significance (P < .05). We conclude that
      ICTP and PICP give information about the type and activity of the skeletal
      metastases. In addition, ICTP predicts prognosis.

PMID- 7734301
TI  - Microsatellite instability in squamous cell carcinoma of the head and neck.
AB  - Genomic instability or microsatellite instability (MI) in simple repeated
      sequences was initially recognised in colonic carcinomas and subsequently in
      other tumours. MI has been associated with mutations in genes concerned with
      replication and DNA repair. We investigated 34 microsatellite markers in squamous
      cell carcinoma of the head and neck (SCCHN). Fifty-six tumours, were studied, of
      which 25 were investigated with ten or more microsatellite markers. In this study
      we consider two or more microsatellite alterations in a tumour to be diagnostic
      of MI. We demonstrated that 7/25 (28%) of the tumours had MI at two or more loci
      and three of these tumours exhibited evidence of 20 or more loci with MI. No
      correlations were found between MI and previous treatment, site, histological
      differentiation, positive nodes at pathology, a history of alcohol intake or
      survival. MI has been demonstrated in T1N0 stage tumours, indicating that these
      changes may occur early in the disease process. A negative correlation was found
      between MI and a history of smoking (P = 0.02). Two or more markers of MI were
      found in three of four non-smokers compared with one of 13 in the smoking group
      of patients, which suggests a novel mechanism of carcinogenesis in non-smokers.

PMID- 7734302
TI  - Colorectal carcinomas show frequent allelic loss on the long arm of chromosome 17
      with evidence for a specific target region.
AB  - Allelic loss is a common mechanism of inactivation of tumour-suppressor genes in
      colorectal carcinomas. A number of known or putative tumour-suppressor genes
      including NF1, BRCA1, NME1, NME2 and prohibitin are present on the long arm of
      chromosome 17, and this region has not been extensively analysed in colorectal
      tumours. In this study 72 colorectal carcinomas were examined for allelic loss at
      eight loci on chromosome 17. Allelic loss was frequent both at the p53 locus,
      which is known to be important in colorectal carcinoma, and also telomeric to p53
      on 17p. Allelic loss continued to be present in more than 50% of cases in the
      pericentromeric region and on proximal 17q to the marker LEW101 (D17S40) at 17q22
      23. The most telomeric markers on 17q showed lower rates of allelic loss.
      Analysis of cases with partial deletions which did not include the p53 locus
      showed a common region of overlap of the deletions centred on D17S40. This
      suggests the target of allelic loss on 17q is a tumour-suppressor gene in this
      region.

PMID- 7734303
TI  - Expression of sialyl-Tn in gastric cancer: correlation with known prognostic
      factors.
AB  - Sialyl-Tn (STn) is a core region carcinoma-associated carbohydrate determinant
      expressed on cancer-associated mucins. Expression of STn has been associated with
      poor prognosis in colon and ovarian cancer, independent of other prognostic
      factors such as tumour grade, stage or histological type. Recent studies have
      suggested that STn expression may be an independent prognostic variable in
      gastric cancer. We have examined 158 patients with gastric cancer using the
      antibody B72.3 (Biomira, Edmonton, Alberta, Canada). Of these, 110 patients (70%)
      expressed STn. Expression of STn did not correlate with tumour differentiation or
      the Ming classification, but expression was noted more frequently in the
      relatively good prognosis intestinal type of tumours (chi 2 = 6.9, P = 0.03).
      Conversely, early-stage cancers showed a significantly lower frequency of
      expression than more advanced cases (chi 2 = 13.75, P = 0.003). In this patient
      group, STn expression did not influence survival, and in multivariate regression
      analysis only tumour stage and Lauren classification were found to be independent
      prognostic variables.

PMID- 7734304
TI  - Normal colonic mucosa in hereditary non-polyposis colorectal cancer shows no
      generalised increase in somatic mutation.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) has recently been linked to
      germline defects of DNA repair genes. Colorectal tumours in HNPCC frequently show
      DNA microsatellite instability, but it is not certain whether this mutator
      phenotype occurs throughout the morphologically normal colonic mucosa. We have
      previously used the mPAS histochemical technique in human colorectal mucosa to
      identify a polymorphism for O-acetyltransferase activity that shows monogenic
      inheritance and to show that crypt-restricted loss of O-acetyltransferase
      activity in heterozygotes is due to somatic mutation. We have now used this
      histochemical technique to measure the somatic mutation frequency in the
      uninvolved colon of 12 heterozygous patients with HNPCC, 15 with ileocaecal
      Crohn's disease and 16 with sporadic colorectal cancer (CRC). HNPCC patients
      showed a significant increase in mutation frequency with age (Mann-Whitney U, P =
      0.02). In HNPCC patients aged < 49 years the mean stem cell mutation frequency
      was significantly lower than in the slightly younger group of patients with
      Crohn's disease (0.8 +/- 0.9 x 10(-4) vs 3.5 +/- 3.3 x 10(-4), P < 0.01),
      probably reflecting an increased mutation rate relating to chronic mucosal damage
      in Crohn's disease. Although not statistically significant, the stem cell
      mutation frequency was slightly less in HNPCC patients > 50 years than in
      sporadic CRC cases (4.9 +/- 3.4 x 10(-4) vs 5.9 +/- 3.6 x 10(-4), P > 0.5). We
      conclude that germline defects in HNPCC do not result in a generalised increase
      in liability to mutation in normal colonic mucosa but that a second, somatic,
      event is required. We postulate that this second event occurs in crypt stem cells
      at low frequency, giving rise to scattered individual crypts composed of mutation
      prone cells. The cells in these crypts are then at high risk of acquiring the
      mutations that lead to adenomas, and to rapid progression to carcinoma.

PMID- 7734305
TI  - High-affinity binding sites for gastrin-releasing peptide on human colorectal
      cancer tissue but not uninvolved mucosa.
AB  - Human colorectal cancer tissue and matched uninvolved mucosa from 21 patients
      were examined by radioligand displacement for the presence of binding sites for
      bombesin-like peptides. Five cancers, but no uninvolved mucosa, expressed high
      affinity, low-capacity bombesin binding sites (Kd = 6.53 nM, Bmax = 58.6 fmol mg
      1 protein) of the gastrin-releasing peptide (GRP)-preferring subtype (IC50 4.8
      nM). Bombesin-like peptides may have a role in the pathogenesis of colorectal
      cancer, and bombesin receptor antagonists may be of value in the treatment of
      receptor-positive tumours.

PMID- 7734306
TI  - The association of preoperative serum tumour markers with Dukes' stage and
      survival in colorectal cancer.
AB  - The tumour markers carcinoembryonic antigen (CEA), tissue polypeptide antigen
      (TPA), TPS, CA 19-9, CA 50 and CA 242 were analysed in serum from 203 potentially
      curable colorectal cancer patients. The levels of all markers increased with
      increasing tumour stage, and all markers correlated with survival. Multivariate
      analyses indicated that the Dukes stage had the best prognostic explanatory
      power, followed by TPA. In the subset of 166 potentially cured patients, the
      prognostic information by the markers was substantially reduced. We conclude that
      preoperative serum tumour marker measurements have the potential to aid therapy
      selection, but also that their clinical usefulness is not immediately apparent.

PMID- 7734307
TI  - Serum levels of interleukin 6 in patients with lung cancer.
AB  - Serum interleukin 6 (IL-6) levels were measured in 75 patients with lung cancer
      and in 20 patients with benign lung diseases. IL-6 was detectable in 29 patients
      with lung cancer (39%), but was not detectable in any of the patients with benign
      lung diseases. Serum C-reactive protein levels and plasma fibrinogen levels were
      significantly higher and serum albumin concentration was significantly lower in
      lung cancer patients with detectable serum IL-6 levels than in those without
      detectable serum IL-6 levels and in patients with benign lung diseases. On the
      other hand, no significant difference was observed in blood platelet counts in
      these three groups. Moreover, serum IL-6 levels were not significantly different
      in lung cancer patients with or without clinically demonstrated distant
      metastasis. These results suggest that IL-6 may be a mediator of various
      reactions including an inflammatory response in lung cancer patients.

PMID- 7734308
TI  - Deoxythymidine kinase in the tumour cells and serum of patients with non-Hodgkin
      lymphomas.
AB  - The levels of deoxythymidine kinase in tumour cells (C-TK) and in serum (S-TK)
      were investigated and the tumour volume calculated in 89 patients with non
      Hodgkin lymphoma (NHL), in order to ascertain the importance of C-TK and tumour
      burden as regards the S-TK levels. Among all patients, a correlation was seen
      between S-TK and tumour volume but not between S-TK and C-TK. However, within
      different tumour volume categories (small, medium-sized and large), there was a
      correlation between S-TK and C-TK. Multiple regression analysis supported this
      notion. C-TK correlated with the proliferation-associated parameters, S-phase
      fraction and mitotic index. As already known, S-TK was found to have a strong
      prognostic value. C-TK and tumour burden were also of prognostic value. In
      multivariate analyses, C-TK and tumour volume did not provide prognostic
      information in addition to S-TK, whereas, in the absence of S-TK, C-TK and tumour
      volume did provide additional information. It is concluded that the serum level
      of TK depends on both the tumour burden and the tumour cell proliferation rate.
      Based upon estimations of S-TK in patients assessed shortly after chemotherapy,
      we also suggest that S-TK reflects the number of proliferating cells that have
      died during the period immediately before sampling.

PMID- 7734309
TI  - Pathological prognostic factors in the second British Stomach Cancer Group trial
      of adjuvant therapy in resectable gastric cancer.
AB  - The second British Stomach Cancer Group trial was a prospective randomised
      controlled trial of adjuvant radiotherapy or cytotoxic chemotherapy after
      gastrectomy for adenocarcinoma. It recruited between 1981 and 1986. No survival
      advantage has been demonstrated for the patients receiving either type of
      adjuvant therapy compared with those undergoing surgery alone. We report on 436
      patients randomised into the trial together with 203 patients, who did not fulfil
      the trial criteria, referred to the trial. A univariate (log-rank) analysis of
      pathological factors obtained from the local referring centres showed that tumour
      size, macroscopic type, number os sites involved, depth of invasion, involvement
      of resection lines and lymph nodes and histological grade were significant
      determinants of survival. Histological review by two experienced
      histopathologists found that the Lauren classification and histological grade,
      but not the Ming classification, were significant prognostic factors. The degree
      of lymphocytic and eosinophilic infiltration and presence of dysplasia assessed
      by one of the pathologists showed a significant correlation with survival.
      However, inter-observer correlation for these histological parameters and grade
      was poor. Multivariate analysis identified only depth of invasion, resection line
      and nodal involvement as significant independent pathological variables
      influencing survival. This study confirms the need for expert preparation of the
      resected specimen to obtain the important information on depth of invasion and
      nodal status and also reveals some variation in histological assessment,
      particularly grading, in gastric carcinoma.

PMID- 7734310
TI  - Combination goserelin and tamoxifen therapy in premenopausal advanced breast
      cancer: a multicentre study by the ITMO group. Italian Trials in Medical
      Oncology.
AB  - It has been suggested that tamoxifen may improve the efficacy of medical
      castration with luteinising hormone-releasing hormone analogues, but very few
      data have so far been published concerning the clinical and endocrinological
      activity of this therapeutic modality. In this phase II multicentre trial
      conducted by the Italian Trials in Medical Oncology group (ITMO), 64
      premenopausal patients with hormone receptor-positive or unknown breast cancer
      were treated with monthly s.c. injections of goserelin 3.6 mg, in association
      with a tamoxifen daily dose of 20 mg, as first-line therapy for their advanced
      disease. All of the patients were evaluable for efficacy and there was an overall
      response rate of 41% (95% confidence interval 28-52%), with 7 of the 26
      responders achieving complete remission. The median time to response was 4 months
      (range 2-17), and the median response duration was 13 months (range 6-37 +).
      Better responses were observed in soft tissues (51%); the response in visceral
      and bone metastases was respectively 19% and 37%. Serum concentrations of
      gonadotrophins and oestradiol were significantly decreased by the treatment,
      oestrogen levels being constantly suppressed to within the range observed in post
      menopausal women. No significant change was detected in serum testosterone
      levels. In our experience, although it was not associated with any increased
      clinical efficacy, the concurrent use of goserelin and tamoxifen proved to be a
      feasible approach in the management of premenopausal advanced breast cancer.

PMID- 7734311
TI  - Computer-based interaction analysis of the cancer consultation.
AB  - There are few data available on which to base recommendations for effective
      communication in the cancer consultation. This paper describes a computerised
      interaction analysis system designed specifically for the cancer consultation and
      its application in a study investigating the relationship between doctor-patient
      behaviour and patient outcomes. One hundred and forty-two cancer patients
      attending their first consultation with a cancer specialist were audio taped and
      a copy of the tape was retained for interaction analysis. Before the consultation
      patient anxiety and information and involvement preferences were measured.
      Outcomes included recall of information, patient satisfaction with the
      consultation and psychological adjustment to cancer. Doctor behaviour was shown
      to vary significantly according to the age, sex, involvement preferences and
      in/out-patient status of the patient. The ratio of doctor to patient talk was
      related to satisfaction with communication, while patients whose questions were
      answered showed better psychological adjustment at follow-up. The results suggest
      that patient-centred consultations lead to improved satisfaction and
      psychological adjustment. These data provide precise information about
      consultation behaviour which can be used in the documentation of current practice
      and the evaluation of new interventions to improve communication.

PMID- 7734312
TI  - Salvage therapy of germ cell tumours.

PMID- 7734313
TI  - Exceptional sensitivity of testicular germ cell tumour cell lines to the new anti
      cancer agent, temozolomide.
AB  - Metastatic testicular germ cell tumours are cured in approximately 85% of
      patients using cisplatin-based combination chemotherapy. Patients who fail to
      respond have a poor prognosis, and there is a need for more effective treatments
      for cisplatin-resistant disease. In this study, it is shown that two of four cell
      lines derived from human non-seminomatous testicular germ cell tumours are
      exceptionally sensitive to temozolomide, a new imidazotetrazine which can cross
      the blood-brain barrier in mice. In addition, three pairs of cisplatin-resistant
      sublines show little cross-resistance to temozolomide. These data suggest that
      temozolomide might have activity against non-seminomatous testicular germ cell
      tumours which have relapsed following cisplatin-containing chemotherapy, and
      could have a role in the treatment of patients with metastatic lesions in the
      brain.

PMID- 7734314
TI  - Expression of multidrug resistance-associated protein (MRP), MDR1 and DNA
      topoisomerase II in human multidrug-resistant bladder cancer cell lines.
AB  - The acquisition of the multidrug resistance phenotype in human tumours is
      associated with an overexpression of the 170 kDa P-glycoprotein encoded by the
      multidrug resistance 1 (MDR1) gene, and also with a 190 kDa membrane ATP-binding
      protein encoded by a multidrug resistance-associated protein (MRP) gene. Human
      bladder cancer is a highly malignant neoplasm which is refractory to anti-cancer
      chemotherapy. In order to understand the mechanism underlying multidrug
      resistance in bladder cancer, we established three doxorubicin-resistant cell
      lines, T24/ADM-1, T24/ADM-2 and KK47/ADM, and one vincristine-resistant cell
      line, T24/VCR, from human bladder cancer T24 and KK47 cells respectively. Both
      T24/ADM-1 and T24/ADM-2 cells which had elevated MRP mRNA levels showed both a
      cross-resistance to etoposide and a decreased intracellular accumulation of
      etoposide. T24/VCR cells which had elevated levels of MDR1 mRNA and P
      glycoprotein but not of MRP mRNA, showed cross-resistance to doxorubicin. On the
      other hand, KK47/ADM cells, which had elevated levels of both MRP and MDR1 mRNA
      and a decreased level of topoisomerase II mRNA, were found to be cross-resistant
      to etoposide, vincristine and a camptothecin derivative, CPT-11. Our present
      study demonstrates a concomitant induction of increased levels of MRP mRNA,
      decreased levels of topoisomerase II mRNA and decreased drug accumulation during
      development of multidrug resistance in human bladder cancer cells. The enhanced
      expression of the MRP gene is herein discussed in a possible correlation with the
      decreased expression of the topoisomerase II gene.

PMID- 7734315
TI  - Rapid up-regulation of mdr1 expression by anthracyclines in a classical multidrug
      resistant cell line.
AB  - Studies were carried out in a variant human multidrug-resistant (MDR) cell line
      CEM/A7R, which expresses very low levels of mdr1 mRNA and P-glycoprotein (P-gp).
      The induction of mdr1 RNA expression by three anthracyclines, (doxorubicin,
      daunorubicin, epirubicin), VP-16 and two vinca alkaloids (vincristine,
      vinblastine) was semiquantitatively assessed by scanning Northern blots on a
      phosphorimager. The relative level of mdr1 expression was expressed as ratio of
      mdr1 to the internal RNA (actin). A significant increase (P < 0.02) in expression
      of mdr1 was noted within 4 hrs of exposure to 1.5 micrograms ml-1 daunorubicin or
      epirubicin. Neither vinblastine nor vincristine had any effect on mdr1 levels
      after an 8 h exposure. With increasing concentrations of daunorubicin or
      epirubicin in a fixed 24 h time period, mdr1 expression increased, although a
      biphasic response was seen. Based on MRK 16 binding, an increase in P-gp levels
      was seen in the CEM/A7R line after a 24 h exposure to 1 microgram ml-1
      daunorubicin or epirubicin. The rapid increase in mdr1 expression after a short
      period of exposure to doxorubicin, daunorubicin or epirubicin suggests that
      induction of mdr1 expression may have an important role in the development of
      drug-resistant tumours.

PMID- 7734316
TI  - Induction of apoptosis by anti-cancer drugs with disparate modes of action:
      kinetics of cell death and changes in c-myc expression.
AB  - Incubation of CCRF CEM C7A human lymphoblastic leukaemia cells with etoposide
      (VP16) or N-methylformamide (NMF) induced apoptotic cell death. The kinetics of
      onset of apoptosis was determined and compared with that for dexamethasone
      treated cells. The drugs induced 50% apoptosis at different rates: etoposide by
      approximately 18 h, NMF by 40 h and dexamethasone (DEX) by 52 h. In each case,
      the onset of apoptosis above 10% was preceded by a delay period. This was 8 h for
      etoposide, between 8 and 12 h for NMF and 36 h for dexamethasone. When cells were
      incubated for 36 h with dexamethasone and the drug washed out, addition of NMF
      induced apoptosis without any delay, suggesting that certain common biochemical
      events are required to prime the cells for apoptosis. However, cells treated for
      8 h with NMF did not undergo immediate apoptosis on the addition of DEX. Analysis
      of the cellular content of the c-myc protein showed this to be undetectable by 2,
      6 and 12 h after treatment with etoposide, NMF and DEX respectively. The rapid
      onset of NMF-induced cell death after a 36 h DEX pretreatment occurred 24 h after
      the loss of expression of c-Myc protein, suggesting that the expression of c-myc
      is not required for drug-induced cell death. In contrast to DEX-induced
      apoptosis, concomitant incubation of cells with NMF or etoposide and 200 nM of
      the protein synthesis inhibitor cycloheximide did not inhibit apoptotic cell
      death. The idea that drugs with different modes of action initiate conserved
      responses which engage a programmed cell death is discussed.

PMID- 7734317
TI  - Nitric oxide inhibition sustains vasopressin-induced vasoconstriction.
AB  - Hepatic parenchymal vasoconstriction increases cytotoxic drug uptake into hepatic
      metastases by increasing the tumour to liver blood flow ratio. Prolonged infusion
      of the vasoconstrictor vasopressin does not result in sustained vasoconstriction,
      and this may limit the benefit of vasopressin in infusional chemotherapy. We have
      assessed whether loss of vasopressin-induced vasoconstriction is mediated by
      nitric oxide. Hepatic and tumour blood flow were continuously monitored, in an
      animal hepatic tumour model, by laser Doppler flowmetry. The response to
      regionally infused vasopressin and the nitric oxide inhibitor N-nitro-L-arginine
      methyl ester (L-NAME) were assessed over a 30 min infusion period. The
      vasopressin-induced vasoconstrictor effect diminished after 15 min despite
      continued infusion. Vasoconstriction was significantly prolonged when L-NAME was
      infused in addition to vasopressin. The increase in tumour to normal blood flow
      ratio was greater over the infusion period when L-NAME was co-administered with
      vasopressin. Our results suggest that the loss of vasopressin-induced
      vasoconstriction seen in liver parenchyma after regional infusion is prevented by
      the nitric oxide synthase inhibitor L-name and may be mediated by nitric oxide.

PMID- 7734318
TI  - The effects of carbogen and nicotinamide on intravascular oxyhaemoglobin
      saturations in SCCVII and KHT murine tumours.
AB  - Considerable effort has been focused on devising methods for manipulating tumour
      oxygenation and thereby improving tumour radiosensitivity. The combination of
      nicotinamide and carbogen has been proposed to oxygenate both chronically and
      acutely hypoxic cells in tumours. However, results have varied markedly with both
      tumour model and measurement technique. The current objectives were (1) to
      determine whether changes in radiosensitivity following oxygen manipulation
      correlated with changes in tumour oxygenation and (2) to assess whether
      oxygenation was preferentially improved in specific tumour micro-regions. Using
      two murine tumour lines, the SCCVII carcinoma and the KHT sarcoma, tumour
      intravascular HbO2 saturations were measured cryospectrophotometrically following
      nicotinamide, carbogen or the combination. Generally, nicotinamide had minor
      effects on oxygenation, arguing against a substantial effect on acute hypoxia,
      while carbogen and the combination produced marked and equivalent improvements in
      oxygen availability. These results demonstrate that changes in tumour
      radiosensitivity may not agree with corresponding changes in oxygenation, even
      within a given tumour model, and that the efficacy of a given manipulative agent
      may vary substantially with tumour line. One possible explanation for these
      findings is that different subpopulations of clonogenic vs non-clonogenic cells
      may be oxygenated by alternative treatments.

PMID- 7734319
TI  - Anti-tumour activity of photodynamic therapy in combination with mitomycin C in
      nude mice with human colon adenocarcinoma.
AB  - The interaction of photodynamic therapy (PDT) and a chemotherapeutic drug,
      mitomycin C (MMC), was investigated using WiDr human colon adenocarcinoma tumours
      implanted on Balb/c athymic nude mice. The WiDr tumours were treated with PDT
      alone, MMC alone or with both. It was found that the combined treatment produced
      a greater retardation in the growth of the WiDr tumour than monotherapy with MMC
      or PDT. The synergistic effect was especially prominent when PDT was used in
      combination with a low dose of MMC (1 mg kg-1), since treatment of 1 mg kg-1 MMC
      alone had no effect on the tumour. The anti-tumour activity of PDT was found to
      be increased with MMC of 5 mg kg-1. The response of normal skin on mice feet to
      PDT slightly greater when PDT was combined with 5 mg kg-1 MMC than when PDT was
      applied alone, while no detectable additional effect on skin photosensitivity was
      observed when PDT was combined with 1 mg kg-1 MMC. An enhanced uptake of
      Photofrin in tumours was found 12 h and 24 h after administration of MMC. The
      effect of MMC on the cell cycle distribution of cell dissociated directly from
      the tumours was studied. The results suggest that the increased susceptibility to
      photoinactivation of Photofrin-sensitised tumours may be due to MMC-induced
      accumulation of the tumour cells in S-phase.

PMID- 7734320
TI  - Cellular pharmacology of a liposomal preparation of N4-hexadecyl-1-beta-D
      arabinofuranosylcytosine, a lipophilic derivative of 1-beta-D
      arabinofuranosylcytosine.
AB  - The in vitro deamination, cytotoxicity, cellular drug uptake, distribution and
      cellular pharmacology in HL-60 cells of N4-hexadecyl-1-beta-D
      arabinofuranosylcytosine (NHAC), a lipophilic derivative of
      arabinofuranosylcytosine (ara-C), were studied. Compared with ara-C, NHAC in
      liposomal formulations was highly resistant to deamination, resulting in levels
      of formation of arabinofuranosyluracil 42 and ten times lower in plasma and liver
      microsomes respectively. The cytotoxicity of NHAC was independent of both the
      nucleoside transporter mechanism and the deoxycytidine (dCyd) kinase activity as
      demonstrated by co-incubating NHAC with dipyridamole and/or dCyd. In ara C
      resistant HL-60 cells NHAC was still cytotoxic, requiring drug concentration only
      1.6 times higher than sensitive cells. Uptake of NHAC was six times higher and
      was not inhibited by dipyridamole. The pharmacokinetics of NHAC revealed that its
      intracellular half-life is 4.8 times longer than that of ara-C. Ara-CTP formation
      and incorporation into DNA was up to 25-50 times lower than that of ara-C and
      contributed only marginally to the cytotoxic effects of NHAC. These results
      indicate that, because of the significantly increased stability, the transporter
      independent uptake and the dCyd-kinase-independent cytotoxicity, NHAC might be
      active in ara-C-resistant cells.

PMID- 7734321
TI  - Molecular design of hybrid tumour necrosis factor alpha with polyethylene glycol
      increases its anti-tumour potency.
AB  - This study was conducted to increase the anti-tumour potency and reduce the toxic
      side-effects of tumour necrosis factor alpha (TNF-alpha). Natural human TNF-alpha
      was chemically conjugated with monomethoxy polyethylene glycol (PEG) using
      succinimidyl coupling of lysine amino groups of TNF-alpha. The number-average
      molecular weight of PEG-modified TNF-alpha (PEG-TNF-alpha) increased with an
      increase in the reaction time and the initial molar ratio of PEG relative to TNF
      alpha. The resulting modified TNF-alpha was separated into fractions of various
      molecular weights. The specific activity of separated PEG-TNF-alpha s relative to
      that of native TNF-alpha gradually decreased with an increase in the degree of
      PEG modification, but the plasma half-life was drastically increased with the
      increase in molecular weight of modified TNF-alpha. PEG-TNF-alpha s, in which 29%
      and 56% of lysine residues were coupled to PEG, had anti-tumour activity
      approximately 4 and 100 times greater than unmodified TNF-alpha in the murine
      Meth-A fibrosarcoma model. Extensive PEG modification did not increase its in
      vivo activity. A high dose of unmodified TNF-alpha induced toxic side-effects,
      but these were not observed with the modified TNF-alpha s. Optimal PEG
      modification of TNF-alpha markedly increased its bioavailability and may
      facilitate its potential anti-tumour therapeutic use.

PMID- 7734322
TI  - Prolonged survival of mice with human gastric cancer treated with an anti-c-ErbB
      2 monoclonal antibody.
AB  - A monoclonal antibody (MAb), 4D5, specifically recognising an extracellular
      epitope of the c-ErbB-2 protein, inhibited the growth of human gastric cancer
      overexpressing c-ErbB-2 severe combined immunodeficient (SCID) mice. This
      antibody also reduced the mass of established tumours xenografted into SCID mice,
      whereas gastric cancer not expressing c-ErbB-2 exhibited no regression in
      response to 4D5 treatment. In addition, administration of 4D5 prevented
      colonisation of cancer cells and prolonged the survival of host SCID mice
      inoculated i.v. with c-ErbB-2-overexpressing tumour cells. This is the first
      reported study to show that treatment with a single antibody specific to c-ErbB-2
      prolongs the survival of host SCID mice bearing xenotransplanted tumours.

PMID- 7734323
TI  - Coexpression of wild-type and variant oestrogen receptor mRNAs in a panel of
      human breast cancer cell lines.
AB  - Wild-type as well as variant oestrogen receptor (ER) mRNAs with exon 5 and 7
      deleted were identified in a panel of human breast tumour cell lines by reverse
      transcriptase-polymerase chain reaction followed by dideoxynucleotide sequence
      analysis, and then quantitated by ribonuclease protection analysis. All cell
      lines categorised as ER+ by ligand-binding analysis expressed both wild-type and
      variant ER transcripts. Most cell lines classified as ER- did not express any ER
      transcript. However, three ER- cell lines (BT-20, MDA-MB-330 and T47Dco)
      expressed both wild-type and variant transcripts. A differential pattern of
      expression of wild type to variant was seen in both ER+ and ER- cell lines,
      however this pattern was not paralleled by differences in ligand-binding
      activity. Breast tumour cell lines previously classified as ER- expressed
      significantly lower levels of ER transcripts than did their ER+ counterparts. In
      view of these findings, as well as earlier reports that the exon 5 deletion ER
      variant encodes a dominant-positive receptor, it seems clear that some cell lines
      are misclassified as ER-, and express both wild-type and variant ER mRNAs, and
      that the overexpression of this variant may account, in part, for their oestrogen
      independent phenotype.

PMID- 7734324
TI  - Amplification of the MDM2 gene in human breast cancer and its association with
      MDM2 and p53 protein status.
AB  - The present study reports on the frequency of MDM2 gene amplification and MDM2
      protein expression in a series of 100 breast carcinomas and its association with
      accumulation of the p53 protein. Of the 100 cases, frozen samples for 82 cases
      were available for Southern blotting. Three of the 82 (4%) demonstrated MDM2 gene
      amplification of up to 6-fold. Immunohistochemical analysis of the formalin
      fixed, paraffin-embedded tumours demonstrated that 7/97 (7%) had nuclear
      expression for MDM2 in 10-50% of the tumour cells (type 2 staining) and were
      denoted MDM2+. Two of the MDM2-amplified samples were MDM2+ with one of the two
      tumours also displaying type 2 p53 nuclear staining. Finally at the protein
      level, MDM2+ tumours were significantly associated with tumours having low levels
      of p53 staining (0-10% cells positive) (P = 0.03). We conclude that MDM2 gene
      amplification occurs at a lower frequency in breast cancer than in non-epithelial
      tumours. Alterations in MDM2 and p53 may represent alternative pathways in
      tumorigenesis, but they are not mutually exclusive in all cases.

PMID- 7734325
TI  - Delivery of the ribosome-inactivating protein, gelonin, to lymphoma cells via
      CD22 and CD38 using bispecific antibodies.
AB  - It is well established that bispecific antibodies (BsAbs) can be used effectively
      in targeting the ribosome-inactivating protein (RIP), saporin, against neoplastic
      B cells. We have now extended this delivery system for use with gelonin. By
      measuring antigen-binding characteristics and epitope mapping a panel of anti
      gelonin MAbs using the IAsys resonant mirror bisensor, we were able to rapidly
      select the most suitable for making BaAbs. The Fab' fragments from these MAbs
      were chemically conjugated with Fab' from either anti-CD22 or anti-CD38.
      Cytotoxicity assays showed that BsAbs were highly efficient at delivering gelonin
      to cultured Daudi cells and achieved levels of toxicity which correlated closely
      with the affinity of the BsAbs. Using pairs of anti-CD22 BsAbs we were able to
      generate bivalent BsAb-gelonin complexes which achieved IC50 values of 2 x 10(
      11) M gelonin, a potency which is equivalent to that reached by saporin in this
      targeting system. However, because gelonin is 5-10 times less toxic than saporin,
      the therapeutic ratio for gelonin is superior, making it potentially a more
      useful agent for human treatment. Cytotoxicity assays and kinetic analysis showed
      that targeting gelonin via CD38 was 2-5 times less effective than delivery
      through CD22. However, with a pair of BsAbs designed to co-target gelonin via
      CD22 and CD38, the cytotoxicity achieved equalled that obtained with a pair of
      anti-CD22 BsAbs (IC50 = 1 x 10(-11) M). This important result suggests that the
      anti-CD38 helps bind the gelonin to the cell and is then 'dragged' or 'piggy
      backed' into the cell by the anti-CD22 BsAb. The implication of these findings
      for cancer therapy is discussed.

PMID- 7734327
TI  - British Connective Tissue Society Meeting. Cardiff, September 1994. Abstracts.

PMID- 7734326
TI  - Frequent loss of heterozygosity on chromosome 17 at 17q11.2-q12 in Barrett's
      adenocarcinoma.
AB  - Allelic loss on chromosome 17 in 18 Barrett's oesophageal tumours was analysed
      with 17 polymorphic microsatellite markers. Loss of heterozygosity (LOH) of one
      or more markers was seen in 72% (13 of 18) tumours on 17p and 56% (10 of 18) on
      17q. The highest 17p losses were found at D17S799 (62%, five of eight) and
      D17S261 (55%, five of nine), while loss at the p53 locus was 31% (5 of 16). The
      highest loss on 17q was found at the TCF-2 (17q11.2-q12) locus with 66% (8 of 12)
      LOH. TCF-2 was the only marker lost in two of the tumour samples; furthermore,
      TCF-2 was lost in four other tumours which retained heterozygosity at the markers
      on either side of it, D17S261 and D17S740. Six markers were used to assess LOH at
      17q11.2-q12, and five of eight of the tumour specimens which had LOH at TCF-2 had
      no other loss on 17q. No statistically significant correlations were found
      between loss on 17q or 17p and any clinicopathological parameters. We propose
      from these data that the 17q11.2-q12 region contains a novel predisposing gene in
      Barrett's adenocarcinomas and may represent the site of a tumour-suppressor gene.

PMID- 7734328
TI  - Inflammation: John Hunter's "A treatise on the blood, inflammation and gun-shot
      wounds".
AB  - John Hunter's A Treatise on the Blood, Inflammation and Gunshot Wounds was
      published in 1794. Throughout the nineteenth century this was considered the most
      important study of inflammation and has been widely quoted since. After a section
      on the nature of blood and the circulatory system, in which he describes the
      vascular supply in detail, he passes on to an extensive survey of inflammation.
      This is based mainly on his wide clinical experience, including that as a
      military surgeon. He, however, supplements this with a number of experiments,
      some of which are classic. He bases his observations on the four cardinal signs
      of Celsus (redness, heat, swelling and pain). Inflammation is then divided into
      three main groups: adhesive, suppurative and ulcerative. He discusses the nature
      of pus and the formation and treatment of abscesses. He describes his experiments
      on the transplantation of tissues under the general heading of adhesive
      inflammation. This, he states, underlies the union of wounds and thus the union
      of tissues after transplantation. Although unaware of the role of infecting
      organisms as a cause of inflammation, he makes observations on inflammation in
      smallpox, venereal infections and tuberculosis. He relates these to his
      observations on inflammatory aspects of wound healing. Lister was particularly
      influenced by Hunter's observations in the development of antisepsis. As well as
      the local effect of inflammation, Hunter was concerned with the constitutional
      effects such as fever.

PMID- 7734329
TI  - Human mast cells produce type VIII collagen in vivo.
AB  - Mast cells are assuming importance not only in their familiar role in acute
      allergic and parasitic diseases but also in chronic inflammatory, immunologic and
      fibrotic states. The processes by which human extracellular matrices are
      influenced by mast cells have remained obscure. We report here the production of
      type VIII collagen by human mast cells. Mast cells representing each of the known
      phenotypes were identified in a variety of tissues using histochemical
      techniques, and monoclonal antibodies specific for tryptase, chymase, and c-kit.
      Mast cells in normal and pathologic tissues expressed type VIII collagen alpha-1
      chain protein and mRNA, detected by immunohistochemistry using monoclonal and
      polyclonal antibodies, and non-isotopic oligonucleotide in situ hybridization
      using digoxigenin-labelled oligonucleotide probes based on the published human
      alpha-1 collagen VIII sequence. Perivascular location of type VIII collagen
      positive mast cells was a striking finding. The secretion of type VIII collagen
      by mast cells in vivo may contribute to angiogenesis, tissue remodelling, and
      fibrosis.

PMID- 7734330
TI  - Juxtaposition of peroxisomes and chromosomes in mitotic hepatocytes following
      methyl clofenapate administration to rats.
AB  - Administration of 25 mg/kg/day methyl clofenapate to Alpk/APfSD rats for up to 4
      days gave rise to hepatomegaly resulting from a combination of hepatocyte
      hyperplasia, mainly in the periportal region of the lobule, and centrilobular
      cell hypertrophy. In hepatocytes undergoing mitosis there was a redistribution of
      dense vesicles and some peroxisomes to the perinuclear region of the cytoplasm.
      With increasing length of exposure to methyl clofenapate the number of
      peroxisomes located in this region during mitosis increased. Chromosomes observed
      by electron microscopy were seen to lie in close apposition to these organelles.
      Immunocytochemical localization of the Phase II conjugating enzymes glutathione-S
      transferase B, C and E showed a dramatic reduction and redistribution of those
      enzymes in mitotic cells and their absence in the region of the chromosomes.
      These events may increase the vulnerability of DNA to damage in specific cells.

PMID- 7734331
TI  - Cocaine hepatotoxicity: a study on the pathogenesis of periportal necrosis.
AB  - Cocaine is reported to produce either periportal or mid-zonal necrosis in mice
      pretreated with the enzyme inducer phenobarbitone (James et al. 1987; Powell et
      al. 1991; Charles & Powell 1992). Dose-response and time course experiments were
      performed in phenobarbitone treated male DBA/2Ha mice to study the pathogenesis
      of this unusual cocaine induced lesion. An increase in the dose of cocaine from
      60 to 90 or 120 mg/kg produced more extensive and severe periportal and linking
      portal damage and elevated plasma aspartate (AST) and alanine (ALT)
      aminotransferases in a dose dependent manner. Scattered hepatocyte degeneration
      began at the edge of the periportal region and was detectable by electron
      microscopy within 30 minutes of administration of 60 mg/kg of cocaine, with
      conspicuous disorganization of the endoplasmic reticulum being one of the
      earliest changes. Significant elevations of plasma AST and ALT were observed 3
      hours after cocaine administration and were sustained for 12 hours, at which time
      progressive hepatocyte damage had developed into a network of confluent necrosis
      at the periphery of the periportal region. The rapidity of organelle derangement
      and subsequent cell death, and absence of any effect on total cytochrome P-450 or
      FAD-mono-oxygenase levels, appear to distinguish this periportal lesion from
      previous reports of cocaine induced centrilobular necrosis in non-enzyme induced
      mice, suggesting that the two types of damage may develop by different
      mechanisms. The observation that periportal lesions commence at the periphery of
      the periportal area, progressing portalwards with increasing dose and time,
      offers an explanation for the previously conflicting reports of cocaine induced
      mid-zonal and/or periportal lesions in phenobarbitone treated mice.

PMID- 7734332
TI  - Ultrastructural alterations of hepatocytes in the tumour-bearing, cachectic rat.
AB  - Morphologic changes in the hepatocytes of tumour-bearing rats at the pre
      cachectic and cachectic stages were studied by electron microscopy and were
      quantitatively analysed by a morphometric method. Ten male F-344 rats,
      subcutaneously inoculated with methylcholanthrene-induced sarcoma cells (TBR)
      were compared with ten pair-fed controls (CTR). There was no significant
      difference in the size of the cells or their nuclei, the number of mitochondria,
      or the number of lysosomes, between TBR and CTR at either the pre-cachectic or
      cachectic stage. Although the size of mitochondria of TBR was already
      significantly enlarged at the pre-cachectic stage, before the food intake of the
      TBR had decreased, the micro-structure within the mitochondria was unaltered.
      Marked differences were observed in the number, arrangement and distribution of
      the rough endoplasmic reticulum, all of which decreased significantly in TBR
      compared with CTR at both the pericentral and periportal zones. Changes at the
      periportal region were further pronounced at the cachectic stage. These results,
      distinct from the changes seen in simple starvation, may confirm a part of the
      biochemical evidence specific to tumour induced metabolic alterations.

PMID- 7734333
TI  - Suppression of polymorphonuclear leucocyte chemotaxis by Pseudomonas aeruginosa
      elastase in vitro: a study of the mechanisms and the correlation with ring
      abscess in pseudomonal keratitis.
AB  - Bacteria, or the culture supernatants of an elastase non-producing strain of
      Pseudomonas aeruginosa, elicited a chemotactic response from polymorphonuclear
      leucocytes (PMN) in vitro. The chemoattractive capacity was diminished under the
      presence of Boc-Phe-Leu-Phe-Leu-Phe, a receptor antagonist of N-formyl-Met-Leu
      Phe (fMLP) which is a bacterial chemotactic peptide to PMN. This indicated that
      the chemoattractant derived from Pseudomonas aeruginosa was a fMLP-like
      molecule(s). In contrast, culture supernatants of an elastase producing strain of
      Pseudomonas aeruginosa produced negligible chemotactic response from PMN. Indeed,
      an inhibitory effect of the culture supernatants or of purified Pseudomonas
      aeruginosa elastase (PAE) on PMN chemotaxis was observed when fMLP was used as a
      chemoattractant. Another fMLP-induced function of PMN, respiratory burst
      activation, was also diminished by pretreatment of PMN with PAE. PAE hydrolysed
      fMLP at the Met-Leu bond and diminished the chemoattractant capacity. In
      addition, a receptor analysis with fML-3H-P demonstrated a decrease in numbers of
      fMLP receptors on PMN without changing the dissociation constant values after the
      treatment of the cells with PAE. In the primary structure of the fMLP receptor
      previously reported, a preferential amino acid sequence for cleavage by PAE was
      identified in what was believed to be an extracellular portion of the receptor
      molecule. These results suggested that PAE could diminish PMN infiltration in
      response to Pseudomonas aeruginosa in vivo by cleavage of the fMLP-like
      pseudomonal chemotactic ligand and the receptors on PMN.

PMID- 7734334
TI  - Trypanosoma cruzi: histopathology of endocrine system in immunocompromised mice.
AB  - Naturally immunocompromised athymic mice, neonatal mice and adult outbred OFI
      mice treated with the immunosuppressive agents cyclophosphamide (CY),
      dexamethasone (DM) and indomethacin (IM) were infected with trypomastigotes of
      Trypanosoma cruzi Y and CL strains. 10(4) parasites were used, except in the case
      of IM treatment, where mice received 10(3) trypomastigotes in one group and 10(5)
      in another. The course of parasitaemia, tissue distribution of amastigotes and
      time of mortality were compared with an infected thymus intact control group.
      Neonate and indomethacin treated mice presented the same pattern of parasitaemia.
      Death occurred as early as 9-10 days after infection. A single dose of CY 200
      mg/kg given 5 days after infection enhanced the parasitaemia and increased the
      number of parasites in the tissues. All groups were similar in terms of
      colonization of the endocrine system by parasites and the adrenals showed the
      highest density of amastigotes nests. The thyroid gland (analysed only in
      neonates) showed intense amastigote accumulation. Colonization of the ovary was
      observed with amastigotes in both the theca interna and in the stroma. The testes
      (also examined only in the neonate) showed that the interstitial cells, the
      tunica albuginea of the seminiferous tubules and the loose connective tissue were
      infected. Athymic nude mice showed the most intense parasite colonization of the
      islets of Langerhans.

PMID- 7734335
TI  - Effects of chronic fluoride toxicity on the morphology of ductus epididymis and
      the maturation of spermatozoa of rabbit.
AB  - This study used light and scanning electron microscopy to observe the effect of
      chronic fluoride toxicity on the structure of the ductus epididymis, testis and
      spermatozoa in rabbit. The rabbits were treated with 10 mg NaF/kg body weight/day
      for 20 and 23 months. Serum fluoride was estimated by the fluoride ion-specific
      electrode method. Fluoride levels in the sera of both 20 and 23-month treated
      rabbits were significantly increased (P < 0.001). Loss of stereocilia,
      significant decrease (P < 0.001) in the height of the pseudostratified columnar
      epithelium and significant increase (P < 0.001) in the diameter of both the caput
      and cauda ductus epididymis were observed only in the 23-month fluoride treated
      rabbits. The decreases in the epithelial cell height (P < 0.01) and the tubular
      diameter (P < 0.001) of the testis were significant only in 23-month treated
      animals. Spermatozoa in the lumen of the testis of both treated groups of animals
      and in the caput and cauda ductus epididymis of 20-month treated animals appeared
      normal, but spermatozoa in the caput and cauda ductus epididymis of 23-month
      treated animals were fragmented. In the 23-month fluoride treated rabbits, the
      weights of the caput and cauda epididymis were significantly reduced (P < 0.025)
      and there was also a reduction in the number of secretory granules in these
      organs. The structural changes observed in the caput and cauda ductus epididymis
      might adversely affect the maturation of spermatozoa.

PMID- 7734336
TI  - Comparison of splenectomy effects as an indication for host response to growth of
      primary and metastatic tumour cells in two murine tumour systems.
AB  - The tumour-host relation is of extreme complexity; moreover, it may change during
      tumour progression. Information regarding this relation may be of importance in
      appreciating the efficiency of immunotherapy. In the present study, the effect of
      splenectomy on tumour growth in two murine tumour progression models, the Lewis
      lung carcinoma and AKR lymphoma, was examined. The effect of spleen ablation on
      growth of cells derived from primary and metastatic tumour cells was tested. The
      data obtained showed a differential effect of splenectomy on the growth of
      primary versus metastatic tumour cells in the two tumour systems, indicating a
      differential host response induced by the two cell types and/or a differential
      tumour cell sensitivity to immune reactions. Surprisingly, the spleen appeared to
      have a defensive role against metastatic tumour cells and a growth enhancing
      influence on primary tumour cells. The instability of the tumour-host relation
      may have important implications for the chances of immunotherapy to serve as an
      efficient cancer treatment.

PMID- 7734337
TI  - Mercury distribution in the mouse brain after mercury vapour exposure.
AB  - Female SJL/N mice were exposed to mercury vapour 5 days/week for 10 weeks, at a
      mercury concentration of approximately 0.5 mg/m3, 19 h/day; 1 mg/m3, 3 h/day; 0.3
      mg/m3, 6 h/day or 1 mg/m3, 1.5 h/day. The total mercury concentrations in the
      brain were 6.4, 6.3, 1.6 and 0.64 micrograms/g tissue, respectively. The mercury
      distribution in the brains was examined. Mercury was found in almost the whole
      brain in the two groups with the highest exposure. In the third group, mercury
      was primarily found in the neocortical layer V, the white matter, thalamus, and
      the brain-stem. In the fourth group, the white matter and the brain-stem were the
      targets for mercury accumulation. Similarities and differences between rats and
      mice in the distribution pattern are discussed.

PMID- 7734338
TI  - The role of 1,25-dihydroxycholecalciferol and prostaglandin E2 in the regulation
      of human osteoclastic bone resorption in vitro.
AB  - Prostaglandins increase human osteoclast generation in vivo whereas they have
      been shown to exert the opposite effect in vitro: the latter results are based on
      enumeration of osteoclast-like cells, whose nature is controversial. We have
      generated human osteoclasts in vitro as assessed by bone resorption, a function
      unique to the osteoclast, and analysed the role of prostaglandin E2 (PGE2) in
      osteoclast activity. Human bone marrow cells were cultured to form a mature
      stroma and then sedimented onto bone slices with or without a recharge of non
      adherent bone marrow cells. Bone resorption was increased by 1,25
      dihydroxycholecalciferol (1,25(OH)2D3) and PGE2 and inhibited by indomethacin:
      this inhibition was reversed by addition of PGE2. Our work supports the
      observation that PGE2 increases bone resorption in vivo and demonstrates the
      value of assessing osteoclast generation and activity in vitro using bone
      resorption.

PMID- 7734339
TI  - Morphological changes in rat single lung isografts after long-term survival.
AB  - A high priority in organ transplantation research is to increase the number of
      hours that an organ can be successfully preserved. Transplant programmes rely on
      hypothermia and flush solutions to maintain organ viability during the storage
      period. We studied long-term morphology in lungs stored for 24 or 48 hours using
      two modified versions of University of Wisconsin solution, one mimicking the
      extracellular medium and the other the intracellular medium. Four weeks after
      transplantation, X-ray and angiograms were used to assess the proportion of
      ventilating tissue, and light and electron microscopy to analyse morphology.
      Pulmonary tissue presented near-normal histological appearance in well preserved
      areas while fibrosis and chronic inflammation were found in scarring processes.
      Electron microscopy studies revealed some damage-related changes in tissue which
      appeared histologically normal. Four weeks after transplantation, quality and
      quantity of recovery were uniform for both solutions tested after 24 hours of
      storage. However, without reaching significance, after 48 hours the quantity of
      successfully preserved pulmonary tissue was greater in the group stored in the
      intracellular solution.

PMID- 7734340
TI  - Rat ultraviolet ray B photodermatitis: an experimental model of psoriasis
      vulgaris.
AB  - Ultraviolet ray B (UV-B) induced dermatitis in the rat may be a model for human
      psoriasis vulgaris. Detailed studies of this model are reported. Rat skin
      responded to UV-B irradiation quite differently from human, guinea-pig, or mouse
      skin. Rat UV-B dermatitis was characterized by a sharply demarcated brownish-red
      lesion with scale formation lasting for 10 days. Histologically, microvascular
      dilatation, intraepidermal accumulation of polymorphonuclear leucocytes with
      microabscess, mononuclear cell infiltration at the papillary dermis and
      hyperproliferation of epidermal cells were observed. These features were similar
      to those of clinical psoriasis vulgaris in man. Leucocyte suppression, induced by
      systemic ferritin administration to the irradiated rats, resulted in loss of the
      epidermal hyperproliferation and inhibition of the tissue leucocytosis. This
      leucocyte suppression remodelled the picture of the rat UV-B dermatitis into that
      seen in other mammalian species, where microvascular dilatation and degeneration
      of keratinocytes (so-called sunburn cells) are characteristic. The irradiated
      epidermis of the rats treated with ferritin possessed an in vitro PMN chemotactic
      property. Rat UV-B dermatitis seems to be a useful model to investigate
      aetiopathogenic mechanisms in psoriasis vulgaris. However, the former heals after
      injury and does not relapse as does psoriasis.

PMID- 7734341
TI  - Tobacco smoke condensate cutaneous carcinogenesis: changes in Langerhans' cells
      and tumour regression.
AB  - Tobacco smoke condensate was painted on the skin of BALB/c mice. It increased the
      density and changed the morphology of Langerhans' cells (LC). LC number in
      epidermal sheets of treated mice was significantly higher (1793 LC/mm2) than in
      controls (946 LC/mm2) (P < 0.0001) and remained elevated for 35 weeks. LC became
      less dendritic, or even rounded in shape, and smaller in size. The function of
      the morphologically altered LC was impaired when assessed by the contact
      hypersensitivity response. These changes were associated with skin tumour
      development in all treated mice. Ten weeks after stopping the TSC treatment, LC
      number in skin tumours and in skin around these lesions had not decreased, but
      significantly increased (P < 0.0001). During this period tumour regression
      occurred in 23% of tumours; the remaining tumours showed a 50% reduction in size.
      At 45 weeks, the LC number in epidermal sheets around skin papillomas was 2274 +/
      14.14/mm2 and in invasive squamous cell carcinomas was 2088 +/- 183/m2. This was
      associated with reversible changes in LC morphology, where cells became fully
      dendritic. This also correlated with lymphocytic infiltration into tumours,
      tumour necrosis, reduction in tumour size and/or tumour regression. It is
      concluded that the influx of normal LC into the skin tumours allowed the
      development of an immune response with tumour regression.

PMID- 7734342
TI  - Heparin-induced thrombocytopenia.

PMID- 7734343
TI  - Reactivity with erythroid and non-erythroid tissues of a murine monoclonal
      antibody to a synthetic peptide having amino acid sequence common to cytoplasmic
      domain of human glycophorins C and D.
AB  - Three synthetic peptides encompassing the entire cytoplasmic polypeptide sequence
      (amino acid residues 82-128) of glycophorin C (GPC) and glycophorin D (GPD) were
      used to immunize mice for the production of monoclonal antibodies (MoAbs). Only
      the synthetic peptide (GPC-peptide-1) corresponding to C-terminal residues 112
      128 elicited a MoAb (named BGRL-100) which could react with native and denatured
      GPC and GPD. We characterized BGRL-100 by inhibition using GPC-peptide 1 and red
      cell sialoglycoproteins. The ability of BGRL-100 to interact with native GPC and
      GPD was assessed by immunoprecipitation with normal red cells (RBCs), and with
      denatured GPC and GPD by Western blotting of both normal RBCs and RBCs carrying
      GPC variants. Immunohistochemical staining of human tissue sections was performed
      using both BGRL-100 and a rat MoAb (named BRAC-1), which is specific for an
      extracellular domain of GPC and GPD. Both antibodies showed strong staining of
      erythroid lineage haemopoietic cells in fetal liver, sinusoids of adult liver and
      RBCs in the blood vessels of all tissues tested. Neither antibody reacted with
      epithelia from a range of human tissues. However, both MoAbs stained neural
      tissue in a distinctive fibrillar pattern. This suggests the presence of an
      analogue of erythroid GPC in neural tissues.

PMID- 7734344
TI  - Relationship between transfusion regimen and suppression of erythropoiesis in
      beta-thalassaemia major.
AB  - In the management of beta-thalassaemia major, different transfusion schemes are
      employed with baseline haemoglobin levels ranging from 8 to over 12 g/dl. We
      studied the relationship between transfusion regimen and suppression of
      erythropoiesis in 52 patients with beta-thalassaemia major whose mean
      pretransfusion haemoglobin levels ranged from 8.6 to 10.9 g/dl. Multiple,
      regression analysis showed that serum transferrin receptor was the parameter more
      closely related to mean pretransfusion haemoglobin (r = -0.77, P < 0.001). As
      measured through serum transferrin receptor, erythroid activity was 1-2 times
      normal for pretransfusion haemoglobin levels between 10 and 11 g/dl. 1-4 times
      normal for levels from 9 to 10 g/dl, and 2-6 times normal for levels from 8.6 to
      9 g/dl. Mean pretransfusion haemoglobin was also inversely related to serum
      erythropoietin (r = -0.72, P < 0.001), whereas it showed no or a weak
      relationship with Hb F, reticulocyte count, or circulating nucleated red cell
      count. This study suggests that serum transferrin receptor is a reliable
      indicator of suppression of erythropoiesis in beta-thalassaemia major. On the
      basis of our findings, pretransfusion haemoglobin values of < or = 9 g/dl should
      be adopted with caution, because these levels can be associated with an
      insufficient inhibition of erythroid marrow expansion. However, a transfusion
      programme, with a baseline haemoglobin of 9-10 g/dl, may provide enough
      suppression of erythropoiesis and allow a reduction in blood consumption as
      compared with the classic hyper- or supertransfusion schemes. Since fixed
      haemoglobin levels may not be the best target for transfusion treatment in all
      thalassaemic patients, assay of serum transferrin receptor may be helpful for
      individualizing the transfusion regimens.

PMID- 7734345
TI  - Thalassaemia in Vanuatu, south-west Pacific: frequency and haematological
      phenotypes of young children.
AB  - The archipelago of Vanuatu situated in the South-West Pacific has a high
      frequency of alpha + thalassaemia and additionally on some of the islands there
      is a high frequency of beta thalassaemia. As part of a large cohort study to
      investigate the clinical effect of thalassaemia on malaria on the islands of
      Espiritu Santo and Maewo in Vanuatu, the gene frequencies of the thalassaemias
      were determined and blood counts were performed on a cohort of infants from birth
      to 3 years. The haematological phenotypes of the different thalassaemic genotypes
      are compared, providing a detailed description of the clinical manifestations of
      alpha + thalassaemia during early development. In addition, cross-sectional
      surveys of the population of the two islands were performed to establish the
      frequency of thalassaemia and other red cell polymorphisms and their geographical
      distribution.

PMID- 7734346
TI  - alpha-Thalassaemia in the population of Cyprus.
AB  - We have determined the alpha-thalassaemia (alpha-thal) determinants in 78
      patients with Hb H disease from Cyprus; 25 were Turkish Cypriots and 53 were
      Greek Cypriots. Four deletional and three non-deletional alpha-thal alleles were
      present; the -alpha(3.7 kb) alpha-thal-2 and the --MED-I alpha-thal-1 were most
      frequently seen; --MED-II and -(alpha)20.5 deletions occurred at considerably
      lower frequencies. About 15% of all chromosomes carried a non-deletional alpha
      thal-2 allele; of these the 5 nucleotide (nt) deletion at the first intervening
      sequence (IVS-I) donor splice site was present in approximately 8% of all
      chromosomes. Two types of polyadenylation signal (poly A) mutations were
      observed. No striking frequency differences were seen between Greek and Turkish
      Cypriot patients. Combinations of the various types of alpha-thal resulted in
      eight different forms of Hb H disease. The phenotypes were comparable except for
      great variations in the level of Hb H which was highest (average approximately
      22%) in the 12 patients with the alpha 5nt alpha/--MED-I combination. One patient
      with the same form of Hb H disease but with an additional beta-thal (IVS-I-110,G-
      >A) heterozygosity had a most severe microcytosis and hypochromia with < 1% Hb H.
      Variations in the level of Hb H might correlate with the severity of the disease,
      although this was not evident from the haematological data.

PMID- 7734347
TI  - Fatal haemoptysis in pulmonary filamentous mycosis: an underevaluated cause of
      death in patients with acute leukaemia in haematological complete remission. A
      retrospective study and review of the literature. Gimema Infection Program
      (Gruppo Italiano Malattie Ematologiche dell'Adulto)
AB  - A retrospective study on a consecutive series of 116 patients affected by acute
      leukaemia with documented pulmonary filamentous mycosis (FM) admitted between
      1987 and 1992 to 14 tertiary-care hospitals in Italy was made in order to
      evaluate the characteristics of those patients who developed fatal massive
      haemoptysis. In 59/116 cases of pulmonary FM the infection was the principal
      cause of death and in 12 of these patients a massive haemoptysis was responsible
      for death. The diagnosis of FM infection was made ante-mortem in only four out of
      these 12 patients. The autopsy was performed in 11/12 patients and documented a
      FM infection. The mycetes isolated were: Hyphomycetes spp. (three patients),
      Mucorales spp. (two patients), Aspergillus spp. (seven patients). At the time of
      the massive haemoptysis the mean neutrophil count was 7.2 x 10(9)/l, and no
      patient had relevant thrombocytopenia (mean 184 x 10(9)/l, range 28-350) or
      coagulative abnormalities. The mean time which elapsed between resolution of
      chemotherapy-induced neutropenia (WBC < 10(9)/l) and occurrence of haemoptysis
      was 7 d. No signs or symptoms predictive of this fatal complication were
      identified. Massive haemoptysis can be the cause of death in patients with acute
      leukaemia and pulmonary FM which in the majority of patients was not diagnosed in
      vivo. This complication occurs most frequently shortly after the recovery from
      chemotherapy-induced aplasia. The mechanism of lesion is unknown, but it may
      involve the vascular tropism of FM and the release of leucocyte enzymes. Better
      preventive and therapeutic antifungal treatments are needed to avoid this
      serious, albeit rare, complication.

PMID- 7734348
TI  - T-cell-depleted allogeneic bone marrow transplantation for acute leukaemia using
      Campath-1 antibodies and post-transplant administration of donor's peripheral
      blood lymphocytes for prevention of relapse.
AB  - One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with
      ALL) received allogeneic bone marrow transplantation from their fully matched
      siblings. 121 patients underwent T-cell depletion (TCD) using Campath 1
      monoclonal rat anti-human lymphocyte (CDw52) antibodies; 67 with Campath 1M and
      54 with Campath 1G isotypes. Patients were conditioned for transplant using
      either total body irradiation combined with chemotherapy (125 patients) or
      busulfan and cyclophosphamide (21 patients). 112 recipients of T-cell depleted
      allografts received in addition total lymphoid irradiation (TLI) for prevention
      of rejection. Engraftment of neutrophils (> 0.5 x 10(9)/l) and platelets (> 25 x
      10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipients of
      Campath 1M and Campath 1G treated marrows respectively. Rejection was documented
      in 6.8% of T-cell depleted transplants. Leukaemia relapse-free survival at 2
      years was 83% for patients transplanted in first CR, 76% in second CR (P2 = 0.34)
      and 42% in advanced leukaemia (P2 = 0.009). 81 marrow recipients, 38 with Campath
      1M and 43 with Campath 1G treated marrow, received post-transplant graded
      increments of donor's peripheral blood lymphocytes (PBL) to induce graft-versus
      leukaemia (GVL) effects. Administration of donor's PBL was associated with
      clinically significant GVHD and with decreased relapse rate especially in
      patients with ALL. Our data suggest that in patients receiving marrow allografts
      depleted of T cells by Campath 1 monoclonal antibodies, rejection can be reduced
      by adequate pregrafting immunosuppression. In patients with advanced disease,
      post-transplant cell-mediated immunotherapy (CMI) using donor's PBL may be
      beneficial; however, further studies are needed to define the optimal schedule of
      CMI for safe and effective prevention of relapse following TCD bone marrow
      transplantation in malignant haematological diseases.

PMID- 7734349
TI  - Heterogeneity of t(1;19)(q23;p13) acute leukaemias. French Haematological
      Cytology Group.
AB  - The t(1;19)(q23;p13) translocation occurs commonly in B-lineage ALL. Previous
      reports have demonstrated a predominance of cases with expression of cytoplasmic
      Ig mu (C mu+), and FAB L1/L2 phenotype, a poor prognosis and expression of a
      fusion transcript involving the E2A and PBX1 genes in C mu+ but not in C mu-
      cases. Of 38 patients with karyotypically proven t(1;19) (q23;p13) leukaemias, we
      extensively analysed 18 patients with acute leukaemia including 16 B-lineage
      ALLs, one T-ALL and one AML M4. The AML was associated with a classic E2A-PBX1
      fusion transcript and may represent the human counterpart of the AMLs induced by
      E2A-PBX1 retroviral infection of murine marrow progenitors. The T-ALL was E2A
      PBX1 negative and neither the E2A nor the LYL-1 genes, both situated at
      chromosome 19 p13, were rearranged. Of the 16 B-lineage ALLs, four had
      cytological features resembling an 'L3-like' phenotype classically associated
      with Burkitt's lymphoma, two at diagnosis and relapse and two exclusively at
      relapse. E2A-PBX1 fusion transcripts were detected by RT-PCR in all 13 C mu+
      patients and in 2/3 C mu- cases. The 'L3-like' phenotype did not correlate with a
      particular stage of maturation arrest (one sIg+, one C mu+, one C mu-) or type of
      E2A-PBX1 transcript, but was associated in all cases with a trisomy 8.
      Translocation, rearrangement, amplification or over-expression of the c-myc gene
      was not observed in these cases, demonstrating that the apparent association with
      trisomy 8 is not due to deregulation of this gene. We therefore show that the E2A
      PBX1 transcript, although occurring predominantly in C mu+ pre-B ALL, also occurs
      in C mu- early pre-B ALL, sIg+ B-ALL and even in AML. These results suggest that
      the stage of maturation arrest, and indirectly the prognosis, are not solely due
      to the type of fusion transcript associated with the t(1;19).

PMID- 7734350
TI  - Unexpected high incidence of intracranial subdural haematoma during intensive
      chemotherapy for acute myeloid leukaemia with a monoblastic component.
AB  - We report a high incidence of subacute, chronic and sometimes occult intracranial
      subdural haematoma (SDH) occurring during intensive chemotherapy for acute
      myeloid leukaemia (AML) with a monoblastic component. Between March 1990 and
      January 1993, 86 AML patients from our institution were randomized in the
      multicentric French AML 90 trial. Eight patients (9%) presented a grade > 2
      haemorrhagic event, which was intracranial SDH in five of them. All these five
      SDH patients had hyperleucocytic AML4 or AML5 and had experienced at least one
      lumbar puncture (LP) before SDH diagnosis (with intrathecal chemotherapy in four
      cases). SDH diagnosis was assessed on a brain computed tomography scan which was
      performed 1-9 d after initial SDH symptoms (mainly mild headaches considered a
      result of prior LP). All these five patients recovered from this severe event
      after a specified therapy. SDH does not appear to be an uncommon complication of
      AML4 and AML5 therapy. Its incidence might be under-reported because of poor
      symptomatology. Lumbar punctures, known to cause exceptional SDH in nonleukaemic
      patients, might trigger these haemorrhagic events, eventually in combination with
      other predisposing factors such a haemostasis disorders or leukaemic CNS
      infiltration.

PMID- 7734351
TI  - Emergence of karyotypically unrelated clone in remission of de novo acute
      myeloblastic leukaemias.
AB  - Serial cytogenetic analysis revealed karyotypically unrelated clones in four
      patients with acute myeloblastic leukaemia (AML) in remission. At diagnosis,
      three patients had t(8;21)(q22;q22) and one had an inv(16)(p13q22). After 18-22
      months in remission, different clones emerged in each patient with
      myelodysplastic features of the bone marrow cells. The emergence of clones with
      abnormalities of chromosome 7 in remission seems to be an unfavourable factor for
      prognosis.

PMID- 7734352
TI  - Interferon response in chronic myeloid leukaemia correlates with ABL/BCR
      expression: a preliminary study.
AB  - alpha-Interferon (IFN) has been used to induce cytogenetic remission in chronic
      myeloid leukaemia (CML), but there are few indicators to predict IFN response.
      The role of the chimaeric BCR/ABL gene in the malignant process is undisputed.
      There are, however, conflicting views as to whether the breakpoint site within
      the BCR gene, and the type of mRNA produced determine disease prognosis and
      progression. The function and clinical significance of the newly discovered
      ABL/BCR mRNA has not been investigated for a correlation with CML prognosis or
      response to therapy. We have used a two-step reverse transcriptase polymerase
      chain reaction (RT-PCR) to detect the transcripts of the chimaeric genes BCR/ABL,
      ABL/BCR, as well as the normal ABL and BCR genes in 24 CML patients treated with
      IFN. Because of the variable expression of the four transcripts at presentation,
      a correlation between gene expression, prognosis and clinical progression was
      examined. No correlation between prognosis and gene expression was seen. Also, no
      correlation was found between expression of BCR, ABL or BCR/ABL mRNA and response
      to treatment with IFN. However, 7/10 ABL/BCR mRNA positive patients achieved a
      major cytogenetic response to IFN; but of the 13 ABL/BCR mRNA negative patients,
      only two achieved a major cytogenetic response (P = 0.013). Further studies are
      required to confirm these findings.

PMID- 7734353
TI  - Analysis of molecular breakpoint and m-RNA transcripts in a prospective
      randomized trial of interferon in chronic myeloid leukaemia: no correlation with
      clinical features, cytogenetic response, duration of chronic phase, or survival.
AB  - Two hundred and nineteen cases of Ph+ve CML and 15 Ph-ve, BCR+ve CML cases have
      been analysed to determine the breakpoint site and its relationship to clinical
      features, cytogenetic response, duration of chronic phase and survival. 119 cases
      have had RNA analysis performed to determine the type of BCR/ABL transcript and
      have also been analysed in a similar way. Presenting features at diagnosis
      including age, sex, white-cell count and platelet count showed no significant
      difference for those with 5' and 3' breakpoints and those with either b2a2 or
      b3a2 BCR/ABL transcripts. However, in a subgroup of patients whose presenting
      white-cell count was < 100 x 10(9)/l, those with b3a2 transcript did have a
      significantly higher platelet count. Analysis by Sokal risk grouping showed no
      difference for 5' or 3' breakpoints but a trend for lower stage among those with
      b2a2 transcripts. No correlation was found either for genomic breakpoint site or
      BCR/ABL RNA transcript in terms of duration of chronic phase or survival. When
      stratified by randomized therapy, either interferon-alpha or standard
      chemotherapy, no difference was noted in relation to genomic breakpoint site or
      BCR/ABL transcript. Cytogenetic response was not related to the molecular
      findings.

PMID- 7734354
TI  - Retinoic acid inhibits the growth of human myeloma cells in vitro.
AB  - Retinoic acid has been shown to induce growth inhibition in a variety of cell
      types including human myeloma cell lines. Bone marrow plasma cells from 31
      multiple myeloma (MM) patients were cultured to investigate the activity of 13
      cis-retinoic acid (cRA), all-trans-retinoic acid (tRA), interferon-alpha (IFN
      alpha), interferon-gamma (IFN-gamma), and dexamethasone (DEX), alone or in
      combination, on in vitro proliferation and immunoglobulin (Ig) secretion. Both
      cRA and tRA inhibited proliferation: the labelling index (LI) of treated
      cultures/controls, was 0.47 +/- 0.05 (mean +/- standard error mean, M +/- SEM) P
      < 0.0001, and 0.67 +/- 0.04 (M +/- SEM), P < 0.0001, respectively. The inhibitory
      effect of cRA was significantly superior to tRA (P = 0.0129) and IFN-alpha,
      similar to IFN-gamma and DEX. The combinations of cRA + IFN alpha, tRA + IFN
      gamma, tRA + DEX did not show any synergistic effect on myeloma proliferation. In
      contrast, the combination cRA + DEX (0.29 +/- 0.04, M +/- SEM) markedly increased
      the effect of both cRA and DEX used as single agents. Ig synthesis was not
      significantly affected by CRA, tRA, IFN-gamma and the combination tRA + IFN
      gamma. As expected, only IFN-alpha (P = 0.002) and DEX (P < 0.001) inhibited Ig
      production. The combinations cRA + IFN-alpha, cRA + DEX and tRA + DEX decreased
      Ig secretion to the same extent as IFN-alpha and DEX alone respectively. In
      conclusion, our data indicate that tRA and especially cRA strongly inhibited
      plasma cell proliferation but had no effect on Ig synthesis. The combination of
      cRA + DEX showed the highest degree of inhibitory activity of all cytokines,
      alone or in combination.

PMID- 7734355
TI  - Interferon alfa-2b versus no maintenance therapy during the plateau phase in
      multiple myeloma: a randomized study. Cooperative Study Group.
AB  - This clinical trial was designed to investigate if maintenance therapy with alfa
      interferon could prolong the plateau phase in patients with multiple myeloma. In
      addition, the tolerability of interferon treatment and its effect on survival
      were evaluated. From September 1987 to September 1989 a total of 314 patients
      were accrued to a multi-institutional randomized clinical trial. All patients
      entered into the protocol received standard melphalan-prednisone (MP) induction
      therapy. Response was noted in 184 (59%) and a plateau phase achieved in 155
      (49%). From the latter group, 125 eligible patients were randomized to either
      interferon alfa-2b or no maintenance. The patients were followed for an average
      of 51 months (minimum 36 months) from the time of randomization. The plateau
      phase was significantly prolonged in the group of patients treated with
      interferon (median 13.9 v 5.7 months from the time of randomization; P < 0.0001).
      The interferon therapy was tolerated fairly well, moderate granulocytopenia and a
      chronic fatigue syndrome being the most frequent side-effects (22% v 18% W.H.O.
      grade 3 toxicity). The median survival from randomization was almost identical in
      both groups (36 v 35 months). The study shows that interferon maintenance therapy
      given to multiple myeloma patients who have achieved a response to initial
      treatment with MP prolongs the plateau phase duration with tolerable toxicity.
      The clinical value of this finding should be interpreted with caution, because
      survival was not prolonged. Further studies are required to clarify the role of
      interferon in the treatment of multiple myeloma.

PMID- 7734356
TI  - Frequent association of t(3;14) or variant with other lymphoma-specific
      translocations.
AB  - Malignant lymphomas (ML) with t(3;14) or variant t(2;3) and t(3;22) have recently
      been recognized. These translocations have been shown to associate predominantly
      with B-cell diffuse large cell lymphoma (DLCL) and less frequently with
      follicular lymphoma (FL). The molecular alterations associated with these
      translocations involve one of the immunoglobulin gene (Ig) loci and a recently
      cloned gene, bcl-6 located at 3q27 which codes for a zinc-finger protein that may
      function as a transcription factor. We have identified by cytogenetic analysis 22
      cases of ML with a 3q27/Ig translocation. The pathologic diagnoses of these cases
      include DLCL, FL, small non-cleaved non-Burkitt lymphoma and chronic lymphocytic
      leukaemia. Molecular analysis confirmed a bcl-6 rearrangement in 10/12 cases
      tested. The karyotype in 5/22 cases revealed the t(3;14) or variant in
      association with another lymphoma-specific translocation, t(14;18) in three cases
      and t(8;14) in two cases. ML with dual translocations that implicate Ig genes in
      the deregulation of proto-oncogenes are being increasingly recognized and may
      represent distinct subtypes or 'hybrid' forms of malignant lymphoma.

PMID- 7734357
TI  - The receptor for urokinase plasminogen activator is present in plasma from
      healthy donors and elevated in patients with paroxysmal nocturnal
      haemoglobinuria.
AB  - The urokinase plasminogen activator (uPA) is a proteolytic enzyme which converts
      the proenzyme plasminogen to the active serine protease plasmin. A cell surface
      receptor for uPA (uPAR) is attached to the cell membrane by a glycosyl
      phosphatidylinositol anchor. Binding of uPA to uPAR leads to an enhanced plasmin
      formation and thereby an amplification of pericellular proteolysis. We have shown
      previously that uPAR is expressed on normal blood monocytes and granulocytes, but
      is deficient on affected blood monocytes and granulocytes in patients with
      paroxysmal nocturnal haemoglobinuria (PNH), and that uPAR is present in plasma
      from these patients. In this study a newly established sensitive enzyme-linked
      immunosorbent assay (ELISA) has been applied for quantitation of uPAR in plasma.
      Unexpectedly, we found that uPAR is not only present in PNH plasma but also in
      plasma from healthy individuals. In 39 healthy individuals the mean plasma-uPAR
      value +/- SD was 31 +/- 15 pM, median 28 (range 11-108), and the corresponding
      value for six PNH patients was 116 +/- 67 pM, median 90 (range 61-228). The
      elevated uPAR-level in PNH patients was highly significant (Mann-Whitney test; P
      < 0.0001), and may possibly contribute to the propensity for thrombosis in PNH by
      inhibition of the fibrinolytic system. Binding of pro-uPA by uPAR in plasma may
      interfere with the appropriate binding of pro-uPA to cell-bound uPAR and
      therefore inhibit cell-associated plasmin generation and fibrinolysis. It is
      likely that the uPAR in normal plasma reflects the overall level of activity of
      the uPAR-mediated cell surface proteolysis. The present ELISA may be used for
      studies of uPAR levels in plasma from patients with conditions in which this
      activity might be increased, such as cancer and inflammatory disorders. Future
      studies will determine if uPAR in plasma is a parameter of clinical importance in
      these diseases.

PMID- 7734358
TI  - Attenuated platelet sensitivity to collagen in patients with neurofibromatosis
      type 1.
AB  - Haemostatis has not previously been studied in patients with neurofibromatosis 1
      (NF-1), despite case reports of an association with von Willebrand disease and
      reported excessive bleeding in those undergoing surgery for neurofibromas.
      Platelets from NF-1 patients (n = 28) were tested for aggregation and ATP release
      with agonists including ADP, arachidonic acid, thrombin and collagen. Mepacrine
      staining of platelets and three different assays for von Willebrand factor (VWF)
      were also performed. In response to collagen as the platelet agonist, tested at
      both 2 and 1 micrograms/ml, NF-1 patients had an attenuated rate of aggregation
      (P < 0.007), aggregation lag phase (P < 0.005) and ATP release (P < 0.045), as
      well as requiring higher collagen concentrations to attain threshold aggregation
      response (P = 0.041). Normal platelets resuspended in selected NF-1 plasma
      exhibited significantly reduced platelet aggregation and release compared to
      controls, which was not corrected by mixing 1:1 with normal plasma. Collagen
      binding activity was reduced in NF-1 patients compared with controls (127% v
      161%, P = 0.05). As a group, patients with NF-1 display defective platelet
      function characterized by in vitro evidence of impaired responsiveness to
      collagen. It is suggested that a plasma factor, present in a significant
      proportion of NF-1 patients, may interfere with the ability of collagen to
      interact with other proteins such as von Willebrand factor and the platelet
      collagen receptor.

PMID- 7734359
TI  - Antithrombin-TRI (Ala382 to Thr) causing severe thromboembolic tendency undergoes
      the S-to-R transition and is associated with a plasma-inactive high-molecular
      weight complex of aggregated antithrombin.
AB  - An antithrombin (AT) variant Ala382 to Thr (AT-TRI) was identified by mass
      spectrometric techniques. The variant behaved as a substrate rather than a
      thrombin inhibitor, but, contrary to previously described P12 AT variants, AT
      TRI, expressed as a heterozygous dominant trait, caused severe thromboembolic
      tendency beginning in their teens in affected members of an English family. In
      addition, it underwent the S-to-R conformational state transition as evidenced by
      an increased resistance to thermal denaturation on active centre cleavage, but
      did not react with a monoclonal antibody, 4C9, directed against a neoepitope that
      is present on complexed and cleaved normal AT. Antithrombin-TRI, in plasma, was
      also associated with an abnormal high molecular weight (M(r)) 194,000) component
      composed of non-covalently-linked antithrombin molecules. This component (D194)
      showed low affinity for heparin and was devoid of antithrombin progressive
      activity. D194, isolated by ammonium sulphate precipitation and three
      chromatographic steps (heparin Sepharose, ion exchange and immunoaffinity),
      migrated as a single band of M(r) 60,000 on SDS-PAGE under both reducing and non
      reducing conditions and was recognized by monospecific anti-human antithrombin
      antibodies, but did not immunoreact with antibodies raised against a number of
      proteins including albumin and thrombin. The above data and the fact that the 15
      N-terminal amino acids of this M(r) 60,000 band were identical to that of normal
      antithrombin indicated that the inactive D194 component was composed of
      aggregated antithrombin molecules, possibly antithrombin trimers. In conclusion,
      early adulthood severe thromboembolic tendency, failure to expose the 4C9
      epitope, and presence of aggregated AT molecules in the plasma are characteristic
      features of AT-TRI not previously described in other ALA-382 THR mutations.

PMID- 7734360
TI  - Antithrombins Southport (Leu 99 to Val) and Vienna (Gln 118 to Pro): two novel
      antithrombin variants with abnormal heparin binding.
AB  - We report the characterization of three variant antithrombins with reduced
      heparin binding as the primary abnormality. Two of these variants, antithrombin
      Southport (Leu 99 to Val, 2759 C to G) and antithrombin Vienna (Gln 118 to Pro,
      5349 A to C) were novel, whereas the third, Pro 41 to Leu, has been previously
      described as antithrombin Basel. All three variants exhibited reduced binding for
      heparin on crossed immunoelectrophoresis and in a quantitative monoclonal
      antibody-based assay. The mutations were characterized by direct sequence
      analysis of enzymatically amplified genomic DNA and all affected individuals were
      heterozygous for the mutations. These three mutations do not occur at the sites
      of the basic amino acids directly involved in heparin binding nor do they result
      in a change in charge of the affected residue. It seems probable that they reduce
      heparin affinity either by perturbing the initial contact site involved in the
      heparin-binding domain (Arg 47, Arg 129 and possibly Arg 24), or by preventing
      the subsequent heparin-induced conformational change.

PMID- 7734361
TI  - Severe autoimmune protein S deficiency in a boy with idiopathic purpura
      fulminans.
AB  - Idiopathic purpura fulminans usually occurs in young children and is frequently
      preceded by a preparatory viral or bacterial infection. Following a severe
      streptococcal pharyngitis, an 8-year-old boy developed purpura fulminans with
      disseminated intravascular coagulation and severe protein S deficiency (total
      antigen < 0.05 u/ml). Despite generous plasma infusions, skin necrosis progressed
      rapidly into compartment syndrome which required fasciotomy and skin grafting and
      resulted in the loss of three digits of the right foot. Total protein S remained
      low for over a month despite plasma supplementation and complete normalization of
      protein C levels. A polyclonal anti-protein S IgG was demonstrated in the
      patient's plasma, which decreased to 25% of baseline titre after 1 month and was
      undetectable 6 months after purpura fulminans, when plasma protein S had returned
      to normal. Transient, isolated and severe deficiencies of protein S have been
      reported in patients with idiopathic purpura fulminans and a previous preparatory
      infection. Autoimmune protein S deficiency may play a key role in the
      aetiopathogenesis of idiopathic purpura fulminans.

PMID- 7734362
TI  - The first report of familial adult T-cell leukaemia lymphoma in the United
      Kingdom.
AB  - We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL)
      within 4 years. Both were black of Afro-Caribbean extraction, but one had been
      born in the United Kingdom and had visited the Caribbean only once. Both patients
      were HTLV-1 seropositive, as was their mother; their father and brother were
      negative. The older sibling had the lymphoma form of ATLL, whilst the younger had
      chronic ATLL. The former was unresponsive to chemotherapy and died of progressive
      disease; the latter experienced transient responses to various treatments and is
      alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+
      phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the
      tissues involved. This report, of the first familial ATLL in the U.K., supports
      the suggestion of transmission of HTLV-I from mother to child and documents the
      development of ATLL in second-generation Caribbean immigrants.

PMID- 7734363
TI  - Expression of granulocyte colony-stimulating factor receptor on CD10-positive
      human B-cell precursors.
AB  - We examined the expression of CD10 and G-CSF receptor (G-CSFR) on the lymphoid
      population of mononuclear cells obtained from bone marrow (BM) using two-colour
      analysis. In the BM of children with ALL in remission, the CD10+ population was
      significantly increased (20.6 +/- 5.1% compared with that of controls (2.5 +/-
      0.5%). More than half (61.3 +/- 2.9%) of the CD10+ cells co-expressed G-CSFR, but
      not CD13. These results indicate G-CSFR+ B-cell precursors are markedly increased
      in BM of ALL in remission, suggesting the probable involvement of G-CSF in the
      human early B-cell ontogeny.

PMID- 7734364
TI  - Effective treatment of disease-related anaemia in B-chronic lymphocytic leukaemia
      patients with recombinant human erythropoietin.
AB  - Nine B-chronic lymphocytic leukaemia (B-CLL) patients suffering from anaemia, due
      to no obvious cause except their disease, were treated with recombinant human
      erythropoietin (r-HuEPO). The treatment protocol provided a closed label phase of
      3 months duration, during which the patients received r-HuEPO or placebo in a
      ratio of 2:1, followed by an open label phase, also of 3 months duration, during
      which r-HuEPO was administered to all patients three times a week s.c. r-HuEPO
      was given a dose of 150 U/kg of body weight with an escalation of 50 U/kg up to a
      maximum of 300 U/kg three times a week. Complete response was achieved in 5/9
      (55%) patients and partial response in 3/9 (33%). The response obtained was
      independent of the pretreatment serum EPO levels, the duration of anaemia, the
      concomitant administration of chemotherapy, the presence of splenomegaly, or the
      degree of bone marrow infiltration by lymphocytes. It appears that r-HuEPO is
      very effective in reversing the disease-related anaemia of B-CLL patients.

PMID- 7734365
TI  - Epinephrine test and plasma elastase as diagnostic tools in a patient with CD3+
      large granular lymphocyte proliferation.
AB  - Large granular lymphocytes (LGL) proliferation is characterized by expansion of
      cytotoxic lymphocytes and associated with neutropenia. In a case of CD3+ LGL
      proliferation the epinephrine stimulation test (EST) induced a striking elevation
      of CD3+, CD8+, CD57+ LGL in peripheral blood from 2.7 x 10(9)/l to 20 x 10(9)/l
      and might be an additional diagnostic tool in patients with normal or low
      absolute numbers of circulating LGL. After treatment with steroids, plasma
      elastase--a marker of neutrophil destruction--decreased from 162 to 40
      micrograms/l (normal < 47 micrograms/l) which correlated well with a simultaneous
      increase in peripheral neutrophil counts from 0.14 to 1.0 x 10(9)/l. This finding
      supports the hypothesis that neutropenia in CD3+ LGL proliferation is due to
      neutrophil destruction, possibly mediated by LGL.

PMID- 7734366
TI  - Non-radioactive SSCP for genotyping human platelet alloantigens.
AB  - Human platelet alloantigen systems are responsible for neonatal and post
      transfusional thrombocytopenias. The determination of the different allotypes can
      be performed using immunological or DNA-based methods. The most used DNA-based
      procedure requires the digestion by specific restriction enzymes of PCR products
      containing the genetic determinants of these alloantigens. We now report a rapid
      method of genotyping which does not use restriction enzymes and is less prone to
      misinterpretation. This is non-radioactive PCR-SSCP (single strand conformation
      polymorphism), which we illustrate for two different HPA systems, one on GPIIIa
      (HPA-1) and the other on GPIIb (HPA-3).

PMID- 7734367
TI  - Low-dose cladribine for symptomatic hairy cell leukaemia.
AB  - Cladribine is an effective therapy for hairy cell leukaemia (HCL), but the
      standard regime is frequently complicated by neutropenic fever and prolonged T
      cell depression. We studied 102 patients with active HCL following treatment with
      various doses of cladribine given for 7 d. Two patients received 1 mg
      cladribine/m2/d without toxicity or effect. Eight subsequent patients received 2
      mg cladribine/m2/d, and normalized cytopenia as quickly as 94 control patients
      receiving a standard dose (3.4 mg/m2 or 0.085 mg/kg), with significantly less
      lymphopenia and a similar complete remission rate.

PMID- 7734368
TI  - Detection of monoclonal plasma cells in the peripheral blood stem cell harvests
      of patients with multiple myeloma.
AB  - We evaluated the harvest product from 47 patients undergoing peripheral blood
      (BP) stem cell collections for monoclonal plasma cells (PC) using a sensitive
      immunofluorescence technique. 60% (28/47) had documented tumour cells in the
      apheresis product. The 32 patients in plateau had a mean of 1.62 x 10(6) PC/l v
      74.64 x 10(6) in 15 relapsed patients (P < 0.01). 32% (6/19) of patients without
      any tumour cells in the initial sample had them detected on a subsequent
      apheresis sample. In four cases (all treated with GM-CSF) small numbers of tumour
      cells were detected initially but became undetectable on a subsequent sample.

PMID- 7734369
TI  - Thrombotic thrombocytopenic purpura-like syndrome in the absence of schistocytes.
AB  - Thrombotic thrombocytopenic purpura is an uncommon disorder that if left
      untreated has a very high mortality. Schistocytes are generally considered
      essential for the diagnosis. A patient is presented with a thrombotic
      thrombocytopenic purpura-like syndrome in whom schistocytes were persistently
      absent and who responded to plasmapheresis.

PMID- 7734370
TI  - Application of a polymorphic Y microsatellite to the detection of post bone
      marrow transplantation chimaerism.
AB  - A highly sensitive Y-microsatellite amplification system was developed for the
      detection of post bone marrow transplantation (BMT) chimaerism. The system is
      able to detect the DNA equivalent of a single male cell in a background of 10(5)
      female cells. For clinical applications it has the distinct advantage that the
      polymorphic nature of the PCR product allows the checking of the genuineness of a
      positive PCR signal by reference to its allelic type. This extra degree of
      precision enhances the accuracy of Y-PCR for clinical diagnosis.

PMID- 7734371
TI  - Transformation into acute basophilic leukaemia in a patient with myelodysplastic
      syndrome.
AB  - We describe a patient with basophilic leukaemia following a 2-year period with
      myelodysplastic syndrome (refractory anaemia). The marrow showed 59.4% of blasts
      with 25.0% of mature and immature basophils. The leukaemic blasts contained
      granules, positively stained with toluidine blue but negative for peroxidase. The
      basophilic differentiation was confirmed by ultrastructural analysis
      demonstrating immature basophil granules. In addition, a morphological transition
      from immature blasts to more mature basophils was observed. Immunophenotypic
      analysis of blasts and basophils showed positive for CD5, CD7, CD13, CD33 and
      CD34. Cytogenetic investigation showed an abnormal karyotype,
      46,XY,del(5)(q31q35), in 11% of the cells examined when the initial diagnosis of
      refractory anaemia was made. However, expansion of the same clone up to 100% was
      observed concomitantly with transformation to basophilic leukaemia.

PMID- 7734372
TI  - Persistent lymphocytosis of natural killer cells in autoimmune thrombocytopenic
      purpura (ATP) patients after splenectomy.
AB  - We report three patients with primary autoimmune thrombocytopenic purpura (ATP)
      who developed an absolute lymphocytosis (lymphocyte count > 5 x 10(9)/l) after
      splenectomy and with a lymphocyte count between 5.4 and 8.9 x 10(9)/l. An
      immunophenotype study showed that the peripheral blood lymphocytosis was a
      persistent NK cell expansion (CD2+, CD56+, CD3-), and was characterized by a
      typical large granular lymphocytes (LGL) morphology. Two of these three ATP
      patients were refractory to splenectomy.

PMID- 7734373
TI  - A novel candidate mutation (Arg611-->His) in type I 'platelet discordant' von
      Willebrand's disease with desmopressin-induced thrombocytopenia.
AB  - In three affected members of a family with type I 'platelet discordant' von
      Willebrand's disease displaying desmopressin-induced thrombocytopenia, we have
      detected in exon 28 of the von Willebrand factor gene a heterozygous G(4121)-->A
      transition, which predicts an Arg611-->His substitution. The mutated allele was
      absent in 50 normal individuals. An unrelated patient with a similar phenotype
      was also found to be heterozygous for this mutation. The mutation is located in
      the A1 domain of von Willebrand factor, where most type 2B von Willebrand's
      disease mutations are found. Mutations in this domain result in von Willebrand
      factor multimers with enhanced affinity for platelet glycoprotein Ib, and this
      may explain the association of Arg611-->His with the moderate thrombocytopenia
      observed after desmopressin infusion.

PMID- 7734374
TI  - Co-segregation of thrombosis with the factor V Q506 mutation in an extended
      family with resistance to activated protein C.
AB  - The activated protein C (APC) resistance phenotype results from a mutation at one
      of the cleavage sites of factor V by APC (Q506). We describe a large family with
      an APC resistance phenotype and without any other detectable coagulation defect,
      including eight subjects who had developed deep venous thrombosis (mean age of
      the first thrombosis episode 29 years; range 17-55 years). The factor V Q506
      mutation was detected in the seven patients with thrombosis who could be tested
      and in 13 asymptomatic subjects (mean age 17 years; range 5-33 years). The APC
      resistance was detectable in only 10 heterozygotes among the 19 tested. These
      data suggest that, in affected families, the risk for the factor V Q506 mutation
      carriers to develop thrombosis may be very high and that factor V genotyping must
      be performed in patients with thrombosis even without any detectable APC
      resistance phenotype.

PMID- 7734375
TI  - Microscopic haematuria as a relative contraindication for tranexamic acid.
AB  - Tranexamic acid has been advocated for patients with severe bleeding tendency due
      to thrombocytopenia not responding to platelet transfusions. Macroscopic
      haematuria is a well-known contraindication for its use in such patients. We
      present three clinical cases with microscopic haematuria, in whom tranexamic acid
      caused problems of clot formation in the urinary tract, indicating that
      microscopic haematuria should also be considered as a contraindication for
      tranexamic acid.

PMID- 7734376
TI  - Detection of chromosome 11 alterations in blood and bone marrow by interphase
      cytogenetics in mantle cell lymphoma.
AB  - The t(11;14)(q13;q32) translocation is a consistent chromosome change in mantle
      cell lymphomas. This study investigates the application of fluorescent in situ
      hybridization (FISH) with chromosome painting probes for interphase cytogenetic
      analysis in patients with mantle cell lymphomas. Chromosome 11 paints have been
      able to show splitting of the chromosome signal consistent with the t(11;14)
      translocation in interphase cells from bone marrow and blood of patients with
      mantle cell lymphomas. These include some in clinical remission. The chromosome
      probes conjugated with fluorescent molecules are hybridized with patient's DNA
      allowing the easy detection of chromosome 11 abnormalities with fluorescent-light
      microscopes. Interphase FISH has a higher sensitivity and is quicker than
      standard metaphase cytogenetics. This may be beneficial in rapid detection of
      chromosome 11 abnormalities, assisting in the diagnosis of mantle cell lymphomas.
      In addition, detection of a clonal population of cells is possible.

PMID- 7734377
TI  - Identification of biclonal (duplex) leukaemic cells expressing either CD4+/CD8-
      or CD4-/CD8+ from a patient with adult T-cell leukaemia/lymphoma.
AB  - A 24-year-old Japanese woman was admitted to our hospital in 1987 with a chief
      complaint of skin eruptions, and was diagnosed as having chronic ATLL. In 1993
      the leucocyte count increased gradually to 126.0 x 10(9)/l with 91.5% abnormal
      lymphocytes expressing two different types of antigenicity, either CD+/CD8- or
      CD4-/CD8+. Monoclonal integration of human T-cell lymphotropic virus type-I
      proviral DNA was detected at different sites of the genomic DNA in each cell
      type. These studies clearly indicate that CD4+/CD8- and CD4-/CD8+ leukaemic cells
      originated from two independent clones.

PMID- 7734378
TI  - The high frequency of the -6G-->A factor IX promoter mutation is the result both
      of a founder effect and recurrent mutation at a CpG dinucleotide.
AB  - We report a new Liverpool family with a mild haemophilia B Leyden phenotype
      caused by a -6G-->A mutation in a CpG dinucleotide in the promoter of the
      clotting factor IX gene. This mutation had previously been identified in three
      other U.K. pedigrees and six others worldwide. To investigate whether these
      mutations were of independent origin, the haplotype was determined for eight
      polymorphic loci, within or immediately adjacent to the factor IX gene, for nine
      of the 10 existing patients. Six probands had identical haplotypes, including all
      four U.K. probands, suggesting that they arose from a common founder. The other
      three probands differed in haplotype from the common haplotype, and from each
      other, suggesting that they were independent mutations at this CpG dinucleotide.

PMID- 7734379
TI  - Refractory anaemia with preleukaemic polyclonal haemopoiesis and the emergence of
      monoclonal erythropoiesis on disease progression.
AB  - We describe a young woman with a myelodysplastic syndrome (MDS) of the type
      refractory anaemia (RA) which remained stable for 11 years and then underwent
      rapid progression manifested by bone marrow failure with the emergence of a
      complex clonal cytogenetic abnormality. Peripheral blood granulocytes,
      mononuclear cells and bone marrow erythroblasts were all polyclonal by X
      inactivation analysis detected by the probe M27B during the preleukaemic phase.
      On disease progression, bone marrow erythroblasts developed an extremely skewed
      monoclonal pattern of X-inactivation. In some cases of MDS, therefore, polyclonal
      haemopoiesis can be detected for a considerable time during the preleukaemic
      phase and we report the demonstration of bone marrow erythroblasts changing from
      a polyclonal to a monoclonal pattern on disease progression.

PMID- 7734380
TI  - In vivo folic acid supplementation partially corrects in vitro methotrexate
      toxicity in patients with Down syndrome.
AB  - Patients with Down syndrome have been found to have characteristic in vivo and in
      vitro methotrexate toxicity. The in vitro methotrexate toxicity characteristic of
      Down syndrome can be diminished by the in vivo administration of supplemental
      high doses of folic acid. A possible explanation for the increased sensitivity to
      methotrexate which has been documented in patients with Down syndrome may be due
      to imbalances in nucleotide pools which result from a gene dosage effect and to
      greater methylation demands. Supplemental folic acid may be beneficial by virtue
      of a down-regulation of excess gene activity and may also provide needed
      monocarbons.

PMID- 7734381
TI  - Evidence of clonality in a child with haemophagocytic lymphohistiocytosis.
AB  - DNA from the bone marrow of a child with haemophagocytic lymphohistiocytosis was
      examined by polymerase chain reaction for evidence of rearrangement of the T-cell
      receptor delta chain gene. Evidence of clonal rearrangement was detected,
      supporting a role for abnormalities of T-cell function in the pathogenesis of
      this disorder.

PMID- 7734382
TI  - International normalized ratio in the control of oral anticoagulant therapy.

PMID- 7734383
TI  - Experiences with the determination of chimaera bcr-abl messages in bone marrow
      and peripheral blood samples in chronic myeloid leukaemia.

PMID- 7734384
TI  - Parathyroid hormone related protein in hypercalcaemia in CLL.

PMID- 7734385
TI  - Abnormal lipoprotein in cholestasis.

PMID- 7734386
TI  - Relation between spiculated red cells and platelets in uraemic patients.

PMID- 7734387
TI  - An interstitial deletion in the rearranged T-cell receptor gamma chain locus in a
      case of T-cell acute lymphoblastic leukaemia.

PMID- 7734388
TI  - Transmission of human T-lymphotrophic virus type 1 by bone marrow
      transplantation.

PMID- 7734389
TI  - Family history and inherited thrombophilia.

PMID- 7734390
TI  - The role of the BR-C locus on the expression of genes located at the ecdysone
      regulated 3C puff of Drosophila melanogaster.
AB  - During the third larval instar, the steroid moulting hormone ecdysone activates
      three temporally distinct puff sets on the D. melanogaster salivary gland
      polytene chromosome: the so-called intermoult, early and late puffs. Hormonal
      regulation of intermoult puffs is quite complex and, so far, largely not
      understood. In order to further investigate this aspect, we have analysed the
      effects of mutations in a key regulator of the ecdysone response at the onset of
      metamorphosis, the Broad-Complex (BR-C) locus, on the expression of genes mapping
      at the 3C intermoult puff. On the basis of an accurate examination of 3C
      intermoult gene activity in single, carefully staged, third instar larvae of wild
      type and BR-C mutant strains, we were able to subdivide these genes into two
      groups. Each group is characterised by a different temporal expression profile,
      so that at the beginning of the wandering stage the transcription of the first
      group declines as group II transcription is induced. Interestingly, the BR-C
      locus appears to play a regulatory role in establishing this transcriptional
      switch. By using mutants of each of the three lethal complementation groups, we
      precisely defined the role of BR-C functions in this developmental transition and
      we show that this locus also plays an essential role in the early pre-metamorphic
      hormonal response.

PMID- 7734391
TI  - Drosophila eye development: Notch and Delta amplify a neurogenic pattern
      conferred on the morphogenetic furrow by scabrous.
AB  - Loss of function mutations of scabrous and conditional alleles of Notch and Delta
      affect the pattern of morphogenetic furrow development. By studying
      differentiation of R8 cells, the first photoreceptor neuron subtype to
      differentiate, we show that all furrow cells pass through an R8-competent stage.
      Function of Notch and scabrous is necessary if most of these cells are to attain
      other cell fates. The scabrous gene confers a regular pattern on the
      morphogenetic furrow, restricting R8 differentiation to alternating groups of
      cells. Notch and Delta function to restrict the R8 fate to a single cell in each
      group. Without scabrous gene function, action of Notch and Delta on the entire
      morphogenetic furrow results in a disorganised pattern of ommatidia arising from
      a disorganised array of single R8 cells. Aspects of the scabrous mutant phenotype
      also suggest a secondary role in selecting a single R8 cell from competent
      clusters. We show that scabrous expression preceeds changes in the apical
      profiles of morphogenetic furrow cells that identify ommatidial precurf1p4cells,
      and also preceeds changes in levels of Notch and Delta expression. The pattern of
      initiation of sca expression depends on sca gene function, indicating that
      patterning of the morphogenetic furrow depends on the pattern of posterior
      columns. Our results suggest that in the eye, Notch and Delta amplify and refine
      a morphogenetic landscape generated by scabrous. Cell determination in other
      tissues and organisms might also be molded in a two-step process where initial
      inhomogeneities determined by one protein provide a context for subsequent
      development.

PMID- 7734392
TI  - Localization and functions of protein kinase A during Drosophila oogenesis.
AB  - We have characterized the requirements for the Protein Kinase A (PKA) catalytic
      subunit, DC0, in Drosophila oogenesis. Intercellular bridges in egg chambers from
      PKA deficient females are unstable, leading to the formation of multinucleate
      nurse cells by fusions of adjacent cells. Germline clones of cells homozygous for
      null mutations of DC0 indicate that PKA acts autonomously in the germline.
      Highest levels of PKA catalytic subunit protein are associated with germ cell
      membranes, suggesting that targets of PKA are associated with the membrane or
      membrane skeleton and contribute to the stabilization of intercellular bridges.
      The migration of a subset of follicle cells, the border cells, is also disrupted
      by germline PKA mutations, implying that nurse cell junctions provide an
      essential path for border cell migrations.

PMID- 7734393
TI  - Effects of the TWis mutation on notochord formation and mesodermal patterning.
AB  - The mouse T (Brachyury) gene is required for early mesodermal patterning. Mice
      homozygous for mutations in T die at midgestation and display defects in
      mesodermal tissues such as the notochord, the allantois and the somitic mesoderm.
      To examine the role of T in patterning of somitic and posterior mesoderm along
      the anterior-posterior axis, we have examined the expression of a panel of
      molecular markers normally localized to the sub-set of cell types affected in
      TWis mutant mice. Through the use of whole-mount antibody double labelling
      techniques, we have analysed the spatial relationships of distinct mesodermal
      populations relative to cells expressing the T protein. We have also examined the
      consequences of the TWis mutation on mesodermal populations recognised by these
      markers. We demonstrate that TWis homozygous mutants retain the ability to form
      notochordal precursor cells, as identified both by the T antibody and the
      expression of sonic hedgehog/vertebrate homolog of hedgehog 1 (Shh/vhh-1) and
      goosecoid, however, these cells fail to proliferate or differentiate. These early
      notochordal defects appear to result in aberrant somitic differentiation as
      revealed by the distribution of mox-1 protein and twist RNA expression. Moreover,
      twist expression in paraxial mesoderm appears to be dependent on normal T
      activity, while Shh/vhh-1, goosecoid, mox-1 and cdx-4 are not T dependent. We
      propose that T is required for the maintenance of notochordal tissue and
      subsequent signals required for somite differentiation.

PMID- 7734394
TI  - XIdx, a dominant negative regulator of bHLH function in early Xenopus embryos.
AB  - We have identified a divergent member of the Xenopus Id family, XIdx, which
      disrupts binding of myogenic factor/E-protein complexes to DNA in vitro and
      inhibits transactivation of the E-box regulated cardiac actin gene by MyoD in
      embryonic tissue. XIdx transcripts accumulate from the early neurula stage in
      discrete domains of the anterior neural plate and subsequently identify regions
      of the developing nervous system, including the eye rudiments and the
      rhombencephalon. These results suggest that bHLH proteins and their Id protein
      regulators may participate in patterning of embryonic neural tissue. Phylogenetic
      analysis indicates that XIdx is the product of a novel Id gene and is distinct
      from XId2, which is expressed primarily in the developing pronephros.

PMID- 7734395
TI  - Zebrafish Radar: a new member of the TGF-beta superfamily defines dorsal regions
      of the neural plate and the embryonic retina.
AB  - Proper development of metazoan embryos requires cell to cell communications. In
      many instances, these communications involve diffusible molecules, particularly
      members of the Transforming Growth Factor beta superfamily. In an effort to
      identify new members of this superfamily involved in the control of early
      zebrafish embryogenesis, we have isolated a gene, Radar, which appears to be
      conserved throughout vertebrate evolution and defines a new subfamily within the
      superfamily. Its pattern of expression suggests that Radar plays a role in the
      dorso-ventral polarity of the neural plate, blood islands formation, blood cells
      differentiation, the establishment of retinal dorso-ventral polarity and/or
      proper axonal retinotectal projections. Radar expression in ntl homozygous
      mutants indicates that notochord and hypochord development are intimately linked.

PMID- 7734396
TI  - Forward to the past! Or, back to proteins.

PMID- 7734397
TI  - Estradiol stimulates c-myc proto-oncogene expression in normal human breast
      epithelial cells in culture.
AB  - The proto-oncogene c-myc is involved in the stimulation of cell proliferation,
      and its expression is known to be stimulated by estradiol (E2) in human breast
      cancer cell lines and various non-cancerous E2-dependent tissues. However, little
      information is currently available concerning its expression and regulation in
      normal human breast tissue. We therefore studied c-myc expression and hormone
      modulation in normal human breast epithelial (HBE) cells in culture, routinely
      obtained in our laboratory and which remain hormone-dependent. On these normal
      HBE cells, E2 induced a biphasic increase in c-myc mRNA level, with a first peak
      as early as 30 min, and a secondary increase after 2 h of treatment; this
      stimulation was dose-dependent, with an optimal concentration of 10 nM E2. Its
      primary action is probably at the transcriptional level since the half-life of c
      myc mRNA measured in the presence of actinomycin D (12 +/- 3 min) was not
      modified by E2 treatment. In addition, E2 stimulation of c-myc mRNA does not
      require protein synthesis since it was not suppressed by cycloheximide treatment.
      Western blot studies of c-myc protein in HBE cells revealed the same biphasic
      pattern of stimulation, with a first peak after 60 min and a second one after 2 h
      of E2 treatment. In conclusion, the c-myc proto-oncogene is expressed in normal
      HBE cells, as in breast cancer cells. Moreover, E2 stimulates c-myc expression
      which, therefore, may partly mediate the growth-promoting effect of E2.

PMID- 7734399
TI  - Retinoids modulate the binding capacity of the glucocorticoid receptor and its
      translocation from cytosol to nucleus in liver cells.
AB  - The binding capacity (Cmax) of the glucocorticoid hormone receptor (GR) was
      affected by vitamin A status in rat liver. In rats fed on a vitamin A-overloaded
      diet as well as in rats administered with retinoic acid (RA) there was an
      increased ratio Cmax of nuclear GR (expressed as fmol/mg liver): Cmax of
      cytosolic GR (expressed as fmol/mg liver) while in rats fed on a vitamin A
      deficient diet this ratio was decreased. These results suggested that an
      increased amount of RA, resulting from either metabolization of an increased
      amount of dietary retinol or RA administration, enhanced the translocation of GR
      from the cytosolic compartment to the nuclear compartment. Moreover such an
      increased amount of RA could also induce the observed decreased Cmax of the total
      GR that we observed. These observations were similar to the well known effects of
      dexamethasone administration on the properties of GR. It is probable that RA,
      similarly to dexamethasone treatment, induces a dissociation of the tetrameric
      form of the cytosolic GR and thus enhances translocation of the monomeric form
      from cytosol to nucleus and also resulting in an increased proteolytic
      degradation of the receptor.

PMID- 7734398
TI  - Cloning, expression and functional characterization of type 1 and type 2 steroid
      5 alpha-reductases from Cynomolgus monkey: comparisons with human and rat
      isoenzymes.
AB  - The Cynomolgus monkey may provide an alternative pharmacological model in which
      to evaluate the efficacy of novel inhibitors of the two known human steroid 5
      alpha-reductase (SR) isoenzymes. To evaluate the suitability of this species at
      the level of the molecular targets, a Cynomolgus monkey prostate cDNA library was
      prepared and screened using human SR type 1 and 2 cDNAs as hybridization probes.
      Two distinct cDNA sequences were isolated encoding the monkey type 1 and 2 SR
      isoenzymes. These sequences share 93 and 95% amino acid sequence identity with
      their human enzyme counterparts, respectively. Difference in monkey type 1 SR,
      however, was found within the contiguous four amino acids corresponding to the
      regions in the human and rat sequences that have been proposed previously to
      influence steroid and inhibitor affinities. Subsequently, both monkey cDNAs were
      individually expressed in a mammalian cell (CHO) line. Enzyme activities of both
      monkey SRs were localized to the membrane fractions of CHO cell extracts. Like
      the human and rat enzymes, the monkey type 1 and type 2 SRs were most active at
      neutral and low pH, respectively. The results of inhibition studies with over 30
      known SR inhibitors, including epristeride, 4MA, and finasteride, indicate that
      the monkey SR isoenzymes are functionally more similar to the human than the rat
      homologues. The results from initial velocity and inhibition studies as functions
      of pH with the human and monkey type 2 SRs also compare favorably. These results,
      together, suggest that the monkey SR isoenzymes are structurally and functionally
      comparable on a molecular level to their respective human counterparts,
      supporting the relevance and use of the Cynomolgus monkey as a pharmacological
      model for in vivo evaluation of SR inhibitors.

PMID- 7734400
TI  - In vivo regulation of the steroidogenic activity of rat luteal cells by insulin.
AB  - The aim of the present study was to determine the long-term effects of insulin
      treatment on luteal cell function. For this purpose, superovulated prepubertal
      rats were treated with insulin (group I) or vehicle (group C) for 9 days. Serum
      progesterone (P4) levels were increased in the insulin-treated group (55 +/- 10
      vs 134 +/- 31 ng/ml, P < 0.05). Isolated luteal cells were incubated 3 h, and P4
      and 20 alpha-hydroxy-progesterone (20 alpha-OH-P) were measured in the incubation
      media. A decrease in P4 levels and an increase in 20 alpha-OH-P values [P4
      (ng/ml): C = 26.6 +/- 0.3; I = 20 +/- 2; 20 alpha-OH-P (ng/ml): C = 62 +/- 2; I:
      120 +/- 7; P < 0.01] were observed in group I. In addition, progestagen (P4 + 20
      alpha-OH-P) levels were higher in group I (C = 88 +/- 2; I = 140 +/- 9 ng/ml; P <
      0.001). When cytochrome P450scc contents were measured by immunoblotting, a
      marked increase was observed in luteal cells obtained from group I. LH receptor
      numbers were decreased in luteal cells isolated from group I (C = 388,834 +/-
      14,146; I = 303,057 +/- 13,392 sites/cell; P < 0.001) with a concomitantly
      diminished LH responsiveness. It is concluded that in vivo treatment of
      superovulated rats with insulin increases luteal progestagen production by
      increasing the content of cytochrome P450scc.

PMID- 7734401
TI  - Co-expression of two distinct isoforms of 11 beta-hydroxysteroid dehydrogenase in
      the ovine placenta.
AB  - We have previously described two distinct isoforms of 11 beta-hydroxysteroid
      dehydrogenase (11 beta-HSD) with respect to enzymatic activity in the ovine liver
      and kidney. To determine which isoform(s) is expressed in the ovine placenta, we
      studied the characteristics of 11 beta-HSD activity in placental tissues
      collected at days 140-143 of pregnancy. 11 beta-HSD activity was determined by a
      radiometric conversion assay using cortisol and cortisone as physiological
      substrates. At 100 nM cortisol, the placental 11 beta-HSD utilized NAD as
      cofactor, but displayed preference for NADP at 10 microM cortisol. Kinetic
      characteristics were examined in the presence of alternate cofactors, in order to
      determine whether this difference in the cofactor requirement represents distinct
      enzymes. With NAD as cofactor, the placental 11 beta-dehydrogenase had a Km (110
      +/- 18 nM) compatible with the kidney enzyme, but displayed a Km (12 +/- 2
      microM) similar/identical to the liver 11 beta-HSD when NADP was used. By
      contrast, the placental 11-oxoreductase showed preference for NADPH regardless of
      cortisone concentration. Kinetic analysis, using NADPH as cofactor, revealed a
      single species of 11-oxoreductase activity with a Km of 4 +/- 0.9 microM and a
      Vmax of 3.1 +/- 0.5 pmol/mg/min. Finally, since the NAD-dependent 11 beta-HSD in
      the ovine placenta displayed similar/identical kinetic characteristics to the
      enzyme described previously in the ovine kidney where a truncated 11 beta-HSD
      transcript was identified, we have also determined whether this transcript is
      expressed in the placenta by Northern blotting. It was found that the truncated
      11 beta-HSD transcript was undetectable in the total RNA samples. These results
      demonstrate that both liver- and kidney-types of 11 beta-HSD activities are
      expressed in the ovine placenta, thus providing further evidence for the
      existence of a NAD-dependent 11 beta-HSD distinct from the well-characterized
      hepatic NADP-dependent enzyme. Furthermore, the lack of the truncated 11 beta-HSD
      transcript in the placenta suggests that the NAD-dependent enzyme identified in
      placenta and kidney is the product of a gene distinct from 11 beta-HSD.

PMID- 7734402
TI  - Expression of hsp90 beta messenger ribonucleic acid in patients with familial
      glucocorticoid resistance--correlation to receptor status.
AB  - We have previously shown an increased specific DNA-binding of liganded
      unactivated glucocorticoid receptor (GR) to the LTR-region of MMTV DNA in a
      patient with primary cortisol resistance and receptor thermolability indicating a
      defective interaction of GR with hsp90. In some patients, however, no apparent
      receptor abnormality was found in spite of a characteristic phenotype. mRNA
      expression levels of hsp90 beta were analysed in cultured fibroblasts from
      patients with known receptor defects, such as thermolability, decreased ligand
      binding affinity and low receptor expression levels, and from patients with a
      cortisol resistant phenotype but no detected receptor alteration. Fibroblasts
      from patients with GR defects expressed higher hsp90 beta mRNA levels as compared
      to patients with no receptor defects or to healthy controls. These data indicate
      that GR defects are associated with increased hsp90 beta mRNA levels.

PMID- 7734403
TI  - Expression of cytochrome P450 1A1, an estrogen hydroxylase, in ovarian granulosa
      cells is developmentally regulated.
AB  - In this paper we report the analysis of porcine ovarian granulosa cells for the
      expression of several known hepatic estrogen hydroxylase RNAs. Of the P450s
      examined, only CYP 1A1 RNA was detected. Accordingly, the regulation of this mRNA
      was studied. The RNA for CYP 1A1 was dramatically and completely induced within 2
      hours after exposure of immortalized granulosa cells to 3-methyl-cholanthrene
      (3MC) and expression could be inhibited with 10 microM phorbol myristate acetate.
      This message was also inducible by 3MC in cultured primary granulosa cells
      isolated from immature and developing follicles. Dexamethasone increased the
      relative expression of CYP 1A1 RNA in 3MC treated cells. In the absence of 3MC,
      the CYP 1A1 message was expressed in cultured granulosa cells from developing but
      not immature follicles, indicating developmental regulation of this enzyme.
      Further support for developmental regulation was provided by studies which
      detected the appearance of CYP 1A1 RNA during growth of ovarian follicles in
      vivo. This is the first report identifying a specific P450 estrogen hydroxylase
      RNA in ovarian granulosa cells.

PMID- 7734404
TI  - FK143, a novel nonsteroidal inhibitor of steroid 5 alpha-reductase: (1) In vitro
      effects on human and animal prostatic enzymes.
AB  - Steroid 5 alpha-reductase is an enzyme which converts testosterone into 5 alpha
      dihydrotestosterone (DHT) and is implicated in the pathogenesis of benign
      prostatic hyperplasia (BPH) in men. We studied in vitro effects of FK143, a
      nonsteroidal new compound, on 5 alpha-reductase in human and animal prostates.
      Prostates were obtained from Wistar rats, Beagle dogs, and Cynomolgus monkeys as
      well as prostatic tissue from BPH patients obtained by the prostatectomy. Nuclear
      membrane fraction of prostates showed pH dependent 5 alpha-reductase activities,
      and inhibitory effects of drugs were assayed at pH 6.5. FK143 inhibited human
      prostatic 5 alpha-reductase in a dose-dependent manner with an IC50 of 1.9 nM and
      also inhibited animal 5 alpha-reductases with similar IC50 values. FK143
      inhibited human and rat 5 alpha-reductases in a noncompetitive fashion while
      finasteride, a steroidal 5 alpha-reductase inhibitor, showed competitive
      inhibition. The affinities of FK143 for the human 5 alpha-reductase is constant
      at pH 5 and 6.5. No inhibitory effects were shown to other oxidoreductases. These
      results indicate that FK143 is a new type of potent and selective 5 alpha
      reductase inhibitor.

PMID- 7734405
TI  - FK143, a novel nonsteroidal inhibitor of steroid 5 alpha-reductase: (2) In vivo
      effects on rat and dog prostates.
AB  - FK143 is a nonsteroidal new inhibitor of steroid 5 alpha-reductase, an enzyme
      which converts testosterone into 5 alpha-dihydrotestosterone (DHT). We studied in
      vivo effects of FK143 on rat and dog prostates. FK143 was orally administered to
      mature male rats for 14 days. At doses above 1 mg/kg, FK143 significantly reduced
      the wet weights of the ventral prostate and seminal vesicle, but showed no
      effects on those of the epididymis, testis, and adrenal. Growth of ventral
      prostate and seminal vesicle was induced by the subcutaneous injection of
      testosterone propionate (TP) in the castrated young rats and was reduced by FK143
      administration at doses above 3.2 mg/kg, while growth induced by 5 alpha
      dihydrotestosterone propionate (DHTP) was not affected. FK143 had no binding
      affinity for the rat androgen receptor. FK143 showed neither estrogenic and
      antiestrogenic effects on the rat uterus nor androgenic effect on the rat
      prostate. Concentration of testosterone and DHT in the rat and dog prostates were
      measured by GC-MS, and administration of 10 mg/kg of FK143 significantly reduced
      the intraprostatic concentration of DHT. These results indicate that FK143
      reduced the prostate growth by inhibiting 5 alpha-reductase activities in the
      prostates.

PMID- 7734408
TI  - Reproducibility of semi-automated cell cycle analysis of flow cytometric DNA
      histograms of fresh breast cancer material.
AB  - DNA-variables such as DNA-ploidy, DNA-index and %S-phase cells have been proven
      to have prognostic value for breast cancer patients. These variables can be
      obtained by interpreting DNA-histograms by cell cycle analysis. Since there are a
      number of potential error sources, the aim of this study was to determine the
      intra- and inter-observer reproducibility of semi-automated cell cycle analysis
      with the emphasis on DNA ploidy and %S-phase assessments. The 149 DNA-histograms
      we used were randomly selected from the Multicentre Morphometric Mammary
      Carcinoma Project, a nationwide prospective study in The Netherlands on the
      reproducibility and prognostic power of quantitative assessments. These DNA
      histograms were obtained by flow cytometry of fresh frozen breast cancer
      material. Cell cycle analysis was performed according to a strict protocol with
      the semi-automated computer program 'MultiCycle', using the background correction
      option; 68 histograms were analyzed in duplicate by the same observer, and 81
      histograms were analyzed by two observers. Assessment of DNA-ploidy showed an
      intra-observer concordance of 99% (kappa-value 0.98) and an inter-observer
      concordance of 94% (kappa-value 0.91). The disagreement could be attributed to
      overlooking a DNA-tetraploid cell cycle in one case, some difficult histograms
      and varying opinions about small peaks between the observers in a few cases.
      Intra-observer %S-phase correlation coefficients varied between 0.72 for the %S
      phase of the second aneuploid cell cycle and 0.99 for the %S-phase of the diploid
      cell cycle. Inter-observer correlation coefficients varied between 0.81 for the
      %S-phase of the second cell cycle and 0.95 for the %S-phase of the diploid cell
      cycle and the average %S-phase cells. As for DNA-index, intra- and inter-observer
      correlation coefficients were 0.97 and 0.94, respectively. In conclusion, intra-
      and inter-observer reproducibility of semi-automated cell cycle analysis of flow
      cytometric DNA-histograms from fresh breast cancer material using the Multi-Cycle
      program, following a strict protocol, is in principle high. The results of this
      study may help us to decide which of the different %S-phases provided by cell
      cycle analysis software should be used in daily practice.

PMID- 7734407
TI  - Effect of aging on urinary excretion of 19-noraldosterone and 18,19
      dihydroxycorticosterone.
AB  - 19-Noraldosterone, recently shown to be produced in the human adrenal gland,
      possesses potent mineralocorticoid and hypertensinogenic activity. A possible
      precursor, 18,19-dihydroxycorticosterone, has been identified in human urine,
      with both steroids acutely regulated by the renin-angiotensin system. The
      secretion of aldosterone declines with advancing age. To elucidate the effect of
      aging on the urinary excretion of 19-noraldosterone and 18,19
      dihydroxycorticosterone, we measured their urinary concentrations in 51
      normotensive subjects aged 20-70 years. We observed significant negative
      correlations between age and the urinary excretion of 19-noraldosterone and 18,19
      dihydroxycorticosterone (r = -0.69, r = -0.65, P < 0.05, respectively). Urinary
      and plasma aldosterone and PRA similarly decreased with aging. These results
      suggest that 19-noraldosterone may be chronically regulated in part by the renin
      angiotensin system.

PMID- 7734406
TI  - Regulation of Sertoli cell aromatase activity by cell density and prolonged
      stimulation with FSH, EGF, insulin and IGF-I at different moments of pubertal
      development.
AB  - Sertoli cell aromatase activity is high in very young animals and declines
      throughout pubertal development. Little is known about the regulatory factors
      which might be involved in the pronounced decline suffered by this enzymatic
      activity. In this paper we show that estradiol production in Sertoli cells is
      dependent on cell density in the culture and that chronic stimulation with
      hormones can decrease estradiol acute response to FSH. In 8-day-old Sertoli cells
      cultured at low density (LD: 7.1 +/- 0.3 micrograms DNA), estradiol production
      was 151 +/- 11 pgE2/micrograms DNA, while in those cultured at high density (HD:
      30.3 +/- 0.6 micrograms DNA), production was 30 +/- 5 pgE2/micrograms DNA.
      Similar results were obtained in 20-day-old Sertoli cell cultures (LD: 57 +/- 4
      pgE2/micrograms DNA vs HD: 26.0 +/- 0.6 pgE2/micrograms DNA). On the other hand,
      treatment of Sertoli cell cultures (8- and 20-day-old) for 96 h, with FSH (100
      ng/ml), EGF (50 ng/ml), insulin (10 micrograms/ml) and IGF-I (50 ng/ml) at
      different densities resulted mostly in inhibition of aromatase activity. The
      effect caused by FSH was apparently not related to desensitization as
      aromatization with dbcAMP could not overcome the decreased ability of these cells
      to produce estradiol. The effect caused by EGF was observed in 8-day-old Sertoli
      cells cultured under high density conditions. Marked inhibition was observed with
      insulin and IGF-I in 8-day-old Sertoli cell cultures. Considering previous
      reports indicating a decrease in Sertoli cell aromatase activity with age, our
      results suggest a potential role for FSH, EGF, insulin and IGF-I on the Sertoli
      cell differentiation process which occurs throughout pubertal development.

PMID- 7734409
TI  - In vivo bromodeoxyuridine (BrdU)-labelling index of rat thymus: influence of
      different BrdU doses and exposure times as analyzed both in tissue sections and
      in single cell suspensions.
AB  - Tissue sections and single cell suspensions of rat thymus were analyzed by flow
      and image cytometry to study the effects of different doses of bromodeoxyuridine
      (BrdU) (10, 50 and 100 mg/kg and different labelling periods (15, 30 and 60 min)
      on the BrdU-labelling index. The proportions of BrdU-labelled cells, as analyzed
      by flow cytometry, were similar in the different groups of our study. However,
      the quality of the results was not exactly the same, since when the BrdU dose
      decreased, the separation between BrdU-positive S-phase cells and both the G0/G1
      and the G2/M BrdU-negative cells on a DNA/BrdU histogram became less clear. On
      the other hand, the proportion of BrdU-labelled cells in tissue sections was
      greater in the groups of animals that received doses of 100 mg/kg and were killed
      15, 30 or 60 min later than in the sections obtained from the remaining groups.
      Our results show that both dose and exposure time to BrdU may influence the final
      results when cell proliferation is assessed, the variations obtained clearly
      depending on the technique used for the immunological detection of BrdU-positive
      S-phase cells.

PMID- 7734410
TI  - Differences in quantitative nuclear features between ductal carcinoma in situ
      (DCIS) with and without accompanying invasive carcinoma in the surrounding
      breast.
AB  - The aim of this study was to demonstrate differences in nuclear morphology
      between ductal carcinoma in situ (DCIS) without an invasive component and DCIS
      associated with invasive carcinoma in adjacent breast tissue. DCIS specimens of
      60 non-comedo and 21 comedo cases were obtained from two groups of patients with
      or without invasive carcinoma of the breast. The analysis of DCIS nuclei was
      performed on formalin fixed deparaffinized thin sections stained with a
      stoichiometric stain following the Feulgen procedure. Nuclear features, related
      to nuclear size, shape and DNA distribution, were quantitatively characterized by
      high resolution image cytometry. Features associated with the presence of
      invasive carcinoma in the surrounding breast tissue were identified in DCIS
      nuclei (independent of nuclear grade). Features selected by the stepwise
      procedure of the discriminant function analysis were typically texture features
      describing the DNA distribution in the nucleus. A classification function based
      on the selected nuclear features predicted accurately the presence of invasive
      carcinoma in all comedo DCIS and in 80% of non-comedo DCIS cases. Our results
      indicate that quantitative nuclear features of DCIS nuclei are predictive of the
      accompanying invasion and may be helpful as a new tool in evaluation of DCIS
      patients.

PMID- 7734411
TI  - Simultaneous in situ hybridization with biotin-labeled centromeric and library
      DNA probes: a useful method for identifying translocations.
AB  - A method of in situ hybridization is described for rapid characterization of
      cytogenetical translocations. In the same experimental procedure, biotinylated
      centromeric and 'painting' DNA probes were used in combination. Signals of the
      double-target hybridization were visualized by only one fluorescein. This
      technique also permits a simultaneous detection of multiple unrelated aberrations
      involving several chromosomes.

PMID- 7734412
TI  - Higher reproducibility of morphometric analysis over the counting method for
      interphase AgNOR quantification.
AB  - In a series of 40 breast carcinomas, the reproducibility of two different methods
      for interphase AgNOR quantification was evaluated. Two operators independently
      defined on each slide the interphase AgNOR quantity both by measuring the area of
      the silver-stained structures using image cytometry and counting the AgNOR number
      directly at the microscope. The correlation between the values obtained by the
      two observers was statistically significant, but the correlation coefficient
      between AgNOR areas (r = 0.79; P < 0.001) was greater than that between AgNOR
      numbers (r = 0.38; P = 0.014). On the other hand, when interphase AgNOR area and
      number values obtained by each observer were compared, no significant correlation
      was found. This study has demonstrated that the two different methods for
      interphase AgNOR quantification are not comparable, and that morphometric
      analysis is more objective and reproducible than the counting method.

PMID- 7734413
TI  - Consensus report of the ESACP task force on standardization of diagnostic DNA
      image cytometry. European Society for Analytical Cellular Pathology.

PMID- 7734414
TI  - CD38 unresponsiveness of xid B cells implicates Bruton's tyrosine kinase (btk) as
      a regular of CD38 induced signal transduction.
AB  - CD38 is a 42 kDa membrane-associated ectoenzyme expressed by a large proportion
      of human and mouse lymphocytes. Agonistic antibodies to CD38 induce a strong
      proliferative response in lymphocytes additionally co-stimulated with other
      growth co-factors such as IL-4, IL-2 plus accessory cells or sub-mitogenic doses
      of endotoxin. We show here that B lymphocytes from unstimulated X-linked
      immunodeficient (xid) mice are unresponsive to CD38 stimulation, both in terms of
      proliferative response and surface antigen modulation. This CD38 unresponsiveness
      is evident in the presence of excess quantities of, and normal responses to, the
      accessory growth co-stimulants required for this response. CD38 molecules
      expressed on xid B cells are normal in terms of expression levels, size and
      enzymatic activity, suggesting that CD38 unresponsiveness reflects a down-stream
      signaling defect. In light of the recent proposal that the xid gene encodes a
      tyrosine kinase called Bruton's tyrosine kinase (btk), these data suggest that
      btk is either an integral component or an indirect regulator of the CD38-induced
      signal transduction pathway.

PMID- 7734415
TI  - Competition of HLA-DR and a beta 2 domain peptide for HIV envelope glycoprotein
      gp120 binding to CD4.
AB  - HLA class II molecules and the HIV envelope glycoprotein gp120 are ligands of
      CD4. Reciprocal interaction sites have been well characterized for gp120 and CD4,
      but require further definition for HLA class II and CD4. A major CD4 binding site
      encompassing amino acids 134-148 in the beta 2 domain of HLA-DR has been
      previously identified. Recently, we have shown, by extensive characterization of
      mutated CD4 molecules expressed in COS cells, that HLA class II antigens interact
      mainly through the HIV gp120 binding site and possibly through a second minor
      interaction site mapping on the same face of the molecule. Based on the direct
      binding in vitro of iodinated affinity-purified HLA-DR1 molecules to polystyrene
      immobilized human IgG3-CD4, we now report on reciprocal binding inhibition of
      gp120, HLA-DR1 and the DR beta 2 synthetic peptide to CD4. The results strongly
      suggest that gp120 and the beta 2 region (amino acids 134-148) of HLA-DR1 bind
      mainly to the same part of CD4 domain 1 and that the CD4 binding site of HLA-DR
      requires the existence of a class II homodimer. In that case, alpha 2 chain
      residues might interact with CD4 residues different from those involved in the
      binding of gp120 but located close to them in the first domain.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7734416
TI  - T cell antigen receptor engagement abrogates CD4-mediated T cell deletion in
      vivo.
AB  - We have previously shown that the engagement of CD4 by specific antibody in the
      mouse initiates a T cell apoptosis response with the following features: spleen
      and lymph node CD4+ T cells migrate into the bloodstream within minutes of anti
      CD4 administration where they exhibit the phenotype of null cells. If they are
      capable of expressing functional Fas protein on their surface they degrade their
      DNA and disintegrate rapidly. We show here that the engagement of the T cell
      antigen receptor blocks the CD4-mediated deletion process in mouse. Anti-CD4
      reactive T cells avoid the exodus into the bloodstream when their TCR is engaged
      by anti-CD3 or by a superantigen, do not modulate surface receptors and are not
      deleted. In contrast to the apoptosis-inducing CD4-specific antibody which causes
      migration of lymphocytes from lymphoid organs into the blood stream, the T cell
      activating CD3-specific antibody causes lymphoid cell redistribution in the
      opposite direction, from the bloodstream to lymphoid organs. The TCR-mediated
      protection of T cells against CD4-mediated deletion lasts for several hours but
      ceases before the T cells become blasts.

PMID- 7734417
TI  - CD38 expression on mouse T cells: CD38 defines functionally distinct subsets of
      alpha beta TCR+CD4-CD8- thymocytes.
AB  - We have examined CD38 expression on mouse lymphocytes using the rat mAb NIM-R5
      and demonstrate that CD38 expression is restricted to approximately 8% of
      thymocytes. Although CD38 is absent from the majority of CD4+CD8- and CD4-CD8+ T
      cells, we detected a strong correlation between CD38 expression and alpha
      beta+CD4-CD8- T cells in the thymus, with nearly 80% of alpha beta TCR+CD4-CD8-
      thymocytes being CD38+. Using heat stable antigen (HSA) and CD38, we divided
      alpha beta+CD4-CD8- thymocytes into four subsets: HSA+CD38-, HSA-CD38hi, HSA
      CD38low and HSA-CD38-. Two established characteristics of alpha beta TCR+CD4-CD8-
      cells, bias towards V beta 8.2 TCR expression and high levels of IL-4 production,
      were used to establish a possible relationship between the above thymocyte
      subsets. Our present data show that the HSA+CD38- subset is not biased towards V
      beta 8.2 TCR expression whereas the HSA-CD38- subset does show this bias
      (approximately 47%). Neither of these subsets make IL-4 upon CD3 mediated
      stimulation. In contrast, the CD38+ subsets are heavily biased toward V beta 8.2
      expression and produce large amounts of IL-4 upon stimulation, particularly the
      CD38low cells. Taken together, these data suggest that these four subsets
      represent various stages of a possible differentiation pathway for alpha beta
      TCR+CD4-CD8- cells, with the HSA+CD38- subset being the most immature while the
      HSA-CD38low subset is the most functionally mature. These characteristics support
      the view that alpha beta TCR+CD4-CD8- T cells represent an independent lineage
      with a distinct, but as yet obscure, role in immunity.

PMID- 7734418
TI  - Peptide motifs of HLA-B51, -B52 and -B78 molecules, and implications for Behcet's
      disease.
AB  - Here we report peptide motifs of five HLA-B molecules, B*5101, B*5102, B*5103
      B*5201 and B*7801. Motifs were obtained by pool sequencing of natural ligands
      eluted from the respective molecules expressed in C1R cells upon transfection. A
      number of individual ligands that could be sequenced confirmed the motifs. All
      five HLA-B molecules belong to the HLA-B5, B35-cross-reactive group and are
      closely related as indicated by similar sequences. B51 and B52 are associated
      with Bw4, whereas B78 is associated with Bw6. One of the HLA-B molecules
      investigated here, HLA-B*5101, is associated with Behcet's disease, a
      multisystemic inflammatory disease affecting various organs. This disease is
      especially frequent among the Japanese population. The subtle differences between
      the peptide motifs of B*5101 as compared with the motifs of the four other
      closely related but not disease-associated molecules could shed light on the
      nature of the HLA-association of Behcet's disease.

PMID- 7734419
TI  - Inhibition of HIV-1 by modification of a host membrane protease.
AB  - While it is clear that CD4 is the receptor for the gp120 envelope protein of HIV
      1, substantial evidence suggests that other host cell proteins are required for
      successful membrane fusion. Studies were initiated to examine the potential for a
      protein receptor which has an elastase-like character to participate in fusion of
      HIV-1 with permissive host cells. A synthetic elastase inhibitor was shown to
      significantly reduce HIV-1 infectivity when present during, but not after, the
      initial contact between virus and cells. A human T cell elastase-like membrane
      component was purified and shown to be lipid-associated. By competitive
      inhibition, the purified protein was shown to bind gp160 within the HIV-1 fusion
      domain. The binding parameters of whole T cell membrane extract, with a
      hydrophobic pentapeptide representative of the fusion domain, suggested an
      elastase-like protein is the single, secondary T cell receptor for HIV-1 (K = 1 x
      10(3) M-1). The pentapeptide interacted with porcine and human (epithelial and
      polymorphonuclear leukocyte), but not murine, elastase isoforms, suggesting its
      participation in the permissiveness of host cells to infection.

PMID- 7734420
TI  - Expression and function of fibronectin binding integrins on rat mast cells.
AB  - Adhesion molecules of the integrin family are implicated not only in leukocyte
      migration but also in leukocyte activation. Here we characterize the expression
      and function of fibronectin receptor integrins on rat mast cells. A rat
      basophilic leukemia cell line (RBL-2H3) and phorbol ester-stimulated rat
      peritoneal mast cells adhered to fibronectin (FN), vitronectin and fibrinogen.
      These mast cells expressed fibronectin receptor integrins, including very late
      antigen (VLA)-4, VLA-5 and vitronectin receptor (VNR), as estimated by
      immunofluorescent staining and inhibition of FN adherence by newly established
      mAbs reactive with the rat alpha 4 (MR alpha 4-1), alpha 5 (HM alpha 5-1) or beta
      3 (HM beta 3-1) chains of the integrin molecules. The beta-hexosaminidase
      release, a marker for mast cell degranulation, triggered by high affinity IgE
      receptor (Fc epsilon RI)-mediated stimulation, was enhanced by adhesion of RBL
      2H3 cells to either immobilized FN, MR alpha 4-1, HM alpha 5-1 or HM beta 3-1.
      This FN enhancement of beta-hexosaminidase release was inhibited by soluble MR
      alpha 4-1, HM alpha 5-1 and HM beta 3-1 as well as by GRGDSP and
      DELPQLVTLPHPNHLGPEILDVPST peptides which abrogate VLA-5/VNR and VLA-4 binding to
      FN respectively. In vivo, passive cutaneous anaphylaxis induced by IgE anti-DNP
      and DNP-BSA was inhibited by concurrent s.c. injection of MR alpha 4-1, HM alpha
      5-1 and HM beta 3-1. These results demonstrate that FN receptor integrins
      expressed on rat mast cells play an important role in regulating mast cell
      activation both in vitro and in vivo.

PMID- 7734421
TI  - IL-2 inhibits IL-4-dependent IgE and IgG1 production in vitro and in vivo.
AB  - Nippostrongylus brasiliensis (Nb) infection of mice induces IL-4 producing CD4+ T
      cells which stimulate polyclonal IgE and IgG1 production, providing a model
      system to study IL-4 action on B cells in vivo. B cell Ia expression and the
      proportion of IL-2R beta positive B cells were increased in Nb-inoculated mice,
      and B cells from these mice responded to IL-2 by prompt and marked cell growth.
      Injection of anti-IL-4 1 day after Nb inoculation substantially inhibited these
      responses, indicating that they were largely IL-4 dependent. Thus IL-4 acted as a
      polyclonal B cell activator in vivo and caused B cells to develop into IL-2
      responsive cells. Furthermore, injection of IL-2 inhibited IgG1 and IgE
      production by Nb-inoculated mice. To understand the mechanism of this IL-2
      mediated inhibition, we used an in vitro IgG1 and IgE induction system. B cells
      from Nb-inoculated mice displayed an increase in the capacity of IL-2 to inhibit
      lipopolysaccharide (LPS) plus IL-4-driven IgE and IgG1 production, indicating
      that B cells expressing IL-2R beta are highly sensitive to IL-2. This inhibition
      was principally dependent upon the direct action of IL-2 on B cells. However,
      partial abolition of IL-2 inhibitory action by anti-IFN-gamma treatment suggested
      that endogenous IFN-gamma released from IL-2-stimulated cells was also involved
      in this IL-2-mediated IgE and IgG1 inhibition. Northern blot analysis
      demonstrated that IL-2 inhibited IL-4 induction of germline and productive C
      epsilon transcripts in LPS-stimulated B cells. Digestion-circularization
      polymerase chain reaction analysis revealed IL-2 inhibited IL-4 induction of s mu
      s gamma 1 rearrangement in LPS-stimulated B cells.

PMID- 7734422
TI  - Mutations in residue 61 of H-Ras p21 protein influence MHC class II presentation.
AB  - We have investigated the influence of mutations in the Ras 61 codon on the
      immunogenicity of synthetic peptides and H-Ras p21 proteins. H-2k mice produced
      Th responses when immunized with mutated peptides in which the Gln at position 61
      in the wild type sequence was replaced by Leu (L) or His (H). T cell hybridomas
      specific for the 61L and 61H peptides were then produced. The responses of both
      were I-Ak restricted. Competition experiments indicated that the wild type
      peptide did not bind to the I-Ak molecule whereas the two mutations generated a
      site on the peptides that was agretopic for the I-Ak molecule. Nevertheless the
      recognition of the corresponding Ras proteins was highly dependent upon the
      nature of the substitution. The H-Ras p21 protein with the 61L mutation (61L) was
      processed by syngeneic splenocytes and the epitope dependent on 61L was
      recognized as efficiently as the corresponding peptide by the T cell hybridoma
      specific for 61L. In contrast, the processing of H-Ras p21 with the 61H mutation
      (61H) was probably inefficient in producing the epitope recognized by the
      hybridoma specific for 61H. Furthermore, immunization studies with the two
      mutated H-Ras p21 proteins suggest that only the 61L substitution can be
      exploited for immunotherapy. Thus this work demonstrates that any peptide
      immunotherapy must be undertaken with the reservation that not all oncogenic
      mutations at codon 61 will be amenable to immune therapy.

PMID- 7734423
TI  - Selection of peripheral and intestinal T lymphocytes lacking CD3 zeta.
AB  - The CD3 zeta chain of the TCR plays a pivotal role in the activation of T cell
      responses toward foreign antigen and in the selection of the T cell repertoire. T
      lymphocytes from mice deficient in CD3 zeta (CD3 zeta/eta-/- mice) express very
      few cell surface TCR-CD3 complexes, and these animals have poorly developed
      thymuses which lack single-positive CD8 and CD4 thymocytes. Nevertheless, a
      substantial number of single-positive CD4+ and CD8+ T lymphocytes are found in
      peripheral lymphoid organs of CD3 zeta/eta-/- animals. Using double-mutant mice,
      generated by breeding CD3 zeta/eta-/- mice with others deficient in the
      expression of either class I or class II MHC molecules, we demonstrate here that
      positive selection of peripheral CD4+ and CD8+ T lymphocytes can occur in the
      absence of CD3 zeta/eta molecules. Analysis of the intestinal intra-epithelial
      lymphocytes from CD3 zeta/eta-/- mice revealed a novel T cell population
      expressing high levels of an alternative TCR alpha beta, due to the replacement
      of CD3 zeta by Fc epsilon RI gamma. Developmentally, these cells also depend on
      class I MHC expression. In contrast, TCR gamma delta/Fc epsilon RI gamma+ T cells
      develop independently of MHC class I or class II molecules. These experiments
      demonstrate that the unique subset of intestinal TCR alpha beta/Fc epsilon RI
      gamma+ lymphocytes is developmentally dependent on MHC expression. The restricted
      expression of TCR alpha beta/Fc epsilon RI gamma+ cells in the intestinal mucosa
      (rather than the thymus or lymph nodes) supports the hypothesis that selection of
      these T cells occurs extrathymically.

PMID- 7734424
TI  - Co-stimulation lowers the threshold for activation of naive T cells by bacterial
      superantigens.
AB  - Staphylococcus enterotoxins bind class II MHC molecules on antigen presenting
      cells (APC) and stimulate T cells expressing appropriate V beta gene products.
      Although the role of non-TCR associated co-stimulatory receptors during antigen
      specific T cell stimulation has been clearly established, the involvement of co
      stimulatory activity in T cell activation by superantigens has been the matter of
      controversy. In this report, we examine the role of co-stimulation provided by
      selected APC populations in the response to bacterial exotoxins (staphylococcal
      enterotoxin A, staphylococcal enterotoxin B and toxic shock syndrome type 1). We
      demonstrate that the APC population able to activate naive T cells to IL-2
      production is heterogeneous, comprising both adherent (presumably dendritic) and
      non-adherent (mostly B lymphocytes) cells. By stimulating naive T cells in the
      presence of graded doses of superantigens, we have observed that half-maximal IL
      2 production was achieved at lower doses of superantigens in the presence of
      dendritic cells. Similarly, addition of antibodies to CD28 or B7.1-transfected
      cell lines increased the sensitivity of naive T cells to lower doses of
      superantigens. These observations indicate therefore that superantigens can be
      presented to naive T cells by APC displaying distinct levels of co-stimulatory
      activity, although with different efficacy. Thus, naive T cells are sensitive to
      CD28-mediated co-stimulation during superantigen-mediated responses but IL-2
      production can be induced by high doses of superantigens in the presence of APC
      expressing weak co-stimulatory activity. These observations are compatible with
      the hypothesis that CD28-mediated signals participate in T cell activation by
      lowering T cell sensitivity to TCR ligands.

PMID- 7734425
TI  - A monovalent C mu 4-specific ligand enhances the activation of human B cells by
      membrane IgM cross-linking ligands.
AB  - The ligand-receptor binding requirements for achieving full B cell activation
      through the membrane immunoglobulin (mIg) signaling pathway are relatively
      demanding, and mIg-antigen engagements which fall below these critical thresholds
      cause, at most, only the partial activation of B cells. In an effort to resolve
      new means of enhancing the efficacy of mIgM-mediated signal transduction, as well
      as to further understand the process by which mIgM-mediated signals are
      initiated, we have explored the mechanism for a previously reported synergy
      between certain mixtures of murine anti-IgM mAbs in eliciting human B cell DNA
      synthesis. We here report that striking synergy occurs when any of several
      relatively high affinity mAbs specific for diverse domains of mIgM are combined
      in culture with the relatively low affinity C mu 4-specific ligand, mAb IG6.
      Although B cell activation was dependent upon the bivalency, and hence mIgM cross
      linking potential, of the high affinity ligand, low affinity mAb IG6 could
      enhance the activation process when present as a monovalent Fab' fragment. This
      did not appear due to F(ab')2 contamination or Fab' aggregation, since IG6 Fab'
      preparations were notably compromised in several other functions requiring ligand
      bivalency. Pulsing studies revealed that the C mu 4-specific ligand exhibits its
      functional effects only when stimulatory mIgM receptor cross-links are being
      formed by bivalent ligands, and that IG6 Fab' enhancement is most notable during
      the later interval of the prolonged mIgM signaling process that leads to S phase
      entry. A unique region of the membrane-proximal IgM domain may be important for
      Fab'-mediated enhancement, since Fab' fragments that bind with higher affinities
      to distinct sites on C mu 4 were not as effective at mediating this phenomenon.
      Several possibilities for the adjuvant effects of this C mu 4-specific Fab' on B
      cell responses triggered by mIgM crosslinking ligands are discussed, including
      the possibility that IG6 Fab' influences the potential for mIgM dimer formation
      or interactions of mIgM with other signal-transducing molecules.

PMID- 7734426
TI  - Long life span of tolerant T cells and the role of antigen in maintenance of
      peripheral tolerance.
AB  - To follow the fate of tolerant T cells in vivo we used a transgenic mouse model
      in which peripheral T cell tolerance was based on a non-deletional mechanism.
      These mice expressed two transgenes: the MHC class I molecule Kb under the
      keratin IV promoter on keratinocytes (2.4 KerIV-Kb) and an anti-Kb TCR identified
      by the anti-clonotypic antibody Desire-1 (DES-TCR). Although these mice were
      tolerant to Kb skin grafts, CD8+DES+ T cells were present in their lymphoid
      organs in the same numbers as in Kb-reactive DES-TCR single-transgenic mice. The
      unresponsiveness towards Kb grafts suggested previous contact of the CD8+DES+ T
      cells with the Kb molecule on keratinocytes, but the evidence was indirect. The
      present study demonstrates enhanced levels of activation markers like CD44 and
      CD2 on the tolerant T cells, indicating contact with the Kb molecule. Continuous
      presence of antigen was required for maintenance of the tolerant state as shown
      by transfer of tolerant T cells into Kb-negative nu/nu BALB/c mice. Three days
      after cell transfer most recipients were still tolerant and accepted Kb-positive
      skin grafts, but 2 weeks after transfer the transferred cells had recovered their
      responsiveness and rejected Kb grafts. In order to see if contact with the
      tolerogen would eventually drive the tolerant cells into cell death, the life
      span of tolerant CD8+DES+ cells was measured in thymectomized DES-TCR x 2.4 KerIV
      Kb double-transgenic mice. The tolerant cells were found to have a life span of
      at least 8 weeks, which was comparable with the life span of non-tolerant
      CD8+DES+ cells from DES-TCR single-transgenic mice. Thus, tolerant T cell
      populations can be long-lived and need continuous contact with the tolerogen to
      remain tolerant.

PMID- 7734427
TI  - Identification of polymorphisms in the constant region of IgG3: the missing mouse
      allotype.
AB  - We have identified DNA sequence polymorphisms in the C gamma 3 genes of BALB/c
      and C57BL/6 mice. One of these results in a Ser-->Gly amino acid difference in
      CH1 at position 129 according to the Wu and Kabat numbering system. There are
      three additional silent substitutions in the coding region and two polymorphic
      nucleotides in the 3' untranslated region. According to standard nomenclature in
      which alleles are numbered according to the order of their identification, these
      C gamma 3 alleles are designated Igh-8a and Igh-8b respectively. We also describe
      two polymerase chain reaction-based assays that identify the allelic differences.

PMID- 7734428
TI  - Inhibitory effects of combined administration of 5-FU and Krestin on liver cancer
      KDH-8 in WKA/H rats.
AB  - The effectiveness of the combined administration of 5-fluorouracil (5-FU) and
      Krestin (PSK) on experimentally induced liver cancer has not been established.
      This study was undertaken to elucidate the effect of the combined administration
      of these drugs on tumor growth and metastasis. Male inbred WKA/H strain rats were
      used. The drugs used were 5-FU and PSK, each dissolved in water and fed orally.
      The drugs were administered separately or concurrently in standardized cycles to
      the tumor-bearing animals. KDH-8 ascitic liver cancer cells were subcutaneously
      transplanted into WKA rats. The tumor growth inhibition rates of 5-FU and PSK
      were then determined. Eighteen days after subcutaneous transplantation, tumor
      growth in the combined administration group was significantly inhibited, compared
      to the control group and the single treatment groups (p < .05). In addition, a
      liver metastatic model was prepared by transplanting KDH-8 cells into the spleen.
      Then the metastatic inhibitory effects of 5-FU and PSK were analyzed. At 14 days,
      the mean number of liver metastatic nodules was approximately 63 in the control
      group. However, the combined-medicated group showed a much lower number of
      nodules (40), indicating that metastasis was significantly inhibited (p < .05).

PMID- 7734429
TI  - Pumpless respiratory assistance using a membrane oxygenator as an artificial
      placenta: a preliminary study in newborn and preterm lambs.
AB  - Newborns suffering from severe respiratory difficulties and not responding to
      conventional methods have been successfully treated by extracorporeal circulation
      with a membrane oxygenator (ECMO). However, the technique needs a highly
      specialized staff, excellent laboratory support, and continuous surveillance of
      the procedure to prevent complications. In a series of experiments on newborn and
      preterm lambs, we have investigated a relatively simpler technique of respiratory
      support that involves a pumpless arteriovenous bypass by cannulating both
      umbilical arteries and the umbilical vein. A highly efficient microporous
      membrane oxygenator (MO) with very low resistance was selected. This type of
      perfusion that mimics the placental circulation, besides providing an additional
      amount of oxygen to the blood, has proven to be very effective for CO2
      extraction. Before its application in humans, however, improvements in the
      catheters to be inserted in the umbilical vessels, some modifications in the
      design of the MO, and improvements in the blood compatibility of all foreign
      surfaces in contact with blood are needed.

PMID- 7734430
TI  - Inflammatory intermediates produced by tissues encasing silicone breast
      prostheses.
AB  - Silicone prostheses, when implanted within the soft tissues of the breast, evoke
      an inflammatory reaction. In response to silicone exposure, inflammatory mediator
      production by individual cells has been observed in various experimental studies.
      In this study, inflammatory mediator production by periprosthetic tissues (whole
      organ) was measured. The mediator levels were correlated with both the tissue
      histopathology of the periprosthetic capsules and the clinical symptoms noted by
      each patient. Tissue surrounding breast implants removed at surgery from ten
      women (average age and implant duration 40 and 7 years respectively) was cultured
      in vitro for 24 hours. Control tissues consisting of (a) augmentation mammaplasty
      skin scars from eight additional patients and (b) knee synovium from seven
      orthopedic surgery patients with arthritis undergoing primary joint arthroplasty
      were similarly cultured. The mediators [interleukin-2 (IL-2), tumor necrosis
      factor-alpha (TNF-alpha), interleukin-6 (IL-6), and prostaglandin E2 (PGE2)]
      liberated into the culture media were measured by an enzyme linked immunosorbent
      assay. When compared to controls, the mediator levels of IL-6 and TNF-alpha were
      substantially greater, although IL-2 and PGE2 were lower. Levels varied greatly
      from patient to patient: in pg/ml per 10 g tissue, IL-2 ranged from 10 to over
      1,000; TNF-alpha from 100 to 1,000; IL-6 from 100 to 1,000,000; and PGE2 from 100
      to 10,000. The correlation between TNF-alpha and PGE2 levels was .5 between IL-6
      and PGE2 was .6, and between IL-6 and TNF-alpha was .77. The correlation between
      TNF-alpha and IL-6 was statistically significant at a p-value less than .01.
      Elevated levels of TNF-alpha production were associated with an increased number
      of macrophages and overall tissue cellularity (p < .05). No significant
      relationship was observed between mediator production and clinical symptoms. We
      conclude that overall cellularity, specifically macrophages, in the
      periprosthetic capsule may lead to TNF-alpha production but that cytokine
      production by periprosthetic tissues alone is not a predictor of clinical
      symptomatology in patients with silicone breast prostheses.

PMID- 7734431
TI  - Prolonged hypercholesterolemia induces reversible alterations in venous vasomotor
      function.
AB  - Hypercholesterolemia is associated with altered arterial endothelial and smooth
      muscle cell function. This study examines the influence of hypercholesterolemia
      on external jugular venous endothelial and smooth muscle cell vasoreactivity.
      Eighteen New Zealand White rabbits received a 1% cholesterol diet: in nine
      animals, this diet was continued until harvest at 8 weeks (hypercholesterolemic
      group), but in the other nine animals, the diet was changed to standard rabbit
      chow after 4 weeks and continued for a further 4 weeks (cholesterol reduction
      group). The change in the diet resulted in a 70% decrease in serum cholesterol
      concentration. Eight animals received standard rabbit chow for 8 weeks.
      Hypercholesterolemia induced hypersensitivity and increased maximal contractions
      to norepinephrine and endothelin-1. In addition, the maximal response to
      bradykinin increased, and a contraction to serotonin was induced in the veins
      from the hypercholesterolemic animals. Cholesterol reduction induced bradykinin
      hypersensitivity but had no effect on endothelin-1 sensitivity. Norepinephrine
      hypersensitivity returned to normal and the serotonin response disappeared. A
      decrease in the maximal contractile responses to these agonists was also
      observed. Hypercholesterolemia interfered with dose-dependent, EDRF (endothelium
      derived relaxing factor)-mediated relaxation induced by acetylcholine but,
      following the reduction of serum cholesterol, normal acetylcholine-induced,
      endothelium-dependent relaxation returned. Non-endothelium-dependent relaxation
      to sodium nitroprusside of precontracted veins was unaffected by the presence of
      high cholesterol concentrations. There were no morphological changes apparent in
      the veins of either the hypercholesterolemic or the cholesterol reduction groups.
      In conclusion, this study suggests that hypercholesterolemia induces reversible
      functional abnormalities in venous tissue and this ability of the jugular veins
      to recover may be, in part, linked to the lack of morphological changes.

PMID- 7734432
TI  - Protective effect of combined allopurinol and verapamil given at reperfusion in
      severe renal ischemia.
AB  - This study investigates the role of verapamil, a calcium channel blocker,
      combined with allopurinol, a xanthine-oxidase inhibitor, when given at
      reperfusion after severe renal ischemia injury in the rat. Male Sprague-Dawley
      rats were subjected to 60 minutes of warm ischemia by cross clamping the whole
      left renal pedicle (artery and vein). At the end of ischemia, the clamps were
      removed and a contralateral nephrectomy was performed. The animals (n = 40 per
      group) were divided into five groups; Group 1, ischemic control (IC) receiving
      lactated Ringer's; Group 2, allopurinol (A) 100 mg/kg; Group 3, verapamil (V)
      1.25 mg/kg; Group 4, receiving a combination of A + V at the same concentrations;
      and Group 5, sham group. Each drug was given intravenously at the end of the
      ischemic period at reperfusion. Survival was evaluated at 7 days. Renal damage
      was assessed by kidney function tests (serum creatinine and blood urea nitrogen,
      or BUN), light histology. Lipid peroxidation was measured in renal tissue using
      the TBA (thiobarbituric acid) assay. The best survival rate was seen in the
      combination group of A + V (70% at 7 days; p < .01 vs. control). Single drugs
      were not as effective as the combination when compared to the IC. Serum
      creatinine at 24 and 48 hours showed a significant difference between the IC and
      treatment groups. At 72 hours there were no differences among the treated groups.
      Histological damage was more pronounced in the IC (Grade 4.0) than in the
      allopurinol (3.4 +/- 0.8), verapamil (3.0), or A + V (2.2 +/- 0.04).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7734433
TI  - Effects of a water-soluble ethylhydroxyethyl cellulose on gut physiology,
      bacteriology, and bacterial translocation in acute liver failure.
AB  - Bacterial infection and bacteremia are common complications in patients with
      acute liver failure. Bacterial translocation from the gut has been suggested to
      be a major cause of bacterial infections in experimental acute liver failure. In
      the present study, a water-soluble ethylhydroxyethyl cellulose (EHEC) was
      administered orally 1 and 24 hours prior to 90% hepatectomy in the rat in order
      to prevent bacterial translocation in experimental acute liver failure induced by
      subtotal liver resection in the rat. Ninety percent hepatectomy alone resulted in
      80 to 100% translocation to mesenteric lymph nodes or blood 2 and 4 hours after
      operation. There was no translocation in rats undergoing sham operation or 90%
      hepatectomy with EHEC administration prior to operation (p < .01). Bacterial
      overgrowth, increased bacterial adherence onto the intestinal surface, and
      diminished intestinal and mucosal mass were also observed in animals with
      subtotal liver resection, but not in those administered EHEC. A delayed 2-hour
      intestinal transit time occurred in both groups receiving subtotal liver
      resection, with or without oral EHEC. EHEC inhibited bacterial growth and DNA
      synthesis and altered bacterial surface properties after 1-hour incubation with
      bacteria in vitro, an interaction that was not further influenced by time. These
      results imply that EHEC may alter enterobacterial capacities of metabolism,
      proliferation, and invasion by effects on the bacterial surface. Furthermore,
      EHEC seems to possess a trophic action on the intestine, though without enhancing
      the intestinal motility.

PMID- 7734434
TI  - Pattern of AMP degradation in ischemic rabbit lung tissue.
AB  - Because adenine nucleotide catabolites may be important during postischemic lung
      reperfusion, we examined the pathway of adenosine monophosphate (AMP) degradation
      in ischemic lung tissue. Once the pattern of degradation is known,
      pharmacological interventions can be considered, offering new methods of reducing
      lung reperfusion injury. For this purpose we used the isolated rabbit lung.
      Rabbit lungs were flushed in situ with a modified Krebs Henseleit solution (60
      ml/kg). The lungs were removed and stored deflated, immersed in saline solution
      at 37 degrees C. At regular times, biopsies were taken, and adenine nucleotides,
      nucleosides, and bases were measured in these biopsies using high performance
      liquid chromatography (HPLC). During lung ischemia, a very significant increase
      of inosine monophosphate (IMP) was found. Adenosine levels on the other hand did
      not increase. Hypoxanthine was the major end catabolite of ischemic lung tissue
      (constituting 92% of the nucleoside and purine base fraction at 4 hours
      ischemia). To further determine the pathway of AMP degradation, 400 mM of the
      adenosine deaminase inhibitor erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA) was
      added to the lung flush solution. During ischemia, adenosine triphosphate (ATP)
      breakdown was unaltered but adenosine became the major catabolite (2.8 times the
      concentration of hypoxanthine at 4 hours ischemia). These data suggest that: 1)
      in rabbit lung tissue, dephosphorylation of AMP to adenosine is more important
      than deamination to IMP; 2) hypoxanthine is the major end catabolite of ischemic
      lung tissue. By inhibiting the enzyme deaminase, reduced hypoxanthine levels and
      increased adenosine levels were obtained. Pharmacological interventions are now
      available to interfere with the formation of adenine nucleosides and bases in
      ischemic lung tissue. The importance of adenine nucleotide catabolites to
      postischemic lung reperfusion injury is discussed.

PMID- 7734435
TI  - Cerebrospinal fluid retrieval in the conscious dog: a methods development study.
AB  - A chronic cerebrospinal fluid access system is described for use in the conscious
      sling-restrained dog. In a pilot study of ten dogs, a fenestrated barium
      impregnated silastic catheter was surgically implanted in the subarachnoid space
      of the second cervical vertebra through a dorsal laminectomy. This fenestrated
      catheter was coupled to a subcutaneous access port. Following surgery,
      cerebrospinal fluid was sampled weekly and evaluated for protein content and
      cytology. The cerebrospinal fluid albumin to serum albumin ratio was calculated
      for each sample to evaluate blood-brain barrier integrity. The instrumentation
      was successfully implanted in five of the first eight dogs using a midbody dorsal
      laminectomy. Cerebrospinal fluid access was maintained in these dogs for 21 +/-
      10 days. Using a slight modification of the original technique, the final two
      dogs were instrumented through a caudodorsal laminectomy of the second cervical
      vertebra. The cerebrospinal fluid access system remains patent after 444 days of
      study in these two dogs. Necropsy evaluation suggested that catheter failure in
      the immediate postoperative period was due to gross malposition of the catheter.
      Chronic catheter failure occurred secondary to obstruction by local fibrous
      tissue reaction. Using this instrumentation, a pharmacokinetic evaluation of the
      plasma and cerebrospinal fluid deposition of an intravenous bolus of acyclovir
      was successfully performed twice in a single dog without complications. This
      instrumentation could provide chronic cerebrospinal fluid access for multiple
      pharmacokinetic studies in the conscious dog.

PMID- 7734436
TI  - Hemodynamic changes in blood flow through the denervated liver in pigs.
AB  - We investigated the effects of liver denervation on hemodynamic circulation in
      seven anesthetized pigs. Simultaneous measurements of the hepatic artery and
      portal vein were performed with an ultrasound Doppler flow meter before and after
      liver denervation. Neither resting systemic nor hepatic hemodynamics changed
      following liver denervation. However, temporary occlusion of the portal vein
      resulted in a significant increase in hepatic artery flow in the innervated liver
      (from 123 +/- 15 ml/min to 177 +/- 17 ml/min, p < .01), whereas, in the
      denervated liver, a significant decrease was observed (from 128 +/- 11 ml/min to
      106 +/- 19 ml/min, p < .05). Thus, the reciprocity between the hepatic artery and
      portal vein in the hepatic artery flow during portal vein occlusion might
      intensify symptoms of portal vein thrombosis in liver transplantation. In the
      denervated liver, a significant decrease also occurred in systolic blood pressure
      and central venous pressure from 1 to 3 min after portal vein occlusion. Since
      the liver plays a crucial role in the maintenance of cardiovascular homeostasis
      during blood loss, it is likely that denervation at the porta hepatis induced a
      lack of vasoconstriction in the portal territory. Liver denervation might further
      exacerbate this response to hypotension. The current study confirms that the
      hepatic nerves play an important role in hepatic arterial and portal venous
      interactions aimed at maintaining a constant blood flow through the liver. We
      also suggest that the hepatic nerves are important for cardiovascular
      homeostasis.

PMID- 7734437
TI  - Phases and phase transitions of the sphingolipids.
AB  - LIPIDAT is a computerized database providing access to the wealth of information
      scattered throughout the literature concerning synthetic and biologically derived
      polar lipid polymorphic and mesomorphic phase behavior. Herein, we present a
      review of the LIPIDAT data subset referring to sphingolipids together with an
      analysis of these data. It includes data collected over a 40-year period and
      consists of 867 records obtained from 112 articles in 25 different journals. An
      analysis of these data has allowed us to identify trends in hydrated sphingolipid
      phase behavior reflecting differences in fatty acyl chain length, saturation and
      hydroxylation, head group type, and sphingoid base identity. Information on the
      mesomorphism of biologically-derived and dry sphingolipids is also presented.
      This review includes 161 references.

PMID- 7734438
TI  - Triacylglycerol biosynthetic enzymes in lean and obese Zucker rats.
AB  - In the present investigation, we have compared the potential of triacylglycerol
      formation from sn-glycerol-3-phosphate (GP) and 2-monoacylglycerol (MG) in liver,
      adipose tissue and intestine from lean and obese Zucker rats. Microsomal
      fractions were used to measure the sn-glycerol-3-phosphate acyltransferase
      (GPAT), diacylglycerol acyltransferase (DGAT) and monoacylglycerol
      acyltransferase (MGAT) activities and homogenates were used to measure NEM
      sensitive and NEM-insensitive phosphatidate phosphohydrolase (PPH) activities. In
      adipose tissue and liver, the GP pathway served as the major route of
      glycerolipid formation, with adipose tissue being 5-20-fold more active. The
      activities of the GP pathway enzymes increased further in response to obesity,
      with some degree of organ specificity. In adipose tissue of obese rats, the
      activities of all the pathway enzymes increased; whereas, in liver and intestine,
      this response was limited to PPH and GPAT, respectively. In contrast with the GP
      pathway enzymes, obesity in Zucker rats was not associated with alterations in
      the acylation of 2-monoacylglycerol. Comparison of the activities of MGAT in
      different intestinal segments indicated that the MG pathway was most active in
      the jejunum and least active in the ileum and that this pattern did not change in
      response to obesity. These measurements of the individual enzyme reactions
      provide evidence that the entire process of esterification via sn-glycerol-3
      phosphate is accelerated in the various organs from obese rats and that this
      perturbation in lipid metabolism may contribute significantly to the increased
      deposition of body fat noted in this animal model.

PMID- 7734439
TI  - On the rate-limiting step in the beta-oxidation of polyunsaturated fatty acids in
      the heart.
AB  - This study was conducted to determine if the activity of 2,4-dienoyl-CoA
      reductase limits the rate of cardiac beta-oxidation of highly unsaturated fatty
      acids. Although growth hormone treatment of hypophysectomized rats caused a 3
      fold increase in the activity of 2,4-dienoyl-CoA reductase, beta-oxidation of
      docosahexaenoate in cardiomyocytes was not stimulated by this treatment. Since
      cardiomyocytes oxidized oleic acid more rapidly than docosahexaenoic acid, the
      utilization of energy did not limit beta-oxidation. Respiration measurements with
      coupled rat heart mitochondria revealed that the rates of beta-oxidation with
      palmitoyl-CoA and palmitoylcarnitine as substrates were virtually identical but
      were 3- to 4-fold higher than the rates obtained with either docosahexaenoyl-CoA
      or docosahexaenoylcarnitine. Although the activity of carnitine
      palmitoyltransferase I (CPT I) was 5 times higher with palmitoyl-CoA as substrate
      than with docosahexaenoyl-CoA, this reaction is only one of several that may
      limit the beta-oxidation of docosahexaenoic acid. Surprisingly, an incremental
      inhibition of CPT I resulted in a parallel inhibition of respiration supported by
      either palmitoyl-CoA or docosahexaenoyl-CoA. This observation agrees with the
      notion that CPT I may also be a regulatory enzyme in cardiac fatty acid
      oxidation. It is concluded that the reduction of double bonds by 2,4-dienoyl-CoA
      reductase does not restrict the cardiac beta-oxidation of highly unsaturated
      fatty acid, like docosahexaenoic acid.

PMID- 7734440
TI  - On the surface activity of surfactant-associated protein C (SP-C): effects of
      palmitoylation and pH.
AB  - The effect of palmitoylation on the surface activity of bovine surfactant
      associated protein C (SP-C) in lipid mixtures was investigated. Native and
      chemically depalmitoylated SP-C were reconstituted with
      dipalmitoylphosphatidylcholine/egg phosphatidylglycerol (7:3) using two different
      procedures, one of which included lyophilization and sonication. When tested
      using a pulsating bubble surfactometer, no significant changes in the surface
      activity of these mixtures were observed upon the hydrolysis of the palmitates.
      Since the purification and deacylation procedures of SP-C included the use of
      acid and alkali, the effect of pH was examined. The surface activity of the
      mixtures was found to vary with pH. At low pH values (approx. 2.5), surface
      tensions between 3 and 10 mN/m at minimum bubble radius were reached within 5
      pulsations, while at neutral and slightly alkaline pH, surface tension reduction
      was much slower and near zero (< 5 mN/m) values at minimum bubble radius were not
      reached by the fiftieth pulsation. Protein-free lipid samples that were exposed
      to acid exhibited enhanced surface activity over similar non-treated samples. It
      is therefore concluded that low surface tension measurements recorded for acidic
      samples are secondary to a pH effect and do not reflect the surface activity at
      physiological conditions.

PMID- 7734441
TI  - Interconversions and distinct metabolic fate of eicosapentaenoic,
      docosapentaenoic and docosahexaenoic acids in bovine aortic endothelial cells.
AB  - The anti-aggregatory activity of endothelial cells being affected by
      eicosapentaenoic (EPA, 20:5(n-3)) and docosahexaenoic (DHA, 22:6(n-3)) acids, the
      two main polyunsaturated fatty acids of fish oil, these fatty acids, as well as
      their intermediary, docosapentaenoic acid (DPA, 22:5(n-3)), were investigated
      with respect to their metabolism. Primary cultured bovine aortic endothelial
      cells were supplemented for 22 h at 37 degrees C with either n-3 fatty acid, and
      the fatty acids of cell media, of cell lipid classes, and of choline and
      ethanolamine glycerophospholipids (PC and PE) were quantified. Endothelial cells
      converted each of the three fatty acids into the two others. They were found
      esterified in cell lipids and partly released in cell media, the respective parts
      varying according to the fatty acid. For instance, half of the DPA formed from
      EPA and two third of the EPA formed from DPA were released in the media.
      Moreover, the DHA formed from EPA and DPA was not esterified but released in
      media. In addition, the esterified counterparts were found in either PC or PE,
      depending on whether they were added or formed by conversions. It is concluded
      that EPA, DPA and DHA are actively interconverted each others, and differ
      substantially in terms of distribution between media and cells, and within
      phospholipid classes.

PMID- 7734442
TI  - Regulation of lecithin:cholesterol acyltransferase by TGF-beta and interleukin-6.
AB  - The human hepatoma derived HepG2 cells were treated with transforming growth
      factor-beta (TGF-beta) or interleukin-6 (IL-6) +/- dexamethasone. The effects of
      treatment on lecithin:cholesterol acyltransferase (LCAT) catalytic activity and
      mRNA level as well as on the apolipoprotein A-I (apo A-I) mRNA level were
      determined. Both the LCAT activity in medium from treated HepG2 cells and the
      LCAT mRNA level were decreased by TGF-beta. There was no significant effect of IL
      6 +/- dexamethasone, neither on the LCAT activity nor on LCAT mRNA levels.
      Treatment with dexamethasone alone resulted in a decreased LCAT activity in spite
      of a slight increase in LCAT mRNA level. The apo A-I mRNA level was reduced after
      treatment with TGF-beta and increased after treatment with IL-6 +/- dexamethasone
      and dexamethasone alone. To analyze if the effects on mRNA levels were caused by
      transcriptional or post-transcriptional mechanisms, run-on experiments on
      isolated nuclei from treated HepG2 cells and mRNA degradation experiments were
      performed. The transcription rate of the LCAT gene was not affected by TGF-beta,
      but was increased (50-100%) after treatment with IL-6 +/- dexamethasone and
      dexamethasone alone. The transcription rate of the apo A-I gene was reduced (20%)
      by TGF-beta and increased (30-60%) by IL-6 +/- dexamethasone and dexamethasone
      alone. Both dexamethasone and TGF-beta increased the rate of LCAT mRNA
      degradation. These results show that the reduced LCAT mRNA level after treatment
      with TGF-beta was caused by post-transcriptional mechanisms.

PMID- 7734443
TI  - Purification and properties of two phospholipases D from Streptomyces sp.
AB  - Two enzymes with phospholipase D activity were purified from Streptomyces strains
      (PMF and PM43) by column chromatography on Fractogel TSK CM-650(S), Sephadex G
      100 and Fractogel EMD DEAE-650(M). The purified preparations were found to be
      homogeneous by SDS-PAGE, capillary electrophoresis and analytical gel filtration.
      The molecular masses, assessed by MALDI-MS spectrometry, were 53.864 kDa for PMF
      and 54.147 kDa for PM43. The isoelectric point was 9.1 for both enzymes. The
      enzymes were most active at around 60 degrees C and stable between pH 4 and 9 and
      below 50 degrees C. The pH optima were between 4 and 6 for PMF and between 6 and
      7 for PM43. Both phospholipases displayed high transphosphatidylation activity
      but PMF was more selective than PM43.

PMID- 7734444
TI  - Free ceramides of Echinococcus multilocularis metacestodes.
AB  - Free ceramides were isolated and purified from the metacestodes of Echinococcus
      multilocularis. Two different fractions were obtained by preparative thin-layer
      chromatography. Their structure was determined by gas chromatography and electron
      impact mass spectrometry of trimethylsilylated derivatives. The ceramide with the
      higher thin-layer chromatographic migration rate contained exclusively erythro
      sphinganine associated with saturated C16, C18 and very-long-chain fatty acids
      (up to C30) and unsaturated C24 fatty acid. The second ceramide contained 90.3%
      sphingosine and 9.7% sphinganine associated with saturated C16 and C24 and
      unsaturated C18 and C24 fatty acids. These findings were discussed with regard to
      the structure and metabolic pathway of neutral and acid glycosphingolipids found
      in the metacestodes.

PMID- 7734445
TI  - Abnormal structure and co-operative binding of low-density lipoprotein receptors
      containing the Glu-80-->Lys mutation.
AB  - The properties of low-density lipoprotein (LDL) receptors containing a Glu to Lys
      substitution at position 80 have been studied in fibroblasts from a homozygous
      familial hypercholesterolaemic subject (MB) and in monkey COS cells transfected
      with the mutant cDNA. Receptors containing the Glu-80-->Lys mutation were
      processed more slowly than the normal protein and only approx. 50% reached the
      surface as the mature form. Both cell types exhibited a normal concentration
      binding curve for beta-very-low-density lipoproteins (beta-VLDL) but an atypical,
      sigmoidal curve for LDL. The mature mutant receptor protein migrated abnormally
      slowly on SDS-PAGE under non-reducing conditions but normally under reducing
      conditions or after treatment with neuraminidase. It also showed an unusual
      ability to form dimers that were stable in detergents. Transfected normal and
      mutant receptors were apparently cleaved on the surface of the cells to give a
      product lacking the NH2-terminal portion of the protein, which was resistant to
      further proteolytic digestion. The results suggest that the Glu-80-->Lys
      substitution produces a change in the conformation of the protein, stabilized by
      polysaccharide chains, which results in a strong self-association of receptor
      molecules that affects their ability to bind LDL.

PMID- 7734446
TI  - Regulation of hepatic cholesterol metabolism in the rat in vivo: effect of a
      synthetic fat-free diet on sterol synthesis and low-density lipoprotein
      transport.
AB  - A synthetic fat-free diet, previously shown to decrease hepatic cholesterol
      synthesis, was utilized to manipulate cholesterol balance in vivo in female
      Sprague-Dawley rats. A significant 65% decrease of hepatic cholesterol synthesis
      compared to controls was shown after 1 week of treatment, which remained constant
      during the following 3 weeks. The inhibitory effect of the diet was completely
      abolished by cholestyramine supplementation. At week 3 of the experimental diet,
      bile acid synthesis was reduced by 63%, this reduction being correlated with
      decreased recycling frequency of the bile acid pool. Hepatic clearance of low
      density lipoprotein (LDL) was slightly decreased, with no changes in plasma
      cholesterol, hepatic LDL-cholesterol uptake and whole body LDL-cholesterol
      production. When cholesterol and saturated fatty acids were supplemented to the
      diets in the attempt to disclose alteration in LDL transport, LDL clearance was
      unaffected; plasma LDL-cholesterol and hepatic LDL-cholesterol uptake were
      increased, as a consequence of increased LDL-cholesterol production. On the other
      hand, hepatic cholesterol synthesis was further suppressed; bile acid synthesis
      was increased by cholesterol supplementation in the fat-free group, even if to
      subnormal levels. These findings suggest that: (1) bile acid synthesis is
      decreased by feeding a synthetic fat-free diet, probably due to slower
      recirculation of bile acids along the entero-hepatic axis in conditions of
      reduced functional need; (2) consequently, a significant reduction of hepatic
      cholesterol synthesis is observed with no changes in LDL-cholesterol uptake; (3)
      further supplementation of dietary cholesterol and saturated fats is compensated
      for by changes in the rates of cholesterol and bile acid synthesis, but not of
      LDL transport. The data confirm the existence of independent regulation for
      hepatic sterol synthesis and LDL transport in this species.

PMID- 7734447
TI  - Remodelling of lipoproteins in transgenic mice expressing human cholesteryl ester
      transfer protein.
AB  - Cholesteryl ester transfer protein (CETP) facilitates the transfer of reciprocal
      exchange of neutral lipids between lipoproteins. To better understand the
      function of CETP and its role in atherogenic pathways, transgenic mice which
      express human CETP were generated. The transgene encoding human CETP was under
      the control of the mouse alpha-fetoprotein enhancer and mouse albumin gene
      promoter and was expressed exclusively in the liver. The level of human CETP
      activity in transgenic mouse plasmas was found to be 1- to 5-fold greater than in
      normolipidemic human plasma. Human CETP induced an approx. 30 and 40% reduction
      of HDL cholesterol levels in plasma from female and male transgenic mice,
      respectively, when compared to controls. In addition, multiple alterations in
      mouse lipoprotein composition were observed in the transgenic mice. Diminished
      HDL cholesterol levels and disappearance of the apo E-rich HDL1 moiety account
      for the dramatic reduction in plasma cholesterol. The decrease in HDL cholesterol
      was accompanied by a marked reduction in HDL particle size and apo A-I content.
      The cholesterol content and the size of LDL particles increased, but only
      modestly, in transgenic mouse plasma. In conclusion, human CETP induces a
      significant remodelling of mouse lipoproteins which results in dramatic reduction
      in plasma cholesterol levels.

PMID- 7734448
TI  - Endogenous sulfidopeptide leukotriene synthesis and 12-lipoxygenase activity in
      bullfrog (Rana catesbeiana) erythrocytes.
AB  - Endogenous leukotriene (LT) synthesis by mammalian inflammatory cells requires
      both 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein. Other myeloid
      cells, like erythrocytes, have an incomplete 5-lipoxygenase pathway and
      synthesize leukotrienes transcellularly. Several studies indicate that
      sulfidopeptide leukotrienes have important physiological functions in bullfrogs
      and receptors have been characterized. Calcium ionophore activated bullfrog blood
      was analyzed by reverse phase-high-performance liquid chromatography (RP-HPLC).
      Endogenous metabolites consisted of 5-LO products including leukotriene D4. Other
      metabolites also suggested 12-lipoxygenase activity. Following purification,
      metabolites from activated erythrocytes were analyzed by RP-HPLC coupled with
      radioimmunoassay. Erythrocytes demonstrated endogenous synthesis of LTD4 which
      was inhibited by non-selective (NDGA) and specific (MK886) 5-lipoxygenase
      inhibitors. Experiments with partially purified erythrocyte cytosol further
      confirmed 5-LO activity and revealed 12-lipoxygenase activity. HPLC analysis of
      [1-14C]arachidonic acid labeled metabolites from activated erythrocytes indicates
      that most of the available substrate is converted to 12-hydroxy-eicosatetraenoic
      acid (12-HETE). These novel findings indicate that, in contrast to mammals,
      bullfrog erythrocytes endogenously synthesize LTD4 and large quantities of 12
      HETE giving them the potential to contribute directly to inflammatory responses.
      The evolutionary loss of the nucleus in mammalian erythrocytes appears to be
      associated with the inability to synthesize leukotrienes endogenously.

PMID- 7734449
TI  - Progesterone stimulation of HMG-CoA reductase activity in cultured cells.
AB  - In a previous study we showed that progesterone (PG) stimulated HMG-CoA reductase
      (HMGR) activity in rat intestinal epithelial cells (IEC-6) incubated in the
      presence or absence of low-density lipoprotein (LDL) [1,2]. In the present study
      we examined further the mechanism of this stimulation. We observed that the
      stimulation of HMGR activity by PG was completely prevented by cycloheximide.
      Turnover studies utilizing immunoprecipitation of HMGR-labeled with
      [35S]methionine revealed that PG increased reductase activity by inhibiting HMGR
      degradation without affecting the synthesis of HMGR. The stimulation of HMGR
      activity by progesterone could be accounted for by a continuous synthesis of HMGR
      while its degradation was retarded. In the presence of LDL, the activity of HMGR
      in IEC-6 cells was effectively inhibited, however PG was able to stimulate HMGR
      in the presence of LDL. This effect was not due to an interference of normal
      cellular metabolism of LDL, since PG had no effect on the cellular uptake and
      lysosomal degradation of 125I-LDL. PG did not affect of the rate of lysosomal
      hydrolysis of [3H]cholesteryl linoleate-LDL. The free [3H]cholesterol derived
      from [3H]cholesteryl linoleate-LDL moved to the cell membrane and effluxed to
      HDL3 in the medium at the same rate in the presence or absence of PG. Although PG
      did not affect LDL metabolism, pre-treatment of cells with LDL delayed the onset
      of HMGR stimulation by PG. In IEC-6 cells deprived of LDL for 24 h, the HMGR
      activity was stimulated immediately following PG addition. In cells pre-treated
      with LDL for 24 h, the stimulation was delayed by 4 h. Treatment of cells with 25
      hydroxycholesterol completely prevented PG stimulation of HMGR activity. We
      propose that the stimulation of HMGR activity in the presence or absence of LDL
      is related to the ability of PG to attenuate the formation and/or action of
      intracellular HMGR repressor molecules which accelerate the degradation of HMGR.

PMID- 7734450
TI  - Influence of cell culture conditions on diet-induced changes in lymphocyte fatty
      acid composition.
AB  - The effect of a range of dietary lipids on the fatty acid composition and
      membrane fluidity of lymphocytes was investigated. The effects of subsequent
      culture of these lymphocytes in medium containing autologous serum, foetal calf
      serum or a serum-free supplement were assessed; this was considered important,
      since many studies investigating the effects of dietary lipid manipulation on
      immune function have used protocols involving a variety of cell culture
      conditions when performing tests of immune function. Weanling Lewis rats were fed
      for 10 weeks on a low-fat (LF; 20 g/kg) diet or on high fat diets containing 200
      g/kg of either hydrogenated coconut oil (HCO), olive oil (OO), safflower oil
      (SO), evening primrose oil (EPO) or menhaden oil (MO). The fatty acid composition
      of the phospholipid fractions of lymphocytes from the spleen was altered by
      dietary lipid manipulation, whereas the fatty acid composition of thymic
      lymphocytes was not modified significantly. In general, the changes in the fatty
      acid composition of spleen lymphocytes reflected the fatty acid composition of
      the diets themselves. Despite the considerable changes in the fatty acid
      composition of lymphocytes from spleen, dietary lipid manipulation had no effect
      on the plasma membrane fluidity of these cells. Culturing lymphocytes in
      autologous serum allowed some, but not all, of the diet-induced changes in fatty
      acid composition to be maintained. The effects of dietary lipid manipulation were
      totally reversed when lymphocytes were cultured in FCS. Culturing lymphocytes in
      serum-free medium not only reversed any effects of dietary manipulation, but also
      markedly increased the appearance of palmitoleic and oleic acids, at the expense
      of palmitic and stearic acids, suggesting activation of the delta 9 desaturase
      when these cells were cultured in the absence of exogenous lipid. This study
      suggests that cell culture conditions have significant influence on the changes
      in lymphocyte fatty acid composition brought about by dietary lipid manipulation
      and may therefore influence the outcome of functional tests.

PMID- 7734451
TI  - Cholest-3,5-dien-7-one formation in peroxidized human plasma as an indicator of
      lipoprotein cholesterol peroxidation potential.
AB  - Lipoprotein peroxidation susceptibility is routinely evaluated using products of
      unsaturated fatty acids as markers (e.g., malonaldehyde). The significance and
      factors influencing peroxidation of cholesterol moiety of lipoproteins are
      relatively unknown due to lack of a reliable marker product which can be measured
      easily. Under the influence of Cu2+ ions, the major product of lipoprotein
      cholesterol peroxidation (isolated after saponification) was cholest-3-5-dien-7
      one (CSD). Apart from gas-liquid chromatography, this compound lends itself for
      measurement by alternative methods. Due to lack of the 3 beta-hydroxyl group, CSD
      was separated from the rest of the oxysterols and cholesterol by passing through
      digitonin-coated silica-gel G and its concentration was determined by absorption
      at 283 nm. The recovery of CSD by this method exceeded by 87%. The formation of
      CSD was also sensitive to vitamin E and therefore could be used as an index of
      lipoprotein cholesterol susceptibility to peroxidation.

PMID- 7734452
TI  - Cloning and characterization of the mouse PIG-A gene.
AB  - Currently there is no experimental animal model for studying paroxysmal nocturnal
      hemoglobinuria (PNH), an acquired hemolytic anemia linked to mutations of the PIG
      A gene. In this study, we cloned and characterized the mouse PIG-A gene.
      Sequencing of mouse PIG-A cDNA showed that it encodes a 485 amino acid-long
      protein. Northern hybridizations identified a major mRNA transcript of 3.6 kb and
      PCR amplifications identified four smaller alternative splice products.
      Exon:intron junctional analyses of the mouse PIG-A genome showed 6 exons (1(> or
      = 60 bp), 2(780 bp), 3(133 bp) 4(133 bp), 5(207 bp), and 6(2276 bp)), the latter
      5 of which encompass the coding region. Chromosomal mapping using C57BL/6J x M.
      Spretus backcross DNA localized the mouse PIG-A gene near the telomeric end of
      the mouse X chromosome. The isolation of the mouse PIG-A gene opens the
      possibility for the development of a mouse model of PNH.

PMID- 7734453
TI  - Lipoxygenase activity in rat dermis and epidermis: partial purification and
      characterization.
AB  - Lipoxygenase (LOX) activity in epidermis and dermis was distributed among
      microsomal and cytosolic fractions. The main products of polyunsaturated fatty
      acid metabolism were 12-hydroperoxy-cis-5,8,14, trans-10-eicosatetraenoic acid
      (12-HPETE), 15-hydroperoxy-cis-5,8,11, trans-13-eicosatetraenoic acid (15-HPETE)
      and 13-hydroxy-cis-9, trans-11-octadecadienoic acid (13-HOD). Enzyme activities
      were isolated from rat dermis and epidermis by ammonium sulphate precipitation,
      hydrophobic chromatography and gel filtration. In the dermis, activity was found
      at a molecular mass of 68 kDa, a pI of 4.6 and a Km of 50 microM. This activity
      was inhibited by known LOX inhibitors. The main reaction products indicated that
      this was 15-LOX. In the epidermis, activity was found in a fraction with a
      molecular mass of 68 kDa, a pI of 4.6 and a Km of 80 microM. Activity was
      inhibited by known LOX inhibitors whereas the reaction products indicated that
      this was 12-LOX. LOX activity in rat skin may involve one enzyme with dual
      regional specificities or may comprise two different enzymes.

PMID- 7734454
TI  - Integrating treatment innovation and research: the NIDA Experimental Therapeutics
      Program (Part I)

PMID- 7734455
TI  - Psychiatric disorders of opioid addicts entering treatment: preliminary data.
AB  - Psychiatric disorders have become an increasing concern in the treatment of
      substance abusers. The introduction of the Human Immunodeficiency Virus (HIV)
      into this population has further complicated treatment. This study examines the
      prevalence of psychiatric disorders in an opioid dependent population maintained
      on methadone. Results from this preliminary analysis show high rates of
      psychiatric disorders in this population. Additionally, needle sharing behavior
      appears to be increased in patients with a diagnosis of dysthymia. These findings
      have direct implications for aggressive screening and treatment of psychiatric
      disorders in methadone maintenance clinics.

PMID- 7734456
TI  - Antidepressant treatment in methadone maintenance patients.
AB  - We review the controlled trials of antidepressant treatment in methadone
      patients. Several studies show antidepressant effects, but none demonstrate clear
      improvement in drug abuse. This is contrary to "self-medication" but rather
      suggests depression is either independent or substance induced. Methodologic
      limitations are noted, especially reliance on cross-sectional mood assessment,
      which may select transient mood disturbances rather than true affective disorder.
      We review our previously published pilot study of imipramine in depressed
      methadone patients selected by lifetime history, and we report four year
      treatment course in the nine patients who responded favorably during that trial.
      Patients remained euthymic during imipramine treatment and relapsed to depression
      during attempts to taper it. This suggests imipramine had an enduring
      antidepressant effect. However, intermittent drug use remained a problem for
      several patients, suggesting depression and drug abuse are at least in part
      independent disorders. Placebo controlled replications, combinations of
      antidepressant medication with psychosocial interventions, and exploration of
      antidepressants as adjuncts in methadone detoxification, are suggested avenues
      for further research.

PMID- 7734457
TI  - Fluoxetine treatment for dually diagnosed methadone maintained opioid addicts: a
      pilot study.
AB  - Twenty-two methadone maintained opioid addicts with either depression or
      persistent cocaine use received open label fluoxetine in addition to their
      methadone. Fluoxetine significantly decreased depressive symptoms from pre
      treatment to endpoint in subjects with depression, while its effect on substance
      use was inconclusive.

PMID- 7734458
TI  - A preliminary investigation of outcome following gradual or rapid buprenorphine
      detoxification.
AB  - Eight opioid-dependent individuals were maintained on daily sublingual
      buprenorphine (8 mg) for 28 days and assigned randomly to one of two outpatient
      detoxification schedules under double-blind, double-dummy conditions. The two
      detoxification schedules were buprenorphine gradual (36 days; N = 3) or
      buprenorphine rapid (12 days; N = 5). Outcome variables were subject- and
      observer-ratings of opioid withdrawal, treatment retention and illicit-opioid
      use. Outcome measures were similar for the two groups during buprenorphine
      maintenance. Increases in subject-rated opioid withdrawal and illicit-opioid use,
      and a drop in treatment retention occurred during rapid detoxification. Stable
      subject-rated opioid withdrawal and treatment retention, and less illicit-opioid
      use occurred during gradual detoxification. These data suggest that gradual
      reduction in buprenorphine dose is likely to produce superior treatment outcomes
      than more rapid buprenorphine detoxification.

PMID- 7734459
TI  - Contingency management of urinalysis results and intensity of counseling services
      have an interactive impact on methadone maintenance treatment outcome.
AB  - In a 3 x 2 factorial design, 360 new admissions to methadone maintenance were
      randomly assigned to one of three levels of counseling: (1) "medication only,"
      (2) "standard" counseling, and (3) "enhanced" services; and one of two
      contingency contracting conditions: (1) no contingencies (NC), and (2)
      contingency contracting (CC). Contingency contracting included discharge for
      continuous positive urines; subsequently CC subjects were discharged at a greater
      rate than the NC group. However, CC subjects were more likely to be readmitted.
      NC subjects provided more urines positive for any illicit drug use than did CC
      subjects. For opiate positives a significant level of counseling by contingency
      contracting interaction was found with medication only/CC subjects obtaining
      fewer opiate positives than medication only/NC subjects. The impact of reduced or
      enhanced services and of contingency contracting will not be fully understood
      until longer term follow-up (18 and 24 month) is completed. Results suggest that
      contingency management procedures could be utilized in settings offering minimum
      services (e.g., "interim methadone") to achieve treatment outcomes similar to
      programs offering standard counseling services.

PMID- 7734460
TI  - Medical maintenance: an interim report.
AB  - In a pilot study, 130 methadone maintained subjects with a six-month history of
      good treatment performance were assigned randomly, for a one-year study period,
      to an experimental condition (once per month non-random urine screen, counseling
      session and doctor visit, two times per month methadone pick up, a quarterly true
      random urine screen, and participation in a diversion control program), or they
      were assigned to a control condition of staying under standard conditions for six
      months and then being transferred to the experimental condition for six months.
      Three out of four subjects (73%) completed the year in good standing with no
      differences between control and experimental conditions. Subject satisfaction was
      such that the Institutional Review Board judged that return to standard
      conditions would be a hardship. A Study of Medical Maintenance (SMM) continues
      and extends the pilot study with two protocols: (1) for new subjects and (2) for
      subjects entered from the pilot study. SMM requires a once per month random urine
      screen and extends the experimental condition to two years but is otherwise
      identical to the pilot study; 71 of 107 S's (66%) entered protocol 1 and are in
      good standing. Pilot subjects (N = 75) are holding their good performance, some
      for over four years. The reduced levels of services in these studies free up
      resources which can be applied to entering IDU's into treatment thereby
      contributing to a slowing of the HIV epidemic.

PMID- 7734461
TI  - The impact of the addition of an acupuncture treatment program to an existing
      metro-Dade County outpatient substance abuse treatment facility.
AB  - There are several varieties of treatment facilities and modalities for dealing
      with substance abuse. In this study, the addition of acupuncture treatments to
      the usual care program at an existing county-based substance abuse treatment
      clinic was tested. Men and women who voluntarily attended the clinic or who were
      remanded by the court to attend were randomized to receive usual care, usual care
      plus frequent urine testing, or usual care plus frequent urine testing and
      acupuncture treatments. Clients who received acupuncture treatments in addition
      to the usual care and frequent urine testing became clean (as measured by
      negative urine tests) in 57% of the time required for the frequent urine testing
      group. Difficulties experienced included low counselor compliance with the
      protocol and a high drop-out rate, indicating that further research is necessary;
      however, this study demonstrates that acupuncture can be a feasible and effective
      addition to existing drug treatment programs.

PMID- 7734462
TI  - Integrating treatment innovation and research: the NIDA Experimental Therapeutics
      Program (Part II)

PMID- 7734463
TI  - Comparative cocaine abuse treatment strategies: enhancing client retention and
      treatment exposure.
AB  - The current investigation explores the clinical utility in providing a series of
      enhanced clinical services to a sample of 303 cocaine-abusing clients (primarily
      crack smokers) relative to a standard group therapy treatment program. In
      addition to examining the comparative impact of six varying psychosocial
      treatment approaches for cocaine abuse on client retention and treatment exposure
      rates, an additional emphasis has been to examine the ability of fixed and
      dynamic client variables in predicting client outcome in this regard. No fixed
      (e.g., sex, income, marital status, income level, or employment status) or
      dynamic (e.g., recent alcohol use, antisocial personality disorder diagnoses, or
      motivational variables) client characteristics were useful in predicting client
      retention or treatment exposure rates. Program characteristics, however, or the
      frequency, intensity, and/or type of treatment services offered, were related to
      client retention and treatment exposure. Treatment exposure and retention were
      significantly enhanced by providing clients with more frequent and intensive
      group therapy, or by adding individual treatment services to a standard group
      therapy treatment regimen. With a population such as cocaine abusers, who
      typically have an extremely high treatment dropout rate, an obvious strategy is
      to focus efforts on engaging and retaining clients in treatment, and maximizing
      levels of treatment exposure. The current findings suggest that one successful
      approach towards enhancing psychosocial treatments for cocaine abuse is to
      increase the frequency, intensity, and/or types of treatment services offered.

PMID- 7734464
TI  - The Matrix model of outpatient stimulant abuse treatment: evidence of efficacy.
AB  - The current study examined the effectiveness of Matrix outpatient stimulant
      treatment. We associated 146 subjects' in-treatment abstinence data, treatment
      lengths, and weekly treatment activities to their 6-month abstinence outcomes as
      part of an interim analysis of a NIDA treatment demonstration project. Results
      indicated that the pretreatment subject characteristics of ethnicity and drug of
      choice significantly associated with treatment outcome using Matrix model
      treatment. Findings also demonstrated a treatment dose/abstinence response such
      that those who received longer Matrix treatment episodes demonstrated better
      abstinence outcomes. Further, in-treatment abstinence status and treatment length
      significantly associated with drug use status at follow-up. This set of findings
      provides evidence for the value of Matrix treatment and allows for these outcome
      data to be compared with reports on recent psychosocial treatments for stimulant
      dependence. This study also provides direction for evaluating longer term
      effectiveness for these types of drug treatments.

PMID- 7734465
TI  - Neurobehavioral treatment for cocaine-using methadone patients: a preliminary
      report.
AB  - Preliminary outcome evaluation results are reported for an innovative cocaine
      abuse treatment model adapted for cocaine-using methadone patients. Sixty-two
      patients were randomly assigned to six months of high intensity
      ("neurobehavioral") or lower intensity ("control") therapy for cocaine
      dependence. Therapy was completed by 49% of neurobehavioral and 53% of control
      patients. In paired comparisons between intake and six-month follow-up,
      neurobehavioral patients but not controls showed significant declines in cocaine
      and other drug use (measured by urinalysis and self-reports), as well as
      significant improvement in psychological status. The findings suggest that
      specialized cocaine abuse treatment can benefit methadone patients; intake to the
      study is continuing.

PMID- 7734466
TI  - The effect of a no-smoking policy on recruitment and retention in outpatient
      cocaine treatment.
AB  - Historically, directors of substance abuse treatment programs have been reluctant
      to adopt a smoke-free policy because of the fear of patient attrition. According
      to a recent survey, however, a number of program directors now believe that such
      fears may be unwarranted. The purpose of the present study was to examine the
      impact on admissions and attendance of adopting a smoke-free policy at a cocaine
      treatment program offering outpatient group therapy sessions 3 half days a week.
      Results indicated that implementation of this policy had no impact on the number
      of patients who sought treatment at the facility or the number of group sessions
      patients attended. It was also noteworthy that for a sample of cases active in
      the month prior to and the month following the ban there were no changes in
      attendance patterns or in the proportion of patients failing to return from a 10
      15 minute therapy break despite the fact that 89% of these patients were
      cigarette smokers.

PMID- 7734467
TI  - Therapist/patient matching and early treatment dropout.
AB  - This study of intake procedures was initiated with a view towards reducing the
      early dropout rate of substance abusers. Eight different therapists conducted
      intake interviews of 634 cocaine dependent, first admissions to an outpatient
      cocaine treatment program. No significant differences in return rate were found
      across either the eight therapists or their level of academic training. We found
      that matching therapists and patients with respect to gender and race for the
      intake interview did not increase the proportion of patients returning for a
      second visit. In addition, the hypothesis that providing a sense of continuity by
      having the therapist who conducted the intake interview become the treatment
      therapist did not result in a higher return rate than if the patient was assigned
      to a different treatment therapist. Although the results do not indicate methods
      of further reducing early treatment dropouts they are helpful in reducing
      concerns about who conducts intake interviews and how patients are assigned.

PMID- 7734468
TI  - Alcohol dependence and simultaneous cocaine and alcohol use in cocaine-dependent
      patients.
AB  - Alcohol use and associated factors were studied in 124 consecutive cocaine
      dependent admissions to an outpatient substance abuse clinic. Two analyses were
      conducted: First, those who did and did not meet criteria for current alcohol
      dependence were compared on sociodemographic and drug use characteristics.
      Second, patients who reported simultaneous cocaine and alcohol use on > 50% vs. <
      or = 50% of the occasions that they used cocaine were compared using the same
      dependent measures. Fifty-seven percent of patients met criteria for current
      alcohol dependence. Those with and without alcohol dependence did not differ on
      any sociodemographic characteristics, but those with dependence scored higher on
      the alcohol and family subscales of the Addiction Severity Index, the Michigan
      Alcoholism Screening Test, and measures of alcohol use, and were more likely to
      use cocaine and alcohol simultaneously, to use cocaine with friends and in social
      settings, and were more likely to report financial difficulties and unwanted
      sexual relations as adverse consequences of their cocaine use. Sixty-four percent
      of patients reported > 50% simultaneous cocaine and alcohol use. The two groups
      did not differ on any sociodemographic characteristics, but those reporting
      greater simultaneous use were more likely to be alcoholic, scored higher on most
      measures of alcohol use, and were more likely to report using cocaine with
      friends and in social settings. The only other differences observed between the
      two groups were fewer reports of seizures or difficulty concentrating in the
      group reporting greater simultaneous use. The present results confirm prior
      reports on the widespread prevalence of alcohol dependence among cocaine
      dependent patients and extend them by providing new information on the prevalence
      and other characteristics of simultaneous cocaine and alcohol use.

PMID- 7734469
TI  - Impact of desipramine or carbamazepine on patient retention in outpatient cocaine
      treatment: preliminary findings.
AB  - This is a preliminary report of a double-blind comparison of desipramine or
      carbamazepine to placebo among subjects participating in an outpatient cocaine
      treatment program. Sixty-five subjects were randomly assigned to one of the
      active drugs or placebo and followed until treatment completion or drop-out to
      determine if either drug enhanced retention in treatment and/or increased cocaine
      abstinence. There was no significant difference between carbamazepine or
      desipramine and placebo on either outcome measure in this preliminary analysis.
      While this is a preliminary report and does not take into account the
      heterogeneity of the patients in cocaine treatment, the results are consistent
      with those of other investigators and suggest that use of desipramine or
      carbamazepine may not offer any advantage in retaining cocaine-dependent patients
      in treatment.

PMID- 7734470
TI  - Imipramine for the treatment of cocaine and methamphetamine dependence.
AB  - At the Drug Detoxification, Rehabilitation, and Aftercare Program of the Haight
      Ashbury Free Clinics, we conducted a double-blind, controlled, randomized
      clinical trial of imipramine in the treatment of cocaine and methamphetamine
      abusers. The purpose of the trial was to test the efficacy of imipramine as a
      treatment for stimulant dependence and to establish the feasibility of conducting
      a controlled clinical trial at the clinic under conditions that approximated
      usual clinical practice. Subjects were randomly assigned to receive either 10 or
      150 mg/day of imipramine. Imipramine 10 mg/day was the control condition.
      Subjects could receive study medication for up to 180 days. One-hundred eighty
      three subjects participated in the study: 151 were cocaine dependent and 32 were
      methamphetamine dependent. In addition to receiving study medication, all
      subjects were assigned to intensive drug abuse counseling, which included an HIV
      education component. Using an intention-to-treat analysis, we found that
      retention in treatment was significantly longer for subjects who were treated
      with 150 mg of imipramine compared to control. However, we found no consistent
      differences between the two groups of subjects in Beck Depression Inventory
      scores, stimulant craving, self-report of time since last use of stimulants, or
      percent of urinalyses positive for stimulants. The feasibility of conducting a
      controlled, randomized clinical trial of medication for treatment of drug abuse
      was established for this community clinic setting.

PMID- 7734471
TI  - Public policy statement on national drug policy. American Society of Addiction
      Medicine.

PMID- 7734472
TI  - Public policy statement on persons with alcohol and other drug (AOD) problems and
      the criminal justice system. American Society of Addiction Medicine.

PMID- 7734473
TI  - Introduction: revisiting the sacred cows.

PMID- 7734474
TI  - Exercise tests as outcome measures.
AB  - Outcome assessments of physical fitness attributes such as endurance, strength,
      and flexibility are not measured routinely in clinical trials or clinical
      practice in either adults or children with rheumatic diseases. Although physical
      fitness is not a measure of disease severity, it can be a critical indicator of
      capacity to function. Adequate fitness is necessary for the performance of
      positive health behaviors that enhance health status and wellness in spite of
      chronic disease. The purpose of this paper is to explore the conceptual,
      methodologic, and analytic issues related to the use of exercise tests as outcome
      measurements of physical functioning in persons with rheumatic disease.

PMID- 7734475
TI  - The impact of fatigue on exercise performance.
AB  - The purpose of this paper is to discuss the impact of fatigue on exercise
      performance. First, fatigue will be defined and distinguished from similar
      constructs. Second, examples of instruments to measure fatigue in the rheumatic
      diseases are highlighted. Next, the social implications of fatigue are briefly
      mentioned. Fourth, methods in which fatigue impacts exercise performance are
      discussed. Fifth, the prevalence of fatigue in arthritis and its relationship to
      exercise will be presented. And last, areas of future research and roles of
      clinicians in managing fatigue relative to exercise performance are proposed.

PMID- 7734476
TI  - Promoting patient cooperation with exercise programs: linking research, theory,
      and practice.
AB  - Managing patient-nonadherence with prescribed exercise regimens is not an
      uncommon task for physical therapists working with individuals with arthritis.
      Yet little is known about the factors that influence patient adherence with
      exercise programs or therapist knowledge and use of theoretically based adherence
      management techniques. Survey research with physical therapists and patients was
      used to provide a database for further insight into the barriers experienced in
      implementing exercise programs in clinical practice. In this paper, we suggest
      that the cooperation with an exercise regimen is mediated by the patient's belief
      system and requires a therapeutic process of mutual inquiry, problem solving, and
      negotiation between the therapist and patient. Concepts from research, theory,
      and practice are integrated into a Process Model for Patient-Practitioner
      Collaboration for use in clinical practice.

PMID- 7734477
TI  - Therapeutic exercise in rheumatoid arthritis.
AB  - Although about 80% of individuals with rheumatoid arthritis [RA] are functionally
      independent on any given occasion [1], substantial functional disability is often
      observed over time in the average patient [2]. One important goal in
      rehabilitation of individuals with RA is the prevention of functional decline,
      and therapeutic exercise is frequently used for this purpose. The target
      population for therapeutic exercise consists mainly of functionally independent
      persons with RA [3]. For these individuals, aerobic exercise seems superior to
      nonaerobic methods of exercise [4]. Likewise, dynamic exercise, requiring muscle
      work during joint motion, appears to be superior to static or isometric exercises
      [5].

PMID- 7734478
TI  - Exercise in the management of osteoarthritis of the knee and hip.
AB  - Osteoarthritis OA is a disorder that confines itself to affected joints; however,
      impairment, functional limitation, and disability related to OA can reach far
      beyond the perimeters of articular cartilage and subchondral bone. OA often is
      compared to other arthritides and defined by what it is not: OA is not a systemic
      disease; OA is not a disease of primary inflammation; OA is not life threatening.
      Too often OA also has been considered not interesting, not important, and not
      responsive to conservative treatment. However, reports documenting the personal
      and socioeconomic impact of OA are increasing recognition of its importance [1]
      and recent advances in understanding its pathogenesis are stimulating research
      [2]. OA is characterized by specific changes in articular cartilage and
      subchondral bone. Cartilage shows fibrillations, increased water content, and
      loss of integrity. Underlying bone is less compliant and may exhibit
      microfractures, sclerosis, and osteophytes at joint margins [3]. These changes
      result in increased friction, decreased shock absorption, and greater impact
      loading of the joint. The traditional view of OA is that the disease process
      starts with an unrepaired injury to articular cartilage. There is also evidence,
      however, that reduced compliance in bone and periarticular structures may
      initiate degenerative processes [4,5]. Although radiographic evidence of joint
      space narrowing and osteophytes may help confirm a diagnosis of OA, the clinical
      criteria for classification and reporting of hip and knee OA are described in
      terms of pain and limitation of motion [6,7] Table 1. Radiographic and laboratory
      data add little to the accuracy of these criteria [6]. Moreover, there is no
      clear association between radiographic findings and function or pain
      [8].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734479
TI  - Exercise considerations for postmenopausal women with osteoporosis.
AB  - Individuals with osteoporosis are at an increased risk of fracture due to a net
      loss of bone mass. The cellular mechanisms causing decreased bone mass are
      increased osteoclast-mediated bone resorption and/or decreased osteoblast
      mediated bone formation. Clinical studies have shown that bone loss can be
      prevented by estrogen replacement therapy and calcium supplementation. Weight
      bearing and strengthening exercise may also play a role in retarding bone loss in
      the postmenopausal woman, and it may even increase bone mass. The essential
      components of an exercise program include intensity, duration, frequency, and
      type of activity. Additional goals of a therapeutic exercise program are to
      improve flexibility and balance, and to prevent falls. Structure-function
      relationships in normal and osteoporotic bone and the effects of exercise on bone
      are reviewed. A rational approach for exercise strategies is discussed.

PMID- 7734480
TI  - Exercise in the spondyloarthropathies.

PMID- 7734481
TI  - Prescribing exercise for fibromyalgia patients.

PMID- 7734482
TI  - Physical conditioning in children with arthritis: Assessment and guidelines for
      exercise prescription.
AB  - OBJECTIVE: To review the literature in the area of physical fitness and
      conditioning programs for individuals with chronic illnesses, and increase the
      awareness of the need to include fitness testing and conditioning programs in the
      therapeutic management of children and adolescents with chronic arthritis.
      METHODS: This article provides a review of original research reports, information
      from principal texts, and review articles related to physical fitness testing and
      training in children. RESULTS: Several factors limit the exercise capacity of
      children with chronic arthritis, and studies report that these children have
      lower aerobic endurance and muscle performance than their peers. Preliminary
      studies suggest that fitness testing is safe for most children with arthritis,
      and physical conditioning programs, which appear to benefit adults with arthritis
      and children with other chronic illnesses, may also benefit children with
      arthritis. Easily administered, inexpensive field tests of fitness are available.
      Guidelines for prescribing physical conditioning programs are provided. The risks
      and benefits of increased exercise are discussed. CONCLUSIONS: Assessment of
      exercise capacity and muscle function and individualized prescription of physical
      conditioning programs are indicated for children with chronic arthritis, soon
      after diagnosis.

PMID- 7734483
TI  - What you can't afford to ignore about EMTALA.

PMID- 7734484
TI  - Workers' compensation introduction for physicians.
AB  - Workers' compensation is an important part of the employment system in this
      country, and its development was born out of necessity. In 1991, over 93 million
      employees were covered by workers' compensation statutes and laws for work
      related injuries and conditions. The costs over the past 20 years have increased
      at an overwhelming rate. These increases are being met by various cost
      containment strategies that are not omnipresent in all jurisdictions but instead,
      are being accepted and structured independently by each jurisdiction. Legislative
      changes are expected in the next few years to deter rising costs. The emerging
      patterns of cost containment are: limited initial provider choice, limited
      provider change, medical fee schedule, hospital payment regulation, utilization
      review, and bill review. The medical evaluation of impairment is a process that
      is not precise; however, impressive gains have arisen in this area through the
      use of the AMA Guides and DSM-IV.

PMID- 7734485
TI  - Public health in Virginia: immunization.

PMID- 7734486
TI  - Illness must be understood not in scientific but in human terms.

PMID- 7734487
TI  - Watch out for the "zebras".

PMID- 7734488
TI  - Plight of the homeless mental patient.

PMID- 7734489
TI  - A physician's road to the Olympics.

PMID- 7734490
TI  - Dual chamber permanent pacing in patients with hypertrophic cardiomyopathy. A
      report of three cases.

PMID- 7734491
TI  - [Serologic diagnosis of Lyme's disease. Is it still a pending problem?].

PMID- 7734492
TI  - [Analysis of Salmonella sp. serotypes isolated in Spain en 1988-1992].
AB  - BACKGROUND: Salmonella sp. is the main cause of bacterial diarrhoea in Spain.
      Serotyping, is the most widely applied epidemiological marker. The
      epidemiological distribution of Salmonella serotypes isolated in Spain is
      analyzed by statistical methods. METHODS: Salmonella isolates were serotyped
      according to standard methods and the results were analyzed by the Mantel
      Haenszel chi 2 test. RESULTS AND CONCLUSIONS: The number of isolates (20,595) was
      17% higher than those analyzed in the previous five year period (1983-1987),
      mainly due to an increase in the number of isolates from non human origin. The
      three most commonly isolated serotypes were Enteritidis, Typhimurium and Virchow.
      Serotype Enteritidis decreased along the analyzed period, probably because of the
      effectiveness of the socio-sanitary measures taken by the national and regional
      administrations such as legal issues (use of commercial mayonnaise in
      restaurants) and sanitary education.

PMID- 7734493
TI  - [Protective effect of dexamethasone and phenytoin in the treatment of
      experimental pneumococcal meningitis].
AB  - BACKGROUND: Pneumococcal meningitis has a high morbidity and mortality rate
      despite effective antibiotherapy, probably due to an exaggerated inflammatory
      response of the CNS. The use of dexamethasone and phenytoin reduced mortality in
      adults with pneumococcal meningitis. OBJECTIVE: We sought to determine the effect
      of dexamethasone, phenytoin or the association of both in several inflammatory
      parameters in experimental bacterial meningitis. METHODS: The study was performed
      using a modification of the rabbit model of Dacey and Sande. New Zealand white
      rabbits were intracisteranly inoculated simultaneously with heat-killed S.
      pneumoniae R6 dexamethasone, phenytoin or both. CSF leucocytes and concentration
      of proteins and lactate were determined over 6 hours, as well as the presence of
      brain edema. RESULTS: Treatment with dexamethasone alone or in association with
      phenytoin reduced all inflammatory parameters. The administration of phenytoin
      alone did not prevent an increase of CSF leucocytes or protein concentration, but
      did prevent the development of brain edema. A trend to wards a protective effect
      on the lactate concentration was observed. CONCLUSIONS: Our results gives support
      to the antiinflammatory effect of dexamethasone in experimental pneumococcal
      meningitis, and suggest that phenytoin may have also a protective effect on brain
      ischemia. This protective action and the prevention of brain edema could
      contribute, beyond its anticonvulsivant properties, to the great reduction in the
      mortality rate observed in some clinical studies in patients with pneumococcal
      meningitis.

PMID- 7734494
TI  - [Sensitivity of yeast isolates to amphotericin B and other antifungal inhibitors
      of beta-glucan synthesis].
AB  - BACKGROUND: Analysis of the in vitro sensitivity of clinical isolates of
      different yeast species to amphotericine B and two inhibitors of cell wall beta
      glucane synthesis: the lipopeptide cilofungin and the liposaccharide papulacandin
      B, as well as the possible interactions among these antifungal types. METHODS:
      The in vitro sensibility of C. albicans strains and other yeast species of
      clinical origin was studied, using the macrodilution method in RPMI broth as
      recommended by NCCLS. In six C. albicans and two T. glabrata strains the
      interaction between amphotericine B and one of the beta-glucan inhibitors was
      also assessed, by combining one antifungal agent in a two-fold dilution series
      with subinhibitory concentrations (1/4MIC) of the second antifungal. RESULTS AND
      CONCLUSIONS: Of all three antifungals, amphothericine B proved to be the more
      active one, with a MIC90 of 1.25 micrograms/ml for C. albicans. MIC90 of
      cilofungin and papulacandine B is 5 micrograms/ml for both antifungals. The
      spectrum of action for the different yeast species is broader for papulacandin B
      than for cilofungin. On the other hand, no synergism has been observed between
      the two glucane inhibitors and amphotericine B.

PMID- 7734495
TI  - [Agrobacterium radiobacter bacteremia. Study of 2 cases and review of the
      literature].
AB  - BACKGROUND: Agrobacteria are small gramnegative bacilli which produce tumors in
      different vegetal species and occasionally are human pathogens. METHODS: A
      retrospective review was carried out and the contribution of 2 cases of
      bacteremia by Agrobacterium radiobacter reported. RESULTS: Both patients
      developed uncomplicated bacteremia easily controlled by antimicrobian treatment
      without requiring removal of the intravascular device in one. CONCLUSIONS:
      Agrobacterium is a rare cause of bacteremic infection in immunosuppressed
      patients with intravenous catheters. Although the isolations are sensitive to
      different antibiotics some strains present resistance to cefalosporines,
      aminoglycosides and cloramphenicol. The mortality of these infections is slight.

PMID- 7734496
TI  - [Epidemic outbreak of shigellosis following water intake].
AB  - BACKGROUND: To describe the clinical, epidemiologic and microbiologic
      characteristics of an outbreak of shigellosis. METHODS: Twenty-six patients
      affected by shigellosis were studied. Upon identification of the outbreak, a
      questionnaire was carried out in relatives to determine the attack-rate. Studies
      of the isolated strains included biotype, antibiotype, and in 8 selected strains,
      plasmid and ribotyping profile. RESULTS: From September 23 to October 21 1991, 26
      patients (42% males, 54% under the age of 14 years), 23 of whom drunk water from
      two nearby fountains were attended for acute gastroenteritis and positive stool
      culture with isolation of Shigella sonnei strains with identical biochemical
      pattern and sensitivity. Only 2 required hospital admission and all recovered
      well. Forty-five percent of the 80 individuals who had drunk water from the
      fountains were affected. The attack-rate was higher in children (67%) than in
      adults (27%) (p < 0.001). The plasmid profile was identical in the strains
      studied. The only discriminative endonuclease used for the ribotyping was Sal I,
      which allowed the strains corresponding to the outbreak to be differentiated from
      those used as controls. CONCLUSIONS: An outbreak of shigellosis due to water
      ingestion is herein reported. The usefulness of plasmid profile as an
      epidemiologic marker of Shigella is confirmed. Only one of the four enzymes used
      for the ribotyping was discriminative. A greater susceptibility to infection was
      observed in children.

PMID- 7734497
TI  - [Community-acquired pneumonia].

PMID- 7734498
TI  - [Criteria for antibacterial susceptibility in vitro].

PMID- 7734499
TI  - [Optimal strategies for lot studies].

PMID- 7734500
TI  - [A woman with odynophagia, trismus, and bilateral empyema].

PMID- 7734501
TI  - [Vision disorders and ocular lesions in an AIDS patient].

PMID- 7734502
TI  - [Cerebral septic metastasis associated with hepatic abscess].

PMID- 7734503
TI  - [Clostridium perfringens septicemia in the absence of predisposing factors].

PMID- 7734504
TI  - [Xanthomonas maltophilia aortic endocarditis in an intravenous drug addict and
      review of the literature].

PMID- 7734505
TI  - [Salmonella virchow meningitis in an infant].

PMID- 7734506
TI  - [Plesiomonas shigelloides enteritis: clinical and epidemiologic aspects].

PMID- 7734507
TI  - [Varicella zoster pneumonia. Treatment with orally administered acyclovir].

PMID- 7734508
TI  - [Microbiological, macroscopic, and microscopic quality of sputum: current value
      of the study of their interrelationship].

PMID- 7734509
TI  - [Legionella dumoffii pneumonia].

PMID- 7734510
TI  - [Fusarium solani peritonitis: infrequent complication of peritoneal dialysis].

PMID- 7734511
TI  - [Cefepim].

PMID- 7734512
TI  - The Second National Biotechnology Summit.

PMID- 7734513
TI  - The importance of accurate terminology in the field of human gene transfer.

PMID- 7734514
TI  - Suppression of single and double nonsense mutations introduced into the
      diphtheria toxin A-chain gene: a potential binary system for toxin gene therapy.
AB  - We have previously shown that ablation of specific cells can be achieved through
      the transcriptionally regulated expression of the diphtheria toxin A-chain (DT-A)
      gene in both cell culture and transgenic mice. Such targeted toxin gene
      expression provides a novel approach to cancer and acquired immunodeficiency
      syndrome (AIDS) therapy. The use of mutants of DT-A with attenuated toxicity may
      allow targeting of cells for which only moderately selective gene regulatory
      elements are available. Alternatively, conditional mutants might be used to
      target cells in which conditions can be established for suppression of the
      mutation. We have investigated the effects of mutating selected serine codons to
      amber (TAG) nonsense codons in the DT-A coding sequence. In transient
      transfection of HeLa cells, DT-A activity was markedly reduced by the
      introduction of a single amber codon and was virtually eliminated by two amber
      mutations. Cotransfection of a serine inserting suppressor tRNA expression
      plasmid substantially restored DT-A expression from both single and double amber
      mutants. Expression of the same suppressor tRNA also suppressed a previously
      described amber mutation at the tyrosine codon 28 in DT-A. Thus, nonsense
      suppression can be used to control the expression of DT-A in mammalian cells,
      potentially allowing binary control over the targeting of tissues for selective
      ablation.

PMID- 7734515
TI  - Replication-deficient adenovirus induces expression of interleukin-8 by airway
      epithelial cells in vitro.
AB  - Preclinical studies with first-generation adenovirus (Ad) vectors administered in
      vivo to the respiratory tract have demonstrated a nonspecific host response
      consisting, in part, of parenchymal neutrophil accumulation followed by
      mononuclear cell and macrophage accumulation. We hypothesized that the mechanism
      for this host response might be the elaboration of interleukin-8 (IL-8) and
      monocyte chemoattractant protein-1 (MCP-1) from the airway epithelium following
      the exposure to Ad. To evaluate this hypothesis, we infected A549 cells (a human
      derived lung epithelial cell line) in vitro with an adenovirus type 5 (Ad5)-based
      vector expressing a nuclear targeted beta-galactosidase enzyme (Av1LacZ4). We
      found that cellular transduction was efficient, resulting in gene delivery to
      85.5% +/- 3.9% of the cell monolayer after 96 hr. Importantly, IL-8 mRNA
      transcript levels in Av1LacZ4-transduced cells were significantly higher than
      uninfected controls by 24 hr and remained elevated for 96 hr. IL-8 protein
      secretion from Av1LacZ4-transduced cells was increased for the same period. The
      Av1LacZ4-transduced A549 cells also showed a neutrophil chemoattractant activity
      higher than control cells, measurable at 24 hr, and persisting for 96 hr. The
      chemoattractant activity could be neutralized by a specific monoclonal antibody
      to IL-8. Whereas Av1LacZ4 transduction induced IL-8 gene expression, there was a
      lack of expression of MCP-1 by A549 cells. These observations demonstrate that
      the gene delivery to the airway epithelium using the Ad5-based expression vector
      results in IL-8 gene activation in these cells, which may contribute to the
      described inflammatory host response.

PMID- 7734516
TI  - Safety evaluation of Ad5CMV-p53 in vitro and in vivo.
AB  - In preparation for a clinical trial of the recombinant p53 adenovirus Ad5CMV-p53
      for the treatment of lung cancer, the potential adverse effects of Ad5CMV-p53
      were assessed in vitro and in vivo. No infectious replication of Ad5CMV-p53 was
      detectable in HeLa cells infected with extracts from HeLa cells previously
      infected with Ad5CMV-p53. No Ad5CMV-p53 DNA replication was detected by 32Pi
      labeling in lung cancer cells infected with Ad5CMV-p53 at multiplicities of
      infection (moi) up to 1,000 pfu/cell (total of 5 x 10(9) pfu viruses). The
      infectivity and cytotoxicity of Ad5CMV-p53 were examined in vitro in normal human
      bronchial epithelial (NHBE) cells. At a moi of 50 pfu/cell, Ad5CMV-p53 infection
      and expression were detectable in 80% of the treated cells. The exogenous p53
      protein was first detected by western blotting at 8 hr and peaked at 48 hr after
      infection. Growth of NHBE cells was not affected by Ad5CMV-p53 infection at a moi
      of 100 pfu/cell. The pathogenicity of Ad5CMV-p53 was assessed in BALB/c mice. The
      virus was given to four groups of mice by intratracheal injection at dosages from
      10(7) to 10(10) pfu; a fifth group received phosphate-buffered saline alone. None
      of the viral injections proved to be lethal. Mild to moderate peribronchiolar and
      perivascular infiltration by mononuclear cells and lymphocytes, with patches of
      pneumonitis, was the most acute toxic effect detected by histologic analysis in
      the two high-dose groups. Immunohistochemical analysis of the same paraffin
      embedded sections showed that infectivity and level of expression of p53 in lung
      tissue were dose-dependent. Our results demonstrate that Ad5CMV-p53 is a
      replication-defective virus that yields a relatively low degree of acute toxicity
      in mice; these data document a safety profile encouraging for clinical trials of
      Ad5CMV-p53 in the therapy of lung cancer.

PMID- 7734517
TI  - Correction of the growth defect in dwarf mice with nonautologous
      microencapsulated myoblasts--an alternate approach to somatic gene therapy.
AB  - Most of the currently approved human gene therapy protocols depend on genetic
      modification of autologous cells. We propose an alternate and potentially more
      cost-effective approach by implanting genetically modified "universal" cell lines
      to deliver desired gene products to nonautologous recipients. The recombinant
      allogeneic cells are protected from rejection after implantation by enclosure
      within immuno-protective alginate-poly-L-lysine-alginate microcapsules. The
      clinical efficacy of this strategy is now demonstrated by implanting
      microencapsulated allogeneic myoblasts engineered to secrete mouse growth hormone
      into the growth hormone-deficient Snell dwarf mice. The treated mutants attained
      increases in linear growth, body weights, peripheral organ weights, and tibial
      growth plate thickness significantly greater than those of the untreated
      controls. Secondary response to the exogenous growth hormone stimulation also
      resulted in increased fatty acid metabolism during the first month post
      implantation. The microcapsules retrieved after about 6 months of implantation
      appeared intact. The encapsulated myoblasts retained a viability of > 60% and
      continued to secrete mouse growth hormone. Thus, implantation of nonautologous
      recombinant cells corrected partially the pleiomorphic effects of a transcription
      factor mutation in the Snell dwarf mice and the encapsulated cells remained
      functional for at least 6 months. This simple method of delivery recombinant gene
      products in vivo is a benign procedure, obviates the need for patient-specific
      genetic modification, and is amenable to industrial-scale quality control. It
      should have wide applications in therapies requiring a systemic continuous supply
      of recombinant gene products.

PMID- 7734518
TI  - Human immunodeficiency virus type 2 (HIV-2): packaging signal and associated
      negative regulatory element.
AB  - Human immunodeficiency virus type 2 (HIV-2)-based retroviral vectors will have
      several desirable features as vehicles for gene therapy. These include target
      cell specificity, regulated expression, and attenuated cytopathicity. Such
      vectors require efficient packaging of RNA into retroviral particles which
      depends on a cis-acting sequence element called packaging signal or psi site. For
      most retroviruses, the principal part of this element is located between the
      major splice donor site and the gag initiator codon (AUG) in the leader sequence.
      The deletion of the corresponding region of HIV-2 did indeed cause a packaging
      defect; however, it did not abolish RNA encapsidation and viral infectivity.
      Additionally, deletions in this region resulted in an increase in intracellular
      viral RNA and extracellular p27 core antigen. However, only a fraction of the
      intracellular viral RNA was packaged into mature particles. These effects
      appeared to be sequence specific as deletion of the sequence elements upstream of
      the splice donor site did not result in increased viral RNA and proteins. A
      computer-assisted analysis of the leader sequence of viral RNA shows it to be
      rich in secondary structure, which was markedly altered in the deletion mutants.
      Thus, the leader sequence of HIV-2 between the splice donor site and the gag ATG
      has at least two regulatory functions: one positive, affecting encapsidation, and
      the other negative, regulating virus expression. Because there is only a limited
      sequence or structural homology between the corresponding region of HIV-1 and HIV
      2, they are likely to differ in their pathways regulating packaging and gene
      expression.

PMID- 7734519
TI  - Injection of colon carcinoma patients with autologous irradiated tumor cells and
      fibroblasts genetically modified to secrete interleukin-2 (IL-2): a phase I
      study.

PMID- 7734520
TI  - Manganese toxicity: free amino acids in the striatum and olfactory bulb of the
      mouse.
AB  - We studied the levels of twenty two free amino acids in the striatum and
      olfactory bulb of mice treated during nine weeks with daily intraperitoneal
      injections of manganese chloride at a concentration of 5.0 mg Mn+2/kg body
      weight. In the olfactory bulb the contents of alanine, alpha-amino-n-butyrate,
      arginine, asparagine, aspartate, citrulline, GABA, glutamate, glycine,
      isoleucine, leucine, methionine, phenylalanine, serine, threonine, tyrosine, and
      valine were diminished. No alterations were observed in the concentrations of
      free amino acids in the striatum of Mn-treated mice. The changes detected in the
      olfactory bulb merit a thorough evaluation in order to determine its importance
      on the pathophysiology of manganese poisoning.

PMID- 7734521
TI  - [Application of the high resolution chromosomic technic in patients in high risk
      of cytogenetic anomalies].
AB  - Since the beginning of cytogenetics, there has been a constant improvement of
      chromosomal culture and banding techniques. In 1976, Yunis described a high
      chromosomal resolution technique (HRC), that permits the detection of subtle
      chromosomal abnormalities. The present work, reports the results obtained when
      HRC was applied to the study of chromosomal abnormalities in patients with high
      risk of such. The study comprised 434 specimens of venous blood and 182 bone
      marrow aspirates. The samples were classified according to the presuntive
      diagnoses. The highest frequency of chromosomal abnormalities, was found in blood
      samples from patients with physical deformities with or without mental
      retardation (22.22%), followed by mental retardation autism and/or fragile X
      chromosome (13.66%), and in couples with reproductive disorders (5.8%). In bone
      marrow, the most frequent abnormalities corresponded to patients with chronic
      myeloid leukemia (78.43%), acute lymphocytic leukemia (62.10%), acute myeloide
      leukemia (61.9%), myelodisplastic syndromes (43.7%) and chronic lymphocytic
      leukemia (14.2%). The present results stress the need to apply the HRC technique
      when the probability of minute chromosomal abnormalities is high.

PMID- 7734522
TI  - [Molecular diagnosis of Duchenne/Becker muscular dystrophy in Venezuelan patients
      with the polymerase chain reaction].
AB  - Duchenne and Becker muscular dystrophy (DMD/BMD) are recessive X-linked
      neuromuscular diseases produced by allelic mutations in the human dystrophin gen.
      In the present study we determined the 14-deletion prone exons by multiplex PCR
      in 24 no related venezuelan patients with clinical diagnosis of DMD/BMD. We found
      37% of intragenic deletions of which 77% were located at the "hot spot" deletion
      region that includes exons 44 to 55. The present study show that deletion
      frequency observed in venezuelan patients resembles some Asian populations and is
      lower than that observed in Europe and North America. The explanation of the low
      frequency detected in our patients is beyond the present study, but it is likely
      that different mutations, ocurring at other regions of the gene is determining a
      molecular heterogeneity of the DMD/BMD disease in Venezuela.

PMID- 7734523
TI  - [Human ehrlichiosis. Review].
AB  - Human ehrlichiosis is a newly recognized tick-borne disease. Since 1935 Ehrlichia
      canis has been known as a cause of illness in dogs and other canine species, and
      for a few years it was related with human disease. In 1990, Ehrlichia chaffeensis
      was isolated from a man suspected of having ehrlichiosis. Partial sequencing of
      the rRNAS from the human isolate and E. canis, indicated that they are 98.7%
      related. More recently (May 1994) an "human granulocytic ehrlichiosis" have been
      reported in USA. PCR amplification and sequence of 16S rDNA, showed that the
      human isolate was virtually identical to those reported for E. phagocytophila y
      E. equi, organisms that cause ehrlichiosis in rumiant and in horses. Most
      patients shows fever, headache, malaise, nausea or vomiting, anorexia and in a
      minority of cases rash is present. Some of them have complications such as
      pulmonary infiltrates, gastrointestinal problems, renal dysfunction or failure,
      hepatoesplenomegaly, neurologic abnormalities, DIC and some times death.
      Leucopenia, thrombocytopenia and elevated liver enzyme values have been common
      findings. Tetracycline and cloramphenicol have been using in adults and children
      as especific theraphy.

PMID- 7734524
TI  - Quality assurance for picture archiving and communcication systems (PACS) and
      PACS technology applications in radiology.

PMID- 7734525
TI  - Quality control of cathode-ray tube monitors for medical imaging using a simple
      photometer.
AB  - As computer monitors are used more in medical imaging and the use of picture
      archiving and communication system workstations with multiple monitors is
      increasing, quality control protocols become necessary to track subtle variations
      in performance characteristics. Several tests based on previously published work
      were applied to 10 monitors of three different types over a period of 5 months.
      Each test is explained, and the results are shown. For example, without
      corrective adjustments, 2 monitors from the same workstation showed a small but
      steady decline in maximum luminance of 8.1% and 7.6% over the course of 11 weeks
      that was not perceptible. From this experience, we took the first step toward
      developing a practical and useful quality control protocol. The proposed protocol
      requires only a photometer and the ability to generate the Society of Motion
      Picture and Television Engineers (SMPTE) test pattern, and takes approximately 5
      minutes per monitor per week to gather data.

PMID- 7734526
TI  - Introduction to perceptual linearization of video display systems for medical
      image presentation.
AB  - The perceptual linearization of video display systems should play a significant
      role in medical image presentation. It maximizes the faithfulness of information
      transfer to the human observer; it provides a method for standardizing the
      appearance of images across different display devices; and it allows for
      calculation of the inherent contrast resolution of different display devices.
      This paper provides insight into the process of perceptual linearization by
      decomposing it into the digital driving level-to-monitor luminance relationship,
      the monitor luminance-to-human brightness perception relationship, and the
      construction of a linearization function derived from these two relationships. A
      discussion of previous work in these areas is given. We then compare and contrast
      the results of previous work with recent experiments in our laboratory and
      related work in vision and computer science. We conclude that (1) sufficiently
      good visual models exist for agreeing on a standard method of calculating the
      perceptual linearization function; (2) improvements in the resolution and
      luminance distribution of the digital-to-analog circuitry in display systems are
      required for medical imaging; and (3), methods for calculating a linearization
      remapping from a perceptual linearization function currently have significant
      error and should be replaced with methods that minimize perceptual error.

PMID- 7734527
TI  - A test pattern for quality control of laser scanner and charge-coupled device
      film digitizers.
AB  - Although clinical images provide the ultimate test of diagnostic performance for
      a film digitizer, such images are not generally suitable for daily quality
      control (QC) purposes. However, a well-designed test pattern will provide a
      rapid, comprehensive, objective and reproducible assessment of image quality.
      This pattern should evaluate various parameters of image quality, including high
      contrast resolution, low contrast discrimination, linearity of gray scale,
      geometric distortion, and noise. Furthermore, the pattern should detect light
      leak and film slippage, two problems commonly associated with film digitizers.
      The test pattern described in this manuscript was designed to provide
      quantitative measures of performance for a film digitizer. As part of a regular
      QC routine for a laser scanner or charge-coupled device digitizer, this pattern
      provides a simple method to identify and quantify changes in digital image
      quality.

PMID- 7734528
TI  - Coronary artery mapping: a method for three-dimensional reconstruction of
      epicardial anatomy.
AB  - Evaluation of coronary anatomy with conventional coronary angiography requires
      visual integration of multiple images from different viewing orientations to
      generate a mental interpretation of three-dimensional (3D) structure. The
      epicardial surface is, in many ways, analogous to the earth's surface topography
      and may be effectively depicted using cartographic methods. To show coronary
      anatomy visualized as topographic maps, we used cartographic projection methods
      to analyze the coronary vessels of a canine heart after immediate postmortem
      injection with a radio-opaque gelatinous solution. A volumetric image data set
      was obtained with x-ray spiral computed tomography. The principal axis of the
      image volume was calculated and the image volume reformatted to a reference
      coordinate system defined by the principal axis as the ordinate. A cylindrical
      projection map of the epicardial surface was created using a maximum-intensity
      projection volume-rendering technique. After converting the Cartesian reference
      coordinate system to a polar coordinate system, additional mapping projections
      from user-defined orientations were generated. The results show that
      interpretative difficulties of coronary angiography may be diminished by
      generating 3D maps of coronary anatomy using volumetric datasets acquired
      noninvasively and displayed with cartographic methods.

PMID- 7734529
TI  - Initial experience with asynchronous transfer mode for use in a medical imaging
      network.
AB  - Picture archiving and communication Systems (PACS) for medical imaging have
      always suffered from band-width limitations, throughput, and proprietary
      protocols. Commercially available local area networks have been hard pressed to
      meet the requirements of image transfer in a time consistent with patient-care
      needs. Recent technologic advances provide potential solutions to these
      constraints. Asynchronous transfer mode (ATM) provides the aggregate bandwidth
      and throughput that may be sufficient to satisfy the medical imaging community.
      Networks using prototype ATM technology have been available and commercial
      hardware is now becoming available. This report presents initial performance
      results of an ATM network and its suitability for use in a digital imaging
      network. Throughput of 10 Mbytes/sec was attained with Transmission Control
      Protocol/Internet Protocol using commercially available hardware.

PMID- 7734530
TI  - 1st International Digital Image Symposium. Digital imaging: clinical evaluation
      and future potential. June 4-5, 1994, Osaka, Japan. Proceedings.

PMID- 7734531
TI  - Digital chest radiography at the University of Chicago: present status and future
      plans.
AB  - Storage-phosphor computed radiography and film digitization systems have been in
      routine clinical use at the University of Chicago for several years. During this
      time we have implemented numerous modifications including techniques for scatter
      reduction, image processing enhancements and display systems to improve the image
      quality and utility of these devices. We have also evaluated the image quality
      and functionality of digital systems relative to conventional screen-film
      radiography. In this paper, we review our experience and summarize our
      impressions. In addition, we summarize our plans for a rapid transition into
      picture archiving and communication systems, with hardcopy interpretation being
      phased out for most modalities over the next 2 to 5 years.

PMID- 7734532
TI  - Digital chest radiography: clinical aspects.
AB  - Technical development puts the completely digital radiology department within
      reach. Presently available systems have slightly inferior spatial resolution than
      film/screen systems. This is well compensated for by image processing. In the
      future, the digital radiology department working environment will be different.
      Systems should be designed that conform as much as possible to radiologists'
      present way of working to facilitate transition to the new system and avoid
      unnecessary stress.

PMID- 7734533
TI  - Potential usefulness of digital imaging in clinical diagnostic radiology:
      computer-aided diagnosis.

PMID- 7734534
TI  - AKAMAI Project: teleradiology in the Pacific.

PMID- 7734535
TI  - Clinical application of single dual-energy subtraction technique with digital
      storage-phosphor radiography.
AB  - We used a single-exposure dual-energy subtraction technique with a storage
      phosphor computed radiography (CR) system to evaluate various pulmonary diseases.
      Clinical applications of this method have been studies at our institution. In our
      experience, the dual-energy subtraction technique provided better visualization
      of pulmonary nodules, tracheobronchial abnormalities, pulmonary vascular
      diseases, calcification in a nodule, and rib lesions than conventional CR images
      did. Single-exposure dual-energy subtraction images were obtained with a sandwich
      technique using two storage-phosphor imaging plates with a 1-mm-thick copper
      filter interleaved between the two. The front plate obtains a lower kilovoltage
      image, whereas the back plate obtains a higher kilovoltage image. We can
      visualize soft tissue and bone images as well as unsubtracted digital images by
      the subtraction process.

PMID- 7734536
TI  - Diagnostic usefulness of chest computed radiography--film versus cathode-ray tube
      images.
AB  - Seventy-one plain chest images obtained by computed radiography (CR) with an
      imaging plate were interpreted on film and two kinds of cathode-ray tube (CRT)
      monitors installed separately at two facilities (1,024 x 1,536 pixels, 8 bits,
      and 1,024 x 1,280 pixels, 10 bits) by 20 radiologists and four chest internists.
      The clinical categories of these 71 cases included pulmonary nodules and
      interstitial abnormalities. Image reading sessions were held over a total of 4
      days, ie, 2 days and then another 2 days, 3 weeks later. Twenty-four observers
      formed four groups with six members each. Two groups read either films or CRT
      images at one of the two facilities. In the second experiment, 26 of 71 images
      were compressed at 10:1, 19 of 71 were compressed at 20:1, and 26 were not
      compressed. Analyses of the areas under the receiver-operating characteristic
      curves showed no significant differences in detection of pulmonary abnormalities
      between film and CRT. In detecting interstitial pulmonary abnormalities, film was
      more sensitive than CRT monitor. There were no significant differences in
      observers' performances between the two different kinds of CRT workstation.
      Subjective evaluation of image quality showed that images irreversibly compressed
      to the ratios of 10:1 and 20:1 were inferior to original images. Although further
      considerations are needed with regard to spatial resolution requirements, image
      processing, and image compression, the utilization of CR CRT image as a
      substitute for CR film image will be possible.

PMID- 7734537
TI  - Interpretation of subtle interstitial chest abnormalities: conventional
      radiography versus high-resolution storage-phosphor radiography--a preliminary
      study.
AB  - To evaluate the reliability of digital chest radiography in diagnosing subtle
      interstitial lung abnormalities, we performed several clinical studies including
      a comparison of conventional screen-film radiography and storage-phosphor
      radiography (2 K x 2 K pixels, 10 bit), and a comparison of conventional screen
      film radiography and film-digitized radiography (2 K x 2 K pixels, 10 bit). From
      these previous studies, a spatial resolution of 0.2-mm pixel size was considered
      inadequate to diagnose subtle interstitial lung diseases. Under these
      circumstances, the newly developed Fuji Computed Radiography system (FCR 9000;
      Fuji Photo Film, Tokyo, Japan) has recently become available. This system
      provides 0.1-mm pixel size (4 K x 5 K pixels, 10-bit depth) and life-size hard
      copies (14 x 17 inches). To evaluate the reliability of new high-resolution
      storage-phosphor radiography (FCR 9000) in diagnosing simulated subtle
      interstitial abnormalities (including simulated lines, micronodules, and
      groundglass opacities), the differences among radiologists in interpreting
      conventional screen-film radiographs and life-size high-resolution storage
      phosphor radiographs were studied. Observation was made by eight experienced
      chest radiologists and receiver-operating characteristic (ROC) analysis was
      performed. There was no significant difference in detecting in subtle simulated
      interstitial abnormalities between conventional film-screen radiography and high
      resolution storage-phosphor radiography. For all three types of abnormalities,
      there was no significant difference between conventional and storage-phosphor
      radiography. In conclusion, the high-resolution storage-phosphor chest
      radiography (0.1-mm pixel size, 10-bit depth) may be substituted for conventional
      chest radiography in the detection of subtle interstitial abnormalities.

PMID- 7734538
TI  - Digital radiography of the musculoskeletal system: the optimal image.
AB  - Digital radiography (DR) is replacing screen-film (SF) radiography for
      musculoskeletal examinations in our institution. After an iterative process of
      image quality improvement, our DR images are now preferred to SF images, and we
      have detailed our current optimized settings for the Fuji 9000 (Fuji Medical
      Systems, Tokyo, Japan). DR offers the advantages of improved contrast resolution,
      adjustable image contrast, the ability to reprocess the image, and the ease of
      transferring the image to an image management and communication system (IMAC).

PMID- 7734539
TI  - Digital skeletal radiography.

PMID- 7734540
TI  - A comparison of hard and soft copies processed with linear conversion and
      nonlinear conversion of skeletal fractures--a preliminary study.
AB  - To compare hard copies and soft copies processed with linear and nonlinear
      conversion of skeletal fractures, we performed a receiver-operating
      characteristics study of 25 digital radiographs. There was no statistical
      difference between hard copies with linear and nonlinear conversion. However, it
      may be difficult to detect small fractures on images processed by nonlinear
      conversion. No significant difference was seen between CRT diagnosis and that on
      a hard copy processed with linear conversion and frequency enhancement.

PMID- 7734541
TI  - Clinical application of computed radiography in orthopedic surgery.
AB  - Since 1988, Fuji Computed Radiography (FCR) system (Fuji Medical Systems, Tokyo,
      Japan) has been used at Osaka Prefectural Hospital (Osaka, Japan) for all kinds
      of images. In this paper, we discuss the advantages and disadvantages of computed
      radiography (CR) images from the standpoint of an orthopedic surgeon. Contours,
      which can not be seen on conventional radiographs, are clearly visualized on the
      CR image. Adequate information for diagnosis can be obtained with a great
      reduction in x-ray exposure during the screening of scoliosis or congenital
      dislocation of hip joint. However, because the scale is reduced by one half in
      antero-posterior views of the bilateral hip joint, CR images are unsuitable for
      postoperative measurement of total hip arthroplasty (THA). Furthermore, caution
      is required because the clear zone after THA is emphasized on edge-enhanced CR
      image.

PMID- 7734542
TI  - Clinical aspects of direct digital mammography.
AB  - Since 1990, computed radiography (CR) has been used routinely in our symptomatic
      mammography service, imaging approximately 2,000 patients per year. Careful
      selection of the appropriate image processing parameters results in high-quality
      images of diagnostic value equivalent to conventional film-screen mammograms.
      Problems encountered included dust artifacts, black films, and white films, but
      these constituted only a very small proportion of images obtained and the
      remedies are discussed. Hard-copy reporting is used and improved image
      presentation is considered. New processing algorithms and the development of soft
      copy reporting at dedicated workstations are expected in the near future.

PMID- 7734543
TI  - Evaluation of digital mammography in diagnosis of breast cancer.
AB  - Mammography has been digitized in all cases at our hospital. Digital mammography
      (MMG) of our hospital and its diagnostic accuracy were described in this report.
      Fuji Computed Radiography (FCR; Fuji Medical Systems, Tokyo, Japan) imaging plate
      was used and imaging data were processed with FCR 7000 or FCR 9000. Each image
      was output to a single hard copy. Sampling pitches for reading and output were
      0.1 mm. The rate of breast cancer diagnosis by digital MMG was 67%, 95%, 94%, and
      100% for unpalpable tumor, tumor less than phi 2 cm, tumor of phi 2 to 5 cm, and
      tumor greater than phi 5 cm, respectively, being 94% overall. Digital MMG enables
      us to establish goal-oriented image-processing conditions. The use of digital
      MMG, which provides an excellent diagnostic rate similar to that of screen-film
      MMG, is expected to became wide-spread in the near future.

PMID- 7734544
TI  - Dual-energy subtraction mammography.
AB  - Dual-energy subtraction mammography was performed for breast examinations. To
      obtain a dual-energy subtraction image with a digital radiography unit, high- and
      low-energy images were obtained at an appropriate time interval under different x
      ray exposure conditions. In about 50% of the patients with breast cancer included
      in this study, we obtained better diagnostic accuracy with dual-energy
      subtraction images than with conventional mammography. In some cases of breast
      cancer, it is possible to diagnose intraductal spread of this lesion on the
      subtracted images. Furthermore, abnormal lesions commonly observed on mammography
      in cases of fibrocystic disease tended to be erased on subtracted images. Thus,
      dual-energy subtraction mammography provided useful information for diagnosing
      breast diseases. However, there were several cases in which the subtracted images
      lacked sufficient image quality, and several technical problems with subtraction
      are thought to remain.

PMID- 7734545
TI  - Clinical use of digital mammography: the present and the prospects.
AB  - Digital mammography is likely to replace the current routine breast imaging
      technology in the future because it offers advantages that should lead to both
      improved image quality and interpretation. Hopefully, this will result in earlier
      detection in breast screening programs and decreased mortality from the most
      frequently diagnosed of all cancers after skin cancer, which is far less deadly.
      At present, digital mammography has a limited clinical role; in the United
      States, it has been used for several years to localize lesions for tissue
      sampling using small field of view digital detectors. Once whole breast digital
      detectors are available, it seems clear that applying computer techniques to
      enhance and analyze the collected digital data will become routine. Results
      reported over the last decade indicate that computer-aided diagnosis can improve
      radiologists' observational performance, and it is likely that computer
      techniques to routinely enhance the decision-making ability of the average to
      below-average radiologist to the level of an expert will be developed. There are
      obstacles to these advances, but the combination of realizable technological
      solutions and the importance of the breast cancer problem clinically should
      provide sufficient where-withal and impetus to make digital mammography a
      clinical reality.

PMID- 7734546
TI  - Digital radiography: comparison of different methods for imaging of the thorax
      and the gastrointestinal tracts.
AB  - In evaluating the image quality of the chest, four different analog and digital
      methods were compared. For peripheral lung field, the advanced multiple beam
      equalization radiography (AMBER) system was given the best score, followed in
      order by the storage-phosphor, conventional, and asymmetric film/screen systems.
      For the mediastinal field, the highest image quality was given to the AMBER
      system, followed by storage phosphor and asymmetric film/screen system. The best
      overall image quality, especially with regard to demonstration of pathologic
      alteration, was given to the AMBER system, followed by the storage-phosphor,
      conventional, and asymmetric film/screen radiography systems. In conclusion,
      AMBER demonstrated the highest image quality. The storage-phosphor system
      provided better results in the peripheral and mediastinal fields in comparison
      with conventional film/screen systems. Other digital systems including selenium
      chest radiography system and image intensifier digital radiography were also
      discussed.

PMID- 7734547
TI  - Gastrointestinal examinations with a 2,048- x 2,048-pixel image intensifier
      television digital radiography system.
AB  - The clinical usefulness of a 2,048- x 2,048-pixel matrix image intensifier
      television digital radiography system was evaluated. Screen-film and digital
      images (with and without postprocessing) of the upper and lower gastrointestinal
      (GI) tract were used for clinical evaluation. For the upper GI tract, digital
      images processed with unsharp mask techniques were comparable in quality to
      screen-film images before and after upgrading the system. For the lower GI tract,
      screen-film images were better than digital images, except for those processed
      with a 2,048- x 2,048-line monitor was comparable to a screen-film system.

PMID- 7734548
TI  - Clinical usefulness of digital radiography in the gastrointestinal tract:
      efficacy of magnification method.
AB  - We assessed the performance capabilities of image intensifier digital radiography
      (II DR) in the detection of minute lesions in patients with early stomach cancer.
      The DR system was a prototype II DR system developed by Toshiba Corp (Tokyo,
      Japan). This system was able to acquire images with a 1,024- x 1,024-pixel matrix
      and 12 bits. Radiography was performed using a 0.3-mm tube focus. For the
      detectability of early stomach cancer, DR was judged to be superior to
      conventional screen-film system (CFSS) (DR superior, 55.7%; CFSS superior,
      22.6%). In depicting the characteristics of the surface of the lesion, DR was
      also judged to be superior to CFSS (DR superior, 56.6%; CFSS superior, 17.0%).
      The II DR system used in this study was able to achieve almost the same spatial
      resolution as conventional radiography using the magnification method. It was
      also able to visualize subtle findings of early gastric cancer more clearly by
      the use of postprocessing. In addition, II DR has the advantages of reducing the
      patient exposure dose and permitting the acquisition of real-time images.

PMID- 7734549
TI  - Indications for digital fluorography and storage-phosphor plates in pediatrics:
      certainties and questionable points.
AB  - We have used two digital imaging systems: digital fluorography and the phosphor
      plates system. The respective indications for each technique in pediatric
      practice are presented hereafter. Digital fluorography is highly recommended by
      dynamic examinations, and phosphor plates are highly recommended for conventional
      studies, if the spatial resolution is mandatory. Either digital fluorography or
      phosphor plates can be used for contrast studies. In pediatric radiology, if the
      spatial resolution is not mandatory, digital fluorography is suggested to reduce
      the radiation dose, and if using a small fields of view is possible, digital
      fluorography may be carefully discussed. Digital radiography is supported neither
      to be better than classical radiology nor to compensate for technician's
      mistakes. It is aimed to improve the department's functioning and, above all, to
      accommodate future innovations. Images can be transferred or archived through
      networks. This is a main prospect in the coming years.

PMID- 7734550
TI  - Computed radiography in pediatrics.
AB  - Computed radiography (CR) has various advantages such as dynamic range.
      Diagnostic accuracy with CR using reduced radiation dose is considered comparable
      with that of conventional film-screen radiography in diagnosing apparent chest
      abnormalities. In addition to reducing the radiation dose, delineation of the
      various structures in infants can be obtained with CR using postprocessing. Even
      in cases involving inadequate exposure, appropriate information can be obtained
      by postprocessing. For these reasons, the cumulative dose of radiation exposure
      will be reduced. Thus, reduction of the radiation dose is the greatest advantage
      of using CR in pediatrics.

PMID- 7734551
TI  - A modular artificial neural net for controlling a six-legged walking system.
AB  - A system that controls the leg movement of an animal or a robot walking over
      irregular ground has to ensure stable support for the body and at the same time
      propel it forward. To do so, it has to react adaptively to unpredictable features
      of the environment. As part of our study of the underlying mechanisms, we present
      here a model for the control of the leg movement of a 6-legged walking system.
      The model is based on biological data obtained from the stick insect. It
      represents a combined treatment of realistic kinematics and biologically
      motivated, adaptive gait generation. The model extends a previous algorithmic
      model by substituting simple networks of artificial neurons for the algorithms
      previously used to control leg state and interleg coordination. Each system
      controlling an individual leg consists of three subnets. A hierarchically
      superior net contains two sensory and two 'premotor' units; it rhythmically
      suppresses the output of one or the other of the two subordinate nets. These are
      continuously active. They might be called the 'swing module' and the 'stance
      module' because they are responsible for controlling the swing (return stroke)
      and the stance (power stroke) movements, respectively. The swing module consists
      of three motor units and seven sensory units. It can produce appropriate return
      stroke movements for a broad range of initial and final positions, can cope with
      mechanical disturbances of the leg movement, and is able to react to an obstacle
      which hinders the normal performance of the swing movement. The complete model is
      able to walk at different speeds over irregular surfaces. The control system
      rapidly reestablishes a stable gait when the movement of the legs is disturbed.

PMID- 7734552
TI  - Investigating the effects of opioid drugs on electrocortical activity using
      wavelet transform.
AB  - Fetal electrocortical activity (ECoG) is characterized by two distinct patterns:
      HVSA (high voltage, slow activity) and LVFA (low voltage, fast activity). Using
      the wavelet transform (WT), we recently reported that the frequency
      characteristics of these two ECoG patterns undergo significant maturational
      changes prior to birth (Akay et al. 1994a). We now report that fetal ECoG can
      also be significantly affected by pharmacological agents. In this paper, we
      compared the effects of two opioid drugs (morphine and [D-Pen2, D-Pen5]
      enkephalin, DPDPE) on fetal ECoG, using the chronically instrumented fetal lamb
      model. Morphine was infused intravenously (i.v.) at 2.5 mg/h, while DPDPE was
      infused into the lateral cerebroventricle (i.c.v.) at 30 micrograms/h. The ECoG
      was analyzed using WT. We performed multi-resolution decomposition for four sets
      of parameters D2j where -1 < j < -4. The four series WTs represent the detail
      signal bandwidths: (1) 16-32 Hz, (2) 8-16 Hz, (3) 4-8 Hz, (4) 2-4 Hz. The data
      were subjected to statistical analysis using the Kolmogorov-Smirnov (KS) test.
      Both morphine and DPDPE resulted in a significant increase in power in the first
      wavelet band, while power was reduced in the second, third and fourth wavelet
      bands. In addition, both drugs resulted in a disruption of the normal cyclic
      pattern between the two ECoG patterns. There was a difference in the time course
      of action between morphine and DPDPE. This is the first occasion in which
      continuous ECoG has been subjected to rigorous statistical analysis. The results
      suggest that the WT-KS method is most suitable for quantitating changes in the
      ECoG induced by pharmacological agents.

PMID- 7734553
TI  - Modulated excitability: a new way to obtain bursting neurons.
AB  - Classical burster models are based on a fast system that either oscillates or is
      quiescent, depending on temporarily fixed values of slow variables. In a study of
      the lobster heart ganglion, we found a new type of burster for which the fast
      system is globally stable for all relevant fixed values of the slow variables. We
      describe how this burster works and speculate on its biological significance.

PMID- 7734554
TI  - Changes in peritoneal transport during the first month of peritoneal dialysis.
AB  - OBJECTIVE: To determine if peritoneal transport characteristics change during the
      initial month of peritoneal dialysis. DESIGN: Retrospective review of peritoneal
      equilibration test (PET) results in patients who received their first PET during
      the first two weeks of peritoneal dialysis (early PET group) versus patients who
      received their first PET between four and 28 weeks after the initiation of
      dialysis (late PET group). The initial PET values were compared to subsequent PET
      results obtained approximately seven months after the initial PET. SETTING:
      Peritoneal dialysis unit of a tertiary medical center. OUTCOME MEASURES: PET
      results and calculated mass transfer area coefficient (MTAC) values. PATIENTS:
      Thirty-four peritoneal dialysis patients in the early PET group and 17 peritoneal
      dialysis patients in the late PET group. RESULTS: In the early PET group, there
      was a statistically significant increase from the initial to follow-up values for
      both dialysate-to-plasma (D/P) creatinine and MTAC creatinine (p < 0.01) as well
      as a significant decrease for four-hour dialysate to initial dialysate ratios
      (D/Do) glucose (p = 0.08) and MTAC glucose (p < 0.05). In the late PET group,
      there was no significant change in any of these parameters with time. However, in
      the late PET group, there was a significant decrease in D/P urea values with time
      (p < 0.01), but not with MTAC urea. In addition, there were no differences over
      time in either group for serum albumin or hematocrit values. CONCLUSION: During
      the first two weeks of peritoneal dialysis, there tends to be a change in
      peritoneal transport characteristics in some patients. PET data obtained during
      this time period should be interpreted as preliminary.

PMID- 7734555
TI  - Comparison of straight and curled Tenckhoff peritoneal dialysis catheters
      implanted by percutaneous technique: a prospective randomized study.
AB  - OBJECTIVE: To examine the impact of peritoneal dialysis catheter configuration,
      curled or straight catheter, on catheter survival and mechanical and infectious
      complications. DESIGN: Prospective randomized trial. SETTING: Department of
      Nephrology of a single university hospital. PATIENTS: Seventy-two consecutive
      patients initiating peritoneal dialysis were randomized to receive either a
      single cuff straight catheter or a single cuff curled catheter, implanted by
      percutaneous technique. RESULTS: Significantly higher (p < 0.01) survival rate of
      the curled as compared to the straight catheter. The difference in catheter
      survival was due to a significantly higher (p < 0.01) incidence of drainage
      failure associated with catheter tip migration of the straight catheter than of
      the curled catheter. No difference in infectious complication between the two
      types of catheters was seen. Catheter survival at 12 months was 77% for the
      curled catheter and 36% for the straight catheter. CONCLUSION: This study
      demonstrates superiority of the curled Tenckhoff peritoneal dialysis catheter
      survival as compared to the straight catheter. This difference in catheter
      survival is due to the higher displacement rate of the straight catheter.

PMID- 7734556
TI  - Predicted and measured daily creatinine production in CAPD: identifying
      noncompliance.
AB  - OBJECTIVE: To evaluate the ratio of measured creatinine (Cr) production to
      predicted creatinine production as an index of noncompliance in patients on
      continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A cross-sectional
      analysis. PATIENTS: One hundred and twenty-one patients on CAPD. MEASUREMENTS: We
      have calculated Cr production from measured Cr outputs in 24-hour collections of
      urine and dialysate. Predicted Cr productions were calculated from standard
      tables. Weekly KT/V urea and weekly Cr clearances were determined from the same
      24-hour urine and dialysate collections. Lean body mass (LBM) was calculated from
      the Cr production. Serum albumin concentration was measured. RESULTS: The ratio
      of measured/predicted Cr production correlated positively and significantly with
      weekly KT/V urea, the protein equivalent of nitrogen appearance (PNA), weekly Cr
      clearance, and LBM. There was a decline in serum albumin concentration at ratios
      greater than 1.24, supporting the opinions of previous authors who have suggested
      that ratios greater than 1.24 are highly suggestive of noncompliance with the
      dialysis prescription. Defining noncompliance as a ratio greater than 1.24
      implied that at least 5% of the female and 17% of the male patients were
      noncompliant. CONCLUSIONS: Declining serum albumin concentrations at higher
      ratios of measured/predicted Cr production support the opinion that this is an
      index of noncompliance. However, not all noncompliant patients necessarily have a
      ratio greater than 1.24. Weekly KT/V urea, weekly Ccr and LBM are all
      artifactually increased by "washout effects" if all exchanges are done only or
      mainly on the collection day.

PMID- 7734557
TI  - Development of toxic degradation products during heat sterilization of glucose
      containing fluids for peritoneal dialysis: influence of time and temperature.
AB  - OBJECTIVE: Fluids for peritoneal dialysis (PD) cause cytotoxic reactions in many
      different in vitro systems. The low pH, the high osmolality of the fluids, and
      the glucose degradation products formed during heat sterilization have been
      considered responsible. In the present study, we investigate the influence of
      temperature and time during heat sterilization of PD fluids and glucose solutions
      on glucose degradation and cytotoxicity of the solutions. DESIGN: Ampoules
      containing PD-fluid or glucose solution were heated in an oil bath to
      predetermined F0 values (combinations of time and temperature giving equal
      energy/bacterial lethality). Cytotoxicity of the solutions was measured as growth
      inhibition of cultured L-929 fibroblasts. Glucose degradation was measured as UV
      absorbance at 228 and 284 nm. RESULTS: The same general pattern was seen in both
      PD fluid and glucose solution. Cytotoxicity decreased from 90% to 15% when the
      sterilization temperature was increased from 115 degrees to 140 degrees C and
      concomitantly the length of time shortened in order to maintain equal bacterial
      lethality. Under the same conditions, degradation products, measured as UV
      absorbance at 284 nm, decreased from 0.2 to 0.02. CONCLUSION: To minimize the
      development of cytotoxic breakdown products, high temperatures over short periods
      of time should be used to heat-sterilize PD fluids. Even as small an increase as
      5 degrees C at around 120 degrees C will improve the quality of the solutions.

PMID- 7734558
TI  - Successful self-care home dialysis in the elderly: a single center's experience.
AB  - OBJECTIVE: This study was designed to prospectively review our experience with
      self-care home dialysis in the 60-years-and-older age group since the
      commencement of continuous ambulatory peritoneal dialysis (CAPD) in our center in
      1989. DESIGN: Data on mortality, morbidity, dialysis technique and complications,
      quality of life, and rehabilitation were collected prospectively. SETTING: A
      regional dialysis unit providing full renal replacement services for a population
      of 292,000. PATIENTS: Twenty-five patients (16 male) with an average age of 64.4
      years (range: 58.25 - 76.5 years) at commencement of dialysis. RESULTS: All
      patients were on self-care home dialysis. Patient survival rates were comparable
      with the national average at 12 months (90% vs 89%) and two years (84% vs 80%).
      Dialysis therapy was well tolerated and technique survival rates were comparable
      for both hemodialysis and CAPD. There was a very low peritonitis rate of 1
      episode per 28.5 patient-months. CONCLUSIONS: Self-care home dialysis is a viable
      therapeutic option with a high degree of technique success and a good quality of
      life in the older population.

PMID- 7734559
TI  - Chronic peritoneal dialysis: seven-year experience in a large Hispanic program.
AB  - OBJECTIVE: To analyze the clinical results of our patient population on
      continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling
      peritoneal dialysis (CCPD) in relation to treatment modality systems, compliance,
      rehabilitation characteristics, complications, and survivals. DESIGN: The medical
      records of all patients trained on CAPD or CCPD between 1985 and 1992 were
      reviewed for the above-mentioned outcome objectives. SETTING: Outpatient CAPD
      facility affiliated to a tertiary care community hospital. PATIENTS: The total of
      305 patients trained during the study period were studied. MAIN OUTCOME MEASURES:
      The patients were studied for age, sex, primary renal disease, peritoneal
      dialysis modality, need of assistance from a partner during the dialysis
      procedure, causes of transfer and hospitalization, peritonitis, rehabilitation,
      patient compliance, and outcome including mortality. RESULTS:  PATIENT
      POPULATION: 179 (58.7%) males and 126 (41.3%) females, aged 1-80 years (mean 47.2
      +/- 15.09) with a total observation time of 15,753 patient-months. The most
      common diagnosis of the renal disease was diabetic nephropathy (41%). Peritonitis
      was the main cause of hospitalizations (36.7%) and of transfers (69.5%). Patient
      survival at one, two, and three years was 87.9%, 76.6%, and 67.0%, respectively.
      Likewise, technique survival was 65.5%, 45.5%, and 30.6%. Peritonitis rate for
      CAPD has improved from 1.9 episodes per patient-year to 1.2 episodes per patient
      year and an overall rate of 1.5 episodes per patient-year. CONCLUSIONS: The
      experience in a large Hispanic program shows a good patient survival rate.
      Although there is a trend to a lower peritonitis rate, this continues to be the
      main cause of transfer, hospitalization, and one of the main causes of death.

PMID- 7734560
TI  - Does impaired transcellular water transport contribute to net ultrafiltration
      failure during CAPD?
AB  - OBJECTIVES: To assess the contribution of transcellular water transport in net
      ultrafiltration failure during continuous ambulatory peritoneal dialysis (CAPD).
      DESIGN: Retrospective. SETTING: Renal Unit, Academic Medical Center, Amsterdam.
      PATIENTS: One group of 6 patients with clinical severe ultrafiltration loss and a
      group of 10 stable CAPD patients without ultrafiltration problems. INTERVENTION:
      In all patients, two peritoneal permeability tests were done within one week,
      using glucose 1.36% dialysate on one day and glucose 3.86% on the other day.
      Dextran 70 was used as a volume marker. RESULTS: The difference in net
      ultrafiltration between 3.86% glucose and 1.36% glucose dialysate was 569 +/- 51
      mL (control) and 153 +/- 103 mL (poor ultrafiltration group; p < 0.005). The
      dialysate/plasma (D/P) concentration ratios increased in both groups with glucose
      1.36%. When using 3.86% glucose, the D/P ratio decreased in the control group
      with a median minimum value one hour after completion of inflow. It is possible
      that sieving of sodium was due to transcellular water transport by crystalloid
      osmosis during the hypertonic dwell, as a dissociation between the transport of
      water and sodium is unlikely to occur in transport through the much larger
      intercellular pores. The D/P sodium ratio after one hour was related to the mass
      transfer area coefficient (MTC) of creatinine and the percentage of glucose
      absorption in the control group. No decrease in D/P ratio was found in the poor
      ultrafiltration group. This suggests impairment of transcellular water transport.
      No significant differences were present between both groups with regard to MTC
      creatinine (10.2 and 14.0 mL/min), glucose absorption (71% and 71%), effective
      lymphatic absorption rate (1.34 and 1.01 mL/min), and residual volume (248 and
      178 mL). Only 1 patient in the ultrafiltration loss group continued with CAPD.
      The others had to be transferred to hemodialysis; 1 of them developed sclerosing
      peritonitis. CONCLUSION: The sieving of sodium during CAPD may be caused by
      transcellular water transport. Deficient sieving as assessed by the absence of a
      decreased D/P ratio after one hour of a hypertonic dwell suggests impairment of
      transcellular water transport. This is associated with severe ultrafiltration
      failure. It indicates that failure of transcellular water transport, possibly by
      glycosylation of specific proteins on the cell membrane, may be considered one of
      the causes of ultrafiltration failure during CAPD.

PMID- 7734561
TI  - Subcutaneous epoetin beta in renal anemia: an open multicenter dose titration
      study of patients on continuous peritoneal dialysis.
AB  - OBJECTIVE: To establish dose requirements (target hemoglobin > 100 g/L) and
      safety of subcutaneously administered epoetin beta. DESIGN: Open multicenter
      study. PATIENTS: Forty-five anemic patients (21 female, 24 male; mean age 55
      years; range 20-79 years) who had been on continuous peritoneal dialysis for 1
      157 months (mean 24 months). Thirty patients required blood transfusions during
      the year prior to the study. Mean hemoglobin concentration pretreatment was 75
      g/L (range 57-89 g/L). INTERVENTION: After a pretreatment period of two weeks, 60
      IU kg-1 week-1 divided into three weekly doses of epoetin beta was administered
      subcutaneously. The dose was increased by 60 IU kg-1 week-1 after ten weeks, and
      when necessary, every fourth week in patients with hemoglobin levels below 100
      g/L. MAIN OUTCOME MEASURES: Hemoglobin concentration. Analysis of factors
      affecting the response to epoetin beta. Safety of epoetin beta. RESULTS: Thirty
      eight of the 45 patients completed six months and 21 patients completed one year
      in the study. Twenty-six patients reached hemoglobin 100 g/L within six months
      and 8 patients did later on. The mean hemoglobin concentration after three months
      was 93 g/L (range 64-144 g/L) and after six months was 99 g/L (range 59-130 g/L;
      mean epoetin beta dose 122 IU kg-1 week-1). During the second six-month period of
      the study, hemoglobin levels were stable in most patients. After one year, the
      mean hemoglobin was 110 g/L (range 84-153 g/L) and the mean epoetin beta dose was
      107 IU kg-1 week-1. Prolonged correction time and impaired response to epoetin
      were observed in patients with infections or hemorrhages and in patients with low
      hemoglobin concentration before starting epoetin treatment. Iron deficiency was
      controlled by iron supplementation, either orally or, in 10 patients,
      intravenously. Increased blood pressure, requiring intensified antihypertensive
      treatment, was observed in 13 patients. CONCLUSIONS: Continuous peritoneal
      dialysis patients with moderate anemia (Hb 75-90 g/L) and without complicating
      disorders can be managed with subcutaneous doses of epoetin < 120 IU kg-1 week-1.
      The epoetin beta dose should be adjusted after the first month of treatment since
      most patients required higher doses than the initial 60 IU kg-1 week-1.

PMID- 7734562
TI  - Continuous ambulatory peritoneal dialysis and the heart.
AB  - OBJECTIVE: To review clinical research pertaining to continuous ambulatory
      peritoneal dialysis (CAPD) and the heart. DATA SOURCES: A Medline computer search
      was employed to identify appropriate references from 1970 - 1994. Indexing terms
      were: continuous ambulatory peritoneal dialysis, hemodialysis, heart or cardiac,
      left ventricle, coronary artery disease, and survival. English and non-English
      language abstracts were scrutinized. STUDY SELECTION: Forty-six studies were
      reviewed and utilized. Numerical data extracted are reported in this review as
      they were reported in the original article. RESULTS: This review provides a broad
      based survey of studies pertaining to CAPD and the heart. Most of the studies
      relate to CAPD and left ventricular structure or function. Little information
      exists concerning CAPD and coronary artery disease, valvular disease, pericardial
      disease, and cardiac arrhythmias. Studies pertaining to patient survival on CAPD
      identify coronary artery disease and congestive heart failure as major risk
      factors, but in-depth quantification of these cardiovascular disorders is lacking
      in the literature. CONCLUSIONS: CAPD is capable of decreasing left ventricular
      (LV) volume and improving LV systolic function in patients with LV enlargement
      and those with LV systolic dysfunction. The effect of CAPD on left ventricular
      hypertrophy (LVH) and LV diastolic function is variable. CAPD produces
      symptomatic improvement in patients with refractory congestive heart failure, but
      its effect on survival in such patients is uncertain. Atherogenic lipid
      abnormalities occur in CAPD patients. The clinical significance of these
      abnormalities is uncertain. Coronary artery bypass surgery can be performed
      safely and effectively on CAPD patients. CAPD is not arrhythmogenic. Survival of
      CAPD patients is similar to that of hemodialysis patients except in elderly
      diabetics for whom it is slightly lower.

PMID- 7734563
TI  - Hypomagnesemia in continuous ambulatory peritoneal dialysis patients dialyzed
      with a low-magnesium peritoneal dialysis solution.
AB  - OBJECTIVE: Previous studies have shown a decrease in serum magnesium (Mg)
      concentration when continuous ambulatory peritoneal dialysis (CAPD) patients
      previously maintained on a 1.0-1.2 mEq/L Mg peritoneal dialysis solution (PDS)
      were dialyzed with a 0.5 mEq/L Mg PDS. However, the prevalence of hypomagnesemia
      in CAPD patients dialyzed with low-Mg PDS is unknown. DESIGN: A retrospective
      study to determine the prevalence of hypomagnesemia and the factors associated
      with its occurrence in CAPD patients dialyzed using a 0.5 mEq/L Mg PDS. SETTING:
      A CAPD unit in a large Veterans Affairs Hospital. PATIENTS: All our CAPD patients
      (33) enrolled over a 52-month period. RESULTS: All patients had serum magnesium
      levels higher than 1.25 mEq/L prior to use of low-Mg PDS. Hypomagnesemia (serum
      Mg < 1.25 mEq/L) developed in 21/33 patients (64%) when a 0.5 mEq/L Mg PDS was
      employed. Hypomagnesemia developed a mean of 8.2 months after beginning
      treatments. The duration of dialysis and the number of episodes of peritonitis
      did not differ between patients with and those without hypomagnesemia. Serum
      albumin levels were significantly lower in patients with hypomagnesemia (2.5 +/-
      0.12 g/dL vs 3.2 +/- 0.12, p < 0.01). Magnesium supplements were given to 13
      patients; following this therapy, serum magnesium values became normal.
      CONCLUSIONS: CAPD patients dialyzed with a 0.5 mEq/L Mg PDS may develop a
      considerable fall in serum magnesium level and may require magnesium supplements
      in order to restore normal serum values.

PMID- 7734564
TI  - Effect of oral calcidiol treatment on its serum levels and peritoneal losses.
AB  - OBJECTIVES: To evaluate calcidiol serum levels in a group of continuous
      ambulatory peritoneal dialysis (CAPD) patients and the effect of oral calcidiol
      treatment on serum levels and peritoneal losses. STUDY DESIGN: Twenty patients
      (13 female, 7 male) were studied for 12-60 months. Their ages ranged 22-72 years
      (mean 46 +/- 15). Serum calcidiol, total protein and urea were determined at
      baseline and after the administration per os of 0.133 mcg/day of calcidiol for 10
      days. At the same time, calcidiol and total protein were measured in peritoneal
      effluent at baseline and at 5, 10, and 40 days after starting this treatment.
      RESULTS: A significant and direct correlation between the calcidiol
      dialysis/plasma ratio and the peritoneal protein losses was found, both before
      and 40 days after calcidiol administration when calcidiol serum levels were the
      lowest. As calcidiol serum levels rose to the normal range in the course of the
      study, peritoneal losses of this metabolite increased slightly and correlated
      with calcidiol serum levels and urea mass transfer coefficient (MTC); the
      significant correlation between calcidiol serum levels and peritoneal protein
      losses disappeared. CONCLUSIONS: When serum calcidiol levels are low, calcidiol
      peritoneal losses in patients on CAPD correlate with protein peritoneal losses.
      However, when serum calcidiol levels rise, the calcidiol peritoneal losses
      correlate with calcidiol serum levels and urea MTC, and not with protein
      peritoneal losses.

PMID- 7734565
TI  - Successful reinstitution of CAPD after retroperitoneal repair of an aortic
      aneurysm: a case report.

PMID- 7734566
TI  - Stability of ofloxacin in peritoneal dialysis solutions.

PMID- 7734567
TI  - Acquired cystic disease mimicking polycystic kidney disease in a long-term CAPD
      patient.

PMID- 7734568
TI  - Eosinophilic peritonitis and drug-induced lymphocyte transformation in vitro.

PMID- 7734569
TI  - Successful antifungal prophylaxis in chronic peritoneal dialysis: a pediatric
      experience.

PMID- 7734570
TI  - Intraperitoneal inflammation after previous contact with killed microbes.

PMID- 7734571
TI  - Protective effect of hyaluronic acid against peritoneal injury.

PMID- 7734572
TI  - Vaginal fistula: a new complication in CAPD.

PMID- 7734573
TI  - Vaginal peritoneal dialysate leakage per fallopian tubes.

PMID- 7734574
TI  - Mannitol-induced acute renal failure successfully treated with peritoneal
      dialysis.

PMID- 7734575
TI  - Exit site-tunnel infection rate in Tenckhoff catheter with a 2.3 diameter exit
      site-tunnel section.

PMID- 7734576
TI  - The effect of temperature and glucose concentration on the growth of
      microorganisms commonly associated with CAPD peritonitis.

PMID- 7734577
TI  - CAPD peritonitis due to Corynebacterium striatum.

PMID- 7734578
TI  - Peritonitis due to Clostridium septicum in a CAPD patient.

PMID- 7734579
TI  - Literature. October-December 1994.

PMID- 7734580
TI  - Preference and requests for smoke-free dining.
AB  - This study looked at whether people prefer to sit in smoking or smoke-free areas
      when they go to cafes and restaurants. It also considered whether those who said
      they would prefer smoke-free dining made this known when booking or going to a
      restaurant. The sample was 2387 Victorians, randomly selected and interviewed in
      their own homes. Overall, 68 per cent of respondents said they would prefer a
      nonsmoking area, and only 11 per cent preferred a smoking area. Even among
      smokers, less than half (42 per cent) wanted to sit in a smoking area. Of those
      people who wanted smoke-free dining, only 45 per cent said they always made this
      known. The results demonstrate strong community desire for smoke-free dining, but
      also point to the need for restaurant managers or the dining public to take the
      initiative, or for legislative action to ensure the provision of smoke-free
      areas.

PMID- 7734581
TI  - A glimpse at public health in Eastern Europe.

PMID- 7734582
TI  - Impressions of public health in Germany and Europe.

PMID- 7734583
TI  - Changing definitions till the cows come home.

PMID- 7734584
TI  - Routine HIV testing before surgery.

PMID- 7734585
TI  - Immunisation against Haemophilus influenzae type b.

PMID- 7734586
TI  - Heterosexual behaviour and HIV risk in New Zealand: data from a national survey.
AB  - The pattern of any future major heterosexual epidemic of acquired
      immunodeficiency syndrome (AIDS) will depend partly on sexual behaviour and
      condom use among heterosexuals. This survey was designed to provide information
      on patterns of sexual behaviour in New Zealand. A national sample aged 18 to 54
      was selected using a random method and telephone interviews were administered to
      2361 people, using a questionnaire based on the protocol developed by the Global
      Program on AIDS of the World Health Organization. The reported mean lifetime
      number of partners increased with age up to 25 to 29 years for women and 30 to 34
      years for men, and declined at older ages. Fifteen or more lifetime partners were
      reported by 17 per cent of men and 4 per cent of women. Multiple partnerships in
      the previous 12 months were commonest in those aged 20 to 24. In this age group,
      32 per cent of men and 20 per cent of women reported two or more partners. Recent
      condom use for contraception was reported by 23 per cent of men and 19 per cent
      of women. Use was highest amongst those aged 18 to 24, and decreased sharply with
      age. The true proportion of the population with many sexual partners may be
      higher than reported. These data will be useful in modelling approaches to
      estimate the likelihood of future heterosexual spread of AIDS. The data on
      lifetime numbers of partners suggest that sexual decisions depend not just on age
      and sex but also on the era, and thus on changing social values about sexual
      behaviour.

PMID- 7734587
TI  - Colorectal cancer and its prevention: prevalence of beliefs, attitudes,
      intentions and behaviour.
AB  - There is so far only limited evidence from randomised controlled trials that
      screening for colorectal cancer using the faecal occult blood test produces
      significant mortality reductions in screened groups, but there is considerable
      activity and interest in the use of such screening in Australia. Beliefs,
      attitudes, intentions and behaviour in relation to colorectal cancer and
      screening were examined among participants 40 years and older (n = 1776) who took
      part in a representative population survey. While there were high levels of
      awareness of faecal occult blood test screening, most respondents had not had a
      test, nor did they intend to take a test in the future. Important determinants of
      participation in screening were a family history of colorectal cancer, a belief
      that bowel cancer can be cured if detected at an early stage, a perception of
      personal susceptibility to bowel cancer and an acceptance of the technique.
      Factors such as these are likely to influence the success of any future screening
      program in Australia.

PMID- 7734588
TI  - The potential benefits and harms of screening for colorectal cancer.
AB  - Australian guidelines for colorectal cancer screening for average-risk
      populations vary from recommendations for annual screening by faecal occult blood
      testing for those over 40 years to recommendations that screening may be
      appropriate if requested by an informed patient aged 50 to 75 years. There are
      five large screening trials, of which three have published mortality data. A meta
      analysis of the mortality data suggests a 19 per cent reduction in colorectal
      cancer mortality (95 per cent confidence intervals 0.68 to 0.96) with Hemoccult
      screening. Because of the width of the confidence interval, decisions about the
      magnitude of the effect of screening should await further trial results, which
      should be available in the next few years. In the interim, we should examine
      issues of harm and costs in Australia. For example, in the major trials, over 80
      per cent of positive results have been falsely positive and have required
      invasive investigation. Estimates of the cost-effectiveness of screening for the
      Australian health system are not yet available and are essential. If the benefits
      of screening outweight the harms and costs, a successful screening program would
      require provision of screening infrastructure and appropriate information to
      target populations, quality control for screening tests and investigations,
      recall mechanisms to ensure appropriate follow-up of persons with positive
      results and the active participation of the Australian public and health
      practitioners.

PMID- 7734589
TI  - Smoking by adolescents: large revenue but little for prevention.
AB  - The purpose of this paper is to report on the government revenue gained from the
      sale of cigarettes to minors and the proportion of this revenue that is spent on
      attempting to prevent adolescents from taking up this habit. Prevalence of
      smoking by minors was extrapolated for the individual states using Australian
      prevalence data; estimates of annual cigarette consumption were coupled with the
      respective cost of cigarettes in each state to derive an estimate of the total
      revenue accumulating from cigarette consumption by minors. From our analysis,
      approximately 211,000 Australian children under the legal age to purchase
      cigarettes consumed approximately  11.5 million packets of cigarettes in 1990.
      The estimated tax revenues to the federal and state governments from these sales
      were $8.42 million and $12.78 million respectively. While the average state
      revenue from cigarette consumption by minors during 1990 was just over $60 per
      under-age smoker, only $0.11 per under-age smoker was spent on anti-smoking
      campaigns in 1990. This is equivalent to approximately 0.002 per cent of state
      revenue from cigarette smoking by those under the legal purchase age being spent
      on discouraging adolescents from taking up this habit. Clearly, there is an
      inequitable expenditure on antismoking activities, given the enormous resources
      obtained from sales to minors.

PMID- 7734590
TI  - Beyond the maze.

PMID- 7734591
TI  - Development of sample size models for national general practice surveys.
AB  - The most cost-effective method to measure the morbidity managed and treatments
      provided in general practice is from records of a cluster of consultations
      (encounters) from each general practitioner (GP) in a random sample. A cluster
      sampling method is proposed for future surveys for analysis of encounter-based
      general practice data. The sample sizes needed to measure the most common
      problems managed and drugs prescribed were estimated using ratio-estimator models
      for cluster sample surveys. Morbidity and treatment rates were estimated from the
      Australian Morbidity and Treatment Survey in General Practice 1990-1991 (AMTS).
      The 20 most common problems in the AMTS were managed at estimated rates of 1.5 to
      9.5 per 100 encounters. The 20 most common drugs were prescribed at estimated
      rates of 0.7 to 3.6 per 100 problems. These rates were used to determine
      precision as a percentage of each true value for future surveys, that is, as
      relative precision. If we want to be 95 per cent confident that these rates will
      be within 5 per cent of each true rate, sample sizes of 552 to 5675 GPs are
      needed. If we fix the sample size at 1000 GPs, relative precision lies within 12
      per cent of these rates. If the sample size is increased to 1500 GPs, relative
      precision improves only marginally. The differences in sample size for each of
      the most frequent morbidity and treatment data are largely due to their variable
      distributions and relatively infrequent occurrence in general practice. A sample
      size of 1000 GPs will enable measurement of the most common morbidity and
      treatments at 95 per cent confidence.

PMID- 7734592
TI  - Alcohol consumption and harm in two Western Australian regional centres.
AB  - The application of national or state alcohol harm-prevention programs at a
      regional level can be inappropriate. The involvement of local communities is
      critical if harm-prevention responses are to be sensitive to local needs.
      Unfortunately, individuals and agencies usually have little idea of the impact of
      alcohol at the local level. Alcohol consumption and harm data have been gathered
      for Geraldton and Bunbury, two regional centres of comparable size in Western
      Australia. The indices of harm presented include the nature and cost of hospital
      morbidity attributable to alcohol, and drink-driving charges. In Geraldton, the
      impact of alcohol tends to be acute and affects young adults, particularly young
      males. In Bunbury, the consequences of alcohol use tend to be more chronic in
      nature and affect older adults. These findings have been used to inform local
      harm-prevention responses, but more than that, this study is a practical example
      of how available data can be aggregated at a community level to illustrate local
      alcohol use and harm. This method can be replicated in any community that wants
      to understand better the effects of alcohol in its own local context.

PMID- 7734593
TI  - Work-related deaths of children and adolescents in Australia, 1982 to 1984.
AB  - Work-related deaths of children and adolescents up to the age of 19 years were
      studied as part of a larger investigation into all work-related fatalities in
      Australia in the three-year period, 1982 to 1984. This study aimed to
      characterise the circumstances which led to the deaths of these children. Of 1738
      work-related fatalities identified over the three years in the larger
      investigation, 67 (4 per cent) were aged under 15 years, and 117 (7 per cent)
      were aged 15 to 19 years. The fatalities were characterised by a number of
      variables, the most important being age, sex, bystander status, location (farm or
      other) and vehicle involvement (especially tractors). The causes of death
      differed between subgroups. Although existing controls may be reasonably
      effective in minimising child deaths in most work places, farms are an exception.
      On farms, home and work activities overlap, and informal participation in work by
      the young is quite common. Preventive efforts should give special attention to
      farms and tractors, to toddlers and male children, and to measures (such as
      safety devices and other external control measures) which do not rely on
      behavioural change in the young people at risk. Adults responsible for young
      children should be educated to anticipate dangerous situations and thus ensure
      children are protected from injury hazards.

PMID- 7734594
TI  - Oral health care in Australia--a public health perspective.

PMID- 7734595
TI  - Homicide in New Zealand: an increasing public health problem.
AB  - Injury purposely inflicted by other persons is a significant public health
      problem as well as a criminal problem. It accounts for approximately 3 per cent
      of all deaths from injury in New Zealand. National injury mortality data for the
      period 1978 to 1987, supplemented by reference to files of the Coroner's Court
      and the High Court, were used to identify the characteristics of victims of
      homicide, the nature of the injuries they sustained, and the circumstances in
      which the injuries were inflicted. The mortality rate from homicide for the 10
      year period was 1.6 per 100,000 persons per year. A significant increase in the
      rate of homicide was identified. The rates for males were higher (2.0) than those
      for females (1.2), with those 20 to 24 years of age most at risk. Maori had
      higher rates than non-Maori. Homicides were most frequently committed with
      cutting and piercing instruments, and most commonly occurred in private homes.
      Homicides were most likely to occur on Fridays or Saturdays, between the hours of
      6 p.m. and 6 a.m. In 55 per cent of homicides the victim and assailant were known
      to one another. Unemployment, membership of ethnic minority groups, availability
      of weapons, the private nature of interactions in the home, alcohol consumption,
      and stress in personal relationships were all identified as factors associated
      with homicide in the decade under study. The implications of these findings for
      the prevention of injury from assault are discussed.

PMID- 7734596
TI  - A retrospective cohort study of childhood immunisation status in northern Sydney.
AB  - A survey of their children's immunisation status was conducted among mothers of
      babies from a three-month birth cohort (January to March 1990) in the Northern
      Sydney Area in 1992. Its aims were to determine the uptake of immunisation in the
      area, to examine factors associated with immunisation status, and to assess
      agreement between the parent's reporting of this status and records of councils
      and general practitioners. Fifty-eight per cent of the questionnaires (1004) were
      returned. The full immunisation rate was 86 per cent, 14 per cent were partially
      immunised and only four children had received no immunisations. Between 74 per
      cent and 82 per cent of vaccinations were on time at two, four and six months;
      the rate dropped to 21 per cent at 12 months. Logistic regression analysis showed
      that premature babies are significantly more likely to be fully immunised,
      whereas children who have had a serious childhood illness, those with a single
      mother, or whose mothers are more highly educated, are significantly less likely
      to be fully immunised. There was 60 per cent agreement between the parent's
      report of immunisation status and a subgroup of 197 council and 82 general
      practitioner records. Although all councils in the Northern Sydney Area have a
      reminder system, most immunisations were found to be done in general practices
      (64 per cent), where reminder systems are not common.

PMID- 7734597
TI  - Dietary behaviours of volunteers for a nutrition education program, compared with
      a population sample.
AB  - The dietary behaviours of and recent dietary change by volunteers for a nutrition
      education program were compared with those of a more population-representative
      sample. The population sample was randomly selected from the electoral rolls of
      three Australian cities. Those selected received questionnaires which were to be
      completed and returned by mail. The sample of volunteers was recruited from the
      electoral rolls of suburbs of either high or low social status in one of these
      cities. Volunteers were posted a questionnaire, to be returned in person. A
      quantified food frequency questionnaire was used to estimate relative intake of
      19 nutrients, plus energy intake. Occupation, age, sex, reported recent dietary
      change and diet-related beliefs were also assessed. The population sample was
      weighted to the age and occupational distribution of the education program
      sample. Compared to the 874 respondents in the population sample (70.4 per cent
      response rate), the 487 volunteers (24.2 per cent response rate) for the
      nutrition education program had healthier nutrient intakes and reported more
      dietary behaviour changes. Recruitment in the education program was greater in
      areas of higher social status (32 per cent) than in areas of lower social status
      (20 per cent). The potential effect of such a program on the whole population was
      demonstrated by the proportions that volunteered and the characteristics of these
      volunteers. The need to provide a range of opportunities for changing dietary
      behaviour, according to the health-related behaviours and beliefs of target
      groups and their socio-economic circumstances, was highlighted.

PMID- 7734598
TI  - Leisure-time physical activity and other health behaviours: are they related?
AB  - Data on the associations between leisure-time physical activity and other health
      behaviours are conflicting. The National Heart Foundation 1989 Risk Factor
      Prevalence Survey data were analysed to examine the associations between leisure
      time physical activity and other life-style health behaviours in a national
      representative sample with adjustment for potential confounders. Multivariate
      stepwise logistic regression analysis using data from 9054 respondents aged 20 to
      69 years showed that participation in leisure-time physical activity, even when
      it was not vigorous, was weakly associated with not smoking, following a special
      diet and moderate consumption of alcohol; it was inversely associated with
      obesity. These weak associations could influence health practices at a population
      level if, as has been hypothesised, the adoption of leisure activity promotes the
      adoption of other good health practices. Confirmation of earlier findings of
      cross-sectional associations between activity and other positive health practices
      justifies future prospective or experimental studies to determine the behavioural
      response to adoption of leisure-time physical activity.

PMID- 7734599
TI  - Elkington and after: public health, Queensland style.

PMID- 7734600
TI  - The seasonality of hip fracture and its relationship with weather conditions in
      New South Wales.
AB  - The seasonal pattern in hip fracture rates and its relationship to weather
      variables was studied using hospital admission data for New South Wales. There
      was a consistent seasonal pattern for hip fracture, with a trough in the summer
      and a peak in the winter, for the six years for which data were available: 1981,
      1983, 1986, 1988, 1989 and 1990. The seasonal trends for all years were
      statistically significant (P < 0.01) in men and in women, and in people who were
      75 years and over. The relationship between the monthly admission rates for hip
      fracture in Sydney and such weather variables as mean daily minimum temperature,
      mean cloud cover, number of days with strong wind, number of days of fog, number
      of days of mist and number of days with 0.1 mm or more rainfall in a month were
      studied by Poisson regression. The mean daily minimum temperature for each month
      was the single weather variable independently and consistently associated with
      the monthly rates of hip fracture in both younger and older people. For the first
      time, a seasonal pattern for hip fracture and its close association with monthly
      temperature in Australia has been demonstrated.

PMID- 7734601
TI  - Social inequality in the use and comprehensiveness of dental services.
AB  - Fair access is a value enshrined through universal insurance for health care in
      Australia. However, dentistry is not included in this system. As a consequence,
      there is a strong likelihood of inequalities in access to dental services among
      adults. Data from the 1989-90 National Health Survey were analysed to determine
      sociodemographic factors related to use and comprehensiveness of dental services.
      Age, income, age of leaving school and occupation were independently associated
      with the use of dental services, and occupation was associated with an indicator
      of comprehensiveness of care: self-reported extraction at the last visit. In
      different adult age groups these sociodemographic factors had different effects,
      with the disparities in use of dental services greater in older age groups.
      Planning of dental services in the 1990s and beyond should include not only the
      removal of financial barriers to dental services among adults but also attention
      to the specific barriers experienced by the elderly.

PMID- 7734602
TI  - Skin examination for signs of cancer.
AB  - Doctors sometimes examine or suggest examination of the skin for signs of skin
      cancer, and self-examination of the skin has been promoted in some public
      education materials. A representative sample of 590 residents of Victoria was
      asked whether they or their doctors had ever deliberately checked for signs of
      skin cancer, and whether their doctors had ever suggested such a check.
      Respondents also indicated their skin type by degree of freckling and propensity
      to sunburn. The results suggest that females have a higher level of skin
      awareness than males. People prone to sunburn and heavily freckled individuals
      were more likely to have checked their skin, and doctors were more likely to have
      suggested a check to highly freckled individuals. Self-examination, examination
      by a doctor and recommendations from doctors for self-examination were all
      positively associated with each other, indicating that a section of the
      population was identified by themselves or their doctors as being at risk, but
      this group was not well defined by the two indices of risk used in the survey.

PMID- 7734603
TI  - Disinfection of drinking water, disinfection by-products and cancer: what about
      Australia?
AB  - Chlorine, commonly used to disinfect drinking water, produces by-products known
      from animal studies to be carcinogenic and mutagenic. Most epidemiological
      studies into the possible association between chlorination by-products in
      drinking water and cancer have been ecological in nature, or have relied on case
      control designs based on death certificates. Interpretation of results arising
      from these studies is limited. Individual levels of toxicant exposure and many
      potential confounders and effect modifiers are unable to be accounted for in the
      analyses. At best, these studies generate hypotheses that require more definitive
      investigation. Misclassification of individuals based on inaccurate assessment of
      the level of exposure is probable. The few analytic studies able to overcome or
      minimise these problems suggest a clear link between exposure to chlorinated
      drinking water and the development of urinary bladder cancer. They also suggest a
      possible link with rectal cancer. However, these studies have classified subjects
      by exposure to chlorinated drinking water, rather than to levels of chlorine and
      its by-products in drinking water. To date, the link between levels of chlorine
      and its by-products in water, levels of consumption and cancer has not been made.
      Information on the levels of chlorine and some by-products is available in many
      water jurisdictions in Australia. Further, epidemiological methods can be
      employed to quantify water consumption. Case-control studies linking these
      parameters would help us to understand the magnitude of the risk to human
      populations and provide a basis to investigate mechanisms for risk reduction.

PMID- 7734605
TI  - Inpatient cervical screening: a survey of patient acceptability.
AB  - Offering Pap tests to hospital inpatients could increase cervical screening
      rates. A survey to examine the acceptability of this concept was conducted with
      female inpatients in a rural public hospital. A large majority reported that they
      would find hospital Pap tests acceptable. Acceptability was not related to Pap
      test status, attitudes, or knowledge of cervical cancer. This strategy may
      provide access to cervical screening for underscreened groups.

PMID- 7734604
TI  - When you can't ask their names: linking anonymous respondents with the Hogben
      number.
AB  - This article describes a method of linking anonymous subjects with a respondent
      generated code using an algorithm based on personal details to produce unique
      identifiers. It was used to increase confidentiality and statistical power in a
      year-long work-place health promotion evaluation. Subjects were employees of a
      large retail chain; 80 per cent were female, and the majority educated to high
      school level. Of the 385 possible, 81 per cent matched; 67 per cent of the codes
      were matched on all elements and another 14 per cent were accepted as 'fuzzy'
      matches. Linking respondents increased the statistical power of the study from an
      unacceptable 0.4 to an acceptable 0.8. Other research on linking records is
      briefly discussed, including sample bias and probabilistic matching. This
      technique is useful when anonymity is likely to raise response rates, but the
      ideal code could be further sought.

PMID- 7734606
TI  - Smoking in hotels: prevalence, and opinions about restrictions.
AB  - Exposure to high levels of environmental tobacco smoke can occur in hotels.
      Controversy exists about smoking regulation on licensed premises. This survey of
      138 people attending one of three Newcastle hotels during 1993 found that 57 per
      cent of respondents were nonsmokers. Fifty-eight per cent (95 per cent confidence
      interval (CI) 50 to 66 per cent) of respondents in these hotels believed their
      health was being adversely affected by other people's smoke in the hotel. Seventy
      per cent (CI 62 to 78 per cent), including half the smokers, were in favour of
      restriction of smoking in the hotels. Most preferred the establishment of smoke
      free areas to the introduction of total smoking bans in hotels. The failure of
      hotels to regulate smoking suggests that a legislative approach is required. The
      case for legislation would be strengthened by a larger study elsewhere in
      Australia.

PMID- 7734607
TI  - Prevalence and correlates of depressive syndromes among adults visiting an Indian
      Health Service primary care clinic.
AB  - Depression is common among patients visiting primary care clinics. In order to
      describe the prevalence of depressive syndromes in an American Indian primary
      care clinic population and to help define the clinical correlates of depressive
      syndromes in this setting, a clinic-based research study of depression was
      undertaken by the Indian Health Service (IHS). One hundred and six patients from
      an IHS primary care clinic were systematically enlisted for participation in the
      study. Participants completed the Inventory for Diagnosing Depression (IDD).
      Twenty-two (20.7%) responded with answers scoring positive for a depressive
      syndrome. Nine of these 22 (8.9% of the 106 participants) met IDD criteria for a
      major depressive syndrome. A diagnosis of depression, a past history of
      depression, use of mental health facilities, unexplained pains, and
      antidepressant medication use were associated with the presence of a depressive
      syndrome.

PMID- 7734608
TI  - The dilemma of mental health paraprofessionals at home.
AB  - The use of community member paraprofessionals in the delivery of mental health
      services is complicated by the changing nature of the paraprofessional's social
      relationships within the community. We use an anthropological model of Coast
      Salish social organization and data from a current delivery system, the Swinomish
      (Washington) Tribal Mental Health Project, to suggest ways to conceptualize and
      account for such complications.

PMID- 7734610
TI  - Mental health and American Indian women's multiple roles.
AB  - The author's purpose in conducting this study was to identify the relationship of
      sex role orientation to indices of psychological well-being among 148 American
      Indian working women from the Midwest. Analyses revealed that the sex-typed group
      had significantly higher depression scores, higher role conflict scores, lower
      self-esteem scores and lower life satisfaction scores when compared with the
      cross-typed and androgynous groups. The undifferentiated group had significantly
      lower self-esteem scores when compared with the androgynous group. Further
      research is needed to understand how different sex role orientations support
      different roles that American Indian women occupy.

PMID- 7734609
TI  - Group therapy of aboriginal offenders in a Canadian forensic psychiatric
      facility.
AB  - In recent years, the use of group therapy approaches with Aboriginal or Native
      Canadians/American Indians has become widely accepted. However, many advocates of
      this approach rarely consider the implications of group therapy for culturally
      heterogeneous groups, such as when non-Aboriginal peoples are involved or when
      there are Aboriginal peoples from different cultures and/or with different
      degrees of orientation to Euro-Canadian culture. This article documents the use
      of one form of group therapy for Aboriginal offenders in a forensic psychiatric
      facility, where this degree of cultural heterogeneity exists. The article
      concludes that, at least within a forensic psychiatric setting, group therapies
      that mirror the social, cultural, racial, and class structures of Euro-Canadian
      society are problematic in the treatment of traditional Aboriginal offenders but
      much less so for acculturated Aboriginal offenders.

PMID- 7734611
TI  - [Isolation and study of certain properties of caldesmon from cattle aorta].
AB  - A modified method for bovine aorta caldesmon isolation has been developed. When
      isolated from large vessels, caldesmon is copurified with connective tissue
      proteins whose molecular weight is similar to that of caldesmon. Separation of
      these proteins can be achieved by stepwise anion- (Q-Sepharose) and cation
      (phosphocellulose)-exchange chromatography. Bovine aorta and duck gizzard
      caldesmons have similar apparent molecular weights, absorption at 280 nm and one
      dimensional peptide maps. Casein kinase II transfers about one mol of phosphate
      per mol of bovine aorta or duck gizzard caldesmon. In both cases, the sites of
      phosphorylation are located in the N-terminal peptides of apparent molecular
      weights of 26-28 kDa. It is concluded that there are no substantial differences
      between the structures and properties of avian gizzard and mammalian vessel
      caldesmons.

PMID- 7734612
TI  - [Modern representations of multiple forms of cyclic nucleotide phosphodiesterases
      in mammalian tissues].
AB  - The literary data from the past 10-15 years concerning cyclic nucleotide
      phosphodiesterase from animal tissues have been reviewed. The major properties of
      multiple forms of the enzyme differing in the mode of regulation, substrate
      specificity, physico-chemical parameters and primary structure are compared. The
      possible physiological role of the main phosphodiesterase forms and ways of their
      pharmacological regulation are discussed.

PMID- 7734613
TI  - [Interaction of Escherichia coli RNA polymerase with promoters. The need for a
      classified approach in studying the code of promoter-polymerase recognition].
AB  - The data on E. coli RNA polymerase (E sigma 70) interaction with its numerous
      promoters are reviewed. Two different approaches to the problem of promoter
      polymerase recognition code are analyzed. One approach is consistent with the
      idea of a universal code on the basis of a consensus promoter. According to this
      approach, the unique active center in the enzyme is involved in interaction with
      all promoters. The second approach is based on the original concept suggesting
      the existence of several active centers in RNA polymerase, each of them
      interacting with its own group of promoters. This approach is based on the idea
      that promoter-polymerase recognition is coded by different programs for different
      groups of promoters; therefore, the problem should be contemplated from the
      standpoint of a classification analysis of promoters. Supporting evidence in
      favour of this concept is presented.

PMID- 7734614
TI  - [Study of the structure and mechanism of action of troponin C and calmodulin by
      "protein" engineering].
AB  - The structure, properties and action mechanisms of troponin C and calmodulin are
      reviewed. The primary and tertiary structures of calcium-binding proteins and the
      mechanisms of Ca2+ binding are analyzed. The methods used for investigating the
      functional activity of Ca-binding proteins are compared. Molecular biology
      approaches for analyzing the role of various ligands in Ca2+ binding are
      described. The role of alpha-helices in the maintenance of the overall structure,
      Ca2+ binding and calmodulin and troponin C interaction with target proteins is
      discussed. Mutations directed at the change of the electric charge and
      hydrophobicity of calmodulin and troponin C are described and compared. Data on
      the incorporation of Cys residues into calmodulin and troponin C structure are
      presented. The use of Cys-containing mutants of Ca-binding proteins for the study
      of conformational changes and protein-protein interaction is analyzed.

PMID- 7734615
TI  - [Glycosyltransferase inhibitors and study of UDP-galactose-globoside
      galactosyltransferase].
AB  - There is now a large body of evidence indicating that glycoconjugates are
      involved in a wide variety of processes that influence cell growth,
      differentiation, cell sociological behavior and response to environmental
      conditions. The synthesis and expression of this class of compounds appears to be
      regulated to a large extent by the activities of the glycosyltransferases which
      are responsible for their biosynthesis. The level of glycosyltransferase
      activities in cells could be regulated at many levels. Thus, factors that
      influence transcription and splicing of the transferase genes, stability of the
      mRNAs, translation, and post-translation processes are all probably involved.
      Post-translation processes that affect the level of enzyme activity could include
      proteolytic degradation, glycosylation, phosphorylation, sulfation, acylation,
      and the presence of activator and inhibitory factors. Although the presence of a
      least seven different glycosyltransferase inhibitors have been reported, this
      type of regulation has received relatively little attention. It appears from the
      data cited in this review that in many instances, cellular inhibitors of
      glycosyltransferase activities may play a key role in the regulation of
      transferase activities and the expression of glycoconjugates. This type of post
      translational regulation of glycosyltransferase activities deserves increased
      attention.

PMID- 7734617
TI  - [Energy status of rat liver during the dynamics of cold adaptation].
AB  - The energy state of rat liver at various times of cold acclimation has been
      studied. On day 10 of cold exposure, the energy state of the liver is
      characterized by a low level of ATP and the adenine nucleotide pool as well as by
      low values of the phosphorylation potential and the "energy charge". The
      respiratory control is decreased, while the low permeability of the inner
      mitochondrial membrane is increased. It is supposed that on days 10-15 after cold
      exposure the liver becomes actively involved in thermal stabilization. Cold
      acclimation on days 35-42 leads to an increase in State 3 respiration rate,
      respiratory control and energization of liver mitochondria. This allows to
      maintain the ATP level and the total adenine nucleotide pool in liver tissues at
      the control level. However, this does not seem to compensate completely for the
      energy expenditure because the phosphorylation potential and the "energy charge"
      of the liver are thereby decreased.

PMID- 7734616
TI  - [The role of the adenine nucleotide carrier in regulating energy and ion
      permeability of rat liver mitochondria upon cold exposure].
AB  - The energy state of rat liver mitochondria on day 10 of cold acclimation, when
      the body temperature decreases significantly concomitantly with an increase in
      the content of long-chain acyl-CoAs in the liver, has been studied. State 4 and
      uncoupling respiration rates increase in parallel; however, the integral
      potentials of the adenine nucleotide system in the liver diminish. In the
      presence of oligomycin, ADP (20 and 50 microM) decreases the II(+)-permeability
      and increases the Ca(2+)-capacity of mitochondria in both control and, in a
      lesser degree, cold-exposed rats. At 90 microM ADP has the same effect on
      mitochondria of both groups of rats. Carboxyatractylate abolishes the ADP effect
      on the mitochondria. In EGTA-containing media carboxyatractylate decreases the
      respiration rate in oligomycin-treated mitochondria. Palmitoyl-CoA increases the
      II(+)-permeability of the mitochondrial membrane and decreases the Ca(2+)
      capacity of mitochondria. ADP abolished the competitive effects of this long
      chain acyl-CoA. Possible involvement of the ATP/ADP antiporter in the
      thermoregulatory response of liver mitochondria in cold-acclimated rats and the
      role of fatty acids and long-chain acyl-CoAs in this process are discussed.

PMID- 7734618
TI  - [Nuclease isoforms of natural and recombinant strains of Serratia marcescens.
      Comparative characteristics of plasma desorption mass spectrometry].
AB  - The primary structure of isoforms of natural nuclease secreted by Serratia
      marcescens as well as of recombinant nuclease produced by Escherichia coli has
      been characterized by plasma desorption mass spectrometry. The isoforms were
      isolated from the purified nuclease on a DEAE-cellulose anion-exchange column and
      digested with endoproteinase Lys-C. The peptides generated were isolated by
      reversed phase IIPLC and their molecular masses determined by plasma desorption
      mass spectrometry. Among the nuclease isoforms secreted by parent cells, a new
      isoform, Sm3, was found. Comparison of the peptides yielded by nuclease Sm2 and
      two isoenzymes, Sm1 and Sm3, demonstrated their distinction only in the N
      termini; three amino acids are lacking in Sm1 and one residue in Sm3. Identity
      was demonstrated between nucleases Sm1 and Sm2 produced by S. marcescens and the
      isoforms rSm1 and rSm2 secreted by the recombinant E. coli strain.

PMID- 7734619
TI  - [Characteristics of isoforms of Serratia marcescens from electrospray mass
      spectrometry].
AB  - Electrospray mass spectrometry was used to determine the molecular masses of
      nuclease isoforms isolated and purified from the cultural fluid of Serratia
      marcescens B10M1. The primary structure of each of the isoforms isolated from the
      nuclease preparations was established by comparing their masses with the known
      amino acid sequence encoded by the nuc-gene. The structure of some of these
      isoforms was verified by N-terminal sequencing, that of nearly all isoforms-by
      isoelectric focusing. All nuclease isoforms were found to be variants of native
      nuclease split at the molecular N-termini.

PMID- 7734620
TI  - [Study of the substrate specificity of T4 RNA ligase: interaction of the enzyme
      with ATP analogs modified through the ribose residue and with affinity sorbents].
AB  - To elucidate the role of the ribose moiety in substrate binding, various ATP
      derivatives modified in ribose moiety were studied as probes for the T4 RNA
      ligase first stage reaction. The kinetic parameters for competitive inhibition
      were determined. Inhibition experiments using substrate analogs demonstrated that
      the major binding determinants of ATP analogs were purine and triphosphate
      moieties of ATP; modification of the ribose moiety was not critical. Adenosine
      triphosphates attached to agarose were used as affinity adsorbent for
      purification of T4 RNA ligase. These derivatives had been successfully used in
      reversible binding of the enzyme. Best results were achieved with agarose coupled
      via N6 of the purine moiety of ATP.

PMID- 7734621
TI  - Cell cycle analysis by the relative movement approach: effect of variability
      across S-phase of DNA synthesis rate.
AB  - Cell populations pulse-labelled with BrdUrd, and sampled at increasing times
      after the pulse, yield DNA-BrdUrd distributions from which the relative movement
      (RM) and the depletion function (DF) of labelled, undivided cells can be
      calculated. In this paper we present an extension of the equation for the time
      course of RM, given by White and Meistrich (Cytometry 1986, 7, 486-490), to the
      case in which the rate of DNA synthesis changes across S-phase. Some modalities
      of cell loss were also considered. Computer simulations showed that different
      patterns of DNA synthesis rate across S-phase can result in appreciably different
      RM curves. An analytical expression of the RM curve, in which the variability
      across S-phase of the rate of DNA synthesis is accounted for by only one
      parameter, was proposed. This expression was used for the simultaneous fitting of
      time sequences of RM and DF data of U937 cells, in order to estimate the phase
      transit times TS and TG2+M, and the potential doubling time Tpot. The use of the
      extended model gave better results than those obtained under the assumption of
      constant rate of DNA synthesis across S-phase.

PMID- 7734622
TI  - cAMP and PMA enhance the effects of IGF-I in the proliferation of endometrial
      adenocarcinoma cell line HEC-1-A by acting at the G1 phase of the cell cycle.
AB  - The present study was undertaken to determine whether endometrial cancer cell
      line HEC-1-A differ from nontransformed cells, in that the cAMP and protein
      kinase C pathways may enhance IGF-I effects in mitogenesis by acting at the G1
      phase of the cell cycle instead of G0. Immunofluorescence staining of HEC-1-A
      cells using the proliferating cell nuclear antigen (PCNA) monoclonal antibody and
      flow cytometric analysis determined that HEC-1-A cells do not enter the G0 phase
      of the cell cycle when incubated in a serum-free medium. Approximately 51% of the
      cells were in G1, 12% were in S and 37% in G2 phase of the cell cycle prior to
      treatment. Forskolin and phorbol-12-myristate 13-acetate (PMA) were used to
      stimulate cAMP production and protein kinase C activity, respectively. IGF-I,
      forskolin and PMA each increased (P < 0.01) [3H]-thymidine incorporation in a
      dose and time dependent manner. The interaction of forskolin and PMA with IGF-I
      was then determined. Cells preincubated with forskolin or PMA followed by
      incubation with IFG-I incorporated significantly more (P < 0.01) [3H]-thymidine
      into DNA than controls or any treatment alone. It is concluded that forskolin
      and, to a lesser extent, PMA exert their effect at the G1 phase of the cycle to
      enhance IGF-I effects in cell proliferation.

PMID- 7734623
TI  - A quantitative method for the analysis of mammalian cell proliferation in culture
      in terms of dividing and non-dividing cells.
AB  - The application of the exponential growth equation is the standard method
      employed in the quantitative analyses of mammalian cell proliferation in culture.
      This method is based on the implicit assumption that, within a cell population
      under study, all division events give rise to daughter cells that always divide.
      When a cell population does not adhere to this assumption, use of the exponential
      growth equation leads to errors in the determination of both population doubling
      time and cell generation time. We have derived a more general growth equation
      that defines cell growth in terms of the dividing fraction of daughter cells.
      This equation can account for population growth kinetics that derive from the
      generation of both dividing and non-dividing cells. As such, it provides a
      sensitive method for detecting non-exponential division dynamics. In addition,
      this equation can be used to determine when it is appropriate to use the standard
      exponential growth equation for the estimation of doubling time and generation
      time.

PMID- 7734624
TI  - Interleukin-3 or erythropoietin induced nuclear localization of protein kinase C
      beta isoforms in hematopoietic target cells.
AB  - Protein kinase C (PKC) has been implicated in the signal transduction pathways
      for the biological effect of both interleukin-3 (IL-3) and erythropoietin (EPO)
      in hematopoietic target cells. The goal of this study was to identify specific
      classical isoforms of PKC and their localization in hematopoietic cells in
      response to the growth factors, IL-3 or EPO. In addition to murine fetal liver
      cells as a source of normal erythroid progenitor cells, we have utilized the
      B6SUt.EP cell line, a non-transformed hematopoietic cell line that requires IL-3
      for proliferation, but for which EPO can substitute as a growth factor. With
      polyclonal antibodies prepared against peptide sequences specific for the alpha,
      beta I, beta II and gamma isoforms of PKC, we have identified beta I and beta II
      as the predominant nuclear isoforms in target cells that proliferate in response
      to IL-3 or EPO.

PMID- 7734626
TI  - An event-related potential examination of attended and unattended stimuli in
      visual selection using bilateral stimulus presentation.
AB  - The experiment reported here examined an interference paradigm using a bilateral
      stimulus presentation in which stimuli were presented simultaneously in the left
      and right visual fields. The lateralization of the early visual components
      allowed an ERP examination of material presented in each field. Attention was
      directed to one field or the other on each trial by a 100% valid cue. Two letters
      were nominated as targets and the simultaneous presentation allowed presentation
      of material compatible, incompatible or neutral with reference to the target. A
      negative peak was observed at 230 ms post stimulus at occipital and temporal
      sites. There was a variation in this peak for unattended stimuli, with compatible
      and incompatible target letters being significantly different to non-target
      letters. Contrary to previous research, this finding suggests that material is
      not filtered out at an early stage as proposed by early selection. It was found
      that the response to unattended target material also varied according to the type
      of item presented at the attended location. These findings were discussed in
      relation to previous studies which found no difference in the processing of
      unattended target and non-target material, and also in relation to suggestions
      that automatic processing of unattended material occurs only when there is
      controlled processing occurring simultaneously.

PMID- 7734625
TI  - Eysenck's personality dimensions and sex steroids in male abstinent alcoholics
      and nonalcoholics: an exploratory study.
AB  - This study investigated the relationship between alcoholics' personality
      characteristics [as indexed by the Eysenck Personality Questionnaire (EPQ)] and
      sex steroid levels. Three serum samples were drawn over a 90-min period in 58
      inpatient male alcoholics (mean 33 days sober) and 33 non-alcoholic controls. The
      EPQ was administered at approximately the same point in the treatment process.
      Replicating previous work, we found alcoholics scored significantly higher on the
      Neuroticism and Psychoticism scales of the EPQ than controls. Alcoholics also had
      higher levels of estradiol and total testosterone than controls, which may be
      reflective of a biological rebound or characteristic premorbid levels. A
      significant positive correlation was found between testosterone and extroversion
      in controls, but not in alcoholics. Alcoholics showed a positive correlation
      between estradiol and neuroticism and a negative relationship between estradiol
      and extroversion. The results suggest that (a) 'normal' hormone-personality
      relationships are disrupted in male alcoholics, and b) personality and
      psychological changes consistent with the physical feminization syndrome may
      occur in male alcoholics.

PMID- 7734627
TI  - The lateralized processing of affect in emotionally labile extraverts and
      introverts: central and autonomic effects.
AB  - The purpose of the present study was to better understand both the lateralized
      hemispheric processing of emotion and the differential neural processing of
      arousal in extraverts and introverts. We preselected right-handed male and female
      extraverts and introverts who were high in emotional lability. Each subject was
      exposed to two positive and two negative emotional stimuli under each of three
      counterbalanced conditions, including affective, cognitive, and neutral, while
      EEG and electrodermal activity (EDA) were recorded. Results showed that
      introverts are more aroused and that extraversion interacts with gender to
      produce differentiated patterns of lateralized neural activity. In addition,
      affective conditions produced higher levels of arousal than did cognitive or
      neutral conditions, particularly in the left hemisphere and under negative as
      opposed to positive stimuli. Finally, the hemispherically differentiated
      processing of positive and negative stimuli was affected by the contextual
      conditions under which they were experienced.

PMID- 7734628
TI  - Ultradian rhythms of reaction times in performance in vigilance tasks.
AB  - This study examined the presence of rhythmic fluctuations in vigilance tasks. The
      hypothesis was that individual attentional performance is subject to rhythmic
      variation beyond a linear decrease over time. In the first study the reaction
      times to an acoustic stimulus were recorded. The analysis of the individual
      periodograms indicated a rhythm in attentional capacity with periods ranging from
      5 to 30 min. These findings indicate that considerable individual variation can
      be accounted for by considering individual periodicity in performance. Although
      marked individual differences between subjects are present, the rhythmic
      fluctuations are stable within each subject and between experimental sessions.

PMID- 7734629
TI  - The cardiovascular response to postural change as a function of race.
AB  - Little is known about racial differences in cardiovascular responses to postural
      change. The immediate and delayed change from sitting to standing was studied in
      207 healthy young Asian, black, and white men and women by means of a noninvasive
      blood pressure tracking system. Whereas Asians and whites had decreased mean
      arterial pressure (MAP) 32-41 s after standing, blacks had an increase. During
      the delayed response (3 min after standing), compared to Asians and whites,
      blacks had greater increases in diastolic blood pressure and MAP. Their heart
      rate increase was also greater than Asians. For systolic blood pressure and pulse
      pressure there were Race x Family History interactions for the immediate response
      to orthostasis and Race x Gender interactions for the delayed response. Blacks
      generally displayed different cardiovascular patterns from the other two racial
      groups, possibly reflecting increased peripheral resistance and altered
      baroreceptor function.

PMID- 7734630
TI  - Elderly men and women are less responsive to startling noises: N1, P3 and blink
      evidence.
AB  - Previously we observed that the P3 component of the event-related brain potential
      (ERP) elicited by startling noises, and to a lesser extent P3 to target tones, is
      reduced in the elderly (Ford & Pfefferbaum, 1991). In the current experiment, we
      tried to eliminate possible effects of age-related hearing deficits on the
      responses to noises by filtering them to include only frequencies heard best by
      the elderly (0-1000 Hz) and by setting noise intensity relative to each subject's
      threshold (sensation level, SL). Twelve younger (mean 22 years) and 12 older
      (mean 69 years) men and women listened to three sequences of tones (80%, 500 Hz,
      70 dB SPL) and noises (20%). One type of noise occurred in each sequence (wide
      band noise set to 107 dB SPL, narrow band noise set to 107 dB SPL, or narrow band
      noise set to approximately 65 dB SL). The order of the three sequences was
      counterbalanced across age and sex. Younger subjects blinked to the noise 4-5
      times more often than older subjects and had N1 and P3 amplitudes that were 2-3
      times larger, regardless of the noise type. N1 amplitude to the background
      frequent tones and non-startle blinks did not differ between groups. Thus, even
      when noises were narrow band and set relative to each subject's threshold, older
      subjects were less responsive to startling auditory stimuli than were younger.

PMID- 7734632
TI  - Health promotion priorities of economically stressed cities.
AB  - The authors surveyed the local health officers (LHOs) of 436 northeastern and
      midwestern cities about their priorities for promoting health through prevention.
      LHOs of the most economically stressed cities identified the following as the
      five most important public health prevention goals that are amenable to
      intervention: reducing the incidence of HIV infection and AIDS, improving
      maternal and infant health, controlling sexually transmitted diseases, reducing
      violent and abusive behavior, and immunizing against infectious diseases. Their
      judgments were almost identical to those of LHOs of the least economically
      stressed cities and of a sample of African American political and public health
      leaders. LHOs of the most stressed cities were more pessimistic than their
      counterparts about achieving the objectives. The results of this survey can be
      used by federal, state, and local governments as well as private organizations as
      a guide for allocating scarce resources.

PMID- 7734631
TI  - The relation between event-related brain potential, heart rate, and blood
      pressure responses in an S1-S2 paradigm.
AB  - Event-related brain potential (ERP), heart rate (HR), and blood pressure (BP)
      responses were examined during the 6 s foreperiod of a choice-reaction task. Low
      and high trait-anxious males were required to make same/different judgements
      based on the similarity of two successively presented visual patterns. The pitch
      of a warning tone, presented at the beginning of the foreperiod, indicated
      whether speed or accuracy was to be emphasized on that trial. In different
      conditions, subjects received either a monetary reward or aversive noise,
      depending on their performance. Two clusters of parallel variations were observed
      in the foreperiod: (1) speed/accuracy instructions affected the amplitude of the
      CNV and, in interaction with anxiety group, the initial decreases in HR and
      diastolic BP; (2) type of reward, in interaction with speed/accuracy
      instructions, affected the amplitude of the P300 and PSW, the mid-interval HR
      acceleration, and subsequent increases in diastolic and systolic BP. A
      correlational analysis showed a close relationship between changes in HR and BP,
      whereas no relationship was evident between changes in ERPs and changes in HR and
      BP.

PMID- 7734633
TI  - Improved maternal and child health care access in a rural community.
AB  - Few studies have measured the extent to which expansion of health services for
      pregnant women and children in poor rural communities improves access to care and
      health status. This paper describes an underserved rural community in which
      health care initiatives increased access to comprehensive care. Over a three-year
      period, use of preventive services increased, whereas emergency room visits and
      hospitalizations at the community hospital decreased. Low birthweight, risk of
      congenital syphilis and childhood tuberculosis, and child mortality all
      decreased. Provision of comprehensive services was met with increased use of
      preventive health care and improved health outcomes in this rural community.

PMID- 7734634
TI  - To discharge or not to discharge: ethics of care for an undocumented immigrant.

PMID- 7734635
TI  - No insurance, public insurance, and private insurance: do these options
      contribute to differences in general health?
AB  - This paper examines the validity of two of the basic assumptions made about
      health care insurance and health, namely that having any insurance is associated
      with better health and, in particular, that having public, welfare-based
      insurance has better health consequences for the poor than does having no
      insurance. These questions were addressed using data from the National Medical
      Expenditure Survey, a national household-based survey in 1987 of more than 36,000
      people who were asked to report in detail about their medical care use and
      expenditures, health insurance coverage, and health and functional status. The
      results of the analysis indicate that being without insurance is associated with
      having poorer general health compared to persons with private insurance, and that
      the health of persons who qualify for public insurance is the poorest of any
      group--poorer even than those without insurance.

PMID- 7734636
TI  - Effects of reporting methods on infant mortality rate estimates for racial and
      ethnic subgroups.
AB  - Estimation of infant mortality rates for racial and ethnic subgroups has been
      plagued by uncertainties. Yet policymakers need accurate estimates to allocate
      resources toward the goal of reducing infant mortality. The authors compared
      hospital discharge records and death certificate information to birth certificate
      information from the California Birth Cohort (years 1985-1987) and 1986 Annual
      Hospital Discharge Abstract. They found discrepancies in infant mortality rates
      between reporting methods and underreporting of some non-White groups. Infant
      mortality rates based on death certificates underestimated non-White mortality,
      particularly for Native Americans and East Asians. Compared to infants who died
      soon after birth, larger discrepancies in reported race and ethnicity between
      birth certificates and death certificates for infants who died later also
      indicated possible errors in hospital reporting methods. These findings extend
      prior research that documents that standard methods of reporting infant mortality
      underestimate non-White mortality rates.

PMID- 7734637
TI  - Famous names in toxicology. Sir Ernest Kennaway.

PMID- 7734638
TI  - Use of thalidomide in leprosy.

PMID- 7734639
TI  - Myelotoxic, neurotoxic and reproductive adverse effects of nitrous oxide.
AB  - N2O is a relatively safe general anaesthetic under normal medical and dental
      anaesthetic use. It is more likely to produce megaloblastosis or neuropathy when
      used repetitively or for periods longer than 3 hours or in individuals with
      vitamin B12 deficiencies. The mechanism responsible for its myelotoxicity,
      neurotoxicity and most likely its reproductive toxicity, involves its inhibition
      of MetSyn and the resulting reduction in SAM and THF levels. Administration of
      folinic acid or methionine have been shown to protect against megaloblastosis and
      neurotoxicity occurring following N2O administration. Occupational N2O exposure
      of medical and dental personnel during its use as an analgesic is not likely to
      produce adverse reproductive outcomes except in B12-deficient individuals or in
      those routinely exposed to high N2O levels.

PMID- 7734640
TI  - Aminoglycoside toxicity and relation to dose regimen.

PMID- 7734641
TI  - Tissue reaction on PLLA versus stainless steel interlocking nails for fracture
      fixation: an animal study.
AB  - In order to develop a biodegradable interlocking nail for fracture fixation,
      polylactic acid (PLLA) rods were implanted in the femoral bone of young pigs. A
      midshaft osteotomy was performed in order to mimic a fracture. The tissue
      response to PLLA rods versus stainless steel rods was studied after 1 and 3
      months of implantation. Fracture-healing characteristics and chemical and
      mechanical properties of the PLLA rods were studied after explantation.
      Mechanical properties deteriorated during implantation and chemical properties
      changed significantly in 1 and 3 months of implantation. PLLA and stainless steel
      induced a similar tissue reaction during the studied implantation time of 3
      months.

PMID- 7734642
TI  - Leucocyte accumulation and leukotriene B4 release in response to polyglactin 910
      and expanded polytetrafluoroethylene in hollow chambers in the rat.
AB  - The acute inflammatory reaction elicited after implantation of polymer membranes
      used clinically to promote bone healing and augmentation was studied in a soft
      tissue titanium chamber model. The two materials compared were non-degradable
      expanded polytetrafluoroethylene (ePTFE) and degradable polyglactin 910, a
      copolymer of 90% polyglycolic acid and 10% polylactic acid. The membranes were
      implanted in the titanium chamber for 24 h and 6 d. The number of leucocytes
      increased for both materials, whereas the leukotriene B4 (LTB4) content decreased
      over time. In both groups polymorphonuclear granulocytes predominated. The number
      of leucocytes was significantly higher in chambers with polyglactin 910 than
      ePTFE. In contrast, the LTB4 content was higher in chambers with ePTFE than
      polyglactin 910. No differences in cell viability were observed between the
      materials tested. This study shows that both degradable and non-degradable
      polymers elicit a marked influx and activation of inflammatory cells during early
      healing in soft tissues.

PMID- 7734643
TI  - Influence of porosity on the mechanical resistance of hydroxyapatite ceramics
      under compressive stress.
AB  - Calcium phosphate ceramics are biocompatible and may develop interactions with
      human living bone tissues. They are used clinically on the surface of orthopaedic
      implants to improve primary fixation or in the form of porous blocks. Their
      brittleness is often advanced as a limitation of their common clinical use. In
      order to study the influence of porosity on the mechanical strength of calcium
      phosphate ceramics, we have tested 150 cylindrical hydroxyapatite samples with
      open porosity. The total porous volume of the ceramics has been varied from 20%
      to 60% and the pore size from 5 microns to 400 microns. The result indicates that
      not only total porosity but also pore size can influence compressive strength,
      which is in good agreement with theoretical work. After mathematical treatment of
      the results, the experiments have been modelled in the form of a polynomial
      equation which can be used to predict and optimize mechanical strength. Moreover,
      this work supports the fact that compressive strength of controlled open porosity
      implants can be comparable with that of cancellous or cortical human bone, and
      suggests that porosity should be fitted to clinical application.

PMID- 7734644
TI  - Osteogenesis in muscle with composite graft of hydroxyapatite and autogenous
      calvarial periosteum: a preliminary report.
AB  - To investigate the bone forming activity of composite grafts of hydroxyapatite
      (HA) and autogenous calvarial periosteum, porous HA rods with or without the
      periosteum were implanted into the back muscle of white rabbits. They were
      harvested 3 and 6 months after implantation and studied histologically and
      microradiographically. Bone formation in the pores of HA occurred in three out of
      four composite implants of the 3 month group, and four out of five implants of
      the 6 month group. The two specimens without bone formation revealed irregular
      calcified tissue outside the HA implant. No formation of bone and calcified
      tissue took place in any of the specimens with HA alone. These results indicate
      the potential of this new experimental system of ectopic osteogenesis and offer
      the possibility of a new improved bone graft consisting of HA and autogenous
      periosteum.

PMID- 7734645
TI  - Bone formation as a reaction to hydraulic hydroxyapatite thermal decomposition
      product used as bone cement in rabbits.
AB  - The bone activity of hydroxyapatite thermal decomposition product was evaluated
      by the amount of new bone formation after implantation into the femur of rabbits.
      New bone formation was observed to be bonded to the entire adjacent surface of
      implanted ceramics at the metaphysis in 16 out of 20 specimens 12 weeks after
      implantation.

PMID- 7734646
TI  - Urease immobilized on modified polysulphone membrane: preparation and properties.
AB  - Porous asymmetric membranes were formed by the phase inversion method from one-to
      one blends of polysulphone and its aminated derivative. Amino groups were
      introduced into polysulphone UDEL P 1700 by chlorosulphonation followed by
      amination. Urease was immobilized on the modified polysulphone membranes. The
      properties of the immobilized urease were investigated and related to the free
      enzyme. The Michaelis constant was 4.4 times higher for the immobilized than for
      the free urease. Immobilization improved the pH stability of the enzyme at pH <
      6.5 as well as its temperature stability. However, the immobilization did not
      protect the enzyme against heat inactivation at 70 degrees C; the half-times for
      the activity decay were equal to 120 and 50 min for the free and immobilized
      enzymes, respectively. The immobilized urease exhibited good storage and
      operational stability, and good reusability, properties that prove the
      applicability of the obtained system in enzymatic-membrane reactors.

PMID- 7734647
TI  - Strength retention of self-reinforced polyglycolide membrane: an experimental
      study.
AB  - Self-reinforced polyglycolide (SR-PGA) devices are stronger than non-reinforced
      ones. To study the strength retention of SR-PGA membrane, in vitro and in vivo,
      membranes were either immersed in distilled water at 37 degrees C, or implanted
      in the subcutis or around the femoral bone of rats. The SR-PGA membranes lost
      their strength in vitro by 6 wk, while they retained it for 15 wk in vivo due to
      the fibrous tissue that formed around and inside the implant (biomembrane). This
      is an advantage when clinical application of the membrane is being considered.

PMID- 7734648
TI  - Collagen bioassay by the contraction of fibroblast-populated collagen lattices.
AB  - The ability of fibroblasts to induce contraction of a collagen gel was studied
      with respect to the quantity and the quality of type I acid-soluble collagen. The
      speed of contraction and the appearance of the fibre bundles obtained after
      contraction depend not only on the ratio of the amount of collagen to fibroblasts
      but also on the process of the collagen purification. When collagen lattices made
      with a pepsinized collagen were compared to lattices made with a non-pepsinized
      collagen of the same amount, the fibres from pepsinized collagen seemed fewer
      (only 13% of the observed surface against 51% in the case of non-pepsinized
      collagen) and the lattices appeared by electron microscopy to be almost empty as
      if the lattices were comprised of less collagen. The importance of the non
      helical domain of the collagen molecule for the identification and organization
      of collagen by fibroblasts is discussed. Collagen retained by fibroblasts was
      maximum (80-99%) when collagen was prepared in the presence of protease
      inhibitors and decreased when proteolysis was not avoided, for example when
      collagen was prepared in the presence of pepsin. A test using an estimation of
      the percentage of collagen retained by fibroblasts in a contracted collagen
      lattice is proposed to check the biological quality of collagen samples.

PMID- 7734649
TI  - Development and in vitro evaluation of chitosan-based transdermal drug delivery
      systems for the controlled delivery of propranolol hydrochloride.
AB  - Membrane permeation-controlled transdermal drug delivery systems were prepared
      using the natural polymer, chitosan. An adhesive sealing technique was used to
      construct the devices. Propranolol hydrochloride was selected as the model drug
      for the present study. Chitosan membranes with different permeability to
      propranolol hydrochloride obtained by controlled cross-linking with
      glutaraldehyde were used to regulate the drug release in the devices. Chitosan
      gel was used as the drug reservoir. The ability of these devices to deliver the
      drug while supported on rabbit pinna skin was tested by conducting in vitro
      studies in modified Franz diffusion cells. The drug release profiles showed that
      the drug delivery is completely controlled by the devices. The rate of drug
      release was found to be dependent on the type of membrane used.

PMID- 7734650
TI  - Effect of adhesive layer thickness on the bond strength of a zinc polycarboxylate
      dental cement.
AB  - This study reports the effect of varying the thickness of a commercial zinc
      polycarboxylate dental cement on its adhesion in a metal-to-metal single lap
      joint. The thickness was controlled externally in a specially designed apparatus,
      rather than by the inclusion of isodimensional glass spheres, as has been done
      previously. The results show that both the tensile shear bond strength and the
      mode of failure of the cement are influenced by the thickness of the cement layer
      in the bonded joints. Hence, these results confirm previous findings that there
      is an optimum thickness for the zinc polycarboxylate layer. They also show that
      failure is more likely to be cohesive with thicker layers. The optimum thickness
      of the adhesive layer was 205 microns for the particular cement studied, PolyF
      Plus (De Trey, Dentsply, Weybridge, Surrey, UK), for which the average shear bond
      strength was found to be 4.03 MPa. Using stress analysis, the maximum shear and
      tensile stresses, tau 12(max) and sigma 11(max), have also been obtained. These
      analyses showed that joints failed at the interface between the cement layers and
      the lap joint at adhesive layer thicknesses of below 100 microns. This resulted
      from the high stress concentrations in bonded joints with thin adhesive layers.
      On the other hand, thicker joints failed cohesively within the adhesive layer
      because of greater contributions from tensile stresses in these joints.

PMID- 7734651
TI  - Response of odontoblast-like cells to hydroxyapatite ceramic granules.
AB  - In this study the inductive influence of hydroxyapatite ceramic (HAC) granules on
      preodontoblast differentiation was investigated. Dental papilla cells harvested
      from upper molar tooth germs were implanted intramuscularly in a pouch created
      for this purpose. Six months after surgery tooth-root-like bodies had developed
      with pulp-like cavities in the specimens in which dental papilla cells had been
      implanted with and without HAC. These bodies consisted of regular tubular dentine
      in the central part, fibrodentine peripherally and sometimes osteodentine. HAC
      was haphazardly enclosed in these root-like bodies, whereas the implantation of
      HAC alone had no effect.

PMID- 7734652
TI  - Electron microscopic observations on the soft tissue around clinical long-term
      percutaneous titanium implants.
AB  - Percutaneous implants of titanium ad modum Branemark have been in clinical use in
      the head and neck since 1977. The incidence of adverse reactions is low. In a
      previous study we have demonstrated the presence of inflammatory cells in the
      subcutaneous connective tissue surrounding the implants and this increased
      exposure to exogenous antigens was suggested to be compensated by a barrier of
      inflammatory cells in the soft tissue. To get further information on the nature
      of the tissue-implant contact, in the present study we have examined the
      structure of the tissue close to the percutaneous implant using transmission
      electron microscopy. We could not see evidence for an attachment of the
      epithelium to the implant, nor between the connective tissue and the implant.
      Retrieved implants were also analysed and we did not find any organized tissue
      remaining on the implants.

PMID- 7734653
TI  - Importance of ground section thickness for reliable histomorphometrical results.
AB  - Ten screw-shaped commercially pure titanium implants were inserted in 10 rabbit
      tibia. The implants with surrounding bone were harvested after 12 weeks. The
      samples were processed to be cut and ground. Histomorphometrical analyses of the
      bone-to-metal contact and the bone area around the entire implants were performed
      on transvertically cut sections at intervals, starting with 100 microns thick
      sections; then the same sections were further ground down to 50, 30 and 10
      microns. The thicker the section the more bone-to-metal contacts were
      demonstrated. A statistically significant difference was obtained when comparing
      the 100-30, 100-10, 50-30 and the 50-10 microns thick sections. Comparing the
      area measurements of 100-10, 50-30, 50-10 and 30-10 microns revealed a
      statistically significant difference. Bone-to-metal contact measurements on
      ground sections that are too thick (over 30 microns) may result in
      overestimations of the 'true' bony contacts.

PMID- 7734654
TI  - Effects of high levels of fluoride on bone formation: an in vitro model system.
AB  - In order to develop an in vitro model for the study of the effects of different
      agents on biomineralization, a three-dimensional cell culture system was
      investigated at different levels of fluoride. Rat fetal osteoblasts were seeded
      onto collagen discs and maintained in a culture medium for 40 days. Results
      showed that, at 40 days, the cultured matrices had a Ca:P ratio, mineral content
      and Fourier transform infrared (FTIR) spectrum that were close to those seen for
      normal rat bone. Viable cells, observed by light microscopy, were present in the
      matrix at 40 days. The formation of a mineralized matrix in this experimental set
      up provided a model for exploring in vitro the effects of high levels of fluoride
      on bone. The fluoride content of the mineral formed in the cultures showed a dose
      dependent increase in fluoride content with time. Also, an increase in the
      crystallinity of the apatite in the presence of fluoride, was observed by FTIR.
      The Ca:P ratio and percentage mineral by weight showed no apparent differences
      among the groups. The three-dimensional model used for this study has the
      potential to be a powerful tool in the study of time-dependent effects of drugs
      and other factors on osteoblast cell functions and subsequently on matrix
      mineralization.

PMID- 7734655
TI  - Arginine vasopressin-induced renal vasodilation mediated by nitric oxide.
AB  - The vasoconstrictor vasopressin has been reported to induce paradoxical local
      vasodilation in the basilar vasculature through stimulation of the endothelium
      derived relaxing factor nitric oxide (NO). We investigated the possibility that
      at subpressor doses, exogenous arginine vasopressin (AVP) might have a similar
      effect in the kidney. Ten Inactin-anesthetized rats were infused with sequential
      doses of AVP from 25 to 6,400 microU/min in 30-min increments. Subpressor
      infusion resulted in progressive renal vasodilation; renal blood flow (RBF)
      increased significantly going from 14 +/- 6% above basal at 200 microU/min (p <
      0.02) to 27 +/- 5% (p < 0.01) at 1,600 microU/min accompanied by a 24 +/- 5%
      decrease in renal vascular resistance (RVR). At 6,400 microU/min, blood pressure
      (BP) increased 29 +/- 6 mm Hg and RVR increased. A second group of 8 rats were
      first given 10 mg/kg b.w. of the NO synthesis inhibitor NG-nitro-L-arginine
      methyl ester (L-NAME) before infusion of AVP. L-NAME increased BP 22 +/- 3 mm Hg
      (p < 0.001), and decreased RBF 16 +/- 3% (p < 0.005). After L-NAME, no dose of
      AVP had any further effect on either BP, RBF, or RVR. Continuous infusion of a
      single subpressor dose of 100 microU AVP resulted in a 26% increase in RBF (from
      7.52 +/- 0.68 to 9.49 +/- 0.54 ml/min/g kidney weight, p < 0.001). AVP doubled
      urinary cyclic guanosine monophosphate excretion, a marker for renal NO
      synthesis, from 8.51 +/- 1.01 to 17.48 +/- 4.26 pM/min (p < 0.025).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7734656
TI  - Regionalization of endothelium-dependent relaxation in the thoracic aorta of
      pregnant and nonpregnant guinea pigs.
AB  - Regional variation in the response of the thoracic aorta to contractile agonists
      has previously been demonstrated. Since the net contractile response reflects the
      interaction between smooth muscle activation and the release of endothelial
      substances, we hypothesize that agonist-stimulated release of endothelium-derived
      nitric oxide (NO) also varies along the length of the thoracic aorta. The
      distribution of thoracic aorta estrogen receptors is also regionalized. Since
      pregnancy augments the release of endothelium-derived NO by acetylcholine (ACh)
      in some arterial beds, we further hypothesize that pregnancy enhances the
      stimulated release of NO from the thoracic aorta. Aortae were removed from
      nonpregnant and near term pregnant guinea pigs and cut into ring segments
      numbered sequentially proximal to distal. The rings were suspended at their
      optimal passive tension and submaximally contracted with prostaglandin F2 alpha.
      Endothelium-derived NO-dependent relaxation to ACh increased moving proximal to
      distal along the aorta independent of pregnancy and ACh relaxation was unaffected
      by pretreatment with physostigmine to inhibit cholinesterase. The magnitude of
      the relaxation to carbachol among the different segments was similar to ACh.
      Pregnancy decreased the ED50 for ACh of segments from the middle and distal
      segments of the thoracic aorta. Relaxation to the NO donor sodium nitroprusside
      and the nonreceptor-mediated endothelium-dependent relaxing agent A23187 was
      uniform along the length of the aorta and independent of pregnancy. These
      experiments demonstrate regional variation in the stimulated release of
      endothelium-derived NO in the guinea pig thoracic aorta which is increased by
      pregnancy.

PMID- 7734657
TI  - Effect of elastin peptides on vascular tone.
AB  - Elastin peptides are present in human blood. As elastin receptors exist on
      several cell types, especially endothelial cells, this investigation was carried
      out to study the effect of elastin peptides on vascular tone. For this purpose,
      rat aortic rings were mounted in an organ bath for isometric tension
      measurements. Elastin peptides (kappa-elastin) were added in the concentration
      range of 0.1 ng/ml to 1 microgram/ml, concentrations similar to those found in
      the circulating blood. In rat aortic rings, precontracted or not with
      noradrenaline (10(-6) M), elastin peptides induced an endothelium-dependent
      vasodilation. The pretreatment of aortic rings with N-omega-nitro-L-arginine
      methyl ester (10(-5) M), an inhibitor of nitric oxide (NO) production, or with
      indomethacin (10(-5) M), an inhibitor of cyclooxygenase, prevented elastin
      peptide-induced vasodilation. These findings suggest that elastin peptides act
      through the synthesis of prostanoids, leading to the production of NO. Moreover,
      this relaxant effect of elastin peptides was decreased or inhibited when aortic
      rings were treated with lactose (10(-5) to 10(-2) M) or laminin (10(-6) to 10(-4)
      mg/ml) whereas lactose or laminin was unable to inhibit acetylcholine-induced
      vasodilation. These findings suggest that the inhibitory effects of lactose and
      laminin are specific for elastin peptide receptors and are in agreement with
      previous studies on these receptors. As there is evidence of the degradation of
      elastin in several vascular diseases, the concept that elastin peptides may
      contribute to the control of vascular tone is discussed.

PMID- 7734658
TI  - Functional integrity of vascular allografts after endothelial removal.
AB  - Several studies have indicated that antigen-presenting endothelial cells
      represent the primary initiator of acute arterial graft rejection, leading to
      decreased arterial patency rates. Patency rates dramatically increase upon
      endothelial removal (denudation) prior to orthotopic transplantation into
      antigenically disparate hosts. Although patent, the biomechanical and functional
      changes seen in these allograft vessels (ACI rats to Lewis rats) have not been
      described. The present investigation examined functional differences between
      these allograft arteries and normal rat femoral arteries. Moreover, endothelial
      removal may also alter function; thus, an autograft injury model (Lewis to Lewis)
      was employed to discern the differences between injury and rejection. The results
      indicate that denudation injury alone caused no change in the passive stress
      strain curve, the muscle length at which stress was maximum (Lo), or in
      phenylephrine- or nitroglycerin-induced concentration-response curves. Similarly,
      concentration-response curves were not affected by allograft transplantation;
      however, both the passive stress-strain curve and Lo values were shifted to
      significantly longer lengths (0.25 and 0.20 mm, respectively), suggesting an
      increase in arterial plasticity but not compliance. Furthermore, allografts
      produced significantly weaker KCl-induced contractions than did autografts (22
      vs. 66% of control values, p < 0.05). Acetylcholine maximally relaxed
      phenylephrine-contracted arteries in the following descending order. ACI > Lewis
      > autograft > allograft. In conclusion, these data suggest that vascular
      rejection involves subendothelial tissues, is distinct from vascular injury, and
      that the denudation allograft transplantation model can be employed to examine
      this process.

PMID- 7734659
TI  - Heterogeneity of endothelial cell function for angiotensin conversion in serial
      arranged arterioles.
AB  - The involvement of the endothelial cell in the vasoconstriction induced by
      angiotensin I and II (AI, AII), and norepinephrine (NE) was studied in
      microvessels of the hamster cheek pouch before and after the following
      procedures: endothelial impairment by light-dye treatment, inhibition of
      angiotensin-converting enzyme (ACE), blockade of endothelium-derived relaxing
      factor (EDRF) and inhibiting prostaglandin (PG) synthesis. The results showed
      that in large 2nd-order arterioles, endothelial impairment did not affect the
      vasoconstrictor activity of AII and NE, nor did it alter ACE activity. However,
      in small 4th-order arterioles, endothelial impairment significantly reduced
      angiotensin conversion without altering the vasoconstrictor responses to either
      AII or NE. Thus, the endothelium plays differential roles in the modulation of
      local angiotensin conversion in these distinct segments of serial-arranged
      arterioles. Furthermore, it is unlikely that the vasoconstrictor response to AII
      in these arterioles is modulated by the endothelium through a pathway involving
      the release of EDRF or PGs.

PMID- 7734660
TI  - No role of ATP-sensitive potassium channels in the vasoconstriction produced by
      vasopressin.
AB  - The contribution of ATP-sensitive potassium channel (KATP channel) blockade in
      the vasoconstriction produced by vasopressin was studied. All experiments were
      performed using rat thoracic aorta cut in 4-mm rings, denuded from their
      endothelium and mounted into 20-ml organ baths. Glibenclamide (0.01-10 microM), a
      KATP channel antagonist, did not induce any measurable contraction, nor did it
      reduce the maximum contraction induced by vasopressin and phenylephrine. The
      specific inhibition of lemakalim-induced (a KATP channel activator) relaxation by
      vasopressin was investigated. Lemakalim (0.01-0.3 microM) relaxed both
      vasopressin (0.1 microM) and phenylephrine (0.3 microM) preconstricted vessels.
      However, in contrast to what would be expected from KATP blockade by vasopressin,
      rings preconstricted with vasopressin were more sensitive to the relaxant action
      of lemakalim, compared to phenylephrine preconstricted vessels (log[EC50] of 
      7.82 +/- 0.01 and -7.10 +/- 0.02, respectively, p < 0.05). Dose-response curves
      to papaverine (3-30 microM) in rings preconstricted with vasopressin and
      phenylephrine were comparable. When aortic rings were pretreated with lemakalim
      (0.1 microM), the maximum active tension induced by vasopressin was reduced (2.68
      +/- 0.23 in control conditions vs. 0.62 +/- 0.08 g on pretreated vessels, p <
      0.001), whereas that by phenylephrine was slightly increased. In order to explain
      the stronger relaxant action of lemakalim against vasopressin-induced
      constriction, the contribution of calcium influx through L-type calcium channels
      in the constriction of aortic rings to vasopressin and phenylephrine was
      compared.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734661
TI  - Calcitonin gene-related peptide in healthy and atheromatous human epicardial
      coronary arteries. Function and receptor characterization.
AB  - To examine the possible role of calcitonin gene-related peptide (CGRP) in the
      control of human coronary vascular tone, we have investigated the action of this
      peptide in healthy and atheromatous human epicardial coronary arteries and
      localised [125I]CGRP-binding sites in these vessels. Isolated arteries were
      obtained from 10 cardiomyopathic patients and 6 patients with ischaemic heart
      disease (IHD), who were undergoing heart transplantation. CGRP elicited
      concentration-dependent vasodilatation in preconstricted vessels. Both healthy
      and diseased coronary arteries exhibited similar maximum responses and
      sensitivity to this peptide. Removal of the endothelium did not diminish the
      vasodilator action of CGRP in non-atherosclerotic coronary arteries. [125I]CGRP
      bound to tissue sections in a concentration-dependent manner. Binding was similar
      in healthy and atheromatous vessels, with a Bmax value of 10.2 +/- 5.6 and 18.9
      +/- 3.0 amol/mg protein, and dissociation constant (Kd) of 0.07 +/- 0.1 and 0.18
      +/- 0.1 nM, respectively. Dense [125I]CGRP binding was mainly associated with
      vascular smooth muscle cells of both normal and diseased vessels with some
      patches of binding to regions of atherosclerotic plaque in vessels from patients
      with IHD. These data indicate that CGRP is a potent endothelium-independent
      vasodilator in the human coronary vasculature. The preservation of dilator
      function and CGRP receptor binding in atherosclerotic coronary arteries suggests
      that this peptide may play a role in the control or maintenance of vascular tone
      in certain disease states.

PMID- 7734662
TI  - [Treatment of chronic hepatitis C virus infection with interferon in patients
      infected with the human immunodeficiency virus].
AB  - FOUNDATION: We assessed the effectivity of the treatment with interferon (IFN) in
      patients infected by the human immunodeficiency virus (HIV) with chronic
      hepatitis (CH) by the hepatitis C virus (HCV). METHODS: We studied 14
      heterosexual males ex-parenterally drug consumers (PDC) and infected by the HIV
      (mean age 26 +/- 4.2 years), belonging to group A of CDC (1993); 10 had values of
      CD4 > 500 mmc and 4, between 200 and 500, the latter receiving treatment with
      zidovudine. In all these patients, the diagnosis of active chronic hepatitis was
      confirmed through histology. Three MUI of IFN-alpha 2b, 3 days/week during 24
      weeks were administered. Sustained response to treatment was considered as the
      normalization of the aminotransferase levels until the end of the study; partial
      response, as the 50% decrease in the initial levels until the end of the
      treatment; relapse, as the response and latter increase in 1.5 of the ALT values
      at the end of the 24 weeks; and absence of response, as the lack of significant
      changes in the aminotransferase concentrations. RESULTS: Tolerance of the
      treatment was good, without severe side effects and just in one case, the
      medication had to be interrupted. In 5 patients, there was a response (all of
      them with more than 500 CD4). In 2 of these patients, the response was partial.
      In 3, there was a relapse and 3 other patients did not show any response (CD4 >
      500). Three patients gave up the treatment. CONCLUSIONS: IFN-alpha 2b is well
      tolerated in a 24-week treatment in patients with HIV, CH and HCV. However, it
      was only effective for the control of this disease in patients with HIV infection
      with more than 500 lymphocytes CD4, without any significant effect in the
      evolution of the HIV infection.

PMID- 7734663
TI  - [Serum activity of the lactate dehydrogenase enzyme in patients with human
      immunodeficiency virus infection].
AB  - FOUNDATION: Many patients with infection by the HIV show an increase in the
      levels of the lactodehydrogenase (LCH) enzyme. In most of these cases, such
      increase has been associated to the presence of pneumonia by Pneumocystis
      carinii. In order to analyze other possible causes of this increase, we conducted
      a study in which the clinical, analytical and immunological condition of a group
      of HIV+ patients with increased levels of LDH was compared to another group whose
      values were within normal limits. MATERIAL AND METHODS: The clinical records of
      200 patients with HIV infection were retrospectively reviewed. The patients were
      divided into two groups depending if their LDH values were greater than (group A)
      or lower than (group B) the upper limit considered as normal in our laboratory
      (230-460 UI/L). Group A included 150 patients and Group B, 50. RESULTS: Both
      groups were similar with respect to age, sex risk group for HIV infection,
      hemoglobin level, platelet count and renal function. The number of patients
      fulfilling AIDS criteria was significantly greater (p < 0.05) among those with
      LDH above 460 UI/L. Leukocytes and lymphocytes CD4+ values were significantly
      greater (p < 0.05) among group B. The diseases more frequently diagnosed in group
      A were: tuberculosis in 41 cases (27%), pneumonia by P. carinii in 31 (21%),
      bacterial pneumonia in 19 (13%), disseminated disease by cytomegalovirus in 14
      (9%) and by Mycobacterium avium in 12 (8%). Among the patients with increased
      LDH, their levels were similar in the patients with tuberculosis, pneumocystosis
      and in the patients with AIDS and those which were in the first stages of the HIV
      infection. CONCLUSION: The increase in LDH among the patients with HIV infection
      in the era of the prophylaxis against P. carinii must be carefully interpreted.
      Greater levels of this enzyme are little specific, but have a high sensitivity in
      the case of tuberculosis and pneumocystosis.

PMID- 7734664
TI  - [Descriptive study of hemodialysis in the critical patient. Report of 198 cases].
AB  - In the last five year, 198 critic patients developed acute renal failure,
      requiring hemodialysis in the hospital. We realized a descriptive study and
      analyzed the factors that were statistically associated with higher mortality: a
      surgical etiology, clinic criteria for the inicial of hemodialysis, respiratory
      failure, hemodynamic inestability, hepatic insufficciency, disseminated
      intravascular coagulacion and oliguric or anuria. The sepsis and the
      cardiorrespiratory complications were the cause of mortality most important. The
      14% of the surviving requiring continue in the programs of hemodyalisis.

PMID- 7734665
TI  - [Angiotensin-converting enzyme (ACE) in sarcoidosis, tuberculosis, silicosis, and
      coal mining workers].
AB  - We studied the seric activity of the angiotensin converting enzyme (ACE) in 19
      patients with sarcoidosis, 14 tuberculosis, 16 silicosis and 15 workers of coal
      mining without silicosis and other concomitant diseases, in order to assess its
      usefulness as orientative parameter for the differential diagnosis of these
      processes. We found significantly increased values with respect to the control
      group in all of them: control group (40.84 +/- 13.06 U/l), sarcoidosis (57.77 +/-
      16.47 U/l), tuberculosis (46.85 +/- 10.25 U/l), silicosis (61.50 +/- 21.40 U/l),
      miners (71.50 +/- 12.48 U/l). We did not detect any statistically significant
      differences between the several diagnostic groups except for miners and
      tuberculosis (p = 0.04). We conclude that this parameter is hot very useful for
      the diagnostic orientation of these processes.

PMID- 7734666
TI  - [Glycogenosis type III and Crohn disease with associated ankylopoietic
      spondylitis and secondary amyloidosis. An unusual coincidence].
AB  - We present a member of a family with glycogen deposit disease (GDD) type III
      (Forbes-Cori's disease) confirmed postmortem through enzymatic analysis of the
      hepatic and muscular tissues, coinciding with a Crohn's disease associated to
      ankylopoietic spondylitis, with final development of an extended secondary
      amiloidosis, all of these diagnosis established in life of the patient and
      verified in necropsy. We comment this rare finding, the absence of similar cases
      in the bibliography and the fortuitous nature of this association given the
      impossibility to suggest another relationship.

PMID- 7734668
TI  - [Mediastinal epithelioid hemangioendothelioma].
AB  - The epitheloid hemangioendothelioma (EH) is a rare tumor of vascular origin,
      which exceptionally manifestates as a mediastinic mass. We present a new case of
      location at the upper cava vein and we review the clinical, histological and
      therapeutic characteristics of the EH.

PMID- 7734667
TI  - [Neck pyomyositis associated with polymicrobial sepsis of sinusal origin].
AB  - Spontaneous pyomyositis (primary pyomyositis) is an infrequent disease in non
      tropical countries, caused by bacterial infection of skeletal muscle. Although
      pyomyositis is associated in many cases to septicemia, the occurrence of that
      disease as a secondary manifestation of bacteremia is very unusual, requiring a
      high-grade index of suspicion to diagnose it in the early stages. We present one
      case of cervical pyomyositis, caused by Fusobacterium necrophorum and group F
      streptococcus, during the course of a sepsis of sinusal origin, that was treated
      without surgical therapy. This so uncommon form of presentation of Fusobacterium
      septicemia, its diagnosis and treatment are discussed.

PMID- 7734669
TI  - [Bilateral avascular necrosis of the femur head in an HIV-positive male].
AB  - We present a case of bilateral avascular necrosis at the hips of a HIV-positive
      male, without other predisposing antecedents. The only relevant analytic data was
      the positivity of anticardiolipin antibodies (aCL AB). We discuss the possibility
      that both in this case as in those previously described, HIV may have played a
      main role in the development of osteonecrosis.

PMID- 7734670
TI  - [Role of calcium in osteoporosis].

PMID- 7734671
TI  - [Genetic epidemiology in oncology].
AB  - Genetic Epidemiology is a discipline which studies the incidence of diseases
      among the population, trying to quantify at the same time the individual risk of
      developing them. In Oncology, it is based on the analysis of the patients
      genealogies and on the study of the polymorphisms in their DNA with specific
      markers. Its operation requires a laboratory duly equipped with the techniques of
      Molecular Biology, a section responsible of data collection regarding patients
      and relatives and another area for the computer processing of data and results.
      Its funding shall be through public agencies, but the private companies related
      with this field must be aware of the need to participate in these projects.

PMID- 7734672
TI  - [Diagnostic criteria of the task force on Lyme borreliosis].

PMID- 7734673
TI  - [Malignant pleural effusion in a cirrhotic patient].

PMID- 7734674
TI  - [Prolonged febrile syndrome as presentation form of anorectal melanoma with liver
      metastasis].

PMID- 7734675
TI  - [Bone marrow toxicity caused by ketorolac].

PMID- 7734676
TI  - [A new case of malignant fibrohistiocytoma of the breast].

PMID- 7734677
TI  - [Thrombosis of the axillary vein as initial manifestation of epidermoid carcinoma
      of the lung].

PMID- 7734678
TI  - [Multiple cholesterol embolism presenting as panarteritis nodosa].

PMID- 7734679
TI  - [Staphylococcal pyomyositis in pregnancy: a casual association?].

PMID- 7734680
TI  - [Stevens Johnson syndrome and phenytoin].

PMID- 7734681
TI  - [Myotonic dystrophy cardiopathy].

PMID- 7734682
TI  - [Home visits as part of family physician's routine].

PMID- 7734683
TI  - [Integral care of the terminal patient in primary health care].

PMID- 7734684
TI  - [Description of the development of a new model of primary care in the community
      of Valencia].
AB  - OBJECTIVE: The aim of this study was to determine to what extent the new model of
      primary care (NMPC) had been introduced and developed in the Community of
      Valencia by means of an assessment of the structure, procedures and results
      attained by the primary care teams (PCT). DESIGN: An observation study of a
      crossover type. SETTING: Primary health care. PATIENTS AND OTHER PARTICIPANTS: 70
      health centres in the Valencia Community were studied. The criteria for inclusion
      in the study were that the centre should have been open for at least two years on
      March 1st 1991 and/or had the accreditation (or had requested it) to teach family
      and community medicine. MEASUREMENTS AND MAIN RESULTS: 51 indicators were
      applied. These evaluated the seven fundamental attributes which make up the
      theoretical model: accessibility, integrated care, programmed performance,
      ongoing care, team work, community involvement and research and teaching. Of
      these seven primary care attributes, the highest valued were geographical
      accessibility and ongoing care; and those which needed to be strengthened, non
      geographical accessibility and integrated care. CONCLUSIONS: The analysis of the
      results obtained makes us reflect on the model of primary care which can be
      developed in our environment, with peoples' real needs and the resources
      available being borne in mind.

PMID- 7734686
TI  - [How much time does the physician dedicate to his patients? A study of contents
      of office visits and their length].
AB  - OBJECTIVE: To describe the content and length of General Medicine interviews at a
      health centre, analysing the problems dealt with and activities undertaken, in
      function of the time taken. DESIGN: A crossover study. SETTING: An urban health
      centre at Alcobendas (Madrid). PATIENTS AND OTHER PARTICIPANTS: The problems,
      activities and length of all the interviews (926) were recorded over a period of
      10 days. MEASUREMENTS AND MAIN RESULTS: The average length of the interviews was
      6.7 minutes (standard error SE = 0.13). More problems were dealt with, and more
      activities carried out, in the longer interviews. Problems of a psycho-social
      character and preventive activities were discussed in the long interviews.
      Significant differences were found in the length of interviews in function of the
      patient's age and between different professionals. CONCLUSION: To achieve
      integrated care which includes both preventive medicine and psycho-social
      problems, doctors must have more interview time, as these questions are not
      tackled in short interviews.

PMID- 7734685
TI  - [Drug prescriptions in general medicine practice].
AB  - OBJECTIVE: To find the origin of pharmacological prescriptions written in the
      primary care ambit, the effect of training on the prescribers and the influence
      of the organisational structure of the centres where they work on the quality of
      the drugs prescribed. DESIGN: Observational study of a crossover type. SETTING:
      Two health centres and two consulting-rooms in Areas 11 and 12, Valencia.
      MEASUREMENTS AND MAIN RESULTS: The sample calculated corresponded to 664
      prescriptions per centre. The origin of the prescription differed, depending on
      the model, so that in the consulting-rooms the origin of 55% of prescriptions was
      specialist care, whereas in the health centres this percentage went down to 31%.
      There were significant differences (p < 0.0001) in the quality of prescription in
      different organisational structures, but there were no significant differences
      among professionals with different training. CONCLUSIONS: A high percentage of
      pharmacological prescriptions have their origin in specialist care. Prescription
      quality is conditioned basically by the organisational model and is appreciably
      better in health centres.

PMID- 7734688
TI  - [Negotiations between a general practitioner and the patient after his visit to a
      private physician].
AB  - OBJECTIVE: To find what patients request from their general practitioner after
      they have seen a doctor privately and the type of negotiation which follows.
      DESIGN: A descriptive observation study of a crossover type. SETTING: Palma
      Palmilla Health Centre (Malaga); within the primary care ambit. PATIENTS AND
      OTHER PARTICIPANTS: Everyone at the on-demand clinics of five general medical
      practices, who requested something concrete from their general practitioner after
      they had seen a doctor privately, in the period from june to october 1993.
      MEASUREMENTS AND MAIN RESULTS: There were 83 patients who attended a clinic after
      seeing a doctor privately, which was 0.63% of the total consultations during this
      period. 69 of these patients asked their general practitioner to give them the
      same prescriptions that they had been prescribed privately. In 77% of the cases
      there was negotiation with the patient, a mutual promise being the most common
      result. There was no negotiation with 19 patients (23%). In 74% of the cases the
      medication prescribed privately was considered necessary. The wishes of the
      patients were fulfilled in practice in 65% of cases. CONCLUSIONS: In most cases
      there was negotiation with patients. doctors agreed to a high degree with
      patients' requests, which doctors considered sufficient and necessary for the
      diagnosis and/or treatment of their condition.

PMID- 7734687
TI  - [An epidemiological study of pulmonary tuberculosis in inpatients].
AB  - OBJECTIVE: To evaluate the profile of the patient admitted to hospital with
      pulmonary tuberculosis and the clinical-radiological signs and symptoms of the
      illness. DESIGN: A descriptive, retrospective study. SETTING: The study was
      carried out in the Miguel Servet Hospital in Zaragoza. PATIENTS AND OTHER
      PARTICIPANTS: Patients over 14 who were admitted for pulmonary tuberculosis
      between 1985 and june 1990 and who fulfilled the requisite diagnostic criteria.
      MEASUREMENTS AND MAIN RESULTS: Out of the 423 patients studied, 75.17% were male.
      Average age of the whole sample was 45.9. 31% were retired. 55% (232 cases) had
      factors predisposing to tuberculosis. The 12% were infected by HIV (human
      immunodeficiency virus). The most common presentation symptoms were coughing and
      the radiological semeiology of condensation. In 22.7% there was extrapulmonary
      tubercular infection, most commonly in ganglia. Delay in diagnosis was over three
      months in 19.8% of the cases. CONCLUSIONS: Tuberculosis is a common illness in
      our ambit and particularly affects those patients with underlying pathology.
      Given that there are still important delays in diagnosis, doctors need to be
      highly aware of the possibility.

PMID- 7734691
TI  - [Immigrants' health and primary care].

PMID- 7734690
TI  - [Prescription of exercise and physical activity to healthy persons (3).
      Cardiorespiratory resistance (and 2)].

PMID- 7734689
TI  - [Syringomas. Presentation of 7 cases].
AB  - OBJECTIVE: To further knowledge of syringoma and its importance within the
      overall condition of the patient, with a view to making it relevant in the
      differential diagnosis of other conditions such as xanthomata or milium cysts.
      DESIGN: A descriptive study of a crossover type. SETTING: Primary care and the
      dermatology clinic of a health centre in the metropolitan area of Madrid.
      PATIENTS AND OTHER PARTICIPANTS: The records of patients with syringomas
      confirmed by histological tests during 1990-1993 were examined. Patients with
      only a clinical diagnosis were discarded. The different diagnoses on referral by
      the primary care doctor were also studied. MEASUREMENTS AND MAIN RESULTS: Seven
      patients (5 women, two men) were confirmed by histological tests as suffering
      Syringomas. They were between 16 and 52 years old. Four had lesions only on the
      eyelids; in the other three they were widespread. All of them were asymptomatic,
      had been over three years without lesions and had no special previous history.
      None of them wanted to undergo treatment. The referral diagnoses cited xanthomata
      in five cases and milium cysts in the others. CONCLUSIONS: The primary care
      doctor must become better informed about syringoma, given its frequent confusion
      with other conditions (xanthomata and milium cysts). This confusion gives rise to
      unnecessary additional examinations and discomfort for the patients. These
      lesions should be verified histologically, as it is an nonaggressive method.

PMID- 7734692
TI  - [Cholestatic hepatitis associated with tenoxicam].

PMID- 7734693
TI  - [Family management of leprosy].

PMID- 7734694
TI  - [Postpartum thyroiditis. Diagnosis of 2 cases in primary care].

PMID- 7734695
TI  - [Informatics systems in teaching and practice of medicine].

PMID- 7734696
TI  - Why pathologists should take needle aspiration specimens.

PMID- 7734697
TI  - Relationship of epidermal growth factor receptor (EGFR), proliferating cell
      nuclear antigen (PCNA) and vimentin expression and various prognostic factors in
      breast cancer patients.
AB  - Cytologic specimens (FNA) from 42 primary invasive ductal breast carcinomas and
      22 matched specimens of cancer tissue were tested for EGFR status, PCNA index and
      vimentin expression by immunocytochemical staining, using an Extravidin-Biotin
      method, and their relationship with various prognostic factors was investigated.
      EGFR positivity, high PC10 score and vimentin positivity were significantly
      correlated with high histologic grade. The coordinate expression of EGFR, PCNA
      and vimentin was significantly associated with ER-negative breast carcinomas. A
      positive trend was observed between high proliferating tumours and EGFR
      expression. EGFR status and PCNA index were not correlated with axillary lymph
      node involvement, tumour size, age and menopausal status. Vimentin was
      preferentially expressed in tumours, with lymph node metastases. Co-expression of
      EGFR, PCNA and vimentin was determined in most cases. These data suggest that
      EGFR status, PCNA index and vimentin expression may be important for the
      prediction of biologically aggressive tumours.

PMID- 7734698
TI  - Transbronchial fine needle aspiration in clinical practice.
AB  - We review our experience of transbronchial fine needle aspiration (TBFNA) over a
      3-year period. A total of 112 TBFNAs were performed on 95 patients. Four
      aspirates were from peripheral lung lesions, 20 from non-ulcerated submucosal
      infiltrative lesions, 19 from mediastinal abnormalities close to the
      tracheobronchial tree, and the remaining 69 were for staging of bronchogenic
      carcinoma with apparent mediastinal lymph node spread, evaluated by chest
      computed tomography (CT). In the 20 submucosal lesions TBFNA reached a
      sensitivity of 82.3%, providing the only evidence of a malignant process in five
      cases. With respect to the 19 mediastinal lesions arising in close proximity to
      the central airways, TBFNA permitted a diagnosis in cases that would otherwise
      have required more invasive procedures, although the diagnostic sensitivity of
      the technique in this group of patients was poor (26%). In the mediastinal
      staging group, the sensitivity was 76.9%, with no false positive results.
      Complete sensitivity of TBFNA for the detection of disease was 65.8%. We conclude
      that TBFNA is a reliable and low risk procedure.

PMID- 7734699
TI  - The cytodiagnosis of meningeal involvement in familial haemophagocytic
      lymphohistiocytosis.
AB  - The cytological appearances of the cerebrospinal fluid (CSF) in two cases of
      familial haemophagocytic lymphohistiocytosis (FHL) are described. The presence of
      numerous lymphocytes and immature macrophages in the CSF, some of which showed
      lymphohistiocytosis, was indicative of meningeal involvement. The appearance of
      large numbers of immature macrophages indicated rapid deterioration and death
      within a few weeks. Furthermore, some CSF samples taken at times when the
      patients were asymptomatic contained suspicious cells, indicating asymptomatic
      persistence of the meningeal lesions. Thus, cytological examination of CSF can
      assist with the management of patients with this rare disease.

PMID- 7734700
TI  - Mucinous carcinoma of the breast co-existent with infiltrating lobular carcinoma-
      a case report.

PMID- 7734701
TI  - Myxoid neurofibroma of the male breast: fine needle aspiration cytodiagnosis.

PMID- 7734702
TI  - Chondrosarcoma of the rib presenting as a breast mass and diagnosed by fine
      needle aspiration (FNA) cytology.

PMID- 7734703
TI  - Argyrophilic nucleolar organizer regions (AgNORs) in breast lesions--a study on
      fine needle aspirates.
AB  - Nucleolar organizer region-associated proteins are argyrophilic and may be
      visualized by silver stains. This study is a prospective analysis of the AgNOR
      counts in a range of breast lesions seen in fine needle aspiration (FNA) smears.
      A total of 72 cases including ductal carcinomas (n = 24), fibrocystic change (n =
      24), fibroadenoma (n = 16), proliferative lesions (n = 4) and miscellaneous
      lesions (n = 4) were studied. The ductal carcinomas showed higher AgNOR counts
      (mean 16.63 +/- 7.09) compared with the non-malignant lesions (mean 6.39 +/-
      1.96), the difference being statistically significant. A cut off AgNOR score of
      11 could reliably discriminate malignant from non-malignant lesions. In ductal
      carcinomas, the AgNOR scores showed a tendency to increase with higher grades of
      malignancy. There was no correlation with the presence or absence of lymph node
      metastases at the time of presentation. It is concluded that AgNOR counting,
      although tedious, is inexpensive, and provides useful information regarding
      cellular proliferation, and can supplement information obtained by more
      sophisticated techniques.

PMID- 7734705
TI  - Partial rescreening.

PMID- 7734704
TI  - Oncocytic carcinoma of the parotid gland: a problem in fine needle aspiration
      diagnosis.

PMID- 7734706
TI  - [Peptic ulcer in patients with cirrhosis].
AB  - This study was carried out at the of gastroenterology service from Hospital
      Nacional "Daniel A. Carrion" Callao-Peru, between June 1993 and May 1994, in
      order to determine the incidence, as well as, the clinical and endoscopic
      features of peptic ulcer disease in cirrhotic patients. 24 out of 46 (52.17%)
      hospitalized cirrhotic patient during this period, had peptic ulcer disease. The
      male:female ratio was 1:1. The mean age was 63.54 years, ranging from 44 to 90.
      There was statistical association (p < 0.05) between the severity of liver
      disease determined by Child Pugh Score and the presence of gastric ulcer.
      Regarding symptomatology, 54.16% had hematemesis and/or melena and 37.5% were
      asymptomatic. 6 patients had 2 or more ulcers, presenting the total series as a
      whole 35 ulcers, whose size ranged from 0.4 a 1.2 cm. Gastric antrum was the most
      often location (60%) followed by duodenal bulb (20%). We conclude that peptic
      ulcer disease in our cirrhotic patients is more frequent than reported by
      international literature (5-32%). Severity of liver disease was associated to
      gastric ulcer.

PMID- 7734707
TI  - [Colorectal polyps in a hospital of Metropolitan Lima].
AB  - A prospective study concerning colorectal polyps in symptomatic patients was held
      at Lima, Peru, an area considered of low incidence for colorectal neoplasia. In
      137 patients, 272 polyps were resected by colonoscopic polypectomy or surgery.
      55.9% were adenomas, 40.4% non neoplastic polyps and 3.7% polypoid carcinomas.
      The distribution of polyps, and the incidence of dysplasia and malignant changes
      in the adenomas, were similar of that reported in areas with high incidence of
      colorectal cancer. A high proportion of patients with adenomas (21.4% had a
      synchronous advanced carcinoma, specially if there were multiple adenomas. The
      figure was lower in patients with only non neoplastic polyps (7.5%). There were
      no cases of "de novo" carcinoma. This evidence suggest that adenomas play an
      essential role in colorectal cancer histogenesis, even in areas of low incidence
      of this neoplasia.

PMID- 7734708
TI  - [Neonatal cholestasis in the Children's Health Institute: evaluation of
      obstructive cholangiopathy syndrome in children].
AB  - In order to establish a clinical or laboratory difference 52 Clinical charts of
      patients that were attended at the Gastroenterologic Unit at the Children's
      Hospital in Lima-Peru since January 1988 to December 1992, with the diagnosis of
      Neonatal Cholestasis were reviewed. 14 of them were discharged; at the end we
      have reviewed 23 cases of biliary atresia, 8 of neonatal hepatitis and 7 with
      congenital choledochal cyst. All patients went through sonography, scintigraphy
      and liver biopsy. No statistical differences were found in symptomatology, as
      well as jaundice, feces color or coluria. We concluded that the most accurate way
      to predict a diagnosis is through the sonography, scintigraphy and liver biopsy.

PMID- 7734709
TI  - [Study of intestinal microflora in children with acute and persistent diarrhea].
AB  - The etiology and pathogenesis of persistent diarrhoea is usually multifactorial
      and sometimes can not be identified. It is necessary to define if an alteration
      of the enteric microflora is a risk factor that influence the duration of the
      diarrhoea. 30 infants with acute diarrhoea and 30 with persistent diarrhoea were
      studied. A sample of duodenal content was taken by a double-lumen tube and
      processed microbiologically in search for enteric microorganisms, anaerobic and
      Candida. These results were correlated with the nutritional status, the previous
      use of Metronidazole and the results of the stool culture. The presence of
      bacterial overgrowth and the identification of the duodenal microflora is an
      important factor for the persistence of the diarrhoea. There was a quantitative
      and qualitative alteration of the duodenal flora in both groups of patients.

PMID- 7734710
TI  - [Gastric cancer in the Honorio Delgado Regional Hospital in Arequipa].
AB  - We present the study of 120 cases of gastric carcinoma, observed in the Hospital
      Regional Honorio Delgado from Arequipa Peru, in 2683 gastroscopies, with 4.5% of
      incidence. We offer date of age, sex, race, occupation, antecedents, social
      economic conditions, clinics, diagnosis, pathologies aspects and mortality.

PMID- 7734711
TI  - [Intra-abdominal sepsis: surgical management].
AB  - Intraabdominal sepsis is a frequent clinical disorder in inpatients with severe
      consequences as septic shock and multisystem organic failure. It starts with the
      presence of germs or toxins from the abdominal cavity either intra or
      retroperitoneal. Pathophysiology is not yet totally understood. Clinical
      diagnosis many times is difficult and image aids are important. Treatment is
      based in the administration of antibiotics, nutritional support, ventilatory and
      hemodynamic aids. The keystone of the management is surgery. This review details
      the main technics and strategies of the surgeon in the operative room.

PMID- 7734712
TI  - [Complication of typhoid fever in children: anasarca. A case report and review of
      the literature].
AB  - We report a case of a nine year-old boy with typhoid fever and complications,
      including generalized edema, which is not named in the pertinent literature. We
      discuss finding in this patient.

PMID- 7734713
TI  - [Kuhn's paradigms and Helicobacter pylori: disencounters].

PMID- 7734714
TI  - Class switch recombination of the immunoglobulin heavy chain gene frequently
      occurs in B-cell lymphomas associated with rearrangement of the BCL2 gene.
AB  - B-cell lymphomas, mainly follicular lymphomas, carrying a t(14;18) chromosomal
      translocation associated with rearrangement of the BCL2 gene and the
      immunoglobulin heavy chain (IGH) gene, share many similarities with germinal
      center B cells in the secondary lymphoid follicle. In the germinal center,
      antigen-stimulated B cells proliferate and differentiate while undergoing isotype
      class switching of their immunoglobulin heavy chains. To examine whether BCL2
      positive lymphoma cells show class switch recombination similar to that in the
      germinal center B cells, we studied the genomic configurations of the IGH gene
      loci in 38 patients with B-cell lymphomas. Sixteen (80%) out of 20 patients with
      BCL2-positive lymphomas showed class switch recombination on translocated and/or
      productive IGH gene loci. Lymphoma cells from 7 of the 16 patients expressed the
      gamma-heavy chain on their surfaces, indicating functional class switching to the
      gamma-constant gene on the productive allele. By contrast, 6 (33%) of the 18
      patients lacking the BCL2 rearrangements exhibited class switch recombination.
      Statistical analysis revealed that the BCL2-positive lymphomas underwent switch
      recombination on either allele at a significantly higher frequency than the BCL2
      negative lymphomas (P = 0.0099). This indicates that follicular lymphoma, not
      only morphologically but also functionally, recapitulates the germinal center. We
      propose that the up-regulated BCL2 expression itself is capable of playing an
      important role in immunoglobulin class switching.

PMID- 7734715
TI  - CD33+ B-cell precursor acute lymphoblastic leukemia in children: a distinct
      subgroup of B-cell precursor acute lymphoblastic leukemia.
AB  - Clinical and laboratory features associated with CD33 expression were analysed in
      123 children with B-precursor acute lymphoblastic leukemia (ALL), including 85 at
      onset, 34 at relapse and four in a refractory state to induction therapy. CD33
      was demonstrated in 13 patients (15.3%) at onset, and it was associated with
      coexpression of T-cell and multipotential hematopoietic cell-associated antigens,
      i.e. CD2, CD4 and CD7, which were observed in four of 11 analysed patients (P <
      0.01). Patients with CD33 expression were older than those without CD33 (P <
      0.01). Although CD33 was the strongest predictor of a poor outcome (event-free
      survival, 44% for CD33+ and 75% for CD33-patients; P = 0.0041) in univariate
      analysis, multivariate analysis did not demonstrate significance (P = 0.0645).
      Fourteen of 38 patients (36.8%) at relapse or in a refractory state showed CD33
      expression. Analysis of CD33 expression had also been performed at onset in 16 of
      these patients and showed acquisition of CD33 in six of 13 patients who had been
      negative for this antigen at onset. Thus, it seems that CD33+ B-precursor ALL is
      derived from undifferentiated cells minimally committed to B-cell lineage and
      more homogeneous than so-called My+ B-precursor ALL with regard to the clinical
      and biological features. The frequent expression of CD33 on the cells which
      acquired resistance to chemotherapy may have resulted from expansion of a CD33+
      original minor clone or clonal evolution.

PMID- 7734716
TI  - Improved treatment results of non-Hodgkin's lymphoma in children: a report from
      the Children's Cancer and Leukemia Study Group of Japan.
AB  - From 1985 to 1989, 69 patients with non-Hodgkin's lymphoma (NHL) were treated by
      members of the Children's Cancer and Leukemia Study Group of Japan with a
      protocol consisting of vincristine, prednisolone, cyclophosphamide, doxorubicin,
      high-dose methotrexate (HD-MTX), mercaptopurine and cytarabine; central nervous
      system (CNS) prophylaxis with intrathecal MTX and hydrocortisone (NHL855). The 4
      year event-free survival (EFS) was 78% (S.E., 10%) for patients with localized
      disease (n = 18) and 38% (S.E., 7%) for those with advanced disease (n = 51).
      Among the patients with advanced disease, those with non-lymphoblastic lymphoma
      tended to have a better 4-year EFS than those with lymphoblastic lymphoma (52%
      vs. 25%). Based on these findings, we initiated a new protocol NHL890 in which
      patients were assigned to two different chemotherapies according to the
      histology. Non-lymphoblastic subtype was treated almost identically to NHL855
      while asparaginase and VP-16 were newly added in the consolidation-maintenance
      phase in advanced-stage lymphoblastic lymphoma. Sixty-seven patients with
      advanced disease were assessable. The overall 4-year EFS for advanced disease
      improved to 69% (S.E., 6%). A significant improvement was gained in the
      lymphoblastic lymphoma with a 4-year EFS of 56% (S.E., 11%) as compared with 25%
      (S.E., 9%) in the preceding study (P < 0.05). These findings suggest the
      importance of histology in the treatment of advanced-stage non-Hodgkin's lymphoma
      in childhood.

PMID- 7734717
TI  - Cerebral mass lesions associated with adult T-cell leukemia/lymphoma.
AB  - Three patients with adult T-cell leukemia/lymphoma (ATLL) accompanied by cerebral
      mass lesions in their courses are reported. The findings of cerebrospinal fluid
      and their history suggested that those three cerebral involvements were the mass
      lesions derived from ATLL. Two of the three patients had acute type and the other
      one had chronic type ATLL. During the same period in which these three patients
      were observed, we experienced 17 other patients with ATLL. Although this group
      included 12 lymphoma type and five acute type ATLL, involvement of the central
      nervous system (CNS) was not observed in these 17 patients. The incidence of CNS
      involvement was 3/20 (15%). The prognoses of the three patients after the
      occurrence of CNS involvement was 1, 4, and 8 months, respectively. In these
      three patients, cerebral lesions became the cause of death for two patients
      although they continued to be in complete remission hematologically. Cerebral
      lesions, once occurring, are very hard to cure and spoil the quality of life for
      sufferers. From these points, prophylactic therapy against central nervous system
      involvement seems necessary not only for acute leukemias, but also for ATLL
      patients.

PMID- 7734718
TI  - Gay men should not be forgotten.

PMID- 7734719
TI  - The use of unconventional remedies among HIV-positive men living in California.
AB  - This study compared use of unconventional remedies in two groups of HIV-positive
      men (N = 63). Employing a multiple-choice questionnaire, the authors assessed the
      use of and attitudes toward unconventional remedies among two groups of white HIV
      positive men similar in age, socioeconomic status, and severity of illness, all
      of whom lived in Northern California. One group (n = 36) participated in AIDS
      clinical trial protocols; the other group (n = 27) received health care at a
      community health center. Participants at all sites expressed positive views upon
      increasing unconventional remedies. Individuals enrolled in the clinical trial
      protocols for investigational drugs used unconventional remedies significantly
      less than the community health center participants, who were enrolled in an open
      clinical trial of hypericin, an unproven remedy.

PMID- 7734720
TI  - Comprehensive care and the sanatoria: Cuba's response to HIV/AIDS.
AB  - The authors present an overview of Cuba's response to HIV/AIDS including: (a) the
      development of comprehensive health care in Cuba; (b) the epidemiology of AIDS in
      Cuba; (c) the sanatoria approach to treatment and recent changes; (d) the idea of
      comprehensive HIV/AIDS care as a basic human right; (e) the effects of the
      special period on the HIV/AIDS program and containment of the epidemic; and (f) a
      critique of Cuba's HIV/AIDS program.

PMID- 7734721
TI  - Changes in taste associated with intravenous administration of pentamidine.
AB  - In this pilot study the authors set out to: (a) describe the incidence of taste
      changes associated with intravenous (i.v.) pentamidine treatment; and (b)
      determine the factors that are related to making the taste changes better and
      worse. A convenience sample (N = 18) of adult male outpatients with AIDS
      participated in this study. One hundred percent of the participants experienced
      an unpleasant taste after the administration of pentamidine. The largest
      percentage of patients had a metallic taste (89%, n = 16); while 67% (n = 12)
      experienced a bitter taste. These data suggest that healthcare providers need to
      assess for the unpleasant taste associated with i.v. pentamidine and develop
      appropriate management strategies.

PMID- 7734722
TI  - Nursing education and the HIV/AIDS pandemic.

PMID- 7734723
TI  - Let's push for HBO therapy.

PMID- 7734724
TI  - Not only for nurses.

PMID- 7734725
TI  - Confidentially speaking.

PMID- 7734727
TI  - Sex- and age-related changes in the biophysical properties of cuticular lipids of
      the housefly, Musca domestica.
AB  - We examined the biophysical properties of cuticular lipids isolated from the
      housefly, Musca domestica. Melting temperatures (Tm) of surface lipids isolated
      from female houseflies decreased from 39.3 degrees C to 35.3 degrees C as the
      females attained sexual maturity and produced sex pheromone, whereas those
      prepared from males did not change with age. Lipids melted over a 10-25 degrees C
      temperature range, and their physical properties were a complex function of the
      properties of the component lipids. The Tm of total cuticular lipids was slightly
      below that of cuticular hydrocarbons (HC), the predominant lipid fraction.
      Hydrocarbons were further fractionated into saturated, unsaturated, and methyl
      branched components. The order of decreasing Tm was total alkanes > total HCs >
      methyl-branched alkanes > alkenes. For 1-day-old flies, measured TmS of
      hydrocarbons were 1.3-5.5 degrees C lower than TmS calculated from a weighted
      average of TmS for saturated and unsaturated components. For 4-day-old flies,
      calculated TmS underestimated Tm by 11-14 degrees C.

PMID- 7734726
TI  - Differential effects of neuropeptides on the distal and mid-tubules of the house
      cricket.
AB  - In the Malpighian tubules of Acheta, the distal and middle segments are
      functionally and morphologically quite distinct (Spring and Kim, Mol Comp Physiol
      12:130-145, 1993). Furthermore, they respond quite differently to corpora
      cardiaca (CC) homogenates, dibutyryl cAMP, and A23187 (Kim and Spring, J Insect
      Physiol 38:373-381, 1992). In this study we compared secretion by these two
      regions in response to Acheta and Romalea CC extracts, synthetic Manduca sexta
      diuretic peptide (Mas-DP1), and the family of synthetic myotropic peptides, the
      achetakinins, isolated from Acheta. Both Acheta and Romalea CC extracts had
      opposite effects on the two regions: mid-tubule secretion increased 3-fold
      whereas secretion by the distal segment declined 75-80%. Mas-DP1 increased
      secretion by the mid-tubule more than 3-fold and had no effect on the distal
      segment. All of the achetakinins decreased secretion by the distal tubule, with
      achetakinin 1 being least effective (55% inhibition) and achetakinin 5 being most
      effective (75% inhibition). Achetakinins 1 and 2 increased mid-tubule secretion
      by 3.7- and 3.3-fold, respectively, whereas the others had no effect on this
      region. Regarding HPLC fractions of CC extracts, in general the more hydrophilic
      fractions inhibited secretion by both distal and mid-tubules. The more
      hydrophobic fractions were nearly uniformly stimulatory when applied to the mid
      tubule, and either inhibited secretion or had no effect on the distal region. The
      possible interpretations of these data and the implications towards future
      research are discussed.

PMID- 7734728
TI  - XXX National meeting of the Italian Society of Gastroenterology, XI meeting of
      the Italian Association of Hospital Gastroenterologists, V meeting of the Italian
      Society of Coloproctology. Firenze, 3-7 December 1994. Abstracts.

PMID- 7734729
TI  - Three-dimensional gradients of voltage during development of the nervous system
      as invisible coordinates for the establishment of embryonic pattern.
AB  - We are interested in the generation of endogenous electric fields associated with
      ionic currents driven through the vertebrate embryo by the transepithelial
      potential of its surface ectoderm. Using a non-invasive vibrating electrode for
      the measurement of ionic current, we have provided measurements of currents
      traversing amphibian embryos, and a preliminary report of the internal,
      extracellular voltage gradient under the neural plate which polarizes the embryo
      in the rostral/caudal axis (Metcalf et al. [1994] J. Exp. Zool. 268:307-322).
      Here we complete a description of this gradient in electrical potential (ca. 10
      mV/mm, caudally negative), describe a simultaneous gradient organized in the
      medial/lateral axis (ca. 5-18 mV/mm, negative at the margins of the neural
      folds), and describe their appearance and disappearance during ontogeny of the
      axolotl embryo. Both voltage gradients are not expressed until neurulation, and
      disappear at its climax. This appearance and disappearance correlates with the
      shunting of current out of the lateral margins of the neural folds in rostral
      regions of the embryo beginning at stage 15, and is not associated with a more
      substantial current leak from the blastopore which appears at gastrulation. A
      steady blastopore current is still present after neural tube formation when intra
      embryonic electric fields have been extinguished. We discuss the direct
      experimental tests supporting the hypothesis that these extracellular electric
      fields both polarize the early vertebrate embryo and serve as cues for
      morphogenesis and pattern.

PMID- 7734730
TI  - Developmental expression of fibroblast growth factor receptor-1 (cek-1; flg)
      during heart development.
AB  - Previous work in this laboratory has indicated that fibroblast growth factor-2
      (FGF-2; bFGF) regulates the initial stages of avian heart development in
      paracrine and autocrine fashion (Parlow et al. [1991] Dev. Biol. 146:139-147;
      Sugi et al. [1993] Dev. Biol. 157:28-37). Because these findings inferred the
      presence of a functional receptor for fibroblast growth factor (FGFR), we have
      immunochemically assessed the appearance of FGFR-1 (cek-1; flg) during
      development. Using a peptide-generated antibody, Western blots of total embryonic
      proteins revealed that FGFR-1 was barely detectable at pre-heart stages, followed
      by sequential increases in relative abundance that peaked at stage 24, followed
      by a decline at days 7-14. Western blots of proteins from isolated embryonic
      hearts demonstrated a similar developmental pattern, except that FGFR-1
      expression was not decreased at later stages. The presence of FGFR-1 mRNA was
      verified by reverse transcription/polymerase chain reaction (RT/PCR)
      amplification. Immunohistochemical examination revealed punctate deposits of FGFR
      1 in the precardiac endoderm at stage 6, followed by detection in the endoderm,
      foregut, and pre-cardiac splanchnic mesoderm at stage 8 and in the newly formed
      myocardium at the heart tube stage (9/10). By stage 13, FGFR-1 staining was
      observed only in the myocardium, a pattern which persisted at least until stage
      30 (day 7), after which only isolated hearts were examined. After stage 30,
      staining was diminished in the ventricle, but not in the atrium. Staining of
      cardiac endothelial cells was not observed at any stage. A functional role for
      FGFR-1 was indicated by experiments in which anti-FGFR-1, but not pre-absorbed
      antiserum, retarded proliferation and multilayering of cardiogenic cells in an in
      vitro model of cardiac morphogenesis.

PMID- 7734731
TI  - Myotube driven myogenic recruitment of cells during in vitro myogenesis.
AB  - Muscular dysgenesis (mdg) is a recessive lethal mutation in the mouse which
      drastically affects skeletal muscle development during embryonic life.
      Physiologically, the disease is characterized by a complete paralysis resulting
      from a lack of excitation-contraction coupling. Existing electrophysiological,
      biochemical, and genetic evidence shows that mdg/mdg mice express a basic
      alteration of L-type voltage-sensitive Ca2+ channels in skeletal muscle. Studies
      on mdg/mdg myotubes in primary culture have shown that +/+ fibroblasts or +/+
      Schwann cells may fuse with them and correct their functional deficiency by
      genetic complementation. As the spontaneous formation of heterocaryons is thought
      to be an exclusive property of myoblasts, we asked whether fibroblasts may have
      changed their properties before fusion occurred. We used primary cells issued
      from sciatic nerves dissected from newborn transgenic mice carrying the pHuDes1
      nls-LacZ transgene (Des-LacZ cells) as non-muscle cells. These cells were mainly
      fibroblasts (80%) positive for Thy1.1 and Schwann cells positive for S100. The
      cultures were negative for myogenic markers (desmin, troponin T), did not form
      myotubes long-term, and did not display significant activation of the muscle
      reporter gene (pHuDes1-nls-LacZ). After a few days in coculture with dysgenic or
      normal myotubes, the muscle reporter gene (beta-galactosidase) was detected both
      within dysgenic myotubes, correlating with the restoration of normal contractile
      activity, and normal myotubes. As well as confirming that fusion takes place,
      this shows that Des-LacZ cells nuclei incorporated into recipient myotubes
      express their own myogenic genes. Moreover, individual mononucleated Des-LacZ
      cells expressing beta-galactosidase were observed, indicating that myogenic genes
      were being expressed before fusion. This suggests a mechanism of myotube driven
      myogenic recruitment of cells during the in vitro myogenesis. Analysis of the
      distribution of the induced Des-LacZ cells (positive for beta-galactosidase) in
      compartmentalized muscle cocultures showed that in the presence of dysgenic
      myotubes, these cells were equally distributed in both myotube free and enriched
      areas, whereas in the presence of normal myotubes, the positive cells remained in
      close vicinity of the myotubes. This difference could be explained by the fact
      that the dysgenic phenotype might include release of the induction process from
      its normal controls. Our results are consistent with the idea of a transcellular
      mechanism triggering myogenic differentiation in non-muscle cells, and that
      myotubes themselves are able to drive myogenic recruitment of cells during the in
      vitro myogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734732
TI  - Mesenchymal stem cells reside within the connective tissues of many organs.
AB  - Previous studies have noted the presence of mesenchymal stem cells located within
      the connective tissue matrices of avian skeletal muscle, dermis, and heart. In
      these studies, clonal analysis coupled with dexamethasone treatment revealed the
      presence of multiple populations of stem cells composed of both lineage-committed
      progenitor mesenchymal stem cells and lineage-uncommitted pluripotent mesenchymal
      stem cells. The present study was undertaken to assess the distribution of these
      stem cells in the connective tissues throughout various regions of the body. Day
      11 chick embryos were divided into 26 separate regions. Heart, limb skeletal
      muscle, and limb dermis were included as control tissues. Cells were harvested
      enzymatically and grown using conditions optimal for the isolation,
      cryopreservation, and propagation of avian mesenchymal stem cells. Cell aliquots
      were plated, incubated with various concentrations of dexamethasone, and examined
      for differentiated phenotypes. Four recurring phenotypes appeared in
      dexamethasone-treated stem cells: skeletal muscle myotubes, fat cells, cartilage
      nodules, and bone nodules. These results suggest that progenitor mesenchymal stem
      cells and putative pluripotent mesenchymal stem cells with the potential to form
      at least four tissues of mesodermal origin have a widespread distribution
      throughout the body, being located within the connective tissue compartments of
      many organs and organ systems.

PMID- 7734733
TI  - Examination of fibronectin distribution and its sources in the regenerating newt
      limb by immunocytochemistry and in situ hybridization.
AB  - Using monoclonal antibodies (mAbs) reactive to newt limb regenerates, we hope to
      gain insight into the identity and function of regeneration significant
      molecules. mAb MT4 (matrix 4) identifies an extracellular matrix (ECM) protein
      that is strongly up-regulated first in the distal stump and then in the blastema
      during regeneration. Within the first 24 hr after amputation the MT4 antigen is
      localized to an acellular space beneath the wound epithelium, and first appears
      in the basal cells of the wound epithelium between days 5 and 7. At mid-bud
      blastema stages, the MT4 antigen is homogeneously distributed as thin fibers in
      the blastema ECM, and is later largely restricted to the distal tip of the
      blastema and the areas of cartilage condensation. After extraction and
      immunoblotting, the MT4 antigen was observed as three reduced species of M(r)
      225, 250, and 260. Taken together, the immunoblot and immunocytochemistry results
      suggested that mAb MT4 recognized newt fibronectin (FN). Sequence from a cDNA
      (NvFN.10) obtained by screening a newt blastema cDNA expression library with mAb
      MT4 conclusively identified the MT4 antigen as FN. To further investigate the
      expression of FN in regeneration, cDNA NvFN.10 was used to construct a riboprobe
      and in situ hybridization was done. In the unamputated limb only a few scattered
      cells expressed the FN gene. Within the first 3 days after amputation strong
      hybridization signal was observed in the basal cells of the wound epithelium.
      Most of the stump cells that dedifferentiated and accumulated beneath the wound
      epithelium at 7 days expressed the FN gene, while the basal cells of the wound
      epithelium maintained their expression. At mid- and late-bud blastema stages the
      vast majority of the blastema cells were strongly expressing the FN gene, but the
      wound epithelial cells now showed only weak FN transcription. Thus initially FN
      comes from the plasma. Then FN is synthesized by both the wound epithelium and
      mesenchyme. Finally, at blastema stages FN is produced primarily by the
      mesenchyme. The expression pattern of FN throughout regeneration suggests that
      this glycoprotein has roles in wound epithelial and mesenchymal cell migration
      and mesenchymal cell proliferation and differentiation.

PMID- 7734734
TI  - Mouse multidrug resistance 1a/3 gene is the earliest known endothelial cell
      differentiation marker during blood-brain barrier development.
AB  - Molecular mechanisms of endothelial cell differentiation during blood-brain
      barrier (BBB) development is not well understood due to the lack of specific
      molecular markers. Here we describe that expression of the mouse multidrug
      resistance 1a/3 (mdr1a/3) gene can be detected specifically in subsets of
      vascular endothelial cells associated with neural tissues at as early as
      embryonic day 10.5 (E10.5). This onset of mdr1a/3 gene expression coincides with
      the previously described first appearance of morphologically distinct endothelial
      cells in neural tissues during BBB development. To our knowledge, the mdr1a/3
      gene is the earliest endothelial cell differentiation marker gene during BBB
      development described thus far. In addition, we have found that neither the level
      nor pattern of mdr1a/3 gene expression in BBB endothelial cells is affected by
      aberrant cortical neuronal layers in mutant mouse reeler.

PMID- 7734735
TI  - Blood vessel formation in the avian limb bud involves angioblastic and
      angiotrophic growth.
AB  - The vasculature of the avian limb bud takes its origin from the intersomitic
      vessels as can be shown by ink perfusion of the embryo. While the primitive
      vessels form a central network in the early limb bud, an area of about 100
      microns in width from the ectoderm inward remains free from lumenized vessels.
      However, this subectodermal avascular zone contains isolated angioblasts, which
      can be demonstrated by confocal laser scanning microscopy in connection with QH-1
      staining. QH-1-positive cells from the avascular zone are capable of giving rise
      to endothelial cells when grafted ectopically into a "permissive" environment
      such as the dorso-lateral paraxial mesoderm. Several grafting sites are compared
      regarding their permissiveness for capillary formation. In order to investigate
      the origin of the QH-1-positive angioblasts we carried out injections of DiI-Ac
      LDL, which is specifically taken up by endothelial cells and macrophages, and
      found the lumenized vessels and a few isolated cells in the peripheral limb
      mesoderm stained. In double-labelling studies combining DiI-Ac-LDL and QH-1, it
      can be shown that there exists a pool of isolated angioblasts that are only QH-1
      positive, but have not incorporated DiI-Ac-LDL. In contrast to the lumenized
      vessels in the core of the limb bud, we found that angioblasts in the avascular
      zone do not proliferate, as shown by proliferation studies applying the BrdU
      method to semithin sections in connection with QH-1-labelled parallel sections.
      We conclude that the vascularization of the avian limb bud is achieved by a
      combination of angiotrophic growth (sprouting of vessels) and angioblastic growth
      (recruitment of angioblasts from the limb mesoderm.

PMID- 7734736
TI  - Experimental analysis of Msx-1 and Msx-2 gene expression during chick mandibular
      morphogenesis.
AB  - Homeobox-containing genes are thought to be involved in regulating pattern
      formation in a variety of tissues during embryogenesis. We have examined the
      expression of the homeobox-related genes Msx-1 and Msx-2 during the development
      of the chick mandibular arch. Northern blot hybridization indicates that
      transcripts for both Msx-1 (1.6 Kb) and Msx-2 (3 Kb) are present in the
      mandibular arch as early as stage 18. The levels of both transcripts in the whole
      mandible decrease as cartilage is formed in vivo and in vitro. Using in situ
      hybridization, transcripts of Msx-1 were localized in high amounts to the
      mesenchyme of the mesial tips of the arches. Msx-2 transcripts were localized in
      high amounts to medial regions of the arches. Little or no hybridization of
      either probe was detected in the chondrogenic and myogenic regions of the arches.
      Transcripts of both genes were also excluded from calcified bone and cartilage.
      Our results further demonstrate that the mesial tip mesenchyme expressing Msx-1
      includes areas of highly proliferative cells and has in vitro chondrogenic
      potential. The region of mesenchymal cells expressing the Msx-2 gene overlap with
      areas of developmentally programmed cell death which also contain very few
      proliferative cells and lack chondrogenic potential in vitro. These results are
      consistent with the possibility that Msx-1 may be involved in the outgrowth of
      the mandibular arch and Msx-2 may be involved in both developmentally programmed
      cell death and delineating the non-chondrogenic region of the medial part of the
      mandibular arch.

PMID- 7734737
TI  - Proteinuria and progressive renal disease. 2nd international symposium. Vienna,
      July 2, 1994. Abstracts.

PMID- 7734738
TI  - Introduction: nature of microalbuminuria, proteinuria, and progressive renal
      disease.

PMID- 7734739
TI  - Epilogue: summary of several new guidelines on renoprotective treatment
      strategies to delay progression of renal disease in diabetic patients.

PMID- 7734740
TI  - Are there any glycemic thresholds for the serious microvascular diabetic
      complications?
AB  - We randomized 102 patients with insulin-dependent diabetes to intensified
      treatment (n = 48 at baseline, n = 42 after 7.5 years) or standard treatment (n =
      54 at baseline, n = 47 after 7.5 years). As has previously been reported,
      intensified treatment resulted in a retardation of retinopathy, nephropathy, and
      neuropathy. For the purpose of the present study, all patients were analyzed, and
      the complications related to the mean glycosylated hemoglobin (HbA1c) level.
      Patients with mild retinopathy at onset did not develop serious retinopathy,
      visual deterioration, or manifest nephropathy if their mean HbA1c during 7.5
      years was below 7% (normal range, 3.9%-5.7%). Neuropathy only rarely developed in
      patients with HbA1c below 7%. Visual acuity in the patient group with more
      advanced retinopathy at baseline was also better preserved if the patient had
      lower HbA1c; also whereas these patients needed photocoagulation treatment just
      as often as the patients with higher HbA1c because of proliferative retinopathy
      or sight-threatening macular edema. The risk for the development of serious and
      disabling microvascular complications seems to be small in patients with insulin
      dependent diabetes mellitus if they start intensified treatment when they have
      mild retinopathy, and achieve mean HbA1c levels below 7% (1.2 times the upper
      normal limit).

PMID- 7734741
TI  - Effects of fructose on D-[6-3H]-glucose uptake and sorbitol metabolism of bovine
      retina in vitro.
AB  - In order to study the influence of fructose on sorbitol formation, bovine retinal
      tissue was incubated with different concentrations of glucose and fructose, and
      supplemented with tracer amounts of D-[6-3H]-glucose. Combining high-performance
      liquid chromatography (HPLC) with radioactivity determinations allowed detection
      of sorbitol and fructose derived from glucose in the incubation medium. In
      addition, the total amount of sorbitol was measured with a sensitive
      bioluminescence method. In this way, it was possible to distinguish between
      sorbitol formation from glucose and fructose. High concentrations of glucose in
      the medium increased the formation of sorbitol and fructose from glucose.
      Addition of fructose to the incubation medium diminished the sorbitol and
      fructose formation from glucose although the total amount of sorbitol increased
      significantly. Incubating retinal tissue with an aldose reductase inhibitor
      decreased sorbitol formation from glucose but did not influence the formation of
      sorbitol from fructose. Thus, the present findings clearly demonstrate the
      important influence exerted by fructose on sorbitol formation. The possible
      significance of the present finding is discussed with respect to diabetes
      retinopathy and retinal osmoregulation.

PMID- 7734742
TI  - A study of thyroid function and prevalence of thyroid autoantibodies in an
      African diabetic population.
AB  - It is generally believed that autoimmune disorders are uncommon in Africans. Some
      workers have argued that insulin-dependent diabetes mellitus (IDDM) is rare in
      Africa on account of this reduced proneness to autoimmunity. However, it is
      undetermined whether or not Africans with IDDM have increased prevalence of
      thyroid dysfunction and autoimmunity, two phenomena strongly associated with
      Caucasian IDDM. We determined thyroid function and the prevalence of thyroid
      autoimmunity in IDDM Africans. The results are compared with those of a
      nondiabetic group and a group with non-insulin-dependent diabetes mellitus
      (NIDDM). Thyroid hormone levels were significantly lower in IDDM patients than in
      the control population and the NIDDM population. Subclinical hypothyroidism was
      present in 21% of the 28 IDDM patients. One patient was hypothyroid and another
      hyperthyroid. Of the 60 NIDDM patients, 5 (8.3%) had subclinical hypothyroidism.
      Forty-six percent of the IDDM patients had significant levels of serum thyroid
      autoantibodies (TAAB). This was significantly higher than the 1.4% and 1.7%,
      respectively, in the controls and NIDDMs. Presence of TAAB in the patients was
      strongly associated with thyroid dysfunction, female preponderance, and duration
      of diabetes mellitus. Thyroid dysfunction and autoimmunity are common in
      Nigerians clinically diagnosed as IDDM, and have prevalence rates comparable to
      other populations but higher than rates previously reported from some other
      African groups. The increased prevalence of thyroid autoimmunity in the IDDM
      supports the view that these patients are true IDDMs rather than variants of
      NIDDM or malnutrition-related diabetes mellitus (MRDM) as has been suggested by
      some workers.

PMID- 7734743
TI  - Significance of high levels of serum IgA and IgA-class circulating immune
      complexes (IgA-CIC) in patients with non-insulin-dependent diabetes mellitus.
AB  - Significance of serum IgA and IgA-class circulating immune complexes (IgA-CIC)
      elevation in patients with non-insulin-dependent diabetes mellitus (NIDDM) was
      described. Seventeen patients with NIDDM and 17 patients with diffuse mesangial
      proliferative glomerulonephritis without deposition of IgA (DPGN) as controls
      were examined. The levels of serum IgA in patients with NIDDM were significantly
      higher than those in patients with DPGN (p < or = 0.01). The levels of IgA-CIC in
      patients with NIDDM were also significantly higher than those in patients with
      DPGN (p < or = 0.01). Production of IgA derived from B cells and the proportion
      of IgA bearing B cells in patients with NIDDM were not significantly higher than
      those in patients with DPGN. Furthermore, the levels of IgA in pharyngeal
      washings from diabetic patients were not significantly higher than those for DPGN
      patients. Duration of diabetes, the level of HbA1c, and the presence of
      hypertension, microalbuminuria, or retinopathy showed no significant correlations
      with the levels of serum IgA or IgA-CIC in patients with NIDDM. It was postulated
      that the elevations of serum IgA and IgA-CIC were based on subclinical infection
      of the mucosa and/or deterioration of IgA clearance in patients with NIDDM.

PMID- 7734744
TI  - Ophthalmic referral rates for patients with diabetes in primary-care clinics
      located in disadvantaged urban communities.
AB  - The level of adherence with recommended standards for ophthalmic examinations was
      assessed in a purposive sample of diabetic patient charts (n = 350) from four
      clinics in medically underserved areas. All of the clinics referred patients with
      diabetes to off-site services for comprehensive eye examinations (dilation,
      visual acuity, and intraocular pressure); adherence with the standard of care was
      defined as a chart note indicating a referral for an ophthalmic examination.
      Overall, 86% of the patients were from high-risk minority groups (black or
      Hispanic) for diabetes and its complications. Mean age and duration of diabetes
      were 57.7 and 8.8 years, respectively. Referrals for ophthalmic exams were noted
      in 18% of the charts during the year preceding the review and in 28.6% of the
      charts during the 2 preceding years. Annual referrals in the preceding 2 years
      were noted in 3.1% of the charts. Eye disease was noted as a diagnosis in 22%.
      Patients who had a diagnosis of eye disease noted in their charts had a 7.5-fold
      increase in the odds of having a referral noted. The increased likelihood of
      being referred in patients with known eye disease may be due to follow-up of
      current eye problems.

PMID- 7734745
TI  - Type II diabetic nephropathy in perspective.
AB  - The magnitude of type II diabetic nephropathy dilemma is observable in the
      growing number of diabetic patients with end-stage renal lesion receiving various
      modalities of treatment. Progressive glomerulopathy associated with proteinuria
      and hypertension is strongly causative of renal failure and mortality in diabetic
      patients. Besides hypertension, diabetes exceeds all other glomerulopathies in
      causing end-stage renal failure. Alterations in glomerular structure and function
      observed in diabetic patients are implicated in the development and progression
      of renal derangement. Diabetic glomerulosclerosis, an aggregate of structural and
      functional perturbations of the kidney, is indicated by alterations in the
      accumulation of extracellular matrix components, The pathology, epidemiology,
      risk factors, and other dependent variables may throw some light in the
      pathogenetic mechanisms and the prevention, treatment, and management modalities
      of type II diabetic nephropathy.

PMID- 7734746
TI  - Genetic modification of seed proteins.
AB  - Knowledge concerning the genetic modification of seed proteins to improve their
      nutritional quality has advanced significantly over the past two years. Research
      in this area has focused almost exclusively on model systems, rather than on
      agronomically important plants. The extent to which genetic engineering of seed
      protein genes will improve crop seed nutritional quality remains to be
      determined.

PMID- 7734747
TI  - Nuclear magnetic resonance analysis of cell metabolism.
AB  - Nuclear magnetic resonance (NMR) continues to be a useful tool for the study of
      cellular metabolism. A variety of NMR techniques have been developed or newly
      applied to the analysis of cell systems. Many of these techniques are
      particularly useful for the analysis of immobilized cell bioreactors. The use of
      several NMR techniques has been an integral part of recent comprehensive
      metabolic studies. Novel computer-based models and methods have been developed
      which may make NMR study of metabolism more accessible and powerful.

PMID- 7734748
TI  - Implications and applications of apoptosis in cell culture.
AB  - Numerous stimuli, including viral infection and deprivation of cell growth
      factors, can induce apoptosis (programmed cell death) of cells grown in culture.
      The genetic machinery that controls the apoptotic response is currently being
      investigated. The expression of genes involved in this process using recombinant
      DNA technology has been utilized to control and limit programmed cell death in
      cultured cells. In the future, this technology may be used to increase the
      productive lifetime of cell culture systems.

PMID- 7734749
TI  - Disulfide bond formation and eukaryotic secretory productivity.
AB  - The relationship between disulfide bond formation and the exit of proteins from
      the endoplasmic reticulum may prove critical to maximizing the productivity of
      eukaryotic expression systems. During the past year, manipulation of redox active
      foldase enzymes, global inhibition of disulfide formation with dithiothreitol,
      and removal of specific disulfides via site-directed mutagenesis have all been
      shown to result in surprising effects on the rate and efficiency of protein
      secretion in eukaryotic hosts.

PMID- 7734750
TI  - Large-scale oligoribonucleotide production.
AB  - Growing interest in RNAs for biomedical, agricultural, and other applications has
      necessitated the development of methods for producing oligoribonucleotides in
      milligram, or larger, quantities. Recent research on in vitro transcription has
      focused on optimizing solution conditions and the use of immobilized templates.
      In the alternative area of organic chemical synthesis, significant effort has
      been channeled into improving coupling efficiencies and producing modified RNA
      analogs which retain activity but have higher stability than unmodified RNAs.

PMID- 7734751
TI  - Neuroengineering in biological and biosynthetic systems.
AB  - Recent advances in restoring neural function to biological systems and
      incorporating neural function into bioartificial devices have been made possible
      by developments in biology, materials science, engineering, and physics. Further
      progress is being achieved in relating cellular function to overall system
      behavior through the application of quantitative experimental and theoretical
      techniques.

PMID- 7734753
TI  - Plant biotechnology.

PMID- 7734752
TI  - Validation of biotechnology products and processes.
AB  - Recent advances in the validation of biotechnology products have focused on
      clearer definitions of the requirements for cleaning validation, especially for
      multi-product facilities. In addition, sensitive analytical methods have been
      developed that can be validated. This, together with computer validation, has
      contributed to the biotechnology industry's ability to demonstrate the production
      of safe and efficacious products for biotherapeutic and diagnostic purposes.

PMID- 7734754
TI  - Biochemical engineering.

PMID- 7734755
TI  - Cardiovascular disease mortality in RI, 1986-1991.

PMID- 7734756
TI  - Cardiovascular disease risk factors and preventive practices in Rhode Island,
      1988 and 1992.

PMID- 7734757
TI  - The Pawtucket Heart Health Program: progress in promoting health.

PMID- 7734758
TI  - The hidden effects of antihypertensive and lipid-lowering agents on the
      prevention and regression of atherogenesis: new management strategies.

PMID- 7734759
TI  - The physician's challenge in tobacco control.

PMID- 7734760
TI  - Increasing physical activity: the issues.

PMID- 7734761
TI  - Nutrition for the 1990s: planning to prevent chronic disease.

PMID- 7734762
TI  - Cardiovascular health in RI: an approach for the '90s.

PMID- 7734763
TI  - Screening for high blood cholesterol among RI adults.

PMID- 7734764
TI  - The tobacco vending machine: an idea whose time has passed.

PMID- 7734765
TI  - European Society of Mastology. Consensus Conference on Breast Cancer Screening.
      Paris, 4-5 February, 1993. Report of the Evaluation Committee.

PMID- 7734766
TI  - [Soft tissue sarcomas: general review].
AB  - Soft tissues sarcomas are an heterogeneous group of neoplasms. Their epidemiology
      is still poorly known. Great strides have been made in the genetic study over the
      last few years. Histologic grade, tumor size and deep location are the main
      independent prognostic factors in multivariate analysis using the Cox model.
      Overall 5-year survival is approximately 50% in most of the studies. Surgical
      conservative treatment associated with radiotherapy is actually preferred to
      radical surgery, because no survival difference is found between the two
      treatments. Radiation therapy modalities are discussed: preoperative,
      postoperative irradiation, interstitial brachytherapy. Doxorubicin, ifosfamide
      and DTIC are the most efficient drugs. However, response rates obtained with
      polychemotherapy are still less than 50%. High-dose chemotherapy is an
      encouraging concept. Edatrexate and Taxotere show interesting response rates in
      phase II clinical trials. Adjuvant chemotherapy efficiency is probably low: a
      meta-analysis shows a 5-year survival increase of 9%. Neoadjuvant chemotherapy
      allows a high rate of conservative treatment.

PMID- 7734767
TI  - [Discovery of a new gene frequently inactivated in human cancers: protein p16, a
      cell cycle regulator].
AB  - Comprehension of cell cycle regulation mechanisms progressed very quickly the
      past few years. The last discovery concern a known gene, MTS1 (Multiple Tumor
      suppressor), encoding a protein of M(r) 16K, intrinsic component of the cell
      cycle machinery. p16 protein inhibits an enzyme called CDK4 (cyclin-dependent
      kinase 4) which is a kinase implicated in the control of cell proliferation
      between the G1 and S phases. Now, a team reported that MTS1 gene is frequently
      inactivated in a wide variety of human cancers. This important finding will
      provide a new link between cell cycle control and oncogenesis, if MTS1 is proved
      to be a classic tumor suppressor gene.

PMID- 7734768
TI  - [Comparison of relative survival vs. classical survival. Apropos of primary
      bronchial cancer].
AB  - The aim of the study is to compare the usefulness of a recent relative survival
      model versus more classical methods for univariate and multivariate survival
      analysis, applied to a population of patients with surgically cured non small
      cell lung cancer, in determination of prognostic factors and appreciation of the
      exact role of age on survival. We studied 156 patients surgically treated between
      1975 and 1988. Both univariate and multivariate analysis were performed, using
      the actuarial method and the Cox model for crude survival and the additive
      Hakulinen model (1985) for relative survival (total risk of death equal to
      natural risk of death in general population plus disease specific risk of death)
      which is an age-adjusted survival corrected for normal life expectancy. In
      addition, the loss in life expectancy was also calculated. Our 156 patients
      (including six females), whose age ranged from 30 to 78 (mean age 59) were almost
      all current or former smokers (97%) and 63% had clinical trouble. Squamous cell
      carcinoma was the most common histology (76%) before adenocarcinomas (20%).
      Pneumonectomy and lobectomy were equally performed. Post surgical TNM staging was
      stage I = 78 (50.3%), II = 23 (14.8%), IIIa = 44 (28.4%), IIIb = 10 (6.5%). By 31
      December 1990, 116 patients had died, 24 were alive and 16 lost to follow-up. In
      univariate analysis, overall survival is (crude/relative): 1 year (75.8%/77.5%),
      2 years (53.8%/56.0%), 5 years (28.7%/32.5%), 10 years (14.4%/18.9%). Univariate
      prognostic factors are histopathology, surgical procedure and post operative TNM
      staging. The overall loss in life expectancy is 71.4% (5.5 years of life
      expectancy vs 19.21). The loss is higher for the younger patients than for the
      older ones (73% for the 30-49 year old group--59.2% for the more than 70 year old
      group). In multivariate analysis, prognostic factors are: Cox model: post
      surgical TNM staging, histopathology and age (RR = 2.18 [1.13-4.23] for patients
      over 65); Hakulinen model: TNM staging. In this model, age is no longer a
      significant prognostic factor. In conclusion, 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 is the post-surgical TNM staging. The
      relative survival model of Hakulinen dismissed age as a significant prognostic
      factor.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7734769
TI  - [Lymphoid depletion type 4 Hodgkin disease. Anatomoclinical review of 35 cases].
AB  - The pathological material of 35 patients with Hodgkin's disease lymphocyte
      depletion type (type 4) is reviewed with an immunohistochemistry study on
      paraffin-embedded sections. The new pathologic data are compared with clinical
      features. These 35 patients are 4.7% of 742 previously untreated patients managed
      in this institution from 1960 to 1991. The diagnosis of 31 of the 35 patients was
      rectified, 17 to non-Hodgkin's lymphoma (12 unclassifiable and five anaplastic Ki
      1 positive) and 14 to another type of Hodgkin's disease (six nodular sclerosis
      and eight mixed cellularity). In four cases, the pathologic material was neither
      sufficient nor satisfactory to allow a clear-cut distinction between Hodgkin's
      disease and non-Hodgkin's lymphoma. The analysis of clinical data before and
      after pathological revision did not show any difference in clinical features,
      either between Hodgkin's disease "type 4" and other types (1, 2 or 3) or between
      cases with Hodgkin's disease and those with non-Hodgkin's lymphoma. There is,
      however, a significant male predominance for Hodgkin's disease versus non
      Hodgkin's lymphoma (P = 0.029, exact Fisher test), and B symptoms in non
      Hodgkin's lymphomas (P = 0.056), whereas B symptoms are commonly seen in advanced
      stages of Hodgkin's disease. It is emphasized that all Hodgkin's disease of
      lymphocyte-depletion type should be reviewed and discussed before any treatment,
      and this diagnosis actually means non-Hodgkin's lymphoma or other types of
      Hodgkin's disease.

PMID- 7734770
TI  - [Value of mono-antibiotic therapy using piperacillin associated with sulbactam
      and possibly followed by vancomycin in febrile neutropenia in solid tumors].
AB  - We evaluated the efficacy and safety of a monotherapy by piperacillin and
      sulbactam potentially associated to vancomycin as an empiric antimicrobial
      therapy in febrile neutropenic patients treated with nephrotoxic chemotherapy for
      solid tumors. Twenty-three patients were treated during 32 episodes with
      piperacillin 4 g i.v. every 8 hours and sulbactam 1 g IV every 8 hours. If the
      patient remained febrile after 48 hours, 1 g of vancomycin i.v. was added every
      12 hours as indicated by our study design. The mean duration of neutropenia was
      5.5 days (2-13 days). In ten episodes, the granulocyte nadir was < 100/mm3.
      Infection was microbiologically documented in seven episodes (22%) with six Gram
      negative bacilli and 3 Gram positive cocci. There were 19 apyrexia with
      piperacillin and sulbactam (59%) and further seven were resolved by the addition
      of vancomycin (total success: 81%). Failure was observed in six episodes
      consecutive to germ resistance (one episode), clinical deterioration (one
      episode), relapsing fever related to Pseudomonas infection (one episode),
      persistent fever despite withdrawal of neutropenia and no microbiological
      documentation (two episodes) and protocol violation (one episode). Neither septic
      death nor toxicity were observed. We conclude that this empirical treatment is
      active and safe in short period febrile neutropenic episodes in patients heavily
      treated with nephrotoxic chemotherapy for solid tumors.

PMID- 7734771
TI  - [Oncogenic activation of p21(ras) and pp60(c-src) in human colonic Caco-2 cells
      decreases insulin receptor function and expression through protein kinase C
      dependent and independent pathways].
AB  - In view of the potent mitogenic effect exerted by insulin in human colonic cells,
      we used Caco-2 cells transfected with an activated (Val12) human Ha-ras gene or
      the polyoma middle T (PyMT) oncogene, a constitutive activator of pp60c-src
      tyrosine kinase activity, to investigate the effect of oncogenic p21ras and
      PyMT/pp60c-src on insulin mitogenic signaling. As compared to vector control Caco
      2 cells, both oncogene-transfected cells exhibited: 1) a lost of response to
      insulin's stimulatory effect on mitogen-activated protein (MAP) kinase activity
      and cell proliferation, both of which were constitutively increased; 2) a
      decrease in insulin receptor (IR) affinity and insulin-stimulated exogenous
      tyrosine kinase activity, which resulted, at least in part, from increased
      protein kinase C (PKC) activity (4), since both IR alterations were partially
      corrected by PKC down-regulation; and 3) a decrease in both insulin receptor mRNA
      level and insulin receptor number, which was independent of PKC since it
      persisted after PKC down-regulation. In conclusion, oncogenic p21ras and
      PyMT/pp60c-src abolished insulin mitogenic signaling in Caco-2 cells through
      mechanisms involving (i) constitutive activation of MAP kinase, and (ii) marked
      decreases in both insulin receptor function and expression which were mediated by
      PKC-dependent and PKC-independent pathways respectively. This is the first
      evidence that, when oncogenically activated, p21ras and pp60c-src not only exert
      a negative control on insulin receptor function but also repress insulin receptor
      gene expression in human colonic cells.

PMID- 7734772
TI  - [Difference between the effects of S9788, verapamil and quinine on the reversion
      of multidrug resistance in two human tumor cell lines].

PMID- 7734773
TI  - [Characterization of the mechanism of cross-resistance to vinca alkaloids and
      taxoids in the human J82 bladder tumor cell line].
AB  - A phenotype of resistance to the new vinca alkaloid Navelbine was induced in the
      J82 human bladder carcinoma cells. The resistance factor of the resistant cell
      line (J82-NVB) to Navelbine was 17. The resistance phenotype of these cells is
      not a multidrug-resistance (MDR) phenotype. J82-NVB cells lack overexpression of
      P-glycoprotein and cross-resistance to MDR drugs like doxorubicin,
      epipodophyllotoxins or colchicine. Navelbine efflux was similar in sensitive and
      resistant cells, and resistance could not be explained by a difference of drug
      accumulation in these two cell lines. The cells were cross-resistant to vinca
      alkaloids and taxoids whose targets are microtubules. Immunofluorescence study of
      microtubules showed that depolymerization occured for the same Navelbine
      concentration in sensitive and resistant cells. This concentration induced growth
      inhibition in sensitive but not in resistant cells. Moreover, depolymerization
      induced by Navelbine treatment was reversible, after drug removal, in resistant
      cells only. This study suggests that J82-NVB cell resistance mechanism involves
      alterations of microtubule dynamics, allowing recovery of microtubules functions
      after treatment.

PMID- 7734774
TI  - [Modulation of adriamycin cytotoxicity on K 562 and K562adri cells by interferon
      alpha and/or all-trans-retinoic acid].
AB  - Multidrug Resistant (MDR) plays a major role in chemoresistance. Alpha Interferon
      (IFN) and all trans retinoic acid (ATRA) have antiproliferative effect and IFN
      regulates several genes, some of them implicated in the regulation of MDR gene
      expression. We have studied the modulations of adriamycin cytotoxicity by IFN
      and/or ATRA on K 562 (MDR-) and resistant to adriamycin K 562 adri (MDR+) cell
      lines. We observed an important increase of adriamycin cytotoxicity on both K 562
      and K 562 adri by low dose of IFN and ATRA. Studies of MDR gene expression shows
      an increase in K 562 adri after exposure to IFN or ATRA. So the observed effect
      is not due to a down regulation of MDR gene expression but probably to the own
      antiproliferative effect of IFN and ATRA in combination with the cytotoxicity of
      adriamycin.

PMID- 7734775
TI  - [Repertory of T lymphocytes in patients with stage A chronic lymphoid leukemia:
      revealed by monoclonal expansion of T cells in vivo].

PMID- 7734777
TI  - [Acquisition of resistance to suramin in the cells of fibrosarcoma in Chinese
      hamsters accompanied by morphologic modification and increased metastatic
      capacity].

PMID- 7734776
TI  - [Effect of the association of antimitotic agents on cell lines of human
      adenocarcinoma].

PMID- 7734778
TI  - [Effect of the modality of exposure on the action of S9788 on the modulation of
      multidrug resistance of human tumor cell lines].

PMID- 7734779
TI  - Future of Nutrition for the Low-Birth-Weight Infant. Proceedings of a symposium.
      Saint Julien en Beaujolais, France, 23-25 August 1993.

PMID- 7734780
TI  - Development of human intestinal and gastric enzymes.
AB  - In humans as opposed to rodents development of the gastrointestinal tract is much
      less coordinated with functional changes occurring at different times during the
      fetal period. This article reviews developmental patterns of intestinal brush
      border enzymes, lysosomal enzymes, peroxisomal enzymes and de novo synthesis of
      intestinal lipoproteins. It also describes the developmental patterns of gastric
      lipase and pepsin during early fetal life. Data are presented on the most recent
      observations related to the regulatory mechanisms in the development of human
      intestinal brush border hydrolases. A clearer understanding of the ontogeny and
      of the regulatory mechanism of the functional development of the gastrointestinal
      tract will enable researchers and clinicians to improve nutritional support in a
      fashion appropriate for the digestive and metabolic capabilities of an infant at
      any developmental stage.

PMID- 7734781
TI  - Vitamin D: metabolism, and effects on growth and development.

PMID- 7734782
TI  - Calcium, phosphorus and magnesium needs for the low-birth-weight infant.
AB  - Parental mineral-containing solutions for LBW infants should be started soon
      after birth. For the initiation of parenteral nutrition and during short-term
      therapy for less than 2 weeks' duration, LBW infants should receive parenteral
      nutrition solutions at rates of approximately 120-130 ml/kg/day, containing
      minerals at the following concentrations: Ca 15 mM, P 15 mM and Mg 2.5 mM. For
      optimal growth and nutrient utilization, however, LBW infants maintained on
      parenteral nutrition at rates of 120-130 ml/kg/day for 2 or more weeks should
      receive mineral concentrations of Ca 20 mM, P 20 mM and Mg 2.5 mM. In addition,
      these latter mixtures must contain amino acids in concentrations greater than or
      equal to 2.2 g% and cysteine-HCl must be provided. As newer formulations emerge,
      these recommendations may be modified. For human milk-fed LBW infants, after 1
      week of enteral feeding, Ca and P should be supplied as fortifiers. Ca 2-3
      mmol/kg/day and P 1.5-2.0 mmol/kg/day should be provided in addition to human
      milk. Magnesium supplementation of human milk is unnecessary. These
      recommendations assume that the intake of human milk is approximately 200
      ml/kg/day and will decrease as more bioavailable mineral salts are found. For LBW
      infants fed commercial formula, the intake of Ca should be greater than 3.5
      mmol/kg/day, P 2.5 mmol/kg/day and Mg 0.2 mmol/kg/day. These recommendations
      assume reported bioavailabilities of mineral salts. If more bioavailable sources
      are found, these recommendations will decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734784
TI  - Influence of early diet on outcome in preterm infants.
AB  - Despite intensive research in infant nutrition over the past 50 years,
      uncertainty exists in nearly every major area of practice. A key factor in this
      uncertainty has been the lack of knowledge on whether diet or nutritional status
      in early life has a long-term or permanent influence on health, growth or
      performance. The possibility that early nutrition has long-term consequences in
      man has been much debated. There have been limited opportunities to perform
      formal randomized studies on the effect of early nutrition in humans and many
      studies have been flawed by problems with study design. Infants born preterm are
      a special group. At the start of our study in 1982, evidence on which to base
      choice of diet was inconsistent and related only to short-term outcome, and diets
      available for such babies differed greatly in nutrient content. In this group it
      was both ethical and practical to conduct a formal, randomized trial of early
      diet and outcome and the results were clearly needed for management decisions. We
      have undertaken a long-term prospective outcome study on 926 preterm infants
      randomly assigned to the diet received in the neonatal period. Surviving children
      have been followed at 9 months, 18 months and now 7.5-8 years of age. Our
      findings suggest that human milk may contain factors which promote brain growth
      or development and also bone mineralization later in childhood. Outcome data from
      the randomized trials show that a very brief period of dietary manipulation (on
      average for the first 4 weeks of life) influences later development.

PMID- 7734783
TI  - Mineral balance and whole body bone mineral content in very low-birth-weight
      infants.
AB  - Fat and mineral metabolic balance studies were performed in 25 normal very low
      birth-weight infants (< or = 1500 g at birth) fed either pooled pasteurized human
      milk supplemented with calcium, phosphorus and magnesium, or a preterm formula.
      Calcium, phosphorus and magnesium intake were similar in both groups and averaged
      100 mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus
      retention was higher in the subjects fed fortified human milk than in those
      receiving a preterm formula (65 +/- 14 and 62 +/- 9 mg/kg/day versus 55 +/- 12
      and 47 +/- 7 mg/kg/day respectively). The difference was only significant for
      phosphorus. Magnesium retention was similar in the two groups and averaged 3
      mg/kg/day. Fat intake and absorption was significantly higher in the preterm
      formula fed group than in the one fed fortified human milk (5.5 +/- 0.4 g/kg/day
      and 88 +/- 4% versus 4.2 +/- 1 g/kg/day, 79 +/- 6% respectively). Assessment of
      the whole body bone mineral content by dual energy X-ray absorptiometry was
      performed at 3 and 6 months of age in another group of 25 low-birth-weight
      infants fed either fortified human milk or a preterm formula. Whole body bone
      mineral content (BMCt) was low (43.3 +/- 30.8 g of hydroxyapatite) at 3 months of
      age (theoretical term) compared to normal full-term newborns at birth. There was
      no significant influence of the diet. At 6 months of age, BMCt reached 168.6 +/-
      36.6 g, a value similar to that of full-term newborns, with no significant
      difference between the two regimen groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734786
TI  - Calcium, phosphorus, magnesium and the placenta.

PMID- 7734785
TI  - Placental supply of energy and protein substrates to the fetus.
AB  - Table 1 shows an approximate metabolic balance sheet for the fetal sheep at late
      gestation. The metabolic balance in humans has not been determined but is
      estimated to be similar, except for a greater caloric requirement for fat
      deposition, adding about 33 kcal/kg/day to the total fetal caloric intake (34).
      The total fetal metabolic rate accounts for about 58% of caloric uptake. This
      percentage is close to the sum of the measured oxidation percentages of the
      principal energy substrates; this discrepancy cannot yet be explained.

PMID- 7734787
TI  - Diet and body composition of preterm infants.
AB  - There have been few systematic studies of the effects of energy and protein
      intake on the body composition of preterm infants. Analysis of published studies
      suggests a roughly inverse relation between energy stored per gram of weight gain
      (a measure of the fatness of new tissues) and the ratio of protein to energy in
      the preterm infant's diet. At least within a certain range of energy and protein
      intakes, a higher protein diet promotes leaner body composition. Studies of the
      effects of varying the dietary ratio of carbohydrate to fat in preterm infants
      have shown reduced rates of carbon dioxide production with high-fat diets, fed by
      either the parenteral or enteral route. The little information available suggests
      no clear effect of varying the carbohydrate-to-fat ratio on body composition. The
      mineral content of the body can be influenced by diet. Insufficient intakes of
      calcium and phosphorus reduce the bone mineral content and thus the whole-body
      content of these minerals.

PMID- 7734788
TI  - Food and microbiological problems in the newborn: data and practice.
AB  - We have reviewed the relationships of food, nutrition and feeding practices to
      various infections in the newborn. Tentative conclusions are made: (a) the
      initial use of human milk (raw or pasteurized) continues to offer advantages in
      the care of babies in intensive care; (b) attempts to mimic the microbiological
      effects of breast milk by manipulation of the composition of infant formulas have
      so far achieved little success, but this is a rapidly developing field; (c) we
      are wary of the widespread use of breast milk "fortifiers" until there is
      evidence that they do not adversely affect the protective properties of breast
      milk; (d) the doubtful advantages of nasojejunal feeding need to be weighed
      against the increased bacterial contamination of the upper small bowel; (e)
      systems monitoring in milk kitchens and the handling of feeds in the neonatal
      unit are an integral part of comprehensive neonatal care; (f) to limit nosocomial
      infection, particular attention to the faecal-food-oral route is necessary since
      there is potential for multiplication of initial contamination of food.

PMID- 7734790
TI  - Sodium, potassium and chloride needs in low-birth-weight infants.
AB  - A review of the daily requirements of sodium, potassium and chloride in preterm
      infants with particular emphasis on very low-birth-weight (VLBW) infants is given
      against the background of our present knowledge of the homeostatic regulation of
      these electrolytes during early postnatal life. Particular attention has been
      given to the importance of balanced fluid and electrolyte homeostasis in the
      control of compartment volumes and tonicity. The risk of rapid changes of
      extracellular fluid osmolality for many organs, and particularly for the brain,
      has been stressed. In order to obtain an adequate sodium and fluid balance during
      the first postnatal weeks in preterm infants of varying gestational age,
      recommendations for sodium intake during the first 4-5 postnatal weeks are given.

PMID- 7734789
TI  - Water, energy and early postnatal growth in preterm infants.
AB  - Non-invasive methods, including stable isotope techniques, indirect calorimetry,
      nutritional balance and skinfold thickness, have given a new insight into early
      postnatal growth in neonates. Neonates and premature infants in particular,
      create an unusual opportunity to study the fluid and metabolic adaptation to
      extrauterine life because their physical environment can be controlled, fluid and
      energy balance can be measured and the link between metabolism and the energetics
      of their postnatal growth can be assessed accurately. Thus the postnatal time
      course of total body water, heat production, energy cost of growth and
      composition of weight gain have been quantified in a series of "healthy" low
      birth-weight premature infants. These results show that total body water is
      remarkably stable between postnatal days 3-21. Energy expenditure and heat
      production rates increase postnatally from mean values of 40 kcal/kg/day during
      the first week to 60 kcal/kg/day in the third week. An apparent energy balance
      deficit of 180 kcal/kg can be ascribed to premature delivery. The cost of protein
      metabolism is the highest energy demanding process related to growth. The fact
      that nitrogen balance becomes positive within 72 h after birth places the newborn
      in a transitional situation of dissociated balance between energy and protein
      metabolism during early postnatal growth: skinfold thickness, dry body mass and
      fat decrease, while there is a gain in protein and increase in supine length.
      This particular situation ends during the second postnatal week and soon
      thereafter the rate of weight gain matches statural growth. The goals of the
      following review are to summarize data on total body water and energy metabolism
      in premature infants and to discuss how they correlate with physiological aspects
      of early postnatal growth.

PMID- 7734791
TI  - Substrate utilization during the first weeks of life.
AB  - It is assumed that substrate utilization changes markedly around birth, from
      mainly glucose utilization before, to glucose/fat utilization after birth. We
      studied substrate oxidation and turnover in preterm infants on the first day and
      during the first weeks of life. We found that only part of the glucose that is
      infused on the first day of life is oxidized, while glucose is also converted
      into fat at the same time. Almost half of the energy expenditure is provided by
      fat oxidation on day 7 and 28 of life. Fat oxidation is dependent on the type of
      fat oxidized; the rate of oxidation of medium chain triglycerides (MCT) is higher
      than that of long chain fatty acids. MCT can replace glucose as an energy source.
      Proteins contribute only to a small extent (approximately 7%) to the energy
      expenditure at all ages.

PMID- 7734792
TI  - Metabolic and energy balance in small- and appropriate-for-gestational-age, very
      low-birth-weight infants.
AB  - This study compared nutrient utilization and postnatal weight gain composition in
      eight appropriate for gestational age (AGA: birth weight 1293 +/- 107 g;
      gestational age 28.8 +/- 1.4 weeks) and eight symmetrically growth-retarded (SGA:
      birth weight 1110 +/- 230 g; gestational age 32.7 +/- 1.9 weeks), very low-birth
      weight (VLBW) infants. There was no significant difference in protein, mineral
      and energy intake between AGA and SGA infants. Nitrogen absorption (84 +/- 3 and
      83 +/- 4%) and nitrogen retention (356 +/- 48 and 352 +/- 43 mg/kg/day) were
      similar in both groups. Fat absorption tended to be lower in AGA (78 +/- 15%)
      than in SGA (87 +/- 4%) infants. Calcium, phosphorus and magnesium absorptions
      were similar in AGA and SGA infants. Metabolizable energy utilization was similar
      in both groups; about 55% was expended and 45% stored in new tissues. Energy
      expenditure was 58 +/- 4 kcal/kg/day in SGA infants and 61 +/- 9 kcal/kg/day in
      AGA infants. Weight gain and its composition were similar in both groups. We
      conclude that nutrient and energy utilization are similar in AGA and
      symmetrically growth-retarded, VLBW infants.

PMID- 7734793
TI  - Energy requirements in sick preterm babies.
AB  - The energy requirements of healthy preterm babies are well documented in the
      literature. However, the clinical load in neonatal intensive care units is due to
      sick preterm infants requiring prolonged mechanical ventilation, many of whom
      will develop bronchopulmonary dysplasia. It is this group in which knowledge of
      energy requirements is scanty. This group also has poor energy reserves and is
      often intolerant of enteral and parenteral nutrition. In this article, we will
      review methods of measurement of energy expenditure, methodological problems when
      applied to ill infants and published results of energy expenditure measurements
      in sick preterm babies. We will review the link between energy reserves, energy
      intake and energy expenditure. The problems of undernutrition in early postnatal
      life and possible consequences in adult life will be discussed.

PMID- 7734795
TI  - Maturative effects of hormones on the developing mammalian gastrointestinal
      tract.

PMID- 7734794
TI  - Molecular aspects of fat digestion in the newborn.

PMID- 7734796
TI  - Red blood cell fatty acid composition in low-birth-weight infants fed either
      human milk or formula during the first months of life.
AB  - The fatty acid composition of red blood cell (RBC) phospholipids in low-birth
      weight infants was determined immediately after delivery and during the first 3
      months of life. In the first study, infants were fed either human milk or two
      formulas with different fatty acid compositions but no long chain polyunsaturated
      fatty acids (LCPUFA). Both groups of formula-fed infants had significantly lower
      levels of docosahexaenoic acid (DHA) in RBC phospholipids compared with breast
      fed infants. RBC phospholipid DHA was similar in the two formula groups at all
      ages. In the second study, infants received either a non-supplemented or a LCPUFA
      supplemented formula. DHA remained stable in RBC phospholipids of infants
      supplemented with LCPUFA, whereas DHA decreased in RBC phospholipids of
      unsupplemented infants. These results confirm that adding DHA to formulas is more
      effective than increasing 18:3 n-3 content, in maintaining RBC phospholipid DHA
      levels.

PMID- 7734797
TI  - Essential fatty acid metabolism and requirements for LBW infants.
AB  - Humans are unable to synthesize linoleic acid (LA) (18:2 omega-6) and alpha
      linolenic acid (LNA) (18:3 omega-3). Most formulas provide ample LA, yet infants
      are at risk for omega-3 deficiency unless they are fed human milk. Neonates born
      at 30 weeks received human milk or were randomized to three formulas: formula A,
      based on corn oil, similar to old commercial formula; formula B, based on soy oil
      supplied LNA; or formula C, a product similar to B with added marine oil to
      provide docosahexaenoic acid (22:6 omega-3). The fatty acids of plasma and red
      blood cells had marked diet-induced differences. The rod photo-receptor tests
      demonstrated higher threshold and decreased sensitivity in the omega-3-deficient
      infants. Visual acuity also showed improved function of the brain cortex in the
      human milk and group C infants at follow-up at 57 weeks. These results suggest
      that omega-3 fatty acids are needed for optimal development of visual function.

PMID- 7734798
TI  - Protein turnover in low-birth-weight (LBW) infants.
AB  - Protein deposition in infants results from an equilibrium between protein
      synthesis and degradation. Separate measurements of these two simultaneous
      processes are required for a better understanding of the mechanisms and
      regulation of growth. Current methods of assessment of whole-body protein
      synthesis and degradation rely on the use of stable isotope labelled tracer and
      are briefly reviewed and discussed ("end-products" and precursor method) with an
      emphasis on their practical and conceptual limits. Overall, protein turnover is
      higher in infants than in adults, but there are discrepancies within the
      literature, which are mostly due to methodological differences. The relationships
      between energy expenditure and protein turnover and the mechanisms of protein
      deposition during feeding (which is inhibition of protein degradation rather than
      stimulation of protein synthesis) are also described. Finally, we review the few
      available data on protein turnover modifications induced by various
      pathophysiological states.

PMID- 7734799
TI  - Protein fortification of human milk for feeding preterm infants.

PMID- 7734800
TI  - Metabolic balance studies and plasma amino acid concentrations in preterm infants
      fed experimental protein hydrolysate preterm formulas.
AB  - The aim of this study was to investigate absorption and retention of nitrogen,
      fat, calcium, phosphorus and magnesium, as well as plasma amino acid
      concentrations in 19 preterm infants fed three experimental protein hydrolysate
      preterm formulas (PTHF): seven received a preterm formula based on 100% whey
      hydrolysate protein (PTHF1), seven other infants were fed a preterm formula based
      on a mixture of 78% whey and 22% casein hydrolysed protein (PTHF2) and a third
      group of five infants were fed the same type of protein hydrolysate (78/22)
      enriched with histidine (PTHF3). Metabolic balances (n = 39) and plasma amino
      acid concentrations (n = 12) in preterm infants fed a standard preterm formula
      (whey/casein: 60/40) were included as a control group. Amino acid composition of
      the formulas was determined after complete hydrolysis with 12 N HCl. Compared
      with the standard preterm formula, the use of protein hydrolysate formulas led to
      a decrease in nitrogen and phosphorus absorption without modification of
      retention. Net absorption of calcium and magnesium was not significantly
      different in the four groups but calcium intake necessary to obtain calcium
      retention similar to the standard preterm formula was higher in the infants fed
      the hydrolysate formulas. Plasma amino acid concentrations were related to the
      amino acid composition of the formulas. Compared with the standard preterm
      formula, all three protein hydrolysate formulas led to a significant increase in
      plasma threonine, and a decrease in tyrosine and phenylalanine concentrations. In
      addition, there was an important reduction in plasma histidine concentrations
      with PTHF1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734801
TI  - 17th International Symposium on Growth and Growth Disorders. Proceedings of a
      meeting. Barcelona, April 1994.

PMID- 7734803
TI  - Body proportions in patients with homozygous beta-thalassaemia.

PMID- 7734802
TI  - Endocrine aspects of thalassaemia major.

PMID- 7734804
TI  - Growth patterns in patients with thalassaemia major.

PMID- 7734805
TI  - Psychosocial assessment of children with short stature: a preliminary report.
AB  - Previous studies that have examined the psychosocial adjustment of children with
      short stature have often been flawed, for two main reasons: first, a lack of
      sample homogeneity and, secondly, the measures of adjustment used have been
      limited in terms of their sensitivity. This paper examines psychological
      functioning in the following four broad areas: cognition, social behaviour,
      emotional adjustment and self-concept. A sample of children referred to growth
      clinics (mean height below -2 SDS) and a comparison group, recruited from the
      referred childrens' classes at school, were assessed. Children were prepubertal
      (age range, 6-11 years) and had no organic cause for their short stature. Parent,
      teacher and peer reports were used in the assessment, which included sociometric
      measures in the classroom. The children with short stature described themselves
      as equally well supported as the comparison children in terms of social support
      by parents, teachers, peers and friends. Peers reported the short children to be
      well accepted within their class. Compared with control children, there was a
      trend for short children to be described by their peers as socially better
      adjusted than average. Teacher and parental accounts revealed significant group
      differences in terms of reported behaviour, with poorer attention and more
      thought problems among the children with short stature. Further analysis
      suggested, however, that their slightly lower IQ than children of normal height
      (95.8 +/- 18.7 (mean +/- SD) compared with 105 +/- 15.4) accounted for a greater
      proportion of the variance in these findings than short stature per se. There is
      little evidence to indicate that short prepubertal children are psychosocially
      maladjusted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734806
TI  - Thyroid disorders and diabetes mellitus as complications of thalassaemia major.

PMID- 7734807
TI  - Growth hormone treatment of idiopathic short stature: analysis of the database
      from KIGS, the Kabi Pharmacia International Growth Study.
AB  - Within the Kabi Pharmacia International Growth Study (KIGS) database, there is
      information on 1017 (700 male/317 female) patients with idiopathic short stature
      (ISS). These patients were started on recombinant human growth hormone (GH) at a
      median age of 10.8 years, a bone age of -1.8 SDS, a height of -2.6 SDS and a
      predicted adult height (PAH) (Bailey-Pinneau method) of -2.5 SDS. The median dose
      of GH was 0.6 IU/kg body weight/week and the frequency of injections was
      six/week. According to the relationship with target height the patients were
      classified into 'familial short stature (FSS)' (height SDS > target height SDS 
      1.28) and into 'non-FSS' (height SDS < target height SDS -1.28). During the first
      year of GH treatment there was an overall increment in the median height velocity
      from 4.4 to 7.4 cm/year. Over 3 years of GH treatment, cross-sectional analysis
      demonstrated an overall increment in median PAH of 1.2 SDS. There was a positive
      correlation between gain in PAH and the GH dose (n = 202, r = 0.18, p < 0.01)
      during the first year. Longitudinal analysis in 84 patients showed an overall
      increment of PAH of 0.7 SDS over 2 years of treatment. When applying the KIGS
      first-year prediction model for patients with idiopathic GH deficiency on cohorts
      of prepubertal children with FSS and non-FSS, a lower responsiveness to GH in the
      non-FSS group was observed. It is concluded that higher than substitutive doses
      of GH are required for the long-term improvement of growth in ISS.

PMID- 7734808
TI  - Adolescence in evolutionary perspective.

PMID- 7734809
TI  - Prediction of final height in short, normal and tall children.
AB  - Measurements of final height were made on more than 4000 children in the final
      grade of school in Gothenburg in 1992; at the same time, mid-parental heights
      were recorded. These data were combined with other information (sex, length of
      gestation, size at birth, estimated age at peak height velocity (PHV) and height
      measurements made before 8 years of age) and used in a multiple regression
      analysis to assess the strength of the linear relationship between attained final
      height and these other potentially predictive measures of adult height. The R2
      value increased from 0.16 at birth to 0.64 when the child was 8 years old. The
      inclusion of mid-parental height in the regression analysis contributed
      significantly to the explained variation in final height, especially at the
      earlier ages; the further addition of size at birth and age at PHV provides a
      small increase in the explained variation. The probability that the final height
      of a child will be below -2 or above +2 standard deviation scores (SDS) was
      assessed, based on previous SDS values for height when younger and on mid
      parental height SDS. As a result of the large sample size included in the
      analyses, considerable confidence can be placed on the accurate prediction of
      final height values in the range -2.5 to +2.5 SDS.

PMID- 7734810
TI  - The cellular mechanism of growth hormone signal transduction.

PMID- 7734811
TI  - In vitro effects of growth hormone in adipose tissue.

PMID- 7734812
TI  - Effects of growth hormone on lipolysis in humans.

PMID- 7734813
TI  - Effects of recombinant human growth hormone on adipose tissue in adults with
      growth hormone deficiency.

PMID- 7734814
TI  - Is there a place for short bursts of growth hormone treatment in short children
      without significant growth hormone deficiency?

PMID- 7734815
TI  - Computer diagnosis of skeletal dysplasias and malformation syndromes.

PMID- 7734817
TI  - A fully automated bone-ageing system.

PMID- 7734816
TI  - Assessment of bone ages by the Tanner-Whitehouse method using a computer-aided
      system.
AB  - A computer-aided system to estimate bone age based on Fourier analysis was
      assessed by reference to the original radiographs used to produce the Tanner
      Whitehouse 2 (TW2) standards for the radius, ulna and short finger bones. The
      computer-aided system involved matching a template of each bone to the scanned
      image of the radiograph. The computer then generated a stage of bone maturity,
      individual and total bone scores and a value for bone age. The bone ages assessed
      by the computer-aided system were no different from the original TW2 reference
      values, indicating the applicability of the system. The system was used to assess
      the bone ages of tall Dutch girls, and the results obtained were compared with
      more traditional assessments made by an experienced rater. For the radiographs
      from the tall girls, there was good agreement for individual bones between this
      method and the traditional assessment by the rater, but less agreement for the
      total 13-bone score and bone age.

PMID- 7734818
TI  - Preliminary report on the validation of a grammar-based computer system for
      assessing skeletal maturity with the Tanner-Whitehouse 2 method.
AB  - A series of hand and wrist radiographs was assessed manually by two individuals
      and by a fully automated computer system for determining bone age. Assessments
      were repeated after 1 month to determine variability between and within the
      methods of bone age assessment. There was slight intra-observer variation, but
      complete reproducibility when assessments were made by computer. The variation
      between the human assessors was less than that between human and computer
      assessments. The difference between overall maturity scores made by the human
      observer and the computer system was, however, acceptably small, and the majority
      of assessments were the same. It is concluded this computer system for assessing
      bone age in normal children is reliable and accurate, but that it needs to be
      validated against a much larger set of radiographs.

PMID- 7734819
TI  - Effects of growth hormone and insulin-like growth factors on the central nervous
      system.

PMID- 7734820
TI  - Characterization of growth hormone binding sites in rat brain.
AB  - The binding of 125I-labelled rat growth hormone (GH) to different areas in the
      brain was studied in male Sprague-Dawley rats. A high density of GH binding was
      found in the choroid plexus, hypothalamus, hippocampus, pituitary and spinal
      cord, whereas a lower binding density was observed in the cortex. Binding of the
      hormone to the various brain regions was age dependent. Binding was also
      dependent on time, pH and protein concentration. The binding affinity of the
      labelled hormone to choroid plexus was 4.3 per nmol/l and the binding capacity
      was 33.4 nmol/mg protein. The corresponding figures for binding of 125I-labelled
      GH to hypothalamus were 5.6 per nmol/l and 21.6 nmol/mg protein. By sodium
      dodecyl sulphate electrophoresis of the cross-linked hormone-receptor complexes,
      molecular weights of 60,000 and 61,000 were determined for the binding units in
      the choroid plexus and hypothalamus, respectively. It was further indicated that
      the binding unit for rat GH was distinct from that for prolactin.

PMID- 7734821
TI  - What is the clinical significance of biochemical markers of growth and bone
      metabolism?

PMID- 7734822
TI  - Importance of staphylococci that produce nanogram quantities of enterotoxin.
AB  - Many staphylococcal strains produce enterotoxin, the toxin that is the cause of
      staphylococcal food poisoning. If a strain is enterotoxigenic it is possible for
      it to be involved in food poisoning. The gel diffusion methods were the first
      methods developed for detection of the enterotoxins and were thought adequate to
      detect their production. However, they were not adequate to detect enterotoxin in
      foods involved in food poisoning. When researchers began using the sensitive
      methods, such as enzyme-linked immunosorbent assay (ELISA) and reversed passive
      latex agglutination (RPLA), to check strains for enterotoxin production, some
      strains produced nanogram quantities of enterotoxin. When it was reported that
      several coagulase-negative species produced less than 10 ng/ml of enterotoxin, it
      was imperative to determine whether these strains produced enough enterotoxin in
      foods to cause food poisoning. At the present time research is under way to
      determine whether these strains produce enough enterotoxin in foods to cause food
      poisoning.

PMID- 7734823
TI  - Seroprevalence of HCV, HAV, HBV, HDV, HCMV and HIV in high risk groups/Frankfurt
      a.M., Germany.
AB  - During the period from August 1991 to April 1993, serum samples originating from
      different risk groups were tested for antibodies against hepatitis C virus (HCV),
      using a second-generation ELISA. The highest HCV seroprevalence levels were
      observed in haemophiliacs (87.0%) and intravenous drug abusers (IVDA) (78.9%).
      The HCV-seropositivity rates of polytransfused and organ transplant recipients
      were nearly identical (18.4% vs. 16.8%). Significantly lower HCV-seroprevalence
      rates were determined in chronic haemodialysis patients (8.1%) and homo/bisexuals
      (10.0%). The lowest HCV seroprevalence levels were found in the groups of female
      prostitutes (1.4%) and health care staff (0.8%). A strong correlation between HCV
      seropositivity and the presence of antibodies against HIV-1, HBc and HCMV was
      observed. There was also an association between HCV seropositivity and HAV. The
      seroprevalence of HDV and the proportion of HBsAg and HBeAg carriers was not
      significantly influenced by HCV serostatus. The incidence of HCV infection in
      renal transplant recipients was 3.9%. In 10 (6.5%) patients, anti-HCV
      seroconversion was observed in the immediate post-transplantation period followed
      by a decrease of the index value and finally, disappearance of antibodies at the
      end of the study. Antibodies passively acquired through intravenous
      immunoglobulin (IVIG) donation may account for overestimation of HCV
      seroprevalence in retrospective seroepidemiological surveys as established by our
      findings.

PMID- 7734824
TI  - Detection of sialidase activity in Oerskovia (Cellulomonas) turbata.
AB  - The enzyme N-acylneuraminate glycohydrolase, E.C. 3.2.1.18 (sialidase or
      neuraminidase) was detected in all five strains of Oerskovia (Cellulomonas)
      turbata and in a further strain isolated from clinical material. The detection of
      sialidase was performed by different methods, i.e. colorimetric determination of
      liberated chromogen, immunoelectrophoresis and paper chromatography. The
      Oerskovia turbata sialidase is able to cleave different linkages between N
      acylneuraminic acid and the carbohydrate chains of oligosaccharides or
      polysaccharides and of glycoproteins, i.e. the 2-->3, 2-->6, and 2-->8 linkages.
      Finally, the ecologic and pathogenic role of neuraminidase is discussed.

PMID- 7734826
TI  - Genetic analysis of dermatophilus spp. using multilocus enzyme electrophoresis.
AB  - Multilocus enzyme electrophoresis was used to examine a collection of 41 mainly
      Australian isolates of Dermatophilus congolensis that had been cultured from
      sheep, cattle, horses, a goat, a marsupial and Chelonids. Allelic variation was
      examined at 16 enzyme loci. The isolates were divided into eight distinct
      electrophoretic types (ETs) with a mean genetic diversity per locus of 0.41. The
      three isolates from Chelonids represented a distinct clone in ET 1 which was
      separated from the remaining cluster of isolates of D. congolensis by a genetic
      distance of 0.852. These findings supported a previous proposal that the isolates
      from Chelonids represent a new species of Dermatophilus. The other 38 D.
      congolensis isolates were separated into two divisions (I and II) by a genetic
      distance of 0.560. The divisions were both subdivided into groups that either
      only contained alpha-hemolytic or beta-hemolytic isolates, but all isolates in
      each ET had only one hemolytic pattern. Isolates originating from the same animal
      species, or from the same geographic location, were not all closely related
      genetically. The allocation of isolates into ETs correlated well with their
      distribution into DNA restriction endonuclease analysis patterns previously
      established for the collection. Although relatively few distinct strains of D.
      congolensis were identified amongst the collection, significant genetic diversity
      existed within this population.

PMID- 7734825
TI  - Investigations of culture and properties of Afipia spp.
AB  - The culture conditions of Afipia felis, A. broomeae, A. clevelandensis and three
      unnamed Afipia genospecies were investigated on BCY agar supplemented with
      different substances known as growth factors of Legionella spp. and, furthermore,
      with sodium chloride and other salts. The organisms were found to be susceptible
      to a certain degree to byproducts of the autoclaving which are scavenged by
      activated by charcoal. Growth was weakly enhanced by ferric pyrophosphate,
      cystein.HCl, and alpha-ketoglutarate. These substances are no obligatory growth
      factors. The optimal pH value was about 6.8. Afipia spp. showed a strong
      susceptibility to NaCl and other salts. They possess phosphatase, phosphoamidase,
      phosphodiesterase, a weak sulfatase, glycine aminopeptidase, and L-lysine
      aminopeptidase. The strains differed with regard to other proteases and
      aminopeptidases. The decimal reduction times of A. felis at 55 degrees C and 60
      degrees C were 11 min, < 1 min, respectively.

PMID- 7734827
TI  - Isolation of a Legionella pneumophila strain serologically distinguishable from
      all known serogroups.
AB  - A Legionella pneumophila strain (Jena-1) was isolated from a water sample
      collected from the hot water system of a scientific institution in Jena, Germany.
      Protein profile, ubiquinone and fatty acid content of the outer membrane were in
      accordance with those described for other Legionella pneumophila serogroups. DNA
      extracted from strain Jena-1 gave a positive amplification by using an L.
      pneumophila (mip)-specific commercially available PCR-kit confirming that the
      isolate belonged to the species L. pneumophila. Strain Jena-1 reacted with a
      monoclonal antibody specific for the major outer membrane protein of the species
      L. pneumophila and another one recognizing a lipopolysaccharide epitope of L.
      pneumophila serogroups 2-6, 8-10, and 12-15. Cross-absorption studies using
      absorbed and unabsorbed rabbit antisera to serogroups 1-15 and the newly isolated
      strain showed that strain Jena-1 cross-reacted mainly with serogroup 4, and to a
      lesser extent, with serogroups 5, 8, and 10. These cross-reactions could be
      removed by cross-absorption without significant effects on the homologous titres.
      It is concluded that strain Jena-1 represents a new serogroup of Legionella
      pneumophila.

PMID- 7734828
TI  - Isolation of Yersinia pseudotuberculosis from river waters in Japan and Germany
      using direct KOH and HeLa cell treatments.
AB  - Yersinia pseudotuberculosis was recovered from precipitates directly treated with
      KOH and/or HeLa cell in 25.7% of 680 river water samples collected in Japan.
      Recovery was nil in similar samples from Germany. Treatment of precipitates by
      KOH and infection of HeLa cells, respectively, is an expedient and selective
      means for isolation of Y. pseudotuberculosis from such samples.

PMID- 7734829
TI  - Adhesion to and invasion of HeLa cells by Helicobacter pylori.
AB  - Eight clinical isolates and two reference strains of Helicobacter pylori were
      studied with regard to their interactions with HeLa cells. All the isolates
      adhered poorly to HeLa cells and the number of invasive bacteria was very low. No
      correlation was found between the adherence and invasiveness of the isolates on
      one hand, and the corresponding patients having ulcer or non-ulcer disease, or
      the ability of the strains to produce cytotoxin and to induce an oxidative burst
      of human polymorphonuclear leukocytes without opsonins, on the other. These
      results indicate that invasion of epithelial cells would play no important role
      in the pathogenesis of infections caused by H. pylori.

PMID- 7734830
TI  - Phospholipase A activity in Pseudomonas aeruginosa.
AB  - Our study describes the production, purification and properties of an enzyme from
      Pseudomonas aeruginosa displaying the properties of phospholipase A. Maximal
      amounts of enzyme could be detected in the culture supernatant when the bacterium
      was grown for 3 to 5 days at 37 degrees C in stirred flask cultures containing
      brain heart infusion. The enzyme was purified by polyethylenimine precipitation
      and ammonium sulfate precipitation followed by gel filtration. In sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, the enzyme preparation exhibited two
      bands with molecular weights of 13.5 and 60 kD, respectively. Correspondingly,
      two peaks of the same molecular weight could be demonstrated by high performance
      size exclusion chromatography. The activity toward the sn-2 ester binding of
      phospholipids was characterized and found to be highest towards
      phosphatidylcholine. Enzymatic activity was not influenced by the addition of
      calcium or EDTA while magnesium and strontium caused a decrease of activity. The
      lyophilized enzyme was found to be stable when stored at -70 degrees C and most
      active at pH 8.0.

PMID- 7734831
TI  - Isolation and characterization of a mitogen characteristic of group A
      streptococci (Streptococcus pyogenes).
AB  - It has been supposed for many years that group A streptococci may elaborate more
      than the three well known erythrogenic toxins A, B or C (ETA, ETB, ETC). The
      analysis of the culture supernatant of streptococcal strain 27297 carrying
      neither genes for ETA nor ETC revealed mitogenic activity at pH 7.3 in
      isoelectric focusing. This mitogen of strain 27297 was purified by hydrophobic
      adsorption to Phenyl-Sepharose following FPLC chromatography on a Mono S column
      resulting in two proteins with mitogenic activity called AX and BX, respectively.
      Both differed in only one aminoterminal residue. The mitogenic activity of BX
      lacking one aminoterminal arginine was found to be about 100 times higher than
      that of AX. The aminoterminus of BX does not correspond to a predictable cleavage
      site for signal peptidase. We assume that BX was produced after translation by
      cleavage of the mature protein or the AX molecule with streptococcal proteinase
      (ETB) or an arginylaminopeptidase which is detectable on whole cells. The
      purified proteins BX and AX showed molecular weights of about 27 kDa in SDS
      electrophoresis and isoelectric points of 8.3 (AX) and 7.3 (BX) in isoelectric
      focusing, respectively. Both proteins were produced by practically all group A
      strains tested but not by groups B, C, G or H streptococci. Therefore, AX or BX
      seem to be proteins characteristic of group A streptococci.

PMID- 7734832
TI  - Therapy of penicillin-resistant pneumococcal meningitis.
AB  - Antimicrobial therapy of pneumococcal meningitis has been altered in recent years
      based on changes in pneumococcal susceptibility patterns, with emergence of
      strains that are either relatively or highly resistant to penicillin G (minimal
      inhibitory concentrations of 0.1-1.0 micrograms/ml and > or = 2 micrograms/ml,
      respectively. In areas of the world where relatively penicillin-resistant strains
      of Streptococcus pneumoniae are present, the third generation cephalosporins
      (either cefotaxime or ceftriaxone) should be used as empiric therapy, and for
      highly penicillin-resistant pneumococcal strains, vancomycin (with or without
      rifampin) is recommended. It is imperative that susceptibility testing be
      performed on all cerebrospinal fluid pneumococcal isolates to guide the choice of
      antimicrobial therapy. Vaccination recommendations with the 23-valent
      pneumococcal vaccine should also be strictly enforced for use in appropriate
      populations that are at increased risk of pneumococcal infections.

PMID- 7734833
TI  - Metronidazole susceptibility testing of Helicobacter pylori with the PDM
      epsilometer test (E test).
AB  - The bacteriostatic activity of metronidazole against Helicobacter pylori was
      determined with the PDM epsilometer test (E test) and with an agar dilution test.
      Both methods correlated in the minimum inhibitory concentration (MIC) ranges (<
      or = 0.5- > 32 mg/l) and in the MIC 50 (E test: 1 mg/l; agar dilution test: 2
      mg/l) and MIC 90 (> 32 mg/l) values. However, comparison of test results of
      single strains revealed that 14 out of 105 strains (13.3%) were classified as
      resistant by one method but classified susceptible by the other. The correlation
      coefficient of 0.71 also indicated a low congruence of test results. It is
      concluded that both methods should be used in order to ascertain all strains
      resistant to metronidazole.

PMID- 7734834
TI  - Influence of propionibacterium avidum KP-40 on the proliferation, maturation,
      emigration and activity of thymocytes and monocytes.
AB  - Inactivated cells of Propionibacterium avidum KP-40 could be shown to induce
      thymocyte proliferation and maturation in BALB/c-mice after intraperitoneal
      administration of the optimal immunomodulating dosage (1 mg per mouse). The
      increase in thymus weight and thymocyte numbers per mg organ weight was most
      pronounced and statistically significant 10 days after P. avidum KP-40
      administration. Determinations of lymphatic subsets revealed a considerable up
      regulation of mature cells expressing helper/inducer (L3T4+) or
      cytotoxic/suppressor (Lyt-2+) phenotypes and immature cells presenting both
      L3T4+/Lyt-2+ antigens. Obviously, P. avidum KP-40 administration accelerated
      murine thymocyte proliferation and maturation. Counts of BALB/c-mouse peripheral
      blood lymphocytes (PBL) and monocytes (PBM) revealed statistically significant
      increases after P. avidum KP-40 administration with peak values after 6-10 days.
      The determination of activated PBL (expressing interleukin-2 receptors) or PBM
      (expressing MAC-3 antigens) proved that P. avidum KP-40 induced a potent
      immunostimulation since counts of these cells were significantly enhanced after
      P. avidum KP-40 treatment.

PMID- 7734835
TI  - Replication and persistence of coxsackieviruses B3 in human fibroblasts.
AB  - Although in some cases a carrier state of Coxsackieviruses in human fibroblasts
      was described, the persistence mechanism has remained unknown. Our results
      demonstrate a replication of Coxsackievirus B3 (CVB3) in diploid human
      fibroblasts that is dependent on the virus strain as well as on the cell line
      involved. Two CVB3 Nancy strains could be multiplied over more than 10 passages
      in cell line H, whereas CVB3 strains SH"C" and SH"W" did not longer form
      infectious virus following several passages in these fibroblasts. None of the
      CVB3 strains replicated in cell lines J and K after a few passages. These results
      were not influenced by variations of culture conditions such as duration of
      incubation (3 or 7 days), temperature (33 or 37 degrees C) or application of
      trypsin. In line H, only 3-5 per cent of human fibroblasts were virus-infected.
      This was demonstrated by 1. antigen evidence by immunofluorescence, 2.
      determination of infectious centres, and 3. virus reproduction in dependence on
      MOI of the virus. We observed a carrier state of CVB3 Nancy strains over 16 cell
      passages in line H fibroblasts infected once. As shown in virus passage
      experiments, only few cells were productively infected. An addition of specific
      anti-CVB3 antiserum terminated this persistent infection. Generally, no
      cytopathic effect was observed. However, in one case a cell destruction by CVB3
      Nancy "P" at the end of the life-time of the carrier cells could be found. This
      virus caused a complete cytopathic effect during more than 10 passages in line H
      and could still be neutralized by CVB3-specific antiserum.

PMID- 7734836
TI  - Transduction of the stress signal and mechanisms of transcriptional regulation of
      heat shock/stress protein gene expression in higher eukaryotes.
AB  - This review deals with the transcriptional regulation of heat shock or stress
      genes that are present in every organism studied to date. While some of these
      genes are expressed constitutively and appear to be involved in basic cellular
      processes such as protein synthesis and maturation, assembly of protein
      complexes, and intracellular trafficking, others are normally silent or are
      expressed at low levels. Expression of the latter genes is enhanced when cells
      are subjected to stressful conditions such as elevated temperature and other
      physical and chemical insults or at specific stages of organismal development.
      The upregulation of these genes correlates with the development of tolerance to
      subsequent, similar insults. Upregulation following environmental insults appears
      to be mediated by heat shock transcription factor. This article summarizes what
      is known about the promoters of regulated stress genes in higher eukaryotes and
      the mechanisms by which heat shock transcription factor or developmental
      regulators control their activation. Recent data pointing to a possible
      connection between the activation of stress genes and general signal transduction
      pathways are also discussed, as they suggest an integration of the stress
      response and other cellular control mechanisms.

PMID- 7734837
TI  - Experimental analysis of chromatin function in transcription control.
AB  - Chromatin structure plays a crucial role in the regulation of eukaryotic gene
      transcription. Nucleosomes and higher orders of chromatin structure repress
      promiscuous gene expression by increasing its dependence on the function of
      activator proteins that regulate transcription in eukaryotic cells. Here we
      review several parameters governing the dynamic interactions between
      transcription factors and chromatin structures. These include functions of the
      core histones and their modification by acetylation, histone H1, HMG proteins,
      nucleosome positioning, DNA replication, cooperative nucleosome-binding by
      transcription factors, histone chaperones and nucleosome displacement, the
      SWI/SNF protein complex, and higher-order domains of chromatin structure. All of
      these impact on the interactions of transcription factors with chromatin
      templates. Experimental analysis of these parameters provides new insights into
      mechanisms of eukaryotic transcription regulation.

PMID- 7734838
TI  - A calculation of all possible oligosaccharide isomers both branched and linear
      yields 1.05 x 10(12) structures for a reducing hexasaccharide: the Isomer Barrier
      to development of single-method saccharide sequencing or synthesis systems.
AB  - The number of all possible linear and branched isomers of a hexasaccharide was
      calculated and found to be > 1.05 x 10(12). This large number defines the Isomer
      Barrier, a persistent technological barrier to the development of a single
      analytical method for the absolute characterization of carbohydrates, regardless
      of sample quantity. Because of this isomer barrier, no single method can be
      employed to determine complete oligosaccharide structure in 100 nmol amounts with
      the same assurance that can be achieved for 100 pmol amounts with single
      procedure Edman peptide or Sanger DNA sequencing methods. Difficulties in the
      development of facile synthetic schemes for oligosaccharides are also explained
      by this large number. No current method of chemical or physical analysis has the
      resolution necessary to distinguish among 10(12) structures having the same mass.
      Therefore the 'characterization' of a middle-weight oligosaccharide solely by NMR
      or mass spectrometry necessarily contains a very large margin of error. Greater
      uncertainty accompanies results performed solely by sequential enzyme degradation
      followed by gel-permeation chromatography or electrophoresis, as touted by some
      commercial advertisements. Much of the literature which uses these single methods
      to 'characterize' complex carbohydrates is, therefore, in question, and journals
      should beware of publishing structural characterizations unless the authors
      reveal all alternate possible structures which could result from their
      analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734839
TI  - A family of UDP-GlcNAc/MurNAc: polyisoprenol-P GlcNAc/MurNAc-1-P transferases.

PMID- 7734840
TI  - Substrate specificity of Flavobacterium meningosepticum Endo F2 and endo F3:
      purity is the name of the game.

PMID- 7734841
TI  - Occurrence and biological roles of 'proximal glycanases' in animal cells.
AB  - Glycosylation of particular proteins and lipids has become generally acknowledged
      as being important for these molecules to express their functions in various
      biological events. However, much less attention has been paid to the biological
      significance of deglycosylation of such once-glycosylated molecules in the
      context other than catabolism and recycling in the lysosome. Recently, in various
      kinds of animal cells and tissues we found non-lysosomal peptide: N-glycanase
      (PNGase) activities. Before these findings, PNGase was only known in plants and
      bacteria, and our findings indicated that de-N-glycosylation reaction catalysed
      by PNGase occurred universally in bioorganisms, and might function as a certain
      biologically important modification, not as a degradative pathway. Now, we put
      forward and extend the concept to all the glycoconjugates that deglycosylation as
      well as glycosylation occur as a universal cellular system to modulate the
      function of the present molecules, and postulate 'proximal glycanases'
      (PROXIases) as enzymes that are responsible for the detachment of intact glycan
      from glycoconjugates and form free glycan and apo-glycoconjugates. In this
      article, we review the occurrence and possible function of proximal glycanases in
      animal cells.

PMID- 7734842
TI  - Characterization of ganglioside associated with the thyrotrophin receptor.
AB  - The receptor protein for thyrotrophin (thyroid-stimulating hormone; TSH) is
      associated with a glycosphingolipid moiety. The protein belongs to the family of
      receptors that couple to guanine nucleotide binding proteins; the
      glycosphingolipid contains sialic acid and belongs to the family of gangliosides.
      This report defines the structure of the receptor ganglioside in the Fisher rat
      thyroid cell line (FRTL-5). Receptor protein was purified by TSH affinity
      chromatography from FRTL-5 cells, biosynthetically labelled with [3H]galactose
      and [3H]glucosamine, and resolved by SDS-PAGE. A single radiolabelled band of Mr
      approximately 80 kDa, corresponding to the predicted size of the cloned receptor,
      contained ganglioside. Gangliosides were extracted from unlabelled receptor
      protein after SDS-PAGE and probed on TLC plates with 125I-labelled Limax flavus
      agglutinin or the B subunit of cholera toxin, before and after digestion with
      Vibrio cholerae sialidase or beta-galactosidase. The TSH receptor (TSH-R)
      ganglioside belongs to the gangliotetraose family, having sialic acid attached to
      both galactose molecules. Its sialic acid is devoid of negative charge because of
      the formation of internal esterlactones. Its structure is lactonized N
      acetylneuraminyl-(alpha 2-->3)galactosyl(beta 1-->3)-N-acetylgalactosaminyl(beta
      1-->4)-[N-acetylneuraminyl(alpha 2-->3)]galactosyl(beta 1-->4)glucosyl(beta 1-
      >1)ceramide (GDla-lactone). Ganglioside lactones have not been previously
      described as components of thyroid cells. They are highly rigid and are more
      likely than their parent structures to serve as molecular recognition sites and
      elicit immunoreactivity. Identification of this unique ganglioside intimately
      associated with the TSH receptor implies that it has an integral role in receptor
      structure and function.

PMID- 7734843
TI  - Human serum contains a chitinase: identification of an enzyme, formerly described
      as 4-methylumbelliferyl-tetra-N-acetylchitotetraoside hydrolase (MU-TACT
      hydrolase).
AB  - Since 1988 an endoglucosaminidase, provisionally named MU-TACT hydrolase, has
      been known that hydrolyses the artificial substrate 4-methylumbelliferyl-tetra-N
      acetyl-chitotetraoside (MU-[GlcNAc]4, where GlcNAc is N-acetylglucosamine). The
      biological function of the enzyme was unknown. In this paper evidence is
      presented showing that this endoglucosaminidase from human serum is in fact a
      chitinase that is different from lysozyme. The facts sustaining this finding are:
      (i) the identification of the products formed from MU-[GlcNAc]3 and [GlcNAc]2;and
      [GlcNAc]3; (ii) chitin and ethylene glycolchitin can be degraded by the enzyme;
      (iii) the chitinase inhibitor allosamidin also inhibits the action of MU-TACT
      hydrolase from human serum; (iv) no hydrolysis of the lysozyme substrate
      Micrococcus lysodeikticus. The enzyme also occurs in rat liver. It was
      demonstrated that upon Percoll density gradient centrifugation the enzyme from
      this tissue distributed parallel to the lysosomal marker enzymes beta-N
      acetylhexosaminidase and beta-galactosidase, indicating a lysosomal localization
      for this enzyme. It is proposed that the enzyme functions in the hydrolysis of
      chitin, to which mammals are frequently exposed during infection by pathogens.

PMID- 7734844
TI  - Molecular dynamics simulations of oligosaccharides and their conformation in the
      crystal structure of lectin-carbohydrate complex: importance of the torsion angle
      psi for the orientation of alpha 1,6-arm.
AB  - The conformation of the heptasaccharide Man-alpha 1,6-(Man-alpha 1,3)(Xyl-beta
      1,2)-Man-beta 1,4-GlcNAc2-beta 1,4-(L- Fuc-alpha 1,3)-GlcNAc1, the carbohydrate
      moiety of Erythrina corallodendron lectin (EcorL), the hexasaccharide Man-alpha
      1,6-(Man-alpha 1,3) (GlcNAc-beta 1,4)-Man-beta 1,4-GlcNAc-beta 1,4-GlcNAc and
      their disaccharide fragments have been studied by molecular dynamics (MD)
      simulations for 1000 ps with different initial conformations. In the isolated
      heptasaccharide, the most frequently accessed conformation during MD has a psi
      value of 180 degrees around Man-alpha 1,6-Man linkage. This conformation is
      stabilized by the formation of a hydrogen bond between the carbonyl oxygen of
      GlcNAc2 with the O3/O4 hydroxyls of the alpha 1,6-linked mannose residue. The
      conformation of the heptasaccharide found in the crystal structure of the EcorL
      lactose complex (Shaanan et al., Science, 254, 862, 1991), that has a psi value
      of approximately 76 degrees around Man-alpha 1,6-Man linkage, is accessed,
      although less frequently, during MD of the isolated oligosaccharide. The phi,
      psi, chi = 58 degrees, -134 degrees, -60 degrees conformation around Man-alpha
      1,6-Man fragment observed in the crystal structure of the Lathyrus ochrus lectin
      complexed with a biantennary octasaccharide (Table I in Homans, S.W.,
      Glycobiology, 3, 551, 1993) has also been accessed in the present MD simulations.
      These psi values for the alpha 1,6-linkage, which are observed in the protein
      carbohydrate crystal structures and are accessed in the MD simulations, though
      occasionally, have not been predicted from NMR studies. Furthermore, these
      different values of psi lead to significantly different orientations of the alpha
      1,6-arm for the same value of chi. This contrasts with the earlier predictions
      that only different values of chi can bring about significant changes in the
      orientation of the alpha 1,6-arm. The MD simulations also show that the effects
      of bisecting GlcNAc or beta 1,2-xylose are very similar on the alpha 1,3-arm and
      slightly different on the alpha 1,6-arm.

PMID- 7734845
TI  - Mucin synthesis in immortalized canine tracheal epithelial cells.
AB  - To study the regulation of mucin synthesis in canine tracheal epithelial cells,
      it is desirable to establish a cell line which synthesizes mucin continuously. We
      adopted the approach of immortalizing canine tracheal epithelial cells using a
      vector encoding the human papillomavirus (type 18) E6 and E7 genes. The E6 and E7
      genes are essential and sufficient for the immortalization of human genital
      keratinocytes, as well as human tracheal epithelium. Primary epithelial cells
      from dog trachea were transfected with a vector containing HPV18 genes E6 and E7.
      The resultant cells (CT1) were cloned and maintained in selective medium
      supplemented with growth factors and hormones. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) analysis indicated the expression of the canine tracheal
      mucin (CTM) mRNA in these cells. The half-life of the CTM mRNA was found to be 45
      60 min. Incorporation of labelled precursor (glucosamine) indicated that high
      molecular-weight mucin glycoprotein was synthesized by these immortalized cells,
      which reacted with the antiserum to the native CTM. Equilibrium gradient
      centrifugation analysis showed that the buoyant density of the mucin synthesized
      in CT1 cells (1.486 g/ml) was similar to the reported value for native CTM (1.5
      g/ml). Mucin which was isolated from immortalized cells was not a proteoglycan as
      chondroitinase treatment had no effect. These results suggest that CT1 cells
      synthesize a mucin glycoprotein which exhibits properties similar to native CTM.
      When characterized by immunostaining with a pool of monoclonal antibodies, these
      cells showed common epithelial antigens related to keratin expression. The CT1
      cell line represents a unique resource for studying mucin biosynthesis and
      regulation.

PMID- 7734846
TI  - Characterization of O-linked glycosylation motifs in the glycopeptide domain of
      bovine kappa-casein.
AB  - kappa-Casein is the major glycoprotein in bovine milk. It has a proteinase
      sensitive (chymosin) site which cleaves the glycoprotein into two segments: N
      terminal para-kappa-casein domain and the C-terminal kappa-casein
      macroglycopeptide domain which is highly heterogeneous in oligosaccharide
      content. We have identified six sites of O-glycosylation on the macroglycopeptide
      by solid-phase Edman degradation: Thr121, Thr131, Thr133, Thr136 (A variant
      only), Thr142 and Thr165. No Ser residues are glycosylated. The glycosylation
      status of 15 of 17 potential O-glycosylation sites in the B variant was
      accurately predicted using the four peptide motifis previously proposed for the
      glycosylation of human glycophorin A (Pisano, A., Redmond, J.W., Williams, K.L.
      and Gooley, A.A., Glycobiology, 3, 429-435, 1993), provided one additional
      assumption is made concerning an inhibitory role for a nearby Ile.

PMID- 7734847
TI  - Biosynthesis of lipophosphoglycan from Leishmania major: characterization of
      (beta 1-3)-galactosyltransferase(s).
AB  - Lipophosphoglycan (LPG) is the major cell surface molecule of promastigotes of
      all Leishmania species. It is comprised of three domains: a conserved GPI anchor
      linked to a repeating phosphorylated disaccharide (P2; PO4-6-Gal(beta 1
      4)Man(alpha 1-) backbone variously substituted with galactose, glucose and
      arabinose residues in L.major and capped with a neutral oligosaccharide. Using a
      microsomal membrane preparation from L.major, we have been able to demonstrate
      that galactose from UDP-[14C]galactose can be transferred to an endogenous
      acceptor, characterized as LPG. An in vitro assay was established, based on anion
      exchange HPLC, that concurrently identifies and quantitates the products of the
      galactosyltransferases. We show that the products formed are [14C]galactose
      labelled P3 (PO4-6-[Gal(beta 1-3)]Gal(beta 1-4)Man(alpha 1-), P4b (PO4-6
      [Gal(beta 1-3)Gal(beta 1-3)]Gal(beta 1-4)Man(alpha 1-) and P5b(PO4-6-[Gal(beta 1
      3)Gal(beta 1-3)Gal(beta 1-3)]Gal(beta 1- 4)Man(alpha 1-). These are major
      galactosylated repeating units of the backbone of L.major LPG. The same products
      are also formed when LPG from L.donovani, which contains an unbranched backbone
      of P2 repeats, is used as an exogenous acceptor with L.major microsomal membranes
      and UDP-[14C]galactose. In addition, no formation of radioactive backbone repeats
      (P2) was detected in membrane incubations containing UDP-[14C]galactose with or
      without added unlabelled GDP-mannose, indicating that the addition of the (beta 1
      3)-linked galactose branches is independent of the synthesis of the repeating
      disaccharide (P2) backbone. Preliminary kinetic analyses suggest that the
      addition of multiple (beta 1-3)-linked galactose residues may be catalysed by
      more than one (beta 1-3) galactosyltransferase. The (beta 1
      3)galactosyltransferase(s) activity was not detected in microsomal membrane
      preparations from promastigotes of L.donovani.

PMID- 7734848
TI  - Immunohistochemical localization of minor gangliosides in the rat central nervous
      system.
AB  - We previously described the differential distribution of major gangliosides (GM1,
      GD1a, GD1b, GT1b and GQ1b) in adult rat brain detected by specific antibodies
      (Kotani, M., Kawashima, I., Ozawa, I., Terashima, T. and Tai, T. Glycobiology, 3,
      137-146, 1993). We report here the distribution of minor gangliosides in the
      adult rat brain by an immunofluorescence technique with mouse monoclonal
      antibodies (MAbs). Ten MAbs (GMR6, GMB28, GMR11, GMR19, GMR2, GMR7, GGR51, AMR10,
      NGR54 and NGR53) that specifically recognize GM3, GM2, GT1a, GD3, O
      Acdisialoganglioside, GD2, GM1b, GM4, IV3NeuAc alpha-nLc4Cer and IV6NeuAc alpha
      nLc4Cer, respectively, were used. Our study revealed that there is a cell type
      specific expression of minor gangliosides, as well as major gangliosides, in the
      rat brain. In the cerebellar cortex, GM3 was expressed intensely in the white
      matter and slightly in the granular layer. GD3 was present in both the granular
      layer and the white matter, but not in the Purkinje cell layer or in the
      molecular layer. An O-Ac-disialoganglioside, which was suggested to be O-Ac-LD1,
      was detected exclusively in both the molecular layer and Purkinje cell layer. The
      presence of GD2 was restricted to the granular layer. GM4 was associated with
      some astrocytes, but not with myelin or oligodendrocytes. GM2, GT1a, GM1b,
      IV3NeuAc alpha-nLc4Cer and IV6NeuAc alpha-nLc4Cer gangliosides were not clearly
      detected in the cerebellar cortex. In other regions, such as cerebral cortex,
      hippocampal formation and spinal cord, the expression of the gangliosides was
      also highly localized to a specific cell type and layer.

PMID- 7734849
TI  - Expression of N-acetylglucosaminyltransferase V mRNA in mammalian tissues and
      cell lines.
AB  - The expression of N-acetylglucosaminyltransferase V (Glc-NAc-T V) is increased in
      many oncogenically transformed cells and in cell lines which are induced to
      proliferate. In order to characterize the regulation of GlcNAc-T V at the
      molecular level, we have examined the expression of Glc-NAc-T V mRNAs in a number
      of mouse tissues and in several human and rodent cell lines. The GlcNAc-T V mRNA
      is expressed in different amounts in the various mouse tissues, with the greatest
      amount observed in brain, followed by thymus, kidney, lung, intestine, heart and
      stomach, and no transcripts detected in liver or skeletal muscle. Measurements of
      GlcNAc-T V enzymatic activity, by contrast, show brain to have lower levels of
      activity than several of the other tissues, suggesting possible post
      translational regulation. We find that there are two GlcNAc-T V transcripts in
      most of the RNAs analysed. The rodent cell lines all express both a 7.5 and a 9.5
      kb mRNA, with the smaller transcript being more abundant. The human cells have
      mRNAs of 4.5 and 9.5 kb. Both mRNAs are expressed in HepG2 and MCF-7 cells, while
      A431 cells express only the 4.5 kb mRNA and HL60 cells express only the 9.5 kb
      transcript. Furthermore, only the 9.5 kb mRNA appears to be increased, along with
      activity, when HepG2 cells are stimulated to proliferate, suggesting that the two
      mRNAs may be under different regulatory controls. Also, a GlcNAc-T V-deficient,
      mutant lymphoma cell line, PHAR2.1, was found to express mRNAs which are larger
      than the normal mRNAs, possible due to an insertion or aberrant splicing,
      resulting in a defective mRNA.

PMID- 7734850
TI  - Alterations of O-glycan biosynthesis in human colon cancer tissues.
AB  - Human colon cancer is associated with antigenic and structural changes in mucin
      type carbohydrate chains (O-glycans). To elucidate the control of the
      biosynthesis of these O-glycans is colon cancer, we have studied
      glycosyltransferase and sulphotransferase activities involved in the assembly of
      elongated O-glycan structures. We analysed homogenates prepared from cancer
      tissue, adjacent normal and distal normal tissue from 20 patients. Several
      transferase activities showed pronounced changes in cancer tissue. The changes
      correlate with previous findings of a loss of O-glycans in cancer mucins, but did
      not always correlate with levels of Tn, sialyl-Tn, T and Lex antigens in
      homogenates or with the differentiation status and Duke's stages of the cancer
      tissue or the patient's blood type, sex and age. UDP-GlcNAc: Gal NAc-R beta 3-N
      acetylglucosaminyltransferase (where GlcNAc is N-acetyl-D-glucosamine and GalNAc
      is N-acetyl-D-galactosamine) synthesizing O-glycan core 3, GlcNAc beta 1-3GalNAc
      , CMP-sialic acid: GalNAc-peptide alpha 6-sialyltransferase synthesizing the
      sialyl-Tn antigen and sulphotransferase activities towards O-glycan core 1, Gal
      beta 1-3GalNAc-, were found to be decreased in cancer. UDP-GlcNAc: Gal beta 1
      3GalNAc beta 6-N-acetylglucosaminyltransferase was also decreased in cancer
      concomitant with a loss of the ability to synthesize the I antigen and core 4,
      GlcNAc beta 1-6(GlcNAc beta 1-3) GalNAc-, CMP-sialic acid: Gal beta 1-3GalNAc-R
      alpha 3-sialyltransferase and GDP-fucose: Gal beta-R alpha 2-fucosyltransferase,
      synthesizing the blood group H determinant, were found to be 4- and 3- to 8-fold
      increased, respectively, in cancer compared to normal tissue. The data suggest
      that the biosynthesis of antigens and mucin-bound O-glycan structures in colon
      cancer is subject to complex control mechanisms.

PMID- 7734851
TI  - Core fucosylation of high-mannose-type oligosaccharides in GlcNAc transferase I
      deficient (Lec1) CHO cells.
AB  - During studies on the fucosylation of endogenous proteins in parental (Pro5) and
      N-acetyl-D-glucosamine (GlcNAc) transferase I-deficient (Lec1) Chinese hamster
      ovary (CHO) cells, we observed that Lec1 cells incorporate approximately 10-fold
      less [3H]fucose into macromolecules than Pro5 cells. Interestingly, most of the
      labelled oligosaccharides from both cell types could be released from the
      macromolecules by digestion with peptide N-glycosidase F (PNGase F). This was
      unexpected for Lec1 cells because they do not synthesize complex- or hybrid-type
      N-glycans. Structural analyses of the fucosylated oligosaccharides from Lec1
      cells showed the fucose to be in an alpha 1,6 linkage to the core GlcNAc of
      relatively small oligomannose N-glycans (Man4GlcNAc2 and Man5GlcNAc2, where Man
      is D-mannose). Comparing the sizes of oligomannose N-glycans from Pro5 and Lec1
      cells demonstrated a much higher proportion of the small (Man4GlcNAc2 and
      Man5GlcNAc2) oligomannose species in Lec1 cells. These results suggest that the
      core alpha 1,6 fucosyltransferase will fucosylate small (Man4-Man5GlcNAc2), but
      not large (Man8-Man9GlcNAc2) oligomannose N-glycans.

PMID- 7734852
TI  - Polylactosamines are not obligate receptors for invasion of Plasmodium falciparum
      malaria as shown in HEMPAS variant II-gal- erythrocytes.
AB  - A HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum
      test) erythrocyte, atypical Variant II (referred to herein as Variant II-gal-),
      lacking long-chain polylactosamine on both glycoproteins (Band 3 and 4.5) and
      glycosphingolipids, was characterized by the carbohydrate profile of the
      erythrocyte membrane according to Fukuda et al. (Blood, 73, 1331-1339, 1989). Two
      laboratories previously reported that polylactosamine isolated from the
      erythrocyte protein Band 3 inhibited invasion of red blood cells by Plasmodium
      falciparum in malarial culture, suggesting a role for this carbohydrate in
      adhesion of the parasite. Therefore, HEMPAS erythrocyte Variant II-gal- presented
      a unique opportunity to further examine this premise. Freshly drawn blood samples
      (normal and HEMPAS Variant II-gal-) were separately incubated with P. falciparum
      from mannitol-synchronized cultures. The parasite was found to invade HEMPAS
      Variant II-gal- erythrocytes at a 30% lower rate through two life cycles, as
      shown by microscopic evaluation of invasion and by [3H]hypoxanthine incorporation
      into parasite. This observation, along with the published fact that glycophorin
      deficient MkMk cells are also infectable, but at a lower rate, indicates that
      neither sialoglycoproteins nor polylactosamines are an obligate adhesive ligand
      for P. falciparum, although the possibility remains that either may still
      contribute to adhesive events during infection.

PMID- 7734853
TI  - Mannolipid donor specificity of glycosylphosphatidylinositol mannosyltransferase
      I (GPIMT-I) determined with an assay system utilizing mutant CHO-K1 cells.
AB  - The microsomal enzyme glycosylphosphatidylinositol mannosyltransferase I (GPIMT
      I) catalyses the transfer of a mannosyl residue from beta
      mannosylphosphoryldolichol (beta-Man-P-Dol) to glucosamine
      alpha(1,6)(acyl)phosphatidylinositol (GlcN-aPI) to form Man alpha(1,4)GlcN-aPI
      (ManGlcN-aPI), an intermediate in glycosylphosphatidylinositol (GPI) synthesis.
      While the transfer of [3H]mannosyl units to endogenous GlcN-aPI was not seen when
      membrane fractions from normal Chinese hamster ovary (CHO) K1 cells were
      incubated with exogenous [3H]Man-P-Dol, GPIMT-I activity could be characterized
      with an in vitro enzyme assay system employing membrane fractions from Lec15 or
      Lec35 cells. These CHO cell mutants apparently contain elevated levels of
      endogenous GlcN-aPI due to the inability to synthesize (Lec15) or utilize (Lec35)
      beta-Man-P-Dol in vivo. The presence of a saturated alpha-isoprene unit in the
      dolichyl moiety is required for optimal GPIMT-I activity since beta
      mannosylphosphorylpolyprenol (beta-Man-P-Poly), which contains a fully
      unsaturated polyisoprenyl chain, was only 50% as effective as beta-[3H]Man-P-Dol
      as a mannosyl donor. When beta-[3H]-Man-P-Dol and alpha-[3H]Man-P-Dol were
      compared as substrates, GPIMT-I exhibited a strict stereospecificity for the
      mannolipid containing the beta-mannosyl-phosphoryl linkage. beta-[3H]Man-P
      dolichols containing 11 or 19 isoprenyl units were equally effective substrates
      for GPIMT-I. Membrane fractions from Lec 9, a CHO mutant that apparently lacks
      polyprenol reductase activity and synthesizes very little beta-Man-P-Dol, but
      accumulates beta-Man-P-Poly, synthesized no detectable Man-GlcN-aPI when
      incubated with beta-[3H]Man-P-Dol in vitro. This indirect assay suggests that
      GlcN-aPI does not accumulate in Lec 9 cells, possibly because it is mannosylated
      via beta-Man-P-Poly, or perhaps the small amount of Man-P-Dol formed by the
      mutant in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7734854
TI  - Post-translational modifications distinguish cell surface from Golgi-retained
      beta 1,4 galactosyltransferase molecules. Golgi localization involves active
      retention.
AB  - beta 1,4 Galactosyltransferase (GalT) is a membrane-bound enzyme localized
      predominantly to the trans-Golgi cisternae. Our previous studies have shown that
      the transmembrane domain of bovine GalT plays a critical role in Golgi
      localization (Teasdale, R.D., D'Agostaro, G. and Gleeson, P.A., J. Biol. Chem.,
      267, 4084-4096, 1992). Here we have compared the localization and post
      translational modifications of full-length bovine GalT with a GalT/hybrid
      molecule where the transmembrane domain of GalT was replaced with that of the
      transferrin receptor. GalT/hybrid molecules were expressed on the surface of
      transfected cells; however, differences were observed in the distribution of the
      hybrid molecules between transfected COS and murine L cells. In transfected COS
      cells, the GalT/hybrid protein was expressed efficiently at the cell surface,
      with little Golgi-localized material, whereas in stable murine L cells, which
      expressed lower levels of the construct, hybrid molecules were detected both at
      the cell surface and within the Golgi apparatus. Expression of the GalT
      constructs in either COS or L cells produced two glycoprotein products which
      differed in molecular mass by 7 kDa. The difference in size between the two
      products is due to post-translational modifications which are inhibited by
      brefeldin A and are therefore likely to occur in the trans-Golgi network (TGN).
      Very little of the high-molecular-weight species was detected for full-length
      GalT, whereas it was a major product for the GalT/hybrid protein. Only the higher
      molecular weight species was expressed at the cell surface. Thus, this additional
      7 kDa post-translational modification distinguishes molecules retained within the
      Golgi apparatus (lower M(r) species) from those transported through the TGN to
      the cell surface. These studies indicate that (i) the level of expression
      influences the intracellular distribution of GalT/hybrid molecules and (ii) the
      localization of full-length GalT involves active retention within the Golgi
      stack, and not retrieval from later compartments. After treatment of membrane
      preparations from stable L cell clones with a heterobifunctional cross-linking
      agent, full-length bovine GalT molecules were found almost exclusively as high
      molecular-weight aggregates, suggesting that GalT exists as an oligomer or
      aggregate. This ability to oligomerize may be a requirement for Golgi retention.

PMID- 7734855
TI  - Chaos: a potential problem in the biological control of insect pests.
AB  - Erratic variations are normally observed in the populations of insect pests that
      destroy crop plants. To establish a scientific basis for developing effective
      control procedures, we have developed a model system for the European Corn Borer
      (ECB) (Ostrinia nubilalis) for which extensive field data, as well as laboratory
      results, have been accumulated during the past four decades. The model includes
      both a natural ECB pathogen and a genetically engineered toxin-producing agent as
      possible means of biological control. Our aim was to determine the conditions
      that could cause the population to vary erratically, as observed in the field.
      The erratic behavior in our simulations was analyzed to determine whether it is
      chaotic; chaos is a distinct type of erratic behavior which shows extreme
      sensitivity to initial conditions, i.e., the starting size of the population. Our
      simulations show that an increase in the death rate of the infected ECB, or a
      decrease in the birth rate of uninfected ECBs from infected ones, variables that
      are known to be affected by weather conditions, can induce a chaotic regime in
      which ECB population peaks reach values far higher than before chaos set in.
      Population peaks are even greater in the presence of both biological control
      agents. The results show that a biological control regime cannot be effective
      under conditions that induce chaotic population dynamics. Microcosm studies could
      be used to determine whether this situation would occur in the field.

PMID- 7734856
TI  - Transient behavior of biological loop models with application to the Droop model.
AB  - In this paper we study the transient behavior of a class of nonlinear
      differential systems verifying sign conditions through the succession of extrema
      of the state variables. This analysis does not depend, for the main part, on the
      analytical formulation of the model. The possible scenarios of sequences for the
      extrema, are represented on a graph and can be compared with the experimental
      data to validate the model. An application to the Droop model illustrates this
      method; we obtain as a result the global stability of the equilibrium and the
      possible successions of the extrema.

PMID- 7734857
TI  - Models for the effects of individual size and spatial scale on competition
      between species in heterogeneous environments.
AB  - A spatially explicit model for competition with dispersal in a heterogeneous
      environment is used to study the effects of individual size and the spatial scale
      of the environment on the competitive interactions between species. The model is
      a Lotka-Volterra competition system with diffusion and with spatial variation in
      some coefficients. The coefficients in the model are taken to reflect a situation
      where the larger competitor typically disperses farther in unit time than the
      smaller and reproduces less rapidly, but has an advantage in contests or other
      forms of interference competition. The environment is assumed to be closed, i.e.,
      it is assumed that individuals do not leave through the boundary. The environment
      is generally assumed to consist of a patch of favorable habitat surrounded by
      less favorable regions. The effects of spatial scale are studied by examining how
      the predictions of the model change as the size of the favorable patch is varied.
      The predictions turn out to be in qualitative agreement with the results of some
      empirical studies.

PMID- 7734858
TI  - Unrooted genealogical tree probabilities in the infinitely-many-sites model.
AB  - The infinitely-many-sites process is often used to model the sequence variability
      observed in samples of DNA sequences. Despite its popularity, the sampling theory
      of the process is rather poorly understood. We describe the tree structure
      underlying the model and show how this may be used to compute the probability of
      a sample of sequences. We show how to produce the unrooted genealogy from a set
      of sites in which the ancestral labeling is unknown and from this the
      corresponding rooted genealogies. We derive recursions for the probability of the
      configuration of sequences (equivalently, of trees) in both the rooted and
      unrooted cases. We give a computational method based on Monte Carlo recursion
      that provides approximates to sampling probabilities for samples of any size.
      Among several applications, this algorithm may be used to find maximum likelihood
      estimators of the substitution rate, both when the ancestral labeling of sites is
      known and when it is unknown.

PMID- 7734859
TI  - Computational methods for Markov series with large state spaces, with application
      to AIDS modeling.
AB  - AIDS models, and epidemiological models generally, are almost exclusively either
      differential equations or Markov processes. Of course, the phenomena are
      fundamentally random, so at best differential equations track the expectation of
      the process and variability is masked. There are few techniques in the literature
      for numerical analysis of Markov chains of any size, and so those wishing to
      analyze stochastic epidemics presently have little alternative to simulation. The
      contribution of the present paper is to propose numerical techniques capable of
      finding marginal probabilities of Markov chains having thousands and even
      millions of states. The ideas are illustrated by application to AIDS models in
      the literature which formerly had been investigated only through Monte Carlo.
      This introductory foray has not plumbed the depths of the computational
      methodology, which yet needs refinement and streamlining that comes through
      experience. Yet in its primitive form, it is shown herein to be adequate for a
      computation on the scale of a two-population partition of the San Francisco
      homosexual epidemic. The closing discussion compares the strengths and weaknesses
      of the present numerical techniques with the simulation approach to investigation
      of Markov epidemics.

PMID- 7734860
TI  - Low neonatal cerebral oxygen delivery is associated with brain injury in preterm
      infants.
AB  - Neonatal cerebral oxygen delivery was estimated in 93 preterm infants
      (gestational age < 34 weeks) who survived the neonatal period. Of these, 26 had
      developed neurological handicap at follow-up 1.7-4.6 years later. Neonatal
      cerebral oxygen delivery was dependent on gestational age, and was also related
      to the degree of intra-uterine growth retardation, carbon dioxide tension, and
      blood glucose concentration. Lower oxygen delivery was observed in infants who
      developed germinal layer haemorrhage or periventricular leucomalacia compared
      with infants with normal brains. However, as no information on cerebral metabolic
      demand or oxygen extraction is available, it is unclear whether decreased oxygen
      delivery is a contributing factor to brain damage or whether it is a marker of
      existing injury.

PMID- 7734861
TI  - Dosing considerations for oral acyclovir following neonatal herpes disease.
AB  - Herpes simplex virus lesions recur in 8-30% of infants who receive a course of
      parenteral antiviral therapy for an initial infection. Long-term acyclovir is
      used by some clinicians to prevent recurrent Herpes simplex disease. We describe
      nine infants who were treated with doses of oral acyclovir which were chosen to
      achieve 2-h post-plasma concentrations of > or = 2 micrograms/ml. Eight infants
      had Herpes simplex encephalitis and one had multiple recurrences of dermal and
      ocular disease. The target plasma concentration was chosen in order to attain
      acyclovir cerebrospinal fluid distribution (< or = 50% plasma) for an estimated
      ID30 of Herpes simplex II strains of 0.1-0.5 microgram/ml. One of nine patients
      failed to achieve the target plasma acyclovir concentration. One of nine patients
      developed symptomatic recurrence of the central nervous system disease and none
      of the remaining eight patients experienced recognized dermal or neurologic
      recurrence of Herpes simplex disease. Renal and neurologic status were routinely
      monitored and no signs of acyclovir toxicity were observed. Plasma concentration
      of acyclovir > or = 2 micrograms/ml may be achieved with average oral doses of
      1340 mg/m2/dose (1000-1740 mg/m2/dose) given at 12-h intervals.

PMID- 7734862
TI  - Outcome of extremely low-birth-weight infants: 1980-1990.
AB  - Neonatal and follow-up data of infants from the special care nursery whose birth
      weights were < 750 g, born between 1980 and 1990, were reviewed. There was a 20%
      relative improvement in the odds of surviving the neonatal period, a 16%
      improvement in the odds of being discharged and a 19% improvement in the odds of
      surviving until 2 years of age with each consecutive year. Home oxygen use
      increased significantly over the study period. The neurodevelopmental outcomes of
      infants were similar over the 11-year period, with 53% being classified as
      neurologically normal, with a mean developmental index of 83 at 1 to 2 years of
      age. We conclude that there has been an improved survival of infants with birth
      weights < 750 g in our institution, and that the overall incidence of serious
      neurodevelopmental deficits among survivors has remained stable.

PMID- 7734863
TI  - Seasonality in lower leg length velocity in prepubertal children.
AB  - Despite low measuring error, annual growth is poorly predicted by short-term
      measurements of the lower leg. In order to study if this low correlation can be
      explained by seasonal changes in lower leg length (LLL) velocity, we followed
      short-term growth longitudinally in 50 prepubertal children with normal height
      and growth velocities. Height measurements were performed at 4-week intervals and
      LLL measurements at 1-2 week intervals. Analysis of annual growth showed
      seasonality in the monthly mean height velocity values: 5.06 (SD 5.02) cm/year
      during the autumn and 8.15 (SD 5.22) cm/year in the spring. Similarly, the
      monthly mean LLL velocity values changed from 1.80 (SD 1.07) cm/year in the
      autumn to 2.63 (SD 0.92) cm/year in the spring. The correlation between monthly
      LLL and annual height velocity was low (r = 0.27). The technical error of the LLL
      measurement was 7-8% of the mean monthly LLL velocity, while the mean values
      changed by 31% over the seasons. The annual height velocity was virtually
      independent of the variation in growth rate over the seasons. It is concluded
      that there is significant seasonality both in height and LLL velocity and that it
      takes place at the same time for both measures. Seasonality in LLL has not been
      reported previously and must be considered when studying short-term growth, for
      example when LLL is used for prediction of annual height velocity or when a short
      term treatment effect is examined using LLL.

PMID- 7734865
TI  - Lipoprotein (a) levels in children and young adults: the influence of physical
      activity. The Cardiovascular Risk in Young Finns Study.
AB  - A high lipoprotein(a) (Lp(a)) level is an independent and predominantly
      genetically determined risk factor for coronary heart disease and other vascular
      diseases. We studied the levels of Lp(a) and the influence of physical activity
      on Lp(a) in the young Finnish population. The study cohort comprised children and
      young adults aged 9, 12, 15, 18, 21 and 24 years (n = 2464) participating in a
      large multicenter follow-up study of cardiovascular risk factors in children and
      young adults. Data were available on physical activity, anthropometric variables,
      serum Lp(a), insulin and lipid levels. A physical activity index was calculated
      based on several physical activity variables. Lp(a) was determined by
      radioimmunoassay with a detection threshold of 3 mg/dl. Differences were assessed
      with non-parametric statistical analyses. The observed range of Lp(a) was from <
      3 to 90.8 mg/dl. The distribution of Lp(a) was highly skewed as 88% of the
      population (89% males and 87% females) had Lp(a) concentrations less than 25
      mg/dl. A total of 35% of the subjects had Lp(a) levels less than 3 mg/dl. There
      were no significant differences in Lp(a) levels with respect to age or gender.
      The serum concentration of Lp(a) was statistically significantly correlated with
      the level of physical activity. Other behavioral variables studied did not have a
      significant contribution to the variability of Lp(a) levels. These results
      demonstrate that levels of Lp(a) are not related to age, gender or many of the
      known coronary heart disease risk factors. However, physical activity is
      associated with favorable Lp(a) levels, as high levels of Lp(a) (> 25 mg/dl) were
      less frequent in the physically most active subjects.

PMID- 7734864
TI  - Peak expiratory flow rate in healthy children aged 6-17 years.
AB  - Peak expiratory flow rate (PEFR) was measured in a cross-sectional study in 861
      healthy Danish schoolchildren aged 6-17 years using a Mini Wright peak flowmeter.
      We found a strong correlation between PEFR and height, age and sex. The results
      were comparable with those from previous studies using a Wright peak flowmeter.
      The equation for prediction of PEFR in boys was calculated as (3.8 x height) +
      (10.6 x age) - 313.2 (p < 0.0001, r = 0.8), and for girls, PEFR = (2.2 x height)
      + (14.2 x age) - 143.9 (p < 0.0001, r = 0.64). Our results appear to be reliable,
      as evidenced by the high correlation coefficient in this large sample. Among
      healthy children without previous asthma, earlier episodes of recurrent wheezing
      were reported in 8.8% and a significantly lower PEFR was found in this group.

PMID- 7734866
TI  - Patient-triggered ventilation fooled by patency of ductus arteriosus.

PMID- 7734867
TI  - Gut intraepithelial lymphocyte counts in neonates, infants and children.
AB  - Intraepithelial lymphocyte (IEL) counts were histologically assessed in the
      jejunum, ileum and appendix of 39 neonates (0-28 days), 32 infants (1-9 months)
      and 13 children (1-9 years). Small intestinal mucosa samples were obtained from
      73 autopsies, and from 8 surgical and 3 aspirative biopsies. IEL counts of
      specimens from the jejunum, ileum and appendix gave similar results in the same
      patient. The number of IEL counts was significantly lower in neonates for all
      three segments. The difference between infants and children was more marked in
      the jejunum than in the ileum, although this was not significant. In the
      appendix, there was no difference between the different age groups. Our results
      indicate that postnatal expansion of IEL occurs homogeneously along the gut after
      the neonatal period.

PMID- 7734868
TI  - Relationship of sweat electrolytes to apparent life-threatening events (ALTE): a
      case control study.
AB  - Twenty infants aged 25 days to 6 months who were consecutively investigated for
      apparent life-threatening events (ALTE) with negative results and 20 matched
      normal controls underwent an iontophoresis sweat test. A statistically
      significant elevated sweat potassium level (22.1 +/- 8.9 versus 12.4 +/- 6.5
      mol/l) was noted in the ALTE patients compared with the control group (p <
      0.001). No difference was found, however, between sweat sodium and chloride
      levels in the two groups. Na/K ratio in sweat was significantly different between
      the groups (p < 0.001). A between-groups discriminant analysis, using Na/K ratio
      as a discriminant variable, resulted in 80% accuracy in group assignment. A
      significant increase in sweat potassium concentration at night compared with day
      time was evident in ALTE patients. Elevated sweat potassium levels specifically
      characterized infants who experienced ALTE and may possibly indicate an
      underlying mechanism involving enhanced sympathetic activity.

PMID- 7734869
TI  - Coeliac disease, enamel defects and HLA typing.
AB  - The presence of dental enamel defects in coeliac disease and their relation to
      hypocalcaemia or a particular HLA class in 82 Italian children with coeliac
      disease was studied. Demarcated opacities or hypoplasia were detected in 23
      subjects (group 1) while minimal or no dental lesions were found in the remaining
      59 patients (group 2); in 189 normal controls, enamel lesions were significantly
      less frequent than in patients with coeliac disease (14.8% versus 28.0%; p <
      0.005). No statistically significant differences were found for age at diagnosis
      and calcium concentrations between groups 1 and 2. Regression analysis showed a
      correlation between age at diagnosis and number of teeth with enamel defects. In
      our patients, the presence of HLA DR3 antigen significantly increased the risk of
      dental lesions, while genotype DR5,7 seemed to protect against enamel defects. A
      logistic regression analysis of the variables age, serum calcium concentrations,
      number of affected teeth, type of enamel defect and DR antigens showed that only
      DR antigens discriminated coeliac disease patients with from those without enamel
      defects.

PMID- 7734870
TI  - Helicobacter pylori infection in children with recurrent abdominal pain.
AB  - Helicobacter pylori was cultured and Helicobacter-like organisms (HLO) were seen
      in 6 (16%) of 37 children with recurrent abdominal pain. Five children had
      concomitant histological inflammation, but none had endoscopic changes. All 6
      children demonstrated positive serology. Compared with the total group, they were
      more often from developing countries, larger families and lower social groups.
      Treatment with phenoxymethyl penicillin and colloidal bismuth subcitrate did not
      result in side effects or elevated serum levels of serum bismuth. Three children
      demonstrated metronidazole-resistant strains and the treatment of these children
      remained an unsolved problem. Among the 31 H. pylori/HLO negative children 8
      (26%) demonstrated histological changes, 5 (16%) endoscopic changes and 11 (35%)
      had positive serology. In conclusion, pathological findings at upper
      gastrointestinal endoscopy are common in children with recurrent abdominal pain.
      Because of disconcordance between endoscopy, histology and culture, we recommend
      that biopsies should always be taken to clarify the diagnosis.

PMID- 7734872
TI  - Normal final height after treatment for acute lymphoblastic leukemia without
      irradiation.
AB  - In order to evaluate the influence of chemotherapy on linear growth, 28 children
      treated for acute lymphoblastic leukemia without irradiation were evaluated
      before, during and after the end of therapy. Median age at diagnosis was 4.4
      years (range 2.2-12.7 years) and treatment was discontinued after a median period
      of 3.1 years (3.0-5.2 years). We observed a significant decrease in height SDS (p
      = 0.006) from diagnosis to the end of chemotherapy, followed by catch-up in
      height SDS from the end of chemotherapy to final observation. Catch-up growth
      took place mainly within the first 2 years after cessation of therapy. In 22
      patients final height was reached. Final height was normal (median height SDS 
      0.035) and even significantly higher than mid-parental height SDS (p = 0.012). In
      those patients who attained adult stature, the sitting height to standing height
      ratio was also normal. In conclusion, in children treated for acute lymphoblastic
      leukemia, chemotherapy exerted a negative influence on growth, but catch-up
      occurred within 2 years after cessation of therapy, resulting in normal final
      height and body proportions.

PMID- 7734871
TI  - Assessment of tubular reabsorption of sodium, glucose, phosphate and amino acids
      based on spot urine samples.
AB  - Reference values for tubular transport of sodium, phosphate, glucose and amino
      acids are generally based on inulin or creatinine short-term clearances, which
      are difficult to obtain in children. Hence, quantitative assessment of tubular
      transport capacities is rarely performed. For a simplified procedure, reference
      values for fractional sodium excretion, phosphate reabsorption related to
      glomerular filtration rate, percent glucose and percent amino acid reabsorption
      were established in 62 children from spot urine and simultaneously obtained blood
      samples. Sodium excretion, and glucose and amino acid reabsorption were
      significantly lower in infants than children, whereas phosphate reabsorption
      decreased during the first year of life. Results using the proposed protocol and
      those obtained from timed urine specimens correlated well; the phenomenon of
      renal adaptation during childhood could equally well be demonstrated. Renal
      tubular dysfunction can be diagnosed without timed urine specimens.

PMID- 7734873
TI  - Brainstem auditory evoked potentials during hypoglycaemia in insulin-dependent
      diabetic children.
AB  - Brainstem auditory evoked potentials (BAEP) were studied in 10 type 1 diabetic
      children during normoglycaemia (5.5 +/- 0.4 mmol/l), hypoglycaemia and in the
      post-hypoglycaemic state. In addition, BAEP during normoglycaemia in diabetic
      children were compared with those of an age-, weight- and sex-matched group of
      healthy control children. No significant differences were observed between all
      latencies of the diabetic children compared with those of the healthy children
      during normoglycaemia. During induction of hypoglycaemia a minor (p < 0.05)
      prolongation of the inter-peak latency I-V at a blood glucose concentration of
      4.1 +/- 0.5 mmol/l was observed. This prolongation was not aggravated at glucose
      nadir (1.7 +/- 0.3 mmol/l). In conclusion, and in contrast with previous findings
      in non-diabetic children and in adults with type 1 diabetes, no changes in BAEP
      were demonstrated during short-term severe hypoglycaemia in diabetic children and
      only minor transient changes were seen during the initial phase of a standardized
      induction of hypoglycaemia.

PMID- 7734874
TI  - Exercise capacity and blood pressure response in children and adolescents after
      renal transplantation.
AB  - Physical working capacity and cardiovascular response to graded exercise on a
      bicycle ergometer were investigated in 70 children and adolescents (33F, 37M)
      after renal transplantation. Results of static and dynamic lung function tests
      were within the normal range in all patients. Systolic blood pressure, heart
      rate, pulmonary ventilation and oxygen uptake increased with workload and
      returned to pre-exercise levels after 5 m of rest. During exercise, blood
      pressure values were within the normal range in almost all patients. The increase
      in heart rate and respiratory frequency was blunted in patients receiving beta
      blocking agents. Maximum workloads (Wmax) were 2.00 +/- 0.48 W/kg in females and
      2.38 +/- 0.54 W/kg in males, which are 78 +/- 18% and 84 +/- 18% of the normal
      values predicted for age. Maximum oxygen consumption (VO2max) was 23.2 +/- 5.8
      ml/min/kg in females and 28.3 +/- 5.8 ml/min/kg in males. Half of the patients
      had height below the third percentile. For this reason exercise capacity in
      relation to height is probably a more relevant parameter than age. Using actual
      height, Wmax was 102 +/- 20% and 102 +/- 29%, and VO2max 74 +/- 14% and 80 +/-
      18% of predicted values, respectively. We conclude that the adaption of the
      cardiovascular and respiratory system to graded exercise was influenced by beta
      blocking agents. Wmax and VO2max were significantly reduced for age in pediatric
      patients after renal transplantation. Wmax was normal, but VO2max was still
      reduced if corrected for height.

PMID- 7734875
TI  - Parent and teacher perceptions of child behaviour following cardiac surgery.
AB  - To determine if parents whose children had undergone successful cardiac surgery
      perceived their children any differently from parents of children who had not
      undergone surgery, we used the Achenbach Child Behaviour Checklist (CBCL) to
      compare parent and teacher perceptions in these two groups. Subjects included 168
      children who had undergone cardiac surgery 4 to 8 years previously and 51
      controls. On the behaviour scale of the CBCL, the teacher's mean t scores showed
      no significant difference between the cardiac and control groups, in contrast to
      the parents' scores where parents perceived a higher degree of behavioural
      problems in children who had undergone cardiac surgery. On the social competence
      scale of the CBCL, the parents scored their children who had undergone cardiac
      surgery as less socially competent than did the parents of the controls.
      Teachers' scores showed no difference between groups.

PMID- 7734876
TI  - Cord blood IGE versus family history as atopic predictors in the newborn.

PMID- 7734877
TI  - TNF production in children with humoral immunodeficiency.

PMID- 7734878
TI  - Unchanged MRI of myelin in adolescents with PKU supplied with non-phe essential
      amino acids after dietary relaxation.

PMID- 7734879
TI  - Primary non-Hodgkin's lymphoma of the skin in children.

PMID- 7734880
TI  - Poisoning with household chemicals in children.

PMID- 7734881
TI  - Acetazolamide without frusemide in the treatment of post-haemorrhagic
      hydrocephalus.

PMID- 7734882
TI  - Near-infrared interactance.

PMID- 7734883
TI  - Treatment of EBV-induced lymphoproliferative disorder with epipodophyllotoxin
      VP16-213.
AB  - A case of haemophagocytic lymphohistiocytosis consistent with X-linked
      lymphoproliferative disorder is described. Remission was observed after
      administration of VP-213, a cytotoxic drug generally used to treat histiocytosis.
      The child is currently in good clinical health.

PMID- 7734884
TI  - Endovascular treatment of a spinal arteriovenous malformation in a 21-month-old
      boy.
AB  - Reports of spinal arteriovenous malformations in children are rare. This case
      report describes a 21-month-old boy whose first symptom was attacks of abdominal
      pain, followed gradually by neurological symptoms. The diagnosis was made using
      magnetic resonance imaging and spinal angiography, and the patient was
      successfully treated with embolization.

PMID- 7734885
TI  - Myositis ossificans progressiva: a 10-year follow-up on a patient treated with
      etidronate disodium.
AB  - We describe a child who was treated for 10 years with etidronate disodium for
      myositis ossificans. There were no typical bouts of swelling, reddening or
      hardening of areas over the skeletal muscles with this treatment and there were
      no side effects. Nevertheless, a constant gradual progression of the disease led
      to severe limitation of joint movement. This is the first report on long-term
      treatment with etidronate disodium.

PMID- 7734886
TI  - Accuracy of anthropometric measurements in predicting symptomatic SGA and LGA
      neonates.
AB  - Mid-arm circumference, mid-arm circumference/head circumference ratio, ponderal
      index and skinfold thickness at five sites (biceps, triceps, quadriceps,
      subscapular and flank) were measured in 91 small-for-gestational-age (SGA) and
      101 large-for-gestational-age (LGA) neonates to investigate their accuracy in
      identifying neonates at high risk of complications resulting from disturbed
      intrauterine growth. Thirty-one of 91 SGA and 19 of 101 LGA neonates who
      developed hypoglycaemia and/or polycythaemia were regarded as symptomatic. Mean
      values of all of the anthropometric parameters differed significantly between
      symptomatic and asymptomatic SGA or LGA neonates. The quadriceps skinfold
      thickness was the most sensitive index in predicting symptomatic SGA and LGA
      neonates (sensitivity 0.93 and 0.95, respectively). The mid-arm circumference was
      also a very sensitive index in predicting symptomatic SGA neonates (sensitivity
      0.94) but its specificity was extremely low (0.20). The rest of the parameters
      showed lower sensitivity than quadriceps skinfold thickness associated with
      similarly low specificity and validity. The findings of this study indicate that
      the quadriceps skinfold thickness is the most reliable index for use as a
      screening test for clinical evaluation of SGA and LGA neonates who are likely to
      develop complications as a result of disturbed intrauterine nutrition.

PMID- 7734887
TI  - The usefulness of serial C-reactive protein measurement in managing neonatal
      infection.
AB  - Recent advances in laboratory technology have enabled us to measure C-reactive
      protein with a higher sensitivity in a short period using a minimal amount of
      blood. Thus C-reactive protein can be measured easily several times a day. In
      this study, serial changes in C-reactive protein values were evaluated in 108
      term and 240 preterm newborn infants with suspicion of infection, and the
      changing patterns of C-reactive protein values were compared with clinical
      outcome. For a diagnosis of infection, the negative predictive values in term and
      preterm infants were 99.0% and 97.8%, respectively, although the sensitivities
      were 61.5% and 75.0%, respectively. Antibiotic therapy was started at birth and
      discontinued when the changing pattern of C-reactive protein and clinical
      findings did not suggest infection. As a result, mean durations of administration
      of antibiotics in the term and preterm infants were 3 and 4 days, respectively.
      Recognition of the changing pattern of C-reactive protein was very useful in
      excluding infection and minimizing unnecessary antibiotic therapy in managing
      neonatal infection.

PMID- 7734888
TI  - Treatment of respiratory failure in an infant with bronchopulmonary dysplasia
      infected with respiratory syncytial virus using inhaled nitric oxide and high
      frequency ventilation.
AB  - A 2-month-old, former 28-week premature infant with bronchopulmonary dysplasia
      infected with respiratory syncytial virus was treated with nitric oxide and high
      frequency oscillatory ventilation after conventional therapy failed. Nitric oxide
      and high frequency oscillatory ventilation rapidly improved oxygenation allowing
      recovery without the need for extracorporeal membrane oxygenation. This treatment
      regimen should be considered as an option in high-risk infants with respiratory
      syncytial virus infection who meet extracorporeal membrane oxygenation criteria.

PMID- 7734889
TI  - Metabolic alkalosis due to the use of an oligoantigenic diet in infancy.
AB  - A 7-month-old boy on an oligoantigenic diet because of multiple food intolerances
      presented with anorexia, failure to gain weight and severe hypochloremic
      metabolic alkalosis with hyperreninemia. Clinical symptoms and biochemical
      abnormalities disappeared after adequate dietary supplementation with potassium
      and sodium chloride. This case emphasizes that minimal daily mineral requirements
      must be provided in infant diets, and highlights the risk of nutritional
      deficiencies inherent in the prolonged use of oligoantigenic diets not adequately
      supplemented.

PMID- 7734890
TI  - Congestive heart failure caused by vitamin D deficiency?
AB  - We describe a child, 3.5 months old, with severe vitamin D deficiency, profound
      hypocalcaemia, hyperphosphataemia, dilated left ventricle, severely reduced
      myocardial contractility and congestive heart failure. She also had depressed
      thyroid function with subnormal thyroxine and non-detectable serum thyrotropin
      (TSH) levels. The child promptly responded to calcium infusions, conventional
      anticongestive therapy and calcitriol. She is now 3 years old and received no
      medication. Myocardial function is normal but she has motor delay. We believe
      that her transitory congestive heart failure was caused by severe vitamin D
      deficiency with profound hypocalcaemia.

PMID- 7734891
TI  - Surfactant replacement therapy in neonates with respiratory failure due to
      bacterial sepsis.
AB  - We describe four newborns (gestational ages 29-37 weeks; birthweights 1380-3040
      grams) who were mechanically ventilated for respiratory insufficiency because of
      bacterial sepsis. A beneficial effect of bovine surfactant (Alvofact, dosages 50
      or 100 mg/kg) was found, as shown by decreases in mean airway pressures and
      oxygen demands. No side effects were seen after instillation.

PMID- 7734892
TI  - Does a family history of atopy influence lung function at follow-up of infants
      born prematurely?
AB  - The aim of this study was to assess whether a family history of atopy influenced
      lung function at follow-up of infants born prematurely. Analysis was made of
      thoracic gas volume and airways resistance measurements performed at 1 year of
      age in 86 infants born at a median gestational age of 29 weeks. These
      measurements had been made during a prospective follow-up study. The 30 infants
      with a family history of atopy were found to have a higher airways resistance
      (median 35 cmH2O/l/s) than the 56 infants without such a family history (median
      30 cmH2O/l/s) (p < 0.05). However, when the results from 18 infants with a family
      history of atopy were compared with 18 controls who were matched for requirement
      for neonatal ventilation, parental smoking and were within at least 1 week of
      gestational age, no significant difference in airways resistance was found
      between the two groups. Multiple regression analysis demonstrated that
      gestational age and birth weight explained the apparent relationship between a
      family history of atopy and an elevated airways resistance at follow-up.

PMID- 7734893
TI  - Necrotizing enterocolitis prophylaxis.

PMID- 7734894
TI  - Relationships between physical growth, mental development and nutritional
      supplementation in stunted children: the Jamaican study.
AB  - The relationship between physical growth and change in mental development on the
      Griffiths mental development scales was investigated in 127 stunted Jamaican
      children over a 2-year period. The role of nutritional supplementation in this
      relationship was examined. There were no consistent associations between changes
      in weight-for-height or head circumference and developmental change. Height gain
      over 2 years was significantly associated with change in mental age, and
      locomotor and hearing and speech subscale scores. Height gain in the first year
      predicted change in mental age, and hearing and speech in the second year. Some
      of the effect of supplementation on development was shared with linear growth.
      Therefore, nutrition probably explains part of the relationship between growth
      and development. However, supplementation also had effects on development
      independent of growth. The benefits of supplementation on development and the
      extent to which they were shared with growth varied among the subscales.

PMID- 7734895
TI  - Screening for minimal brain dysfunction (MBD/DAMP) at six years of age: results
      of motor test in relation to perinatal conditions, development and family
      situation.
AB  - The aim of this study was to investigate if children aged 6 years of age,
      classified as having minimal brain dysfunction (MBD) or deficit in attention,
      motor control and perception (DAMP), exhibit special medical problems, specific
      developmental features or if special psychosocial conditions exist in the family.
      The screening program, using the psychoneurological part of the method developed
      by Gillberg et al., included 234 children who were followed-up prospectively from
      pregnancy and birth. The results were related to the physical and mental
      development of the children, to the psychosocial and socioeconomic conditions of
      the families, to pre- and postnatal conditions and to "reduced optimality score",
      as defined by Prechtl. Mental development was assessed by the use of Griffiths'
      test at 10-14 months and at 4-5 years of age. At the second Griffiths' test, the
      mother was also interviewed about the presence of aggressiveness and other
      symptoms of childhood psychopathology in her child, as defined by the DSM-III
      criteria, and a psychological observation was also made. In addition to screening
      for MBD/DAMP, at 6 years of age the parents were asked to complete a
      questionnaire aimed at identifying attention deficit disorder (ADD). No medical
      or psychological intervention was made before this stage. Fourteen children (9M,
      5F) (6%) were identified as having a positive MBD/DAMP screening result. The
      results of the screening procedure showed a weak correlation with those obtained
      using the questionnaire based on the DSM-III criteria for ADD.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7734896
TI  - Social and behavioural perspectives in enuretics, former enuretics and non
      enuretic controls.
AB  - Social and behavioural traits in children with primary nocturnal enuresis were
      compared with children who had outgrown their enuresis and children who had never
      bed-wetted after three years of age. The study group included 14 children with
      primary nocturnal enuresis, 15 children who had had primary nocturnal enuresis
      and 15 age- and sex-matched controls. The mothers of all children were
      interviewed using a 32-item questionnaire. If primary nocturnal enuresis were a
      neurotic disease, we would have expected a higher frequency of emotional
      dysfunction in children with enuresis and an increase in the symptoms or symptom
      substitution when bed-wetting was resolved. No significant differences in
      emotional or behavioural traits among the three groups were found. We conclude
      that children with primary nocturnal enuresis were well adjusted individuals and
      display similar social and behavioural traits as their peers. This study lends
      further support to the theory that primary nocturnal enuresis is not a
      psychological disorder.

PMID- 7734897
TI  - Short-term and long-term initial stay in hospital of children with insulin
      dependent diabetes: adjustment of families after two years.
AB  - A randomized prospective trial on the effect of the length of initial hospital
      stay (23 +/- 4 days and 9 +/- 3 days) in 61 consecutive children with newly
      diagnosed diabetes was carried out. Since the metabolic outcome was similar in
      the treatment groups for the first two years, we analyzed the adjustment and
      subjective well-being of families to the diabetes after a two-year follow-up
      period. A semi-structured interview by a psychologist who was blinded to the
      initial treatment length and medical history of the child showed that 74% of the
      families in the short-term and 58% in the long-term treatment groups had good
      overall psychosocial ability to function (ns); there were no unusual fears in 37%
      and 15% of the families (ns), respectively. After short-term treatment, families
      needed slightly but not significantly less time to be confident about the
      management of diabetes in the family. These findings show that the short-term
      initial hospital stay does not unfavorably affect the adjustment of the family to
      diabetes and should probably be preferred over the long-term initial hospital
      stay.

PMID- 7734898
TI  - Does a mutation of the glycine receptor modify GABA metabolism in startle
      disease?

PMID- 7734899
TI  - Prediction of the growth response of short prepubertal children treated with
      growth hormone. Swedish Paediatric Study Group for GH treatment.
AB  - The aim of this study was to identify predictors of the growth response to growth
      hormone (GH) during the first 2 years of GH treatment, using auxological data and
      the maximum GH response (GHmax) to provocation tests. The patients were 169
      prepubertal short children (27F, 142M), with Gmax values ranging from 0 to 65
      mU/l. Their mean age (+/- SD) was 8.3 +/- 2.4 years (range 3-13 years), mean
      height SDS -3.0 +/- 0.7 (range -1.5 to -6.0 SDS) and mean pretreatment height
      velocity was normal (+/- 0.0 SDS) (range -1.6 to +0.9 SDS). The increase in
      height SDS during the first 2 years of GH treatment (0.1 U/kg/day) varied from
      0.10 to 3.75 SDS, with younger children having a better growth response.
      Individual growth responses correlated (p < 0.001) with GHmax (r = -0.37), age (r
      = -0.35), 1-year pretreatment delta SDS (r = -0.25), mid-parental height SDS (r =
      0.34), height SDS at start of treatment (r = -0.22) and difference between height
      SDS of an individual child at the onset of GH treatment and mid-parental height
      expressed in SDS (diff SDS) (r = -0.43). In a multiple stepwise linear regression
      model, diff SDS and log GHmax were found to be the strongest predictors of the
      magnitude of the growth response. In the short children in this study who
      exhibited a broad range of GHmax values, 33% of the growth response during the
      first 2 years of treatment could be predicted.

PMID- 7734900
TI  - Thyroid gland volume as measured by ultrasonography in preterm infants.
AB  - The volume of the thyroid gland was determined by ultrasonography in 30 preterm
      infants (27-36 weeks' gestation) born in Madrid. Thyroid gland volume
      significantly increased (p < 0.01) with postnatal and postmenstrual age and was
      very well correlated with body weight, height and surface area (p < 0.01). Serum
      thyroid hormones 3,5,3'-triiodothyronine (T3) and free thyroxine (FT4) were
      linearly correlated with postnatal and postmenstrual age, thus T3 and FT4 levels
      were also correlated with thyroid gland volume (p < 0.05). We report measurements
      of the thyroid gland volume obtained by ultrasonography in this group of preterm
      infants. Quantitative determination of thyroid gland volume is more accurate for
      the diagnosis of goitre than clinical criteria. It is also interesting to
      determine the thyroid gland volume in the neonatal period when the thyroid is
      particularly hypersensitive to the effects of iodine deficiency and excess.

PMID- 7734901
TI  - Cerebral blood flow and left ventricular output in spontaneously breathing,
      newborn preterm infants treated with caffeine or aminophylline.
AB  - Aminophylline and caffeine are commonly used for prophylaxis of apnea in
      premature infants. Previous studies have indicated different effects of the drugs
      on cerebral circulation. Therefore, we have compared the acute effects of bolus
      administration of caffeine citrate or aminophylline on left ventricular output,
      heart rate, blood pressure and global cerebral blood flow. The study group
      consisted of 33 newborn, spontaneously breathing, preterm infants randomly
      assigned to receive either aminophylline 5 mg/kg (n = 19) or caffeine citrate 20
      mg/kg (n = 14). Two hours after iv drug administration, global cerebral blood
      flow measured by the Xe-clearance technique was significantly lower after
      aminophylline than after caffeine (mean (SD)): 13.2 (+2.9/-2.3) versus 17.2
      (+7.1/-5.1) ml/100 g/min) (p = 0.01). There were no other statistically
      significant differences in circulatory or ventilatory parameters between the
      groups. Further studies are needed to clarify the clinical relevance of these
      results.

PMID- 7734902
TI  - Thyroid autoantibodies, Turner's syndrome and growth hormone therapy.
AB  - The prevalence of thyroid autoantibodies, i.e. thyroglobulin antibodies and
      antibodies to thyroid peroxidase, was analyzed in 89 girls, aged 3-16 years (mean
      age 10 years), with Turner's syndrome. The analyses were performed before the
      start of growth-promoting treatment and during a follow-up period of 1-5 years.
      The patients were divided into four groups according to karyotype as follows:
      group 1, 45, X (n = 63); group 2 with structural abnormalities of the X
      chromosome (n = 10); group 3 with mosaicism but no structural abnormalities of
      the X chromosome (n = 10); and group 4, with isochromosome X of the long arm (n =
      12): 199 healthy girls aged 12 years, served as controls. Thyroid autoantibodies
      were demonstrated in 46 of 89 (52%) patients with Turner's syndrome compared with
      34 of 199 (17%) age-matched control girls (p < 0.001), thus confirming the
      relationship between thyroid abnormalities and Turner's syndrome. There was also
      an increase in the prevalence of thyroid antibodies with age. Simultaneous
      presence of both autoantibodies was significantly more frequent in group 1 (45,
      X) and group 4 (isochromosome X of the long arm) than in group 3 (mosaicism) (p =
      0.04 and p < 0.002, respectively) and significantly more frequent in group 4 than
      in group 1 (p < 0.05). During 12-60 months of growth-promoting treatment, no
      increase in the prevalence of thyroid antibodies was observed. The findings
      demonstrate the importance of continuous monitoring of thyroid function in girls
      with Turner's syndrome.

PMID- 7734903
TI  - Increased urinary excretion of collagen crosslinks in girls with Ullrich-Turner
      syndrome.
AB  - Skeletal abnormalities and "osteoporosis" are frequent features of Ullrich-Turner
      syndrome (UTS), but their cause remains largely unknown. In this study, we
      compared the urinary excretion of hydroxyproline (OHP), pyridinoline (PYD) and
      deoxypyridinoline (DPD) in 28 girls (bone age 3.5-11.0 years, mean 7.4 years)
      with UTS and 30 healthy prepubertal children (chronological age 3.9-10.9 years,
      mean 7.6 years). Expressed relative to the square of the height, the excretion of
      both collagen crosslinks was significantly higher in UTS than in controls (23.4%
      for PYD, 33.6% for DPD, p < 0.05). In contrast, no significant difference was
      found for OHP. The molar PYD/DPD ratio was significantly lower in UTS children
      than in controls (mean (+/- SD) 3.4 (+/- 0.41) versus 3.8 (+/- 0.55); p = 0.004).
      While the higher excretion of collagen crosslinks reflects enhanced bone
      resorptive activity in UTS, the lower PYD/DPD ratio might be due to structural
      alterations in collagen.

PMID- 7734904
TI  - Cyclosporin A in progressive system sclerosis.

PMID- 7734905
TI  - Determinants of blood glucose variability in adolescents with insulin-dependent
      diabetes mellitus.
AB  - Metabolic control and blood glucose variability in children with insulin
      dependent diabetes mellitus (IDDM) during and after puberty were studied. Seventy
      two children (43M, 29F), aged 10-19 years, with a 2-16-year duration of IDDM
      participated in the study. Fourteen of the patients were prepubertal (Tanner
      stage 1), 27 pubertal (Tanner 2-4) and 31 postpubertal (Tanner 5). They performed
      self-monitoring of blood glucose (SMBG) five times daily, every 2 days for 4
      weeks. The SD (SDbg) for all values in each patient was calculated as a measure
      of blood glucose variability. Weight-length index, linear growth velocity and
      Tanner stage were recorded. Hemoglobin (Hb)A1c, alkaline phosphatase and sex
      hormone levels in serum were analyzed. Subjectively experienced hypoglycemic
      episodes were recorded. HbA1c levels showed no relation to Tanner stage. SDbg was
      lower in stage 5 than in stages 2-4 (p = 0.02). There was no significant
      correlation between HbA1c and SDbg, but the variability was significantly lower
      in individuals with mean blood glucose in the lower quartile compared with those
      in the upper three quartiles (p < 0.001). Alkaline phosphatase concentration, as
      a measure of growth velocity, was the main independent determinant of SDbg (r =
      0.35, p < 0.005). There was an inverse correlation between levels of sex hormones
      and SDbg. We conclude that blood glucose variability is lower after than during
      puberty. This variability seems to be related to linear growth velocity or its
      biochemical marker.

PMID- 7734906
TI  - Scoring approaches to the recognition of cases of sudden infant death syndrome.
AB  - The aim of this study was to create a scoring method to distinguish between
      sudden infant death syndrome (SIDS) and cases of sudden death resulting from life
      threatening conditions (LTC). Four hundred infants less than one year old who
      died suddenly out of hospital in St Petersburg between 1983 and 1990 and who
      underwent a complete autopsy, were entered into the study. In 200 cases, the main
      diagnosis was SIDS, while in the remaining 200 cases, death was interpreted as
      resulting from LTC; 115 clinical and 240 morphological signs and symptoms were
      evaluated in each case. The statistical approach was based on the method of
      stepwise logistic regression analysis and it helped to identify 6 clinical and 12
      morphological signs which, combined, made it possible to distinguish between SIDS
      and non-SIDS (LTC) cases most accurately.

PMID- 7734907
TI  - Remission following an elemental diet or prednisolone in Crohn's disease.
AB  - The short- and long-term effects of an elemental diet in children with acute
      Crohn's disease were compared with those of prednisolone in historical controls.
      Clinical remission was induced in 25 of 30 and in 18 of 28 episodes treated for
      six weeks with an elemental diet and prednisolone. Patients with proximal disease
      had longer remission after treatment with an elemental diet (p < 0.05) than did
      patients with colonic disease after treatment with prednisolone (p < 0.01).
      Disease activity index score improved in both groups compared with the
      pretreatment scores (p < 0.05). However, the improvement in the elemental diet
      group was significantly better than in the prednisolone group (p < 0.001).
      Changes in linear growth were better after treatment with an elemental diet
      compared with steroids (p < 0.001). Serum albumin and haematocrit concentrations
      all improved significantly in the children treated with an elemental diet (p <
      0.001) but not in those treated with steroids. Thus an elemental diet was better
      than prednisolone in proximal disease and confirmed improved growth and
      nutritional status.

PMID- 7734908
TI  - Diagnostic imaging in children with urinary tract infection: the role of
      intravenous urography.
AB  - Ninety children referred to hospital with urinary tract infection (UTI) were
      investigated by iv urography (IVU), ultrasonography (US) and 99mTc
      dimercaptosuccinic acid scan (DMSA). Fifty-eight children also underwent
      micturating cystourethrography (MCUG). In 36 (40%) of the children, at least one
      result was abnormal. Abnormal findings were found in 29 children with IVU, in 10
      with US and in 16 with DMSA. Six of the 58 children had vesicoureteric reflux
      (VUR) in 8 kidneys. In 16 children, IVU was the only examination with an abnormal
      result, and in 10 of these the findings were considered important for treatment
      or prognosis. IVU is an important supplement to US and DMSA in investigation
      programs for children with UTI. IVU should be performed in cases of renal scars,
      dilatations or in children with recurrent infections.

PMID- 7734909
TI  - Prediction of acute otitis media with symptoms and signs.
AB  - We carried out a prospective study to analyse if it would be possible to predict
      the coexistence of acute otitis media on the basis of symptoms and signs of
      infection. Of the 658 patients admitted to hospital during the period concerned,
      197 (29.9%) had otitis media. For each child with otitis, the next patient of the
      same age was chosen as a control. The risk of having otitis media was increased
      among patients with cough, rhinitis and earache. All three variables together
      correctly classified 67% of those not having otitis media and 63% of those with
      acute otitis, compared with the 50% which would theoretically be achieved by
      chance alone. Prediction was worst (55%) among patients younger than 2 years of
      age not having otitis media and best among older patients who had otitis media,
      i.e. 78%. Prediction on these grounds would have caused significant over
      treatment, and one-third of the otitis cases among the youngest group would have
      been missed. Thus it is important to always examine the ears of a child with an
      infection in order to reliably exclude the possibility of acute otitis media.

PMID- 7734910
TI  - Reduced carnitine and antiepileptic drugs: cause relationship or co-existence?
AB  - Serum carnitine was measured longitudinally before and after therapy in 15
      patients receiving valproic acid, 14 patients receiving carbamazepine and 8
      patients receiving phenobarbital. The patients who received valproic acid showed
      a significant reduction in free (and total) serum carnitine (mean (SE) 37.6 (6.2)
      mumol/l without valproic acid, 29.1 (1.6) mumol/l with valproic acid (p <
      0.001)). Such an effect was not found in patients receiving carbamazepine or
      phenobarbital.

PMID- 7734911
TI  - Head trauma among children in Reykjavik.
AB  - The incidence of head trauma (ICD9 850-854) among children in the Reykjavik area,
      aged 0-14 years, was studied over a 5-year period, 1987-1991, using hospital
      records. On average, 72 children with head trauma were admitted to hospital each
      year, indicating an annual incidence of 1.70 per 1000 population. Fourteen
      percent of children admitted to hospital with head trauma suffered the more
      severe forms of brain injury (ICD9 851-854) (annual incidence of 0.28 per 1000).
      Seven children died from brain injury, indicating an annual death rate of 0.03
      per 1000. Falls were the most common cause of head trauma (62%), followed by
      traffic accidents (19%). On average, one to two severely brain-injured children
      received rehabilitation each year.

PMID- 7734912
TI  - Tubal catheterization for intrafallopian insemination and transvaginal gamete
      (GIFT) or zygote intrafallopian transfer (ZIFT): our experience in a total of
      1128 treatment cycles.
AB  - PURPOSE: Our purpose was to increase the number of fertile spermatozoa at the
      natural site of fertilization by retrograde tubal insemination (TV-IFI;
      transvaginal intrafallopian insemination) and also to perform transvaginal GIFT
      or ZIFT (TV-GIFT or TV-ZIFT) avoiding the laparoscopic procedure, especially in
      selected high-risk cases. RESULTS: The method was used in a total of 1128
      treatment cycles (948 for TV-IFI and 180 for TV-GIFT or TV-ZIFT). TV-IFI was
      possible in 882 of the 948 cycles, resulting in 108 clinical pregnancies
      (12.24%). The remaining 66, due to bilateral tubal catheterization failure
      (6.9%), underwent intrauterine insemination (IUI) instead. Bilateral TV-IFI gave
      better results than unilateral, while combination with IUI did not seem to
      improve the outcome. Of the 180 cycles prepared for TV-GIFT or ZIFT the procedure
      was completed in 166, resulting in 24 clinical pregnancies (19% per patient and
      14.45% per cycle). Due to bilateral tubal catheterization failure (8.2%) in the
      remaining 14 cycles (9 patients), IVF-ET was employed as an alternative.
      CONCLUSION: Simple and cost-effective TV-IFI may achieve a reasonable pregnancy
      rate, justifying its application in cases with previously failed IUI and before
      entering the IVF program. On the other hand, TV-GIFT or ZIFT, although less
      effective than the classical laparoscopic approach and IVF-ET, is worth pursuing,
      considering its safety and the minimal surgical intervention without anesthesia,
      and especially in selected high-surgical risk and obese patients.

PMID- 7734913
TI  - Intracytoplasmic single sperm injection: preclinical training and first clinical
      results.
AB  - OBJECTIVE: Our purpose was to reduce oocyte damage before clinical application of
      intracytoplasmic single sperm injection by training on aged unfertilized oocytes.
      DESIGN: Intracytoplasmic single sperm injection (ICSI) was accomplished by
      micromanipulation of sperm and oocytes. PATIENTS: Thirty-four patients consented
      to donate unfertilized aged oocytes to train for ICSI. Forty-four patients
      suffering from severe male infertility were treated with ICSI. INTERVENTION:
      Oocytes were inseminated by intracytoplasmic single sperm injection. MAIN OUTCOME
      MEASURES: Oocyte damage and fertilization and pregnancy rates were the outcome
      measures. RESULTS: One hundred fifty-one aged unfertilized oocytes were gathered
      for training of which 121 were injected with a single sperm and 30 without a
      spermatozoon as a control group for activation. Oocyte damage, initially as high
      as 40%, was reduced to 15% after 60 oocytes. Normal fertilization (2PN) occurred
      in 18%, and polyploidy in 4.4%. The cleavage rate was 69%; none of these embryos
      were transferred. In the control group, seven oocytes were damaged, seven (30%)
      showed one pronucleus, and one showed two pronuclei. No cleavage was observed in
      the control group. In the clinical trial, 44 patients (61 cycles) were clinically
      treated with the same ICSI procedure, including 575 of 721 collected oocytes.
      Damage was 13%, activation was 11%, normal fertilization was 30%, and 5 (1%)
      polypoid zygotes were observed. The fertilization rate ranged from 5 to 100%,
      with a mean of 39.5 +/- 4% (SE). Nine patients had no fertilization (15%). Ninety
      six percent of the zygotes cleaved and 47% were at the four-cell stage 45 hr
      after injection. One hundred twelve embryos were replaced in 48 transfers (2.3
      embryos/ET). One live birth, one miscarriage, and eight ongoing pregnancies were
      obtained (22%/ET). CONCLUSION: Preclinical practice on aged unfertilized oocytes
      seems useful before starting clinical ICSI, as the high initial oocyte damage can
      be reduced and subsequent clinical treatment successfully applied.

PMID- 7734914
TI  - Electron microscopic study of human sperm membrane isolation.
AB  - OBJECT: Our purpose was to isolated pure, homogeneous human sperm membranes, free
      of cellular contaminants. METHODS: Donor semen samples collected after
      masturbation were stored at -70 degrees C and eventually pooled. Each attempt at
      sperm membrane isolation required 800 x 10(6) spermatozoa which were sonicated by
      ultrasound (40% output; Vibra Cell). The effect of sonication time (3 x 5, 3 x
      15, and 180 sec) on membrane isolation was investigated. Sonicated samples were
      centrifuged (500 g, 5 min) and the supernatant was pipetted off. The supernatant
      of the centrifuged sample was layered on either a sucrose cushion (supernatant on
      1.6 M sucrose) or a discontinuous sucrose gradient and centrifuged (100,000 g, 1
      hr). Contents of supernatants of sonicated samples and fractions (sucrose
      interfaces) were then fixed in 1.0% tannic acid and 2.5% buffered glutaraldehyde
      and examined electron microscopically using standard procedures. RESULTS: (1) The
      optimal sonification time was found to be 3 x 15 sec. (2) Membrane isolation
      using a sucrose cushion was found to be inadequate, showing significant cellular
      contamination. (3) Sperm membrane isolation from the sucrose interface between
      0.75 and 1.05 M sucrose was found to be most effective. CONCLUSION: The advantage
      of this method is its simplicity. The drawback of this method is the large number
      of spermatozoa required for membrane purification.

PMID- 7734915
TI  - Minimum essential medium alpha (MEM) enhances assisted reproductive technology
      results. I. Mouse embryo study.
AB  - PURPOSE: Our purpose was to find a medium to enhance mouse zygote development
      and, hopefully, to apply the results to a coculture system and to enhance the ART
      pregnancy rate. DESIGN: The study was designed to compare different media's
      support of mouse zygote development with/without serum supplement. The outcome
      measure was the percentage of mouse zygotes/embryos that developed to the
      expanded blastocyst and hatchout stage. RESULTS: (1) Using human tubal fluid
      (HTF), one-cell zygotes had a 34.6 +/- 5.2% (mean +/- standard deviation)
      development rate, and two-cell embryos a 86.5 +/- 3.2% development rate. (2)
      Minimum essential medium alpha (MEM) showed the best results (52.2 +/- 14.5%)
      among Ham's F-10 (19.1 +/- 6.3%), HTF (26.8 +/- 8.2%), NCTC-135 (38.8 +/- 12.6%),
      MEM with nuclei acid (24.6 +/- 10.0%), and Dulbecco's modified Eagle medium (28.0
      +/- 20.2%). (3) With the serum supplement, there was no significant difference
      among Ham's F-10 (21.5 +/- 23.7), HTF (29.3 +/- 10.4%), NCTC-135 (36.5 +/- 6.2%),
      and MEM (38.8 +/- 17.9%). CONCLUSION: MEM is the best medium among the six media
      examined. Preliminary study showed that MEM gave a good clinical pregnancy rate
      (29%).

PMID- 7734916
TI  - Platelet activating factor treatment of spermatozoa enhances rabbit oocyte
      fertilization following subzonal sperm insertion.
AB  - PURPOSE: The objective of this study was to evaluate the effects of spermatozoal
      platelet activating factor (PAF) treatment on fertilization rates employing
      subzonal sperm insertion in the rabbit. STUDY DESIGN: Oocytes (n = 130) with
      distinct first polar bodies were injected with three to seven motile spermatozoa.
      Half (n = 65) of the oocytes were injected with PAF-treated sperm, whereas the
      other half (n = 65) served as controls and were injected with nontreated sperm.
      Fertilization rates were assessed by the formation of two pronuclei followed by
      cleavage to the two-cell stage. RESULTS: In the group of oocytes injected with
      PAF-treated sperm, we noted a significant (P < 0.001) improvement in
      fertilization rates, 61.5% (40/65), vs. control nontreated sperm, 20.0% (13/65).
      Subsequent cleavage to the two-cell stage was noted for 95% (38/40) in the
      treated vs 92.3% (12/13) in the nontreated fertilized zygotes. CONCLUSION: We
      conclude that PAF treatment of rabbit spermatozoa prior to subzonal insertion
      improves fertilization rates and may be of clinical significance in assisted
      reproductive programs.

PMID- 7734918
TI  - Ovarian pregnancies after oocyte donation in three menopausal patients treated by
      laparoscopy.

PMID- 7734917
TI  - Optimization of superovulation in the reproductively mature mouse.
AB  - Optimum gonadotropin doses and chronology were established for the induction of
      superovulation in sexually mature hybrid mice (BALB/cBy x C57BL/6By). A regime of
      12 IU pregnant mares' serum gonadotropin (PMSG), followed 48 hr later by 20 IU
      human chorionic gonadotropin (hCG) administered 1 hr before the midpoint of the
      light cycle (1200), gave the maximum ovulatory response. There was no evidence
      that endogenous luteinizing hormone influenced the superovulation response to
      exogenous gonadotropins. Fewer than 50% of zygotes reached the blastocyst stage
      (90-93 hr post hCG), with the greatest rate of loss at the two- to four-cell
      stage. Litter size following superovulation was 19.6 +/- 0.9. There was no
      significant difference between the number of blastocysts observed and litter
      size. Similarly, counts of mature follicles in ovaries prior to hCG stimulation
      were not significantly greater than the number of secondary oocytes that
      subsequently ovulated. These data indicate that standard superovulation protocols
      may require fine-tuning to maximize productivity and confirm that embryo loss is
      greatest between the first cleavage division and blastocyst formation.

PMID- 7734919
TI  - Effect of superovulation on early pregnancy factor activity in mice.

PMID- 7734920
TI  - The influence of uterine position on pregnancy rates with in vitro fertilization
      embryo transfer.
AB  - We found no difference in clinical pregnancy rates following IVF-ET in women with
      anteverted versus retroverted uteri. Patients can be reassured that the
      probability of clinical pregnancy following IVF-ET is not compromised by uterine
      position.

PMID- 7734921
TI  - Pregnancy and delivery after intracytoplasmic injection of an immobilized, killed
      spermatozoon into an oocyte.

PMID- 7734922
TI  - X-ray fluorescence in the assessment of inter-elemental interactions in rat liver
      following lead treatment.
AB  - Energy dispersive X-ray fluorescence technique was employed to study the
      interactions of lead (50 and 100 mg/kg body wt) with K, Fe, Cu, Zn, Br and Rb in
      rat liver. Lead was administered orally to rats daily for dosage periods of 1 and
      4 months (short and long terms). Hepatic Fe levels were found to increase
      significantly with the supplementation of low and high doses of lead for both the
      treatment periods, although the increase was more pronounced following long-term
      treatment. The levels of hepatic K, Cu and Br were seen to decrease significantly
      over both time intervals. Moreover, hepatic Rb contents were lowered with the
      short-term supplementation of low doses of lead. In contrast, Rb and Zn levels
      were increased when lead was administered for the longer period at both dose
      levels.

PMID- 7734923
TI  - Therapeutic potential of meso 2,3-dimercaptosuccinic acid or 2,3
      dimercaptopropane 1-sulfonate in chronic arsenic intoxication in rats.
AB  - The therapeutic efficacy of two thiol chelators, meso 2,3-dimercaptosuccinic acid
      (DMSA) or 2,3-dimercaptopropane sulfonate (DMPS) in treating chronic arsenic
      intoxication was investigated in male rats. Both the chelators were effective in
      promoting urinary arsenic excretion and restoring arsenic induced inhibition of
      blood delta-aminolevulinic acid dehydratase activity and hepatic glutathione
      level. Elevation of urinary delta-aminolevulinic acid excretion and arsenic
      concentration in blood, liver and kidneys were reduced significantly by both the
      chelators. Histopathological lesions induced by arsenic were also effectively
      reduced by the above chelators. DMSA being more effective than DMPS. The results
      suggest DMSA and DMPS to be effective antidotes for treating chronic arsenic
      toxicity in experimental animals.

PMID- 7734924
TI  - Embryotoxicity of silver ions is diminished by ceruloplasmin--further evidence
      for its role in the transport of copper.
AB  - The effect of alimentary administration of silver salts upon embryogenesis in
      rats was studied. Feeding of female rats throughout the term on a regular diet
      supplemented with AgCl did not cause alterations of their physiological
      functions, despite the fact that enzymatically active copper-containing
      ceruloplasmin (CP) was eliminated from the blood plasma. However, developmental
      abnormalities of embryos, their prenatal death or the 100% mortality of the
      newborns in the first 24 h of life was seen. Copper content in placenta and fetal
      tissues was strongly diminished. Cu, Zn-superoxide dismutase (SOD) activity
      decreased in cytoplasm of embryonic cells along with a drop, though less
      pronounced, in the tissues of the pregnant females. Embryotoxicity of AgCl was
      seriously diminished by repetitive injections of native CP to the pregnant rats.
      Such treatment resulted in an increase of SOD activity in placenta and embryonic
      tissues. The mortality of the newborns also became less. It is suggested that the
      embryotoxic effect of AgCl is caused by its ability to interfere with copper
      metabolism, in particular by altering the copper-transporting function of CP.

PMID- 7734926
TI  - Solvation of platinum anti-cancer drugs in methanol-water mixtures.
AB  - Solubilities and transfer chemical potentials of carboplatin, cisplatin,
      iproplatin, and several related platinum complexes have been determined in
      methanol-water mixtures. The range of solvation behaviour is discussed in
      relation to possible oral administration of complexes of this type.

PMID- 7734927
TI  - Gas chromatographic determination of enantiomers as diastereomers following pre
      column derivatization and applications to pharmacokinetic studies: a review.
AB  - The introduction of chiral chromatographic methods has revolutionized the art of
      separation and quantitation of chiral drugs in biological fluids. A large number
      of chiral derivatization reagents for various functional groups are available
      commercially. Therefore, pre-column derivatization methods have become attractive
      and simple for the gas chromatographic assays in biological fluids. The intent of
      this article is to review the pre-column chiral derivatization reagents employed
      in gas chromatographic separations and analyses of enantiomers. A discussion of
      numerous procedures necessary to develop a quantitative gas chromatographic assay
      method for drug enantiomers is presented. In this regard, quantitative gas
      chromatographic assays based on this approach have been applied to investigate
      the stereoselective pharmacokinetics of several chiral drugs such as
      fenfluramine, norfenfluramine, methylphenidate, etodolac, propranolol, suprofen
      and methoxyphenamine.

PMID- 7734925
TI  - Binding characterization of the iron transport receptor from the outer membrane
      of Escherichia coli (FepA): differentiation between FepA and FecA.
AB  - The dissociation constants for the binding of ferric enterobactin with FepA and
      FecA are quantitated with displacement experiments. It is found that Kd for FepA
      is 12 times lower than the one for FecA. This indicates that FepA is an high
      affinity receptor while FecA binds ferric enterobactin with a lower affinity.
      Monoclonal antibodies specific for binding epitopes of FepA inhibit the binding
      of ferric enterobactin with purified FepA. These same antibodies do not inhibit
      the binding of ferric enterobactin with purified FecA. This indicates that the
      binding epitopes in FecA and FepA are different.

PMID- 7734928
TI  - Enantiomeric separation and sensitive determination of D,L-amino acids
      derivatized with fluorogenic benzofurazan reagents on Pirkle type stationary
      phases.
AB  - The enantiomeric separations of D,L-amino acids derivatized with fluorogenic
      reagents, 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), 4-(N,N
      dimethylaminosulphonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) and 4
      aminosulphonyl-7-fluoro-2,1,3-benzoxadiazole (ABD-F) by high-performance liquid
      chromatography (HPLC) on various Pirkle type chiral stationary phases (CSPs,
      Sumichiral OA series) with citric acid in methanol as a mobile phase were
      studied. Since the least retention and no separation was observed for the
      derivatives of racemic phenylalanine methyl-ester, -amide and a drug without an
      alpha-carboxyl group, the carboxylic acid group of the amino acid derivatives
      seemed to contribute to the enantioselective fixation of the derivatives through
      hydrogen bonding on the N-acyl-amino acid amide moiety of the CSP. The
      enantioselective retention of the derivatives was attained through the (S) or (R)
      configuration of valine, phenylglycine, naphthylglycine, naphthylethylamine or
      the tert-leucine moiety in the CSP. The 2,1,3-benzoxadiazole (benzofurazan)
      moiety in the derivatives helps the effective fixation of the derivatives through
      a pi-pi interaction with an aromatic moiety such as a 3,5-dinitrophenyl or
      naphthyl group in the Pirkle type chiral stationary phases. D-Amino acids in
      biological samples were easily determined utilizing the present derivatization
      with NBD-F, enantiomeric separation and fluorometric detection (530 nm em/470 nm
      ex) following deproteinization of biological samples (serum or brain homogenate)
      with methanol and centrifugation. The applications of the method were clearly
      demonstrated by the following results; D-Ala was detected in sera of healthy
      volunteers at a level of 0.48-3.10 microM. D-Lys was found in the serum of a
      patient with myeloma and requiring renal dialysis, and D-Ser was found in rat and
      bovine cerebrum. Peak identification was performed by use of different types of
      stationary phases especially those bearing the opposite configuration to that of
      the chiral centre.

PMID- 7734929
TI  - Degradation of organophosphorus and carbamate pesticides in soils--HPLC
      determination.
AB  - Best conditions suited for the extraction and trace analysis of dimethoate,
      malathion, methyl-parathion, carbaryl, carbendazim and carbofuran in soils, using
      HPLC, were established. This was followed by studies related to persistence of
      residues in different soils. Half-life and time taken for 95% dissipation were
      determined in each case. Higher pH, moderate moisture and high calcium carbonate
      content aided degradation while organic matter increased persistence.

PMID- 7734930
TI  - Mannitol prevents methionine sulphoxidation mediated electrophoretic
      heterogeneity of apolipoprotein A-I.
AB  - Hybrid isoelectric focusing of apolipoprotein A-I in polyacrylamide gels with
      immobilized pH-gradients under non-denaturing conditions resulted in the
      occurrence of additional bands which could prevent the specific and sensitive
      detection of genetic variants. Hybrid isoelectric focusing of two
      chromatographically distinguishable apolipoprotein A-I isoforms that differ by
      sulphoxidation of methionine residues, apo A-I(Met) and apo A-I(MetSO), revealed
      that the additional bands were caused by this post-translational modification.
      Several antioxidative additives and conditions were compared for their ability to
      prevent methionine sulphoxidation in apolipoprotein A-I. In the presence of 200
      g/L mannitol in the gel, apolipoprotein A/I focused as a single band. Since
      methionine sulphoxidation in proteins is a general phenomenon either taking place
      in vivo or in vitro by isoelectric focusing, we conclude that isoelectric
      focusing in the presence of mannitol will improve the quality of resolution of
      many proteins in gels with immobilized pH-gradients.

PMID- 7734931
TI  - Determination of oxeladin in human plasma by gas chromatography--mass
      spectrometry.
AB  - A capillary gas chromatographic method with mass-selective detection was
      developed for the determination of oxeladin in human plasma. Plasma samples (1
      mL) were alkalinized and extracted using 5mL of hexane: isoamyl alcohol (99:1).
      The method was demonstrated to be sensitive (limit of quantitation at 1 ng/mL),
      linear between 1 and 150 mg/mL, accurate and precise enough (mean error and mean
      coefficient of variation at the limit of quantitation were 2.3 and 13.3%,
      respectively) to support pharmacokinetic evaluation of the drug at doses down to
      30 mg.

PMID- 7734932
TI  - Measurement of clozapine and norclozapine in plasma/serum by high performance
      liquid chromatography with ultraviolet detection.
AB  - A simple method for the measurement of clozapine and its N-desmethyl metabolite
      in human plasma or serum by high performance liquid chromatography is described.
      An internal standard (aqueous nortriptyline, 4 mg/L) (50 microL) and Tris buffer
      (2 mol/L, pH 10.6) (100 microL) are added to plasma/serum (200 microL) and the
      analytes and internal standard extracted into methyl tert-butyl ether (200
      microL). The extracts are analysed on a 150 mm column containing Spherisorb S5SCX
      using methanol containing ammonium perchlorate (35 mmol/L, pH 6.7) as eluent at a
      flow rate of 1.5 mL/min. Detection is by ultraviolet absorption (215 nm). The
      limit of detection is better than 0.05 mg/L for both analytes and the intra-assay
      precision (CV) for clozapine and norclozapine was 5.3 and 7.3% at 0.5 mg/L and
      2.6 and 2.8% at 1.5 mg/L, respectively. The method can be applied to the
      measurement of these compounds in plasma after acute overdosage, for the
      assessment of compliance in patients apparently refractory to therapy and to
      identify interactions between clozapine and other neuroleptic and antidepressant
      drugs which may effect toxicity.

PMID- 7734933
TI  - Purification of murine immunoglobulin M from spent tissue culture supernatant by
      one-step gel filtration chromatography procedure.
AB  - Optimal purification of immunoglobulin M (IgM) grown as spent tissue culture
      supernatant can be achieved by a straightforward size-exclusion chromatography
      procedure. Preparative isolation of IgM was achieved by precipitation with
      saturated ammonium sulphate to achieve a 45% solution. IgM was then purified by
      gel filtration chromatography with a solution of 100 mM Tris + 150 mM NaCl at pH
      8. Denaturing electrophoresis and Western immunoblotting revealed two prominent
      bands at 80 and 25 kDa, indicative of the heavy and light chains of IgM
      respectively. The specific immunoreactivity of this IgM was assessed by a
      modified enzyme antigen capture assay. In contrast to affinity and ion-exchange
      chromatographies, gel filtration allows retention of IgM immunoreactivity.

PMID- 7734934
TI  - A highly sensitive method to quantify triazolam and its metabolites with liquid
      chromatography--mass spectrometry.
AB  - We established a highly sensitive method to determine triazolam and its major
      metabolites, alpha-hydroxytriazolam and 4-hydroxytriazolam, in human plasma and
      urine with a liquid chromatography-mass spectrometry system which incorporates an
      atmospheric chemical ionization interface. A plasma sample and a urine sample
      after solvent extraction were injected into an ODS column of reversed phase with
      a mobile phase in a linear solvent gradient of initially 50 mM ammonium acetate
      (pH 4.0) 50%:methanol 50% and 15 min later methanol 100%; quantification limits
      of as low as 20 pg/mL at an SNR of 3 were obtained for each compound. With
      diazepam as an internal standard, recovery yields of 84, 81, and 77% were
      obtained for triazolam, alpha-hydroxytriazolam and 4-hydroxytriazolam,
      respectively.

PMID- 7734935
TI  - Sensitive determination of salmon calcitonin, by means of pre-column
      derivatization, HPLC and fluorometric determination.
AB  - A high sensitive analytical method for salmon calcitonin (sCT) was established by
      means of derivatization with a fluorescence labelling agent, DBD-F, followed by
      HPLC separation and fluorescence detection at 558 nm with excitation at 430 nm.
      Under optimized conditions (DBD-F, 0.1 M borate buffer (pH 8.5):acetonitrile
      (70:30, v/v)), three molecules of DBD-F reacted with one sCT molecule in the
      presence of 1 mM sodium dodecyl sulphate (SDS) at 50 degrees C for 3 h. The
      detection limit for the sCT derivative was 20 fmol. A linear relationship was
      obtained between the amount of sCT on column and the peak heights in the range of
      35-8000 fmol.

PMID- 7734936
TI  - High-performance liquid chromatography and fluorometric detection of
      arachidonylethanolamide (anandamide) and its analogues, derivatized with 4-(N
      chloroformylmethyl-N-methyl)amino-7-N,N-dimethylaminosulp honyl-2,1 ,3-
      benzoxadiazole (DBD-COCl).
AB  - The endogeneous ligand for the cannabinoid receptor, arachidonylethanolamide
      (anandamide) and its analogues, oleinylethanolamide, palmitylethanolamide and
      eicosapentaenoylethanolamide, were derivatized with a fluorogenic reagent, 4-(N
      chloroformylmethyl-N-methyl)amino-7-N,N-dimethylaminsulpho ny1-2,1,3-
      benzoxadiazole (DBD-COCl). They were separated on a reversed phase HPLC with a
      mobile phase of acetonitrile:water. The fluorometric detection of the derivatives
      was made at 560 nm with excitation at 450 nm and the detection limits for
      anandamide was 20 fmol on column. The structures of DBD-CO-ethanolamides were
      confirmed by liquid chromatography-atmospheric pressure chemical ionization-mass
      spectrometry (LC-APCI-MS).

PMID- 7734937
TI  - Interactions of psoralen-derivatized oligodeoxyribonucleoside methylphosphonates
      with vesicular stomatitis virus messenger RNA.
AB  - The ability of oligonucleotides to interact selectively with their targets is an
      important consideration in the design of antisense oligonucleotides. This is
      especially important in the case of antisense oligomers, such as psoralen
      derivatized oligomers, which can irreversibly bind to their targets. We have
      studied the interactions of a series of psoralen-derivatized antisense
      oligonucleoside methylphosphonates with the mRNAs of vesicular stomatitis virus
      (VSV), mRNAs that have a high degree of sequence homology. Cross-linking
      reactions were carried out under conditions of low ionic strength in order to
      reduce mRNA secondary structure. A 12-mer, whose sequence was complementary to
      VSV M-mRNA and partially complementary to sequences found in N, NS, and G mRNA
      cross-linked extensively to N-message. On the other hand, 16-mers whose sequences
      were uniquely complementary to binding sites on N- or M-mRNA specifically and
      efficiently cross-linked to their targeted mRNAs over the temperature range 0
      degree to 37 degrees C. A reverse transcriptase-catalyzed primer extension assay
      was used to show that one of the N-specific oligomers cross-linked at the
      expected site on N-mRNA and to estimate the extent of cross-linking. The results
      demonstrate that psoralen-derivatized oligonucleoside methylphosphonates can
      cross-link in a sequence-specific manner if the sequences of these oligomers are
      chosen carefully so as to avoid extensive partial complementarity with other mRNA
      sequences.

PMID- 7734938
TI  - Properties of exonuclease-resistant, psoralen-conjugated
      oligodeoxyribonucleotides in vitro and in cell culture.
AB  - We have prepared oligodeoxyribonucleotides that are modified at the 3'-terminal
      with N4-(4-aminobutyl)deoxycytidine and derivatized at the 5'-end with a 4'-([N
      (aminoethyl)amino]methyl)-4,5',8-trimethylpsoralen, (ae)AMT, and whose sequences
      are complementary to vesicular stomatitis virus (VSV), N-protein mRNA, (ae)AMT
      II, or VSV M-protein mRNA, (ae)AMT-III. (ae)AMT-II cross-links exclusively to VSV
      N-mRNA when a mixture of the oligomer and poly(A+) RNA from VSV-infected cells is
      irradiated in vitro with long wavelength UV light at either 20 degrees or 37
      degrees C. N4-(4-Aminobutyl)deoxycytidine at the 3'-end of (ae)AMT-II does not
      appear to affect the binding or cross-linking of the oligomer to its target RNA.
      Oligomer (ae)AMT-II is completely resistant to hydrolysis by the 3'-5'
      exonuclease activity found in fetal calf serum whereas a similar oligomer,
      (ae)AMT-I, which contains a 3'-terminal deoxycytidine, is hydrolyzed within 30
      min when incubated at 37 degrees C. Intact (ae)AMT-II was found in both the cell
      lysate and cell culture medium after 12 hr of incubation with mouse L-cells along
      with d-(ae)AMTpT, which appears to result from endonuclease degradation of the
      oligomer. In contrast no intact (ae)AMT-I was found in either the cell lysate or
      the culture medium after 1 hr incubation. Although 10 microM (ae)AMT-II had no
      effect on VSV-protein synthesis in either unirradiated or UV-irradiated VSV
      infected mouse L-cells, 10 microM (ae)AMT-III inhibited VSV protein synthesis 30%
      in irradiated cells. These results show that introduction of a N4-(4
      aminobutyl)deoxycytidine at the 3'-end of an oligodeoxyribonucleotide
      significantly increases the resistance of the oligomer to degradation by 3'-5'
      exonucleases but does not interfere with its ability to bind selectively to
      complementary RNA. Further derivatization with psoralen creates an oligomer that
      can be triggered to cross-link with RNA in a sequence-specific manner, is taken
      up intact by mammalian cells in culture, and exhibits biological activity. In
      combination, these two modifications endow the oligodeoxyribonucleotide with
      novel properties that could be exploited in the design of antisense or antigene
      reagents for use in controlling gene expression in mammalian cells.

PMID- 7734939
TI  - Alpha beta chimeric antisense oligonucleotides: synthesis and nuclease resistance
      in biological media.
AB  - A new type of chimeric oligonucleotides composed of alpha- and beta-sections is
      described. The sequence of eight beta-nucleotides flanked at 3'- or/and 5'-ends
      by nuclease-resistant alpha-oligonucleotides has been chosen as an effector
      domain to form a substrate for RNase H. The synthesized oligonucleotides are
      complementary to the translation initiation site of the pim protooncogene mRNA.
      We used the chemical ligation method to prepare the chimeric oligonucleotides.
      The thermal stability of heteroduplexes formed by the alpha beta oligonucleotides
      with a complementary strand is not significantly altered compared to that of
      their beta-analogs. These oligonucleotides promote efficient RNase H-mediated
      cleavage of pim mRNA. Among the alpha beta oligonucleotides studied, one with an
      alpha-fragment bound by its 3'-end to the 3'-end of the beta-octanucleotide
      proved to be the most resistant to nucleolytic digestion in human plasma, calf
      serum, and murine fibroblast lysate. This alpha beta oligonucleotide directs more
      specific RNA cleavage by RNase H than its beta beta counterpart.

PMID- 7734940
TI  - Oligo(A), oligo(TG), and Alu repeats of DNA in chromatin are available for
      sequence-specific chemical modification with oligodeoxynucleotide derivatives.
AB  - Reaction of 4-(N-2-chloroethyl-N-methylamino) benzylphosphamides of
      oligonucleotides, which are targeted to the poly(A), poly(TG), and Alu repeats of
      eukaryotic DNA in chromatin and isolated nuclei from HeLa cells, has been
      investigated. It was found that the reagents alkylate DNA and some proteins due
      to specific complex formation. The affinity character of the reaction was proved
      by the fact that free corresponding oligonucleotides taken in excess or
      preliminary treatment of chromatin with S1 nuclease both prevent the biopolymers
      from the modification. Deproteinated DNA from the same cells does not react with
      oligonucleotide derivatives. This suggests that the chromatin DNA must have some
      structural features allowing oligonucleotide binding. Reactivity may be
      attributed to the existence of strongly negative supercoiled DNA regions
      containing single-stranded sequences or regions where DNA can unwind in the
      presence of complementary oligonucleotides. Results obtained suggest that in
      eukaryotic chromatin there are open DNA sequences available for affinity
      modification with oligonucleotide derivatives not only due to formation of triple
      helixes.

PMID- 7734941
TI  - Developmental regulation of antisense-mediated gene silencing in Dictyostelium.
AB  - In Dictyostelium, the expression of antisense transcripts has been successfully
      used to reduce or eliminate gene expression. In most cases this occurs on the
      level of RNA stability resulting in a loss of both sense and antisense transcript
      accumulation. We here show that the antisense effect is regulated during the
      developmental cycle, i.e., in certain developmental stages and under certain
      developmental conditions, complementary RNAs appear not to interact with each
      other, resulting in a failure to abolish expression of the gene of interest. We
      find that this is not only the case with artificially introduced antisense
      constructs but also with the endogenous, antisense-regulated PSV-A gene. Our data
      demonstrate that antisense-mediated gene silencing is conferred by a biochemical
      machinery that is subject to regulation in vivo. The results provide a basis to
      better understand this machinery and to dissect the components. They may also
      explain the failure of some antisense experiments in Dictyostelium and possibly
      in other organisms.

PMID- 7734942
TI  - Inhibition of in vitro transcription by oligodeoxynucleotides.
AB  - Single-stranded short phosphodiester oligodeoxynucleotides have been used to
      inhibit in vitro T7 transcription system. These oligodeoxynucleotides were
      complementary to either the 3'-5' or 5'-3' strand of the transcription initiation
      site of a plasmid containing the gag region of HIV. Our results show that
      incubation of this plasmid DNA with the oligodeoxynucleotide complementary to the
      template DNA strand (3'-5', sense oligo) showed efficient inhibition of
      transcription. Incubation of this plasmid with the oligodeoxynucleotide
      complementary to the 5'-3' strand (antisense oligo) or a random
      oligodeoxynucleotide failed to do so. The inhibition of gag transcription was
      specific since the sense oligo failed to prevent transcription of a plasmid
      containing U2 RNA sequences. The inhibition of transcription was not limited to
      T7 RNA polymerase but was also observed with SP6 RNA polymerase.

PMID- 7734943
TI  - HIV-1 rev antisense phosphorothioate oligonucleotide binding to human mononuclear
      cells is cell type specific and inducible.
AB  - A fluorescein-conjugated, antisense phosphorothioate oligonucleotide with
      specificity for HIV-1 rev sequence (FAM-anti-rev) was investigated for its
      ability to bind to specific subsets of human peripheral blood mononuclear cells.
      Oligonucleotide binding by CD4+ and CD8+ T cells, B cells, and monocytes isolated
      from 15 normal and 15 HIV-infected individuals was evaluated on both
      nonstimulated mononuclear cells and after 24-hr activation with
      phytohemagglutinin (PHA). In both normals and HIV-infected individuals, we found
      a significantly higher percentage of monocytes and B cells binding
      oligonucleotide in comparison to T cells. Oligonucleotide binding by both T cells
      and B cells was enhanced by 24-hr PHA stimulation while monocyte uptake was
      unchanged. In comparison to normal controls, HIV-1-infected patients showed
      slightly higher percentages of both unstimulated and PHA activated CD4+, CD8+,
      and CD25+ T cells binding oligonucleotide. The propensity for a high percentage
      of monocytes, which may act as an HIV-1 reservoir, to bind the anti-rev
      oligonucleotide and the enhanced binding by T cells in the HIV-1-infected patient
      samples provides some optimism for potential in vivo therapy of HIV-1 infection
      using antisense oligonucleotides.

PMID- 7734944
TI  - Iontophoretic delivery of oligonucleotide derivatives into mouse tumor.
AB  - Oligodeoxyribonucleotides (22-mers) were delivered through the skin of C3H mice
      in the region of a mammary gland tumor by means of iontophoresis. It was shown
      that the oligonucleotides enter the tumor, cross it, and reach all mouse organs.
      Electrophoretic analysis of the oligonucleotide extracted from tumor showed that
      the compounds were delivered in the tissue in the intact state.

PMID- 7734945
TI  - Inhibition of T4 polynucleotide kinase activity by phosphorothioate and chimeric
      oligodeoxynucleotides.
AB  - Whole and partially modified phosphorothioate oligodeoxynucleotides (ODN) were
      found to directly inhibit T4 polynucleotide kinase (PNK) activity, while
      phosphodiester ODN showed no detectable inhibition. This inhibition was found to
      be length dependent, as demonstrated by a 28-mer phosphorothioate ODN with an
      IC50 of 12 nM, and an 8-mer phosphorothioate ODN with an IC50 of 27,000 nM.
      Inhibition depended on the number and type of modified internucleotide linkages:
      a 20-mer phosphorothioate ODN had an IC50 of 21 nM, while a chimeric ODN with
      seven phosphorothioate linkages and an identical sequence showed no inhibition.
      On the other hand, the same sequence as a chimeric phosphorodithioate ODN (with
      seven dithioate linkages) had an IC50 of 580 nM. Four different chimeric
      phosphorodithioate ODN showed markedly different potencies of inhibition,
      suggesting that inhibition of PNK activity can be sequence specific.

PMID- 7734946
TI  - Regulatory considerations for oligonucleotide drugs: updated recommendations for
      pharmacology and toxicology studies.
AB  - This article describes pharmacology and toxicity studies for oligonucleotide
      drugs that are recommended for inclusion in the initial Investigational New Drug
      Application (IND), a first request to use an investigational drug in clinical
      trials. Recent observations of non-sequence-dependent cardiovascular toxicity and
      deaths in monkeys following intravenous infusions of phosphorothioates have
      raised a potential safety concern for oligonucleotide drugs. This concern should
      be considered by drug sponsors in designing pre-IND nonclinical development
      programs and Phase I clinical protocols. Pre-IND conduct of pharmacodynamic
      cardiovascular screening is highly recommended for defining safe clinical dosing
      regimens for phosphorothioate (and, possibly, other charged-backbone) oligomers.
      Additionally, drug sponsors are encouraged to (1) conduct research into-the
      mechanisms responsible for this dose-limiting toxicity, (2) institute liberal
      publication policies for research conducted under industrial sponsorship, and (3)
      communicate with reviewing divisions at FDA for updated guidance in this field
      when planning pre-IND safety studies. Recommendations for nonclinical studies
      during development of oligonucleotides will be modified as new information
      regarding the biological properties of oligonucleotides becomes available.

PMID- 7734947
TI  - E1BF/Ku interacts physically and functionally with the core promoter binding
      factor CPBF and promotes the basal transcription of rat and human ribosomal RNA
      genes.
AB  - We have previously characterized an RNA polymerase (pol) I transcription factor,
      E1BF, from rat cells. This protein is immunologically related to Ku autoantigen
      and is required in pol-I directed transcription of rodent ribosomal RNA gene
      (rDNA). Glycerol density gradient fractionation and in situ UV cross-linking
      analysis of the purified factor showed directly that it consists of a heterodimer
      of 85 and 72 kDa polypeptides. E1BF also interacted with the human core promoter
      and augmented transcription of human rDNA as much as fivefold in HeLa nuclear
      extract, whereas transcription from adenovirus major late promoter, CMV or SV40
      early promoters by pol II and of U6 and 5S RNA genes by pol III were either
      unaffected or minimally inhibited by the antibodies. Purified rat E1BF partially
      restored the suppression of human rDNA transcription by anti-Ku antibodies.
      Immunoprecipitation of rat cell extract with the anti-Ku antibodies followed by
      SDS-PAGE of the precipitated proteins and Southwestern analysis showed that E1BF
      interacts with CPBF, a core promoter binding factor. When the majority of CPBF
      and E1BF was removed from the reaction mixture by preincubation with a core
      promoter oligo nucleotide fragment, rDNA transcription was severely impaired.
      Addition of exogenous CPBF or E1BF to such a reaction resulted in significant
      restoration of the transcription, whereas inclusion of both factors caused
      further enhancement of rDNA transcription. These data demonstrate that E1BF is a
      basal pol I transcription factor that interacts with a core promoter binding
      factor both physically and functionally, and that is not a general pol II or pol
      III transcription factor.

PMID- 7734948
TI  - Synthesis and maturation of viral transcripts in herpes simplex virus type 1
      infected HeLa cells: the role of interchromatin granules.
AB  - The response of the cellular RNA processing machinery to herpes simplex virus
      type 1 (HSV-1) infection was studied at the ultrastructural level in HeLa cells
      and compared to the distribution of RNA polymerase II molecules and viral RNA.
      Immunogold labeling of RNA polymerase II molecules revealed that viral genome
      transcription was restricted to filaments in an intranuclear, virus-induced
      region. This region also contained viral RNAs as revealed by in situ
      hybridization of two biotinylated viral DNA probes: a probe encompassing a
      limited portion of the viral genome (the F fragment) and a probe for the total
      genome. In addition, the latter probe revealed large amounts of viral RNA within
      the clusters of interchromatin granules, intranuclear structures of normal cells
      that became enlarged during HSV-1 infection. Components of spliceosomes were
      localized by in situ hybridization with biotinylated U1 and U2 DNA probes. The
      large viral region contained only traces of U1 and U2 RNAs, probably because of
      the low frequency of splices of viral transcripts. The clusters of interchromatin
      granules, however, accumulated U1 and U2 RNAs with the same frequency as in
      noninfected cells. Poly(A) RNA was detected by in situ hybridization of a
      biotinylated poly(dT) probe. Some was present over the filaments of the virus
      induced region but most was accumulated in the clusters of interchromatin
      granules. Our data suggest, therefore, that the clusters of interchromatin
      granules, in addition to their involvement in spliceosome component assembly,
      might also be a transient storage site for some families of viral mRNA, possibly
      a sorting site that regulates their migration.

PMID- 7734949
TI  - The genomic structure of the human UBE1L gene.
AB  - The human UBE1L gene, for which the product may well play a role in the ubiquitin
      system because of its high degree of identity to the ubiquitin activating enzyme,
      is located at 3p21, a chromosomal region consistently showing loss of
      heterozygosity in lung cancer. The finding that UBE1L is well expressed in normal
      lung tissue, but hardly or not in lung cancer-derived cell lines, prompted us to
      investigate its genomic structure to find an explanation for the lack of
      expression in lung cancer. The gene has 22 exons distributed over 8.4 kb. Both
      anchored PCR experiments and mapping of DNase I-hypersensitive sites point to the
      region immediately upstream of exon 1 as the promoter site. Three moderately to
      well-informative polymorphisms were found, of which one is easily directly
      detectable. Cancer-specific mutations were not detected. The lack of expression
      in lung cancer cell lines correlated with a highly decreased sensitivity towards
      DNAse I of the promoter region and with an almost complete methylation of the
      HhaI site in the first exon. 5'-Azacytidine-induced demethylation did not result
      in a marked increase of the UBE1L mRNA level in the tumor cell lines. This leaves
      the possibility that mutation or absence of yet unknown transcription factors
      causes a regulatory block of the UBE1L gene.

PMID- 7734950
TI  - Aspects of splice site selection in constitutive and alternative pre-mRNA
      splicing.
AB  - RNA splicing is an indispensable step for expression of many eukaryotic genes.
      Combinations of 5' and 3' splice sites should be correctly selected in both
      constitutive and alternative splicing. Recent studies have revealed mechanisms of
      alternative splicing in some systems, in which specific regulators play vital
      roles in splice site selection. On the other hand, essential splicing factors
      such as SR proteins modulate splice site usage of general machinery. Specific
      regulators and splicing factors such as SR proteins have some common structural
      features. With these related components, a similar machinery of splice site
      selection is involved in constitutive and alternative splicing.

PMID- 7734952
TI  - Impairment of the melanogenic pathway in B16 melanoma cells transfected with
      class I H-2 genes.
AB  - Transfection of class I H-2Kb or H-2Kd into cells of a pigmented subclone of B16
      F10 BL6 (termed BL6-8) results in the loss of melanin production. In contrast,
      transfected BL6-8 cells expressing H-2Dd, H-2Ld, class I H-21Ak and/or the neor
      genes maintained their pigmented phenotype. Melanogenesis was also inhibited in
      cells which expressed the endogenous H-2Kb, but not the endogenous H-2Db, gene.
      In order to identify the specific defects in the melanogenic pathway responsible
      for the absence of melanin production, factors known to be related to the
      regulation of pigment formation were evaluated in H-2K-expressing cells. These
      studies showed that: (1) transfection of BL6-8 cells with the H-2Kb or H-2Kd, but
      not with the H-2Dd, H-2Ld or H-21Ak, genes was associated with complete
      inhibition of tyrosinase activity; (2) alpha-melanocyte-stimulating hormone (MSH)
      and theophylline (an inhibitor of cAMP phosphodiesterase) failed to stimulate
      tyrosinase activity in H-2K-positive cells, whereas tyrosinase activities in
      untransfected, or H-2DdH-2Ld, neor or H-21Ak-transfected cells were dramatically
      increased by those agents; (3) treatment with MSH had no effect on cAMP levels in
      H-2K-positive cells but stimulated cAMP levels more than 100-fold in H-2K
      negative cells; (4) in contrast to MSH, forskolin, a stimulator of adenylate
      cyclase, was able to stimulate cAMP levels in all cell lines tested, but in H-2Kb
      positive cells the levels of forskolin-induced cAMP were significantly less than
      those elicited in H-2Kb-negative cells; (5) electron microscopy showed that H-2K
      positive cells lacked mature melanosomes; (6) Northern blot analyses showed that
      H-2K-positive cells lacked mRNA for tyrosinase or for the MSH receptor. Taken
      together, expression of the endogenous or transfected H-2K gene in BL6 melanoma
      cells results in down-regulation of the entire melanogenic pathway, including the
      inhibition of tyrosinase and MSH receptor gene expression, cAMP responses and
      melanosomal biogenesis.

PMID- 7734953
TI  - Detection of a human DNA sequence correlated with melanocyte-like differentiation
      and tumour suppression after transfection into murine melanoma cells.
AB  - Since there is much indirect evidence for dominant suppressor genes for melanoma,
      we sought to isolate such a gene. Metastatic B16-F10 murine melanoma cells were
      lipofected with a normal human genomic library in a cosmid vector that also
      confers resistance to the drug G418. A few of the G418-resistant colonies
      acquired combinations of properties resembling those of normal melanocytes,
      including differentiated features (pigmentation, dendricity), slower growth, flat
      shape, monolayered colony form, stimulation of proliferation by a phorbol ester,
      and anchorage dependence. Four out of eight also showed reduced tumorigenicity in
      mice. Southern blotting indicated the presence of numerous cosmids in the
      melanocyte-like transfectants. DNA from one such line was used for secondary
      transfection. One secondary G418-resistant line showed pronounced melanocytic
      properties and marked tumour suppression in syngeneic and nude mice. A human
      repetitive sequence detected in this line was used in the polymerase chain
      reaction (PCR) to isolate intervening unique DNA sequences. One unique human
      sequence was attenuated in all tumors arising from both primary and secondary
      transfectants, suggesting close linkage with the sequence responsible for tumour
      suppression.

PMID- 7734951
TI  - Regulation of cyclin D1, DNA topoisomerase I, and proliferating cell nuclear
      antigen promoters during the cell cycle.
AB  - Cyclin D1, DNA topoisomerase I, and proliferating cell nuclear antigen (PCNA) are
      three important cell cycle regulatory proteins. Recently, their promoters have
      been isolated, thus facilitating molecular analysis of transcriptional control
      mechanisms of these genes. Transcription of these three promoters in stable K562
      transfectants during different cell cycle phases was analyzed after cell cycle
      synchronization. About 1 kb of 5' flanking region from either cyclin D1 or DNA
      topoisomerase I gene is sufficient to confer G1- or S-phase-specific
      transcription activity to chloramphenicol acetyltransferase (CAT) reporter genes,
      respectively. In contrast, 2.8 kb of 5' flanking sequences from the PCNA gene led
      to constitutive transcription, but the inclusion of a segment of the PCNA gene
      first intron, which contains evolutionarily conserved sequences, could enhance
      transcription in G1/S-enriched nuclei. This PCNA intron region contains a binding
      site recognized by the transcription factor E2F. To test whether this site is
      functional, we cotransfected PCNA-CAT genes with E2F-1 and DP-1 expression
      plasmids. Expression of the E2F-1/DP-1 heterodimer activated the CAT gene with
      the PCNA intron. Therefore, this intron region, involved in transcriptional
      activation at the cell cycle G1/S boundary, is also E2F inducible.

PMID- 7734954
TI  - The European Organization for Research and Treatment of Cancer (EORTC) Malignant
      Melanoma Cooperative Group 25th anniversary.

PMID- 7734955
TI  - Cytokine expression in human primary and metastatic melanoma cells: analysis in
      fresh bioptic specimens.
AB  - In recent years, several studies have documented that melanoma cell lines produce
      various cytokine/growth factors and their receptors. Since cell lines can acquire
      altered properties, such as changes in growth requirements, we studied
      constitutive cytokine gene expression in melanoma cells from 20 fresh surgical
      specimens: seven primary melanomas and 13 metastases (12 lymph-node metastases
      and one subcutaneous metastasis). After tumour cell isolation by discontinuous
      gradient, we tested for mRNA expression by means of reverse-transcriptase
      polymerase chain reaction. Most melanoma cells tested expressed growth factors:
      basic fibroblast growth factor (bFGF), interleukin (IL)1 alpha, IL-1 beta, IL-6
      and IL-8 and, in five cases out of 20, expressed granulocyte-macrophage colony
      stimulating factor (GM-CSF) (two out of five were also positive for GM-CSF
      receptor). Our results do not point to a direct correlation between cytokine
      expression and clinical stage at the time when the bioptic specimen was obtained.
      However, they allow us to suggest a possible metastatic tumour cell phenotype, in
      which autogenous GM-CSF expression could modulate immune response against the
      tumour cell itself or could potentiate metastatic colonization properties.

PMID- 7734956
TI  - Tetramodality treatment of human melanoma in vitro.
AB  - We evaluated the in vitro cytotoxic effects of combined human tumour necrosis
      factor alpha (TNF), human interferon gamma (IFN-gamma), melphalan (L-PAM) and
      hyperthermia (HTX) on human melanoma cell lines using the crystal violet assay.
      HTX (40 degrees C, 1 h) alone had no effect. The responses of the cell lines to
      TNF were in the rank order of 939 cells > 987 > 284 > C8161 > 852 > A2058
      approximately 0, and all displayed shallow dose-response curves; no significant
      thermal enhancement of TNF cytotoxicity was apparent with this heat dose. All
      cell lines were sensitive to L-PAM, with 284 cells being the most sensitive; HTX
      caused only slightly increased sensitization to L-PAM. The combination of TNF and
      L-PAM resulted in generally subadditive or additive cytotoxicity, with or without
      HTX. The response to IFN-gamma alone was heterogeneous; the 939, 284 and 852 cell
      lines were sensitive to a dose as low as 20 ng/ml, whereas the 987 line was
      resistant to 2.0 micrograms/ml, even with HTX. IFN-gamma enhanced the response to
      TNF only of the TNF-resistant A2058 cell line, but there was no enhancement of
      the response to L-PAM for any line. Thus, this tetramodality combination achieved
      generally subadditive or additive cytoxicity in vitro.

PMID- 7734957
TI  - Is the use of sunscreens a risk factor for malignant melanoma?
AB  - The relation between use of sunscreens, different host factors and malignant
      melanoma was investigated in a population-based, matched case-control study of
      malignant melanoma in the South Swedish Health Care Region, which has the highest
      risk for melanoma in Sweden, between 1 July 1988 and 30 June 1990. In total, 400
      melanoma patients and 640 healthy controls aged 15-75 years answered a
      comprehensive questionnaire regarding different epidemiologic variables,
      including questions on use of sunscreens and different constitutional factors.
      The use of sunscreens was not found to protect against developing malignant
      melanoma. Instead, an unexpected relation between the use of sunscreens and the
      risk of developing malignant melanoma was seen (odds ratio (OR) 1.8 for almost
      always vs never using sunscreens). A tentative dose-response relation was found.
      Virtually the same ORs were seen in both sexes. Furthermore, persons younger than
      50 years had a higher OR than persons older than 50 years. When different
      melanoma presentation sites were considered, lesions of the trunk were associated
      with sunscreen use in females (adjusted OR = 3.7 for almost always vs never using
      sunscreens), while lesions of the extremity or head and neck were associated with
      sunscreen use in males (adjusted OR = 3.2 for almost always vs never using
      sunscreens). Raised naevi on the left arm and freckling were shown to be the
      major constitutional risk factors (OR = 3.9 for more than three naevi vs none and
      OR = 1.4, respectively). The results were essentially unaltered in a
      histopathologically re-examined material. Further investigations are needed in
      order to form a basis for melanoma prevention.

PMID- 7734958
TI  - Elevated serum levels of interleukin-10 in patients with metastatic malignant
      melanoma.
AB  - Interleukin-10 (IL-10), originally described as a product of TH2 cell clones, has
      been recognized as a potential immunosuppressive cytokine. To investigate the
      relevance of IL-10 in melanoma patients in vivo, we studied IL-10 serum levels in
      104 untreated patients in different stages of the disease; 20 healthy subjects
      and 22 patients with inflammatory dermatoses served as controls. Serum levels
      were measured by ELISA. Only one of 31 patients with stage I melanoma (3%) and
      one of 16 stage II patients (6%) showed detectable IL-10 levels. Interestingly,
      six of 17 patients with lymph node metastases (stage III, 35%) and 29 of 40
      patients with widespread disease (stage IV, 73%) revealed IL-10 levels of 15-480
      pg/ml. No healthy person and only one control patient had a detectable IL-10
      serum level. The data suggest that IL-10 in melanoma patients may contribute to
      down-modulation of anti-tumour responses in vivo.

PMID- 7734959
TI  - Twenty-five years of pluridisciplinary approach for melanoma patients. The
      European Organization on Research and Treatment of Cancer Melanoma Cooperative
      Group (EORTC-MCG).
AB  - The EORTC Melanoma Group was created in 1969 by people of different disciplines
      who were, and still are, motivated by the need for a pluridisciplinary approach
      to melanoma. Table 1 lists the chairmen and secretaries who have served on the
      organization. The core organization is devoted to treatment of melanoma. In
      addition, there are subgroups for specific programs, listed below.

PMID- 7734960
TI  - Use of a gene expression system based on potato virus X to rapidly identify and
      characterize a tomato Pto homolog that controls fenthion sensitivity.
AB  - A novel transient gene expression system was used to study both the tomato
      disease resistance gene Pto and a Pto homolog designated Fen. The gene expression
      system was based on potato virus X (PVX). Tomato plants that were both
      susceptible to strains of Pseudomonas syringae pv tomato carrying the
      corresponding avirulence gene avrPto and insensitive to the insecticide fenthion
      were infected with in vitro-generated transcripts of PVX derivatives containing
      either Pto or Fen. Expression of the Pto gene from the virus genome failed to
      elicit P.s. tomato resistance, indicating that the PVX system is not suitable for
      the study of Pto. However, expression of the Fen gene resulted in sensitivity to
      fenthion. The utility of the PVX gene expression system was further demonstrated
      through structure/function studies of the Fen gene. A correlation was shown
      between Fen protein kinase activity and the ability of this protein to confer
      fenthion sensitivity to tomato. Furthermore, it was demonstrated that mutation of
      a putative N-terminal myristoylation site, proposed to be involved in membrane
      targeting, rendered the Fen protein inactive. Analysis of a Pto-Fen chimeric gene
      allowed the fenthion sensitivity domain to be localized to the C-terminal part of
      the Fen protein. Interestingly, expression of the Fen kinase from the PVX genome
      in Nicotiana spp resulted in a fenthion-independent necrotic response. Our
      results support the involvement of the Fen gene in a signal transduction
      pathway(s).

PMID- 7734961
TI  - Impaired photoassimilate partitioning caused by phloem-specific removal of
      pyrophosphate can be complemented by a phloem-specific cytosolic yeast-derived
      invertase in transgenic plants.
AB  - Constitutive expression of the Escherichia coli ppa gene encoding inorganic
      pyrophosphatase resulted in sugar accumulation in source leaves and stunted
      growth of transgenic tobacco plants. The reason for this phenotype was
      hypothesized to be reduced sucrose utilization and loading into the phloem. To
      study the role of PPi in phloem cells, a chimeric gene was constructed using the
      phloem-specific rolC promoter of Agrobacterium rhizogenes to drive the expression
      of the ppa gene. Removal of cytosolic PPi in those cells resulted in
      photoassimilate accumulation in source leaves, chlorophyll loss, and reduced
      plant growth. From these data, it was postulated that sucrose hydrolysis via
      sucrose synthase is essential for assimilate partitioning. To bypass the PPi
      dependent sucrose synthase step, transgenic plants were produced that express
      various levels of the yeast suc2 gene, which encodes cytosolic invertase, in
      their phloem cells. To combine the phloem-specific expression of the ppa gene and
      the suc2 gene, crosses between invertase- and pyrophosphatase-containing
      transgenic plants were performed. Analysis of their offspring revealed that
      invertase can complement the phenotypic effects caused by the removal of PPi in
      phloem cells.

PMID- 7734962
TI  - Specific expression in reproductive tissues and fate of a mitochondrial sterility
      associated protein in cytoplasmic male-sterile bean.
AB  - In common bean, cytoplasmic male sterility has been associated with a unique
      sequence found in the mitochondrial genome, designated pvs (for Phaseolus
      vulgaris sterility sequence). Within the pvs sequence, two open reading frames
      are encoded, ORF98 and ORF239. We have raised rabbit polyclonal antibodies
      against Pvs-ORF239 to evaluate the role of this putative male sterility
      associated protein. Histological investigation of pollen development revealed
      that in the male-sterile bean line, callose deposition was abnormal and
      microspores remained as tetrads as previously reported. Pvs-ORF239 was found to
      be localized within the reproductive tissues of the male-sterile bean line, in
      contrast to all other cytoplasmic male sterility systems studied to date. This
      protein was associated with mitochondria, the callose layer, and developing
      primary cell walls during microsporogenesis. Expression of pvs-orf239 was not
      detected in fertile plants containing restorer gene Fr2. These observations,
      together with previous reports, suggest that nuclear restorer gene Fr2 interferes
      with expression of the pvs region post-transcriptionally.

PMID- 7734963
TI  - Site-selected transposon mutagenesis at the hcf106 locus in maize.
AB  - The High chlorophyll fluorescence106 (Hcf106) gene in maize is required for
      chloroplast membrane biogenesis, and the hcf106-mum1 allele is caused by the
      insertion of a Robertson's Mutator Mu1 element into the promoter of the gene.
      Seedlings homozygous for hcf106-mum1 are pale green and die 3 weeks after
      germination, but only in the presence of Mutator activity conferred by active,
      autonomous Mu regulatory transposons elsewhere in the genome. When Mutator
      activity is lost, the mutant phenotype is suppressed, and homozygous plants have
      an almost wild-type phenotype. To isolate derivative alleles at the hcf106 locus
      that no longer require Mutator activity for phenotypic expression, we have
      developed a method for site-selected transposon mutagenesis in maize. This
      procedure, first described for Caenorhabditis elegans and Drosophila, involves
      using polymerase chain reaction (PCR) to screen pools of individuals for
      insertions and deletions in genes of known sequence. Pools of seedlings
      segregating for the progenitor allele hcf106-mum1 were screened by PCR for
      insertions and deletions associated with Robertson's Mutator. In a 360-bp target
      region, two new insertions and one deletion were identified in only 700 Mu-active
      gametes screened. One of the insertions was in the progenitor hcf106-mum1 allele
      and the other was in the wild-type allele, but all three new alleles were found
      to have break-points at the same nucleotide in the first intron. Unlike the hcf
      106-mum1 progenitor allele, the deletion and one of the insertions conferred pale
      green seedling lethal phenotypes in the absence of mutator activity. However, the
      second insertion had a weak, viable phenotype under these conditions.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7734964
TI  - Functional dissection of an abscisic acid (ABA)-inducible gene reveals two
      independent ABA-responsive complexes each containing a G-box and a novel cis
      acting element.
AB  - To elucidate the mechanism by which abscisic acid (ABA) regulates gene
      expression, the promoter of the barley ABA-responsive HVA22 gene has been
      analyzed by both loss- and gain-of-function studies. Previous reports indicate
      that G-box sequences, which are present in genes responding to a variety of
      environmental and physiological cues, are involved in ABA response. However, our
      data suggest that G-box sequences are necessary but not sufficient for ABA
      response. Instead, an ABA response complex consisting of a G-box, namely, ABRE3
      (GCCACGTACA), and a novel coupling element, CE1 (TGCCACCGG), is sufficient for
      high-level ABA induction, and replacement of either of these sequences abolishes
      ABA responsiveness. We suggest that the interaction between G-box sequences, such
      as ABRE3 in the HVA22 gene, and CE-type sequences determines the specificity in
      ABA-regulated gene expression. Our results also demonstrate that the ABA response
      complex is the minimal promoter unit governing high-level ABA induction; four
      copies of this 49-bp-long complex linked to a minimal promoter can confer more
      than 100-fold ABA-induced gene expression. In addition to ABA response complex 1,
      composed of ABRE3 and CE1, the HVA22 promoter contains another ABA response
      complex. The ABA responsiveness of this ABA response complex 2 relies on the
      interaction of G-box (ABRE2; CGCACGTGTC) with another yet unidentified coupling
      element. These two complexes contribute incrementally to the expression level of
      HVA22 in response to ABA.

PMID- 7734965
TI  - Directed tagging of the Arabidopsis FATTY ACID ELONGATION1 (FAE1) gene with the
      maize transposon activator.
AB  - The FATTY ACID ELONGATION1 (FAE1) gene of Arabidopsis is required for the
      synthesis of very long chain fatty acids in the seed. The product of the FAE1
      gene is presumed to be a condensing enzyme that extends the chain length of fatty
      acids from C18 to C20 and C22. We report here the cloning of FAE1 by directed
      transposon tagging with the maize element Activator (Ac). An unstable fae1 mutant
      was isolated in a line carrying Ac linked to the FAE1 locus on chromosome 4.
      Cosegregation and reversion analyses established that the new mutant was tagged
      by Ac. A DNA fragment flanking Ac was cloned by inverse polymerase chain reaction
      and used to isolate FAE1 genomic clones and a cDNA clone from a library made from
      immature siliques. The predicted amino acid sequence of the FAE1 protein shares
      homology with those of other condensing enzymes (chalcone synthase, stilbene
      synthases, and beta-ketoacyl-acyl carrier protein synthase III), supporting the
      notion that FAE1 is the structural gene for a synthase or condensing enzyme. FAE1
      is expressed in developing seed, but not in leaves, as expected from the effect
      of the fae1 mutation on the fatty acid compositions of those tissues.

PMID- 7734966
TI  - Low-temperature signal transduction: induction of cold acclimation-specific genes
      of alfalfa by calcium at 25 degrees C.
AB  - To study the role of calcium in cold acclimation, we examined the relationship
      between calcium influx and accumulation of transcripts of two cas (cold
      acclimation-specific) genes of alfalfa, cas15 and cas18. Whereas a decline in
      temperature from 25 to 15 degrees C had little effect on the influx of
      extracellular 45Ca2+, an increasing influx was observed when the temperature was
      lowered further. The influx of 45Ca2+ at 4 degrees C was nearly 15 times greater
      than at 25 degrees C. The addition of calcium chelators or of calcium channel
      blockers, which have been shown to prevent cold acclimation, inhibited the influx
      of extracellular 45Ca2+ as well as the expression of cas genes at 4 degrees C.
      The addition of a calcium ionophore or a calcium channel agonist to nonacclimated
      cells caused the influx of extracellular 45Ca2+ and induced the expression of cas
      genes at 25 degrees C. These results suggest that a cold-induced calcium influx
      plays an essential role in cold acclimation. To further study the role of
      calcium, we isolated two sequences corresponding to calcium-dependent protein
      kinases. The transcript level of one of them was markedly upregulated at 4
      degrees C. We propose a sequence of signaling events that is likely to occur
      early during cold acclimation and leads to the expression of cas genes and the
      development of freezing tolerance.

PMID- 7734967
TI  - Post-transcriptional cosuppression of beta-1,3-glucanase genes does not affect
      accumulation of transgene nuclear mRNA.
AB  - Silencing of a Nicotiana plumbaginifolia beta-1,3-glucanase (gn1) transgene in
      tobacco line T17 occurs in homozygous and in haploid plants with one transgene
      locus dosage per chromosome set. We have previously shown that the silent state
      is manifested by a reduced gn1 steady state mRNA level and results from a post
      transcriptional process that is under developmental control in homozygous T17
      plants. In this study, we show that specific endogenous beta-1,3-glucanase genes
      are cosuppressed with gn1 in homozygous T17 plants. We also demonstrate that the
      developmental timing of cosuppression depends on environmental conditions and
      that once silencing is established it is stably maintained during plant
      development. Analyses of additional transgenic tobacco lines revealed that gn1
      silencing is not restricted to the T17 line and showed that silencing can also
      take place in R0 plants containing independent loci in hemizygous states.
      Furthermore, silencing can also be obtained in progeny plants in which expressing
      loci have been combined. Importantly, cosuppression occurs via a post
      transcriptional mechanism that does not interfere with the accumulation of
      transgene nuclear mRNA. These results strongly suggest that the silencing
      mechanism operates at RNA transport and/or RNA stability levels.

PMID- 7734968
TI  - Palmitoyl-acyl carrier protein (ACP) thioesterase and the evolutionary origin of
      plant acyl-ACP thioesterases.
AB  - Acyl-acyl carrier protein (ACP) thioesterases play an essential role in chain
      termination during de novo fatty acid synthesis and in the channeling of carbon
      flux between the two lipid biosynthesis pathways in plants. We have discovered
      that there are two distinct but related thioesterase gene classes in higher
      plants, termed FatA and FatB, whose evolutionary divergence appears to be
      ancient. FatA encodes the already described 18:1-ACP thioesterase. In contrast,
      FatB representatives encode thioesterases preferring acyl-ACPs having saturated
      acyl groups. We unexpectedly obtained a 16:0-ACP thioesterase cDNA from Cuphea
      hookeriana seed, which accumulate predominantly 8:0 and 10:0. The 16:0
      thioesterase transcripts were found in non-seed tissues, and expression in
      transgenic Brassica napus led to the production of a 16:0-rich oil. We present
      evidence that this type of FatB gene is ancient and ubiquitous in plants and that
      specialized plant medium-chain thioesterases have evolved independently from such
      enzymes several times during angiosperm evolution. Also, the ubiquitous 18:1-ACP
      thioesterase appears to be a derivative of a 16:0 thioesterase.

PMID- 7734970
TI  - 1st Symposium on Experimental Rhinology and Immunology of the Nose. Dusseldorf,
      Germany, September 1993.

PMID- 7734969
TI  - Pollen specificity elements reside in 30 bp of the proximal promoters of two
      pollen-expressed genes.
AB  - Functional analyses previously identified minimal promoter regions required for
      maintaining high-level expression of the late anther tomato LAT52 and LAT59 genes
      in tomato pollen. Here, we now define elements that direct pollen specificity. We
      used a transient assay system consisting of two cell types that differentially
      express the LAT genes and both "loss-of-function" and "gain-of-function"
      approaches. Linker substitution mutants analyzed in the transient assay and in
      transgenic plants identified 30-bp proximal promoter regions of LAT52 and LAT59
      that are essential for their expression in pollen and that confer pollen
      specificity when fused to the heterologous cauliflower mosaic virus 35S core
      promoter. In vivo competition experiments demonstrated that a common trans-acting
      factor interacts with the pollen specificity region of both LAT gene promoters
      and suggested that a common mechanism regulates their coordinate expression.
      Adjacent upstream elements, the 52/56 box in LAT52 and the 56/59 box in LAT59,
      are involved in modulating the level of expression in pollen. The 52/56 box may
      be a target for the binding of a member of the GT-1 transcription factor family.

PMID- 7734971
TI  - Rhinitis as a mechanism of respiratory defense.
AB  - The incidence of rhinitis is on the increase, especially in towns and cities with
      high levels of pollution from motor traffic and industry. There is a growing body
      of evidence which links this increased incidence of rhinitis to chronic nasal
      irritation from industrial pollution. Studies on the mechanisms of nasal
      inflammation and the nasal immune response are now providing insights into the
      etiology of rhinitis. This knowledge will help in the development of therapies
      aimed at alleviating the symptoms of rhinitis and controlling the development of
      rhinitis in susceptible individuals. This review discusses some of the factors
      that may explain the increased incidence of rhinitis and examines basic
      mechanisms involved in the nasal response to infection and allergy.

PMID- 7734972
TI  - Mechanisms of nasal hyper-reactivity.
AB  - Hyper-reactivity to non-specific challenges has been considered a hallmark of
      asthma and is defined as an abnormal responsiveness of the bronchial airways to a
      variety of provocative agents. The mechanisms underlying hyper-reactivity in the
      upper and lower airways are not known. By using the nose to study the
      inflammatory response possible abnormalities can be investigated carefully and
      pathophysiology of specific airway hyper-reactivities can be better understood.
      Other factors than merely constriction of the bronchial smooth muscles can cause
      narrowing of the free lumen to airflow. Functionally different and very distinct
      mucosal end-organ reactivities may also be increased. If these reactivities can
      be well assessed, specific airway hyper-reactivity can be defined. In the present
      report, specific mucosal end-organ hyper-reactivities in the allergic nasal
      mucosa are presented. Certain widespread hypotheses, such as the role of the
      eosinophil and the "increased absorption permeability theory", are disputed.

PMID- 7734973
TI  - Nonallergic rhinitis. Pathophysiology and models for study.
AB  - Nonallergic rhinitis is a diagnosis of exclusion which is given to patients who
      suffer perennial nasal congestion, rhinorrhea, and/or sneezing with no
      identifiable allergic etiology. Because there is still no clear understanding of
      the pathophysiology, it is possible that a number of different disease processes
      may be included within this clinically defined entity. This report does not
      attempt to present an overall discussion of the clinical approaches to patients
      with nonallergic rhinitis. Instead, an outline is presented of various research
      approaches which may be used in its study. A number of nasal provocation models
      using nonallergic stimuli are available for application in the laboratory. These
      include intranasal methacholine challenges, intranasal histamine challenges,
      nasal inhalation of cold dry air, and intranasal capsaicin challenges. These
      models provide certain insights into mechanisms of nonallergic hyper
      responsiveness. An additional approach to the study of nonallergic rhinitis is to
      examine available therapies, allowing the clinician to evaluate various pathways
      of importance in the disease process. These approaches provide a certain
      understanding of this common but perplexing entity, although further study is
      still required.

PMID- 7734974
TI  - Concentrations of chemical mediators in nasal secretions after nasal allergen
      challenges in atopic patients.
AB  - By using a microsuction technique, a quantitative determination of chemical
      mediators in nasal secretions was performed in 18 hay-fever patients and in a
      control group of 10 healthy volunteers. The authors then compared these
      quantitative data for mediators with objective nasal findings counting the number
      of sneezes, passive anterior rhinomanometry (PAR) and nasal inspiratory peak
      flow. A sampling protocol was designed with a follow-up of 3 days after nasal
      allergen challenge (NAC) in order to investigate both early and late allergic
      reactions. Median baseline concentrations of five major mediators were obtained:
      histamine, 19 ng/g; leukotriene C4 (LTC4), 5.7 ng/g. tryptase, 0; prostaglandin
      D2 (PGD2), 477 pg/g; eosinophil cationic protein (ECP), 105 ng/g. Significant
      increases in histamine (214 ng/g), LTC4 (20 ng/g) and tryptase (28 microU/g) were
      found, but a significant decrease occurred in ECP (47 ng/g) and PGD (226 pg/g)
      immediately after NAC in the patients studied. Most ECP concentrations (94%)
      increased slowly 1 h after NAC and reached a significantly higher level 24 h
      later. In evaluating nasal symptoms, sneezes were present in a high percentage of
      cases (76%) during the early phase but were uncommon during the late phase (29%).
      Total nasal obstruction occurred in 94% during the early phase. In contrast,
      unilateral nasal obstruction presented in 82% during the late phase, whereas
      total nasal obstruction was present only in 41%. The most common type of late
      phase nasal obstruction shown by PAR was alternating nasal obstruction.

PMID- 7734975
TI  - Implicating adhesion molecules in nasal allergic inflammation.
AB  - Allergic rhinitis is now considered an inflammatory disorder where many leukocyte
      types, including eosinophils and T-lymphocytes, accumulate in increased numbers.
      Along with mast cells and other cells, they release a wide variety of mediators,
      cytokines, and granule constituents that can directly cause inflammation or
      activate the local vascular endothelium to further enhance the recruitment of
      leukocytes through the expression and function of adhesion molecules. While the
      understanding of the importance of leukocyte and endothelial adhesion molecules
      is still at a very early stage, recent evidence has already begun to implicate
      these cell surface molecules in the pathogenesis of allergic diseases such as
      rhinitis and asthma. Additional studies, including the use of adhesion molecule
      antagonists when available, will clarify the importance of these structures in
      the pathophysiology of these disorders.

PMID- 7734976
TI  - Elevated levels of interleukins IL-1 beta, IL-6 and IL-8 in naturally acquired
      viral rhinitis.
AB  - We studied the cytokines IL(interleukin)-1 beta, IL-4, IL-6 and IL-8 in nasal
      lavage samples from 20 patients with naturally acquired viral rhinitis and 5
      healthy controls without nasal complaints. IL-1 beta, IL-6 and IL-8 levels in
      lavage fluid from the viral rhinitis patients were significantly elevated when
      compared to control subjects. IL-4 was not measurable in any of the samples. The
      cytokine levels in secretions from the healthy controls remained stable
      intraindividually on 5 consecutive sampling days. We suggest that cytokines such
      as IL-1 beta, IL-6 and IL-8, but not IL-4, are involved in the pathophysiology of
      the common cold.

PMID- 7734977
TI  - New insights into the mechanisms of immunotherapy.
AB  - Allergen-specific immunotherapy retains a place in treatment in patients with
      allergic rhinitis who fail to respond to conventional treatment with
      antihistamines and topical corticosteroids. Studies on mechanisms of
      immunotherapy have previously focussed on changes in serum antibodies, including
      blunting of seasonal rises in specific IgE and increase in "blocking" specific
      IgG antibodies. Immunotherapy in patients with rhinitis has also been shown to
      inhibit effector cells with a decrease in nasal mucosal eosinophils and
      epithelial mast cells. Recent evidence suggests that these events may be
      orchestrated by an effect of immunotherapy on T lymphocytes with alteration from
      a predominant "Th2" response (interleukin 4 and 5) in favour of an additional
      "Th1" response (gamma interferon) which may decrease tissue eosinophilia and
      local IgE production. Novel therapeutic approaches to allergic diseases might
      include use of topical gamma interferon, immunosuppressive agents, anti-CD4
      antibodies or strategies directed specifically against IL-4 or IL-5.

PMID- 7734978
TI  - Progress in the drug management of allergic rhinitis.
AB  - The diagnosis of allergic rhinitis is based on the case history, rhinoscopy and
      allergy testing. Therapy consists of allergen avoidance, pharmacotherapy,
      immunotherapy and/or surgery. This review deals only with pharmacotherapy, since
      there has been significant progress in this area. The first advance was the
      introduction of topical nasal steroids in the mid-1970s and the second the
      introduction of the second generation of H1 antihistamines in the early 1980s.
      The task for future developments is to optimize therapy by rational and combined
      use of available drugs, especially the steroid sprays and non-sedating
      antihistamines. A systematic approach to the choice of drug for the treatment of
      rhinitis is presented.

PMID- 7734979
TI  - Immunocompetent cells of the upper airway: functions in normal and diseased
      mucosa.
AB  - Secretory immunity is central in primary defense of the airway mucosa. B cells
      involved in this local immune system are initially stimulated in mucosa
      associated lymphoid tissue, including tonsils and adenoids, and then migrate to
      secretory effector sites where they become immunoglobulin (Ig)-producing plasma
      cells. Locally produced Ig consists mainly of J-chain-containing dimers and
      larger polymers of IgA (pIgA) that are selectively transported through glandular
      cells by an epithelial receptor called secretory component or pIgR. Secretory
      antibodies perform surface protection by immune exclusion of soluble antigens as
      well as infectious agents. IgG can also participate in this primary defense
      because it reaches secretions by passive diffusion similar to IgE. However, the
      inflammatory properties of antibodies belonging to the latter two classes explain
      their involvement in mucosal immunopathology when elimination of penetrating
      antigens is unsuccessful. T helper (Th) cells activated in this process may by a
      Th2 profile of cytokines promote persistent inflammation with extravasation and
      priming of eosinophils. This mechanism appears to occur in the late-phase
      allergic reaction, perhaps driven mainly by interleukin-4 (IL-4) released from
      mast cells subjected to IgE-mediated degranulation. Eosinophils are potentially
      tissue-destructive cells, particularly after priming with IL-5. Cytokines also up
      regulate adhesion molecules on vascular endothelium and epithelium, thereby
      enhancing migration of eosinophils and other leukocytes into the mucosa.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7734980
TI  - [Mycobacterial pathology in HIV infection].

PMID- 7734981
TI  - [Quo vadis Romanian pneumophthisiology?].

PMID- 7734982
TI  - [Speleoplasty, a possible alternative in the surgical treatment of cavitary
      pulmonary tuberculosis].
AB  - Speleoplasty is a method of surgical treatment of cavitary pulmonary
      tuberculosis. The proposed surgical procedure differs from thoracoplasty and from
      pulmonary resection by a direct approach of the pulmonary cavernae. Speleoplasty
      is a simple, reliable technique, reducing significantly the surgical time as well
      as the operatory and post-operatory strike risks. This procedure does not
      diminish the respiratory surface and preserves the architecture of the thorax
      wall by keeping the anatomical integrity of the pulmonary parenchyma and of the
      thorax.

PMID- 7734983
TI  - [The etiological profile of the pulmonary manifestations in AIDS patients
      (studies of 65 cases recorded in Romania up to 1 March 1993)].
AB  - HIV infection and its final form as AIDS were ignored by the public opinion in
      Romania till 1990. Nowadays it is real fact in our country. Out of total number
      of 2235 AIDS cases declared till March 1st 1993 by the Ministry of Health only
      134 were adult persons. The study concerns 65 cases of AIDS in adults in order to
      find out the lung symptoms proportion as etiologic features, to settle the ways
      of transmission of HIV infection and to warn the romanian pneumologists on this
      problem. The study shows that in 56.9% of total cases, lung symptoms were noted
      and in 49.2% the lung disease revealed the AIDS. Out of the total number of 65
      cases, 24.6% showed tuberculosis as a first disease, 12.4% lung pneumocystosis,
      7.76 Kaposi syndrome with lung expression and 4.5% other pneumopathies.

PMID- 7734984
TI  - [Nonspecific bronchial provocation with histamine and methacholine].
AB  - The inhalational histamine and metacholine test is a standard procedure to
      estimate the degree of bronchial reactivity. During the last 10 years the method
      of continuously generated aerosol inhalation compels recognition. The test
      consists in the inhalation during 2 minutes, every 5 minutes of a double dosage
      of drug followed by measurement of MEVS after each step. Thus the dosage response
      curve is set up. The concentration of the necessary drug dosage for decreasing
      with 20% of MEVS (PC20 or PD20) are accepted as indices for bronchial reactivity.
      The method is indicated in cases suspected for atypical bronchial asthma,
      professional asthma and drug research. The technical and subjective factors
      interfering the measurements should be taken into account and analysed in order
      to ensure reproducibility and comparability of the method.

PMID- 7734986
TI  - [Pleural involvement in Rustitskii-Kahler disease (a clinical case report)].
AB  - The author presents a case with pleural effusion expressing a secondary pleural
      involvement in Rustitzki-Kahler disease during a solitary plasmocytoma of the 8th
      rib. Biologically the monoclonal protein was an IgM, a rather seldom met
      evolution of myeloma. Blood electrophoresis and immunoelectrophoresis
      modifications were reflected in the pleural fluid too. The case stresses the
      difficulties met in the etiological diagnosis of pleurisies.

PMID- 7734985
TI  - [Pulmonary hamartomas--apropos 3 clinical cases].
AB  - The study starts with presentation of present day knowledge of the disease. Its
      features are predominantly X-ray images consisting mainly in a round or ovular,
      usually solitary formation ("coin lesion"). The clinical expression of the
      disease is usually very discrete, the general state unmodified. The X-ray
      evidencing follows a routine examination. 3 cases of personal observations are
      presented. All cases were solved by surgery, by removal of tumour. Etiology is
      fixed by histological examination of surgery specimen. All aspects risen by the
      differential diagnosis are largely discussed focusing on lung granuloma (e.g.
      tuberculoma) lung abscess, limited pneumonia, lipoid pneumonia a.o. Hamartomas
      are of mesenchymal origin, they are not considered just as tumours but very
      similar to "tumour-like", without invasive evolution.

PMID- 7734987
TI  - [The incidence of tuberculosis in Romania in 1993].
AB  - The situation of tuberculosis in Romania has been progressively deteriorated
      since 1986. Using the data from the TB notification forms and demographic data
      for the number of inhabitants by sex and age groups in various districts in 1993,
      there have been calculated the main TB epidemiometric indicators for 1993. TB
      notification rate in 1993 in Romania (89.4%000) is plotted against values in
      other countries of the Europe Region WHO in figure 1 and against the mean values
      for in the six WHO regions in figure 2; the dynamic of the annual values 1991
      1994 in the 41 districts of Romania are presented in figure 3 and a comparison of
      the annual values 1985-1993 in Romania versus other countries with rising values
      (USA, Denmark and Lithuania) in figure 4. Data concerning TB notification rate in
      children (20.7%000 in 1993) and its dynamic during the last 8 years is presented
      in table II, high values districts in table III, the prevalence of sources in
      tables IV and the TB mortality (10.1%000 in 1993) and its trend during the last
      11 years in table V. A series of 8 annexes presents 1993 data on TB notification
      number and rate by disease localisation, bacteriologic confirmation and sex, for
      each of the 41 districts of the country. All data are meant to reveal the
      magnitude of "TB problem" in Romania, to allow optimisation of the main control
      actions and planning of the necessary means.

PMID- 7734988
TI  - Stress and family physicians. Solutions and strategies.

PMID- 7734989
TI  - Screening for chlamydial infection. Taking stock.

PMID- 7734990
TI  - Whiplash legitimized by clinical support.

PMID- 7734991
TI  - Whiplash injuries increase with seatbelt use.

PMID- 7734992
TI  - CFPC alternate funding model.

PMID- 7734993
TI  - Young family physicians support hospital-based activities.

PMID- 7734994
TI  - Radiology rounds. Osteochondroma.

PMID- 7734995
TI  - Dermacase. Malignant lentigo.

PMID- 7734996
TI  - Screening guidelines for Chlamydia trachomatis infection. Evaluating physician
      awareness, agreement, and use.
AB  - OBJECTIVE: To assess whether physicians were aware of, agreed with, and followed
      the "1989 Canadian Guidelines for Screening for Chlamydia Trachomatis Infection
      "as they applied to screening asymptomatic women. DESIGN: A survey consisting of
      direct questions and case scenarios was scored according to the responses given
      in the guidelines. SETTING: Six hospital family practice teaching units in
      downtown Toronto. PARTICIPANTS: Of 153 staff physicians and residents surveyed
      (all staff and residents registered with the Department of Family and Community
      Medicine of the University of Toronto for the 1990-1991 academic year), a
      volunteer sample of 118 responded to a questionnaire through the mail. MAIN
      OUTCOME MEASURES: Reported awareness, agreement, and use of C trachomatis
      guidelines for screening asymptomatic women were analyzed using frequency
      distributions and cross-tabulations. RESULTS: Most (69%) respondents were unaware
      of the guidelines. Of those who were aware, 46% agreed with the guidelines and
      39% claimed to follow the guidelines. Staff physicians appeared to be more aware
      of guidelines than family medicine residents (P = 0.0175, psi 2 = 11.98); P
      values less than 0.05 were considered statistically significant. There was no
      statistically significant association between total scores and physicians'
      reported awareness of guidelines (P = 0.2287, psi 2 = 4.321). CONCLUSIONS: Most
      physicians in the sample were unaware of the guidelines. Of physicians who
      reported awareness of the guidelines, less than half agreed with or routinely
      followed them. Better methods of influencing physician behaviour must be
      developed before more guidelines are designed and distributed.

PMID- 7734997
TI  - Identifying patients with hypercholesterolemia. More than one blood sample is
      needed.
AB  - OBJECTIVE: To compare the use of one and two blood samples for diagnosing
      hypercholesterolemia DESIGN: A test-retest substudy conducted as part of a
      randomized control trial designed to compare the effectiveness of different
      counseling strategies for lowering serum cholesterol, dietary fat, and dietary
      cholesterol in patients with moderate hypercholesterolemia. SETTING: Thirty urban
      family practices. PARTICIPANTS: One hundred forty-two patients provided two blood
      samples for total cholesterol (TC) level determination at two different times
      (test results were being used as an eligibility criterion for enrollment in the
      main trial). MAIN OUTCOME MEASURES: Number of subjects correctly classified to
      cholesterol risk category (normal < 6.2 mmol/L; moderate 6.2 to 6.9 mmol/L; high
      > 6.9 mmol/L) on the basis of one TC value and on the average of two TC values.
      RESULTS: Overall misclassification rate on initial TC level was 22.5%. Overall
      false-positive rate was 19.0%, but false-positive rate for those initially
      assigned to the high category was 50%. Overall false-negative rate was 3.5%.
      Misclassification rates did not differ statistically on the basis of age, sex,
      blood pressure, smoking status, family history of coronary heart disease,
      presence of diabetes, obesity, the laboratory used, or whether the patient had
      fasted before giving blood. CONCLUSIONS: Single TC levels are too unreliable for
      diagnostic purposes, even if the subjects fast before testing. Family physicians
      should base their treatment decisions on the average of two cholesterol readings
      taken at different times 1 to 8 weeks apart.

PMID- 7734998
TI  - Helping physicians in distress. Developing a physician assessment and referral
      service.
AB  - In 1987, a Physician Assessment and Referral Service was created in the
      Department of Family Medicine of a large urban hospital to help physicians and
      their families. This article describes the rationale, development,
      accomplishments, and limitations of the service in light of 5 years' experience.
      Although this program was developed for family physicians in particular, it has
      value for all medical specialties.

PMID- 7734999
TI  - Physician, heal thyself. Developing a hospital-based physician well-being
      committee.
AB  - This article describes the development of a physician well-being committee at the
      Sir Mortimer B. Davis-Jewish General Hospital. It discusses the issue of
      physician stress, outlines the committee's mandate, and describes the various
      activities and services that were implemented.

PMID- 7735000
TI  - Illness as lifestyle.
AB  - To appreciate what illness means to an individual, physicians must understand
      that person's attitudes, views, and style of life. People react uniquely and
      creatively to illness and disability. Some incorporate the illness into their
      lives and use it to help them achieve goals that might not be obvious to the
      doctor. A case study presents diagnostic and therapeutic problems familiar to
      family physicians.

PMID- 7735001
TI  - Group B streptococcus. Is it time for a screening program?
AB  - Group B streptococcal infection often causes perinatal sepsis. Early diagnosis is
      based on a high index of suspicion and laboratory tests. Proposed interventions
      targeted at the antepartum, intrapartum, and postpartum periods have met with
      limited success. Screening has not been widely adopted.

PMID- 7735002
TI  - Androgen action: molecular mechanism and medical application.
AB  - Androgen action in many organs, such as prostate and skin, is dependent on the
      conversion of testosterone by 5 alpha-reductase to 5 alpha-dihydrotestosterone. 5
      alpha-Dihydrotestosterone then binds to the androgen receptor to regulate
      specific gene expression. Inhibitors of 5 alpha-reductase are useful for the
      selective treatment of prostatic cancer, benign prostate hyperplasia, acne,
      baldness and female hirsutism, without affecting spermatogenesis, sexual behavior
      and smooth muscle growth, that do not require the conversion of testosterone to 5
      alpha-dihydrotestosterone. Certain unsaturated fatty acids, such as gamma
      linolenic acid, are potent 5 alpha-reductase inhibitors, suggesting a linkage
      between unsaturated fatty acids and androgen action. Mutations in androgen
      receptor genes are responsible for many cases of androgen-insensitivity. In some
      prostate cancer cells, some antiandrogens may act like androgens in stimulating
      the proliferation of the cancer cells because these antiandrogens can bind to a
      mutated androgen receptor and transactivate target genes. Prostate cancers are
      usually androgen-dependent initially but can lose dependency and responsiveness.
      Tumor cells which are resistant to endocrine therapy ultimately proliferate.
      Androgen-independent or androgen-repressive cells can arise from androgen
      sensitive prostate cancer cells by changes in specific gene expression over time
      in a clonal isolate. This change in androgen responsiveness was accompanied by a
      change in androgen receptor expression and transcriptional activity as well as
      expression of some oncogenes.

PMID- 7735003
TI  - Feasibility and effectiveness of a stages-of-change model in cigarette smoking
      cessation counseling.
AB  - Counseling coupled with a stages-of-change model in cigarette smoking cessation
      is a useful method for physicians to help patients stop smoking. The participants
      were 27 physicians, randomly assigned to three groups of nine physicians each.
      The first group of physicians were given two lectures on the stages-of-change
      model on which to base their patient counseling. The second group of physicians
      were not exposed to the model but a reminder reading "Ask your patients to stop
      smoking" was placed in their clinic. The third group of physicians were neither
      exposed to the model nor given any reminder. Of the 93 smokers among the patients
      of the 27 physicians, 39 were in the first group, 26 in the second, and 28 in the
      third. A survey indicated that among the three groups there was no significant
      difference in demographic data, cigarette smoking history, and personal attitude
      toward smoking cessation counseling. At the end of six months, the first group of
      patients accomplished a quit smoking rate of 28.6%; of the patients still smoking
      56% had decreased their daily cigarette consumption. The corresponding figures
      for the second group were 8.3% and 9.1%. The corresponding figures for the third
      group were 4.3% and 13.6%. These data show that counseling coupled with the
      concept of a stages-of-change model is feasible and effective to assist with
      cigarette smoking cessation.

PMID- 7735004
TI  - Utilization and sources of blood components in Taiwan.
AB  - A three-year survey program, sponsored by the Department of Health, Taiwan
      R.O.C., was conducted from 1990 to 1992 to investigate blood utilization and
      blood sources in Taiwanese hospitals. The survey covered the period from January
      1989 to December 1991. The hospitals surveyed included nine to 12 medical
      centers, 40 to 48 regional hospitals, 148 to 163 community hospitals, and 363 to
      451 specialty hospitals. Their respective response rates for three consecutive
      years were 75.0%, 87.9% and 84.1%. Approximately 86% (for 1988) to 98% (for 1991)
      of all units transfused in Taiwan were surveyed (unit of blood = 250 ml).
      Utilization of various blood components, ie, red blood cell (RBC) components,
      frozen plasma (FP), cryoprecipitate (CRYO) and platelets (PLT), showed a trend of
      continuous increase. In 1991, 12 medical centers and 48 regional hospitals
      consumed 81.4% of the RBC components, including whole blood (WB) and packed red
      blood cells (PRBC), while the remaining 18.6% was consumed by 138 community
      hospitals and 282 specialty hospitals. The average blood utilization of medical
      centers was 37,383 units of RBC components, 30,949 units of FP, 6,990 units of
      CRYO, and 21,353 units of PLT per hospital. Utilization of RBC components was
      7,191 units per regional hospital, 1,012 units per community hospital, and 148
      units per specialty hospital. In 1991, almost all other components consumed in
      Taiwan, namely FP, CRYO and PLT, were utilized by medical centers and regional
      hospitals. WB and PRBC sources showed a drastic decline in paid donation, a
      modest decrease in hospital blood drawn from voluntary donors and an increasing
      role of the BLood Donation Association (BDA) in volunteer blood
      donation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735005
TI  - Carrier screening and prenatal diagnosis for alpha-thalassemia with biphasic
      polymerase chain reaction.
AB  - Alpha-thalassemia is the most common single gene disorder in Taiwan and Southeast
      China. The majority of alpha-thalassemic mutations in this area are alpha
      thalassemia 1. Homozygous alpha-thalassemia 1 has been recognized as the most
      important cause of hydrops fetalis. To investigate the incidence of alpha
      thalassemia 1 mutations and to characterize its molecular defects, cord blood
      electrophoresis was performed on 2,000 newborns, of which 99 (5%) cases were
      found to have hemoglobin (Hb) Bart's levels > 3.0%. A methodology using biphasic
      polymerase chain reaction (PCR) with nesting primers was developed to
      characterize the alpha-thalassemia 1 Southeast Asia type (SEA) deletion in the
      cases with detectable Hb Bart's levels. The SEA deletion was found in 92 (93%) of
      99 cases. Prenatal screening was performed on couples with abnormal hematologic
      indices, and PCR was used to detect couples heterozygous for SEA deletion.
      Prenatal diagnosis was performed in 21 cases, and four cases were found to have a
      homozygous SEA deletion. This strategy can be applied to couples who need
      prenatal genetic counseling for alpha-thalassemia major in this area.

PMID- 7735006
TI  - Human dermal papilla cells and outer root sheath cells: no follicular
      differentiation in nude mice and chicken embryos.
AB  - Human scalp specimens were incubated in 5 U/ml dispase solution at 4 degrees C
      overnight before the isolation of dermal papillae and follicle epithelium. This
      pretreatment not only facilitated the attachment and cell outgrowth of dermal
      papillae but also made it easier to pluck out hairs with intact follicle
      epithelium. The outer root sheath cells were released from the follicle
      epithelium and grown on a feeder layer of mitomycin C-treated human dermal
      fibroblasts. The subcultured outer root sheath cells were grown in a serum-free
      medium. When the mixtures of early-passage dermal papilla cells and outer root
      sheath cells were injected into the subcutis of nude mice, an epidermal cyst
      surrounded by layers of fibrous tissue was found in three weeks. No hair
      follicles were found when the mixtures were implanted onto the chorioallantoic
      membrane of nine-day-old chicken embryos. A keratinized mass lying on the
      chorionic epithelium with or without smaller similar masses in the
      chorioallantoic membrane was found in eight days. No hair follicle-like structure
      could be found. Possible factors contributing to the failure to undergo
      follicular differentiation in this study are discussed.

PMID- 7735007
TI  - Evaluation of immunosuppressive acidic protein in human ovarian cancer.
AB  - This study was conducted to determine the levels of serum immunosuppressive
      acidic protein (IAP) in Chinese female controls and patients with ovarian tumors;
      and to examine the usefulness of serum IAP as an additional diagnostic test for
      ovarian cancer. Serum IAP was determined by a single radial immunodiffusion
      method. Blood samples were collected prior to surgery from patients with ovarian
      tumors and from female controls. A histologic diagnosis was made, and staging was
      performed on the basis of the FIGO staging system for ovarian cancer. The studied
      subjects included 33 healthy controls, 33 patients with benign ovarian tumors and
      32 patients with ovarian cancer (stage I-III, and recurrent). The data were
      analyzed by Student's t test, Fisher's exact test and the one-way ANOVA test. The
      mean (+/- SD) level of serum IAP in controls was 330 +/- 61 micrograms/ml. The
      calculated normal upper limit (mean plus 2 SD) was 452 micrograms/ml. The mean
      value (867 +/- 392 micrograms/ml) in ovarian cancer was significantly higher than
      the controls (p < 0.001) or the benign ovarian tumors (333 +/- 95 micrograms/ml)
      (p < 0.001). Five (15.6%) of 32 patients with ovarian cancer had false-negative
      results. Three (9.1%) of 33 patients with benign ovarian tumors showed false
      positive IAP levels. The pathologic diagnosis of these three patients revealed
      that two had endometrioma and one had mucinous cystadenoma with hemorrhagic
      necrosis. Three of four patients with epithelial ovarian cancer of borderline
      malignancy had IAP levels only slightly higher than the cut-off point of 452
      micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735008
TI  - Acetabular allograft reconstruction in total hip arthroplasty: preliminary report
      with clinical, roentgenographic and scintigraphic analyses.
AB  - From January 1986 to June 1991, we used structural allografts to augment major
      acetabular deficiencies during primary or revision total hip arthroplasty (THA)
      in 54 patients. Forty-four patients (46 hips) with a minimal follow-up of two
      years were reviewed. The average patient age was 50.2 years. The diagnosis was
      loose THA component in 36 hips, six failed Austin-Moores, three septic hip
      sequelae, and one failed bipolar hemiarthroplasty. Their preoperative hip ratings
      (modified d'Aubigne and Postel rating system) averaged 10.7 points. Forty-five
      allografts (98%) united roentgenographically with an average union period of 11.8
      months. Five acetabular components (10.9%) developed aseptic loosening; one of
      them underwent revision using a healing allograft and one hip needed further
      acetabular reconstruction with allograft due to complete necrosis of the original
      allograft. One additional hip required resection arthroplasty for septic
      loosening. The 43 surviving hips had a mean hip score of 16.7 points at the
      latest follow-up. Radiographic evidence of graft resorption was seen in eight
      hips, which was not correlated with acetabular loosening. Serial single photon
      emission computed tomography (SPECT) study was employed postoperatively in 20
      patients (21 hips) to assess the healing process and graft viability. Seven
      allografts (33.3%) were nonviable on serial SPECT studies, while 14 allografts
      (66.7%) were viable. The compatibility of host-donor A, B, O blood typing and the
      use of cement did not correlate with allograft viability. Allograft viability did
      not contribute to the failure of cup components. Considering the major acetabular
      deficiency and the absence of sufficient autograft material, the use of frozen
      allografts appears to be justified.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735009
TI  - Differential effects of nitric oxide synthesis inhibitor on rat diaphragmatic
      microcirculation under basal conditions and after vasodilator stimulation.
AB  - To assess the effect of endothelium-derived relaxing factor (EDRF) on the
      diaphragmatic microcirculation under basal conditions and after vasodilator
      stimulation, prepared diaphragms from anesthetized rats were studied. With
      bicarbonate-buffered Ringer's solution suffusing the diaphragm, the
      microcirculatory blood flow was recorded by laser-Doppler flowmetry (QLDF). Drugs
      were applied to the surface of the diaphragm. Five series of experiments were
      performed. In Series 1, the effects of acetylcholine (ACh, 10(-4) M) and sodium
      nitroprusside (SNP, 3 x 10(-6) M) were measured before and after 15 minutes
      suffusion of N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M). Trend
      analyses revealed that the vasodilator effect of SNP was not affected, while that
      of ACh was abolished by L-NAME. In Series 2, both ACh and SNP elicited a
      concentration-dependent increase in QLDF. In Series 3, following 15 minutes
      suffusion with L-NAME (10(-4) M), there was no change in baseline QLDF and the
      ACh-induced QLDF change was abolished, while the effect of SNP was maintained. In
      Series 4, five minutes of pretreatment with L-arginine (L-arg, 10(-2) M),
      followed by co-administration of L-arg (10(-2) M) and L-NAME (10(-4) M) for
      another 15 minutes, did not prevent the inhibitory effect on ACh-induced QLDF
      change by L-NAME. In Series 5, 20 minutes application of L-arg (10(-2) M) alone
      did not affect baseline QLDF. Also, L-arg did not influence the ACh-induced
      vasodilating response, whereas it slightly increased the SNP-induced vasodilating
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735010
TI  - Tuberous sclerosis associated with neurofibromatosis: report of a case.
AB  - Neurofibromatosis and tuberous sclerosis are phakomatous syndrome diseases. They
      are both inherited as autosomal dominant diseases. Neurofibromatosis type 1 and
      tuberous sclerosis very seldom occur together. We report a 16-year-old male who
      had characteristics of these two diseases. This patient had all the criteria for
      a definitive diagnosis of tuberous sclerosis such as: classical shagreen patches,
      periungual fibroma, retinal hamartomata, facial angiofibroma, renal
      angiomyolipomata, and subependymal glial nodules on computed tomography. He also
      had the three presumptive diagnostic criteria: cardiac rhabdomyoma, seizure
      history and first degree relatives with tuberous sclerosis. The patient had more
      than six cafe-au-lait spots, the greatest diameter of which exceeded 15 mm in
      diameter. Multiple neurofibromas, one plexiform neurofibroma, axillary freckling
      and optic gliomas were also found on his body. These criteria are sufficient for
      a diagnosis of neurofibromatosis type 1 to be made. The skin biopsies were also
      consistent with the disease. Apart from the patient's mother and younger sister,
      who had tuberous sclerosis, there was no other person with neurofibromatosis type
      1 in his immediate family. We believe that tuberous sclerosis was inherited from
      his mother and that neurofibromatosis type 1 may have resulted from mutation.

PMID- 7735011
TI  - Fracture of the posterior process of the talus associated with subtalar
      dislocation: report of a case.
AB  - Although subtalar dislocation is not common in foot trauma, fracture of the
      entire posterior process of the talus is even rarer. The concomitant injury of a
      subtalar dislocation associated with a fracture of the posterior process of the
      talus has not yet been reported in the medical literature. A 52-year-old woman
      involved in a traffic accident had her right foot twisted into an inversion
      deformity. An X-ray revealed a medial subtalar dislocation associated with a
      fracture of the entire posterior process of the talus. Tomography demonstrated
      that the posterior process was incongruent to the ankle and the subtalar joints.
      The subtalar dislocation was treated with a closed reduction. The fracture of the
      posterior process was treated with an open reduction and internal fixation. After
      the anatomic reduction of both injuries, the patient recovered and returned to
      her previous activities.

PMID- 7735012
TI  - A case of Graves' diseases associated with intracranial moyamoya vessels and
      tubular stenosis of extracranial internal carotid arteries.
AB  - A 28-year-old woman presented with a clinical picture of hyperthyroidism, goiter,
      ophthalmopathy, and an ensuing ischemic stroke. Cerebral angiography demonstrated
      moyamoya vessels around the Willis's circle and tubular stenosis of the bilateral
      extracranial internal carotid arteries. The combination of the above angiographic
      abnormalities occurring in a patient with Graves' disease is extremely rare. A
      pathogenic link between Graves' disease and certain specific vascular disorders
      is suspected.

PMID- 7735013
TI  - Insulin-like growth factor-I in children with short stature.
AB  - The purpose of this study was to evaluate the clinical application of serum
      insulin-like growth factor-I (IGF-I) levels for the workup of prepubertal
      children with short stature. IGF-I serum levels were measured by radioimmunoassay
      in 92 short prepubertal children (55 normal-short children, 18 dysmorphic-short
      children, and 19 children with classical growth hormone deficiency) and 105
      normal prepubertal children. The serum IGF-I levels (mean +/- SEM) in these three
      groups of short children were 160 +/- 9 ng/ml, 188 +/- 16 ng/ml and 26 +/- 3
      ng/ml, respectively. The mean serum IGF-I level for the 105 normal prepubertal
      children was 160 +/- 7 ng/ml. The mean serum IGF-I levels of the first two groups
      of short children were not significantly different from that of the prepubertal
      children with normal stature. On the other hand, the mean serum IGF-I level in
      children with classical growth hormone deficiency was significantly lower than
      those of the other two groups of short children and that of prepubertal children
      with normal stature. Our study shows that the determination of serum IGF-I levels
      is of clinical value in the evaluation of short prepubertal children.

PMID- 7735014
TI  - Incomplete forms of Beckwith-Wiedemann syndrome: report of a case.
AB  - Beckwith-Wiedemann syndrome is a rare disease characterized by a constellation of
      congenital and time-dependent abnormalities such as defects of the abdominal
      wall, gigantism, craniofacial dysmorphism, visceromegaly and hemihypertrophy. The
      syndrome is divided into complete and incomplete forms and, as it may only have
      subtle phenotypic features, it is easily neglected by clinicians. Patients with
      this syndrome, particularly those associated with hemihypertrophy, have a high
      risk of growing malignant tumors. This is a case report of a patient with an
      incomplete form of this syndrome with left hemihypertrophy, hepatosplenomegaly
      and a small right adrenal cystic lesion.

PMID- 7735015
TI  - Elevated serum CA-125 in tuberculous peritonitis: report of a case.
AB  - A 37-year-old female presented with a 2-month history of abdominal distention.
      Omentum masses with massive ascites were found and ovarian cancer with peritoneal
      carcinomatosis was suspected. Her serum CA-125 level was over 500 U/ml before
      therapy. Tuberculous peritonitis was diagnosed via peritoneal biopsy. The serum
      CA-125 level returned to normal after antituberculous therapy. Elevated serum CA
      125 does not always indicate ovarian malignancy. This tumor marker may be used to
      monitor the disease activity in non-neoplastic ascitic states.

PMID- 7735016
TI  - Alcohol amnesia.

PMID- 7735017
TI  - A review of the literature examining the relationship between alcohol use and HIV
      related sexual risk-taking in young people.
AB  - Young people have been targeted as a potentially vulnerable population for the
      spread of HIV. The influence of alcohol on sexual behaviour is part of popular
      knowledge. More recently, studies have attempted to illuminate the relationship
      between alcohol use and sexual risk-taking in relation to HIV transmission. In
      our review of the literature three important points are highlighted for
      researchers in this area. First, methodological problems make establishing any
      relationship extremely difficult. Secondly, the concept of sexual risk-taking has
      to be developed to include acknowledgement of the context in which sex takes
      place rather than defining risk only in terms of sexual acts. Finally,
      populations of gay men and men who have sex with men and lesbians are
      sufficiently different from heterosexuals, with regard to the influence of
      alcohol on sexual behaviour, to make generalizations about one population
      inappropriate for the other.

PMID- 7735018
TI  - The Community Epidemiology Laboratory: studying alcohol problems in community and
      agency-based populations.
AB  - This paper describes the Community Epidemiology Laboratory (CEL) of the Alcohol
      Research Group, a project focusing on the epidemiology of alcohol problems and
      community responses to those problems. Since 1980, a series of probability
      surveys have been conducted in the general population and in a wide range of
      health and social service agencies in a northern California county. The agency
      based samples have included all agencies or representative samples of each system
      (alcohol treatment, drug treatment, mental health treatment, emergency rooms,
      primary health care, criminal justice and welfare) with probability samples of
      clients interviewed at intake. These studies have addressed questions regarding
      (1) the burden and epidemiologic description of alcohol problems in a community;
      (2) the relationship of alcohol to other health and social problems; (3) the
      influence of social policy on the constitution of services and care of
      individuals; and (4) health services issues of access and pathways to treatment.
      The project is designed for comparable analysis of studies with special focus on
      women and ethnic minorities. This paper provides an overview of the CEL,
      including its major research questions, overall design, sampling principles,
      methodological issues and measures. It highlights the main findings and discusses
      the limitations and advantages of such methodologies for further understanding
      alcohol problems in a community.

PMID- 7735019
TI  - Alcohol and casualties: comparison of county-wide emergency room data with the
      county general population.
AB  - A representative sample of patients in hospital emergency rooms (ERs) in a
      Northern California county (n = 3731) were compared with a household probability
      sample of those living in the same county (n = 2101). The injured in the ER
      sample were more likely to be black and under 30 than those in the general
      population sample who reported an injury during the last year which was treated
      in the ER. ER injured were more likely to be abstainers than injured in the
      general population and among drinkers, they were also more likely to report
      social consequences of drinking, but were no more likely to report experiences
      associated with alcohol dependence. Similar differences were found between the
      injured and the non-injured in the two samples, with the injured more likely to
      be male, younger, never married and to report heavy drinking, drunkenness, social
      consequences of drinking and alcohol dependence experiences. The data suggest
      that associations of alcohol and injury found in representative samples of the ER
      population may be generalizable to the injured in the general population from
      which these patients come, with differences which do exist most likely
      attributable to characteristics associated with emergency room usage.

PMID- 7735020
TI  - The association between DSM-III-R alcohol dependence, psychological distress and
      drug use.
AB  - This paper examines the association between DSM-III-R alcohol dependence,
      psychological distress and the frequency of drug use in a sample of 219 men and
      162 women consecutively admitted to nine alcohol treatment programs in a Northern
      California county. Results show that psychological distress is higher among men
      who are more severely dependent on alcohol and among those who have lower
      education; women who are less alcohol dependent and women who are younger have
      higher scores in psychological distress than other women. With regard to drug
      use, about 65% of the men and 64% of the women report using a drug other than
      alcohol at least once a week during the 12 months prior to admission into
      treatment. Among both men and women, the drugs most frequently used are
      crack/cocaine, marijuana and methamphetamine. Among men, regression analysis
      shows that drug use is associated with being younger. Among women results show
      that the predictors of drug use are being younger, being unemployed, having a
      higher income, being a heavier drinker and having fewer symptoms of alcohol
      dependence. These results show a complex pattern of association across alcohol
      dependence, drug use and psychological distress. Knowledge of this pattern is
      necessary for tailoring effective clinical interventions to clients with
      different kinds of comorbidity.

PMID- 7735021
TI  - Drinking problems and self-reported criminal behavior, arrests and convictions:
      1990 US alcohol and 1989 county surveys.
AB  - Use of general population surveys in addition to institutional samples is
      critical to disentangling the relationship between criminal behavior and alcohol
      problems or use of illicit drugs. Local area studies can be useful but
      generalizability of their results is seldom studied. Data from recent US national
      (n = 2058) and county (n = 3069) general population surveys are used to examine
      the role of alcohol problem and drug use history in predicting self-reported
      criminal behavior, arrest and conviction within a logistic regression framework.
      In the national and county surveys controlling for age, gender, income, marital
      status, employment, education, race and drug use, lifetime drinking problems
      significantly predicted current criminal behavior (odds ratios 1.3 and 1.5,
      respectively) with slightly stronger relationships noted in equivalent models
      predicting arrest (odds ratios 1.7 and 1.8) and conviction (odds ratios 1.7 and
      1.6). Relationships between alcohol, drugs and criminal behavior/justice
      variables are discussed. Parallels between US and county results suggest that
      findings from intensive, articulated analyses of community-level population and
      institutional surveys may be cautiously generalized beyond their geographic
      locus.

PMID- 7735022
TI  - The role of problem drinking in psychiatric admissions.
AB  - Although problem drinkers are over-represented in psychiatric treatment
      populations throughout the United States, it is unclear whether this is primarily
      due to difficulties in differentially diagnosing alcohol and mental problems and
      to high rates of comorbidity, or to factors unique to help-seeking for alcohol
      problems. This article examines the role that alcohol problems play in treatment
      entry to inpatient and outpatient mental health agencies, considering the
      potential roles of a drinking problem both as a condition perceived by the
      sufferer to require a psychiatrist's help, and as a source of social disruption
      that activates others to encourage mental health treatment. Analysis focuses on
      comparing samples of newly admitted patients in a community mental health system
      and untreated individuals with high levels of psychiatric symptoms living in the
      same community. Experiencing the adverse social consequences of a drinking
      problem, holding the belief that drinking has caused one's psychological
      problems, and having prior experiences in mental health treatment for a drinking
      problem are factors found to be positively associated with psychiatric
      admissions, while heavier drinking and dependence symptoms are not. Further
      analysis of events precipitating psychiatric admission suggests that an important
      role for the mental health system vis a vis alcohol problems is to contain social
      disruptions attributable to problem drinking in the community. Alcohol-related
      psychiatric admissions are found to have more frequently involved public
      disruptions, to have elicited police or court referrals, and to have more often
      resulted in the client's going to a locked hospital ward, as opposed to a mental
      health outpatient clinic.

PMID- 7735023
TI  - Assessing bias in community-based prevalence estimates: towards an unduplicated
      count of problem drinkers and drug users.
AB  - General population survey estimates of the overall prevalence of problem drinking
      and drug use in a community are biased by the exclusion of non-household
      populations. Estimates based on compiling prevalences in community institutions
      may also be biased due to over-counting of users of more than one institution.
      This paper examines prevalence estimates derived from probability samples of
      problem drinkers in the general population and within alcohol treatment, drug
      treatment, mental health, criminal justice and welfare agencies in a single US
      county. Data sets are merged and weighted to reflect a community sample of
      institutions, and a 17% subset of cases is identified within the institutional
      samples that are not living in housing units typically included in general
      population sampling frames. The difference in prevalences of problem drinking in
      the household and non-household populations is found to be large: 11% and 48%,
      respectively. Even greater differences are found between estimates of
      unprescribed weekly drug use (6% and 47%, respectively) and combined problem
      drinking and weekly drug use (2% and 27%, respectively). This suggests that
      confining samples to the household population can systematically under-represent
      the prevalence of problem drinking and drug use. A second source of bias in
      prevalence is characteristic of studies using records from multiple institutions.
      When duplication of service use in the five agency samples is considered, it
      becomes apparent that prevalence may be biased upward due to over-counting of
      multiple service users.

PMID- 7735024
TI  - Cessation of long-term nicotine gum use--a prospective, randomized trial.
AB  - Nicotine gum is an important adjunct for smoking cessation for many smokers, and
      long-term use of nicotine gum will occur in a small percentage of patients. To
      date, no method of cessation in long-term users has been studied in a randomized
      trial. We enrolled 26 subjects at the Mayo Clinic site of the Lung Health Study
      who had used nicotine gum for more than 6 months to participate in a trial where
      subjects were randomly assigned to: (1) abrupt cessation, (2) taper with placebo
      gum, or (3) taper with active gum. At the end of the 6-week trial, the percentage
      of subjects abstinent from gum use and not smoking was not different among the
      three groups: 66.7% for the abrupt cessation group, 71.4% for the taper with
      placebo gum group and 60% for the taper with active gum group. One subject in the
      taper with placebo gum group relapsed to smoking during the trial but was
      abstinent from smoking again at long-term follow-up. Long-term follow-up (median
      284 days) showed 65% of subjects were abstinent from all nicotine products.
      Motivated subjects can stop long-term nicotine gum use without relapse to gum use
      or smoking by either abrupt cessation or brief tapering.

PMID- 7735025
TI  - The impact of a brief motivational intervention with opiate users attending a
      methadone programme.
AB  - During the 1980s Motivational Interviewing emerged as one of the memes of the
      addictions field. This occurred despite the lack of scientific evidence
      supporting its utility. In this paper findings of a controlled trial of a brief
      motivational intervention with illicit drug users (n = 122) attending a methadone
      clinic are reported. Clients who met the study's inclusion criteria were randomly
      allocated to either a motivational (experimental, n = 57) or educational
      (control, n = 65) procedure. Over the 6-month follow-up period the motivational
      subjects demonstrated a greater, immediate, commitment to abstention, reported
      more positive expected outcomes for abstention, reported fewer opiate-related
      problems, were initially more contemplative of change, complied with the
      methadone programme longer and relapsed less quickly than the control group.
      There was, however, no difference in terms of the severity of reported opiate
      dependence and the control group fared better on reported self-efficacy. It was
      concluded that motivational interventions of the type investigated are useful
      adjuncts to methadone programmes.

PMID- 7735026
TI  - An indicator model of drug use in Israel.
AB  - A new methodology is proposed for measuring illicit drug activity. Factor
      analysis is used to estimate the factor score(s) that underlie the time series
      for a number of indicators that are hypothesized to be directly or indirectly
      related to drug activity. The factor score bears the interpretation of an index
      of drug activity. The methodology is implemented using data for Israel over the
      period 1950-1991. The methodology does not provide absolute measures of incidence
      or prevalence. It therefore complements rather than substitutes survey methods.
      On the other hand, it is cheap to apply, easy to update and most probably more
      objective in measurement.

PMID- 7735027
TI  - A case of nicotine psychosis?
AB  - A woman attempting to stop smoking using transdermal nicotine patches experienced
      a variety of transient delusions and hallucinations after smoking a cigarette.
      Various possible explanations are discussed.

PMID- 7735028
TI  - Alcohol policies--in poverty and in wealth.

PMID- 7735029
TI  - Alcohol policies--in poverty and in wealth.

PMID- 7735030
TI  - [The rhythm of protein synthesis in denervated rat liver].
AB  - Using the radiochemical method, we found a circahoralian rhythm of protein
      synthesis in slices of rat liver two weeks after transection of the vagus nerve
      anterior stem or bilateral subphrenic vagotomy with simultaneous transection of
      the celiac plexus hepatic branches. The rhythm was similar to those found in
      slices of normal liver or in a monolayer culture of hepatocytes. The
      incorporation of leucine in proteins and the pool of free leucine were similar in
      the denervated and normal liver. The self-synchronization of individual cell
      oscillations in protein synthesis intensity was shown earlier in experiments
      performed on cell cultures. A study of protein synthesis in the denervated liver
      suggests that cell interactions are also the main mechanism underlying the
      synchronization of oscillating cellular functions in the organ in situ.

PMID- 7735031
TI  - [The effect of irradiation at low doses on the survival of cells and their
      descendants].
AB  - We investigated the survival of HeLa cells subjected to acute and prolonged gamma
      irradiation and that of their descendants, as well as that of cells exposed in
      the accident zone around the Chernobyl' Nuclear Power Station. Radiation was
      shown to induce reproductive death in several (four) generations, as shown by the
      increased occurrence of of giant cells. The absolute effect increases with
      radiation dose.

PMID- 7735032
TI  - [Changes in the rate of protein biosynthesis in the organs of mice under the
      action of the delta sleep-inducing peptide and psychoemotional stress].
AB  - The effects of delta-sleep-inducing peptide (DSIP) and its analogs (ID-6 and ID
      12) on the protein synthesis rate in the mouse brain, liver, and spleen were
      studied with special reference to mechanisms underlying the adaptogenic action of
      DSIP. Time-related changes of the protein synthesis rate were estimated in the
      mouse organs after a single intraperitoneal injection of the peptide (120 mg/kg
      body weight) and the psycho-emotional stress with or without preliminary (1 h
      before) injection of the peptide. After DSIP administration, the protein
      biosynthesis was activated and the dynamics of stress-induced changes of
      biosynthesis were modified. The data obtained suggest that the mechanisms
      underlying the DSIP adaptogenic action involve its modulatory effect on the
      regulatory system of protein biosynthesis.

PMID- 7735033
TI  - [The effect of space flight factors on the cellular proliferative activity of
      different eye tissues during lens regeneration in the Spanish newt Pleurodeles
      waltlii].
AB  - The proliferative activity of the cells of various eye tissues was studied during
      lens regeneration in Pleurodeles waltlii under the influence of space-flight
      factors. After space-flight termination, the index of 3H-thymidine labelled
      nuclei increased reliably in the lens regenerate, in the ciliary zone of the
      iris, and in the growth zone of the retina, i.e., in the eye tissues that are not
      directly involved in formation of the regenerate cell population. The rate of
      increase in regenerate size was higher in the flight group than in the control.
      Enhancement of the proliferative activity of eye tissues, acceleration of lens
      regeneration, and the larger size of the regenerates are related to hormonal
      changes arising under the effect of space-flight factors. We propose that changes
      in calcium metabolism under the conditions of microgravity (in particular,
      increased prolactin production) accelerates the regeneration of both lens and
      limb in P. waltlii.

PMID- 7735034
TI  - [The characteristics of water metabolism and the resistance to dehydration of
      representatives of the family of mustelids (Carnivora: Mustelidae)].
AB  - Food consumption, total water intake, urine volume and concentration, and water
      content in feces were determined under the conditions of free access to drinking
      water and in its absence in some mustelids that inhabit territories with
      different water accessibility: Mustela putorius, M. eversmanni, M. lutreola, and
      M. vison. Specific features of water metabolism and resistance to dehydration in
      the studied species corresponded fairly well to differences in their ecology.

PMID- 7735035
TI  - [The use of antifreeze glycoproteins in the freezing in liquid nitrogen of early
      mouse embryos].
AB  - The cryoprotective properties of antifreeze glycoproteins (AFGPs) isolated from
      White Sea cod (Gadus morhua) blood were analyzed. Improved preservation of
      morphological characteristics was observed in two-cell mouse embryos frozen in
      the presence of AFGP but without other cryoprotectors. However, subsequent
      development after thawing was achieved only with embryos frozen in a medium
      containing both AFGP and dimethyl sulfoxide. The maximum increase in the number
      of surviving embryos (by a factor of approximately two, as compared with the
      control) was observed at AFGP and DMSO concentrations of 20 mg/ml and 25%,
      respectively.

PMID- 7735036
TI  - [The interaction of phoscarban with the esterases of houseflies and synanthropic
      cockroaches].
AB  - Interactions of phoscarban and its "oxon" with the esterase complex of the house
      fly imago and four species of synanthropic cockroaches were studied. Phoscarban
      and its oxon have a wide spectrum of effects on the esterase complex in
      cockroaches and flies. These compounds are not specific inhibitors of any of the
      zones of esterase activity. Their insecticide effect depends on their ability to
      inhibit both choline esterases, which are responsible for nervous activity, and
      carboxyl esterases, which are involved in the detoxication of these compounds. We
      studied the species specificity of the esterase complex, including individual
      types and fractions, to phoscarban and its oxon in the order Dictyoptera. It was
      especially distinct for membrane-bound and water-soluble forms of choline
      esterases.

PMID- 7735038
TI  - 12th annual ECP symposium. Gastric cancer: potential for prevention. Porto,
      Portugal, 7-8 June 1994. Proceedings.

PMID- 7735037
TI  - [An anticoagulant from extracts of peony roots: its isolation and properties].
AB  - A protein-free anticoagulant preparation displaying anticoagulative but not
      fibrinolytic activity in vitro was isolated from peony. Electrophoretic,
      chromatographic, and spectral analyses revealed that this anticoagulant resembles
      animal heparin: it contains sulfur, carbon, and nitrogen in quantities
      characteristic of the latter. Plant heparin enhances anticoagulative and
      fibrinolytic plasma properties and decreases platelet aggregation. It may be used
      as a harmless and ecologically pure anticoagulant.

PMID- 7735039
TI  - Epidemiology of gastric cancer in Portugal.

PMID- 7735040
TI  - Genotoxic flavonoids and red wine: a possible role in stomach carcinogenesis.

PMID- 7735041
TI  - Natural history of precursor lesions to gastric carcinoma: growth factors and
      oncogenes in the metaplasia-dysplasia-carcinoma sequence.

PMID- 7735042
TI  - Mechanisms of gastric carcinogenesis.

PMID- 7735043
TI  - Female sex hormone receptors are not involved in gastric carcinogenesis. A
      biochemical and immunohistochemical study.

PMID- 7735044
TI  - Glycosylation features of gastric carcinoma initiation and progression. A review
      with emphasis on simple mucin-type carbohydrates and histo-blood group antigens
      of the Lewis system.

PMID- 7735046
TI  - Epidemiology of gastric cancer in Europe.

PMID- 7735045
TI  - Oncogenes and gastric cancer.

PMID- 7735047
TI  - Mechanisms of gastric mucosal damage.

PMID- 7735049
TI  - The diagnosis of Helicobacter pylori in gastric preneoplastic and neoplastic
      lesions.

PMID- 7735050
TI  - Helicobacter pylori: the Portuguese scene. Grupo de Estudo Portugues do
      Helicobacter pylori (GEPHP).

PMID- 7735048
TI  - Gastric epithelial cell proliferation.

PMID- 7735051
TI  - The prevalence of Helicobacter pylori infection in patients with intestinal
      metaplasia and in controls: a serological and histological study in four United
      Kingdom centres. The UK sub-group, the ECP-EURONUT Intestinal Metaplasia Study
      Group.

PMID- 7735052
TI  - The frequency of Helicobacter pylori associated peptic ulcer disease and of
      autoimmune-associated conditions in gastric and renal cancer: a retrospective
      comparison in 267 patients.

PMID- 7735053
TI  - The ECP-EURONUT intestinal metaplasia study--lifestyle and dietary data.

PMID- 7735054
TI  - ECP-EURONUT intestinal metaplasia study: gastric juice and urine analyses.

PMID- 7735055
TI  - The role of anti-oxidants in the chemoprevention of gastric cancer.

PMID- 7735056
TI  - The ECP-IM intervention study.

PMID- 7735058
TI  - Plague.

PMID- 7735057
TI  - Sustaining elimination of iodine deficiency disorders.

PMID- 7735059
TI  - Professional freedom of government leprosy personnel.
AB  - BACKGROUND: Government employment in India is known for its lack of flexibility.
      We studied whether this also involved professional freedom among health personnel
      working for the National Leprosy Eradication Programme. METHODS: The sample
      population consisted of National Leprosy Eradication Programme employees from
      Tamil Nadu and Andhra Pradesh and 8 health professional groups. A questionnaire
      was developed for each of them to elicit information on 5 aspects of their
      autonomy. They were studied individually and as homogeneous groups so that
      comparisons were possible both within and between groups in different regions who
      were conducting similar health programmes. RESULTS: National Leprosy Eradication
      Programme personnel enjoy a high degree of autonomy within the organization. This
      autonomy was evident in both states investigated, despite different
      administrations and it was not connected with the professional positions they
      held. Professional freedom correlated with the training activities, promotional
      prospects and commitment to the organization. CONCLUSIONS: The National Leprosy
      Eradication Programme job is not rigid because the organization is small and the
      intellectual needs of the professionals are met within it.

PMID- 7735060
TI  - Role of Helicobacter pylori in gastric carcinoma.
AB  - BACKGROUND: Helicobacter pylori infection has recently been incriminated in the
      pathogenesis of gastric carcinoma and chronic atrophic gastritis and intestinal
      metaplasia are considered to be precursors of this condition. Although the
      incidence of Helicobacter pylori infection in India is high that of gastric
      carcinoma is low. We, therefore, decided to examine the association between
      Helicobacter pylori, intestinal metaplasia and gastric carcinoma in a prospective
      study. METHODS: Fifty patients with carcinoma of the stomach and 50 with non
      ulcer dyspepsia underwent upper gastro-intestinal endoscopy and had biopsies from
      the antrum, body and carcinomatous tissue. In 12 cases of gastric carcinoma,
      tissue was obtained from resected specimens at operation. The types of gastritis,
      intestinal metaplasia and presence of Helicobacter pylori were assessed by
      staining with haematoxylin and eosin, periodic acid-Schiff reagent with alcian
      blue and Warthin-Starry stains. RESULTS: The incidence of chronic atrophic
      gastritis, intestinal metaplasia and Helicobacter pylori were 82%, 36% and 38% in
      patients with carcinoma and 86%, 4% and 68% in those with non-ulcer dyspepsia.
      Helicobacter pylori positivity was significantly higher (p < 0.05) and intestinal
      metaplasia significantly lower (p < 0.001) in patients with non-ulcer dyspepsia
      than in those with carcinoma. Of the 50 cases with carcinoma, 28 were of the
      intestinal and 22 of the diffuse type. The incidence of chronic atrophic
      gastritis, intestinal metaplasia and Helicobacter pylori in the intestinal type
      of carcinoma was 71%, 46% and 39% while in the diffuse type it was 32%, 23% and
      36%. The incidence of Helicobacter pylori infection did not differ significantly
      in the two types of carcinoma. CONCLUSIONS: We have found that although
      Helicobacter pylori infection and chronic atrophic gastritis are common in
      Indians, the incidence of intestinal metaplasia is low. Helicobacter pylori
      infection was equally common in both the intestinal and diffuse type of gastric
      carcinomas. Our findings, therefore, cast doubt on the role of Helicobacter
      pylori infection in gastric carcinogenesis.

PMID- 7735061
TI  - Antithrombin III levels in pregnancy induced hypertension.
AB  - BACKGROUND: Antithrombin III deficiency is common as well as severe in both
      consumptive coagulopathy and conditions such as pregnancy induced hypertension.
      We determined antithrombin III levels in women suffering from pregnancy induced
      hypertension to determine its usefulness in assessing severity of the disease and
      outcome. METHODS: Forty-five pregnant women with mild and severe forms of
      pregnancy induced hypertension and 18 women with normal pregnancies matched for
      gestational age formed the study population. Fasting blood samples were collected
      and the plasma separated. Antithrombin III levels were estimated by the kinetic
      Berichrom antithrombin III method. RESULTS: The mean (SD) antithrombin III levels
      [0.76 (0.233) IU/ml] were significantly lower in pregnancy induced hypertension
      compared to the control group [0.97 (0.234) IU/ml]. Low antithrombin III and high
      diastolic blood pressure (> 110 mmHg) were related to poor pregnancy outcome in
      primigravidae. CONCLUSION: Mean antithrombin III levels were lower in pregnancy
      induced hypertension compared to a control group of women especially those who
      were primigravidae and had a diastolic blood pressure > 110 mmHg. Since low
      antithrombin III levels and a high diastolic blood pressure result in adverse
      pregnancy outcome monitoring of antithrombin III levels in pregnancy induced
      hypertension may help in assessing foetal jeopardy.

PMID- 7735062
TI  - Transcervical endometrial resection when hysterectomy is dangerous.
AB  - Severe blood loss from dysfunctional uterine bleeding may be refractory to
      medical therapy and hysterectomy the only option. In two young women with severe
      bleeding where medical measures were ineffective and hysterectomy was a hazardous
      option, we performed a transcervical endometrial resection. In both of them the
      bleeding stopped immediately and no further treatment was required for
      dysfunctional uterine bleeding. They have had amenorrhea now for over six months.
      Transcervical endometrial resection is an option when hysterectomy is hazardous
      and the bleeding is refractory to medical treatment.

PMID- 7735063
TI  - Cell death by apoptosis and cancer chemotherapy.
AB  - The ways by which cell death takes place have generated great interest in recent
      years particularly in the field of cancer. The exact mechanisms which are
      responsible for tumour regression by drug treatment are also largely unknown and
      involve both enhanced cell death and arrested cell proliferation. Cell death is
      caused either by necrosis or by an active process in response to a specific
      stimulus which leads to elimination of a definite proportion of cells. This
      process of programmed cell death is referred to as apoptosis (a term coined by
      developmental biologists) and is a part of the morphogenetic processes,
      characterized by shrinkage of cells, condensation of nuclear chromatin, nuclear
      fragmentation and blebbing. Many successful cancer treatments presently
      undertaken depend upon induction of an apoptotic response in the target tumour
      cells. As apoptosis is considered to be an active gene-directed process, in
      tumours the precise mode of cell death after chemotherapy is important.
      Understanding the role of apoptosis in cancer will greatly broaden our knowledge
      of all stages of the disease process and its treatment. Thus, the role of
      apoptotic response modulation during the generation of neoplasia is an important
      issue and will remain an active area of present day investigations for improving
      the efficiency of chemotherapy. It is likely to become a valuable weapon in the
      war against cancer.

PMID- 7735064
TI  - Psychological deficits with long-term benzodiazepine use.

PMID- 7735065
TI  - Predicting insulin dependent diabetes mellitus.

PMID- 7735066
TI  - TNF-alpha alleles and susceptibility to cerebral malaria.

PMID- 7735067
TI  - Principles of drug therapy in heart failure.

PMID- 7735068
TI  - The medical profession: a sociological perspective.

PMID- 7735069
TI  - Advertising in medicine.

PMID- 7735071
TI  - Too many doctors! Not enough resources!

PMID- 7735070
TI  - Dietary trends in emerging city Africans: is urging a 'prudent' lifestyle a non
      starter?

PMID- 7735072
TI  - Scientific data on HIV transmission.

PMID- 7735073
TI  - Ciprofloxacin resistance among multidrug resistant strains of Salmonella
      senftenberg in India.

PMID- 7735074
TI  - The TRIPS agreement and pharmaceuticals.

PMID- 7735075
TI  - Anaemia in AIIMS outpatients.

PMID- 7735076
TI  - A "three-legged stool" for financing long-term care. Is it an acceptable
      approach?
AB  - To overcome the difficulty of seeking new funds for long-term care when public
      and private resources are severely constrained, a program entitled "Social
      Security/Long-Term Care" is proposed under which 5% of Social Security cash
      benefits can be traded (with exemption for low-income people) for a basic level
      of long-term care protection using social insurance. This program could be
      supplemented by private long-term care insurance, with Medicaid as a safety net.
      Financing thus generated may be used for home care, community-based care, and
      nursing home care. In 1994, 1% of Social Security cash benefits is equal to about
      $3.2 billion. Funds from Social Security/Long-Term Care could be used to help pay
      for a benefit package that could include case management.

PMID- 7735077
TI  - Case management in the acute care setting. A model for health care reform.
AB  - Case management, as a model for delivering health care, has a long history. Since
      its inception, the scope and goals of case management have changed and matured.
      Contemporary approaches to case management represent a dynamic, integrated, and
      multidisciplinary model of health care delivery. Case management incorporates
      interdependent and collaborative arrangements between the client and health care
      provider to ensure cost-effective, quality care. Because of its foundation in
      cost and quality control, case management is likely to be the delivery model that
      will play a major role in health care reform over the next decade, both in the
      acute care setting and in community-based, long-term care programs.

PMID- 7735078
TI  - A lifetime case management model for persons with spinal cord injury.
AB  - The development and implementation of case management within rehabilitation care
      settings are a major priority and strategic initiative for the 1990s. Within this
      setting, the special needs of an individual with spinal cord injury, managed
      within a comprehensive system of care, provide a framework for a case management
      construct. These needs extend over the individual's lifetime from the onset of
      the injury. Lifetime case management by expert rehabilitation practitioners
      addresses, anticipates, and manages the outcome and variances of care delivery
      and the individual response to a comprehensive system of care. This article
      describes the system of lifetime case management, the continuum of special care
      needs, and the role of the nurse clinician as an expert practitioner and lifetime
      case manager.

PMID- 7735079
TI  - Case management in a changing world.

PMID- 7735080
TI  - The quest for uniform guidelines for long-term care case management.
AB  - This article presents proceedings and preliminary findings from the National
      Advisory Committee on Long-Term Care Case Management, a group of nationally
      recognized case management experts from academia, provider organizations, and
      state and federal governments. The National Advisory Committee, supported by a
      grant from The Robert Wood Johnson Foundation, was created to achieve consensus
      about case management and explore the feasibility of developing case management
      practice guidelines for long-term care. Preliminary findings include endorsement
      of the need for guidelines, identification of core and ancillary functions of
      case management, and agreement to limit the scope of guidelines to the long-term
      care populations of frail elders and adults with chronic functional limitations.
      Final results and recommendations from the National Advisory Committee will be
      disseminated to government officials, policymakers, administrators, academicians,
      geriatricians, care providers, and long-term care community-based case managers.

PMID- 7735081
TI  - A generalist physician-based model for a rural geriatric collaborative practice.
AB  - This article describes a geriatric collaborative practice model in which primary
      care physicians (family practice and internal medicine) and nurse case managers
      are key members of a multidisciplinary team providing care to elderly rural
      patients in east central Illinois. Client characteristics, nursing case
      management roles, and the strengths and benefits associated with this geriatric
      collaborative model are presented.

PMID- 7735082
TI  - Case management and substance abuse: some observations and reflections.

PMID- 7735083
TI  - Practical issues in the application of case management to substance abuse
      treatment.
AB  - Interest in case management has grown in the substance abuse treatment field
      because of changes in the way we think about substance abuse, problems in the
      current delivery of treatment, subgroups of people have been identified who are
      unresponsive to currently available treatments or for whom special access
      problems are apparent. Case management is appealing because it involves accessing
      services and coordinating the care of individuals over long periods of time. This
      article briefly reviews the conduct of case management in substance abuse
      treatment by defining case management and discussing prevalent models, and then
      examining practical challenges faced in the implementation of case management.

PMID- 7735084
TI  - Strengths-based case management. A role in addressing denial in substance abuse
      treatment.
AB  - A strengths-based approach to case management is being used as an intervention to
      assist persons with substance abuse problems to access needed resources. The same
      strengths-based practice activities that support resource acquisition are also
      effective in addressing the denial that can interfere with substance abuse
      treatment. Both benefits, resource acquisition and a constructive approach to
      denial, have shown promise for enhancing client participation in treatment and
      subsequent outcome from that treatment.

PMID- 7735085
TI  - Appropriateness of assertive case management for drug-involved prison releasees.
AB  - Assertive case management models have been used successfully in both social work
      and mental health settings and, most recently, in the substance abuse field. This
      article reports on the application of an assertive case management model with
      drug-involved parolees in Delaware. Because of a variety of factors, the
      evaluation proved to be less than an ideal test of the effectiveness of the case
      management approach. Although there were some modest effects on reducing relapse
      to drug use, it appears that assertive case management is of limited value for
      clients who are not merely unable to access services, but who are often quite
      assertive in their unwillingness to make use of these services.

PMID- 7735086
TI  - Case management applications in substance use disorders.
AB  - Recent interest in the use of case management in services for people with alcohol
      and other drug dependence has arisen out of the successes and failures of the
      alcohol and drug treatment movement. Specifically, the realization that there are
      people with alcohol and other drug dependence who do not respond to current
      treatments has prompted a search for better ways to address complex problems.
      Case management is appealing in part because it is flexible, and can be adapted
      to fit many different populations, problems, and settings. It is particularly
      useful when recipients of services demonstrate unusually complex or intransigent
      problems, or their problems persist over long periods of time.

PMID- 7735087
TI  - Case management and community-based treatment of women with substance abuse
      problems.
AB  - Although there has been increased sensitivity to the needs and issues that face
      women with substance abuse problems, this continues to be an understudied and
      underserved population. To effectively address the needs of women, special
      efforts must be made to attract women into treatment settings and retain them.
      Furthermore, treatment programs must address the unique needs of women and
      provide a holistic range of services to adequately serve them. This article
      argues that strengths-based case management, provided in unison with
      comprehensive community-based programs, shows promise as an effective strategy to
      address the needs of women in alcohol and drug treatment.

PMID- 7735088
TI  - Case management to enhance HIV risk reduction among users of injection drugs and
      crack cocaine.
AB  - Case management is being applied to increasingly diverse client populations. This
      article describes the application of a field-based, service-broker model of case
      management with a population of injection drug users and crack cocaine users
      within the context of an AIDS risk-reduction program. The major problem
      encountered involved client engagement. The feasibility of implementing an
      effective case management program with active users of injection drugs and crack
      is questionable so long as involvement with such drugs is cast primarily as a
      criminal justice problem.

PMID- 7735089
TI  - Case management within a methadone maintenance program. A research demonstration
      project for HIV risk reduction.
AB  - The Los Angeles Enhanced Methadone Maintenance Project has incorporated case
      management in order to evaluate its effectiveness in reducing the risk of
      infection and/or transmission of human immunodeficiency virus among high-risk
      heroin addicts. Those recruited into the National Institute on Drug Abuse-funded
      treatment/research demonstration project were randomly assigned to either an
      enhanced group that received case management services or to a control group
      receiving standard methadone maintenance services. To date, the project has
      identified several barriers to implementation on a wide scale, including the
      inordinate amount of time spent assisting patients to procure basic necessities;
      the unwillingness of patients to participate in certain support services; and the
      reluctance of many service providers to work with methadone patients.

PMID- 7735090
TI  - Case management of substance abusers with HIV disease.
AB  - Case management is a promising intervention that has been used widely in many
      settings but is not well evaluated with substance abusers. This article describes
      a case management approach for substance abusers with human immunodeficiency
      virus (HIV) disease. Clients are enrolled from emergency and outpatient clinics
      of a general hospital. Case management focuses on encouraging a substance-free
      lifestyle, linking clients with needed services, and reducing their risk of
      transmitting HIV. A research project is currently underway to determine the
      effect of case management on client outcomes, assess its cost-effectiveness, and
      identify predictors of treatment participation and retention. Innovative models,
      such as case management approaches, can link drug abuse treatment with health
      care. These approaches may reduce the costs of care and improve the health care
      delivery system.

PMID- 7735091
TI  - Case management for substance abusers. More issues than answers.
AB  - Although case management has been successfully used in medical settings, its use
      for the delivery of multiple services for the substance abuser is questioned. An
      overview of the research suggests that low client-to-worker ratios, frequent and
      intense contacts, and chronic client relapse often contradict the emphasis on
      cost-containment, cost-effectiveness, and "successful" outcomes. The
      implementation of case management programs for substance abusers should proceed
      with caution. More emphasis should be placed on a community systems advocacy
      approach.

PMID- 7735092
TI  - [Hypoalgesia induced by weak stressor exposure, is accompanied by a decrease in
      antibody formation and change in the types of opioid receptors on immunocompetent
      cells].

PMID- 7735093
TI  - [Repeated induction of long-term potentiation after its saturation in rat
      hippocampal slices].

PMID- 7735094
TI  - [Replacement of a complex stimulus by one of its components in animal learning].

PMID- 7735095
TI  - [Correlation between morphologic and electrophysiological characteristics in
      neocortical transplants, located in the visual cortex of adult rats].

PMID- 7735096
TI  - [The spectrum of mutational damage to the phenylalanine hydroxylase gene in
      patients with phenylketonuria in St. Petersburg].

PMID- 7735097
TI  - [Conditioned media facilitates synchronization of oscillations in protein
      synthesis intensity in hepatocytes in vitro].

PMID- 7735098
TI  - [The effect of 4-substituted 1-N-methyl-tetrahydropyridines on binding of [3H]
      muscimol with rat brain synaptic membrane fractions].

PMID- 7735099
TI  - [Dual-photon absorption of visible light by proteins].

PMID- 7735100
TI  - [Synthesis of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate in a recombinant
      Escherichia coli culture].

PMID- 7735101
TI  - [The effect of medicinal leeches on the rheological properties of rat blood under
      normal conditions and upon development of experimental lipoidosis].

PMID- 7735102
TI  - [Neuronal plasticity of the enteral part of the metasympathetic nervous system in
      early postnatal ontogenesis].

PMID- 7735103
TI  - [Functional changes in the adrenal gland structure in response to removal of a
      specific midventral gland in the Campbell hamster].

PMID- 7735104
TI  - [Zearalenone as dopamine-beta-monooxygenase activator].

PMID- 7735105
TI  - [Determination of the timing of the beginning of differentiation of tyrosine
      hydroxylase-immunopositive neurons of the arcuate nucleus in male rats].

PMID- 7735107
TI  - [Localization of a family of MEL alpha-galactosidase genes on yeast left and
      right telomeres].

PMID- 7735106
TI  - [Genetic properties of alleles from genes on the X-chromosome isolated from
      natural Drosophila melanogaster populations during mutational bursts].

PMID- 7735108
TI  - [Interspecies effect of the boar sex pheromone: effect on the status of the
      female cattle sex cycle].

PMID- 7735109
TI  - [The mycotoxin zearalenone as an initiator of free radical lipid peroxidation in
      mitochondrial and microsomal fractions of white rat liver].

PMID- 7735110
TI  - [Ultrastructure of intrafusal motor endings in rat muscle spindle].

PMID- 7735111
TI  - [Participation of low threshold tactile skin afferents in reception of
      mechanically damaging factors].

PMID- 7735112
TI  - [Unusually prolonged extrachromosomal stability of plasmids containing fragments
      of retrotransposon MDG4, after transfection of Drosophila hydei cell cultures].

PMID- 7735113
TI  - [Morphometric analysis of dynamics of growth of cellular associates].

PMID- 7735114
TI  - [Substances, specifically disrupting organization of microtubules, block
      morphogenesis of epithelial structures].

PMID- 7735116
TI  - Replication sites as revealed by double label immunofluorescence against
      proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) in
      synchronized CHO cells and vincristine-induced multinucleate cells.
AB  - Double label immunofluorescence against PCNA and BrdU clearly revealed several
      characteristics of DNA replication sites in synchronized CHO cells. We observed
      that the distribution of replication sites changed from early to late S phase,
      particularly in the nucleolar and perinuclear regions, and the amount of PCNA in
      each replication site markedly decreased or disappeared with the progression of S
      phase. Although co-localization of PCNA and BrdU was usually seen, the intensity
      of fluorescence occasionally differed between the labeled PCNA and BrdU,
      particularly in late S phase. Based on the assumption that such a difference may
      reflect a different configuration of the chromatin, we propose that the brightly
      granular fluorescent staining of PCNA or BrdU in early S phase indicates a
      condensed segment of euchromatin. In the late S phase nucleus, we clearly
      observed a chromatin-like structure in the late replicating segments of
      heterochromatin in anti-PCNA stained material. In vincristine-induced
      multinucleate cells, a discrepancy between PCNA-distribution and BrdU
      incorporation in sister nuclei was sometimes seen. Such observations indirectly
      support the following two mechanisms for premature chromosome condensation
      proposed by others: asynchronous initiation of DNA synthesis; and a difference in
      the rate of DNA synthesis. In addition, the finding that BrdU was not
      incorporated into sites that had PCNA deposits suggests a third mechanism: the
      local disturbance of replication sites. Furthermore, unusual distribution
      patterns for replication sites suggest that the nucleation process in
      multinucleate cells differs from that in normal cells.

PMID- 7735115
TI  - Microinjection of Cdc25 protein phosphatase into Xenopus prophase oocyte
      activates MPF and arrests meiosis at metaphase I.
AB  - Microinjection of bacterially expressed human cdc25A protein into Xenopus
      prophase oocytes provokes the activation of p34cdc2 kinase and the tyrosine
      dephosphorylation of p34cdc2 in the presence or absence of protein synthesis. The
      level of p34cdc2 kinase activity then drops in parallel with the degradation of
      cyclin B2 and finally increases again to stabilize at a high level. Cdc25
      microinjection induces the assembly of a metaphase I spindle which is abnormally
      located in the deep cytoplasm. Moreover, oocytes arrest at the metaphase I stage
      and do not reach metaphase II even 10 h after cdc25 microinjection. The extended
      metaphase I period observed in cdc25-injected oocytes results from an equilibrium
      between degradation of cyclins and synthesis of new cyclins. This is in contrast
      with progesterone-stimulated oocytes where cyclin degradation is turned off when
      oocytes enter metaphase II. During metaphase I, the reactivation of MPF activity
      can be disrupted in two different ways: 1) cycloheximide, an inhibitor of protein
      synthesis, by preventing the synthesis of new cyclins, provokes the disappearance
      of MPF kinase activity and the reformation of a nucleus; 2) when the cAMP level
      is increased during the metaphase I period in cdc25-injected oocytes, MPF kinase
      activity drops following a rephosphorylation of tyrosine 15 of p34cdc2, while the
      cyclin turn-over remains unaffected. Moreover, increasing the cAMP level in
      prophase oocytes totally prevents the action of cdc25. Our results indicate that
      in Xenopus oocytes, the PKA pathway negatively regulates the activation of MPF
      and the activity of p34cdc2/cyclin B complex through tyrosine phosphorylation of
      p34cdc2 during metaphase I.

PMID- 7735117
TI  - Sister chromatid differentiation after in situ detection of ultraviolet-induced
      DNA breaks under electron microscopy.
AB  - Chinese hamster DON cells with 5-bromodeoxyuridine (BrdU)-substituted chromosomes
      were ultraviolet (UV)-exposed and processed for in situ detection of induced DNA
      breaks under electron microscopy. For this purpose, UV-induced breaks were
      amplified by an exonuclease III digestion to obtain single stranded DNA motifs
      which could hybridize with oligonucleotides of random sequences. These reannealed
      motifs could be used as primers which were extended by the Klenow polymerase,
      incorporating biotinylated-dUTP that was detected by a gold-tagged streptavidin.
      After processing, the chromatid whose DNA was BrdU-substituted in one strand
      showed a higher electron density than the chromatid substituted in both strands.
      In contrast, the unifilarly substituted chromatid showed about twice the
      labelling of DNA breaks as the bifilarly substituted one. This result could be
      the consequence of a greater loss of chromatin tracts in the bifilarly
      substituted chromatid, as implied by an X-ray microanalysis which showed that the
      amount of phosphorous lost by the bifilarly substituted chromatid was higher than
      that of the unifilarly substituted chromatid.

PMID- 7735118
TI  - Molecular and immunological characterization of a Trypanosoma cruzi protein
      homologous to mammalian elongation factor 1 gamma.
AB  - In previous studies, we reported the characterization of three Trypanosoma cruzi
      proteins with molecular masses of 45, 30 and 25 kDa eluted from a glutathione
      agarose column (these proteins were named TcGBP). Using antibodies against TcGBP
      native proteins we could isolate from a lambda ZAPII epimastigote cDNA library
      cDNA clones encoding the 30 and 25 kDa proteins. Comparison of the two sequences
      with amino acid sequences in several data banks revealed that both protein
      sequences were highly homologous to human and Artemia salina elongation factor 1
      beta. Thus, the proteins were named TcEF-1 beta 25 and TcEF-1 beta 30. In the
      present study we used a double immunoscreening strategy that allowed us to
      isolate a cDNA clone corresponding to the 45 kDa protein. The protein sequence
      revealed 31% identity and 61% homology with human and Artemia salina EF1 gamma
      and therefore was named TcEF-1 gamma. Moreover, three putative phosphorylation
      sites at position 51 (CSPC), at position 90 (RTPL) and at position 265 (PSPF)
      were found in the TcEF-1 gamma sequence. These sites are compatible with the
      notion that TcEF-1 gamma could be the target of phosphorylation by protein
      kinase(s). Random primed cDNA hybridized with a single 1.4 kb mRNA found in
      epimastigote, trypomastigote and amastigote forms. In addition, Southern blot
      analysis of genomic DNA suggested that the protein is encoded by a single gene.
      The TcEF-1 gamma cDNA was subcloned into the pGEX-4T-3 vector for expression in
      Escherichia coli.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735119
TI  - Uptake by rat liver of bovine growth hormone free or bound to a monoclonal
      antibody.
AB  - In the work reported here, we have compared the elimination from the blood, the
      uptake by the liver and the intracellular distribution of bovine growth hormone,
      free(Gh) or bound to a monoclonal antibody (GhAb). Results show that: a) the
      elimination from the blood is more rapid for Gh than for GhAb; b) both molecules
      are quickly taken up by the liver; c) probably after travelling through
      endosomes, Gh and GhAb get to lysosomes where they are degraded. However, Gh
      mostly ends in hepatocyte lysosomes while GhAb is recovered to a large extent in
      sinusoidal cell lysosomes; and d) binding by isolated hepatocytes is markedly
      less efficient for GhAb than for Gh.

PMID- 7735120
TI  - Effects of acidic pH on the formation of vinblastine-induced paracrystals in
      Chinese hamster ovary cells.
AB  - The pH-related change in morphology of vinblastine (VLB)-induced paracrystals
      formed in Chinese hamster ovary (CHO) cells was examined immunohistochemically in
      order to determine both the mechanism of tubulin crystallization and the
      influence of acidic pHs on cytoskeletal microtubules. Lowering the extracellular
      pH (pHe) rapidly reduced the intracellular pH (pHi) in CHO cells. Lowering the
      pHi to near the neutral range significantly accelerated the growth of VLB-induced
      paracrystals, compared to that of paracrystals formed at a physiological pHe.
      However, further cytoplasmic acidification caused by the addition of sodium azide
      into the culture medium induced the disappearance of typical paracrystals and the
      appearance of a highly organized meshwork of tubulin appearing as short, thick
      filaments at the light microscopic level. Treatments using different
      concentrations of VLB at different pHe's showed that low pHi's (6.7 and 6.3)
      suppressed paracrystal-formation at lower concentrations of VLB (5 x 10(-6) M and
      10(-5) M). At higher concentrations of VLB (5 x 10(-5) M and 10(-4) M), only
      short filaments were formed at pHi 6.3. Electron microscopy revealed that the
      filaments had a ladder-like structure probably consisting of a stacked series of
      fused rings. This indicates that paracrystals may be modified by extremely low
      pH. These results show that paracrystals are unstable in living cells and that
      their formation is regulated by environmental pH.

PMID- 7735121
TI  - The unique fibrillar arrangement of the bullfrog pressure-bearing tendon as an
      indicative of great functional deformability.
AB  - The fiber distribution and ultrastructure in the plantaris longus pressure
      bearing tendon of the bullfrog were investigated. The tension region of the
      tendon showed a predominant parallel distribution of collagen fibers, but three
      main zones with different crimp parameters were identified with the use of the
      polarizing microscope. The compression region showed collagen fibers with aspects
      of disaggregation and were composed of disperse and undulating fibrils. These
      collagen fibers establish a three-dimensional network but showed a preferential
      distribution in planes disposed perpendicularly to the tendon's main axis. It is
      assumed that the convoluted and disaggregated collagen fibers must be distended
      before exerting any reinforcement on the tissue and that this only occurs after a
      great deformation of the tendon. Groups of 5-6 fibrils not associated in fibers
      are also dispersed in the compression region. The tissue is assumed to have a
      highly viscous fluid nature allowing for the deformation needed for collagen
      fibrils to reinforce the tendon structure. The convoluted and crimped structure
      of collagen fibers would be especially useful when the tendon is submitted to the
      sudden and strong mechanical loading expected to occur during jumping and to
      provide the tendon with the capacity of great functional deformability necessary
      for the high amplitude of feet movements attained on jumping and swimming.

PMID- 7735122
TI  - Detection of quinoproteins after electrophoresis in the presence of urea or SDS.
AB  - A method for the direct detection of quinoproteins in gels after electrophoresis
      in the presence of urea or SDS has been developed. The conditions of sample
      preparation and detection were optimized to achieve maximum sensitivity. The
      method is suitable for the detection of quinoproteins in complex protein mixtures
      as well as for the characterization of certain enzyme preparations.

PMID- 7735123
TI  - The influence of cations and ionic strength on actin polymerization in the
      presence/absence of alpha-actinin.
AB  - The presence of alpha-actinin has little influence on polymerizing actin with
      regards to the lag phase, rate and amplitude. Rising KCl or MgCl2 concentrations
      parallel an increase in polymerization rate and a decrease in lag phase for both
      protein species. The observed overall smaller actin fluorescence amplitudes in
      the presence of alpha-actinin is due to a higher ratio of free G-actin to F-actin
      at steady state.

PMID- 7735124
TI  - Echistatin inhibits the adhesion of murine melanoma cells to extracellular matrix
      components.
AB  - Echistatin, an RGD containing peptide isolated from Echis carinatus snake venom,
      inhibited the in vitro attachment of B16-BL6 mouse melanoma cells to fibronectin,
      vitronectin and laminin. Its inhibitory activity on cell adhesion was non
      cytotoxic, dose-dependent and fully reversible. Kinetic analysis showed a
      competitive type of inhibition for all the three substrates examined here.
      Chemical reduction and alkylation of echistatin almost abolished its effect on
      cell adhesion to extracellular matrix components. Native echistatin was also able
      to inhibit B16-BL6 cell attachment to IgG antihuman fibronectin receptor-coated
      wells, thus suggesting that the molecule binds to adhesive receptors on melanoma
      cell surface. Our results indicate that echistatin is an useful disintegrin for
      research on cell adhesion.

PMID- 7735125
TI  - Quantitative determination of dihydroxyethylthiamine pyrophosphate by the
      circular dichroism method.
AB  - This work is concerned with a convenient and fast method for quantitative
      determination of dihydroxyethylthiamine pyrophosphate in solution where it is
      present as the only component or as a mixture with thiamine pyrophosphate (or
      other optically inactive compounds). The molar coefficient is given for circular
      dichroism absorption of dihydroxyethylthiamine pyrophosphate. The method for
      determining thiamine pyrophosphate in the presence of dihydroxyethylthiamine
      pyrophosphate is described as well.

PMID- 7735126
TI  - New roles of low density lipoproteins and vitamin E in the pathogenesis of
      atherosclerosis.
AB  - Accumulation of oxidized low density lipoproteins in macrophages and smooth
      muscle cells causes foam cell formation, an initial step in atherosclerosis.
      Active oxygen species are considered important in the pathogenesis of the
      disease. Antioxidants, such as tocopherols and tocotrienols have been considered
      to prevent the deleterious effects of active oxygen species. We found native low
      density lipoproteins can stimulate directly smooth muscle cell proliferation, it
      is associated with an increase of protein kinase C activity. d-alpha-Tocopherol,
      biologically most active form of vitamin E, inhibits both cell proliferation and
      protein kinase C activity. The effect of d-alpha-tocopherol is not related to its
      radical scavenging properties. Transforming growth factor-beta secreted by smooth
      muscle cells as growth inhibitor. Low density lipoproteins decrease the release
      of transforming growth factor-beta from smooth muscle cells thus activating
      growth. d-alpha-Tocopherol activates the cellular release of transforming growth
      factor-beta. These new aspects explain the important role of low density
      lipoproteins and vitamin E in increasing and decreasing the risk of
      atherosclerosis, respectively.

PMID- 7735127
TI  - Efficiency of Ginkgo biloba extract (EGb 761) in antioxidant protection against
      myocardial ischemia and reperfusion injury.
AB  - The cardio-protective mechanisms of EGb 761, an extract of Ginkgo biloba leaves,
      on myocardial ischemia-reperfusion injury were investigated using rabbits
      subjected to 30 minutes of regional cardiac ischemia and 120 min of reperfusion
      under anesthesia. Compared to the saline perfused group, EGb 761 treatment (10
      mg/kg, injected into the coronary artery) significantly inhibited the increase in
      lipid peroxidation and maintained total and CuZn-SOD levels in both plasma and
      tissue during and at the end of reperfusion. Both the decrease in tissue type
      plasminogen activator (t-PA) and the increase in plasminogen activator inhibitor
      1 (PAI-1) caused by ischemia-reperfusion were also significantly suppressed by
      EGb 761 treatment. Furthermore, the ultrastructure of the myocytes of the EGb 761
      treated heart was slightly damaged after ischemia-reperfusion, while the control
      ischemic-reperfused hearts demonstrated severe histological damages such as
      swelling and vacuolization of the mitochondria. These results suggest that EGb
      761 protects hearts by its antioxidant properties and by its ability to adjust
      fibrinolytic activity.

PMID- 7735129
TI  - Adrenaline stimulated glycogen breakdown in rat epitrochlearis muscles: fibre
      type specificity and relation to phosphorylase transformation.
AB  - The effect of adrenaline on glycogen breakdown in different skeletal muscle fibre
      types was investigated in the epitrochlearis muscle in vitro. Histochemical
      studies showed that adrenaline stimulated glycogen breakdown in all three major
      fibre types, with a higher absolute glycogen breakdown in type IIB fibres
      compared to type IIA and type I fibres. In biochemical studies we found that the
      glycogenolytic rate decreased during prolonged incubation with adrenaline,
      although the percentage phosphorylase in the a form and the concentration of
      glucose-6-phosphate (G-6-P) remained high. In the dose response studies we found
      an EC50 of 2.2 x 10(-8) M adrenaline for adrenaline stimulated glycogen
      breakdown, with an EC50 of 2.0 x 10(-7) M for adrenaline stimulated accumulation
      of G-6-P, excluding G-6-P as the key inhibitor of phosphorylase a activity.

PMID- 7735128
TI  - Cerebrin-50, a human cerebrospinal fluid protein whose mRNA is present in
      multiple tissues but predominantly expressed in the lymphoblastoid cells and the
      brain.
AB  - A full-length cDNA of 2295 bp coding for a human cerebrospinal fluid protein,
      designated cerebrin-50, has been isolated from a human brain cDNA expression
      library. Nucleotide sequence analysis of this cDNA revealed that it codes for a
      435 amino acid polypeptide which starts with an ATG initiation codon from the 5'
      end and ends with a TGA termination codon with a calculated molecular weight of
      51,484 daltons. A 10-amino acid peptide of NH2-SGDLETRYWG based on the deduced
      amino acid sequence of the cerebrin-50 cDNA was synthesized, conjugated to bovine
      serum albumin and was used to raise a monospecific polyclonal antibody in a
      rabbit. Immunoblot analysis using this antibody indicated the presence of a 52 kD
      protein in the human cerebrospinal fluid, brain cytosol, T lymphoblastoid cell
      conditioned medium, and human serum; it is also noted that the concentration of
      this 52 kD protein is several order of magnitude higher in the cerebrospinal
      fluid than in other biological fluids. The presence of its mRNA in the brain, T
      lymphoblastoid cells, spleen, liver, and testis was confirmed by sequential use
      of reverse-transcription and polymerase chain reaction (RT-PCR). Preliminary
      analysis by quantitative RT-PCR has noted that the expression of the cerebrin-50
      mRNA is higher in the lymphoblastoid cells and brain than the spleen, liver, and
      testis.

PMID- 7735130
TI  - Identification of two protein serine/threonine kinase genes and molecular cloning
      of a SNF1 type protein kinase gene from Toxoplasma gondii.
AB  - We report for the first time the identification of two protein kinase genes, in
      Toxoplasma gondii. Based on the conserved amino acid sequence motifs of catalytic
      subdomains VI(b) and IX of known protein serine/threonine kinases, degenerate
      oligonucleotides were synthesized and used in PCR to produce 196 and 373 bp DNAs.
      They encoded stretches of amino acid sequences characteristic of protein
      serine/threonine kinases. Dot and Southern blot analysis confirmed that these PCR
      products were of Toxoplasma origin. Screening of a genomic library of the
      organism with the 196 bp PCR product as a probe yielded 3 ToxPK1 g clones.
      Nucleotide sequence of two of these clones, revealed that the protein encoded,
      TOXPK1 resembled other carbon catabolite derepressing regulatory protein kinases.
      Therefore, we suggest that TOXPK1 could play a role in the interconversion of
      active and passive life-cycle stages of this parasite. RT-PCR studies on
      Toxoplasma tachyzoites' total RNA suggested that ToxPK1 gene is developmentally
      regulated. The 373 bp PCR product, however encoded a polypeptide that resembled
      the catalytic subunit of other cAMP-dependent protein kinases. Hence, this
      protein (TOXPK2) was considered as a product of another gene, ToxPK2.

PMID- 7735131
TI  - Cloning of HindIII digested bovine herpesvirus-1 DNA fragments from an Indian
      respiratory isolate.
AB  - The DNA from an Indian isolate of Bovine Herpesvirus-1 was isolated and analysed
      with restriction endonucleases. On shot gun cloning seven HindIII digested BHV-1
      DNA fragments could be cloned in pBR322 vector. Recombinant clones with viral DNA
      insert was identified by insertional inactivation of the selection marker and
      restriction analysis of recombinant plasmids with HindIII. Further, recombinant
      plasmids were analysed with HindIII, EcoRI and BamHI restriction endonucleases to
      identify the different viral DNA inserts. The restriction site map of recombinant
      plasmids were correlated with the map reported earlier. The southern blot of
      restriction digested recombinant plasmids was hybridized with radio-labelled BHV
      1 DNA as probe.

PMID- 7735132
TI  - Reactions of furfural and methylfurfural with DNA.
AB  - Furfural and methylfurfural are dietary mutagens and are present in various food
      products and beverages. The alkaline-induced unwinding of calf thymus DNA
      permitted the measurement of the number of strand breaks formed by furfural and
      methylfurfural, as a function of reaction time with these mutagenic agents. At
      the fixed DNA bp/mutagens molar ratio of 1:4, furfural treatment resulted in the
      formation of almost three times as many strand breaks at the end of 16 h
      reaction. In the presence of 0.2 M NaCl, a 60% reduction in strand breaks
      occurred in the case of furfural but only 25% with methylfurfural. It is also
      found that only in the case of methylfurfural treatment did depurination lead to
      the degradation of DNA, possibly through the alkylation of DNA bases and
      phosphates. These results suggest that furfural and methylfurfural may act on DNA
      by different reaction mechanisms.

PMID- 7735133
TI  - Alcohol metabolizing enzymes in the liver and stomach of the hamster.
AB  - It is established that the hamster prefers to drink alcohol under free choice
      situations. A gender difference in alcohol preference by the hamster has also
      been reported. In the present investigation, the alcohol metabolizing enzymes of
      hamsters of both sexes were measured. The liver alcohol dehydrogenase and
      aldehyde dehydrogenase activities were similar in both genders. A weak stomach
      alcohol dehydrogenase activity was also detected at high ethanol concentration;
      moreover, the activity of this enzyme in the male hamsters was 22% higher than
      that in the females. The total alcohol dehydrogenase activity in the stomach was
      less than 0.5% of that in the liver. Such a low activity suggested that the
      enzyme was unlikely to play a significant role in explaining the gender
      difference on alcohol preference in the hamster.

PMID- 7735134
TI  - Role of arginine residues of bovine liver dihydrodiol dehydrogenase 2 in the
      binding of anionic substrates.
AB  - Bovine liver dihydrodiol dehydrogenase (DD2) was inactivated following pseudo
      first order manner by the treatment of 5 mM 2,3-butanedione (BD) as functions of
      incubation-time and concentration. Anionic substrates or analog which have a
      carboxyl group, D-glucuronate, p-carboxybenzaldehyde and D-glycerate, protected
      DD2 efficiently. But, the other substrates or coenzymes and their analogs did not
      show any protection on the inactivation, i.e., D,L-glyceraldehyde, D-erythrose,
      NADP+, NAD+, 2',5'-ADP, 2'-AMP. Results of kinetic analyses suggest that the
      inactivated enzyme lost its binding ability to anionic substrates. The
      inactivated enzyme was reactivated very effectively by removing excess BD by
      gelfiltration for 30 min.

PMID- 7735135
TI  - Effect of DNA methylation on protein-DNA interactions upstream of the gamma
      glutamyl transpeptidase gene.
AB  - We have used exonuclease III and DNase I protection assays to study proteins
      which bind to potentially regulatory elements located in the 5'-flanking region
      of the gamma-glutamyl transpeptidase gene. With both liver and kidney nuclear
      extracts, exonuclease III barriers were located at -566 in the coding strand and
      at -585 in the noncoding strand, and footprints were found from -595 to -566 and
      from -600 to -562, respectively. When the DNA was methylated in the CG
      dinucleotides, the exonuclease III barriers disappeared and the footprints were
      greatly reduced. The transcription factor Sp1 bound to this DNA region but did
      not seem to be involved in the binding activity. Since the gamma-glutamyl
      transpeptidase presents different levels of methylation in liver and kidney,
      associated with different levels of expression, these results suggest that the
      binding activity could play a role in the control of the expression of the gamma
      glutamyl transpeptidase gene in liver and kidney.

PMID- 7735136
TI  - Expression of osteopontin messenger RNA in the rat kidney on experimental model
      of renal stone.
AB  - We investigated the expression of osteopontin (OPN) messenger (m) RNA in the rat
      kidney under the experimental models of several conditions that are considered to
      be risk factors of human renal stones. In the renal stone formation model
      administrated glyoxylic acid and 1,25-dihydroxyvitamin D3, pyelonephritis model
      and hydronephrosis model the expression of OPN mRNA in the distal convoluted
      tubule of the kidney was enhanced compared with the control which was
      sporadically positive utilizing in situ hybridization and northern blot analysis.
      The expression of OPN mRNA was markedly inhibited in the renal stone formation
      model by concominant administration of estradiol and/or progesterone.

PMID- 7735137
TI  - Cytochrome P-450scc-catalyzed production of progesterone from cholestenone.
AB  - Cholestenone, which is a 3-keto derivative of cholesterol, was incubated with
      cytochrome P-450SCC in a reconstituted hydroxylation system. Cholestenone was
      metabolized to progesterone with a turnover number of about 9 nmol/min/nmol P-450
      in the presence of 0.01% Tween20. This value was about 70% of the maximal value
      for cholesterol. The final reaction product, progesterone, and three other minor
      reaction products, 20 alpha-hydroxycholest-4-en-3-one, 22R-hydroxycholest-4-en-3
      one, 20,22-dihydroxycholest-4-en-3-one, were identified on the basis of its
      retention times on HPLC, thus suggesting them to be intermediates of side-chain
      cleavage of cholestenone. The results suggest that cholestenone is metabolized by
      two pathways, that is, the first hydroxylation occurs either at the C-20 position
      or at the C-22 position.

PMID- 7735138
TI  - Double-C-peptide human proinsulin.
AB  - A fusion gene encoding double-C-peptide human proinsulin was constructed by
      insertion of a DNA fragment encoding human C-peptide into the 5'-terminal C
      peptide coding sequence of a synthetic human proinsulin gene with correct reading
      frame and over-expressed in E. coli. The purified double-C-peptide human
      proinsulin shows decreased activity in receptor binding and insulin immune assays
      as compared with human proinsulin. Disulphide bond reconstitution studies
      demonstrate that there is not much more influence of the protein concentration on
      the yield of refolded double-C-peptide human proinsulin. The double-C-peptide
      human proinsulin shows a 1.86-fold human C-peptide immune activity as compared
      with that of human proinsulin and gives a good yield of the molecule with correct
      disulphide bonds in reconstitution studies strongly suggesting the existence of
      very flexible conformation of the C-peptide.

PMID- 7735139
TI  - Low density lipoprotein oxidation is inhibited by extracts of Ilex
      paraguariensis.
AB  - Some dietary polyphenolic substances have been shown to inhibit oxidation of LDL.
      "Mate" is a polyphenol-containing beverage, brewed from the dried and minced
      leaves of Ilex paraguariensis. In the present work we studied the effect of water
      and alcohol extracts of Ilex paraguariensis on the initiation and propagation of
      LDL copper or H2O2-induced autoxidation. Our data show that substances in water
      extracts of Ilex paraguariensis are capable of inhibiting the initiation and the
      propagation of LDL oxidation. They inhibit lipid peroxidation, monitored by diene
      conjugates and thiobarbituric acid-reactive substances, as well as protein
      modification as shown through direct measurement of free amino groups,
      electrophoretic mobility, and fluorescence. This inhibition is a concentration
      dependent effect that becomes already apparent at concentrations of extracts as
      low as 7.5 micrograms/ml. Inhibition is almost complete at 37.5 micrograms/ml.
      Alcohol extracts show similar effects though with less potency. The substances
      implicated in this antioxidant activity are largely nondializable. In terms of
      mass, water extracts of Ilex paraguariensis were more potent antioxidants than
      either ascorbic acid, or butylated hydroxytoluene.

PMID- 7735140
TI  - Genomic structure of c-Ki-ras proto-oncogene of the hermaphroditic fish Rivulus
      marmoratus (teleostei: Rivulidae).
AB  - The ras homologue of the rivulid fish Rivulus marmoratus was isolated and
      characterized by screening about 3.0 x 10(5) genomic clones from a Rivulus
      genomic library using human c-Ha-ras probe. When this clone was partially
      sequenced focusing on the region coding exons, it showed 97.5% amino acid
      homology to the human c-Ki-ras gene. The Rivulus c-Ki-ras gene spans about 6.3 kb
      and consists of five exons including the alternative splicing exon 4a/4b. The
      exon-intron boundaries of Rivulus c-Ki-ras gene coincided with the GT/AG rule of
      consensus splice acceptor and donor sequences as in mammalian c-Ki-ras genes.
      Amino acid sequence analysis of some domain regions of the Rivulus c-Ki-ras gene
      revealed 100% identity to mammalian c-Ki-ras gene. This report is the first that
      elucidate the entire structure of c-Ki-ras in a fish.

PMID- 7735141
TI  - Effect of peroxisomes proliferators and hypolipemic agents on mitochondrial inner
      membrane linked D-3-hydroxybutyrate dehydrogenase (BDH).
AB  - 1. D-3-hydroxybutyrate dehydrogenase EC 1.1.1.30 (BDH) activity was measured in
      mitochondria of rats submitted to an intermittent feeding treatment with
      ciprofibrate or fenofibrate, i.e. fibrate analogues with hypolipemic activity and
      peroxisome proliferation properties. Our data shows an inhibition of rat liver
      mitochondrial BDH activity. This inhibitory effect is abolished when the
      treatment is stopped and reappears after a second treatment. 2. Incubation of
      hypolipemic agents (ciprofibrate, clofibrate, clobuzarit, fenofibrate or 2,4
      dichlorophenoxyacetic acid) with submitochondrial linked BDH leads to an
      inhibition in a concentration dependent manner. 3. The protection by NAD(H)
      (coenzymes) and by methyl-malonate (a substrate analogue and competitive
      inhibitor) indicates that the inhibition occurs in the active site. On the other
      hand, there is a strong protection by phospholipid vesicles. This trapping effect
      may be attributed to lipophilic properties of hypolipemic agents. 4. Comparative
      effect of hypolipemic agents on mitochondrial BDH activity from rat liver and
      from Tetrahymena pyriformis indicates the same inhibition and same protection
      effects. This supports conservation of the enzymatic properties according to the
      evolution.

PMID- 7735142
TI  - Effect of a p-nitro group of phenyl-maltooligosaccharide substrate on the change
      of action specificity of lysine-modified porcine pancreatic alpha-amylase.
AB  - The effect of chemical modification of lysine residues on the activity of porcine
      pancreatic alpha-amylase (PPA) was examined, using p-nitrophenyl-alpha-D
      maltoside, p-nitrophenyl-alpha-D-maltotrioside, phenyl-alpha-D-maltoside and
      phenyl-alpha-D-maltotrioside as substrates. Chemical modification of PPA with
      trinitrobenzenesulfonic acid enhanced the kcat/Km values for p-nitrophenyl
      substrates, but not for phenyl substrates. Thus, this effect is substituent
      selective. Considering the productive binding modes of substrates to PPA, the p
      nitro group of the substrate and the modified lysine residues of the enzyme would
      non-ionically interact with each other to stabilize the productive binding mode.

PMID- 7735143
TI  - Effect of sphingomyelin and antioxidants on the in vitro and in vivo DNA
      methylation.
AB  - Sphingomyelin and product of its enzymatic hydrolysis, sphingosine, influence on
      the degree of DNA methylation by EcoRII cytosine DNA-methyltransferase.
      Sphingomyelin activates (up to 30%), whereas sphingosine inhibits this in vitro
      DNA methylation. A single intraperitoneal injection of the synthetic antioxidant,
      butylated hydroxytoluene (BHT, 30 mg/kg body weight) results in DNA
      hypermethylation as well as increase in sphingomyelin content in rat liver nuclei
      and RNA-polymerase activity. Thus, phospholipids may control DNA methylation in
      cell, and by this way they seem to modulate replication and transcription.

PMID- 7735144
TI  - Spontaneous overexpression of heat-shock proteins in Ehrlich ascites carcinoma
      cells during in vivo growth.
AB  - Ehrlich carcinoma (EC) cells isolated from mice at different phases of ascites
      growth were exposed to hyperthermia (44 degrees C), or oxidative stress (hydrogen
      peroxide or vikasol), or ATP depletion induced by rotenone. These exposures
      caused protein aggregation and rapid necrotic death in exponentially growing EC
      cells. On the contrary, the same cell culture at stationary phase of growth
      became considerably more resistant to all the above cytotoxic treatments, and the
      level of aggregated protein was significantly lower in stressed stationary EC
      cells than that in exponential ones. Comparative immunoblotting has revealed the
      unexpected expression of inducible 70 kDa heat-shock protein form (HSP68), as
      well as accumulation of HSP27 and HSP90 in the thermo- and drug-resistant
      stationary EC cells. It is suggested that the in vivo occurring HSP
      overexpression in stationary EC cells is an adaptive modulation of the tumor cell
      phenotype to maintain the viability of ascites EC cells under chronic deficiency
      of oxygen and nutrients.

PMID- 7735145
TI  - Special double issue on otoacoustic emissions.

PMID- 7735146
TI  - Lateral and medial efferents: a double neurochemical mechanism to protect and
      regulate inner and outer hair cell function in the cochlea.
AB  - In the mammalian cochlea, the two types of hair cells drastically differ in their
      anatomy and physiology. Each system receives a specific efferent control
      originating in the brainstem superior olivary complex. Inner hair cells are
      connected to the afferent type I ganglion neurons (comprising 95% of the auditory
      nerve) which postsynaptically receive the input of the lateral efferents. On the
      other hand, outer hair cells, whose electromotile properties are responsible for
      the active mechanism, are directly under medial efferent control.
      Neurochemically, both types of efferents are also well distinguished. The present
      paper reviews the efferent neurochemistry and pharmacology, with an emphasis on
      the protective roles of each system on cochlear function. The role of lateral
      efferent neurotransmitters such as enkephalins and dopamine in protecting the
      auditory nerve dendrites against excessive noise and/or excitotoxicity is
      especially addressed. The cholinergic medial efferents synapsing with the outer
      hair cells play a role in altering and/or modulating cochlear micromechanics.
      They could also be involved in a potentiating effect on aminoglycoside
      ototoxicity.

PMID- 7735147
TI  - Ipsilateral suppression effects on transient evoked otoacoustic emission.
AB  - The spectral properties of click- and tone-evoked otoacoustic emission (OAE)
      under ipsilateral simultaneous tonal masking conditions as well as the changes of
      click-evoked OAE under ipsilateral forward masking by clicks were studied in
      normal-hearing subjects. It was found that (i) transiently evoked OAE (TEOAE)
      spectra consist of a number of peaks individual to the subject and distributed
      along a sufficiently wide cochlear region; (ii) each spectral peak is excited
      only when the stimulus energy was concentrated within the frequency range
      covering the frequency of the particular peak; (iii) different TEOAE spectral
      peaks can be masked independently under simultaneous tonal masking conditions;
      (iv) the TEOAE tuning curve shape is more closely related to the spectrum of
      TEOAE but not to that of the stimulus; (v) forward masking of TEOAE generation is
      most pronounced during the first few milliseconds after masker click onset and
      become significantly smaller with the longer latency. It is suggested that: (i)
      TEOAE is generated by a number of local generators individually distributed along
      the cochlear partition within a sufficiently wide region and characterized by
      different power; (ii) possible efferent effects in the ipsilateral TEOAE
      suppression are negligible as compared to the TEOAE reduction of exclusively
      cochlear origin.

PMID- 7735148
TI  - Suppression tuning characteristics of 2f1-f2 distortion product otoacoustic
      emissions.
AB  - The 2f1-f2 distortion product otoacoustic emission (DPOAE) is suppressed by a
      third tone following a frequency selective pattern and outlining tuning curves
      which are generally similar to neural and psychophysical findings. The most
      effective suppressor tone lies between f1 and f2; less suppressive effects are
      produced by an added tone that lies in the 2f1-f2 site. The slope of iso
      suppression curves is much steeper on the higher flank than on the lower flank of
      the suppression curve (respectively 100-115 dB/octave and 25-35 dB/octave). A
      suppression fine structure can be observed in the region of the tip especially
      for higher DPs probably connected with the fine structure of distortion products
      and with the instability of cochlear activity. A saturation point, around 70 dB
      or more has been evidenced on the growth rate functions. Continuous and
      interrupted suppressor presentation can induce some differences in the responses.
      Suppression of DPOAEs can provide a wider knowledge on active non-linear
      mechanisms in the cochlea, and on frequency selectivity also in a clinical
      context.

PMID- 7735149
TI  - Contralateral auditory stimulation and otoacoustic emissions: a review of basic
      data in humans.
AB  - The influence of contralateral auditory stimulation on otoacoustic emissions
      (OAE), spontaneous OAE, evoked OAE and acoustic distortion products, can be
      summarized as follows: (1) alteration (mainly a decrease) of OAE amplitude; (2)
      alteration of response spectrum (upward shift frequency of SOAE); (3) alteration
      of phase; (4) effect dependent on intensity of contralateral stimulation; (5)
      effect inversely dependent on intensity of ipsilateral stimulation; (6) frequency
      specificity of the suppressive effect. Involvement of the medial olivocochlear
      bundle is highly probable but one cannot exclude a double pathway including also
      the acoustic reflex.

PMID- 7735150
TI  - Contralateral suppression of TEOAE. Attempts to find a latency.
AB  - Latency of the contralateral suppression of transient-evoked otoacoustic
      emissions (TEOAE) has been investigated using the ILO88 system for ipsilateral
      stimulation and recording, and a laboratory computer interface producing
      contralateral noise bursts. Reduction of rms amplitude in the last 10.24 ms of
      the response was found to produce the most consistent indication of suppression.
      Onset latencies varied from less than 40 ms to 140 ms, offset latency from 20 ms
      to more than 80 ms. Acoustic reflex latencies have not been reported with such
      short latencies and this makes it unlikely that this reflex can be responsible
      for the contralateral suppression of TEOAE. This study used contralateral stimuli
      at 70 dB HL. Lower level stimuli may result in increased amplitude and it is also
      possible that the effect of contralateral stimulation may be frequency specific.
      The long offset latency necessitates long intervals between stimuli with an
      inherent risk of variation in stimulus and recording conditions. This makes an
      elaborate study of the latency difficult to perform in humans.

PMID- 7735151
TI  - Contralateral and ipsilateral 'suppression' of evoked otoacoustic emissions at
      high stimulation rates.
AB  - A previous study has shown that the amplitude of otoacoustic emissions decreases
      with increase in stimulus rate. Furthermore, these changes are similar to the
      changes initiated by contralateral suppression of the click-evoked otoacoustic
      emission. Further studies have been carried out which showed that contralateral
      suppression, due to a 60 dB SL white-noise suppressor, has a magnitude of about
      2.7 dB for the normal subjects used in this study. The equivalent ipsilateral
      'suppression' is approximately 8 dB at a stimulus rate of 2000 clicks/s. The two
      effects have an equivalent magnitude at a stimulus rate of approximately 300
      clicks/s. In acoustic neuroma patients, where the nerve pathway is impeded by the
      tumour, the ipsilateral 'suppression' effect is virtually absent. These findings
      suggest that an ipsilateral 'suppression' similar in form but larger in magnitude
      than the more usual contralateral suppression can be created by increasing the
      stimulus rate using maximum length sequence (MLS) techniques.

PMID- 7735152
TI  - Contralateral suppression of transient evoked otoacoustic emissions: intra
      individual variability in tinnitus and normal subjects.
AB  - Contralateral acoustic stimulation reduces the amplitude of the transient evoked
      otoacoustic emission (TEOAE) in humans. The mechanism is thought to be mediated,
      at least in part, through the medial olivocochlear efferent system innervating
      the outer hair cells. To assess its usefulness as a possible clinical test, TEOAE
      suppression was measured in each ear of 12 subjects over a 6-week period, and
      these data are shown in detail for four subjects representing extremes of
      variability in a tinnitus and a non-tinnitus group. Intra-subject test results (n
      = 18) exhibited a varying extent of suppression values and the variance of each
      session, consisting of three tests, was not statistically different from one
      session to another. There was no dependence on variables such as ear (right or
      left), session, day of testing or their interaction. There was a significant
      difference in the variability between the tinnitus and the normal group.

PMID- 7735153
TI  - Contralateral suppression of transiently evoked otoacoustic emissions and neuro
      otology.
AB  - Transiently evoked otoacoustic emissions can be suppressed with simultaneous
      contralateral sound stimulation. This is considered to be effected via the
      efferent pathway from the superior olivary complex (SOC) to the contralateral
      cochlea. This study examined this effect in patients with extrinsic and intrinsic
      lesions of the brainstem which may affect the efferent pathway either within the
      vestibular nerve which carries the efferent bundle to the cochlea or within the
      brainstem at the level of the SOC. Suppression is reduced or absent in these
      patients and the site and size of the lesion determines whether the suppression
      is affected unilaterally or bilaterally. Lesions affecting the auditory afferent
      pathway without significant alteration in hearing appear to affect the efferent
      pathway too.

PMID- 7735154
TI  - Contralateral suppression of transiently evoked otoacoustic emissions and
      tinnitus.
AB  - The present paper reports individual data obtained in three different patients
      who consulted for unilateral tinnitus in the Department of Otolaryngology. After
      pure tone and high-frequency audiometry, Audioscan audiometry was recorded, and
      tinnitus measurement which comprised a determination of pitch and loudness
      matches. Spontaneous, transient evoked and 2f1-f2 distortion product otoacoustic
      emissions at 65 dB SPL stimulus intensity were then determined. The functioning
      of the medial olivocochlear system (MOC) was also tested from a comparison
      between OAE input/output curves obtained in the presence and absence of 30 dB SL
      contralateral stimulation by a broadband noise: MOC global effectiveness was
      assessed through transient evoked emissions while those concerning distortion
      product emissions allowed a precise testing at the tinnitus frequency itself. The
      examples here displayed illustrate the diversity of results that can be found in
      such investigations, thereby preventing a general law to be established from the
      global testing of MOC functioning. On the contrary, the local testing at the
      precise frequency of tinnitus revealed the existence of an alteration of MOC
      functioning in at least one ear as shown by either a weak, null or inverse effect
      of contralateral stimulation. A better understanding of the sensorineural forms
      of tinnitus should come from the extensive investigation of MOC efficiency along
      the basilar membrane when routine clinical investigations lead one to suspect an
      involvement of this system, due to discordant damaging between inner and outer
      hair cells. Such studies would allow one to test the validity of hypotheses which
      invoke MOC-related mechanisms as an essential link for the emergence and
      persistence of tinnitus.

PMID- 7735155
TI  - Contralateral suppression of transient evoked otoacoustic emissions in guinea
      pigs: effects of gentamicin.
AB  - A single injection of gentamicin in the awake guinea-pig induces a transient
      blockade of the suppression by contralateral white noise of tone-pip evoked
      compound action potential (Smith et al., 1994). We report here the reversible
      blockade, in exactly the same experimental conditions, of the suppression of
      click-evoked otoacoustic emissions. These observations confirm the transient
      action of gentamicin at the medial efferent/outer hair cell synapse, likely via
      the reversible blockade of calcium channels observed in vitro (Dulon et al.,
      1989).

PMID- 7735156
TI  - Acoustic distortion products (ADP) from the ears of term infants and young adults
      using low stimulus levels.
AB  - It has been shown previously that relatively low stimulus levels (L1 = 55, L2 =
      40 dB SPL) elicit recordable levels of ADP from healthy adult ears (Gaskill and
      Brown, 1990). We have used the same stimulus levels in healthy term infants
      within 6 days of birth. The results from the 38 infants who provided data from
      both ears (from a total of 66 attempted) are reported here. The data were
      compared with those from 12 adults aged 20 to 30 years with normal audiometric
      thresholds. ADP was measured across frequency with f2 (the high frequency tone)
      between 1 and 8 kHz (infants) and 0.5 kHz and 8 kHz (adults) and f1 (the low
      frequency tone) determined by f2/1.225. ADP was also measured at a range of
      different stimulus frequency separations. The mean level of ADP was higher in
      infant than in adult ears but this difference was not significant. The f2/f1
      ratio of approximately 1.2 which has been widely adopted for use in adults is
      also an appropriate frequency separation for term infants.

PMID- 7735157
TI  - Temperature dependency of the frequency and level of a spontaneous otoacoustic
      emission during fever.
AB  - Using a method of heterodyne mixing with display of beats on a chart recorder,
      measurements were made of the frequency and level of a spontaneous otoacoustic
      emission in a human subject on 17 occasions during a period of 13 consecutive
      days. Temperature measurement was obtained with a thermometer measuring infra-red
      radiation from the ear-drum, indicative of body core temperature. In the latter
      half of this period there was variation of body set point temperature due to
      fever, and it was found that there was clear evidence of inverse relationship
      between temperature and both the frequency and level of the emission. The
      occurrence of fever was due to simple urinary tract infection and was considered
      to be without ototoxic implication; there was no associated worsening of pure
      tone threshold nor change in measurements of middle ear function.

PMID- 7735158
TI  - Uptake mechanisms of meta-[123I]iodobenzylguanidine in isolated rat heart.
AB  - In order to clarify the uptake and retention mechanisms of radioiodinated meta
      iodobenzylguanidine (MIBG) in heart, the kinetics of no-carrier-added [123I]MIBG
      were studied in the isolated working rat heart in interaction with pharmacologic
      agents. The tracer was administered in the perfusate as a 10-min pulse, followed
      by a 90-min washout period. Kinetic analysis of the externally monitored time
      activity curves of control hearts showed avid uptake (Ki = 4.4 +/- 0.7 mL/min/g),
      and monoexponential clearance (ko = 0.0056 +/- 0.0017 l/min), indicating a
      distribution volume (Vd = Ki/ko) of 834 +/- 214 mL/g. Blocking experiments (n =
      41) were performed with neuronal uptake (uptake-1) inhibitor desipramine (DMI; 50
      100 nM) and the extraneuronal uptake (uptake-2) inhibitor N-(9-fluorenyl)-N
      methyl-beta-chloroethylamine (SKF550; 0.4-0.8 microM). Uptake rate was 27%
      reduced (P < 0.05) by 50 nM DMI but not significantly affected by 0.4 microM
      SKF550. Distribution volume was 88% reduced (P < 0.0005) by 50 nM DMI and 28%
      reduced (P < 0.05) by 0.4 microM SKF550. In DMI-blocked hearts, uptake rate was
      dramatically decreased (-80%, P < 0.0005) by SKF550 (0.4 microM), indicating
      uptake-2 transport contributed predominantly to the extraneuronal uptake of the
      tracer. The slow uptake rate seen with concomitant inhibition of uptake-1 and
      uptake-2 was further decreased by addition of unlabeled MIBG (1-10 microM) in a
      concentration-dependent manner, yet unaffected by addition of the vesicular
      uptake inhibitor Ro 4-1284 (1 microM). Thus, the uptake rate of [123I]MIBG is
      primarily dependent on uptake-1 and uptake-2 activity. Other possible mechanisms
      of uptake such as passive diffusion in association with intracellular binding are
      significant only in conditions where uptake-1 and uptake-2 mechanisms are largely
      inhibited.

PMID- 7735159
TI  - Preparation of [11C]formaldehyde using a hollow fiber membrane bioreactor.
AB  - A bioreactor consisting of the enzymes alcohol oxidase and catalase immobilized
      onto a hollow fiber membrane was used to convert [11C]methanol to
      [11C]formaldehyde. Using an alcohol oxidase:catalase ratio of 1:500 U, conversion
      yields of 90-95% were obtained allowing the production of up to 7400 MBq (200
      mCi) of [11C]formaldehyde in 5 min. The hollow fiber bioreactor allowed for a
      convenient, rapid synthesis with yields significantly higher than the standard
      chemical procedures, has demonstrable advantages over glass bead immobilized
      systems (primarily due to convective flow), and was amenable to hot cell
      conditions.

PMID- 7735160
TI  - Electrophilic 18F from a Siemens 11 MeV proton-only cyclotron.
AB  - Because more and more PET centres are using small proton cyclotrons there is a
      renewed interest in methods for the production of electrophilic 18F by proton
      irradiation of [18O]O2. A method for the routine production of clinically useful
      quantities of [18F]F2 having a specific activity of 35 Ci/mmol has been developed
      and implemented using an 11 MeV proton cyclotron and [18O]O2. Based on the yield,
      purity, reproducibility, and specific activity of [18F]F2 this is the most
      efficient method reported thus far.

PMID- 7735161
TI  - Development of bone marrow immunoscintigraphy using a Tc-99m labeled anti-NCA-95
      monoclonal antibody.
AB  - We evaluated the monoclonal antibody CEA-79.4 against carcinoembryonic antigen as
      an immunoscintigraphic agent for assessing the state of the bone marrow. Western
      blotting of human granulocyte extracts with the antibody could confirm that the
      binding was with the epitope of NCA-95. Immunocytochemical staining of bone
      marrow aspirates revealed specific uptake of this antibody by granulopoietic
      cells. The affinity constant was 2-9 x 10(9) L/mol. Immunoscintigraphy using
      99mTc-labeled CEA-79.4 in a normal volunteer revealed high uptake in the bone
      marrow as compared to other organs.

PMID- 7735162
TI  - 76Br-labeled monoclonal anti-CEA antibodies for radioimmuno positron emission
      tomography.
AB  - For the application of anti-tumor monoclonal antibodies (MAbs) in positron
      emission tomography (PET), labeling radionuclides with half-lives allowing a
      suitable time frame for imaging are required. The anti-CEA MAb 38S1 was labeled
      with the positron emitting nuclide 76Br (t1/2 16 h) using bromoperoxidase (BPO),
      and subsequently affinity purified. A procedure was devised to allow reproducible
      production of MAb-preparations of high immunoreactivity and with acceptable
      bromination yield. The biological activity of 76Br-38S1 was retained and
      comparable to that of chloramine-T labeled 125I-38S1, as tested in vitro.

PMID- 7735163
TI  - Synthesis, in vivo biodistribution and dosimetry of [11C]N-methylpiperidyl
      benzilate ([11C]NMPB), a muscarinic acetylcholine receptor antagonist.
AB  - 4-N-Methylpiperidyl benzilate (NMPB), a high affinity antagonist for the
      muscarinic cholinergic receptor, has been synthesized in carbon-11-labeled form
      through the N-[11C]methylation of 4-piperidylbenzilate. The product was isolated
      by HPLC, and obtained in yields (> 100 mCi) and specific activities (500-3000
      Ci/mmol) sufficient for in vivo evaluation in small animals. Time-dependent
      regional brain distributions in rats and mice showed high radiotracer uptake and
      retention in striatum and cortex, and low in cerebellum, consistent with
      muscarinic cholinergic receptor distributions. Radiotracer retention in tissues
      could be significantly reduced by pretreatment of animals with a large dose of a
      competing antagonist, quiniclidinyl benzilate. Whole body biodistribution in rats
      was used to calculate the expected human internal radiation dosimetry for this
      new radiopharmaceutical. These animal experiments formed the basis for subsequent
      introduction of [11C]NMPB into human use with positron emission tomography.

PMID- 7735164
TI  - Differential hepatic response of 65Zn distribution between mice bearing
      experimental tumor and inflammation.
AB  - Discriminative detection of tumor and inflammation was tried by radio-imaging of
      hepatic uptake of 65Zn. This closely related to the level of metallothionein (MT)
      and reflected the extent of tumor growth in mice and rats transplanted with
      experimental tumor. The elevation of 65Zn distribution in liver of experimental
      tumor-bearing mice was inhibited by treatment with Zn-deficient diet, while
      stimulated by dexamethasone. This stimulation occurred 2 days after tumor
      transplantation, at which time 67Ga-citrate could not image the tumor. On the
      other hand, hepatic distribution of 65Zn was also elevated in mice by inducing
      experimental abscess, although the effect of both treatments on this elevation
      was different from the case of tumor; the elevation was inhibited by treatment
      with dexamethasone. These results suggest that radio-imaging of hepatic Zn uptake
      with a short-life gamma emitting isotope such as 69mZn with use of dexamethasone,
      if required, may be useful for a preliminary test to detect early-stage malignant
      disease.

PMID- 7735165
TI  - Simple rapid hydrolysis of acetyl protecting groups in the FDG synthesis using
      cation exchange resins.
AB  - A new solid phase method for hydrolysis of acetyl groups from the intermediate 2
      [18F]fluoro-2-deoxyglucose tetraacetate ([18F]FDG-Ac4) was developed. Fast
      cleavage occurs with Dowex 50 sulfonic acid resin (H+ form) at approximately 100
      degrees C in the absence of bulk water. [18F]FDG-Ac4 reaction mixtures were
      efficiently converted to neutral aqueous solutions of pure FDG in 10-15 min. The
      method avoids problems associated with liquid acids and can be easily integrated
      into existing [18F]FDG procedures.

PMID- 7735166
TI  - Effect of "co-ligand" on the biodistribution of 99mTc-labeled hydrazino nicotinic
      acid derivatized chemotactic peptides.
AB  - Hydrazinonicotinamide (HYNIC) derivatized chemotactic peptides radiolabeled with
      99mTc- (via 99mTc-glucoheptonate) have been demonstrated to be useful for
      infection imaging [J. Nucl. Med. 34, 1964-1974 (1993)]. Since HYNIC can occupy
      only two sites of the technetium co-ordination sphere, the labeled product most
      probably contains additional ligands. Thus we hypothesized that glucoheptonate
      serves this role by acting as a "'co-ligand'". Due to the low molecular weight of
      the chemotactic peptides, the "co-ligand" used for technetium labeling could have
      profound effects on biodistribution. To evaluate this possibility, we measured
      the biodistribution of 99mTc-labeled For-MLFK-HYNIC radiolabeled using four
      different "co-ligand"s: glucarate, glucoheptonate, mannitol and glucamine,
      providing a small series of hydroxyl-backbone ligands which differ in the number
      and type of ionizable functional groups present. Each preparation was injected
      into groups of 6 rats (approximately 10 microCi/rat) and biodistribution was
      determined at 5, 30, 60 and 120 min. Although small differences in
      biodistribution were detected in most tissues, the most prominent differences (P
      < 0.01) were observed in lung (glucoheptonate, glucarate > mannitol >>
      glucamine), liver (glucarate, glucoheptonate, mannitol >> glucamine), kidney
      (mannitol > glucarate, glucoheptonate, glucamine), spleen (glucarate >>
      glucoheptonate, mannitol >> glucamine) and GI-tract (glucarate, glucamine >>
      gluco-heptonate >> mannitol). These results provide support for the "co-ligand"
      hypothesis and indicate that the nature of the "co-ligand" can have profound
      effects on biodistribution. Although radiolabeling using glucamine as the "co
      ligand" results in the lowest concentrations of radioactivity in most organs, the
      extremely low concentration of mannitol-labeled peptide in the GI-tract suggests
      that this may be the "co-ligand" of choice for most applications.

PMID- 7735167
TI  - Synthesis of a 11C-labeled NK1 receptor ligand for PET studies.
AB  - Changes in substance P (SP) receptor concentration have been implicated in
      neuropsychiatric disorders, Parkinson's disease, arthritis, inflammatory bowel
      disease and asthma. Since, SP and peptide analogs are rapidly metabolized and do
      not penetrate into the CNS, they are not useful for PET. Recently, a non-peptide
      SP antagonist, (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP
      99,994) was developed. As a prelude to PET studies, this compound was
      radiolabeled with 11C and biodistribution was determined in hamsters. CP-99,994
      was radiolabeled by methylation of tert-Boc, desmethyl CP-99,994 with 11CH3I
      followed by deprotection and HPLC purification. The time required for the
      synthesis was 40 min from the end of bombardment. Radiochemical purity of the
      final product was > 95% and specific activity was routinely > 1000 mCi/mumol
      [EOS]. The biodistribution of 11C-CP-99,994 was determined in groups of six
      Syrian hamsters at 5 and 30 min after injection. The results of these studies
      demonstrated that significant concentrations (%ID/g +/- SEM) of CP-99,994
      accumulate in most tissues of the hamster. The highest levels of drug were
      detected in the lung: 21.04 +/- 1.26 (5 min) and 13.49 +/- 1.71 (30 min). Brain
      accumulation was: 1.44 +/- 0.06 (5 min), 1.32 +/- 0.05 (30 min). These results
      indicate that 11C-CP-99,994 can be prepared in high purity and specific activity.
      This new radiopharmaceutical may be useful for studying both central and
      peripheral SP receptors by PET.

PMID- 7735168
TI  - Synthesis of polymer-bound 6-thiolatomercury and 6-mercuric sulfonate DOPA
      precursors and their halodemercuration reactivity.
AB  - Fluorodemercuration has the greatest utility for the preparation of 6-[18F]DOPA,
      but requires separation from unreacted mercury precursor and other mercury
      containing compounds. One approach is the development of a polymer-bound mercury
      precursor. In this study, polymer-bound 6-thiolatomercury and 6-mercuric
      sulfonate DOPA derivatives, and its monomeric analogs were synthesized.
      Fluorodemercuration of monomeric analog of mercuric sulfonate gave half the yield
      (14-15%) while iododemercuration gave the same yield (38%) compared with a 6
      mercuric trifluoroacetate protected DOPA. The mercuric sulfonate undergoes
      halodemercuration, so polymer-bound halodemercuration precursors may be useful as
      precursors of 6-[18F]DOPA.

PMID- 7735169
TI  - Quantitation of 211At in small volumes for evaluation of targeted radiotherapy in
      animal models.
AB  - We have evaluated SPECT and two planar imaging methods, geometric mean (GM) and
      buildup factor (BF), for their potential to quantitate in vivo 211At
      distributions in rat spinal subarachnoid spaces using phantom studies. The use of
      medium-energy collimators and the small diameter (3 mm) of the subarachnoid space
      complicate quantitation. Net activities from distributions in various backgrounds
      were obtained using a large region of interest with background subtraction.
      Results showed quantitation accuracy within 10% for SPECT and BF in low
      backgrounds increasing to 25% at higher background levels while GM errors ranged
      from 20 to 45%. We have also obtained images of [211At]astatide distributions,
      administered intrathecally, in rats.

PMID- 7735170
TI  - A single-injection, two-sample method for measuring renal 99mTc-MAG3 clearance in
      both children and adults.
AB  - We present a method for estimating 99mTc-MAG3 clearance from both a single
      injection and two blood samples that is valid for both adults and children. It
      was obtained by fitting a scaled two-compartment model (having only two
      adjustable parameters) to adult and pediatric data from multiple centers.

PMID- 7735171
TI  - No-carrier-added meta-[123I]iodobenzylguanidine: synthesis and preliminary
      evaluation.
AB  - No-carrier-added [123I]MIBG was prepared from 3-(trimethylsilyl)benzylguanidine
      in 80-90% yield. Binding of this tracer to SK-N-SH human neuroblastoma cells
      maintained a constant level of > 50% over 2-3 log activity range. In comparison,
      the binding of [123I]MIBG prepared by isotopic exchange steadily decreased with
      dose. Biodistribution studies in normal mice demonstrated maximal concentrations
      in heart and adrenals for both preparations. In heart, significant 1.5-3.0 times
      higher levels (P < 0.05) were seen for the no-carrier-added preparation.
      Radiation dosimetry calculations suggest that the no-carrier-added preparation
      would increase the dose received by several tissues, most notably the heart where
      a 91% increase in dose is predicted.

PMID- 7735172
TI  - Synthesis of (2-[11C]methoxy)rotenone, a marker of mitochondrial complex I
      activity.
AB  - Recent studies suggest that defects in the function of the complexes of the
      electron transport chain might be involved in the pathology of neurological
      diseases such as mitochondrial encephalopathies, Parkinson's, Huntington's and
      Alzheimer's disease. Rotenone is a potent reversible competitive inhibitor of
      complex I (NADH-CoQ reductase). To study the possible involvement of complex I in
      such diseases, we synthesized (2-[11C]methoxy)rotenone by [11C]alkylation of 2-O
      desmethyl rotenone methyl enol ether followed by hydrolysis of the enol ether to
      the ketone using aqueous trifluoroacetic acid. (2-[11C]Methoxy)rotenone was
      purified by high pressure liquid chromatography (silica gel) and was obtained in
      7-10% yields decay corrected to end of bombardment in synthesis times typically
      shorter than 48 min. Radiochemical purities were over 95% and specific activities
      averaged 1000 Ci/mmol at end of synthesis.

PMID- 7735173
TI  - Kinetics of platelets in dogs with thrombocytopenia induced by antiglycoprotein
      IIb/IIIa receptor monoclonal antibody.
AB  - To experimentally assess the kinetics of platelets in thrombocytopenia, we
      constructed a canine model using 111In-oxine labeled autologous platelets and an
      intact antiplatelet monoclonal antibody (MAb) NNKY2-11 (IgG2a). With the infusion
      of radiolabeled autologous platelets into dogs, the peripheral platelet count and
      blood radioactivity level were examined, and the radioactivity in the liver,
      spleen and heart was determined with scintigraphic analysis. Thereafter, i.v.
      injection of 100 micrograms/kg of NNKY2-11 had no effect on platelet counts or
      the biodistribution of radiolabeled platelets. However, 200 and 300 micrograms/kg
      of MAb reduced the platelets, and the radioactivity of the liver and spleen
      augmented clearly after injection of MAb. Platelet radioactivity in serum, which
      had decreased after MAb infusion, did not recover, even when peripheral platelet
      counts returned to the normal levels, indicating that these new platelets might
      be derived from the platelet-storage pool or new thrombocytogenesis. This model
      of antiplatelet MAb induced thrombocytopenia seems to be useful for analyzing the
      kinetics of platelets in thrombocytopenia.

PMID- 7735174
TI  - In vitro and in vivo evaluation of streptavidin immunoconjugates of the second
      generation TAG-72 monoclonal antibody CC49.
AB  - Streptavidin was conjugated to the second-generation TAG-72 monoclonal antibody
      CC49 at lysine amino acids, oxidized carbohydrates or reduced disulfides on the
      immunoglobulin. The streptavidin immunoconjugates were radiolabelled with 111In
      DTPA-biocytin and their immunological characteristics evaluated in vitro and in
      vivo. FPLC analysis showed a single peak (mol. wt > 350 kDa) for the lysine
      conjugate and sulfhydryl conjugate (mol. wt approximately 210 kDa) but multiple
      peaks (approximately 210 to > 350 kDa) for the carbohydrate conjugate. There were
      only small differences in immunoreactivity against bovine submaxillary mucin in
      vitro. However, in mice bearing subcutaneous LS174T tumours, the lysine conjugate
      exhibited significantly lower tumour uptake (< 2% i.d./g) compared to the other
      streptavidin-CC49 conjugates (10-40% i.d./g) or DTPA-CC49 (14-18% i.d./g). Due to
      the monomeric nature and smaller molecular size of the sulphhydryl conjugate, and
      its similar in vitro and in vivo characteristics compared with DTPA-CC49, this
      conjugate has been selected for future pretargeting studies with 111In and 90Y
      biotin.

PMID- 7735175
TI  - Calculated and TLD-based absorbed dose estimates for I-131-labeled 3F8 monoclonal
      antibody in a human neuroblastoma xenograft nude mouse model.
AB  - Preclinical evaluation of the therapeutic potential of radiolabeled antibodies is
      commonly performed in a xenografted nude mouse model. To assess therapeutic
      efficacy it is important to estimate the absorbed dose to the tumor and normal
      tissues of the nude mouse. The current study was designed to accurately measure
      radiation does to human neuroblastoma xenografts and normal organs in nude mice
      treated with I-131-labeled 3F8 monoclonal antibody (MoAb) against
      disialoganglioside GD2 antigen. Absorbed dose estimates were obtained using two
      different approaches: (1) measurement with teflon-imbedded CaSO4:Dy mini
      thermoluminescent dosimeters (TLDs) and (2) calculations using mouse S-factors.
      The calculated total dose to tumor one week after i.v. injection of the 50
      microCi I-131-3F8 MoAb was 604 cGy. The corresponding decay corrected and not
      corrected TLD measurements were 109 +/- 9 and 48.7 +/- 3.4 cGy respectively. The
      calculated to TLD-derived dose ratios for tumor ranged from 6.1 at 24 h to 5.5 at
      1 week. The light output fading rate was found to depend upon the tissue type
      within which the TLDs were implanted. The decay rate in tumor, muscle,
      subcutaneous tissue and in vitro, were 9.5, 5.0, 3.7 and 0.67% per day,
      respectively. We have demonstrated that the type of tissue in which the TLD was
      implanted strongly influenced the in vivo decay of light output. Even with decay
      correction, a significant discrepancy was observed between MIRD-based calculated
      and CaSO4:Dy mini-TLD measured absorbed doses. Batch dependence, pH of the tumor
      or other variables associated with TLDs which are not as yet well known may
      account for this discrepancy.

PMID- 7735176
TI  - alpha-Methylene and glycidic acid analogs of IPPA as potential myocardial imaging
      agents.
AB  - Using organozinc cross-coupling reactions, two radiolabeled analogs of 15-(p
      iodophenyl) pentadecanoic acid (IPPA) have been designed and synthesized as
      potential scintigraphic imaging agents for the heart. Both 15-(4-iodophenyl)
      tridecylglycidic acid and 15-(4-iodophenyl)-2-methylene pentadecanoic acid were
      synthesized and radioiodinated. In tissue biodistribution studies in rats, only
      the alpha-methylene derivative of IPPA displayed a consistently higher heart to
      blood ratio and a substantially lower degree of thyroid accumulation than did
      IPPA alone. With respect to a scintigraphic imaging efficacy, the alpha-methylene
      analog of IPPA and IPPA itself showed essentially equivalent cardiac imaging
      profiles in rabbits, with a slight extension in imaging time for the alpha
      methylene analog of IPPA.

PMID- 7735177
TI  - Study finds AZT reduces HIV transmission rate from mother to infant.

PMID- 7735178
TI  - Nursing research and public policy: an essential partnership.

PMID- 7735179
TI  - Ask the experts. Who should help parents make treatment decisions about their
      newborns?

PMID- 7735180
TI  - AWHONN's silver anniversary.

PMID- 7735181
TI  - Nursing plus networking equals success for AWHONN entrepreneur.

PMID- 7735182
TI  - Ask the experts. Is suppression of lactation in postpartum patients still an
      indication for the use of bromocriptine mesylate (Parlodel)?

PMID- 7735183
TI  - AWHONN's silver anniversary.

PMID- 7735184
TI  - AWHONN's silver anniversary.

PMID- 7735185
TI  - Implementing research with underserved populations.

PMID- 7735186
TI  - Ask the experts. What is "informed consent"?

PMID- 7735188
TI  - Repeat cesarean section vs. VBACs: helping women decide.

PMID- 7735187
TI  - AWHONN's silver anniversary.

PMID- 7735189
TI  - Ask the experts. What are antiphospholipid antibodies and what is their
      significance in pregnancy?

PMID- 7735190
TI  - AWHONN's silver anniversary.

PMID- 7735191
TI  - Committee to Advise on Tropical Medicine and Travel (CATMAT). Statement on
      meningococcal vaccination for travellers.

PMID- 7735192
TI  - Isoniazid chemoprophylaxis for dual HIV-TB infection: a cautionary tale.

PMID- 7735193
TI  - Tissue and subcellular distribution of bound and acid-labile sulfur, and the
      enzymic capacity for sulfide production in the rat.
AB  - The tissue and subcellular distribution in liver and kidney of bound and acid
      labile sulfur as well as the enzyme capacity for sulfide production related to
      the desulfuration pathway were determined in rats. Bound sulfur was widely
      distributed in tissues and highest in kidney, whereas acid-labile sulfur was
      highest in heart. Bound sulfur was found primarily in the cytosolic fraction in
      the form of high molecular weight material in liver, and as both high and low
      molecular weight material in kidney. Acid-labile sulfur was located in the
      mitochondrical fraction. Sulfide production capacity from cysteine was greatest
      in liver cytosol. This capacity was well correlated with the distribution of
      gamma-cystathionase in tissues and subcellular fractions.

PMID- 7735194
TI  - Studies on thermophile products. XI. Biological effect of antigen presenting
      inhibitor, isofatty acid-containing phosphatidylethanolamine, on mouse
      macrophages.
AB  - A new fraction, Fr. 8-A, which consists of a phosphatidylethanolamine with C14:0
      C18:0 isofatty acids was obtained from Bacillus stearothermophilus UBT8038. The
      fraction inhibited major histocompatibility complex class II (Ia) antigen
      expression and antigen presentation on mouse macrophages. The effect of Fr.8-A on
      macrophage functions related to antigen presentation was investigated. Fr. 8-A
      increased arachidonate release, prostaglandin (PG) E2 release and nitrite
      production from peritoneal macrophages. It increased further the levels of PGE2,
      nitrite and tumor necrosis factor in the culture supernatant of the macrophages
      induced by the supernatant from concanavalin A-stimulated spleen cell cultures.
      Fr. 8-A augmented the activity of peritoneal macrophages to suppress Con A
      stimulated T cell proliferation. Addition of either indomethacin or Ng-methyl-L
      arginine had no effect on the augmentation of suppressor macrophage activity or
      the inhibition of antigen presentation by Fr. 8-A, while simultaneous addition of
      both inhibitors abrogated the effect of the fraction. These results indicate that
      Fr. 8-A inhibits Ia expression and antigen presentation, and augments suppressor
      macrophage activity at least partly via the activation of both cyclooxygenase and
      nitric oxide synthase pathways.

PMID- 7735195
TI  - Characterization of an acidic polysaccharide with immunological activities from
      the tuber of Pinellia ternata.
AB  - An acidic polysaccharide, called pinellian PA, was isolated from the tuber of
      Pinellia ternata Breit. It was homogeneous on electrophoresis and gel
      chromatography, and its molecular mass was estimated to be 11.8 x 10(4).
      Pinellian PA is composed of L-arabinose: D-galactose: L-rhamnose: D-galacturonic
      acid: D-glucuronic acid in the molar ratio of 5:15:1:3:3, in addition to small
      amounts of O-acetyl groups and peptide moieties. Reduction of carboxyl groups,
      methylation analysis and nuclear magnetic resonance studies show that the core
      structural features include a backbone chain composed of beta-1,3-linked D
      galactose units. Some of the galactose units in the backbone carry beta-1,6
      linked D-galactosyl side-chains at position 6. Pinellian PA produces significant
      potentiation of the reticuloendothelial system, as shown by a carbon clearance
      test, and also exhibits potent anti-complementary activity.

PMID- 7735196
TI  - The inhibitory effects of tea polyphenols (flavan-3-ol derivatives) on Cu2+
      mediated oxidative modification of low density lipoprotein.
AB  - Tea polyphenols (flavan-3-ol derivatives) suppressed the oxidative modification
      of low density lipoprotein (LDL) which is assumed to be an important step in the
      pathogenesis of atherosclerosis lesions. Inhibitory experiments on the oxidative
      impairment of porcine serum LDL by flavan-3-ols were carried out by incubating
      them at 37 degrees C in the presence of 5 microM Cu2+. The oxidation of LDL was
      monitored either by an absorption increase at 234 nm due to the conjugated diene
      formation, or the formation of hydroperoxides and thiobarbituric acid reactive
      substances (TBARS). It was found that the oxidation was strongly inhibited by
      various flavan-3-ols, and a lag time over 100 min appeared, depending on the
      types of flavan-3-ols used. The activities based on the prolongation of the lag
      time were in the order of (-)-epigallocatechin (EGC) < (+)-catechin (C) < (-)
      epicatechin (EC) < (-)-epicatechingallate (ECG) < (-)-epigallocatechingallate
      (EGCG). IC50 of flavan-3-ols on Cu2+ mediated hydroperoxides and TBARS formation
      of LDL were 0.90, 0.95 microM for ECG and 2.38, 2.74 microM for EGC,
      respectively. It was found that the Cu2+ mediated cholesterol ester degradation
      in LDL was almost completely inhibited by 5.0 microM C or EGCG. Cu2+ mediated
      apolipoprotein B-100 fragmentation was also inhibited (up to 60%) in the presence
      of C or EGCG.

PMID- 7735197
TI  - Enzymic studies on the animal and intestinal bacterial metabolism of geniposide.
AB  - Geniposide, a main iridoid glucoside of Gardenia fruit, is transformed to
      genipin, a genuine choleretic, in vivo in rats (Aburada et al., J. Pharmacobio
      Dyn., 1, 81 (1978)). As geniposide was not hydrolyzed to any metabolite by rat
      liver homogenate, which has beta-D-glucosidase and esterase activities, beta-D
      glucosidases in intestinal bacteria seem to be required for an exhibition of its
      choleretic action. The crude extract of Eubacterium sp. A-44, a human intestinal
      anaerobe, hydrolyzed geniposide, but that of Ruminococcus sp. PO1-3, another
      human anaerobe, did not, though both extracts had beta-D-glucosidase activities
      for p-nitrophenyl beta-D-glucopyranoside. Only one of three beta-D-glucosidases
      from E. sp. A-44 and none of two from R. sp. PO1-3 hydrolyzed geniposide to
      genipin. However, carboxylesterases from E. sp. A-44 and pig liver were unable to
      hydrolyze geniposide to geniposidic acid, but hydrolyzed genipin to an aglycone
      of geniposidic acid, indicating that geniposide is first hydrolyzed to genipin by
      beta-D-glucosidases and subsequently to the aglycone of geniposidic acid by
      esterases. Thus, when geniposide is orally administered, genipin seems to be
      effectively produced in the intestine and then absorbed to act as a genuine
      choleretic.

PMID- 7735198
TI  - Anti-inflammatory effects of etodolac: comparison with other non-steroidal anti
      inflammatory drugs.
AB  - The anti-inflammatory effects of etodolac (Eto) were compared with those of 6
      other anti-inflammatory drugs: indomethacin (Ind), diclofenac Na (Dic), piroxicam
      (Pir), naproxen (Nap), ketoprofen (Ket) and aspirin (Asp). Eto inhibited
      carrageenin-induced edema in rats, adjuvant-induced arthritis in rats, acetic
      acid-induced writhing in mice and brewer's yeast-induced hyperalgesia and fever
      in rats. In the adjuvant arthritis test, the ED30 value (1.88 mg/kg) on day 3 and
      ED50 values (adjuvant-injected paw: 1.18 mg/kg and non-injected paw: 0.96 mg/kg)
      on day 18 for Eto were comparable to those for Dic (2.16, 1.72 and 1.28) when
      given prophylactically and the ED50 values for Eto (adjuvant-injected paw: 1.61
      and non-injected paw: 1.20 mg/kg) were comparable to those for Ket (1.24 and
      1.22) when used therapeutically. The analgesic activity of Eto (ED50 value: 3.67
      mg/kg) in the acetic acid-induced writhing test was greater than that of Nap
      (9.83) or Asp (31.6) and less than that of Ind (0.71), Dic (1.54), Pir (0.92) or
      Ket (1.34). In the antipyretic test, the minimum effective dose (MED: 1 mg/kg)
      for Eto was comparable to that for Ind (1.0), Nap (1.0) or Ket (1.0). Eto was
      less potent in inhibiting carrageenin-induced edema (ED30 value: 6.99 mg/kg) and
      inflammatory pain (ED50 value: 9.24 mg/kg) than the other drugs (Ind: 2.32 and
      3.47, Dic: 0.69 and 3.80, Pir: 1.31 and 1.94, Nap: 1.83 and 2.78, Ket: 1.12 and
      0.63), except for Asp (167 and 51.8).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735199
TI  - Purification and characterization of cytochrome P450 3A enzyme from hepatic
      microsomes of untreated doguera baboons.
AB  - We isolated a form of cytochrome P450 (P450) from hepatic microsomes of untreated
      doguera baboons. The final preparation (referred to as P450 BLa) was apparently
      homogenous, as judged by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The estimated minimum molecular weight of P450 BLa was 50 kDa.
      The N-terminal amino acid sequence of P450 BLa (identified 10 residues) was
      identical with that of P450 3A8 purified from cynomolgus monkeys. This protein
      was cross-reactive with antibodies raised against P450 3A4 and P450 CMLc which
      were P450 3A enzymes purified from hepatic microsomes of humans and cynomolgus
      monkeys, respectively. P450 BLa was capable of catalyzing testosterone 6 beta
      hydroxylation and zonisamide reduction. P450 BLa antibody inhibited the activity
      of testosterone 6 beta-hydroxylase, but not the activities of testosterone 16
      alpha- and 16 beta-hydroxylases in liver microsomes of doguera baboons. From
      these lines of evidence we conclude that P450 BLa can be classified as part of
      the P450 3A subfamily and acts as a constitutive testosterone 6 beta-hydroxylase
      in hepatic microsomes of doguera baboons.

PMID- 7735200
TI  - Prolongation of life span and improved learning in the senescence accelerated
      mouse produced by aged garlic extract.
AB  - The effects of aged garlic extract (AGE) on longevity and learning and memory
      performances were studied in the senescence accelerated mouse (SAM). A solid diet
      containing 2% (w/w) AGE was given to SAM from 2 months of age. The survival ratio
      of SAM P8, senescence accelerated animals, treated with AGE was significantly
      higher than that of untreated controls. AGE, however, did not affect the life
      span of SAM R1, a senescence-resistant strain. AGE had no effect on body weight
      and motor activity. In the passive and conditioned avoidance tests, AGE markably
      improved a memory acquisition process in the step-down and shuttle-box tests, and
      also a retention process in the step-through and step-down tests in SAM P8. The
      beneficial effects of AGE were observed in a memory retention process in the step
      down test and in an acquisition stage in lever-press test in SAM R1. These
      results suggest the possibility that AGE might be useful for treating
      physiological aging and age-related memory deficits in humans.

PMID- 7735201
TI  - Involvement of protease inhibitors in staphylokinase-induced fibrin-specific
      fibrinolysis.
AB  - We compared the fibrinolytic properties of recombinant staphylokinase (SAK), a
      fibrin-specific plasminogen activator, with those of streptokinase and tissue
      type plasminogen activator (t-PA) by means of the amidolytic method. We also
      investigated the involvement of alpha 2-macroglobulin, C1-inactivator and alpha 1
      antitrypsin in SAK-induced fibrin-specific fibrinolysis. Both SAK and t-PA
      activated plasminogen efficiently in the presence of fibrin in human plasma.
      Although t-PA activated plasminogen dependently on fibrin in the reconstituted
      plasma system, SAK activated plasminogen independently of fibrin without alpha 2
      plasmin inhibitor (alpha 2-antiplasmin, alpha 2-PI). These findings suggest that
      fibrin and alpha 2-PI play important roles in plasminogen activation by SAK but
      not by t-PA. Furthermore, protease inhibitors such as alpha 2-PI, alpha 2
      macroglobulin, C1-inactivator and alpha 1-antitrypsin inhibited plasminogen
      activation by SAK and the inhibitory actions of these protease inhibitors
      disappeared in the presence of fibrin. This shows that alpha 2-macroglobulin, C1
      inactivator and alpha 1-antitrypsin, other than alpha 2-PI, contribute to the
      fibrin-specificity of SAK.

PMID- 7735202
TI  - Diuretic effects of KW-3902, a novel adenosine A1-receptor antagonist, in
      anesthetized dogs.
AB  - The effects of intravenous infusion of KW-3902 (8-(noradamantan-3-yl)-1,3
      dipropylxanthine), a novel adenosine A1-receptor antagonist, on urine volume,
      urinary excretion of electrolytes and renal hemodynamics were examined in
      anesthetized dogs. KW-3902 at 10 and 30 micrograms/kg/min for 20 min inhibited
      the decline of renal blood flow induced by intrarenal arterial injection of
      adenosine (0.5-2.0 micrograms). KW-3902 at these doses produced significant
      increases in urine volume and sodium excretion with little change in potassium
      excretion. The diuretic effect of KW-3902 at 30 micrograms/kg/min for 20 min
      continued for longer than 1 h even after discontinuation of the KW-3902 infusion.
      KW-3902 did not affect creatinine clearance, renal blood flow, arterial blood
      pressure or heart rate. Furosemide at 10 micrograms/kg/min for 20 min brought
      about significant increases in urine volume and excretion of sodium and
      potassium. The diuresis and saliuresis induced by furosemide continued for only
      40 min after discontinuation of the drug infusion. Trichlormethiazide at 3
      micrograms/kg/min for 20 min also provoked increases in urine volume and sodium
      excretion, but did not affect potassium excretion. The diuretic and natriuretic
      effect of trichlormethiazide gradually disappeared after discontinuation of the
      drug infusion. The present study in anesthetized dogs suggests that KW-3902, an
      adenosine A1-receptor antagonist, produces diuresis and natriuresis but not
      kaliuresis and that the diuresis and natriuresis are caused in large part by the
      inhibition of sodium reabsorption at tubular sites.

PMID- 7735203
TI  - Promotion of neuronal differentiation of PC12h cells by natural lignans and
      iridoids.
AB  - We studied the effect of (+)- and (-)-syringaresinol, (+)-syringaresinol
      glucosides, syringin, aucubin and catalpol on neurite outgrowth of a cultured
      cell line of paraneuron, PC12h cells. Of these compounds, (+)-syringaresinol
      diglucoside and partly glucosidase-hydrolyzed aucubin were found to be the most
      potent in promotion of the neurite outgrowth and stimulated responses to a high
      concentration of KCl and to carbachol in the cells, as observed by increase of
      the concentration of cytosolic free calcium. It is suggested that some of these
      herb-derived compounds can induce neuronal differentiation in PC12h cells.

PMID- 7735204
TI  - Mechanism of testicular atrophy induced by Di-n-butyl phthalate in rats. VI. A
      possible origin of testicular iron depletion.
AB  - In previous studies we have described mechanisms of testicular atrophy whereby di
      n-butyl phthalate (DBP) caused a sloughing of the germ cells, prior to the
      testicular atrophy; this sloughing might be attributed to iron depletion in the
      blood and the testicular interstitial cells. To determine whether the iron
      depletion is mediated by iron-release from hemoglobin (Hb), the effects of DBP
      upon erythrocytes have been studied. In the in vivo studies, it was observed that
      DBP induced glutathione (GSH) depletion, a decrease in GSH reductase activity and
      Heinz body formation in the red blood cells, and iron-release from Hb. In the in
      vitro studies, in which mono-n-butyl phthalate (MBP), a metabolite of DBP, was
      incubated with erythrocytes, Heinz bodies and iron release from Hb were observed.
      The present study proposes that a mechanism for the testicular atrophy induced by
      DBP might involve Heinz body formation, accompanied by iron release from Hb
      followed by depletion of iron in the blood and testes.

PMID- 7735205
TI  - Procyanidins from tormentil: fractionation and study of the anti-radical activity
      towards superoxide anion.
AB  - A standardised water-soluble extract was prepared from rhizomes of Potentilla
      tormentilla. The procyanidins in the extract were fractionated according to their
      degree of polymerisation by chromatography on Sephadex LH20. The anti-radical
      activities of the different fractions towards superoxide anion were compared when
      pentamers and hexamers were found to be the most active.

PMID- 7735206
TI  - Pharmacokinetic and pharmacodynamic studies of L-dopa in rats. I. Pharmacokinetic
      analysis of L-dopa in rat plasma and striatum.
AB  - The purpose of this investigation was to quantitatively describe the
      pharmacokinetics of exogenous and endogenous L-dopa in plasma and the striatum
      using a basic physiological model, and to determine the apparent metabolism
      clearance from L-dopa to dopamine in the striatum. Male Wistar rats were used in
      this study. The time courses of L-dopa concentrations in plasma and the striatum
      were determined before and after the rapid i.v. injection of 10, 50 and 100
      mg/kg. Plasma and striatum samples were obtained over 480 min (17 time points)
      from different group of animals and then assayed by HPLC-ECD. The endogenous L
      dopa concentration in plasma before drug administration was 2.1 +/- 0.6 mg/l. The
      exogenous L-dopa concentration declined biexponentially with time after drug
      injection. The total clearance of exogenous L-dopa in plasma was 3.13(l/h)/kg.
      The production rate constant of endogenous L-dopa in plasma was 6.59(mg/h)/kg.
      The value of the production rate constant of endogenous L-dopa in plasma could be
      calculated by the multiplication of the total clearance of L-dopa and the
      endogenous L-dopa concentration in plasma before drug injection. The
      pharmacokinetics of endogenous and exogenous L-dopa in plasma could be described
      quantitatively by a two compartment model which included the production rate
      constant of endogenous L-dopa. The time course of L-dopa concentrations in the
      striatum was analyzed on a hybrid model in which the striatum compartment is
      independently connected with the plasma compartment by the apparent diffusion
      clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735207
TI  - Pharmacokinetic and pharmacodynamic studies of L-dopa in rats. II. Effect of L
      dopa on dopamine and dopamine metabolite concentration in rat striatum.
AB  - The purpose of this investigation was to quantitatively describe the time courses
      of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      concentrations in the striatum after L-dopa injection using a constructed
      dopamine metabolism model. The time courses of dopamine, DOPAC and HVA
      concentration in the striatum of rats was determined before and after the rapid
      i.v. injection of 10, 50 and 100 mg/kg using the same animals as in the previous
      report. The endogenous dopamine, DOPAC and HVA concentrations in the striatum
      before L-dopa administration were 5.9 +/- 0.7 micrograms, 3.6 +/- 0.4 micrograms
      and 1.0 +/- 0.2 micrograms/g, respectively. The dopamine concentration in the
      striatum increased immediately after L-dopa injection, with the peak
      concentration (15.9 +/- 0.5 micrograms/g) occurring at 3 min; then it returned to
      the pre-medication level until 2 h at 100 mg/kg dosing. The time course of
      dopamine concentration in the striatum was analyzed on a constructed dopamine
      metabolism model which has a zero-order production rate for the production of
      dopamine (i.e. release from the dopamine neuronal terminals) and two apparent
      first-order clearance terms, one from L-dopa to dopamine, which was estimated in
      the previous report, and the other from dopamine to dopamine metabolites (DOPAC
      and HVA). However, the time course of dopamine concentration in the striatum
      could not be described by this model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735208
TI  - In vivo microdialysis for pharmacokinetic investigations: a plasma protein
      binding study of valproate in rabbits.
AB  - The use of microdialysis to study the binding of valproate (VPA) to plasma
      proteins was evaluated in rabbits. Prior to an in vivo microdialysis, in vitro
      relative recovery of VPA respectively from Ringer's solution, 5% (w/v) of albumin
      solution and plasma sample via a microdialysis probe was examined. The in vitro
      relative recovery was defined as a ratio of the VPA concentration determined in
      the dialysate to the free VPA concentration in the sample solution surrounding
      the membrane of the microdialysis probe. When the sample solution was well
      stirred at 700 rpm and maintained at 37 degrees C, the in vitro relative recovery
      of VPA was significantly different among them. It increased in the order of
      Ringer's solution (34.3 +/- 2.6%) > 5% (w/v) of albumin solution (25.7 +/- 4.6%)
      > rabbit plasma sample (15.8 +/- 1.2%). Thereafter, pharmacokinetics of VPA was
      determined using both microdialysis sampling via the rabbit femoral vein and
      collection of whole blood via the rabbit ear vein after intravenous
      administration of VPA at a dose of 43 mg/kg. Free concentrations of VPA in plasma
      were determined by ultrafiltration method as opposed to microdialysis method.
      There was no difference in the elimination half-life of VPA determined by
      microdialysis, 1.09 +/- 0.22 h, or ultrafiltration, 1.22 +/- 0.21 h. The AUC of
      VPA in dialysate was 15 +/- 4 micrograms.h/ml, which corresponded to 15% of that
      in ultrafiltrate (103 +/- 17 micrograms.h/ml). The value was in good agreement
      with the in vitro relative recovery of VPA from plasma sample (15.8 +/-
      1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735209
TI  - Isotopic fractionation of isopropylantipyrine and its deuterated analogues by
      capillary gas chromatography.
AB  - Isotopic fractionation of isopropylantipyrine (IPA) and its deuterated analogues
      was examined by gas chromatography (GC) using capillary column. The separation of
      IPA and seven kinds of deuterated IPAs were proportional to the number of labeled
      deuterium atoms and inversely to the temperature of the column oven. The
      resolution coefficient between IPA and IPA-3-C2H3-4-(C2H3)2 (IPA-2H-7) was 1.46
      at 200 degrees C for column temperature. The present isotopic fractionation
      procedure was applied to the isotope dilution analysis of IPA. Measurement of the
      sample prepared by the addition of a known amount of IPA and IPA-2H-7 to the
      control plasma of rabbit allowed observation of a linear relationship between
      peak area ratio and added amount ratio. The correlation coefficient obtained by
      regression analysis was 1.000. The present method was also applied to determine
      the plasma level of IPA in rabbit after oral administration.

PMID- 7735210
TI  - Effect of skin surface lipid on the skin permeation of lidocaine from pressure
      sensitive adhesives.
AB  - Pressure sensitive adhesives (PSA) tapes containing different concentrations of
      lidocaine were prepared by a general casting method using styrene-isoprene
      styrene block copolymer, and the in vitro skin permeation of lidocaine from each
      tape was evaluated using diffusion cell and excised hairless rat skin. The skin
      permeation was proportionally increased by up to 40% lidocaine in the PSA tape
      and did not change after this concentration. Although the bending point of the
      steady-state flux via skin concentration curve was found at 40%, saturated
      concentration or solubility of lidocaine in the tape was estimated to be about
      20% by differential scanning calorimetry (DSC) measurement. In addition, the
      steady-state flux of lidocaine through skin from water or silicone fluid
      suspension (92 or 120 micrograms/cm2.h, respectively) was very similar to those
      of 40, 50 and 60% tapes (105, 101 and 112 micrograms/cm2.h, respectively).
      Decrease in the concentration in tapes during the permeation experiment explained
      only part of these phenomena. To analyze them further, the drug free PSA tape
      with or without (control) skin surface lipid was affixed to 50% lidocaine PSA
      tape for 48 h, and the amount of lidocaine crystal in the layered tapes was
      measured by DSC. The amount was found to be lower in the lipid-containing tape
      than in the lipid-free tape, suggesting that skin surface lipid can dissolve
      lidocaine crystal or solid in PSA tape to decrease its thermodynamic activity.
      Thus it is important to follow the concentration and thermodynamic activity of
      lidocaine in PSA tape, skin and the interface between the two layers to exactly
      assess its skin permeation flux.

PMID- 7735211
TI  - Variations in the level of urinary thiobarbituric acid reactant in healthy humans
      under different physiological conditions.
AB  - The level of urinary thiobarbituric acid (TBA) reactants in healthy human
      subjects due to malonaldehyde derivatives was measured to assess the lipid
      peroxidation status of the whole body. For each subject the TBA reactant level
      over a day varied over a 2-3 fold range while the daily level varied over a 1.5-3
      fold range under normal life-style conditions. One of the factors causing an
      increase in the reactant level within a single day may be the subjects's physical
      activity, because the reactant level of each subject was higher in the afternoon
      or in the evening than in the morning. Remaining awake all night or hard exercise
      caused a dramatic increase in the reactant level over a day and in the daily
      reactant level. The reactant level within a single day for a subject was
      increased 5.5 fold and the daily level 3 fold by remaining awake all night, and
      the level within a day was increased 22 fold by hard exercise while the
      corresponding daily level was increased 7 fold. It is unlikely that food, alcohol
      and smoking greatly affect the reactant level. The results suggest that increased
      physical activity enhances lipid peroxidation in the whole body and thus the
      increased urinary excretion of malonaldehyde derivatives.

PMID- 7735212
TI  - Influence of endotoxin and lipid A on the renal handling and accumulation of
      gentamicin in rats.
AB  - The contribution of lipid A, an active component of endotoxin (LPS), to changes
      in the pharmacokinetics, renal handling and intrarenal accumulation of gentamicin
      induced by Klebsiella pneumoniae LPS was investigated in rats. Either LPS (250
      micrograms/kg) or lipid A (equivalent to dose of LPS) was infused 2 h before the
      administration of gentamicin (10 mg/kg). The effects of LPS and lipid A on the
      intrarenal accumulation of gentamicin were also evaluated. Significant increases
      in the levels of plasma creatinine and blood urea nitrogen were observed in both
      the LPS and lipid A groups. Both LPS and lipid A induced significant decreases in
      the glomerular filtration rate (by approximately 30%) and systemic clearance of
      gentamicin (by approximately 25%). No changes in the fraction of urinary
      excretion (> 0.9) or steady-state volume of distribution of gentamicin were
      observed between either the control, LPS or lipid A groups. There were no
      significant differences among the three groups in the tubular reabsorption or
      intrarenal accumulation of gentamicin. The degree of effect of lipid A on the
      pharmacokinetics of gentamicin observed in this study was nearly equal to that of
      LPS. These results suggest that lipid A plays a major role in changes in the
      pharmacokinetics and renal handling of gentamicin induced by LPS.

PMID- 7735213
TI  - Characterization of region Ic in site I on human serum albumin.
      Microenvironmental analysis using fluorescence spectroscopy.
AB  - Characteristics of region Ic among at least three overlapping binding regions
      (regions Ia, Ib and Ic) in site I on human serum albumin (HSA) were analysed
      using n-alkyl p-aminobenzoates (n-alkyl p-ABEs), all of which are specific
      fluorescent probes for region Ic. In the interaction processes between n-alkyl p
      ABEs and HSA, hydrophobic interaction, van der Waals interaction and local
      structural changes in region Ic were found to be involved based on the results
      obtained by analyses of the fluorescence spectra, structure-activity
      relationships and thermodynamic parameters. In addition, comparison of the
      fluorescence spectra of n-alkyl p-ABEs in HSA and detergents indicated that the
      possibility of a hydrophobic region Ic around which an amino acid with cationic
      charge locates could not be denied because of the similarity of fluorescence
      spectra between n-alkyl p-ABEs in HSA and in neutral and cationic detergents. The
      deviation of n-alkyl p-ABEs with long alkyl chains (C9-C12) in the relationships
      between association constants and physicochemical properties of a series of n
      alkyl p-ABEs (C1-C12) suggested that region Ic possess an optimal depth. A
      conformational change of HSA with increasing pH (pH 6-9) generated an increase in
      hydrophobicity and adaptability of the binding region and made interaction easy,
      with an increase in adaptability of the binding region Ic; consequently, it
      enhanced the binding of n-alkyl p-ABEs to HSA.

PMID- 7735214
TI  - Time-course experiment involving glycosaminoglycan synthesis by normal human
      dermal fibroblasts cultured in the presence of dibutyryl cyclic AMP and retinoic
      acid.
AB  - Glycosaminoglycan (GAG) synthesis by cultured normal human dermal fibroblasts was
      examined. Hyaluronic acid (HA) synthesis reached a maximum on day 3 (0.3
      microgram/ml medium) and then decreased to a low level (0.15 microgram/ml
      medium). The amounts of dermatan sulfate (DS) and chondroitin sulfate (ChS)
      synthesized by the cells increased with increasing cell numbers during the
      initial stage to attain constant levels (0.092 microgram DS/ml, 0.026 microgram
      ChS/ml medium) after the cells reached confluence. We also tested the effects of
      dibutyryl cyclic AMP (dbcAMP) and retinoic acid (RA) on GAG synthesis by the
      cells. The synthesis of HA and ChS by cells was stimulated, when the cells were
      cultured in medium containing dbcAMP (0.1 mM), whereas DS synthesis was scarcely
      affected. However, addition of RA (5 mM) suppressed GAG synthesis by the cells.

PMID- 7735215
TI  - A glucan with immunological activities from the tuber of Alisma orientale.
AB  - A glucan, called alisman SI, was isolated from the tuber of Alisma orientale
      Juzepcz. It was homogeneous on electrophoresis and gel chromatography, and its
      molecular mass was 1.1 x 10(4). It is composed solely of D-glucose. Methylation
      analysis, nuclear magnetic resonance and enzymic degradation studies indicated
      that it has a high-branched glucan type structure mainly composed of alpha-1,4
      linked D-glucopyranosyl residues with partially alpha-1,6-linked units and both
      3,4- and 4,6-branching points. The polysaccharide exhibited significant
      reticuloendothelial system-potentiating activity in a carbon clearance test, as
      well as a pronounced anti-complementary activity.

PMID- 7735216
TI  - Molecular parameters for the anti-human immunodeficiency virus activity of T22
      ([Tyr5,12, Lys7]-polyphemusin II).
AB  - T22 ([Tyr5,12, Lys7]-polyphemusin II) was found to exhibit strong anti-human
      immunodeficiency virus (HIV) activity and exert its effects on a virus-cell
      fusion process. In the present study, the all-D enantiomer of T22 and its related
      compounds were synthesized to examine the molecular parameters required for the
      interaction of T22 with membrane components of cells or viruses in order to exert
      this anti-HIV activity. The anti-HIV activity of these analogs was investigated
      in comparison with their membrane permeability with aspect to large unilamellar
      vesicles (LUVs). The all-D enantiomer of T22 exhibited a 20-fold lower anti-HIV
      activity compared with T22, whereas they both showed the same membrane
      permeability. No positive correlation between anti-HIV activity and membrane
      permeability was observed. These results suggest that the anti-HIV activity of
      T22 is mediated through the interaction with chiral component(s) of the cell or
      virus.

PMID- 7735217
TI  - An ex vivo assay for estimating the antiviral state of hepatocytes.
AB  - An ex vivo antiviral assay was established which uses hepatocytes from mice given
      recombinant mouse interferon-beta (rmIFN-beta). Assay results were compared with
      results obtained with a 2',5'-oligoadenylate synthetase (2-5AS) assay. rmIFN-beta
      was intraperitoneally administered to C3H mice and the antiviral state of their
      liver parenchymal cells was evaluated in an in vitro cytopathic effect assay. In
      this assay, cells are infected with vesicular stomatitis virus (VSV) and
      surviving cells are determined colorimetrically. The antiviral state was measured
      as the resistance of hepatocytes to VSV infection with increasing doses of rmIFN
      beta. The antiviral state correlated well with the dose-dependent increase in
      hepatic 2-5AS activity. This good correlation suggests that induction of 2-5AS
      mediates the antiviral action of interferon in liver tissue. This ex vivo assay
      could be a useful tool for estimating the ability of hepatocytes to resist
      hepatitis virus infection.

PMID- 7735218
TI  - A convenient screening test for hypoxic cell radiosensitizers/cytotoxins.
AB  - A convenient in vitro screening test using E. coli B/r for evaluating a variety
      of hypoxic cell radiosensitizers/hypoxic cell cytotoxins has been developed for
      the initial selection of candidates in medicinal/organic chemistry laboratories.
      E. coli cells were used for convenience since: (1) the bacterium is grown using
      commercially available broths, where it multiplies rapidly, and requires little
      specialized equipment for growth and handling. (2) More is known about the
      genetics and biochemistry of the radiation damage to these cells and their repair
      than any other organism.

PMID- 7735219
TI  - Beneficial effects of DX-9386, a traditional Chinese prescription, on memory
      disorder produced by lesioning the amygdala in mice.
AB  - The amygdala is one of the key areas of the brain involved in learning and
      memory. Bilateral lesions of the amygdala in 9-week-old mice induced impairment
      of memory acquisition and retention. DX-9386, a traditional Chinese medicinal
      prescription consisting of ginseng, polygala, acorus and hoelen, was orally
      administered to the lesioned mice after the operation until all the experiments
      were completed. From 15d after surgery, learning behavior in the step-down test
      was observed daily for 10 d. DX-9386 treatment ameliorated the memory acquisition
      deficit. The number of step-down events in the first testing trial was
      significantly decreased by administration of 250 mg/kg of the prescription to the
      lesioned group of mice. Choline acetyltransferase activity in the cerebral cortex
      of the lesioned mice was significantly decreased, while repeated administration
      of the prescription did not affect this biochemical parameter. These results
      indicate that the memory acquisition enhancing effect of DX-9386 may not be
      achieved by direct activation of cholinergic transmission in the brain but by
      some other mechanism(s).

PMID- 7735221
TI  - Effects of various natural antioxidants on the Cu(2+)-mediated oxidative
      modification of low density lipoprotein.
AB  - We have reported in our previous paper that several flavan-3-ol derivatives (tea
      polyphenols) inhibited the Cu(2+)-mediated low density lipoprotein (LDL)
      oxidation in vitro. (-)-Epigallocatechin gallate (EGCG), in particular, exhibited
      strong inhibition. In this study, we have compared the antioxidative effects of
      EGCG with those of other natural antioxidants, such as flavonols, sesaminol,
      curcuminoid derivatives, tocopherol analogues and theaflavins. The antioxidative
      effects were monitored by conjugated diene formation in LDL which was carried out
      at 37 degrees C with 5 microM CuSO4 with or without antioxidants. Dibutyl
      hydroxytoluene (BHT) was used as a reference compound. The lag-time before the
      onset of conjugated diene formation was more than 100 min in the presence of 0.5
      microM EGCG, theaflavin, myricetin, quercetin, and sesaminol. The ability to
      prolong the lag-time was in the order of sesaminol > quercetin > EGCG >
      theaflavin > or = myricetin > BHT > alpha-tocopherol. Among the 4 tocopherol
      analogues used, alpha-tocopherol showed the strongest antioxidative activity. We
      have also studied the effects of EGCG, BHT, and alpha-tocopherol on cholesteryl
      and alpha-tocopherol on cholesteryl ester (CE) degradation and apolipoprotein B
      100 (apo B 100) fragmentation in the Cu(2+)-mediated oxidative modification of
      LDL. EGCG was the most effective inhibitor of CE degradation and apo B 100
      fragmentation.

PMID- 7735220
TI  - Atomic force microscopy of dimyristoylphosphatidylcholine membranes.
AB  - We have observed the surface images of dimyristoylphosphatidylcholine (DMPC)
      monolayer and DMPC vesicles with an atomic force microscope (AFM). It was
      confirmed that the lattice structure of polar head groups of DMPC molecules in a
      Langmuir-Blodgett monolayer is similar to those of large unilamellar DMPC
      vesicles. AFM images of small unilamellar vesicles of DMPC showed larger lattice
      structures than those of the monolayer, reflecting differences of molecular
      packing in these membranes.

PMID- 7735222
TI  - Studies on the quantitative autoradiography. III. Quantitative comparison of a
      novel tissue-mold measurement technique "paste-mold method," to the
      semiquantitative whole body autoradiography (WBA), using the same animals.
AB  - A novel preparation technique, so called "Paste Mold," was devised for organ and
      tissue distribution studies. This is the most powerful by joining with
      autoradioluminography (ARLG), which was established and validated recently in the
      working group of Forum '93 of Japanese Society for study of xenobiotics. A small
      piece (10-50 mg) of each organ or tissue was available for measuring its
      radioactive concentration and it was sampled from the remains of frozen carcass
      used for macroautoradiography (MARG). The solubilization of the frozen pieces was
      performed with mixing a suitable volume of gelatine and strong alkaline solution
      prior to mild heating kept at 40 degrees C for a few hours. After that, the
      tissue paste was molded in template pattern to form the small plates. The molded
      plates were contacted with Imaging plate (IP) for recording their radioactive
      concentration. The recorded IP was processed by BAS2000. The molded plate was
      formed in thickness of 200 microns, so called infinit thickness against soft beta
      rays, and therefore the resulting relative intensities, represented by (PSL-BG)/S
      values, indicated practically responsible ratio of the radioactive concentration
      in organs and tissues, without any calibulation for beta-self absorption
      coefficiency. On the other hand, the left half body of the frozen carcass was
      used for making whole body autoradiography (WBA) before the Paste-Mold
      preparation. Comparison was performed for difference in (PSL-BG)/S values of
      organs and tissues between frozen and dried sections. A good concordance in
      relative intensities, (PSL-BG)/S by the Paste-Mold preparation was given with
      those by the frozen sections rather than dried sections.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7735223
TI  - Studies on the quantitative autoradiography. IV. Quantitative reliability of TLC
      autoradioluminography.
AB  - Phosphor Imaging plates (IPs) with high sensitivity to both low- and high-energy
      radiation have been on the market since 1988. The TLC-autoradioluminography
      (ARLG) method was developed utilizing such IPs. The conventional TLC method was
      suited for discrimination of microradioactive components; however, the method
      could only present semi-quantitative values. Conversely, the TLC-ARLG method
      showed completely quantitative values. That is, the TLC-ARLG method could be used
      to measure the radioactivity ratio between 14C-radiolabeled spots A and B, which
      were spotted 1 mm apart on a TLC plate, after development with chromatogram, not
      only when the radioactivity ratio between spots A and B was 1:1, but even when it
      was 16:1, within the measurement error of +/- 10%. The ARLG method showed
      sensitivity, resolution, and quantitative reliability far superior to those of
      the scraping-liquid scintillation counter (LSC) method or radiochromatoscanner
      method. In the future, the ARLG method will be widely used as a quantitative
      microanalytical method for unknown radioactive metabolites existing as
      microcomponents in organisms, especially for quantitative analysis considering
      mass balance to dose in biological samples, which is considered to be an
      important point in pharmacokinetic research.

PMID- 7735224
TI  - Relationship between apparent total body clearance of cyclosporin A and its
      erythrocyte-to-plasma distribution ratio in renal transplant patients.
AB  - To establish an optimal method for determining a cyclosporin A (CyA) regimen
      based on physiological changes that occur during immunosuppressive therapy, the
      relationship between apparent CyA body clearance (CL/f) and the CyA erythrocyte
      to-plasma distribution ratio (CyA-EP) was examined using clinical time courses
      obtained during routine monitoring. The CyA-EP, which was calculated by a
      multiple regression formula using routine data, was increased during renal
      dysfunction involving the normal recovery phase after transplantation, during
      nephrotoxicity, during acute tubular necrosis, and during acute renal rejection.
      CyA total body clearance (CLt), calculated by multiplying CL/f and converted
      bioavailability, fc (which is equal to 0.009 x LD, where LD represents the CyA
      level in blood per dose ratio), showed hyperbolic decay with increasing CyA-EP
      (the mean CLt was defined as follows: CLt = 0.937/CyA-EP), whereas fc showed
      exponential decay with increasing CyA-EP (the mean fc was defined as follows: fc
      = 0.593 x exp(-0.155 x CyA-EP)). These findings suggest that total CyA body
      clearance and its bioavailability were suppressed during the renal dysfunction
      phase. Hence, the mean CL/f as a function of the CyA-EP was given by the
      following equation: CL/f = 1.390 x exp(0.204 x CyA-EP)/CyA-EP. Since the CyA-EP
      reflects a patient's disease state and alterations in the CyA pharmacokinetic
      profile, these model formulae should provide an adequate method for determining a
      CyA dosage regimen for several disease states after renal transplantation.

PMID- 7735225
TI  - Angiotensinogen synthesis in the liver is independent of physiological estrogen
      levels.
AB  - We determined the physiological importance of endogenous estrogen in the
      regulation of angiotensinogen synthesis in the liver. The plasma levels of
      angiotensinogen and hepatic levels of angiotensinogen mRNA were studied in the
      rat in comparison to those of T-kininogen, a plasma protein whose synthesis in
      the liver is primarily estrogen-dependent. Plasma levels of T-kininogen and
      hepatic levels of T-kininogen mRNA were 3- and 2-fold higher in adult females,
      respectively, than in adult males, whereas there were no sex differences in
      levels of either plasma angiotensinogen or hepatic angiotensinogen mRNA.
      Ovariectomy in female rats abolished the sex differences in the levels of plasma
      T-kininogen and hepatic T-kininogen mRNA, but it did not affect those of plasma
      angiotensinogen and hepatic angiotensinogen mRNA. These results suggest that, in
      contrast to T-kininogen, angiotensinogen synthesis in the liver is unlikely to be
      controlled by endogenous levels of estrogen.

PMID- 7735226
TI  - Enhancement of LPS triggered TNF-alpha (tumor necrosis factor-alpha) production
      by (1-->3)-beta-D-glucans in mice.
AB  - Effects of (1-->3)-beta-D-glucans on tumor necrosis factor-alpha (TNF-alpha)
      production in mice in vivo were investigated with or without triggering
      stimulation of lipopolysaccharide (LPS). Administration of grifolan (GRN) (100
      250 micrograms/mouse) obtained from Grifola frondosa, did not elevate the TNF
      alpha concentration in serum, but significantly elevated LPS (10
      micrograms/mouse)-elicited TNF-alpha production in serum. The priming effect was
      observed as early as 2 h after administration and remained high for 3 weeks. The
      priming effect was dependent on the strain of mice, i.e. ICR, BALB/c, and MRL/lpr
      (15 weeks old) showed high response. In addition, GRN administration increased
      membrane-bound TNF-alpha assessed by Western blotting and flow cytometry.
      Comparing the activity using structurally related glucans obtained from other
      microorganisms, highly branched glucans, SSG isolated from Sclerotinia
      sclerotiorum IFO 9395 and OL-2 from Omphalia lapidescence significantly increased
      TNF-alpha production. Small molecular weight GRN derivatives prepared by heat
      degradation method showed weaker priming effect. These facts suggested that the
      glucans showed priming effect of TNF-alpha production in vivo and that this
      effect was related to the degree of branching and molecular weight.

PMID- 7735227
TI  - Effects of L-dopa on cholecystokinin octapeptide tissue levels in normal and 6
      hydroxydopamine-treated rat brain.
AB  - We investigated the changes in cholecystokinin octapeptide (CCK8) tissue levels
      after the intraperitoneal administration of L-3,4-dihydroxyphenylalanine (L-dopa)
      in normal and 6-hydroxydopamine (6-OHDA) treated rat brains to clarify the
      interaction between CCK8 and dopamine (DA). The administration of L-DOPA to the
      normal rats elevated the regional CCK8-like immunoreactivity (CCK8LI) tissue
      levels in a dose dependent manner in the frontal cortex, striatum, and nucleus
      accumbens where CCK neurons were closely associated with DA neurons but not in
      the hippocampus where CCK neurons were identified as local circuit neurons.
      Moreover, coadministration of D2-selective antagonist, L-sulpiride, with L-dopa
      inhibited the elevation of CCK8LI levels in several brain regions. This evidence
      indicates that CCK8 release was inhibited by exogenous DA converted from L-dopa
      via D2 receptor stimulation. In the 6-OHDA treated rats on the 3rd day after the
      treatment, the L-dopa administration elevated the CCK8 levels in several regions.
      However, the elevation of CCK8LI levels was not observed on the 7th day after the
      6-OHDA treatment. These results suggest that there would be a great difference in
      the effect of L-DOPA on CCK8LI levels between the 3rd day and 7th day after 6
      OHDA treatment. It was concluded that the changes in CCK8LI levels would be due
      to changes in CCK8 release, and that the CCK8 release would be regulated by
      extracellular DA via D2 receptor.

PMID- 7735228
TI  - Apparent intramolecular acyl migration and hydrolysis of furosemide glucuronide
      in aqueous solution.
AB  - The stability of furosemide glucuronide (FG) was investigated in buffer solutions
      ranging from pH 1 through 10. This glucuronic acid conjugate was the major
      metabolite of furosemide (F) excreted in human urine. FG, obtained by extraction
      from human urine, was purified by ion-exchange chromatography. The concentration
      of FG, acyl migration isomers of FG (FG-iso), and F were determined
      simultaneously with an HPLC method that included fluorescence detection and
      gradient elution. FG was found to be unstable in highly acidic and in neutral to
      alkaline solutions. Hydrogen ion and hydroxy ion catalyzed the hydrolysis of FG
      below pH 2.8 and above pH 5.6, respectively. Above pH 3.7, FG instability led to
      the formation of eight FG-iso compounds. Though beta-glucuronidase cleaved FG,
      the FG-iso compounds were resistant to the enzyme. The half-life of FG in a
      buffer solution at pH 7.4 and 37 degrees C was 4.4 h. The maximum stability of FG
      (half-life about 62 d) occurred at approximately pH 3.2. Below pH 3.7, acyl
      migration products of FG were not detected. Instead, the hydrolysis of FG to F
      and glucuronic acid was followed by the formation of 4-chloro-5
      sulfamoylanthranilic acid (CSA), a secondary product in acidic media.

PMID- 7735230
TI  - Thyroxine binding properties of glycosylated human serum albumin as measured by
      fluorescence.
AB  - Thyroid hormone, thyroxine (T4) binding to glycosylated human serum albumin (G
      HSA), and native human serum albumin (HSA) were studied as a function of pH using
      the fluorescence method. T4 binding affinity for G-HSA was remarkably reduced in
      an alkaline pH as compared with the native HSA. The thermodynamic parameters for
      binding are estimated at pH 7.5: (a) for G-HSA, delta G = -8.50 +/- 0.04 kcal mol
      1 (30 degrees C), delta H = -5.2 kcal mol-1, delta S = +11 e.u.; (b) for HSA,
      delta G = -8.89 +/- 0.04 kcal mol-1 (30 degrees C), delta H = -3.5 kcal mol-1,
      delta S = +18 e.u. These results suggest that the glycosylation of HSA causes a
      variation in the electrostatic interaction between T4 and HSA.

PMID- 7735229
TI  - Effect of oral multiple-dose administration of anti-inflammatory flurbiprofen
      chimera drug on gastric lesion, other toxicities and disposition kinetics.
AB  - Flurbiprofen (FP) was esterified with a histamine H2-antagonist, PPA (N-[3-(3-(1
      piperidinylmethyl)phenoxy)-propyl]-2-(2- hydroxyethylthio)acetamide), to yield a
      chimera drug, FP-PPA, and its protective effect toward gastric lesions, other
      toxicities and the disposition kinetics were investigated, as compared to those
      of FP, in multiple oral administration to rats for 2 weeks. FP-PPA scarcely
      formed any disorder of the gastric mucosa following multiple oral administration.
      The body weight changes and hematological and serum biochemical parameters were
      found to be similar to those in the control group. Some drug metabolizing enzyme
      activities tested were the same as those of the control group. Further, the
      pharmacokinetic parameters were found to be the same after both single and
      multiple oral administration. On the other hand, in the FP treated group, the
      inhibition of body weight increase and changes in serum biochemical and
      hematological parameters were observed due to malabsorption. The absorption rate
      constant was increased significantly after multiple administration as compared to
      that of single administration. It is suggested that these changes in the
      absorption process of FP are due to variations in gastrointestinal permeability
      derived from gastrointestinal damage. The results obtained here indicate clearly
      that the chimera drug FP-PPA scarcely forms any disorder of the gastric mucosa,
      even after multiple oral administration, and is thus a potential candidate for
      oral use.

PMID- 7735231
TI  - The heparin-binding site of human xanthine oxidase.
AB  - The enzyme xanthine oxidase (XOD) has an affinity for heparin and can bind to
      cultured porcine aortic endothelial cells. We have reported that the exposure of
      human XOD (h-XOD) to the lysine-specific reagent trinitrobenzenesulfonic acid or
      the arginine-specific reagent phenylglyoxal caused it to lose its affinity for
      heparin-Sepharose. The heparin-binding sites in h-XOD are further studied in the
      present article. From a chymotryptic digest of cyanogen bromide fragmented h-XOD,
      two peptides with an affinity for heparin-HPLC, A-1 and A-2, were isolated. Amino
      acid sequence analysis showed that both peptides had lysine and/or arginine
      residues. The A-1 region may direct its charged side chains toward the solvent
      while burying its hydrophobic side chains against the hydrophobic inside, because
      the A-1 peptide forms a highly amphipathic structure. Peptide A-2 contains triple
      lysine residues and constitutes a hydrophilic region.

PMID- 7735232
TI  - Caffeine enhances adriamycin antitumor activity in Ehrlich ascites carcinoma
      bearing mice.
AB  - We examined whether caffeine enhances the antitumor activity of adriamycin (ADR),
      in terms of prolonging survival in Ehrlich ascites carcinoma(ascites-type)
      bearing mice. After administration of ADR at a dose of 0.5 mg/kg/d for 5d
      together with caffeine (100 mg/kg/d x 5 d), the survival period was increased by
      39%. However, caffeine had little effect on this ADR induced-prolongation of
      survival following administration of ADR at 2.0 mg/kg/d for 4 d. Although a
      significant increase in ADR concentration in the ascites tumor was seen after
      administration of ADR at a dose of 0.5 mg/kg, caffeine failed to increase ADR
      concentration in the ascites tumor after administration of ADR at a dose of 2.0
      mg/kg. The effect of caffeine thus appears to be due to its effect on the tumor
      distribution of ADR.

PMID- 7735234
TI  - Effects of steroidal glycosides on blood glucose in normal and diabetic mice.
AB  - Two steroidal glycosides, PO-1 and PO-2, were tested as a new hypoglycemic drug.
      PO-2 showed remarkable hypoglycemic activity on i.p. injection into normal mice.
      PO-1 slightly lowered the blood glucose in normal mice. Furthermore, PO-1 and PO
      2 exhibited significant hypoglycemic effects in streptozotocin-induced diabetic
      mice. However, a steroid, diosgenin, did not affect the blood glucose level in
      either normal or streptozocin-induced diabetic mice, indicating that the
      branching glucose units are essential for the biological activity.

PMID- 7735233
TI  - Active-oxygen scavenging activity of plant extracts.
AB  - To find antioxidative compounds present in plants, 65 types of plant extract were
      tested using the neotetrazolium method for evidence of superoxide anion
      scavenging effects and 7 plant extracts were selected for further investigation.
      The activity of active-oxygen scavengers such as superoxide anion radicals,
      hydroxyl radicals, singlet oxygens and lipid peroxides in the 7 plant extracts
      (Aeseclus hippocastanum L., Hamamelis virginiana L. Polygonum cuspidatum Sieb.,
      Quercus robur L., Rosemarinous officinalis L., Salvia officinalis L. and
      Sanguisorba officinalis L.) was examined in detail by both ESR spin-trapping and
      malondialdehyde generation. Furthermore, the active-oxygen scavenging activity of
      these plant extracts was evaluated using a murine dermal fibroblast culture
      system. Both Aeseclus hippocastanum L. and Hamamelis virginia L. were found to
      have strong active-oxygen scavenging activity of and protective activity against
      cell damage induced by active oxygen. Both Aeseclus hippocastanum L. and
      Hamamelis virginiana L. are proposed as potent plant extracts with potential
      application as anti-aging or anti-wrinkle material for the skin.

PMID- 7735235
TI  - Effect of ophthalmic preservatives on serum concentration and local irritation of
      ocularly applied insulin.
AB  - We previously compared hypoglycemic responses after the instillation of insulin
      formulations. A hypoglycemic response was actually observed after an instillation
      of insulin with ophthalmic preservatives. In the present study, in order to
      evaluate the usefulness of insulin formulation containing ophthalmic
      preservatives, a serum concentration of insulin and an irritation to the eye were
      investigated after instillation of the insulin formulation in albino rabbits. The
      ophthalmic preservatives used were benzalkonium chloride, paraben, 2
      phenylethanol, benzyl alcohol and sorbic acid. As a result, ophthalmic
      preservatives, especially benzalkonium chloride and paraben, increased the serum
      concentration of insulin. The insulin concentration showed a significant
      correlation with the hypoglycemic response reported previously. This result
      indicates that ophthalmic preservatives increase the absorption of ocularly
      applied insulin, and the absorbed insulin decreases serum glucose concentration.
      The insulin formulation with preservatives showed little irritation on rabbit
      eyes according to blinking measurements. These results indicate that ophthalmic
      preservatives are useful for the systemic delivery of ocularly applied insulin.

PMID- 7735236
TI  - Inhibition of 5'-deoxy-5-fluorouridine phosphorolysis by
      acyclopyrimidinenucleosides in intestinal tissue homogenates.
AB  - This study examined the inhibitory effect of acyclopyrimidinenucleosides on 5'
      deoxy-5-fluorouridine (5'-DFUR) phosphorolysis in intestinal tissue derived from
      rabbit, rat, mouse, and human. 5-Bromoacyclouridine, 5-fluoroacyclouridine,
      acyclouridine, and 5-nitroacyclouridine showed little or only moderate effect,
      but acyclothymidine [5-methyl-1-(2'-hydroxyethoxymethyl)uracil] showed strong
      inhibitory effect on 5'-DFUR phosphorolysis in intestinal tissue homogenates
      derived from human. In the absence of inhibitor (acyclothymidine), the Vmax of 5'
      DFUR phosphorolysis was 2.66 mumol/min and the Km was 0.57 mM in human intestinal
      homogenates. The Vmax was unaltered by increased inhibitor concentration. The
      maximal inhibitory effect of acyclothymidine on 5'-DFUR phosphorolysis in rat
      homogenates was over 90%. The Ki/Km was 0.63 in human, 2.14 in rabbit, 1.09 x 10(
      2) in rat, and 1.71 x 10(-2) in mouse. These data show that acyclothymidine is a
      competitive inhibitor of 5'-DFUR phosphorolysis, and that it can inhibit not only
      uridine phosphorylase but also thymidine phosphorylase.

PMID- 7735237
TI  - Transdermal delivery of theophylline using an ethanol/panasate 800-ethylcellulose
      gel preparation.
AB  - A novel ethylcellulose gel preparation using an ethanol/panasate 800
      (tricaprylin) (40/60) binary lipophilic vehicle was developed and applied to the
      transdermal delivery of theophylline. The in vitro skin permeability of
      theophylline across excised hairless mouse skin was improved by the use of this
      ethanol/panasate 800 (40/60) binary vehicle compared with either ethanol or
      panasate 800 as a single vehicle, and the addition of lauric acid as a permeation
      enhancer to the binary vehicle shortened the lag time and increased the permeated
      amount of theophylline up to 6 h (initial permeation amount). The in vitro
      permeability of theophylline from the ethanol/panasate 800 (40/60)-ethylcellulose
      gels decreased with an increase in the content of ethylcellulose in the gels. In
      the in vivo evaluation using abdominal rat skin, the ethanol/panasate 800 (40/60)
      7% (w/w) ethylcellulose gel produced a good feature as a sustained-release
      preparation, with a relatively high bioavailability (BA) of theophylline, and
      dose dependency was observed.

PMID- 7735238
TI  - Possible involvement of different mechanisms in sudden death induced by
      endothelin-1 and big endothelin-1.
AB  - The effects of diltiazem and phosphoramidon on sudden death induced by endothelin
      (ET)-1 and by big ET-1 were compared in rodents. Diltiazem (2 mg/kg, i.v.)
      remarkably diminished the lethal toxicity of ET-1 with a reduction in the extent
      of the rise in plasma immunoreactive ET-1-like activity (IR-ET-1), tissue IR-ET-1
      accumulation in the heart and the rise in plasma potassium concentration. In big
      ET-1-induced lethality, diltiazem only slightly prolonged the latency and did not
      reduce the mortality. Although diltiazem moderately inhibited the rise in plasma
      IR-ET-1 and potassium concentration in these mice, it did not affect the
      accumulation of IR-ET-1 in the heart, lung or kidney. Phosphoramidon (2 mg/kg,
      i.v.) decreased the lethality of big ET-1 with the decrement in elevation of IR
      ET-1 in the heart, lung and plasma as well as with the decrease in plasma
      potassium concentration, but it failed to improve any parameters in ET-1-induced
      lethality. In anesthetized rats, ET-1 (5 nmol/kg, i.v.) elevated ST-segment of
      electromyocardiograms, and diltiazem (2 mg/kg, i.v.) significantly reversed this
      change. Big ET-1 (25 nmol/kg, i.v.) also induced the ST-segment elevation, which
      was significantly inhibited by phosphoramidon but not by diltiazem. These
      findings suggest that accumulation of ET-1 in the heart, which may lead to lethal
      cardiac ischemia, is an important factor in the lethality of ET-1, while
      additional factors (such as hemoconcentration and bronchoconstriction) may be
      involved in big ET-1-induced lethality.

PMID- 7735239
TI  - Therapeutic efficacy of 5-fluorouracil prodrugs using endogenous serum proteins
      as drug carriers: a new strategy in drug delivery system.
AB  - To establish a novel drug delivery system for 5-fluorouracil (5FU), we have
      developed a system in which the low-molecular-weight prodrugs of 5FU bound to
      endogenous serum proteins, thus circulating like those proteins. Subsequently,
      the prodrugs were slowly hydrolyzed to generate active 5FU in the bloodstream. To
      examine the therapeutic effect of these prodrugs, we injected them into BALB/c
      mice previously implanted subcutaneously with Meth A sarcoma. Among the prodrugs,
      1-(N-4-chlorophenyl-N-methylcarbamoyl)-5-fluorouracil (5FU-1pCPMC) was effective
      in reducing tumors and prolonging survival time. The non-hydrolyzable compound, 1
      (4-chlorobenzyl)-5-fluorouracil, did not show any therapeutic effect, suggesting
      that the therapeutic efficacy of 5FU-1pCPMC is due to the sustained release of
      5FU from the serum protein-prodrug complex. The data shown here may create a new
      field in drug delivery system technology.

PMID- 7735240
TI  - Comparison of the blood clearance of triple- and single-helical schizophyllan in
      mice.
AB  - (1-->3)-beta-D-Glucans exhibit a variety of biological and immunopharmacological
      activities, and the degree of these activities depends on the nature of the
      individual glucans e.q. molecular weight, degree of branching and conformation.
      Based on the generally accepted evidence that the conformation of Sonifilan (SPG)
      used clinically is a triple helix, we prepared alkali-denatured SPG (SPG-OH) as a
      single helix conformer. In this report, we measured the concentration of beta
      glucan administered to mice by using a beta-glucan-specific reagent prepared from
      limulus amebocyte lysate (Gluspecy [G test], Seikagaku Corporation, Tokyo) and
      discuss the blood clearance of SPG and SPG-OH following intraperitoneal (i.p.) or
      intravenous (i.v.) administration. Comparing the clearance of SPG-OH from the
      blood with that of SPG, SPG-OH was removed faster than SPG following both i.p.
      and i.v. administration. This strongly suggests that the clearance of beta
      glucans is dependent on their conformation.

PMID- 7735241
TI  - Absorption of (-)-epigallocatechin gallate into rat portal vein.
AB  - Following oral administration of (-)-epigallocatechin gallate to rats, the
      presence of (-)-epigallocatechin gallate was examined in the portal blood. A
      compound present in the blood was identified as (-)-epigallocatechin gallate by
      HPLC and mass spectrometry analysis. The results clearly demonstrate that (-)
      epigallocatechin gallate is absorbed, at least in part, into rat portal blood.

PMID- 7735242
TI  - A new statistical procedure of interval hypothesis testing for bioequivalence
      studies.
AB  - A simplified procedure of interval hypothesis testing was investigated and
      established for bioequivalence studies. The characteristics of this procedure
      were compared with those of other statistical procedures.

PMID- 7735243
TI  - Molecular cloning of cDNA encoding rat 2,3-oxidosqualene: lanosterol cyclase.
AB  - A cDNA encoding rat 2,3-oxidosqualene: lanosterol cyclase, the enzyme responsible
      for the complex cyclization/rearrangement step in sterol biosynthesis, was cloned
      by extensive application of PCRs. Oligonucleotide primers were designed in sense
      and anti-sense directions corresponding to internal peptide sequences of purified
      enzyme. Successive PCRs with all possible combinations of these primers yielded a
      178-bp fragment, and based on its sequence full nucleotide sequence of cDNA was
      obtained by a "rapid amplification of cDNA ends" (RACE) method.

PMID- 7735244
TI  - Enhancing effects of diphenyl dimethyl dicarboxylate on serum antibody production
      in BALB/c mice.
AB  - The effects of diphenyl dimethyl dicarboxylate (PMC) on serum antibody production
      were investigated in BALB/c mice. PMC (3 and 6 mg/kg/d, respectively) was orally
      administered to the mice for 14 consecutive days. The effects on antibody
      production were assessed by enzyme-linked immunosorbant assay (ELISA) of
      immunoglobulin (Ig) subset levels in serum, collected at week 2 from mice with or
      without immunization by an i.p. injection of 0.1 mg ovalbumin (OVA) in complete
      Freund's adjuvant (CFA) at week 1 after the first oral administration of PMC. PMC
      showed a significant enhancement of the levels of total serum IgG, IgG1, IgG2a
      and IgA without the immunization, while total IgE levels were not affected. When
      mice were immunized with OVA after the oral administration of PMC, moreover, a
      marked stimulation of antibody production was observed in mice fed 6 mg/kg/d PMC,
      hardly accompanied with increase of IgE levels. In these mice, additionally, PMC
      significantly elevated anti-OVA IgG (including both IgG1 and IgG2a mediated by
      different T-helper cells) levels. These findings indicate that PMC enhances
      antibody production in mice with therapeutic concentrations that have shown great
      promise in the treatment of chronic hepatitis virus of type B.

PMID- 7735245
TI  - Hypocholesterolemic effect of 5 beta-cholane-3 alpha,7 beta,24-triol-24- sulfate
      in hamsters.
AB  - We studied the effect of 5 beta-cholane-3 alpha,7 beta,24-triol-24-sulfate (UDC-O
      sulfate) on ileal active transport of cholyltaurine, on hepatic cholesterol 7
      alpha-hydroxylase activity, on serum and liver cholesterol levels, on intestinal
      absorption of cholesterol, and on bile salt composition of gallbladder bile in
      hamsters. Experiments using the everted gut sacs show that UDC-O-sulfate inhibits
      the ileal active transport of cholyltaurine. In experiments feeding the diets
      with either UDC-O-sulfate, cholesterol, or both to hamsters, the addition of UDC
      O-sulfate to the cholesterol-enriched diet reduced the elevation of serum and
      liver cholesterol levels caused by cholesterol feeding. Supplementation with UDC
      O-sulfate to the standard diet was likely to reduce serum and liver cholesterol
      levels. Cholesterol 7 alpha-hydroxylase activity was higher in the two UDC-O
      sulfate supplemented groups than in the two corresponding groups, the standard
      diet group and the cholesterol enriched diet group, respectively. Addition of UDC
      O-sulfate to the standard and cholesterol diets did not change intestinal
      absorption of cholesterol. The change of the bile salt composition in hamsters
      fed UDC-O-sulfate may also suggest that the bile alcohol sulfate inhibits the
      intestinal absorption of endogenous bile salts. Hence the hypocholesterolemic
      activity of dietary UDC-O-sulfate is thought to be the effect of the partial
      interruption of the enterohepatic circulation of endogenous bile salts.

PMID- 7735246
TI  - Effects of alkaloids extracted from the stem bark of Hunteria zeylanica on acute
      inflammation in experimental animals.
AB  - The effects of crude alkaloids extracted from the stem bark of Hunteria zeylanica
      GARD. (H. zeylanica) on acute inflammatory responses such as carrageenin-induced
      paw edema in rats and croton oil- and arachidonic acid-induced ear edema in mice
      were investigated. Oral administration of H. zeylanica alkaloid extract (200-400
      mg/kg) significantly suppressed the paw swelling induced by carrageenin. In the
      croton oil-induced ear edema, topically applied H. zeylanica alkaloid extract, at
      doses of 200 and 400 mg/ml, also significantly reduced ear edema. Moreover, the
      extract (50-200 mg/kg, p.o.) reduced in a dose-dependent manner the ear swelling
      induced by topically applied arachidonic acid (2 mg/ear). These results suggest
      that the inhibitory effects of H. zeylanica alkaloid extract on acute edema
      formation are partly due to inhibition of 5-lipoxygenase and cyclooxygenase
      activity.

PMID- 7735247
TI  - Increase in respiratory resistance after exercise in conscious guinea pigs. As a
      model for exercise-induced asthma.
AB  - We have developed an experimental model for exercise-induced asthma (EIA) using
      conscious guinea pigs. Respiratory resistance (Rrs) was measured before and after
      exercise (running). When a 0.05% lipopolysaccharide (LPS) was inhaled by guinea
      pigs which had been pretreated with a corticosteroid biosynthesis inhibitor
      metyrapone (50 mg/kg, i.v.), Rrs significantly increased 24 h after exercise.
      Metyrapone had no effect, however, on the LPS-induced increase in the numbers of
      macrophages, eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage
      fluid (BALF). In order to examine the role of airway inflammation, the effects of
      murine recombinant interleukin-5 (mrIL-5) and platelet activating factor (PAF)
      were investigated in guinea pigs. The exercise-elicited increase in Rrs was
      observed 24 h later than the treatment with mrIL-5 in metyrapone-treated animals.
      The number of macrophages, eosinophils and neutrophils increased in the BALF of
      mrIL-5-treated animals. In contrast, a 0.05% PAF aerosol caused an increased
      number of eosinophils in BALF, but did not affect Rrs after exercise in either
      metyrapone-treated or non-treated animals. Moreover, to evaluate the value of
      this model as a pharmacological tool, the effect of ketotifen and prednisolone on
      the exercise-induced increase in Rrs was investigated. Prior administration of
      ketotifen and prednisolone showed a tendency to prevent, or clearly inhibited,
      the exercise-induced increase in Rrs in animals treated with the combination with
      LPS and metopyrone.

PMID- 7735248
TI  - DNA-strand breaks induced by dimethylarsinic acid, a metabolite of inorganic
      arsenics, are strongly enhanced by superoxide anion radicals.
AB  - We previously reported that dimethylarsinic acid (DMAA), a major metabolite of
      inorganic arsenics, induced DNA single-strand breaks (ssb) both in vivo and in
      cultured alveolar type II (L-132) cells in vitro, possibly via the production of
      dimethylarsenic peroxyl radicals. Here, the interaction of superoxide anion
      radicals (O2-) in the induction of ssb in L-132 cells was investigated using
      paraquat, an O2(-)-producing agent. A significant enhancement of ssb formation
      was observed in the DMAA-exposed cells when coexposed to paraquat. This
      enhancement occurred even when post-exposed to DMAA after washing, suggesting
      that the DMAA exposure caused some modification of DNA such as DNA-adducts, which
      was recognized by active oxygens to form ssb. An experiment with UV-irradiation,
      which was likely to induce ssb at the modified region, supported the possibility
      of DNA modification by DMAA exposure. An ESR study indicated that O2- produced by
      paraquat in DMAA-exposed cells was more consumed than in non-exposed cells,
      assumingly through the reaction with the dimethylarsenic-modified region of DNA.
      The species of active oxygens were estimated by using diethyldithiocarbamate,
      aminotriazole, diethylmaleate, hydrogen peroxide (H2O2), gamma-irradiation and
      ethanol. O2- but neither H2O2 nor hydroxyl radicals was very likely to contribute
      to the ssb-enhancing action of paraquat.

PMID- 7735249
TI  - Activation of N-nitrosodialkylamines to mutagens by a metalloporphyrin/oxidant
      model system for cytochrome P450.
AB  - N-Nitrosodialkylamines are environmental alkylating carcinogens which are
      metabolically activated to alpha-hydroxy nitrosamines by cytochrome P450. The
      precise mechanism of their activation is not well understood, and a simplified
      chemical model for cytochrome P450 as a non-enzymatic system is useful for
      investigating the mechanism. In the present study, a chemical model was used in a
      bacterial mutation assay as a substitute of S9 mix, and its ability in the
      activation of N-nitrosodialkylamines was elucidated. In the presence of
      tetrakis(pentafluorophenyl)porphyrinatoiron(III) chloride and tert-butyl
      hydroperoxide, the mutagenicity of N-nitrosodialkylamines [alkyl = methyl (NDM),
      ethyl (NDE), propyl (NDP) and butyl (NDB)] in Salmonella typhimurium YG7108 was
      detected. The mutagenicity increased by the pre-incubation and was dependent on
      the concentration of mutagens. The mutagenic activity of N-nitrosodialkylamines
      in Salmonella typhimurium YG7108 was in the following order: NDB > NDM > NDE
      approximately NDP. The formation of aldehydes derived from dealkylation in the
      present model was exemplified by the formation of acetaldehyde from NDE. These
      results showed that N-nitrosodialkylamines were activated by the model system,
      and consequent mutagenicity was observed. The oxidation by the model can mimic
      the metabolic activation of chemical carcinogens by cytochrome P450, and the
      biomimetic catalyst is useful in investigating the mechanisms of the metabolic
      pathway of N-nitrosodialkylamines.

PMID- 7735250
TI  - Improvement of fusing ability of human sperm to zona-free hamster eggs by
      conditioned media.
AB  - A conditioned medium (CM) was prepared by culturing human sperm at 3.0 x 10(6)
      sperm/ml for 12 h. The fusion index increased significantly when the sperm
      penetration assay (SPA) was performed with CM (0.6 without CM to 2.0 with CM).
      The conditioned medium was also effective on the sperm from 11 patients who
      showed a low or zero value in SPA and who's in vitro fertilization treatment
      failed. When CM from the sperm of healthy donors was added to these patients'
      sperm, the fusing ability to zona free hamster eggs was significantly restored.

PMID- 7735251
TI  - Improvement of cisplatin toxicity and lethality by juzen-taiho-to in mice.
AB  - The effects of oral treatment with 1-, 5-, 10- and 20-fold the usual daily dose
      of Juzen-taiho-to on the nephrotoxicity, immunosuppression, hepatic toxicity and
      gastrointestinal toxicity caused by i.p. administration of 3.0 mg/kg cisplatin
      (CDDP) 9 times (on days 3, 4, 5, 6, 7, 8, 10, 11, and 12) were examined in ddY
      mice inoculated with sarcoma 180 (S-180) cells on day 1. The increase in blood
      urea nitrogen, serum creatinine, serum glutamic-oxaloacetic transaminase, serum
      glutamic-pyruvic transaminases and relative stomach weight and decrease in white
      blood cell count, platelet count, relative spleen and thymus weight, food intake
      and body weight caused by CDDP were inhibited to nearly the control levels
      without reducing the antitumor activity of CDDP against S-180 by the oral
      treatment with either 10-fold (1.7 g/kg) or 20-fold (3.4 g/kg) the usual daily
      dose of Juzen-taiho-to 12 times (on days 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14,
      and 15). All the mice receiving 4.5, 6.0, 7.5, 9.0, and 12.0 mg/kg CDDP died by
      day 12, while treatment with 3.4 g/kg Juzen-taiho-to efficiently prolonged the
      survival time. These findings indicate that Juzen-taiho-to may provide protection
      against most clinical toxicity caused by CDDP, and Juzen-taiho-to may allow us to
      administer a much higher dose of CDDP in clinical therapy.

PMID- 7735252
TI  - Protective activity of hamamelitannin on cell damage induced by superoxide anion
      radicals in murine dermal fibroblasts.
AB  - Previously we demonstrated that hamamelitannin (2',5-di-O-galloyl hamamelose) in
      Hamamelis virginiana L. exhibits potent superoxide-anion scavenging activity. We
      then examined the physiological and pharmacological activities of hamamelitannin
      as well as its functional homologues, gallic acid and syringic acid. The
      following results were obtained: (1) Hamamelitannin has a higher protective
      activity against cell damages induced by superoxide anions than gallic acid which
      is the functional moiety of hamamelitannin. The protective activity of
      hamamelitannin on murine fibroblast-damage induced by superoxide anions was found
      at a minimum concentration of 50 microM, while the corresponding figure for
      gallic acid was 100 microM. (2) Pre-treatment of fibroblasts with hamamelitannin
      enhances cell survival. (3) The superoxide-anion scavenging activity of the
      compound in terms of its IC50 value (50% inhibition concentration of superoxide
      anion radicals generated) was evaluated by ESR spin-trapping. Both hamamelitannin
      (IC50 = 1.31 +/- 0.06 microM) and gallic acid (IC50 = 1.01 +/- 0.03 microM)
      exhibited high superoxide-anion scavenging activity followed by syringic acid
      (IC50 = 13.90 +/- 2.38 microM). (4) When hamamelitannin was treated with
      superoxide anions generated by a KO2-crown ether system, HPLC analysis showed the
      disappearance of hamamelitannin and the concomitant formation of hamamelitannin
      derived radicals (g = 2.005, delta H1 = 2.16 G, delta H2 = 4.69 G) was detected
      by ESR spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735253
TI  - A saturable tissue-angiotensin I converting enzyme (ACE) binding model for the
      pharmacokinetic analysis of imidapril, a new ACE inhibitor, and its active
      metabolite in human.
AB  - In order to obtain a rational explanation and analytical method of the unique
      pharmacokinetic behaviors of imidapril and imidaprilat in human, a new
      pharmacokinetic model was designed by introducing a saturable-reversible
      angiotensin I converting enzyme (ACE)-imidaprilat binding process and a linear
      imidapril-imidaprilat conversion process. According to the new model, six
      differential equations were given which considered the mass balance of both
      compounds in each component. Various pharmacokinetic parameters were estimated by
      the simultaneous curve fitting method using the plasma concentration data and the
      urinary excretion data of imidapril and imidaprilat in a multiple dosing study of
      healthy human volunteers. To validate the value of each parameter, this
      pharmacokinetic model was also applied to analyze the various plasma
      concentration data of both compounds in the single dosing studies with four
      different dosages, 2.5,5, 10, and 20 mg. Excellent curve fitting was obtained in
      every case, suggesting that the proposed pharmacokinetic model is applicable for
      predicting the plasma concentrations of imidapril and imidaprilat under various
      dosage conditions of clinical use.

PMID- 7735254
TI  - The relationship between the pharmacological effect of amitriptyline based on an
      improved forced-swimming test and plasma concentration in rats.
AB  - The relationship between the plasma concentration of amitriptyline (AMI) and its
      pharmacological effect was investigated in rats. The plasma concentration of AMI
      was maintained constantly from 5 h to 7 d after intraperitoneal infusion by the
      implantation of an osmotic minipump with an adjusted release rate of 20 mg/kg/d
      of AMI. Neither the plasma or brain concentrations of AMI in a 24-h infusion
      group were significantly different as compared with those in the 7-d group. The
      pharmacological effect of AMI was measured by our improved forced-swimming test.
      When AMI (dose of 20 and 50 mg/kg/d) was infused, the pharmacological effect in
      both infusion groups of rats was increased significantly at each dose in
      comparison to that of the control rats (p < 0.05). With 10 mg/kg/d infusion, the
      effect in the 7-d group increased significantly as compared with that of the
      control (p < 0.05), although the effect in the 24-h group did not change. The
      effect was increased in both groups with an increase of dose. When the effect was
      plotted to the area under the plasma concentration-time curve (AUC), the effect
      approached a limiting value (12 micrograms/ml.h). Therefore, it was suggested
      that 12 micrograms.ml/h as the AUC for AMI was enough to obtain a maximum AMI
      pharmacological effect in rats. From these results, we concluded that the AUC for
      AMI may be a useful index to evaluate its pharmacological effect, rather than the
      plasma concentration.

PMID- 7735255
TI  - Inhibition kinetics of theophylline metabolism by mexiletine and its metabolites.
AB  - To further characterize the mode of drug interaction between theophylline (TP)
      and mexiletine (ME), in vitro kinetic studies were carried out using rat liver
      microsomes and 9000 x g supernatant. The kinetic study revealed that the Km value
      and Vmax/Km ratio for the metabolic conversion of TP to 1,3-dimethyluric acid
      (1,3-DMU) were the second lowest and the highest, respectively, of four metabolic
      pathways. Thus, the rank of efficiency of the oxidative metabolism by microsomal
      cytochrome P-450 (P-450) isozymes was TP to 1,3-DMU > TP to 1-methylxanthine (1
      MX) > TP to 3-MX > 1,3-DMU to 1-methyluric acid, suggesting that the isozyme
      metabolizing TP would have a higher affinity for the oxidation at the 8-position
      in TP molecules than at the 1- and 3-positions. Lineweaver-Burk plots showed that
      the conversion of TP to 3-MX and to 1,3-DMU was inhibited competitively by ME and
      its metabolites, and that the pathway of TP to 1-MX was inhibited
      noncompetitively. In consideration of the Ki values calculated, it seems probable
      that deamino-p-hydroxy ME (DApHME) might be the most potent inhibitor of the
      metabolic pathways of TP, and that the rank order of inhibition is approximately
      DApHME > p-hydroxy ME > deamino-hydroxymethyl ME > ME > hydroxymethyl ME, with
      some exceptions. The mechanism of the interaction between TP and ME is probably
      due to the metabolic antagonism in the liver, and TP, ME and their metabolites
      share some of the same metabolic pathways, mediated by P-450 isozymes.

PMID- 7735256
TI  - Relationship between the anchor structure of the galactosyl ligand for liposome
      modification and accumulation in the liver.
AB  - Liposomes which have been modified with (8-hexadecanoylamido-3,6-dioxaoctyl)-beta
      D-galactose (Gal-t-pa), a straight chain palmitoyl derivative, and are composed
      of dipalmitoylphosphatidylcholine (DPPC), cholesterol (CH), and dicetyl phosphate
      (DCP) at a ratio of 10:10:1, showed the same accumulation in the liver as the
      control liposome. Also, liposomes which have been modified with [8-(2
      hexadecyloctadecanoylamido)-3,6-dioxaoctyl]-beta-D-gal actoside (Gal-t-psa)
      showed remarkable accumulation in the liver. The accumulation of liposomes
      modified with galactose derivatives in the rat liver differed markedly according
      to the anchor structure. To clarify the cause of this finding, we produced
      [3H]inulin entrapped [14C]Gal-t-pa modified double label liposomes and evaluated
      changes in their rat plasma concentration, distribution in the organs, and the in
      vitro interaction with rat plasma. [14C]Gal-t-pa on the liposome surface bound to
      serum albumin and was released, resulting in no accumulation in the liver. In
      addition, sialic acid palmitoyl derivatives and glucuronic acid palmitoyl
      derivatives behaved similarly. As with the galactose derivatives, they also bound
      to serum albumin, being released from liposomes. These results suggest that
      adequate attention should be paid to the anchor structure of the ligand, in order
      to incorporate a recognition element into liposomes for transport to cells.

PMID- 7735257
TI  - Studies on the quantitative autoradiography. I. Radioluminography for
      quantitative autoradiography of 14C.
AB  - Evidence is presented to elucidate whether or not quantitative analysis of
      autoradiographs can be obtained with a 14C-labelled compound by the use of a new
      type of radiosensor called Imaging plate (IP). Our results showed that a linear
      relationship between relative intensity of PSL-BG and radioactivity of a given
      area was obtained. The linearity was maintained in a relatively wide range from
      10(1) to 10(5) dpm of radioactivity. About 100 times higher sensitivity of the IP
      than any commercially available X-ray film was demonstrated for not only 14C
      radioactive standard sources but also experimentally obtained 14C-radioactive
      spots developed on a TLC plate. Results also showed a linear relationship between
      relative intensity and radioactivity of the specimens in a very wide range from
      10(1) to 10(5) dpm/mg after exposure for 7d. Furthermore, the relationship
      between PSL-BG and relative exposure (radioactivity x exposure time) was linear
      when PSL-BG was from 10(1) to 10(5). In addition to the above properties, a
      combination of IP and BAS2000, a computerized image display system, was able to
      completely erase the background prior to use.

PMID- 7735258
TI  - Kinetic studies of the inhibition of a human liver 3 alpha
      hydroxysteroid/dihydrodiol dehydrogenase isozyme by bile acids and anti
      inflammatory drugs.
AB  - We have investigated the steady-state kinetics for a cytosolic 3 alpha
      hydroxysteroid/dihydrodiol dehydrogenase isozyme of human liver and its
      inhibition by several bile acids and anti-inflammatory drugs such as
      indomethacin, flufemanic acid and naproxen. Initial velocity and product
      inhibition studies performed in the NADP(+)-linked (S)-1-indanol oxidation at pH
      7.4 were consistent with a sequential ordered mechanism in which NADP+ binds
      first and leaves last. The bile acids and drugs, competitive inhibitors with
      respect to the alcohol substrate, exhibited uncompetitive inhibition with respect
      to the coenzyme, with Ki values less than 1 microM, whereas indomethacin
      exhibited noncompetitive inhibition (Ki < 24 microM). The kinetics of the
      inhibition by a mixture of the two inhibitors suggests that bile acids and drugs,
      except indomethacin, bind to overlapping sites at the active center of the enzyme
      coenzyme binary complex.

PMID- 7735259
TI  - Studies on the quantitative autoradiography. II. Radioluminography for
      quantitative autoradiography of 3H.
AB  - The process of obtaining 3H-autoradiographic (ARG) images has been expected for a
      long time. A few X-ray films with no protection layer are commercially available,
      however, they do not give a reliable image which can be quantitated and can give
      good contrast. We tried to fabricate a 3H-type sensor which has no protection
      layer on a highly sensitive sensor, and called it Imaging plate (IP). The IP is
      composed of one of the specially designed photo-stimulable phosphors containing
      of BaFX: Eu2+(X = Cl, Br or I) crystals. Results indicated a good contrast and
      reliable whole-body ARG image of 3H-labelled glucose with trial IP, which has
      never been obtained with any X-ray films even if these were subjected to a long
      exposure time. The ARG image can be displayed by either black-and-white hard copy
      or a colored one with the digital display representing relative intensity of
      photostimulated luminescence (PSL) without back ground (BG) or relative intensity
      concentration ((PSL-BG)/S), where S was equivalent to 100 pixels (1 mm2).
      Similarly to the experimental results of 14C, the linear relationship relative
      intensity and radioactivity of the 3H standard sources was demonstrated with a
      very wide range of 10(2) to 10(5) dpm/mg upon the exposure for 7d. Also the
      relationship between relative intensity and relative exposure (radioactivity x
      exposure time) was linear within the latitude of relative intensity 10(1) to
      10(5) (PSL-BG). The trial IP was particularly effective for the quantitative
      autoradiography of TLC plates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735260
TI  - Mechanisms of baroreceptor activation.
AB  - The determinants of the nerve activity generated at the baroreceptor endings have
      been examined. 1) In the isolated carotid sinus, the placement of activated
      bovine aortic endothelial cells decreased baroreceptor activity (BRA) in a
      reversible manner. Both endothelin and nitric oxide (NO) suppress BRA, whereas
      prostacyclin (PGI2) increases activity. 2) The BRA in single units declines and
      often ceases during non-pulsatile increases in carotid sinus pressure sustained
      over several minutes. This "adaptation" is attenuated by the transient potassium
      channel (IA) blocker 4-aminopyridine (4-AP) and not by inhibition of the Na+/K+
      pump. 3) In preliminary studies, mechano-electrical transduction was examined in
      isolated and cultured nodose ganglion neurons. Opening of stretch-activated (SA)
      channels by suction on the cell-attached patch was seen infrequently; however,
      probing the neurons consistently increased their intracellular calcium [Ca++]i
      measured with fura-2. This increase in [Ca++]i is blocked by gadolinium (Gd3+), a
      trivalent lanthanide reported to block SA channels. Gd3+ also blocks the BRA in
      the carotid sinus. We conclude that paracrine factors significantly modulate BR
      sensitivity, that selective ionic mechanisms (the 4-AP sensitive K+ channels)
      determine the degree of "adaptation" of BR to elevated pressure, and that SA
      channels sensitive to Gd3+ may be the mechano-electrical transducers in BR
      neurons.

PMID- 7735261
TI  - Neurotransmitters and neuropeptides in the baroreceptor reflex arc: connections
      between the nucleus of the solitary tract and the ventrolateral medulla oblongata
      in the rat.
AB  - The primary baroreceptor area (nucleus of the solitary tract-NTS) is anatomically
      interconnected with the rostral ("vasomotor area") and the caudal ("vasodepressor
      area") ventrolateral medulla by a well-defined arc of neuronal pathways. The
      chemical character and the direction of these pathways have been investigated
      with immunohistochemical and neurochemical techniques in intact and brainstem
      operated rats. The transection of the neuronal arc resulted in an accumulation of
      tyrosine hydroxylase immunoreactivity in a small group of cells in the NTS
      adjacent to the area postrema, ipsilateral to the knife cut. Decreased
      angiotensinogen mRNA and atrial natriuretic peptide concentrations were measured
      in the ventrolateral medulla after the cut, and an accumulation of angiotensin II
      immunoreactivity was found in neuronal perikarya in the ipsilateral NTS.
      Intracranial vagotomy caused marked depletions in glutamate levels in the
      subcommissural portion of the NTS and in the caudal ventrolateral medulla but
      nowhere else in the brainstem investigated including the rostral ventrolateral
      medulla.

PMID- 7735262
TI  - Cardiovascular responses to agmatine, a clonidine-displacing substance, in
      anesthetized rat.
AB  - We investigated the cardiovascular responses in anesthetized ventilated rats to
      agmatine (decarboxylated arginine), an amine which is an endogenous clonidine
      displacing substance (CDS) synthesized in brain. Intracisternal agmatine dose
      dependently increased sympathetic nerve activity and arterial pressure (at 400
      nmol by 8.7 +/- 2.1 microV and 28.6 +/- 2.7 mmHg, respectively) and blocked
      arterial baroreflex reflexes. Microinjection of agmatine into the rostral
      ventrolateral medulla (RVL) had no effect on arterial pressure or sympathetic
      nerve activity while iontophoresis of agmatine onto defined vasomotor neurons of
      RVL was also without effect. Agmatine (i.v.) decreased sympathetic nerve activity
      and arterial pressure probably by blocking the transmission through sympathetic
      ganglia and by direct dilation of vascular smooth muscles. Despite binding like
      clonidine to alpha 2-adrenergic receptors and imidazoline (I)-receptors of both
      classes, agmatine does not replicate the central or peripheral actions of
      clonidine. The results suggest that earlier cardiovascular actions of partially
      purified CDS were either attributable to contaminating molecules and/or that CDS
      may be a family of molecules.

PMID- 7735263
TI  - In vivo voltammetry and microdialysis monitoring of monoamine metabolism in the
      rat brainstem neurons.
AB  - Two "in vivo" techniques allow the monitoring of extracellular levels of
      monoamines and related compounds in selected rat brainstem regions: voltammetry
      and microdialysis. "In vivo" voltammetry has a high regional selectivity: for
      example, we have been able to perform a subregional study and to show that the
      increase in extracellular DOPAC induced by 30 min-hypotension was twice as larg
      in the rostral as in the caudal rat locus coeruleus. The spatial resolution, as
      expressed by x 1/2 (see text), is 4 times better for voltammetry (50 microns)
      than for microdialysis (190 microns). Another advantage of voltammetry is its
      excellent time resolution. However, microdialysis has a much better biochemical
      specificity than voltammetry. Furthermore it allows some enzymatic activities,
      such as tyrosine hydroxylase, to be measured almost continuously in
      catecholaminergic brain nuclei. From a functional point of view, the results of
      our experiments (alpha 2 ligand administration, arterial hypotension or stress)
      illustrate the respective interest and complementarity of these two "in vivo"
      techniques. Their current developments will lead to a better temporal and
      biochemical resolution combined with an increase in the number of substances
      analyzed "in vivo", including peptides and nitric oxide.

PMID- 7735264
TI  - Central monoamine systems and new antihypertensive agents.
AB  - This review describes the relationship between central monoamine pathways and
      centrally acting antihypertensive agents. By using antagonists with affinity for
      alpha 2-adrenoceptors and also imidazoline receptors we have found that the first
      generation agents clonidine and alpha-methyldopa activate alpha 2-adrenoceptors
      while the newer second generation antihypertensive agents rilmenidine and
      moxonidine activate imidazoline receptors. Despite the difference in receptors
      activated, the hypotension produced by central administration of all agents was
      attenuated after chemical lesioning of the brainstem noradrenergic or
      serotonergic pathways suggesting a similar dependence on central monoamine
      pathways. Since the acute 6-hydroxydopamine-induced release of noradrenaline in
      the brainstem produces hypotension it suggests that these agents normally mimic
      brainstem noradrenergic function. By contrast the pressor response shortly
      following 5,6-dihydroxytryptamine suggests serotonergic neurones in the brainstem
      are pressor and that part of the anti-hypertensive action of centrally acting
      antihypertensive agents is mediated by inhibition of bulbar serotonergic
      pathways. We suggest that the similar haemodynamic and baroreflex effects of the
      two generations of agents can be explained by the alpha 2-adrenoceptors and the
      imidazoline receptors being in series along the noradrenergic and serotonergic
      pathways.

PMID- 7735266
TI  - Integration in the ventral medulla and coordination of sympathetic, pain and
      arousal functions.
AB  - The nucleus paragigantocellularis lateralis (PGi) in the rostral ventral medulla
      is implicated in several functions including cardiovascular control, respiration,
      pain and analgesia. More recent studies implicate this region in alertness and
      attention as well, by virtue of its prominent projections to the nucleus locus
      coeruleus (LC). To investigate information that is integrated in the PGi, we used
      tract tracing to examine brain and spinal projections to this region. Afferents
      to PGi were found to be functionally diverse and topographically organized.
      Projections to the retrofacial PGi are primarily autonomic in nature. A wider
      range of inputs were found to target the rostral (juxtafacial) aspect of the PGi,
      including brain nuclei involved in the processing of somatosensory and auditory
      stimuli, as well as autonomic areas. Efferent projections to the LC were also
      examined in detail. Neuropharmacology experiments revealed that the PGi provides
      a potent excitatory amino acid input to the LC and an inhibitory input acting at
      alpha 2 receptors on LC neurons. PGi neurons projecting to the LC stained for
      markers of adrenaline, enkephalin, GABA and corticotropin releasing factor.
      Finally, some PGi neurons collateralize to innervate both the LC and the spinal
      cord. These results suggest that the LC may function in parallel to peripheral
      autonomic systems providing a cognitive complement to sympathetic function, and
      that the PGi may integrate a wide range of inputs to facilitate adaptive
      responses to urgent environmental events.

PMID- 7735265
TI  - Effects of beta-adrenergic blockade on short-term variability of blood pressure
      and heart rate in essential hypertension.
AB  - Short-term fluctuations in blood pressure (BP) and heart rate (HR) were analysed
      in a group of twelve males with essential hypertension. Indirect finger BP was
      measured by a Finapres device. The effect of a 7-day administration of a
      cardioselective beta-adrenoceptor blocker, acebutolol (400 mg/day), was studied
      in a double-blind, randomized, placebo-controlled cross-over study. Compared with
      placebo, acebutolol caused a significant decrease in BP and HR. In addition, the
      standard deviation (SD) of BP and HR were reduced after acebutolol in the
      standing position. Spectral analysis of fluctuations in BP showed a reduction in
      the variability underlying the SD changes of BP and HR. This reduction
      predominated in the mid frequency (MF) region corresponding to Mayer waves. This
      effect was marked for HR since the MF component for standing HR after acebutolol
      was 46% the placebo level. The average reduction in MF component for standing
      Systolic BP (SBP) was 36%. No significant correlation was found between the Mayer
      wave reduction and the systolic, diastolic BP or HR lowering effect of
      acebutolol. No significant changes in the gain of the transfer function between
      MF SBP and HR fluctuations in the standing position were observed. The reduced MF
      component of HR and BP variability after acebutolol could be due to a peripheral
      cardiac and non-cardiac sympatholytic effect of chronic beta-adrenoceptor
      blockade.

PMID- 7735267
TI  - Working model of the sympathetic chemoreflex in rats.
AB  - This review examines the neural network responsible for activation of the
      sympathetic vasomotor system during stimulation of carotid chemoreceptors (CC) in
      anesthetized vagotomized rats (sympathetic chemoreflex, SChR). Based on unit
      recording studies and experiments designed to impair synaptic transmission within
      selected lower brainstem nuclei or subregions, a model of the SChR is proposed
      with the essential features: i) key role of the nucleus of the solitary tract
      (NTS), rostral ventrolateral medulla (RVL) and ventrolateral pons (A5 area), ii)
      no role for caudal ventrolateral medulla (CVL), iii) modulatory role of
      dorsolateral pons and pre-Botzinger area, iv) dual control of bulbospinal
      presympathetic (preS) cells by CC inputs, one via the central respiratory network
      and the other through a direct excitatory pathway independent of the activity of
      this network, and v) independent medullary pathways for SChR and baroreflex until
      the preS neuronal stage in RVL.

PMID- 7735268
TI  - The functional significance of the 10-Hz sympathetic rhythm: a hypothesis.
AB  - This paper reviews work from our laboratory on the 10-Hz rhythm in sympathetic
      nerve discharge of the cat and offers a hypothesis on its functional
      significance. The rhythm is ubiquitous to the discharges of sympathetic nerves
      with different cardiovascular targets and arises from a system of coupled
      nonlinear brain stem oscillators, each of which has a selective relationship with
      a different portion of the spinal sympathetic outflow. The 10-Hz rhythmic
      discharges of sets of sympathetic nerves are differentially related and the
      pattern of relationships in one experiment can be the reverse of that in the
      next. We hypothesize that nonuniform and dynamic coupling of the central circuits
      controlling different sympathetic nerves is the basis for the formulation of
      complex cardiovascular response patterns that include differential changes in
      regional blood flows.

PMID- 7735269
TI  - Use of c-fos functional mapping to identify the central baroreceptor reflex
      pathway: advantages and limitations.
AB  - Prolonged stimulation of many neurons results in the expression of the immediate
      early gene c-fos, which in turn cause the production of the protein Fos, whose
      presence in a cell can be detected by immunocytochemistry. This method has been
      used in both conscious and anaesthetized animals to identify central neurons
      involved in the baroreceptor reflex. In this paper we review the factors that can
      influence c-fos expression, with particular emphasis on the effects of different
      anaesthetic agents. We conclude that the c-fos method of functional mapping, when
      applied carefully and critically, is a very useful method of identifying central
      neurons that are activated by cardiovascular stimuli in conscious animals.
      Anaesthetic agents can significantly alter c-fos expression, and this effect
      differs greatly according to the type of anaesthetic used.

PMID- 7735270
TI  - Functional anatomy of sympathetic premotor cell groups in the medulla.
AB  - Pre- and postganglionic sympathetic neurons are organized into discrete
      functional channels, according to the target they supply. The activity patterns
      which they show differ between channels, implying that the CNS pathways driving
      them are not the same. Premotor neurons probably play a key role. This article
      focuses on what recent evidence tells us about the organization of premotor
      neurons which control specific sympathetic outflows. Cells that drive muscle
      vasoconstrictor (MVC), cutaneous vasoconstrictor (CVC), visceral vasoconstrictor
      (VVC) and renal sympathetic (RSN) outflows have been identified among the
      premotor neurons of the rostral ventrolateral medulla (RVLM). Other vasomotor,
      cardiac or adrenal drives are also represented in that cell group. Neurons
      driving sudomotor responses have been localized in the rostral ventromedial
      medulla. Evidence on the specific functions of other premotor cell groups is
      briefly discussed.

PMID- 7735271
TI  - Coordination of sympathetic and respiratory systems: neurophysiological
      experiments.
AB  - Many sympathetic neurons exhibit respiratory rhythmicity in their activity which
      is due to a central coupling between respiratory neurons and neurons of autonomic
      pathways. The presence or absence and the pattern of this respiratory modulation
      depend on the function of sympathetic neurons and on the way by which both
      systems are coupled. In the cat, neurons supplying resistance vessels such as
      muscle vasoconstrictor and visceral vasoconstrictor neurons are activated during
      inspiration and suppressed during postinspiration. In contrast, most cutaneous
      vasoconstrictor neurons show no respiratory modulation in their activity, some
      are inhibited during inspiration and activated during expiration, and others
      exhibit a weak peak during inspiration. Sudomotor neurons are preferentially
      active during postinspiration and "inspiratory-type" neurons only during
      inspiration. In addition to the central coupling between presympathetic and
      respiratory neurons, cardiovascular afferents, notably the arterial
      baroreceptors, contribute an important peripheral reflex component of respiratory
      modulation, but only in neurons of muscle and visceral vasoconstrictor pathways.

PMID- 7735272
TI  - Abdominal vagal inputs to catecholamine neurons in the ventrolateral medulla.
AB  - Stimulation of the abdominal vagus nerve increases arterial pressure and causes
      secretion of vasopressin. We have shown in rabbits that the arterial pressure
      increases are mediated by activation of barosensitive bulbospinal neurons in the
      C1 region of the rostral medulla. Secretion of vasopressin involves activation of
      neurons in the A1 region of the caudal ventrolateral medulla. Neuroanatomical
      studies with Fos indicate that approximately 50% of the C1 area cells are C1
      neurons. Approximately 70% of the A1 area cells are A1 neurons. These neurons may
      mediate physiological responses occurring during abdominal malaise resulting from
      ingestion of toxins. Our discovery of a major excitatory input to A1 and C1
      neurons from the abdominal vagus should prove useful in studies of the function
      of these neurons.

PMID- 7735273
TI  - The brain renin-angiotensin system: molecular mechanisms of cell to cell
      interactions.
AB  - The components of the Renin-Angiotensin System (RAS) have been found to be
      expressed in the brain. Angiotensinogen, the high molecular weight precursor of
      the system, is widely distributed and expressed in areas not related to control
      of blood pressure and body fluid homeostasis as well. It has been shown that it
      is regulated by steroid hormones independently from the liver and that it is also
      regulated in a different manner in several brain areas. Angiotensin II, the
      effector peptide of the system, may be generated in the brain via the classical
      pathway, using renin and angiotensin converting enzyme or directly from
      angiotensinogen by cathepsin G or tonin. N-terminal peptides of angiotensin II
      have been found in several brain areas with ANG (1-7) involved in vasopressin
      release however without influence on blood pressure and with ANG III acting as
      potent as ANG II. Transgenic animals may be used to study the pathophysiology of
      an activated brain RAS.

PMID- 7735274
TI  - Interactions of angiotensin II with central catecholamines.
AB  - There is a large body of anatomical and functional evidence supporting an
      interaction between brain angiotensin and central catecholamine systems.
      Angiotensin II AT1 receptors have been identified on dopamine containing cells in
      the substantia nigra and striatum of human brain using receptor autoradiography.
      Using in vivo microdialysis we have demonstrated that locally administered
      angiotensin II stimulates dopamine release from the striatum of conscious rats.
      Since some angiotensin receptor antagonists and angiotensin converting enzyme
      inhibitors can cross the blood brain barrier it is possible that they interact
      with the brain catecholaminergic systems.

PMID- 7735275
TI  - Angiotensin as neuromodulator/neurotransmitter in central control of body fluid
      and electrolyte homeostasis.
AB  - Stimulation of central angiotensin receptors promotes, among others, drinking
      behaviour, stimulation of natriuresis and increased release of vasopressin.
      Angiotensin (ANG II)-containing pathways in the lamina terminalis and the
      hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, brain areas
      involved in the regulation of body fluid homeostasis, have been described. All
      these areas express predominantly AT1 receptors. The drinking response and the
      vasopressin release to centrally administered ANG II are mediated by AT1
      receptors, while AT2 receptors exert inhibitory effects. Evidence for the
      involvement of the catecholaminergic and angiotensinergic pathways in the PVN and
      SON in mediating the ANG II-induced release of vasopressin is presented. ANG II
      is released in the PVN upon local osmotic stimulation and water deprivation.
      Finally, we present evidence that activation of central angiotensinergic
      receptors, water deprivation, or hypertonicity induce transcription of immediate
      early genes and expression of the respective proteins in the lamina terminalis
      and in the PVN and SON. The summarized data implicate ANG II as a
      neuromodulator/neurotransmitter in central control of body fluid and electrolyte
      homeostasis.

PMID- 7735276
TI  - Angiotensin II-dependent hypertension and the arterial baroreflex.
AB  - Angiotensin II (ANG II)-dependent hypertension involves the resetting of the
      heart rate (HR) and sympathetic baroreflex toward higher pressures in conscious
      rabbits. The resetting of the HR baroreflex function occurs within minutes of the
      administration of ANG II, while the resetting of the sympathetic baroreflex
      requires several days. In conscious rabbits, an intact area postrema (AP) is
      required for the resetting of either the HR or sympathetic baroreflex function.
      Data is also presented showing that pretreatment with an alpha-1 adrenergic
      receptor antagonist prevents the early resetting of the HR baroreflex.

PMID- 7735277
TI  - The spinal organisation of the baroreceptor reflex.
AB  - Baroreceptor inhibition of a spinally evoked response in a renal nerve was
      studied following removal of excitatory drive from the rostral ventrolateral
      medulla (RVLM), by microinjecting glycine into this region (RVLM block).
      Activation of arterial baroreceptors was still able to inhibit a spinally evoked
      response after RVLM block and this effect was abolished by intrathecal
      strychnine. Intrathecal bicuculline also was shown to reduce the magnitude of the
      baroreceptor inhibition but only when the RVLM was intact indicating that
      bicuculline was removing a facilitation. Both strychnine and bicuculline
      antagonised an NTS induced inhibition of activity in single sympathetic
      preganglionic neurones. It is concluded that arterial baroreceptor reflex
      regulation of vasomotor activity occurs at a spinal as well as a supraspinal site
      and GABA and glycine are the likely inhibitory mediators at both sites.

PMID- 7735278
TI  - Integrative properties of sympathetic preganglionic neurones within the thoracic
      spinal cord.
AB  - The discharge pattern of sympathetic preganglionic neurones (SPNs) in the lateral
      horn is shaped by the interplay of synaptic inputs, membrane properties and local
      factors within the spinal cord. Intracellular recordings in vivo and in vitro
      have clarified the importance of some of these factors. Pacemaker activity can be
      recorded in vitro, but does not contribute to the generation of action potentials
      in vivo where spikes are solely generated from synaptic potentials. Synaptic
      potentials occur in phase with either the cardiac or the respiratory cycle or at
      irregular intervals. Postsynaptic interaction of these various inputs at the
      level of SPNs as well as presynaptic gating mechanisms in relation to the
      respiratory cycle have been observed. The discharge pattern is also modified by
      specific membrane properties which function to limit their discharge rate in the
      absence of axon collaterals. Finally the discharge of SPNs is affected by local
      factors: Since asphyxia causes a strong sympathetic activation when synaptic
      inputs to other neurones are already non-functioning synapses on SPNs are
      resistant to hypoxia or changes in the extracellular fluid somehow influence the
      activity of these neurones.

PMID- 7735279
TI  - The one hundred percent hypothesis: glutamate or GABA in synapses on sympathetic
      preganglionic neurons.
AB  - The synaptic input from glutamate- or gamma-aminobutyric acid (GABA)
      immunoreactive nerve fibers to sympathetic preganglionic neurons projecting to
      the superior cervical ganglion was assessed using retrograde tracing with cholera
      toxin B subunit and post-embedding immunogold labelling. Half the boutons that
      synapsed on or directly contacted this group of neurons were immunoreactive for
      glutamate and half were immunoreactive for GABA. In previous studies, about 2/3
      of the synapses on sympathoadrenal neurons were found to be glutamate
      immunoreactive and about 1/3, GABA immunoreactive and these two amino acids were
      not co-localized. Thus, 100% of the boutons that synapse on sympathetic
      preganglionic neurons supplying the superior cervical ganglion or the adrenal
      medulla are likely to contain either glutamate or GABA. Anterograde tracing
      combined with amino acid immunocytochemistry indicated that at least some
      glutamate-containing and some GABA-containing nerve fibers in the
      intermediolateral cell column could come from the rostral ventral medulla.

PMID- 7735280
TI  - Properties of preganglionic and postganglionic neurones in vasoconstrictor
      pathways of rats and guinea pigs.
AB  - The electrophysiological properties of pre- and postganglionic neurones and their
      synaptic inputs have been examined in both in vivo and in vitro preparations.
      Electrically, both neurone types have similar low resting conductance and compact
      dendritic trees. In preganglionic vasoconstrictor neurones, both slow and fast
      excitatory and fast inhibitory potentials are probably involved in baroreceptor
      reflexes, discharge being initiated after summation. In contrast, postganglionic
      vasoconstrictor neurones receive only one type of fast excitatory input. One of
      the converging preganglionic inputs has a very high safety factor and always
      fires the postganglionic neurone ensuring that the centrally-derived pattern of
      discharge reaches the neurovascular junctions. We do not know if the other
      subthreshold inputs summate during natural activity in vivo, as it is not known
      whether functionally distinct preganglionic inputs converge on vasoconstrictor
      neurones in ganglia.

PMID- 7735281
TI  - Reflex and morphological changes in spinal preganglionic neurons after cord
      injury in rats.
AB  - Autonomic dysreflexia manifested as episodic hypertension after spinal cord
      injury may occur because of changes in sympathetic preganglionic neurons (SPNs)
      in response to loss of bulbospinal inputs. We studied dysreflexia in rats one
      week after midthoracic spinal cord hemisection or complete transection. After
      cord hemisection at the fifth thoracic segment all rats had hemiparaplegia and
      after complete transection they were paraplegic and exhibited dysreflexia
      characterized by pressor responses to distension of the urinary bladder. Changes
      in morphology of SPNs retrogradely labelled by cholera toxin and Fluoro Gold were
      examined and changes also were assessed in expression of the synaptic vesicular
      protein synaptophysin. A comparison of SPNs rostral and caudal to the lesion
      revealed significant dendritic degeneration and decreased soma size after the
      loss of supraspinal input. Expression of synaptophysin was normally observed
      rostral to a cord hemisection but this immunoreactivity was increased caudal to
      the lesion. In conclusion significant structural changes in SPNs occur within a
      week after cord injury. The abnormal cardiovascular control and exaggerated
      reflex reactions may be due to new synapse formation on these SPNs.

PMID- 7735282
TI  - The defense reaction: a common denominator of coronary risk and blood pressure in
      neurogenic hypertension?
AB  - In addition to high blood pressure, patients with hypertension often have insulin
      resistance, dyslipidemia and increased sympathetic tone. An increased sympathetic
      tone can negatively affect glucose utilization through three distinct mechanisms;
      a direct beta-adrenoreceptor-mediated insulin resistance, through conversion to
      more insulin resistant fast twitch fibers and through alpha-adrenergic
      vasoconstriction which may decrease the delivery of insulin and glucose to the
      skeletal muscle cells. The insulin resistance in turn may be responsible for the
      observed dyslipidemia in hypertension. The sympathetic overactivity in
      hypertension reflects a chronic activation of defense/vigilance reaction. The
      increase of cardiac output, blood pressure and insulin resistance in the course
      of the defense reaction are viewed as an appropriate preparatory response to
      facilitate muscular exercise (through higher cardiac output and increased
      pressure) and preserve (through insulin resistance) the optimal supply of glucose
      to the brain. The defense reaction may have been useful in evolution and may have
      offered survival advantage. In modern times with prolonged life expectancy the
      previously useful response (in evolutionary terms) contributes to a faster and
      deleterious wear and tear of the cardiovascular system.

PMID- 7735283
TI  - Baroreceptor control of the circulation in man. An update.
AB  - In recent years assessment of baroreflex cardiovascular control in humans has
      received growing attention for two major reasons, i.e. 1) the availability of new
      techniques to evaluate this reflex function and 2) the possibility that a
      baroreflex alteration might play a role in the clinical evolution of
      cardiovascular diseases. This paper will briefly examine the alterations in
      baroreflex function in a variety of diseases affecting the circulation. In
      particular it will be focused on 1) the baroreflex control of heart rate and
      microneurographically measured muscle sympathetic nerve traffic in human
      hypertension, 2) the impairment of this reflex homeostatic function occurring in
      congestive heart failure of different clinical severity and finally 3) the
      transient alterations in baroreflex-heart rate control occurring in man in the
      acute post-myocardial infarction phase and during episodes of spontaneous
      myocardial ischemia.

PMID- 7735284
TI  - Mechanisms of insulin action on sympathetic nerve activity.
AB  - Insulin resistance and hyperinsulinemia may contribute to the development of
      arterial hypertension. Although insulin may elevate arterial pressure, in part,
      through activation of the sympathetic nervous system, the sites and mechanisms of
      insulin-induced sympathetic excitation remain uncertain. While sympathoexcitation
      during insulin may be mediated by the baroreflex, or by modulation of
      norepinephrine release from sympathetic nerve endings, it has been shown
      repeatedly that insulin increases sympathetic outflow by actions on the central
      nervous system. Previous studies employing norepinephrine turnover have suggested
      that insulin causes sympathoexcitation by acting in the hypothalamus. Recent
      experiments from our laboratory involving direct measurements of regional
      sympathetic nerve activity have provided further evidence that insulin acts in
      the central nervous system. For example, administration of insulin into the third
      cerebralventricle increased lumbar but not renal or adrenal sympathetic nerve
      activity in normotensive rats. Interestingly, this pattern of regional
      sympathetic nerve responses to central neural administration of insulin is
      similar to that seen with systemic administration of insulin. Further, lesions of
      the anteroventral third ventricle hypothalamic (AV3V) region abolished increases
      in sympathetic activity to systemic administration of insulin with euglycemic
      clamp, suggesting that AV3V-related structures are critical for insulin-induced
      elevations in sympathetic outflow.

PMID- 7735285
TI  - Endothelin, cerebral ischaemia and infarction.
AB  - Endothelin-1 (ET-1) is a 21 aminoacid peptide with potent vasoconstrictor
      properties. It is synthesised and released by endothelial cells in both the
      peripheral and cerebral vasculature and is also localised within neurones in
      discrete brain areas where it may contribute to the central regulation of blood
      pressure. We have shown that intracisternal ET-1 in conscious rats induces a
      marked pressor response that is associated with an intense widespread reduction
      in cerebral blood flow. Subsequent studies with local application of ET-1 to the
      middle cerebral artery (MCA) revealed a dose dependent reversible
      vasoconstriction of the artery that resulted in profound reductions in local
      cerebral blood flow and the development of cerebral infarction. Thus abluminal
      application of ET-1 to the MCA offers a simple model of reversible focal cerebral
      ischaemia in the rat that complements the existing models of permanent MCA
      occlusion. The ET-1 model will help to provide new insights into the mechanisms
      of cerebral ischaemia and reperfusion injury, and to evaluate the usefulness of
      novel strategies of neuroprotection.

PMID- 7735287
TI  - Cardiac baroreflex in hypertension: role of the heart and angiotensin II.
AB  - Sigmoid logistic function curves provide a powerful means of characterizing the
      baroreceptor-heart rate reflex. In hypertension the operating range of the reflex
      is reset in the direction of the elevated resting BP; this can be accounted by
      rapid resetting of the threshold of the arterial baroreceptors. In addition,
      there is a deficit in the vagal component of the heart rate (HR) range. Reduction
      in gain occurs in moderate/severe hypertension, but may be absent in young
      primary hypertensives. All the changes are reversible, and reversibility of HR
      range and gain is related to reducing left ventricular hypertrophy or central
      blood volume rather than to reduction in BP. High plasma angiotensin II can
      further accentuate the vagal deficit. An input-output model has been developed
      from comparison of perivascular cuff and drug methods for eliciting the reflex,
      which place different loads on the heart; the greater load changes simulate many
      of the alterations in reflex properties observed in hypertension. We conclude
      that during changes in vasomotor tone in normal animals, about 70% of the drive
      for the cardiac baroreflex comes from arterial baroreceptors and about 30% from
      low threshold cardio-pulmonary baroreceptors. In hypertension, the vagal deficit
      in HR range is due to afferent interactions involving arterial and low and high
      threshold cardio-pulmonary baroreceptors.

PMID- 7735288
TI  - Criteria for intracellular identification of pre-sympathetic neurons in the
      rostral ventrolateral medulla in the rat.
AB  - Previous studies revealed that a relatively small group of reticulospinal neurons
      located in the rostral ventrolateral medulla (RVLM) plays a key role in the
      generation of resting vasomotor tone and in reflex control of arterial blood
      pressure. These medullary pre-sympathetic neurons have been extensively studied
      with extracellular microelectrodes, but so far few attempts have been made to
      examine their intracellular properties in vivo. This report, based on
      intracellular recordings from 8 RVLM pre-sympathetic neurons in anaesthetised
      rats, sets out criteria for intracellular identification of such neurons. We
      propose that two features are sufficient to classify RVLM neurons as pre
      sympathetic during intracellular recording: inhibitory response to stimulation of
      the aortic depressor nerve with short bursts of pulses applied at low frequency;
      and antidromic stimulation from the upper thoracic segments. Cardiac oscillations
      in the membrane potential or responses during large changes in blood pressure can
      be due to movement artefact, and are therefore not reliable as a means of
      demonstrating baroreceptor input. Further intracellular studies of these neurons
      will undoubtedly result in further progress in understanding their function.

PMID- 7735289
TI  - c-fos expression in central cardiovascular pathways.
AB  - Injection of muscimol in the caudal ventrolateral medulla increases blood
      pressure and stimulates neuronal c-fos expression in the rostral ventral medulla
      (RVM). The blockade of c-fos expression in the RVM by antisense oligonucleotides
      attenuates the blood pressure response to this muscimol-induced disinhibition of
      the RVM and also reduces resting blood pressure. The results suggest that
      cardiovascular neurons in the RVM express c-fos and that the basal and stimulated
      expression of the c-fos gene is important in the central regulation of blood
      pressure.

PMID- 7735286
TI  - Central nervous system noradrenergic control of sympathetic outflow in
      normotensive and hypertensive humans.
AB  - We applied transmitter washout methodology, sampling internal jugular venous
      plasma via a percutaneously placed catheter, to study CNS norepinephrine release
      in humans and its relation to peripheral sympathetic activity. Norepinephrine
      overflows into the venous drainage of the brain, as do its precursor, DOPA, and
      metabolites DHPG and MHPG, indicating that the blood-brain barrier provides an
      incomplete impediment to their outward flux from the brain. Pharmacological
      testing with two drugs which altered CNS norepinephrine turnover, the tricyclic
      antidepressant desipramine and the ganglionic blocker, trimethaphan, demonstrated
      a direct relation existed between CNS norepinephrine release and sympathetic
      nerve firing rates. In essential hypertension, the sympathetic activation
      commonly present was associated with, and possibly caused by increased CNS
      release of norepinephrine, manifested in elevated overflow of norepinephrine,
      MHPG and DHPG from the brain. Bilateral jugular sampling, coupled with a cerebral
      venous sinus scan to delineate the drainage pattern, demonstrated that this
      increased norepinephrine release was confined to subcortical forebrain regions.

PMID- 7735290
TI  - Excitatory amino acid receptors in central cardiovascular regulation.
AB  - Excitatory amino acid neurotransmitters and their receptors are the principal
      mediators of fast synaptic transmission within the central nervous system.
      Accumulating evidence suggests that synaptic activation of excitatory amino acid
      receptors in the nucleus of the tractus solitarius, rostral and caudal
      ventrolateral medulla, and in the spinal cord play a key role in neural
      transmission of cardiovascular information in the central nervous system.
      Pharmacological blockade of excitatory amino acid receptors at these sites
      eliminates a variety of centrally-mediated cardiovascular responses. These
      include baroreceptor reflexes and increases in arterial pressure produced by
      stimulation of various brain regions as well as peripheral afferent nerves. These
      observations indicate that synaptic activation of EAA receptors at specific sites
      within the brainstem and in the spinal cord play an important role in central
      cardiovascular regulation.

PMID- 7735291
TI  - The tachycardia associated with the defense reaction involves activation of both
      GABAA and GABAB receptors in the nucleus tractus solitarii.
AB  - In urethane-anesthetized rats, the tachycardia associated with the defense
      reaction can be elicited by unilateral microinjections of the GABAA-antagonist,
      bicuculline methyliodide (BMI, 20 pmol), into the dorsomedial nucleus (DMN) of
      the hypothalamus. This effect is thought to be mediated via a pathway that
      activates GABAergic interneurons in the medullary nucleus tractus solitarii (NTS)
      which, in turn, inhibit vagal outflow to the heart. Ipsilateral intra-NTS
      microinjection of BMI (10 pmol) or the GABAB-antagonist, 2-OH-saclofen (400
      pmol), attenuated the tachycardia elicited from the DMN. The tachycardia was also
      inhibited by intra-NTS administration of the NMDA-receptor channel blocker, MK
      801 (30 pmol), or the non-NMDA antagonist, CNQX (400 pmol). These findings are
      interpreted to indicate that a) GABAergic control of heart rate at the level of
      the NTS is mediated by both GABAA and GABAB receptors, and b) descending input
      from the DMN to the NTS releases GABA via glutamate acting on ionotropic
      glutamate receptors located on GABAergic interneurons.

PMID- 7735292
TI  - Mortyn Jones Memorial Lecture. Limbic regions mediating central actions of
      oxytocin on the milk-ejection reflex in the rat.
AB  - Central oxytocin administration has a profound facilitatory effect on the
      patterning of the milk-ejection reflex in the lactating rat. Lesion and
      microinjection studies indicate that this action is, in part, mediated via a
      population of limbic neurones in the bed nuclei of the stria terminalis and
      ventrolateral septum, which have been shown to possess oxytocin receptors and to
      be activated by selective oxytocin-receptor agonists in vitro. In vivo
      electrophysiological recordings reveal that some of these neurones display
      cyclical activity which is highly correlated to each milk ejection, and are
      rapidly activated following i.c.v. administration of oxytocin, coincident with
      the facilitation of milk ejection activity. A hypothetical model is proposed in
      which this population of limbic neurones serves to gate the activity of a
      pacemaker which, in turn, coordinates the bursting of hypothalamic magnocellular
      neurones. The oxytocin innervation of these neurones and their expression of
      oxytocin receptors increases in the postpartum period, and the resultant enhanced
      sensitivity leads to a greater facilitatory response during lactation. Inhibitory
      opioid and noradrenergic inputs which converge on these oxytocin-sensitive
      neurones may function to switch off the facilitatory circuit during periods of
      stress. Thus, this population of limbic neurones participates in the regulation
      of neuroendocrine activity during lactation by providing an appropriate degree of
      feedback to alter the patterning of the milk-ejection reflex.

PMID- 7735293
TI  - Differential dependence of ACTH secretion induced by various cytokines on the
      integrity of the paraventricular nucleus.
AB  - Effect of different cytokines, human recombinant interleukin-1 alpha and beta (IL
      1 alpha, IL-1 beta), interleukin-6 and tumor necrosis factor-alpha (TNF) on
      adrenocorticotropin (ACTH) secretion was compared in sham-operated rats and those
      with lesions of the hypothalamic paraventricular nucleus. IL-1 alpha was less
      active than IL-1 beta in stimulating ACTH in sham-operated rats. Intravenous
      injection of IL-1 beta in sham-operated animals resulted in a rapid elevation of
      ACTH secretion. Five days after surgical lesion of the paraventricular nucleus,
      the main hypothalamic source of hypophysiotropic corticotropin-releasing factor
      41, the response to IL-1 beta was attenuated but not abolished. This suggests
      involvement of extra-paraventricular releasing factors in mediation of ACTH
      releasing activity of IL-1 beta, altered responsiveness of pituitary to CRFs,
      and/or direct action of IL-1 beta on the corticotrope cells. TNF resulted in a
      biphasic stimulation of ACTH concentration, with peaks at 15 min and 90 min. In
      paraventricular-lesioned, TNF injected rats both of these ACTH peaks disappeared,
      suggesting that CRFs from the paraventricular origin mediates ACTH-inducing
      activity of TNF. IL-6 elevated ACTH secretion much later than the other
      intravenously injected cytokines, the peak was at 1 h in sham-lesioned rats.
      Paraventricular lesion completely prevented the increase of ACTH plasma levels
      after IL-6 injection. These data suggest that: (1) Effect of TNF and IL-6 on
      hypothalamo-pituitary-adrenal axis is mediated through the hypothalamic
      paraventricular nucleus and (2) IL-1 beta is able to release ACTH even in the
      absence of hypothalamic drive.

PMID- 7735294
TI  - Role of neuropeptide Y in the regulation of tyrosine hydroxylase messenger
      ribonucleic acid levels in the male rat arcuate nucleus as evaluated by in situ
      hybridization.
AB  - Neuroanatomical data have clearly demonstrated the existence of synaptic contacts
      between neuropeptide Y (NPY) endings and tuberoinfundibular dopaminergic (TIDA)
      neurons in the rat arcuate nucleus. In order to determine the influence of NPY in
      the biosynthesis of dopamine, we have studied the effects of NPY and some NPY
      analogs on tyrosine hydroxylase (TH) gene expression in TIDA neurons in the male
      rat. The following peptides: NPY, PYY, [Leu31, Pro34]-NPY (a Y1 receptor agonist)
      and NPY13-36 (a Y2 receptor agonist) were injected into the left lateral
      ventricle of adult male rats. All the animals were perfused with 4%
      paraformaldehyde 4 h after injection. Cryostat sections through the arcuate
      nucleus were processed for quantitative in situ hybridization. The
      intracerebroventricular injection of NPY, PYY and [Leu31, Pro34]-NPY induced an
      increased of 43, 33 and 42%, respectively, in the number of grains overlying TH
      neurons. On the other hand, the Y2 receptor agonist NPY13-36 did not influence
      mRNA levels. These data then strongly suggest that NPY positively regulates the
      genetic expression of TH in rat TIDA neurons via the Y1 NPY receptor subtype.

PMID- 7735295
TI  - Similarities and discrepancies in the signaling pathway for nerve growth factor
      in an insulin producing cell line and a neural crest-derived cell line.
AB  - Like neuronal cells, insulin producing cells (beta cells) possess nerve growth
      factor (NGF) binding sites and express mRNA coding for the low- and high-affinity
      NGF receptors, p75NGFR and Trk-A respectively. Although the role of NGF on
      neuronal cells is well documented, its function on beta cells is still unknown.
      As a first step towards the elucidation of the role of NGF on beta cells, we have
      characterized both types of NGF receptors on INS-1 cells, a beta cell line
      derived from a rat insulinoma and studied some early post-receptor events by
      comparing the signaling pathway of NGF in those cells and in PC12 cells, a well
      characterized NGF-responsive cell line. By polymerase chain reaction,
      immunocytochemistry, cross-linking and Western blot analysis, we clearly
      demonstrated that Trk-A and p75NGFR, the two NGF receptors expressed in INS-1
      cells and PC12 cells are similar. Moreover, upon NGF treatment, Trk-A is
      phosphorylated on tyrosine residues in both cell types in the same dose- and time
      dependent manner. These data clearly demonstrate that the first step of NGF
      signal transduction is similar in PC12 and INS-1 cells. Although early responsive
      genes like NGFI-A and c-fos are induced in both cell types upon NGF treatment,
      the induction of c-jun expression is restricted to PC12 cells. Furthermore, the
      expression of late responsive genes, such as vgf and transin, which are induced
      by NGF in PC12 cells, are not induced in INS-1 cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7735296
TI  - Negative feedback regulation following administration of chronic exogenous
      corticosterone.
AB  - Administration of exogenous glucocorticoids is known to suppress the HPA axis and
      has been reported to occupy brain glucocorticoid receptors, eventually leading to
      down-regulation. To determine the effects of chronic corticosterone
      administration on HPA axis function, corticosterone was administered as both 25%
      and 50% corticosterone/cholesterol pellets. Rats were sacrificed 6 days after
      corticosterone pellet implantation. The 25% corticosterone pellets produced a
      small increase in morning corticosterone concentrations but no change in evening
      ACTH or corticosterone secretion. The 50% corticosterone pellets produced
      constant corticosterone concentrations of 5-6 micrograms/dl, with no circadian
      variation in corticosterone, indicating inhibition of evening ACTH and
      corticosterone secretion. The 25% corticosterone pellets produced no significant
      decrease in thymus weight or in adrenal weight; 50% corticosterone pellets
      produced significant decreases in thymus weight and adrenal weight. Neither 25%
      nor 50% corticosterone pellets produced significant decreases in GR in
      hippocampus and cortex. The 50% corticosterone pellets treatment resulted in a
      decrease in anterior pituitary POMC mRNA levels, a decrease in baseline and oCRH
      stimulated ACTH release from the anterior pituitary, and a near complete
      inhibition of the AM and PM response to restraint stress. These results suggest
      that: 1) the HPA axis was able to adjust to the small increase in glucocorticoids
      produced by the 25% cort pellets with minimal disturbances in function and 2) 50%
      corticosterone pellets exert a significant inhibitory effect on stress and
      diurnal ACTH secretion which appears to be exerted at the pituitary as well as
      possible inhibitory effects on brain.

PMID- 7735297
TI  - Pituitary adenylate cyclase activating peptide-38 (PACAP-38), PACAP-27, and PACAP
      related peptide (PRP) in the rat median eminence and pituitary.
AB  - Pituitary adenylate cyclase activating peptide (PACAP) is a member of the
      vasoactive intestinal peptide-like peptide family. It is found in the
      hypothalamus, where the PACAP precursor is processed to form PACAP-38, the C
      terminal truncated PACAP-27 and PACAP related peptide (PRP). Both PACAPs are
      potent stimulators of anterior pituitary adenylate cyclase activity, but the
      physiologically relevant anatomical sources of PACAP and possible importance of
      PRP in this regard are poorly understood. Using immunocytochemistry with epitope
      specific antisera, we now show that PACAP38-, PACAP27- and PRP-positive nerve
      fibres are all present in the rat median eminence. The major immunoreactive
      species present was PACAP38. Numerous PACAP38-immunoreactive nerve fibres were
      observed in the internal layer and a few were present in the posterior pituitary
      lobe. The external layer of the median eminence contained a few PACAP-38
      immunoreactive fibres and PACAP-38-positive nerve terminals were rarely seen in
      the perivascular portal spaces. Surprisingly, delicate PACAP-38-positive nerve
      fibres were identified in the anterior pituitary lobe intermingled between the
      pituitary cells although none of the secretory pituitary cells contained
      immunoreactive PACAP38, PACAP27 or PRP and preproPACAP mRNA was not detected in
      the gland by Northern blotting or in situ hybridization. PACAP-27- and PRP
      immunoreactive nerve fibres and terminals were found in the same locations as
      PACAP-38 although generally in lower numbers. Specific radioimmunoassays and HPLC
      revealed that PACAP-38 accounts for the vast majority of the adenohypophyseal
      PACAP-immunoreactivity, whereas PACAP-27 and PRP were found in low to
      undetectable concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735298
TI  - Naloxone disinhibits magnocellular responses to osmotic and volemic stimuli in
      chronically hypoosmolar rats.
AB  - Normonatremic and chronically hyponatremic rats were pretreated with naloxone (5
      mg/kg) or isotonic (150 mM) NaCl, then were given i.v. injections of 2 M NaCl (2
      ml) or were hemorrhaged (20 ml/kg). Baseline and post-stimulus blood samples were
      withdrawn through indwelling jugular venous catheters. Baseline levels of plasma
      vasopressin (AVP) and oxytocin (OT) were similar in both normonatremic and
      hyponatremic rats and did not change after naloxone pretreatment. Increases in
      plasma AVP and OT levels in response to both hypertonic saline and hemorrhage
      were markedly blunted in the hyponatremic rats compared to the normonatremic
      rats. Naloxone pretreatment caused augmented AVP and OT secretion in response to
      hypertonic saline stimulation and hemorrhage in both the normonatremic and
      hyponatremic rats; the magnitude of the naloxone augmentations in the
      hyponatremic rats were sufficient to normalize the OT response to hypertonic
      saline and both the OT and AVP responses to hemorrhage. Our results therefore
      suggest that endogenous opioids are likely involved in the inhibition of stimulus
      induced AVP and OT release that accompanies chronic hypoosmolality.

PMID- 7735299
TI  - Hypothalamic site-dependent effects of neuropeptide Y on gonadotropin-releasing
      hormone secretion in rhesus macaques.
AB  - In rodents and rabbits, neuropeptide Y (NPY) has a bimodal effect on gonadotropin
      releasing hormone (GnRH) secretion. Intracerebroventricular (icv) administration
      or direct infusion of NPY into the median eminence (ime) suppresses GnRH release
      in ovariectomized (OVX) animals, but stimulates GnRH release in intact or OVX
      animals treated with ovarian steroids. Specific ovarian steroid-dependent NPY
      effects are, however, not obvious in non-human primates. In OVX rhesus monkeys,
      icv administration of NPY has been shown to suppress luteinizing hormone (LH)
      secretion whereas ime infusion of NPY stimulates GnRH pulses. In such animals,
      estrogen replacement does not reverse the inhibitory NPY effect on LH release,
      although estrogen enhances the stimulatory NPY effect on GnRH secretion. These
      observations led us to speculate that the bimodal NPY effects in non-human
      primates may depend on either the site of NPY action or the nature of the steroid
      milieu. This study utilized the push-pull perfusion (PPP) technique to examine
      the effects of either ime or icv infusion of NPY on GnRH release in OVX monkeys
      treated with or without both ovarian steroids. Without exception, ime infusion of
      NPY increased GnRH concentrations in push-pull perfusates regardless of the
      steroid status of the animals. In contrast, GnRH levels were reduced during icv
      infusion of NPY in both untreated and estrogen/progesterone-treated, OVX monkeys.
      These results indicate that, unlike other mammalian species, in the rhesus monkey
      the stimulatory and inhibitory effects of NPY on GnRH release depend on the site
      of NPY infusion within the brain rather than the ovarian steroidal environment.

PMID- 7735300
TI  - Vasoactive intestinal polypeptide in the suprachiasmatic nucleus of the mink
      (Mustela vison) could play a key role in photic induction.
AB  - The present study was conducted to visualize neuropeptides in the SCN of a
      mustelid, the American mink in which seasonal cycles of reproduction rely totally
      on the annual changes in day length. At this time, data in mustelids are lacking.
      Results were obtained with in situ hybridization (ISH) using synthetic
      oligonucleotide vasopressin (AVP) and somatostatin (SOM) and with single and dual
      immunohistochemistry (IHC) performed with antisera against AVP, SOM, vasoactive
      intestinal polypeptide (VIP), gastrin releasing peptide (GRP) and met-enkephalin
      (Met-ENK) in untreated (AVP and VIP) or colchicine (SOM, Met-ENK and GRP) treated
      adult male and female mink. The most striking result, evidenced by ISH as well as
      IHC was the lack of AVP, SOM and Met-ENK immunoreactive (ir)-neurons in the SCN.
      In contrast, strongly VIP ir-perikarya were widely distributed within the SCN and
      gave rise to a dense network of fibres extending within the periventricular
      (peVA) and subparaventricular (subPVA) areas. Weakly GRP ir-perikarya were also
      observed in the median part of the SCN. Dual IHC revealed that the magnocellular
      neurons located just dorsal to the SCN, in the peVA and subPVA co-stored AVP with
      VIP, SOM or Met-ENK. The lack of SCN AVP and SOM ir-neurons, reported for the
      first time in a mammalian species, raises the question of their implication in
      the functions of the circadian pacemaker and its entrainment by the light/dark
      cycle in other species. The significance of the large neurons co-storing peptides
      in the terminal field of VIPergic fibres originating in the SCN has also to be
      determined. These results suggest that VIP could be of major importance in
      processing photic information mediating circadian entrainment and consequently
      annual rhythms.

PMID- 7735301
TI  - Subcutaneous and conjunctival vaccination with a live attenuated strain of
      Salmonella Abortusovis: effect of gestation on serological response of ewes.
AB  - Annual serological testing of flocks vaccinated by the subcutaneous route with a
      live, attenuated strain of Salmonella Abortusovis has previously demonstrated the
      persistence of agglutinating antibodies. It has however been impossible to
      determine whether the antibodies originated from the vaccination or from an
      enzootic infection. The serological response, as measured by a microtechnique of
      seroagglutination using a stained antigen, was studied in an isolated flock of 30
      adult ewes. The trial period after the subcutaneous vaccination was 34 months,
      which included 3 lambings. Ten female offspring of these ewes were also studied.
      They were vaccinated by the conjunctival route and were studied for 18 months,
      which included 1 lambing. As is common for natural or experimental infection,
      high antibody titers were obtained 10-15 d after vaccination in both groups. The
      values then decreased and rose again to significant levels at each subsequent
      pregnancy. The vaccinal strain was never isolated from vaginal swabs taken at
      each lambing and there was no suggestion of stimulation by an external antigen.
      Gestation may therefore stimulate the antibody response. This suggests that the
      immunity conferred by this vaccination may last for at least 3 lambing periods.
      The consequences of these observations on vaccination protocols and serological
      diagnosis are discussed.

PMID- 7735302
TI  - Individual fluctuations in efficacy of febantel against Muellerius capillaris in
      goats.
AB  - One hundred and eighty-seven dairy goats originating from 7 farms in western
      France were treated individually with febantel (probenzimidazole drug) at a dose
      rate of 5 mg/kg in spring 1991. Individual faecal samples were collected on d 0,
      7 and 21 post-treatment and processed for counting first stage larvae of
      Muellerius capillaris (LPG: larvae per gram of faeces). Eggs of digestive tract
      strongyles were also counted on d 0 and 7 (EPG: eggs per gram of faeces). Blood
      samples were taken on d 0 to assess pepsinogen concentration related to abomasal
      damage caused by strongyle infection. The individual characteristics of the goats
      were recorded. The procedure was repeated on the same animals in autumn 1991. The
      faecal larval count reduction (FLCR) was mainly related to farm and season: farm
      1 in the spring and farm 6 in the autumn showed a higher proportion of high
      responder (HR) goats (FLCR > 80%), whereas farm 3 exhibited a lower proportion of
      HR goats in the autumn. On the other hand, the characteristics of the goats
      (breed, physiological status, age, weight, presence or absence of wattles and
      horns) as well as the initial level of parasitism (LPG, EPG and pepsinogen
      concentration) all had a role which was limited or zero on the variability of
      response to treatment. Goats could not be individually categorized according to
      their response level because the FLCR values obtained in the spring were not
      repeated in the autumn, suggesting that other environmental parameters could be
      involved.

PMID- 7735303
TI  - [Mortality of dairy cows in an ecopathologic survey in Brittany].
AB  - Although rare, natural death in dairy cows represents a serious economical loss.
      In a sample of intensive dairy farms, the mean yearly mortality rate was
      estimated to be 0.96%. There were various causes known (metabolic, accidental,
      calving-related, respiratory) and unknown (1/3 of the cases). No significant
      annual or seasonal variation was observed, although the beginning of the grazing
      period seemed to be associated with a higher mortality rate. The cows with a
      parity of 7 or more had a higher probability of dying (mortality rate: 3.5%). The
      post-partum period was also associated with a higher number of deaths. The inter
      herd variability was significant, with mortality rates running between 0 and
      4.24%. Nutritional diseases, digestive disorders and trauma were predisposing
      factors of natural death.

PMID- 7735304
TI  - [Epidemiology of gastrointestinal helminthiasis in small ruminants in the tree
      cropping pasture zone in Senegal].
AB  - An epidemiological survey on gastrointestinal helminthiasis in 51 sheep and 51
      goats was held in the tree-cropping pasture region in Senegal from October 1990
      to September 1991. All the animals examined were infected with at least 1
      helminth species. Three trematodes (Fasciola gigantica, Schistosoma bovis,
      Amphistomatids), 2 cestodes (Moniezia expansa, Cysticercus tenuicollis) and 9
      nematodes were identified. The most important parasite in sheep was Haemonchus
      contortus while Trichostrongylus colubriformis predominated in goats. The worm
      burden in sheep was significantly higher than in goats (P < 0.001). L4 larvae of
      H contortus were found in 85-87% of the small ruminants. There was a negative
      correlation between haematocrit, number of worms and egg per gram of faeces
      during the rainy season. These results show that the gastrointestinal nematode
      burden is high during the rainy season. During the dry season (9 months)
      nutritional problems are aggravated by adult worms and residual larvae.

PMID- 7735305
TI  - [The use of gene amplification for the detection of the Aujeszky's disease virus
      in the sperm of boars].
AB  - The aim of the present study was to specify the experimental conditions for the
      use of the polymerase chain reaction (PCR) in the detection of the pseudorabies
      virus in boar semen. Boar semen was artificially contaminated by Aujeszky's
      disease virus and submitted to the PCR. The seminal plasma fraction of the semen
      was found inhibitory for PCR. An incubation of the samples with proteinase K
      followed by an extraction of the viral DNA on a glass matrix was shown to be able
      to remove the inhibition. The method was simple, rapid and allowed the detection
      of around 370 viral DNA sequences per microliter of sample. The detection of the
      amplified DNA by a specific enzymatically labelled probe could improve the
      sensitivity of the method.

PMID- 7735306
TI  - Salmonella Abortusovis experimental infection induced by the conjunctival route:
      clinical, serological and bacteriological study of the dose effect in female
      lambs.
AB  - The aim of this work was to explore the first stages of infection with Salmonella
      Abortusovis after a mucosal inoculation, and to establish an experimental model
      limiting the bacteriological investigations to the inoculation site. Four groups
      of 6 ewe-lambs were infected by the conjunctival route with decreasing doses of
      Salmonella Abortusovis. The clinical and serological survey was completed by a
      daily bacteriological examination of nasal swabs and faeces. Enumeration of
      viable bacteria was performed on liver, spleen, lungs and lymph nodes harvested
      1, 8, and 22 d after inoculation. A rapid colonization of the cephalic lymph
      nodes was observed, associated with a transient spreading to prescapular and
      subiliac lymph nodes without dissemination to the liver and spleen. An irregular
      and low level faecal excretion was associated with the colonization of mesenteric
      lymph nodes. The infection by the conjunctival route may either systemically
      propagated or be locally restricted by the lymphoid system in relation to doses
      administered. This model uses low infective doses similar to those occurring in
      field conditions and offers the possibility of limiting the bacteriological
      control to the regional lymph nodes. It confirms that live attenuated Salmonella
      strains may be used as vaccinal vectors by the mucosal route.

PMID- 7735307
TI  - Comparison of resistance of various poultry lines to infection by Salmonella
      enteritidis.
AB  - A study was undertaken to determine the susceptibility or resistance of 9 outbred
      experimental or commercial poultry lines to Salmonella enteritidis PT4. Young
      chicks were inoculated either intramuscularly or orally just after hatching.
      After intramuscular challenge the lines could be divided into susceptible lines
      (LD 50% < or = 10(2) Salmonella per animal), intermediate lines (LD 50% about
      10(4) Salmonella) and resistant lines (LD 50% > 10(5) Salmonella). The results
      obtained after oral challenge confirmed these 3 groups for both mortality rates
      and the probability of the presence of salmonellae in the spleen and liver. There
      was no difference between lines concerning caecal carriage.

PMID- 7735308
TI  - Uterine collagen during pregnancy in cattle.
AB  - Uteri were collected at the slaughter of non-pregnant dairy cattle and cattle at
      various stages of gestation. The weight of the whole uterus increased about 12
      fold during the 9 month gestation period. The greatest increase was in the weight
      of the pregnant horn. The increase in weight of the uterine horns was accompanied
      by an increase in collagen content. The collagen concentration did not change.
      The collagen crosslink pyridinoline was identified in pregnant uterine tissues at
      a level of about 0.13 residues per mole of collagen; this level was the same at
      the beginning and end of pregnancy.

PMID- 7735309
TI  - A proposed division of the pestivirus genus using monoclonal antibodies,
      supported by cross-neutralisation assays and genetic sequencing.
AB  - Sixty-six pestiviruses from ruminant and porcine hosts were analysed with a panel
      of 76 monoclonal antibodies raised against 9 different viruses. Reactivity was
      used to construct epitope similarity maps for all of the viruses. Four principal
      virus subgroups were demonstrated. One subgroup equated to classical swine fever
      virus (CSFV) and included most porcine pestiviruses but none from ruminants. A
      second subgroup contained mainly viruses of bovine origin, including reference
      bovine viral diarrhoea viruses (BVDV) such as NADL; however viruses from pigs and
      sheep were also represented. A third subgroup represented by reference strains of
      border disease virus (BDV) comprised mainly ovine isolates, but also viruses from
      pigs. The fourth and most recently defined subgroup contained no reference
      strains of CSFV, BVDV or BDV, but included atypical viruses from cattle, sheep
      and pigs. The subgrouping scheme was supported by genetic comparisons between
      representative viruses from the 4 subgroups and by virus neutralisation with
      polyclonal sera.

PMID- 7735310
TI  - International Symposium on a Cellular and Molecular View of CK2. Heidelberg,
      Germany, May 1994.

PMID- 7735312
TI  - A historical view of protein kinase CK2.
AB  - The enzyme termed nowadays protein kinase CK2 was first described in liver
      extracts (as a mixture with protein kinase CK1), using casein as artificial
      substrate, by Burnett and Kennedy (1954). In 1960 it was shown that such
      casein/phosvitin phosphorylating activity was ubiquitous and distinct from
      phosphorylase kinase, i.e., the only other protein kinase known at that time. CK1
      and CK2 were distinguished from each other at the end of the sixties, and during
      the seventies CK2 was purified to homogeneity in several laboratories and
      thoroughly characterized as far as its subunit structure (alpha 2 beta 2), site
      specificity, and in vitro responsiveness to various effectors were concerned. The
      first endogenous substrate for CK2 (eIF-3) was described in 1976, but it was
      during the eighties that it became clear that CK2 is a pleiotropic protein kinase
      committed with the phosphorylation of a myriad of cellular targets. More than 100
      CK2 substrates are known, sharing typical phosphoacceptor sites specified by
      multiple acidic residues on the C terminal side of Ser/Thr. The definition of the
      primary structure of CK2 catalytic subunit, in 1987, definitely included CK2 in
      the big family of eukariotic protein kinases. The growing interest for CK2 is
      accounted for by its unusual properties, by the increasing number of its
      substrates, and by several coincidental arguments suggesting that this
      pleiotropic protein kinase plays a fundamental role in cellular regulation. A
      major and intriguing problem concerning CK2 is its apparent lack of
      regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735311
TI  - Regulation of casein kinase II by growth factors: a reevaluation.
AB  - Many of the effects of growth factors or hormones are mediated through the
      activation of protein kinase cascades. In this regard, it is well established
      that the activity of several protein kinases can be dramatically increased when
      cells are treated with a variety of stimuli. Since 1987, there have been several
      reports demonstrating that the activity of casein kinase II (CKII) can be acutely
      increased by hormones or growth factors. However, these are a number of
      discrepancies regarding the activation of CKII. In this study, we have examined
      CKII activities in extracts prepared from cells following treatment with stimuli
      that had been previously shown to elicit dramatic increases in CKII activity.
      Human WI.38 diploid lung fibroblasts were stimulated with serum or a variety of
      other stimuli including insulin, platelet-derived growth factor, fibroblast
      growth factor, epidermal growth factor, or phorbol myristate acetate. Human A431
      epidermal carcinoma cells were similarly treated with epidermal growth factor. No
      reproducible increases in CKII activity were observed in response to any of these
      treatments. By comparison, a dramatic increase in kinase activity towards a
      synthetic peptide based on phosphorylation sites within the ribosomal S6 protein
      was consistently measured. Our observations indicate that CKII is not regulated
      in a similar manner by growth factors as are the protein kinases of the MAP
      kinase cascade, e.g., MAP kinase itself or ribosomal protein S6 kinase.

PMID- 7735313
TI  - Protein kinase CK2 structure-function relationship: effects of the beta subunit
      on reconstitution and activity.
AB  - Protein kinase CK2 subunits alpha and beta were expressed either separately or
      together in a bacterial expression system (pT7-7/BL21(DE3)) and purified to
      homogeneity. After mixing the subunits, a CK2 holoenzyme (alpha 2 beta 2) was
      spontaneously reconstituted, which displays identical features as the native
      enzyme. The alpha subunit alone, although catalytically active by itself, has
      different biochemical and biophysical properties than the holoenzyme, e.g., it is
      extremely salt sensitive, already 50 mM monovalent salt can lead to a 50%
      inhibition of the catalytic activity. Furthermore, it is readily inactivated
      through urea, protease, and heat treatment. In contrast, the holoenzyme, either
      reconstituted or native, is much more stable when similar negative insults
      prevail. The beta subunit has at least three functions: (a) it is necessary for
      maximum activity of the enzyme under physiological salt conditions, (b) it
      protects the alpha subunit against denaturing agents or conditions, and (c) it
      alters the substrate specificity of the alpha subunit. By site-directed
      mutagenesis, certain functions of the beta subunit could be assigned to specific
      amino acids or domains. Twenty one mutants of the beta subunit have been prepared
      and assayed for their ability to assemble with the catalytic alpha subunit to
      give a fully competent CK2 holoenzyme. The beta subunit contains an acidic
      stretch (amino acid 55-64), which is obviously responsible for a negative control
      of enzyme activity since mutations of certain acidic amino acids within this
      stretch to alanine lead to a hyperactive CK2 holoenzyme.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7735314
TI  - Substrate specificity of protein kinase CK2.
AB  - Unlike most Ser/Thr protein kinases which recognize phosphoacceptor sites
      specified by basic residues, protein kinase CK2 is extraordinarily acidophilic in
      nature. By combining the analysis of more than 100 CK2 natural phosphorylation
      sites with the kinetic behaviour of a large number of model peptide substrates,
      it can be concluded that although the most crucial specificity determinant is an
      acidic residue (Glu, Asp, TyrP, or SerP) at position +3, additional acidic
      residues at positions spanning from -2 to +7 (and probably farther) also act as
      positive specificity determinants for CK2, whereas basic residues at these
      positions, prolyl residue at position +1, and a bulky hydrophobic doublet at
      position +1 and +2, are powerful negative determinants. It also appears that the
      nature of the acidic determinants may variably influence their effect depending
      on the position occupied: Thus, multiple aspartic acids are, in general,
      determinants as good as, or even better, than an equivalent number of glutamic
      acids; an individual Asp at position +3 flanked by Glu residues is ineffective;
      and phosphorylated residues appear to be much more effective if adjacent to the
      target residue (positions -2 to +2). In some instances, the local determinants
      alone are insufficient to account for the phosphorylation efficiency of the
      substrate which is greatly improved by the overall protein conformation, as
      illustrated by the examples of CK2 beta-subunit and protein p53, the latter
      exhibiting no consensus sequence around its phosphorylation site.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7735315
TI  - Development of inhibitors of protein kinases CKI and CKII and some related
      aspects, including donor and acceptor specificities and viral protein kinases.
AB  - A brief overview is presented of progress in the development of specific
      inhibitors of protein kinases CKI and CKII. Two promising classes of inhibitors,
      which have the ability to traverse cell membranes, are now known. One of these is
      based on halogenated benzimidazoles and 2-aza-benzimidazoles (benzotriazoles) and
      some of their nucleosides. The second embraces modified isoquinoline
      sulfonamides, several of which are known as inhibitors of other protein kinases.
      Both classes include analogs that permit discrimination between CKI and CKII.
      Ongoing research with halogenated benzotriazoles leads to inhibitors with Ki
      values below 1 microM. Also considered are nucleoside triphosphate analog
      inhibitors and their potential properties as donors, with illustrative examples
      from the field of nucleoside kinases, including the apparent existence of a dual
      specific viral protein/nucleoside kinase. The role of cellular CKII and viral
      encoded CKII-like activities in viral replication underlines the potential of
      CKII inhibitors as antiviral agents, exemplified by the case of vesicular
      stomatitis virus.

PMID- 7735316
TI  - Modes of regulation of casein kinase II.
AB  - Casein kinase II is unique when compared to other protein kinases; it utilizes
      GTP with almost the same effectiveness as ATP and exists as an active holoenzyme
      which does not need to be activated by dissociation of regulatory subunits or
      unfolding of regulatory domains. In vitro, the activity of casein kinase II is
      inhibited by acidic compounds and stimulated by basic compounds. Casein kinase II
      activity is inhibited by 2,3-bisphosphoglycerate and stimulated by polyamines at
      levels which are physiological in red cells. To examine the effects of
      autophosphorylation of the beta subunit on activity, two mutants of the
      Drosophila beta subunit have been constructed in which Ser-4 or Ser-(2-4) are
      changed to alanine residues. Analysis of autophosphorylation with wild-type and
      mutant recombinant holoenzymes reveals Ser-2 and Ser-3 as the major
      autophosphorylation sites. Autophosphorylation does not affect the
      phosphorylation of casein, but reduces the rate of phosphorylation of glycogen
      synthase by 30%, elongation factor I by 50-70%, and calmodulin by 20-40%. The
      data indicate that autophosphorylation of the beta subunit can negatively
      regulate the phosphotransferase activity of casein kinase II with physiological
      substrates. To examine regulation of casein kinase II activity by the beta
      subunit, recombinant alpha and beta subunits from human and Drosophila were
      expressed in Escherichia coli. Upon formation of the holoenzyme, the beta subunit
      stimulated the catalytic activity 4- to 5-fold. The catalytic alpha subunit
      contains the eleven conserved subdomains characteristic of all protein
      kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735317
TI  - Cloning and expression of genes coding for protein kinase CK2 alpha and beta
      subunits in zebrafish (Danio rerio).
AB  - cDNA clones coding for the alpha and beta subunits of protein kinase 2 (CK2) in
      zebrafish (Danio rerio) have been isolated. Sequencing of the cDNA clones has
      demonstrated that one contains the complete coding sequence for the beta subunit
      of CK2 while the alpha clone is truncated and lacks 183 nucleotides of the 5'
      coding region. Comparison of the deduced amino acid sequences shows an extremely
      high degree of evolutionary sequence conservation of these two proteins. Northern
      analysis of the mRNAs coding for the alpha subunit indicates that this messenger
      is present in 1 h embryos as a 3.6 Kb and a 1.9 Kb species, both of which
      decrease in 24-h embryos. In the case of beta, the major mRNA species of
      approximately 1.7 Kb maintains its level during the period of embryogenesis
      studied. In situ hybridization of early embryos, using antisense RNAs against
      alpha and beta mRNAs demonstrates temporal and tissue specific expression
      patterns. The alpha mRNA decreases after blastula, when it is evenly distributed.
      The beta mRNA is maintained at high levels between 4 and 24 h of development,
      showing in 18 h embryos a higher concentration in the developing neural tube and
      in the embryonic optic and otic vesicles.

PMID- 7735318
TI  - Modulation of the molecular organization and activity of casein kinase 2 by
      naturally occurring polyamines.
AB  - Polyamines have been reported to stimulate casein kinase 2 (CK2) in vitro. We
      have shown that the phosphorylation of different substrates is diversely
      stimulated by basic effectors and that the responsiveness of CK2 activity may be
      influenced by the overall conformation of the protein substrate but also by a
      specific interaction with the enzyme itself. Our data show that native hetero
      tetrameric CK2 is a spermine binding protein and a spermine binding site was
      identified in the N-terminal region of the beta subunit of CK2. We found that
      recombinant CK2 undergoes a progressive polymerization in low salt conditions,
      giving rise to three different polymer structures. A ring-like structure formed
      by the association of four protomers alpha 2 beta 2 was characterized by gel
      filtration, sucrose density gradient analysis and electron microscopy. Polyamines
      like spermine, when added under conditions where the enzyme preparation contains
      a mixture of various oligomers, could trigger their dissociation and their
      interconversion in the fully active ring structure. These results suggest that in
      the presence of positive effectors like polyamines, CK2 adopts a ring-like
      structural organization which may represent the active state of this kinase.

PMID- 7735319
TI  - Protein kinase CKII: possible regulation by interaction with protein substrates.
AB  - Rat liver cytosolic CKII shows heterogeneity resulting from association of the
      alpha/alpha'-subunits with the beta-subunit or with a phosphorylatable protein of
      49 kDa (pp49). Preparations of pp49 were resolved into several spots by two
      dimensional analysis which might be derived from different degrees of
      phosphorylation. pp49 was phosphorylated in vitro by purified rat liver CKII and
      to a lower extent by purified rat brain protein kinase C. In all cases,
      phosphorylation of pp49 occurred exclusively on Ser. Phosphopeptide maps of
      phosphorylated pp49 confirmed that the phosphorylation by CKII or PKC takes place
      in different sites. Prior phosphorylation of pp49 by protein kinase C had no
      significant influence on the increase of the Km value for beta-casein of CKII,
      caused by pp49. A tryptic peptide from pp49 has been recently sequenced and
      antibodies against it had been raised. The antibodies were able to recognize pp49
      in rat liver extracts as well as in HL-60 extracts what leads us to presume that
      this kind of interaction might exist in other species and tissues.

PMID- 7735320
TI  - Analysis of a novel DNA-binding protein kinase CKII-like enzyme of Chironomus
      cells.
AB  - We have previously described a Chironomus tentans nuclear 42 kDa phosphoprotein
      preferentially associated with transcriptionally active chromatin. In an attempt
      to purify and identify the kinase responsible for the phosphorylation of the 42
      kDa protein, a casein-phosvitin affinity chromatography was used. Unexpectedly,
      in the eluted kinase fraction, a novel 42 kDa casein kinase, designated protein
      kinase CK42, with a kinase activity similar, but not identical, to protein kinase
      CKII, could be identified. In other studies, a nuclear protein that comigrates
      with protein kinase CK42 in electrophoresis and is capable to bind different gene
      promoters in single-stranded forms in a sequence-selective manner was found. The
      observations that both protein kinase and ssDNA-binding activities could be
      ascribed to a 42 kDa protein raised the possibility that the ssDNA-binding 42 kDa
      phosphoprotein is a protein kinase. By specific ssDNA-binding affinity
      chromatography, using a biotinylated oligodeoxyribonucleotide promoter probe and
      Streptavidine-agarose matrix, evidence that both activities arise from the same
      protein molecules was obtained. The similarity in the enzyme activities between
      protein kinase CK42 and CKII raised the question of whether the former was an
      alpha subunit of the latter. To provide an answer to this issue, CKII, isolated
      and purified from an epithelial cell line of C. tentans, was characterized and
      compared with protein kinase CK42 purified from the same cell system. Like other
      purified CKII preparations, CKII from Chironomus is able to use ATP or GTP for
      phosphorylation of casein and phosvitin, and its activity is strongly inhibited
      by heparin and the transcription inhibitor 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole (DRB). However, the heparin and DRB sensitivities of
      protein kinase CKII were substantially higher than those of the protein kinase
      CK42. Due to their differential solubilities in NaCl and (NH4)2SO4 solutions,
      individual alpha and beta subunit pools of CKII could be detected. More than 80%
      of the nuclear alpha subunit was insoluble in 0.35 M NaCl, while all individual
      beta subunit were solubilized under the same conditions suggesting that a major
      portion of the nuclear CKII alpha subunit does not form heterooligomeric
      structures with the beta subunit, but binds tightly to nuclear components,
      probably to chromatin. The biochemical and immunological data taken together
      strongly suggest that CK42 is a novel DNA-binding protein kinase that is not the
      alpha subunit of CKII.

PMID- 7735321
TI  - Evidence for CKI and CKII at the cell surface.
AB  - Ser/Thr-protein kinases at the cell surface (ecto-PK) use physiological
      concentrations of extracellular ATP for phosphorylation of endogenous cell
      surface proteins, as well as of soluble protein substrates in the extracellular
      environment (Kubler et al., 1982, 1989). One abundant ecto-PK component is
      believed to be a protein kinase CKII since it phosphorylates phosvitin and
      casein, is sensitive to heparin at low concentrations, and can use both ATP and
      GTP as cosubstrate. This ecto-PK activity can be detached from the surface of
      intact cells through interaction with exogenous substrates, a process termed
      "shedding" (Kubler et al., 1983). This study reports a method for the
      purification and identification of shedded ecto-PK. Affinity chromatography of
      the concentrated ecto-PK through a heparin-matrix resolved two phosvitin/casein
      kinase activities upon elution with a NaCl gradient, termed as peak I and peak
      II. Relative to the total protein load of the cells employed for ecto-PK
      shedding, the specific activities increased by a factor of about 10(4) times. The
      use of peptide substrates specific for CKI and CKII, of ATP and GTP, as well as
      of antibodies specific for CKII subunit, clearly identified one of the enzymes as
      a CKI-like entity and the other one as CKII-like. Although the spatial
      arrangement on the cell surface of the two related ecto-PKs is unknown, their
      tandem appearance together in the cell supernatant might suggest the possibility
      of a functional unit.

PMID- 7735323
TI  - Human protein kinase CK2 genes.
AB  - We have analyzed the genomic structure of human protein kinase CK2. Of the
      presumably four genes, the gene encoding the regulatory subunit beta and a
      processed (pseudo)gene of the catalytic subunit alpha have been characterized
      completely. In addition, a 18.9 kb-long central part of the gene encoding the
      catalytic subunit alpha has been characterized. The subunit beta gene spans 4.2
      kb and is composed of seven exons. Its promoter region shows several features of
      a "housekeeping gene" and shares common features with the promoter of the
      regulatory subunit of cAMP-dependent protein kinase. Conforming to the genomic
      structure, the beta gene transcripts form a band around 1.1 kb. The central part
      of the subunit alpha gene contains eight exons comprising bases 102 to 824 of the
      translated region. Within the introns, 16 Alu repeats were identified, some of
      which arranged in tandems. The structure of both human CK2 coding genes, alpha
      and beta, is highly conserved. Several introns are located at corresponding
      positions in the respective genes of the nematode Caenorhabditis elegans. The
      processed alpha (pseudo)gene has a complete open reading frame and is 99%
      homologous to the coding region of the CK2 alpha cDNA. Although the gene has a
      promoter-like upstream region, no transcript could be identified so far. The
      genomic clones were used for localization in the human genome. The beta gene was
      mapped to locus 6p21, the alpha gene to locus 20p13 and the alpha (pseudo)gene to
      locus 11p15. There is no evidence for additional alpha or beta loci in the human
      genome.

PMID- 7735322
TI  - Structure and function of Saccharomyces cerevisiae casein kinase II.
AB  - Analysis of casein kinase II in organisms amenable to genetic manipulation is
      essential to elucidating the physiological function(s) of this ubiquitous protein
      kinase. This paper summarizes work from our laboratory on the enzyme from
      Saccharomyces cerevisiae. The biochemistry, molecular biology, and genetics of S.
      cerevisiae casein kinase II are reviewed and discussed.

PMID- 7735324
TI  - Regulation of transcription factors c-Myc, Max, and c-Myb by casein kinase II.
AB  - A number of transcription factors have been shown to be phosphorylated by casein
      kinase II (CKII). We have identified CKII phosphorylation sites in c-Myc, Max,
      and c-Myb which are phosphorylated in the cell. Whereas little evidence to any
      functional significance of the CKII sites in c-Myc has been obtained,
      phosphorylation of its heterodimeric partner Max alters DNA binding properties.
      CKII phosphorylation of Ser-2 and -11 in Max resulted in enhanced DNA binding
      kinetics of both Max/Max homo- and Myc/Max heterodimers without altering steady
      state binding. Replacing these serine by alanine residues and comparing the wild
      type with the mutant Max proteins in transactivation assays did not reveal any
      significant differences. For c-Myb mutational analysis of the CKII
      phosphorylation sites showed altered steady state DNA binding. Replacing Ser
      11/12 by alanine residues resulted in increased DNA binding compared to wt c-Myb
      or Myb Asp-11/12 as demonstrated by up to 10-fold differences in the dissociation
      constants. In transactivation assays, the Ala mutant showed consistently an
      increased activity both on a synthetic and on the mim-1 promoter. A potential
      CKII phosphorylation site in c-Fos was not phosphorylated in vitro. Analysis with
      peptides demonstrated that a proline residue at position +1 relative to the
      acceptor serine was inhibitory.

PMID- 7735325
TI  - Regulation of protein kinase CKII during the cell division cycle.
AB  - Protein kinase CKII is a prevalent serine/threonine protein kinase whose
      structure is highly conserved among eukaryotic organisms. Its involvement in the
      eukaryotic cell division cycle has been implicated by genetic experiments in
      yeast, antisense DNA, and inhibitory antibody experiments in mammalian cells,
      changes in activity during growth stimulation experiments, and protection of
      cells from radiation damage to replicating DNA. In addition, the cdc2 protein
      kinase, which is central to cell division cycle control, serves as a substrate
      for CKII specifically during the G1 phase of human cells. In this report,
      extracts of HeLa cells were prepared using neutral, aqueous buffers at low ionic
      strength. The cells were enriched for specific stages of the cell division cycle
      by treatment with drugs or by centrifugal elutriation. The results indicate that
      CKII activity in these extracts is highest during the G1 phase, and there appears
      to be a reduction in soluble CKII activity during the S phase. These data are
      consistent with the hypothesis that high CKII is necessary for a normal G1 phase
      but that progression through the S phase requires inhibition of CKII.

PMID- 7735326
TI  - Requirement of casein kinase 2 for entry into and progression through early
      phases of the cell cycle.
AB  - Requirement of protein kinase CK2 during cell cycle was examined by specific
      perturbation of CK2 in the intact cell by antisense-oligodeoxynucleotides and
      microinjection of antibodies. When quiescent human primary lung fibroblasts (IMR
      90) were exposed before growth stimulation to oligodeoxynucleotides complementary
      to the translation start region of mRNAs encoding subunit alpha or beta, a
      significant inhibition of growth stimulation by epidermal growth factor or serum
      was observed. The inhibition was reversible and decreased or abolished with
      mutated antisense-oligodeoxynucleotides. The inhibitory effect coincided with a
      decrease of CK2 protein (immunostaining with beta subunit antibody) at entry into
      and during the first several hours of the cell cycle. Injection of beta-specific
      monoclonal and polyclonal antibodies into IMR-90 cells caused significant
      inhibition of growth stimulation. The inhibition was reversible, not observed
      with control antibodies, and strongly reduced by coinjection of CK2 holoenzyme.
      Cytoplasmic injection inhibited up to 50-60% and was effective at two intervals
      within the first 2 h and at 12-16 h poststimulation, i.e., at G0/G1 phase
      transition and at G1/S boundary, respectively. The inhibition at G0/G1 transition
      is paralleled by an inhibition of cytoplasmic-nuclear translocation of beta
      subunit protein. Injection of beta antibodies into the nucleus inhibited growth
      stimulation by as much as 80-85% and was effective for the first 6 h
      poststimulation, i.e., at G0/G1 phase transition and progression through the
      adjoining early G1 phase. Nuclear as well as cytoplasmic injections performed
      during S phase affected neither DNA synthesis nor cell division.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7735327
TI  - Casein kinase 2 and the cell response to growth factors.
AB  - Different approaches have been followed with the aim of delineating a possible
      role of casein kinase 2 (CK2) in the mitogenic signalling in response to cell
      growth factors. (a) Immunocytochemical detection of CK2 showed that while the
      kinase is evenly distributed throughout cycle arrested cells, it becomes
      preferentially associated with the nuclear compartment in activity growing cells;
      (b) CK2 biosynthesis is activated as an early response of quiescent cells to
      growth factors. The newly synthesized CK2 steadily accumulates as the cells
      progress through the G1 phase. This growth factor-induced CK2 biosynthesis
      involves in parallel the two alpha and beta subunits of the kinase, with no
      detectable preferential subcellular localization of the newly synthesized enzyme;
      and (c) In addition to substrate phosphorylation, CK2 may form molecular
      complexes with cell components of functional significance. Such is the case with
      the protein p53, a major negative regulator of the cell cycle. CK2 forms a high
      affinity association (Kd 70 nM) with p53, through its beta subunit. The complex
      dissociates in the presence of adenosine triphosphate (ATP). These observations
      suggest that CK2 and p53 may play a coordinated regulatory role in the cell
      response to growth factors.

PMID- 7735328
TI  - Mechanism of intracellular regulation of protein kinase CK2: role of stimulus
      mediated subnuclear association.
AB  - In our studies of protein kinase CK2, or casein kinase 2, we have focused on its
      regulation in relation to altered genomic activity in response to androgen action
      (through the function of the androgen receptor) in the male accessory sex gland,
      the prostate. We have documented that androgens exert a profound effect on CK2 in
      the prostate. Investigation of androgenic regulation of the molecular expression
      of prostatic CK2 suggested that CK2 gene transcription, although substantial in
      the prereplicative phase of cell proliferation, is not an early event in androgen
      action. The lack of rapid transcriptional regulation of CK2 by androgens
      suggested an alternative mechanism for our original observations on the early
      regulation of CK2-mediated reactions. A rigorous analysis of the CK2 in different
      compartments of the prostatic cell has suggested its differential regulation. For
      example, androgen withdrawal results in a rapid loss of CK2 protein and activity
      in the prostatic cell nucleus, whereas the activity and protein in the cytosol
      undergoes a slow decline over several days. A single dose of 5 alpha
      dihydrotestosterone (5 alpha-DHT) given to 6-d castrated animals results in an
      increase in nuclear enzymatic activity as well as immunoreactive CK2 protein
      within 1 h, while a concomitant decrease is apparent in the cytosolic fraction.
      Within the nucleus, there appears to be a differential androgenic regulation of
      CK2 such that the enzyme associated with chromatin and nuclear matrix (NM)
      demonstrates a substantially greater androgen sensitivity than the enzyme in the
      nucleoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735330
TI  - A novel system to investigate the phosphorylation of the p53 tumor suppressor
      protein by the protein kinase CK2.
AB  - The tumor suppressor protein p53 is phosphorylated at a C-terminal residue
      (serine 386 in mouse p53) by the protein kinase CK2. Phosphorylation by CK2
      activates the specific DNA binding function of p53 and stimulates its ability to
      suppress cellular growth. Previous reports have suggested that phosphorylation of
      p53 at the CK2 site is stimulated in cells expressing the large tumor antigen (T
      antigen) of simian virus 40 (SV40). To test this idea, we have expressed a C
      terminal p53 "mini-protein" which comprises amino acids 154-387 of mouse p53 and
      therefore lacks the heavily phosphorylated N-terminus. In addition, the serine
      309 phosphorylation site (targeted by cyclin-dependent kinases) has been mutated
      to encode alanine. We have expressed the p53 mini-protein in mammalian cells and
      shown by phosphopeptide mapping that it is phosphorylated at a single
      physiological phosphorylation site, serine 386. Using this mini-protein as a
      cellular target for CK2, we have shown that phosphorylation of p53 by CK2 is not
      affected by the presence of T antigen. The p53 mini-protein is likely to be a
      useful tool with which to probe the regulation of p53 phosphorylation by CK2 in
      response to other factors which influence cell growth.

PMID- 7735329
TI  - Activation of rDNA transcription by FGF-2: key role of protein kinase CKII.
AB  - Basic Fibroblast Growth Factor-2 (FGF-2) promotes G1 to S transition of quiescent
      sparse adult bovine aortic endothelial cells. In addition to signal transduction
      through interaction with tyrosine kinase high affinity receptor, FGF-2 is
      translocated to the nucleus and accumulated into the nucleolus. These data
      suggest that FGF-2 functions directly in nuclear events. In vivo, correlations
      were established between the entrance of FGF-2 into the nucleus and an increase
      in rDNA transcription and in protein phosphorylation. In vitro, in experiments
      carried out with nuclei isolated from quiescent cells, addition of FGF-2
      increases rDNA transcription by a factor of 5 and also increases protein
      phosphorylation. Nucleolin, a factor involved in control of rDNA transcription is
      preferentially phosphorylated. It has been shown that nucleolin and other factors
      implicated in rDNA transcription are substrates of protein kinase CKII. Using
      purified kinase CKII and nucleolin in an in vitro phosphorylation assay, we have
      shown that FGF-2 activates the protein kinase activity. These results suggest
      that FGF-2 could act as an activator of rDNA transcription through interactions
      with the protein kinase CKII.

PMID- 7735331
TI  - The regulation of DNA topoisomerase II by casein kinase II.
AB  - DNA topoisomerase II is an essential nuclear enzyme required for the proper
      condensation and segregation of chromosomes during mitotic and meiotic cell
      division. The enzyme exists in the cell as a phosphoprotein, and it is most
      highly phosphorylated in G2 and M-phases of the cell cycle. We have shown that
      topoisomerase II is the target of casein kinase II (CKII) in yeast by comparison
      of in vivo and in vitro phosphotryptic peptide maps. Limited proteolysis and
      probing with domain specific antibodies show that with the exception of a weakly
      modified residue between aa 660 and aa 1250, all residues modified by CKII are in
      the last 200 amino acids of yeast topoisomerase II. This C-terminal domain is the
      least conserved region of the enzyme and truncation of the enzyme shows that it
      is nonessential for activity in vitro. However, the fully dephosphorylated full
      size protein is nearly inactive in decatenation assays, and activity can be
      restored by phosphorylation by CKII. To reconcile these observations, we propose
      that the C-terminal region is a negative regulatory domain, counteracted by
      phosphorylation within the domain itself. To test this hypothesis we have
      mutagenised 12 potential CKII phosphoacceptor sites in the C-terminus of
      topoisomerase II and introduced the mutant genes into a yeast strain which has a
      temperature sensitive top2 gene. The growth of the transformed strains is
      monitored at nonpermissive temperature to determine whether C-terminal
      phosphorylation is important for mitotic growth. In addition, we have purified
      the mutant enzymes to homogeneity for in vitro assays.

PMID- 7735332
TI  - Regulation of protein kinase CK2 isoform expression during rat brain development.
AB  - Protein kinase CK2 is very abundant in rat brain when compared with other rat
      tissues. The enzyme is an oligomeric protein with the structures alpha 2 beta 2,
      alpha alpha'beta 2 and alpha'2 beta 2. The alpha and alpha' subunits are
      catalytic and have a high degree of homology, whereas the beta subunit seems
      regulatory. Using specific antibodies to synthetic peptide antigens that
      discriminate among the alpha, alpha', and beta subunits of CK2, we have observed
      a significant increase in the amount of alpha' subunit during the late postnatal
      neocortical maturation period. The increased alpha' expression occurs at a
      parallel time to synaptogenesis. As for its distribution, the alpha' subunit of
      CK2 is much more abundant in neurons (particularly in large size neurons) than it
      is in glia. These results are consistent with a hypothetical role for CK2
      isoforms containing alpha' subunits in the regulation of specific functions in
      fully differentiated neurons.

PMID- 7735334
TI  - Bibliography of cellular and molecular biology research.

PMID- 7735333
TI  - Characterization of protein kinase CK2 protein subunits and p53 in F9
      teratocarcinoma cells in the absence and presence of cisplatin.
AB  - The effect of cis-diaminedichloroplatinum(II) (cisplatin) on the induction of p53
      and protein kinase CK2 activity was studied in the mouse teratocarcinoma cell
      line F9. Treatment of the cells with the chemotherapeutic agent cisplatin led to
      the detection of p53 3 h after addition of the drug. F9 cell extracts treated
      with and without cisplatin were analyzed by ion exchange chromatography for
      protein kinase CK2 alpha/beta subunits and p53 distribution. The following
      results were obtained: (a) in crude extracts of cisplatin-treated cells, CK2
      activity was sometimes reduced by as much as 50%; (b) after separation by anionic
      exchange chromatography (MA7Q, BioRad) of the crude cellular extracts from
      cisplatin-treated cells, lower CK2 activity was found in the peak fractions
      confirming the results obtained with crude cellular extracts; (c) besides the
      detection of CK2 alpha subunit by immunostaining, we have detected, at a
      concentration of approximately 200 mM NaCl, a protein of approximately 46 kDa
      which reacted with the CK2 alpha-specific antibody. This fraction was devoid of
      CK2 activity; and (d) cisplatin-treated cells exhibited p53 protein, which was
      mostly eluting ahead but also partly together with CK2 holoenzyme.

PMID- 7735335
TI  - CNS involvement in the glucose induced increase of islet blood flow in obese
      Zucker rats.
AB  - OBJECTIVES: The aim of this work was to study the role of the central nervous
      system in the glucose-induced increase in islet blood flow in obese Zucker rats.
      DESIGN: A small amount of glucose (9 mg/kg) was injected towards the brain via
      the left carotid artery in lean obese rats either intact or vagotomized and after
      a pretreatment with clonidine. RESULTS: Glucose injection induced a significant
      increase in plasma insulin level and islet blood flow without a significant
      change in plasma glucose concentration in both lean and obese rats. Prior
      vagotomy or clonidine injection resulted in a decrease in glucose-induced islet
      blood flow. Both the effect of glucose and its reversal were more pronounced in
      obese rats. CONCLUSION: In obese rats, an alteration of the CNS could result in
      an increase in the parasympathetic tone and a decrease in the sympathetic one.
      These alterations would in turn contribute to the modifications in islet blood
      flow.

PMID- 7735336
TI  - Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and
      Cushing's syndrome.
AB  - OBJECTIVES: The aim of this work was to clarify the mechanisms underlying growth
      hormone (GH) hyposecretion in Cushing's syndrome (CS) and in obesity. We studied
      the GH response to GH-releasing hormone (GHRH) alone and combined with arginine
      or pyridostigmine, two substances likely to inhibit hypothalamic somatostatin
      release. DESIGN: Three tests with GHRH alone (1 microgram/kg i.v. at 0 min) and
      combined with arginine (ARG, 0.5 g/kg infused over 30 min) or pyridostigmine (PD,
      120 mg orally at -60 min) were performed 3 days apart and in random order in
      eight women with CS (five with ACTH-dependent and three with ACTH-independent
      hypercortisolism, age 18-56, BMI 26.1 +/- 1.5 Kg/m2) and 11 with OB (age 17-54,
      BMI 42.9 +/- 2.2 Kg/m2). Eleven normal women (age 23-50, BMI 21.9 +/- 0.3 Kg/m2)
      were studied as controls (C). MEASUREMENTS: Serum GH and IGF-I levels were
      measured by radioimmunoassay. The GH secretory responses were expressed either as
      absolute values (micrograms/L) or as areas under the curve (AUC, micrograms/L/h)
      calculated by trapezoidal integration. IGF-I concentrations were expressed as
      absolute values (micrograms/L) with reference to a pure recombinant IGF-I
      preparation. RESULTS: Basal GH levels in CS were similar to those registered in
      OB (mean +/- s.e.m. 0.7 +/- 0.1 vs 0.9 +/- 0.2 microgram/L) and lower than in C
      (3.4 +/- 0.5 microgram/L, P < 0.00001). On the other hand, IGF-I levels were
      similar in all groups. The GHRH-induced GH rise in CS was lower, though not
      significantly, to that observed in OB (AUC: 65.6 +/- 13.2 vs 192.5 +/- 61.7
      microgram/L/h) and both GH responses were significantly lower than that of C
      (1029.9 +/- 98.0 micrograms/L/h, P < 0.00001). ARG enhanced the GHRH-induced GH
      release in CS (331.9 +/- 51.9 micrograms/L/h vs GHRH alone, P < 0.0001), OB
      (852.4 +/- 162.1 micrograms/L/h, P < 0.0001) and C (3362.6 +/- 386.0
      micrograms/L/h, P < 0.0002). However, the GH response to GHRH plus ARG in CS was
      lower (P < 0.002) than that in OB which, in turn, was lower than that in C (P <
      0.00001). Pyridostigmine significantly enhanced the GHRH-induced GH rise in C
      (2808.5 +/- 221.2 micrograms/L/h, P < 0.00001) and, to a lesser extent, in OB
      (627.3 +/- 84.7 micrograms/L/h, P < 0.0002) but not in CS (102.9 +/- 25.0
      micrograms/L/h). CONCLUSIONS: Our results indicate that the GH releasable pool is
      reduced in obesity and, to an even greater extent, in Cushing's syndrome. The
      inability of pyridostigmine and arginine to restore a normal GH response to GHRH
      in these conditions makes the existence of a hypothalamic somatostatinergic
      hyperactivity unlikely.

PMID- 7735337
TI  - Cardiac autonomic function in obese patients.
AB  - OBJECTIVE: The aim of this work was to determine the presence and prevalence of
      alterations in cardiac autonomic function in obese, non-diabetic subjects.
      SUBJECTS: These were 121 obese people, 15 with glucose intolerance and none with
      diabetes, and a group of 40 healthy people. MEASUREMENTS: A series of five
      standardized tests was carried out, three of which were based mainly on
      parasympathetic control (heart rate response to Valsalva, deep breathing and
      lying-to-standing) and two on cardiovascular sympathetic function (blood pressure
      response to standing and to handgrip). RESULTS: The response to the deep
      breathing test correlated negatively with age, as it did in control subjects. At
      least one parasympathetic test, age-adjusted, was abnormal in 49 patients
      (40.5%). Five other patients had an abnormal handgrip test, and no patient had
      orthostatic hypotension. No correlation was found between the parasympathetic
      test results and sex or body mass index. Prevalence of cardiac autonomic
      dysfunction, considered to be present when at least one parasympathetic test was
      abnormal, did not differ according to a gynoid or android type of obesity. A
      significant negative correlation was found between heart rate response to deep
      breathing and fasting glycemia. CONCLUSION: It was concluded that cardiac
      autonomic dysfunction evidenced by means of simple, reliable, reproducible tests
      is frequent in the non-diabetic obese subject. This disorder could explain the
      poor cardiovascular prognosis associated with obesity. Whether it is a
      complication of obesity or a marker associated with certain kinds of obesity (of
      hypothalamic origin) remains to be clarified.

PMID- 7735338
TI  - Changes in body composition and resting energy expenditure after rapid weight
      loss: is there an energy-metabolism adaptation in obese patients?
AB  - The aim of this study was to assess changes in resting energy expenditure (REE)
      related to changes in fat free mass (FFM) in nine morbid obese (BMI 43 +/- 5.1
      kg/m2) hospitalised females on VLCD. REE was measured by 30 min indirect
      calorimetry before and after 28 days of hospitalisation. Changes in FFM were
      assessed by bioelectrical impedance analysis (BIA), hydrostatic weighing (HW) and
      nitrogen balance (N). REE decreased 11.5% from 7.8 +/- 1.0 to 6.9 +/- 0.8 MJ/d.
      Total weight loss was 8.4 +/- 1.9 kg or 7.4% with an estimated FFM loss of 3.4 +/
      1.8 (BIA), 2.9 +/- 1.9 (HW) and 1.8 +/- 1.0 (N). As the fall in REE was larger
      than the loss of FFM, it is concluded that morbid obese patients develop an
      energy saving adaptation during rapid weight loss.

PMID- 7735339
TI  - Immunohistochemical, ultrastructural and morphometric evidence for brown adipose
      tissue recruitment due to cold acclimation in old rats.
AB  - OBJECTIVE: The aim of this work was to study the reactivity to chronic cold
      stress of interscapular brown adipose tissue (IBAT) in old rats by stereological,
      immunohistochemical and ultrastructural methods. DESIGN: Five 2-year-old rats
      were cold-acclimated at 4 degrees C for 4 weeks and six rats were used as
      controls (20-23 degrees C). MEASUREMENTS: The following were measured: IBAT
      volume and weight; unilocular and multilocular brown adipocyte content;
      preadipocyte number; multilocular cell mitochondrial area; cristae length and
      density per mitochondrion, and immunoreactivity for the brown adipose tissue
      specific uncoupling protein (UCP). RESULTS: Following cold acclimation, IBAT
      increased significantly in weight, volume, relative mass and number of
      multilocular adipocytes (170%). The number of unilocular adipocytes did not vary
      significantly. Multilocular adipocytes of both cold-acclimated rats and controls
      expressed the uncoupling protein, but in the experimental group cristae length
      and density per mitochondrion were significantly higher. Multilocular adipocyte
      precursors were observed in only one cold-acclimated rat but not in controls.
      CONCLUSION: The response of brown adipose tissue of old rats to chronic cold
      stimulus is similar to that observed in young and adult rats. Cold acclimation
      induces brown adipocyte recruitment: their number increases significantly, they
      test UCP-positive and their mitochondria are significantly more active than in
      controls. On the other hand, the number of unilocular adipocytes is not
      significantly affected, which may serve to improve the utilization of the heat
      produced by thermogenesis.

PMID- 7735340
TI  - A randomized trial of counseling for fat restriction versus calorie restriction
      in the treatment of obesity.
AB  - OBJECTIVE: to evaluate the effectiveness of dietary counseling focusing on fat
      reduction (20 g/day) compared to calorie reduction (1000 to 1200 kcal/day) in
      promoting long-term weight loss in moderately obese women. DESIGN: One hundred
      and twenty-two women were randomized to one of the two treatment groups and
      received intensive dietary counseling in groups of 20 over a period of 18 months.
      RESULTS: Among 74 women completing the study, weight losses at 6 months averaged
      10.2 lb (n = 39) in the fat counseling group and 8.1 lb (n = 35) in the calorie
      counseling group. Average weight returned to baseline levels in both groups over
      the succeeding 12 months despite continued intervention. CONCLUSION: Although
      these data provide little support for the immediate clinical utility of low-fat
      dietary counseling in obesity treatment, the observation that women in the low
      fat group were more compliant with treatment directions, rated the diet as being
      more palatable, and experienced greater reduction in binge eating scores suggests
      that this approach warrants further study. In addition, time dependent covariance
      analysis showed that change in fat intake predicted weight change better than
      change in total energy intake, thus reinforcing the idea that dietary fat may be
      an important factor in the etiology and treatment of obesity.

PMID- 7735341
TI  - PFK activity in muscle and heart tissue is differentially affected by dietary
      restriction.
AB  - This research examined the effect of dietary restriction on PFK activity (one of
      the enzymes in the glycolytic pathway) in selected skeletal and heart muscle
      tissue. Fifty-five Sprague-Dawley female rats were separated into three different
      groups for 10 weeks of dietary restriction: AL = ad lib fed, MR = weight reduced
      to 81% of AL and SR = weight reduced to 63% of AL. Gastrocnemius white (GW),
      plantaris, soleus (S) and heart (H) muscle tissue were dissected out and assayed
      for PFK activity. PFK activity (mumole/g/min) in GW was 105 +/- 7, 86 +/- 6 and
      61 +/- 6 for AL, MR & SR, respectively (AL > MR > SR, P < 0.05). PFK activity in
      S was 25 +/- 2, 22 +/- 1 and 16 +/- 1 for AL, MR and SR, respectively (AL, MR >
      SR, P < 0.05). In contrast, PFK activity in H was unaffected (P > 0.05). These
      data suggest that PFK activity in various muscle tissues is differentially
      affected during diet-induced weight loss.

PMID- 7735342
TI  - Binge eating disorder: response to naltrexone.
AB  - Binge eating disorder (BED) is characterized by a bulimic binge eating pattern
      without the compensatory behaviors of purging or laxative abuse. It is often
      associated with obesity. The treatment response characteristics are more like
      bulimia than other forms of obesity. We have shown the opiate antagonist
      naltrexone to attenuate bulimia nervosa in controlled clinical trials. We report
      here a response to naltrexone in a subject with BED similar to that previously
      reported for the larger population of bulimic subjects. Three consecutive periods
      of drug, placebo and double dose drug were used, with the order of the first two
      periods double blind until after the data analysis. Symptoms were reduced in the
      naltrexone compared to placebo period. Statistical significance was demonstrated
      using time series analysis for this 'n of one' study. Psychotherapy was carried
      out throughout all periods. Naltrexone plus psychotherapy may be more efficient
      than psychotherapy alone.

PMID- 7735343
TI  - Differences in conicity in young adults of European and south Asian descent.
AB  - A survey of 320 (175 male, 155 female) 19 year-old medical students showed that
      male students of South Asian origin in the top tertile for body weight or body
      mass index had a significantly greater conicity index than European males in
      these top tertiles. This difference in conicity was not significant in the group
      as a whole, or when ethnic pairs were matched for body weight or body mass index.
      However, females of South Asian descent had a significantly higher conicity index
      than females of European descent irrespective of how the groups were compared.
      The trend towards higher conicity (i.e. abdominal obesity) in young Asians may
      help explain the higher incidence of diabetes and cardiovascular disease seen in
      elderly Asians living in the United Kingdom.

PMID- 7735344
TI  - Exercise-training, macronutrient balance and body weight control.
AB  - It is well established that exercise-training can induce body weight and fat
      losses provided that mean daily energy expenditure exceeds mean energy intake.
      Recent experimental data show that under free living conditions, the composition
      of macronutrient intake tends to differ from the composition of macronutrient
      utilization when the body is in energy imbalance, even over a short period of
      time. Since protein and carbohydrate balances are precisely regulated under
      unrestricted food intake conditions, a body energy deficit is necessarily
      equivalent to a lipid deficit. In the context of an aerobic training program, a
      body lipid deficit should be spontaneously reached by performing prolonged
      vigorous exercise on a regular basis and by preventing a diet with a high fat
      content. However, as body fat decreases with exercise there is an associated
      decrease in the lipid content of the fuel mix oxidized and this acts to
      progressively decrease the lipid deficit. Ultimately, a new lipid balance will be
      reached at a reduced level of body fatness when the proportion of lipid in the
      substrate mix will become similar to the proportion of lipid in the diet. Recent
      research observations show that such a program has the potential to induce a
      substantial fat loss, particularly in the abdominal area, and a significant
      improvement of the metabolic profile of obese individuals. These beneficial
      effects cannot be maintained on a long-term basis if the new exercise and food
      habits are not incorporated in the lifestyle of these individuals.

PMID- 7735345
TI  - Sympathetically-mediated thermogenic response to food in rats.
AB  - The aim of this work was to assess the participation of the sympathetic nervous
      system in the thermogenic response to food in control and hyperphagic rats. Rats
      were fed either a control (CD) or energy dense (ED) diet. After 15 days, CD rats
      received a small (7 kJ) meal composed of either control or energy dense diet,
      while ED rats received a small meal composed of energy dense diet. The experiment
      was then repeated, with the exception that rats received a larger portion (35 kJ)
      of the test meal. The postprandial increase in oxygen consumption was measured
      for 30 min after the small meal and 90-180 min after the completion of the large
      meal. The measurements were made in saline-injected and propranolol-injected
      rats. ED rats exhibited hyperphagia as well as an increase of 32% in resting
      metabolic rate after a 16 h fast. The sympathetically-mediated postprandial
      increase in oxygen consumption was greater after an energy dense meal than after
      a control meal in CD rats, and was higher in ED rats than in CD rats fed an
      energy dense meal. It was concluded that the sympathetically-mediated increase in
      the thermogenic response to food, as well as the increase in fasting metabolic
      rate can help prevent obesity development in hyperphagic rats.

PMID- 7735346
TI  - Hyperuricaemia: relationships to body fat distribution and other components of
      the insulin resistance syndrome in 38-year-old healthy men and women.
AB  - The aim of this work was to evaluate whether hyperuricaemia correlates with the
      cluster of metabolic and haemodynamic disorders closely associated with insulin
      resistance syndrome (IRS) in young apparently healthy individuals also, and, if
      so, whether hyperinsulinaemia itself or some other component of this syndrome,
      are independently associated with hyperuricaemia. The subjects were a random
      population sample of 181 (M = 94/F = 87) 38-year-old apparently healthy subjects,
      non-diabetic, without a history of gout. Obesity (overall and regional), serum
      lipid profile, uric acid, fasting glucose and insulin, 2 h insulin after glucose
      load (only in men), blood pressure and main behavioural variables were measured.
      As expected, most parameters were statistically different between men and women.
      In particular, serum uric acid levels were significantly higher in the male group
      than in female group (348 +/- 59 mumol l-1 vs 277 +/- 59 mumol l-1, P < 0.0001).
      After adjustment for sex, in pooled individuals, serum uric acid concentration
      showed positive associations with BMI (r = 0.21; P < 0.001), waist/hip girth
      (WHR; r = 0.45; P < 0.0001), waist/thigh girth (WTR; r = 0.35; P < 0.0001) and
      subscapula/triceps skinfold ratios (STR; r = 0.30; P < 0.001). Furthermore, serum
      uric acid was also positively correlated with fasting insulin (r = 0.23; P <
      0.001), serum triglycerides (r = 0.34; P < 0.0001), LDL cholesterol (r = 0.16; P
      = < 0.01), diastolic blood pressure (r = 0.26; P < 0.001), and negatively with
      HDL/total cholesterol ratio (r = 0.28; P < 0.001).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7735347
TI  - Different genes for obesity are associated with insulin loss of regulation of the
      membrane (Ca2+ + Mg2+)-ATPase in the obesity syndrome. Lessons from animal
      models.
AB  - Intracellular Ca2+ homeostasis is impaired in tissues from obese humans and rats
      and insulin loses its regulatory effect on the plasma membrane (Ca2+ + Mg2+)
      ATPase in kidney basolateral membranes (BLM) from the genetically obese fa/fa
      rats. We have demonstrated that loss of insulin regulation of the ATPase may
      impair insulin biologic effects and may therefore contribute to the insulin
      resistance in the obese rodents. To test whether the defect is restricted to one
      species or to one gene of obesity, studies were extended to an additional
      genetically obese rodent of another species the C57BL/6J ob/ob mice. Twelve-weeks
      old obese and control male mice were used and (Ca2+ + Mg2+)-ATPase activity and
      its regulation by insulin were evaluated in their kidney BLM. The obese mice were
      heavier (56.4 +/- 2.5 vs 30.5 +/- 1.2 g P < 0.05), were hyperinsulinemic (6.32 +/
      1.87 vs 0.59 +/- 0.13 ng/ml P < 0.05) and had decreased (by 80%) specific
      binding of insulin to their epididymal fat cells compared with their non-obese
      littermates controls (ob/+, +/+). Yet, non-fasting plasma glucose levels were
      similar in the obese and control mice (227.0 +/- 19.3 vs 226.8 +/- 13.7 mg/dl
      N.S.). Basal activity of the (Ca2+ + Mg2+)-ATPase was similar in membranes from
      the ob/ob and control mice. However, while insulin (1-40 ng/ml) stimulated the
      ATPase activity in BLM form controls in a dose dependent manner (15-52%), no
      effect of insulin on the enzyme was seen in BLM from the obese mice even in the
      presence of the highest (40 ng/ml) concentration of insulin.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7735348
TI  - Pneumococcal bacteraemia and meningitis in England and Wales 1982 to 1992.
AB  - In the 11 years from 1982 to 1992, microbiology laboratories in England and Wales
      reported 22,567 episodes of serious illness in which Streptococcus pneumoniae was
      isolated from blood and 3500 in which it was isolated from cerebrospinal fluid.
      Half of the reported cases of bacteraemia occurred in people of over 65 years
      (11,299 cases). A predisposing cause was seldom reported. Annual totals of
      reports of pneumococcal bacteraemia and meningitis have risen in parallel with
      other serious infections. The rates of pneumococcal infections reported in very
      young and elderly people have risen much more rapidly and, although this
      observation may be artefactual, it may be associated with an observed increase in
      reports of antibiotic resistance. The proportion of pneumococcal isolates
      resistant to penicillin rose from 0.3% in 1989 to 1.9% in 1992 (p < 0.05). We
      suggest that the role of pneumococcal vaccination should be re-evaluated.

PMID- 7735349
TI  - COVER (cover of vaccination evaluated rapidly): 33.

PMID- 7735350
TI  - Will London's COVER meet the target?

PMID- 7735351
TI  - Active surveillance of health and safety in microbiology laboratories.
AB  - In microbiology laboratories highly infectious material is handled alongside
      complex and potentially dangerous equipment, and staff are therefore at risk of
      infections and accidents. Acts of parliament and regulations exist to protect
      staff in the workplace, including those exposed to biological agents. The current
      monitoring of health and safety in laboratories seeks to ensure that employers
      and employees comply with existing regulations, but this form of passive
      surveillance is of limited value because it does not highlight shortcomings in
      techniques, equipment, premises, or personnel. We propose a scheme for the
      surveillance of health and safety in microbiology laboratories that will actively
      seek information about laboratory incidents and practices, in order to enable
      appropriate preventive measures to be instituted.

PMID- 7735352
TI  - Brucella melitensis: an unexpected isolate from cerebrospinal fluid.
AB  - A specimen of cerebrospinal fluid was initially handled with 'category 3'
      precautions because the patient came from Somalia, where tuberculosis and HIV
      infection are endemic. An isolate from the specimen, initially thought to be a
      Neisseria species, was subsequently handled on the open bench. It was later
      identified as Brucella melitensis. Laboratory procedures should allow for the
      possibility of brucella in such specimens until a positive identification has
      been made.

PMID- 7735353
TI  - How big a sample do you need for the power you want?

PMID- 7735354
TI  - Malaria prophylaxis for travellers from Britain.

PMID- 7735355
TI  - Sexually transmitted diseases quarterly report: gonorrhoea in England and Wales.

PMID- 7735356
TI  - Hospital infection control: revised guidance.

PMID- 7735357
TI  - Relation of intracorporal pressure and end-diastolic velocity during duplex
      Doppler sonography in the evaluation of veno-occlusive dysfunction.
AB  - In 37 patients 25 to 69 years old (mean age 49.6 years) with suspected
      'vasculogenic erectile dysfunction', diagnosed on the basis of repeated negative
      reactions to intracavernous pharmacological stimulation, duplex Doppler
      measurements and pharmacocavernosometry were performed in one session under
      simultaneous pressure registration. A statistically significant difference
      between patients with and without veno-occlusive dysfunction was found by
      combining end-diastolic velocity and pressure in time. We conclude that color
      Doppler scanning in combination with simultaneous pressure registration can
      predict veno-occlusive dysfunction in 83-95% of the patients.

PMID- 7735358
TI  - A new approach to the pharmacologic treatment of impotence.
AB  - A new approach to the use of topical medications to induce penile erections is
      suggested. Many impotent patients treat erectile dysfunction with injected
      vasoactive drugs like papaverine, phentolamine and PGE-1. However, many patients
      fear using needles and the possible side effects from injections are well known
      (pain, ecchymosis, priapism, fibrosis of corpora cavernosa). In six patients with
      erectile impotence who sought an alternative to pharmacologic injection therapy,
      a 1 cm square window was created in Buck's fascia and tunica albuginea and
      covered with a piece of the deep dorsal vein of the penis. The penile skin
      overlying the window was marked with India ink and vasoactive medication was
      applied to this area. The goal of this procedure was to enable the topical
      erection-inducing medication to pass through the skin of the penis, through the
      window and into the corpus. All of the patients experienced a satisfactory
      erectile response after application of nitroglycerin cream as documented by
      penile Doppler ultrasound evaluation. Two of the six patients currently use only
      the nitroglycerin cream to induce erections satisfactory for sexual intercourse.
      Three patients alternate the use of the cream and injections. One patient prefers
      injection. This procedure may offer a desirable alternative to injection therapy
      for selected patients with impotence.

PMID- 7735359
TI  - Experience with the long-term effect of microsurgical penile revascularization.
AB  - Fourty-two consecutive men underwent microsurgical penile revascularization for
      arterial insufficiency at least one year prior to this review. Data on the
      results of surgery were collected by questionnaire or telephone in 33 men (79%)
      with complete follow-up and by chart review in 9 men (21%) with partial follow
      up. Success was measured as the ability to achieve successful intercourse on the
      majority of attempts without adjuvant therapy. Successful results are as follows:
      19/36 (53%) at one year; 13/32 (41%) at two years; 14/26 (54%) at three years;
      9/15 (56%) at four years; 4/10 (40%) at five years. Eight of 9 patients with
      partial follow-up functioned at last contact. Failures tended to occur early and
      successes appeared to remain stable over the time period studied. This long-term
      success rate speaks to a true benefit, and not a placebo effect, of penile
      revascularization in treating arteriogenic impotence.

PMID- 7735360
TI  - The use of vibrotactile stimulation for determining sexual potency in the
      laboratory in men with erectile problems: methodological considerations.
AB  - Vibrotactile stimulation, when used in combination with visual sexual
      stimulation, has been shown to enhance erectile response in sexually functional
      men. The present study attempted to describe a diagnostic methodology, including
      the development and application of a new mini-vibrator, that might enhance penile
      response in men with erection problems. Tests on 78 men with either erectile
      dysfunction (ED), or a combination of erectile dysfunction and premature
      ejaculation (ED+PE), showed that vibratory stimulation together with an erotic
      video (EV+VT), produced greater penile response than the erotic video alone (EV).
      The new mini-vibrator was more effective than a previously used model, and
      produced clinically significant increases in erectile response in ED+PE men. In
      addition, the enhancing effect of the combined stimulation on self-reported
      penile response was greater when it followed EV than when it preceded it. The use
      of vibrotactile stimulation and visual sexual stimulation together may therefore
      assist in determining the potential sexual potency of men experiencing erection
      problems during the process of differential diagnosis.

PMID- 7735361
TI  - Some mythologic, religious, and cultural aspects of impotence before the present
      modern era.
AB  - Impotence is not only a problem of modern society. Centuries ago man has sought
      for causes and remedies for impotence, originally looking much more outside
      himself rather than within himself. This article reviews and reflects on
      mythological, religious and cultural aspects of impotence, especially before the
      beginning of the 18th century.

PMID- 7735362
TI  - Reasons for high drop-out rate with self-injection therapy for impotence.
AB  - One hundred and eighty patients, average age of 58 years (range 24-75) were
      evaluated for impotence and were advised to undergo pharmacologic self-injection
      therapy with either papaverine/Regitine (90%) or prostaglandin E1 (10%). Follow
      up was available from 2 months to 3 years (average 11 months). The cause of
      impotence was determined by hormonal testing, Rigiscan and psychological testing.
      The etiology of impotence was organic (70%), psychogenic (20%), and mixed (10%).
      After the initial test injection 22% of patients did not enroll in the self
      injection program or were lost to follow-up. The group with psychogenic impotence
      had the highest satisfaction/usage rate at 42%. Overall only 20% of patients were
      satisfied long-term and were actively using self-injection therapy. Of the 140
      patients available for follow-up, 112 patients (80%) discontinued self-injection
      therapy. The reasons for discontinued usage were alternate treatment (prosthesis
      or vacuum device) 15%, return or improvement of erections 8%, partner
      dissatisfaction or loss of partner 10%, or complications of injection therapy
      10%. Cost was not a factor for discontinued use. Loss of interest caused 57% of
      patients to stop using self-injection therapy. Although pharmacologic self
      injection therapy is initially promising there is a high drop-out rate at long
      term follow-up.

PMID- 7735363
TI  - Consensus and progress in corpus cavernosum-EMG (CC-EMG).

PMID- 7735364
TI  - Steroid hormone receptors: activators of gene transcription.
AB  - Over the past three decades, a great deal of evidence has accumulated in favor of
      the hypothesis that steroid hormones act via regulation of gene expression. The
      action is mediated by specific nuclear receptor proteins, which belong to a
      superfamily of ligand-modulated transcription factors that regulate homeostasis,
      reproduction, development and differentiation. This family includes receptors for
      steroid hormones, thyroid hormones, hormonal forms of vitamin A and D,
      peroxisomal activators, and ecdysone. Molecular cloning and structure/function
      analyses have revealed that all members of the steroid/thyroid hormone/retinoic
      acid receptor family have a similar functional domain structure: a variable N
      terminal region, which is involved in modulation of gene expression; a short well
      conserved DNA-binding domain, which is crucial for recognition of specific DNA
      sequences and for receptor dimerization; and a partially conserved C-terminal
      ligand-binding domain, which is important for hormone binding and also for
      receptor dimerization and transactivation. In contrast to other members of the
      receptor superfamily steroid hormone receptors form transient complexes with
      several heat shock proteins. This interaction promotes proper folding and
      stability of the receptor molecule. Hormone binding induces a conformational
      change in the receptor molecule and simultaneously a dissociation of all heat
      shock proteins, which results in DNA-binding of the hormone-receptor
      complex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735365
TI  - Growth hormone (GH)-deficiency in adults: clinical features and effects of GH
      substitution.

PMID- 7735366
TI  - Epidermal growth factor receptor and human fetoplacental development.
AB  - Alteration of placental development directly interferes with fetal growth.
      Epidermal growth factor (EGF) plays a major role in placental implantation,
      growth and differentiation. EGF acts on its placental target cells, i.e. the
      trophoblasts, via a specific receptor (EGFR) which belongs to the tyrosine kinase
      receptor family. Abundant placental EGF receptors are located in the brush border
      at the fetomaternal interface. EGFR expression is modulated by trophoblast
      differentiation and by hormones or toxic substances such as smoke. Interestingly,
      in microvilli purified from placentae of infants with intrauterine growth
      retardation (IUGR) a decrease or absence of tyrosine kinase activity is observed.
      This suggests that an alteration of EGFR biological activity might interfere with
      the fetoplacental unit development.

PMID- 7735367
TI  - Long-term therapy with a single daily subcutaneous dose of growth hormone
      releasing hormone (1-29) in prepubertal growth hormone deficient children.
      Venezuelan Collaborative Study Group.
AB  - As part of a multicenter study to evaluate the efficacy and safety of one daily
      subcutaneous dose of 30 micrograms/kg of GHRH, 16 prepubertal GH-deficient
      children with a mean chronological age of 9.0 +/- 2.3 years were treated for 12
      to 24 months. After six months of therapy 11 children (68.7%) were considered
      good responders in that their growth velocity increased by greater than 2 cm/yr
      over baseline and were continued on GHRH, while five subjects (31.3%) were
      regarded as poor responders and switched to recombinant hGH for the following six
      months. Growth velocity increased significantly in responders from a baseline of
      3.4 +/- 0.7 cm/yr (mean +/- SD) to 6.8 +/- 0.1 cm/yr, 6.2 +/- 0.9 cm/yr, 6.6 +/-
      1.0 cm/yr and 6.5 +/- 0.7 cm/yr at 6, 12, 18 and 24 months respectively. Bone
      ages advanced by an amount equivalent to the months of treatment. GHRH antibodies
      were detected in 4/11 and 6/11 responders at six and 12 months of treatment and
      in 2/5 non-responders at six months, but seemed not to interfere with growth. No
      side effects or changes in glucose and lipid levels were noted during therapy.
      These results suggest that GHRH (1-29) at the dose and schedule used is generally
      effective in the treatment of GH deficiency.

PMID- 7735368
TI  - Priming with GHRH (1-29) NH2: an aid in differential diagnosis between
      hypothalamic and pituitary deficiencies.
AB  - More than 80% of children with growth hormone deficiency (GHD) respond with a
      rise in growth hormone levels when given 1 microgram/kg body weight of growth
      hormone-releasing hormone (GHRH) in an i.v. bolus. We conducted a study to
      determine whether the failure of the remaining 20% to respond to GHRH is due to a
      pituitary deficiency or a secondary effect associated with chronically
      understimulated somatotrophs. We administered GHRH to "prime" 16 short-statured
      children (> 2 SD) presenting delayed growth (< 4 cm/year), who had not responded
      initially when given a single dose of GHRH. Priming consisted of administering
      GHRH (1-29) NH2 (5 micrograms/kg body weight, s.c.) for six consecutive days.
      Plasma GH response was studied again after an i.v. injection of 1 microgram/kg
      body weight of GHRH (1-29) NH2 on the seventh morning. On the basis of these
      results we were able to separate our patients into two groups: a) responders to
      priming (n = 8), whose GH responses to pharmacological and acute GHRH tests were
      < 10 ng/ml, with a 12-hour sleep secretion < 3 ng/ml/min. Priming increased the
      plasma GH response to acute GHRH in all the children in this group (6.0 +/- 2.1
      ng/ml to 18.0 +/- 5.4 ng/ml; p < 0.001); b) non-responders to priming (n = 8),
      whose GH responses to pharmacological and acute GHRH tests were also < 10 ng/ml,
      with 12-hour sleep secretion < 3 ng/ml/min, but in whom priming with GH did not
      increase the plasma GH response (5.5 +/- 2.8 ng/ml to 6.2 +/- 2.9 ng/ml; p =
      NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735369
TI  - The new highly sensitive adrenocorticotropin assay improves detection of patients
      with partial adrenocorticotropin deficiency in a short-term metyrapone test.
AB  - This study was designed to evaluate a short term metyrapone test using a highly
      sensitive (HS) IRMA ACTH assay and to evaluate the usefulness of a morning ACTH
      level as a screening test for partial ACTH deficiency. ACTH, 11-deoxycortisol and
      cortisol levels were evaluated over four hours in the morning after a single 40
      mg/kg oral dose of metyrapone was administered at 0800 hours. 26 control children
      and 32 possibly pituitary deficient patients were evaluated. Based on 11
      deoxycortisol levels alone, 17 of the patients passed the test, 11 patients
      failed the test and the result was inconclusive in four patients (12.5%).
      Evaluation of the increase in ACTH levels (delta ACTH) following metyrapone
      identified three of the above four with partial ACTH deficiency. The delta ACTH
      was consistent with the 11-deoxycortisol results in the remainder of patients.
      There was no difference in morning ACTH levels between controls and patients with
      partial ACTH deficiency. The measurement of ACTH using the HS IRMA assay,
      increases the sensitivity of the metyrapone test in detecting patients with
      partial ACTH deficiency. This test may be used safely in pediatric patients on a
      repetitive basis, especially in those children who may have progressive ACTH
      failure following hypothalamic-pituitary irradiation.

PMID- 7735370
TI  - The role of TRH-stimulated prolactin responses in distinguishing gonadotropin
      deficiency from constitutional delayed puberty.
AB  - LHRH and TRH tests were performed in 16 boys age 14.5-18.5 years with
      constitutional delayed puberty (CDP); 9 idiopathic hypogonadotropic hypogonadism
      (IHH) males, age 15.0-22.0 years; and 7 control subjects age 14.5-19.5 years. The
      responses of FSH and LH to LHRH stimulation overlapped so that it was difficult
      to differentiate IHH from CDP. Some patients with IHH had normal gonadotropin
      responses. Basal PRL levels were in the normal range in control, IHH, and CDP
      patients. We found a 6 to 25 times increment or a response of more than 22 ng/ml
      (normal response) with respect to basal levels in the control group. In the CDP
      group, we found 2 to 19 fold increments in basal PRL levels after TRH stimulation
      and the maximum response was more than 22 ng/ml in all the patients. In the IHH
      group, the increment in basal PRL levels was 2-9 times more after the TRH test
      and the maximum PRL response was more than 22 ng/ml in 6 of the 9 patients.
      Although the mean peak responses of PRL to TRH were significantly lower in the
      IHH group compared to CDP and controls (p < 0.001), the mean peak individual
      responses in all groups were in the normal range (minimum 2-fold increment) and
      the responses were more than 22 ng/ml in all cases except 3 of 9 patients in the
      IHH group. We conclude that PRL response to TRH may help in differentiating CDP
      from IHH if a "cut off" response level of 22 ng/ml is used.

PMID- 7735371
TI  - A randomized trial of a somatostatin analog for preserving beta cell function in
      children with insulin dependent diabetes mellitus.
AB  - In an attempt to rest the beta cells of newly diagnosed children with type I
      diabetes mellitus (IDDM) and thus possibly preserve beta cell function, ten
      children were given Octreotide, a somatostatin analog, for the first 21 days
      after diagnosis. Ten age-matched diabetic children served as controls. Although
      there were no differences in either insulin requirements or in hemoglobin A1
      levels, there were significant increases in the glucagon-stimulated C-peptide
      levels of the experimental group at six and 12 months after diagnosis, compared
      to control patients.

PMID- 7735372
TI  - Both glucagon excess and insulin deficiency characterize maturity-onset diabetes
      mellitus of youth (MODY).

PMID- 7735373
TI  - Thyroid function and serum IGF-1 in children before and after liver
      transplantation.
AB  - We report results of serum thyroid hormone and IGF-1 concentrations in 20
      children, 1.2 to 13.6 years old, with various degrees of chronic liver
      dysfunction (CLD), before and after successful orthotopic liver transplantation
      (OLT). Ten children presented with moderate chronic liver disease (CLD-M) with
      prothrombin time (PT) > 50% and serum albumin concentration > 3 g/dl; 7 children
      had severe chronic liver disease (CLD-S) with PT < 50% and serum albumin
      concentration < 3 g/dl; and 7 children who had received an OLT, who had normal
      liver function at the time of the study. Four of the latter group were also
      studied before OLT. Patients with CLD-M had normal mean +/- SD serum levels of
      total T3 (2.0 +/- 0.7 nmol/l), total T4 (125 +/- 25.9 nmol/l) and fT4
      concentrations (16 +/- 2.8 pmol/l). In contrast, children with CLD-S showed a
      significant decrease in thyroid hormones together with normal basal TSH values
      (T3 0.8 +/- 0.0 nmol/l; T4 45.6 +/- 19.5 nmol/l; fT4 7.4 +/- 1.1 pmol/l; TSH 3.8
      +/- 0.9 mU/l). Patients who received a successful OLT showed mean peripheral
      thyroid hormone concentrations significantly higher than CLD-S patients (T3 1.7
      +/- 0.7 nmol/l, p < 0.005; T4 92.8 +/- 18.2 nmol/l, p < 0.001; fT4 14.5 +/- 3.1
      pmol/l, p < 0.001). A significant correlation was found between thyroid hormone
      levels and PT or serum albumin. In the nine patients with CLD-M and CLD-S in whom
      serum IGF-1 concentration was measured, values found (mean +/- SD 0.08 +/- 0.05
      U/ml) were below the 95% confidence limit of matched controls.

PMID- 7735374
TI  - HLA haplotypes and hormonal studies in 25 Italian families of patients with
      classical and non-classical 21-OH deficiency.
AB  - To investigate the genetic polymorphisms of the HLA region and the molecular
      defect of the P450c21B gene in congenital adrenal hyperplasia (CAH) due to 21
      hydroxylase deficiency, we studied 89 individuals from 25 families of CAH
      patients (14 classical forms, 11 non-classical forms). The following
      immunogenetic and hormonal investigations were performed: HLA-A and B typing,
      restriction fragment length polymorphism (RFLP) analysis of 21-hydroxylase A and
      B genes, and serum 17-OH-progesterone values determined basally and 60 min after
      ACTH stimulation. In the patients affected by the classical form, RFLP analysis
      revealed 5 deletions and 1 gene conversion in 6 haplotypes and no molecular
      defect in the others, who probably carry point mutations. In the patients with
      non-classical form we found P450c21A duplication in 11/18 haplotypes; 9 of the 11
      patients shared the HLA-B14 allele. Utilizing both hormonal and genetic data we
      identified two cryptic forms; hormonal data alone failed to differentiate
      heterozygous from normal individuals.

PMID- 7735375
TI  - Hypothalamic dysfunction at ideal body weight simulating anorexia nervosa.
AB  - Hypothalamic dysfunction is common in patients with anorexia nervosa, but
      typically follows reductions of body weight to well below ideal body weight. We
      report a patient with hypothalamic dysfunction accompanying volitional weight
      reduction, whose body weight never fell below ideal body weight and whose
      hypothalamic function improved following weight gain. These observations suggest
      that the "set point" for normal hypothalamic function may exceed ideal body
      weight in some patients. In addition, hypothalamic dysfunction may persist for
      months following weight gain and the resumption of menses.

PMID- 7735376
TI  - True precocious puberty associated with phenylketonuria.
AB  - We studied a girl with phenylketonuria who demonstrated signs of precocious
      puberty. At the age of 7.5 years she had premature telarche. Her height age was 7
      9/12 years and her bone age was 9 years. Gonadotropin responses to LHRH
      administration were consistent with central precocious puberty. Elevated serum
      phenylalanine levels in this patient, due to poor compliance with the
      phenylalanine restricted diet, may be related to the early onset of puberty.

PMID- 7735377
TI  - A case of Laron syndrome diagnosed in Slovenia.
AB  - We report the first case of Laron syndrome (LS) diagnosed in Slovenia. The boy, a
      product of non-consanguineous Slovenian parents of normal height, presented with
      slow growth and motor development since birth. At age 4 and 6 years, he had all
      the characteristic signs of LS, identical to those in growth hormone deficiency
      (GHD). Laboratory tests showed hypoglycemia, markedly elevated plasma hGH, low
      serum insulin-like growth factor-1 (IGF-1) with no rise after exogenous hGH, and
      low serum growth hormone binding protein (GHBP). A sister of the maternal
      grandfather is short (145 cm) and was found to have below normal serum GHBP,
      findings compatible with heterozygocity for this disorder.

PMID- 7735378
TI  - Amyloid goiter in a child with familial Mediterranean fever.
AB  - A 7 year-old Turkish boy presented with a euthyroid goiter, which was noted
      during evaluation of familial Mediterranean fever. Amyloid deposits in the
      thyroid were found on fine-needle aspiration biopsy. Slight involution of the
      goiter within seven months may be attributed either to colchicine therapy or to
      treatment with levothyroxine and iodide.

PMID- 7735379
TI  - Hirschsprung's disease associated with isolated familial medullary carcinoma of
      the thyroid.
AB  - We present two siblings with neonatal Hirschsprung's disease in whom isolated
      familial medullary carcinoma of the thyroid was diagnosed at the age of 16 and 19
      years. Rectal biopsy in each patient revealed total absence of ganglion cells in
      the myenteric plexus and hypertrophied nerve fibers characteristic of
      Hirschsprung's disease. Both underwent total thyroidectomy and histological
      examination revealed bilateral and multifocal medullary carcinoma of the thyroid.
      These two patients belong to a large family in whom another 12 affected members
      with medullary carcinoma of the thyroid were found. Our description is the first
      report of an association between Hirschsprung's disease and isolated familial
      medullary carcinoma of the thyroid. We suggest that familial occurrence of
      Hirschsprung's disease could be an early presentation of familial medullary
      carcinoma of the thyroid either as the isolated form or as part of multiple
      endocrine neoplasia type IIa or IIb.

PMID- 7735380
TI  - Implementing CQI on a budget: a small hospital's story.
AB  - BACKGROUND: The need to move toward continuous quality improvement (CQI) is often
      perceived as a financial hardship on large and small hospitals alike. Avista
      Hospital, a small, 50-bed hospital, accepted the challenge to implement CQI in a
      thorough but cost-effective manner. METHOD: Without the use of consultants, the
      CQI process was developed internally using formal and informal methods of
      education for the change agents, and just-in-time education for improvement
      teams. All employees were involved in a brainstorming session to introduce them
      to the concept of CQI and to define quality and identify customers. The
      implementation plan was established on a five-year timeline to provide a
      methodical and systematic approach, and the entire process was under the
      direction of a quality council. ROUNDTABLES: To date 18 RoundTables have been
      chartered by the quality council. One RoundTable, "The Care of the MI [myocardial
      infarction] Patient," addressed the lack of continuity in the teaching of the MI
      patient. The team developed a teaching plan, with all printed materials provided
      in a binder to patients. CONCLUSIONS: The overall cost to implement the five-year
      plan, including education, staff time, and a budgeted amount to begin recognition
      celebrations in 1995, was estimated at $10,000. Commitment and determination are
      the necessary components for implementation of a CQI program. With proper
      planning and support from the administration, a small hospital can be successful
      at CQI.

PMID- 7735381
TI  - Think globally, act locally: an approach to implementation of clinical practice
      guidelines.
AB  - BACKGROUND: In an environment of concern about the rising costs of medical care,
      the Vermont Program for Quality in Health Care (VPQHC; the program) was
      incorporated in 1988 as a nonprofit organization and in 1989 was made a peer
      review organization by the state legislature. The program acts a resource center
      for health care in Vermont, coordinating three functions: implementation and
      maintenance of a statewide database for healthcare quality; training for health
      care providers in continuous quality improvement (CQI) methods and support for
      their CQI projects; and focusing clinical study group work on specific diagnoses
      or procedures. METHODS: The program uses a seven-step process for implementing
      CQI: pick a process (modify a nationally developed guideline or develop a new
      guideline); select a team of people involved in doing the work; establish goals
      and key quality factors; document the clinical process; determine what and how to
      measure; measure and analyze data; and modify the process to improve. GUIDELINE:
      This article describes the implementation of a guideline from the American
      College of Obstetricians and Gynecologists (ACOG) on cesarean section (C
      section). Except for a few specific contraindications, the ACOG paper states that
      it is reasonable to encourage vaginal birth after C-section. A related set of
      criteria from ACOG states that the benchmark for emergency C-section should be 30
      minutes from the decision to proceed with an emergency C-section until the baby
      is born. CASE STUDY: State C-section rates from 1985-1990 showed wide variation
      by hospital. Such wide variation is based as much on practice style as on sound
      science. C-section rates (primary and repeated) were measured, plotted, and
      shared with Vermont hospitals. Successful vaginal birth after C-section (VBAC)
      rates from the statewide data-base also were shared. Based on these data, one
      hospital, Hospital A, developed a plan to lower its repeated C-section rate and
      improve its VBAC rate. Hospital A collected and reviewed local data, which showed
      interesting variations. The time from decision to birth became the focus of the
      overall project; Hospital A designed its project to study events during the time
      from decision to birth. RESULTS: Most recent data (1992-1993) from Hospital A
      shows improvement in three areas. First, 89% of patients having emergency C
      sections met the goal of a 30-minute time frame from decision to incision.
      Second, the VBAC success rate for the same time period increased to 85.7% from
      69% in the previous year, and from a mere 7% before the implementation of the
      project. Third, the percentage of total C-sections that were repeat C-sections
      fell to 36% from a high of 51%. In a follow-up evaluation, one-third of the C
      section performed from October 1, 1993, to July 31, 1994 were performed because
      of patient refusal to attempt VBAC, suggesting that there is a communitywide
      culture that influences behavior. A major effort at patient education on VBAC is
      underway. CONCLUSIONS: Think globally, act locally, might be the motto for the
      program. Implementing guidelines starts with obtaining national guidelines and
      literature but needs the use of local data to sharpen the focus on narrow areas
      to address. Specifically, it is unrealistic to tackle the entire problem at once.
      Success comes from finding specific opportunities for improvement.

PMID- 7735382
TI  - Using patient input in a cycle for performance improvement.
AB  - BACKGROUND: To effectively use patient input to improve performance, an
      organization needs a systematic method for gathering, assessing, and using those
      data to improve old processes and design new ones. This method should include the
      stages in the Joint Commission on Accreditation of Healthcare Organization's
      cycle for improving performance. It is important to remember that using patient
      input to improve performance is not an isolated activity but should be linked, in
      the organization's strategic plan as well as in its practice, to organizationwide
      efforts to improve performance. DESIGN: Designing a process to use patient input
      in performance improvement requires reviewing the patient groups served by the
      organization, the important clinical and organizational functions that affect
      patients, the dimensions of performance that affect patients in each function,
      and the possible methods for gathering and using patient input. MEASURE: The
      measurement method varies depending on the process, patient group, diagnosis, or
      other subject being measured. Any plan for measurement, including one for
      gathering patient input, should address the following questions: What data will
      be collected? Who will be involved in the collection? When, where, and how will
      the data be collected? ASSESS: Raw data cannot be the basis for improving
      performance but must be carefully assessed to provide information about current
      performance, identify opportunities for improvement, help set priorities, and
      help identify root causes of problems that can lead to improvement. IMPROVE:
      Whether using patient input to design a new process or to redesign an existing
      process, the goal is to translate patient input into specific characteristics
      (key quality characteristics) that can be addressed by the improvement plan. Once
      a new or redesigned process has been implemented, teams must measure its effect.
      This measurement often involves going back to patients and collecting feedback to
      see if the process is meeting their needs and expectations, usually through a
      written or telephone survey. To develop an instrument to measure satisfaction,
      staff can return to the specifications and indicators they developed based on
      patients needs and expectations.

PMID- 7735383
TI  - Does occupational exposure to dust prevent colorectal cancer?
AB  - OBJECTIVES: To explore the impression that occupational epidemiologists tend to
      focus on associations suggestive of increased risk and tend to ignore those
      associations in which risk is not increased. To examine the risk of colorectal
      cancer in cohorts exposed to dust, cohorts in which it has been suggested that
      occupational exposure is a cause of increased risk of stomach cancer. METHODS: A
      review of the publications in the English language on mortality among hard rock
      miners, granite, and quarry workers identified from a MEDLINE search and the
      index of the library of the Ontario Ministry of Labour. RESULTS: When all of the
      studies were combined, there were significant excesses of lung and stomach
      cancers, but a significant deficit of colorectal cancer (standardised mortality
      ratio (SMR) = 83.9; 95% confidence interval (95% CI) 76-91). Overall mortality
      from gastrointestinal cancer was close to expectation (SMR = 105; 95% CI 99-111).
      Among those cohorts with increased risk of stomach cancer, rates of colorectal
      cancer were significantly decreased (SMR = 80; 95% CI 72-88). Among cohorts
      without increased risk of stomach cancer, the SMR for colorectal cancer was not
      significantly different from 100 (SMR = 98; 95% CI 81-115). CONCLUSIONS: This
      review supports the impression that occupational epidemiologists tend to focus on
      associations suggestive of increased risk and tend to ignore those associations
      in which risk is not increased. The explanation for the inverse association
      between risk of stomach and colorectal cancer is uncertain and deserves further
      study.

PMID- 7735384
TI  - Mortality from lung cancer and other diseases related to smoking among fishermen
      in north east Italy.
AB  - OBJECTIVES: To study the mortality of fishermen. This was suggested by a cluster
      of cases of lung cancer in Chioggia, a large fishing harbour in the Veneto. The
      aim was to weight occupation against smoking with respect to risk of lung cancer.
      METHODS: 7530 fishermen registered in the 1971-86 port authority registers of
      Chioggia and Venice were followed up for mortality from 1971 to 1989. Of 475
      causes of death, 460 were traced. Standardised mortality ratio (SMR) was
      calculated with the regional population as a reference. A nested case-control
      study was carried out in Chioggia decedents only by interviewing next of kin.
      Complete data were obtained in 172 (70% response). Cases (lung cancer deaths) and
      controls (other causes of death) were compared for smoking and occupation, as a
      group of non-fishermen was available in the cohort. Logistic regression analysis
      was used to adjust for confounding factors. RESULTS: SMRs were high for lung
      cancer but low for other diseases related to smoking: circulatory and respiratory
      disease, tumours of the mouth, pharynx, oesophagus, and bladder. Likewise, SMRs
      were high for liver cancer but low for other diseases related to alcohol:
      digestive and circulatory disease, buccal, pharyngeal, and oesophageal tumours.
      In the case-control study, the risk of lung cancer was found to be related to
      smoking, and there was no interaction between occupation and smoking. When
      adjusted for age and smoking, the occupational indicators had no influence on the
      risk of mortality from lung cancer. CONCLUSIONS: Among fishermen in north east
      Italy the greatest health hazard is lung cancer, and the factor involved in this
      risk is smoking, not occupation. Smoking, however, was linked with long hours at
      sea in another study.

PMID- 7735385
TI  - Cancer incidence in Swedish sterilant workers exposed to ethylene oxide.
AB  - OBJECTIVES: To assess the risk of cancer, especially leukaemia, in a cohort of
      sterilant workers exposed to ethylene oxide (EtO). METHODS: A cohort of 2170
      workers employed for at least one year in two plants that produce disposable
      medical equipment sterilised with EtO has previously been established. The
      results of an update with four more years of observation are presented. The
      cancer incidence was assessed for the periods 1976 to 1990 and 1972 to 1990 and
      cause specific standardised incidence ratios (SIRs) were calculated. Individual
      cumulative exposure to EtO, expressed as ppm-years, was estimated and used in
      exposure-response analyses. RESULTS: Six lymphohaematopoietic tumours were
      observed (SIR 1.78, 95% confidence interval (95% CI) 0.65-3.88), of which two
      were leukaemias (SIR 2.44; 95% CI 0.30-8.81). When those with cumulative
      exposures to EtO below the median value (0.13 ppm-years) were excluded, and a
      minimum of 10 years induction latency period was applied, the incidence ratio for
      leukaemia increased further (SIR 7.14, 95% CI 0.87-25.8), but was still not
      significantly enhanced. CONCLUSIONS: The risk estimate for leukaemia increased,
      but non-significantly, with time since start of exposure, and with cumulative
      exposures to EtO above the median value. The subjects with leukaemia had,
      however, only slightly higher cumulative exposure estimates for EtO than the
      average cohort member. Nevertheless, the present results may add some minor
      evidence for an association between EtO and an increased risk of leukaemia.

PMID- 7735386
TI  - Mortality of butchers and cooks identified from the 1961 census of England and
      Wales.
AB  - OBJECTIVES: To explore a suspected hazard of lung cancer in butchers and cooks.
      METHODS: 4018 male butchers and 2062 male cooks were identified from the 1961
      census of England and Wales. 4857 (79.9%) of these men were traced through the
      National Health Service Central Register, and 3518 deaths were recorded during
      follow up to the end of 1992. Mortality from lung cancer and other causes was
      compared with that of the general population by the person-years method. RESULTS:
      Mortality from all causes was significantly below that of the national population
      in both butchers (standardized mortality ratio (SMR) 0.94, 95% confidence
      interval (95% CI) 0.90-0.98) and cooks (SMR 0.89, 95% CI 0.84-0.95). When
      allowance was made for a latency of 20 years from entry to follow up, the deficit
      in butchers was reduced, but that in cooks persisted, and was largely explained
      by a shortfall of deaths from cancer and circulatory disease. Mortality from lung
      cancer was close to expectation in the butchers (SMR 1.01, 95% CI 0.90-1.13) and
      below expectation in the cooks (SMR 0.93, 95% CI 0.75-1.13). Cooks had increased
      mortality from cancers of the oral cavity (SMR 5.57) and pharynx (SMR 2.66).
      CONCLUSIONS: The findings provide no support for an occupational hazard of lung
      cancer in either butchers or cooks. The possibility of excess risk in sub-groups
      of these occupations cannot be discounted. The high rates of oral and pharyngeal
      cancer in cooks are probably a consequence of high alcohol consumption.

PMID- 7735387
TI  - Manual handling activities and risk of low back pain in nurses.
AB  - OBJECTIVE: To investigate the risk factors for low back pain in hospital nurses,
      with particular emphasis on the role of specific nursing activities. METHODS: A
      cross sectional survey of 2405 nurses employed by a group of teaching hospitals
      was carried out. Self administered questionnaires were used to collect
      information about occupational activities, non-occupational risk factors for back
      symptoms, and history of low back pain. RESULTS: The overall response rate was
      69%. Among 1616 women, the lifetime prevalence of back pain was 60% and the one
      year period prevalence 45%. 10% had been absent from work because of back pain
      for a cumulative period exceeding four weeks. Rates in men were generally similar
      to those in women. In women back pain during the previous 12 months was weakly
      associated with height, and was significantly more common in those who reported
      frequent non-musculoskeletal symptoms such as headache and low mood. After
      adjustment for height and non-musculoskeletal symptoms, significant associations
      were found with frequency of manually moving patients around on the bed, manually
      transferring patients between bed and chair, and manually lifting patients from
      the floor. In contrast, no clear increase in risk was found in relation to
      transfer of patients with canvas and poles, manually lifting patients in and out
      of the bath, or lifting patients with mechanical aids. Confirmation of these
      findings is now being sought in a prospective study of the same population.
      CONCLUSIONS: This study confirms that low back pain is highly prevalent among
      nurses and is associated with a high level of sickness absence. People who often
      report non-musculoskeletal symptoms were significantly more likely to report low
      back pain. Specific manual handling tasks were associated with an increased risk
      of back pain; however, no such association was found with mechanised patient
      transfers.

PMID- 7735388
TI  - Sex ratios of births, mortality, and air pollution: can measuring the sex ratios
      of births help to identify health hazards from air pollution in industrial
      environments?
AB  - OBJECTIVES: To compare the sex ratios of births and mortality in 12 Scottish
      localities with residential exposure to pollution from a variety of industrial
      sources with those in 12 nearby and comparable localities without such exposure.
      METHODS: 24 localities were defined by postcode sectors. SMRs for lung cancer and
      for all causes of death and sex ratios of births were calculated for each
      locality for the years 1979-83. Log linear regression was used to assess the
      relation between exposure, sex ratios, and mortality. RESULTS: Mortalities from
      all causes were consistently and significantly higher in the residential areas
      exposed to air pollution than in the non-exposed areas. A similar, but less
      consistently significant, excess of mortality from lung cancer in the exposed
      areas was also found. The associations between exposure to the general air
      pollution and abnormal sex ratios, and between abnormal sex ratios and mortality,
      were negligible. CONCLUSIONS: Sex ratios were not consistently affected when the
      concentrations or components of the air pollution were insufficiently toxic to
      cause substantially increased death rates. Monitoring of the sex ratio does not
      provide a reliable screening measure for detecting cryptic health hazards from
      industrial air pollution in the general residential environment.

PMID- 7735389
TI  - Influence of indoor air quality and personal factors on the sick building
      syndrome (SBS) in Swedish geriatric hospitals.
AB  - OBJECTIVES: Sick building syndrome (SBS) involves symptoms such as irritation to
      the eyes, skin, and upper airways, headache, and fatigue. The relations between
      such symptoms and both personal and environmental factors were studied in 225
      female hospital workers, working in eight hospital units in the south of Sweden.
      METHODS: Symptoms of SBS and personal factors were measured by means of a
      standardised self administered questionnaire. The technical investigation
      comprised a building survey and measurements of room temperature, supply air
      temperature, air humidity, and exhaust air flow. RESULTS: The prevalence of
      symptoms differed from one unit to another. The mean value of weekly complaints
      of fatigue was 30%, of eye irritation 23%, and of dry facial skin 34%. Eye
      irritation was related to work stress, self reported exposure to static
      electricity, and was also more common in buildings with a high ventilation flow
      and a high noise level (55 dB(A)) from the ventilation system. Nasal symptoms
      were related to asthma and hay fever only. Throat symptoms were more common in
      smokers, subjects with asthma or hay fever, new buildings, and in buildings with
      a high ventilation flow. Facial skin irritation was related to a lack of control
      of the work conditions, and was more common in new buildings, and buildings with
      a high ventilation flow and ventilation noise. General symptoms, such as headache
      and fatigue, were related to current smoking, asthma or hay fever, work
      dissatisfaction, and static electricity. CONCLUSION: As the prevalence of
      symptoms was high, there is a need to improve the indoor environment as well as
      the psychosocial environment in hospitals. These improvements could include a
      reduction of ventilation noise, minimised smoking, and improvements in the
      psychosocial climate. Further research is needed to identify indoor climatic
      factors that cause the increased prevalence of symptoms of SBS in new buildings.

PMID- 7735390
TI  - Association between NAG-B and cadmium in urine with no evidence of a threshold.
AB  - OBJECTIVES: To explore the significance of the increase in urinary excretion of
      the lysosomal enzyme beta-N-acetylglucosaminidase (NAG) at low exposures to
      cadmium (Cd) that is frequently found in the absence of any other sign of renal
      dysfunction. METHODS: The activity was measured of the two main isoenzymes of NAG
      (NAG-A secreted by exocytosis and NAG-B released with cell membranes) in the
      urine of 49 male workers employed in a Cd smelter and of 20 age matched controls.
      RESULTS: An increased urinary excretion of low molecular weight proteins was
      noted only in subjects who excreted > 10 micrograms Cd/g creatinine. The urinary
      activity of NAG-B showed a dose related increase that was already significant in
      the group excreting 0.5-2 micrograms Cd/g creatinine. In multiple regression
      analysis the NAG-B activity correlated with the excretion of Cd but not with that
      of lead or mercury. The NAG-A activity was by contrast unaffected by exposure to
      Cd but correlated with the urinary excretion of lead and copper. CONCLUSIONS: As
      NAG-B is considered to be the lesional form of NAG, the existence of a specific
      association between this enzyme and urinary Cd excretion with no detectable
      threshold suggests that this metal produces cellular alterations at exposures
      commonly found in the general population.

PMID- 7735391
TI  - Mortality of inhabitants in an area polluted by cadmium: 15 year follow up.
AB  - OBJECTIVE: To assess the influence of environmental exposure to cadmium (Cd) on
      long term outcome of inhabitants living in an area polluted by Cd. METHODS: A
      follow up study for 15 years (from 1974-5 to 1991) was carried out on 2408
      inhabitants (amounting to 95% of the target population, 1079 men and 1329 women)
      of the Kakehashi River basin in Ishikawa Prefecture, Japan. These inhabitants had
      been the subjects of the health impact survey in 1974-5 to evaluate (by
      measurement of urinary retinol binding protein (RBP)) renal dysfunction induced
      by Cd. Analysis of mortality was performed by dividing subjects into a urinary
      RBP positive (> or = 4 mg/l) group and RBP negative (< 4 mg/l) group. RESULTS:
      After adjustment for age with Cox's proportional hazard model, RBP > or = 4 mg/l
      showed a significant relation to mortality in both sexes. At this time, the
      mortality risk ratio of the RBP positive to negative group was 1.71 in the men
      and 1.42 in the women. When the SMRs according to causes of deaths in the RBP
      positive group were compared with those of the RBP negative group or the overall
      Japanese population increases of SMR for cardiovascular diseases, especially
      heart failure, and renal diseases were found in both sexes. CONCLUSION: These
      results suggest that the prognosis of the exposed inhabitants with renal tubular
      dysfunction is unfavourable, and these increases of mortality are due to heart
      failure and renal diseases.

PMID- 7735392
TI  - Maintenance of stellite and tungsten carbide saw tips: respiratory health and
      exposure-response evaluations.
AB  - OBJECTIVE: To study exposure to cobalt and chromium in saw maintenance rooms and
      test respiratory health among saw filers at lumber mills. Hard-metal lung disease
      is associated with cobalt in the manufacture of tungsten carbide tools; recently
      it has also been reported among tool maintenance workers. Lumber mills often use
      saws tipped with tungsten carbide or with a newer alloy, stellite (containing
      more cobalt, as well as chromium). METHODS: A cross sectional study of 118 saw
      filers at eight lumber mills was carried out that included a standardised
      questionnaire, spirometry, personal air sampling, and examination of tasks every
      10 minutes (by observation). Comparison data were from a study of bus mechanics
      tested with similar methods. RESULTS AND CONCLUSION: Cobalt exposure was
      associated with tungsten carbide grinding but not with stellite grinding.
      Chromium exposure was associated mainly with stellite welding. Saw filers had a
      twofold increase in phlegm and wheeze (P < 0.01) and a threefold increase in
      cough, phlegm, and wheeze related to work (P < 0.001), but no increase in
      breathlessness. Stellite welding was associated with a significant increase in
      nasal symptoms and cough related to work and a small decrease in airflow (forced
      expiratory volume in one second/forced vital capacity (FEV1/FVC%), P < 0.05). Saw
      filers wet grinding with tungsten carbide had significant reductions in forced
      expiratory lung volumes (FEV1 and FVC, P < 0.05) and were significantly more
      likely to have FEV1 and FVC values in the abnormal range. Cobalt exposure (in wet
      grinding) and duration of work that involved tungsten carbide grinding were both
      associated with significant reductions in FEV1 and FVC. Average cobalt exposures
      in this study were about 5 micrograms/m3, well below the currently accepted
      permissible concentration, which suggests that the current workplace limit for
      cobalt may be too high.

PMID- 7735393
TI  - Effects within the week on forced vital capacity are correlated with long term
      changes in pulmonary function: reanalysis of studies on car painters exposed to
      isocyanate.
AB  - OBJECTIVES: To examine if car painters who work with polyurethane paints that
      contain hexamethylenediisocyanate (HDI) and hexamethylenediisocyanate biuret
      trimer (HDI-BT) develop acute as well as chronic impairment of lung function.
      METHODS: In this study data were reanalysed from two earlier studies on a group
      of car painters to see if a decrease in lung function within the week is a marker
      of vulnerability in those workers. Data on changes in forced vital capacity (FVC)
      and forced expiratory volume in one second (FEV1) within the week were available
      for 20 car painters who were also examined six years later. RESULTS: 10 men
      showed a decline in FVC within the week. There were no significant differences in
      age, duration of employment, exposures during the follow up period, or smoking
      between car painters who had decline in lung function within the week and car
      painters who had not. A significant correlation was found between the change in
      FVC within the week and the long term (six year) change in FVC, standardised for
      the effects of aging and smoking, and adjusted for the number of peak exposures.
      CONCLUSIONS: The results suggest that the decrease in FVC within the week might
      serve as a guide to identify car painters at risk of a further decrement in lung
      function above the effects of aging, smoking, and exposure.

PMID- 7735394
TI  - Significance of dermal and respiratory uptake in creosote workers: exposure to
      polycyclic aromatic hydrocarbons and urinary excretion of 1-hydroxypyrene.
AB  - OBJECTIVES: To evaluate workers' exposure in a creosote impregnation plant by
      means of ambient and biological monitoring. METHODS: Naphthalene (vapour phase)
      and 10 large molecular polycyclic aromatic hydrocarbons (PAHs) (particulate
      phase) were measured in the breathing zone air during an entire working week. 1
      Hydroxypyrene (1-HP) was measured in 24 hour urine as a metabolite of the pyrene
      found in neat (dermal exposure) and airborne creosote. RESULTS: Naphthalene (0.4
      4.2 mg/m3) showed 1000 times higher concentrations in air than did the
      particulate PAHs. In total, the geometric mean (range) of three to six ring PAHs
      was 4.8 (1.2-13.7) micrograms/m3; pyrene 0.86 (0.23-2.1) micrograms/m3, and
      benzo(a)pyrene 0.012 (0.01-0.05) micrograms/m3. There was no correlation between
      pyrene and gaseous naphthalene. The correlations between pyrene and the other
      nine particulate PAHs were strong, and gave a PAH profile that was similar in all
      air samples: r = 0.83 (three to six ring PAHs); r = 0.81 (three ring PAHs); r =
      0.78 (four to six ring PAHs). Dermal exposure was probably very high in all
      workers, because the daily output of urinary 1-HP exceeded the daily uptake of
      inhaled pyrene by < or = 50-fold. Urinary 1-HP concentrations were very high,
      even on Monday mornings, when they were at their lowest (4-22 mumol/mol
      creatinine). 1-HP seldom showed any net increase over a workshift (except on
      Monday) due to its high concentrations (16 to 120 mumol/mol creatinine) in the
      morning samples. 1-HP was always lower at the end of the shift (19 to 85
      mumol/mol creatinine) than in the evening (27 to 122), and the mean (SD) change
      over the working week (47 (18)) was greater than the change over Monday (35
      (32)). The timing of 1-HP sampling is therefore very important. CONCLUSIONS:
      Urinary 1-HP proved to be a good biomarker of exposure to three to six ring PAHs
      but not to airborne naphthalene. Hence, biomonitoring based on 1-HP has to be
      completed with exposure assessment for naphthalene as a marker for creosote
      volatiles that mainly enter the body through the lungs.

PMID- 7735395
TI  - Respiratory health of workers exposed to metal dusts and foundry fumes in a
      copper refinery.
AB  - OBJECTIVES: To assess airflow limitation in workers exposed long term to metal
      dust, the prevalence of pleural plaques in those workers exposed in the past to
      asbestos, the influence of pleural plaques on lung function, and the possible
      association with airway disease caused by asbestos. METHODS: A cross sectional
      and longitudinal (seven year) survey of 494 long term (mean (SEM) 21(1) years)
      workers in a copper refinery was carried out from medical questionnaires, chest
      radiographs, and forced spirometry. RESULTS: The prevalence of lifetime non
      smokers was 19%, current smokers 39%, and ex-smokers 42%. The prevalence of
      chronic obstructive pulmonary diseases (COPD) (forced expiratory volume in one
      second (FEV1) < 80% predicted) was 5%, small airway dysfunction (SAD) (maximal
      mid-expiratory flow (MMEF) < 60% predicted) was 7%, and this did not differ from
      the control population. The COPD and SAD were associated with cumulative smoking
      index but not with the cumulative work years at the plant or with any type of
      work at the plant. The mean (SEM) reduction of FEV1 was 20(7) ml in non-smokers,
      26(4) ml in smokers, and 26(5) ml in ex-smokers (P > 0.05). In the smokers and ex
      smokers with COPD, the loss of FEV1 was 53(10) (P < 0.02). The prevalence of
      pleural plaques was 11% (P < 0.0001); pleural plaques were found in older workers
      with known exposure to asbestos. The pleural plaques were circumscribed and
      associated with a non-significant 196 ml reduction in forced vital capacity (FVC)
      and non-significant reduction of FVC over time. The pleural plaques were not
      associated with COPD or SAD. The cumulative smoking index obtained by a
      technician did not differ from that by a chest physician. CONCLUSIONS: Despite
      exposures to asbestos that produced pleural plaques and exposures to metal dusts
      and foundry fumes the long term workers of this plant did not have excessive
      prevalence of COPD or SAD. The data suggest that low level long term exposure to
      metal dusts, gases, and foundry fumes do not necessarily cause respiratory
      dysfunction, circumscribed pleural plaques with low grades of width and extent do
      not reduce FVC significantly, and exposure to asbestos dust that produced pleural
      plaques does not necessarily produce airway dysfunction.

PMID- 7735396
TI  - Bilateral median and ulnar neuropathy at the wrist in a parquet floorer.
AB  - Many cases of work related compression neuropathy of the ulnar and median nerves
      at the wrist have been described. This report presents a case of bilateral distal
      neuropathy of the median and ulnar nerves in a parquet floorer, who laid wooden
      block flooring by hand and used the palms and volar surface of both hands to hit
      the blocks into place. He also used an electric sander and polisher. Bilateral
      numbness and paraesthesias in all fingers had been present for about one year.
      Clinical examination was normal; the neurological assessment indicated slight
      impairment in response to tactile, heat, and pain stimuli in all 10 fingers.
      Electroneurography showed increased distal motor latencies of median and ulnar
      nerves at both wrists, although the lower limbs were normal. The results of
      blood, urine, and instrumental tests excluded systemic disease or local factors
      that could cause compression neuropathy. After stopping work for three months,
      the clinical picture and electroneurographic results improved. These data support
      the hypothesis that the damage to the median and ulnar nerves had been caused by
      the patient's way of working, which provoked repeated bilateral microtrauma to
      his wrists. To diagnose work related multiple neuropathy can be difficult and an
      accurate work history is necessary. Preventive measures and diligent health care
      are required for this category of worker.

PMID- 7735397
TI  - Potential public health problems of asbestos in Jamaica.

PMID- 7735398
TI  - The effect of occupational exposure to mercury vapour on the fertility of female
      dental assistants.

PMID- 7735399
TI  - Now is the time for routine voluntary HIV testing of pregnant women.

PMID- 7735400
TI  - Pediatric human immunodeficiency virus infection. Recent evidence on the
      utilization and costs of health services.
AB  - OBJECTIVE: To measure the utilization and costs of pediatric human
      immunodeficiency virus (HIV)-related health care services. DESIGN: Cohort survey.
      SETTING: Eight outpatient departments serving large numbers of HIV-infected
      children in five standard metropolitan areas with high prevalence of HIV-infected
      children. PATIENTS: One hundred forty-one HIV-seropositive children older than 15
      months of age or children whose clinical conditions meet the definition of
      acquired immunodeficiency syndrome (AIDS) at any age who visited the selected
      providers during the second quarter of 1991. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: Quarterly interview survey (via adult proxies) of health care services
      utilization during each preceding 3-month period, repeated six times between
      March 1991 and August 1992. Charge data were abstracted from inpatient,
      outpatient, home health care, and pharmacy bills. RESULTS: Children with AIDS
      averaged 1.4 hospitalizations, 16 inpatient days, two emergency department
      visits, 18 ambulatory care visits, 15 professional home health care visits, and
      one dental visit per year, generating an estimated $37,928 in annual charges. The
      HIV-infected children used fewer services, with annual charges of $9382.
      CONCLUSIONS: We found lower utilization than reported in prior research on
      pediatric HIV and similar unit costs after inflation adjustment. Increasing
      experience in clinical management and expanded ambulatory care may have
      contributed to reductions in inpatient services utilization and total costs since
      the mid-1980s.

PMID- 7735401
TI  - Longitudinal assessment of growth in children born to mothers with human
      immunodeficiency virus infection.
AB  - OBJECTIVES: To describe and to evaluate the longitudinal growth of children born
      to mothers with human immunodeficiency virus (HIV) infection. DESIGN:
      Measurements of weight, length (measured in infants in a recumbent position) and
      height (measured in older children in an upright position), and head
      circumference were documented and evaluated longitudinally using generalized
      estimating equations in a group of children born to HIV-infected mothers.
      Children infected with HIV were compared with uninfected children and with
      National Center for Health Statistics standards. SETTING: Primary care clinic in
      an urban hospital devoted to the medical care of children born to HIV-infected
      mothers. PATIENTS: One hundred nine children born to HIV-infected mothers, 59 HIV
      infected and 50 uninfected, between birth and 70 months of age. RESULTS: The mean
      birth weights of both groups were below the 50th percentile. While the mean
      weight-for-age curve of uninfected children attained the 50th percentile by age
      24 months, the mean birth weight-for-age curve of HIV-infected children remained
      below the 50th percentile. Weight gain became significantly different between the
      two groups by age 36 months. The mean birth length-for-age curves of HIV-infected
      and uninfected children was also below the 50th percentile. The mean height-for
      age curve of uninfected children attained the 50th percentile by age 40 months,
      while that of HIV-infected children remained well below the 50th percentile.
      Linear growth between HIV-infected and uninfected children diverged earlier than
      weight, becoming significantly different by age 15 months. CONCLUSIONS: Although
      children born to HIV-infected mothers are born with weight and length below the
      50th percentile, uninfected children catch up, while HIV-infected children remain
      below the 50th percentile and experience an earlier and more pronounced decrease
      in linear growth (height-for-age) than in weight-for-age.

PMID- 7735402
TI  - Human immunodeficiency virus-specific IgA in infants born to human
      immunodeficiency virus-seropositive women.
AB  - OBJECTIVE: To determine the sensitivity and specificity of human immunodeficiency
      virus (HIV)-specific IgA for vertically transmitted HIV infection, particularly
      during the first month of life. DESIGN/SETTING/PATIENTS: Prospective cohort study
      of 140 infants born to HIV-seropositive women in a large urban teaching hospital
      and of 248 older infants and children referred for diagnosis and treatment of HIV
      infection. MAIN OUTCOME MEASURES: The HIV-specific IgA immunoblot results were
      compared with the infection status of patients as determined by Centers for
      Disease Control and Prevention (Atlanta, Ga) criteria or by sequential early
      diagnostic assays for HIV. Sensitivity, specificity, and predictive values were
      calculated for each age range. RESULTS: Among infants studied from birth, the
      rate of vertical transmission of HIV was 21.6% (25/116). The sensitivity of HIV
      specific IgA for the first month of life was 8.0% (2/25), and the specificity was
      90.1% (82/91). Sensitivity increased progressively during the first year of life,
      and the negative predictive value was 94.6% by 6 to 8 months of age. The positive
      predictive value of this assay was 18.2% for neonates but was 96% to 100% after
      the first month of life. CONCLUSIONS: False-positive test results for HIV
      specific IgA occurred with diminishing frequency during the first 4 weeks of
      life, and the frequency of detectable HIV-specific IgA was similar among the HIV
      infected and uninfected groups at this age. Beyond 1 month of age, detection of
      HIV-specific IgA is highly specific and is a useful serum-based assay for early
      diagnosis of HIV infection. These results suggest that maternal-fetal transfusion
      is common and support the hypothesis that the majority of maternal-fetal
      transmission of HIV occurs around the time of parturition.

PMID- 7735403
TI  - Street youth in Los Angeles. Profile of a group at high risk for human
      immunodeficiency virus infection.
AB  - OBJECTIVE: To characterize an urban street youth population, their self-reported
      rates of drug use, and their involvement in behaviors that put them at risk for
      infection with the human immunodeficiency virus. DESIGN: A brief structured
      interview was administered to 409 youths who had been living on the streets for 2
      or more consecutive months, or who were fully integrated into the "street
      economy." SETTING: Thirty percent of the sample were recruited from community
      based service sites and 70% were recruited from street locations and at natural
      hangouts. PARTICIPANTS: Youths were aged 12 to 23 years; 74% were male, 48% were
      ethnic minorities, 72% were homeless, 14% were gang affiliated, 20% were involved
      in drug dealing, 43% were engaged in survival sex (ie, the exchange of a sexual
      favor for money, food, a place to stay, clothes, and/or drugs), and 40% were
      homosexual or bisexual. RESULTS: Seventy percent of the youths were sexually
      active, with an average of 11.7 sexual partners (past 30 days). Youths with
      multiple sexual partners were more likely to have had a previous sexually
      transmitted disease (P < .01), to use drugs during sex (P < .001), and to be
      involved in survival sex (P < .001). Marijuana (55%), methamphetamine (62%), and
      crack (38%) were the drugs of choice, with 30% of the sample reporting injecting
      drug use (58% of this subset reported injecting drug use within the past 30
      days). Substance-abusing youth were 3.6 times more likely to use drugs during
      sex, 2.2 times more likely to engage in survival sex, and 2.5 times more likely
      to have been diagnosed as having a sexually transmitted disease. CONCLUSIONS:
      High-risk sexual and drug use behaviors were prevalent and interrelated in this
      urban street youth sample. This suggests the need for new and innovative
      educational promotions and prevention interventions targeted to this population.

PMID- 7735404
TI  - Teenagers at risk of human immunodeficiency virus type 1 infection. Results from
      seroprevalence surveys in the United States.
AB  - OBJECTIVE: To describe the seroprevalence of human immunodeficiency virus type 1
      (HIV-1) and risk factors for HIV-1 infection among teenagers attending selected
      clinics. DESIGN: Anonymous, cross-sectional serosurveys conducted in 130 clinics
      in 24 cities. SETTINGS: Adolescent medicine clinics, sexually transmitted disease
      clinics, clinics in juvenile detention and correctional facilities, and homeless
      and runaway youth centers. PATIENTS: Teenagers in whom serum samples were drawn
      as part of routine medical services. MAIN OUTCOME MEASURES: Prevalence of HIV-1
      infection and reported HIV risk behaviors. RESULTS: From January 1, 1990 through
      December 31, 1992, serum specimens were collected from 79,802 teenagers; 591 of
      these specimens were positive for HIV-1 antibody. Seropositive test results were
      found in all 24 cities surveyed, and in 95 (73%) of the 130 clinics surveyed. The
      median clinic-specific prevalence was 0.2% (range, 0% to 1.4%) in 22 adolescent
      medicine clinics, 0.3% (range, 0% to 6.8%) in 33 correctional facilities, 0.5%
      (range, 0% to 3.5%) in 70 sexually transmitted disease clinics, and 1.1% (range,
      0% to 4.1%) in five homeless youth centers. Rates exceeded 1% in 37 sites (28%).
      Excluding sites with many men reporting sex with men, rates in women were similar
      or somewhat higher than rates in men. Rates were highest among young men
      reporting sex with men, with clinic rates ranging from 16% to 17% in two homeless
      youth sites and 13% to 17% in two sexually transmitted disease clinics. Most
      teenagers with risk information reported heterosexual activity as their only
      potential risk exposure to HIV-1. CONCLUSIONS: Seroprevalence of HIV was
      generally low but varied by type of clinic and geographic area. The highest rates
      were observed among young women and gay men in some settings, suggesting that
      targeted prevention messages are needed.

PMID- 7735405
TI  - Prevalence of corporal punishment among students in Washington State schools.
AB  - OBJECTIVES: To determine the prevalence of corporal punishment in Washington
      State and the factors associated with its use in Washington elementary and
      secondary schools. DESIGN: Cross-sectional mail survey performed during the
      summer of 1992. SETTING: All elementary and secondary schools in the state of
      Washington. RESULTS: One thousand eighteen schools (47%) responded to the survey,
      of which 80% were publicly funded and 63% were located in urban areas. The study
      sample closely resembled the profile of all schools in the state. Almost 11% of
      participating schools permitted corporal punishment at the time of the survey and
      3.2% reported its actual use during the 1991-1992 school year, resulting in an
      estimated prevalence of 7.2 incidents per 1000 students per year. Sixteen percent
      of corporal punishment actions occurred in schools not permitting its use. Ninety
      percent of public schools relied on district policy regarding corporal
      punishment. School characteristics associated with the use of corporal punishment
      included rural location (crude odds ratio, 2.2; 95% confidence interval, 1.5 to
      3.4), enrollment of less than 500 students (crude odds ratio, 1.7; 95% confidence
      interval, 1.1 to 2.7), and kindergarten to eighth-grade or kindergarten to 12th
      grade enrollment (crude odds ratio, 2.5; 95% confidence interval, 1.6 to 3.9).
      CONCLUSIONS: The lack of a statewide ban on school corporal punishment at the
      time of this survey was associated with the continued use of corporal punishment
      against children in districts that continued to permit it. School policies
      against corporal punishment were associated with much lower prevalence. Continued
      efforts are needed to enact and enforce laws in the remaining states that have
      not yet banned corporal punishment.

PMID- 7735406
TI  - Infantile colic. Seasonal incidence and crying profiles.
AB  - OBJECTIVES: To determine the occurrence of infantile colic and its seasonal
      variation in an unselected population and to evaluate the amounts of crying in
      colicky infants and noncolicky controls. DESIGN: Questionnaire survey and a
      prospective substudy of parental diaries of crying. SETTING: All families with a
      full-term, healthy-born infant in the Turku City (Finland) district during 1
      year. PARTICIPANTS: Colic was defined as paroxysms of crying for 3 or more hours
      per day for 3 days or more per week during a period of at least 3 weeks. The
      questionnaires containing this definition were distributed to 1221 families in
      postpartum wards, and an invitation to a prospective follow-up study was
      presented to the families if their infant showed colicky symptoms. The incidence
      questionnaire was to be returned after 3 months. Six hundred four (49%) of the
      questionnaires were returned, and an additional 355 (29%) families were reached
      by phone. A total of 59 families with a colicky infant enrolled in the
      prospective substudy when the infants were at a median age of 5 weeks; age
      matched controls were invited from the same population. RESULTS: The incidence of
      infantile colic was 13%; possible infantile colic was 8%. No seasonal variation
      was found. The mean amount of total crying was 241 min/d (95% confidence interval
      [CI], 216 to 266 minutes) in the colic group and 112 min/d (95% CI, 95 to 130
      minutes) in the control group during the first recording week. The mean amount of
      colicky crying was 122 min/d (95% CI, 102 to 142 minutes) in the colic group and
      19 min/d (95% CI, 12 to 26 minutes) in the control group. CONCLUSIONS: The
      incidence of colic was 13% with no seasonal variation. Parental perception of
      infantile colic correlated well with the amount of crying.

PMID- 7735407
TI  - Epidemiology, etiology, and clinical features of septic arthritis in children
      younger than 24 months.
AB  - OBJECTIVE: To examine the incidence, etiology, and clinical features of septic
      arthritis in patients younger than 24 months. DESIGN: Retrospective, 1988 through
      1993 period, chart review-based survey. PATIENTS: All children with
      bacteriologically proved septic arthritis that was diagnosed at a medical center
      serving southern Israel (population 320,000). Septic arthritis was defined by
      clinical evidence of joint inflammation and a positive synovial fluid or blood
      culture, antigen detection test, or a standard tube agglutination titer of 160 or
      greater for Brucella species. INTERVENTIONS: None. RESULTS: During the 6-year
      period, 40 children had septic arthritis diagnosed. Twenty-six (65%) were male.
      The annual incidence of septic arthritis was 37.1 per 100,000. The two most
      common organisms isolated were Kingella kingae in 19 (48%) and Haemophilus
      influenzae type b in eight (20%). The clinical presentation was frequently mild:
      a body temperature of less than 38.3 degrees C was recorded in 14 (35%) of 40
      children, leukocyte count of less than 15 x 10(9)/L in 13 (34%) of 38, and
      erythrocyte sedimentation rate of less than 30 mm per hour in four (11%) of 35.
      In eight (36%) of 22 patients, less than 50 x 10(9)/L leukocytes were counted in
      the synovial fluid. CONCLUSIONS: The diagnosis of septic arthritis in young
      children requires a high index of suspicion, and the disease cannot be excluded
      on the basis of lack of fever or normal results of laboratory tests. Kingella
      kingae appears to be the most common cause of septic arthritis in patients
      younger than 24 months, although confirmatory studies from other geographic areas
      are still needed.

PMID- 7735408
TI  - The rest of the access-to-care puzzle. Addressing structural and personal
      barriers to health care for socially disadvantaged children.
AB  - A mother brings her 2-year-old child to the office at 4:30 Friday afternoon. The
      child has been seen only once in the practice for an episode of otitis media. The
      child missed her follow-up appointment. When the receptionist asks why the child
      is here, the mother responds that she was able to get a ride today with a
      neighbor who has an appointment with another physician in the practice. The child
      is not covered by health insurance. The mother did not bring her immunization
      record and is not certain what preventive care the child has received in the
      past.

PMID- 7735409
TI  - Radiological case of the month. Arteriovenous malformation.

PMID- 7735410
TI  - Picture of the month. Monilethrix.

PMID- 7735411
TI  - Pathological case of the month. Pilomatrixoma.

PMID- 7735412
TI  - How well they remember. The accuracy of parent reports.
AB  - OBJECTIVES: To determine the range of accuracy of parent recall for many
      different events when compared with pediatrician's records and to establish
      whether good recall is associated with the nature of the event, period of recall,
      or demographic characteristics. RESEARCH DESIGN: A nonconcurrent, descriptive
      survey of previous events. SETTING: Two pediatric group practices in Montreal,
      Quebec. PARTICIPANTS: Two hundred eighty-eight parents of children aged 1 to 13
      years. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Parents' responses to a
      self-administered questionnaire were compared with information extracted from
      pediatricians' records. The health events studied included asthma, bronchitis,
      otitis media, accidents, hospitalizations, office visits, and birth weight. Most
      parents (73%) were able to recall birth weight within 50 g, and 85% reported a
      frequency of hospitalizations that agreed exactly with the record. For asthma,
      bronchitis, and otitis in the last year, the percentages with good agreement were
      91%, 85%, and 51%, respectively, while for the same disorders during the child's
      lifetime, the corresponding figures were 87%, 74%, and 53%, respectively. Each
      parent's responses were classified according to overall quality of agreement;
      associations between agreement and respondent characteristics were investigated.
      Mothers responded more accurately than fathers, and parents of younger children
      also showed better recall. Other factors, eg, education and occupation, were not
      significantly correlated with recall. CONCLUSIONS: When compared with
      pediatricians' records, parent reports are generally acceptable for most research
      purposes and may be a better source for some health events such as accidents.

PMID- 7735413
TI  - Immunization coverage among infants enrolled in the Tennessee Medicaid program.
AB  - OBJECTIVES: To determine immunization coverage of infants receiving Medicaid in
      Tennessee and to identify risk factors for failure to complete recommended
      vaccinations by 24 months of age. DESIGN: Retrospective cohort study. SUBJECTS: A
      total of 33,615 children born in one of three urban Tennessee counties from 1980
      through 1989 who were enrolled in Medicaid throughout their first 24 months of
      life. MAIN OUTCOME MEASURES: Receipt of four diphtheria-tetanus-pertussis, three
      oral polio, and one measles-mumps-rubella vaccines by 24 months of age (up-to
      date), as recorded in computerized county immunization records and Medicaid
      billing files. RESULTS: Overall, 45% of infants enrolled in Medicaid in the three
      urban counties completed the recommended vaccinations by 24 months. The
      proportion of infants up-to-date peaked at 50% for those born in 1982 and 1983,
      and decreased to 44% for those born in 1989. The only strong independent
      predictors of immunization completion were number of prior births for the mother,
      timing of the first immunization, and county of birth. The proportion up-to-date
      was 56% for first-born children compared with 27% for those whose mothers had at
      least three prior births; 55% for those whose first immunization was on time
      compared with 22% for those with a delay in the first immunization; and 63%, 52%,
      and 37% for infants born in the three respective counties. Maternal age,
      education, race, and marital status predicted immunization completeness only
      weakly or not at all. CONCLUSIONS: Of infants born in the three counties in the
      1980s who were enrolled in the Tennessee Medicaid program, fewer than half
      completed their recommended childhood vaccinations by 24 months of age. The large
      differences in immunization levels between infants enrolled in the Medicaid
      program in the three counties, not accounted for by differences in demographics,
      suggest that factors related to the health care and vaccine delivery system have
      important effects on achieving adequate immunization of these infants.

PMID- 7735414
TI  - Prevalence of behavior problems in US children with asthma.
AB  - OBJECTIVES: To present national population-based estimates of the prevalence of
      parent-reported emotional and/or behavioral problems in children with asthma and
      the relationship of medical comorbidity and asthma severity with behavior
      problems. DESIGN: Cross-sectional study of the 1988 National Health Interview on
      Child Health. MAIN OUTCOME MEASURES: Parent responses to a checklist of child
      health conditions were used to assign school-age children (5 to 17 years old)
      into one of four groups: children without reported chronic conditions; children
      with asthma alone; children with asthma and additional reported chronic
      conditions; and children with the same chronic conditions, but without asthma.
      Parental responses to the Behavior Problem Index (BPI) were used for construction
      of an overall BPI score, as well as subscale scores. Cross-tabulation and linear
      and logistic regression were used to determine the relation of the different
      condition categories to emotional and/or behavioral problems expressed by
      relative values of the BPI. RESULTS: Children with asthma and comorbid conditions
      had a mean BPI score of 7.3, compared with 5.4 for children without chronic
      conditions, and all subscale scores, except those for antisocial conduct and
      immature behavior, were significantly elevated. Using logistic regression to
      control for confounding variables, children with severe asthma alone had nearly
      three times the odds (odds ratio, 2.96; 95% confidence interval, 1.22 to 7.17)
      and children with asthma plus comorbid conditions nearly twice the odds (odds
      ratio, 1.86; 95% confidence interval, 1.20 to 2.90) of children without chronic
      conditions to have severe behavior problems. CONCLUSIONS: Severe asthma and
      asthma with medical comorbidity represent significant risk factors for emotional
      and/or behavioral problems. Clinicians caring for children with asthma and their
      families should be aware of the relationship between asthma and emotional and/or
      behavioral problems and anticipate that a substantial number of their patients
      may have mental health services needs.

PMID- 7735415
TI  - Intracranial assessment of incontinentia pigmenti using magnetic resonance
      imaging, angiography, and spectroscopic imaging.
AB  - OBJECTIVE: To evaluate patients with incontinentia pigmenti for evidence of
      cerebrovascular disease using magnetic resonance imaging techniques. DESIGN: A
      prospective case series of seven patients (four of whom were related) with
      incontinentia pigmenti using magnetic resonance imaging, magnetic resonance
      angiography, and multislice proton (1H) magnetic resonance spectroscopic imaging.
      SETTING: The Johns Hopkins Medical Institutions, Baltimore, Md, a tertiary,
      referred care center. PATIENTS: Seven patients with a diagnosis of incontinentia
      pigmenti. RESULTS: Five of the seven patients had abnormal magnetic resonance
      imaging consistent with small-vessel occlusions. Of these five patients, four had
      normal magnetic resonance angiography and spectroscopic imaging, and one patient
      had reduced middle cerebral artery flow on magnetic resonance angiography and
      increased lactate level in the cerebrospinal fluid on spectroscopic imaging. The
      remaining two patients had normal magnetic resonance imaging and spectroscopic
      imaging. Of these two patients, one had normal magnetic resonance angiography and
      the other had a right supraclinoid internal carotid aneurysm. There was
      substantial concordance between clinical (ophthalmic/neurologic) and imaging
      abnormalities. CONCLUSIONS: The central nervous system changes in patients with
      incontinentia pigmenti may represent the result of small-vessel occlusive
      phenomena in the brain. These central nervous system findings may share a common
      pathophysiologic state with the vascular occlusive disease seen in the retinas of
      these patients. The changes in the retinal vasculature may serve as a potential
      marker for central nervous system disease. Physicians should be aware of the
      systemic and debilitating nature of incontinentia pigmenti.

PMID- 7735416
TI  - Newborn human immunodeficiency virus testing in New York: a legislative quandary.

PMID- 7735417
TI  - Children and their diseases.

PMID- 7735418
TI  - [Comparative study of nebulized sambutol against placebo in the acute phase of
      bronchiolitis in 33 infants aged 1 to 6 months].
AB  - BACKGROUND: The therapeutic role of bronchodilators in bronchiolitis remains
      controversial. The aim of this study is to evaluate the safety and the clinical
      response to nebulized salbutamol in infants with mild acute bronchiolitis.
      PATIENTS AND METHODS: Thirty-three infants, aged 1 month to 5 months and 22 days
      (mean: 92.4 days) were included in the study. Patients received either nebulized
      salbutamol (0.15 mg/kg per dose: 16 infants) or a placebo (normal saline aerosol:
      17 infants), delivered by an oxygen propellent, three times at intervals of 1
      hour, as part of a double-blind randomized trial. Effect of treatment was
      evaluated by measuring respiratory and heart rate, clinical scores based on the
      degree of retraction and wheezing, and oxygen saturation. Clinical assessment was
      repeated 30 minutes after each nebulization. A nasopharyngeal swab was obtained
      for detection of respiratory syncytial virus (VRS) antigens by immunofluorescence
      assay in all patients. RESULTS: Patients in the salbutamol group exhibited
      significantly greater improvement in respiratory rate (P = 0.01), accessory
      muscle score (P < 0.001) and wheezing score (P < 0.001). There was no significant
      difference in oxygen saturation between both groups. Infants treated with
      salbutamol exhibited a non-significant increase in heart rate after the three
      sprays; no other adverse effects were noted. VRS was identified in 78% of the
      children tested. CONCLUSIONS: Salbutamol is safe and effective in relieving the
      respiratory distress of young infants with acute bronchiolitis. Our study
      confirms previous observations that infants younger than six months of age
      respond as well as older children when given three doses of nebulized salbutamol.
      Responders could not be differentiated from non responders by personal or family
      histories of atopy and VRS isolation. A longitudinal study could establish a
      correlation between response to bronchodilator therapy and later development of
      asthma.

PMID- 7735419
TI  - [Handicaps in the perinatal period. I. Perinatal pathology and difficulties in
      school].
AB  - BACKGROUND: Major handicaps are closely related to perinatal events. However,
      relationship of these events with other moderate disabilities such as school
      problems are still unclear. POPULATION AND METHODS: A representative sample of
      1,408 children at school age and born in Lorraine in 1984 was studied. Two
      hundred and fifty children with problems were compared with 602 controls without
      school problems, using a multivariate analysis. RESULTS: The incidence of school
      difficulties among 6-year old children (in the last year of nursery school) is
      17.8%. Children are at higher risk of school problems if their parents are not
      (odds ratio [OR] = 7.9) or are poor school graduate (OR = 2.7), if they are boys
      (OR = 2.0), if they are born at the end of the year (OR = 1.1) and also if they
      are preterm (OR = 2.7) or small for gestational age (OR = 2.5). Preterm delivery
      and intra-uterine growth retardation accounted for 9.6% of school difficulties.
      CONCLUSION: The relationship between perinatal events and school difficulties
      warrants to continue with prevention during pregnancy, especially among groups
      with multiple risk factors.

PMID- 7735420
TI  - [Peanut sensitization and oily solution vitamin preparations].
AB  - BACKGROUND AND METHODS: Early sensitization to peanut can occur through milk
      formulas which contain peanut oil. Thus, the groundnut allergens in relation to
      the early feeding have been systematically tested in all children referred to the
      paediatric allergy unit for symptoms not related to peanut allergy. RESULTS: Out
      of 102 children, 4 to 35 months old, 19 had a positive test (weal > 3 mm).
      Neither breast feeding nor milk formulas changed the frequency of sensitization.
      On the contrary, vitamin D preparations in groundnut oil significantly increased
      the risk (p < 0.008). Odds ratios were 5.47 in the case of neonatal prescription,
      4.82 in case of delayed prescription. Odds ratio increased to 8.25 (p < 0.04) in
      allergic children under two years who had received oily vitamin D preparation
      during their neonatal period. CONCLUSIONS: The result suggest to leave groundnut
      oil out of all foods and drugs given to infants and young children, as required
      for infantile milk formulas.

PMID- 7735421
TI  - [Bacteriological study of purulent otitis media in children in CHU in the
      tropical zone].
AB  - BACKGROUND: Haemophilus influenzae and S pneumoniae are the most common causative
      agents of acute otitis media in Europe and the USA. This work aimed to identify
      the agents in Senegal and to study their sensitivity to antibiotics. POPULATION
      AND METHODS: Two hundred and one patients, aged 0 to 15 years, with persistent
      middle-ear effusion, were included in this study from 1983 to 1993. Purulent
      samples aspirated from the external canal were analysed for bacteriology and
      sensitivity testing. RESULTS: Eighty two percent of cultures were positive for
      Staphylococcus aureus (37%), Pseudomonas aeruginosa (25%), Proteus (18%) and
      Klebsiella (8%). Positive cultures were found mainly in children aged between 1
      and 5 years. Amikacin and cefotaxim were the most active antibiotics against the
      majority of strains. Staphylococcus aureus was always resistant to penicillin.
      CONCLUSIONS: Prevalence of Staphylococcus aureus as the causative agent of
      persistent middle-ear effusion may be explained by late examination. Its
      resistance to penicillin favors early administration of third generation
      cephalosporins or pristanimycin.

PMID- 7735422
TI  - [Blood sampling on paper for neonatal screening. Guidelines for sampling,
      treatment and preservation of samples. Association francaise pour le depistage et
      la prevention des handicaps de l'enfant (AFDPHE)--Comite d'ethique].

PMID- 7735423
TI  - [Myositis ossificans progressiva].
AB  - BACKGROUND: Myositis ossificans progressiva is a rare progressive disease of
      connective tissue with a poor prognosis. CASE REPORT: A 16 year-old girl suffered
      from lameness of her right leg associated with inguinal swelling. Progressive
      aggravation of pain with extension of swelling to the posterior part of her thigh
      required an X-ray examination which showed hip dysplasia and calcifications
      around the hip. Angiography was normal; a diagnosis of hematoma was suggested by
      scannography and bone scintigraphy, but biopsy showed features of nodular
      fasciitis. The association of progressive ectopic ossification to malformation of
      the big toe led to diagnosis of myositis ossificans progressiva. CONCLUSIONS:
      Congenital malformations, most commonly of big toes and thumbs, are important for
      distinguishing myositis ossificans progressiva from other diseases of muscle.

PMID- 7735424
TI  - [Acute lipid pneumopathy].
AB  - BACKGROUND: Lipid pneumonia in children has rarely been described in Europe. In
      some countries, due to local customs, the course is chronic. This study describes
      an acute lipid pneumonia in a young boy. CASE REPORT: A 12 year-old boy,
      previously treated for a rhabdomyosarcoma, developed acute fever with thoracic
      pain. A chest radiograph revealed heterogenous consolidation. The patient was
      given oral antibiotics, although no improvement was observed. The diagnosis of
      lipid pneumonia was made by a bronchoscopy with bronchoalveolar lavage. Treatment
      with corticosteroids was started. Clinical manifestations improved rapidly. One
      month later, chest radiograph and biological findings were normal. CONCLUSION:
      Diagnosis of lipid pneumonia should be considered in children with an acute
      febrile pneumonitis non resolving with antibiotic treatment. Examination of the
      fluid obtained by bronchoalveolar lavage confirms the diagnosis.

PMID- 7735425
TI  - [Arterial hypertension due to mercury poisoning: diagnostic value of captopril].
AB  - BACKGROUND: Mercury poisoning is a rare cause of hypertension in children.
      Urinary excretion sometimes remains low despite severe clinical intoxication.
      CASE REPORT: A 32 month-old girl was admitted with hypertension, tachycardia,
      apathy, irritability and excessive sweating. Erythromelalgia and neurologic
      symptoms permitted the diagnosis of acrodynia. Urine mercury remained normal
      until chelation. Captopril significantly increased urine mercury concentration
      but failed to improve clinical manifestations. Clinical improvement required
      infusions of BAL for 5 days then oral dimercaptosuccinic acid for 3 months. Metal
      vapors originated from the mercury which spilled from a broken thermometer onto
      the carpet. COMMENTS: Low basal urine mercury could be associated with real
      mercury poisoning. Small amounts of metal mercury held in a thermometer could
      produce a high level of mercury vapor leading to intoxication in young children.
      The binding capacity of metal ions by captopril could be used to increase urine
      mercury output. Nevertheless, captopril therapy fails to improve acrodynia. Total
      elimination of mercury requires long-term therapy with BAL or dimercaptosuccinic
      acid. CONCLUSIONS: An unexpected mode of intoxication and low basal urine mercury
      are not decisive arguments against mercury poisoning, which is the only cause of
      acrodynia.

PMID- 7735426
TI  - [Favorable outcome of orbital nasal sinus mucormycosis complicating the induction
      treatment of acute lymphoblastic leukemia].
AB  - BACKGROUND: Most cases of mucormycosis occur in immunosuppressed children.
      Intracranial extension is lethal and must be prevented with early specific
      treatment. CASE REPORT: A 42 month-old boy was admitted suffering from acute
      lymphoblastic leukemia. Edema of the left eyelid developed on the sixth day of
      induction chemotherapy. Mucormycosis was suspected because of gradual extension
      of infection to nasal ala and periorbital area with fever, edema of nasal
      turbinates and nasal black secretions. Chemotherapy was discontinued and the
      patient was given intravenous amphotericin B (1.0 mg/kg/day) and heparin
      associated with G.CSF. Improvement was only temporary and scan examination
      performed on day 17 showed involvement of the orbit, eye and wall of the
      maxillary sinus; cultures of secretions were positive for staphylococcus and
      Absidia corymbifera. Remission of leukemia was obtained a few days later
      permitting surgical resection of involved tissues on day 30. A relapse of
      mucormycosis was observed six weeks later despite prolonged administration of
      amphotericin B requiring extended resection of necrotic areas and replacement of
      amphotericin B by its liposomal form (Ambisome). Bone marrow relapse of leukemia
      required further chemotherapy. The patient is in good condition 30 months after
      the initial symptoms. CONCLUSION: Our patient seems to be the first with
      prolonged remission of facial mucormycosis and acute leukemia despite relapse of
      both diseases. This favorable outcome could be due to the use of Ambisome.

PMID- 7735427
TI  - [Hamartomatous dysplasias with hemihypertrophy. 2 cases including one with
      Proteus syndrome].
AB  - BACKGROUND: Hamartomatous dysplasias with hemihypertrophy are a part of several
      congenital diseases, sometimes difficult to classify when their symptomatology is
      relatively poor. CASE REPORTS: Case 1. A girl, 11 year-old, suffered from
      gigantism of the feet, left hemihypertrophy of the limbs, scoliosis and kyphosis.
      X-rays showed frontal hyperostose, bony and soft tissues overgrowth involving the
      left limbs and pelvis with hip dislocation and coxa valga. The vertebrae were
      hypertrophic and dysplastic. No tumor could be found. Case 2. A girl, 18 year
      old, suffered from left hemihypertrophy of limbs and face associated with
      homolateral cutaneous hemangioma. X-rays showed enlargement of bone and soft
      tissue. No tumor or venous abnormalities were observed. CONCLUSION: A diagnosis
      of Proteus syndrome was made in the first patient while the second patient was
      considered to have Klippel-Trenaunay syndrome even though hemangiomatous
      involvement has been seen in Proteus syndrome.

PMID- 7735428
TI  - [Enuresis and benign micturition disorders in childhood. I. Diagnosis and
      management].
AB  - Bedwetting is present in 5 to 7% of children aged 7 to 8 years. The history of
      the disorder and the examination of the child are of main importance. This is
      usually the first step to identify nocturnal enuresis, bladder or urethral
      instability and other voiding dysfunctions. Therapeutic failure is often related
      to an inadequate analysis of the disorder. For nocturnal enuresis, the best
      results are obtained with alarms and/or desmopressine; bladder instability
      usually requires oxybutinine chlorydrate and urethral instability can be treated
      with biofeedback therapy. The management of other voiding dysfunctions depends on
      urodynamic assessment.

PMID- 7735429
TI  - [Enuresis and benign micturition disorders in childhood. II. Cost of the
      management].
AB  - The financial cost of bedwetting management is often underestimated. A study
      including 48 children aged 6 to 16 years was carried out in the outpatient clinic
      in order to evaluate the cost of these disorders during a 4 month-period. The
      diagnosis was the following: nocturnal enuresis (n = 15), bladder instability (n
      = 22) and other voiding dysfunction (n = 11). Our results showed that these
      expenses were quite important. A relationship between the kind of voiding
      dysfunction and the subsequent expenses was observed: the more complex was the
      disorder, the more expensive it was (average expenses = 1317 FF/year for
      nocturnal enuresis, 2506 FF/year for bladder instability and 3174 FF/year for
      other dysfunctions). Subsidiary expenses (transport, diapers and extrawashing)
      constituted an important part of the whole expenses: 46% in nocturnal enuresis,
      42% in bladder instability and 38% in other dysfunctions.

PMID- 7735430
TI  - [Hereditary motor and sensory neuropathy of Charcot-Marie-Tooth disease].
AB  - Charcot-Marie-Tooth disease (Hereditary Motor and Sensory Neuropathy) sometimes
      begins during childhood and can lead to learning and/or orthopedic disabilities.
      Due to the genetic and clinical heterogeneity of the disease, the diagnosis is
      based on a familial study of clinical, electromyographic and pathological
      abnormalities. Two major types of Charcot-Marie-Tooth disease have been
      described. Type 1 is characterized by a decrease in nerve conduction velocities
      and by a peripheral nerve hypertrophy due to myelinic alterations, while type 2
      is the consequence of axonal alterations. Although type 1 and type 2 patients
      share similar clinical symptoms, type 2 patients have normal nerve conduction
      velocities and histological signs of axonal damage. Several genes involved in
      this disease have been recently located, and, in certain cases, an individual and
      direct diagnosis is available if the familial abnormality is related to
      chromosome 17.

PMID- 7735431
TI  - [Surfactants in the digestive tube].
AB  - Epithelia of the gastrointestinal tract both synthesize and secrete surfactant
      like materials. Like the pulmonary surfactant, these materials contain not only
      phospholipids, but also surfactant apoproteins, regarded until recently as
      specific products of the bronchoalveolar epithelium. Presented here are the
      various roles, most of them still speculative, of these phospholipids-containing
      products in the gastro-intestinal tract.

PMID- 7735432
TI  - [Must the perspective of the gene therapy modify the screening strategy of cystic
      fibrosis?].

PMID- 7735433
TI  - [Treatment of acute otitis media].
AB  - The treatment of acute otitis media (AOM) has three main aims: to relieve pain,
      to control fever and in case of suppurative AOM, to overcome the bacterial
      infection. The two former aims are best managed with salicylates or paracetamol.
      The local instillation of drops of an anaesthetic-antiseptic solution in the
      external canal is a useful adjuvant in painful congestive viral otitis.
      Antibiotherapy is only indicated in suppurative AOM. The most common organisms
      being Haemophilus influenzae and Streptococcus pneumoniae, amoxicillin is the
      first line treatment. However, in children who were treated for suppurative AOM
      in the previous months, amoxicillin/clavulanic acid or a second generation
      cephalosporin is preferable. Erythromycin-sulfonamide may also be used,
      particularly in children who are allergic to beta-lactamines. In case of failure
      of the first choice antibiotic treatment, it is necessary to perform a
      bacteriological study of the effusion which will determine the appropriate
      antibiotic to be used in second hand. The duration of the antibiotic treatment
      must be of 8 days in the absence of spontaneous perforation, and of 10 days in
      case of perforation. An examination of the tympanum at 10 days is recommended in
      infants under 6 months of age and in children with repeated AOM. A myringostomy
      is only indicated when a bacteriological evaluation is needed, mainly in infants
      under 6 months of age, in immuno-compromised children, and in case of failure of
      a first line antibiotic treatment.

PMID- 7735434
TI  - [Bone pain revealing parathyroid adenoma].

PMID- 7735435
TI  - [Intestinal amebiasis revealing hemorrhagic rectocolitis in children].

PMID- 7735436
TI  - [Demographic decline in Russia and the health status of children].

PMID- 7735437
TI  - [Hepatitis A and acute glomerulonephritis].

PMID- 7735438
TI  - [Retrovirus, hepatitis B and C virus markers in milk and blood donors].

PMID- 7735439
TI  - [Perinatology in France in 1994].

PMID- 7735440
TI  - [Evolution of blood transfusion economy techniques in pediatric orthopedic
      surgery].

PMID- 7735441
TI  - [Brain functional imaging in children. Progresses and perspectives].

PMID- 7735442
TI  - [Handicaps and the perinatal period. II. Perinatal pathology and severe
      deficiencies].
AB  - BACKGROUND: In the last two decades, the infant mortality rate has dramatically
      declined. But improved management of newborns may induce an increased prevalence
      of neurodevelopmental handicaps. The aim of this paper is to estimate the rate of
      major disabilities and their relationships to perinatal events. POPULATION AND
      METHODS: Three hundred and sixteen children born in 1984 and registered by the
      "Commission Departementale de l'Education Speciale" (CDES) were included in the
      study. Among these, 97 had either cerebral palsy, blindness, deafness, or mental
      retardation. These 97 children were compared to 602 school age controls using a
      multivariate analysis (logistic regression). RESULTS: The rate of major
      disabilities among the 6-year old children is 3.4/1000. It was 5/1000 in 1972 and
      4.3/1000 in 1976. This frequency is higher in the children who were preterm (odds
      ratio--OR = 4.8), small for gestational age (OR = 3.3) or suffered from perinatal
      asphyxia (OR = 32.8). These three factors accounted for 37.4% of major
      disabilities. CONCLUSION: This study emphasizes the relationships between
      perinatal events and some major handicaps but also shows that antenatal factors
      may be involved in neurodevelopmental problems.

PMID- 7735443
TI  - [Transient erythroblastopenia in early childhood].
AB  - BACKGROUND: Transient erythroblastopenia is rare in young children although its
      frequency is increasing. POPULATION AND RESULTS: Six infants (four boys, two
      girls), aged 29-41 months (mean: 33) were admitted for polar and asthenia. Only
      one displayed infectious episode two months earlier. Hemoglobin ranged from 40 to
      67 g/l and reticulocyte number from 1 to 10 G/l. Mean corpuscular volume was
      normal as was Coombs' test. There was a profound erythroblastopenia in the bone
      marrow in five of the six patients. Parvovirus B19 infection was excluded in all.
      The white cell and platelet counts were normal. All patients were given an unique
      blood transfusion. Reticulocytosis spontaneously appeared within a few weeks in
      three patients. Another patient had normal number of erythroid precursors in the
      bone marrow 1 month after admission. CONCLUSION: Diagnosis of transient
      erythroblastopenia can only be made after exclusion of known causes such as
      drugs, virus, immune deficiency, leukemia and of Blackfan-Diamond disease. Its
      persistence must lead to search for another cause.

PMID- 7735444
TI  - [Suicidal children and adolescents].
AB  - BACKGROUND: Psychiatric evaluation of suicide attempters is necessary in order to
      define aspects of primary and secondary prevention of suicidal behavior.
      POPULATION AND METHODS: All the 80 children and adolescents (66 girls and 14
      boys) admitted from September 1989 to September 1992 in a pediatric hospital for
      suicide attempt have been included in this study. Their mean age was 13 yr 10 mo
      +/- 1.4 and 81% of them were more than 13 years of age. Evaluation included a
      structured interview and a scale assessing general psychopathology. RESULTS: Risk
      factors included previous psychiatric history in the patient (47%), family
      history of psychiatric disturbances in 33% of the mothers, 15% of the fathers and
      13% in both. Recent modification in familial composition was seen in one third of
      cases and chronic difficulties in parent/child interaction in 92%. A relationship
      between the non impulsivity of the suicidal gesture, psychiatric history and
      depression diagnosed at the time of evaluation was also recognized. CONCLUSIONS:
      Knowledge of these risk factors should help to prevent and treat some aspects of
      suicidal behavior.

PMID- 7735445
TI  - [Comparative study of cefixime versus amoxicillin-clavulanic acid combination in
      the oral treatment of urinary tract infections in children].
AB  - BACKGROUND: Acute febrile infections suggestive of pyelonephritis require
      treatment by broad-spectrum antibiotics capable of reaching significant tissue
      levels. This study compares efficacy and safety of cefixime with amoxycillin +
      clavulanic acid in urinary tract infections. POPULATION AND METHODS: Fifty seven
      children aged 5 months to 14 years treated for urinary tract infection in ten
      pediatric centres for a period of 10 months had been randomly included in the
      study. Thirty (22 girls and eight boys) were given cefixime and 27 (24 girls and
      three boys) amoxycillin-clavulanate. Efficacy was evaluated in only 36 patients
      whose bacteria were susceptible to both antibiotics (26 pyelonephritis and ten
      cystitis). RESULTS: Sixteen patients out of the 19 given cefixime recovered vs.
      14 out of the 17 given amoxycillin-clavulanate with no significant difference
      between both groups. Bacteria were more often susceptible to cefixime (100% of
      cases) than to amoxycillin-clavulanate (69%) (p < or = 0.0001). Safety was good
      and comparable in both groups. CONCLUSION: Cefixime given per os seems effective
      and safe in treating urinary tract infections. These results have to be confirmed
      by further studies.

PMID- 7735446
TI  - [Primary psoas abscess in children: 6 cases].
AB  - BACKGROUND: Primary psoas abscess is very rare in childhood; its diagnosis and
      treatment can be improved by the use of recent imaging techniques. PATIENTS: Six
      children, aged 11 months to 10 years (mean: 51 months) were admitted from January
      1987 to 15 December 1993 because they suffered mainly from fever, lumbar pain
      and/or homolateral flexed hip. Examination showed a painful inguinal mass in five
      patients and hyperleucocytosis in all. X-rays showed disappearance of the
      external limit of psoas in two patients; ultrasonography showed enlarged psoas in
      all, associated with hypoechogenic mass in two and without echo in four patients.
      CT scan showed the abscess in all cases, permitting a needle aspiration for
      bacteriological studies: Staphycococcus aureus was present in five cases.
      Drainage of the abscess by CT-guided percutaneous catheter was performed in two
      patients. Surgical drainage was performed in three including one for whom
      percutaneous catheter drainage did not succeed. The two other patients were only
      given antibiotics. CONCLUSION: CT-guided needle aspiration to establish presence
      and nature of fluid collection is a well established technique that may be
      extended to treatment of psoas abscesses.

PMID- 7735447
TI  - [Tuberculous dacryocystitis].
AB  - BACKGROUND: Acute infection and inflammation of the nasolacrimal sac may
      complicate congenital obstruction of the nasolacrimal duct. Acute dacryocystitis
      is uncommon later and tuberculosis is exceptionally responsible for it. CASE
      REPORT: A 4 1/2 year-old boy was admitted because he suffered from acute left
      dacryocystitis with fever and cervical adenitis. Involvement of both lacrymal
      gland and lymph node persisted despite antibiotic and corticosteroid therapy.
      Needle biopsy of the lymph node showed presence of Mycobacterium tuberculosis and
      excision revealed caseating granulomas. The tuberculin skin test was positive
      while pulmonary tuberculosis was discovered in the patient's father. The patient
      was successfully given izoniazid, rifampin for 9 months and pyrazinamide for 2.
      Drainage of the sac area was necessary after 1 month of treatment followed by
      dacryocystorhinostomy. CONCLUSION: This rare case of tuberculous dacryocystitis
      permits to delineate the difficulties of ophthalmologic therapy.

PMID- 7735448
TI  - [Non-traumatic myositis ossificans circumscripta].
AB  - BACKGROUND: Myositis ossificans circumscripta is a benign lesion with an acute
      course and may simulate a malignant tumor. It usually follows trauma to soft
      tissue. CASE REPORTS: Case n. 1. A 13 year-old girl was admitted because of a
      painful inflammatory tumour in the left thigh. Initial X-rays were normal.
      Ultrasound imaging showed a heterogeneous echogenic mass with several extending
      shadow cones in the distal part of the vastus medialis muscle resembling a
      calcifying hematoma. Twenty days later, X-rays showed a vague calcified
      peripheral rim in the medial distal part of the thigh. White blood count was
      normal, and blood sedimentation rate was 46 millimeters in the first hour. CT
      scan showed a transparent zone between the lesion and the adjacent bone and a
      lucent central area, surrounded by a dense outer area consistent with myositis
      ossificans. Histological examination of the excised mass confirmed myositis
      ossificans. Two years later, the patient was asymptomatic and X-rays showed no
      ossification. Case n. 2. A 14 year-old girl suffered from pain in the right
      anterior hip area since 10 days. She denied any trauma. A firm mass was palpable
      in the anterior superior iliac spine area and X-rays revealed a calcific density.
      CT scan showed a dense bony mass in the right gluteus medius muscle clearly
      separated from the adjacent bony pelvis by a soft tissue plane. Histological
      examination of the excised mass confirmed myositis ossificans. One year later,
      the patient was asymptomatic and X-rays of the pelvis showed no ossification.
      CONCLUSION: Myositis ossificans circumscripta is rare in children. CT scan
      suggests the benign nature of the lesion by demonstrating integrity of bony
      cortex and characteristic disposition of calcifications. The biopsy is not
      necessary if the diagnosis is certain. Surgery permits to reduce the evolution.

PMID- 7735449
TI  - [Transient correction of partial congenital factor V deficiency in nephrotic
      syndrome].
AB  - Plasma concentration of several hemostatic proteins may be modified during the
      acute phase of nephrotic syndrome. The case of such a syndrome in a patient with
      congenital factor V deficiency is presented. CASE REPORT--A 5 year-old girl with
      partial congenital factor V deficiency (level: 30%), was admitted for nephrotic
      syndrome complicating Henoch-Schonlein purpura. Urine protein excretion was 4
      g/24 h. Initial plasma concentrations were: protein: 5.5 g/dl; albumin: 3.3 g/dl;
      factor II: 85%; factor V: 56%; factors VII + X: 80%. The patient was given
      methylprednisolone (1 g/1.73 m2) followed by prednisone (2 mg/kg/day). Under this
      treatment, the plasma concentrations were: protein: 4.5 g/dl; albumin: 2.0 g/dl;
      factor II: 180%; factor V: 84%; factors VII + X: 120%. Values at the onset of
      remission were: albumin: 3.4 g/dl; factor V: 49%. CONCLUSION--This observation
      suggests that hypoalbuminemia may enhance liver synthesis of factor V as known
      for some other coagulation factors, and transiently correct the hereditary
      deficiency.

PMID- 7735450
TI  - [Treatment of asthma crisis in children].
AB  - The occurrence of an acute exacerbation of asthma frequently reflects failure of
      a first line treatment that has to be reconsidered. Severe episodes of acute
      asthma are often related to non-recognition of signs of gravity, inadequate
      treatment and/or delayed access to an emergency department. Several consensus
      conferences have established guidelines for management of asthma attacks in the
      patient's home, and have defined the symptoms which should lead the physician to
      refer the patient to an emergency department and the criteria of hospitalization
      when the patient does not respond properly to the treatment. Guidelines for
      management of acute asthma based on the currently recommended therapeutic
      schedules are presented.

PMID- 7735451
TI  - [Maternal-fetal transmission of HIV].
AB  - HIV infection in children is mainly the result of a mother-to-child transmission.
      The contamination during pregnancy is well known but intrapartum vertical
      transmission may also occur through ascending infection, blood exchange between
      mother and child, or direct contact with vaginal or cervical secretions. In
      addition HIV can be transmitted via breast milk. The reported rates of vertical
      transmission are highly variable: 14.4% in a European study, 18.3% in a French
      survey, 20 to 25% in the USA, 35 to 50% in Africa. It is unclear whether such a
      large variation of the rate of transmission is due to methodological differences
      or to different distributions of risk factors in the populations. There are some
      known predictive factors of HIV transmission such as low CD4 cells count,
      positive p24 antigenaemia and elevated concentrations of virus. The role of other
      factors is still debated: prematurity, virus (CMV, HTLV-1, HVB, HVC), C section
      prior labour, rupture of membranes. The prevention of HIV infection in infants is
      mainly based on contra-indication of pregnancy in infected women, desinfection of
      the vagina at the beginning of labour, early protection of the newborn by
      avoiding skin lesions and immediate washing, preventive treatment by zidovudin
      during pregnancy.

PMID- 7735452
TI  - [Folic acid and pregnancy. Societe francaise de pdiatrie--Comite de nutrition].
AB  - Epidemiological studies have shown a relationship between maternal folic acid
      status and the incidence of neural tube defects, prematurity, abortions. Based on
      the actual data, the Committee of Nutrition recommends that all women at age of
      procreation should be encouraged to regularly eat fresh fruits and vegetables in
      order to increase their reserve of folic acid, and that pregnant and lactating
      women should be supplemented with a daily dose of 200 micrograms of folic acid.
      In addition, the Committee is in favour of a folacin enrichment of some food
      which would allow to cover the needs of pregnant and lactating women. Those women
      who gave birth to a child with neural tube defects must be informed of the high
      risk of recurrence and be encouraged to take a treatment of 4 mg/day of folic
      acid, ideally starting one month before the beginning of pregnancy and to be
      maintained during the first 3 months.

PMID- 7735453
TI  - [Radiological case of the month. Cystic meningioma of the posterior fossa].

PMID- 7735454
TI  - [External emergency care service for pediatric respiratory kinesitherapy in
      hospitals].

PMID- 7735455
TI  - [Head injuries after falling from bunk beds].

PMID- 7735456
TI  - [Pediatric neurologic emergencies in Brazzaville].

PMID- 7735457
TI  - [Neonatal diabetes mellitus caused by congenital absence of beta cells associated
      with methylmalonic acidemia due to uniparental disomy of chromosome 6].

PMID- 7735458
TI  - [Hypersensitivity to cow's milk protein hydrolysate (HCMPH) in infants. Value of
      prick tests].

PMID- 7735459
TI  - Multi-residue matrix solid-phase dispersion method for the determination of six
      synthetic pyrethroids in vegetables followed by gas chromatography with electron
      capture detection.
AB  - An effective multi-residue matrix solid-phase dispersion (MSPD) extraction and
      gas chromatographic-electron-capture detection method for the determination of
      six synthetic pyrethroids (fenpropathrin, cyhalothrin, permethrin, cypermethrin,
      fenvalerate and deltamethrin) in 5 g of vegetables (West Indian gherkin,
      eggplant, pak-choi, cabbage and garden peas) is described. The method uses a
      Florisil-based MSPD column for direct in-line clean-up with n-hexane-acetone
      (9:1). Recoveries calculated at 0.1 and 0.5 micrograms/g fortification levels
      were between 92 and 113%. The method detection limits were between 5.1 and 91.5
      ng/g. The method compared favourably with the traditional method in terms of the
      sample size, analysis time and overall cost. The method may serve as a screening
      protocol for the determination of pyrethroids in vegetables.

PMID- 7735460
TI  - Capillary electrophoresis of carboxylated carbohydrates. I. Selective precolumn
      derivatization of gangliosides with UV absorbing and fluorescent tags.
AB  - We demonstrate that the precolumn derivatization reaction, recently introduced by
      our laboratory for the selective labeling of carboxylated monosaccharides, can be
      readily transposed to other glycoconjugates containing carboxylated sugar
      residues, namely sialogangliosides. The selective derivatization reaction
      described here involved the attachment of sulfanilic acid (a UV-absorbing tag) or
      7-aminonaphthalene-1,3-disulfonic acid (a UV-absorbing and also fluorescing tag)
      to the sialic acid moiety of the gangliosides via the carboxylic group in the
      presence of water-soluble carbodiimide. This labeling of the sialic acid moiety
      of the gangliosides with a chromophore and/or fluorophore leads to the formation
      of an amide bond between the carboxylic group of the sugar residue and the amino
      group of the derivatizing agent, thus replacing the weak carboxylic acid group of
      the carbohydrate species by the stronger sulfonic acid group which is ionized
      over the entire pH range. Furthermore, novel electrolyte systems were introduced
      and evaluated for the separation of the derivatized and underivatized
      gangliosides. The addition of acetonitrile or alpha-cyclodextrin (alpha-CD) to
      the running electrolyte was necessary to break-up the aggregation of amphiphilic
      gangliosides and allowed for their efficient separation as monomers in aqueous
      media using capillary electrophoresis. Several operating parameters were
      investigated with these electrolyte systems including the additive concentration
      as well as the ionic strength, pH and nature of the running electrolyte.
      Acetonitrile at 50% (v/v) in 5 mM sodium phosphate at high and low pH or 15 mM
      alpha-CD in 100 mM sodium borate, pH 10.0, proved ideal, in terms of resolution
      and separation efficiency, for the group separation of mono-, di- and
      trisialogangliosides. On the other hand, the complete resolution of
      disialoganglioside isomers (e.g., GD1a and GD1b) necessitated the superimposition
      of a chromatographic component on the electrophoretic process. This was achieved
      by adding either a hydrophobic (e.g., decanoyl-N-methylglucamide-borate
      surfactant complex) or hydrophilic [e.g., poly(vinyl alcohol) or hydroxypropyl
      cellulose] selectors to the running electrolyte.

PMID- 7735461
TI  - Determination of the relative amounts of the B and C components of neomycin by
      thin-layer chromatography using fluorescence detection.
AB  - The determination of the relative amounts of the B and C components of neomycin
      sulphate by thin-layer chromatography using silica gel plates from Whatman as the
      stationary phase is described. The mobile phase consisted of methanol-20% (m/v)
      sodium chloride solution (15:85). Fluorescence detection was performed after
      derivatization with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole. The influence of
      different parameters on the separation was investigated. A number of commercial
      samples was analysed using this method and the results were compared with results
      obtained with ion-exchange chromatography and ninhydrin colorimetric detection,
      which is the official method prescribed by the European Pharmacopoeia. The
      described method is much easier to perform than the official method.

PMID- 7735462
TI  - Fluorescence, photodestruction, photoionization and thermal degradation of o
      phthalaldehyde/beta-mercaptoethanol-labelled aliphatic alpha-oligopeptides.
AB  - Photophysical and photochemical properties of o-phthalaldehyde/beta
      mercaptoethanol-labelled aliphatic alpha-peptides were investigated. It is found
      that alpha-peptide derivatives have lower fluorescence quantum yields, higher
      photodestruction quantum yields and lower yields for formation of solvated
      electrons as compared to amino acid and simple alkylamine derivatives in aqueous
      alkaline solution. These properties of the alpha-peptide derivatives sets narrow
      limits for their utilization in laser-based (high light intensity) detector
      systems. In contrast, the thermal stability of the peptide derivatives was found
      to be severalfold higher than for the parent amino acid derivatives. The
      differential rates of thermal derivative degradation could be utilized in a new
      approach towards selective determination of peptides. determination of peptides.
      determination of peptides.

PMID- 7735463
TI  - Rapid purification of cotton seed membrane-bound N-acylphosphatidylethanolamine
      synthase by immobilized artificial membrane chromatography.
AB  - N-Acylphosphatidylethanolamine synthase (NAPES) is a membrane-bound enzyme
      present in cotton seedlings at a concentration of < or = 0.02% of the total
      protein. NAPES was purified to electrophoretic homogeneity in a single
      chromatographic step using immobilized artificial membrane (IAM) chromatography.
      The IAM column used for NAPES purification was etherIAM.PEC10/C3 and this surface
      contains a monolayer of immobilized phosphatidyl-ethanolamine (PE). Since PE is
      an analogue of the natural substrate for NAPES, etherIAM.PEC10/C3 columns
      function as an affinity column for this enzyme. Detergent-solubilized microsomal
      proteins from cotton were loaded on to the etherIAM.PEC10/C3 column and eluted
      with buffered mobile phases containing 0.2 mM dimyristoylphosphatidylethanolamine
      (DMPE) and 2 mM dodecylmaltoside. Little NAPES functional activity eluted if DMPE
      was removed from the mobile phase. Mobile phase DMPE is also a substrate for
      NAPES, both the mobile phase and IAM surface contains NAPES substrates. Mobile
      phase DMPE may function as both a surfactant-type affinity displacing ligand
      effecting protein elution and also a stabilizing factor of NAPES functional
      activity. The loading capacity on semi-preparative etherIAM.PEC10/C3 (6.5 x 1.0
      cm) columns was ca. 5 mg of total detergent solubilized microsomal proteins, and
      protein recovery was quantitative. This one-step IAM purification of NAPES
      resulted in a single band on silver-stained polyacrylamide gels, and 3940 fold
      increase in NAPES specific activity. The molecular mass of the purified NAPES
      protein is 64,000. 125I labeled [12-(4-azidosalicyl)amino]dodecanoic acid is a
      photoreactive fatty acid substrate of NAPES that was used to confirm protein
      purity.

PMID- 7735464
TI  - Determination of codeine in human plasma by high-performance liquid
      chromatography with fluorescence detection.
AB  - A rapid, reliable and rugged assay for determining codeine in human plasma using
      reversed-phase high-performance liquid chromatography with fluorescence detection
      was developed. This analytical method utilized an ion-exchange/mixed-mode solid
      phase extraction procedure. The chromatographic separation was achieved using a
      150 x 4.6 mm I.D., 3-microns reversed-phase C8 (deactivated for basic analytes)
      column at ambient temperature. Fluorescence detection (excitation at 214 nm and
      emission above 345 nm) for codeine and nalorphine allowed for a detectable limit
      of 5 ng/ml. The results showed that the method was linear from 10 to 300 ng/ml.
      The method had good reproducibility, precision, accuracy and recoveries of 91 and
      90% for codeine and nalorphine, respectively. This method has been applied to
      study the pharmacokinetics of codeine in normal human subjects.

PMID- 7735465
TI  - Measurement of plasma testosterone by gas chromatography-negative-ion mass
      spectrometry using pentafluoropropionic derivatives.
AB  - Plasma testosterone was measured by gas chromatography-negative-ion chemical
      ionisation mass spectrometry (GC-MS). The testosterone was extracted from plasma
      using home-made Extrelut columns and diethyl ether elution. It was quantified as
      the pentafluoropropionate (PFP) derivative by selected-ion monitoring at m/z 560
      (testosterone) and 563 (d3-testosterone), accounting for about 34% of the total
      ion. The characteristics of the method were: extraction recovery about 95%;
      linearity over the range 1.7-71.5 nmol l-1 with linear regression equation y =
      1.41x + 0.0217, r = 0.999; detection limit 3.5 fmol injected with a signal-to
      noise ratio of 7.4; within-day variation, 3% for GC-MS, and 5.8% for the whole
      process; day-to-day coefficient of variation, 6.6-11%, depending on the
      concentrations. There was a good correlation between the results obtained by GC
      MS and RIA (r = 0.994), but the GC-MS values were significantly lower (p < 0.05)
      than those obtained by RIA.

PMID- 7735466
TI  - Determination of 3-methoxy-4-hydroxyphenylethylene glycol in urine using reversed
      phase liquid chromatography with column switching and electrochemical detection.
AB  - A column-switching method was developed for the determination of total 3-methoxy
      4-hydroxy-phenylethyleneglycol (MHPG) in urine. This was performed by first
      treating samples with beta-glucuronidase, followed by extraction with ethyl
      acetate. The reconstituted extracts were injected onto an HPLC system containing
      an amperometric detector and tandem Nucleosil C18 and C8 reversed-phase columns
      connected by a switching valve. The total analysis time for MHPG was 12 min. The
      limit of detection was 0.18 ng, or 9 micrograms/l for 20-microliters injections
      of a 1.0-ml reconstituted extract prepared from 1.0 ml of urine. The linear range
      extended up to 80 mg/l. The within-day precision for a urine sample containing
      170 micrograms/l total MHPG was +/- 6% and the day-to-day precision was +/- 15%.
      The average levels determined by this method for total MHPG in normal subjects
      showed good agreement with previous literature values. This approach could be
      modified for the determination of free MHPG by using only ethyl acetate
      extraction for sample pretreatment.

PMID- 7735467
TI  - Rapid determination of phenylalanine and its related compounds in rumen fluid by
      high-performance liquid chromatography.
AB  - A rapid method for the determination of phenylalanine (Phe), tyrosine (Tyr),
      benzoic acid (BZA), phenylacetic acid (PAA), phenyllactic acid (PLA),
      phenylpyruvic acid (PPY), phenylpropionic acid (PPR), and cinnamic acid (CNM) in
      goat rumen fluid was established by high-performance liquid chromatography
      (HPLC). The mobile phase used for isocratic elution was methanol-sodium acetate
      buffer (pH 6.5) (8:92, v/v). The compounds were monitored at 220 nm with a UV
      detector. A 5-microliters portion of the filtrated rumen fluid was analyzed and
      the analysis was completed within 20 min. The minimum detectable limits (microM)
      of these compounds were: 12 for Phe, 3 for Tyr, 3 for BZA, 9 for PAA, 12 for PLA,
      15 for PPY, 20 for PPR, and 8 for CNM. The average contents of Phe, BZA, PAA,
      PLA, and PPR in the rumen fluid of three goats were 15.4, 73.7, 615.9, 51.1, and
      39.9 microM before morning feeding, 17.0, 123.7, 650.4, 208.2, and 502.4 microM
      at 3 h after feeding, and 18.4, 124.2, 510.0, 129.9, and 178.5 microM at 6 h
      after feeding, respectively. Of these compounds PAA was present at the highest
      concentration both before and after feeding. The content of PPR extremely
      increased especially at 3 h after feeding. The other three compounds, i.e. Tyr,
      PPY, and CNM, were not detected in goat rumen fluid.

PMID- 7735468
TI  - Determination of 4,4'-methylenediphenyldianiline (MDA) and identification of
      isomers in technical-grade MDA in hydrolysed plasma and urine from workers
      exposed to methylene diphenyldiisocyanate by gas chromatography-mass
      spectrometry.
AB  - Gas chromatography-mass spectrometry using chemical ionization with ammonia as
      reagent gas monitoring both positive and negative ions was applied. Negative-ion
      monitoring using ammonia and the pentafluoropropionic anhydride (PFPA)
      derivatives were chosen owing to low detection limits and good separation for the
      isomers studied. Technical-grade methylenediphenyldiioscyanate (MDI) was analysed
      and three isomers, 4,4'-, 2.4'- and 2,2'-methylenediphenyldianiline (MDA), were
      determined in addition to methylated MDA. Plasma and urine from an exposed worker
      were hydrolysed and analysed and the MDA isomers were identified in the
      biological samples.

PMID- 7735469
TI  - Purification of Treponema pallidum, Nichols strain, by two-step column
      chromatography.
AB  - A rapid and simple purification method for Treponema pallidum, Nichols strain,
      the etiological agent of venereal syphilis, was developed. A 40-ml suspension of
      organisms (1.10(9)/ml) was extracted from rabbit testicular tissue and
      solubilized with a non-ionic detergent, 1-O-n-octyl-beta-D-glucopyranoside.
      Solubilized antigens were purified by cation-exchange and hydroxyapatite column
      chromatography. The overall recovery of immunoreactive material was 48.3% and the
      specific activity increased. Sodium dodecyl sulphate polyacrylamide gel
      electrophoresis and immunoblotting analysis confirmed the purity and species
      specificity of the purified antigen.

PMID- 7735470
TI  - Analysis of common opiates and heroin metabolites in urine by high-performance
      liquid chromatography.
AB  - A separation of heroin, 6-monoacetylmorphine, codeine, pholcodine, dihydrocodeine
      and morphine using a 200 x 2 mm I.D., 3 microns silica column with
      dichloromethane-pentane-diethylamine-methanol mobile phase is described. Data on
      the determination of these compounds in a urine matrix based on this separation
      using a solid-phase pretreatment with Bond Elut Certify cartridges and nalorphine
      as an internal standard are shown. The compounds listed can be quantified at
      levels below that generally accepted as the cut-off level for the screening for
      opiates by enzyme immunoassay (EMIT) with detection limits for the different
      opiates ranging from 4 to 20 ng ml-1. Comparative data are shown of subject urine
      samples assayed for opiates by both the enzyme immunoassay and the proposed
      method. The utility of the method for the elimination of so-called false
      positives detected by EMIT due to the presence of medically prescribed and non
      prescription opiates in urine is discussed.

PMID- 7735471
TI  - Improved amphetamine and methamphetamine determination in urine by normal-phase
      high-performance liquid chromatography with sodium 1,2-naphthoquinone 4
      sulphonate as derivatizing agent and solid-phase extraction for sample clean-up.
AB  - Solid-phase extraction techniques were evaluated for the treatment of urine
      samples in the analysis of amphetamine and methamphetamine by normal-phase high
      performance liquid chromatography with 1,2-naphthoquinone 4-sulphonate. Six
      different packing materials were tested, and the results obtained are compared
      with those obtained in a classical liquid-liquid extraction with n-hexane.
      Different clean-up eluents and the influence of pH of urine have been tested. The
      intra-day and inter-day precision, the accuracy of the method and the addition of
      beta-phenylethylamine as internal standard were also studied.

PMID- 7735472
TI  - Determination of serum aluminium using an ion-pair reversed-phase high
      performance liquid chromatographic-fluorimetric system with lumogallion.
AB  - An ion-pair reversed-phase high-performance liquid chromatographic method with
      fluorimetric detection, using lumogallion [4-chloro-3-(2,4-dihydroxyphenylazo)-2
      hydroxybenzene-1-sulphonic acid] as a ligand, has been successfully applied to
      the determination of aluminium in human serum. The highly fluorescent aluminium
      lumogallion complex (lambda ex 505 nm, lambda em 574 nm) was separated on a
      LiChrosorb RP-18 column with an eluent consisting of 30% acetonitrile, 70% 0.02 M
      potassium hydrogen phthalate and 10 microM lumogallion. The proposed system
      offers a simple, rapid, selective and sensitive method for the determination of
      aluminium in serum. The detection limit for aluminium was 0.05 microgram/l in
      aqueous solution and the limit of determination was 2.2 micrograms/l in serum.
      The recovery of the method is generally over 90%.

PMID- 7735473
TI  - Determination of methyleugenol in rodent plasma by high-performance liquid
      chromatography.
AB  - A method has been developed and validated for the analysis of methyleugenol, a
      volatile flavoring agent, in rodent plasma at concentrations from 0.050 to 10.0
      micrograms/ml. The method involves the addition of acetonitrile to the plasma,
      removal of the protein precipitate, and analysis of the supernatant by reversed
      phase (C18) HPLC using an acetonitrile-water mixture with UV detection. The
      precision, accuracy, sensitivity, and specificity of the method were assessed.
      The stability of methyleugenol in plasma, during freeze-thaw cycles, refrigerated
      at the extract stage, and during the analysis was evaluated. The recovery of
      methyleugenol from plasma was also determined. This method was found to be
      acceptable for plasma concentrations in toxicokinetic studies of methyleugenol in
      rodents. Over 400 samples from toxicokinetic studies have been successfully
      analyzed to date. Kinetic data from a preliminary single administration
      intravenous and oral study in rats is also presented.

PMID- 7735474
TI  - Determination of flumazenil in plasma by gas chromatography-negative ion chemical
      ionization mass spectrometry.
AB  - A gas chromatographic-negative ion chemical ionization mass spectrometric (GC-NCI
      MS) method for the determination of flumazenil in plasma is described. The GC of
      flumazenil (M(r) 303) is considered to be difficult as it is readily adsorbed in
      the GC column. Therefore, preconditioning the GC column with reconstituted
      extract from plasma and Silyl-8 was required to cover the active sites on the
      column. Monitoring the maximum mass peak (m/z 275) of the flumazenil resulted in
      a tenfold enhancement of sensitivity and signal-to-noise ratio (concentration = 1
      ng/ml). Isotopically labeled flumazenil-d3 (M(r) 306, m/z 278) was used as the
      internal standard. The detection limit for flumazenil was found to be 0.1 ng/ml
      with an injection volume of 2 microliters. The signal-to-noise ratio was about
      10. The routine quantification limit was set at 2 ng/ml for dog plasma and 1
      ng/ml for human plasma. The sample volumes in both instances were 1 ml.

PMID- 7735475
TI  - Determination of the acylcoenzyme A cholesterol acyltransferase inhibitor 447C88
      in plasma using gas chromatography-mass spectrometry and liquid chromatography
      atmospheric pressure chemical ionisation tandem mass spectrometry.
AB  - Two mass spectrometry-based methods are described for the determination of 447C88
      (I), a novel inhibitor of acylcoenzyme A cholesterol acyltransferase (ACAT), in
      rat, dog and human plasma. The first method uses gas chromatography-mass
      spectrometry (GC-MS) with electron ionisation and selected-ion monitoring. The
      method employs solid-phase extraction of I from plasma and requires alkylation of
      I using iodoethane. The second method uses liquid chromatography-tandem mass
      spectrometry (LC-MS-MS) with atmospheric-pressure chemical-ionisation and
      selected-reaction monitoring. The LC-MS-MS method uses a simplified version of
      the extraction procedure used for GC-MS and does not require derivatisation of I.
      While both methods provide the necessary limit of quantitation of 0.5 ng/ml in
      human, dog and rat plasma with the required precision and accuracy, the LC-MS-MS
      assay offers increased sensitivity, selectivity and speed over the GC-MS assay.
      This allows a same day turn round of results for in excess of 100 samples,
      including sample preparation and data acquisition and processing.

PMID- 7735476
TI  - Megabore capillary gas-liquid chromatographic method with nitrogen-phosphorus
      selective detection for the assay of haloperidol and reduced haloperidol in
      serum: results of therapeutic drug-monitoring during acute therapy of eight
      schizophrenics.
AB  - A gas chromatographic method using a HP-5 megabore capillary and nitrogen
      phosphorus selective detection for the quantitative analysis of haloperidol (H)
      and reduced haloperidol (RH) in human serum or plasma is described. A 3-step
      liquid-liquid extraction is applied. The extraction yield of this procedure is
      63% for haloperidol at 20 ng/ml. The limits of detection are 0.4 ng/ml for
      haloperidol and 1.0 ng/ml for the metabolite if 2 ml of body fluid are applied.
      At 10 ng/ml the within-day precision is 4.5% for H and 8.3% for RH. Serum levels
      of eight schizophrenic patients have been monitored weekly over a therapeutic
      period of six weeks. Seven patients mainly had metabolite ratios RH/H < 1 over
      the entire period of investigation. They exhibited a linear correlation between
      dose and serum concentration of haloperidol. In contrast, one patient had
      metabolite ratios RH/H > 1 over the entire period of the study. Due to
      considerable increased serum concentrations this patient did not show a linear
      correlation between the dose and the serum level of haloperidol.

PMID- 7735477
TI  - High-performance liquid chromatographic assays with fluorometric detection for
      mivacurium isomers and their metabolites in human plasma.
AB  - Two high-performance liquid chromatographic assays coupled with fluorometric
      detection have been developed for the determination of mivacurium isomers (trans
      trans, cis-trans and cis-cis) and their monoester and alcohol metabolites in
      human plasma. A novel solid-phase extraction procedure allowed good recovery of
      the mivacurium isomers (mean 98%) and their monoester metabolites (mean 83%),
      whereas the alcohol metabolites were analyzed after direct precipitation of
      plasma proteins. For all analytes, these assays proved to be sensitive (LOQ 3.9
      15.6 ng/ml), reproducible (C.V. < 15%) and accurate (> 94%) over the therapeutic
      range of concentrations of mivacurium and its metabolites. These two methods were
      applied successfully to a pharmacokinetic study of mivacurium after a bolus dose
      of 0.15 mg/kg in anesthetized patients.

PMID- 7735478
TI  - High-performance liquid chromatographic determination of terguride in solid
      dosage forms and plasma.
AB  - A simple and rapid HPLC method was developed to determine terguride in terguride
      hydrogenmaleate, coated tablets and plasma. The assay was carried out on a glass
      column of SGX CN (150 x 3.3 mm I.D.) using methanol and phosphate buffer solution
      (pH 7.0) as the mobile phase, with detection at 227 nm. Terguride was quantified
      using promethazine as an internal standard. The tablet matrix was extracted into
      methanol. Plasma samples were deproteinated with acetonitrile and the supernatant
      was injected into the HPLC system. The method is linear, quantitative and
      reproducible.

PMID- 7735479
TI  - Determination of the stereoselective aspects in in-vitro and in-vivo metabolism
      of the analgesic meptazinol by high-performance liquid chromatography.
AB  - A reversed-phase high-performance liquid chromatographic method to separate
      meptazinol and its phase I metabolites has been developed using a LiChrosper 100
      CN column and a mobile phase of trimethylammoniumacetate buffer (pH 5.5)
      acetonitrile-methanol. Quantification of meptazinol and N-desmethylmeptazinol in
      biological samples was achieved by extraction with organic solvents and
      chromatographic analysis (detection limit 0.4 and 0.25 micrograms/ml,
      respectively). Afterwards the enantiomeric ratio of the two compounds was
      determined on a Chiral AGP column with a mobile phase of phosphate buffer (pH
      7.0)-acetonitrile (alpha = 1.29 and 1.49, respectively). In-vitro metabolism data
      after incubation of the racemic compound and the enantiomers with liver
      supernatant and microsomes of different species are presented. Finally urinary
      data of two volunteers after oral application of the racemic drug were
      determined.

PMID- 7735480
TI  - Measurement of 5,10-dideaza-5,6,7,8-tetrahydrofolate (lometrexol) in human plasma
      and urine by high-performance liquid chromatography.
AB  - Three high-performance liquid chromatographic methods are described for the
      detection of the novel antifolate anticancer drug (6R)-5,10-dideaza-5,6,7,8
      tetrahydrofolate (lometrexol): one with fluorometric detection and two with
      detection by UV absorbance. An assay for plasma lometrexol using UV detection
      (288 nm) and reversed-phase chromatography was developed, with a quantitation
      limit of 0.2 microgram/ml and linearity up to 10 micrograms/ml. This assay was
      modified for measurement of lometrexol in urine, with a quantitation limit of 2
      micrograms/ml and linearity up to 25 micrograms/ml. An alternative assay for
      plasma lometrexol using derivatization and fluorescence detection (excitation at
      325 nm, emission at 450 nm) was also developed, which proved twenty-fold more
      sensitive (quantitation limit of 10 ng/ml) than the UV assay, and which was
      linear up to 250 ng/ml. The fluorometric method requires sample oxidation with
      manganese dioxide prior to analysis, and uses ion-pair chromatography with
      tetramethylammonium hydrogensulphate as an ion-pair reagent. All assays use a
      similar preliminary solid-phase extraction method (recovery as assessed by UV
      absorption > 73%), with C10-desmethylene lometrexol added for internal
      standardisation. Each assay is highly reproducible (inter-assay precision in each
      assay is < 10%). Applicability of the fluorescence-based assay to lometrexol in
      plasma and the UV-based assay to lometrexol in urine is demonstrated by
      pharmacokinetic studies in patients treated as part of a Phase I clinical
      evaluation of the drug.

PMID- 7735481
TI  - Isocratic high-performance liquid chromatographic assay of taxol in biological
      fluids and tissues using automated column switching.
AB  - This report describes the analysis of taxol in human plasma, cell culture medium,
      and dog bladder tissue by isocratic high-performance liquid chromatography (HPLC)
      with automated column switching. Cephalomannine was used as the internal
      standard. Biological samples were extracted with ethyl acetate, with a recovery
      of > 80%. Sample extracts reconstituted in 37.5% acetonitrile were stable in
      polypropylene tubes at room temperature for 22 h. The HPLC stationary phase
      consisted of a clean-up column (Nova-Pak C8, 75 x 3.9 mm I.D., 4 microns particle
      size) and an analytical column (Bakerbond octadecyl, 250 x 4.6 mm I.D., 5 microns
      particle size). Taxol and cephalomannine were monitored at 229 nm. Samples were
      injected onto the clean-up column and eluted with the clean-up mobile phase
      (37.5% acetonitrile in distilled water) at 1 ml/min. Concurrently, the analytical
      mobile phase (49% acetonitrile in distilled water) was directed through the
      analytical column at a flow-rate of 1.2 ml/min. A heart-cut fraction from 8 to 15
      min was transferred from the clean-up column onto the analytical column. Loading
      of a second sample onto the clean up column while the first sample was eluting
      from the analytical column reduced the HPLC analysis time to about 15 min per
      sample. This method has a lower detection limit of 5 ng/ml and intra- and inter
      day variations of < 5%.

PMID- 7735482
TI  - High-performance liquid chromatographic determination of the antifungal drug
      fluconazole in plasma and saliva of human immunodeficiency virus-infected
      patients.
AB  - A high-performance liquid chromatographic (HPLC) assay has been developed for the
      determination of the antifungal drug fluconazole in saliva and plasma of patients
      infected with the human immunodeficiency virus (HIV). Samples can be heated at 60
      degrees C for 30 min to inactivate the virus without loss of the analyte. The
      sample pretreatment involves a liquid-liquid extraction with chloroform-1
      propanol (4:1, v/v). The chromatographic analysis is performed on a Lichrosorb RP
      18 (5 microns) column by isocratic elution with a mobile phase of 0.01 M acetate
      buffer (pH 5.0)-methanol (70:30, v/v) and ultraviolet (UV) detection at 261 nm.
      The lower limit of is 100 ng/ml in plasma (using 500-microliters samples) and 1
      microgram/ml in saliva (using 250-microliters samples) and the method is linear
      up to 100 micrograms/ml in plasma and saliva. At a concentration of 5
      micrograms/ml the within-day and between-day precision in plasma are 7.1 and
      5.7%, respectively. In saliva the within-day and between-day precision is 10.8%
      (at 5 micrograms/ml). The methodology is now being used in pharmacokinetic
      studies in HIV-infected patients in our hospital.

PMID- 7735483
TI  - Determination of terbinafine and its desmethyl metabolite in human plasma by high
      performance liquid chromatography.
AB  - A reliable reversed-phase high-performance liquid chromatographic method has been
      developed for the determination of terbinafine (Terb) and its desmethyl
      metabolite (DMT) in human plasma. The analytes and the internal standard (I.S.)
      are extracted by a liquid-liquid technique followed by an aqueous back
      extraction, allowing injection of an aqueous solvent in the HPLC system. The
      mobile phase is acetonitrile + 0.012 M triethylamine -0.020 M orthophosphoric
      acid (50:50, v/v) and the UV detection is at 224 nm. The inter-assay precision
      over the concentration range 2-1000 ng/ml is between 2.9 and 9.8% for both
      compounds. The limit of quantification, 2 ng/ml for both compounds, is sufficient
      for investigating the pharmacokinetics of Lamisil in human studies. With an
      additional preparation step, this method can be used for assaying Terb in tissues
      such as nail, sebum and stratum corneum.

PMID- 7735484
TI  - Quantification of an 11C-labelled beta-adrenoceptor ligand, S-(-)CGP 12177, in
      plasma of humans and rats.
AB  - beta-Adrenoceptors in human lungs and heart can be imaged with the radioligand 4
      [3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3- dihydro-2H-benzimidazol-2
      11C-one (CGP 12177, [11C]I). For quantification of receptor density with
      compartment models by adjustment of rate constants, an 'input function' is
      required which consists of the integral of the concentration of unmodified ligand
      in arterial plasma over time. A discrepancy in the literature regarding metabolic
      stability of [11C]I prompted us to study metabolism in rats by reversed-phase
      HPLC (RP-HPLC) of trichloroacetic acid extracts of arterial plasma after i.v.
      injection of [11C]I (> 11.1 TBq/mmol, 11 MBq/kg). Some plasma samples were also
      directly applied to an internal-surface reversed-phase (ISRP) column. In parallel
      experiments, tritiated [11C]I was employed and methanol extracts of arterial
      plasma were analyzed by straight-phase TLC. The three methods were in excellent
      agreement. Unmodified [11C]I decreased from > 98.5% (3H) or > 99.9% (11C)
      initially to 57 +/- 7% at 80 min post injection due to formation of two polar
      metabolites. Using the RP-HPLC method, no metabolism was detectable in humans up
      to 30 min after injection of [11C]I (1851 MBq). Deproteinization of plasma with
      acetonitrile resulted in the formation of a radioactive species (artifact) which
      eluted immediately after the void volume in RP-HPLC and which could be mistakenly
      interpreted as a metabolite. Plasma protein binding was low (ca. 30%) in both
      humans and rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735485
TI  - Determination of free and total 7-hydroxycoumarin in urine and serum by capillary
      electrophoresis.
AB  - A new method for the rapid determination of 7-hydroxycoumarin, the predominant
      metabolite of coumarin in humans, was developed for analysis in urine and serum,
      based on separation by capillary electrophoresis, with UV detection at 210 nm.
      The linear detection range for 7-hydroxycoumarin was 0-50 micrograms/ml while the
      limit of quantitation was 1 microgram/ml. An internal standard, 3-(alpha
      acetonylbenzyl)-4-hydroxycoumarin, was utilised for the determination of free 7
      hydroxycoumarin, but it was found not to be suitable in the analysis of total 7
      hydroxycoumarin present. Urine from two volunteers, who had been administered
      coumarin, was analysed by both capillary electrophoresis and by HPLC. The results
      from the two methods were compared and contrasted. The CE method was found to
      decrease the analysis time in comparison to HPLC analysis, with results available
      after 1.5 min as compared to 12 min with HPLC. There was no statistical
      difference between the results determined by either method.

PMID- 7735486
TI  - Sensitive high-performance liquid chromatographic assay for norfloxacin utilizing
      fluorescence detection.
AB  - A rapid, sensitive and reproducible reversed-phase high-performance liquid
      chromatographic assay was developed for the determination of norfloxacin.
      Following protein precipitation with 10% trichloroacetic acid, norfloxacin and
      the internal standard enoxacin were extracted from plasma with chloroform, dried
      and reconstituted in the mobile phase. The chromatographic separation of
      norfloxacin and the internal standard enoxacin was achieved on a C8 column with
      fluorescence detection set at 280 and 418 nm for excitation and emission,
      respectively. The peaks with a resolution factor greater than 1.5 were free from
      interferences. Excellent linearity (r2 > or = 0.998) was observed over the
      concentration range 0.025-5.0 micrograms/ml in plasma. The inter-assay
      variability was 13.6% or less at all concentrations examined. The suitability of
      the assay for pharmacokinetic studies was determined by measuring norfloxacin
      concentration in rat plasma after administration of a single intravenous 10 mg/kg
      dose.

PMID- 7735487
TI  - Determination of piracetam in human plasma and urine by liquid chromatography.
AB  - A method for the determination of piracetam in human plasma and urine by liquid
      chromatography with absorbance detection at 206 nm and isocratic elution is
      proposed. The assay involved a liquid-liquid extraction into hexane-2-propanol at
      pH 9.2. The calibration graphs were linear in the range 3-40 mg/l in plasma and
      100-2000 mg/l in urine. Bias was negligible and coefficients of variation were
      less than 10% throughout the working range except at 100 mg/l in urine. The
      limits of quantification were 3 mg/l in plasma and 100 mg/l in urine. The assay
      was reliably used for pharmacokinetic studies in humans after administration of
      800 mg of piracetam per os.

PMID- 7735488
TI  - Determination of vinorelbine in rabbit plasma by high-performance liquid
      chromatography with coulometric detection.
AB  - A high-performance liquid chromatographic method was developed for the
      determination in plasma (400-microliters sample) of a vinca alkaloid,
      vinorelbine. The analysis was performed by using an octadecylsilane column and
      heptanesulfonic acid as ion-pairing agent. This method used a new internal
      standard, teniposide, that permitted a good compromise between sensitivity and
      retention times (10.6 and 15.5 min for teniposide and vinorelbine, respectively).
      After a liquid-liquid extraction with diethyl ether, the extracts were injected
      into a reversed-phase system. The extraction efficiency was approximately 80% for
      both vinorelbine and the internal standard. The mobile phase was phosphate buffer
      (pH 3)-acetonitrile-methanol (50:30:20, v/v/v). Using coulometric detection, the
      limit of detection in plasma (400 microliters) was 1 ng/ml. The intra-assay
      coefficients of variation were 10.95, 3.80 and 5.71% for 5, 500 and 1000 ng/ml,
      respectively, and the inter-assay coefficients of variation were 20.14, 14.27 and
      10.67% for 5, 500 and 1000 ng/ml, respectively. A linear response was observed
      for the plasma calibration graph in the ranges 2.5-50 and 50-1000 ng/ml. This
      method was used to follow the time course of the concentration of vinorelbine in
      rabbit plasma after a single intravenous dose of vinorelbine (30 mg/m2) and seems
      to be suitable for studying the pharmacokinetics of vinorelbine in rabbit.

PMID- 7735489
TI  - Measurement of 4-hydroxycyclophosphamide in serum by reversed-phase high
      performance liquid chromatography.
AB  - A reversed-phase high-performance liquid chromatographic method was developed for
      the measurement of 4-hydroxycyclophosphamide (4-OH-CP) in human serum, since no
      such assay has been described to date. In the present procedure, the serum sample
      was treated with semicarbazide at pH 7.4 to derivatize the 4-OH-CP to its
      aldophosphamide semicarbazone form. Derivatization was performed at 60 degrees C
      for 60 min and the product was extracted with ethyl acetate-chloroform (75:25,
      v/v). The derivatives formed were chromatographed on a C8 reversed-phase column
      with a mobile phase of 0.025 M phosphate buffer-acetonitrile (18:82, v/v) and a
      detection wavelength of 230 nm. The limit of detection of the assay was 0.025
      mg/l for 1 ml of serum with a signal-to-noise ratio of 2. The between-assay
      coefficients of variation at concentrations of 0.2 and 0.4 mg/l were 7.7 and 7.0%
      respectively. The simplicity and specificity of this method make it directly
      applicable to clinical studies on 4-OH-CP pharmacokinetics.

PMID- 7735490
TI  - Sodium dodecyl sulfate solution is an effective between-run rinse for capillary
      electrophoresis of samples in biological matrices.
AB  - It is common practice in capillary electrophoresis to perform some sort of
      capillary washing step(s) between separations. In many analyses little
      consideration is given to optimization of the wash, and typically a rather
      standard washing procedure is used involving a few minutes wash with 0.1 M NaOH
      followed by a few minutes reconditioning with the run buffer. As an alternative
      to this procedure, we have investigated the use of wash solutions containing
      sodium dodecyl sulfate (SDS). This type of wash has been used in the analyses of
      both small molecules and proteins, with encouraging results. After the SDS wash,
      the electroosmotic flow has been shown to be restored to values close to normal
      in a capillary which had previously been coated with plasma proteins. Separation
      efficiency for a test compound (dextromethorphan) is improved if an SDS rather
      than a HCl-NaOH wash is used after injection of plasma. In a direct-injection
      analysis of plasma proteins using a pH 10 borate buffer, an SDS-based washing
      procedure (total time, 1 min) gave better migration-time reproducibility than an
      NaOH-based wash, which took 5 min in total.

PMID- 7735491
TI  - Body weight and fat cell size in young men with mild blood pressure elevation.
AB  - The aim of the study was to assess the relationship between body fat distribution
      and blood pressure. Forty-four men, aged 19-22 years, with mild blood pressure
      elevation (MBPE) and 29 normotensive controls (NC) were investigated. Body fat
      distribution was assessed by calculating fat cell size in biopsy samples of
      adipose tissue from different subcutaneous depots. The subjects in MBPE group
      were heavier than those in NC group (79.7 +/- 2.7 and 71.5 +/- 1.6 kg, p < 0.05).
      Total body fat was also significantly higher in the MBPE group (12.5 +/- 1.6 and
      8.1 +/- 1.3 kg, p < 0.05) but not the lean body cell mass (36.8 +/- 1.1 and 34.7
      +/- 0.9 kg, n.s.). Fat cell size (microgram/cell) in the lower abdominal area
      were significantly bigger in MBPE than in NC (respectively 40.9 +/- 4.4 and 28.0
      +/- 3.1, p < 0.05). The same differences applied for fat cell size in the upper
      abdominal (respectively 43.1 +/- 3.0 and 26.8 +/- 3.0, p < 0.001) and averaged
      abdominal areas (respectively 40.1 +/- 3.4 and 26.8 +/- 2.8; p < 0.05). Fat cell
      size in gluteal, femoral and averaged gluteofemoral areas did not differ between
      MBPE and NC. Therefore, the abdominal/gluteofemoral ratio was significantly
      higher in MBPE than in NC (respectively 1.1 +/- 0.1 and 0.7 +/- 0.1; p <
      0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735492
TI  - The Bergen Blood Pressure Study: prehypertensive changes in cardiac structure and
      function in offspring of hypertensive families.
AB  - Cardiac morphology and function were determined by echocardiography in
      normotensive offspring of 23 hypertensive and 22 normotensive families. The
      family histories of hypertension or normotension were based on 27 years'
      observation of parental blood pressure. Pulsed Doppler and M-mode
      echocardiography were performed in standard views. Out of the total 109
      offspring, 94 participated in the present study (age (mean +/- SD) 36 +/- 7
      years). Left ventricular posterior wall thickness was higher in offspring of
      hypertensive than normotensive families (10.1 +/- 1.7 vs. 9.3 +/- 1.5 mm; p <
      0.05). Offspring of hypertensive families had lower transmitral early/late peak
      flow velocities (p < 0.001) and higher transmitral late peak flow velocities (p <
      0.001) than offspring of normotensive families, but the differences between
      groups became inconsistent after adjustment for confounding variables (including
      left ventricular structural parameters). On the other hand, the family history of
      hypertension was consistently associated with increased transmitral early peak
      flow velocity and increased transmitral acceleration and deceleration slopes p <
      0.05), a pattern suggesting increased left ventricular stiffness. Increased
      posterior wall thickness and diastolic functional changes may indicate cardiac
      hypertrophy and decreased left ventricular compliance and precede the development
      of hypertension in offspring of hypertensive families.

PMID- 7735493
TI  - Left ventricular contractility and insulin resistance in essential hypertension.
AB  - The relationship between fasting insulin as well as the insulin response to an
      oral glucose tolerance test and echocardiographic cardiac geometry and function
      was assessed in 55 never-treated lean patients with essential hypertension and
      normal glucose tolerance and 31 age- and gender-matched normal subjects. The
      ratio of the area under the curve of the response of insulin and glucose to the
      oral glucose load was positively correlated with supine heart rate (r values of
      0.37) or left ventricular contractility estimated by the end-systolic wall stress
      to end-systolic volume index ratio and the afterload-corrected fractional
      shortening (r = 0.59 and 0.36, respectively). No correlation between insulin and
      left ventricular mass index was observed. When hypertensive patients were divided
      into those without (n = 39) and with insulin resistance (n = 16), as defined by
      an elevated value of the ratio of the area under the curve of the response of
      insulin and glucose, it appeared that both heart rate, end-systolic wall stress
      to end-systolic volume index ratio and afterload-corrected fractional shortening
      were higher in patients with insulin resistance, whereas age, arterial pressure,
      left ventricular mass index, urinary electrolytes, and plasma renin activity were
      similar in the two groups. These results suggest that increased cardiac systolic
      performance and heart rate may be associated with insulin resistance in a subset
      of lean patients with never-treated essential hypertension.

PMID- 7735494
TI  - The Bergen Blood Pressure Study revisited.

PMID- 7735495
TI  - Unchanged central hemodynamics after six months of moderate sodium restriction
      with or without potassium supplement in essential hypertension.
AB  - Sodium (Na) restriction and potassium (K) supplementation has been recommended as
      treatment of essential hypertension but the mechanism by which these may reduce
      blood pressure (BP) is unknown. We examined if moderately reduced Na intake,
      combined with a low-Na/high-K salt alternative (Pansalt: NaCl 57%, KCl 28%, MgSO4
      12%) as substitute for standard table salt, induced clinically significant BP
      reduction in hypertensive patients and, if this therapy reduced total peripheral
      resistance. After a 2-month control period 40 patients aged 21-67 years with mean
      casual BP 156/103 mmHg were given a salt restricted diet (120 mmol Na/24 h) for 6
      months. In addition, they were randomised in a double-blind manner to receive
      either Pansalt (P-group) or standard NaCl (S-group) as table salt in small
      amounts. Cardiac output was measured by dye dilution. Daily Na excretion was
      similarly reduced (20%) in both groups while K excretion was slightly increased
      in the P-group and reduced in the S-group (difference p < 0.05). No large changes
      occurred in 24-h ambulatory BP (by Accutracker II) or intraarterial pressure
      (through a brachial artery catheter) at rest or during exercise while casual BP
      was reduced (p < 0.05) 13/8 mmHg in the P-group and 8/5 mmHg in the S-group.
      While cardiac output was slightly reduced at rest and during 50W exercise in the
      P-group, no significant changes were seen in total peripheral resistance in
      either group. Thus, moderate reduction in Na intake, with or without addition of
      K, is not sufficient to induce significant long-term intraarterial or 24-h
      ambulatory BP changes in essential hypertension. Without BP changes invasively
      determined central hemodynamics remains remarkably stable over a 6-month period.

PMID- 7735496
TI  - Structural changes in the cardiovascular system of untreated essential
      hypertensives.
AB  - Arterial hypertension is associated with structural changes in the cardiovascular
      system. This study has examined the effect of hypertension on the carotid artery
      wall and examined the relation between changes in the structure of carotid artery
      wall and left ventricle in untreated hypertensives. The carotid artery wall was
      visualized using a high resolution ultrasound technique in 37 untreated
      hypertensive patients (25 males, 12 females) and 37 age and sex matched
      normotensive individuals and carotid intima-media thickness (IMT) and carotid
      artery diameter measured. IMT and intima-media cross sectional area was
      significantly greater in the hypertensive group compared with the normotensive
      group, though the carotid artery diameter did not differ significantly. There was
      a significant association between age and IMT in both groups. In the hypertensive
      group there was also a significant association between left ventricular mass
      index, ventricular septal or posterior wall thickness and IMT. This study
      indicates that there is an association between cardiac and carotid arterial
      structure in hypertension. Such a relationship may be important in understanding
      the associated risks of high blood pressure.

PMID- 7735497
TI  - Aortic distensibility in normotensive, untreated and treated hypertensive
      patients.
AB  - BACKGROUND: Compared with normotensive subjects, untreated hypertensive patients
      show a decrease of their aortic distensibility. Whether antihypertensive
      treatment, by reducing blood pressure and changing functional and/or structural
      abnormalities of the arterial wall, may prevent or reverse the arterial damage
      due to the accelerated ageing process remains unclear. The objective of the
      present study was to determine, using a cross-sectional approach, whether aortic
      distensibility as measured by pulse wave velocity, in treated hypertensive
      patients whose diastolic blood pressure had been normalised for several months,
      was significantly improved over that of untreated hypertensive patients. METHODS:
      Carotid femoral pulse wave velocity was measured in 124 normotensive subjects and
      388 hypertensive patients. The latter group included 164 treated patients with
      well controlled diastolic blood pressure and 224 untreated hypertensive subjects.
      The three groups did not differ in other cardiovascular risk factors. RESULTS: In
      each group there was a significant relationship between age and pulse wave
      velocity. When compared with untreated hypertensives, treated hypertensives with
      well controlled diastolic blood pressure had significantly lower blood pressure
      and pulse wave velocity according to age. However, although diastolic blood
      pressure of well controlled hypertensives was not significantly different from
      that of normotensive subjects, the aortic distensibility of the controlled
      hypertensives remained reduced showing two characteristics: a faster increase in
      pulse wave velocity with age and a negative relationship with HDL-cholesterol.
      CONCLUSION: These results suggest that long-term antihypertensive treatment and
      control of blood pressure using only diastolic blood pressure criteria may not
      fully reverse arterial alteration associated with hypertensive vascular disease.

PMID- 7735498
TI  - Blood pressure variability and its implications for antihypertensive therapy.
AB  - Although it is clear that antihypertensive treatment is beneficial in reducing
      stroke morbidity and mortality, the results of the major outcome studies show
      less impact on coronary heart disease. Studies utilizing 24-h blood pressure (BP)
      monitoring show a positive association between target organ damage and the level
      of 24-h BP, and with variability in BP, which is an independent determinant of
      target organ damage. Current understanding of the pathogenesis and
      pathophysiology of coronary heart disease suggests that optimal antihypertensive
      treatment should ensure the following: effective 24-h BP control, smooth
      antihypertensive effect with reduced variability; attenuation of the early
      morning surge in BP; maintenance of the normal circadian pattern of BP; effective
      therapeutic coverage in the face of suboptimal compliance; and lack of reflex
      activation of the sympathetic nervous system. On the basis of our current
      understanding, this optimum is most likely to be achieved by the use of
      antihypertensive agents with a long duration of action.

PMID- 7735499
TI  - Cardiovascular effects of microinjection of corticoids and antagonists into the
      rostral ventrolateral medulla in rats.
AB  - Experiments were performed on Wistar or Sprague-Dawley rats of both sexes.
      Microinjection of corticosterone (10 or 40 ng/0.1 microliter/site) into the
      rostral ventrolateral medulla (rVLM) caused an increase in systolic blood
      pressure (SBP), heart rate (HR) and pressor response induced by stimulation of
      the dorsal periaqueductal grey (dPAG) in the midbrain. Microinjection of
      aldosterone (10 or 40 ng/0.1 microliter/site) into the rVLM had similar effects
      showing a higher level and longer period than that of corticosterone. All these
      effects were dose-dependent. Microinjection of glucocorticoid antagonist RU 38486
      (40 ng/0.1 microliter/site) or mineralocorticoid antagonist spironolactone (40
      ng/0.1 microliter/site) caused a decrease in SBP, HR and the pressor response
      induced by stimulation of the dPAG. The inhibitory effects of spironolactone were
      more apparent. These results suggest that both corticoids could exert central
      modulatory effects on the resting cardiovascular activities and facilitate the
      pressor response during a defense reaction, and the rVLM is an essential area for
      the location of the central modulation. These effects may play an important role
      in the incidence and development of hypertension induced by stress.

PMID- 7735500
TI  - The natural history of human dermatosparaxis (Ehlers-Danlos syndrome type VIIC).
AB  - Dermatosparaxis (Ehlers-Danlos syndrome type VIIC) has only recently been
      identified in human subjects. Although well documented in animals, to date only
      three human cases have been recorded, all aged 2 years or under. We document a 15
      year-old girl with this newly recognized condition to emphasize the remarkable
      similarity of physical signs in all four cases. The striking skin fragility which
      attends the phenotype is highly distinctive, so that the diagnosis may be
      suspected on clinical grounds. The confirmatory diagnostic procedures are
      discussed.

PMID- 7735501
TI  - Mandibulo-acral dysplasia: heterogeneity versus variability.
AB  - Several patients with mandibulo-acral dysplasia have been described, although it
      is becoming clear that the phenotype is quite variable, both with regards to
      clinical findings and age of onset. This is a review of the literature on
      mandibulo-acral dysplasia, as well as a discussion on variability versus
      heterogeneity in this entity.

PMID- 7735502
TI  - Trisomy 17p11-pter: unbalanced pericentric inversion, inv(17)(p11q25) in two
      patients, unbalanced translocations t(4;17)(q27;p11) in a newborn and t(4;17)
      (p16;p11.2) in a fetus.
AB  - Three patients and one fetus with almost complete trisomy 17p due to familial
      rearrangements are described. Two patients followed unbalanced transmission of a
      familial pericentric inversion, and one patient and one fetus were due to
      unbalanced segregation of familial translocations. In the inversion family,
      another two patients with multiple malformations had died before chromosome
      examination could be performed. The pattern of congenital anomalies as revealed
      from eleven cases of trisomy 17p11-pter include as the most prominent features:
      prenatal growth retardation, microcephaly, downslanting palpebral fissures, small
      mouth, small mandible, poorly shaped ears, short and webbed neck, genital
      hypoplasia, clinodactyly of fingers, crowding of toes, a high incidence of
      congenital heart defects and hernias. Postnatal survival is short mainly in
      patients with congenital heart defects. From the age of about 6 years onward,
      clinical findings become more distinct, with some signs of Charcot-Marie-Tooth
      neuropathy (pes cavus, adducted thumbs, dorsiflexed hallux, camptodactyly and
      limitation of movements in different joints), and the nose gets narrow and sharp,
      with hypoplastic alae.

PMID- 7735503
TI  - Syndromal hypothalamic hamartoblastoma with holoprosencephaly sequence,
      microphthalmia, pulmonary malformations, radial hypoplasia and mullerian
      regression: further delineation of a new syndrome?
AB  - A 24-week-old fetus is described here with holoprosencephaly sequence
      (arhinencephaly and agenesis of the corpus callosum) associated with brain and
      meningeal dysplasia, microphthalmia with an ectopic pigmentary layer,
      hypothalamic hamartoblastoma, preaxial asymmetric limb reduction, lung
      hypoplasia, gastric hypoplasia, Mullerian regression, intestinal malrotation,
      asplenia, and normal chromosomes. The differential diagnosis includes the
      Cerebroacrovisceral-Early lethality (CAVE) phenotype, and the Pallister-Hall
      syndrome, but the anomalies best fit the severe form of microgastria-limb
      reduction syndrome. Together with a previous case reported by Meinecke, the
      pattern of anomalies appears to represent a combination of defects, related to
      but distinct from the microgastria-limb reduction syndrome.

PMID- 7735504
TI  - Specific acromesomelia with facial and renal anomalies: a new syndrome.
AB  - A facio-renal-acromesomelic syndrome is reported in a 15-year-old boy with normal
      intelligence. The main dysmorphic features are a large head and congenital ptosis
      with telecanthus. There is unilateral ureteral stenosis with hydronephrosis. Bone
      abnormalities consist of ulnar dysplasia and tibial hypoplasia, multiple
      synostoses of carpal and tarsal bones, proximal synostoses of metatarsals, and of
      brachydactyly. A similar case has not been published.

PMID- 7735505
TI  - Autosomal recessive omodysplasia.

PMID- 7735506
TI  - Osteodysplastic primordial dwarfism: a case with features of type II.
AB  - We describe a 22-month-old Japanese girl with severe microcephaly with a
      prominent nose and a receding chin, developmental delay, marked intrauterine and
      postnatal dwarfism with limb shortening and brachydactyly, and distinctive
      radiological changes of the skeleton. The radiological findings include
      hypoplasia of the short tubular bones, multiple pseudoepiphyses in the bases of
      the metacarpals, coxa valga, a wide pelvis with iliac flaring, thoracolumbar
      scoliosis, and disharmonious ossification delay. The clinical and radiological
      features are somewhat different from those of previously reported cases with
      osteodysplastic primordial dwarfism. The clinical and radiological manifestations
      of osteodysplastic primordial dwarfism are reviewed and compared with those in
      our patient.

PMID- 7735507
TI  - Mulibrey nanism.
AB  - Investigation of a 4-year-old boy with 'Russell-Silver-phenotype' led to the
      relatively rare diagnosis of Mulibrey nanism. Subsequently cardiac investigation
      confirmed a constrictive pericarditis which is characteristic of this syndrome,
      although not included in the acronym (muscle, liver, brain, eye). Identification
      of this syndrome is important for genetic counselling of the parents (25%
      recurrence risk, McKusick No. 253250).

PMID- 7735508
TI  - A cognitively normal boy with meningoencephalocele, arthrogryposis and
      hypoplastic thumbs.

PMID- 7735509
TI  - Porencephaly and transverse limb defects following severe maternal trauma in
      early pregnancy.
AB  - A 13 year old boy with mental retardation, hemiatrophy and left hemiplegia, right
      hemifacial microsomia and transverse digital amputations is reported. He is
      moderately mentally retarded, experiences grand mal seizures and has evidence of
      a porencephalic cyst in the right frontotemporal region on CT scan. At 52 days
      post conception his mother was involved in a road traffic accident and suffered
      extensive bruising of the abdomen and concussion. It is suggested that the
      patient's congenital anomalies are a consequence of hypoxia and thrombo-embolic
      events sustained during early pregnancy.

PMID- 7735510
TI  - A child with oligo-syndactyly and 'apple peel' bowel atresia.
AB  - A baby with 'apple peel' jejunal atresia and limb abnormalities is described. The
      literature on 'apple peel' atresia is reviewed and the possible aetiology is
      discussed.

PMID- 7735511
TI  - 'Disorganization-like syndrome' with 47,XXY and unilateral narrowing of the
      common iliac artery.
AB  - We described a male infant with a spectrum of anomalies compatible with the
      diagnosis of 'disorganization-like syndrome'. The infant had a partial foot
      arising from the right buttock, an absent right kidney, and a shortened right leg
      with severe non-positional talipes equinovarus. The infant's karyotype was
      47,XXY. The right common iliac artery was one half of the expected diameter. The
      limb reduction defect seen in this case of disorganization (Ds) may have had a
      vascular aetiology.

PMID- 7735512
TI  - Extreme hypotrophy of the lower body pole, extensive hypoplasia of the spinal
      column and multiple anomalies of abdominal organs: a maximal variant of the
      caudal regression sequence?
AB  - A newborn with extreme hypotrophy of the lower body pole and aplasia of the lower
      spinal column is reported. Additional anomalies of internal organs included
      absence of one kidney and ureter, a diaphragmatic hernia, and anal atresia. Part
      of the organs located in the lower body pole were necrotic. There were no
      excretory apertures, and external genitalia were absent. Chromosomal analysis
      revealed a 46,XY karyotype. The multiple anomalies seen in this newborn may be
      interpreted as a maximal variant of the caudal regression sequence.

PMID- 7735513
TI  - Cord blood mononuclear leukocytes of neonates at risk of atopy have a deficiency
      of arachidonic acid.
AB  - Essential fatty acids and their delta-6-desaturated derivatives are major
      components of cellular membrane phospholipids, contributing to their stability
      and functions. They are also precursors of inflammation mediators such as
      prostaglandins and leukotrienes, and are involved in cellular immunoregulation.
      Recent studies have stressed the importance of essential fatty acids in various
      diseases. Patients with atopic dermatitis have altered essential fatty acids
      levels in plasma and a clinical improvement has been shown after oral
      administration of essential fatty acids. The aim of our study was to investigate
      the distribution of essential fatty acids in the membranes of cord blood
      mononuclear leukocytes of newborns at risk of atopy, and to correlate the levels
      of essential fatty acids at birth with total IgE values and with the onset of
      atopic disease. Newborns at risk of atopic disease have a significant reduction
      in arachidonic acid in the membranes of cord blood mononuclear leukocytes. Our
      data show a significant decrease in arachidonic acid in neonates at risk of
      atopy, suggesting that the abnormality of essential fatty acids is a primary
      phenomenon associated with atopic status.

PMID- 7735514
TI  - Variations of airborne summer pollen in southwestern Spain.
AB  - The fact that a considerable proportion of pollen allergy sufferers have an
      upsurge of symptoms in summer prompted us to study the airborne pollen types
      present in the air of Huelva (southwestern Spain) during the months of July,
      August and September. A Cour-type pollen sampler was installed in the center of
      the city. In these months of elevated climatological dryness (high temperatures
      and almost complete absence of rain), 26 different pollen types were detected
      (results from four years of observation: 1989-1992). Quantitatively outstanding
      were Amaranthaceae/Chenopodiaceae, Eucalyptus, Gramineae (Poaceae), Helianthus
      and Ligustrum (comprising 86.06% of the pollen measured). Of these types, only
      extracts of Gramineae and Amaranthaceae are included in the skin tests and
      immunotherapy practiced in the region. Given the allergic potential of the pollen
      of Ligustrum, Helianthus, Eucalyptus and Palmaceae, we performed aerobiological
      evaluations, which may be useful when diagnosing summer pollen allergies.

PMID- 7735515
TI  - Specific hyposensitization in patients allergic to Parietaria officinalis pollen
      allergen.
AB  - The effects of specific hyposensitization in 40 patients with Parietaria
      officinalis-sensitive seasonal rhinoconjunctivitis were studied during three
      years of treatment. The patients were treated with subcutaneous injections of a
      new, partially purified, characterized and standardized pollen extract of P.
      officinalis allergen (alum-absorbed depot preparation). Treatment was applied
      from November to mid March and it was clinically assessed during the plant
      flowering season (mid March to end of June). Laboratory tests were performed
      yearly when beginning and ending treatment. Serum concentrations of P.
      officinalis pollen allergen-specific IgE antibodies decreased (first year: from
      18.7 +/- 7.7 to 17.9 +/- 7.6 PRU/ml; second year: from 16.3 +/- 7.1 to 14.1 +/-
      6.6 PRU/ml; third year: from 12.3 +/- 5.6 to 10.9 +/- 5.6 PRU/ml) and those of
      specific IgG increased (first year: from 15.3 +/- 13.2 to 21.7 +/- 14.0%; second
      year: from 28.5 +/- 13.0 to 36.3 +/- 15.9%; third year: from 29.9 +/- 14.1 to
      38.9 +/- 16.8%) during the treatment. Histamine release from peripheral blood
      leukocytes challenged in vitro with the allergen decreased during the three years
      of the treatment (first year: from 42.3 +/- 13.0 to 33.1 +/- 10.8%; second year:
      from 31.9 +/- 11.9 to 19.1 +/- 8.5%; third year: from 19.4 +/- 4.6 to 14.3 +/-
      4.6%), whereas the size of skin test reaction and the percentage of eosinophils
      among white blood cells remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735516
TI  - Suppression of passive cutaneous anaphylactic reaction by a human serum factor.
AB  - The capacity of human serum to inhibit the IgE-mediated passive cutaneous
      anaphylactic reaction in mouse was established. The active fraction was isolated
      by ammonium sulfate precipitation (33-40% saturation). Its molecular weight, as
      estimated by gel filtration, was found to be 42-66 kd. Affinity chromatography on
      lectins showed affinity of the factor for concanavalin A but not for peanut
      agglutinin. Treatment of the active fraction with exoglycosidases showed that
      mannose in the factor is essential for its biological activity. When the
      inhibitory factor was separated on mouse IgE-coated nitrocellulose membranes, its
      molecular weight estimated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) was 64.5 kd. The factor is thermolabile at 55 degrees
      C. In a population study approximately 28% of human sera showed the presence of
      this factor.

PMID- 7735517
TI  - Assessment of interleukin-2 (IL-2) in sera of healthy and infected newborns.
AB  - Newborns present a certain degree of immunological immaturity, which makes them
      highly susceptible to infection. As interleukin-2 (IL-2) is a cytokine that
      increases the immune response, we performed this study with the object of
      determining whether there are differences in the serum levels of IL-2 in healthy
      newborns and those affected by neonatal sepsis in order to establish if there is
      an increase in the production of IL-2 in systemic neonatal infection. We studied
      three groups of newborns: group 1-20 healthy full-term newborns; group 2-19
      healthy preterm newborns; and group 3-11 infected newborns. The study was
      performed before the seventh day of life. IL-2 levels were determined by
      radioimmunoassay (RIA). Covariant analysis showed no significant differences in
      IL-2 values between the healthy groups (1 + 2) and the infected group (3) (p =
      0.7814).

PMID- 7735518
TI  - Total and specific IgE levels in human hydatid disease determined by enzyme
      immunoassay: serological follow-up after surgery.
AB  - The evolution of both specific and nonspecific IgE in a long-term follow-up after
      surgery in patients with human hydatid disease was studied. Enzyme immunoassays
      using cyanogen bromide-activated cellulose discs as solid phase were employed.
      One hundred and nine postoperative serum samples from 26 patients undergoing
      surgery for hydatid disease were studied. Imaging studies were also carried out
      during the follow-up. In 8 of 26 patients, remaining cysts were detected during
      the follow-up. One year after surgery, total IgE levels decreased to normal
      values in 84.6% of the total number of patients, in 94.5% of the cases in which
      no remaining cysts were detected, and in 62.5% of the patients with remaining
      hydatid cysts. These data highlight the poor value of an isolated postoperative
      IgE determination as a diagnostic marker for remaining hydatidosis. On the
      contrary, 1 year after surgery, the levels of anti-Echinococcus IgE decreased in
      55% of the patients without residual cysts and in 50% of the total number of
      patients. In six patients without remaining hydatid cysts, the levels of specific
      IgE increased 1 year after the surgery. In the group of patients with remaining
      cysts only in three patients did the values of specific IgE decrease, although
      they remained significant. Thus, 1 year after surgery, anti-Echinococcus IgE
      levels were still evident in all patients, although in those without remaining
      cysts there was a predominance of decreasing values.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7735519
TI  - Double-blind, placebo-controlled clinical trial of preseasonal treatment with
      allergenic extracts of Olea europaea pollen administered sublingually.
AB  - In a double-blind, placebo-controlled, pilot clinical trial we evaluated the
      clinical efficacy and safety of immunotherapy (IT) with an extract of the pollen
      of the tree Olea europaea administered sublingually. The parameters tested were
      symptom score, dose-response bioassay of skin prick test and specific IgE and
      IgG, and the absolute value at a single serum dilution of each IgG subclass.
      Fifteen patients allergic to this pollen with symptomatology of rhinitis and/or
      rhinoconjunctivitis were randomly allocated to the placebo group (6 patients) or
      to the extract group (9 patients). Immunotherapy was administered in a short
      preseasonal period of time, practically no side effects being recorded. The group
      of patients treated with extract presented a slightly lower incidence (0.05 < p <
      0.1) of nasal symptoms of sneezing and obstruction, and, more importantly,
      developed less dyspnea (p < 0.05) than the group treated with placebo, suggesting
      that IT can act as prophylaxis for the development of bronchial symptoms. No
      differences were observed in the immunological determinations. Differences in
      skin tests between the two groups displayed a slight significance (0.05 < p <
      0.1) at the end of the trial; hence, a higher concentration of the allergen was
      needed in the group treated with extract to induce the same wheal as in the
      placebo group. In both groups the size of the wheal showed a time-dependent
      variation, which was dependent on the time of the year and independent of the
      type of treatment received, indicating a significant modification in the in vivo
      skin response to allergen challenge, demonstrated by a shift in the kinetics of
      allergen-ligand binding (slope) and in the magnitude of the measured response
      (intercept).

PMID- 7735520
TI  - Delayed hypersensitivity to beta-lactams.
AB  - We present nine patients with delayed allergic reactions to beta-lactams. Four of
      them developed reactions to ampicillin; the diagnostic studies suggested the
      involvement of a type IV hypersensitivity mechanism to an antigenic determinant
      in the side-chain structure, with intradermal and patch tests positive to
      ampicillin but good tolerance to benzylpenicillin. Three patients showed delayed
      hypersensitivity reactions to benzylpenicillin (positive delayed skin tests
      and/or challenges). Arthus-type reactions were seen in two other patients.
      Specific IgE of uncertain relationship to benzylpenicillin and ampicillin was
      later detected in four cases.

PMID- 7735521
TI  - A case of allergy to human insulin associated with high IgG/IgE ratio for
      specific antibodies.
AB  - A 37-year-old woman with a previous history of allergic rhinitis and bronchial
      asthma presented local and generalized allergic reactions to bovine, porcine and
      human insulins. She developed ketoacidosis, high insulin requirements and
      transient hypoglycemic episodes. Several desensitizing schedules were applied in
      order to induce tolerance to human insulin therapy. In addition, the following
      parameters of the humoral immune response were measured in different serum
      samples taken within 13 days after one of the anaphylactic episodes: insulin
      antibodies (binding range = 29.4-47.8%; cutoff = 2.6%), total IgE (range = 500
      850 IU/ml; normal values = 3.7-269 IU/ml), specific IgE (range = 0.42-0.83
      PRU/ml; class 2) and subclasses of specific IgG (IgG1 = 97.2 SDS; IgG2 = 41.1
      SDS; IgG3 = 9.9 SDS; IgG4 = 0.3 SDS, on day 1). A binding capacity of 31.8 IU
      insulin/l obtained by Scatchard analysis was in agreement with episodes of
      elevated insulin requirements and hypoglycemia. A high anti-insulin IgG/IgE
      ratio, along with high levels of specific IgG1 antibodies, suggested that the
      latter antibodies could be involved in the development of anaphylactic episodes.

PMID- 7735522
TI  - Asthma and genetics. Lecture held at Interasma 93 (Jerusalem) during the
      Epidemiology and Genetic Session on October 28, 1993.
AB  - Hypersensitivity to environmental allergens has increased in the last years.
      Several authors have described the physicochemical properties, nucleotide and
      amino acid sequences, and also the three-dimensional structure of unknown
      allergens. The aim is to identify T- and B-cell epitopes and to understand the
      regulatory mechanism of the excessive immune response. The induction of specific
      IgE antibody production in genetically predisposed subjects is the characteristic
      allergens have in common. New molecular biological studies indicate that,
      especially in monosensitized subjects, a correlation exists between the HLA-D
      system and the allergen-specific IgE immune response.

PMID- 7735523
TI  - Mitochondrial DNA diversity in an apomictic Daphnia complex from the Canadian
      high arctic.
AB  - Cyclic parthenogenesis is the ancestral mode of reproduction in the cladoceran
      crustacean, Daphnia pulex, but some populations have made the transition to
      obligate parthenogenesis and this is the only mode of reproduction known to occur
      in arctic populations. Melanism and polyploidy are also common in arctic
      populations of this species. Prior allozyme studies of arctic D. pulex revealed
      substantial levels of clonal diversity on a regional scale. Clonal groupings
      based on cluster analysis of allozyme genotypes do not conform to groupings based
      on the presence/absence of melanin or on ploidy level. In order to further
      elucidate genetic relationships among arctic D. pulex clones, mitochondrial DNA
      (mtDNA) variation was examined in 31 populations from two Canadian high-arctic
      sites. The data were also compared to a previous study of mtDNA variation in
      populations from a Canadian low-arctic site. Cladistic analysis of restriction
      site variation of the entire mitochondrial genome and nucleotide sequence
      variation of the mitochondrial control region was used to construct genetic
      relationships among mitochondrial genotypes. Three distinct mitochondrial
      lineages were detected. One lineage was associated with diploid, nonmelanic
      clones and is the same as the lineage that is found in temperate populations of
      D. pulex. The other two lineages (A & B) were associated with polyploid, melanic
      clones. Sequence divergence between the A and B lineages was 2.4%. Sequence
      divergence between D. pulex and either of these two lineages exceeded
      3%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735524
TI  - Introgression of Luxilus cornutus mtDNA into allopatric populations of Luxilus
      chrysocephalus (Teleostei: Cyprinidae) in Missouri and Arkansas.
AB  - The cyprinid fishes Luxilus cornutus and Luxilus chrysocephalus hybridize
      extensively in a zone extending through the Great Lakes region with extensive
      introgression of L. cornutus mtDNA occurring in populations of L. chrysocephalus
      south of the present hybrid zone in Ohio. Western populations of these two
      species occur adjacent to one another in Missouri but hybridization has never
      been observed. In order to determine if hybridization has occurred historically
      in Missouri, allopatric populations of L. chrysocephalus were analysed for mtDNA
      introgression. Extensive introgression of L. cornutus mtDNA was observed in most
      populations of L. chrysocephalus in Missouri resulting in the elimination of L.
      chrysocephalus mtDNA in many populations. Luxilus cornutus mtDNA in L.
      chrysocephalus is found approximately 300 km south of extant L. cornutus
      populations in Missouri. Luxilus chrysocephalus mtDNA was replaced by four unique
      L. cornutus mtDNA haplotypes, with one particular haplotype becoming fixed in
      several L. chrysocephalus populations. The pattern of introgression suggests that
      historically L. cornutus occupied a more southern distribution in Missouri
      bringing it into contact with western populations of L. chrysocephalus and
      resulting in a hybrid zone.

PMID- 7735525
TI  - Recombinant and wild-type Pseudomonas aureofaciens strains introduced into soil
      microcosms: effect on decomposition of cellulose and straw.
AB  - The effect of a genetically engineered Pseudomonas aureofaciens (Ps3732RNL11)
      strain (GEM) and the parental wild-type (Ps3732RN) on decomposition of cellulose
      paper, straw and calico cloth was assessed after 18 weeks incubation in
      laboratory soil microcosms. Effect(s) of inoculum density (10(3), 10(5), and
      10(8) cells/g dry soil) and single versus multiple bacterial inoculations were
      also investigated. Cellulose paper was completely decomposed after 18 weeks in
      all treatments. There were no significant differences (95% level), between
      treatments, in percentage decomposition of either straw or calico cloth. Recovery
      of the GEM at 18 weeks, using viable plating, was limited to treatments
      originally receiving 10(8) cells/g dry soil. Log 1.8 CFU/g dry soil were
      recovered from the single dose treatment while log 4.2 CFU/g dry soil were
      recovered from the multiple dose treatment. Biolog metabolic tests were used to
      determine if the GEM or parental wild-type had any effect on overall carbon
      utilization in soil. Results suggested they did not. Detection of the recombinant
      lacZY gene sequence in soil using PCR suggested the possibility of viable but
      nonculturable cells and/or persistence of chromosomal DNA.

PMID- 7735526
TI  - Natal dispersal and genetic structure in a population of the European wild rabbit
      (Oryctolagus cuniculus).
AB  - A combination of behavioural observation, DNA fingerprinting, and allozyme
      analysis were used to examine natal dispersal in a wild rabbit population.
      Rabbits lived in territorial, warren based social groups. Over a 6-year period,
      significantly more male than female rabbits moved to a new social group before
      the start of their first breeding season. This pattern of female philopatry and
      male dispersal was reflected in the genetic structure of the population. DNA
      fingerprint band-sharing coefficients were significantly higher for females
      within the same group than for females between groups, while this was not the
      case for males. Wright's inbreeding coefficients were calculated from fingerprint
      band-sharing values and compared to those obtained from allozyme data. There was
      little correlation between the relative magnitudes of the F-statistics calculated
      using the two techniques for comparisons between different social groups. In
      contrast, two alternative methods for calculating FST from DNA fingerprints gave
      reasonably concordant values although those based on band-sharing were
      consistently lower than those calculated by an 'allele' frequency approach. A
      negative FIS value was obtained from allozyme data. Such excess heterozygosity
      within social groups is expected even under random mating given the social
      structure and sex-biased dispersal but it is argued that the possibility of
      behavioural avoidance of inbreeding should not be discounted in this species.
      Estimates of genetic differentiation obtained from allozyme and DNA fingerprint
      data agreed closely with reported estimates for the yellow-bellied marmot, a
      species with a very similar social structure to the European rabbit.

PMID- 7735527
TI  - Nonamplifying alleles at microsatellite loci: a caution for parentage and
      population studies.
AB  - While genotyping wild red deer (Cervus elaphus) at microsatellite loci for
      paternity assignment, we found three loci (MAF65, BOVIRBP and CelJP23) with
      segregating nonamplifying alleles. Nonamplifying alleles were detected through
      mismatches between known mother-offspring pairs and by significant deviations
      from Hardy-Weinberg equilibria. In a wide range of molecular ecology application,
      and especially in parentage assignment, the possible existence of undetectable
      alleles must be taken into account; this may be particularly important for
      microsatellite data.

PMID- 7735528
TI  - Microsatellites reveal high genetic diversity within colonies of Camponotus ants.
AB  - In order to characterize the sociogenetic structure of colonies in the carpenter
      ants Camponotus herculeanus and C. ligniperda, we have developed microsatellite
      markers. The three loci studied were either fixed for different alleles in the
      two species or showed different patterns of polymorphisms. Genotyping of workers
      and males showed that the broods of C. ligniperda include several matrilines, a
      rare phenomenon in the genus. Five alleles from a locus polymorphic in both
      species were sequenced from the respective PCR-products. A part of the length
      variation appeared to be due to changes outside the repeat sequence, and some PCR
      products of an equal length had a different number of dinucleotide repeats.

PMID- 7735529
TI  - DNA fingerprinting provides evidence of discriminate suckling and non-random
      mating in little brown bats Myotis lucifugus.
AB  - Recent advances in DNA extraction and fingerprinting techniques allowed
      examination of genetic similarity of groups of Myotis lucifugus at maternity
      roosts. Mean percentage band-sharing between young was significantly higher than
      between mothers, suggesting fertilization success skewed for individual males or
      male lineages. Mean percentage band-sharing between presumed mothers and young
      was significantly higher than band-sharing between all other groups, suggesting
      that Myotis lucifugus preferentially suckle their own young.

PMID- 7735530
TI  - Transposon signatures: species-specific molecular markers that utilize a class of
      multiple-copy nuclear DNA.
AB  - Transposable elements are mobile sequences found in nuclear genomes and can
      potentially serve as molecular markers in various phylogenetic and population
      genetic investigations. A PCR-based method that utilizes restriction site
      variation of element copies within a genome is developed. These patterns of site
      variation, referred to as transposon signatures, are useful in differentiating
      between closely related groups. Signature data using the magellan
      retrotransposon, for example, is useful in examining relationships within the
      genus Zea and Tripsacum. This method allows transposable elements, or even other
      multiple-copy nuclear DNA sequences, to be generally utilized as molecular
      markers in discriminating between other closely related species and subspecies.

PMID- 7735531
TI  - Multilocus DNA fingerprinting and RAPD reveal similar genetic relationships
      between strains of Oreochromis niloticus (Pisces: Cichlidae).
AB  - Two molecular techniques which reveal highly variable DNA polymorphisms, RAPD and
      multilocus DNA fingerprinting, were used to evaluate genetic diversity between
      six aquacultural strains of Oreochromis niloticus (tilapia) from the Philippines.
      The results using both techniques were in close agreement. Within-strain
      heterozygosity values were similar and were correlated between the two data sets,
      but statistical errors associated with the RAPD data set were lower. Although
      genetic distances between strains were greater using DNA fingerprinting, the
      distances measured using both methods were significantly correlated. Both methods
      were useful in estimating variation between strains, but they offered different
      advantages. RAPD was technically easier to perform and produced results with low
      statistical error, whereas DNA fingerprinting detected greater genetic
      differentiation between strains. The theoretical basis for using RAPD and
      multilocus minisatellite markers for population studies is discussed.

PMID- 7735532
TI  - Applications of 5S rDNA in Atlantic salmon, brown trout, and in Atlantic salmon x
      brown trout hybrid identification.

PMID- 7735534
TI  - Thoracoscopic assisted lobectomy.
AB  - The advances in endoscopic capabilities expanded the potential role of
      laparoscopic and thoracoscopic surgery. The introduction of safe linear stapling
      devices made thoracoscopic assisted segmental lung resections possible. Because
      of the postoperative advantages of a thoracoscopic operation, a technique for
      thoracoscopic lobectomies was developed. Three case reports are presented using
      the same technique. The first two cases report a right lower lobectomy and the
      third case a bilobectomy, right middle and lower lobe.

PMID- 7735533
TI  - Laparoscopic transhiatal esophagectomy with esophagogastroplasty.
AB  - Twelve patients with benign and malignant esophageal diseases were treated by
      transhiatal esophagectomy, without thoracotomy, using abdominal-mediastinal
      dissection conducted by videolaparoscopy. A cervical approach was used to
      retrieve the esophagus and to perform the esophagogastric anastomosis. The
      procedure was indicated in patients with advanced achalasia of the esophagus,
      severe reflux stenosis, squamous cell carcinoma, and adenocarcinoma of the
      esophagus. Three pleural perforations occurred during surgery. Blood loss was
      minimal. One patient required conversion to open surgery, two patients were
      submitted to chest drainage, and three had transitory dysphonia. One patient had
      an anastomotic leak with subsequent stenosis requiring endoscopic dilatation. No
      mortality occurred in this small series.

PMID- 7735535
TI  - Endoscopic removal of retained common bile duct stones in patients with T tube in
      situ.
AB  - Endoscopic sphincterotomy (ES) was performed on 27 patients after cholecystectomy
      with a T tube in situ at a mean interval of 23 days after surgery. A precut
      papillotomy facilitated deep cannulation and subsequent standard ES in three
      patients with impacted ampullary stones. Bile duct clearance was successful at
      the first attempt in 22 of 25 (88%) patients who had common bile duct stones.
      Spontaneous passage of the stones occurred in two patients within 10 days of ES,
      while the T tube was still in situ. In one patient, the T tube had to be removed
      to facilitate spontaneous passage of the stone through the ES opening.
      Choledochoduodenal fistula occurring immediately above the ampulla of Vater was
      found in three (11%) of our patients. Common bile duct exploration is the most
      likely cause of these fistulae. Mild bleeding in one patient was the only
      complication encountered. It is concluded that ES is a relatively safe and
      efficient way of treating common bile duct stones with a T tube in situ.

PMID- 7735536
TI  - Two cases of early gallbladder cancer incidentally discovered by laparoscopic
      cholecystectomy.
AB  - In case 1, a 68-year-old woman with asymptomatic gallstones underwent
      laparoscopic cholecystectomy after radical mastectomy for breast cancer.
      Histological examination revealed gallbladder carcinoma with involvement confined
      to the mucosa and positive margin at the cystic duct. We resected the remnant
      cystic duct with open laparotomy. In case 2, a 63-year-old woman with a diagnosis
      of early rectal cancer underwent laparoscopic cholecystectomy for silent
      gallstones following transanal resection of the rectal tumor. Pathologic analysis
      illustrated a gallbladder carcinoma with wide mucosal spread and minimal invasion
      into the subserosal layer. No additional treatment was warranted. As laparoscopic
      cholecystectomy has become widely used, an increase in the number of resected
      cases of early gallbladder cancer can be expected, especially among asymptomatic
      gallstone patients. Additional treatment should be determined through meticulous
      microscopic investigation of the specimen, with special attention to the depth of
      invasion and the range of mucosal spread.

PMID- 7735537
TI  - Laparoscopic diagnosis and treatment of Morgagni hernia.
AB  - The application of new minimally invasive techniques in the diagnosis and
      treatment of surgically correctable diseases continues to produce impressive
      results. Herniae of the Foramen of Morgagni are unusual abdominal wall defects
      which have historically been difficult to diagnose. Interestingly, laparoscopy
      was utilized for the diagnosis and repair of three such herniae during a 5-month
      period. All of these repairs were performed by one primary author in conjunction
      with co-authors. In this report we will review this rare hernia and report our
      technique of repair. We believe that an aggressive approach to diagnostic
      laparoscopy may produce cost-effective solutions to old and new intraabdominal
      problems.

PMID- 7735538
TI  - Laparoscopic paraesophageal hernia repair with mesh.
AB  - A type II paraesophageal hernia is usually an asymptomatic condition found
      incidentally in an elderly patient. It is a potentially devastating problem
      because it can present as severe blood-loss anemia or acute, life-threatening
      gastric volvulus. The medical and surgical literature is replete with
      recommendations for surgical repair, but underlying medical illnesses have led to
      delays in the use of this treatment of choice. Five extreme elderly patients
      safely underwent the standard "Boerema" repair with gastropexy under laparoscopic
      guidance. With the advent of laparoscopy, a safe, minimally invasive approach is
      available to the high-risk patient group.

PMID- 7735539
TI  - Two laparoscopic techniques for resection of leiomyoma in the stomach.
AB  - We report two surgical treatments by laparoscopic techniques of a leiomyoma in
      the stomach, each for one patient. The patients, one a 59-year-old man and the
      other a 28-year-old woman, were found to have an asymptomatic submucosal tumor in
      the stomach in an annual medical screening. One tumor, 1.5 cm in maximum
      diameter, was located on the anterior wall of the gastric body and was excised
      extracorporeally by laparoscopy-guided surgery. The other was 1.9 cm in maximum
      diameter, on the anterior wall of the antrum, and was excised intracorporeally
      using only laparoscopic surgery. Their postoperative courses were uneventful.
      They drank clear liquid after the removal of a nasogastric tube on the first
      postoperative day and had a solid meal on the second postoperative day. They were
      discharged from the hospital on the seventh and eighth postoperative days.

PMID- 7735540
TI  - Laparoscopic cholecystectomy: a continuing plea for routine cholangiography.
AB  - The purpose of this clinical study was to demonstrate the usefulness of routine
      intraoperative cholangiography (IOC) and the safety of laparoscopic
      cholecystectomies (LC) in a community hospital. There were no ductal injuries and
      perioperative complications were extremely low. Patients (n = 236) with
      symptomatic gallstone disease, acalculus cholecystitis, or gallbladder polyps
      underwent LC from March 1991 to June 1993. During this period two patients were
      not considered appropriate candidates for this procedure. There were 172 women
      and 64 men ranging in age from 15 to 84 years. Four had preoperative endoscopic
      retrograde cholangiopancreatographies (ERCPs) for suspected choledocholithiasis.
      Elective LC was performed on 194 patients and emergency LC on 42 patients. The
      average operating time for elective LCs was 89 min and 97 min for emergency LCs.
      Thirty-six percent of patients had previous abdominal or pelvic surgery. IOC was
      attempted in 99% of patients and successful in 89%. Five percent had
      choledocholithiasis. Laparoscopic duct exploration was performed on four
      patients. Six patients had postoperative ERCP with stone extraction. Three
      percent of elective patients had additional surgery. One patient had LC during
      pregnancy (17 weeks), with a normal recovery and successful outcome of the
      pregnancy. Six elective and four emergency patients were converted to open
      cholecystectomy, a conversion rate of 4%. There were no ductal or vascular
      injuries, intraoperative haemorrhages or deaths. There were one small bowel
      laceration (0.4%). Postoperative complications included seven wound infections
      (3%), four bile leaks (2%), three trocar site haemorrhages (1%), one
      intraabdominal haemorrhage (0.4%), one suspected halothane hepatitis (0.4%), one
      drug-induced cholestatic jaundice (0.4%), and one subcutaneous emphysema
      (0.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735541
TI  - Introduction of a new double-looped suture.
AB  - Two new sutures are introduced for laparoscopic two-handed instrument suturing
      and knot tying, as well as a device for making them. In the first design, a
      nonslipping loop is placed at each end of a straight suture; they act as
      anchoring devices to maintain the suture in the two-dimensional plane of focus of
      the laparoscopic camera. The loops provide a large surface area that facilitates
      grasping the suture during the rotational and pulling maneuvers employed in
      instrument knot tying. The double-looped suture can be used for tying off and
      retracting tubular structures. The second design consists of a suture ligature
      with a curved or straight needle at one end and a single, non-slipping loop at
      the other. Illustrations demonstrate tying and suturing techniques for
      approximating tissue with the new sutures. A device consisting of two pairs of
      posts, for making the looped suture in a uniform fashion, is also discussed.

PMID- 7735542
TI  - Video-assisted right lower lobectomy for a lung cancer with mini-thoracotomy.
AB  - We report a case of T1N0M0 lung cancer in which we successfully performed video
      assisted right lower lobectomy and mediastinal lymph node dissection. The
      lobectomy was done on a 64-year-old woman who had a 2-cm adenocarcinoma in the
      right lower lobe. The procedure could be done safely and adequately using three
      trocars and a 5-cm mini-thoracotomy. The patient had an uncomplicated
      postoperative course and was satisfied with minimal postoperative pain, quick
      recovery, and minute skin scars. Video-assisted lobectomy may be a reasonable
      approach in selected patients of primary lung carcinoma.

PMID- 7735543
TI  - Subcutaneous periumbilical metastasis of a gallbladder carcinoma after
      laparoscopic cholecystectomy.
AB  - The frequency of gallbladder carcinoma is 1.2 to 7.4% of all cholecystectomy
      specimens. In open cholecystectomy for gallstone disease, undetected gallbladder
      carcinoma is found postoperatively in the histological examination in 0.3%. Tumor
      cells of these clinically inapparent gallbladder carcinomas can be implanted at
      the trocar sites during laparoscopic cholecystectomies. We report a case with
      subcutaneous tumor seeding at the navel trocar insertion site in a 65-year-old
      woman.

PMID- 7735544
TI  - A robotic camera for laparoscopic surgery: conception and experimental results.
AB  - The aim of this project was to replace the surgical assistant for common
      laparoscopic procedures with a robotic camera. The motions of the human camera
      operator were defined and expressed mathematically by a spherical displacement
      model. A revolving robotic arm with six degrees of freedom was employed in
      conjunction with this model as an automated camera in the performance of
      cholecystectomy, Taylor and Nissen procedures in animals, and cholecystectomy in
      humans. It represents a first step toward the introduction of robotic technology
      in laparoscopic surgery.

PMID- 7735545
TI  - Laparoscopic highly selective vagotomy incorporating a retrogastric approach.
AB  - We performed posterior and anterior highly selective vagotomy in six duodenal
      ulcer patients, using a retrogastric approach to the posterior gastric branches
      of the vagus nerve. The details of the procedure and the results obtained are
      described.

PMID- 7735546
TI  - Laparoscopic cholecystectomy and endoscopic sphincterotomy under a single
      anesthetic: a case report.
AB  - Several options have been described for the management of unsuspected common bile
      duct stones diagnosed for the first time by transcystic cholangiography during
      laparoscopic surgery. These include immediate conversion to open laparotomy and
      formal common bile duct exploration, laparoscopic bile duct exploration, or
      postoperative biliary endoscopy (i.e., ERCP with sphincterotomy and stone
      extraction). Herein we describe a fourth option which allows the surgeon to
      manage both cholelithiasis and choledocholithiasis at the time of laparoscopic
      intervention: endoscopic sphincterotomy performed immediately after laparoscopic
      cholecystectomy under one anesthetic. This option seems the most logical when the
      surgeon wishes to preserve the minimally invasive approach.

PMID- 7735547
TI  - Laparoscopic management of volvulated Meckel's diverticulum.
AB  - Laparoscopy in the emergency setting is a logical extension of this technique.
      Open laparoscopy is particularly useful in the management of the acute abdomen.
      In our institution, after a sequential work-out that includes physical
      examination, laboratory data, plain abdominal roentgenograms and ultrasonography,
      diagnostic laparoscopy is advocated. We present the laparoscopic treatment of an
      intestinal obstruction caused by a volvulus around Meckel's diverticulum. The
      efficacy and safety of the diagnostic and/or therapeutic laparoscopic procedures
      in the emergency setting are discussed.

PMID- 7735548
TI  - Is laparoscopic colectomy a safe procedure in synchronous colorectal carcinoma?
      Report of a case.
AB  - This clinical report describes a patient with sigmoid cancer who underwent a
      laparoscopic-assisted sigmoidectomy while also having an unsuspected carcinoma of
      cecum. We discuss the necessity of a complete preoperative evaluation (total
      colonoscopy and barium enema) in patients with colon cancers amenable to
      treatment by laparoscopic approach.

PMID- 7735549
TI  - Laparoscopic removal of a large laparotomy pad forgotten in situ.
AB  - Objects forgotten during surgery are still an important complication with ethical
      and forensic implications. This case report describes a splenectomized patient
      with type II Hodgkin's disease. A large laparotomy pad (68 x 48 cm) forgotten in
      situ during a staging operation 6 months previously was removed laparoscopically.
      In asplenic patients with a permanent immune deficiency it is especially
      advantageous to perform surgery via the "closed" route whenever possible.

PMID- 7735550
TI  - Early gallbladder cancer discovered at the time of laparoscopic cholecystectomy.

PMID- 7735551
TI  - Routine application of polymerase chain reaction in the diagnosis of
      monoclonality of B-cell lymphoid proliferations.
AB  - We evaluated four polymerase chain reaction (PCR) methods for their efficiency in
      detecting monoclonality in a well-characterized panel of frozen and paraffin
      embedded B-cell lymphoid proliferations. These approaches (referred to as FR3,
      FR3A, FR2, and FR1) are based on amplification of rearranged immunoglobulin heavy
      chain genes, using primers recognizing framework regions I, II, or III. FR3, FR3A
      and FR2 approaches reproducibly detected monoclonality in 51%, 72%, and 67% of
      DNAs from frozen lymphomas, respectively. No false-positives were observed. The
      combination of FR2 and FR3A methods raised the figure to 85%. Comparable results
      were obtained using paraffin-embedded lymphomas. Reproducibility of FR1 approach
      was unsatisfactory. The efficiency of all PCR approaches varied depending on
      lymphoma type. The highest detection rate was in small/intermediate cell and the
      lowest in centro-follicular lymphomas. Limiting dilution assays showed that PCR
      methods were able to detect monoclonal B-cell DNA representing 5% of nonlymphoid
      and 20% of polyclonal B-cell DNA. A diagnostic protocol may include quick and
      cost-effective PCR screening, particularly in cases of undetermined small cell
      lymphoid proliferations observed in fine needle aspirates or endoscopic biopsies.
      This would also reduce call-up of patients to obtain unfixed biopsies.

PMID- 7735552
TI  - Polymerase chain reaction detection of immunoglobulin gene rearrangement and bcl
      2 translocation in archival glass slides of cytologic material.
AB  - Cytologic evaluation of lymph node fine-needle aspirates and serous effusions is
      a rapid and useful means for establishing the diagnosis of a variety of
      lymphoproliferative disorders. However, in some instances, cytologic findings are
      not sufficient to establish a diagnosis of lymphoma, thus necessitating the use
      of ancillary procedures, the most frequent of which is immunophenotyping. In this
      respect, the usefulness of molecular markers, such as clonal immunoglobulin gene
      rearrangements or chromosomal translocations, have been less well evaluated.
      Follicular lymphoma constitutes an interesting disease for such a study because
      these tumors possess characteristic histopathologic features and contain two
      potential molecular markers, that is, a clonal immunoglobulin gene rearrangement
      and a bcl-2 gene translocation [t(14;18)]. In the present study, we evaluated,
      retrospectively, the cytologic material from four lymph node fine-needle
      aspirates and one pleural effusion of five patients with biopsy-proven follicular
      lymphoma. In four of the cases, definitive diagnosis of lymphoma had not been
      possible solely from cytologic evaluation. DNA was isolated from archival air
      dried samples present on glass slides and amplified by the polymerase chain
      reaction (PCR) for detection of either a clonal immunoglobulin heavy chain gene
      rearrangement or bcl-2 translocation (major breakpoint region). An immunoglobulin
      heavy chain gene rearrangement was detected in four of five patients, and two
      patients had the bcl-2 translocation by PCR. The effusion case was identical by
      gel electrophoresis with product amplified from a lymph node biopsy of the same
      patient and DNA extracted directly from fresh pleural effusion cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7735553
TI  - Monoclonality in gastric lymphoma detected in formalin-fixed, paraffin-embedded
      endoscopic biopsy specimens using immunohistochemistry, in situ hybridization,
      and polymerase chain reaction.
AB  - Diagnosis of gastric malignant lymphoma remains a challenge, especially when the
      tissue source is endoscopic biopsy specimens. Once an atypical lymphoid
      infiltrate is found, demonstration of clonality is the key to establishing a
      diagnosis of the disease. For this purpose, we evaluated the usefulness of
      immunohistochemistry, in situ hybridization, and polymerase chain reaction (PCR)
      using formalin-fixed, paraffin-embedded endoscopic materials from 20 patients
      with B-cell malignant lymphomas. Template DNA for PCR was obtained by
      microdissecting Giemsa-stained sections using a serial hematoxylin and eosin
      section as a guide. Clonal rearrangement bands were demonstrated in 15 of 20
      cases (75%) by PCR, whereas expression of monotypic light-chain mRNA was detected
      in seven of 20 (35%) by in situ hybridization and monotypic light-chain
      restriction in four of 20 (20%) by conventional immunohistochemistry. Although
      less sensitive than PCR, in situ hybridization was useful for localizing the
      expression of target mRNAs with cellular accuracy and with low background
      staining. In addition, two cases were found to be monoclonal only by in situ
      hybridization, and not by PCR. The results showed that clonal proliferation is
      detected with the greatest sensitivity with PCR using small routinely processed
      biopsy specimens and that a difficulty with the PCR method in terms of cellular
      localization was partially overcome using a microdissection procedure that
      provided at least tissue-level accuracy.

PMID- 7735554
TI  - Disseminated, multiclonal Epstein-Barr virus-associated lymphoproliferative
      disease in a patient with hematological and immunological anomalies. Molecular
      analysis correlates with morphological appearance.
AB  - We report a case of a 21-year-old woman with hematopoietic, immunological, and
      congenital dysmorphic abnormalities, who died following rapidly progressive,
      disseminated Epstein-Barr virus (EBV)-associated lymphoproliferative disease
      (LPD). Polymerase chain reaction (PCR) amplification of formalin-fixed paraffin
      embedded tissue showed differences in the clonality of each separate
      lymphoproliferative lesion examined, as determined by immunoglobulin heavy chain
      (IgH) gene rearrangement. PCR analysis also demonstrated that all lesions
      contained EBV genome. Since DNA had been extracted from paraffin blocks, a direct
      comparison of morphology and clonality could be made in each individual lesion.
      The evidence from this study indicates that the monoclonal tumors arose de novo
      in multiple sites and that the polyclonal background observed in some lesions
      reflected a substantial concomitant inflammatory response.

PMID- 7735555
TI  - Polymerase chain reaction detection of the t(11;14) translocation involving the
      bcl-1 major translocation cluster in mantle cell lymphoma.
AB  - The utility of polymerase-mediated assays in the detection of the t(11;14)
      involving the bcl-1 major translocation cluster (bcl-1 MTC) was evaluated by
      analyzing DNA from 33 patients with mantle cell lymphoma, 14 patients with other
      non-Hodgkin's lymphomas, and five patients with reactive lymphoid hyperplasia.
      The polymerase chain reaction (PCR) assay was performed using a consensus
      immunoglobin heavy-chain joining region primer in conjunction with a chromosome
      11 specific oligonucleotide primer flanking the translocation site. The
      sensitivity and specificity of the assay were confirmed by correlation of the
      (PCR) assay data with restriction analysis. Rearrangements at the bcl-1 MTC were
      detected in 13 (39%) of 33 cases of mantle cell lymphoma by PCR and in 13 (48%)
      of 27 cases by restriction analysis. Amplicons were detectable by PCR in 85% (11
      of 13) of the cases shown to be bcl-1 rearranged by restriction analysis. Failure
      to detect amplification products in DNA samples from non-mantle cell lymphomas
      and reactive follicular hyperplasia further confirmed the specificity of the
      assay. Sequential hybridization of the PCR products with oligonucleotide probes
      3' to the bcl-1 MTC primer revealed that the breakpoints in the bcl-1 MTC were
      clustered around an Sst I restriction site over a range of 170 base pairs. The
      study demonstrates that PCR-mediated assay for the detection of the t(11;14) at
      the bcl-1 MTC is specific and sensitive and can be used as an adjunct to
      restriction analysis in routine diagnostics.

PMID- 7735556
TI  - Primary renal carcinoid tumor with molecular abnormality characteristic of
      conventional renal cell neoplasms.
AB  - Carcinoid tumor of the kidney is a rare neoplasm of uncertain histogenesis.
      Attempts to elucidate its cell of origin have been made, but there is a lack of
      experimental proof. We present a case of primary renal carcinoid tumor with a
      characteristic molecular abnormality and discuss its histogenetic implications.
      Histologic, immunohistochemical, and electron microscopic analyses revealed
      features typical of carcinoid tumor, and DNA flow cytometric analysis showed
      diploid pattern. Molecular genetic studies of informative WT1, p53, and 3p21 loci
      revealed loss of heterozygosity only at the D3F15S2 locus (3p21 telomeric). The
      similarity between the molecular abnormality in the present case and that in most
      renal cell carcinomas suggests a possible common genetic event in the genesis of
      these neoplasms.

PMID- 7735557
TI  - A new polymorphic site in intron 2 of TP53 characterizes LOH in human tumors by
      PCR-SSCP.
AB  - Many human cancers present deletions of the short arm of chromosome 17, which
      includes the TP53 locus. We detected a new polymorphism in intron 2 of the TP53
      gene using PCR-SSCP and used this polymorphic site as a marker to detect loss of
      heterozygosity in 135 human tumors (73 soft tissue sarcomas, and 48 colorectal
      and 14 bladder carcinomas). Heterozygosity for this site was 41.5% in this study
      group and tumor-specific loss of alleles occurred in 43% of informative cases.
      Allelic losses were more frequently detected at this site than at that in which
      restriction fragment length polymorphism (RFLP) is located, as detected by the
      pHp53B probe. It is concluded that this novel approach has several advantages,
      including detection of a high incidence of informative cases and minimal tissue
      requirements.

PMID- 7735558
TI  - Correlation of p-glycoprotein detection by immunohistochemistry with mdr-1 mRNA
      levels in osteosarcomas. Pilot study.
AB  - All the factors that influence prognosis in patients with osteosarcomas have not
      been fully determined. One reported predictor of poor outcome is increased multi
      drug resistant gene (mdr-1) expression, as measured by reverse transcription and
      polymerase chain reaction (RT-PCR). We examined whether immunostaining for p
      glycoprotein, the protein product of mdr-1, could be used instead of RT-PCR to
      indicate the presence of the multidrug-resistant phenotype. The sensitivity of
      the immunostaining was determined using KB cell sublines. For 13 cases of
      osteosarcoma, samples were immunostained for p-glycoprotein and the levels of mdr
      1 expression quantitated with use of RT-PCR. Three osteosarcomas with
      undetectable levels of mdr-1 expression by RT-PCR were negative
      immunohistochemically. Ten cases showed mdr-1 expression ranging from
      approximately 1 to 32 copies of mdr-1 mRNA/cell. Of these cases, five cases
      contained occasional tumour cells with positive immunostaining. There was no
      correlation between levels of expression and the presence or number of
      immunoreactive cells. These results indicate that the presence of p-glycoprotein
      immunostaining does not reliably correlate with the level of mdr-1 expression.
      However it may be useful in conjunction with RT-PCR to further define different
      subgroups of osteosarcomas that may have different prognoses, and this is
      currently under investigation.

PMID- 7735559
TI  - Genetic alterations of microsatellites on chromosome 18 in human breast
      carcinoma.
AB  - Allelic alterations of chromosome 18 microsatellites were determined using normal
      and tumor DNA pairs from 29 patients with infiltrating ductal carcinoma of the
      breast. Loss of heterozygosity was detected in 62% (18 of 29 patients) of the
      tumors at one or more of these microsatellites. Eight of the 18 patients
      exhibited deletions in the region at 18q21.1. This chromosomal band is known to
      contain a tumor suppressor gene (DCC) whose expression is frequently inactivated
      in several types of cancer. Ten other patients had deletions in regions not
      included in the DCC locus. Five of these patients revealed a common deletion at
      the D18S50 locus (18q23), and the other five patients had deletions in various
      other regions of the chromosome. No apparent correlation between loss of
      heterozygosity of chromosome 18 microsatellites and the clinical stage was found
      in this series. The results indicate that, in addition to the DCC locus, the
      18q23 region is likely to contain a second tumor suppressor gene relevant to
      breast carcinogenesis. Four percent of all microsatellites tested in these
      patients showed allelic differences in the sizes of repeat units between tumor
      and the corresponding constitutional DNAs. The pattern of allele instability
      observed in breast carcinoma differed from that originally reported in a
      hereditary type of colorectal carcinoma. The observation suggests that this
      phenomenon is not a mechanism specific to neoplastic processes in breast
      carcinoma.

PMID- 7735560
TI  - Identification of the same HRAS1 mutation in a primary minimally invasive
      follicular carcinoma of the thyroid gland and its bone metastasis developed 15
      years later.

PMID- 7735561
TI  - Polymerase chain reaction versus Southern blot hybridization. Detection of
      immunoglobulin heavy-chain gene rearrangements.
AB  - To determine efficiently the clonality of B-cell lymphoproliferative disorders,
      we modified an immunoglobulin heavy-chain (IGH) gene rearrangement polymerase
      chain reaction (PCR) assay that requires only a single primer germline variable
      (VH) and joining (JH) pair and does not involve nested priming, blot
      hybridization, radioactivity, or sequencing of the amplified PCR product. This
      simple PCR technique enabled detection of IGH gene rearrangements in as little as
      10 pg (one cell equivalent) of DNA or when the clonal-to-polyclonal B-cell ratio
      was experimentally set at 1:1000. We detected IGH gene rearrangements in 83.5%
      (71 of 85) of clonal B-cell processes, a sensitivity approaching that of more
      cumbersome multiple primer and nested primer assays. Moreover, this technique is
      equally effective with fixed tissues, either B5 or formalin, and can be performed
      on minute samples, histologic sections, fine-needle aspirates, or cerebrospinal
      fluids. When compared with conventional Southern blot analysis using a genomic JH
      probe, the PCR assay demonstrated IGH gene rearrangements in 82% (37 of 45) of B
      cell processes positive by Southern blot. No false-positive results were observed
      in 29 negative control tissues. We now use IGH gene PCR routinely in our
      laboratory for the detection of clonal B-cells in virtually any tissue sample as
      an aid in early diagnosis, staging, and monitoring, and the Southern blot
      procedure is reserved for only a minority of diagnostic cases. for only a
      minority of diagnostic cases.

PMID- 7735562
TI  - Transient alterations in cellular permeability in cultured human proximal tubule
      cells: implications for transport studies.
AB  - Primary cultures of human proximal tubule (HPT) cells possess the characteristics
      of a tight epithelium and retain the characteristics of in vivo renal function.
      HPT cells form confluent monolayers when grown on collagen-coated polycarbonate
      inserts in a hormonally defined serum-free medium. However, initial studies of
      transepithelial transport observed large bidirectional fluxes of the paracellular
      probe inulin. The present studies were designed to assess the transformation of
      HPT cell tight junctions to a "leaky" state and subsequent recovery. The apparent
      transepithelial electrical resistance of HPT cells at confluence was 952.0 +/-
      70.0 ohms*cm2, suggesting a well-developed tight junction-mediated paracellular
      pathway in this epithelium. However, replacement of the growth media produced an
      immediate 90% drop in the initial resistance, which was paralleled by an
      increased flux of inulin and of phenol red. This transient abolition of barrier
      function spontaneously reestablished over 1-2 h by a process that was dependent
      on the ionic composition of the added media. Complete recovery of cellular
      resistance was paralleled by markedly decreased fluxes of inulin and of phenol
      red. The recovery of cellular barrier function was inhibited by cytochalasin B
      suggesting an intracellular action, not a physical disruption of the monolayer.
      These results suggest that the tight junctions in these cells appear to
      transiently produce a leaky state during removal of the media, but rearrange to a
      "tight conformation" when incubated in the appropriate media.

PMID- 7735563
TI  - Isoenzyme analysis as a rapid method for the examination of the species identity
      of cell cultures.
AB  - One of the major problems in cell culturing is the misidentification or cross
      contamination of authentic continuous cell lines. We applied a rapid and
      efficient isoelectric focusing (IEF) technique for the routine analysis to detect
      interspecies contamination of cell cultures and for the identification of unknown
      animal cell lines. The method is based on the isoelectric separation of a
      specific set of intracellular enzymes which can be used to distinguish between
      cell lines of human, murine, or other mammalian origin. By means of preformed
      agarose gels, standardized conditions and equipment, this technique is especially
      applicable for routine work and allows the analysis of a large number of unknown
      samples with reproducible results. One hundred seventy-seven cell lines which
      have been sent to the Department of Human and Animal Cell Cultures at the DSM
      (Deutsche Sammlung von Mikroorganismen and Zellkulturen) were analyzed for
      species authentication; only three cell lines were found not to be of the
      presumed species. Our study strongly emphasizes standardized IEF as an efficient
      and rapid method for routinely monitoring the authenticity of cell lines.

PMID- 7735564
TI  - The matrix form of collagen and basal microporosity influence basal lamina
      deposition and laminin synthesis/secretion by stratified human keratinocytes in
      vitro.
AB  - The ability of the collagen matrix form to support the formation of a basal
      lamina by cultured normal human epidermal keratinocytes (NHEK) was determined
      using transmission electron microscopy. The collagen matrix forms tested in this
      study were a) a dry type I collagen film and b) a type I collagen gel. NHEK were
      grown for 14 days on the following five different substrates: plain plastic
      culture dishes without the addition of collagen (PP); plain plastic culture
      dishes overlaid with a dry, aldehyde-crosslinked type I collagen film (DCF-P);
      plain plastic culture dishes overlaid with an aldehyde-crosslinked type I
      collagen gel (GEL-P); Millipore Millicell CM microporous membranes overlaid with
      a dry, aldehyde-crosslinked type I collagen film (DCF-CM); and Millipore
      Millicell CM microporous membranes overlaid with an aldehyde-crosslinked type I
      collagen gel (GEL-CM). NHEK maintained for 2 wk on PP and DCF-P were unable to
      secrete a basal lamina. NHEK grown for 2 wk on the GEL-P and GEL-CM substrates,
      however, secreted a contiguous basal lamina at the GEL-NHEK interface. To
      determine if the appearance of this basal lamina correlated with laminin
      synthesis, laminin was immunoprecipitated from cellular extracts, as well as
      media from the apical and basal chambers. NHEK grown on the GEL-P substrate
      synthesized more laminin than did NHEK grown on the other four alternative
      substrates. In addition, NHEK grown on GEL-CM were able to direct more laminin to
      the basal compartment than NHEK grown on DCF-CM substrates.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7735565
TI  - Characterization and co-culture of novel nontransformed cell lines derived from
      rat endometrial epithelium and stroma.
AB  - Normal and neoplastic growth of epithelial cells depends on mutual interactions
      between epithelial and stromal cells. As a tool for the study of the underlying
      molecular mechanisms, we have developed temperature-sensitive, nontransformed
      cell lines derived from rat uterine epithelium and stroma by transfecting primary
      cultures with a temperature-sensitive mutant of the SV40 large T antigen. The
      epithelial and stromal cell lines obtained shared relevant morphological
      characteristics with the primary cells from which they were derived.
      Immunocytochemical analysis showed that the epithelial cell lines expressed the
      intermediate filament cytokeratin, whereas the stromal lines expressed the
      intermediate filament vimentin. Alkaline phosphatase activity was present in all
      cell lines examined. All cell lines were anchorage dependent and did not form
      foci. One epithelial cell line expressed oxytocin mRNA, a gene product recently
      shown to be highly expressed in vivo in the uterine epithelium at term. If grown
      on Matrigel, this cell line formed domelike structures, a further characteristic
      of its differentiated phenotype. In an attempt to reconstitute an endometrium in
      vitro, epithelial cells were seeded on top of a layer of stromal cells. Paraffin
      cross sections showed that this in vitro system consisted of a bilayer structure.
      Four to five cuboidal epithelial cells were typically anchored atop one stromal
      cell, forming an endometriumlike tissue. The present in vitro system should
      provide a useful model for further studies on endometrial functions and
      epithelial/stromal cell interactions at a molecular level.

PMID- 7735566
TI  - Complement-dependent induction of DNA synthesis and cell proliferation in human
      liver connective tissue cells in vitro.
AB  - Liver connective tissue cells (LCTC) isolated from patients with fibrotic livers
      have morphological and biochemical characteristics of myofibroblasts. We have
      examined the proliferation of LCTC derived from normal livers and from livers
      with fibrosis of different etiologies, as well as proliferation of skin
      fibroblasts. We have compared proliferation rates in the presence of fresh human
      serum and heat-inactivated serum. While skin fibroblast and LCTC from normal
      liver showed no difference, proliferation of LCTC from fibrotic livers was
      markedly decreased in the presence of heat-inactivated serum. We demonstrate that
      the native complement component C1 is a factor involved in the induction of DNA
      synthesis and proliferation of LCTC isolated from fibrotic livers. We propose
      that native C1, acting probably in cooperation with other growth factors, is
      involved in the expansion of connective tissue cells during the development of
      liver fibrosis.

PMID- 7735567
TI  - An efficient method for routine Epstein-Barr virus immortalization of human B
      lymphocytes.
AB  - A variety of methods exist for the immortalization of B lymphocytes by Epstein
      Barr virus due to the simplicity of such techniques to establish cell lines with
      stable genomic DNA. Two different methods for immortalizing lymphoblastoid cell
      lines were compared for differences in techniques and materials, time between
      initiation and immortalization, and success rate of immortalization. An
      incubation period in Epstein-Barr virus and the use of conditioned media improved
      immortalization efficiency from 86 to 98% and decreased the time (usually weeks)
      from culture initiation to cryopreservation. The resulting cell bank was used to
      produce DNA for genetic studies focusing on the genes involved in non-insulin
      dependent diabetes mellitus.

PMID- 7735568
TI  - Isolation and culture of intralobular ducts from the hamster pancreas.

PMID- 7735569
TI  - A fluorescence based cell adhesion assay using Terasaki plates.

PMID- 7735570
TI  - Effect of fibroblast growth factor-1 on the three-dimensional growth and
      morphogenesis of human salivary gland epithelial cells embedded in collagen gels.

PMID- 7735571
TI  - Molecular structure-dependent cytotoxic effect of ascorbate derivatives.

PMID- 7735572
TI  - A new insect cell line from the Colorado potato beetle.

PMID- 7735573
TI  - LLC-PK1 epithelia as a model for in vitro assessment of proximal tubular
      nephrotoxicity.
AB  - LLC-PK1 cells, an established epithelial cell line derived from pig kidney, were
      used as a model system for assessment of nephrotoxic side effects of three
      cephalosporin antibiotics: cephaloridine, ceftazidime, and cefotaxime. Toxic
      effects of these xenobiotics were monitored on confluent monolayers by light and
      electron microscopy and by the release of cellular marker enzyme activities into
      the culture medium. In addition, LLC-PK1 cells were grown on microporous
      supports, and cephalosporin-induced alteration of epithelial functional integrity
      was monitored by a novel electrophysiologic approach. For this purpose, an Ussing
      chamberlike experimental setup was used. The dose-dependent effects on
      transepithelial ionic permselectivity were monitored under conditions in which
      defined fractions of the apical culture medium NaCl contents were replaced iso
      osmotically by mannitol. This method of determining the functional intactness of
      the epithelial barrier by measuring dilution potentials was found to be far more
      sensitive than monitoring cell injury by means of morphology or measurement of
      enzyme release. As expected from animal experimental data, a dose-dependent
      disruption of monolayer integrity was detected with all three methodologies
      applied. Cephaloridine was found the most toxic compound followed by ceftazidime,
      where a 3-fold, and cefotaxime, where a 10-fold dose of that of cephaloridine was
      needed to produce cell injury. Measurement of transepithelial dilution potentials
      was more sensitive as compared to the release of the apical plasma membrane
      marker enzyme activities alkaline phosphatase and gamma-glutamyltranspeptidase,
      the cytosolic lactate dehydrogenase, or the mitochondrial glutamate
      dehydrogenase. The data were compared to the effects of the aminoglycoside
      antibiotic gentamicin, which at least with respect to its effects on LLC-PK1
      morphology and enzyme release, but not transepithelial electrical properties, was
      already investigated.

PMID- 7735574
TI  - Should non-small cell carcinoma of the lung be treated with chemotherapy? Pro:
      chemotherapy is for non-small cell lung cancer.

PMID- 7735575
TI  - Should non-small cell carcinoma of the lung be treated with chemotherapy? Con:
      therapeutic empiricism--the case against chemotherapy in non-small cell lung
      cancer.

PMID- 7735576
TI  - The origins of obstructive airways disease. A role for diet?

PMID- 7735577
TI  - Prioritizing asthma research: the need to investigate childhood asthma.

PMID- 7735578
TI  - The assessment and management of adults with status asthmaticus.
AB  - Despite advancing knowledge of the pathophysiology and treatment of asthma,
      asthma morbidity and mortality are on the rise. To help avert this trend,
      clinicians and patients must focus their attention on the early identification
      and treatment of asthma exacerbations. As in the words of Dr. Thomas Petty: " ...
      the best treatment of status asthmaticus is to treat it three days before it
      occurs." (7) Still, there will be asthmatics with life-threatening attacks that
      require careful assessment and aggressive management. Inhaled beta-agonists,
      systemic corticosteroids, and oxygen remain the drugs of choice in SA.
      Anticholinergics play a lesser role in the treatment of acute asthma, and debate
      continues regarding the efficacy of theophylline in this setting. Available data
      do not support the routine use of magnesium sulfate or antibiotics in patients
      with SA. Patients failing drug therapy should be considered early for intubation
      and mechanical ventilation. A strategy of mechanical ventilation that prolongs TE
      by limiting VE and decreasing inspiratory time, and that tolerates hypercapnia,
      avoids excessive lung hyperinflation and barotrauma and should improve the
      outcome of these most critically ill asthmatics. Intubated and mechanically
      ventilated patients should be aggressively sedated. Paralytic agents should be
      used only if adequate control of the cardiopulmonary status cannot be achieved by
      sedation alone. Minimizing the use of paralytic agents may decrease risk of
      myopathy and other adverse consequences of muscle paralysis. Finally, after
      successful treatment of a life-threatening episode of asthma, the treatment team
      should address prevention of future episodes of SA prior to discharge.

PMID- 7735579
TI  - How detrimental is chronic use of bronchodilators in asthma and chronic
      obstructive pulmonary disease?

PMID- 7735580
TI  - Which index of peak expiratory flow is most useful in the management of stable
      asthma?
AB  - Calculation of diurnal peak expiratory flow (PEF) variability using values before
      and after bronchodilator is no longer possible for many asthmatic patients
      because they now use beta-agonists "as needed" for symptoms rather than
      regularly. This study assesses the usefulness of a number of alternative PEF
      indices as markers of airway liability in subjects with stable, although not
      necessarily well-controlled, asthma. Forty-six adult subjects completed a
      questionnaire about symptoms and treatment in the previous 3 mo. Spirometric
      function and airway hyperresponsiveness (AHR) were assessed; AHR was expressed as
      dose response ratio (DRR) (maximal percent fall in FEV1 divided by final dose of
      histamine). Subjects recorded PEF morning and evening, before and after
      bronchodilator (if used) for 2 wk. Nine different PEF indices were calculated.
      Diurnal variability (amplitude percent maximum) without bronchodilator was
      significantly less than diurnal variability with bronchodilator. Normal indices
      of PEF lability were found in 42% of subjects with reduced maximal midexpiratory
      flow (MMEF). Most of the PEF indices correlated strongly with DRR, and less
      strongly with symptom score and airway obstruction. Minimum morning
      prebronchodilator PEF over a week (expressed as percent recent best or percent
      predicted) is recommended as the best PEF index of airway lability in patients
      with stable asthma because it correlates strongly with AHR, patients are more
      likely to comply with a once-daily reading, the calculation is simple, and
      regular use of a beta-agonist is not required.

PMID- 7735581
TI  - The effect of aspirin desensitization on urinary leukotriene E4 concentrations in
      aspirin-sensitive asthma.
AB  - Patients with aspirin sensitive asthma (ASA) can be desensitized to aspirin but
      the mechanisms by which this happens are unknown. To test the hypothesis that
      there may be a reduction in aspirin-induced leukotriene release following aspirin
      desensitization, we studied nine patients with ASA, 37 +/- 2.3 yr of age (mean +/
      SEM) with a baseline FEV1 of 94 +/- 3.5%. Urinary leukotriene E4 (LTE4) and FEV1
      were measured before and after ingestion of a threshold dose of aspirin leading
      to a 15% decrease in FEV1, and then at intervals following desensitization, when
      a maintenance dose of 600 mg aspirin was ingested. Prior to desensitization, the
      maximum decrease in FEV1 following ingestion of a threshold dose of aspirin was
      15.3 +/- 3.9%, and urinary LTE4 rose from a baseline value of 235 +/- 79.4 pg/mg
      creatinine to 1,714 +/- 783 pg/mg creatinine at 3 h. Immediately after acute
      desensitization, which was performed over several days, 600 mg aspirin provoked a
      maximum decrease in FEV1 of only 3.3 +/- 2.4%, and urinary LTE4 increased from a
      baseline of 645 +/- 223 pg/mg creatinine to 1,256 +/- 456 pg/mg creatinine.
      Following ingestion of 600 mg aspirin for 9 +/- 3.2 mo (n = 5; chronic
      desensitization), urinary LTE4 rose from a basal level of 432 +/- 127 pg/mg
      creatinine to 749 +/- 257 pg/mg creatinine at 3 h after 600 mg aspirin, and this
      was accompanied by a maximum decrease in FEV1 of 7.4 +/- 4.5%. Although there was
      significantly less aspirin-induced LTE4 excretion after acute desensitization,
      substantial amounts of LTE4 were still produced without any significant change in
      lung function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735582
TI  - Effect of a novel potent platelet-activating factor antagonist, modipafant, in
      clinical asthma.
AB  - Platelet-activating factor (PAF), proposed as an important inflammatory mediator
      in asthma, reproduces several of the features of asthma, such as microvascular
      leakage, mucus secretion, bronchoconstriction, and possibly increased airway
      responsiveness. Modipafant (UK-80,067) is the (+)-enantiomer of UK-74,505, a
      potent and specific PAF antagonist. We have assessed the effect of modipafant
      over 28 d in adult subjects with moderately severe asthma in a placebo-controlled
      parallel group study. A total of 218 patients with asthma were enrolled into the
      single-blind run-in, of whom 120 (93 males and 27 females, mean age 41.0 yr)
      entered the double-blind treatment phase after demonstrating symptomatic asthma
      in the final week of the single-blind run-in phase. Patients could take up to
      1600 micrograms inhaled corticosteroid and an inhaled beta 2 agonist as rescue
      medication. A total of 59 patients with asthma took modipafant (one 50 mg capsule
      twice daily), and 61 took matched placebo. There was no significant difference
      between placebo and modipafant in diurnal variation in PEF, morning and evening
      PEF, clinic FEV1, rescue bronchodilator usage, symptom score, or airway
      responsiveness. We previously showed that the racemate UK-74,505 had no effect on
      antigen challenge, and this study shows that the active (+)-enantiomer modipafant
      has no effect in chronic asthma. This suggests that PAF is not an important
      mediator in asthma.

PMID- 7735583
TI  - Ozone exposure has both a priming effect on allergen-induced responses and an
      intrinsic inflammatory action in the nasal airways of perennially allergic
      asthmatics.
AB  - Ozone may play a significant role in the exacerbation of airway disease in
      asthmatics, either by priming the airway mucosa such that cellular responses to
      allergen are enhanced or by exerting an intrinsic effect on airway inflammation.
      Previous investigations of nonasthmatic subjects revealed that ozone induces both
      nasal and bronchial inflammation, suggesting that nasal responses to ozone may be
      used as a surrogate marker for the effect of this pollutant on bronchial mucosal
      inflammation. In this study, the effect of exposure to 0.4 ppm ozone on nasal
      inflammation in 11 allergic asthmatics sensitive to Dermatophygoides farinae was
      examined. This study was designed such that the effect of ozone exposure on the
      late-phase reaction to allergen was emphasized, using eosinophil influx and
      changes in eosinophil cationic protein as principal endpoints. By employing a
      "split-nose" design, in which allergen was applied to only one side of the nose
      while saline was applied to the contralateral side, both the effect of ozone on
      nasal inflammation due to allergen challenge as well as its direct action on non
      allergen-challenged nasal tissues was examined. The results reported herein
      indicate that ozone exposure has both a priming effect on allergen-induced
      responses as well as an intrinsic inflammatory action in the nasal airways of
      perennially allergic asthmatics.

PMID- 7735584
TI  - Circulating interleukin-6 levels in patients with bronchial asthma.
AB  - Circulating interleukin-6 (IL-6) levels were determined using a sensitive enzyme
      immunoassay in adults with asthma in stable condition during naturally occurring
      attacks and before and after allergen inhalation tests. IL-6 was significantly
      elevated even in asymptomatic asthmatic subjects (n = 17) compared with normal
      control subjects (n = 17). During naturally occurring asthmatic attacks, serum IL
      6 levels were significantly elevated in comparison with those in a symptom-free
      condition (4 wk interval; n = 8, p < 0.01). No significant difference was
      observed in serum IL-6 levels obtained from control asymptomatic asthmatic
      subjects during the period (n = 10). There was a significant elevation in
      circulating IL-6 levels in eight asthmatic patients following inhalation of
      allergen but not methacholine. These results suggest that IL-6 is involved in the
      pathophysiology of bronchial asthma.

PMID- 7735585
TI  - Radiologic evaluation of emphysema in patients with chronic obstructive pulmonary
      disease. Chest radiography versus high resolution computed tomography.
AB  - To objectively reappraise the role of the chest radiograph (CXR) in the clinical
      assessment of emphysema, we compared a standardized reading of CXR with both a
      visual scoring and a quantitative analysis of high resolution computed tomography
      (HRCT) of the chest in 46 consecutive patients with chronic obstructive pulmonary
      disease (COPD) and fixed expiratory airflow limitation. CXR were scored for signs
      of overinflation and pulmonary vascular deficiency by three independent
      observers. HRCT scans were independently scored for extent of emphysema and for
      both severity and extent of emphysema. In 28 of 46 patients, inspiratory and
      expiratory HRCT scans were analyzed quantitatively by measuring the mean CT
      number in Hounsfield Units (HU) and the percentage of lung area with CT numbers <
      -900 HU. Quantitative CT data were compared with reference values obtained in
      seven normal nonsmokers. The CXR score of emphysema showed a highly significant
      interobserver reproducibility and correlated linearly (p < 0.001) with HRCT
      visual scores and quantitative data from both inspiratory and expiratory CT scan.
      CXR score correlated with functional indices of airflow obstruction,
      overinflation, and impaired lung diffusing capacity in a way comparable to that
      obtained by using qualitative and quantitative CT data. Patients with no signs of
      emphysema on CXR had mean expiratory CT numbers within normal range and a
      fraction of lung area with CT numbers < -900 HU on expiratory scan not exceeding
      15% of total cross-sectional area. The latter value was consistently greater than
      15% in patients with CXR score > 0.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735586
TI  - Cigarette smoking and ethane exhalation in humans.
AB  - The time course of exhaled ethane gas was determined in the alveolar expirate of
      healthy, fasting smokers and nonsmokers after smoking a cigarette. Baseline
      ethane was measured by gas chromatography and corrected for background ethane
      after a 2-min washout using purified air. Ethane was measured immediately after
      smoking and hourly thereafter. Ethane was highest immediately after smoking,
      reflecting ethane in cigarette smoke. An exponential decline of ethane in smokers
      returned ethane to baseline within 3 h. Ethane in nonsmokers also peaked
      immediately after smoking but returned to baseline by 1 h. Ethane from smokers,
      measured 3 h after the last cigarette, was compared with ethane from healthy ex
      smokers and nonsmokers. Mean (+/- SEM) baseline ethane in smokers was 2.90 +/-
      0.52 pmol/min/kg, 1.55 +/- 0.36 pmol/min/kg in ex-smokers and 1.11 +/- 0.26
      pmol/min/kg in nonsmokers (p < 0.05). Ethane in two smokers measured before and
      after a week of oral beta carotene supplementation (60 mg/d) fell by 80 and 35%.
      We conclude that cigarette smokers have increased baseline ethane in exhaled
      breath compared with non-smokers. Trials with antioxidant agents are warranted to
      assess their ability to reduce expired ethane levels.

PMID- 7735587
TI  - Measurement of emphysema in autopsy lungs, with emphasis on interlobar
      differences.
AB  - This study clarifies interlobar differences in the severity of emphysema and
      examines the feasibility of assessing emphysema in a whole lung using either the
      upper or lower lobes. Midsagittal, paper-mounted whole-lung sections from 79
      consecutive autopsies were used. The whole-lung sections were scored by comparing
      them with the panel of standard pictures from Grades 0 to 100, after which the
      upper or lower lobes were scored in the same way but with the other lobe covered.
      Scores made on lobes and whole lungs correlated significantly, but while
      projections to whole-lung scores were quite accurate from the upper lobe, the
      projections from the lower lobe were less precise. This was particularly true in
      patients with mild emphysema. Individual lobes of the same lung sections were
      assessed by the Ryder grid method. This analysis showed that emphysema was more
      severe in the upper lobe of the 79 consecutive cases. The panel grading method
      showed more severe emphysema in the upper lobe than in the lower lobe to a panel
      score of 40; after this, the severity of emphysema in the two lobes was similar.
      Scores made from the Ryder grid were very similar to those made from the panel.
      Grading emphysema from one lobe, particularly the lower lobe, is not appropriate
      if precise clinicopathologic correlations are required.

PMID- 7735588
TI  - Airway hyperresponsiveness to histamine associated with accelerated decline in
      FEV1.
AB  - An increased level of airway responsiveness has been proposed as a risk factor
      associated with the onset and prognosis of chronic airway obstruction. To
      determine this, longitudinal studies are necessary, with measurement of both the
      level of airway responsiveness and of additional risk factors, such as cigarette
      smoking, made before measurement of pulmonary function decline. The association
      of airways responsiveness with decline in FEV1 has been prospectively studied in
      a random sample of the Dutch population. Longitudinal data from 921 males,
      providing 2,376 paired observations, and 698 females, providing 1,682 paired
      observations, were used for analysis. Differences between responders and
      nonresponders (PC10 < or = 16 mg/ml of histamine) were estimated from linear
      regression analyses stratified by gender and smoking status, with adjustment for
      age, residential area, the presence of respiratory symptoms, indicators for each
      interval, and residuals of FEV1 at the beginning of the interval. Responders had
      a greater mean yearly decline in FEV1, and the differences between responders and
      nonresponders were similar for all gender and smoking subgroups. In an overall
      regression model, subjects with airway hyperresponsiveness had a significantly
      steeper decline in FEV1, independent of the other variables (males: beta = -12.5
      ml/yr, SEM = 3.22, p < 0.001; females: beta = -11.50 ml/yr, SEM = 2.98, p <
      0.001). The current analyses conclusively demonstrated that increased airway
      responsiveness is an independent risk factor for an accelerated decline in FEV1
      and, hence, for the development of chronic obstructive lung disease. The
      mechanisms by which increased airway responsiveness leads to an accelerated
      decline in FEV, are imperfectly understood and require further study.

PMID- 7735589
TI  - Dietary antioxidant vitamin intake and lung function in the general population.
AB  - We have investigated the relation between lung function and dietary intake of the
      antioxidant vitamins C and E in the general population in a cross-sectional
      survey of a random sample of adults from the electoral register of an
      administrative area of Nottingham. In 2,633 subjects 18 to 70 yr of age, we
      measured FEV1 and FVC, allergen skin sensitivity to grass pollen, cat fur, and
      Dermatophagoides pteronyssinus, pack-years smoking exposure by personal recall,
      and usual dietary intake of vitamins C and E by semiquantitative food frequency
      questionnaire. After adjustment for the effects of age, sex, height, mean
      allergen skin wheal diameter, and pack-years smoking history, both FEV1 and FVC
      were significantly and independently related to mean daily intake of vitamin C,
      such that a standard deviation (40 mg/d) higher vitamin C intake was associated
      with a 25.0 (95% CI, 5.2 to 44.8; p = 0.01) ml higher FEV1 and a 23.3 (0.94 to
      45.7, p = 0.04) ml higher FVC. There was also an association between vitamin E
      intake and lung function, such that a standard deviation (2.2 mg) higher intake
      of vitamin E was associated with a 20.1 (1.3 to 40.4, p = 0.04) ml higher FEV1
      and a 23.1 (1.0 to 45, p = 0.04) ml higher FVC. However, vitamin C and vitamin E
      intakes were significantly correlated (r = 0.29, p < 0.001), and after allowing
      for the effects of vitamin C there was no additional independent effect of
      vitamin E on either FEV1 or FVC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735590
TI  - Association of asthma with serum IgE and skin test reactivity to allergens among
      children living at high altitude. Tickling the dragon's breath.
AB  - Asthma in children and young adults is strongly associated with immediate
      hypersensitivity to indoor allergens, notably those derived from the house dust
      mite. In addition, outdoor air pollution is considered to aggravate existing
      asthma. We investigated the prevalence of asthma and the pattern of allergen
      sensitization in a mite-free environment with low levels of outdoor air
      pollution. A total of 567 children aged between 12 and 14 attending Los Alamos
      Middle School, NM (altitude 7,200 feet) were screened using a respiratory
      questionnaire; 120 children (53 control children) underwent allergen skin testing
      and serum IgE measurement, and their bronchial reactivity to histamine was
      measured. Dust was collected from 111 homes and the level of indoor mite and cat
      allergen measured. The prevalence of respiratory symptoms was high (13%), and
      from the detailed testing it was estimated that 6.3% of the children had asthma
      (defined as symptomatic bronchial reactivity). Children with asthma had elevated
      IgE, 367 (179 to 755) versus 38 (23 to 61), and predominant sensitization to cat,
      68 versus 20% (p < 0.001). A high number of households (77%) had a pet cat or
      dog. The concentration of mite allergen was very low (mean 0.18 micrograms Der p
      milligrams sieved house dust), whereas that of cat allergen was high in homes
      with a cat (80.8 micrograms Fel d milligrams) but also in homes with no cat (3.2
      micrograms Fel d milligrams). The results show that in a mite-free environment
      with low levels of outdoor air pollution, asthma was still a major cause of
      morbidity among schoolchildren.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735591
TI  - Effects of cigarette smoking on lung function in four population samples in the
      People's Republic of China. The PRC-US Cardiovascular and Cardiopulmonary
      Epidemiology Research Group.
AB  - As part of an ongoing study of cardiopulmonary risk factors in the People's
      Republic of China, we conducted lung function tests and obtained information
      about smoking habits on 6,765 Chinese men and women 35 to 56 yr of age residing
      in or around Beijing in the north and in or around Guangzhou in the south. Within
      each region, separate urban and rural populations were recruited. This study
      examined the relationship between tobacco consumption (both manufactured
      cigarettes and leaf tobacco) and lung function in a subset of current smokers and
      never smokers who had acceptable lung function data. All methods were strictly
      standardized. Overall, tobacco smoking was associated with a statistically
      significant mean difference in FEV1 among men (-89 ml) and women (-52 ml)
      relative to never smokers after adjusting for age, height, and residence.
      Differences between smokers of cigarettes and smokers of leaf tobacco were not
      significant. Among the subset of smokers who smoked only cigarettes, this
      decrement increased with increasing duration of cigarette smoking, but it was
      small (-4 ml/yr of smoking for FEV1 for both men and women) in comparison with
      the effects of smoking reported from western countries. Although the smoking
      effect tended to increase with increasing dose, these differences were small and
      generally not statistically significant. The relatively small smoking effect in
      this study may result from differences between developed and developing countries
      in the cumulative dose of tobacco products. Alternative explanations or
      contributing factors such as racial differences in susceptibility and differences
      in the form and delivery of tobacco cannot be discounted.

PMID- 7735592
TI  - A prospective study of diet and adult-onset asthma.
AB  - A role for diet in the pathophysiology of asthma may be mediated by altered
      immune or antioxidant activity with consequent effects on airway inflammation. We
      evaluated associations between several dietary factors assessed by a
      semiquantitative food frequency questionnaire, and incidence of asthma over a 10
      yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of
      vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95%
      confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest
      quintile. This relationship, however, was attenuated when the contribution from
      nuts, a major source of vitamin E in these data and a possible allergen, was
      removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive
      associations were found for vitamins C and E from supplements, but appeared to be
      explained by women at high risk of asthma initiating use of vitamin supplements
      prior to diagnosis. A nonsignificant inverse association with carotene intake was
      noted, but no clear relations with asthma were demonstrated for intake of
      linoleic acid or omega-3 fatty acids. These data suggest that antioxidant
      supplementation and intake of various fats during adulthood are not important
      determinants of asthma, although vitamin E from diet may have a modest protective
      effect.

PMID- 7735593
TI  - Enhanced retention of asbestos fibers in the airways of human smokers.
AB  - To determine whether cigarette smoke increases the pulmonary retention of
      asbestos, we compared the asbestos-fiber burden in the airway mucosa of six
      cigarette smokers who had received heavy occupational asbestos exposure with that
      in a group of six subjects with similar exposure who were never smokers. The
      groups were matched in terms of age, sex, years of exposure, and mean parenchymal
      amosite burden. We found that the concentration of amosite in airway mucosa was
      significantly elevated (by approximately sixfold) in smokers (p < 0.02).
      Chrysotile parenchymal burdens were statistically similar in both groups, but the
      chrysotile airway burden was again higher (by approximately 50-fold) in smokers
      (p < 0.006). There were no differences in airway or parenchymal tremolite burdens
      between the two groups. Fibers of all three types of asbestos recovered from the
      airway mucosa or parenchyma of smokers were shorter than fibers recovered from
      nonsmokers, an observation in accord with experimental data suggesting that
      cigarette smoke leads to retention of shorter fibers. These findings indicate
      that cigarette smoking causes enhanced accumulation of both amosite and
      chrysotile in the airway mucosa. This process may play a role in potentiating the
      pathologic effects of asbestos.

PMID- 7735594
TI  - Effect of inhaled nitric oxide on right ventricular function in adult respiratory
      distress syndrome.
AB  - To determine whether inhaled nitric oxide (NO) affects pulmonary circulation,
      thereby improving right ventricular (RV) function in adult respiratory distress
      syndrome (ARDS), we studied 13 patients with both a lung injury severity score of
      2.5 or more and a mean pulmonary artery pressure higher than 30 mm Hg. RV
      function was assessed by a thermodilution technique using a pulmonary artery
      catheter equipped with a rapid response thermistor before and 15 min after
      initiation of inhalation of NO (5 ppm). At baseline, stroke volumes were in a
      normal range (46 +/- 14 ml/m2), with a RV dilation (end-diastolic volume = 142 +/
      36 ml/m2). Inhaled NO was followed by an improvement in arterial oxygenation
      (PaO2/FIO2 = 103 +/- 47 versus 142 +/- 63, p < 0.05) and a drop in pulmonary
      artery pressure (36.1 +/- 4.5 versus 31.3 +/- 6.1 mm Hg, p < 0.01); stroke
      volumes and heart rates did not change. The resulting fall in pulmonary vascular
      resistance (211 +/- 43 versus 180 +/- 59 dyn-s/cm5, p < 0.05) was associated with
      an increase in RV, ejection fractions (32 +/- 5 versus 36 +/- 6%, p < 0.05), a
      trend toward decreased RV end-systolic (96 +/- 25 versus 85 +/- 19 ml/m2, NS) and
      end-diastolic (142 +/- 36 versus 131 +/- 27 ml/m2, NS) volumes, and a decrease in
      right atrial pressures (10.9 +/- 2.9 versus 9.6 +/- 3.2 mm Hg, p < 0.05). No
      relationship was seen between the improvement in arterial oxygenation and the
      decrease in pulmonary vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735595
TI  - Circulating ICAM-1 is increased in septic shock.
AB  - Adhesion molecules play a critical role in the interaction of circulating
      neutrophils with vascular endothelium during inflammation. Increased quantities
      of soluble, circulating intercellular adhesion molecule-1 (cICAM-1) are present
      in various inflammatory conditions. The purpose of this investigation was to
      measure cICAM-1 levels in septic adults, as well as to examine the relationship
      between this potential marker of endothelial-cell activation and the consequences
      of sepsis (i.e., multiple organ failure and death). Using a sandwich-type enzyme
      linked immunosorbent assay (ELISA), we measured cICAM-1 in blood samples obtained
      within 12 h of admission to an intensive care unit (ICU) for sepsis and other
      conditions. We found cICAM-1 levels to be increased in 25 septic patients (1,259
      +/- 159 ng/ml, mean +/- SEM) as compared with 12 healthy volunteers (355 +/- 41
      ng/ml, p < 0.0001) and four ICU patients without systemic inflammatory response
      syndrome (SIRS) (585 +/- 76 ng/ml, p < 0.001). Twenty-five patients with SIRS but
      no evidence of causative infection also had elevated levels of cICAM-1 (937 +/-
      144 ng/ml, p = 0.12 versus sepsis). Serial measurements over the first week of
      sepsis demonstrated persistent elevation in most patients. Day 1 cICAM-1 levels
      were higher (p = 0.017, ANOVA) in 16 patients with septic shock than in seven
      with severe sepsis and two with sepsis but without hypotension or hypoperfusion.
      There was a positive correlation (r = 0.50, p = 0.009) between Day-1 cICAM-1
      measurements and severity of shock as determined by the presence of hypotension
      and vasopressor use.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735596
TI  - Plasma elastase levels and the development of the adult respiratory distress
      syndrome.
AB  - Inflammatory cells, particularly neutrophil granulocytes, have been implicated in
      the pathogenesis of the adult respiratory distress syndrome (ARDS). In this
      study, we investigated whether a relationship exists between neutrophil elastase
      in the plasma of multiple-trauma patients on initial hospital presentation and
      the subsequent development of lung injury and ARDS. Sixty-one multiple-trauma
      patients were enrolled prospectively. Neutrophil elastase was measured by a
      specific radioimmunoassay, and analysis was performed by nonparametric
      statistical methods. A highly significantly elevated plasma elastase level was
      found in patients who progressed to ARDS (median 217 ng/ml, range 127 to 480) (n
      = 8) compared with those who did not (median 117 ng/ml, range 21.4 to 685) (n =
      53) (p = 0.009). Significant correlation was found between initial elastase
      values and subsequent requirement for mechanical ventilation (p = 0.01), lowest
      arterial oxygen saturation/oxygen supplementation recorded (p = 0.003), and organ
      failure score (p = 0.006). This study shows that within minutes of the initiating
      trauma event, there is evidence of enhanced neutrophil degranulation as
      manifested by elevated levels of immunoreactive neutrophil elastase in the
      peripheral blood. The level of this enzyme correlates with the degree of
      subsequent lung injury and ARDS. These findings reinforce the importance of
      neutrophils and their secretory products in early ARDS disease pathogenesis.

PMID- 7735597
TI  - Bronchial responsiveness in the neonatal period as a risk factor for wheezing in
      infancy.
AB  - Bronchial responsiveness is closely associated with asthma in schoolchildren. We
      wished to test the hypothesis that bronchial responsiveness in the neonatal
      period might be a risk factor for lower-respiratory illnesses (LRI), typically
      cough and wheezing with viral infection, in infants. A cohort of 73 full-term
      healthy infants of atopic parents were observed during the first year of life.
      Respiratory illness was recorded and ascertained retrospectively by
      questionnaires administered to parents at 6-mo intervals, and infants were
      classified as having: LRI (one or more episode of wheezing in the first year) or
      no LRI (no wheezing). At approximately 1 mo of age, lung function was measured
      under sedation, and bronchial responsiveness (BR) to histamine aerosol was
      determined and expressed as PC30, the provocative concentration of histamine that
      induced a 30% decrease in maximum flow at FRC (V'maxFRC) by the squeeze
      technique. For the whole group, no index of lung function predicted subsequent
      wheezing. Among boys, however, there was a trend toward a lower V'maxFRC in those
      who subsequently developed LRI than in the group without LRI (median values 62
      versus 98 ml/s; 95% CI: -1 to 68; p = 0.06), while among girls the major
      difference was in PC30, for which those who subsequently had LRI were
      significantly more responsive as neonates (PC30 was lower) than the group without
      LRI (1.4 versus 8.3 g/L; 95% CI: 1.0 to 13.1; p < 0.05). These findings suggest
      that sex differences in airway structure and responsiveness present soon after
      birth, and representing differences in fetal lung development, are associated
      with differences in the risk of subsequent LRI with wheezing.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7735598
TI  - A new technique to generate and assess forced expiration from raised lung volume
      in infants.
AB  - We have developed a new technique that allows assessment of infant lung function
      over an extended volume range. The lungs are rapidly inflated to a predetermined
      inflation pressure (PP) using a modified diaphragm pump. Forced expiratory flow
      volume (FEFV) curves are then generated from raised lung volumes using an
      inflatable plastic jacket. We studied 26 normal infants with a median age of 14
      mo (range, 3 to 23 mo). FEFV curves were obtained in each infant from end-tidal
      inspiration and from lung volumes set by a range of PP (15 to 20 cm H2O). Mean
      (SE) volume above FRC was 107 ml (9 ml), and mean forced expiratory time was 0.73
      s (0.05 s) at end-tidal inspiration. Both measurements increased progressively
      with increases in PP to 251 ml (13 ml) and 1.04 s (0.06 s), respectively, at 20
      cm H2O PP (p < 0.0001). Mean intrasubject coefficient of variation was 15.5% (95%
      confidence interval, 12 to 19%) for maximal flow at FRC, but it was less than 6%
      (95% CI, 4 to 8%) for forced expiratory volume-time (FEVt) measurements at all
      levels of PP. Twenty-seven recurrently wheezy infants with a median age of 13 mo
      (range, 6 to 18 mo) were subsequently studied using a PP of 17.5 cm H2O. Wheezy
      infants had a lower VmaxFRC [mean (1.39 ml/s/cm) and 95% CI (1.15 to 1.63
      ml/s/cm)] than did normal infants (1.78 ml/s/cm; CI, 1.51 to 2.05) (p < 0.05).
      FEV1 measurements were all lower in wheezy infants than in normals infants: mean
      FEV0.5, 1.86 ml/cm (CI, 1.73 to 1.98) and 2.31 ml/cm (CI, 2.15 to 2.48),
      respectively (p < 0.0001); FEV0.75, 2.20 ml/cm (CI, 2.07 to 2.32) and 2.72 ml/cm
      (CI, 2.52 to 2.91), respectively (p < 0.0001); FEV1.0, 2.42 ml/cm (CI, 2.26 to
      2.58) and 2.84 ml/cm (CI, 2.63 to 3.06), respectively (p < 0.005). The Ci values
      of each FEVt measurement did not overlap between the wheezy and normal groups;
      however, the CI values of VmaxFRC overlapped markedly. In addition, FEVt
      parameters showed greater sensitivity in detecting reduced lung function (71 to
      89%) than did VmaxFRC parameters (56%). We conclude that (1) FEVt measurements
      derived from a lung volume set by a standardized pressure are more reproducible
      than flow measurements in the tidal volume range; (2) FEVt measurements are
      significantly lower in wheezy infants than in normal infants, show less overlap
      than flow measurements in the tidal volume range, and therefore are better able
      to separate the two populations.

PMID- 7735599
TI  - Comparison of single-breath and plethysmographic measurements of resistance in
      infancy.
AB  - Single-breath technique (SBT) measurements of total respiratory resistance (Rrs)
      were compared with plethysmographic measurements of airway resistance (Raw) in
      healthy infants < or = 13 wk of age (Group 1; n = 49) and > 13 wk of age (Group
      2; n = 37) and in infants > 13 wk of age with prior wheeze (Group 3; n = 49). A
      significantly higher percentage of Rrs (19%) than of Raw (2%) measurements were
      technically unsatisfactory, alinearity of the flow-volume curve accounting for
      54% of Rrs failures. Although both Rrs and Raw were significantly higher in Group
      3 infants, between-subject variability was wide in all groups. Rrs was
      significantly higher than initial expiratory (IE) Raw in all groups. Mean
      difference Rrs-IE Raw (95% CI) values were 1.98 (1.51, 2.48), 1.29 (0.96, 1.62),
      and 1.97 (1.56, 2.38) kPa.L-1.s for Groups 1, 2, and 3, respectively. Significant
      but smaller differences were seen for end-expiratory (EE) Raw in Groups 1 and 2
      but not in Group 3. Mean difference Rrs-EE Raw (95% CI) values were 0.68 (0.11,
      1.26), 0.55 (0.19, 0.92), and 0.31 (-0.06, 0.69) kPa.L-1.s for Groups 1, 2, and
      3, respectively. Despite wide between-subject variability in Rrs and a relatively
      high failure rate, the SBT is simple to use, and it may be applicable to
      epidemiologic studies. However, clinical applications in individual infants may
      be limited by failure to detect the dynamic changes in resistance throughout the
      breath evident from plethysmographic studies.

PMID- 7735600
TI  - Snoring and sleep apnea. A population study in Australian men.
AB  - Snoring and sleeping apnea are reportedly associated with morbidity. We used home
      monitoring (MESAM IV) to measure snoring and sleep apnea in 294 men aged 40 to 65
      yr from the volunteer register of the Busselton (Australia) Health Survey. In
      this group, 81% snored for more than 10% of the night and 22% for more than half
      the night; 26% had a respiratory disturbance index (RDI) > or = 5, and 10% had an
      RDI > or = 10. There was a relatively low correlation between percentage of night
      spent snoring and RDI (rho = 0.47, p < 0.005). Subjective daytime sleepiness plus
      RDI > or = 5 occurred in a minimum of 3%. Obesity was related to snoring, RDI,
      and minimum SaO2 (all p < 0.0001). There was no relationship between age and
      either RDI or snoring, but increased age was related to minimum SaO2 < 85% (p <
      0.05). Alcohol consumption was not related to sleep-disordered breathing. Smokers
      snored for a greater percentage of the night than nonsmokers (41 versus 31%, p =
      0.01). We conclude that, in middle-aged men, both snoring and sleep apnea are
      extremely common, and in this age range both are associated with obesity but not
      with age. However, a high percentage of snoring is not essential for the
      occurrence of sleep apnea, nor does it necessarily indicate that apnea is
      present.

PMID- 7735601
TI  - Electrical activation of the expiratory muscles to restore cough.
AB  - Many patients with spinal cord injury have paralysis of their expiratory muscles
      and, consequently, lack an effective cough. The purpose of the present study was
      to evaluate the utility of lower thoracic spinal cord stimulation (SCS) to
      activate the expiratory muscles. Studies were performed on 15 anesthetized dogs.
      A quadripolar stimulating electrode (Medtronic Model 3586) was inserted
      epidurally and on the ventral surface of the lower thoracic spinal cord. Changes
      in airway pressure, airflow, and internal intercostal and abdominal muscle length
      were monitored to assess the effects of electrical stimulation. Spinal
      stimulation applied at the T9-T10 spinal level provided maximal changes in airway
      pressure generation in preliminary experiments. All subsequent studies were
      therefore performed with the electrode positioned at this level. The expiratory
      muscles were stimulated supramaximally over a wide range of lung volumes which
      were expressed as the corresponding change in airway pressure. The pressure
      generating capacity of the expiratory muscles was evaluated by the change in
      airway pressure produced by SCS during airway occlusion. Peak expiratory airflow
      was also monitored following release of occlusion. At FRC, deflation (-10 cm H2O)
      and inflation (+ 30 cm H2O), SCS resulted in positive airway pressures of 44 cm
      H2O +/- 4 SE, 28 cm H2O +/- 3 SE, and 82 cm H2O +/- 7 SE. The relationship
      between airway pressure expiratory airflow generation and lung volume was linear
      (slope = 1.34 +/- 0.04) over the entire vital capacity range. Our results
      indicate that: (1) a major portion of the expiratory muscles can be activated
      reproducibly and in concert by electrical stimulation, and (2) this technique may
      be a clinically useful method of restoring cough in spinal cord injured patients.

PMID- 7735602
TI  - Exercise capacity as a predictor of postoperative complications in lung resection
      candidates.
AB  - Exercise testing with measurement of maximal oxygen uptake (VO2max) is
      increasingly used in the assessment of lung resection candidates, but its
      predictive value for postoperative complications remains controversial. We
      therefore sought to determine the prognostic value of VO2max compared with other
      pulmonary function tests. A consecutive group of 80 patients (mean age 61 yr; 57
      males and 23 females) scheduled for lung resection (62 malignancies, 12 benign
      disorders, and 6 carcinoids) underwent pulmonary function tests and symptom
      limited cycle ergometry. All patients underwent lung resections: 21
      pneumonectomies, 45 lobectomies, and 14 segmental or wedge resections. Group A
      (64 patients, 80%) had an uneventful postoperative course, whereas Group B (16
      patients, 20%) had complications; 3 of them died (4% overall mortality rate). In
      a stepwise logistic regression analysis used to determine independent risk
      factors for postoperative complications (within 30 d), VO2max expressed as a
      percentage of predicted (84 +/- 19 for Group A versus 61 +/- 11 for Group B)
      proved to be the best predictor (predictive value 85.5%). Although VO2max
      expressed in absolute values (ml/kg/min) was also highly predictive (79.5%), a
      ROC curve analysis proved the percentage predicted values to be significantly
      more sensitive. Of 9 patients with a VO2max < 60% of predicted, 8 had
      complications, including all 3 patients who died after resections of more than
      one lobe (sensitivity 50%, specificity 98%). The estimated probability (probit
      model SAS software package) of suffering no complication was 0.9 for VO2max > 75%
      of predicted and 0.1 for a VO2max < 43%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735603
TI  - Rib cage distortion in a canine model of flail chest.
AB  - Although blunt chest injuries frequently lead to respiratory failure, the effects
      of flail chest on the mechanics of breathing have not been evaluated. In the
      present studies, we have measured the respiratory displacements of the ribs and
      sternum and the electromyograms (EMG) of the parasternal and external intercostal
      muscles in eight supine, anesthetized, spontaneously breathing dogs before and
      after the third to sixth ribs on the right side of the chest were fractured both
      dorsally and ventrally. After flail, the fractured ribs moved inward, rather than
      outward, during inspiration, but their inspiratory cranial displacement remained
      unchanged. The inspiratory outward and caudal displacement of the sternum, the
      inspiratory EMG activity of the parasternal intercostals, the pattern of
      breathing, and the arterial blood gases were also unaltered. However, the
      inspiratory EMG activity recorded from the external intercostals increased
      consistently to 327 +/- 101% of control (p < 0.05). These observations indicate
      that with flail chest, the disconnected segment of the rib cage shows paradoxical
      motion exclusively along the lateral axis; the increased external intercostal
      activation may account, at least in part, for the persistent inspiratory cranial
      motion of the ribs. These observations also suggest that the harmful effects of
      blunt chest injuries are related to pulmonary contusion and pain, rather than to
      flail chest per se.

PMID- 7735604
TI  - Comprehensive tuberculosis control for patients at high risk for noncompliance.
AB  - The current tuberculosis epidemic in the United States is marked, in many areas,
      by high rates of noncompliance with antituberculous regimens. In response to
      this, a comprehensive program of medical, nursing, social services, and
      supervised therapy was developed at Bellevue Hospital. Most patients were
      referred to the on-site directly observed therapy program (DOT) located in the
      hospital. Patients on DOT received daily or twice weekly therapy, and were given
      incentives to enhance compliance. Outreach was used to track patients who missed
      appointments. From November 1992 through July 1993, 113 patients were referred.
      HIV infection, homelessness, illicit drug use, and alcoholism were common. Follow
      up revealed that 11 patients were noncompliant and completely lost to follow-up;
      of the remaining 102, 99% achieved bacteriologic cure. Of the 102 patients who
      received therapy, 74 attended the Bellevue DOT clinic, 16 attended other DOT
      programs in the city or received medication at home, and three died of HIV
      related, nontuberculous illness. Nine patients were self-medicated and judged
      treatment successes. We conclude that a comprehensive hospital-based tuberculosis
      control program is capable of achieving a high degree of success, even in a
      population at high risk for noncompliance.

PMID- 7735605
TI  - Efficacy, safety, and therapeutic relevance of transthoracic aspiration with
      ultrathin needle in nonventilated nosocomial pneumonia.
AB  - In order to determine the potential indications of transthoracic needle
      aspiration (TNA) using the ultrathin 25G needle for the diagnosis of
      nonopportunistic lung infections, we prospectively analyzed the diagnostic
      efficacy, safety, and therapeutic implications of its results in 97 patients with
      nonventilated nosocomial pneumonias (NVNP). The sensitivity of TNA was 60.9%.
      Specificity and positive predictive value (PPV) were 100%. Negative predictive
      value (NPV) was 34.1%. The complications in the studied cases were nil in 89
      cases (91.8%), transient hemoptoic expectoration (< 10 ml) in five (5.2%), and
      self-limited partial pneumothorax in three (3.1%). No complications needing
      treatment were observed. On the basis of a positive TNA result, the initial
      antibiotic treatment was modified in 29 of 97 (29.9%) cases. In twelve of these,
      the empirical antibiotic regimen was demonstrated to be ineffective. We conclude
      that, using the 25G needle, TNA has a good diagnostic efficacy and is a safe
      procedure for the etiologic investigation of NVNP. A positive TNA result has
      significant therapeutic relevance, even in cases where broad-spectrum antibiotics
      are empirically prescribed.

PMID- 7735606
TI  - Cigarette smoke inhibits lung fibroblast proliferation and chemotaxis.
AB  - Cigarette smoking is the most clearly recognized cause of pulmonary emphysema.
      Since loss of lung tissue, which characterizes emphysema, represents a balance
      between injury and repair, we hypothesized that cigarette smoke might contribute
      to the development of emphysema by inhibiting fibroblast proliferation and
      migration. To evaluate this, we examined the effect of cigarette smoke extract
      (CSE) on the proliferation and migration of human lung fibroblasts in vitro. CSE
      inhibited fibroblast proliferation and migration at noncytotoxic concentrations.
      When CSE was treated to remove volatile components, it showed less inhibitory
      activity on fibroblast proliferation. Therefore, we also examined acrolein and
      acetaldehyde, which are volatile components of cigarette smoke, Micromolar
      concentrations of acrolein and millimolar concentrations of acetaldehyde induced
      significant inhibition of fibroblast proliferation. In contrast, removal of
      volatile components did not eliminate the inhibitory activity of CSE for
      fibroblast migration, although acetaldehyde and acrolein alone were also capable
      of inhibiting chemotaxis. Cigarette smoke-induced inhibition of fibroblast
      proliferation and migration may impair lung repair following lung injury, and may
      thus contribute to the development of pulmonary emphysema.

PMID- 7735607
TI  - Effects of nitrous acid exposure on human mucous membranes.
AB  - Nitrous acid (HONO) is formed both indirectly from the reaction of nitrogen
      dioxide (NO2) with water on indoor surfaces, and directly during combustion. This
      gaseous pollutant may be a previously unrecognized causal factor in assessments
      of nitrogen oxide exposure effects. The present study is the first attempt to
      evaluate exposure effects of HONO on the human airways and the mucous membranes
      of the eyes and nose. Fifteen healthy adult nonsmokers were exposed for 3.5 h in
      a double-blind, balanced protocol to clean air, 77, and 395 ppb HONO. Each
      exposure was preceded by a 1-h baseline measurement period, and exposures were
      separated by 1 wk. There was a 10-min exercise period during exposure. Effects
      measurements included assessment of bronchial reactivity, measurement of specific
      airway conductance, spirometry, acoustic rhinometry, nasal lavage, tear-fluid
      cytology, a CO2 eye-provocation test, evaluation of eye redness, and subjective
      sensations. Effects of HONO exposure on the eyes were found as exposure-related
      changes in tear-fluid cytology. In particular, the number of squamous cells
      increased by 20, 67, and 80% following exposure to clean air, 77, and 395 ppb
      HONO, respectively (p = 0.004). Possible indications of exposure effects on
      sensitivity to CO2 eye provocation and on specific airway conductance were also
      measured. For specific airway conductance there was an approximate 10% decrease
      in conductance following exercise in association with HONO exposure, compared
      with a 2% decrease with clean air (p = 0.038).

PMID- 7735608
TI  - Restrictive lung disease in rats exposed chronically to an urban profile of
      ozone.
AB  - The potential for irreversible lung impairment resulting from life-long ozone
      (O3) exposure remains uncertain. To address this question, young adult rats
      (male, F-344) were exposed to a simulated urban profile of O3 for 1, 3, 13, 52,
      or 78 wk, after which pulmonary function tests were performed. To assess
      reversibility of effects, cohorts from the 13-, 52-, and 78-wk groups were
      evaluated, respectively, after an additional 6, 27, and 17 wk of clean air.
      Static and dynamic lung properties were based on measurements of lung volume
      apportionment, respiratory system compliance (Crs), DLCO, multibreath N2 washout,
      and maximum expiratory flow-volume relationships. Electrocardiography was also
      performed in unanesthetized, restrained rats after 52 and 78 wk, as were
      determinations of wet and dry lung weights, lung collagen, and associated
      connective tissue crosslinks. Small (< 10%) but significant reductions in TLC and
      RV were noted after 13, 52, and 78 wk of O3 exposure. At 13 and 52 wk, N2 washout
      was enhanced, though at 78 wk it was similar to control. None of these changes
      appeared progressive with continued O3 exposure. Post exposure to clean air did
      not completely reverse the reduction in TLC. Additionally, Crs, though not
      affected during O3 exposure, decreased during the air recovery. No O3-related
      changes in collagen were apparent, however. Thus, near life-long exposure of F
      344 rats to a worse-case, urban profile of O3 appears to have led to a
      functionally restrictive, i.e. "stiffened," lung without overt fibrosis.
      Furthermore, certain aspects of the O3-induced effect were not fully reversible.

PMID- 7735609
TI  - Mechanisms of lung liquid clearance during hyperoxia in isolated rat lungs.
AB  - Sodium transport across the lung epithelium is predominantly effected by apical
      amiloride-sensitive Na+ channels and basolaterally located ouabain-sensitive Na,K
      ATPases. Previously, we reported that subacute hyperoxia caused an increase in
      active Na+ transport in rat lungs paralleling Na,K-ATPase upregulation in
      alveolar Type 2 cells isolated from the same lungs. In the present study we set
      out to quantify the amiloride-sensitive Na+ flux and ouabain-sensitive active Na+
      transport in the isolated-perfused, fluid-filled lung model from rats exposed to
      85% O2 for 7 d compared with normoxic control rats. We found increased
      transpulmonary albumin flux and permeability to small solutes (Na+ and mannitol)
      in hyperoxic rat lungs compared with controls. Amiloride (10(-5) M) instilled
      into rat airspaces inhibited active Na+ transport by approximately 62% in control
      rat lungs and by approximately 87% in lungs from rats exposed to hyperoxia,
      without further changing permeability for Na+ and mannitol. Ouabain (10(-5)M)
      perfused through the pulmonary circulation decreased active Na+ transport by
      approximately 40% in normal rat lungs and by approximately 52% in lungs from rats
      exposed to hyperoxia. We conclude that active Na+ transport and edema clearance
      are increased in the subacute hyperoxic lung injury in rats, caused in part by
      the upregulation of amiloride-sensitive apical Na+ channels and alveolar
      epithelial Na,K-ATPases. Conceivably, the upregulation of alveolar epithelial Na+
      channels and Na,K-ATPases protects against the effects of lung injury in this
      model by contributing to effective edema clearance.

PMID- 7735610
TI  - Allergen-induced oxygen radical release from bronchoalveolar lavage cells and
      airway hyperresponsiveness in dogs.
AB  - Allergen inhalation causes airway hyperresponsiveness and airway inflammation in
      dogs. The purpose of this study was to determine whether allergen-induced airway
      hyperresponsiveness is associated with increases in oxygen radical production
      from bronchoalveolar lavage (BAL) cells. A group of 10 random-source dogs were
      studied twice, 4 wk apart. On each occasion, acetylcholine (ACh) airway
      responsiveness was measured before and 24 h after inhalation of Ascaris suum or
      its diluent, followed by BAL. The response to ACh was expressed as the
      concentration causing an increase in lung resistance of 5 cm H2/O/L/s above
      baseline. Spontaneous and phorbol myristate acetate (PMA)-stimulated (2.4
      mumol/L) oxygen radical release were measured, for 10 min each, from washed BAL
      cells (4 x 10(6) cells/ml) by luminol-enhanced chemiluminescence in a luminometer
      at 37 degrees C. Superoxide anion production was measured using a cytochrome c
      assay. Allergen inhalation caused bronchoconstriction, airway inflammation, and
      airway hyperresponsiveness. The acetylcholine provocative concentration fell from
      7.47 mg/ml (% SEM 1.61) before to 1.23 mg/ml (% SEM 1.62) after allergen (p <
      0.0001). Allergen inhalation significantly increased absolute neutrophil (p =
      0.03) and eosinophil (p = 0.02) counts in BAL. Spontaneous (p < 0.0003) and PMA
      stimulated (p < 0.0005) chemiluminescence and superoxide anion production (p =
      0.039) were increased after allergen inhalation. The allergen-induced increases
      in chemiluminescence were significantly correlated with the increases in ACh
      airway hyperresponsiveness (r = 0.75, p < 0.012). These results indicate that
      inhaled allergen increases oxygen radical release from bronchoalveolar lavage
      cells and supports the hypothesis that oxygen radicals are important in causing
      allergen-induced airway hyperresponsiveness.

PMID- 7735611
TI  - Effects of cyclosporine A on skeletal muscle mitochondrial respiration and
      endurance time in rats.
AB  - We investigated the effects of 14 d of cyclosporine A (CsA) administration on
      skeletal muscle mitochondrial respiration and submaximal running endurance time
      in rats. Eight experimental (CsA) and eight control rats followed a 14-d feeding
      protocol of CsA (20 mg/kg/d) oral administration or placebo. Submaximal endurance
      exercise time (EET) was measured on a treadmill on Day 13 and mitochondria were
      isolated from the hind limb muscles homogenate on Day 15. The results showed (1)
      a significant decrease of EET in CsA versus control rats (29 +/- 8 min versus 60
      +/- min, p < 0.001), (2) significantly lower state 3 and uncoupled mitochondrial
      respiration in CsA compared with control rats with pyruvate plus malate (p <
      0.001, p < 0.01) as well as succinate plus rotenone (p < 0.01) as substrates, (3)
      no differences in coupling efficiency (ADP/O ratios), and (4) significant linear
      correlation between EET and state 3 respiration (r = 0.71, p < 0.05; r = 0.92, p
      < 0.001), and strong curvilinear relationship between EET and CsA state 3/mean
      control state 3 (r2 = 0.81, p < 0.001; r2 = 0.82, p < 0.001), respectively, with
      pyruvate plus malate and succinate plus rotenone. We conclude that 14 d of CsA
      oral administration decreases skeletal muscle mitochondrial electron chain
      capacity without changing coupling efficiency in rats. Results suggest that
      immunosuppressive therapy is responsible, in part, for poor exercise performance
      in transplant patients.

PMID- 7735612
TI  - Genetic susceptibility to atracurium-induced bronchoconstriction.
AB  - The goal of this study was to develop a murine model of atracurium-induced
      bronchoconstriction in which to evaluate the mechanism of action of this airway
      response. We evaluated nine inbred strains of mice for the development of
      atracurium-induced bronchoconstriction. The maximal difference in the magnitude
      of the airway response to atracurium noted between the highly responsive DBA/2
      mice and the minimally responsive SJL mice was greater than 20-fold. This
      phenotype appears to reflect an intrinsic difference in the lungs of these
      animals because the extent of neuromuscular blockade was not significantly
      different in DBA/2 and SJL mice. Atracurium-induced airway hyperresponsiveness in
      DBA/2 mice was eliminated in a dose-dependent manner by pretreatment with
      atropine or pancuronium. These data are consistent with a postganglionic vagal
      efferent mechanism which produces a differential pulmonary response to this
      neuromuscular blocker. A genetic predisposition to atracurium-induced
      bronchoconstriction appears to exist in certain inbred strains of mice. Thus, a
      mouse model may be useful for mapping the gene(s) that control this trait and for
      suggesting responsible candidate genes. Our results suggest that the inbred
      laboratory mouse will be useful to study the mechanism by which atracurium
      produces bronchoconstriction.

PMID- 7735613
TI  - Hydrogen peroxide-scavenging properties of sheep airway mucus.
AB  - Reactive oxygen species released from luminal phagocytes in the airway can
      potentially injure the airway epithelium. Naturally occurring oxygen radical
      scavengers must therefore exist to protect the epithelium. This study was
      designed to determine whether the high-molecular-weight fraction of normal sheep
      tracheal mucus has hydrogen peroxide (H2O2)-scavenging activity. Lyophilized
      mucus from 10 sheep was reconstituted in phosphate-buffered saline (PBS) or Krebs
      Henseleit buffer. H2O2 was added to these mucus samples to a final concentration
      of 15 microM, and the level of H2O2 remaining was measured over a 10 min period.
      From a zero-time level of 17 +/- 1.8 microM (mean +/- SD), the H2O2 concentration
      fell within 10 min to 8 +/- 1.7 microM in 0.05%; to 3.9 +/- 2.2 microM in 0.1%;
      to 2.6 +/- 2.4 microM in 0.2%; and to 1.2 +/- 1.5 microM in 0.4% mucus
      reconstituted in PBS. The results obtained in Krebs-Henseleit buffer were
      similar. The disappearance of H2O2 was not due to the transformation into
      hydroxyl radicals. Heat and acid denaturation and cleavage of carbohydrate-free
      peptides from glycoproteins by pronase E treatment abolished the scavenging
      potential. Fractionation of 0.4% mucus samples according to molecular weight by
      gel filtration revealed that only one fraction with proteins of M(r) > 110 kD
      contained the active scavenger. Polyacrylamide gel electrophoresis and lectin
      blotting with Ulex europaeus I (UEAI) showed that both the whole mucus and the
      actively scavenging gel filtration fraction contained a glycoprotein that
      comigrated with a 205 kD molecular weight marker.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7735614
TI  - Subpopulations of alveolar macrophages in smokers and nonsmokers: relation to the
      expression of CD11/CD18 molecules and superoxide anion production.
AB  - We were previously able to show that the number of alveolar macrophages (AM)
      expressing CD11/CD18 molecules is increased in smokers compared with nonsmokers
      and related to the superoxide anion (O2-) production of these cells. Since it has
      been demonstrated that AM are a heterogeneous cell population that can be
      separated by density, we performed this study to investigate the expression of
      CD11/CD18 molecules and O2- production in relation to cell density of AM from
      smokers and nonsmokers. AM were obtained by bronchoalveolar lavage (BAL) from
      smokers (n = 32) and nonsmokers (n = 20). Subpopulations were isolated using
      discontinuous Percoll density-gradient centrifugation with four densities
      (fraction 1: 1.030; fraction 2: 1.040; fraction 3: 1.050; and fraction 4: 1.070
      g/ml). Expression of CD11/CD18 on freshly isolated cells and on AM before and
      after density centrifugation was studied using peroxidase-antiperoxidase
      staining. The contribution of AM subpopulations to O2- production in smokers was
      determined by monitoring the reduction of ferricytochrome C to ferrocytochrome C.
      We obtained 0.92 +/- 0.1 x 10(5) AM/ml BAL in nonsmokers and 2.4 +/- 0.3 x 10(5)
      AM/ml in smokers. Recovery after density centrifugation was > or = 72%. The
      absolute number of AM in smokers was significantly increased in fractions 3 and 4
      (median 4.37 x 10(6) and 2.05 x 10(6), respectively) compared with nonsmokers
      (median 1.26 x 10(6) and 0.7 x 10(6), respectively) (p < 0.05). In both smokers
      and nonsmokers, fractions 3 and 4 showed a comparable increase in the percentage
      of CD11/CD18-positive AM compared with fractions 1 and 2.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7735615
TI  - Ciliary defects in healthy subjects, bronchiectasis, and primary ciliary
      dyskinesia.
AB  - To develop criteria to aid in the diagnosis of primary ciliary dyskinesia (PCD)
      we analyzed quantitatively the incidence and the range of ciliary ultrastructural
      abnormalities in healthy subjects and in patients with respiratory tract disease.
      The beat frequency and ultrastructure of nasal respiratory tract cilia, including
      ciliary orientation, were measured in 62 healthy subjects (31 nonsmokers, 20
      exsmokers, and 11 smokers), ranging in age from 1 to 76 yr, and in 51 patients
      with respiratory tract disease. In healthy subjects, ciliary beat frequency (CBF)
      ranged between 9.6 and 15.3 Hz, the incidence of microtubule defects varied
      between 0 to 9%, the mean number of inner dynein arms per cilium ranged from 3.0
      to 7.1, and the mean number of outer dynein arms per cilium ranged from 7.4 to
      9.0. The deviation of cilia in healthy subjects varied between 8 and 29 degrees.
      By comparing the data for ciliary defects in healthy subjects with the data
      obtained from patients with respiratory disease, we identified two patient
      groups: patients with PCD (n = 31) and patients with respiratory tract disease
      not due to PCD. For comparison with the PCD patients, a group of 20 patients with
      bronchiectasis was selected and analyzed. Patients with PCD had significantly
      lower CBF (p < 0.001), significantly higher incidences of peripheral and central
      tubule defects (p < 0.01), and greater ciliary disorientation (p < 0.005). There
      was a strong correlation between CBF and the number of outer dynein arm numbers,
      but not with inner dynein arm numbers, suggesting that inner and outer dynein
      arms may play different functional roles in producing ciliary motility.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7735616
TI  - Mechanical ventilation-induced pulmonary edema. Interaction with previous lung
      alterations.
AB  - The risk of lung injury due to alveolar overdistension during mechanical
      ventilation has been clearly delineated in healthy animals with intact lungs. In
      contrast, the effect of high-volume ventilation (HV) on previously injured lungs
      is less well documented: whether HV would simply add its own deleterious effects
      or act synergistically with previous injury has not been addressed. We compared
      the effect of 7 ml/kg body weight tidal volume mechanical ventilation for 2 min
      with that of 25 (HV25), 33(HV33), and 45(HV45) ml/kg body weight HV in
      anesthetized rats previously exposed or not exposed to alpha-naphthylthiourea
      (ANTU). ANTU alone produced moderate permeability edema with significant
      increases in extravascular lung water (Qwl), dry lung weight (DLW), and albumin
      distribution space in lungs (ASp). HV alone resulted in a permeability edema in
      which severity was dependent on the magnitude of the tidal volume. The effects of
      HV25 and HV33 and those of ANTU were only additive, as indicated by the absence
      of any significant two-factor (ANTU-HV) interaction by analysis of variance
      (ANOVA). In contrast, HV45 after ANTU produced significantly greater increases in
      Qwl, DLW, and ASp than expected from the sum of the effects of either insult
      alone. Two-way ANOVA disclosed two-factor interactions with p values < 0.001, <
      0.02, and < 0.01 for Qwl, DLW, and ASp, respectively, indicating synergistic
      adverse effects on pulmonary edema.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735617
TI  - A morphologic study of lung secretory leukoprotease inhibitor in pneumonia.
AB  - The present study was undertaken to determine the localization of cells laden
      with secretory leukoprotease inhibitor (SLPI) in bronchial/bronchiolar epithelium
      (B/Br-E) by histochemical techniques to see whether SLPI production occurs in
      conjunction with pathologic bronchopneumonia. Ten lung were obtained at autopsy
      from patients between 63 and 100 yr of age, including six with pathologic
      pneumonia and four without pneumonia. SLPI-laden cells in the B/Br-E corresponded
      mostly to goblet cells with apparent hyperplasia. A morphometric study performed
      on the B/Br-E indicated that the percentage of SLPI-laden cells was significantly
      correlated with the percentage of mucus-containing cells (r = 0.72, p < 0.001).
      This trend was similar in the bronchi (r = 0.60, p < 0.05) and in the bronchioles
      (r = 0.90, p < 0.01). The increased percentage of mucus and SLPI-laden cells in
      the B/Br-E was closely correlated with acute inflammatory changes in the adjacent
      alveoli, particularly in bronchi rather than in bronchioles. From these
      observations we conclude that the number of SLPI-laden cells in the airways
      increases in correlation with goblet cell hyperplasia. In addition, these
      morphologic changes are associated with the existence of acute inflammatory cell
      infiltration in the alveolar area.

PMID- 7735618
TI  - Effect of erythromycin on endotoxin-induced microvascular leakage in the rat
      trachea and lungs.
AB  - To determine whether the macrolide antibiotic erythromycin prevents microvascular
      leakage produced by lipopolysaccharide (LPS), we studied tracheae and lungs of
      pathogen-free rats. Tracheal vascular permeability and neutrophil recruitment
      were assessed by the percent area occupied by Monastral blue-labeled blood
      vessels and by myeloperoxidase-containing granulocytes, respectively, in tracheal
      whole mounts. Pulmonary microvascular leakage was evaluated by lung wet-to-dry
      (W/D) weight ratio. Inhalation of Escherichia coli LPS (5 mg/kg) caused time
      dependent increases in tracheal vascular permeability, neutrophil influx, and
      lung W/D ratio. These responses were inhibited by pretreatment with oral
      erythromycin, but not by ampicillin or cefaclor, in a dose-dependent manner:
      erythromycin at 10 mg/kg daily for 1 wk reduced the area density of Monastral
      blue-labeled vessels from 6.7 +/- 1.2 to 1.4 +/- 0.3% (p < 0.01), the number of
      neutrophils (from 365 +/- 51 to 149 +/- 30 cells/mm2, p < 0.01), and lung W/D
      weight ratio (from 6.76 +/- 0.30 to 5.39 +/- 0.21, p < 0.01). This inhibitory
      effect of erythromycin was abolished by depletion of circulating neutrophils with
      cyclophosphamide. These results suggest that LPS causes acute lung injury,
      microvascular leakage, and neutrophil recruitment in the trachea, and that
      erythromycin protects against these changes, probably by acting on neutrophils.

PMID- 7735619
TI  - Distribution of functional adrenergic receptor subtypes in the microcirculation
      of rat trachea.
AB  - Although blood flow to the pulmonary airways is known to be largely under
      sympathetic control, virtually nothing is known about adrenergic regulation of
      vascular segments within the airway microcirculation. To evaluate the
      distribution of functional adrenergic receptor subtypes in the microvessels of
      the large airways, the change in diameter of adventitial vessels in rat trachea
      was measured following suffusion with selective and nonselective receptor
      agonists and antagonists. Microvessels were viewed with a video microscope, and
      vessel diameters were measured using video calipers. Arterioles (11.0 to 40.0
      microns, n = 32), small postcapillary venules (11.0 to 26.0 microns, n = 16),
      medium venules (28.0 to 59.5 microns, n = 40), and large collecting venules (61.0
      to 99.0 microns, n = 42) were distinguished. Similar sensitivities to
      norepinephrine (NE), a mixed alpha 1 and alpha 2 agonist, were observed in
      arterioles and medium venules with EC50 (agonist concentration needed to produce
      50% of the maximal response) for contraction of 2.4 x 10(-7) and 3.3 x 10(-7) M,
      respectively. Large venules (EC50 of 1.6 x 10(-6) M) were significantly (p <
      0.05) less sensitive than arterioles to NE. In the presence of propranolol, a
      beta receptor antagonist, the EC50 values for NE were not different between the
      three vessel groups, although the response to low doses of NE was significantly
      increased in arterioles. When vessels were treated with propranolol and
      phenylephrine, a selective alpha 1 agonist, arterioles (EC50 of 4.1 x 10(-7) M)
      were significantly more sensitive than large venules (EC50 of 4.9 x 10(-6)
      M).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735620
TI  - Interleukin-8. Differential expression in lone fibrosing alveolitis and systemic
      sclerosis.
AB  - Fibrosing alveolitis may occur alone (CFA) or in association with systemic
      sclerosis (FASSc). FASSc was recently shown to have a prognostic advantage over
      CFA. Because interleukin-8 (IL-8) is likely to be a major determinant of
      neutrophil alveolitis, we evaluated IL-8 expression in patients with CFA and
      FASSc and compared it with that in normal individuals and sarcoidosis and
      systemic sclerosis patients without pulmonary involvement (SSc no FA). IL-8
      protein in bronchoalveolar lavage fluid (BALF) was assessed by immunoassay, and
      IL-8 mRNA expression was assessed using Northern analysis and reverse
      transcription-polymerase chain reaction (RT-PCR) and in situ hybridization of
      lung parenchyma. Compared with normal subjects, IL-8 concentration was
      significantly greater in both CFA (p < 0.001) and FASSc groups (p < 0.05) but no
      different in sarcoidosis. The IL-8 concentration in CFA was higher than in FASSc
      (p < 0.01) and was related to BAL % neutrophils (rs = 0.48, p < 0.01). IL-8 mRNA
      expression evaluated by Northern analysis was seen only in patients with CFA and
      FASSc and was related to BAL % neutrophils (rs = 0.63, p < 0.01). We suggest that
      IL-8 is a key factor in the pathogenesis of fibrosing alveolitis and that the
      poorer prognosis of CFA compared with FASSc is related to higher levels of IL-8
      within the lower respiratory tract.

PMID- 7735621
TI  - Human alveolar macrophages produce predominantly the 35-kD pro-forms of
      interleukin-1 alpha and interleukin-1 beta when stimulated with
      lipopolysaccharide.
AB  - Alveolar macrophages (AM) play a key role in local immunoregulation. The
      objective of these studies was to compare the production of the pro- and mature
      forms of both interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta)
      by AM from nine nonsmoking control subjects, six asymptomatic smokers, and nine
      patients with interstitial lung disease (ILD). IL-1 alpha and IL-1 beta steady
      state mRNA levels in AM cultured over 20 h were determined using specific cDNA
      probes. IL-1 alpha, 35-kD pro-IL-1 beta, and 17-kD mature IL-1 beta protein
      levels in cell lysates and supernatants were determined by individual specific
      ELISAs. Before culture, the isolated AM contained no IL-1 alpha or IL-1 beta
      mRNA. AM from nonsmoking control subjects and asymptomatic smokers produced
      comparable levels of IL-1 alpha protein, 5.01 +/- 1.02 ng/ml and 4.54 +/- 1.07
      ng/ml, respectively, only after stimulation with lipopolysaccharide (LPS) and not
      with granulocyte-macrophage colony-stimulating factor (GM-CSF). The majority of
      the IL-1 alpha was present in the cell lysates as 35-kD pro-IL-1 alpha, as
      determined by Western blot analysis. AM from patients with ILD produced higher
      levels of LPS-induced cell-associated IL-1 alpha protein (9.78 +/- 1.80 ng/ml, p
      = 0.031). LPS-induced IL-1 beta production by AM from nonsmoking control subjects
      (5.22 +/- 1.89 ng/ml) and asymptomatic smokers (4.39 +/- 0.66 ng/ml) was
      equivalent to total IL-1 alpha protein production.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7735622
TI  - The effect of inhalation of platelet-activating factor on the pulmonary clearance
      of 99mTc-DTPA aerosol.
AB  - Platelet-activating factor (PAF) is a short-acting, lipid-soluble autocoid,
      inhalation of which causes an immediate pulmonary vascular sequestration of
      granulocytes and a peripheral neutropenia. We investigated the effect of PAF
      inhalation on the pulmonary clearance rate of inhaled 99mTc-DTPA in order to test
      the hypothesis that the pulmonary sequestration of granulocytes results in acute
      lung injury. In nine normal nonsmoking adults, the rate of clearance of DTPA,
      corrected for background activity, was 1.5 (SD 0.7) %/min over the first 10 min
      after inhalation. Inhalation of 4.8 micrograms PAF abruptly increased the
      clearance rate to a mean value of 2.3 (1.4) %/min (p < 0.05). No increase in
      clearance was observed in four nonsmoking subjects who inhaled vehicle only. The
      mean overall increase after PAF was 87% of the baseline clearance, significantly
      different (p < 0.05) from the corresponding change in the control group, which
      was -17%. After PAF, the clearance rate returned to baseline values within 10 min
      in all subjects. In all subjects who inhaled PAF, but in none who inhaled
      vehicle, there was an immediate neutropenia of 51 (SD 25) % of the baseline value
      (p < 0.01). This neutropenia persisted longer than the corresponding accelerated
      DTPA clearance and was still 74 (36) % of the baseline value at 10 min.
      Furthermore, there was no correlation between the increase in DTPA clearance
      induced by PAF inhalation and the decrease in peripheral blood granulocyte count.
      We conclude that PAF inhalation results in an increase in pulmonary DTPA
      clearance, probably not mediated by pulmonary vascular granulocyte sequestration.

PMID- 7735623
TI  - Asthma in Jemez Pueblo schoolchildren.
AB  - Asthma, a major chronic health problem of children, has received little
      investigation in Native Americans. We conducted a survey of asthma in children of
      Jemez Pueblo, Jemez, New Mexico, in response to concerns of the community and
      health care providers about the frequency of asthma. In collaboration with Jemez
      Pueblo, we developed a standardized questionnaire and administered it to parents
      of 318 children aged 3 to 13 years. Parents reported that 12.3% had been
      diagnosed as having asthma or reactive airway disease by a physician or other
      health care practitioner. Asthma was reported as still active at the time of the
      interview for 55% of those subjects. The study showed that asthma was not
      uncommon among the Jemez Pueblo children and, in fact, was more common than in
      recent nationwide surveys.

PMID- 7735624
TI  - Increased interleukin-1 and interleukin-6 serum concentrations in severe primary
      pulmonary hypertension.
AB  - Primary pulmonary hypertension (PPH) is characterized by the proliferation of
      smooth-muscle cells, fibroblasts, and endothelial cells in the walls of small
      pulmonary arteries. In order to evaluate a role for proinflammatory cytokines in
      this process, we studied the concentration of interleukin-1 beta (IL-1 beta), IL
      6, and tumor necrosis factor-alpha (TNF alpha) in the serum of 29 patients with
      severe PPH referred to our center for lung transplantation. Results were compared
      with those obtained in 15 normal controls and nine patients with pulmonary
      hypertension secondary to chronic obstructive pulmonary disease (COPD-PH). TNF
      alpha serum levels were within the normal range in each group. This contrasted
      with increased IL-1 beta serum levels in severe PPH (118 +/- 36 pg/ml, mean +/-
      SEM) as compared with controls (3 +/- 1 pg/ml, p < 0.001) or COPD-PH patients (3
      +/- 1 pg/ml, p < 0.001). IL-6 serum concentrations were also higher in severe PPH
      (66 +/- 20 pg/ml) than in controls (14 +/- 6 pg/ml, p < 0.01). This study
      demonstrates increased serum levels of IL-1 beta and IL-6 in severe PPH, and
      suggests a role for proinflammatory cytokines in PPH.

PMID- 7735625
TI  - Ramp abuse. A novel form of patient noncompliance to administration of nasal
      continuous positive airway pressure for treatment of obstructive sleep apnea.
AB  - Administration of nasal continuous positive airway pressure (NCPAP) is the
      treatment of choice for most patients with obstructive sleep apnea. Many patients
      experience side effects with NCPAP use, and the compliance rate is reported to
      vary between 46-89%. The ramp is a device found on many NCPAP machines that
      resets the pressure to 3 cm H2O and then slowly increases the pressure to the
      prescribed pressure over a period of up to 45 min. The ramp allows patients time
      to fall asleep before the higher and likely more uncomfortable prescribed
      pressure is administered. We present a case in which a patient's repeated remote
      controlled activation of this ramping feature severely limited effective therapy
      even when the NCPAP mask was properly in place, the machine was on, and the
      patient was breathing nasally.

PMID- 7735626
TI  - Childhood- versus adult-onset asthma.

PMID- 7735627
TI  - Viral infections and the development of asthma.
AB  - The possible role of viral infections in the inception of asthma has been the
      matter of considerable debate. Older data suggested that viral respiratory
      infections occurring during early life could alter the lungs and the immune
      system, thus starting the process leading to allergic sensitization and
      persistent bronchial responsiveness. More recent studies suggest that infants who
      wheeze belong to two distinct groups, which at present can only be differentiated
      by the evolution of their illness. Most of these infants have a transitory
      tendency to wheeze during viral infections, and their lung function shortly after
      birth is significantly lower than that of infants who will not wheeze during
      similar infections. Most of these children become symptom-free during the
      preschool years, and their condition is not associated with higher serum IgE
      levels. A smaller group of children who wheeze as infants will still have
      wheezing episodes during the early school years. The factors that determine which
      infants will become persistent wheezers are not well understood, but viral
      infections per se are likely to play a minor role, if any. Early sensitization to
      aeroallergens in subjects genetically predisposed to having high serum IgE levels
      seems to be the main risk factor for this condition.

PMID- 7735628
TI  - Do lower respiratory tract infections in early childhood cause chronic
      obstructive pulmonary disease?
AB  - The hypothesis that lower respiratory tract infections (LRTI) in early childhood
      lead to chronic obstructive pulmonary disease (COPD) in late adult life has been
      difficult to test. However, a unique opportunity arose when records were
      discovered in the counties of Hertfordshire and Derbyshire, England, that
      contained information about childhood LRTI recorded 60 to 70 years ago. The lung
      function of some men still living in these counties was examined. In
      Hertfordshire men, bronchitis or pneumonia in infancy was associated with reduced
      mean FEV1, adjusted for age and height. In Derbyshire men, pneumonia before 2 yr
      of age was associated with a large and highly significant reduction in mean FEV1,
      adjusted for age and height. These findings were independent of smoking and
      social class. These data support a causal relationship between LRTI in early life
      and subsequent COPD.

PMID- 7735629
TI  - Epidemiology of respiratory viruses in persons with and without asthma and COPD.
AB  - The occurrence of respiratory viruses in persons with asthma and COPD must be
      viewed against the behavior of the viruses in persons without these conditions.
      There are multiple agents involved, and reinfections with the same virus are
      frequent. Infections and illnesses generally decrease in frequency with
      increasing age. Thus, it can be expected that infections among children, with or
      without asthma, will be more frequent than among adults in general. Evaluation of
      studies of viral activity in persons with asthma and COPD should differentiate
      between increased susceptibility and production of exacerbations. The latter may
      simply indicate the potential for greater severity, but not a higher frequency,
      of infections. Whatever viruses are circulating at a particular time can produce
      exacerbations; the studies are most conclusive for asthma in children, probably
      because infections in general are more common in this age group. Data also
      suggest increased susceptibility, although results are less clear than for
      exacerbations. Therefore, persons with chronic respiratory diseases should be
      considered a risk group for current and developmental vaccines and antiviral
      medications.

PMID- 7735630
TI  - Mechanisms of airway narrowing and hyperresponsiveness in viral respiratory tract
      infections.
AB  - Viral respiratory tract infections are associated with an acute increase in
      airway responsiveness in normal subjects and patients with asthma. Airway
      responsiveness is also increased at least transiently in animals during acute
      viral infections. In this article, we discuss possible mechanisms whereby viral
      infections can increase airway responsiveness, emphasizing the effects of viral
      induced airway epithelial damage during acute lytic infection and the mechanical
      consequences of airway inflammation and edema, both internal and external to the
      smooth muscle layer. We also describe possible mechanisms by which acute lytic
      viral infections could induce chronic sequelae in atopic individuals and
      contribute to the development of persistence of asthma. Finally, results of
      recent studies from our laboratory that document adenoviral genome in lungs of
      patients with chronic obstructive pulmonary disease (COPD) and long-term
      persistence of respiratory syncytial viral genome and protein in an animal model
      are discussed in terms of the possible role of latent and persistent viral
      infections in the pathogenesis of asthma and COPD.

PMID- 7735631
TI  - Virus-induced airway hyperresponsiveness. Role of inflammatory cells and
      mediators.
AB  - Viral respiratory infections induce airway hyperresponsiveness in asthmatic
      patients, in healthy persons, and in a number of animal species. In asthmatics
      the degree of airway hyperresponsiveness is associated with the severity of
      exacerbations. The respiratory tract of an asthmatic is inflamed, and these
      inflammatory cells might be involved in modulating airway responsiveness. In
      contrast, no data are available on the role of bronchoalveolar cells in the
      airways of "healthy" persons or asthmatic patients suffering a respiratory tract
      infection. Because of the lack of information on this issue, the present review
      has been written. A number of animal studies have now been performed suggesting
      the involvement of inflammatory cells during a viral respiratory infection. The
      changes in number and activity of bronchoalveolar cells after a viral infection
      have been compared with changes in airway morphology and the development of
      airway hyperresponsiveness. Based on these data we suggested, the following
      hypothesis: Viruses damage the epithelial layer of the respiratory tract and
      activate bronchoalveolar cells. Subsequently, a number of mediators are released
      that can stimulate metachromatic cells, which in turn release products that
      increase vascular permeability and attract inflammatory cells that might cause
      additional epithelial damage. Finally, the released mediators and the morphologic
      changes together results in airway obstruction and the development of
      hyperresponsiveness.

PMID- 7735632
TI  - Viral infections in humans.
AB  - Viral respiratory infections can increase asthma symptoms in many patients.
      Although the mechanisms of these effects are not fully established, there is
      evidence that respiratory viruses can promote some components of allergic
      inflammation. In this regard, there is evidence that rhinovirus respiratory
      infections can lead to the development of late allergic reactions to inhaled
      allergen. This change in response to inhaled allergen supports the possibility
      that some respiratory infection will promote bronchial inflammation and may be a
      factor for increased wheezing with respiratory infection.

PMID- 7735633
TI  - Sequelae of respiratory syncytial virus infections. A role for intervention
      studies.
AB  - The association between respiratory syncytial virus (RSV) infections in infancy
      and respiratory abnormalities later in life has been attributed both to a direct
      effect of the infection itself and to an inherent susceptibility. Observational
      studies do not allow a rigorous test of these hypotheses. Respiratory syncytial
      virus infection is universal in the first years of life and no uninfected control
      group exists. Randomized, controlled trials using new prophylactic agents such as
      vaccines or specific therapeutic agents will provide a powerful test of the
      relationship between RSV infection and long-term respiratory sequelae.

PMID- 7735634
TI  - Sense and nonsense of influenza vaccination in asthma and chronic obstructive
      pulmonary disease.
AB  - Although influenza is generally seen as an important cause of excess mortality in
      patients with asthma or chronic obstructive pulmonary disease (COPD), this
      mortality is nearly exclusively present in patients over the age of 60. Morbidity
      in patients with asthma or COPD is related to respiratory infections, including
      influenza. Vaccination against influenza has proven to be effective in nursing
      home populations, decreasing both mortality and morbidity during epidemics of
      influenza A. In younger patients with asthma or COPD, however, the effect of
      vaccination is more ambiguous. Exacerbation of respiratory disease is not due to
      influenza vaccination (except in allergy to chicken protein), from which we can
      conclude that influenza vaccination is a safe method to prevent a potentially
      serious respiratory infection in patients with asthma or COPD.

PMID- 7735635
TI  - Bradykinin-induced contraction of human peripheral airways mediated by both
      bradykinin B2 and thromboxane prostanoid receptors.

PMID- 7735636
TI  - Fish consumption may limit the damage of smoking on the lung.

PMID- 7735637
TI  - Nitric oxide and VIP as co-transmitters of neurogenic relaxation of human
      airways.

PMID- 7735638
TI  - An empirical technique to compensate for melanin when monitoring skin
      microcirculation using reflectance spectrophotometry.
AB  - Errors can occur in measuring blood content and oxygenation in subjects with
      significant skin pigmentation using reflectance spectrophotometry. The melanin in
      the epidermis not only reduces the amount of back-scattered light, but also has a
      characteristic absorption spectrum that varies between individuals. Skin color is
      primarily influenced by the concentration of melanin, blood content and
      oxygenation in the superficial microvasculature. A three-step process was
      developed empirically to accommodate the effect of melanin in the absorption
      spectrum of skin. A melanin index was developed and applied for each individual
      tested. Spectral components attributable specifically to melanin were subtracted
      from the measured spectrum, and its amplitude was normalized. This technique was
      tested with 26 able-bodied subjects with different levels of skin pigmentation.
      The melanin-compensated spectra from pigmented and caucasian skin were
      indistinguishable and no correlation was found between calculated values for
      indices of blood content and oxygenation, and melanin index.

PMID- 7735639
TI  - An intramedullary aligned bone cutting jig for elbow replacement.
AB  - One of the main post operative complications of total elbow replacement has been
      dislocation and fracture of the olecranon. This has been associated with
      rotational malalignment of the bone cuts of the proximal ulna caused by the
      current free hand cutting method. This paper presents an intramedullary aligned
      bone cutting jig which gives rotational location on the ulna for the bone cuts,
      without notching the olecranon.

PMID- 7735640
TI  - A multi-sample denaturation temperature tester for collagenous biomaterials.
AB  - The temperature at which collagen denatures from a triple helix to a random coil
      structure is a useful measure of the degree of crosslinking. A new multi-sample
      denaturation temperature tester (DTT) has been constructed for rapid
      determination of the collagen denaturation temperature of natural tissues and
      collagenous biomaterials. To validate the system, the denaturation temperatures
      measured for the DTT are compared with results from differential scanning
      calorimetry (DSC). Data are presented for bovine pericardium in three states with
      denaturation temperatures ranging from 68 to 85 degrees C: fresh, or crosslinked
      with glutaraldehyde or the epoxide reagent Denacol EX-512 poly (glycidyl ether).
      Denaturation temperatures measured by DTT were not significantly different from
      those measured by differential scanning calorimetry (DSC); however, DSC onset
      systematically occurred at a slightly lower temperature than that measured by
      DTT. This result, seen only for fresh tissue is in agreement with earlier
      experiments using hydrothermal isometric tension (HIT) testing. By contrast, DTT
      and DSC onset were identical for the exogenously crosslinked materials. Since the
      measured transition temperature was independent of initial load, this variable
      may be chosen to yield sharper force-temperature transitions with a given sample
      geometry. This instrument allows accurate assessment of collagen denaturation
      temperatures for multiple samples in a fraction of the time required by other
      methods.

PMID- 7735641
TI  - Four channel foetal ECG data collection system.
AB  - Recently there has been an increased interest in the development of improved
      techniques for the diagnosis of foetal distress during labour. Many of the
      techniques have been based on extracting extra information from the foetal ECG
      obtained from a scalp electrode. To fully develop and test the prototypes of
      these systems requires recorded data from patients. However due to the poor level
      of prediction of these cases at present, it is very difficult to collect the data
      using simple single channel data collection systems. The system described here
      will automatically collect and document data from up to four deliveries at the
      same time and does not add to the work load of the clinical staff.

PMID- 7735642
TI  - Three-dimensional finite element modelling of non-invasively assessed trabecular
      bone structures.
AB  - The three-dimensional microstructure of cancellous bone seems to be one of the
      key factors in the prediction of mechanical bone properties like bone strength or
      bone stiffness. In this paper trabecular bone structure was assessed
      nondestructively by means of high-resolution computed tomography (CT) with a
      spatial resolution of 250 microns. Mineralized bone was separated from bone
      marrow and muscle tissue with the help of a three-dimensional segmentation
      algorithm based on the analysis of directional derivatives. From the three
      dimensional stack of CT slices a subvolume comparable in size (3.6 x 3.4 x 3.4
      mm3) to standard histologic bone sections was selected. We refer to this
      subvolume as non-invasive bone biopsy. A new automated mesh generator was
      developed to create a three-dimensional finite element model of the non-invasive
      bone biopsy. Four-noded tetrahedron solid elements were used to guarantee a
      smooth surface representation. The aim of the presented work was to demonstrate
      the potential of high-resolution CT imaging in the prediction of the anisotropic
      material properties of cancellous bone. Preliminary results of the 3D finite
      element stress analysis are very promising. The predicted value of the apparent
      Young's modulus (564 MPa) is within the range reported for uniaxial compression
      testings of cancellous bone specimens.

PMID- 7735643
TI  - A mathematical model of flow through the terminal lymphatics.
AB  - Proper understanding of the mechanisms of fluid absorption and flow through the
      terminal lymphatics is essential for the control of several pathological
      conditions such as edema, bedsores and cancer. A mathematical model of the
      terminal lymphatics was developed using the principles of mechanics. Computer
      simulation results substantiate the hypothesis that fluid absorption and flow
      through the terminal lymphatics occur due to suction mechanisms of the adjacent
      contractile lymphatic segments and due to periodic fluctuations in the
      interstitial fluid pressure. In addition, the results suggested that increasing
      the length of a terminal lymphatic vessel beyond a certain limit does not cause
      further increase in fluid flow into the terminal lymphatic.

PMID- 7735644
TI  - A regression model of ultrasound reflectivity from normal myocardium.
AB  - In this paper the potentialities of back-scattered ultrasound to detect changes
      in transmural myocardial wall structure have been assessed by using a second
      order regression model of integrated back-scatter. The model was tested through
      simulation studies and experimental measurements. The experimental results prove
      the proposed model attractive to detect physiological transmural changes in
      myofibre orientation from epicardial to endocardial left ventricular wall.

PMID- 7735645
TI  - Dynamic performance model of an isometric muscle-joint unit.
AB  - The dynamic performance model of the medial gastrocnemius muscle of the cat was
      determined when generating isometric force at its tendon and when transmitting
      that force across the joint. The frequency response model of the muscle and of
      the muscle-joint was developed by fitting the experimentally obtained gain and
      phase Bode plots with a best fit linear second order system determined by
      recursive least squares. It was shown that the muscle could be represented with
      double poles at 2.3 Hz and a time delay of 16 ms whereas the muscle-joint was
      represented with an additional pole at 1.8 Hz, a zero at 3.8 Hz and 16 ms time
      delay. The harmonic distortion was less than 5% for sinusoidal force output in
      the frequency range of 0.4-4 Hz, and a force range of 20-80% of the maximal
      justifying a linear system model. The model is useful in the design of a
      neuromuscular prosthesis, using electrical stimulation of the muscle nerves, as a
      rehabilitation procedure for paralysed patients due to spinal cord injury.

PMID- 7735646
TI  - Real time microcontroller implementation of an adaptive myoelectric filter.
AB  - This paper describes a real time digital adaptive filter for processing
      myoelectric signals. The filter time constant is automatically selected by the
      adaptation algorithm, giving a significant improvement over linear filters for
      estimating the muscle force and controlling a prosthetic device. Interference
      from mains sources often produces problems for myoelectric processing, and so 50
      Hz and all harmonic frequencies are reduced by an averaging filter and
      differential process. This makes practical electrode placement and contact less
      critical and time consuming. An economic real time implementation is essential
      for a prosthetic controller, and this is achieved using an Intel 80C196KC
      microcontroller.

PMID- 7735647
TI  - An examination of procedures for determining body segment attitude and position
      from noisy biomechanical data.
AB  - For the kinematic analysis of movement it is necessary to determine the position
      and attitude of rigid bodies in some specified reference frame. In biomechanics,
      these rigid bodies are usually segments of the human body, and the position of a
      distal segment is normally defined relative to a proximal segment. It was the
      purpose of this study to compare the accuracy of three approaches for the
      determination of the position and attitude of rigid bodies under four different
      noise conditions which were designed to model the conditions found in
      biomechanics studies. One technique investigated assumes the data are error free;
      another uses matrix algebra and employs matrix perturbation theory; and the third
      is a least-squares procedure. The evaluation was performed using a computer
      simulation which attempted to model 'typical' experimental conditions found in
      biomechanical studies. The attitude of the distal rigid body was defined using
      helical angles, with these angles being generated using a random number
      generator. All three techniques were assessed by their ability to predict a set
      of known helical angles and position vectors under different noise conditions.
      The study demonstrated that the least-squares technique was the most accurate for
      determining the attitude matrix and position vector for the cases investigated.
      None of the techniques investigated could allow for anisotropic noise conditions,
      yet anisotropic noise conditions are often obtained when using measurement
      procedures common in biomechanics. The study also highlighted the need to low
      pass filter data prior to the computation of the position and attitude of rigid
      bodies.

PMID- 7735648
TI  - Deceleration vs. acceleration: a haemodynamic parameter in the assessment of
      vascular reactivity. A preliminary study.
AB  - The parameter deceleration vs. acceleration (dc/ac) as derived from the
      instantaneous peak velocity is obtained by dividing the descending and ascending
      slopes of plotted velocity curves. Blood velocities were recorded with a
      specially designed continuous-wave ultrasonic Doppler unit which provides: the
      instantaneous peak velocity, the instantaneous mean velocity, the acceleration,
      and an indication of volume flow. A physical meaning to the dc/ac parameter is
      given through an analysis, based on an electrical model, of a small portion of an
      artery. This gives a simple relationship which only takes account of the assumed
      vascular resistances. Measurements were performed in 67 male subjects; 39 were
      normotensive control subjects and 28 had established moderate hypertension. In
      both groups there was an increase of dc/ac in passing from the supine to the
      erect position, the increase being more accentuated by hypertension. The
      variation of dc/ac with age was significantly different in both groups. The
      results suggest that this parameter is a sensitive indicator of variations in
      vascular reactivity and as an indicator of structural changes in the arterial
      wall.

PMID- 7735650
TI  - The important role that work-based learning plays in realizing the maximum
      potential of the organization.

PMID- 7735649
TI  - Arrhythmia recognition strategies and hardware decisions for the implantable
      cardioverter-defibrillator--a review.
AB  - The avoidance of inappropriate shocks from the implantable cardioverter
      defibrillator (ICD), together with its need to apply antitachycardia pacing to
      either atria or ventricles, demands considerable sophistication in the design of
      algorithms to interpret electrical or other cardiac signals in real-time. Methods
      based on rate and using single short-gap bipolar leads lack discrimination. Right
      ventricular electrogram morphology algorithms offer improvement but no universal
      algorithm exists; however, for any given patient an optimum algorithm of this
      type might be found. One improvement would be to provide atrial information in
      addition, by employing more than one electrode or a long-gap single bipolar lead.
      Alternatively, transducer signals could be included, once their efficacy and
      reliability have been improved. A different approach would be to use the much
      more sophisticated algorithms at present being tried with surface
      electrocardiograms. Integrated Circuit technology is reaching the point where
      this could be done but the requirement for exceptionally high reliability means
      that special system structures, such as a Memory Intensive Computer Architecture,
      may be required. When decisions on these approaches are to be made, it must also
      be remembered that ICDs will soon be implanted and programmed as a routine rather
      than a highly specialized procedure.

PMID- 7735651
TI  - Exploring patient satisfaction with out-patient services.
AB  - Despite the widespread use of satisfaction surveys to obtain patients' views
      about health services, the validity and relevance of self-completion
      questionnaire surveys has been questioned. This paper reports on an exploratory,
      qualitative investigation into patients' perspectives on satisfaction and
      dissatisfaction with out-patient care. Eighty-one new referrals to two out
      patient clinics were interviewed before and after their first consultation. Of
      this initial sample, 23 were interviewed again at their follow-up appointment and
      a further 10 were interviewed in depth at a location of their choice. The
      features of the service that drew appreciative comments when they were thought to
      be present, and criticism when they were felt to be lacking, were: humanity,
      efficiency, informativeness and continuity of communication. Examples of these
      features are discussed using patients' own words to illustrate their
      perspectives. The study demonstrates that unstructured approaches to service
      evaluation can be employed to develop services which are genuinely listening to
      their users' views.

PMID- 7735652
TI  - The transformation of nurses' work?
AB  - This paper offers a critical discussion of how current and planned changes in the
      labour process within the National Health Service (NHS), with particular
      reference to nursing as an occupational group, are likely to influence the
      industrial relations aspects of nursing management. An attempt is made to apply
      concepts developed within the wider sociology of work, to the reality of latter
      day nurses' experience. In this respect, the question will be addressed: do
      management approaches to the reorganization of work in health care settings
      constitute, or herald, an actual 'transformation' of nurses' work? The approach
      adopted places concern over the introduction of productivity or performance
      related pay, or the implementation of nursing skill-mix reviews within an
      analytic context which considers issues of control over working practices. As
      such, management and unions' responses to NHS Executive calls for increasing
      reorganization of nurses' work and remuneration structures may be illuminated by
      an understanding of this issue of control. This would entail a departure from
      simplistic analyses, focused solely upon narrowly defined efficiency concerns.

PMID- 7735653
TI  - From 19th century nursing reforms to current practice: a selective overview with
      special reference to The Royal London Homoeopathic Hospital (The Royal London
      Homoeopathic Hospital NHS trust from 1993).
AB  - Early nursing reforms in the 19th century are usually associated with
      Nightingale, although later emphasis has been placed on similar movements in the
      Poor Law sector. Extension of nursing influence over decision-making in terms of
      nursing practice and education is charted, using examples from 19th century
      Minutes of hospital committees and more recent experience based mainly on the
      observations made by one of the writers, who had substantial input into steering
      the hospital through the stages prior to achieving National Health Service (NHS)
      Trust status. The significance of nurse executive power following the 1990s NHS
      reforms is highlighted and means of extending the use of this authority are
      explored.

PMID- 7735654
TI  - Computer-based documentation and bedside terminals.
AB  - Rising health care costs and the need for enhancing the quality of clinical care
      are concerns of hospitals throughout the world. Documentation consumes excessive
      amounts of nursing time and directly influences the quality of clinical practice,
      research, administration and education. Recent developments in information
      technology have offered many alternatives to traditional systems of
      documentation. Many hospitals have installed bedside terminals, but only few have
      conducted and published studies regarding their implementation. Most of the
      studies come from the US and report improved quality of care and reduction of
      nursing expenses. All the relevant studies have design, sample and methodological
      problems. There is a need for additional systematic studies to prove the actual
      benefits of the bedside terminals and link them with the outcomes of care. This
      paper intends to review the literature and discuss the installation, use, results
      and future directions of the bedside terminals.

PMID- 7735655
TI  - Job enrichment, work motivation, and job satisfaction in hospital wards: testing
      the job characteristics model.
AB  - This study investigated work motivation and job satisfaction at hospital wards
      with high and low levels of job enrichment. Primary nursing was assumed to
      represent a highly enriched job, whereas functional nursing represented a job
      with a low level of enrichment. Five surgical wards were divided into these two
      categories based on the structured interviews with head nurses. Work motivation
      and job satisfaction among ward personnel were assessed by a questionnaire. The
      ward personnel occupying highly enriched jobs reported significantly higher work
      motivation and satisfaction with the management than the personnel occupying jobs
      with a low level of enrichment.

PMID- 7735656
TI  - AIDS and nursing: psychological and legal issues.

PMID- 7735657
TI  - Studying sexual behaviour.

PMID- 7735658
TI  - Anxiety: one of medicine's blind spots.

PMID- 7735659
TI  - Late paraphrenia.
AB  - Late paraphrenia is one of a group of paranoid disorders arising in the elderly.
      The distinctive clinical and social features of this disorder are highlighted in
      this article together with the possible aetiological causes.

PMID- 7735660
TI  - Organisation of a local revision course for postgraduate examinations.
AB  - Revision courses for postgraduate examinations are usually held at central
      teaching hospitals. The ingredients for these courses, however, are available at
      most local hospitals. This article describes the practicalities of organising a
      successful local revision course for postgraduate examinations.

PMID- 7735661
TI  - Mentally disordered firesetters.
AB  - Research on firesetters suggests that the majority are mentally disordered.
      Schizophrenics are slightly over-represented but most arsonists are characterised
      by abnormal personalities. While motives for firesetting are usually mixed, anger
      and revenge are the commonest. Arsonists tend to be underassertive individuals
      with poor interpersonal skills who are unable to deal effectively with conflict,
      anger and frustration. This perhaps explains their choice of fire as a weapon.

PMID- 7735662
TI  - Peripheral nerve entrapment syndromes: diagnosis and management.
AB  - Symptoms due to nerve entrapment syndromes are a frequent reason for attendance
      at GP, rheumatology and orthopaedic clinics. This article outlines the presenting
      symptoms and signs of some of the more common syndromes and gives guidelines on
      the clinical diagnosis and subsequent management.

PMID- 7735663
TI  - The nephrotic syndrome.
AB  - In children the nephrotic syndrome is an uncommon condition characterised by
      heavy proteinuria, hypoalbuminaemia and oedema. It is most commonly associated
      with minimal glomerular changes and is usually responsive to steroids.

PMID- 7735664
TI  - Complications of transvenous temporary pacemaker insertion.
AB  - The indications for temporary pacemaker insertion are more widely documented than
      the complications. Awareness of the potential complications allows quicker
      diagnosis and may therefore be lifesaving. This article provides a practical
      guide to overcoming the complications of pacemaker insertion.

PMID- 7735665
TI  - Personnel appraisal.
AB  - Personnel appraisal has been neglected in medicine but is now being introduced.
      Individual personnel review is a proven system developed in industry. Goals are
      set, carefully monitored and finally assessed at interview. It can be extremely
      valuable in assessment, and also in the education and encouragement of staff.

PMID- 7735667
TI  - Acute intermittent porphyria: a family study.

PMID- 7735666
TI  - Perioperative haemodynamic monitoring and fluid management--NCEPOD revisited.
      National Confidential Enquiry into Perioperative Deaths.
AB  - This article examines the evidence presented in the National Confidential Enquiry
      into Perioperative Deaths which demonstrates, we believe, that high-risk patients
      may not be receiving appropriate haemodynamic monitoring and fluid management.
      This may contribute to their mortality and merits further investigation.

PMID- 7735668
TI  - Billing rules for medical managers.
AB  - The stages of billing, commencing with the patient referral, are shown in Figure
      1. The process of billing is a core function of a provider unit. Consequently,
      procedures must be in place which allow the system to run effectively and
      smoothly. The process is mostly managed by administrative and financial staff
      supported by increasingly sophisticated information technology. The amount of
      billing is increasing as purchasers steadily shift from block contracts to cost
      and volume and cost per case contracts.

PMID- 7735669
TI  - Management of ventricular arrhythmias.

PMID- 7735670
TI  - Treatment of epiglottitis.

PMID- 7735671
TI  - Paediatric airway management.

PMID- 7735672
TI  - Short-term growth in children.

PMID- 7735673
TI  - Use of nebulised adrenaline in tracheal compression.

PMID- 7735674
TI  - New technique of levator lengthening for the retracted upper eyelid.
AB  - Retraction of the upper eyelid associated with shortening of the levator
      mechanism occurs most commonly in association with Graves' disease but
      occasionally arises as a complication of blepharoplasty or other surgical
      procedures. A new technique of a castellated type aponeurotomy of the levator
      aponeurosis is carried out to lengthen the levator. This procedure appears to
      give a predictable, stable and symmetrical result.

PMID- 7735675
TI  - Cool perfusion solutions for skin flaps: a new mixture of pharmacological agents
      which improves skin flap viability.
AB  - This study tested the hypotheses that perfusion of cooled skin flaps with
      established organ preservation solutions improves their viability and that this
      improvement can be further enhanced by pharmacological manipulation. Rabbit
      epigastric skin flaps were perfused with different solutions before explantation
      and stored at 8 degrees C for 6 days. In the first part of the experiment, flap
      viability was assessed 7 days after reperfusion of the flap via microvascular
      anastomoses. The different solutions were heparinised blood, University of
      Wisconsin solution, two of its modifications, EuroCollins solution and a
      pharmacological mixture containing phosphoenolpyruvate, desferrioxamine,
      nitrendipine, dextran 70 and a platelet-aggregating factor receptor antagonist
      (WEB 2170). In the second part, biochemical parameters of skin were measured at
      various reperfusion times. Adenosine triphosphate (ATP), reduced glutathione
      (GSH), myeloperoxidase (MPO) and tissue water were assayed at 0, 1, and 24 h
      after reperfusion. In addition, plasma thromboxane (TXB2) was measured at 0, 30
      and 60 minutes after reperfusion. The viability of flaps perfused with the
      mixture (81%) was significantly higher than that of any of the other groups (39%
      for controls, 38% for EuroCollins, 13% for UW solution, 27% and 31% for its
      modifications). ATP levels after reperfusion were higher in the mixture group
      than in UW-perfused group. GSH levels in the mixture group were also higher than
      in the UW group, indicating higher level of protection against oxidative stress
      during reperfusion. There were no differences in MPO levels. Thromboxane levels
      associated with UW-perfused flaps were significantly higher than those associated
      with any other perfusion solution. In conclusion, perfusion of a mixture of
      pharmacological agents targeting specific aspects of ischaemia/reperfusion injury
      improved the viability of skin flaps stored in the cold for 6 days, whereas
      standard organ preservation solutions failed to affect significantly skin flap
      survival.

PMID- 7735676
TI  - Use of a rectus abdominis osteomyocutaneous double island flap based on internal
      mammary vessels.
AB  - A very rare condition of osteoma cutis was presented by a patient who required an
      unusual solution to an unusual problem. Multiple surgical procedures were
      performed during the treatment of the disease, thereby prohibiting the use of
      more common regional or distant flaps to achieve successful mandibular
      reconstruction. Microvascular tissue transfer was also not feasible because of
      two previously-failed free flaps and an operative field that was densely
      fibrotic. A pedicled rectus abdominis myocutaneous flap with incorporated
      vascularized rib graft is described as a last resort approach for simultaneous
      reconstruction of the mandible and oral soft tissue.

PMID- 7735677
TI  - EMLA cream on the ears--is it effective? A prospective, randomised controlled
      trial of the efficacy of topical anaesthetic cream in reducing the pain of local
      anaesthetic infiltration for prominent ear correction.
AB  - A prospective, randomised, double blind trial was carried out to test whether or
      not the application of topical anaesthetic cream (EMLA cream) before infiltration
      of local anaesthetic would decrease the discomfort of correction of prominent
      ears under local anaesthetic. 23 patients were entered into the trial. They acted
      as their own controls, one ear having EMLA cream applied approximately 2 h prior
      to surgery, and the other Aqueous cream. Immediately after surgery, the patients
      were asked to complete two scales describing the amount of pain they had felt in
      each ear, both at the time of injection of local anaesthetic and during the
      surgery. They were also asked whether they thought the inconvenience associated
      with the use of the EMLA cream was worth any improvement they felt. The results
      showed that, compared to the placebo cream, EMLA cream significantly decreased
      the pain felt both at the time of injection (p < 0.005) and during the surgery (p
      < 0.01). However, only 62% of patients asked felt that the inconvenience
      associated with the use of EMLA cream was worth the benefits that it conveyed.

PMID- 7735678
TI  - The effect of minoxidil analogues and metabolites on the contraction of collagen
      lattices by human skin fibroblasts.
AB  - Minoxidil, in addition to its effect on hypertension and hair growth, has been
      proposed as a potential antifibrotic agent. Minoxidil inhibits the contraction of
      collagen lattices by human fibroblasts in vitro. However, the mechanism of
      inhibition is unknown. As minoxidil is metabolised in the body to minoxidil
      glucuronide and minoxidil sulphate, we investigated the potencies of these
      metabolites to inhibit collagen lattice contraction. We also studied selected
      analogues of minoxidil to assess the influence of certain functional groups in
      the inhibition. The major metabolite, minoxidil glucuronide, proved to be
      inactive, whereas minoxidil sulphate was considerably more active than minoxidil.
      In terms of the structural analogues, the substitution of one amino group by a
      methyl group resulted in loss of the inhibitory activity; removal of the
      nitroxide oxygen led to stronger inhibition than with minoxidil. Further studies
      are planned to learn more about a possible role for minoxidil in wound
      contraction.

PMID- 7735679
TI  - An adipofascial turnover flap for soft tissue cover around the clavicle.
AB  - Skin defects overlying a clavicular fracture are uncommon. Soft tissue cover is
      essential to avoid osteomyelitis and non-union. We present two cases of exposed
      fractures of the middle third of clavicle following osteosynthesis. Soft tissue
      cover was provided by an adipofascial turnover flap based on the inferior edge of
      the defect. The flap was raised with considerable ease and its vascular supply
      was reliable. There was minimal donor site morbidity and the aesthetic outcome of
      the reconstructions was excellent.

PMID- 7735680
TI  - Morphological aspects of microarterial anastomoses: a comparison of nylon with
      polydioxanone.
AB  - The morphological appearance of longitudinally sectioned rat femoral arteries was
      determined in intact arteries and from 3 to 435 days after vessel division and
      anastomosis with either 9/0 gauge nylon or polydioxanone (PDS) in 26 animals. The
      purpose of the study was to establish the mechanisms and compare the quality of
      healing after microarterial anastomosis and to determine whether PDS was degraded
      before sufficient anastomotic healing had taken place. The results revealed that
      there was no difference in the process of healing or quality of anastomosis with
      either suture material. From 3 to 21 days post anastomosis, there was a
      progressive separation of the ends of vessels within the developing scar.
      Anastomotic patency was established and maintained at first by an adventitial
      overgrowth of fibroblasts and undifferentiated adventitial cells and later by the
      growth of a smooth myocyte scar that stretched between the cut ends of the vessel
      and over the intima in the form of elongated circumferential plaques. The vessel
      was morphologically healed by the 21st day. The sutures served little or no
      purpose in maintaining anastomotic integrity after the 5th day, being situated in
      the scar forming between the separating vessel ends. PDS was present within the
      vessel wall up to 120 days post anastomosis and was certainly intact at the time
      of morphological healing, suggesting that this material is safe as a
      microvascular suture.

PMID- 7735681
TI  - A universal incision for tissue expander insertion.
AB  - A new type of V- or W-shaped intralesional incision for tissue expander insertion
      is presented. The experience with 50 of these incisions in 36 consecutive
      patients in the period 1990-93 without any complication has proved the safety of
      this approach and the advantages of V- or W-shaped incisions over tangential or
      radial incisions.

PMID- 7735682
TI  - Regeneration and wound healing in foetal sheep.

PMID- 7735683
TI  - Potentiation by endothelin-1 of cholinergic nerve-mediated contractions in mouse
      trachea via activation of ETB receptors.
AB  - 1. We have previously shown that endothelin-1-induced contraction of mouse
      isolated tracheal smooth muscle was mediated via both ETA and ETB receptors. In
      the current study, we have investigated endothelin-1-induced potentiation of
      cholinergic nerve-mediated contractions in mouse isolated trachea and have
      characterized pharmacologically the endothelin receptors mediating this response.
      2. Electrical field stimulation (EFS; 70 V, 0.5 ms duration, 10s train, 0.1-60
      Hz) of mouse isolated trachea caused frequency-dependent, monophasic contractions
      (magnitude of contraction of 60 Hz was 56 +/- 4% Cmax (n = 6), where Cmax is the
      contractile response to 10 microM carbachol). EFS-induced contractions were
      abolished by either 0.1 microM atropine or 3 microM tetrodotoxin, but were not
      affected by 1 microM hexamethonium, indicating that they were induced by
      stimulation of postganglionic cholinergic nerves. In contrast, contractions
      induced by exogenously applied acetylcholine were inhibited by atropine, but not
      by either tetrodotoxin or hexamethonium. 3. The ETB receptor-selective agonist,
      sarafotoxin S6c, caused marked concentration-dependent potentiation of EFS
      induced contractions in mouse isolated tracheal segments. At 0.1 nM, sarafotoxin
      S6c exerted no direct contractile effect, but significantly increased a standard
      EFS-induced contraction of 20% Cmax by 8 +/- 2% Cmax (i.e. 1.4 fold, n = 5, P <
      0.05). At higher concentrations, 10 nM sarafotoxin S6c induced a large, transient
      contraction (peak response of 74 +/- 2% Cmax at 10 min; 3 +/- 2% Cmax at 45 min)
      and enhanced the standard EFS-induced contraction by 30 +/- 4% Cmax (i.e. 2.5
      fold, n = 5, P < 0.01). In contrast, 10 nM sarafotoxin S6c did not enhance
      contractile responses to exogenously applied acetylcholine(n = 6).4. Endothelin-1
      also modulated EFS-induced contractions. At 0.1 nM, endothelin-1 exerted no
      direct contractile effect, but significantly increased the standard EFS-induced
      contraction of 20%Cmax, by 7 +/- 2%Cma, (i.e. 1.35 fold, n = 5, P<0.05). At 1 nM,
      endothelin-l induced a small, sustained contraction(16 +/- 3%Cmo) and increased
      the standard EFS-induced contraction by 19 +/- 2%Cmax (i.e. 1.95 fold,n = 5, P
      <0.01). Finally, 10 nM endothelin-1 induced a large, sustained contraction (98 +/
      8%Cma), but the EFS-induced contraction was significantly reduced from 20%Cmax
      to 6 +/- 4%Cmax (n = 6, P <0.05).In contrast, in the presence of 3 microM BQ-123
      (ETA receptor-selective antagonist), 1O nM endothelin-1 induced a transient
      contraction mediated via ETB receptors (peak response of 59 +/- 10%Cmax at 10
      min;8 +/- 2%Cmax at 45 min). Under these conditions, the standard EFS-induced
      contraction was increased by 26+/- l%Cmax (i.e. 2.3 fold, n = 6, P<0.01).5. The
      potentiation of EFS-induced contractions produced by 1 nM endothelin-1 was not
      mediated by ETA receptors, since 3 microM BQ-123 did not diminish this effect (n
      = 6). Furthermore, 1 nM endothelin-1 did not potentiate EFS-induced contractions
      in preparations in which the function of the ETB receptor effector system had
      been attenuated by desensitization (n = 6).6. In summary, endothelin-1
      potentiates cholinergic nerve-mediated contractions in mouse isolated trachea,
      apparently by activating prejunctional ETB receptors. This neuronal pathway
      offers an additional mechanism through which endothelin-1 may elevate
      bronchomotor tone.

PMID- 7735684
TI  - Regional haemodynamic effects of human and rat adrenomedullin in conscious rats.
AB  - 1. Male, Long Evans rats were chronically instrumented with pulsed Doppler flow
      probes and intravascular catheters to permit assessment of the regional
      haemodynamic responses to human and rat adrenomedullin, to compare the responses
      to human adrenomedullin to those of human alpha-CGRP in the absence and presence
      of the CGRP1-receptor antagonist, human alpha-CGRP [8-37], and to determine the
      involvement of nitric oxide (NO)-mediated mechanisms in the responses to human
      adrenomedullin, relative to human alpha-CGRP. 2. Human and rat adrenomedullin
      (0.3, 1, and 3 nmol kg-1, i.v.) caused dose-dependent hypotension and
      tachycardia, accompanied by increases in renal, mesenteric and hindquarters flows
      and vascular conductances. At the lowest dose only, the hypotensive and
      mesenteric vasodilator effects of rat adrenomedullin were significantly greater
      than those of human adrenomedullin. 3. Human alpha-CGRP at a dose of 1 nmol kg-1
      caused hypotension, tachycardia and increases in hindquarters flow and vascular
      conductance, but reduction in renal and mesenteric flows, and only transient
      vasodilatations in these vascular beds. These effects were substantially
      inhibited by human alpha-CGRP [8-37] (100 nmol kg-1 min-1), but those of human
      adrenomedullin (1 nmol kg-1) were not; indeed, the mesenteric haemodynamic
      effects of the latter peptide were enhanced by the CGRP1-receptor antagonist. 4.
      In the presence of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L
      NAME, 183 nmol kg-1 min-1), there was only a slight, but significant, inhibition
      of the hindquarters hyperaemic vasodilator effect of human adrenomedullin, but
      not that of human alpha-CGRP. 5. These results indicate that the marked regional
      vasodilator effects of human (and rat) adrenomedullin are largely independent of
      NO and, in vivo, do not involve CGRP1-receptors.

PMID- 7735685
TI  - Interaction of human adrenomedullin 13-52 with calcitonin gene-related peptide
      receptors in the microvasculature of the rat and hamster.
AB  - 1. Adrenomedullin (ADM), a recently discovered circulating hypotensive peptide,
      shares limited sequence homology with the sensory nerve-derived vasodilator,
      calcitonin gene-related peptide (CGRP). This study compared the vasodilator
      effect of sequence 13-52 of human adrenomedullin (ADM13-52) with that of human
      alpha CGRP (CGRP), in the microvasculature of the hamster cheek pouch and rat
      skin in vivo. 2. Single arterioles (20-40 microns diameter) in the hamster cheek
      pouch were visualised by intravital microscopy and video recording, and measured
      by image analysis. Both ADM13-52 (1 pmol-0.4 nmol) and CGRP (0.1 pmol-1 nmol)
      evoked dose-related increases in the diameter of preconstricted arterioles (n =
      6). ADM13-52 (ED50 14 pmol) was 20 fold less active than CGRP (ED50 0.71 pmol).
      The kinetics of onset and decline of vasodilator responses to both peptides were
      similar, with vasodilator responses to both peptides reaching a maximum at ca. 2
      min, and reversing after 10-15 min (n = 5-7). The submaximal increase in blood
      flow evoked by ADM13-52 was significantly inhibited (P < 0.05; n = 6) by the
      CGRP1 receptor antagonist, CGRP8-37, at a dose (300 nmol kg-1, i.v.) that we have
      previously shown to inhibit significantly equivalent vasodilator responses to
      CGRP in this preparation. 3. In experiments measuring changes in local blood flow
      in rat skin by a 133xenon clearance technique, intradermal injection of both
      ADM13-52 (3-300 pmol) and CGRP (0.1-30 pmol) evoked dose-related increases in
      local blood flow. ADM13-52 (ED50 27 pmol) was 17 fold less potent than CGRP
      (ED501.6 pmol) (n = 6). The submaximal increase in blood flow evoked by both
      peptides was significantly inhibited (P<0.02; n = 5) by CGRP837 (100 nmol kg-1,
      i.v.).4. We conclude that ADM13-52 is a potent vasodilator in the
      microvasculature of the hamster and rat invivo. It mediates its vasodilator
      effect by arteriolar dilatation and this effect is due, at least in part, to the
      stimulation of CGRPI receptors.

PMID- 7735686
TI  - On the inhibition of prostanoid formation by SK&F 96365, a blocker of receptor
      operated calcium entry.
AB  - 1. The proposed blocker of receptor-operated calcium channels, SK&F 96365 was
      shown to inhibit formation of prostaglandin E2 in two osteoblast-like cell lines,
      MC3T3-E1 and UMR-106 in a dose-dependent manner at an IC50 of 3-4 microM.
      Inhibition was observed with various stimuli (arachidonic acid, bradykinin and
      calcium ionophore A23187). 2. This effect was also observed in human platelets,
      where SK&F 96365 dose-dependently blocked thromboxane biosynthesis and formation
      of 12-hydroxy-heptadecatrienoic acid after stimulation with arachidonic acid
      (IC50 = 4 microM). 3. The compound had no effect on 12-hydroxy-eicosatetraenoic
      acid production by human platelets. Additionally, linoleic acid oxidation by
      soybean 15-lipoxidase was not impaired by SK&F 96365. The results thus provide
      evidence for cyclo-oxygenase inhibition by SK&F 96365 at concentrations used to
      block receptor-operated calcium influx.

PMID- 7735687
TI  - Bradykinin B1 receptors in the rabbit urinary bladder: induction of responses,
      smooth muscle contraction, and phosphatidylinositol hydrolysis.
AB  - 1. The aim of this study was to analyse the pharmacological characteristics, and
      second-messenger coupling-mechanisms, of bradykinin B1 receptors in an intact
      tissue, the rabbit urinary bladder; and to investigate the influence of
      inhibition of endogenous peptidases on kinin activities. 2. In preparations of
      rabbit mucosa-free urinary bladder, at 90 min after mounting of the preparations,
      bradykinin (1 nM-10 microM) evoked contractile responses. In contrast, the B1
      receptor-selective agonist [des-Arg9]-BK (10 mM-10 microM) was only weakly active
      at this time. Contractile responses to [des-Arg9]-BK increased with time of
      tissue incubation in the organ bath, reaching a maximum after 3 h, when the pD2
      estimates were 6.4 +/- 0.3 for bradykinin, and 6.9 +/- 0.2 for [des-Arg9]-BK. 3.
      Once stabilized, responses to [des-Arg9]-BK in the bladder were competitively
      antagonized by the B1 receptor-selective antagonists [Leu8,des-Arg9]-BK and D-Arg
      [Hyp3,Thi5,D-Tic7,Oic8,des-Arg9]-BK ([des-Arg10]-Hoe140) (pKB estimates were 6.1
      +/- 0.1 and 7.1 +/- 0.1, respectively; n = 17-21), but responses were unaffected
      by the B2 receptor-selective antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK (Hoe140)
      (100 nM; n = 4). Contractile responses to bradykinin itself were partially, but
      significantly, inhibited by the B1 receptor-selective antagonist, [Leu8,des-Arg9]
      BK (10 microM) (P < 0.05), or by the B2 receptor-selective antagonist Hoe140 (100
      nM) (P < 0.005) alone, and were largely blocked by a combination of the two
      antagonists (P < 0.0001). 4. The combined presence of the carboxypeptidase
      inhibitor DL-2-mercaptomethyl-3-guanidinoethylthiopropanoicacid (mergetpa; 10
      microM), the neutral endopeptidase inhibitor, phosphoramidon (1 microM),and the
      angiotensin-converting enzyme inhibitor, enalaprilat (1 microM) increased the
      potency of bradykinin17 fold (P<0.001), but that of [des-Argl-BK was unchanged
      (P>0.05): pD2 estimates were 7.6 +/- 0.1 and 6.8 +/- 0.1 for bradykinin and [des
      Argl-BK, respectively, in treated preparations. In the presence of peptidase
      inhibitors, the affinities of the antagonists [Leu8,des-Arg9]-BK and [des-Arg'j
      Hoel4O were unchanged as compared with those determined in the absence of
      peptidase inhibitors (P> 0.05).[Leu8,des-Argj-BK inhibited responses to
      bradykinin under these conditions (n = 4).5. In endothelium-denuded preparations
      of the rabbit isolated aorta, an archetypal B1 receptor preparation,contractile
      responses to the B1 receptor-selective agonist [des-Argl-BK (10nM- 1O0 AM) (and
      to bradykinin) increased progressively with time of tissue incubation; and [des
      Argl-BK responses were completely antagonized by the B. receptor antagonist
      [Leu8,des-Arg9]-BK (pKB 6.3 +/- 0.2; n = 13).6. In experiments measuring
      stimulation of hydrolysis of phosphatidylinositol in rabbit urinary bladder,[des
      Argl-BK (10 microM- 1 mM), and bradykinin (100 microM) significantly increased
      accumulation of inositol phosphates (P<0.0001). The increase in accumulation of
      inositol phosphates evoked by [des-Arg9]-BK(10 microM - 1 mM) was significantly
      inhibited by [des-Arg'j-Hoe 140 (10 microM) (P <0.01).7. We conclude that in the
      mucosa-free rabbit urinary bladder, [des-Argl-BK evokes contraction largely via
      activation of B1 receptors which have similar properties, including time
      dependent induction,to B1 receptors in the rabbit isolated aorta. Bradykinin
      evokes contraction via stimulation of both B1 and B2 receptors, but does not
      require conversion by peptidases in order to activate B1 receptors. We
      demonstrate, for the first time, B1 receptor-coupling to phosphatidylinositol
      hydrolysis in an intact tissue preparation.

PMID- 7735688
TI  - Structural requirements at the melatonin receptor.
AB  - 1. High affinity, specific binding sites for the pineal hormone, melatonin (5
      methoxy N-acetyltryptamine) can be detected in chick brain membranes by use of
      the radiolabelled agonist, 2-[125I]-iodomelatonin (2-[125I]-aMT). 2. The affinity
      of a number of analogues of melatonin at the 2-[125I]-aMT binding site was
      determined and compared with an analysis of their electronic structure and
      significant quantitative relationships obtained. 3. The best correlations
      indicated that binding affinity was correlated with delta E, the difference
      between the frontier orbital energies, and QNH, the electron density in the
      highest occupied molecular orbital of the side-chain nitrogen atom. 4. These
      findings suggest that ligand binding may involve hydrogen bonding between the 5
      methoxy and amide moieties of melatonin and complementary amino acid residues,
      and charge transfer interactions between the indole ring of melatonin and an
      aromatic amino acid in the receptor binding site. 5. A molecular model of a
      putative binding site is proposed based on the predicted amino acid sequence of
      the cloned Xenopus laevis melanophore melatonin receptor and the quantitative
      structure-affinity relationships observed in the present study.

PMID- 7735689
TI  - Effect of crilvastatin, a new cholesterol lowering agent, on unesterified LDL
      cholesterol metabolism into bile salts by rat isolated hepatocytes.
AB  - 1. The aim of these experiments was to determine the effect of crilvastatin, a
      new cholesterol lowering agent, on the metabolism of unesterified low density
      lipoprotein (LDL)-cholesterol by rat freshly isolated hepatocytes. This
      preclinical model was developed as an alternative to in vivo experiments, to
      mimic the metabolic effects of a molecule on its target cells and to define
      optimal conditions for future experimentation on human hepatocytes. 2. Cells were
      obtained from normolipidaemic or hypercholesterolaemic rats,
      hypercholesterolaemia was nutritionally induced. Incubations were performed in a
      medium containing 600 microM taurocholate and 50 microM or 300 microM
      crilvastatin. 3. This molecule was shown in vitro to be carried by physiological
      transporters, i.e., albumin-bile salt micellar associations and LDL. Crilvastatin
      induced a significance increase in the synthesis and secretion by hepatocytes of
      bile salts resulting from the metabolism of unesterified LDL-cholesterol in both
      normolipidaemic and hypercholesterolaemic rats. Stimulation involved non
      conjugated as well as tauro- and glyco-conjugated bile salts. These findings
      corroborate preliminary studies showing in vivo that crilvastatin enhances the
      secretion of bile acids by stimulating the uptake and incorporation of LDL
      cholesterol by the liver.

PMID- 7735690
TI  - Effects of divalent cations and La3+ on contractility and ecto-ATPase activity in
      the guinea-pig urinary bladder.
AB  - 1. Several cations (Ba2+, Cd2+, Co2+, Cu2+, Mn2+, Ni2+, Zn2+ and La3+, all as
      chloride salts, 1-1000 microM) were tested in the guinea-pig urinary bladder for
      their ability to: (i) modify contractile responses to electrical field
      stimulation (EFS), ATP, alpha,beta-methylene ATP (alpha,beta-meATP), carbachol
      (CCh), and KCl; (ii) affect ecto-ATPase activity. 2. Ba2+ (10-1000 microM)
      concentration-dependently potentiated contractile responses evoked by EFS (4-16
      Hz), ATP (100 microM), alpha,beta-meATP (1 microM), CCh (0.5 microM), and KCl (30
      mM). Ni2+ at concentrations of 1-100 microM also potentiated contractility of the
      urinary bladder, but at concentrations tested its effect was not concentration
      dependent. Cu2+ at a concentration of 10 microM and Cd2+ at a concentration of 1
      microM potentiated responses to all stimuli, except KCl. Ni2+ at a concentration
      of 1000 microM and Cd2+ at a concentration of 100 microM inhibited contractions
      evoked by all stimuli, and at a concentration of 1000 microM Cd2+ abolished any
      contractions. Responses to ATP and alpha,beta-meATP were selectively inhibited by
      Cu2+, Zn2+ or La3+, each at a concentration of 1 mM. 3. Cu2+, Ni2+, Zn2+ and La3+
      (100-1000 microM) concentration-dependently inhibited ecto-ATPase activity in the
      urinary bladder smooth muscle preparations, while Ba2+ and Mn2+ were without
      effect, and Cd2+ and Co2+ caused significant inhibition only at a concentration
      of 1000 microM. 4. There was no correlation between the extent of ecto-ATPase
      inhibition and the effect on contractile activity of any of the cations. 5. In
      conclusion, the ability of some divalent cations to inhibit ecto-ATPase activity
      and to potentiate or inhibit contractile responses in the guinea-pig urinary
      bladder appear to be independent effects.

PMID- 7735691
TI  - Inhibition by cyclothiazide of neuronal nicotinic responses in bovine chromaffin
      cells.
AB  - 1. The desensitizing acetylcholine (ACh) response of bovine chromaffin cells
      maintained in culture was examined using rapid agonist applications (of 2 s
      duration) which imposed nominal drug concentrations within 50 ms. This study was
      aimed, firstly, at identifying which of the alpha 3, alpha 4 and alpha 7 subunits
      known to be present in these cells is predominant in the ACh-evoked response and
      secondly, on the effects on these neuronal nicotinic ACh receptors (AChR) of
      cyclothiazide (CT), an agent acting as a modulator of a gating desensitization
      site on other ligand-gated channels. 2. Locally applied 100 microM ACh evoked
      peak currents (IACh) of -1.5 +/- 0.1 nA (n = 83) at a holding potential of -60
      mV. The ACh dose-response curve yielded an estimated EC50 of 60 microM. This
      current was not sustained but desensitized during the application period; it
      displayed strong inward rectification, but desensitized equally whether the
      evoked current was inward or outward going. The latter observation excludes alpha
      4 as a major contributor to the recorded current. Because the response was almost
      insensitive to a 1 microM alpha-bungarotoxin pretreatment (IACh = -1.2 +/- 0.1
      nA; n = 6), and because 1, 1-dimethyl-4-phenylpiperazinium (DMPP) works as a
      potent agonist (peak current = -1.9 nA, n = 2 for 100 microM DMPP), the alpha 7
      subunit is also a minor contributor to the response. Taken together, these
      observations suggest a dominant alpha 3 type of response. 3. Triple exponential
      fits were used to describe the characteristics of the ACh-evoked currents; one
      component to fit the rising phase, with 2 components to describe the decay phase.
      The decay times were 100 ms and 4 s for the fast and slow components
      respectively. The rate of the slow decay component increased systematically with
      recording time, approximately doubling from its initial value within 20-40 min.
      Furthermore there was a gradual rundown of the response, seen first as a loss of
      the late component of the current, measured at 2 s, with the peak current
      amplitude decreasing later in the recording.4. CT, when coapplied with ACh,
      produced a dose-dependent inhibition of the ACh-evoked peak current. The effect
      showed little voltage-dependency with 100 microM CT producing 46 +/- 5% (s.d.; n
      = 3)and 47 +/- 8% (s.d.; n = 7) inhibition at -100 and -60 mV respectively. At +
      60 mV, inhibition was estimated to be 26 +/- 7% (s.d.; n = 3).5. After pre
      exposure of the cells to CT by bath application, 10 and 30 microM CT produced
      poorly reversible 20 +/- 9% (n = 7) and 42 +/- 5% (n = 4) inhibitions of the peak
      current respectively. There were no discernible effects on the fitted decay
      constants at any CT concentration tested, although an increased inhibitory effect
      of CT was observed at higher concentrations (100 microM) on the amplitude of the
      late component measured at 2 s.6. Similar effects were observed in conditions
      chosen to isolate the alpha 3 type of receptor: namely when using DMPP as an
      agonist, or after a-bungarotoxin pretreatment.7. The 2,3-benzodiazepine, GYKI
      53655, is known to antagonize the action of CT on AMPA receptors.Coapplication of
      50 microM GYKI 53655 with ACh (100 microM) produced a 29 +/- 4% inhibition of the
      peak ACh-evoked current and 44 +/- 6% inhibition of its amplitude at 2 s (n = 4).
      This response was fully reversible. Brief applications of both CT (100 microM)
      and GYKI 53655 (50 microM) with ACh via the microperfusion system produced a
      fully reversible inhibition that was not significantly different from the values
      obtained with either CT or GYKI 53655 alone, with 37 +/- 6% inhibition of peak
      and 61 +/- 9%inhibition of the amplitude at 2 s (n = 3).8. The results obtained
      suggest that the CT effect is to impede recovery from a slow desensitization,with
      a more pronounced effect with longer CT applications. Globally, CT favours the
      'rundown state' of the neuronal nicotinic AChR.

PMID- 7735692
TI  - Cardiovascular effects of the calcium sensitizer, levosimendan, in heart failure
      induced by rapid pacing in the presence of aortic constriction.
AB  - 1. The haemodynamic effects of a novel cardiotonic drug, levosimendan, which has
      both calcium-sensitizing and phosphodiesterase III (PDE III) inhibitory
      properties, were studied in conscious dogs in which heart failure had been
      induced by prolonged cardiac pacing in the presence of aortic constriction. These
      effects were compared with those in sham-operated dogs with essentially normal
      cardiac function. 2. Eighteen mongrel dogs were instrumented for the measurement
      of left ventricular pressure (LVSP, LVEDP) and contractile function (dP/dt;
      dP/dt/P). In twelve dogs a balloon catheter, positioned in the thoracic aorta,
      was inflated producing an approximate 60% reduction in effective aortic diameter.
      Twenty min later rapid ventricular pacing (240 beats mean-1) was commenced and
      maintained for 48 h by means of a bipolar pacing electrode introduced into the
      right ventricle. This electrode served also for recording changes in the
      endocardial electrogram in the absence of pacing. Six of these dogs were used to
      evaluate the haemodynamic changes of pacing-induced heart failure; a further six
      of these dogs the haemodynamic changes elicited by levosimendan under these
      conditions. Six sham-operated dogs (group 2) served as controls. 3. In six dogs
      (group 1) the haemodynamic alterations were assessed after the development of
      heart failure. In the presence of aortic constriction, 48 h continuous rapid
      cardiac pacing resulted in a marked deterioration in left ventricular function
      which remained stable for at least 48 h after cessation of pacing. Thus, there
      was a marked reduction in LVSP (15%), +dP/dtmax (35%), -dP/dtmax (36%) and also
      in dP/dt/P (29%), whereas LVEDP was increased considerably (from 6.4 +/- 1.4 to
      20.0 +/- 2.2 mmHg). A marked elevation occurred in endocardial ST-segment (138%),
      lasting for 20 min.4. Levosimendan was administered intravenously in doses of
      0.005, 0.01 and 0.03 micromol kg-1 to 2 groups of conscious dogs. In the sham
      operated dogs (group 2), only the higher dose (0.03 micromol kg-1)produced
      significant increases in LVSP (19%), + dP/dtmax (37%), and in dP/dt/P (32%). In
      dogs with heart failure (group 3) doses of 0.005, 0.01 and 0.03 micromol kg-1
      levosimendan resulted in an improve mentin +dP/dtmax (26%, 38% and 49%), 
      dP/dtmax (20%, 25% and 38%) and in dP/dt/P (19%, 34%and 50%) and reduction in the
      elevated LVEDP (from 20 =/- 2.2 mmHg to 16 +/- 1.0, 10 +/- 1.3 and 9 +/- 1.0
      mmHg, respectively).5. Levosimendan proved to be a potent cardiotonic drug at the
      doses used, and was approximately three times more effective under conditions of
      impaired left ventricular function than in normal hearts.

PMID- 7735693
TI  - Activation by intracellular GDP, metabolic inhibition and pinacidil of a
      glibenclamide-sensitive K-channel in smooth muscle cells of rat mesenteric
      artery.
AB  - 1. Single-channel recordings were made from cell-attached and isolated patches,
      and whole-cell currents were recorded under voltage clamp from single smooth
      muscle cells obtained by enzymic digestion of a small branch of the rat
      mesenteric artery. 2. In single voltage-clamped cells 1 mM uridine diphosphate
      (UDP) or guanidine diphosphate (GDP) added to the pipette solution, or pinacidil
      (100 microM) a K-channel opener (KCO) applied in the bathing solution, evoked an
      outward current of up to 100pA which was blocked by glibenclamide (10 microM). In
      single cells from which recordings were made by the 'perforated patch' (nystatin
      pipette) technique, metabolic inhibition by 1 mM NaCN and 10 mM 2-deoxy-glucose
      also evoked a similar glibenclamide-sensitive current. 3. Single K-channel
      activity was observed in cell-attached patches only infrequently unless the
      metabolism of the cell was inhibited, whereupon channel activity blocked by
      glibenclamide was seen; pinacidil applied to the cell evoked similar
      glibenclamide-sensitive channel activity. If the patch was pulled off the cell to
      form an isolated inside-out patch, similar glibenclamide-sensitive single-channel
      currents were observed in the presence of UDP and/or pinacidil to those seen in
      cell-attached mode; channel conductance was 20 pS (60:130 K-gradient) and
      openings showed no voltage-dependence and noisy inward currents, typical of the
      nucleoside diphosphate (NDP) activated K-channel (KNDP) seen previously in rabbit
      portal vein. 4. Formation of an isolated inside-out patch into an ATP-free
      solution did not increase the probability of channel opening which declined with
      time even when some single-channel activity had occurred in the cell-attached
      mode before detachment. However, application of 1 mM UDP or GDP, but not ATP, to
      inside-out patches evoked single-channel activity. Application of ATP-free
      solution to isolated patches, previously exposed to ATP and in which channel
      activity had been seen, did not evoke channel activity. 5. It is concluded that
      small conductance K-channels (KNDP) open in smooth muscle cells from this small
      artery in response to UDP or GDP acting from the inside, or pinacidil acting from
      the outside; the same channels open during inhibition of metabolism presumably
      mainly due to the rise in nucleoside diphosphates, but a fall in the ATP
      concentration on the inside of the channel did not by itself evoke channel
      activity. Failure to respond to a fall in ATP concentration upon formation of an
      inside-out patch could not be due to dephosphorylation of the channel because
      sometimes it had been active previously during cell-attached recording. NDPs,
      instead of ATP, are more important regulators of KNDP channels. It is suggested
      that the KNDP is the main target K-channel for KCOs.

PMID- 7735694
TI  - Sustained negative inotropism mediated by alpha-adrenoceptors in adult mouse
      myocardia: developmental conversion from positive response in the neonate.
AB  - 1. Inotropic responses to alpha-adrenoceptor stimulation and the effects of
      antagonists were examined in isolated ventricular preparations from neonatal and
      adult mice. 2. Phenylephrine, in the presence of propranolol, produced positive
      inotropic responses in neonates up to 1 week after birth, while it produced
      negative inotropic responses in mice older than 3 weeks. 3. Both positive and
      negative responses to phenylephrine in neonates and adults, respectively, were
      antagonized by prazosin, WB4101 (2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4
      benzodioxane) and 5-methylurapidil, but not by atropine, yohimbine or
      chlorethylclonidine. 4. Noradrenaline (NA) produced positive inotropic responses
      both in the neonate and adult; the responses were observed in a lower
      concentration-range in the neonate than in the adult. WB4101 produced a
      significant leftward shift of the concentration-response curve for noradrenaline
      in adult preparations while only a slight rightward shift was observed in the
      neonate. 5. Our results demonstrate the presence of alpha-adrenoceptor-mediated
      inotropic responses in the mouse ventricular myocardia. The response to
      phenylephrine changes from a positive to a negative effect during postnatal
      development. The responses are mediated by alpha 1-adrenoceptors, and modulate
      the overall inotropic response to NA in the adult.

PMID- 7735695
TI  - The relationship between density of alpha-adrenoceptor binding sites and
      contractile responses in several porcine isolated blood vessels.
AB  - 1. The aim of this study was to investigate constrictor alpha-adrenoceptors in
      three isolated blood vessels of the pig, the thoracic aorta (TA), the splenic
      artery (SA) and marginal ear vein (MEV) and then compare the functional response
      with the densities of alpha 1- and alpha 2-adrenoceptor binding sites in these
      and several other porcine vascular tissues, palmar common digital artery (PCDA),
      palmar lateral vein (PLV) and ear artery (EA). 2. Noradrenaline (NA),
      phenylephrine (PE) and UK14304 (all at 0.03-10 microM) elicited concentration
      dependent contractions in the TA and MEV, with a rank order of potency of UK14304
      > NA > PE. UK14304 produced maximal responses which were 58% (TA) and 65% (MEV)
      of that of NA. In the SA, UK14304 and PE produced maximal responses which were
      less than 10% and 50% of the NA-induced maximal response respectively, with an
      order of potency of NA > PE. In the SA, NA-induced contractions were
      competitively antagonized by prazosin (pA2 = 8.60 +/- 0.15). Further, rauwolscine
      (1-10 microM) antagonized NA-induced contractions with an apparent pKB of 6.09 +/
      0.11 (n = 6), indicating an action at alpha 1-adrenoceptors. The combination of
      the two antagonists at concentrations selective for alpha 1- (0.1 microM) and
      alpha 2-adrenoceptors (1 microM) had no greater effect than either antagonist
      alone. This suggests that the SA expresses only post-junctional alpha 1
      adrenoceptors. 3. In the TA, prazosin produced non-parallel shifts in the NA
      induced CRC and this was also observed with rauwolscine, where reductions in the
      maximal responses were also observed. In the MEV, prazosin was largely inactive
      in antagonizing NA-induced contractions. In both these vessels a combination of
      these two antagonists had a greater effect than either alone, indicating the
      presence of functional alpha 1- and alpha 2-adrenoceptors. The post-junctional
      alpha 2-adrenoceptors in all of these vessels were resistant to prazosin,
      suggesting the alpha 2-adrenoceptor to be of the alpha 2A/2D subtype. The
      expression of functional alpha 2-adrenoceptors was MEV > TA > PLV > PCDA > SA. 4.
      In radioligand binding studies using TA P2 pellet membranes, [3H]-prazosin and
      [3H]-RX821002 ([1,4-[6,7(n)-3H] benzodioxan-2-methoxy-2-yl)-2-imidazole) labelled
      different high affinity sites, and in competition studies using identical
      membranes corynanthine displaced [3H]-prazosin with 10 fold higher affinity than
      rauwolscine, indicating that [3H]-prazosin was selectively binding to alpha 1
      adrenoceptor sites. Further, rauwolscine displaced [3H]-RX821002 with
      approximately 100 fold greater affinity compared to corynanthine, which is
      indicative of selective alpha2-adrenoceptor binding.5. Separation of the P2
      pellet into plasma membrane and mitochondrial fractions was carried out using a
      differential sucrose density gradient. [3H]-prazosin and [3H]-RX821002 binding
      sites were found in both the plasma membrane and mitochondrial fractions.6. In
      saturation studies all tissues produced single site saturation curves with no
      difference in the Kd(range 0.13-0.20nM) of the alpha1-adrenoceptor sites for [3H]
      prazosin. However, there was considerable variation in Bmax of alpha 1
      adrenoceptor sites; the highest density was found in the TA (397.9 =/- 52.7 fmol
      mg-1, n = 4), followed by the PCDA (256.7 +/- 22.7 fmol mg-1, n = 4), the PLV and
      SA having approximately equal density (143.6 +/- 3.9 and 159.1 +/- 7.0 fmol mg-1
      respectively, n = 4 for both), followed bythe EA (91.3 +/- 10.5 fmol mg-1, n = 3)
      and the MEV had the lowest density (48.9 +/- 11.4 fmol mg-1,n = 3).7. In
      saturation studies using [3H]-RX821002, all tissues produced single site
      saturation curves with no differences in the Kd values (range 1.31 +/- 2.16 nM)
      but the highest densities were found in the TA and MEV (545.3 +/- 36.2 and 531.0
      +/- 40.9 fmol mg-1 respectively), followed by the PLV (418.4 +/- 39.4 fmol mg-1),
      then the EA (266.3 +/- 40.0 fmol mg-1), and low densities of [3H]-RX821002
      binding being found in the PCDA and SA (155.9 +/- 18.1 and 117.5 +/- 19.3 fmol mg
      1 respectively).8. The pattern of binding site distribution for alpha l- and
      alpha 2-adrenoceptors is in reasonable agreement with functional studies carried
      out in these porcine vascular tissues; the TA has the highest densities of alpha
      1-and alpha2-adrenoceptors; in the SA and PCDA there is a predominance (although
      small) of alpha l-adrenoceptor binding sites, the reverse of which is observed
      both in the PLV and MEV (i.e. greater density of alpha2-adrenoceptor sites).
      Thus, it would appear that alpha 1- and alpha2-adrenoceptor densities play a role
      in the expression of functional responses via these receptor subtypes; although
      it is interesting to note that the SA did have a small density of alpha 2
      adrenoceptor binding sites, no functional response was observed after alpha2
      adrenoceptor activation.

PMID- 7735696
TI  - Pharmacological characterization of noradrenaline-induced contractions of the
      porcine isolated palmar lateral vein and palmar common digital artery.
AB  - 1. The aim of this study was to examine the pharmacological characteristics of
      alpha-adrenoceptor-mediated contractions in two porcine isolated blood vessels,
      the palmar lateral vein (PLV) and the palmar common digital artery (PCDA). This
      was carried out with noradrenaline used as the agonist throughout, and either
      phentolamine (non-selective alpha-adrenoceptor antagonist), prazosin and YM-12617
      (selective alpha 1-adrenoceptor antagonists) or rauwolscine and CH-38083
      (selective alpha 2-adrenoceptor antagonists). 2. Noradrenaline (0.003-10 microM)
      produced concentration-dependent contractions in both vessels, with the PCDA (pD2
      = 6.33 +/- 0.07, n = 10) being approximately 10 fold less sensitive to
      noradrenaline compared to the PLV (pD2 = 7.39 +/- 0.09, n = 8). Also, the maximal
      response to noradrenaline was greater in the PCDA compared to the PLV.
      Phentolamine (0.03-30 microM) produced parallel rightward shifts in the CRC to
      noradrenaline in both tissue preparations. The pA2 values were similar and slopes
      of the Schild plots were not significantly different from unity, indicating an
      interaction between phentolamine and a single receptor in each preparation. 3. In
      the PCDA the alpha 1-adrenoceptor antagonists, prazosin (0.01-1 microM) and YM
      12617 (0.01-1 microM) produced non-parallel rightwards shifts in the CRC to
      noradrenaline, with the lower 10-15% of the CRC exhibiting greater resistance to
      the effects of these antagonists compared to the upper part. In contrast,
      rauwolscine (1-10 microM) and CH-38083 (10 microM) produced parallel displacement
      of the CRC to noradrenaline. In the PLV, low concentrations of either alpha l-
      (0.01 microM) or alpha2-adrenoceptor antagonists(0.1-1 microM) produced a large
      shift in the CRC, but subsequent higher concentrations had only small additional
      effects. Based upon pKB values estimated from the effects of the lower
      concentrations of antagonists, the results are consistent with a large population
      of alpha1-adrenoceptors in the PCDA and a mixture of alpha l- and alpha2
      adrenoceptors in the PLV.4. In both tissues, when an ac,- and an a2-adrenoceptor
      antagonist were used in combination the effect produced was greater than that
      with either agent alone. In contrast, the combination of the alpha1-adrenoceptor
      antagonists (prazosin and YM-12617 together) or the alpha2-adrenoceptor
      antagonists (CH-38083 and rauwolscine together) were no more effective than that
      produced by the individual antagonists. These findings suggest the presence of
      functional alpha l- and alpha2-adrenoceptors in the PLV andPCDA.5.
      Phenoxybenzamine (0.3-3 microM, 60min exposure) produced a concentration
      dependent reduction in the maximal response to noradrenaline which was more
      pronounced in the PCDA than the PLV. After a 60 min exposure to a combination of
      phenoxybenzamine (1 microM) and rauwolscine (1 microM), the remaining NA-induced
      contraction after washout was resistant to prazosin (0.1 microM) and sensitive to
      rauwolscine(1 microM) in both tissue preparations, indicating the existence of
      functional alpha2-adrenoceptors in both vessels.6. Evidence suggests that post
      junctional alpha l- and alpha2-adrenoceptors contribute to noradrenaline-induced
      contractions in the PCDA and PLV, with the latter possessing a larger population
      of functional alpha2-adrenoceptors.

PMID- 7735697
TI  - Interaction between methotrexate and indomethacin on a human normal haemopoietic
      cell line.
AB  - 1. The interaction between methotrexate and indomethacin has been examined, at a
      physiological folate concentration (20 nM), on a human normal lymphoblast-like
      cell line (RPMI 1788) in vitro. 2. Indomethacin (1 microgram ml-1) increased the
      reduction of lymphoblast growth caused by methotrexate (10-80 ng ml-1). 3.
      Indomethacin (0.1 and 1 microgram ml-1) potentiated the cytotoxicity of
      methotrexate (20 and 40 ng ml-1) after 4 days in culture. 4. Indomethacin (0.4
      micrograms ml-1) reduced the accumulation of tritium in lymphoblasts incubated
      with [3H]-methotrexate after 30 min; therefore initial drug accumulation was not
      responsible for the potentiation seen after 4 days. 5. If indomethacin increases
      the killing of human cancer cells by methotrexate in vivo, with a smaller
      potentiation on lymphoblasts, this combination may be beneficial in treating
      human malignancy.

PMID- 7735698
TI  - Different pressor and bronchoconstrictor properties of human big-endothelin-1, 2
      (1-38) and 3 in ketamine/xylazine-anaesthetized guinea-pigs.
AB  - 1. In the present study, the precursors of endothelin-1, endothelin-2 and
      endothelin-3 were tested for their pressor and bronchoconstrictor properties in
      the anaesthetized guinea-pig. In addition, the effects of big-endothelin-1 and
      endothelin-1 were assessed under urethane or ketamine/xylazine anaesthesia. 2.
      When compared to ketamine/xylazine, urethane markedly depressed the pressor and
      bronchoconstrictor properties of endothelin-1 and big-endothelin-1. 3. Under
      ketamine/xylazine anaesthesia, the three endothelins induced a biphasic increase
      of mean arterial blood pressure. In contrast, big-endothelin-1, as well as big
      endothelin-2 (1-38), induced only sustained increase in blood pressure whereas
      big-endothelin-3 was inactive at doses up to 25 nmol kg-1. 4. Big-endothelin-1,
      but not big-endothelin-2, induced a significant increase in airway resistance.
      Yet, endothelin-1, endothelin-2 and endothelin-3 were equipotent as
      bronchoconstrictor agents. 5. Big-endothelin-1, endothelin-1 and endothelin-2,
      but not big-endothelin-2, triggered a marked release of prostacyclin and
      thromboxane A2 from the guinea-pig perfused lung. 6. Our results suggest the
      presence of a phosphoramidon-sensitive endothelin-converting enzyme (ECE) which
      is responsible for the conversion of big-endothelin-1 and big-endothelin-2 to
      their active moieties, endothelin-1 and 2. However, the lack of
      bronchoconstrictor and eicosanoid-releasing properties of big-endothelin-2, as
      opposed to endothelin-2 or big-endothelin-1, suggests the presence of two
      distinct phosphoramidon-sensitive ECEs in the guinea-pig. The ECE responsible for
      the systemic conversion of big-endothelins possesses the same affinity for big
      endothelin-l and 2 but not big-endothelin-3. In contrast, in the pulmonary
      vasculature is localized in the vicinity of the sites responsible for eicosanoid
      release, an ECE which converts more readily big-endothelin-1 than big-endothelin
      2.

PMID- 7735699
TI  - Differentiation by pyridoxal 5-phosphate, PPADS and IsoPPADS between responses
      mediated by UTP and those evoked by alpha, beta-methylene-ATP on rat sympathetic
      ganglia.
AB  - 1. The effect of pyridoxal 5-phosphate, and the 2',4' and 2',5'-disulphonic acid
      isomers of 6-azophenylpyridoxal 5-phosphate (PPADS and IsoPPADS respectively) on
      depolarization of the rat superior cervical ganglion evoked by alpha, beta
      methylene-adenosine 5'-triphosphate (alpha, beta-Me-ATP) and uridine 5'
      triphosphate (UTP) were determined by a grease-gap recording technique. 2.
      Pyridoxal 5-phosphate (10-100 microM) and PPADS (10-100 microM) enhanced UTP- and
      depressed alpha, beta-Me-ATP-evoked depolarizations but did not significantly
      alter depolarizations evoked by potassium or hyperpolarizations evoked by
      adenosine. IsoPPADS (10 microM) depressed alpha, beta-Me-ATP-evoked
      depolarizations but did not alter depolarizations evoked by UTP. Depolarizations
      evoked by muscarine were depressed by IsoPPADS but not by pyridoxal 5-phosphate.
      3. It is concluded that pyridoxal 5-phosphate, PPADS and IsoPPADS are antagonists
      at P2x-purinoceptors but not at the receptors that mediate UTP-evoked
      depolarization of the rat superior cervical ganglion. These observations
      substantiate the recent proposal that the rat superior cervical ganglia possess
      distinct receptors for purine and pyrimidine 5'-nucleotides, i.c. P2x
      purinoceptors and pyrimidinoceptors respectively.

PMID- 7735700
TI  - Theoretical calculations of heavy-atom isotope effects.
AB  - An overview of calculations of isotope effects on biochemical and chemical
      reactions using quantum chemistry methods is presented. Usefulness of different
      levels of theoretical scrutiny for such calculations is critically discussed.

PMID- 7735702
TI  - Nutrition and therapeutics.

PMID- 7735701
TI  - Effective fragment potentials and spectroscopy at enzyme active sites.
AB  - Spectroscopy at a biochemical active site is influenced by local fields and
      hydrogen-bonds. Quantum calculations of the electronic structure of the entire
      biomolecule is, of course, impossible, but the chemical system can be modeled by
      dividing it into an active region (A) described quantum mechanically, and a
      spectator region (S) that influences A with strong fields and hydrogen-bonds. The
      all-electron interaction between A and S is replaced by an effective fragment
      potential (EFP) which represents the interaction as electrostatic, polarization
      and exchange repulsion terms. The EFP are derived entirely by ab initio model
      calculations of the S electronic properties and interactions and have been
      implemented in the quantum chemistry code, GAMESS. Spectroscopic analysis of
      enzyme active sites using the EFP will examine rhodanese and glutathione bound to
      glutathione S-transferase. The effect of specific hydrogen-bonds and local
      helices on spectral shifts is determined.

PMID- 7735703
TI  - Nutrition and therapeutics.

PMID- 7735704
TI  - Cardiovascular disease and hyperlipidaemia.

PMID- 7735705
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 7735706
TI  - Clinical chemistry and coagulation.

PMID- 7735707
TI  - Genetics and molecular biology.

PMID- 7735708
TI  - Dietary fibre and blood lipids.
AB  - Sources of dietary fibre can be divided into three groups according to their
      effect on plasma lipids in humans: (1) a cholesterol-lowering effect demonstrated
      repeatedly by pectin, guar gum, psyllium and oat bran (sources of soluble fibre);
      (2) a possible, but not adequate, cholesterol-lowering effect by legumes, barley,
      rice bran and several types of gum; and (3) those sources that do not lower
      plasma cholesterol, such as wheat fibre, cellulose and lignin.

PMID- 7735709
TI  - Antioxidant vitamins and coronary heart disease risk.
AB  - Although considerable evidence shows that high levels of antioxidant vitamins are
      associated with protection against LDL oxidation and cardiovascular disease, the
      only randomized trial performed to date has failed to show any benefit. However,
      modest doses were used and higher doses may be required to show clinical effects.

PMID- 7735710
TI  - Coffee, tea and coronary heart disease.
AB  - The most likely cholesterol-raising factors in unfiltered coffee are kahweol and
      cafestol. Different brewing methods alter the concentrations of these diterpenes
      and have caused discrepant results in studies from different parts of the world.
      The effect of tea on the risk of coronary heart disease is much less clear but
      some studies have found a protective effect, possibly caused by flavonoids acting
      as antioxidants.

PMID- 7735711
TI  - Infant nutrition: effects of lipid on later life.
AB  - Dietary fat alters the phospholipid composition throughout all membranes. The
      functional consequences of these changes are just beginning to be examined in
      relation to infant feeding. Varying the fatty acid composition of formulas
      changes the biochemical and physiological indices linked with growth, vision and
      cognitive function. Further definitive studies are needed to determine the impact
      of early nutrition on infant development.

PMID- 7735712
TI  - Nutrition, lipids and diabetes mellitus.
AB  - The risk of developing obesity, insulin resistance and noninsulin-dependent
      diabetes is influenced by the amount and type of fat in the diet. The choice
      between more monounsaturated fat and more carbohydrate-rich foods in the diabetic
      diet depends on the status and need of the patient.

PMID- 7735713
TI  - An update on lipid-lowering therapy.
AB  - New information on the effects of lipid-lowering drugs is reviewed with an
      emphasis on special groups that benefit from specific drug therapy. Although it
      has been shown that the diet may further enhance the effectiveness of lipid
      lowering drugs, compliance to diet and drugs remains an important issue and the
      large individual variations in dietary responses should be studied more
      extensively. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are
      safe and effective in different populations such as in women, elderly people and
      in special cases of secondary hyperlipidaemia. More widespread implementation of
      screening programmes to identify suitable patients for lipid-lowering therapy may
      help prevent the excess utilization of health care resources.

PMID- 7735714
TI  - Lipoproteins and thrombosis: effects of lipid lowering.
AB  - Evidence continues to accrue for disturbances in coagulation, fibrinolysis and
      platelet behaviour in hyperlipidaemic states, which together might constitute a
      prethrombotic state. Lipid lowering by diet or drug therapy appears to ameliorate
      these disturbances, thus providing one possible mechanism whereby such treatment
      reduces the risk of coronary heart disease in addition to its effects on
      atherogenesis.

PMID- 7735715
TI  - Diets and postprandial lipoproteins.
AB  - The postprandial phase is characterized by a temporary accumulation of
      atherogenic chylomicron remnants and activation of coagulation factor VII. The
      benefits of diets recommended to decrease the risk of coronary heart disease
      should also be evaluated in this respect. Although most of the recent dietary
      studies included a postprandial evaluation, a large majority were conducted using
      conventional methods. Consequently they have only provided a limited insight into
      the changes of the above mentioned risk factors. Furthermore, it should be
      realized that evaluations made under conditions in which an individual is
      prepared for a cholesterol-lowering diet do not provide an accurate risk
      estimation. Thus, evaluations should be performed preferably in the free-living
      situation.

PMID- 7735716
TI  - Diet and drug therapy for lipoprotein (a).
AB  - Lipoprotein (a) has been implicated with an increased risk of atherosclerosis and
      cardiovascular disease. Recently, considerable progress has been made toward
      understanding the importance of genetics in the regulation of plasma levels of
      lipoprotein (a). However, the issue as to whether lipoprotein (a) levels should
      be treated is still debated and furthermore the possibilities to influence
      lipoprotein (a) levels remain limited. The potential clinical importance of
      lipoprotein (a) has stimulated interest in the dietary and pharmacologic agents
      that affect this lipoprotein. At present, only a few of the existing therapeutic
      tools, such as nicotinic acid and estrogens, have been found to consistently
      affect lipoprotein (a).

PMID- 7735717
TI  - Current concepts in the treatment of familial hypercholesterolaemia.
AB  - Molecular biological studies in familial hypercholesterolaemia have indicated
      that the severity of the disease, at least in terms of circulating LDL
      cholesterol levels, varies depending on the kind of structural defect found in
      the LDL receptor gene. This may well influence individual risk and signal that
      more aggressive therapeutic intervention is required. The discovery of the
      statins has revolutionized therapy for the familial hypercholesterolaemia
      heterozygote, but the prognosis for the rare homozygote, who fails to respond
      adequately to therapy, remains poor unless extreme measures are taken.

PMID- 7735718
TI  - Cholesterol lowering and morbidity and mortality.
AB  - Circulating cholesterol is causative in coronary atherosclerosis. Moreover,
      cholesterol lowering has been demonstrated to prevent the progression of
      atherosclerosis. Concern has been expressed, based on primary prevention trials
      and population studies, that cholesterol lowering might cause noncardiovascular
      mortality. When carefully analyzed, however, neither clinical trial data nor
      observational data supported this concern.

PMID- 7735719
TI  - The dietary fat: carbohydrate ratio in relation to body weight.
AB  - A review of the contemporary dietary surveys indicates that the percentage of
      energy derived from fat is, in general, positively associated with total energy
      consumption and obesity. However, dietary carbohydrate tends to show the opposite
      trend. Epidemiological and experimental evidence suggest that the fat:
      carbohydrate ratio affects body weight through energy surfeits facilitated by the
      high energy density and palatability of fat. Biological mechanisms for an effect
      of this dietary ratio on the regulation of body weight have been the topic of
      much recent research. In this context the fat: carbohydrate ratio might be of
      particular importance in individuals with an inherited susceptibility to obesity.

PMID- 7735720
TI  - Analysis of the gene for the elongation factor 1 alpha from the zygomycete
      Absidia glauca. Use of the promoter region for constructions of transformation
      vectors.
AB  - The complete genomic DNA sequence was determined for one of the gene for the
      elongation factor 1 alpha (TEF), isolated from the zygomycete Absidia glauca.
      Sequence comparison with TEF genes from other fungi show the highest similarity
      to TEF-genes of the closely related zygomycete Mucor racemosus (Sundstrom et al.
      1987). Southern-blot analysis of genomic DNA from A. glauca with the TEF gene
      reveals six chromosomal copies in the genome. In transformation experiments of A.
      glauca, vector constructions were used which allow targeting of one of the TEF
      loci. Several transformants of A. glauca were analyzed at the DNA level. In most
      cases, rearranged forms of autonomously replicated plasmids could be found in
      these isolates. However, some transformants show a different restriction pattern
      of the TEF loci if compared with the parental strains. From Southern-blot data it
      could be concluded that in one case the rearrangement lies downstream of one TEF
      locus. In a second case genetic parts following the 3'-end of the TEF gene are
      moved towards the 5'-end of the gene.

PMID- 7735721
TI  - ECDC--a totally integrated and interactively usable genetic map of Escherichia
      coli K12.
AB  - A printed version of the interactively usable genetic map of Escherichia coli K12
      is provided together with some statistical information about the actual status of
      the respective genome sequencing project. A total of 3,179,967 bp corresponding
      to 68.38% of the genome is available through the ECDC database. Contigs as well
      as individual DNA sequences for each gene or open reading frame are provided.
      Access to a number of other databases is possible using World Wide Web or local
      programs.

PMID- 7735722
TI  - Moulds in containers with biological wastes.
AB  - The collection of biological wastes in separate bio-containers can lead to a
      favoured development of thermophilic and thermotolerant moulds, especially of
      mucoraceous species and aspergilli, among which the human pathogen A. fumigatus
      is especially frequent. The abundantly produced spores are released into the air
      and can evoke severe infections in persons with immune-deficiencies. In two
      series of experiments it was demonstrated that the following procedures can
      reduce the number of spores in the air in the bio-containers above the biological
      wastes: (1) wrapping the wastes in portions in newsprint: the number of colony
      forming units (CFU) decreases for about 50-70%; (2) cleaning of the container
      after each emptying with diluted vinegar: the number of CFU is reduced for up to
      80%; (3) placing the container at shady sites: the temperature of the air inside
      the bio-containers at shady sites is approximately 5-8 degrees C lower than at
      sunny places with the consequence that the number of CFU in the air above the
      biological wastes is decreased. Based on these results principles for the
      handling of biological wastes are set up.

PMID- 7735723
TI  - Cultivation of Salmonella in contact with epithelial cells.
AB  - An in vitro cultivation model for Salmonella having contact to epithelial cells
      was developed, which led to an increase in the production of toxic substances.
      The toxin assay on CHO-K1 cells was used for the determination of the toxic
      activities. Salmonella strains cultivated in contact with a monolayer of the
      intestinal cell line IEC-6 produced considerably more toxin than Salmonella
      strains cultivated on VERO cells. The toxin formed was heat-labile.

PMID- 7735724
TI  - Misplacing memory: the effect of television format on Holocaust remembrance.
AB  - The Simon Wiesenthal Center's Beit Hashoah Museum of Tolerance in Los Angeles
      provides a case study of how museum designers use television formats to
      communicate and educate. A dramatic spectacle is created that shapes how visitors
      are to feel and think. This spectacle turns the museum into an emotions factory
      and functions as a 'format of control'. It exerts a 'creeping surrealism' upon
      the visitor that misplaces memory and history by degrees. The implications of
      being unable to transcend television formats in a post-Gutenberg-galaxy world are
      discussed.

PMID- 7735725
TI  - The mirage of gender equality: occupational success in the labour market and
      within marriage.

PMID- 7735726
TI  - Serum soluble interleukin-2 receptor, soluble CD8 and soluble intercellular
      adhesion molecule-1 levels in Crohn's disease, celiac disease, and systemic lupus
      erythematosus.
AB  - We investigated soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8) and
      soluble intercellular adhesion molecule-1 (sICAM-1) levels in the sera of
      patients with non-malignant diseases believed to have an autoimmune or
      immunosuppressive component, Crohn's disease, celiac disease, and systemic lupus
      erythematosus (SLE). Sera of healthy blood donors served as controls. All samples
      were analyzed by commercial ELISA kits for sIL-2R, sCD8, and sICAM-1. Our control
      level of sIL-2R (x +/- S.D) was 395 +/- 84 units/ml, sCD8 (x +/- S.D.) 263 +/- 90
      units/ml and sICAM-1 405 +/- 118 ng/ml. The 8 Crohn's disease patients had an
      average sIL-2R level of 920 +/- 329 units/ml, and an average sCD8 level of 355 +/
      91 units/ml, and sICAM-1 952 +/- 329 ng/ml. The four celiac disease patients had
      an average sIL-2R concentration of 1740 +/- 1071 units/ml, a sCD8 level of 460 +/
      320 units/ml and sICAM-1 1221 +/- 720 ng/ml. The three systemic lupus
      erythematosus patients had an average sIL-2R of 1023 +/- 123 units/ml, and an
      average sCD8 of 395 +/- 69 units/ml, and sICAM-1 1153 +/- 219 ng/ml. Thus, sIL-2R
      and sICAM-1 were significantly elevated over control levels in all 3 patient
      groups, and sCD8 was mildly elevated. These results indicate enhanced immune
      activation which may be a common feature in the onset and/or progression of these
      idiopathic illnesses.

PMID- 7735727
TI  - Modulation of hepatic adrenergic receptor ontogeny by thyroid hormone.
AB  - During hepatic development, beta-adrenergic receptors are replaced by alpha 1
      receptors, an important event in the switchover from neonatal to adult glucose
      metabolism. In mature tissues, expression of adrenergic receptor subtypes is
      regulated, in part, by thyroid hormones; the current study examines whether they
      also participate in the transition of hepatic receptors. When triiodothyronine
      (T3) was given to rat pups on postnatal days 11-15, just before the receptor
      transition period, the developmental increase of alpha 1-receptors was
      accelerated but there was no change in the ontogenetic decline of beta-receptors.
      When propylthiouracil (PTU) was given over the same period to induce
      hypothyroidism, neither alpha 1- nor beta-receptor development were affected,
      thus, despite the selective promotion of alpha 1-receptor sites by exogenous
      thyroid hormone, endogenous hormone is not obligatory for receptor switching to
      take place. Finally, to distinguish whether the receptor transition is a function
      of general growth and cell differentiation, which are also impacted by thyroid
      status, animals were given PTU from gestational day 17 through postnatal day 5, a
      treatment that reproduces the growth defects of congenital cretinism, but that
      allows hormone levels to return to normal during the receptor transition period;
      the appropriate switchover still occurred. These studies indicate that thyroid
      hormone selectively promotes hepatic alpha 1-receptor expression during
      development, but is not itself responsible for the ontogenetic switchover in
      adrenergic receptor subtypes. Because other factors, such as glucocorticoids,
      have similar modulatory effects, the timing of hepatic adrenergic receptor
      development may be governed by multiple factors, no one of which is absolutely
      sufficient or essential.

PMID- 7735728
TI  - The cytoprotective effect of the immunomodulator AS101 against hydrochloride
      induced gastric lesions.
AB  - AS101 as a new immunomodulator has been shown to induce production of a variety
      of cytokines such as interleukin-1, interleukin-2, colony-stimulating factor,
      interferon-gamma and tumor necrosis factor, and demonstrate a potential chemo
      protection from chemotherapy induced immunosuppression and hematopoietic toxicity
      in tumor bearing mice and cancer patients on phase I and II clinical trials. This
      study was designed to verify whether AS101 exerts a cytoprotective effect in rats
      and mice with gastric lesions induced by intragastric (i.g.) instilling of 0.6N
      hydrochloride (HCl). AS101 given intraperitoniously (i.p) 2h before a HCl
      administration markedly prevented HCl-induced gastric lesions both in rats and
      mice. It also accelerated the ulcer repair when given i.p. 1h after a HCl
      treatment. Indomethacin (IND), a cyclo-oxygenase inhibitor, given i.p. at a non
      ulcerogenic dose of 5mg/kg 1h before AS101 administration, abolished its
      protective effect. Mechanistic analysis showed that the gastric cytoprotective
      property of AS101 appears to be mediated through the induction of prostaglandin
      E2 (PGE2) and epidermal growth factor (EGF), of which, both prevent the gastric
      mucosa from HCl ulceration while EGF also contributes to the promotion of ulcer
      repair. This study adds another cytoprotective property to the known
      immunomodulating role of AS101.

PMID- 7735729
TI  - Family support and coping with cancer: some determinants and adaptive correlates.
AB  - This paper studies the interrelationships between the coping behaviours of cancer
      patients and perceived amount and adequacy of family support, as well as the
      issue of how these predict psychosocial adjustment to cancer. Based on
      questionnaire data from a sample of 169 patients with cancers of various sites,
      three questions were considered in detail: (1) How might cognitive and
      behavioural modes of coping with cancer affect perceptions of support provided by
      one's family in terms of the amount as well as adequacy of various supportive
      acts? (2) Are coping modes to be considered when explaining inter-individual
      differences in perceived support adequacy, or can these differences be reduced to
      differences in amount of support? (3) Can distinct patterns of family support and
      coping preferences be identified and, if so, how do these patterns differ in
      indicators of psychosocial adjustment to cancer? Results suggest that cognitive
      strategies of coping may be more effective in 'mobilizing' family support than
      behavioural strategies. Moreover, the perceived adequacy of various support modes
      proves to be influenced by cognitive coping preferences independent of perceived
      amounts of support. Finally, results from cluster analyses point to a particular
      coping-support pattern identified as 'highly risky'. This pattern is
      characterized by generalized support deficits, strong tendencies towards
      rumination, and weak tendencies towards minimizing disease-related threat. The
      findings are discussed from an interactional perspective on support processes and
      with regard to implications for psychological intervention in cancer patients.

PMID- 7735730
TI  - Skin cancer attitudes: a cross-national comparison.
AB  - A questionnaire concerning attitudes towards skin cancer, sun exposure and
      general environmental issues was administered to 132 holiday-makers on a beach in
      south-west England and (in translation) to 142 visitors to another beach in north
      west Italy. Following the Janis & Mann (1977) classification of strategies for
      coping with decision conflicts, subscales were derived measuring tendencies to
      'avoid' thinking about environmental issues, to 'bolster' prior attitudes (by
      playing down the seriousness of the risk of skin cancer while attending to the
      pleasures of sunbathing), and to be 'vigilant' concerning risk information and
      the need for specific protective behaviour (e.g. sunscreen use). The British
      scored higher than the Italians, and women higher than men, on vigilance, but
      there were no gender or nationality differences on the other subscales considered
      as a whole. Responses were also related to the covariates of age and self
      reported vulnerability to sunburn. Those who showed less concern with
      environmental issues also tended to play down the risks of skin cancer and be
      less vigilant with regard to self-protection. It is suggested that health
      promotion should address both cultural norms concerning exposure to the sun and
      people's intuitive notions about their relative personal vulnerability.

PMID- 7735731
TI  - Delay in seeking a cancer diagnosis: delay stages and psychophysiological
      comparison processes.
AB  - Two analyses of patient delay in seeking a medical diagnosis are considered. In
      the first, a model of delay is presented. Specifically, delay is comprised of
      four stages (appraisal, illness, behavioural and scheduling delay intervals),
      each governed by a conceptually distinct set of decisional and appraisal
      processes beginning with the initial day that an unexplained symptom is detected
      to the day the individual appears before a physician. The second analysis is a
      social psychological one of the attributions individuals draw when relating their
      symptoms to their expectations and knowledge about physiological bodily
      processes. The eight principles of Psychophysiological Comparison Theory (PCT)
      provide the basis for clarifying the psychological processes of symptom
      interpretation and appraisal. Two studies were conducted with women seeking
      diagnostic evaluations for prevalent cancers: breast or gynaecological tumours.
      Regarding the delay model, results indicated that the delay intervals were
      independent (i.e. uncorrelated). Also, appraisal delay constituted the majority
      (at least 60 per cent) of the total delay. In the test of PCT, support was found
      across measures of symptoms, the context in which the symptoms arose, and the
      inferences people made about the symptoms.

PMID- 7735732
TI  - Social comparison as a mediator between health problems and subjective health
      evaluations.
AB  - The role of social comparison in mediating the relation between 'objective'
      health status and subjective health evaluations was examined. In a random
      population sample (N = 361) it was shown that health problems were related to
      psychological distress, which in turn induced a downward comparison process. This
      downward comparison resulted in a perception of being better off than others in a
      similar situation (relative evaluation). While both health problems and
      psychological distress had strong direct effects on general health evaluations,
      relative evaluations explained further significant variance. In addition, it was
      found that although women reported more psychological and physical problems than
      men, they engaged more often in downward comparison and consistently felt more
      than men did that their health was better than that of most others. No gender
      differences in general health evaluations were found. Interestingly, social
      comparison had a stronger impact on the general subjective well-being of women
      than of men.

PMID- 7735733
TI  - Physical illness stigma and social rejection.
AB  - We use the stigma of illness as a model for uncovering which dimensions of
      stigmas are critical for causing social rejection. Subjects responded to 'medical
      case histories' representing 66 illnesses, rating the illness on a variety of
      dimensions (e.g. contagious/not contagious, common/rare), and a measure of social
      rejection. Regression analysis revealed that two dimensions predicted rejection:
      the severity of the illness, and whether the illness was behaviourally caused
      (multiple R = .68). In a second experiment, subjects responded to a case history
      of a fictitious disease that was either mild or severe, and was either
      behaviourally caused or not. Behavioural causality and severity emerged as
      reliable, independent sources of rejection. Diseases perceived to be severe or
      under personal control are most likely to lead to social rejection.

PMID- 7735734
TI  - Work and family roles in relation to women's well-being: a longitudinal study.
AB  - Previous research on women has focused on the influence of the overall work- or
      family-role experiences rather than on the specific characteristics of each role.
      Using multidimensional measures of work- and family-role experiences, this study
      first examined (Time 1) the additive cumulative contributions of role experiences
      in the prediction of women's well-being (happiness and symptoms of psychological
      distress). While work overload significantly predicted distress at Time 2, none
      of the family-role variables were related to well-being. Second, as the sample
      was made up of two groups of women who differed in occupational status
      (secretaries and professional women), it was possible that the effects of
      overload on distress might be conditioned by occupational status. The group X
      overload interaction term was found to be highly significant (p < .007); high
      occupational status moderated the negative effects of work overload. By contrast,
      secretaries were adversely affected by work overload. These results are discussed
      in relation to the existing literature, with reference to women's work and family
      roles in relation to well-being, and the effects of occupational status on health
      outcomes.

PMID- 7735735
TI  - Anticipated affective reactions and prevention of AIDS.
AB  - Controlling the AIDs epidemic may depend largely upon health education aimed at
      adolescents. A number of approaches have been applied to human immunodeficiency
      virus (HIV) preventive behaviour in adolescents, including the health belief
      model (Becker, 1974), protection motivation theory (Rogers, 1983), and the theory
      of planned behaviour (Ajzen, 1985, 1991). Since sexual behaviour is heavily
      influenced by emotions, a possible shortcoming of these models is that little
      attention is given to affective processes. In this study we investigated the role
      of anticipated, post-behavioural, affective reactions to (un)safe sexual
      behaviours in the context of the theory of planned behaviour (TPB). The results
      showed that anticipated affective reactions such as worry and regret predicted
      behavioural expectations over and above the components of the TPB. The
      implications for our understanding of adolescent sexual behaviour and for
      campaigns aimed at the reduction of risky sexual practices will be discussed.

PMID- 7735736
TI  - The injurious effects produced by X-rays. 1916.

PMID- 7735737
TI  - Review article: current indications for high resolution computed tomography
      scanning of the lungs.
AB  - High resolution computed tomography (HRCT) is an effective technique for
      demonstrating the lung parenchyma in detail and overcomes many of the
      inadequacies of chest radiography in the diagnosis of diffuse lung disease. This
      article reviews the role of HRCT in the management of patients with chronic
      infiltrative lung disease, occupational lung disease, airways disease and acute
      and sub-acute lung disease.

PMID- 7735738
TI  - Intravascular ultrasound imaging of peripheral arteries as an adjunct to
      atherectomy: preliminary experience.
AB  - 12 atherosclerotic lesions in nine patients, including four restenoses after
      balloon angioplasty, were treated by atherectomy under the guidance of
      intravascular ultrasound (US). Echogenicities of the plaques and morphological
      alterations in the arterial walls produced by atherectomy were evaluated. The two
      layered appearance of post-angioplasty restenoses was found to be inner fibrous
      intimal thickening with proliferation of smooth muscle cells and outer residual
      collagen-rich plaque. The deep cut surfaces were shown as concave U-shaped
      defects. Medial tissues were present in all cases where intravascular US
      demonstrated the disruption of a thin hyperechoic layer of the internal elastic
      lamina. Intravascular US imaging may provide valuable information on the degree,
      eccentricity and histological type of stenosis, the presence of calcification
      before atherectomy, and on the extent of excision and the morphological changes
      in the arterial wall after atherectomy.

PMID- 7735739
TI  - Dual contrast magnetic resonance imaging with combined use of positive and
      negative contrast agent in human hepatocellular carcinoma.
AB  - Dual contrast magnetic resonance imaging (DCMR) with combined use of a negative
      contrast medium, chondroitin sulfate iron colloid (CSIC), and a positive contrast
      medium, Gd-DTPA, was attempted in 20 cases of hepatocellular carcinoma. Spin echo
      T1 weighted and T2 weighted images (T1WI, T2WI), and T1 weighted images 15 min
      after intravenous injection of Gd-DTPA (0.1 mmol kg-1) were obtained. Within 1
      week, these MR studies were repeated within 1 h of intravenous injection of CSIC
      (23.6 mumol Fe kg-1) under similar conditions. DCMR and the other five imaging
      techniques were visually evaluated and compared in terms of tumour detectability,
      tumour spread and qualification of tumours (depiction of inner structure). DCMR
      was significantly better than Gd-DTPA enhanced T1WI in tumour detectability, and
      better than Gd-DTPA enhanced T1WI or CSIC enhanced T1WI in depicting tumour
      spread. In the qualification of tumours, DCMR was significantly better than all
      the other five imaging techniques. None of the patients in this study showed
      adverse reactions or significant changes in biochemistry. DCMR is an imaging
      technique which is able to utilize the characteristics of these contrast agents
      collectively, and exhibits advantages in grasping the inner structure of tumours,
      especially in hepatocellular carcinoma.

PMID- 7735740
TI  - Magnetic resonance imaging in myelodysplastic syndromes.
AB  - In this study we used magnetic resonance imaging (MRI) to examine the axial bone
      marrow of 11 patients with myelodysplastic syndromes (MDS). T1 weighted images
      showed a reduction in signal intensity in all patients. The degree of reduction
      in signal intensity correlated with bone marrow cellularity rather than
      percentage blasts or French-American-British Co-operative group (FAB)
      classification. T2 weighted images showed an increase in signal intensity in 10
      out of 11 patients; however, reliable grading was not possible using this
      sequence. Both T1 and T2 weighted images indicated a homogeneous pattern of
      disease within the axial skeleton in MDS. We have also shown that iron deposition
      in multiply transfused patients is a significant factor influencing signal
      reduction. The results of this study suggest that MRI may have a diagnostic role
      in MDS but is unlikely to be of value in staging.

PMID- 7735742
TI  - Computed tomography evaluation of renal parenchymal volume in patients with
      chronic pyelonephritis and its relationship to glomerular filtration rate.
AB  - The measurement of renal parenchymal volume using a calibrated computed
      tomography image processing method has been evaluated clinically on a cohort of
      patients with chronic pyelonephritis. Comparison of renal volume with function as
      assessed by 99Tcm DTPA renography demonstrated a simple linear relationship in
      patients who were normotensive and aproteinuric. The implications of this result
      on the interpretation of prognostic factors determining declining renal function
      in chronic pyelonephritis are discussed.

PMID- 7735741
TI  - A blinded prospective trial of low-residue versus normal diet in preparation for
      barium enema.
AB  - This study was undertaken to determine whether the omission of a low-residue diet
      in the days leading up to barium enema resulted in poorer bowel preparation. 300
      patients were randomized prospectively into one of two groups. One group followed
      a low-residue diet for the 3 days leading up to the study, the other continued
      their usual diet. Both groups had two doses of "Picolax" the day before the
      study. 17 patients did not attend, and a further two patients were excluded,
      leaving 281 patients for prospective study. The subsequent investigation was
      assessed blind by a consultant radiologist and graded for faecal residue, mucosal
      coating and diagnostic quality. No statistically significant difference was found
      between the two groups for amount of faecal residue (p < 0.25), mucosal coating
      (p < 0.25) or diagnostic quality (p < 0.5). We conclude, therefore, that a
      preliminary low-residue diet is unnecessary in the preparation of patients for
      barium enema. Patients should continue with their usual diet up to the day prior
      to the test and then have standard purgative preparation.

PMID- 7735743
TI  - Off-resonance binomial composite pulses in 2D and 3D fat/water imaging at 0.5 T.
AB  - A new method of acquiring two-dimensional (2D) and three-dimensional (3D)
      fat/water decomposed images on a 0.5 T magnetic resonance (MR) imaging system is
      described. The method uses a gradient-recalled echo (GRE) sequence incorporating
      a composite 121 pulse, originally used for magnetization transfer contrast (MTC)
      experiments, for frequency-selective pre-saturation. By applying the 121 pulse
      off resonance, a sharp discrimination between the chemically shifted water and
      fat signals may be obtained using a composite pulse as short as 4 ms. Phantom
      studies demonstrate that suppression ratios as high as 50:1 are achievable. The
      new method has been applied to volunteers and patients, and good fat/water images
      of limb, abdomen, head and neck obtained. The new method can be incorporated into
      other pulse sequences related to GRE, such as phase contrast (PC) and time-of
      flight (TOF), and represents the first practical (i.e. rapid) method for 3D
      fat/water imaging at an operating field as low as 0.5 T.

PMID- 7735744
TI  - MBS: a model for risk benefit analysis of breast cancer screening.
AB  - Breast cancer screening programmes employing mammography are being implemented in
      various European countries. Different screening protocols are used in
      demonstration projects and nationwide programmes. To evaluate and improve
      protocols, a computer model for the evaluation of breast cancer screening has
      been developed. The availability of such a model can be of great importance in
      obtaining a better insight into the influence of various parameters. The Monte
      Carlo computer model is based on random selection from distributions of relevant
      parameters including tumour onset, tumour growth rate, lifetime expectancy,
      tumour detection size for screening and spontaneous observation. The radiation
      risk is calculated for various screening protocols employing multiplicative and
      additive risk models combined with lifetime expectancy, number of females
      screened and absorbed dose per screening session. The benefit is calculated on
      the basis of the reduction in tumour size at detection due to screening compared
      with spontaneous observation and the survival as a function of tumour diameter.
      Data from the Swedish two-county study are used to validate the model in terms of
      prevalence, interval tumour rates and interval tumour diameter distributions.
      Except for the spontaneous tumour diameter distribution, the model can describe
      the Swedish two-county study. Specific information is presented on the
      distributions of relevant parameters.

PMID- 7735745
TI  - Classification of ductal carcinoma in situ by image analysis of calcifications
      from digital mammograms.
AB  - There is evidence to suggest that non-comedo cases of ductal carcinoma in situ
      (DCIS) may have a lower risk of progressing to invasive disease than comedo DCIS
      and may be managed with less radical treatment. Most cases of DCIS present as
      calcifications on the mammogram and, due to differences in the tumour
      architecture, comedo calcifications often have a characteristic linear or
      branching appearance. In this study, computer methods were developed to identify
      the comedo cases using the imaging features of individual calcifications and of
      calcification clusters. Classifier performance was measured using the area under
      the receiver operating characteristic (ROC) curve and was optimized by systematic
      testing of many different combinations of these features. On a test-set of 42
      cases the computer achieved a ROC curve area of 0.91 using six combined cluster
      features. These results are encouraging given the observed overlap in appearance
      between the comedo and non-comedo cases.

PMID- 7735746
TI  - Subjective evaluation of image quality based on images obtained with a breast
      tissue phantom: comparison with a conventional image quality phantom.
AB  - A breast tissue phantom was used for assessment of mammographic image quality.
      Three images, exposed to give a reference area film density of 1.25 +/- 0.03,
      were obtained for each of five different film/kV combinations. Each of three
      radiologists carried out a series of three blind readings, in which the 15 films
      were ranked according to sharpness and contrast. In a similar experiment with a
      conventional image quality phantom, scores for the visualization of simulated
      calcifications and contrast-detail performance, and measures for resolution and
      contrast were obtained. In both experiments, the judgements of the readers were
      highly consistent, and both the intraobserver and interobserver variabilities
      were non-significant. No significant differences between the film/kV combinations
      were found with respect to high-contrast resolution and visualization of the
      simulated calcifications. The contrast measures obtained with the conventional
      phantom correlated well with the contrast scores obtained with the breast tissue
      phantom. The contrast-detail scores obtained with the conventional phantom showed
      no correlation with the scores obtained with the breast tissue phantom, nor with
      the contrast measures obtained with the conventional phantom.

PMID- 7735747
TI  - Radiotherapy portal verification: an observer study.
AB  - In many radiotherapy facilities radiotherapy portal verification is currently a
      subjective process based on the visual comparison of a treatment or portal image
      with a prescription or simulation image. The reliability of this process is
      unknown. We describe here a study in which 16 observers (oncologists, physicists
      and therapists) independently evaluated the geometric accuracy of 530 treatment
      fields on 45 patients. The treatment images were acquired by the BEAMVIEW on-line
      portal imaging system (Siemens Medical Laboratories, Concord, CA, USA).
      Illustrative examples of the large variation in observers' assessments of the
      same field are given. The kappa statistic is used to evaluate the degree of
      agreement between observers and between on-line (at the treatment unit) and off
      line (in a quiet viewing room) assessments. The best interobserver agreement was
      between the four oncologists contributing to the study although this level of
      agreement was rated only as "fair". Comparison of on-line and off-line decisions
      made by therapists exhibited "poor" agreement. This study has provided
      statistical confirmation of the suspicions of many workers in the field of
      radiotherapy portal verification, viz that the subjective evaluation of field
      accuracy is unreliable. However, the degree of unreliability is surprisingly
      large. The inconsistencies between observers documented in this study need to be
      clearly acknowledged in the development of protocols for the clinical use of on
      line portal imaging systems. Acceptable reliability in radiotherapy portal
      verification will only be achieved when subjective decision making is eliminated.

PMID- 7735748
TI  - Improved image quality utilizing dual plate computed radiography.
AB  - A method of improving image quality in computed radiography (CR) using dual plate
      exposure has been developed. Two CR image plates are used to increase the
      fraction of X-ray quanta absorbed from the beam. Spatial registration and
      combination of images from the two plates leads to an image with improved signal
      to-noise ratio characteristics. A cross correlation technique is used to register
      spatially the images from the front and rear plates. The modulation transfer
      function and noise power spectrum were measured for the single plate and combined
      dual plate images. Results indicate a potential increase of approximately 60% in
      the detective quantum efficiency (DQE) of the dual plate combined image compared
      with the single plate image. The improvement of DQE at high spatial frequencies
      is dependent on the accuracy of the registration of the two images. The actual
      improvement in imaging performance was measured using a contrast detail test
      piece. A computerized method was used to measure the imaged detail signal-to
      noise ratio of the details of different dimension. Results indicate an
      improvement of 21% in the signal-to-noise ratio of the details imaged with the
      dual plate arrangement compared with the single plate. This indicates that this
      technique can result in a significant increase in image quality for the same
      exposure level. Alternatively this technique could allow reduction in exposure
      while maintaining the same image quality achievable with the single plate system.

PMID- 7735749
TI  - Technical note: measuring the coracoclavicular distance with ultrasound--a new
      technique.
AB  - The distance between the clavicle and the coracoid process of the scapula is
      frequently assessed during the radiographic investigation of the
      acromioclavicular joint. This study defines an ultrasound technique (5 MHz real
      time linear array) for measuring the coracoclavicular distance, and determines
      its reliability and validity. A new ultrasonic technique was performed on 49
      healthy subjects who had volunteered to participate in the study, having given
      signed, informed consent. The measuring endpoints for the coracoclavicular
      distance were the superior border of the clavicle and the superior border of the
      coracoid process. Three replicate scans were performed on each shoulder. The
      ultrasound measurements for 19 of the subjects were compared with the measurement
      obtained from a normal shoulder radiograph (which had previously been requested
      on clinical grounds). The data were subjected to analysis of variance (ANOVA) and
      the limits of agreement method of analysis. The mean difference between the
      radiograph and ultrasound measurements was 0.38 mm. The limits of agreement (95%
      confidence intervals) were -0.57 (-0.97, -0.17) and 1.33 (0.93, 1.73).
      Intraoperator and interoperator reliability were evaluated with a multifactor
      ANOVA and gave p = 0.7 for intraoperator reliability and p = 0.5 for
      interoperator reliability. The mean of the coefficients of variation for the two
      operators was 1.84%. The average range for repeated trials (same operator, same
      subject) was 1.35 mm. The maximum differences in the averages for each operator
      was 1.2 mm. The ultrasound technique described is a reliable, accurate and valid
      technique for evaluating the coracoclavicular distance and may usefully
      supplement the routine radiographic examination of the shoulder in patients
      presenting for radiographic examination of the acromioclavicular joint.

PMID- 7735750
TI  - Technical note: perspex blocks for estimation of dose to a standard breast-
      effect of variation in block thickness.
AB  - Mean glandular dose in mammography may be deduced from measurements made using
      Perspex blocks. This method is almost universally used in the National Health
      Service Breast Screening Programme. The effect on the estimated mean glandular
      dose of variations in the measured thickness of Perspex from a nominal thickness
      of 40 mm was investigated. Results are presented from three UK Regions.
      Variations in measured Perspex thicknesses ranged from almost 8% below to about
      2% above the 40 mm nominal, causing errors in dose estimation, if uncorrected, of
      about +20% to -6.5%. A means of correcting dose estimates for measured
      differences in block thickness is presented. An alternative method of ensuring
      consistent dosimetry would be to use accurately machined Perspex blocks.

PMID- 7735751
TI  - Case report: lipoma arborescens of the sub-deltoid bursa.
AB  - Lipoma arborescens is a rare synovial disorder which principally affects the knee
      joint. We describe an unusual case of lipoma arborescens arising within the sub
      deltoid bursa in association with a rotator cuff tear. Pre-operative diagnosis
      was made by magnetic resonance imaging.

PMID- 7735752
TI  - Case report: the effect of contrast density on computed tomographic arterial
      portography.
AB  - Artifacts associated with computed tomographic arterial tomography (CTAP) are
      well documented. We report a patient undergoing CTAP in whom laminar flow
      artifact occurred using Iopamidol 370 mg ml-1 but not when using Iopamidol 300 mg
      ml-1 under identical conditions. The denser Iopamidol 370 mg ml-1 mixed
      inadequately with unopacified blood in the portal vein. This was not a problem
      with the less dense Iopamidol 300 mg ml-1 which is likely to be a more reliable
      contrast agent for CTAP.

PMID- 7735753
TI  - Case report: giant pararectal varices--computed tomographic appearances.
AB  - Computed tomography (CT) accurately identifies the presence of paraoesophageal,
      upper abdominal and anterior abdominal wall varices in portal hypertension. We
      present a case of giant pararectal varices and describe the value of dynamic
      contrast-enhanced CT in reliably establishing the nature of these structures.

PMID- 7735754
TI  - Case report: epidermoid cyst of the floor of the mouth: diagnostic imaging by
      sonography, computed tomography and magnetic resonance imaging.
AB  - Epidermoid and dermoid cysts are rare benign tumours which may occur anywhere in
      the body. About 7% of them are found in the head and neck region and only 1.6%
      are located within the oral cavity. Pre-operative imaging of these lesions
      provides important diagnostic and anatomical information with regard to the
      patient's therapeutic management. This case report describes imaging findings in
      a patient with an extensive epidermoid cyst located within the sublingual space.

PMID- 7735755
TI  - Case report: paediatric intramuscular haemangiomata--don't overlook the
      phlebolith!
AB  - Three children presented with soft tissue masses which were clinically suspected
      to be soft tissue sarcomas. The identification of phleboliths on initial
      radiological studies should have suggested the correct diagnosis of benign
      intramuscular haemangiomata. Subsequent referral to a paediatric oncological
      unit, and the unnecessary parental anxiety so generated, could have been avoided.

PMID- 7735756
TI  - Case of the month: inside a thin man--an engrossing problem.

PMID- 7735757
TI  - Radiation dose to the lens from CT brain scans in general radiology departments.

PMID- 7735758
TI  - A simple technique to reduce breast irradiation.

PMID- 7735759
TI  - Caesium-137 spherical sources for the LDR/MDR Selectron.

PMID- 7735760
TI  - Neoplasms of the lungs and bronchi. 1925.

PMID- 7735761
TI  - Invited review: biophysical properties and clinical applications of magnetic
      resonance imaging contrast agents.
AB  - Contrast enhanced magnetic resonance imaging (MRI) is a very versatile and
      effective technique for detecting and characterizing lesions, for identifying a
      variety of patho-physiological abnormalities, and for providing perfusion and
      functional information. The application of contrast enhanced MRI to many clinical
      and research indications has emerged because of the rapid evolution in imaging
      techniques, improved methodology, and the development of efficient and specific
      contrast agents. Problems related to optimizing parameters and dosage have been
      due to complex interplay of relaxation times, biophysical mechanisms and
      acquisition parameters. A knowledge of basic biophysical aspects is therefore
      essential for a full understanding of the results obtained for different organs
      under different conditions, and for optimizing the image parameters and dosage of
      contrast agents. This article underlines the biophysical basis of the effects of
      contrast agents in MRI, identifies the problems involved in optimizing the
      parameters for maximum efficiency, and presents a general overview of the
      clinical studies and research applications in the central nervous system,
      perfusion abnormalities, hepatobiliary system, musculoskeletal system and the
      gastrointestinal tract. The section on perfusion studies includes a discussion of
      quantitative analysis and kinetic models describing the effects of contrast
      agents. Finally, a critical evaluation of the scope and limitations of contrast
      enhanced MRI is presented.

PMID- 7735762
TI  - Chest radiograph appearance at 24 h of age--prediction of chronic oxygen
      dependency.
AB  - Chronic oxygen dependence is associated with immaturity, male sex and low
      birthweight, but amongst that high risk group further criteria are necessary to
      predict those most at risk. We previously developed a chest radiograph scoring
      system which, when used at 1 month of age, proved useful in predicting chronic
      oxygen dependency at 36 weeks post-conceptional age (PCA). We have now assessed
      whether the scoring system, if applied at 24 h of age, added predictive value to
      readily available demographic and ventilatory data. 50 infants, birthweight less
      than 1200 g and ventilated from birth, were examined. They had a median
      gestational age of 27 weeks (range 23-34), birthweight of 886 g (range 470-1172)
      and chest radiograph score of 7 (range 2-13). Univariate analysis revealed that
      oxygen dependency at 28 days and 36 weeks PCA was significantly associated with
      low gestational age, male sex and high ventilatory requirements, in addition to a
      high chest radiograph score. Stepwise regression analysis, however, demonstrated
      that a high chest radiograph score predicted oxygen dependence at 28 days,
      independent of immaturity, low birthweight, male sex and high ventilatory
      requirements. A chest radiograph score of more than 5 rendered an infant four
      times more likely to be oxygen dependent at 28 days than those with lower scores.
      We conclude the chest radiograph appearance at 24 h of age could be used as a
      criterion to institute interventional strategies aimed at reducing chronic oxygen
      dependence.

PMID- 7735763
TI  - Default display arrangements of images on PACS monitors.
AB  - Our hospital is currently installing one of the largest non-military hospital
      wide picture archiving and communications systems (PACS) in the world [1, 2]. We
      are designing default modes for the display of images on PACS workstation
      monitors so that these can be implemented in future software releases. In this
      article we present the considerations and reasoning influencing our decisions
      upon how best to arrange and present the images from the various radiological
      modalities for ease of soft copy reporting.

PMID- 7735764
TI  - High resolution T1 weighted magnetic resonance imaging of the deep brain
      structures using a reduced bandwidth.
AB  - High spatial resolution T1 weighted images of the brain were acquired in 5-13 min
      on a whole-body magnetic resonance imager operating at 1.5 T. In order to obtain
      5-8 cm field of view images, the receiver bandwidth (Bw) was lowered to 2 kHz.
      The use of a 2 kHz Bw, instead of the standard 16 kHz Bw, partially compensated
      the signal loss due to the small pixel size by increasing the signal-to-noise
      ratio, without scan time penalty. The chemical shift artifact associated with
      reduced Bw was not observed because fat signal is negligible in the brain.

PMID- 7735765
TI  - Cervical lymphadenopathy: ratio of long- to short-axis diameter as a predictor of
      malignancy.
AB  - The purpose of this study was to evaluate short- and long-axis diameters of
      enlarged cervical lymph nodes with ultrasonography and to determine whether the
      long-to-short axis (l/s) ratio is a valid diagnostic parameter in the
      differentiation between benign and malignant nodal disease. 730 enlarged cervical
      lymph nodes in 285 patients were examined with ultrasound. The short- and the
      long-axis diameters of each enlarged node were measured and the l/s ratio
      calculated. Definite diagnoses of the nodes were obtained by histological
      examination following neck dissection. 95% of enlarged cervical nodes shown on
      ultrasound to have a l/s ratio of more than 2 were correctly diagnosed as benign.
      Nodes presenting with a more circular shape and a l/s ratio of less than 2 were
      diagnosed correctly as metastases with 95% accuracy. The l/s ratio of lymph nodes
      thus provides an excellent criterion for differentiation between benign and
      malignant enlargement in cervical lymphadenopathy.

PMID- 7735766
TI  - Ultrasound-guided percutaneous fine needle puncture of the gallbladder for
      studies of bile composition.
AB  - Ultrasound-guided percutaneous fine needle puncture of the gallbladder (PFNP-GB)
      is invaluable for diagnostic and research purposes, but there are few reports
      about its safety. We therefore describe the efficacy and side-effects of 43
      consecutive gallbladder punctures in 39 patients. PFNP-GB was successful in 40/43
      (93%), but failed in three. Bile was completely aspirated in 28 of the 40 (70%)
      successful procedures. After 36 of the 43 punctures (84%), the patients remained
      asymptomatic, although on seven occasions (16%) the patients complained of right
      upper quadrant pain 0.5-12 h after the procedure. In six of these, the pain
      resolved in 2-24 h, although one developed a leucocytosis (22 x 10(9) 1(-1)). The
      seventh patient developed pyrexia and signs of generalized peritonism, which
      settled with conservative therapy. Ultrasonographic abnormalities of the
      gallbladder wall were seen in five of the seven symptomatic patients, consisting
      of: (i) an increase in the thickness of the gallbladder wall (n = 5) from less
      than 2 mm to 4-14 mm; (ii) peri-cholecystic collections (n = 2) measuring 5 and
      11 mm in diameter; (iii) an intraluminal mucosal flap (n = 1); (iv) an
      intraluminal echogenic layer (n = 1); and (v) a 12 cm intraabdominal haematoma in
      the patient with generalized peritonism. Predictors of pain were: (i) the number
      of needle "passes" (3.7 +/- 0.8, range 2-8, in patients with pain vs 2.0 +/- 0.2,
      range 1-6, in pain-free patients, p < 0.02); (ii) the absence of gallbladder
      stones (p < 0.03); and (iii) incomplete aspiration of bile from the gallbladder
      (p < 0.02). PFNP-GB is an effective way of sampling fresh gallbladder bile,
      although there is a 16% risk of inducing pain and/or ultrasonographic changes in
      the gallbladder.

PMID- 7735767
TI  - The use of a contrast-detail test object in the optimization of optical density
      in mammography.
AB  - In mammography, it is important that the maximum amount of diagnostic information
      is obtained from each radiograph. One of the factors influencing image quality is
      the optical density of the film. In this study, a contrast-detail test object was
      used to establish the optimum optical density value on the basis of signal-to
      noise ratio (SNR) for two mammographic film-screen combinations under particular
      processing conditions. The optimum optical density, taken as being the point at
      which the threshold contrast is a minimum varied little with detail size. The
      optimum optical density for the Fuji film-screen combination with Photosol
      chemistry was found to be higher than that for the Kodak film-screen combination
      and Kodak processing conditions studied. Although the actual values of optical
      density are specific to the fixed processing conditions encountered, the
      technique has more general applicability.

PMID- 7735768
TI  - The role of flow cytometry in non-resected cervical carcinoma.
AB  - Flow cytometry (FCM) has a prognostic value for many malignant neoplasms in terms
      of treatment response rate and survival. However, its role in non-resected
      cervical carcinoma remains uncertain. We have collected 96 paraffin-embedded
      specimens taken from non-resected cervical cancer patients treated by
      radiotherapy (RT) alone between 1984 and 1986. Our data revealed that FCM has
      little correlation with patients' age, pathological grade and clinical stage.
      Ploidy pattern and clinical stage correlate significantly with complete remission
      (CR) rate (p = 0.001 and 0.03). Most diploid or low-stage tumours (IB to IIA)
      obtained CR after RT alone. The application of an intravaginal extension electron
      cone (IVEC) (p = 0.019) and CR status (p = 0.0001) yield significant better
      overall survival (OS) rates than their alternative groups. The Cox regression
      model has confirmed these two variables as having an independent influence on OS.
      We thus conclude that both ploidy pattern and S-phase fraction (SPF) predict
      neither pre-treatment biological behaviour of the tumours nor overall survival.
      However, ploidy pattern has an independent influence on CR rate.

PMID- 7735769
TI  - Radiation doses to paediatric patients undergoing micturating cystourethrography
      examinations and potential reduction by radiation protection optimization.
AB  - Dose-area product values were measured in paediatric micturating
      cystourethrography examinations in two dedicated facilities. The results are
      compared, taking into account features of the X-ray rooms and differences in
      examination protocol. Several optimization procedures were simulated or
      implemented, in order to estimate the dose savings which could be attained.
      Potential savings identified in the dose-area values reach about 85% for both
      centres.

PMID- 7735770
TI  - Radiation dose reduction in paediatric fluoroscopy using added filtration.
AB  - Studies on a water phantom indicate that the insertion of extra tube filtration
      combined with the removal of the antiscatter grid can reduce the total energy
      imparted from paediatric fluoroscopy by a factor of more than four when automatic
      exposure control is used. The omission of the grid is responsible for up to 40%
      of the reduction while the addition of 0.7 mm steel filtration is found to
      account for a further reduction in energy imparted of between 57% and 70%, for
      depths of water simulating small patients of 6-16 cm thickness. For all contrast
      paediatric examinations the reduction in image quality was considered to be small
      and the diagnostic information unimpaired with the filter in place.

PMID- 7735771
TI  - The radiation exposure of the patient from stable-xenon computed tomography.
AB  - For stable-xenon computed tomography (CT), an X-ray examination for measurement
      of cerebral blood circulation in the brain, the radiation exposure of the patient
      was determined in order to estimate the risk of inducing cancer. Organ doses of
      brain, eyelenses, thyroid and gonads have been calculated using the measured air
      kerma free-in-air on the axis of rotation and organ-specific conversion factors
      calculated with the Monte Carlo method. Dose measurements with TLD-100 rods using
      a humanoid Alderson phantom were carried out for verification of the calculated
      organ doses. In the case of brain partially located in the region of primary
      radiation a mean organ dose of 39 mSv was calculated. The dose measurements
      showed dose equivalents between 6 and 68 mSv in different regions of the brain
      and consequently an inhomogeneous dose distribution. From an estimation of the
      radiation-induced risk using the effective dose of 1.6 mSv it follows that one
      additional fatal cancer per 12,500 stable-xenon CT examinations has to be
      expected. The organ doses of eyelenses and thyroid located in the region of
      scattered radiation are so low that biological effects are hardly to be expected.
      The calculated dose equivalents of 6.5 mSv and 0.5 mSv, respectively, are in good
      agreement with measurements. The organ dose of gonads amounted to less than 0.07
      mSv.

PMID- 7735772
TI  - Technical note: identifying and aspirating hip effusions.
AB  - Ultrasound has become a routine investigation in the investigation of the painful
      hip in children. It has been recommended that all effusions demonstrated by
      sonography be drained. Based on the experience of 800 hip aspirations, the
      authors describe an approach to the demonstration and aspiration of hip effusions
      with some of the pitfalls that result in false positive and false negative
      diagnoses.

PMID- 7735773
TI  - Technical note: a survey of the illumination from diagnostic X-ray light-beam
      diaphragm systems.
AB  - UK radiation protection legislation requires, where applicable, the fitting of
      light-beam diaphragm systems to diagnostic radiographic X-ray equipment.
      Measurements performed as part of a quality assurance programme showed that the
      level of illumination from equipment varied considerably. We decided to include a
      measurement of the illumination of light-beam systems as a routine part of our
      programme. The standard method used involved measuring the average illumination
      at 100 cm focus to field distance for a 25 x 25 cm light field. The results of
      initial measurements for 73 individual systems (44 fixed, 29 mobile) demonstrate
      a considerable range in levels with the ratio of maximum to minimum values being
      approximately 16. Mean values are 130 lux (all systems), 123 lux (fixed systems)
      and 141 lux (mobile systems). Comparisons are made with the limiting values
      specified by the Department of Health for mammographic X-ray equipment for breast
      screening and for new General Electric equipment. A local limiting value of 100
      lux is proposed for routine testing purposes.

PMID- 7735774
TI  - Case report: inferior vena caval thrombosis following severe liver trauma and
      perihepatic packing--early detection by intraoperative ultrasonography enabling
      treatment by percutaneous mechanical thrombectomy.
AB  - Patients with severe liver trauma present a major challenge in management. We
      report the successful treatment of a patient presenting with a severe liver
      injury. The detection of major inferior vena caval thrombosis by intraoperative
      ultrasonography enabled the use of a percutaneous thrombectomy device to
      facilitate dissolution of the thrombus.

PMID- 7735775
TI  - Case report: diffuse fatty infiltration of the renal parenchyma secondary to
      bilateral angiomyolipomas--features on ultrasound and computed tomography.
AB  - A case is described where ultrasound demonstrated diffusely increased
      echogenicity in massively enlarged kidneys. Computed tomography confirmed fatty
      replacement of the renal parenchyma, allowing a confident diagnosis of multiple
      bilateral angiomyolipomas in a clinical setting of tuberous sclerosis. This is
      the first ultrasound demonstration of such diffusely echogenic kidneys in
      angiomyolipoma.

PMID- 7735776
TI  - Case report: inflammatory abdominal aortic aneurysm--dynamic Gd-DTPA enhanced
      magnetic resonance imaging features.
AB  - Inflammatory abdominal aortic aneurysm is an uncommon disorder characterized by
      marked thickening and extensive inflammatory changes of the aneurysmal wall. The
      appearances of an inflammatory abdominal aortic aneurysm on dynamic Gd-DTPA
      enhanced magnetic resonance imaging are described and the value of this modality
      in achieving a pre-operative diagnosis is emphasized.

PMID- 7735777
TI  - Case report: annular pancreas divisum--a report of two cases and review of the
      literature.
AB  - Annular pancreas divisum is a rare congenital variant of pancreatic anatomy which
      may cause symptoms of gastric outlet obstruction and recurrent pancreatitis. It
      is diagnosed by endoscopic retrograde pancreatography. We present two cases of
      this condition and review the literature.

PMID- 7735778
TI  - Case of the month: pseudo-pseudo-obstruction.

PMID- 7735779
TI  - Short communication: normal tissue injury after cancer therapy is a local
      response exacerbated by an endocrine effect of TGF beta.
AB  - The sensitivity of normal tissues rather than of the tumour usually limits the
      effectiveness of cancer treatment. The normal tissue side effects from
      chemotherapy and/or radiotherapy result from both direct cellular loss and the
      extensive fibrosis that develops at the site of injury. Recent evidence suggests
      that the cytokine, transforming growth factor beta (TGF beta), mediates this
      fibrogenic process. Herein, we provide evidence in support of the hypothesis that
      the fibrosis formation following therapy results not only from TGF beta produced
      locally in the injured normal tissue, but also from circulating TGF beta released
      by the tumour. Thus, therapy-induced normal tissue damage appears in part to be a
      local manifestation of a systemic condition.

PMID- 7735780
TI  - Prolonged contrast enhancement of the inner ear on MRI in Ramsay Hunt syndrome.

PMID- 7735781
TI  - Oysters, Crasostrea gigas, as the second intermediate host of Gymnophalloides
      seoi (Gymnophallidae).
AB  - Gymnophalloides seoi has drawn medical attentions since the discovery of the
      first human case and a highly endemic area on a southwestern coastal island of
      Shinangun, Korea. Marine bivalves especially oysters were strongly suspected as
      the source of infection. In this study the oysters, Crassostrea gigas, naturally
      produced from the endemic area were examined whether they contain gymnophallid
      metacercariae. All of 50 oysters examined were infected with the metacercariae of
      a gymnophallid, with the metacercarial density per oyster of 610 on average (2-4,
      792 in range). Later they were identified as G. seoi by obtaining adult worms
      from experimental mice. The metacercariae were unencysted, and firmly attached on
      the mantle surface of the oysters with their oral sucker. In sectioned specimens
      they were equipped with the ventral pit, a peculiar organ of the genus
      Gymnophalloides, and non-muscular genital pore which was connected dorsally to
      the seminal vesicle. The seminal vesicle was in a great majority mono-sac. By
      this study, it has been confirmed that the oyster is a 2nd intermediate host of
      G. seoi as well as the major source of human infection with this fluke.

PMID- 7735782
TI  - [Seasonal prevalence and behaviour of Aedes togoi].
AB  - Ecological studies of Aedes togoi, the vector of malayan filariasis, were carried
      out at Tolsando, Yosu and Sokcho area in 1991. The adult population of Aedes
      togoi was continuously appeared from the first week of April to the end of
      November showing the highest density in July. The larvae of Aedes togoi were
      found at rock pools from March to December in Sokcho area and the density was
      highest in July and August, whereas in the southern coastal area (Yosu), the
      larvae were found throughout the year and the density was the highest in June.
      The rate of larvae inhabited below 0.5% salinity was 45.7% in Sokcho and 51.7% in
      Yosu. The feeding activity of Aedes togoi was nocturnal, with the peak period of
      01:00-03:00 hours. Indoor feeding activities were slightly higher than outdoors
      showing the biting ratio of 1:0.8 (indoor: outdoor). The average number of Aedes
      togoi attracted to CO2 gas was 8.5 whereas 117 Anopheles sinensis was attracted.
      The result indicates that CO2 is not an effective attractant for host seeking of
      Aedes togoi compared to Anopheles sinensis. The most common place was bedroom
      with 54.5% of total collections and next to stock place (18.2%), floor (9.1%) and
      kitchen (9.1%).

PMID- 7735783
TI  - Comparative epidemiological studies on vector/reservoir animals of tsutsugamushi
      disease between high and low endemic areas in Korea.
AB  - Comparative epidemiological studies on vector reservoir animals of tsutsugamushi
      disease were carried out in between south coast (the highest endemic) areas and
      east coast (low endemic) areas in October 1993. Fauna of field rodents and their
      population densities were not different between two areas. Antibody positive rate
      of Apodemus agrarius sera was higher in east coast (43.2% in south coast and
      63.6% in east coast). High correlation (r = 0.87) was shown between antibody
      positive rate of A. agrarius sera and population density of the vector mites
      (Leptotrombidium scutellare and L. pallidum). L. scutellare was predominant in
      south coast, showing 110.6 chigger index (74.9% of the total chiggers), whereas
      L. pallidum was predominant in east coast, showing 126.3 chigger index (60.4% of
      the total). As higher population density of L. scutellare was found in south
      coast where the prevalence rate of tsutsugamushi disease is the highest, it is
      believed that L. scutellare is more important vector species than L. pallidum,
      which may result from more frequent vector-human contact.

PMID- 7735784
TI  - The effect of reinfection with Neodiplostomum seoulensis on the histopathology
      and activities of brush border membrane bound enzymes in the rat small intestine.
AB  - Neodiplostomum seoulensis, one of the human intestinal trematodes, was reinfected
      to albino rats, and worm recovery rates, histopathology and activity changes of
      the intestinal brush border membrane bound enzymes were observed. The
      experimental groups were three; uninfected, primary infection and reinfection.
      The worm recovery rate in the reinfection group was much lower than in the
      primary infection group 14 days after infection. The duodenal histopathology
      showed villous atrophy during the first and second week in the primary infection
      group. In the reinfection group, however, villous changes occurred as early as 3
      days after the infection, and the lesion was found healed 7 days after infection.
      The activities of alkaline phosphatase and sucrase in the duodenum of primary
      infection rats decreased nearly half of the controls 2 weeks after infection,
      whereas the activities were unchanged in the reinfection group. However, no
      changes in the activities were observed in the proximal jejunum between the
      experimental groups. These findings suggested that a secondary infection of N.
      seoulensis in rats should make less damage on the intestinal mucosa than a
      primary infection.

PMID- 7735785
TI  - Oocyst production and immunogenicity of Cryptosporidium baileyi in chickens and
      mallards.
AB  - Two-day-old chickens and mallards were orally inoculated with one of 5 doses
      varying from 2 x 10(2) to 2 x 10(6) of C. baileyi oocysts per individual.
      Generally, the more oocysts inoculated were, the longer the patent periods were,
      and the more oocysts shedding were. Meanwhile increasing the inoculative dose,
      the prepatent periods were shortened except that mallards inoculated with 2 x
      10(2) and 2 x 10(3) oocysts failed to produce the oocysts. The more parasites
      involving oocysts appeared from the chicken in comparison to the mallard. In the
      chickens challenged with a single dose of 2 x 10(6) oocysts, a small number of
      oocysts were detected from feces on days 4-14 after challenge infection (ACI) in
      all of carrageenan administered groups and in the control groups inoculated with
      2 x 10(2) and 2 x 10(3) oocysts. In the mallards, a few oocysts were also
      recognized on days 5-15 ACI in all of carrageenan treated groups and in the
      control groups inoculated with 2 x 10(2), 2 x 10(3) and 2 x 10(4) oocysts. Just
      prior to challenge infection, phagocytic activity of peritoneal macrophages (Mo)
      and the number of peripheral Mo in both birds were significantly decreased in the
      carrageenan treated groups as compared to the control groups. Mild challenge
      infection in both birds denoted that the immunogenicity of C. baileyi to the
      birds was very strong, despite Mo blocker carrageenan administration.

PMID- 7735786
TI  - IgA response in mice infected with Neodiplostomum seoulensis.
AB  - To observe the production of IgA in Balb/c mice with neodiplostomiasis, 20 mice
      were infected with each 200 metacercariae of Neodiplostomum seoulenis. Sera and
      the duodenums were obtained 3, 7, 14, 28 days post-infection (PI) from five mice
      each group. Neodiplostomum specific IgA in serum by the enzyme-linked
      immunosorbent assay increased from 7 days PI and persisted till 28 days PI.
      Immunohistochemistry for IgA was done with sections of the duodenum. The IgA
      positive reaction was generally seen in the lamina propria and submucosa. Some of
      epithelial cells were positive at 7 and 14 days PI. The present finding showed
      that Neodiplostomun specific IgA antibody increased in serum and that there was
      local reaction of IgA in the mucosa and submucosa of the duodenum but not
      directly related with worm expulsion.

PMID- 7735787
TI  - Two cases of Gymnophalloides seoi infection accompanied by diabetes mellitus.
AB  - Gymnophalloides seoi, a new intestinal trematode of humans transmitted by oysters
      on a southwestern island of Korea, drew medical attentions because of its
      possible relationship with evoking pancreatitis or other pancreatic diseases. We
      experienced two interesting cases of G. seoi infection who were accompanied with
      diabetes mellitus. In routine stool examination, eggs of a gymnophallid were
      detected from two patients, and after treatment with praziquantel and purgation,
      772 and 10 adult flukes were recovered respectively. They were identified as G.
      seoi. The first patient was a 62-year old man who lived in Mokpo, nearby the
      known endemic area, and the second patient, a 54-year old woman who lived in
      Inchon. They used to eat raw oysters. It should be ruled out that G. seoi
      infection has some relationship with pancreatic diseases.

PMID- 7735788
TI  - Intestinal parasitic infections in the residents of an emigration camp in
      Tijuana, Mexico.
AB  - We examined stool specimens of the residents in the emigration camp in Tijuana,
      Mexico for helminth eggs or protozoan cysts with formalin-ethyl acetate
      concentration method in February and July 1992. Out of 92 examined samples,
      number of positive was 49 (53.3%). While number of cumulative positive was 66
      (71.7%). Cysts of Entamoeba coli (29.3%) Giardia lamblia (9.8%), Entamoeba
      histolytica (7.6%), and eggs of Taenia spp. (6.5) were most frequently observed.
      Filtered water supply and chemotherapy were required in this camp.

PMID- 7735789
TI  - Head louse infestation in vagrants and children admitted to public welfare
      facilities, Republic of Korea.
AB  - From December 1992 to February 1993, all vagrants and children admitted to public
      welfare facilities supported by the Government of Republic of Korea were examined
      for the presence of nit, nymph or adult of head louse. Of 36,055 persons
      examined, the number of positive was 7,393 (20.5%). Intensive control measures
      are needed to control this ectoparasitic infestation.

PMID- 7735790
TI  - [Effects of nutrient and salinity in egg and larval development of Aedes togoi].
AB  - The study made an observation on periodicity of oviposition, and the effects of
      nutrient and salinity in egg and larval development of Aedes togoi, and the
      results are summarized as follows: The 53.9% mosquitoes of one feeding laid eggs
      once, 26.9% laid twice and 19.2% laid three times. Autogenous rate of Aedes togoi
      reared in three different nutrient groups in larval sage was 6.9% in 0.8
      mg/larva, 22.5% in 1.6 mg/larva and 44.4% in 2.4 mg/larva. The oviposition rate
      according to different salinity of the oviposition sites (0%, 0.5%, 1.0%, 2.0%
      and 4.0%) was 25.2% in distilled water, 36.2% in 0.5% salinity, 23.5% in 1.0%
      salinity and 14.6% in 2.0% salinity. Developing period of the aquatic stage of
      male Aedes togoi in 25 degrees C were shorter (10.73 days) than females (11.85
      days). The most effective concentration of salinity for the developing period was
      1.0% which took 9.25 days in males and 10.44 days in females. In the
      developmental status of the follicles according to nutrition in the larval stage,
      the numbers of follicles of groups fed 0.8 mg, 1.6 mg and 2.4 mg per larva were
      180.7, 197.5 and 202 respectively. The result of ovary dissection on the 10th day
      after emergence, three different nutrition groups were in Christopher's stage IIa
      mostly; each 71.0%, 61.1% and 39.9% of the total follicles and autogenous females
      observed.

PMID- 7735791
TI  - Obituary: Harold Hopkins.

PMID- 7735792
TI  - Laparoscopic nephrectomy: Mansoura experience with 106 cases.
AB  - OBJECTIVE: To describe the technique and report our experience of laparoscopic
      nephrectomy. PATIENTS AND METHODS: Between August 1992 and December 1993, 106
      patients underwent laparoscopic nephrectomy at the Mansoura Urology and
      Nephrology Center. RESULTS: Of the 106 patients, laparoscopic nephrectomy was
      performed successfully in 97 cases. Conversion to an open procedure was necessary
      in the remaining nine patients. CONCLUSION: For a selected group of patients,
      laparoscopic nephrectomy is a feasible and safe technique. The length of hospital
      stay and convalescence is short and return to work is rapid.

PMID- 7735793
TI  - Laparoscopic nephrectomy: initial experience and cost implications.
AB  - OBJECTIVE: To assess the results and cost implications of laparoscopic
      nephrectomy. PATIENTS AND METHODS: Ten patients underwent attempted laparoscopic
      nephrectomy and nephro-ureterectomy. The cost of the laparoscopic procedures was
      estimated to allow comparison with that of open surgery. RESULTS: Two patients
      required conversion to an open procedure, one for a colonic tear, the other for
      irretrievable loss of pneumoperitoneum. The median operating time for successful
      cases was 3 h (range 2.5-4). The mean morphine equivalent of analgesia delivered
      per patient was 18 mg (range 10-28). There was no mortality. Post-operative
      complications consisted of one case of prolonged ileus and another of chest
      infection. The median hospital stay of successful cases was 5 days (range 4-17),
      and the mean time to return to normal activity was 4 weeks (range 3-6). The cost
      of the procedure using re-usable instruments was approximately 2000 pounds,
      comprising 100 pounds for equipment. 900 pounds theatre costs and 1000 pounds for
      hospital stay. Using disposable equipment adds up to 900 pounds to the cost. In
      comparison an open nephrectomy typically costs around 2300 pounds. CONCLUSION:
      Laparoscopic nephrectomy is associated with lower analgesia requirements, shorter
      hospital stay and quicker return to work than equivalent open procedures. The
      cost, particularly when performed with re-usable instruments, is not prohibitive
      being comparable with that of open nephrectomy. With further experience it should
      become part of the armamentarium of urological surgeons.

PMID- 7735794
TI  - Laparoscopy in 100 consecutive patients with 128 impalpable testes.
AB  - OBJECTIVE: To investigate the value of laparoscopy in boys with impalpable
      testes, to carry out a histological examination of testicular biopsies or
      orchidectomy specimens, and to present a clinical description of boys with
      impalpable testes. PATIENTS AND METHODS: One hundred consecutive patients
      underwent laparoscopy for 128 impalpable testes. They ranged in age from 2.7 to
      19.3 years (median 10.8). Histological examination was performed on 39 testicular
      biopsies, nine primarily orchidectomized testes and 13 tissue samples from the
      end of blind-ending vessels and vasa deferentia. Any additional diagnoses to that
      of impalpable testes were recorded. RESULTS: There were no complications
      associated with laparoscopy and the procedure clarified the situation in all
      patients. In 50% of patients either blind-ending cord structures above the
      internal inguinal ring or intra-abdominal testes were identified; in the
      remainder, cord structures could be seen passing through the ring, indicating an
      intracanalicular testis. The impalpable testis was absent in 77% of patients with
      a contralateral scrotal testis. A seminoma was found in one 18.6-year-old patient
      with bilateral cryptorchidism. No intratubular germ cell neoplasia (carcinoma in
      situ) was found. Germ cell hypoplasia or aplasia was demonstrated in 95% of
      patients with testicular parenchyma. Additional diagnoses were made in 49% of
      patients with bilaterally undescended testes (one or both of which were
      impalpable). CONCLUSION: We recommend laparoscopy as a safe procedure which leads
      to a diagnosis in patients with impalpable testes; the advent of laparoscopic
      procedures makes definitive treatment possible in about 50% of such patients.
      Open procedures will be indicated only to ascertain the quality and treatment of
      intracanalicular testes.

PMID- 7735795
TI  - Differences in the free Ca2+ in undiluted urine from stone formers and normal
      subjects using a new generation of ion-selective electrodes.
AB  - OBJECTIVES: To measure the ionized Ca2+ in urine from normal subjects and
      patients with urinary tract stones. PATIENTS AND METHODS: Urine samples were
      obtained from 37 normal subjects and 52 stone-formers. Ca2+ was measured using
      plastic dip-cast ion-selective electrodes; total Ca and other variables were
      measured by standard analytical techniques. RESULTS: The ionized Ca2+ and the
      total Ca were greater in stone-formers' urine although the difference was more
      significant with the Ca2+ data, especially at a standardized pH. Absolute values
      of the Ca2+ were dependent on the type of reference electrode used. The Ca2+ was
      a function of urine pH; lower values were recorded as pH increased. Measured
      values of the Ca2+ did not correlate well with calculated values using a standard
      computer program. CONCLUSIONS: Measurement of the Ca2+ in spot urine samples at a
      standard pH provides a more discriminative test than total Ca for the presence of
      urinary tract stones. The pH dependence of the Ca2+ may have important
      consequences in the formation of urinary tract stones. The poor correlation
      between measured and computed values of Ca2+ emphasizes the importance of
      accurate measurement of this variable.

PMID- 7735796
TI  - Glomerular filtration rate measurement: a neglected test in urological practice.
AB  - OBJECTIVES: To assess the accuracy and reproducibility of methods used to measure
      glomerular filtration rate (GFR) in clinical practice. PATIENTS AND METHODS:
      Simultaneous clearances of iohexol, 99mTc-diethylene-triamine-penta-acetic acid
      (DTPA), 24 h renal creatinine clearance and creatinine clearance estimated from a
      serum sample only, were obtained in 31 patients. Accuracy was calculated relative
      to iohexol clearance. The reproducibility of each method was determined by repeat
      measurements in the same individuals: three 99mTc-DTPA clearances in 21 patients;
      three 24 h creatinine clearance estimations in 12 patients; and three serum
      creatinine clearance estimations in 21 patients. RESULTS: The mean differences
      between 99mTc-DTPA clearance, 24 h renal creatinine clearance and estimated
      creatinine clearance compared with the reference method were 0.2 mL/min, 21.6
      mL/min and 0.6 mL/min, respectively. 99mTc-DTPA clearance had fairly tight 95%
      limits of agreement (12.2 mL/min) compared with 35.4 mL/min for 24 h creatinine
      clearance and 25.8 mL/min for estimated creatinine clearance. The reproducibility
      for each method was 5.4%, 24.3% and 6.1%, respectively. CONCLUSION: Single
      injection 99mTc-DTPA clearance provides an accurate and reproducible method of
      GFR measurement that is suitable for objective monitoring of renal function.
      Twenty-four hour creatinine clearance is neither sufficiently accurate nor
      reproducible for this purpose. Creatinine clearance estimation from a serum
      sample without urine collection may be preferable to the more traditional 24 h
      collection method.

PMID- 7735797
TI  - The National Prostatectomy Audit: the clinical management of patients during
      hospital admission.
AB  - OBJECTIVE: To determine everyday practice in the hospital management of men
      undergoing prostatectomy and the extent of its variation. PATIENTS AND METHODS: A
      total of 5361 patients, who represented 89% of all those undergoing prostatic
      procedures in four health regions (Mersey, Wessex, Northern and South West
      Thames) and one test site (within Trent) were recruited by 103 (97%) surgeons.
      Clinical information was collected on a pre-coded data collection form which was
      completed during the hospital stay by the principal operator. Patient
      identification occurred at the time of surgery. RESULTS: Important findings
      included: (i) both older men and those of higher social class were more likely to
      undergo prostatectomy with fewer symptoms; (ii) men who waited longer for surgery
      had worse symptoms by the time of their operation; (iii) there were unexplained
      differences in routine pre- and post-operative investigation and treatment. Half
      the men had their flow rate or residual urine measured as part of their pre
      operative assessment. About half the men received prophylactic antibiotics; (iv)
      when large groups were analysed, a consistent proportion of men throughout the
      study (12%) were undergoing the operation for a second time. The clinical course
      of men having a repeat operation differed in many ways from those having a first
      time procedure; (v) the larger proportion of men (62%) had surgery for strong
      indications as opposed to symptoms alone; (vi) although most operations were
      performed by consultants, emergency admissions, though symptomatically more
      severe and sicker, were more likely to be operated on by trainee surgeons; (vii)
      significant variation in mean pre-operative symptom severity and bother scores
      were seen between surgeons. CONCLUSION: The clinical management of prostatectomy
      has been defined in a large and representative UK sample. In some circumstances
      consistent variations have been identified. It is not yet clear whether these
      variations influence outcome. These data can be used by surgeons wishing to
      compare their own patient management with that described here.

PMID- 7735798
TI  - Experience with the second generation UroLume prostatic stent.
AB  - OBJECTIVE: To assess the efficacy of the new, second generation UroLume (American
      Medical Systems) prostatic stent. PATIENTS AND METHODS: Forty-seven men with
      symptomatic and objective evidence of bladder outflow obstruction who were fit
      for a transurethral resection accepted, as an alternative, the insertion of a new
      prostatic stent which shortens less than its predecessor. RESULTS: It was
      possible to insert the stent into 44 of the 47 men. All patients voided
      spontaneously following stent insertion. Thirty-three patients had their stent
      inserted either as a day case or with an overnight stay. Six patients were lost
      to follow-up and two died. Of the remaining 36 patients 22 have now been followed
      for 2 years, with a mean obstructive score of 1.6 (range 0-12), a mean irritative
      score of 2.5 (range 0-10) and a mean peak flow of 16.8 mL/s (range 3-31).
      Fourteen stents had to be removed; in the majority of cases this was because of
      stent migration or the development of epithelial hyperplasia within the lumen of
      the stent. CONCLUSION: Because of the development of epithelial hyperplasia and
      stent migration in approximately one-third of men in this study, a third
      generation stent has now been developed. Before permanently implanted stents can
      be recommended for widespread use, the efficacy of new stents should be assessed
      in specialist units with large numbers of patients and adequate facilities for
      follow-up.

PMID- 7735799
TI  - A comparative optical analysis of laser side-firing devices: a guide to
      treatment.
AB  - OBJECTIVE: To compare the optical characteristics of five different laser side
      firing fibres used to perform deep laser coagulation of the prostate. MATERIALS
      AND METHODS: The intensity profile, angle of exit and beam divergence from the
      launch fibre were measured underwater (to simulate endoscopic conditions) for
      each fibre using both the Helium Neon(633 nm) and Nd:YAG(1064 nm) lasers.
      RESULTS: The intensity profiles and spot sizes varied among fibres but broadly
      fell within two groups characterized by large and small footprints (low and high
      power density). There was a maximum 5.5 fold difference in average power
      densities between the fibres. CONCLUSIONS: Not all side-firing devices are the
      same. Variations in the power density profiles among the fibres suggest that the
      choice of fibre is of critical importance in determining the type of laser tissue
      interaction (i.e. coagulation or vaporization) that will follow the use of that
      fibre.

PMID- 7735800
TI  - Post-operative risk factors associated with artificial urinary sphincter
      infection-erosion.
AB  - OBJECTIVE: To determine the incidence of infection-erosion associated with the
      implantation of artificial urinary sphincters (AMS 800) in a high-risk group of
      patients (post-major pelvic surgery/radiotherapy), and to emphasize the commonly
      neglected risk factors associated with this complication. PATIENTS AND METHODS:
      One-hundred-and forty-five male patients aged 55-79 years (mean 71) who had had
      an AMS 800 artificial sphincter implanted between January 1987 and November 1993
      were reviewed. All patients had undergone meticulous surgical technique, intra
      operative shave and rigorous scrub, and were given peri-operative antibiotics.
      The mean follow-up was 34.3 months (range 1-83). RESULTS: Infection-erosion
      occurred in 13 patients (9%), of whom 10 are currently available for follow-up.
      One patient died of his underlying disease (bladder cancer) and two were lost to
      follow-up. All 13 patients had undergone radical pelvic surgery (radical
      retropubic prostatectomy, radical cystectomy and abdominoperineal resection);
      seven patients had also received radiation therapy. Cultures of the infected AMS
      800 devices revealed a pleomorphic group of organisms, specifically enteric, Gram
      positive and anaerobic organisms. The risk of infection-erosion was found to be
      increased in the presence of two main factors, improper urethral catheterization
      and urethral endoscopic manipulation with an activated AMS 800 artificial
      sphincter in place and exposure to radiation. At the time of revision, nine of
      the 13 patients were found to have positive urine cultures. CONCLUSION: Despite
      all the precautions taken, there remains a group of patients who are still at a
      higher risk of infection-erosion due to adverse circumstances that distort the
      anatomy of the perineal area, impair the host defence mechanisms, and ultimately
      enable the establishment of the infection-erosion complex. Radiotherapy is known
      to increase the likelihood of non-mechanical complications, specifically
      infection-erosion. Extreme care must be taken so that avoidable iatrogenic
      factors such as improper urethral catheterization and endoscopic manipulation
      with an activated AMS 800 device in situ are not the cause of 'failure'.

PMID- 7735801
TI  - Periurethral implantation of glutaraldehyde cross-linked collagen (Contigen) in
      women with type I or III stress incontinence: quantitative outcome measures.
AB  - OBJECTIVE: To evaluate the effectiveness of periurethral collagen (Contigen)
      implantation as a treatment for stress incontinence, using quantitative measures
      of urine loss and the patients' subjective response. PATIENTS AND METHODS: Twelve
      women, age range 46-87 years, had video urodynamic testing--confirming Type I or
      III stress urinary incontinence and were eligible for periurethral collagen
      implant. Eleven had had at least one anti-incontinence operation. One woman was
      withdrawn from the study because of a severe subcutaneous skin reaction 21 days
      after the skin-test and one patient declined follow-up. Ten patients had up to
      two implants each, introduced 3-5 months apart under local anaesthetic (5 mL
      collagen per implant). All patients underwent 10 h pad tests (with 2-hourly pad
      changes) at baseline and 8 weeks after collagen implant. The following
      quantitative measures of incontinence severity and voiding function were studied:
      urine loss during the 10 h test, number of wet pads, weight of urine in the
      wettest pad, maximum voided volume, residual volume on ultrasound, maximum flow
      rate and urinary flow curve pattern. Blind to the quantitative results, patients
      were asked to categorize their outcome as cured, improved and failed. RESULTS:
      There was a significant decrease in urine loss (P = 0.007), number of wet pads (P
      = 0.05) and weight of the wettest pad (g) (P = 0.03) from baseline to 8 weeks
      after the second collagen implant. There was no significant difference at any
      point in maximum voided volume, maximum urinary flow rate and residual volume
      after voiding measured on ultrasound. Objectively, two women appeared cured (< 5
      g urine loss on 10 h pad test); subjectively, both reported themselves as
      improved (not cured); one subject stated she was cured and on pad test had 11 g
      urine loss; two women stated there was no change yet urine loss decreased
      markedly by > 60% from 434 g to 123 g and 533 g to 199 g. The remaining six
      stated they were improved although, objectively, their urine loss after the
      collagen implant remained high (mean 132 g, range 87-185). CONCLUSION: These
      results show a significant reduction in urine loss at 8 weeks after the second
      collagen implant and an objective cure rate of 18%. There was little relationship
      between the objective measure of success and the self-report. Of interest is the
      fact that no obstructive changes occurred in the voided amount, the flow curve
      and the residual volume after voiding.

PMID- 7735802
TI  - Prognostic evaluation of morphonuclear parameters in superficial and invasive
      bladder cancer.
AB  - OBJECTIVE: To assess the prognostic value of morphonuclear parameters determined
      by means of computerized image analysis in untreated bladder tumours. PATIENTS
      AND METHODS: Fifty patients had untreated bladder cancer; in 28 patients the
      tumours were superficial (7pT1G1; 14pT1G2; 7pT1G3) and in 22 they were invasive
      (6T2G2, 9T2G3, 2T3G2, 5T3G3). Feulgen-stained imprints were processed for
      morphonuclear analysis on a SAMBA 200 computerized image analysis system (T1TN,
      France), which measures optical density (integrated optical density, IOD; surface
      area, SURF; mean optical density, MOD), texture (long run length, LRL; short run
      length, SRL; run length distribution, RLD; run length percentage, RLP; grey level
      distribution, GLD) and contrast (contrast, C; energy, E). RESULTS: Morphonuclear
      parameters IOD, SURF, LRL, SRL and C were found to correlate with the risk of
      recurrence and progression of superficial bladder tumours (results for ANOVA
      respectively IOD P < 0.001; SURF P = 0.02; LRL P = 0.05; RLD P = 0.04; SRL P =
      0.04; C P < 0.001). In invasive bladder cancer, parameters IOD and C only
      correlated with the risk of progression (ANOVA respectively IOD P < 0.001; C P <
      0.001). On the other hand, progression-free curve analysis using the Kaplan Meier
      method showed that morphonuclear parameters may be useful in predicting the
      outcome for superficial tumours (Log/Rank test: SURF P < 0.001; RLD < 0.001; SRL
      = 0.003; LRL < 0.001; C < 0.001; IOD < 0.001). In the case of invasive tumours,
      only two parameters provided prognostic information (Logrank test: C < 0.001; IOD
      < 0.001). CONCLUSION: Nuclear morphometry assessed by image analysis is
      potentially useful in assessing the prognosis of bladder tumours; it provides
      objective and quantitative parameters. Further studies will determine whether
      morphonuclear analysis can be used to monitor the treatment of bladder cancer,
      particularly superficial tumours.

PMID- 7735803
TI  - Treatment of penile curvature--a retrospective study of 175 patients operated
      with plication of the tunica albuginea or with the Nesbit procedure.
AB  - OBJECTIVE: To evaluate the outcome and complications after operative correction
      of sexually disabling penile angulation. PATIENTS AND METHODS: Between January 1
      1987 and December 31 1991, 175 patients underwent operative correction of penile
      angulation due to Peyronie's disease (57 patients) or congenital curvature (118
      patients). Thirty two patients were treated by plication of the tunica albuginea
      and 143 by the Nesbit procedure. Post-operatively 91% of the patients were seen
      in the out-patient clinic after 3-5 months. A questionnaire sent to all patients
      6-60 months after surgery was returned by 74% of the patients, and the present
      results are based on the most recent information obtained. RESULTS: In the
      plication group good or acceptable results were obtained in 12 of 32 patients
      (38%) after the first operation, and in a further nine patients (22%) after a
      second operation. In the Nesbit group 126 of 143 patients (88%) obtained good or
      acceptable results after the first operation and a further seven patients (5%)
      reported success after a second operation. The failures in the Nesbit group were
      due mainly to post-operative erectile dysfunction in patients with Peyronie's
      disease, in contrast to the plication group where failures were primarily due to
      recurrence of angulation. CONCLUSION: Operative correction of penile curvature is
      a reasonably safe procedure, but should not be performed solely for cosmetic
      reasons. In the present retrospective study the results were better after the
      Nesbit procedure compared with plication of the tunica albuginea. However, a
      review of the literature does not give support to one operative technique over
      the other. This can only be clarified by performing a prospective randomized
      trial.

PMID- 7735804
TI  - The role of tobacco in penile carcinoma.
AB  - OBJECTIVE: To study the role of tobacco in squamous cell carcinoma of the penis.
      SUBJECTS AND METHODS: The use of tobacco in the form of cigarettes, chewing
      tobacco and snuff was studied in a total of 503 patients and age-matched
      controls. RESULTS: By multivariate analysis, a significant association was found
      between smoking (P = 0.002) or chewing tobacco (P < 0.001) and the use of snuff
      (P = 0.004) in patients with penile carcinoma as compared with controls. A dose
      response relationship was observed for both smoking and chewing. CONCLUSIONS: The
      use of tobacco is a significant risk factor for penile carcinoma, and the use of
      more than one form of tobacco increases this risk.

PMID- 7735805
TI  - Development of peptide-containing nerves in the human fetal vas deferens and
      seminal vesicle.
AB  - OBJECTIVE: To use immunohistochemical methods to study the developing autonomic
      innervation of the human fetal vas deferens and seminal vesicle. MATERIAL AND
      METHODS: Thirteen pre-natal specimens ranging in gestational age from 13 to 30
      weeks were acquired following abortion or miscarriage. The overall innervation of
      each specimen was visualized using protein gene product 9.5 (PGP), a general
      nerve marker, while the onset and development of specific neuropeptide-containing
      sub-populations were investigated using antisera to neuropeptide Y (NPY),
      vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene related
      peptide (CGRP), bombesin (BOM), somatostatin (SOM), and met-enkephalin (ENK). In
      addition the occurrence and distribution of presumptive noradrenergic nerves was
      studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine
      hydroxylase (TH). RESULTS: At 13 weeks numerous PGP, D beta H, TH, NPY and ENK
      immunoreactive (-IR) nerve trunks were present in the adventitia of the vas
      deferens and seminal vesicle but at this stage nerve fibres were not present in
      the smooth muscle coat of either organ. By 17 weeks, fine PGP-, D beta H, and TH
      IR nerve fibres had penetrated the outer aspect of the muscle coat of the seminal
      vesicle but not the vas deferens. At 20 weeks a branching network of PGP-, D beta
      H- and TH-IR nerve fibres occurred throughout the full thickness of the muscle
      coat of the seminal vesicle while similar nerves were present only in the outer
      half of the muscle coat of the vas deferens. At 23 weeks the full thickness of
      the muscle coat of the vas deferens was richly innervated by a branching plexus
      of PGP-IR nerves. Many of these adventitial and intramuscular nerves were
      immunoreactive for D beta H or TH while some were immunoreactive for either NPY
      or ENK. Occasional adventitial nerves were immunoreactive for SP or CGRP, these
      being first observed at 20 weeks. VIP-IR nerves were extremely rare in the muscle
      coat of either organ, being first observed at 17 weeks in the seminal vesicle and
      at 20 weeks in the vas deferens where they mainly formed perivascular plexuses.
      PGP-IR nerves were first observed in the submucosa of the seminal vesicle at 20
      weeks and in the vas deferens at 21 weeks. Some of these nerves were perivascular
      in location while other formed a subepithelial plexus which increased in density
      with increasing gestational age. At 22 weeks of gestation some of the submucosal
      nerves were immunoreactive for SP or NPY, while at 30 weeks NPY-IR nerves formed
      the majority of subepithelial nerves. Occasional VIP-IR subepithelial nerves were
      first observed at 26 weeks but were extremely rare even at 30 weeks. Submucosal
      nerves immunoreactive for CGRP, D beta H, TH or ENK did not occur in any of the
      specimens examined. CONCLUSION: (i) From 13 weeks gestation autonomic nerves
      develop in the muscle coat of the fetal seminal vesicle and vas deferens, being
      denser in the seminal vesicle than the vas deferens up to 23 weeks gestation.
      (ii) The majority of the intramuscular nerves in either organ contain D beta H,
      TH, NPY and ENK and are presumably noradrenergic in type. (iii) A subepithelial
      nerve plexus develops around 20 weeks gestation and contains NPY but not VIP,
      unlike the adult organs. (iv) Scattered neuroendocrine cells immunoreactive for
      SOM are present in the mucosa of the seminal vesicle from 23 weeks of gestation.

PMID- 7735806
TI  - Treatment of neuropathic urinary and faecal incontinence with synchronous bladder
      reconstruction and the antegrade continence enema procedure.
AB  - OBJECTIVES: To report our experience with synchronous bladder reconstruction and
      the antegrade continence enema (ACE) procedure in the management of neuropathic
      urinary and faecal incontinence. PATIENTS AND METHODS: Eight patients (four boys,
      four girls) with a median age of 9 years 10 months (range 4.5-17) were treated.
      Five had spina bifida, two high ano-rectal malformations and one had been
      successfully treated for a spinal neuroblastoma. The appendix was used for the
      ACE procedure in five patients and a tubularized caecal or colonic flap in the
      other three. Seven patients had an augmentation cystoplasty and one a cystectomy
      with a continent diversion. A bladder neck reconstruction or an urethral
      lengthening procedure was performed in five patients and the bladder outlet was
      closed in two. Six patients required some form of revision. Four patients
      underwent a simultaneous Mitrofanoff procedure. RESULTS: The median length of
      follow-up was 11.5 months (range 3-29). Five patients were completely clean and
      the remaining three experienced minor faecal soiling only. They were all
      delighted with the result. Six patients were dry day and night, one was wet at
      night only while the final patient was wet day and night. CONCLUSIONS:
      Synchronous surgical procedures to make patients with neuropathic incontinence
      both clean and dry is effective, but most patients require revision surgery.
      Patient motivation and selection and the availability of a nurse specialist is
      crucial in obtaining satisfactory results.

PMID- 7735807
TI  - Endoscopic trigonoplasty for primary vesico-ureteric reflux.
AB  - OBJECTIVE: To investigate the surgical results of endoscopic trigonoplasty in
      patients with primary vesicoureteric reflux. PATIENTS AND METHODS: Records were
      reviewed for 12 patients who underwent endoscopic trigonoplasty between February
      1992 and February 1994. Of the 12 patients, 11 were female; one was a child and
      nine had unilateral disease. From 15 renoureteric units, grade I vesico-ureteric
      reflux was demonstrated in five, grade II in six and grade III in four. The
      ureteric orifices were approximated close to the midline via the urethral route
      and two trocars on the abdomen achieved pneumobladder. RESULTS: The mean surgical
      time was 178 +/- 52 min; this lessened as the learning curve developed. Intra
      operative complications in three patients were all caused by trocar placement.
      Eleven patients required analgesics for one post-operative day only. No post
      operative dilatation of the upper urinary tract was demonstrated. Vesico-ureteric
      reflux was eradicated in all patients. CONCLUSIONS: Endoscopic trigonoplasty is a
      minimally invasive procedure with a high cure rate. By not destroying the normal
      vesico-ureteric junction, post-operative obstruction cannot occur. We believe
      that endoscopic trigonoplasty is a feasible procedure for patients with vesico
      ureteric reflux.

PMID- 7735808
TI  - Experience with ureteroscopy in children.
AB  - OBJECTIVE: To present our experience of ureteroscopic procedures in children
      using miniaturized instrumentation. PATIENTS AND METHODS: Fourteen children aged
      between 13 months and 14 years underwent 20 ureteroscopic procedures. Semi-rigid
      7.2 F and flexible 9.5 F ureteroscopes were used in a retrograde and an antegrade
      fashion. Eighteen ureteroscopies were performed retrogradely and two antegradely.
      Of the 20 ureteroscopic procedures, 18 were for stone disease, one for haematuria
      of unknown origin and one for removal of a migrated stent. The average size of
      the stone was 12.9 x 6.6 mm. RESULTS: Access using miniaturized ureteroscopes was
      successful in all patients. Dilatation was required only in 1 of 20 procedures.
      The management of stone disease in 10 of 13 children was straightforward and a
      single ureteroscopy was required to clear the ureters. In three of 13 children
      with stone disease the problems were more complex and nine ureteroscopies were
      undertaken to render the ureters stone free. Complications were stricture at the
      site of stone impaction (one patient), retention of urine due to a stone fragment
      in the urethra (one patient), haematuria (one patient) and migrated stent
      requiring ureteroscopy (one patient). CONCLUSION: In the hands of an experienced
      surgeon ureteroscopy can be used with equal success in children as in adults to
      treat calculus disease.

PMID- 7735809
TI  - Pseudoureterocele: potential for misdiagnosis of an ectopic ureter as a
      ureterocele.
AB  - OBJECTIVE: To present several case reports of children with 'pseudoureteroceles'.
      Familiarization with this entity should help to avoid an error in diagnosis and
      possible improper therapy. PATIENTS AND METHODS: Three girls with ectopic ureters
      entering mesonephric duct cysts are presented for review. RESULTS: Misdiagnosis
      of the pseudoureterocele as an ectopic ureter was made in two children. The
      'pseudoureterocele' may lie dormant for many years and often presents with acute
      urinary incontinence and/or onset of urinary tract infections. Resection of the
      dysplastic kidney and ipsilateral ureter, marsupialization of the cyst into the
      vagina, and closure of the vesical fistula is the preferred treatment.
      CONCLUSION: An ectopic ureter draining into a Gartner's duct cyst can be confused
      with an ectopic ureterocele. Correct diagnosis is vital to ensure proper
      treatment.

PMID- 7735810
TI  - The Miller Endocut Needle: single access direct vision core biopsy.

PMID- 7735811
TI  - Extracorporeal shock wave lithotripsy for lower ureteric stones through perineal
      region.

PMID- 7735812
TI  - Large cell calcifying Sertoli cell tumour.

PMID- 7735813
TI  - Conservative management of penile gangrene.

PMID- 7735814
TI  - Epididymal and renal sarcoidosis.

PMID- 7735815
TI  - Ureteric flap technique for recurrent vesicovaginal fistula caused by Teflon
      injection.

PMID- 7735816
TI  - Extracorporeal shock wave lithotripsy of renal calculi in a patient with
      haemophilia A complicated by a high titre factor VIII inhibitor.

PMID- 7735817
TI  - Iatrogenic duodeno-cutaneous fistula at percutaneous nephrolithotomy managed
      conservatively.

PMID- 7735818
TI  - Hydatid cyst in an undescended testis.

PMID- 7735819
TI  - Ureteroscopy through vesicostomy.

PMID- 7735820
TI  - Bladder cancer during pregnancy.

PMID- 7735821
TI  - Neuroanatomy of the human striated urethral sphincter.

PMID- 7735822
TI  - Duplex ureters--a pitfall during ileal ileal conduit urinary diversion.

PMID- 7735823
TI  - Reply to editorial "Dissemination and commercialization of hematopoietic
      progenitor cell transplantation," Volume 3, Number 2, 1994.

PMID- 7735824
TI  - Does cord blood contain enough progenitor cells for transplantation?
AB  - We analyzed 125 blood samples obtained from umbilical cord immediately after
      delivery of full-term neonates. Between 0.1 and 10.4% (mean 1.13%, SD 1.34) of
      the density-separated glycophorin A (GPA)-negative mononuclear cells (MNC)
      expressed CD34 as analyzed by flow cytometry. These hematopoietic progenitor
      cells did not coexpress CD19, and the majority were negative for CD45RA. The
      number of MNC determined per ml cord blood ranged from 1 x 10(5) to 200 x 10(5)
      (mean 20.2 x 10(5), SD 24.7). Regression analysis revealed that a mean of 56% (n
      = 26, R = 0.8) and 120% (n = 35, R = 0.94) of the analyzed CD34+ MNC gave rise to
      day 14 colonies in the clonogenic assay when cultured without or with stem cell
      factor (SCF). The number and the exact phenotype of progenitor cells required for
      successful transplantation are not known. If the transplantation of 5 x 10(5)
      CD34% cells/kg body weight is required for engraftment and one-third of the
      progenitor cells are lost to cell processing, and if 180 ml blood can be
      collected from a single umbilical cord (and placenta), our data suggest that 90%
      of the collections do not contain enough precursors to transplant a 25 kg
      recipient. To meet these conditions, an average of 1439 ml cord blood would be
      necessary for transplantation.

PMID- 7735825
TI  - Peripheral blood progenitor cells versus bone marrow.
AB  - Transplantation of mobilized peripheral blood progenitor cells has generally
      produced shortening of the period of posttransplant aplasia that is
      characteristic of bone marrow grafts. However, there has been no large
      prospective randomized study to compare these two sources of hematopoietic cells
      or to determine their relative merits. This issue is explored in this review.

PMID- 7735826
TI  - Antisense strategies for the control of aberrant gene expression.
AB  - Antisense nucleic acids have been shown to be potent and specific inhibitors of
      gene expression and viral replication in cells from various species, including
      mammals. Their potential applicability in vivo has been demonstrated by the use
      of antisense oligonucleotides and antisense RNA transcribed from recombinant
      antisense genes, respectively. It is conceivable that both classes of antisense
      nucleic acids can be used to correct pathogenic cellular or viral gene
      expression, thereby extending the range of therapeutic options from new
      techniques developed in the field of molecular biology. Possible improvements in
      the inhibitory potential of antisense nucleic acids and selected points to
      consider concerning their design, their function, and their application are
      discussed.

PMID- 7735827
TI  - Detection and characterization of residual disease in breast cancer.
AB  - Although micrometastatic tumor cell spread largely determines the prognosis of
      patients with operable breast cancer, it is usually missed by conventional tumor
      staging. Several groups (including ours) have therefore developed
      immunocytochemical and molecular assays that allow the specific detection and
      characterization of individual carcinoma cells disseminated to bone marrow,
      blood, and lymph nodes. These assays may improve the prognostic precision of the
      current classification systems and may provide a tool for the early assessment of
      the therapeutic effects of anticancer drugs on micrometastatic cells in
      individual patients. Another aspect of such methods is that they enable detection
      of tumor cell contamination in stem cell grafts and validation of the efficiency
      of purging techniques. The most extensive experience exists with
      immunocytochemical methods, some of which have the potential to serve as a
      benchmark for less validated molecular methods. Still, the specificity and
      sensitivity of immunocytochemical detection of single cancer cells are affected
      by several variables, which include the intricacies of antigen expression, the
      lack of distinct morphological characteristics, the size of the analyzed sample,
      and the staining techniques for visualization of antibody binding. This article
      provides a critical review of the opportunities and pitfalls related to new
      methods for the detection and monitoring of minimal residual disease in breast
      cancer.

PMID- 7735829
TI  - Structure of the NF-kappa B transcription factor: a holistic interaction with
      DNA.
AB  - An unexpected mode of binding to DNA is revealed in two crystal structures of a
      transcription factor that is essential for many signalling pathways in eukaryotic
      cells.

PMID- 7735828
TI  - Recombining the structures of HIV integrase, RuvC and RNase H.
AB  - The recently reported crystal structures of two recombination enzymes, the
      catalytic domain of HIV integrase and Escherichia coli RuvC, an endonuclease, are
      surprisingly similar to that of ribonuclease H suggesting the possibility that
      they have a common enzymatic mechanism.

PMID- 7735830
TI  - Apoptosis research enters the ICE age.
AB  - Recent elucidation of the structure of interleukin-1 beta-converting enzyme
      (ICE), a protease with sequence homology to a nematode protein associated with
      programmed cell death, opens a new chapter in the study of how proteases may
      control cellular suicide.

PMID- 7735831
TI  - Entropy, likelihood and phase determination.

PMID- 7735832
TI  - Single-stranded DNA-protein interactions in canine parvovirus.
AB  - BACKGROUND: Parvoviruses are small icosahedral single-stranded (ss) DNA viruses
      which replicate in rapidly proliferating cells, causing a variety of serious and
      often lethal diseases in mammals, including humans. The structure of canine
      parvovirus (CPV) showed an 11-nucleotide oligomeric fragment of its genome bound
      to 60 equivalent binding sites on the inside surface of the capsid. This provides
      an opportunity to study the conformation of ssDNA, its interactions with protein,
      and its role in viral assembly. RESULTS: The icosahedrally ordered part of CPV
      ssDNA has an unusual loop conformation with the bases pointing outwards and the
      phosphates surrounding metal ions on the inside. The protein interacts with the
      bases, making 15 putative hydrogen bonds. The DNA electron density indicates
      preferences for particular base types in parts of the binding site. Statistical
      analysis of the genome yields approximately 30 regions with sequences similar to
      that observed in the structure, demonstrating a low level of sequence specificity
      for binding to capsid protein. CONCLUSIONS: ssDNA can adopt unusual conformations
      upon association with protein by using phosphoribose backbone rotamers that are
      found in tRNA, but not in DNA duplexes. The CPV DNA-protein interactions differ
      from the non-specific backbone interactions seen in some plant and insect
      viruses. The sequence specificity, albeit low level, of the protein for CPV DNA
      may contribute both to distinguishing the viral DNA from other nucleic acids and
      to the DNA packaging process during viral assembly.

PMID- 7735833
TI  - The crystal structure of the lysyl-tRNA synthetase (LysU) from Escherichia coli.
AB  - BACKGROUND: Lysyl-tRNA synthetase catalyzes the attachment of the amino acid
      lysine to the cognate tRNA. The enzyme is a member of the class II amino-acyl
      tRNA synthetases; the crystal structures of the seryl- and aspartyl-tRNA
      synthetases from this class are already known. Lysyl-tRNA synthetase shows
      extensive sequence homology with aspartyl-tRNA synthetase. In Escherichia coli
      there are two isoforms of the enzyme, LysS and LysU. Unlike LysS, which is
      synthesized under normal growth conditions, LysU is the product of a normally
      silent gene which is overexpressed under extreme physiological conditions (such
      as heat-shock), and can synthesize a number of adenyl dinucleotides (in
      particular AppppA). These dinucleotides have been proposed to act as modulators
      of the heat-shock response and stress response. RESULTS: The crystal structure of
      E. coli LysU has been determined to 2.8 A resolution, with lysine bound to the
      active site. The protein is a homodimer, with a rather extended dimer interface
      spanning the entire length of the molecule. Each monomer consists of two domains:
      a smaller N-terminal domain which binds the tRNA anticodon, and a larger C
      terminal domain with the topology characteristic of the catalytic domain found in
      class II synthetases. CONCLUSIONS: A comparison of the LysU crystal structure
      with the structures of seryl- and aspartyl-tRNA synthetases enables a conserved
      core to be identified. The structural homology with the aspartyl-tRNA synthetase
      extends to include the anticodon-binding domain. When the active sites of lysyl-,
      aspartyl- and seryl-tRNA synthetases are compared, a number of catalytically
      important residues are conserved and a similar extended network of hydrogen bonds
      can be observed in the amino acid binding pocket in all three structures,
      although the details may differ. The lysine substrate is involved in an extended
      network of hydrogen bonds and polar interactions, with the side chain amino group
      forming a salt bridge with Glu428. The binding of ATP to LysU can be modelled on
      the basis of the aspartyl-tRNA synthetase-ATP complex, but the tRNA acceptor stem
      interaction for LysU cannot be easily modelled by similar extrapolation.

PMID- 7735834
TI  - The refined structure of the quinoprotein methanol dehydrogenase from
      Methylobacterium extorquens at 1.94 A.
AB  - BACKGROUND: Methanol dehydrogenase (MDH) is a bacterial periplasmic quinoprotein;
      it has pyrrolo-quinoline quinone (PQQ) as its prosthetic group, requires Ca2+ for
      activity and uses cytochrome cL as its electron acceptor. Low-resolution
      structures of MDH have already been determined. RESULTS: The structure of the
      alpha 2 beta 2 tetramer of MDH from Methylobacterium extorquens has now been
      determined at 1.94 A with an R-factor of 19.85%. CONCLUSIONS: The alpha-subunit
      of MDH has an eight-fold radial symmetry, with its eight beta-sheets stabilized
      by a novel tryptophan docking motif. The PQQ in the active site is held in place
      by a coplanar tryptophan and by a novel disulphide ring formed between adjacent
      cysteines which are bonded by an unusual non-planar trans peptide bond. One of
      the carbonyl oxygens of PQQ is bonded to the Ca2+, probably facilitating attack
      on the substrate, and the other carbonyl oxygen is out of the plane of the ring,
      confirming the presence of the predicted free-radical semiquinone form of the
      prosthetic group.

PMID- 7735835
TI  - High-resolution crystal structure of the non-specific lipid-transfer protein from
      maize seedlings.
AB  - BACKGROUND: The movement of lipids between membranes is aided by lipid-transfer
      proteins (LTPs). Some LTPs exhibit broad specificity, transferring many classes
      of lipids, and are termed non-specific LTPs (ns-LTPs). Despite their apparently
      similar mode of action, no sequence homology exists between mammalian and plant
      ns-LTPs and no three-dimensional structure has been reported for any plant ns
      LTP. RESULTS: We have determined the crystal structure of ns-LTP from maize
      seedlings by multiple isomorphous replacement and refined the structure to 1.9 A
      resolution. The protein comprises a single compact domain with four alpha-helices
      and a long C-terminal region. The eight conserved cysteines form four disulfide
      bridges (assigned as Cys4-Cys52, Cys14-Cys29, Cys30-Cys75, and Cys50-Cys89)
      resolving the ambiguity that remained from the chemical determination of pairings
      in the homologous protein from castor bean. Two of the bonds, Cys4-Cys52 and
      Cys50-Cys89, differ from what would have been predicted from sequence alignment
      with soybean hydrophobic protein. The complex between maize ns-LTP and
      hexadecanoate (palmitate) has also been crystallized and its structure refined to
      1.8 A resolution. CONCLUSIONS: The fold of maize ns-LTP places it in a new
      category of all-alpha-type structure, first described for soybean hydrophobic
      protein. In the absence of a bound ligand, the protein has a tunnel-like
      hydrophobic cavity, which is large enough to accommodate a long fatty acyl chain.
      In the structure of the complex with palmitate, most of the acyl chain is buried
      inside this hydrophobic cavity.

PMID- 7735836
TI  - The oestrogen receptor recognizes an imperfectly palindromic response element
      through an alternative side-chain conformation.
AB  - BACKGROUND: Structural studies of protein-DNA complexes have tended to give the
      impression that DNA recognition requires a unique molecular interface. However,
      many proteins recognize DNA targets that differ from what is thought to be their
      ideal target sequence. The steroid hormone receptors illustrate this problem in
      recognition rather well, since consensus DNA targets are rare. RESULTS: Here we
      describe the structure, at 2.6 A resolution, of a complex between a dimer of the
      DNA-binding domain from the human oestrogen receptor (ERDBD) and a non-consensus
      DNA target site in which there is a single base substitution in one half of the
      palindromic binding site. This substitution results in a 10-fold increase in the
      dissociation constant of the ERDBD-DNA complex. Comparison of this structure with
      a structure containing a consensus DNA-binding site determined previously, shows
      that recognition of the non-consensus sequence is achieved by the rearrangement
      of a lysine side chain so as to make an alternative base contact. CONCLUSIONS:
      This study suggests that proteins adapt to recognize different DNA sequences by
      rearranging side chains at the protein-DNA interface so as to form alternative
      patterns of intermolecular contacts.

PMID- 7735837
TI  - Structural basis for the specific interaction of lysine-containing proline-rich
      peptides with the N-terminal SH3 domain of c-Crk.
AB  - BACKGROUND: Proline-rich segments in the guanine nucleotide exchange factor C3G
      bind much more strongly to the N-terminal Src homology 3 domain (SH3-N) of the
      proto-oncogene product c-Crk than to other SH3 domains. The presence of a lysine
      instead of an arginine in the peptides derived from C3G appears to be crucial for
      this specificity towards c-Crk. RESULTS: In order to understand the chemical
      basis of this specificity we have determined the crystal structure of Crk SH3-N
      in complex with a high affinity peptide from C3G (PPPALPPKKR, Kd approximately 2
      microM) at 1.5 A resolution. The peptide adopts a polyproline type II helix that
      binds, as dictated by electrostatic complementarity, in reversed orientation
      relative to the orientation seen in the earliest structures of SH3-peptide
      complexes. A lysine in the C3G peptide is tightly coordinated by three acidic
      residues in the SH3 domain. In contrast, the co-crystal structure of c-Crk SH3-N
      and a peptide containing an arginine at the equivalent position (determined at
      1.9 A resolution) reveals non-optimal geometry for the arginine and increased
      disorder. CONCLUSIONS: The c-Crk SH3 domain engages in an unusual lysine-specific
      interaction that is rarely seen in protein structures, and which appears to be a
      key determinant of its unique ability to bind the C3G peptides with high
      affinity.

PMID- 7735838
TI  - Limiting response alternatives in time-intensity scaling: an examination of the
      halo-dumping effect.
AB  - Time-related measurements pose some challenges to psychophysics and to applied
      sensory testing methods including control of psychological biases which have been
      found in single-point scaling. This research examined enhancement of ratings when
      response alternatives were limited in time-intensity scaling tasks using repeated
      category ratings. Panelists rated a pseudo-beverage containing sweetener and
      flavor and one with sweetener only over a 90-s period. The aromatic flavor caused
      an increase in sweetness intensity and especially so when the panelists were
      limited to sweetness responses only. The odor-induced enhancement of sweetness
      was smaller when panelists were given both flavor and sweetness response options
      than when the panelists were given only a sweetness scale. Prior use of both
      scales in a previous experimental session did not lessen the halo-dumping
      enhancement effect. In one study, sweetness ratings of sucrose alone were
      depressed when the additional scale for flavoring was provided, perhaps due to
      inappropriate partitioning of responses.

PMID- 7735839
TI  - Hydrolysis of sucrose octa-acetate: qualitative differences in taster and
      demistaster avoidance phenotypes.
AB  - Calcium hydroxide and sodium hydroxide were used to hydrolyse sucrose octa
      acetate (SOA) as a means of evaluating the taster (Soaa) and demitaster (Soac)
      allelic phenotypes of the genetic locus Soa. The SWR/J (taster) inbred strain and
      the B6.SW Soaa (taster) congenic strain were demonstrated to cease avoiding upon
      nearly complete hydrolysis of 10(-5) M SOA with calcium hydroxide or sodium
      hydroxide and of 10(-4) M SOA with calcium hydroxide. The BALB/cByJ, C3HeB/FeJ
      and DBA/2J (demitaster) inbred strains were demonstrated to cease avoiding after
      only a partial hydrolysis of 10(-3) M SOA using calcium hydroxide. It is
      suggested that specificity for the number or placement of the acetates of SOA
      underlies the difference between the taster and demitaster phenotypes.

PMID- 7735840
TI  - Olfactory responses of chum salmon to amino acids are independent of large
      differences in salt concentrations between fresh and sea water.
AB  - In chum salmon captured at the coastal sea and the natal river, the magnitudes of
      the olfactory nerve responses to the amino acids after perfusion of the olfactory
      epithelium with artificial pond water (APW) were similar to those after perfusion
      with artificial sea water (ASW), although the concentrations of Na+, Cl- and Ca2+
      in ASW were 986, 430 and 27 times higher than those in APW, respectively. The
      findings suggest that the permeability of these ions across the apical membranes
      of olfactory cells do not essentially contribute to the transduction mechanism in
      the salmon.

PMID- 7735841
TI  - Different responsiveness of the chorda tympani and glossopharyngeal nerves to L
      lysine in mice.
AB  - Differential taste responsiveness and functional role of the two taste nerves,
      the chorda tympani (CT) and the glossopharyngeal (GL), were studied in mice by
      examining neural and behavioral responses to an essential amino acid, L-lysine
      (Lys). Relative responses to Lys were larger in the GL than in the CT nerve. The
      neural threshold for the Lys response was about 2.5 log units lower in the GL
      (about 1.0 microM) than in the CT nerve (about 300 microM). An analysis of
      concentration-response relationships suggests a possibility that there are two
      different receptors (high and low affinity types) for Lys showing different
      dissociation constants. The posterior tongue region possesses both types, while
      the anterior region possesses only the low affinity type. Behavioral aversion
      threshold for Lys in intact mice, measured by use of a single bottle test, was
      about 1.0 microM. This threshold was the same as its neural threshold in the GL
      nerve. Animals whose bilateral GL nerves were sectioned showed a higher aversion
      threshold (about 300 microM) which was the same as the neural threshold in the CT
      nerve. An aversion conditioned to Lys significantly generalized to L-arginine in
      the intact and CT-denervated mice, and L-arginine and L-histidine in the GL
      denervated mice, but the generalization pattern across various taste stimuli
      including the four basic taste stimuli (NaCl, HCl, quinine HCl and sucrose) did
      not prominently differ among the intact, the GL-denervated and CT-denervated
      mice. These results suggest that taste sensitivity to Lys is higher in the GL
      than in the CT nerve, but taste quality information for Lys conveyed by two taste
      nerves is not largely different.

PMID- 7735843
TI  - Competitive inhibition of the nickel-induced response to choline by calcium ions
      in single water fibers of the frog glossopharyngeal nerve.
AB  - NiCl2 induces a response to choline Cl and enhances the response to CaCl2 in
      water-sensitive fibers (water fibers) of the frog glossopharyngeal nerve. The
      Ni(2+)-induced choline+ response was inhibited by Ca2+ ions and, conversely, the
      enhanced Ca2+ response by Ni2+ ions was inhibited by choline+ ions. Hence, there
      exists a mutual antagonism between Ca2+ and choline+ ions. In the present study,
      the inhibition of the Ni(2+)-induced choline+ response by Ca2+ ions was
      investigated quantitatively. The assumption was made that receptors for choline
      (XCh) exist and that binding of a choline+ ion to XCh brings about a neural
      response. It was further assumed that the magnitude of the neural response is
      proportional to the amount of choline-XCh complex minus some constant (the
      threshold concentration of the choline-XCh complex). The results from analysis of
      double-reciprocal plot were consistent with the hypothesis that Ca2+ ions compete
      with choline+ ions for XCh. The dissociation constants for the choline-XCh
      complex and the CaXCh complex were obtained to be 0.6 M and 7.4 x 10(-5) M,
      respectively. This result indicates that the affinities of XCh for choline+ and
      Ca2+ ions are very different. Furthermore, Mg2+ ions did not affect the Ni(2+)
      induced choline+ response, an indication that the affinity of XCh is not charge
      specific, but is chemically specific. The identification of a competitive
      inhibitor of the choline+ response provides evidence for existence of a choline
      specific receptor at the surface of taste cells that are innervated by the water
      fibers of the frog glossopharyngeal nerve. Differences between the features of
      the response to choline Cl in the chorda tympani nerve of the rat and those in
      the frog glossopharyngeal nerve are discussed.

PMID- 7735842
TI  - The responses to choline ions induced by transition metal ions in single water
      fibers of the frog glossopharyngeal nerve.
AB  - In single water-sensitive fibers (water fibers) of the frog glossopharyngeal
      nerve, application of a solution of 500 mM choline C1 to the tongue elicited
      responses of varying magnitude. Some water fibers (plain choline-insensitive
      water fibers) barely responded to the solution, while some water fibers (plain
      choline-sensitive water fibers) exhibited a considerable response to this
      solution. NiCl2, which is barely effective in producing neural response at
      concentrations below 5 mM, induced the response of plain choline-insensitive
      water fibers to choline+ ions. It was confirmed, in a collision test, that the
      Ni(2+)-induced responses to choline+ ions were derived from water fibers.
      However, NiCl2 did not affect the magnitude of the response generated by choline+
      ions in plain choline-sensitive water fibers. The concentration-response curve
      for choline C1 in the presence of 1 mM NiCl2 for plain choline-insensitive water
      fibers was similar to the curves obtained in the absence of NiCl2 for plain
      choline-sensitive water fibers. Other organic salts, such as
      tris(hydroxymethyl)aminomethane-HCl, triethanolamine-HCl and tetraethylammonium
      C1, elicited no response or only a very small response from water fibers, and
      NiCl2 did not affect these responses. It is suggested that there exists a choline
      receptor for the response to choline+ ions in the apical membrane of frog taste
      cells and that Ni2+ ions expose the sites of such choline receptors, which are
      deeply embedded in the receptor membrane, to the outside medium. The effect of
      Ni2+ ions results in an increase in the number of the choline receptor sites
      available for binding of choline+ ions. The rank order of effectiveness of
      transition metal ions in eliciting the appearance or enhancement of the response
      to choline C1 was Ni2+ > Co2+ > Mn2+. Mg2+ ions had no effect on the response to
      choline+ ions. A similar rank order was previously obtained in enhancement of the
      responses to Ca2+, Mg2+ and Na+ ions (Kitada, 1994a). It seems likely that the
      mechanism for enhancement or elicitation of the response to choline+ ions by the
      transition metal ions has features in common with that for enhancement of the
      responses to Ca2+, Mg2+ and Na+ ions.

PMID- 7735844
TI  - The effects of prior experience with capsaicin on ratings of its burn.
AB  - The experiments reported here found that judgments of 'burn' intensity are
      affected by long-term memory (LTM). The implication of these findings for range
      frequency theory and the role of LTM in intensity judgments are discussed.

PMID- 7735845
TI  - Effects of chorda-lingual nerve injury and repair on human taste.
AB  - Citric acid detection threshold and magnitude response were measured on the
      anterior tongue in 10 patients with unilateral chorda-lingual nerve transections
      before and after repair. Fungiform taste buds were analysed by videomicroscopy.
      Preliminary data suggests that humans can regenerate fungiform taste buds and
      recover some taste sensitivity after repair.

PMID- 7735846
TI  - Retroviral lineage studies of the rat olfactory epithelium.
AB  - Replication-incompetent retroviral vectors that encode the heritable marker
      enzyme, beta-galactosidase, were used to study the lineage relationships of cells
      in the olfactory epithelium of unmanipulated animals and in the olfactory
      epithelium as it reconstitutes after lesion. Virally-marked cells are categorized
      as to type based on their position in the epithelium and on expression of NCAM
      (limited to neurons) and the carbohydrate moiety recognized by Griffonia lectin
      (limited to the dark/horizontal basal cells and the microvillar class of
      supporting cells). Direct injections of the vectors into the olfactory epithelium
      of otherwise intact animals produce clusters of beta-galactosidase-labeled cells
      when assessed 6-10 days after infection; these clusters are composed of neurons
      and NCAM-negative/lectin-negative light/globose basal cells exclusively. In
      contrast, clusters of virally-marked cells after MeBr-induced lesion of the
      epithelium frequently contain both neurons and supporting cells, as well as both
      types of basal cells. Other clusters contain supporting cells and/or Bowman's
      gland/duct cells. It is likely that the clusters of marked cells are derived from
      a single founder cell, i.e. the cells are clonal and lineally related, since the
      clusters are widely dispersed. Furthermore, infusion of mixtures of viruses that
      can be distinguished on the basis of the type and subcellular localization of the
      marker enzyme that is expressed produce clusters that are homogenous with respect
      to enzyme type, providing strong evidence in favor of the notion that the
      clusters are clonal in nature. Thus, the founders of the clones that contain
      neurons, supporting cells and basal cells are pluripotent in their capacity for
      differentiation. It is unlikely that the pluripotent cells are found in Bowman's
      gland/duct, since we have yet to observe a clone that contains neurons and cells
      in Bowman's gland/duct. Hence, the pluripotent stem cells are to be found in the
      basal cell compartment of the epithelium. However, the exact nature of these stem
      cells remains unknown and a subject for future investigation.

PMID- 7735847
TI  - Lineage analysis of the olfactory epithelium using a replication-incompetent
      retrovirus.
AB  - We have analysed the lineage of olfactory receptor neurons using a replication
      incompetent retrovirus injected beneath the olfactory epithelium of young rats.
      There are two major types of clusters of infected cells seen at 5--40 days after
      infection: (i) horizontal basal cells (HBCs); (ii) variable numbers of globose
      basal cells (GBCs), and immature and mature sensory neurons. Olfactory nerve
      lesion increased the frequency of the globose/sensory neuron clusters, as well as
      the number of cells/cluster, but did not change the number of HBC clusters or
      cells/cluster. No clusters contained sustentacular cells. These data indicate
      that, at least in young rats: (i) HBCs are not precursors of olfactory neurons;
      (ii) there is a lineage path from GBCs to mature neurons; and (iii) sustentacular
      cells arise from a separate lineage.

PMID- 7735848
TI  - Rate and pattern of migration of lineally-related olfactory bulb interneurons
      generated postnatally in the subventricular zone of the rat.
AB  - A spatially discrete region of the anterior part of the postnatal telencephalic
      subventricular zone, referred to as the SVZa generates vast numbers of lineally
      related neurons destined for the olfactory bulb (Luskin, 1993). The cells
      originating in the SVZa migrate to the olfactory bulb along a highly restricted
      pathway which is in a direction orthogonal to the orientation of radial glial
      fibers. In this study we analysed the number, distribution, orientation and rate
      of migration of SVZa-derived cells as they approach the olfactory bulb. In order
      to track the SVZa-derived cells, a retroviral lineage tracer, encoding the
      reporter gene E. coli beta-galactosidase (lacZ) was injected precisely into the
      rat SVZa at postnatal day 1 (P1). The lacZ-positive cells were visualized 1, 2
      and 3 days later by X-Gal histochemistry in cryostat sections. As the number of
      SVZa-derived cells in the pathway increased with survival time, their
      distribution changed systematically. The distribution pattern of lacZ-positive
      cells by 2 and 3 days postinjection suggested that some of the progeny of
      infected progenitor cells were undergoing neurogenesis as they proceeded to the
      olfactory bulb; a large percentage of the lacZ-positive cells were substantially
      displaced from the SVZa injection site. To investigate whether lacZ-positive
      cells migrate in a directed fashion, their orientation preference was scored. For
      the majority of lacZ-positive cells (> 94%), their leading process was directed
      toward the olfactory bulb, possibly reflecting a response to migratory cues
      present along the pathway. The estimated average rate of cell migration to the
      olfactory bulb was 23 mu m/h, which is approximately twice the speed of radially
      directed neuronal migration from the telencephalic ventricular zone to the
      cortical plate (O'Rourke et al., 1992). Collectively, these results suggest that
      SVZa-derived interneurons en route to the olfactory bulb may employ a novel mode
      of tangential migration.

PMID- 7735849
TI  - Analysis of the embryonic lineage of vertebrate taste buds.
AB  - In all vertebrates, taste buds are the last sensory receptors to appear late in
      embryonic development. They are thought to arise locally from the oropharyngeal
      epithelium, although this hypothesis has not been tested experimentally.
      Alternatively, taste buds have been proposed to arise from neuroectodermal cells
      that migrate from peripheral neurogenic sources to the oropharyngeal epithelium
      and give rise to taste bud precursor cells. In order to determine the exact
      embryonic lineage of the cells of vertebrate taste buds, we have employed a
      combination of endogenous and exogenous cell marking techniques to follow
      neuroectodermal and endodermal cells through development. We find, in the
      ambystomatid salamander used in our studies, taste buds arise locally within the
      endodermally-derived epithelium lining the oropharyngeal cavity, and do not
      receive a contribution from neuroectodermal sources, i.e. ectodermal placodes or
      cephalic neural crest.

PMID- 7735850
TI  - Mosaic analysis of the embryonic origin of taste buds.
AB  - The embryonic origins of taste receptor cells have not been established
      experimentally. Although related receptor cells (e.g. hair cells of the inner
      ear, lateral line receptors) are known to arise from neurogenic ectoderm (e.g.
      neural crest or placodes), taste buds are described as arising from local
      epithelial cells. Also unknown is whether or not each taste bud is a clone of
      cells, i.e. arising from a single progenitor. To address these problems, mosaic
      and chimeric analyses of lingual epithelium and taste buds have been undertaken.
      This paper describes the theory of chimeric and mosaic cell lineage analyses, the
      advantages and disadvantages, and the preliminary results obtained from the
      examination of the taste buds and lingual epithelium of: 1) mosaic Xenopus, 2)
      chimeric mice and 3) X-inactivation mosaic mice.

PMID- 7735851
TI  - Desert locusts in Africa: a disaster?
AB  - Migrating locusts, especially the desert locust (Schistocerca gregaria), have
      been feared in Africa for thousands of years as famine-inducing pests. Instead of
      simply waiting for outbreaks to occur, attempts are being made to take preventive
      action against these pests. Since the breeding areas of the desert locust are
      distributed across the entire Sahel region, the Arabian peninsula, Pakistan and
      India, a gigantic logistical and organizational effort is required. Every year,
      millions of dollars are spent on these preventive control measures, which are
      still unable to prevent locust plagues completely. The outbreaks in 1987/88 and
      1993/94 are the most recent examples. Exactly how large potential disasters
      caused by gigantic locust swarms may be and whether the effort and expense
      involved in preventing them pays off economically has never been systematically
      investigated. The Deutsche Gesellschaft fur Technische Zusammenarbeit (GTZ)
      project, 'Integrated Biological Control of Grasshoppers and Locusts', has
      attempted to assess, on the basis of the available data, what the costs and
      potential benefits are and to identify the difficulties involved in developing an
      effective strategy.

PMID- 7735852
TI  - Representing refugees: the role of elites in Burundi refugee society.
AB  - Among Burundi refugees in Tanzania, men who have a university education and know
      English or French are most likely to represent their concerns to officials,
      particularly those from UNHCR. Officials consequently learn about the
      perspectives of refugees from these men. Based upon findings from two years of
      field research in Tanzania, the history of relations between ethnic Hutu elites
      and the peasantry in Burundi is outlined and it is explained why education has
      assumed such pronounced significance in Burundi refugee society. The use of
      ethnicity as a political tool for elite refugees is also described. It is
      concluded that elite refugees may not, as is often claimed, represent the refugee
      majority.

PMID- 7735853
TI  - Nutritional assessments, food security and famine.
AB  - The widely held view that malnutrition is a late indicator of famine is
      challenged on the basis of evidence that people often deliberately reduce their
      food intake as an early response to inadequate food security. This broadens the
      possible interventions in response to high malnutrition rates to include measures
      to support livelihoods under threat of collapse. In the late stages of famine,
      social disruption and distress migration often result in a degraded health
      environment which may raise the threshold of nutritional status associated with
      an increased mortality risk. It is important to assess the underlying causes of
      malnutrition and the associated health risks. At present, the main objective of
      nutrition surveys is usually to obtain a reliable estimate of the prevalence of
      malnutrition among children under five years of age, with little analysis of the
      underlying causes of malnutrition. Experience from the 1984-85 famine in Darfur
      led to the development of an alternative approach to nutritional assessment which
      could be applicable elsewhere in Africa. The combination of quantitative and
      qualitative methods was particularly valuable as a means of gaining a wider and
      deeper understanding of the nature of the nutritional situation.

PMID- 7735854
TI  - Errors in calculating weight-for-height.
AB  - Weight-for-height is widely used as an index of recent malnutrition and often
      forms the basis on which major policy decisions are made about nutrition
      interventions. This article illustrates potential for error in the calculation of
      weight-for-height. Comparisons are made between results obtained using the
      international reference figures published by the World Health Organization, the
      plasticized cards distributed by Teaching-aids At Low Cost and by using the
      computer software package Epi Info (versions 5 and 6). An assessment is made of
      the errors introduced by treating supine measurements incorrectly as stature or
      by treating stature measurements as supine. Comparisons are also made between the
      use of standard deviation scores and percentages of the median. It is recommended
      that the international reference figures be published in a more convenient
      tabular form and that the plasticized cards and percentages of the median should
      not be used for studies involving international comparison. Investigators who
      plan to use Epi Info are advised to take into account the way in which it
      calculates weight-for-height when collecting and analyzing their height
      measurements.

PMID- 7735855
TI  - Injuries associated with floods: the need for an international reporting scheme.

PMID- 7735857
TI  - Damage to urban infrastructure and other public property from the 1989 Loma
      Prieta (California) earthquake.
AB  - This research project investigated the damage to public property caused by the
      1989 Loma Prieta earthquake. The claims filed by state and local governments,
      special districts and non-profit organizations under the Federal Emergency
      Management Agency's (FEMA) disaster assistance program were analyzed to
      understand better the pattern of damage caused by the earthquake. These claims
      accounted for nearly $600 million. The damage distribution was very skewed with
      eleven agencies claiming more than 70 per cent of this total. Non-profit agencies
      accounted for a surprisingly large portion of overall damage. Heavy damage was
      concentrated in relatively few areas. The extent of damage in an area was a
      function of concentration of property, site conditions, characteristics of
      building stock, and distance from the epicenter.

PMID- 7735856
TI  - The European University diploma in international humanitarian aid. ECHO (European
      Community Humanitarian Office).

PMID- 7735858
TI  - Urban household coping strategies during war: Bosnia-Hercegovina.

PMID- 7735859
TI  - Research Committee on Disasters, XIII World Congress of Sociology, Bielefeld,
      Germany, 18-22 July 1994.

PMID- 7735860
TI  - Workshop on "Development in Conflict', Harborne Hall, Birmingham, UK, 1-3
      November 1994.

PMID- 7735861
TI  - Psychological consequences of the 1992 Erzincan (Turkey) earthquake.
AB  - The long-term psychological after-effects of the 1992 Erzincan earthquake are
      examined. 461 subjects from Erzincan were administered a semi-structured
      interview. Emotional distress was measured by a symptom checklist containing 40
      items. 129 subjects from Ankara, the capital of Turkey, were also used as a
      comparison sample. The factor analysis revealed that distress symptoms can be
      grouped into phobic anxiety, somatization, depression and hostility. The
      comparison of the Erzincan and Ankara samples showed that the Erzincan sample had
      higher phobic anxiety scores, the females from Erzincan had higher distress as
      compared to the males from Erzincan and to both males and females from Ankara.
      Regression analyses showed that being female and evaluating one's home as
      insecure against future earthquakes were related to elevated levels of distress.
      Results showed that, even after sixteen months, Erzincan residents had higher
      phobic anxiety and that females seemed to be especially vulnerable to distress.
      Implications of the results for psychosocial intervention are discussed.

PMID- 7735862
TI  - [Eosinophils].
AB  - Although we still do not fully understand many aspects of eosinophil function,
      they are certainly active participants in important physiological and
      pathophysiological events. Eosinophils kill many species of helmints and other
      parasites and probably play a role in defence against infection; they also
      probably play a role in inflammatory responses in the lung, skin and heart. The
      following discussion will review finding that support such conclusions.

PMID- 7735863
TI  - [Applications and aims of molecular biology].
AB  - Clonal studies define the proteic sequence of several allergens leading to the
      recombination and the use of them for immunotherapy extracts. It has been
      possible to clone the receptors for IgE in basophils and mast cells and the
      regulation mechanisms had been delucidated. In a near future it will be possible
      to design recombinant molecules for the specific inhibition of synthesis and
      receptors of IgE and avoid the signal transmissions and the release of mediators.
      The diagnosis of several diseases is based in molecular techniques, inclusive in
      uterus. Genes for various diseases had been cloned in immunology; recombinations
      with gamma interferon had been used for treatment of subjects with atopic
      dermatitis and chronic granulomatous disease.

PMID- 7735864
TI  - [In vitro effect of bacterial extracts of S. aureus in chemokinesis and
      chemotaxis of polymorphonuclear cells].
AB  - The purpose of the study was to determine if the extract of Staphylococcus aureus
      in vitro can modify chemokinesis and induce chemotaxis of polimorphonuclear (PMN)
      cells of peripheral blood in healthy donors. Chemocinesis and chemotaxis of PMN
      of peripheral blood in 30 healthy donors of either sex from 18 to 40 years old
      was measured. A 5 mL sample of peripheral blood was drawn. PMN were separated by
      Boyum's method and challenged with of Staphylococcus aureus extract and C5a as
      chemotactic factors, and Hank's solution chemokinesis. Chemokinesis was 54.6 +/-
      8.8 microns, chemotactic response to C5a was 89 +/- 12.5 microns and with
      bacterial extract the response was 103 +/- 20.1 microns (p). In conclusion,
      complete extract of Staphylococcus aureus stimulates in vitro chemotaxis of PMN
      from healthy donors, and this stimulation is similar to known chemotactic factors
      as C5a.

PMID- 7735865
TI  - Equine parentage testing and DNA technology--the route forward?

PMID- 7735866
TI  - Ultrasound imaging in determining the presence of testicular degeneration in two
      male goats.
AB  - Physical examination and semen evaluation of two infertile goats were indicative
      of testicular degeneration. Ultrasonographically, the testicular parenchyma was
      uncharacteristically heterogeneous with foci of mineralization represented by
      dense hyperechoic areas, many of which showed acoustic shadowing.
      Histopathological examination of the testes post-mortem showed typical
      degenerative changes in the seminiferous tubules, with some affected tubules
      showing evidence of mineralization. The degree of mineralization appeared to
      correlate with the abundance of hyperechoic areas. It was concluded that
      ultrasound imaging can be used as diagnostic technique to confirm the diagnosis
      of testicular degeneration with mineralization.

PMID- 7735867
TI  - A study of mastitis bacteria and herd management practices to identify their
      relationship to high somatic cell counts in bulk tank milk.
AB  - Thirty dairy herds, selected to cover a wide range of bulk tank somatic cell
      count (BTSCC) values, were used to study the relationship between the levels of
      the principal species of mastitis-causing bacteria, herd management practices and
      the BTSCC. A good correlation was found between the number of mastitis
      streptococci (Streptococcus agalactiae, S. dysgalactiae and S. uberis) found in
      bulk tank milk and the BTSCC. Staphylococcus aureus was less significantly
      correlated to BTSCC, but was of increasing importance in borderline BTSCC herds,
      where lower excretion levels into milk were unlikely to trigger hygiene penalties
      and so alert producers to the presence of a significant mastitis problem. High
      BTSCC herds had significantly lower yields and were less likely to use a post
      milking teat dip or to have a regular programme of milking machine maintenance or
      automatic cluster removal. These herds also tended to buy in replacements rather
      than breed their own. Overall the management of high BTSCC herds showed less
      commitment to implementing mastitis control procedures than herds with a
      consistently low BTSCC.

PMID- 7735868
TI  - Response of ponies to adjuvanted EHV-1 whole virus vaccine and challenge with
      virus of the homologous strain.
AB  - Five yearling ponies were vaccinated with inactivated Equid herpesvirus type 1
      (EHV-1) in Freund's complete adjuvant as a double emulsion and revaccinated 6
      weeks later with EHV-1 in Freund's incomplete adjuvant. These ponies and three
      age-matched controls were challenged intra-nasally after a further 6 weeks with
      homologous live virus and monitored clinically, biologically and serologically.
      After challenge, clinical signs were mild in both groups. No cell-associated
      viraemias were detected in vaccinated ponies. Vaccination induced high levels of
      complement-fixing (CF) and virus-neutralizing (VN) antibody, and elicited a
      response to all major viral glycoproteins as shown by western blot analysis.

PMID- 7735869
TI  - Cerebrospinal fluid and plasma glucose concentrations of ovine pregnancy toxaemia
      cases, inappetant ewes and normal ewes during late gestation.
AB  - Cerebrospinal fluid (CSF) and plasma glucose concentrations of spontaneous ovine
      pregnancy toxaemia cases, determined within 24 h of the onset of clinical signs,
      were significantly lower (P < 0.01) compared to inappetant ewes and healthy ewes
      at a similar stage of gestation. A highly significant correlation (P < 0.001, r =
      0.91) was present between the plasma and CSF glucose concentrations when the data
      from the three groups were combined. The data suggest that plasma glucose
      concentration accurately reflects CSF glucose concentration across the range of
      energy states in pregnant ewes and may provide support for the postulate that the
      neurological signs of ovine pregnancy toxaemia result from cerebral
      hypoglycaemia, as reflected by CSF glucose concentration. No cerebral glucose
      estimations were undertaken in this series.

PMID- 7735870
TI  - Vaccination in European salmonid aquaculture: a review of practices and
      prospects.
AB  - Disease control by vaccination is widely used in European salmonid aquaculture
      against vibriosis (Vibrio anguillarum), cold-water vibriosis (Vibrio
      salmonicida), yersiniosis or enteric redmouth disease (Yersinia ruckeri) and
      furunculosis (Aeromonas salmonicida subsp. salmonicida). The vaccines against the
      Vibrio spp. and Y. ruckeri have proven effective especially when administered by
      injection. Furunculosis vaccines have been less successful and have relied on
      combination with potent adjuvants to achieve acceptable protection. Application
      of modern molecular techniques to furunculosis research has delivered a crop of
      experimental vaccines that incorporate purified virulence factors and have shown
      increased protection during challenge. Gene technology has also been used to
      create a defined, nonreverting mutation in a strain of A. salmonicida, which has
      enhanced the feasibility of attenuated live vaccines. The development of
      experimental subunit vaccines against the viral infections and the continued
      advances in the field of immunostimulants, adjuvants and antigen carriers provide
      considerable promise for the future development of commercial vaccines for use in
      salmonid aquaculture.

PMID- 7735871
TI  - 1994--a milk shed year.

PMID- 7735872
TI  - A review of laryngeal paralysis in dogs.
AB  - Laryngeal paralysis is now a frequently recognized disorder, particularly in
      older dogs of certain breeds such as the Labrador retriever, Afghan Hound and
      Irish Setter. The presenting signs may consist of exercise intolerance,
      inspiratory stridor, inspiratory dyspnoea, gagging, coughing and dysphonia. Two
      forms of laryngeal paralysis exist, hereditary and acquired. The hereditary form
      is found in young dogs and transmitted by an autosomal dominant gene. At present
      little is known about the aetiology of acquired laryngeal paralysis and therefore
      treatment is directed at relieving the laryngeal obstruction. Recent reports
      indicate that arytenoid lateralization achieves the best results as a method of
      surgical correction.

PMID- 7735873
TI  - Role of oxytetracycline dihydrate in the treatment of mycoplasma-associated ovine
      keratoconjunctivitis in lambs.
AB  - Thirty-six lambs were placed in two groups of 10 each, one group of 11 and one
      group of five. The first three groups were challenged with a field strain of
      Mycoplasma conjunctivae and the group of five lambs with an inactivated culture.
      One group of lambs was treated with oxytetracycline dihydrate as conjunctivitis
      developed at 1 day post-inoculation (dpi) and the other group was treated when
      the conjunctivitis was at its most severe (3 dpi). A rapid response to treatment
      was observed with a complete recovery obtained after 2 and 4 days, respectively.
      However, the treatment did not eliminate the M. conjunctivae infection.
      Conjunctivitis did not develop in the five lambs challenged with the inactivated
      culture.

PMID- 7735874
TI  - Attachment of Mycoplasma mobile 163 K to piscine gill arches and rakers--light,
      scanning and transmission electron microscopic findings.
AB  - Explant cultures of gill arches and rakers were established to evaluate the
      attachment and colonization characteristics as well as the cytotoxic effects of
      the piscine bacterium, Mycoplasma mobile 163 K on piscine gill epithelium. Light,
      scanning and transmission electron microscopy were applied in this study and
      revealed heavy colonization of mycoplasmas on gill rakers, resulting in severe
      tissue damage of the gill epithelium. The complications for the function of the
      gills during breathing, the mechanisms of cytotoxicity, and the validity of this
      newly-established in vitro model are discussed in detail. In addition, anatomical
      specialities designated as spikes were identified on the inner surface of the
      gill rakers from trout; these could be used in the differentiation of fish.

PMID- 7735875
TI  - The identification of polymorphic microsatellite loci in the horse and their use
      in thoroughbred parentage testing.
AB  - Six new horse microsatellite loci were identified by sequencing M13 clones
      containing horse genomic inserts which gave positive signals when probed with a
      CA/GT repeat probe. Oligonucleotide primer pairs were synthesized for these loci
      and for two previously described horse microsatellites, HTG4 and HTG6. Polymerase
      chain reaction assays were then carried out on a panel of 20 different unrelated
      Thoroughbred horse DNAs. DNAs from eight cases of double covering which could not
      be solved by conventional blood typing were also examined. Several of the loci
      amplified were found to be polymorphic and, using a limited subset of primers, a
      clear exclusion could be established for one of the stallions in five of the
      cases. DNA typing is therefore a useful adjunct to blood typing in the horse and
      indeed, in the future will probably replace it.

PMID- 7735876
TI  - The clinical features of Leber's hereditary optic neuropathy defined by the
      presence of a pathogenic mitochondrial DNA mutation.
AB  - One hundred and seven patients from 79 families were defined as having Leber's
      hereditary optic neuropathy (LHON) by the presence of one of the mitochondrial
      DNA (mtDNA) mutations at positions 11778 (60 families), 3460 (seven families) or
      14484 (12 families). Only half of the 11778 index patients had a history of
      similarly affected relatives; this proportion was higher with the 3460 (71%) and
      14484 (100%) mutations. The ratios of affected male to female patients were 2.5:1
      (11778), 2:1 (3460), and 5.7:1 (14484). Detailed clinical data were available for
      79 patients from 55 families. Visual loss developed between the ages of 11 and 30
      years in 69%, with a range of 6-62 years, and no significant differences between
      mutation groups or males and females. It was bilateral in all but two patients,
      to a median of counting fingers with a central scotoma, developing simultaneously
      in 22% and sequentially in 78%, with a median inter-eye delay of 8 weeks, and
      progressing in each eye over a period of 4-6 weeks. Nineteen patients had pain in
      an affected eye or on eye movements, and four experienced Uhthoff's phenomenon.
      Retinal microangiopathy was uncommon after 6 months from onset and was not
      detected in 36% of patients examined within 3 months of visual loss; the
      microangiopathy was particularly uncommon in the 14484 group. There was no
      difference in the overall visual outcome between the 11778 and 3460 groups with
      median final visual acuities of 1/60 and 3/60, respectively. Particularly severe
      visual loss occurred in one-third of women with the 11778 mutation, to vague
      perception of light or no perception of light in at least one eye. A multiple
      sclerosis-like illness was observed in 45% of females with the 11778 mutation.
      Prognosis was substantially better in the 14484 patients, with recovery to a
      final visual acuity of at least 6/24, in 71% of patients. Good visual outcome was
      strongly correlated with age at onset, all those with onset before 20 years
      having a final visual acuity better than 6/24 as opposed to only 2 out of 6 with
      later onset. Improvement in vision occurred as long as 4 years after onset. High
      alcohol and tobacco consumption, cranial or ocular trauma, young or old age at
      presentation, co-existing neurological disease, and recent childbirth with post
      partum haemorrhage, all contributed to diagnostic difficulties in this series,
      usually in the absence of a family history. These problems were resolved by mtDNA
      analysis.

PMID- 7735877
TI  - Presentation and clinical investigation of mitochondrial respiratory chain
      disease. A study of 51 patients.
AB  - Defects of the mitochondrial respiratory chain are associated with a great
      variety of clinical disorders. Whilst recognition of these conditions is
      increasing, the need for sophisticated biochemical and molecular studies has
      tended to limit both their investigation and diagnosis to a few specialist
      centres. Using a group of 51 patients with histochemically, biochemically and/or
      genetically defined respiratory chain defects, we have examined both the clinical
      heterogeneity of these disorders and how they may be investigated most
      effectively in non-specialist centres. We evaluated the use of the following
      routinely available clinical investigations--fasting intermediary metabolites
      (lactate, pyruvate, ketone bodies, etc.) in blood and cerebrospinal fluid, serum
      creatine kinase estimation, EMG, EEG, CT, MRI and histological/histochemical
      muscle biopsy analysis. Our studies show that, in addition to well-recognized
      syndromes (e.g. chronic progressive external ophthalmoplegia, mitochondrial
      encephalopathy lactic acidosis and stroke like episodes, and myoclonus epilepsy
      with ragged red-fibres, a significant number of patients present with non
      specific encephalopathic disorders. Furthermore, even within those categories of
      respiratory chain disease which have been genetically defined, a wide variation
      of presenting symptoms and signs were found. Where there was initial doubt
      concerning the diagnosis, the following clinical features were helpful in
      suggesting respiratory chain disease: ophthalmoplegia; a maternal pattern of
      inheritance; the presence of myopathy or deafness in association with
      encephalopathy. Of the clinical investigations we assessed, elevated lactate in
      blood or cerebrospinal fluid and low density lesions in the basal ganglia were
      helpful in identifying patients with respiratory chain dysfunction. Histochemical
      analysis of muscle was, however, the single most useful investigation being
      diagnostic in patients with chronic progressive external ophthalmoplegia, Kearns
      Sayre syndrome and myopathy, and of significant importance in patients presenting
      primarily with central nervous system disease. The results of our study are used
      to discuss the most appropriate approach to diagnosis of this group of disorders.

PMID- 7735878
TI  - Long-term follow-up of patients with chronic inflammatory demyelinating
      polyradiculoneuropathy, without and with monoclonal gammopathy.
AB  - We previously demonstrated differences in presentation and initial clinical
      course between patients with idiopathic chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP-I) and those in whom CIDP was associated with a
      monoclonal gammopathy of undetermined significance (CIDP-MGUS). We now report the
      long-term follow-up of 69 patients with CIDP-I and 25 patients with CIDP-MGUS.
      (i) The clinical course was progressive in most of the CIDP-MGUS patients. CIDP-I
      patients were more likely to have a monophasic or relapsing course. (ii)
      Impairment developed more slowly in CIDP-MGUS than CIDP-I patients, with a longer
      time from onset of deterioration to peak impairment for each episode. (iii)
      Patients with CIDP-MGUS experienced less severe functional impairment and a
      lesser degree of measured weakness during their worst episode than did patients
      with CIDP-I. The primary source of functional impairment in many CIDP-MGUS
      patients was sensory. In contrast, the deficits in most patients with CIDP-I were
      primarily motor. (iv) CIDP-MGUS patients experienced a smaller degree of
      improvement to a poorer functional level after each episode than did patients
      with CIDP-I. (v) Most patients had a good outcome. However, the strength and
      functional scores at the time of last follow-up were significantly poorer in CIDP
      MGUS than in CIDP-I patients. (vi) The disease was reclassified in seven
      patients; some patients with CIDP-I developed an MGUS, while some with CIDP-I or
      CIDP-MGUS developed multiple myeloma or a related malignant lymphoproliferative
      disease. These findings have implications for patient counselling and long-term
      prognosis, and underscore the need for long-term clinical and immunological
      monitoring.

PMID- 7735879
TI  - Investigations of the pathogenesis of acquired pendular nystagmus.
AB  - We investigated the pathogenesis of acquired pendular nystagmus (APN) in six
      patients, three of whom had multiple sclerosis. First, we tested the hypothesis
      that the oscillations of APN are due to a delay in visual feedback secondary, for
      example, to demyelination of the optic nerves. We manipulated the latency to
      onset of visually guided eye movements using an electronic technique that induces
      sinusoidal oscillations in normal subjects. This manipulation did not change the
      characteristics of the APN, but did superimpose lower-frequency oscillations
      similar to those induced in normal subjects. These results are consistent with
      current models for smooth (non-saccadic) eye movements, which predict that
      prolongation of visual feedback could not account for the high-frequency
      oscillations that often characterize APN. Secondly, we attempted to determine
      whether an increase in the gain of the visually-enhanced vestibulo-ocular reflex
      (VOR), produced by viewing a near target, was accompanied by a commensurate
      increase in the amplitude of APN. Increases in horizontal or vertical VOR gain
      during near viewing occurred in four patients, but only two of them showed a
      parallel increase in APN amplitude. On the other hand, APN amplitude decreased
      during viewing of the near target in the two patients who showed no change in VOR
      gain. Taken together, these data suggest that neither delayed visual feedback nor
      a disorder of central vestibular mechanisms is primarily responsible for APN.
      More likely, these ocular oscillations are produced by abnormalities of internal
      feedback circuits, such as the reciprocal connections between brainstem nuclei
      and cerebellum.

PMID- 7735880
TI  - Regional cerebral blood flow during a self-paced sequential finger opposition
      task in patients with cerebellar degeneration.
AB  - The brain regions controlling self-paced sequential finger movements in patients
      with cerebellar degeneration were studied by measuring changes in regional
      cerebral blood flow (rCBF) in eight patients using bolus injections of H2(15)O
      and PET. The results were compared with those obtained in eight normal age
      matched control subjects. Patients and control subjects performed a self-paced
      sequential finger opposition task with the right hand, completing a sequence of
      movements every 4-6 s. Both groups had strong increases in the adjusted rCBF
      contralaterally in the primary motor cortex (M1) and ventral premotor area (PMv),
      in the caudal supplementary motor area (SMA) and cingulate motor area (CMA), and
      bilaterally in the prefrontal cortex (PFC), the lobus parietalis inferior (LPI),
      putamen and cerebellum. The cerebellum, PMv, rostral CMA, PFC and LPI were more
      active in the control subjects than in the patients, and the M1, SMA, caudal CMA
      and putamen were more active in the patients than in the control subjects. The
      reduced activity of the cerebellar neurons in the patients produced a complex
      pattern of rCBF increases and decreases in other brain regions. Our results
      suggest that for the preparation and execution of sequential finger movements,
      patients with cerebellar degeneration use a medial premotor system, including the
      SMA and caudal CMA, as well as the M1 and putamen, rather than the PMv, PFC, LPI
      and rostral CMA.

PMID- 7735881
TI  - Intramodal somaesthetic recognition disorders following right and left hemisphere
      damage.
AB  - A dissociation between apperceptive and associative processing after right and
      left hemisphere damage, respectively, has been suggested for visual, auditory and
      visuo-tactile matching tasks. This study was aimed at testing for this
      dissociation in a purely somaesthetic task. Forty consecutive patients with
      recent right and left hemispheric vascular lesions and 10 normal controls were
      studied. The groups were compared on two intramodal somaesthetic matching tasks,
      consisting of either meaningless shapes (apperceptive recognition) or meaningful
      objects (associative recognition). In normal controls, no significant difference
      was found either between the two tests, indicating a similar degree of
      difficulty, or between hands. An analysis of variance indicated a differential
      impairment of the two hemisphere-damaged groups on the two tests in comparison
      with normal controls. Right hemisphere lesions impaired the apperceptive, but not
      the associative, task, while the reverse occurred after left hemisphere lesions.
      This double dissociation between side of hemispheric lesion (right and left) and
      level of recognition impairment (apperceptive and associative) extends the
      results reported for other sensory modalities to intramodal tactile recognition
      matching.

PMID- 7735882
TI  - Brain systems for encoding and retrieval of auditory-verbal memory. An in vivo
      study in humans.
AB  - Long-term auditory-verbal memory comprises, at a neuropsychological level, a
      number of distinct cognitive processes. In the present study we determined the
      brain systems engaged during encoding (experiment 1) and retrieval (experiment 2)
      of episodic auditory-verbal material. In the separate experiments, PET
      measurements of regional cerebral blood flow (rCBF), an index of neural activity,
      were performed in normal volunteers during either the encoding or the retrieval
      of paired word associates. In experiment 1, a dual task interference paradigm was
      used to isolate areas involved in episodic encoding from those which would be
      concurrently activated by other cognitive processes associated with the
      presentation of paired associates, notably priming. In experiment 2, we used the
      cued retrieval of paired associates from episodic or from semantic memory in
      order to isolate the neural correlates of episodic memories. Encoding of episodic
      memory was associated with activation of the left prefrontal cortex and the
      retrosplenial area of the cingulate cortex, while retrieval from episodic memory
      was associated with activation of the precuneus bilaterally and of the right
      prefrontal cortex. These results are compatible with the patterns of activation
      reported in a previous PET memory experiment in which encoding and retrieval were
      studied concurrently. They also indicate that separate brain systems are engaged
      during the encoding and retrieval phases of episodic auditory-verbal memory.
      Retrieval from episodic memory engages a different, but overlapping, system to
      that engaged by retrieval from semantic memory, a finding that lends functional
      anatomical support to this neuropsychological distinction.

PMID- 7735883
TI  - Dichotic listening in patients with partial section of the corpus callosum.
AB  - Patients with a complete section of the corpus callosum have been observed to
      exhibit strong left-ear suppression when different speech stimuli are presented
      to both ears simultaneously (so-called dichotic listening). Data concerning the
      locus of corpus callosum damage that causes strong left-ear suppression remains
      scanty. In the present investigation, a consonant-vowel syllable dichotic
      listening test was given to five right-handed patients with partial sections of
      the corpus callosum, which were located using MRI and accurately defined
      measurement procedures. The following two measurement methods were used: (i) the
      genu-splenium (G-S) method, in which a lesion was localized in the
      anteroposterior dimension relative to the total length of the corpus callosum,
      defined as the distance between the most anterior point of the genu to the most
      posterior point of the splenium; and (ii) the rostrum-splenium (R-S) method,
      which takes into account the curvature of the corpus callosum, and in which a
      lesion was localized relative to the total length of the corpus callosum, defined
      as the length of the curved line from the tip of the rostrum to the end of the
      splenium. Results were compared with scores from 50 normal control subjects.
      Strong left-ear suppression was observed in two patients, who had surgical
      sections of the posterior 15.5-18.5% of the corpus callosum as measured with the
      G-S method, or the posterior 20-24% of the corpus callosum as measured with the R
      S method. The suppression phenomenon persisted for more than 10 years post
      surgery. On the other hand, the remaining three patients, who had lesions
      anterior to the posterior 17-28% of the corpus callosum as measured with the G-S
      method or 20-33% as measured with the R-S method exhibited no left-ear
      extinction. Despite the common assumption that damage to the posterior part of
      the trunk of the corpus callosum causes strong left-ear suppression, the results
      from the G-S method indicated that damage to the splenium defined as the
      posterior one-fifth of the segment between the anterior-most and posterior-most
      points of the corpus callosum, cause strong left-ear suppression. By the R-S
      method, results showed that damage to the splenium (the posterior one-fifth of
      the curvature of the corpus callosum) and possibly the part extending to the most
      posterior part of the trunk (the posterior one-quarter of the curvature) causes
      strong left-ear suppression.

PMID- 7735884
TI  - Inhibitory and excitatory interhemispheric transfers between motor cortical areas
      in normal humans and patients with abnormalities of the corpus callosum.
AB  - Transcranial magnetic stimulation of the motor cortex was performed in 10 normal
      subjects and 10 patients with radiographical abnormalities of the corpus
      callosum. Seven patients had a complete or partial agenesis or hypoplasia of the
      corpus callosum, two had a thin corpus callosum due to hydrocephalus or white
      matter degeneration and one had a circumscript contusion lesion of the corpus
      callosum. The patients served as a clinical model to investigate transcallosal
      influences on excitatory and inhibitory effects of motor cortex stimulation and
      to assess the potential diagnostic use of interhemispheric conduction studies and
      the contribution of interhemispheric interaction on transcranially elicited
      contralateral excitatory and inhibitory motor responses. Stimulation over one
      motor cortex suppressed tonic voluntary electromyographic activity in ipsilateral
      hand muscles in all subjects with preserved anterior half of the trunk of the
      corpus callosum. Since this suppression was lacking or had a delayed onset
      latency in patients with absence or abnormalities of the anterior half of the
      trunk of the corpus callosum it can be concluded that it is due to a
      transcallosal inhibition (Ti) of the opposite motor cortex mediated by fibres
      passing through this part of the corpus callosum. In normal subjects Ti had an
      mean onset latency of 36.1 +/- 3.5 ms (SD) and a duration of 24.5 +/- 3.9 ms. The
      calculated mean transcallosal conduction time was 13 ms. The threshold of Ti
      recorded in muscles ipsilateral to stimulation tended to be higher than the one
      for eliciting excitatory contralateral motor responses (56 +/- 6% versus 46 +/-
      10% maximum stimulator output). Cortical thresholds (at rest) for contralateral
      excitatory hand motor responses were higher in patients with developmental
      abnormalities of the corpus callosum than in normals (66 +/- 17% versus 46 +/-
      10% maximum stimulator output), which probably reflects also a facilitatory
      transcallosal interaction of both motor cortices in normals. In contrast,
      facilitation of cortically elicited motor responses in one hand by strong
      contraction of the other hand was the same in the patients with agenesis of the
      corpus callosum and normals, which suggests that this facilitatory spread takes
      place on a spinal rather than on a cortical level. Central motor latencies and
      amplitudes of contralateral hand motor responses were the same in patients with
      developmental abnormalities of the corpus callosum and normals (6.1 +/- 0.7 ms
      versus 6.3 +/- 0.7 ms and 6.7 +/- 2.4 mV versus 6.6 +/- 2.9 mV) so that callosal
      transfers do not seem to influence corticospinal conduction properties.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7735885
TI  - Distributed representations of semantic knowledge in the brain.
AB  - Category-specific language impairments have been postulated to require the
      existence of an explicit category organization within semantic memory. However,
      it may be possible to demonstrate analytically that this is not necessary. We
      hypothesize that category-specific organization can emerge from perceptual,
      functional, and associative feature information about objects that is maintained
      in order to process language. In this paper, we conduct several experiments to
      test the computational validity of this hypothesis. Physical objects were encoded
      in terms of semantic features, based on basic perceptual and motor modalities and
      higher level knowledge of function, for use in artificial neural networks.
      Mathematical methods were used to analyse the encodings and the neural networks.
      The results demonstrate the emergence of semantic categories in the networks,
      although such information was not preprogrammed. We conclude that category
      specific language organization can emerge from the inherent nature of semantic
      features themselves, and does not require special internal categorical
      organization of semantic memory.

PMID- 7735886
TI  - Cross-over, completion and confabulation in unilateral spatial neglect.
AB  - Patients with left-sided neglect generally mis-bisect horizontal lines to the
      right of mid-position. However, with short lines they frequently cross over and
      place their marks to the left; a phenomenon not easily explained by current
      theories of neglect. It is difficult to ascertain whether patients neglect the
      ipsilateral segment of short lines, perceptually distort these lines, or extend
      these lines leftward at a representational level. Reading horizontally arrayed
      letter strings is an alternative task potentially capable of sorting between
      these hypotheses, providing this task could be demonstrated to be comparable to
      line bisections. In this study, we exploit the observation that line bisection
      performance may be described by a power function: psi = K phi beta, in which psi
      represents the subjective awareness of lines and the objective measurements of
      these lines. The constant and exponent are empirically derived. We have
      investigated whether reading task performance also subscribes to power functions.
      Five patients with left-sided neglect were tested on line bisections and reading
      tasks with stimuli of varying horizontal lengths. Performance on both tasks could
      be described by power functions and patients were similarly ordered by severity
      across both tasks. Since power function analyses established that these tasks
      were comparable, reading performance on short words provided insight into how
      patients bisected short lines. Patients reported additional letters to the left
      end of short words suggesting that cross-over bisections are analogously a
      consequence of completion or confabulation of short lines beyond their objective
      left end-point. Although most neglect patients have difficulties forming
      veridical left-sided representations, this cross-over phenomenon is interpreted
      as resulting from a lack of inhibition of leftward confabulatory mental
      representations. Since both bisections and reading tasks are described by a
      continuous function, it is proposed that similar lack of inhibition must also be
      present, albeit hidden, when patients confront stimuli with longer lateral
      extension. Confabulatory phenomena at the left edge of these patients'
      rightwardly constricted attentional window, may be far more common than hitherto
      appreciated.

PMID- 7735887
TI  - Spatial hemineglect in back space.
AB  - The subjective location of the mid-sagittal plane was assessed by a free-field
      auditory localization task in the front and in the back half-spaces in 11 right
      brain-damaged patients with spatial hemineglect, 10 right brain-damaged patients
      without spatial hemineglect, and 11 normal control subjects. In patients with
      hemineglect the subjective mid-sagittal plane was found to be displaced
      rightwards in both half-spaces. Both patients without hemineglect and controls,
      in contrast, made a minor error, and showed a greater displacement towards the
      left side in the back half-space. In four right brain-damaged patients the
      rightward displacement was confined either to the front, or to the back half
      space. This pattern of impairment may be explained by a rightward, ipsilesional,
      pathological translation of an egocentric co-ordinate system, rather than by a
      rotation around the vertical axis of the body.

PMID- 7735888
TI  - Auditory and visual sensory representations in human prefrontal cortex as
      revealed by stimulus-evoked spike-wave complexes.
AB  - Multimodal sensory properties of the prefrontal cortex have been extensively
      studied in monkeys, while little is known of such functions in humans. We report
      electrophysiological evidence for auditory and visual representations in the
      dorsolateral prefrontal cortex, as inferred from intracerebral 'depth' recordings
      of focal, sensory-evoked spike-wave complexes (SWC) in an epileptic patient. In
      addition to clinical monitoring, the patient participated in behavioural evoked
      potential studies involving auditory and visual discrimination tasks. Inspection
      of evoked potential recordings from different medial-to-lateral prefrontal sites
      revealed overlapping, but non-identical topographies of evoked SWC for the two
      sensory modalities. The maximal activity of sensory-evoked SWC was located 7 mm
      more medially for visual than for auditory stimuli, and occurred later for visual
      presentations (mean = 117 ms following stimulus onset) than for auditory ones
      (mean = 87 ms). Effects of sensory habituation were seen. Evoked SWC were less
      likely to occur following repeated presentations of an unchanging tone than when
      tones alternated in pitch, or when a tone followed an omission in stimulus
      presentation. Visual hemifield effects were found, with greater prefrontal
      responsiveness to presentations in the contralateral visual hemifield. These
      results are consistent with electrophysiological findings in animals indicating
      overlapping auditory and visual representations in the dorsolateral prefrontal
      cortex.

PMID- 7735889
TI  - Motion imagery in Parkinson's disease.
AB  - Patients with Parkinson's disease fail to fully profit from advance information
      about a target's movement in tracking tasks, possibly indicating deficient
      anticipation of the target's movement. Time estimation has been claimed to be
      deficient in Parkinson's disease. On the background of these studies, we tested
      the hypothesis that motion imagery is impaired in Parkinson's disease. Eleven non
      demented patients with Parkinson's disease and nine age-matched controls
      participated in experiments testing their ability to anticipate trajectories of
      moving points (prediction whether two moving points would crash or not) and to
      estimate the time needed for completion of an invisible target's movement (a
      point moving around a circle). In addition, mirror drawing, a task involving
      motor learning and adjustment of movement to incongruent visual feedback, was
      tested. The Parkinson's disease patients, who failed to improve on mirror
      drawing, were not impaired on the imagery tasks: they estimated movement time and
      predicted trajectories with equal precision as the controls. Motion imagery thus
      appears to be intact in Parkinson's disease. However, Parkinson's disease
      patients did not accelerate their predictions of trajectories with practice as
      fast as the controls, a deficit which may be interpreted in terms of the fronto
      striatal dysfunction repeatedly demonstrated in Parkinson's disease.

PMID- 7735890
TI  - Abnormal muscle coactivation patterns during isometric torque generation at the
      elbow and shoulder in hemiparetic subjects.
AB  - To study abnormal spatial patterns of muscle activation in hemiparetic stroke, we
      compared EMG activity in paretic and contralateral elbow and shoulder muscles of
      10 hemiparetic subjects during 1.5-s voluntary isometric contractions, against
      five to eight different loads. Isometric forces were generated in eight
      directions, referenced to a plane orthogonal to the long axis of the forearm, and
      were recorded by a three degrees of freedom load cell, mounted at the wrist.
      Surface and intramuscular EMGs of six elbow and six shoulder muscles were
      recorded from both impaired and contralateral upper extremities of each subject.
      The spatial characteristics of EMG activation of individual muscles were
      summarized using two measures. The first, called the 'net resultant EMG vector'
      is a new measure which calculated the vector sum of EMG magnitudes for each of
      the eight directions, and the second, index of EMG focus, is a measure of the
      range of EMG activation recorded for each load level. Use of these measures
      permitted us to describe spatial EMG characteristics quantitatively, which has
      not been done previously. We observed consistent and statistically significant
      shifts in the resultant EMG vector directions in the impaired limb, especially in
      shoulder and other proximal muscles. Significant increases in the angular range
      of EMG activity were also identified and were most evident at the elbow.
      Correlation analysis techniques were used to assess the degree of coactivation of
      different muscle pairs. There were consistent EMG coactivation patterns observed
      across all subjects (both normal and hemiparetic). However, in spasticparetic
      limbs, additional novel coactivational relationships were also recorded,
      especially between elbow flexors/shoulder abductors and elbow extensors/shoulder
      adductors. These novel coactivation patterns represent a reduction in the number
      of possible muscle combinations, or in the number of possible 'synergies' in the
      paretic limb of the stroke subject. This reduction in number of 'synergies' could
      result from a loss of descending command options; from an increased reliance on
      residual, descending brainstem pathways (such as the reticulospinal and
      vestibulospinal projections); from changes in spinal interneuronal excitability;
      or from a combination of several of these factors. The relative merits of these
      hypotheses are addressed.

PMID- 7735891
TI  - Physiological study of cervical dystonia. Task-specific abnormality in contingent
      negative variation.
AB  - To investigate the pathophysiology of dystonia, we recorded contingent negative
      variation (CNV) in 12 patients with cervical dystonia and in 12 age-matched
      normal subjects. In a simple reaction time paradigm, the subjects were given a
      pair of a warning stimulus and a subsequent stimulus that triggered head rotation
      to either side or extension of the fingers. In normal subjects, CNVs for head
      rotation were not affected by neck muscle pre-activation simulating torticollis,
      and were always symmetrical with equally high amplitudes over the frontal and
      central leads. By contrast, CNVs for finger movement had the maximum over the
      central lead and showed a characteristic distribution; those for the right finger
      movement had the left hemisphere dominance, whereas those for the left finger
      movement had similar amplitudes over both hemispheres. In patients with rotatory
      torticollis (rotatocollis), the components of CNVs for head rotation were
      markedly attenuated in all the leads, except for the initial negative deflection
      (orienting response). As a whole, cervical dystonia patients had significantly
      lower amplitudes of late CNVs for head rotation than normal subjects (P < 0.001),
      whereas late CNV amplitudes in finger extension did not differ in the two groups.
      Their reaction times for head rotation were similar, but durations of EMG
      activities were prolonged in the patients because of co-contractions of the
      antagonists. The task-specific CNV amplitude loss is therefore not explained by
      reaction times or by the abnormal neck muscle activities prior to the movement,
      but it reflects a failure of neural activities preparing for a phasic neck
      movement, resulting in co-contraction of the agonists and the antagonist.
      Dystonia may be associated with defective retrieval or retaining of specific
      motor programmes or subroutines in response to sensory stimuli.

PMID- 7735892
TI  - Pericranial muscle hardness in tension-type headache. A non-invasive measurement
      method and its clinical application.
AB  - Using a new method to measure the hardness of pericranial muscles, the role of
      muscle factors in tension-type headache was evaluated. In 223 normal healthy
      subjects, the hardness of trapezius muscles was 82 +/- 15 kPa/cm (mean +/- SD).
      The muscle hardness in women, 92 +/- 17 kPa/cm, was significantly greater than
      that in men, 74 +/- 14 kPa/cm (P < 0.01). Trapezius muscles were significantly
      harder than paraspinal posterior neck muscles measured at the level of the fifth
      cervical vertebra (71 +/- 13 kPa/cm; n = 26) but a significant correlation in
      muscle hardness did exist between these two muscle groups (r = 0.89, P < 0.001).
      Muscle hardness did not show a significant correlation with advancing age, blood
      pressure or subjective feeling of stiffness in the shoulder. A significant
      correlation was noted between the muscle hardness measured by the present method
      and the stiffness scores evaluated by manual palpation. In patients with tension
      type headache (n = 60), the hardness of trapezius muscles, 114 +/- 24 kPa/cm
      (mean +/- SD), was significantly greater than that in normal subjects (P < 0.01).
      Twenty-six patients (43% of the total) showed significantly high values which
      exceeded the mean +/- 2 SD (113 kPa/cm) of the normal value, while the remaining
      patients (57%) constituted a high normal group. The hardness of posterior neck
      muscles measured in 27 patients (99 +/- 21 kPa/cm) was also significantly greater
      than that in normal subjects (P < 0.01). There was no significant difference in
      muscle hardness between episodic tension-type headache and chronic tension-type
      headache.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735893
TI  - Botulinum toxin-induced myopathy in the rat.
AB  - We have used histological and histochemical techniques at the light microscopical
      level, and electron microscopy to examine the myopathological changes in rat
      muscle up to 30 weeks following botulinum toxin injection. Apart from muscle
      fibre atrophy and related myofibrillar structural changes, the results show a
      number of striking abnormalities which developed and disappeared at different
      stages. During the first 4 weeks after toxin injection, vacuoles of variable size
      were seen in the sarcoplasm near myonuclei, both at and away from endplates.
      Following this, between 4 and 10 weeks post-injection, progressive degeneration
      of junctional folds and separation of some nerve terminals from the simplified
      postsynaptic membranes were observed. At different time points following recovery
      from the toxin-induced paralysis (evidenced by the increase in muscle fibre size
      and return of function) a number of abnormalities were still detectable in muscle
      fibres. These included the appearance within them of multiple arrays of
      sarcotubular profiles, focal areas lacking myofibrillar organization and
      mitochondria, abnormal mitochondrial aggregates showing crystalline inclusions,
      and extension of the postsynaptic densities along the full depth of junctional
      folds. Furthermore, targetoid-like areas were detected histochemically following
      recovery from the toxin-induced paralysis. The early extensive vacuolation of the
      sarcoplasm and the degeneration of junctional folds suggest a myotoxic effect of
      botulinum toxin. The late changes are likely to be (at least in part) related to
      the process of recovery following reinnervation.

PMID- 7735894
TI  - The skeletal muscle sodium and chloride channel diseases.
AB  - The cause of several familial muscular diseases have recently been linked to
      mutations within skeletal muscle sodium and chloride channel genes. Thomsen's and
      Becker's diseases are autosomal dominant and recessive, respectively, and are
      caused by at least seven different mutations in the CLCN1 (ClC-1) skeletal muscle
      chloride channel gene on chromosome 7q35. Hyperkalaemic periodic paralysis,
      paramyotonia congenita and a small heterogeneous group of related 'pure'
      myotonias are autosomal dominant disorders and are due to at least 16 different
      mutations in the SCN4A (SkM1) adult skeletal muscle sodium channel gene on
      chromosome 17q23-25. There is generally little correlation between the position
      of a mutation in the channel and the phenotype. Indeed, identical sodium channel
      mutations in unrelated subjects and sometimes in different members of the same
      family can have different clinical expressions. It seems, however, that mutations
      of the inactivation gate (ID3-4 loop) of the sodium channel tend to produce
      paramyotonia or pure, sometimes severe, myotonia and respond most favourably to
      the same medications (tocainide and mexiletine). The structure and polarity of
      substituted amino acids at a mutation site, especially in highly evolutionally
      conserved regions of the gene, are undoubtedly important to the expression of a
      channel disease and may partly explain phenotypic variability. In addition,
      genetic polymorphisms elsewhere, either in the gene or other channel-related
      loci, and the net effect of other types of muscle ion channels on the electrical
      potential of the plasma membrane probably contribute to disease expression.

PMID- 7735895
TI  - Properties and biogenesis of peroxisomes.
AB  - Many species of monocellular eukaryots as well as the majority of animal cell and
      plant tissues show the presence of peroxisomes or microperoxisomes. Their size,
      shape and internal organization may differ in various cellular types
      significantly. Typical components of animal cell peroxisomes are the membrane,
      matrix, low density compartment enriched in lipids, and the compartment
      containing D-amino acid oxidase. The group of four enzymes (catalase, D-amino
      acid oxidase, L-alpha-OH-acid oxidase) the location of which had been originally
      discovered in peroxisomes of hepatocytes of rodents was later widened by
      approximately forty further enzymes. It is though probable that evolution brought
      along a reduction and loss of various metabolic functions of peroxisomes and a
      decrease in the number of enzymes. Peroxisomes are characterized by high
      variability of the enzymatic content in dependence on the nutritional conditions
      and the effect of xenobiotics. Fasting, diabetes mellitus, high-lipid diet,
      peroxisome proliferators induce several peroxisomal enzymes, especially fatty
      acids beta-oxidation. The mechanism of the impact of heterogeneous substances on
      the gene transcription has been clarified recently. Substances as fibrates,
      retinoic acid, polyunsaturated fatty acids activate specific types of receptors
      PPAR (peroxisome proliferators activated receptors) belonging to the superfamily
      of receptors activated by steroid hormones, thyroid hormones, and D-vitamins. A
      simultaneous induction of several peroxisomal enzymes can be achieved by the
      linkage between PPAR and specific areas of promotors of particular genes. Such
      areas-PPREs (peroxisomal proliferator response elements) with five repeated
      TGA(A/C/T)CT hexanucleotide sequences separated by one nucleotide were discovered
      in several peroxisomal genes. It is assumed that the stimulation of transcription
      can be achieved by the linkage between homodimers, and heterodimers of nuclear
      receptors on these DNA sections. The majority of peroxisomal proteins is
      synthesised in the cytoplasm, namely on polysomes being in matured forms.
      Unimpaired biogenesis of peroxisomes requires membrane transport proteins and
      presence of signal in polypeptide chain of imported proteins (PTS-peroxisomal
      targeting signal). The function of PTS in many peroxisomal proteins is fulfilled
      by the C-terminal tripeptide which is composed of amino acids, namely serine,
      lysine, and leucine (SKL-tripeptide), respectively by a tripeptide with a very
      similar composition in amino acids. Aside from this signal, still another signal
      exists, which is located at the N-end of peroxisomal proteins. The role of
      membrane proteins 70, 35, 256, 22, 15 kDa, is being discussed in relationship to
      the functions and diseases caused by impaired biogenesis of peroxisomes. (Fig. 4,
      Ref. 128.)

PMID- 7735896
TI  - [The effect of preoperative diagnostic methods on the correct selection of
      operative procedure on the thyroid gland].
AB  - The study compares three diagnostic procedures, the analysis of which is aimed at
      a choosing the optimal extent of resection on the thyroid. Diagnostic procedures,
      when based on clinical examination (palpation, scintigraphy, laryngoscopy, X
      ray), lead to the optimal extent of resection in 74.2% of patients. Procedures
      selection performed on the basis of fine-needle aspiration cytology (FNAC)
      results lead to the correct extent of resection in 93.1% of patients. The
      procedures of frozen section lead to the correct resection extent in 81.3% of
      patients. (Tab. 1, Fig. 1, Ref. 25.)

PMID- 7735897
TI  - [The antioxidant defense system and trace elements].
AB  - The survey presents current knowledge on antioxidant defence systems and on the
      role and meaning of trace elements in these systems. From this point of view the
      most important elements include transient metal iron and copper, and there after
      selenium, zinc and manganese. They represent essential components of antioxidant
      enzymes or transport proteins which participate in intermediation of antioxidant
      reactions of ceruloplasmin, SOD, GSPx, and catalase. Both deficiency, and in some
      cases also excess of mentioned trace elements may contribute to oxidative stress.
      (Tab. 3, Fig. 3, Ref. 27.)

PMID- 7735898
TI  - Comparative study of the mammalian liver innervation: an immunohistochemical
      study of protein gene product 9.5, dopamine beta-hydroxylase and tyrosine
      hydroxylase.
AB  - The liver innervation of eight different mammalian species was examined by
      immunohistochemical localization of protein gene product (PGP) 9.5 to visualize
      the general innervation for autonomic nerve fibres. In addition, dopamine beta
      hydroxylase (DBH) and tyrosine hydroxylase (TH), two enzymes involved in
      catecholamine synthesis, were localized immunohistochemically to delineate
      hepatic sympathetic nerve fibres. We found that: (1) Within the interlobular
      region of each species, PGP 9.5, DBH and TH-positive nerve fibres were all seen
      in close association with branches of hepatic arteries, portal veins and bile
      ducts. (2) Within the parenchyma of the guinea-pig, cat, dog, pig, monkey and
      human liver, the presence of the three immuno-positive nerve fibres could be
      unequivocally identified, although the density of these intralobular fibres
      showed marked species variation. Moreover, immunoelectron microscopic study
      confirmed that PGP 9.5-positive nerve terminals of the human liver are in close
      apposition to hepatocytes. (3) In mouse and rat, no parenchymal nerve fibres
      immunoreactive for PGP 9.5, TH or DBH could be demonstrated.

PMID- 7735899
TI  - Mandibular bone fluoride accumulation in wild red deer (Cervus elaphus L.) of
      known age.
AB  - Mandibular bone fluoride concentration and its relation to age were studied in a
      sample of 39 red deer of known age (between 2 and 18 years) from an area not
      exposed to increased fluoride deposition (Harz mountains, Germany). Bone fluoride
      level ranged from 208 to 1026 ppm dry weight and was positively correlated with
      age (r = 0.808, P < 0.001), the rate of skeletal fluoride accumulation being
      higher in younger individuals. This indicates that during the period of skeletal
      growth, fluoride uptake is more rapid than in later life when accumulation at a
      lower rate occurs during normal bone turnover. Bone fluoride levels found in the
      present sample are regarded as resulting from "normal" fluoride exposure in a
      recent central European red deer population.

PMID- 7735900
TI  - Heat stress causes excessive drinking in fed and food deprived pregnant goats.
AB  - Water intake was studied in six goats during late pregnancy to investigate if
      heat stress induces primary polydipsia. The goats were fed twice daily or
      deprived of food for 24 hr to avoid postprandial drinking and induce
      hyponatremia. Signs of stress was evaluated by determination of plasma cortisol
      concentration. Ambient temperature was increased from 20 degrees C to 38.0-39.5
      degrees C for 5.15 hr. Water temperature was 35 +/- 1 degree C during heat
      stress. Fed goats started to drink 13 +/- 3 min after the heaters were turned on
      and water diuresis developed in five of them. The body weight increased
      simultaneously with decreased plasma Na concentration and osmolality showing that
      the goats also stored water. During food deprivation, plasma Na concentration and
      osmolality fell, and plasma aldosterone concentration increased. Despite
      hyponatremia, food deprived goats started to drink 44 +/- 15 min after the
      heaters were turned on and then they drank repeatedly. Three of them underwent
      water diuresis. Hemodilution was observed both in fed and food-deprived goats
      during heat stress. These results show that heat stress induced primary
      polydipsia in pregnant goats. It is suggested that stimulating signals from
      warmth receptors overrode inhibiting influences from receptors signalling
      hyponatremia and hypoosmolality at the "thirst center" in the hypothalamus. Heat
      stress did not increase plasma cortisol concentration, but catching sight of food
      caused an abrupt, short-lasting elevation.

PMID- 7735901
TI  - Organic osmolytes in the kidney of domesticated red deer, Cervus elaphus.
AB  - The cortex, inner and outer medulla, and papilla of kidneys of domestic red deer
      were analysed. In hydrated animals the urine concentration was found to be 672 +/
      45 mOsm.l-1. The medullary and papillary regions of the kidney were rich in the
      osmolytes betaine, glycerophosphorylcholine (GPC), inositol and sorbitol, all of
      which showed a steep rise in concentration from cortex to papilla. The kidney was
      rich in free amino acids, in particular taurine, glutamate (+glutamine), glycine
      and alanine, which were present at concentrations sufficient to suggest a
      possible role as osmolytes.

PMID- 7735903
TI  - Metabolic rates and thermal conductance in four species of neotropical bats
      roosting in hot caves.
AB  - Data are presented on metabolic rates and thermal conductance for four species of
      neotropical bats, Pteronotus quadridens, Mormoops blainvillii (Mormoopidae),
      Monophyllus redmani and Erophylla bombifrons (Phyllostomidae). Each of these bats
      predominantly or exclusively roosts in hot caves (28-40 degrees C) in Puerto
      Rico. Basal metabolic rates (BMR) for these four species were 55%, 48%, 66%, and
      66% of values expected from the Kleiber curve, respectively. Thermal conductance
      was 93%, 55%, 175%, and 158% of values expected from the Aschoff curve,
      respectively. These data indicate that, in addition to food habits, variation in
      BMR is highly correlated to roost microclimate. Pteronotus and Mormoops, like
      other insectivorous species, have low BMRs. The low BMR of the nectar/fruit
      eating Monophyllus and Erophylla, as well as the low termal conductance in
      Mormoops, is consistent with their habit of roosting in hot caves, suggesting
      that roost microclimate is an important selective force in the physiological
      adaptation of these bats.

PMID- 7735902
TI  - Changes of intracellular electrolyte contents in rat skeletal muscle during body
      suspension.
AB  - The CNS-mediated inhibition of active Na(+)-K+ transport in both "type S" muscle,
      soleus (SOL), and "type FF" muscle, extensor digitorum longus (EDL) was
      investigated in rats suspended horizontally. Plasma Na+ and K+ contents did not
      change during the suspension period. The relative wet weight of SOL decreased
      more than that of EDL by suspension. There was significant intracellular Na+
      accumulation and K+ loss in both SOL and diaphragm of suspended rats. However,
      cerebrum, cerebellum, medulla oblongate, ventricle, liver, pancreas, kidney,
      intestine, aorta and EDL were spared from the intracellular Na+ accumulation and
      K+ loss. Sciatic nerve sectioning or cervical spinal cord transection recovered
      the Na+ and K+ contents in the SOL of suspended rats. The results indicate the
      existence of neural inhibition of the active Na(+)-K+ transport in skeletal
      muscle of the suspended rats.

PMID- 7735904
TI  - Maturational differences in coronary flow and interstitial transudate adenosine
      during alteration of perfusate oxygenation in isolated rabbit hearts.
AB  - This study was designed to investigate effects of perfusate oxygenation and
      maturation on coronary flow (CF), interstitial transudate adenosine (ITA) and
      coronary effluent adenosine (CEA) in isolated rabbit hearts. Hearts were paced at
      a fixed rate and were perfused under constant pressure at two different levels of
      perfusate oxygenation: baseline (B) (pO2 = 408 +/- 7 mmHg, O2 content = 1.28 +/-
      0.03 ml O2/dl) and a lower level (L) (pO2 = 189 +/- 4 mmHg, O2 content = 0.59 +/-
      0.02 ml O2/dl). CF was higher in immature (I, age 5 weeks) compared with mature
      (M, age 12 weeks) hearts at both levels of perfusate oxygenation (9.7 +/- 0.4 vs.
      7.7 +/- 0.3 and 12.9 +/- 0.4 vs. 9.2 +/- 0.3 ml/min/g). I hearts had
      correspondingly higher values for myocardial oxygen consumption (MVO2) (53 +/- 3
      vs. 49 +/- 2 and 39 +/- 3 vs. 35 +/- 2 microL O2/min/g), but similar values for
      venous oxygen tensions (nuO2) (240 +/- 9 vs. 219 +/- 10 and 74 +/- 4 vs. 62 +/- 3
      mmHg), compared with M hearts at B and L. Although interstitial transudate
      adenosine (ITA) concentration was similar in I and M hearts at B (409 +/- 75 vs.
      254 +/- 39 nM), it was lower in I than M hearts at L (2500 +/- 770 vs. 4210 +/-
      1000 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735905
TI  - Plasma insulin and glucagon responses to acute challenges of acetate, propionate,
      n-butyrate and glucose in growing gilts (Sus scrofa).
AB  - A supraphysiological dose (2.5 mmol kg-1 body weight) of acetate, propionate, n
      butyrate or glucose was intravenously injected to measure plasma insulin and
      glucagon responses in growing gilts. Plasma insulin concentrations remained
      constant after injection of the volatile fatty acids. Plasma glucagon
      concentrations increased (P < 0.05) after n-butyrate injection following an
      initial temporary decrease (P < 0.05), and showed a similar tendency after
      acetate or propionate injection. These results suggest that a supraphysiological
      dose of acetate, propionate or n-butyrate may stimulate a plasma glucagon
      response in growing piglets.

PMID- 7735906
TI  - Neurotransmitter and neuropeptide modulation of high affinity choline uptake in
      Limulus brain.
AB  - The role of neurotransmitters in the modulation of the sodium-dependent high
      affinity choline uptake system (HAChUS) of the horseshoe crab, Limulus polyphemus
      has been investigated utilizing a tissue slice preparation. Choline uptake was
      significantly decreased by carbachol but unaffected by atropine and d
      tubocurarine. The muscarinic agonist oxotremorine decreased choline uptake by
      30.4% while the muscarinic antagonist, pirenzepine, increased uptake by 29.6%.
      Applied in combination, pirenzepine and oxotremorine abolished their individual
      effects resulting in control values for choline uptake. The non-cholinergic
      transmitters octopamine and serotonin significantly enhanced choline uptake. The
      neuropeptide proctolin elicited a 20% increase in choline transport whereas Phe
      Met-Arg-Phe (FMRF) amide was without effect. This study demonstrates that
      neurotransmitters and neuropeptides modulate the HAChUS, possibly through
      specific receptor-mediated second messenger systems.

PMID- 7735907
TI  - Food intake, nutrient utilization and water turnover in the lesser mouse-deer
      (Tragulus javanicus) given lundai (Sapium baccatum).
AB  - Voluntary food intake, digestibility and water turnover were determined in adult
      Malaysian lesser mouse-deer (Tragulus javanicus) given unlimited access to lundai
      foliage (Sapium baccatum). Daily dry matter (DM) intake was 42.4 g/kg metabolic
      live mass (M0.73) or 3.7% M. Digestible energy intake was 853 kJ/day (571 kJ
      metabolisable energy per M0.73), calculated to be used with 79% efficiency.
      Apparent digestibility (%) of organic matter was 83.8, crude fibre 63.7, acid
      detergent fibre 60.5, neutral detergent fibre 72.1 and crude protein 65.0.
      Urinary excretion of the purine derivative, allantoin, was 0.05 mg/g digestible
      DM intake suggesting rumen microbial yield efficiency may be lower than in other
      ruminant species. Total water intake was 182 ml/M0.82. The body-water content of
      the fed mouse-deer, from tritiated water dilution, was 77% M, consistent with a
      very lean carcass. Turnover of body water was 17% per day. The mouse-deer
      produced relatively dry, well-defined faecal pellets.

PMID- 7735908
TI  - Pharmacological characterization of the N-methyl-D-aspartate (NMDA) receptor
      recognition site in porcine cerebral cortical membranes using [3H]-CGP 39653.
AB  - The high-affinity NMDA receptor competitive antagonist [3H]-CGP 39653 binds to
      Triton X-100 (0.04%) treated porcine cerebral cortex membranes in a saturable and
      reversible manner, with a KD of 6.1 +/- 0.97 nM and a Bmax of 944 +/- 55 fmol/mg
      protein. Association of ligand with the recognition site was rapid (estimated k1
      = 1.1 x 10(7) M-1 min-1), and a steady state was reached within 30 min of
      incubation at 4 degrees C. Dissociation was also rapid (estimated k-1 = 0.2 min
      1). The pharmacology of the binding site was similar to that for the rat brain,
      with mean pIC50 values (Hill slopes in parentheses, *indicating significant
      difference from unity) of 7.54 (0.51*), 6.99 (0.68*), 6.98 (0.71), 6.63 (0.80*),
      6.31 (0.62*) and 5.17 (0.78) for R-CPP, L-glutamate, CGS 19755, cis-2,4
      methanoglutamate, L-aspartate and NMDA, respectively. Other compounds (glycine,
      MK-801, kainate, S-AMPA and magnesium ions), previously observed not to interact
      competitively with the NMDA binding recognition site, showed a low affinity for
      the porcine cerebral cortex [3H]-CGP 39653 binding site. It is concluded that the
      pharmacological properties of the NMDA receptor recognition site labelled by [3H]
      CGP 39653 are similar in the pig and rat cerebral cortices.

PMID- 7735909
TI  - Empty bladder and dehydrated pelvic patch water uptake in Bufo marinus:
      inhibition by captopril.
AB  - Dehydration (10.3 +/- 2.2%, N = 7) caused a significant increase in pelvic patch
      water uptake (Jv) from 875 +/- 86 (N = 21) to 2130 +/- 150 (N = 21) cm3.cm-2 x
      10(-7), while the pectoral Jv increased from 258 +/- 31 (N = 21) to 545 +/- 75 (N
      = 21 cm3.cm-2 x 10(-7). Captopril inhibited the pelvic patch Jv in empty bladder
      toads decreasing the Jv from 978 +/- 45 (N = 27) to 607 +/- 38 (N = 27) cm3.cm-2
      x 10(-7). In dehydrated toads (15 +/- 2%, N = 14), captopril reduced the pelvic
      patch Jv from 1807 +/- 213 (N = 21) to 957 +/- 91 (N = 21) cm3.cm-2 x 10(-7).
      Captopril injection decreased the blood pressure in dehydrated toads from 25.6 +/
      1.9 (N = 21) to 16.9 +/- 1.5 (N = 21) mmHg with no change in heart rate.

PMID- 7735910
TI  - Cholecystokinin does not act on the efferent pathway of cholinergic and
      adrenergic nerves to inhibit ruminal contractions in sheep (Ovis aries).
AB  - The effect of exogenous cholecystokinin-octapeptide (CCK-8) on ruminal
      contractions and the role of efferent pathways of cholinergic and adrenergic
      nerves on the effect were studied in sheep. Intravenous infusion of CCK-8 at 11.4
      and 45.6 pmol/kg/min significantly inhibited the frequency and amplitude of
      ruminal contractions in conscious sheep. After bilateral cervical vagotomy,
      intravenous infusion of CCK-8 at 45.6 mol/kg/min had no detectable effect on
      amplitude of ruminal contractions induced by electric stimulation to the cervical
      vagus nerve (1 msec, 20 Hz, 5 mA, for 10 sec at 1-min intervals) in anesthetized
      sheep. The amplitude of contractile responses of ovine ruminal muscle strips to
      acetylcholine at 5 x 10(-5) M was not inhibited by CCK-8 applied simultaneously
      at 1 x 10(-9) M. Intravenous infusion of phentolamine at 53.0 nmol/kg/min,
      propranolol at 101.4 nmol/kg/min, or their combined infusion did not alter the
      inhibitory action of CCK-8 at either dose on ruminal contractions in conscious
      sheep. These results suggest that CCK-8, which does not act on the efferent
      pathway of cholinergic and adrenergic nerves, may reflexively inhibit
      reticuloruminal contractions via vagal afferent fibers in sheep.

PMID- 7735911
TI  - Effects of alpha-adrenoceptor agonists and antagonists on metabolic rate in
      cattle.
AB  - Brahman steers (Bos indicus) were treated with the alpha 2-adrenergic agonists,
      guanfacin.HCl (4-440 micrograms/kg), UK14304.HCl (20-125 micrograms/kg) and
      clonidine.HCl (0.2-5 micrograms/kg). All three agonists produced dose-dependent
      reductions in metabolic rate, heart rate and rectal temperature (P < 0.001).
      Brahman heifers were infused with idazoxan.HCl (10 micrograms/kg/hr), an alpha 2
      adrenergic antagonist, alone and in combination with an intramuscular injection
      of guanfacin.HCl (80 micrograms/kg). Idazoxan alone did not alter rectal
      temperature but it blocked the guanfacin-induced lowering of rectal temperature
      (P = 0.05 for the interaction between the two drugs). Idazoxan alone raised
      metabolic rate (P = 0.01). Guanfacin lowered metabolic rate (P = 0.007) and heart
      rate (P = 0.03), but the blocking of the guanfacin effect by idazoxan could not
      be demonstrated (P > 0.05) for either. The same heifers treated with 0.5, 1.0 and
      5 micrograms/kg prazosin.HCl, an alpha 1-adrenergic antagonist, had significant
      changes in metabolic rate (P = 0.003) and heart rate (P = 0.008) at 0.5 and 5
      micrograms/kg. Metabolic rate and heart rate decreased at the lower dose and
      increased at the higher dose. These results with cattle parallel previous results
      in rats (Gazzola, 1993) where a minimal, conceptual model for the partial control
      of resting metabolic rate by the sympathetic nervous system was postulated. The
      model indicates points of control in the sympathetic nervous system which could
      be manipulated so as to alter the metabolic rate of farm animals.

PMID- 7735912
TI  - Analysis of the kinetics and voltage-dependency of transient and delayed K+
      currents in muscle fibers isolated from the flatworm Schistosoma mansoni.
AB  - There are two distinct voltage-dependent K+ currents in muscle fibers freshly
      isolated from the human flatworm parasite S. mansoni. Present is a delayed
      rectifier current with a tau act of 17 msec and tau inact > 3 sec. The delayed
      rectifier is very resistant to steady-state inactivation, with over 40% of the
      current non-inactivating, and over 15 sec required for the maximum inactivation
      of the other portion. The current is resistant to block by extracellular
      tetraethylammonium, is half-blocked by 10 mM 4-aminopyridine, and is insensitive
      to dendrotoxin. Also present is an "A" current with tau act < 1 msec and tau
      inact < 15 msec. The "A" current, like the delayed rectifier current, is
      resistant to block by external tetraethylammonium and is insensitive to
      dendrotoxin. Three micromoles of 4-aminopyridine produce a half-blockade of the
      "A" current. These two K+ currents are very similar to a delayed rectifier and
      "A" currents that have been described in a number of lower and more advanced
      animals.

PMID- 7735913
TI  - Noradrenaline-induced hypothermia is suppressed in the vagotomized cold-exposed
      pigeon.
AB  - Vagotomized (VX) pigeons studied 2 days after surgery exhibited a significant
      decrease in cloacal temperature (Tb) and respiratory rate (Rf), and an increase
      in heart rate (Hf) and metabolic rate (M) at the thermoneutral zone, when
      compared with sham-operated (SVX) pigeons. The effect of intravenous
      noradrenaline (NA) on Tb, Rf, Hf and M was examined in SVX and VX-pigeons at 15
      degrees C. Following NA administration, the Tb and Rf in the SVX-birds dropped
      from the preinjection level, but in VX-pigeons, they were not significantly
      altered. In SVX-pigeons, a total suppression of shivering was apparent following
      NA-injection, while in the majority of VX-pigeons, shivering was only slightly
      affected or even increased. The Hf in both SVX- and VX-birds increased following
      NA-injection. The responses to reserpine were qualitatively similar to NA,
      although much slower. There were no differences between SVX- and VX-birds with
      regard to Tb, M and Rf following acetylcholine (ACh) and eserine (Ese) injection.
      Hf increased after ACh+Ese administration in SVX-pigeons, but in VX-birds, it
      decreased after an initial surge. Shivering was suppressed for 18-20 min in SVX
      birds and 30-50 min in VX-birds. It is suggested that the lack of the hypothermic
      effect of NA in VX-birds is due to the maintenance of oxygen uptake with
      unimpaired capacity for shivering.

PMID- 7735914
TI  - The JIM interview. David Korn, MD.
AB  - When David Korn, MD, was named dean of the Stanford University School of Medicine
      on October 9, 1984, he assumed leadership of a world class research institution.
      Stanford was at the forefront of medicine in the areas of transplantation and
      oncology, and the steady influx of privately insured patients had generated a net
      operating surplus of $17 million in that year alone. However, in the same issue
      of the Stanford University Hospital newsletter which announced the selection of
      Korn as Dean, a small article appeared on a new prospective payment system based
      on diagnosis-related groups (DRGs). The article stated that the new system had
      begun smoothly, though some payments for cost outliers had been delayed. Other
      cost containment measures soon followed, most notably the implementation of
      managed care, and by 1990, Stanford was $14 million in the red. Buffeted by
      changes in medical reimbursement, competition with less costly hospitals, and a
      nasty squabble with Congress over indirect research costs, Stanford has been on
      the frontlines of a struggle now confronting many academic medical centers. After
      successfully consolidating the university's clinical services into a unified
      Stanford Health System, Korn announced that he would be stepping down as Dean on
      April 1. Interviewed in his office in Palo Alto, Korn reflected on the
      difficulties of dealing with managed care, the current financial state of the
      institution, and what Stanford's experience may predict for other academic
      medical centers.

PMID- 7735915
TI  - Regulation of endothelial cell gap formation and paracellular permeability.
AB  - Investigation of the regulation of permeability properties of the endothelium has
      yielded evidence to support the concept of a dual regulation of EC gap formation
      and barrier function. In this model, the primary determinants of EC permeability
      are tethering/adhesive properties (Figure 1) and tensile centripetal force
      generation (Figure 2). The importance of actin-myosin interactions and active
      cellular contraction and force generation has been reviewed. In the model of
      thrombin-induced EC barrier dysfunction, there is a strong shift in the MLC
      species from the unphosphorylated to the diphosphorylated form, indicating
      activation of MLCK, a key enzyme whose importance in EC contraction has been well
      established. Although important differences between EC and SMC exist, endothelial
      cell gap formation involves actomyosin-dependent contractile mechanisms similar
      to SMC, a cellular system in which MLC phosphorylation correlates with the
      initial rate of tension development. The increase in MLC phosphorylation and
      isometric tension is consistent with the hypothesis that activation of signal
      transduction mediates an increase in isometric tension to a new level of "latch
      state" through the cytoskeleton. Thus, the available evidence implicates a strong
      role for cellular force generation and contraction in the evolution of thrombin
      induced barrier dysfunction. Accumulating evidence also indicates that modulation
      of tethering properties, primarily those involving cell-matrix and cell-cell
      adhesion, is also a key determinant of basal EC barrier properties as well as
      agonist-mediated barrier dysfunction. Because each of these focal adhesion
      constituents may be involved in establishing tethering properties in endothelium,
      they each may be involved in determining barrier permeability and may be involved
      in the evolution of agonist-mediated barrier dysfunction. Therefore, in addition
      to MLCK-dependent active tensile force generation, agonist-induced barrier
      dysfunction may occur via MLCK-independent pathways that rely on basal levels of
      MLC phosphorylation or by affecting proteins involved in tethering properties of
      endothelium that contribute to barrier function. Further examination of tethering
      force properties, combined with elucidation of EC relaxation via MLC
      dephosphorylation may yield clues as to how this important vascular barrier is
      maintained and restored after vascular insult.

PMID- 7735916
TI  - Bone marrow transplantation--current concepts.

PMID- 7735917
TI  - Risk adjustment for medical effectiveness research: an overview of conceptual and
      methodological considerations.

PMID- 7735918
TI  - Immunization with vesicular stomatitis virus nucleocapsid protein induces
      autoantibodies to the 60 kD Ro ribonucleoprotein particle.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder of
      unknown etiology that is characterized by antibodies binding ribonucleoprotein
      complexes. The epitopes of SLE associated 60 kd Ro (or SSA) autoantigen share
      sequence with vesicular stomatitis virus (VSV) nucleocapsid (N) protein and SLE
      patients with anti-Ro are more likely to bind the N-protein than anti-Ro negative
      patients. METHOD: We immunized New Zealand white (NZW) rabbits with purified VSV
      N-protein to examine the relationship between the immune response to N-protein
      and anti-Ro. RESULTS: After multiple immunizations with VSV N-protein, NZW
      rabbits produced not only IgG antibodies to VSV N-protein but also an autoimmune
      response to Ro antigen. The IgG fraction of the rabbit immune serum precipitates
      60 kd Ro protein as well as its associated Y RNAs. Antibodies elicited by 10
      immunizations of VSV N-protein bind to at least 20 linear epitope groups on VSV N
      protein and over 25 linear epitope groups on 60 kd Ro protein. These antibodies
      also bound 5 of the 6 shared sequences between 60 kd Ro protein and VSV N
      protein. CONCLUSIONS: Our data demonstrate that an immune response initiated
      towards a foreign antigen, selected on the basis of sharing short sequence
      similarity with the autoantigenic epitopes of an autoantigen, can lead to an
      autoimmune response.

PMID- 7735919
TI  - A diagnostic assay for the Wiskott-Aldrich syndrome and its variant forms.
AB  - BACKGROUND: The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease
      characterized by severe thrombocytopenia, eczema, and impaired immunity. While
      the diagnosis is usually straightforward, the syndrome may be expressed in an
      attenuated form, a phenotype which is difficult to distinguish from other types
      of congenital thrombocytopenia. Although a molecular-based assay for diagnosis of
      the spectrum of WAS patients has not been available, recent data indicate that
      WAS is associated with a specific profile of impaired mitogen responsiveness and
      suggest that detection of this abnormality may provide a diagnostic marker for
      all forms of the disease. To address this issue, we have studied patients with
      classical and atypical WAS for their lymphocyte proliferative responses to four T
      cell mitogenic stimuli and compared their response patterns to those detected in
      unaffected children. METHODS: Clinical histories and informed consent were
      obtained from 23 patients with either classical or putative (ie, atypical) WAS,
      16 subjects with other disorders, and 12 healthy children. Peripheral blood
      mononuclear cells (PBMCs) collected from patients and controls were resuspended
      in culture medium, stimulated with the T cell mitogens phytohemagglutinin (PHA),
      concanavalin A (Con A), neuraminidase/galactose oxidase (NAGO), or periodate, and
      cultured for 60 h in 0.2 mL aliquots. Following a 20 h pulse with 3H-thymidine,
      cultures were harvested and the 3H-thymidine uptake was evaluated by liquid
      scintillation counting. RESULTS: The most striking observation involved response
      to periodate. While lymphocytes from all healthy control children proliferated in
      response to periodate treatment, cells from both classical as well as atypical
      WAS patients consistently failed to proliferate in response to this mitogen. By
      contrast, lymphocyte proliferative responses to PHA, Con A, and NAGO were
      detected in all patients and controls, although responses generally were lower in
      cells from classical WAS patients compared to other children. In two WAS
      patients, bone marrow transplantation and clinical improvement were associated
      with a change from no periodate response (pre-transplant) to periodate
      responsiveness (post-transplant). In contrast to the WAS patients, cells from
      patients with other hematologic and primary immune deficiency diseases responded
      uniformly to all four mitogens, including periodate. CONCLUSIONS: The data
      presented here indicate that T cells from patients with either classical or
      attenuated WAS fail to undergo proliferation in response to periodate, an agent
      that induced extensive T cell mitogenesis of cells from all healthy controls as
      well as patients with diseases other than WAS. As the WAS patients' cells did
      proliferate in response to treatment with other T cell mitogens, it appears that
      periodate induced T cell proliferation is selectively impaired in WAS and that
      detection of this defect may be of value in the distinction of both classical and
      attenuated WAS from other thrombocytopenic conditions.

PMID- 7735920
TI  - Effect of H2-receptor antagonists on bile acid metabolism.
AB  - BACKGROUND: Several reports have been presented concerning pronounced overgrowth
      of bacteria in gastric juices of patients treated with H2-receptor antagonists.
      However, there has been no report concerning influence of H2-receptor antagonists
      on jejunal flora. Thus, to investigate the influence and its effect on bile acid
      metabolism, this study was performed: 1) to examine whether patients with gastric
      ulcers who have been treated with H2-receptor antagonists have positive bile acid
      breath tests due to bacterial overgrowth in their jejuna; 2) to verify that these
      bacteria, isolated and identified, have deconjugation ability; and 3) to
      determine whether the changes in the gastric pH are related to bacterial
      overgrowth. METHODS: The methods used were detection of deconjugation of bile
      acids in early phase by a bile acid breath test using 5 muCi of oral glycine-1
      14C labeled glycocholate, aspiration of jejunal fluids by a double lumen tube
      with a rubber cover on the tip, and examination of deconjugation ability by thin
      layer chromatography. RESULTS: Expired breath samples from all 18 patients after
      administration of H2-receptor antagonists showed a significant increase in 14CO2
      specific activity compared with those before administration of H2-receptor
      antagonist and the normal controls, and bacterial overgrowth was found in the
      jejunal fluid of the patients after administration of H2-receptor antagonist. The
      administration of tetracycline to the 18 patients reduced the 14CO2 specific
      activity significantly. The following species were identified in the jejunal
      fluid samples obtained from the patients: Escherichia coli, Candida albicans,
      Pseudomonas aeruginosa, enterococcus, Lactobacillus bifidus, Bacteroides
      vulgatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Eubacterium
      lentum, and Eubacterium parvum. All of the species identified except for
      Escherichia coli, Pseudomonas aeruginosa, and Candida albicans deconjugated bile
      acids. There were significant correlations between the 14CO2 activity and gastric
      pH before and after administration of H2-receptor antagonist, respectively.
      CONCLUSIONS: Patients with gastric ulcers who were treated with H2-receptor
      antagonists have increased bile acid deconjugation due to bacterial overgrowth in
      their jejuna containing species that can deconjugate bile acids. The bacterial
      overgrowth is probably associated with a shift to neutral pH in the gastric juice
      caused by the H2-receptor antagonists.

PMID- 7735921
TI  - Restriction isotyping of apolipoprotein E R145C in type III hyperlipoproteinemia.
AB  - BACKGROUND: An adolescent female who presented with type III hyperlipoproteinemia
      was found to have an E3/2 phenotype by isoelectric focusing while restriction
      isotyping using HhaI revealed a pattern compatible with classical E3/3. Studies
      were carried out to determine the nature of the patient's apolipoprotein E
      abnormality. METHODS: A 244 bp fragment of exon 4 of apolipoprotein E was
      amplified by the polymerase chain reaction (PCR). Restriction isotyping was
      carried out with BbvI and Fnu4HI and results were confirmed by direct sequencing.
      RESULTS: The patient was found to be heterozygous for a C-->T transition at the
      first base of codon 145, resulting in a substitution of cysteine for arginine
      (R145C) which completely explained the discrepancy between the isoelectric
      focusing and HhaI restriction isotyping. We noted that the DNA change altered
      palindromic recognition sites for the endonucleases BbvI and Fnu4HI. CONCLUSIONS:
      Digestion with BbvI or Fnu4HI allows for rapid restriction isotyping for the rare
      apolipoprotein E R145C mutation associated with hyperlipidemia.

PMID- 7735922
TI  - 6th International Symposium on Helicobacter pylori and its Diseases. Tokyo,
      Japan, 16-17 September 1993.

PMID- 7735925
TI  - Non-steroidal anti-inflammatory drugs associated with gastroduodenal injury and
      Helicobacter pylori.
AB  - OBJECTIVE: To clarify the relationship between non-steroidal anti-inflammatory
      drug (NSAID)-associated gastroduodenal mucosal injury and Helicobacter pylori
      infection. DESIGN AND METHODS: The incidence of H. pylori infection was
      determined in a group of patients treated with NSAID for rheumatoid arthritis for
      > or = 3 months and in a control group of patients with mainly abdominal symptoms
      but without rheumatoid arthritis and not being treated with NSAID. The incidence
      of H. pylori infection was also determined in patients treated with different
      NSAID and antirheumatic drugs. In addition, the minimum inhibitory concentration
      of several NSAID against H. pylori was investigated. RESULTS: The incidence of H.
      pylori infection in the NSAID group tended to be lower than in the control group,
      and was significantly lower in patients with gastric ulcers. The incidence of
      infection did not differ between patients treated with one or with more than one
      NSAID. Differences in the infection rate were found between individual NSAID,
      with indomethacin being associated with a particularly low rate. No differences
      in the infection rate were found between different antirheumatic drugs. The
      minimum inhibitory concentration of ibuprofen was low. CONCLUSION: H. pylori
      appears to have little effect on gastroduodenal mucosal injury associated with
      long-term NSAID administration.

PMID- 7735923
TI  - Helicobacter pylori infection in Japan: current status and future options.
AB  - BACKGROUND: The combination of the high prevalence of Helicobacter pylori
      infection in Japan and the availability of methods to diagnose and treat the
      infection suggest that elimination of the infection from the population might be
      beneficial. Therefore we reviewed the epidemiology, consequences and possible
      benefits of elimination of H. pylori in Japan. RESULTS: H. pylori infection has
      been etiologically linked to peptic ulcer disease, gastric carcinoma and gastric
      B-cell lymphoma. The cumulative risk of those with H. pylori infection for
      developing peptic ulcer disease is 15-20%, with 0.01-0.1% developing gastric
      carcinoma. Twenty to thirty per cent of those infected suffer mortality or
      morbidity related to H. pylori infection. Recommendations were made concerning
      the elimination of this infection. CONCLUSIONS: Eradication of H. pylori should
      largely eliminate peptic ulcer disease with all its costs and complications,
      while rapidly changing the risk of developing gastric cancer.

PMID- 7735924
TI  - Pharmacological effects of metronidazole+tetracycline+bismuth subcitrate versus
      omeprazole+amoxycillin+bismuth subcitrate in Helicobacter pylori-related
      gastritis and peptic ulcer disease.
AB  - PURPOSE: Two 4-week triple-therapy treatment regimens,
      metronidazole+tetracycline+bismuth subcitrate and omeprazole+amoxycillin+bismuth
      subcitrate, were compared in a randomly allocated double-blind trial for their
      efficacy in eradicating Helicobacter pylori from the gastric mucosa of patients
      with gastritis and/or peptic ulcer disease. PATIENTS AND METHODS: The presence of
      gastritis and/or peptic ulcers was confirmed by endoscopy in all patients
      included in the study. To evaluate drug effects, we used the urease test on
      gastric mucosa, and haematoxylin-eosin and specific Giemsa stains on biopsy
      tissues obtained by endoscopic procedures; we also evaluated the improvement in
      clinical symptoms before and after the 4-week treatments. RESULTS: Among 164
      patients with gastritis and/or peptic ulcers, H. pylori infection was confirmed
      in 93.9% (154 patients) by the urease test and in 87.8% (144 patients) by
      haematoxylin-eosin stain. Following 4 weeks of treatment with both combination
      regimens, negative conversion rates by the urease test and haematoxylin-eosin
      staining and rates of recovery from clinical symptoms were similar in both
      regimens (metronidazole+tetracycline+bismuth subcitrate: 82.3, 72.9 and 73.9%;
      omeprazole+amoxycillin+bismuth subcitrate: 89.6, 83.4 and 76.1%, respectively).
      Also, the extent of inflammatory activity and the H. pylori score by the Giemsa
      method indicated high rates of recovery, with improvements to grade 0 (lowest
      grade) from higher grades with both combination regimens (60.4 and 66.7% of
      patients taking metronidazole+tetracycline+bismuth subcitrate and 64.6 and 83.3
      of those taking omeprazole+amoxycillin+bismuth subcitrate). However, the
      prevalence of side effects during the 4 weeks of treatment was doubled in the
      former group compared to the latter (25.5 versus 12.5% of patients). CONCLUSIONS:
      Significant improvements in biochemical and histopathological findings and in the
      clinical symptoms of gastritis and/or peptic ulcer disease in patients with a
      high rate of H. pylori infection were observed equally with both regimens.
      However, there were notably fewer side effects in patients treated with
      omeprazole+amoxycillin+bismuth subcitrate. We therefore recommended this regimen
      in preference to metronidazole+tetracycline+bismuth subcitrate for the treatment
      of H. pylori-related gastritis and peptic ulcer disease.

PMID- 7735926
TI  - Are there ulcerogenic strains of Helicobacter pylori?
AB  - AIM: To outline the evidence for and against ulcerogenic strains of Helicobacter
      pylori. CONTROVERSY: Although H. pylori is now well established as a predisposing
      factor in peptic ulcer disease the question of why only a minority of people
      infected with H. pylori develop peptic ulceration remains unanswered and is the
      subject of much controversy. COMMON VIEW: Perhaps the most accepted view to date
      is the belief that there are ulcerogenic strains of H. pylori which produce a
      specific cytotoxin responsible for the ulceration. CONCLUSION: At the present
      time the case for ulcerogenic strains is not proven and the differences between
      H. pylori infected peptic ulcer patients and H. pylori infected non-ulcer
      subjects may relate simply to host factors.

PMID- 7735927
TI  - Eradication of Helicobacter pylori.
AB  - PURPOSE: To critically review current indications and therapies for Helicobacter
      pylori eradication. DATA IDENTIFICATION: Studies selected for this review were
      identified from Medline and a manual search of the literature. RESULTS OF DATA
      ANALYSIS: The clearest indication for H. pylori eradication is in the treatment
      of H. pylori-positive duodenal and gastric ulcer since eradication of the
      infection prevents ulcer relapse, effectively curing the disease. The use of anti
      H. pylori therapy in non-ulcer dyspepsia remains controversial and further
      studies are required. Despite strong circumstantial evidence linking H. pylori
      and gastric cancer, it is premature to advocate H. pylori therapy for primary
      prevention of neoplasia. Triple therapy (bismuth, metronidazole, tetracycline)
      can eradicate H. pylori in over 90% of cases but this multidrug regimen is not
      ideal because of side effects, possible non-compliance and doubtful efficacy
      against metronidazole-resistant infection. Proton-pump inhibitor-antibiotic
      combinations are a promising alternative to triple therapy with few side effects
      and good compliance, but there is uncertainty about the most effective
      combination. H. pylori reinfection after successful eradication is unusual (< 1%
      per year). CONCLUSIONS: H. pylori eradication is now the treatment of choice in
      H. pylori-positive peptic ulcer disease. The search continues for the ideal H.
      pylori treatment regimen which will combine high efficacy, safety and patient
      acceptability, with low cost.

PMID- 7735928
TI  - Effects of anti-ulcer agents on antibiotic activity against Helicobacter pylori.
AB  - OBJECTIVE: To investigate the mechanism of action of a series of potential
      combination therapies for use against Helicobacter pylori. DESIGN: The effects of
      certain anti-ulcer agents on the antimicrobial activity of antibiotics effective
      against H. pylori were determined in vitro. METHODS: H. pylori was cultured on
      Skirrow's agar. Amoxycillin, clarithromycin, erythromycin and tetracycline were
      used. The anti-ulcer agents studied comprised aluminum chloride, sofalcone [2'
      carboxymethyl 4,4'-bis(3-methyl-2-butenyloxy)chalcone] and zinc chloride. Urease
      activity was measured by the urease-indophenol method. The minimum inhibitory
      concentration was determined by a plating method, with H. pylori streaked on
      plates containing various concentrations of the antibiotics plus sublethal doses
      of the anti-ulcer agents. RESULTS: This in vitro study showed that sofalcone had
      a direct antibacterial effect and, in addition, inhibited the adhesive property
      of H. pylori. It did not inhibit the antimicrobial activity of the antibiotics
      amoxycillin, clarithromycin, erythromycin or tetracycline against H. pylori. The
      metal ions had inhibitory effects on the antimicrobial activity of amoxycillin,
      erythromycin and tetracycline, but not on that of clarithromycin. CONCLUSION:
      This study suggests that sofalcone is a suitable candidate for combination
      therapy.

PMID- 7735929
TI  - Combination therapy with clarithromycin and sofalcone for eradication of
      Helicobacter pylori.
AB  - OBJECTIVE: To clarify the efficacy of combination therapy with clarithromycin and
      sofalcone for eradication of Helicobacter pylori. DESIGNS: We studied 42 patients
      with H. pylori-positive gastroduodenal diseases, who were divided into two groups
      according to treatment period. Group 1 comprised 27 patients (seven with gastric
      ulcers, 14 with duodenal ulcers and six with gastritis) treated with a
      combination of clarithromycin (200 mg, three times a day) + sofalcone (100 mg,
      three times a day) for 3 weeks. Group 2 comprised 15 patients with chronic active
      gastritis treated with the same doses of clarithromycin + sofalcone but for only
      2 weeks (group 2). The H. pylori status of all patients was assessed by culture,
      rapid urease test and histological examination at the end of treatment and 4
      weeks after the end of treatment. The gastritis score, the index of intracellular
      periodic acid-Schiff-positive substance in the antral mucosa and the ammonia
      concentration in gastric secretions were also estimated before and after
      treatment. RESULTS: In group 1, with over half the patients excluded from the
      follow-up, H. pylori was eradicated in nine out of 13 patients (69.2%) compared
      with six out of the complete group of 15 (40.0%) patients in group 2, without
      serious side effects. In these patients, significant improvements were seen in
      the gastritis score (P < 0.025), the index of periodic acid-Schiff-positive
      substances in the antral mucosa (P < 0.025) and the ammonia concentration in
      gastric secretions (P < 0.02) after treatment. CONCLUSION: These results suggest
      that modification of the treatment regimen is needed, with higher doses of
      clarithromycin and combination therapy with proton-pump inhibition.

PMID- 7735930
TI  - Characteristics of vacuolating toxin produced by Helicobacter pylori.
AB  - OBJECTIVE: We sought a good indicator cell line to use in detecting the
      vacuolating toxin produced by Helicobacter pylori and in examining the
      characteristics of the toxin. DESIGN AND METHODS: Using five cell lines [baby
      hamster kidney (BHK-21), human amnion (FL), human uterine cancer (HeLa), rabbit
      kidney (RK-13) and African green monkey kidney (Vero)], cytotoxicity assays were
      performed with 33 H. pylori strains. To analyse the proteins produced by
      toxigenic and non-toxigenic strains, immunoblotting was done with the sera of
      patients with gastroduodenal diseases. RESULTS: When RK-13, FL, Vero, BHK-21 and
      HeLa cells were used for the assay, 73, 61, 27, 27 and 21% of strains,
      respectively, were toxigenic. The vacuolating toxin is sensitive to heat at 70
      degrees C. By immunoblot analysis, under non-denaturing conditions, immune sera
      recognized proteins with molecular weights of 600,000 and 500,000 in the
      toxigenic but not in the non-toxigenic strains. CONCLUSION: H. pylori produces
      vacuolating toxin, which is a heat-sensitive protein at 70 degrees C and is
      easily detectable by cytotoxicity assay using the RK-13 cell line. Toxigenic H.
      pylori strains produce various proteins, including this toxin, which are
      recognized by sera from patients with gastroduodenal diseases.

PMID- 7735931
TI  - Vacuolating cytotoxin production by Helicobacter pylori isolates from peptic
      ulcer, atrophic gastritis and gastric carcinoma patients.
AB  - OBJECTIVE: We investigated the production of vacuolating cytotoxin by
      Helicobacter pylori isolates from patients with peptic ulcer, atrophic gastritis
      or gastric carcinoma in order to examine the pathophysiological significance of
      vacuolating cytotoxin in these diseases. METHODS: H. pylori was isolated from 18
      patients (five with peptic ulcers, seven with atrophic gastritis and six with
      gastric carcinoma). Culture supernatants of H. pylori isolates, concentrated 20
      fold, were serially diluted and then analyzed for cytotoxin activity semi
      quantitatively using A431 cells as indicator cells. The relative activity of
      vacuolating cytotoxin was defined according to the maximum dilution. RESULTS:
      Cytotoxin production was observed in two out of five, six out of seven and six
      out of six isolates from peptic ulcer, atrophic gastritis and gastric carcinoma
      patients, respectively. The mean relative activity was calculated as 0.80, 2.71
      and 2.50 in CONCLUSION: These results suggest that vacuolating cytotoxin
      producing H. pylori is strongly associated with both atrophic gastritis and
      gastric carcinoma.

PMID- 7735932
TI  - Mucosal interleukin-8 and Helicobacter pylori-associated gastroduodenal disease.
AB  - OBJECTIVE: To review the role of interleukin (IL)-8 in the immunopathology of
      Helicobacter pylori-associated gastroduodenal disease. METHOD: Literature review.
      RESULTS: In H. pylori infection, IL-8 secretion by the gastric mucosa is
      increased, particularly in patients with active neutrophilic gastritis.
      Immunoreactive IL-8 is evident in the epithelium of histologically normal gastric
      mucosa but epithelial IL-8 expression is increased in H. pylori-associated
      chronic gastritis. Gastric epithelial cell lines constitutively express IL-8
      messenger (m)RNA and IL-8 message and protein secretion can be upregulated by the
      cytokines tumour necrosis factor-alpha, IL-1 alpha and IL-1 beta. H. pylori also
      directly induces epithelial IL-8 expression in a strain-specific manner.
      Cytotoxic strains expressing the CagA protein upregulate IL-8 mRNA and IL-8
      protein secretion. CONCLUSION: IL-8 is an important chemotactic and activating
      factor for neutrophils. The secretion of IL-8 by epithelial cells is probably a
      key factor in host defences at mucosal sites, permitting a rapid polymorph
      response against infectious agents. If defence mechanisms fail and chronic
      infection results, continued upregulation of IL-8 and neutrophil activation could
      lead to mucosal damage and increased free radical formation. Mucosal IL-8
      production in H. pylori infection may be an important factor in the
      immunopathogenesis of peptic ulcer disease and also be of relevance to gastric
      carcinogenesis.

PMID- 7735933
TI  - Effects of cytotoxic factors of Helicobacter pylori on superoxide generation in
      situ in the rabbit stomach.
AB  - OBJECTIVE: To evaluate the effect of certain cytotoxic products of Helicobacter
      pylori on superoxide generation in situ and on the infiltration by
      polymorphonuclear cells into the gastric mucosa. The agents studied were ammonia,
      a culture supernatant of H. pylori, and N-formyl-methionyl-leucyl-phenylalanine
      (FMLP), a chemotactic factor. METHODS: One or two of these agents were dripped
      onto rabbit gastric epithelium. The number of polymorphonuclear cells in gastric
      mucosa were counted histologically. Superoxide generation was measured by a
      chemiluminescence method, using a Cypridina luciferin analog, 2-methyl-6-phenyl
      3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one , a chemiluminescence probe that
      responds to the generation of superoxides and singlet oxygen radicals. Bovine
      erythrocyte copper zinc superoxide dismutase was dripped to confirm that the
      increase in photon counts was a direct consequence of the generation of
      superoxides. RESULTS: The greatest infiltration of polymorphonuclear cells into
      the gastric mucosa was observed with the administration of 1 mmol/l FMLP followed
      by 5.9 mmol/l ammonia, and 10 mmol/l FMLP followed by 59 mmol/l ammonia. There
      was no increase in the number of polymorphonuclear cells in the other
      experiments. Increased chemiluminescence was observed in conjunction with the
      infiltration of polymorphonuclear cells and was inhibited by superoxide
      dismutase. CONCLUSIONS: Acute gastritis and superoxide generation in situ were
      induced by ammonia after pretreatment with FMLP.

PMID- 7735934
TI  - Effect of gastric mucosal blood flow on the pathogenesis of ammonia in
      Helicobacter pylori-induced gastric mucosal injury.
AB  - PURPOSE: We investigated the effects of the gastric mucosal blood flow on the
      pathophysiology of ammonia-induced gastric mucosal damage. DESIGN: The study was
      designed to show whether the damaging effect of ammonia, a product of
      Helicobacter pylori urease, on the gastric mucosa is increased by the decrease in
      gastric mucosal blood flow in rats subjected to ischemia. RESULTS: Although
      ammonium chloride at concentrations of 15-60 mmol/l produced no significant
      macroscopical lesion in normotensive rats, it caused severe macroscopic
      hemorrhagic gastric lesions in the stomachs of rats subjected to ischemia.
      Exposure of the stomach to the combination of ischemia and ammonium chloride (60
      600 mmol/l, pH adjusted to 7-9 with sodium hydroxide) produced macroscopic
      hemorrhagic lesions. However, exposure of the mucosa to the combination of
      ischemia and sodium hydroxide (60-600 mmol/l, pH was reduced to 7-9 with
      hydrochloric acid) produced no significant lesions. CONCLUSIONS: These results
      indicate that the mucosal lesions observed in patients infected with H. pylori
      are not caused by the alkalinity of H. pylori-produced ammonia and suggest that
      concomitant infection with H. pylori in the ischemic stomach may lead to the
      development of ulceration in these patients.

PMID- 7735936
TI  - Toxic factors of Helicobacter pylori.
AB  - PURPOSE: To review the various toxic factors produced directly or indirectly by
      Helicobacter pylori and discuss their relative importance in H. pylori infection.
      RESULTS: The toxic factors produced by H. pylori can act at different levels. At
      the epithelial cell level H. pylori enzymes generate toxic molecules: ammonia
      (urease), lysolecithin (phospholipases) and acetaldehyde (alcohol dehydrogenase).
      The harmful effects of ammonia have been studied the most intensively and seem to
      be a likely mechanism of pathogenicity. A vacuolating cytotoxin is expressed in
      50-60% of the strains while the gene is present in all. Despite the fact that its
      potential toxic effect is low, the cytotoxin is associated with ulcer
      development. Another protein, CagA is a marker for the presence of the toxin. H.
      pylori can also produce a hemolysin, a platelet-activating factor and a factor
      that alters parietal cell function. At the mucus level, it does not seem that H.
      pylori enzymes degrade mucin, and the thinness of the layer could be due to
      inhibition of mucus exocytosis. CONCLUSION: H. pylori have a wide range of toxic
      factors which can act together but no one factor is considered sufficient alone
      to explain the observed lesions.

PMID- 7735935
TI  - Essential role of Helicobacter pylori urease in gastric colonization: definite
      proof using a urease-negative mutant constructed by gene replacement.
AB  - OBJECTIVE: To investigate the involvement of urease in Helicobacter pylori
      colonization in the nude mouse stomach by using a genetically defined urease
      negative mutant. METHODS AND RESULTS: Through electroporation-mediated gene
      replacement, one of the urease genes of an H. pylori strain, CYP3401, was
      disrupted by insertion of a kanamycin-resistance determinant to construct a
      stable urease-negative mutant, HPT73. Southern analysis confirmed that gene
      replacement was achieved. The two isogenic strains were introduced into the
      stomachs of nude mice, and the number of H. pylori and the histological changes
      in the stomachs were investigated 1 or 4 weeks after the challenge. Gastritis was
      present in the CPY3401-challenged stomach, from which bacteria indistinguishable
      from CPY3401 were successfully recovered. In contrast, no gastritis was found in
      the HPT73-challenged stomach, and H. pylori was not recovered from these
      stomachs. CONCLUSION: H. pylori urease is essential for colonization of the nude
      mouse stomach.

PMID- 7735937
TI  - Genetic heterogeneity of Helicobacter pylori by pulse-field gel electrophoresis
      and re-evaluation of DNA homology.
AB  - PURPOSE: The genetic heterogeneity of Helicobacter pylori isolates was re
      evaluated by using pulse-field gel electrophoresis to examine macrorestriction
      patterns and by studying DNA homology. MATERIALS AND METHODS: Twenty H. pylori
      isolates, two closely related species, H. mustelae and H. felis, and
      Campylobacter spp. were used. Notl-digested macrorestriction patterns were
      examined by pulse-field gel electrophoresis. DNA homology was examined by the S1
      nuclease method, using [3H]-labeled DNA from H. pylori NCTC11637 and two H.
      pylori isolates for reference. RESULT: Intergenus DNA homology between H. pylori
      and Campylobacters was 50-60%. Interspecies homology between H. pylori and H.
      mustelae or H. felis was around 60%. Intraspecies homology among H. pylori
      isolates was above 80%, except for a few that exhibited 70-80% homology. These
      findings indicate that all H. pylori isolates were homogeneous and belonged to
      the same species. Notl pulse-field gel electrophoresis patterns of H. pylori
      isolates differed markedly at the individual strain level. There was no specific
      relationship to any deviation from DNA homology, and the differences were
      observed within rather homogeneous members of the species. CONCLUSION: The
      polymorphism in the Notl pulse-field gel electrophoresis patterns of H. pylori
      isolates differed markedly among strains, even though these isolates displayed
      species homogeneity, with DNA homology of 70-100%.

PMID- 7735938
TI  - Gastric disease in ferrets: effects of Helicobacter mustelae, nitrosamines and
      reconstructive gastric surgery.
AB  - PURPOSE: Animal models are being used to study the mechanisms by which
      Helicobacter spp. induce gastric disease. To assess the effects of a natural
      gastric pathogen, Helicobacter mustelae, in the development of chronic gastritis,
      premalignancy and cancer, the ferret model was studied under natural and
      experimental conditions. ANIMALS AND METHODS: H. mustelae-infected ferrets were
      used to study the metabolism of nitrates/nitrites, which are dietary and
      endogenously formed substances that have been linked to gastric cancer. The
      ferret was also manipulated by performing gastric reconstructive surgery to study
      the processing of nitrite and nitrate and to assess the effect of surgery on
      gastric pathology. In addition, the ferret was tested for its suitability as an
      animal model for the induction of gastric cancer by oral dosing with N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG). The influence of these variables on gastric
      pathology and/or metabolic outcomes was examined, and the results in ferrets were
      compared to findings in humans. RESULTS AND CONCLUSIONS: The ferret appears to be
      an ideal model for studying various gastric parameters and how these factors
      influence the development of H. mustelae-associated gastric disease. Gastric
      reconstructive surgery did not effect nitrite processing or overall severity of
      gastritis in ferrets. However, a single dose of MNNG (50 mg/kg) produced an
      unprecedented 90% gastric carcinoma in H. mustelae-infected ferrets. This implies
      that chronic inflammation induced by the bacterium is a cofactor in gastric
      carcinogenesis.

PMID- 7735939
TI  - The use of a mouse model in the study of Helicobacter sp.-associated gastric
      cancer.
AB  - HYPOTHESIS: Long-term infection with Helicobacter pylori and the associated
      gastritis is now thought to cause a predisposition to gastric cancer through
      cellular changes resulting from inflammatory damage or because of direct effects
      of the bacterium. MICE AS MODELS FOR H. PYLORI-ASSOCIATED GASTRIC CANCER: Long
      term infection of conventional Swiss mice with either H. felis or H. heilmannii
      results in atrophic gastritis. Infection of specific pathogen-free Balb/c mice
      results in the development of lesions similar to H. pylori-associated low-grade B
      cell gastric lymphomas. CONCLUSION: H. pylori-infected mice appear to be
      excellent models for the study of tumours induced by this bacterium.

PMID- 7735940
TI  - Establishment of an animal model for chronic gastritis with Helicobacter pylori:
      potential model for long-term observations.
AB  - OBJECTIVES: To assess the suitability of an established experimental model for
      chronic gastritis associated with Helicobacter pylori for use in long-term
      observations. DESIGN: In a 3-year follow-up study of acute gastritis induced by
      H. pylori using an established experimental model with Japanese monkeys, we
      compared H. pylori-infected animals (n = 6) with a non-infected control group (n
      = 7). Colonization by H. pylori, gastritis scores, volume of intracellular
      periodic acid-Schiff-positive substances and the height of antral glands were
      investigated every 3 months for 3 years and compared with those of a control
      group. RESULTS: In the infected group, persistent colonization with H. pylori was
      demonstrated by culture and histological examinations. Gastritis scores were
      significantly higher than those of the control group, and the histological
      findings were quite similar to those of chronic active gastritis observed in
      humans. Simultaneously, significant decreases in the contents of periodic acid
      Schiff-positive substances and in the height of antral glands were also
      demonstrated in infected animals. CONCLUSION: In Japanese monkeys, persistent
      colonization with H. pylori caused chronic gastritis quite similar to that
      observed in humans, thus providing a suitable animal model for evaluating the
      long-term prognosis of H. pylori infection.

PMID- 7735941
TI  - Intestinal metaplasia, atrophic gastritis and stomach cancer: trends over time.
AB  - BACKGROUND: The pathogenetic association of chronic atrophic gastritis and
      intestinal metaplasia with gastric cancer implies that the trends seen in these
      disorders over time should be similar. Both should similarly decrease in
      incidence with time, and a time-related relationship should occur between the
      incidence of gastric cancer and the rate of development of atrophic gastritis in
      the stomach of Helicobacter pylori-infected subjects. AIMS AND METHODS: We
      reviewed some recent studies from Finland on the time trends seen in chronic
      gastritis, atrophic gastritis (and intestinal metaplasia) and gastric cancer over
      a period of 15 years (1977-1992). In addition, using results from earlier studies
      from Japan and Finland, we formed hypotheses on how the time-dependent evolution
      and extension of atrophic gastritis may accord with the occurrence of gastric
      cancer in the stomach. RESULTS: Our investigations showed that the incidence of
      gastric cancer and the prevalence of H. pylori-associated gastritis, atrophic
      gastritis and intestinal metaplasia have decreased similarly in outpatient series
      during the last 15 years. Correspondingly, gastric cancer, atrophic gastritis and
      intestinal metaplasia are cohort phenomena in the population, and the prevalence
      rate of atrophic gastritis is correlated with the cohort-specific incidence of
      gastric cancer; both are high in cohorts born near the beginning of the century
      but are quite low in those born in recent decades. Since antral and angular areas
      of the stomach are primary sites for gastric cancer tumours, the earlier
      investigations indicate that the time-dependent progression of gastritis in grade
      (development of atrophic gastritis and intestinal metaplasia) and extent
      (spreading of gastritis by pylorocardial extension) is well correlated with the
      rate and predisposition of gastric cancer tumours in the distal and angular
      stomach. CONCLUSIONS: We conclude that atrophic gastritis (or intestinal
      metaplasia) and gastric cancer are very much alike in time trends and in course.
      This parallelism favours suggestions that H. pylori-associated gastritis with
      atrophic and metaplastic sequelae (atrophic gastritis) contribute to the
      pathogenesis of gastric cancer.

PMID- 7735942
TI  - Relationship between Helicobacter pylori and atrophic gastritis.
AB  - OBJECTIVES: To investigate the relationship between Helicobacter pylori and
      atrophic gastritis. DESIGN AND METHODS: The extent of atrophic gastritis was
      assessed endoscopically in 97 non-ulcer patients, and their H. pylori status was
      assessed by enzyme-linked immunosorbent assay. RESULTS: The prevalence of H.
      pylori infection was greatest in the early stages of atrophic gastritis. Small
      numbers of H. pylori-negative patients were identified at different stages during
      the extension of atrophic gastritis. CONCLUSIONS: H. pylori infection precedes
      the extension of atrophic gastritis, and a minority of patients with atrophic
      gastritis may never have been infected with H. pylori.

PMID- 7735943
TI  - The effect of the immune response to Helicobacter pylori in the development of
      intestinal metaplasia.
AB  - AIM: To determine whether cytotoxic Helicobacter pylori antibodies occur in
      gastric mucosa, and whether these antibodies contribute to the development of
      intestinal metaplasia. MATERIALS AND METHODS: The number of mononuclear
      inflammatory cells, which specifically produce immunoglobulin (Ig)G and IgA
      antibodies, was investigated by using an enzyme-linked immunospot assay and the
      fraction of mononuclear inflammatory cells determined in gastric biopsy specimens
      from 34 subjects with H. pylori infection. Assays for the cytotoxicity of H.
      pylori antibodies were performed on cultured Japanese green monkey kidney (Vero)
      cells and by in vitro tests. RESULTS: The number of IgG and IgA antibody
      producing cells was positively correlated with the degree of inflammation of the
      gastric mucosa. However, the number of IgG antibody-producing cells was lower in
      subjects with intestinal metaplasia than in those without. This was not the case
      for IgA. Significant cytotoxic damage was observed in Vero cells in vitro when
      incubated in a solution containing the H. pylori IgG antibody, antigen and
      polymorphonuclear leukocytes. No cytotoxicity was seen with the IgA antibody or
      with the antigen or polymorphonuclear leukocytes alone. CONCLUSIONS: H. pylori
      infection is associated with the appearance of immunocompetent mononuclear cells
      in gastric mucosa. These cells produce H. pylori antibodies of the IgG class
      which are capable of causing cytotoxic damage in the epithelial cells, obviously
      through activation of polymorphonuclear leukocytes by antibody-antigen complexes.
      The occurrence of these cells is inversely related to intestinal metaplasia,
      suggesting that they may be involved in the processes of epithelial damage
      leading to the appearance of intestinal metaplasia.

PMID- 7735944
TI  - Helicobacter pylori infection in gastric carcinoma.
AB  - PURPOSE: This study was undertaken to compare the pathoclinical findings in
      gastric adenocarcinoma with serum IgG antibody to Helicobacter pylori. MATERIALS
      AND METHODS: We examined 185 patients with histologically established gastric
      cancer. The presence of immunoglobulin (Ig)G antibody in the high molecular cell
      associated antigen of H. pylori was determined by enzyme-linked immunosorbent
      assay. Pepsinogens I and II were measured by radioimmunoassay. The distribution
      of H. pylori on the gastric mucosa was assessed by the Campylobacter-like
      organism test and phenol red dye spraying. RESULTS: H. pylori IgG antibody was
      detected in 93.1% of patients with gastric cancer (mean age 61.7 years), 94.3% of
      patients with early gastric cancer and 91.2% with advanced gastric cancer. No
      statistical difference in serology was observed between type of gastric cancer,
      depth of cancer invasion, tumor size or histology. Only in patients with diffuse
      type cancer of the cardia was there a lower percentage of positive results
      (80.0%). The ratio of pepsinogen I to pepsinogen II was higher in the patients
      who exhibited no H. pylori antibodies. CONCLUSIONS: H. pylori antibodies were
      common in patients with gastric cancer, and were not correlated with histological
      type nor stage of cancer. In the Niigata district, a higher percentage of
      patients with gastric carcinoma displayed H. pylori antibodies compared with
      other districts in Japan.

PMID- 7735945
TI  - Gene alterations in intestinal metaplasia and gastric cancer.
AB  - PURPOSE: To review genetic alterations in precancerous lesions and adenocarcinoma
      of the stomach. RESULTS: Telomere reduction, tpr-met oncogenic rearrangement,
      overexpression of cripto, p53 mutations, adenomatous polyposis coli gene
      mutations and K-ras mutations, which are frequently associated with the well
      differentiated or intestinal type of stomach cancer, were found in intestinal
      metaplasia and adenoma of the stomach. CONCLUSIONS: Among these genetic
      alterations, reduction of telomere repeat arrays might be the initial step in the
      genetic instability of stomach carcinogenesis. Some of the well differentiated
      type stomach cancers may develop by an accumulation of multiple gene changes
      similar to those of colorectal cancer.

PMID- 7735946
TI  - The sequence of injury determines the degree of lung damage in both inhalation
      and thermal injuries.
AB  - The lung damage resulting from smoke inhalation is an important determinant of
      morbidity and mortality in thermally injured patients. We hypothesized that the
      degree of pulmonary microvascular damage seen with smoke inhalation could be
      affected by whether the smoke insult preceded or followed thermal injury. Fifteen
      chronically instrumented sheep were divided into two groups: seven were given a
      40% 3rd-degree flame burn and then insufflated with smoke (smoke after burn
      group); eight were insufflated with smoke and then given thermal injury (smoke
      before burn group). Lung lymph flow and wet/dry weight ratio were significantly
      higher in smoke before burn group animals. We conclude that lung damage is
      minimized when thermal injury precedes smoke inhalation injury.

PMID- 7735947
TI  - Hypertonic saline improves cerebral oxidative metabolism and cytochrome aa3 redox
      state during hemorrhagic hypotension in dogs.
AB  - Hypertonic saline used in the treatment of hemorrhagic shock dramatically
      improves cardiovascular performance. In the present study, our focus was on
      whether it would improve disturbances of cerebral oxidative metabolism induced by
      hemorrhagic hypotension. Fourteen dogs were bled over a period of 15 min so that
      the mean arterial blood pressure of seven dogs (group H) fell to 65 mmHg and that
      of the other seven (group L), to 45 mmHg. These pressures were maintained for 30
      min, and then 20% hypertonic saline (1.5 ml/kg body weight) was injected
      intravenously. Cerebral oxyhemoglobin, deoxyhemoglobin, cerebral blood volume,
      and oxidized cytochrome aa3 were continuously monitored by near-infrared
      spectroscopy throughout the experiment. The experimental results showed that 45
      min of hemorrhagic hypotension led to decreases in cerebral oxyhemoglobin (from
      control level 0 to -25.5 +/- 7.5 microM/liter brain tissue in group H and to 
      32.3 +/- 7.5 microM/liter brain tissue in group L), in total hemoglobin (from
      control level 0 to -7.2 +/- 1.8 microM/liter brain tissue in group H and to -6.5
      +/- 1.7 microM/liter brain tissue in group L), and in oxidized cytochrome aa3 in
      group L (from control level 0 to -0.8 +/- 0.4 microM/liter brain tissue), but to
      increases in deoxyhemoglobin (from control level 0 to 15.5 +/- 5.0 microM/liter
      brain tissue in group H and to 25.8 +/- 3.4 microM/liter brain tissue in group L)
      and in oxidized cytochrome aa3 in group H (from control level 0 to 0.6 +/- 0.3
      microM/liter brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735948
TI  - Plasma tumor necrosis factor and post-traumatic hyperdynamic sepsis evoked by
      endotoxin.
AB  - To examine the role of systemic plasma tumor necrosis factor (TNF) in the septic
      response following trauma, an endotoxin (lipopolysaccharide (LPS)) challenge was
      administered to anesthetized mongrel pigs 72 h following either hemorrhagic
      shock/resuscitation or sham shock. For TNF to be considered a mediator, at least
      two conditions should be satisfied: a TNF increase should precede other
      manifestations of the septic response and the magnitude of that increase should
      correlate with the symptoms. Immediately following resuscitation from shock,
      hemodynamics were stable, but heart rate, cardiac index (CI), and systemic oxygen
      delivery (DO2) were elevated 20-60%, and systemic vascular resistance (SVR) was
      decreased 40%, relative to the preshock baseline. After 72 h, the animals were
      reanesthetized, reinstrumented, and all hemodynamic values were near normal in
      both groups. At this point, either 1.5 (shock, n = 2; sham, n = 2), 15 (shock, n
      = 7; sham, n = 6) or 150 (shock, n = 11; sham, n = 4) micrograms/kg of
      Escherichia coli LPS was administered intravenously over 30 min. Serial
      hemodynamic data, complete blood counts, and TNF were recorded for 3 h post-LPS.
      LPS evoked profound leukopenia and pulmonary hypertension within 15 min that was
      followed by a hyperdynamic septic response (i.e., progressive arterial
      desaturation, tachypnea, tachycardia, increased CI, and decreased SVR) and rise
      in plasma TNF at 60-90 min. In the shock group, LPS-evoked TNF changes were less
      than or equal to those in the sham group, even though mortality was higher after
      shock.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735949
TI  - Endothelin-stimulated monocyte supernatants enhance neutrophil superoxide
      production.
AB  - Endothelin-1 (ET-1) is a vasoconstrictive peptide released by ischemic/injured
      endothelium which increases intracellular ionized calcium [Ca2+]i in vascular
      smooth muscle. Previous work from this lab has shown that ET-1 also increases
      human peripheral blood monocyte [Ca2+]i, and that 24 h incubation of monocytes
      with 10(-9) M ET-1 causes production of prostaglandin E2 and interleukin-6. In
      these studies, ET-1-stimulated monocyte supernatants were evaluated for their
      effect on neutrophil superoxide production. While ET-1 alone had no direct
      effect, incubation of neutrophils for 20 min in ET-1-stimulated monocyte
      supernatants resulted in a 10-fold increase in superoxide production over basal
      levels, 44% as much superoxide production as induced by peptide N-formyl
      methionyl-leucyl-phenylalanine (N = 6, p < .001). Monocyte supernatants were
      analyzed for interleukin-8 (IL-8 or neutrophil activation protein) content by
      radioimmunoassay. ET-1-stimulation resulted in production of 54% as much IL-8 as
      lipopolysaccharide controls (N = 6, p < .001). While a number of monokines can
      activate neutrophils, IL-8 has been shown to be a potent neutrophil activator as
      well as a superoxide primer. Therefore, ET-1-treated monocytes probably
      upregulate neutrophil superoxide production via a mechanism which includes IL-8.

PMID- 7735950
TI  - A quantitative analysis of transcapillary refill in severe hemorrhagic
      hypotension in dogs.
AB  - In pressure-driven hemorrhage (PDH), where the rate of bleeding is a function of
      prevailing arterial pressure, survival time, arterial pressure, cardiac output,
      oxygen consumption, and base excess are functions of initial bleeding rate. The
      quantitative rate of transcapillary refill (TR) throughout PDH leading to death
      was determined in splenectomized dogs, through serial analysis of Cr51-tagged red
      cell dilution. Mild, moderate, and severe levels of PDH were produced by varying
      initial bleeding rate (10, 25, and 50 ml/min, respectively). The rate of TR is a
      function of the severity of PDH, but does not correlate with arterial pressure,
      cardiac output, or systemic resistance. The volume of transferred fluid
      represents an ever increasing fraction of total plasma volume, and accounts for
      more than 75% of plasma volume in preterminal stages of shock. TR sustains a
      relatively fixed level of plasma volume, equivalent to two-third of the initial
      plasma volume, irrespective of the rate of bleeding. Hypertonic NaCl (7.5%)
      enhances TR, while isotonic NaCl reverses it.

PMID- 7735951
TI  - Effects of sodium bicarbonate on striated muscle metabolism and intracellular pH
      during endotoxic shock.
AB  - The effects of HCO3Na load on acid-base balance and muscle intracellular
      bioenergetics have been investigated using 31P-magnetic resonance spectroscopy in
      an experimental model of endotoxinic shock. Anesthetized, mechanically
      ventilated, and paralyzed rats (n = 16) were given an intravenous bolus of
      Escherichia coli lipopolysaccharide (15 mg/kg). When shock was established they
      were randomly assigned to receive either HCO3Na intravenously (2 mmol/kg in 2
      min) or an equimolar saline injection. Lipopolysaccharide induced a significant
      decrease in the levels of mean arterial pressure (58 +/- 6 vs. 120 +/- 8 mmHg),
      arterial pH (7.20 +/- .03 vs. 7.35 +/- .01), intracellular pH (6.86 +/- .04 vs.
      7.08 +/- .01), a marked hyperlactatemia (7 +/- 3 vs. 1.2 +/- .2 mmol/L) and a
      drop in the phosphocreatine-inorganic phosphate ratio. In the bicarbonate-loaded
      rats, mean arterial pressure further decreased whereas it remained unchanged in
      the saline group. Bicarbonate increased arterial pH and PaCO2 transiently. In the
      saline group, arterial pH decreased and PaCO2 remained stable. In both groups,
      intracellular pH and high energy phosphates had a similar evolution. In this
      model of septic shock, partial correction of arterial pH using HCO3Na did not
      reduce the metabolic cellular injury in skeletal muscle. Based on these results,
      HCO3Na may be of limited therapeutic value in severe septic metabolic acidosis.

PMID- 7735952
TI  - Porcine peritoneal sepsis: modeling for clinical relevance.
AB  - The characteristics of two types of intraperitoneal (i.p.) soilage sepsis models,
      autologous fecal inoculum (FEC) and a pure culture of Escherichia coli (EC), were
      studied in 26 male Yucatan minipigs (20-30 kg). Early (1-4 h) and late (24-72 h)
      changes were different between the two groups. The EC group was characterized
      early by hypotension, low cardiac output, and increased systemic and pulmonary
      vascular resistances, along with leukopenia, hypoglycemia, lactacidemia, and
      elevated blood urea nitrogen. Of the pigs in the EC group that survived the early
      effects, there were few significant differences in physiological parameters,
      compared to control pigs, that would indicate ongoing pathological processes. In
      contrast, the FEC group pigs demonstrated early hypotension, but with increased
      cardiac output and reduced systemic vascular resistance. Other parameter changes
      were similar to those seen in the EC pigs, but to a lesser degree, with the
      exception of elevations in serum lactate dehydrogenase. Also in contrast to the
      EC group, most of the changes in the FEC group persisted in later days, and FEC
      pigs demonstrated leukocytosis. There were also greater elevations in circulating
      lipopolysaccharide (LPS) concentrations in the EC group that returned later to
      baseline levels. In the FEC group, there were persistently elevated LPS
      concentrations over 72 h. These observations suggest that pigs challenged with
      intraperitoneal E. coli demonstrated an initial acute peritonitis and damaging
      physiologic effects of high levels of circulating LPS. Survivors in this group
      improved and were physiologically stable after 24 h. Pigs that received i.p.
      autologous feces developed an early acute peritonitis phase with lower levels of
      circulating LPS, and later developed pronounced peritoneal reaction as
      demonstrated by multiple abdominal abscesses, pyogenic granuloma formation, and
      adhesions with physiological evidence of developing sepsis over 72 h. These
      observations indicate that i.p. EC models evoke a systemic response not unlike
      intravenous administration of LPS or EC, however, the FEC model produced a
      systemic response akin to a slower developing septic process.

PMID- 7735953
TI  - Fluorescent monitoring of Jurkatt cell intracellular magnesium during metabolic
      poisoning.
AB  - Divalent cation movement characterizes the final common pathway of cellular death
      from ischemic or metabolic injury. The influx of calcium is an essential step in
      cellular death. We hypothesized that intracellular magnesium levels may change
      during the progression to cellular death. Verapamil-sensitive changes in free
      ionized intracellular Mg2+ ([Mg2+[i) and Ca2+ ([Ca2+]i) levels were estimated in
      transformed T-lymphocytes exposed to metabolic inhibitors. Separate experiments
      used a Mg(2+)-sensitive fluoroprobe, fura-2 (Ex 1,344, Ex 2,376, Em 500), and a
      Ca(2+)-sensitive fluoroprobe, fura-2 (Ex 1,340, Ex 2,380, Em 510). Chemical
      anoxia (sodium cyanide 1 mM, iodoacetic acid 10 mM) caused a gradual increase in
      [Ca2+]i (control 126 +/- 13 nM) to > 1 mM by 10 min. This increase in [Ca2+]i was
      not affected by verapamil treatment. In separate experiments, [Mg2+]i levels were
      monitored during chemical anoxia. The specificity of mag-fura for Mg2+ over Ca2+
      was reflected in the absence of a response to the lymphocyte Ca2+ mobilizer OKT
      3. Uncorrected control [Mg2+]i levels (.4 +/- .1 mM) were not affected by the
      combined cyanide-iodoacetate treatment. A small increase in mag-fura-2
      fluorescence was noted, probably due to binding of Ca2+ to the fluoroprobe when
      [Ca2]i exceeded 1 mM. Elimination of Ca2+ from the extracellular buffer increased
      the resting estimate of intracellular [Mg2+] to 1.6 + .1 mM. These results
      indicate that 1) extracellular Ca2+ can interfere with the fluorescent
      determination of intracellular magnesium concentration, and 2) intracellular free
      Mg2+ concentrations do not change in this cell line during chemical anoxia.

PMID- 7735954
TI  - The catabolism of apolipoprotein B from very low density lipoprotein and
      triglyceride-rich lipoprotein remnants in fasted septic rats.
AB  - The catabolism of apolipoprotein B (apo B) from very low density lipoproteins
      (VLDL) and triglyceride-rich lipoprotein (TRL) remnants in fasted control (C) and
      Escherichia coli-treated septic (S) rats was measured. In Experiment 1,
      [125I]VLDL was injected into rats from C and S groups. Blood was collected from 0
      to 60 min postdose and apo B was isolated and counted for radioactivity. No
      significant difference in the half-life (t1/2) or fractional catabolic rate (FCR)
      of apo B was observed in the VLDL fraction. In Experiment 2, [125I]TRL remnants
      were injected into rats from C and S groups. Blood was collected from 0 to 90 min
      postdose and apo B isolated. The t1/2 was 2.5 times longer in the S compared with
      the C and the FCR was slower in the S rats. These experiments suggest that S rats
      do not clear triglyceride-rich lipoproteins as easily as normal-sized
      lipoproteins.

PMID- 7735955
TI  - Deferoxamine induces hypotension in experimental gram-negative septicemia.
AB  - Multiple organ system failure may result from tissue damage caused by activated
      neutrophils or endotoxin. A significant part of this tissue damage is due to
      peroxidation induced by oxygen-free radicals and requires iron as a co-factor.
      Iron chelation has been shown to prevent tissue damage in some models. This
      experiment was carried out to determine whether iron chelation with deferoxamine
      (DFO) would prevent lung damage in a swine model of Gram-negative septicemia.
      Fifteen animals were randomized to control, Pseudomonas aeruginosa infusion at a
      rate of 2 x 10(7) colony forming units/20 kg/min (septic group), or Pseudomonas
      infusion combined with DFO pretreatment at a dose of 80 mg/kg/h (septic-treated
      group). Three of six septic-treated animals became severely hypotensive and died
      during the course of the experiment as opposed to none of six septic animals.
      Surviving septic-treated animals were significantly hypotensive (60 +/- 24 mmHg
      mean arterial pressure) compared to septic (122 +/- 9 mmHg) and control (109 +/-
      8 mmHg) animals. DFO did not improve respiratory function (e.g., pO2) or
      morphology in septic animals. We conclude that iron-chelation therapy with DFO at
      the above dosage results in a significant deterioration in cardiovascular
      function in septic swine. Lung damage was not prevented.

PMID- 7735956
TI  - Hemorrhage induces a reduction in the capacity of macrophages to mobilize
      intracellular calcium secondary to formyl-methionyl-leucyl-phenylalanine
      stimulation: association with alterations in cells surface Fc receptor expression
      and increased prostaglandin release.
AB  - Studies indicate that simple hemorrhage induces profound suppression in splenic
      and peritoneal macrophage (Mphi) functions such as antigen presentation, reduced
      major histocompatibility complex class II antigen expression, as well as cytokine
      release. Since many of these macrophage functions require the mobilization of
      [Ca2+]i, our aim was to determine whether or not hemorrhage produced changes in
      the splenic and/or peritoneal Mphi's ability to mobilize [Ca2+]i. Mphis taken
      from mice (C3H/HeN) 2 h posthemorrhage (1 h duration; 35 mm Hg), exhibited a
      significantly reduced capacity to mobilize [Ca2+]i when exposed to formyl
      methionyl-leucyl-phenylalanine (FMLP) compared to shams. This loss of the
      capacity to mobilize [Ca2+]i in response to FMLP stimulation was not due to an
      inability of Mphis to recruit Ca2+ from extracellular sources. Staurosporine
      pretreatment ablated the response to FMLP and, since these cells produced less
      inositol 1,4,5-triphosphate, this indicates that Mphis taken from hemorrhage
      animals are unable to recruit Ca2+ from intracellular stores. This dysfunction,
      which was observed following hemorrhage, was associated with the decrease in the
      number of Fc receptor-positive cells. However, despite this loss, the residual Fc
      receptor-positive cells present following hemorrhage were capable of releasing
      enhanced levels of PGE2. It may well be that the residual Fc receptor population
      represents a sub-population of cells which have been differentially primed for
      enhanced PGE2 release by the hypotensive insult.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735958
TI  - Changes in skeletal muscle pO2 after administration of anti-TNF alpha-antibody in
      patients with severe sepsis: comparison to interleukin-6 serum levels, APACHE II,
      and Elebute scores.
AB  - In 20 patients with severe sepsis, skeletal muscle pO2 was continuously measured
      in order to assess whether a decrease of skeletal muscle pO2 was accompanied by
      an improvement of sepsis after repeated administration of F(ab')2 fragments of a
      murine anti-TNF alpha-antibody. Abnormally high skeletal muscle pO2 decreased
      from 43.5 +/- 10.9 mmHg (day 0) to 36.4 +/- 10.1 mmHg within 24 h after the first
      administration of anti-TNF alpha-antibody (day 1, p = .006, n = 20) and remained
      at 34.6 +/- 7.7 mmHg thereafter (mean day 2-7, p = .004). The decrease of
      skeletal muscle pO2 within 24 h exceeded 5 mmHg (-7 to -19 mmHg) in 11 patients
      in contrast to nine patients (-4 to +4 mmHg). Only in the patients showing a
      decrease of skeletal muscle pO2 did sepsis improve as determined by Elebute
      score, APACHE II score, and interleukin-6 serum levels. The change of skeletal
      muscle pO2 within 24 h was associated with a change of interleukin-6 serum levels
      within 24 h (r = .5, n = 20), with a change of Elebute score (r = .7, n = 20) and
      of APACHE II score (r = .62). These data suggest that a decrease of skeletal
      muscle pO2 might be an early indicator of improvement of sepsis after
      administration of anti-TNF alpha-antibodies.

PMID- 7735957
TI  - Repeated administration of a F(ab')2 fragment of an anti-tumor necrosis factor
      alpha monoclonal antibody in patients with severe sepsis: effects on the
      cardiovascular system and cytokine levels.
AB  - In an uncontrolled clinical trial the effects of repeated administration of the
      F(ab')2 fragment of a murine monoclonal anti-tumor necrosis factor alpha (TNF
      alpha)-antibody (MAK 195F) on cytokine levels and the cardiovascular system were
      studied in 20 patients with severe sepsis. Patients were treated with a total of
      11 single dosages of the anti-TNF alpha-antibody intravenously over 5 days using
      either 1 mg/kg (n = 10) or 3 mg/kg (n = 10). The anti-TNF alpha-antibody was well
      tolerated in all patients without signs of toxicity and without development of
      anti-murine antibodies. As assessed by cytokine levels (TNF alpha, Interleukin-6)
      and hemodynamics there was no evidence that the higher dosage of the anti-TNF
      alpha-antibody (3 mg/kg per dose) was more effective than the lower dosage (1
      mg/kg per dose). Comparison of our data with recent data from phase I or II
      trials using a complete murine monoclonal anti-TNF alpha-antibody suggest that
      the F(ab')2 fragments of the murine monoclonal anti-TNF alpha-antibody may be of
      similar efficacy. Definitive conclusions, however, with respect to improvement of
      mortality and improvement of the cardiovascular system, await the results of
      larger ongoing placebo-controlled trials.

PMID- 7735959
TI  - CT-1501R selectively inhibits induced inflammatory monokines in human whole blood
      ex vivo.
AB  - The effect of (R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine (CT-1501R; the
      nonproprietary name for CT-1501R approved by the United States Name Council is
      lisofylline), an inhibitor of second messenger signaling through phosphatidic
      acid, on release of endogenous mediators important in the systemic inflammatory
      response syndrome (SIRS) was studied using the human whole blood ex vivo assay
      system. Human blood was stimulated with various endotoxin preparations, zymosan,
      or protein A, and the levels of secreted monokines were measured by enzyme-linked
      immunosorbent assay. CT-1501R inhibited tumor necrosis factor alpha (TNF-alpha),
      interleukin 1 beta (IL-1 beta), and IL-6 release in a dose-dependent manner and
      was active with all stimuli tested including Salmonella and Escherichia coli
      derived endotoxin, endotoxin from both rough and smooth E. coli strains, as well
      as zymosan and protein A. CT-1501R inhibited monokine release by approximately
      50% at 200 microM and 30% at 50 microM and was independent of the relative
      potency of stimulus. CT-1501R also inhibited IL-1 alpha or IL-1 beta induction of
      either TNF-alpha or IL-1 beta and inhibited the synergistic effects of
      stimulation with both human IL-1 beta and murine TNF-alpha on release of human
      TNF-alpha. Inhibition of monokine release following stimulation with monokine(s)
      was, in general, greater than that achieved with lipopolysaccharide (LPS)
      stimulation. Northern blot analysis showed decreased mRNA accumulation of TNF
      alpha and IL-1 beta in CT-1501R-treated samples following LPS stimulation
      suggesting that CT-1501R acts at least in part, at the pretranslational level. In
      contrast, CT-1501R does not inhibit LPS-stimulated IL-8 or IL-1 receptor
      antagonist (IL-1ra) release in human whole blood or IL-1 alpha-induced release of
      PGE2 in human foreskin fibroblast cells. These data suggest that CT-1501R may be
      of use for clinical intervention in SIRS.

PMID- 7735960
TI  - T-lymphocyte Ca2+ signalling and proliferative responses during sepsis.
AB  - Alterations in T-lymphocyte kinetics and/or activation have been implicated in
      burn and traumatic injury. This study evaluated concanavalin A (Con A) regulation
      of both intracellular Ca2+ (Cai2+) and proliferation in T-lymphocytes harvested
      from spleens of septic rats. Rats were implanted with fecal pellets containing
      Escherichia coli (150 colony forming units (CFU)) and Bacteroides fragilis (10(4)
      CFU). T-cell[Ca2+]i was measured before and after treatment of cells with ConA,
      using Fura-2 and microfluorophotometry. Splenic lymphocytes were cultured for 72
      h with Con A to assess their proliferative response. As compared to sterile
      implanted rats, the septic rat T-lymphocytes Cai2+ response to Con A
      significantly decreased on days 1 and 2 after implantation. A significant
      decrease in T-cell proliferative response to Con A, compared to sterile controls,
      was found in septic rats on day 2 but not on day 1. These results suggest that
      Con A-mediated proliferation in T-cells occurs secondarily to a decrease in
      cellular Ca2+ signalling. The depression in the T-cell proliferative response
      during sepsis could contribute to a decrease in host's resistance against sepsis.

PMID- 7735961
TI  - Effect of activation on neutrophil-induced hepatic microvascular injury in
      isolated rat liver.
AB  - Polymorphonuclear neutrophils (PMNs) have been implicated in microvascular injury
      following ischemia and reperfusion (I/R) but the relative contribution of
      obstruction versus toxic mediators is not well defined. Therefore, the present
      study was performed to determine the contribution of exogenous or endogenous
      activation on PMN-induced microvascular and hepatocyte injury. Rat livers were
      isolated and perfused at constant pressure with Krebs buffer with red cells (Hct
      10%) and monitored for perfused sinusoids (PS) and dead hepatocytes (propidium
      iodide-stained, DH) by intravital microscopy. PMNs isolated from the peritoneum
      after oyster glycogen injection were added to the perfusate either without or
      with activation by phorbol myristate acetate (PMA, 160 nM). Unactivated PMNs
      stuck in the liver but had no significant effect on either perfused sinusoids
      (11.1 +/- .4/field, unactivated PMNs versus 11.9 +/- .5/field, the time-matched
      control) or dead hepatocytes (1.2 +/- .4/field, unactivated PMNs versus 1 +/-
      .3/field, the time-matched control). Infusion of PMA-activated PMNs resulted in
      significant decrease in perfused sinusoids and increase in DH (9.5 +/- .3/field
      for PS and 3.2 +/- .6/field for DH, respectively). In contrast, when PMNs were
      "activated" by infusion into a liver previously made ischemic for 30 min, DH were
      significantly increased after 60 min (26.2 +/- 4.5/field, I/R plus PMNs versus
      12.4 +/- 2/field, I/R only) but perfused sinusoids were not different from
      ischemia alone. These results demonstrate that oxidatively quiescent PMNs do not
      cause cellular or microvascular injury in spite of microvascular accumulation.
      Activated PMNs damage microcirculation or hepatocytes depending on the nature of
      the activation.

PMID- 7735962
TI  - Escherichia coli endotoxemia alters coronary and pulmonary arteriolar responses
      to platelet products.
AB  - In order to examine the effects of Escherichia coli endotoxemia on coronary and
      pulmonary microvascular responses to serotonin (5-HT) and ADP, arterioles (80-190
      micros diameter) were isolated from pigs 3 h after administration of E. coli
      endotoxin (150 micrograms/kg, intravenously over 1 h, n = 8) or Ringer's lactate
      (control, n = 8). Arterioles were studied in vitro in a pressurized, partially
      contracted, no-flow state with video-microscopy. Precontracted (30-50% of
      baseline diameter) control coronary arterioles dilated in responses to either 5
      HT (24 +/- 2%) or ADP (89 +/- 2%). These relaxations were partially inhibited by
      indomethacin, but were markedly reduced with nitric oxide synthase inhibition.
      After 3 h of endotoxemia, 5-HT caused contraction of coronary arterioles which
      was inhibited with indomethacin. In the presence of indomethacin, coronary
      vessels from endotoxic pigs relaxed slightly, but significantly, more to 5-HT
      than did control vessels exposed to indomethacin. In contrast, the relaxation
      response to ADP was unchanged following endotoxemia. Precontracted (15-30% of
      baseline diameter) pulmonary arterioles dilated in response to 5-HT (13 +/- 1%)
      or ADP (67 +/- 3%). Following 3 h of endotoxemia, the pulmonary arteriolar
      relaxation induced by 5-HT was reduced, whereas the response to ADP was not
      altered. In both coronary and pulmonary arterioles, relaxation induced by the
      endothelium-independent vasodilator, sodium nitroprusside, was unaffected by
      endotoxemia. Thus, coronary and pulmonary microvascular relaxation response to
      ADP are minimally affected by 3 h of endotoxemia, but relaxation responses to 5
      HT are significantly reduced or converted to contractile responses.

PMID- 7735963
TI  - Bacterial translocation after burn injury: the contribution of ischemia and
      permeability changes.
AB  - Bacterial translocation (BT) has been shown to occur in stress and trauma. In
      this study, we examined the contribution of altered intestinal permeability
      (measured with 51Cr-EDTA) and intestinal blood flow (radioactive microspheres) to
      the loss of intestinal barrier function after burn injury. A 42.6 +/- 0.6% total
      body surface area scald burn was produced in Sprague-Dawley rats; sham burn
      animals served as controls. Rats (29 burn and 20 sham burn) were sacrificed 24 h
      postburn, and mesenteric nodes (MLN), cecum, spleen, and liver were cultured. The
      incidence of BT was significantly higher in burn compared to shams (MLN, 55 vs.
      15%; spleen, 31 vs. 10%; liver, 31 vs. 10%; p < .05). Cecal concentration of Gram
      negative bacteria were similar in all rats (5.2 +/- 0.2 x 10(8) colony forming
      units/g). 5 h postburn, intestinal blood flow decreased significantly in burn
      (1.60 +/- .20) compared to shams (2.49 +/- .24 ml/min/g, p = .01); at this time,
      plasma to luminal clearance of 51Cr-EDTA was greater in the burn (.146 +/- .033,
      N = 9) than in shams (.050 +/- .010 ml/min/100 g, N = 9, p = .001); 24 h
      postburn, there was no significant difference in intestinal blood flow in sham
      (2.86 +/- .46, N = 10) and burn rats (2.29 +/- .44 ml/min/g, N = 11); plasma to
      intestinal lumen clearance of 51Cr-EDTA was similar in sham (.054 +/- .010, N =
      11) and burn rats (.051 +/- .006 ml/min/100 g, N = 12) 24 h postburn.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7735964
TI  - Left ventricular dysfunction and acute lung injury induced by continuous
      administration of endotoxin in sheep.
AB  - Sixteen sheep were surgically prepared for chronic study. Seven days later,
      Escherichia coli endotoxin (10 ng/kg/min, lipopolysaccharide (LPS) group, n = 10)
      or an equivalent amount of 0.9% NaCl (Control group n = 6) was administered.
      Between 1 and 8 h post-LPS, there was a hypodynamic state with low cardiac index
      (CI, LPS 5.0 +/- 0.2; sham 6.3 +/- 0.4 liters/min/m2 at 4 h). During this period,
      the left ventricular end-systolic pressure-diameter relationship (ESPDR), a
      sensitive index of myocardial contractility, was also lower (LPS 10.4 +/- 1.2;
      sham 17.2 +/- 0.8 mmHg/mm). Mean pulmonary arterial pressure (PAP) and pulmonary
      vascular resistance index (PVRI) were remarkably increased 1 h after the
      administration of LPS (PAP:LPS 37.5 +/- 1.9; sham 21.8 +/- 0.9 mmHg, PVRI: LPS
      600 +/- 58; sham 158 +/- 23 dynes x s x cm-5 x m2). The early changes in
      cardiopulmonary function occurred concomitantly with an elevation in tumor
      necrosis factor (LPS 1221 +/- 520; sham 0 +/- 0 pg/ml) and thromboxane B2 (LPS
      1382 +/- 266; baseline 82 +/- 20 pg/ml) in arterial blood. Following this first
      phase, the sheep presented a persistent hyperdynamic state characterized by a
      significant increase in CI. The ESPDR continued to fall. By 24 h post-LPS the CI
      was 10.1 +/- 0.5 liters/min/m2 (sham, 6.3 +/- 0.3) but the ESPDR had fallen to
      8.2 +/- 2.3 mmHg/mm (sham 16.0 +/- 3.0). The pulmonary hypertension was
      maintained for the duration of the LPS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735965
TI  - Comparison of plasma reduced glutathione and oxidized glutathione with lung and
      liver tissue oxidant and antioxidant activity during acute inflammation.
AB  - We determined whether plasma levels of reduced glutathione (GSH) and oxidized
      glutathione (GSSG) accurately reflect the tissue GSH and GSSG levels in lung and
      liver during a progressive acute inflammation-induced increased oxidant activity.
      We also determined whether plasma GSH also reflected other antioxidant defenses.
      Male Wistar rats (n = 38) were given intraperitoneal zymosan (.75 mg/g body
      weight) producing an acute progressive peritonitis and generalized inflammation.
      Animals were resuscitated then killed at 4 or 24 h. Plasma and tissue levels of
      GSH, GSSG, vitamin C, alpha-tocopherol, and catalase were measured. Conjugated
      dienes and malondialdehyde were used as tissue markers of lipid peroxidation. We
      found lung and liver tissue GSH to be decreased significantly at 4 h while GSSG
      was increased. Lipid peroxidation was also present in the lung. At 24 h, GSH
      remained decreased in liver and GSSG remained increased in lung along with the
      lipid peroxides conjugated dienes and malondialdehyde. In addition, overall
      antioxidant defenses were decreased in both lung and liver. Plasma GSH remained
      decreased at 24 h corresponding with the decrease in liver GSH as well as the
      decrease in other plasma and tissue antioxidants. However, plasma GSSG levels
      were not significantly increased, at any time point, indicating plasma GSSG does
      not accurately reflect tissue oxidant activity.

PMID- 7735966
TI  - Evaluating oxidant or antioxidant status.

PMID- 7735967
TI  - Alterations of glucose transporter mRNA and protein levels in brain following
      thermal injury and sepsis in mice.
AB  - Since glucose transport and utilization are profoundly influenced by injury and
      infection, and the brain is an organ which primarily utilizes glucose as its
      energy source, we examined the status of the facilitative glucose transporters
      GLUT1 and GLUT3 in brain following thermal injury and infection. BDF1 mice
      underwent a 15% total body surface area burn with or without Pseudomonas
      aeruginosa infection. At 4 and 72 h post injury +/- infection, GLUT1 and GLUT3
      mRNA abundance was measured by Northern blotting, and the correlative proteins
      determined using Western blotting. At 4 h, both brain GLUT1 mRNA and protein
      abundance were significantly increased in burned (mRNA 150 +/- 12%, protein 122
      +/- 6%) and burn/infected (mRNA 165 +/- 11%, protein 119 +/- 5%) animals. At 72
      h, GLUT1 mRNA and protein levels were also significantly increased in burn (mRNA:
      139 +/- 11%, protein: 120 +/- 7%) and burn/infected (mRNA: 145 +/- 14%, protein:
      138 +/- 8%) animals. Our studies suggest that alterations of GLUT1 mRNA and
      protein abundance were primary responses to the burn injury and were not further
      altered by burn wound infection.

PMID- 7735968
TI  - Staurosporine encapsulated into pH-sensitive liposomes reduces tnf production and
      increases survival in rat endotoxin shock.
AB  - Bacterial lipopolysaccharide (LPS) can elicit septic shock; however, there is
      growing evidence that most of its pathophysiological effects are mediated by the
      release of tumor necrosis factor (TNF) and other cytokines. In turn, LPS-induced
      TNF production is thought to implicate the activation of intracellular protein
      kinase C (PKC). In this study, we examined whether pH-sensitive liposomes
      containing staurosporine (STP), a potent inhibitor of PKC, when injected
      intravenously would suppress TNF production and reduce mortality in an endotoxin
      rat model. We found that pretreatment of rats with pH-sensitive STP-liposomes by
      intravenous administration 1.5 h prior to LPS injection decreased lethality from
      80% to approximately 30%. Importantly, this improvement in outcome was associated
      with significant reductions in TNF serum levels; 1 h after LPS injection serum
      TNF was 73% lower than in a saline control group, and at 2 h TNF levels were 84%
      lower. STP-liposome pretreatment also ameliorated the severe reduction in body
      temperature, characteristic for a hypodynamic shock, that was observed in LPS
      challenged rats, but had relatively little effect on the transient leukopenia. We
      conclude that STP-liposomes can suppress LPS-induced TNF production by the
      mononuclear phagocytic system, can reduce the symptoms of septic shock, and can
      increase survival.

PMID- 7735969
TI  - The effects of hypovolemia on multiple organ injury following intestinal
      reperfusion.
AB  - This study examines the relationship between hypovolemia and remote organ injury
      following intestinal reperfusion. Sprague-Dawley rats underwent intestinal
      ischemia (120 min) and reperfusion (90 min, IIR) or sham operation (CTL). The
      animals received normal saline (NS) at 0, 30, or 40 ml/kg/h intravenously. Lung
      and intestinal injury was quantitated using an edema index, and liver injury was
      assessed by measuring bile flow rates. The infusion of 40 ml/kg/h of NS
      attenuated the intestinal edema index of IIR animals nearly 50% (p < .05).
      Despite this improvement, this parameter remained nearly 10-fold greater than
      that of CTL (p < .05). The lung edema index was 70% greater in IIR animals
      receiving 30 and 40 ml/kg/h of NS than those not receiving NS. The infusion of 40
      ml/kg/h of NS restored bile flow rates in IIR animals to that of CTL. These data
      suggest that hypovolemia may contribute to the intestinal and hepatic injury in
      this model. The lung injury is independent of hypovolemia.

PMID- 7735970
TI  - Ethanol exacerbates hepatic microvascular dysfunction, endotoxemia, and lethality
      in septic mice.
AB  - The effect of acute ethanol administration on the hepatic microvascular responses
      to sepsis was studied. Polymicrobial sepsis was induced 30 min after mice had
      received ethanol (1 g/kg b.w.) or isocaloric maltose-dextrin by gastric gavage.
      Lethality within 24 h was 91.7% in the ethanol-treated animals and 40.0% in
      septic controls. Endotoxin levels in ethanol treated animals were 107 pg/ml at 6
      hr and 1205 pg/ml at 12 h, compared with 32 pg/ml and 104 pg/ml, respectively in
      the controls. In vivo microscopy revealed that at 3 h in the ethanol treated
      septic animals, Kupffer cell phagocytic activity was increased by 41%, whereas
      the number of sinusoids containing blood flow were reduced by 34% concomitant
      with a 144% increase in the adherence of leukocytes to the sinusoidal walls when
      compared with the septic controls. By 6 h, however, Kupffer cell phagocytic
      activity was reduced by 48% in the ethanol treated animals; this was accompanied
      by a further deterioration in sinusoidal blood flow. Thus, a small, acute dose of
      ethanol causes significant impairment of the hepatic microcirculation followed by
      suppression of Kupffer cell activity. This results in exacerbation of endotoxemia
      and lethality during polymicrobial sepsis.

PMID- 7735971
TI  - The role of protein kinase C in lipopolysaccharide-induced myocardial depression
      in guinea pigs.
AB  - The effect of lipopolysaccharide (LPS) on cardiac protein kinase C (PKC)
      activation and cardiac depression was evaluated. Guinea pigs (n = 44) received
      intraperitoneal injections of saline or Escherichia coli LPS (2 mg/kg). Left
      atria were harvested 16 h later and suspended in oxygenated low calcium (1 mM) (n
      = 24) or high calcium (5 mM) (n = 20) 30 degrees C Krebs-Henseleit buffer. Atria
      were treated with H-7 (n = 23), a PKC inhibitor, or vehicle (n = 21). Contractile
      responses to changes in preload and stimulating frequency, in the resting and
      potentiated states, and to escalating doses of phenylephrine were measured. PKC
      activation in ventricular muscle was also determined. LPS activated ventricular
      PKC (p < .05) but treatment with H-7 failed to reverse LPS-induced atrial
      dysfunction in the low calcium buffer. Contractile function in the potentiated
      state indicated that LPS appears to interfere with calcium release from the
      sarcoplasmic reticulum (SR). The contractile response to phenylephrine was
      markedly attenuated in atria harvested from endotoxic animals. These data
      indicate that LPS-induced cardiac depression is mediated, in part, by alterations
      in SR calcium release. LPS activates cardiac PKC but a causal relationship among
      LPS, PKC, and cardiac dysfunction remains to be established.

PMID- 7735972
TI  - Effects of sepsis on recovery of the heart from 50 min ischemia.
AB  - Gram-negative sepsis as well as administration of agents that simulate or occur
      naturally subsequent to a septic challenge, can present as an oxidant stress to
      the myocardium. These stresses may then induce the development of protection of
      the heart from future stresses. This protection of the heart may occur in spite
      of the fact that sepsis itself induces myocardial dysfunction. In the present
      study we determined if sepsis is protective of a 50 min ischemic episode, one in
      which some degree of irreversible damage may occur. In addition we determined if
      sepsis-induced protection was still present when this ischemic challenge was
      imposed upon the heart of the alcoholic septic animal in which the chronic
      alcoholic state can lead to a potentiation of sepsis induced cardiac depression.
      Thus animals were fed an ethanol containing diet or a control diet for 8-10 weeks
      and were then made septic by the administration of Escherichia coli into the
      dorsal subcutaneous space. Control animals received sterile saline. The following
      day, hearts were studied in the isovolumic beating preparation and, after basal
      function was assessed, hearts were made globally ischemic for 50 min and
      reperfused for 30 min. Left ventricular pressure was continuously monitored and
      coronary flow was measured at specific intervals. After ischemia and reperfusion,
      hearts from control- and alcohol-fed animals that were nonseptic showed
      significantly decreased left ventricular performance. Ventricular pressure
      development of hearts from septic and alcoholic septic rats was not significantly
      decreased after ischemia and reperfusion compared to preischemia although
      preischemic function was significantly lower in the sepsis groups compared to
      their nonseptic control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735973
TI  - Differential alterations in cyclic nucleotide levels in Kupffer cells and
      hepatocytes following trauma-hemorrhage and resuscitation.
AB  - Although cyclic nucleotides play an important role in regulating the control of
      metabolism, it is not known whether there are any differential alterations in
      cyclic nucleotides in Kupffer cells and hepatocytes after trauma-hemorrhage and
      resuscitation. To study this, rats underwent laparotomy (i.e., trauma-induced)
      and were rapidly bled to and maintained at a mean arterial pressure of 40 mmHg
      until 40% of maximum bleedout volume was returned in the form of Ringer's
      lactate. The animals were then resuscitated with Ringer's lactate, equivalent to
      four times the volume of shed blood. At the time of maximum bleedout or at 1.5 h
      postresuscitation, a portion of the liver was removed, and the levels of cyclic
      adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were
      determined by radioimmunoassay. Moreover, Kupffer cells and hepatocytes were
      isolated in additional groups of animals and cAMP and cGMP levels were measured.
      The results indicate that hepatic cAMP decreased, whereas hepatic cGMP increased
      significantly at the time of maximum bleedout. Although resuscitation normalized
      hepatic cyclic nucleotide levels, the levels of cAMP and cGMP in Kupffer cells
      increased significantly at 1.5 h after resuscitation. In contrast, cAMP and cGMP
      levels in hepatocytes were not significantly different from shams under such
      conditions. Thus, differential alterations in cyclic nucleotide levels in
      different liver cell populations occur following trauma-hemorrhage and
      resuscitation.

PMID- 7735974
TI  - Bacterial translocation in cultured enterocytes: magnitude, specificity, and
      electron microscopic observations of endocytosis.
AB  - Previous in vivo evidence has shown that bacterial phagocytosis by enterocytes
      may be an initial step in bacterial translocation across the intestinal
      epithelium. This study analyzed the interactions of cultured enterocytes, namely
      Caco-2 cells, with nine strains of enteric bacteria, tested in pure culture and
      in mixed culture. These nine strains had a spectrum of invasive potential and
      included Salmonella typhimurium, Listeria monocytogenes (three strains),
      Escherichia coli (three strains), Proteus mirabilis, and Enterococcus faecalis.
      Numbers of viable intracellular bacteria recovered from Caco-2 cells were: L.
      monocytogenes > S. typhimurium > P. mirabilis > E. coli > E. faecalis. Uptake of
      a given microbe by enterocytes was strain-specific and was not influenced by the
      presence of another strain, regardless of the invasive ability of the coinfecting
      strain. Electron microscopic visualization of bacterial adherence and uptake by
      Caco-2 cells indicated that the epithelial interactions of normal enteric
      bacteria were similar to these observed with invasive strains of salmonella and
      listeria.

PMID- 7735975
TI  - Intestinal ischemia: reperfusion-mediated increase in hydroxyl free radical
      formation as reported by salicylate hydroxylation.
AB  - Oxygen free radicals may play a pivotal role in the development of the shock
      induced inflammatory response syndrome. Hydroxyl free radicals (.OH) react with
      salicylate (SA) to form 2,5- and 2,3-dihydroxybenzoic acid (DHBA) products. We
      utilized salicylate hydroxylation to investigate .OH formation during intestinal
      ischemia/reperfusion injury in male Sprague-Dawley rats. After administering
      salicylate, the superior mesenteric artery was occluded for 45 min and then
      allowed to reperfuse for 90 min after declamping. No significant changes in
      plasma 2,3- and 2,5-DHBA/SA ratios were observed in sham-operated or in animals
      given intestinal ischemia without reperfusion. A significant increase (p < .05)
      in arterial, venous, and portal venous 2,5-DHBA/SA ratios occurred 5 min after
      reperfusion. This increase was prevented by allopurinol as well as by
      dimethylthiourea (.OH scavenger) pretreatment. 2,3-DHBA was significantly
      increased (p < .05) in venous and portal venous blood after 30 min of
      reperfusion, but was not detectable in plasma of allopurinol- and
      dimethylthiourea-treated rats. These results indicate that hydroxyl free radical
      formation as reported by SA hydroxylation appears to be important in intestinal
      ischemia/reperfusion-related tissue injury.

PMID- 7735976
TI  - Endothelin-1 as a regulator of hepatic microcirculation: sublobular distribution
      of effects and impact on hepatocellular secretory function.
AB  - Endothelin-1 is a potent vasoconstrictor in the portal circulation causing
      sinusoidal constriction as well as presinusoidal resistance changes. Using in
      vivo videomicroscopy we studied the sublobular differences in dose response
      characteristics of sinusoid constriction at 10-13 min into continuous infusion of
      5, 1.0, 3.0, and 5.0 pmol of endothelin-1 (ET-1)/100 g body weight/min in
      pentobarbital anesthetized rats. In addition, bile flow was monitored to estimate
      parenchymal secretory function. ET-1 evoked a profound constrictor effect in both
      sublobular regions studied. However, the maximal decrease of sinusoidal width in
      periportal inflow region (zone 1; 1 pmol/100 g/min: 4.8 +/- .1 microns) was
      reached at slightly lower concentrations of the peptide than in pericentral
      outflow region (zone 3; 3 pmol/100 g/min: 6.2 +/- .3 microns) compared to
      respective baseline values (zone 1: 7.1 +/- .1 microns; zone 3: 10.2 +/- .1
      microns), suggesting upstream binding and clearance of the peptide. The
      constrictor response in zone 1 was biphasic and at higher concentrations of the
      peptide (5 pmol/100 g/min: 5.5 +/- .2 microns) sinusoidal widths increased again
      compared to the maximal response with the 1 pmol. Secretory function as reflected
      by the bile flow was maintained or even slightly increased with the lower doses
      (.5 and 1 pmol) of ET-1 and during the first 10 min into infusion of the higher
      doses (3 and 5 pmol). Subsequently, an approximately 20-25% decrease in bile flow
      accompanied the infusion of higher doses of ET-1.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7735977
TI  - T-lymphocyte Ca2+ signalling and proliferative responses during sepsis.
AB  - Alterations in T-lymphocyte kinetics and/or activation have been implicated in
      burn and traumatic injury. This study evaluated concanavalin A (Con A) regulation
      of both intracellular Ca2+ (Ca2+i) and proliferation in T-lymphocytes harvested
      from spleens of septic rats. Rats were implanted with fecal pellets containing
      Escherichia coli (150 colony forming units (CFU)) and Bacteroides fragilis (10(4)
      CFU). T-cell [Ca2+]i was measured before and after treatment of cells with Con A,
      using Fura-2 and microfluorophotometry. Splenic lymphocytes were cultured for 72
      h with Con A to assess their proliferative response. As compared to sterile
      implanted rats, the septic rat T-lymphocytes Ca2+i response to ConA significantly
      decreased on days 1 and 2 after implantation. A significant decrease in T-cell
      proliferative response to Con A, compared to sterile controls, was found in
      septic rats on day 2 but not on day 1. These results suggest that Con A-mediated
      proliferation in T-cells occurs secondarily to a decrease in cellular Ca2+
      signalling. The depression in the T-cell proliferative response during sepsis
      could contribute to a decrease in host's resistance against sepsis.

PMID- 7735978
TI  - Hepatic intercellular communication in shock and inflammation.
AB  - The liver is well recognized as a target for injury during low flow or
      inflammatory states. Functionally, the result is both metabolic and host defense
      dysfunction. Although the liver is clearly responsive to changes in systemic
      levels of various mediators, it is becoming apparent that substantial changes
      occur within the liver that are not directly dependent on extrahepatic factors.
      This is the result of complex interactions among the various cell types that
      exist in a highly organized arrangement within the functional subunit of the
      liver. The purpose of this review is to summarize the structural relationships
      which form the basis for this system of cell-cell communication and their
      functional implications both in the normal liver and during both low-flow and
      normal-flow inflammatory states.

PMID- 7735979
TI  - Anti-tumor necrosis factor antibody treatment of recurrent bacteremia in a baboon
      model.
AB  - Timely intervention in recurrent episodes of sepsis poses a major problem in
      intensive care, because the diagnosis is often made after the onset of sepsis,
      delaying the initiation of treatment. There are only a few animal models that
      cover this situation. We have developed a baboon model of recurrent bacteremia (3
      x 2 h intravenous infusion of 1 x 10(8) CFU Escherichia coli/kg), which leads to
      late organ failure. In this model (tested on 16 animals) we began anti-tumor
      necrosis factor antibody treatment (BAYX 1351; Bayer AG, 7.5 mg/kg or saline
      placebo) after the first bacteremic episode (+4 h), which significantly (p < .05)
      protected animals from death, none out of eight (100% survival), in the treatment
      group in contrast to four animals out of eight died (50% survival) in the placebo
      group. This effect was also reflected in improved organ function and in
      attenuated cytokine and plasminogen activator inhibitor release. From these
      studies we conclude that the delayed application of anti-tumor necrosis factor
      antibodies in recurrent bacteremia is a powerful tool for preventing septic
      death.

PMID- 7735980
TI  - Effects of trauma on immune cell function: impairment of intracellular calcium
      signaling.
AB  - Immunosuppression following injury influences infectious morbidity and mortality.
      Impaired T-cell activation conceding to inadequate antigen recognition
      contributes to this immunosuppression. Successful activation and proliferation of
      T-cells requires precisely specified levels of intracellular calcium thresholds
      and peak signals. The purpose of this study was to evaluate intracellular calcium
      signaling following injury. Hospitalized blunt and penetrating trauma patients in
      a Level 1 Trauma Center following injury and sepsis were tested for immune cell
      calcium signaling. Peripheral blood mononuclear cells (PBMC) were isolated and
      calcium signaling tested with Fura-2 AM. PBMC from trauma patients had
      significantly depressed values of baseline, peak and sustained levels of
      intracellular calcium prior to and following phytohemagglutinin stimulation when
      compared to normal controls. This deficit in intracellular calcium signaling is
      more severe in septic trauma patients (60% reduction). Suppression of calcium
      signaling appears to be mediated by at least, in part, circulating serum factors.
      Prostaglandin E2 seems to have a limited contribution to this effect as it is
      suppressive only when in direct contact with PBMC. Immune cell activation failure
      can in part be explained by the inadequacy of calcium signaling; restoration of
      immunocompetence following trauma will have to be addressed by strategies to
      restore calcium signaling, a vital step necessary for T-cell proliferation
      following antigen recognition.

PMID- 7735981
TI  - Bacterial translocation and lipopolysaccharide-induced mortality in genetically
      macrophage-deficient op/op mice.
AB  - Genetically macrophage-deficient op/op mice have a total absence of macrophage
      colony-stimulating factor (also known as colony-stimulating factor 1 or CSF-1),
      and therefore an absence of a population of macrophages dependent on CSF-1. op/op
      mice also have profound secondary deficiencies in certain cytokines secreted by
      this macrophage population, such as tumor necrosis factor, interleukin-1, and
      granulocyte colony-stimulating factor. In the present study, op/op mice were used
      to clarify the role of the macrophage in two clinical processes: (a) bacterial
      translocation in response to antibiotic-induced intestinal overgrowth, and (b)
      endotoxin-induced bacterial translocation, morbidity, and mortality. The results
      were unexpected, in that bacterial translocation and endotoxin-induced morbidity
      and mortality were similar in op/op mice and their functionally normal
      littermates. These data indicated either that a specific macrophage population
      and its cytokines (including tumor necrosis factor and interleukin 1) might not
      play pivotal roles in the pathogenesis of bacterial translocation and endotoxin
      induced septic shock, or alternatively, as yet unknown redundancies in vivo might
      compensate for the genetic deficiencies associated with the op/op mutation.

PMID- 7735982
TI  - Effect of ethanol and sodium arsenite on HSP-72 formation and on survival in a
      murine endotoxin model.
AB  - Recently, investigators reported that prophylactic hyperthermia and induction of
      heat shock proteins (HSPs) decreased mortality from endotoxin. Although the
      mechanism by which hyperthermia protects is unknown, two possible etiologies are
      induction of HSPs and/or production of cytokines, interleukin-1 alpha (IL-1
      alpha) or tumor necrosis factor-alpha (TNF-alpha). The purpose of this study was
      to determine if in vivo administration of sodium arsenite (NaAsO2) or ethanol,
      inducers of HSPs in isolated cells, induced HSP-72 production in lung, liver,
      kidney, and duodenum (organs known to induce HSP-72 by heat) and improved
      survival from endotoxin. Female ND4 mice were injected intraperitoneally with
      either NaAsO2 (5.25 mg/kg body weight) or ethanol (4.0 g/kg), immediately, 8 or
      18 h prior to Escherichia coli endotoxin injection (20 mg/kg). Both compounds
      improved short-term (24 h) survival twofold (p < .01), but failed to improve long
      term (7 days) survival. Simultaneous injection of ethanol with endotoxin improved
      both short-term survival twofold (p < .01), and long-term survival 5-fold (p <
      .001). Ethanol induced HSP-72 in kidney, 50% that of the standard (i.e., pooled
      livers isolated from heat-treated mice); NaAsO2 induced HSP-72 in kidney
      (approximately 50% of standard) and liver (approximately 21% of standard).
      Neither ethanol nor NaAsO2 alone increased circulating concentrations of IL-1
      alpha or TNF-alpha. However, ethanol given concurrently with endotoxin produced a
      significant decrease in TNF-alpha compared to endotoxin alone (p < .01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7735983
TI  - Beneficial effect of H2-agonism and H1-antagonism in rat endotoxic shock.
AB  - Although histamine release is generally considered harmful in endotoxic shock,
      several data exist to doubt this view. Own previous studies in rats let us assume
      a possible beneficial effect only with H1-antagonists, however a detrimental
      effect on survival with H2-antagonists. Consequently H1- and H2-agonists and
      antagonists were studied to prove the hypothesis of a beneficial H2-agonistic and
      H1-antagonistic effect. Two randomized studies were performed in a standardized
      rat endotoxic shock model (45 mg of Escherichia coli endotoxin/kg body weight
      (b.w.)). In both, methylprednisolone (50 mg/kg b.w.) and saline were used as
      positive and negative controls, respectively. Study I compared the effects of H1-
      and H2-agonists (betahistine, .1 mg/kg/h, and impromidine, 100 micrograms/kg/h)
      with H1- and H2-antagonists (astemizole and famotidine both 1 mg/kg b.w.; 20
      rats/dose). Study II was performed to estimate the dose-response relationship of
      a new, highly potent H2-agonist with additional H1-antagonistic features (BU-E
      75: .01, .1, 1.0, 10, and 100 micrograms/kg/h; 20 rats/dose). Animals receiving
      impromidine or BU-E 75 all received omeprazole (1 mumol/kg b.w.) to suppress
      gastric acid secretion. In study I impromidine significantly increased the
      survival-time and -course compared to famotidine treated animals (p = .01 and p <
      .05). Study II showed a positive dose-response relationship of BU-E 75 with an
      increase in survival rates from 30% (.01 microgram/kg/h) to 70% (100
      micrograms/kg/h). These data strongly support the hypothesis of a beneficial
      effect of H2-agonism and H1-antagonism on survival parameters in rat endotoxic
      shock.

PMID- 7735984
TI  - The role of platelet-activating factor in alterations of system A amino acid
      transport in rat soleus and extensor digitorum longus muscles during endotoxic
      shock.
AB  - We investigated the role of platelet-activating factor (PAF) as a mediator of
      system A amino acid transport alterations in skeletal muscle during endotoxic
      shock. Male Sprague-Dawley rats (80-100 g) were injected with Salmonella
      enteritidis endotoxin (10 mg/kg intravenously (i.v.)) or PAF (4 micrograms/kg
      i.v.) and killed 5 or 1 h later, respectively. Control rats were injected with a
      vehicle. System A amino acid transport was assessed by measuring the cellular
      uptake of 1-14C-alpha-aminoisobutyric acid (AIB, amino acid analog) in isolated
      soleus and extensor digitorum longus (EDL) muscles, in vitro. AIB uptake in
      soleus and EDL from endotoxic rats was approximately 33% lower than control
      muscles. The i.v. injection of PAF reduced AIB uptake 9% in soleus and 15% in EDL
      as compared with muscles from control rats. The prophylactic administration of
      WEB 2086 (30 mg/kg i.v.), a PAF receptor antagonist, attenuated the endotoxin
      induced inhibition of amino acid transport by 26% in EDL and 17% in soleus. PAF
      (1 microgram/mL) added to incubation media had no effect on AIB uptake in soleus
      and EDL of control rats. However, there was a reduction in AIB uptake in soleus
      and EDL obtained from rats 1 h after an i.v. injection of PAF (4 micrograms/kg)
      and after incubation in media containing PAF (1 microgram/mL). Addition of plasma
      to incubation media obtained from rats 1 h after the i.v. injection of endotoxin
      or PAF attenuated AIB uptake in soleus and EDL of control rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7735985
TI  - Centrally mediated influences of hypertonic NaCl and angiotensin II on regional
      blood flow and hemodynamic responses to hypotensive hemorrhage in conscious
      sheep.
AB  - The influence of separate and combined intracerebroventricular (ICV) infusions of
      hypertonic (.5 M) NaCl (HTNa) at .02 mL min-1 and angiotensin II (ANG II) at 1
      pmol kg-1 min-1 on tolerance to hemorrhage, accompanying systemic hemodynamic
      changes, and regional blood flow was studied in adult conscious sheep.
      Corresponding measurements during ICV .9% NaCl served as controls. The hemorrhage
      volume needed to lower the blood pressure to about 50 mmHg was significantly
      larger during treatment with HTNa and HTNa/ANG II (27.8 +/- 2.2 and 28.3 +/- 2.5
      mL kg-1, respectively; p < .001; about 45% of estimated blood volume) as well as
      during ANG II (20.1 +/- 1.3 mL kg-1; p < .01) compared to controls (15.1 +/- .7
      mL kg-1; about 25% of estimated blood volume). In spite of a larger hemorrhage
      volume, the lowering of the cardiac output was not accentuated, and its
      subsequent recovery was not impaired during ICV infusion of HTNa or HTNa/ANG II.
      Similarly, the posthemorrhage restoration of the systemic blood pressure was not
      negatively affected by the more pronounced hypovolemia induced during the ICV
      treatments compared to controls. In contrast to ANG II, HTNa infusion, alone or
      in combination with ANG II, was accompanied by a significantly lower renal blood
      flow, and a higher renovascular resistance, during the posthemorrhage period. The
      femoral blood flow was maintained or even slightly elevated after hemorrhage in
      all experiments. The integrated results of the study imply differentiated
      hemodynamic effects of centrally administered HTNa and ANG II.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7735986
TI  - Systemic and portal prostacyclin and thromboxane response to hemorrhage in portal
      hypertension.
AB  - Prostacyclin (PGI2) and thromboxane (Tx-A2) levels increase in hemorrhagic shock.
      Prostanoids have been implicated as mediators of the systemic and splanchnic
      hyperemia characteristic of portal hypertension (PHT). We hypothesized that
      prostanoid pharmacokinetics could be altered during shock in PHT and mediate the
      poor tolerance of PHT animals to hemorrhage. Hemodynamics and PGI2 and Tx-A2
      levels were determined in portal, systemic venous, and arterial vascular beds at
      baseline and following hemorrhage and resuscitation. Portal and systemic PGI2
      levels were elevated at baseline in PHT animals, with no change in resting Tx-A2.
      Following hemorrhage, PGI2 and Tx-A2 levels increased in normal animals, but were
      unchanged in PHT. Portal hypertension PGI2 production was elevated at rest, while
      Tx-A2 levels were diminished. There is a diminished prostanoid response to
      hemorrhage in PHT animals compared to normal. This abnormality in prostanoid
      pharmacokinetics may contribute to the abnormal response to hemorrhage in PHT.

PMID- 7735988
TI  - [Necrotizing enterocolitis].

PMID- 7735987
TI  - High volume hemofiltration improves hemodynamics and survival of pigs exposed to
      gut ischemia and reperfusion.
AB  - This study assesses the influence of high volume continuous hemofiltration on
      hemodynamics of pigs subjected to bowel ischemia/reperfusion. Twelve anesthetized
      and ventilated pigs were studied for 60 min during clamping of the superior
      mesenteric artery (SMA) and subsequently for 90 min after release of the clamp,
      while measuring global hemodynamics, SMA flow, and jejunal pCO2. They were
      randomly divided into two groups: pigs in "control" group were subjected to SMA
      clamping only. Pigs in "hemofiltered" group received zero-balanced, high volume,
      veno-venous hemofiltration with the removal of 6000 ml of ultrafiltrate/h,
      starting 30 min before clamping until 90 min after removal of the SMA clamp.
      Thereafter, pigs were allowed to awake and sacrificed after 24 h for macroscopic
      assessment of bowel damage. The drop in cardiac output (CO) during SMA clamping
      in the hemofiltered group was 2.5 +/- .3 L/min (mean +/- SE) (1.1/4.0; 95%
      confidence interval) smaller than in the control group. At the end of the
      experiment, mean arterial pressure (MAP) in the hemofiltered group was 33 +/- 6
      (19/48) mmHg higher than in the control group, CO was 2.0 +/- .2 (1.2/2.8) L/min
      higher in the hemofiltered group. After 60 min of SMA clamping, left ventricular
      stroke work in the hemofiltered group was 35 +/- 4 (14/56) g higher than in the
      control group, and higher by 33 +/- 3 (21/46) g at 90 min after release of the
      SMA clamp. The mean pulmonary artery pressure, right atrial pressure, pulmonary
      artery wedge pressure, SMA flow and bowel wall pCO2 at different time points did
      not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7735989
TI  - [Ileocecal syndrome].

PMID- 7735990
TI  - [Brown bowel syndrome].

PMID- 7735991
TI  - [Ulcerative colitis].

PMID- 7735992
TI  - [Hamartomatous polyp and hamartomatous polyposis].

PMID- 7735993
TI  - [Familial adenomatous polyposis].

PMID- 7735994
TI  - [Colorectal cancer with family history].

PMID- 7735995
TI  - [Irritable bowel syndrome].

PMID- 7735996
TI  - [Chagas' disease (Cruz's disease)].

PMID- 7735997
TI  - [Granular cell tumor].

PMID- 7735998
TI  - [Malabsorption syndrome].

PMID- 7735999
TI  - [Tubular duplication of the colon].

PMID- 7736000
TI  - [Intestinal pseudo-obstruction].

PMID- 7736001
TI  - [Pseudomembranous enterocolitis].

PMID- 7736002
TI  - [Acute hemorrhagic rectal ulcer syndrome; AHRUS].

PMID- 7736003
TI  - [Acute rectal mucosal lesion].

PMID- 7736004
TI  - [Ischemic colitis and gangrenous ischemic colitis].

PMID- 7736005
TI  - [Gastrointestinal perforation by ingested fish bones].

PMID- 7736006
TI  - [Chilaiditi's syndrome].

PMID- 7736007
TI  - [Megacolon syndrome].

PMID- 7736008
TI  - [Diversion colitis and proctitis].

PMID- 7736009
TI  - [Chlamydia trachomatis proctitis].

PMID- 7736010
TI  - [Advanced colon cancer and advanced rectal cancer].

PMID- 7736011
TI  - [Diarrhea (acute and chronic)].

PMID- 7736012
TI  - [Protozoan and helminthic infection].

PMID- 7736013
TI  - [Multiple primary carcinomas in the jejunum, ileum, colon and rectum].

PMID- 7736014
TI  - [Intestinal complications of collagen vascular diseases].

PMID- 7736015
TI  - [Crohn's disease].

PMID- 7736016
TI  - [Eosinophilic enterocolitis].

PMID- 7736017
TI  - [Intestinal tuberculosis].

PMID- 7736018
TI  - [Antibiotics-associated colitis--Clostridium difficile colitis].

PMID- 7736019
TI  - [Ossification in intestinal carcinoma].

PMID- 7736020
TI  - [Cholera].

PMID- 7736021
TI  - [Bacterial food poisoning].

PMID- 7736022
TI  - [Shigellosis].

PMID- 7736023
TI  - [Atonic constipation].

PMID- 7736024
TI  - [Juvenile polyposis coli].

PMID- 7736025
TI  - [Duodenocolic fistula].

PMID- 7736026
TI  - [Hemorrhagic colitis].

PMID- 7736027
TI  - [Cronkhite-Canada syndrome].

PMID- 7736028
TI  - [Cancer of the small intestine].

PMID- 7736030
TI  - [Arteriomesenteric-occulusion of the duodenum].

PMID- 7736029
TI  - [Squamous cell carcinoma of the small bowel, colon and rectum].

PMID- 7736031
TI  - [Diverticulum and diverticulosis of the small intestine].

PMID- 7736032
TI  - [Intestinal carcinoma with serosal invasion].

PMID- 7736033
TI  - [Colitis cystica profunda].

PMID- 7736034
TI  - [Adult spontaneous volvulus of the sigmoid colon].

PMID- 7736035
TI  - [Celiac disease].

PMID- 7736036
TI  - [Annular carcinoma of the colon].

PMID- 7736037
TI  - [Cancer in adenoma].

PMID- 7736038
TI  - [Adenoma-carcinoma sequence].

PMID- 7736039
TI  - [Congenital intestinal atresia and stenosis].

PMID- 7736040
TI  - [de novo cancer].

PMID- 7736041
TI  - [Early carcinoma of the intestine and intramucosal carcinoma].

PMID- 7736042
TI  - [Mucosal bridge of the colon].

PMID- 7736043
TI  - [Hemangiopericytoma of the colon].

PMID- 7736045
TI  - [Inflammatory polyp and polyposis of colon and rectum].

PMID- 7736044
TI  - [Transitional polyp of colon and rectum].

PMID- 7736046
TI  - [Metaplastic (hyperplastic) polyp and polyposis of the colon].

PMID- 7736047
TI  - [Experimental colitis induced by dextran sulfate].

PMID- 7736048
TI  - [Carcinoma of the colon and rectum involving the urinary bladder].

PMID- 7736049
TI  - [Diverticular disease and diverticulitis of the colon].

PMID- 7736050
TI  - [Gastrointestinal abnormalities in alpha-chain disease].

PMID- 7736051
TI  - [Neoplastic polyp of the large intestine and polyposis (tubular adenoma and
      tubulovillous adenoma)].

PMID- 7736052
TI  - [Large intestinal carcinoma associated with cancers of the other organs and
      double cancer of the large intestine and stomach].

PMID- 7736053
TI  - [Nodule-aggregating lesion of the large intestine (colorectal flat elevation with
      conglomerated nodular surface)].

PMID- 7736054
TI  - [Benign lymphoid polyp and polyposis].

PMID- 7736055
TI  - [Simple ulcer of the intestine].

PMID- 7736056
TI  - [Short bowel syndrome].

PMID- 7736057
TI  - [Gardner's syndrome].

PMID- 7736058
TI  - [Protein-losing gastroenteropathy].

PMID- 7736059
TI  - [Angiodysplasia of the intestine].

PMID- 7736060
TI  - [Dieulafoy's ulcer of intestine].

PMID- 7736061
TI  - [Intestinal goblet cell mucus release].

PMID- 7736062
TI  - [Inflammatory fibroid polyp of the intestine].

PMID- 7736063
TI  - [Linitis plastica type of carcinoma of the intestine].

PMID- 7736064
TI  - [Lipohyperplasia of the ileocecal valve].

PMID- 7736065
TI  - [Intestinal lipoid granuloma].

PMID- 7736066
TI  - [Malignant lymphoma of mucosa-associated lymphoid tissue (MALT) arising from the
      intestines].

PMID- 7736067
TI  - [Hirschsprung's disease, neuronal intestinal dysplasia, hypoganglionosis].

PMID- 7736068
TI  - [Multiple lymphomatous polyposis].

PMID- 7736069
TI  - [Pleomorphic giant cell carcinoma of the intestine].

PMID- 7736070
TI  - [Spindle cell tumor of the intestine].

PMID- 7736071
TI  - [Vanishing tumor of the intestine].

PMID- 7736072
TI  - [Intestinal vascular ectasia].

PMID- 7736073
TI  - [Malignant fibrous histiocytoma].

PMID- 7736074
TI  - [Heterotopic (ectopic) gastric mucosa].

PMID- 7736076
TI  - [Signet-ring cell carcinoma of colon].

PMID- 7736075
TI  - [Foreign body of the intestine].

PMID- 7736077
TI  - [Indeterminate colitis].

PMID- 7736078
TI  - [Enterocolitis].

PMID- 7736080
TI  - [Hamartoma of the intestine].

PMID- 7736079
TI  - [Malrotation].

PMID- 7736081
TI  - [Carcinoid tumor of the intestine].

PMID- 7736082
TI  - [Intestinal amyloidosis and amyloid colitis].

PMID- 7736083
TI  - [Intestinal Behcet's disease].

PMID- 7736084
TI  - [Pneumatosis cystoides intestinalis; PCI].

PMID- 7736085
TI  - [Duplications of the alimentary canal].

PMID- 7736086
TI  - [Mesenteric vascular insufficiency].

PMID- 7736087
TI  - [Arterio venous malformation of bowel tract].

PMID- 7736088
TI  - [Ulcer formation at intestinal anastomotic site].

PMID- 7736089
TI  - [Colon cancer with the sign of Leser-Trelat].

PMID- 7736090
TI  - [Obstructing carcinoma of the intestine].

PMID- 7736091
TI  - [Perforative carcinoma of the intestine].

PMID- 7736092
TI  - [Mesenteric cyst].

PMID- 7736093
TI  - [Intestinal teratoma].

PMID- 7736094
TI  - [Incomplete intestinal obstruction].

PMID- 7736095
TI  - [Fistula of enteric diverticulum].

PMID- 7736096
TI  - [Vascular tumors of the intestine].

PMID- 7736097
TI  - [Intestinal hemangioendothelioma].

PMID- 7736098
TI  - [Enterolithiasis].

PMID- 7736099
TI  - [MRSA enteritis].

PMID- 7736101
TI  - [Intestinal malignant melanoma].

PMID- 7736100
TI  - [Intestinal eosinophilic granuloma].

PMID- 7736102
TI  - [Intestinal geotrichosis].

PMID- 7736103
TI  - [Enteric endometriosis].

PMID- 7736104
TI  - [Lipoma and liposarcoma of the jejunum, ileum, coecum, colon and rectum].

PMID- 7736105
TI  - [Intussusception in children and adult].

PMID- 7736106
TI  - [Villous adenoma].

PMID- 7736107
TI  - [Unclassified tumors of intestine].

PMID- 7736108
TI  - [Tumors of the intestine (benign, malignant: epithelial, non-epithelial)].

PMID- 7736109
TI  - [Small cell (neuroendocrine) carcinoma of the intestine].

PMID- 7736110
TI  - [Intestinal varices].

PMID- 7736111
TI  - [Peutz-Jeghers syndrome].

PMID- 7736112
TI  - [Mycosis of the intestine].

PMID- 7736113
TI  - [Neurogenic tumor of small and large intestine].

PMID- 7736114
TI  - [Intestinal aganglionosis and intestinal segmental oligoganglionosis].

PMID- 7736115
TI  - [Fibrolipoma (lipoma) of the intestine].

PMID- 7736116
TI  - [Adenocarcinoma of the intestine].

PMID- 7736117
TI  - [Perforation of the intestine].

PMID- 7736118
TI  - [Adenoma (tubular adenoma, tubulo villous adenoma, villous adenoma, and
      adenomatosis)].

PMID- 7736119
TI  - [Adenosquamous carcinoma of the intestine].

PMID- 7736120
TI  - [Embryonal carcinoma of the intestine].

PMID- 7736122
TI  - [Typhoid fever].

PMID- 7736121
TI  - [Enterovaginal fistula (enterouterine fistula)].

PMID- 7736123
TI  - [Intestinal cancer with peritoneal metastasis].

PMID- 7736124
TI  - [Poorly differentiated carcinoma of intestine].

PMID- 7736125
TI  - [Endocrine cell carcinoma of the intestine].

PMID- 7736126
TI  - [Mucinous carcinoma of the intestine].

PMID- 7736127
TI  - [Submucosal tumor of the intestine].

PMID- 7736128
TI  - [Enterogenous cyst].

PMID- 7736129
TI  - [Intraabdominal abscess due to intestinal perforation].

PMID- 7736130
TI  - [Colorectal paraffinoma].

PMID- 7736131
TI  - [Enterocutaneous fistula].

PMID- 7736132
TI  - [Smooth muscle tumor of the intestine].

PMID- 7736133
TI  - [Intestinal obstruction].

PMID- 7736135
TI  - [Intramural hematoma of the small intestine].

PMID- 7736134
TI  - [Sigma elongatum and dolichosigma].

PMID- 7736136
TI  - [Vesicoentric fistula].

PMID- 7736137
TI  - [Actinomycosis of intestine].

PMID- 7736138
TI  - [Colonic polyp and polyposis].

PMID- 7736139
TI  - [Intestinal malakoplakia].

PMID- 7736140
TI  - [Intestinal undifferentiated carcinoma].

PMID- 7736141
TI  - [Heterotopic pancreas in the intestine].

PMID- 7736142
TI  - [Tubo-intestinal fistula].

PMID- 7736143
TI  - [Elevated lesion of intestine].

PMID- 7736144
TI  - [Intestinal lymphangiectasia].

PMID- 7736145
TI  - [Intestinal changes in Schonlein-Henoch purpura].

PMID- 7736146
TI  - [Lymphangioma of the colon and mesenteric cyst].

PMID- 7736147
TI  - [Lymphoid hyperplastic diseases of the intestine, lymphoid hyperplasia of the
      intestine, malignant lymphoma of the intestine, and Burkitt's lymphoma of the
      intestine].

PMID- 7736148
TI  - [Solitary ulcer syndrome of the rectum].

PMID- 7736149
TI  - [Rectocele].

PMID- 7736150
TI  - [Mucosal prolapse syndrome of the rectum].

PMID- 7736152
TI  - [Metastatic neoplasms of the bowel].

PMID- 7736151
TI  - [Barium granuloma of the rectum].

PMID- 7736153
TI  - [Idiopathic megacolon].

PMID- 7736154
TI  - [Idiopathic constipation].

PMID- 7736155
TI  - [Turcot's syndrome].

PMID- 7736156
TI  - [Myxedema megacolon].

PMID- 7736157
TI  - [Nonspecific multiple ulcers of the small intestine].

PMID- 7736158
TI  - [Non-occlusive mesenteric ischemia].

PMID- 7736160
TI  - [Splenic flexure syndrome].

PMID- 7736159
TI  - [Diffusely infiltrating carcinoma of the colon].

PMID- 7736161
TI  - [Abdominal wall involvement in carcinoma of the colon].

PMID- 7736162
TI  - [Indeterminate colitis].

PMID- 7736163
TI  - [Obstructive colitis].

PMID- 7736164
TI  - [Flat & depressed type tumor].

PMID- 7736165
TI  - [WDHA syndrome].

PMID- 7736166
TI  - [Constipation].

PMID- 7736167
TI  - [Phlegmonous enterocolitis].

PMID- 7736168
TI  - [Radiation enteritis].

PMID- 7736169
TI  - [Radiation-induced cancer of the intestine].

PMID- 7736170
TI  - [Melanosis coli].

PMID- 7736171
TI  - [Blind loop syndrome].

PMID- 7736172
TI  - [Pericecal abscess].

PMID- 7736173
TI  - [Polypoid type of early colorectal cancer].

PMID- 7736174
TI  - [Acute appendicitis].

PMID- 7736175
TI  - [Tubercular appendicitis].

PMID- 7736176
TI  - [Duplication of vermiform appendix].

PMID- 7736177
TI  - [Crohn's disease of the appendix].

PMID- 7736178
TI  - [Appendiceal-sigmoid fistula].

PMID- 7736179
TI  - [Metaplastic polyp of the appendix vermiformis].

PMID- 7736180
TI  - [Carcinoid tumor of the appendix].

PMID- 7736181
TI  - [Diverticulitis of the vermiform appendix].

PMID- 7736182
TI  - [Appendiceal calculi].

PMID- 7736183
TI  - [Endometriosis of the vermiform appendix].

PMID- 7736184
TI  - [Villous adenoma of the appendix].

PMID- 7736185
TI  - [Tumors of the appendix (epithelial, non-epithelial, benign and malignant)].

PMID- 7736186
TI  - [Adenocarcinoma].

PMID- 7736187
TI  - [Aphthoid colitis, aphthous lesions of the colon].

PMID- 7736188
TI  - [Adenoma of appendix].

PMID- 7736189
TI  - [Metastatic carcinoma of the appendix].

PMID- 7736190
TI  - [Granuloma of the vermiform appendix].

PMID- 7736191
TI  - [Appendiceal mucocele].

PMID- 7736192
TI  - [Mucinous cystadenocarcinoma of the vermiform appendix].

PMID- 7736193
TI  - [Mucinous cystadenoma of the vermiform appendix].

PMID- 7736194
TI  - [Appendiceal abscess].

PMID- 7736195
TI  - [Polypoid lesion of the appendix].

PMID- 7736196
TI  - [Lymphoid hyperplasia of the appendix].

PMID- 7736197
TI  - [Anal lesions observed in Crohn's disease].

PMID- 7736198
TI  - [Enterocele].

PMID- 7736199
TI  - [Outlet obstruction syndrome].

PMID- 7736200
TI  - [Allergic enteritis].

PMID- 7736202
TI  - [Ectopic anus].

PMID- 7736201
TI  - [Spastic levator syndrome].

PMID- 7736203
TI  - [Familial imperforate anus].

PMID- 7736204
TI  - [Tuberculous anal ulcer].

PMID- 7736205
TI  - [Anal ulcer].

PMID- 7736206
TI  - [Anal incontinence].

PMID- 7736207
TI  - [Cloacogenic carcinoma with reference to malignant tumors of the anal canal].

PMID- 7736208
TI  - [Infectious diseases in anus].

PMID- 7736209
TI  - [Endocrine cell carcinoma of the anal canal].

PMID- 7736210
TI  - [Pruritus ani].

PMID- 7736211
TI  - [Periproctal abscess].

PMID- 7736212
TI  - [Periproctal abscess with chronic granulomatous disease].

PMID- 7736213
TI  - [Metachronous malignancies of the intestine (especially, metachronous colorectal
      cancer)].

PMID- 7736214
TI  - [Tumors of anus, benign epithelial, benign non-epithelial, malignant epithelial
      and malignant non-epithelial].

PMID- 7736215
TI  - [Tumor-like lesions of the anus].

PMID- 7736216
TI  - [Cryptitis].

PMID- 7736217
TI  - [Adenocarcinoma and mucinous carcinoma of the anal canal].

PMID- 7736218
TI  - [Peri-anal condyloma acuminatum and giant condyloma acuminata].

PMID- 7736219
TI  - [Adenosquamous carcinoma of the anal canal].

PMID- 7736220
TI  - [Anal papillitis].

PMID- 7736221
TI  - [Perianal Bowen's disease].

PMID- 7736222
TI  - [Perianal endometriosis].

PMID- 7736223
TI  - [Perianal Paget's disease].

PMID- 7736224
TI  - [Atypical condyloma latum of anus].

PMID- 7736225
TI  - [Injury of anal region].

PMID- 7736226
TI  - [Perineal hidradenitis suppurativa].

PMID- 7736227
TI  - [Squamous cell carcinoma of the anal canal].

PMID- 7736228
TI  - [Undifferentiated carcinoma of the anal region].

PMID- 7736229
TI  - [Giant cell carcinoma originated from the heterotopic pancreas].

PMID- 7736230
TI  - [Anal malignant melanoma].

PMID- 7736231
TI  - [Basaloid carcinoma of anal canal].

PMID- 7736232
TI  - [Supralevator abscess].

PMID- 7736233
TI  - [Anal atresia].

PMID- 7736234
TI  - [Hemorrhoid].

PMID- 7736235
TI  - [Anorectal fistula].

PMID- 7736236
TI  - [Fistula-cancer].

PMID- 7736237
TI  - [Skin tag].

PMID- 7736238
TI  - [Anal prolapse].

PMID- 7736239
TI  - [Anorectal malformations].

PMID- 7736240
TI  - [Hereditary solitary polyps (adenoma) of the colon].

PMID- 7736241
TI  - [Phantom anal phenomena following amputation of the rectum].

PMID- 7736242
TI  - [Rectal prolapse and concealed prolapse].

PMID- 7736243
TI  - [Rectovaginal fistula].

PMID- 7736244
TI  - [Mucosal prolapse syndrome of the rectum].

PMID- 7736245
TI  - [Intraepithelial cancer of the anal canal].

PMID- 7736246
TI  - [Hereditary non-polyposis colorectal cancer: HNPCC].

PMID- 7736247
TI  - [Cellulitis].

PMID- 7736248
TI  - [Pilonidal disease].

PMID- 7736249
TI  - [Anal fissure].

PMID- 7736250
TI  - [Stage classification of esophageal, gastric and colorectal cancer].

PMID- 7736251
TI  - [Viral gastroenteritis].

PMID- 7736252
TI  - [Inflammatory bowel disease].

PMID- 7736253
TI  - [Inflammatory intestinal tumor].

PMID- 7736254
TI  - [Andre Lwoff (1902-1994)].

PMID- 7736255
TI  - [Development of molecular biomarkers for the detection of nonbiocompatible
      substances in the environment].
AB  - Many difficult issues confront toxicologists. For instance, animal studies have
      proved to be difficult for the assessment of human toxicity especially to measure
      directly the impact of low doses of toxic compounds. Recently, novel molecular
      approaches to cellular mechanisms involved in the response of "toxic stress" has
      broaden the field of toxicology. Indeed, the development of biological markers
      capable of detecting exposure to toxicants before a full-blown toxic response is
      an important current focus of environmental research. Cells from various
      organisms respond rapidly to toxic stress by altering their metabolic rates, cell
      growth or gene transcription controlling basic functions. Examples included are
      oxidative stress conveyed by peroxisomes, stress proteins implicated in protein
      folding and in detoxification and/or resistance. A number of potential practical
      applications of the stress response and stress proteins can be envisioned. Stress
      gene expression may be considered as a potential "biomonitor" to assess whether
      cells or organisms are experiencing metabolic stress within their environment.
      Such biological indicators should provide an early, sensitive, readily and
      measurable response for monitoring the actions of pollutants. In addition, the
      development of molecular and cellular probes may lead to new classification
      schemes for toxic compounds based upon various cellular and molecular responses
      rather than on toxicant structure.

PMID- 7736256
TI  - [Free radicals and respiratory pathology].
AB  - The lung is particularly exposed to various inhaled toxic products whose toxicity
      can be at least partly mediated by the generation of free radicals. Oxidants
      burden can also result from lung metabolism of xenobiotics or from activation of
      phagocytes. Free radicals are mainly derived from an univalent sequential
      reduction of molecular oxygen. Mitochondria is the main location of intracellular
      production which may also result from auto-oxidation of small molecules or
      function of some enzymes. To prevent the deleterious effects of free radicals
      produced by normal metabolism, cells are equipped with an antioxidant system
      composed of enzymes (superoxide dismutase, catalase, glutathione peroxidase) and
      non enzymatic substances such as glutathione, iron chelators, vitamin E and C,
      ceruleoplsamin). Targets of free radicals toxicity are phospholipids by
      initiation of lipid peroxidation, proteins which may be activated or inactivated
      via oxidation of sulfhydryl residues. Another target is DNA with possible strand
      breaks or mutation. Transcription activities can be also altered and it has been
      recently reported that some transcription factors such as NF-kB can be activated
      by oxidants. Under these circumstances free radicals may be considered as second
      messengers. Lung oxygen toxicity has been largely studied. Oxygen-induced lung
      lesions are non specific. It is possible to induce a resistance to 100% O2 by the
      pre-exposure of animals to 85% O2. This tolerance phenomenon is associated with
      an increased lung content in antioxidant substances. The mechanisms of gene
      regulation of antioxidant enzymes are still poorly understood in eukaryotes.
      Overproduction of free radicals in the lung is also involved in various clinical
      settings such as ischemia-reperfusion, exposure to ozone or NO2, acute
      respiratory distress syndrome, drug induced lung toxicity, pathogenesis of COPD,
      asthma, cancer and ageing. The precise role of free radicals among other
      mechanisms of lung injury is still unclear. A better knowledge of free radicals
      mechanisms of toxicity and of antioxidant regulation is needed to develop
      antioxidant therapeutic strategies.

PMID- 7736257
TI  - [Ochratoxin A, ubiquitous mycotoxin contaminating human food].
AB  - Ochratoxin A (OTA) a mycotoxin produced by molds of the Aspergillus and
      Penicillium genera, contaminates animal feeds and human foods. It has been shown
      to induce renal adenomas and hepatocellular carcinomas in rodents. OTA is
      implicated in Balkan endemic nephropathy, a disease followed by a high incidence
      of urinary tract tumours. Concerning the genotoxicity of OTA, we have recently
      shown, using the [32P]-phosphate postlabelling method, that several DNA-adducts
      are formed in four mice organs treated with OTA. Some of the adducts were
      specific of every analyzed tissue. These results, allow us to state that OTA
      metabolism in different from organ to organ. The influence of OTA metabolism on
      its genotoxic effect was studied. Preliminary results have shown the
      possibilities of oxidative pathways in OTA metabolism leading to genotoxic
      compounds. Effects of some vitamins such as retinol (A), ascorbic acid (C) and
      tocopherol (E), which are known to act as superoxide anion scavengers, were
      tested on genotoxicity of OTA. Pretreatment of mice by vit E induced a decrease
      of the DNA-adducts by 80% in kidney, and by 55% in liver. Vit A and vit C
      decreased DNA-adduct levels by 70% in kidney. In liver, DNA adduct level was
      essentially decreased by vit C (90%). Vit A decreased only the level by 25% in
      this organ. The involvement of oxidative metabolism in the genotoxicity of OTA
      led us to investigate the effect of prostaglandin H synthase (PHS) which is known
      to cooxidase xenobiotics. Aspirin and indomethacin which inhibit this enzyme were
      given prior to OTA administration to mice in order to test this metabolic
      pathway. The decrease observed with aspirin was of about 90% and 30% in kidney
      and liver respectively, and of 90% and 80% with indomethacin in kidney and liver.
      These results confirmed that OTA is activated to genotoxic metabolites by
      cooxydation by the prostaglandin synthase route. Human bronchial epithelial cells
      (BEAS-2B) expressing or not human cytochrome P450s (CYP) (1A2, 2A6, 2D6, 2E1 and
      3A4) were incubated with 0.5 microM OTA for 24 h. DNA-adducts were detected in
      all cells. Total DNA-adduct levels ranged from 4 to 85 adducts per 10(9)
      nucleotides. Some adducts were common to all cell types including cells
      expressing only normal phase II enzymes, but no cytochromes P450. Some other DNA
      adducts were only induced by specific CYPs. The highest DNA-adduct level was
      found in cells where CYP 1A2 was expressed. Nevertheless, more different types of
      DNA-adducts were formed in cells expressing CYP 2D6.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7736258
TI  - [Quantitative histo-enzymological study of delta 5-3 beta-hydroxysteroid
      dehydrogenase activity in rat testis during the perinatal period. Relation with
      testicular crisis in the newborn rat].
AB  - The purpose of the present work was to determine if the neonatal testosterone
      surge in the rat (between 0 and 6 h after birth) was coincident with the
      histological and histochemical changes in the neonatal period. The histological
      study shows a decrease in the number of gonocytes and cells in mitosis. These
      observations are in good agreement with the results obtained by other authors.
      The critical period of birth does not reveal histological changes, between 0 and
      6 h. By contrast, the histochemical analysis, based on the quantitative study of
      the delta 5-3 beta-hydroxysteroid deshydrogenase (key enzyme of the testosterone
      biosynthesis) demonstrated a regular enzymatic activity decreasing, from the
      foetal stage of 20.5 days to the birth, following a drastic increasing, from 0 to
      2 h. The enzyme activity decreases gradually until 1 day after birth. The surge
      has been observed also if the foetus is removed by cesarean. These results
      demonstrated that the testicular crisis of the newborn Rat is simultaneous with
      an increased synthesis of testosterone in the testis.

PMID- 7736259
TI  - [Effects of different types of training on torque/angular velocity relationship.
      Experimental study by isokinetic ergometry in high-level basketball players].
AB  - The purpose of this study was to examine the alterations of the Torque/Angular
      Velocity relationship in knee extensor and flexor muscles due to a long-term
      training programme. Thirty five young elite basketball players were tested
      before, after 12 weeks of a common weight-lifting programme (including concentric
      and eccentric actions) and after 24 weeks including only concentric (C-E/C group)
      or concentric and eccentric actions (C-E/C-E group). After 12 weeks, significant
      decrease in torque of knee extensor muscles was observed. In contrast,
      significant increases in torque of knee flexor and shoulder flexor and extensor
      muscles were noted. After 24 weeks, significant increases were noted in torque of
      all muscular groups, for the C-E/C group but not for the C-E/C-E group. It is
      concluded that training including concentric and eccentric actions have not the
      same effect on agonist and antagonist muscular groups. The alternation of the
      contraction mode influences straingthly the strength restoration.

PMID- 7736260
TI  - [Modelling of viscosity equivalent factor in the human muscle during muscular
      shortening].
AB  - The aim of this study was to calculate the theoretical variation of the non
      linear damping factor (B) as a function of the muscle shortening velocity. The
      theoretical variation of the B factor was determined from a muscle model which
      consists of a contractile component in parallel with a viscous damper both in
      series with an elastic component, and by using the characteristic equation of the
      force-velocity curve. In this muscle model, the viscous element modeled the
      inability of the muscle to generate as a big contracting force (while shortening)
      as possible under isometric conditions. The results show that the theoretical
      behaviour of the B factor was dependent on the shortening velocity and on the af
      parameter which varies according to the muscle fibre type composition and affects
      the curvature of the force-velocity curve.

PMID- 7736261
TI  - [Effects of 17 beta-estradiol and growth factors on cell proliferation and c-fos
      gene expression, in vitro, in endometrial cells in normal growth].
AB  - Glandular epithelial cells (GEC) and stromal cells (SC) were isolated from guinea
      pig endometrium and cultured separately. After the cells were made quiescent by
      serum depletion, cell proliferation and c-fos gene expression were investigated.
      Estradiol-17 beta (E2) alone had no effect on cell proliferation or c-fos gene
      expression. Cell proliferation was observed in SC and GEC after stimulation with
      insulin plus EGF and a supplementary effect was obtained when E2 was associated
      with these factors only in GEC. In GEC, insulin plus EGF had no effect on c-fos
      expression but an effect was observed when E2 was associated with these factors
      or with a protein synthesis inhibitor, cycloheximide (Chx) or puromycine. An E2
      effect in the presence of Chx was also observed in SC. These data suggest the
      presence of a labile protein preventing the in vitro estrogenic action in
      endometrial cells.

PMID- 7736262
TI  - Evaluation and management of the difficult airway.
AB  - Even routine airway management requires specific skills that are best acquired in
      a controlled setting, before "trial by fire" in an emergency situation.
      Furthermore, recognition of a potential difficult airway and appropriate
      preparation prior to initiating airway intervention are critical steps in
      avoiding airway catastrophes in the intensive care or emergency setting.
      Familiarity with a difficult airway algorithm and various alternate techniques
      for endotracheal intubation is a mandatory requirement for all practitioners
      involved in airway management, and should be incorporated in critical care
      curricula. Critically ill patients, by nature, are at risk for complications
      during manipulation of the airway, and may have a higher incidence of adverse
      reactions to anesthesia-inducing drugs and muscle relaxants. In general, "less is
      more" in the intensive care unit, and techniques that preserve spontaneous
      ventilation during airway interventions are desirable, particularly in patients
      with anticipated difficult airways. All intubating sites should have a portable
      storage unit for equipment for managing difficult airways readily available.
      Correct ETT placement always should be verified by detection of exhaled CO2, and
      by chest radiography if prolonged intubation is planned.

PMID- 7736263
TI  - Thoracentesis and chest tube drainage.
AB  - Thoracentesis can be used as both a diagnostic and a therapeutic tool. Tube
      thoracostomy can be life saving. Each technique requires familiarity with the
      principles of pulmonary and pleural anatomy and physiology. It is mandatory that
      all pulmonary and critical care practitioners be familiar with the indications,
      benefits, and risks of these interventions to prevent devastating complications.

PMID- 7736264
TI  - Monitoring ventilator function.
AB  - Maintenance of the patient-ventilator system is the primary role of the
      respiratory care practitioner in the intensive care unit. Patient-ventilator
      system checks should include monitoring the patient's response to ventilation,
      evaluating function of the ventilator, maintaining ventilator settings according
      to physician orders, setting appropriate alarms, maintaining the integrity of the
      ventilator circuit and humidifier, and documenting all of the above. The concept
      of ventilator checks should be expanded and thus, the name changed to patient
      ventilator system check to emphasize the importance of evaluating the patient.
      This article reviews the rationale for performing patient-ventilator system
      checks and measurements.

PMID- 7736265
TI  - Monitoring respiratory mechanics.
AB  - Emphasis is on the mechanical properties of the spontaneously breathing patient.
      The occasional reference to mechanically ventilated patients is used to clarify
      and provide additional insight to the topic of spontaneously breathing
      individuals. Reference to the basic principles of mechanics are to establish the
      foundation for an integrated description of lung mechanics. Finally, a brief
      review of the "state of the art" respiratory monitoring parameters shown to have
      direct clinical applications.

PMID- 7736266
TI  - Metabolic measurements in the critically ill.
AB  - Measurements of VO2 and VCO2 can be used to calculate REE, which can be used to
      determine the caloric requirements and metabolic state of critically ill
      patients. These measurements are made using the gas exchange method--measuring
      the minute ventilation and the differences between the inspired and expired
      concentrations of oxygen and carbon dioxide. Mechanical ventilation provides a
      challenging environment in which to make these measurements because of elevated
      oxygen concentrations, fluctuating airway pressures, and humidity. Careful
      attention must be paid to details to ensure accurate measurements under these
      conditions.

PMID- 7736267
TI  - Noninvasive oxygen monitoring techniques.
AB  - As this article demonstrates, tremendous progress has been made in the techniques
      of oxygen measurement and monitoring over the past 50 years. From the early
      developments during and after World War II, to the most recent applications of
      solid state and microprocessor technology today, every patient in a critical care
      situation will have several continuous measurements of oxygenation applied
      simultaneously. Information therefore is available readily to alert personnel of
      acute problems and to guide appropriate therapy. The majority of effort to date
      has been placed on measuring oxygenation of arterial or venous blood. The next
      generation of devices will attempt to provide information about living tissue.
      Unlike the devices monitoring arterial or venous oxygen content, no "gold
      standards" exist for tissue oxygenation, so calibration will be difficult, as
      will interpretation of the data provided. The application of these devices
      ultimately may lead to a much better understanding of how disease (and the
      treatment of disease) alters the utilization of oxygen by the tissues.

PMID- 7736268
TI  - Capnography for adults.
AB  - Capnography is the measurement of carbon dioxide (CO2) concentration in a gas
      mixture. This article discusses the clinical applications and limitations of
      capnography and end-tidal CO2 monitoring. In addition, an evaluation of the
      technical aspects insofar as to whether they limit or enhance clinical
      application and the physical principles on which the monitors' functions are
      based.

PMID- 7736269
TI  - Arterial blood gas monitoring.
AB  - Arterial blood gas determinations (ABGs) play an important role in diagnosing
      derangements in acid-base balance, oxygenation, and ventilation. Frequent
      assessment is necessary in the management of critically ill patients. This
      article reviews the technologic evolution of modern blood gas analysis and the
      clinical application of monitoring hydrogen ion content (pH), blood oxygen
      tension (PO2), and carbon dioxide tension (PCO2).

PMID- 7736270
TI  - The role of the fiberscope in the critically ill patient.
AB  - The role of the fiberscope in the management of difficult and failed intubations
      has been well established and the importance of learning this valuable skill has
      been emphasized. Nonetheless, the fiberscope is underutilized in anesthesia and
      critical care practices because of a high rate of intubation failure. The main
      cause of failure is lack of expertise in maneuvering the fiberscope. Other
      technical causes of failure include fogging or clouding of the fiberscope's lens,
      drifting off the midline, and inability to advance the endotracheal tube or
      withdraw the fiberscope after completing intubation. Proper selection of the size
      of the fiberscope in relation to the size of the endotracheal tube, adequate
      lubrication, and careful passage of the fiberscope through the distal opening of
      the tracheal tube (not the Murphy eye) prevent difficulties encountered during
      advancement of the tube or upon withdrawal of the bronchoscope. Patient-related
      causes include inadequate topical anesthesia, which leads to abrupt movement of
      the larynx, laryngeal spasm, coughing, and copious secretions; a large floppy
      epiglottis; and tumor and edema of the upper airway, which also interfere with
      exposure of the larynx. Various approaches for learning and applying fiberoptic
      endoscopy have been instituted. The key to increased success involves initial
      training and practice with an intubation model and tracheobronchial tree. These
      models enable the learner to develop the eye-hand coordination skills needed to
      use the fiberscope properly. The fiberscope is best used in patients after
      learning to perform three simultaneous movements--advancing the fiberscope,
      coordinated rotation of the insertion cord, and bending the tip of the fiberscope
      while traversing the airway. After the technical skills of the fiberscope become
      second nature, the endoscopist can give more attention to patient-related factors
      to improve the success rate of tracheal intubation. Expert use of the fiberscope
      can be a life-saving measure through alleviating major airway complications and
      unnecessary tracheostomies.

PMID- 7736271
TI  - Emergency management of the airway.
AB  - When to intervene and control the airway is the critical decision the physician
      must make. The technical expertise and confidence of each physician determine the
      particular airway modality chosen. The medications used depend on each clinical
      setting and can significantly impact the outcome of airway management. To control
      the airway and breathing and move on to circulation requires a broad knowledge of
      alternative airway management techniques and the challenging task of placing each
      into the appropriate clinical setting.

PMID- 7736272
TI  - Oxygen therapy.
AB  - Understanding the various delivery systems of the most commonly used therapies in
      the critical care setting will help avoid iatrogenic problems and enhance ability
      to deliver effective goal-oriented critical care. Rational use of oxygen is a
      result of understanding the goals, complications, and risks of oxygen therapy.

PMID- 7736273
TI  - Bronchial hygiene therapy.
AB  - Bronchial hygiene therapy is useful and effective in the presence of careful
      patient evaluation, clear definition of therapeutic goals, and application of
      appropriate modalities. This article defines the variable bronchial hygiene
      modalities and discusses their indications, contraindications, and applications.
      Prophylactic and therapeutic bronchial hygiene modalities, diagnostic methods
      associated with bronchial hygiene therapy, inhaled antibiotic therapy, and
      therapist driven protocols are also addressed.

PMID- 7736274
TI  - Bronchoscopic procedures in the intensive care unit.
AB  - Fiberoptic bronchoscopy is a valuable tool in the intensive care unit. The
      procedure may be an integral part of airway management and has diagnostic and
      treatment capabilities. Demonstrated expertise is necessary to perform the
      procedure safely and effectively. This expertise may be particularly important
      when faced with a complex patient who presents with airway management problems or
      significant hemoptysis.

PMID- 7736275
TI  - Electron microscopic study of endogenous peroxidase activity in human liver
      macrophages.
AB  - We evaluated the conditions of fixation for ultrastructurally demonstrating the
      endogenous peroxidase (PO) activity of macrophages in biopsied human liver. The
      application of microwaving and immersion fixation with tannic acid and aldehydes
      allowed excellent visualization of PO activity in the nuclear envelope (NE),
      rough endoplasmic reticulum (rER), and cytoplasmic granules (CG), with good
      preservation of cellular ultrastructures. The macrophages with PO activity showed
      one of the following five patterns of PO localization: positive in both the NE
      and rER but negative in the CG (type 1); negative in both the NE and rER but
      positive in the CG (type 2); negative in the NE but positive in both the rER and
      CG (type 3); positive in all three (type 4); PO negative (type 5). The type 1
      cells resembled typical Kupffer cells, type 2 cells monocytes, and type 3 and 4
      cells the exudate-resident macrophages considered to be a transitional form
      between exudate and resident macrophages. Type 5 cells may also be a transitional
      form between the exudate and resident macrophage, or an end-stage macrophage
      derived from exudate macrophages which have lost their PO activity. Tannic-acid
      aldehyde immersion fixation with microwaving may be a useful method in the study
      of the PO activities of macrophages in biopsied human liver specimens.

PMID- 7736276
TI  - Detection of primary and mature transcripts of calcitonin-gene-related peptide
      genes in rat parafollicular cells by light, fluorescence and confocal microscopy.
AB  - Alternative splicing of primary transcripts from the calcitonin/alpha calcitonin
      gene-related peptide (alpha CGRP) gene result in mature mRNAs encoding either
      calcitonin or alpha CGRP. We have produced sequence-specific, synthetic,
      biotinylated oligodeoxynucleotide probes that recognize calcitonin (exon 4), and
      alpha CGRP (exon 6) sequences as well as sequences common to both splice variants
      (exon 3) of this gene. Probes to exons 4 and 3 revealed strong cytoplasmic
      signals in rat parafollicular cells. In addition, a punctate nuclear signal was
      obtained with these probes. The alpha CGRP-specific (exon 6) probe resulted in
      weak cytoplasmic labelling of parafollicular cells, but produced a punctate
      nuclear labelling similar to that seen with the exon 4 and 3 probes. RNase
      digestion removed all the cytoplasmic and nuclear signals obtained with all
      probes. Hybridization with a thyroglobulin-specific probe failed to label
      parafollicular cells. A control (human enterovirus) probe yielded negative
      results, while a probe to rat somatostatin produced cytoplasmic labelling of a
      small subpopulation of parafollicular cells. Finally, a probe specific for beta
      CGRP mRNA labelled most, if not all, parafollicular cells. Fluorescent alkaline
      phosphatase development of in situ hybridizations could be combined with indirect
      immunofluorescence for CGRP. Analysis by fluorescence and confocal microscopy
      revealed that CGRP immunoreactive cells contained calcitonin, alpha CGRP and beta
      CGRP hybridization signals. Our results demonstrate that all three genes may be
      simultaneously expressed by thyroid parafollicular cells and show that synthetic
      biotinylated oligonucleotide probes can be used for highly precise localizations
      of primary transcripts in the nuclei of these cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7736277
TI  - Immunohistochemical localization of cytochrome P450 3A in human pulmonary
      carcinomas and normal bronchial tissue.
AB  - The cytochrome P450 (CYP) enzymes metabolize drugs and other xenobiotics in liver
      and also in some extrahepatic tissues. We have studied the expression and
      localization of CYP3A in primary lung tumours and normal lung tissue from the
      same patients. Thirty-two patients undergoing partial or total lung resection for
      therapy of primary pulmonary carcinoma were included in this study.
      Immunohistochemical staining for CYP3A was performed with a modification of the
      ABC technique. Eight of the 32 cases of primary pulmonary carcinoma showed
      expression of CYP3A. In 12 of the 32 cases of normal tissue, the seromucous
      glands were positive for CYP3A. The bronchial epithelium was positive for CYP3A
      in 11 cases. We observed no correlation between CYP3A expression in tumour tissue
      and that in seromucous glands or bronchial epithelium. We conclude that CYP3A is
      present in both normal and cancerous lung tissue. Our findings suggest, however,
      no co-expression of CYP3A in lung cancer.

PMID- 7736278
TI  - Cholestasis-induced alterations of the trans- and paracellular pathways in rat
      hepatocytes.
AB  - Bile secretion depends on the vectorial transport of solutes from blood to bile
      and involves three different pathways: transcellular pathways mediated by
      transport proteins distributed asymmetrically in the basolateral and canalicular
      plasma membrane and by transcytotic vesicles, and a paracellular pathway allowing
      selective diffusion through tight junctions. All three pathways are impaired
      differentially by extrahepatic (bile duct ligation) or intrahepatic
      (ethinyloestradiol) cholestasis. Ethinyloestradiol treatment leads to tight
      junctional defects that are less severe than those induced by bile duct ligation.
      Junctional impairment is reflected functionally in increased permeability for
      horseradish peroxidase and structurally by decreased strand numbers and increased
      junctional length, but not by alterations at the level of the individual strands.
      The parallelism of physiological and morphological perturbations indicates a
      structure-function relationship in hepatocellular tight junctions. In addition,
      impaired functional integrity of tight junctions following bile duct ligation is
      reflected in a partial loss of hepatocellular surface polarity owing to
      redistribution of some, but not all, domain-specific plasma membrane antigens,
      which might mimic the behaviour of transport systems. After ethinyloestradiol
      treatment no alterations of surface polarity were observed. Thus,
      immunohistochemistry supports the view that ethinyloestradiol results in less
      severe impairment of the tight junctions than bile duct ligation. Finally, bile
      duct ligation, but not ethinyloestradiol, affects the transcytotic vesicular
      pathway; severe impairment of this is reflected in the absence of a late
      horseradish peroxidase peak in bile and also in the accumulation of
      pericanalicular vesicles that are immunopositive for canalicular membrane
      proteins and accessible for bulk phase endocytic markers.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7736279
TI  - Tissue and subcellular distribution of glucokinase in rat liver and their changes
      during fasting-refeeding.
AB  - The distribution of glucokinase in rat liver under both normal feeding and
      fasting-refeeding conditions was investigated immunohistochemically. Under normal
      feeding conditions, glucokinase immunoreactivity was observed in both nuclei and
      cytoplasm of parenchymal cells. The nuclei were stained intensely and evenly,
      whereas the cytoplasm showed weak immunoreactivity of different degrees of
      staining intensity depending on the location of the cells. The cytoplasm of
      perivenous hepatocytes was stained more intensely, though not so much more, than
      that of periportal hepatocytes. The cytoplasm of hepatocytes surrounding the
      terminal hepatic venule (THV), of hepatocytes surrounding the portal triad, and
      of some other hepatocytes showed a stronger immunoreactivity than that of
      residual hepatocytes. The nuclear immunoreactivity in hepatocytes surrounding the
      portal triad and in some other hepatocytes was weak or absent, and positive
      immunoreactivity was detected at the plasma membrane of some of these cells.
      After 72 h of fasting, glucokinase immunoreactivity was markedly decreased in all
      hepatocytes. After the start of refeeding, the cytoplasmic immunoreactivity began
      to increase first in the parenchymal cells surrounding the THV and extended to
      those in the intermediate zone followed by those in the periportal zone. In
      contrast, the increase in nuclear immunoreactivity started in hepatocytes
      situated in the intermediate zone adjacent to the perivenous zone and then
      extended to those in the perivenous zone followed by those in the periportal
      zone. Hepatocytes surrounding either THV or portal triad showed a distinctive
      change in immunoreactivity during the refeeding period. After 10 h of refeeding,
      strong immunoreactivity was observed in both the cytoplasm and the nuclei of all
      hepatocytes, and appreciable glucokinase immunoreactivity was detected at the
      plasma membrane of some hepatocytes. These findings are discussed from the
      standpoint of a functional role of glucokinase in hepatic glucose metabolism.

PMID- 7736280
TI  - Different localizations of 21 and 27 kDa gap-junction proteins in rat salivary
      glands.
AB  - Antibodies against 21 and 27 kDa gap-junction proteins from rat liver were used
      to examine the identification and localization of gap-junction proteins in rat
      salivary glands. Acinar cells of the submandibular glands and parotid glands
      stained well for the 27 kDa gap junction protein and less intensely for the 21
      kDa protein. Acinar cells of the sublingual glands were stained heavily for the
      27 kDa gap junction protein and stained well for 21 kDa gap junction protein. No
      27 kDa protein was observed in the ducts of the salivary glands. The 21 kDa gap
      junction protein was distributed in some of the intercalated ducts in the parotid
      and submandibular glands. Immunoblotting of an extract of parotid glands with
      antibodies against 21 and 27 kDa gap-junction proteins revealed the presence of
      21 and 27 kDa proteins in the parotid glands. It is concluded that the 27 kDa gap
      junction protein is distributed as a major component of the gap junctions in the
      acinar cells of all the salivary glands; the 21 kDa protein is localized as a
      minor component in the acinar cells and some portions of the intercalated ducts
      in the salivary glands. It is possible that these gap-junction proteins might
      contribute to the regulation of function of the salivary glands.

PMID- 7736281
TI  - Immunohistochemical analysis of muscle cytochrome c oxidase deficiency in
      children.
AB  - Despite the demonstration of a clear biochemical defect, the genetic alterations
      causing childhood forms of cytochrome c oxidase (COX) deficiency remain unknown.
      The double genetic origin (nuclear and mitochondrial DNA), and the complexity of
      COX enzyme structure and regulation, indicate the need for genetic investigations
      of the molecular structure of individual COX subunits. In the present study a new
      monoclonal antibody, which reacts exclusively with heart-type human COX subunit
      VIIa (VIIa-H), and other monoclonal antibodies against human COX subunits, were
      used in the immunohistochemical analysis of skeletal muscle from children with
      different forms of mitochondrial myopathy with COX deficiency. By
      immunohistochemical investigation a normal reaction was seen with antibodies to
      COX subunits IV, Va+Vb, and VIa+VIc in all four cases, and in two cases with
      antibodies to COX VIIa-H and VIIa+VIIb. In muscle from a fatal infantile case
      with cardiac and skeletal muscle involvement, no immunohistochemical reaction was
      seen with the monoclonal antibody against the tissue-specific subunit VIIa-H. In
      muscle from an 11-year-old boy with exclusive muscular symptoms and signs,
      immunohistological reactions were absent with COX subunit VIIa-H and COX subunits
      VIIa+VIIb, and slightly decreased with COX subunit II, thus demonstrating a
      different molecular mechanism in each case. It is concluded that the molecular
      basis of COX deficiency in childhood may vary greatly between patients.

PMID- 7736282
TI  - Immunocytochemical localization of glycogen phosphorylase in primary sensory
      ganglia of the peripheral nervous system of the rat.
AB  - Neuronal localization was investigated of glycogen phosphorylase (GP) in ganglia
      of the peripheral nervous system of the rat. Immunofluorescence and
      immunoenzymatic procedures were applied with a monoclonal anti-bovine brain GP
      antibody on paraformaldehyde-fixed, paraffin-embedded tissues. Immunoreactivity
      was only present in the somatic neurons of the mesencephalic trigeminal nucleus
      in the brain stem and in dorsal root ganglia (DRG), but not in the autonomic
      neurons of the superior cervical ganglia or in the sensory nuclei of the spinal
      cord. GP immunoreactivity was present as early as day 1 after birth. In the adult
      rat, staining was present in neurons of different sizes, and to varying
      intensities. No relationship was apparent between the staining intensities and
      morphologically distinguishable types of neurons. In DRG, the type of reactivity
      was the same from cervical to sacral ganglia. The selected occurrence of GP in
      specific neurons of the peripheral nervous system in contrast to the ubiquitous
      occurrence in all astrocytes of the central nervous system may indicate a
      different role of neuronal glycogen compared to astrocytic glycogen.

PMID- 7736283
TI  - Immunolocalization of soluble guanylyl cyclase subunits in rat kidney.
AB  - Stimulation of soluble guanylyl cyclase (SGC) by nitric oxide (NO) results in the
      generation of cyclic guanosine monophosphate (cGMP). We recently described
      expression of abundant nitric oxide synthase, the enzyme by which NO is generated
      from L-arginine in macula densa cells of rat kidney at the protein and mRNA
      level. In the present study we looked for possible targets of NO in the kidney.
      By light and electron microscopy, we applied polyclonal antisera against four
      subunits (alpha 1, alpha 2, beta 1, beta 2) of SGC in immunocytochemical studies
      of frozen sections of rat kidney. We demonstrate the presence of alpha 1-subunit
      in glomerular podocytes and of beta 2-subunit in principal cells of the
      collecting duct. In both cell types a cytosolic localization was evident from
      ultrastructural analysis. Regarding the collecting duct, NO was shown by other
      authors to inhibit sodium reabsorption in cultured mouse cortical collecting duct
      principal cells. In podocytes NO may relax the contractile system of podocyte
      food processes, the tone of which has been suggested to counteract the elastic
      distension of the capillary wall.

PMID- 7736284
TI  - Recent advances in the doubly labeled water technique. Proceedings of a workshop
      meeting held at the 78th annual FASEB meeting in Anaheim, CA (April 1994).

PMID- 7736285
TI  - Analytic requirements for the doubly labeled water method.
AB  - The doubly labeled water method is the first method that accurately measures
      total daily energy expenditure in free-living subjects over periods of days to
      weeks. Validations have indicated that the method can be performed with a
      coefficient of variation of between 3% and 5%. This precision, however, is
      dependent on the quality of the isotopic analyses. A recent interlaboratory
      comparison has indicated that there is a wide variation in the accuracy and
      precision with which deuterium and 18O enrichments are measured. This reduces the
      accuracy and precision with which a laboratory will perform the doubly labeled
      water method and in some cases may limit the application of this technique.
      Herein we review the analytical requirements for optimal use of the method and
      some of the potential sources of error in the stable isotope analysis.

PMID- 7736286
TI  - Impact of 2H and 18O pool size determinations on the calculation of total energy
      expenditure.
AB  - Measurement of total energy expenditure using [2H,18O] water requires both
      accurate and precise determination of the rates of disappearance of 2H and 18O
      from body water over time and determination of the 2H and 18O pool sizes.
      However, the impact of the isotopic determination of body water upon the
      determination of energy expenditure is often overlooked. For measurement of total
      body water per se, the delay after administration before sampling body fluids
      becomes important, and saliva sampling can be used to resolve the timing of early
      samples for body water determination. For energy expenditure measurement per se,
      linear regression can be used to define the initial dilution. Because the
      hydrogen tracer dilutes into a pool significantly larger than body water pool per
      se due to the presence of labile hydrogens, a correction to the isotope pool size
      must be applied. The theoretical calculations of the exchangeable hydrogen pool
      presented here suggest that the hydrogen pool size is < 3% greater than the body
      water pool and data are provided to support this idea. Finally, the two
      approaches used to define the body water pool space contribution to the
      calculation of energy expenditure using 2H2(18)O are reviewed. Using a pool size
      based upon the average of the two pool spaces limits the effect of pool size
      error in the calculation of energy expenditure.

PMID- 7736287
TI  - Multiple laboratory comparison of the doubly labeled water technique.
AB  - A double-blind study was conducted to determine between-laboratory variability in
      the doubly labeled water method for measurement of total energy expenditure in
      humans, and to compare the accuracy and precision of three widely-used procedures
      for calculating rates of carbon dioxide production from the original isotope
      data. Eighteen laboratories from five countries participated in the study. All
      laboratories were provided with five water standards containing varying amounts
      of 2H and 18O, and in addition 11 laboratories were provided with urine and dose
      specimens from one (six laboratories) or two (five laboratories) healthy elderly
      subjects of normal height and weight undergoing a calorimetric validation of the
      doubly labeled water method. The data from the five water standards were analyzed
      to predict between-laboratory variability in the doubly labeled water technique
      in all laboratories. In addition, data from the subjects were analyzed using the
      "slope-intercept", "2-point" and "modified" methods of calculation. The results
      confirm that the doubly labeled water method can be an accurate technique for the
      measurement of energy expenditure in adult human subjects in some laboratories.
      However, there was substantial between-laboratory variability in the results and
      some laboratories returned physiologically impossible results. There was no
      significant effect of calculation procedure on the accuracy of the technique in
      this limited comparison, although the slope-intercept procedure appeared to be
      more susceptible to analytical error than the other procedures. The isotope
      standards analyzed by participants in this study will be made available to other
      investigators on request.

PMID- 7736288
TI  - Estimation of precision in DLW studies using the two-point methodology.
AB  - Previous attempts to estimate precision of doubly labeled water (DLW) estimates
      of CO2 production, using propagation of error analyses, have necessarily made
      simplifying assumptions which may compromise the resultant error estimate. Using
      an empirical iteration approach, error distributions for the DLW calculation were
      generated which overcome these problems. The error distribution for CO2 estimates
      generated by DLW is symmetrical but not normal. The distribution is significantly
      truncated such that the 99% inclusion limits are 2.034 SD and not 2.58 SD. The
      precision error (99% CI for mean as percent of the mean) in DLW experiments, when
      using duplicate analyses, varies between approximately 3% and 47% depending on
      the ratio of the elimination constants of the two labels (ko/kd), experimental
      duration and initial isotope dose. The error could be improved by approximately
      10 fold by increasing the number of replicates at all six isotope determinations
      from 2 to 5. Estimating precision in actual experiments can be made using the
      same empirical approach. The resultant estimates can be of extreme value in
      evaluating the role of precision as a factor influencing deviations during
      validation studies, and also for weighting mean estimates in applications of the
      technique. The deviations of DLW estimates from those made simultaneously by
      indirect calorimetry in a small mammal validation study were generally greater
      than the precision of the DLW estimates of CO2 production. This may indicate
      there are more problems with the technique than precision alone.

PMID- 7736289
TI  - Correction approaches for doubly labeled water in situations of changing
      background water abundance.
AB  - Doubly labeled water (DLW) is an accurate, portable method for measuring free
      living energy expenditure. However, under certain conditions shifts in baseline
      abundance of deuterium and oxygen-18 tracers used in the method may produce
      errors in derivation of both turnover (k) rates and calculated energy
      expenditure. Present objectives were to examine during what experimental
      situations baseline errors arise and to address means of correcting for such
      baseline shifts so that consequent errors in energy expenditure calculations are
      minimized. Under conditions where shifts in baseline abundance for deuterium and
      oxygen-18 parallel abundances corresponding to the natural meteoric water ratio,
      self-compensating changes in k values for both deuterium and oxygen will result
      in minimal error to the DLW energy expenditure calculations, provided that the
      dose ratio of isotopes also mimics the meteoric water line. However, in
      situations where relative shifts in abundance of each isotope across the
      measurement period are not in parallel relative to the natural meteoric water
      line, then the potential for larger DLW errors exists. Optimally, subjects should
      equilibrate with the new water source. Failing this, correction for shifting
      baseline can be accomplished by measuring isotopic abundance changes in a control
      group of subjects not given the DLW dose, but performing similar tasks and
      consuming the same diet as the group given DLW. Alternatively, theoretically
      based correction values can be calculated given knowledge of the abundances of
      the final drinking water and the interval time that subjects consumed the new
      fluid.

PMID- 7736290
TI  - The Maastricht protocol for the measurement of body composition and energy
      expenditure with labeled water.
AB  - An update of practical aspects of the use of labeled water for the measurement of
      total body water (TBW) and energy expenditure (EE) is presented as applied in
      Maastricht, The Netherlands. We use a 10-hour equilibration period. The isotopes
      for the measurement of TBW and EE are routinely administered, after collecting a
      background urine sample, as a last consumption before the night. Our data show an
      underestimate of TBW measured with isotope dilution after 4 hours (in the
      morning), a discrepancy which increases with the size of TBW. No such relation
      and no significant differences were found after 10-hour (overnight)
      equilibration. The ratio between the dilution space for deuterium and oxygen-18
      is higher than the earlier figure of 1.03, especially in adult subjects with a
      high body fat content. For an observation period of EE over two weeks, samples
      from the second and the last voiding on the first, mid, and last day of the
      observation period are collected. Differences in EE calculated from morning and
      evening samples within the first and second week allow detection of sampling
      errors and if so, samples are excluded from the final calculation. Differences of
      EE between weeks 1 and 2 allow a check for the consistency of the subjects'
      physical activity level and usually fall within 10% of the average EE over the
      total observation interval.

PMID- 7736291
TI  - Variation in total energy expenditure in humans.
AB  - The purpose of this paper is to review current data regarding the factors
      contributing to variability in total energy expenditure (TEE) among humans.
      Variation arising from within and between individuals and between study groups
      will be considered. For within- subject variation, issues relating to
      experimental and theoretical measurement error will be considered in addition to
      inherent physiological variation. The literature reporting TEE in various study
      groups is reviewed, highlighting deficiencies in current comparison methods, and
      a framework by which TEE can be compared between studies and populations is
      suggested. For between-subject variation, the effects of differences in body
      composition, obesity, age and gender upon variation in TEE are examined. Finally,
      data will be reviewed relating to changes in TEE in response to external
      manipulation (e.g., activity, overfeeding, stress).

PMID- 7736292
TI  - Energy expenditure in lean and obese prepubertal children.
AB  - The relationship between energy expenditure and obesity was examined in
      prepubertal children. Consenting fifth graders underwent Tanner Staging, weight,
      height and skinfold measurements. Subjects were selected for further study to
      obtain equal numbers of girls and boys with a wide range of body composition.
      Weight, total daily energy expenditure (TDEE) by doubly labeled water (DLW),
      resting metabolic rate (RMR), and body composition were measured. Children were
      grouped into level of obesity based on tertiles of subscapular plus triceps
      skinfolds. The skinfold tertiles did quite well in grouping subjects by degree of
      obesity, as differences in percent fat in each tertile were significantly
      different. There were no differences in fat-free mass between the groups, while
      the highest tertile group weighed 14 kg more than the lowest. For DLW, energy
      expenditure was calculated using day 8 and day 9 urine samples as the final time
      point to examine precision. Mean energy expenditure using either day was nearly
      identical (2220 +/- 400 vs 2300 +/- 370 kcal/d), with a CV of the difference of
      5.5%. No differences in RMR, energy expended in activity, or TDEE between the
      three groups were observed. A reduction in RMR or TDEE could not explain
      differences in obesity in these prepubertal children. However, the fact that the
      heaviest children expended the same amount of energy in activity and had the same
      TDEE as the leanest, while weighing 14 kg more, indicates that the obese children
      had a reduced activity level.

PMID- 7736293
TI  - A new sample preparation method for isotope ratio mass spectrometry of 2H
      enriched samples generated by the doubly labeled water method.

PMID- 7736294
TI  - Research utilization: reconnecting research and practice.
AB  - Barriers to the use of research in practice include problems with the
      availability of research, the manner in which it is presented, and the use of the
      research. They also include barriers in the setting and "shortcomings" of
      individual nurses. Most approaches to increasing research utilization have
      focused on the "shortcomings" of clinicians. A more useful approach is to make
      changes in both education and practice to rejoin researchers and clinicians and
      to reconnect the conduct and use of research.

PMID- 7736295
TI  - Evaluating cerebral oxygenation using jugular venous oximetry in head injuries.
AB  - When caring for the critically ill patient, a primary objective is to maintain an
      adequate delivery of oxygen to the tissues. Monitoring and ensuring satisfactory
      cerebral oxygen delivery in patients at risk for cerebral ischemia presents a
      significant challenge to the clinician. Cerebral oxygen content usually is
      determined using blood gas analysis, whereas blood flow to cerebral tissues is
      inferred from monitoring of the cerebral perfusion pressure. There is an
      assumption that cerebral oxygen delivery is adequate so long as the cerebral
      perfusion pressure exceeds 50-60 mmHg in the normal brain and the cerebral
      arterial oxygen content is normal. The cerebral perfusion pressure, however, is
      an estimated value calculated as the difference between the mean systemic
      arterial pressure and the intracranial pressure and provides merely an indirect
      index of the adequacy of cerebral oxygen delivery. The validity of the cerebral
      perfusion pressure as an index for cerebral oxygen delivery becomes questionable
      when the autoregulatory mechanisms of the brain are disturbed, as in severe head
      injuries. Jugular bulb oxygen monitoring provides a method of evaluating cerebral
      oxygenation status for early identification of impending ischemia by measuring
      oxygenation of the mixed cerebral venous blood. In this article, the authors
      review the physiology of cerebral oxygenation, describe a method of monitoring
      cerebral oxygenation using jugular bulb oximetry, and review a case study to show
      how these assessments can affect the nursing care of the head-injured patient.

PMID- 7736296
TI  - High-risk unstable angina: keeping pace with current research findings.
AB  - Unstable angina pectoris is one of the leading medical diagnoses of patients
      admitted to hospitals in the United States and may advance to acute myocardial
      infarction, morbidity, and death in many instances. Research into the
      pathophysiology of unstable angina has led to new management regimes, including
      medications, interventions, and invasive treatments. In this article, the author
      describes unstable angina and its pathogenesis, then focuses on pharmacologic and
      invasive management. Primary nursing diagnoses are described, and special
      considerations are discussed to help critical care and/or advanced practice nurse
      assess patient needs, monitor therapies, optimize care, and mediate patient
      stress.

PMID- 7736297
TI  - Strategies to optimize the cardiorespiratory status of the critically ill.
AB  - The goal of cardiorespiratory monitoring is to evaluate the components of oxygen
      delivery and consumption. Parameters obtained from the physiologic profile are
      used to assess and optimize oxygen transport to meet the tissue needs of the
      critically ill patient. Threats to the process of tissue oxygen balance can lead
      to inadequate utilization at the cellular level. Therapeutic interventions can be
      implemented to optimize the cardiorespiratory status of the critically ill
      patient. Intervention strategies are not directed at simply achieving normal
      values or even supranormal values but at identifying the relation of oxygen
      delivery to oxygen consumption to potentially eliminate the development of oxygen
      debt.

PMID- 7736298
TI  - Propofol: a new treatment in intensive care unit sedation.
AB  - Intubated, mechanically ventilated adult patients often require continuous
      sedation to alleviate anxiety and stress. Treatment decisions must balance the
      appropriateness and results of therapy with cost/benefit analysis. Propofol is a
      new drug to the intensive care setting; previously, it was used as an anesthetic
      sedative in the operating room. Many staff nurses are not familiar with the use
      of propofol in intensive care. In this article, the author reviews current
      practical uses and benefits for patients.

PMID- 7736299
TI  - Combined kidney and pancreas transplantation.
AB  - Diabetes is the leading cause of end-stage renal disease in the United States.
      Combined kidney and pancreas transplantation is a safe and effective treatment
      option for diabetic nephropathy. During the past decade, pancreas transplants had
      improved outcomes as a result of improvements in pancreas recovery and
      preservation, the surgical procedure, immunosuppressive regimens, and immunologic
      monitoring. Current 1-year patient and graft survival rates are 90% and 80%,
      respectively, and evidence is accumulating that improvements occur in
      microvascular and neuropathic complications as well. Successful outcomes of
      kidney and pancreas transplantation are due in large part to careful nursing
      assessment, diagnosis, intervention, teaching, and discharge planning.

PMID- 7736300
TI  - Redefining nursing according to patients' and families' needs: an evolving
      concept. AACN Certification Corporation.
AB  - Patients' and families' needs have been displaced from the core of today's health
      care system. Nurses are positioned to serve a pivotal role during such a critical
      time, as health-care systems evolve. The health-care system of the future must be
      driven by the needs of patients and families. Nurses must make decisions and take
      actions that are crucial in ensuring that this becomes a reality. Nurses must
      acknowledge that the historical conceptualization of nursing--delineating
      clinical practice dimensions according to a patient's diagnosis, a nurse's role,
      the clinical setting, and the patient's psychosocial and physiologic systems--is
      of limited value if we are to meet these future challenges. Redefining nursing
      practice according to patients' needs provides an organizing framework to
      examine, across all levels of nursing, the dimensions of practice most likely to
      meet patient needs and contribute to optimal outcomes, as well as enhance the
      linkages between practice, education, and research.

PMID- 7736301
TI  - Comparison of peripheral temperature measurements with core temperature.
AB  - The authors' objective of this study was to identify a peripheral method of
      measuring body temperature that approximates core body temperature. A cross
      sectional design was used to compare peripheral measures of body temperature with
      core temperature. Peripheral temperatures were measured in the ear using two
      infrared thermometers, in the mouth using a mercury in glass thermometer,
      electronic thermometer, and chemical indicator thermometer, in the axilla using a
      mercury in glass thermometer, electronic thermometer, and chemical indicator
      thermometer, and in the rectum using a mercury in glass thermometer and
      electronic thermometer. A statistically significant difference was found between
      peripheral temperature measures and core temperature, except for the axillary
      chemical indicator temperature and both aural temperatures. Pearson correlation
      coefficients of > or = 0.79 were found for the association of pulmonary artery
      temperatures with oral mercury, oral electronic, axillary electronic, rectal
      mercury, and rectal electronic temperatures. Correlation coefficients were less
      than 0.20 between pulmonary artery and aural temperatures measured by both
      devices. Based on results from this study, there is no perfect instrument for
      approximating core temperature, although the electronic thermometer used orally
      has a low mean difference (0.18 degree C), low standard deviation of the
      difference (0.24 degree C), and a correlation coefficient of 0.79.

PMID- 7736302
TI  - Update on implantable cardioverter defibrillators: knowing the differences in
      devices and their impact on patient care.
AB  - Sudden cardiac death, a common cause of cardiac mortality, can be treated with
      either pharmacologic therapy or implantation of an implantable cardioverter
      defibrillator. Tremendous technologic advances have changed implantable
      cardioverter defibrillator therapy from shock-only therapy to multiprogrammable,
      tiered-therapy devices with backup pacing. Methods of implantation have changed
      from open chest to non-thoracotomy procedures. To provide optimal patient care,
      the critical care nurse is challenged to be knowledgeable about the different
      devices. In this article, the authors examine the commonalities and differences
      in device function in the seven currently available implantable cardioverter
      defibrillators and their impact on patient care.

PMID- 7736303
TI  - Professional issues, technical innovations, and clinical trends. Selected
      proceedings from the 9th annual Mellen Conference on Acute and Critical Care
      Nursing. Cleveland, Ohio, September 1994.

PMID- 7736304
TI  - When do we say when? Reflections and reexamination of nursing's response to
      addictive behaviors.

PMID- 7736305
TI  - Brief intervention as an advanced practice strategy for seriously injured victims
      of multiple trauma.
AB  - Trauma is the leading cause of death during the first 4 decades of life.
      Approximately 40-50% of seriously injured patients who require hospitalization
      have an alcohol-related injury. The traumatic injury offers nurses in advanced
      practice roles a unique opportunity to discuss the relation between the patients'
      traumatic injuries and their alcohol use. One strategy that has shown promise in
      recent research is the Brief Intervention, a simple and quick clinical tool used
      to motivate patients to consider the consequences of their alcohol-related
      behavior. The Brief Intervention technique uses a screening instrument, the
      Alcohol Use Disorders Test, to determine whether the patient is a sensible,
      heavy, or dependent drinker. A counseling session, focusing on reducing alcohol
      use in the nondependent drinker, follows while the patient is still acutely
      injured. Through the use of Brief Intervention, the nurse has an opportunity to
      motivate trauma patients to change their patterns of drinking and limit their
      risk for repeated injuries. If nurses can prevent future injuries, the potential
      savings in lives lost and dollars spent are huge.

PMID- 7736306
TI  - Nursing care of domestic violence victims in acute and critical care settings.
AB  - Nursing care of domestic violence victims has focused on emergency settings,
      primary health-care settings, and mental health-care settings. Nurses in other
      acute and critical care settings also care for domestic violence victims, though
      the focus of nursing care may be confined to the medical reason for the person's
      hospital stay. However, as we come to fully appreciate the psychobiologic nature
      of health, illness, and healing, it becomes clear that abuse and violence in a
      patient's home life holds consequences for one's current and future well-being.
      Though hospital stays are often brief, important groundwork can be accomplished
      to identify and assist patients involved in abusive relationships.

PMID- 7736307
TI  - Perinatal substance use: promoting abstinence in acute care settings.
AB  - All health-care providers need to understand the effects of alcohol, nicotine,
      and other drugs on the mother and developing fetus and the ways to promote
      abstinence or at least a decrease in use. The use of these substances may produce
      chronic and/or catastrophic effects that force the pregnant woman into contact
      with the health-care system. Such contact can produce a healthier outcome for
      both the mother and fetus if it includes identification of substance use and
      intervention to promote abstinence. In this article, the author describes the
      consequences of prenatal substance use for the mother and fetus, identifies
      techniques used to screen and assess prenatal substance use, and explains
      strategies used to intervene in prenatal substance use.

PMID- 7736308
TI  - Outcomes: two directions--research and management.
AB  - Outcomes research took hold in the late 1980s. Because of the rising costs of
      health care, policymakers demanded an objective analysis of treatments and
      interventions as demonstrated by cost-effective patient outcomes. More recently,
      outcomes management programs have surfaced. In contrast to outcomes research,
      which is concerned with effectiveness, outcomes management is concerned with
      efficiency. Therefore, this one concept, outcomes, has moved in two related but
      different directions. Understanding outcomes from both the research and
      management perspectives is a challenge facing the nursing profession.

PMID- 7736309
TI  - Clinical guidelines: fad, fact, or vision.
AB  - Interest in clinical guidelines is expanding significantly. Clinical guidelines
      have been developed by the Agency for Health Care Policy and Research, specialty
      organizations representing almost every health-care discipline, and individual
      agencies and facilities. Clinical guidelines may be used in the development of
      practice and patient care standards and within care delivery models such as case
      management. Clinical guidelines offer professional nurses an opportunity to
      define their practice and their contributions to outcomes-based patient care.
      Clinical guidelines also may enable interdisciplinary continuous quality
      improvement to ensure ongoing optimization of care delivery and patient outcome.
      Therefore, clinical guidelines can be used to design patient care that is truly
      driven by patient need and that empowers optimal contributions by nurses and all
      other members of the caregiving team.

PMID- 7736310
TI  - Advanced nursing practice: legal concerns.
AB  - Empowerment of nurses in advanced nursing practice begins with an understanding
      of the current legal status of the advanced nurse practitioner. True empowerment
      will not occur until the reform regulations needed to expand the role of the
      advanced nurse practitioner is understood by nurses and measures are taken to
      begin such reform. In this article, the author reviews the current legal status
      of advanced nurse practitioners, while projecting the needed reforms that must
      occur across the country. The aim is to help advanced nurse practitioners
      undertake measures to ensure that legal empowerment for themselves becomes a
      reality.

PMID- 7736311
TI  - [30 years' development of economic theories in confrontation with facts].
AB  - In 1969, R. Frish and J. Tinbergen received the first Nobel Price in Economics.
      200 years after Quesnay's "economic tables", economics were at last considered as
      a science. During the last thirty years, economics haven't lost their scientific
      reputation, but, confronted with different situations in the world and in France,
      economics have been unable to bring appropriate solutions to every problem.
      Nowadays, economics are quite far from the promises born after the Second World
      War: indeed, until the 1974 world crisis, Keynes' theory (from a macro-economic
      point of view) and Walras' formalisation of the markets (from a micro-economic
      point of view) were sufficient to give satisfying representations of any economic
      reality and mechanism. Nevertheless, these theories were unable to deal with both
      growing unemployment and raising inflation in the late 70's and early 80's.
      Today, economics present a wide variety of efficient analysis of society. Game
      theory, behaviour theory or econometrics are new means used to found new kinds of
      reality representation. Therefore, if economics can no longer be considered as an
      exact science, it remains nevertheless scientific.

PMID- 7736312
TI  - [Geographic inequity revisited: medical staffing of the French territory (1964
      1994)].
AB  - In 1964, a study evidenced the lack of geographic mobility among French doctors:
      young graduates are reluctant to take an installation far away from the city of
      their medical school. Since a law in 1971 entrusted the government with fixing
      the numerous clausus of each medical school--all medical schools are state-run in
      France--this paved the way for correcting inequalities in medical staffing by a
      differenciated student intake according to regions. A study conducted in 1974
      quantified this action region by region. Two decades later, one can observe that
      such an action was not undertaken extensively. However, in relative terms, there
      was some reduction of geographic inequity in medical staffing. As a matter of
      fact, the steady growth of French medical workforce and change in all the health
      system have modified drastically the perceived topic.

PMID- 7736313
TI  - [30 years in the history of drugs and drug therapy].
AB  - The last three decades have been undoubtedly a "revolutionary time" in the life
      of pharmaceuticals. Progress in scientific knowledge and medical practice have
      fueled tremendous change in the drug universe. The "drug chain" has been totally
      transformed, from the early conception through evaluation by the public
      authorities to end up with the utilization by the patient. The article describes
      all these transformations in the French context.

PMID- 7736314
TI  - [French demography in the last 30 years].
AB  - From 1964 to 1994, French population has gained nearly 10 million, up to 57.8
      million. Infant mortality, adult mortality, fertility, nuptiality, immigration
      from abroad and internal migration have undergone drastic change. Noteworthy is
      the rising life expectancy at birth and, more importantly, the growing life
      expectancy of the elderly. French population is aging. The "under 20" who were
      33.7 percent in 1964 are today only 26.4 percent.

PMID- 7736315
TI  - [Medical informatics: historical roots and development since the 60's].
AB  - From the start, the development of the industrialized countries required
      observations in order to get informations on the demographic, administrative and
      health situation. In the course of centuries, methods of collecting and
      evaluating data improved. On the other hand, there was a stepwise development of
      auxiliary technical devices which allow to keep proven components and compose
      them with new ones under higher angles. Individual pioneers contributed to
      develop computers of high calculating capacity. The semi-conductor technique, its
      ongoing improvement and use in microelectronic industry gave rise to a revolution
      of information engineering. There was a tremendous development since the early
      sixties with an expanded use of computers in medicine. In a first phase, they
      helped overtaking auxiliary functions in clinical administration and measuring
      equipment in laboratories. Then, patient oriented systems with large data bases
      were created. In recent years, electronic telecommunication connecting hospital
      information systems (e.g. in university hospitals), but also other information
      centres on a national and international level, is of growing importance. The
      development of information techniques with broadened fields of application--e.g.
      medical image processing, handling of linguistic problems--is a challenge for
      medicine. Medical thinking has to channel information techniques properly with
      the aim of getting useful results, conserving privacy and avoiding irrelevant
      decision making.

PMID- 7736316
TI  - Serum intact parathyroid hormone in a random population sample of men and women:
      relationship to anthropometry, life-style factors, blood pressure, and vitamin D.
AB  - Intact parathyroid hormone (PTH) in serum was determined in a random population
      sample and was related to age, sex, body composition, life-style factors, blood
      pressure, blood lipids, plasma fibrinogen, and serum IGF-1, osteocalcin, and
      vitamin D. Within the framework of the WHO MONICA Project in the city of
      Goteborg, Sweden, 181 men and 166 women aged 25-64 years were studied. Intact PTH
      concentrations varied with age but were similar in both sexes (range 4-82
      ng/liter) [mean (+/- SD) 23.8 +/- 10.4 ng/liter in men and 25.1 +/- 10.6 ng/liter
      in women]. Intact PTH concentrations increased with increasing age, body mass
      index, systolic blood pressure, and 1,25(OH)2D3 and decreased with increasing
      25(OH)D3 in all subjects. Additionally, in men, intact PTH correlated positively
      to diastolic blood pressure and negatively to coffee consumption. In women, PTH
      also correlated negatively to smoking and IGF-1. In a multivariate analysis
      including all variables, age lost its significance. In both sexes there were
      independent positive relations between intact PTH and body mass index and
      1,25(OH)2D3, and negative relations between PTH and smoking habits as well as
      25(OH)D3; among men there was also negative relations between PTH and coffee
      consumption. The results indicate that life-style factors such as smoking and
      coffee consumption decrease the serum concentration of intact PTH, and the same
      effect is seen in individuals with low body mass index. Coffee intake, smoking,
      and low body mass index are also known to adversely affect bone mineral content,
      highlighting the relationship between PTH and bone metabolism.

PMID- 7736317
TI  - Acute effects of deflazacort and prednisone on rates of mineralization and bone
      formation.
AB  - The aims of this study were to determine (1) whether acute suppression of bone
      formation could be evaluated after the administration of corticosteroids in man
      by quantitative bone histomorphometry; and (2) whether there were significant
      differences between the effects of prednisone and its analog deflazacort.
      Thirteen patients who needed high-dose corticosteroid therapy were randomly
      allocated to two groups of treatment (prednisone or deflazacort). Quantitative
      bone histomorphometry, using the technique of triple labeling, and biochemical
      measurements of bone turnover were studied. There were no differences in
      biochemical indices of bone turnover between prednisone and deflazacort at the
      beginning and end of the 15 days of treatment course. During corticosteroid
      treatment, there were no significant changes in biochemical indices of bone
      turnover but a significant decline in total alkaline phosphatase (P < 0.01).
      Histomorphometric indices, as revealed by measurements of tetracycline interval
      and extent of labeling, showed no significant differences in either mineral
      apposition rate or bone formation rate in the two groups. We conclude that the
      acute glucocorticoid suppression of bone turnover by glucocorticoids is not
      detectable within the first 2 weeks of treatment by histomorphometric techniques.
      No differences in bone effects of prednisone and deflazacort were detected in
      this short-term study.

PMID- 7736318
TI  - Calcitriol effect on natural killer cells from hemodialyzed and normal subjects.
AB  - Patients with chronic renal failure have a decreased secretion of calcitriol
      (CTR). They also show an impaired cellular immune response including a defective
      natural killer (NK) cell-mediated activity. The aim of this study was to analyze,
      in vivo and in vitro, the effect of CTR on NK cell cytotoxicity in healthy
      control subjects and in hemodialyzed (HD) patients. Our results show that HD
      patients had baseline-depressed NK cell activity when compared with controls (P <
      0.001), which increased significantly after 1 month of oral CTR treatment (0.5
      microgram/day) (P < 0.001). Calcitriol treatment also induced a significant
      increase in CTR serum levels (P < 0.001) and a significant decrease (P < 0.001)
      in total parathyroid hormone (PTH). In vitro CTR treatment (10(-7) M) of
      peripheral blood mononuclear cells (PBMC) increased NK cell-mediated cytotoxicity
      after 24 hours of incubation with a maximum at 48 hours (P < 0.001). In vitro CTR
      treatment at doses of 10(-11) and 10(-9) M did not significantly increase NK
      cytotoxic activity. The enhanced NK activity after CTR treatment was not the
      consequence of increased numbers of CD56 positive cells, nor to lymphocyte
      activation, as tested by the expression of the interleukin 2 receptor p55 alpha
      chain (CD25) on their surface. In vitro treatment of PBMC from HD patients with
      CTR (10(-7) M, during 48 hours) also induced a strong increase in NK cell
      cytotoxicity (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736319
TI  - An electron probe X-ray microanalytical study of bone mineral in osteogenesis
      imperfecta.
AB  - A semiquantitative electron probe X-ray microanalytical (XRMA) technique, in
      conjunction with transmission electron microscopy, was used to compare the
      calcium to phosphorus (Ca/P) molar ratios in calcium phosphate standards of known
      composition, in normal bone and in bone from patients with osteogenesis
      imperfecta (OI). Using a modified routine processing and resin embedding
      schedule, the measured Ca/P molar ratio of calcium phosphates standards of known
      composition were found to correlate well with the Ca/P molar ratio based on their
      respective chemical formulae. This technique was then used to compare the Ca/P
      molar ratio in normal human bone and in OI bone. The Ca/P ratio values for normal
      bone (Ca/P = 1.631) correlated well with those for chemically prepared
      hydroxyapatite (Ca/P = 1.602), but in bone from OI patients, the Ca/P molar ratio
      was significantly lower (Ca/P = 1.488). This study has shown that there is a
      lower Ca/P molar ratio in OI bone compared with normal, matched bone. This
      suggests that the mineral deviates from the carbanoapatite usually found in bone.
      Isomorphous substitutions in the carbanoapatite lattice could account for this
      although this study has neither proved nor disproved this. The altered bone
      mineral is another factor that could contribute to the increased fracture rate
      observed in OI.

PMID- 7736320
TI  - Bone progenitor cell deficits and the age-associated decline in bone repair
      capacity.
AB  - Aging bone shows a progressive decline in mass and strength. Previous studies
      have suggested that bone marrow stem cells are reduced with aging and that this
      could be responsible, in part, for age-associated bone deficits. We measured the
      number of osteoprogenitor cells present in the bone marrow from adult and aged
      rats as well as their ability to differentiate in vitro and to form bone in vivo.
      We found that the number of adherent colony-forming cells was significantly lower
      (65%) in marrow cells isolated from aged compared with adult rats. Furthermore,
      88% of the colonies obtained from aged rats were alkaline phosphatase (AP)
      positive, whereas virtually all the colonies from adult rats were positive. The
      addition of dexamethasone to the culture medium decreased the proliferation of
      the adherent cells and reduced the number of colonies obtained from both adult
      and aged bone marrow, all of which were AP positive. No significant differences
      were found in the expression of certain major bone cell marker genes as a
      function of donor age. However, dexamethasone treatment increased expression of
      osteopontin (OP) by fivefold. Adult stromal cells not treated with dexamethasone
      and implanted subcutaneously in recipient rats exhibited about 10-fold greater
      formation of bone compared with cells from aged rats. In contrast, dexamethasone
      treated cells exhibited high levels of bone formation, irregardless of donor age
      or the age of the recipient into which the cells were grafted. These studies are
      consistent with a deficit of osteoprogenitor cells in the bone marrow site as a
      contributing, perhaps correctable factor in the decline in bone repair and bone
      mass with age.

PMID- 7736321
TI  - The effect of different hormone replacement therapy regimens on the mechanical
      properties of rat vertebrae.
AB  - The purpose of this study was to examine the effects of estrogen replacement, in
      concert with three different progestin regimens, on the mechanical properties of
      rat lumbar vertebrae. Ninety-two Sprague-Dawley rats (11 months old) were divided
      into six groups for treatment. The first group was an intact control, the second
      group (OVX) was ovariectomized only, and the third group (estrogen-only) was
      ovariectomized and received continuous estrogen through a 17 beta-estradiol
      implant. The remaining groups were ovariectomized and received estrogen and
      progestin (norethindrone, NET) therapy; 3 micrograms of NET was injected daily
      (estrogen plus continuous NET), or 6 micrograms of NET was injected for 14
      consecutive days of a 28-day cycle (estrogen plus cyclic NET), or for 3
      consecutive days of a 6-day cycle (estrogen plus interrupted NET). The animals
      were sacrificed after 6 months, and the vertebrae were dissected out. The
      vertebral processes of the fourth lumbar vertebrae were removed, and the density
      of the vertebral bodies was determined. They were then subjected to compression
      testing. We found that all three estrogen/progestin regimens maintain bone
      density and all mechanical properties at a level indistinguishable from the
      control. However, the cyclic and continuous NET treatment results were, with the
      exception of density, also indistinguishable from those of the ovariectomized
      group. The estrogen plus interrupted NET group on the other hand, has a
      significantly greater compressive modulus and density than the ovariectomized
      group. In conclusion, with respect to the ovariectomized group, the estrogen plus
      interrupted NET treatment resulted in a superior density and compressive
      modulus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736322
TI  - Elevation of alkaline phosphatase activity induced by parathyroid hormone in
      osteoblast-like cells from the spinal hyperostotic mouse TWY (twy/twy).
AB  - We have examined the alkaline phosphatase (AP) activity of primary calvaria
      derived osteoblast-like cells from the twy (tip-toe walking Yoshimura) and normal
      ICR control mouse. The twy mouse displays elevated osseous formation particularly
      in the spine, and the pathophysiological features resemble that of human
      ankylosing spinal hyperostosis. In the proliferative stage of cultured bone
      cells, parathyroid hormone (PTH) stimulation induced the elevation of AP activity
      of both twy and ICR mouse-derived cells. When they reached confluence, the AP
      activity of ICR mouse-derived cells ceased to increase with PTH stimulation. The
      twy mouse-derived cells, however, continued to respond to PTH, with the enzyme
      activity increasing even in the confluent, stationary stage. PTH stimulation also
      increased the intracellular cAMP content of twy mouse-derived cells but it did
      not influence that of ICR mouse-derived cells in the stationary stage. Moreover,
      stimulation with dibutyryl cAMP, but not with phorbol myristate acetate,
      increased the AP activity of both twy and ICR-derived bone cells irrespective of
      culture conditions, either in the proliferative or in the confluent stage. These
      data suggest that the protein kinase A-mediated pathway plays a pivotal role in
      bone cells with PTH stimulation, and that the uninhibited AP activity observed in
      twy mouse-derived bone cells might be due to some deviating process between the
      PTH ligand/receptor interaction and cAMP generation.

PMID- 7736323
TI  - Further characterization of interaction between bone sialoprotein (BSP) and
      collagen.
AB  - Bone sialoprotein (BSP) has an affinity to collagen fibrils [25]. A role of
      carbohydrate chains in the affinity was examined by removing sialic acids of BSP.
      Neuraminidase treatment of the BSP increased the binding to collagen. Binding
      sites of BSP on collagen were examined by biochemical and electron-microscopic
      methods. Purified bovine BSP was labeled with biotin. Collagen alpha chains or
      CNBr peptides were separated by electrophoresis and transfered to nitrocellulose
      membranes. The membranes were incubated with the biotin-labeled BSP, and the
      bound BSP was visualized with avidin conjugated with alkaline phosphatase. The
      labeled BSP was preferentially bound to the alpha 2 chain, and peptides derived
      from alpha 2 chain. In another experiment, the labeled BSP was incubated with
      reconstituted native collagen fibrils. The mixture was put on a copper grid,
      reacted with avidin conjugated with gold particles, and observed with an electron
      microscope. The gold particles were seen mainly within hole zones of the fibrils.
      BSP bound to the alpha 2 chain within the hole zones may regulate the onset of
      calcification at hole zones and the cell binding to collagen fibrils.

PMID- 7736324
TI  - Ectopic mineralized cartilage formation in human undifferentiated pancreatic
      adenocarcinoma explants grown in nude mice.
AB  - Mineralized as well as nonmineralized cartilage-like structures enclosing cells
      resembling chondrocytes were found in human-derived undifferentiated but not in
      poorly differentiated pancreatic adenocarcinoma explants grown in nude mice. The
      structures reacted with anti-mouse IgG but not with antibodies against human
      cytokeratin 19, indicating that the newly formed tissue was of mouse origin. High
      activity of alkaline phosphatase was found in cell layers surrounding the
      structures and in cells embedded in the matrix. The extracellular matrix was
      strongly positive after Sirius red staining, reacted with anti-collagen type II
      antibodies, and the presence of proteoglycans was demonstrated with Alcian blue
      staining and by metachromasia after Giemsa staining. Electron microscopic
      inspection revealed the presence of bundles of both thick collagenous fibrils
      with low levels of fine filamentous material and thin collagenous fibrils with
      high concentrations of filamentous components. The majority of both types of
      matrices was found to be partially or completely calcified. The mean area density
      of the cartilage-like structures in the undifferentiated tumors was 0.31%. The
      frequent formation of the cartilage-like structures in the rapidly growing
      undifferentiated explants and its absence in the slowly growing, more
      differentiated explants suggest that low oxygen tensions in combination with
      altered levels of growth factors, such as members of the transforming growth
      factor beta superfamily, create conditions that induce differentiation of
      fibroblasts to chondrocytes. It is concluded that these human tumors grown in
      nude mice can be used as an in vivo model to study ectopic formation of
      mineralized cartilage.

PMID- 7736325
TI  - Paradoxical effects of phosphate to directly regulate the level of skeletal
      alkaline phosphatase activity in human osteosarcoma (SaOS-2) cells and inversely
      regulate the level of skeletal alkaline phosphatase mRNA.
AB  - Recent studies indicate that the amount of alkaline phosphatase (ALP) activity in
      human osteoblast-line cells is proportional to the concentration of phosphate in
      the culture medium. The current studies were intended to extend those
      observations and to determine whether the effects of phosphate (and phosphate
      esters and analogs) to alter the cellular level of ALP activity, in human
      osteosarcoma SaOS-2 cells, reflected regulation at the level of transcription.
      Consistent with previous findings, we found direct, time- and dose-dependent
      correlations between the concentration of phosphate and the amount of ALP
      activity/mg cell protein (P < 0.05). Surprisingly, we also found a negative
      correlation between the phosphate concentration in the medium and the level of
      skeletal ALP mRNA (e.g., r = -0.98, P < 0.01 at 24 hours). As the highest
      cellular levels of skeletal ALP activity were associated with the lowest levels
      of ALP mRNA, these data indicated that the phosphate-dependent increase in ALP
      activity was not mediated by an increase in transcription and, conversely, that
      the effect of phosphate withdrawal to decrease ALP activity was not mediated by a
      decrease in transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736326
TI  - Interactions between ipriflavone and the estrogen receptor.
AB  - Estrogen replacement therapy is effective in the prevention of postmenopausal
      osteoporosis, and a direct action of 17-beta-estradiol (17 beta E2) on
      osteoblastic and osteoclastic cells has been demonstrated. The inhibition of bone
      resorption by ipriflavone (IP), an isoflavone derivative devoid of estrogenic
      properties but active in potentiating the effects of estrogen on bone tissue, has
      been shown in in vitro and in vivo studies and confirmed by clinical data. To
      investigate the molecular mechanisms that underlie IP effect, we studied the
      possible interactions of IP and its four main in vivo metabolites (I, II, III,
      and V) with the estrogen receptor (ER) in the human preosteoclastic cell line FLG
      29.1, whose growth and function are modulated by the compound. In parallel
      experiments, the human breast cancer cell line MCF7 was also analyzed. IP binding
      sites were demonstrated in the nuclear fraction of FLG 29.1 cells. 17 beta E2 and
      other steroid compounds failed to displace IP binding to intact FLG 29.1 cells.
      Similarly, IP and metabolites I, III, and V were not able to displace 17 beta E2
      binding to intact MCF7 cells, whereas metabolite II showed an IC50 of 61 nM. 17
      beta E2 binding to FLG 29.1 cells was increased after preincubation with
      metabolites I, III, and V. IP and its metabolites did not induce ER-dependent
      gene expression in FLG 29.1 and MCF7 cells transfected with a reporter gene and
      an estrogen response element (ERE).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736327
TI  - 17 beta-estradiol suppresses gene expression of tartrate-resistant acid
      phosphatase and carbonic anhydrase II in ovariectomized rats.
AB  - Tartrate-resistant acid phosphatase (TRACP) and carbonic anhydrase II (CA II) are
      key enzymes responsible for osteoclastic bone resorption. In this study, we
      proposed that estrogen loss in postmenopausal osteoporosis may enhance gene
      expression of TRACP and CA II, and subsequently increase osteoclastic bone
      resorption. We have, therefore, used the ovariectomized rat model of
      postmenopausal bone loss to investigate changes at the gene transcriptional level
      in osteoclastic bone-resorbing enzymes in ovariectomized (OVX) rats, sham
      ovariectomized (S-OVX) rats, and estrogen-treated ovariectomized (E-OVX) rats. We
      have demonstrated for the first time that ovariectomy in rats enhances gene
      expression of TRACP, and CA II. The mRNA levels in OVX were approximately three-
      and four-fold higher, respectively, than those in S-OVX. Enhancement was observed
      1 week after ovariectomy and transcripts remain high during the experimental
      period of 8 weeks. Administration of 17 beta-estradiol to OVX (E-OVX) reduced
      gene expression of these osteoclastic bone-resorbing enzymes 18 hours after
      injection. It appeared that the suppression of the osteoclastic bone-resorbing
      enzymes by 17 beta-estradiol was most effective during the first 1-2 weeks but
      the degree of suppression was reduced at 8 weeks after ovariectomy. In
      conclusion, our results suggest that estrogen prevents bone loss by reducing the
      mRNA levels of osteoclastic bone-resorbing enzymes in bone tissue.

PMID- 7736328
TI  - P-glycoprotein is expressed in parathyroid epithelium and is regulated by
      calcium.
AB  - P-glycoprotein (Pgp), the multidrug resistance (mdr) gene product, has been
      described in normal tissues with diverse physiologic functions. A broad role as a
      transporter protein for toxins, hormones, and physiologic metabolites has been
      provisionally deduced, based on structural analysis and immunoanatomic
      localization. Recently, significant levels of Pgp have been demonstrated in
      endocrine and hormonally responsive tissues and tumors. We examined calcium
      regulated, clonal parathyroid epithelial (PT-r) and endothelial cells (BPE-1) and
      frozen parathyroid tissue from normal human parathyroid, parathyroid hyperplasia,
      parathyroid adenoma, and parathyroid carcinoma for expression of the multidrug
      resistance gene (Mdr1) and Pgp utilizing Northern and Western analysis and
      immunohistochemistry. We also investigated the effect of extracellular calcium
      (eCa) on Pgp expression in PT-r cells at the molecular/cellular level.
      Immunohistochemistry, utilizing three murine monoclonal antibodies (MAbs)--C494,
      JSB-1, and C219--which recognize spatially distinct cytoplasmic epitopes of Pgp,
      revealed strong immunoreactivity in PT-r cells, normal parathyroid, and
      parathyroid hyperplasia, and weak immunostaining in parathyroid adenomas. BPE-1
      cells, endothelial cells, and parathyroid carcinoma were negative. PT-r cells
      showed a single 130 kDa band (120 KDa after glycosidase treatment) on Western
      blot and a 4.6 kb transcript on Northern analysis, consistent with Pgp. Western
      and Northern blot analysis of PTr cells cultured in different eCa concentrations
      showed that eCa up-regulated Pgp expression.

PMID- 7736329
TI  - Bone mineral and body fat measurements by two absorptiometry systems: comparisons
      with neutron activation analysis.
AB  - In 185 adults (68 white and 31 black males, 66 white and 20 black females), total
      body bone mineral density and content and body fat% were measured by two dual
      energy X-ray absorptiometry (DXA) systems--Norland XR-26, software version 2.4,
      and Lunar DPX, software versions 3.4 and 3.6. In a subgroup of 18 males (10
      white, 8 black), body fat% and total body calcium were also measured by in vivo
      neutron activation analysis (IVNA). For total body calcium, the DPX 3.4 system
      gave the highest (1239 g), IVNA the lowest (1195 g), and the XR-26 (1226 g) was
      not significantly different from the DPX 3.6 results. For fat%, the XR-26 system
      gave the highest estimate (23.5%), whereas measurements by the DPX 3.4 and 3.6
      systems (17.4 and 18.2%) were similar to the IVNA measurements (18.3%). BMD and
      BMC measurements by the two DXA systems were highly correlated but significantly
      different for the entire studied population except in the case of BMC in black
      males.

PMID- 7736331
TI  - AIDS and discrimination.

PMID- 7736330
TI  - Ultrasound and densitometry of the calcaneus correlate with the failure loads of
      cadaveric femurs.
AB  - We assessed the bone mineral density (BMD) of 16 matched sets of cadaveric
      proximal femurs and feet using dual-energy x-ray absorptiometry (DXA). We also
      estimated the femoral neck length from the DXA scans. Quantitative ultrasound
      densitometry was used to measure the velocity of sound and broadband ultrasound
      attenuation (BUA) in the calcaneus of each foot. The proximal femurs were then
      tested to failure in a loading configuration designed to simulate a fall with
      impact to the greater trochanter. Femoral neck BMD and trochanteric BMD were
      strongly associated with the femoral failure load (r2 = 0.79 and 0.81,
      respectively; P < 0.001), whereas femoral neck length was modestly correlated
      with femoral failure load (r2 = 0.27, P = 0.04). Calcaneal BMD (r2 = 0.63, P <
      0.001) and BUA (r2 = 0.51, P = 0.002) were also significantly associated with
      femoral failure load. Given the small sample size, we were unable to detect
      differences in the strength of the correlations between the independent
      parameters and femoral failure load. Using linear multiple regression analyses,
      the strongest predictor of femoral failure load was a combination of femoral neck
      BMD and femoral neck length (R2 = 0.85, P < 0.001). Thus, it appears that both
      femoral and calcaneal bone mineral properties may be useful for identifying those
      persons at greatest risk for hip fracture.

PMID- 7736332
TI  - Practice valuation: it's not a matter of if but when.

PMID- 7736333
TI  - Local anesthetic use by dentists in Ontario.
AB  - A mail survey to obtain data on the annual use of local anesthetics in dentistry
      was sent to each of the 6,271 certified dentists in Ontario in 1993. The survey
      asked dentists to identify the different types and total amounts of local
      anesthetics used in their practice yearly. A total of 2,426 dentists responded to
      the survey. Based on extrapolation of the data collected, it is estimated that
      more than 11,000,000 cartridges of local anesthetic are administered annually by
      dentists in Ontario. The distribution of use of specific types of local
      anesthetics and vasoconstrictors was also determined. Lidocaine with 1:100,000
      epinephrine accounted for 23.4 per cent of all cartridges used, followed by
      articaine with 1:200,000 epinephrine (19.9 per cent), articaine with 1:100,000
      epinephrine (17.9 per cent), prilocaine with 1:200,000 epinephrine (16.4 per
      cent), mepivacaine with 1:20,000 levonordefrin (6.4 per cent), and mepivacaine
      plain (6.3 per cent). Other anesthetics were used to a lesser degree. Further
      analysis revealed no statistically-significant differences in the use of local
      anesthetics among dentists who responded to the survey and non-responders. The
      results of this survey document the current use of local anesthetics in
      dentistry.

PMID- 7736334
TI  - Maxillary nerve block: a case report and review of the intraoral technique.
AB  - Maxillary nerve blockade is not commonly used by general practitioners due to a
      lack of experience with the techniques involved and the fear of iatrogenic
      damage. Nevertheless, it represents an excellent method of producing profound
      anesthesia in the maxilla, with definite indications in selected instances. The
      anatomy and techniques associated with the maxillary block, as well as the
      indications, contraindications and complications are reviewed, and the use of the
      greater palatine foramen approach to treat a patient with a facial abscess is
      described.

PMID- 7736335
TI  - A 21 year retrospective study of reports of paresthesia following local
      anesthetic administration.
AB  - A retrospective study of paresthesia following the injection of local anesthetic
      in dentistry was conducted by examining every report of paresthesia recorded by
      Ontario's Professional Liability Program from 1973 to 1993, inclusive. Only those
      cases where surgery was not conducted were considered in this study. The
      parameters examined included patient age and gender, needle gauge, site of
      injection, area affected, report of pain or any additional symptoms, and the type
      of local anesthetic used. From 1973 to 1993, there were 143 reports of
      paresthesia not associated with surgery. There were no significant differences
      found with respect to patient age, patient gender, or needle gauge. All reports
      involved anesthesia of the mandibular arch, with the tongue most frequently
      reported to be symptomatic, followed by the lip. Pain was reported in 22 per cent
      of the cases. Paresthesia was reported most often following the injection of
      articaine and prilocaine. In 1993 alone, there were 14 reports of paresthesia not
      associated with surgery. This can be projected to an incidence of 1:785,000
      injections. Articaine was administered in 10 of these cases or prilocaine in the
      other four. The observed frequencies of paresthesia following the administration
      of articaine (p < 0.002) or prilocaine (p < 0.025) were significantly greater
      than the expected frequencies for these agents, based on the distribution of
      local anesthetic use in Ontario in 1993. These results are consistent with the
      suggestion that local anesthetic formulations may have the potential for mild
      neurotoxicity. Further studies are needed to investigate the mechanisms for this,
      and to determine whether similar findings would be found elsewhere.

PMID- 7736336
TI  - The Canadian Dental Association guidelines on chewing gum recognition.

PMID- 7736337
TI  - [Oral candidiasis: diagnosis and drug therapy].
AB  - Oral candidiasis is the most frequently observed oral mycosis. It can be
      manifested as a variety of clinical symptoms, and both local and systemic factors
      may contribute to its development. A confirmation of this infection depends upon
      the use of appropriate diagnostic tests, in addition to the presence of clinical
      signs and symptoms. The choice of antifungal agent depends on the location,
      severity and chronicity of the lesions, as well as the health status of the
      patient. Oral candidiasis generally responds well to pharmacological treatment.
      If the infection is persistent or recurrent, a possible underlying homeostatic
      disturbance should be investigated.

PMID- 7736338
TI  - The 1993 Upjohn Award Lecture. Quinolinic acid induced brain neurotransmitter
      deficits: modulation by endogenous excitotoxin antagonists.
AB  - Excitotoxins constitute a group of agents that are capable of activating
      excitatory amino acid receptors and producing axonsparing neuronal lesions. Focal
      injections of the exogenous excitotoxins kainic acid and ibotenic acid result in
      depletion of neurotransmitter markers in neuronal cell bodies located in areas of
      injection or in terminal zones of their projections. The discovery of endogenous
      agents that behave as excitotoxins has generated interest in the idea that
      excitotoxicity may contribute to the neuronal degeneration associated with a
      number of neurological diseases (Alzheimer's disease, Huntington's disease,
      Parkinson's disease) which involve selective neurotransmitter deficits.
      Quinolinic acid (QUIN), a pyridine dicarboxylic acid and metabolite of
      tryptophan, which has been detected in the central nervous system (CNS), behaves
      as an excitotoxin. In the mammalian brain QUIN has been localized to glial and
      immune cells, and its content increases with age. The neuro-excitatory and
      neurotoxic actions of QUIN are mediated via the Mg(2+)-sensitive N-methyl-D
      aspartate (NMDA) receptor. The toxicity of QUIN, like that of kainate, but not
      ibotenate, is dependent on the presence of an intact glutamate-aspartate afferent
      input to the target area. Focal injections of QUIN into the nucleus basalis
      magnocellularis (nbM), a major source of cholinergic innervation to diencephalic
      areas, produce sustained loss of cholinergic neuron markers in the neocortex and
      amygdala. The neurotoxic action of QUIN on nbM results in an impairment of
      performance on memory-related tasks. Cortical and amygdaloid projecting
      cholinergic neurons show differential sensitivity to QUIN and other excitotoxic
      agents. This factor may partly explain the reported discrepancy between mnemonic
      deficits and the loss of cholinergic markers in the cerebral cortex induced by
      intra-nbM injections of certain excitotoxins. Cortical muscarinic receptor
      function is not significantly influenced by QUIN injections into the nbM
      producing loss of cortical cholinergic neurons. In the striatum, focal QUIN
      injections have been found to largely replicate the neurotransmitter deficits
      prevailing in Huntington's disease, an inherited movement disorder. Intrastriatal
      QUIN produces a profound loss of the NADPH diaphorase staining neurons in the
      area of injection but relatively spares these in the adjacent transition zone.
      QUIN is also highly damaging to the striatopallidal enkephalinergic neurons.
      However, at doses that are neurotoxic to striatal neurons, QUIN and several other
      excitotoxins produce significant elevations in enkephalin levels both in the
      striatum and globus pallidus. This elevation reflects the presence of a
      plasticity in the striatal enkephalinergic neuron population. The metabolic
      pathway yielding QUIN produces a number of intermediates that act as excitotoxin
      antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7736339
TI  - The 1993 Borden Award Lecture. Fatty acid requirements of the newborn.
AB  - Arachidonic acid (20:4 omega-6) and docosahexaenoic acid (22:6 omega-3) are
      deposited in large amounts in the nonmyelin membranes of the developing central
      nervous system (CNS). Inadequate supplies of omega-6 and omega-3 fatty acids
      during CNS development are of concern because of possible long-term changes in
      learning ability and reduced visual function. Although all of the omega-6 and
      omega-3 fatty acids in the CNS are ultimately derived from the diet, the pathways
      for transport or transfer from the plasma to the CNS are not known. Current
      evidence suggests that the newborn is able to synthesize 20:4 omega-6 and 22:6
      omega-3 from linoleic acid (18:2 omega-6) and linolenic acid (18:3 omega-33),
      respectively; however, it is not yet clear if synthesis occurs in the liver prior
      to transfer to the CNS, or directly in the CNS. Further understanding of the
      roles of 20:4 omega-6 and 22:6 omega-3 in CNS metabolism, pathways of omega-6 and
      omega-3 fatty acid transport and CNS uptake, and the effects of premature birth
      on fatty acid metabolism is needed to facilitate future studies on the importance
      of 20:4 omega-6 and 22:6 omega-3 in infant nutrition.

PMID- 7736340
TI  - The 1994 Merck Frosst Award. Mechanisms of nonsteroidal anti-inflammatory drug
      (NSAID) induced gastrointestinal damage--potential for development of
      gastrointestinal tract safe NSAIDs.
AB  - Nonsteroidal anti-inflammatory drugs are widely used for the treatment of
      osteoarthritis and rheumatoid arthritis, but their ability to cause
      gastrointestinal bleeding is a significant limitation to this use. A better
      understanding of the pathogenesis of gastric and intestinal injury induced by
      these agents will permit the rational design of anti-inflammatory drugs that
      spare the gastrointestinal tract. In this review, the mechanisms through which
      nonsteroidal anti-inflammatory drugs are believed to cause gastrointestinal
      ulceration are reviewed. Several strategies that are being employed to develop
      gastrointestinal-sparing drugs are outlined.

PMID- 7736341
TI  - The physicochemistry of [H+] and respiratory control: roles of PCO2, strong ions,
      and their hormonal regulators.
AB  - I describe how the dietary intake of strong ions potentially affects the
      regulation of ventilation and the PCO2 of body fluids in two ways. First,
      changing the dietary intake of NaCl can alter the concentration difference
      between strong cations and strong anions (the [SID] of Stewart) of body fluids.
      Experimental observations indicate that the [SID] in brain fluids or
      cerebrospinal fluid ([SID]CSF) could be the stimulus to central chemoreceptors.
      [SID]CSF consistently predicts ventilatory regulation of PCO2, whereas [H+]CSF
      does not. PCO2 acts as a stimulus to ventilation independently of [SID]CSF and
      possibly at higher as well as lower centers of the nervous system. I relate the
      concept of [SID] regulation of arterial PCO2 to the alphastat hypothesis of
      protein function, respiratory control, and [H+] homeostasis. Second, altering the
      dietary intake of NaCl changes the levels of hormones involved in salt and water
      balance. Angiotensin II acts centrally to stimulate ventilation. Evidence for the
      roles of both the renal and brain renin-angiotensin systems in respiratory
      control, and the modulation of respiratory control by vasopressin are reviewed.
      These peptide systems probably act via circumventricular organs of the brain to
      affect respiratory control and (or) by changing strong ion concentrations in
      brain fluids. Questions to be resolved on the role of [SID]CSF and hormones in
      respiratory adaptations, and experiments required to improve our understanding of
      the control of ventilation, are addressed in the concluding comments.

PMID- 7736342
TI  - Effect of dexamethasone treatment on the biotransformation of glyceryl
      trinitrate: cytochrome P450 3A1 mediated activation of rat aortic guanylyl
      cyclase by glyceryl trinitrate.
AB  - It is generally accepted that organic nitrates act via vascular biotransformation
      to an activator of guanylyl cyclase (presumably NO), resulting in increased
      cyclic GMP accumulation and vascular smooth muscle relaxation. Previously, we
      have shown that cytochrome P450 can mediate the biotransformation of glyceryl
      trinitrate (GTN) and that at least a portion of this biotransformation results in
      the formation of an activator of guanylyl cyclase. To assess the role of the
      cytochrome P450 3A subfamily in this phenomenon, we treated male and female rats
      with dexamethasone (DEX) (150 mg/kg, i.p., daily for 3 days). Under anerobic
      conditions, hepatic microsomal biotransformation of GTN was increased three-fold
      in DEX-treated male rats compared with all other treatment groups. Incubation of
      aortic 100,000 x g supernatant fraction from untreated rats (as a source of
      guanylyl cyclase) with GTN and hepatic microsomes from all groups resulted in
      concentration-dependent increases in guanylyl cyclase activation. Microsomes from
      DEX-treated male and female rats demonstrated a significantly greater activation
      of guanylyl cyclase compared with microsomes from untreated males and females.
      Furthermore, GTN-induced guanylyl cyclase activation mediated by microsomes from
      DEX-treated male and female rats was markedly inhibited by a polyclonal antibody
      raised to rat CYP3A1. Since CYP3A2 is absent or very low in hepatic microsomes
      from DEX-treated adult female rats, this identifies CYP3A1 as an isoform capable
      of biotransforming GTN to an activator of guanylyl cyclase. Similarly, CYP2C11
      was identified as an isoform capable of biotransforming GTN to an activator of
      guanylyl cyclase, since monoclonal antibody to CYP2C11 inhibited GTN-induced
      activation of guanylyl cyclase mediated by microsomes from control male
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736343
TI  - Studies of acute effect of prolactin on distribution of absorbed calcium and long
      term effect on calcium balance in weaned, young, and sexually mature rats.
AB  - An acute effect of a single dose of 0.02 mg prolactin/100 g body weight
      administered intraperitoneally on distribution of absorbed calcium and the effect
      of daily subcutaneous injections of 0.25 mg prolactin/100 g body weight for 13
      days on calcium balance were assessed in weaned, young, and mature female rats.
      The acute administration of prolactin failed to affect distribution of absorbed
      calcium at 2 h after instillation of test solution. In contrast, the daily
      injection of a lower dose of prolactin over 13 days significantly decreased fecal
      and urinary excretion of 45Ca, an index of absorbed calcium, in mature rats,
      while having no effect on muscle and tibial 45Ca contents. In young rats, in
      addition to a reduction in the urinary 45Ca excretion, prolactin decreased the
      gastrocnemius muscle total calcium content from 7.28 +/- 0.37 to 5.58 +/- 0.37
      mumol/g dry weight (p < 0.01) while increasing tibial calcium content from 6.65
      +/- 0.18 to 7.35 +/- 0.15 mmol/g dry weight (p < 0.01). Bone formation
      (represented by serum alkaline phosphatase) in weaned rats was significantly
      elevated by prolactin, but bone resorption (represented by urinary
      hydroxyproline) was not altered. It could be concluded that prolonged
      administration of prolactin decreased calcium excretion in mature rats and
      increased bone formation and tibial calcium content in growing rats.

PMID- 7736344
TI  - Body-core temperature decreases during hypoxic hypoxia in Long-Evans and
      Brattleboro rats.
AB  - In newborn mammals, hypoxic hypoxia produces a regulated decrease in body-core
      temperature, the mechanism of which is unknown. Since plasma and cerebrospinal
      fluid levels of arginine vasopressin increase during hypoxemia and
      intracerebroventricular administration of arginine vasopressin decreases body
      core temperature, it has been hypothesized that an increase in central arginine
      vasopressin may mediate this response. Experiments were therefore carried out to
      test the hypothesis that the body-core temperature response to hypoxic hypoxia
      would be different in Brattleboro rats (which lack arginine vasopressin
      containing cells in the central nervous system) compared with that observed in
      Long-Evans rats (which have arginine vasopressin containing cells in the central
      nervous system). Both mild (15% oxygen) and severe (10% oxygen) hypoxic hypoxia
      decreased body-core temperature in both strains of rats, the decrease actually
      being accentuated in the Brattleboro rats. Thus, our data do not support the
      hypothesis that an increase in central arginine vasopressin mediates the
      regulated decrease in body-core temperature during hypoxic hypoxia in rats.

PMID- 7736345
TI  - The role of stomachal digestion on the pharmacological activity of plant
      extracts, using as an example extracts of Harpagophytum procumbens.
AB  - Various researchers have described anti-inflammatory activity of aqueous extracts
      of devil's-claw (Harpagophytum procumbens DC.). In this study the extent of the
      anti-inflammatory activity of an aqueous extract prepared from cryoground fresh
      plant and administered intraperitoneally, per os (by gavage), and intraduodenally
      was determined in rats. The anti-inflammatory properties were assessed by
      applying the carrageenan-induced edema test. The results obtained indicated that
      intraperitoneal pretreatment with an aqueous extract of H. procumbens
      significantly reduced the carrageenan-induced edema at 400 and 800 mg/kg 4 h
      after carrageenan injection (45 and 65% inhibition, respectively). When
      administered orally (by gavage), the extracts were inefficient. This result could
      be attributed to the time in transition in the stomach, where the pH is acidic,
      causing a decrease of the activity of the extract. This inference is consistent
      with the results obtained by other authors, showing the absence of extract
      activity when it was treated in an environment of pH 1 and 37 degrees C (similar
      to the physicochemical conditions found in the stomach) and then administered
      intraperitoneally. Intraduodenal pretreatment with the aqueous extract
      significantly reduced the carrageenan-induced edema at 200, 400, and 1600 mg/kg 6
      9 h after carrageenan injection (43, 60, and 41% inhibition, respectively). The
      presence of extract activity after intraduodenal administration supports the
      assumption that transition of the extract through the stomach leads to loss of
      activity.

PMID- 7736346
TI  - Effects of vanadium treatment on the alterations of cardiac glycogen
      phosphorylase and phosphorylase kinase in streptozotocin-induced chronic diabetic
      rats.
AB  - Supersensitivity to isoproterenol (ISO) induced activation of cardiac
      phosphorylase in diabetic rat heart has been previously demonstrated and was also
      reproduced in this study. To explore further the nature of this supersensitivity,
      we examined the activity of phosphorylase kinase and the level of cyclic AMP
      (cAMP) in this tissue. We observed a significantly enhanced activation of
      phosphorylase kinase but no increase in cAMP levels in response to ISO
      stimulation in diabetic rat heart, suggesting that the supersensitivity of
      phosphorylase activation in diabetic heart may result from an enhanced activation
      of phosphorylase kinase that does not involve the cAMP pathway. On the other
      hand, perfusion of diabetic rat heart with verapamil (5 x 10(-8) M) prior to ISO
      stimulation abolished the enhanced cardiac phosphorylase activation, suggesting a
      role for calcium in the supersensitivity of phosphorylase activation.
      Furthermore, treatment of the diabetic rats with an insulin-like compound,
      vanadyl sulphate, completely abolished the enhanced cardiac phosphorylase
      activation and restored the increase in ISO-induced cAMP elevation in diabetic
      heart. The present study has provided further information on the changes of
      phosphorylase activation in the diabetic rat heart and demonstrated beneficial
      effects of vanadyl sulphate on the pathway leading to phosphorylase activation in
      diabetic rat heart.

PMID- 7736347
TI  - Alterations in hepatic adrenergic receptor status in Rana sylvatica in response
      to freezing and thawing: implications to the freeze-induced glycemic response.
AB  - In Rana sylvatica, freeze-induced liberation of glucose from hepatic glycogen
      stores plays a critical role in conferring freeze tolerance. To determine whether
      an alteration in hepatic adrenergic receptor status, which dictates catecholamine
      directed hepatic glycogenolytic responses, is involved in the glycemic response
      to freezing, hepatic alpha 1, alpha 2, and beta 2 adrenergic receptors and
      calcium transport were characterized by radioligand and radioisotopic techniques,
      respectively, in plasma membranes isolated from the livers of control, -2.5
      degrees C-exposed, and frozen-thawed frogs. The three adrenergic receptors
      display marked and different patterns of changes in response to freezing, with
      two distinct receptor shifts clearly evident. In the control state, the beta 2
      adrenergic receptor dominates over the alpha 1 receptor. At 12 h, beta 2
      adrenergic receptor dominance intensifies by a receptor shift involving a
      decrease in the alpha 1 and alpha 2 adrenergic receptors. Coincident with the
      initiation of the glycemic response, this early shift may be causally related to
      it. At 24 h, the alpha 1 adrenergic receptor dominates, achieved by a receptor
      shift involving a decrease in the beta 2 adrenergic receptor and an increase in
      the alpha 1 and alpha 2 adrenergic receptors. This shift may be related to the
      maintenance of the glycemic response. Receptor shifts are associated with changes
      in calcium transport, which accentuate them. The thawed state is characterized by
      recovery of alpha, but not beta 2, receptor expression correlatable with, and
      perhaps allowing, a switch to hepatic glycogenesis. The role of thyroid hormone,
      whose levels are lower in the frozen state, in inducing receptor shifts is
      discussed.

PMID- 7736348
TI  - Effect of bradykinin B2 receptor antagonist and indomethacin on natriuretic and
      hypotensive responses to atrial natriuretic factor.
AB  - The effects of inhibition of bradykinin and prostaglandin on the renal and blood
      pressure responses to atrial natriuretic factor (ANF) were studied in
      anesthetized rats. Intraarterial infusion of the receptor antagonist D
      Arg[Hyp3,Thi5,8,D-Phe7]bradykinin (BKA) at 14 micrograms/min, a rate sufficient
      to block the hypotensive response to 250 micrograms of bradykinin, did not affect
      the natriuresis due to injection of ANF (UNaV: control, before ANF, 393 +/- 101,
      after ANF, 2322 +/- 400 nmol/min; BKA, before ANF, 261 +/- 72, after ANF, 2259 +/
      390 nmol/min). In contrast, infusion of indomethacin (Indo) reduced the level of
      sodium excretion both before and especially after ANF administration (UNaV: Indo,
      before ANF, 75 +/- 15, after ANF, 320 nmol/min). The effect of combining BKA with
      Indo was not different from the effect of Indo alone (UNaV: BKA + Indo, before
      ANF, 119 +/- 26, after ANF, 469 +/- 167 nmol/min). The bradykinin antagonist,
      with or without Indo, was associated with significant hypotension relative to
      control. Indo, both in the absence and presence of the antagonist, was associated
      with a progressive decrease in blood pressure compared with control. However, in
      each the hypotensive responses to ANF were not different from those in the
      control group. We conclude that under the present experimental conditions
      bradykinin does not modify ANF-induced natriuresis. However, inhibition of
      prostaglandin synthesis by Indo is associated with renal salt retention, reducing
      natriuresis both before and after ANF administration.

PMID- 7736349
TI  - Potential defect in the vascular control of nonshivering thermogenesis in the
      obese Zucker rat hind limb.
AB  - Vascular control of nonshivering thermogenesis in the perfused hind limb of obese
      and lean Zucker rats were compared using two vasoconstrictors, norepinephrine and
      serotonin. For hind limbs of both phenotypes, norepinephrine infusions resulted
      in a dose-dependent uninterrupted increase in perfusion pressure and a biphasic
      change in oxygen uptake (VO2), characterized by a stimulation at low
      concentrations, and an increasing inhibition at higher concentrations that
      gradually overcame the stimulation in a dose-dependent manner. At concentrations
      of norepinephrine greater than 1 microM, the inhibitory effect predominated and
      gave rise to values for VO2 less than basal. The obese hind limb had a lower
      basal VO2 and a lower maximal VO2 mediated by norepinephrine than the lean rat,
      but these differences appeared to relate largely to the lower muscle mass and
      higher content of fat of the obese hind limb. Serotonin infusions resulted in
      dose-dependent increase in perfusion pressure and an accompanying decrease in
      VO2. Pressure changes were identical for the obese and lean hind limbs, but the
      decrease in VO2 due to serotonin was greater in the hind limbs from the lean
      rats, and this difference remained when the data were expressed in terms of
      muscle mass perfused. It is concluded that the relatively lower content of muscle
      of the obese hind limb accounts for its lower basal and lower maximal
      norepinephrine-mediated thermogenesis. In addition, an intrinsic defect in obese
      hind limb muscle response to serotonin is present, which may be indicative of a
      decrease in the potential for vasoconstrictor-regulated thermogenesis that could
      have implications for whole-body energy balance by the obese phenotype.

PMID- 7736351
TI  - Positive inotropic effect of adrenaline on potassium contractures in tonic
      skeletal muscle fibres of the frog.
AB  - K+ contractures were elicited in small bundles of tonic skeletal muscle fibres of
      the frog. Adrenaline (1 microM) increased the amplitude of K+ contractures in a
      [K+]o-dependent manner: maximal effects were produced between 20 and 60 mM [K+]o.
      In contrast, we found no effect of adrenaline on K+ contractures of twitch
      fibres. The potentiating effect of adrenaline depended on [Ca2+]o. Increasing
      [Ca2+]o from 1.8 to 10 mM doubled the positive inotropic effect of adrenaline. In
      a nominally Ca2+ free saline, adrenaline had no potentiating effect. The Ca2+
      channel blockers nifedipine (20 microM) and Ni2+ (1.8 mM) reversibly reduced the
      amplitude of the tonic phase of K+ contractures and blocked the potentiation by
      adrenaline. The mechanical effects of adrenaline cannot be explained by changes
      in the membrane potential, as revealed by intracellular recordings at several
      [K+]o. It was concluded that the potentiating effect of adrenaline in tonic
      muscle fibres of the frog may be mediated through Ca2+ channels.

PMID- 7736350
TI  - Alpha 1a-adrenergic receptor mediated positive chronotropic effect in right atria
      isolated from rats.
AB  - Experiments in right atria isolated from adult male rats were designed to
      determine which of the alpha 1-adrenergic receptor (alpha 1-AR) subtypes are
      involved in the positive chronotropic effect of phenylephrine, an alpha 1-AR
      agonist. Chloroethylclonidine (CEC), an irreversible alpha 1b-, alpha 1c-, and
      alpha 1d-AR antagonist, did not alter the efficacy or potency of phenylephrine;
      however, CEC did elicit a concentration-dependent negative chronotropic effect
      and reduce the absolute maximum spontaneous rate observed in the presence of
      phenylephrine. WB4101, a competitive alpha 1a- and alpha 1c-AR-selective
      antagonist, did not alter basal spontaneous rate or the efficacy of
      phenylephrine, but it did produce a significant rightward shift of the
      phenylephrine concentration-response curve. Phenoxybenzamine, an irreversible
      nonselective alpha-AR antagonist, elicited a concentration-dependent negative
      chronotropic effect, a significant rightward shift of the phenylephrine
      concentration-response curve, and a reduction in the efficacy of phenylephrine.
      The chronotropic action of the beta-adrenergic agonist isoproterenol was not
      affected by CEC, WB4101, or phenoxybenzamine. These data suggest that the
      positive chronotropic effect of alpha 1-adrenergic agonists in rat right atria is
      mediated via stimulation of alpha 1a-ARs.

PMID- 7736352
TI  - Inhibition by antidepressants of glibenclamide-sensitive K+ currents in follicle
      enclosed Xenopus oocytes.
AB  - Effects of antidepressive drugs on glibenclamide-sensitive K+ currents were
      investigated using follicle-enclosed Xenopus oocytes. Antidepressive drugs,
      imipramine, desipramine, and amitriptyline, inhibited the K+ currents with IC50
      (microM) values of 35.4, 39.7, and 87.7, respectively. The K+ current blocking
      actions of antidepressants appear to be associated with their local anesthetic
      related structures.

PMID- 7736353
TI  - The plasmid profiles of fish pathogenic isolates of Aeromonas salmonicida, Vibrio
      anguillarum, and Vibrio ordalii from the Atlantic and Pacific coasts of Canada.
AB  - The plasmid profiles of oxytetracycline- and streptomycin-resistant isolates of
      Aeromonas salmonicida, Vibrio anguillarum, and Vibrio ordalii were examined by
      agarose gel electrophoresis. Bacterial isolates were from disease outbreaks in
      fish on the Atlantic and Pacific coasts. Resistant isolates were examined when
      grown in the presence and absence of antibiotic. Alkaline lysis methods were used
      for plasmid isolation. Vibrio spp. were predominantly plasmidless, except for a
      47-kilobase (kb) plasmid. Atlantic coast isolates of A. salmonicida possessed
      four or six plasmids, with four smaller plasmids ranging in size from 4.3 to 8.1
      kb being consistently observed. The plasmid profiles of antibiotic-sensitive ATCC
      strains were identical. The plasmid profiles of the Pacific coast isolates of A.
      salmonicida varied slightly from those of the Atlantic coast isolates with six
      plasmids observed, ranging in size from 4.2 to 8.9 kb. Resistance to the
      antibiotics was not altered following plasmid curing experiments and resistance
      was not transferable to Escherichia coli. Thus, resistance to oxytetracycline and
      streptomycin did not appear to be plasmid mediated.

PMID- 7736354
TI  - Protection against bacteriocin 28b in Serratia marcescens is apparently not
      related to the expression of an immunity gene.
AB  - The gene encoding bacteriocin 28b from Serratia marcescens N28b (bss gene) has
      been cloned in Escherichia coli and its nucleotide sequence has been determined.
      The genetic determinants coding for other well-characterized bacteriocins from
      enterobacteria (colicins) are located in plasmids and they have always been shown
      to contain a gene responsible for immunity located downstream from the
      bacteriocin structural gene. In some cases there is another gene located
      downstream from the immunity gene, which is responsible for bacteriocin release.
      Analysis of bacteriocin 28b release and the sensitivity to this bacteriocin of E.
      coli strains harbouring recombinant plasmids containing the bss gene showed that
      bacteriocin 28b is not released from the cell in these strains and that their
      phenotypic insensitivity is not associated with any region close to the
      structural gene. The nucleotide sequence of the region downstream from the bss
      gene contains two putative open reading frames transcribed in the opposite
      direction to the bss gene. These open reading frames apparently encode proteins
      that seem not to be involved in bacteriocin immunity or release. Moreover, a S.
      marcescens N28b genomic library was screened and no immunity gene was found.
      Therefore, bacteriocin 28b differs greatly from the bacteriocins from other
      enterobacteria, and in the following senses it is unique: firstly, the gene
      encoding bacteriocin 28b seems to be located on the chromosome, and secondly,
      insensitivity to this bacteriocin in S. marcescens N28b is not associated with
      the expression of an immunity gene.

PMID- 7736355
TI  - Genetic diversity of N2-fixing bacteria associated with rice roots by molecular
      evolutionary analysis of a nifD library.
AB  - The rhizosphere of wetland rice has significant N2-fixing activity. It has been
      suggested that N2 fixation in the rice root zone is associated with the activity
      of various N2-fixing heterotrophic bacteria that inhabit the rice rhizosphere.
      Because of the generic diversity, many different isolation media and conditions
      are required to count and isolate these bacteria. In an attempt to overcome any
      bias from culture-dependent methods we amplified nifD segments from crude rice
      root DNA by the polymerase chain reaction. The nifD fragments were then cloned
      into a pT7 Blue T-vector to construct a nifD library. Sixteen cloned nifD genes
      chosen at random from the library were sequenced. A comparison with published
      sequences indicated the presence of seven novel groups of NifD proteins, which
      implies the existence of at least seven components in the diazotrophic community
      of rice roots, dominated mainly by proteobacteria. We also observed genetic
      variability within the clusters, which suggests the coexistence of many closely
      related bacterial lineages. However, we did not find Azospirillum-like nifD
      clones, although many reports indicated the widespread presence of Azospirillum
      spp. Therefore, it remains to be clarified whether Azospirillum species are the
      widespread N2-fixing bacteria in rice roots.

PMID- 7736356
TI  - Pattern of polar extension of the cell wall in the fission yeast
      Schizosaccharomyces pombe.
AB  - The indirect fluorescent-antibody technique has been used to establish the
      pattern of polar extension in the fission yeast Schizosaccharomyces pombe 160
      over a complete cell cycle in liquid medium, thus avoiding the possibility of
      perturbations being introduced by growth on an agar pad, which is the technique
      used in most other investigations. Nearly all of the cells (about 98%) showed
      more growth at the old end than at the new end that was formed by cleavage of the
      septum at the previous division. Importantly, there was no evidence of the
      abnormal growth pattern (i.e., the significant contribution of new ends to
      extension) in cells of S. pombe growing on agar pads reported by Miyata et al.
      (H. Miyata, M. Miyata, and B.F. Johnson. 1986. Can. J. Microbiol. 32: 528-530 and
      1990. Can. J. Microbiol. 36: 390-394). In addition, extension over the cycle was
      inversely related to birth length (cells shorter than the mean at birth tended to
      produce daughter cells longer than themselves and vice versa), there was a small
      but significant asymmetry in the position of the septum, and the time of
      initiation of extension at the new end was estimated at about 0.24 of the cycle.

PMID- 7736357
TI  - A full factorial analysis of nine factors influencing in vitro antagonistic
      screens for potential biocontrol agents.
AB  - The effect of nine factors on the outcome of classic in vitro screens testing the
      antagonistic action of endophytic bacterial isolates from grape vines against
      virulent Agrobacterium vitis has been examined. These factors were (i) the strain
      of A. vitis, (ii) the strain of endophyte, (iii) the growth medium of the
      pathogen, (iv) the growth medium of the endophyte, (v) the temperature of growth
      of the pathogen, (vi) the temperature of growth of the endophyte, (vii) the pH of
      growth of the pathogen, (viii) the pH of growth of the endophyte, and (ix) the
      medium of the assay plate. Analyses of variance of the full factorial design
      incorporating main effects and two- and three-way interactions accounted for 66%
      of the variance. All nine factors had a significant effect on the diameter of
      inhibition zones (p < 0.001). An examination of the three-way interactions
      revealed that generalizations were difficult to draw; each target agrobacterium
      had a specific response to a given antagonistic isolate. It was possible to
      determine that the growth history of bacterial strains, before they were
      administered to an assay plate to test for antagonism (especially the composition
      of the growth medium and the temperature of growth), had a profound effect on the
      outcome of the test. Generally the more chemically defined media produced less
      inhibition whereas the lower growth temperature of 15 degrees C produced more
      inhibition. These findings could be relevant to in situ inhibitory activity. The
      method used to conduct the inhibitory screen (order of strain application and the
      medium of the assay plate) had a profound influence on the results. These
      influences add to the caution necessary in the use of in vitro antagonistic
      screens for finding successful biocontrol agents.

PMID- 7736358
TI  - Biodegradation of trichloroethylene by Mycobacterium vaccae.
AB  - Nonproliferating cells of Mycobacterium vaccae that were grown on propane could
      mineralize limited amounts of trichloroethylene. Intermediates in the
      biodegradation of trichloroethylene were 2,2,2-trichloroethanol and 2,2,2
      trichloroacetaldehyde. Trichloroethanol was completely degraded when added to a
      nonproliferating cell suspension of Mycobacterium vaccae. Addition of toluene to
      the reaction mixtures effected a 50% increase in the mineralization of
      [14C]trichloroethylene.

PMID- 7736359
TI  - Diversity of lactate metabolism in halophilic archaea.
AB  - D-Lactate is readily used as a substrate for the growth of species of halophilic
      archaea belonging to the genera Haloferax and Haloarcula. L-Lactate was used by
      Haloferax species (Haloferax volcanii, Haloferax mediterranei) only when a
      substantial concentration of the D-isomer was also present in the medium. On the
      enzymatic level, considerable diversity was found in the lactate metabolism of
      the different representatives of the Halobacteriaceae. At least three types of
      lactate dehydrogenases were detected in halophilic archaea. A high level of
      activity of an NAD-linked enzyme was present constitutively in Haloarcula
      species, and a low level of activity was also detected in Haloferax mediterranei.
      NAD-independent lactate dehydrogenases, oxidizing L-lactate and D-lactate with
      2,6-dichlorophenol-indophenol as electron acceptor, were detected in all nine
      species tested, but L-lactate dehydrogenase activity in Halobacterium species was
      very low, and Haloarcula species, which possess a high level of activity of NAD
      linked lactate dehydrogenase, showed very low activities of both NAD-independent
      D- and L-lactate dehydrogenase. An inducible lactate racemase, displaying an
      unusually high pH optimum, was found in Haloferax volcanii. Lactate racemase
      activity was found constitutively in Haloarcula species, but no activity was
      detected in Halobacterium species and in Haloferax mediterranei.

PMID- 7736360
TI  - The Part II examination: political exercise or national standard?

PMID- 7736361
TI  - CMA and divisions consider payment options.

PMID- 7736362
TI  - Variations in hysterectomy rates in Ontario.

PMID- 7736363
TI  - Denied training, physician heartened by support.

PMID- 7736364
TI  - Adopted children exposed to cocaine in utero: confounding factors.

PMID- 7736365
TI  - Forceps use: a gender issue?

PMID- 7736366
TI  - Right-to-die rhetoric.

PMID- 7736367
TI  - The medical hazards of television sports.

PMID- 7736368
TI  - Female circumcision not in Qur'an.

PMID- 7736369
TI  - The breast cancer research scandal: addressing the issues.
AB  - The three claims put forward by Dr. Roger Poisson to rationalize his enrollment
      of ineligible subjects in clinical trials do not justify research fraud. None the
      less, certain lessons for the conduct of clinical research can be learned from
      the affair: experimental therapies should be made available to technically
      ineligible subjects when no effective therapy exists for their disease; further
      research must investigate the possible benefits of clinical-trial participation;
      broadly based, pragmatic trials must be regarded as the ideal model; and each
      eligibility criterion in a clinical-trial protocol should be justified.

PMID- 7736370
TI  - Core and comprehensive health care services: 2. Quality-of-care issues.
AB  - Health care services are being evaluated and redefined. Terms such as "medically
      necessary" and "comprehensive" are being supplanted by "core", "basic" and
      "optional." Quality-of-care concepts and analysis can assist decision making
      about which services should be insured, core services. A service is more likely
      to remain or become insured, and core to the system if it satisfies the key
      dimensions of high quality: effectiveness, appropriateness, efficiency, patient
      acceptance and safety. Quality of care, combined with ethical and economic
      considerations, provides an analytic framework for deciding whether services
      should be insured.

PMID- 7736371
TI  - Diffusion of standards of care for cancer pain.
AB  - The authors report the results of a symposium on improving the standards of care
      for patients with cancer pain. The symposium was sponsored by the Advisory
      Committee on Cancer Control of the National Cancer Institute of Canada and was
      held Apr. 8 to 10, 1994, in Toronto. Participants included experts on control of
      cancer pain and on diffusion techniques, patients with cancer and representatives
      of regulatory agencies. They suggested the following strategies to improve
      outcomes in patients with cancer pain. Processes for accreditation of health care
      institutions should require documentation of cancer pain, its treatment and its
      outcome. Tertiary care facilities that provide cancer treatment should have
      expert, subspecialty, multidisciplinary programs for pain control and should
      provide adequate psychosocial support to patients suffering cancer pain. The
      Canadian Cancer Society should conduct a public-education campaign to encourage
      patients to report pain to health care providers. The National Cancer Institute
      of Canada should foster research on cancer pain by restructuring its process for
      review of pain-research protocols. Examinations for professionals who care for
      patients with cancer should include a defined number of questions concerning pain
      and symptom control. Provincial programs to monitor prescribing through the use
      of triplicate prescription pads should have an educational as well as regulatory
      purpose.

PMID- 7736372
TI  - Periodic health examination, 1995 update: 3. Screening for visual problems among
      elderly patients. Canadian Task Force on the Periodic Health Examination.
AB  - OBJECTIVE: To provide recommendations to family physicians for screening elderly
      patients (over 65 years of age) for visual impairment and its common clinical
      causes. OPTIONS: Visual acuity screening with Snellen sight chart, funduscopy,
      retinal photography, tonometry and perimetry. OUTCOMES: Delay or prevention of
      visual deterioration or blindness. EVIDENCE: A MEDLINE search for relevant
      articles published between January 1986 and December 1993 was undertaken, the
      bibliographies of the articles were scrutinized for additional articles, and
      experts were consulted. The highest available level of evidence was used in
      making recommendations. VALUES: The evidence-based methods and values of the
      Canadian Task Force on the Periodic Health Examination were used. Preservation of
      vision was given the highest value in accordance with other guidelines regarding
      eyesight. BENEFITS, HARMS AND COSTS: Potential benefits are to maintain or
      improve visual acuity. Potential for harm to patients is minimal. Limited data
      are available on costs. RECOMMENDATIONS: There is fair evidence to include in the
      periodic health examination visual acuity testing with a Snellen sight chart and
      funduscopy or retinal photography in elderly patients with diabetes of at least 5
      years' duration (grade B recommendation). The place of funduscopy in the
      detection of age-related macular degeneration and glaucomatous changes is
      controversial. For patients at high risk for glaucoma (positive family history,
      black race, severe myopia or diabetes) it would be prudent to have a periodic
      assessment by an ophthalmologist. VALIDATION: Recommendations differ from those
      of the American Academy of Ophthalmology and the American Optometric Association.
      Recommendations for glaucoma screening are similar to those of the US Preventive
      Services Task Force. Present recommendations have been reviewed by experts in
      ophthalmology and optometry. SPONSOR: These guidelines were developed and
      endorsed by the task force, which is funded by Health Canada and the National
      Health Research and Development Program. The principal author (C.P.) was
      supported in part by the Educational Centre for Aging and Health, McMaster
      University, Hamilton, Ont.

PMID- 7736374
TI  - Toxins and tradition: the impact of food-chain contamination on the Inuit of
      northern Quebec.
AB  - The dependence of Quebec Inuit on their traditional diet, known as "country
      food," is complicated by the presence of toxins in the northern food chain. Dr.
      Eric Dewailly's unexpected finding of high levels of polychlorinated biphenyls
      (PCBs) in Inuit women's breast milk prompted years of research into this
      troubling public health issue. In his recent study of heavy-metal contaminants
      Dewailly found that mercury and organic chlorine compounds such as PCBs were the
      major toxins in Inuit blood samples. Although not present at levels high enough
      to endanger adults, these contaminants may have adverse developmental effects on
      fetuses and breast-fed infants. Although country food is a major source of
      contaminants, it contains important nutrients that counter some of the toxic
      effects. Dewailly's research indicates that the nutritional, economic and
      cultural benefits of country food far outweigh the risks.

PMID- 7736373
TI  - Physician characteristics and prescribing for elderly people in New Brunswick:
      relation to patient outcomes.
AB  - OBJECTIVE: To examine the relation between physician characteristics, prescribing
      behaviour and patient outcomes. DESIGN: Descriptive study linking four provincial
      databases. SETTING: New Brunswick. PARTICIPANTS: All 366 general practitioners
      (GPs) (accounting for 40% of all physicians with a general licence in New
      Brunswick) who ordered at least 200 prescriptions for elderly beneficiaries of
      the New Brunswick Prescription Drug Program and saw at least 20 elderly patients
      in an office setting between Apr. 1, 1990, and Mar. 31, 1991. Physicians with
      palliative care practices were excluded. OUTCOME MEASURES: GPs' personal,
      professional and practice characteristics, their prescribing patterns, and
      mortality, morbidity (number of days in hospital per patient) and hip-fracture
      rates among their elderly patients. RESULTS: Compared with the GPs who had a
      lower mortality rate, those with a higher mortality rate prescribed more drugs
      overall (p < 0.001), specifically antidepressants, bronchodilators, cholesterol
      lowering agents, gastrointestinal drugs, neuroleptics and nonsteroidal anti
      inflammatory drugs (NSAIDs). They also were more likely to be male (p < 0.01),
      had larger practices (p < 0.001), saw more patients per day (p < 0.05) and billed
      more per year (p < 0.001). Compared with the GPs who had a lower morbidity rate,
      those with a higher morbidity rate prescribed more drugs overall (p < 0.005),
      specifically bronchodilators, gastrointestinal drugs and NSAIDs. They also were
      more likely to be younger (p < 0.005) and male (p < 0.01), had fewer years in
      practice (p < 0.001), saw more patients per day (p < 0.05) and billed more per
      patient (p < 0.01). The GPs who had a higher hip-fracture rate prescribed more
      drugs overall (p < 0.001), notably antihypertensives, bronchodilators,
      cholesterol-lowering agents, gastrointestinal drugs and NSAIDs, than those who
      had a lower hip-fracture rate. They also had a larger practice (p < 0.001),
      practised more days per year (p < 0.005), had more patient visits per year (p <
      0.05) and billed more per year (p < 0.001). Younger male GPs who practised with
      relatively more intensity and prescribed more drugs per patient had practices
      with higher morbidity, mortality and hip-fracture rates among their elderly
      patients than the other GPs. CONCLUSIONS: There is a significant relation between
      certain physician characteristics, their prescribing behaviour and patient
      outcomes. Further study is required to determine what physician characteristics
      and prescribing behaviours for specific illnesses contribute to patient outcomes.
      Regional differences should also be examined, as should incentives in this fee
      for-service system. Linkage of these types of provincial databases may help in
      the evaluation of physicians' performance and in the development of strategic
      interventions and practice guidelines.

PMID- 7736375
TI  - Statement on travellers and rabies vaccine.

PMID- 7736376
TI  - The environment was right for Nova Scotia's new environmental health clinic.
AB  - With a $1-million contribution from the Nova Scotia government, Dalhousie
      University medical school is establishing an environmental health clinic that
      will research and treat the controversial condition known as multiple-chemical
      sensitivity. Already several hundred Nova Scotians, including about 100 former
      employees of Halifax's Camp Hill Hospital, have been referred to a part-time
      clinic that addresses environmental illness and other unexplained conditions.
      Some physicians contend that the sensitivity is largely psychosomatic and
      treatments provide little more than a placebo effect, but proponents believe
      research will support environmental health's goal of becoming a new, recognized
      speciality.

PMID- 7736377
TI  - Firearms law raises issue of MDs' duty to predict and report potentially violent
      patients.
AB  - The possibility that an amendment to new firearms legislation would require
      physicians to report potentially violent patients raises the controversial issues
      of physicians' legal duty to warn and the ability of physicians and other health
      care professionals to predict violent behaviour. For these reasons, it will be
      necessary to follow carefully any proposed amendments to the legislation.

PMID- 7736378
TI  - Navigating physician resources on the Internet.
AB  - By providing everything from electronic mail to "virtual patients," computer
      technology and the Internet have made enormous resources available to physicians.
      Science writer Beth Ellenberger gives an overview of the different levels of
      Internet access, as well as the e-mail addresses of some medical resources that
      will be useful to physicians.

PMID- 7736379
TI  - Practical application of air-quality research incorporated in CMHC's research
      house.
AB  - The Canada Mortgage and Housing Corporation has been looking at ways to improve
      indoor air quality since 1984 and now hopes to interest house designers and
      manufacturers in the results of its research. Its flagship project has been the
      construction of a proto-type research house for environmentally hypersensitive
      people.

PMID- 7736380
TI  - Psychopathic patients pose dilemma for physicians and society.
AB  - Psychopaths share chilling personality characteristics that make them extremely
      dangerous and, to date, impossible to cure. The failure to cure or even control
      them has divided the medical and legal communities, as well as society in
      general. What do you do with incurable killers? Lock them up and throw away the
      key, or spend hundreds of thousands of dollars every year to treat them? Some
      experts believe the federal government should commit funds for more research and
      provide special facilities to treat psychopathic patients.

PMID- 7736381
TI  - Breast cancer trials on trial. A case of conflicting ethical interests.

PMID- 7736382
TI  - Is there really an ethical conflict in clinical trials?

PMID- 7736383
TI  - Estimation of currently attainable benefit from mammographic screening of women
      aged 40-49 years.

PMID- 7736384
TI  - p53 expression in patients with cirrhosis with and without hepatocellular
      carcinoma.
AB  - BACKGROUND: Mutated p53 acts as a dominant oncogene, whereas the wild type (wt)
      p53 gene product suppresses cell growth. Abnormalities in the p53 gene are
      reported in more than 50% of malignant tumors. Recently, an allelic loss of
      chromosome 17p, where the p53 gene is located, was found to be more frequent in
      hepatocellular carcinoma (HCC) cell lines and human tumors. In addition, in half
      of the cases of HCC from endemic areas for hepatitis B virus and aflatoxin, a hot
      spot point mutation at codon 249 was detected, as previously reported. Missense
      mutations in p53, mdm-2 complex formation, and other unknown mechanisms may lead
      to stabilization of the gene product, thus rendering it detectable by
      immunohistochemistry. METHODS: To assess the relationship between p53 status at a
      premalignant stage and in HCC, the authors studied the immunohistologic
      expression of p53 in HCC and in the adjacent nontumorous resected liver tissue,
      using monoclonal antibody to wt and mutated p53. RESULTS: Twelve of the 14
      patients with liver tumors had HCC. Of the 12 patients with HCC and underlying
      cirrhosis, 8 (67%) had increased p53 expression in HCC cells. Eight of the 12
      patients with p53-positive HCC cells had p53 overexpression in the nontumorous
      hepatocytes within regenerative nodules adjacent to HCC tissue. Three of 21
      cirrhotic livers without a detectable tumor had increased p53 expression in the
      regenerative nodules. None of the 12 patients with chronic active hepatitis
      without cirrhosis or the 13 with a normal liver histology had increased p53
      expression. CONCLUSION: p53 overexpression in some cirrhotic livers and in
      nontumorous livers of patients with HCC may indicate a normal p53 gene response
      to cellular stress or, alternatively, to an abnormally or mutated p53 gene, and
      could occur before the development of HCC.

PMID- 7736385
TI  - Efficacy of transarterial targeted treatments on survival of patients with
      hepatocellular carcinoma. An Italian experience.
AB  - BACKGROUND: Most patients with hepatocellular carcinoma (HCC) are not suitable
      for surgical therapy. Systemic chemotherapy, immunotherapy, and hormonotherapy
      have not had convincingly acceptable results. Therefore, transarterial catheter
      targeted therapies such as intraarterial chemotherapy (IAC), possibly followed by
      transcatheter arterial chemoembolization (TACE), have been proposed. METHODS: A
      survival analysis curve was drawn using the Kaplan-Meier method for 164 patients,
      100 with HCC who underwent TACE (69) or IAC (31), and a matched historic group of
      64 who did not receive specific antineoplastic treatment. RESULTS: A
      significantly more favorable survival was observed for TACE-treated patients
      compared with IAC-treated patients (P < 0.001); TACE- and IAC-treated patients
      had a statistically superior survival than that of untreated patients (P < 0.001
      and P < 0.025, respectively). This difference was still significant (P < 0.001)
      when the patients were subdivided into Classes A and B and Stages I and II
      following Child's and Okuda's criteria. The TACE- and IAC-treated groups had a
      good relationship between technical efficacy of therapy and survival. Stratifying
      the patients according to the degree of iodized oil (Lipiodol Ultrafluid,
      Guerbet, Aulnay-Sous-Bois, France) uptake in the three groups with Group 1 having
      an uptake greater than 75% of tumor mass, Group 2 having an uptake of 50%-75%,
      and Group 3 having an uptake less than 50%, survival at 6, 12, 24, 36, and 48
      months was calculated as 94%, 88%, 67%, 53%, and 30%, respectively, for Group 1;
      86%, 68%, 13%, 13%, and 0% for Group 2, and 43%, 23%, 6%, 6%, and 0% for Group 3
      (Group 1 vs. Group 2: P < 0.001; Group 1 vs. Group 3: P < 0.001; Group 2 vs.
      Group 3: P < 0.001, respectively). The most important side effects after the
      intraarterial procedure were fever (46.2%), abdominal pain (36.6%), chemical
      cholecystitis (8%), and pancreatitis (1.7%). Death strictly related to treatment
      occurred in two patients; one had massive bleeding due to ruptured esophageal
      varices, and the other had a subphrenic abscess of a superficial HCC of the VIII
      segment. CONCLUSIONS: Transcatheter arterial chemoembolization and IAC were
      effective and relatively safe, and the authors believe that they have a primary
      role in treating patients with unresectable HCC larger than 5 cm; iodized oil
      uptake can be considered a suitable prognostic marker.

PMID- 7736386
TI  - Hepatic arterial infusion of recombinant platelet factor-4 suppresses metastases
      to the lungs from tumors implanted into the livers of rabbits.
AB  - BACKGROUND: This study evaluated the toxicity (Part I) and antitumor effects
      (Part II) associated with hepatic arterial infusion of recombinant platelet
      factor-4 (rPF4), an antiangiogenic protein. METHODS: Healthy rabbits (Part I) and
      rabbits with tumors implanted in their livers (Part II) received saline or rPF4
      via hepatic arterial infusion. Three saline-receiving and four rPF4-receiving
      animals died 2-3 days postinfusion from gastroduodenal thromboembolism. The
      remaining animals were necropsied 3, 7, 10, or 14 days postinfusion. Blood
      analyses and hepatic angiography were performed before infusion and at the time
      of sacrifice. RESULTS: In Part I, focal coagulation necrosis of the hepatic
      parenchyma was observed in 1 of 11 rabbits that received saline and in 6 of 10
      that received rPF4. In Part II, hepatic arterial infusion of rPF4 had no effect
      on growth of the implanted liver tumors. However, the protein significantly
      reduced the incidence of lung metastasis. CONCLUSIONS: Intraarterial infusion of
      rPF4 significantly reduced the incidence of lung metastasis. Nonheparin systemic
      anticoagulation may be needed during catheterization and infusion procedures to
      prevent thromboemboli.

PMID- 7736387
TI  - Secretion of atrial natriuretic peptide and vasopressin by small cell lung
      cancer.
AB  - BACKGROUND: Hyponatremia in patients with small cell lung cancer (SCLC) is a
      common clinical problem usually attributed to tumor secretion of arginine
      vasopressin (AVP). It recently was shown that some SCLC cell lines produce atrial
      natriuretic peptide (ANP). The purpose of this investigation was to determine the
      frequency and clinical consequences of secretion of ANP by SCLC and the relative
      contribution of ANP and AVP to the hyponatremia associated with this disease.
      METHODS: Levels of ANP and AVP were measured in 23 SCLC cell lines and 23 other
      human tumor cell lines. Also, ANP and AVP levels were determined in plasma
      samples from 69 patients with active small cell carcinomas. RESULTS: Of the 23
      SCLC lines, 16 (70%) had elevated ANP levels. Only two (8.7%) had elevated AVP
      levels, and these two also had elevated ANP levels. One of the ANP-producing cell
      lines was derived from a hyponatremic patient with no other apparent explanation
      for a low sodium level. However, the four cell lines with the highest levels of
      ANP were derived from patients who were not hyponatremic. Two other human tumor
      lines also produced ANP. Of the 69 patients with SCLC, 21 (30.4%) had elevated
      ANP levels, whereas 4 (6%) had elevated AVP levels. Fifteen of these patients
      were hyponatremic during their clinical course (21.7%). Of the eight patients who
      were hyponatremic when samples were collected, two had elevated ANP levels, and
      only one had elevated AVP levels. Six patients (8.7%) had symptoms of postural
      hypotension, possibly attributable in some cases of tumor secretion of ANP.
      CONCLUSIONS: The majority of SCLC lines produce ANP, and a minority produce AVP.
      Secretion of ANP may result in hyponatremia and/or postural hypotension. However,
      secretion of either or both of these peptides does not account for all cases of
      hyponatremia in patients with SCLC and does not necessarily cause clinical
      manifestations.

PMID- 7736389
TI  - Flow cytometric analysis of the DNA content of adenocarcinoma of the lung,
      especially for patients with stage 1 disease with long term follow-up.
AB  - BACKGROUND: To assess the prognostic value of DNA ploidy in adenocarcinoma of the
      lung, the authors performed a flow cytometric study using paraffin embedded
      archival material from 160 patients (109 [68%] with aneuploid lesions, 51 [32%]
      with diploid lesions) who underwent surgical resection from 1982 to 1991.
      METHODS: The proportion of DNA aneuploid tumors increased as the disease stage
      advanced, from 35 of 63 (55.5%) with Stage 1 disease to 15 of 20 (75.0%) with
      Stage 2 disease, to 40 of 53 (75.5%) with Stage 3a disease, to 19 of 24 (79.2%)
      with Stage 3b disease. However, this trend was not statistically significant.
      Comparison of the survival time of the 160 patients with adenocarcinoma of the
      lung with a median follow-up of 7.8 years revealed that patients with diploid
      tumors had significantly longer survival than did those with aneuploid tumors (P
      < 0.01). RESULTS: Examination by stage showed that patients with Stage 1 disease
      with diploid tumors had significantly longer survival times than did those with
      aneuploid tumors (P < 0.05) but that there were no significant differences in
      clinical outcome in patients with Stage 2, 3a, and 3b diploid tumors.
      CONCLUSIONS: Analysis of aneuploid versus diploid DNA content in patients with
      Stage 1 adenocarcinoma of the lung is concluded to be useful in evaluating
      clinical outcome and prognosis.

PMID- 7736388
TI  - Patterns of cigarette sales and lung cancer mortality in some central and eastern
      European countries, 1960-1989.
AB  - BACKGROUND: Remarkable increases in lung cancer risk recently have been observed
      in the Central and Eastern European (CEE) area. This study examines the patterns
      of lung cancer mortality rates and cigarette sales in 1960-1989 in seven CEE
      countries with a total population of 97.5 million and 43,000 deaths from lung
      cancer in the last year under study. METHODS: Trends in cigarette sales and
      mortality rates from lung cancer in seven CEE countries were compared for the
      years 1960-1989. RESULTS: Among males, recent lung cancer death rates were the
      highest in Europe, and trends by country largely reflected the varied prevalence
      and duration of smoking in previous decades. For females, lung cancer mortality
      rates were much lower, although there were exponential rate increases. In the
      more recent birth cohorts, there were some declines in mortality rates among
      males, but not among females. CONCLUSIONS: The rising cigarette consumption
      through the 1960s, 1970s, and, in some countries, the 1980s is accompanied in
      most of the countries by rising lung cancer mortality rates for young adults.
      This increasing cigarette consumption will determine future trends in lung
      cancer, which will increase well beyond the turn of the century and will continue
      longer for females than for males. This outlook underlines the urgent need for
      comprehensive lung cancer prevention with the concerted control of smoking as a
      priority. The role of cofactors and their interaction with smoking deserve
      further exploration.

PMID- 7736390
TI  - Parosteal osteoma of bones other than of the skull and face.
AB  - BACKGROUND: Osteoma of the skull and facial bones is not uncommon, is usually
      asymptomatic, and may be associated with Gardner's syndrome. Osteomas involving
      other bones are unusual. METHODS: The authors describe 14 cases (eight men and
      six women from age 21-66 years) of parosteal osteoma of bones other than of the
      skull and face. RESULTS: Thirteen lesions involved long bones, and one involved
      the clavicle. A long-standing (18 months to 31 years) mass was reported in seven
      patients. Symptoms of pain, a mass, or both were present in all except three
      patients who were asymptomatic. Lesions ranged from 2.5 to 20 cm in greatest
      dimension. Histologically, they blended with the cortex, did not infiltrate the
      medullary cavity, and consisted of dense sclerotic lamellar bone with haversian
      systems, similar to the architecture of normal cortical bone. There was no
      spindle cell proliferation. Nine patients underwent resection, four had biopsy,
      and one had debulking. With a follow-up of 1-23 years, no recurrence or
      metastasis was reported. CONCLUSIONS: Parosteal osteoma must be distinguished
      from parosteal osteosarcoma, a low grade malignant neoplasm. If radiographs do
      not identify areas of radiolucency and sections do not contain spindle cells, the
      diagnosis of parosteal osteoma is justified.

PMID- 7736391
TI  - Acute agranular CD4-positive natural killer cell leukemia. Comprehensive
      clinicopathologic studies including virologic and in vitro culture with inducing
      agents.
AB  - BACKGROUND: A 63-year-old male presented with fever, a subcutaneous nodule,
      gingival hypertrophy, lacrimal gland enlargement, and no lymphadenopathy or
      hepatosplenomegaly, but had anemia, thrombocytopenia, and peripheral blood (PB)
      plus bone marrow (BM) involvement by leukemic cells. There was minimal response
      to multiagent chemotherapy and local radiotherapy, with a survival of 6.5 months
      from disease diagnosis. METHODS: The PB and/or BM leukemic cells were evaluated
      using electron microscopy (EM), immunohistochemistry, flow-cytometric
      immunophenotyping, cytochemistry, cytogenetics, Southern blot analysis for gene
      rearrangement and Epstein-Barr virus (EBV), polymerase chain reaction for EBV and
      human herpes virus-6 (HHV-6), and in vitro culturing with inducing agents.
      RESULTS: The leukemic cells were agranular and monocytoid, with a hairy cell-like
      bone marrow biopsy infiltrate. Myeloperoxidase (MPO) and alpha-naphthyl butyrate
      esterase staining was negative, and periodic acid-Schiff staining was positive by
      light microscopy. Electron microscopy showed MPO negativity and a lack of
      parallel tubular arrays. The immunophenotype was CD3-, CD56+, CD4+, CD8-, CD15+,
      TCR1-, and TCR2-, with germline immunoglobulin and T-cell receptor genes and an
      abnormal karyotype (44XY, 5q-, -13, 13q+, -15). No genomic material for EBV or
      HHV-6 was detected. Cell cultures with butyrate and N,N-hexamethylene bis
      acetamide suggested the possible induction of tumor cells to express a T-cell
      immunophenotype. CONCLUSION: A case of clonal acute natural killer (NK) cell
      leukemia with an unusual morphology (agranular) and unique phenotype (CD3-,
      CD56+, CD4+, CD15+) is presented. Unlike as in other acute NK leukemias, EBV was
      negative; there was no evidence of HHV-6. The tumor cell, after culturing with
      differentiating agents, may have been induced to express a T-cell
      immunophenotype.

PMID- 7736392
TI  - Primary cutaneous melanoma. Identification of prognostic groups and estimation of
      individual prognosis for 5093 patients.
AB  - BACKGROUND: Numerous investigations have examined prognostic factors for patients
      with primary cutaneous melanoma. However, only a few studies have been published
      on the definition of prognostic groups. The first aim of the present study was to
      determine the relative importance of different prognostic factors in a large
      collective study. The second aim was to define prognostic groups of patients
      based on combinations of prognostic factors and to define a model that allows the
      estimation of individual survival probability. METHODS: Long term follow-up of
      5264 patients with invasive primary cutaneous melanoma was performed from 1970 to
      1988 at four German University Departments of Dermatology (Berlin-Steglitz,
      Munster-Hornheide, Tubingen, and Wurzburg). The multivariate Cox model was used
      to analyze 5093 patients, and 4371 patients with complete information were
      included in a classification and regression tree analysis (CART). RESULTS: Tumor
      thickness, sex, anatomic location, and level of invasion were highly significant
      prognostic factors according to the multivariate analysis (P < 0.0001). However,
      histologic subtype and age influenced prognosis less significantly (P < 0.05).
      The CART analysis resulted in 12 groups defined mainly by tumor thickness, sex,
      and anatomic location, which were combined into five prognostic groups. The
      prognostic stratification defined by the five groups was superior compared with
      the standard TNM model. Ten-year survival rates of the five groups ranged from
      97% to 14% (P < 0.0001), and an equation was used to calculate individual
      survival probabilities based on the significant factors of the Cox model.
      CONCLUSIONS: Consideration of all significant prognostic factors of patients with
      primary cutaneous melanoma investigated in the present study allows for the
      definition of prognostic groups with a more reliable estimation of prognosis than
      by previous staging systems and also enables calculation of individual survival
      probabilities.

PMID- 7736393
TI  - Primary cutaneous melanoma. Prognostic classification of anatomic location.
AB  - BACKGROUND: Anatomic location has been identified by several investigators as a
      significant prognostic factor for patients with primary cutaneous melanoma (CM).
      However, the best determination of higher and lower risk sites is still
      controversial, and the biologic significance of tumor site in the course of
      primary CM is unknown. The aim of the present study was to identify higher and
      lower risk sites based on multivariate analysis. METHODS: A series of 5093
      patients with invasive primary cutaneous melanoma followed from 1970 to 1988 at
      four university centers in Germany was investigated using the multivariate Cox
      proportional hazard model to analyze the importance of anatomic location for
      survival probability. RESULTS: The anatomic location was found to be a highly
      significant prognostic factor for patients with primary melanoma by multivariate
      analysis (P < 0.0001). An optimized classification into sites of higher and lower
      risk with respect to survival was evaluated by multivariate analysis controlling
      for the possible confounding effects of the other significant prognostic factors.
      Relative to the lower leg as the prognostically favorable baseline, the following
      locations were associated with a significantly higher risk of death caused by
      primary cutaneous melanoma: back and breast (thorax), upper arm, neck, and scalp
      (TANS regions). The lower trunk, thigh, lower leg, foot, lower arms, hands, and
      face were identified as lower risk sites. CONCLUSIONS: Anatomic location was
      confirmed as an independent prognostic factor for patients with primary cutaneous
      melanoma. The TANS regions were identified as high risk sites, and the lower
      trunk, thigh, lower leg, foot, lower arms, hands, and face were identified as
      intermediate sites.

PMID- 7736394
TI  - Primary cutaneous melanoma. Optimized cutoff points of tumor thickness and
      importance of Clark's level for prognostic classification.
AB  - BACKGROUND: Maximum tumor thickness and level of invasion are known to be the
      most important prognostic factors for patients with primary cutaneous melanoma.
      However, the classification of tumor thickness and the question of whether the
      combination of tumor thickness and level of invasion provides a better prognostic
      classification than tumor thickness alone are still matters of debate. The
      present study examined the relationship between tumor thickness and survival
      probability to define cutoff points of tumor thickness. Secondly, it investigated
      the prognostic value of the combination of tumor thickness and level of invasion
      as proposed in the current TNM classification system. METHODS: A series of 5093
      patients with invasive primary cutaneous melanoma followed from 1970 to 1988 at
      four University centers in Germany (Departments of Dermatology in Tubingen,
      Wurzburg, Berlin-Steglitz, and at the Fachklinik) were analyzed by multivariate
      Cox models. RESULTS: The relationship between tumor thickness and relative risk
      of death caused by melanoma was found to be almost linear to a tumor thickness of
      6 mm. For tumors greater than 6 mm, no further marked increase in relative risk
      was observed. The stratification of tumor thickness with endpoints at 1, 2, and 4
      mm resulted in the best fit to the authors' data among all classifications with
      three endpoints, but differences were only slight. By multivariate analysis, the
      combination of tumor thickness and level of invasion as proposed by the current
      TNM classification were found to be prognostically less significant than tumor
      thickness alone. The prognostic influence of level of invasion was proved
      statistically only for tumor thickness less than or equal to 1 mm. CONCLUSIONS:
      The proposed stratification of tumor thickness with cutoff points at 1, 2, and 4
      mm was supported by multivariate statistical analysis. The analysis of the
      current TNM staging system indicates the precedence of tumor thickness for the
      staging of patients with primary cutaneous melanoma in the case of discordance
      between tumor thickness and level of invasion.

PMID- 7736395
TI  - Efficacy of breast cancer screening by age. New results from the Swedish Two
      County Trial.
AB  - BACKGROUND: Several studies have found a smaller effect of breast cancer
      screening on breast cancer mortality in women aged younger than 50 years compared
      with older women. Various possible reasons have been suggested for this, but none
      firmly is established. METHODS: The Swedish Two-County Study is a randomized
      trial of breast cancer screening of women aged 40-74 years, comprising with
      133,065 women with a 13-year follow-up of 2467 cancers. The Breast Cancer
      Detection Demonstration Project (BCDDP) is a nonrandomized screening program in
      the United States, with a 14-year follow-up of 3778 cancers in women aged 40-74
      years. The Swedish results by age were updated. The lesser effect of screening at
      ages 40-49 years was investigated in terms of sojourn time (the duration of the
      preclinical but detectable phase) size, lymph node status, and histologic type of
      the tumors diagnosed in the Swedish Study and their subsequent effect on survival
      using survival data from both studies. RESULTS: In the Swedish Trial, a 30%
      reduction in mortality associated with the invitation to screening of women aged
      40-74 years was maintained after 13-years of follow-up. The reduction was 34% for
      women aged 50-74 years and 13% for women aged 40-49 years. Results indicated that
      the reduced effect on mortality for women aged 40-49 years was due to a
      differential effect of screening on the prognostic factors of tumor size, lymph
      node status, and histologic type. The mean sojourn times in the age groups 40-49
      years, 50-59 years, 60-69 years, and 70-74 years were 1.7, 3.3, 3.8, and 2.6
      years, respectively. CONCLUSIONS: These results suggest that much, although not
      all, of the smaller effect of screening on mortality in women aged 40-49 years is
      due to faster progression of a substantial proportion of tumors in this age group
      and the rapid increase in incidence during this decade of life. It is concluded
      that the interval between screenings should be shortened to achieve a greater
      benefit in this age group. It is estimated that a 19% reduction in mortality
      would result from an annual screening regime.

PMID- 7736396
TI  - Clinical significance of intratumoral blood flow in cervical carcinoma assessed
      by color Doppler ultrasound.
AB  - BACKGROUND: Much evidence has suggested that vascular density reflects the
      clinical behavior of cancer. In this study, the intratumoral blood flow in
      cervical carcinomas was assessed by transvaginal color Doppler ultrasound, and
      its clinical significance was evaluated. METHODS: Sixty-five patients with Stage
      Ib-IIb cervical carcinoma exhibiting visible cervical tumor by transvaginal
      ultrasound were enrolled. All patients were scheduled for radical hysterectomy
      and pelvic lymph node dissection. Transvaginal color Doppler ultrasound was
      performed before surgery to search for blood flow signals from the tumor and the
      main uterine artery. The corresponding arterial resistance index (RI) was
      calculated. Clinical and pathologic data were recorded. A cytokinetic study was
      performed by propidium iodide staining and flow cytometry. The human
      papillomavirus (HPV) status was assessed by polymerase chain reaction. RESULTS:
      Intratumoral blood flow was detected by color Doppler ultrasound in 46.2% (30/65)
      of the tumors. Patients with detectable intratumoral blood flow exhibited
      significantly more pelvic lymph node metastasis (10/30 vs. 2/35, P = 0.005), a
      higher percentage of cancer cells in the S- + G2M-phase (30.02 +/- 18.54% vs.
      19.35 +/- 11.21%, P < 0.005), and a higher prevalence of HPV infection (30/30 vs.
      25/35, P = 0.001) when compared with those without intratumoral blood flow. No
      significant difference was observed concerning the patient's age, tumor size,
      clinical staging, histologic type, and DNA ploidy status between these two
      groups. Regression analysis of the intratumoral RI value on the S- + G2M-phase
      fraction showed linear regression (n = 30, r2 = 0.501, P < 0.01). The RI values
      of the main uterine artery showed no significant difference between these two
      groups. CONCLUSION: The intratumoral blood flow by transvaginal color Doppler
      ultrasound correlated well with a higher proliferation index, higher incidence of
      HPV infection, and pelvic lymph node metastasis in cervical carcinoma.

PMID- 7736397
TI  - Altered expression of nm23-H1 and c-erbB-2 proteins have prognostic significance
      in adenocarcinoma but not in squamous cell carcinoma of the uterine cervix.
AB  - BACKGROUND: The reduced expression of nm23-H1 protein and/or overexpression of c
      erbB-2 protein reportedly is associated with a high incidence of lymphatic
      metastasis or poor prognosis of the patient in a variety of human malignant
      tumors. METHODS: The expression patterns of nm23-H1 and c-erbB-2 proteins were
      analyzed by immunohistochemical staining using formalin fixed, paraffin embedded
      sections of 88 cases of invasive carcinoma (39 matched pairs of adenocarcinoma
      and squamous cell carcinoma, 8 cases of adenosquamous carcinoma, and 2 cases of
      undifferentiated carcinoma) and 31 cases of preinvasive lesions of the uterine
      cervix. RESULTS: Expression of nm23-H1 was detected in 46% of adenocarcinoma and
      in 36% of squamous cell carcinoma of the uterine cervix, whereas c-erbB-2
      expression was evident in 49% and 38%, respectively. Negative expression of nm23
      H1, positive expression of c-erbB-2, and a combined nm23-H1-negative and c-erbB-2
      positive expression were associated with a high incidence of lymph node
      involvement (P = 0.36, P = 0.0015, P = 0.0055, respectively) and with poor
      prognosis of patients (P = 0.034, P = 0.014, P = 0.00008, respectively) with
      adenocarcinoma of the uterine cervix, but not in those with squamous cell
      carcinoma. Multivariate analysis using the Cox's proportional hazard model also
      revealed that these three factors significantly contributed to the prognosis of
      patients with cervical adenocarcinoma. CONCLUSIONS: Reduced expression of the
      nm23-H1 protein, increased expression of the c-erbB-2 protein, and a combined
      nm23-H1-negative and c-erbB-2-positive expression have prognostic significance in
      patients with adenocarcinoma, whereas they may not be associated with the
      prognosis of squamous cell carcinoma of the uterine cervix, nm23-H1 and c-erbB-2
      proteins may have different functions according to the subtype of cervical
      carcinoma.

PMID- 7736398
TI  - Age, substance abuse, and survival of patients with cervical carcinoma.
AB  - BACKGROUND: The poor survival of young patients with cervical cancer in a low
      income, disadvantaged community stimulated an investigation of pathologic and
      behavioral risk factors. METHODS: The records of 1173 patients with cervical
      cancer diagnosed in 1967-1988 were evaluated with respect to age, stage,
      histology, and presenting symptoms. Histopathologic risk factors were evaluated
      in 196 patients with Stage IB disease treated by initial hysterectomy. Substance
      abuse behaviors were evaluated for 332 symptomatic patients with Stages IB-III
      disease diagnosed from 1976 to 1988. RESULTS: There were no significant age
      related differences in survival for patients without squamous cell carcinoma or
      those with Stage IA and asymptomatic Stage IB squamous cell carcinoma. Women age
      70 years and older had a poorer survival rate than did younger women with Stages
      IB-III disease. Symptomatic patients with squamous cell carcinoma younger than
      age 50 years had a poorer survival than did patients age 50-69 years with Stages
      IB/IIA, IIB, and III disease. For patients with symptomatic Stage IB tumors, poor
      prognostic histopathologic factors were distributed equally among women younger
      than age 50 and those aged 50-69 years. Substance abuse was significantly more
      prevalent among younger patients, and patients who smoked or abused alcohol or
      drugs had significantly poorer survival than did nonsubstance abusers. However,
      in a multivariate analysis of age, stage, and substance abuse, young age remained
      a significantly poor prognostic factor. CONCLUSIONS: Substance abuse may
      contribute to poor outcome of young patients with symptomatic squamous cell
      carcinoma but does not explain adequately their poor survival.

PMID- 7736399
TI  - Aberrant pattern of lectin binding in low and high grade prostatic
      intraepithelial neoplasia.
AB  - BACKGROUND: High grade prostatic intraepithelial neoplasia (PIN) is considered a
      precursor lesion for peripheral prostatic adenocarcinoma. The biologic
      significance of low grade PIN is unknown; however, the likelihood of progression
      from low to high grade PIN has been suggested. METHODS: A battery of nine lectins
      was applied to paraffin sections from 20 prostatectomies to identify prostatic
      carcinoma. The patterns of lectin binding were compared among
      normal/hyperplastic, dysplastic, and malignant glands. The increase in the Ki-67
      defined growth fraction was compared with the lectin binding pattern. RESULTS: An
      aberrant lectin binding pattern, similar to that observed in adenocarcinoma, was
      observed in PIN for four of the lectins; this distinct staining pattern was found
      in glands with minimal dysplastic changes and in glands with high grade
      dysplasia. Specifically, staining for soy bean agglutinin and Ulex europaeus
      agglutinin was negative in benign and hyperplastic glands and positive in
      dysplastic glands and carcinoma. Staining for wheat germ agglutinin and peanut
      agglutinin was weakly positive or negative in normal and hyperplastic glands,
      whereas it was strongly positive in dysplasia and carcinoma. The staining for
      Concavalin A, Ricinus communis agglutinin, Dolichos biflorus agglutinin, and Lens
      culinaris agglutinin showed no difference between normal/hyperplastic and
      dysplastic glands. The aberrant lectin binding already was evident in low grade
      dysplasia versus the increased Ki-67 defined-growth fraction that was obvious
      only in high grade dysplasia and carcinoma. CONCLUSIONS: These findings suggest
      that the early dysplastic lesions in the prostate may be part of a continuum in
      the multistep process leading to invasive carcinoma.

PMID- 7736400
TI  - The epidemiology of renal cell carcinoma. A second look.
AB  - BACKGROUND: From 1973 to 1991, the incidence of kidney cancer in the United
      States increased by 35.4%. METHODS: A multicenter, hospital-based case-control
      study was conducted from 1977 to 1993 through an interview of 788 patients with
      renal cell carcinoma and 779 control subjects. RESULTS: Compared with those who
      never smoked, the odds ratio (OR) for renal cell carcinoma among current
      cigarette smokers was 1.4 (95% confidence interval [CI] 1.02-2.0) for men and 1.1
      (95% CI 0.7-1.6) for women. Among men, there was a rising trend in the odds
      ratios with increasing pack-years of smoking (P < 0.01) but not with the number
      of cigarettes smoked per day. The OR among those currently smoking nonfilter
      cigarettes exclusively was 2.4 (95% CI 1.2-4.9) for men and 2.0 (95% CI 0.4-11.1)
      for women. No increased risk was observed among current smokers of filter
      cigarettes. Among men, the OR associated with chewing tobacco was 3.2 (95% CI 1.1
      8.7). Total alcohol consumption was unrelated to the risk of renal cell
      carcinoma. A joint effect was observed among subjects with a high body mass index
      who reported a history of hypertension (OR = 1.9, 95% CI 1.01-3.5) for men and
      3.2 (95% CI 1.3-7.7) for women. CONCLUSION: High body weight and hypertension
      were related jointly to renal cell carcinoma. Smoking nonfilter cigarettes and
      long term cigarette smoking (> or = 30 years) was a predictor for renal cell
      carcinoma risk in men. No significant association was found between smoking and
      renal cell carcinoma in women.

PMID- 7736401
TI  - Steroid-responsive interstitial lung disease in patients receiving 2'-deoxy-5
      fluorouridine-infusion chemotherapy. A report of three cases.
AB  - BACKGROUND: Continuous infusion of 2'-deoxy-5-fluorouridine (FUdR) has shown
      promise in its activity against metastatic renal cell carcinoma. Its side-effect
      profile is dominated by gastrointestinal toxicity; there are no known adverse
      pulmonary reactions. To the authors' knowledge, this is the first report on the
      development of lung toxicity in three patients receiving FUdR-infusion
      chemotherapy for metastatic renal cell carcinoma. METHODS: The hospital charts of
      three patients presenting with pulmonary symptoms during FUdR chemotherapy were
      reviewed. A literature search was performed regarding FUdR-related pulmonary
      toxicity. RESULTS: Nonproductive cough, dyspnea, and fever appeared within the
      10th chemotherapy cycle. Chest radiographs showed interstitial disease in each
      case, accompanied by a restrictive pattern by pulmonary-function testing. Lung
      biopsies were performed on two patients showing a pattern of interstitial
      inflammation. Discontinuing FUdR and instituting steroidal therapy invariably
      improved symptoms, as was evident by chest radiographs and pulmonary function
      tests. In one patient, resuming FUdR treatment resulted in a recurrence of the
      respiratory symptoms, which was controlled with an increased steroidal dose. All
      three patients required low dose steroids to maintain their baseline respiratory
      functions. CONCLUSIONS: 2'-deoxy-5-fluorouridine-related lung toxicity is an
      uncommon event and occurs late in the treatment course. It is rapidly symptomatic
      and responds readily to steroidal therapy.

PMID- 7736402
TI  - Expression of transforming growth factor-beta 1 in human bladder cancer.
AB  - BACKGROUND: Elevated expression of transforming growth factor-beta 1 (TGF-beta 1)
      has been reported in several types of human cancer. However, the significance of
      TGF-beta 1 expression in clinical bladder cancer is not well known. METHODS: The
      levels of TGF-beta 1 expression were quantitated using a polymerase chain
      reaction-based method in tissue specimens obtained from 51 patients with bladder
      cancer. RESULTS: Transforming growth factor-beta 1 expression in bladder cancer
      was higher than that found in normal bladder epithelium (P < 0.01). Significantly
      higher levels of TGF-beta 1 transcripts were observed in low and intermediate
      grade (Grade 1 and 2) tumors than in high grade (Grade 3) tumors (P < 0.02).
      Superficial (pTa and pT1) tumors had higher levels of TGF-beta 1 than invasive
      (pT2 or higher) tumors (P < 0.05). CONCLUSIONS: These results suggest that
      enhanced expression of TGF-beta 1 is specific to low grade and stage bladder
      cancer. Transforming growth factor-beta 1 may play an important role in the early
      stages of human bladder cancer development, and TGF-beta 1 expression could
      provide a new relevant tumor marker for determining tumor progression in patients
      with bladder cancer.

PMID- 7736403
TI  - Immunohistochemical expression of the estrogen receptor-related antigen (ER-D5)
      in human intracranial tumors.
AB  - BACKGROUND: Expression of the estrogen receptor-related antigen (ER-D5) has been
      reported in some normal and neoplastic tissues. The authors evaluated the
      expression of ER-D5 in 143 intracranial tumors of different histologic types.
      METHODS: Formalin fixed, paraffin embedded tumor sections were stained with the
      monoclonal D5 antibody by avidin-biotin complex immunohistochemistry. RESULTS:
      Eighty-eight (62%) of the 143 brain tumors showed positive ER-D5
      immunoreactivity. ER-D5 expression was observed in 9/30 low grade astrocytomas,
      in 6/13 anaplastic astrocytomas, in 16/27 glioblastomas, in 2/5 ependymomas, in
      5/8 medulloblastomas, in 10/15 meningiomas, in 20/23 schwannomas, in 11/11
      hemangioblastomas, in 9/9 germ cell tumors, in 0/2 oligodendrogliomas, and in
      17/28 pediatric and childhood brain tumors. The mean percentage of ER-D5-positive
      cells varied in different tumor types, was lowest in the meningotheliomatous
      meningiomas, and was highest in the hemangioblastomas. ER-D5 immunoreactivity was
      also observed in the microvascular endothelial proliferations and in tumor blood
      vessels. ER-D5 expression in tumors was not related to the overall tumor grades,
      but a statistically significant higher percentage of ER-D5-positive cells was
      noted in the glioblastomas compared with the low grade astrocytomas (P < 0.05)
      and in the combined high grade tumors compared with the low grade tumors (P <
      0.005) if vascular-origin tumor hemangioblastomas are considered a separate
      entity from other brain tumors. CONCLUSION: The current study suggests that the
      ER-D5 antigen may participate in the growth of the intracranial tumors and tumor
      angiogenesis. ER-D5 in embryonal and germ cell brain tumors suggests that ER-D5
      may be a developmentally regulated protein.

PMID- 7736404
TI  - Cost effectiveness and outcome assessment of magnetic resonance imaging in
      diagnosing cord compression.
AB  - BACKGROUND: This study was designed to investigate the costs associated with the
      use of magnetic resonance imaging (MRI) in the workup of spinal cord compression
      caused by metastatic disease, an area in which it has proven to be diagnostically
      useful. METHODS: The study was divided into two parts. Part 1 consisted of a
      retrospective review of the hospital charts of 46 patients, half of whom were
      diagnosed with cord compression in the pre-MRI era and the other half diagnosed
      after MRI availability; costs for these two groups were compared. Part 2
      consisted of a review of several major studies comparing the sensitivities and
      specificities of MRI with alternative imaging techniques, usually myelography.
      Cost effectiveness and cost/cost ratios were derived for diagnostic usefulness
      using prevalence, sensitivity, specificity, and cost estimates of MRI and its
      alternatives, including costs of false-negative and false-positive testing.
      RESULTS: Our hospital-based experience yielded an average cost of $ 3664 per
      patient without MRI and $ 2283 per patient when MRI was available (1991 dollar
      amounts). The cost of diagnosis was 65% more expensive without MRI. Use of the
      literature-based experience demonstrated that the cost of diagnosis was at least
      82% more costly without MRI than when it was available. However, when key
      variables were altered during sensitivity analysis, this difference of increased
      cost of diagnosis without MRI ranged from 25% to 98%. CONCLUSION: This work
      suggests that MRI may result in significant economic benefits in diagnosing
      metastatic cord compression, but further work is needed on physician behavior and
      referral patterns with MRI versus myelography as is long term follow-up for
      potential reductions in patient debility using MRI.

PMID- 7736405
TI  - Adrenocortical carcinoma. A clinical study and treatment results of 52 patients.
AB  - BACKGROUND: Adrenocortical carcinoma is a rare tumor with a poor prognosis. This
      work was aimed at analyzing the clinical outlook and treatment results of 52
      patients with this disease. METHODS: This study included patients with
      adrenocortical carcinoma referred to the Department of Endocrinology at the
      Center of Postgraduate Medical Education (Warsaw, Poland) during the last 30
      years. In 11 patients, the adrenal tumor was found incidentally by
      ultrasonographic scan. Hormonal examinations made it possible to define the
      endocrine activity of the tumors, whereas imaging techniques helped to determine
      their staging. Forty-eight patients underwent surgery, and 36 of them received
      mitotane. This drug was administered to 26 patients for a range of 10 months to
      10 years; 13 patients received mitotane immediately after the operation, and 13
      others after a delay. The patients with severe hypercorticism were pretreated
      before surgery with aminoglutethimide and mitotane. RESULTS: The study comprised
      10 men and 42 women; hormonally active tumors were diagnosed in 39 of them.
      Cushing's syndrome was the most frequent entity. At diagnosis, 17 cases were
      classified as localized disease, 15 as regional disease, and 20 as distant
      disease. Pretreatment with the inhibitors of steroidogenesis improved the
      survival perspectives in the early postoperative period. As of this writing,
      there were 12 survivors in the group of 26 patients treated by surgery and long
      term mitotane therapy and only 2 survivors of 7 patients treated with surgery
      only. CONCLUSIONS: Surgery with immediate adjuvant long term mitotane
      administration was the most effective form of therapy for patients with
      adrenocortical carcinoma.

PMID- 7736406
TI  - Reversible hepatic steatosis in patients treated with interferon alfa-2a and 5
      fluorouracil.
AB  - BACKGROUND: Thirty previously untreated patients with metastatic colorectal
      carcinoma were randomized as part of two multicenter Phase III trials. Twenty-two
      patients were randomized to receive either 5-fluorouracil (5-FU)/interferon alfa
      2A (IFN-alpha) or 5-FU/leucovorin (11 patients in each arm). Eight patients were
      randomized to receive 5-FU/IFN-alpha or 5-FU alone (4 patients in each arm).
      METHODS: Twenty-three patients (13 patients treated with 5-FU/IFN-alpha and 10
      patients treated with 5-FU/leucovorin or 5-FU alone) were evaluated regularly for
      response by computed tomography (CT) scans of the abdomen when treatment began
      and then every 6-8 weeks. RESULTS: Incidentally, four patients developed hepatic
      steatosis during treatment with IFN-alpha and 5-FU. The diagnosis was based on a
      decreased CT value of the liver parenchyma by repeated CT scans of the abdomen
      during treatment, and this diagnosis was verified histologically by liver biopsy.
      There was no relationship to cumulative IFN-alpha or 5-FU dose. Based on
      posttreatment CT scans, the liver parenchyma changes were reversible after
      therapy was stopped, and there were no significant clinical sequelae. No patients
      treated with 5-FU/leucovorin or 5-FU alone experienced a decreased CT value of
      the liver parenchyma. CONCLUSION: Hepatic steatosis was been observed in
      approximately 30% of patients treated with IFN-alpha and 5-FU. The hepatic
      changes were fully reversible after the treatment was stopped. Recognition of
      this condition is important to prevent a patient from being labeled as having
      progressive hepatic metastases.

PMID- 7736407
TI  - Modulation of P-glycoprotein activity by estramustine is limited by binding to
      plasma proteins.
AB  - BACKGROUND: Estramustine previously has been shown to interact with P
      glycoprotein and to restore intracellular accumulation of vinblastine and
      paclitaxel in cells overexpressing this drug transporter. However, the ability of
      estramustine to potentiate the cytotoxicities of several drugs was less than that
      expected. To resolve this apparent discordance, the authors examined the effects
      of serum on the actions of estramustine. METHODS: The cytotoxicities of
      anticancer drugs with or without estramustine or verapamil toward MCF-7 breast
      carcinoma cells and a P-glycoprotein-overexpressing subline MCF-7/ADR were
      determined using the sulforhodamine-binding assay. The extent of intracellular
      accumulation of [3H]vinblastine and [3H]paclitaxel was determined for each using
      standard methods, and the binding of radiolabeled drugs to plasma proteins was
      characterized by equilibrium dialysis. RESULTS: Without serum, the sensitivities
      of MCF-7/ADR cells to several P-glycoprotein-transported drugs were increased by
      estramustine and verapamil. Conversely, when the cells were treated with a 10%
      serum, the cytotoxicities of these drugs were increased by verapamil, but not by
      estramustine. Without serum, intracellular accumulation of [3H]vinblastine and
      [3H]paclitaxel by MCF-7/ADR cells was increased markedly by verapamil and
      estramustine; however, serum suppressed the effects of estramustine much more
      strongly than those of verapamil. Equilibrium dialysis experiments demonstrated
      that [3H]estramustine binds to plasma proteins, predominantly albumin, whereas
      [3H]paclitaxel binds to albumin and alpha 1-acid-glycoprotein, and
      [3H]vinblastine binds predominantly to alpha 1-acid-glycoprotein. CONCLUSION:
      Although estramustine can bind to P-glycoprotein, its effectiveness as a
      reversing agent in vivo likely is limited by binding to plasma proteins.

PMID- 7736408
TI  - Heterogeneity of cancer surveillance practices among medical oncologists in
      Washington and Oregon.
AB  - BACKGROUND: Medical oncologists provide long term care for patients who have been
      treated for cancer and are in remission. However, little is known about how
      physicians use routine laboratory and imaging tests for detecting cancer
      recurrence in their patients. METHODS: To assess type and level of their
      surveillance testing of patients with cancer who are in remission, a cross
      sectional survey of medical oncologists was performed. Seventy-three members of
      the American Society of Clinical Oncology residing in Washington and Oregon
      participated (70% response rate). Standardized questionnaires were mailed to
      medical oncologists using a multiple-mailing technique. Three scenarios, each
      describing a patient with cancer of the breast, colon, or prostate, were
      included. Participants were asked to indicate the frequency at which they would
      order seven different diagnostic tests in the routine follow-up of such patients.
      RESULTS: Virtually all respondents would practice some level of follow-up testing
      of their patients. Although testing practices did not vary significantly
      according to physician age, year of graduation, practice type, or state of
      residence, there was considerable variability from physician to physician.
      CONCLUSIONS: These results suggest that optimal cancer-surveillance testing
      programs for patients with cancer of the breast, colon, or prostate have not yet
      been satisfactorily defined.

PMID- 7736409
TI  - Repetitive low dose oral methotrexate and intravenous mercaptopurine treatment
      for patients with lower risk B-lineage acute lymphoblastic leukemia. A Pediatric
      Oncology Group pilot study.
AB  - BACKGROUND: This trial evaluated the toxicity and preliminary efficacy of a
      repeated oral low dose (LD) methotrexate schedule with intravenous mercaptopurine
      infusions as intensification therapy for children with lower risk B-lineage acute
      lymphoblastic leukemia (ALL). PATIENTS AND METHODS. From December 1986 to January
      1991, 96 children with newly diagnosed, lower risk ALL were enrolled.
      Vincristine, L-asparaginase, and prednisone were used for remission induction.
      Age-based methotrexate was administered intrathecally (IT) for central nervous
      system (CNS) prophylaxis. An outpatient-based intensification treatment included
      LD methotrexate 30 mg/M2 every 6 hours for 5 doses, followed by intravenous
      mercaptopurine 1000 mg/M2 for 6 hours every 2 weeks for 12 courses. Leucovorin
      rescue was administered 48 hours after methotrexate treatment was begun.
      Maintenance therapy included standard daily oral mercaptopurine, weekly
      intramuscular methotrexate, and IT methotrexate every 12 weeks, for 2 years.
      RESULTS: All patients had disease remission. Thirty-two patients relapsed; there
      were 17 isolated bone marrow relapses, 10 isolated CNS relapses, 2 isolated
      testicular relapses, 1 marrow plus CNS relapse, 1 marrow plus testicular relapse,
      and 1 CNS plus testicular relapse. Event free survival (EFS) at 4 years was 66%
      (standard error, 7%) by Kaplan-Meier analysis. Complications associated with LD
      methotrexate/mercaptopurine courses were few and resulted in hospital
      readmissions in 2.4% of courses. Two patients were unable to comply with the oral
      LD methotrexate schedule and received intravenous methotrexate. Three patients
      were unable to complete scheduled maintenance because of hepatic or hematopoietic
      dysfunction. CONCLUSIONS: Low dose methotrexate/mercaptopurine can be
      administered safely on an outpatient basis to children with lower risk B-lineage
      ALL. However, there was a higher than expected incidence of bone marrow and CNS
      relapse. The reasons for this outcome were not completely clear but raise the
      possibility that LD methotrexate therapy may be less effective in preventing
      relapse than are higher dose, parenteral methotrexate regimens.

PMID- 7736410
TI  - Matching pulmonary structure and perfusion via combined dynamic multislice CT and
      thin-slice high-resolution CT.
AB  - Taking advantage of two scan modes of an electron beam CT scanner (Imatron), we
      have developed a method utilizing x-ray CT for relating pulmonary perfusion to
      global and regional anatomy. A high temporal resolution mode, used to follow
      bolus contrast agent, is combined with a high spatial resolution mode to obtain
      the structure-function fusion. A software module has been developed for our image
      analysis package (VIDA) to automatically calculate physiologic parameters of flow
      and integrate these color coded functional measurements into a corresponding high
      spatial resolution data set. We present the scanning methodology details and give
      examples from our physiologic based research to demonstrate strengths of
      combining dynamic and high resolution CT to uniquely characterize pulmonary
      normal and pathophysiology.

PMID- 7736411
TI  - 3D functional mapping of left ventricular dynamics.
AB  - The heart is an organ which functions by a periodic change of the three
      dimensional (3D) spatially distributed parameters; malfunctions of the heart's
      operating systems are manifested by changes of the spatio-temporal heart shape
      dynamics. A comprehensive quantitative study of this dynamic shape-function
      relationship is restricted by the partial character of the available data sets
      obtained by conventional imaging technologies and by limitations of the image
      analysis tools. This paper attempts to present a set of image analysis tools
      aimed at a thorough study of the left ventricular (LV) shape-function
      relationship based on Cine CT data. Data processing methodologies aimed at
      analysis and interpretation of the dynamic 3D LV shape, thickening and motion are
      described. These include the computerized detection of the LV boundaries, dynamic
      reconstruction of 3D LV shape, the LV shape parameters and their spatio-temporal
      evolution. The procedures are demonstrated using Cine CT images of the human LV
      in normal and pathological cases.

PMID- 7736412
TI  - IMPROMPTU: a system for automatic 3D medical image-analysis.
AB  - The utility of three-dimensional (3D) medical imaging is hampered by difficulties
      in extracting anatomical regions and making measurements in 3D images. Presently,
      a user is generally forced to use time-consuming, subjective, manual methods,
      such as slice tracing and region painting, to define regions of interest.
      Automatic image-analysis methods can ameliorate the difficulties of manual
      methods. This paper describes a graphical user interface (GUI) system for
      constructing automatic image-analysis processes for 3D medical-imaging
      applications. The system, referred to as IMPROMPTU, provides a user-friendly
      environment for prototyping, testing and executing complex image-analysis
      processes. IMPROMPTU can stand alone or it can interact with an existing graphics
      based 3D medical image-analysis package (VIDA), giving a strong environment for
      3D image-analysis, consisting of tools for visualization, manual interaction, and
      automatic processing. IMPROMPTU links to a large library of 1D, 2D, and 3D image
      processing functions, referred to as VIPLIB, but a user can easily link in custom
      made functions. 3D applications of the system are given for left-ventricular
      chamber, myocardial, and upper-airway extractions.

PMID- 7736413
TI  - A method for measurement of cross sectional area, segment length, and branching
      angle of airway tree structures in situ.
AB  - Accurate quantitative measurements of airway and vascular dimensions are
      essential for evaluating function in both the normal and in the diseased lung.
      This report describes a new integrated method for three-dimensional (3D)
      extraction and analysis of pulmonary tree structures using data from High
      Resolution Computed Tomography (HRCT). Serially scanned two-dimensional (2D)
      slices of the lower left lobe of isolated dog lungs were stacked to create a
      volume of data. Airway and vascular trees were extracted using a 3D seeded region
      growing algorithm based on differences in CT number between wall and lumen. In
      the region-growing step, voxels in the lumen are tagged with a distance
      descriptor to identify points along the tree structure equidistant from the seed
      point. To obtain quantitative data, we reduced each tree to its central axis.
      From the central axis, branch length was measured as the distance between two
      successive branch points, branch angle was measured as the angle produced by two
      daughter branches, and cross-sectional area was measured from a plane
      perpendicular to the central axis point. Data derived from these methods can be
      used to localize and quantify structural differences both during different
      physiologic conditions and in pathologic lungs.

PMID- 7736414
TI  - Representation and display of three-dimensional medical images using a linear
      octree.
AB  - A data structure called a linear octree which represents volumetric information
      by an eight-way branching tree is reviewed along with the procedure for
      converting the rectangular coordinates of a given octree node to an equivalent
      locational code, and vice versa. A brief description of a display algorithm of
      linear octree encoded objects is outlined. This display algorithm is based on an
      explicit formula which computes the coordinates of any vertex of any linear
      octree node in terms of the coordinates of the corners of the universe using only
      additions and multiplications of powers of 2. When performing display operations,
      the standard matrix transformations need only be applied once to the main
      vertices of the universe cube. The projections of all the other nodes of a linear
      octree are computed using this simple formula.

PMID- 7736415
TI  - VLSI in biomedical imaging systems.
AB  - This paper explores the nature of Very Large Scale Integration (VLSI) systems as
      applied to the area of medical imaging systems. A general discussion of imaging
      systems and the techniques employed therein will be presented. With this, the
      merits of VLSI solutions to the medical imaging problem are presented.
      Consideration is also given to programmable processors, such as off the shelf DSP
      processors, semi-custom, and full custom VLSI devices. Through the use of VLSI
      devices, many image processing algorithms can be integrated into a hardware
      solution. This has the advantage of increased computational capacity over
      solutions that would normally employ software techniques.

PMID- 7736416
TI  - Left ventricular boundary detection from spatio-temporal volumetric computed
      tomography images.
AB  - This paper presents a new automatic technique for left ventricle boundary
      detection from a set of three-dimensional (3D) computed tomography (CT)
      volumetric cardiac images. The goals of this paper are to incorporate the
      temporal information into LV boundary detection, to link the shape modeling and
      LV boundary detection together, and to provide a compact representation of
      recovered LV boundaries to cardiac imaging. The proposed technique introduces
      spatio-temporal boundary detection and iterative model-based boundary refinement
      to left ventricular boundary extraction. The proposed technique has been applied
      to two sets of four-dimensional (4D) computed tomography images. Experimental
      results are compared with the manually edited images.

PMID- 7736417
TI  - Biomedical imaging modalities: a tutorial.
AB  - The introduction of advanced imaging technologies has improved significantly the
      quality of medical care available to patients. Non-invasive imaging modalities
      allow a physician to make increasingly accurate diagnoses and render precise and
      measured modes of treatment. Current uses of imaging technologies include
      laboratory medicine, surgery, radiation therapy, nuclear medicine, and diagnostic
      radiology. This paper provides an overview of most of the popular imaging
      modalities currently in clinical use. It is hoped that a general understanding of
      the modality from which an image is derived will help researchers in the
      subsequent analysis of the image data.

PMID- 7736418
TI  - Supervised interpretation of echocardiograms with a psychological model of expert
      supervision.
AB  - We have developed a collaborative scheme that facilitates active human
      supervision of the binary segmentation of an echocardiogram. The scheme
      complements the reliability of a human expert with the precision of segmentation
      algorithms. In the developed system, an expert user compares the computer
      generated segmentation with the original image in a user friendly graphics
      environment, and interactively indicates the incorrectly classified regions
      either by pointing or by circling. The precise boundaries of the indicated
      regions are computed by studying original image properties at that region, and a
      human visual attention distribution map obtained from the published psychological
      and psychophysical research. We use the developed system to extract contours of
      heart chambers from a sequence of two dimensional echocardiograms. We are
      currently extending this method to incorporate a richer set of inputs from the
      human supervisor, to facilitate multi-classification of image regions depending
      on their functionality. We are integrating into our system the knowledge related
      constraints that cardiologists use, to improve the capabilities of our existing
      system. This extension involves developing a psychological model of expert
      reasoning, functional and relational models of typical views in echocardiograms,
      and corresponding interface modifications to map the suggested actions to image
      processing algorithms.

PMID- 7736419
TI  - Segmentation of multidimensional cardiac images.
AB  - One of the initial steps in the analysis of three-dimensional (3D)/four
      dimensional (4D) images is Segmentation, which entails partitioning the images
      into relevant subsets such as object and background. In this paper, we present a
      multidimensional segmentation algorithm to extract object surfaces from
      Multidimensional Cardiac Computed Tomography (CT) scans. We propose the
      Generalized Morphological operators for segmentation in multidimensions. A priori
      knowledge of the approximate location of the object surface is communicated to
      the algorithm via the definition of the Search Space. The algorithm uses this
      definition of the Search Space to obtain the Surface Candidate elements. The
      search space specification reduces the computational cost and increases the
      reliability of the detected features.

PMID- 7736420
TI  - A dynamic finite element surface model for segmentation and tracking in
      multidimensional medical images with application to cardiac 4D image analysis.
AB  - This paper presents a physics-based approach to anatomical surface segmentation,
      reconstruction, and tracking in multidimensional medical images. The approach
      makes use of a dynamic "balloon" model--a spherical thin-plate under tension
      surface spline which deforms elastically to fit the image data. The fitting
      process is mediated by internal forces stemming from the elastic properties of
      the spline and external forces which are produced form the data. The forces
      interact in accordance with Lagrangian equations of motion that adjust the
      model's deformational degrees of freedom to fit the data. We employ the finite
      element method to represent the continuous surface in the form of weighted sums
      of local polynomial basis functions. We use a quintic triangular finite element
      whose nodal variables include positions as well as the first and second partial
      derivatives of the surface. We describe a system, implemented on a high
      performance graphics workstation, which applies the model fitting technique to
      the segmentation of the cardiac LV surface in volume (3D) CT images and LV
      tracking in dynamic volume (4D) CT images to estimate its nonrigid motion over
      the cardiac cycle. The system features a graphical user interface which minimizes
      error by affording specialist users interactive control over the dynamic model
      fitting process.

PMID- 7736421
TI  - CT volumetric data-based left ventricle motion estimation: an integrated
      approach.
AB  - This paper describes a novel approach to left ventricle motion analysis via the
      integration of image segmentation with shape deformation analysis using
      computerized tomography (CT) volumetric image data. This approach is different
      from traditional image analysis scenario in which the image segmentation and
      shape analysis were considered separately. The advantage of integrating the image
      segmentation with the shape analysis lies in the fact that the shape
      characteristics of the object can be used as effective constraints in the process
      of segmentation while original image data can be made useful along with the
      segmentation results in the process of shape analysis. In the case of left
      ventricle motion estimation, such an integration can be applied to obtain the
      estimation results that are consistent with both given image data and a priori
      shape knowledge. The initial segmentation of the images is obtained through
      adaptive K-mean classification and the region-of-interest is then identified
      based on the initial segmentation. The shape analysis is accomplished through
      fitting the boundary points of the region-of-interest to the surface modeling
      primitives. These two processes are integrated through the feedforward and
      feedback channels so that the surface fitting is constrained by the confidence
      measures of the boundary points and segmentation refinement is guided by the
      result of surface modeling. Global motion parameters are obtained by comparing
      the parameters of the fitted surface model at consecutive time instances. The
      segmentation and shape analysis results obtained show that the integrated
      approach is capable of providing promising improvement over traditional
      approaches.

PMID- 7736422
TI  - Refined localization of the erbB-3 proto-oncogene by direct visualization of FISH
      signals on LUT-inverted and contrast-enhanced digital images of DAPI-banded
      chromosomes.
AB  - Contrast-enhanced, look-up-table (LUT)-inverted digital images of DAPI-banded
      chromosomes after fluorescence in situ hybridization (FISH) permit direct
      regional chromosomal localization of the fluorescent signals of single-copy gene
      probes. Improved quality and resolution of chromosome banding allowed a refined
      localization of the erbB-3 protooncogene from chromosome band 12q13 to sub-bands
      12q13.2-13.3. This procedure can be used for direct and precise mapping of single
      copy genes on both normal and cancer-cell-rearranged chromosomes.

PMID- 7736423
TI  - Cytogenetic findings in uterine epithelioid leiomyomas.
AB  - Epithelioid leiomyomas of the uterus, unlike ordinary leiomyomas, show
      substantial epithelial differentiation. No chromosome abnormalities have been
      reported in uterine epithelioid leiomyomas before. We analyzed short-term
      cultures from five such tumors and detected abnormal karyotypes in four. A del(7)
      (q21.2q31.2) was found in two tumors, in one as the only change and in the other
      as a secondary aberration acquired during clonal evolution. Rearrangement of
      chromosomal band 12q15, another of the cytogenetic hallmarks of ordinary uterine
      leiomyomas, was seen in the form of a t(10;12) in one tumor. Band 17q21 was
      involved in structural aberrations in two cases. The data we present indicate
      that epithelioid leiomyomas are fundamentally similar cytogenetically, and hence
      presumably also pathogenetically, to the much more common smooth muscle
      differentiated uterine myomas. The only differences hinted at are that
      epithelioid tumors may be karyotypically more complex and more often have
      rearrangements of 17q21.

PMID- 7736424
TI  - Solid alveolar rhabdomyosarcoma with a t(2;13).
AB  - We report a child with a progressive "solid alveolar rhabdomyosarcoma" in whom
      analysis of tumor cells revealed a t(2;13) translocation characteristic of the
      classical alveolar subtype. Both subtypes of alveolar rhabdomyosarcoma are
      associated with a poor response to treatment and the occurrence of this
      translocation in both is suggestive of a common biologic origin.

PMID- 7736425
TI  - Near-diploid karyotypes with recurrent chromosome abnormalities characterize
      early-stage endometrial cancer.
AB  - Cytogenetic investigation was attempted on 15 endometrial tumors. Whenever
      possible, a combination of direct harvesting and short-term culture (with or
      without prior methotrexate synchronization) was used. The analysis was successful
      in 13 cases: 12 carcinomas of stage I and one atypical hyperplasia. Clonal
      abnormalities were found in 10 tumors, whereas the remaining three showed a
      normal karyotype. The modal chromosome number was near-diploid. The abnormal
      karyotypes contained relatively simple numerical or structural aberrations in all
      but one tumor, a serous papillary carcinoma with multiple complex changes as well
      as cytogenetic evidence of intratumor heterogeneity. Gain of 1q, trisomy for
      chromosomes 2, 7, 10 (this trisomy was shown by in situ hybridization to be
      present also in a large number of interphase cells), and 12, and loss of
      chromosome 22 were recurrent aberrations; these are also the cytogenetic
      anomalies that have been consistently associated with endometrial carcinomas in
      previous studies. The utilization of both direct harvesting and short-term
      culture in several cases increased the frequency with which abnormal karyotypes
      were found; sometimes aberrations were found by the first method but not by the
      other, and vice versa. Never were different clonal anomalies found by the two
      approaches in the same case. Synchronization of the cultures generally led to
      chromosome preparations with more mitoses and of better quality. Again, no
      different anomalies were found in synchronized and standard cultures from the
      same tumor.

PMID- 7736426
TI  - Sister chromatid exchange (SCE) studies in breast cancer patients: a follow-up
      study.
AB  - Sister chromatid exchanges (SCEs) were studied in 20 patients with breast cancer
      (stage II) before surgery, one month after surgery, and after three years as a
      follow-up study. Data from 50 age-matched, normal healthy females, preferably
      from the affected families, served as controls. In each patient, 50 well-spread
      metaphases were scored for SCEs. The mean values of SCEs per metaphase were 5.80,
      4.69, and 5.98 in breast cancer patients before surgery, one month after surgery,
      and after a gap of three years as a follow-up, respectively. The one-way analysis
      of variance was applied and it was found that there was a highly significant
      difference in the frequency of sister chromatid exchanges in these patients
      before surgery, one month after surgical removal of cancerous tissue, and after
      three years as a follow-up study. The elevated level of SCEs three years after
      surgical removal of cancerous tissue predict the chances of development of
      another type of cancer.

PMID- 7736427
TI  - Chromosome analysis of uterine adenomyosis. Detection of the leiomyoma-associated
      del(7q) in three cases.
AB  - Adenomyosis is a uterine disease whose defining characteristic is the presence
      deep in the myometrium of endometrial glands and stroma. The condition is
      believed to arise from inordinate downward growth by contiguity from the
      endometrium rather than from in situ metaplasia or neoplasia. No acquired
      chromosome abnormalities have been associated with adenomyosis before. We
      analyzed short-term cultures from three cases and detected in all of them a
      del(7) (q21.2q31.2), a karyotypic anomaly that has hitherto been found repeatedly
      only in uterine leiomyomas. The cytogenetic similarity to leiomyoma suggests that
      the del(7q) was present in the mesenchymal or, more precisely, smooth muscle
      cells of the adenomyosis lesions. The very fact that clonal chromosome
      abnormalities were present questions whether the prevailing understanding of
      adenomyosis pathogenesis is adequate; the cytogenetic data would better fit a
      model of the disease envisioning the intramyometrial endometrial foci as having
      arisen through a neoplastic process.

PMID- 7736428
TI  - 5q- syndrome in a child.
AB  - A boy aged 8 years, 10 months presented with refractory anemia. Bone marrow
      investigation revealed monolobular megakaryocytes. Cytogenetic analysis showed a
      clonal abnormality: 46, XY, del(5)(q14q32). This is the youngest individual ever
      reported with this disorder. A year after diagnosis, while on treatment with
      human recombinant erythropoietin, the bone marrow showed an excess of blasts. No
      bone marrow donor could be found. Transformation to acute myelomonocytic leukemia
      occurred 3 months later. In spite of intensive chemotherapy, the child died of
      progressive disease with massive splenomegaly and jaundice. The case illustrates
      that the 5q- syndrome can occur de novo in children. The outcome in this child
      was poor, which may reflect a difference from the adult 5q- syndrome or may
      possibly be related to the erythropoietin the child received.

PMID- 7736429
TI  - Comparison of DNA content in non-Hodgkin's lymphoma as measured by flow cytometry
      and cytogenetics.
AB  - Specific cytogenetic changes such as t(14;18) and t(8;14) are associated with
      specific histologic subtypes of non-Hodgkin's lymphoma (NHL) and may predict
      disease outcome. Nonspecific cytogenetic changes include other structural
      rearrangements or numerical changes such as monosomies and trisomies, which may
      cause changes in total cellular DNA content. In many solid tumors, the presence
      of abnormal DNA content may be predictive of clinical behavior. NHL biopsies,
      however, contain normal (diploid) as well as abnormal cells, and DNA changes in
      the peridiploid range are detectable by cytogenetic analysis, but not
      consistently by flow cytometry. In the present study, we performed flow
      cytometric and cytogenetic analysis of DNA on biopsies from 129 patients with non
      Hodgkin's lymphoma (NHL). Cytogenetic studies were successful on 88 (68%) of the
      samples. There was 55% concordance between flow cytometric and cytogenetic
      techniques in detecting aneuploid DNA content, with the majority of discrepancies
      occurring in the peridiploid range. We also detected six samples which were
      aneuploid by flow cytometry, but diploid by cytogenetics. We suggest that a
      reasonable approach to determine DNA content, as it relates to prediction of
      outcome in NHL, would be to combine data from both of these techniques and
      analyze the results in terms of ranges of DNA rather than by categorizing as
      diploid versus aneuploid.

PMID- 7736430
TI  - Phorbol-12,13-dibutyrate improves the quality of cytogenetic preparation in
      lymphoid malignancies.
AB  - In cytogenetic preparation of lymphoid malignancies we investigated the
      quantitative and qualitative impact of phorbol-12,-13-dibutyrate (P) and of this
      tumor promoter in combination with the calcium ionophore A23187 (PA). Using
      parallel cultures of unstimulated and stimulated preparations, the effect was
      examined in 13 patients with malignant lymphomas and six patients with acute
      lymphoblastic leukemias (ALL). Focusing on high-quality analyzable metaphases,
      the best results were found in seven of 13 cases with lymphomas and five of six
      patients with ALL in the cultures supplemented with phorbol-12,13-dibutyrate. The
      yield of metaphases of good quality regarding length, spreading, and banding of
      chromosomes was regularly better in P-stimulated 24-hour culture (p < 0.05),
      followed by 48-hour cultures stimulated with P alone. Addition of the calcium
      ionophore was of no further benefit. The yield of the unstimulated direct harvest
      was rather poor in nearly all patients investigated. Because no mutagenic effect
      of P was observed, the use of this mitogen may offer interesting perspectives in
      cytogenetic analysis of lymphoid malignancies and perhaps also in other tumors
      with low mitotic indexes.

PMID- 7736431
TI  - Translocation (X;14)(p11;q32) in a patient with refractory anemia.

PMID- 7736432
TI  - Cytogenetic characterization of three human and three rat medullary thyroid
      carcinoma cell lines.
AB  - Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor of the thyroid C
      cells. MTC may arise as a sporadic tumor or as a component of one of three
      autosomal dominant familial cancer syndromes, MEN 2A, MEN 2B, or familial MTC.
      Recent studies have identified mutations of the RET proto-oncogene in the
      proximal long arm of chromosome 10, which are thought to be causative for these
      syndromes. To facilitate the search for other genes involved in the development
      of MTC, we characterized cytogenetically three human MTC cell lines and three rat
      MTC cell lines. The human cell lines studied were TT and RO-H85-1, previously
      reported, and an uncharacterized cell line, MZ-CRC-1, derived from a malignant
      pleural effusion from a patient with metastatic MTC. The rat MTC cell lines
      characterized were CA-77, 6-23C6, and 44-2. Cytogenetic abnormalities present in
      the human and rat cell lines were compared with 13 reported cytogenetic studies
      of human MTC tumors and three other cytogenetically analyzed MTC cell lines. The
      human 9q/rat 3 and human 3p/rat 15 chromosomes were affected in six of the
      comparable cell lines and tumors. These findings suggest human chromosome regions
      9q and 3p may contain genes involved in the pathogenesis of MTC.

PMID- 7736433
TI  - Constitutional trisomy 8 mosaicism and gestational trophoblastic disease.
AB  - Concurrence of congenital trisomy 8 mosaicism and gestational trophoblastic
      disease in a 42-year-old gravida IV, para IV female is described in the present
      report. In contrast to other cases described in the literature, our patient had
      no known additional confounding chromosomal abnormalities other than trisomy 8.
      The finding of trisomy 8 mosaicism in yet another type of cancer provides further
      support for the hypothesis of an increased predisposition to cancer in tissues
      with constitutional genomic imbalance, which can manifest itself as numerical
      chromosomal abnormalities (e.g., trisomies) or structural chromosomal
      abnormalities (e.g., translocations). To the best of our knowledge, this is the
      only report in the English literature of constitutional trisomy 8 mosaicism
      associated with gestational trophoblastic disease, a rare gynecologic disease
      entity in itself.

PMID- 7736434
TI  - A novel translocation involving chromosomes 2, 9, 14, and 22 in chronic myeloid
      leukemia.
AB  - A 46-year-old man with chronic myelogenous leukemia was found to have a new
      complex translocation. In chronic phase, all of the bone marrow cells had a
      rearrangement of a t(2;9;14;22) (p21;q34;q32;q11). Southern blot analysis of
      leukocyte DNA revealed rearrangement of the breakpoint cluster region (bcr)
      within the 5.8-Kb bcr. The patient eventually died in blast crisis 28 months
      later. The cytogenetic findings of bone marrow cells showed a
      46,XY,t(2;9;14;22)(p21;q34;q32;q11),add(1p),del(3q) karyotype in blast crisis.

PMID- 7736435
TI  - Interstitial del(12)(q15q22) in myelodysplastic syndromes.
AB  - A patient with a myelodysplastic syndrome and a 12q deletion was studied and
      followed-up. After 10 years and several cytogenetic studies, it is suggested that
      this abnormality can be the sole chromosomal change in myelodysplastic syndromes.

PMID- 7736436
TI  - A variant t(14;17) in acute promyelocytic leukemia. Positive response to retinoic
      acid treatment.
AB  - We present a case of acute promyelocytic leukemia (APL) carrying an atypical
      translocation involving chromosomes 14 and 17. This translocation could be
      considered a variant of the APL-specific t(15;17). Positive response to retinoic
      acid treatment suggests molecular rearrangement of retinoic acid receptor alpha.

PMID- 7736437
TI  - Acute lymphoblastic leukemia with a variant Philadelphia translocation, der(9),
      and der(19) chromosomes.
AB  - We report here one of 15 cases of acute lymphoblastic leukemia (ALL)
      cytogenetically studied, with hypodiploidy, a variant Ph translocation, and
      der(9) and der(19) chromosomes. The patient, a 14-year-old girl, underwent
      combination chemotherapy and bone marrow transplantation and is still in
      remission 22 months after transplantation.

PMID- 7736438
TI  - Translocation (11;19)(q21;p13.1) in mucoepidermoid carcinoma of salivary gland.

PMID- 7736439
TI  - Complementation of bloom cellular phenotype by human chromosome 15.

PMID- 7736440
TI  - Cytogenetic findings in a metastatic renal cell carcinoma.

PMID- 7736441
TI  - Mechanism of origin of the isochromosome i(17q)

PMID- 7736442
TI  - Trisomy and disomy in tumors.

PMID- 7736443
TI  - Characterization of 20q deletions in patients with myeloproliferative disorders
      or myelodysplastic syndromes.
AB  - Deletions of the long arm of chromosome 20 are associated with several myeloid
      malignancies. We have analyzed the structure of the del(20q) in 30 patients and
      two cell lines. Twenty-one of the patients presented with a myeloproliferative
      disorder and nine with a myelodysplastic syndrome. Two categories of deletions
      were identified. Eighteen patients had a large deletion with loss of both G(+)
      bands from the long arm of chromosome 20. Twelve patients had small deletions
      with loss of one G(+) band from the long arm of chromosome 20. A chromosome paint
      was generated from a del 20q marker carrying a small deletion. This probe was
      hybridized to normal metaphases (reverse chromosome painting) and also to
      metaphases from patients with a del 20q (comparative reverse chromosome
      painting). All six small deletions analyzed were characterized by loss of the
      proximal G(+) band (q12) and retention of the distal G(+) band (q13.2). These
      data define a minimal deleted region extending from 20q11.2-20q13.1.

PMID- 7736444
TI  - Detection of PML-RAR alpha fusion transcript in Ph positive leukemia with acute
      promyelocytic phenotype lacking the t(15;17) cytogenetic abnormality.
AB  - A 39-year-old woman was diagnosed with acute promyelocytic leukemia (APL) with
      disseminated intravascular coagulation syndrome. The hematologic examination
      showed a morphologic, cytochemical, and immunophenotypic picture typical of an
      APL, with a marked leukocytosis and a mixed population of hypergranular and
      microgranular promyelocytes. The cytogenetic analysis showed a 46,XX,t(9;22)
      karyotype, without any alterations of chromosomes 15 and 17. The t(15;17)
      translocation was not evident in FISH experiments, while a molecular analysis
      revealed the presence of a PML-RAR alpha chimera.

PMID- 7736445
TI  - Clinical significance of quantitative analysis of carcinoembryonic antigen
      assessed by flow cytometry in fresh human gastric cancer cells.
AB  - The expression of carcinoembryonic antigen(CEA) on tumor cells freshly excised
      from 51 patients with gastric cancer was studied using flow cytometry. The
      expression of CEA by flow cytometry was more quantitative than that by
      immunohistochemical staining. There was no relationship between the fluorescence
      intensity assessed by flow cytometry and serum CEA levels, except for patients
      with a high titer of serum CEA. The patients with high grade CEA expression on
      tumor cells by flow cytometry had poor prognoses, compared to patients with low
      CEA expression in undifferentiated gastric cancer. Thus, it is suggested that the
      quantitative CEA expression on tumor cells by flow cytometry could be a useful
      prognostic marker in postoperative gastric cancer patients.

PMID- 7736446
TI  - Fibronectin and sialic acid levels in human meningiomas and gliomas.
AB  - In this study, fibronectin and sialic acid levels have been assayed in human
      meningiomas and gliomas. The mean fibronectin and sialic acid levels for human
      meningiomas were 22.01 +/- 9.70 micrograms/mg protein and 19.58 +/- 4.89
      micrograms/mg protein, respectively, and for human gliomas were 27.30 +/- 13.70
      micrograms/mg protein and 25.67 +/- 11.60 micrograms/mg protein, respectively,
      versus 9.23 +/- 5.40 micrograms/mg protein and 13.50 +/- 4.30 micrograms/mg
      protein for normal brain tissues. Fibronectin and sialic acid levels were
      significantly higher in human meningiomas (P < 0.01 and P < 0.05) and gliomas (P
      < 0.001 and P < 0.01) than control group. Also the mean fibronectin and sialic
      acid levels were found to be 18.27 +/- 7.08 micrograms/mg protein and 17.04 +/-
      6.25 micrograms/mg protein in Grade I-II and 32.60 +/- 15.00 micrograms/mg
      protein and 29.50 +/- 11.60 micrograms/mg protein in Grade III-IV gliomas,
      respectively. Fibronectin and sialic acid levels were significantly higher in
      Grade III-IV gliomas than Grade I-II gliomas (P < 0.05).

PMID- 7736447
TI  - Heparin receptors in two murine mammary adenocarcinomas with different metastatic
      ability: relationship with growth inhibition.
AB  - Binding of heparin to primary cultured cells of two murine mammary
      adenocarcinomas with low (M3) and high (MM3) lung, metastatic capacity was
      determined. Heparin binding was rapid, specific and saturable. MM3 cells grown
      for 24 h in fetal calf serum (FCS)-free medium exhibited a higher number of
      binding sites for 3H-heparin [(11 +/- 1) x 10(5) sites per cell than M3 cells
      [(6.9 +/- 0.6) x 10(5) sites per cell]. However, when M3 cells were grown in the
      presence of 2% FCS, they showed less heparin binding sites [(3.5 +/- 0.4) x 10(5)
      sites per cell]. In contrast, dissociation constants were very similar for MM3
      and M3 cells grown with or without FCS (Kd = 2-4 x 10(-9) M). Furthermore,
      heparin inhibited MM3 and M3 cell growth both in the absence or presence of FCS.
      Competition studies showed that chemically modified heparins lacking
      antiproliferative effect (O-desulfated; O/N-desulfated N-acetylated and N
      desulfated heparins) were not able to inhibit 3H-heparin binding. N-desulfated N
      acetylated heparin, which had partial antiproliferative effect, partially
      inhibited 3H-heparin binding, while heparin with a high antiproliferative
      activity inhibited more than 90% 3H-heparin binding. The antiproliferative effect
      of heparin and chemically modified heparins seems to be related to their binding
      ability to the cell membrane.

PMID- 7736448
TI  - Noncovalent binding of a mitomycin C metabolite, 2,7-diaminomitosene, to duplex
      DNA.
AB  - The major metabolite of mitomycin C, 2,7-diaminomitosene (DAM), interacts
      noncovalently with DNA. This was supported by ultraviolet-visible spectrum
      changes upon mixing with DNA and ethidium bromide displacement from DNA, measured
      as fluorescence changes. Moreover, DAM bound to DNA sufficiently strongly to hold
      DNA in a double stranded conformation under denaturing gel electrophoresis
      conditions commonly used to measure mitomycin C cross-links. These data show that
      generation of DAM and interaction with DNA represent a potential additional
      mechanism of DNA damage induced by mitomycin C.

PMID- 7736449
TI  - DNA repair enzyme expression in chronic lymphocytic leukemia vis-a-vis nitrogen
      mustard drug resistance.
AB  - Nitrogen mustard resistance in B-cell chronic lymphocytic leukemia (B-CLL) has
      been associated with enhanced DNA repair and increased expression of DNA repair
      enzymes. Lymphocytes from patients with nitrogen mustard resistant B-CLL
      displayed a fivefold increase in resistance to melphalan in vitro as compared to
      those from untreated patients concordant with our definition of clinical
      resistance. We have performed Northern analysis using a cohort consisting of 11
      untreated and 12 treated-resistant patients. Increased expression of ERCC-1 was
      not found to be associated with nitrogen mustard resistance, nor did we find
      altered expression of the DNA repair enzymes: ERCC-2, DNA polymerase beta, or
      topoisomerase I. There was also no difference in the levels of ERCC-1 protein
      between melphalan sensitive and resistant B-CLL lymphocytes. Analysis of genes
      involved in nitrogen mustard detoxification revealed that metallothionein was
      weakly expressed, while transcripts encoding glutathione-S-transferase alpha were
      undetectable. Thus, it is unlikely either of these proteins plays a role in the
      resistance. The results of the cytotoxicity assay validate the use of B-CLL as a
      model to study nitrogen mustard resistance. This model allows us to perform in
      vitro studies using a tumor which develops resistance in vivo. The results of
      this study suggest that nucleotide excision repair, as represented by ERCC-1 and
      ERCC-2, is not the limiting step in B-CLL nitrogen mustard resistance.

PMID- 7736450
TI  - Decreased plasma levels of cholecystokinin in healthy males after chronic
      ingestion of a heat-treated soya product.
AB  - Administration of raw soya containing a trypsin inhibitor stimulated excessive
      release of cholecystokinin (CCK) which led to pancreatic hypertrophy, hyperplasia
      and cancer in the rats (Booth et al. (1964) Proc. Soc. Exp. Biol. Med., 116,
      1067). More postprandial CCK release in healthy humans was observed after
      ingestion of a single dose of raw soya than heat-treated soya (Calam et al.
      (1989) Br. J. Nutr., 58, 175). The effect of chronic ingestion of a heat-treated
      soya product on postprandial CCK release was investigated in six healthy adult
      males after ingestion of a 36-oz. portion of soymilk daily for 1 month and at 2-3
      months after termination of soymilk ingestion. Subjects fasted for 15 h, ingested
      Lipomul (1.5 g/kg) and provided blood at timed intervals for CCK analysis. The
      results show that 1-month ingestion of soymilk decreased the magnitude of Lipomul
      induced postprandial CCK release in plasma of all six subjects by 5-60% (P <
      0.05) compared to those obtained at 2-3 months after the withdrawal from soymilk
      ingestion. Plasma pancreatic polypeptide (PP) levels were similarly decreased in
      five of the six subjects by 19-67% (P = 0.03) in line with the regulation of PP
      by CCK. Thus, prolonged exposure of humans to a heat-treated soya inhibited
      slightly meal-induced CCK release in contrast to that found in rats after raw
      soya diets.

PMID- 7736451
TI  - 8-hydroxydeoxyguanosine levels in DNA of human breast cancer are not
      significantly different from those of non-cancerous breast tissues by the HPLC
      ECD method.
AB  - 8-Hydroxydeoxyguanosine (oh8dG) is a promutagenic DNA lesion produced by oxygen
      radicals, and a high level of 8-hydroxyguanine in breast cancers was previously
      demonstrated by the gas chromatography-mass-spectrometry method. To confirm the
      previous observation, the oh8dG levels of DNA of 22 breast cancers and
      corresponding adjacent non-cancerous breast tissues were analyzed by high
      performance liquid chromatography-electrochemical detector (HPLC-ECD) system, and
      the correlation of the oh8dG levels in breast cancer DNAs with clinical and
      immunohistochemical parameters was examined. However, the levels of oh8dG in DNA
      of breast cancers are not significantly different from those of corresponding non
      cancerous breast tissues (P = 0.084) by the HPLC-ECD method. Furthermore, the
      oh8dG levels in breast cancers were not associated with p53 and erbB-2
      immunoreactions, with expression of estrogen and progesterone receptors, and with
      clinical stage and histological grade. Thus, in contrast to the previous data,
      the present study using the HPLC-ECD method does not indicate an increase of
      oh8dG levels in breast cancers.

PMID- 7736452
TI  - Photodynamic therapy of photofrin II and excimer dye laser on experimental
      tumors.
AB  - Photodynamic therapy (PDT) by combination of photofrin II and excimer dye laser
      was evaluated for its usefulness in experimental tumors. High antitumor effects
      of PDT on sarcoma 180 solid type were obtained when PDT was performed with laser
      irradiation at an energy of 50 or 100 J/cm2 (40 or 80 Hz, 4 mJ/pulse) 48 h after
      i.v. administration of photofrin II at a dose of 25 mg/kg. Under the same
      conditions, the antitumor effects of PDT on murine Lewis lung carcinoma, human
      fibrosarcoma HT-1080 and human bladder transitional cell carcinoma KK-47 were
      also observed. These results suggest that clinical application of PDT with
      photofrin II and excimer dye laser might be useful.

PMID- 7736453
TI  - Refractoriness to mammary carcinogenesis in the parous mouse is reversible by
      hormonal stimulation induced by pituitary isografts.
AB  - We have previously reported that mouse mammary epithelial cells transformed in
      vitro yield tumors which vary qualitatively and quantitatively as a function of
      the mitogenic environment in which the cells are propagated at the time of
      carcinogen treatment. One milieu supportive of transformation in vitro was medium
      supplemented with progesterone and prolactin as the mitogens. We have performed
      parallel studies in which virgin mice were isografted with pituitaries resulting
      in elevated serum titers of progesterone and prolactin. After carcinogen
      treatment, these mice developed mammary tumors which included those identical
      genotypically and phenotypically to tumors induced in vitro in cells grown in
      progesterone and prolactin during carcinogen exposure. Our current working
      hypothesis is that the mitogenic environment around the time of carcinogen
      administration can modulate the incidence and phenotype of the resultant tumors.
      To further test this hypothesis, we have evaluated the susceptibility of
      hormonally-stimulated parous mice to chemically induced mammary carcinogenesis
      since parity is known to significantly reduce the susceptibility of the mouse
      mammary gland to carcinogenesis. Virgin or multiparous BALB/c mice were
      isografted with two pituitaries. Five weeks after surgery, the mice were injected
      with N-methyl-N-nitrosourea (MNU; 50 micrograms/g i.v.). Mammary carcinomas arose
      in 85% (11/13) with a median latency of 22.8 weeks and 1.9 tumors per virgin
      mouse and 80% (24/30) with a median latency of 22.1 weeks at a frequency of 1.9
      tumors per parous mouse. Only 14% (2/14) of the non-isografted, age-matched
      parous controls developed tumors when injected with MNU. Fourteen parous mice
      receiving only pituitary isografts (no MNU), did not develop mammary carcinomas
      within the 7-month period of the study. These results demonstrate that parous
      BALB/c mice are refractory to MNU-induced mammary carcinogenesis and that this
      refractoriness is not permanent, but can be overcome by hormonal stimulation
      mediated by pituitary isografts.

PMID- 7736454
TI  - Immunohistochemical characterization of 'small, lymphoid-like cell populations'
      within germinomas: immunologic and molecular approaches to diagnosis.
AB  - Little is known to date about the biological and molecular characteristics of
      'small lymphoid cells' within intracranial germinomas. Frozen sections from three
      germinoma specimens were evaluated immunohistochemically in order to identify
      phenotypic markers expressed on human lymphoid cells as well as intercellular
      adhesion molecules. In addition, T-cell receptor (TCR) variable alpha- and beta
      chain mRNA expression was analyzed by polymerase chain reaction (PCR). The small
      cells stained faintly with anti-CD5 in two specimens, but were negative for the T
      cell specific markers, CD2, CD3, CD7, and CD8. In addition, these cells were
      weakly positive for CD11b (Mac-1) and CD54 (ICAM-1), but were negative for
      lymphocyte-specific CD11a (LFA-1) and CD11c (p150,95). No TCR V alpha or V beta
      gene expression was detected by PCR within these germinoma specimens. The small
      cells of germinomas with the cytologic appearance of lymphocytes are not derived
      from T-cells or other lymphocytic lineages.

PMID- 7736455
TI  - Role of beta-carotene on the changes in activity patterns and levels of
      biotransforming enzymes in transplantable murine lymphoma.
AB  - The differential levels of induction of hepatic microsomal cytochrome P-450 (cyt.
      P-450), UDP-glucuronyl transferase (UDPGT) and cytosolic glutathione-S
      transferase (GST) activities were evaluated over various periods of time,
      following tumor transplantation in male Swiss albino mice in the presence and
      absence of beta-carotene supplementation in their basal diet (100 mg/kg). An
      increase in the total hepatic microsomal cytochrome P-450 and UDP-glucuronyl
      transferase and cytosolic GSH-transferase activities (1.5 to 2 fold) occurred
      during the later stage of tumor progression (22 +/- 2 days onwards). However,
      beta-carotene supplementation throughout the study increased or decreased the
      random activity trends of the above markers significantly (P < 0.05- < 0.01).
      Finally, beta-carotene supplementation could enhance the survival of the host
      bearing lymphoma by almost 2-fold (50-60 days) over and above the lymphoma
      controls (30-35 days).

PMID- 7736456
TI  - Effects of okadaic acid and vanadate on TPA-induced monocytic differentiation in
      human promyelocytic leukemia cell line HL-60.
AB  - Treatment of HL-60 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) (1-5 nM)
      induced inhibition of cell growth and the appearance of an adherent monocyte-like
      cell type in a dose- and time-dependent manner. The extent of TPA-induced
      monocytic differentiation was found to be markedly reduced by okadaic acid (OA)
      (35 nM). OA had to be present for the early 12 h during treatment with TPA to
      reduce the induction of monocytic differentiation. The majority of cells (80%)
      were non-adherent but morphologically resembled mature myelocytes or granulocytes
      after treatment with TPA (5 nM) in the presence of OA (35 nM). Vanadate (VD), on
      the other hand, enhanced the extent of monocytic differentiation induced by low
      dose of TPA (1 nM). These results indicated that dephosphorylation by tyrosine
      protein phosphatase and serine-threonine protein phosphatase may play an
      important role in the induction of monocytic and granulocytic differentiation.

PMID- 7736457
TI  - In vivo exposure of rats to a weak alternating magnetic field increases ornithine
      decarboxylase activity in the mammary gland by a similar extent as the carcinogen
      DMBA.
AB  - Magnetic field (MF) exposure has been discussed in the process of tumor promotion
      as indicated by epidemiologic data as well as laboratory studies. However, the
      precise mechanisms of tumor promoting effects of MFs are unknown. Tumor promotion
      is often accompanied by an increase in the activity of the enzyme ornithine
      decarboxylase (ODC), i.e. a key enzyme in the biosynthesis of polyamines, which
      have roles in cell proliferation and control of gene expression. In the present
      work, we studied if exposure of female rats to a 50-Hz MF with a flux density of
      50 microT influences ODC activity in different tissues, including the mamma. Rats
      were exposed for a period of 6 weeks either with or without oral administration
      of the chemical carcinogen DMBA and all data were compared with those from sham
      exposed controls. Magnetic field exposure resulted in an approximate doubling of
      ODC in mammary tissue. A significant ODC increase was also seen in the spleen,
      but not in the liver, small intestine, bone marrow, and ear skin. The ODC
      increase produced by MF exposure in the mammae was of similar magnitude as that
      observed after treatment with DMBA. Combined treatment with MF and DMBA was not
      more effective in increasing ODC than treatment with DMBA alone, except for liver
      tissue. The present results on in vivo increases of ODC by MF exposure strengthen
      the hypothesis that weak 50-Hz MFs affect ODC activity and may thus function as a
      tumor-promoting or co-promoting agent.

PMID- 7736458
TI  - In vivo binding of diethylstilbestrol to nuclear proteins of kidneys of Syrian
      hamsters.
AB  - We demonstrate here that stilbene estrogen (diethylstilbestrol) is converted to
      nuclear protein binding metabolite(s) both in vitro and in vivo. In vitro
      reaction of DES with nuclei from hamster liver or kidney in the presence of
      cumene hydroperoxide or NADPH revealed binding of [3H]DES in nuclear proteins
      (histones; nonhistones precipitable by 2% TCA, NH2; nonhistones soluble in 2%
      TCA, NH30). The binding was significantly inhibited by cytochromes P450
      inhibitors. In an in vitro system [3H]DES quinone, one of the metabolites of DES,
      was able to bind to pure nonhistone proteins RNA polymerase and DNA polymerase.
      The binding of [3H]DES quinone to nonhistones RNA polymerase and DNA polymerase
      was inhibited by low molecular weight thiols, i.e. glutathione and cysteine, or
      thiol modifiers, such as n-ethylmaleimide, dithionitrobenzoic acid and
      hydroxymercuric benzoate. DES and DES metabolites inhibited transcriptional
      activity. In vivo [3H]DES was able to bind to nuclear proteins of hamster liver,
      kidneys and testes. The level of in vivo [3H]DES binding to all three types of
      nuclear proteins (histones, NH2, NH30) in the kidney (target organ) was two or
      more fold higher than that observed in the liver or testis (nontarget organs).
      Four nuclear NH30 proteins (mol wts.: 56, 37, 33 and 28 kDa) were irreversibly
      bound to [3H]DES in vivo. The in vivo binding of [3H]DES to transcriptionally
      active chromatin NH30 proteins also was observed. The data reported here
      establish that DES was able to bind to liver or kidney nuclear proteins in vitro,
      which was catalyzed by nuclear enzymes when fortified with an appropriate
      cofactor. DES quinone may be one of the protein binding metabolites. DES and DES
      metabolites inhibited transcriptional activity. The level of in vivo binding of
      [3H] DES to nuclear proteins of kidney (target organ) was double in comparison
      with that observed in liver or testis (nontarget organs). In vivo modifications
      in the chromatin proteins may be a factor in the development of DES-induced renal
      carcinogenesis is not clear.

PMID- 7736459
TI  - Induction of differentiation in murine erythroleukemia cells by 1 alpha,25
      dihydroxy vitamin D3.
AB  - The Friend murine erythroleukemia (MEL) cells can be stimulated to differentiate
      in response to a variety of chemical inducing agents. In the present study, the
      effect of 1 alpha,25-dihydroxyvitamin D3 on differentiation of MEL cells was
      investigated. Vitamin D3 induced differentiation of MEL cells in culture as
      determined by elevated hemoglobin content, a rise in the number of benzidine
      positive cells and increase in acetylcholine esterase activity. The optimum
      concentration of the vitamin required to induce differentiation of MEL cells was
      found to be 750 nM. The pattern of induction of differentiation was similar to
      that observed with DMSO and the induction of differentiation by vitamin D3 was
      inhibited by dexamethasone.

PMID- 7736460
TI  - Cyclo-glycosylation of a (1-->4)-linked glycooctaose and glycodecaose: synthesis
      of cyclo-lactooctaose and cyclo-lactodecaose.

PMID- 7736461
TI  - The specificity of the binding site of AchatininH, a sialic acid-binding lectin
      from Achatina fulica.
AB  - A sialic acid-binding lectin, AchatininH (ATNH), having unique specificity
      towards 9-O-acetylneuraminic acid, has been purified and characterized. The
      specificity of this lectin for O-acetylsialic acids was studied in detail, using
      various sialic acid derivatives and sialoglycoproteins. The potent inhibition of
      hemagglutination by bovine submaxillary mucin (BSM), which contains 9(7,8)-O
      acetylsialic acid and by free 9-O-acetylneuraminic acid confirms the preferential
      affinity towards this sugar. Further support for the role of O-acetylsialic acid
      was obtained by sialidase treatment of BSM. O-Deacetylation of the sialic acid
      residue abolished its inhibitory potency. Moreover, when the trihydroxypropyl
      side chain of the sialic acid molecule was modified by periodate-borohydride
      treatment, the truncated C7-sialic acid was unable to bind ATNH. This result
      suggests that the glycerol side chain of Neu5Ac, especially the C-8 and/or C-9
      portion is an important determinant for ATNH. The hemagglutination-inhibition
      results using several mono-, di-, and tri-saccharides containing terminal sialic
      acid and various sialoglycoproteins reveals that ATNH preferentially binds the
      alpha-(2-->6)-linked sialic acid. Furthermore, beta-D-GlcNAc-(1-->3)-[alpha-NeuGc
      (2-->6)]-GalNAc-ol was found to be the best ligand for ATNH.

PMID- 7736462
TI  - Anomalous Zemplen deacylation of protected methyl 2-deoxy-alpha-D-arabino-
      hexopyranosides and related methyl alpha-isomaltosides and alpha
      isomaltotriosides.

PMID- 7736463
TI  - Analysis of endo-(1-->5)-alpha-L-arabinanase degradation patterns of linear (1-
      >5)-alpha-L-arabino-oligosaccharides by high-performance anion-exchange
      chromatography with pulsed amperometric detection.

PMID- 7736464
TI  - Synthesis of the glycosyl amino acids N alpha-Fmoc-Ser[Ac4-beta-D-Galp-(1-->3)
      Ac2-alpha-D-GalN3p]-OPfp and N alpha-Fmoc-Thr[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D
      GalN3p]-OPfp and the application in the solid-phase peptide synthesis of multiply
      glycosylated mucin peptides with Tn and T antigenic structures.
AB  - Two new glycosyl amino acids N alpha-Fmoc-Ser[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D
      GalN3p]-+ ++OPfp and N alpha-Fmoc-Thr[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]
      + ++OPfp were synthesized. Glycosylation of N alpha-Fmoc-Ser-OPfp or N alpha-Fmoc
      Thr-OPfp with protected beta-D-Gal-(1-->3)-D-GalN3 donors afforded the glycosyl
      amino acids containing an activated C-terminus which could be utilized directly
      for solid-phase glycopeptide synthesis. The transformation of the 2-azido group
      into the acetamido derivative was achieved quantitatively at the end of the
      synthesis by treatment of the polymer-bound glycopeptide with thioacetic acid.
      The versatility of this strategy was demonstrated by the assembly of eight triply
      glycosylated mucin peptides which were synthesized simultaneously by multiple
      column techniques. The glycopeptides were prepared in order to investigate the
      substrate specificity of a galactosyltransferase.

PMID- 7736465
TI  - Synthesis of methyl glycosides of some alpha-isomalto oligosaccharides
      specifically deoxygenated at position C-2.
AB  - Methyl alpha-isomaltoside and methyl alpha-isomaltotrioside analogues
      specifically deoxygenated at position C-2 of various glucopyranosyl units were
      synthesized by condensation of either 6-O-acetyl-3-O-benzoyl-4-O-benzyl-1-O-tert
      butyldimethylsilyl-2-deoxy- beta-D-arabino-hexopyranose (trimethylsilyl triflate
      mediated) or 6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-glucopyranosyl chloride
      (mediated by silver carbonate and silver triflate) with suitably blocked
      derivatives of methyl alpha-D-glucopyranoside, its 2-deoxy analogue, or methyl 2'
      deoxy-alpha-isomaltoside.

PMID- 7736466
TI  - The reaction between epichlorohydrin and polysaccharides: Part 2, Synthesis of
      some model substances, with cyclic substituents.
AB  - Eight derivatives of methyl alpha-D-glucopyranoside, in which the substituents
      are part of cyclic structures, have been prepared as model substances for
      possible structural elements formed on reaction of polysaccharides with
      epichlorohydrin. The substances were converted into the permethylated alditol-1-d
      acetates and characterised by CIMS and EIMS.

PMID- 7736467
TI  - Isothiocyanates and cyclic thiocarbamates of alpha,alpha'-trehalose, sucrose, and
      cyclomaltooligosaccharides.
AB  - 6,6'-Dideoxy-6,6'-diisothiocyanato-alpha,alpha'-trehalose (4), 6-deoxy-6
      isothiocyanato-alpha-D-fructo-furanose beta-D-fructopyranose 1,2':2,1'
      dianhydride (11), 6,6'-dideoxy-6,6'-diisothiocyanatosucrose (16), and per(6-deoxy
      6-isothiocyanato)-cyclomaltohexaose (23), -cyclomaltoheptaose (27), and 
      cyclomaltooctaose (31) have been prepared in high yield by reaction of the
      corresponding amino sugars with thiophosgene. In the absence of base, all
      isothiocyanates were stable and could be stored and acetylated without
      decomposition. In the presence of triethylamine, 6,6'-dideoxy-6,6'
      diisothiocyanato-alpha,alpha'-trehalose underwent intramolecular cyclisation
      involving HO-4 to give the corresponding bis(cyclic thiocarbamate). The product
      of cyclisation at a single glucopyranosyl unit was obtained in the treatment of
      the above diisothiocyanate with mixed (H+, HO-) ion-exchange resin. Under
      identical reaction conditions, 6,6'-dideoxy-6,6'-diisothiocyanatosucrose yielded
      exclusively the product of intramolecular cyclisation at the D-glucopyranosyl
      moiety, while derivatives of alpha-D-fructofuranose beta-D-fructopyranose
      1,2':2,1'-dianhydride and cyclomaltooligosaccharides remained unchanged.

PMID- 7736468
TI  - Dynamics in aqueous solutions of the pentasaccharide corresponding to the binding
      site of heparin for antithrombin III studied by NMR relaxation measurements.
AB  - 1H NMR and 13C NMR relaxation measurements at different magnetic field strengths
      were used to study the nature of overall and internal motions, in aqueous
      solution, of the synthetic pentasaccharide (A-G-A*-I-AM) corresponding to the
      binding site of heparin for antithrombin III. Two-dimensional double INEPT
      spectra were recorded at 11.7 T with and without suppression of cross-correlation
      effects between dipolar and chemical shift anisotropy relaxation mechanisms in
      measurements of spin-lattice and spin-spin relaxation times. Moreover,
      longitudinal relaxation times were collected at 7 T with the inversion recovery
      method. One dimensional NOESY spectra were recorded at 11.7 T and 9.4 T with
      various mixing times when spins of the A1* and A4* protons were inverted in the
      central residue of the pentasaccharide. Differences in the T1 relaxation times,
      as well as in the cross-relaxation rates between protons relaxing through fixed
      distances in the A* residue, indicated that the molecule tumbles anisotropically
      in solution. However, in order to achieve agreement between the spectral and the
      model data, the presence of internal motions had to be also considered, in
      addition to the assumption of a symmetric top model for the description of
      overall tumbling. The changes in the longitudinal and transversal relaxation
      times, collected with and without suppression of interference effects, supported
      the assumption that the cross-correlation between dipolar and chemical shift
      anisotropy relaxation mechanisms cannot be neglected in this medium-sized
      molecule. In fact, the influence of these effects was 10-15% in T1 and 20-25% in
      T2 relaxation times. The experimental data were analyzed using model free
      formalism and the computed order parameters indicate a decrease in spatial
      restriction from the central residue (S2 approximately 0.9) towards both ends of
      the pentasaccharide (S2 approximately 0.7). The anisotropy ratio found was
      approximately 3.3 with correlation times tau parallel = 450 ps and tau
      perpendicular = 1480 ps. The values of effective correlation time were within the
      range of tens of picoseconds. Thus, for a more precise interpretation of the
      experimental data for the pentasaccharide, in addition to internal motions and
      anisotropic tumbling, the effect of cross-correlation must be taken into account
      as well.

PMID- 7736469
TI  - Stereoselective thermal transfer of fructose from sucrose to cyclodextrins.
AB  - Branched cyclodextrins (CDs) have been formed by the thermal transfer of a
      fructosyl group from sucrose to O-6 of one of the glucose residues of
      cyclomaltohexa- and hepta-ose (alpha-CD and beta-CD). In each case the fructosyl
      group adds almost entirely in the beta configuration. The resultant
      fructosylcyclodextrins (Fru-CDs) show increased solubility in water and, in the
      case of Fru-beta-CD increased ability to solubilize sparingly soluble compounds
      by inclusion, relative to the parent cyclodextrins. However, the Fru-CDs have
      similar abilities to form complexes as their respective parent CDs. Fru-CDs act
      as inhibitors of invertase.

PMID- 7736470
TI  - Structural analysis of the polysaccharide from Pachymenia lusoria
      (Cryptonemiaceae, Rhodophyta).
AB  - The highly complex polysaccharide extracted from the New Zealand red alga
      Pachymenia lusoria (Grev.) J. Ag. has been characterised and certain structural
      features defined. A reductive hydrolysis procedure was used for constituent sugar
      and linkage analyses, with trideuteriomethylation being employed to enable the
      location of natural methyl ether groups to be determined. A reductive partial
      hydrolysis procedure allowed agarobiosyl constituent residues to be identified.
      The analytical results are consistent with the polymer having a linear backbone
      of 3-linked D-galactopyranosyl alternating with 4-linked D- or L-galactopyranosyl
      residues. The 3-linked residues are nearly all 2-sulfated, with 1 in 3 also being
      6-O-methylated and 1 in 5 also bearing a 4,6-pyruvic acetal residue. About one
      third of the polymer is comprised of blocks of agarobiosyl repeat units that are
      2-sulfated on the beta-D-galactopyranosyl and one-third 2-O-methylated on the 3,6
      anhydro-L-galactosyl constituents. Of the remaining 4-linked residues, half are 2
      O-methyl-D-galactopyranosyl residues and half are galactopyranosyl residues, of
      which approximately half are in the L configuration.

PMID- 7736471
TI  - Subsite mapping of porcine pancreatic alpha-amylase I and II using 4-nitrophenyl
      alpha-maltooligosaccharides.
AB  - The catalytic efficiency (kcat/Km) and the cleaved bond distribution for the
      nitrophenylated maltooligosaccharides, p-NPGlcn (2 < or = n < or = 7) hydrolysed
      by porcine pancreatic alpha-amylase isozymes I and II were determined. The
      subsite affinities (Ai) were calculated from the p-NPGlcn (4 < or = n < or = 7)
      hydrolysis data. Five subsites (-3 to 2) bind glucosidic residues with a positive
      affinity. No additional subsites could be detected both at the reducing end (3,
      4, 5) and at the nonreducing end (-4, -5, -6). The energetic profiles of both
      isozymes are similar. The energetic profile of PPA differs from other alpha
      amylases by having both a small number of subsites, and a catalytic subsite with
      a high positive affinity. Excellent agreement was found between observed
      catalytic efficiency values and those calculated from the subsite affinities.

PMID- 7736472
TI  - Synthesis of isomeric sulfated disaccharides. Methyl O-(2-acetamido-2-deoxy-3-O-,
      4-O-, and 6-O-sulfo-beta-D-glucopyranosyl sodium salt)-(1-->3)-beta-D
      galactopyranoside.

PMID- 7736473
TI  - The core trisaccharide of alpha-L-arabinofuranan: synthesis of methyl 3,5-di-O
      alpha-L-arabinofuranosyl-alpha-L-arabinofuranoside.

PMID- 7736474
TI  - Disialyl lactose from buffalo colostrum: isolation and characterization.

PMID- 7736475
TI  - [Body fluid withdrawal with isolated ultrafiltration effects persistent
      improvement of functional capacity in patients with chronic congestive heart
      failure. Furosemide does not produce the same result].
AB  - In moderate congestive heart failure pulmonary overhydration may be detected at
      chest X-ray even if therapy is optimized to keep the urinary output normal and to
      prevent weight gain and dependent edema formation. Removal of overhydration of
      the lung may help to define its significance. This study was aimed at
      investigating whether a subclinical accumulation of fluid in the lung
      interstitium in moderate congestive heart failure interferes with the patient's
      functional capacity, and whether furosemide is able to promote reabsorption of
      the excessive fluid. Patients whose digoxin, oral furosemide and ACE-inhibitor
      therapeutic regimen was kept constant, were randomly allocated to ultrafiltration
      (8 cases) or iv bolus (mean dose = 248 mg) of supplemental furosemide (8 cases).
      The amount of body fluid removed with each method approximated 1.600 ml.
      Functional performance was assessed with cardiopulmonary exercise tests. Soon
      after fluid withdrawal with either procedure the filling pressures of the two
      ventricles and body weight were reduced and plasma renin activity, norepinephrine
      and aldosterone were augmented. After furosemide hormones remained elevated in
      the subsequent 4 days, and, during this period, patients had positive water
      metabolism, recovery of the elevated ventricular filling pressures, recurrence of
      lung congestion without any improvement in functional capacity. In ultrafiltrated
      patients, renin, norepinephrine and aldosterone fell below control values within
      the first 48 hours and water metabolism was equilibrated at a new set point (less
      fluid intake and diuresis without weight gain). Functional capacity in these
      patients was improved through favorable circulatory and ventilatory adjustments
      consequent on reabsorption of lung water. This may also have restored the ability
      of the lung to clear norepinephrine, thus restraining its facilitation of renin
      release. Improvement persisted at 3 months after the procedure. In congestive
      heart failure the set point of fluid balance is altered despite oral furosemide;
      supplemental iv furosemide does not shift the set point, at least in the presence
      of ACE-inhibition; excessive, although silent, lung water limits the functional
      capacity of the patient.

PMID- 7736476
TI  - [Does coexistence of involvement of the right dominant coronary artery
      differentiate clinical features of disease of the common trunk from disease of 3
      coronary vessels?].
AB  - We have studied clinical and ECG stress features of 119 patients with left main
      disease and 113 matched patients with three vessels coronary disease. Clinical
      features and ECG stress test do not differentiate the two groups as a whole.
      Exercise time duration was shorter, ST criteria were more positive, and peak
      heart rate was lower in the subgroups of patients with left main and involvement
      of a right dominant coronary artery. However due to a large overlap these
      criteria do not seem to be clinically useful. In conclusion, in an individual
      patient angina and stress ECG criteria do not differentiate the patients with
      left main from those with three vessels coronary artery disease.

PMID- 7736477
TI  - [Infectious endocarditis in dentistry practice: recent controversies and modes of
      the use of antibiotic prophylaxis].
AB  - A survey by questionnaire to assess the daily practice of the antibiotic
      prophylaxis of infective endocarditis by physicians attending post-graduate
      schools of the Institutes of Oral Surgery and Stomatology (Group A n = 83) and
      Cardiology (Group B n = 46) of the Second University of Naples has been
      conducted. They were asked about dental procedure and cardiopathies that require
      prophylaxis for infective endocarditis, the relationship between infective
      endocarditis and rheumatic disease and the provision of antibiotic. Extraction of
      tooth and dental and oral surgery have been reported as the most risky
      procedures. Moreover provision of antibiotic prophylaxis was suggested to
      patients not at risk (pacemaker or coronary artery bypass), and was not suggested
      in high risk conditions (mitral valve prolapse with regurgitation and
      hypertrophic cardiomyopathy). Most of the 50-60% practitioners usually start the
      prophylaxis 24-48 hours before the procedure and prolong it for 48-72 hours.
      These results underline the need for improvement of the knowledge for the
      antibiotic prophylaxis of infective endocarditis.

PMID- 7736478
TI  - [Echocardiography in the early diagnosis of acute rejection in patients with
      heart transplant].
AB  - The aim of our study was to assess the sensibility and specificity of Doppler
      echocardiographic evaluation of left ventricular diastolic function during acute
      cardiac rejection. We studied 34 patients who had undergone a recent heart
      transplant and compared the echocardiographic results with the histologic
      findings. We considered the following parameters of left ventricular filling:
      early peak of mitral flow velocity; pressure half-time (PHT); isovolumic
      relaxation time (IVRT). We divided the patients into two groups according to the
      histologic findings: Group I (25 patients who had at least 1 episode of mild
      moderate rejection), Group II (6 patients without documented rejection after at
      least three consecutive biopsies). Three patients with clinically evident
      rejection were excluded from the analysis. In Group I cardiac rejection was
      associated with a statistically significant decrease in IVRT (p < 0.0005),
      without significant changes in heart rate and in the early peak of mitral flow
      velocity. In Group II Doppler parameters remained unchanged. These variations
      were not associated with changes in echocardiographic morphologic parameters and
      in parameters of ventricular systolic function. IVRT and PHT returned to normal
      values after adequate immunosuppressive treatment. Considering variations of IVRT
      and PHT of at least 20%, we obtained a sensibility of 88% for isolated variations
      of PHT and a specificity of 93% for consensual variations of PHT and IVRT.
      Therefore, the assessment of the left ventricular diastolic function by Doppler
      echocardiography represents a safe and non-invasive method for an early detection
      of acute cardiac rejection.

PMID- 7736479
TI  - [Cardiovascular changes secondary to therapeutic irradiation of the mediastinum].

PMID- 7736480
TI  - [Ambulatory monitoring of arterial pressure in the diagnosis and therapeutic
      evaluation of dysautonomic diseases: observations in a case of Shy-Drager
      syndrome].
AB  - Shy-Drager syndrome is a very rare disease affecting the autonomic nervous
      system. Usefulness of beta-adrenergic chronic therapy has already been focused in
      these cases. Ambulatory blood pressure monitoring may help to study the
      cardiocirculatory adaptation in Shy-Drager syndrome patients.

PMID- 7736481
TI  - [Left cor triatriatum in a man over 60].
AB  - A case of cor triatriatum in a 66-year-old man is reported. The patient died of
      pneumonia; ante mortem diagnosis was made with both transthoracic and
      transesophageal echocardiography. Autopsy finding showed a very good correlation
      between anatomical and echocardiographic abnormalities. Cor triatriatum is
      amenable to surgical correction and echocardiography is extremely helpful in the
      diagnosis.

PMID- 7736482
TI  - Prognostic implications of asymptomatic cardiac ischemia.
AB  - The Oslo Ischemia Study was initiated between 1972 and 1975 in 2,014 men (age, 40
      59 years), with the aim of detecting previously unknown and unsuspected coronary
      heart disease. Of the men who were eligible, 86% participated and were apparently
      free from cardiovascular disorders. Following a positive symptom-limiting bicycle
      test, 109 of the men underwent diagnostic coronary angiography and 105 were
      evaluable; the angiograms were normal in 36 and pathologic in 69. Nineteen of the
      men with pathologic angiograms had mild angina on the exercise test, while 50
      (72%; 2.5% of total study population) remained completely asymptomatic. During a
      mean follow up of 15 years, 14 of the 50 completely asymptomatic men died (12
      suddenly, 1 of whom had angina pectoris for 5 years). Eighteen of the surviving
      36 men remained completely asymptomatic and free from signs of coronary artery
      disease, other than exercise-induced ST-segment depression. One man had ECG signs
      of a previous myocardial infarction, on the annual follow up; chest pain as a
      first presenting symptom was observed in a further 17 of 36 survivors. Repeat
      angiography was performed in 22 men who experienced either chest pain or
      worsening symptoms following exercise test; of these, 14 underwent coronary
      bypass surgery and are still alive. The data appear to refute a 'wait-and-see'
      policy among subjects with asymptomatic cardiac ischemia.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7736483
TI  - Hypertension and silent myocardial ischemia: their influence on cardiovascular
      mortality and morbidity.
AB  - The presence of ST-segment depression during ambulatory electrocardiographic
      monitoring, in relation to blood pressure treatment and control, was monitored in
      a non-randomized study in 167 men (49%) from the 'Men born in 1914' Malmo study,
      who were considered to have hypertension (diastolic blood pressure [DBP], > or =
      95 mm Hg or receiving antihypertensive therapy). Men were excluded if they had a
      history of ischemic heart disease. A high frequency of ST-segment depression
      (41%) and associated high cardiac event rate (14%) were found in hypertensive
      elderly men who had inadequately controlled blood pressure (i.e. DBP > or = 95 mm
      Hg). This was associated with a relative risk of a cardiac event of 9.8 (95%
      confidence interval: 2.6-36.9), even after adjustment for smoking, blood lipids
      and alcohol consumption. The lower frequency of ST-segment depression (21%) and
      lower cardiac event rate (5%) in hypertensive men with adequate blood pressure
      control suggests that effective antihypertensive treatment leads to a reduced
      event rate. In conclusion, the occurrence of ST-segment depression during
      ambulatory electrocardiographic monitoring in this group of subjects may be an
      expression of silent myocardial ischemia, with or without left ventricular
      hypertrophy. The incidence of asymptomatic ST-segment depression and the rate of
      cardiac events in hypertensive patients may be, in part, related to the level of
      blood pressure control attained.

PMID- 7736484
TI  - Amlodipine and the total ischemic burden: circadian anti-ischemia program in
      Europe (CAPE) trial-methodology, safety and toleration. The Steering Committee
      members and all of the investigators.
AB  - The Circadian Anti-Ischemic Program in Europe (CAPE) trial was a large,
      multinational trial, taking place in ten countries and involving over 100
      investigators. It was a double-blind, parallel, randomized, placebo-controlled
      trial comparing once-daily amlodipine with placebo in chronic stable angina
      pectoris. It consisted of two phases, the first being a 2-week, single-blind,
      placebo run-in phase during which stable doses of anti-anginal drugs were
      maintained (65% of patients were receiving beta-blockers), and the second an 8
      week active treatment phase in which patients received either amlodipine or
      placebo, 5 mg once daily, for the first 4 weeks, increasing to 10 mg once daily
      for the second 4 weeks. Patients were randomized in a ratio of 2 patients
      receiving amlodipine to each patient receiving placebo. Out of an initial 1,160
      patients screened, 315 entered the study, with 250 having complete efficacy
      evaluable data. Patients were included if they experienced > or = 4 ambulatory
      ECG ischemic episodes (> or = 1 mm ST-segment depression for > or = 1 min) and/or
      > or = 20 min total ischemia time over 48 h. Data were obtained on the total
      frequency of ST-segment depression events, the ischemia area (ST-segment
      depression integral), the ischemic time and peak ST-segment depression. Patient
      diary information on angina attack rate and nitroglycerin tablet consumption was
      also collected. Patients in both groups were compared for age, blood pressure,
      heart rate, duration of angina and baseline ischemia at entry. Amlodipine and
      placebo had similar safety profiles, with 17.3% of amlodipine patients recording
      adverse events, compared with 13.3% of placebo patients.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7736485
TI  - Circadian variation and triggers of cardiovascular disease.
AB  - It has recently been shown that approximately 90% of cases of non-fatal
      myocardial infarction and many cases of sudden cardiac death are caused by
      disruption of a coronary atherosclerotic plaque, followed by occlusive thrombus
      formation. Secondly, the circadian pattern of myocardial infarction is well known
      to feature a prominent increase in the morning hours. Taken together, these
      factors may provide an opportunity to reduce deaths caused by cardiovascular
      disease. Findings indicate that, in many cases, plaque disruption and thrombus
      formation are triggered by the activities of the patient. It is postulated that
      onset occurs when a 'vulnerable' atherosclerotic plaque becomes disrupted and
      occlusive thrombus formation occurs. The occurrence of a myocardial infarction in
      the morning hours could result from the synchronization of a number of potential
      triggers. The importance of the recognition of the circadian variation of acute
      onset of myocardial infarction is that pharmacologic protection can be directed
      at the early waking hours. It would seem reasonable to propose that long-acting
      anti-ischemic agents would have an advantage over short-acting agents in
      providing protection against the morning occurrence of myocardial infarction. A
      future goal would be to design therapeutic regimens that would have the ability
      to sever the linkage between a potential triggering activity and the development
      of myocardial infarction.

PMID- 7736486
TI  - Special issue: Spotlight on the Na/H exchanger.

PMID- 7736487
TI  - Structure-function studies and molecular regulation of the growth factor
      activatable sodium-hydrogen exchanger (NHE-1).

PMID- 7736488
TI  - Molecular biology of the cardiac sodium/hydrogen exchanger.

PMID- 7736489
TI  - Regulation of platelet function by sodium-hydrogen exchange.

PMID- 7736490
TI  - Aldosterone specific membrane receptors, rapid activation of the sodium-hydrogen
      exchanger, and cardiovascular implications.
AB  - Functional studies in extrarenal non-epithelial cells such as smooth muscle cells
      and easily accessible human lymphocytes have demonstrated that aldosterone not
      only produces classical genomic effects, but also rapid non-genomic effects on
      transmembrane electrolyte movements. These involve the activation of the Na+/H+
      exchanger of the cell membrane at very low, physiological concentrations of
      aldosterone with an acute onset within one to two minutes. They cannot therefore
      be explained by genomic mechanisms which appear to succeed the membrane related
      rapid responses as late effects. The mechanisms underlying these fast aldosterone
      electrolyte effects have been studied extensively in human lymphocytes and rat
      vascular smooth muscle cells representing attractively valuable tools in the
      delineation of the receptor-effector mechanisms involved. This includes the
      demonstration of membrane binding sites in lymphocytes which are highly specific
      for aldosterone and transmit the rapid non-genomic responses to aldosterone, as
      suggested by the intriguing similarities of binding kinetics and pharmacology in
      the receptor and effector assays. The unique characteristics of this new pathway
      for steroid action includes its rapid time course, 10,000-fold selectivity for
      aldosterone over cortisol, and the ineffectiveness of spironolactones, the
      classical mineralocorticoid antagonists. The two step model for the membrane
      action of mineralocorticoids developed here shares many features with that
      developed for other steroid hormones, for example on their neural activity. Since
      not only lymphocytes but also vascular smooth muscle cells are equipped with the
      rapid aldosterone effector mechanism, this new model may become the basis for the
      developing concept of steroids as regulators of cardiovascular functions.

PMID- 7736491
TI  - Regulation of sodium-hydrogen exchange in vascular smooth muscle.
AB  - The Na+/H+ exchanger in vascular smooth muscle cells represents a major mechanism
      for sodium influx and is also one of the principal mechanisms responsible for the
      regulation of intracellular pH (pHi). In this review, the relationship between
      pHi and vascular smooth muscle cell growth, the regulation of Na+/H+ exchange by
      vasoactive agents and growth factors, and the second messenger pathways that may
      be involved in activation of Na+/H+ exchange have been discussed. The exchanger
      appears to be important in vascular smooth muscle cell growth, based on results
      that (1) Na+/H+ exchange is stimulated by hypertrophic and hyperplastic agonists,
      (2) vascular smooth muscle cell proliferation is induced by cytoplasmic
      alkalinisation in the absence of mitogens, (3) vascular smooth muscle cell
      proliferation is dependent on extracellular sodium, and (4) inhibitors of Na+/H+
      exchange block cell growth. Several pathways appear capable of activating the
      exchanger in vascular smooth muscle cells as there is evidence for both calcium
      and protein kinase C dependent and independent pathways. We speculate that the
      calcium and protein kinase C dependent pathways may play a role in the
      contractile response of differentiated vascular smooth muscle cells in the vessel
      wall, while the calcium and protein kinase C independent pathways may be involved
      in the proliferative response observed after arterial injury and in tissue
      culture.

PMID- 7736492
TI  - Neurohumoral modulation of intracellular pH in the heart.

PMID- 7736493
TI  - Potential of selective sodium-hydrogen exchange inhibitors in cardiovascular
      therapy.

PMID- 7736494
TI  - Clinical and in vivo antiarrhythmic potential of sodium-hydrogen exchange
      inhibitors.
AB  - Intracellular acidification may be the initial stimulus for a cascade of events
      contributing to intracellular calcium overload. Ischaemia results in the
      accumulation of lactate and other proton donors causing intracellular
      acidification. During reperfusion the activity of the Na+/H+ exchanger recovers,
      allowing extrusion of protons at the expense of increases in intracellular
      sodium. The rise in intracellular sodium decreases the gradient required for
      sodium calcium exchange, resulting in accumulation of intracellular calcium.
      These data are in keeping with the pathophysiological model that the Na+/H+
      exchanger is an important part of a cascade leading from intracellular acidosis
      to intracellular sodium loading followed by calcium overload. From this model we
      predicted that amiloride would be antiarrhythmic. In 1988, we reported that low
      concentration of amiloride (0.1-0.3 microM) suppresses the induction of sustained
      ventricular tachyarrhythmias in dogs late following infarction. Amiloride
      suppressed inducible ventricular tachycardia in approximately 50% of the animals.
      In an extension of this work we assessed the efficacy of amiloride in suppressing
      inducible ventricular tachycardia in humans who presented with symptomatic
      ventricular tachycardia. In that study, amiloride manifested antiarrhythmic
      activity, but not to the degree that was observed in our dog model. Six of 31
      patients (19%) had complete suppression of induced ventricular tachycardia. In an
      extension of this work, we assessed in our in vivo dog model which of the
      pharmacological effects of amiloride were associated with antiarrhythmic
      efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736495
TI  - Methods of measuring intracellular pH in the heart.

PMID- 7736496
TI  - Induction of expression of the sodium-hydrogen exchanger in rat myocardium.
AB  - OBJECTIVE: The aim was to examine the regulation of the cardiac Na+/H+ exchanger
      NHE-1 isoform mRNA in response to ischaemia and acidosis in the mammalian
      myocardium. METHODS: Male Sprague Dawley rat hearts were perfused in a non
      circulated retrograde fashion according to the Langendorff method. Hearts were
      perfused for 3 h at flow rates of either 10 ml.min-1 (control), or 3, 1, or 0
      ml.min-1 (ischaemia) followed by 5 min of reperfusion. Hearts were immediately
      frozen in liquid N2, and stored at -80 degrees C until ready for RNA isolation.
      Northern blot analysis was used to examine expression of the NHE-1 isoform of the
      Na+/H+ exchanger message in these isolated perfused hearts. Activity of the
      Na+/H+ exchanger was assessed in primary cultures of neonatal rat myocytes under
      either control conditions or after treatment with chronic, low external pH.
      RESULTS: A decrease in developed tension and an increase in resting tension was
      observed which was dependent upon the severity of the ischaemic episode. Low flow
      ischaemia of 3 ml.min-1 caused increased Na+/H+ exchanger message levels, while
      perfusion at more reduced flow rates eliminated the increase. Treatment of
      primary cultures of isolated myocytes with low external pH resulted in increased
      ability to recover from an acute acid load. CONCLUSIONS: Low flow ischaemia can
      increase the Na+/H+ exchanger message in the intact mammalian myocardium. More
      severe ischaemia prevents the increase, suggesting that severely damaged tissue
      may not be capable of the ischaemic response. Primary cultures of isolated
      myocytes can respond to chronic low external pH by increasing Na+/H+ exchanger
      activity.

PMID- 7736497
TI  - Sodium-hydrogen exchange inhibitors improve postischemic recovery of function in
      the perfused rabbit heart.
AB  - OBJECTIVE: The aim was to examine the effects of the Na+/H+ exchange inhibitors
      amiloride and methylisobutyl amiloride (MIA) in buffer perfused rabbit hearts
      subjected to one hour of normothermic ischaemia (37 degrees C) followed by
      reperfusion. METHODS: Experiments were carried out in five groups of Langendorff
      perfused rabbit hearts: (1) control, (2) amiloride, and (3) MIA (agents in both
      the preischaemic and reperfusion perfusate), (4) amiloride-R and (5) MIA-R
      (agents added at reperfusion only). Functional evaluation included serial
      measurement of resting tension, force, rates of ventricular force development and
      relaxation, and coronary perfusion pressure. Samples of coronary effluent were
      obtained for creatine kinase assay and hearts were freeze clamped for metabolite
      assays. RESULTS: Reperfusion resulted in a marked increase in resting tension in
      group (1) which was statistically significant compared to groups (2) and (3).
      Groups (2) and (3) also showed significantly improved recovery of ventricular
      force, rate of force development, and rate of ventricular relaxation. Addition of
      either agent only during reperfusion failed to produce a significant beneficial
      effect. There were no significant differences among the groups with respect to
      postreperfusion creatine kinase release or end reperfusion metabolite levels.
      CONCLUSION: This study shows for the first time that both of the Na+/H+ exchange
      inhibitors amiloride and MIA produce improved recovery of ventricular function in
      rabbit hearts subjected to ischaemia and reperfusion, although the beneficial
      effect was not obtained with drug administration at the time of reperfusion only.

PMID- 7736498
TI  - Angiotensin II stimulates sodium-hydrogen exchange in adult rabbit ventricular
      myocytes.
AB  - OBJECTIVE: The aim was to characterise the effects of angiotensin II on Na+/H+
      exchange in adult ventricular myocytes. METHODS: Intracellular pH (pHi) was
      continuously measured with the fluorescent pH indicator, SNARF-1, in single
      resting myocytes obtained from adult rabbits by enzymatic dissociation. In some
      experiments cells were electrically paced to elicit contractions. All experiments
      were performed at 36 degrees C in HEPES buffered solution containing no added CO2
      or HCO3- (pHo 7.4). RESULTS: Rapid application of angiotensin II caused pHi to
      rise. The initial rate of rise and initial net H+ efflux responded to angiotensin
      II in a concentration dependent manner, EC50 = 7.8. Buffering of cytosolic
      calcium with the calcium chelator BAPTA did not affect the initial net H+ efflux
      elicited by 1 microM angiotensin II. The increase in steady state pHi was blocked
      by inhibitors of Na+/H+ exchange, amiloride (1 mM) and EIPA (10 microM).
      Angiotensin II also increased the rate of pHi recovery from intracellular
      acidosis at pHi values above approximately 6.9. During inhibition of Na+/H+
      exchange the application of angiotensin II decreased steady state pHi. This
      acidosis was blocked by preincubation in dextrose-free solution containing 20.0
      mM 2-deoxy-D-glucose and 10 microM EIPA. The positive inotropic effect of
      angiotensin II was markedly suppressed by amiloride. CONCLUSIONS: Angiotensin II
      exerts a concentration dependent stimulatory effect on Na+/H+ exchange in adult
      rabbit ventricular myocytes. This effect does not appear to involve changes in
      cytosolic calcium. During inhibition of Na+/H+ exchange, angiotensin II causes
      pHi to fall, perhaps by stimulating metabolic acid production. The positive
      inotropic action of angiotensin II depends, in part, on stimulation of Na+/H+
      exchange.

PMID- 7736499
TI  - Exacerbation of reperfusion arrhythmias by alpha 1 adrenergic stimulation: a
      potential role for receptor mediated activation of sarcolemmal sodium-hydrogen
      exchange.
AB  - OBJECTIVE: Stimulation of myocardial alpha 1 adrenoceptors causes (1)
      exacerbation of reperfusion induced arrhythmias, and (2) stimulation of
      sarcolemmal Na+/H+ exchange. The aims of this study were to identify the alpha 1
      adrenoceptor subtype involved in the former effect and to determine whether
      stimulation of the Na+/H+ exchanger may play a role in this phenomenon. METHODS:
      Isolated rat hearts were subjected to independent perfusion of the left and right
      coronary beds. After 15 min of aerobic perfusion of both beds, the alpha 1
      adrenoceptor agonist phenylephrine (0.1, 1, or 10 microM) was infused selectively
      into the left coronary bed for 2 min. The left coronary bed was then subjected to
      7 min of zero flow ischaemia and 5 min of reperfusion. RESULTS: The incidence of
      reperfusion induced ventricular fibrillation was increased from 0% in controls to
      8%, 42%*, and 75%* with 0.1, 1, and 10 microM phenylephrine (*P < 0.05); this
      dose dependent effect occurred in the absence of significant intergroup
      differences in vascular resistance or heart rate. Similar infusion of methoxamine
      at 10 microM also increased the incidence of reperfusion induced ventricular
      fibrillation from 13% to 88%*. Infusion of 10 microM phenylephrine during
      reperfusion alone did not affect the incidence of reperfusion induced ventricular
      fibrillation. Infusion of the selective alpha 1A adrenoceptor antagonist WB4101
      at 0.1, 1, or 10 microM for 2 min immediately before ischaemia (concomitantly
      with 10 microM phenylephrine) reduced the incidence of reperfusion induced
      ventricular fibrillation from 83% to 75%, 25%*, and 0%*. Similar infusion of the
      selective alpha 1B adrenoceptor antagonist chloroethylclonidine (0.1 or 1 microM)
      or the selective beta 1 adrenoceptor antagonist atenolol (0.1 or 1 microM) did
      not reduce the incidence of reperfusion induced ventricular fibrillation. The
      novel NHE-1 selective Na+/H+ exchange inhibitor HOE694 (10 microM), when infused
      into the left coronary bed before ischaemia (concomitantly with 10 microM
      phenylephrine) and throughout reperfusion, reduced the incidence of reperfusion
      induced ventricular fibrillation from 83% to 25%*. In hearts that received 10
      microM phenylephrine before ischaemia. HOE694 (10 microM) was partially effective
      when infused during reperfusion alone (ventricular fibrillation incidence reduced
      from 83% to 42%). CONCLUSIONS: (1) the exacerbation of reperfusion induced
      arrhythmias by alpha 1 adrenergic stimulation during ischaemia is mediated by the
      alpha 1A adrenoceptor subtype, and (2) increased Na+/H+ exchanger activity during
      ischaemia and reperfusion may play a causal role in this phenomenon.

PMID- 7736500
TI  - Hypercapnic acidosis and dimethyl amiloride reduce reperfusion induced cell death
      in ischaemic ventricular myocardium.
AB  - OBJECTIVE: The aim was to investigate the effects of slowing the recovery of
      ischaemia induced intracellular acidosis with hypercapnic acidosis or dimethyl
      amiloride (DMA) on the extent of reperfusion induced cell death. METHODS:
      Isolated arterially perfused rabbit papillary muscles and septa were suspended in
      a controlled atmosphere and perfused with a modified Tyrode solution containing
      erythrocytes and trypan blue (500 microM). Ischaemia was produced by arrest of
      perfusion and withdrawal of atmospheric O2. Extracellular pH of the muscle during
      reperfusion was controlled by adjusting the pH of the perfusate (pH 6.6 or pH 7.6
      with and without DMA 20 microM) and changing the PCO2 of the chamber atmosphere.
      After 30 min of reperfusion following 30 min (group A) or 60 min (group B) of
      ischaemia, papillary muscles were fixed with paraformaldehyde. Cell death was
      assessed by trypan blue staining of nuclei in histological sections of the
      papillary muscles. RESULTS: The magnitude of cell death was greatest after
      reperfusion with pH 7.6 as measured by the percentage of nuclei staining with
      trypan blue (15.1% in group A; 41.8% in group B). By contrast, reperfusion at pH
      6.6 reduced cell killing (group A, 3.6%; group B, 7.2%). Reperfusion at pH 7.6
      with DMA (20 microM) also reduced trypan blue uptake (group A, 2.8%; group B,
      3.8%). Despite the attenuation of cell death afforded by acidosis or Na+/H+
      exchange inhibition, significant swelling of the extracellular space and
      microvascular injury was noted. CONCLUSIONS: Hypercapnic acidosis and Na+/H+
      exchange inhibition during reperfusion attenuate lethal reperfusion injury to
      ventricular myocardium and extend to the intact myocardium the concept of the "pH
      paradox" in which recovery of intracellular pH after reperfusion is a
      precipitating factor in lethal cell injury.

PMID- 7736501
TI  - Intracellular pH in vascular smooth muscle: regulation by sodium-hydrogen
      exchange and multiple sodium dependent HCO3- mechanisms.
AB  - OBJECTIVES: The aim was to determine the mechanisms, particularly bicarbonate
      dependent mechanisms, of intracellular pH (pHi) recovery from various acidoses in
      vascular smooth muscle and to explore the ATP dependency of the respective
      mechanisms. METHODS: Experiments were conducted in rat aortic smooth muscle cells
      grown in primary culture and synchronised in a non-growing state by serum
      deprivation. pHi was measured in cells loaded with the pH sensitive fluorescent
      dye, 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein (BCECF). Chloride
      efflux was studied by determination of the rate of efflux of 36Cl over 5 min.
      Cells were ATP depleted by substitution of glucose in the medium by 2
      deoxyglucose. Acidoses were induced by CO2 influx and NH3 efflux techniques.
      RESULTS: In the absence of HCO3-, the 5-(N-ethyl-N-isopropyl) amiloride (EIPA)
      sensitive Na+/H+ exchange accounted for the recovery from intracellular acidosis.
      In the presence of HCO3- ions the response to respiratory acidosis (CO2 influx)
      was predominantly via activation of Na+/H+ exchange and an EIPA sensitive Na+ and
      HCO3- dependent mechanism. A 4-acetamido-4'-isothiocyanostilbene-2',2'-sulphonic
      acids (SITS) sensitive Na+ dependent Cl-/HCO3- mechanism which is also sensitive
      to EIPA makes a small contribution during severe intracellular acidosis. Under
      such conditions HCO3- dependent mechanisms contributed about 40% to the overall
      pHi regulating capacity of vascular smooth muscle cells. However, under
      conditions which deplete cellular ATP these pHi regulating mechanisms account for
      virtually all of theses cells' ability to regulate pHi. The inability of Na+/H+
      exchange to participate in pHi recovery under these circumstances, reduces the
      ability of vascular smooth muscle cells to recover pHi by approximately 50-60%.
      Chloride efflux was approximately linear over 5 min and was increased by 36% in
      the presence of extracellular HCO3-. Efflux in the presence of HCO3- was
      inhibited similarly by both SITS and EIPA. CONCLUSIONS: At least three
      transporters contribute to recovery from acidosis in vascular smooth muscle:
      Na+/H+ exchange, an Na(+)-HCO3- cotransporter which is sensitive to EIPA, and an
      Na+ dependent HCO3-/Cl- exchange sensitive to both SITS and EIPA. The Na(+)-HCO3-
      cotransporter appears to be similar to that described in human vascular smooth
      muscle. When the Na+/H+ exchanger is attenuated by cellular ATP depletion, the
      alternative pathways, particularly the Na(+)-HCO3- cotransporter, ensure that
      substantial pHi regulatory capacity is maintained.

PMID- 7736502
TI  - Modulation of sodium-hydrogen exchange activity in cardiac myocytes during
      acidosis and realkalinisation: effects on calcium, pHi, and cell shortening.
AB  - OBJECTIVE: The aim was to examine the effects of the Na+/H+ exchange inhibitor
      methylisobutylamiloride (MIA) as well as protein kinase C, a putative regulator
      of Na+/H+ exchange, on intracellular calcium, intracellular pH, and unloaded cell
      shortening in isolated guinea pig cardiac myocytes subjected to lactic acid
      induced acidosis followed by realkalinisation. METHODS: Calcium transient
      amplitude and cell shortening were measured simultaneously in single isolated
      myocytes loaded with fura2-AM. Intracellular pH was measured in cells loaded with
      BCECF-AM. RESULTS: Exposure of cells to 5 min of lactate (20 mM) acidosis (pH
      6.8) caused an increase in calcium transient amplitude and a decrease in cell
      shortening and intracellular pH. During realkalinisation (pH 7.3), the calcium
      transient gradually decreased while intracellular pH became more alkaline than
      pre-acidosis values. The cells underwent transient hypercontractility as
      evidenced by a marked increase in systolic cell shortening and a decrease in
      diastolic cell length. Inhibition of sodium/hydrogen exchange with MIA (1 microM)
      caused a significant attenuation of the increase in calcium transient amplitude
      during acidosis and further depressed cell shortening as well as intracellular
      pH. In addition, MIA significantly attenuated hypercontractility and abolished
      cell contracture upon realkalinisation. In contrast, phorbol 12-myristate 13
      acetate (10(-12) M) exerted no effects on the response to acidosis; however, this
      treatment exacerbated cell hypercontractility and reduced functional recovery
      upon realkalinisation. CONCLUSIONS: Inhibition of Na+/H+ exchange activity during
      acidosis/realkalinisation enhances recovery of cell function.

PMID- 7736503
TI  - Role of sodium-hydrogen exchange in the proliferation of immortalised
      lymphoblasts from patients with essential hypertension and normotensive subjects.
AB  - OBJECTIVE: The aim was to investigate the effect of ethylisopropylamiloride
      (EIPA), an inhibitor of Na+/H+ exchange, and of extracellular pH on the
      proliferation of immortalised lymphoblasts derived from patients with essential
      hypertension and normotensive controls. METHODS: Na+/H+ exchange activity was
      determined in cells loaded with the fluorescent pH indicator BCECF. Cell
      proliferation was determined by FACS analysis, by cell counting, and from the
      incorporation of [3H]-thymidine. RESULTS: EIPA inhibited the Na+/H+ exchanger
      with an average KI value of 14 nM in all cell lines. Cell growth and DNA
      synthesis were only inhibited at EIPA concentrations > 10 microM suggesting a non
      specific effect independent of Na+/H+ exchanger blockade. When extracellular pH
      was varied from 7.1 to 7.7 by changing the HCO3- concentration at constant PCO2,
      cell proliferation was optimal at pH 7.4, but reduced at acidic and alkaline pH
      in cells from normotensive and hypertensive subjects. The increased proliferation
      of lymphoblasts from hypertensive subjects persisted over the whole pH range.
      Comparable results were obtained when pH was altered by varying the PCO2 at
      constant HCO3-. Preincubation of cells with pertussis toxin inhibited serum
      stimulated DNA synthesis by 14.5% and 23.5% (P = 0.02) in cell lines from
      normotensive and hypertensive subjects. CONCLUSIONS: The enhanced Na+/H+
      exchanger activity in lymphoblasts from patients with essential hypertension is
      obviously not the major determinant of the enhanced proliferation of these cells.
      The increased sensitivity of the growth of "hypersensitive" cell lines to
      pertussis toxin suggests a cellular alteration which resides upstream of Na+/H+
      exchange activity and proliferation control.

PMID- 7736504
TI  - Protective effects of HOE642, a selective sodium-hydrogen exchange subtype 1
      inhibitor, on cardiac ischaemia and reperfusion.
AB  - OBJECTIVE: The aim was to characterise the new compound HOE642 as a selective and
      cardioprotective Na+/H+ exchange inhibitor in various models. METHODS: The effect
      of HOE642 was tested in the osmotically activated Na+/H+ exchange of rabbit
      erythrocytes and in propionate induced swelling of human thrombocytes. Recovery
      of pH after an NH4Cl prepulse and effects on other ion transport systems by patch
      clamp technique were investigated in rat cardiomyocytes. NHE subtype specifity of
      the compound was determined by 22Na+ uptake inhibition in a fibroblast cell line
      separately expressing subtype isoforms 1-3. Protective effects of HOE642 in
      cardiac ischaemia and reperfusion by ligation of coronary artery were
      investigated in isolated working rat hearts and in anaesthetised rats. RESULTS:
      HOE642 concentration dependently inhibited the amiloride sensitive sodium influx
      in rabbit erythrocytes, reduced the swelling of human platelets induced by
      intracellular acidification, and delayed pH recovery in rat cardiomyocytes. In
      the isolated working rat heart subjected to ischaemia and reperfusion HOE642 dose
      dependently reduced the incidence and the duration of reperfusion arrhythmias. It
      also reduced the the release of lactate dehydrogenase and creatine kinase, and
      preserved the tissue content of glycogen, ATP, and creatine phosphate. In
      anaesthetised rats undergoing coronary artery ligation intravenous and oral
      pretreatment with HOE642 caused a dose dependent reduction or a complete
      prevention of ventricular premature beats, ventricular tachycardia, and
      ventricular fibrillation. The compound was well tolerated and neutral to
      circulatory variables. Other cardiovascular agents tested in this model were not,
      or were only partly, effective at doses showing marked cardiodepressive effects.
      CONCLUSIONS: HOE642 is a very selective NHE subtype 1 inhibitor showing
      cardioprotective and antiarrhythmic effects in ischaemic and reperfused hearts.
      Further development of well tolerated compounds like HOE642 could lead to a new
      therapeutic approach in clinical indications related to cardiac ischaemia and
      reperfusion.

PMID- 7736505
TI  - Inhibition of sodium-hydrogen exchange reduces infarct size in the isolated rat
      heart--a protective additive to ischaemic preconditioning.
AB  - OBJECTIVES: Inhibition of Na+/H+ exchange with amiloride analogues has been shown
      to protect the ischaemic and reperfused heart. The aim of this study was to
      examine if preischaemic or postischaemic treatment with the selective Na+/H+
      exchange inhibitor ethyl-isopropyl amiloride (EIPA, 1 microM) influenced infarct
      size in an isolated rat heart model of regional ischaemia and reperfusion, and if
      any such protection was additive to the protection afforded by ischaemic
      preconditioning. METHODS: Langendorff perfused rat hearts were subjected to 30 or
      45 min of regional ischaemia and 120 min of reperfusion. The risk zone was
      determined by fluorescent particles and infarct size was determined by staining
      with triphenyltetrazolium chloride. RESULTS: Treatment with EIPA for 20 min
      before 30 min regional ischaemia significantly reduced infarct size (in % of the
      risk zone) compared to untreated controls [3.1 (SEM 1.0)% v 38.1(5.8)%, P <
      0.001], a protection similar to that afforded by ischaemic preconditioning
      [6.1(2.5)%]. Combination of preischaemic EIPA treatment and ischaemic
      preconditioning also reduced infarct size [5.2(2.0)%, P < 0.01 v control group].
      When EIPA was added to the buffer only during the first 30 min of reperfusion, no
      protection was observed [infarct size = 37.8(5.8)%, NS v control group]. In order
      to clarify if the protection observed with EIPA treatment was additive to
      protection by ischaemic preconditioning, another set of experiments was
      performed. In these experiments regional ischaemia was extended to 45 min.
      Preischaemic EIPA treatment reduced infarct size also in this model compared to
      controls [15.3(2.9)% v 64.3(2.9)%, P < 0.001], as did ischaemic preconditioning
      [23.5(4.2)%, P < 0.001 v controls, NS v EIPA treated hearts]. Combination of
      ischaemic preconditioning and preischaemic EIPA treatment further reduced infarct
      size significantly [3.9(0.6)%, P < 0.05 v all other groups with 45 min regional
      ischaemia]. CONCLUSIONS: Inhibition of Na+/H+ exchange reduces infarct size in
      the isolated rat heart infarct model if the exchanger is inhibited during the
      ischaemic period, and this protection is additive to the protection afforded by
      ischaemic preconditioning.

PMID- 7736506
TI  - Stimulation of sarcolemmal sodium-hydrogen exchange in cardiac myocytes is not
      responsible for the positive inotropic action of alpha 1 adrenergic agonists.

PMID- 7736507
TI  - Stimulation of sarcolemmal sodium-hydrogen exchange in cardiac myocytes as a
      mediator of the positive inotropic action of alpha 1 adrenergic agonists.

PMID- 7736508
TI  - How high does intracellular sodium rise during acute myocardial ischaemia?

PMID- 7736509
TI  - How high does intracellular sodium rise during acute myocardial ischaemia? A view
      from NMR spectroscopy.

PMID- 7736510
TI  - Commentaries on the cardiovascular controversy on intracellular sodium in
      ischaemia.

PMID- 7736511
TI  - Commentaries on the end of year editorial on the definition of ischaemia in last
      December's issue.

PMID- 7736512
TI  - Advances in the Applications of Monoclonal Antibodies in Clinical Oncology.
      Proceedings of a meeting. Paphos, Cyprus, May 3-5, 1993.

PMID- 7736513
TI  - Linking radiosilver to monoclonal antibodies reduced by ascorbic acid. Comparison
      of results with stable silver using gravimetric technique and silver 110-M using
      radiotracer technique.
AB  - Radiosilver-111 and Radiogold-199 were proposed by us (1) as suitable isotopes
      for radioimmunotherapy in areas such as India by reason of their suitable half
      lives and B-emissions (Ag-111 T1/2 = 7.45 d and Au-199 T1/2 = 3.15 d). Since
      silver is monovalent, it is difficult to link to conventional bifunctional
      chelates. We therefore explored the use of sulfur-based linkers (2). Encouraged
      by the Thakur and De Fulvio Technique (3) of linking technetium to disulfide
      groups in antibodies reduced by ascorbic acid that is eminently biocompatible, we
      have explored the linkage of silver to immunoglobulin reduced by ascorbic acid.
      The linkage of silver was assessed with stable Ag-108 using dialysis to quantify
      the free silver after the reaction of silver and reduced immunoglobulins in
      various molar ratios (1:1, 1:2, 1:5, 1:10). The silver quantity was estimated
      gravimetrically after precipitation as chloride. It was observed that using these
      molar ratios there was negligible silver efflux into the dialysate, suggesting
      stable linkage. We also assessed the linkage using Ag-110M as radiotracer. The
      comparative results with the two techniques are described.

PMID- 7736514
TI  - Biosensor analysis of antigen-antibody interactions as a priority step in the
      generation of monoclonal bispecific antibodies.
AB  - A biosensor system aimed at real-time measuring molecular interactions among
      label-free reactants has been used for a comparative analysis of the binding
      features (i.e., association-dissociation rates and affinity constants) as well as
      epitope mapping between bivalent monoclonal antibodies and the derived monovalent
      bispecific monoclonal antibody. The results show that observed different
      affinities between parental and derived bispecific antibodies concern the
      association rate constant, whereas the dissociation rate constants are unaltered.
      The apparent affinity-constant values determined by solid-phase radioimmunoassay
      yielded figures almost overlapping with those obtained with the biosensor
      instrument. The results of the present work indicate that the biosensor system
      has gained a key role not only as a tool for the study of antigen-antibody
      interactions, but also for setting up the reference parameters for the selection
      of the best candidates in the generation of bispecific monoclonal antibodies.

PMID- 7736515
TI  - Effect of a bifunctional monoclonal antibody directed against a tumor marker and
      doxorubicin on the growth of epidermoid vulvar carcinoma grafted in athymic mice.
AB  - Even though the first monoclonal antibodies (MAbs) directed against tumor cells
      were produced 15 yr ago, the therapeutic application of immunoconjugates is still
      at the beginning. This is principally because of the enormous work that is
      required for the development of completely new therapeutic tools. An alternative
      could be to only use MAbs to improve conventional treatment such as chemotherapy.
      To this aim, a MAb directed against doxorubicin (DXR) was produced. DXR is an
      anthracycline antibiotic of which the clinical usefulness in cancer chemotherapy
      is limited by serious side effects, such as cardiomyopathy, bone marrow
      depression, and gastrointestinal tract mucositis. This toxicity was found to be
      reduced by treatment with the antidrug MAb, as shown by reduction in body weight
      loss and mortality of experimental mice. To improve the DXR therapeutic index, a
      bifunctional hybrid MAb (DOXER2), capable of simultaneously recognizing DXR and
      the epidermal growth factor (EGF) receptor, was produced. This reagent was found
      in vitro to increase the drug toxicity on the epidermoid carcinoma cell line
      A431, which overexpresses the EGF-R and, at the same time, to reduce DXR
      cytotoxicity on EGF-R negative cells. The effect of DOXER2 on the DXR
      biodistribution in vivo was also investigated. In mice previously injected ip
      with the DOXER2, the uptake of the drug, in comparison to the control group, was
      found to be reduced in the intestine and in myocardial tissue, and significantly
      increased in the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736516
TI  - Conjugates of COL-1 monoclonal antibody and beta-D-galactosidase can specifically
      kill tumor cells by generation of 5-fluorouridine from the prodrug beta-D
      galactosyl-5-fluorouridine.
AB  - 5'-O-beta-D-galactosyl-5-fluorouridine is a prodrug that can be converted by the
      enzyme beta-D-galactosidase to the potent antineoplastic drug 5-fluorouridine.
      The prodrug is more than 100x less toxic than the drug to bone marrow cells in
      Balb/c mice. The ratio of the IC50 of the prodrug to that of the drug determined
      on a variety of tumor cell lines in vitro ranged from 500:1-1000:1. An antibody
      enzyme conjugate (AEC) was synthesized and purified. Maleimide-substituted COL-1
      anti-CEA monoclonal antibody was linked to free thiol groups of beta-D
      galactosidase. The conjugate was purified by size exclusion and ion exchange
      chromatography. It retained full immunoreactivity and enzyme activity. After
      binding to antigen-positive tumor cells, the conjugate was able to activate the
      prodrug and specifically kill the cells. We are continuing to investigate this
      model for its potential use in antibody-directed enzyme prodrug therapy (ADEPT).

PMID- 7736517
TI  - Complete ablation of small squamous cell carcinoma xenografts with 186Re-labeled
      monoclonal antibody E48.
AB  - In previous studies we have shown that in mice bearing head and neck squamous
      cell carcinoma (HNSCC) xenografts, radioimmunotherapy (RIT) with 186Re-labeled
      MAb E48 resulted in complete regressions in one-third of the tumors (followup >
      150 d). MAb E48 was labeled with 186Re following a novel labeling procedure
      developed at our institute. The injected dose was 600 microCi, which was the
      maximum tolerated dose (MTD; < 15% wt loss) in these studies. The mean size of
      the tumors was 140 +/- 60 mm3. To investigate whether the therapeutic efficacy of
      RIT in our xenograft model would be improved when treating smaller xenografts,
      mice bearing 2 HNSCC xenografts with a vol of 75 +/- 17 mm3 (number of mice, n =
      6; number of tumors, t = 12) were treated with 600 microCi of 186Re-labeled MAb
      E48 IgG. All tumors completely regressed and did not regrow during followup (>
      150 d). In all mice, weight loss did not exceed 10%. To obtain biodistribution
      data, mice bearing two xenografts with a vol of 58 +/- 31 mm3 were injected with
      100 microCi of 186Re-labeled MAb E48 IgG. The maximum uptake in blood was 26.4%
      injected dose/g (%ID.g-1) at 2 h pi and was 53.1%ID.g-1 in the tumor at d 7 pi.
      In normal tissues, no nonspecific accumulation was observed. Based on these
      biodistribution data, the absorbed cumulative radiation dose was calculated. The
      accumulated dose in blood and tumor was 2004 cGy and 8580 cGy, respectively. In
      other tissues, the dose was less than 8.1% of the dose delivered to
      tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736518
TI  - Anti-idiotype and recombinant antigen in immunotherapy of colorectal cancer.
AB  - The CO17-1A/GA733 antigen (Ag), bound by monoclonal antibodies (MAb) CO17-1A and
      GA733 that define two different epitopes on the Ag, has proven a useful target in
      passive and active immunotherapy of colorectal carcinoma (CRC). Previous studies
      suggest that the antitumor effects demonstrated in MAb-treated patients may be
      mediated by idiotypic cascades. In approaches to active immunotherapy against the
      Ag, polyclonal goat and monoclonal rat anti-idiotypic antibodies (Ab2) directed
      against MAb CO17-1A or GA733 (Ab1) were administered as alum precipitates to 54
      patients with CRC (stage Dukes' B, C, and D). The majority of the patients
      treated with the various Ab2 preparations developed anti-anti-idiotypic
      antibodies (Ab3) that specifically bound to the CO17-1A or GA733 epitope and
      shared idiotopes with the corresponding Ab1. Approximately 30% of the patients
      tested developed specific cellular immunity, i.e., Ag-specific T-cells mediating
      delayed-type hypersensitivity (DTH) reaction in vivo or proliferating on
      stimulation with the Ag in vitro. The humoral and cellular immune responses may
      underlie the clinical responses observed in some of the treated patients.
      Recently, the CO17-1A/GA733 Ag has been molecularly cloned and expressed in
      baculo-, adeno-, and vaccinia viruses. In preclinical studies, these recombinant
      Ag preparations elicited specific humoral immunity (cytotoxic antibodies) and
      cellular immunity (DTH-reactive and proliferative T-cells), similar to the native
      Ag. Antibody titers elicited in experimental animals by recombinant Ag were
      significantly higher than those elicited by Ab2, presumably because Ag expresses
      numerous epitopes, whereas Ab2 mimics a single epitope. Recombinant CO17-1A/GA733
      Ag has potential as a vaccine for CRC patients.

PMID- 7736519
TI  - Potent antitumor effects of an antitumor endothelial cell immunotoxin in a murine
      vascular targeting model.
AB  - Immunotoxins and other antibody-based therapeutic reagents have proved effective
      agonist lymphomas and leukemias, but results with carcinomas and other solid
      tumors have thus far been less impressive. A major reason for this difference is
      that macromolecules penetrate poorly and unevenly into solid tumors. A solution
      to this problem would be to attack the endothelial cells of the tumor vascular
      bed rather than the tumor cells themselves. We have developed a murine model of
      this vascular targeting approach where transfection of the tumor cells with a
      cytokine gene causes them to induce the expression of an experimental marker (MHC
      Class II) on tumor endothelium. In this report we show that an anti-Class II
      deglycosylated Ricin A-chain immunotoxin kills IFN-gamma-activated endothelial
      cells in culture and, when injected into tumor-bearing Balb/c nude mice, causes
      complete thrombosis of the tumor vasculature, widespread infarction, and dramatic
      regressions of large solid tumors. These findings suggest that immunoconjugates
      prepared with recently described antibodies against human tumor endothelium could
      provide a broad-based therapy for variety of solid cancers in humans.

PMID- 7736520
TI  - Preclinical studies of monoclonal antibodies for intravesical radioimmunotherapy
      of human bladder cancer.
AB  - Eighty percent of bladder cancers present as superficial disease. Many are
      multifocal, and apparently successful treatment is frequently followed by
      recurrence. The use of monoclonal antibodies (MAbs) to target radiotherapy to
      these tumors offers great potential, especially since they can be administered
      directly into the bladder (intravesically) bypassing many of the side effects
      encountered to date with systemic MAb-based therapy. Implantation of human
      bladder cancer cell lines in the bladder wall of nude rats results in tumor
      formation, providing an excellent model to test this. Tumor size can be monitored
      by X-ray analysis after administration of urograffin. Comparative studies of two
      murine MAbs, BLCA-8, IgG3, and C1-137, IgG1, against malignant human bladder
      cancer cells have been performed. Radioimmunoconjugates produced with 125Iodine
      (125I) have been used for biodistribution studies following administration
      directly into rat bladder. Radioiodinated intact MAbs or Fabs administered
      intravesically into nontumor bearing rats did not leak into the systemic
      circulation and were stable in urine for up to 100 h. Biodistribution studies
      carried out following intravesical administration of radioimmunoconjugates to
      tumor-bearing nude rats indicate better tumor uptake of C1-137 than BLCA-8.
      Further studies to test two-step intravesical administration of biotinylated MAb
      followed by radioiodinated streptavidin are in progress. Our studies indicate
      that the C1-137 MAb may have considerable potential for intravesical
      radioimmunotherapy of patients with superficial bladder tumors.

PMID- 7736521
TI  - In vitro activity of immunoconjugates between cisplatin and an anti-CA125
      monoclonal antibody on ovarian cancer cell lines.
AB  - Cis-diammine dichloro platinum (II) (CDDP), is a highly potent antineoplastic
      agent that is used in the treatment of ovarian cancer. However, the clinical use
      of CDDP is restricted by its severe side effects. In order to reduce these side
      effects and to enhance its therapeutic efficacy, we developed specific
      immunoconjugates consisting of the murine monoclonal antibody OC125 and CDDP,
      using diethylene triamine pentaacetic acid (DTPA) as a linker. The coupling
      efficiencies of the different preparations synthesized, varied between 1.10 +/-
      0.42 and 2.65 +/- 1.60 mol of CDDP per mol of antibody protein. Despite the
      chemical modification of the antibody molecule, specific binding activity of the
      OC125-CDDP conjugates toward the CA125 antigen was maintained as was demonstrated
      by means of immunohisto-/cytochemical staining of frozen sections of ovarian
      cancer tissue, amniotic epithelium, and the CA125 positive ovarian cancer cell
      line NIH:OVCAR 3. The antiproliferative activity of the immunoconjugates was
      tested against the human ovarian cancer cell lines NIH:OVCAR 3 and SKOV 3,
      applying a kinetic crystal violet microassay. Despite the promising results
      obtained with the specific immunostaining of the target cells, no significant
      antiproliferative activity of our immunoconjugates against the cell lines tested
      was observed. One possible explanation for the lack of antitumor activity could
      be the fact that CA125 is released in large amounts by the NIH:OVCAR 3 cells.
      This may have prevented an efficient immunotargeting of the cancer cells by the
      formation of soluble immune complexes.

PMID- 7736522
TI  - Comparison of the cellular internalization of antibodies used either as
      immunotoxins or in ADEPT.
AB  - The internalization into tumor cells of two antibodies (C242 and 454A12), which
      make potent immunotoxins when linked to ricin A-chain, and an antibody (A5B7),
      which does not make a potent immunotoxin but has proven useful in ADEPT, was
      evaluated. The 454A12 antibody was rapidly taken into the cells, 50% of the
      antibody being internalized after 2 h. The C242 antibody was internalized more
      slowly, approx 50% being taken up by the cells in 24 h. With A5B7, less than 10%
      of the antibody was internalized after 24 h. Internalization of the C242 antibody
      was accompanied by the appearance of antibody degradation products in the cell
      medium after 2 h, and this degradation could be inhibited by addition of a
      metabolic inhibitor that prevented cell internalization. In contrast, minimal
      degradation of the A5B7 antibody could be detected up to 24 h after binding to
      the cells. In conclusion, both 454A12 and C242 antibodies, which make potent
      immunotoxins, were internalized into tumor cells. The A5B7 antibody, which does
      not make a potent immunotoxin, was not internalized, and this property may be one
      reason why A5B7 has proved useful for delivery of enzymes in ADEPT.

PMID- 7736523
TI  - Comparison of two anthracycline-based prodrugs for activation by a monoclonal
      antibody-beta-glucuronidase conjugate in the specific treatment of cancer.
AB  - Antibody-directed enzyme prodrug therapy (ADEPT) may improve the therapeutic
      index of cytostatic agents. We compared two prodrugs, epirubicin-glucuronide (Epi
      glu) and doxorubicin-spacer-glucuronide (Dox-sp-glu), for their cytotoxicity on
      activation by a monoclonal antibody-enzyme conjugate bound to tumor cells. The
      results showed that the prodrugs were 10 (Dox-sp-glu) and 100 (Epi-glu) times
      less toxic than the parent drugs against OVCAR-3 cells. This difference was a
      result of the hydrophilic property of the prodrugs resulting in a reduced
      cellular uptake. The enzyme-catalyzed hydrolysis of Dox-sp-glu by E. coli-derived
      beta-glucuronidase (GUS) (Km 500 microM, Vmax 21,000 mumol/min/g) was much more
      efficient than that of Epi-glu (Km 10 microM, Vmax 40 mumol/min/g). Incubation of
      OVCAR-3 cells with an enzyme-immunoconjugate prepared from monoclonal antibody
      323/A3 and E. coli-derived GUS before treatment with prodrugs completely restored
      the cytotoxicity of the prodrugs to the level of the parent drugs.

PMID- 7736524
TI  - Analysis of antibody-enzyme conjugate clearance by investigation of prodrug and
      active drug in an ADEPT clinical study.
AB  - Antibody-directed enzyme prodrug therapy (ADEPT) separates the cytotoxic function
      from the targeting function (5). An antibody-carboxypeptidase G2 (CPG2) enzyme is
      delivered prior to the nontoxic prodrug, CMDA, which is converted to a cytotoxic
      drug by the action of the localized conjugate at the tumor site. An indirect in
      vitro assay was developed to detect the presence of functional CPG2 in the plasma
      of patients in an ADEPT clinical trial. Compounds in the plasma of patients were
      characterized using liquid chromatography-mass spectrometry. Plasma at three
      different time points (prior to treatment, post-antibody-enzyme conjugate, and
      post-galactosylated anti-enzyme antibody clearing agent) was added to the CMDA
      prodrug and analyzed. Conversion of the CMDA prodrug to its active drug indicates
      that CPG2-conjugate remains in the plasma. This technique will provide essential
      data for the timing of prodrug administration in ADEPT.

PMID- 7736525
TI  - Biological studies and potential therapeutic applications of monoclonal
      antibodies and small molecules reactive with the neu/c-erbB-2 protein.
AB  - The overexpression of the growth factor receptor p185neu/c-erbB-2 has been
      observed in a number of human adenocarcinomas and is mechanistically linked to
      neoplastic growth. Monoclonal antibodies raised against extracellular domains of
      the p185neu/c-erbB-2 receptor oncoprotein have been utilized to inhibit the
      pathway of neu-induced tumor development. Our laboratory has demonstrated a
      direct effect of anti-p185neu/c-erbB-2 antibodies which requires receptor
      ligation. This induced aggregation causes the downmodulation of cell-surface
      expression and eventual degradation of p185neu/c-erbB-2 protein. In cells
      transformed by the neu oncogene, the result of antibody-induced p185neu/c-erbB-2
      receptor modulation is the reversion of the malignant phenotype. We are
      exploiting the direct efficacy of this monoclonal antibody by developing small
      molecules (peptides and organic mimietics) based on anti-p185neu/c-erbB-2
      antibody structure that can mediate similar receptor binding and biological
      effects.

PMID- 7736526
TI  - Antibody-directed enzyme prodrug therapy (ADEPT). A three-phase study in ovarian
      tumor xenografts.
AB  - Antibody-directed enzyme prodrug therapy (ADEPT) has been studied in a human
      ovarian carcinoma xenograft grown subcutaneously in nude mice. Radioimmunoassay
      of supernatants obtained from tumor homogenates showed these to contain
      carcinoembryonic antigen (CEA). Biodistribution studies with 125I-labeled
      monoclonal anti-CEA antibody, A5B7, and its F(ab')2 fragment showed localization
      in these xenografts. The AB57-F(ab')2 fragment conjugated to a bacterial enzyme,
      carboxypeptidase G2 (CPG2), and, radiolabeled with 125iodine, also localized in
      the xenografts. The radiolabeled conjugate cleared from blood faster than the
      antibody alone. The percentage of injected dose per gram in tumor at 24 h
      postinjection was about fivefold lower than antibody alone. Tumor-to-blood ratio
      at 72 h after injection of the radiolabeled conjugate was 7 and the tumor-to
      normal tissue ratios at this time point ranged from 20 (liver) to 75 (colon). A
      three-phase ADEPT antitumor study was carried out in which A5B7-F(ab')2-CPG2 was
      allowed to localize and was followed by accelerated inactivation/clearance of
      blood CPG2 by a galactosylated anti-CPG2 antibody (SB43gal). A benzoic acid
      mustard-derived prodrug was injected 24 h after the conjugate, which led to
      growth delay in this tumor compared to the control untreated group. Further
      antitumor studies in this model are in progress.

PMID- 7736527
TI  - Functional expression in mast cells of chimeric receptors with antibody
      specificity.
AB  - Chimeric genes composed of a single-chain Fv domain (scFv) of an antibody linked
      with receptor chains normally present in cells of hematopoietic origin were
      constructed. Such genes could be expressed as functional surface receptors in the
      RBL-2H3 (rat basophilic leukemia) mast cell line. The chimeric receptors
      exhibited binding properties of an antibody molecule and triggered degranulation
      of transfected mast cells on stimulation with antigen. Genetically engineered
      designer cells (e.g., T-lymphocytes, mast cells, or natural killer cells),
      equipped with built-in antibody-type recognition, can be now exploited for
      immunotherapy.

PMID- 7736528
TI  - Monoclonal antibodies and idiotypic network activation for ovarian carcinoma.
AB  - Antibodies can be processed by the B- and T-cell systems and may lead to a
      selective activation of the immune system. The network structure of the immune
      system implicates the possibility of a selective immunization by the activation
      of idiotypic cascades. In a retrospective analysis, patients with advanced
      ovarian carcinoma, who had received MAb, against the cancer-associated antigen
      CA125 for diagnostic purposes, were analyzed for the production of anti-idiotypic
      antibodies, survival rate, and immunological effects. Furthermore, we started a
      prospective and randomized study for ovarian cancer patients, using a different
      antigen, TAG72, for the induction of idiotypic cascades. Our first results on 58
      patients with advanced ovarian carcinomas showed that the induction of anti
      idiotypic-antibodies against OC125 mimicking the TAA Class III CA125 leads to a
      prolongation of the survival rate, and, in extended stages, to an induction of
      antitumoral immunity, and that the induction of idiotypic cascades is also
      possible for different antigens like TAG72. Summarizing the activation of
      idiotypic network cascades seems to be a very effective way of intervention in
      the immune system of patients with advanced stages of ovarian carcinoma. A
      prospective study of the adjuvant approach seems to be necessary.

PMID- 7736529
TI  - Deoxyribonuclease I (DNAse I). A novel approach for targeted cancer therapy.
AB  - A number of phosphodiesterases, some of which possess additional biological
      activities (e.g., antitumor, immunosuppressive, and so on), have been considered
      for use in targeted tumor therapy. We propose Deoxyribonuclease I (DNase I), a
      compact, monomeric enzyme, as a very attractive candidate for targeting to tumor
      cells. Only a small amount of enzyme targeted to a cell needs to enter the
      nucleus in order to degrade the chromosomal DNA, making a cell incapable of
      further replication. We describe preliminary data on the construction of a potent
      single-chain antibody (scFv) immunotoxin based on bovine pancreatic DNAse I. The
      use of a mammalian enzyme should be much less toxic and less immunogenic than
      current immunotoxins and may expand the current limits of immunotoxin therapy.

PMID- 7736530
TI  - Targeting phosphodiesterases as a strategy for killing tumor cells.
AB  - Ribonucleases (RNases) are being employed as alternative cytotoxic proteins to
      the conventionally used ones such as ricin and Pseudomonas exotoxin. Mammalian
      RNases are attractive enzymes because of their comparable cytotoxicity when
      suitably directed and the likelihood of lower immunogenicity compared to plant
      and bacterial toxins. Bovine seminal RNase (BSRNase) is a member of the RNase
      superfamily, but differs in many interesting ways. Unlike the rest of the family
      it is dimeric, and possesses antitumor and immunosuppressive properties. These
      features make it a choice candidate for a single-chain antibody (scFv) based
      immunotoxin. This work describes preliminary data on the construction, expression
      in Escherichia coli and characterization of a tumor-specific scFv (directed
      against human placental alkaline phosphatase)-BSRNase chimeric molecule. It is
      shown that the created molecule has RNA degrading activity and antigen-binding
      activity when refolded from bacterial inclusion bodies.

PMID- 7736531
TI  - Idiotypic cascades after injection of the monoclonal antibody OC125. A study in a
      mouse model.
AB  - In an animal model, we evaluated the possibility to induce antibodies directed
      against the tumor-associated antigen CA125 by immunization with the anti-CA125
      antibody OC125 via activation of the idiotypic network. Our results show that
      Balb/c mice, immunized by repeated administrations of F(ab')2-fragments of the
      OC125 antibody (Ab1), produced anti-idiotypic antibodies (Ab2). The binding of
      these antibodies to the OC125 could be completely inhibited by the antigen CA125,
      suggesting that the anti-idiotypic antibodies imitate the original target antigen
      of the OC125. After induction of these paratope-binding anti-idiotypic antibodies
      (Ab2 beta), a murine IgG-anti-CA125 (Ab3) response arose in the same mice. The
      induction of idiotypic cascades offers the possibility of immunization against
      tumor-associated antigens without using the original antigen and breaking
      antitumor tolerance.

PMID- 7736532
TI  - Tumor targeting in a murine tumor xenograft model with the (sFv')2 divalent form
      of anti-c-erbB-2 single-chain Fv.
AB  - This investigation has utilized novel forms of the single-chain Fv (sFv), wherein
      a cysteine-containing peptide has been fused to the sFv carboxyl terminus to
      facilitate disulfide bonding or specific cross-linking of this sFv' to make
      divalent (sFv')2. The 741F8 anti-c-erbB-2 monoclonal antibody was used as the
      basis for construction of 741F8 sFv, from which the sFv' and (sFv')2 derivatives
      were prepared. Recombinant c-erbB-2 extracellular domain (ECD) was prepared in
      CHO cells and the bivalency of 741F8 (sFv')2 demonstrated by its complex
      formation with ECD. The tumor binding properties of 125I-labeled anti-c-erbB-2
      741F8 sFv, sFv', and (sFv)2 were compared with radiolabeled antidigoxin 26-10
      sFv' and (sFv')2 controls. Following intravenous administration of radiolabeled
      species to severe combined immune-deficient (SCID) mice bearing SK-OV-3 tumors
      (which over-express c-erbB-2), blood and organ samples were obtained as a
      function of time over 24 h. Comparative analysis of biodistribution and tumor-to
      organ ratios demonstrated the 741F8 sFv, sFv', and (sFv')2 had excellent
      specificity for tumors, which improved with time after injection. This contrasted
      with nonspecific interstitial pooling in tumors observed with the 26-10 sFv,
      sFv', and (sFv')2, which decreased with time after administration. Tumor
      localization was significantly better for disulfide or peptide crosslinked 741F8
      (sFv')2 having Gly4Cys tails than for monovalent 741F8 sFv' or Fab. The superior
      properties of the 741F8 (sFv')2 in targeting SK-OV-3 tumors in SCID mice suggests
      the importance of further investigations of divalent sFv analogs for
      immunotargeting.

PMID- 7736533
TI  - Recombinant proteins L and LG. Two new tools for purification of murine antibody
      fragments.
AB  - Several bacterial cell wall proteins, like proteins A and G, with valuable
      affinity for immunoglobulins have been discovered and are currently employed in
      immunological techniques. In 1988, protein L, a bacterial cell wall protein with
      Ig-binding capacity, was isolated from the anaerobic bacterial species
      Peptostreptococcus magnus. Binding data with immunoglobulin fragments suggested
      that protein L could selectively bind the variable region of human kappa light
      chains. More recently a recombinant LG fusion protein was expressed in E. coli
      containing four repeated Ig-binding domains of protein L (fragment B1-4) and two
      IgG Fc-binding protein G domains (fragment CDC). Recombinant L and LG proteins
      were tested in the purification of murine monoclonal IgG and their fragments.
      After affinity-constant evaluation in different buffer systems, high-pressure
      affinity-chromatography columns were prepared by coupling the proteins to Affi
      prep 10 resin and tested with eight different murine monoclonal antibodies and
      their fragments of various isotypes. Affinity-chromatography experiments
      confirming radioimmunoassay results showed 75% fragment-binding capacity of
      protein L and 100% of protein LG. These results evidenced protein LG as the most
      powerful Ig-binding tool so far described. Therefore, application of these
      proteins may be suggested in the purification of murine immunoglobulins and their
      fragments, including the engineered ones.

PMID- 7736534
TI  - Preclinical models for the evaluation of targeted therapies of metastatic
      disease.
AB  - It has been estimated that approx 60-70% of cancer patients harbor overt or
      subclinical metastases at diagnosis, and it is the eradication of such systemic
      disease that largely determines survival. Preclinical tumor model systems
      employed to evaluate potential new treatment strategies should aim to represent
      the process and patterns of metastasis of their clinical counterparts as closely
      as possible. Severe combined immune-deficient (SCID) and nu/nu mice have been
      extensively used as hosts for the growth of human tumor cell lines and in some
      cases fresh tumor material. However, in most instances the resulting neoplasms
      fail to metastasize, and the aberrant immune systems of such animals has limited
      their use mainly to passive therapies of localized disease. Recently, the
      development of specially selected tumor variants and the use of appropriate
      orthotopic sites for implantation has provided several models in which
      dissemination can be demonstrated. Where the gene coding for a potential target
      antigen has been cloned, and where its overexpression or mutation is associated
      with malignancy (e.g., c-erbB-2, H-ras), transgenic mice may yield tumors that
      will develop in these immunocompetent hosts. In some cases such tumors exhibit
      metastasis. A third approach is to transfect human genes of interest into
      appropriate rodent tumors expressing the desired metastatic phenotype. These
      various approaches are compared with particular reference to mammary carcinoma
      biology.

PMID- 7736535
TI  - Study of peripheral blood lymphocyte subset distribution and IL-2 receptor (IL-2
      R) p55-p75 subunit expression in patients with cancer of different sites.
AB  - The aim of the study was to evaluate the subset distribution and the IL-2 R p55
      p75 subunit expression on unstimulated and phytohemagglutinin (PHA)-stimulated
      (at 3-d) peripheral blood mononuclear cells (PBMC), of patients with solid
      cancers of different sites. Indeed the expression of the two subunits of IL-2 R
      is an essential prerequisite for the action of the IL-2 on CD8+, CD16+
      lymphocytes as effectors in antitumor activity (LAK-cell). The subset
      distribution (CD3, CD4, CD8, CD16, DR) was assessed by cytofluorometry with
      specific monoclonal antibodies (MAbs); the p55 (CD25) and p75 subunit expression
      was evaluated by specific MAb (OKT26a and anti-p75). Ninety patients with
      advanced cancer (mainly non-small cell lung cancer [NSCLC], head and neck cancer,
      and gynecological cancer; mean age 55 yr; range 27-80) were studied. Thirty-five
      age- and sex-matched healthy subjects were studied as controls. Our data show
      that there is no significant difference in the subset distribution between cancer
      patients and controls. Furthermore, no difference has been found in the
      expression of p55 subunits on unstimulated PBMC between cancer patients and
      controls. No difference has been found in the expression of both p55 and p75
      subunits on PHA-stimulated PBMC between cancer patients and controls. Our results
      can support the rationale for further clinical trials with IL-2 in solid
      malignancies.

PMID- 7736536
TI  - Combined use of 111In-labeled pentetreotide and three-step immunoscintigraphy
      with antichromogranin A monoclonal antibody in the diagnosis of pituitary
      adenomas.
AB  - For various pituitary adenomas, it has been demonstrated that somatostatin
      receptor can be present. Pilot studies have shown that radio-indium labeled
      pentetreotide allows very good scintigraphic localization of somatostatin
      receptor-bearing cell masses. Recently, the presence of CgA in pituitary adenomas
      has also been demonstrated. MAb A11, raised against CgA, has been successfully
      used with a three-step ISG for the diagnosis of neuroendocrine tumors. Therefore
      the combined use of three-step ISG with MAb A11 and radiolabeled somatostatin can
      be useful in the diagnosis of pituitary adenomas. Twelve patients, 5 secreting
      (group A) and 7 nonsecreting (group B) pituitary adenomas, were enrolled in the
      study. All patients underwent three-step ISG, and, 2 wk later, scintigraphy with
      111In-labeled pentetreotide (Octreoscan). Three-step ISG consisted of i.v.
      injection of 1 mg of biotinylated MAb A11 (first step), followed by 10 mg of
      avidin (second step) and [99mTc]PnAO-biotin (third step). Tomographic imaging
      were acquired for three-step ISG and Octreoscan at 2 and 4 h after radiotracer
      injection, respectively. The results are the following: 2 patients of group A
      (secreting tumors) had a positive three-step ISG, whereas all the patients but
      one of the same group had a positive pentetreotide study; all the patients of
      group B (nonsecreting tumors) had a positive three-step ISG and 4 had a positive
      pentetreotide scintigraphy. These data suggest the utility of the combined use of
      these techniques for a better diagnosis of pituitary adenomas.

PMID- 7736537
TI  - Immunotoxin studies in a model of human T-cell acute lymphoblastic leukemia
      developed in severe combined immune-deficient mice.
AB  - The transplantation of the human T-cell acute lymphoblastic leukemia (T-ALL) cell
      line HSB-2 into severe combined immune-deficient (SCID) mice was found to produce
      a disseminated pattern of leukemia similar to that seen in humans. The iv
      injection of 10(7) HSB-2 cells was associated with a universally fatal leukemia.
      Histopathological examination of animals revealed the spread of leukemia
      initially from bone marrow to involve all major organs including the meninges. An
      immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7 monoclonal
      antibody (MAb) HB2 to the ribosome inactivating protein (RIP) saporin. An in
      vitro protein synthesis inhibition assay revealed specific delivery of HB2-Sap
      immunotoxin (IT) to CD7+ HSB-2 target cells with an IC50 of 4.5 pM. In an in vivo
      study, the IT was shown to significantly prolong the survival of SCID mice
      injected with HSB-2 cells compared to untreated control animals. This therapeutic
      effect was seen both with a single injection of 10 micrograms of IT given 7 d
      after the injection of HSB-2 cells, and was even more effective when IT was
      administered as three daily injections of 10 micrograms on d 7, 8, and 9. These
      results demonstrate the useful application of human leukemia xenografts in SCID
      mice and the potential therapeutic effect of an anti-CD7 IT in human T-ALL.

PMID- 7736538
TI  - Sequencing data of the antiglioma antibody MUC 2-63 and strategy for construction
      of chimeric antibodies.
AB  - The murine monoclonal antibody MUC 2-63 detects a surface antigen expressed in
      human gliomas as demonstrated by means of immunohistochemistry and Western blot.
      In addition, MUC 2-63 has been successfully used in vivo for radioimaging in nude
      mice bearing glioma xenografts and in glioma patients. The genes coding for the
      variable regions of MUC 2-63 were isolated for construction of antibody
      derivatives with reduced immunogenic effects and of reduced size. DNA and protein
      sequencing data and strategy for construction of chimeric antibodies and single
      chain Fv fragments are presented.

PMID- 7736539
TI  - Mechanisms in removal of tumor by antibody.
AB  - We report two preliminary trials of antibody treatment of B-cell lymphoma.
      Advanced lymphoma was treated with chimeric FabFc2, in which mouse Fab' gamma is
      linked to two human Fc gamma 1 fragments so as to recruit natural effectors to
      tumor targets. Terminal lymphoma was treated with bispecific antibody (BsAb)
      which recruits the ribosome-inactivating protein saporin. These different
      mechanisms led to interesting differences in patterns of tumor clearance. Eight
      patients were treated with chimeric antibody of two specificities, each at 12
      mg/kg: anti-CD37, plus either anti-CD38 or anti-CD19 according to tumor
      phenotype. On completion of the 3-wk treatment, residual plasma antibody had a
      half-life exceeding 10 d. Tumor cells in blood disappeared rapidly. However
      significant reductions in solid masses occurred in only three patients, becoming
      apparent 3-4 wk after beginning treatment and then continuing slowly. Five
      patients were treated with preformed immune complexes of saporin and F(ab'
      gamma)2 BsAb. Although doses of saporin reached 10 mg weekly, contact with the
      tumor can only have been fleeting: plasma antibody was undetectable (< 0.5
      micrograms/mL) 48 h after infusion, whereas the saporin disappeared even faster
      and was undetectable (< 4 ng/mL) at 24 h. Tumor cells disappeared from the blood
      more slowly than occurred with chimeric antibody. In contrast shrinkage of
      extravascular tumor was more rapid, and occurred in all patients, but proved less
      durable.

PMID- 7736540
TI  - Fusion protein mediated prodrug activation (FMPA) in vivo.
AB  - A two component system, consisting of a fusion protein and an appropriate
      prodrug, suited to perform selective tumor therapy in vivo, is presented. The
      fusion protein, owing to its humanized carcinoembryonic antigen (CEA)-specific
      variable region, specifically binds to CEA-expressing tumors and has an enzymatic
      activity comparable to human beta-glucuronidase. The prodrug is a nontoxic
      glucuronide-spacer-derivative of doxorubicin decomposing to doxorubicin by
      enzymatic deglucuronidation. In vivo studies in nude mice bearing human CEA
      expressing tumor xenografts revealed that 7 d after injection of 20 mg/kg fusion
      protein, a high specificity ratio (> 100:1) was obtained between tumor and
      plasma. Injection of 250 mg/kg of prodrug at d 7 resulted in tumor therapeutic
      effects superior to conventional chemotherapy without any detectable toxicity.
      These superior therapeutic effects that were observed using established human
      tumor xenografts can be explained by the approx 10-fold higher drug
      concentrations found in tumors of mice treated with fusion protein and prodrug
      than in those treated with the maximal tolerable dose of drug alone.

PMID- 7736541
TI  - Both VH and VL regions contribute to the antigenicity of anti-idiotypic antibody
      that mimics melanoma associated ganglioside GM3.
AB  - Previously we developed a murine monoclonal anti-idiotype (anti-id) antibody
      (4C10) that mimics the melanoma-associated ganglioside antigen GM3, that is, it
      carries the internal image of GM3. 4C10 was made against the human monoclonal
      antibody (HuMAb) L612, which reacts with several types of human cancer cells,
      including melanoma and breast cancer. To reduce mouse components of 4C10, the
      constant region was replaced by a human constant domain to form the murine/human
      chimeric anti-id antibody TVE-1. In the present study, we sought to determine
      which chain (VH or VL) of the anti-id is responsible for the antigenicity of GM3.
      The TVE-1 VH and VL expression vectors were simultaneously transfected with
      either the VH or VL expression vector of a murine-human chimeric IgG antidansyl
      haptenic antibody, resulting in the construction of three different combinations
      of VH and VL chimeric antibodies. These IgG molecules were produced from the
      transfectomas, and their reactivity to HuMAb L612 was tested. Neither of the IgG
      proteins that had cross-combined the VH-VL pair showed positive results,
      suggesting that both heavy and light chains are required to express the
      antigenicity. The in vivo antigenicity of this chimeric anti-id was confirmed by
      skin tests in melanoma patients receiving active specific immunotherapy.

PMID- 7736542
TI  - Immunotargeting of urothelial cell carcinoma with intravesically administered Tc
      99m labeled HMFG1 monoclonal antibody.
AB  - Ten patients with transitional cell carcinoma (TCC) of the bladder received 3-6
      mCi of HMFG1 monoclonal antibody (MAb) intravesically. The antibody was labeled
      with Tc-99m using the 2-Iminothiolane method. All patients underwent
      transurethral resection of the bladder tumor within 12-20 h following
      intravesical administration of 99m-Tc-HMFG1. The presence of the radiolabeled MAb
      in the circulation was studied by measuring the radioactivity in the serum for a
      period up to 20 h. Three of 10 patients underwent immunoscintigraphy (SPECT) 2-3
      h postadministration and cancerous areas could be easily localized. Biopsies were
      taken from the tumor sites as well as from normal bladder mucosa. Absolute uptake
      of the administered MAb expressed as percent administered dose/kg of tissue could
      be evaluated only in eight patients. Multiple specimen taken from various tumor
      sites in every patient gave a wide range of uptake values ranging from 0 to 9.29%
      adm. dose/kg, whereas normal tissue uptake values ranged from 0 to 1.63,
      respectively.

PMID- 7736543
TI  - ADEPT and related concepts.
AB  - Antibody-based therapy has attracted interest because of its potential to improve
      selectivity. But the limitations of antibodies as delivery systems are well known
      and the objective of restricting action to tumor sites requires additional means.
      The ADEPT concept introduced two components, enzyme and prodrug, that have the
      advantage that they can be secondarily manipulated to augment the selectivity of
      the primary delivery systems. An antibody-enzyme conjugate (AEC) is no more
      selective as a delivery system than antibody itself and total catalytic capacity
      in tumor, plasma, and nontumor tissues is a function not only of concentration
      but also of volume. It is pointless giving a prodrug that is promptly activated
      by enzyme in blood. The ability to inactivate or clear plasma enzyme (PENCIL) by
      an antibody directed at its active site and modified to have low potential to
      penetrate the tumor is one of several ways of improving partition of enzyme
      between tumor and nontumor. A second opportunity for manipulation arises from
      structural differences between prodrug and active drug and the potential of
      enzymes to exploit that difference. However effective the enzyme delivery system,
      some leakage of active drug into plasma is likely and active drug access to
      hemopoietic tissues is dose limiting. An enzyme for which the active drug, but
      not the prodrug, is substrate, and which is conjugated to a macromolecule, is
      proposed. Some thymidylate synthetase inhibitors suggest themselves as ready
      agents for use in this intravascular inactivation of active drug (IVIAD). This
      approach is an alternative to inactivation of plasma enzyme. AECs may also be
      used advantageously in the context of antimetabolites used with rescue
      agents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736544
TI  - Removal of endotoxin from antibody preparations for clinical use. Assessment of
      polymyxin-sepharose CNBr affinity chromatography.
AB  - Despite attempts to maintain asepsis, good manufacturing practices, and the use
      of terminal sterilization by millipore filtration, the nuclear practitioner is
      always worried about the possibility of endotoxin contamination. Methods, such as
      ion-exchange chromatography, have been tried for removing endotoxins during the
      preparation of radiolabeled antibodies, and so on. As suggested by Stevenson
      (1990), we evaluated the Issekutz technique (1) of endotoxin removal by affinity
      chromatography using a polymyxin cyanogen bromide (CNBr) Sepharose column. The
      endotoxin content of millipore filtrates of heat killed/sonicated suspensions of
      Pseudomonas pyocyaneus, E. coli were measured using a Sigma (St. Louis, MO)
      Endotoxin Assay Kit before and after filtration through such columns and compared
      with the results obtained using gel exclusion and ion-exchange columns of the
      same length and diameter. Reduction of endotoxin content to undetectable levels
      by the polymyxin column was observed. The use of such columns for terminal
      endotoxin removal analogous to terminal sterilization is advocated especially
      when developing a radiopharmaceutical such as radiolabeled antibodies for in
      house use.

PMID- 7736545
TI  - Clinical radioimmunolocalization with a rat monoclonal antibody directed against
      c-erbB-2.
AB  - Lymph node status is still the single most important prognostic factor in breast
      cancer and surgery remains the only reliable means of providing this information.
      This study evaluates using a highly specific radiolabeled monoclonal antibody to
      provide equivalent information. The optimum labeling conditions for radiolabeling
      a monoclonal antibody against the gene product of the protooncogene c-erbB-2 with
      Tc99m were established. This immunoconjugate was next evaluated in a mouse model
      system and averaged 20% localization of the total injected dose per gram of tumor
      at 24 h. Ten patients have had this immunoconjugate, with planar and tomographic
      reconstructed images being obtained at 24 h. The resulting images were compared
      to histopathological examination of the surgical specimens. Three patients acted
      as normal controls, two patients were selected on the basis of inappropriate
      sampling of adjacent ductal carcinoma in situ, three patients demonstrated only
      moderate antigen expression, and two patients demonstrated excellent tumor
      localization in both breast primary and regional node metastases. The high
      specificity of this antibody, ease of labeling, and excellent localization
      performance with a good antigen target encourage the development of this system
      as a method of localization and a potential means of antibody-guided therapy.

PMID- 7736546
TI  - Use of technetium antigranulocyte monoclonal antibody Fab' fragments for the
      detection of osteomyelitis.
AB  - Accurate early diagnosis of osteomyelitis is critical for optimal clinical
      management. Conventional radiology (X-rays, CT) and nuclear medicine scans (bone,
      gallium, and technetium/indium white blood cell [WBC]) have limitations and
      drawbacks. The monoclonal antibody (MAb) ImmuRAID-MN3 (Immunomedics Inc., Morris
      Plains, NJ), a 99m-Tc Antigranulocyte Fab' fragment, recognizes a surface
      glycoprotein NCA-90/95 shared by granulocytes, carcino-embryonic antigen (CEA),
      and meconium antigen (MA). Intravenous injection of radiolabeled MAb enables in
      vivo labeling of human granulocytes and targets infected lesions in the bone and
      throughout the body. Technetium labeled Fab' fragments rapidly clear the blood
      pool and high-quality images can be obtained the same day, as early as 1 h
      postinjection. Results at our institution on 13 patients with clinically
      suspected osteomyelitis of infected long bones, prostheses, and diabetic foot
      ulcers were compared with the surgical/bacteriological verification of the
      presence or absence of infection. The MAb scan showed six true positives, six
      true negatives, and one false negative (very low grade infection). The procedure
      was safe, no clinical or laboratory adverse reactions were encountered. The MAb
      fragments are markedly less immunogenic than whole IgG, resulting in lower
      induction of human antimouse antibody (HAMA) titers. No HAMA to this MAb fragment
      has been detected in 24 patients (data from multiple institutions). Our
      preliminary results suggest that 99m-Tc ImmuRAID-MN3 is highly accurate for
      detection of osteomyelitis. This study is part of an ongoing multiinstitutional
      project sponsored by Immunomedics, Inc. to evaluate the efficacy and safety of
      this radiopharmaceutical.

PMID- 7736547
TI  - Immunogold labelling of estradiol receptor in MCF7 cells.
AB  - The distribution of estradiol receptor in serial sections of estradiol-deprived
      and estradiol-stimulated MCF7 cells was studied by using mouse monoclonal
      antibodies reacting with different domains of the receptor and goat-antimouse
      IgG/6 nm gold. In the nucleus and the cytoplasm of estradiol-deprived cells, the
      receptor was detected by all three monoclonals (13H2, HT 65 and MA1-310). The
      antibodies 13H2 and MA1-310 detected receptor associated to the microfilament
      bundles in the cytoplasm. Higher densities of antireceptor attachment to the
      nuclear areas were accompanied by a reduction in the attachment to the cytoplasm
      after estradiol stimulation of the cells. The results confirm earlier
      observations on the presence of cytoplasmic estrogen receptor in estradiol
      deprived cells and support the premise of an estradiol-induced translocation of
      this ligand-dependent transcription regulator.

PMID- 7736548
TI  - Immunocytochemical colocalization of adhesive proteins with clathrin in human
      blood platelets: further evidence for coated vesicle-mediated transport of von
      Willebrand factor, fibrinogen and fibronectin.
AB  - Coated membranes and vesicles play an important role in receptor-mediated
      endocytosis and intracellular trafficking in various cell types, and are also
      present in blood platelets. Platelets take up certain proteins from the blood
      plasma, such as von Willebrand factor and fibrinogen, and these substances are
      transferred to storage granules. The receptors for these plasma proteins on the
      platelet plasma membrane have been well characterized, but morphological evidence
      for their transport to the storage granules is not yet available. In an attempt
      to clarify this aspect, we employed postembedding immunocytochemistry on
      platelets embedded in the acrylic resin LR White. Clathrin as the major coat
      component of coated vesicles was localized in the cytoplasm, on the plasmic faces
      of alpha-granules and the open canalicular system, and on the plasmic face of the
      plasma membrane. Colocalizations of the adhesive proteins, von Willebrand factor,
      fibrinogen and fibronectin, with clathrin could be observed at the same typical
      locations as coated vesicles were seen in Araldite-embedded material. These
      colocalizations have not been reported to date and furnish further evidence for a
      coated vesicle-mediated transport of blood plasma-derived adhesive proteins from
      their receptors on the outer plasma membrane to the alpha-granules.

PMID- 7736549
TI  - Sexual differences in the Golgi apparatus of rat hepatocytes: three-dimensional
      analysis.
AB  - Lipid metabolism takes place in the Golgi apparatus, but at a higher rate in
      female than in male rats. I therefore examined the Golgi apparatus by
      morphometric means for differences between the sexes at the light- and electron
      microscopic level. The Golgi apparatus was stained in situ by a zinc-iodide
      osmium method. The counts of the Golgi apparatus in cross-sections in female
      hepatocytes by light microscopy were approximately twice that in male
      hepatocytes. Upon ovariectomy, these counts were greatly reduced but were
      reestablished after estrogen supplement. To clarify this phenomenon, three
      dimensional reconstructions of the Golgi apparatus were produced from electron
      microscopic images of serially cut 160-nm sections. The Golgi apparatus of both
      male and ovariectomized females had the shape of a small ring, whereas it took
      the form of a large elongated cylinder in normal females and in castrated males
      after treatment with estrogen. The numerical difference in Golgi apparatus counts
      by light microscopy of in males and females is, therefore, apparently
      attributable to the size and shape of the Golgi apparatus, and is controlled by
      the estrogen level.

PMID- 7736550
TI  - Ultrastructural characterization of the sexually dimorphic medial preoptic
      nucleus of male Japanese quail.
AB  - The medial preoptic nucleus is a sexually dimorphic structure whose
      cytoarchitecture, afferent and efferent connections, and functions have been
      previously described. No detailed ultrastructural study has, however, been
      performed to date. Here we describe the ultrastructural organization of this
      important preoptic structure of the male quail. Neuronal cell bodies of the
      medial preoptic nucleus generally show extensive development of protein-synthesis
      related organelles (rough endoplasmic reticulum, polysomes), and of secretory
      structures (Golgi complexes, secretory vesicles, dense bodies). Previous
      morphometrical studies at the light-microscopical level have demonstrated the
      presence of a medial and a lateral neuronal population distinguished by the size
      of their cell bodies (the medial neurons are smaller than the lateral neurons).
      The present ultrastructural investigation confirms the difference in size, but no
      difference has been observed in the ultrastructural organization of the neurons.
      In both the medial and the lateral part, the nucleus is characterized by a large
      variety of cell bodies, including some that, on the basis of their
      ultrastructure, can be considered as putative peptidergic neurons. Close contacts
      are frequently observed between adjacent cell bodies that are normally arranged
      in clusters. Various types of synaptic endings are also present, suggesting a
      rich supply of nerve fibers. A few glial cells are scattered within the nucleus.
      In view of the crucial role of this region in regulating quail sexual behavior,
      the large heterogeneity of neurons and of afferent nervous fibers suggest that
      this region might have an important role in the integration of information
      arriving from different brain regions.

PMID- 7736551
TI  - The distinct gene expression of the pro-hormone convertases in the rat heart
      suggests potential substrates.
AB  - The present study examined the distribution of the pro-hormone convertases PC1,
      PC2, furin, PACE4 and PC5 in the rat heart. Northern blot analysis of RNA
      extracted from cardiac tissues showed high levels of furin and PACE4 mRNA in the
      atria and ventricles, while PC5 mRNA was found to be expressed at high levels in
      the dorsal aorta. Although undetectable by Northern blot analysis, both PC1 and
      PC2 mRNA were detected by in situ hybridization and immunohistochemistry in
      discrete regions of the intracardiac para-aortic ganglia. In situ hybridization
      studies also showed that furin mRNA was observed in all cardiac tissues and
      cells, consistent with the previously reported ubiquitous expression of this
      gene. PACE4 mRNA was highly abundant in both the atria and ventricular
      cardiomyocytes, with low to undetectable levels observed in blood vessels.
      Finally, PC5 transcripts were expressed in the endothelial cells lining coronary
      vessels and the valve leaflets of the heart. The present localization studies in
      the heart and cardiac blood vessels suggests potential roles for each convertase
      in the processing of various neuropeptides, hormones and growth factors.

PMID- 7736552
TI  - Changes in glycan distribution within the porcine interhaemal barrier during
      gestation.
AB  - Changing patterns of glycan distribution are described in porcine placentae at
      15, 19, 26, 43, 58, 69 and 109 days gestation, using a carefully selected panel
      of lectins that allowed partial analysis of saccharide classes and sequences. The
      lectins used were from Galanthus nivalis, Pisum sativum, Phaseolus vulgaris
      (leukohaemagglutinin), Triticum vulgaris, Tetragonolobus purpureus, Ulex
      europaeus-1, Arachis hypogaea, Erythrina cristagalli, Glycine max, Maclura
      pomifera, Wisteria floribunda, Dolichos biflorus, Maackia amurensis, Sambucus
      nigra and Limax flavus. During the course of gestation the trophoblast developed
      from a smooth to a deeply folded membrane, while enlarging fetal and maternal
      capillaries grew closer to each other. The fetomaternal interface expressed many
      classes of saccharide, both O- and N-linked, but failed to bind DBA, MAA and SNA.
      Many granules were present in the maternal epithelium, and a striking feature was
      the appearance of staining with DBA and UEA-1 by day 43. This stage of pregnancy
      was also associated with changes in trophoblast glycan expression, with a
      diminution in staining intensity of AHA, MPA and LTA, but an increased intensity
      with ECA, SBA and WFA. Changes in lectin binding throughout gestation are
      correlated with previous ultrastructural findings and their relevance to the
      immunological and functional aspects of pregnancy is discussed.

PMID- 7736553
TI  - Calcium concretions in the pineal gland of aged rats: an ultrastructural and
      microanalytical study of their biogenesis.
AB  - The genesis of calcium concretions in aged rats was studied by means of
      transmission and scanning electron microscopy. The potassium pyroantimonate
      method, combined with X-ray microanalysis, allowed us to study the distribution
      of cations and calcium. Notable accumulations of calcium (associated with
      phosphorus) were localized in vesicles, vacuoles, lipid droplets, lipopigments,
      and mitochondria of dark pinealocytes. The results obtained in the present
      investigation suggest that these organelles are involved in the genesis of the
      concretions. The presence of sulfur indicates the existence of an organic matrix.
      We propose that genesis takes place in dark pinealocytes, which contain more
      calcium than light pinealocytes. Mineralization foci are sometimes associated
      with cellular debris and enlarge by further apposition of material. Two types of
      concretions, as determined by electron microscopy and confirmed by electron
      diffraction, could be observed: the "amorphous" type with concentric layers and
      the crystalline type with needle-shaped crystals. Once formed, the concretions
      reach the extracellular space and the cell breaks down. Possible extracellular
      calcification is suggested in the extracellular calcium-rich floculent material.
      The mineralization process is interpreted as being an age-related phenomenon and
      mainly a consequence of the degeneration of pinealocytes.

PMID- 7736554
TI  - Morphometric analysis of atrial natriuretic peptide-containing granules in
      atriocytes of rats with experimental congestive heart failure.
AB  - The morphometric characteristics of atrial natriuretic peptide-containing
      granules were studied in atrial myoendocrine cells of rats with aorto-caval
      fistula, an experimental model of congestive heart failure. A total of 6680
      granules of control and aorto-caval rats were analyzed by a computerized image
      analysis system that evaluated the number and sectioned surface area of granules
      and their subcellular location. Compared with control animals, rats with
      congestive heart failure displayed a slight increase in the number of peripheral
      granules, adjacent to the sarcolemma, but not centrally located in the Golgi
      areas. The mean sectioned surface area of granules in rats with congestive heart
      failure was about 50% of that in controls, both in the right and left atria. Rats
      with aorto-caval fistula had a higher percent of small granules and lower percent
      of large granules compared with controls. The data demonstrate different
      morphometric characteristics in atrial natriuretic peptide-containing granules in
      atriocytes in rats with experimental congestive heart failure; this may reflect
      the enhanced synthesis and release of atrial natriuretic peptide in heart
      failure.

PMID- 7736555
TI  - Secretory granule formation and membrane recycling by the trans-Golgi network in
      adipokinetic cells of Locusta migratoria in relation to flight and rest.
AB  - The influence of flight activity on the formation of secretory granules and the
      concomitant membrane recycling by the trans-Golgi network in the peptidergic
      neurosecretory adipokinetic cells of Locusta migratoria was investigated by means
      of ultrastructural morphometric methods. The patterns of labelling of the trans
      Golgi network by the exogenous adsorptive endocytotic tracer wheat-germ
      agglutinin-conjugated horse-radish peroxidase and by the endogenous marker enzyme
      acid phosphatase were used as parameters and were measured by an automatic image
      analysis system. The results show that endocytosed fragments of plasma membrane
      with bound peroxidase label were transported to the trans-Golgi network and used
      to build new secretory granules. The amounts of peroxidase and especially of acid
      phosphatase within the trans-Golgi network showed a strong tendency to be smaller
      in flight-stimulated cells than in non-stimulated cells. The amounts of acid
      phosphatase in the immature secretory granules originating from the trans-Golgi
      network were significantly smaller in stimulated cells. The number of immature
      secretory granules positive for acid phosphatase tended to be higher in
      stimulated cells. Thus, flight stimulation of adipokinetic cells for 1 h
      influences the functioning of the trans-Golgi network; this most probably results
      in a slight enhancement of the production of secretory granules by the trans
      Golgi network.

PMID- 7736556
TI  - Immunological evidence for an allatostatin-like neuropeptide in the central
      nervous system of Schistocerca gregaria, Locusta migratoria and Neobellieria
      bullata.
AB  - Methanolic brain extracts of Locusta migratoria inhibit in vitro juvenile hormone
      biosynthesis in both the locust L. migratoria and the cockroach Diploptera
      punctata. A polyclonal antibody against allatostatin-5 (AST-5) (dipstatin-2) of
      this cockroach was used to immunolocalize allatostatin-5-like peptides in the
      central nervous system of the locusts Schistocerca gregaria and L. migratoria and
      of the fleshfly Neobellieria bullata. In both locust species, immunoreactivity
      was found in many cells and axons of the brain-retrocerebral complex, the
      thoracic and the abdominal ganglia. Strongly immunoreactive cells were stained in
      the pars lateralis of the brain with axons (NCC II and NCA I) extending to and
      arborizing in the corpus cardiacum and the corpora allata. Although many
      neurosecretory cells of the pars intercerebralis project into the corpus
      cardiacum, only 12 of them were immunoreactive and the nervi corporis cardiaci I
      (NCC I) and fibers in the nervi corporis allati II (NCA II) connecting the
      corpora allata to the suboesophageal ganglion remained unstained. S. gregaria and
      L. migratoria seem to have an allatostatin-like neuropeptide present in axons of
      the NCC II and the NCA I leading to the corpus cardiacum and the corpora allata.
      All these data suggest that in locusts allatostatin-like neuropeptides might be
      involved in controlling the production of juvenile hormone by the corpora allata
      and, perhaps, some aspects of the functioning of the corpus cardiacum as well.
      However, when tested in a L. migratoria in-vitro juvenile hormone-biosynthesis
      assay, allatostatin-5 did not yield an inhibitory or stimulatory effect. There is
      abundant AST-5 immunoreactivity in cell bodies of the fleshfly N. bullata, but
      none in the CA-CC complexes. Apparently, factors that are immunologically related
      to AST-5 do occur in locusts and fleshflies but, the active portion of the
      peptide required to inhibit JH biosynthesis in locusts is probably different from
      that of AST-5.

PMID- 7736557
TI  - Comparison of melatonin-binding sites in the brain of two amphibians: an
      autoradiographic study.
AB  - Neuroanatomic comparison of the binding capability of 2-[125I] iodomelatonin in
      the crested newt Triturus carnifex Laur. and the green frog Rana esculenta, using
      quantitative autoradiographic techniques, revealed a heterogeneous distribution
      pattern. The highest and relatively high binding activities were shown to occur
      in the optic tracts and in the suprachiasmatic area of the hypothalamus and the
      optic tectum, respectively, of both species. Low or no 2-[125I] iodomelatonin
      binding values were obtained in the preoptic nucleus, the tuberal hypothalamus,
      the medulla oblongata, the septum and the dorsal pallium. A differential binding
      pattern was observed in the amygdaloid nucleus pars lateralis, the striatum and
      the hindbrain of these amphibians. Indeed, notably high binding levels were shown
      to occur in the former two brain areas of the crested newt, whereas high levels
      were displayed in the latter brain region of the green frog. On the basis of
      elevated quantities of melatonin receptors in mesencephalic, hypothalamic and
      telencephalic sites, it seems plausible to ascribe some important sensory
      functions to this receptor system in both species. The remarkably different
      binding activities in the brain of the two amphibians could be correlated with
      the simpler cytoarchitectonic brain structure of urodeles and with species
      specific variations.

PMID- 7736558
TI  - Noradrenergic and adrenergic systems in the brain of the urodele amphibian,
      Pleurodeles waltlii, as revealed by immunohistochemical methods.
AB  - The distribution of noradrenaline and adrenaline in the brain of the urodele
      amphibian Pleurodeles waltlii has been studied with antibodies raised against
      noradrenaline and the enzymes dopamine-beta-hydroxylase and phenylethanolamine-N
      methyltransferase. Noradrenaline-containing cell bodies were found in the
      anterior preoptic area, the hypothalamic nucleus of the periventricular organ,
      the locus coeruleus and in the solitary tract/area postrema complex at the level
      of the obex. Noradrenergic fibers are widely distributed throughout the brain
      innervating particularly the ventrolateral forebrain, the medial amygdala, the
      lateral part of the posterior tubercle, the parabrachial region and the
      ventrolateral rhombencephalic tegmentum. Putative adrenergic cell bodies were
      found immediately rostral to the obex, ventral to the solitary tract. Whereas the
      cell bodies and their dendrites were Golgi-like stained, axons were more
      difficult to trace. Nevertheless, some weakly immunoreactive fibers could be
      traced to the basal forebrain. A comparison of these results with data previously
      obtained in anurans reveals not only several general features, but also some
      remarkable species differences.

PMID- 7736559
TI  - Retinal ellipsosomes: morphology, development, identification, and comparison
      with oil droplets.
AB  - We report some unique features of retinal cone ellipsosomes in mountain-stream
      teleosts. They have also been compared with oil droplets occurring predominantly
      in many reptilian and avian retinas. Ontogenetically, ellipsosome differentiation
      from ellipsoidal mitochondria occurs with advanced eye growth (diameter > 1 mm).
      In juvenile loaches, they arise almost simultaneously in the dorsal and ventral
      retina, whereas in cyprinids, they appear first dorsally in bottom-dwelling early
      juveniles (approximate age 3-4 months), and then in the ventral retina in
      migratory late juveniles (eye diameter > 4 mm, approximate age 2 years). The
      significance of the pattern of ontogeny of ellipsosomes in these stream fishes is
      discussed in relation to their utilization of a complex habitat during life. All
      adult cones possess conspicuous ellipsosomes. Histochemically, they react
      strongly with phosphotungstic-acid hematoxylin, a dye specific for proteins,
      whereas oil droplets refuse to do so (studied in turtle and pigeon). This
      reflects a major chemical difference between the two types of globules. Since
      ellipsosomes are present in the double cone accessory unit (which in higher
      vertebrates lacks an oil droplet) and since they appear late ontogenetically
      during advanced eye growth, they cannot be related to oil droplets, which have an
      embryonic developmental program.

PMID- 7736560
TI  - Review: Ca(2+)-mobilizing receptors for ATP and UTP.
AB  - Extracellular nucleotides are potent Ca2+ mobilizing agents. A variety of
      receptors for extracellular ATP are recognised. Some are involved in fast
      neuronal transmission and operate as ligand-gated ion channels. Others are
      involved in the paracrine or autocrine modulation of cell function. Many
      receptors of this type are coupled to phosphoinositide-specific phospholipase C
      and, in some cases, other phospholipases. One of these receptors (P2z), however,
      also appears to operate, at least in part, as a ligand-gated ion channel.
      Pharmacological data suggest that one nucleotide receptor subtype (currently
      designated P2U) responds selectively to either a purine nucleotide, ATP, or a
      pyrimidine nucleotide, UTP. According to an alternative view, ATP and UTP
      recognise distinct receptors. Because of the diversity of receptors for
      extracellular nucleotides this may be the case in some cells. Nevertheless, a G
      protein coupled receptor that confers both ATP and UTP sensitivity has been
      cloned, expressed in cultured cell lines and sequenced. This receptor appears to
      have two ligand binding domains that may partially overlap. The nature of this
      overlap is discussed and a simple model presented. Activation of the receptor
      protein via one or other ligand binding domain may underlie some of the more
      subtle differences between the effects of ATP and UTP.

PMID- 7736561
TI  - Serotonin elevates intracellular Ca2+ in rat choroid plexus epithelial cells by
      acting on 5-HT2C receptors.
AB  - The effects of serotonin (5-HT) on intracellular calcium activity ([Ca2+]i) in
      epithelial cells from rat choroid plexuses were examined. Experiments were
      performed on isolated cells which had been maintained in primary culture.
      ([Ca2+]i) was measured using micro-spectrofluorimetric techniques and the
      fluorescent indicator Fura-2. 5-HT was found to increase [Ca2+]i in a dose
      dependent manner. The [Ca2+]i response was biphasic, with an initial peak of
      [Ca2+]i (due to release from intracellular stores), followed by an elevated
      plateau phase (the result of calcium influx). The effect of 1 microM 5-HT was
      inhibited by mesulergine and mianserin (50 nM), which are antagonists of the 5
      HT2C receptor. Spiperone and ketanserin (200 nM), less specific 5-HT2 receptor
      blockers, caused only a slight reduction in the response to 1 microM 5-HT. The
      [Ca2+]i response decreased upon repeated challenges with 1 microM 5-HT, probably
      as a result of receptor desensitisation. Taken together, the data suggest that 5
      HT acts at 5-HT2C receptors to increase [Ca2+]i in choroid plexus epithelial
      cells, both by liberating Ca2+ from intracellular stores and by activating a Ca2+
      influx pathway.

PMID- 7736562
TI  - Effect of phorbol ester on phosphoinositide hydrolysis and calcium mobilization
      induced by endothelin-1 in cultured canine tracheal smooth muscle cells.
AB  - Regulation of the increase in inositol 1,4,5-trisphosphate (IP3) production and
      intracellular Ca2+ concentration ([Ca2+]i) by protein kinase C (PKC) was
      investigated in cultured canine tracheal smooth muscle cells (TSMCs). Stimulation
      of TSMCs by endothelin-1 (ET-1) led to IP3 formation and caused an initial
      transient peak followed by a sustained elevation of [Ca2+]i in a concentration
      dependent manner. Pretreatment of TSMCs with phorbol 12-myristate 13-acetate
      (PMA, 1 microM) for 30 min blocked the ET-1-induced IP3 formation and Ca2+
      mobilization. However, this inhibition was reduced after incubating the cells for
      8 h with PMA. Following preincubation, ET-1-induced Ca2+ mobilization recovered
      with time and reached the same extent of control cells within 48 h. The
      concentrations of PMA that gave half-maximal inhibition (-logEC50) of ET-1
      induced IP3 formation and increase in [Ca2+]i were 8.6 and 8.4 M, respectively.
      Prior treatment of TSMCs with staurosporine (1 microM), a PKC inhibitor,
      inhibited the ability of PMA to attenuate ET-1-induced responses, suggesting that
      the inhibitory effect of PMA is mediated through the activation of PKC. In
      parallel with the effect of PMA on the ET-1-induced IP3 formation and Ca2+
      mobilization, a change of PKC activity was observed in TSMCs. PMA rapidly
      decreased PKC activity in the cytosol of TSMCs, while increasing it transiently
      in the membranes within 30 min. Thereafter the membrane-associated PKC activity
      decreased and persisted for at least 24 h of PMA treatment. Taken together, these
      results suggest that activation of PKC may inhibit the phosphoinositide
      hydrolysis and consequently attenuate the [Ca2+]i increase or inhibit
      independently both responses. The PMA-induced inhibition of responses to ET-1 was
      associated with an increase in membranous PKC activity.

PMID- 7736563
TI  - IP3 receptor purified from liver plasma membrane is an (1,4,5)IP3 activated and
      (1,3,4,5)IP4 inhibited calcium permeable ion channel.
AB  - The IP3 receptor is involved in Ca2+ mobilization from intracellular stores.
      Recently, we purified an inositol (1,4,5)-trisphosphate receptor from rat liver
      plasma membrane (LPM-IP3R) [Schafer R. Hell K. Fleischer S. (1993) Purification
      of an IP3 receptor from liver plasma membrane. Biophys. J. 66, A146]. The
      purified LPM-IP3 receptor was incorporated into vesicle derived planar bilayers
      and its channel properties characterized. The receptor displayed ion channel
      activity that was activated by inositol (1,4,5)-trisphosphate [(1,4,5)IP3] (1
      microM) and inhibited by inositol (1,3,4,5)-tetrakisphosphate (IC50 approximately
      1 microM) and by heparin (IC50 approximately 20 micrograms/ml). The channel
      displays a unitary conductance of 9 pS, and 13 pS in symmetrical 100 mM and 500
      mM KCl, respectively, and in symmetrical 250 mM cesium methanesulfonate the slope
      conductance is 11 pS. Activation by (1,4,5)IP3 is specific to the cis-side of the
      chamber, equivalent to the cytoplasmic face. The receptor is a Ca2+ permeable ion
      channel based on ion selectivity (Ca2+ > K+ > Na+ >> Cl). The LPM-IP3 receptor
      was also permeable to Cs (Cs+ > or = K+), similar to other intracellular Ca2+
      release channels, i.e. the IP3 receptor from brain and smooth muscle (IP3R-1) and
      the ryanodine receptor from skeletal muscle (RyR-1) and heart (RyR-2). Channel
      activity is not voltage dependent (+/- 100 mV applied voltage). The channel is
      activated by ATP and Ca2+. The open probability of the (1,4,5)IP3 activated
      channel activity displays a bell shaped response to cis Ca2+ ion concentration of
      our system. The LPM-IP3 receptor differs from intracellular IP3R-1 in that the
      Ca2+ and ATP concentration required for maximum activation is about 10 times
      higher as compared with IP3R-1 from brain cerebellum and smooth muscle. We
      conclude that the LPM-IP3 receptor is an (1,4,5)IP3 activated Ca2+ permeable ion
      channel. The implication of our studies is that in liver, (1,4,5)IP3 regulates
      Ca2+ influx via the plasma membrane.

PMID- 7736564
TI  - Thapsigargin induces cytoplasmic free Ca2+ oscillations in mouse oocytes.
AB  - The mechanisms of calcium signalling in mammalian oocytes during maturation and
      fertilization are controversial. In this study we measured intracellular free
      Ca2+ concentrations ([Ca2+]i) with the photoprotein aequorin microinjected into
      immature mouse oocytes. Immature mouse oocytes typically produced [Ca2+]i
      responses to muscarinic acetylcholine (ACh) stimulation with two types of
      component. The first component consisted of a broad transient rise in [Ca2+]i
      lasting about 1 min. The second component consisted of pulsatile oscillations
      which could occur before, during or after the broad transient, but typically
      occurred on the rising phase of the broad transient, with a duration of about 5
      s. Removal of external Ca2+ ([Ca2+]o) abolished the Ca2+ responses to ACh.
      Exposure of oocytes to the specific microsomal Ca(2+)-ATPase inhibitors
      thapsigargin (TG) and cyclopiazonic acid unexpectedly produced sustained
      oscillations in [Ca2+]i which were sensitive to the concentration of Ca2+ in the
      external milieu. The frequency of these oscillations was slow, and ceased,
      sometimes after several cycles, when Ca2+o was removed. Raised [Ca2+]o
      significantly increased the frequency in cells oscillating to TG and stimulated
      nonoscillating cells to begin oscillating. The majority of responsive oocytes
      which did not produce oscillations to ACh alone (70%), did so after TG treatment.
      Detailed data analysis indicated that these oscillations were identical to those
      generated by TG alone, with a similar sensitivity to changes in [Ca2+]o. Exposure
      of oocytes to ryanodine did not inhibit oscillatory behaviour. These results
      suggest that immature mouse oocytes possess a store which is insensitive to both
      TG and ryanodine and is capable of supporting [Ca2+]i oscillations.

PMID- 7736565
TI  - Differences in uptake, storage and release properties between inositol
      trisphosphate-sensitive and -insensitive Ca2+ stores in permeabilized pancreatic
      acinar cells.
AB  - Rabbit pancreatic acinar cells, permeabilized by saponin treatment, were used to
      study the kinetics of ATP-dependent Ca2+ uptake and release in inositol 1,4,5
      trisphosphate (Ins-1,4,5-P3)-sensitive and -insensitive stores. Permeabilized
      acinar cells rapidly accumulated Ca2+ to steady-state. At steady state,
      approximately 60% of actively stored Ca2+ resided in the Ins-1,4,5-P3-sensitive
      store. Kinetic analysis of the Ca2+ uptake process revealed that the initial Ca2+
      uptake rate was 1.7 times higher in the Ins-1,4,5-P3-insensitive store as
      compared to the Ins-1,4,5-P3-sensitive store. On the other hand, the Ca2+ uptake
      capacity was 1.6 times higher in the Ins-1,4,5-P3-sensitive store as compared to
      the Ins-1,4,5-P3-insensitive store. The Ca2+ uptake rate in the Ins-1,4,5-P3
      sensitive store remained virtually constant for at least 4 min, whereas in the
      Ins-1,4,5-P3-insensitive Ca2+ store this rate progressively declined with time.
      These observations are compatible with: (i) an Ins-1,4,5-P3-sensitive store
      containing relatively few Ca2+ pumps but possessing a relatively high Ca2+ uptake
      capacity, which may reflect the presence of a substantial amount of Ca2+ binding
      protein; and (ii) an Ins-1,4,5-P3-insensitive Ca2+ store containing relatively
      many Ca2+ pumps but possessing a relatively low Ca2+ uptake capacity, which may
      reflect the presence of little if any Ca2+ binding protein. The data presented
      are consistent with the idea of a heterogeneous distribution of Ca2+ pumps, Ca2+
      binding proteins and Ca2+ release channels between intracellular Ca2+ storage
      organelles.

PMID- 7736566
TI  - Introduction of calcium buffers into the cytosol of Dictyostelium discoideum
      amoebae alters cell morphology and inhibits chemotaxis.
AB  - Differentiating Dictyostelium discoideum amoebae respond chemotactically towards
      the attractant cAMP. To test whether chemotaxis requires the establishment of a
      spatial gradient of the cytosolic calcium concentration ([Ca2+]i) we scrape
      loaded calcium chelating agents with different affinities for Ca2+ into the
      cytosol of the cells. The buffers were 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'
      tetraacetic acid (BAPTA) and its derivatives. Parameters analyzed were general
      cell morphology and the capability to protrude pseudopods and to migrate towards
      a cAMP-filled capillary. The chelators dose- and time-dependently inhibited
      spreading of the amoebae on the substrate. Both oriented pseudopod formation and
      locomotion of the cells were reduced. This effect was overcome by extracellular
      Ca2+, but not Mg2+. The effects of BAPTA derivatives were compared to the
      inhibition by BAPTA. A dose-response curve was obtained; 5,5'-difluoro-BAPTA was
      the most potent analogue. We conclude that a [Ca2+]i-gradient is necessary for
      orientation and locomotion. Chemotaxis experiments performed in the presence of
      extracellular EGTA revealed that liberation of Ca2+ from intracellular stores is
      sufficient for pseudopod formation; yet under physiological conditions influx of
      extracellular Ca2+ is also used to establish the gradient.

PMID- 7736567
TI  - Cyclin ubiquitination: the destructive end of mitosis.

PMID- 7736568
TI  - The intracellular localization of messenger RNAs.
AB  - As I hope this review has made clear, mRNA localization plays an important role
      in directing specific proteins to their correct position within a cell. Although
      the study of this process is still in its infancy, it is already apparent that
      there are several ways that mRNAs can be targeted to particular subcellular
      sites. However, the molecular mechanisms responsible for these different
      localization pathways are still largely obscure, and their elucidation must await
      the identification of the specific factors that mediate the interactions between
      the localized mRNAs and more general components such as the cytoskeleton. Most
      examples of localized mRNAs are likely to share several common features. First,
      the site of localization will be determined by the preexisting polarity of the
      cell, and this will most often depend on the organization of the cytoskeleton,
      either directly, in the case of active transport, or indirectly, when
      localization is mediated by localized anchoring sites or stability factors.
      Second, mRNA localization is likely to be tightly coupled to translational
      control. If it is important for a cell to synthesize a protein in a particular
      place, then the translation of the mRNA must be repressed until it is localized.
      Indeed, there are already several examples where the direct linkage between
      translational control and localization has been demonstrated, and these are
      discussed in the accompanying review by Curtis et al. (1995).

PMID- 7736569
TI  - Translational regulation in development.

PMID- 7736570
TI  - Degradation of mRNA in eukaryotes.
AB  - Based on the above mechanisms of mRNA degradation, an integrated model of mRNA
      turnover can be proposed (Figure 1). In this model, all polyadenylated mRNAs
      would be degraded by the deadenylation-dependent pathway at some rate. In
      addition to this default pathway, another layer of complexity would come from
      degradation mechanisms specific to individual mRNAs or to classes of mRNAs. Such
      mRNA-specific mechanisms would include sequence-specific endonuclease cleavage
      and deadenylation-independent decapping. Thus, the overall decay rate of an
      individual transcript will be a function of its susceptibility to these turnover
      pathways. In addition, cis-acting sequences that specify mRNA decay rate, as well
      as regulatory inputs that control mRNA turnover, are likely to affect all the
      steps of these decay pathways. One important goal in future work will be to
      identify the gene products that are responsible for the nucleolytic events in
      these pathways and to delineate how specific mRNA features act to affect the
      function of these degradative activities. The identification of distinct mRNA
      decay pathways should allow, genetic and biochemical approaches that can be
      designed to identify these gene products. A second important goal is to
      understand the nature of the interaction between the 5' and 3' termini, which may
      also be critical for efficient translation.

PMID- 7736571
TI  - Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that
      has acquired a novel RNA-binding motif at its active site.
AB  - The site-specific C to U editing of apolipoprotein B100 (apoB100) mRNA requires a
      27 kDa protein (p27) with homology to cytidine deaminase. Here, we show that p27
      is a zinc-containing deaminase, which operates catalytically like the E. coli
      enzyme that acts on monomeric substrate. In contrast with the bacterial enzyme
      that does not bind RNA, p27 interacts with its polymeric apoB mRNA substrate at
      AU sequences adjacent to the editing site. This interaction is necessary for
      editing. RNA binding is mediated through amino acid residues involved in zinc
      coordination, in proton shuttling, and in forming the alpha beta alpha structure
      that encompasses the active site. However, certain mutations that inactivate the
      enzyme do not affect RNA binding. Thus, RNA binding does not require a
      catalytically active site. The acquisition of polymeric substrate binding
      provides a route for the evolution of this editing enzyme from one that acts on
      monomeric substrates.

PMID- 7736572
TI  - The protein-conducting channel in the membrane of the endoplasmic reticulum is
      open laterally toward the lipid bilayer.
AB  - Lipids and proteins were found to contact a nascent type II membrane protein, as
      well as a nascent secretory protein, during their insertion into the membrane of
      the endoplasmic reticulum. This suggests that the protein-conducting channel is
      open laterally toward the lipid bilayer during an early stage of protein
      insertion. Contact to lipids was confined to the hydrophobic core region of the
      respective signal or signal anchor sequence. Thus, the nascent polypeptide is
      positioned in the translocation complex such that the signal or signal anchor
      sequence faces the lipid bilayer, whereas the hydrophilic, translocating portion
      is in proteinaceous environment.

PMID- 7736573
TI  - The peptide repeat domain of nucleoporin Nup98 functions as a docking site in
      transport across the nuclear pore complex.
AB  - We report the cDNA deduced primary structure of a wheat germ agglutinin-reactive
      nuclear pore complex (NPC) protein of rat. The protein, termed Nup98 (for
      nucleoporin of 98 kDa), contains numerous GLFG and FG repeats and some FXFG
      repeats and is thus a vertebrate member of a family of GLFG nucleoporins that
      were previously discovered in yeast. Immunoelectron microscopy showed Nup98 to be
      asymmetrically located at the nucleoplasmic side of the NPC. Nup98 functions as
      one of several docking site nucleoporins in a cytosolic docking activity-mediated
      binding of a model transport substrate. The docking site of Nup98 was mapped to
      its N-terminal half, which contains all of the peptide repeats. A recombinant
      segment of this region depleted the docking activity of cytosol. We suggest that
      the peptide repeat domain of Nup98, together with peptide repeat domains of other
      nucleoporins, forms an array of sites for mediated docking of transport
      substrate, and that bidirectional transport across the NPC proceeds by repeated
      docking and undocking reactions.

PMID- 7736574
TI  - Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck
      cooperate in hematopoietic cell proliferation.
AB  - Two interleukin-2 receptor-dependent signaling pathways have thus far been
      identified: the c-fos/c-jun induction pathway mediated by src family protein
      tyrosine kinases and the c-myc induction pathway. Here, we provide evidence for
      the existence of a third, rapamycin-sensitive pathway, which results in the
      induction of another proto-oncogene, bcl-2. In the hematopoietic cell line BAF
      B03, the expression of any two of lckF505 (an active form of p56lck), Bcl-2, or c
      Myc is sufficient to promote transit of the cell cycle, regardless of the
      activation state of the third pathway. We also provide evidence that epidermal
      growth factor receptor signaling may act through the same pathway that involves
      p56lck. These studies demonstrate a novel approach to dissecting signaling
      pathways regulating cellular proliferation.

PMID- 7736575
TI  - Gene targeting of BPAG1: abnormalities in mechanical strength and cell migration
      in stratified epithelia and neurologic degeneration.
AB  - BPAG1 is the major antigenic determinant of autoimmune sera of bullous pemphigoid
      (BP) patients. It is made by stratified squamous epithelia, where it localizes to
      the inner surface of specialized integrin-mediated adherens junctions
      (hemidesmosomes). To explore the function of BPAG1 and its relation to BP, we
      targeted the removal of the BPAG1 gene in mice. Hemidesmosomes are otherwise
      normal, but they lack the inner plate and have no cytoskeleton attached. Though
      not affecting cell growth or substratum adhesion, this compromises mechanical
      integrity and influences migration. Unexpectedly, the mice also develop severe
      dystonia and sensory nerve degeneration typical of dystonia musculorum (dt/dt)
      mice. We show that in at least one other strain of dt/dt mice, BPAG1 gene is
      defective.

PMID- 7736576
TI  - Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar
      long-term depression in GluR delta 2 mutant mice.
AB  - Of the six glutamate receptor (GluR) channel subunit families identified by
      molecular cloning, five have been shown to constitute either the AMPA, kainate,
      or NMDA receptor channel, whereas the function of the delta subunit family
      remains unknown. The selective localization of the delta 2 subunit of the GluR
      delta subfamily in cerebellar Purkinje cells prompted us to examine its possible
      physiological roles by the gene targeting technique. Analyses of the GluR delta 2
      mutant mice reveal that the delta 2 subunit plays important roles in motor
      coordination, formation of parallel fiber-Purkinje cell synapses and climbing
      fiber-Purkinje cell synapses, and long-term depression of parallel fiber-Purkinje
      cell synaptic transmission. These results suggest a close relationship between
      synaptic plasticity and synapse formation in the cerebellum.

PMID- 7736577
TI  - Sgs1: a eukaryotic homolog of E. coli RecQ that interacts with topoisomerase II
      in vivo and is required for faithful chromosome segregation.
AB  - Topoisomerase II (topo II) catalyzes the decatenation of interlinked DNA
      molecules and is essential for chromosome segregation. To test the hypothesis
      that the noncatalytic C-terminal domain of topo II is necessary for mediating
      interactions with other proteins required for chromosome segregation, we used a
      two-hybrid cloning strategy to identify proteins that interact with S. cerevisiae
      topo II in vivo. One protein identified (Sgs1p) is structurally related to E.
      coli RecQ protein and contains helicase signature motifs. Strains lacking Sgs1p
      exhibit elevated levels of chromosome misseggregation during both mitotic and
      meiotic division. We propose a model to account for the interaction of a
      topoisomerase and a helicase in the faithful segregation of newly replicated
      eukaryotic chromosomes.

PMID- 7736578
TI  - CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is
      essential for the metaphase to anaphase transition.
AB  - We have isolated cDNAs and raised antibodies corresponding to the human homologs
      of the S. cerevisiae CDC27 and CDC16 proteins, which are tetratrico peptide
      repeat (TPR)-containing proteins essential for mitosis in budding yeast. We find
      that the CDC27Hs and CDC16Hs proteins colocalize to the centrosome at all stages
      of the mammalian cell cycle, and to the mitotic spindle. Injection of affinity
      purified anti-CDC27Hs antibodies into logarithmically growing HeLa cells causes a
      highly reproducible cell cycle arrest in metaphase with apparently normal spindle
      structure. We conclude that CDC27 and CDC16 are evolutionarily conserved
      components of the centrosome and mitotic spindle that control the onset of
      postmetaphase events during mitosis.

PMID- 7736579
TI  - Genes involved in sister chromatid separation are needed for B-type cyclin
      proteolysis in budding yeast.
AB  - B-type cyclin destruction is necessary for exit from mitosis and the initiation
      of a new cell cycle. Through the isolation of mutants, we have identified three
      essential yeast genes, CDC16, CDC23, and CSE1, which are required for proteolysis
      of the B-type cyclin CLB2 but not of other unstable proteins. cdc23-1 mutants are
      defective in both entering and exiting anaphase. Their failure to exit anaphase
      can be explained by defective cyclin proteolysis. CDC23 is required at the
      metaphase/anaphase transition to separate sister chromatids, and we speculate
      that it might promote proteolysis of proteins that hold sister chromatids
      together. Proteolysis of CLB2 is initiated in early anaphase, but a fraction of
      CLB2 remains stable until anaphase is complete.

PMID- 7736580
TI  - A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific
      conjugation of ubiquitin to cyclin B.
AB  - Cyclin B is degraded at the onset of anaphase by a ubiquitin-dependent
      proteolytic system. We have fractionated mitotic Xenopus egg extracts to identify
      components required for this process. We find that UBC4 and at least one other
      ubiquitin-conjugating enzyme can support cyclin B ubiquitination. The mitotic
      specificity of cyclin ubiquitination is determined by a 20S complex that contains
      homologs of budding yeast CDC16 and CDC27. Because these proteins are required
      for anaphase in yeast and mammalian cells, we refer to this complex as the
      anaphase-promoting complex (APC). CDC27 antibodies deplete APC activity, while
      immunopurified CDC27 complexes are sufficient to complement either interphase
      extracts or a mixture of recombinant UBC4 and the ubiquitin-activating enzyme E1.
      These results suggest that APC functions as a regulated ubiquitin-protein ligase
      that targets cyclin B for destruction in mitosis.

PMID- 7736581
TI  - Polycystic kidney disease: the complete structure of the PKD1 gene and its
      protein. The International Polycystic Kidney Disease Consortium.
AB  - Mutations in the PKD1 gene are the most common cause of autosomal dominant
      polycystic kidney disease (ADPKD). Other PKD1-like loci on chromosome 16 are
      approximately 97% identical to PKD1. To determine the authentic PKD1 sequence, we
      obtained the genomic sequence of the PKD1 locus and assembled a PKD1 transcript
      from the sequence of 46 exons. The 14.5 kb PKD1 transcript encodes a 4304 amino
      acid protein that has a novel domain architecture. The amino-terminal half of the
      protein consists of a mosaic of previously described domains, including leucine
      rich repeats flanked by characteristic cysteine-rich structures, LDL-A and C-type
      lectin domains, and 14 units of a novel 80 amino acid domain. The presence of
      these domains suggests that the PKD1 protein is involved in adhesive protein
      protein and protein-carbohydrate interactions in the extracellular compartment.
      We propose a hypothesis that links the predicted properties of the protein with
      the diverse phenotypic features of ADPKD.

PMID- 7736582
TI  - A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG
      encodes the IKr potassium channel.
AB  - Mutations in HERG cause an inherited cardiac arrhythmia, long QT syndrome (LQT).
      To define the function of HERG, we expressed the protein in Xenopus oocytes. The
      biophysical properties of expressed HERG are nearly identical to the rapidly
      activating delayed rectifier K+ current (IKr) in cardiac myocytes. HERG current
      is K+ selective, declines with depolarizations above 0 mV, is activated by
      extracellular K+, and is blocked by lanthanum. Interestingly, HERG current is not
      blocked by drugs that specifically block IKr in cardiac myocytes. These data
      indicate that HERG proteins form IKr channels, but that an additional subunit may
      be required for drug sensitivity. Since block of IKr is a known mechanism for
      drug-induced cardiac arrhythmias, the finding that HERG encodes IKr channels
      provides a mechanistic link between certain forms of inherited and acquired LQT.

PMID- 7736583
TI  - The role of N-glycans in the secretory pathway.

PMID- 7736584
TI  - The long and short of hedgehog signaling.

PMID- 7736585
TI  - The retinoblastoma protein and cell cycle control.

PMID- 7736586
TI  - Comparison of recombination in vitro and in E. coli cells: measure of the
      effective concentration of DNA in vivo.
AB  - Despite the extremely high concentration of DNA in nucleoid/nuclear regions,
      chromosomal dimerization and entanglement are avoided. To help understand this,
      we measured the effective concentration of DNA in E. coli, a value that reflects
      the functional impact of the cellular milieu on DNA site reactivity. We used as
      probes plasmid fusion reactions by two site-specific recombinases. The normalized
      extents and rates of fusion in these systems were much lower in vivo than in
      analogous in vitro reactions. We calculate that the effective concentration of
      plasmid DNA is about one order of magnitude lower than the chemical
      concentration. We suggest that in bacterial cells DNA accessibility is highly
      restricted and that this dominates the forces that increase DNA activity, such as
      macromolecular crowding.

PMID- 7736587
TI  - Coupling between transcription termination and RNA polymerase inchworming.
AB  - Advancement of RNA polymerase of E. coli occurs in alternating laps of monotonic
      and inchworm-like movement. Cycles of inchworming are encoded in DNA and involve
      straining and relaxation of the ternary complex accompanied by characteristic
      leaping of DNA and RNA footprints. We demonstrate that the oligo(T) tract that
      constitutes a normal part of transcription terminators acts as an inchworming
      signal so that the leap coincides with the termination event. Prevention of
      leaping with a roadblock of cleavage-defective EcoRI protein results in
      suppression of RNA chain release at a termination site. The results indicate that
      straining and relaxation of RNA polymerase are steps in the termination
      mechanism.

PMID- 7736588
TI  - Contact with a component of the polymerase II holoenzyme suffices for gene
      activation.
AB  - In yeast strains bearing the point mutation called GAL11P (for potentiator),
      certain GAL4 derivatives lacking any classical activating region work as strong
      activators. The P mutation confers upon GAL11, a component of the RNA polymerase
      II holoenzyme, the ability to interact with a portion of the dimerization region
      of GAL4. The region of GAL11 affected by the P mutation is evidently functionally
      inert in ordinary cells, suggesting that this mutation is of no functional
      significance beyond creating an artificial target for the GAL4 dimerization
      fragment. From these observations and further analyses of GAL11, we propose that
      a single activator-holoenzyme contact can trigger gene activation simply by
      recruiting the latter to DNA.

PMID- 7736589
TI  - The anatomy of a bifunctional enzyme: structural basis for reduction of oxygen to
      water and synthesis of nitric oxide by cytochrome cd1.
AB  - Cytochrome cd1-nitrite reductase is a bifunctional enzyme that catalyzes the one
      electron reduction of nitrite to nitric oxide and the four-electron reduction of
      oxygen to water. The 1.55 A crystal structure of the dimeric enzyme from
      Thiosphaera pantotropha is reported here. The protein was sequenced from the X
      ray structure. Each subunit contains a covalent c heme with two axial His ligands
      (His-17, His-69) and a unique noncovalent d1 heme ligated by Tyr-25 and His-200.
      The d1 heme is the mononuclear iron center where both oxygen and nitrite
      reduction take place. The two types of heme are located in separate domains whose
      arrangement suggests a mechanism requiring domain movement during catalysis.

PMID- 7736590
TI  - The FIP1 gene encodes a component of a yeast pre-mRNA polyadenylation factor that
      directly interacts with poly(A) polymerase.
AB  - We have identified an essential gene, called FIP1, encoding a 327 amino acid
      protein interacting with yeast poly(A) polymerase (PAP1) in the two-hybrid assay.
      Recombinant FIP1 protein forms a 1:1 complex with PAP1 in vitro. At 37 degrees C,
      a thermosensitive allele of FIP1 shows a shortening of poly(A) tails and a
      decrease in the steady-state level of actin transcripts. When assayed for 3'-end
      processing in vitro, fip1 mutant extracts exhibit normal cleavage activity, but
      fail to polyadenylate the upstream cleavage product. Polyadenylation activity is
      restored by adding polyadenylation factor I (PF I). Antibodies directed against
      FIP1 specifically recognize a polypeptide in these fractions.
      Coimmunoprecipitation experiments reveal that RNA14, a subunit of cleavage factor
      I (CF I), directly interacts with FIP1, but not with PAP1. We propose a model in
      which PF I tethers PAP1 to CF I, thereby conferring specificity to poly(A)
      polymerase for pre-mRNA substrates.

PMID- 7736591
TI  - Subnuclear localization of WT1 in splicing or transcription factor domains is
      regulated by alternative splicing.
AB  - WT1 is a tumor suppressor gene with a key role in urogenital development and the
      pathogenesis of Wilms' tumor. Two alternative splice sites in the WT1 transcript
      allow the gene to encode four proteins. These carry four Kruppel-type zinc
      fingers and to date have primarily been implicated in transcriptional control of
      genes involved in growth regulation. However, here we demonstrate colocalization
      of WT1 with splicing factors in the fetal kidney and testis and in expressing
      cell lines. Using immunoprecipitation, we show that two WT1 isoforms directly
      associate with one or a limited number of components in the spliceosomes and
      coiled bodies. Moreover, COS cell expression studies suggest that alternative
      splicing within the WT1 zinc finger region determines whether the protein
      localizes mainly with splicing factors or with DNA in transcription factor
      domains in the nucleus. We propose that WT1 plays roles in posttranscriptional
      processing of RNA as well as in transcription.

PMID- 7736592
TI  - Translational regulation of oskar mRNA by bruno, an ovarian RNA-binding protein,
      is essential.
AB  - Oskar (osk) protein directs the deployment of nanos (nos), the posterior body
      patterning morphogen in Drosophila. To avoid inappropriate activation of nos, osk
      activity must appear only at the posterior pole of the oocyte, where the osk mRNA
      becomes localized during oogenesis. Here, we show that translation of osk mRNA
      is, and must be, repressed prior to its localization; absence of repression
      allows osk protein to accumulate throughout the oocyte, specifying posterior body
      patterning throughout the embryo. Translational repression is mediated by an
      ovarian protein, bruno, that binds specifically to bruno response elements
      (BREs), present in multiple copies in the osk mRNA 3'UTR. Addition of BREs to a
      heterologous mRNA renders it sensitive to translational repression in the ovary.

PMID- 7736593
TI  - Evidence for a NIMA-like mitotic pathway in vertebrate cells.
AB  - NIMA is essential for entry into mitosis in Aspergillus nidulans. To examine
      whether there is a NIMA-like pathway in other eukaryotic cell cycles, we
      expressed NIMA and its dominant negative mutants in two different eukaryotic
      systems. In Xenopus oocytes, NIMA induced germinal vesicle breakdown without
      activating Mos, CDC2, or MAP kinase. In HeLa cells, NIMA induced premature
      mitotic events without activating CDC2, whereas the mutants caused a specific G2
      arrest but did not block mutant CDC2T14AY15F-induced premature entry into
      mitosis. A sequence essential for both these phenotypes was mapped to a region of
      approximately 100 amino acids lying just after the catalytic domain of NIMA that
      shows a significant similarity to protein interaction domains in other proteins.
      These results provide evidence for the existence of a NIMA-like mitotic pathway
      in vertebrate cells.

PMID- 7736594
TI  - Glucose trimming and reglucosylation determine glycoprotein association with
      calnexin in the endoplasmic reticulum.
AB  - To determine the role of N-linked oligosaccharides in the folding of
      glycoproteins, we analyzed the processing of in vitro translated influenza
      hemagglutinin (HA) in dog pancreas microsomes. We found that binding to calnexin,
      a membrane-bound molecular chaperone, was specific to molecules that possessed
      monoglucosylated core glycans. In the microsomes, these were generated either by
      glucose removal from the original triglucosylated core oligosaccharide by
      glucosidases I and II or by reglucosylation of already unglucosylated high
      mannose glycans. Release of fully folded HA from calnexin required the removal of
      the remaining glucose by glucosidase II. The results provided an explanation for
      trimming and reglucosylation activities in the endoplasmic reticulum and
      established a direct correlation between glycosylation and folding.

PMID- 7736595
TI  - Neuroligin 1: a splice site-specific ligand for beta-neurexins.
AB  - Neurexins are neuronal cell surface proteins with hundreds of isoforms generated
      by alternative splicing. Here we describe neuroligin 1, a neuronal cell surface
      protein that is enriched in synaptic plasma membranes and acts as a splice site
      specific ligand for beta-neurexins. Neuroligin 1 binds to beta-neurexins only if
      they lack an insert in the alternatively spliced sequence of the G domain, but
      not if they contain an insert. The extracellular sequence of neuroligin 1 is
      composed of a catalytically inactive esterase domain homologous to
      acetylcholinesterase. In situ hybridization reveals that alternative splicing of
      neurexins at the site recognized by neuroligin 1 is highly regulated. These
      findings support a model whereby alternative splicing of neurexins creates a
      family of cell surface receptors that confers interactive specificity onto their
      resident neurons.

PMID- 7736596
TI  - Floor plate and motor neuron induction by different concentrations of the amino
      terminal cleavage product of sonic hedgehog autoproteolysis.
AB  - The differentiation of floor plate cells and motor neurons can be induced by
      Sonic hedgehog (SHH), a secreted signaling protein that undergoes autoproteolytic
      cleavage to generate amino- and carboxy-terminal products. We have found that
      both floor plate cells and motor neurons are induced by the amino-terminal
      cleavage product of SHH (SHH-N). The threshold concentration of SHH-N required
      for motor neuron induction is about 5-fold lower than that required for floor
      plate induction. Higher concentrations of SHH-N can induce floor plate cells at
      the expense of motor neuron differentiation. Our results suggest that the
      induction of floor plate cells and motor neurons by the notochord in vivo is
      mediated by exposure of neural plate cells to different concentrations of the
      amino-terminal product of SHH autoproteolytic cleavage.

PMID- 7736597
TI  - Long-range sclerotome induction by sonic hedgehog: direct role of the amino
      terminal cleavage product and modulation by the cyclic AMP signaling pathway.
AB  - A long-range signal encoded by the Sonic hedgehog (Shh) gene has been implicated
      as the ventral patterning influence from the notochord that induces sclerotome
      and represses dermomyotome in somite differentiation. Long-range effects of
      hedgehog (hh) signaling have been suggested to result either from local induction
      of a secondary diffusible signal or from the direct action of the highly
      diffusible carboxy-terminal product of HH autoproteolytic cleavage. Here we
      provide evidence that the long-range somite patterning effects of SHH are instead
      mediated by a direct action of the amino-terminal cleavage product. We also show
      that pharmacological manipulations to increase the activity of cyclic AMP
      dependent protein kinase A can selectively antagonize the effects of the amino
      terminal cleavage product. Our results support the operation of a single
      evolutionarily conserved signaling pathway for both local and direct long-range
      inductive actions of HH family members.

PMID- 7736598
TI  - Tequila production.
AB  - Tequila is obtained from the distillation of fermented juice of agave plant,
      Agave tequilana, to which up to 49% (w/v) of an adjunct sugar, mainly from cane
      or corn, could be added. Agave plants require from 8 to 12 years to mature and
      during all this time cleaning, pest control, and slacken of land are required to
      produce an initial raw material with the appropriate chemical composition for
      tequila production. Production process comprises four steps: cooking to hydrolyze
      inulin into fructose, milling to extract the sugars, fermentation with a strain
      of Saccharomyces cerevisiae to convert the sugars into ethanol and organoleptic
      compounds, and, finally, a two-step distillation process. Maturation, if needed,
      is carried out in white oak barrels to obtain rested or aged tequila in 2 or 12
      months, respectively.

PMID- 7736599
TI  - Production and secretion of proteins by streptomycetes.
AB  - Streptomycetes produce a large number of extracellular enzymes as part of their
      saprophytic mode of life. Their ability to synthesize enzymes as products of
      their primary metabolism could lead to the production of many proteins of
      industrial importance. The development of high-yielding expression systems for
      both homologous and heterologous gene products is of considerable interest. In
      this article, we review the current knowledge on the various factors that affect
      the production and secretion of proteins by streptomycetes and try to evaluate
      the suitability of these bacteria for the large-scale production of proteins of
      industrial importance.

PMID- 7736600
TI  - Recent advances in the physiology and genetics of amino acid-producing bacteria.
AB  - Corynebacterium glutamicum and its close relatives, C. flavum and C.
      lactofermentum, have been used for over 3 decades in the industrial production of
      amino acids by fermentation. Since 1984, several research groups have started
      programs to develop metabolic engineering principles for amino acid-producing
      Corynebacterium strains. Initially, the programs concentrated on the isolation of
      genes encoding (deregulated) biosynthetic enzymes and the development of general
      molecular biology tools such as cloning vectors and DNA transfer methods. With
      most of the genes and tools now available, recombinant DNA technology can be
      applied in strain improvement. To accomplish these improvements, it is critical
      and advantageous to understand the mechanisms of gene expression and regulation
      as well as the biochemistry and physiology of the species being engineered. This
      review explores the advances made in the understanding and application of amino
      acid-producing bacteria in the early 1990s.

PMID- 7736601
TI  - Reversions to respiratory competence of omnipotent sup45 suppressor mutants may
      be caused by secondary sup45 mutations.
AB  - The molecular nature of the sup45 respiratory deficient omnipotent suppressor,
      and of three reversions to respiratory competence which removed the suppressor
      effect of the initial mutation, was examined. All reversions were caused by
      secondary sup45 mutations which indicates a direct connection between sup45
      "respiratory" and "translational" functions. Computer analysis showed the local
      changes of Sup45 protein characteristics in the suppressor strain and revertants
      in comparison to the wild-type protein. The distribution of mutant sites in
      relation to evolutionary conserved, and tentatively functional, regions in the
      Sup45 protein is discussed.

PMID- 7736602
TI  - Abnormal growth induced by expression of HBsAg in the secretion pathway of S.
      cerevisiae pep4 mutants.
AB  - The toxicity of HBsAg in the secretion pathway of pep4 strains can be
      progressively reduced in modified SD media containing lower concentrations of
      ammonium sulphate. A procedure, combining a reduction of ammonium sulphate
      concentration in SD media with the disruption of the PEP4 gene of the host
      strain, was developed to enrich transformants which are not inhibited by HBsAg
      expressed in the secretion pathway. Abnormal growth of these non-inhibited
      transformants is characterized by the enlargement of cell morphology, a
      transition to pseudohyphal-like growth in nitrogen-starved media, an increase in
      HBsAg particle production, and the enhancement of growth rate in liquid media.
      This suggests a new approach to overcoming the toxicity of heterologous protein
      in the yeast secretion pathway.

PMID- 7736604
TI  - Evidence for a branched pathway in the polarized cell division of Saccharomyces
      cerevisiae.
AB  - Cells of Saccharomyces cerevisiae can choose a bud site in one of two different
      spatial patterns (axial or bipolar) determined by their mating type. Genes
      important for bud-site selection have been identified and a linear model
      describing the hierarchy of these genes was proposed. We have uncovered a new
      class of genes which is required only for the bipolar pattern. The phenotype of
      the corresponding mutants coupled with epistasis experiments with some budding
      mutants already described suggest the existence of specific genes for the bipolar
      pathway.

PMID- 7736603
TI  - The PSO4 gene of S. cerevisiae is important for sporulation and the meiotic DNA
      repair of photoactivated psoralen lesions.
AB  - We have evaluated the effect of the Saccharomyces cerevisiae pso4-1 mutation in
      sporulation and DNA repair during meiosis. We have found that pso4-1 cells were
      arrested in an early step of meiosis, before premeiotic DNA synthesis, and hence
      did not produce spores. These results suggest that the PSO4 gene may act at the
      start point of the cell cycle, as do some SPO and CDC genes. The pso4-1 mutant
      cells are specifically sensitive to 8-MOP- and 3-CPs-photoinduced lesions, and
      are found to be severely affected in meiotic recombination as well as impaired in
      the mutagenic response, as previously described for mitosis. This means that the
      PSO4 gene is important for the repair 8-MOP-photoinduced lesions, mainly double
      strand breaks, and the processing of these lesions into recombinogenic
      intermediates.

PMID- 7736605
TI  - Determination of chromosome copy numbers in Saccharomyces cerevisiae strains via
      integrative probe and blot hybridization techniques.
AB  - Methods have been devised for analyzing chromosome copy numbers in S. cerevisiae
      strains that may be polyploid or aneuploid, as is apparent in the case of many
      industrial strains. The initial step involved transformation of a strain with an
      integrative "ploidy probe" transplacement fragment that enabled the copy number
      of the targeted chromosomal locus to be determined via genomic Southern blotting
      and quantitative probe hybridization. Dual probe co-hybridization to Southern
      genomic DNA blots was used to extend such locus copy number determinations to
      other loci within the same chromosome, thereby screening for internal consistency
      along the length of the chromosome. This approach was also used to extend the
      analysis to other chromosomes in the genome. The method was established and
      verified with euploid series laboratory strains and then used to examine
      chromosome copy numbers in three industrial strains. One brewing strain
      apparently contained three copies of the chromosomes tested, whilst another
      brewing and a baking strain showed evidence of aneuploidy.

PMID- 7736606
TI  - A kluyveromyces lactis gene homologue to AAC2 complements the Saccaromyces
      cerevisiae op1 mutation.
AB  - A mutation (op1) in the Saccharomyces cerevisiae AAC2 gene, which codes for the
      most abundant ADP/ATP carrier isoform, results in lack of mitochondrial-dependent
      growth and in an as yet unexplained petite-negative phenotype. A gene from the
      petite-negative yeast Kluyveromyces lactis has been isolated by complementing in
      multicopy the op1 mutation of S. cerevisiae. This gene, designated KIAAC, can
      complement the petite-negative phenotype of op1 as well as its inability to grow
      on nonfermentable carbon sources. KIAAC contains a 915-base pair open reading
      frame coding for a protein of 305 amino acids which shows a high degree of
      identity to AAC2. The K. lactis ADP/ATP carrier also shares identity with other
      known ADP/ATP carrier sequences. In particular, the degree of identity of KIAAC
      is higher with the Neurospora crassa carrier (80.1%) than with AAC1 (76.6%). The
      nucleotide sequence upstream of the KIAAC coding region was found to contain a
      long DNA segment with no coding potential, but presenting features of highly
      regulated promoter sequences.

PMID- 7736607
TI  - The suv3 nuclear gene product is required for the in vivo processing of the yeast
      mitochondrial 21s rRNA transcripts containing the r1 intron.
AB  - We have constructed a yeast mitochondrial genome containing only one group-I
      intron, r1, from the 21s rRNA gene and introduced this genome into a strain
      bearing a disruption of the suv3 gene. The presence of the r1 intron alone causes
      a block in respiration, while the isogenic strain containing the intronless
      genome is respiratory competent. Northern analysis indicates that the functional
      suv3 protein is necessary for the yeast cell in order to process the r1
      containing transcripts: in the absence of the suv3 protein the hybridization
      pattern of the excised r1 intron is altered and the amount of mature 21s rRNA is
      50-fold lower. We suggest that the multifunctional suv3 protein, which displays
      motifs of ATP-dependent RNA helicases, is necessary for the in vivo pathway
      leading to formation of mature 21s rRNA from the transcripts containing the r1
      intron in mitochondria of Saccharomyces cerevisiae.

PMID- 7736608
TI  - Organisation and sequence analysis of nuclear-encoded 5s ribosomal RNA genes in
      cryptomonad algae.
AB  - Southern hybridisation, polymerase chain reaction (PCR), and nucleotide sequence,
      data indicate that the 5s ribosomal RNA (rRNA) gene is linked to the main rRNA
      gene repeat in the nuclear genome of four cryptomonad algae (Rhinomonas pauca,
      Storeatula major, Komma caudata, and isolate Cs 134). The 5s gene is apparently
      transcribed in the same direction as the large and small subunit rRNA genes. The
      intergenic spacer between the 5s gene and the large subunit rRNA gene exhibits
      length and sequence polymorphism among the different species. Cryptomonads
      contain two different eukaryotic genomes: the host nucleus and the nucleus of a
      eukaryotic endosymbiont. Mapping experiments with isolated chromosomes of the
      host and endosymbiont genomes showed that the intergenic spacer between the large
      subunit and the 5s rRNA gene, which was amplified from total DNA by PCR, was
      derived from the host nuclear genome.

PMID- 7736609
TI  - Use of URA3 as a reporter of gene expression in C. albicans.
AB  - The C. albicans URA3 gene was tested as a reporter of gene expression. An
      integrating vector was constructed which contained ADE2 as a selectable marker
      together with a truncated form of URA3 lacking the first three codons. A DNA
      fragment containing the promoter and the first 90 codons of the C. albicans CEF3
      gene was inserted into the unique XhoI site 5' to URA3 in order to provide an in
      frame translational fusion. The functionality of the fusion gene was tested
      following integration of a single copy of the plasmid into the ADE2 locus. The
      fusion gene was shown to complement a ura3 deletion mutation and to produce
      orotidine 5'-monophosphate decarboxylase activity (OMP), which is encoded by
      URA3. Expression of the fusion gene was appropriately regulated by the growth
      rate and utilized the same transcriptional start sites as the native CEF3 gene.
      The results demonstrated that URA3 provides a sensitive and versatile reporter
      gene for use in C. albicans.

PMID- 7736610
TI  - Codon usage, genetic code and phylogeny of Dictyostelium discoideum mitochondrial
      DNA as deduced from a 7.3-kb region.
AB  - We have sequenced a region (7,376-bp) of the mitochondrial (mt) DNA (54 kb) of
      the cellular slime mold, Dictyostelium discoideum. From the DNA and amino-acid
      sequence comparisons with known sequences, genes for ATPase subunit 9 (ATP9),
      cytochrome b (CYTB), NADH dehydrogenase subunits 1, 3 and 6 (ND1, ND3 and ND6),
      small subunit rRNA (SSU rRNA) and seven tRNAs (Arg, Asn, Cys, Lys, f-Met, Met and
      Pro) have been identified. The sequenced region of the mtDNA has a high average A
      + T-content (70.8%). The A + T-content of protein-genes (73.6%) is considerably
      higher than that of RNA genes (61.3%). Even with the strong AT-bias, the genetic
      code employed is most probably the universal one. All seven tRNAs are able to
      form typical clover leaf structures. The molecular phylogenetic trees of CYTB and
      SSU rRNA suggest that D. discoideum is closer to green plants than to animals and
      fungi.

PMID- 7736611
TI  - Variable numbers of simple tandem repeats make birds of the order ciconiiformes
      heteroplasmic in their mitochondrial genomes.
AB  - We have analyzed a variable domain of the mitochondrial DNA control region of 18
      avian species. Intra-individual length variation was identified and characterized
      in 15 species. The occurrence of heteroplasmy among species is phylogenetically
      consistent with a current classification of birds. Polymerase chain reaction
      amplifications, direct sequencing, and Southern analysis of mitochondrial DNA
      showed that the heteroplasmy is due to variable numbers of direct repeats in a
      tandem organization, located in the control region close to the tRNAPhe gene. The
      tandem repeats consist of short sequence motifs that vary in size from 4 to 32
      base pairs between species. Sequence complexity of the repeat motifs was low,
      with almost exclusively Ts and Gs in the heavy-strand. Extensive variation in the
      copy number of the repeats was seen both intra-specifically and within
      individuals. This is the first report of mitochondrial heteroplasmy characterized
      at the sequence level in birds.

PMID- 7736612
TI  - A nuclear suppressor overcomes defects in the synthesis of the chloroplast psbD
      gene product caused by mutations in two distinct nuclear genes of Chlamydomonas.
AB  - Mutations in two distinct nuclear genes, called NAC 1 and AC-115, of the
      unicellular green alga Chlamydomonas reinhardtii cause a specific and dramatic
      reduction in the synthesis of the chloroplast-encoded D2 polypeptide of
      Photosystem II. The psbD transcript which encodes the D2 protein is present in
      the mutant strains, but protein pulse-labeling and immunoprecipitation
      experiments demonstrate that the synthesis of the D2 protein does not occur
      normally in these cells. These phenotypes are suppressed by an extragenic nuclear
      suppressor isolated from a pseudorevertant of a nac 1 mutant. This suppressor is
      neither allele- nor gene-specific in its suppression and is able to overcome the
      effects of two different mutations in the NAC 1 gene, as well as a mutation in AC
      115. The suppressor seems to be specific in its ability to remedy blocks in psbD
      mRNA translation in the chloroplast. It is not able to restore the translation of
      another chloroplast-encoded mRNA which is blocked by another nuclear mutation.
      The suppressor may identify a new nuclear gene specifically involved in the
      synthesis of the D2 protein in the chloroplast.

PMID- 7736613
TI  - The trans-spliced intron 1 in the psaA gene of the Chlamydomonas chloroplast: a
      comparative analysis.
AB  - In the secondary structure model that has been proposed for the trans-spliced
      intron 1 in the Chlamydomonas reinhardtii psaA gene, a third RNA species (tscA
      RNA) interacts with the 5' and 3' intron parts flanking the exons to reconstitute
      a composite structure with several features of group-II introns. To test the
      validity of this model, we undertook the sequencing and modelling of equivalent
      introns in the psaA gene from other unicellular green algae belonging to the
      highly diversified genus Chlamydomonas. Our comparative analysis supports the
      model reported for the C. reinhardtii psaA intron 1, and also indicates that the
      5' end of the tscA RNA and the region downstream from the psaA exon 1 cannot be
      folded into a structure typical of domain I as described for most group-II
      introns. It is possible that a fourth RNA species, yet to be discovered, provides
      the parts of domain I which are apparently missing.

PMID- 7736614
TI  - Chloroplast rRNA transcription from structurally different tandem promoters: an
      additional novel-type promoter.
AB  - Identification of transcription initiation sites in the promoter region of the
      tobacco chloroplast rRNA operon has been carried out by ribonuclease protection
      of in vitro capped RNAs and primer extension experiments. A promoter with typical
      chloroplast -10 and -35 motifs (P1) drives initiation of transcription from
      position -116 relative to the mature 16s rRNA sequence. In addition, we have
      found that a second primary transcript starts at position -64. This proximal
      promoter (P2) lacks any elements similar to those reported so far in chloroplast
      promoter regions, and hence P2 represents a novel-type promoter. Both transcripts
      are present in chloroplasts from green leaves and in non-photosynthetic
      proplastids from heterotrophically cultured cells (BY2), but their relative
      amounts appear to differ. The steady state level of the P2 transcript, with
      respect to P1, is higher in BY2 proplastids than in leaf chloroplasts.

PMID- 7736616
TI  - Electrophoretic karyotype of Cercospora kikuchii.
AB  - Classical genetic analyses are not possible with the phytopathogenic fungus
      Cercospora kikuchii since no sexual stage has been identified. To facilitate gene
      mapping and to develop an understanding of the genome organization of C.
      kikuchii, an electrophoretic karyotype has been obtained using contour-clamped
      homogeneous electric field gel electrophoresis (CHEF). Eight chromosomes, two of
      which migrate as a doublet, have been separated into seven bands ranging from 2.0
      to 5.5 Mb. Using this determination of chromosome number and size, the total
      genome size of C. kikuchii is estimated to be 28.4 Mb. In addition, genes
      encoding tubulin, ribosomal DNA, and four previously isolated light-enhanced
      cDNAs from C. kikuchii were assigned to chromosomes by Southern-hybridization
      analysis of CHEF blots.

PMID- 7736615
TI  - The chloroplast trnP-trnW-petG gene cluster in the mitochondrial genomes of Beta
      vulgaris, B. trigyna and B. webbiana: evolutionary aspects.
AB  - The chloroplast trnP-trnW-petG gene cluster has been identified in the
      mitochondrial DNA (mtDNA) of sugar beet (Beta vulgaris). The chloroplast-derived
      trnW gene is transcribed in the mitochondria; the other two genes, however, do
      not seem to be transcribed. This gene cluster is also present in the
      mitochondrial genomes of two wild Beta species, B. trigyna and B. webbiana. Sugar
      beet and the two wild relatives share 100% sequence identity in the coding
      regions of both the mitochondrial trnP and trnW genes. On the other hand, the
      petG genes from the wild Beta mtDNAs were found to be disrupted either by a 5-bp
      duplication (B. trigyna) or by a deletion of the 5' region (B. webbiana). A data
      base search revealed that a conserved sequence of 60 bp is present in the trnP
      trnW intergenic region of the mitochondrial genomes of the three Beta species as
      well as in other higher plants, including wheat and maize, and that the conserved
      sequence is absent from the chloroplast counterpart. Our results thus favour the
      hypothesis of a monophyletic origin of the trnP-trnW-petG cluster found in the
      plant mitochondrial genomes examined.

PMID- 7736617
TI  - [Lactate dehydrogenase activity in the diagnosis of retinoblastoma].
AB  - The authors examined the lactic dehydrogenase activity and that of its isoenzymes
      in a group of 22 orbit with a confirmed diagnosis of retinoblastoma. They
      investigated and evaluate total LDH in the vitreous humour and blood serum and
      the ration of isoenzymes LDH 5 to LDH 1 in the same media. The assembled results
      confirmed that in eyes with retinoblastomas a significant pathological rise not
      only of the total LDH takes place but the response of isoenzymes is even more
      sensitive. The examination is therefore a qualitative asset to the clinical
      diagnosis of retinoblastoma.

PMID- 7736618
TI  - [Planimetric characteristics of the optic papilla in relation to age].
AB  - Percentage relation of the neuroretinal rim area to the total optic disc area was
      examined planimetrically in relation to the age of 116 probands having no optic
      disease and divided into the age decades from 3 to 7. In 3rd decade percentage of
      the neuroretinal rim area was on average 90.26% (min. 81.2; max. 93.6 standard
      deviation 3,225). In 4th decade average area was 89.92% (min. 83.7; max. 96.5
      standard deviation 3,494). In 5th decade average area of the neuroretinal rim
      area was 88.583% (min. 78.6; max. 95.5 standard deviation 4,496). In 7th decade
      average are was 82.448% (min. 73.8; max. 93.5 standard deviation 4,758).
      Significance of the value differences found by means of t-Student non-pair test:
      significant differences were found between the parametres in 3rd and 6th decades
      (p is less than 0.01); between 3rd and 7th decades (p is less than 0.001);
      between 4th and 6th decades (p is less than 0.01); between 4th and 7th decades (p
      is less than 0.001); between 5th and 7th age decades (p is less than 0.001) and
      between 6th and 7th age decades (p is less than 0.01). No significant differences
      were found between the parametres of the age decades 3 and 5, 3 and 4, 4 and 5, 6
      and 7.

PMID- 7736619
TI  - [Functional and morphologic changes in the posterior ocular field in primary open
      angle glaucoma. I. Relation between the fluorescein angiography image of the
      papilla and the c/d ratio].
AB  - In 53 eyes with the primary open angle glaucoma optic disc perfusion condition
      was examined fluoroangiographically in different stages of the pathologic
      process. Findings were divided into the following groups: 1) physiologic
      angiogram, 2) relative transient defect in filling, 3) relative permanent defect
      in filling, 4) absolute defect in filling. According to c/d ratio found the group
      was divided into: 1) c/d from 0.3 to 0.45; 2) from 0.46 to 0.6; 3) c/d from 0.61
      to 0.8; 4) c/d more than 0.8. Statistically significant mutual correlation
      (Friedman's correlation coeficient p = 0.7325) was found in the above mentioned
      stages of the pathologic process examined fluorangiographically and by means of
      the c/d ratio. Thus it was clinically confirmed that in all stages of the
      glaucomatous atrophy of optic disc proportion ratios between capillaries and the
      other tissues remained constant. Important role of vessels played in the genesis
      of glaucomatous atrophy of optic disc was shown.

PMID- 7736620
TI  - [Pars plana vitrectomy in Terson's syndrome].
AB  - Pars plana vitrectomy (PPV) was the operation of choice in haemorrhage (Terson's
      syndrome) in 7 eyes of 5 patients aged 32 to 47 years. The interval between
      intracranial haemorrhage and PPV varied from 2 to 10 months. Patients after PPV
      were followed up for 12 to 84 months. The postoperative course was complicated by
      successfully operated retinal detachment in two eyes where PPV was not
      safeguarded by cerclage. The final visual acuity 0.7-1.0 was achieved in 6 of 7
      eyes (87%); visual acuity of 0.1 in one eye was due to a lamellar defect of the
      macula. PPV is the treatment of choice in Terson's syndrome with bilateral
      haemorrhage into the vitreous body and in massive unilateral extravasation with
      inadequate spontaneous resorption. Cerclage in PPV in TS is according to the
      authors essential prevention of iatrogenic retinal detachment.

PMID- 7736621
TI  - [Anterior uveitis in Lyme borreliosis].
AB  - The authors present an account of two patients with anterior uveitis in the
      second stage of Lyme borreliosis. The draw attention to diagnostic problems of
      the disease from the ophthalmological aspect.

PMID- 7736622
TI  - [Implantation of intraocular lenses simultaneously with surgery for glaucoma].
AB  - The authors' experiences with combined operation ECCE, implantation IOL and
      trabeculectomy are presented. The advantages and disadvantages of various
      operation techniques are discussed here. The suitable conditions for this type of
      operation are defined based on their experiences and literature sources. The
      results are presented at the group of 12 eyes of the patients simultaneously with
      the analysis of per and postoperative complications.

PMID- 7736623
TI  - [Importance of individualizing the formula for improving the accuracy of
      calculating emmetropia in intraocular lenses before cataract surgery].
AB  - The authors evaluated the individualized A-constants of 858 patients. These
      patients were divided into 12 groups according to the surgeon and the type of
      implanted IOL. The valuation of the results showed a marked discrepancy between
      the mean value of the individualized A-constant and the value recommended by the
      manufacturer. In this set of patients the individualization of the formula
      decreased the postoperative refractive error in some cases by 0.4 D for three
      piece lenses and by 1.7 D for one-piece lenses.

PMID- 7736624
TI  - [An increasing trend in cataract surgery in Slovakia (1990-1993)].
AB  - The authors present data obtained in an enquiry from all Ophthalmological Clinics
      and departments in Slovakia which were concerned with surgery of cataract in 1990
      1993. They evaluate the number of cataracts, implanted artificial intraocular
      lenses, the applied surgical methods and types of implanted lenses. During the
      period of investigation the number of operated cataracts increased by 66%, the
      number of implanted lenses increased from 29% to 66.8% of the total number of
      operated cataracts. The number of departments which implant artificial lenses
      increased from 38.7% to 81.8%. The EKEK method is already used in 85%. Slowly
      also the number of phacoemulsifications is rising from 1.9% to 6.2%.

PMID- 7736625
TI  - [Acute monocytic leukemia simulating clinical manifestations of retrobulbar
      neuritis].
AB  - Lesion of optic disc may appear also with coherence to myeloid leukaemia. Authors
      introduce a case report of a patient, who found out help of an ophthalmologist
      with very indefinite difficulties (visual acuity deterioration of her left eye in
      connection with long-lasting sinusitis). Due to changes in orbit and the optic
      disc the status was evaluated as retrobulbar neuritis. During the indicated
      therapy by corticosteroids (Prednison) a steroid gastric ulcer was unfolded.
      During the additional therapy and after the sternal punction the acute monocytic
      leukaemia (AML) was diagnosed. On that base the aimed therapy at the Clinic of
      Haematology was realised. The patient died 27 months since the diagnose of AML
      was determined.

PMID- 7736626
TI  - [200 years since the birth of Josef Ryba (21 March 1795--1 March 1856)].

PMID- 7736627
TI  - [Retinal detachment in pseudophakia].
AB  - The author evaluates the prevalence and results of surgical treatment of retinal
      detachment (RD) after implantation of intraocular lenses in a group of 10,185
      eyes operated at the First and Second Ophthalmological Clinic from 1988 to the
      end of 1993. Retinal detachment was observed in 0.4% of artephakic eyes. A
      striking risk factor for the development of RD was in particular loss of the
      vitreous body during cataract operation, a previous injury, myopia and YAG
      capsulotomy. The presence of an intraocular lens did not influence in a
      substantial way the selection of the surgical procedure. In cases with a
      complicated finding in the anterior segment and the retina the authors selected
      more frequently pars plana vitrectomy (PPV) with internal tamponade with an
      expansive gas or silicone oil (in 44.3% eyes). The retina became attached in
      90.4% of the eyes, while in patients operated by cryosurgery anatomical success
      was achieved in 82.1% of the eyes and in the group operated by PPV with internal
      tamponade in 100% of the eyes. Functional improvement, as compared with the
      condition before surgery of RD, was achieved in 48.9% of successfully operated
      eyes. In the PPV group the authors observed, however, substantially poorer
      functional results as compared with cryosurgery. In complicated artephakic RD PPV
      with internal tamponade contributed to a striking improvement of anatomical
      results but the poorer functional results after PPV in complicated RD provide
      evidence of a poorer prognosis of artephakic RD, as compared with aphakic ones.

PMID- 7736628
TI  - New developments in the understanding of cerebral vasoregulation and vasospasm:
      the endothelin-nitric oxide network.
AB  - Endothelins, which are powerful vasoconstrictors, and nitric oxide, which is a
      powerful vasodilator, together form a balanced system that regulates blood flow
      in the brain and in other organs. Ongoing research may yield new drugs that act
      on this system to prevent or reverse cerebral vasospasm in subarachnoid
      hemorrhage and other conditions. Many compounds are involved in cerebral
      vasoregulation under physiologic and pathologic conditions; of these, endothelins
      and nitric oxide have attracted considerable attention over the last several
      years. Endothelins and nitric oxide differ in chemical structure and
      pharmacological properties: endothelins are potent vasoconstrictor peptides
      consisting of 21 amino acids; nitric oxide is a free radical with a half-life of
      only a few seconds and exerts powerful vasodilatory effects. Both are produced by
      a number of cell types in the brain and interact at various levels to profoundly
      influence cerebral vessel function.

PMID- 7736629
TI  - Acute hospital care of the elderly: minimizing the risk of functional decline.
AB  - Between 25% and 60% of older patients in the hospital undergoing care for an
      acute illness risk some loss of independent physical function. This loss may lead
      to prolonged hospital stay, nursing-home placement, or death. The risk of
      functional decline is related to the hospital environment, as well as to the
      physical frailty of the patient, disease severity, and cognitive impairment. An
      interdisciplinary approach may prevent functional decline. The aim is to modify
      the physical environment, prevent iatrogenic illness, detect and treat functional
      impairments, promote mobility, assess and treat nutritional problems, and address
      the patient's personal needs and values.

PMID- 7736630
TI  - The familial ovarian cancer registry: progress report.
AB  - BACKGROUND: Ovarian cancer can be cured if detected early enough, but usually has
      already metastasized when diagnosed. A family history of ovarian cancer is still
      the strongest known risk factor. OBJECTIVE: To identify women at risk for ovarian
      cancer and design a program of surveillance. METHODS: Prospective registry of
      women with a family history of ovarian cancer. RESULT: From April 1991 to July
      1993, 137 women (119 families), mean age 43, registered with the Familial Ovarian
      Cancer Registry. The 119 pedigrees revealed 171 cases of ovarian cancer. Only one
      family is undocumented by pathology. Forty of 137 registrants have more than one
      relative with ovarian cancer. Six percent of pelvic examinations were abnormal
      for potential adnexal disease. In 4% of registrants, initial CA125 concentrations
      were abnormal. Ultrasound examinations were abnormal in ovarian size (5%), in
      morphology (3%), and by resistive indices (4%). Four ultrasounds were repeated
      earlier than routine. Using "standard" fees, the total cost to diagnose the one
      case of ovarian cancer discovered was $68,848. CONCLUSIONS: This approach still
      cannot be considered cost-effective. We are continuing to search for genetic and
      molecular markers of disease in women at greatest risk and in their affected
      relatives.

PMID- 7736631
TI  - Communication and malpractice: why patients sue their physicians.

PMID- 7736632
TI  - Fever and pleuritis in a postpartum patient.

PMID- 7736633
TI  - Assessing myocardial ischemia, hibernation, and viability: stress
      echocardiography and nuclear imaging.

PMID- 7736634
TI  - Current status of Helicobacter pylori in peptic ulcer disease.
AB  - All patients with documented, past or present gastric or duodenal ulcers and who
      are infected with Helicobacter pylori should undergo antimicrobial therapy to
      eradicate it. Data do not yet support giving antimicrobial therapy to treat
      nonulcer dyspepsia or to prevent gastric neoplasia. H pylori infection is the
      main cause of chronic superficial gastritis and is associated with both gastric
      and duodenal ulcers. However, it has no proven relationship with nonulcer
      dyspepsia. H pylori infection is currently diagnosed by either endoscopic biopsy
      or serologic titers for a specific immunoglobulin (IgG) antibody. No noninvasive
      technique is available to document eradication of infection, although urea breath
      tests will soon simplify both the diagnosis of infection and documentation of
      eradication. Eradicating H pylori infection decreases the rate of ulcer
      recurrence. Treatment currently involves a 2-week, three-drug regimen of bismuth
      subsalicylate, tetracycline, and metronidazole, or a two-drug regimen of
      omeprazole and amoxicillin; other, simpler regimens are under investigation.

PMID- 7736635
TI  - Treatment of genital HPV-infections with natural alpha interferon from normal
      human leucocytes.
AB  - The antiviral action of Alpha Interferon is much more important than
      antiproliferous and immunomodulating actions. In any case, all of them are
      required to resolve pre-neoplastic pathologies of the female genital tract,
      especially if they are at an initial stage or associated with virus cytopathic
      effects.

PMID- 7736636
TI  - The role of endovaginal ultrasound in differentiating endometriomas from other
      ovarian cysts.
AB  - Endometriomas have a prevalence of 24% among all ovarian cysts. Various
      sonographic features have been proposed to identify endometriomas. Although the
      visualization of ovarian masses with low-level internal echoes is suggestive for
      the endometriotic origin of the cyst, no data are yet available on the
      specificity of endovaginal ultrasonography in differentiating endometriomas from
      other ovarian masses. To address this issue, the sensitivity, specificity,
      negative and positive predictive values of endovaginal ultrasonography in
      comparison with pathology were calculated for each visualized cyst. The study
      population (n = 251) consisted of all premenopausal non pregnant women submitted
      to laparotomy or laparoscopy between May 1991 and March 1993 at the Department of
      Obstetrics and Gynecology of the University of Cagliari. Within one week before
      surgery, all patients underwent endovaginal ultrasonography and 93 ovarian cysts
      were visualized. After the scan, the physician gave prospective impressions as to
      the presence of endometriomas using the visualization of round-shaped homogeneous
      hypoechoic "tissue" of low-level echoes within the ovary as characteristic
      ultrasonographic finding. Ultrasonographic impression was compared with
      histopathological diagnosis. Out of 93 adnexal masses detected by ultrasound, 31
      were suspected to be endometriomas and the diagnosis was confirmed in 24. The
      sensitivity and the specificity of endovaginal ultrasonography in differentiating
      endometriomas from other ovarian cysts were 83% and 89%, respectively. This
      specificity (89%) is comparable with that obtainable with magnetic resonance
      imaging (91%).

PMID- 7736637
TI  - Hysteroscopic tubal catheterization in diagnosis and treatment of proximal
      oviductal obstruction.
AB  - Hysteroscopic tubal catheterization in patients with proximal tube obstruction,
      was successful in our material in 11 out of 15 cases. In 36.6% women this
      pathology was connected to the presence of pathologic microflora in the oviducts,
      as confirmed by bacteriological examination of tubal fluid. The pregnancy rate in
      endoscopically treated patients reached 13.3%. Three months follow-up HSG showed
      that in 78% of cases insertion of a catheter into their oviducts resulted in
      their complete patency. Hysteroscopic tubal catheterization failed in 4 women,
      who were subsequently qualified to IVF. The present study shows that
      hysteroscopic tubal catheterization in patients with proximal tubal obstruction
      can be used both as a diagnostic and considerably effective therapeutic method.

PMID- 7736638
TI  - The effect of gestanone and ethynyl estradiol on benign breast disease.
AB  - The evidence related to the effects of Ocs on the breast benign diseases and
      their secondary relation to malignancy is studied. Our data are in concordance
      with other epidemiological studies, that showed no influence on breast mitosis
      and apoptosis and that there was a reduced incidence of benign breast disease; we
      also believe that it has a beneficial effect and that this method of
      contraception is the best.

PMID- 7736639
TI  - An Italian survey on how information campaigns about AIDS have changed
      contraception in young couples. A sectional study and a comparison with the
      literature.
AB  - The purpose of the present investigation was to ascertain whether adolescent had
      been sensitized by the campaign against AIDS and if their behaviour regarding the
      use of contraception had changed accordingly. To this end 2,000 questionnaires
      (of which 1,554 were returned) were distributed to a population aged 13-20 years,
      recruited from high schools or sporting centers. The results of our survey, which
      started in 1992 and lasted 15 months, indicate that after the informative
      campaigns of 1986, contraceptive habits have changed, and at present, the method
      predominantly used by teenagers (60.6%) at their first sexual intercourse is the
      condom. The results of the present study have been compared with those of the
      literature regarding the years previous to our study. In our investigation, only
      18.9% of the interviewed used oral contraception vs. 43.3% and 34.50% of those
      reported in 1980-85 and 1986-89, respectively. Particularly significant is the
      fact that 11.6% of teenagers used the condom in addition to oral contraception at
      their first sexual intercourse. In conclusion, we can assert that AIDS campaigns
      conducted in Italy, starting from 1986, has resulted in an increase of the use of
      condoms with respect to other methods of contraception.

PMID- 7736640
TI  - Epidemiological aspects of vaginal intraepithelial neoplasia (VAIN).
AB  - In order to evaluate the natural history of Vaginal Intraepithelial Neoplasia
      (VAIN), its epidemiological characteristics and the risk of its evolving into
      Invasive Carcinoma, we studied direct vaginal biopsies from 376 outpatients, we
      ascertained the predominant disease site and investigated whether the lesions
      (uni or multicentric) were only vaginal, were present at both the cervix and the
      vagina or were an extension of cervical lesions (DES-like areas). Moreover, in
      cervical and vaginal biopsies from 265 patients, we compared the severity of
      intraepithelial neoplasia of the vagina and cervix. In our series, vaginal
      lesions accounted for over half (52.6%) of the alterations attributable to HPV
      infection, while VAIN accounted for 46.5%; in 84.8% of cases, VAIN was associated
      with HPV. In 49.8% of cases, biopsies were from the upper third of the vagina and
      in 74.8% the pathological areas involved both the cervix and the vagina. The DES
      like zone accounted for 7.9% of cases, vaginal wall involvement being limited to
      the upper third. Finally, the comparison of histological findings, in the 265
      patients, confirmed that in 69.8% cases vaginal and cervical lesions were of the
      same grade; in 18.8% vaginal lesions were more severe than cervical lesions. In
      our study a higher number of vaginal biopsies were taken than in previous years,
      and it is difficult to establish whether this depends on improved diagnostic
      methods or on changes in epithemiological factors, such as the reported increase
      in the incidence of HPV lesions. A systemic search for lesions and a study on
      their evolution are therefore required to clarify this aspect.

PMID- 7736641
TI  - The role of beta-endorphin in pregnancy and delivery.
AB  - This paper deals with beta-endorphin determination in 20 autopsy specimens of
      human fetal and neonatal pancreas, as well as in the placental tissue specimens
      of the same fetoplacental units, by means of radioimmunoassay (RIA-Nichols
      Institute). Peripheral blood samples of 10 healthy non-gravids were taken as
      controls. Our results present a marked increase of beta-endorphin levels with the
      progression of gestation, reaching a peak of 3960 pg/g at term. The data obtained
      indicate that beta-endorphin plays an important role in pregnancy and delivery
      regulation.

PMID- 7736642
TI  - Hysteroscopic follow-up in tamoxifen treatment for breast cancer.
AB  - In the postmenopausal women endocrinotherapy proves to be as useful as the
      cytotoxic treatment in breast cancer therapy, regarding the percentage and
      duration of response, both in prophylactic and palliative therapy, with the
      advantage of milder side-effects and a better quality of life. This study was
      carried out in order to evaluate the Tamoxifen weak estrogenic activity, which
      could appear during long-term therapies, determining endometrial morphological
      modifications. Twenty-one postmenopausal women suffering from breast cancer
      underwent hysteroscopy with target biopsy or curettage at the same time with
      mastectomy and afterwards during additional Tamoxifen treatment at 12 and 24
      months. Our results confirm that this simple, outpatient endoscopic investigation
      should be provided as a routine in the follow-up of oncologic patients during
      hormonotherapy.

PMID- 7736643
TI  - Clinical and pathological evaluation of large loop diathermy excision of the
      transformation zone.
AB  - In order to make accurate diagnosis and to carry out treatment of cervical
      preneoplastic disease, large loop diathermy excision of the transformation zone
      was performed in 98 patients. The colposcopic assessment was indicated by
      abnormal smear or history of treatment for preneoplastic changes. The entire
      transformation zone could be excised in one piece in 90% of cases. Histological
      examination of the specimens confirmed dysplasia in 89% of patients and in 4
      cases invasive cervical disease was revealed. The ectocervical and endocervical
      excision margins were free of dysplastic epithelium in 68% of cases. Compared to
      traditional cone biopsy, the new method is cheaper and more simple. Loop
      diathermy excision of the transformation zone can be performed in local
      anaesthesia as an out-patient procedure and there is no need for postoperative
      hospitalization. By reducing the number of general anesthesia, the workload in
      gynaecological theatres and by eliminating the need for postoperative hospital
      stay the method substantially contributes to the improvement of the hospital
      budget.

PMID- 7736644
TI  - Vulvo-vaginitis and reproduction.
AB  - The main micro-organisms able to interfere with the reproductive function have
      been considered. In particular, the problems concerning the vaginal environment
      and its interactions with spermatozoa, immunological aspects and contraception.
      Lastly, reference has been made to methods of prevention and study in the field
      of diagnostics and of clinical management.

PMID- 7736645
TI  - Biogenetic amines in placental tissue. Relation to the contractile activity of
      the human uterus. Preliminary communication.
AB  - OBJECT: To examine the distribution of mast cells in human placental tissue and
      to analyse the interactions between mast cell mediators (histamine and serotonin
      (5-HT)) and contractile activity of the uterus during delivery. DESIGN: 34
      placentas were examined. Histamine and serotonin levels in placental samples were
      estimated using fluorymetric method. Distribution of mast cells were analysed
      immunohistochemically on the same material. SETTING: Dept. of Pathophysiology,
      Medical Academy, Warsaw, Poland. (*) Laboratory of Developmental Neuropathology
      Centre of Experimental and Clinical Medicine, Polish Academy of Sciences, Warsaw.
      (**) Clinic of Obstetrics and Gynecology, Second Medical Faculty, Medical
      Academy, Warsaw. SUBJECTS: 34 women, whose pregnancies ended in time and in
      preterm delivery, with normal, abnormal or without contractile activity of the
      uterus (elective cesarean section). MAIN OUTCOME MEASUREMENTS: Comparative charts
      of histamine levels in placental samples in relation to term and course of the
      labour. RESULTS: Concentration of histamine in placental cuts obtained from
      maternal surface of the placenta was significantly higher in the case of delivery
      without contractile activity of the uterus (elective cesarean section).
      Immunohistochemical identification of mast cells proved, that in regions located
      close to fetal surface of the placenta and in connective tissue foci, mast cells
      were most numerous. CONCLUSIONS: It is postulated that the simultaneous release
      of mast cell mediators (especially histamine) in placental tissue could be an
      important factor for evoking contractile activity of the human uterus, initiating
      labour. Further investigations should give answers on the points of these
      dependences.

PMID- 7736646
TI  - Risk factors for complicating infections after cesarean section.
AB  - In this study of 906 women who underwent Cesarean Section without the use of an
      antibiotic prophylactic it has been confirmed that age, labour in course and the
      premature rupture of the membrane are clinical parameters that are statistically
      significant for unspecified fever/endometritis or for infections of the wound and
      that hemoglobin and hematocrit values below 9 gr/dl and at 35% post-operation are
      significant for infections of the wound. 13.2% women had complicating infections
      of which 1.3% were infections of the wound, 0.6% were endometritis, 7.2% were
      unspecified fever and 4.1% were urinary infections. The Authors show that
      preventive measures in some areas could be as effective as chemoprophylaxis.

PMID- 7736647
TI  - Effects of neutrophil chemotactic factors on cervical ripening.
AB  - Our aim was to study the effects of infection mediated by bacterial endotoxins
      (lipopolysaccharides LPS) and bacterial substrate (N-formyl-methionyl-leucyl
      phenylalanine FMLP) on pathological cervical ripening, and compare their effects
      with the normal physiological mediator interleukin-8 (IL-8). Twenty non-pregnant
      rabbits were treated vaginally either by placebo, LPS, FMLP or IL-8 for 3
      successive days. Water concentration was measured. Neutrophils were counted in 5
      random fields of each specimen. Collagen and glycosaminoglycan concentrations
      were assessed histologically by using picrosirius red and alcian blue staining
      and optical density was calculated. LPS FMLP as well as IL-8 can induce cervical
      ripening. Water concentration was found to be significantly increased in these
      groups (p < 0.0001). Also, significant numbers of neutrophils were found to
      accumulate in the connective tissue of these cervices (p < 0.0001). Collagen
      concentration was significantly decreased in the cervices treated by LPS, FMLP
      and IL-8 (p < 0.0001). Glycosaminoglycan concentration was significantly
      increased in cervices treated by LPS, FMLI as well as IL-8 (p < 0.0001, 0.006 and
      0.001 respectively). LPS, FMLP and IL-8 stimulate cervical ripening in non
      pregnant rabbits. This ripening was mediated through the accumulated neutrophils
      in the connective tissue. IL-8 has a physiological type effect to induce ripening
      of the cervix.

PMID- 7736648
TI  - The Mayer-von Rokitansky-Kuster-Hauser syndrome (uterus bipartitus solidus
      rudimentarius cum vagina solida): the development of gynecology through the
      history of a name.
AB  - A summary of the original descriptions of the Authors who gave the name to the
      syndrome characterized by absence of uterus and vagina is presented. Through
      these original descriptions a complete view of the development in gynecology over
      the last 150 years is offered.

PMID- 7736649
TI  - Pure FSH (Metrodin) for ovarian stimulation in the IVF-ET programme.
AB  - PURPOSE: a comparative analysis of the clinical effectiveness of pure FSH
      (Metrodin) and conventional gonadotropin (Pergonal) for ovarian stimulation was
      performed. METHODS: each group consisted of 30 selected patients with tubal
      infertility, practically identical by average age, duration of infertility, age
      at menarche, weight and height and husband's semen analysis. The average number
      of vials of drug used for stimulation, number of oocytes retrieved and embryos
      transferred was the same for both groups of patients. The failure of oocyte
      retrieval and fertilization was higher in the Pergonal (16.8%) than in the
      Metrodin group (6.8%). RESULTS: in both groups there were 8 pregnancies--4 in the
      Pergonal and 4 in Metrodin group. All pregnancies in the pure FSH group resulted
      in the delivery of a healthy baby, while in the Pergonal group there were two
      deliveries and two spontaneous abortions. AUTHOR'S CONCLUSIONS: evaluating the
      data we can conclude that pure FSH stimulation provides respectively lower
      failure and spontaneous abortion rates than Pergonal stimulation, leading to a
      higher take home baby rate.

PMID- 7736650
TI  - Contrasting effects of isoproterenol and phosphodiesterase III inhibitor on
      intracellular calcium transients in cardiac myocytes from failing hearts.
AB  - 1. Effects of a newly developed phosphodiesterase (PDE) III inhibitor, E-1020, on
      intracellular calcium transients were compared with those of isoproterenol (ISO)
      in isolated single myocytes from failing hearts secondary to pulmonary
      hypertension induced by monocrotaline injection. Myocytes were isolated by enzyme
      digestion using a Langendorff apparatus. Changes in intracellular calcium
      concentrations ([Ca2+]i) were recorded using a fura-2 fluorescence microscopic
      technique. Cyclic AMP contents of the hearts were measured by radio-immunoassay.
      2. Myocytes from failing hearts showed Ca2+ transients with a low peak (low
      amplitude) and delayed decline of Ca2+ transients. Both ISO and E-1020 increased
      peak [Ca2+]i, max + d[Ca2+]i/dt, and max - d[Ca2+]i/dt in a concentration
      dependent manner while both agents decreased T80L (time to 80% decline of
      amplitude from peak light). The concentrations which increased peak [Ca2+]i by
      50% were 1.6 x 10(-9) mol/L of ISO and 2 x 10(-6) mol/L of E-1020. These
      concentrations increased cAMP in the heart to the same levels. Analysis of the
      effects of both agents on peak [Ca2+]i versus max - d[Ca2+]i/dt showed that ISO
      is much more effective on peak [Ca2+]i while E-1020 is more effective on max -
      d[Ca2+]i/dt. 3. These results showed that the effects of ISO and E-1020 on the
      parameters of intracellular Ca2+ transients of single myocytes from failing
      hearts are slightly different, and suggest that E-1020 may improve diastolic
      function as well as systolic function in failing hearts.

PMID- 7736651
TI  - Calcium transients in single myocytes and membranous ultrastructures during the
      development of cardiac hypertrophy and heart failure in rats.
AB  - 1. We examined changes in intracellular calcium transients of separated single
      myocytes from the right ventricle (RV) of the rat heart during the change from
      adaptation to maladaptation in response to a pressure overload. 2. Right
      ventricular hypertrophy (RVH) secondary to pulmonary hypertension was induced by
      a subcutaneous injection of monocrotaline. Developed tensions of the RV-free wall
      were decreased as RVH progressed. Single myocytes were separated from the RV
      during different stages of RVH. Fura-2/AM-loaded cells were field stimulated, and
      changes in calcium transients were measured by Olympus OSP-3 system. We also
      examined membranous ultrastructures (sarcoplasmic reticulum, mitochondria,
      surface caveolae) involved in calcium metabolism in the hearts using scanning
      electron microscopy. 3. We observed characteristic changes in calcium transients
      during the change from adaptation to maladaptation, and also found that one
      parameter (amplitude) of calcium transients appeared to be correlated with the
      changes in the number of sarcoplasmic reticulum. 4. These results provided some
      insights into the mechanism of calcium handling of hypertrophied heart in
      response to a pressure overload from adaptation to maladaptation especially when
      stimulatory frequency was high, and suggested that heart rate control is a very
      important factor for the treatment of patients with congestive heart failure.

PMID- 7736652
TI  - ANTISENSE oligonucleotides: a new tool in neuroscience.
AB  - 1. Recent studies have shown that gene expression can be selectively attenuated
      by administration of short sequences of nucleotides (oligonucleotides) that are
      complementary to a portion of messenger RNA coding for a particular gene product.
      2. This technique is known as ANTISENSE, because the oligonucleotides are
      complementary to the mRNA which has the same sequence as the SENSE strand of DNA.
      3. In the present review we focus, after a brief discussion of gene expression
      and mechanisms of action of ANTISENSE, on the methodological aspects of ANTISENSE
      experiments in neuroscience. In particular, we address the advantages,
      disadvantages and controls for the ANTISENSE technique, as well as the choice,
      design, mode of delivery, dose and storage of ANTISENSE oligonucleotides.

PMID- 7736653
TI  - Pharmacological properties of the natural marine product furospongin-1.
AB  - 1. The natural marine product, furospongin-1 (6, 12 and 24.5 mumol/L)
      significantly inhibited contractions of segments of guinea-pig ileum induced by
      submaximal concentrations (0.1 mumol/L) of acetylcholine (ACh) and histamine.
      Furospongin-1 (24.5 and 36.7 mumol/L) reduced both the phasic and tonic
      components of a contraction induced by 30 mumol/L K+ solution in the absence and
      presence of atropine (1 mumol/L), mepyramine (1 mumol/L) and phentolamine (1
      mumol/L). Furospongin-1 also decreased basal tension and the amplitude of
      spontaneous phasic contractions of guinea-pig ileum. 2. The mitochondrial ATP
      synthase inhibitor oligomycin (0.3, 1 and 3 mumol/L) had a similar concentration
      dependent action, reducing basal activity and contractions evoked by histamine
      and ACh. Oligomycin also reduced both the phasic and tonic components of a
      contraction induced by 30 mmol/L K+ solution in the absence and presence of
      atropine (1 mumol/L), mepyramine (1 mumol/L) and phentolamine (1 mumol/L). 3.
      Furospongin-1 (6 and 37.6 mumol/L) and oligomycin (3 mumol/L) had no effect on
      contractions of chemically skinned guinea-pig ileum longitudinal muscle segments.
      In this same tissue, furospongin-1 (6, 12 and 24.5 mumol/L) and oligomycin (0.3,
      1 and 3 mumol/L) concentration-dependently reduced tissue levels of ATP. 4. In
      lyzed bovine mitochondria, oligomycin (0.1, 0.3, 1 and 3 mumol/L) inhibited
      conversion of ATP to ADP whilst furospongin-1 (6, 12 and 24.5 mumol/L) and
      carbonyl cyanide m-chlorophenylhydrazone (0.5 mmol/L) had no significant effect
      on ATP breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736654
TI  - Influence of alpha 1-adrenoceptor antagonism of ketanserin on the nature of its 5
      HT2 receptor antagonism.
AB  - 1. In order to investigate alpha 1-adrenoceptor interactions with 5-HT2
      receptors, the effect of ketanserin (which antagonizes both types of the above
      receptors) on responses to 5-hydroxytryptamine (5-HT) and phenylephrine (PE) was
      measured in isolated perfused rat tail arteries. 2. Ketanserin was found to be a
      competitive antagonist at 5-HT2 receptors (pA2 = 9.19) and alpha 1-adrenoceptors
      (pA2 = 7.52). 3. Ritanserin, an analogue of ketanserin with very weak alpha 1
      adrenoceptor antagonist activity, was found to be a potent non-competitive 5-HT2
      receptor antagonist. 4. In the presence of the potent alpha 1-adrenoceptor
      antagonist prazosin, ketanserin was a non-competitive 5-HT2 receptor antagonist.
      5. Thus, for ketanserin to exhibit competitive 5-HT2 receptor antagonism, its
      coexisting alpha 1-adrenoceptor antagonist property appears mandatory.

PMID- 7736655
TI  - Differences in endothelium-dependent relaxation in various arteries from Watanabe
      heritable hyperlipidaemic rabbits with increasing age.
AB  - 1. Endothelium-dependent relaxation in response to acetylcholine (ACh) and the
      calcium ionophore A23187 was examined in aorta, coronary, basilar and renal
      arteries isolated from Watanabe heritable hyperlipidaemic (WHHL) rabbits of 2, 6
      and 12 months of age, with normolipidaemic heterozygous WHHL rabbits as controls.
      2. In the rings of WHHL rabbit aortae and coronary arteries preconstricted with
      vasoconstrictors, endothelium-dependent relaxation in response to ACh was
      attenuated with age compared to the heterozygous WHHL rabbits. A significant
      negative correlation was found between the total cholesterol content and the
      relaxation response to ACh in the aortae or coronary arteries from 6 and 12 month
      old WHHL rabbits. 3. In the rings of basilar arteries, endothelium-dependent
      relaxations to ACh were not modified with age. Similarly, in the rings of renal
      arteries, the relaxation response to ACh was not changed with age, but in the 6
      and 12 month preparations, after the age of 6 months, a contraction following the
      relaxation appeared at higher concentrations of ACh (10(-7) to 10(-6) mol/L). The
      contraction was endothelium-dependent and inhibited by indomethacin. 4. A23187
      induced endothelium-dependent relaxations were also markedly attenuated in the
      aorta and significantly in the coronary artery with age. 5. Endothelium
      independent relaxation to sodium nitroprusside was not changed in all arteries
      from WHHL rabbits of different ages. 6. These findings indicate that in the aorta
      and coronary artery of the WHHL rabbit, the endothelium-dependent relaxation to
      ACh and A23187 becomes impaired with increasing age (i.e., with the progression
      of cholesterol deposition in the arterial wall) but is preserved in the basilar
      and renal artery.

PMID- 7736656
TI  - Effects of prolonged (48 h) infusion of cortisol on blood pressure, renal
      function and fetal fluids in the immature ovine foetus.
AB  - 1. This study describes the effects of prolonged (48 h) infusion of cortisol into
      ovine foetuses (100-110 days of gestation: term is 150 days) at a time when
      endogenous plasma cortisol concentrations are < 5 nmol/L. 2. In four chronically
      cannulated foetuses (107 +/- 0.9 day) the infusion of saline (0.9% NaCl; w:v 0.19
      mL/h, 48 h) had no effect on blood pressure, renal function, or composition of
      amniotic and allantoic fluids. 3. In six foetuses (107 +/- 1 day) the infusion of
      cortisol (250 micrograms/h) increased plasma cortisol concentrations from 4.1 +/-
      0.7 to 118 +/- 9 nmol/L (P < 0.001), increased mean arterial pressure from 34 +/-
      1 to 40 +/- 1 mmHg (P < 0.001), increased glomerular filtration rate (P < 0.05),
      urine flow rate, and free water clearance (P < 0.01). 4. There was a significant
      increase in excretion rates of potassium and creatinine as a result of cortisol
      infusion, but no natriuresis, indicating some functional maturation of the fetal
      kidney. 5. Cortisol infusion had no effect on the volumes of amniotic and
      allantoic fluids; allantoic fluid composition was unchanged; significant
      decreases occurred in amniotic fluid osmolality, sodium and chloride
      concentrations, and in lung liquid osmolality, potassium, creatinine, magnesium,
      glucose and fructose concentrations. 6. Thus prolonged exposure of the immature
      ovine foetus to elevated cortisol concentrations produced significant alterations
      in the water and electrolyte balance of the foetus.

PMID- 7736657
TI  - Hyperproliferation of aortic smooth muscle cells and fibroblasts from young SHR
      rats is not shared by endothelial cells.
AB  - 1. To study the hypertensive genotypic influence on growth kinetics of the three
      aortic wall cell types. 2. Using young spontaneously hypertensive (SHR) and
      Wistar-Kyoto (WKY) rats weighing 160-180 g, we compared the proliferative
      properties of endothelial cells (EC), smooth muscle cells (SMC) and fibroblasts
      that were isolated from the thoracic aorta of each strain and cultured. Growth
      arrested cells were exposed to P < -thymidine after stimulation with 150
      micrograms/mL endothelial cell growth supplement. Proliferation assays were
      performed by cell seeding on decellularized aortic explants and cell counting 2,
      4, 5, 6 and 7 days after seeding. The influence of SMC from SHR on the growth
      kinetics of EC was evaluated by co-cultures in transwell systems. 3. After
      stimulation, SMC from SHR exhibited a greater P < -thymidine incorporation rate
      than those from WKY rats (ratios over controls: 3.90 +/- 0.48 [7] vs 1.85 +/-
      0.25 [7] respectively, P < 0.05). This was also true for adventitial SHR
      fibroblasts: (13.1 +/- 0.6 [6] vs 9.9 +/- 1.0 [6] WKY P < 0.05). On the contrary,
      there was no difference in the P < -thymidine incorporation rates between EC of
      each strain, regardless of the passage and the time considered. Cell
      proliferation on matrix explants confirmed the hyperproliferation of SMC and
      fibroblasts from SHR, while EC of each strain proliferated equally. Smooth muscle
      cells from SHR did not influence the growth kinetics of EC in co-culture and vice
      versa. 4. The changes in growth patterns of aortic cells isolated from young
      prehypertensive SHR seem to be restricted to SMC and fibroblasts.

PMID- 7736658
TI  - Involvement of transforming growth factor-beta 1 for platelets-induced
      stimulation of endothelin-1 production.
AB  - 1. Possible mechanisms by which platelets stimulate the production of endothelin
      1 (ET-1) in vascular endothelial cells (EC) were investigated. 2. A supernatant
      of platelets stimulated the expression of prepro ET-1 mRNA, followed by an
      increased secretion of ET-1 from cultured EC. These responses were markedly
      enhanced by pretreatment of the platelets with thrombin, at a concentration which
      did not influence the ET-1 production in EC. A platelet suspension, separated
      from cultured EC by a permeable nylon membrane, also markedly stimulated the ET-1
      secretion from EC. 3. Endothelin-1 production enhanced by the platelet
      supernatant, with or without thrombin pretreatment, correlated with the active
      transforming growth factor-beta 1 (TGF-beta 1) concentrations in the supernatant.
      The supernatant-induced increase in ET-1 secretion from the EC was markedly
      suppressed by TGF-beta 1 neutralizing antibody. 4. We tentatively conclude that
      platelets stimulate the endothelial ET-1 production by releasing a bioactive
      diffusible substance, mainly TGF-beta 1.

PMID- 7736659
TI  - Acute toxicity of bupivacaine metabolites in mice.
AB  - 1. This study was designed to document the acute toxicity of two metabolites of
      bupivacaine, desbutylbupivacaine (2,6, desbutylbupivacaine; PPX) and pipecolic
      acid in mice. All the compounds were administered by the intraperitoneal (i.p.)
      route. 2. The mean convulsant activity was 100% for controls, 30, 100, 100, 100
      and 90% for 400, 200, 150, 125 and 112.5 mg/kg i.p. of PPX, respectively, and 0%
      for the animals receiving pipecolic acid. 3. The acute induced mortality was 60%
      for bupivacaine control group (50 mg/kg/i.p.), 60, 30 and 0% for 800, 400 and 200
      mg/kg of pipecolic acid, respectively, and 100, 90, 60, 80 and 10% for 400, 200,
      150, 125 and 112.5 mg/kg i.p. of PPX, respectively. 4. The time to convulse was
      158 +/- 16 s for bupivacaine, 230 +/- 30, 270 +/- 24, 255 +/- 21, 442 +/- 84 and
      418 +/- 32 s for 200, 150, 125, 112.5 and 100 mg/kg i.p. of PPX, respectively;
      any pipecolic acid treated animal have convulsed. 5. In conclusion, the present
      study demonstrated that PPX is more toxic than expected since we found that its
      induced mortality was approximately three times that found for bupivacaine and
      its CNS toxicity was about two times that of bupivacaine.

PMID- 7736660
TI  - Germ cell-Sertoli cell interactions: regulation by germ cells of the stage
      specific expression of CP-2/cathepsin L mRNA by Sertoli cells.
AB  - CP-2/cathepsin L mRNA is expressed primarily by rat Sertoli cells within stage VI
      VIII seminiferous tubules. To test whether germ cells regulated this expression,
      we examined if separating Sertoli cells from specific germ cells affected
      expression of this transcript in Sertoli cells. First, Sertoli cells were
      isolated from adult (90-day-old) and immature (25-day-old) rats and levels of
      this transcript measured immediately or after 1, 3 and 5 days in culture. Results
      demonstrated that immediately upon isolation, CP-2/cathepsin L mRNA levels were
      significantly higher in mature cells. However, after 1 day in culture, the levels
      of this transcript increased in immature cells and remained high in mature cells.
      We therefore conclude that in vivo, a subset of germ cells inhibit the expression
      of CP-2/cathepsin L mRNA by immature Sertoli cells. Second, to examine the effect
      of specific germ cells on CP-2/cathepsin L mRNA expression, we exposed the testes
      of mature rats to 3 Gy of gamma-radiation and analyzed stage-specific expression
      of this transcript at varying times during maturation depletion and subsequent
      germ cell restoration. Loss of spermatogonia or spermatocytes was without effect.
      However, when pachytene spermatocytes through step 14 spermatids were depleted,
      expression at stages VI-VIII was reduced by half and expression at stages IX-I
      was increased 14-fold. These changes resulted in the loss of stage-specific
      expression of CP-2/cathepsin L mRNA by Sertoli cells. Finally, stage VI-VIII
      tubules, depleted primarily in step 15-19 spermatids, had levels of CP
      2/cathepsin L mRNA that were 60% of control. However, stage-specific expression
      of this transcript was detected in these tubules. In contrast to what we noted
      with CP-2/cathepsin L mRNA, loss and restoration of germ cells had no effect on
      Sertoli cell levels of SGP-2 mRNA, indicating that testicular irradiation had no
      overall effect on Sertoli cell function. Taken together, these data suggest that
      the stage-specific expression of the CP-2/cathepsin L gene results from the
      sequential stimulation and inhibition of Sertoli cells by germ cells, that
      pachytene spermatocytes through step 14 spermatids are required for this stage
      specific expression and that step 18 and 19 spermatids amplify this expression at
      stages VI-VIII.

PMID- 7736661
TI  - Transcriptional regulation of Sertoli cell differentiation (transferrin promoter
      activation) during testicular development.
AB  - Previously testicular peritubular cells have been shown to produce a paracrine
      factor PModS that promotes Sertoli cell differentiation. This mesenchymal
      epithelial cell interaction appears to regulate a number of Sertoli cell
      differentiated functions including transferrin gene expression. The current study
      was designed to identify PModS-activated response elements in the transferrin
      promoter and correlate this with Sertoli cell differentiation that occurs during
      testis development. The 3-kb transferrin promoter was digested down to
      approximately 200-bp fragments. Nuclear extracts from Sertoli cells stimulated
      with PModS were used in gel mobility shift assays. Two promoter regions located
      at -2.4 kb and -1.9 kb were designated SE1 and SE2. PModS promoted the presence
      of factors in Sertoli cell nuclear extracts that bind SE1 and SE2. Displacement
      studies demonstrated that SE1 and SE2 are distinct. A transferrin promoter
      reporter construct containing these apparent response elements was activated by
      PModS, while a minimal transferrin promoter by 600bp excluding SE1 and SE2 was
      only partially stimulated by PModS. Therefore, PModS appears to in part activate
      the transferrin promoter through SE1 and/or SE2. Gel shift assays with Sertoli
      cell nuclear extracts and 20-day-old testis extracts were the same.
      Interestingly, the nuclear extract from a newborn testis also had a gel shift.
      Therefore, some of the nuclear factors stimulated by PModS in Sertoli cells and
      present in mid-pubertal testis were also present at birth upon completion of
      embryonic development. Previously transferrin expression has been shown to
      increase significantly at the onset of puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736662
TI  - A haploid and a diploid cell coexist in an in vitro immortalized spermatogenic
      cell line.
AB  - We have recently established a conditionally immortalized germ cell line [GC
      2spd(ts)] that, at the permissive temperatures of 37 degrees C and 32 degrees C,
      is able to undergo meiosis in vitro and form round spermatids [Hofmann et al.,
      (1994): Proc Natl Acad Sci USA 91:5533-5537]. In this report, we provide data
      that indicate that the GC-2spd(ts) cell line consists of two cell populations
      undergoing a haploid (n/2n) cell cycle and a diploid (2n/4n) cell cycle,
      respectively. The cells containing 2n DNA, when sorted by fluorescence-activated
      cell sorting, are able to reconstitute the full population of n/2n/4n DNA cells,
      indicating that they are able to commit to the reductive meiotic division and
      form haploid spermatids or to continue self-replication through a diploid cell
      cycle. This GC-2spd(ts) cell line provides a valuable tool to study the molecular
      mechanisms involved in the cellular decision between self-renewal by mitosis and
      commitment to meiosis.

PMID- 7736663
TI  - Culture of pachytene spermatocytes for analysis of meiosis.
AB  - An impediment to the investigation of mammalian spermatogenic meiosis has been
      the lack of an appropriate system for experimental manipulation of meiotic
      prophase cells. We report here the use of a simple system for the short-term
      culture of pachytene spermatocytes. We have assayed parameters of cell function
      pertinent to meiotic prophase, namely chromosome pairing and synapsis. During the
      culture period of 24-48 hr, cells maintained typical pachytene morphology,
      chromatin condensation patterns, and chromosome pairing, as assessed by light and
      electron microscopy. Uridine incorporation, monitored by autoradiography,
      reflected the chromosomal distribution found in vivo in that the autosomal
      chromosomes were transcriptionally active, while the sex chromosomes were not.
      Thus features of chromosome pairing and sex chromatin inactivation are maintained
      in these cultures. We have conducted experiments to demonstrate that cultured
      pachytene spermatocytes can be useful for the analysis of agents, some of which
      may be suspected mutagens, that might affect chromosome structure and function
      during meiosis. Treatment of cells with actinomycin D revealed a differential
      effect on chromatin condensation in the autosomes versus the sex chromosomes.
      Camptothecin, a topoisomerase inhibitor, induced desynapsis of paired
      chromosomes. Okadaic acid, a phosphatase inhibitor, induced premature metaphase-I
      condensation of pachytene chromosomes. This last experiment suggests that these
      cultured cells may be useful for analysis of meiotic cell cycle controls. Taken
      together, these results demonstrate a culture system that can be useful for
      analysis of meiotic events as well as in screening for potential mutagenic agents
      that might affect meiotic chromosome structure and function.

PMID- 7736664
TI  - Biochemical analysis of programmed cell death during premeiotic stages of
      spermatogenesis in vivo and in vitro.
AB  - Control points of regulator action during spermatogenesis are not completely
      known. Using the shark testis model, which facilitates analysis of
      spermatogenesis stage-by-stage in vivo and in vitro, an early biochemical marker
      of programmed cell death (PCD) was detected. Nucleosomal oligomers were seen in
      DNA extracts of testis and isolated spermatocysts (clonal germ cell/Sertoli cell
      units) at premeiotic (PrM), but not meiotic (M) or postmeiotic (PoM), stages.
      Cell nuclei isolated from M stages of development were susceptible to cleavage by
      micrococcal nuclease, suggesting that developmental control of factors other than
      a nuclease-insensitive chromatin structure may account for stage specificity.
      Cytological features of apoptosis were seen in germ cells, but not Sertoli cells,
      of a subset of isolated PrM spermatocysts and appeared to be all-or-none in
      affected clones. In culture, DNA fragmentation occurred on schedule with or
      without various additives, but the phosphodiesterase inhibitor 3-isobutyl-1
      methylxanthine (IBMX) decreased accumulation of DNA breakdown products.
      Identification of the apoptotic form of PCD as a major, variable component of
      normal spermatogenesis and the use of PrM spermatocysts as an in vitro test
      system will allow further definition of mechanisms and developmental and
      physiological controls.

PMID- 7736665
TI  - Regulation of beta-tubulin function and expression in Drosophila spermatogenesis.
AB  - In this study we examined two aspects of beta-tubulin function in Drosophila
      spermatogenesis: 1) beta-tubulin structural requirements for assembly of
      different categories of microtubules and 2) regulatory requirements for
      production of the correct tubulin protein level. In normal Drosophila
      spermatogenesis, the testis-specific beta 2-tubulin isoform supports multiple
      microtubule functions. Our previous work showed that another Drosophila isoform,
      beta 3, cannot support spermatogenesis, whereas a carboxyl-truncated form of beta
      2, beta 2 delta C, can at least to some extent provide all of beta 2's normal
      functions, save one: beta 2 delta C cannot support organization of axonemal
      microtubules into the supramolecular architecture of the axoneme. Here, to test
      whether beta 2 carboxyl sequences can rescue the functional failure of the beta 3
      isoform in spermatogenesis, we constructed a gene encoding a chimeric protein,
      beta 3 beta 2C, in which beta 3 sequences in the carboxyl region are replaced
      with those of beta 2. Unlike either beta 3 or beta 2 delta C, beta 3 beta 2C can
      provide partial function for both assembly of axonemal microtubules and their
      organization into the supramolecular architecture of the axoneme. In particular,
      the beta 2 carboxyl sequences mediate morphogenesis of the axoneme doublet tubule
      complex, including accessory microtubule assembly and attachment of spokes and
      linkers. However, our data also reveal aspects of beta 2-specific function that
      require structural features other than the primary sequence of the isotype
      defining variable regions, the C terminus and the internal variable region. Tests
      of fecundity in males that coexpress beta 2 and the chimeric beta 3 beta 2C
      protein showed that in Drosophila there are differential requirements for sperm
      motility in the male and in the female reproductive tract. Since some aspects of
      microtubule function in spermatogenesis are sensitive to the tubulin pool size,
      we examined the mechanisms for control of tubulin protein levels in the male germ
      cells. We found that both beta 2-tubulin mRNA accumulation and protein synthesis
      are dependent on gene dose, and that the level of expression is regulated by 3'
      noncoding sequences in the beta 2 gene. Our data show that the regulatory
      mechanisms that control tubulin pool levels in the Drosophila male germ line
      differ from those observed in cultured animal somatic cells. Finally, expression
      of transgenic constructs is consistent with early cessation of X chromosome
      expression in Drosophila spermatogenesis.

PMID- 7736666
TI  - Genomic organization of a mouse glyceraldehyde 3-phosphate dehydrogenase gene
      (Gapd-s) expressed in post-meiotic spermatogenic cells.
AB  - The Gapd-s gene encodes an isoform of the glyceraldehyde 3-phosphate
      dehydrogenase enzyme expressed only in post-meiotic spermatogenic cells. Two
      clones containing the Gapd-s gene were isolated from a mouse genomic library.
      Sequencing and restriction enzyme analysis demonstrated that this single-copy
      gene contains 11 exons and spans 9596 base pairs. The locations of Gapd-s exons
      and introns are conserved when compared to the corresponding portions of the
      chicken and human somatic Gapd genes. The promoter region contains no TATA box,
      although there is a potential SP1 recognition site within exon 1. Like other TATA
      less genes, primer extension analysis reveals some heterogeneity in the site of
      transcription initiation with Gapd-s transcripts initiating from three discrete
      sites. Northern analysis demonstrated that a 1.5-kb Gapd-s mRNA is expressed in
      the testis in at least three mammalian orders, indicating that the Gapd-s gene
      appeared early in mammalian evolution. Using GAPD-deficient bacteria, mouse GAPD
      S was shown to be capable of functioning as a glycolytic enzyme. Since GAPD has
      been proposed to be a key enzyme regulating glycolysis in spermatogenic cells,
      GAPD-S may represent a potential target for toxicological or contraceptive agents
      affecting fertility by interfering with glycolysis.

PMID- 7736667
TI  - Cell interactions in testis development: overexpression of c-mos in spermatocytes
      leads to increased germ cell proliferation.
AB  - Possible functions of the c-mos proto-oncogene during spermatogenesis were
      investigated through perturbations of its expression in transgenic mice. Two
      promoters, one from the pre-meiotic male germ cell-specific mouse
      phosphoglycerate kinase 2 gene, and the other from the post-meiotic male germ
      cell-specific rat RT7 gene were used to direct expression of c-mos. Northern blot
      analysis of testis RNA from transgenic PGK-c-mos mice indicated elevated levels
      of c-mos RNA in spermatocytes and spermatids compared to controls. No transgene
      expression was detected in any other tissue examined, suggesting that the mouse
      PGK2 promoter, like the previously used human PGK2 promoter, confers correct cell
      specific expression onto c-mos. The promoter from a newly characterized rat gene,
      RT7, was shown to direct expression specific to post-meiotic spermatids.
      Transgenic mice carrying an RT7-lacZ construct displayed immunoreactive bacterial
      beta-galactosidase as well as enzyme activity in round spermatids. The cellular
      specificity for beta-galactosidase expression observed in RT7-lacZ transgenic
      animals was in agreement with endogenous RT7 transcript expression. Northern blot
      analysis of testis RNA of RT7-c-mos transgenic mice showed elevated levels of c
      mos in spermatids, but not in other cells or tissues examined. Western blot
      analysis demonstrated elevated levels of p43c-mos in spermatids of both PGK-c-mos
      and RT7-c-mos transgenic animals, but only PGK-c-mos transgenics had increased
      p43c-mos levels in spermatocytes. Both RT7-c-mos and PGK-c-mos transgenic mice
      are fertile and show no tendency toward transformation. RT7-c-mos mice have no
      discernible phenotype associated with the c-mos overexpression in spermatids.
      However, PGK-c-mos transgenic males exhibited a significant increase in germ cell
      number, as determined by cell counts using total germ cells and germ cells
      fractionated by centrifugal elutriation. Because mitotic divisions of germ cells
      occur prior to PGK-c-mos transgene expression, our observations suggest that c
      mos overexpression in spermatocytes causes an alteration in cell-cell
      interactions.

PMID- 7736668
TI  - Identification of two positive transcriptional elements within the 91-base pair
      promoter for mouse testis angiotensin converting enzyme (testis ACE).
AB  - Testis angiotensin-converting enzyme (testis ACE) is an isozyme of ACE only
      expressed by male germ cells during spermiogenesis. It is the result of a strong
      sperm-specific promoter found within the 12th intron of the somatic ACE gene.
      Previous studies have localized the boundaries of the mouse testis ACE promoter
      as being from -91 to -9, relative to the transcriptional start site, and have
      suggested two important DNA regulatory elements starting at positions -55 and 
      32. DNA constructs were made in which these motifs were either eliminated or
      substituted. Each construct was tested for its ability to promote transcription
      in vitro, using a rat testis nuclear extract. Disruption of either motif reduced
      in vitro transcription to about 30% of control levels, while mutations of both
      elements abolished transcription. Two sites were selected inside each motif and
      altered by point mutation. Each of four constructs, containing a mutation at -51,
      -48, -30, or -28, transcribed at 29% or less the efficiency of the parent
      construct. The DNA element at -55, TGAGGTCA, is homologous to a consensus cyclic
      AMP response element. The motif at -32, TCTTAT, is located at a position
      analogous to a TATA box. Substitution of the -32 motif with a consensus TATA box
      sequence, TATAAA, stimulated transcriptional activity about 3-fold. As measured
      by gel mobility shift, oligonucleotides encompassing the -32 motif and the
      consensus TATA box formed different DNA-protein complexes. However, the -32 motif
      oligonucleotide was recognized by nuclear proteins prepared from either liver or
      testis nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736669
TI  - The CpG-rich promoter of human LDH-C is differentially methylated in expressing
      and nonexpressing tissues.
AB  - A comparison of nucleotide sequences of murine Ldh-a and Ldh-c genes and human
      LDH-A, LDH-B, and LDH-C reveals that mouse Ldh-c has lost the CpG "island"
      present in the genes for the somatic isozymes. However, the human LDH-C gene has
      a CpG-rich region of 230 bp surrounding its promoter. Endonuclease sensitivity
      coupled with polymerase chain reaction (PCR) demonstrate the presence of nine
      heavily methylated sites in this region in different somatic cells. The same
      sites are specifically hypomethylated in expressing tissues. 3' sites bordering
      the CpG-rich region appear to be methylated in both expressing and nonexpressing
      tissues. Furthermore, the methylated promoter forms a specific complex in vitro
      with a methyl-DNA binding protein. Evolutionary and functional implications of
      these observations are discussed.

PMID- 7736670
TI  - The making of a spermatozoon: a molecular perspective.

PMID- 7736671
TI  - Use of urine albumin measurement as a replacement for total protein.
AB  - We have investigated the replacement of urine total protein estimations for the
      assessment of glomerular permeability, by the measurement of urine albumin
      excretion using a latex particle enhanced immunoturbidimetric assay. An initial
      screen was performed using Albustix to assess the sample pre-dilution necessary
      for immunoanalysis. A total of 167 24-hour urine samples were analysed and urine
      albumin concentration correlated well with that of urine total protein (r = 0.93)
      over the range 0-16,800 mg/l. This protocol provides a more cost effective and
      analytically valid assessment of glomerular permeability.

PMID- 7736672
TI  - Quantitation of proteinuria in kidney transplant patients: accuracy of the
      urinary protein/creatinine ratio.
AB  - The follow-up of renal function in kidney transplant patients requires sensitive
      and specific parameters which allow the detection of clinically significant
      changes. In this prospective study, we have evaluated the accuracy of the urinary
      protein/creatinine ratio (UP/UCreat), determined in morning urine specimens, in
      assessing 24-hour proteinuria (P24). Fivehundred and twenty paired samples were
      provided by 133 kidney transplant patients. The correlation coefficient of the
      linear regression was 0.93 in both in the first set of paired samples (133
      samples) and in all paired samples (520 samples). In complete urine collections,
      the UP/UCreat predicted the level of proteinuria with both a good specificity (95
      to 99%) and sensitivity (97 to 99%) at different levels of 24-hour protein
      excretion. The intraindividual coefficients of variation of P24 and UP/UCreat
      were evaluated in 82 patients (442 samples) and were 23% and 29% respectively.
      These results confirm that the UP/UCreat ratio in morning samples is a reliable
      estimate of the 24-hour proteinuria in kidney transplant patients. Additionally,
      its variation appears to accurately reflect changes in the rate of protein
      excretion.

PMID- 7736673
TI  - Pentoxifylline reduces proteinuria in insulin-dependent and non insulin-dependent
      diabetic patients.
AB  - Pentoxifylline is a drug with hemorheological actions used in the management of
      microcirculatory abnormalities, such as those usually seen in diabetic patients.
      The drug has been successfully used in improving peripheral and central
      circulation, as well as proteinuria of long-term diabetes. With the hypothesis
      that pentoxifylline reduces proteinuria in patients with IDDM and NIDDM, with a
      wide range of urinary protein excretion, 86 diabetic patients were studied. Forty
      one patients with IDDM were stratified in 2 subgroups: one of 18 patients with
      microalbuminuria, and the other of 23 patients with overt proteinuria. In the
      same way, 45 patients with NIDDM were divided in 2 subgroups: one of 23 patients
      with microalbuminuria, and the other of 22 patients with proteinuria. Patients in
      each subgroup were randomized to receive either placebo or pentoxifylline 1,200
      mg/d, during 4 months, using a double blind design. At the beginning of the study
      and after treatment, 24-hour urinary albumin excretion was measured by
      nephelometry in each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736674
TI  - Renal hemodynamic and histological consequences of diets high in unsaturated fat,
      protein or sucrose in obese Zucker rats.
AB  - The objective of this study was to determine the long-term effect of different
      dietary macronutrients on renal hemodynamics in obese Zucker rats. Female obese
      (fa/fa) Zucker rats were allowed to eat control chow (ObCL) or diets high in
      unsaturated fat (ObHF), protein (ObHP) or sucrose (ObHS) for a period of 24
      weeks. Lean chow fed (LnCL) Zucker rats served as lean controls. After 24 weeks
      of dietary treatments, glomerular filtration rate (GFR, ml/mg/g, mean +/- SE) of
      ObHP and ObHS (0.38 +/- 0.06 and 0.27 +/- 0.05) rats were significantly (p <
      0.005) lower than ObCL (0.74 +/- 0.05) and ObHF (0.88 +/- 0.1) rats. In a similar
      manner, the effective renal plasma flow (ERPF, ml/min/g) was significantly (p <
      0.005) lower in ObHP and ObHS (1.28 +/- 0.16 and 1.04 +/- 0.2) than ObCL (2.46 +/
      0.31) or ObHF (2.85 +/- 0.25) rats. The ObHF rats appeared "protected" since
      they had similr GFR and ERPF but less proteinuria and glucosuria than ObCL rats.
      Histological examination of renal tissue from ObHP and ObHS fed rats revealed
      significant (p < 0.005) increase in sclerosis relative to ObCL rats. The
      sclerosis of renal tissue in ObHF was minimized and was found to be similar to
      ObCL rats. The mean arterial pressure and heart rates were similar in all dietary
      treated obese Zucker rats. When comparing obese and lean controls, ObCL rats had
      significantly (p < 0.03) lower GFR (0.74 +/- 0.05 vs 0.92 +/- 0.05) but similar
      ERPF (2.46 +/- 0.3 vs 2.82 +/- 0.12) than LnCL rats.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7736675
TI  - A case of autosomal dominant polycystic kidney disease complicated by minimal
      change nephrotic syndrome.

PMID- 7736676
TI  - Spontaneous cellulitis in nephrotic syndrome.

PMID- 7736677
TI  - The use of continuous arteriovenous hemofiltration in orthotopic liver
      transplantation.

PMID- 7736678
TI  - Methylene blue as a cause of chemical peritonitis in a patient on peritoneal
      dialysis.

PMID- 7736679
TI  - FSG in children.

PMID- 7736680
TI  - Intravenous pamidronate sodium therapy in immobilization-related hypercalcemia.

PMID- 7736681
TI  - Kidneys from pediatric donors: is the double implant a solution for adult
      recipients?

PMID- 7736682
TI  - Podocytes loose their adhesive phenotype in focal segmental glomerulosclerosis.
AB  - Podocytes in focal segmental glomerulosclerosis (FSGS) show injury and focal
      detachment from the glomerular basement membrane (GBM). We studied by
      immunofluorescence and light microscopy the distribution of components involved
      in the integrin mediated adhesion of podocytes to the GBM in one case of
      recurrent idiopathic FSGS which developed in a renal transplant. Two major
      integrin and actin distribution patterns were observed in podocytes depending on
      the stage of the disease. Alpha 5 integrin subunit showed a gradual loss in early
      FSGS and became undetectable in advanced FSGS. Alpha 3 integrin subunit and the
      beta 3 subunit of the vitronectin receptor lost their polarized expression and
      could be detected intracellularly in early FSGS, while in advanced stage both
      integrin subunits were mostly basally polarized. In addition staining for alpha 3
      was markedly decreased but enhanced for beta 3. Most of the podocytes in early
      FSGS showed significant loss of filamentous actin together with a nonpolarized
      distribution and a transient expression of the HAR/GP90 receptor. An altered
      matrix composition was also seen corresponding to the newly formed GBM. Based on
      these results we propose that podocytes loose their adhesive phenotype in early
      FSGS, which may contribute to the detachment of podocytes from the GBM.

PMID- 7736683
TI  - Intravenous methylprednisolone and oral alkylating agent therapy of prednisone
      resistant pediatric focal segmental glomerulosclerosis: a long-term follow-up.
AB  - Prednisone-resistant nephrotic syndrome (NS) due to focal segmental
      glomerulosclerosis (FSGS), the most common acquired disease requiring chronic
      dialysis and transplantation in children, has a low likelihood of response to
      alkylating agent therapy. This report summarizes the results of a 0.75-12.5
      (average 6.33) year follow-up of 32 pediatric cases of prednisone-resistant FSGS
      treated with a regimen of high-dose intravenous methylprednisolone (M-P) and
      alternate-day prednisone, plus an alkylating agent in 25/32. On last followup:
      21/32 were in remission [urine protein-to-creatinine ratios (Pru/Cru) < or =
      0.2]; 3/32 had mild proteinuria (Pru/Cru > 0.2-0.5); 2/32 had moderate
      proteinuria (Pru/Cru > 0.5-1.9); and 6/32 remained nephrotic (Pru/Cru > or =
      2.0). Of the incomplete or nonresponders; 3/11 progressed to end-stage renal
      failure; 5/11 had decreased creatinine clearances (CrCl): and 3/11 had persistent
      proteinuria with normal CrCl. All of the persistently nephrotic children, but
      none of the complete responders, developed decreased CrCl. All of the complete
      responders were able to stop treatment; four relapsed but responded well to
      retreatment. CONCLUSIONS: This regimen of methylprednisolone and alternate-day
      prednisone, with or without an alkylating agent, is effective in achieving
      sustained remissions and preserving normal renal function in the great majority
      of children with FSGS and prednisone-resistant NS.

PMID- 7736684
TI  - Steroid resistant nephrotic syndrome associated with spondyloepiphyseal
      dysplasia, transient ischemic attacks and lymphopenia.
AB  - Focal segmental glomerulosclerosis, nephrotic syndrome and chronic renal failure
      were associated with spondyloepiphyseal dysplasia, growth failure, lymphopenia
      and transient ischemic attacks leading to severe neurological symptoms in three
      children. Two boys and one girl developed the full syndrome at the age of 5, 6
      and 10 years. Positron emission tomography revealed perfusion defects of both
      cerebral and cerebellar arteries. A variant of the disease was found in two other
      children who had a nephrotic syndrome and terminal renal failure with only mild
      spondyloepiphyseal dysplasia, impaired growth and a normal cerebral function. It
      is concluded that there may be a close association between focal segmental
      glomerulosclerosis and spondyloepiphyseal dysplasias.

PMID- 7736685
TI  - SDS-PAGE patterns and polymeric albumin in proteinuria of lupus
      glomerulonephritis.
AB  - Proteinuria was characterized by SDS-PAGE and by immunoblotting with anti-human
      albumin sera for the detection of urinary polymers of albumin (PA) in 40 patients
      with biopsy proven lupus glomerulonephritis (LN) (6 pts class III WHO, 24 pts
      class IV, 10 pts class V) with various clinical presentations (nephrotic syndrome
      with normal or impaired renal function, 14 pts; urinary abnormalities with normal
      or impaired renal function, 21 pts; clinical remission, 5 pts); in 25 pts, for
      whom the characterization of proteinuria and the renal biopsy were performed at
      the same time, the activity and chronicity index scores were calculated. The
      mixed SDS-PAGE patterns, characterized by the presence of low molecular weight
      proteins, were the more frequently found; the mixed patterns were significantly
      associated with interstitial leukocyte infiltration (p = 0.05) and glomerular
      sclerosis (p = 0.046) and nonsignificantly associated with higher values of serum
      creatinine; no SDS-PAGE pattern had predictive value on functional outcome at 36
      months. Albumin polymers were present in 67% of pts; in active disease they were
      present in 33% of class III, in 100% of class IV and in 45% of class V WHO (p =
      0.026); PA were not present in 5 pts with clinical remission (4 class IV and 1
      class V WHO). The presence of PA was significantly associated with high values (>
      10) of activity index (p = 0.009) and with extracapillary proliferation (p =
      0.041). Serum creatinine was lower in patients without PA (Scr 1.0 +/- 0.4 mg/dl)
      than in those with PA (Scr 1.5 +/- 1.0 mg/dl), but the difference was not
      statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736686
TI  - Clinical pharmacokinetics of flurbiprofen and its enantiomers.
AB  - Flurbiprofen is a chiral nonsteroidal anti-inflammatory drug (NSAID) of the 2
      arylpropionic acid class. Although it possesses a chiral centre, with the S-(+)
      enantiomer possessing most of the beneficial anti-inflammatory activity, both
      enantiomers may possess analgesic activity and all flurbiprofen preparations to
      date are marketed as the racemate. Flurbiprofen exhibits stereoselectivity in its
      pharmacokinetics. Stereoselectivity is exhibited at the level of protein binding
      and metabolite formation. Hence, the data generated using nonstereoselective
      assays may not be used to explain the pharmacokinetics of individual enantiomers.
      The absorption of flurbiprofen is rapid and almost complete when given orally.
      The area under the plasma concentration-time curve of flurbiprofen is
      proportional to the dose administered to patients. Sustained release dosage forms
      are available, which may be beneficial due to the short terminal phase
      elimination half-life of conventional immediate release flurbiprofen (3 to 6
      hours). They may also decrease local gastrointestinal adverse effects. Although
      with these preparations the peak plasma drug concentration is reduced and time
      taken to achieve peak concentrations is prolonged, the bioavailability is the
      same as that with regular release counterparts. Flurbiprofen binds extensively to
      plasma albumin, apparently in a stereoselective manner. Substantial
      concentrations of the drug are attained in synovial fluid, which is the proposed
      site of action of NSAIDs. There is negligible R to S inversion after oral
      administration. Flurbiprofen is eliminated following extensive biotransformation
      to glucuro-conjugated metabolites. Conjugates are excreted in urine, and
      approximately 20% of flurbiprofen is eliminated unchanged. The excretion of
      conjugates may be tied to renal function as accumulation of conjugates occurs in
      end-stage renal disease, but not in young individuals or elderly patients.
      Although flurbiprofen is excreted into breast milk, the amount of drug
      transferred comprises only a small fraction of the maternal exposure. Significant
      drug interactions have been demonstrated for aspirin (acetylsalicylic acid),
      coumarins and propranolol. The relationship between concentration and anti
      inflammatory and analgesic effect has yet to be elucidated for this drug.

PMID- 7736687
TI  - Clinical pharmacokinetics of rifabutin.
AB  - The clinical effectiveness of rifabutin for prophylaxis of disseminated
      Mycobacterium avium complex infection has recently been demonstrated in HIV
      positive patients with low CD4 counts. Rifabutin is a newly marketed,
      semisynthetic antimycobacterial agent similar to rifampicin (rifampin) in
      structure and activity. However, rifabutin has important pharmacokinetic
      differences compared with rifampicin. Rifabutin has relatively low oral
      bioavailability; about 20% after single dose administration. With long term
      administration rifabutin induces its own metabolism and the metabolism of some
      other drugs. The elimination half-life of rifabutin is long (45 hours) but, as a
      result of a very large volume of distribution (> 9 L/kg), average plasma
      concentrations remain relatively low after repeated administration of standard
      doses. In vitro rifabutin is more active against M. avium-intracellulare complex
      and at least as active against M. tuberculosis as rifampicin. In vivo the
      advantage of rifabutin is less apparent due to its lower plasma concentrations at
      equivalent doses. Adverse effects are unusual at the recommended oral dosage of
      300 mg/day, but become common as the total daily dose approaches 1 g. Dose
      limiting toxicity consists of a polyarthralgia/arthritis syndrome, possibly
      complicated by uveitis. More clinical studies are needed to establish the role of
      rifabutin in combination therapy for M. avium-intracellulare complex and other
      mycobacterial infections.

PMID- 7736689
TI  - The importance of pharmacokinetic/pharmacodynamic surrogate markers to outcome.
      Focus on antibacterial agents.
AB  - Pharmacokinetic/pharmacodynamic surrogate relationships have been used to
      describe the antibacterial activity of various classes of antimicrobial agents.
      Studies that have evaluated these relationships were reviewed to determine which
      of these surrogate markers were further dependent on antimicrobial class. The
      fluoroquinolone and aminoglycoside agents exhibit concentration-dependent
      killing. Studies have demonstrated that peak serum concentration: minimum
      inhibitory concentration (MIC) and area under the serum concentration-time curve
      (AUC): MIC ratios are important predictors of outcome for these antimicrobial
      agents. Area under the inhibitory concentration-time curve (AUIC24) [i.e.
      AUC24/MIC] is a useful parameter for describing efficacy for these agents, while
      an adequate peak concentration: MIC ratio seems necessary to prevent selection of
      resistant organisms. For beta-lactam antibiotics, the duration of time that the
      serum concentration exceeds the MIC (T > MIC) was the significant
      pharmacokinetic/pharmacodynamic surrogate in cases where the bacterial inoculum
      was low, or where very sensitive organisms were tested. However, in studies using
      more resistant organisms or larger inoculum sizes there is some concentration
      dependence to the observed effect. Studies using reasonable dosage intervals have
      demonstrated covariance between T > MIC and AUC/MIC ratio for beta-lactam
      antibiotics. Since glycopeptide antibiotics display relatively slow but
      concentration-independent killing, and are cell wall active agents similar to
      beta-lactams, it has been presumed that T > MIC is the important pharmacokinetic
      surrogate related to efficacy for these agents. Some studies have shown that a
      concentration multiple of the MIC may be necessary for successful outcome with
      vancomycin. AUIC24 may prove to be an important pharmacokinetic surrogate if both
      time and concentration are indeed important parameters. To select an appropriate
      antimicrobial agent, the clinician must consider many patient-specific as well as
      organism-specific factors. Utilisation of known pharmacokinetic/pharmacodynamic
      surrogate relationships should help to optimise treatment outcome.

PMID- 7736688
TI  - Problems of delivery of monoclonal antibodies. Pharmaceutical and pharmacokinetic
      solutions.
AB  - Monoclonal antibodies to tumour-associated antigens have great theoretical
      potential for the specific targeting of radioactivity and anti-neoplastic agents
      to tumours. The clinical success of monoclonal antibody-based cancer diagnosis
      and therapy depends, however, on solving a number of pharmacokinetic delivery
      problems. These include: (i) slow elimination of monoclonal antibodies from the
      blood and poor vascular permeability; (ii) low and heterogeneous tumour uptake;
      (iii) cross-reactivity with normal tissues; (iv) metabolism of monoclonal
      antibody conjugates; and (v) immunogenicity of murine forms in humans. As a
      result of extensive pharmaceutical and pharmacokinetic research conducted over
      the past 10 to 15 years, several potential solutions to these delivery problems
      have been identified. Blood concentrations of antibody conjugates may be reduced
      through regional administration, the use of antibody fragments, interventional
      strategies and various pre-targeting techniques. Tumour uptake may be increased
      through administration of higher doses, or the use of agents to increase tumour
      vascular permeability. Tumour retention of antibody conjugates may be improved by
      inhibition of metabolism, by using more stable linkage chemistry. Alternatively,
      normal tissue retention may be decreased through the use of metabolisable
      chemical linkages inserted between the antibody and conjugated moiety. Very small
      antigen-binding fragments and peptides that exhibit improved tumour penetration
      and more rapid elimination from the blood and normal tissues have been prepared
      by genetic engineering techniques. Chimeric (mouse/human) and human monoclonal
      antibodies have been developed to circumvent the problem of immunogenicity.
      Future research will continue to be focused on improvements in the design of
      monoclonal antibodies for tumour targeting, with the ultimate goal of finally
      uncovering the 'magic bullet' envisioned by Paul Ehrlich almost a century ago.

PMID- 7736690
TI  - Models for placental transfer studies of drugs.
AB  - Pregnancy is a specific dynamic state, and the potential usefulness of caring for
      a disorder in the fetus or the mother is now well established. Previously,
      pregnant women have been excluded from clinical trials, therefore only a few
      studies concerning evaluation of the pregestational metabolism or transplacental
      transfer (TPT) of drugs exist. Questions regarding the TPT of drugs are extensive
      and complex. For example, does TPT occur at a given gestational age, in the
      context of a particular type of pathology or when a drug is administered by a
      certain dosage regimen? If this is the case, what is the rapidity of penetration
      of the products of conception by the drug (bearing in mind its physicochemical
      characteristics)? Need harmful adverse effects on the child be feared? Is such
      penetration desirable, of no consequence, or dangerous? Does the possibility
      exist of accumulation in the placenta, fetal tissue or amniotic fluid? Should
      such findings modify the therapeutic regimens of drugs given to expectant
      mothers? Exchange mechanisms are complicated and models developed in vitro only
      partially reflect the actual equilibria that exist between mother and fetus.
      These include: (i) the perfused cotyledon model, which while simple, elegant and
      inexpensive, offers only a localised, restricted and fixed view of pregnancy;
      (ii) isolated anatomical fractions that are informative, but which straddle the
      border between physiology and pharmacology; and (iii) the necessary study, using
      microsomes, of placental metabolic capacity (enzyme cartography). In vivo study
      of TPT is based upon various multicompartmental pharmacokinetic models, some of
      which have been relatively validated in animals. The simplest indicator for the
      in vivo evaluation of TPT of a drug in the human species is determination of a
      feto-maternal blood concentration ratio (usually performed at the time of
      placental separation). However, the usefulness and limitations of this parameter
      are controversial, and it would seem preferable to associate it with a
      pharmacokinetic profile of variations in blood concentrations established in the
      mother. Furthermore, any extrapolation of a single result to fetal and adjacent
      tissues must be done with the greatest caution. Although, no drug should be used
      in pregnancy unless there is a clear therapeutic indication, study of the TPT of
      therapeutically useful agents is essential to the understanding of their
      metabolism and is a prerequisite to the safe use of medications during pregnancy.

PMID- 7736691
TI  - Concentration-controlled trials. What does the future hold?

PMID- 7736692
TI  - Glaxo/MRS Young Investigator Prize. Endothelium-mediated vascular function in
      insulin-dependent diabetes mellitus.

PMID- 7736693
TI  - A map of the heart: gap junctions, connexin diversity and retroviral studies of
      conduction myocyte lineage.
AB  - 1. The heartbeat is co-ordinated by organized propagation of electrical
      excitation through cardiac muscle. Intercellular conduction and propagation of
      the cardiac action potential is dependent on electrical connections between
      myocytes, termed gap junctions. 2. In the last few years, our conception of the
      structure and function of cardiac gap junctions has been revised substantially.
      It seems that these structures show unexpected levels of specialization within
      the myocardium and they can no longer be viewed simply as passive conduits for
      the regulated movement of electrical current between heart muscle cells. 3. In
      this article, some of the contributions to this field by the author and his
      collaborators are summarized. Studies using confocal microscopy and digital
      imaging techniques to characterize the three-dimensional organization of
      electrical contacts between myocytes in the mature and developing heart are
      described, data on the unique expression and spatial distribution patterns of gap
      junctional subunit proteins (connexins) are given, and finally the author's
      current work on the differentiation of cardiac conduction tissues, and how this
      work arose from studies of gap junctions in the heart, is introduced.

PMID- 7736694
TI  - Circulating antibodies to cardiac protein-acetaldehyde adducts in alcoholic heart
      muscle disease.
AB  - 1. Serum samples from patients with alcoholic heart muscle disease and from
      control subjects with and without heart disease who did not drink to excess were
      screened by Western immunoblotting for antibodies to acetaldehyde-modified
      cardiac cytosolic proteins. 2. Two of the 64 control samples (from subjects with
      and without heart disease who were not drinking and from subjects with alcoholic
      liver disease) had detectable (IgG) antibody to acetaldehyde-modified cardiac
      proteins. 3. By contrast, 7 of 21 (33%) patients with alcoholic heart muscle
      disease had antibodies against cyanoborohydride-stabilized, acetaldehyde-modified
      human cardiac cytosolic protein antigens (P < 0.001). 4. Antibodies were of IgG
      class in six patients and IgA class in five. The molecular sizes of the protein
      antigens observed ranged from 58 to 120 kDa. 5. These results suggest that a
      proportion of patients with alcoholic heart muscle disease develop immunogenic
      cardiac protein-acetaldehyde adducts. The presence of antibodies to these adducts
      may be a marker for the diagnosis of this heart disease, or possibly for its
      pathogenesis.

PMID- 7736695
TI  - Impaired platelet aggregation after cardiopulmonary bypass in man: enhancement of
      collagen-induced aggregation in whole blood and plasma by adrenaline ex vivo.
AB  - 1. We tested the effect of intravenous adrenaline at 0.55-1.10 nmol min-1 kg-1
      (for 3-8 min, at 7-10 min post bypass; n = 7) on both microaggregation in
      hirudinized whole blood, using platelet counting, and macroaggregation in
      platelet-rich plasma, using optical aggregometry. Control (n = 12) blood samples
      were taken before and at 10 and 20 min after bypass. 2. Post-bypass plasma
      adrenaline levels (nmol/l) increased slightly in controls (1.0 versus 0.7 at 10
      min, medians; P = 0.05) and markedly with adrenaline infusion (36 versus 0.5
      before infusion, P = 0.02). Microaggregation (percentage decrease in single
      platelets) in stirred blood, reflecting largely ADP-dependent 'spontaneous'
      aggregation, was not influenced by adrenaline infusion. In contrast, collagen
      (0.2 microgram/ml)-induced microaggregation in blood was enhanced by adrenaline
      (92% versus 41%, P = 0.02), with no change in controls (60% versus 53%, P =
      0.61). 3. In controls, collagen (0.6 microgram/ml)-induced macroaggregation in
      platelet-rich plasma (extent of increase in light transmission, cm) was impaired
      at 10 min post bypass (5.3 versus 12.1 before bypass, P = 0.01), but was enhanced
      by adrenaline (7.0 versus 3.6 before infusion, P = 0.02). Platelet counts (x
      10(9)/l) were decreased postbypass (155 versus 220, P = 0.02) and were not
      influenced by adrenaline infusion (167, P = 0.93).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7736696
TI  - Effects of insulin-like growth factor-I and growth hormone on the net flux of
      amino acids across the hind limbs in the surgically traumatized pig.
AB  - 1. After surgery three groups of six female pigs weighing on average 52.2 kg (SD
      3.5) received vehicle, recombinant insulin-like factor-1 (364.4 micrograms day-1
      kg-1) or recombinant human growth hormone (467.7 m-i.u. day-1 kg-1) for two post
      operative days. Vehicle and peptides were infused intravenously together with
      total parenteral nutrition providing 129 kJ day-1 kg-1 non-protein calories and
      0.35 g N day-1 kg-1. 2. On both post-operative days the mean concentration of
      insulin-like growth factor-1 in arterial blood samples was clearly below
      presurgical levels in animals receiving vehicle or recombinant human growth
      hormone, whereas recombinant human insulin-like growth factor-1 infusions more
      than restored insulin-like growth factor-1 concentrations. These last samples,
      however, contained significantly (P < 0.05) less insulin than those from other
      animals. 3. Infusion of recombinant human growth factor was often associated with
      higher circulating levels of amino acids compared with recombinant human insulin
      like growth factor-1 infusions. Despite this, both hormones significantly (P <
      0.05) increased the hind limb net balance of total amino acids on post-operative
      day 1. Net balances of -44.2, +69.5 and +100.9 mumol/min (pooled SE 35.3) were
      associated with infusion of vehicle, recombinant human insulin-like growth factor
      1 and recombinant human growth hormone respectively. This response was also
      closely reflected in the group of non-essential amino acids. 4. The net efflux of
      alanine from the hind limbs was also significantly (P < 0.002) reduced, whereas
      glutamine was less affected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736697
TI  - Insulin unresponsiveness of tubular monovalent cation transport during fructose
      induced hypertension in rats.
AB  - 1. Hyperinsulinaemia is considered to be a pathogenic factor for human and
      experimental hypertension. Thus, the contribution of the known insulin-stimulated
      tubular sodium reabsorption to this aetiological process has to be discussed. 2.
      Rats fed a fructose-enriched diet develop hyperinsulinaemia and hypertension,
      providing a model for studying the regulation of the tubular sodium handling and
      its possible relationship to hypertension. For this purpose, the sodium transport
      capacity of isolated nephron segments from control rats and from rats fed a
      fructose-enriched diet was investigated by measurement of ouabain-sensitive 86Rb
      uptake and of the hydrolytic activity of Na,K-ATPase. The number and affinity of
      insulin receptors were estimated from the specific [125I]insulin binding. 3. In
      rats fed a fructose-enriched diet, mild hypertension developed during the 14-day
      fructose diet. There were no differences, along the nephron, in basal 86Rb
      uptakes and ATPase activities between control rats and fructose-induced
      hypertensive rats. In control rats, insulin stimulated 86Rb uptake in the
      proximal convoluted tubule and cortical collecting duct, but exhibited an
      inhibitory action in the medullary thick ascending limb. In contrast, in fructose
      induced hypertensive rats, 86Rb influx remained unresponsive to insulin
      concentrations ranging from 10(-11) to 10(-7) mol/l in the proximal convoluted
      tubule and cortical collecting duct. In the medullary thick ascending limb, the
      threshold of inhibition was displaced from 10(-11) mol/l up to 10(-7) mol/l.
      Insulin binding to the proximal convoluted tubule, medullary thick ascending limb
      and collecting duct were similar in control rats and in rats fed a fructose
      enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736698
TI  - Development of decreased insulin-induced glucose transport in skeletal muscle of
      glucose-intolerant hybrids of diabetic GK rats.
AB  - 1. The effect of glucose intolerance on insulin-stimulated glucose transport in
      isolated skeletal muscles was investigated in male F1 hybrids of spontaneously
      diabetic GK (Goto-Kakizaki) and control Wistar rats at 1 and 2 months of age. 2.
      Hybrid rats are characterized by markedly impaired glucose-induced insulin
      secretion. The area under the blood glucose curve was significantly higher
      following an intraperitoneal glucose injection (2 g/kg) in hybrid rats in both
      age groups than in the control rats (P < 0.001). In 2-month-old hybrid rats the
      incremental area under the insulin curve during the intraperitoneal glucose
      tolerance test was not different from that of control rats. Serum cholesterol,
      triacylglycerol or plasma free fatty acid levels did not differ between the
      groups. Fasting and post-prandial plasma glucose concentrations were elevated in
      2-month-old hybrid rats compared with control rats (54%, P < 0.05, and 27%, P <
      0.05, respectively), but were not different in 1-month-old rats. Plasma insulin
      did not differ between the hybrid and control rats in the fasting or post
      prandial state at either age studied. 3. The insulin dose-response curves for 3-O
      methylglucose transport did not differ between 1-month-old hybrid and control
      rats for either the soleus or epitrochlearis muscle. The insulin dose-response
      curve for the epitrochlearis, but not for the soleus, muscle from 2-month-old
      hybrid rats was shifted to the right compared with the curve from the control
      animals (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736699
TI  - Human erythrocyte membrane fluidity and calcium pump activity in primary combined
      hyperlipidaemia.
AB  - 1. Human erythrocyte membrane cholesterol, fluidity and basal and calmodulin
      stimulated calcium pump (Ca(2+)-Mg(2+)-ATPase) activities were compared in 24
      patients with primary combined hyperlipidaemia and 20 age-matched normolipidaemic
      control subjects. 2. There was no correlation between serum and membrane
      cholesterol. Despite the differences in serum cholesterol levels between the two
      groups, membrane cholesterol levels were similar. 3. 1,6-Diphenyl-1,3,5
      hexatriene anisotropy was lower in the hyperlipidaemic group, suggesting
      increased fluidity in the hydrocarbon core of the phospholipid membrane bilayer.
      4. Basal calcium pump activity was lower in the hyperlipidaemic group with
      increased membrane fluidity. 5. These results suggest that membrane adaptive
      mechanisms can maintain membrane cholesterol within a narrow range, that serum
      triacylglycerol is more important than serum cholesterol in determining membrane
      fluidity and that increased membrane fluidity reduces basal calcium pump
      activity.

PMID- 7736700
TI  - Fetal and maternal lipoprotein metabolism in human pregnancy.
AB  - 1. Lipid, apolipoprotein concentration and composition were determined in
      maternal venous and umbilical arterial and venous blood at delivery by elective
      Caesarean section in 13 full-term pregnancies and in 25 healthy non-pregnant
      females. The indications of Caesarean section were a previous Caesarean section
      or breech presentation. None of the women was in labour and there were no other
      complications of pregnancy or fetal distress. 2. The objectives of the study were
      to establish whether the placenta has a role in feto-maternal cholesterol
      metabolism through either synthesis or transplacental cholesterol flux. The
      potential for free cholesterol diffusion between mother and fetus and rates of
      cholesterol esterification and transfer between lipoproteins were determined and
      related to the differences in composition between fetal and maternal
      lipoproteins. 3. Pregnant women had raised levels of all lipid and lipoprotein
      fractions compared with control subjects. The greatest increases were in free
      cholesterol and triacylglycerol (P < 0.0001). Lipoprotein (a) levels were
      significantly greater in the pregnant women [112 (12.2) mg/l] than in the control
      women [50 (10.0) mg/l]. 4. The only significant correlation between maternal and
      fetal lipoprotein concentrations was in lipoprotein (a) levels (r = 0.791, P =
      0.002). In both umbilical venous and arterial blood, concentrations of very-low-
      and low-density lipoproteins, particularly apolipoprotein B, cholesteryl ester
      and triacylglycerol, were lower than in maternal blood (P < 0.0001), but high
      density lipoprotein levels were similar. 5. There was no umbilical arteriovenous
      differences in lipoprotein concentration or composition. This suggests that
      cholesterol synthesis or free cholesterol diffusion does not occur in the
      placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736701
TI  - Dual-energy X-ray absorptiometry measurements of body composition: effects of
      depth and tissue thickness, including comparisons with direct analysis.
AB  - 1. There are few data regarding the accuracy of Hologic QDR-1000W dual-energy X
      ray absorptiometry for the measurement of body composition. In two studies, one
      in an in vitro experimental system using oil and water mixtures and the other in
      samples of pork meat, the effect of depth and tissue thickness on the measured
      composition was assessed. In the latter study the measured fat mass was compared
      with that measured by direct analysis. 2. All data indicated a trend in the
      measured fat mass with depth, such that more fat was measured at extremes of
      depth (< 10 cm and > 25 cm) than at intermediate depths. 3. In samples of meat
      weighing approximately 55 kg, dual X-ray absorptiometry significantly under
      estimated the absolute fat mass compared with direct analysis (mean 20.4 +/-
      1.65%) by 5-8% or 1-4 kg of fat. 4. These findings are of direct relevance to
      both clinical and research work using this technique to measure body composition,
      in particular in circumstances in which changes in body composition and/or tissue
      thickness are anticipated.

PMID- 7736702
TI  - Effect of fenspiride on pulmonary function in the rat and guinea pig.
AB  - 1. Fenspiride is an anti-inflammatory agent that may have a role in reversible
      obstructive airways disease. Small, but significant, improvements have been seen
      in airways function and arterial oxygen tension in patients with mild chronic
      obstructive pulmonary disease. These changes have been attributed to the anti
      inflammatory properties of the drug. However, airways function can be improved by
      other means, e.g. improved ventilation/perfusion ratio or reduced airways
      resistance. The possibility that fenspiride may have actions other than anti
      inflammatory was investigated in two animal species. 2. In the rat, actions on
      the pulmonary circulation were investigated in the isolated perfused lung, but
      fenspiride proved to be a poor pulmonary vasodilator, showing only a small
      reversal of the raised pulmonary artery pressure induced by hypoxia. 3.
      Ventilation was measured in the anaesthetized rat using whole-body
      plethysmography. Fenspiride caused no increase in ventilation or changes in
      arterial blood gases. However, a profound hypotensive action was observed with
      high doses. 4. The possibility that a decrease in airways resistance (R(aw))
      might occur with fenspiride was investigated in anaesthetized guinea pigs.
      Capsaicin (30 mumol/l) was used to increase baseline R(aw) through
      bronchoconstriction. Fenspiride gave a dose-dependent partial reversal of the
      raised R(aw), and its administration by aerosol proved as efficacious as the
      intravenous route. In addition, the hypotensive side-effect found with
      intravenous injection was alleviated by aerosolized fenspiride.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7736703
TI  - Sulphonamides as anti-inflammatory agents: old drugs for new therapeutic
      strategies in neutrophilic inflammation?
AB  - 1. It is well known that neutrophils act as mediators of tissue injury in a
      variety of inflammatory diseases. Their histotoxic activity is presently thought
      to involve proteinases and oxidants, primarily hypochlorous acid (HOCl). This
      oxidant is also capable of inactivating the specific inhibitor of neutrophil
      elastase (alpha 1-antitrypsin), thereby favouring digestion of the connective
      matrix. 2. In the present work, we found that sulphanilamide and some
      sulphanilamide-related anti-inflammatory drugs such as dapsone, nimesulide and
      sulphapyridine reduce the availability of HOCl in the extracellular
      microenvironment of activated neutrophils and prevent the inactivation of alpha 1
      antitrypsin by these cells in a dose-dependent manner. The ability of each drug
      to prevent alpha 1-antitrypsin from inactivation by neutrophils correlates
      significantly with its capacity to reduce the recovery of HOCl from neutrophils.
      Five other non-steroidal anti-inflammatory drugs were completely ineffective. 3.
      Therefore, sulphanilamide-related drugs, i.e. dapsone, nimesulide and
      sulphapyridine, have the potential to reduce the bioavailability of neutrophil
      derived HOCl and, in turn, to favour the alpha 1-antitrypsin-dependent control of
      neutrophil elastolytic activity. These drugs appear as a well-defined group of
      agents which are particularly prone to attenuate neutrophil histotoxicity. They
      can also be viewed as a previously unrecognized starting point for the
      development of new compounds in order to plan rational therapeutic strategies for
      controlling tissue injury during neutrophilic inflammation.

PMID- 7736704
TI  - Cigarette smoke stimulates release of neutrophil chemotactic activity from
      cultured bovine bronchial epithelial cells.
AB  - 1. Recruitment of neutrophils into the airway is a prominent feature of chronic
      bronchitis, a syndrome often associated with exposure to cigarette smoke. Since
      bronchial epithelial cells are the 'first' lung cells to come into contact with
      smoke, these cells may be responsible for neutrophil recruitment into the airway
      by release of neutrophil chemotactic activity in response to cigarette smoke. 2.
      To evaluate this hypothesis, we prepared bovine bronchial epithelial cells and
      measured their ability to release neutrophil chemotactic activity following
      exposure to cigarette smoke. Bronchial epithelial cells were prepared by
      overnight digestion with protease, filtered through 100-microns Nitex mesh and
      resuspended in Dulbecco's modified Eagle medium supplemented with 10% fetal calf
      serum and antibiotics and cultured at 2 x 10(6) cells in 2 ml of medium in 35-mm
      culture dishes. After 4 days, dishes were rinsed and refed with medium without
      fetal calf serum and incubated with and without 1:10 diluted smoke extract for 6
      h at 37 degrees C. The neutrophil chemotactic activity of the supernatant fluids
      was measured by the blindwell chamber technique. 3. Cigarette smoke itself added
      to medium did not stimulate chemotaxis. In contrast, cigarette smoke did
      stimulate the release of neutrophil chemotactic activity from bovine bronchial
      epithelial cells [15 +/- 3 (control) versus 74 +/- 5 (smoke), P < 0.01]. 4. This
      neutrophil chemotactic activity was dialysable, pepsin and acid stable, heat
      sensitive and lipid extractable. Sephadex G-75 column chromatography demonstrated
      two peaks of neutrophil chemotactic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736705
TI  - Hering-Breuer reflexes in high-altitude infants.
AB  - 1. Pulmonary ventilation was found to be similar in high-altitude and low
      altitude newborn infants, but the breathing pattern was deeper and slower at high
      altitude (Mortola, J.P., Frappell, P.B., Frappell, D.E., Villena-Cabrera, N.,
      Villena-Cabrera, M., Pena, F., Am Rev Respir Dis 1992, 46: 1206-9). We questioned
      the contribution of vagal reflexes to these differences in breathing pattern. 2.
      Measurements were performed on high-altitude (La Paz, Bolivia, 3600-4050 m,
      inspired O2 pressure approximately 92 mmHg, n = 34) and low-altitude infants
      (Santa Cruz, Bolivia, 400 m, PIO2 approximately 141 mmHg, n = 26). The strength
      of the Hering-Breuer inspiratory inhibitory reflex was estimated from the
      inspiratory time during a respiratory effort against airways closed at end
      expiration (Tloccl). The strength of the Hering-Breuer expiratory facilitatory
      reflex was estimated from the expiratory duration when airways were occluded
      during expiration (TEoccl). 3. Tloccl was significantly longer than the open
      airways TI at both low and high altitude, but significantly more so
      (approximately 14%) at high altitude. TEoccl was longer than open-airways TE in
      both groups of infants, but significantly less so at high altitude, whether
      TEoccl was compared between occlusions of similar tidal volume (on average,
      TEoccl at high altitude was 79% of that at low altitude) or similar airway
      pressure (87%). 4. The results suggest that at high altitude the contribution of
      the phasic volume-dependent vagal input to the inspiratory off-switch threshold
      is higher, and that the tonic vagal expiratory facilitation is lower, than at low
      altitude, presumably because of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736706
TI  - Effects of low-dose angiotensin II infusion on loop segment reabsorption: a free
      flow micropuncture study in rats.
AB  - 1. Little direct information is available on the actions of angiotensin II beyond
      the proximal tubule. We therefore studied the effect of a mildly vasoconstrictive
      dose of angiotensin II on tubular handling of water, sodium (Na+) and lithium
      (Li+) in rats by means of free-flow micropuncture at the late proximal tubule and
      the early distal tubule. 2. Endogenous angiotensin II was suppressed by
      pretreatment with enalapril. Compared with a control group, angiotensin II
      increased mean arterial pressure by 15 mmHg. Glomerular filtration rate decreased
      from 1.32 +/- 0.05 to 1.10 +/- 0.05 ml/min, Na+ excretion from 0.43 +/- 0.09 to
      0.13 +/- 0.03 mumol/min, fractional delivery of water at the late proximal tubule
      from 50.1 +/- 1.7 to 42.9 +/- 3.2%, fractional delivery of Na+ at the late
      proximal tubule from 46.5 +/- 1.3 to 39.1 +/- 3.5% and fractional delivery of
      water at the early distal tubule from 26.4 +/- 1.4 to 21.9 +/- 1.0% (P < 0.05 for
      each variable). Fractional delivery of Na+ at the early distal tubule did not
      change significantly. 3. Similar experiments were performed during partial aortic
      constriction to exclude the effects of increased perfusion pressure. The data
      obtained were similar, except that in this group the fractional delivery of Na+
      at the early distal tubule decreased from 8.6 +/- 0.7 to 6.8 +/- 0.9% (P < 0.05).
      4. The relation between late proximal tubule Na+ delivery and Na+ reabsorption
      between late proximal and early distal tubule was not disturbed by angiotensin
      II. For water, however, this relation tended to shift to a higher reabsorption
      rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736707
TI  - Is allopurinol beneficial in the prevention of renal ischaemia-reperfusion injury
      in the rat?: evaluation by near-infrared spectroscopy.
AB  - 1. The role of allopurinol in the protection of kidney function following
      ischaemia-reperfusion injury has been investigated using the novel technique of
      near-infrared spectroscopy. 2. An in vivo model of rat kidney ischaemia was used,
      with the expected falls in blood and tissue oxygenation seen and confirmed by
      near-infrared spectroscopy. 3. Allopurinol infusion increased the rate of
      reperfusion of oxygenated blood seen in control rats (P < 0.05). 4. Allopurinol
      enhanced the rate of tissue oxygenation during early reperfusion (P < 0.01). 5.
      This study provides further evidence for the proposed benefits of allopurinol in
      ischaemia-reperfusion injury. Furthermore, the potential of near-infrared
      spectroscopy as a technique of value in interventional studies of this nature is
      confirmed.

PMID- 7736708
TI  - Relation between uroporphyrin excretion, acute attacks of hereditary
      coproporphyria and successful treatment with haem arginate.
AB  - 1. The increased urinary excretion of porphyrins as well as of their precursors
      was studied in a patient with hereditary coproporphyria during two acute attacks
      in which symptoms differed markedly in character and severity. 2. The increase in
      urinary coproporphyrin was similar in the 'mild' and in the 'severe' attack,
      indicating a lack of correlation between coproporphyrin level and clinical
      symptoms. 3. Aminolaevulinic acid, porphobilinogen and uroporphyrin exhibited
      significantly higher values during the 'severe' attack than during the 'mild'
      attack. During the severe attack these three compounds were increased 18-, 14-
      and 46-fold, respectively, compared with increases of 3-, 3- and 8-fold,
      respectively, during the mild attack. 4. The striking rise in the formation of
      uroporphyrin was reflected in the plasma porphyrin profile, which revealed
      predominance of uroporphyrin. In accordance with this finding, an increase in
      erythrocyte porphobilinogen deaminase of 130% was recorded. 5. The fluorescence
      emission spectra of saline-diluted plasma (excitation of 405 nm) showed a
      distinct peak at 618 nm during the 'severe' episode and a small peak during the
      'mild' attack, pointing to the possibility of diagnosing an attack simply by
      following the fluorometric screen of plasma. 6. The 'severe' attack of
      coproporphyria was treated with daily infusions of haem arginate, 3 mg/kg, every
      day for 4 days, at the end of which period a dramatic clinical response was
      observed. The relief of symptoms was found to be clearly related to the moderate
      decrease in uroporphyrin excretion observed rather than to the steep decline in
      the precursors.

PMID- 7736709
TI  - Superoxide dismutases in idiopathic pulmonary fibrosis.

PMID- 7736710
TI  - Prevention and management of osteoporosis.
AB  - The importance of osteoporosis as a health problem in the United States was
      underscored by the enthusiastic reception given to the two previous Clinical
      Symposia (1983 and 1987) written by Frederick S. Kaplan, MD. Along with
      discussions of the physiology of bone remodeling and pathophysiology of bone
      loss, this extensive revision clarifies the roles of estrogen, other hormones,
      and cytokines in bone maintenance and resorption. The author outlines the latest
      therapeutic guidelines, emphasizing the life-long preventive measures and medical
      interventions that can help halt the development of this preventable disorder.

PMID- 7736711
TI  - British Committee for Standards in Haematology 30th Anniversary Symposium.
      Harrogate, Yorks, United Kingdom, 25 April 1994. Abstracts.

PMID- 7736712
TI  - Myeloperoxidase activity and nuclear segmentation of maternal neutrophils during
      normal pregnancy.
AB  - Myeloperoxidase (MPO) activity and nuclear segmentation of neutrophils were
      measured in peripheral blood samples from 90 normal pregnant women, arranged in
      nine groups of ten each, every four weeks at 8-40 weeks gestation and from 25 non
      pregnant healthy female controls. A blood autoanalyser (Technicon H*1) was used
      to determine the mean peroxidase index (MPXI) and the lobularity index (LI) of
      circulating neutrophils. Mean MPXI levels in pregnancy decreased with gestation
      to a minimum at 20 weeks' gestation and increased thereafter to reach non
      pregnant levels at 36 weeks. Mean LI values did not change significantly with
      gestation, but were significantly lower throughout pregnancy compared to
      controls. There was no significant association between MPXI and LI. It could be
      postulated that the fall in MPXI during mid-gestation is due to degranulation of
      neutrophils and the subsequent rise at the end of pregnancy could be a
      consequence of enhanced MPO activity under the influence of oestrogens. Low LI
      suggests the production of immature neutrophils during pregnancy.

PMID- 7736713
TI  - Unusual bleeding manifestations of amyloidosis in patients with multiple myeloma.
AB  - We describe two patients who developed severe haemorrhagic complications. One
      manifested massive vaginal bleeding and the second haemopericardium with cardiac
      tamponade. In both cases histopathological examination showed subendothelial
      deposits of amyloid. Since other local and systemic causes of the haemorrhagic
      complications were excluded the bleeding was most probably due to amyloid
      angiopathy. Therefore, amyloid angiopathy should be considered in the
      differential diagnosis of bleeding in patients with amyloidosis associated with
      multiple myeloma.

PMID- 7736714
TI  - A case of intravascular malignant lymphomatosis (angiotropic lymphoma) with
      raised perinuclear antineutrophil cytoplasmic antibody titres--a hitherto
      unreported association.

PMID- 7736715
TI  - Rapid progression of 'retinoic acid syndrome' in the hypogranular variant of
      acute promyelocytic leukaemia, despite treatment with dexamethasone and
      conventional chemotherapy.

PMID- 7736716
TI  - Selective IgA deficiency and hyposplenism.

PMID- 7736717
TI  - British Blood Transfusion Society. Blood Component Special Interest Group
      Symposium. Towards 'purer and safer' blood components and blood products. London,
      United Kingdom, 5 May 1994. Abstracts.

PMID- 7736718
TI  - The role of plasmapheresis in myeloma patients with renal failure.

PMID- 7736719
TI  - Red cell distribution (RDW) in patients with erythrocytes containing Howell-Jolly
      bodies.

PMID- 7736720
TI  - Linguistic and conceptual control of visual spatial attention.
AB  - A theory of voluntary, top-down control of visual spatial attention is presented
      that explains how linguistic cues like "above," "below," "left," and "right" are
      used to direct attention from one object to another. The theory distinguishes
      between perceptual and conceptual representations of space and views attention as
      a set of mechanisms that establish correspondences between the representations.
      Spatial reference frames play an important part in this analysis. The theory
      interprets reference frames as mechanisms of attention, similar to spatial
      indices but with more computational power. The theory was tested in 11
      experiments that assessed the importance of linguistic distinctions between
      classes of spatial relations (basic, deictic, and intrinsic) and examined the
      flexibility with which subjects manipulated spatial reference frames.

PMID- 7736721
TI  - The multiconstituency approach to organizational performance assessment: a
      Canadian mental health system application.
AB  - This papers applies a multiconstituency approach to assessing organizational
      performance in Canadian general hospital psychiatric units and provincial
      psychiatric hospitals. In the absence of reliable and valid outcome measures,
      researchers and administrators have increasingly considered the views of external
      constituencies as a means of both defining the criteria for effective performance
      and actually assessing organizational performance. Key constituencies included
      psychiatric unit staff, psychiatric hospital administrators, and directors of
      community agencies providing mental health and related services. Opinions about
      organizational roles were found to exist among constituencies and among
      professional groups. Perceptions of organizational performance were highest for
      primary roles and substantially lowest for roles of secondary importance to the
      constituency. Future analyses of this type could help to validate the use of both
      constituency measures and more traditional performance measures. While
      constituency views may be seen as subjective, they are nevertheless key to
      building effective mental health service delivery systems.

PMID- 7736723
TI  - Public attitudes and intentions regarding tenants of community mental health
      residences who are neighbours.
AB  - A mail survey was conducted on a representative sample of 345 households in
      Winnipeg to examine public attitudes and behavioural intentions regarding tenants
      of community mental health residences who are neighbours. Vignette methodology
      was used to investigate the effects of mental illness labels (living in a
      community mental health residence vs. a normal residence), behavioural
      presentation (reflecting mild vs. severe disability), and sex of neighbours.
      Results showed behavioural presentation superseding labelling associated with
      tenancy in community mental health facilities in determining public attitudes
      toward and behavioural intentions regarding neighbouring. The study extends
      previous research by suggesting high levels of receptiveness on the part of
      community residents to having tenants as neighbours. Implications of the findings
      for improving the neighbourhood integration of tenants in community mental health
      residences are discussed.

PMID- 7736722
TI  - Case management with homeless women: a descriptive study.
AB  - This article presents the results of a three-year survey of the activities of two
      case managers following 25 homeless women with substance abuse problems. The case
      managers' activity record indicated that a great deal of the case managers'
      energy was devoted to providing direct, concrete services. More than half the
      clients received four weekly contacts, for an average total of two
      hours/client/week. Furthermore, direct support accounted for 42.2% of all
      contacts reported by the case managers, suggesting that, although case managers
      fill many different functions, establishing and maintaining a significant
      relationship with the participants constituted a major part of their work. The
      study confirms that a high staff-to-client ratio is required to respond to the
      multiple needs of this population.

PMID- 7736724
TI  - The 'ward-in-a-house': residential care for the severely disabled.
AB  - This paper is concerned with the care of the most difficult and severely disabled
      new patients presenting to mental health services in the U.K. Questions of
      definition will be examined and the clinical and social characteristics of the
      population discussed. Since the defining characteristics (and prevalence) of this
      group are strongly affected by the overall service context, the range of
      community provisions within one health district (Cambridge) will be described.
      Examples of a new kind of institutional solution-the 'ward-in-a-house'-will then
      be presented, together with the underlying principles of management and care. The
      benefits and limitations of the model will be discussed.

PMID- 7736725
TI  - Residents' perceptions of transcultural psychiatric practice.
AB  - A questionnaire was distributed to 190 psychiatry residents to analyze the impact
      of three factors on residents' perceptions of their transcultural practice:
      cultural identity of residents; degree of exposure to patients from different
      cultures; and training in cultural psychiatry. Results suggest that residents'
      perceptions vary according to the resident's cultural origin. The training in
      psychiatry and the degree of exposure to patients from different cultures had no
      significant influence on the residents' perceptions. Overall these results
      emphasize the necessity to revise the cultural content of residents' psychiatry
      curriculum to, among other things, raise residents' awareness of their own
      cultural identity.

PMID- 7736726
TI  - Training residents for community psychiatric practice: guidelines for curriculum
      development.

PMID- 7736727
TI  - Modelling diagnostic skills in the domain of skeletal dysplasias.
AB  - The diagnostic model used in the medical expert system Skeletal Dysplasias
      Diagnostician (SDD) is discussed. The model aims to capture the diagnostic skills
      of domain experts. Such skills represent high level strategies which apply across
      different medical domains and hence the presented model is relatively generic.
      Preliminary evaluation of an earlier version of the diagnostic model, which
      yielded promising results, has led to a considerably improved model. A sample
      consultation given in an appendix illustrates most aspects of the current model.
      The paper concludes by giving the authors' practical insights into the knowledge
      engineering of medical diagnostic systems.

PMID- 7736728
TI  - Kinesiological motion expert system.
AB  - Kinesiology builds on anatomical information by establishing which muscles
      contribute to human motion and to what extent. This 'body as machine' approach
      seeks to identify particular muscles as contractile 'engines'. The learning of
      muscular contributions to human motions based on long tables of origins,
      insertions, innervations, and actions is tedious and often incomplete based on
      author judgments of which muscles and motions to include. The kinesiological
      motion expert system (KMES) was developed so that students could easily select
      joints, actions, and tension types and receive computerized output listing the
      muscles that could contribute to the motion requested. In addition, a student can
      select a particular muscle and tension type and the program will return all of
      the motions that the selected muscle might contribute. The KMES was written in
      PDC Prolog and has a knowledge base of 1583 movements. Implementation of the KMES
      in kinesiology classes resulted in an increase in average student final scores of
      approximately 15% (F(3,190) = 12.11, P < 0.0001).

PMID- 7736729
TI  - Hydrophobic neighboring homology (HNH) dotplot: an approach for assessing
      structurally similar motifs in proteins.
AB  - Structural biology needs sensitive tools to detect homology between proteins of
      low sequence identity, but with closely related 3-D structures. Using a
      conventional dotplot method, we therefore introduced 2 concepts to improve the
      search for similarities between secondary structures of analyzed proteins:
      'hydrophobic neighboring homology' (HNH) and 'amino acid degeneracy classes'. The
      amino acids are grouped into 3 subsets: hydrophobic, hydrophilic and mimetic. A
      'Neighboring Similarity Index' (NSI) is calculated for every residue pair and
      quantifies its neighbor homology. By thresholding the homology matrix and
      filtering the dotplot, the homologous patterns are extracted. We have evaluated
      the efficiency and limits of the method using 21 protein pairs extracted from the
      Protein Data Bank (PDB), or selected from the recent literature. Globally, we
      again find the homologous structures (alpha-helices and beta-strands) of these
      pair proteins. The introduction of neighbor residue hydrophobicity in the
      conventional dotplot improves the alignment of proteins with low sequence
      identity (< 25%). HNH, written in standard ANSI C with the graphic library X11,
      under UNIX, is available on request.

PMID- 7736730
TI  - PC software library for the production of auditory stimuli in cognitive event
      related potential experiments.
AB  - Software which provides an interface to the features of the Sound Blaster Pro
      card for the IBM PC using MS-DOS is described. The library may be called from a
      Turbo Pascal version 6 program. It permits tones of specified frequency (500 Hz-8
      kHz in increments of 500Hz) and aversive noise to be turned on and off by a
      controlling program, during cognitive event-related potential paradigms. Tones
      are synthesized by hardware and noise is replayed from memory using the digital
      sound processor. The library provides the appropriate level of abstraction for
      the programmer designing such paradigms, by hiding the detail of the register
      level. It provides a model for programming the card in other high level languages
      and may be augmented to provide more complex stimuli, such as short segments of
      speech or music. The card when controlled by the library provides a versatile and
      cost effective alternative to an audiometer in the electrophysiological
      laboratory.

PMID- 7736731
TI  - A method for quantitative image assessment based on redundant feature
      measurements and statistical reasoning.
AB  - Advances in computer graphics and electronics have contributed significantly to
      the increased utilization of digital imaging throughout the scientific community.
      Recently, as the volume of data being gathered for biomedical applications has
      begun to approach the human capacity for processing, emphasis has been placed on
      developing an automated approach to assist health scientists in assessing images.
      Methods that are currently used for analysis often lack sufficient sensitivity
      for discriminating among elements that exhibit subtle differences in feature
      measurements. In addition, most approaches are highly interactive. This paper
      presents an automated approach to segmentation and object recognition in which
      the spectral and spatial content of images is statistically exploited. Using this
      approach to assess noisy images resulted in correct classification of more than
      97% of the pixels evaluated during segmentation and in recognition of geometric
      shapes irrespective of variations in size, orientation, and translation. The
      software was subsequently used to evaluate digitized stained blood smears.

PMID- 7736732
TI  - A SAS macro for residual deviance of ordinal regression analysis.
AB  - In this paper, a SAS macro is described for calculating the likelihood of the
      'saturated' model in the analysis of ordinal regression. The outcome variable is
      multinomial on an ordinal scale, while the explanatory variables can be nominal
      or ordinal. Several ordinal regression models may be fitted to the data. One
      method of testing for the goodness of fit of these regression models is by
      comparing the residual deviance with the chi 2 distribution. In SAS, PROC
      LOGISTIC may be used to fit this type of data with proportional odds model.
      Unfortunately, the residual deviance is not available from the output. Our SAS
      macro will supplement the SAS output so that the residual deviance test may be
      carried out. The data from an ongoing HIV study is used as an illustration.

PMID- 7736733
TI  - On computers and building blocks, APACHE II and HIV, and dark clouds.

PMID- 7736734
TI  - Monitoring cardiopulmonary resuscitation: role of blood and end-tidal carbon
      dioxide tension.

PMID- 7736735
TI  - Hemoglobin-based oxygen-carrying resuscitation fluids.

PMID- 7736736
TI  - Economic analysis of the intensive care unit: a dilemma.

PMID- 7736737
TI  - Changes in acetylcholine receptor number in muscle from critically ill patients
      receiving muscle relaxants: an investigation of the molecular mechanism of
      prolonged paralysis.
AB  - OBJECTIVE: Previous reports have described prolonged paralysis after the
      administration of muscle relaxants in critically ill patients. The purpose of
      this study was to examine possible pathophysiologic causes for this paralysis by
      measuring muscle-type, nicotinic acetylcholine receptor number in necropsy muscle
      specimens from patients who had received muscle relaxants to facilitate
      mechanical ventilation before death. DESIGN: Prospective laboratory study of
      human muscle collected at autopsy. SETTING: Medical and surgical intensive care
      units (ICUs) at a university hospital and a research laboratory. PATIENTS:
      Fourteen critically ill patients, with a variety of diagnoses, all of whom
      required mechanical ventilatory support before their deaths in the ICU and who
      underwent post mortem examination. Patients were arbitrarily divided into three
      groups, according to their total vecuronium dose and number of days mechanically
      ventilated before death. Three patients were in the control group (defined as
      dying within 72 hrs of initiation of ventilatory support and receiving a total
      dose of < 5 mg of vecuronium). Six patients were in the low-dose group (defined
      as requiring ventilatory support for > 3 days before death and receiving a total
      vecuronium dose of < or = 200 mg). Five patients were in the high-dose group
      (defined as requiring ventilatory support for > 3 days before death and receiving
      a total vecuronium dose of > 200 mg). INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Nicotinic acetylcholine receptor numbers as measured by specific 125I
      alpha-bungarotoxin binding to human rectus abdominis muscle obtained at autopsy
      were determined. In general, receptor number reflected the clinical requirements
      for the muscle relaxants of each patient. Patients who had increasing
      requirements for muscle relaxants before death had increases in receptor number,
      as compared with control values. CONCLUSIONS: The increase in nicotinic
      acetylcholine receptor number in muscle from patients with an increasing
      requirement for muscle relaxants before death suggests that nicotinic
      acetylcholine receptor up-regulation may underlie the increased requirements for
      muscle relaxants seen in some patients. Furthermore, these findings suggest that
      muscle relaxant-induced, denervation-like changes may at least be partially
      responsible for prolonged muscle paralysis after the long-term administration of
      muscle relaxants. This study may provide the first information into the molecular
      mechanisms underlying prolonged paralysis.

PMID- 7736738
TI  - Alterations in immune function following head injury in children.
AB  - OBJECTIVE: To investigate cellular and humoral immunity in children immediately
      after severe head injury and during the early recovery period. DESIGN:
      Prospective, observational study with factorial design. SETTING: Pediatric ICU of
      a university teaching hospital. PATIENTS: Fifteen children (median age 9.6 yrs,
      range 1.7 to 18) with head injury and Glasgow Coma Score of < or = 7.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Skin testing with seven
      standard antigens was performed and blood samples were obtained for the following
      measurements: total lymphocyte count and subsets; proliferative response to
      phytohemagglutinin, concanavalin A, and pokeweed mitogen; and immunoglobulin
      concentrations on days 1, 7, and 14 and 3 months after injury. The effect of
      patient plasma on phytohemagglutinin-induced proliferative responses of normal
      donor lymphocytes was also assessed at these times. Anergy was present in 71% of
      patients on day 1, 54% of patients on day 7, 31% of patients on day 14, and 18%
      of patients at 3 months. Total, helper, and suppressor T-cell counts were
      decreased on day 1, and the T-cell response to phytohemagglutinin was decreased
      on days 1, 7, and 14 compared with values at 3 months. B-cell counts were
      increased on day 1, followed by an increase in serum immunoglobulin
      concentrations 1 to 2 wks later. The B-cell response to pokeweed mitogen was
      unchanged over the 3-month study period. The phytohemagglutinin responses of
      normal donor lymphocytes were decreased when incubated with patient plasma
      obtained on day 7 after injury. CONCLUSIONS: Severe head injury in children is
      associated with depressed cell-mediated immunity. Plasma immunosuppressive
      factors may contribute to T-cell dysfunction.

PMID- 7736739
TI  - Do elderly patients overutilize healthcare resources and benefit less from them
      than younger patients? A study of patients who underwent craniotomy for treatment
      of neoplasm.
AB  - OBJECTIVE: Some physicians and academicians have suggested that limiting selected
      healthcare resources to the elderly will help curtail the rising cost of health
      care in the United States. In order to test this hypothesis in a specific medical
      context, we compared the cost of caring for younger (< 65 yrs) patients with that
      of caring for older (> or = 65 yrs) patients who underwent craniotomy for
      treatment of brain tumors. DESIGN: Prospective collection and review of data on
      patients undergoing craniotomy for tumor in our institution between February 1989
      and December 1991. SETTING: University teaching hospital. METHODS: Patients were
      divided into two groups: those < 65 yrs, and those > or = 65 yrs. Demographics,
      severity of illness, length of stay, hospital and surgical intensive care unit
      (ICU) costs and charges, ICU complications, procedures, and outcome variables
      were analyzed. RESULTS: Of 3,265 ICU patients admitted during the study period,
      data on 123 (3.8%) undergoing craniotomy for brain tumor were analyzed. There
      were no differences between the patient groups in length of ICU stay or hospital
      stay, final outcome at discharge from the hospital, quality of life, or hospital
      or ICU costs, despite the fact that elderly patients had a greater number of
      procedures and complications per patient, and higher Acute Physiology and Chronic
      Health Evaluation II (APACHE II) severity of illness scores on admission and
      discharge than younger patients. CONCLUSIONS: The assertion that the elderly may,
      under certain conditions, consume more healthcare resources and benefit less from
      them than younger patients must be tested for accuracy with regard to specific
      disease states. In the context of the disorder studied herein, the elderly do as
      well as the young. Without specific study of specific pathologic processes or
      surgical procedures, using age to limit access to resources remains an
      unsubstantiated, ideologic concept, rather than a scientifically proven cost
      saving measure.

PMID- 7736740
TI  - Increased serum nitrite and nitrate concentrations in children with the sepsis
      syndrome.
AB  - OBJECTIVES: To measure total serum nitrite and nitrate concentrations in children
      with the sepsis syndrome as an indicator of endogenous nitric oxide production.
      To determine if there is an association between total serum nitrite and nitrate
      concentrations and vascular responsiveness to norepinephrine. DESIGN: A
      prospective, clinical study. SETTING: Tertiary, multidisciplinary, pediatric
      intensive care unit. PATIENTS: Thirty-one children with the sepsis syndrome, 18
      of whom were also hypotensive. Sixteen critically ill children without signs of
      the sepsis syndrome served as controls. INTERVENTIONS: Blood samples were
      obtained from indwelling catheters. The norepinephrine dose to reach the age
      appropriate, 50th percentile mean arterial blood pressure was determined in
      patients receiving norepinephrine. MEASUREMENTS AND MAIN RESULTS: Total serum
      nitrite and nitrate concentrations were measured on the first three days after
      the recognition of the sepsis syndrome. Patients with the sepsis syndrome had
      increased mean total serum nitrite and nitrate concentrations (day 1, 118 +/- 93
      microM; day 2, 112 +/- 94 microM; day 3, 112 +/- 93 microM) vs. controls (43 +/-
      24 microM, p < .05) on all 3 days. When sepsis syndrome patients were separated
      into nonhypotensive and hypotensive groups, only the patients with hypotension
      had increased concentrations vs. controls on all three days (p < .05). Sepsis
      syndrome patients with hypotension also had higher total serum nitrite and
      nitrate concentrations (145 +/- 97 microM) than sepsis syndrome patients without
      hypotension (82 +/- 76 microM, p < .05) on day 1. In five patients receiving
      norepinephrine infusions, increased total serum nitrite and nitrate
      concentrations were associated with higher norepinephrine requirements to
      maintain an age-appropriate, 50th percentile mean arterial blood pressure on each
      of the three study days (day 1, rs = 0.821, p < .05; day 2, rs = 0.900, p < .05;
      day 3, rs = 0.872, p < .05). CONCLUSIONS: Children with the sepsis syndrome,
      particularly those patients with hypotension, have increased total serum nitrite
      and nitrate concentrations that likely reflect increased endogenous production of
      nitric oxide. Vascular hyporesponsiveness to norepinephrine during the sepsis
      syndrome may be, in part, a nitric oxide-mediated process.

PMID- 7736741
TI  - Invasive hemodynamic evaluation of sublingual captopril and nifedipine in
      patients with arterial hypertension after abdominal aortic surgery.
AB  - OBJECTIVES: To examine the central hemodynamic and blood gas responses to
      sublingual captopril and nifedipine administration in patients with arterial
      hypertension after abdominal aortic surgery. DESIGN: Prospective, randomized,
      parallel-group clinical study. SETTING: Twenty-nine-bed medical-surgical
      intensive care unit in a university hospital. PATIENTS: Twenty patients with
      arterial hypertension (mean arterial pressure of > or = 115 mm Hg) the day after
      abdominal aortic surgery. Patients with bilateral renal artery stenoses,
      identified with the preoperative angiogram, were excluded. INTERVENTIONS:
      Pressures were measured using intravascular catheters and cardiac output was
      determined by thermodilution for 2 hrs after captopril 25 mg (n = 10) or
      nifedipine 10 mg (n = 10) was administered by the sublingual route. MEASUREMENTS
      AND MAIN RESULTS: Captopril administration and nifedipine administration
      decreased mean arterial pressure (from 121 +/- 1 to 94 +/- 4 mm Hg and from 121
      +/- 2 to 94 +/- 2 [sem] mm Hg, respectively), pulmonary arterial pressure,
      pulmonary artery occlusion pressure, and right atrial pressure (p < .001 for all
      variables). Changes in heart rate and in cardiac output were not significant.
      PaO2 decreased after nifedipine, from 101 +/- 8 to 81 +/- 3 torr [13.5 +/- 1.1 to
      10.8 +/- 0.4 kPa] (p < .01), but not after captopril (104 +/- 9 to 100 +/- 7 torr
      [13.9 +/- 1.2 to 13.3 +/- 0.9 kPa]). Excessive or symptomatic decreases in blood
      pressure were not observed, nor was deterioration in renal function observed.
      CONCLUSIONS: Sublingual captopril and nifedipine were equally effective for the
      treatment of arterial hypertension after abdominal aortic surgery. Nifedipine,
      but not captopril, caused a deterioration in pulmonary gas exchange.

PMID- 7736742
TI  - Predictive ability of acute physiology and chronic health evaluation II scoring
      applied to human immunodeficiency virus-positive patients.
AB  - OBJECTIVE: To evaluate the predictive ability of the Acute Physiology and Chronic
      Health Evaluation II (APACHE II) prognostic scoring system when applied to human
      immunodeficiency virus (HIV) seropositive patients in the medical intensive care
      unit (ICU). DESIGN: A retrospective chart review. SETTING: An urban university
      hospital serving the local community population and also functioning as a
      tertiary care referral center. PATIENTS: All HIV-positive patients who were
      discharged from the Yale-New Haven Hospital medical ICU between October 1, 1986
      and September 30, 1991. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      APACHE II scoring significantly underestimated the mortality rate in our patient
      population (n = 161) (35.5% estimated vs. 44.1% observed, p < .025). When
      patients were evaluated according to total lymphocyte count, APACHE II scores
      accurately predicted the mortality rate of all patients with a total lymphocyte
      count of > or = 201 cells/mm3 (n = 112) (32.6% estimated vs. 33.0% observed).
      However, APACHE II scoring significantly underestimated the mortality rate in the
      group of patients with a total lymphocyte count of < or = 200 cells/mm3 (n = 36)
      (44.2% expected vs. 61.1% observed, p < .05), particularly those patients with
      pneumonia or sepsis (n = 14) (50.5% expected vs. 85.7% observed, p < .01).
      CONCLUSION: APACHE II scoring significantly underestimates mortality risk in HIV
      positive patients admitted to the medical ICU with a total lymphocyte count of <
      or = 200 cells/mm3. This finding is particularly true regarding patients admitted
      due to pneumonia or sepsis.

PMID- 7736743
TI  - Acute Physiology and Chronic Health Evaluation II scoring system in acute
      myocardial infarction: a prospective validation study.
AB  - OBJECTIVE: To study the usefulness of the Acute Physiology and Chronic Health
      Evaluation II (APACHE II) scoring system for prognostication of inhospital
      mortality in acute myocardial infarction. DESIGN: A prospective validation study.
      SETTING: A medical intensive care unit (ICU) at a university hospital. PATIENTS:
      Over a 3-yr period, 2,007 admissions of 1,714 patients with acute myocardial
      infarction were studied. In readmissions to the medical ICU during the same
      hospital stay, only the first admission was studied. MEASUREMENTS AND MAIN
      RESULTS: Mean age of the patients was 72 +/- 10 yrs. The medical ICU mortality
      rate was 13% and total hospital mortality rate was 16%. Mean APACHE II score was
      11.6 +/- 6.5. There was a close correlation between observed and predicted
      mortality rates in classes of patients with various APACHE II scores. Observed
      mortality in patients with scores of 20 to 24 was higher than the predicted
      mortality (p < .03). In this subgroup, 25% of the patients had a length of stay
      in the medical ICU of < 8 hrs. CONCLUSIONS: Inhospital mortality in patients with
      acute myocardial infarction could be accurately predicted with APACHE II scores.
      Prognostication was not as good in patients with a length of stay in the medical
      ICU of < 8 hrs.

PMID- 7736744
TI  - Evaluation of a new continuous thermodilution cardiac output monitor in
      critically ill patients: a prospective criterion standard study.
AB  - OBJECTIVE: To evaluate the accuracy of a new continuous cardiac output monitor
      (one based on the thermodilution principle) in critically ill patients. DESIGN:
      Criterion standard study. SETTING: Multidisciplinary intensive care unit in a
      university hospital. PATIENTS: Fourteen critically ill patients, with different
      diseases, requiring pulmonary artery catheterization. INTERVENTIONS: In two
      patients with a left ventricular assist system, a defined, sudden 1 L/min change
      in cardiac output was carried through to evaluate the in vivo response time of
      the continuous cardiac output monitoring system. In the remaining 12 patients,
      cardiac output was altered by varying the dose of catecholamines, by volume
      loading, or by varying the level of sedation. In four patients, a rapid infusion
      of cold saline was given through a central venous catheter to test the
      performance of the system under these conditions. MEASUREMENTS AND MAIN RESULTS:
      Cardiac output was monitored continuously. A total of 163 (13 to 18 per patient)
      bolus determinations of cardiac output were performed, using the conventional
      thermodilution technique and simultaneously using the indocyanine green dye
      dilution technique. The range of cardiac output was 3.8 to 15.6 L/min. The
      results of the continuous thermodilution method were compared with the results of
      the bolus thermodilution and the dye dilution methods, respectively. The mean
      difference (bias) +/- SD of differences (precision) was 0.35 +/- 1.01 L/min for
      continuous vs. bolus thermodilution and 0.34 +/- 1.01 L/min for continuous
      thermodilution vs. indocyanine green dye dilution. Linear regression
      (correlation) analyses were y = 0.95x + 0.76 (r2 = .91) for continuous and bolus
      thermodilution and y = 0.93x + 0.87 (r2 = .91) for continuous thermodilution and
      dye dilution. The 75% in vivo response time was 10.5 mins. The infusion of cold
      isotonic saline led to erroneous continuous cardiac output values. When the
      conventional bolus thermodilution and dye dilution techniques were compared, mean
      difference was -0.01 +/- 0.54 L/min and the results of linear regression analyses
      were y = 0.97x + 0.22 (r2 = .97). CONCLUSIONS: Continuous cardiac output
      measurement using the thermodilution technique is reasonably accurate and is
      reliable and applicable in routine clinical practice, and therefore may add to
      patient safety. However, the response time is too slow for the immediate
      detection of acute changes in cardiac output. Some clinical conditions such as
      the rapid infusion of cold solutions can interfere with the continuous cardiac
      output measurement. Conventional bolus thermodilution and indocyanine green dye
      dilution methods showed good agreement and can be used interchangeably.

PMID- 7736745
TI  - Subcutaneous oxygen tension: a useful adjunct in assessment of perfusion status.
AB  - OBJECTIVES: Using a new fluorescence-quenching optode which, unlike earlier
      oximeters, neither consumes oxygen nor generates heat, we sought to determine the
      effects of hemorrhage and resuscitation on subcutaneous PO2. Additionally, we
      compared the effects of resuscitation with diaspirin crosslinked hemoglobin, an
      oxygen-carrying solution, on subcutaneous PO2 to that of traditional
      resuscitative fluids. We also compared mean arterial pressure and central venous
      oxygen saturation, indirect indices of perfusion, to subcutaneous PO2, a direct
      index of perfusion. DESIGN: Prospective trial, randomized for selection of
      treatment regimen. SETTING: Shock-trauma laboratory of a medical university.
      SUBJECTS: Male Sprague-Dawley rats, weighing 260 to 380 g. INTERVENTIONS: Rats
      were bled 22 mL/kg and resuscitated, 1 min later, with either 66 mL/kg of
      lactated Ringer's solution, 22 mL/kg of human serum albumin, 22 mL/kg of blood,
      or 22 mL/kg of diaspirin crosslinked hemoglobin. A fifth group of animals was not
      resuscitated after hemorrhage. Subcutaneous PO2 and mean arterial pressure were
      monitored continuously throughout the experiment, while central venous oxygen
      saturation was measured intermittently. MEASUREMENTS AND MAIN RESULTS:
      Subcutaneous PO2 decreased in response to hemorrhage and, although it did
      increase after resuscitation with each fluid, no treatment was able to restore
      subcutaneous PO2 to baseline within 2 hrs postresuscitation. Subcutaneous PO2
      continued to decrease after hemorrhage in the unresuscitated animals. In
      contrast, mean arterial pressure was restored to baseline values in only blood-
      and diaspirin crosslinked hemoglobin-treated animals, although this effect was
      lost within 30 mins in the blood-treated group. Only blood restored the central
      venous oxygen saturation to baseline values in the early postresuscitation
      period. CONCLUSIONS: The fluorescence-quenching optode consistently followed
      changes in subcutaneous PO2 during hemorrhage and after resuscitation. Diaspirin
      crosslinked hemoglobin performed as well as blood in restoring peripheral
      perfusion, as measured by subcutaneous PO2, while both of these fluids were
      superior to either lactated Ringer's solution or albumin. Both whole blood and
      diaspirin crosslinked hemoglobin restored mean arterial pressure to baseline,
      although the effect of the latter was of a longer duration. The pressor effect of
      the crosslinked hemoglobin did not affect peripheral perfusion, as reflected by
      the values for subcutaneous PO2. Subcutaneous PO2 is a useful adjunct in
      assessment of the adequacy of peripheral perfusion and may help redefine targets
      for resuscitation.

PMID- 7736746
TI  - Yohimbine modulates diaspirin crosslinked hemoglobin-induced systemic
      hemodynamics and regional circulatory effects.
AB  - OBJECTIVE: Diaspirin crosslinked hemoglobin, a hemoglobin-based blood substitute,
      is proposed to be an effective resuscitative solution. It produces an immediate,
      but limited increase in blood pressure when administered to conscious or
      anesthetized rats. This vasoactivity is associated with an increase in blood flow
      to several major organs. It has been shown that alpha-adrenergic receptors in the
      peripheral vascular system are sensitized by diaspirin crosslinked hemoglobin in
      rats. The present study was conducted to determine the effect of yohimbine, an
      alpha 2-adrenergic receptor antagonist on systemic hemodynamics and regional
      circulatory effects of diaspirin crosslinked hemoglobin. DESIGN: Prospective,
      randomized comparison of cardiovascular effects of diaspirin crosslinked
      hemoglobin in control and yohimbine-pretreated rats. SETTING: Laboratory of
      experimental medicine. SUBJECTS: Male Sprague-Dawley rats weighing 300 to 350 g.
      INTERVENTIONS: Modified, highly purified, and heat-pasteurized hemoglobin
      (diaspirin crosslinked hemoglobin) in control and yohimbine-treated (2 mg/kg
      i.v.) rats. MEASUREMENTS AND MAIN RESULTS: The systemic hemodynamics and regional
      circulation were measured using a radioactive microsphere technique. Diaspirin
      crosslinked hemoglobin (400 mg/kg i.v.) produced an increase in blood pressure
      and total peripheral resistance, while heart rate, cardiac output, and stroke
      volume were not significantly altered in control rats. In yohimbine-pretreated (2
      mg/kg i.v.) animals, diaspirin crosslinked hemoglobin did not produce any change
      in heart rate, stroke volume, cardiac output, and total peripheral resistance,
      but a slight increase in blood pressure was observed compared with baseline
      values obtained after the administration of yohimbine. The increase in blood
      pressure induced by diaspirin crosslinked hemoglobin was significantly blocked by
      pretreatment with yohimbine. Yohimbine (2 mg/kg i.v.) per se decreased blood
      pressure, while other systemic hemodynamic parameters were not affected.
      Diaspirin crosslinked hemoglobin increased blood flow to the heart,
      gastrointestinal tract (stomach, small intestine, cecum, and large intestine),
      portal (spleen, mesentery, and pancreas) and skin, while blood flow to the brain
      (cerebral hemispheres, diencephalon, cerebellum, and brain stem), liver, kidneys,
      and musculoskeletal system was not affected in control rats. In yohimbine
      pretreated animals, diaspirin crosslinked hemoglobin produced an increase in
      blood flow to the heart, brain (cerebellum and brain stem), liver, small
      intestine, cecum, spleen, mesentery and pancreas, kidneys, skin and
      musculoskeletal system, while blood flow to the stomach and large intestine was
      not affected. Yohimbine pretreatment significantly attenuated the diaspirin
      crosslinked hemoglobin-induced increase in blood flow to the large intestine,
      mesentery, and pancreas. CONCLUSIONS: The cardiovascular actions of diaspirin
      crosslinked hemoglobin are partially mediated through alpha 2-adrenergic
      receptors. Adrenergic receptor antagonists may be useful in attenuating the
      pressor effect of diaspirin crosslinked hemoglobin while maintaining the regional
      perfusion.

PMID- 7736747
TI  - Accuracy and reproducibility of the measurement of actively circulating blood
      volume with an integrated fiberoptic monitoring system.
AB  - OBJECTIVE: Bedside monitoring of circulating blood volume has become possible
      with the introduction of an integrated fiberoptic monitoring system that
      calculates blood volume from the changes in blood concentration of indocyanine
      green dye 4 mins after injection. The aim of this investigation was to compare
      the blood volume estimate of the integrated fiberoptic monitoring system (group
      1) with the standard methods of blood volume measurement using Evans blue (group
      2), and indocyanine green measured photometrically (group 3). DESIGN: Prospective
      laboratory study. SETTING: Animal laboratory of a University's institute for
      experimental surgery. SUBJECTS: Eleven anesthetized, paralyzed, and mechanically
      ventilated piglets. INTERVENTIONS: A central venous catheter was used for the
      injection of the indicator dyes (Evans blue and indocyanine green). A fiberoptic
      thermistor catheter was advanced into the thoracic aorta. The fiberoptic catheter
      detects indocyanine green by reflection densitometry for the estimation of blood
      volume of the integrated fiberoptic monitoring system. Samples for the
      determination of Evans blue and indocyanine green concentrations were drawn from
      an arterial catheter in the femoral artery over a period of 17 mins after
      injection. MEASUREMENTS AND MAIN RESULTS: Measurements were performed during
      normovolemia, hypovolemia (blood withdrawal of < or = 30 mL/kg), and hypervolemia
      (retransfusion of the withdrawn blood plus an infusion of 10% hydroxyethyl starch
      [45 mL/kg]). Linear regression, correlation, and bias were calculated for the
      comparison of the blood volume estimates by the fiberoptic monitoring system
      (group 1) vs. the total blood volume estimates using Evans blue (group 2) and
      indocyanine green (group 3): group 1 = 0.82.group 2-26 mL; r2 = 82.71%; r = .91;
      n = 40; group 1-group 2 +/- 1 SD = -435 +/- 368 mL; group 1 = 0.79.group 3 + 50
      mL; r2 = 74.81%; r = .87; n = 28; group 1-group 3 +/- 1 SD = -506 +/- 374 mL.
      CONCLUSIONS: The results demonstrate that the blood volume estimate of the
      fiberoptic monitoring system (group 1) correlates closely with the total blood
      volume measurement using Evans blue (group 2) and indocyanine green (group 3).
      Trapped indicator in the packed red cell column after centrifugation of the blood
      samples may account for an overestimation of group 2 and group 3 of approximately
      10% to 14%, but there still remains a proportional difference of 10% between
      group 1 vs. group 2 and vs. group 3. This difference is due to the longer mixing
      times of group 3 (16 mins) and group 2 (17 mins), during which they are
      distributed in slowly exchanging blood pools. It seems that the blood volume
      estimate of the fiberoptic monitoring system (group 1) represents the actively
      circulating blood volume and may be useful for bedside monitoring.

PMID- 7736748
TI  - Decreased bacterial adherence and biofilm formation on chlorhexidine and silver
      sulfadiazine-impregnated central venous catheters implanted in swine.
AB  - OBJECTIVE: To determine if antiseptic central venous catheters impregnated with
      silver sulfadiazine and chlorhexidine (antiseptic) reduce bacterial adherence and
      biofilm formation without producing local or systemic toxicity. DESIGN:
      Prospective, randomized, controlled trial. SETTING: Experimental laboratory in a
      university teaching hospital. SUBJECTS: Ten outbred New Hampshire pigs.
      INTERVENTIONS: Nonimpregnated (control) and antiseptic-impregnated catheters were
      inserted intravascularly into swine for 7 days. After explantation, the catheters
      were assessed for bacterial adherence and biofilm formation, and the surrounding
      tissue was assessed for signs of toxicity. Before retrieval, systemic
      concentrations of antimicrobials were determined. MEASUREMENTS AND MAIN RESULTS:
      Sequential roll plate and centrifuging were used to detect moderately and tightly
      adherent bacteria on the outer and luminal surfaces of the catheter. The presence
      of biofilm was detected by scanning electron microscopy. Tissues surrounding the
      catheters were examined histopathologically; systemic concentrations of
      chlorhexidine, sulfadiazine, and silver were determined by atomic absorption and
      high-performance liquid chromatography. As compared with the controls, antiseptic
      catheters had significantly (p < .01) fewer moderately and tightly adherent
      bacteria on outer and luminal surfaces, and fewer adherent bacteria when outer
      surfaces alone were examined (p < .01). Scanning electron microscopy showed
      bacterial biofilm and adherence on the control catheters but not on the
      antiseptic catheters. There were no abnormal histopathologic changes associated
      with the test catheter, and serum concentrations of the antibacterial agents were
      shown to be within nontoxic ranges. CONCLUSION: The antiseptic-impregnated
      catheters prevented bacterial adherence and biofilm formation and produced no
      local or systemic toxicity.

PMID- 7736749
TI  - Interleukin-1 receptor antagonist modifies the changes in vital organs induced by
      acute necrotizing pancreatitis in a rat experimental model.
AB  - OBJECTIVE: Interleukin-1 (IL-1) is a mediator in some critical conditions such as
      septic shock and multiple organ failure. Acute pancreatitis is one of the noted
      causes of multiple organ failure but the mechanism by which local inflammation
      progresses to systemic disease is unknown. In this study, we used an IL-1
      receptor antagonist (IL-1ra) to investigate whether multiple organ failure due to
      acute pancreatitis is mediated by IL-1, as in other causes such as severe
      infection, trauma, and major surgery. DESIGN: Prospective, randomized, controlled
      trial. SETTING: Research laboratory of a university medical school. SUBJECTS:
      Specific pathogen-free male Wistar rats weighing 200 to 250 g. INTERVENTIONS:
      Necrotizing pancreatitis was induced by retrograde injection of deoxycholate
      solution into the biliopancreatic duct. IL-1ra was injected intravenously at a
      dose of 10 mg/kg 15 mins before induction of acute pancreatitis and then infused
      continuously at a rate of 5 mg/kg/hr for the following 24 hrs. MEASUREMENTS AND
      MAIN RESULTS: Although treatment with recombinant human IL-1ra did not affect the
      degree of local pancreatic insult, it significantly reduced mortality, improved
      urine output as an indicator of the state of shock, and ameliorated the
      accumulation of neutrophils into the lung in a rat experimental pancreatitis
      model. CONCLUSIONS: We concluded that multiple organ failure in severe
      pancreatitis is mediated, at least in part, by IL-1 through the activation of
      neutrophils. Furthermore, we concluded that circulatory collapse may also be
      important in the mechanism of the lethal effect of pancreatitis.

PMID- 7736750
TI  - Effect of combined nitric oxide inhalation and NG-nitro-L-arginine infusion in
      porcine endotoxin shock.
AB  - OBJECTIVE: To evaluate the possible effects of a combination of systemic nitric
      oxide synthesis inhibition (to increase mean arterial blood pressure) and nitric
      oxide inhalation (to decrease pulmonary vascular pressure) in porcine endotoxin
      shock. DESIGN: Prospective trial. SETTING: Laboratory at a large university
      medical center. SUBJECTS: Ten pathogen-free pigs weighing 19 to 25 kg.
      INTERVENTIONS: After surgical preparation, all pigs received a continuous
      infusion of Escherichia coli lipopolysaccharide endotoxin (15 micrograms/kg/hr)
      for 2 hrs. After 1 hr of endotoxemia, nitric oxide inhalation (50 parts per
      million) and NG-nitro-L-arginine infusion (50 mg/kg/hr) were initiated in six
      pigs. Four pigs served as controls and received only a lipopolysaccharide
      infusion. MEASUREMENTS AND MAIN RESULTS: NG-nitro-L-arginine infusion and nitric
      oxide inhalation prevented the further decrease in mean arterial blood pressure
      seen in the control pigs (p < .05), but did not restore mean arterial blood
      pressure back to basal values. Cardiac output decreased significantly compared
      with controls during NG-nitro-L-arginine infusion/nitric oxide inhalation (p <
      .01). Systemic vascular resistance, which was below basal values in the controls
      after 2 hrs of endotoxemia, was markedly increased by NG-nitro-L-arginine/nitric
      oxide, to higher values than those observed in the basal state (p < .01). In the
      control pigs, mean pulmonary arterial pressure and pulmonary vascular resistance
      showed a biphasic increase. In the NG-nitro-L-arginine/nitric oxide treated
      group, the second phase increase in mean pulmonary arterial pressure did not
      occur (p < .01). However, there was no difference in pulmonary vascular
      resistance between the groups. Renal vascular resistance was unchanged in
      controls, while NG-nitro-L-arginine/nitric oxide induced a four-fold increase in
      renal vascular resistance (p < .001). There was no statistical difference in
      urine production between the groups. PaO2 values were higher and PaCO2 tensions
      were lower in the treated pigs than in the controls. Arterial pH and base excess
      did not differ. Arterial plasma epinephrine, norepinephrine, and neuropeptide Y
      concentrations increased during the lipopolysaccharide infusion in both groups,
      with a tendency toward higher concentrations in the pigs receiving NG-nitro-L
      arginine/nitric oxide. Arterial plasma endothelin-1-like immunoreactivity in
      these pigs was significantly higher at the end of the treatment than in the
      controls. CONCLUSIONS: In this model of porcine endotoxin shock, the combination
      of NG-nitro-L-arginine infusion and nitric oxide inhalation attenuated pulmonary
      hypertension and improved gas exchange; it also prevented development of further
      systemic hypotension, but impaired cardiac output and increased systemic and
      renal vascular resistances to supranormal levels. NG-nitro-L-arginine/nitric
      oxide did not reduce sympathetic nervous system activation or metabolic acidosis.

PMID- 7736751
TI  - Prolonged studies of perfluorocarbon associated gas exchange and of the
      resumption of conventional mechanical ventilation.
AB  - OBJECTIVE: To determine whether oxygenation and lung mechanics are preserved
      during perfluorocarbon associated gas exchange of 24 hrs duration and after
      evaporation of perfluorocarbon. DESIGN: Prospective, experimental animal trials.
      SETTING: Animal laboratory in a university setting. SUBJECTS: Ten normal,
      neonatal piglets weighing 2.5 to 4.5 kg. INTERVENTIONS: Ten piglets were
      anesthetized with fentanyl (25 micrograms/kg/hr), paralyzed with metocurine
      iodide (0.3 mg/kg) and placed on volume regulated continuous positive pressure
      breathing instituted at an FIO2 setting of 1.0, tidal volume of 15 mL/kg,
      respiratory rate of 25 breaths/min and positive end-expiratory pressure of 4 cm
      H2O. Perfluorocarbon associated gas exchange was initiated by intratracheal
      instillation of perflouorooctylbromide (30 mL/kg) followed by gas ventilation at
      the same settings. Evaporative losses were replaced by intratracheal instillation
      of 2.5 mL/kg/hr of perfluorocarbon. In one group of five piglets, evaporative
      losses were replaced for 24 hrs until the end of the study. In the other group of
      five piglets, replacement of perfluorocarbon was discontinued after 2 hrs,
      although gas ventilation was continued for 24 hrs. Blood gases and lung mechanics
      were measured in both groups. Histologic evaluation of lungs from both groups of
      animals was performed. MEASUREMENTS AND MAIN RESULTS: Airway pressures and blood
      gases were stable throughout the 24-hr study period in both groups. Airway
      pressures in the evaporative group increased as evaporation of perfluorocarbon
      neared completion. There was no hemodynamic deterioration during the 24-hr study
      period. Histology showed good preservation of lung architecture in both groups.
      CONCLUSIONS: Perfluorocarbon associated gas exchange was safe and effective in
      normal piglets for a period of 24 hrs. Evaporation of perfluorocarbon and
      resumption of continuous positive pressure breathing was well tolerated.

PMID- 7736752
TI  - Epinephrine-mediated changes in carbon dioxide tension during reperfusion of
      ventricular fibrillation in a canine model.
AB  - OBJECTIVE: Previous studies suggest that epinephrine may alter the correlation of
      perfusion with measures of PCO2 during cardiopulmonary resuscitation. This study
      investigated the effects of epinephrine on PaCO2 and mixed venous PCO2 in a high
      flow reperfusion model of cardiac arrest. DESIGN: Prospective, block randomized,
      blinded, placebo-controlled, laboratory study. SUBJECTS: Thirty mixed breed
      canines. INTERVENTIONS: After a 12-min ventricular fibrillation cardiac arrest,
      30 mixed breed canines were reperfused with standardized (3200 revolutions/min)
      cardiopulmonary bypass and were given placebo (n = 10), standard dose epinephrine
      (0.02 mg/kg; n = 10), or high-dose epinephrine (0.2 mg/kg; n = 10). Arterial and
      mixed venous blood gases, coronary perfusion pressure, pump flow and peripheral
      vascular resistance were compared between groups during the early reperfusion
      period using analysis of variance with a post hoc Tukey's multiple comparison
      test. MEASUREMENTS AND MAIN RESULTS: Baseline variables were similar between
      groups. With reperfusion, the high-dose epinephrine group had higher coronary
      perfusion pressures (p < .002), lower systemic pump flow (p < .01), and higher
      peripheral vascular resistance (p < .001). In the high-dose epinephrine group,
      both PaCO2 (high-dose epinephrine, 40 +/- 6 torr [5.3 +/- 0.8 kPa]; standard dose
      epinephrine, 45 +/- 7 torr [6.0 +/- 0.9 kPa]; placebo, 54 +/- 4 torr [7.2 +/- 0.5
      kPa]; p < .01) and mixed venous PCO2 (high-dose epinephrine, 55 +/- 10 torr [7.3
      +/- 1.3 kPa]; standard dose epinephrine, 57 +/- 9 torr [7.6 +/- 1.2 kPa];
      placebo, 67 +/- 4 torr [8.9 +/- 0.5 kPa]; p < .05) were significantly decreased,
      and arterial pH, PaO2, and mixed venous PO2 were significantly increased compared
      with the placebo group. CONCLUSION: In this model, when ventilation and CO2
      production are constant, the decrease in PaCO2 with epinephrine is due to
      decreased pulmonary blood flow (flow to membrane oxygenator) and peripheral
      shunting.

PMID- 7736753
TI  - Critical tissue oxygen tension defines tissue oxygen debt in the isolated
      hindlimb of the pig during progressive ischemia.
AB  - OBJECTIVE: To determine a critical skeletal muscle oxygen tension (PO2) value
      below which a tissue oxygen debt develops. DESIGN: Descriptive study of oxygen
      transport values in relation to skeletal muscle PO2 throughout progressive
      ischemia by means of arterial blood flow reductions in an isolated hindlimb model
      in the pig. SETTING: Surgical Research department of the University of Amsterdam.
      SUBJECTS: Six female Yorkshire pigs weighing 26 to 35 kg (average 33).
      INTERVENTIONS: Controlled blood flow to the isolated hindlimb was achieved by
      means of extracorporeal circulation. The hindlimb was studied during progressive
      flow reduction. MEASUREMENTS AND MAIN RESULTS: Oxygen delivery (DO2) and oxygen
      consumption were calculated as the product of extracorporeal blood flow and,
      respectively, arterial oxygen content and arterial-venous oxygen content
      difference. In this fashion, an oxygen supply dependency could be determined in
      all animals. A critical DO2 value was determined below which a tissue oxygen debt
      developed. Skeletal muscle PO2 was measured continuously, using a Clark-type
      polarographic oxygen sensor. Combining the critical DO2 value with the
      corresponding skeletal muscle PO2 value resulted in a critical skeletal muscle
      PO2 value of 15.2 +/- 0.4 torr (2.0 +/- 0.1 kPa). CONCLUSION: In this pig model,
      a critical skeletal muscle PO2 value could be determined below which a tissue
      oxygen debt presumably developed.

PMID- 7736754
TI  - Protamine does not affect the formation of cGMP or cAMP in pig vascular smooth
      muscle cells in response to vasodilators.
AB  - OBJECTIVES: Protamine has recently been shown to have a direct vasodilator action
      in isolated vascular tissue. As one possible mechanism for this action, it has
      been hypothesized that protamine might increase the response of vascular smooth
      muscle to the endothelium-derived relaxing factor, nitric oxide. In this study,
      we tested this hypothesis and examined the effect of protamine on other guanosine
      3'5'-cyclic monophosphate (cGMP)- and adenosine 3'5'-cyclic monophosphate (cAMP)
      dependent processes. DESIGN: Prospective, repeated measures analysis of
      concentration-response curves. SETTING: Anesthesia research laboratory in an
      academic medical center. SUBJECTS: Cultured coronary artery smooth muscle cells
      from pig heart. INTERVENTIONS: Sodium nitroprusside was used to mimic the action
      of the endothelium-derived relaxing factor by stimulating the soluble guanylyl
      cyclase and increasing intracellular cGMP. Atrial natriuretic peptide was used to
      stimulate the particulate guanylyl cyclase. Isoproterenol and forskolin were used
      to increase intracellular cAMP. The responses to these agents were determined in
      the presence and absence of protamine. MEASUREMENTS AND MAIN RESULTS: In cultured
      vascular smooth muscle cells, sodium nitroprusside increased cGMP, the second
      messenger for endothelium-derived relaxing factor, in a concentration-dependent
      manner. In cells treated with protamine (32 to 250 micrograms/mL), we could
      detect no effect of protamine on basal intracellular levels of cGMP until a
      concentration of 250 micrograms/mL of protamine was used. At this concentration,
      protamine increased basal cGMP concentrations from 4.2 +/- 0.3 to 9.0 +/- 0.6
      pmol/mg protein (p < .001). The response of intracellular cGMP to sodium
      nitroprusside in cells treated with 250 micrograms/mL or other concentrations of
      protamine was not different from control. Likewise, we could detect no effect of
      protamine on intracellular cGMP stimulated with the atrial natriuretic peptide or
      on cAMP stimulated with the beta-adrenergic receptor agonist, isoproterenol, or
      with forskolin. CONCLUSIONS: These experiments show that protamine does not alter
      the responses of the intracellular second messengers, cGMP and cAMP, to the
      vasodilators sodium nitroprusside, atrial natriuretic peptide, isoproterenol, and
      forskolin. These results do not support the hypothesis that protamine sensitizes
      vascular smooth muscle cells to the endothelium-derived relaxing factor, nitric
      oxide.

PMID- 7736755
TI  - Continuous versus bolus thermodilution cardiac output measurements--a comparative
      study.
AB  - OBJECTIVE: To compare the methods for continuous and bolus thermodilution cardiac
      output measurements. DESIGN: In vivo and in vitro experimental studies. SETTING:
      Surgical research division in a university hospital. SUBJECTS: Eight calves and
      flow bench model. INTERVENTIONS: Data were collected in vivo from eight calves
      instrumented with pulmonary artery catheters, which allowed both continuous and
      bolus thermodilution measurements. The pulmonary artery catheter was placed
      through the external jugular vein. All in vitro measurements were performed using
      a flow bench model. MEASUREMENTS AND MAIN RESULTS: A total of 232 bolus and
      continuous thermodilution measurements were analysed in vivo to determine the
      degree of agreement between the two methods. The absolute measurement bias was
      0.14 L/min with 95% confidence limits ranging from -0.83 to 1.15 L/min. In vitro
      analysis of 576 measurements at six different temperature points (range 31
      degrees to 41 degrees C), using clinically relevant flows (2 to 9 L/min), showed
      overestimation of flow values using continuous and bolus thermodilution methods.
      However, the continuous method showed better accuracy by a lower degree of
      overestimation. Systematic error was 9.7 +/- 8.4 (SD) % for continuous and 11.1
      +/- 6.3% for the bolus method (p < .001). This effect was especially evident at
      lower flow rates. The influence of various temperatures on the accuracy and
      reproducibility of both methods of measurement was statistically significant but
      not clinically relevant. The infusion of lactated Ringer's lactate solution
      (infusion rates 100 to 1000 mL/hr) affects both methods at a low flow rate of 2
      L/min, without causing a significant effect on continuous measurement at a higher
      flow rate (4 L/min). Shunting of 50% of circulating volume to the distal part of
      the thermal filament of the pulmonary catheter impaired the accuracy of
      continuous measurement without affecting results from bolus measurements
      (systematic error -26.8 +/- 8.2% for continuous and -5.2 +/- 4.1% for bolus
      thermodilution). CONCLUSIONS: Continuous thermodilution cardiac output
      measurement provided higher accuracy and greater resistance to thermal noise than
      standard bolus measurements. The correct placement of the catheter is essential
      for precise measurements.

PMID- 7736756
TI  - Validation and comparison of models predicting survival following intracerebral
      hemorrhage.
AB  - OBJECTIVE: To compare the performance of two previously reported logistic
      regression models using data independent from those data used to derive the
      models. DESIGN: Prospective. SETTING: Acute stroke unit of a tertiary care
      hospital. PATIENTS: One hundred twenty-nine patients with supratentorial
      intracerebral hemorrhage. MEASUREMENTS AND MAIN RESULTS: Model 1 contains the
      initial Glasgow Coma Scale score, hemorrhage size, and pulse pressure. The more
      complex model 2 includes, in addition to those three variables, the presence or
      absence of intraventricular hemorrhage and a term representing the interaction of
      intraventricular hemorrhage and Glasgow Coma Scale score. The areas under the
      receiver operating characteristic curves generated for each model were
      statistically indistinguishable. CONCLUSIONS: Model 1 predicts 30-day patient
      status as well as the more complex model 2. Model 1 provides a valid, easy-to-use
      means of categorizing supratentorial intracerebral hemorrhage patients in terms
      of their probability of survival.

PMID- 7736757
TI  - Strategies for blocking the systemic effects of cytokines in the sepsis syndrome.
AB  - OBJECTIVES: To review and evaluate animal and human data regarding strategies to
      intervene in the pathogenesis of the sepsis syndrome by specifically blocking the
      action of single cytokines. DATA SOURCES: The English language medical literature
      was reviewed, including reports of human clinical trials, animal experiments, and
      in vitro studies elucidating cellular and molecular interactions. STUDY
      SELECTION: Emphasis was placed on controlled experimental studies that elucidated
      the effectiveness of antibodies, soluble receptors, and receptor antagonists in
      intervening in the pathogenesis of the sepsis reaction. DATA EXTRACTION: This
      review focuses on data that directly involve the induction and regulation of
      protein mediators of sepsis, especially tumor necrosis factor-alpha, interleukin
      1 beta, interleukin-6, and interleukin-8. DATA SYNTHESIS: Information concerning
      the potential of cytokine blockers in modulating the sepsis reaction is presented
      in a logical, clinically oriented fashion. The purpose is to emphasize the
      potential role of these agents by focusing on the actual existing data.
      CONCLUSIONS: The pathophysiology of the sepsis reaction appears to involve the
      sequential release of cytokines. Interventions designed to specifically block the
      biological effects of single cytokines appear to have a role in the management of
      sepsis syndrome, but well-designed, prospective, randomized, placebo-controlled
      clinical trials in well-defined clinical populations are necessary to define this
      role. These trials require the cooperation of clinical and basic scientists.

PMID- 7736758
TI  - A review of cost studies of intensive care units: problems with the cost concept.
AB  - OBJECTIVE: To study methods for costing hospital services, specifically in
      relation to multi-unit studies of activity, case mix, severity of illness,
      outcome, and resource use in adult intensive care units (ICUs). DATA SOURCES:
      Twenty published cost studies of adult ICUs. The studies are all published in
      English and are both European and American. STUDY SELECTION: Cost studies of
      adult ICUs published in international journals (English language). DATA
      EXTRACTION: Literature survey, where the articles were obtained through MEDLINE
      and other database searches. DATA SYNTHESIS: Cost of intensive care therapy was
      compared across the 20 studies. However, as stressed in the article, to compare
      costs of intensive care therapy across units is not possible for a number of
      reasons. One of the reasons for this limitation is that the studies employed
      different approaches to costing and thereby introduced a methodologic bias. In
      addition, the costing methodology applied in the majority of the studies was
      wrongly specified in relation to the purpose and viewpoint of the studies.
      CONCLUSIONS: The methodologies for costing ICU therapy are flawed and fail to
      provide correct answers. In most studies, the study question is not adequately
      specified and the cost concept used in the studies is not tailored to the
      purposes of the study. Standardizing the cost model would lead to better, faster,
      and more reliable costing. This standardized cost model should not be rigid, but
      adaptable to different decision situations. A decision tree or taxonomy is
      proposed as a way toward better costing of ICU activity.

PMID- 7736759
TI  - Increased serum cytokines and intercellular adhesion molecule-1 in fulminant
      Rocky Mountain spotted fever.

PMID- 7736760
TI  - Fatal amrinone overdose in a pediatric patient.

PMID- 7736761
TI  - Heat shock response in sepsis.

PMID- 7736762
TI  - Continuous hemofiltration and platelet function.

PMID- 7736763
TI  - Continuous hemofiltration and platelet function.

PMID- 7736764
TI  - Endotoxin-neutralizing protein.

PMID- 7736765
TI  - Hyperventilation with increased intracranial pressure.

PMID- 7736766
TI  - X-ray scanning microanalysis of Sporothrix schenckii.
AB  - X-ray scanning microanalysis was applied to the study of fungal samples such as
      Sporothrix schenckii. This technique is sufficiently sensitive to detect many
      elements in the periodical classification of Mendeleev.

PMID- 7736767
TI  - Ultrastructural evidence for the presence of crystalline structures in pig
      vaginal epithelial cells.
AB  - Terminally differentiated intermediate layers of vaginal epithelial cells from
      the late follicular phase of the pig show crystalline structures. Analysis of two
      dimensional images by transmission electron microscopy revealed that these
      structures are composed of rhomboid subunits. The longer side measures 26 nm
      whereas the smaller side measures 24 nm. The angles between the sides are 100
      degrees and 80 degrees. These structures are not associated with any cellular
      structures and are not evident in other phases of the oestrous cycle.
      Structurally, they do not match with Reinke's crystals and are probably regulated
      by hormones.

PMID- 7736768
TI  - Changes of 3H-thymidine incorporation into DNA and thymidine kinase activity in
      rat thyroid lobes, following their exposure to neuropeptide Y.
AB  - The effects of neuropeptide Y (NPY) on 3H-thymidine incorporation into DNA of rat
      thyroid lobes in a 4 h incubation, and on the activity of thymidine kinase (TK)
      in the homogenates of thyroid lobes in vitro, as well as the influence of
      thyrotropin (TSH), applied alone or together with NPY, were investigated. The
      effects of NPY were dependent on the concentration used. Neuropeptide Y, in the
      lowest and the highest concentrations, decreased both the incorporation of 3H
      thymidine to DNA and TK activity, and when used in intermediate concentrations
      NPY did not significantly affect the processes examined. Thyrotropin decreased TK
      activity and revealed a tendency towards lowering 3H-thymidine uptake, the latter
      effect being not statistically significant. NPY (10(-10) M) used together with
      TSH, produced an increase of 3H-thymidine incorporation into DNA, when compared
      with controls and the TSH-exposed group. Following the joint exposure to NPY and
      TSH, TK activity declined.

PMID- 7736769
TI  - The acceleration of pH volume changes in human red cells by bicarbonate and the
      role of carbonic anhydrase.
AB  - The red cell shrinkage rate due to bicarbonate in media of high pH (ca 9.4) has
      been compared with the hydroxyl shrinkage rate on a per mM basis. The shrinkage
      rate due to bicarbonate was only half that due to OH-/Cl- exchanges. It was
      therefore deduced that the Jacobs-Stewart cycle was limited by the carbonic
      anhydrase step and not by the rate of transport on the anion exchanger protein.
      To explain this and other anomalies the hypothesis is made that carbonic
      anhydrase has evolved as a pH-dependent catalyst with specific physiological
      functions in pH regulation and in other cellular mechanisms. The kinetic theory
      and some physiological implications of the hypothesis are discussed.

PMID- 7736770
TI  - Genome DNA analysis and genotyping of clinical isolates of Helicobacter pylori.
AB  - The genotype of genome DNA from seventeen clinical isolates of Helicobacter
      pylori by pulsed-field gel electrophoresis (PFGE) and arbitrarily primed
      polymerase chain reaction (AP-PCR) was determined. Three restriction enzymes, Apa
      I, Kpn I and Not I, were found to produce distributions of DNA fragments which
      were useful for analysis of the chromosome-sized DNA from H. pylori NCTC11637T by
      PFGE. Many of the isolates of H. pylori could not be genotyped by PFGE after
      digestion reaction with Apa I, Kpn I, and Not I. When AP-PCR with a ten
      nucleotide primer was performed using the chromosomal genomic DNA from the
      isolates as templates, fifteen distinctly different profiles were obtained from
      the seventeen isolates. Thus, genotyping of the isolates was possible where PFGE
      profiles had not previously been informative. The results suggest that AP-PCR is
      more suitable for genotyping of clinical isolates of H. pylori in Japan than
      PFGE.

PMID- 7736771
TI  - Report and abstracts of the Second International Workshop on Human Chromosome 13
      Mapping 1994.

PMID- 7736772
TI  - Regional localisation of tri- and tetranucleotide repeat sequence-containing
      cosmids on chromosome 13.
AB  - A human chromosome 13-specific cosmid library has been screened with
      oligonucleotides containing tri- and tetranucleotide repeats with motifs: GACA,
      GACT, CAC, TCC. 20 cosmid clones were identified and their physical location on
      chromosome 13 was determined using fluorescence in situ hybridisation. Over 80%
      of the cosmids were detected using tetranucleotide repeats of which 50% were
      GACT, but these were distributed along the length of the chromosome. Clones from
      the 13q12-->q14 and 13q32-->q34 regions were apparently overrepresented and 10%
      of cosmids were localised to the short arm of the chromosome. These simple tandem
      repeats will be an important addition to the genetic mapping strategy for human
      chromosome 13.

PMID- 7736773
TI  - Fifty novel sequence-tagged sites (STSs) on human chromosome 11q13.4-->q25
      identified from microclones generated by microdissection.
AB  - Fifty sequence-tagged sites (STSs) from human chromosome region, 11q13.4-->q25
      were identified in microdissection-generated microclones. From a total of 124
      single-copy microclones obtained from regions 11q14-->q22 and 11q23-->q25, 59
      were sequenced, and a PCR primer pair was designed for each of them. Fifty of the
      59 clones were mapped to regions ranging from 11q13.4 to 11q25 by means of PCR on
      a somatic hybrid cell panel with various deletions of the long arm of human
      chromosome 11. These STSs will contribute to the construction of physical
      cosmid/YAC maps representing the chromosome regions. They are also useful for
      analysis of chromosome aberrations, such as translocations, inversions or marker
      chromosomes.

PMID- 7736774
TI  - Evolutionary conservation of a microsatellite in the Wilms tumour (WT) gene:
      mapping in sheep and cattle.
AB  - A microsatellite in the WT (Wilms tumour) gene is shown to be evolutionarily
      conserved in a range of mammals. The microsatellite was monomorphic in pig and
      two alleles have been found in goat. In cattle, a one-base size polymorphism has
      been discovered outside the microsatellite. WT was genetically mapped to bovine
      chromosome 15 and to sheep chromosome 15 by synteny mapping. Conservation of
      chromosome segments of HSA11 and BTA15 is discussed.

PMID- 7736775
TI  - Regional localization of the ovine NRAMP gene to chromosome 2q41-->q42 by in situ
      hybridization.
AB  - The murine Ity/Lsh/Bcg locus belongs to a conserved region between mouse
      Chromosome 1 and human chromosome 2. This gene governs mouse resistance to
      several intracellular pathogens. We have localized the gene on sheep chromosome
      2q41-->q42 by radioactive in situ hybridization using a 2.1-kb fragment of the
      ovine equivalent of this gene.

PMID- 7736776
TI  - The small cell lung cancer antigen cluster-4 and the leukocyte antigen CD24 are
      allelic isoforms of the same gene (CD24) on chromosome band 6q21.
AB  - Cluster-4 and CD24 cDNA's have recently been cloned from the small cell lung
      carcinoma (SCLC) cell line SW2 and from the erythroleukemia cell line K562,
      respectively. The only difference in the coding sequence, between cluster-4 and
      CD24 antigens is the substitution of a single base pair leading to a substitution
      of Val by Ala near the putative glycosylphosphatidylinositol (GPI) anchorage
      sites of the mature protein. Here we demonstrate that the nucleotide substitution
      which distinguishes the cluster-4 and CD24 antigen genes is due to an allelic
      polymorphism on chromosome band 6q21. In addition, we identified by Southern
      blotting and PCR of DNA from somatic human x hamster hybrid cell lines homologues
      of cluster-4/CD24 on the Y chromosome and chromosome 15. We suggest, however,
      that the gene on 6q21 is the active locus since the mRNA of cell lines always
      represents the allelic variants found on chromosome 6. The distribution pattern
      of this allelic polymorphism in SCLC cell lines and leukocytes of healthy donors
      did not reveal any obvious relationship with disease. However, it is noteworthy
      that homozygosity for cluster-4 was found in only one case whereas heterozygosity
      and homozygosity for CD24 both contribute up to 50% of the samples examined.

PMID- 7736777
TI  - The lymphoid proliferation-associated gene EPAG maps to human chromosome region
      Xq21-->q22.
AB  - Using Southern blot and fluorescence in situ hybridization analyses, we have
      shown that the novel human gene EPAG, expressed in association with the mitogenic
      activation of T and B cells in peripheral blood, maps to chromosome region Xq21-
      >q22. These data establish EPAG as a candidate gene in X-linked disorders.

PMID- 7736778
TI  - Precise ordering of 26 cosmid markers on chromosome region 3p23-->p21.3 by two
      color FISH on human prophase chromosomes and stretched DNAs.
AB  - To construct a detailed cytogenetic map of human chromosome region 3p23-->p21.3,
      we determined the order of 26 cosmid markers (cCI 3 series) previously localized
      within this region by fluorescence in situ hybridization (FISH). Two-color
      pairwise FISH analysis of prophase chromosomes provided the order of these
      markers as follows: pter - 245 (D3S647) - 872 (D3S1018) - 818 (D3S996) - 905
      (D3S1022) - 515 (D3S685) - 1195 (D3S1125) - 718 (D3S935) - 911 (D3S1025) - 878
      (D3S1020) - 717 (D3S934) - 401 (D3S664) - [708 (D3S926)/524 (D3S686)] - 848
      (D3S1011) - 771 (D3S966) - 917 (D3S1029) - 533 (D3S688) - 470 (D3S676) - 940
      (D3S1037) - 785 (D3S974) - 810 (D3S988) - 9 (D3S643) - 382 (D3S660) - 769
      (D3S965) - 792 (D3S978) - 604 (D3S705) - cen. The two-color signals of 524
      (D3S686) and 708 (D3S926) were visualized as an overlapping pattern on prophase
      chromosomes, and, further, the string signals also overlapped on stretched DNAs,
      allowing us to determine their precise order as pter - D3S926 - D3S686 - cen. The
      precise order of 26 DNA markers on 3p23-->p21.3 can provide useful information
      for the positional cloning of tumor suppressor gene(s) and cancer breakpoint(s)
      encompassed in this region.

PMID- 7736779
TI  - Selection of chromosome-specific primers and their use in simple and double PRINS
      techniques for rapid in situ identification of human chromosomes.
AB  - The PRimed IN Situ labeling (PRINS) technique is an alternative to in situ
      hybridization for rapid chromosome screening. We have defined and tested new
      specific oligonucleotide primers for alpha-satellite DNA of several chromosomes.
      When using a semiautomatic PRINS protocol, specific labeling was obtained in both
      metaphase cells and interphase nuclei in a 1-h reaction. PRINS may be a simple
      and reliable technique for rapidly detecting aneuploidies.

PMID- 7736780
TI  - Localization of the murine homolog of the anaplastic lymphoma kinase (AlK) gene
      on mouse chromosome 17.
AB  - The murine homolog of the human anaplastic lymphoma kinase gene, which encodes a
      membrane-spanning receptor tyrosine kinase in the insulin receptor kinase
      subfamily, was assigned to mouse Chromosome 17 by interspecific backcross
      analysis. This assignment further confirms the homology between a portion of the
      distal Chromosome 17 and the short arm of human chromosome 2 and extends this
      region in the mouse by an additional 3 cM.

PMID- 7736781
TI  - The kinase insert domain receptor gene (KDR) has been relocated to chromosome
      4q11-->q12.
AB  - Through in situ hybridization of a genomic DNA probe to metaphase chromosomes, we
      have localized the KDR gene to 4q11-->q12. This is the same locus as that for two
      other receptor tyrosine kinases, PDGFRA and KIT. This location for KDR differs
      from that which we previously reported using a cDNA probe. Using cDNA probes for
      both KDR and KIT identifies a locus at 4q31-->q32 which may uncover another
      cluster of receptor tyrosine kinase genes.

PMID- 7736782
TI  - Subregional localization of 14 yeast artificial chromosomes to human chromosome
      region 1p by fluorescence in situ hybridization.
AB  - We have sublocalized to the region between 1p22 and 1p33 a total of 14 yeast
      artificial chromosomes previously assigned to a broader area of human chromosome
      1p. Our purpose was to map DNA sequences that could be used for the molecular
      characterization of the two common fragile sites present in bands 1p31.2 and
      1p32, the expression of which is increased in patients with neuroblastomas.

PMID- 7736783
TI  - Three members of the human cystatin gene superfamily, AHSG, HRG, and KNG, map
      within one megabase of genomic DNA at 3q27.
AB  - While constructing a contig in the human chromosome region 3q27, we identified
      two YAC clones that were positive for the polymorphic marker D3S1602. One of
      these clones was also positive for a sequence-tagged site derived from the
      kininogen (KNG) gene. Because of the known evolutionary and structural
      relationship of KNG to other members of the cystatin gene superfamily, we tested
      the physical linkage of the genes encoding alpha-2HS-glycoprotein (AHSG), KNG,
      and histidine-rich glycoprotein (HRG), all of which were previously mapped to the
      long arm of chromosome 3. Our results show the colocalization of the three genes
      in two independent, partially overlapping YAC clones. The genomic inserts of the
      two clones were 1 Mb and 1.3 Mb in size, indicating that the three genes map
      within 1 Mb of DNA. The largest YAC was also positive for the polymorphic marker
      D3S1262, substantiating previously reported data of genetic linkage between this
      marker and HRG. Fluorescence in situ hybridization localized the two YAC clones
      to chromosome band 3q27.

PMID- 7736784
TI  - Chromosome banding patterns in the unisexual microteiid Gymnophthalmus underwoodi
      and in two related sibling species (Gymnophthalmidae, Sauria).
AB  - Cytogenetic investigation of three species of the genus Gymnophthalmus (the
      unisexual G. underwoodi, G. leucomystax and Gymnophthalmus sp.n., a new,
      undescribed red-tailed species) documented three different karyotypes, all with
      2n = 44. Chromosomes from fibroblast cultures were studied after routine Giemsa
      staining, CBG-banding, RBG-banding, and Ag-NOR staining. The unisexual species
      showed a very distinctive karyotype from the one previously described that,
      paradoxically, corresponded to the predicted karyotype of one of its parental
      species. Our chromosome data unequivocally show that there are two
      parthenogenetic species with two different mechanisms of origin under the name
      underwoodi.

PMID- 7736785
TI  - Direct microdissection and microcloning of a translocation breakpoint region,
      t(1;11)(q42.2;q21), associated with schizophrenia.
AB  - We describe the generation of large-fragment microclone libraries from the
      chromosomal breakpoint of a reciprocal balanced translocation linked to
      schizophrenia. The abnormality was visible under the phase-contrast microscope,
      allowing direct dissection from unstained, unbanded metaphases. Two separate
      microdissection experiments yielded 443 and 672 recombinants, respectively.
      Following complete EcoRI digestion, inserts with an average size of 0.3 kb
      (range, 0.2-3 kb) were obtained in the first experiment and 1.5 kb (range, 0.15
      6.5 kb) in the second. FISH analysis of pooled clones "painted" back onto the
      derivative chromosome and assignment of microclones to somatic cell hybrids
      confirmed the fidelity of the method. Microdissection of chromosome regions
      identified by karyotype rearrangements in unstained, unbanded metaphases is a
      potentially powerful tool for positional cloning.

PMID- 7736786
TI  - Human origin of micronuclei in human x hamster two-cell embryos.
AB  - Using fluorescence in situ hybridization techniques with either human or hamster
      genomic DNA probes, we studied the origin of micronuclei in two-cell hybrid
      embryos obtained from hamster oocytes and gamma-irradiated human spermatozoa. Our
      study demonstrates that over 99% of micronuclei hybridize with human DNA probes
      and not with hamster DNA, revealing their human origin. Thus, the micronucleus
      test represents a good method to evaluate genetic damage in human germ cells,
      since it is simpler and faster than sperm chromosome studies.

PMID- 7736787
TI  - Dehydroepiandrosterone sulfotransferase gene (STD): localization to human
      chromosome band 19q13.3.
AB  - Dehydroepiandrosterone (DHEA) sulfotransferase (ST) catalyzes the sulfate
      conjugation of DHEA and other steroid compounds. The human gene for DHEA ST (STD)
      was mapped by the polymerase chain reaction to chromosome 19 using human x rodent
      somatic cell hybrid panels. Fluorescence in situ hybridization was then used to
      localize the STD gene to the region 19q13.3.

PMID- 7736788
TI  - The invasion-inducing TIAM1 gene maps to human chromosome band 21q22 and mouse
      chromosome 16.
AB  - The murine invasion-inducing Tiam1 gene maps to the distal end of chromosome 16,
      3.8 cM centromeric of the Ets2 gene. TIAM1, the human homolog of Tiam1, maps to
      the syntenic region (q22) on human chromosome 21. The gene order in 21q22 is cen
      TIAM1-AML1-ERG-ETS2-tel.

PMID- 7736789
TI  - Assignment of the human protein tyrosine phosphatase, receptor-type, zeta (PTPRZ)
      gene to chromosome band 7q31.3.
AB  - Human protein tyrosine phosphatase, receptor-type, zeta (PTPRZ; also denoted HPTP
      zeta or RPTP beta) has a large extracellular region with the N-terminal carbonic
      anhydrase-like domain and a cytoplasmic region with two tandemly located protein
      tyrosine phosphatase domains. One of the characteristics of PTPRZ is its
      preferential expression in the central nervous system. We localized the human
      PTPRZ gene to chromosome band 7q31.3 by somatic cell hybrid mapping and
      fluorescence in situ hybridization.

PMID- 7736790
TI  - Comparative mapping of the gene encoding the catalytic subunit of protein
      phosphatase type 1 alpha (PPP1CA) to human, rat, and mouse chromosomes.
AB  - Using fluorescence in situ hybridization method, the gene encoding the protein
      phosphatase type 1 alpha catalytic subunit (PPP1CA) was localized to human
      chromosome band 11q13, rat chromosome band 1q43, and mouse chromosome band 7E3
      F2. These results suggest that PPP1CA is a member of a syntenic group.

PMID- 7736791
TI  - Two categories of synovial sarcoma defined by divergent chromosome translocation
      breakpoints in Xp11.2, with implications for the histologic sub-classification of
      synovial sarcoma.
AB  - Molecular analysis of a new series of synovial sarcomas confirms that
      t(X;18)(p11.2;q11.2) breakpoints occur at two distinct regions on Xp designated
      SS1 and SS2. Breakpoint position correlates with tumor phenotype. Monophasic
      tumors with no evidence of glandular components have breakpoints within the SS2
      region in Xp11.21, and biphasic tumors with a focal poorly differentiated or
      extensive glandular structure have breakpoints within the SS1 region in Xp11.23.

PMID- 7736792
TI  - Human gp130 transducer chain gene (IL6ST) is localized to chromosome band 5q11
      and possesses a pseudogene on chromosome band 17p11.
AB  - Human gp130 (IL6ST) is one of the most widely used chains of the cytokine
      receptor family. Indeed, it is involved in signal transduction of interleukin-6,
      interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary
      neurotrophic factor. In a previous report, IL6ST was assigned to chromosomes 5
      and 17. Here we specify the chromosomal sublocalization of IL6ST and show that
      the sequence detected on 17p11 corresponds, in fact, to a nontranscribed
      pseudogene, whereas the active gene is located at chromosome band 5q11.

PMID- 7736793
TI  - Assignment of the human beta-catenin gene (CTNNB1) to 3p22-->p21.3 by
      fluorescence in situ hybridization.
AB  - The human beta-catenin gene (CTNNB1) has been localized to 3p22-->p21.3 by
      fluorescence in situ hybridization. Recent studies have suggested the presence of
      one or more tumor suppressor genes on the short arm of chromosome 3. This raises
      the possibility that CTNNB1, for which important features are already known, is
      involved in tumor progression.

PMID- 7736794
TI  - Regional localisation of 19 brain expressed sequence tags to human chromosome 11
      using PCR amplification of somatic cell hybrid DNAs.
AB  - Expressed sequence tags (ESTs) provide an efficient route to the identification
      of genes involved in normal development and in disease. PCR amplification of
      somatic cell hybrid DNAs was used to localise 22 brain-derived ESTs to subregions
      of human chromosome 11. Problems encountered with the standardised PCR conditions
      were overcome by optimising the annealing temperatures and the use of "touchdown"
      PCR. Amplification of the correct target sequence allowed the mapping of 19 ESTs,
      8 to the short arm and 11 to the long arm of chromosome 11. No definitive
      localisation could be determined for the three remaining ESTs.

PMID- 7736795
TI  - Additional assignment of the human 5S rRNA genes to chromosome region 1q31.
AB  - A major fraction of the human 5S rRNA genes has previously been assigned to
      chromosome region 1q42.11-->q42.13 (Sorensen et al., 1991). Through in situ
      hybridization of different tritiated probes to metaphase spreads, we have
      demonstrated that a minor fraction of the 5S rRNA genes is localized at band
      1q31. This fraction amounts to 25-30% of the genes found in the region 1q42.11-
      >q42.13. Results obtained with the chromosomes of a balanced translocation
      carrier involving this region indicate that the major cluster is localized in
      band 1q42.13.

PMID- 7736796
TI  - Segregation analysis of four translocations, t(2;18), t(3;15), t(5;7), and
      t(10;12), by sperm chromosome studies and a review of the literature.
AB  - We examined the meiotic segregation patterns of 444 sperm cells belonging to four
      reciprocal translocation carriers, t(2;18)(p21;q11.2), t(3;15)(q26.2; q26.1),
      t(5;7)(q13; p15.1), and t(10;12)(q26.1;p13.3). For the t(2;18) carrier, the
      frequencies of alternate, adjacent-1, adjacent-2, and 3:1 segregations were
      41.9%, 35.2%, 14.4%, and 8.4%, respectively. For the t(3;15) carrier, the
      segregation pattern was 48% alternate, 36% adjacent-1, 12% adjacent-2, 2% 3:1,
      and 2% 4:0. One cell was the result of a 4:0 segregation. For the t(5;7)
      heterozygote, the corresponding segregation frequencies were 40.2%, 26.2%, 16.6%,
      and 17.0%. This translocation heterozygote showed a higher number of 3:1
      segregations than adjacent-2 segregations, which is unusual. The t(10;12)
      segregations were 61.1%, 26.3%, 6.9%, and 5.6%. The percentages of chromosome
      abnormalities unrelated to the translocation ranged from 0% to 0.6% for
      aneuploidy and from 5.5% to 10.9% for structural abnormalities. These frequencies
      are within the ranges for control donors. Sperm chromosome data from the
      literature on the segregation of 30 reciprocal translocations were reviewed.

PMID- 7736797
TI  - A human 12p-derived cosmid hybridizing to subsets of human and chimpanzee
      telomeres.
AB  - The chromosomal locations of a cosmid-linking clone, cLN12-43, isolated from band
      12p13 in man and containing subtelomeric repeat sequences, were determined by
      FISH. The cosmid hybridized to the telomeres of 3q, 6p, 9p, 12p, 15q, 19p, 20p,
      and 20q at high frequency and showed variable hybridization to 1p, 6q, and 9q.
      Two interstitial loci were detected, one at bands 2q13-->q14 and the other at
      band 12q13. The former corresponds to the fusion point of chimpanzee chromosomes
      12 and 13, resulting in the human chromosome 2, whereas the latter may represent
      a similar but more ancient fusion event. The cLN12-43 cosmid was also shown to
      hybridize to a set of chimpanzee telomeres.

PMID- 7736798
TI  - A microdissection library of the rat renal carcinoma gene region.
AB  - Predisposition to hereditary renal carcinoma in the Eker rat involves a mutation
      of a putative tumor suppressor gene within chromosome band 10q12. We describe the
      identification of three unique polymorphic sequences in the vicinity of this
      locus following the microdissection, construction and characterization of a
      region-specific DNA library for rat chromosome band 10q12.

PMID- 7736799
TI  - Construction of Chinese hamster chromosome specific DNA libraries and their use
      in the analysis of spontaneous chromosome rearrangements in different cell lines.
AB  - Chinese hamster (Cricetulus griseus) and a wide variety of cell lines derived
      from it have been extensively used for radiobiological and genotoxicity studies.
      In this report, we describe the development of chromosome-specific DNA libraries
      for Chinese hamster chromosomes 1, 2, 3, 5, 6, 7 and 8 by the linker/adaptor
      method. The specificity of these probes have been checked by FISH on primary
      embryonic fibroblast (CHE) metaphase chromosomes. The diploid number of
      chromosomes in different cell lines of CHO often varies from 19 to 21 and
      karyotyping is very difficult owing to many spontaneous rearrangements. Using
      Chinese hamster chromosome-specific DNA libraries, we have analysed the
      spontaneous chromosome rearrangements in three different Chinese hamster
      transformed cell lines, V79, CHO-KI and CHO-9. The results indicate that one of
      each of the first and fifth pair of chromosomes are involved in reciprocal
      translocations in both CHO-9 and CHO-K1 cells. The hybridisation patterns
      obtained with chromosome-specific probes 2, 3, 5, 6, 7 and 8 indicated
      rearrangements have occurred involving terminal and interstitial translocations
      in V79, CHO-KI and CHO-9 cells.

PMID- 7736800
TI  - International adoption: a case review of Korean children.
AB  - In contrast to the controversial transracial adoption of African American
      children by Caucasian families in the U.S., international, transracial adoption
      of Asian children has not received much scientific or societal attention. There
      has been a steady increase in this unnoticed minority group, made up largely of
      Korean children. This paper reviews the developmental characteristics of post
      adoption adjustments among Korean adoptees and discusses the dynamics of their
      positive adjustments. Sociopolitical issues of international adoptions are also
      addressed.

PMID- 7736801
TI  - Welfare reform: a commentary.
AB  - Aid to the Families of Dependent Children (AFDC) has been successful in most
      cases. Welfare reform should focus on aiding children by identifying and helping
      dysfunctional, welfare dependent parents when possible and relieving them of
      parenting responsibilities with adoption of their children when they neglect and
      abuse their children and are unable or unwilling to become competent parents.
      AFDC is illsuited to be an employment or an antipoverty program.

PMID- 7736802
TI  - Interpreting the effects of mothers' postnatal depression on children's
      intelligence: a critique and re-analysis.
AB  - It is possible that reported links between postnatal depression and children's
      cognitive deficits can be completely explained by vulnerability factors in the
      child such as male gender and pre- and perinatal insults as well as known risk
      factors in the social environment. This hypothesis was evaluated, using
      prospective longitudinal data that had previously been obtained from a community
      sample of primiparous North London women, followed from early pregnancy until the
      children were 4 years old. Re-analysis of those data provided support for the
      original finding of an association between postnatal depression and impaired
      cognitive abilities in the children. There were, however, some important
      modifications: Low birth-weight infants and the infants of less educated mothers
      were most at risk. Perceptual and performance abilities were most affected.

PMID- 7736803
TI  - Behavior of conduct disordered children in interaction with each other and with
      normal peers.
AB  - This study investigated the behavior of children with conduct disorder or
      oppositional defiant disorder (CD/ODD) in interaction with each other and with
      normal control (NC) children in a semi-standardized setting over a period of 25
      minutes. This short time turned out to be sufficient to demonstrate the
      behavioral manifestations of CD/ODD in children's interactions with peers. In
      addition, the role of the interactional partner on antisocial behaviour of CD/ODD
      children became apparent.

PMID- 7736804
TI  - Prediction and constancy of cognitive-motivational structures in mothers and
      their adolescents.
AB  - Three clinically-derived, cognitive-motivational structures were predicted in 68
      adolescents from their caregiving situations as revealed in their mothers'
      interviews, elicited six years earlier. Basic to each structure is a motivational
      concern and its related social cognitive style, a style which corresponds to a
      Piagetian cognitive stage: concrete operational, intuitive or symbolic. Because
      these structure types parse a non-clinical population, current views of health
      and accordingly goals of treatment may need modification.

PMID- 7736805
TI  - [Studies on the possibility of using lyophilized in vitro autogenic bone marrow
      derived stromal cells to stimulate healing of bone lesions in the jaws].
AB  - The authors describe a new method of stimulation of regeneration of bone tissue
      using autografts of autologous bone marrow supplemented with autologous bone
      marrow stromal fibroblastoid cells (with osteogenic potential) grown in vitro and
      lyophilized allogenic bone. Such composite grafts have been used in the treatment
      of 10 patients with lesion in jaw bone. Bone healing was evaluated using clinical
      and radiological parameters and was compared with healing in 30 similar lesions
      treated using composite grafts of autologous bone marrow and allogenic
      lyophilized bone as well as the spontaneous healing of 45 post-cystic lesions.
      These data indicate, that composite grafts of autologous bone marrow supplemented
      with in vitro grown autologous bone marrow stromal cells and lyophilized
      allogenic bone have excellent capacities accelerating bone healing. In smaller
      lesions, composite grafts of fresh autologous bone marrow and allogenic
      lyophilized bone (which are easier to prepare) are also useful.

PMID- 7736806
TI  - [Diagnostic significance of percutaneous needle biopsy in metastatic neoplasms of
      the spine].
AB  - A retrospective review of percutaneous needle biopsy due to the vertebral
      metastatic neoplasms performed in 92 patients treated from 1975 to 1992 at
      Department of Neurosurgery, K. Marcinkowski University of Medical Sciences.
      Thoracic biopsies constituted 45 per cent, lumbar-32 per cent, cervical-18 per
      cent and sacral ones 5 per cent of all procedures. An accurate diagnosis was made
      in 70 per cent of all cases. The highest accuracy rate was noted in lesions
      compromising the entire vertebral body (84 per cent) and posterior elements of
      the vertebrae (89 per cent). Tomographic X-rays, CT and MRI were helpful in
      visualization of concomitant paravertebral mass. In these cases accuracy rate of
      the biopsy was 82 per cent. The technique of percutaneous biopsy and histological
      results were also discussed.

PMID- 7736807
TI  - [Sequelae of septic arthritis of the hip in newborns].
AB  - The sequelae of arthritis of the hip in neonatal period have been analyzed in a
      series of 75 hips in 68 patients aged from 2 months to 14 years. The diagnosis
      was set on the basis of history, medical documentation, clinical and radiological
      examination with standard radiographs, arthrography and sonography included;
      sometimes as late as at surgery. In 15 joints with synovial type of septic
      arthritis pathological dislocation has been found. In 60 hips the inflammatory
      process involved proximal end of the femur. The sequelae strictly depended on
      localization of the pathology. On the basis of ossification disturbances,
      deformities and defects found within the head and neck on radiographs in 35 per
      cent of cases damaged epiphysis, physis and metaphysis were detected. In 23 per
      cent the neck was involved; in 42 per cent extensive damage to the head and neck
      was noted.

PMID- 7736808
TI  - [Usefulness of magnetic resonance imaging in diagnosis of selected diseases of
      the hip joint in children and adolescents].
AB  - The possibilities of MRI use for diagnostics of various conditions of the hip in
      children and adolescents are presented. The method proved to be highly valuable.

PMID- 7736809
TI  - [Histologic examination of slow epiphyseal distraction in the femur of rabbits].
AB  - Slow, symmetric epiphyseal distraction of the distal femur has been performed in
      30 immature rabbits aged 10 weeks (group 1) and 16 weeks (group 2). Histological
      examination has been carried out after 2, 4, 12 and 24 weeks of distraction in
      both groups. In all animals hyperplasia and hypertrophy of the distracted
      epiphysis and regular remodeling of the bony growth zone were found after 4 weeks
      of follow-up. No premature closure of the physis has been noted compared to the
      controls. Histological differences observed were attributed to various, age
      related biological potential and they resulted from physiological involution.

PMID- 7736810
TI  - [Multilevel osteotomy with Rush pin fixation in treatment of osteogenesis
      imperfecta].
AB  - Fourteen multilevel osteotomies with Rush pin fixation have been performed in 5
      children with osteogenesis imperfecta. The age of patients at the operation
      ranged from 6.5 to 15.5 years. Plaster of Paris immobilization never exceeded 8
      weeks. An axial correction, improved ambulating and equalization of the limbs
      have been achieved in all cases. Complications of the method included varus
      deformity of the proximal tibia (1 case), migration of the pin (1 case) and
      supracondylar fracture of the femur at the level of pin end (2 cases).

PMID- 7736811
TI  - [Zespol fixator for treatment of a pathologic fracture in Albright syndrome].
AB  - A case of 49 years old female with Albright syndrome who had a fracture of the
      femur is presented. After the use of Zespol fixator good clinical and
      radiological result has been achieved.

PMID- 7736812
TI  - [Maquet osteotomy for treatment of knee osteoarthritis].
AB  - Semicircular osteotomy within the proximal epiphysis of the tiba has been
      performed in 24 females with osteoarthritis of the knee. There were 16 cases of
      lateral compartment involvement with concomitant valgus deformity and 8 cases of
      medial compartment involvement with varus deformity. A follow-up clinical
      radiological assessment included 18 patients. Excellent results were found in
      27.7 per cent, good in 61 per cent, fair in 11.2 per cent of the cases. No poor
      results have been observed. High efficacy of this method along with its
      relatively low invasiveness and inconsiderable complication rate allows for its
      extensive use, even in the elderly patients.

PMID- 7736814
TI  - [Skew foot--etiology, clinical appearance, management].
AB  - Thirty feet in 18 children diagnosed as skew foot (Z-foot, serpentine foot) have
      been assessed. Following types of deformity have been distinguished: 1.
      idiopathic congenital (21 feet), 2. congenital, associated with other defects or
      systemic disease (8 feet), 3. acquired (iatrogenic) after manipulations for club
      foot treatment (1 foot) and 4. neurogenic, not represented in this study. In the
      first group minor forefoot adduction that remained after cast treatment was
      generally accepted by the parents; 7 feet required surgical release. Eight feet
      were corrected operatively in group 2. In most of the cases palliative procedures
      were performed due to late turning for surgery of children with systemic disease.
      In case of type 3 deformity termination of manipulations spontaneously led to the
      restoration of anatomy in the Chopart joint. According to the authors, surgery,
      preferably in the first year of life, offers full possibility to regain anatomy
      and shape of the foot.

PMID- 7736813
TI  - [Results of surgical treatment for fractures of the ankle].
AB  - The results of surgical treatment for fractures of the ankle have been presented.
      The patients were divided into two groups. The first one, treated between 1972
      and 1985, was examined twice after a mean follow-up of 5 and 9 years. An analysis
      of deteriorating cases was conducted-secondary arthritic changes prevailed. The
      second group consisted of patients treated between 1986 and 1989 with changed
      tactics of management. The mainstay of the surgery was stable reconstruction of
      the fibula and distal tibiofibular ligament. Those patients were examined once at
      a mean follow-up of 2.3 year. Seventy per cent of results were rated excellent or
      good.

PMID- 7736815
TI  - [An isolated post-traumatic intermediate cuneiform osteitis caused by pseudomonas
      aeruginosa].
AB  - A case of 49 years old cattle farm employee who developed intermediate cuneiform
      osteitis after stabbing the dorsum of the foot with a tool. The bone became
      entirely necrotic and has been removed surgically. An instillation combined with
      local and systemic antibiotic therapy resulted in cure. After 3.5 years of follow
      up neither static nor dynamic disabilities of the foot have been found.

PMID- 7736816
TI  - [Free vascularized skin flap from the scapular region for treatment of foot skin
      loss].
AB  - A case of 10 years old boy with foot skin loss due to the traffic accident is
      presented. Free vascularized skin flap from scapular area has been used. The
      healing was uneventful. Advantages and disadvantages of this type of flap have
      been discussed.

PMID- 7736817
TI  - [Early results of coracoclavicular ligament reconstruction with carbon fiber
      prosthesis in patients with acromioclavicular dislocation].
AB  - The results of surgical repair of coracoclavicular ligament with carbon fiber
      prosthesis in 34 patients with acromioclavicular dislocation have been presented.
      They were assessed on the basis of subjective opinion, clinical and radiological
      examination. Clinically 91 per cent results were rated excellent or good.
      Anatomical position of articular surfaces within acromioclavicular joint was
      found in 88 per cent of cases. The authors conclude, that carbon fiber
      ligamentous prosthesis proved its usefulness in surgical restoring of the
      stability of the acromioclavicular joint.

PMID- 7736818
TI  - [Lateral extra-canalicular lumbar disc herniation].
AB  - A case of 60 years old female with far-lateral disc herniation within lumbar
      spine is presented. The herniated disc has been excised from the lateral muscle
      splitting approach with the use of microscope.

PMID- 7736819
TI  - [Photoelastic study of fragment compression in fracture of the femoral neck
      stabilized with the Zespol hip fixator].
AB  - The paper presents analysis of the forces within fracture line of femoral neck
      stabilized with Zespol hip fixator. The investigation has been carried out on
      specifically designed model of the proximal femur; the forces were measured in
      photoelastic fashion with the use of epoxy resin cubes as dynamometers. The
      magnitude of forces within fracture line has been verified and related to the
      position of the platforms of the screws versus the plate before tightening the
      nuts.

PMID- 7736820
TI  - [Study of osteosynthesis strength in femoral neck fractures stabilized with a
      Zespol hip fixator].
AB  - Strength study have been carried out on two different osteotomies of the femoral
      neck stabilized with Zespol hip fixator, performed on fresh specimens taken out
      from cadaver. Stability of fixation has been assessed in transverse osteotomy of
      the neck (Pauwels I type of fracture) and in one parallel to the long axis of the
      femur (Pauwels III type). The results were compared to similar studies including
      different fixing methods (DHS, Thornton nail, von Bahr screw, Knowles pin) but
      identical types of osteotomy, published by other authors. Zespol fixation proved
      to be equal and frequently superior over other modalities in terms of mechanical
      stability.

PMID- 7736821
TI  - [Atypical position of the extremity after femoral neck fracture, case report].

PMID- 7736822
TI  - [Reconstruction of the femur with free vascularized bone graft].
AB  - A case of post-infection femoral bone loss treated with free vascularized fibular
      graft is presented. The healing process is discussed; an attention is directed
      towards thickening of the graft along with progressive weight bearing. The
      usefulness of Zespol fixation in those cases, allowing for early rehabilitation
      is underlined.

PMID- 7736823
TI  - [Vascularized bone graft treatment for pseudoarthrosis of the leg].
AB  - The use of pedicular and free vascularized grafts in treatment for
      pseudoarthrosis of the leg is discussed in this paper. These grafts are greatly
      useful in treatment of avascular pseudoarthrosis where severe vascular impairment
      is present. The transplantation of viable, vascularized bone graft to the site of
      pseudoarthrosis creates ultimate environment for bony union. A concomitant soft
      tissue transfer (muscles and skin) may compensate for potential skin defect at
      the recipient site. According to the authors the above discussed method deserves
      broader application in the treatment of pseudoarthroses, especially avascular
      ones.

PMID- 7736824
TI  - [Osteotomy of the medial cuneiform in the treatment of the adducted forefoot].
AB  - A series of 20 feet in 17 children (12 females, 5 males) treated surgically with
      medial cuneiform osteotomy and bony bloc insertion to correct forefoot adduction
      has been assessed. Primary diagnosis were: congenital clubfoot (17 feet),
      skewfoot (2 feet) and congenital fibular aplasia (1 foot). The average age at the
      operation was 4.5 years (range from 23 months to 8 years 2 months). Five children
      (7 feet) were operated before 4 years of age. Medial cuneiform osteotomy has been
      combined with complete subtalar release from Cincinnati approach, wedge resection
      of the cuboid and Dwyer procedure. The follow-up was 18 months on an average (6
      30 months). Correction of the deformity has been assessed clinically and
      radiologically (angles: tarsal-metatarsal I, tarsal-metatarsal V and first ray
      angle ray angle according to Barriolhet. In all cases accurate position of the
      forefoot has been achieved.

PMID- 7736825
TI  - [The study of afferentation in arthrogryposis].
AB  - The electroneurograms of the tibial and median nerve in children with
      arthrogryposis have been performed; excitability curves which characterizes the
      function of the nerves were recorded. Afferent conduction velocity in 30 examined
      nerves showed statistically significant slowing down. An amplitude of evoked
      potentials in the tibial and median nerves was decreased but the difference
      compared to the control group was not statistically significant. Histograms based
      on electroneurography indicate existence of two groups of results, that might
      reflect neurogenic and/or myogenic origin of arthrogryposis. Excitability curve
      has been moved upwards and to the right in one point only, characterizing the
      tibial nerve function; in 5 remaining points the differences with controls were
      not significant. All-over results indicate subclinical afferentation impairment
      within lower extremities in children with arthrogryposis.

PMID- 7736826
TI  - [Two cases of coexisting dysplasia fibrosa and mesenchymoma].
AB  - Two patients with dysplasia fibrosa who also had a tumor of mesenchymal origin
      are presented. One of them underwent one time resection of dysplasia fibrosa
      focus and the tumor, the other had the tumor resected 17 years after surgical
      resection of focus in the femur. The authors suggest an etiologic relationship
      between these two conditions based on mesenchymal changes--the occurrence never
      described previously. They also indicate efficacy of surgical treatment.

PMID- 7736827
TI  - [Carpal tunnel syndrome in hemodialyzed patients].
AB  - Eight patients hemodialyzed for 7-15 years, operated in Lublin Orthopedic
      Department because of carpal tunnel syndrome are presented. The pain, paresthesia
      and thenar muscles atrophy were present 4 to 12 months prior to the surgery.
      Phalen sign in those patients was absent due to restricted range of motion in
      wrist arthropathy. After transverse carpal ligament dissection a thickened,
      brownish peri-tendon encapsulating flexor tendons without usual gloss but with
      white spots has been seen. Microscopic examination revealed amorphic bodies
      surrounded by lymphoid-plasmatic infiltrate and amyloid deposits reacting with
      Congo red. At the follow-up examination (3 years after surgery on the average) no
      pain or paraesthesiae were found but thenar muscles atrophy and loss of
      opposition was permanent.

PMID- 7736828
TI  - [Pitfalls and failures in open reduction and stabilization of thoracolumbar
      fracture using Harrington rods].
AB  - A series of 26 patients with severe thoracolumbar burst fracture was treated with
      Harrington instrumentation. Pitfalls and failures in adequate stabilization are
      presented. In 2 cases vertebral arch supporting the hook was damaged. These
      patients required restabilization combined with anterior fusion. In another case
      sublaminar wire loop pulled by the hook compressed the dural sac. Long rods (over
      more then five segments) were usually applied for stabilization of several arches
      damage, most often cranially from the fracture site or developmental defects
      within L5 and S1. The best stabilization with short rods has been achieved within
      lumbar spine or in cases supplemented with anterior fusion with the use of bone
      graft.

PMID- 7736829
TI  - [Clinical analysis of 126 patients with spinal metastases].
AB  - A series of 126 patients with spinal metastases and spinal cord lesion treated
      between 1963 and 1992 at Neurosurgery Department in Poznan has been presented.
      Neurological condition of the patient, neuroradiological and histological
      examinations are presented; modalities of management and results are discussed.
      Treatment was depended on the patient's conditions. Surgery was undertaken if
      spinal metastasis was the first symptom of the disease. Sixty-one per cent of
      patients died within 6 months after being diagnosed. Survival was longer in
      patients treated surgically. Fifty-six percent of them became ambulatory and in
      majority free of radicular pain. The longest survival was in prosthetic
      metastases, the shortest in pulmonary ones.

PMID- 7736830
TI  - [Use of x-ray microanalysis and scanning electron microscopy to determine
      reactivity to the Weller endoprosthesis by body parts].
AB  - The long-term immunity against penetration of alloy components from the Weller
      stem into the bone cement and bone tissue has been investigated. No alloy
      elements (Co, Cr, Mo) contamination within cement or bone tissue has been
      observed in patients included in this study. The method employed proved valuable
      for chemical analysis within microareas of the hip after arthroplasty.

PMID- 7736831
TI  - [Surgical treatment of post-injection contracture of the hip in children].
AB  - Abduction contracture of the hip has been treated by two methods; the results of
      both have been compared. Modified Campbell's procedure has been performed in 5
      children (6 hips). In 8 patients (9 hips) gluteal fascia and fibrotic scarring
      within the gluteal muscles has been transversely dissected. The mean follow-up
      was 26 months in either group. Dissection of the fascia and the scars resulted in
      doubled range of adduction and better cosmetic result compared to Campbell's
      method.

PMID- 7736832
TI  - [Z-plasty in treatment of snapping hip].
AB  - The study deals with clinical assessment of results of surgical treatment of 13
      snapping hips. Bringnall and Stainsby procedure has been employed; the surgical
      technique has been described. The mean age at the operation was 19 years, mean
      follow-up was 21 months. In 11 cases (84.6%) the symptoms abated completely. The
      results justify conclusion, that Z-plasty with transposition of created flaps
      should be recommended as a mode of surgical treatment for snapping hip.

PMID- 7736833
TI  - [Foot deformity as a late consequence of tibial shaft fracture].
AB  - Clinical appearance of foot deformity after tibial shaft fracture resulting from
      the contracture of the deep posterior compartment muscles of the leg is presented
      in this paper. The contracture may be caused by mechanical damage to the muscles
      or vessels or by deep posterior compartment syndrome. Cavus deformity, shortening
      of the foot length, claw big toe and hammer lesser toes are frequently unnoticed
      at the follow-up examination after surgical treatment of the tibial fracture.
      These findings are based on analysis of 71 patients treated surgically for leg
      shafts fracture with AO method.

PMID- 7736835
TI  - [Companacci classification and result of treatment for aneurysmal bone cyst].
AB  - Results of treatment of 17 patients operated because of aneurysmal bone cyst have
      been assessed. Age at the onset of symptoms ranged from 4 to 39 years, 14 on an
      average. There were 6 aggressive and active cysts in this series according to the
      Campanacci classification. Treatment consisted of segmental resection of the bone
      in 5 patients, curettage of the lesion filing of the defect with autogenous bone
      in 11 cases. Recurrence of the cyst has been observed in 3 patients, only one of
      them had aggressive type of tumor.

PMID- 7736834
TI  - [Failure of functional treatment for humerus fracture in adults].
AB  - Results of functional hanging cast treatment for humeral fracture in 48 patients
      have been presented. Mean follow-up was 4 years. Good results were achieved in 35
      cases, fair in 10 and poor in 3 cases. The study confirmed, that the method leads
      to the fast fracture union and restoring function of the extremity. The failures
      were caused by insufficient patient's alertness. They also may occur in
      alcoholics and patients with generalized joint laxity if excessive distraction of
      fragments takes place.

PMID- 7736836
TI  - [Surgical treatment of brain metastases from sarcoma].
AB  - Brain metastases from sarcoma are rare, and data concerning the treatment and
      results of therapy are sparse. We retrospectively reviewed a series of 28
      patients with brain metastases from sarcoma, who were neuro-surgically treated in
      single institution over 20 years. There were 15 men and 13 women. In 21 patients
      the brain lesion was located in the supratentorial region, and in 7 patients
      infratentorially. The median age at brain metastasis diagnosis was 25 years
      (range 2.6-68 years). Median time from primary diagnosis to diagnosis of brain
      metastasis was 26.7 months. Lung metastases were present in 21 patients (76%) (8
      synchronous with the brain lesion). Pulmonary metastases were resected in 14
      patients (50%). The overall median survival time from diagnosis of primary
      sarcoma was 38.8 months, and from craniotomy was 6.6 months. The presence or
      absence of lung lesion did not change the median survival calculated from
      diagnosis of brain metastasis (7 mos and 4.5 mos, respectively, p < 0.48, log
      rank test). Two patients (7%) died within 30 days of operation. One-year survival
      was 36% and 2-year survival was 18%. Three patients (12%) survived over 5 years.
      Since brain metastases from sarcoma are refractory to alternative treatment,
      surgical excision is indicated when feasible. Brain metastases from sarcoma are
      uncommon and usually occur in association with or following lung metastasis. Long
      term survival is possible in a small percentage of patients.

PMID- 7736837
TI  - [A complicated case of multiple trauma in a 40-year old male patient].
AB  - The method, algorithm and result of treatment of 40 years old patient with
      multiple trauma has been presented. Despite ruptured diaphragm and pericardium,
      sub-diaphragm displacement of the heart and supra-diaphragm transposition of the
      stomach and bowels the final result was entirely positive.

PMID- 7736838
TI  - [Late ulnar nerve paresis in adults after neglected treatment for fracture of the
      capitulum with part of the trochlea in children].
AB  - Etio-pathomorphogenesis of compression syndromes of the ulnar nerve strained over
      the medial side of the valgus elbow is presented on the basis of follow-up of 11
      patients. Valgus deformity of the elbow resulted from neglecting of surgical
      reduction of the displaced capitulum and part of the trochlea in the childhood.
      Cartilage of the articular surface of the displaced fragment facing injury site
      of the humeral condyle impedes healing of the fracture and disturbs the growth of
      the lateral epiphysis. Thus valgus deformity is accompanied by pseudoarthroses
      and various deformities of the articular surface. Function of the distorted elbow
      joint was good, however, and the range of motion pretty wide. An irritation or
      late paresis of the ulnar nerve appeared only 17 or even 45 years after the
      fracture in childhood. Permanent ulnar paresis can be prevented by early nerve
      transposition, that is during first year of ulnar nerve irritation symptoms.

PMID- 7736839
TI  - [Pierre Brocq. 1884-1960].

PMID- 7736840
TI  - [Jean Perrotin (1916-1993)].

PMID- 7736841
TI  - [Inguinal hernia in adults. Subperitoneal prosthesis under celioscopic control
      (370 operated sides in 320 patients with 411 hernias)].
AB  - The authors present their technique of groin hernias repair by putting of a very
      tall (15 X 15 cm for unilateral hernias, or 30 X 15 cm for bilateral hernias).
      Polypropylene prosthesis in subperitoneal space by laparoscopic access. From may
      1991 to june 1993, 320 patients were operated on 370 sides (50 bilateral hernias)
      with a total of 411 hernias. The first results are analysed: there was in
      particular no conversion and infection. Recurrences were studied only on the
      patients operated since at least one year: There were 1 recurrence (0.6%) on 163
      sides operated in 141 patients with a mean average follow up of 17 months. There
      were 2 occlusions (on 370 sides operated), by incarcerated small bowel in the
      preperitoneal space after partial failed of the peritoneal suture. The first
      patient was reoperated on at the fifteenth postoperative day (chronic occlusion)
      by laparotomy. The second patient was reoperated on at the fifth postoperative
      day by laparoscopy which permit to reduce the small bowel in the abdominal cavity
      and closing the peritoneum with a new suture. It should be observed that 74
      patients (23%) were operated on epidural anesthesia.

PMID- 7736842
TI  - [The use of cadavers for the demonstration of celioscopic surgery].

PMID- 7736843
TI  - [Subcutaneous mastectomies. Apropos of 272 cases].
AB  - Subcutaneous mammectomy was performed in 272 patients with reconstruction in 256.
      This type of surgery lies midway between conservative surgery and mammectomy. The
      conditions of exeresis and prosthetic reconstruction, follow-up (recurrences and
      metastasis) were analyzed according to each histological type and were comparable
      with the usually reported results for breast cancer. Likewise, the cosmetic
      results were staged to analyze the different criteria allowing a symmetrically
      satisfactory reconstruction. Out come was globally satisfactory (70% good
      results). The only drawback for subcutaneous mammectomy would be the need to use
      a prosthesis which requires expertise in both breast surgery and plastic surgery.

PMID- 7736844
TI  - [Esophagectomy without thoracotomy. Comparison between a retrospective study and
      a prospective randomized trial].
AB  - From 1983 to 1989, 96 oesophagectomies (30% of all oesophagectomies performed
      during this period) were performed without thoracotomy and then analyzed
      retrospectively. Most were performed due to contraindications including age
      (17%), respiratory disease (47%), heart disease (37%) or for superficial
      oesophageal lesions (35% were stage T1). Operative mortality was 3.1%.
      Fistulization of the anastomosis occurred in 7.5% of the cases. Actuarial
      survival rate at 5 years was 29% and was independent of age but dependent on
      localization, the size of the tumour, presence of parietal invasion and TNM
      classification. However, patient selection introduced bias and a prospective
      randomized study comparing oesophagectomy without thoracotomy and oesophagectomy
      via right thoracotomy and midline incision demonstrated that mortality and
      complications were similar with the two techniques. Long term survival was not
      dependent on access route, but on the stage of the disease.

PMID- 7736845
TI  - [Constipation in children. Value of anorectal sphincteromyectomy].
AB  - Anorectal sphincteromyectomy is a suitable answer to the problem of the chronic
      constipation in childhood. It took a long time to be recognized beside others
      methods as biofeedack. This surgical procedure has been described for the first
      time by B. Duhamel in 1965; we still remained faithful and proud of this idea. We
      wanted to understand and to explain the basis of the conception of anorectal
      achalasia. Several works about the fetal development of the anorectal sphincter
      tried to explain it. A good exposition makes the technique less difficult and the
      dissection of the internal sphincter easier. We have analysed our 22 recent
      children. In 21 cases, we noticed a good result. The histological study of the
      fragment of the myomectomy showed a normal cytology of the smooth muscular
      tissue, a normal intrinsic innervation and arterial vascularisation. The surgical
      procedure is efficient because it relieves the functional disorder of the
      internal anal sphincter. It is a mechanical action; the external sphincter finds
      again its normal function, or is allowed to be reeducated.

PMID- 7736846
TI  - [How to reduce morbidity in celioscopic biliary surgery. Apropos of a series of
      446 consecutive operations].
AB  - We reported a series of 446 consecutive cholecystectomies performed
      laparoscopically between June 1990 and January 1993. There were 354 females and
      92 men, mean age 53 +/- 17 years. Laparoscopic cholangiography was attempted in
      410 cases (92%) and led to the discover of a stone in the main bile duct in 18
      cases (4%) and an abnormal insertion of the bladder duct in 30% (6.7%).
      Conversion to laparotomy was required in 84 patients (18.8%) due to difficult
      dissection (52), peroperative incidents or accidents (15) and abnormal hepatogram
      (17). No accident inherent to the operation was encountered in this series. One
      death occurred after laparotomic conversion for acute angiocholitis. The rate of
      post-operative complications was 5.6% and reoperations were required in 7
      patients (1.5%).

PMID- 7736847
TI  - [Management of splenic contusion. Apropos of the communication of P. Verhaeghe
      and al. Meeting of 1993 December 15].

PMID- 7736848
TI  - Ethnobotany and the Search for New Drugs. Symposium proceedings. Fortaleza,
      Brazil, 30 November-2 December 1993.

PMID- 7736849
TI  - Amazonian ethnobotany and the search for new drugs.
AB  - Tropical rain forests offer enormous prospects for the discovery of new drugs for
      use in Western medicine. The Amazon supports 80,000 species of higher plants and
      a diverse Indian population. Focusing attention on those plants used as medicines
      by indigenous peoples is the most efficient way of identifying the plants that
      contain bioactive compounds. There is an urgent need for more ethnobotanists and
      ethnopharmacologists to be trained to document as much information as possible
      before it and the plants are lost through destruction of the rain forest and
      acculturation of the indigenous peoples. Ethnobotanical studies have identified
      plants documented by early travellers; these include Paullinia yoco and Ilex
      guayusa which are used as stimulants and have been shown to be rich in caffeine.
      Studies of the hallucinogen prepared from Banisterioposis caapi have shown that
      the native people know which plants to add to the mixture to lengthen and
      intensify the intoxication produced by the beta-carboline alkaloids in the plant.
      Three major snuffs are used in the Amazonia; the plants from which they are
      derived have been identified. One of the snuffs also has antifungal and curare
      like activities; chemical analysis on the active principles has not been done.
      Several plants are considered as prime candidates for scientific study as sources
      of useful chemicals for medicine or industry. These include some used to prepare
      teas or other infusions for treatment of various symptoms of senile dementia.

PMID- 7736850
TI  - African medicinal plants in the search for new drugs based on ethnobotanical
      leads.
AB  - In the African world view the natural environment is a living entity whose
      components are intrinsically bound to mankind. Dietary plants, spices and common
      herbs dominate the materia medica, in contrast with modern orthodox medicine
      which uses many regulated poisons. Drug development based on ethnobotanical leads
      has followed two paths: the classical approach of identification of single plant
      species with biologically active compounds and the characterization and
      standardization of traditional recipes for reformulation as medicines. The first
      approach has led to the recognition of many African plants as medicines and the
      isolation of several biologically active molecules; examples range from the well
      physostigmine (from Physostigma venonosum) used for the treatment of glaucoma to
      the recently identified antiviral agents from Ancistrocladus abbreviatus. The
      second approach which aims at optimization of mixed remedies as formulated dosage
      forms is perhaps more relevant to the needs of the poor rural populations but has
      remained largely ignored. Drug development programmes based on ethnobotanical
      leads must provide for just and fair compensation for individual informants and
      local communities.

PMID- 7736851
TI  - Two decades of Mexican ethnobotany and research in plant drugs.
AB  - A renewed interest in the systematic study of indigenous medicines and associated
      medicinal plants arose in the 1970s. In Mexico the government established a
      national pharmaceutical industry to make use of the valuable colonial heritage of
      traditional practices combined with European medical concepts and resources. In
      1975 the Mexican Institute for the Study of Medical Plants was created to
      integrate botanical, chemical and pharmacological studies on the Mexican flora.
      It compiled a database on ethnobotanical information relating to Mexican
      medicinal plants from the medical literature of the 16th to 19th centuries. A
      second database contained information on medicinal plants in current use. A
      medicinal herbarium was established. Taxonomical studies led to classification of
      the 11,000 voucher specimens in the herbarium and cross-referencing of the
      information with other databanks. A core group of 1000 plants used in traditional
      medicine throughout Mexico for almost 400 years was identified. Most of these are
      used to treat common diseases or basic health problems, usually given orally as
      decoctions or infusions. 95% of the plants used traditionally are from wild
      species. Information was collected from almost 3000 small Indian communities over
      four years on three aspects of traditional medicine--the healer, the disease
      categories recognized and the therapeutic resources in use. Plants with reported
      medicinal activity were selected for laboratory screening according to the
      frequency and commonality of their use, geographical distribution and seasonal
      availability. Screening involves a collaboration between chemists and
      pharmacologists: plant extracts are sequentially assayed and fractionated until
      the pure compound is isolated. Several active compounds are usually obtained from
      the same extract, frequently from the aqueous fractions. Ethnomedical information
      influences which plants are selected for screening and the type of assay used.

PMID- 7736852
TI  - Ethnobotany and research on medicinal plants in India.
AB  - Vast ethnobotanical knowledge exists in India from ancient time. Since the 1950s
      the study of ethnobotany has intensified; 10 books and 300 papers have been
      published. Our work over four decades, both in the field and literary studies,
      has resulted in a dictionary of Indian folk-medicine and ethnobotany that
      includes 2532 plants. India has about 45,000 plant species; medicinal properties
      have been assigned to several thousand. About 2000 figure frequently in the
      literature; indigenous systems commonly employ 500. Despite early (4500-1500 BC)
      origins and a long history of usage, in the last two centuries Ayurveda has
      received little official support and hence less attention from good medical
      practitioners and researchers. Much work is now being done on the botany,
      pharmacognosy, chemistry, pharmacology and biotechnology of herbal drugs. The
      value of ethnomedicine has been realized; work is being done on psychoactive
      plants, household remedies and plants sold by street drug vendors. Statistical
      methods are being used to assess the credibility of claims. Some recent work in
      drug development relates to species of Commiphora (used as a hypolipidaemic
      agent), Picrorhiza (which is hepatoprotective), Bacopa (used as a brain tonic),
      Curcuma (antiinflammatory) and Asclepias (cardiotonic). A scrutiny of folk claims
      found 203 plants for evaluation. Less well known ethnomedicines have been
      identified that are used to treat intestinal, joint, liver and skin diseases.

PMID- 7736853
TI  - Ethnopharmacological investigation of Chinese medicinal plants.
AB  - Chinese medicinal plants, which have been used by the Chinese people for
      centuries, are still being widely used today within the framework of healthcare
      services. A recent nationwide survey has shown there are 7295 species of plants
      used medicinally in China. An ethnopharmacological investigation included
      families containing over 100 medicinal plant species in Chinese medical flora, as
      well as genera containing over 15 medicinal species with a high proportion of
      therapeutic members. Medicinal plants are an important source for new drug
      development in China. Up to now about 200 new drugs have been developed directly
      or indirectly from Chinese medicinal plants. Nearly one half of the new drugs are
      from a single Chinese medicinal plant, or its active principle(s) and synthetic
      derivatives, or active fraction(s) or even the total extract. More than half are
      from composite prescriptions.

PMID- 7736854
TI  - Ethnobotany and drug discovery: the experience of the US National Cancer
      Institute.
AB  - Between 1960 and 1981 the National Cancer Institute (NCI) screened 114,000
      extracts of 35,000 plants, mainly collected in temperate regions. Of the three
      clinically active anticancer drugs so far discovered in that programme, none was
      isolated from a plant collected on an ethnobotanical basis, though various Taxus
      species, which are the source of taxol, are reported to have been used
      medicinally. Since 1986, the NCI has focused its collections in tropical and
      subtropical regions worldwide; collections cover a broad taxonomic range, though
      priority is given to medicinal plants when relevant information is available. As
      of August 1993, 21,881 extracts derived from over 10,500 samples had been tested
      in a screen for activity against the human immunodeficiency virus (HIV); 2320 of
      these extracts were of medicinal plant origin. Approximately 18% of both the
      total number of extracts and the medicinal plant-derived extracts showed
      significant anti-HIV activity; in each instance about 90% of the active extracts
      were aqueous. The activity of the aqueous extracts has been attributed mainly to
      the presence of polysaccharides or tannins. Four plant-derived compounds are in
      preclinical development at the NCI; only one of the four sources plants, obtained
      from a noncontract source, was collected on an ethnobotanical basis. At this
      stage the results indicate that the current NCI collection policy offers the best
      chances for the discovery and development of agents for the treatment of AIDS
      (acquired immune deficiency syndrome) and cancer.

PMID- 7736855
TI  - From shaman to human clinical trials: the role of industry in ethnobotany,
      conservation and community reciprocity.
AB  - Shaman Pharmaceuticals is a development-stage company engaged in developing
      traditional pharmaceuticals identified through a discovery process focused on
      isolating active compounds from tropical plants with a history of medicinal use.
      This process has resulted in two products in clinical trials: Provir, an oral
      product for the treatment of respiratory viral infections, and Virend, a topical
      antiviral product for the treatment of herpes. Shaman's drug-discovery process
      targets specific plants that have been used for medicinal purposes by native
      peoples. By integrating the sciences of ethnobotany, medicine and plant natural
      product chemistry, Shaman has been able to achieve time and cost savings for the
      identification of active compounds and preclinical development of its initial
      products. Numerous drugs have entered the international pharmacopoeia via the
      study of ethnobotany and traditional medicine. Two important elements of this
      approach to drug discovery are the percentage of plants that show activity
      against specific viral pathogens and the correlation between the folk therapeutic
      classification of plants used and the percentage of those plants that have shown
      activity in our antiviral screens. Conservation and direct reciprocity to
      indigenous communities are important features of Shaman Pharmaceuticals' drug
      discovery process.

PMID- 7736856
TI  - Ethnobotany and intellectual property rights.
AB  - Contemporary intellectual property law permits only the patenting of an
      identified active principle from a plant, not the plant or folk information
      relating to medicinal properties of a plant. The most significant rights of
      indigenous peoples are those deriving from physical control of the plants and the
      knowledge pertaining to their use. This control can provide the basis for trade
      secret protection. Such agreements are enforceable in developed nations and
      should become so in developing nations. There have been recent efforts to
      strengthen indigenous peoples' rights over genetic resources and relevant folk
      knowledge but the most far-reaching of these are not yet a part of international
      law. Pharmaceutical patents combined with trade secrecy can allow firms to
      develop and market products and ensure that the nation and/or people from which
      the material or information was derived are properly rewarded. This does not
      provide protection from competition or with respect to derived knowledge nor does
      it act retrospectively. At present, rights under the United Nations Convention on
      Biodiversity are prospective only. These rights belong to the nation and there is
      little legal pressure for recompense to be shared with indigenous peoples. A
      uniform agreement that deals in a balanced way with the relative rights of
      indigenous peoples and of their governments should be developed by non
      governmental organizations.

PMID- 7736857
TI  - Conservation and ethnobotanical exploration.
AB  - In recent years conservationists have realized that the maintenance of protected
      areas is closely linked to rural development. As part of their efforts to improve
      local people's standards of living, they have sought the advice of researchers
      who work in communities, especially those that border on nature reserves.
      Ethnobotanists, who are turning their attention to the cultural and ecological
      crises confronting the regions in which they work, are natural allies in this
      venture. The joint efforts of conservationists and ethnobotanists are being
      supported by non-profit organizations, intergovernmental agencies and research
      institutes. The search for new drugs and other natural products from plants is an
      important element in this collaboration, but it cannot be divorced from the
      broader objective of promoting the survival of biological and cultural diversity.
      Conservationists will support biodiversity prospecting and related efforts only
      if there is a clear benefit for local communities and protected areas. An example
      of the concrete actions being taken by conservation agencies is the People and
      Plants Initiative, a joint effort of the World Wide Fund for Nature, the United
      Nations Educational, Scientific and Cultural Organization and the Royal Botanic
      Gardens, Kew. The main objective is to support the work of ethnobotanists in
      developing countries in studies of sustainable plant use and application of their
      work to conservation and community development. The initiative provides training
      workshops and relevant literature; coordinators work in collaboration with local
      people to create inventories of useful plants and appraise the impact of
      harvesting specific plant resources in and around protected areas. Phytochemical
      screening of medicinal plants and preparation of extracts are carried out as part
      of some projects.

PMID- 7736858
TI  - Anthropological issues in medical ethnobotany.
AB  - While ethnobotany has emerged as an important discipline in the search for new
      drugs, this economic impetus should in no way distract from a more
      ethnobiological and equally critical goal--the codification and promotion of
      indigenous medical systems as a major factor in the conservation of biocultural
      diversity. Codification of indigenous medical systems requires a holistic view
      which entails (1) in-depth understanding of the recognized health conditions in
      the native system and how they might be described in terms of Western
      biomedicine; (2) comprehensive inventories of medicinal species employed in the
      native system, descriptions of their modes of preparation and administration and
      giving priority to those species most likely to merit pharmacological testing;
      and (3) identification of the pharmacological properties of these species with
      the goal of discovering how they might be effective in the treatment of the
      health conditions for which they are employed. Promotion of indigenous medical
      systems requires the development of local training programmes aimed at the active
      conservation and enhancement of traditional herbal medicinal therapies that have
      been shown to be pharmacologically effective in the treatment of symptoms of
      recognized health conditions. The establishment of such programmes is critical at
      a time when traditional medical systems are often disparaged as worthless by the
      national societies in which indigenous peoples live, as well as by younger
      members of the native populations themselves.

PMID- 7736859
TI  - The ethnobotanical approach to drug discovery: strengths and limitations.
AB  - For pharmaceuticals ranging from digitalis to vincristine the ethnobotanical
      approach to drug discovery has proven successful. The advent of high-throughput,
      mechanism-based in vitro bioassays coupled with candidate plants derived from
      pain-staking ethnopharmacological research has resulted in the discovery of new
      pharmaceuticals such as prostratin, a drug candidate for treatment of human
      immunodeficiency virus, as well as a variety of novel antiinflammatory compounds.
      Not all Western diseases are equally likely to be recognized by indigenous
      peoples. Gastrointestinal maladies, inflammation, skin infections and certain
      viral diseases are likely to be of high saliency to indigenous healers, whereas
      diseases such as cancer and cardiovascular illness are unlikely to be easily
      diagnosed by indigenous peoples. Yet indigenous remedies may indicate
      pharmacological activity for maladies such as schizophrenia, for which the
      biochemical mechanisms have yet to be discovered. Ethnopharmacological
      information can be used to provide three levels of resolution in the search for
      new drugs: (1) as a general indicator of non-specific bioactivity suitable for a
      panel of broad screens; (2) as an indicator of specific bioactivity suitable for
      particular high-resolution bioassays; (3) as an indicator of pharmacological
      activity for which mechanism-based bioassays have yet to be developed.

PMID- 7736860
TI  - Ethnobotany, drug development and biodiversity conservation--exploring the
      linkages.
AB  - Numerous ethnobotanical studies aimed at identifying new pharmaceutical products
      have been initiated in recent times. Ethnobotany has once again become a
      recognized tool in the search for new pharmaceuticals. Initiatives by
      governmental agencies and the private sector have helped spark this renewal. Many
      of these projects are interdisciplinary efforts involving scientists from the
      fields of anthropology, botany, medicine, pharmacology and chemistry. The Belize
      Ethnobotany Project links pharmaceutical prospecting with the conservation of
      traditional medical systems and biological resources. It illustrates the concept
      of the 'ethno-biomedical reserve' and provides an opportunity for pharmaceutical
      and herbal industries to contribute to the conservation effort. Terra Nova
      Rainforest Reserve is an ethno-biomedical reserve in Belize that was given legal
      status in June of 1993. Too often the exploitation of wild harvested resources
      has led to their severe degradation. There is a need for increased efforts to
      develop technologies to sustain their extraction.

PMID- 7736861
TI  - Ethnopharmacology and drug development.
AB  - The value of ethanomedical information in drug development is based on several
      factors: accuracy in recording or observing the medical use of the ethnomedical
      preparation, whether or not the ethnomedical use can be corroborated under
      scientific conditions in the laboratory, the formal or informal experience of the
      practitioner who provides the information, the role of the placebo effect and
      perhaps many others. Published ethnomedical information has many strengths and
      weaknesses relative to the ability to establish a corresponding biological effect
      in the laboratory. Many of the publications contain insufficient detail for the
      laboratory scientist. The ability to correlate ethnomedical reports with
      corresponding scientific studies could lead to improved selection of plants for
      further study in the areas of arthritis, cancer, diabetes, epilepsy,
      hypertension, malaria, pain and fungal and viral infections. These analyses have
      been accomplished by computer analysis utilizing the NAPRALERT database. This
      combination of analysing ethnomedical information and published scientific
      studies on plant extracts (ethnopharmacology) may reduce the number of plants
      that need to be screened for drug discovery attempts, resulting in a
      corresponding greater success rate than by random selection and mass
      bioscreening.

PMID- 7736862
TI  - Basic, quantitative and experimental research phases of future ethnobotany with
      reference to the medicinal plants of South America.
AB  - Ethnobotany of the future will encompass what we perceive as three interrelated
      research phases. Basic ethnobotany includes the compilation and organization of
      information about biota obtained from indigenous and other peoples, such as
      obtaining data about useful plants and animals, understanding how peoples manage
      their environments and learning about their lexicons and classifications. This is
      what we try to do in the best possible way, directly in the field from original
      sources. These results can then be organized in many ways once species
      determinations are completed. They may also be organized using other types of
      information, the most obvious being chemical, medical and linguistic.
      Quantitative ethnobotany develops methods to allow quantitative description and
      to evaluate and analyse primary data sets. Original field research must be
      sufficiently structured and consistent, for example in relation to forest habitat
      and composition or to oral exchanges between informant and listener, so that
      statistical techniques may be used to test proposed hypotheses rigorously. This
      aspect of ethnobotany is in its infancy, yet it can be broadly utilized to
      comprehend more meaningfully and usefully ethnobotanically valued plants,
      particularly in the exceedingly diversified environments of tropical regions
      where because of community isolation practitioners are still most knowledgeable.
      Experimental ethnobotany involves the use of biota in search of products for
      industrial, medical and other purposes. Plant ethnomedicinal findings may set the
      stage for targeting materials which can be meaningfully analysed for chemical
      activity using appropriate biodirected assays. This approach in search of new
      pharmaceuticals is woefully underutilized today to the detriment of human health
      and a number of new strategies should be considered for future advancements in
      drug discovery. These aspects of ethnobotany will be evaluated largely in
      relation to current and future research in South America.

PMID- 7736863
TI  - Ethnopharmacological search for antiviral compounds: treatment of
      gastrointestinal disorders by Kayapo medical specialists.
AB  - The Mebengokre (Kayapo) of Brazil have a highly developed medical and
      pharmacological tradition based on diverse specialization in knowledge and
      practice. Shamans (wayangas) are prepared to treat all kinds of diseases
      including those related to spirits; curers (makute pidja mari) can deal only with
      diseases not related to spirits. Both utilize plant- and animal-based remedies,
      among other practices. Elaborate disease categories (kane) include those known as
      hak-kane (bird disease) and tep-kane (fish disease). The complexity of the two
      categories defies easy description but both use gastrointestinal disorders as
      basic indicative symptoms. Given that an important percentage of gastrointestinal
      disorders are caused by viruses and that new antiviral drugs are sorely needed,
      plants used by the Kayapo for hak and tep diseases are presented and discussed as
      potential leads in the search for antiviral compounds.

PMID- 7736864
TI  - Natural product chemistry in north-eastern Brazil.
AB  - The north-eastern region of Brazil comprises about one third of the country's
      territory. It is a semi-arid region with a flora rich in aromatic, toxic and
      medicinal plants. Screening of aromatic plants led to the investigation of about
      2000 samples of essential oil from plants from the region and from abroad.
      Studies done by the Universidade Federal do Ceara and other research groups in
      the region discovered several new substances with distinct pharmacological
      activities. Recent examples are: schultezin, hydroxy-bisabolol, trans-annonene, (
      )-hardwickic acid, trans-cascarillone, nor-cucurbitacins, oleanolic saponin and
      chalcone dimer. A social programme called the Living Pharmacy was created to
      teach poor people how to cultivate and use medicinal plants correctly. A project
      to develop interaction between the university and industry also arose from these
      studies.

PMID- 7736865
TI  - Luminescence quenching by long range electron transfer: a probe of protein
      clustering and conformation at the cell surface.
AB  - Quenching of luminescence from fluorescent and phosphorescent probes by nitroxide
      spin labels with a long range electron transfer (LRET) mechanism (44,45) has been
      tested as a tool to monitor association/clustering and conformational changes of
      cell surface proteins. The membrane proteins were labeled with monoclonal
      antibodies or Fab fragments conjugated with luminescent probes or water-soluble
      nitroxide spin labels. The method was tested as a probe of 3 different aspects of
      protein-protein association involving class I MHC molecules: (1) interaction
      between the heavy and light chains of the MHC molecules, (2) clustering, self
      association of MHC molecules, (3) proximity of MHC molecules to transferrin
      receptors of fibroblasts or surface immunoglobulin molecules of B lymphoblasts.
      The extent of quenching upon increasing the fractional density of the quencher
      was sensitive for protein association in accordance with earlier
      immunoprecipitation and flow cytometric Forster-type energy transfer (FCET) data
      obtained on the same cells. These data suggest that the LRET quenching can be
      used as intra- or intermolecular ruler in a 0.5-2.5 nm distance range. This
      approach is simpler (measurements only on donor side) and faster than many other
      experimental techniques in screening physical association or conformational
      changes of membrane proteins by means of spectrofluorimetry, flow cytometry, or
      microscope based imaging.

PMID- 7736866
TI  - High-speed photodamage cell selection using a frequency-doubled argon ion laser.
AB  - A flow cytometer was developed for the high-speed "sorting" of desired cells by
      selectively irradiating (zapping) the undesired cells from a population. After
      previous efforts to photoinactivate cells with photosensitizers had failed, it
      was decided to exploit the photosensitivity of the cell's DNA at 257 nm. It was
      shown that a 257 nm laser output power of 20-100 mW was sufficient to induce a
      4.5 log cell kill after the cells were processed through a focused 257 nm laser
      beam. Experiments proved that the photodamage flow cytometer (ZAPPER) could
      selectively photoinactivate cells at rates over 22,000 events/s, and selection
      purities ranged from 81% to 100%. The yields of the desired cells depended on the
      selection mode. In the Enrichment mode, the zap laser was not aimed at the jet,
      and only undesired cells were exposed to a brief ultraviolet (UV) pulse after
      modulation of the UV laser beam. The yields of desired cells ranged from 95% to
      105%. In the Purge mode, the zap laser beam was aimed onto the jet, and only
      desired cells were allowed to pass after deflection of the UV laser beam; the
      yields of desired cells ranged from 12% to 52%. The cause of the reduced yields
      in the PURGE mode was traced to the fact that the Electro-Optic Modulator was
      used to modulate the zap laser proved too slow for the intended application. The
      lifetime of the frequency-doubling crystal used for the generation of the 257 nm
      beam was found to be limited to several days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736867
TI  - Modulation of membrane fluidity and lipidic metabolism in transformed rat
      fibroblasts induced by the sesquiterpenic hormone farnesylacetone.
AB  - Farnesylacetone is a natural terpene extracted from androgenic glands of the
      crustacean Carcinus maenas and is capable of inhibiting proliferation, notably in
      transformed mammalian cells. Flow cytometry with three lipophilic probes,
      diphenylhexatriene, trimethylammonium-diphenylhexatriene, and Nile red, has
      revealed modifications of the lipidic metabolism in transformed FR3T3-mTT4 rat
      fibroblasts treated by farnesylacetone, including changes in membrane fluidity.
      Farnesylacetone strongly increased the number of neutral lipidic droplets in the
      cytoplasm. Moreover, after prolonged terpene treatment, the membrane fraction of
      cells contained a substantial level of triglycerides. Farnesylacetone provoked an
      immediate but transitory increase in membrane fluidity of the cell membrane. The
      change in measured lipid fluidity appears to be due to these triglycerides rather
      than to the phospholipids.

PMID- 7736868
TI  - Kinetic analysis of glutathione in anchored cells with monochlorobimane.
AB  - A method for the measurement of intracellular glutathione content and glutathione
      S-transferase activity with monochlorobimane in adherent cells is described. The
      method involves the kinetic analysis of monochlorobimane conjugation to
      glutathione over a relatively short period of time. This permits extrapolation
      over time for determination of equilibrium fluorescence intensity (relative
      glutathione level) from scan intensity data that follows first-order kinetics,
      minimizing problems commonly associated with the use of monochlorobimane. By
      using measured fluorescence intensity values from glutathione standards, a
      suspension calibration curve was generated and, subsequently, was used to
      determine the photomultiplier tube saturation rate. A theoretical intracellular
      calibration curve was then generated to quantify glutathione content in cells.
      This method was also applied to study the changes in glutathione in a variety of
      rodent and human cell lines and in selected cocultures of cells exhibiting
      similar or different glutathione levels. Comparison of the glutathione levels
      obtained with monochlorobimane and a standard colorimetric method (GSH-400)
      indicated good correlation between the two methods. These studies support the use
      of laser cytometry for measuring intracellular glutathione with monochlorobimane
      as well as changes in glutathione occurring in cells that establish physical
      contacts with other cells. Laser cytometric analysis of glutathione in anchored
      cells also provides opportunities to monitor individual cellular responses to a
      variety of experimental manipulations, such as responses to various toxic insults
      or the protective effects of gap junction-mediated intercellular communication.

PMID- 7736869
TI  - Measurement of intracellular pH in mammalian sperm cells under physiological
      conditions.
AB  - The goal of this study was to develop a technique for the measurement of
      intracellular pH (pHi) in living mammalian (bovine) sperm cells under
      physiological conditions. Like many other biochemical measurements, pHi
      measurements have typically been made under non-physiological conditions on cells
      whose immediate functional status is not readily assessed and may even be non
      viable. Additionally, many pHi measurement techniques may themselves alter the
      pHi of the cells being measured. Such measurements could yield misinformation.
      The sperm cell is unique in that its functional status can be easily and
      continuously monitored by means of its motility, which is directly affected by
      pHi. In this respect, the sperm cell provides an ideal model system for
      evaluating pHi measurement techniques. In this article we summarize the
      validation of a ratiometric absorbance technique for the measurement of pHi of
      mammalian (bovine) sperm cells under physiological conditions which does not
      affect their functional status. The pHi of ejaculated bovine sperm cells was
      calculated to be 6.9 +/- 0.05 (11 replicates). This approach may also be suitable
      for pHi measurements in other cell types.

PMID- 7736870
TI  - DNA and RNA content analysis by flow cytometry in the pathobiologic assessment of
      bone tumors.
AB  - Studies of simultaneous DNA and RNA contents by flow cytometry in hematologic and
      some solid neoplasms have been shown to provide information that may be useful in
      the pathobiological evaluation of these neoplasms. We contend that similar
      analysis may be equally valuable in assessing bone tumors. Our data revealed
      significant statistical differences in DNA ploidy and proliferative fraction
      between benign and malignant bone neoplasms. Benign tumors manifested
      predominantly DNA diploidy and low proliferative activity, whereas the majority
      of malignant tumors were DNA aneuploid and showed high proliferation rate. No
      significant difference in the RNA content between different histopathologic
      categories was found. We observed, however, a distinct and consistently high RNA
      content pattern in giant cell tumors, aneurysmal bone cysts, and chondroblastomas
      that may be useful in their differential diagnosis. Analysis of different
      prognostic factors in malignant tumors indicated that histologic grade and DNA
      content are a significant prognostic factors. Further analysis of malignant
      tumors showed that a correlation between the proliferative activity and the
      clinical outcome in the low grade category and between RNA content and patients'
      survival in osteosarcomas. Our study also showed that preoperative treatment
      significantly impacted on the extent of the proliferative fraction in malignant
      tumors. We conclude that DNA/RNA analysis of bone tumor may assist in: (1) the
      differential diagnosis of certain bone tumors, (2) evaluation of treatment
      response, and (3) the biological assessment of osteosarcomas.

PMID- 7736871
TI  - Usefulness of the scraping method for DNA flow cytometry in breast tumors.
AB  - Flow cytometric DNA analysis is an important prognostic tool in breast cancer. We
      evaluated the possibility of performing DNA analysis on cell suspensions obtained
      by scraping the cut surface of breast tumors; 31 breast tumor nodules, including
      six benign and 25 malignant lesions, were studied. From each case, cell
      suspensions acquired by mechanical mincing of a fresh frozen tissue fragment and
      by two different scrapings (central and peripheral) from the cut surface of the
      tumor were analyzed via flow cytometry. In all cases, comparison of the DNA
      histograms for three samples showed no significant differences in the appearance
      of debris or in the value of coefficient of variation of the G0-G1 peak. All
      benign nodules showed a normal DNA stemline in all specimens. In 23 of 25 cases
      of breast carcinoma, the ploidy of the three preparations was similar, with a
      concordance in 12/14 (85, 71%) cases in DNA nondiploid tumors. Linear regression
      analysis showed a good correlation in DNA index between either scraping sample
      and the tissue fragment (r = .955 and r = .905). The results indicate that the
      scraping technique provides excellent cell suspensions and DNA histograms
      comparable to those obtained from mechanical mincing of tissue fragments. The
      technique minimizes preparation time and avoids consuming much tissue and, thus,
      is the method of choice when very small cancers have to be analyzed.

PMID- 7736872
TI  - Limited loss of nine tumor-associated surface antigenic determinants after
      tryptic cell dissociation.
AB  - Disodium ethylenediaminetetraacetic acid (EDTA) or trypsin/EDTA are frequently
      used for the dispersion of monolayer cells into single cell suspensions allowing
      flow cytometric analysis of surface antigenic determinants. A disadvantage of
      EDTA is the slow action of this agent, whereas trypsin might affect the antigenic
      determinants under focus. We studied the possible deleterious effect of trypsin
      on three different ovarian carcinoma cell lines, COV413b, COV362.c14, and
      NIH:OVCAR-3, on cell surface antigenic determinants by flow cytometry. Either
      EDTA or trypsin/EDTA was used for detachment and dissociation of monolayer
      ovarian cancer cell lines, followed by indirect immunofluorescence with a panel
      of monoclonal antibodies directed against nine different surface antigenic
      determinants, including six markers directed against widely distributed antigens.
      Compared to EDTA, trypsin/EDTA resulted in higher total cell yields and rapid
      detachment and dissociation into single cell suspensions with significantly lower
      amounts of dead cells detected by both trypan blue and propidium iodide (PI).
      Large differences in antigen expression were observed for the different cell
      lines. However, all antigenic determinants tested could still be detected after
      tryptic proteolysis. Three antigenic determinants were significantly decreased
      after trypsin/EDTA compared to EDTA detachment. CA 125 was decreased on
      COV362.c14 and NIH: OVCAR-3 cells, respectively. BMA 180 and ICAM-1 were
      decreased on COV413b cells. This cell line-dependent decrease might be caused by
      differences in glycosylation. We conclude that trypsin/EDTA can be used for rapid
      monolayer cell detachment with high cell yields and limited loss of antigenic
      determinants tested.

PMID- 7736873
TI  - Treatment of benign anal disease with topical nitroglycerin.
AB  - PURPOSE: Fissure-in-ano and acutely thrombosed external hemorrhoids are common,
      benign anal conditions, usually characterized by severe anal pain. Internal anal
      sphincter hypertonia appears to play a role in the etiology of this pain. Nitric
      oxide has recently been identified as the "novel biologic messenger" that
      mediates the anorectal inhibitory reflex in humans. This report documents a
      therapeutic role for nitroglycerin, a nitric oxide donor, in the treatment of
      acutely thrombosed external hemorrhoids and anal fissure. METHODS: Five patients
      with thrombosed external hemorrhoids and fifteen patients with anal fissure or
      ulcer were identified. A treatment regimen that included 0.5 percent
      nitroglycerin ointment applied topically to the anus was instituted. After one
      week of therapy, all patients were re-examined and questioned regarding pain
      relief and side effects of treatment. Fissure patients were followed for eight
      weeks or until healing occurred. RESULTS: All patients reported dramatic relief
      of anal pain following application of nitroglycerin. Pain relief lasted from two
      to six hours. Complete healing of fissures occurred within two weeks in ten
      patients and within one month in two patients. One patient, whose fissure had not
      healed completely within two weeks requested surgical sphincterotomy. Two
      patients remained with persistent anal ulcers despite two months of therapy.
      Both, however, were pain-free. Side effects were limited to transient headache in
      7 of 20 patients. CONCLUSION: Topically applied nitroglycerin ointment appears to
      have a therapeutic role in the treatment of thrombosed external hemorrhoids and
      anal fissure.

PMID- 7736874
TI  - State of the defunctionalized sphincter in patients undergoing ileoanal pouch
      anastomosis.
AB  - PURPOSE: Our aim was to determine manometric status and functional outcome of the
      ileoanal pouch procedure in a subset of patients with defunctionalized anal
      sphincters as a result of long-term fecal diversion. METHODS: The anal manometric
      profiles of 12 patients defunctionalized for one year or more were compared with
      26 patients with nondefunctionalized anal sphincters. Functional data were
      obtained from the Lahey Clinic Ileoanal Pouch Registry. RESULTS: Preoperative
      manometric data revealed a mean resting pressure of 91.5 mmHg in the
      nondefunctionalized group vs. 68.7 mmHg in the defunctionalized group; mean
      squeezing pressure was 171.7 mmHg (nondefunctionalized group) vs. 102.3 mmHg
      (defunctionalized group); and squeezing pressure volume was 1,283,000 mmHg3
      (nondefunctionalized group) vs. 585,000 mmHg3 (defunctionalized group).
      Functionally both groups had a mean of 6.1 bowel movements in a 24-hour period
      and could defer defecation for a mean of 2 hours. Leakage occurred in 22 percent
      of the defunctionalized group and 17 percent of the nondefunctionalized group (P
      = 0.35). CONCLUSION: Despite physiologic perturbations, the long-term,
      defunctionalized anal sphincter can adequately support a restorative procedure
      without regard to timing of pouch creation.

PMID- 7736875
TI  - Expression of proliferation-specific genes in the mucosa adjacent to colon
      carcinoma.
AB  - BACKGROUND: One of the main concerns in colon carcinoma therapy is local
      recurrence of the malignancy at the site of resection. Previous studies have
      shown that morphologically normal-appearing mucosa adjacent to colon carcinoma is
      different from mucosa distant from carcinoma. Mucosa adjacent to a carcinoma is
      characterized by crypt lengthening, cell hypertrophy, and change in production of
      mucopolysaccharides from sulfomucin in normal mucosa to sialomucins in carcinomas
      and adjacent mucosa. Recently there have been reports suggesting that there is an
      upward extension of the proliferative compartment in colonic crypts of this
      adjacent mucosa. METHODS: Immunoblot analysis using antibodies to retinoblastoma,
      statin, c-Fos, c-Jun, and Cdc-2 proteins was used for our study on the expression
      of early cell cycle genes in carcinoma and its adjacent mucosa. In all, 15 tissue
      samples obtained from patients with colon carcinoma were analyzed. Tissue
      specimens were collected and immediately dissected as tumor, 0 to 1, 1 to 2, 2 to
      3, 3 to 4, and 4 to 5 cm from the primary lesion. Dissected pieces were
      homogenized separately and subjected to immunoblot analysis. RESULTS: We found
      upregulation of c-Fos, c-Jun, and Cdc-2 expression in carcinoma and adjacent
      mucosa up to 4 cm from the edge of the carcinoma. The phosphorylated form of
      retinoblastoma is present in the carcinoma as well as in adjacent mucosa up to 4
      cm from the margin of the carcinoma. Furthermore, we observed that the level of
      statin, a nonproliferation-specific nuclear protein, is very low in the primary
      lesion and in adjacent mucosa up to 3 cm. CONCLUSIONS: These results indicate
      that adjacent tissue up to 3 to 4 cm from the carcinoma has elevated levels of
      expression for cell cycle traverse-associated genes and down-regulation of
      nonproliferation-specific gene expressions such as statin. This imbalance
      indicates that within 3 to 4 cm from the edge of the carcinoma, colonic
      epithelial cells are already abnormal and may be in the hyperproliferative and
      preneoplastic state, susceptible to further steps leading to eventual malignant
      transformation.

PMID- 7736876
TI  - Defecographic evaluation of dynamic graciloplasty for fecal incontinence.
AB  - PURPOSE: A prospective defecographic study was performed to evaluate the
      anorectal physiology of dynamic graciloplasty (gracilis muscle transposition and
      subsequent implantation of an electric stimulator) for treatment of fecal
      incontinence. METHODS: From November 1986 until May 1993, 38 consecutive patients
      with incapacitating fecal incontinence were treated with "anal dynamic
      graciloplasty." Defecography was performed before and after surgical procedures.
      Defecographic data (anorectal angle, perineal descent, anal canal length, anal
      canal width, and anal leakage) were correlated with respect to clinical outcome
      and anal manometry. RESULTS: Fecal continence was achieved in 24 patients, which
      correlated significantly with no leakage of barium contrast during defecography
      (P < 0.01, Kruskal-Wallis one-way analysis of variance). In addition, minimum
      anal canal width decreased from 7 mm before surgery to 1 mm after dynamic
      graciloplasty (P < 0.01, paired Student's t-test). CONCLUSION: Defecography is an
      efficient method to evaluate dynamic graciloplasty for fecal incontinence.

PMID- 7736877
TI  - Cyclosporine for the treatment of fulminant ulcerative colitis in children.
      Immediate response, long-term results, and impact on surgery.
AB  - PURPOSE: Emergency surgery for fulminant colitis is often complicated by high
      dose steroid therapy, poor nutrition, and psychologic maladjustment. Cyclosporine
      is effective for fulminant ulcerative colitis in adults, resulting in avoidance
      of immediate surgery in 75 percent of patients and a 55 percent long-term
      remission rate. Over the last five years, we studied the effectiveness of
      cyclosporine in children with fulminant colitis. METHODS: Fourteen patients with
      ulcerative colitis (age, 7-20 years) received cyclosporine after satisfying the
      following criteria: 1) greater than five bloody diarrheal stools per day; 2)
      severe abdominal pain; 3) no improvement after ten days of bowel rest, 4)
      intravenous methylprednisolone (1-2 mg/kg/day); and 5) parenteral nutrition.
      Treatment was begun with oral cyclosporine (4.6-9.6 mg/kg/day), and the dose was
      adjusted to achieve whole blood trough levels measured with a monoclonal
      radioimmunoassay between 150 and 300 ng/ml. If improved, patients were discharged
      on oral cyclosporine, prednisone, and a regular diet. RESULTS: Eleven of 14
      patients (78 percent) responded within two to nine days and were able to consume
      a normal diet, had three or less soft stools per day, and had no pain. One did
      not respond after ten days and underwent an ileal pouch-anal anastomosis
      procedure. Two patients elected surgery after 20 days of therapy and a partial
      response. Of 11 patients who left the hospital, 4 had recurrent symptoms after 2
      to 11 months of taking therapeutic doses of cyclosporine and 3 flare ups while
      weaning from cyclosporine after 4 to 8 months. Three patients have been weaned
      from cyclosporine after 8 to 13 months and have remained in remission from six
      months to five years. One patient is about to complete a six-month course of
      cyclosporine. Overall ten (72 percent) have undergone surgery, including 7 of 11
      who responded initially to cyclosporine and left the hospital. Weight (P <
      0.001), albumin (P < 0.01), erythrocyte sedimentation rate (P > 0.05), and
      prednisone dose (P < 0.001) improved significantly in the seven patients on
      cyclosporine who responded initially, left the hospital, and subsequently
      underwent surgery. CONCLUSIONS: Cyclosporine is effective in achieving clinical
      remission in 80 percent of children with refractory fulminant colitis; however,
      within one year, most initial responders will require colectomy because of a
      flare up of the disease. In a majority of patients, the role of cyclosporine
      therapy is to rapidly ameliorate symptoms and prevent precipitous colectomy,
      improve nutrition and psychologic adaptation, and reduce the steroid dose leading
      to surgery in a well-prepared patient.

PMID- 7736878
TI  - Postoperative morbidity and mortality following resection of the colon and rectum
      for cancer.
AB  - PURPOSE: The aim of this study was to report the prevalence of postoperative
      complications and mortality of patients with colorectal cancer when treated by
      conventional surgery. METHODS: Morbidity and mortality following open resection
      for colorectal cancer were analyzed in 1,846 patients whose clinical, operative,
      and pathology data were prospectively documented over a 20-year period. RESULTS:
      Mortality following elective resection of the left and right colon was low,
      whereas overall morbidity was high (37.2 percent). Respiratory and cardiac
      complications were especially common. Incidence of clinically significant leakage
      was similar following right (0.5 percent) or left (1.1 percent) hemicolectomy.
      Incidence of anastomotic leakage was significantly higher after emergency right
      hemicolectomy (4.3 percent). Overall morbidity following excision of the rectum
      was high (40.2 percent). Respiratory and cardiac complications predominated.
      Incidence of clinically significant anastomotic leakage following anterior
      resection was low (2.9 percent). Over the years, there has been a decline in the
      number of patients with tumor demonstrated histologically in a line of resection,
      suggesting an improved local surgical clearance. CONCLUSIONS: These results
      following conventional surgery may be useful when evaluating new techniques.

PMID- 7736879
TI  - Acute pouchitis and deficiencies of fuel.
AB  - PURPOSE: Acute pouchitis is a troublesome complication after restorative
      proctocolectomy. Deficiency of fuel, especially short chain fatty acids (SCFA),
      produced by anaerobic bacterial fermentation of saccharides, is implicated in
      ulcerative and diversion colitis. Our hypothesis was that SCFA deficiency occurs
      in acute pouchitis, and correction of the deficiency is associated with
      resolution of pouchitis. METHODS: Thirty-two patients were studied, 10 with
      histologically confirmed acute pouchitis and 22 with healthy pouches. Stool
      concentrations of SCFA (acetic, propionic, butyric, and valeric acids) were
      determined by gas-liquid chromatography. Quantitative bacteriologic studies of
      stool were carried out, and four-quadrant pouch biopsies were assessed by a
      pathologist who was unaware of the clinical state. Patients with pouchitis were
      treated for six weeks with metronidazole and given dietary advice to increase
      their intake of fermentable saccharides. RESULTS: Stool concentrations of SCFA
      were significantly less in pouchitis patients compared with patients with healthy
      pouches (340 mumol/g (range, 124-492) vs. 93 (range, 44-136) P < 0.01). No
      differences in anaerobic or aerobic counts were seen. Resolution of pouchitis was
      associated with a significant increase in SCFA, but anaerobic counts fell.
      CONCLUSION: Deficiency of SCFA is implicated in acute pouchitis.

PMID- 7736880
TI  - Role of laparoscopy in colorectal surgery. A prospective evaluation of 200 cases.
AB  - PURPOSE: The aim of this study was to prospectively evaluate the role of
      laparoscopic-assisted surgery in patients presenting for routine colorectal
      surgical procedures. METHODS: Two hundred consecutive patients were assessed for
      the possible use of laparoscopic surgery. The decision regarding suitability of
      the patient for the procedure was made by the operator. For the purpose of
      analysis, patients were assigned to open, converted, and laparoscopic groups.
      RESULTS: Ninety-five of 200 patients were considered appropriate for laparoscopic
      surgery, 62 (65.3 percent) being successfully completed. These completed
      operations included right colectomy (24/30), sigmoid colectomy (22/36),
      appendectomy (9/10), anterior resection (3/8), abdominoperineal resection (3/5),
      and left colectomy (1/2). Complications attributable to laparoscopy were
      infrequent (6.3 percent) and were not responsible for any deaths. Patients in the
      laparoscopic group required less analgesia, tolerated oral intake earlier, and
      were discharged from the hospital earlier than those who were converted or who
      had open procedures. CONCLUSIONS: Laparoscopic-assisted surgery is safe,
      effective, and applicable to many of the standard colorectal procedures. Observed
      benefits include less postoperative pain and shorter hospital stay.

PMID- 7736881
TI  - Anorectal manovolumetry in the diagnosis of fecal incontinence.
AB  - PURPOSE: This study was designed to investigate rectal reservoir function and
      anal pressures in patients with fecal incontinence using anorectal manovolumetry
      and to evaluate the reproducibility of the investigation. METHODS: Forty-eight
      patients with fecal incontinence were investigated with respect to anal pressures
      and rectal volume changes and sensibility in response to stepwise increased
      rectal pressures (5-60 cm of H2O). Patients with known rectal wall diseases were
      excluded. Results were compared with those of 25 control subjects investigated in
      a similar manner. In ten individuals in the latter group, investigation was
      repeated after 5 minutes and 24 hours. RESULTS: Resting pressure (RP), squeezing
      pressure (SP), and the difference between SP and RP was lower in patients than in
      controls (P < 0.0001). There was no significant difference between patients and
      controls concerning rectal sensibility or compliance (P > 0.05), but there was a
      correlation between RP and rectal compliance (r = 0.25; P < 0.05) and between SP
      and rectal compliance (r = 0.30; P < 0.01). There was good reproducibility of RP
      and SP after five minutes (r = 0.88-0.92; P < 0.001). The day-to-day variation
      was larger for RP (r = 0.52; P > 0.05) compared with SP (r = 0.89; P < 0.001).
      Rectal compliance at 40 cm of H2O was reproducible after 5 minutes (r = 0.98; P <
      0.0001) and 24 hours (r = 0.88; P < 0.01). CONCLUSIONS: These results indicate
      that the primary defect in incontinent patients is a sphincter dysfunction. Any
      reduction in rectal compliance is likely to be a secondary phenomenon.

PMID- 7736882
TI  - Immunohistochemical study of the colonic muscle and innervation in idiopathic
      chronic constipation.
AB  - PURPOSE: This study was designed to investigate neural and muscular features of
      the colonic wall in patients with severe idiopathic constipation. METHODS: By
      using quantitative immunohistochemistry, resected specimens from 14 patients with
      idiopathic chronic constipation and 17 nonobstructed cancer controls were
      studied. RESULTS: Routine histology revealed no significant histologic
      abnormality throughout the colon apart from four cases of melanosis coli. Ratio
      of the thickness of circular to longitudinal muscle was significantly lower in
      the left colon in constipated subjects. The myenteric plexus appeared
      morphologically normal in all subjects. S-100 protein, which stains neuronal
      supporting tissues, demonstrated an increase in the proportion of neural tissue
      in the myenteric plexus. There was an increased number of PGP-9.5 immunoreactive
      nerve fibers in the muscularis propria in constipated patients, and this was
      significantly higher in the ascending and descending colon. CONCLUSION:
      Intractably constipated patients have alterations in the neural composition of
      the colonic myenteric plexus and innervation of the circular muscle.

PMID- 7736883
TI  - Cimetidine as an adjuvant treatment in colorectal cancer. A double-blind,
      randomized pilot study.
AB  - PURPOSE: To evaluate the influence of a H2 receptor antagonist (cimetidine) on
      survival in patients with colorectal carcinoma, a randomized, controlled pilot
      study was performed in three university hospitals in Copenhagen, Denmark.
      METHODS: A total of 192 patients, who had undergone a resection or an exploratory
      operation for adenocarcinoma of the colon or rectum between May 1988 and May
      1991, were enrolled in the study. After a median observation time of 40 months,
      outcome was noted for each patient concerning cancer-specific mortality rate.
      RESULTS: In patients operated with curative intent (n = 148), no difference was
      found in cancer-specific mortality between the two treatments. However, a
      tendency toward reduction in mortality rate was found in patients with curatively
      operated Dukes Stage C carcinoma (P = 0.11, log-rank test; difference, 29
      percent; 90 percent confidence interval, 2 to 57 percent) in the cimetidine
      treated group. In patients with disseminated disease no total difference was
      found between the two treatment groups. CONCLUSIONS: Cimetidine does not seem to
      reduce mortality in patients with colorectal cancer, but there seems to be a
      tendency toward a survival benefit in patients undergoing surgery for Dukes Stage
      C carcinoma. Results seem to justify trials in this patient category to reveal a
      benefit of H2 receptor antagonists in adjuvant therapy of colorectal carcinoma.

PMID- 7736884
TI  - Butyrate absorption and lactate secretion in ulcerative colitis.
AB  - PURPOSE: Fecal electrolytes and organic anion concentrations are altered in
      ulcerative colitis, presumably reflecting changes in colon epithelial transport.
      Information of mucosal absorption of butyrate in active ulcerative
      proctosigmoiditis is not available. METHODS: Dialysis bags containing 70
      mmol/liter of butyrate in an isotonic electrolyte solution were placed in the
      rectum for 30 minutes. Net absorption or secretion rates of butyrate, lactate,
      and electrolytes were determined in the rectum of 12 patients with active
      ulcerative colitis (UC) and in 10 patients with quiescent UC and then compared
      with 10 healthy controls. RESULTS: Net flux rates demonstrated a considerable
      absorption of butyrate in patients with active inflammation of 7.5 +/- 0.4
      mumol/cm2/h and quiescent colitis of 6.6 +/- 0.4 mumol/cm2/h, equal to absorption
      in healthy controls of 6.3 +/- 0.5 mumol/cm2/h, P = 0.12. Despite normal butyrate
      absorption, sodium absorption was compromised in active ulcerative colitis (11.5
      +/- 1.4 mumol/cm2/h) compared with quiescent (15.4 +/- 1.0 mumol/cm2/h) and
      controls (18.7 +/- 0.8 mumol/cm2/h) (P = 0.0006). Mucosal secretion of L-lactate
      was minimal in both healthy controls and quiescent UC but significantly increased
      in patients with proctosigmoiditis (0.2 +/- 0.1 mumol/cm2/h, 0.2 +/- 0.1
      mumol/cm2/h vs. 0.9 +/- 0.2 mumol/cm2/h; P = 0.0001). Appearance of D-lactate was
      negligible in all three groups. CONCLUSIONS: This study demonstrates that rectal
      butyrate absorption is normal in UC, and it follows that butyrate supplied in
      enemas can be expected to be absorbed. The inflamed colonic mucosa secretes L
      lactate, and the increased fecal lactate concentrations can be explained by
      mucosal origin of lactate.

PMID- 7736885
TI  - Reduction in tissue blood flow in J-shaped pelvic ileal reservoirs.
AB  - PURPOSE: This study sought to evaluate tissue blood flow during J-shaped ileal
      reservoir construction. METHODS: Using laser Doppler flowmetry, tissue blood flow
      was measured at various locations in J-shaped ileal reservoirs constructed in 10
      dogs before pouch-anal anastomosis. For 12 weeks postoperatively, animals were
      assessed for clinical complications. In another five dogs, tissue blood flow was
      measured at various stages of J-pouch construction. RESULTS: Tissue blood flow in
      the reservoir was reduced and was lowest at the "apex" of the "J", the site of
      clinical stricture in one animal. During reservoir construction, longitudinal
      enterotomy was associated with the greatest reduction in tissue blood flow.
      Lowest blood flow in the reservoir was at the site of the intended pouch-anal
      anastomosis (11.5 +/- 1.6 ml/100 g/min vs. 43.4 +/- 3.4 ml/100 g/min (controls);
      P < 0.05). CONCLUSIONS: Operative maneuvers of J-shaped ileal reservoir
      construction, particularly longitudinal enterotomy, significantly reduce tissue
      perfusion in the involved bowel segment. Tissue blood flow in the pouch is lowest
      at the site of intended pouch-anal anastomosis, and this may contribute to
      development of complications seen clinically.

PMID- 7736886
TI  - Cecostomy. Therapeutic indications and results.
AB  - PURPOSE: The role and effectiveness of catheter tube cecostomy as a means of
      colonic decompression are not clearly defined. Our aim was to clarify the
      clinical indications, functional performance, and concomitant morbidity
      associated with tube cecostomy. METHOD: This was a retrospective chart review of
      patients receiving catheter tube cecostomy at the Mayo Clinic over an 11-year
      period. RESULTS: Sixty-seven patients (median age, 69 years) had catheter tube
      cecostomy placement. Clinical indications for tube cecostomy were colonic pseudo
      obstruction, distal colonic obstruction, cecal perforation, cecal volvulus,
      preanastomotic decompression, and miscellaneous usage. Operation was emergent in
      43 (64 percent) patients and elective in 24 (36 percent) patients. Tube cecostomy
      was the primary procedure in 47 (70 percent) patients and complimentary in 20 (30
      percent) patients. Minor complications were seen in 30 patients (45 percent),
      including pericatheter leak, superficial wound infection, tube occlusion, skin
      excoriation, premature tube dislodgement, colocutaneous fistula, and ventral
      hernia. No patient required reoperation for tube-related morbidity. CONCLUSIONS:
      Catheter tube cecostomy is of therapeutic value in select clinical situations
      including refractory colonic pseudo-obstruction, cecal volvulus, cecal
      perforation, or distal colonic obstruction. Proper patient selection, careful
      tube placement, and vigilant postoperative tube care should provide adequate
      function with minimal morbidity.

PMID- 7736887
TI  - Superior mesenteric artery syndrome as a complication of ileal pouch-anal
      anastomosis. Report of a case.
AB  - PURPOSE: Duodenal compression by the superior mesenteric artery following total
      proctocolectomy and ileal pouch-anal anastomosis is a rare occurrence. Previous
      surgical treatment involved duodenal division. The aim of this report was to
      describe a case with such a complication and to discuss an operative alternative.
      METHODS: Case report. RESULTS: Mobilization of the duodenum from its
      retroperitoneal attachments, without transection and reanastomosis, allowed the
      free passage of gas through the duodenum and recovery for the patient.
      CONCLUSION: This case report suggests that a more conservative approach may be
      successful in managing this complication.

PMID- 7736888
TI  - Ulcerative colitis: rectal dilations in a patient with refractory diarrhea.
      Report of a case.
AB  - A 45-year-old man with an eight-year history of ulcerative colitis was evaluated
      for severe, nonbloody diarrhea. Symptoms, which began two years earlier, were
      characterized by 15 bowel movements per day, accompanied by urgency and
      incontinence. A reduced rectal compliance was measured at manometry. All
      conventional treatments were not able to modify the symptoms despite improvement
      of inflammatory colonic lesions. PURPOSE: The aim was to reduce bowel movements
      and incontinence by increasing rectal compliance. METHODS: Gradual pneumatic
      dilations of the rectum were performed three times per week for three weeks.
      RESULTS: The patient's diarrhea improved dramatically, decreasing in frequency
      from approximately 15 to only 3 bowel movements per day, while contemporaneously
      increasing rectal compliance. Such effect, still evident 15 months after
      discontinuation of dilation, was probably obtained by improvement of viscoelastic
      features of the intestinal wall. CONCLUSIONS: Rectal pneumatic dilation may be a
      successful attempt in some forms of intractable diarrhea in long-lasting
      ulcerative colitis.

PMID- 7736889
TI  - Laparoscopic-assisted colectomy and lymphadenectomy without peritoneal
      insufflation for sigmoid colon cancer patients.
AB  - PURPOSE: A new method for laparoscopic-assisted sigmoid colectomy and
      lymphadenectomy is presented. The purpose of this method is to avoid
      complications and restrictions associated with pneumoperitoneum. METHODS:
      Abdominal wall is lifted up with Kirschner wires, which are placed in the middle
      and left lower abdomen; then a minilaparotomy, which can be created because air
      tightness is not necessary, is extended at the beginning of the operation to
      later remove the resected specimen. Two laparoscopic instruments are inserted
      through the right lower abdomen. Through the minilaparotomy, the surgeon can
      operate with conventional instruments. RESULTS: Operative time can be shortened,
      and surgical manipulations such as ligations and sutures are far easier than and
      cosmetic results are similar to those of laparoscopic surgery under
      pneumoperitoneum. CONCLUSION: We believe that this technique is a safe, time
      saving, and cost-beneficial technique for sigmoid colectomy, and by changing the
      location of the minilaparotomy, this method can also be applied to other types of
      gastrointestinal surgery.

PMID- 7736890
TI  - Anoscopic-assisted insertion of end-to-end anastomosing staplers.
AB  - Widespread popularity of the double-stapler technique has created the potential
      for anal sphincter and anal canal injury during transanal insertion of the end-to
      end anastomosing stapler. The Faensler operating anoscope helps eliminate that
      potential by symmetrically dilating the anal canal, thereby permitting atraumatic
      insertion of the end-to-end anastomosing stapler.

PMID- 7736891
TI  - Riddle of the sphincters in anal fissure.

PMID- 7736892
TI  - Relationship between colorectal and prostate cancer.

PMID- 7736893
TI  - Use of transdermal fentanyl.

PMID- 7736894
TI  - Recognition, assessment, and treatment of anxiety in the critical care patient.
AB  - A multidisciplinary group of experts involved in the treatment of critically ill
      patients participated in a workshop conference designed to develop practice
      recommendations for the recognition, assessment, and treatment of anxiety in the
      critical care environment. Anxiety was identified as a ubiquitous problem in
      critical care that may interfere with healing and recovery. The faculty agreed
      that clinicians should be familiar with the signs and symptoms of anxiety and
      should be able to determine when interventions are necessary. Whenever possible,
      nonpharmacologic methods for anxiolysis should be incorporated into intensive
      care protocols. Intensive care personnel should be trained in those interventions
      that require specialized expertise, and they should become familiar with the
      drugs available for the treatment of anxiety. Protocols for determining the best
      agents to be used in a given setting and their most appropriate method of
      administration should be established. Pharmacologic and nonpharmacologic
      treatments are not mutually exclusive but should be complementary. Finally,
      procedures for obtaining psychiatric consultation, when necessary, should be in
      place.

PMID- 7736895
TI  - Islet cell antibodies (ICA), insulin autoantibodies (IAA), islet cell surface
      antibodies (ICSA) and C-peptide in 1031 school children in a population with a
      high background incidence of IDDM.
AB  - Islet cell antibodies (ICA), insulin autoantibodies (IAA) and islet cell surface
      antibodies (ICSA) together with C-peptide were determined in 1031 healthy
      schoolchildren to evaluate the frequency of autoimmune reactions towards
      endocrine pancreas and its relation to insulin secretion in non-diabetic
      children. The prevalence of ICA (levels > 6 JDF units) was 1.4% (14/1012) while
      44 children (4.3%) were ICSA-positive and 40 (4%) had IAA. Girls had higher
      titres of ICSA than boys. Young children (7-8 years) more often had IAA than 12
      13-year-old children who, however, had ICA three times more often than the young
      children. There were no clear associations between the different antibodies. Of
      the children, 2.4% had very low post-prandial serum C-peptide values (< or = 0.25
      nmol/l). Serum C-peptide was higher in girls than in boys (P < 0.001) and in
      older children than in younger (P < 0.001). Girls with low levels of ICA had high
      C-peptide values, while girls with high ICA titers had low C-peptide values, the
      latter perhaps indicating partial beta cell loss. IAA and ICSA were not related
      to C-peptide values but both positive ICSA and high C-peptide values were most
      common in the autumn (P < 0.02 and P < 0.0001, respectively). One of the ICA
      positive children developed diabetes in 1991, 4 years after the blood sample was
      taken. Since after 5 years only one of the children has developed IDDM, it can be
      concluded autoimmune reactions towards endocrine pancreas and insulin may occur
      in many children without the development of manifest diabetes. Those with high
      ICA titers may have lost so many beta cells that their insulin secretion is
      affected, which in some cases might lead to diabetes many years later.

PMID- 7736896
TI  - Reciprocal changes in left ventricular collagen alpha 1 chain gene expression
      between types I and IV in spontaneously diabetic rats.
AB  - The characteristic features of diabetic cardiomyopathy have been reported to be
      increased collagen formation associated with impairment of ventricular
      performance, based on experimental models of diabetes. The present study was
      therefore designed to clarify collagen gene expression in hearts obtained from
      female spontaneously diabetic BioBreeding Worcester Tokyo (BB/W@Tky) rats.
      Cardiac hypertrophy was observed as early as 14 weeks in diabetic BB/W@Tky rats,
      i.e. 4 weeks after the onset of diabetes. Left ventricular gene expression of
      collagen alpha 1 (I) was decreased to 10.6% of the control level. In 24-week-old
      diabetic rats, which had more marked cardiac hypertrophy, the level of alpha 1
      Type I collagen mRNA was further decreased to 5.7% of the control level, whereas
      collagen alpha 1 (IV) mRNA demonstrated a 3-fold increase. As a result, a ratio
      of collagen alpha 1 (IV) to actin mRNA was positively correlated with plasma
      glucose concentration. These results suggest that hyperglycemia may alter the
      gene expression of extracellular matrix proteins, resulting in the morphological
      and functional changes seen in diabetic cardiomyopathy.

PMID- 7736897
TI  - Molecular analysis of insulin receptor gene in Werner's syndrome.
AB  - Werner's syndrome is characterized by premature aging and frequent impaired
      glucose tolerance or overt diabetes. Insulin resistance may play an important
      role and may be caused by a post-receptor defect or dysfunctional insulin
      receptor. The present study was undertaken to investigate the insulin receptor
      gene mutation in Werner's syndrome. The genomic DNAs were obtained from four
      patients with Werner's syndrome. Exons 2-22 of the insulin receptor gene except
      exon 1 were amplified from genomic DNA by the polymerase chain reaction and
      screened for nucleotide variation by examining for single-stranded conformational
      polymorphisms. There were no nucleotide variations in exons 2, 4-->7, 9 and 12-
      >22. Variants were thus found in exons 3, 8, 10 and 11 and each were sequenced.
      The variant in exon 8 was due to a silent polymorphism (GAT-->GAC/T, Asp519) and
      other variants in exons 3, 10 and 11 were caused by nucleotide substitutions in
      introns. These results suggest that the patients with Werner's syndrome express
      normal insulin receptors and that the primary genetic lesion for insulin
      resistance is not in the insulin receptor gene. Insulin resistance in Werner's
      syndrome is thus likely by a post-receptor defect.

PMID- 7736898
TI  - A glimpse of the 'natural history' of established type 2 (non-insulin dependent)
      diabetes mellitus from the spectrum of metabolic and hormonal responses to a
      mixed meal at the time of diagnosis.
AB  - The reported glucose and immunoreactive insulin (IRI) responses to oral and
      intravenous glucose in subjects with Type 2 diabetes have not always been
      consistent. This may have resulted from variations in the method of glucose
      administration, the ethnic backgrounds of subjects, the diagnostic criteria
      applied, the duration of the disease or IRI assay methods. The use of a mixed
      meal rather than glucose has been shown to provide a more physiological stimulus
      to the pancreatic beta-cell due to both glucose and non-glucose secretagogues. We
      have analysed the metabolic and hormonal responses of 188 newly diagnosed
      Caucasian subjects with Type 2 diabetes and 38 non-diabetic subjects to a 500
      kcal mixed meal. The diabetic subjects were stratified according to fasting
      plasma glucose (FPG) (< 9, 9-12, 12-15 and > or = 15 mmol/l) and body mass index
      (BMI) (< 26.5, 26.5-30 and > or = 30 kg/m2). Increasing FPG was associated with
      higher peak glucose concentrations and increasing failure to achieve basal
      glucose levels by 4 h. Median fasting IRI concentrations were similar to those of
      normal subjects, but all diabetic subjects had reduced early-phase insulin
      secretion. Diabetic subjects with FPG < 9 mmol/l showed augmented IRI area under
      the curve (AUC) at 2 and 4 h, whereas those with FPG > 9 mmol/l had progressive
      falls in IRI AUC to below that of the normal subjects (P < 0.0001 for the trend).
      Peak IRI concentrations declined progressively with increasing FPG. Despite
      equivalent glucose exposure simple trends of increasing AUC, IRI with increasing
      BMI were statistically significant (P < 0.001, P < 0.02, P < 0.001 and P < 0.01,
      respectively for each FPG group). Both fasting and AUC non-esterified fatty acid
      concentrations increased significantly with FPG regardless of BMI (P < 0.001 for
      the trends). These results using a more physiological mixed meal challenge in a
      large number of recently diagnosed Type 2 diabetic subjects demonstrate a marked
      and increasing loss of beta-cell secretory function with increasing fasting
      hyperglycaemia aggravated by insulin resistance with increasing obesity.

PMID- 7736899
TI  - Comparison of three methods for the quantification of beta-cell function and
      insulin sensitivity.
AB  - The purpose of this study was to compare two techniques for the quantification of
      beta-cell function and insulin sensitivity. Sixteen subjects (2 with newly
      diagnosed non-insulin-dependent diabetes mellitus, 8 with impaired glucose
      tolerance (IGT) and 6 with normal glucose tolerance (NGT)), aged 40-65 years
      underwent an oral glucose tolerance test (OGTT), a continuous infusion of glucose
      with model assessment (CIGMA) and a hyperglycaemic clamp (10 mmol/l) in random
      order. As measures of beta-cell function we used the clamp derived area under the
      curve from 0-10 min (first phase insulin response) and the mean insulin level
      during the last 20 min of the clamp (second phase insulin response). Insulin
      sensitivity was reflected by the ratio of the glucose infusion rate and the mean
      insulin level during the last 20 min of the clamp (M/I ratio). Measures for beta
      cell function and insulin sensitivity derived from OGTT and CIGMA appeared to
      correlate only moderately (0.5-0.7) with the corresponding clamp measures. It is
      concluded that OGTT and CIGMA derived measures of beta-cell function and insulin
      sensitivity should be interpreted with caution.

PMID- 7736900
TI  - Management of type 2 diabetes in Western Australian metropolitan general
      practice.
AB  - The purpose of this study was: (1) to record GP opinions, practices and outcomes
      for the care of Type 2 Diabetes Mellitus (DM2), (2) compare practice facilities
      and process of care with a criterion of recommended competent care and (3)
      determine if there were any differences between vocationally registered and non
      vocationally registered GPs. A random sample of 204 metropolitan doctors from 124
      practices was selected and an audit performed on 467 of their patient records.
      GPs pursued good blood sugar control and advocated lifestyle changes before
      hypoglycaemic drugs. Over 80% regard uncomplicated DM2 as a condition for general
      practice management. However, only 15% conducted an annual diabetes check, 9% had
      a diabetic register, 6% a diabetic recall system and 8% used a diabetic health
      care checklist for monitoring their patients. The most commonly recorded
      processes of medical audit in the previous 12 months were: blood pressure (94%),
      duration of diabetes (72%), blood glucose (70%), diet (66%), body weight (56%),
      HBA1c (52%) and ophthalmoscopy (50%). The least commonly recorded processes of
      care were body mass index (5%), inspection of the feet (18%), enquiries about
      vaginitis or impotence (23%). The amount of exercise, alcohol and tobacco was
      recorded in only 34% of records. Hypoglycaemic drugs were used appropriately but
      the most commonly used drugs for treating hypertension in DM2 patients were
      thiazide diuretics and beta-blockers. Vocationally registered (VR) doctors had
      better records, higher process of care scores and more were willing to
      participate in the study than non-vocationally registered (NVR) doctors. However,
      there was no difference in metabolic control between patients from either group.
      The use of a Diabetic Health Care Checklist would improve diabetes care
      especially in the search for early complications and in the recording of HBA1c
      and other metabolic parameters. The drugs commonly used to control hypertension
      can have adverse effects on glucose and lipid metabolism and should be replaced
      with glucose and lipid neutral drugs.

PMID- 7736901
TI  - Rhabdomyolysis in diabetic emergencies.
AB  - Rhabdomyolysis (RM) is a clinical and laboratory syndrome resulting from leakage
      of muscle cell contents into plasma. The increased plasma concentration of the
      substances released such as creatine kinase (CK) permits the clinician to
      diagnose this syndrome. Non-traumatic RM has occasionally been reported in
      patients with diabetic decompensation. We encountered about 44 cases of RM in 265
      diabetic emergencies (including DKA or hyperosmolar, or both) during the period
      from 1984-1 to 1990-6, diagnosed based on (1) serum creatine kinase (CK) > 1000
      IU/l and (2) the absence of acute myocardial infarction, stroke and end-stage
      renal disease. On admission, those who presented with RM had significantly higher
      concentration of blood urine nitrogen (BUN) (83.3 +/- 5.9 vs. 58.8 +/- 2.4 mg/dl,
      P < 0.05), creatine (4.45 +/- 0.4 vs. 2.97 +/- 0.1 mg/dl, P < 0.05) and serum
      osmolarity (386.5 +/- 5.2 vs. 351.6 +/- 2.4 mOsm/kg, P < 0.05). The mortality
      within 1 week of diabetic emergencies (38.5% for DKA, 35.5% for HHNK) was higher
      in patients with RM than those without RM (9.7% for DKA, 26.7% for HHNK). There
      was a correlation (r = 0.49, P < 0.05) between the levels of serum creatinine and
      CK in patients with RM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736902
TI  - Acarbose and nutrient intake in non-insulin dependent diabetes mellitus.
AB  - We carried out a double-blind, placebo-controlled cross-over trial to evaluate
      changes in nutrient intake during acarbose therapy and short-term changes in
      metabolic control in Finnish patients with non-insulin dependent diabetes
      mellitus. The efficacy and tolerability of acarbose was also assessed during this
      short 8-week treatment period. Patients were treated either with diet only (18
      subjects) or with diet and sulphonylurea (9 subjects) prior to entering this
      trial. The nutrient intake was assessed using food records kept during the last 2
      5 days of each treatment period. Treatment with acarbose did not affect body
      weight or the intake of energy and carbohydrates, but it was associated with a
      slight decrease in the dietary fat intake. Both fasting and 2-h postprandial
      blood glucose levels fell continuously during acarbose but the change did not
      reach statistical significance during the 8-week treatment period. The 2-h serum
      insulin response was not affected. The results were similar in patients treated
      with acarbose alone and in those receiving acarbose together with sulphonylurea
      regimen. The acarbose regimen was relatively well tolerated although mild
      gastrointestinal side-effects were observed in many patients. In conclusion,
      treatment with acarbose has no major effects on nutrient intake in diabetic
      patients. To monitor changes in metabolic control after the introduction of
      acarbose to the treatment regimen a longer than 8-week period is needed.

PMID- 7736903
TI  - Ten-year incidence (1981-90) of insulin-dependent diabetes in the 0-29-year-old
      age group in Benghazi, Libya.
AB  - The incidence of Type 1 diabetes in Benghazi, Libya in the < 30-years age group
      was prospectively studied during the period 1981-1990. A total of 161 male and
      150 female new cases were diagnosed during the study period. Case ascertainment
      was estimated to be 100%. The overall incidence rate (per 100,000) was 8.8 (95%
      C.I., 7.8-9.9). Rates were 8.9 (95% C.I., 7.6-10.4 among males and 8.6 (95% C.I.,
      7.3-10.1) among females). A female predominance in the 0-14-years age range and a
      male predominance in the 15-29-years age range were observed (P > 0.05). The age
      specific incidence rate increased steadily from 2.2 (95% C.I., 1.4-3.4) in the 0
      4-years age group to 16.9 (95% C.I., 13.6-21.0) in the 15-19-years age group and
      declined afterwards. Age adjusted incidence rates in the 0-14- and 15-29-years
      age ranges were 7.0 (95% C.I., 6.0-8.2) and 11.9 (95% C.I., 10.0-14.0),
      respectively. Yearly variation and seasonality of onset were not significant. The
      study revealed a relatively high incidence rate of Type 1 diabetes among Libyan
      Arabs aged less than 30 years.

PMID- 7736904
TI  - Associated risk factors of diabetes in Kin-Hu, Kinmen.
AB  - This is a community-based survey carried out by the Yang-Ming Crusade to
      investigate potential risk factors of non-insulin-dependent diabetes in Kin-Hu,
      Kinmen. A total of 3236 people completed both questionnaire and venipuncture
      (1536 men and 1700 women). Sex, age, education level, family history, obesity,
      hypertension, triglyceride, cholesterol levels and usage of diuretics were found
      significantly correlated with diabetes in univariate analyses. The stepwise
      logistic regression was used in multivariate analysis. Important correlates were
      age (OR = 1.03; 95% CI, 1.02-1.05), body mass index (OR = 1.96; 95% CI, 1.31
      2.94), waist/hip ratio (OR = 2.08; 95% CI, 1.38-3.13), triglyceride (OR = 1.47;
      95% CI, 1.19-1.81), cholesterol (OR = 1.47; 95% CI, 1.23-1.77), HDL-cholesterol
      (OR = 0.50; 95% CI, 0.25-0.99) and previous hypertension (OR = 1.66; 95% CI, 1.05
      2.61). In addition to body mass index, waist/hip ratio was an independent risk
      factor. Besides the risk factor of total cholesterol, HDL-cholesterol was an
      independent protective factor. Previous history of hypertension was a stronger
      predictor on diabetes than current hypertension.

PMID- 7736905
TI  - Relevance of tissue distribution studies.

PMID- 7736906
TI  - Chiral sulfoxidation of albendazole by the flavin adenine dinucleotide-containing
      and cytochrome P450-dependent monooxygenases from rat liver microsomes.
AB  - The enantioselectivity of the in vitro sulfoxidation of the prochiral drug
      albendazole was investigated in rat liver microsomes. When biological material
      obtained from control rats and phenobarbital-, 3-methylcholanthrene-, or
      dexamethazone-pretreated rats was subjected to specific immunological and
      chemical inhibitors, it was shown that two main enzymatic systems--cytochrome
      P450s and flavin-containing monooxygenase (FMO)--were responsible for the
      sulfoxidation. Purified FMO from rat liver was used to study the
      enantioselectivity of this enzyme in the sulfoxidation of albendazole. The
      enantiospecificity of FMO is the reverse of that of the P450s. Nevertheless, each
      P450 isoenzyme involved in this reaction presents its own individual
      stereoselectivity.

PMID- 7736907
TI  - Kinetics of sequential metabolism. Contribution of parallel, primary metabolic
      pathways to the formation of a common, secondary metabolite.
AB  - Interpretation of rate constants in the sequential metabolism of two different
      primary metabolites (MIA and MIB) for formation of a common, secondary metabolite
      (MII) after drug administration requires theoretical development of formulations
      that govern mass transfer during intravenous and oral administrations. Two cases
      (a and b) were presently considered for metabolism occurring only in the first
      pass organs (intestine and liver) for flow-limited drugs and primary and
      secondary metabolites: (case a) wherein drug formed only the two primary
      metabolites, with the fractions of total body clearance that formed MIA and MIB,
      being denoted by f1 and f2, respectively, and (case b) wherein other additional
      elimination pathways for drug were present. MIA and MIB only partially formed MII
      (denoted by fMIA and fMIB, respectively), because provision was made for
      alternate elimination pathways; the fractional clearance in the formation of MII
      from MIA and MIB were fMIA and fMIB, respectively. Drug was metabolized to MIA
      than MII within the gut lumen with oral drug administration; the MIA and MII
      formed were further absorbed. Triangular matrices were found to result from mass
      transfer equations for first-order conditions with oral and intravenous
      administrations. Upon inversion of the matrices, the areas under the curve for
      drug and metabolite species were obtained after multiplication by the
      administered dose and division by the volume of the species considered. However,
      the dose-corrected area under the curve was used as the basis for comparison.
      Case-independent solutions were obtained for the fractions absorbed (Fa, FaMIA,
      FaMIB) and the availabilities (F, F(MIA), F(MIB)) of drug and the primary
      metabolites, and for f1, f2, f1/f2, fMIA/fMIB, and (f1fMIA)/(f2fMIB) (ratio of
      effective clearances of MII formation from D via MIA and MIB). Case-dependent
      solutions also existed. For case a (f1 + f2 = 1), the fraction of total body
      clearance that formed MIA (f1) or MIB (f2) was solved with the area under the
      curve of MII after intravenous D, MIA, and MIB administrations. For case b,
      however, the same constants were obtained after greater manipulation, and
      entailed oral administration of the metabolites. Although solutions for the
      ratios of f1/f2 and (f1fMIA)/(f2fMIB) were found, the fractional clearances in
      formation of MII from MIA (fMIA) and MIB (fMIB) were, however, not provided in
      both cases unless MII was completely absorbed.

PMID- 7736908
TI  - Effect of intracellular chloride on the cellular pharmacodynamics of cis
      diamminedichloroplatinum(II).
AB  - cis-Diamminedichloroplatinum(II) (DDP) is activated by aquation to species that
      are much more reactive with nucleophiles. The dichloro form of the drug
      predominates at the high CI- concentrations found outside the cell (approximately
      108 mM), whereas the reactive aquated forms predominate at low CI-. Lower CI-
      levels inside cells are presumed to facilitate cellular platination reactions,
      but little actual data are available to support this general belief. We therefore
      determined intracellular CI- in tumor cell lines and assessed the effect of
      modulation of CI- levels on the sensitivity to DDP and the platination of DNA.
      Basal CI- levels were 22.7 +/- 1.5 mM (N = 4) in 2008 human ovarian carcinoma
      cells and 12.2 +/- 2.3 mM (N = 4) in the resistant subline C13*. Intracellular CI
      concentrations in 2008 and C13* cells dropped to < 8% of basal levels within 30
      min after exposure to medium in which CI- had been replaced by NO3-. Lowering the
      intracellular CI- level should shift the equilibrium to the aquated form of the
      drug and thereby enhance cytotoxicity. Exposure of cells to DDP in equiosmolar
      CI(-)-deficient medium, however, did not change cytoxicity as measured by colony
      forming assay. Accumulation experiments at 1 hr confirmed that the same amount of
      platinum was entering the 2008 and C13* cells in normal or CI(-)-deficient media.
      Plantination of cellular DNA was also determined under normal and CI(-)-depleted
      conditions, but again no difference was found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736910
TI  - Fetal hepatic propranolol metabolism. Studies in the isolated perfused fetal
      sheep liver.
AB  - We have used an isolated perfused fetal sheep liver preparation to study the
      fetal hepatic metabolism of propranolol in vitro in the intact organ. Eight
      livers were perfused in situ via the umbilical vein in an oxygenated
      recirculating system at 300 ml/min. Radiolabeled 15-microns microspheres were
      used to quantify the hepatic ductus venosus shunt. Propranolol (4 mg) was dosed
      into the reservoir as a single bolus and perfusate and bile sampled over 150 min.
      Propranolol, 4-hydroxy propranolol (4OHP), 5-hydroxy propranolol (5OHP),
      desisopropylpropranolol (DIP), naphthoxylactic acid (NLA), and alpha
      naphthoxyacetic acid (NAA) were assayed by HPLC, before and after deconjugation
      by enzyme hydrolysis. Mean age was 125 +/- 10 days, and mean liver weight was
      66.1 +/- 18.8 g. Oxygen consumption (1.10 +/- 1.03 mumol/g/min), bile flow (0.51
      +/- 0.18 microliters/g/min), and perfusion pressure (8.7 +/- 3.3 mm Hg) were
      stable. Ductus venosus shunt was 41.6 +/- 17.4% of umbilical vein flow.
      Propranolol clearance was 26.2 +/- 13.4 ml/min, and shunt-corrected extraction of
      propranolol was 0.26 +/- 0.13. The relative amounts of metabolites in perfusate
      after 150 min were: 4OHP (25.1%), 5OHP (5.08%) (ring-oxidation products), DIP
      (6.57%), and NLA (4.33%) (side-chain oxidation products). No alpha NAA (a product
      of N-dealkylation of NLA) was detected. Except for NLA, metabolites were present
      predominantly as conjugates. Biliary excretion of unchanged drug and metabolites
      accounted for a further 1.33% of the propranolol dose. These data indicate that,
      although the hepatic clearance and extraction of propranolol are low, the fetal
      sheep liver can metabolize propranolol by both ring- and side-chain oxidation
      reactions and can conjugate these metabolites.

PMID- 7736909
TI  - Metabolism of L-689,502 by rat liver slices to potent HIV-1 protease inhibitors.
AB  - L-689,502, N-[2(R)-hydroxy-1(S)-indanyl]-5(S)-(1,1-dimethylethoxy- carbonyl
      amino)-4(S)-hydroxy-6-phenyl-2(R)-(4-[2(R)-(4-morpholinyl)
      ethoxy]phenyl)methylhexamide, is a potent and specific inhibitor of human
      immunodeficiency virus-type 1 (HIV-1) protease in vitro. Metabolism of this
      compound in rat liver slices produced four major and several minor metabolites.
      The major metabolites were identified as morpholin-2-one, 3'(S)-hydroxyindan and
      4'-hydroxyindan analogs, and a 4-O-glucuronic acid conjugate of the parent
      compound. The metabolites were characterized by Heteronuclear Multiple Quantum
      Coherence and Nuclear Overhauser Effect techniques in NMR spectroscopy, by MS,
      and/or comparison with authentic standards. Two of the minor metabolites were
      similarly characterized as a 2(R)-[4-(2-carboxymethoxy)phenyl]methyl analog and a
      product with a degraded morpholino ring. The hydroxyindan metabolites were lower
      in activity than L-689,502, whereas the morpholin-2-one and carboxymethoxyphenyl
      analogs were approximately 6- and 11-fold more potent as inhibitors of HIV-1
      protease, respectively.

PMID- 7736911
TI  - Disposition of ciprofloxacin in the isolated perfused rat liver.
AB  - Ciprofloxacin (CIP), a quinolone with a wide spectrum of antibacterial activity,
      was studied in the isolated perfused rat liver. Three concentrations (1, 5, and
      25 mg/liter) were used in the perfusion medium to check whether hepatic
      transformation and/or biliary elimination of this drug was dose-dependent.
      Pharmacokinetic parameters of CIP in the perfusion medium were similar when
      normalized for the dose at all three concentrations. Some dose-dependent changes
      were observed in biliary excretion of CIP. CIP biliary clearance and the
      percentage of excreted drug differed at 25 mg/liter and the lower concentrations.
      In addition, the chromatograms of the bile samples at the highest dose showed a
      peak that never appeared at the lower concentrations. This evidence, together
      with the zwitterion characteristics of CIP, reaching a bile/medium area under the
      concentration-time curve ratio > 10, suggests that an active transport mechanism
      is involved in the drug's biliary excretion, as has been demonstrated for its
      renal elimination.

PMID- 7736912
TI  - Inactivation of constitutive hepatic cytochromes P450 by phencyclidine in the
      rat.
AB  - The purpose of this study was to determine whether phencyclidine (PCP) inhibits
      constitutive hepatic cytochrome P450 (CYP) isozymes when administered to naive
      adult male Sprague-Dawley rats. Animals were pretreated with PCP (25 mg/kg/day
      for 2 days), killed 3 and 16 hr after the last dose, and liver microsomes
      prepared. The washed microsomes were then assayed for benzphetamine,
      methamphetamine (MA), and methylenedioxymethamphetamine (MDMA) N-demethylation
      together with MDMA demethylenation and MA 4-hydroxylation activities. MDMA
      demethylenation (low substrate concentration), MA 4-hydroxylation, and metoprolol
      alpha-hydroxylation reactions, which are catalyzed by CYP2D isozymes, were
      reduced > 74% 3 hr after the last PCP dose and were only partially restored 13 hr
      later. Benzphetamine and (-)-MDMA N-demethylation activities were restored to
      control values 16 hr after the last dose. These results indicate that PCP
      suppresses constitutive isozymes, including CYP2C11 and members of the CYP2D
      subfamily. The suppression of cytochromes P450 activity by PCP in vivo is
      consistent with its in vitro actions found in this and other studies, and
      demonstrates that alteration of CYP activity is another pharmacological effect of
      this compound.

PMID- 7736914
TI  - Gastrointestinal distribution of the prodrug loperamide oxide and its active drug
      loperamide in the dog.
AB  - Loperamide oxide is a prodrug of the effective antidiarrheal loperamide.
      Administration of this prodrug improves efficacy and tolerability. For better
      understanding of these effects, the absorption and gastrointestinal distribution
      of loperamide oxide and of its active drug loperamide were studied. Beagle dogs
      received a single oral dose of loperamide oxide or loperamide at 0.16 mg/kg.
      Plasma, gastrointestinal contents and tissues, and some other organs were
      obtained. Concentrations were determined by specific radioimmunoassays.
      Loperamide oxide was gradually converted to loperamide in the gastrointestinal
      tract. After administration of the prodrug, the systemic absorption of the active
      drug was lower and more delayed than after administration of loperamide itself.
      As a consequence, more loperamide was available in the contents and the mucosa of
      the gut, in particular in the lower part of the small intestine and in the large
      intestine. The higher levels of loperamide in mucosa may cause more pronounced
      and longer lasting antisecretory effects after administration of loperamide
      oxide. The results of this study are in line with the hypothesis that loperamide
      oxide is a site-specific prodrug that acts as a chemically designed controlled
      release form of loperamide keeping a higher amount of the active drug for a
      longer time at the site of action in the gut wall.

PMID- 7736913
TI  - Biotransformation of losartan to its active carboxylic acid metabolite in human
      liver microsomes. Role of cytochrome P4502C and 3A subfamily members.
AB  - Losartan is a 4-chloro-5-hydroxymethylimidazole derivative that is a potent and
      highly selective angiotensin II receptor antagonist. Losartan is metabolized in
      vivo in rats, monkeys, and humans to a carboxylic acid derivative E3174 that is
      pharmacologically more active than the parent compound. We have investigated the
      mechanism of this biotransformation in human liver preparations. The oxidation of
      both losartan and the putative aldehyde intermediate E3179 was catalyzed by the
      microsomal fraction, required both NADPH and molecular oxygen, and was inhibited
      by SKF 525-A, implicating cytochrome P450 (CYP). When incubations with each
      substrate were performed under an atmosphere of 18O2, the extent of 18O
      incorporation into the carboxylic acid product was consistent with a mechanism
      for losartan oxidation involving an aldehyde intermediate. To substantiate the
      involvement of CYP in these reactions, incubations with losartan and the aldehyde
      E3179 were performed in the presence of isoform-selective inhibitors. Inhibitors
      of CYP3A4/5 (gestodene and ketoconazole) and CYP2C9/10 (sulfaphenazole)
      attenuated the oxidation of both substrates. It was then demonstrated that
      microsomes containing either recombinant human liver CYP2C9 or CYP3A4 were
      capable of oxidizing both losartan and the aldehyde E3179 to the carboxylic acid
      E3174. Subsequently, it was shown that rabbit anti-CYP2C9 and anti-CYP3A3/4
      inhibited the oxidation of losartan to E3174 in incubations with human liver
      microsomes. These studies support the hypothesis that the aldehyde E3179 is an
      intermediate in the oxidation of losartan and that this two-step reaction is
      catalyzed in human liver microsomes by members of the CYP3A and CYP2C
      subfamilies.

PMID- 7736915
TI  - Pharmacokinetics and bioavailability of 5-ethyl-2'-deoxyuridine and its novel
      (5R,6R)-5-bromo-6-ethoxy-5,6-dihydro prodrugs in mice.
AB  - The pharmacokinetics and oral (po) bioavailability of 5-ethyl-2'-deoxyuridine
      (EDU) and its novel 5,6-dihydro prodrugs (+)-trans-(5R,6R)-5-bromo-5-ethyl-6
      ethoxy-5,6-dihydro-2'-deoxyuridine (BEEDU) and (+)-trans-(5R,6R)-5-bromo-5-ethyl
      6-ethoxy-5,6-dihydro-5'-O-valeryl-2'- deoxyuridine (VBEEDU) were determined in
      male Balb/C mice following intravenous and no administration of a 0.4 mmol/kg
      dose. EDU was eliminated from blood with a half-life of 35.2 +/- 4.2 min. The
      mean residence time (MRT) and the area under the blood vs. time curve (AUC) for
      EDU after iv injection were 45.1 +/- 11.7 min and 1.7 +/- 0.2 mumol.g-1.min,
      respectively. EDU showed a 49% bioavailability in male.Balb/C mice. The
      pharmacokinetic parameters and bioavailability of EDU were improved significantly
      upon administration of the 5,6-dihydro prodrugs BEEDU or VBEEDU. The AUC of EDU
      after a 0.4 mmol/kg iv dose of BEEDU was 2.1 +/- 0.3 mumol.g-1.min, which is
      substantially higher than that after iv injection of EDU. The half-life and MRT
      of EDU were increased to 251.9 +/- 30.2 min and 352.0 +/- 91.5 min, respectively,
      after injection of BEEDU. The po bioavailability of EDU, after administration of
      BEEDU, was increased almost 2-fold (81%), compared with that of EDU (49%). The
      AUC of EDU after iv injection of VBEEDU was 1.8 +/- 0.2 mumol.g-1.min. The half
      life and MRT of EDU, the active metabolite of VBEEDU, were 106.0 +/- 23.2 min and
      157.0 +/- 40.8 min, which are substantially higher than those for EDU after
      administration of EDU.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736916
TI  - Time- and dose-dependent kinetics of all-trans-retinoic acid in rats after oral
      or intravenous administration(s).
AB  - The kinetics of all-trans-retinoic (RA) acid are known to be nonlinear. To
      clarify the mechanisms involved, RA kinetics were determined in four groups of
      rats: group 1 received a single 2-mg RA dose intravenously (N = 5); group 2
      received the same treatment as group 1 after 12 days of oral RA (2 mg/day) (N =
      6); group 3 received a single, oral 2-mg (N = 6) or 5-mg RA dose (N = 6); and
      group 4 (N = 5 + 3) received the same treatment as group 3 after 12 days of oral
      RA (2 mg/day). Blood samples, 10-12/animal, were taken during the 7 hr following
      the final dosage. Plasma RA concentrations were determined by liquid
      chromatography. Noncompartmental analysis showed that RA disposition after
      intravenous bolus dosing obeyed Michaelis-Menten (MM) kinetics in group 1 (no
      pretreatment) and linear kinetics in group 2 (pretreated), with a lower area
      under the concentration vs. time curve, which suggested time-dependent kinetics
      with autoinduction. The same autoinduction phenomenon was observed after oral
      dosing in groups 3 and 4. Moreover, the mean area under the concentration vs.
      time curve was not higher after 5 mg dosing than after 2 mg dosing, which
      indicated a saturable mechanism of absorption. Fitting the data to a three
      compartment model with saturable absorption and elimination kinetics confirmed
      the autoinduction of RA elimination (maximal velocity of elimination = 3330 vs.
      541 micrograms/hr, p = 0.006, MM constant KMe = 7.53 vs. 1.10 micrograms/ml, p =
      0.006) after 12 days RA administration, and an MM absorption mechanism resulting
      in a saturable absorption (bioavailability F = 0.58 at 2 mg vs. 0.25 at 5 mg,
      group 3) that decreased after 12 days of RA treatment: the maximal velocity of
      absorption decreased from 1632 (group 3) to 631 micrograms/hr (group 4) (p =
      0.02). The volume of distribution also decreased after pretreatment, which
      indicated a modification in tissular distribution (565 vs. 358 ml, p < 0.001,
      group 3 vs. 4).

PMID- 7736917
TI  - Metabolism and elimination of oxazepam in F344 rats.
AB  - The antianxiety agent, oxazepam, is a mouse liver carcinogen as determined by a
      National Toxicology Program bioassay. An equivalent study in the F344 rat is
      currently in progress. In an effort to gain insight into whether the mouse or rat
      will be a better model for human risk assessment, extensive comparative
      metabolism studies have been conducted in both rodent species and compared with
      the human literature. In this study, male rats were treated with 25, 250, or 500
      mg/kg of radiolabeled oxazepam. In addition, sex comparisons were made at 500
      mg/kg after 0 and 14 days of 2500 ppm oxazepam in the feed to mimic bioassay
      conditions. Similar studies have already been conducted in mice. Recovery of
      administered activity was dose-dependent, with recovery approaching 100% at the
      low dose. In all groups, the order of importance of route of elimination was
      fecal > urinary > expired. No significant sex-dependent differences were
      detected. Oxidative metabolism and sulfate conjugation were the major routes of
      metabolism. Pretreatment of animals with oxazepam-dosed feed resulted in evidence
      of hepatic enzyme induction. The rate of elimination for all three routes of
      elimination was elevated by dosed feed treatment. With regard to metabolite
      profile and routes of elimination, the rat is less like a human than the mouse.

PMID- 7736918
TI  - Influence of severity of inflammation on the disposition kinetics of propranolol
      enantiomers in ketoprofen-treated and untreated adjuvant arthritis.
AB  - Clearance of the beta-blocker, propranolol (PR), is decreased in inflammatory
      conditions such as arthritis, in both humans and rats. However, inflammation in
      arthritic patients is often controlled by drugs such as the nonsteroidal
      antiinflammatory drugs (NSAIDs). Therefore, it is possible that arthritic-induced
      changes in drug disposition are minimized or suppressed in subjects receiving
      NSAIDs. To examine this hypothesis, we induced mild and severe adjuvant arthritis
      (AA) in rats and daily doses of the NSAID, ketoprofen (KT), were given to half of
      these rats. The pharmacokinetics of PR were thus examined in nontreated
      (MILDcontrol and SEVEREcontrol) and KT-treated (MILDKT and SEVEREKT) arthritic
      rats. Treatment with KT significantly reduced the arthritic index (AI) in the
      severe model of AA. In AA, the AUC0-8 of R- and S-PR were not significantly
      different in MILDKT rats (R, 15.8 +/- 9.5; S, 1.72 +/- 9.1 mg.hr/liter) as
      compared with MILDcontrol rats (R, 16.2 +/- 12; S, 1.76 +/- 1.2 mg.hr/liter). On
      the other hand, the AUC0-8 of both enantiomers were significantly lower in
      SEVEREKT (R, 39.2 +/- 13.2; S, 2.92 +/- 1.2 mg.hr/liter) as compared with
      SEVEREcontrol (R, 79.9 +/- 17; S, 6.88 +/- 2.1 mg.hr/liter). A high correlation
      between disease severity (AI) and the AUC0-8 of R- (r = 0.82) and S-PR (r = 0.81)
      was observed in all groups. Furthermore, the relationship between the AI and
      protein binding of R- and S-PR was significant in severe AA. Therefore, increased
      plasma concentrations of PR in arthritis are related to the degree of
      inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736919
TI  - Oxidation of 5-aminosalicylic acid by hypochlorous acid to a reactive
      iminoquinone. Possible role in the treatment of inflammatory bowel diseases.
AB  - 5-Aminosalicylic acid (5-ASA) is an agent widely used in the treatment of
      inflammatory bowel disease. 5-ASA has been shown to be a potential scavenger of
      the oxidants, such as hypochlorous acid (HOCl), that are released by neutrophils
      present in inflammatory bowel disease. We studied the oxidation of 5-ASA by HOCl
      and characterized the reaction pathway involving reactive intermediates. The
      reactive intermediates in the reaction of 5-ASA with HOCl were identified by use
      of a flow system interfaced with a Sciex API III mass spectrometer. The mass
      spectral analysis revealed the formation of iminoquinone and quinone reactive
      intermediates. The major stable product formed was identified as gentisic acid.
      The iminoquinone and quinone intermediates were trapped by glutathione (GSH) and
      the products analyzed by LC/MS. The major conjugate was formed from the quinone
      with one dominant isomer. In contrast, three isomers of the iminoquinone-GSH
      conjugates were observed in almost equal proportion. Covalent binding of the
      reactive intermediates to the alpha-chain of human hemoglobin was also observed.
      We propose that the iminoquinone is the major intermediate formed in the
      scavenging of neutrophil-generated HOCl by 5-ASA. Although this reaction may
      inactivate HOCl and be responsible for the antiinflammatory effects of the drug,
      it also forms reactive intermediates that covalently bind to protein and may be
      responsible for adverse reactions that are associated with the use of the drug.

PMID- 7736920
TI  - Role of aldehyde oxidase in the in vitro conversion of famciclovir to penciclovir
      in human liver.
AB  - Famciclovir is the diacetyl 6-deoxy derivative of the active antiviral
      penciclovir that is for use in the treatment of infections caused by the herpes
      family of viruses. The major pathway of conversion is via di-deacetylation to BRL
      42359, followed by oxidation to penciclovir. On oral dosing of famciclovir to
      humans, only penciclovir and BRL 42359 can be detected consistently in the
      plasma; thus, attention was focused on the oxidation reaction. This 6-oxidation
      occurred rapidly in human liver cytosol, had no requirement for cofactors, and
      followed simple Michaelis-Menten kinetics with a KM of 115 microM +/- 23 (N = 3).
      Using inhibitors of xanthine oxidase (allopurinol) and aldehyde oxidase
      (menadione and isovanillin), the relative roles of these enzymes in this process
      were determined. At a concentration of BRL 42359 that reflected plasma
      concentrations observed in humans (4 microM), both menadione (IC50 7 microM) and
      isovanillin (IC50 15 microM) caused extensive inhibition of the 6-oxidation
      reaction. In contrast, allopurinol caused no significant inhibition, confirming
      earlier in vivo work. At higher substrate concentrations (50 and 200 microM), the
      results with these inhibitors were broadly similar. These results provide strong
      evidence that aldehyde oxidase and not xanthine oxidase is responsible for the 6
      oxidation of BRL 42359 to penciclovir in human liver cytosol, and this is likely
      to reflect the in vivo situation.

PMID- 7736921
TI  - Benzoic acid glycine conjugation in the isolated perfused rat kidney.
AB  - The fate of varying input concentrations (0.002-372 microM) of benzoic acid was
      examined in the single-pass isolated perfused rat kidney preparation under
      constant flow rate (8 ml min-1.organ-1). With an increasing concentration of
      benzoate, the steady-state renal extraction ratio decreased from 0.24 to 0.1.
      Little unchanged drug was found in the urine; the urinary clearance of benzoate
      was low (0.018 ml-1 min-1.g-1) and concentration-independent, yielding a rather
      constant fractional excretion of approximately 0.2. Metabolic clearance, due
      primarily to conjugation with glycine to form hippuric acid, constituted the
      majority of total renal clearance, and this decreased with concentration. These
      divergent trends for the metabolic and urinary clearance with concentration
      suggest that benzoate net influx across the basolateral membrane has not been
      saturated. Upon fitting of the hippurate formation rates vs. the plasma unbound
      logarithmic average concentrations of benzoate, overall kinetic constants (KM =
      5.3 microM and Vmax = 195 nmol min-1.g-1) that likely reflect glycine conjugation
      were obtained. The formed hippurate either returned to the venous circulation or
      was excreted into urine without further biotransformation; the apparent renal
      extraction ratio (excretion rate/formation rate of hippurate) was quite high
      (approximately 0.48). Avid glycine conjugation and hippurate excretion thus
      occurred with administration of benzoic acid to the isolated perfused rat kidney.

PMID- 7736922
TI  - Oxidation of tolualdehydes to toluic acids catalyzed by cytochrome P450-dependent
      aldehyde oxygenase in the mouse liver.
AB  - Mouse hepatic microsomal enzymes catalyzed the oxidation of o-, m-, and p
      tolualdehydes, intermediate metabolites of xylene, to the corresponding toluic
      acids. Cofactor requirement for the catalytic activity indicates that the
      microsomes contain NAD- and NADPH-dependent enzymes for this reaction. GC/MS
      analyses of the carboxylic acids formed by incubation under oxygen-18 gas
      indicate that the mechanism for this oxidation is an oxygenation and a
      dehydrogenation for the NADPH- and NAD-dependent reaction. Vmax/Km (nmol/min/mg
      protein) ratios indicate that the NADPH-dependent activity is more pronounced
      than the NAD-dependent activity. These results suggest that the NADPH-dependent
      reaction is mainly responsible for the microsomal oxidation of tolualdehydes. The
      NADPH-dependent activity was significantly inhibited by SKF 525-A, disulfiram and
      menadione, inhibitors of cytochrome P450 (P450), suggesting the involvement of
      P450 in the reaction. In a reconstituted system, P450 MUT-2 (CYP2C29) purified
      from mouse hepatic microsomes catalyzed the oxidation of o-, m-, and p
      tolualdehydes to the carboxylic acids, and the specific activities (nmol/min/nmol
      P450) were 1.44, 2.81, and 2.32, respectively. Rabbit antibody raised against
      P450 MUT-2 significantly inhibited the NADPH-dependent oxidation of tolualdehydes
      to toluic acids by 88% (o-), 63% (m-), and 62% (p-) using mouse hepatic
      microsomes. The present study demonstrated that a mouse hepatic microsomal
      aldehyde oxygenase, P450 MUT-2, catalyzed the most of oxidative activity of
      tolualdehydes to toluic acids in the microsomes.

PMID- 7736923
TI  - Metabolites of L-735,524, a potent HIV-1 protease inhibitor, in human urine.
AB  - L-735,524, N-[2(R)-hydroxy-1(S)-indanyl]-5-(2(S)-(1,1-
      dimethylethylaminocarbonyl)-4-[(pyridin-3-yl)methyl]piperazin++ +-1-yl)-4(S)-
      hydroxy-2(R)-phenylmethylpentanamide, is a potent and specific inhibitor of the
      human immunodeficiency virus type 1 protease and is undergoing clinical
      evaluation. In an initial clinical study, noninfected male volunteers were
      administered single, 1000 mg oral doses of nonlabeled compound. Urine samples
      were collected over a period of 48 hr. Metabolic profile of the urine was
      determined by HPLC-UV comparison with that from a human liver slice incubation of
      radiolabeled L-735,524. Seven significant metabolites were isolated from pooled
      human urine, and were characterized by NMR, MS, and/or chromatographic
      comparisons with authentic standards. The major metabolic pathways were
      identified as: a) glucuronidation at the pyridine nitrogen to yield a quaternized
      ammonium conjugate, b) pyridine N-oxidation, c) para-hydroxylation of the
      phenylmethyl group, d) 3'-hydroxylation of the indan, and e) N
      depyridomethylation. A minor product was identified as 2',3'-trans-dihydroxyindan
      analog. Urinary excretion of L-735,524 and its metabolites represented a minor
      pathway of elimination. The intact parent compound seemed to be the major
      component in the urine, whereas the level of each metabolite was relatively low.

PMID- 7736924
TI  - Antipeptide antibodies targeted against specific regions of rat CYP2D1 and human
      CYP2D6.
AB  - Four peptides (pep23-33, pep26-38, pep283-297, and pep409-419) corresponding to
      unique sequences in rat cytochrome P450 (CYP) 2D1 and/or human CYP2D6 were
      selected for production of antipeptide antibodies. Rat liver microsomal protein
      was recognized by anti-serum to all four peptides in ELISAs; however, antisera
      against pep23-33 and pep26-36 proved not usable for any other applications.
      Western blots of microsomal protein from a cell line specifically expressing
      human CYP2D6 revealed that antisera to pep283-297 and pep409-419 recognized a
      single protein band of the same molecular size as CYP2D6. Antisera to pep283-297
      and pep409-419 recognized a rat microsomal protein presumed to be CYP2D1, because
      it comigrated with human CYP2D6 and had an apparent molecular size of 52 kDa. An
      unknown protein of approximately 85 kDa was also recognized by pep409-419.
      Recognition of microsomal protein(s) by antisera to pep283-297 and pep409-419 was
      blocked by pep283-297 or a bovine serum albumin-pep409-419 conjugate,
      respectively. Antiserum to pep283-297 was used to analyze sex and strain
      differences in liver microsomes prepared from Sprague-Dawley, Fischer 344, and
      Dark Agouti male and female rats. Sprague-Dawley and Fischer 344 rats expressed
      similar amounts of CYP2D1, but expression in Dark Agouti rats was significantly
      lower. The antiserum did not detect a sexual dimorphism in any of the strains. A
      significant correlation between antipeptide283-297 immunoreactivity and Vmax for
      dextromethorphan O-demethylation existed in female rat strains; however, this
      relationship did not exist in male rat strains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7736925
TI  - Contribution of the small intestine to the first-pass uptake and systemic
      clearance of propranolol in rabbits.
AB  - Epithelial cells of the intestine enclose isozymes able to metabolize
      propranolol, raising the possibility that the gut contributes with the liver to
      the first-pass uptake and systemic clearance of propranolol. To assess the role
      of the liver in the first-pass uptake, propranolol was injected into the jugular
      vein and a mesenteric vein of anesthetized New Zealand rabbits, and blood samples
      were drawn from the abdominal aorta, or it was injected into the intestine and
      samples were drawn simultaneously from the portal vein and the abdominal aorta.
      Extraction of propranolol by the liver was estimated to be 96-97%. To assess the
      intestinal extraction of oral propranolol, a porto-cava transposition was
      conducted in two groups of animals, and propranolol was injected into the first
      30 cm of the small intestine or into the jugular vein and samples were withdrawn
      from the abdominal aorta; propranolol extraction by the intestine was 43%. To
      document the contribution of the intestine in the systemic clearance of
      propranolol, propranolol was injected into the jugular vein and blood samples
      were drawn simultaneously from the abdominal aorta (before the gut) and from the
      portal vein (after the gut); propranolol extraction from the systemic circulation
      by the intestine was 24%. Only the liver generated detectable amounts of
      conjugated metabolites of propranolol. In the in vitro studies, it was shown that
      propranolol was rapidly metabolized by the liver, yielding 4-hydroxypropranolol
      and conjugates of propranolol; propranolol metabolism in the proximal small
      intestine was slower and yielded only 4-hydroxypropranolol.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7736926
TI  - Oxidation of the angiotensin II receptor antagonist losartan (DuP 753) in human
      liver microsomes. Role of cytochrome P4503A(4) in formation of the active
      metabolite EXP3174.
AB  - The oxidative metabolism of losartan (DuP 753), a novel angiotensin II receptor
      antagonist, by human liver microsomes and purified cytochrome P450 (P450)
      enzymes, was studied. The primary route of metabolism of losartan is by oxidation
      of the C5-hydroxymethyl to the carboxylic acid (EXP3174), which is an active
      metabolite of losartan. When microsomes prepared from different human liver
      samples were compared, EXP3174 formation activity was well correlated (r2 = 0.93)
      with nifedipine oxidation (a marker of P4503A4), but not with markers for other
      human liver P450s. Microsomal oxidation of losartan to EXP3174 was markedly
      inhibited by gestodene and ketoconazole, selective inhibitors of P4503A enzymes,
      but not by any of several other P450 inhibitors. Antibodies raised against
      P4503A4 could inhibit most of the oxidation of losartan to EXP3174 in a
      microsomal sample having high catalytic activity, but antibodies recognizing
      other P450s had no effect. The oxidation of losartan to EXP3174 was catalyzed by
      purified human liver microsomal P4503A4 and by purified bacterial recombinant
      P4503A4. These results provide evidence that P4503A4 (and possibly other P4503A
      enzymes) play a major role in the formation of an active metabolite EXP3174.

PMID- 7736927
TI  - Contribution of oxidation and deacetylation to the bioactivation of acetaminophen
      in vitro in liver and kidney from male and female Sprague-Dawley rats.
AB  - Young adult female Sprague-Dawley (SD) rats are more susceptible to acetaminophen
      (APAP)-induced nephrotoxicity than are age-matched male SD rats. Mechanisms
      contributing to sex-dependent APAP nephrotoxicity may involve differences in APAP
      bioactivation via cytochrome P450-dependent metabolism to N-acetyl-p
      benzoquinoneimine and/or deacetylation to para-amino-phenol. APAP bioactivation
      by oxidation and deacetylation was assessed by examining the effects of 1
      aminobenzotriazole (ABT), a suicide substrate inhibitor of cytochrome P450, and
      bis-(para-nitrophenyl) phosphate (BNPP), a reversible carboxyesterase inhibitor,
      on covalent binding of APAP-derived radiolabel. Hepatic and renal S9 fractions
      prepared from naive male and female rats were incubated with [14C-ring]-APAP in
      the presence and absence of NADPH. There were no sex-related differences in
      covalent binding of APAP-derived radiolabel in hepatic or renal S9 fractions from
      male and female rats. In both sexes, incubation of hepatic or renal S9 fractions
      with 10 mM ABT significantly reduced covalent binding of APAP-derived radiolabel
      as compared with covalent binding in the absence of ABT. In contrast, incubation
      of renal and hepatic S9 fractions with 10 mM BNPP did not alter covalent binding
      of radiolabel derived from APAP in either males or females. Thus, at least in
      vitro, differences in bioactivation of APAP in liver and kidney from male and
      female SD rats do not seem to contribute to sex-dependent APAP toxicity.
      Carboxyesterases inhibited by BNPP do not seem to contribute to covalent binding
      of APAP-derived radiolabel in vitro in either liver or kidney.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7736928
TI  - Comparison of acetyl coenzyme A:arylamine N-acetyltransferase activity in the
      liver, kidney, and intestine of male and female rats from three strains.

PMID- 7736929
TI  - [Sinusitis in HIV infection].
AB  - Case notes of 722 HIV-infected patients who had died between March 1986 and
      August 1993 were analysed to evaluate the prevention and characteristic features
      of sinusitis associated with HIV infection. In 73 patients (10%) sinusitis had
      been diagnosed at least once on the basis of radiological or clear-cut clinical
      criteria. In addition, 15 patients with sinusitis were identified among those
      attending an HIV out-patient clinic. There were altogether 126 episodes of
      sinusitis in 88 patients (62 men, 26 women; mean age 33 [19-69] years). In 62
      patients the CD4 lymphocyte count was under 100/microliters. The most commonly
      affected site was the maxillary sinuses. Patients with mirror formation had a
      significantly longer duration of illness than those without (P = 0.021). In 58
      patients the symptoms of fever, headache and rhinitis were predominantly caused
      by the sinusitis, in 49 only partially so, and in 19 sinusitis was a chance
      diagnosis. In 10 of 49 attacks of sinusitis the concurrent disease (e.g. cerebral
      toxoplasmosis, malignant non-Hodgkin lymphoma) had not been recognized by the
      referring doctor. There were 1-5 recurrences over an observation period of 11.8
      (0-72) months in 23 patients.-These findings show that sinusitis frequently
      occurs in HIV-infected patients, takes a protracted course and is difficult to
      distinguish from concomitant diseases by its clinical presentation. If symptoms
      persist, possible concurrent respiratory infection or CNS involvement must be
      looked for. Sinus needle aspiration is of decisive importance to ascertain the
      causative organism.

PMID- 7736930
TI  - [The recanalization of chronic coronary artery occlusions: what factors influence
      success?].
AB  - Between January 1986 and June 1990, recanalization with guide-wire and balloon
      angioplasty (PTCA) was attempted in 509 patients (416 men, 93 women; mean age
      57.5 +/- 9 years) with chronic coronary artery occlusions. The data recorded were
      analysed to determine the factors which influenced the outcome. The intervention
      was initially successful in 284 patients (55.8%; circumflex branch: 50%; right
      coronary artery: 52%; venous bypass graft: 50%; anterior interventricular branch:
      64%). The success rate was markedly reduced if (1) the occlusion had persisted
      for more than 6 months (9.5%; P < 0.001); (2) occlusion had occurred at or after
      a vessel kink (28.5%; P < 0.001); (3) there had been no vessel "stump" (36%; P <
      0.01) and (4) the occlusion was longer than 10 mm (40.7%; P < 0.05). The success
      rate was higher if (1) intracoronary anastomoses were absent (61.2%); (2)
      occlusion had occurred in a straight vessel (62.6%); (3) there had been a vessel
      stump (64%); (4) the occlusion had persisted for less than 4 weeks (68.5%) and
      (5) the length of occlusion was < or = 10 mm (75.8%).-These data indicate that
      the success of PTCA after chronic coronary artery occlusion depended on the site
      of occlusion, its duration and length, absence of orthograde collaterals and the
      presence of a vessel stump. Knowing the extent of these factors helps in
      delineating the indications.

PMID- 7736931
TI  - [Syringomyelia as a rare cause of respiratory insufficiency requiring
      ventilation].
AB  - For 17 years a now 45-year-old man had suffered from progressively more severe
      flaccid paresis of the arms and thoracic muscles, spastic paralysis of the legs
      and kyphoscoliosis. Artificial ventilation was required when he contracted
      pneumonia. Although it was being treated with antibiotics, frequent
      bronchoalveolar lavage had to be done because of repeated atelectases. After 6
      weeks clonuses developed in the legs, predominantly on the right, stretch
      synergisms and opisthotonos. The pupils were small with sluggish reaction to
      light, and there was a positive "doll's head" phenomenon. The level of
      consciousness alternated between somnolence and sleepiness. Magnetic resonance
      imaging demonstrated cavities in cervical and thoracic spinal cord, supporting
      the diagnosis of an abnormal cerebrospinal circulation due to gliosis in
      syringomyelia. To secure cerebrospinal fluid drainage, the cerebellar tonsils
      were resected, together with a duraplasty and partial resection of the atlas.
      Following this he became fully conscious and the spastic state improved. During
      the following 8 weeks it became possible gradually to wean him from the
      artificial ventilation and achieve satisfactory mobilization so that he could be
      discharged to domiciliary care.

PMID- 7736932
TI  - [Calcitriol administration during pregnancy in a partial DiGeorge anomaly].
AB  - A 23-year-old pregnant woman was known since birth to have partial DiGeorge
      syndrome with idiopathic hypoparathyroidism and clinically suspected thymus
      hypoplasia. The hypocalcaemia had until recently been treated with 1000 IU
      vitamin D3 daily. During the 9th week of pregnancy the serum calcium level was
      1.9 mmol/l, the phosphate one 1.58 mmol/l and parathormone 5.6 pg/ml. To ensure
      better control, calcitriol was given (1.25-[OH]2-vitamin D3, initially 1
      microgram daily and then, from the 22nd week of pregnancy onward, 1.5 micrograms
      daily), as well as calcium gluconate and lactate (initially 300 mg daily, then
      900 mg daily). The serum calcium level at that time was between 2.0 and 2.5
      mmol/l. Because of toxaemia of pregnancy the patient was hospitalized and
      confined to bed during the 37th week, whereupon the serum calcium level rose from
      2.2 to 2.7 mmol/l, but a decrease in calcitriol dosage resulted in a decrease to
      within normal limits within one day. A girl was delivered by section in the 39th
      week: she had normal serum calcium and phosphate levels and appeared healthy.

PMID- 7736933
TI  - [Sicca symptoms during systemic therapy with beta-receptor blockers].

PMID- 7736934
TI  - [Acute myocardial ischemia, ventricular tachyarrhythmias and sudden cardiac
      death].

PMID- 7736935
TI  - [The Nobel Prize for Medicine 1994].

PMID- 7736936
TI  - [Legal problems in research in emergency and intensive-care medicine].

PMID- 7736937
TI  - [Hepatitis A inoculation].

PMID- 7736938
TI  - [Magnesium infusion in acute myocardial infarct].

PMID- 7736939
TI  - [The recanalization of long-range femoral artery occlusions].

PMID- 7736940
TI  - [Encephalopathy following poisoning with an anticholinergic agent].

PMID- 7736941
TI  - [GISSI III: the effect of lisinopril and the transdermal application of
      nitroglycerin after an acute infarct. Gruppo Italiano per lo Studio della
      Streptochinasi nell'Infarto Miocardico].

PMID- 7736942
TI  - [HIV transmission in heterosexual partners].

PMID- 7736943
TI  - ["... One egg like the other?" The genetic variability of monozygotic twins and
      its possible effect on concordance studies in immunological diseases].

PMID- 7736944
TI  - [The fine-needle aspiration cytology of lymph nodes suspected of malignancy. Its
      diagnostic value and capacity to predict the histogenesis].
AB  - To examine the usefulness of fine needle aspiration cytology in the investigation
      of patients with enlarged lymph nodes, the authors made a retrospective
      evaluation of the results of 1158 aspirations in 838 patients (630 male, 208
      female, mean age 44 [4-90] years). In these 1158 cases the diagnosis was verified
      histologically, serologically or by follow up extending over at least six months.
      In 94.6% (n = 1096) the aspirate gave an unequivocal diagnosis, in 4.2% (n = 48)
      the diagnosis was equivocal and in 1.2% (n = 14) no diagnosis was reached. There
      were 773 correct malignant results, 368 correct benign results and 16 false
      benign; in one case the assessment was false malignant. Sensitivity was 98% and
      specificity 99.7%. In benign lymphadenopathies the investigation achieved a
      specificity of 99.7%, and in metastases and malignant lymphomas the sensitivity
      was 97.8% and 98.2% respectively. In 211 out of 286 aspirations the cytological
      diagnosis correctly predicted the subsequent histological diagnosis; in 58 cases
      correct though imprecise expressions such as "highly malignant non-Hodgkin's
      lymphoma" were employed. No serious complications were encountered. Fine needle
      aspiration cytology enables the clinician to devise an exact diagnostic and
      therapeutic plan in nearly every patient with unexplained lymph node enlargement.

PMID- 7736945
TI  - [Liver transplantation in familial amyloidosis].
AB  - A 32-year-old Portuguese with hereditary amyloidosis had been suffering from
      polyneuropathy for 9 years. It began insidiously with polyneuropathic complaints
      in the legs which gradually got worse over the years and progressively impaired
      walking. He also had signs of autonomic neuropathy with severe orthostatic
      dysregulation, abnormal micturition and impotence. His general state had
      deteriorated during the last 3 years with a weight loss of 18 kg, due to
      treatment-resistant diarrhoea. As there is so far no known cure of the
      amyloidosis, which usually ends fatally from cachexia after an average of 10
      years, liver transplantation was performed to reduce amyloid production and thus
      favourably influence the course of the disease. The patient's general condition
      has remained stable 32 months after the transplantation.

PMID- 7736946
TI  - [Iatrogenic esophageal perforation in inoperable esophageal carcinoma. Its
      therapy with a plastic-coated metal stent].
AB  - A 60-year-old man was admitted to hospital because of severely impaired
      swallowing, retrosternal pain and marked weight loss. History and physical
      examination of the patient, whose general condition was obviously much reduced,
      pointed to carcinoma of the oesophagus. Contrast-medium swallow demonstrated
      subtotal stenosis in the oesophagus. Computed tomography and magnetic resonance
      imaging showed a space-occupying mass originating from the oesophagus, in close
      relationship to the trachea, main bronchi and descending aorta. Biopsy confirmed
      the diagnosis of oesophagus carcinoma and exploratory thoracotomy excluded
      curative surgical treatment. An attempt was made to introduce a feeding tube
      endoscopically to provide nutritional palliation. But the oesophagus was
      perforated during this manoeuvre and resulted in an oesophagobronchial fistula
      with subsequent mediastinitis and mediastinal emphysema. Using a self-expandable
      plastic-covered metal stent it was possible to cover the perforation and overcome
      the patient's dysphagia. The mediastinitis healed under intravenous
      administration of cefotaxim (2 g three times daily), netilmicin (400 mg daily)
      and metronidazole (500 mg three times daily), for 5 days.

PMID- 7736947
TI  - [Neopterin as an immunodiagnostic parameter].

PMID- 7736948
TI  - [Bone and its diseases. II. The dialog between osteoblasts and osteoclasts].

PMID- 7736949
TI  - [Stress ulcer prophylaxis 1995. Balancing between gastrointestinal bleeding and
      nosocomial pneumonia].

PMID- 7736950
TI  - [Physician and collector in the service of the Enlightenment. On the 300th
      anniversary of the birth of Christoph Jacob Trew (1695-1769)].

PMID- 7736951
TI  - [The clinical chemical demonstration of chronic alcoholism].

PMID- 7736952
TI  - [Combined kidney and pancreas transplantation in the late-stage diabetic
      syndrome].

PMID- 7736953
TI  - [Percutaneous alcohol instillation in functional thyroid autonomy].

PMID- 7736954
TI  - [The diagnosis of ascites].

PMID- 7736955
TI  - [The efficacy of the malarial vaccine SPf66].

PMID- 7736956
TI  - [Do steroid-eluting pacemaker electrodes permit programming at lower pacemaker
      pulse amplitudes?].
AB  - A study was undertaken on 107 patients (68 men, 39 women; mean age 68 [29-100]
      years) with steroid-eluting ventricular electrodes to determine whether in
      general these electrodes make it possible routinely to set pacemaker impulses at
      2.5 V instead of 5.0 V with an impulse duration of 0.5 ms. 3-12 months after
      implantation, impulse duration thresholds were 0.27 +/- 0.20 ms at 0.8 V, 0.13 +/
      0.09 ms at 1.6 V and 0.08 +/- 0.05 ms at 2.5 V impulse amplitude. Thus,
      employing a 100% margin of safety, it was possible to set the pacemakers of 103
      among the 107 patients at 2.5 V and 0.5 ms. In four patients it was not possible
      to achieve the 2.5 V and 0.5 ms setting. With one exception (stimulation
      threshold rose immediately after a current accident) no circumstances arose under
      which thresholds increased. These results demonstrate that, using steroid-eluting
      electrodes, ventricles can be reliably stimulated with 2.5 V and 0.5 ms in 96% of
      patients. However, since it is not possible in all patients, optimal stimulation
      parameters must be determined in each patient even when steroid-eluting
      electrodes have been implanted.

PMID- 7736957
TI  - [High-grade coronary stenosis due to a bronchogenic cyst].
AB  - A 32-year-old woman without preceding illness or significant cardiovascular risk
      factors was admitted to hospital because of a syncope after physical exertion.
      Transoesophageal echocardiography, performed to exclude aortic dissection, showed
      as an incidental finding a cystic space-occupying mass, 5 x 6 cm in diameter,
      dorsal to the aortic root and main pulmonary artery. Exercise ECG had S-T segment
      depressions of about 0.3 mV, associated with anginal symptoms, so that inadequate
      coronary artery flow on exertion was suspected. Subsequent coronary angiography
      demonstrated a funnel-shaped 80% stenosis at the origin of the main left coronary
      artery, while all other coronary arteries were normal and smooth-walled. A causal
      connection between the two findings was assumed and quickly undertaken surgical
      intervention revealed an intrapericardial bronchogenic cyst which, presumably as
      a result of its size and location, had pressed on the main stem of the left
      coronary artery and caused the stenosis of its ostium. The cyst was completely
      resected and angioplasty of the coronary artery ostium was performed to ensure
      its patency. 3 months postoperatively the patient underwent an exercise test of
      up to 125 Watt without signs of ischaemia. This case presents a previously
      unreported complication of a bronchogenic cyst.

PMID- 7736958
TI  - [Severe pneumonitis as a complication of low-dose methotrexate therapy in
      psoriasis-associated polyarthritis].
AB  - A 71-year-old woman with psoriasis-associated rheumatoid arthritis had for 15
      months been treated with methotrexate (5 mg/week orally). Four weeks before
      admission she had developed dyspnoea and cough. On admission her axillary
      temperature was 38.2 degrees C, the white cell count was normal. Erythrocyte
      sedimentation rate (50/90 mm), lactate dehydrogenase activity (449 U/l) and the
      creatinine level (1.33 mg/dl) were all elevated. Blood gas analysis revealed
      partial respiratory impairment (pO2 52 mm Hg), and the chest X-ray demonstrated
      bilateral interstitial-alveolar changes. Despite antibiotics the temperature
      continued to rise, and on the 11th day a blood eosinophilia of 4% was noted. The
      bronchial mucosa was normal on bronchoscopy, and transbronchial biopsy showed
      only minor interstitial fibrosis, occasional macrophages and lymphocytes.
      Cultures of the lavage-fluid were negative. As methotrexate pneumonitis was
      suspected the drug was discontinued and prednisolone administered (50 mg daily
      for 3 days, gradually reducing over 7 days). The symptoms quickly improved, and
      blood gas analysis and the X-rays became normal. The patient was discharged
      symptom-free after 30 days.

PMID- 7736959
TI  - [Intraoperative anaphylaxis due to natural latex in a 3-year-old boy].
AB  - A nearly three-year-old boy with a genitourinary malformation, which had already
      been operated on several times, developed generalized urticaria, facial swelling
      and bronchospasm within 15 minutes of the induction of anaesthesia. The signs
      quickly responded to the administration of methylprednisolone (32 mg), clemastine
      (10 mg) and ranitidine (25 mg). There was a twofold positive immediate reaction
      in the prick test to natural rubber latex (white and brown), and specific IgE was
      demonstrated against the latex (2.58 kU/l). On the other hand, prick tests with
      perioperatively administered drugs and an oral provocation test with an
      antibiotic administered in the perioperative period were negative. The history of
      itching caused by an indwelling bladder catheter, vesicles on the lips after
      sucking on a rubber dummy and the described findings on examination both point to
      the natural rubber latex as the responsible allergen. No complications occurred
      three months later during a surgical intervention under administration of
      steroids and H1- and H2-receptor antagonists, as well as avoidance of materials
      made of natural rubber latex.

PMID- 7736960
TI  - [Multiple endocrine neoplasia type 2a. Genetic screening in the familial tumor
      syndrome].

PMID- 7736961
TI  - [Non-Hodgkin's lymphoma of the tonsils following asbestos dust exposure].

PMID- 7736962
TI  - [Immunohistochemical staging as a quick-section method in radical
      lymphadenectomy].

PMID- 7736963
TI  - [Rational substitution with stored blood and blood components].

PMID- 7736964
TI  - [The direct estimation of cancer mortality from low-dose ionizing radiation: an
      international study].

PMID- 7736965
TI  - [Occupational health services].

PMID- 7736966
TI  - [From preventing hazards to maintaining working capacity].

PMID- 7736967
TI  - [The health of workers and unifying Europe].

PMID- 7736968
TI  - [Responsibility of the occupational physician in environmental protection].

PMID- 7736969
TI  - [Goal-directed occupational health services].

PMID- 7736972
TI  - [Occupational health services as support to entrepreneurship].

PMID- 7736971
TI  - [Periodic physical examination by occupational health services--does health
      improve with check-ups?].

PMID- 7736970
TI  - [Unemployment and everyday occupational health services].

PMID- 7736973
TI  - [Robberies of financial institutions].

PMID- 7736974
TI  - [As a worker in a foreign country].

PMID- 7736975
TI  - [Unemployment and risk of unemployment: crisis of an individual and of society].

PMID- 7736976
TI  - [Population responsibility and occupational health services].

PMID- 7736977
TI  - [With whom do you stand?].

PMID- 7736979
TI  - [Intensified treatment of diabetes prevents complications].

PMID- 7736978
TI  - [New parathyroid hormone which increases blood pressure?].

PMID- 7736980
TI  - [Antithrombotic treatment in chronic nonrheumatic atrial fibrillation].

PMID- 7736981
TI  - [Cartilage-hair hypoplasia--a Finnish growth disorder].

PMID- 7736982
TI  - [Protection when facing death].

PMID- 7736983
TI  - [In-situ hybridization in the diagnosis of, and carbon dioxide laser treatment of
      penile HPV infections].

PMID- 7736984
TI  - [Angioscopy--future method in diagnosis and treatment of cardiovascular
      diseases].

PMID- 7736985
TI  - [Luteoma--virilization-associated ovarian tumor of pregnancy].

PMID- 7736986
TI  - [Self-induced purpura as a diagnostic problem].

PMID- 7736987
TI  - [McArdle's disease].

PMID- 7736988
TI  - [George Washington Crile 1864-1943].

PMID- 7736989
TI  - [Diagnosis and treatment of urinary incontinence in women].

PMID- 7736990
TI  - [Treatment of prostatic cancer. The Finnish Academy and Duodecim].

PMID- 7736992
TI  - [Paradoxal embolism].

PMID- 7736991
TI  - [Greater focus on teaching].

PMID- 7736993
TI  - [Clinical use of albumin infusions].

PMID- 7736994
TI  - [Brain tumor and multiple sclerosis].

PMID- 7736995
TI  - [Does antihypertensive drug therapy have to be continued the rest of one's
      life?].

PMID- 7736996
TI  - [Clinical trials and new regulations].

PMID- 7736997
TI  - [Thrombolytic therapy in myocardial infarction].

PMID- 7736998
TI  - [New heparins--does it change prevention and treatment of venous thrombosis?].

PMID- 7736999
TI  - [Changing drug therapy of Parkinson disease].

PMID- 7737000
TI  - [Drug therapy of heart failure].

PMID- 7737001
TI  - [When and how should osteoporosis be treated?].

PMID- 7737002
TI  - [Should the use of anti-inflammatory analgesic drugs be estimated again?].

PMID- 7737003
TI  - [A difficult choice of ACE inhibitors].

PMID- 7737004
TI  - [Do the newer calcium channel blockers replace the older ones?].

PMID- 7737005
TI  - [A drug can have 2 faces].

PMID- 7737008
TI  - [New serotonin-receptor drugs for migraine and nausea].

PMID- 7737007
TI  - [Can endothelium be treated with drugs?].

PMID- 7737006
TI  - [Current hazardous drug interactions].

PMID- 7737009
TI  - [Transdermal administration of drugs--are there enough places for patches?].

PMID- 7737010
TI  - Mechanical muscle fibre conduction velocity of the biceps as measured by a new
      seismic technique.
AB  - A recently-developed technique, called seismic myography (SMG) has the
      characteristic of recording fast micro-mechanical response times. These times can
      be determined with sub-millisecond accuracy. The response times can be compared
      to response times of EMG recordings. The "muscular electro-seismic response"
      (MESR) latencies, due to direct electrical stimulation of the biceps muscle, are
      used for explorative measurements of the mechanical conduction velocity of the
      muscle fibres. The measurements are performed by means of a general-purpose
      physiological multimeter which is equiped with the micro-seismic function.
      Measurements are performed on two healthy subjects, aged 22 years. The MESR
      latencies are measured along a medial and a lateral trajectory on their biceps
      muscles. The MESR-latencies at stimulus-cathodal to seismic transducer distances
      of 2,0-3,5 cm, are in the range of 2.0-3.8 ms, while at distances in the range of
      7.5-8.9 cm the MESR-latencies varied between 3.4 and 4.7 ms. The calculated
      mechanical muscle fibre conduction velocities (MMFCV) are in the range between 36
      and 89 m/s. There is a reproducability error of maximum 20%. The MMFCV's of the
      lateral and medial trajectory do not differ within the accuracy of the present
      method. However, the MMFCV's are considerably higher than the electrical muscle
      fibre conduction velocities of MUAPS ((E)MFCV). Some aspects of the MMFCV and
      possible consequences to surface EMG recordings are discussed. It is concluded
      that this seismic method for measuring MMFCV is a new accessible and simple to
      handle tool for the description of muscle function, and offers an interesting new
      contribution in experimental muscular research.

PMID- 7737011
TI  - A comparison of motor evoked potentials and somatosensory evoked potentials in
      patients with multiple sclerosis and potentially related conditions.
AB  - Central motor conduction (CMC) and central sensory conduction (CSC) studied by
      means of magnetic cortical stimulation and recording of somatosensory evoked
      potentials, were examined and compared in 87 patients with multiple sclerosis or
      potentially related conditions. In all groups of patients (either grouped by
      diagnosis, clinical symptomatology or disease duration) there were more
      aberrations in CMC compared to CSC. This difference became statistically
      significant when all patients were taken together. By both methods we were able
      to detect signs of clinically silent lesions and these were often restricted to
      either of the pathways.

PMID- 7737012
TI  - Quadriceps mediated changes in soleus motoneuron excitability.
AB  - In an effort to investigate the interactions of the quadriceps and soleus
      muscles, the isometric force-time curve of the Achilles tendon-tap reflex (ATR)
      was measured in 10 college age subjects. The tendon-jerk was conditioned with a
      tap to the ipsilateral or contralateral patellar tendon, or by an
      electrocutaneous (3x perception) stimulus applied to the belly of the quadriceps.
      The conditioning stimulus preceded the test ATR by 25, 40, 55, 70, 85, 100, 115,
      130 or 145 ms. The results indicated that the ipsilateral conditioning tendon-tap
      produced a wave of short-latency facilitation (40 ms) and long-latency inhibition
      (85-130 ms) to the triceps surae muscles. The ipsilateral cutaneous conditioning,
      however, did not alter reflex excitability. A contralateral conditioning to the
      patellar tendon again produced short-latency (50-70 ms) facilitation, whereas the
      electrocutaneous stimulus did not alter motoneuron excitability. Moreover, a
      barrage of electrocutaneous impulses to either the ipsilateral or contralateral
      quadriceps (1 minute/60 pps) did not significantly alter motoneuron excitability
      of the soleus muscle. These results indicate that motoneuron excitability changes
      are observed in the soleus muscle with mechanical conditioning but not with
      electrocutaneous conditioning. Several neurophysiological mechanisms are proposed
      to mediate these changes.

PMID- 7737013
TI  - Multimodal evoked potentials and electroretinography in limb girdle muscular
      dystrophy.
AB  - Evoked potentials (EP) were recorded as part of a complete systems evaluation in
      20 strictly selected patients with limb girdle muscular dystrophy. Various
      abnormalities were detected in 68% (13/19) of patients: 21% (4/19) had visual EP
      abnormalities; 11% (2/19) had brainstem auditory EP abnormalities; 29% (5/17) and
      31% (5/16) had somatosensory EP abnormalities of the median and posterior tibial
      nerves, respectively. An electroretinogram abnormality was detected in 12% (2/17)
      of patients. There was no consistent correlation between the number, type or
      severity of EP abnormality and the age, sex, disease duration or degree of muscle
      weakness. The significance and etiology of these EP abnormalities need to be
      established by pathologic studies.

PMID- 7737014
TI  - Small fibre involvement in neuropathy associated with IgG, IgA and IgM monoclonal
      gammopathy.
AB  - A delta and C fibre function has been investigated in 18 patients affected by
      neuropathies associated with monoclonal gammopathies. Warm, cold and heat pain
      thresholds have been determined by means of a Somedic Thermotest, operating on
      the Peltier principle, in a room at constant temperature. Our results indicate
      that: 1) there is an involvement of A delta and C fibres in these neuropathies
      that might be difficult to quantitate only on clinical grounds 2) in IgG and IgA
      patients, all affected by a subclinical or mild axonal neuropathy, small fibres
      of both types are always involved 3) in IgM anti-MAG positive severe cases, A
      delta fibre involvement, suggestive of demyelination is evident, while in one
      anti-MAG negative patient only C fibres are damaged, probably reflecting a
      different pathogenetic mechanism.

PMID- 7737015
TI  - Neuromuscular dysfunction after surgical treatment of oral cancer.
AB  - Surgical treatment of oral cancer usually includes radical dissection of the
      neck, in which the sternocleidomastoid muscle is sacrificed. In modified neck
      dissection the accessory nerve is spared, but may be severed by e.g.
      manipulation. The facial nerve may also be severed by traction or distension. We
      have done an electromyographic study of 35 patients, 20 men and 15 women, aged
      from 21 to 92 yrs, 6 to 176 months after oral cancer operation. EMG findings of
      the upper trapezius muscle were normal in only six of 32 patients who had had a
      radical or upper neck dissection, although the accessory nerve had been
      identified and spared during surgery. The surgeons' evaluation of the risk to the
      facial nerve was in good correlation to EMG findings, both the orbicularis oris
      and the mentalis muscle were better preserved, if the risk was considered minor.
      The loss of motor units in voluntary contraction and the nerve latencies to the
      muscles were in good correlation to many factors from the spectral analysis of
      the EMG, e.g. to the root mean square (RMS), to the mean rectified value (MRV),
      to the mean amplitude and to the number of turns. The accessory nerve is easily
      damaged, and the injury is often not noted during neck dissection. Significant
      problems may also arise with lesions of the facial nerve. Quantitative EMG
      analysis may add to sensitivity of the postoperative EMG studies.

PMID- 7737016
TI  - Cortical somatosensory evoked potentials from lumbosacral dermatomes: airpuff
      versus electrical stimulation.
AB  - Cortical potentials were elicited by airpuff stimulation of the L5 and S1
      dermatome in a group of 24 healthy volunteers. The results were compared with the
      SEPs obtained by conventional electrical stimulation. Both stimulus modalities
      produce stable and good reproducible cortical responses of similar waveform. The
      most stable second negative peak, labeled N2, was used in this study. Mean
      latencies (in msec) were: N2 L5 air = 67.1 +/- 3.3, N2 L5 electr. = 55.7 +/- 3.7
      N2 S1 air = 67.2 +/- 3.9, and N2 S1 electr. = 55.1 +/- 2.9 The maximum R/L
      difference (mean + 3 SD) was 5.7 msec, 5.9 msec, 7.2 msec and 7.2 msec for
      respectively N2 L5 air, N2 L5 electrical, N2 S1 air and N2 S1 electrical. Single
      regression analysis showed a significant influence of height, but not age upon
      all latencies. Multiple regression analysis with height and age as independent
      variables showed a significant influence of height and age together upon the
      latencies of the electrical SEP (both L5 and S1). For the airpuff SEP only height
      was significant. Gender had no effect on the cortical components. The amplitude
      of peak N2 after electrical stimulation of the S1 dermatome was significant
      higher than after airpuff stimulation, 2.9 and 1.7 microvolt respectively. For
      the L5 dermatome both types of stimuli produced responses of nearly equal
      amplitude, 2.5 and 2.1 microvolt for electrical and airpuff stimulation
      respectively. Airpuff SEPs may provide a good alternative for electrical
      stimulation.

PMID- 7737017
TI  - Experimentally induced beriberi polyneuropathy in chickens.
AB  - Chickens fed with the same composition of diet as our low income beriberi
      polyneuropathic patients, developed clinical symptoms of thiamine deficiency in
      22.3 +/- 6.3 days. There appeared to be a body store of thiamine which is
      utilized during a period of deficient intake. Haemoglobin content and serum
      albumin did not change appreciably during thiamine deficiency. The blood thiamine
      content was low and the thiamine pyrophosphate (TPP) effect increased to more
      than 25 percent during the development of the beriberi polyneuropathy, which
      resumed after one week on thiamine tetrahydrofurfuryl disulfide (TTFD) treatment.
      However, the clinical features gradually improved after about one month.
      Neurophysiological findings including somatosensory evoked potentials (SSEPs) and
      neuromorphological studies of the peroneal and sciatic nerves were compatible
      with a major degree of axonal degeneration and secondary minimal segmental
      demyelination. We may conclude that the experimentally induced beriberi
      polyneuropathy in chickens seems a good model for studying these forms of
      neuropathy in view of diagnosis and treatment.

PMID- 7737018
TI  - Motor fibers in human sural nerve.
AB  - Two cases of anomalous innervation of the abductor digiti quinti muscle of the
      foot via sural nerve are described. This anatomical variation can be discovered
      only when antidromic sensory conduction is investigated. The possibility that the
      abnormality could explain some reports of degenerated myelinated fibers in sural
      nerve biopsies of patients with amyotrophic lateral sclerosis is underlined.

PMID- 7737019
TI  - Pediatric emergency medicine. The history of a growing discipline.
AB  - Pediatric emergency medicine is evolving into a more clearly described area of
      medical care. The historical development and future challenges of this
      subspecialty are discussed. In addition, emergency care for children is reviewed
      closely, citing differences in the pediatric populations seen in pediatric
      emergency departments and general emergency departments.

PMID- 7737020
TI  - Emergency medical services for children.
AB  - Emergency medical services for children require the integration of many community
      resources to operate optimally. In both urban and rural areas, the abilities of
      the receiving hospitals and medical staffs must be defined to develop a system
      that considers severity of injury and illness as well as transport times.

PMID- 7737021
TI  - An update on pediatric trauma.
AB  - Trauma care for children is examined from a demographic perspective. Critical
      issues, such as "who should care for acutely injured children" and "where should
      they receive care" are addressed. Specific issues regarding blunt trauma and
      indications for and outcome of emergency department thoracotomy are discussed
      also. A strategy for injury prevention is reviewed.

PMID- 7737022
TI  - Progress in pediatric cardiopulmonary resuscitation.
AB  - The success rate for cardiopulmonary resuscitation (CPR) in children is dismal.
      This review discusses the physiology of CPR, the basis for pharmacologic therapy,
      and the rationale for advanced interventions. It focuses attention on those areas
      in which research indicates hope for improved outcomes.

PMID- 7737023
TI  - Pediatric abuse. New patterns of injury.
AB  - The spectrum of abusive symptomatology has continued to expand since the initial
      report of the battered child syndrome. Many of these abused children present to
      the ED without a history of trauma. The ED physician must be aware of the range
      of clinical signs and symptoms to recognize and treat these children.

PMID- 7737024
TI  - The poisoned child. Evolving concepts in care.
AB  - More than 1 million children in the United States ingest poisons each year. The
      vast majority of these exposures result in no harm to the child. The task of the
      emergency physician is to discern which children are at risk and treat those
      children with appropriately aggressive therapy while minimizing intervention for
      the rest. In pediatric exposure cases, the toxin is usually identified. A careful
      toxic differential diagnosis will lead to a list of likely poisons in symptomatic
      patients without an identified exposure. The cornerstone of treatment remains the
      evaluation of the ingestion episode, careful assessment of the patient, and the
      application of basic supportive medical care. In the ED, when it has been
      determined that gastrointestinal decontamination is indicated on the basis of the
      substance and quantity ingested, activated charcoal is the decontamination agent
      of choice if the substance ingested is absorbed by activated charcoal. Gastric
      emptying should be restricted to those circumstances when the substance ingested
      is not bound to activated charcoal or the rare event when a child presents to the
      ED within 1 hour of ingestion with significant CNS depression. Whole bowel
      irrigation is a recently described technique to enhance the passage of drugs
      already beyond the pylorus. The indications for its use are poorly defined.
      Laboratory tests are generally overordered after pediatric ingestions.
      Appropriate use of the laboratory includes an assessment of basic serum chemistry
      studies in symptomatic patients, confirmation of suspected toxins, and the
      determination of the need for specific antidotal therapy. General "drug screens"
      are expensive and rarely contribute to patient care. Use of specific therapies,
      including antidotes and enhanced elimination techniques, should be limited to
      those cases when expectation that a defined benefit outweighs the risk of the
      procedure is reasonable. The indications for the use of these interventions in
      children may be different from those for adults.

PMID- 7737025
TI  - Analgesia, anesthesia, and conscious sedation.
AB  - Providing sedation and analgesia is an integral part of emergency care for
      children. To become facile at pediatric pain control and sedation, clinicians
      must develop expertise regarding proper monitoring, drugs and doses, potential
      side effects, and strategies to select the best agent for a given procedure and
      clinical setting. Currently available agents, methods, and monitoring guidelines
      are reviewed with an emphasis on conscious sedation.

PMID- 7737026
TI  - Occult bacteremia and septicemia in the febrile child younger than two years.
AB  - The literature on the assessment and the preferred treatment strategies for
      children without a focus of infection is reviewed. Opinions are offered regarding
      the diagnostic evaluation and therapeutic interventions for febrile infants and
      children who are at risk for occult bacteremia or sepsis. Clinicians are
      encouraged to consider the proposed strategies but not to supplant their
      prevailing practice.

PMID- 7737027
TI  - Central nervous system infections. The usual and the unusual.
AB  - The emergency physician must have an intentional approach to the child suspected
      of having meningitis. Emerging diagnostic tools and therapies, including the use
      of corticosteroids, are discussed. In addition, CNS infections that are less
      commonly seen are reviewed, including tuberculous meningitis and herpes simplex
      virus encephalitis.

PMID- 7737028
TI  - Otitis externa and otitis media. A new look at old problems.
AB  - Acute otitis media represents one of the most common presenting complaints seen
      among children in emergency departments. The pathophysiologic process and the
      infectious organisms are reviewed. Antibiotic choices are discussed, including a
      review of newer agents. An overview of otitis externa is provided also.

PMID- 7737029
TI  - Acute infectious enteritis in children. Emergency department diagnosis and
      management.
AB  - The approach to the child with acute infectious enteritis requires a clear
      diagnostic evaluation. The various common pathogens are reviewed. Treatment
      decisions are largely based on the clinical condition of the child. Oral
      rehydration therapy is addressed.

PMID- 7737030
TI  - New approaches to upper airway disease.
AB  - Although laryngotracheobronchitis is the most common upper respiratory tract
      disorder in pediatrics, several other diseases are potentially life-threatening.
      The emergency physician must recognize both the obvious and subtle distinctions
      among upper airway diseases. The status of the patient's airway remains the
      primary concern regardless of the suspected disorder, but further definitive care
      depends on the specific disease entity. The prompt recognition and action of both
      the prehospital care provider and the ED physician in maintaining a critical
      airway and supporting ventilation until definitive pediatric critical or surgical
      care can be delivered is essential in ensuring optimal outcome for children
      suffering from a life-threatening upper airway illness.

PMID- 7737031
TI  - Status epilepticus in children.
AB  - The emergency physician caring for children should have a thorough understanding
      of all aspects of SE. The morbidity and mortality attributable to this condition
      can be minimized through rapid recognition of the disorder, a rational
      therapeutic and diagnostic plan, and recognition and management of typical
      complications. Promising developments include new drugs, such as the phenytoin
      prodrug and the use of newer dosing methods and routes of administration for
      current drugs, such as very high-dose phenobarbital, thiopental barbiturate coma,
      and continuously infused midazolam.

PMID- 7737032
TI  - Pharmacokinetics: defining dosimetry for risk assessment. March 4-5, 1992,
      Washington, DC. Proceedings.

PMID- 7737033
TI  - Physiologic changes during growth and development.
AB  - To express growth-related changes in physiologic or other functions in forms
      usable for kinetic modeling, we are interested in identifying regular
      relationships that take the form of simple mathematical expressions. Many
      anatomic and physiologic functions scale within or across species in accordance
      with the allometric relationship, y = axb. These include many organ weights, the
      glomerular filtration rate, respiration rate, oxygen consumption, or basal
      metabolic rate. The allometric lines may display discontinuities in slope
      associated with critical growth periods such as transitions from one growth phase
      to another. On the other hand, many other kinetically important processes depend
      on the physiocochemical characteristics of the agent and of the sites in the body
      with which it interacts. Their rates of development are determined by the age
      dependence of these physiocochemical characteristics and of their interactions.
      Examples of different types of age-dependence are given, and their combined
      impact on the age-dependence of lead-kinetic behavior is examined.

PMID- 7737035
TI  - Pharmacokinetics in the child.
AB  - Pharmacokinetic studies have made many significant contributions to rational
      therapeutics in children. Pharmacokinetic data have helped distinguish between
      differences in drug disposition and drug sensitivity in children as compared to
      adults and led to the establishment of age-specific dosage guidelines. Factors
      influencing the observed differences between drug disposition in children and
      adults are reviewed. Specific examples utilizing anticancer drugs are presented.
      The use of model substrates to study hepatic drug metabolism and renal excretion
      in children is described and some results are discussed. The significance of
      genetic polymorphic drug metabolism is presented and the use of model substrates
      to determine individual metabolic phenotypes is described. The use of
      pharmacokinetic data to define the maximum-tolerated systemic exposure rather
      than the maximum-tolerated dosage of anticancer drugs in children is presented.

PMID- 7737034
TI  - Pharmacokinetics in the infant.
AB  - Processes controlling the absorption, distribution, metabolism, excretion, and
      pharmacologic effects of drugs are likely to be immature or altered in neonates
      and infants. Absorption may be affected by differences in gastric pH and stomach
      emptying rate. Low serum protein concentrations and higher body water composition
      can change drug distribution. Drug metabolism enzyme activity is typically
      reduced in the neonate, but rapidly develops over the first year of life. Renal
      excretion mechanisms are low at birth, but mature over a few months. Limited data
      are available on the pharmacodynamics of drugs; infants show greater sensitivity
      to d-tubocurarine. Developmental changes are rapid during the first weeks and
      months of life, thus requiring continual modification of drug dosage regimens
      designed for treating pediatric patients.

PMID- 7737036
TI  - Pharmacokinetics in the elderly.
AB  - Animals undergo substantial changes in many physiologic and biochemical functions
      as a natural consequence of aging. In the absence of disease or other pathologic
      conditions, these changes occur in a gradual manner with time (generally
      expressed as a fractional or percentage change in that function per year or
      decade). Furthermore, for any given function and at any given chronologic age,
      there is large variation in that function among individuals. Given the increase
      in life expectancy, the substantial increase in the number of elderly (and aged
      elderly) in the population, and the escalating costs of health care, there is
      great interest in learning more about the risks associated with aging as a result
      of toxic exposure. Are the elderly at greater risk than younger adults to the
      toxic effects of drugs and environmental exposure? Is the elderly population an
      inherently more sensitive one?

PMID- 7737037
TI  - Pharmacokinetic factors influencing risk assessment: saturation of biochemical
      processes and cofactor depletion.
AB  - Models generally consider risk to be a function of the hazard (toxicity) and
      exposure (dose). That function is best described by the dose response of the
      toxic effect. For any risk assessment system to be effective, it should consider
      that dose-response relationship. Saturation phenomena often produce nonlinear
      dose curves, and any risk assessment system should be able to address such
      effects. Physiologically based pharmacokinetics offer an approach to deal with
      these nonlinear responses. Some historic risk models and common saturable
      processes are discussed. The impact of maximum tolerated dose (MTD) on risk
      evaluation and the kinetics of some saturable processes are considered. Specific
      examples have been selected to demonstrate the importance of saturation of
      processes in assessing the hazard of chemicals.

PMID- 7737038
TI  - A carbamate insecticide: a case study of aldicarb.
AB  - Aldicarb, the active ingredient in the insecticide TEMIK, was introduced to the
      agricultural community over 25 years ago. It has been registered worldwide to
      control a wide variety of insect, mite, and nematode pests in agriculture. The
      toxicological research database supporting the registration and use of aldicarb
      was generated over more than 25 years and contains more than 280 animal studies
      on 12 species of animals, 2 clinical human trials, and over 20 human monitoring
      studies. This database, which includes biochemical aspects (metabolism and mode
      of-action studies), acute toxicity and special short-term toxicity studies, long
      term toxicity studies, and epidemiological observations in humans, serves as the
      starting point for the evaluation of the risks associated with the acceptance of
      levels of aldicarb residues in food and drinking water and for the more direct
      occupational exposure. This article highlights the available toxicological data
      and reviews worldwide regulation of aldicarb. Included in these discussions is a
      brief description of the toxicological end point upon which regulatory decisions
      have been based, namely acetylcholinesterase depression. Aldicarb, the N
      methylcarbamic acid ester of 2-methyl-2-(methylthio) propionaldehyde oxime, was
      the first of a limited group of insecticidal oxime N-methylcarbamates that have
      properties distinct from N-methylcarbamates which have a phenolic constituent,
      instead of the oxime moiety. Aldicarb is highly water-soluble (approximately 6000
      ppm), nonvolatile, relatively stable under acidic conditions, and is easily
      degraded under alkaline conditions. These properties are important determinants
      of its systemic action in plants and of its problematic environmental behavior.
      Possible environmental hazards involving the chemical include groundwater
      contamination and (more recently) excessive terminal residues in certain foods.

PMID- 7737039
TI  - Factors affecting mammary tumor incidence in chlorotriazine-treated female rats:
      hormonal properties, dosage, and animal strain.
AB  - Chlorotriazines are widely used in agriculture as broadleaf herbicides. The
      compounds specifically inhibit photosynthesis, and, as such, display little
      interaction with animal systems. However, a 24-month feeding study with atrazine
      (ATR) revealed a significant dose-related increase of mammary tumors in female
      Sprague-Dawley (SD) rats. Because numerous studies indicated that ATR had a low
      mutagenic and oncogenic potential, it was decided to test a hypothesis that the
      herbicide possessed endocrine activity. Among tests for estrogenic action, oral
      dosing of ATR up to 300 mg/kg did not stimulate uterine weight of ovariectomized
      rats. However, ATR administration did reduce estrogen-stimulated uterine weight
      gain. Further evidence of inhibition came from measures of [3H]-thymidine
      incorporation into uterine DNA of ATR-treated immature rats. Again, no intrinsic
      estrogenic activity was observed up to a 300-mg/kg dose. In vitro, ATR competed
      poorly against estradiol binding to cytosolic receptors, with an approximate IC50
      of 10(-5) M. Atrazine administration to SD and Fischer-344 (F-344) rats for 12
      months, up to 400 ppm in food, was correlated with significant alterations of
      estrous cycling activity; but there was a divergent strain response. SD rats
      showed an increased number of days in vaginal estrus, increased plasma estradiol,
      and decreased plasma progesterone by 9 to 12 months of treatment. F-344 rats did
      not demonstrate treatment-related affects. A study of ultrastructure in the
      hypothalamic arcuate nucleus of female SD rats that were fed
      diaminochlorotriazine (DACT), an ATR metabolite, suggested that age-associated
      glial pathology was enhanced by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737041
TI  - A tiered approach to pharmacokinetic studies.
AB  - Studies of absorption, distribution, metabolism, and elimination (ADME) have long
      been recognized as important in the evaluation of the pharmacological efficacy of
      pharmaceutical agents. In recent years, the importance of ADME studies in
      toxicology also has become increasingly apparent. In realization of the
      importance of ADME studies, regulatory agencies have established guidelines
      governing the conduct of these studies. To be of maximum utility, it is desirable
      that ADME and pharmacokinetic studies be closely integrated with the toxicity
      testing protocol. However, in many instances this is not the case, which results
      in ADME and pharmacokinetic studies that are often chronologically and
      philosophically remote from the toxicity testing protocols. An inevitable
      consequence of this approach is that it frequently leads to the generation of
      ADME data that are of limited use in the process of toxicity evaluation and risk
      assessment. Recently, there has been increased focus on developing testing
      strategies that would result in the development of ADME data with greater
      application to toxicity testing and risk assessment. An example of such an
      approach is the concept of a tiered approach to the conduct of ADME studies. An
      important aspect of the tiered approach is generating ADME data at an earlier
      stage during the toxicity testing of a chemical. This could be effected by
      acceptance of the concept of a minimum experimental data set for a chemical. This
      minimum data set could be conducted in a timely and economic manner and would
      develop data addressing three fundamental questions: Is the chemical absorbed? Is
      the chemical metabolized? Does the chemical persist?(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7737040
TI  - Applications of physiologic pharmacokinetic modeling in carcinogenic risk
      assessment.
AB  - The use of physiologically based pharmacokinetic (PBPK) models has been proposed
      as a means of estimating the dose of the reactive metabolites of carcinogenic
      xenobiotics reaching target tissues, thereby affording an opportunity to base
      estimates of potential cancer risk on tissue dose rather than external levels of
      exposure. In this article, we demonstrate how a PBPK model can be constructed by
      specifying mass-balance equations for each physiological compartment included in
      the model. In general, this leads to a system of nonlinear partial differential
      equations with which to characterize the compartment system. These equations then
      can be solved numerically to determine the concentration of metabolites in each
      compartment as functions of time. In the special case of a linear pharmacokinetic
      system, we present simple closed-form expressions for the area under the
      concentration-time curves (AUC) in individual tissue compartments. A general
      relationship between the AUC in blood and other tissue compartments is also
      established. These results are of use in identifying those parameters in the
      models that characterize the integrated tissue dose, and which should therefore
      be the primary focus of sensitivity analyses. Applications of PBPK modeling for
      purposes of tissue dosimetry are reviewed, including models developed for
      methylene chloride, ethylene oxide, 1,4-dioxane, 1-nitropyrene, as well as
      polychlorinated biphenyls, dioxins, and furans. Special considerations in PBPK
      modeling related to aging, topical absorption, pregnancy, and mixed exposures are
      discussed. The linkage between pharmacokinetic models used for tissue dosimetry
      and pharmacodynamic models for neoplastic transformation of stem cells in the
      target tissue is explored.

PMID- 7737042
TI  - Physiologically based pharmacokinetic model for the inhibition of
      acetylcholinesterase by organophosphate esters.
AB  - Organophosphate (OP) exposure can be lethal at high doses while lower doses may
      impair performance of critical tasks. The ability to predict such effects for
      realistic exposure scenarios would greatly improve OP risk assessment. To this
      end, a physiologically based model for diisopropylfluorophosphate (DFP)
      pharmacokinetics and acetylcholinesterase (AChE) inhibition was developed. DFP
      tissue/blood partition coefficients, rates of DFP hydrolysis by esterases, and
      DFP-esterase bimolecular inhibition rate constants were determined in rat tissue
      homogenates. Other model parameters were scaled for rats and mice using standard
      allometric relationships. These DFP-specific parameter values were used with the
      model to simulate pharmacokinetic data from mice and rats. Literature data were
      used for model validation. DFP concentrations in mouse plasma and brain, as well
      as AChE inhibition and AChE resynthesis data, were successfully simulated for a
      single iv injection. Effects of repeated, subcutaneous DFP dosing on AChE
      activity in rat plasma and brain were also well simulated except for an apparent
      decrease in basal AChE activity in the brain which persisted 35 days after the
      last dose. The psychologically based pharmacokinetic (PBPK) model parameter
      values specific for DFP in humans, for example, tissue/blood partition
      coefficients, enzymatic and nonenzymatic DFP hydrolysis rates, and bimolecular
      inhibition rate constants for target enzymes were scaled from rodent data or
      obtained from the literature. Good agreement was obtained between model
      predictions and human exposure data on the inhibition of red blood cell AChE and
      plasma butyrylcholinesterase after an intramuscular injection of 33 micrograms/kg
      DFP and at 24 hr after acute doses of DFP (10-54 micrograms/kg), as well as for
      repeated DFP exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737043
TI  - Parameter variability and the interpretation of physiologically based
      pharmacokinetic modeling results.
AB  - For the past several years we have been working with models of benzene
      distribution and metabolism, principally in the rat, but more recently in humans.
      Our biologically related objectives have been primarily to assist our laboratory
      based colleagues in their quest for understanding of the mechanisms by which
      benzene exerts its toxic action. A secondary goal has been to develop or adapt
      models useful in risk assessment applications. We have also had methodological
      goals that relate to applications of sensitivity analysis on the one hand, but
      more fundamentally to the connection between experimental data and model
      structure and parameterization. This paper presents an overview of our work in
      these areas.

PMID- 7737045
TI  - Influence of metabolism in skin on dosimetry after topical exposure.
AB  - Metabolism of chemicals occurs in skin and therefore should be taken into account
      when one determines topical exposure dose. Skin metabolism is difficult to
      measure in vivo because biological specimens may also contain metabolites from
      other tissues. Metabolism in skin during percutaneous absorption can be studied
      with viable skin in flow-through diffusion cells. Several compounds metabolized
      by microsomal enzymes in skin (benzo[a]pyrene and 7-ethoxycoumarin) penetrated
      human and hairless guinea pig skin predominantly unmetabolized. However,
      compounds containing a primary amino group (p-aminobenzoic acid, benzocaine, and
      azo color reduction products) were substrates for acetyltransferase activity in
      skin and were substantially metabolized during absorption. A physiologically
      based pharmacokinetic model has been developed with an input equation, allowing
      modeling after topical exposure. Plasma concentrations in the hairless guinea pig
      were accurately predicted for the model compound, benzoic acid, from in vitro
      absorption, metabolism, and other pharmacokinetic parameters.

PMID- 7737044
TI  - Uptake and metabolism of toxicants in the respiratory tract.
AB  - The sites of uptake and retention of inhalants within the respiratory tract
      influence which tissues are susceptible to damage. Physical and chemical
      properties of inhalants, including size, water:air and oil:water partition
      coefficients, and reactivity or susceptibility to metabolism are the major
      factors that affect deposition and retention. The high metabolic capacity of the
      cells of the olfactory tissue and bronchiolar Clara cells contributes to their
      susceptibility to damage from both inhaled and bloodborne toxicants. The major
      enzymes that metabolize pesticides and many other potential toxicants are the
      cytochrome P450 and flavin-containing monooxygenases and the carboxylesterases.

PMID- 7737046
TI  - Role of renal metabolism in risk to toxic chemicals.
AB  - The kidneys are capable of carrying out extensive oxidation, reduction,
      hydrolysis, and conjugation reactions. Renal cortex has high activities of
      cytochrome P450 and glutathione (GSH) S-transferase. In contrast, renal medulla
      has high activity of prostaglandin synthetase, which can catalyze co-oxidation of
      xenobiotics. While these pathways are found in many tissues and at higher
      activities than in kidney, several key enzymes of the mercapturic acid pathway
      are found at especially high activities in cells of the renal proximal tubule.
      Investigations over the last two decades demonstrated that GSH conjugation is not
      only a mechanism for detoxification of reactive electrophiles. Rather, metabolism
      of GSH S-conjugates to the corresponding cysteine S-conjugates represents a
      branch point: cysteine S-conjugates may be metabolized by the cysteine S
      conjugate N-acetyl-transferase to mercapturic acids, which are nontoxic and are
      excreted, or they may be substrates for the pyridoxal phosphate-dependent
      cysteine conjugate beta-lyase, which catalyzes either a beta-elimination or a
      transamination reaction to produce unstable thiols. These thiols rearrange to
      form potent acylating species that can covalently bind to cellular
      macromolecules, thereby producing cytotoxicity, mutagenicity, and
      carcinogenicity. In addition to the beta-lyase, two other renal enzymes, L-2
      amino (2-hydroxy) acid oxidase and cysteine conjugate S-oxidase, can bioactivate
      chemicals to produce nephrotoxic species. Several halogenated alkanes and alkenes
      are bioactivated by these pathways. These findings show that mammalian kidney is
      highly active in bioactivation of xenobiotics. Although the properties of the
      corresponding enzymes in humans may differ, it is clear that renal metabolism can
      be a critical determinant of risk to chemical injury.

PMID- 7737048
TI  - Chemical contaminants, pharmacokinetics, and the lactating mother.
AB  - We review the commonly occurring persistent pesticides and industrial chemicals
      in breast milk. These chemicals are dichlorodiphenyl trichloroethane as
      dichlorodiphenyl dichloroethene dieldrin, chlordane as oxychlordane, heptachlor,
      polychlorinated biphenyls, polychlorinated dibenzofurans, and polychlorinated
      dibenzodioxins. We present a worked example of the kinds of pharmacokinetic
      assumptions and calculations necessary for setting regulatory limits of
      contaminants in the food supply, calculating dose of chemical contaminants to the
      nursed infant, converting risks from lifetime exposure in laboratory animals to
      risks for short-term exposure in humans, and estimating the excess cancer risk to
      the nursed infant.

PMID- 7737050
TI  - Fighting for air.

PMID- 7737051
TI  - Safe to eat.

PMID- 7737049
TI  - Pharmacokinetic determinants of embryotoxicity in rats associated with organic
      acids.
AB  - We have studied four organic acids of similar structure to further understand the
      basis of their developmental toxicity. Valproic acid (2-propyl pentanoic acid),
      ethylhexanoic acid, and octanoic acid are isomeric C8 organic acids but their
      teratologic potency varied widely. Valproic acid induced a moderate to severe
      teratologic outcome after a single oral administration of 6.25 mmoles/kg on day
      12 of rat pregnancy. Twice as much ethylhexanoic acid (12.5 mmoles/kg) induced a
      less severe response. Octanoic acid was nonteratogenic even at the very high dose
      of 18.75 mmoles/kg. This latter result is undoubtedly due to poor intestinal
      absorption of octanoic acid, as the maternal plasma levels never reached half of
      those measured for valproic acid and ethylhexanoic acid. Moreover, only a tiny
      fraction of that in maternal plasma was actually transferred into the embryo. On
      the other hand, the peak concentration and duration of exposure to valproic acid
      and ethylhexanoic acid were very similar despite a more severe teratologic
      outcome following valproic acid, which indicated higher intrinsic activity of
      this latter agent. A fourth agent, methylhexanoic acid, was also studied and had
      no teratogenic effects when given at 14.1 mmoles/kg. Pharmacokinetic studies of
      this agent revealed higher peak concentrations in maternal plasma and embryo than
      valproic acid or ethylhexanoic acid, but the duration of exposure was shorter. We
      conclude that pharmacokinetic parameters can be important determinants of
      teratologic outcome and thereby help explain differing potencies of structurally
      similar chemicals.

PMID- 7737047
TI  - Pharmacogenetics: detecting sensitive populations.
AB  - Risk assessment models strive to predict risks to humans from toxic agents.
      Safety factors and assumptions are incorporated into these models to allow a
      margin of error. In the case of cancer, substantial evidence shows that the
      carcinogenic process is a multistage process driven by the interaction of
      exogenous carcinogenic exposures, genetic traits, and other endogenous factors.
      Current risk assessment models fail to consider genetic predispositions that make
      people more sensitive or resistant to exogenous exposures and endogenous
      processes. Several cytochrome P450 enzymes, responsible for metabolically
      activating carcinogens and medications, express wide interindividual variation
      whose genetic coding has now been identified as polymorphic and linked to cancer
      risk. For example, a restriction fragment-length polymorphism for cytochrome
      P4501A1, which metabolizes polycyclic aromatic hydrocarbons, and cytochrome
      P4502E1, which metabolizes N-nitrosamines and benzene, is linked to lung cancer
      risk. Cytochrome P4502D6, responsible for metabolizing many clinically important
      medications, also is linked to lung cancer risk. The frequency for each of these
      genetic polymorphisms vary among different ethnic and racial groups. In addition
      to inherited factors for the detection of sensitive populations, determining the
      biologically effective doses for carcinogenic exposures also should
      quantitatively and qualitatively enhance the risk assessment process. Levels of
      carcinogen-DNA adducts reflect the net effect of exposure, absorption, metabolic
      activation, detoxification, and DNA repair. These effects are genetically
      predetermined, inducibility notwithstanding. The combination of adduct and
      genotyping assays provide an assessment of risk that reflects recent exogenous
      exposure as well as one's lifetime ability to activate and detoxify carcinogens.

PMID- 7737053
TI  - The waning war on cancer.

PMID- 7737052
TI  - French fry fuel.

PMID- 7737054
TI  - Dioxin review blues.

PMID- 7737055
TI  - Mismatch Mania.

PMID- 7737056
TI  - Falk Lecture gives overview of breast cancer.

PMID- 7737057
TI  - Environmental Awareness at NIEHS.

PMID- 7737058
TI  - NTP announces bioassay results.

PMID- 7737059
TI  - Strange brew: assessing risk of chemical mixtures.

PMID- 7737060
TI  - Science in the court.

PMID- 7737061
TI  - Labs online: research on the Internet.

PMID- 7737062
TI  - Crystalline silica: risks and policy.
AB  - Since the International Agency for Research on Cancer labeled crystalline silica
      a probable carcinogen in 1988, government regulations have required sand and
      other products to contain warning labels and researchers have attempted to
      quantitatively assess low-exposure risks. The uncertainties are unlikely to
      diminish any time soon, and little value exists in calculating such risks, as low
      exposures to this ubiquitous mineral are commonplace in both urban and rural
      areas due to many uncontrollable activities. What is certain is that regulatory
      resources targeted at continuing high-level occupational exposures would be much
      more likely to have beneficial public health consequences than continued attempts
      to assess low-exposure risks quantitatively.

PMID- 7737063
TI  - Tobacco and cancer: epidemiology and the laboratory.
AB  - Tobacco smoke contains many mutagenic and carcinogenic chemicals. Both whole
      tobacco smoke and extracts induce tumors in experimental animals. Work with
      carcinogen-macromolecule adducts provided evidence for the action of specific
      chemicals. Molecular epidemiology studies suggested that point mutations in tumor
      suppressor genes (e.g., p53) and oncogenes (e.g., ras) may be specific both for
      the type of tumor and for the critical environmental exposure. The consistency
      among investigations on oncogene/tumor-suppressor gene mutations in lung cancer
      (and other tobacco-related cancers) in smokers is highly suggestive, although we
      still lack information about the time sequence between exposure, gene mutation,
      and cancer onset. Current work that deserves emphasis includes investigations
      revealing that lungs of smokers contain benzo[a]pyrene diol-epoxide-guanine DNA
      adducts, which are in accordance with the type of mutations found in K-ras or p53
      genes (G to T transversions). In addition, DNA in human exfoliated bladder cells
      showed a derivative of 4-aminobiphenyl as a main adduct; there was also an
      association between smoking habits (amount and type of tobacco) and the levels of
      both DNA adducts and hemoglobin adducts formed by aromatic amines. Increasing
      evidence indicates that genetically based metabolic polymorphisms exert a role in
      modulating individual susceptibility to the action of tobacco carcinogens.
      Overall, the weight of evidence strongly supports the causal nature of the
      association between smoking and cancer and falsifies Fisher's hypothesis that the
      association was due to confounding by genetic predisposition.

PMID- 7737064
TI  - Contaminant-related suppression of delayed-type hypersensitivity and antibody
      responses in harbor seals fed herring from the Baltic Sea.
AB  - Recent mass mortalities among several marine mammal populations have led to
      speculation about increased susceptibility to viral infections as a result of
      contaminant-induced immunosuppression. In a 2.5-year study, we fed herring from
      either the relatively uncontaminated Atlantic Ocean or the contaminated Baltic
      Sea to two groups of captive harbor seals and monitored immune function in the
      seals. Seals fed the contaminated fish were less able to mount a specific
      immunological response to ovalbumin, as measured by in vivo delayed-type
      hypersensitivity (DTH) reactions and antibody responses. The skin reaction to
      this protein antigen was characterized by the appearance of mononuclear cells
      which peaked at 24 hr after intradermal administration, characteristic of DTH
      reactions in other animals studied. These DTH responses correlated well with in
      vitro tests of T-lymphocyte function, implicating this cell type in the reaction.
      Aryl-hydrocarbon (Ah) receptor-dependent toxic equivalent (TEQ) profiles in
      blubber biopsies taken from the seals implicated polychlorinated biphenyls rather
      than dioxins or furans in the observed immunosuppression. Marine mammal
      populations currently inhabiting polluted coastal environments in Europe and
      North America may therefore have an increased susceptibility to infections, and
      pollution may have played a role in recent virus-induced mass mortalities.

PMID- 7737065
TI  - Decline in liver neoplasms in wild brown bullhead catfish after coking plant
      closes and environmental PAHs plummet.
AB  - Polycyclic aromatic hydrocarbons (PAHs) in both sediment and brown bullhead
      catfish tissues from the Black River in Lorain County, Ohio, declined by 65% and
      93%, respectively, between 1980 and 1982. Sediment PAHs declined an additional
      99% by 1987, coincident with the closure of a coking facility in 1983.
      Contemporaneously, liver cancer in 3- to 4-year-old brown bullheads declined to
      about one-quarter the 1982 frequency (10% versus 39%) by 1987, while the
      percentage of livers without any proliferative lesions doubled (42% versus 20%).
      These changes were significant within age group. Our data affirm a cause-and
      effect relationship between PAH exposure and liver cancer in wild fish. The data
      also support the efficacy of natural, unassisted remediation once the source of
      the pollution is eliminated.

PMID- 7737066
TI  - A technique to expose animals to concentrated fine ambient aerosols.
AB  - This paper presents the development and evaluation of an ambient particle
      concentrator for conducting animal inhalation exposure studies. The system
      utilizes the principle of virtual impactors to concentrate ambient particles in
      the size range 0.1-2.5 microns (aerodynamic diameter; dp) by drawing them through
      a series of three virtual impactors. Each impactor contains the majority of
      ambient fine mass (dp < 2.5 microns aerodynamic diameter) in a bleed flow (minor
      flow) that is 20% of the total flow entering the virtual impactor. The virtual
      impactors have been characterized using indoor air samples as test aerosols. Fine
      mass and sulfate concentrations at the outlet of the concentrating system were
      compared to the ambient fine mass and sulfate levels, which were determined using
      Harvard-Marple impactors. In each of the stages, particle concentration was
      increased by a factor of approximately 3. Thus, an overall concentration factor
      of about 25-30 was achieved. The main goal of this study was to demonstrate the
      feasibility of conducting animal exposures using the newly developed ambient fine
      particle concentrator.

PMID- 7737067
TI  - A retrospective evaluation of COMPACT predictions of the outcome of NTP rodent
      carcinogenicity testing.
AB  - The carcinogenic potentials of 40 National Toxicology Program chemicals
      previously predicted by Computer Optimised Molecular Parametric Analysis for
      Chemical Toxicity (COMPACT), based on the identification of potential substrates
      of cytochromes P4501A and 2E (CYP1A and CYP2E), have been compared with new
      rodent carcinogenicity results. The COMPACT predictions have also been compared
      with published Ames mutagenicity data and with our own Hazardexpert predictions
      for carcinogenicity. Concordance evaluations between rodent carcinogenicity (1/4
      segments positive) and predictions by COMPACT or Hazardexpert were 64% for
      COMPACT (CYP1A only), 72% for COMPACT (CYP1A plus CYP2E), 70% for Hazardexpert
      alone, and 86% for COMPACT (CYP1A plus CYP2E) plus Hazardexpert. Sensitivities of
      the predictions were for COMPACT, 75%; Hazardexpert, 60%; and Ames, 54%. Positive
      predictivities were for COMPACT, 75%; Hazardexpert, 78%; and Ames 81%. Negative
      predictivites were for COMPACT, 62%; Hazardexpert, 52%; and Ames, 42%.

PMID- 7737068
TI  - A preliminary evaluation of the cognitive and motor effects of pediatric HIV
      infection in Zairian children.
AB  - Fourteen asymptomatic HIV-infected Zairian children under 2 years of age
      displayed social and motor developmental deficits on the Denver Developmental
      Screening Test when compared with 20 HIV-negative cohorts born to HIV-infected
      mothers and 16 control children. In a second study, 11 infected children over 2
      years of age had sequential motor and visual-spatial memory deficits on the
      Kaufman Assessment Battery for Children and motor development deficits on the
      Early Childhood Screening Profiles. HIV infection affects central nervous system
      structures mediating motor and spatial memory development, even in seemingly
      asymptomatic children. Furthermore, maternal HIV infection compromises the labor
      intensive provision of care in the African milieu and undermines global cognitive
      development in even uninfected children.

PMID- 7737069
TI  - Multiple sexual partners and their psychosocial correlates: the population-based
      AIDS in multiethnic neighborhoods (AMEN) study.
AB  - In this study we examined multiple partners in a household probability sample of
      heterosexuals. Thirty-seven percent reported 2 or more partners in the past year,
      and 6% reported 5 or more partners. Significant interactions among gender,
      ethnicity, and relationship status revealed complex relations. African American
      men without a primary partner were the most likely to have multiple partners;
      ethnic minority women with primary partners were the least likely. Psychosocial
      factors associated with multiple partners were examined with the AIDS Risk
      Reduction Model (ARRM). Situational factors influenced how ARRM variables related
      to multiple partners. Perceived risk, commitment to monogamy, and communication
      were all important correlates. Prevention efforts must focus on increasing
      awareness of the risks of heterosexual transmission of HIV for people in dating
      relationships and on strengthening sexual communication skills with new partners.

PMID- 7737070
TI  - Children's perceptions of smokers and nonsmokers: a longitudinal study.
AB  - In a longitudinal study we investigated 5th- and 7th-grade children's perceptions
      of smokers and nonsmokers, changes in perceptions from 5th to 7th grades, and the
      degree to which these perceptions predict smoking in 9th grade. The participants
      were 1,663 students from 14 school districts in Washington state. The results
      showed large developmental shifts from 5th to 7th grade in children's perceptions
      of both smokers and nonsmokers: Students at 7th grade saw smokers in a much more
      positive light and nonsmokers in a much more negative light than they did at 5th
      grade. Children's positive perceptions at 5th grade of smokers predicted smoking
      4 years later at 9th grade and were stronger predictors than positive perceptions
      at 7th grade. The results suggest that smoking prevention interventions must
      begin before 5th grade to counter perceptions predictive of subsequent smoking.

PMID- 7737071
TI  - Research on disclosure of HIV status: cultural evolution finds an ally in
      science.
AB  - This editorial responds to Mason et al.'s (1995) "Culturally Sanctioned Secrets:
      Latino Men's Nondisclosure of HIV Infection to Family, Friends, and Lovers."
      Culture is an evolving dynamic phenomenon shaped by society, psychology, and
      history. Historically, familism and simpatia have been Hispanic cultural assets.
      As times change, however, values and behaviors that served a culture for
      generations may become liabilities unless they evolve to fit the changing world
      of the culture. In the case of Hispanic gay men, the desire to protect family
      members is a barrier to disclosure of HIV status. Mason et al.'s study points to
      areas in which cultural development is needed. Science and culture thus become
      allies, with science pointing the way to needed directions for adaptive cultural
      evolution.

PMID- 7737072
TI  - Programmed therapeutic messages as a smoking treatment adjunct: reducing the
      impact of negative affect.
AB  - Maintaining treatment gains remains a challenge to smoking cessation programs.
      Smokers prone to negative affect are most likely to relapse. In an effort to
      improve maintenance, a standard cognitive-behavioral treatment was supplemented
      with the provision of computer-controlled audiotape players containing
      personalized therapeutic messages. Either the standard treatment alone, or the
      standard treatment plus 2 months use of the tape player were provided to 41
      smokers. No outcome difference was found between the 2 conditions during the 1
      year follow-up. (The combined 1-year abstinence rate was 61%, with 34%
      continuously abstinent.) The frequency with which participants used the device
      predicted both posttreatment coping skill use and smoking rate. Most notable was
      an interaction between treatment condition and negative affect. Provision of the
      devices negated or reversed the usual association between negative affect and
      poorer outcome.

PMID- 7737073
TI  - Gender and ethnicity in children's cardiovascular reactivity: 7 years of study.
AB  - A total of 295 children (127 White boys, 15 Black boys, 133 White girls, and 20
      Black girls) participated in reactivity examinations in 1987 (all were in 3rd
      grade; age, M = 9.1 years), 1988, 1989, 1991, 1992 and 1993 (all were in 9th
      grade; age, M = 15.1 years). An analysis of residualized reactivity change values
      indicated consistent and significant ethnicity effects (Blacks greater than
      Whites) for systolic and diastolic blood pressure and for heart rate. Gender
      effects were also apparent for both systolic and diastolic blood pressure (boys
      greater than girls). These data suggest that the transition from childhood to
      adolescence is associated with a significant pattern of ethnic differences in
      reactivity, although the association of this pattern with the development of
      cardiovascular risk and disease remains to be ascertained.

PMID- 7737074
TI  - Changing inaccurate perceptions of health risk: results from a randomized trial.
AB  - We sought to identify and correct inaccurate perceptions of risk among 1,317
      adult patients in a primary care setting. Patients' perceived risks of heart
      attack, stroke, cancer, and motor vehicle crash were assessed and compared with a
      measure of risk derived from a health risk appraisal. Patients were then randomly
      assigned to receive computer-generated individualized risk feedback, risk
      feedback plus behavioral change feedback, or no feedback. Changes in perceived
      risk from baseline to a 6-month follow-up were compared across study groups.
      Results showed that individualized risk feedback was effective in increasing
      perceived stroke risk among patients who had underestimated their stroke risk at
      baseline and in reducing perceived risk of cancer among patients who had
      overestimated their cancer risk at baseline. Individualized risk feedback did not
      alter patients' perception of their heart attack and motor vehicle crash risks.

PMID- 7737075
TI  - Culturally sanctioned secrets? Latino men's nondisclosure of HIV infection to
      family, friends, and lovers.
AB  - Spanish-speaking Latino men (n = 107) were more likely than English-speaking
      Latinos (n = 85) and Whites (n = 206) to withhold their HIV-positive serostatus
      and their gay or bisexual orientation from significant others, especially family
      members. Similar effects were observed when Latinos were divided by birthplace
      and when analyses controlled for sociodemographic and medical factors. Reasons
      for revealing or concealing an HIV diagnosis varied across targets. Although both
      Latinos and Whites were more likely to withhold their diagnosis from their
      parents to prevent worrying them than to avoid personal rejection, this tendency
      was somewhat stronger among Latinos. Our findings suggest that some traditional
      values may deter Latinos from seeking HIV-related social support in times of
      need.

PMID- 7737076
TI  - On babies and bathwater: disease impact and negative affectivity in the self
      reports of persons with rheumatoid arthritis.
AB  - The degree to which self-reports of health and functioning reflect negativity
      (NA), a dispositional tendency to emphasize the negative, was examined with data
      from a 7-year longitudinal study of adaptation to rheumatoid arthritis. Principal
      component analyses performed on each of 8 waves of data consistently indicated
      that the dominant factor in these data was defined by measures of pain and
      functional impairment. In the final wave, Disease Impact, a scale derived from
      this component, was directly compared to NA. The 2 scales demonstrated
      considerable discriminant validity, and most of the significant intercorrelations
      among Disease Impact and the other variables examined remained statistically
      significant after the influence of NA was partialed out. These results suggest
      that reports of pain, impairment, and associated variables reflected disease
      related outcomes and processes and not simply NA.

PMID- 7737077
TI  - Positive expectations predict health after heart transplantation.
AB  - We explored the relations between positive expectations and adjustment,
      adherence, and health in cardiac transplant patients. Thirty-one patients and
      their nurse completed questionnaires before transplantation and at 3 times after
      surgery. As predicted, patients' self-reported positive expectations were
      generally associated with good mood, adjustment to the illness, and quality of
      life, even in patients who experienced health setbacks. High preoperative
      expectations predicted later adherence to a complex medical regimen. Positive
      expectations measured before the transplant predicted a substantial amount of the
      variance in the nurse's ratings of physical health 6 months after surgery,
      covarying for adherence behavior and preoperative health.

PMID- 7737078
TI  - Understanding readiness for regular physical activity in older individuals: an
      application of the theory of planned behavior.
AB  - This study examined whether stage of readiness for regular physical activity
      (i.e., discrete phases from inactive to active) was related to beliefs concerning
      perceived social pressure, attitude, perceived control, and intention. Data were
      collected from 288 older people through the mail. Frequency data indicated that
      over 50% of the sample had been engaging in regular physical activity for longer
      than 6 months. Analysis of variance (ANOVA) results showed that all selected
      variables shared significant variance with stage of readiness, and discrimination
      among the stages by the selected variables was successful. Path analysis
      indicated that intention, attitude, and perceived control had direct
      relationships with stage of readiness. Discussion focused on the utility of these
      variables for understanding individual differences in stage of readiness for
      regular physical activity.

PMID- 7737079
TI  - Major depression and medication adherence in elderly patients with coronary
      artery disease.
AB  - Little is known about the effects of depression on adherence to medical treatment
      regimens in older patients with chronic medical illnesses. Poor adherence may
      explain the increased risk of medical morbidity and mortality found in depressed
      medical patients. Ten of 55 patients over the age of 64 with coronary artery
      disease met the criteria for major depression from the Diagnostic and Statistical
      Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association,
      1987). All patients were prescribed a twice-per-day regimen of low dose aspirin
      to reduce their risk for myocardial infarction. Medication adherence was assessed
      for 3 weeks by an unobtrusive electronic monitoring device. Depressed patients
      adhered to the regimen on 45% of days, but nondepressed patients, on 69% (p <
      .02). Thus, major depression is associated with poor adherence to a regimen of
      prophylactic aspirin after the diagnosis of coronary artery disease.

PMID- 7737080
TI  - Pulsed field separation of large supercoiled and open-circular DNAs and its
      application to bacterial artificial chromosome cloning.
AB  - We have studied the separation of large (80-300 kbp) supercoiled (SC) DNA in
      conventional agarose gel electrophoresis, field inversion gel electrophoresis
      (FIGE) and pulsed field gel electrophoresis (PFGE). DNA migration was measured
      under a variety of electrophoretic conditions including different switch times,
      temperatures, agarose concentrations, and voltage gradients. The migration of SC
      DNA was found to be inversely proportional to its molecular weight in the three
      electrophoresis systems tested. In conventional agarose electrophoresis, voltage
      gradient was found to be the determining parameter in the separation of SC DNA.
      Unlike large linear DNAs, the migration of SC DNA was found to be independent of
      switch time in PFGE and FIGE. Broad DNA bands were observed in prolonged FIGE
      runs. In addition, we have also studied the migration of open-circular (OC) DNA
      (80 and 100 kbp) in pulsed field gel electrophoresis. Eighty kbp OC DNA can
      migrate into agarose gels under certain pulsed field conditions whereas 100 kbp
      OC DNA was trapped at the wells. Based on electrophoretic conditions described in
      this report, we can determine the size of bacterial artificial chromosome (BAC)
      clones without restriction enzyme digestion and have enriched the percentage of
      larger size clones in BAC cloning.

PMID- 7737081
TI  - High-resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      immunochemical identification of the 2X and embryonic myosin heavy chains in
      complex mixtures of isomyosins.
AB  - In mammals myosin heavy chains (MHC) are polypeptides with a molecular mass of
      about 200 kDa whose isoforms can be identified by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and immunochemistry.
      Electrophoretic analysis is the only method for quantitating MHC profiles in
      single myofibers and/or cryostat sections of biopsied muscle. We present a method
      for SDS-PAGE of adult rat skeletal muscle which resolves MHC into four bands: 1,
      2B, 2X, and 2A from the faster to the slower migrating band. Furthermore,
      embryonic MHC can be also resolved in a complex mixture of isomyosins, e.g.
      developing or regenerating muscles. The method does not involve preparation of
      gradient gels or electrophoresis at low temperature. Improved reproducibility is
      obtained by: (i) modification of the sample buffer; (ii) use of 7% polyacrylamide
      in the separating gel; (iii) control of pH of running buffer by recirculation or
      change of the buffer during the run; and (iv) a 24 h run. The procedure is
      compatible with Coomassie Brilliant Blue, silver and immunoblot staining.
      Resolution is sufficient to permit transblotting of separated MHC after SDS-PAGE.
      The different isoforms are easily identified with monoclonal antibodies. The
      technique provides an improved method to separate MHC and quantitate MHC2X and
      MHCemb in complex mixtures of MHC from a few cryostat sections of normal and
      diseased muscle.

PMID- 7737082
TI  - Species identification of cyst and root-knot nematodes from potato by
      electrophoresis of individual females.
AB  - To carry out rapid and reliable species identification of Globodera and
      Meloidogyne specimens, two electrophoretic methods were modified and adapted for
      an automated electrophoresis system (PhastSystem, Pharmacia). Proteins of
      individual Globodera cysts were identified using isoelectric focusing and a
      sensitive silver stain. Proteins of young single Meloidogyne females were
      separated using polyacrylamide gradient gels and stained for the isozymes
      esterase and malate dehydrogenase.

PMID- 7737083
TI  - Ogston gel electrophoretic sieving: how is the fractional volume available to a
      particle related to its mobility and diffusion coefficient(s)?
AB  - The Ogston-Morris-Rodbard-Chrambach model (OMRCM) of gel electrophoresis assumes
      that the mobility mu of charged particles is proportional to the fractional
      volume (f) of the gel that is available to them. If the gel is random, as
      described by Ogston, the (semi-log) Ferguson plot is the method of choice for
      analyzing experimental data since it permits an estimate of the gel's mean pore
      size to be made. However, the Ferguson plot is rarely linear; this is usually
      "explained" by the deformation of the anisotropy of the particle, the nonrandom
      or variable architecture or the gel, or the onset of some other migration
      mechanism. Many authors have refined this model, but the original assumption that
      mu varied; is directly proportional to f has not been seriously examined. Also,
      the model says nothing of the effect of the field intensity, the connectivity of
      the gel pores, nor anything about the diffusion coefficient. We have developed a
      Monte-Carlo computer simulation algorithm to study the electrophoretic sieving of
      simple particles in gels. In this brief communication, we report important
      preliminary results which indicate that the basic assumptions of the OMRCM are
      wrong. We use a two-dimensional periodic gel since the OMRCM becomes trivial in
      this case. Our results show that the relationship between f and mu is not the one
      assumed by the OMRCM. Moreover, we find that the Einstein relation between the
      diffusion coefficient and the mobility is not valid. This is due to the fact that
      the particles do not have a uniform probability of visiting the various sites
      that are available to them. We thus conclude that the Ferguson plot is
      intrinsically nonlinear; the curvature of the plot is, in fact, related to the
      intensity of the electric field as well as to the degree of randomness of the gel
      fibers.

PMID- 7737084
TI  - High resolution one-dimensional electrophoretic separation and partial
      characterisation of human head hair proteins.
AB  - A reproducible, rapid procedure for the extraction, labelling and separation of
      human hair proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) has been developed. Hair proteins were extracted in 8 M urea,
      containing 0.2 M mercaptoethanol, followed by sonication. Extracts were
      neutralised with Tris and incubated with either labelled (14C) or unlabelled
      iodoacetic acid to S-carboxymethylate cysteine groups. Proteins were separated on
      12.5% SDS-polyacrylamide gels and gels stained with Coomassie Brilliant Blue
      and/or silver nitrate to reveal major protein bands. Gels were then treated with
      a fluorographic agent, dried and autoradiographed to reveal major sites of S
      carboxymethylation. A given gel was scanned by laser densitometry after Coomassie
      and/or silver stain to quantitate the protein content of each major protein zone.
      An autoradiogram of the same gel was scanned to estimate the cysteine content of
      each major zone. In this way it was possible to partially characterise rapidly
      and reproducibly many different protein zones in different individual samples on
      one gel at the same time. By calculating the ratio of autoradiograph absorbance
      to Coomassie Blue absorbance, protein zones could be assigned to four different
      categories, viz: very high cysteine (VHC) proteins, high cysteine (HC) proteins,
      low cysteine (LC) proteins and very low cysteine (VLC) proteins. The method
      described is reproducible, rapid and inexpensive enough to be suitable for mass
      screening. Overall the results were more informative than previously reported one
      dimensional separations and indeed this technique may well be more suited to
      forensic and/or population investigations than the much more laborious and time
      consuming two-dimensional techniques.

PMID- 7737085
TI  - Characterisation of Haemophilus influenzae proteins by two-dimensional gel
      electrophoresis.
AB  - The proteins of nontypable and type b Haemophilus influenzae isolates were
      characterised using two-dimensional polyacrylamide gel electrophoresis (2-D
      PAGE). Coomassie Brilliant. Blue R-250 was used for protein detection. Two
      hundred and twenty eight proteins were resolved from whole cell lysates prepared
      from a standard nontypable H. influenzae strain (designated HI-64443) when
      isoelectric focusing was used for the first-dimensional separation of 2-D PAGE.
      When nonequilibrium pH gel electrophoresis (NEPHGE) was used to separate basic
      proteins in the first dimension, 50 proteins were detected for HI-64443; 20 of
      the basic proteins detected were considered to be unique for this separation
      protocol. The apparent molecular weights and isoelectric points were determined
      for 82 of the proteins resolved for HI-64443. The variation of the proteins from
      the standard bacterial strain (HI-64443) was determined for nontypable H.
      influenzae isolates. On the basis of their electrophoretic mobilities, 17.5% of
      the proteins of HI-64443 were shared by four other nontypable H. influenzae
      strains analysed. These data identified both conserved and variable proteins
      among the nontypable H. influenzae isolates analysed. The results obtained
      indicated that 2-D PAGE was able to discriminate nontypable H. influenzae into
      population clones identified by other procedures. The 2-D protein profiles
      obtained for type b H. influenzae strains were similar to those obtained for
      nontypable H. influenzae strains. The extent of the protein variation observed
      between type b and nontypable H. influenzae strain was similar to that observed
      among nontypable strains alone. These data are discussed in relation to the
      application of 2-D PAGE as a tool for studies on bacterial epidemiology and for
      the analysis of the genome structure and gene expression of Haemophilus
      influenzae.

PMID- 7737086
TI  - Gene linkage of two-dimensional polyacrylamide gel electrophoresis resolved
      proteins from isogene families in Saccharomyces cerevisiae by microsequencing of
      in-gel trypsin generated peptides.
AB  - The total cellular extract of proteins from the yeast Saccharomyces cerevisiae
      was resolved by preparative two-dimensional polyacrylamide gel electrophoresis (2
      D PAGE) where 500 micrograms was loaded per gel, and a number of proteins in
      isogene families were selected for microsequencing analysis. Peptides were
      generated from resolved proteins by in-gel trypsin digestion, and fractionated by
      reversed phase-high performance liquid chromatography (RP-HPLC). Subsequent
      sequencing of peptides yielded internal amino acid sequences which unambiguously
      identified the selected proteins spots as gene products from PCD1, ENO1, ENO2,
      ADH1, HXK2, TDH2, TDH3, SSB1 and SSB2. The chromatograms obtained from RP-HPLC of
      related proteins were utilized to distinguish discriminating peptide fractions.
      With this approach two out of four amino acid differences between Ssb1p and Ssb2p
      were allocated. We estimate that by pooling five preparative gels, at least one
      hundred protein spots in the 2-D pattern of S. cerevisiae will be obtained in
      sequencable amounts.

PMID- 7737087
TI  - An informativity index for multilocus DNA fingerprints.
AB  - An informativity index for multilocus DNA fingerprints, r, was developed. It is
      based upon the Shannon information that a paternal DNA fingerprint conveys about
      the offspring phenotype pattern. Both simulation and empirical data reveal that
      the index r is strongly correlated with the mean log likelihood ratio (paternity
      vs. nonpaternity) expected in trio cases of true paternity. Since r can be
      estimated from DNA fingerprints of unrelated individuals in advance, it will
      provide an easy means to assess the potential utility of a given probe/enzyme
      combination in kinship testing.

PMID- 7737088
TI  - Protein concentration by precipitation with pyrogallol red prior to
      electrophoresis.
AB  - The pyrogallol red protein assay (Clinical Chemistry 1986, 32, 1551-1554) is
      based upon formation of a blue protein-dye complex in the presence of molybdate
      under acidic conditions. However, centrifugation of the assay mixture results in
      loss of color yield and precipitation of the protein-dye complex which can be
      recovered and resolubilized to achieve protein concentration prior to sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. The method has been evaluated
      relative to trichloroacetic acid (TCA) precipitation for recovery and
      electrophoresis of commercial protein and peptide molecular weight markers.
      Precipitation with pyrogallol red-molybdate (PRM) gives better and more uniform
      recovery of both proteins and peptides as compared to TCA. The lower limit of PRM
      precipitation is similar to TCA and corresponds to 1 microgram protein per mL
      assay mixture. This is equivalent to 100 microL of 10 micrograms/mL protein using
      the standard protein assay or 1 microgram/mL protein using a modified assay
      incorporating a fivefold concentrate of the dye reagent. Application of the
      method is demonstrated by concentration of urinary proteins. The method is simple
      and economic and useful for conserving trace amounts of precious sample as it
      allows recovery of protein for electrophoresis following protein assay.

PMID- 7737089
TI  - Electrophoretic conditions for high resolution citrus isozymes in polyacrylamide
      gel electrophoresis.
AB  - Electrophoretic conditions including electrode and gel buffers, acrylamide
      concentration, use of stacking gels, voltage, current, and run time were
      investigated in order to produce isozyme bands of high resolution which would
      facilitate densitometric quantification of enzyme activity following
      polyacrylamide gel electrophoresis (PAGE). Electrode buffers which provided
      optimal conditions for gels stained for the isozymes of malate dehydrogenase
      (MDH), 6-phosphogluconate dehydrogenase (6-PGD), phosphoglucose isomerase (PGI),
      and shikimate dehydrogenase (SkDH) were 0.02 M Tris-glycine, pH 8.5, 0.1 M sodium
      borate, pH 6.0, 0.1 M sodium borate, pH 8.7, and 0.07 M sodium borate, pH 7.0,
      respectively. A 0.5 M Tris-HCl, pH 7.5, gel buffer was optimal for gels stained
      for the isozymes of 6-PGD, PGI and SkDH. A 0.5 M Tris-HCl, pH 8.5, gel buffer was
      best for gels stained for MDH. Stacking gels were found to be detrimental to
      enzyme activity and showed no improvement in resolution for any of the enzymes.
      Acrylamide concentration for gels stained for MDH were 8.7%, gels stained for 6
      PGD and PGI were 7.5%, while gels stained for SkDH had an acrylamide
      concentration of 5.0%. Higher concentrations above these levels caused a
      reduction and in some cases loss of band activity, while below this concentration
      there was a decrease in band resolution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737090
TI  - A new method for the detection of proteolytic activity in Pseudomonas lundensis
      after sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
AB  - A new method for the visualization of proteolytic activity in cell culture
      supernatant from Pseudomonas lundensis after sodium dodecyl sulfate (SDS)--gel
      electrophoresis is described. Following conventional electrophoresis, the gel is
      washed in a methanol-containing buffer to facilitate partial removal of SDS.
      After incubation with 0.5% casein the gel is stained for protein with Coomassie
      Brilliant Blue R-250. Bands with proteolytic activity appear as clear areas in
      the gel against a blue-stained background. Molecular weight standards
      electrophoresed in the same gel stain more intensely than the background and
      allow determination of the molecular weights of the proteolytic components. The
      sensitivity of post-electrophoretic reactivation in SDS-gels was determined using
      trypsin as standard. A slight modification of the technique allowed detection of
      proteolytic activity in nondenaturing and in isoelectric focusing gels.

PMID- 7737091
TI  - Surface-charge reversed capillary zone electrophoresis of inorganic and organic
      anions.
AB  - Anions commonly found in biological fluids such as chloride, citrate, phosphate,
      bicarbonate, lactate, aspartate and glutamate, were determined within 60 s by
      means of capillary zone electrophoresis and indirect UV detection using 10 mM of
      chromate, pH 8.0, as both carrier electrolyte and chromophore. The lower mass
      detection limit was 0.5 pmol. In order to avoid a gradual shift of the pH and, in
      consequence, drifting ionic mobilities due to the formation of hydroxyl ions at
      the cathode, 1 mM of 5,5-diethylbarbiturate was added to the background
      electrolyte. Moreover, fused silica capillaries were coated with a 0.0003%
      solution of hexadimethrine bromide for two minutes between runs to reverse
      electroendosmotic flow which otherwise would counteract the electrophoretic
      migration of the anions and, hence, increase time of analysis. It is concluded
      that charge-reversed capillary zone electrophoresis in concert with indirect UV
      detection is superior to ion chromatography and conductivity detection in the
      determination of inorganic and organic anions in biological fluids both with
      regard to selectivity, sensitivity and speed of analysis.

PMID- 7737092
TI  - Effect of pH and sodium dodecyl sulfate concentration on the analytical window in
      the direct-injection analysis of plasma samples by capillary electrophoresis.
AB  - Plasma samples can be analyzed with direct injection onto a capillary
      electrophoresis system if interactions between the plasma proteins and capillary
      walls are minimized. This can be achieved using micellar electrokinetic capillary
      chromatography with a surfactant such as sodium dodecyl sulfate. The surfactant
      complexes with the proteins, giving them a net negative charge, and thus causes
      them to be repelled from the negatively-charged fused-silica capillary walls.
      Migrating as anions, the complexed proteins appear late in the electropherogram.
      In such analyses, it is important to manipulate the mobility of the analyte(s) of
      interest such that they migrate in the useful analytical time window before the
      plasma proteins. In this article, a study of the effect of buffer pH and
      surfactant concentration on the width of the migration time window is reported.
      It is shown that at pH 6 the migration time window is wide, but reduced
      electroosmosis can result in inordinately long run times; pH 7 gives an
      acceptable analytical window with acceptable run times over a wide range of
      sodium dodecyl sulfate (SDS) concentrations; pH 8 and higher are most useful when
      higher concentrations of surfactant (> 50 mM SDS) are employed.

PMID- 7737093
TI  - The use of coated and uncoated capillaries for the electrophoretic separation of
      DNA in dilute polymer solutions.
AB  - We show that both uncoated and polyacrylamide-coated capillaries provide
      separation of large DNA restriction fragments (2.0-23.1 kbp) by capillary
      electrophoresis in dilute cellulosic polymer solutions. Uncoated capillaries,
      however, provide significantly better resolution of DNA fragments, particularly
      when ultra-dilute polymer solutions are used. This is because electroosmotic flow
      in uncoated capillaries increases the residence time of DNA in the capillary,
      without significantly contributing to band-broadening. At a given field strength
      and polymer concentration in the buffer, the electrophoretic mobilities of DNA
      restriction fragments in coated capillaries are virtually identical to those
      previously measured in uncoated capillaries. It is concluded that the fused
      silica surface of the capillary does not play a significant role in the mechanism
      of DNA separation by capillary electrophoresis in uncrosslinked polymer
      solutions. Thus, the separation of large DNA which has been observed to occur in
      ultra-dilute polymer solutions arises primarily from entanglement interactions
      between the cellulosic polymers and DNA restriction fragments which occur within
      the bulk of the polymer solution.

PMID- 7737094
TI  - Diffusion, Joule heating, and band broadening in capillary gel electrophoresis of
      DNA.
AB  - We calculated the longitudinal and transverse diffusion coefficients for a DNA
      molecule undergoing gel electrophoresis in the limit where it is reptating
      through a dense polymer matrix. Our results indicate that both diffusion
      coefficients increase with the electric field intensity. The transverse and
      longitudinal diffusion coefficients are roughly equal for regular field
      intensities, but the former dominates for the high field intensities normally
      used for capillary gel electrophoresis (CE). This has important implications for
      the optimization of CE. Our results clearly show that the naive use of the zero
      field diffusion constant, the Einstein relation or the longitudinal diffusion
      constant when calculating the contribution of the parabolic temperature profile
      to band broadening may lead to large overestimates under typical CE conditions.
      Finally, we show that the field-dependent diffusion coefficients may be
      responsible for the existence of an optimal field intensity for CE, even if Joule
      heating is neglected.

PMID- 7737095
TI  - Single-strand conformation polymorphism analysis by perpendicular temperature
      gradient gel electrophoresis.
AB  - Using a newly developed temperature-gradient gel electrophoresis apparatus,
      mutations in the K-ras oncogene and p53 tumor suppressor gene were analyzed for
      single-strand conformation polymorphism (SSCP). The mobilities of single-stranded
      DNAs, carrying various mutations, change--depending on the gel temperature during
      electrophoresis. Therefore, temperature-gradient single-strand conformation
      polymorphism (TG-SSCP) analysis can provide useful information concerning the
      optimum temperature for SSCP and may also be used to screen for various mutations
      or polymorphisms in a single electrophoretic run.

PMID- 7737096
TI  - Sodium chloride in separation medium enhances cell compatibility of free flow
      electrophoresis.
AB  - Free flow electrophoresis of cell suspensions in buffers containing sodium
      chloride was investigated using a modified procedure and the new apparatus
      Octopus PZE. The major methodical innovations are upward fluid flow, margin
      buffers flowing through the electrophoresis chamber at both sides of a central
      cell suspension buffer, adjacent to the electrode membranes, and a sample
      injection device which focuses the cells hydrodynamically to the middle of the
      chamber thickness. Mononuclear leukocytes, suspended in a buffer containing 35 mM
      NaCl, could be fractionated with the same accuracy as by conventional free flow
      electrophoresis, operated with a single NaCl-free chamber buffer. However,
      testing the vitality of separated cells with the help of the calcium indicator
      FURA2-AM clearly demonstrated the biological importance of the presence of a
      minimum amount of sodium chloride during cell electrophoresis. Only if at least
      35 mM NaCl were present could an undisturbed cytosolic Ca2+ metabolism be
      maintained for the time of a free flow electrophoresis cell separation
      experiment.

PMID- 7737097
TI  - Preparative reflux electrophoresis.
AB  - As part of the method for large-scale preparative electrophoresis across
      membranes of controlled porosity, we show that successive amounts of the leading
      component of a mixture migrating across a thin membrane can be collected by
      'reflux electrophoresis'. This consists of a series of cycles, in each of which
      the forward phase is stopped before the trailing components can emerge, the
      leading fraction is collected and the membrane cleared by reversing the current
      before commencing the next cycle. The reflux principle is demonstrated by
      separations based on size or on charge differences of protein molecules.

PMID- 7737098
TI  - Validation and adjustment of the mathematical prediction model for human rectal
      temperature responses to outdoor environmental conditions.
AB  - Models to predict rectal temperature (Tre) have been based on indoor laboratory
      studies. The present study was conducted to validate and adjust a previously
      suggested model for outdoor environmental conditions. Four groups of young male
      volunteers were exposed to three different climatic conditions (30 degrees C, 65%
      rh; 31 degrees C, 41% rh; 40 degrees C, 20% rh). They were tested both in shaded
      and open field areas (radiation: 80 and 900 W.m-2, respectively) at different
      work loads (100, 300 and 450 watt). Exercise consisted of two bouts of 10 minutes
      rest and 50 minutes walking on a treadmill, at a constant speed (1.4 m.s-1) and
      different grades. The subjects were tested wearing cotton fatigues and protective
      garments. Their Tre and heart rate were monitored every 5 min and skin
      temperature every 15 min, oxygen uptake was measured towards the end of each bout
      of exercise; concomitantly, ambient temperature, relative humidity and solar load
      were monitored. We concluded that: (a) the corrected model to predict rectal
      temperature overestimates the actual measurements when applied outdoors; (b)
      radiative and convective heat exchanges should be considered separately when
      using the model outdoors; (c) radiative heat exchange should also be considered
      separately for short-wave radiation (solar radiation) and long-wave emission from
      the body to the atmosphere. Finally, an adjusted model to be used outdoors was
      suggested.

PMID- 7737100
TI  - Reproducibility of body temperature response to standardized test conditions when
      assessing clothing.
AB  - The traditional use of core temperature to assess the thermal effects of clothing
      has recently been questioned. The purpose of this study was to assess the
      reproducibility of body temperature in five subjects (mean age, 22.6 +/- 1.5
      years) wearing either athletic clothing or a chemical protective overgarment
      while exercising at 20 degrees C and at 40 degrees C. The exercise was preceded
      by a 1 h adaptation period in a controlled environmental chamber. Results
      indicated that mean group change in rectal temperature (delta Tr) appeared to be
      reproducible for both garment ensembles at 20 degrees C but not at 40 degrees C.
      For mean change in oesophageal temperature (delta T(oes)) at 20 degrees C,
      reproducibility was obtained for the overgarment but not for the athletic
      garment; at 40 degrees C, mean delta T(oes) appeared to be reproducible with both
      garments. However, when individual responses were examined, there was little
      reproducibility for either delta Tr or delta T(oes). In addition, these
      measurements failed to show differences in the types of clothing worn. It was
      concluded that the use of core temperature to assess heat stress imposed by
      wearing clothing during exercise may lead to erroneous conclusions.

PMID- 7737099
TI  - Time course changes in plasma creatine kinase over four days of repetitive manual
      work.
AB  - Time course changes in plasma creatine kinase activity during repetitive physical
      work were studied. Study groups consisted of a control group who performed
      sedentary administrative work and an experimental group who performed repetitive
      physical work in a biscuit factory. Venous blood samples were collected on a
      Monday prior to work and following work on Monday, Tuesday, Wednesday and
      Thursday and assayed for plasma creatine kinase. A rise in plasma creatine kinase
      was observed over the four working days and this rise was significantly greater
      for the experimental group. Despite this rise, creatine kinase values remained
      within acceptable limits for both groups. These results suggest that mild,
      repetitive physical work provides sufficient stimulus for creatine kinase release
      from skeletal muscle. The mechanism underlying the release of creatine kinase
      cannot be determined from the present study, but it is unlikely that muscle
      damage was the cause. It is proposed that increased plasma creatine kinase
      following mild occupational work may be related to increased rates of muscle
      turnover, stimulated by muscle use, and not be indicative of pathological
      processes associated with muscular strain and fatigue.

PMID- 7737101
TI  - Laboratory work with automatic pipettes: a study on how pipetting affects the
      thumb.
AB  - The aim of this study was to assess the strain that is exerted on the thumb when
      working with automatic pipettes. The study consisted of three parts: a survey
      concerning stress-related symptoms in general and in the thumb in particular, a
      study of the working conditions in the laboratory with the help of a video-film,
      and a power test. In the survey the Nordic Council of Ministers' questionnaire
      and a newly developed questionnaire about the thumb were used. A usual and
      frequently carried out analysis that included several different methods of
      pipetting was filmed on video. The power test measured two things, the power that
      is necessary to press down the button of the pipette into different positions and
      the maximal strength when performing a movement in the same direction. It was
      shown that the strain on the thumb for a woman with weak muscular structures is
      unacceptably high. The symptoms increase with the amount of time spent with
      pipetting and with age. In addition, pipetting is done in a position where the
      thumb is not stable but nevertheless has to work to stabilize the grip around the
      pipette and to press down the button of the pipette. Therefore the muscles have
      to work both as mobilizing and stabilizing structures. It is concluded,
      therefore, that some form of automation ought to be taken into consideration if
      the amount of pipetting work tends to increase. The pipettes should be
      constructed with as little button resistance as possible and the handle should be
      designed to fit different hand sizes.

PMID- 7737102
TI  - Effects of posture, weight and frequency on trunk muscular activity and fatigue
      during repetitive lifting tasks.
AB  - We examined the effects of posture, weight and frequency on trunk muscular
      activity and fatigue during repetitive dynamic lifting. Electromyographic (EMG)
      signals from eight primary trunk muscles were collected during 120 min for four
      different task conditions. The patterns of muscle recruitment and the levels of
      relative activation were analysed using the normalized EMG data. Median power
      frequency (MPF) shift patterns were analysed to examine muscular fatigue. The
      muscles in the dorsal part of the trunk were activated at the symmetric posture,
      while the muscles on the contralateral side to the workload were more strongly
      activated at the asymmetric posture. Decreasing trends of MPFs were found in some
      active muscles, and they were more pronounced for the asymmetric posture than for
      the symmetric posture. It was also seen that the muscles became fatigued faster
      for the light load-high frequency task than for the heavy load-low frequency
      task.

PMID- 7737103
TI  - Mental effects of caffeine in fatigued and non-fatigued female and male subjects.
AB  - In experiment 1 eight male and eight female subjects were randomly assigned to
      either a caffeine or a placebo condition. Caffeine (150 mg) was given at midnight
      and at 4 a.m. Oral temperature, subjective ratings of fatigue and mood, and
      performance in two cognitive tasks (an auditive attention task and a visual
      coding task) were assessed. Subjective 'drowsiness' and 'tiredness' increased
      significantly more in subjects given placebo than in subjects given caffeine
      treatment. The effects of drug treatment in performance and temperature were non
      significant. However, the temperature of female subjects increased between
      midnight and 4 a.m. and the temperature of male subjects decreased during the
      same period of time. On the other hand, at 5 a.m. female subjects rated
      themselves as more sleepy, tired and 'disorganized' than the male subjects. In
      experiment 2 nine female and nine male subjects were assigned randomly to either
      placebo or caffeine treatment. Caffeine (200 mg) was given at 5 a.m. Oral
      temperature, subjective ratings of fatigue and mood, and level of performance in
      three cognitive tasks (the same as above plus Raven's progressive matrices) were
      assessed. Moreover, the subjects rated the effort of performing each task. The
      effects of drug treatment in level of performance were non-significant. However,
      the subjective effort of performing the auditive attention task increased
      significantly in subjects given placebo treatment, suggesting a compensatory
      arousal mechanism (Broadbent 1971). The effect of gender on temperature was non
      significant. There was a significant interaction between gender and treatment in
      respect of subjective effort of performing the matrices task. In men caffeine
      decreased subjective effort and in women subjective effort was increased by
      caffeine. Experiment 3 was set up to investigate the hypothesis that negative
      effects of caffeine in women, observed in experiment 2, were due to over-optimal
      ('vigilance-related') arousal for the visual coding and matrices tasks. Ten
      female and eight male non-sleep deprived subjects were given 200 mg caffeine or
      placebos at 3 p.m. and tested at 4 p.m. Experiment 3 was not found to support the
      over-optimal 'vigilance-related-arousal' hypothesis. Effects of caffeine in
      performance and effort were non-significant in experiment 3. Combining data from
      experiments 2 and 3 gave a significant three-way interaction between caffeine,
      time for experiment and rule complexity in the visual coding task. When there was
      a complex rule, caffeine was found to have a positive effect in experiment 3 and
      a negative effect in experiment 2.

PMID- 7737104
TI  - Repetitive work and the monitoring methods of operators in various production
      situations during day- and night-shifts.
AB  - The purpose of this research is to determine to what extent operators carrying
      out repetitive machine-monitoring and feeding work can adapt their monitoring
      methods to the different production situations that they encounter, but also to
      the internal variations in their bodies during a 24-hour period. The activities
      of four log debarker operators were studied in a sawmill operating during the day
      and during the night (7 a.m. to 5 p.m. and 7 p.m. to 5 a.m.). The glance axis
      direction was observed in three more or less conflictual production situations
      (total 16 shifts). The technical and time constraints leave the operators very
      little margin of manoeuvre, and in normal production situations very little
      difference is found in the monitoring methods within one shift and between the
      two shifts. However, changes are observed between the day and night shifts if the
      monitoring methods are compared during production situations that the operators
      find more difficult to manage. These results are not consistent with a decrease
      in activities. In fact, during the night, these operators use their capabilities
      to an even greater extent to monitor a more conflictual situation more
      thoroughly. This result can be explained by the changes in people's memory during
      the night, and by the lower threshold at which an operator decides that a
      situation is critical at night as compared to the daytime.

PMID- 7737105
TI  - The impact of activity level on sweat accumulation and thermal comfort using
      different underwear.
AB  - The purpose of this study was to investigate the significance of work level and
      sweat production for the total amount accumulated and the location of the sweat
      in a three-layer ensemble as a function of material and textile construction.
      Furthermore, it was also an aim to investigate how this influenced
      thermoregulatory responses and thermal comfort during work and during a rest
      period. Long-legged/long-sleeved underwear manufactured from two different 100%
      fibre-type materials, polypropylene and wool, was tested as part of a three-layer
      clothing system. The underwear manufactured from 100% polypropylene was tested in
      two different knit constructions, a 1-by-1 rib knit and a fishnet structure, and
      the woollen underwear in a 1-by-1 rib knit construction. The test was performed
      on eight male subjects (Ta = 10 degrees C, RH = 85%, Va < 0.1 m/s), and comprised
      a twice-repeated bout of 40-min cycle exercise followed by 20 min rest. Each
      subject conducted two tests with the work level approximating 30% VO2 max and 40%
      VO2 max, respectively. Skin temperatures, rectal temperature, weight loss and
      humidity near the skin were recorded during the test. Total changes in body and
      clothing weight were measured separately. Furthermore, subjective ratings on
      thermal comfort and on sensation of temperature and humidity were collected. The
      results demonstrated that high heat and sweat production during work periods,
      leading to increased sweat accumulation, will give higher thermal discomfort
      ratings for rest periods as well as for work periods compared to intermittent
      work with lower work intensities. Distribution of accumulated sweat in the
      clothing ensemble after heavy sweating is dependent on the fibre type in the
      underwear. Further, it can be concluded that underwear construction clearly has
      an influence on the evaporation rate in a three-layer ensemble during work at a
      high activity level.

PMID- 7737106
TI  - Cross-sectional study of risk factors for symptoms in the neck and shoulder area.
AB  - This study was performed in order to evaluate how individual characteristics, as
      well as ergonomic, organizational and psychosocial factors in the work situation
      are associated with early symptoms in the neck and shoulder area. Nine hundred
      randomly drawn subjects of the working population in a semi-rural community in
      Sweden were mailed a questionnaire comprising the Nordic questionnaire on
      musculoskeletal symptoms, questions on ergonomic, organizational and psychosocial
      work conditions, life style factors, and background factors. The total response
      rate was 73% (n = 637). Questions on ergonomic work conditions and on
      organizational and psychosocial work conditions provided the measures of
      exposure. Prevalence ratios (PR) were calculated for symptoms in the neck and
      shoulder area as reported by 303 subjects. Significant determinants for early
      symptoms were being a female and being an immigrant, as were repetitive movements
      demanding precision. High work pace, low work content and work role ambiguity
      were significant organizational risk factors while life style characteristics did
      not appear as risk factors. The results suggest that symptoms are signals not
      only of ergonomic deficiencies in the work situation, but in particular of work
      organizational conditions. Special attention should be given to the work
      conditions of women and immigrants in preventive interventions.

PMID- 7737107
TI  - Validation and adjustment of the mathematical prediction model for human sweat
      rate responses to outdoor environmental conditions.
AB  - Under outdoor conditions this model was over estimating sweat loss response in
      shaded (low solar radiation) environments, and underestimating the response when
      solar radiation was high (open field areas). The present study was conducted in
      order to adjust the model to be applicable under outdoor environmental
      conditions. Four groups of fit acclimated subjects participated in the study.
      They were exposed to three climatic conditions (30 degrees, 65% rh; 31 degrees C,
      40% rh; and 40 degrees C, 20% rh) and three levels of metabolic rate (100, 300
      and 450 W) in shaded and sunny areas while wearing shorts, cotton fatigues (BDUs)
      or protective garments. The original predictive equation for sweat loss was
      adjusted for the outdoor conditions by evaluating separately the radiative heat
      exchange, short-wave absorption in the body and long-wave emission from the body
      to the atmosphere and integrating them in the required evaporation component
      (Ereq) of the model, as follows: Hr = 1.5SL0.6/I(T) (watt) H1 = 0.047Me.th/I(T)
      (watt), where SL is solar radiation (W.m-2), Me.th is the Stephan Boltzman
      constant, and I(T) is the effective clothing insulation coefficient. This
      adjustment revealed a high correlation between the measured and expected values
      of sweat loss (r = 0.99, p < 0.0001).

PMID- 7737108
TI  - Effects of repeated exposures to severely cold environments on thermal responses
      of humans.
AB  - This study was conducted to investigate the effects of different exposure rates
      on thermal responses with the total cold exposure time the same under each of the
      conditions. After resting in a warm room (25 degrees C) for 10 minutes, six male
      students wearing standard cold protective clothing entered an adjoining cold room
      (-25 degrees C). Each 5-, 10- and 20-minute cold exposure was repeated 12, 6 and
      3 times, respectively. Each cold exposure was followed by a similar duration of
      rest at 25 degrees C. Total cold exposure time was the same under the three
      conditions. Rectal temperature, skin temperatures, blood pressure, 17
      hydroxycoyticoids (OHCS), counting task and subjective responses were measured.
      At the end of the cold exposure skin temperatures in the shorter exposures were
      higher than those in the other conditions, except on the foot. Discomfort due to
      cold was less in the shorter exposures and manifestation of discomfort was
      delayed. However, there were no differences among the three conditions in the
      fall of rectal temperature and urinary excretion of 17-OHCS, which are good
      indices of cold stress. Moreover, increase in blood pressure and decrease in
      counting task due to cold were not different among the three conditions. Even
      though the cold exposure time for each stay was short, when cold exposures were
      repeated frequently, cold stress of the whole body and decrease in manual task
      performance were the same as in the longer cold exposure.

PMID- 7737109
TI  - Can back supports relieve the load on the lumbar spine for employees engaged in
      industrial operations?
AB  - In recent years, there has been an increased use of back supports in US industry
      to reduce the frequency and concomitant costs of lower-back disorders. The
      obvious question is, 'Can back supports relieve the load on the lumbar spine for
      employees engaged in industrial operations?'. This paper is directed towards
      answering this question because there have been mixed conclusions in the
      literature reporting on the efficacy of back supports. The literature concerning
      the biomechanical, physiological and psychophysical effects of back supports on
      the human spine has been reviewed as well as the use of back supports to control
      injury in the workplace. A critical assessment of the findings reported by
      various investigators has been made together with a discussion of the mechanisms
      used by the trunk muscles to provide extrinsic stability to the spine. It is
      hypothesized that the extrinsic stability of the spine is manifested through more
      than one mechanism. These mechanisms may act simultaneously or sequentially to
      stabilize the trunk. Finally, the ergonomics of back supports as a corporate
      policy are discussed.

PMID- 7737110
TI  - The proline-rich focal adhesion and microfilament protein VASP is a ligand for
      profilins.
AB  - Profilins are small proteins that form complexes with G-actin and
      phosphoinositides and are therefore considered to link the microfilament system
      to signal transduction pathways. In addition, they bind to poly-L-proline, but
      the biological significance of this interaction is not yet known. The recent
      molecular cloning of the vasodilator-stimulated phosphoprotein (VASP), an
      established in vivo substrate of cAMP- and cGMP-dependent protein kinases,
      revealed the presence of a proline-rich domain which prompted us to investigate a
      possible interaction with profilins. VASP is a microfilament and focal adhesion
      associated protein which is also concentrated in highly dynamic regions of the
      cell cortex. Here, we demonstrate that VASP is a natural proline-rich profilin
      ligand. Human platelet VASP bound directly to purified profilins from human
      platelets, calf thymus and birch pollen. Moreover, VASP and a novel protein were
      specifically extracted from total cell lysates by profilin affinity
      chromatography and subsequently eluted either with poly-L-proline or a peptide
      corresponding to a proline-rich VASP motif. Finally, the subcellular
      distributions of VASP and profilin suggest that both proteins also interact
      within living cells. Our data support the hypothesis that profilin and VASP act
      in concert to convey signal transduction to actin filament formation.

PMID- 7737111
TI  - Mice lacking glial fibrillary acidic protein display astrocytes devoid of
      intermediate filaments but develop and reproduce normally.
AB  - Glial fibrillary acidic protein (GFAP) is the main component of the intermediate
      filaments in cells of astroglial lineage, including astrocytes in the CNS,
      nonmyelin forming Schwann cells and enteric glia. To address the function of GFAP
      in vivo, we have disrupted the GFAP gene in mice via targeted mutation in
      embryonic stem cells. Mice lacking GFAP developed normally, reached adulthood and
      reproduced. We did not find any abnormalities in the histological architecture of
      the CNS, in their behavior, motility, memory, blood-brain barrier function,
      myenteric plexi histology or intestinal peristaltic movement. Comparisons between
      GFAP and S-100 immunohistochemical staining patterns in the hippocampus of wild
      type and mutant mice suggested a normal abundance of astrocytes in GFAP-negative
      mice, however, in contrast to wild-types, GFAP-negative astrocytes of the
      hippocampus and in the white matter of the spinal cord were completely lacking
      intermediate filaments. This shows that the loss of GFAP intermediate filaments
      is not compensated for by the up-regulation of other intermediate filament
      proteins, such as vimentin. The GFAP-negative mice displayed post-traumatic
      reactive gliosis, which suggests that GFAP up-regulation, a hallmark of reactive
      gliosis, is not an obligatory requirement for this process.

PMID- 7737112
TI  - Chemical reconstitution of a chloride pump inactivated by a single point
      mutation.
AB  - The arginine residue R108 plays an essential role in the transport mechanism of
      the light-driven anion pump halorhodopsin (HR) as demonstrated by complete
      inactivation of chloride transport in mutant HR-R108Q. In the presence of
      substrate anions, guanidinium ions bind to the mutant protein with affinities in
      the mM range, thereby restoring transport activity and photochemical properties
      of wild type. One guanidinium ion and one anion are bound per molecule of HR
      R108Q. For HR wild type, HR-R108Q-guanidinium and HR-R108K, differences in
      transport activity and anion selectivity are found which may be explained by
      effects of anion solvation. The agreement between light-induced FTIR difference
      spectra of HR wild type and HR-R108Q-guanidinium demonstrates that no structural
      changes occur in the reconstituted mutant and that the photoreactions of wild
      type and reconstituted mutant are identical. Furthermore, an IR absorbance band
      of the guanidino group of R108 can be identified at 1695/1688 cm-1. In HR-R108Q,
      a guanidinium ion binding close to the mutated residue is proposed to mimick the
      role of the R108 side chain as the anion uptake site. Thus the wild type reaction
      mechanism is reconstituted.

PMID- 7737113
TI  - Potassium-inhibited processing of IL-1 beta in human monocytes.
AB  - Agents that deplete cells of K+ without grossly disrupting the plasma membrane
      were found to stimulate the cleavage of pro-interleukin (IL)-1 beta to mature IL
      1 beta. Agents examined in this study included staphylococcal alpha-toxin and
      gramicidin, both of which selectively permeabilize plasma membranes for
      monovalent ions, the ionophores nigericin and valinomycin, and the Na+/K+ ATPase
      inhibitor ouabain. K+ depletion by brief hypotonic shock also triggered
      processing of pro-IL-1 beta. The central role of K+ depletion for inducing IL-1
      beta maturation was demonstrated in cells permeabilized with alpha-toxin:
      processing of pro-IL-1 beta was totally blocked when cells were suspended in
      medium that contained high K+, but could be induced by replacing extracellular K+
      with Na+, choline+ or sucrose. To test whether K+ flux might also be important in
      physiological situations, monocytes were stimulated with lipopolysaccharide (LPS)
      for 1-2 h to trigger pro-IL-1 beta synthesis, and transferred to K(+)-rich
      medium. This maneuver totally suppressed IL-1 beta maturation. Even after 16 h,
      however, removal of K+ from the medium resulted in rapid processing and export of
      IL-1 beta. Ongoing export of mature IL-1 beta from cells stimulated with LPS for
      2-6 h could also be arrested by transfer to K(+)-rich medium. Moreover, a
      combination of two K+ channel blockers inhibited processing of IL-1 beta in LPS
      stimulated monocytes. We hypothesize that K+ movement and local K+ concentrations
      directly or indirectly influence the action of interleukin-1 beta-converting
      enzyme (ICE) and, possibly, of related intracellular proteases.

PMID- 7737114
TI  - NK-lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and
      cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and
      antitumour activity.
AB  - A 78 residue antimicrobial, basic peptide, NK-lysin, with three intrachain
      disulfide bonds was purified from pig small intestine and characterized. A
      corresponding clone was isolated from a porcine bone marrow cDNA library. The 780
      bp DNA sequence had a reading frame of 129 amino acids which corresponded to NK
      lysin. The clone was used to show that stimulation with human interleukin-2
      induced synthesis of NK-lysin-specific mRNA in a lymphocyte fraction enriched for
      T and NK cells. Lower levels of mRNA were detected in tissues known to contain T
      and NK cells, such as small intestine, spleen and colon. Interleukin-2 also
      induced both proliferation of the lymphocyte fraction and cytolytic function in
      these cells. Immunostaining showed that NK-lysin was present in cells positive
      for CD8, CD2 and CD4. NK-lysin showed high anti-bacterial activity against
      Escherichia coli and Bacillus megaterium and moderate activity against
      Acinetobacter calcoaceticus and Streptococcus pyogenes. The peptide showed a
      marked lytic activity against an NK-sensitive mouse tumour cell line, YAC-1, but
      it did not lyse red blood cells. The amino acid sequence of NK-lysin exhibits 33%
      identity with a putative human preproprotein, NKG5, of unknown function but
      derived from a cDNA clone of activated NK cells. We suggest that NK-lysin is a
      new effector molecule of cytotoxic T and NK cells.

PMID- 7737115
TI  - Cloning of a cDNA for lamina-associated polypeptide 2 (LAP2) and identification
      of regions that specify targeting to the nuclear envelope.
AB  - Lamina-associated polypeptide 2 (LAP2) is an integral membrane protein of the
      inner nuclear membrane, which binds directly to both lamin B1 and chromosomes in
      a mitotic phosphorylation-regulated manner. The biochemical and physiological
      properties of LAP2 suggest an important role in nuclear envelope re-assembly at
      the end of mitosis and/or anchoring of the nuclear lamina and interphase
      chromosomes to the nuclear envelope. We describe the cDNA cloning of LAP2 and
      characterization of its membrane topology and targeting to the nuclear envelope.
      The LAP2 cDNA sequence predicts a protein of 452 amino acids, containing a large
      hydrophilic domain with several potential cdc2 kinase phosphorylation sites and a
      single putative membrane-spanning sequence at residues 410-433. Immunogold
      localization of an LAP2 epitope in isolated nuclear envelopes indicates that the
      large amino-terminal hydrophilic domain (residues 1-409) is exposed to the
      nucleoplasm. By expressing deletion mutants of LAP2 in cultured cells, we have
      identified multiple regions in its nucleoplasmic domain that promote localization
      at the nuclear envelope. These data suggest that targeting of LAP2 to the nuclear
      envelope is mediated by cooperative interactions with multiple binding sites at
      the inner nuclear membrane.

PMID- 7737116
TI  - The yeast spt14 gene is homologous to the human PIG-A gene and is required for
      GPI anchor synthesis.
AB  - The protein encoded by the yeast gene SPT14 shows high sequence similarity to the
      human protein, PIG-A, whose loss of activity is at the origin of the disease
      paroxysmal nocturnal hemoglobinuria. The symptoms of this disease are apparently
      due to a loss of cell surface, glycosylphosphatidylinositol (GPI)-anchored
      proteins. Like PIG-A mutant cells, spt14 mutant cells are defective in GPI
      anchoring due to a defect in the synthesis of GlcNAc-PI, the first step of GPI
      synthesis. The spt14 mutant causes several other abnormalities including
      transcriptional defects and a downregulation of inositolphosphoceramide
      synthesis. We suggest that these defects are indirect results of the loss of GPI
      anchoring.

PMID- 7737117
TI  - Human cyclins B1 and B2 are localized to strikingly different structures: B1 to
      microtubules, B2 primarily to the Golgi apparatus.
AB  - We have raised and characterized antibodies specific for human cyclin B2 and have
      compared the properties of cyclins B1 and B2 in human tissue culture cells.
      Cyclin B1 and B2 levels are very low in G1 phase, increase in S and G2 phases and
      peak at mitosis. Both B-type cyclins associate with p34cdc2; their associated
      kinase activities appear when cells enter mitosis and disappear as the cyclins
      are destroyed in anaphase. However, human cyclins B1 and B2 differ dramatically
      in their subcellular localization. Cyclin B1 co-localizes with microtubules,
      whereas cyclin B2 is primarily associated with the Golgi region. In contrast to
      cyclin B1, cyclin B2 does not relocate to the nucleus at prophase, but becomes
      uniformly distributed throughout the cell. The different subcellular locations of
      human cyclins B1 and B2 implicate them in the reorganization of different aspects
      of the cellular architecture at mitosis and indicate that different mitotic
      cyclin-cyclin-dependent kinase complexes may have distinct roles in the cell
      cycle.

PMID- 7737118
TI  - Yeast spindle pole body duplication gene MPS1 encodes an essential dual
      specificity protein kinase.
AB  - The MPS1 gene has been previously identified by a mutant allele that shows
      defects in spindle pole body (SPB) duplication and cell cycle control. The SPB is
      the centrosome-equivalent organelle in the yeast Saccharomyces cerevisiae, and it
      nucleates all the microtubules in the cell. We report the isolation of the MPS1
      gene, which encodes an essential protein kinase homolog. The MPS1 open reading
      frame has been fused to those that encode the LexA protein or the GST protein and
      both of these constructs function in yeast. The fusion proteins have been
      affinity-purified from yeast extracts and the GST chimeric protein has been found
      to be a phosphoprotein. Both proteins have been used to demonstrate intrinsic in
      vitro protein kinase activity of Mps1p against exogenous substrates and itself
      (autophosphorylation). A mutation predicted to abolish kinase function not only
      eliminates in vitro protein kinase activity, but also behaves like a null
      mutation in vivo, suggesting that kinase activity contributes to the essential
      function of the protein. Phosphoamino acid analysis of substrates phosphorylated
      by Mps1p indicates that this kinase can phosphorylate serine, threonine and
      tyrosine residues, identifying Mps1p as a dual specificity protein kinase.

PMID- 7737120
TI  - Protein H--a bacterial surface protein with affinity for both immunoglobulin and
      fibronectin type III domains.
AB  - Several bacterial species express surface proteins with affinity for the constant
      region (Fc) of immunoglobulin (Ig) G. The biological consequences of the
      interaction with IgG are poorly understood but it has been demonstrated that
      genes encoding different IgG Fc-binding proteins have undergone convergent
      evolution, suggesting that these surface molecules are connected with essential
      microbial functions. One of the molecules, protein H, is present in some strains
      of Streptococcus pyogenes, the most significant streptococcal species in clinical
      medicine. In contrast to other Ig-binding bacterial proteins tested, protein H
      was found to interact also with the neural cell adhesion molecule (N-CAM), a
      eukaryotic cell surface glycoprotein mediating homo- and heterophilic cell-cell
      interactions. The affinity for the interaction between protein H and N-CAM was
      1.6 x 10(8)/M and the binding site on protein H was mapped to the NH2-terminal 80
      amino acid residues. N-CAM and IgG are both members of the Ig superfamily and
      analogous to N-CAM, IgG binds to the NH2-terminal part of protein H. However, the
      binding sites for the two proteins were found to be separate, an unexpected
      result which was explained by the observation that the fibronectin type III
      (FNIII) domains and not the Ig-like domains of N-CAM are responsible for the
      interaction with protein H. Thus, the binding of N-CAM to protein H was blocked
      with fibronectin but not with IgG. Moreover, apart from fibronectin itself and N
      CAM, fragments of fibronectin and the matrix protein cytotactin/tenascin
      containing FNIII domains also showed affinity for protein H.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7737121
TI  - B-1a, B-1b and B-2 B cells display unique VHDJH repertoires formed at different
      stages of ontogeny and under different selection pressures.
AB  - Analyses of VHDJH rearrangements isolated from murine peritoneal B-1a cells
      (CD5+, IgMhi, B220lo), peritoneal B-1b cells (CD5-, IgMhi, B220lo), and
      conventional splenic B cells provide evidence that a unique repertoire of VH
      regions is displayed by each of these B-cell subsets. The B-1a subset is
      characterized by a low N-region diversity, by a high frequency of sequence
      homologies in the VH-D and D-JH junctions, and by a limited exonuclease nibbling
      of the terminals of the joining gene segments. Through expansion in ageing mice,
      B-1a clones with these properties are favoured. B-1b cells are similar to
      conventional B-2 cells with respect to N-region diversity, but are unique in
      terms of D gene expression. Thus, while most murine pre-B and B cells
      preferentially use DSP and DFL gene segments in a given reading frame (RF1), B-1b
      cells frequently express D genes in another reading frame (RF2). Together, these
      findings provide structural evidence for a model where B-1a, B-1b and B-2 cells
      are produced by separate progenitors that are active at different stages of
      ontogeny.

PMID- 7737119
TI  - Interaction between the autokinase EpsE and EpsL in the cytoplasmic membrane is
      required for extracellular secretion in Vibrio cholerae.
AB  - Vibrio cholerae secretes a number of proteins important for virulence, including
      cholera toxin. This process requires the products of the eps genes which have
      homologues in genera such as Aeromonas, Klebsiella and Pseudomonas and are
      thought to form a membrane-associated multiprotein complex. Here we show that the
      putative nucleotide-binding protein EpsE is associated with and stabilized by the
      cytoplasmic membrane via interaction with EpsL. Analysis of fusion proteins
      between EpsE and the homologous ExeE from Aeromonas hydrophila demonstrates that
      the N-terminus of EpsE contains the EpsL binding domain and determines species
      specificity. An intact Walker A box, commonly found in ATP-binding proteins, is
      required for activity of EpsE in vivo and for autophosphorylation of purified
      EpsE in vitro. These results indicate that both the kinase activity of EpsE as
      well as its ability to interact with the putative cytoplasmic membrane protein
      EpsL are required for translocation of toxin across the outer membrane in Vibrio
      cholerae.

PMID- 7737122
TI  - DF 31, a sperm decondensation factor from Drosophila melanogaster: purification
      and characterization.
AB  - We have purified to homogeneity a Drosophila protein which is able to decondense
      Xenopus sperm chromatin. This protein, which we have called DF 31, is a heat
      stable phosphoprotein which displays a molecular weight of 31 kDa on SDS-PAGE,
      but which has an apparent molecular weight of > 200 kDa on gel filtration. We
      show that DF 31 decondenses sperm DNA by displacement of sperm-specific proteins.
      In addition to its sperm decondensation activity, DF 31 is also able to
      facilitate nucleosome loading on both decondensed sperm DNA and on naked DNA
      template. The reaction as catalysed by DF 31 is quite efficient; however, the
      nucleosomes appear to be loaded randomly onto the DNA, not in regular arrays.
      Although the mechanism by which DF 31 aids nucleosome loading is not yet clear,
      it most probably occurs through binding of DF 31 to core histones.

PMID- 7737123
TI  - Contrasting effects of alpha and beta globin regulatory elements on chromatin
      structure may be related to their different chromosomal environments.
AB  - Expression of the human alpha and beta globin gene clusters is regulated by
      remote sequences, referred to as HS -40 and the beta-locus control region (beta
      LCR) that lie 5-40 kb upstream of the genes they activate. Because of their
      common ancestry, similar organization and coordinate expression it has often been
      assumed that regulation of the globin gene clusters by HS -40 and the beta-LCR
      occurs via similar mechanisms. Using interspecific hybrids containing chromosomes
      with naturally occurring deletions of HS -40 we have shown that, in contrast to
      the beta-LCR, this element exerts no discernible effect on long-range chromatin
      structure and in addition does not influence formation of DNase I hypersensitive
      sites at the alpha globin promoters. These differences in the behaviour of HS -40
      and the beta-LCR may reflect their contrasting influence on gene expression in
      transgenic mice and may result from the differing requirements of these elements
      in their radically different, natural chromosomal environments; the alpha cluster
      lying within a region of constitutively 'open' chromatin and the beta cluster in
      a segment of chromatin which opens in a tissue-specific manner. Differences in
      the hierarchical control of the alpha and beta globin clusters may exemplify more
      general differences in the regulation of eukaryotic genes which lie in similar
      open or closed chromosomal regions.

PMID- 7737124
TI  - Chromatin remodeling by GAGA factor and heat shock factor at the hypersensitive
      Drosophila hsp26 promoter in vitro.
AB  - The chromatin structure at the Drosophila hsp26 promoter in vivo is characterized
      by two DNase I-hypersensitive (DH) sites harboring regulatory elements. Proximal
      and distal DH sites are separated by a positioned nucleosome. To study the
      contribution of transcription factors to the establishment of this specific
      chromatin configuration we assembled nucleosomes on the hsp26 promoter using a
      cell-free reconstitution system derived from fly embryos. Both DH sites were
      readily reconstituted from extract components. They were separated by a
      nucleosome which was less strictly positioned than its in vivo counterpart. The
      interactions of GAGA factor and heat shock factor with their binding sites in
      chromatin occurred in two modes. Their interaction with binding sites in the
      nucleosome-free regions did not require ATP. In the presence of ATP both factors
      interacted also with nucleosomal binding sites, causing nucleosome rearrangements
      and a refinement of nucleosome positions. While chromatin remodeling upon
      transcription factor interaction has previously been interpreted to involve
      nucleosome disruption, the data suggest energy-dependent nucleosome sliding as
      main principle of chromatin reorganization.

PMID- 7737127
TI  - The E12 inhibitory domain prevents homodimer formation and facilitates selective
      heterodimerization with the MyoD family of gene regulatory factors.
AB  - Although the ubiquitous helix-loop-helix (HLH) protein E12 does not homodimerize
      efficiently, the myogenic factor MyoD forms an avid DNA-binding heterodimer with
      E12 through the conserved HLH dimerization domain. However, the mechanism which
      ensures this selective dimerization is not understood at present. In our
      functional studies of various amino acid changes in the E12 HLH domain, we found
      that a single substitution in E12 helix 1 can abolish the effect of the E12
      inhibitory domain and results in the efficient DNA binding of the E12 homodimer.
      Competition experiments revealed that the inhibitory domain, in fact, blocks the
      dimerization of E12 rather than DNA binding. MyoD contains two glutamic residues
      in helix 2 that are required for efficient dimerization with E12. More
      importantly, these residues were not essential for dimerization with E12 mutants
      in which the dimerization inhibitory domain had been relaxed, or for dimerization
      with E47 which does not contain the inhibitory domain owing to the use of an
      alternative exon. The positions of these glutamic residues are conserved among
      the four myogenic factors. Thus, members of the MyoD family of gene regulatory
      proteins can overcome the E12 dimerization inhibitory domain through a mechanism
      involving, in part, the negatively charged amino acid residues in helix 2. This
      result describes a novel mechanism facilitating the selective formation of the
      MyoD(MRF)-E12 heterodimer that enhances dimerization specificity and may apply to
      other members of the E-protein family.

PMID- 7737126
TI  - Constraints on transcriptional activator function contribute to transcriptional
      quiescence during early Xenopus embryogenesis.
AB  - We have examined the cause of transcriptional quiescence prior to the mid
      blastula transition (MBT) in Xenopus laevis. We have found distinct requirements
      for transcription of class II and class III genes. An artificial increase of the
      amount of DNA present within the embryo over that found at the MBT allows
      precocious transcription of tRNA genes, but not of the adenovirus E4 or human
      cytomegalovirus (CMV) promoters. Thus titration of an inhibitor by exogenous DNA
      determines class III but not class II gene activation. We demonstrate that the
      action of the inhibitor depends on the association of core histones with DNA. The
      addition of exogenous TBP, together with an increase in the amount of DNA within
      the embryo, allows significant basal transcription of class II genes prior to the
      MBT, whereas it does not increase transcription of tRNA genes. To examine the
      activation of transcription above basal levels, we used a defined minimal
      promoter containing five Gal4 binding sites and the activator Gal4-VP16.
      Precocious transcriptional activation is directed by Gal4-VP16 prior to the MBT,
      demonstrating that a functional transcriptional machinery exists at this early
      developmental stage. Furthermore, since this activation can occur in the absence
      of exogenous TBP or chromatin titration, a transcription factor that can
      penetrate chromatin is sufficient for recruitment of this machinery to a
      promoter. Our results support the hypothesis that the temporal regulation of
      transcription during early embryogenesis in Xenopus reflects not only a titration
      of inhibitors by DNA, but also a deficiency in the activity of transcriptional
      activators prior to the MBT.

PMID- 7737125
TI  - Hormone induces binding of receptors and transcription factors to a rearranged
      nucleosome on the MMTV promoter in vivo.
AB  - Hormonal induction of the mouse mammary tumour virus (MMTV) promoter is mediated
      by interactions between hormone receptors and other transcription factors bound
      to a complex array of sites. Previous results suggested that access to these
      sites is modulated by their precise organization into a positioned regulatory
      nucleosome. Using genomic footprinting, we show that MMTV promoter DNA is
      rotationally phased in intact cells containing either episomal or chromosomally
      integrated proviral fragments. Prior to induction there is no evidence for
      factors bound to the promoter. Following progesterone induction of cells with
      high levels of receptor, genomic footprinting detects simultaneous protection
      over the binding sites for hormone receptors, NF-I and the octamer binding
      proteins. Glucocorticoid or progestin induction leads to a characteristic
      chromatin remodelling that is independent of ongoing transcription. The centre of
      the regulatory nucleosome becomes more accessible to DNase I and restriction
      enzymes, but the limits of the nucleosome are unchanged and the 145 bp core
      region remains protected against micrococcal nuclease digestion. Thus, the
      nucleosome covering the MMTV promoter is neither removed nor shifted upon hormone
      induction, and all relevant transcription factors bind to the surface of the
      rearranged nucleosome. Since these factors cannot bind simultaneously to free
      DNA, maintainance of the nucleosome may be required for binding of factors to
      contiguous sites.

PMID- 7737128
TI  - Dual DNA binding specificity of a petal epidermis-specific MYB transcription
      factor (MYB.Ph3) from Petunia hybrida.
AB  - The MYB.Ph3 protein recognized two DNA sequences that resemble the two known
      types of MYB DNA binding site: consensus I (MBSI), aaaAaaC(G/C)-GTTA, and
      consensus II (MBSII), aaaAGTTAGTTA. Optimal MBSI was recognized by animal c-MYB
      and not by Am305 from Antirrhinum, whereas MBSII showed the reverse behaviour.
      Different constraints on MYB.Ph3 binding to the two classes of sequences were
      demonstrated. DNA binding studies with mutated MBSI and MBSII and hydroxyl
      radical footprinting analysis, pointed to the N-terminal MYB repeat (R2) as the
      most involved in determining the dual DNA binding specificity of MYB.Ph3 and
      supported the idea that binding to MBSI and MBSII does not involve alternative
      orientations of the two repeats of MYB.Ph3. Minimal promoters containing either
      MBSI and MBSII were activated to the same extent by MYB.Ph3 in yeast, indicating
      that both types of binding site can be functionally equivalent. MYB.Ph3 binding
      sites are present in the promoter of flavonoid biosynthetic genes, such as the
      Petunia chsJ gene, which was transcriptionally activated by MYB.Ph3 in tobacco
      protoplasts. MYB.Ph3 was immunolocalized in the epidermal cell layer of petals,
      where flavonoid biosynthetic genes are actively expressed. This strongly suggests
      a role for MYB.Ph3 in the regulation of flavonoid biosynthesis.

PMID- 7737129
TI  - ATF-2 contains a phosphorylation-dependent transcriptional activation domain.
AB  - The ATF-2 transcription factor can mediate adenovirus E1A-inducible
      transcriptional activation. Deletion analysis has indicated that the N-terminal
      region of ATF-2 is essential for this response. Furthermore, the N-terminus can
      activate transcription in the absence of E1A when fused to a heterologous DNA
      binding domain. However, in the intact protein this activation domain is masked.
      In this report we show that residues in the N-terminus required for activation
      are also required for mediating E1A stimulation. In particular two threonine
      residues at positions 69 and 71 are essential. These residues are phosphorylated
      in vivo and can be efficiently phosphorylated in vitro by the JNK/SAPK subgroup
      of the MAPK family. ATF-2 can bind to a UV-inducible kinase through a region in
      the N-terminus that is distinct from the sites of phosphorylation; this binding
      region is both necessary for phosphorylation by JNK/SAPK in vitro and for
      transcriptional activation in vivo. The activity of the N-terminus is stimulated
      by UV irradiation which stimulates the signalling pathway leading to JNK/SAPK.
      Finally, although ATF-2 binds to the E1A protein, the N-terminal activation
      domain is not required for this interaction. The results show that ATF-2, like
      other members of the ATF/CREB family of DNA binding proteins is regulated by
      specific signalling pathways.

PMID- 7737131
TI  - Sequence-dependent bending propensity of DNA as revealed by DNase I: parameters
      for trinucleotides.
AB  - Structural parameters characterizing the bending propensity of trinucleotides
      were deduced from DNase I digestion data using simple probabilistic models. In
      contrast to dinucleotide-based models of DNA bending and/or bendability, the
      trinucleotide parameters are in good agreement with X-ray crystallographic data
      on bent DNA. This improvement may be due to the fact that the trinucleotide model
      incorporates more sequence context information than do dinucleotide-based
      descriptions.

PMID- 7737130
TI  - ATF-2 is preferentially activated by stress-activated protein kinases to mediate
      c-jun induction in response to genotoxic agents.
AB  - The major regulators of the c-jun promoter are ATF-2 and c-Jun. They act as pre
      bound heterodimers on two 'AP-1-like' sites, and are preferentially addressed by
      different types of extracellular signals. The transactivating potential of ATF-2
      is stimulated to a higher extent than that of c-Jun by a broad group of agents
      causing DNA damage and other types of cellular stress, such as short-wavelength
      UV, or the alkylating compounds N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) or
      methylmethanesulphonate (MMS). In contrast, treatment with the phorbol ester TPA
      preferentially enhances c-Jun-dependent transactivation but does not affect ATF
      2. Accordingly, UV and MMS but not TPA induce c-jun transcription in F9 cells,
      which express ATF-2, but not c-Jun. Stimulation of ATF-2-dependent
      transactivation by genotoxic agents requires the presence of threonines 69 and 71
      located in the N-terminal transactivation domain. These sites are the target of
      p54 and p46 stress-activated protein kinases (SAPKs) which bind to, and
      phosphorylate ATF-2 in vitro. However, p46 and p54 kinase activity is not
      increased by phorbol ester, which strongly suggests that the protein kinase
      phosphorylating c-Jun in response to TPA is distinct from SAPKs and does not act
      on ATF-2. Our data demonstrate that distinct signal transduction pathways
      converge at c-Jun/ATF-2, whereby each subunit is individually addressed by a
      specific class of protein kinases. This allows fine tuned modulation of c-jun
      expression by a large spectrum of extracellular signals.

PMID- 7737132
TI  - A pivotal role for the structure of the Holliday junction in DNA branch
      migration.
AB  - Branch migration of a DNA Holliday junction is a key step in genetic
      recombination that affects the extent of transfer of genetic information between
      homologous DNA sequences. We previously observed that the rate of spontaneous
      branch migration is exceedingly sensitive to metal ions and postulated that the
      structure of the cross-over point might be one critical determinant of the rate
      of branch migration. Other investigators have shown that in the presence of
      divalent metal ions like magnesium, the Holliday junction assumes a folded
      conformation in which base stacking is retained through the cross-over point.
      This base stacking is disrupted in the absence of magnesium. Here we measure the
      rate of branch migration as a function of Mg2+ concentration. The rate of branch
      migration increases dramatically at MgCl2 concentrations below 500 microM, with
      the steepest acceleration occurring between 300 and 100 microM MgCl2. This
      increase in the rate of branch migration coincides with the loss of base stacking
      in the four-way junction over this same interval of magnesium concentration, as
      measured by the susceptibility of junction residues to modification by osmium
      tetroxide and diethyl pyrocarbonate. We conclude that at physiological
      concentrations of intracellular Mg2+, base stacking in the Holliday junction
      constitutes one kinetic barrier to branch migration and that disruption of base
      stacking at the cross-over relieves this constraint.

PMID- 7737134
TI  - Determination of hprt mutant and mutation frequencies and the molecular
      characterization of human derived in vivo T-lymphocyte mutants.
AB  - Using a T-lymphocyte clonal assay, 73 6-thioguanine resistant T-lymphocytes were
      isolated from two blood samples obtained 4 months apart from a 50-year-old male
      subject. Sixty-six of these mutants were characterized at the DNA sequence level
      using cDNA. One particular single base substitution was recovered a total of 23
      times. The majority of T-cell receptors (TCR) of these mutants all share a common
      gamma-TCR rearrangement, and thus likely represent a single mutational event that
      underwent clonal expansion in vivo. Siblings of this clone were recovered in both
      collections. Three other single base substitutions were also recovered more than
      once. In two of the three cases, the mutants were also found to be clonally
      related, while in one case they were not. A number of identical exon loss events
      were also recovered, yet none of these were clonally related. This probably
      reflects the multiple pathways by which these mutations can arise. The TCR data
      was used to correct the observed mutant frequency to produce an estimate of the
      actual mutation frequency. The two mutant frequencies, 18 x 10(-6) and 19 x 10(
      6), obtained from the first and second sampling periods, respectively, can thus
      be corrected to yield true mutation frequency's of 12 x 10(-6) each.

PMID- 7737135
TI  - DNA-damaging effect of cyclophosphamide on human blood cells in vivo and in vitro
      studied with the single-cell gel test (comet assay).
AB  - The single-cell gel (SCG) test was used to study the induction and persistence of
      DNA damage by cyclophosphamide (CP) in human blood cells after treatment in vitro
      and in vivo. S9-mix-activated CP (from 0.1 mM upward) induced DNA effects in a
      concentration-dependent manner in the in-vitro SCG test. Blood cells from various
      donors showed considerable intra- and interindividual variability. Incubation of
      CP-treated blood samples at 37 degrees C caused a rapid decrease in DNA effects,
      but DNA migration was still significantly increased 1 hr after the end of the CP
      treatment. Comparative studies with the in vitro sister chromatid exchange (SCE)
      test were performed that demonstrated that much lower CP concentrations (about
      100 times) were required for a significant induction of SCEs. A group of 11
      patients who suffered from vasculitis/collagen disease and were treated with low
      CP doses (50-200 mg/day) exhibited an elevated level of DNA damage in the SCG
      test with peripheral blood cells, compared with a group of 11 control persons or
      5 patients without chemotherapy. Increases in DNA damage were variable and not
      clearly related to the CP dose. SCE tests could successfully be performed with 5
      out of the 11 CP-treated patients; all showed significantly increased SCE
      frequencies. For six patients no result could be obtained with the SCE test due
      to a failure of lymphocyte proliferation. Three multiple sclerosis patients who
      received high doses of CP were investigated with the SCG test before, during, and
      after the treatment. The results indicate that CP-induced DNA effects that are
      detectable with the SCG test persist in vivo for a period of several days, but
      for less than 2 weeks. The results of our study provide information with regard
      to the use of the SCG test in human monitoring. The advantages and limitations of
      the test are discussed.

PMID- 7737133
TI  - Refinement of the high-resolution physical and genetic map of Rhodobacter
      capsulatus and genome surveys using blots of the cosmid encyclopedia.
AB  - Cosmids from a library containing Rhodobacter capsulatus DNA fragments were
      previously ordered in two contigs: one corresponding to the chromosome and one to
      a 134 kb plasmid. This map contained 40 regions connected only by colony
      hybridization. To confirm the linkage and correct the map, the actual sizes of
      the overlaps were determined by blot-hybridization with Rhodobacter chromosomal
      DNA and by mapping of additional cosmids. Several revisions of the earlier map
      include single cosmid shifts and inversions. One additional gap in a cosmid
      contig was also found, raising the possibility that the chromosome is not a
      contiguous circle. About 2500 additional EcoRI,BamHI and HindIII restriction
      sites were added to the 560 EcoRV sites previously mapped onto the Rhodobacter
      chromosome, increasing the resolution of the physical map to the size of
      individual genes. Twenty-five new markers were located on the genetic map. The 48
      markers now mapped represent nearly 300 genes and ORFs cloned from different
      species of Rhodobacter. The orientation of transcription of the four rrn operons
      was established using 16S rRNA- and 23S rRNA-specific probes and digestion with
      the rare-cutting enzyme, CeuI. Gel blots of 192 cosmids of the miniset of
      R.capsulatus digested with EcoRV were prepared. Such a hybridization template
      represents the whole genome cut into 560 DNA fragments varying in size from 0.4
      to 25 kb. This template was used for high-resolution mapping of single genes,
      analysis of total genomic DNAs from related Rhodobacter strains and
      differentially expressed RNAs.

PMID- 7737136
TI  - Sodium arsenite induces chromosome endoreduplication and inhibits protein
      phosphatase activity in human fibroblasts.
AB  - Arsenic, strongly associated with increased risks of human cancers, is a potent
      clastogen in a variety of mammalian cell systems. The effect of sodium arsenite
      (a trivalent arsenic compound) on chromatid separation was studied in human skin
      fibroblasts (HFW). Human fibroblasts were arrested in S phase by the aid of serum
      starvation and aphidicolin blocking and then these cells were allowed to
      synchronously progress into G2 phase. Treatment of the G2-enriched HFW cells with
      sodium arsenite (0-200 microM) resulted in arrest of cells in the G2 phase,
      interference with mitotic division, inhibition of spindle assembly, and induction
      of chromosome endoreduplication in their second mitosis. Sodium arsenite
      treatment also inhibited the activities of serine/threonine protein phosphatases
      and enhanced phosphorylation levels of a small heat shock protein (HSP27). These
      results suggest that sodium arsenite may mimic okadaic acid to induce chromosome
      endoreduplication through its inhibitory effect on protein phosphatase activity.

PMID- 7737137
TI  - Induction of polyploidy in human lymphocytes in vitro by excess adenine, but not
      by adenosine.
AB  - It is known that high levels of DNA precursors can be both clastogenic and
      mutagenic in cultured cell lines and in vivo. The purpose of the present study
      was to examine at an observational level the cytogenetic effects of adenine and
      adenosine in primary human cell cultures. Human peripheral blood lymphocytes from
      four donors were cultured and treated with a range of concentrations of adenine
      and adenosine. Although no increase in sister chromatid exchange (SCE) frequency
      was observed with either compound, there was a statistically significant, dose
      related increase in the proportion of polyploid cells in cultures treated with
      adenine, but not in those treated with adenosine. Some of the polyploid
      metaphases found after adenine treatment contained diplochromosomes, suggesting
      that endoreduplication might have been involved in polyploid formation in these
      cells. It is concluded that a high level of adenine can cause genetic changes in
      human lymphocytes by interfering with mitosis, perhaps by disturbing the balance
      of DNA precursor pools.

PMID- 7737138
TI  - Interaction of 7H-dibenzo[c,g]carbazole and its organspecific derivatives with
      hepatic mitochondrial and nuclear DNA in the mouse.
AB  - The recent observation of a high level of adducts in mitochondrial DNA (mtDNA) of
      cells exposed to chemical carcinogens aroused new interest in the hypothesis that
      carcinogen-induced damage in mitochondria plays a role in one or more stages of
      carcinogenesis. In order to investigate whether differences in the metabolic
      activation of carcinogens have qualitative and quantitative effects on ml- and
      nuclear DNA (nuDNA) adduct formation, mice were exposed to the potent
      hepatocarcinogenic and sarcomagenic polycyclic hydrocarbon 7H
      dibenzo[c,g]carbazole (DBC) and to three of its derivatives that show large
      differences in enzymatic activation: N-acetyl-DBC (N-AcDBC), which is
      carcinogenic for several tissues; 5,9-dimethyl-DBC (DiMeDBC), which is
      exclusively hepatocarcinogenic; and N-methyl-DBC (N-MeDBC), which is exclusively
      sarcomagenic. Adduct formation and toxic effects were measured over 48 hr. With a
      moderate 5 mumol/kg dose of DBC, the adduct level in liver 24 hr after treatment
      was always higher in nuDNA than in mtDNA; after 48 hr a substantial increase in
      the level of adducts in mtDNA was observed, with a parallel decrease in the level
      in nuDNA. With DiMeDBC, a 4.9-fold increase in mtDNA was seen at 48 hr, whereas,
      at the same dose, the non-hepatocarcinogenic N-MeDBC induced a very small number
      of adducts. In order to obtain a nearly identical level of adducts in nu- and
      mtDNA at 24 hr, the dose of DBC must be three times higher (15 mumol/kg); this
      and higher dose levels had a strong cytotoxic effect in liver cells. Qualitative
      differences in adduct distribution were observed on chromatograms of mtDNA and
      nuDNA, showing that the access to mtDNA is a complex process. Our results confirm
      that mouse liver mtDNA is a major target for DBC and its hepatocarcinogenic
      derivatives. The possible interference of genotoxic alterations in mtDNA with
      carcinogenic mechanisms is discussed.

PMID- 7737139
TI  - Induction of delayed mutations by benzene and ethylene dibromide in Drosophila.
AB  - Two carcinogens, ethylene dibromide and benzene, were used to induce delayed
      (germinal mosaic) sex-linked recessive lethal mutations in spermatozoa and
      spermatids of adult Drosophila males. Significant numbers of delayed mutations
      (in F3) were scored in absence of conventional (in F2) mutations. A large
      proportion of nonlethal F2 cultures carried delayed mutations, so much so that,
      in some cultures, all F2 females were carriers of mutations. The mechanism
      through which single strand damage to treated X chromosomes can result in such
      delayed lethals is discussed. These observations indicate that the delayed
      mutation test should be used for testing the mutagenicity of environmental
      compounds, especially carcinogens, which tested negative in the conventional sex
      linked recessive lethal mutation test. The data will support the relationship
      between mutagenesis and carcinogenesis and, also will further enhance the
      sensitivity of the Drosophila mutation assay.

PMID- 7737140
TI  - Overview of mutation assays in transgenic mice for routine testing.
AB  - There is scientific and regulatory interest in using mutation assays in
      transgenic mice in safety assessments for new chemicals and drugs. Currently
      these assays are in the process of being validated, and protocols for routine
      testing are being defined. Some of the issues and results to date with regard to
      assay validation include reproducibility of the assay results (they are
      qualitatively reproducible), relevance of the test system (the transgene closely
      approximates an endogenous mammalian gene as a mutational target for the limited
      number of compounds tested), and the predictivity of the assay for heritable
      effects (unknown at this time) or carcinogenicity (the assays show good positive
      predictivity for carcinogenicity; the negative predictivity of the assay requires
      further investigation). Definition of appropriate study protocols for routine
      testing requires that applicable statistical methods are available and that the
      experimental parameters that affect the detection of mutations are known.
      Progress made in identifying these parameters is discussed. A proposal is made
      for the custom design of routine safety studies, which is based on the
      anticipated use of each individual test agent. A working group has been formed to
      conduct some of the studies still required for validation of these assays.

PMID- 7737141
TI  - Study design and sample sizes for a lacI transgenic mouse mutation assay.
AB  - Design features that adjust and account for excess variation in a transgenic
      mouse mutation assay based on a lacI target transgene from E. coli are
      considered. These features include proper identification of plate, packaging
      reaction, and animal identifier codes throughout the experimental and analysis
      phases of the study, "blocking" of exposed and unexposed animals when preparing
      and plating multiple packaging reactions from the same genomic DNA sample,
      separating sectored mutant plaques and complete mutant plaques before performing
      any quantitative analyses, and testing for sources of excess variation
      attributable to features of the experimental protocol--such as plate-to-plate
      (within packaging reactions), packaging reaction-to-packaging reaction (within
      animals), and animal-to-animal (within study). Control and ethylnitrosourea
      treated animal data are presented from a fully designed study in the lacI assay.
      The study design incorporates many of these experimental principles. Statistical
      methods to identify excess variability are noted, and the designed study data are
      used to illustrate the types of variability encountered in practice. A standard
      statistical test for two-sample testing is highlighted, from which
      recommendations are made for sample size selection in future studies.

PMID- 7737142
TI  - Statistical design and analysis of mutation studies in transgenic mice.
AB  - We have been working on identifying sources of variability in data from
      transgenic mouse mutation assays in order to develop appropriate statistical
      methods and designs for routine studies. Data from our lab and elsewhere point to
      the presence of significant animal-to-animal variability, which must be taken
      into account in statistical hypothesis tests. Here, the usual Cochran-Armitage
      (CA) test for trend in mutant frequencies, which takes the transgene as the
      experimental unit, and a generalized Cochran-Armitage test (GCA), which takes the
      animal as the experimental unit, are contrasted in computer simulations that help
      to quantify the differences between these statistical tests. The simulations
      report the statistical power of each test to detect treatment group differences,
      and their type I error rates. We find in general that the GCA test performs
      poorly compared to the CA test when it is appropriate to take the transgene as
      the experimental unit, and the study also uses a small number of animals.
      However, the CA test performs poorly in small group-size studies when the animal
      is the appropriate experimental unit. Extensions of the computer simulations
      allow for identification of cost-effective experimental designs. The results
      emphasize that the benefits of using additional animals in these mutation studies
      can be realized without substantial increases in costs. Here we illustrate the
      methods for liver studies in our lab. These methods can be used to derive optimal
      experimental designs for any combination of spontaneous mutant frequency and
      animal-to-animal variability.

PMID- 7737143
TI  - Software package for the management of sequencing projects using lacI transgenic
      animals.
AB  - The bacterial lacI gene has been used for many years as a mutational target for
      the study of the mechanisms of mutation. A wealth of information has been
      collected for many mutagenic treatments and in strains with diverse DNA repair
      backgrounds. Recently this gene has been used in the construction of a transgenic
      mouse, named Big Blue, and a transgenic rat, as well as a rat cell line. The lacI
      gene in these animals and cells can conveniently be recovered and analyzed in
      bacteria. This makes it possible to study mutagenic potential of chemical
      compounds in vivo using a mammal. Tissue, strain, and gender specificity can be
      addressed. In addition, mutations recovered from tumour tissues or from animals
      with specific genetic backgrounds can be analyzed conveniently. The mammalian
      systems can produce large numbers of mutants that require computer assistance to
      manage the samples and the resulting DNA sequence data. Accordingly, a computer
      software system was developed. The system maintains an inventory of bacteriophage
      lambda lacI mutants and allows entry of mutant sequences while performing
      accuracy checks on the data. The software features several options for displaying
      lists of mutants. The system can perform several analyses, including mutant class
      compilations, mutational spectra comparisons, and clonal expansions analysis. An
      extensive database obtained from the bacterial lacI system is included with the
      software and can be analyzed along with mutants derived from transgenic animals.

PMID- 7737144
TI  - Dosing regimens for transgenic mouse mutation assays: the dangers of facing in
      two directions at the same time.

PMID- 7737145
TI  - The major N-linked carbohydrate chains from human urokinase. The occurrence of 4
      O-sulfated, (alpha 2-6)-sialylated or (alpha 1-3)-fucosylated N
      acetylgalactosamine(beta 1-4)-N-acetylglucosamine elements.
AB  - The primary structure of the major N-linked carbohydrate chains attached to
      Asn302 of urinary-type plasminogen activator (urokinase) have been determined.
      Urokinase was completely deglycosylated with peptide-N4-(N-acetyl-beta
      glucosaminyl)asparagine amidase F from Flavobacterium meningosepticum. Released
      oligosaccharides were separated from the remaining protein using gel-permeation
      chromatography on Bio-Gel P-100, and then on Bio-Gel P-6. Fractionation of the
      oligosaccharides was achieved by a combination of FPLC anion-exchange
      chromatography on Mono Q HR 5/5 and amine-adsorption HPLC on LiChrospher 100-NH2.
      Analysis by 1H-NMR spectroscopy demonstrated that the collection of N-glycans
      comprises di-, tri-, and tri'-antennary structures. The glycans contain
      predominantly GalNAc beta 1-4GlcNAc beta instead of Gal beta 1-4GlcNAc beta
      elements. The GalNAc residue is mainly sulfated at O4, or to a lesser extent it
      bears N-acetylneuraminic acid at O6; alternatively the GlcNAc residue can be
      fucosylated at O3. The major component, which accounts for more than 30 mol/100
      mol of the total oligosaccharide pool, consists of an (alpha 1-6)-fucosylated
      diantennary N-linked carbohydrate chain with (SO4-)-4GalNAc beta 1-4GlcNAc beta 1
      2 antennae.

PMID- 7737146
TI  - Potentiation of anticancer-drug cytotoxicity by multidrug-resistance
      chemosensitizers involves alterations in membrane fluidity leading to increased
      membrane permeability.
AB  - We are studying the mechanism underlying chemosensitization of anticancer-drug
      cytotoxicity in wild-type and multidrug-resistant (MDR) mammalian cells. We show
      here that the chemosensitizers, reserpine and verapamil, display a dramatic
      potentiation of taxol, anthracycline and Vinca alkaloids cytotoxicity in P
      glycoprotein-(P-gp)-deficient hamster and human nasopharyngeal carcinoma cells.
      We have therefore utilized this phenomenon to probe for the putative P-gp
      independent component of cytotoxicity chemosensitization. These chemosensitizers
      yielded a marked increase in the accumulation of taxol in parental hamster and
      human carcinoma cells that are devoid of P-gp. These chemosensitizers and non
      ionic detergents brought about a pronounced increase in the accumulation of
      structurally and mechanistically diverse lipophilic chromophores in parental and
      MDR hamster cells. Furthermore, non-toxic concentrations of these non-ionic
      detergents yielded a marked potentiation of taxol cytotoxicity in parental cells.
      These findings were consistent with a chemosensitizer-mediated, P-gp-independent
      increase in membrane permeability. Thus, several aspects of chemosensitizers'
      interaction with lipid bilayers and biomembranes were studied. In this respect,
      like various mild detergents, chemosensitizers induced a dose-dependent leakage
      of carboxyfluorescein encapsulated in liposomes. Like specialized membrane
      fluidizers, various chemosensitizers induced a dose-dependent membrane
      fluidization (and sometimes rigidification) in both liposomes and various wild
      type and MDR animal and human cells, as revealed by diphenylhexatriene
      fluorescence polarization. Furthermore, a favorable correlation was observed
      between the ability of chemosensitizers to permeabilize lipid bilayers and their
      capacity to potentiate anticancer-drug cytotoxicity. Thus, we propose that
      chemosensitizer-mediated changes in the physical properties of biomembranes,
      including altered fluidity and increased permeability, may be important factors
      in achieving potentiation of anticancer-drug cytotoxicity in wild-type and MDR
      mammalian cells. This study offers a basis for the chemosensitizer-mediated
      potentiation of drug toxicity to healthy tissues, thus emphasizing the importance
      of a prior evaluation of the potential untoward toxicity when simultaneously
      using MDR chemosensitizers and cytotoxic agents in the clinic.

PMID- 7737147
TI  - Signal recognition particle (SRP), a ubiquitous initiator of protein
      translocation.
AB  - In higher eukaryotes, most secretory and membrane proteins are synthesised by
      ribosomes which are attached to the membrane of the rough endoplasmic reticulum
      (RER). This allows the proteins to be translocated across that membrane already
      during their synthesis. The ribosomes are directed to the RER membrane by a
      cytoplasmic ribonucleoprotein particle, the signal recognition particle (SRP).
      SRP fulfills its task by virtue of three distinguishable activities: the binding
      of a signal sequence which, being part of the nascent polypeptide to be
      translocated, is exposed on the surface of a translating ribosome; the
      retardation of any further elongation; and the SRP-receptor-mediated binding of
      the complex of ribosome, nascent polypeptide and SRP to the RER membrane which
      results in the detachment of SRP from the signal sequence and the ribosome and
      the insertion of the nascent polypeptide into the membrane. Evidence is
      accumulating that SRP is not restricted to eukaryotes: SRP-related particles and
      SRP-receptor-related molecules are found ubiquitously and may function in protein
      translocation in every living organism. This review focuses on the mammalian SRP.
      A brief discussion of its overall structure is followed by a detailed description
      of the structures of its RNA and protein constituents and the requirements for
      their assembly into the particle. Homologues of SRP components from organisms
      other than mammals are mentioned to emphasize the components' conserved or less
      conserved features. Subsequently, the functions of each of the SRP constituents
      are discussed. This sets the stage for a presentation of a model for the
      mechanism by which SRP cyclically assembles and disassembles with translating
      ribosomes and the RER membrane. It may be expected that similar mechanisms are
      used by SRP homologues in organisms other than mammals. However, the mammalian
      SRP-mediated translocation mechanism may not be conserved in its entirety in
      organisms like Escherichia coli whose SRP lack components required for the
      function of the mammalian SRP. Possible translocation pathways involving the
      rudimentary SRP are discussed in view of the existence of alternative, chaperone
      mediated translocation pathways with which they may intersect. The concluding two
      sections deal with open questions in two areas of SRP research. One formulates
      basic questions regarding the little-investigated biogenesis of SRP. The other
      gives an outlook over the insights into the mechanisms of each of the known
      activities of the SRP that are to be expected in the short and medium-term
      future.

PMID- 7737148
TI  - Homologous nuclear-encoded mitochondrial and cytosolic isoproteins. A review of
      structure, biosynthesis and genes.
AB  - Mitochondrial and cytosolic proteins may be expected to differ in specific traits
      due to their different intracellular location. However, the identification of
      these differences between mitochondrial and cytosolic proteins is complicated by
      the heterogeneity of the two protein groups. These difficulties have been
      overcome by comparing traits of homologous genes, which are derived from a common
      ancestor gene, and their gene products. An earlier report [Hartmann, C.,
      Christen, P. & Jaussi, R. (1991) Nature 352, 762-763] describing a positive net
      charge difference between the mature parts of nuclear-encoded mitochondrial
      proteins and their homologous cytosolic isoproteins, could be corroborated by
      extending the data collection. New data were gathered from computer databases and
      published studies. The average isoelectric points of the mitochondrial and
      cytosolic isoproteins are 7.5 and 6.5, respectively. Depending on the type of
      protein, the observed difference results from differences in the number of basic
      and/or acidic amino acid residues in the isoproteins. Probably both the
      conditions required for mitochondrial protein import and the local conditions
      within the organelle furthered the evolution of basic protein structures. The
      contribution of the mitochondrial targeting peptide to the positive charge of
      precursors of nuclear-encoded mitochondrial proteins is largest when the value of
      the isoelectric point of the mature protein is small. This mutual dependence of
      the charge of the targeting peptide and the mature protein part supports the
      notion that positive charge is essential for mitochondrial protein import.
      Several traits other than electric charge, i.e. codon usage, chromosome location,
      structural organization or regulation of the genes, do not show specific
      differences between the sets of the heterotopic isoproteins. There is no
      preference of gene location for any of the gene sets; only rarely are the genes
      for a mitochondrial and a cytosolic isoprotein located on the same chromosome. A
      variant of the 3' splice-site consensus exists in genes of nuclear-encoded
      mitochondrial proteins. This is most likely a consequence of the evolution of the
      genes in separate lineages before endosymbiosis led to the formation of
      mitochondria. Some of the original mRNA group II intron self-splicing functions
      of the endosymbiont seem to persist in part of the cytosolic splicing machinery
      and apparently require a specific consensus sequence [Juretic, N., Jaussi, R.,
      Mattes, U. & Christen, P. (1987) Nucleic Acids Res.15, 10083-10086].

PMID- 7737149
TI  - The ard1 gene from Streptomyces capreolus encodes a polypeptide of the ABC
      transporters superfamily which confers resistance to the aminonucleoside
      antibiotic A201A.
AB  - A gene (ard1) encoding resistance to the aminonucleoside antibiotic A201A was
      cloned from Streptomyces capreolus NRRL 3817, the producing organism, and
      expressed in Streptomyces lividans. The gene ard1 induced antibiotic resistance
      that was highly specific for A201A. The nucleotide sequence of ard1 contains an
      open reading frame of 1677 bp. Transcription initiation was found to take place
      approximately 86 nucleotides preceding the ATG translation-initiation codon,
      indicating that ard1 is transcribed from its own promoter. The deduced protein
      sequence (Ard1, 558 amino acids) presents two ATP-binding domains with
      significant similarities to those of the ATP-binding cassette transporters (ABC
      transporters) superfamily, including some that confer drug resistance in a
      variety of antibiotic-producing Streptomyces, other Gram-positive bacteria and
      eukaryotic cells. As is probably the case for most of these proteins, the
      mechanism of A201A resistance conferred by Ard1 is an active efflux energized by
      ATP hydrolysis.

PMID- 7737150
TI  - Molecular cloning and DNA sequence analysis of pepL, a leucyl aminopeptidase gene
      from Lactobacillus delbrueckii subsp. lactis DSM7290.
AB  - A genomic library of Lactobacillus delbrueckii subsp. lactis DSM7290 DNA
      fragments from a Sau3A partial digestion in the low-copy-number vector pLG339,
      was used to screen Escherichia coli for the presence of peptidases. Using the
      chromogenic substrate leucine-beta-naphthylamide (Leu-NH-Nap) and E. coli strain
      CM89 lacking the corresponding enzyme activity in an enzymic plate assay, allowed
      the isolation of two peptidase genes; the newly described pepL and the recently
      cloned and sequenced pepN. Clones could be distinguished not only by the
      restriction pattern of isolated plasmids but also by the rate and intensity of
      their colour reaction with Leu-NH-Nap. Three out of five clones were identified
      to express the Lactobacillus pepN gene; the others were shown to express a second
      aminopeptidase gene, designated pepL. This gene, together with 200 bp upstream of
      the proposed AUG initiation codon, was further subcloned and sequenced. The
      corresponding open reading frame of 897 nucleotides is predicted to encode a
      protein of 299 amino acids (34,541 Da). Searching the EMBL database revealed
      similarity to the prolinase of Lactobacillus helveticus (45.8% identity), to the
      iminopeptidases of Lb. delbrueckii subsp. lactis and Lb. delbrueckii subsp.
      bulgaricus (25.5%), and to the Bacillus coagulans prolinase (21.5%). Minor
      similarities were detected for hydrolytic enzymes with serine active sites. The
      product encoded by the pepL gene was functional but could not be visualized on
      Coomassie-blue-stained polyacrylamide gels. High level expression of peptidase L
      in E. coli was achieved by placing the gene under the control of the T7 promoter.

PMID- 7737151
TI  - Diacylglycerol elevations in control platelets are unaccompanied by pleckstrin
      phosphorylation. Implications for the role of diacylglycerol in platelet
      activation.
AB  - Several laboratories have reported that diacylglycerol levels in human platelets
      (approximately 100 pmol/10(9) platelets) increased severalfold in response to 0.5
      1 U/ml thrombin. We report here fluctuations in diacylglycerol mass in control
      platelets, the magnitude of which were 60-90% of that measured in platelets
      treated with 0.2-0.5 U/ml of thrombin. These control platelets were not activated
      by such criteria as absence of aggregation, secretion, phosphatidic acid
      production and phosphorylation of the protein kinase C substrate, pleckstrin.
      Thrombin treatment evoked all of the above responses. Analysis of the
      diacylglycerol molecular species by reverse-phase HPLC of the dimethylated,
      phosphorylated derivatives showed that all of the molecular species that were
      present in control platelets were also present in thrombin-treated platelets.
      Most of the species appeared to fluctuate at random in control platelets with the
      exception of 1-stearoyl-2-arachidonoyl-sn-glycerol which was more or less stable
      and increased severalfold over control values only upon thrombin treatment.
      Furthermore, only this species accumulated as [32P]phosphorylated PtdOH in
      thrombin-treated platelets prelabelled with [32P]Pi. Our findings show that, in
      platelets, elevation of diacylglycerol molecular species other than the 1
      stearoyl-2-arachidonoyl species occurs, but these changes are not necessarily
      linked to activation of protein kinase C as measured by pleckstrin
      phosphorylation which was observed only upon elevation of 1-stearoyl-2
      arachidonoyl-sn-glycerol.

PMID- 7737152
TI  - Phosphatidylinositol hydrolysis and an increase in Ca2+ concentration in the
      signal-transduction process triggered by murine Fc gamma RIII are not required
      for protein kinase C translocation.
AB  - Murine class III receptors for IgG (mFc gamma RIII) are composed of an IgG
      binding alpha chain associated with a gamma subunit dimer. These receptors have
      been shown to trigger the release of serotonin and tumor necrosis factor-alpha
      [Daeron, M., Latour, S., Huckel, C., Bonnerot, C. & Fridman, W. H. (1992)
      Immunobiology 185, 159-174], and are involved in endocytosis and phagocytosis
      [Daeron, M., Malbec, O., Bonnerot, C., Latour, S., Segal, D. M. & Fridman, W. H.
      (1994) J. Immunol. 152, 783-792]. Using a transfection model where the cDNA
      encoding mFc gamma RIII was stably transfected into the rat basophilic leukemia
      cell line RBL-2H3, we found that the functional efficiency of mFc gamma RIII is
      correlated with its ability to increase the intracellular Ca2+ concentration and
      to stimulate inositol phosphate metabolism. The deletion of intracellular
      sequences of the alpha subunit did not alter the ability of mFc gamma RIII to
      trigger the Ca2+ and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]
      response. After substitution of the intracellular domain of mFc gamma RIII for
      that of mFc gamma RIII gamma, but not that of mFc gamma RIII alpha, the chimeric
      receptor was also able to trigger Ca2+ and PtdIns(4.5)P2 responses. In contrast,
      all transfected receptors induced protein kinase C translocation. Furthermore,
      dimerization of the receptor was sufficient for the initiation of this protein
      kinase C translocation while a further crosslinking was necessary for the
      induction of the Ca2+ and PtdIns(4,5)P2 responses. Protein kinase C translocation
      therefore can be dissociated from Ca2+ mobilization, PtdIns(4,5)P2 turnover and
      mast cell secretory responses induced by murine Fc gamma RIII.

PMID- 7737153
TI  - Structural aspects of bile acids involved in the regulation of cholesterol 7
      alpha-hydroxylase and sterol 27-hydroxylase.
AB  - We have recently reported that coordinate down-regulation of cholesterol 7 alpha
      hydroxylase and sterol 27-hydroxylase by bile acids results in suppression of
      bile acid synthesis in cultured rat hepatocytes [Twisk, J., De Wit, E. & Princen,
      H. M. G. (1995) Biochem. J. 305, 505-511]. In the current study, we have assessed
      the effects of a large group of different bile acids, both naturally occurring
      and synthetic, on these two key enzymes, to elucidate structural features which
      render bile acids potent as regulators of bile acid synthesis. Addition of 50
      microM deoxycholate or cholate, two relatively hydrophobic bile acids, to the
      culture medium of hepatocytes resulted in strong suppression of cholesterol 7
      alpha-hydroxylase (suppression of 75%) and 88%, respectively) and sterol 27
      hydroxylase activity (suppression of 76% and 72%, respectively). These effects
      were also reflected in the mRNA levels and the transcriptional activities of the
      two enzymes, showing a parallel suppression of both parameters in response to
      cholate (suppression of 78% and 43% for cholesterol 7 alpha-hydroxylase mRNA and
      transcription, respectively, and suppression of 76% and 42% for sterol 27
      hydroxylase mRNA and transcription, respectively). In contrast, no effects were
      observed with the two hydrophilic bile acids, beta-muricholate and ursocholate.
      Transient expression analysis in cultured rat hepatocytes, using a promoter
      reporter construct containing the proximal part of the cholesterol 7 alpha
      hydroxylase promoter, demonstrated a reduction of transcriptional activity by
      cholate (reduction of 72%), but not by ursocholate. Assessment of the effects of
      27 different bile acids, varying in the number, position and orientation
      (alpha/beta) of hydroxyl groups on the steroid nucleus of the molecule, on
      cholesterol 7 alpha-hydroxylase mRNA showed only a moderate correlation with the
      hydrophobicity index of the bile acid involved (r = 0.61; P < 0.0001). Analysis
      of the three-dimensional structure of a number of these bile acids suggests that
      hydroxyl groups situated in close proximity to each other within the molecule,
      creating a hydrophilic environment, as in the case of cholate, may be a
      prerequisite for a strong inhibitory potency. Deviation from this situation leads
      to a markedly lesser effect on suppression of cholesterol 7 alpha-hydroxylase and
      sterol 27-hydroxylase.

PMID- 7737154
TI  - Actinomycin D stimulates the transcription of rRNA minigenes transfected into
      mouse cells. Implications for the in vivo hypersensitivity of rRNA gene
      transcription.
AB  - The in vivo hypersensitivity of eukaryotic rRNA gene transcription to actinomycin
      D has long been known, but this effect could not be reproduced in model systems
      and its molecular mechanisms remain uncertain. We studied the action of
      actinomycin D using mouse rRNA minigenes (with RNA polymerase I promoter and
      terminator signals), carrying truncated mouse or human rDNA inserts, which are
      faithfully transcribed upon transient transfection into mouse cells. Low
      concentrations (0.01-0.08 micrograms/ml) of actinomycin D caused within 1-2 h a 2
      7-fold stimulation of the transcription of rRNA minigenes which is inversely
      related to the size of the rDNA transcript. With transcripts longer than 3 kb the
      effect was reversed and at 4 kb a practically complete inhibition of the
      formation of full-length transcripts was observed, accompanied, however, by an
      enhanced accumulation of unfinished rDNA transcripts. The dependence of
      actinomycin D action on transcript length was also observed with lacZ gene
      segments of different size inserted into the mouse rRNA minigenes. The
      transcription initiation of endogenous rRNA genes was also stimulated by the low
      doses of actinomycin D as indicated by the enhanced synthesis of unfinished rDNA
      transcripts (spanning mainly the 5' external transcribed spacer), whereas the
      synthesis of full-length transcripts was abolished. Removal of actinomycin D from
      the medium caused within 8-24 h a dramatic increase of the transcription from all
      rRNA minigenes tested. This stimulation was also inversely related to the size of
      the transcripts and varied from twofold to fivefold for the 3-4-kb transcripts to
      about 50-80-fold for the basic minigene transcript (395 nucleotides). The amount
      of endogenous aborted rDNA transcripts was also markedly increased, but the
      synthesis of full-length transcripts was not restored even 24 h after removal of
      the drug. The present results reproduce in a model cellular system the in vivo
      hypersensitivity of rRNA gene transcription to actinomycin D and reveal that the
      major factor involved is the size of the rRNA gene transcript. This effect
      requires only the basic rRNA gene promoter and terminator signals and does not
      depend on the G + C content of the RNA polymerase I transcripts. We suggest that
      at low concentrations, the intercalation of actinomycin D changes the
      conformation of DNA in the promoter region in a manner that stimulates the
      transcription of both endogenous and transfected rRNA genes.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7737155
TI  - DNA interactions of antitumor platinum(IV) complexes.
AB  - Modifications of natural DNA and synthetic double-stranded
      oligodeoxyribonucleotides by cis-diamminedichloro-trans-dihydroxyplatinum(IV)
      (oxoplatin) were studied by means of ELISA, Maxam-Gilbert footprinting
      techniques, HPLC of enzymically digested DNA, and transcription assay. It was
      found that oxoplatin can bind DNA directly without addition of a reducing agent.
      In addition, the antibodies elicited against DNA modified by cisplatin were not
      competitively inhibited by DNA modified by oxoplatin. However, DNA containing the
      adducts of oxoplatin became a strong inhibitor of these antibodies, if it was
      subsequently treated with ascorbic acid, which is a reducing agent. These results
      were interpreted to mean that oxoplatin can form DNA adducts containing the
      platinum moiety in the quadrivalent state. The direct irreversible binding of the
      platinum(IV) drug is, however, slow as compared to the reaction of its
      platinum(II) counterpart. It was also found that oxoplatin preferentially binds
      to guanine residues and can form DNA intrastrand and interstrand cross-links
      containing platinum(IV). The DNA adducts containing platinum(IV) can inhibit in
      vitro transcription by a prokaryotic DNA-dependent RNA polymerase. We find that
      the platinum(IV) complex binds to DNA at similar sites as its platinum(II)
      counterpart. On the other hand, the DNA adducts containing the platinum(II) or
      platinum(IV) analogues differ in the number of ligands and the formal charge on
      their platinum center. We suggest that these differences could be responsible for
      distinct conformational features and stability of DNA modified by platinum(II) or
      platinum(IV) complexes.

PMID- 7737156
TI  - Phosphorylation studies on rat p53 using the baculovirus expression system.
      Manipulation of the phosphorylation state with okadaic acid and influence on DNA
      binding.
AB  - To elucidate the role of phosphorylation of p53 we used the baculovirus
      expression system to obtain high yields of protein eventually in distinct
      phosphorylation states. Initially, we obtained only marginal phosphorylation,
      despite high levels of expression. Two-dimensional phosphopeptide maps exhibited
      the same pattern as known from rat cells although some sites were
      underrepresented. Coexpression of simian virus 40 (SV40) large T antigen or
      cyclin-dependent kinases, cdc2 or cdk2, had only marginal effects on the
      phosphorylation state of p53. However, when we employed the phosphatase inhibitor
      okadaic acid, overall phosphorylation of p53 was drastically enhanced in a dose
      dependent manner and resembled that of p53 from SV40-transformed rat cells. This
      hyperphosphorylation resulted in enhanced binding of a consensus oligonucleotide
      as revealed by electrophoretic mobility shift assays. To assess the role of
      individual phosphorylation sites, we generated a set of mutants at putative or
      identified sites. All mutants retained the ability to bind wild-type conformation
      specific antibody Pab1620, to complex with SV40 large T antigen, and to bind to
      the consensus oligonucleotide. Moreover, most mutants exhibited enhanced DNA
      binding upon okadaic acid treatment, except for a mutant at the cdk site which
      failed to do so. These data show that: (a) insect cells contain all the protein
      kinases necessary for phosphorylation of a mammalian protein, p53; (b) in insect
      cells the ratio of kinase/phosphatase activities differs from that in mammalian
      cells so that underphosphorylation of recombinant proteins in this system may
      result from high phosphatase activities rather than saturation of kinases with
      recombinant substrate; (c) the system can be manipulated to obtain subpopulations
      of recombinant protein in a desired phosphorylation state, and (d)
      phosphorylation may regulate the DNA-binding activity of p53.

PMID- 7737157
TI  - The energy conserving N5-methyltetrahydromethanopterin:coenzyme M
      methyltransferase complex from Methanobacterium thermoautotrophicum is composed
      of eight different subunits.
AB  - N5-Methyltetrahydromethanopterin:coenzyme M methyltransferase (Mtr) from
      Methanobacterium thermoautotrophicum strain Marburg is a membrane-associated
      enzyme complex which catalyzes an energy-conserving, sodium-ion-translocating
      step in methanogenesis from H2 and CO2. We report here that the complex is
      composed of eight different subunits for which evidence was obtained at the
      protein, DNA and RNA levels: (a) SDS/PAGE of the purified complex revealed the
      presence of eight different polypeptides of apparent molecular masses of 34
      (MtrH), 28 (MtrE), 24 (MtrC), 23 (MtrA), 21 (MtrD), 13 (MtrG), 12.5 (MtrB) and 12
      kDa (MtrF). The N-terminal amino acid sequences of the 12-, 12.5- and 13-kDa
      polypeptides, which had previously not been accessible, were determined; (b)
      cloning and sequencing of the corresponding genes revealed the presence of the
      eight mtr genes organized in a 4.9-kbp gene cluster in the order mtrEDCBAFGH; (c)
      Northern-blot analysis revealed the presence of a 5-kbp transcript. DNA probes
      derived from the mtrE and mtrH genes hybridized to the transcript, indicating
      that the eight mtr genes are organized in a transcription unit. By primer
      extension, the 5' end of the mtrEDC-BAFGH mRNA was analyzed. The mtr operon was
      found to be located between the methyl-coenzyme M reductase I operon (mcr) and a
      downstream open reading frame predicted to encode a Na+/Ca2+, K+ exchanger.

PMID- 7737158
TI  - The thermal unfolding of hevein, a small disulfide-rich protein.
AB  - Differential scanning calorimetry was used to study the thermal unfolding of
      hevein, a 43-residue disulfide-rich protein whose three-dimensional structure has
      been determined by X-ray diffraction. In the range pH 2.0-3.7 this process was
      approximately 75% reversible as judged by repeated scans on the same sample. The
      ratios of van'tr Hoff to calorimetric enthalpies were considerably larger than
      one, suggesting that intermolecular cooperation is involved in the unfolding of
      this protein. Alternatively, it is possible that the partial irreversibility of
      this process may cause distortions of the endotherm that affect the calculation
      of the van't Hoff enthalpy. Experimental changes in heat capacity and enthalpy
      were compared with those calculated from polar and nonpolar surface areas buried
      in the native state. It was found that when the unfolded state is represented as
      an extended chain without disulfide cross-links, experimental and calculated
      parameters agree well. However, if the unfolded protein is modeled with the
      presence of disulfide bridges, the agreement between the two sets of parameters
      is lost. The entropy change/residue at 112 degrees C is considerably smaller than
      the average value for globular proteins, thus suggesting that, as expected,
      disulfide bonds strongly influence the entropy of the unfolded state of this
      protein.

PMID- 7737159
TI  - The crystal structure of nickel(II)-azurin.
AB  - The nickel(II)-azurin metalloderivative has been crystallized and its structure
      solved at 0.205-nm resolution by X-ray diffraction. The overall structure is not
      modified by the metal exchange and the only differences with regard to the native
      copper(II)-azurin occur in the metal site region. These variations affect
      principally the axial ligands. Nickel co-ordinates more strongly to the carbonyl
      oxygen of Gly45 while its distance to the Met121 S4 enlarges up to 0.330 nm. The
      resulting metal center structure is intermediate between those of the Cu(II) and
      Zn(II) azurins, and can be described as distorted tetrahedral. However, the
      existence of contact interaction between Met121 and the nickel ion is still
      possible as has been shown by paramagnetic 1H-NMR studies in solution.

PMID- 7737160
TI  - The complete primary structure of glycosylated porcine platelet factor 4.
AB  - We have purified platelet factor 4 from porcine platelets and shown that it is
      glycosylated. The purified protein migrated as a broad band at approximately
      14,000 Da, characteristic of glycoproteins. Electrospray mass spectroscopy of the
      intact protein gave a predominant mass of 11,111 Da, with a minor component of
      10,804 Da. Sialidase digestion reduces both forms to a single mass of 10,497 Da.
      Upon Edman degradation, the amino terminus was found to be blocked by the
      presence of a pyroglutamate residue. We have determined the complete primary
      structure of platelet factor 4 by peptide mapping and Edman degradation, thereby
      completing information on the amino-terminal and carboxy-terminal regions which
      is missing in the previously published partial sequence. Sequencing of the intact
      and deglycosylated protein show that the glycosylation site is at Thr8. The amino
      acid composition accounts for a mass of 9623 Da, and the carbohydrate moeity was
      found to contribute 1490 Da. The biological activity of the porcine protein has
      been compared to recombinant human platelet factor 4 in an endothelial cell
      proliferation assay; both inhibit at a concentration giving half the maximal
      inhibition of 0.1 microM. Removal of the 19 amino-terminal residues carrying the
      carbohydrate moiety results in no change in the biological activity.

PMID- 7737161
TI  - Correlation of carbon monoxide association rates and the position of absorption
      band III in hemoproteins.
AB  - We have examined the absorbance of a charge-transfer transition near 760 nm,
      known as band III, in several hemoproteins and heme complexes. The band III
      position correlates with the rate of carbon monoxide binding to the heme. A band
      III present at 760 nm indicates an unfavorable geometry of the heme for carbon
      monoxide binding; a red-shift of the band III to 765 nm indicates a less
      constrained geometry of the heme as evidenced by higher carbon monoxide
      association rates. The band III position correlates well with the Raman frequency
      of the Fe-His(F8) bond as suggested previously for normal hemoglobin A
      [Sassaroli, M. & Rousseau, D. L. (1987) Biochemistry 26, 3092-3098]. Aplysia
      myoglobin and the chimeric heme protein kinase FixL from Bradyrhizobium
      japonicum, hemoproteins with an apolar residue in place of the highly conserved
      polar histidine E7, do not fit the relationship between the band III position and
      the rate of binding of carbon monoxide to the heme. With these few exceptions,
      the measurement of band III appears to be a practical means to probe the stretch
      frequency of the Fe-His(F8) bond.

PMID- 7737162
TI  - Autophosphorylation of PC-1 (alkaline phosphodiesterase I/nucleotide
      pyrophosphatase) and analysis of the active site.
AB  - PC-1 is an ecto-enzyme possessing alkaline phosphodiesterase I (EC 3.1.4.1) and
      nucleotide pyrophosphatase (EC 3.6.1.9) activities. It has also been proposed to
      be an ecto-protein kinase capable of phosphorylating itself as well as exogenous
      proteins. We have investigated the phosphorylation capability of PC-1 and have
      developed a novel method for its detection and characterization based on
      autophosphorylation, which allows detection without the use of antibodies. When
      cells expressing membrane PC-1 were held on ice with [gamma-32P]ATP, SDS/PAGE of
      whole cell lysates showed a single band which was PC-1; this band was absent in
      cells not expressing PC-1. Immunoprecipitates of soluble PC-1 isolated from
      culture supernatants of cells expressing PC-1 were also capable of
      autophosphorylation, and the size of the labeled protein was the same as
      previously reported for soluble PC-1. PC-1 was also labeled with [alpha-32P]ATP
      and [35S]dATP[alpha S]. We found no evidence that PC-1 was capable of
      phosphorylating proteins other than itself, and conclude that it is not a true
      kinase, and that the observed labeling with [gamma-32P]ATP, [alpha-32P]ATP and
      [35S]dATP[alpha S] reflect transient covalent adducts that are part of the
      catalytic cycle of phosphodiesterase/pyrophosphatase activity rather than
      intrinsic kinase activity. Mutation of the active-site threonine to tyrosine,
      serine or alanine reduced the 5'-nucleotide phosphodiesterase activity of PC-1
      and its ability to autophosphorylate to undetectable levels. Together, these data
      suggest that both activities depend on the same site.

PMID- 7737164
TI  - Characterization of monomeric 4-aminobutyrate aminotransferase at low pH.
AB  - 4-Aminobutyrate aminotransferase undergoes a reversible process of
      association/dissociation at low pH. At pH 5.0, monomeric species exist
      predominantly in solution as revealed by FPLC and time-dependent emission
      anisotropy measurements. The observed rotational correlation time at pH 5.0, phi
      obs = 25 ns, corresponds to a compact spherical unit of 52 kDa. An increase in
      the net charge of the macromolecule at pH 5.0 is responsible for destabilization
      of the dimeric structure, (WEL approximately 41.84 kJ/mol), but the dissociation
      of the protein does not perturb the secondary structure as revealed by CD
      measurements. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS), bound
      to hydrophobic sites of the enzyme, was used to monitor the kinetics of protein
      dissociation by stopped-flow spectroscopy. The dissociation of the dimeric
      structure at pH 5.0 was characterized by a relaxation time of 18 ms. The rate of
      association of monomeric subunits at pH 7.0 was too fast to be detected in the
      stopped-flow instrument. These observations have some bearing on the mechanism of
      reconstitution of dimeric structures of 4-aminobutyrate aminotransferase in the
      cell.

PMID- 7737165
TI  - Oligosaccharyl transferase is a constitutive component of an oligomeric protein
      complex from pig liver endoplasmic reticulum.
AB  - Oligosaccharyl transferase (OST), an intrinsic component of the endoplasmic
      reticulum membrane, catalyses the N-glycosylation of specific asparagine residues
      in nascent polypeptide chains. We have purified the enzyme from crude pig liver
      microsomes by a procedure involving salt/detergent extraction, concanavalin-A
      precipitation, S-Sepharose, MonoP and concanavalin-A-Sepharose chromatographies.
      A highly purified OST preparation exerting catalytic activity, contained two
      protein subunits of 48 kDa and 66 kDa, from which the 66-kDa species was
      identified by immunoblotting as ribophorin I. The function of ribophorin I in
      this dimeric protein complex is unknown. The high degree of similarity between
      its transmembrane region and a putative dolichol-recognition consensus sequence
      suggests that ribophorin I could be involved in glycolipid binding and delivery.
      Several lines of evidence indicate that the catalytically active 48-kDa/66-kDa
      polypeptides are associated in the endoplasmic reticulum membrane with other
      proteins, including ribophorin II and a 40-kDa glycoprotein. The implication of
      ribophorins I and II in the translocation machinery and their apparent
      association with the OST activity point to a close relationship between
      polypeptide synthesis, translocation and N-glycosylation, both spacially and
      temporally. Kinetic studies with the MonoP-purified oligosaccharyl transferase
      showed that the enzyme transfers dolichyl-diphosphate-linked GlcNAc2 to synthetic
      tripeptides and hexapeptides, containing the Asn-Xaa-Thr motif, at a comparable
      rate. The glycosylation reaction was found to have a pH optimum close to 7 and to
      require divalent metal ions, with Mn2+ being most effective. Substitution of
      threonine in the N-glycosylation motif by serine impairs its function as an
      acceptor, measured by Vmax/Km, by approximately 17-fold, consisting of a 7.3-fold
      increase in Km and a 2.3-fold decrease in Vmax. This indicates that the side
      chain structure of the hydroxyamino acid influences both binding and catalysis,
      consistent with previous studies highlighting its participation in the catalytic
      mechanism of transglycosylation. The Km values of peptide acceptors improved
      significantly when dolichyl-phosphate-bound oligosaccharides were used instead of
      lipid-linked GlcNAc2 as the glycosyl donor. We conclude from this observation
      that the sugar residues on the outer branches of the glycolipid donor induce
      conformational changes in the active site of the oligosaccharyl transferase, thus
      influencing the association constant of the peptide substrate.

PMID- 7737166
TI  - A new cationic liposome encapsulating genetic material. A potential delivery
      system for polynucleotides.
AB  - The endeavour to enhance gene therapy has led to increased research on the
      development of simple, efficient and safe delivery systems. This study deals with
      the use of an artificial cationic lipid on the encapsulation of genetic material
      in liposomes. The addition of a biologically degradable cationic phospholipid,
      dipalmitoyl-L-alpha-phosphatidylethanolamine covalently coupled to L-lysine, in a
      standard liposome formulation allowed us to obtain vesicles with high entrapment
      of various polynucleotides. Polynucleotide degradation by nucleases is markedly
      prevented by these liposomes. The preparations were stable in both culture medium
      and human plasma. This latter finding is consistent with the weak binding of
      plasma proteins on the liposome surface. The efficiency of this new delivery
      system was demonstrated in antiviral assays. Finally, these liposomes displayed a
      relatively low cellular toxicity. All these findings indicate that these cationic
      vesicles are very suitable for genetic material vehiculation.

PMID- 7737163
TI  - 14CO2 exchange with acetoacetate catalyzed by dialyzed cell-free extracts of the
      bacterial strain BunN grown with acetone and nitrate.
AB  - The nitrate-reducing bacterial strain BunN is able to grow with acetone and
      nitrate under anoxic conditions. Dialyzed crude cell-free extracts of acetone
      plus-nitrate-grown cells of strain BunN catalyzed the exchange of 14CO2 into
      acetoacetate in an ADP-dependent reaction. The rates of exchange catalyzed by
      extracts of acetate-grown or 3-hydroxybutyrate-grown cells were only 13% of that
      catalyzed by extracts of acetone-grown cells. The activity was enzymic since it
      was destroyed by boiling and was proportional to the amount of added extract. The
      optimal acetoacetate concentration was 100 mM and the apparent Km was 11.1 mM.
      The pH optimum was 6.5, the exchange was not dependent on the addition of biotin,
      and the activity was not inhibited by avidin. The exchange activity was not
      stimulated (less than two fold) by a variety of metal ions or by a range of
      possible cofactors. Under optimal conditions (100 mM acetoacetate, 5 mM ADP, 10
      mM NaHCO3, pH 6.5, under N2), the exchange activity was 2.7 nmol.min-1.mg protein
      1; 2% of the in vivo carboxylation activity of acetone-plus-nitrate-grown
      cultures. It is suggested that the exchange reaction is a partial reaction
      catalyzed by the enzyme (or enzyme complex) that carboxylates acetone, and that
      the methods developed in this study provide a means with which to investigate
      this reaction further.

PMID- 7737167
TI  - Specific inhibition of plant fatty acid elongation by a long-chain cerulenin
      analogue.
AB  - Cerulenin analogues with 16 or 18 carbon atoms inhibit both ATP-dependent and
      acyl-CoA-dependent fatty acid elongations. Prior incubation of microsomes with
      inhibitors is necessary to obtain maximal inhibition. The analogues act on the
      first reaction of the elongation process catalysed by the 3-ketoacyl-CoA
      synthase. The 18-carbon analogue has no, or little, effect on the fatty acid
      synthesis, while cerulenin and its 16-carbon analogue totally inhibit this
      synthesis. The 18-carbon analogue appears to be a specific inhibitor of the
      synthesis of very long-chain fatty acids, with no effect on de novo fatty acid
      synthesis.

PMID- 7737168
TI  - Spatial compartmentation and time resolution of photooxidation of a cell membrane
      probe in electropermeabilized Chinese hamster ovary cells.
AB  - When electropulsed by short strong electric field pulses, cells can be
      permeabilized transiently (electropermeabilization). The transient electroinduced
      membrane restructuration which supports enhanced membrane permeability is
      topologically well defined on the surface of the cell. Exchange of polar species
      only takes place on the part of the cell surface which is controlled by the field
      intensity. Electropermeabilization is a stress for the cell and metabolic
      responses associated with this stress must be studied. A key point is to discover
      whether this stress affects the whole cell surface or especially the
      permeabilized part. This was investigated by photochemical time-dependent
      methodology. Analysis of the photooxidation reaction of 5-(N-hexadecanoyl)
      aminofluorescein, an interfacial light-sensitive fluorescent probe, inserted into
      the Chinese hamster ovary cell membrane showed that the rate of reaction was
      accelerated when the cell population was electropermeabilized. This increase in
      the rate constant depended on the field strength. A theoretical approach
      suggested that modulation of the photooxidation reaction was restricted to the
      electropermeabilized part of the cell surface. The difference of reactivity could
      be correlated with an activator effect of oxygen-reactive species generated by an
      electro-induced oxidative jump and suggested that these species were localized in
      the permeabilized part of the plasma membrane. Using fluorescence digitized
      videomicroscopy imaging on a single cell, such spatial heterogeneity of the
      photooxidation reaction was indeed directly observed when the cell was
      electropermeabilized. There was heterogeneous compartmentation of the membrane
      reaction into two independent domains with specific reactivity. The direct
      observation is that long-lived electropermeabilization only affects a restricted
      part of the pulsed cell surface, from both a structural and a metabolic point of
      view.

PMID- 7737170
TI  - A novel approach for investigating reaction mechanisms in cells. Mechanism of
      deoxy-trehalose synthesis in Saccharomyces cerevisiae studied by 1H-NMR
      spectroscopy.
AB  - A new approach is proposed for investigating the mechanism of metabolite
      synthesis in cells. This method, based on the competition between various
      substrates, allows the flux along a pathway, which is normally independent of the
      concentration of the corresponding precursor in the external medium, to be
      divided into partial fluxes. In particular, the mechanism deoxy-trehalose
      synthesis in glucose-grown repressed Saccharomyces cerevisiae was studied, by 1H
      NMR spectroscopy, using the competition between 2-deoxy-D-glucose (dGlc) and 2
      fluoro-deoxy-D-glucose (FdGlc) with respect to hexokinase. S. cerevisiae cells,
      suspended in a standard pyrophosphate medium containing about 5 x 10(7) cells/ml,
      were incubated with 30 mM glucose and various concentrations of dGlc and FdGlc.
      Apart from dGlc6P and FdGlc6P, trehalose and the dissacharides relative to dGlc,
      i.e. dideoxy-trehalose (dGlc-dGlc) and deoxytrehalose (dGlc-Glc), are observed
      while their analogues relative to FdGlc (FdGlc-FdGlc, FdGlc-Glc) are surprisingly
      absent. For the same external concentration of dGlc and FdGlc, the internal
      concentration of FdGlc6P is about three times larger than that of dGlc6P. The
      ratio of the FdGlc6P and dGlc6P concentrations is independent of the incubation
      times and proportional to the FdGlc and dGlc concentrations in the suspension.
      The dGlc6P concentration can thus be reduced at will by increasing the
      [FdGlc]/[dGlc] ratio. Under these conditions, the dGlc-Glc concentration was
      found to vary linearly with that of dGlc6P. The present data clearly show that
      deoxy-trehalose is not synthesized from UDP-dGlc and Glc6P but from UDP-Glc and
      dGlc6P. This conclusion was also confirmed by an experiment in which S.
      cerevisiae cells were previously charged with dGlc6P and then incubated with
      glucose.

PMID- 7737171
TI  - Comparative biochemical and molecular analysis of the Staphylococcus hyicus,
      Staphylococcus aureus and a hybrid lipase. Indication for a C-terminal
      phospholipase domain.
AB  - The lipase gene, geh, from Staphylococcus aureus NCTC8530 was cloned in
      Staphylococcus carnosus. DNA sequencing revealed an open reading frame (ORF) of
      2046 nucleotides encoding a 682-amino-acid protein with a molecular mass of 76900
      Da. Determination of the transcriptional start site revealed a 203-nucleotide
      mRNA leader. Expression of geh in the protease-negative S. carnosus
      (pT181copSA22) resulted in overexpression of a 83-kDa lipase found in the culture
      supernatant. N-terminal protein sequencing and sequence comparison with three
      other staphylococcal lipases suggest that this lipase is organised as a pre-pro
      enzyme. The substrate specificity of this lipase is different from the
      Staphylococcus hyicus lipase. The S. hyicus lipase expressed both a high Ca(2+)
      dependent phospholipase and lipase activity while the S. aureus lipase lacked
      this phospholipase activity and its activity with tributyrylglycerol or p
      nitrophenyl octanoate is hardly stimulated by Ca2+ ions. A hybrid protein was
      constructed in which the C-terminal 146 residues of the S. hyicus lipase were
      substituted by 145 residues of the C-terminal of the S. aureus lipase, which
      contains the proposed active-site amino acids Asp602 and His641. The hybrid
      enzyme was still active and revealed an intermediary enzymic activity. The most
      striking effect was that it had lost the S. hyicus-specific phospholipase
      activity and that, in contrast to the two parental enzymes, its activity with p
      nitrophenyl octanoate became highly sensitive to the presence of Ca2+. These
      observations suggest that the C-terminal domain of the S. hyicus lipase strongly
      contributes to the binding pocket of the polar headgroup of phospholipids. The
      Ca(2+)-binding site seems to be located in the N-terminal fragment of the S.
      hyicus lipase. The fact that two closely related enzymes differ in the need for
      Ca2+ underscores the notion that it plays a structural rather than a catalytic
      role.

PMID- 7737169
TI  - Properties of the soluble polypeptide of the proton-translocating
      transhydrogenase from Rhodospirillum rubrum obtained by expression in Escherichia
      coli.
AB  - Transhydrogenase, which catalyses the reduction of NADP+ by NADH coupled to
      proton translocation across a membrane, may be unique in the photosynthetic
      bacterium Rhodospirillum rubrum. Unlike the homologous enzyme from animal
      mitochondria and other bacterial sources, it has a water-soluble polypeptide,
      which exists as a dimer (Ths), that can be reversibly dissociated from the
      membrane component [Williams, R., Cotton, N. P. J., Thomas, C. M. & Jackson, J.
      B. (1994) Microbiology, 140, 1595-1604]. We have expressed the gene for Ths in
      cells of Escherichia coli under control of the tac promoter and a strong ribosome
      binding site. The protein, purified by column chromatography, fully reconstituted
      transhydrogenation activity to everted membrane vesicles of Rhs. rubrum that had
      been washed to remove Ths. The purified expressed protein was prepared in
      quantities over 100-fold greater than were obtained from wild-type Rhs. rubrum.
      The fluorescence spectrum of purified expressed Ths had an intense and unusually
      short wavelength emission maximum at 310 nm with shoulders at 298 and 322 nm.
      Time-resolved measurements indicated that the fluorescence decay was almost
      monoexponential with a lifetime of 5.2 ns. On denaturation with 4 M guanidine
      hydrochloride, the emission band shifted to 352 nm and decreased in intensity. In
      the native protein, the fluorophore was relatively inaccessible to quenching
      solutes, such as iodide ions and acrylamide. It is concluded that the
      fluorescence emission arises mainly from the single tryptophan residue of Ths
      (Trp72), which is locked into a rigid conformation and is located in highly non
      polar environment. The 310-nm fluorescence of Ths was quenched by NADH, maximally
      to 46%. The apparent binding constant was 18 microM. The fluorescence of Ths
      bound NADH was enhanced relative to the nucleotide in free solution and its
      emission maximum was shifted to a shorter wavelength (440 nm). These data support
      previous indications that the NADH binding site is located in domain I of proton
      translocating transhydrogenase. Excitation of Ths at 280 nm did not lead to
      sensitized emission at 440 nm from bound NADH. This indicates that the quenching
      of fluorescence of Ths by NADH does not result from resonance energy transfer
      from Trp72 to the bound nucleotide. NAD+, NADP+ and NADPH had little effect on
      the protein fluorescence. The kinetics of quenching of Ths fluorescence by NADH
      were examined after mixing in a stopped-flow device. The 'on' rate constant for
      nucleotide binding was approximately 8 x 10(6) M-1 s-1 and the 'off' constant
      approximately 150 s-1.

PMID- 7737172
TI  - The gag homologue of retrotransposon Ty1 assembles into spherical particles in
      Escherichia coli.
AB  - Expression of TyA (reading frame A) of the yeast retrotransposon Ty1 in
      Escherichia coli is possible by using efficient transcriptional and translational
      initiation signals. When expressed in E. coli, the gag homologue of Ty1 assembles
      into spherical particles similar, but not identical to virus-like particles in
      the natural host of Ty1, Saccharomyces cerevisiae. Deletion analysis reveals a
      domain in the C-terminus of TyA that is essential for the assembly process. These
      findings indicate that an early step of the retroelement life cycle, assembly of
      the gag homologue into spherical particles, does not depend on specific host
      factors. The experiments also demonstrate that Ty1 Gag fusion proteins, potential
      tools for immunization, can be produced in E. coli, an organism that lacks
      endogenous retrotransposons.

PMID- 7737173
TI  - Site-directed mutagenesis of the redox-active cysteines of Trypanosoma cruzi
      trypanothione reductase.
AB  - The gene for trypanothione reductase from the Silvio strain of Trypanosoma cruzi
      has been cloned, sequenced and overexpressed in Escherichia coli using the
      constitutive lpp promoter on the expression plasmid pBSTNAV. Up to 13% of the
      total soluble protein is enzymically active trypanothione reductase with kinetic
      properties similar to the enzyme purified from T. cruzi. In order to assess the
      catalytic role of the putative active-site cysteine residues (C53 and C58), three
      mutant proteins have been constructed by site-directed mutagenesis substituting
      alanine or serine residues for cysteine; [C53A]trypanothione reductase,
      [C53S]trypanothione reductase and [C58S]trypanothione reductase. Although the
      purified, recombinant mutant proteins were catalytically inactive with NADPH and
      trypanothione disulphide as substrates, all showed comparable levels of
      transhydrogenase activity between NADPH and thio-NADP+, suggesting that the
      mutant proteins had correctly folded in vivo. All three mutants showed
      substantially different catalytic parameters for thio-NADP+ than the wild-type
      enzyme, presumably as a consequence of modifying the environment of the enzyme
      bound flavin, thereby altering its chemical reactivity. The purified
      [C58S]trypanothione reductase showed spectral properties similar to the oxidised
      wild-type enzyme but, unlike the wild-type enzyme, did not acquire the
      characteristic charge-transfer complex of the EH2 form on addition of NADPH. In
      contrast, in the absence of NADPH both [C53A]trypanothione reductase and
      [C53S]trypanothione reductase showed spectral properties similar to the EH2 form
      of the wild-type enzyme. These data indicate that both C53 and C58 are essential
      for overall catalysis, with the thiolate anion of C58 interacting with the enzyme
      bound FAD and C53 interacting with the disulphide substrate. These mutants should
      be useful in crystallographic studies of reaction intermediates which cannot be
      obtained with the catalytically active native enzyme.

PMID- 7737174
TI  - Effects of novel analogues of D-glucose on glycogen phosphorylase activities in
      crude extracts of liver and skeletal muscle.
AB  - The inhibitory properties of a series of both N-linked and C-linked C1
      substituted glucose derivatives towards glycogen phosphorylase (GP) activity from
      crude extracts of rat liver and muscle have been measured. The most effective
      inhibitor was N-acetyl-beta-D-glucopyranosylamine, which has Kis of 51 microM
      (muscle GPa), 30 microM (muscle GPb), 2.7 mM (liver GPa) and 4 mM (liver GPb).
      All analogues tested inhibit muscle GP more potently than liver GP, highlighting
      some differences between the two isoenzymes, which are nearly 80% similar. The
      human liver GP enzyme has been modelled on the basis of the rabbit muscle
      structure and, together with comparison of structures of muscle GPa and GPb, has
      provided some insights into possible explanations for the different properties of
      the two isoenzymes. Maximal activities of GP have also been measured in tissues
      from diabetic (db/db) and wild-type (db/+) mice. Liver GP from db/db mice
      exhibits higher activity [132% (a)-67% (b)] than from db/+ controls, although
      similar activities were observed for muscle GP from both db/db and db/+ animals.

PMID- 7737176
TI  - The DNA-binding site of the RecA protein. Photochemical cross-linking of Tyr103
      to single-stranded DNA.
AB  - To investigate the DNA-binding site in the Escherichia coli RecA protein, RecA
      was covalently cross-linked to oligodeoxythymidine [p(dT)14] by irradiation with
      ultraviolet light. We identified the site of cross-linking of the protein when
      the RecA.p(dT)14 complex was formed in the absence of nucleotide cofactor as well
      as in the presence of adenosine 5'-[gamma-thio]triphosphate. When RecA.p(dT)14
      complex formed without nucleotide cofactor was irradiated with ultraviolet light,
      a cross-linked peptide was found after digestion with Achromobactor lyticus
      protease I. Amino acid composition of the peptide was determined. The results
      indicated that the site of cross-linking was in the region spanning amino acid
      residues 89-106. Further digestion of the cross-linked fragment with
      Staphylococcus aureus V8 protease indicated that Tyr103 was the site of cross
      linking. When the complex formed with adenosine 5'-[gamma-thio]triphosphate was
      irradiated with ultraviolet light, two cross-linked sites were detected, which
      were in the region of residues 89-106 and residues 178-183. These regions are far
      from the two disordered loops in the crystal structure, which were suggested to
      be DNA-binding sites by Story et al. [Story, R. M., Weber, T. W. & Steitz, T. A.
      (1992) Nature 355, 318-325].

PMID- 7737175
TI  - Limitations to in vivo import of hydrophobic proteins into yeast mitochondria.
      The case of a cytoplasmically synthesized apocytochrome b.
AB  - The apocytochrome b gene, exclusively encoded by the mitochondrial genome, was
      engineered so that it could be expressed in the yeast cytoplasm. Different
      combinations of the apocytochrome b transmembrane domains were produced in the
      form of hybrid proteins fused to both the N-terminal mitochondrial targeting
      sequence of the ATPase subunit 9 from Neurospora crassa and to a cytoplasmic
      version of the bI4 RNA maturase, localised on the N-terminal and C-terminal
      sides, respectively, of the hydrophobic stretches. The bI4 RNA maturase, which
      can complement mitochondrial mutations, was used as an in vivo reporter to assess
      the mitochondrial import of the different groups of transmembrane helices. This
      new, reliable and sensitive reporter activity allowed us to experimentally
      determine the limitations to the mitochondrial import of hydrophobic proteins.
      All eight transmembrane helices of apocytochrome b could be imported into
      mitochondria, either alone or in combination, but no more than three to four
      transmembrane helices could be imported together at one time. This limit is close
      to that observed in the population of nuclear-encoded mitochondrial proteins. The
      hydrophobic characteristics of engineered and natural proteins targeted to the
      mitochondrial inner membrane revealed two factors important in the import
      process. These were (a) the local hydrophobicity of a transmembrane segment, and
      (b) the average regional hydrophobicity of the protein over an extended length of
      60-80 residues. Such features may have played a major role in the evolution of
      mitochondrial genomes.

PMID- 7737177
TI  - Interaction of Tyr103 and Tyr264 of the RecA protein with DNA and nucleotide
      cofactors. Fluorescence study of engineered proteins.
AB  - To obtain structural insight on the interaction of the RecA protein with
      nucleotide cofactors (ATP and ADP) and DNA, we have made two engineered RecA
      proteins, in which either Tyr103 or Tyr264 was replaced with tryptophan. The
      fluorescence of tryptophan residues (two/subunit) of wild-type RecA is not
      significantly altered upon the binding of cofactor or DNA. Therefore, any
      detectable fluorescence change of the engineered proteins could be directly
      related to interaction with the particular inserted tryptophan residue. The
      fluorescence of Trp103 is almost completely quenched upon ADP binding, supporting
      a stacking interaction of adenine base of ADP with Tyr103. By contrast, with ATP
      the quenching of fluorescence of Trp103 is not complete (75%), possibly
      indicating that there is no stacking interaction with ATP. Such a difference
      could explain the antagonistic effects of ATP and ADP. Both nucleotides partially
      quench the fluorescence of Trp264 (about 70%), confirming that this residue is in
      the vicinity of the cofactor-binding site. The binding of ssDNA also decreases
      the fluorescence of both Trp103 and Trp264, the degree of quenching depending
      upon base composition and decreasing in the following order: poly(dT) > poly(dI)
      > M13 ssDNA > poly(dA). This order coincides with that of the binding affinities
      of these polynucleotides to RecA reported by Cazenave et al. [Cazenave, C.,
      Chabbert, M., Toulme, J. J. & Helene, C. (1984) Biochim. Biophys. Acta 781, 7
      13]. This correlation supports the finding that a region very close to Tyr103
      interacts with DNA.

PMID- 7737178
TI  - The tetracyclic lantibiotic actagardine. 1H-NMR and 13C-NMR assignments and
      revised primary structure.
AB  - The primary structure of the peptide lantibiotic actagardine was determined in
      (2H3)acetonitrile/H2O by homonuclear two- and three-dimensional NMR spectroscopy
      as well as 2D 1H(13C) correlation spectra at natural abundance. Actagardine was
      found to be a tetracyclic 19-residue peptide containing one lanthionine and three
      overlapping beta-methyllanthionine bridges. Sequential resonance assignment and
      location of the four thioether rings was accomplished by 2D NOESY, 3D NOESY-TOCSY
      and gradient-enhanced 1H(13C)-HMBC spectra. The C-terminal thioether bridge was
      shown to be oxidized to a sulfoxide. The NMR data were additionally confirmed by
      mass spectrometry and Edman degradation after chemical modification, which
      allowed sequencing of lanthionine and beta-methyllanthionine residues. Our
      studies clearly show, that the structure of actagardine as previously published
      by Kettenring et al. (1990) J. Antibiot. 43, 1082-1088 is not correct.

PMID- 7737179
TI  - Lactose-specific enzyme II of the phosphoenolpyruvate-dependent
      phosphotransferase system of Staphylococcus aureus. Purification of the histidine
      tagged transmembrane component IICBLac and its hydrophilic IIB domain by metal
      affinity chromatography, and functional characterization.
AB  - The lactose-specific integral-membrane-protein enzyme II (IICBLac) of the
      bacterial phosphoenolpyruvate-dependent phosphotransferase system of
      Staphylococcus aureus catalyses the uptake and phosphorylation of lactose. It
      consists of an N-terminal membrane-spanning IIC domain and a C-terminal
      hydrophilic IIB domain. IICBLac was fused with a C-terminal tag of six histidine
      residues using recombinant DNA technology. The resulting protein, IICBLac-His,
      was produced in Escherichia coli and purified under nondenaturing conditions to
      homogenity. The purification procedure consists of a NaOH extraction step
      followed by solubilisation with Triton X-100, and metal-affinity chromatography
      using Ni(2+)-nitrilotriacetic acid resin. The purified recombinant His-tagged
      protein possessed substrate specificity identical to that of the wild-type
      protein. To investigate the hydrophilic IIB domain, the DNA sequence coding for
      IIB and the His tag were fused in-frame to a DNA sequence specific for an
      initiation signal. The overproduced recombinant IIBLac-His was obtained by metal
      affinity chromatography in pure form. Bacterial phosphotransferase-system
      dependent phosphorylation of IIB-His was demonstrated in a photometric assay and
      by urea/polyacrylamide gel electrophoresis. The phosphorylation activity of the
      mutant protein [C476S]-IICBLac, containing the mutagenized phosphorylation site,
      was restored in the presence of IIBLac-His in a phosphorylation assay.

PMID- 7737180
TI  - Carbohydrate structure analysis of batroxobin, a thrombin-like serine protease
      from Bothrops moojeni venom.
AB  - The carbohydrate side chains of batroxobin were liberated from tryptic
      glycopeptides by treatment with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine
      amidase F, pyridylaminated and separated by two-dimensional HPLC. Neutral
      oligosaccharide derivatives obtained after desialylation were characterized by
      methylation analysis, liquid secondary-ion mass spectrometry, digestion with
      exoglycosidases and endoglycosidases and, in part, by acetolysis, whereas sialic
      acid constituents were identified by reverse-phase HPLC after conjugation with
      1,2-diamino-4,5-methylene-dioxybenzene. The overall glycosylation status of the
      protein was studied by matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS). The results revealed that batroxobin is
      heterogeneously glycosylated carrying predominantly diantennary, partially
      incomplete complex-type glycans in addition to hybrid-type species. Most glycans
      were core-fucosylated at C6 of the innermost GlcNAc. As a characteristic feature,
      galactose was completely replaced by GalNAc beta 4-substituents in complex-type
      antennae, the GlcNAc-residues of which were, in part, fucosylated at C3.
      Furthermore, evidence was obtained that suggested the presence of a novel type of
      glycoprotein-N-glycan comprising two GalNAc beta 4GlcNAc beta 4GlcNAc beta 2Man
      antennae. Sialic acid residues represented a mixture of N-acetylneuraminic acid
      (Neu5Ac) and N-acetyl-4-O-acetylneuraminic acid (Neu4,5Ac2), which were
      exclusively linked to C3 of subterminal GalNAc. A precise assignment of these
      sialic acid derivatives to distinct oligosaccharide structures or antennae,
      however, was not carried out. Finally, MALDI-TOF-MS demonstrated that both
      potential N-glycosylation sites of batroxobin are substituted by carbohydrate
      chains. In conclusion, our studies revealed that this snake venom glycoprotein is
      characterized by a unique oligosaccharide pattern partly comprising novel
      structural elements.

PMID- 7737181
TI  - Recombinant human-milk bile-salt-stimulated lipase. Functional properties are
      retained in the absence of glycosylation and the unique proline-rich repeats.
AB  - Human milk bile-salt-stimulated lipase ensures efficient utilization of milk
      lipid in breast-fed infants. The N-terminal two-thirds of the peptide chain is
      highly conserved and shows striking similarities to typical esterases. In
      contrast, the remaining C-terminal part consists of a unique sequence of 16
      proline-rich O-glycosylated repeats of 11 residues each. Recently we could show,
      using recombinant lipase variants, that neither these repeats nor the single N
      linked sugar chain are essential for catalytic efficiency. In the present study,
      we report on the lack of importance of glycosylation and the unique repeats for
      other important functional properties, i.e. bile-salt activation, heparin
      binding, heat stability, stability at low pH and resistance to proteolytic
      inactivation. Compared to native enzyme, recombinant full-length lipase produced
      in two mammalian cell lines differed slightly in glycosylation pattern with no
      effects on the functional properties. Moreover, a variant lacking all repeats and
      the C-terminal tail following the last repeat exhibited the same functional
      characteristics as purified native milk enzyme. Thus, the structural basis for
      all the typical and functionally important properties reside in the N-terminal
      conserved part, in spite of the fact that none of these properties are shared by
      typical esterases. We could however, demonstrate that the C-terminal repeats are
      responsible for the unusual behaviour of the enzyme in size-exclusion
      chromatography, resulting in a considerably higher than expected apparent
      molecular mass.

PMID- 7737182
TI  - Proton NMR study of the trimannosyl unit in a pentaantennary N-linked
      decasaccharide structure. Complete assignment of the proton resonances and
      conformational characterization.
AB  - The chemical shifts of all the ring protons of the three Man residues in a
      pentaantennary glycan chain have been unambiguously assigned by two-dimensional
      proton nuclear magnetic resonance (1H-NMR) spectroscopic methods. The study,
      using chemical shift and J values on the conformation of the trimannosyl unit,
      revealed that the rotamer about the C5-C6 bond of the alpha 1-->6 linkage in the
      sequence of Man alpha 1-->6Man beta 1--> is predominantly confined to a gauche
      gauche rotamer (omega = 180 degrees, omega = O6-C6-C5-H5) and not to a gauche
      trans rotamer (omega = -60 degrees). We do not know of any previous demonstration
      that the dihedral angle omega (O6-C6-C5-H5) in Man alpha 1-->6Man beta 1--> is
      preferentially 180 degrees in complex-type N-linked glycans having no bisecting
      GlcNAc residue.

PMID- 7737183
TI  - X-ray structures of human neutrophil collagenase complexed with peptide
      hydroxamate and peptide thiol inhibitors. Implications for substrate binding and
      rational drug design.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases involved in
      tissue remodeling. They have also been implicated in various disease processes
      including tumour invasion and joint destruction and are therefore attractive
      targets for inhibitor design. For rational drug design, information of inhibitor
      binding at the atomic level is essential. Recently, we have published the refined
      high-resolution crystal structure of the catalytic domain of human neutrophil
      collagenase (HNC) complexed with the inhibitor Pro-Leu-Gly-NHOH, which is a mimic
      for the unprimed (P3-P1) residues of a bound peptide substrate. We have now
      determined two additional HNC complexes formed with the thiol inhibitor
      HSCH2CH(CH2Ph)CO-L-Ala-Gly-NH2 and another hydroxamate inhibitor, HONHCOCH(iBu)CO
      L-Ala-Gly-NH2, which were both refined to R-values of 0.183/0.198 at 0.240/0.225
      nm resolution. The inhibitor thiol and hydroxamate groups ligand the catalytic
      zinc, giving rise to a slightly distorted tetrahedral and trigonal-bipyramidal
      coordination sphere, respectively. The thiol inhibitor diastereomer with S
      configuration at the P1' residue (corresponding to an L-amino acid analog) binds
      to HNC. Its peptidyl moiety mimics binding of primed (P1'-P3') residues of the
      substrate. In combination with our first structure a continuous hexapeptide
      corresponding to a peptide substrate productively bound to HNC was constructed
      and energy-minimized. Proteolytic cleavage of this Michaelis complex is probably
      general base-catalyzed as proposed for thermolysin, i.e. a glutamate assists
      nucleophilic attack of a water molecule. Although there are many structural and
      mechanistic similarities to thermolysin, substrate binding to MMPs differs due to
      the interactions beyond S1'-P1'. While thermolysin binds substrates with a kink
      at P1', substrates are bound in an extended conformation in the collagenases.
      This property explains the tolerance of thermolysin for D-amino acid residues at
      the P1' position, in contrast to the collagenases. The third inhibitor,
      HONHCOCH(iBu)CO-L-Ala-Gly-NH2, unexpectedly binds in a different manner than
      anticipated from its design and binding mode in thermolysin. Its hydroxamate
      group obviously interacts with the catalytic zinc in a favourable bidentate
      manner, but in contrast its isobutyl (iBu) side chain remains outside of the S1'
      pocket, presumably due to severe constraints imposed by the adjacent planar
      hydroxamate group. Instead, the C-terminal Ala-Gly-NH2 tail adopts a bent
      conformation and inserts into this S1' pocket, presumably in a non-optimized
      manner. Both the isobutyl side chain and the C-terminal peptide tail could be
      replaced by other, better fitting groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737184
TI  - Tyrosine kinase activity of a chimeric insulin-like-growth-factor-1 receptor
      containing the insulin receptor C-terminal domain. Comparison with the tyrosine
      kinase activities of the insulin and insulin-like-growth-factor-1 receptors using
      a cell-free system.
AB  - In a previous study, we showed that a chimeric insulin-like-growth-factor-1 (IGF
      1) receptor, with the beta subunit C-terminal part of the insulin receptor was
      more efficient in stimulating glycogen synthesis and p44mapk activity compared to
      the wild-type IFG-1 receptor [Tartare, S., Mothe, I., Kowalski-Chauvel, A.,
      Breittmayer, J.-P., Ballotti, R. & Van Obberghen, E. (1994) J. Biol. Chem. 269,
      11449-11455]. These data indicate that the receptor C-terminal domain plays an
      important role in the transmission of biological effects. To understand the
      molecular basis of the differences in receptor specificity, we studied the
      characteristics of insulin, IGF-1 and chimeric receptor tyrosine kinase
      activities in a cell-free system. We found that, compared to wild-type insulin
      and IGF-1 receptors, the chimeric receptor showed a decrease in (a)
      autophosphorylation, (b) tyrosine kinase activity towards insulin receptor
      substrate-1 and the insulin receptor-(1142-1158)-peptide, and (c) the ability to
      activate phosphatidylinositol 3-kinase. However, for all the effects measured in
      a cell-free system, the chimeric receptor displayed an increased response to IGF
      1 compared to the native IGF-1 receptor. Concerning the cation dependence of the
      tyrosine kinase activity, we showed that, at 10 mM Mg2+, the ligand-stimulated
      phosphorylation of poly(Glu80Tyr20) by both insulin receptor and chimeric
      receptor was increased by Mn2+. Conversely at 50 mM Mg2+, the chimeric receptor
      behaved like the IGF-1 receptor, since the presence of Mn2+ decreased the
      stimulatory effect of IGF-1 on their kinase activity. Furthermore, the Km of the
      chimeric receptor for ATP was increased compared to the wild-type receptors.
      These data demonstrate that the replacement of the C-terminal tail of the IGF-1
      receptor by that of the insulin receptor has changed the receptor characteristics
      studied in a cell-free system. Our findings indicate that the C-terminal domain
      of the insulin receptor beta subunit plays a key role in regulation of the
      tyrosine kinase activity. The fine-tuning of the tyrosine kinase by the C
      terminal tail could participate in the receptor specificity.

PMID- 7737185
TI  - The solution structure of DNA duplex-decamer containing the (6-4) photoproduct of
      thymidylyl(3'-->5')thymidine by NMR and relaxation matrix refinement.
AB  - The DNA duplex-decamer containing a site-specific (6-4) photoadduct of
      thymidylyl(3'-->5')thymidine was generated by direct photolytic ultraviolet C
      irradiation of d(CGCATTACGC). The three-dimensional structure of the duplex (6-4)
      decamer, d(CGCAT[6-4]TACGC).d(GCGTAATGCG), has been determined by two-dimensional
      NMR spectroscopy and a relaxation matrix refinement method. NMR data and
      structural calculations established that the formation of the (6-4) adduct in the
      B-DNA duplex retains Watson-Crick-type hydrogen bonding throughout the duplex
      except at the 3'-side of the (6-4) lesion where the T-->C transition mutation is
      predominantly targeted [LeClerc, J. E., Borden, A. & Lawrence, C. W. (1991) Proc.
      Natl Acad. Sci. USA 88, 9685-9689], but leads to a 44 degrees bending in the
      overall DNA helix. Perpendicular base orientation of the (6-4) lesion provides a
      structural basis where potential hydrogen bonding at the 3' sides of the (6-4)
      adduct with substituted nucleotide is improbable during replication under
      stringent conditions.

PMID- 7737186
TI  - Isolation, characterization and expression of cationic peroxidase isozymes
      released into the medium of cultured tobacco cells.
AB  - Three glycoproteins of 34, 38 and 40 kDa were isolated from the spent medium of
      suspension-cultured tobacco cells. The 38-kDa and 40-kDa proteins were highly
      cationic peroxidases with indistinguishable enzymic properties but their
      structural difference was confirmed by sequence analysis of the amino-terminal
      regions and the recognition specificity of monoclonal antibodies. The 34-kDa
      protein was a moderately cationic peroxidase with enzymic properties quite
      different from those of the 38-kDa and 40-kDa enzymes. They were undetectable in
      the spent medium during the cell-proliferation phase but became abundant in the
      medium during the cell-expansion phase. This was confirmed quantitatively with
      the 40-kDa protein using the 40-kDa-specific monoclonal antibody. The mRNA
      expression for 40-kDa protein was at a constant basal level in the cell
      proliferation phase but increased in the cell-expansion phase.

PMID- 7737187
TI  - Expression and characterization of Geotrichum candidum lipase I gene. Comparison
      of specificity profile with lipase II.
AB  - Despite tremendous progress in the elucidation of three-dimensional structures of
      lipases, the molecular basis for their observed substrate preference is not well
      understood. In an effort to correlate the lipase structure with its substrate
      preference and to clarify the contradicting reports in the literature, we have
      compared the enzymic characteristics of two closely related recombinant lipases
      from the fungus Geotrichum candidum. These enzymes were expressed in the yeast
      Saccharomyces cerevisiae as fusions with an N-terminal poly(His) tag and were
      purified in a single step by metal-affinity chromatography. Their specific
      activities against a series of triacylglycerol substrates were compared using a
      titrimetric assay. The substrates varied in fatty acyl chain length, number of
      double bonds and their position along the chain. G. candidum lipases I and II
      (GCL I and GLC II) are markedly different with respect to their substrate
      preferences. For unsaturated substrates having long fatty acyl chains (C18:2 cis
      9, cis-12 and C18:3 cis-9, cis-12, cis-15), GCL I showed higher specific activity
      than GCL II, whereas GCL II showed higher specific activity against saturated
      substrates having short fatty acid chains (C8, C10, C12 and C14). We have
      constructed a hybrid molecule containing the N-terminal portion of GCL I
      (including the flap covering the active site) linked to the C-terminal portion of
      GCL II. The hybrid molecule showed a substrate preference pattern identical to
      that of GCL II. These results indicate that sequence variation within the N
      terminal 194 amino acids of G. candidum lipases do not contribute to the observed
      variation in efficiency by which the lipases hydrolyze their substrates.
      Moreover, it also shows that the flap region in GCL is not directly involved in
      substrate differentiation, even though this region is thought to be involved in
      recognition of the interface and in the activation of the enzyme.

PMID- 7737188
TI  - A serine protease zymogen in insect plasma. Purification and activation by
      microbial cell wall components.
AB  - A protease zymogen present in the plasma fraction of the hemolymph of silkworm,
      Bombyx mori, was purified to homogeneity as judged by SDS/PAGE and IEF/PAGE. An
      activating system for the zymogen was also isolated from the plasma fraction and
      was shown to be triggered by zymosan (yeast cell wall polysaccharide containing
      beta-1,3-glucan) or peptidoglycan. Using this system, the purified zymogen was
      activated and the active enzyme was purified to homogeneity. The physiological
      function of the zymogen or its active form is not yet known, but the active form
      was shown to have narrower substrate specificity than trypsin. Among 33 peptide
      derivatives examined, Boc-Gln-Arg-Arg-NH-Mec and Boc-Val-Pro-Arg-NH-Mec (Boc =
      tert-butoxycarbonyl, NH-Mec = 4-methylcoumaryl-7-amide) were the best and the
      second best substrates, respectively. The purified zymogen was determined to be a
      39-kDa protein consisting of a single polypeptide. The active form of the zymogen
      was labeled with [3H]diisopropylfluorophosphate and was completely inactivated by
      (p-amidinophenyl)methanesulfonyl fluoride. The molecular mass of the [3H]-labeled
      enzyme was determined to be 38 kDa in SDS/PAGE under reducing conditions. These
      results indicate that the 39-kDa protein purified in the present study is a
      zymogen of a serine-type protease and that the activation of the zymogen occurs
      by limited proteolysis.

PMID- 7737189
TI  - Cytochrome c reductase from potato does not comprise three core proteins but
      contains an additional low-molecular-mass subunit.
AB  - Analysis of cytochrome c reductase from potato by Tricine/SDS/PAGE reveals 10
      bands representing 10 different subunits. In comparison to glycine/SDS/PAGE one
      additional small protein becomes visible, whereas the three large core proteins
      are not resolved. The identity of the subunits was determined by immunoblotting
      and direct sequence determination. Sequence data for the novel small component
      were used to derive oligonucleotides for probing a potato cDNA-library and
      isolating corresponding clones. The newly identified subunit is a 6.7-kDa
      protein, that exhibits significant sequence similarity to a 8.5-kDa subunit of
      cytochrome c reductase from yeast and the 6.5-kDa iron-sulfur-protein-binding
      factor from the equivalent enzyme complex from beef. Also the potato 6.7-kDa
      subunit can be dissociated from the cytochrome c reductase complex together with
      the iron-sulfur protein. To address the question of whether three or two core
      subunits occur simultaneously in monomeric cytochrome c reductase complexes from
      potato, a peptide-specific antibody was generated. The antiserum is capable of
      discriminating between the 55-kDa and 53-kDa core proteins, which can be
      separated by glycine/SDS/PAGE and which were previously found to be structurally
      related. Immunoprecipitations of isolated cytochrome c reductase from potato
      using this antibody revealed an enzyme complex containing only two core proteins.
      The simultaneous occurrence of only two core subunits was confirmed by a
      comparison of the molecular masses of cytochrome c reductase from potato and beef
      by blue-native-gel electrophoresis. Hence the cytochrome c reductase complexes
      from potato, beef and yeast have a very conserved subunit composition. The
      evolutionary implications of these findings are discussed.

PMID- 7737190
TI  - Characterization of the two unique human anti-flavin monoclonal immunoglobulins.
AB  - Form A of two previously described human monoclonal anti-riboflavin IgGs, the GAR
      [Farhangi, M. & Osserman, E. F. (1976) N. Engl. J. Med. 294, 177-183] and DOT
      [Merlini, G., Bruening, R., Kyle, R. & Osserman, E. F. (1990) Mol. Immunol. 27,
      385-394], has been characterized in terms of binding properties and primary
      structure. Both forms were isolated as immunocomplexes with bound riboflavin and
      gave a reconstitutable apoprotein. The riboflavin-reconstituted IgGs showed a
      similar visible absorption spectrum, with a marked resolution of the 445-nm band
      and a ratio 445-nm/370-nm peaks of 1.13 for DOT and 1.19 for GAR. Both proteins
      bind riboflavin, FMN and FAD with a molar ratio ligand/protein of 2:1. DOT and
      GAR share a very similar affinity for the flavinic ligands; the Kd values for
      riboflavin and FMN are in the range 1 nM; that for FAD is an order of magnitude
      higher. DOT and GAR do not form an adduct between the nucleophilic group sulfite
      and the N(5) position of the flavin, and do not stabilize any flavinic
      semiquinone during reduction with the xantine/xantine oxidase benzylviologen
      system. The primary structure of fragment antigen binding (Fab) DOT and heavy
      chain variable region (VH) GAR determined in the present study and that already
      known for the light-chain variable region (VL) GAR [Kiefer, C. R., McGuire, B.
      S., Osserman, E. F. & Garver, F. A. (1983) J. Immunol. 131, 1871-1875] evidenced
      that the two IgGs are assembled with VL and VH chains of different subgroups; a
      lambda III/HIII pair in GAR, and a lambda II/HI pair in DOT. Although less
      similar each other than to the counterparts of the same subclasses, DOT and GAR
      share an exclusive identity in the VH CDR3 region.

PMID- 7737191
TI  - Increased membrane-protein methylation in hereditary spherocytosis. A marker of
      cytoskeletal disarray.
AB  - Protein carboxyl methyltransferase of type II selectively recognizes L
      isoaspartyl and D-aspartyl residues spontaneously occurring in proteins and
      peptide substrates. Membrane protein methylation levels increase with erythrocyte
      aging in circulation, in parallel with the spontaneous formation of abnormal
      aspartyl sites, due to protein intrinsic instability. We found that enzymic
      methyl esterification of erythrocyte membrane proteins in hereditary
      spherocytosis, a model of cytoskeletal disarray, is significantly increased
      compared to normal red blood cells. This cannot be explained by an increase in
      mean age of spherocytes, which are on the contrary significantly younger than
      control cells. No differences in cytosolic methyltransferase specific activity,
      as well as in the intracellular concentrations of the methyl donor
      adenosylmethionine and/or of the methylation inhibitor adenosylhomocysteine were
      observed. We identified bands 2.1, 4.1 and 4.2 as the main targets for increased
      methylation, whose levels were correlated with the degree of spectrin deficiency
      associated with this anemia. Our findings indicate that membrane-protein methyl
      esterification represents a marker of membrane structural alteration in vivo in
      spherocytosis. We hypothesize that either an increased accessibility of
      methylation sites normally not available to the methyltransferase, or accelerated
      formation of methyl-accepting sites in membrane proteins are present in
      spherocytosis.

PMID- 7737193
TI  - The effect of amino acids on the metabolic fate of 15NH4Cl in isolated sheep
      hepatocytes.
AB  - Ruminants characteristically absorb a large proportion of dietary nitrogen across
      the portal-drained viscera as ammonia nitrogen which is detoxified by conversion
      to urea in the liver. In theory, ammonia can supply both nitrogen atoms of the
      urea molecule via mitochondrial (carbamoyl phosphate) and cytoplasmic (aspartate)
      precursor pathways of the ornithine cycle but the effect of amino acids on the
      flux of nitrogen from ammonia to each of the two urea nitrogen atoms has not been
      determined. We report a study designed to determine the distribution of [15N]
      ammonia between [15N1]urea and [15N2]urea in sheep hepatocytes in response to
      ammonia concentrations (0.33, 0.67 and 1.00 mM) in the presence or absence of
      amino acids. In the absence of amino acids, the enrichment of [15N2]urea rose
      more rapidly during incubations than [15N1]urea and attained enrichments of 66
      88% within 5 min of incubation. At the end of 2.5 h of incubation, [15N2]urea
      represented 60% and 90% of the total urea molecules at low and high ammonia
      concentrations, respectively. The enrichments of glutamate and aspartate were
      similar to [15N1]urea in the cells at the end of the incubations, even in the
      presence of unlabelled amino acids, supporting the concept of mitochondrial
      ammonia being in equilibrium with cytosolic aspartate formation. In the presence
      of amino acids basal urea synthesis increased but ammonia uptake and 15NH4Cl
      conversion to urea was less than in the absence of amino acids. The rate of
      formation of [15N1]urea was greater in incubations containing amino acids but
      when ammonia concentration in the media was raised only [15N2]urea flux increased
      with no change in either [15N1]urea or the unlabelled species. Measurement of
      media amino acid concentrations after 2.5 h of incubation in the presence of
      amino acids revealed that arginine, glutamine, glycine and alanine were removed
      while there was net formation of aspartate, threonine, serine, glutamate, and the
      branched chain amino acids. However, less than 12% of the 15N transfer appeared
      in free amino acids. The increases in basal and unlabelled urea synthesis in the
      presence of amino acids could be numerically accounted as the sum of arginine and
      glutamine removal from incubations. It is concluded that in sheep hepatocytes
      15NH4Cl removal leads to quantitative formation of [15N2]urea, even in the
      presence of a physiological mixture of amino acids. The increase in the formation
      of the [15N1]urea in the presence of amino acids can be explained by the
      preferential utilisation of the amide nitrogen of glutamine for urea synthesis.

PMID- 7737192
TI  - Distinct functional properties of three human paired-box-protein, PAX8, isoforms
      generated by alternative splicing in thyroid, kidney and Wilms' tumors.
AB  - The mammalian paired box (Pax) genes encode a family of transcription factors
      involved in embryogenesis. The murine and human Pax8 genes are expressed in
      developing and adult thyroid as well as in the developing secretory system and at
      the lower level in adult kidney. In the secretory system expression is localized
      to the induced, extensively differentiating parts that undergo a transition from
      mesenchyme to epithelium. The human PAX8 gene generates at least five different
      alternatively spliced transcripts encoding different PAX8 isoforms. These
      isoforms differ in their carboxy-terminal regions downstream of the paired domain
      that has been shown previously to be responsible for the DNA binding. The PAX8a
      isoform contains a 63 amino-acid serine-rich region that is absent in the isoform
      PAX8b whereas PAX8c reveals a novel 99-amino-acid proline-rich region. This
      proline-rich region arises due to an unusual reading-frame shift in the PAX8
      transcript. RNAse protection and RT(reverse transcription)-PCR analysis show the
      expression of all three PAX8 transcripts in human thyroid, kidney and five Wilms'
      tumors. Band-shift assay indicates a greatly reduced binding affinity of the
      isoform PAX8c to a DNA sequence from the promoter of the thyroperoxidase gene
      compared to the binding of PAX8a and PAX8b to this sequence. Deletion analysis of
      murine PAX8a indicates that its activating domain residues at the carboxy
      terminus of the protein which is shared by isoforms PAX8a and PAX8b. In
      accordance with these data PAX8a and PAX8b activate transcription from a
      thyroglobulin promoter as well as from a cotransfected synthetic PAX8-specific
      promoter/chlorampericol acetyltransferase (CAT) reporter containing a Pax8
      binding oligonucleotide in front of the basal herpes simplex virus thymidine
      kinase (HSV-TK) promoter (P11/12-TK-CAT). However if the basal HSV-TK promoter of
      this reporter is substituted by a minimal adenovirus E1b TATA element, PAX8a and
      PAX8b fail to activate transcription. Of the three chimaeric forms containing the
      GAL4 DNA-binding domain at the amino-terminal end fused to the corresponding
      carboxy-terminal regions of the PAX8 isoforms beginning immediately downstream of
      the paired domain only a GAL4-PAX8b fusion significantly activates transcription
      from a cotransfected GAL4-specific upstream-activating-sequence (UAS)-TK-CAT
      reporter. Substitution of the basal HSV-TK promoter in this reporter by the
      minimal E1b TATA element does not affect this activation. These results indicate
      that the PAX8 isoforms display different functional properties and may also
      function differently in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7737194
TI  - Kinetic analysis of triple-helix formation by pyrimidine oligodeoxynucleotides
      and duplex DNA.
AB  - The kinetics of triple-helix formation by the pyrimidine oligonucleotide
      d(CTTTCCTTCTTCTTTCCC) (TFO) and the homopurine.homopyrimidine (R.Y) duplex, whose
      purine strand is d(TGAAAAAGAAAGGAAGAAAGGG), (D), was studied using ultraviolet
      absorbance decay measurements, in 50 mM Tris/acetate, pH 6, 50 mM NaCl, 10 mM
      MgCl2. The decay curves were obtained by a static method, measuring as a function
      of time the hypochromicity at 270 nm produced by D and TFO after mixing under
      conditions favorable for triplex formation. This approach allowed direct
      measurement of triplex formation as it proceeded. The kinetic experiments were
      carried out at temperatures below the tm of the triplex, i.e. at 17-33 degrees C,
      and at two different D:TFO ratios, 1:1 and 1:10. When D and TFO were mixed in
      equimolar amounts, 1.7 microM each, the kinetics of triplex formation were
      characterized by half-decay times, t1/2, of 150-390 s. By contrast, when TFO was
      in tenfold excess [14 (mumol TFO).l-1] over D [1.4 (mumol D).l-1], the kinetics
      were faster and the t1/2 decreased to 19-26 s. Different rate equations have been
      used to describe the kinetics of triplex formation under these two different
      conditions. Both sets of experiments provided second-order rate constants, k1, of
      approximately 10(3) l.(mol TFO)-1.s-1 which showed a slight decrease with
      temperature. The rate of triplex formation appeared to be about three order of
      magnitude slower than the rate of duplex recombination, whose rate constant is in
      the order of 10(6) l.(mol oligomer)-1.s-1 [Craig, M. E., Crother, D. M. & Doty,
      P. (1971) J. Mol. Biol. 62, 383-401; Porschke, D. & Eigen, M. (1971) J. Mol.
      Biol. 62, 361-381; Nelson, J. W. & Tinoco, I, Jr (1982) Biochemistry 21, 5289
      5295]. The apparent activation energy associated with the rate constants of
      triplex formation was small and negative (E1 = -26 +/- 15 kJ/mol). The first
      order rate constants of triplex dissociation, k-1, strongly dependent on
      temperature and were in the range 10(-7) s-1 (at 20 degrees C) to 10(-5) s-1 (at
      33 degrees C), with an apparent activation energy that was large and positive (E
      1 = 355 +/- 33 kJ/mol). The rate of triplex formation also showed a significant
      dependence on the ionic strength (I) of the buffer solution. A decrease of I from
      130 M to 57 M resulted in a sixfold decrease of the association constant, from
      2.16 x 10(3) to 0.36 x 10(3) l.(mol TFO)-1.s-1, at 22.5 degrees C.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7737195
TI  - Cloning, sequence analysis and expression of the cDNA encoding a sodium-dependent
      phosphate transporter from the bovine renal epithelial cell line NBL-1.
AB  - We have isolated a full-length cDNA clone of 2.2 kb from a lambda ZapII NBL-1
      (bovine renal epithelial cell) cDNA library using a portion of the rat renal
      sodium-dependent phosphate transporter cDNA as a probe. Expression of this cDNA
      clone in the COS cell line has shown it to specifically encode a sodium-dependent
      phosphate transporter from bovine renal epithelial cells. Sequence analysis of
      the clone showed a single open reading frame of 693 amino acids which has 70%
      similarity to the phosphate transporter of rat and human kidney [Magagnin, S.,
      Werner, A., Markovich, D., Sorribas, V., Stange, G., Biber, J. & Murer, H. (1993)
      Proc. Natl Acad. Sci. USA 90, 5979-5983]. Hydropathy plots of the derived amino
      acid sequence show at least eight possible transmembrane regions, again in
      agreement with data for the rat and human transporters. The sequence contains
      nine putative N-glycosylation sites and nine potential sites for protein kinase C
      phosphorylation. Previously we have shown that the kinetics of phosphate
      transport into NBL-1 cells are significantly different to those for opossum
      kidney cells or rat kidney [Helps, C. & McGivan, J. (1991) Eur. J. Biochem. 200,
      797-803]. This difference is presumably related to differences in the amino acid
      sequence between this protein and other cloned phosphate transporters.

PMID- 7737196
TI  - Purification and partial characterization of the erythrocyte Kx protein deficient
      in McLeod patients.
AB  - A 37-kDa protein was immunopurified from human erythrocytes as a complex with a
      monoclonal antibody directed against the Kell blood group protein of 93 kDa. A
      rabbit antibody raised against the purified complex reacted on a Western blot
      with the 93-kDa and 37-kDa proteins and was able to immunoprecipitate the 37-kDa
      component from K0 erythrocytes which express large amount of the Kx antigen, but
      not from erythrocytes of patients suffering from McLeod syndrome, a X-linked
      disorder in which the Kx antigen is lacking. Additional studies have shown that
      the 37-kDa protein is not glycosylated, and permitted the sequence of the 22
      first N-terminal amino acids to be established. This sequence was identical to
      the predicted protein product of the XK gene cloned recently, which is deleted or
      mutated in McLeod patients [Ho, M., Chelly, J., Carter, N., Danek, A., Crocker,
      P. & Monaco, A. P. (1994) Cell 77, 869-880]. Our findings provide strong evidence
      that the 37-kDa red cell membrane protein is identical to the Kx protein produced
      by the XK structural gene and demonstrate that Kx and Kell proteins are two
      subunits expressed as a complex hold by disulfide bond(s) at the red cell
      surface.

PMID- 7737197
TI  - Ribosome-inactivating proteins (RNA N-glycosidases) from the seeds of Saponaria
      ocymoides and Vaccaria pyramidata.
AB  - From the seeds of the Caryophyllaceae Saponaria ocymoides and Vaccaria pyramidata
      two proteins were purified which have the properties of the type-1 (single-chain)
      ribosome-inactivating proteins [reviewed by Barbieri, L., Battelli, M. G. &
      Stirpe, F. (1993) Ribosome-inactivating proteins from plants, Biochim. Biophys.
      Acta 1154, 237-282]. The proteins have molecular masses of 30.2 kDa (S.
      ocymoides) and 28.0 kDa (V. pyramidata) and pI greater than 9.5, their N-terminal
      amino acid sequences are similar to those of saporin-S6 and dianthin 30, ribosome
      inactivating proteins from other Caryophyllaceae, and they partially cross-react
      with sera against these proteins. Both proteins inhibit protein synthesis by a
      rabbit-reticulocyte lysate with IC50 (concentrations giving 50% inhibition) below
      10(-10) M, have a smaller effect on poly(U)-directed phenylalanine polymerisation
      by rat liver ribosomes (nanomolar IC50, approximately) and on protein synthesis
      by various cell lines (IC50 ranging from 4 nM to > 3000 nM) and possess rRNA N
      glycosidase activity, releasing 1 mol adenine/ribosome.

PMID- 7737198
TI  - PMAP-37, a novel antibacterial peptide from pig myeloid cells. cDNA cloning,
      chemical synthesis and activity.
AB  - A molecular biological approach, based on preproregion homology in the precursors
      of several diverse antibacterial peptides, was used to clone a pig bone marrow
      cDNA encoding a novel 167-residue polypeptide. The preproregion of this
      polypeptide is highly similar to corresponding regions in congeners from pig,
      cattle and rabbit. It is followed by a unique, cationic, 37-residue sequence,
      which was predicted to have a high propensity for an alpha-helical conformation.
      A peptide, termed PMAP-37, corresponding to this sequence, was chemically
      synthesized and shown to undergo a transition from a random coil to an ordered,
      mainly helical, conformation on addition of trifluoroethanol. This behaviour is
      typical of an amphipathic alpha helix, a structure common to several membrane
      active, antimicrobial peptides. In vitro experiments showed that PMAP-37 strongly
      inhibits the growth of several strains of Gram-negative and Gram-positive
      bacteria, with minimal inhibitory concentrations ranging over 1-4 microM, and
      permeabilizes the inner membrane of Escherichia coli. Interestingly, the 15-32
      stretch of PMAP-37 show a remarkable similarity to N-terminal stretches in
      cecropins B and A from Drosophila melanogaster and Cecropia hyalophora,
      respectively. This affords an uncommon example of sequence convergence.

PMID- 7737199
TI  - A new class of photoactivatable and cleavable derivatives of neurotoxin II from
      Naja naja oxiana. Synthesis, characterisation, and application for affinity
      labelling of the nicotinic acetylcholine receptor from Torpedo californica.
AB  - A new series of photoactivatable and cleavable derivatives of neurotoxin II from
      the cobra Naja naja oxiana is investigated which can be used for mapping the
      surface topology of the nicotinic acetylcholine receptor from Torpedo electric
      tissue. The preparation and characterisation of five toxin derivatives, each with
      a radioactive 125I-azidosalicylamidoethyl-1,3'-dithiopropyl group in a defined
      position within the primary structure, are described. The photoinduced cross
      linking reaction of the toxin derivatives with membrane-bound receptor is
      investigated. The photoactivatable group located at position K25 reacts almost
      exclusively with the delta subunit of the receptor, whereas the K15 derivative
      reacts with the alpha and beta subunits. The other derivatives did not react with
      the receptor to any significant extent. It is shown that, with respect to the
      receptor subunits, the cross-linking pattern depends on the length and chemical
      nature of the cross-linking group.

PMID- 7737200
TI  - Manganese peroxidase from Phanerochaete chrysosporium. A homology-based molecular
      model.
AB  - A detailed three-dimensional model of manganese peroxidase was constructed using
      lignine peroxidase as the structural scaffold. This is the only protein in the
      peroxidase family except for cytochrome c peroxidase for which a resolved crystal
      structure is available. The model was built using the following procedure: (a)
      structurally preserved regions were derived from similar regions in the sequence
      alignment of the two proteins; (b) non-similar regions were modelled by searching
      a set of resolved protein structures for fragments which fitted in geometrically
      and choosing the best fitting fragment. Side chains were constructed by
      calculating rotamer-rotamer interaction energies and minimizing intramolecular
      energy. Model refinement was performed by molecular mechanics calculation. The
      quality of the model was assessed on the basis of the propensity of the amino
      acids to be inserted into regular secondary-structure elements and to be exposed
      to solvent. All the lignine peroxidase regions not used for model construction
      because of the lack of similarity, except the helix fragment Leu261-Phe269,
      correspond to external loops, suggesting reliable modelling. The manganese
      peroxidase model structure was analyzed in detail and several functionally
      relevant structural features were predicted, the most important being: (a) the
      very close structural similarity between lignine and manganese peroxidase active
      sites, suggesting a similar mode of hydrogen peroxide activation; (b) the
      substitution of polar residues for the hydrophobic amino acids exposed at the
      edge of the channel involved in substrate recognition in lignine peroxidase,
      suggesting that manganese peroxidase does not directly bind aromatic substrates;
      (c) the location of residues potentially able to bind Mn2+, spatially positioned
      on the side of the 3-CH3 heme edge.

PMID- 7737201
TI  - The effects of phosphorylation of cardiac troponin-I on its interactions with
      actin and cardiac troponin-C.
AB  - It is known that the phosphorylation of two serine residues on the NH2-terminal
      extension specific to cardiac troponin-I (Tn-I) modulates the calcium-dependent
      activation of the myofilaments. The process by which this occurs remains an
      unsolved puzzle. We have applied a dissective approach to study the effect of
      this phosphorylation on the interactions between Tn-I and its partner proteins,
      actin and troponin-C (Tn-C). Using N-[14C]ethylmaleimide-labelled Tn-I in
      sedimentation assays with F-actin, we found that the dephosphorylated Tn-I binds
      to F-actin with pronounced positive cooperativity, both in the absence and the
      presence of tropomyosin. Phosphorylation of the protein slightly weakens the
      interaction in the absence of tropomyosin, but the cooperativity remained. In the
      presence of tropomyosin, phosphorylation of the Tn-I also appeared to slightly
      weaken the interaction as well but, more significantly, the cooperativity was
      eliminated. These data can only be explained simply by a cooperative interaction
      between the monomer units in the actin filament. The interactions between cardiac
      Tn-I and Tn-C were studied by labelling the Tn-C with the fluorescent probe
      dansyl aziridine. As expected, the binding of the dephosphorylated Tn-I to Tn-C
      was strengthened by over 20-fold upon the addition of calcium to the assay.
      Phosphorylation of the protein, however, had a dramatic effect on the interaction
      in that it appeared to desensitise the complex to the effect of calcium: the Ka
      values obtained for both interactions (+/- Ca2+) were almost identical. These
      results clearly indicate that the phosphorylation of Tn-I in the cardiac system
      has dramatic effects on the isolated inter-protein interactions. We also discuss
      the possible significance of such an effect on the interactions of the isolated
      proteins in their roles within the intact cardiac regulatory complex.

PMID- 7737202
TI  - Processing and hydrolytic mechanism of the cgkA-encoded kappa-carrageenase of
      Alteromonas carrageenovora.
AB  - The cgkA gene of Alteromonas carrageenovora encodes a kappa-carrageenase with a
      predicted mass of 44212 Da, much larger than the 35 kDa estimated from SDS/PAGE
      of the protein purified from culture supernatants. Immunoblotting experiments
      showed the presence of a protein of 44 +/- 2 kDa in both native and recombinant
      bacterial intracellular extracts, suggesting that the kappa-carrageenase is
      produced as a preproprotein which undergoes proteolytic processing twice during
      secretion. To determine the exact site of C-terminal cleavage, the precise mass
      of the purified extracellular kappa-carrageenase was measured by electrospray
      ionization/mass spectrometry and found to be 31,741 +/- 3 Da. The mature kappa
      carrageenase of A. carrageenovora thus appears to be composed of 275 amino acids,
      from residue Ala26 to residue Asn301 of the cgkA gene product. To assess the
      molecular mechanism of this member of family 16 of glycosyl hydrolases,
      hydrolysis of neocarrahexaitol by the kappa-carrageenase was monitored by gel
      filtration chromatography and 13C-NMR. Results show that neocarrabiitol and beta
      neocarratetraose are initially formed, demonstrating that the enzyme operates
      with a molecular mechanism retaining the anomeric configuration. Consistent with
      this result, the enzyme was also shown to be able to catalyze transglycosylation.

PMID- 7737203
TI  - Partial purification and characterization of RNase P from Dictyostelium
      discoideum.
AB  - Ribonuclease P (RNase P) from Dictyostelium discoideum has been purified 470
      fold. D. discoideum RNase P cleaves the precursor to Schizosaccharomyces pombe
      suppressor tRNA(Ser) at the same site as S. pombe RNase P, producing the mature
      5' end of tRNA(Ser). pH and temperature optima for enzyme activity are 7.6 and 37
      degrees C, respectively. The enzyme shows optimal activity in the presence of 5
      mM MgCl2 and 10 mM NH4Cl or 5 mM KCl. The apparent Km for the S. pombe tRNA
      precursor derived from the supS1 tRNA(Ser) gene is 240 nM, and the apparent Vmax
      is 3.6 pmol/min. Inhibition of D. discoideum RNase P by proteinase K and
      micrococcal nuclease strongly indicates that the activity requires both protein
      and RNA components. In cesium sulfate density gradients, the enzyme has a buoyant
      density of 1.23 g/ml, indicating a low RNA/protein ratio for the holoenzyme.

PMID- 7737204
TI  - Structural analysis of the sialylated N- and O-linked carbohydrate chains of
      recombinant human erythropoietin expressed in Chinese hamster ovary cells.
      Sialylation patterns and branch location of dimeric N-acetyllactosamine units.
AB  - The N-linked carbohydrate chains of recombinant human erythropoietin expressed in
      CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta
      glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by
      gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q,
      HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1.
      The purified sialylated oligosaccharides were analyzed by one-dimensional and two
      dimensional 500-MHz 1H-NMR spectroscopy. When necessary, oligosaccharides were
      treated with endo-beta-galactosidase (and N-acetyl-beta-glucosaminidase) followed
      by 1H-NMR analysis of the incubation products, to obtain additional structural
      information. Di-, tri-, tri'- and tetraantennary N-acetyllactosamine-type
      oligosaccharides occur which can be completely (major) or partially (minor)
      sialylated. Three different types of alpha 2-3-linked sialic acids are present,
      namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N
      acetyl-9-O-acetylneuraminic acid (3%). In the case of partial sialylation, a non
      random distribution of the sialic acids over the branches is observed. One or two
      extra N-acetyllactosamine units, being exclusively located in the branches
      attached to the alpha 1-6-linked Man residue, can be present in completely or
      partially sialylated di-, tri'-, and tetraantennary oligosaccharides.
      Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be
      digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis,
      whereas under the same conditions tri' antennary oligosaccharides hardly reacted
      (< 15%). Using endo-beta-galactosidase from Escherichia freundii, these
      tri'antennary oligosaccharides could be digested more extensively (> 75%). The O
      linked carbohydrate chains were released from the O-glycoprotein by alkaline
      borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb
      NH2. Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and
      Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol.

PMID- 7737205
TI  - Are breathlessness and fatigue in chronic heart failure due to the same
      pathophysiological abnormality?

PMID- 7737206
TI  - Measurement of atrial volumes by magnetic resonance imaging in healthy volunteers
      and in patients with myocardial infarction.
AB  - Magnetic resonance imaging was used to measure atrial volumes and emptying
      fractions in healthy volunteers to establish normal ranges and also in patients
      with myocardial infarction. Fourteen healthy volunteers (age mean +/- SD, 47 +/-
      13 years) and 14 patients (age 56 +/- 9) with previous myocardial infarction were
      studied. All patients were in sinus rhythm, had competent cardiac valves and no
      heart failure. Atrial and ventricular volumes were measured from a set of cardiac
      gated transverse spin echo images (TE 40 ms) covering the heart and acquired at
      the end of ventricular systole and diastole. Ventricular ejection fractions and
      atrial emptying fractions were calculated. In patients with myocardial
      infarction, left atrial end-diastolic and systolic volumes were significantly
      higher (P < 0.001), and the emptying fraction significantly lower (P < 0.001)
      than in the control group. The right atrial end-diastolic volume was also
      significantly higher (P < 0.05) and the emptying fraction significantly lower (P
      < 0.01) than those in the control group. These findings are likely to be due to
      abnormal left ventricular long axis dynamics caused by damage to the myocardium,
      and reflect the abnormal systolic and diastolic functions of the left ventricle
      which contribute to atrial filling and emptying, respectively. Changes in atrial
      volumes can be measured non-invasively by magnetic resonance imaging. Using this
      method we have studied the normal ranges and demonstrated abnormalities in
      patients with myocardial infarction. Thus this imaging method may prove to be
      useful for studying atrial function under different physiological and
      pathological conditions and for evaluating the effect of therapeutic
      interventions on atrial function.

PMID- 7737208
TI  - High incidence of left atrial thrombus detected by transoesophageal
      echocardiography in heart transplant recipients.
AB  - The aim of the study was the detection of spontaneous echo contrast (SEC) and
      left atrial thrombus by transoesophageal echocardiography (TEE) in patients who
      had undergone orthotopic heart transplantation. TEE was prospectively performed
      in 64 heart transplant recipients (53 males, 11 females, mean age 51 years).
      Since surgery (mean time: 31 months), all heart transplant recipients had
      received either aspirin (39), or dipyridamole (22), or both (3). Despite the
      antiplatelet treatment, an acute arterial embolism (two strokes, one popliteal
      and one mesenteric ischaemia) occurred in four patients who subsequently received
      an oral anticoagulant therapy. TEE was performed with a biplane high-frequency
      transducer after lidocaine pharyngeal anaesthesia, midazolam intravenous
      injection and antibiotic prophylaxis. Mean ejection fraction was 63 +/- 10%. None
      had evidence of rejection at endomyocardial biopsy performed on the same day as
      TEE and analysed in a blinded fashion. All were in sinus rhythm. Left atrial SEC
      was found in 35 patients (55%) and was associated with left atrial thrombus in 18
      patients (28%). These thrombi were localized in the donor left atrial appendage
      in 10 cases, on the posterior wall of the left atrium in six cases, on the donor
      part of inter-atrial septum in one case and on the suture line in one case. They
      were not detected by transthoracic echocardiography (TTE). When compared with
      patients without thrombus, no difference was found concerning left atrial size,
      left ventricular ejection fraction, pulmonary artery pressure and number of
      previous episodes of rejection. However, cardiac index was significantly lower in
      patients with left atrial thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737207
TI  - Can intracoronary ultrasound correctly assess the luminal dimensions of coronary
      artery lesions? A comparison with quantitative angiography.
AB  - In 62 patients with angina pectoris Canadian Class III and IV, the luminal
      dimensions of 25 pre-PTCA and 56 post-PTCA lesions without occlusion were
      examined with a 4.3 F 30 MHz mechanical ultrasound imaging catheter, and analysed
      off-line using ultrasound cross-sectional area (U-CSA) measurements from s-VHS
      video images (n = 81). In addition, 42 angiographically normal coronary segments
      were examined. At the site of the examination, the U-CSA was integrated centrally
      to the leading edge echo of the inner contour of the vessel wall and the
      corresponding angiographic cinefilm images were analysed by edge detection using
      the Cardiovascular Angiography Analysis System. The obstruction diameter (at the
      lesion) and the mean vessel diameter (at normal sites) were used to calculate the
      angiographic cross-sectional area (A-CSA) assuming a circular model. U-CSA values
      were compared with the corresponding A-CSA values using t-test and linear
      regression analysis. The study showed that larger CSA are measured with
      ultrasound than with angiography. (P < 0.0001). An acceptable correlation was
      found between U-CSA and A-CSA values in normal coronary segments (correlation
      coefficient: r = 0.73, mean diff. = 1.44 +/- 1.22 mm2). However, the correlation
      was poor at the site of pre-PTCA lesions (r = 0.62, mean diff. = 1.81 +/- 1.14
      mm2) and deteriorated following PTCA (r = 0.47, mean diff. = 1.28 +/- 2.20 mm2).
      No correlation was found between the degree of lumen eccentricity measured with
      intracoronary ultrasound (ICUS) and the individual differences between U-CSA and
      A-CSA values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737209
TI  - New echo-anatomical correlations in aortic dissection.
AB  - Acute dissection of the aorta is a life-threatening condition requiring immediate
      diagnosis and definitive treatment. Transoesophageal echocardiography may be
      considered the diagnostic procedure of choice in the assessment of patients with
      aortic dissection. A detailed morphological and functional study of the aorta
      must be obtained quickly. This report summarizes the echo-anatomical correlation
      of two distinct echocardiographic images of patients with aortic dissection.

PMID- 7737210
TI  - The impact of 'Shahal' (a new cardiac emergency service) on subscribers' requests
      for medical assistance: characteristics and distribution of calls.
AB  - The objectives of this study were to assess the impact of the new 'Shahal' (pre
      hospital cardiac service) on subscribers' 'decision time'. A professional 24-h
      mobile emergency cardiac service has been set up, monitored by intensive care
      nurses via a central computerized operation unit. All subscribers carry a
      cardiobeeper for trans-telephonic transmission of a 3-lead electrocardiogram as
      well as an automatic intramuscular lidocaine injector for self-injection. During
      a 1-year period, data from 10,304 subscribers' charts were reviewed and analysed.
      Seventy-nine percent were cardiac patients and 15% were completely healthy.
      Median decision time for the general population was 44 min (range < 15 min to > 3
      h); 59% of subscribers called within 1 h from onset of symptoms and 29% delayed
      calling for 3 h and more. The healthy subjects alerted the service significantly
      earlier (29 min). Three patterns of behaviour emerged from analysis of the daily
      distribution of calls.

PMID- 7737211
TI  - Coronary artery disease in identical twins.
AB  - Coronary angiography in a pair of identical twins is described. Despite
      similarities in coronary risk factors, major differences were seen in both the
      anatomy and the degree of coronary disease.

PMID- 7737212
TI  - Spontaneous coronary artery dissection during pregnancy and post partum.
AB  - This report describes a 35-year-old 40 week pregnant woman who was hospitalized
      with a diagnosis of acute anteroseptal myocardial infarction. She sustained
      another, infero-posterior, infarction 4 days later. Coronary arteriography
      performed after successful Cesearean section displayed primary dissections of the
      right as well as both left coronary arteries. Her subsequent clinical course was
      uneventful with medical therapy. This patient is the first non-surgically treated
      survivor of peripartal spontaneous coronary artery dissection with a myocardial
      infarction prior to delivery.

PMID- 7737213
TI  - Assessment of non-invasive new imaging techniques in the diagnosis of heart
      liposarcoma.
AB  - Two patients, with recurrent acute pericarditis as the first presentation of
      liposarcoma, were admitted to our department between August and December 1992.
      The pericarditis was pericardial in one case and retroperitoneal with pericardial
      inflammation in the other. In contrast to most reported cases, where diagnosis
      was made post-mortem, diagnosis and surgical decision were based on non-invasive
      imaging techniques, without cardiac angiography. In cases of recurrent acute
      pericarditis resistant to usual drugs, new imaging techniques, such as computed
      tomodensitometry and magnetic resonance imaging, can detect rare causes such as
      liposarcomas in which prognosis is critically dependent on early diagnosis.

PMID- 7737214
TI  - Improving long-term survival of patients with acute myocardial infarction from
      1977-1988 in a region of Denmark.
AB  - The aim of this investigation was to study secular trends in long-term survival
      following myocardial infarction (MI). Five thousand one hundred and fifty-seven
      consecutive cases of MI in 3942 patients were recorded in a well-defined region
      in the study period 1977-1988. The study period ended before thrombolytic therapy
      was introduced in the hospital. One and 5-year survival (+/- 95% confidence
      limits) was 61 +/- 2% and 42 +/- 2% in 1977-1980. These figures changed to 61 +/-
      2% and 44 +/- 2% in 1981-1984, and to 64 +/- 2 and 46 +/- 2% in 1985-1988. The
      improvement with time was statistically significant (P < 0.001). In a Cox
      proportional hazard model, time of infarction was an independent predictor of
      survival. Patients were subdivided into a high risk group suffering from either
      congestive heart failure or cardiac arrest during hospitalization, and a low risk
      group without these complications. Year of infarction was without importance in
      the high risk group but highly significant in the low risk group. Long-term
      survival following MI gradually improved prior to the introduction of
      thrombolytic therapy. The improvement was confined to low risk patients without
      cardiac arrest or congestive heart failure.

PMID- 7737215
TI  - Severe left ventricular dynamic outflow tract gradient secondary to localized
      septal hypertrophy and concomitant acute ischaemic parietal dyssynergy.
AB  - Localized basal septal hypertrophy (LSH) is usually an incidental
      echocardiographic finding and, as opposed to asymmetric hypertrophic
      cardiomyopathy (AHC), is of no clinical significance. We report a case of a
      patient with LSH who developed a severe left ventricular outflow gradient during
      acute myocardial ischaemia, apical akinesis and compensatory hyperkinesis of
      basal parietal segments.

PMID- 7737217
TI  - Coronary intravascular ultrasound--is it coming of age?

PMID- 7737216
TI  - Vectorcardiographic monitoring to assess early vessel patency after reperfusion
      therapy for acute myocardial infarction.
AB  - Reperfusion therapy has lowered mortality in patients suffering from acute
      myocardial infarction. Failure to reperfuse is associated with an increased short
      and long-term mortality. In a prospective study we used dynamic
      vectorcardiography to monitor 96 patients with acute myocardial infarction
      treated with reperfusion therapy to non-invasively assess coronary patency. The
      results from continuous monitoring were compared to those obtained from
      angiography. By using trend-analysis of QRS vector difference and ST vector
      magnitude, we were able to correctly identify 58 of the 70 patients (83%) with a
      reperfused infarct-related artery, and 19 of the 26 patients (73%) with a
      persistently occluded artery demonstrated at an early angiogram (diagnostic
      accuracy 80%). In patients with high-grade collateral flow to the infarct-related
      area, the results of the vectorcardiographic monitoring and of angiography showed
      the largest disagreement, whereas the accuracy of vectorcardiographic monitoring
      was high: 88% among patients without collaterals. The present results suggest
      that QRS complex and ST segment vectorcardiographic monitoring is a useful tool
      for assessing early coronary artery patency, and that dynamic vectorcardiography
      may help in identifying candidates for emergency coronary angiography.

PMID- 7737218
TI  - Long-term risk factors from non-invasive evaluation of patients with acute chest
      pain, but without myocardial infarction.
AB  - The aims were to identify long-term risk factors for cardiac events, i.e. cardiac
      death and non-fatal acute myocardial infarction (AMI), and for development of
      angina pectoris among patients admitted with acute chest pain, but without
      confirmed AMI (non-AMI). A total of 257 consecutive non-AMI patients without
      other severe disease and below 76 years of age were included. Medical history and
      variables from the ECG while exercising, thallium scintigrams, Holter-monitoring,
      echocardiography and chest X-ray were recorded. The patients were followed for 7
      years regarding cardiac death, non-fatal AMI and development of angina pectoris.
      The variables recorded at admission were compared to follow-up results by means
      of Uni- and multivariate analyses. During follow-up, 69 cardiac events, 44
      cardiac deaths and 25 non-fatal AMIs occurred. The following variables provided
      independent prognostic information (relative risk factors with 95% confidence
      limits in brackets): age (1.05, 1.01-1.09), abnormal ECG at rest (2.81, 1.33
      5.90), low increase in rate pressure product (4.57, 2.21-9.44), multiform
      premature ventricular beats (VPB) (2.61, 1.34-5.09) and transient thallium
      defects (2.64, 1.33-5.24). Sub-analysis of patients with and without a history of
      coronary artery disease (CAD) prior to admission identified the following risk
      factors: (1) Patients with previous CAD: abnormal ECG on admission, low increase
      in rate pressure product, ST depression during exercise. (2) Patients without
      previous CAD: abnormal ECG at rest, multiform VPBs and low increase in rate
      pressure product. Development of angina pectoris during follow-up of patients
      without previous CAD could not be predicted by any of the variables.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7737219
TI  - D-dimer and fibrinolysis in patients with various degrees of atherosclerosis.
AB  - D-dimer, plasminogen activator inhibitor (PAI-1) activity at rest and after
      exercise, and tissue plasminogen activator (t-PA) activity after exercise were
      measured in venous blood in 88 patients with atherosclerotic lesions of various
      degrees. According to clinical symptoms, coronary angiography (CAG), ultrasound
      Doppler signal and duplex and colour Doppler scanning of carotid arteries and
      their branches, subclavian, vertebral and peripheral arteries of the lower limbs,
      patients were divided into four groups. Group 1, 16 men without CAG and
      ultrasound signs of atherosclerotic lesions; group 2, 27 patients with CAG
      confirmed coronary artery disease; group 3, 18 patients with peripheral artery
      occlusive disease; group 4, 27 patients with coexistence of two or more regions
      of atherosclerotic lesions. D-dimer was the highest in patients with the most
      extensive atherosclerosis: 432 +/- 164 ng.ml-1 in group 3, 429 +/- 98 ng.ml-1 in
      group 4 vs 163 +/- 25 ng.ml-1 in group 1, P < 0.05. There were correlations (P <
      0.05) between: age and D-dimer (r = 0.29); D-dimer and t-PA (r = 0.34); D-dimer
      and PAI-1, r = -0.29. Patients were also analysed according to D-dimer level. In
      patients with the highest level of D-dimer, the lowest level of PAI-1 activity
      and the highest level of t-PA activity after exercise were observed. The low PAI
      1 activity is probably the result of an increased release of t-PA in these
      patients.

PMID- 7737220
TI  - Mitral valve rupture following percutaneous mitral commissurotomy: existence of
      predictive factors.
AB  - The purpose of this study was to describe the mechanism and determine predictive
      factors of mitral valve rupture requiring valve replacement following
      percutaneous mitral commissurotomy. Of the 350 consecutive patients treated by
      balloon mitral commissurotomy, the procedure was not completed in 16, and 11
      developed acute severe mitral regurgitation requiring valve replacement: seven
      cases of anterior leaflet rupture, three cases of posterior leaflet rupture and
      one case of anterior chordal surface. These 27 group I patients were compared to
      the remaining 323 (group II) in whom the procedure was completed. The 11 excised
      valves were evaluated by an experienced pathologist. Eight of the 11 patients had
      an echocardiographic score < 8 (mean score 6.5 +/- 1), no valvular calcification
      at X-ray and double balloon percutaneous mitral commissurotomy. Microscopy in six
      patients showed focal fibrous thickening at the site of the rupture but no
      calcification. One patient developed severe mitral regurgitation due to chordal
      rupture with an Inoue balloon. The two remaining patients had an echo score of
      ten and valve calcification on X-ray. Microscopy revealed severe homogeneous
      chronic rheumatic mitral disease. In one of these two patients, leaflet rupture
      was related to an 'oversized balloon' (2 x 19 mm + 15 mm). Statistical analysis
      showed only echo score differences between the two groups (6.9 +/- 1.4 in group I
      vs 8.2 +/- 1.6 in group II, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737221
TI  - Muscle fatigue and dyspnoea in chronic heart failure: two sides of the same coin?
AB  - The pathogenesis of the limiting symptoms in patients with chronic heart failure,
      shortness of breath and fatigue on exercise, are poorly understood. We analysed
      data from 222 incremental symptom limited exercise tests to determine whether
      there were differences between patients stopped by breathlessness or fatigue. One
      hundred and sixty patients were stopped by breathlessness and 62 by fatigue.
      There was no differences between the two groups in underlying diagnosis or in
      exercise performance (peak oxygen consumption 15.66 (+/- 5.62) ml.kg-1.min-1 in
      the fatigue group, 15.13 (+/- 4.64) in the breathless group). The ventilatory
      response as assessed by ventilatory response to carbon dioxide production
      (VE/VCO2 slope) was not different between the two groups (2.61 (+/- 0.96) in the
      fatigue group, 3.03 (+/- 1.23) in the breathless group: P = ns). There were no
      differences between the two groups in left ventricular dimensions, left
      ventricular ejection fraction or left ventricular end-diastolic pressure. The
      limiting symptoms of breathlessness and fatigue in chronic heart failure are two
      sides of the same coin. Any pathophysiological explanation of exercise limitation
      in chronic heart failure must unify these two symptoms.

PMID- 7737223
TI  - Idiopathic dilated cardiomyopathy among Swedish patients with congestive heart
      failure.
AB  - Idiopathic dilated cardiomyopathy (IDCM) is an exclusion diagnosis. Although it
      is a prognostically important entity and a common indication for cardiac
      transplantation, the incidence and age distribution of idiopathic IDCM in a well
      defined population today is unknown. The present study intended to estimate the
      proportion of IDCM among congestive heart failure (CHF) patients, and to evaluate
      its prognostic implications. The records of all 16-65-year-old patients
      hospitalized for CHF or IDCM during a 6-year period (n = 2711) were evaluated in
      a defined region of Western Sweden (1.05 million inhabitants 16-65 years of age).
      Twenty-two percent (584/2711) of these records contained no plausible cause of
      CHF or IDCM, and among living patients an obvious aetiology was lacking in 27%
      (411/1516). These 411 patients were subsequently offered a diagnostic
      investigation including echocardiography, and were compared to a randomly
      selected healthy control group (n = 103). Of 411 patients, 293 accepted the
      investigation and 286 had acceptable echocardiographic recordings, indicating
      left ventricular dilatation and systolic dysfunction in 30%. From the hospital
      records, 170 patients were identified as new cases of IDCM during the 6-year
      period. Adding another 34 cases revealed by our diagnostic procedures yielded an
      age-gender standardized incidence rate of 29.2 cases per 10(6) persons/year. The
      incidence of IDCM increased considerably with age, although in younger patients
      its relative contribution to heart failure was greater. The incidence of IDCM was
      higher in the urban compared to the rural parts of the region 21 vs 32/10(6); P =
      0.013). The estimated prevalence was 131/10(6).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737222
TI  - Fibrates and statins in the treatment of hyperlipidaemia: an appraisal of their
      efficacy and safety.

PMID- 7737224
TI  - Left ventricular diastolic function in asymptomatic and symptomatic human
      immunodeficiency virus carriers: an echocardiographic study.
AB  - Acquired immunodeficiency syndrome (AIDS) is a systemic illness affecting
      multiple organs, including the heart. Left ventricular (LV) diastolic dysfunction
      has been reported as the first echocardiographically detectable abnormality in
      several cardiovascular disorders. We tested the hypothesis that Human
      Immunodeficiency Virus (HIV) carriers have LV diastolic impairment when studied
      early in the clinical course of the infection. Doppler echocardiographic and
      computerized time-motion parameters of LV diastolic function were obtained in 51
      HIV patients and in 25 age- and sex-matched healthy controls. The HIV population
      consisted of 28 totally asymptomatic subjects and 23 patients with incipient
      AIDS. As compared to controls, the HIV group had similar heart rate, blood
      pressure level, LV dimensions and fractional shortening, but increased
      isovolumetric relaxation time (P = 0.03), early filling duration (P < 0.001) and
      decreased early mitral flow peak velocity (E) (P = 0.02) and EF slope (P <
      0.001). HIV patients also showed lower values for posterior wall thinning (PWT, P
      < 0.01) and peak lengthening velocity of the posterior wall (PVL, P < 0.05), and
      a trend to a decreased peak rate of LV enlargement in diastole (D+, P = 0.05).
      Doppler-derived parameters of diastolic function were significantly altered in
      the asymptomatic HIV group vs controls. The LV diastolic indices were similar in
      symptomatic and asymptomatic HIV patients except for PWT, which was lower in the
      symptomatic HIV group (P = 0.04). Since mild and focal wall motion abnormalities
      were detected in 11 HIV carriers (22%), comparison of LV diastolic indexes
      between HIV patients and controls was also performed in two subgroups; these
      included asymptomatic (n = 26) and symptomatic (n = 14) patients with normal
      contractile state. The two subgroups had abnormalities of diastolic function
      similar to those of the HIV group as a whole, but with somewhat lower levels of
      statistical significance. Our data strongly suggest that there is myocardial
      involvement at the early stage of HIV infection; however, its impact on the
      clinical course of the disease remains to be clarified.

PMID- 7737225
TI  - The dispersion of repolarization in patients with ventricular tachycardia. A
      study using simultaneous monophasic action potential recordings from two sites in
      the right ventricle.
AB  - The role of increased dispersion of repolarization in the genesis of torsade de
      pointes and ventricular fibrillation has been well recognized generally, but not
      in the genesis of monomorphic ventricular tachycardia (VT). Monophasic action
      potentials (MAP) were therefore recorded simultaneously from the right
      ventricular (RV) apex (RVA) and outflow tract (RVOT) during sinus rhythm, RV
      pacing and programmed extra stimulation (PES) in 24 patients with VT. The
      activation time (AT), MAP duration at 90% repolarization (MAPd), and
      repolarization time (RT) were measured and their dispersions, defined as the
      differences in these parameters between RVA and RVOT, were calculated. During
      sinus rhythm and RV pacing, the dispersions of AT, MAPd and RT (dispersions) were
      significantly larger in the 17 patients with a VT induced than in those without.
      During PES, the dispersions were further augmented in the S2 beats in the seven
      patients with a sustained VT induced, the maximal dispersion of RT being 85 +/-
      22 ms. Both the dispersion of AT and that of MAPd contributed to the dispersion
      of RT. In both of our two patients with a sustained VT induced during MAP
      recording, a marked increase in dispersions of RT (140 and 190 ms, respectively)
      was observed immediately before the initiation of the VT. A link between the
      dispersions and the inducibility of a monomorphic VT was found in our patients,
      which suggests that the increased dispersions play an important role in the
      genesis of a monomorphic VT.

PMID- 7737226
TI  - Risk factors of cardiac arrest in arrhythmogenic right ventricular dysplasia.
AB  - Arrhythmogenic right ventricular dysplasia is an important cause of ventricular
      arrhythmia with a potential risk of sudden cardiac death in a young population.
      In order to define risk factors of cardiac arrest, angiographic and
      electrophysiological data from 60 patients with angiographically documented
      arrhythmogenic right ventricular dysplasia (of whom 20 also had spontaneous non
      sustained ventricular arrhythmias, 27 sustained ventricular tachycardia and 13
      suffered cardiac arrest with documented ventricular fibrillation before
      resuscitation) were analysed. There were no statistically significant differences
      in right ventricular volume, global right ventricular ejection fraction (RVEF),
      right ventricular structure, mean age at the time of diagnosis and angiographic
      left ventricular contraction abnormalities in the subgroups of patients with
      different forms of spontaneous arrhythmias. Only in a subgroup of patients with
      cardiac arrest and inducible sustained ventricular tachycardia did right
      ventricular volume (P < 0.05), ejection fraction (P < 0.001) and the amount of
      structural changes (P < 0.01) reveal significant results. A subgroup of patients
      with structural alterations and a low level of right ventricular function is at a
      high risk of cardiac arrest, although strenuous exercise and sport remain most
      important risk factors.

PMID- 7737227
TI  - Rapid intravenous infusion of d-1 sotalol: time to onset of effects on
      ventricular refractoriness, and safety.
AB  - d-1 sotalol is one of the most effective antiarrhythmic agents currently
      available for ventricular tachyarrhythmias, but the recommended infusion rate of
      10-20 min is too slow for rapid pharmacological termination of sustained
      ventricular tachycardia (VT) or for use during cardiac arrest. The safety of the
      drug and time lag from its rapid administration to onset of significant effects
      on ventricular refractoriness is unknown. One hundred and nine patients with a
      history of spontaneous and inducible sustained ventricular tachyarrhythmias were
      studied. d-1 sotalol (1.5 mg.kg-1) was infused over 5 min in the first 57
      patients (mean age 61 +/- 13 years, mean ejection fraction 37 +/- 15%, range 15
      70%). d-1 sotalol was then given over 1 min in the next 52 patients (mean age 61
      +/- 12 years, mean ejection fraction 35 +/- 11%, range 18-58%). The time course
      of change in right ventricular effective refractory period (RVERP) was measured
      in 15 consecutive patients following the 5 min infusion and in all 52 patients
      following the bolus injection. Following the 5 min infusion, RVERP increased
      rapidly from a baseline of 231 +/- 17 ms, reaching a plateau of 268 +/- 23 ms at
      10 min. Following the 1 min injection, RVERP increased virtually immediately from
      a baseline of 237 +/- 25 ms to reach a plateau of 271 +/- 31 ms at 5 min. Two
      patients (one in each group) developed symptomatic hypotension; both responded to
      volume replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737229
TI  - Left ventricular diastolic parameters in 288 normal subjects from 20 to 80 years
      old.
AB  - Left ventricular diastolic indexes are influenced by several variables. In order
      to evaluate the relationship of these indexes to age, heart rate, sex and to
      standard echo parameters, 288 normal subjects aged from 20 to 80 years, divided
      into six age groups, underwent a two-dimensional colour Doppler examination.
      Doppler examination was performed from the apical four chamber view to evaluate
      transmitral flow; isovolumic relaxation time (IVRT) was measured from an apical
      five chamber view. In order to obtain a sufficient number of subjects for an
      adequate statistical analysis, seven hospitals were involved in the study.
      Univariate analysis showed that age influences the peak velocity of the E (r = 
      0.46) and A waves (r = 0.46), the E/A ratio (peak velocities) (r = -0.69), the A
      wave integral (r = 0.48) and the E/A integral ratio (r = -0.57), the early and
      late filling fractions (r = -0.48 and r = 0.51 respectively), and the E wave
      deceleration (r = -0.43) and deceleration time (r = 0.36). In subjects older than
      70 years an inversion of the E/A wave ratio was observed. Multivariate analysis
      confirmed that age has an important influence on left ventricular diastolic
      indexes but also demonstrated that heart rate has a significant influence. Sex,
      ejection fraction (EF), and the dimensions of the mitral annulus and the left
      ventricular posterior wall had less influence on left ventricular diastolic
      indexes. The mean values of E and A wave acceleration, deceleration and peak
      velocity were used to depict left ventricular filling morphology in various age
      groups for three different heart rate values. The conclusions of the study, are:
      (1) normal left ventricular diastolic parameters were obtained as mean values at
      seven different hospitals (2) when evaluating left ventricular diastolic function
      parameters it is important to take into account age and heart rate; E/A inversion
      in older subjects should be considered the normal mitral flow pattern.

PMID- 7737228
TI  - Effect of peri-operative diltiazem on myocardial ischaemia and function in
      patients receiving mammary artery grafts.
AB  - A prospective, randomized study was performed with 66 patients undergoing
      elective coronary bypass surgery involving internal mammary artery (IMA) grafts
      to the left anterior descending artery (LAD). Patients received a continuous peri
      operative infusion of either diltiazem (0.1 mg.kg-1 h-1, n = 32) or nitroglycerin
      (1 microgram.kg-1 min-1, n = 34) for 24 h. The aim of this study was to define
      the effect of the calcium channel blocker diltiazem on peri-operative ischaemia,
      arrhythmias and myocardial function in patients receiving arterial bypass grafts
      by preventing transient vasospasm. The study patients did not differ with respect
      to pre-operative, operative and haemodynamic data. Patients treated with
      diltiazem had lower numbers of ventricular premature beats/hour (8.1 +/- 7.8 vs
      20.5 +/- 11.2; P < 0.05). The anti-ischaemic efficacy of peri-operative diltiazem
      in patients receiving IMA grafts significantly reduced the incidence and duration
      of transient ischaemic events (0 vs 5). Additionally, patients receiving IMA
      grafts and diltiazem showed significantly lower peak levels of ischaemia
      sensitive laboratory parameters, as compared to IMA graft patients receiving only
      nitroglycerin: CK-MB: 17.3 +/- 7.7 vs 23.5 +/- 11.0, (P < 0.05); MB-M: 29.4 +/-
      14.7 vs 43.1 +/- 27.4, (P < 0.05); troponin-T: 0.88 +/- 0.6 vs 1.41 +/- 0.9, (P <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737231
TI  - Metabolism of 4-(3-cyclohexylpropionyl)-1-(2-ethoxyphenyl) piperazine (D-16120)
      by rat liver microsomes.
AB  - The metabolic fate of central analgesic 4-(3-cyclohexylpropionyl)-1-(2
      ethoxyphenyl) piperazine (D-16120), was studied in vitro with phenobarbital 3
      methylcholanthrene and clofibrate induced rat liver microsomal fractions. The
      presence of four metabolites was directly or indirectly established.
      Biotransformation products were isolated by TLC and HPLC techniques and, when
      possible, the structures were confirmed through comparison with synthetic
      samples. The metabolic pathways involved are oxidative dealkylation, aromatic and
      alicyclic hydroxylation.

PMID- 7737230
TI  - Improvement of the diuretic effect of triamterene via solid dispersion technique
      with PEG 4000.
AB  - The present investigation was designed and undertaken in order to substantiate
      further contention concerning the universality of the utilization of PEG polymers
      as matrix carriers. This study could then be considered an attempt to enhance the
      dissolution rate of triamterene, with the subsequent enhancement in its
      absorption rate, via solid dispersion using PEG 4000. The approach of solid
      dispersions was found useful for optimizing the pharmacokinetic of triamterene in
      rats.

PMID- 7737232
TI  - Influence of rifampicin on the toxicity and the analgesic effect of
      acetaminophen.
AB  - The influence of rifampicin on the toxicity, analgesic effect and
      pharmacokinetics of acetaminophen was studied in male albino mice. Repeated
      administration of rifampicin (50 mg/kg i.p. daily for 6 days) shortened
      hexobarbital sleeping time and increased liver weight, microsomal cytochrome P
      450 and heme contents, NADPH-cytochrome c reductase and ethylmorphine-N
      demethylase activities. Aniline hydroxylase activity was decreased and
      glucuronidation of p-nitrophenol was unaffected. Rifampicin pretreatment changed
      neither the LD50 of acetaminophen nor the hepatic glutathione level nor the
      glutathione depletion provoked by the toxic dose of acetaminophen (737 mg/kg
      p.o.). This suggests that rifampicin has no influence on the amount of
      acetaminophen toxic metabolites formed in the liver. Rifampicin decreased the
      acetaminophen analgesic effect in mice. Rifampicin decreased the Cmax, the half
      time, the MRT and the AUC of acetaminophen and accelerated its clearance. The
      plasma concentration of acetaminophen glucuronide and acetaminophen sulfate was
      increased. It is assumed that the most probable mechanism by which rifampicin
      decreases acetaminophen analgesia is the accelerated acetaminophen elimination.

PMID- 7737235
TI  - Antibiotic activity in serum following single and repeated oral administration of
      sodium fusidate in volunteers.
AB  - The pharmacokinetics of antibiotic activity were investigated in 10 healthy,
      female volunteers receiving a single oral dose of sodium fusidate (500 mg)
      followed after 48 h by repeated oral dosing of 250 mg b.i.d. for 5 consecutive
      days. By use of turbidimetry, drug-related antibiotic activity in serum was
      determined and expressed as fusidic acid equivalents. After a single dose and
      repeated dosing, the peak concentrations were (mean +/- SE): 30 +/- 3
      micrograms/ml and 27 +/- 3 micrograms/ml, respectively (NS), and the trough
      concentration at steady state was 8.4 +/- 1.8 micrograms/ml. The experimental and
      predicted accumulation ratios were 2.1 +/- 0.1 versus 1.6 +/- 0.2, respectively
      (P < 0.16). By use of a model independent method, the terminal elimination half
      lives were estimated to be 11 +/- 1 h and 13 +/- 2 h after a single dose and
      repeated doses, respectively (NS). The total clearances of antibiotic activity
      were 2.0 +/- 0.4 l/h after a single dose and 1.6 +/- 0.2 l/h after repeated doses
      (P < 0.11). Model dependent pharmacokinetic parameters were also obtained by
      fitting a two-compartment open model to the median serum concentrations which,
      with respect to half-life and clearance, gave values close to those observed by
      use of the model independent approach. Safety-wise, biochemical parameters were
      within the normal range. However, a statistically significant increase in ASAT
      and a decrease in leucocytes were observed. The tolerability of the drug was good
      and only minor adverse events were reported.

PMID- 7737234
TI  - A comparative study of uranyl nitrate and cisplatin-induced renal failure in rat.
AB  - Renal dysfunction can have substantial effects on the pharmacokinetics and
      pharmacodynamics of drugs. A wide variety of animal models have been developed in
      an attempt to mimic conditions seen in human renal failure. In reality, no single
      animal model would be completely satisfactory because the etiology and
      development of renal failure are diverse. During recent years injection of uranyl
      nitrate has been found to be the most effective and easiest method to produce
      renal dysfunction in laboratory animals. Changes over the last 10 years in
      government regulations on the production and use of radioactive substances make
      the compound less available. There is, therefore, a need for a more accessible
      compound comparable to uranyl nitrate as an inducer of renal failure. The present
      study compares the effects of another known nephrotoxin, cisplatin, with uranyl
      nitrate in the rat. Cisplatin was chosen because of its ability to produce kidney
      damage and its identical site and mechanism of action on the kidneys as uranyl
      nitrate. In the present study, rats were given different i.v. doses of uranyl
      nitrate or cisplatin dissolved in 0.9% of saline solution. The effects of
      nephrotoxins were evaluated on the basis of changes in body weight, creatinine
      and blood urea nitrogen (BUN) concentrations. It was found that the degree of
      renal damage produced by uranyl nitrate and cisplatin is a function of the
      administered dose. With increasing dose there is evidence of more severe kidney
      damage, as measured by substantially increased plasma concentrations of
      creatinine and BUN. The time required to return to normal creatinine and BUN
      concentrations was also a function of dose. Furthermore, plasma alanine
      aminotransferase (ALT) activity was measured as an index of hepatocellular
      damage. The ALT test showed that a single dose does not affect the liver
      function. From dose-response curves a dose of 4 mg/kg body weight of uranyl
      nitrate or cisplatin was chosen to produce acute renal failure in animals for
      pharmacokinetic study of barbital. Barbital (100 mg/kg) was administered on the
      fifth day (the day of maximum renal dysfunction) to uranyl nitrate, cisplatin
      treated and control rats. The elimination rate constant (k), elimination half
      life (t1/2), volume of distribution at steady state (Vss), total (CLt) and renal
      clearance (CLr) were significantly different in treated groups of rats from
      control, however no such difference was detected between uranyl nitrate and
      cisplatin-treated group of rats. In short, cisplatin is comparable to uranyl
      nitrate in producing renal failure in the rat and can be considered a suitable
      alternative.

PMID- 7737233
TI  - Pharmacokinetics of carbamazepine. Part I: A new bioequivalency parameter based
      on a relative bioavailability trial.
AB  - The relative bioavailability of three carbamazepine generics available in Turkey,
      were investigated in 5 healthy male volunteers. When issuing a license to any
      drug, FDA stipulates at most a difference of 20% from the reference drug only in
      peak concentration and AUC (area under the curve). This condition may cause some
      problems, as two generics of the same drug can yield the same total amount (AUC)
      and can be accepted as bioequivalent despite different curves of the two drugs.
      In this study, to compare drugs from the point of view of bioequivalency, we
      suggest a new calculation method that takes into account ka (absorption rate
      constant), ke (elimination rate constant), tmax (time to peak), MRT (mean
      residence time) and AUC. Should this formula be used in comparison of
      bioequivalency, all the parameters related to the kinetics of drugs will have
      been taken into account. The suggested parameter is: [formula: see text] However,
      amongst three carbamazepine generics-Tegretol, Temporol and Karazepin-the most
      desirable curve is that of Tegretol, while bioavailability values are
      respectively F = 0.86, 0.93, 0.85 and AUC = 145, 161, 127. The A parameter values
      are respectively 49.3, 47.2, 42.9.

PMID- 7737238
TI  - Dose dependent tiracizine disposition in healthy volunteers: serum and urine
      kinetics and dose related ECG-changes.
AB  - The pharmacokinetics of tiracizine, a new class I antiarrhythmic agent, and 3 of
      its metabolites were assessed in serum and urine of 8 healthy extensive
      metabolisers after single oral administration of 50, 100, and 200 mg tiracizine
      hydrochloride. Additionally, tiracizine induced ECG-changes were compared between
      the different doses. With increasing doses enhancement of AUC and Cmax of
      tiracizine and its metabolites revealed a slight deviation from linearity
      indicated by exceeding the upper limits of the 95% nonparametric confidence
      interval set by 0.8-1.2 for the ratio (dose corrected parameters after the 100
      and 200 mg dose, respectively)/(parameters after 50 mg). The increase of the dose
      corrected parameters after the 200 mg dose was about 1.3-fold compared with the
      50 mg parameters for the parent compound as well as its metabolites. The
      significant decrease of the renal clearance of all 4 substances with increasing
      doses indicates that saturable tubular secretion mainly accounts for non
      linearity. Due to the occurrence of non-linear (tubular secretion) as well as
      linear (glomerular filtration, hepatic metabolism) elimination in parallel,
      however, it is concluded that saturable tubular secretion is of minor importance
      at higher doses and should not be overestimated. However, there was some evidence
      for saturable hepatic tiracizine metabolism in 4 of the 8 participants.
      Therefore, a fall of apparent intrinsic clearance has also to be taken into
      consideration, especially at higher doses. PQ- and QRS-intervals were prolonged
      in a dose dependent manner and culminated at 1 h after drug intake. QTc-time,
      however, remained unchanged. A log-linear relationship between serum
      concentrations of the parent compound and PQ- as well as QRS-time is suspected
      for serum levels about 80 ng/ml, but has to be confirmed by individual
      pharmacokinetic-pharmacodynamic modelling. PQ- and QRS-intervals might be
      suitable for tiracizine therapeutic monitoring.

PMID- 7737239
TI  - Pharmacokinetics and metabolism of diltiazem in rats following a single intra
      arterial or single oral dose.
AB  - Diltiazem (DTZ) 20 mg/kg was given to male Sprague-Dawley rats either orally
      (p.o.) or intra-arterially (i.a.) over a 5 min period (n = 6 for each group).
      Plasma concentrations of DTZ and its major basic metabolites were determined by
      high performance liquid chromatography assay (HPLC) as previously described over
      a 10 h period. The major metabolites found in the rat plasma were M2, followed by
      M6, MA, M1, and then M4. The metabolite Mx was measurable only in some of the
      plasma samples, and MB was not detected in this species. The mean apparent half
      life (t1/2) of the measurable metabolites were longer than the parent DTZ. The
      metabolism profiles were qualitatively similar between the two routes of
      administration. Quantitatively, however, the plasma concentrations of the
      metabolites were higher after the i.a. route. These results are in agreement with
      a previous study reported in rabbits, and suggest that deacetylation of DTZ and
      MA in the blood is extremely important in this species.

PMID- 7737237
TI  - Mouse liver microsomes (MLM) protect erythrocytes against trifluoperazine (TFP)
      induced and mechanical hemolysis which are due to TFP microsomal transformation
      and to the action of an unidentified water-soluble microsomal factor (UF).
AB  - Trifluoperazine (TFP), a phenothiazine derivative, produces either hemolysis or
      protection of erythrocytes under isosmotic conditions in a dose-dependent manner.
      The hemolytic effect of TFP is abolished in the presence of mouse liver
      microsomes (MLM) which is due, in part, to drug incorporation, transformation and
      a MLM enzyme driven metabolism. An unidentified water-soluble factor (or factors)
      derived from MLM has been found to protect erythrocytes against both mechanical
      and TFP-induced isosmotic hemolysis.

PMID- 7737236
TI  - Characterization of N-benzylcarbazole and its metabolites from microsomal
      mixtures by tandem mass spectrometry.
AB  - The metabolism of N-benzylcarbazole (NBC) was studied in vitro using hamster
      hepatic microsomes to establish whether the corresponding amide is formed. This
      work was carried out in order to see if the extremely low pka characteristic of
      such a benzylic amine would allow the formation of the carbonyl derivative. No
      amide formation was observed. However, a number of metabolic products were
      detected using HPLC, including the oxidative debenzylation products, namely
      carbazole and benzaldehyde, together with 2 phenolic isomers of NBC. These
      products were tentatively characterized by their UV spectra using a rapiscan UV
      detector connected to HPLC equipment. The structural characterization of these 4
      metabolites, together with unchanged substrate, was carried out using desorption
      electron impact tandem mass spectrometry (DEI-MS/MS) on a hybrid instrument with
      EBQ1Q2 configuration.

PMID- 7737241
TI  - The pattern of motor deficits in relation to the site of stroke lesions.
AB  - Thirty-two patients with hemispheric stroke lesions of distinct cortical
      functional zones (premotor, precentral, parietal) or of striatocapsular or
      striatothalamic subcortical territories were scored at the acute and chronic
      stage for the following sensorimotor arm-hand functions: force, praxis, motor
      attention, sensation and dexterity. The selection criterion was that in spite of
      the wide variation of lesion sites all patients had hemiparesis as the presenting
      clinical sign. Analysis of the scores showed that most patients showed apraxia,
      motor neglect or disturbed sensation in addition to hemiparesis. The distribution
      and severity of these deficits varied, so that different lesion groups showed
      different patterns. The actual functional impairment of arm-hand function was
      determined by the combined effect of these different sensorimotor dysfunctions.

PMID- 7737240
TI  - Stable isotope methodology for studying the performance of metoprolol Oros
      tablets in comparison to conventional and slow release formulations.
AB  - Metoprolol Oros tablets were designed to deliver their drug content as a constant
      rate over a period of time longer than that currently recorded with slow-release
      dosage forms. The bioavailability of 7/95, 14/190 and 21/285 Oros tablets was
      compared to that of either 100 mg conventional or 200 mg slow-release Lopresor
      tablets in 3 two-period change over experiments. In each experiment, 6 healthy
      volunteers received intravenous deuterated metoprolol concomitantly with one of
      the Oros systems or with one of the other two formulations. The Oros tablets gave
      rise to lower and steady plasma levels of metoprolol over 24 h than the other
      formulations. Their mean absorption time was around 3 times longer than that of
      the slow-release tablets. The amount of the drug absorbed unchanged was linearly
      related to the dose. The influence of the gastrointestinal transit time on the
      performance of Oros tablet was limited. These studies demonstrated the value of
      the stable isotope methodology in bioavailability assessment for drugs presenting
      a high inter-subject variability in their plasma clearance such as metoprolol.

PMID- 7737242
TI  - Hyperkinetic motor behaviors contralateral to hemiplegia in acute stroke.
AB  - Motor behaviors on the 'good side' of the body, i.e. ipsilateral to the
      hemispheric lesion, have not been studied systematically. We assessed motor
      behaviors in 20 consecutive patients during the acute phase (first 1-2 weeks) of
      a hemispheric stroke with hemiparesis. The behaviors were essentially rotations
      of the head, neck, eyes and trunk, orofaciopharyngeal or limb stereotypes,
      compulsive manipulation of the surroundings, or passive mobilization of the
      paralyzed arm or leg. These behaviors were found only with large infarcts in the
      territory of the internal carotid artery, middle cerebral artery and/or the
      anterior cerebral artery (ACA). All but two ACA infarcts involved the internal
      capsule and basal ganglia. The severity of the motor deficit and the presence of
      aphasia, neglect, or sensory loss were significantly correlated with the motor
      behaviors. Although the understanding of these behaviors remains unclear, we
      suggest that they may represent the clinical expression of early plastic changes
      of brain maps and circuits after an acute lesion; this is probably an active
      process induced by disinhibition, in order to establish new compensatory
      pathways.

PMID- 7737243
TI  - Potentially effective therapies for acute ischemic stroke.
AB  - Acute ischemic stroke remains without an effective therapy to improve outcome. As
      knowledge about the basic pathophysiology has expanded, rational approaches to
      therapy have evolved. The frequent presence of arterial occlusion suggested that
      thrombolytic therapy might be a viable approach. Both clot-specific and
      nonspecific thrombolytic agents are currently being evaluated in clinical trials.
      Focal brain ischemia induces a variety of cellular consequences. Neuroprotective
      therapies designed to ameliorate these metabolic abnormalities are also being
      evaluated in clinical trials. A key feature of all these clinical trials is the
      rapid initiation of therapy. In the future, we can anticipate combined therapy
      trials with both neuroprotective and thrombolytic drugs, an approach which is
      likely to be more beneficial than either one in isolation.

PMID- 7737244
TI  - Evaluation of fifth nerve dysfunction in 136 patients with middle and posterior
      cranial fossae tumors.
AB  - One-hundred thirty-six patients operated on for extra-axial tumors of the
      posterior and middle cranial fossae were retrospectively evaluated to define the
      relevance of trigeminal nerve dysfunction and to correlate clinical and surgical
      observations. The following data are reported: tumor types, presence of specific
      trigeminal symptoms and signs, mean duration of symptomatology, anatomical
      relation between tumor and fifth nerve. Trigeminal symptoms were present in 45
      subjects (33.08%) with a mean duration of 23.56 months. Frequency of symptoms was
      different in various oncotypes. Fifth nerve disturbances were the symptom of
      onset in 18 subjects (13.23%). A tumoral involvement of the nerve was reported at
      surgery in 73 patients (53.67%) and was defined as contact, compression or
      infiltration. Postoperatively, 12 patients showed an improvement of fifth nerve
      disturbances. A statistically significant difference (p < 0.05) was found in: (1)
      the incidence of symptoms in patients with and in those without anatomical
      trigeminal involvement: (2) the incidence of signs in the same groups; (3) the
      incidence of postoperative relief in patients with fifth nerve compression
      compared to patients with different surgical findings; (4) the incidence of
      postoperative relief in patients with typical trigeminal neuralgia compared to
      those with other symptoms.

PMID- 7737245
TI  - History of brain and epidural metastases from breast cancer in relation with the
      disease evolution outside the central nervous system.
AB  - We reviewed 89 breast cancer patients with brain or epidural metastases in order
      to see whether a parallelism could be found between disease evolution inside and
      outside the central nervous system. One-fifth of the patients with brain
      metastases did not have any other site of relapse before neurological
      complication. Among the 38 patients who developed brain metastases and had a
      prior history of relapse outside the brain, 12 had control of constant
      extracranial sites while disease was progressing at these sites in 26 of them. In
      the epidural metastases group, all patients but 4 had progressive disease
      elsewhere when neurological complication appeared.

PMID- 7737246
TI  - Treatment of hemifacial spasm with botulinum toxin. Value of preinjection
      electromyography abnormalities for predicting postinjection lower facial paresis.
AB  - Thirty-two patients with hemifacial spasm were treated with 61 botulinum toxin
      (BT) injections. Some patients had post-BT lower facial paresis (LFP+group) while
      others did not suffer this side effect (LFP-group). Abnormal electromyography
      (EMG) recordings were more frequent in the LFP+ group (6/11) than in the LFP-
      group (3/21; p < 0.05). This result suggests that an EMG performed before any BT
      injection could detect the patients with a higher risk for this side effect. The
      first dose of BT might be lowered in such cases.

PMID- 7737247
TI  - Parkinsonism in patients with lucanar infarcts of the basal ganglia.
AB  - Forty-five patients with CT findings of lucanar infarcts in the basal ganglia
      (LIBG) were included in this study. The patients were divided into those with
      lacunes in the caudate nucleus, lentiform nucleus or both caudate and lentiform
      nuclei. Linear measurements of ventricular spaces were also performed. Clinical
      evaluation disclosed parkinsonism in 17 patients (38%), strokes with
      contralateral hemiparesis in 14 (31%), while 9 (20%) had both parkinsonism and
      hemiparesis. The location and number of infarcts did not correlate with the
      clinical presentation. We conclude that LIBG are commonly associated with
      parkinsonism and that CT studies may help in the delineation of vascular
      parkinsonism.

PMID- 7737248
TI  - Corticobasal degeneration: neuropsychological assessment and dopamine D2 receptor
      SPECT analysis.
AB  - We report a case of clinically diagnosed corticobasal degeneration, in whom
      neuropsychological testing was performed along with functional imaging with IBZM
      SPECT. HM-PAO SPECT showed marked perfusion asymmetry in parietal cortical
      regions, lower to the right, contralateral to the most affected side. IBZM SPECT,
      which gives information about postsynaptic dopaminergic D2 receptors, showed
      severe reduction of tracer uptake in the right basal ganglia. Our findings
      suggest that a postsynaptic lesion in the basal ganglia might account for the
      lack of response of extrapyramidal motor symptoms to dopaminergic agonists in
      corticobasal degeneration.

PMID- 7737249
TI  - Nephrolithiasis and nephrocalcinosis in cerebrotendinous xanthomatosis: report of
      three siblings.
AB  - We report the existence of nephrocalcinosis (NC) and/or nephrolithiasis (NL) in
      three siblings with cerebrotendinous xanthomatosis (CTX). Incomplete renal
      tubular acidosis (RTA) type 1 is also found in these three siblings after the
      evaluation of renal acidification function. Although the association of RTA with
      NC and/or NL is well known, they are rarely reported in CTX patients.

PMID- 7737250
TI  - Utilization behavior after right thalamic infarction.
AB  - We report a patient who showed exaggerated responses to external cues
      (utilization behavior), motor impersistence, and a right-hand-predominant
      instinctive grasp reaction after right thalamic infarction. High-resolution
      computed tomography with stereotaxic lesion localization revealed almost complete
      destruction of the ventroanterior nucleus and intralaminar nuclei of the right
      thalamus; the dorsomedial nucleus was only partially involved. Single photon
      emission computed tomography revealed hypoperfusion in the right thalamus and
      over the entire right cerebral cortex with some prominence in the frontal area.
      From these observations, we believe that the utilization behavior in our case was
      caused by the disturbance in maintaining cortical tone of the right hemisphere as
      well as by the dysfunction of the right frontal lobe, both secondary to the
      damage to the right ventroanterior nucleus and intralaminar nuclei.

PMID- 7737251
TI  - A case of cortical tremor as a variant of cortical reflex myoclonus.

PMID- 7737252
TI  - Molecular genetics of Alzheimer disease: identification of genes and gene
      mutations.
AB  - Alzheimer disease (AD), the major form of senile dementia, is rapidly becoming a
      major health problem in developed countries since as populations live longer the
      number of elderly people continues to grow. Simultaneously, the number of AD
      cases is increasing since AD is mainly a late-onset disorder and since no
      effective therapies are available. The primary causes of AD have not yet been
      elucidated. However, several researchers in different disciplines are actively
      engaged in AD research with one ultimate goal, i.e. trying to understand the
      disease pathology. Knowledge of the biochemical basis of the disease may
      eventually lead to a therapy which either prevents AD or allows AD patients to be
      treated. One such discipline is molecular genetics. The aim of molecular genetic
      studies is to identify genes that are either responsible for or contribute to the
      expression of AD. Once such a gene is identified, studies of its normal and/or
      abnormal gene product may help us understand the primary disease mechanisms and
      lead to more effective therapy. Currently, 3 genetic loci have been identified
      that predispose to AD: AD1 on chromosome 21, AD2 on chromosome 19, and AD3 on
      chromosome 14. This review aims at summarizing the progresses that have made in
      identifying genes and gene mutations that predispose to AD.

PMID- 7737254
TI  - Prostate cancer: hormonal treatment and treatment of advanced disease.
      Proceedings from the 4th International Symposium on Recent Advances in Urological
      Cancer Diagnosis and Treatment. Paris, June 22-24, 1994.

PMID- 7737253
TI  - A phase III randomized trial comparing the efficacy and safety of the 3-monthly
      10.8-mg depot of Zoladex with the monthly 3.6-mg depot in patients with advanced
      prostate cancer. Dutch South East Cooperative Urological Group.

PMID- 7737256
TI  - A phase III trial (RTOG 8610) comparing external-beam irradiation plus short-term
      maximal androgen blockade with radiation therapy alone for locally advanced
      prostate cancer. The Radiation Therapy Oncology Group.

PMID- 7737255
TI  - French multicentre trial comparing Casodex (ICI 176,334) monotherapy with
      castration plus nilutamide in metastatic prostate cancer: a preliminary report.
AB  - This trial compares Casodex (ICI 176,334) monotherapy with the combination of
      castration (medical or surgical) plus nilutamide. The trial is now closed to
      entry, 270 patients having been recruited from 32 French centres. As it is too
      early to present efficacy data, only patient characteristics and interim
      tolerability data appear in this paper. In the combined treatment group,
      interstitial pneumonitis (4.5%) was observed, leading to withdrawal from the
      trial. Other adverse events leading to withdrawal included dyspnoea and ocular
      problems. There was also 1 case of hepatitis in this treatment group. In the
      Casodex treatment group, only 6 patients (as compared with 13 in the combined
      treatment group) withdrew from the trial because of adverse events. As expected
      with this group, the adverse events were mainly pharmacological effects of an
      anti-androgen as monotherapy. In the majority of patients, the effects of
      gynaecomastia and breast tenderness did not result in withdrawal.

PMID- 7737257
TI  - A multicentre trial of combined neoadjuvant androgen blockade with Zoladex and
      flutamide prior to radical prostatectomy in prostate cancer. The European Study
      Group on Neoadjuvant Treatment.

PMID- 7737258
TI  - Update of monotherapy trials with the new anti-androgen, Casodex (ICI 176,334).
      International Casodex Investigators.
AB  - Casodex (ICI 176,334) is a non-steroidal anti-androgen, which has a half-life
      compatible with once-daily oral dosing. In an open, phase II study on 267
      patients given Casodex, 50 mg/day, an overall objective response (i.e. partial
      regression) was seen in 55.5% of patients (146 of 263) with a further 15.6% (41
      of 263) having stable disease. Two of three randomized, phase III studies
      conducted with Casodex, 50 mg/day, showed it to be inferior to castration (either
      medical or surgical) on time to treatment failure and time to progression. A
      subsequent overview analysis of survival from these three studies showed a
      statistically significant difference in favour of castration. Prostate specific
      antigen (PSA) at 3 months correlated well with clinical outcome in the phase III
      studies of Casodex, 50 mg/day; a greater fall in PSA at 3 months was observed
      with Casodex, 100 and 150 mg/day, in an open dose-ranging study. As no
      significant tolerability issues were reported, further investigation of Casodex
      at these higher doses is in progress. All studies in which Casodex has been
      investigated have shown it to be a well-tolerated anti-androgen with a good side
      effect profile compared with those reported for other available non-steroidal
      anti-androgens.

PMID- 7737259
TI  - Effect of genetic risk load defined by HLA-DQB1 polymorphism on clinical
      characteristics of IDDM in children.
AB  - Clinical and autoimmune characteristics of 150 diabetic children of mean age 7.8
      years (SD 4.1 years) were recorded at clinical manifestation and during the first
      2 years of IDDM in order to investigate whether subjects with high risk HLA-DQB1
      genotypes differ from those without these risk markers. When comparing subjects
      with the DQB1*0302/0201, DQB1*0302/x, DQB1*0201/x, or other DQB1 genotypes (x =
      no protective allele), no differences were found in the age of the subjects at
      diagnosis, the duration of hyperglycaemic symptoms, or the length of clinical
      remission. The frequency of islet cell antibodies (ICA) and quantitative serum
      levels of these antibodies were of the same magnitude in all four groups. During
      the initial 2 years of IDDM serum C-peptide concentrations were observed to be
      inversely related to the degree of genetic risk (P < 0.001 in two-way analysis of
      variance for repeated measures), the lowest C-peptide levels being observed in
      the group of DQB1*0302/0201 heterozygotes (P < 0.001 vs. DQB1*0201/x; P < 0.01
      vs. DQB1*0302/x; P = 0.05 vs. others). On the other hand, the subjects with the
      DQB1*0201 genotype had the highest serum C-peptide concentrations, the levels
      being even higher than those of the patients carrying neutral or protective DQB1
      genotypes (P < 0.01). These subjects also had lower daily insulin doses and blood
      glycated haemoglobin A1 (HbA1) levels over the initial 2 years of the disease
      when compared with the DQB1*0302/0201 heterozygotes (P < 0.05 and P < 0.01,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737260
TI  - Gastrointestinal motor and secretory responses to cholinergic stimulation in
      humans. Differential modulation by muscarinic and cholecystokinin receptor
      blockade.
AB  - The present study investigated how a cholinergic agonist modifies interdigestive
      motility and secretion of the upper gastrointestinal tract and how muscarinic and
      cholecystokinin receptor blockade interfere with this direct cholinergic
      stimulation. In eight healthy volunteers, gastrointestinal motor and secretory
      responses to bethanechol (12.5, 25, and 50 micrograms kg-1 h-1) with and without
      a background of atropine (5 micrograms kg-1 h-1) or loxiglumide (10 mg kg-1 h-1)
      were studied. Stepdoses of bethanechol caused a parallel stimulation of
      antroduodenal motility and gastropancreatic secretion (P < 0.01) without inducing
      a fed pattern. However, duration of phase I was shortened (P < 0.05). Only high
      doses of bethanechol enhanced gastrin (P < 0.05), cholecystokinin (P < 0.05), and
      pancreatic polypeptide (P < 0.01) release. Atropine completely antagonized motor
      and secretory responses to cholinergic stimulation. Loxiglumide left
      cholinergically stimulated motility and pancreatic enzyme secretion unaltered.
      With co-infusion of bethanechol and loxiglumide, PP release dropped by 63% (P <
      0.01); gastric acid output, gastrin and CCK release increased by 56%, 16%, and
      25%, respectively (P < 0.05). We conclude that stimulation by a cholinergic
      agonist preserves the interdigestive pattern. Low dose muscarinic receptor
      blockade abolishes cholinergic stimulation over the full dose range. Inhibition
      of somatostatin release would explain stimulation of gastrin release and gastric
      acid secretion with co-infusion of bethanechol and loxiglumide. Endogenous CCK
      appears to interact with direct cholinergic stimulation at the pancreatic PP cell
      and the gastric D-cell but not at pancreatic acinar and antroduodenal smooth
      muscle cells.

PMID- 7737261
TI  - Relationship between fractional calcium absorption and gastric emptying.
AB  - The relationship between calcium absorption and gastric emptying and the
      precision of measurement of fractional calcium absorption using a single isotope
      technique were evaluated in 14 normal postmenopausal women (age range 61-72
      years). On two occasions separated by between 5 and 15 days, each subject was
      given 250 mL water containing 0.2 MBq of 45Ca in 20 mg of calcium carrier as the
      chloride, 20 mg kg-1 paracetamol and 9 MBq of 99mTc sulphur colloid. Venous blood
      samples were taken at -2, 15, 30, 45, 60, 90, 120, 150 and 180 min after
      consumption of the drink, and gastric emptying (GE) was monitored with a gamma
      camera. Fractional calcium absorption in the first hour (alpha 6) was calculated
      from the blood samples obtained at 15, 30, 45, 60, 90 and 120 min. An absorption
      rate was also derived from the 60 min sample using only a calibration curve
      (alpha 1). There were close correlations between radiocalcium absorption on the
      two study days (r = 0.89, P < 0.001 for both alpha 1 and alpha 6) and between
      alpha 1 and alpha 6 (r = 0.93, P < 0.001). Plasma paracetamol concentrations at
      15 min were directly related to the early phase of GE (r = 0.42, P < 0.05). In
      contrast, calcium absorption was inversely related to GE (r = 0.45, P < 0.05). We
      conclude that radiocalcium absorption is not greatly influenced by gastric
      emptying rate and that the single blood sample procedure has similar precision to
      the six-blood sample test.

PMID- 7737262
TI  - G-protein mutations in human pituitary adrenocorticotrophic hormone-secreting
      adenomas.
AB  - Activating mutations of Gs alpha (gsp) and Gi2 alpha (gip) have been described in
      various endocrine neoplastic conditions. The objective of this study was to
      assess the prevalence of gsp and gip mutations in human adrenocorticotrophin
      hormone-secreting pituitary adenomas. Adrenocorticotrophin hormone production and
      secretion by pituitary corticotroph cells is under stimulatory control by
      corticotrophin-releasing factor, acting via the production of cyclic AMP.
      Interference with this regulatory pathway as a result of G-protein dysfunction
      could lead to disordered corticotroph cell function and growth. We have studied
      32 corticotroph adenomas for the presence of gsp and gip mutations using site
      directed oligonucleotide hybridization of polymerase chain reaction-amplified
      DNA. G-protein gene mutations were identified in three (9%) tumours: gsp
      mutations were demonstrated in two tumours at codon 227, and a gip mutation was
      identified in one tumour at codon 179. We did not observe a correlation between
      tumour phenotype and the presence of G-protein gene mutations. We conclude that G
      protein gene mutations are an uncommon abnormality in corticotroph adenomas.

PMID- 7737263
TI  - Screening for germline mutations of the p53 gene in familial breast cancer
      patients.
AB  - The constitutive DNA from members of four families showing predisposition to
      breast cancer was amplified by PCR in the region of exons 5, 6, 7 and 8 of the
      p53 proto-oncogene. Single-strand conformation polymorphism (SSCP) gels were used
      to compare patient DNA with mutant and wild-type control samples. No cases of
      anomalous mobility were observed in samples from the susceptible families. The
      lack of inherited mutations was confirmed for exons 5 and 7 by solid-phase DNA
      sequencing. The results lend further support to the view that inherited mutations
      in p53 alleles are not a significant contributor to breast cancer predisposition
      and it is not, therefore, clinically worthwhile to screen predisposed or
      potentially predisposed families for germline mutations in the p53 gene.

PMID- 7737264
TI  - Exhaled nitric oxide concentration and amniotic fluid nitrite concentration
      during pregnancy.
AB  - We have assessed fetal and maternal nitric oxide (NO) production in pregnancy.
      Exhaled NO and amniotic fluid nitrite concentrations were measured by
      chemiluminescence between 10 and 42 weeks of pregnancy. Exhaled NO concentrations
      did not alter significantly during gestation. In contrast, there was a
      significant change in mean amniotic fluid nitrite concentration in late pregnancy
      (P < 0.001). The finding of decreased amniotic nitrite concentrations after 37
      weeks of gestation support the hypothesis that reduced NO production may
      contribute to increased uterine activity in late pregnancy.

PMID- 7737265
TI  - Integrins: structure, biological functions and relevance in viral chronic
      hepatitis.

PMID- 7737266
TI  - Heterozygous familial hypercholesterolaemia is associated with pathological
      exercise-induced leakage of muscle proteins, which is not aggravated by
      simvastatin therapy.
AB  - The objective of this study was to assess the relationship between therapy with
      the HMG-CoA reductase inhibitor simvastatin and muscle damage and the possible
      causal role of hypercholesterolaemia. The exercise-induced release of muscle
      proteins as a parameter of muscle damage was studied in two equicholesterolaemic
      groups of male patients with heterozygous familial hypercholesterolaemia (FH);
      one group without treatment, the second group on simvastatin. To assess the role
      of cholesterol, a third group of healthy male volunteers was studied as well. The
      study took place at the Lipid Clinic of an 800-bed University Hospital. One group
      of 21 male patients with heterozygous FH did not receive treatment, except for a
      lipid-lowering diet. A second group of 13 male FH patients were treated with 40
      mg simvastatin day-1 for at least 1 year and matched for cholesterol levels with
      the first group. A third group consisted of 25 normocholesterolaemic male
      controls. All subjects underwent a 45 min lean body mass (LBM) standardized
      ergometer muscle provocation test (2 Watt/kg LBM). Levels of creatine kinase (CK)
      and myoglobin (Mb) were assessed before and 1 and 8 h after exercise and compared
      with baseline levels. The exercise-induced release of muscle proteins is
      reflected by peak CK and Mb levels expressed as a percentage of baseline levels.
      The exercise-induced increase in Mb and CK levels did not differ between
      untreated and simvastatin-treated FH patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737267
TI  - Bone mineral density and its relationship to skin colour in Caucasian females.
AB  - Low bone mineral density (BMD) is associated with a high risk of osteoporosis and
      fracture. While women with darker skin, such as women of American African origin,
      are reputed to have lower risk osteoporosis and fractures compared with women
      with fair skin such as Caucasian women, with Oriental women having intermediate
      levels of risk, the reasons for these differences are not clear. We examined the
      relationship between BMD and skin colour in a population based study of 2005
      Caucasian women with a mean age of 58.1 years, resident in Cambridge and
      categorized into fair, medium and dark complexions by self-report. There was no
      difference between the three categories of skin colour with regard to body size
      or life-style characteristics. Women with self-reported fair skin had lowest BMD
      values, women with self-reported dark skin had highest BMD values, and women with
      self-reported medium skin colour had intermediate values at all sites. These
      differences were significant at the trochanter and Ward's triangle of the hip (P
      values of 0.01 and 0.03, respectively). These associations were independent of
      age and weight. The associations remained after stratifying for smoking habit and
      years since menopause. In a cohort of Caucasian women resident at latitude 52
      degrees North, fair-skinned women have lower BMD values than darker-skinned
      women. This association between skin colour and BMD may reflect sunlight exposure
      times and underlying vitamin D status.

PMID- 7737268
TI  - Effects of epidermal growth factor (EGF), platelet-derived growth factor (PDGF)
      and fibroblast growth factor (FGF) on human adipocyte development and function.
AB  - We investigated the effects of epidermal growth factor (EGF), platelet-derived
      growth factor (PDGF) and fibroblast growth factor (FGF) on the differentiation of
      human adipocyte precursor cells and some metabolic aspects of newly formed fat
      cells kept in primary culture. Exposure of stromal cells from human adipose
      tissue to EGF (0.01-100 ng mL-1) resulted in a dose- and time-dependent decrease
      in the number of developing fat cells and the activity of glycerol-3-phosphate
      dehydrogenase (GPDH), a marker of adipose differentiation. Continuous presence of
      EGF completely blocked lipid accumulation with a ED50 in the range of 0.2 ng mL
      1. This inhibitory action of EGF was associated with a potent stimulation of cell
      proliferation, up to 8-fold compared with cultures in the absence of EGF. PDGF
      (0.1-50 ng mL-1) and FGF (0.1-100 ng mL-1) provoked a less marked suppression of
      GPDH activities which was significant at concentrations of 10 ng mL-1 and higher.
      A 12 day exposure to EGF of differentiated cells was followed by a suppression of
      GPDH and, again, a significant increase in cell number. Concomitantly, a distinct
      loss of cellular lipids was observed in the newly formed adipocytes. This effect
      could be partly explained by a stimulation of lipolysis, since EGF caused an
      increase of glycerol in the culture medium. Addition of PDGF or FGF to newly
      developed fat cells had no effect on lipolysis but, at higher concentrations,
      also decreased GPDH activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737269
TI  - Characterization of putrescine transport across the intestinal epithelium: study
      using isolated brush border and basolateral membrane vesicles of the enterocyte.
AB  - Putrescine transport was investigated in isolated brush border and basolateral
      membrane vesicles prepared from the rabbit enterocyte. Brush border vesicles were
      oriented right-side-out and basolateral vesicles inside-out, forming a model
      representing uptake and extrusion across the intestinal epithelium. Putrescine
      transport across both membranes was initially rapid, and 66% of the equilibrium
      uptake was achieved within the first minute. According to osmoplots and
      measurements at 4 degrees C, 20% of total incorporation presented binding to the
      membrane. In order to estimate actual uptake into the vesicles, Km was calculated
      from the differences in putrescine incorporation at 37 degrees C and 4 degrees C,
      and was 12.7 mumol L-1 for brush border uptake and 38.2 mumol L-1 for basolateral
      extrusion. Putrescine uptake into brush border and basolateral membrane vesicles
      was not enhanced in the presence of an Na+ gradient. When Na+ was substituted
      with an uncharged solute, mannitol, putrescine incorporation was increased,
      indicating that putrescine uptake is not Na(+)-dependent and that cations might
      interfere with the carrier. Paraquat and methylglyoxalbis(guanylhydrazone), known
      to share the polyamine transport system, inhibited putrescine incorporation in
      both membrane vesicle preparations. Basolateral carrier showed significantly
      higher sensitivity to cations. We conclude that putrescine uptake across the
      apical membrane and extrusion across the basolateral membrane of the enterocyte
      are mediated by two different and independent carriers which differ in their
      electrical properties.

PMID- 7737270
TI  - Surface expression of beta 2-microglobulin-associated thymus-leukemia antigen is
      independent of TAP2.
AB  - Mouse thymus-leukemia antigen (TL), like other major histocompatibility complex
      (MHC) class I-b antigens, displays signs of a specialized function. It is
      normally expressed at high levels on immature thymocytes and at moderate levels
      on gut epithelium and activated mature T cells. A promoter/enhancer region unique
      among class I genes accounts for this narrow range of tissue distribution. Like
      most other class I molecules, TL is dependent upon endogenous beta 2
      microglobulin (beta 2m) for transport to the surface. However, here we show that
      unlike most other MHC class I molecules, TL is expressed efficiently in the
      absence of functional transporter associated with antigen processing subunit 2
      (TAP2). A putative fourth TLa gene cloned from A.SL1 cells was expressed in RMA
      and RMA-S cells. In bulk transformants, TL expression is higher in TAP2-RMA-S
      cells than in wild-type RMA cells, and is not elevated by incubation at reduced
      temperatures or exposure to exogenous beta 2m. Analysis of immunoprecipitated
      molecules by polyacrylamide gel electrophoresis in the presence of sodium dodecyl
      sulfate indicates that TL is processed normally in RMA-S cells and is associated
      with beta 2m both intracellularly and at the cell surface. However, TL heavy
      chains expressed on the cell surface in the absence of TAP2 are cleaved to a
      predominant 38 kDa fragment, presumably the result of an altered conformation
      that renders TL more susceptible to proteolysis. These results suggest that while
      TL may normally acquire TAP2-dependent peptides, this class I-b molecule does not
      require them for efficient export to, and stable expression at the cell surface.

PMID- 7737271
TI  - Heterogenous glycosylation of ICAM-3 and lack of interaction with Mac-1 and
      p150,95.
AB  - Intercellular adhesion molecule (ICAM)-1, ICAM-2, and ICAM-3 have been identified
      as counter-receptors for the leukocyte integrin lymphocyte function-associated
      antigen 1 (LFA-1). The other leukocyte integrins, Mac-1 and p150,95, also
      interact with ICAM-1. ICAM-1 and ICAM-3 are highly homologous, and an undefined
      ligand for Mac-1 is present on neutrophils where ICAM-3 is well expressed. In
      addition, glycosylation has been shown to affect the interaction of ICAM-1 with
      Mac-1. We therefore sought to characterize ICAM-3 heterogeneity and determine
      whether ICAM-3 was a ligand for either Mac-1 or p150,95. Despite extensive
      differences in N-linked glycosylation, ICAM-3 purified from lymphoid cells and
      from neutrophils supports adhesion of LFA-1-bearing cells equally well; however,
      neither supports adhesion of Mac-1 or p150,95-expressing chinese hamster ovary
      cell transfectants. Similarly, purified Mac-1 does not support adhesion of ICAM-2
      or ICAM-3-expressing L cell transfectants. ICAM-3 on neutrophils does not
      participate in Mac-1-dependent homotypic aggregation. Thus, ICAM-3 is not a
      counter-receptor for either Mac-1 or p150,95.

PMID- 7737272
TI  - Co-ligation of mouse complement receptors 1 and 2 with surface IgM rescues
      splenic B cells and WEHI-231 cells from anti-surface IgM-induced apoptosis.
AB  - Recent studies have shown that complement receptors play important roles in both
      T-dependent and T-independent B lymphocyte responses to low doses of antigen (Ag)
      in vivo. Complement activation by either the classical or alternative pathway
      results in the covalent binding of C3 molecules to Ag in forms that ligate
      complement receptors type 1 (CR1) and 2 (CR2). We hypothesized that C3-bound Ag
      might cross-link CR2 and/or CR1 with surface (s)IgM and alter the signal that
      would be transduced through sIgM by Ag binding alone. One result of the altered
      signal could be the rescue of B lymphocytes from apoptosis that would otherwise
      be induced by the binding of certain types of Ag alone. We find that co-cross
      linking of mouse CR2 and CR1 with sIgM rescues both resting B cells and WEHI
      231.7 cells from apoptosis induced by sIgM ligation in a fashion similar to that
      found using soluble mouse CD40 ligand (mCD40L). Anti-CR2/CR1-mediated rescue
      requires co-cross-linking of the receptors with sIgM, and has an additive effect
      on mCD40L-mediated apoptosis rescue. Based on these results, it is likely that
      the CR2/CR1-derived signal is cooperative with T cell-derived signals such as
      CD40L and interleukin-4.

PMID- 7737273
TI  - Cytokine-dependent regulation of growth and maturation in murine epidermal
      dendritic cell lines.
AB  - We have recently established dendritic cell (DC) lines (XS series) from the
      epidermis of newborn mice by repeated feeding with granulocyte/macrophage-colony
      stimulating factor (GM-CSF) and culture supernatants from skin-derived stromal
      cell lines (NS series). XS lines resemble resident Langerhans cell (LC), which
      are immature DC that reside in epidermis, by their surface phenotype and antigen
      presenting profile. XS lines further resemble resident LC in that they express
      mRNA for interleukin-1 beta and macrophage inflammatory protein (MIP)-1 alpha,
      and by the absence of mRNA for IL-6. Their growth is promoted by GM-CSF, colony
      stimulating factor-1 (CSF-1), or NS culture supernatant, and inhibited by
      interferon-gamma or tumor necrosis factor-alpha. The expression by the XS lines
      of Ia molecules is up-regulated by GM-CSF, and down-regulated by NS supernatant.
      These results suggest the existence of negative regulatory mechanisms in which
      the growth and/or maturation of DC is suppressed by selected cytokines.

PMID- 7737274
TI  - Antibody response against poly (Glu60Ala30Tyr10) terpolymer and bacterial levan
      in kappa-deficient mice.
AB  - In murine species, the kappa (+)-bearing immunoglobulins dominate the antibody
      (Ab) repertoire with a kappa/lambda ratio of 95:5. The aim of the present study
      is to investigate the characteristics of the antibody response in kappa-deficient
      (K-/-) mice immunized with a T-dependent synthetic antigen, poly(Glu60Ala30Tyr10)
      (GAT) and a T-independent antigen, bacterial levan (BL). K-/- mice were obtained
      by targeted deletion of the J kappa C kappa gene segments. In response to GAT, K
      /- mice respond by producing increasing amounts of anti-GAT Ig lambda 1 and Ig
      lambda 2 in the primary as well as secondary response, although anti-GAT specific
      monoclonal antibodies (mAb) raised in K-/- mice are mostly of IgM isotype. The
      GAT public idiotype, GATIdX, present on all GAT-specific Ab bearing kappa light
      chain, is not detected in the sera of K-/- mice or on any of the anti-GAT lambda
      1 mAb. In response to BL, the amount of Ig lambda 1+ Ab in K-/- mice is
      comparable to the amount of Ig kappa + Ab in normal mice. However, lambda 2+ Ab
      are detected neither in wild-type nor in K-/- mice. Like kappa + Ab, the majority
      of lambda 1+ mAb are specific for beta 2-6 fructosan present in BL and rye levan
      and, to some extent, express the BL-specific idiotype, A48ld. Our results show
      that important compensatory mechanisms occur in kappa-deficient mice, restoring
      their ability to mount immune responses against a variety of T-dependent and T
      independent antigens by the alternative usage of the clonally restricted lambda
      repertoire.

PMID- 7737275
TI  - T cell antigen CD28 binds to the GRB-2/SOS complex, regulators of p21ras.
AB  - The T cell molecule CD28 provides a co-stimulatory signal that is required for T
      cell proliferation, and has been implicated in the control of T cell anergy. An
      important clue to the signaling mechanism of CD28 is the finding that CD28 can
      bind to phosphatidylinositol 3-kinase (PI 3-kinase) by means of a cytoplasmic
      phospho-YMNM (pYMNM) motif. A remaining issue concerns whether CD28 can recruit
      other intracellular signaling molecules. In this study, we show that CD28 uses
      the same pYMNM motif to recruit a second intracellular protein, GRB-2. CD28
      associated GRB-2, as detected by anti-GRB-2 immunoblotting, was found in human
      peripheral T cells, HPB-ALL and Jurkat cells. As in the case of PI3-kinase,
      antibody-induced cross-linking of CD28 induces a time-dependent recruitment of
      GRB-2. Likewise, mutation of the pY-191 residue within the pYMNM motif reduces
      GRB-2 binding. Peptide binding studies show that the SH2 domain of GRB-2 binds to
      the pYMNM motif with an affinity comparable to GRB-2/SHC, but some 10- to 100
      fold lower than the CD28/PI 3-kinase. Despite this, CD28/GRB-2 and CD28/PI 3
      kinase complexes are found to co-exist in peripheral T cells. Finally,
      immunoblotting shows that CD28 also associates with the gene product of the human
      homolog of the Drosophila Son of sevenless gene (SOS), a GRB-2-complexed guanine
      nucleotide exchange factor responsible for converting p21ras to a GTP-bound
      active state. CD28-associated GRB2/SOS is likely to serve an important link in
      the regulation of p21ras and lymphokine expression mediated by CD28.

PMID- 7737276
TI  - Serial killing by cytotoxic T lymphocytes: T cell receptor triggers
      degranulation, re-filling of the lytic granules and secretion of lytic proteins
      via a non-granule pathway.
AB  - CD8+ cytotoxic T lymphocyte (CTL) clones begin to synthesize the lytic proteins
      granzyme A, granzyme B and perforin after stimulation with allogeneic target
      cells. The lytic proteins are stored in the secretory granules which are released
      after cross-linking of the T cell receptor (TcR) upon target cell recognition.
      During lytic granule biogenesis granzyme A protein synthesis can be detected
      between 2 and 10 days after allogeneic stimulation of the CTL. Although granzyme
      A is stored in the lytic granules over this period, the majority of granzyme A
      synthesized is secreted directly from the CTL. TcR triggering of degranulation
      also results in new synthesis of the lytic proteins, which can be inhibited by
      cycloheximide (CHX). Some of the newly synthesized lytic proteins can be stored
      in the cell and refill the granules. But up to one third of granzymes A and B can
      be secreted directly from the CTL via the constitutive secretory pathway as shown
      by granzyme A enzymatic activity and immunoblots of secreted granzyme B, where
      one third of the protein fails to acquire the granule targeting signal. Perforin
      is also secreted via the constitutive pathway, both from the natural killer cell
      line, YT, and from CTL clones after TcR cross-linking. Constitutive secretion of
      the lytic proteins can be blocked by both CHX and brefeldin A (BFA). While BFA
      does not affect the directional killing of recognized targets, it abrogates
      bystander killing, indicating that bystander killing arises from newly
      synthesized lytic proteins delivered via a non-granule route. These results
      demonstrate that the perforin/granzyme-mediated lytic pathway can be maintained
      while CTL kill multiple targets. We show that CTL not only re-fill their granules
      during killing, but also secrete lytic proteins via a non-granule-mediated
      pathway.

PMID- 7737277
TI  - Diacylglycerol lipase activation and 5-lipoxygenase activation and translocation
      following TCR/CD3 triggering in T cells.
AB  - Arachidonic acid (AA) release was observed following T cell receptor (TCR)/CD3
      complex cross-linking in different tumor T cell lines as well as on purified
      peripheral T cells in vivo. Direct measurement of enzymatic activity in vitro of
      TCR/CD3-stimulated Jurkat cell extracts on labeled vesicle substrates showed that
      TCR/CD3 cross-linking resulted in AA release from sn-1,2-diacylglycerol (DAG)
      vesicles, as detected by TLC analysis, suggesting that DAG lipase was activated
      following TCR/CD3 stimulation and DAG generation. On the contrary, no
      phospholipase A2 activation was observed in response to TCR/CD3 stimulation,
      since no lyso-phospholipids were generated in vitro from either
      phosphatidylcholine or phosphatidylinositol-3,4-bisphosphate, or from
      phosphatidic acid vesicles. Moreover, the 1-DAG lipase inhibitor RHC80267
      completely blocked TCR/CD3-dependent AA release in vitro and in vivo, without
      effect upon TCR/CD3-dependent inositol-1,4,5-trisphosphate (IP3) generation.
      Importantly, evidence for further metabolism of released AA was obtained, since
      synthesis and release of cysteinyl leukotrienes (CLT), but not of leukotriene B4
      or cyclooxygenase products, could be detected by radioimmunoassay in different T
      cell lines and peripheral blood T cells following TCR/CD3 cross-linking.
      Moreover, HPLC analysis revealed an accumulation of leukotriene E4 in TCR/CD3
      stimulated Jurkat cells. This was associated with translocation of 5-lipoxygenase
      from the cytosol to the cell membranes. Finally, TCR/CD3-mediated CLT production
      was blocked by MK886, a specific inhibitor of 5-LO translocation and activation.
      Our data help define a further level in the fate of second messengers generated
      after TCR/CD3 triggering and suggest that additional mediators can play a role in
      the context of T cell activation.

PMID- 7737278
TI  - Expression and tissue localization of donor-specific complement C3 synthesized in
      human renal allografts.
AB  - Recent evidence suggests that the third component of complement, C3, is
      synthesized in renal tissue, and that increased C3 synthesis occurs in allograft
      rejection and immune complex-mediated nephritis. However, it is unclear whether
      intrinsic renal cells or migratory cells in the inflammatory infiltrate, possibly
      of recipient bone marrow origin, are the source of the C3 detected. This was
      investigated by determining the C3 allotypes of mRNA and protein produced by
      transplanted human kidney. Twenty donor-recipient pairs were examined, of which
      nine pairs had C3 allotypes that were informatively mismatched at the C3 F/S
      locus. Reverse transcriptase polymerase chain reaction (RT-PCR) followed by
      amplification refractory mutation system analysis showed intracellular donor
      specific mRNA expression in six of these nine cases, at up to 61 days post
      transplantation. Nested PCR reactions and the size of PCR products excluded
      contamination by genomic DNA. Allotype-specific staining of frozen sections of
      renal cortex demonstrated donor-derived C3 protein in both glomeruli and tubules
      of all biopsies examined, in a predominantly tubular distribution. These results
      imply that at least some of the pro-inflammatory effects of complement arise from
      intrinsic tissue synthesis of donor C3, and that this may represent a previously
      unrecognized source of tissue injury. The occurrence of local synthesis of C3 of
      donor allotype may have functional implications related to C3 allotype, and may
      also be relevant to strategies to inhibit intrarenal complement-mediated injury.

PMID- 7737279
TI  - Antigen presentation by Leishmania mexicana-infected macrophages: activation of
      helper T cells specific for amastigote cysteine proteinases requires
      intracellular killing of the parasites.
AB  - Leishmania mexicana amastigotes proliferate in the phagolysosomes of mammalian
      macrophages. The parasites abundantly synthesize lysosomal cysteine proteinases,
      which are encoded by the lmcpb gene family. One of these genes was overexpressed
      in Escherichia coli, and the purified recombinant protein was used as an antigen
      to induce and establish a T helper 1 (Th1) cell line. The T cells recognize
      epitopes shared by the native cysteine proteinases and the recombinant protein.
      Infected bone marrow-derived macrophages induced to express major
      histocompatibility complex class II molecules by interferon (IFN)-gamma do not
      affect parasite viability. These macrophages fail to stimulate the proliferation
      of the T cell line. In contrast, strong T cell stimulation is observed after the
      parasites are killed by treatment with L-leucine methylester, or after activation
      of macrophages by IFN-gamma and tumor necrosis factor-alpha. It is concluded that
      infected macrophages efficiently present this lysosomal Leishmania antigen once
      the parasites are inactivated and degraded. This observation may be of
      considerable relevance for the outcome of Leishmania infections provided that it
      can be extended to other parasite antigens.

PMID- 7737280
TI  - Follicular dendritic cells and B cell chemotaxis.
AB  - B cells isolated from germinal centers (GC) of immune mice 2-5 days after antigen
      (Ag) challenge migrate in response to chemotactic signals, whereas GC B cells
      isolated at other times and resting B cells do not. Since B cells are in direct
      contact with follicular dendritic cells (FDC) in GC we reasoned that FDC might
      play a role in enabling B cells to become chemotactically active. Resting B cells
      were co-cultured with FDC either with or without anti-mu-dextran (anti-mu-dex) as
      an Ag surrogate and/or recombinant interleukin (rIL)-4 as a T cell surrogate.
      After 3 days, the B cells were isolated and their migration to chemotactic
      factors contained in zymosan-activated serum assessed in microchemotaxis
      chambers. B cells incubated alone or with anti-mu-dex or rIL-4 showed minimal
      migration, which could be increased if both anti-mu-dex or rIL-4 were present.
      However, maximal migration was obtained when B cells were cultured with FDC, and
      this was not increased by addition of anti-mu-dex and/or rIL-4, indicating that
      the FDC signal was a primary signal and did not require pre-activation of the B
      cells. Checkerboard analysis using variation in concentration and location of the
      chemoattractant in chemotaxis chambers indicated that both chemotaxis and
      chemokinesis occurred. B cell migration began within 6 h of culture, peaked by 48
      h and decreased thereafter. Removal of FDC or interference with FDC-B cell
      contact ablated or significantly decreased induction of B cell migration.
      Furthermore, induction did not require functional T cells. These data indicate
      that FDC can induce resting B cells to become responsive to chemotactic signals.

PMID- 7737281
TI  - Activation of virus-specific major histocompatibility complex class II-restricted
      CD8+ cytotoxic T cells in CD4-deficient mice.
AB  - Acute enteritic or respiratory disease is a consequence of coronavirus infection
      in man and rodents. Mouse hepatitis virus, stain A59 (MHV-A59) causes acute
      hepatitis in mice and rats and induces a response of major histocompatibility
      complex (MHC) class II-restricted CD4+ cytotoxic T cells, protecting mice against
      acute infection. In the present study we show that MHV-A59 infection of mice that
      lack a functional CD4 gene activates effector cells of the CD8+ phenotype. These
      cytotoxic T cells lyse virus-infected target cells in a MHC class II-restricted
      fashion. The results indicate that CD8+ T cells have the potential to utilize MHC
      class II as restriction element, illustrating that the immune system can
      effectively deal with evading microorganisms, such as viruses which down-regulate
      MHC class I.

PMID- 7737282
TI  - The protein defective in X-linked agammaglobulinemia, Bruton's tyrosine kinase,
      shows increased autophosphorylation activity in vitro when isolated from cells in
      which the B cell receptor has been cross-linked.
AB  - X-linked agammaglobulinemia is a primary inherited immunodeficiency resulting in
      a lack of or dramatic reduction in the number of mature B lymphocytes and, thus,
      greatly reduced levels of serum immunoglobulin. The defect results from mutations
      in the gene for Bruton's tyrosine kinase (Btk). Using rabbit antisera generated
      against Btk, we have demonstrated an increase in the level of in vitro kinase
      activity present in anti-Btk immunoprecipitates from B cells following
      stimulation with anti-immunoglobulin antibody. This increase in immune complex
      kinase activity is detectable 1 to 2 min following stimulation and remains
      elevated for over 30 min. A similar increase was not seen with two late pre-B
      cell lines investigated in the same way. This stimulation of activity may suggest
      a role for Btk in signalling through the B cell receptor or associated proteins,
      in mature B cells.

PMID- 7737283
TI  - Activation of murine epidermal gamma delta T cells through surface 2B4.
AB  - Dendritic epidermal T cells (DETC) are gamma delta T cells that normally reside
      in murine skin. They express on their surface the 2B4 molecule, a 66-kDa
      glycoprotein of the immunoglobulin gene superfamily thought to be associated with
      anti-tumor cytotoxicity by natural killer and lymphokine-activated killer cells.
      Here, we show that ligation of surface 2B4 transduces cell activation signals in
      DETC. Treatment with anti-2B4 monoclonal antibodies triggers the secretion of
      interferon-gamma and interleukin-2 by DETC lines, induces proliferation of
      resting DETC lines, amplifies anti-CD3-dependent proliferation of DETC freshly
      isolated from mouse skin; and up-regulates egr-1 and c-fos mRNA expression. These
      results indicate a unique pathway for DETC activation.

PMID- 7737285
TI  - Interleukin-10 differentially regulates cytokine inhibitor and chemokine release
      from blood mononuclear cells and fibroblasts.
AB  - In this study we have examined the effects of interleukin-10 (IL-10) on blood
      mononuclear cells (MNC) and on skin as well as on synovial fibroblasts. In
      unstimulated MNC, we found that IL-10 is a potent stimulator of interleukin-1
      receptor antagonist (IL-1ra) and monocyte chemoattractant protein-1 (MCP-1)
      production and an inhibitor of IL-8 release. In cells exposed to IL-1 beta, it
      also moderately stimulated IL-1ra production and release of soluble tumor
      necrosis factor receptor p75 (sTNF-R p75) and inhibited IL-8 and MCP-1
      production. In addition, we have evidence that the biological effects of IL-10
      are not restricted to hematopoietic cells. IL-10 stimulated sTNF-R p55 dose
      dependently and inhibited MCP-1 release from IL-1 beta-activated fibroblasts,
      whereas IL-8 production was not affected. Taken together, these findings identify
      novel biological actions of IL-10 on blood mononuclear and connective tissue
      cells which support its regulatory functions as a suppressor of inflammatory
      processes.

PMID- 7737284
TI  - Glycosylphosphatidylinositol-linked Db does not induce an influenza-specific
      cytotoxic T lymphocyte response or recycle membrane-bound peptides.
AB  - Major histocompatibility complex (MHC) class I molecules, as well as MHC class I
      bound peptides, are known to recycle between the cell surface and an undefined,
      endosomal-like compartment. Little is known about the functional significance of
      this process. We have explored this using two different forms of the H-2Db
      molecule expressed in transgenic mice, either transmembranous (Db-tm) or with a
      glycophosphatidylinositol (GPI)-lipid anchor (Db-GPI). The recycling capacity of
      peptides bound to Db-tm and Db-GPI was investigated using glycosylated Db-binding
      glycopeptides, which were detected by flow cytometry. Only the tm form of Db was
      found to readily internalize and recycle glycopeptides to the cell surface. When
      transgenic mice were immunized with influenza A virus (PR8) strain and tested for
      cytotoxic T lymphocyte (CTL) responses against an immunedominant nucleoprotein
      epitope (366-374, ASNENMETM), only Db-tm mice were found to generate specific CTL
      responses. The results support the idea that membrane recycling of MHC class I
      bound peptides on antigen-presenting cells may be important for the generation of
      certain CTL responses.

PMID- 7737286
TI  - Analysis of the fine specificity of rat, mouse and human TAP peptide
      transporters.
AB  - Prior to their association with major histocompatibility complex (MHC) class I
      molecules, peptides generated from cytosolic antigens need to be translocated by
      the MHC-encoded peptide transporter (TAP) into the lumen of the endoplasmic
      reticulum (ER). While class I molecules possess well-known binding
      characteristics for peptides, the fine specificity of TAP for its peptide
      substrates has not been analyzed in detail. Previously, we have studied the
      effect of amino acid variations at the N-terminal, the C-terminal, and the
      penultimate residue on the efficiency of peptide translocation. Using
      permeabilized cells, we have shown that TAP pre-selects peptides in an allele-
      and species-specific manner, for which only the C-terminal residue is crucial.
      This finding is confirmed in the present study by using microsomes containing
      different TAP. The influence of amino acid substitutions at positions 2 to 7 of 9
      residue model peptides on TAP-dependent peptide translocation is systematically
      examined. Only a few amino acid substitutions at these positions affect the
      efficiency of peptide translocation significantly, e.g. Pro at position 2 or 3
      negatively influences transport whereas Glu at positions 6 and 7 enhances
      transport. The differences in translocation by the rat TAP alleles a or u, mouse
      TAP and human TAP are, however, minor for the peptide with internal substitutions
      used in this study. These results show that the C-terminal residue essentially
      governs the species-specific substrate specificity of TAP.

PMID- 7737287
TI  - Cytokines and clinical gene therapy.

PMID- 7737288
TI  - Simple strategy to induce antibodies of distinct specificity: application to the
      mapping of gp120 and inhibition of HIV-1 infectivity.
AB  - In this study 96 15-mer peptides encompassing the entire sequence of HIV-1 gp120
      were synthesized and used to immunize BALB/c mice (i) alone or (ii) in
      conjunction with the T helper cell determinant FISEAIIHVLHSR (FIS) from sperm
      whale myoglobin, which is well recognized by major histocompatibility complex
      (MHC) class II molecules of BALB/c. Of these peptides 39 were immunogenic per se
      and 57 were not. Out of the 57 non-immunogenic peptides 53 could be rendered
      immunogenic with the second immunization protocol. With the exception of 4 cases,
      the anti-peptide antibody titers induced in (ii) were equal (14 cases) or higher
      (78 cases) than those induced in (i). From the 96 anti-peptide antibodies tested,
      12 were able to recognize recombinant gp120 with good antibody titers, a result
      in agreement with previously identified B cell epitopes from gp120 by anti
      peptide antibodies induced with longer peptides conjugated to a carrier protein.
      Moreover, 4 of the 12 anti-peptide antisera that recognized gp120 were able to
      neutralize HIV-1 infectivity in vitro, showing that the strategy of co
      immunization with FIS may afford functional antibodies.

PMID- 7737289
TI  - T cells expressing the gamma delta T cell receptor are not required for egg
      granuloma formation in schistosomiasis.
AB  - Immunopathology in schistosomiasis consists of a granulomatous response around
      parasite eggs. It has been established that granuloma formation is mediated by
      CD4+ T helper cells. However, the role of T cells bearing the gamma delta T cell
      receptor (TCR) has not been determined. In this study we utilized mutant mice
      that lack either alpha beta or gamma delta T cells as a result of gene targeting
      to investigate the relative roles of alpha beta and gamma delta T cells in the
      induction of immunopathology related to schistosomiasis. Mutant and control mice
      were infected with Schistosoma mansoni and granuloma formation as well as lymph
      node cell proliferative responses to egg antigens were analyzed after 8 weeks.
      TCR delta mutant mice (lacking gamma delta T cells) displayed vigorous formation
      of egg granulomas that were not significantly different from those observed in
      normal controls, both in terms of granuloma size and cellular composition. In
      contrast, TCR alpha and TCR beta mutant mice (lacking alpha beta T cells) were
      unable to form granulomas. Moreover, mesenteric lymph node cells from TCR delta
      mutant and control mice responded strongly to egg antigens in vitro, while TCR
      alpha and beta mutant mice did not. Our studies show that in schistosomiasis
      granuloma formation and proliferative responses to egg antigens are strictly
      dependent on alpha beta T cells. They also suggest that gamma delta T cells by
      themselves can neither mediate a granulomatous inflammation, nor significantly
      modify one mediated by alpha beta T cells.

PMID- 7737290
TI  - Regulation of interferon-gamma mRNA in a cytolytic T cell clone: Ca(2+)-induced
      transcription followed by mRNA stabilization through activation of protein kinase
      C or increase in cAMP.
AB  - Activation pathways inducing the expression of the interferon (IFN)-gamma gene in
      a cytotoxic T lymphocyte (CTL) clone were studied for their effects on
      transcription and on mRNA stability. IFN-gamma was secreted by the CTL clone in
      response to the Ca2+ ionophore ionomycin when used in conjunction with either
      protein kinase C (PKC)-activating phorbol 12-myristate 13-acetate (PMA) or with
      agents increasing cAMP, including prostaglandin E2. We describe that ionomycin
      induced IFN-gamma gene transcription, which was totally inhibited in the presence
      of cyclosporin A (CSA), an immunosuppressant forming a calcineurin-inhibiting
      complex with cyclophilin. Ionomycin did not, however, permit accumulation of IFN
      gamma mRNA. Activation of PKC by PMA or of cAMP-dependent protein kinase through
      increase in cAMP had no transcription-inducing effect, either alone or in
      conjunction with ionomycin, as measured in run on assays of the IFN-gamma gene.
      When transcription of the IFN-gamma gene, initiated in the presence of ionomycin
      and an agent increasing intracellular cAMP, was inhibited by CSA in the absence
      of PKC or cAMP-dependent protein kinase activation, the IFN-gamma mRNA was
      rapidly degraded (half-life = 30 min). When either PKC was activated or
      intracellular cAMP was increased at the time of inhibition with CSA, a
      stabilizing effect was observed on IFN-gamma mRNA, which led to an increase in
      secreted IFN-gamma. These effects were selective, they did not affect the rate of
      transcription of the actin gene, nor the accumulation of actin mRNA. These
      results show that (i) post-transcriptional events can be critical for IFN-gamma
      expression in activated lymphocytes, and (ii) specific stabilization of IFN-gamma
      mRNA can be mediated by activation of two different protein kinases involved in T
      cell activation.

PMID- 7737291
TI  - Intrathymic T cell receptor (TcR) targeting in mice lacking CD4 or major
      histocompatibility complex (MHC) class II: rescue of CD4 T cell lineage without
      co-engagement of TcR/CD4 by MHC class II.
AB  - A critical step during intrathymic T cell development, termed positive selection,
      is associated with rescue of short-lived, immature thymocytes from programmed
      cell death, T cell lineage commitment, and induction of lineage-specific
      differentiation programs. T cell receptor (TcR)-major histocompatibility complex
      (MHC) interactions during positive selection can be closely mimicked by targeting
      TcR on immature thymocytes to cortical epithelial cells in situ via hybrid
      antibodies. Here, we show that antibody-mediated TcR signaling in mice deficient
      for CD4 or MHC class II expression induces polyclonal differentiation of the CD4
      T cell lineage. Following a single TcR signal pulse in situ, a temporal sequence
      of phenotype changes can be discerned: CD69 up-regulation (< 1 day), CD8 down
      regulation, TcR up-regulation (1-1.5 days) and down-regulation of the heat-stable
      antigen (1.5-2 days). Differentiation of phenotypically and functionally mature
      CD4 T cells in situ is attained within 3 days. Rescue of CD4 lineage T cells in
      the absence of TcR/CD4 co-engagement by MHC class II in this experimental system
      supports the stochastic/selective model of T cell lineage commitment.

PMID- 7737292
TI  - Identification of a major T cell immunogen in the anti-schistosome response of
      adult residents in an area endemic for Schistosoma mansoni.
AB  - Vaccine-induced immunity to Schistosoma mansoni infection depends on the specific
      priming of certain T cell subsets and on the recall of this response by natural
      infections months or years after vaccine administration. Thus, those schistosome
      proteins that activate T cells in individuals stimulated by natural infections
      are potential candidate vaccine antigens. In the present study, we identified and
      purified one such T cell-stimulating antigen and evaluated its immunological
      properties in subjects living in an area endemic for Schistosoma mansoni.
      Chromatography fractions (gel filtration, followed by ion exchange
      chromatography) of soluble extracts of schistosomula were screened for their
      ability to stimulate schistosome-specific T cell clones derived from a subject
      sensitized by natural infection. A fraction stimulating most clones was
      identified and characterized. A few nanograms of this fraction, containing a
      major 9-10-kDa component, stimulated the T helper cells of most adults living in
      an endemic area of Brazil, and was able to trigger a strong cutaneous immediate
      hypersensitivity reaction. In contrast, children reacted weakly to this antigen
      preparation both in blastogenesis and in skin tests, although they mounted a
      significant reaction to crude larval antigen preparations. In conclusion, this
      work identifies a schistosomula antigen that induces a strong T cell response in
      adults sensitized by natural infections. This T cell response develops gradually
      in children and adolescents, is apparently not restricted by the HLA haplotypes
      common in the study area, and allows the production of parasite-specific IgE
      antibodies. Thus, this T cell response has some features of the immune response
      that is believed to protect chronically exposed humans from reinfection.

PMID- 7737293
TI  - In the absence of major histocompatibility complex class II molecules, invariant
      chain is translocated to late endocytic compartments by autophagy.
AB  - It has been suggested that the cytoplasmic amino-terminal tail of invariant chain
      (Ii) contains a sorting signal that directs trafficking of the major
      histocompatibility complex (MHC) class II: Ii oligomeric complex to endocytic
      compartments. This model is based, in part, on the observation that in the
      absence of MHC class II molecules, Ii is detectable in lysosomal structures, a
      phenotype that is dependent on an intact NH2 terminus. However, the route by
      which Ii gains access to endosomal compartments in the absence of class II
      molecules remains uncertain. Here we report a mechanism that localizes Ii in
      lysosomal compartments independently of class II. We show that murine Ii can be
      detected by immunofluorescence within late endocytic compartments of stably
      transfected Ltk- mouse fibroblasts. Immunochemical studies indicate that
      degradation of Ii in these cells is sensitive to the lysosomotropic agent
      ammonium chloride, yet the majority of Ii that undergoes this apparent lysosomal
      degradation is sensitive to the enzyme endoglycosidase H. This finding suggests
      that Ii may reach the lysosomal compartment by a route that bypasses the Golgi
      complex. Consistent with this possibility, we found that in contrast to Ii which
      is complexed to class II molecules, transport of free Ii to lysosomes is
      prevented by 3-methyladenine, an inhibitor of the autophagic pathway of protein
      degradation, a process which involves direct transport from the endoplasmic
      reticulum to lysosomes. These data suggest the route of transport that leads to
      endosomal localization of Ii in the absence of class II is distinct from that
      taken when expressed with class II. This forces a re-evaluation of the concept
      that the cytosolic tail of Ii contains a dominant Golgi-to-endosomal sorting
      signal.

PMID- 7737294
TI  - Interactions between the tyrosine kinases p56lck, p59fyn and p50csk in CD4
      signaling in T cells.
AB  - Interaction of the CD4 co-receptor with major histocompatibility complex (MHC)
      class II molecules during antigen presentation results in enhancement of antigen
      receptor signaling. The synergism between the two receptors is believed to result
      from the juxtaposition of the CD4-associated tyrosine kinase p56lck with the
      cytoplasmic domains of CD3 complex components. Here, we report that cross-linking
      of CD4 on the surface of Jurkat cells using monoclonal antibodies results in
      activation of the CD3-associated kinase p59fyn. Co-cross-linking of CD4 and CD3
      results in synergistic activation of p59fyn. The p59fyn kinase is also
      hyperactive in a Jurkat cell line stably transfected with a constitutively active
      p56lck mutant, indicating that p56lck mediates CD4 activation of p59fyn. In
      support of this hypothesis, expression of a dominant inhibitory mutant of p59fyn
      blocks CD4 signals involved in gene activation. In addition, the p59fyn dominant
      inhibitor mutant blocks gene-activating signals induced by expression of a
      constitutively active mutant of p56lck. Overexpression of the regulatory kinase
      p50csk, which attenuates TcR signaling by inactivation of p59fyn, inhibits
      signaling from the constitutively active form of p56lck. Taken together, these
      data suggest that CD4/p56lck enhancement of TcR signaling is, at least in part,
      mediated by activation of p59fyn, and may be regulated by p50csk.

PMID- 7737295
TI  - Gene structure and chromosomal localization of the mouse homologue of rat OX40
      protein.
AB  - The OX40 protein is expressed only on activated rat CD4+ T blasts and is a member
      of a superfamily of cell surface molecules which includes CD40, CD30, CD95 (Fas),
      CD27, 4-1BB antigens and the receptors for tumor necrosis factor (TNF) and nerve
      growth factor (NGF). The proteins of this group are related to each other by
      having three to six repeats of a cysteine-rich sequence in their extracellular
      domains. Members of this family of receptors have also been shown to bind to
      ligands which are structurally related to TNF. The mouse homologue of the rat
      OX40 protein was cloned at the cDNA and genomic levels. The gene structure shows
      that there are several intron/exon borders shared between OX40 and CD27, CD40,
      TNF receptor type I, CD95 and 4-1BB genes. This group of genes is less closely
      related structurally to the gene structure of the NGF receptor. The gene encoding
      murine OX40 has been placed on mouse chromosome 4, in an area which contains the
      genes for TNF receptor type II and 4-1BB, and is syntenic with a region of human
      chromosome 1 which contains human TNF receptor type II, OX40, and CD30 genes.

PMID- 7737296
TI  - Differential expression of type I insulin-like growth factor receptors in
      different stages of human T cells.
AB  - Insulin-like growth factor I (IGF-I) has been implicated to play a regulatory
      role in T cell development and in T cell function. We investigated the expression
      of type I IGF receptors on human peripheral T cells related to the maturation and
      activation stage using the type I IGF receptor-specific monoclonal antibody alpha
      IR3. It appeared that 87% of the CD4+CD45RA+ cells and 66% of the CD8+CD45RA+
      cells were alpha IR3+, whereas only 37% of the CD4+CD45R0+ cells and 38% of the
      CD8+CD45R0+ cells bound alpha IR3. We also found that the fraction of alpha IR3+
      cells within in vivo or in vitro activated (HLA-DR+) T cells is markedly lower
      than in nonactivated (HLA-DR-) cells. In vitro phytohemagglutinin-activated T
      cells and CD4+CD45R0+ cells activated with recall antigens also contained less
      alpha IR3+ cells (1-6%) than nonactivated cells (30-54%).

PMID- 7737297
TI  - Regulation of the p70zap tyrosine protein kinase in T cells by the CD45
      phosphotyrosine phosphatase.
AB  - Two classes of protein tyrosine kinases (PTK) are utilized by the T cell antigen
      receptor (TcR)/CD3 complex for initiation of the signaling cascade, the Src
      family PTK p56lck and p59fyn, and the Syk-family PTK p70zap and p72syk. In
      addition, the CD45 phosphotyrosine phosphatase (PTPase) is required for the
      induction of tyrosine phosphorylation by the TcR/CD3, presumably by positively
      regulating Src-family PTK. Here we report that CD45 also regulates the Syk-family
      PTK p70zap (or ZAP-70). In CD45-negative T cells, p70zap was constitutively
      phosphorylated on tyrosine and co-immunoprecipitated with the TcR-zeta chain. In
      resting wild-type CD45-positive cells, p70zap was mainly unphosphorylated, but it
      was rapidly phosphorylated on tyrosine upon treatment of the cells with anti-CD3
      or PTPase inhibitors. Finally, p70zap co-distributed with CD45 in intact T cells,
      and tyrosine phosphorylated p70zap was dephosphorylated by CD45 in vitro. These
      findings suggest that CD45 plays an important role, direct or indirect, in the
      regulation of p70zap and its function in TcR/CD3 signaling.

PMID- 7737299
TI  - Immunoglobulins from rats that are resistant to adjuvant arthritis suppress the
      disease in arthritis-susceptible rats.
AB  - The therapeutic effect of high doses of polyclonal immunoglobulins has been well
      established in various B cell-associated autoimmune diseases. In the present work
      we have examined the effect of low doses of immunoglobulins in adjuvant
      arthritis, a T cell-associated disease in the Lewis rat. Lewis rats were treated
      with purified rat immunoglobulins as well as their Fc and F(ab')2 fragments and
      their protective effect on adjuvant arthritis was evaluated. We found that early
      as well as late treatment with low doses of rat immunoglobulins induced
      refractoriness to disease induction. The effect was found to be carried out by
      the F(ab')2 part of the immunoglobulins and could be adsorbed by affinity
      purification on Mycobacterium tuberculosis. The protective antibodies were
      present in Fisher and BN rats that are resistant to adjuvant arthritis, but not
      in the arthritis susceptible Lewis and Wistar strains. We suggest that resistance
      to autoimmune arthritis is associated with the presence of protective
      immunoglobulins and that their effect is carried out through the antigen
      recognition part of the molecule.

PMID- 7737298
TI  - Nitric oxide up-regulates the release of inflammatory mediators by mouse
      macrophages.
AB  - Nitric oxide (NO) plays a key role in mediating macrophage cytotoxicity towards
      different targets, including tumoral cells and intracellular pathogens. However,
      its role in macrophage immunoregulation is less well defined. In this study, we
      have investigated the effect of altering NO levels on the production by mouse
      macrophages of cytokines, and reactive oxygen intermediates as measured by
      luminol-dependent chemiluminescence. Our results demonstrate that NO can enhance
      the release of both tumor necrosis factor-alpha and interleukin-1 alpha, and
      chemiluminescence. Thus, in addition to acting as a powerful effector molecule in
      mediating cytotoxic activities of mouse macrophages, NO can play a role in
      enhancing the production of a variety of other inflammatory mediators, and thus
      can contribute both directly and indirectly to the immunopathology of macrophage
      dependent inflammation.

PMID- 7737300
TI  - Intranasal immunization with liposomes induces strong mucosal immune responses in
      mice.
AB  - BALB/c mice were immunized intranasally with either soluble ovalbumin (OVA) or
      OVA entrapped in liposomes. The effect of adding Sigma cholera toxin B subunit
      (sCT-B), which contained low amounts of cholera holotoxin (CT), or recombinant CT
      B (rCT-B) which was free from CT, as mucosal adjuvants was also investigated. The
      mucosal [lung enzyme-linked immunospot assay (ELISPOT), lung washing] and
      systemic (serum antibody and spleen ELISPOT) responses of immunized mice to OVA
      and CT-B were determined. Results showed that soluble OVA and liposome-entrapped
      OVA were poor inducers of mucosal or systemic responses unless CT-B was added as
      adjuvant. The types of responses augmented by sCT-B and rCT-B were different. CT
      B containing low levels of CT (i.e. sCT-B) boosted both mucosal and systemic IgA
      and IgG responses, whereas rCT-B only increased IgG responses, unless antigen was
      entrapped in liposomes. Although rCT-B was unable to adjuvant IgA responses
      against soluble OVA, it was able to induce IgA responses against itself. These
      data show that mucosal responses can be increased by addition of CT-B containing
      low levels of CT to antigen preparations given intranasally, suggesting a direct
      role for CT-A in isotype switching. Furthermore, the ability of CT-B to adjuvant
      IgA responses against added antigens and its ability to induce responses against
      itself appear to be separate phenomena. The results from this study should assist
      the rational formulation of mucosal vaccines which induce potent mucosal and
      systemic immune responses.

PMID- 7737301
TI  - Measles virus-induced down-regulation of CD46 is associated with enhanced
      sensitivity to complement-mediated lysis of infected cells.
AB  - CD46, the major component of the measles virus (MV) receptor complex and a member
      of the regulators of complement activity (RCA) gene cluster, is down-regulated in
      MV-infected cells. We investigated whether the reduction of surface CD46
      correlates with enhanced sensitivity of lymphoid and monocytic cells to lysis by
      activated complement. On human U937 cells, acutely or persistently infected with
      MV-Edmonston (ED) vaccine strain, infection-dependent down-regulation of CD46
      confers sensitivity to activated complement, regardless of the pathway of
      activation and the specificity of the activating antibodies. Interestingly, down
      regulation of CD46 alone is sufficient to confer susceptibility of cells to
      complement lysis despite the continued surface expression of other RCA proteins
      such as CD35 and CD55. In primary cultures, both peripheral blood lymphocytes and
      macrophages are efficiently lysed in the presence of complement activated via the
      alternative pathway after MV infection. In contrast to the MV-ED infection,
      infection of cells with the lymphotropic MV wild-type strain WTF does not down
      regulate CD46. Cells infected with MV-WTF do not exhibit enhanced susceptibility
      to complement lysis. These data suggest that MV strains similar to WTF that do
      not down-regulate CD46 may have an enhanced potential for replication and
      dissemination within the human host, whereas complement-mediated elimination of
      cells infected with CD46-down-regulating strains of MV, such as ED, may limit the
      spread of MV infection, and could thus represent an attenuating factor for MV.

PMID- 7737302
TI  - Chronic relapsing experimental autoimmune encephalomyelitis with a delayed onset
      and an atypical clinical course, induced in PL/J mice by myelin oligodendrocyte
      glycoprotein (MOG)-derived peptide: preliminary analysis of MOG T cell epitopes.
AB  - Myelin basic protein (MBP) and proteolipid protein (PLP), the most abundant
      proteins of central nervous system (CNS) myelin, have been extensively studied as
      possible primary target antigens in multiple sclerosis (MS), a primary
      demyelinating autoimmune disease of the CNS. However, there is increasing
      evidence to suggest that autoimmune reactivity against the quantitatively minor
      myelin component, myelin oligodendrocyte glycoprotein (MOG), can also play a role
      in the pathogenicity of MS. We recently demonstrated a predominant response to
      MOG by peripheral blood lymphocytes from patients with MS tested for their
      reactivity against various myelin antigens, including MBP and PLP. To ascertain
      whether or not T cell reactivity to MOG in MS is a potentially pathogenic
      response, we have tested the ability of synthetic MOG peptides (pMOG)
      representing potential T cell epitopes, to induce neurological disease in mice.
      Both strains of mice tested (SJL/J and PL/J mice) were able to mount a primary T
      cell response to some of the five MOG peptides synthesized, pMOG 1-21, 35-55, 67
      87, 104-117 and 202-218. T cell lines could be raised in both strains to pMOG 35
      55 and 67-87, but epitope definition revealed that each strain recognized a
      different minimal epitope within these two peptides. T cell lines to pMOG 1-21
      and 202-218 could also be raised in SJL/J and PL/J mice, respectively. T cell
      reactivity to pMOG 104-117 was not observed in either mouse strain. None of the
      peptides tested induced detectable clinical signs in SJL/J mice. In contrast, an
      MS-like chronic relapsing-remitting disease could be induced in PL/J mice with
      pMOG 35-55. The disease presented with a delayed onset and with clinical signs
      which differed significantly in their progression and expression from the typical
      ascending paralysis of experimental autoimmune encephalomyelitis induced with
      other myelin components, such as MBP and PLP. Histological examination of CNS
      tissue from mice injected with pMOG 35-55 revealed only mild neuropathological
      signs with few inflammatory foci in brain and spinal cord. Some myelin splitting
      and edema were detected upon electron microscopic examination in the spinal cord
      and cerebellum. Transfer of pMOG 35-55 reactive T cells into naive PL/J mice
      resulted in pathological changes characterized by inflammatory foci in the brain
      and spinal cord. This passively induced disease was clinically silent, as was
      also reported for Lewis rats injected with T cells specific for the same MOG
      peptide.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7737303
TI  - Transforming growth factor-beta inhibits interleukin-12-induced production of
      interferon-gamma by natural killer cells: a role for transforming growth factor
      beta in the regulation of T cell-independent resistance to Toxoplasma gondii.
AB  - Severe-combined immune deficient (SCID) mice have been found to resist infection
      with the intracellular protozoan parasite Toxoplasma gondii via interleukin (IL)
      12 stimulation of interferon (IFN)-gamma production by natural killer (NK) cells.
      Previously, we demonstrated the presence of increased levels of transcripts for
      transforming growth factor-beta (TGF-beta) in the brains and lungs of SCID mice
      infected with T. gondii, leading us to investigate the role of TGF-beta in the
      mechanism of resistance to T. gondii in these mice. Stimulation of splenocytes
      from SCID mice with heat-killed T. gondii resulted in production of low levels of
      IFN-gamma and a two to threefold increase in levels of TGF-beta in the culture
      supernatants. Production of IFN-gamma in these cultures was increased three to
      fourfold by addition of anti-TGF-beta antibody. Stimulation of splenocytes from
      SCID mice with IL-12 in combination with either TNF-alpha or IL-1 beta resulted
      in production of high levels of IFN-gamma. Addition of TGF-beta to these cultures
      inhibited production of IFN-gamma in a dose-dependent manner. Immunohistochemical
      studies revealed increased levels of TGF-beta protein in the spleens of SCID mice
      5 days after oral infection with the ME49 strain of T gondii, and brains of SCID
      mice at 18 days post-infection. However, no difference was detected in the levels
      of TGF-beta transcripts in the spleens of uninfected mice or mice infected for 5
      days. To test whether TGF-beta could antagonize IL-12 mediated resistance to T.
      gondii in vivo, we administered TGF-beta to SCID mice infected with T. gondii.
      This treatment resulted in earlier mortality of infected mice and significantly
      reduced the ability of exogenous IL-12 to delay time-to-death. Administration of
      anti-TGF-beta to SCID mice, beginning 24 h prior to infection and every 2 days
      thereafter, delayed significantly time-to-death. Together, our data demonstrate
      that TGF-beta antagonizes the ability of IL-12 to stimulate production of IFN
      gamma by splenocytes from SCID mice, and suggest a role for TGF-beta in
      regulation of T cell-independent resistance to T. gondii.

PMID- 7737304
TI  - Stimulation of bicarbonate secretion by alpha- and beta-adrenoceptor agonists in
      rat caecum in vitro.
AB  - This study examines the effects of adrenergic drugs on bicarbonate secretion by
      the rat caecum in vitro. Noradrenaline, phenylephrine but not clonidine,
      stimulated secretion in a concentration-related manner. Noradrenaline responses
      were antagonised by alprenolol (20 microM) but not phentolamine (10 microM)
      whilst phenylephrine was antagonised by phentolamine (10 microM), prazosin (5
      microM) but not yohimbine (5 microM), alprenolol or tetrodotoxin (1 microM).
      Replacement of mucosal Cl- abolished the phenylephrine response. Combined
      stimulation with maximum concentrations of phenylephrine and isoprenaline gave a
      response which was not greater than that to either agonist alone but it did
      involve both alpha- and beta-adrenoceptors as judged from the effects of
      alprenolol and phentolamine either alone or combined. Submaximum concentrations
      of the two agonists did show additive responses. The results show that alpha 1-
      but not alpha 2-adrenoceptor agonists stimulate bicarbonate secretion and may act
      on the same transport mechanism as beta-adrenoceptor agonists. Noradrenaline
      stimulates via beta-adrenoceptors.

PMID- 7737305
TI  - Alpha 1-adrenoceptor-mediated sympathetically dependent mechanical hyperalgesia
      in the rat.
AB  - The model of rolipram (a type IV phosphodiesterase inhibitor) induced
      prolongation (> 3 days) of the mechanical hyperalgesia produced by the
      intradermal injection of prostaglandin E2 in the hairy skin of the hindpaw of the
      rat, measured by the Randall-Selitto paw-withdrawal test, was employed to study
      mechanisms involved in the contribution of the sympathetic postganglionic neuron
      to mechanical hyperalgesia. Lumbar surgical sympathectomy prevented rolipram
      induced prolongation of prostaglandin E2 hyperalgesia. Decentralization of
      sympathetic postganglionic neurons innervating the hindpaw did not, however,
      effect rolipram-induced prolongation of prostaglandin E2 hyperalgesia.
      Phentolamine, an alpha-adrenoceptor antagonist, and prazosin, an alpha 1
      selective adrenoceptor antagonist, when given systemically or intradermally at
      the site of injection of prostaglandin E2 and rolipram, blocked rolipram-induced
      prolongation of prostaglandin E2 hyperalgesia. Intrathecal administration of
      phentolamine and prazosin were, however, without effect on rolipram-induced
      prolongation of prostaglandin E2 hyperalgesia. Yohimbine, an alpha 2-adrenoceptor
      antagonist given systemically, intradermally or intrathecally also did not
      produce any alteration in rolipram-induced prolongation of prostaglandin E2
      hyperalgesia. We propose that sympathetic postganglionic neurons are involved in
      rolipram-induced prolongation of prostaglandin E2 hyperalgesia and that this form
      of sympathetically dependent hyperalgesia, which is independent of activity in
      preganglionic sympathetic neurons, is mediated by a peripheral alpha 1-adrenergic
      mechanism.

PMID- 7737306
TI  - Antibronchospastic activity of MEN10,627, a novel tachykinin NK2 receptor
      antagonist, in guinea-pig airways.
AB  - The antibronchospastic activity against acetylcholine, antigen, histamine plus
      platelet-activating factor (PAF) or the selective tachykinin neurokinin (NK)1 and
      NK2 receptor agonists of the novel tachykinin NK2 receptor antagonist, MEN10,627
      (cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2 beta-5 beta)), was studied in anesthetized
      guinea-pigs. MEN10,627 (30-100 nmol/kg i.v.) reduced in a dose-dependent manner
      the bronchospasm induced by the tachykinin NK2 receptor agonist [beta
      Ala8]neurokinin A-(4-10) and the effect of the highest dose lasted up to 5 h from
      its administration. Conversely, airway constriction induced by the NK1 receptor
      agonist [Sar9]substance P sulfone or acetylcholine was unaffected by MEN10,627 up
      to a dose of 3 mumol/kg i.v. In animals sensitized with ovalbumin and pretreated
      with the endopeptidase inhibitor phosphoramidon, the aerosolized antigen produced
      a bronchospasm which was inhibited by MEN10,627 (30-100 nmol/kg i.v.) but not by
      the tachykinin NK1 receptor antagonist, (+/-)-CP96,345 ([2R,3R-cis- and [2S,3S)
      cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1- azabicyclo[2.2.2]octan-3
      amine]) (3 mumol/kg i.v.). Both MEN10,627 (30-100 nmol/kg i.v.) and (+/-)
      CP96,345 (30-300 nmol/kg i.v.) reduced the PAF-induced hyperresponsiveness to
      histamine, without affecting the hypotension induced by PAF or the bronchospasm
      induced by histamine in guinea-pigs not exposed to PAF, showing the involvement
      of both tachykinin NK1 and NK2 receptors in this model. In summary, MEN10,627
      behaves as a potent, selective and long-lasting tachykinin NK2 receptor
      antagonist in vivo. Further, tachykinin NK2 receptors could be activated during
      allergic responses and in the development of airway hyperresponsiveness.

PMID- 7737307
TI  - Effects of glucocorticoids and beta-adrenoceptor agonists on the proliferation of
      airway smooth muscle.
AB  - An increase in airway smooth muscle is a characteristic feature of asthma.
      Because beta-adrenoceptor agonists and corticosteroids are commonly used in the
      treatment of asthma we have studied the effects of these medicines on the growth
      of airway smooth muscle. These agents were incubated with bovine airway smooth
      muscle cells for 40 h for measurement of thymidine incorporation and 64 h for
      measurement of cell counts. Salbutamol inhibited thymidine incorporation (IC50 =
      60 nM) and led to a reduction in cell number (IC50 = 10 nM). At 10 microM there
      was a 14.6 +/- 2.6% reduction in cell number. Salmeterol also inhibited the
      growth of the airway smooth muscle cells but the effect did not plateau at 10
      microM. At this concentration there was an 89.5 +/- 3.6% reduction in thymidine
      incorporation and a 44.1 +/- 5.2% reduction in cell number. Cortisol and
      beclomethasone dipropionate were more potent than salbutamol in inhibiting
      thymidine incorporation with IC50 values of 5 nM and 0.2 nM respectively.
      Cortisol 100 nM led to a 16.6 +/- 6.5% reduction and beclomethasone dipropionate
      3 nM led to a 17.8 +/- 5.8% reduction in cell number. If similar effects occur in
      man and in vivo, these medicines could act directly on airway smooth muscle to
      inhibit the development of hyperplasia.

PMID- 7737308
TI  - A selective CCKB receptor antagonist potentiates, mu-, but not delta-opioid
      receptor-mediated antinociception in the formalin test.
AB  - The endogenous peptides enkephalins and cholecystokinin appear to play an
      opposite role in the control of pain. In this work, the effect of the selective
      CCKB receptor antagonist PD-134,308 on antinociceptive effects induced by
      morphine or by a complete inhibitor of enkephalin-metabolizing enzymes, RB 101,
      was studied using the formalin test. In mice, s.c. injection of formalin into the
      dorsal surface of the hindpaw had a biphasic effect: an early nociceptive
      response followed by a late response. Morphine (2 mg/kg i.p.) caused naloxone
      (0.5 mg/kg s.c.) but not naltrindole (0.5 mg/kg s.c.) reversible antinociceptive
      responses in the early and late phases of the assay, suggesting a preferential
      involvement of mu-opioid receptors in these responses. In contrast, RB 101 (50
      mg/kg i.p.) produced antinociceptive effects in the early and late phases which
      were both antagonized by the delta-selective opioid receptor antagonist
      naltrindole (0.5 mg/kg s.c.). The antinociceptive response elicited by morphine
      on the late but not the early phase of the formalin test was potentiated by the
      CCKB antagonist PD-134,308 (1 mg/kg i.p.). This compound was unable to facilitate
      the analgesic effects produced by RB 101 on both phases, in contrast to what was
      observed in the hot plate test with mice and the tail flick test with rats.
      Therefore, in the formalin test with mice, the facilitating effects of opiate
      induced analgesia by CCKB receptor antagonists seem to be restricted to mu-opioid
      receptor-mediated responses.

PMID- 7737309
TI  - The inhibitory mechanisms of nicorandil in isolated rat urinary bladder and
      femoral artery.
AB  - Nicorandil or cromakalim inhibited contractile responses to acetylcholine and KCl
      in detrusor muscles of rat urinary bladder, whereas nitroglycerin inhibited only
      the responses to acetylcholine. In the detrusor muscles contracted by electrical
      stimulations, relaxations caused by nicorandil and cromakalim were inhibited by
      glyburide, but not by nitroglycerin or apamin. Methylene blue slightly
      potentiated the nicorandil-relaxation without affecting the cromakalim
      relaxation. NG-Monomethyl-L-arginine also did not affect the relaxation induced
      by nicorandil. The level of cGMP was increased by both nicorandil and
      nitroglycerin. In rat femoral arteries contracted by phenylephrine, the
      relaxation induced by nicorandil was inhibited by methylene blue, glyburide and
      apamin. The relaxation induced by cromakalim was inhibited by glyburide, but not
      by apamin or methylene blue. These results suggest that the effect of nicorandil
      is due to activation of KATP channels in rat detrusor muscles and is due to the
      activation of guanylate cyclase, KATP and KCa channels in rat femoral arteries.
      The effect of cromakalim is due to the activation of KATP channels in both smooth
      muscles.

PMID- 7737310
TI  - Inhibition of food passage by omeprazole in the chicken.
AB  - The effect of omeprazole, a proton pump inhibitor, on the forward passage of the
      crop contents of chicks receiving 20% medium chain or long chain triacylglycerol
      was studied. Medium chain triacylglycerol significantly delayed the crop emptying
      of chicks compared with long chain triacylglycerol. Omeprazole also significantly
      inhibited passage from the crop of the long chain triacylglycerol meal.
      Application of omeprazole induces achlorhydria and consequently hypergastrinemia
      but chicken gastrin lower than 100 nmol/kg did not delay crop emptying. The
      addition of hydrochloric acid (HCl) to the diet reversed the action of omeprazole
      on the crop emptying of chicks. We conclude, then, that omeprazole delayed the
      crop emptying in chicks as a consequence of inhibition of acid secretion,
      although the mediator is not gastrin.

PMID- 7737311
TI  - Differential Fos-protein induction in rat forebrain regions after acute and long
      term haloperidol and clozapine treatment.
AB  - Both acute and long-term effects of haloperidol and clozapine on Fos-like
      immunoreactive nuclei in several rat forebrain areas were quantified. Rats were
      treated with saline (1 ml/kg.day, control), haloperidol (1 mg/kg.day) and
      clozapine (20 mg/kg.day) i.p. for 21 days. Two hours before perfusion fixation a
      single (acute treatment) or last (long-term treatment) dose of the drug was
      given. Drug-induced catalepsy and gain in body weight were also measured. A
      single dose of haloperidol produced large increases in Fos-like immunoreactive
      nuclei in the striatum, the nucleus accumbens and central amygdala. Following
      long-term treatment these increases were reduced in all nuclei studied, except
      the lateral septum. Acute clozapine treatment had slight (if any) effects on the
      number of Fos-like immunoreactivity-expressing nuclei in the striatum, but the
      increases in the nucleus accumbens, the lateral septum, the paraventricular and
      supraoptic nuclei of the hypothalamus and the central amygdala were substantial.
      Long-term clozapine treatment reduced the acute response significantly in all the
      areas except the nucleus accumbens. Both haloperidol and clozapine treatment
      reduced the weight gain of the rats. Haloperidol, but not clozapine, induced
      catalepsy that remained maximal during the long-term haloperidol treatment. These
      results indicate that in most brain areas high Fos-protein levels are not
      necessary to maintain antipsychotic activity or side-effects. The persisting
      effect of clozapine in the nucleus accumbens may be of significance to the
      efficacy of this drug in treatment-refractory schizophrenia.

PMID- 7737312
TI  - Intraperitoneal administration of baclofen increases consumption of both solid
      and liquid diets in rats.
AB  - It has previously been demonstrated that systemic administration of the GABAB
      receptor agonist baclofen increases food intake but decreases water intake in
      rats. In the present study, the effects of baclofen (2-4 mg/kg i.p.) were
      investigated on food intake in non-deprived rats given access to either pelleted
      food (n = 8) or a palatable liquid diet (n = 8). Baclofen (2-4 mg/kg i.p.)
      significantly increased the consumption of both the pelleted and the liquid
      foods. The increased intake of the liquid diet (i) argues against the involvement
      of non-specific gnawing in the increased consumption of the solid food by
      baclofen, and (ii) suggests that the inhibition of water intake produced by
      baclofen is not due to interference with the mechanical aspects of drinking, such
      as licking on a drinking spout, or the swallowing of liquid.

PMID- 7737313
TI  - Blockade of morphine tolerance by ACEA-1328, a novel NMDA receptor/glycine site
      antagonist.
AB  - Recent studies indicate that competitive and non-competitive NMDA receptor
      antagonists can block the development of morphine tolerance. Since glycine is
      considered to be a co-agonist for activation of NMDA receptors we examined the
      effect of a novel bioavailable NMDA receptor/glycine site antagonist, 5-nitro-6,7
      dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328), on the development of
      morphine tolerance. Administration of ACEA-1328 (20 mg/kg) completely blocked
      tolerance to morphine-induced antinociception in the tail flick test in CD-1
      mice, without affecting the basal nociceptive response or potentiating morphine
      induced antinociceptive effects. These data suggest that inhibition of NMDA
      receptor activity via blockade of the glycine co-agonist site is potentially
      viable as a therapeutic approach for preventing development of morphine
      tolerance.

PMID- 7737314
TI  - Glutathione protects against hypoxic/hypoglycemic decreases in 2-deoxyglucose
      uptake and presynaptic spikes in hippocampal slices.
AB  - The effects of glutathione, its analogue: YM737 (N-(N-gamma-L-glutamyl-L-
      cysteinyl) glycine l-isopropyl ester sulfate monohydrate), a monoester of
      glutathione, and N-acetyl-L-cysteine on hypoxia/hypoglycemia-induced decreases in
      CA1 presynaptic fiber spikes and 2-deoxyglucose uptake were investigated using
      rat hippocampal slices. The drugs were added to normal medium for 30 min before
      the incubation under hypoxic/hypoglycemic conditions (20 min), and, after a 3-h
      washout, presynaptic potential or 2-deoxyglucose uptake in hippocampal slices was
      measured. Treatment with glutathione, YM737 and N-acetyl-L-cysteine produced an
      attenuation of the hypoxia/hypoglycemia-induced decrease in presynaptic fiber
      spikes and 2-deoxyglucose uptake. The order of potency for neuroprotective action
      was YM737 > or = N-acetyl-L-cysteine > glutathione. The present results suggest a
      role for glutathione in improving hypoxia/hypoglycemia-induced dysfunction of
      hippocampal regions.

PMID- 7737315
TI  - Alterations in plasma and brain amino acids after administration of the
      glycine/NMDA receptor partial agonist, D-cycloserine, to mice and rats.
AB  - The NMDA/glycine receptor partial agonist, D-cycloserine, has recently been
      reported to exert anticonvulsant effects in different seizure models in mice and
      rats. In view of the high doses (> 100 mg/kg) needed for these effects, actions
      other than those mediated by the glycine site might be involved. In this respect,
      inhibition of pyridoxal phosphate-dependent enzymes involved in amino acid
      metabolism might play a role. In the present experiments, D-cycloserine was
      administered at an anticonvulsant dose (320 mg/kg) to mice and rats and levels of
      11 amino acids, including several neurotransmitters, were determined in brain
      cortex and plasma at different times after administration. In addition, the
      concentration of D-cycloserine was determined in plasma and brain. Compared to
      peak concentrations of D-cycloserine in plasma, only about 20% of D-cycloserine
      appeared in the brain. The only marked alteration in brain amino acids was an
      increase in alanine levels, while amino acids acting as neurotransmitters were
      hardly altered. The data indicate that the anticonvulsant action of D-cycloserine
      is not secondary to changes in levels of amino acid neurotransmitters.

PMID- 7737316
TI  - The human vas deferens: correlation of response pattern to noradrenaline and
      histological structure.
AB  - Specimens of human vas deferens were studied histologically and by measuring
      changes in response to adrenoceptor agonists. In intact tissues noradrenaline
      induced both lengthening and shortening responses which were identified with
      contractions of circular and longitudinal muscle respectively. The agonists
      phenylephrine or methoxamine evoked mainly shortening but little lengthening. The
      tissues were unresponsive to clonidine or isoprenaline. Longitudinal strips but
      not rings responded reliably to phenylephrine and to caffeine. The lengthening
      responses of intact specimens to noradrenaline were relatively insensitive to the
      antagonist phenoxybenzamine. In contrast both shortening and lengthening
      responses were inhibited by prazosin or phentolamine but not by idazoxan. A
      physiological function for the predominance of muscle types in different
      specimens is proposed. A pharmacological selectivity for the muscle types by
      alpha 1-selective adrenoceptor agonists and by phenoxybenzamine is discussed and
      the clinical implication considered.

PMID- 7737317
TI  - Different kinetics of tolerance to behavioral and electroencephalographic effects
      of chlordiazepoxide in the rat.
AB  - The daily oral administration of chlordiazepoxide (40 mg/kg) over 9 weeks in rats
      elicited full tolerance to muscle relaxant effects within 7 weeks, as revealed by
      twice weekly evaluations of abdominal tone myorelaxation and decreased grip
      strength. No full tolerance was achieved, however, during the 9 weeks of
      treatment in terms of ataxia. Electroencephalographic (EEG) studies showed that
      this tolerance to the behavioural effects was accompanied by a progressive
      decrease in mean power spectra, associated with a progressive decrease in the
      beta band, but in this case, full tolerance was reached within 4 weeks. Once
      weekly evaluations of the ability of chlordiazepoxide to protect the animals
      against pentylenetetrazole seizures revealed a similar pattern. Treatment with
      flumazenil (50 mg/kg p.o.) 24 h after the last chlordiazepoxide administration
      induced a clear withdrawal syndrome associated with EEG changes which consisted
      of an increase in total power spectra associated with an increase in the delta
      band (in comparison with chlordiazepoxide-dependent rats not given the
      antagonist). These findings suggest that the different kinetics of the tolerance
      to anticonvulsant and EEG effects in comparison to myorelaxant effects can be
      attributed to a different involvement of benzodiazepine receptor subtypes.

PMID- 7737318
TI  - Pharmacological properties of NK433, a new centrally acting muscle relaxant.
AB  - The pharmacological properties of NK433 ((-)-(R)-2-methyl-3-(1-pyrrolidinyl)-4'
      trifluoromethylpropiophenone+ ++ monohydrochloride), a novel muscle relaxant,
      were investigated. NK433 inhibited intercollicular decerebrate rigidity (gamma
      rigidity) and anemic decerebrate rigidity (alpha-rigidity) dose dependently.
      NK433 was stronger in inhibiting gamma-rigidity than alpha-rigidity. NK433
      inhibited the increase in muscle spindle discharges induced by pinna pinching
      (gamma-activity) without affecting muscle spindle discharges or neuromuscular
      transmission. At muscle relaxant doses in decerebrate rigidities, NK433 did not
      affect the muscle tone induced by morphine-HCl nor that of normal animals. These
      results suggest that NK433 selectively depresses the excessive muscle tone of
      decerebrate rigidities through its effects on the central nervous system, and
      inhibition of gamma-activity causes a preferential depression of gamma-rigidity
      in comparison to alpha-rigidity. In i.v. experiments, the effects of NK433 on
      decerebrate rigidities were similar to those of eperisone-HCl and tolperisone
      HCl, but in p.o. experiments, NK433 was at least 3 times as potent as eperisone
      HCl and tolperisone-HCl.

PMID- 7737319
TI  - Modafinil and cortical gamma-aminobutyric acid outflow. Modulation by 5
      hydroxytryptamine neurotoxins.
AB  - The acute or chronic administration of modafinil, (diphenyl-methyl-sulfinyl-2
      acetamide, 30 mg/kg s.c.) decreased gamma-amino-butyric acid (GABA) outflow from
      the cerebral cortex of freely moving guinea pigs and rats. In 5,7
      dihydroxytryptamine intracerebroventricularly pretreated guinea pigs, the effect
      of modafinil on GABA outflow was reversed and the noradrenaline cortical levels
      increased. Prazosin (35.8 ng/kg i.p.) blocked the drug-induced increase in GABA
      efflux. In vitro experiments, performed in rat cortical slices, showed that
      modafinil failed to affect [3H]GABA release and uptake as well as glutamic acid
      decarboxylase activity. In conclusion, our results suggest that the balance
      between central noradrenaline and 5-hydroxytryptamine transmission is important
      for the regulation by modafinil of the GABAergic release in the cerebral cortex.

PMID- 7737320
TI  - Role of alpha 1-adrenoceptors and 5-HT2 receptors in serotonin-induced
      contraction of rat prostate: autoradiographical and functional studies.
AB  - Urinary obstruction from benign prostatic hyperplasia is a common clinical
      problem possibly associated with excessive prostatic constriction around the
      urethra. These studies compared adrenergic and serotonergic functional activity
      to specific alpha 1 and serotonin (5-hydroxytryptamine; 5-HT) binding sites in
      the rat prostate. Isolated, left ventral lobes of the rat prostate were removed
      and examined for in vitro contraction. Norepinephrine-induced contraction of the
      rat prostate was competitively blocked by prazosin with an apparent antagonist
      dissociation constant (pKB) of 8.13. 5-HT also contracted the rat prostate.
      However, in the presence of prazosin, maximum 5-HT contraction was reduced by
      half suggesting that high concentrations of 5-HT can activate alpha 1 receptors
      in the prostate. The concentration-response curve to 5-HT in the presence of 1
      microM prazosin was competitively inhibited by the 5-HT2 receptor antagonist
      LY53857 (6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid 2-hydroxyl-1
      methylpropylester (Z)-2-butenedioate (1:1)) (pKB = 9.02). Autoradiographic
      studies with [125I]LSD (2-iodo-lysergic acid diethylamide) documented the
      presence of 5-HT2 receptors since significant displacement of the radioligand
      occurred with 5-HT and LY53857, but not with prazosin. The alpha 1-adrenoceptor
      ligand [125I]HEAT ([beta-(4-hydroxy-3-iodophenyl)ethylaminomethyl]-tetralone)
      confirmed the presence of alpha 1-adrenoceptors in the rat prostate since
      significant displacement of the radioligand occurred with prazosin, but not 5-HT
      or LY53857. The inability of prazosin to displace [125I]LSD and the inability of
      5-HT to displace [125I]HEAT suggest that 5-HT cannot directly interact with alpha
      1-adrenoceptors in the prostate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737321
TI  - Stimulation of glutamate receptors in the intermediate/caudal striatum induces
      contralateral turning.
AB  - The aim of the present study was to investigate the role of striatal NMDA,
      kainate and AMPA receptors in the turning behaviour of rats. N-methyl-D-aspartate
      (NMDA, 500 ng/0.5 microliters), kainic acid (50 ng/0.5 microliters) or alpha
      amino-3-hydroxy-5-methyl-4-isoxasole- propionic acid (AMPA, 1000 ng/0.5
      microliters), injected into the intermediate and caudal parts of the caudate
      putamen, induced contralateral head turns and rotations. This effect was delayed
      or was not observed after administration of the compounds into the globus
      pallidus. The antagonist of non-NMDA receptors, 6,7-dinitroquinoxaline-2,3-dione
      (DNQX, 1000 ng/0.5 microliter), antagonized the contralateral head turns and
      rotations induced by AMPA (1000 ng/0.5 microliter) or kainic acid (50 ng/0.5
      microliter), and evoked per se (2000 ng/0.5 microliter) the ipsilateral head
      turns and rotations. The NMDA receptor antagonist, (+/-)-2-amino-5
      phosphonopentanoic acid (AP5, 1000 ng/0.5 microliter), induced mainly ipsilateral
      head turns and rotations; when injected in a dose of 500 ng/0.5 microliters, it
      inhibited the contralateral head turns and rotations after NMDA. The results seem
      to suggest that the contralateral head turns and rotations induced by stimulation
      of NMDA, AMPA and kainate receptors in the intermediate and caudal parts of the
      caudate-putamen may result from activation of the gamma-aminobutyrate (GABA)
      ergic strionigral pathway.

PMID- 7737322
TI  - Anorectic effect of metformin in obese Zucker rats: lack of evidence for the
      involvement of neuropeptide Y.
AB  - The hypothalamic neuropeptide Y content and preproneuropeptide Y mRNA expression
      were studied in metformin-treated (300 mg/kg orally for 12 days), in pair-fed and
      in ad libitum-fed obese Zucker rats in order to elucidate possible mechanisms
      involved in the anorectic and body weight reducing effect of chronic metformin
      treatment in genetically obese Zucker rats. In addition the acute influence of
      metformin on food intake was studied by comparing its effects after oral and
      parenteral administration. The concentration of neuropeptide Y in the
      hypothalamic paraventricular nucleus was significantly higher in the metformin
      treated and pair-fed rats when compared to the control animals. The expression of
      preproneuropeptide Y mRNA in the arcuate nucleus was similar in all three
      treatment groups. Both chronic metformin treatment and pair-feeding markedly
      lowered hyperinsulinaemia in these animals. A single subcutaneous dose of
      metformin (300 mg/kg) reduced food intake only in obese animals, while the same
      dose of metformin given orally did not affect food intake in either lean or obese
      animals. It is concluded that the treatment with metformin and pair-feeding,
      which results in comparable reductions in food intake, body weight gain and
      hyperinsulinaemia, similarly increase neuropeptide Y concentrations in the
      paraventricular nucleus while not affecting preproneuropeptide Y mRNA expression
      in the arcuate nucleus. The increase in hypothalamic neuropeptide Y content may
      be secondary to the reduction in hyperinsulinaemia during metformin treatment and
      pair-feeding. Thus, the anorectic effect of chronic metformin treatment cannot be
      explained by changes in content or expression of hypothalamic neuropeptide Y.

PMID- 7737323
TI  - Modulation of the clozapine structure increases its selectivity for the dopamine
      D4 receptor.
AB  - Clozapine has a more marked affinity for the recently cloned dopamine D4 receptor
      than for the dopamine D2 receptor. In the search for a selective ligand for the
      dopamine D4 receptor, useful as a pharmacological tool or as a potent atypical
      antipsychotic, a pyridobenzodiazepine derivative bioisoster of clozapine, JL 18,
      8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido [2,3-b][1,4]benzodiazepine, was
      found to be the most dopamine D4-selective ligand belonging to the diarylazepine
      class. Indeed, JL 18 binds to the dopamine D4 receptor with affinity up to 25
      times superior to that for the dopamine D2 receptor and presents reduced
      affinities for other receptors.

PMID- 7737324
TI  - Murine macrophage cell lines contain mu 3-opiate receptors.
AB  - Opiate alkaloid-selective, opioid peptide-insensitive mu 3 receptors are present
      in three murine macrophage cell lines (J774.2; RAW 264.7; BAC1.2F5). The receptor
      binds morphine, its active metabolite morphine 6-glucuronide and certain other
      alkaloids, but not morphine 3-glucuronide or any of the opioid peptides tested.
      The cell lines thus provide valuable model systems for investigation of mu 3
      opiate receptors, previously demonstrated to mediate inhibitory effects of
      morphine on activation of human peripheral blood macrophages (monocytes).

PMID- 7737325
TI  - Phospholipase A2 activation is not required for long-term synaptic depression.
AB  - Low-frequency synaptic stimulation evokes long-term depression of synaptic
      strength. One hypothesis is that modification of AMPA receptors by phospholipase
      A2 causes long-term depression. A previous study reported bromophenacylbromide, a
      completely nonselective phospholipase A2 inhibitor, blocked long-term depression
      at Schaffer collateral-CA1 synapses in hippocampus. In contrast, I show here that
      3-(4-octadecyl)-benzoylacrylic acid (OBAA), a much more potent and selective
      inhibitor of low and high molecular weight phospholipase A2, does not block long
      term depression at these same synapses, indicating that phospholipase A2 is not
      necessary for modifications causing long-term depression.

PMID- 7737326
TI  - Effects of 5-HT receptor antagonists on morphine-induced tolerance in mice.
AB  - The effect of 5-HT receptor antagonists on tolerance to morphine antinociception
      was studied in mice. Slow release morphine suspension was injected subcutaneously
      (s.c.) in order to produce tolerance. When different doses of morphine (3, 6 and
      9 mg/kg) were administered on the 4th day after injection of slow-release
      morphine suspension, tolerance to the test doses of morphine was observed. The
      tolerance obtained was decreased by pretreatment with the non-selective 5-HT
      receptor antagonist methysergide (1 and 2 mg/kg) or the 5-HT2 receptor antagonist
      ritanserin (1 and 2 mg/kg). When the 5-HT receptor antagonists were used on the
      2nd and 3rd day after injection of slow-release morphine suspension or on the 4th
      day (60 min before last dose of morphine), a maximum reduction in morphine
      tolerance was observed on the 3rd day. Pretreatment of animals with metergoline
      (1 and 2 mg/kg) or mianserin (1 and 2 mg/kg) also decreased the tolerance to
      morphine. It may be concluded that at least a 5-HT2 receptor mechanism is
      involved in tolerance to morphine antinociception.

PMID- 7737327
TI  - Effects of a synthetic rat adrenomedullin on regional hemodynamics in rats.
AB  - The effects of rat adrenomedullin, a novel vasorelaxant peptide, on systemic and
      regional hemodynamics were examined in conscious Sprague Dawley (SD) rats and
      spontaneously hypertensive rats (SHR). The intravenous infusion of adrenomedullin
      at rates of 1.67 and 5 micrograms/kg per min decreased the mean arterial pressure
      in a dose-dependent fashion in both types of rats. Adrenomedullin at a rate of 5
      micrograms/kg per min increased the heart rate and cardiac output. As a result,
      the total peripheral resistance significantly decreased. With regards to the
      regional hemodynamics, adrenomedullin significantly increased the flow rates in
      the lungs, heart, spleen, kidneys, adrenal glands and small intestine of SHR. The
      flow rates in the brain and skin did not change and the flow rates in the
      skeletal muscle and testis were decreased. These regional hemodynamic changes
      were also observed in SD rats and there was no qualitative difference in the
      regional responses to adrenomedullin between SHR and SD rats. Thus,
      adrenomedullin predominantly increased the flow rates in organs in which
      adrenomedullin gene was highly expressed. It therefore seems that adrenomedullin
      may act as a local vasodilatory hormone rather than as a circulatory hormone.

PMID- 7737328
TI  - Effects of tolcapone, a novel catechol-O-methyltransferase inhibitor, on striatal
      metabolism of L-dopa and dopamine in rats.
AB  - In vivo brain microdialysis was used to assess the effects of tolcapone, a novel
      central and peripheral inhibitor of catechol-O-methyltransferase on striatal 3,4
      dihydroxyphenyl-L-alanine (L-dopa) and dopamine metabolism. The oral
      administration of 30 mg/kg of tolcapone failed to change dopamine output but
      elicited a marked and long-lasting decrease of the extracellular levels of
      homovanillic acid (HVA) and 3-methoxytyramine with a concomitant increase of 3,4
      dihydroxyphenylacetic acid (DOPAC). The administration of L-dopa (20 and 60 mg/kg
      p.o.) + benserazide (15 mg/kg p.o.) resulted in dose-dependent increase of
      dialysate levels of L-dopa and 3-O-methyl-DOPA. Tolcapone (30 mg/kg p.o.), given
      as adjunct to both doses of L-dopa, markedly enhanced the elevation or
      extracellular L-dopa, while it completely prevented the formation of 3-O-methyl
      DOPA. In another experiment, the administration of L-dopa + benserazide (30 + 15
      mg/kg p.o.) resulted in increased extracellular levels of dopamine, DOPAC, HVA
      and 3-methoxytyramine. The co-administration of tolcapone (30 mg/kg p.o.) further
      increased dopamine and DOPAC levels, whereas HVA and 3-methoxytyramine effluxes
      were reduced. These findings support the notion that tolcapone has the ability to
      enhance striatal dopamine neurotransmission by increasing L-dopa bioavailability
      through peripheral and central inhibition of L-dopa O-methylation, as well as by
      blocking the central conversion of dopamine into 3-methoxytyramine.

PMID- 7737329
TI  - Activation of both dopamine D1 and D2 receptors necessary for amelioration of
      conditioned fear stress.
AB  - Mice exhibited a marked suppression of motility when they were re-placed in the
      same environment in which they had previously received an electric footshock.
      This psychological stress-induced motor suppression, known as conditioned fear
      stress, was dose dependently attenuated by apomorphine, a non-selective dopamine
      receptor agonist. Combined treatment with the dopamine D1 receptor agonist, SKF
      38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1-H-3-benzazepine), and the
      dopamine D2 receptor agonist, quinpirole, also synergistically attenuated the
      conditioned fear stress although, alone, neither SKF 38393 nor quinpirole did so
      at the doses used. The effects of apomorphine and of the coadministration of SKF
      38393 and quinpirole on the conditioned fear stress were completely blocked by
      the dopamine D1 receptor antagonist, SCH 23390 (R-(+)-7-chloro-8-hydroxy-3-methyl
      1-phenyl-2,3,4,5-tetrahydro-1H- 3-benzazepine), and by the dopamine D2 receptor
      antagonist, (-)-sulpiride. These results suggest that a dysfunction in the
      dopaminergic neuronal system is responsible for the conditioned fear stress, and
      that the activation of both dopamine D1 and D2 receptors is necessary to
      attenuate this stress-induced motor suppression.

PMID- 7737330
TI  - Cross-tolerance to ethanol and gamma-hydroxybutyric acid.
AB  - In the present study, the development of tolerance to the motor impairing effects
      of gamma-hydroxybutyric acid (GHBA) and ethanol was compared (Experiment 1). Rats
      were required to perform a motor coordination task daily shortly after ethanol
      (3.5 g/kg) and GHBA (1.0 g/kg) administration for 9 consecutive days. Tolerance
      to the motor impairing effects of ethanol and GHBA developed to a similar extent
      but with different patterns. On the tenth day, the presence of cross-tolerance to
      the motor impairing effects of GHBA and ethanol was assessed (Experiment 2).
      Administration of 1.0 g/kg GHBA produced a significantly lower impairment in
      ethanol-tolerant rats than in ethanol-naive rats. Similarly, administration of
      3.5 g/kg ethanol induced a significantly lower impairment in GHBA-tolerant rats
      than in GHBA-naive rats. The presence of cross-tolerance between GHBA and ethanol
      is discussed in terms of common pathways of neuroadaptation to chronic GHBA and
      ethanol.

PMID- 7737331
TI  - Effects of desipramine and alprazolam on forced swimming behaviour of adult rats
      exposed to prenatal diazepam.
AB  - Pregnant rats were treated with a single daily s.c. injection of diazepam (2
      mg/kg) over gestation days 14-20. This treatment led to a reduction in GABA
      receptor complex function since adult male offspring showed a strong decrease in
      electrographic hippocampal responses to alprazolam and a strongly increased
      response to picrotoxin after intra-locus coeruleus injection of the two
      compounds. No difference in immobility time in the forced swimming test and in
      spontaneous motor activity was observed between prenatally vehicle- and diazepam
      exposed offspring. Conversely, prenatal exposure to diazepam potentiated the anti
      immobility effect of subchronic desipramine (10 mg/kg i.p.) and made active a
      dose of desipramine (5 mg/kg i.p.) that was ineffective in prenatally vehicle
      exposed rats. This effect was observed only in pretested rats. Prenatal exposure
      to diazepam blocked the anti-immobility effect of subchronic alprazolam (15 mg/kg
      i.p.) in both non-pretested and pretested rats. Spontaneous motor activity was
      strongly reduced in all groups. These findings suggest that a persistent
      reduction in GABA receptor complex function, induced by prenatal exposure to
      diazepam, does not alter the mobility of adult progeny in the forced swimming
      test, but it may have consequences when drugs acting on the GABA receptor complex
      are used.

PMID- 7737332
TI  - Acute dopaminergic influence on plasma adrenaline levels in the rat.
AB  - This study was aimed at in vivo characterisation of the possible role of dopamine
      receptors in the modulation of adrenaline release from the adrenal medulla in
      rats. Quinpirole (0.3, 1 and 3 mg/kg s.c., 30 min), an agonist at dopamine D2
      like receptors induced a statistically significant increase not only in adrenal
      dopamine but also in plasma and heart adrenaline levels. The effects of the
      lowest dose of quinpirole were blocked by domperidone (5 mg/kg s.c., 150 min).
      Implantation of catheters followed by blood sampling appeared to be a stressful
      procedure, inducing itself an elevation of adrenal dopamine and of heart
      adrenaline by 100 and 250%, respectively. To explore the possibility of
      determining the plasma levels of adrenaline without blood sampling, regression
      modelling was performed by means of partial least squares regression (PLS) using
      treatment and levels of heart adrenaline and adrenal dopamine as predictor
      variables. The selected variables were found to be good predictors of plasma
      adrenaline levels. Accordingly, the increase in adrenal dopamine and heart
      adrenaline levels following administration of the dopamine autoreceptor agonist,
      talipexole, and the classical non-selective dopamine receptor agonist,
      apomorphine, were interpreted as indicators of the increased adrenomedullary
      adrenaline release. Neither of the dopamine D2 receptor antagonists used, i.e.
      domperidone, supposed to have only peripheral effects, nor raclopride, had
      significant effects on adrenal dopamine and heart adrenaline. Our results support
      the presence of peripherally located dopamine D2-like receptors, capable of
      acutely stimulating not only the synthesis of catecholamines, but also the
      release of adrenaline from adrenals in the conscious rat.

PMID- 7737333
TI  - The gamma-aminobutyric acid uptake inhibitor, tiagabine, is anticonvulsant in two
      animal models of reflex epilepsy.
AB  - The effects of i.p. administration of the gamma-aminobutyric acid (GABA) uptake
      inhibitors R(-)N-(4,4-di(3-methylthien-2-yl)-but-3-enyl) nipecotic acid
      hydrochloride (tiagabine; molecular weight 412.0), (1-(2-(((diphenylmethylene)
      amino)oxy)ethyl)-1,2,5,6-tetrahydro-3- pyridinecarboxylic acid hydrochloride (NNC
      711; molecular weight 386.9), and (+/-)-nipecotic acid (molecular weight 128.2)
      are compared with those of carbamazepine (molecular weight 236.3) on sound
      induced seizures and locomotor performance in genetically epilepsy-prone (GEP)
      rats. The ED50 value against clonic seizures (in mumol kg-1 at the time of
      maximal anticonvulsant effect) for tiagabine was 23 (0.5 h), and for NNC-711 was
      72 (1 h), and for carbamazepine was 98 (2 h). (+/-)-Nipecotic acid (0.4-15.6 mmol
      kg-1) was not anticonvulsant. High doses of NNC-711 (207-310 mumol kg-1) and of
      (+/-)-nipecotic acid (39-78 mmol kg-1) induced ataxia and myoclonic seizures 0.25
      1 h. Tiagabine and carbamazepine did not induce myoclonic seizures and had
      similar therapeutic indices (locomotor deficit ED50/anticonvulsant ED50) ranging
      from 0.4 to 1.9. In Papio papio, we observed a reduction in photically induced
      myoclonic seizures with tiagabine (2.4 mumol kg-1 i.v.) accompanied with
      neurological impairment. Tiagabine has comparable anticonvulsant action to
      carbamazepine in rats and has anticonvulsant effects in non-human primates
      supporting the potential use of inhibitors of GABA uptake as therapy for
      epilepsy.

PMID- 7737334
TI  - The selective 5-HT2A receptor antagonist, MDL 100,907, increases dopamine efflux
      in the prefrontal cortex of the rat.
AB  - Diminished function within the mesocortical dopamine system has been to
      hypothesized to contribute directly to the negative and indirectly to the
      positive symptoms of schizophrenia. Based on the proposed role of 5-HT2 receptor
      blockade in the antipsychotic profile of clozapine and its preferential
      augmentation of prefrontal dopamine release, we have examined the effects of the
      selective 5-HT2A receptor antagonist, R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4
      fluorophenyl)ethyl]-4-piperidi ne- methanol (MDL 100,907), on dopamine release in
      the rat medial prefrontal cortex using in vivo microdialysis. The results
      indicate that local 5-HT2A receptors exert a tonic inhibitory influence on
      dopamine efflux in the medial prefrontal cortex. These observations are
      consistent with the hypothesis that 5-HT2A receptor blockade contributes to the
      unique antipsychotic profile of clozapine and that MDL 100,907 may have
      antipsychotic activity.

PMID- 7737335
TI  - Protective effect of DS-4574, a peptidoleukotriene receptor antagonist, against
      endotoxin-induced intestinal injury in rats.
AB  - We evaluated the protective effect of DS-4574 (6-(2-cyclohexylethyl)
      [1,3,4]thiadiazolo[3,2-a]-1,2,3- triazolo[4,5-d]pyrimidin-9(3H)-one), a
      peptidoleukotriene receptor antagonist, against intestinal mucosal injury evoked
      by endotoxin in rats by exploring changes in hematocrit and plasma leakage along
      with morphological features. Treatment with Escherichia coli endotoxin (5 mg/kg
      i.v.) alone elicited hemoconcentration, vasocongestion and a marked mucosal
      necrosis. DS-4574 (10-50 mg/kg) effectively prevented these changes on either
      oral or intraduodenal administration. These results demonstrate that
      peptidoleukotrienes may be key mediators in the intestinal injury induced by
      endotoxin in rats.

PMID- 7737336
TI  - Antagonists of the metabotropic glutamate receptor do not prevent induction of
      long-term potentiation in the dentate gyrus of rats.
AB  - The effects of two competitive metabotropic glutamate (mGlu) receptor
      antagonists, (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) and (S)-4
      carboxylphenylglycine (4CPG), were studied on long-term potentiation in the
      dentate gyrus of rats under urethane anaesthesia. Intracerebroventricular
      (i.c.v.) injection of MCPG or 4CPG 30 min prior to tetanic stimulation of the
      perforant path in rats did not affect the induction of long-term potentiation
      measured by extracellular recording. As a control, i.c.v. injections of the NMDA
      receptor antagonist, dl(-)-2-amino-5-phosphonopentanoic (dl-AP5), effectively
      blocked long-term potentiation. These results suggest that the mGlu receptor
      subtype blocked by MCPG and 4CPG is not involved in long-term potentiation in the
      dentate gyrus.

PMID- 7737337
TI  - Effects of inhibitors of cGMP-dependent protein kinase in atrial heart and aortic
      smooth muscle from rats.
AB  - Several activators of cGMP-dependent protein kinase (protein kinase G) such as 8
      Br-cGMP reduced force of contraction in rat left atria. Inhibitors of protein
      kinase G antagonized the negative inotropic effect of 8-Br-cGMP but not of
      acetylcholine in atria. However, the acetylcholine-induced relaxation in aortic
      rings was significantly inhibited by protein kinase G inhibition. It is concluded
      that the reduction by 8-Br-cGMP of force of contraction in atria is related to
      activation of protein kinase G. In response to acetylcholine, activation of
      protein kinase G is probably a major step in smooth muscle relaxation but is not
      involved in the reduction of force of contraction in atria.

PMID- 7737338
TI  - Pentylenetetrazole-induced parasympathetic blood flow increase in the lower lip
      of the cat.
AB  - The pentylenetetrazole (30 mg/kg i.v.)-induced blood flow increase in cat lip was
      more marked on the sympathectomized side than on the intact side (P < 0.01). This
      difference is probably dependent on the degree of simultaneous activation of the
      sympathetic nerve elicited by pentylenetetrazole administration. The blood flow
      increases were markedly suppressed by prior treatment with hexamethonium (10
      mg/kg i.v.), an autonomic ganglion blocker (P < 0.01). Combined section of the
      facial and glossopharyngeal nerve roots completely abolished the blood flow
      increases elicited by pentylenetetrazole administration (P < 0.01), but section
      of either the facial or glossopharyngeal nerve root alone failed to produce
      complete abolition (P < 0.05). These results indicate that the relevant
      parasympathetic vasodilator fibers originate not only from the glossopharyngeal,
      but also the facial nerves and that both participate in pentylenetetrazole
      induced vasodilatation in the cat lower lip.

PMID- 7737339
TI  - Vinpocetine is as potent as phenytoin to block voltage-gated Na+ channels in rat
      cortical neurons.
AB  - The effects of vinpocetine and phenytoin on voltage-gated Na+ channels were
      examined on cultured cerebrocortical neurones of the rat using a conventional
      whole-cell patch-clamp method. Vinpocetine and phenytoin decreased Na+ currents
      in a concentration-dependent manner, with IC50 values of 44.2 +/- 14.6 and 50.5
      +/- 17.4 microM, respectively. Both compounds shifted the voltage dependence of
      the steady-state inactivation of the channel in the hyperpolarising direction.
      This pronounced Na+ channel blocking activity may contribute to the
      neuroprotective and anticonvulsant effects of vinpocetine.

PMID- 7737340
TI  - Interactions of erythro-ifenprodil, threo-ifenprodil, erythro-iodoifenprodil, and
      eliprodil with subtypes of sigma receptors.
AB  - Observations of sigma (sigma) receptor heterogeneity have prompted interest in
      identifying ligands for sigma receptor subtypes. Selective ligands for the sigma
      2 are unavailable, but [3H]ifenprodil labels sigma-2 sites. Therefore, isomers
      and analogues of ifenprodil were compared as potential sigma-2 ligands. Threo
      ifenprodil and erythro-ifenprodil had high affinity (Ki congruent to 2 nM) for
      sigma-2 sites; erythro-iodoifenprodil had moderate affinity (Ki congruent to 46
      nM); eliprodil had lowest affinity (Ki congruent to 630 nM). Threo-ifenprodil,
      which has less affinity for alpha 1-adrenoceptors than erythro-ifenprodil, was
      slightly more selective than erythro-ifenprodil for sigma-2 sites. These results
      identify threo-ifenprodil as potentially useful for studies of sigma-2 receptors.

PMID- 7737341
TI  - Reactions of the mandible to experimentally induced asymmetrical growth of the
      maxilla in the rat.
AB  - The purpose of this investigation was to examine the interrelation in growth and
      morphogenesis between the maxilla and the mandible. Asymmetrical growth was
      induced in the maxilla of 10-day-old LE/T rats by means of unilateral artificial
      synostosis of the frontonasal and frontopremaxillary sutures. Untreated rats were
      used as controls. Biometric and microscopic observations were made at the ages of
      30, 50, and 100 days. The arrest of sutural growth was followed by reduced
      sagittal growth of the maxilla, significantly more so on the treated side. Its
      anterior part became bent towards the treated side and rotated around the
      sagittal axis. In response to the primary alteration in maxillary shape, the
      mandible adapted by developing a secondary asymmetry in that it was shorter on
      the treated side than on the contralateral side throughout the experiment and
      shorter on the untreated side than in the untreated controls at 30 days. When the
      distances were adjusted for body weight, the mandibular length on the untreated
      side appeared to be virtually unaffected by the experimental procedure or even
      exceeded the control value at 50 days. The mandibular ramus was higher on the
      treated side than on the contralateral side at 30 days, and became bilaterally
      higher than in the untreated controls with increasing age. The results imply that
      the growth in length of the mandible follows that of the maxilla to some extent
      and are indicative of a restraining effect of the shortened maxilla on mandibular
      growth. The existence of a mechanism responsible for keeping the height of the
      ramus the same on both sides is suggested.

PMID- 7737342
TI  - Morphological characteristics of dentitions developing excessive root resorption
      during orthodontic treatment.
AB  - The present study focuses on orthodontically provoked, excessive root resorption.
      The purpose was to identify in these cases common morphological features in
      radiographic diagnostic material taken before treatment. The material was
      submitted by 35 Danish orthodontists. The goal was to improve the future
      orthodontic diagnostics of the dentition in order to prevent severe root
      resorption during treatment. The study indicates that: (1) there is a strong
      connection between various dental morphological characteristics, such as
      invagination, length of root, and root shapes, especially taurodontism, and the
      tendency to root resorption during orthodontic treatment; (2) there is a
      connection between anomalies in the dentition, particularly ectopia and agenesis,
      and the tendency to root resorption during orthodontic treatment; (3) there seems
      to be a connection between the pattern of resorption in the primary dentition and
      the tendency to root resorption in the permanent dentition following orthodontic
      treatment; (4) girls are more susceptible to root resorption during orthodontic
      treatment than boys; (5) one ought to be on the lookout for connections between
      condylar changes, root resorptions, and anterior open bites in connection with
      orthodontic treatment. The observation regarding root resorption in dentitions in
      which invaginations and taurodontic root shapes occur has not previously been
      reported. Also, the findings of deviant resorption patterns in both the primary
      and permanent dentitions in a considerable number of patients are new
      observations, which ought to be incorporated into orthodontic treatment planning.

PMID- 7737343
TI  - Intramatrix rotation--the frontal bone.
AB  - Intramatrix rotation during growth and development was studied by 2-D
      cephalometric technique with the use of metallic implants in the frontal bone in
      five patients at the Centre for Craniofacial Anomalies, Malmo General Hospital.
      The analysis of the frontal bone in the five patients showed rotations of the
      corpus inside the periosteal matrix from 1 to 9.5 degrees in the mid-sagittal
      plane. The essential conclusion of these observations is that an intramatrix
      rotation takes place during the development of the frontal bone. This observation
      will stimulate further studies of its nature, amount, and direction.

PMID- 7737344
TI  - Cephalometric predictors for orthopaedic mandibular advancement in obstructive
      sleep apnoea.
AB  - The cephalometric analysis of two groups: 30 sleep apnoea patients, and 30 age-
      and sex-matched control patients, established predictors for the orthopaedic
      mandibular advancement by means of the Esmarch device (ED) in treating
      obstructive sleep apnoea (OSA). Polysomnographic sleep and ventilation data
      gathered for each patient with and without mandibular advancement by means of the
      ED were compared. Cephalometric data and treatment efficacy for each patient were
      submitted to a regression analysis. Maximal efficacy is predicted by: 1. The
      combination of an orthognathic to prognathic maxilla (SNA larger than or equal to
      83 degrees) with an orthognatic to retrognathic mandible (SNB less than or equal
      to 77 degrees) 2. An anterior superior displacement of the mandible, with the
      supramentale situated at a distance from the anterior part of second cervical
      vertebra (B-HWK 2 longer than or equal to 95.5 mm) and a narrow angle between the
      skull and the mandibular ramus (SN/B-Go equal to or less than 1.5 degrees) 3.
      Short oral height (TB-PNS equal to or less than 35.5 mm), with the uvula not
      extending beyond the tongue base (UT-PNS, equal to or less than 30 mm). 4. A
      narrow oropharynx (PAS equal to or less than 3.4 mm). The narrower the SNB-angle,
      the wider the SNA-angle, and the shorter the uvula, the more effective the
      device.

PMID- 7737345
TI  - Obstructive sleep apnoea: a cephalometric study. Part I. Cervico-craniofacial
      skeletal morphology.
AB  - A comprehensive cephalometric analysis of cervico-craniofacial skeletal
      morphology in 100 male patients with obstructive sleep apnoea (OSA) and 36 male
      controls was performed. The significant aberrations in the OSA group feature: (1)
      shorter dimension of cranial base with slight counter-clockwise rotation and
      depression of clivus; (2) shorter maxillary length with normal height; (3)
      maxillo-mandibular retrognathia related to nasion perpendicular plane (N
      perpendicular FH) despite normal angles of prognathism; (4) 47 per cent of the
      OSA group had mandibular retrognathia; (5) increased anterior lower facial height
      and mandibular plane angle; (6) reduced size of bony pharynx; (7) inferiorly
      positioned hyoid bone at C4-C6 level; (8) deviated head posture with larger
      cranio-cervical angle. Cephalometric analysis is highly recommended in OSA
      patients as one of the most important tools in diagnosis and treatment planning.

PMID- 7737346
TI  - Obstructive sleep apnoea: a cephalometric study. Part II. Uvulo-glossopharyngeal
      morphology.
AB  - A comprehensive cephalometric analysis of uvulo-glossopharyngeal morphology in
      100 patients with obstructive sleep apnoea (OSA) and 36 controls was performed.
      The aberrations in OSA patients included: 1. Increased length, thickness, and
      sagittal area of soft palate (PM-U; SPT; SPA: P < 0.001) with a more upright
      position (NL/PM-U: P < 0.05) and 15 per cent more pharyngeal area occupation
      [SPA/(OPA-OA): P < 0.001]. 2. The contact length between the soft palate and the
      tongue was increased approximately two-fold (CL: P < 0.001). 3. The sagittal area
      of the tongue was 10 per cent larger (TA: P < 0.001) despite similar length and
      height and 3 per cent more oral area occupation (TA/OA: P < 0.05). 4. More
      upright tongue position (VT/FH: P < 0.05) and caudally extended tongue mass (V
      perpendicular FH: P < 0.05). 5. Decreased sagittal dimensions of nasopharynx (pm
      UPW: P < 0.001), velopharynx (U-MPW: P < 0.001) and minimum distance between the
      base of the tongue and the posterior pharyngeal wall (PASmin: P < 0.001). 6. The
      residual oropharyngeal area (area not occupied by soft tissues) was 9 per cent
      less due to larger tongue and soft palate [(TA+SPA)/OPA: P < 0.001].
      Cephalometric analysis is highly recommended in OSA patients as one of the most
      important tools in diagnosis and treatment planning.

PMID- 7737347
TI  - Radiographic characteristics in mandibular condyles of orthodontic patients
      before treatment.
AB  - Pretreatment panoramic radiographs and patient files of 625 orthodontic patients
      (269 males and 356 females), aged 4-15.9 years (mean 11.0, SD 1.7) were evaluated
      with special emphasis on the mandibular condyles and malocclusions. Radiographic
      characteristics in the mandibular condyle were seen in 14 children (2.2 per
      cent), comprising six boys (2.2 per cent) and eight girls (2.3 per cent). There
      were no statistically significant differences between orthodontic patients before
      treatment and normal population controls (n = 410,229 males and 181 females, mean
      age 11.4 years, SD 1.8). No statistically significant difference in the frequency
      of condylar characteristics was found between younger (under 12) and older (over
      12) children. Angle Class II molar relationship was the only type of
      morphological malocclusion associated (P < 0.05) with condylar characteristics.
      The means of several cephalometric measurements in the children with condylar
      characteristics were close to those of children with harmonious skeletal
      relationships.

PMID- 7737348
TI  - Orthodontic screening and third party financing.

PMID- 7737349
TI  - Fronto-sternal traction: an adjunct to orthognathic surgery.
AB  - A case is reported in which an unexpected occlusal result arose following
      bimaxillary osteotomy for correction of a skeletal Class III discrepancy. In
      order to correct the occlusion, the mandible was protracted independently of the
      recently plated maxilla, by means of a fronto-sternal traction device.

PMID- 7737351
TI  - The zeta isoform of protein kinase C controls interleukin-2-mediated
      proliferation in a murine T cell line: evidence for an additional role of protein
      kinase C epsilon and beta.
AB  - In order to address a role of protein kinase C in signal transduction through
      interleukin-2, interleukin-4, and interleukin-9 receptors, we took advantage of
      the availability of a selective protein kinase C inhibitor, GF109203X, and the
      availability of TS1 beta and TS1 alpha beta cell lines which can be maintained in
      interleukin-2, interleukin-4, or interleukin-9 independently. In this report we
      report that inhibition of protein kinase C activity by GF109203X does not block
      interleukin-4- or interleukin-9-dependent proliferation and, on the contrary,
      does block interleukin-2-dependent proliferation, suggesting that interleukin-4
      and interleukin-9 do not use signal transduction pathways mediated by protein
      kinase C and that the common gamma chain of interleukin-2, interleukin-4, and
      interleukin-9 receptors is not responsible per se for the activation of protein
      kinase C through interleukin-2 receptor. Moreover, GF109203X induces apoptosis in
      cells cultured in interleukin-2 but not in interleukin-4 or interleukin-9. Using
      antisense oligonucleotides, we report that the zeta and epsilon protein kinase C
      isoforms are involved in signaling through high-affinity interleukin-2 receptor
      and beta and zeta are involved in signaling through intermediate-affinity
      interleukin-2 receptor. Taken together, our data indicate that activation of the
      zeta, beta, and epsilon protein kinase C isoforms is an important step in
      interleukin-2-mediated proliferation.

PMID- 7737350
TI  - Thyroid hormone enhancement of estradiol stimulation of breast carcinoma
      proliferation.
AB  - Thyroid hormone (T3) and estradiol (Est) modulate biological processes by binding
      to nuclear receptor proteins that, through interactions with specific response
      elements in the regulatory regions of genes, modulate gene transcription. Est
      stimulation of estrogen receptor (ER)-positive breast carcinoma cell growth
      occurs through its ability to bind to the ER and activate gene transcription. We
      now report that physiological concentrations of T3 significantly enhance Est
      stimulation of growth of a number of human breast carcinoma cell lines. The
      effect of T3 is specific for Est stimulation of growth and has no effect on
      insulin-like growth factor-I stimulation of growth. The effect of T3 on enhancing
      Est-mediated growth was specifically blocked by the addition of ligands inducing
      retinoid X receptor (RXR) homodimer receptor formation, suggesting that RXR
      thyroid nuclear receptor (TR) heterodimer formation is required for the T3
      mediated effect on estradiol-stimulated growth. Four thyroid nuclear receptors
      have been described in tissues, TR alpha 1, alpha 2, beta 1, and beta 2. Breast
      carcinoma cells were found to express TR beta 1 and TR alpha 2 mRNA and very low
      levels of TR alpha 1 mRNA. T3 did not increase ER mRNA or protein levels and did
      not enhance Est-mediated increases in gene transcription of a number of genes,
      i.e., transforming growth factor-alpha and pS2 which contain estrogen-response
      elements (EREs) in their regulatory regions. However, T3 enhanced Est-stimulated
      ERE-TK-CAT activity. Thus significant cross-talk appears to occur between the TRs
      and ER and T3 appears to enhance Est-mediated gene transcription.

PMID- 7737352
TI  - Tetrahymena intramitochondrial filamentous inclusions contain 14-nm filament
      protein/citrate synthase.
AB  - Tetrahymena 14-nm filament protein has been shown to have dual functions as a
      citrate synthase in mitochondria and as a cytoskeletal protein in oral
      morphogenesis and pronuclear behavior during conjugation. Immunofluorescence
      studies of the 14-nm filament protein/citrate synthase in mitochondria found that
      intense mitochondrial fluorescence remained unchanged in Tetrahymena cells taken
      from logarithmic growth phase to stationary phase. However, electron microscopic
      studies showed that electron-dense rod-shaped structures found in mitochondrial
      matrices tended to increase in Tetrahymena cells in the growth decline phase. The
      rods were composed of side-by-side straight filaments with diameters of
      approximately 14 to 16 nm. Serial sections revealed that in Tetrahymena cells in
      growth decline phase, one to four electron-dense rods existed in the matrices of
      every mitochondrion. Immunoelectron microscopy using an anti-14-nm filament
      antibody clearly showed that a filament bundle of the electron-dense rod was the
      bundle of polymerized filaments of 14-nm filament protein/citrate synthase. These
      results strongly suggest that dynamic monomer-polymer conversion of the 14-nm
      filament protein/citrate synthase in mitochondria depends upon the physiological
      conditions of Tetrahymena cells.

PMID- 7737353
TI  - Activation of DNA synthesis and expression of the JE gene by catalase in mouse
      osteoblastic cells: possible involvement of hydrogen peroxide in negative growth
      regulation.
AB  - The addition of catalase isolated from bovine liver to the culture medium of
      quiescent mouse osteoblastic MC3T3-E1 cells decreased intracellular oxidized
      state, determined using fluorescent dye and laser-scanning confocal microscopy.
      The decrease in intracellular oxidized state evoked by catalase seemed to be
      involved in the arrest of growth, since catalase increased the incorporation of
      [3H]thymidine in these quiescent cells. On gel filtration of the catalase
      preparation, catalase activity and the stimulation of DNA synthesis coincided. Of
      the early response genes, JE, which is induced by competence factors, was induced
      by catalase in this cell line, whereas c-fos, c-jun, and KC mRNA levels were not
      affected. Catalase isolated from fungi and glutathione peroxidase+glutathione
      added to the culture medium also increased the steady-state level of JE mRNA.
      These results indicate that cells in the quiescent state produce hydrogen
      peroxide endogenously and that hydrogen peroxide acts as one of the mediators
      inhibiting DNA synthesis as well as the expression of JE, a growth factor
      inducible gene.

PMID- 7737355
TI  - Effect of the kinase inhibitor 2-aminopurine on the cell cycle stage-dependent
      phosphorylation state of the retinoblastoma protein.
AB  - We investigated the effect of 2-aminopurine (2-AP) on the cell cycle stage
      dependent phosphorylation state of the retinoblastoma growth suppressor protein
      (pRB). Our results suggest that 2-AP does not affect dephosphorylation of pRB
      scheduled during metaphase/anaphase of mitosis, even though 2-AP-treated cells
      never enter metaphase or anaphase. Phosphorylation of pRB, which is important for
      G1 exit, appeared to be impeded by 2-AP late during G1, coincident with a slowing
      of G1 cell progression into S phase. The significance of these data with regard
      to cell cycle regulation is discussed.

PMID- 7737354
TI  - The function of inducible promoter systems in F9 embryonal carcinoma cells.
AB  - Embryonal carcinoma (EC) cells represent an important model for studying the
      regulation of cellular differentiation during embryonic development and tumor
      formation. The differentiation of EC cells is associated with changes in the
      expression of a number of cellular genes, some of which have been implicated
      directly in the regulation of differentiation. To facilitate further studies of
      the possible roles of cellular gene products during the differentiation of EC
      cells, we have used transient transfection assays to compare the function of
      three promoter systems that direct the conditional expression of recombinant gene
      constructs. One system employs the mouse mammary tumor virus (MMTV) promoter,
      which is induced by glucocorticoid hormones. The other two systems are based on
      chimeric transactivator proteins consisting of the bacterial lac repressor or tet
      repressor, respectively, fused with a viral transactivation domain. The chimeric
      proteins function in mammalian cells as sequence-specific activators of
      transcription that are regulated by either lactose analogs or tetracycline.
      Transient transfections of mouse F9 EC cells and their differentiated cells with
      an MMTV promoter-reporter gene construct and a second plasmid encoding the rat
      glucocorticoid receptor resulted in a dramatic induction of reporter gene
      expression by glucocorticoid hormone of approximately 200-fold. The conditional
      expression system based on the tetracycline-responsive transactivator exhibited a
      similar range of reporter gene expression in response to tetracycline. In
      contrast, the system based on the lac repressor exhibited a much more limited
      range of conditional reporter gene expression in our studies. These findings and
      others discussed in this report suggest that the tetracycline-responsive promoter
      system may be useful for the conditional expression of recombinant gene
      constructs in F9 EC cells. Furthermore, data are presented indicating that the
      human beta-actin promoter should be suitable for stable expression of conditional
      transactivators, such as the tetracycline-responsive transactivator, in F9 cells
      before and after differentiation.

PMID- 7737356
TI  - A nuclear dot-like structure that has a relationship with perinuclear
      intermediate filaments.
AB  - A new type of nuclear dot-like structure was found that seems to associate with
      perinuclear intermediate filaments (IFs). A monoclonal antibody AP435 MAb (IgM),
      reactive with desmin and vimentin, recognized from several to dozens of small
      nuclear dots (AP435 dots) as well as cytoplasmic IFs in various mammalian cells
      under immunofluorescence microscopy. AP435 dots were sensitive to treatment with
      0.5% Triton X-100 while IFs were resistant. The dots disappeared during mitosis
      in some cells. They colocalized with neither centromeres nor structures involved
      in RNA processing. Many AP435 dots seem to associate with perinuclear IFs, though
      they were observed even in cells with no IFs. In cells possessing IFs AP435 dots
      separated from the bulk of the IFs and remained in the nuclear region both after
      treatment with colchicin and after treatment with cytochalasin B followed by
      centrifugation. Confocal laser-scanning fluorescence microscopy revealed the dots
      to be inside the nucleus. AP435 dots are small intranuclear structures that seem
      to interact directly or indirectly with perinuclear IFs.

PMID- 7737358
TI  - The protein complexity of the cytoskeleton of bovine and human sperm heads: the
      identification and characterization of cylicin II.
AB  - The cytoskeletal calyx of mammalian sperm heads surrounding the basolateral part
      of the nucleus contains two kinds of basic proteins: Calicin, a polypeptide of
      approximate M(r) 60,000 as estimated from SDS-PAGE, and the group of the very
      basic cylicins (pI > 10.0), formerly designated as "multiple-band polypeptides."
      Recently, bovine cylicin I has been cDNA cloned and identified as a new type of a
      cytoskeletal protein, which contains numerous Lys-Lys-Asp tripeptides accumulated
      in nine central repetitive units predicted to form alpha-helices. We now report
      the cDNA cloning and localization of a second species of cylicin, bovine cylicin
      II, present in bovine and human sperm heads: Cylicin II (488 amino acids, M(r)
      53,561, pI 10.55) shows the same prominent molecular characteristics as cylicin
      I, including a high content of charged amino acids, the abundance of Lys-Lys-Asp
      tripeptides, and repetitive units of presumably alpha-helical configuration, but
      also presents some differences. As with cylicin I mRNA, the 2.6-kb mRNA has also
      been shown to be specifically expressed in testis. The possible existence of a
      larger cylicin multigene family and its contribution to the cytoskeleton and the
      morphogenesis of the sperm head are discussed.

PMID- 7737357
TI  - Nuclear localization of the interferon-inducible protein kinase PKR in human
      cells and transfected mouse cells.
AB  - The levels and subcellular distribution of the interferon-inducible double
      stranded RNA-dependent protein kinase PKR have been measured in human Daudi cells
      and stably transfected mouse NIH 3T3 cells expressing the human protein kinase.
      Immunofluorescence of intact cells and quantitative immunoblotting of cell
      extracts indicate that PKR occurs in both the cytoplasm and the cell nucleus,
      with staining specifically in the nucleolus. The ratio of cytoplasmic to nuclear
      PKR is approximately 5:1 in control cells; in response to interferon treatment
      the protein kinase is induced severalfold in the cytoplasm whereas the level in
      the nucleus does not increase significantly. Analysis of individual transfected
      cells by confocal microscopy reveals a pattern of distribution of PKR similar to
      that in Daudi cells, with immunostaining of cytoplasm and nucleoli. Similar
      results are observed whether cells expressing wild-type PKR or a catalytically
      inactive mutant form of the kinase are analyzed, but untransfected 3T3 cells are
      not stained by the antibody used. Two-dimensional isoelectric focusing analysis
      of PKR in whole cell extracts reveals the presence of multiple forms with
      different pI values whereas similar analysis of the nuclear fraction indicates
      only one predominant species with a relatively basic pI. These results suggest
      that PKR may have a role in the cell nucleus as well as the cytoplasm and that
      the subcellular distribution of the protein kinase may be related to post
      translational modifications.

PMID- 7737359
TI  - Ionic responses to epidermal growth factor in zebrafish cells.
AB  - In mammalian cells the earliest cellular responses to epidermal growth factor
      (EGF) have been extensively characterized and include a number of ionic changes,
      such as a transient increase in calcium influx and a membrane hyperpolarization.
      The physiological significance of these ionic changes is uncertain. Therefore it
      is important to establish whether such ionic changes have been conserved during
      evolution, as this would point to an indispensable role for ionic signaling in
      growth factor action. We have isolated several embryonic zebrafish cell lines and
      studied the ionic events elicited by application of EGF to these cells. Using
      whole cell patch clamp recording, we show that activation of these receptors
      induces an outward current, which is dependent on the influx of extracellular
      calcium. The EGF-induced transmembrane currents were abolished by preincubation
      with different inhibitors of leukotriene synthesis, a feature of EGF-provoked
      ionic signaling which is also observed in mammalian cell lines. Therefore, these
      results demonstrate that ionic signaling, as well as the underlying second
      messenger systems, is not restricted to mammalian cells, indicating that ionic
      signaling is of importance in growth factor action.

PMID- 7737360
TI  - Colony-stimulating factor 1 (CSF-1) is involved in an autocrine growth control of
      rat myogenic cells.
AB  - Colony stimulating factor-1 (CSF-1) and the CSF-1 receptor (the c-fms proto
      oncogene product) are expressed during the proliferation of the L6 alpha 1 rat
      myogenic cell line and both are down-regulated during the differentiation to
      myotubes. Biologically active CSF-1 was shown to be secreted into the culture
      medium by L6 alpha 1 myoblasts and while they could not bind CSF-1, evidence was
      obtained for cell surface receptor-CSF-1 complexes. It was not possible to block
      the L6 alpha 1 proliferation by incubation with anti-CSF-1 antiserum or suramin.
      However, in L6 alpha 1 myoblasts that were stably transfected with an inducible
      anti-fms antisense construct, both c-fms protein expression and cell
      proliferation were more rapidly inhibited under induction and differentiation
      conditions than parental cells. Furthermore, under these conditions, the c-fms
      antisense transfected cells also entered myogenic differentiation more rapidly.
      These results suggest that autocrine regulation by CSF-1 that is intracellular
      may play a role in the proliferation of muscle cells and that its down-regulation
      leads to, and may be an obligatory step in, myogenesis.

PMID- 7737361
TI  - Actin polymerization localizes to the activated epidermal growth factor receptor
      in the plasma membrane, independent of the cytosolic free calcium transient.
AB  - Epidermal growth factor (EGF) induces rapid actin filament assembly in the
      membrane skeleton of A431 cells, leading to a approximately 30% rise in cellular
      filamentous actin levels. EGF-induced actin polymerization depends upon EGF
      receptor (EGFR) tyrosine kinase activity, since the selective tyrosine kinase
      inhibitor AG213 abolishes EGF-induced actin polymerization. In accordance,
      confocal laser scanning microscopy shows that newly assembled actin filaments
      localize selectively to the tyrosine-phosphorylated EGFR in the plasma membrane,
      since actin polymerization is not observed at the internalized tyrosine
      phosphorylated EGFR. Actin binding proteins (ABP's) are generally believed to
      regulate actin filament assembly. Ca2+ is known as one of the important
      regulatory factors for the activity of ABP's in vitro [15]. Therefore, we
      investigated the importance of the EGF-induced transient rise in [Ca2+]i for the
      regulation of actin polymerization in vivo. Continuous high [Ca2+]i in the
      millimolar range induces a prominent rise in cellular filamentous actin levels to
      approximately 50% over control cells. However, actin polymerization is unimpaired
      under conditions which effectively block the EGF-induced [Ca2+]i transient. These
      data demonstrate that EGF-induced actin polymerization localizes to the activated
      EGFR in the membrane skeleton, independent of the cytosolic free calcium
      transient.

PMID- 7737362
TI  - Effect of arachidonic acid on Na+/H+ exchange and neutral amino acid transport in
      sea urchin eggs.
AB  - We have investigated the role of arachidonic acid (AA) in regulation of sea
      urchin egg metabolism activated after fertilization. We show in this paper that
      addition of exogenous AA to fertilized eggs triggered a transitory stimulation of
      three ionic events related to the Na+/H+ exchange, H+ excretion, and increase in
      Nai and in pHi. AA also induced a complete inhibition of neutral amino acid
      uptake. We found that alterations in this Na(+)-dependent amino acid uptake
      induced by AA came from modifications in the intracellular sodium concentration.
      We discuss how AA or derivates may play a role in regulating intracellular free
      calcium concentration and pH.

PMID- 7737363
TI  - Selective expression of fos- and jun-related genes during osteoblast
      proliferation and differentiation.
AB  - Developmental studies of oncogene expression and transgenic animal studies
      implicate c-fos and other fos and jun family members in the regulation of bone
      tissue formation. Therefore, to initiate experimental examination of the
      hypothesis that expression of fos- and jun-related genes is functionally coupled
      to modulation of gene expression which supports bone development, we determined
      levels of expression of the principle fos and jun family members during
      progressive differentiation of normal rat calvaria-derived osteoblasts within two
      contexts. First, cellular mRNA levels were quantitated under conditions where
      expression of serum-induced early response genes had returned to basal levels.
      Our findings demonstrate high levels of c-fos, c-jun, and jun B mRNA transcripts
      during the proliferative period of osteoblast development, while expression of
      fra-1 and fra-2 is enhanced during the differentiation period. jun D is
      constitutively expressed during the time course exhibiting only a 30% decline in
      levels postproliferatively, and fos B mRNA is undetectable by Northern blot
      analyses. Late in the developmental sequence, apoptosis is evident. At this time,
      fra-1 expression is completely downregulated, while c-fos, fra-2, c-jun, jun B,
      and jun D show a dramatic enhancement in expression. Second, we addressed
      differential expression of fos and jun family members in relation to serum
      responsiveness as a function of stages of phenotypic development. Proliferating
      cells exhibit a prolonged induction of fos and jun family members in response to
      serum. While in differentiated cells, which are refractory to growth stimulus
      even when exposed to fresh serum every 2 days, a spike in fos and jun expression
      is observed. Thus, our data demonstrate significant differences in basal and
      serum responsiveness of fos and jun family members over the course of osteoblast
      differentiation. These findings are consistent with multiple lines of evidence
      linking activity of these early response genes to regulation of cell growth and
      development of the bone tissue phenotype.

PMID- 7737364
TI  - Transcriptional modulation of the human intercellular adhesion molecule gene I
      (ICAM-1) by retinoic acid in melanoma cells.
AB  - Retinoids play an important role as differentiating agents in a variety of normal
      and neoplastic cells and have been reported to induce ICAM-1 levels in melanomas,
      a phenomenon that we confirm in this paper. The effects of retinoids on gene
      expression usually involve the binding of specific retinoic acid receptor trans
      acting factors (RARs) with their ligands, which then interact with specific
      target sites, the retinoic acid responsive elements (RAREs) present in the
      promoters of responsive genes. In the case of ICAM-1, we have cloned and analyzed
      the proximal regulatory region of the human gene. We show that the ICAM-1
      promoter is RA-inducible, that it contains a putative consensus RARE
      (GGGTCATCGCCCTGCC), which binds in vitro RAR alpha complemented with RXRs, and
      that mutation of the RARE abrogates promoter responsiveness to RA. These studies
      allow ICAM-1 to be added to the list of genes transcriptionally activated by RA
      acting through an RARE element.

PMID- 7737365
TI  - The leukocyte integrin Mac-1 (CD11b/CD18) contributes to binding of human
      granulocytes to collagen.
AB  - Adhesion of polymorphonuclear granulocytes (PMN) to extracellular matrix proteins
      has been shown to be important for their migration in vitro and is thought to
      participate in PMN recruitment to sites of inflammation. Isolated human PMN
      stimulated with PMA were found to adhere best to microtiter wells coated with the
      novel ECM glycoprotein undulin (27 +/- 3% of PMNs added), followed by fibrinogen
      (25 +/- 2%), collagen type VI (18 +/- 2%), fibronectin (16 +/- 2%), and laminin
      (15 +/- 3%). PMN adhesion to other collagens ranged between 3 and 11%. Monoclonal
      antibodies recognizing CD18 and CD11b subunits of Mac-1 inhibited adhesion of PMN
      to collagens by an order of magnitude more effectively than to all noncollagenous
      substrates. F(ab')2 fragments of the anti-CD18 antibody were also able to block
      adhesion to collagens. Anti-LFA-1 (CD11a) and anti-CD44 antibodies did not
      significantly reduce adhesion. PMN adhesion was also inhibited by soluble
      collagens type II and VI (ID50 approximately 75 micrograms/ml). Binding of
      soluble radiolabeled collagens type II and VI to PMNs was specific and saturable
      with apparent dissociation constants of 2.2 and 1.9 nM, respectively, and
      specific binding of collagens type II and VI was almost completely inhibited by
      anti-CD18, but not by control antibodies. These data indicate that Mac-1 function
      is required for binding of human PMN to collagens.

PMID- 7737366
TI  - Involvement of p53 expression in cAMP-mediated apoptosis in immortalized
      granulosa cells.
AB  - In the accompanying paper we described the induction of apoptosis by extended
      cyclic AMP (cAMP)-mediated signals in primary granulosa cells and the reduction
      in this process in transformed cells expressing SV40 T antigen. In the present
      work, we examined the effect of overexpression of either wild-type or mutant p53
      on cAMP-mediated apoptosis in steroidogenic granulosa cell lines transfected with
      SV40 DNA together with the Ha-ras oncogene and a temperature-sensitive variant of
      p53, p53val135. In cell lines expressing low amounts of T antigen and high
      amounts of p53val135, growth arrest was induced by transferring the cells from
      37.5 degrees to 32 degrees C, a temperature which allows the manifestation of the
      wild-type phenotype of p53 and the induction of the WAF1 gene. While
      nonstimulated cells showed only a very modest apoptotic process, rapid and
      massive apoptosis was evident in cells stimulated by forskolin at 32 degrees C.
      The presence of serum could delay, but not abolish, this phenomenon. Progesterone
      production in such cells treated with cAMP was significantly higher at 32 degrees
      C than at 37.5 degrees C, suggesting that wild-type p53 can also enhance
      granulosa cell differentiation. Furthermore, at least at early stages, apoptosis
      is correlated with increased cell differentiation. On the other hand, in lines
      expressing high amounts of T antigen and low amounts of p53, neither an increase
      in cAMP-induced differentiation nor massive apoptosis was seen at 32 degrees C.
      These findings demonstrate that wild-type p53 can cooperate with cAMP-generated
      signals in the induction of steroidogenesis and of programmed cell death in
      granulosa cells.

PMID- 7737367
TI  - Cellular aging and transformation suppression: a role for retinoic acid receptor
      beta 2.
AB  - Cellular senescence is characterized by a finite proliferative capacity in vitro.
      Moreover, the proliferative capacity of dermal fibroblasts harvested from humans
      is inversely proportional to the age of the donor, suggesting that senescence in
      culture is a manifestation, at the cellular level, of processes that occur during
      in vivo human aging. As cellular senescence is a program that ultimately
      decreases cell proliferation, it has been hypothesized that the genetic
      mechanisms responsible for the negative growth regulation of senescence may also
      be involved in the suppression of neoplastic transformation. Retinoic acid (RA)
      and its derivatives are effective negative growth regulators and are known to
      inhibit tumor growth, in vitro and in vivo. As a first step in examining a role
      for retinoic acid in the regulation of cellular aging in human fibroblasts, we
      examined the expression of the nuclear receptors for RA (RAR alpha, RAR beta, and
      RAR gamma) in human donors of different ages. These studies demonstrate a
      selective up-regulation of RAR beta, in response to RA, in fibroblasts that
      manifest a decreased proliferative capacity. We extend these observations to show
      that this finding is independent of the age of the donor and correlates with the
      proliferative capacity of the culture as a whole. Nuclear run-on studies show
      that the increase in RAR beta mRNA accumulation is mediated by a striking
      increase in the transcription of the RAR beta 2 isoform. Senescent fibroblasts
      manifesting the transcriptional increase of the RAR beta 2 isoform also
      demonstrate transcriptional repression of the protooncogene, c-fos. Functional
      studies demonstrate that RAR beta 2, like the tumor suppressor gene p53, can
      inhibit oncogene-induced focus formation. These data provide further support for
      the contention that genetic events important in cellular senescence may also play
      a significant role in tumor suppression in humans. Moreover, these observations
      suggest that RA, through transcriptional regulation of RAR beta 2, may mediate
      aspects of the negative growth control that characterizes both states.

PMID- 7737368
TI  - The expression of heat shock protein 70 decreases with age in lymphocytes from
      rats and rhesus monkeys.
AB  - The ability of cells to express heat shock proteins in response to a stress such
      as heat is universal to all organisms and is believed to play a critical
      protective role. Therefore, it was of interest to determine the influence of
      aging on the ability of lymphocytes to express the heat shock protein hsp70 in
      response to a heat shock (42.5 degrees C for 1 h). Splenic lymphocytes isolated
      from old (24-26 months) rats showed a marked decrease in the induction of hsp70
      protein levels or hsp70 synthesis when compared to lymphocytes isolated from
      young (4-5 months) rats. An age-related decrease in the induction of hsp70 levels
      by heat also was observed in peripheral lymphocytes isolated from rhesus monkeys.
      The decline with age in the induction of hsp70 by lymphocytes from rats was
      paralleled by a decrease in the induction of hsp70 mRNA and the nuclear
      transcription of hsp70. In addition, it was found that the ability of extracts
      from heat-shocked lymphocytes to bind the heat shock element (HSE) decreased
      approximately 50% with age. Therefore, it appears that the reduced ability of
      lymphocytes from old rats to express hsp70 in response to a heat shock occurs at
      the level of transcription because of an alteration in the ability of the heat
      shock transcription factor to bind the HSE on the promoter of the hsp70 gene. The
      age-related decrease in the induction of hsp70 appears to be physiologically
      important because the viability of spleen lymphocytes exposed to high
      temperatures decreases significantly with age.

PMID- 7737369
TI  - T cell--vascular smooth muscle cell interactions: antigen-specific activation and
      cell cycle blockade of T helper clones by cloned vascular smooth muscle cells.
AB  - Histological observations have demonstrated the presence of T lymphocytes in
      atherosclerotic plaques, often in close association with vascular smooth muscle
      cells (VSMC). We have examined the interaction occurring between cloned murine
      VSMC and histocompatibility-matched, antigen-specific Th1 and Th2 cell lines.
      Incubation of either Th1 or Th2 cells with antigen-pulsed VSMC resulted in the
      formation of T cell-VSMC conjugates accompanied by morphological changes in both
      cell types. This interaction resulted in an antigen-dependent activation of IL-2
      receptor expression by the Th cells, demonstrating the ability of cloned VSMC to
      process and present antigen through the exogenous pathway. However, although the
      T cells were activated to express IL-2 receptors by antigen-pulsed VSMC, they
      were unable to progress through cell cycle. The secretion of an inhibitory
      mediator by VSMC was suggested by the observations that (1) fixation of the
      VSMC's eliminated the inhibitory signal and (2) the supernatants of IFN gamma
      primed VSMC displayed similar inhibitory activity. The inhibitory effect could
      not be abrogated with indomethacin or an inhibitor of the generation of reactive
      nitrogen intermediates, indicating that prostaglandin synthesis and/or nitric
      oxide production are not solely responsible for the inhibition of proliferation.
      Flow cytometric cell cycle analysis revealed that VSMC delivered signals
      resulting in a late G1 blockade of T cell cycle progression. Mitogen responses of
      purified primary T cells are also dramatically inhibited by IFN gamma-treated
      VSMC, despite significant IL-2 production. Our data depict a complex and intimate
      T cell-VSMC interaction and suggest that mutual activation events may occur.

PMID- 7737370
TI  - Changes in elastin-binding proteins during the phenotypic transition of rabbit
      arterial smooth muscle cells in primary culture.
AB  - Elastin, a major constituent of the media, may play an important role in the
      attachment, migration, and phenotypic properties of vascular smooth muscle cells
      (SMC). We examined binding proteins and binding sites on elastin in rabbit
      arterial SMC in primary culture. Freshly isolated cells on alpha-elastin
      underwent phenotypic transition from a contractile to a synthetic state after 5
      days of culture under serum-deficient conditions (1% FBS) and began to
      proliferate after 6 days of culture (48 h later than on plastic dishes). SMC in
      the contractile state expressed two binding proteins (130 and 36 kDa), while the
      130-kDa band was undetectable in cells in the synthetic state. The adhesion of
      freshly isolated cells and cells in the synthetic state to alpha-elastin was
      significantly inhibited by a monoclonal anti-elastin receptor antibody (BCZ-67).
      The synthetic peptide VGVAPG (Val-Gly-Val-Ala-Pro-Gly), which contains the
      recognition sequence for the elastin receptor, inhibited the adhesion of freshly
      isolated cells to alpha-elastin at 0.01-1 mM, but showed no inhibitory activity
      on the adhesion of cells in the synthetic state at 0.01 mM. These findings
      suggest that alpha-elastin suppresses the phenotypic transition of rabbit
      arterial SMC by interacting with the high-molecular-size (130 kDa) binding
      protein for a cell-binding sequence VGVAPG, while cells in the synthetic state
      can recognize alpha-elastin through interactions with the low-molecular-size (36
      kDa) binding protein for the sequence VGVAPG.

PMID- 7737371
TI  - Expression and characterization of type IV collagenases in rat lung cells during
      development.
AB  - Fetal type II epithelial cells rest on a basal lamina which separate them from
      the underlying connective tissue. At late fetal gestation, this basement membrane
      is occasionally disrupted, allowing epithelial cytoplasmic extensions to reach in
      close proximity of the interstitial fibroblast. The cellular source and enzymes
      responsible for the focal degradation of the basal membrane remains to be
      defined. In the present study, we examined the developmental expression of
      basement membrane associated type IV collagen and its degrading enzymes. Both
      fetal lung epithelial cells and fibroblasts expressed 72-kDa type IV collagenase
      and type IV (alpha 1) (alpha 2) collagen genes. Fibroblasts were enriched in the
      expression of 72-kDa type IV collagenase mRNA. Zymography showed that both cell
      types actively secrete 72- and 92-kDa type IV collagenases. Conditioned medium of
      fibroblasts contained more gelatin degrading activity than that of epithelial
      cells. At the time of appearance of basement membrane discontinuities (19-21
      days, term = 22 days), 72-kDa type IV collagenase mRNA expression in fibroblasts
      increased while that of epithelial cells remained constant. Gelatinolytic
      activity of fibroblast conditioned medium also increased during this period. In
      contrast, type IV collagen gene expression decreased in both epithelial cells and
      fibroblasts. These data are compatible with a role for type IV collagenases in
      the genesis of basement membrane disruptions during late fetal lung development.

PMID- 7737372
TI  - Apoptosis induced by c-myc overexpression is dependent on growth conditions.
AB  - Recent reports have suggested a causal link between the expression of the c-myc
      gene and ensuing cell death by apoptosis, particularly in cells prevented from
      dividing or after withdrawal of growth factors. In contrast, other studies have
      suggested that cells constitutively expressing c-myc are actually more resistant
      to cell death induced by some chemotherapeutic drugs that block cell division. We
      have examined the frequency of cell death in several Chinese hamster ovary cell
      lines that contain 20 to 30 copies of the human c-myc gene and that express high
      levels of human c-myc mRNA and protein. We found that constitutive c-myc
      expression in cells incubated at low density in medium containing 0.1% serum
      correlates with increased cell death due to apoptosis, as indicated by
      oligonucleosomal DNA fragmentation and a requirement for ongoing protein
      synthesis. However, apoptosis was not enhanced in these cells when they were
      blocked in cell division in the presence of serum, nor when grown at moderate to
      high density under low-serum conditions, despite their continued accumulation of
      high levels of c-Myc protein. Our results show that overexpression of c-Myc
      protein can promote cell death under some but not all conditions that block cell
      division and further suggest that c-Myc may accelerate but does not necessarily
      initiate apoptosis.

PMID- 7737374
TI  - Diminished responsiveness of senescent normal human fibroblasts to TNF-dependent
      proliferation and interleukin production is not due to its effect on the
      receptors or on the activation of a nuclear factor NF-kappa B.
AB  - The limited life span in culture of normal human diploid fibroblasts (HDF) has
      provided a model of cellular senescence. The short-term growth of these cells in
      culture is regulated by a number of different cytokines, including tumor necrosis
      factor (TNF), interleukin-1 (IL-1), and fibroblast growth factor (FGF). However,
      the effect of senescence on the responsiveness of HDF to these cytokines is not
      known. In the present report, we examined the effects of TNF on foreskin-derived
      HDF at different passage levels. We compared the response of HDF cells at
      population doubling (PD) 23 (young) with that of cells at PD 70 (senescent).
      Young cells proliferated in response to TNF in a dose-dependent manner. Under
      these conditions TNF had no effect on senescent HDF. The decrease in TNF
      responsiveness was found to be dependent on PD. The lack of response of senescent
      HDF was not unique to TNF, since FGF and IL-1 were also ineffective. In contrast
      to senescent HDF, TNF-dependent proliferation of young HDF could be further
      potentiated by IL-1 and FGF, suggesting an independent signaling mechanism. On
      exposure to TNF, senescent HDF produced IL-6 and IL-8, but to a much lower degree
      than that produced by young HDF. The diminished responsiveness of senescent HDF
      to TNF does not appear to be due to the difference in either receptor number or
      affinity, since senescent cells had two- to threefold higher number of TNF
      receptors than young HDF but the same affinity. TNF induced the activation of a
      nuclear transcriptional factor, NF-kappa B, equally in both young and senescent
      cells, which indicates the lack of a defect in the early events of TNF signal
      transduction in senescent fibroblasts. Overall, our results indicate that there
      is an age-dependent decline in TNF-induced proliferation and in the production of
      interleukins by fibroblasts; this unresponsiveness appears not to be due to TNF
      receptors or NF-kappa B activation. These results may have importance in
      understanding the diminished immune response, inflammation, and wound healing
      associated with aging.

PMID- 7737373
TI  - Dissociation of mitogenesis and transforming activity by C-terminal truncation of
      the insulin-like growth factor-I receptor.
AB  - We have investigated the mitogenic and transforming ability of an IGF-I receptor
      with a 108-amino-acid C-terminal truncation in R- cells, which are 3T3-like cells
      derived from mouse embryos in which the IGF-I receptor genes have been disrupted
      by targeted homologous recombination. R- cells stably transfected with expression
      plasmids encoding either a wild-type or a truncated human IGF-I receptor were
      capable of growing in serum-free medium supplemented solely with IGF-I. This
      response was observed over a wide range of receptor levels. R- cells
      overexpressing the wild-type IGF-I receptor also formed colonies in soft agar,
      and colony formation was augmented by coexpression of the SV40 large T antigen.
      However, all the examined clones of R- cells expressing the truncated IGF-I
      receptor exhibited a dramatically impaired ability to grow in soft agar, even in
      the presence of the T antigen. The inability to form colonies in soft agar was
      not due to a quantitative impairment of signal transduction, because: (1) SV40
      transformed cells with a physiological level of the wild-type IGF-I receptor did
      not respond to IGF-I with cell proliferation, but grew in soft agar; (2) R- cells
      stably transfected with both a truncated receptor and T antigen, on the contrary,
      responded with mitogenesis to IGF-I but could not form colonies in soft agar; (3)
      some clones with the truncated receptor expressed levels of receptor roughly 100
      fold the level of wild-type cells; and (4) several parameters of IGF-I receptor
      signal transduction were not impaired in cells stably transfected with a
      truncated receptor. Furthermore, overexpression of an activated ras in cells with
      the truncated IGF-IR did not restore their ability to proliferate under anchorage
      independent conditions. We conclude that the 108 amino acids of the IGF-I
      receptor are not essential for a mitogenic response to IGF-I, but are required
      for transformation (as assessed by the ability to grow in soft agar), indicating
      that these two functions can be dissociated at an intramolecular level. Moreover,
      although ras (activated) certainly plays a role in transformation, the
      transforming activity of the IGF-IR also requires signaling elements that are ras
      dependent.

PMID- 7737375
TI  - Regulation of prostaglandin H synthase 1 and 2 in MyoD transfected cells.
AB  - Exponentially growing DD-1 cells (differentiation-defective cells) synthesize
      prostaglandins, while exponentially growing MyoDD-1 cells (differentiation
      competent cells; DD-1 cells transfected with the myogenic regulatory gene MyoD)
      synthesize little or no prostaglandins and have reduced levels of prostaglandin H
      synthase-1 RNA [J. R. Wolf et al., 1993, Exp. Cell Res. 207, 439]. However, MyoDD
      1 cells have the capability of synthesizing prostaglandins in response to serum
      stimulation of serum-deprived cells. The serum stimulation of prostaglandin
      biosynthesis is associated with transient increases in both prostaglandin H
      synthase-2 RNA and protein. DD-1 cells and MyoDD-1 cells are similar with respect
      to prostaglandin biosynthesis and expression of prostaglandin H synthase-2
      following serum stimulation of serum-deprived cells. In contrast, the expression
      of prostaglandin H synthase-1 is higher in DD-1 cells as compared to MyoDD-1
      cells under all culture conditions. Thus, expression of myogenic regulatory genes
      is associated with the differential regulation of prostaglandin H synthase-1 and
      prostaglandin H synthase-2.

PMID- 7737376
TI  - Role of processing and intracellular transport for optimal toxicity of Shiga
      toxin and toxin mutants.
AB  - Cleavage of Shiga toxin A-fragment at a highly trypsin-sensitive site increases
      its enzymatic activity. To investigate the role of this cleavage site in
      intoxication of cells, we studied the routing, cleavage, and toxicity of mutant
      toxin where the trypsin-sensitive site had been eliminated. Ultrastructural
      analysis of toxin tagged with horseradish peroxidase demonstrated that wild-type
      and mutant toxins were transported from endosomes to the trans-Golgi network and
      further through the Golgi cisterns to the endoplasmic reticulum. Wild-type toxin
      was much more efficient than the mutants in provoking rapid intoxication, but
      after prolonged incubation time also mutants were highly toxic. The cells were
      able to cleave both wild-type Shiga toxin and the mutants, but the cellular
      location for cleavage appears to differ. Wild-type toxin was cleaved in the
      presence of brefeldin A, which disrupts the Golgi cisterns. This indicates that
      the cleavage occurs in the endosomes or in the trans-Golgi network. In contrast,
      the mutant Shiga-His (R248H/R251H) was not cleaved in the presence of brefeldin
      A, indicating that the cleavage can occur only after the toxin has left the trans
      Golgi network. In vitro experiments showed that the cytosolic enzyme calpain is
      able to cleave Shiga-His, and results from in vivo experiments are consistent
      with the possibility that cleavage is carried out by calpain after the mutant A
      fragment has reached the cytosol.

PMID- 7737378
TI  - Parallel expression level of dystrophin and contractile performances of rat
      aortic smooth muscle.
AB  - We have recently shown that the expression of dystrophin was in line with the
      conservation of contractility in primary and subcultured vascular smooth muscle
      cells (VSMC). In this report, we provide experimental evidence that shows the
      existence of a gradient in dystrophin expression from the aortic arch to the
      region just above the diaphragm, in line with a parallel gradient of
      contractility. On the contrary, there were no differences in caldesmon and smooth
      muscle myosin expression, as previously shown for vimentin and alpha-smooth
      muscle actin [Osborn, M., Caselitz, J., and Weber, K. (1981) Differentiation 20,
      196-202]. Overall, this is the first demonstration, in a normal adult smooth
      muscle, of a differential expression of dystrophin, in line with its contractile
      performances. In addition, these results suggest that the experimental modulation
      of dystrophin expression in cultured VSMC in line with their contractility was
      the manifestation in vitro of an actual physiological property of those cells in
      vivo.

PMID- 7737377
TI  - Melanoblast/melanocyte early marker (MelEM) is a glutathione S-transferase
      subunit.
AB  - We have biochemically characterized the antigen recognized by the
      melanoblast/melanocyte early marker (MelEM) monoclonal antibody (Mab) which
      labels early melanoblasts and melanocytes in the avian embryo [1]. While among
      the neural crest derivatives MelEM Mab is strictly specific for the melanocytic
      lineage, some endodermal derivatives such as hepatocytes react with this Mab.
      Since MelEM Mab immunoprecitates a protein of the same relative mass from both
      liver extracts and melanocytes, we immunopurified MelEM protein from liver
      extract of quail embryos at 10 days of incubation. The N-terminal sequence of
      this protein being blocked, we determined three internal peptide sequences. Our
      study reveals that the MelEM protein is an Alpha class subunit of glutathione S
      transferase which is common to hepatocytes and to neural crest-derived pigment
      cells during their differentiation.

PMID- 7737379
TI  - Proteinases are involved in both DNA fragmentation and membrane damage during CTL
      mediated target cell killing.
AB  - A number of inhibitors with different specificities were used to probe the
      involvement of proteinases in the mechanism of cytotoxic T lymphocyte (CTL)
      mediated lysis. N-Acetyl-L-tyrosine ethyl ester (ATEE) and N-benzoyl-L-arginine
      ethyl ester (BAEE) are reversible substrate inhibitors of proteinases with
      trypsin-like and chymotrypsin-like specificities, respectively. BAEE did not
      prevent either the chromium release or DNA fragmentation induced in mouse tumor
      target cells by a mixed lymphocyte population. In contrast, ATEE inhibited both
      processes. The irreversible proteinase inhibitor 3,4-dichloroisocoumarin (DCI)
      also blocked both chromium release and DNA fragmentation, but at significantly
      lower concentrations than ATEE. More importantly, chromium release was more
      susceptible to inhibition by DCI than DNA fragmentation. Addition of a
      combination of the endonuclease inhibitor aurintricarboxylic acid plus DCI
      resulted in virtually complete inhibition of both DNA fragmentation and chromium
      release when the drugs were added at the beginning of the incubation period. In
      contrast addition of DCI 15 or 30 min following initiation of the lytic cycle
      abolished the affect of DCI on fragmentation, but not lysis. A model which
      suggests a dual role for the proteinases in CTL-mediated target cell death is
      presented. First, proteinases are involved in the initiation of DNA
      fragmentation. Second, they have an ongoing function in membrane damage.

PMID- 7737380
TI  - Sendai virus and herpes virus type 1 induce apoptosis in human peripheral blood
      mononuclear cells.
AB  - Recent reports suggest that several viruses, besides human immunodeficiency
      virus, induce apoptosis in infected cells. We report here that Sendai virus or
      Herpes simplex virus type 1 (HSV-1), two potent inducers of interferon-alpha,
      caused cell death in a consistent number of human peripheral blood mononuclear
      cells. A careful analysis of infected cells by different techniques, such as
      optical and electron microscopy, DNA agarose gel electrophoresis, and
      cytofluorimetric analysis of DNA content, showed that cell death was of apoptotic
      type. Sendai virus was more apoptogenic than HSV-1, and it was further studied to
      understand the mechanism(s) by which it induced apoptosis. Physical (uv and heat)
      and chemical (beta-propiolactone) inactivation reduced or abolished the
      apoptogenic power of Sendai virus. The use of a novel technique, which allows the
      study of mitochondrial membrane potential (MMP) in intact cells by flow
      cytometry, showed that a decrease of MMP is concomitant with the appearance of
      the hypodiploid peak. These results suggest that Sendai virus and HSV-1 can be
      added to the list of viruses causing apoptosis, which appears to be a general
      mechanism occurring during viral infection.

PMID- 7737381
TI  - Clonal analysis of the effect of TGF-beta on the apoptosis-inducing activity of
      normal cells.
AB  - We have recently described induction of apoptosis in transformed fibroblasts by
      transforming growth factor type beta (TGF-beta)-treated normal fibroblasts, which
      leads to the specific elimination of transformed cells. Here we investigate
      whether the ability to eliminate transformed cells is the property of a
      specialized subpopulation of normal fibroblasts or whether all cells within the
      population are able to respond to exogenous TGF-beta by induction of elimination
      of transformed cells. Clonal analysis of the eliminative capacity of normal
      fibroblasts showed that all cells are able to induce elimination after addition
      of optimal concentrations of exogenous TGF-beta. In the absence of exogenously
      added TGF-beta, a minority of clones exhibited complete eliminative activity.
      Neither the ability nor the inability to perform elimination in the absence of
      exogenous TGF-beta was a stable characteristic of the respective cell clones. The
      number of cell clones with the ability to respond to suboptimal concentrations of
      TGF-beta increased with the passage number of the normal cells, whereas the
      number of clones inducing apoptosis in the absence of exogenous TGF-beta remained
      constant.

PMID- 7737382
TI  - Oxygen-derived free radical (ODFR) action on hyaluronan (HA), on two HA ester
      derivatives, and on the metabolism of articular chondrocytes.
AB  - Oxygen-derived free radicals (ODFR) appear to be involved in the pathogenesis of
      arthritic disorders. In order to gain new insight on their role in the phenomenon
      and as a basis for a therapeutic approach, the effect of ODFR (produced by the
      xanthine oxidase-hypoxantine system) on hyaluronic acid, on two HA ester
      derivatives, and on pig articular chondrocytes was investigated. High M(r) HA
      (1.1 x 10(6)) and low M(r) HA (16 x 10(4)) were depolymerized by ODFR but the
      methyl and hydrocortisone esters of HA (HYAFF 2P50 and HYC13) turned out to be
      nearly unaffected. When articular chondrocytes were treated with ODFR, a rapid
      nucleoside triphosphate (NTP) depletion, a transient appearance of pyrophosphate
      (PPi), and an increase of phosphomonoester and diphosphodiester concentrations
      have been observed. The NTP depletion and the DPDE increase are related to the
      concentration of free radicals. Glyceraldehyde-3-phosphate accumulation during
      ODFR treatment suggests that ATP depletion can occur as a consequence of the
      blockage of glycolysis at the level of glyceraldehyde-3-P dehydrogenase. The
      hypothesis is presented that PPi can be produced from the pathway of the FAD-NAD
      (DPDE) biosynthesis and then either hydrolyzed by endogenous pyrophosphatases or
      precipitated in the form of insoluble calcium salts. Long-term treatment (16 h)
      with ODFR causes a loss of chondrocyte membrane integrity which can be revealed
      both by an increased free LDH activity and by the characteristic signal of free
      phospholipids in the 31P-NMR spectra. While high M(r) HA shows a significant
      protective activity for chondrocytes against ODFR action, low M(r) HA and ester
      derivatives do not. It is suggested that the therapeutic activity of HA ester
      derivatives can be ascribed to their in vivo hydrolysis products.

PMID- 7737383
TI  - Serum responsiveness of the rat PCNA promoter.
AB  - Expression of proliferating cell nuclear antigen (PCNA) gene is growth-regulated.
      The growth dependence of the rat PCNA gene promoter activity was investigated.
      Cultured cells were transfected with the promoter containing plasmid and
      recovered for 48 h in serum-free medium to become quiescent. Cells were then
      cultured in serum-containing medium and harvested at certain intervals after
      serum-stimulation, and the promoter-directed chloramphenicol acetyltransferase
      activities in cell extracts were measured. The promoter used in this study
      contained sequences between -693 and +125 in relation to the transcription
      initiation site. The promoter activity was found to be serum-responsive. However,
      the serum-responsiveness of the promoter became less obvious when the amount of
      the promoter increased; meanwhile, the promoter became active in the control
      unstimulated (or quiescent) cells. It was suspected that the dosage effect was
      due to the titration of the negative regulatory factor in quiescent cells. The
      titration experiment with a reporterless construct as competitor for regulatory
      factors showed that the excess of promoter molecules reduced the promoter
      activity in serum-stimulated cells, while causing a transiently increase of
      promoter activity in quiescent cells. Based on these results, it is postulated
      that the serum-responsiveness of the rat PCNA promoter is controlled by both
      negative and positive regulatory factors. Consistent with this proposition,
      promoter binding proteins of 105 and 114 kDa were identified only in serum
      stimulated and quiescent cells, respectively, in addition to several other
      promoter binding proteins (ranging from 76 to 110 kDa) which were seen in both
      serum-stimulated and quiescent cells.

PMID- 7737384
TI  - Adenovirus infection induces rearrangements in the intranuclear distribution of
      the nuclear body-associated PML protein.
AB  - We have studied at the ultrastructural level the localization of PML protein in
      response to adenovirus infection in HeLa cells. In nuclei of noninfected cells or
      at the early stage of infection, PML accumulated at the border of nuclear bodies
      as previously described [Koken et al. (1994) EMBO J. 13, 1073-1083].
      Interestingly, we demonstrate herein that PML is also a component of the
      interchromatin granule-associated zones, recently described structures containing
      U1 snRNP [Visa et al. (1993) Eur. J. Cell Biol. 60, 308-321], suggesting that PML
      protein might be involved in some steps of splicing events. However, as the
      infection progressed these two cellular PML-containing structures disappeared but
      significant amounts of PML accumulated within two virus-induced structures,
      essentially the clear amorphous inclusions, but also the protein crystals.
      Relocalization of this protein to virus-induced structures may reflect an
      inactivation of PML functions.

PMID- 7737385
TI  - Kinematic analysis of reaching in the cat.
AB  - The present study examines the kinematic features of forelimb movements made by
      cats reaching for food in horizontal target wells located at different heights
      and distances. Wrist paths consisted of two relatively straight segments joined
      at a "via-point" in front of the aperture of the food well. In the initial lift
      phase, the paw was raised to the via-point in front of the target. In the second,
      or thrust phase, the paw was directed forward into the food well. During the
      lift, the paw was moved toward the target primarily by elbow flexion, accompanied
      by a sequence of biphasic shoulder and wrist movements. Thrust was accomplished
      primarily by shoulder flexion while the wrist and the paw were maintained at near
      constant angles. The animals varied the height of the reach primarily by varying
      elbow flexion with proportional changes in elbow angular velocity and angular
      acceleration and with corresponding variations in wrist speed. Thus, cats reached
      for targets at different heights by scaling a common kinematic profile. Over a
      relatively large range of target heights, animals maintained movement duration
      constant, according to a simple "pulse-height" control strategy (isochronous
      scaling). For reaches to a given target height, animals compensated for
      variability in peak acceleration by variations in movement time. We examined the
      coordination between the shoulder and the wrist with the elbow. Early during the
      lift, peak shoulder extensor and peak elbow flexor accelerations were
      synchronized. Late during the lift phase, wrist extensor acceleration was found
      to occur during the period of elbow flexor deceleration. We hypothesize that
      these linkages could, in part, be due to passive mechanical interactions. To
      determine how the angular trajectories of the different joints were organized in
      relation to target location, we plotted joint kinematic changes directly on the
      wrist and MCP joint paths. These plots revealed that for all target heights and
      movement speeds, wrist extensor deceleration occurred at approximately the same
      spatial location with respect to the target. This analysis also demonstrated that
      the second phase of MCP flexion occurred when the paw was below the lower lip of
      the food well, while the subsequent extension occurred after the tip cleared this
      obstacle. During thrust, wrist and MCP angles were maintained, reflecting the
      need to align the paw within the food well. Our findings suggest that cats plan
      the reaching phase of prehension as a sequence of discrete movement segments,
      each serving a particular goal in the task, rather than as an single unit.

PMID- 7737386
TI  - Head movement trajectory in three-dimensional space during orienting behavior
      toward visual targets in rhesus monkeys.
AB  - Head movement trajectories in three-dimensional space were studied in two monkeys
      with their heads free during natural and spontaneous orienting behavior toward
      objects of interest displayed in a horizontal plane. The main interest of this
      study lies in understanding the process responsible for behavioral variability
      during the execution of head movements, with special reference to "units of
      movement." The head movements were recorded by an optoelectronic movement
      analyzer working with passive markers. Algorithms have been designed to
      reconstruct the three-dimensional trajectories of the center of gravity of the
      head. Simultaneously, electromyographic activity in the four pairs of
      suboccipital muscles was studied. A quantitative evaluation of the involvement of
      the head in orienting behavior toward visual targets shows that the gaze shift is
      always produced by eye movements in combination with head movements, even with
      target eccentricities of less than 10 degrees. On the basis of 80 trials
      performed by the two monkeys, head trajectories and recruitment patterns of the
      four pairs of suboccipital muscles have been analyzed. We have been able to
      identify four elementary kinematic units which can be described as a rightward or
      leftward turning associated with a contralateral or ipsilateral bending. Each of
      these four elementary units are underlain by a precise fixed recruitment pattern
      in the four pairs of suboccipital muscles. These four sets of motor strategies
      can be combined in order to offer a certain amount of plasticity from which the
      animal builds its own head trajectory.

PMID- 7737387
TI  - Increased survival of rat EGF-generated CNS precursor cells using B27
      supplemented medium.
AB  - Previous studies suggest that a population of precursor cells from the developing
      and adult mouse striatum can be expanded in culture using serum-free, N2
      supplemented medium and mitogenic factors such as epidermal growth factor (EGF).
      Here we show that EGF-responsive precursor cells from embryonic rat striatum and
      mesencephalon can also be expanded in culture, incorporate bromodeoxy uridine
      (BrDU) and develop into spheres that either adhere to the surface of the culture
      dish or float freely in the medium. Addition of B27, a medium supplement that
      increases neuronal survival in primary CNS cultures, resulted in a tenfold
      increase in the number of proliferating cells in vitro over the first week. The
      effects of B27-supplemented medium on precursor cell survival were only seen when
      primary cultures were used, such that dividing cells grown in B27 for 1 week
      could then be transferred to either B27 or N2 medium and show similar survival
      and division rates in response to EGF. After 1, 2 or 4 weeks of growth in B27
      supplemented medium, dissociated precursor cells from either striatal or
      mesencephalic cultures could be differentiated when exposed to a poly-l-lysine
      coated substrate in serum and EGF-free medium supplemented with B27. These cells
      then matured into a mixed culture containing neurons (approximately 35% of
      cells), astrocytes (approximately 44% of cells), and oligodendrocytes
      (approximately 10% of cells), based on immunocytochemical staining with
      microtuble-associated protein (MAP2), glial fibriallary acidic protein and
      galactocerebrosidase. When whole spheres of precursor cells were allowed to
      differentiate, every one examined was found to generate neurons, astrocytes and
      oligodendrocytes in similar proportions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737388
TI  - PDGF and its receptors following facial nerve axotomy in rats: expression in
      neurons and surrounding glia.
AB  - We investigated the expression of platelet-derived growth factor (PDGF) and its
      receptors in rat facial nuclei following axotomy by in situ hybridization and
      immunohistochemistry. Facial nuclei were examined on days 3, 6, 12, 19 and 26
      postoperatively (p.o.). Strong immunoreactivity for PDGF was found in facial
      neurons and surrounding astrocytes on the ipsilateral side of the brainstem
      already after 3 days p.o. and persisted at a high level until day 26 p.o. in rats
      with a facial nerve cut injury. After crushing of the facial nerve, a similar
      increase was seen in PDGF immunoreactivity which, however, decreased after day 19
      p.o., when reinnervation had occurred. Reactive gliosis appeared on the operated
      side and was confirmed by an increase in intensity of GFAP staining. The kinetics
      of PDGF A-chain mRNA expression corresponded to the PDGF immunoreactivity,
      whereas the B-chain mRNA was present only in the neurons. The PDGF alpha-receptor
      immunoreactivity as well as the mRNA were detected in scattered glial cells. The
      density of the PDGF alpha-receptor mRNA expressing glial cells was higher on the
      injured side, but the intensity of the expression per cell did not change after
      axotomy. An increase in PDGF beta-receptor immunoreactivity was seen in the
      ipsilateral facial nuclei after 3-6 days p.o., however, the increase in the mRNA
      could not be detected. The staining persisted until day 26 p.o., when transected
      facial neurons showed heavier staining than those that had been crushed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7737389
TI  - Suppression of pilocarpine-induced status epilepticus and the late development of
      epilepsy in rats.
AB  - Status epilepticus (SE) has been related to subsequent development of epilepsy.
      The present work was aimed at elucidating the relationship between the duration
      of pilocarpine- (PILO)-induced SE and the subsequent development of epilepsy in
      rats. The latency for the appearance of the first spontaneous seizure, the
      frequency of spontaneous seizures, the cell density in the hippocampal formation
      and the density of supragranular neo-Timm staining were monitored. At 30 min, 1,
      2 and 6 h after the beginning of SE, animals were treated with diazepam plus
      pentobarbital. In non-treated rats, SE remitted spontaneously. Animals exhibiting
      30 min of PILO-induced SE did not develop spontaneous seizures. Hippocampal cell
      counts and the density of neo-Timm staining in these animals were similar to
      those observed in control rats. In the other groups longer SE durations were
      related to: shorter latency for the appearance of the first spontaneous seizure,
      increased number of the spontaneous recurrent seizures, severe cell loss in the
      hippocampal formation, or increased supragranular neo-Timm staining. These data
      suggest that more than 30 min of SE is required to produce hippocampal damage
      with subsequent synaptic reorganization of the mossy fibre pathway that could
      account for SRSs observed in the PILO model of epilepsy.

PMID- 7737390
TI  - Behavioural and neurochemical effects of superior cervical ganglionectomy in rats
      with septo-hippocampal lesions.
AB  - This longitudinal study, extending over 12 months, assessed the behavioural and
      biochemical effects of hippocampal sympathetic ingrowth (HSI) into the partially
      denervated hippocampus. Male Long-Evans rats received fimbria-fornix lesions
      (FIFO) or sham operations at 90 days of age. At the same time half of the rats
      from each group sustained bilateral ablation of the superior cervical ganglia
      (SCGX). A battery of behavioural tests, measuring spontaneous alternation,
      activity in the open field and home cage, and radial-maze performance, were
      employed, starting after one very short (16 days) and one extended (216 days)
      post-operative delay. Neurochemical analyses measuring choline acetyltransferase
      (ChAT) activity, high-affinity choline (HACU) and noradrenaline uptake by
      hippocampal synaptosomes (HANU), hippocampal noradrenaline ([NA]), serotonin ([5
      HT]) and 5-hydroxyindoleacetic acid ([5-HIAA]) concentrations were carried out in
      a dorsal, a "middle" and a ventral region of the hippocampus. Lesion of the FIFO
      induced a significant and enduring deficit in radial-maze performance, in
      addition to a persistent locomotor hyperactivity. ChAT and HACU were
      significantly depleted in all three regions of the hippocampus at 12 months, and
      these deficits were negatively correlated with maze performance. SCGX in the
      presence of the FIFO lesion significantly reduced [NA] in the middle region of
      the hippocampus, as compared to SCGX rats, and contributed to a restoration of
      lesion-induced depletions in [5-HT] and [5-HIAA] in the middle and ventral
      hippocampal regions, whilst failing to elicit any behavioural changes at either
      time point. It is concluded that if lesion-induced HSI indeed occurred, as is
      suggested by neurochemical evidence, it had no effect upon the observed
      behavioural deficits elicited by transection of the FIFO in the rat.

PMID- 7737391
TI  - The functions of the medial premotor cortex. I. Simple learned movements.
AB  - We report several studies on the effects of removing the medial premotor cortex
      (supplementary motor area) in monkeys. The removal of this area alone does not
      cause either paralysis or akinesia. However, the animals were poor at performing
      a simple learned task in which they had to carry out an arbitrary action: they
      were taught to raise their arm in order to obtain food in a foodwell below. They
      were impaired whether they worked in the light or the dark. They were impaired
      when they had to perform the movements at their own pace, but much less impaired
      when a tone paced performance. Monkeys with lesions in the anterior cingulate
      cortex were as impaired as monkeys with medial premotor lesions at performing
      this task at their own pace. However, monkeys with lateral premotor lesions were
      less impaired. We conclude that the medial premotor areas play a crucial role in
      the performance of learned movements when there is no external stimulus to prompt
      performance.

PMID- 7737392
TI  - The functions of the medial premotor cortex. II. The timing and selection of
      learned movements.
AB  - Monkeys with medial premotor cortex (MPC) lesions are impaired on a simple
      learned task that requires them to raise their arm at their own pace. However,
      they can succeed on this task if they are given tones to guide performance. In
      the externally paced task the tones could aid performance in several ways. They
      tell the animal when to act (trigger), they remind the animal that food is
      available and so motivate (predictor), and they remind the animal of what to do
      (instruction). Monkeys with MPC lesions can respond quickly to visual cues
      (experiment 1), and they can respond as well as normal monkeys when there is no
      immediate trigger (experiment 2). They are also quick to relearn a task in which
      external cues tell them what to do (experiment 5). However, they are poor at
      selecting between movements on a simple motor sequence task (experiment 3), and
      they are poor at changing between two movements (experiment 4). On these tasks
      there were cues to act as triggers and predictors, but there were no external
      instructions. We conclude that the reason why animals with MPC lesions perform
      better with external cues is that these cues act as instructions. The cues prompt
      retrieval of the appropriate action. This is true whether the task requires the
      animal to perform one action (experiments 1 and 2) or to select between actions
      (experiments 3 and 4).

PMID- 7737393
TI  - Short-latency trigemino-cervical reflexes in man.
AB  - We describe a reflex evoked in neck muscles by stimulation of afferent fibres in
      the trigeminal nerve. The clearest responses were seen in averaged, unrectified,
      monopolar surface electromyographic (EMG) recordings from active
      sternocleidomastoid muscles after stimulation of the infraorbital nerve. They
      consisted of a bilateral positive/negative (p19, n31) wave with a mean onset
      latency of 12.9 ms which corresponded to a period of inhibition in the underlying
      motor unit activity. Responses also could be seen in splenius and trapezius, but
      not in arm muscles. Stimuli to other branches of the trigeminal nerve
      (supraorbital or mental) did not produce such clear effects. The threshold for
      the reflex was relatively low (2-4 times perceptual threshold) and its size
      scaled with the level of background EMG in an approximately linear fashion.
      Responses to infraorbital stimulation did not interact with other short-latency
      inhibitory responses in the sternocleidomastoid muscle evoked by loud acoustic
      clicks or stimulation of the median nerve at the wrist. We suggest that the
      infraorbital response is part of a head withdrawal reflex involving an
      oligosynaptic trigemino-cervical system similar to that described in the cat.

PMID- 7737394
TI  - Coordinated responses following mechanical perturbation of the arm during
      prehension.
AB  - We have investigated how the control of hand transport and of hand aperture are
      coordinated in prehensile movements by delivering mechanical perturbations to the
      hand transport component and looking for coordinated adjustments in hand
      aperture. An electric actuator attached to the subject's right arm randomly
      pulled the subject backwards, away from the target, or pushed them towards it,
      during a quarter of the experimental trials. A compensatory adjustment of hand
      aperture followed the immediate, mechanical effects of the perturbation of hand
      transport. The adjustment appeared to return the subject towards a stereotyped
      spatial relation between hand aperture and hand transport. These spatial patterns
      suggest how the two components may be coordinated during prehension. A simple
      model of this coordination, based on coupled position feedback systems, is
      presented.

PMID- 7737395
TI  - Perception of arm orientation in three-dimensional space.
AB  - The purpose of this investigation was to determine the preferred coordinate
      system for perception of arm (humerus) orientation in three-dimensional space.
      Perception of arm orientation relative to trunk-fixed versus earth-fixed axes
      were compared in seven human subjects. The experimenter first moved the subject's
      trunk and arm into a target configuration (in which the arm's orientation
      relative to the trunk and/or earth was perceived and memorized by the subject)
      and then moved the trunk and arm to a new configuration. The blindfolded subject
      then attempted to reproduce the target orientation of their arm relative to
      either the trunk (i.e., reproduce shoulder angles--intrinsic kinesthetic
      coordinate system) or earth-fixed axes (extrinsic kinesthetic coordinate system).
      Perceptual errors were similar for both shoulder (arm relative to trunk) and
      extrinsic (arm relative to earth) angles. However, elevation angles were
      perceived with greater accuracy than yaw angles in the two coordinate systems.
      Also, perceptual errors for arm yaw angles in the extrinsic kinesthetic
      coordinate system task were better predicted from changes in trunk orientation
      than the errors for other angles. Furthermore, four subjects matched arm yaw
      angle relative to the trunk-fixed axis more accurately than to the earth-fixed
      axis in the extrinsic coordinate system task. These results suggests a bias
      toward perception of yaw angles relative to trunk-fixed axes (i.e., in an
      intrinsic coordinate system). These data suggest that the preferred coordinate
      system for kinesthetic perception of arm orientation is probably fixed in the
      trunk.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737396
TI  - An in vitro 1H nuclear magnetic resonance study of the temporoparietal cortex of
      Alzheimer brains.
AB  - The concentrations of selected metabolites in the posterior temporoparietal
      cortex of 13 Alzheimer's diseased (AD) and four nondemented postmortem brains (of
      individuals between the ages of 63 and 95) were determined using high-resolution
      1H nuclear magnetic resonance (NMR) spectroscopy. The estimates for glutamate and
      inositol for AD brains did not show any statistically significant difference (P >
      0.05) from those for the nondemented brains. The putative neuronal marker N
      acetyl aspartate (NAA), creatine, and GABA were decreased in AD brains compared
      with the nondemented brains. The estimates for creatine, glutamate, and GABA
      showed significant linear correlations with those of NAA. Creatine, glutamate,
      GABA, and NAA appeared to be negatively correlated with the neurofibrillary
      tangles. Our results support a neuronal loss in the posterior temporoparietal
      cortices of AD brains.

PMID- 7737397
TI  - Dynamics of torsional optokinetic nystagmus under altered gravitoinertial forces.
AB  - The purpose of the present study was to investigate the influence of varying
      gravitoinertial forces on torsional optokinetic nystagmus during parabolic
      flights. Using the scleral search-coil technique, we measured the gain and phase
      lag of torsional optokinetic nystagmus (OKN) induced by a hemispherical visual
      display rotating about the roll axis either at constant velocity or sinusoidally
      at various frequencies during level flight, hypogravity, and hypergravity.
      Compared with level flight, there was a significant increase in slow-phase eye
      velocity during hypogravity and an increase in nystagmic frequency. An absence of
      well-developed torsional optokinetic afternystagmus was observed in all three
      gravity conditions. Other characteristics included a lack of a slow rise
      component. These data suggest that otolith inputs do affect torsional optokinetic
      afternystagmus suggests that the velocity storage pathways do not contribute
      significantly to the torsional OKN system in humans.

PMID- 7737398
TI  - Are non-relevant objects represented in working memory? The effect of non-target
      objects on reach and grasp kinematics.
AB  - The role of visual information and the precise nature of the representations used
      in the control of prehension movements has frequently been studied by having
      subjects reach for target objects in the absence of visual information. Such
      manipulations have often been described as preventing visual feedback; however,
      they also impose a working memory load not found in prehension movements with
      normal vision. In this study we examined the relationship between working memory
      and visuospatial attention using a prehension task. In this study six healthy,
      right-handed adult subjects reached for a wooden block under conditions of normal
      vision, or else with their eyes closed having first observed the placement of the
      target. Furthermore, the role of visuospatial attention was examined by studying
      the effect, on transport and grasp kinematics, of placing task-irrelevant
      "flanker" objects (a wooden cylinder) within the visual field on a proportion of
      trials. Our results clearly demonstrated that the position of flankers produced
      clear interference effects on both transport and grasp kinematics. Furthermore,
      interference effects were significantly greater when subjects reached to the
      remembered location of the target (i.e., with eyes closed). The finding that the
      position of flanker objects influences both transport and grasp components of the
      prehension movement is taken as support for the view that these components may
      not be independently computed and that subjects may prepare a coordinated
      movement in which both transport and grasp are specifically adapted to the task
      in hand. The finding that flanker effects occur primarily when reaching to the
      remembered location of the target object is interpreted as supporting the view
      that attentional processes do not work efficiently on working memory
      representations.

PMID- 7737399
TI  - Spatial localization: tests of a two-process model.
AB  - The present study examined the recently proposed two-process model of
      localization performance in which a shift of attention, providing coarse location
      information, is followed by a saccadic eye movement, providing fine location
      information. In experiment 1 the nature of the localization response was
      manipulated. In contrast to the indirect response mode used in the study by Adam
      et al., i.e., manipulating the "arrow" keys to move the cursor to the target
      location, experiment 1 required subjects to point to the target location. The
      high degree of similarity between the pattern of results obtained with the
      pointing and cursor response indicated that performance in the localization
      paradigm was not differentially affected by the nature of the required response.
      In experiment 2 the characteristics of the backward masking stimulus was
      manipulated by employing three masking conditions: (1) a long-duration mask; (2)
      a short-duration mask (100 ms); and (3) a no-mask condition. Results showed that
      the long-duration mask caused interference at short and facilitation at long
      intervals between onset of target and mask; the short-duration mask caused
      interference only at short intervals. Overall the findings were consistent with
      the two-process model of localization performance.

PMID- 7737400
TI  - Adaptive plasticity in the control of locomotor trajectory.
AB  - Eight human subjects were exposed to 2 h of walking on the perimeter of a
      horizontally rotating disc with the body remaining still in space. After
      adaptation to this experience subjects were blindfolded and asked to walk
      straight ahead on firm ground. When doing so all subjects generated curved
      walking trajectories of radii ranging from 65 to 200 inches and angular
      velocities from 7 to 20 deg/s. Subsequent trials over the next half hour revealed
      retained, but decreasing, trajectory curvature. Angular velocities associated
      with these trajectories were well above vestibular sensory threshold, yet all
      subjects consistently perceived themselves as walking straight ahead. The
      blindfolded subjects were also asked to propel themselves in a straight line in a
      wheel chair. Post-adaptation wheel chair trajectories showed no change from those
      before adaptation. Hence we infer that it was the relation between
      somatosensory/motor elements of gait and the perception of trunk rotation that
      had been remodelled during walking on the turning disc. This novel form of
      adaptive plasticity presumably serves to maintain optimal values of central
      neural parameters that control the trajectory of locomotion. The findings may
      have significant implications for the diagnosis and rehabilitation of locomotor
      and vestibular disorders.

PMID- 7737401
TI  - Synaptic linkages between red nucleus cells and limb muscles during a multi-joint
      motor task.
AB  - The magnocellular red nucleus (RNm) becomes highly active when a monkey reaches
      to grasp an object. However, the only spike-triggered averaging studies of the
      RNm to date have been restricted to a simple wrist tracking paradigm and
      electromyographic (EMG) measurements of muscles of the forearm. We have now
      measured EMG signals from a large number of muscles throughout the shoulder, arm,
      forearm, and hand during a variety of tasks, including unconstrained reaching and
      grasping movements. Relations between these EMG signals and single-unit activity
      were assessed by on-line spike-triggered averaging and revealed significant post
      spike effects among muscles of the shoulder and proximal arm, as well as
      intrinsic hand muscles. Although there remained a strong bias toward the extensor
      muscles of the forearm, as has been shown earlier, these results reinforce the
      importance of the RNm in the control of coordinated, whole-limb reaching
      movements.

PMID- 7737402
TI  - Magnification factors, receptive field images and point-image size in the
      superior colliculus of flying foxes: comparison with the primary visual cortex.
AB  - The magnification factor (MF) of the stratum griseum superficiale (SGS) of the
      superior colliculus (SC) was calculated based on visual receptive fields recorded
      from anaesthetised and paralysed flying foxes (Pteropus spp.). In areal terms,
      the MF at the representation of central vision was 4-6 times larger than that in
      the peripheral representation. This variation is less marked than that observed
      in the primary visual area (V1), but is roughly that expected if the retinotopic
      map in the SC was defined by the distribution of ganglion cells in the retina.
      Two measures of the functional spread of activity in the SC, the receptive field
      images and the point-image size, were calculated. Receptive field images are
      remarkably similar throughout the SC. As in V1, the point-image size in the SGS
      of flying foxes is 0.5-0.6 mm and varies little with eccentricity. Bilateral
      ablation of the visual cortex results in a reduction of the mean receptive field
      size of neurones in the SGS, and the point-image size is reduced by half.
      However, the shape of the point-image function is not affected. These results
      demonstrate that the spread of activity in the SC is nearly constant throughout
      the retinotopic map and that this is primarily a result of the direct retinal
      projection. Although the visual cortex has an expanded central representation in
      comparison with the SC, the corticotectal pathway does not exert a preferential
      influence on the central representation of the SC.

PMID- 7737403
TI  - Processed products of the hevein precursor in the latex of the rubber tree (Hevea
      brasiliensis).
AB  - The 20 kDa precursor of hevein and its C-terminal 14 kDa domain have been
      isolated. Sequence analysis of the C-terminal tryptic peptides of these proteins
      and comparison with the cDNA sequence indicate that they represent mature forms
      from which a C-terminal propeptide, possibly involved in vacuolar targeting, has
      been removed. The molar ratio of hevein to the C-terminal domain in the lutoid
      body fraction of rubber latex is about 30:1. This indicates that not only the pre
      and propeptides but also the 14 kDa domain are removed by proteolysis or other
      processes in the latex vessel after the processing of hevein has taken place.

PMID- 7737404
TI  - Thrombospondin 1 binds to the surface of bovine articular chondrocytes by a
      linear RGD-dependent mechanism.
AB  - Thrombospondin 1 is present in articular cartilage and is synthesized by
      chondrocytes. Adult bovine articular chondrocytes in serum-free medium were
      evaluated in a solid-phase assay for their ability to attach to thrombospondin 1
      isolated from human platelets. The chondrocytes attached to the thrombospondin 1
      by a mechanism that was inhibited by a synthetic linear GRGDSP but not a GRGESP
      peptide. The cells, however, did not spread on thrombospondin 1, but did spread
      on fibronectin and Pep-Tite 2000, a synthetic RGD-containing peptide.
      Preincubation of thrombospondin 1 with EDTA irreversibly inhibited its capacity
      to attach to chondrocytes. We conclude that thrombospondin 1 binds to
      chondrocytes by its RGD sequence.

PMID- 7737405
TI  - A novel Ca(2+)-dependent step in exocytosis subsequent to vesicle fusion.
AB  - Exocytosis begins with formation of a small fusion pore which then expands
      allowing rapid release of granular contents. We studied the influence of
      cytoplasmic free Ca2+ ([Ca2+]i) on the conductance of the initial pore and on the
      dynamics of subsequent expansion in horse eosinophils using the patch clamp
      technique. The mean initial conductance is approximately 200 pS independent of
      [Ca2+]i. This value is close to that previously found in beige mouse mast cells.
      The pore subsequently expands by 18 nS/s at [Ca2+]i < 10 nM, by 40 nS/s at
      [Ca2+]i = 1.5 microM and by 90 nS/s at [Ca2+]i = 10 microM. These results show
      that the structure of the initial fusion pore is independent of cytoplasmic Ca2+.
      However, the pore expansion is a Ca(2+)-dependent process modulating secretion at
      a step later than vesicle-plasma membrane fusion.

PMID- 7737406
TI  - Cytosolic calcium facilitates release of secretory products after exocytotic
      vesicle fusion.
AB  - We monitored single vesicle exocytosis by simultaneous measurements of cell
      membrane capacitance as an indicator of fusion and amperometric detection of
      serotonin release. We show here that vesicle-plasma membrane fusion in rat mast
      cell granules is followed by a variable, exponentially distributed, delay before
      bulk release. This delay reflects the time required for the expansion of the
      exocytotic fusion pore, lasting, on average, 231 ms in resting cytosolic calcium,
      [Ca2+]i (50 nM). In the presence of [Ca2+]i in the low micromollar range, the lag
      between fusion and release was reduced to 123 ms. The characteristics of the
      amperometric signals were unchanged by [Ca2+]i. These results show a novel site
      of regulation in the exocytotic process, the fusion pore, which may represent a
      different mechanism facilitating transmitter release.

PMID- 7737407
TI  - Human androgen-induced growth factor in prostate and breast cancer cells: its
      molecular cloning and growth properties.
AB  - Androgen-induced growth factor (AIGF) has hormone-regulated properties in the
      mouse Shionogi carcinoma cell line. To investigate whether or not it is involved
      in growth of human hormone-responsive cancers, we isolated the human AIGF gene
      from a placental genomic library. Genomic analyses suggested that the AIGF gene
      was about 6.5 kilobases in length containing five exons. The deduced amino acid
      sequence of human AIGF was completely identical with that of the mouse. RT-PCR
      analyses showed that prostate and breast cancer cell lines, LNCaP, PC-3, and MCF
      7, slightly expressed the AIGF gene. Recombinant AIGF enhanced the growth of the
      human prostate cancer LNCaP cells, and it also markedly stimulated the growth of
      fibroblasts. These in vitro findings suggest that AIGF might be a possible
      autocrine or paracrine factor in hormone-responsive cancers.

PMID- 7737408
TI  - Analysis of recombination junctions in extrachromosomal circular DNA obtained by
      in-gel competitive reassociation.
AB  - Essentially all eukaryotic cells contain circular extrachromosomal DNA as a
      result of excision from the chromosomes. To obtain insight into the nature of
      recombination associated with the occurrence of such DNA species and its
      biological significance, we analyzed a library enriched in recombination
      junctions which was constructed by a novel DNA subtraction technique; in-gel
      competitive reassociation (IGCR). Furthermore, we also introduced inverse PCR to
      characterize chromosomal DNA fragments containing the recombination junctions. At
      least 45% of the clones in the library constructed by the IGCR procedure
      comprised DNA with recombination junctions. Nucleotide sequence analysis of the
      recombination junctions indicated that three of four extrachromosomal DNAs thus
      analyzed were produced through recombination between sequences with a 3-5 bp
      homology in the chromosomes. One extrachromosomal DNA was apparently generated
      through non-homologous recombination, possibly by end-to-end joining. These
      results have demonstrated the usefulness of IGCR in concentrating recombination
      junctions, which provide the most direct evidence for the mechanism of the
      recombinational events involved, from highly complex genomes.

PMID- 7737409
TI  - Requirement of the two-headed structure for the phosphorylation dependent
      regulation of smooth muscle myosin.
AB  - It is known for smooth muscle myosin that while acto-HMM ATPase activity is
      regulated by phosphorylation, acto-S-1 ATPase activity is not regulated. To
      clarify the heavy chain structure required for the regulation, smooth muscle
      myosin containing 7 different lengths of the S-2 portion were expressed in Sf9
      insect cells using Baculovirus expression system. Myosin containing longer than
      991 residues of heavy chain formed a stable two-headed structure while myosin
      with shorter than 944 residues of heavy chain formed a single-headed structure,
      indicating that the residues Gln945-Asp991 are critical for the formation of the
      two-headed structure. The actin activated ATPase activity of myosin mutants
      having a two-headed structure was activated by phosphorylation while that of
      myosin mutants that failed to form the two-headed structure was completely
      independent of phosphorylation. These results suggest that the two-headed
      structure is critical for the phosphorylation-dependent regulation.

PMID- 7737410
TI  - Bicarbonate requirement for the donor side of photosystem II.
AB  - Suppression of electron flow (and its subsequent restoration with 3-10 mM NaHCO3)
      on the donor side of photosystem II is shown upon either a partial depletion of
      pea subchloroplast membranes in bicarbonate or the addition of 5-20 microM
      formate. At higher concentrations (5 mM) formate induces the known 'bicarbonate
      effect' on the acceptor side of photosystem II. In preparations depleted of
      manganese the restoration of electron flow with 0.1-0.2 microM MnCl2 (2-4 Mn per
      photosystem II reaction center) occurs only in the presence of bicarbonate and it
      is accompanied by an increased functional binding of manganese. Restoration of
      electron flow with diphenylcarbazide or NH2OH does not require the addition of
      NaHCO3. It is suggested that bicarbonate participates in the formation of the Mn
      cluster capable of water oxidation or serves as a substrate for the water
      oxidizing center.

PMID- 7737411
TI  - Cloning, functional expression and tissue distribution of human alpha 1c
      adrenoceptor splice variants.
AB  - We report the cloning and characterization of two isoforms of human alpha 1c
      adrenoceptor cDNA (alpha 1c-2, alpha 1c-3). These isoforms are generated by
      alternative splicing and differ from the clone we previously isolated (alpha 1c
      1) in their length and sequences of the C-terminal domain. Tissue distribution of
      mRNAs showed that these variants co-express with alpha 1c-1 in the human heart,
      liver, cerebellum and cerebrum. Despite the structural differences, functional
      experiments in transfected CHO cells showed that the three isoforms have similar
      ligand binding properties, and all couple with phospholipase C/Ca2+ signaling
      pathway.

PMID- 7737412
TI  - Constitutive activation of muscarinic receptors by the G-protein Gq.
AB  - In the absence of ligands, G-protein coupled receptors interconvert between
      active and inactive conformations. These conformations are stabilized by agonists
      and antagonists, respectively. Like agonists, G-proteins are thought to
      preferentially associate with receptors in the active conformation and should
      therefore be able to promote their formation in the absence of agonist. We show
      that over-expression of Gq induces constitutive activation of compatible
      muscarinic receptors and that this activity is blocked by muscarinic antagonists.
      Gq also increases the potency and efficacy of agonists. These results indicate
      that regulation of G-protein levels has a profound impact on receptor control of
      cellular physiology, even in the absence of agonist ligands.

PMID- 7737414
TI  - Computer-assistant prediction of phospholipid binding sites of caldesmon and
      calponin.
AB  - The primary structure of smooth muscle caldesmon and calponin was screened for
      the presence of amphiphilic alpha-helices which can participate in the formation
      of protein-lipid contacts. Only one caldesmon segment (residues 645-660) having a
      predominantly alpha-helical structure and high hydrophobic moment satisfies all
      criteria for a surface-seeking helix and is predicted to be involved in the
      caldesmon-phospholipid interaction. This prediction agrees with experimental
      results indicating that one of the caldesmon-phospholipid binding sites is
      located in the sequence 628-658 [Bogatcheva et al. (1994) FEBS Lett. 342, 176].
      Two segments of calponin (residues 45-55 and 85-95) exhibit high hydrophobic
      moments and the sequence 85-95 is characterized by a high probability of alpha
      helix formation. This may suggest that at least one of these segments could
      facilitate the calponin-phospholipid interaction and that calponin, as with many
      other actin binding proteins, is able to interact with membranes.

PMID- 7737415
TI  - Alterations in protein synthesis induced by C2 toxin in 3T3 cells.
AB  - We have studied the effect of actin skeleton depolymerisation induced by C2 toxin
      on protein synthesis in 3T3 cells. The toxin that was purified from culture
      medium of Clostridium botulinum type C was shown to specifically ADP-ribosylate
      actin in vitro and in vivo. Cells exposed to C2 toxin were rounded off, which was
      accompanied by disappearance of stress fibers. The rate of total protein
      synthesis decreased two-three times in the treated cells. This correlated with
      the reduction in amount of polyribosomes. The rates of specific protein synthesis
      were compared using 2D electrophoresis of pulse-labeled proteins. Dramatic
      changes were observed in the synthesis of a small group of cellular proteins. Our
      results indicate that actin filament depolymerization affects gene expression at
      the level of translation and/or through the control of mRNA concentrations.

PMID- 7737413
TI  - Essential aspartic acid residues, Asp-133, Asp-163 and Asp-164, in the
      transmembrane helices of a Na+/H+ antiporter (NhaA) from Escherichia coli.
AB  - The importance of negatively charged residues in transmembrane helices of many
      cation-coupled transporters has been widely demonstrated. Four Asp residues were
      located in the putative transmembrane helices of the Escherichia coli Na+/H+
      antiporter, NhaA. We replaced each of these Asp residues by Asn in plasmid
      encoded nhaA and expressed these constructs in an E. coli mutant defective in
      both nhA and nhaB. Substitution of Asp-65 or Asp-282 (in the extramembrane
      region) had no effect on supporting the host mutant growth in the high NaCl- or
      LiCl-containing medium, and these two mutants had normal Na+/H+ and Li+/H+
      antiporter activities. In contrast, substitution of Asp-133, Asp-163 or Asp-164
      was detrimental to survival of the host mutant and impaired both Na+/H+ and
      Li+/H+ antiporter activities. These three Asp residues, conserved in the nhaA
      homologs from different species and which are located closely in the 3rd and 4th
      putative transmembrane helices, appear to play important roles in cation binding
      and transport.

PMID- 7737416
TI  - Glucose-enriched medium enhances cell-mediated low density lipoprotein
      peroxidation.
AB  - A 1 week preculture of endothelial or smooth muscle cells in glucose-enriched
      (11.2 to 44.8 mM) media resulted in a marked enhancement of the subsequent
      ability of cells to oxidize low density lipoprotein, as assessed by the lipid
      peroxidation end product and conjugated diene content of the particle, its
      relative electrophoretic mobility and its degradation by macrophages. This
      phenomenon is correlated to a marked stimulation of superoxide anion secretion by
      cells. Such an effect of elevated glucose concentration on cell-induced LDL
      oxidative modification could be involved in the increased occurrence of
      atherosclerotic lesions in diabetes mellitus.

PMID- 7737417
TI  - Branching and elongation with lactosaminoglycan chains of N-linked
      oligosaccharides result in a shift toward termination with alpha 2-->3-linked
      rather than with alpha 2-->6-linked sialic acid residues.
AB  - The activity of bovine colostrum CMP-NeuAc:Gal beta 1-->4GlcNAc beta-R alpha 2-
      >6-sialyltransferase (alpha 6-NeuAcT) toward oligosaccharides that form part of
      complex-type, N-linked glycans appears significantly reduced when a bisecting
      GlcNAc residue or additional branches are present, or when core GlcNAc residues
      are absent. By contrast human placenta CMP-NeuAc:Gal beta 1-->4GlcNAc beta-R
      alpha 2-->3-sialyltransferase (alpha 3-NeuAcT) is much less sensitive to
      structural variations in these acceptors. Furthermore the alpha 3-NeuAcT shows a
      much higher activity than the alpha 6-NeuAcT with oligosaccharides that form part
      of linear and branched lactosaminoglycan extensions. These results indicate that,
      in tissues that express both enzymes, branching and lactosaminoglycan formation
      of N-linked glycans will cause a shift from termination with alpha 2-->6-linked
      sialic acid to termination with alpha 2-->3-linked sialic acid residues. These
      findings provide an enzymatic basis for the sialic acid linkage-type patterns
      found on the oligosaccharide chains of N-glycoproteins.

PMID- 7737418
TI  - Dexamethasone inhibits ozone-induced gene expression of macrophage inflammatory
      protein-2 in rat lung.
AB  - To address the potential role of the chemokine macrophage inflammatory protein-2
      (MIP-2) in airway inflammation, we examined whether MIP-2 may play a role in
      ozone-induced neutrophilic inflammation of airways and its modulation by
      dexamethasone in rat lung. Following ozone exposure, MIP-2 mRNA expression in the
      lung peaked at 2 h after exposure and slowly declined thereafter. Dexamethasone
      suppressed ozone-induced MIP-2 mRNA expression and neutrophil accumulation in the
      lung. We suggest that the MIP-2 mRNA induction may switch on the neutrophilic
      influx observed in this model of lung inflammation. Furthermore, the MIP-2
      expression is regulated by dexamethasone which may represent one of the
      mechanisms by which glucocorticoids exert their potent anti-inflammatory
      properties.

PMID- 7737419
TI  - Cadherin-dependent cell aggregation is affected by decapeptide derived from rat
      extracellular super-oxide dismutase.
AB  - A synthetic HAV-containing decapeptide homologous to the amino acid sequence 44R
      Q53 in rat extracellular superoxide dismutase B affects cadherin-dependent cell
      aggregation. Cell lines, some of them transfected, expressing different types of
      cadherins were tested using in vitro cell aggregation and cell dissociation
      assays. A concentration-dependent inhibition of aggregation by the EC-SOD-derived
      HAV-containing peptide was detected only in N-cadherin expressing cells. These
      results suggest the localisation and possible protective role of EC-SOD B for
      cells expressing N-cadherin.

PMID- 7737421
TI  - Isozyme hybrids within the protruding third loop domain of the barley alpha
      amylase (beta/alpha)8-barrel. Implication for BASI sensitivity and substrate
      affinity.
AB  - Barley alpha-amylase isozymes AMY1 and AMY2 contain three structural domains: a
      catalytic (beta/alpha)8-barrel (domain A) with a protruding loop (domain B;
      residues 89-152) that binds Ca2+, and a small C-terminal domain. Different parts
      of domain B secure isozyme specific properties as identified for three AMY1-AMY2
      hybrids, obtained by homeologous recombination in yeast, with crossing-over at
      residues 112, 116, and 144. The AMY1 regions Val90-Thr112 and Ala145-Leu161 thus
      confer high affinities for the substrates alpha-D-maltoheptaoside and amylose,
      respectively. Leu117-Phe144, and to a lesser degree Ala145-Leu161, are critical
      for the stability at low pH characteristic of AMY1 and for the sensitivity to
      barley alpha-amylase/subtilisin inhibitor specific to AMY2.

PMID- 7737422
TI  - The highly conserved defender against the death 1 (DAD1) gene maps to human
      chromosome 14q11-q12 and mouse chromosome 14 and has plant and nematode homologs.
AB  - We have cloned the cDNA encoding the mouse DAD1 (defender against apoptotic cell
      death) protein. While showing an expected high homology with the previously
      cloned human and Xenopus DAD1-encoding cDNAs, this sequence has striking homology
      to partial cDNA sequences reported from O. sativa (rice) and C. elegans
      (nematode), suggesting the existence of plant and invertebrate homologs of this
      highly conserved gene. The human and mouse DAD1 genes map to chromosome 14q11-q12
      and chromosome 14, respectively. This mapping data supports and extends the
      previously reported similarities between human chromosome 14q and mouse
      chromosome 14.

PMID- 7737420
TI  - Expression of protein kinase C isozymes in hippocampal neurones in culture.
AB  - Several protein kinase C (PKC) isozymes were analyzed by immunoblot and
      immunocytochemistry in cultures of hippocampal neurones at several stages of
      differentiation. Our findings reveal the existence of two distinct patterns of
      expression. Firstly, conventional PKC isozymes alpha, beta and gamma, that are
      expressed at very low levels during the initial stages and then increase
      continuously with time of culture. Secondly, novel PKC isozymes delta, epsilon
      and zeta, whose contents increase very early to reach a maximum after three days
      of culture and then progressively decline. Specific proteolysis for PKC isozymes
      beta and gamma was observed throughout the period studied. The developmental
      profile obtained for the different PKC isozymes is discussed in relation to the
      differentiation of hippocampal neurones in culture.

PMID- 7737423
TI  - Reactivity of histidyl residues in D-amino acid oxidase from Rhodotorula
      gracilis.
AB  - Incubation of D-amino acid oxidase from the yeast Rhodotorula gracilis with
      excess dansyl chloride at pH 6.6 and 18 degrees C caused an irreversible
      inactivation of D-amino acid oxidase. Benzoate, a competitive inhibitor of the
      enzyme, completely protected the enzyme from inactivation. The dansylated-enzyme,
      isolated by gel-filtration, was in part still active while the substrate
      specificity was altered substantially. It was completely reduced by D-alanine in
      anaerobiosic conditions and did stabilize the red anion semiquinone upon
      photochemical reduction with EDTA. The results provide evidence for the presence
      of essential histidyl residue(s) in the active center of the yeast enzyme.

PMID- 7737425
TI  - 55th Annual meeting and scientific sessions of The American Diabetes Association.
      Atlanta, Georgia, June 10-13, 1995. Abstracts.

PMID- 7737426
TI  - The discipline of toxicology.

PMID- 7737424
TI  - A new function of Nm23/NDP kinase as a differentiation inhibitory factor, which
      does not require it's kinase activity.
AB  - We recently identified a differentiation inhibiting factor (I-factor) in mouse
      myeloid leukemia M1 cells as a murine homolog of nm23-H2/nucleoside diphosphate
      kinase (NDPK)-B gene product. We examined the I-factor activities of several
      authentic nm23/NDPK proteins, i.e. recombinant rat NDPK alpha and beta,
      recombinant mouse nm23-M1 and -M2, and recombinant human nm23-H1 and -H2
      containing a mutant nm23-H2His protein lacing NDPK activity. Almost all these
      nm23/NDPK proteins showed I-factor activity. Moreover, to understand the active
      domain exhibiting I-factor activity of nm23-H2 protein lacking NDPK activity, we
      have investigated the I-factor activities of some truncated nm23-H2 proteins. The
      truncated nm23-H2 protein containing N-terminal peptide 1-60 retained the I
      factor activity. These results provide the first evidence for a function of
      nm23/NDPK as a differentiation inhibiting factor in leukemic cells, that is
      independent of its NDPK activity and dependent on the presence of N-terminal
      peptide.

PMID- 7737427
TI  - Ozone-induced pulmonary functional, pathological, and biochemical changes in
      normal and vitamin C-deficient guinea pigs.
AB  - Since Vitamin C (ascorbate, AH2) is an important airway antioxidant and is an
      essential component of tissue repair, and since acute (4 hr) O3 toxicity is
      enhanced by AH2 deficiency, we hypothesized that longer-term O3 effects might
      also be increased. Female Hartley guinea pigs (260-330 g) were fed either an AH2
      sufficient or an AH2-deficient diet 1 week prior to exposure, and were maintained
      on their respective diets during 1 week of continuous exposure to O3 (0, 0.2,
      0.4, and 0.8 ppm, 23 hr/day), and during 1 week postexposure recovery in clean
      air. The AH2-deficient diet caused lung AH2 to drop to about 30% of control in 1
      week, and to below 10% by the end of exposure and recovery. Body weight gains
      during exposure were decreased in the 0.8 ppm O3 group, while the AH2 deficiency
      began to affect body weights only during recovery. O3 caused a concentration
      dependent decrease in total lung capacity, vital capacity, carbon monoxide
      diffusing capacity, nitrogen washout, and static compliance, while increasing
      forced expiratory flow rates and residual or end-expiratory volume (suggestive of
      pulmonary gas-trapping). The lung/body weight ratio and fixed lung displacement
      volume were also increased in O3-exposed animals. Lung pathology consisted of
      mononuclear cell and neutrophil infiltration, airway as well as alveolar
      epithelial cell hyperplasia, and general decrease in epithelial cell cytoplasm.
      Thickening of the interstitium and an apparent increase in collagen staining were
      seen at the terminal bronchiolar regions. Some of these effects were marginally
      exacerbated in AH2-deficient guinea pigs. One week postexposure to air reversed
      all O3-induced abnormalities, irrespective of AH2 deficiency. Whole lung
      hydroxyproline and desmosine were not changed at any time by either O3 or AH2
      deficiency. Measurement of lung prolyl hydroxylase activity suggested that AH2
      deficiency as well as O3 exposure may have increased the tissue levels of this
      enzyme. The lack of a significant increase in toxicity with the longer-term
      exposure scenario suggests that AH2 has minimal influence on other compensatory
      mechanisms developed over time.

PMID- 7737429
TI  - 2,5-Hexanedione exposure alters microtubule motor distribution in adult rat
      testis.
AB  - 2,5-Hexanedione (2,5-HD) exposure in rats causes a progressive Sertoli cell
      injury culminating in testicular atrophy. Morphological injury is preceded by
      alterations in the assembly characteristics of tubulin isolated from exposed rat
      testes. This is followed by decreased seminiferous tubule fluid (STF) secretion
      by Sertoli cells and an increase in the number and size of Sertoli cell vacuoles.
      The possible involvement of microtubules and microtubule motor-dependent
      transport processes in STF secretion by Sertoli cells prompted us to examine the
      immunodistribution of the microtubule motors cytoplasmic dynein and kinesin
      during and after 2,5-HD exposure in rats. Three weeks following the commencement
      of exposure (1% 2,5-HD in the drinking water), the intensity of apical Sertoli
      cell cytoplasmic dynein immunofluorescence declined. This staining deficit became
      statistically significant by 4 weeks of exposure. Accompanying this change, there
      was progressive disruption of the immunodistribution of cisternal Golgi elements
      and associated kinesin immunoreactivity. The decrease in apical Sertoli cell
      cytoplasmic dynein immunofluorescence and disruption of Golgi and kinesin
      immunoreactivity suggest that 2,5-HD-induced alterations in Sertoli cell-mediated
      transport and secretory events could involve deficits in microtubule-dependent
      motor function.

PMID- 7737428
TI  - Evaluation of auricular lymph node cell proliferation in isothiazolone-treated
      mice.
AB  - Chemicals that bind to protein may cause immunological responses that include
      allergic contact hypersensitivity mediated by T cells. Various animal models have
      been used to predict chemical-mediated contact sensitization. One assay that has
      recently been developed utilizes the proliferation response induced in the
      draining auricular lymph node after exposure to contact sensitizers. This assay
      has been modified to a simpler method that results in the more rapid processing
      of samples with greater reproducibility. Isothiazolones are chemicals used as
      biocides in various applications which at greater than use concentrations may
      cause allergic contact hypersensitivity. The mouse auricular lymph node cell
      proliferation assay has been used to examine the potential of various
      isothiazolones to induce contact sensitization. The extent of lymph node cell
      proliferation was dependent on the concentration of isothiazolone, the vehicle
      used in the application, and the ability of isothiazolone to bind to protein.
      Kathon biocide contains two isothiazolones: 5-chloro-2-methyl-4-isothiazolin-3
      one (CMI)2 and 2-methyl-4-isothiazolin-3-one (MI). In vivo studies have shown
      that protein binding correlates with auricular lymph node cell proliferation and
      an increase in auricular lymph node size. CMI, which binds to protein, induced an
      auricular lymph node cell proliferation response while MI, which poorly binds to
      protein, neither stimulated a proliferative response nor induced an increase in
      lymph node size at concentrations similar to CMI.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7737430
TI  - A comparison of the inflammatory response of the lung to inhaled versus instilled
      particles in F344 rats.
AB  - The potential pulmonary toxicity of poorly soluble airborne dusts generated in
      industrial and environmental settings is often evaluated by inhalation studies in
      rodents. Studies using intratracheal instillation of particles have been
      suggested as a less expensive alternative. We conducted a study to compare the
      inflammatory response of the lung to instilled versus inhaled particles. In one
      study, female F344/N rats, 11-13 weeks of age, were exposed for 6 hr/day, 5
      days/week for 4 weeks by inhalation to 0, 0.1, 1.0, or 10 mg/m3 of either alpha
      quartz (toxic particle) or TiO2 (relatively low toxicity particle) and the lung
      burdens were determined at 1 week after the end of the exposure. The lungs were
      evaluated by analysis of bronchoalveolar lavage fluid (BALF) at 1, 8, and 24
      weeks after the end of the exposure and by histopathology at 24 weeks. In a
      second study, rats were exposed by instillation to the lung burdens present in
      the preceding study at 1 week after the inhalation exposure, and the rats were
      evaluated in the same manner as in the inhalation study. In general, the degree
      of alveolitis, as evaluated by histopathology and BALF analysis, was similar by
      the two methods of exposure. With lung burdens up to 750 micrograms/g lung, the
      TiO2 elicited no changes in BALF parameters at any time by either method of
      exposure, nor was any histopathology observed. The BALF changes elicited by alpha
      quartz were of approximately the same magnitude and followed the same time course
      by either exposure method with the lowest dose delivered to the lung by either
      method being a "no-effect" dose. At the highest dose, microgranulomas were
      observed in bronchial-associated lymphoid tissue (BALT) in both sets of rats.
      However, the highest inhalation exposure induced pleural granulomatous lesions
      that were not observed in the animals instilled with alpha-quartz. The results
      indicate that the relative potentials of the two materials to produce
      bronchoalveolitis and granulomatous lesions in BALT could be appropriately
      evaluated using either intratracheal or inhalation exposures.

PMID- 7737433
TI  - Phenyl isocyanate-induced asthma in rats following a 2-week exposure period.
AB  - This study was conducted to assess the toxic effects of repeated inhalation
      exposures to phenyl isocyanate vapor in male Wistar rats. Rats were exposed to
      design concentrations of 0, 1, 4, 7, or 10 mg/m3 phenyl isocyanate air for 2
      weeks (6 hr/day, 5 days/week). The rats were assessed for normal toxicologic
      parameters, and pulmonary function tests, blood gas measurements, and analysis of
      bronchoalveolar lavage fluid (BALF) parameters were utilized shortly after
      exposures as well as 2 months postexposure. The results indicated that rats
      exposed to 7 and 10 mg/m3 experienced decreased body weights, hypoactivity,
      hypothermia, signs of respiratory tract irritation, delayed onset of mortality,
      and changes in organ weights. In addition, pulmonary function tests demonstrated
      decreased forced expiratory flow rates and quasistatic lung compliance. Arterial
      blood gases showed an arterial hypoxemia and changes consistent with a pronounced
      venous-admixture-like perfusion, suggesting severe mismatch of the
      ventilation/perfusion relationship. Delayed onset of mortality appeared to be
      associated with respiratory acidosis and hypoxemia. Biochemical and cellular
      components in BALF complemented the results of the functional alterations.
      Remarkable changes were indicated by increased activities of the BALF parameters,
      gamma-GPT, protein, and sialic acid. Histopathological findings provided evidence
      of increased secretory cell activity and a concentration-dependent increase in
      goblet cell hyperplasia at concentrations of 4 mg/m3 and above. In rats exposed
      to 7 mg/m3 further findings consisted of intraluminal inflammation of airways,
      hypertrophia of bronchial smooth muscle, epithelial desquamation, and
      eosinophilia of the airways. A complete regression of morphological lesions was
      not found in the animals exposed to 4 mg/m3 and above at the 2-month postexposure
      time period. In conclusion, the damage to the airways comprise most of the
      features characteristic of chronic airway inflammation or asthma.

PMID- 7737432
TI  - A two-generation reproduction study in rats receiving drinking water containing
      vinyl acetate.
AB  - Vinyl acetate (VA) is a commonly used chemical in polymerization and
      copolymerization processes and as a chemical intermediate. As part of a
      collaborative effort between VA producers of the United States and British
      Petroleum, the present study was carried out to provide a base set of data for
      risk assessment. Groups of male and female Crl:CD(SD)BR rats were given 0, 200,
      1000, or 5000 ppm VA via the drinking water over two generations. In addition, a
      cross-mating trial of control and 5000-ppm male and female rats was conducted in
      the F1 generation to investigate the slightly decreased litter production in the
      high-dose group. No treatment-related mortality was observed in any of the
      groups. Water consumption was significantly reduced in the 5000-ppm groups in
      both generations and in the 1000-ppm F1 female rats. The body weights of the F0
      and F1 male rats and the F1 female rats in the 5000-ppm group tended to be
      slightly lower than those of the control group. Body weight gain was
      significantly decreased during lactation in the F0 females at 5000 ppm and in the
      F1 females at 1000 and 5000 ppm. Pup weights in the F1 generation, but not in the
      F2 generation, were significantly lower than those of the control on lactation
      Day 21. The number of litters produced in the F1 generation in the 5000-ppm group
      was slightly lower than that of the control group and was attributed to lower
      fertility. Fewer pups were produced when control females were mated with the 5000
      ppm males; however, the decrease was due to poor mating performance rather than
      decreased fertility. No decrease was apparent when the 5000-ppm females were
      mated with the control group males. Under the conditions of this study, the no
      observed adverse effort level was considered to be 1000 ppm.

PMID- 7737434
TI  - Disposition of ingested olestra in the Fischer 344 rat.
AB  - Four studies were conducted in the Fischer 344 rat to determine the disposition
      of orally gavaged olestra. Twenty-four rats were used for each study. Three
      olestra samples, differing in the degree of saturation of the fatty acid chains,
      were tested; one sample was heated to simulate olestra's intended use in
      preparing fried foods. In addition, a sucrose polyester (SPE) sample containing
      28% short-chain penta- and lower polyesters was tested. All test samples were
      uniformly labeled with 14C in the sucrose moiety. Urine, feces, and CO2 were
      continuously collected and counted. Urine also was analyzed for [14C]sucrose by
      HPLC. If olestra were absorbed and systemically metabolized, [14C]sucrose would
      be excreted in the urine. Rats were killed 1, 3, 7, and 21 days after dosing, and
      tissues were collected and counted. Tissue lipids were extracted and analyzed for
      intact olestra or SPE by HPLC. Less than 0.15% of the dose of 14C was absorbed
      from the olestra samples, and about 1.3% from the SPE sample. The disposition of
      the absorbed radiolabel suggested that its source was glucose and fructose
      resulting from the intestinal hydrolysis of short-chain penta- and lower sucrose
      polyesters. For rats dosed with olestra, < 8 x 10(-4)% of the dose of radiolabel
      was recovered in the olestra-containing fraction of lipids extracted from liver,
      the target organ for absorbed olestra, and no [14C]sucrose was found in urine,
      indications that olestra essentially was not absorbed. Heating olestra did not
      change this result.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737435
TI  - Optimization and validation of an ELISA to measure specific guinea pig IgG1
      antibody as an alternative to the in vivo passive cutaneous anaphylaxis assay.
AB  - Assessment of the allergenic potency of enzymes involves the use of a guinea pig
      model in which specific IgG1 antibody titers are used as the endpoint. The in
      vivo passive cutaneous anaphylaxis (PCA) assay is used to measure specific IgG1
      antibody. This report describes the development and validation of an enzyme
      linked immunosorbent assay (ELISA) to measure guinea pig specific IgG1 antibody
      as an in vitro alternative to the PCA assay. Cross reactivity of various rabbit
      and mouse (monoclonal) anti-guinea pig IgG1 preparations were evaluated using
      purified IgG1 and IgG2 from serum of guinea pigs immunized with ovalbumin. The
      two subclasses of guinea pig IgG were purified by first using Protein A affinity
      chromatography, followed by anion exchange chromatography and fluid phase
      isoelectric focusing. Affinity-purified rabbit anti-guinea pig IgG1 was shown to
      have minimal cross reactivity toward IgG2, while providing a strong signal with
      IgG1. The ELISA was designed as an antigen capture system in which the following
      are added in sequence: (1) enzyme antigen (passively adsorbed to the plate), (2)
      diluted serum samples from guinea pigs immunized with enzyme, (3) affinity
      purified rabbit anti-guinea pig IgG1, (4) alkaline phosphatase-conjugated donkey
      anti-rabbit IgG, and (5) p-nitrophenyl phosphate substrate. Three replicate ELISA
      and PCA analyses were conducted on sera samples of varying titers from guinea
      pigs immunized with either Alcalase (protease), BPN' (protease), and Termamyl
      (amylase) enzyme. The correlation coefficients (r2) between the ELISA and PCA
      assay for Alcalase, BPN', and Termamyl were 0.826, 0.945, and 0.755,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737431
TI  - Developmental toxicity of oral and inhaled vinyl acetate in the rat.
AB  - Vinyl acetate (VA) is used almost exclusively as an industrial chemical in
      polymerization, copolymerization, or as a chemical intermediate. The present
      studies were undertaken as part of a collaborative effort by the VA producers of
      Western Europe, Japan, and the United States to provide animal toxicology data
      for risk assessment. To assess the potential of VA causing developmental toxicity
      in rodents, groups of 23 or 24 Crl:CD(SD)BR rats were given 0, 200, 1000, or 5000
      ppm VA in drinking water or exposed 6 hr/day to 0, 50, 200, or 1000 ppm VA vapors
      on Days 6-15 of gestation (both routes approximately 0, 25, 100, or 500
      mg/kg/day). Administration of VA in the drinking water produced no evidence of
      maternal or developmental toxicity. A significantly lowered water intake was
      observed in dams from the 5000 ppm VA group and probably reflected unpalatability
      of the VA water solution at the highest dose level. In the inhalation study,
      maternal toxicity was evident by a marked reduction in weight gain of dams
      exposed to 1000 but not 200 or 50 ppm VA. Fetal toxicity was evident by a
      statistically significant decrease in mean fetal weight and mean crown-rump
      length in fetuses from the 1000-ppm VA group. In addition, there was a
      statistically significant increase in the incidence of minor skeletal alterations
      in fetuses from dams exposed to 1000 ppm VA. Delayed ossification was the main
      skeletal alteration. In summary, pregnant rats were relatively insensitive to the
      effects of VA administered in the drinking water at a concentration level as high
      as 5000 ppm. However, VA did adversely affect both the dam and the conceptus at
      an inhaled concentration of 1000 ppm, but not at lower exposure levels. These
      results indicate that VA is not uniquely toxic to the conceptus. The no-observed
      effect level for the dam and conceptus under these experimental conditions was
      greater than 5000 ppm for the drinking water study and was 200 ppm for the
      inhalation study.

PMID- 7737436
TI  - The effect of body weight on tumor incidence and carcinogenicity testing in
      B6C3F1 mice and F344 rats.
AB  - Associations between animal body weights and tumor incidence were examined using
      individual control animal data from 55 mouse and 53 rat studies conducted by the
      National Toxicology Program. Several statistically significant associations were
      found, the strongest of which were positive relationships between body weight and
      risk of liver tumors in both sexes of mice, pituitary gland tumors in both sexes
      of rats, and mammary gland tumors in female rats. The most compelling evidence
      that these relationships were causal in nature was the replication of the
      correlations across individual experiments. In addition, significant correlations
      between tumor occurrence and body weights occurred in animals as young as 9 weeks
      of age. Logistic regression models relating 12-month body weight to tumor risk
      were developed for the strongest relationships, and utilized in the reanalysis of
      tumor data from two National Toxicology Program studies with treatment-related
      decreases in body weight. A simulation study based on the logistic regression
      models indicated that statistical power to detect a treatment-related increase in
      tumor incidence can be seriously diminished when mean body weight in treated
      animals is depressed by as little as 10%. Conversely, when mean body weight in
      control animals is 10% lower than that of treated animals, false positive rates
      can increase to 20-30%. The severity of the effects of such commonly observed
      treatment-related disparities in body weight suggests that alternative data
      analysis methods or experimental designs should be considered to address this
      potential problem in carcinogenicity testing.

PMID- 7737437
TI  - Immunohistochemical localization of acetaminophen in target tissues of the CD-1
      mouse: correspondence of covalent binding with toxicity.
AB  - Administration of hepatotoxic doses of acetaminophen (APAP) to mice results in
      necrosis, not only of liver cells but of renal proximal tubules and bronchiolar
      and olfactory epithelium. In the liver, covalent binding is localized to the
      centrilobular hepatocytes which later undergo necrosis. This study was undertaken
      to compare the cellular distribution of bound APAP in all four major target
      tissues with that of cytochrome P4502E1 (a P450 isoenzyme commonly associated
      with APAP bioactivation), with emphasis on the cell types which later undergo
      necrosis. Tissues were collected from mice at selected times after APAP
      administration (600 mg/kg, po) and fixed by microwave irradiation for
      immunohistochemistry, or in formalin for histopathological study.
      Immunohistochemical localization of bound APAP was performed on 5-microns
      paraffin sections using an affinity-purified anti-APAP antibody. Similar tissues
      from naive mice were used for immunohistochemical localization of cytochrome
      P4502E1 (using a polyclonal sheep anti-P4502E1 antibody). Positive staining with
      both the anti-APAP and the anti-P4502E1 antibodies was similar in distribution,
      being present in the cell types which become damaged by APAP in all four target
      tissues. These results demonstrate that covalent binding and subsequent necrosis
      are localized in common with cytochrome P4502E1, suggesting that, as in the
      liver, toxicity in extrahepatic targets is also related to the ability of these
      tissues to activate APAP in situ.

PMID- 7737439
TI  - Host resistance to Trichinella spiralis infection in rats exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD).
AB  - We have previously shown decreased resistance to Trichinella spiralis (Ts)
      infection and reduced parasite antigen-specific responses in B6C3F1 mice exposed
      to TCDD before infection. The current study was done to characterize the effects
      of preinfection administration of 1, 10, or 30 micrograms TCDD/kg on host
      resistance of female F344 rats to Ts infection and to examine parasite antigen
      specific responses in the spleen and mesenteric lymph nodes of infected animals.
      TCDD exposure did not affect adult parasite elimination from the small intestine
      or the numbers of encysted larvae in the muscle, although host control of newborn
      larvae production in female parasites isolated from the highest dose group was
      compromised. Proliferative responses of lymphocytes cultured with parasite
      antigen were enhanced in groups of rats exposed to 30 micrograms TCDD/kg. These
      results, which are in marked contrast to the effects obtained in B6C3F1 mice,
      demonstrate a clear species difference in the effects of TCDD on immune function
      in rodents and underscore the need to determine which species more closely
      reflects the potential outcome of human exposure to TCDD.

PMID- 7737438
TI  - The effect of methadone on the immune status of B6C3F1 mice.
AB  - Previously, morphine has been shown to elevate corticosterone via the
      hypothalamic-pituitary-adrenal axis and to suppress the immune system. The
      present investigation sought to determine if the mu-opiate receptor agonist
      methadone incurred a similar immune suppression in B6C3F1 mice. Serum methadone
      and corticosterone levels peaked 1 hr following a single subcutaneous injection
      of 20 mg/kg methadone HCl. Indeed, the rise in corticosterone levels paralleled
      that of methadone. After a single injection with 20 mg/kg methadone a
      pharmacokinetic analysis revealed a serum half-life of approximately 2 hr.
      Following five injections of methadone over a 24-hr period (every 6 hr),
      methadone levels were elevated as would be expected; however, corticosterone
      levels did not become elevated. This suggests that the ability of methadone to
      elevate corticosterone becomes uncoupled following repeated dosing, indicative of
      either a tolerance or an increased catabolic mechanism. Moreover, dosing every 6
      hr for 5 days induced an increase in the catabolism of methadone itself.
      Therefore, all assays were begun 1 hr after subcutaneous administration of
      methadone HCl, a time at which both methadone and corticosterone serum levels
      were elevated. The primary IgM antibody response to sheep red blood cells (sRBC)
      was suppressed when splenocytes were immunized in vitro. In contrast, animals
      immunized with sRBC and assayed for the primary IgM antibody response 4 days
      later were not suppressed. The activity of the resident macrophages of the liver
      and spleen as measured by the uptake of 51Cr-sRBC was suppressed in a dose
      dependent manner. Previously, it has been demonstrated that morphine suppresses
      hepatic and splenic phagocytic activity through an opiate receptor-mediated
      pathway that involves the release of corticosterone. It would appear that
      methadone plays a similar role in the suppression of hepatic and splenic
      phagocytosis.

PMID- 7737440
TI  - Re: Dose as central variable in toxicology.

PMID- 7737441
TI  - Behavioral scientists' views on work environment, roles, and teaching.
AB  - BACKGROUND: In earlier years, the majority of behavioral scientists in family
      medicine were physicians. Recent data suggest that the vast majority now come
      from disciplines outside of medicine. Little is known about how behavioral
      scientists view their work environments, which roles and teaching approaches are
      used most often, and if these variables change among groups with different
      amounts of experience. METHODS: Data from a survey mailed to 384 family practice
      residencies addressed four objectives, to: 1) collect behavioral scientists'
      demographic data, 2) assess behavioral scientists' perceptions of their work
      environments, 3) measure frequency of use of teaching approaches, and 4) measure
      frequency of assuming different roles among groups with different amounts of
      experience. RESULTS: Behavioral scientists from 214 of the 384 surveyed programs
      responded, for a total response rate of 56%. An additional 15 program directors
      (4%) reported no behavioral scientist on their faculty. Relative time allocation
      for various roles was the same in the three experience groups; the most emphasis
      was placed on consultation and teaching. One-on-one teaching was the teaching
      modality used most frequently. Case-based teaching was used more in experienced
      groups. Behavioral scientists felt strongly supported by faculty and moderately
      supported by residents. CONCLUSIONS: This study's results offer insight into how
      behavioral scientists spend their time and the teaching approaches they use most
      frequently. The relationship between behavioral scientists' years of experience
      and teaching approaches is examined. Behavioral scientists stay in their jobs
      longer and feel more included than their earlier cohorts in family medicine.

PMID- 7737442
TI  - Family practice center-based training in skin disorders: a photographic approach.
AB  - BACKGROUND: The majority of family practice residency programs rely on lectures
      and rotations in dermatologists' offices for training their residents about skin
      disorders. However, in a dermatologist's office, residents may not receive enough
      exposure to the types of skin problems typically seen in a family physician's
      office. METHODS: A longitudinal, family practice center-based training experience
      was developed in which residents photographed patients with skin conditions and
      presented the cases to a dermatologist at a monthly teaching conference. Fifteen
      residents who were exposed to two different instructional methods (the
      photography conference and rotations with dermatologists) were surveyed to
      determine their preferred instructional method for learning to diagnose and
      manage skin disorders. RESULTS: Over a 2-year period, a total of 232 skin lesions
      were photographed and presented. The distribution of the photographed skin
      disorders differed from the distribution of skin problems found in a national
      survey of dermatologists' practices. Of the residents surveyed, 93% preferred
      monthly photography conferences to rotations in dermatologists' offices for
      learning about children's skin problems. Eighty-six percent preferred using the
      photography conferences for learning about treatment of skin diseases.
      CONCLUSIONS: A longitudinal, family practice center-based experience using
      photographic presentations of skin lesions is a valuable adjunct for teaching
      family practice residents about skin disorders.

PMID- 7737443
TI  - Trend analysis of changes in family practice residency graduates' practice
      characteristics and comparison with recent graduates.
AB  - BACKGROUND AND OBJECTIVES: Graduate follow-up studies provide medical educators
      with important evaluation information and insight into graduates' practices. This
      study compares early practice choices of two cohorts of family practice residents
      who graduated a decade apart. The earlier cohort's changes in practice
      characteristics over a 10-year period were also analyzed. METHODS: Using a mailed
      survey, graduates of the University of California-Davis Family Practice Residency
      Network have been periodically surveyed since 1978. Using data from these
      surveys, early practice choices of the two cohorts were compared. In addition,
      the responses of the earlier cohort were tracked over time to determine whether
      any early practice patterns still existed. RESULTS: Significant differences in
      the early practice choices of the two cohorts of graduates were found in the
      areas of practice organization, use of mid-level practitioners, perception of
      need for primary care physicians, and inclusion of pregnancy care in practice. A
      significantly lower percentage of recent graduates had entered private practice,
      compared with the earlier cohort (37% vs 50%, P = .02). Recent graduates were
      more likely to perceive a need for primary care physicians. Finally, the early
      practice choice differences between the two cohorts had all but disappeared 10
      years later as the earlier cohort's practices had changed to resemble more
      closely those of the recent graduates. CONCLUSIONS: This study concludes that the
      practices of both established family physicians and recent graduates are
      changing. Residency faculty must understand how these changes influence the skill
      and knowledge needs of their future graduates and should design practice
      management curricula accordingly.

PMID- 7737444
TI  - Enhancing compliance with screening mammography recommendations: a clinical trial
      in a primary care office.
AB  - BACKGROUND AND OBJECTIVES: Despite consensus that screening mammography is an
      appropriate preventive tool, many women do not receive this examination. This
      study was undertaken to evaluate the relative efficacy and cost-effectiveness of
      three interventions designed to increase mammography rates. METHODS: A total of
      151 women, aged 50-59, were randomized into four groups: control, physician
      telephone call, medical assistant telephone call, and physician letter. RESULTS:
      The women in the medical assistant telephone call group (16 of 37 = 43%) and the
      physician telephone call group (11 of 38 = 29%) responded significantly better
      than those in the control group (4 of 38 = 11%) (P < .05). None of the 10 widows
      in the entire study obtained a mammogram, compared with 38 of 141 (27%) women in
      all other marital groups (P < .05). The cost per intervention and cost per
      mammogram obtained were, respectively, physician telephone call: $15, $51.82;
      physician letter: $2.50, $13.57; medical assistant call: $1.30, $3. CONCLUSIONS:
      Medical assistant telephone callers are a cost-effective strategy to encourage
      mammography adherence. Widows appear particularly resistant to all screening
      mammography interventions.

PMID- 7737445
TI  - Prevalence of cigarette and smokeless tobacco use among students in rural Oregon.
AB  - BACKGROUND: Although smoking and smokeless tobacco use are recognized as major
      problems among school-age youth, few studies report on tobacco use in rural
      areas, especially remote rural areas. METHODS: A self-report questionnaire was
      administered to all junior and senior high school students from a frontier rural
      community. RESULTS: A total of 393 students completed the questionnaire. Of the
      393, 39% had tried chewing tobacco at least once. High school males were the
      heaviest users, and more than 50% of those males who had ever chewed were still
      current users (33% of the town's high school males). Seven percent of the town's
      high school females used chewing tobacco, one of the country's highest reported
      rates of use at the time of this study. In addition, 39% of all the students had
      also smoked cigarettes. High school females reported the highest prevalence of
      ever having smoked (52%) and also had the highest prevalence of current smoking
      (13.5%). The number of students who had ever tried any form of tobacco use and
      the number who were current users were significantly higher in the high school
      than the junior high school. More than half of the students who smoked or chewed
      reported having close friends who also use tobacco products. CONCLUSION: The high
      rate of female smokers and male chewers in senior high is consistent with other
      studies. The rate of female chewing tobacco use is unusually high. Isolated rural
      communities have significant adolescent tobacco abuse, and prevention and
      treatment strategies need to be developed for this special population.

PMID- 7737446
TI  - Stability of standardized patients' performance in a study of clinical decision
      making.
AB  - BACKGROUND: Standardized patients (SPs) have been used extensively in teaching,
      but their reliability for use in research has been infrequently addressed. This
      study analyzes the reliability of performance of 13 SPs during 228 doctor-patient
      encounters in a year-long study related to the diagnosis of depression. METHODS:
      Patient scenarios were based on real patient cases. Four of the five cases had
      major depressive disorder. Two to three SPs were coached to enact each of the
      five case scenarios. Medical encounters were videotaped. Interview content was
      extracted onto a standardized checklist. Interaction between physician and
      patient was measured by the Interactional System for Interview Evaluation. Tests
      of SP performance reliability included the: 1) consistency of symptoms
      volunteered, 2) stability of affect and behavior, and 3) association of SP
      performance to detection of depression. RESULTS: The mean number of SP
      performances was 20.8 (SD = 5.8), with a range of 6 to 28. Problems with
      reliability emerged in one of the five patient cases. Results otherwise revealed
      high intra-performance and inter-performance reliabilities. Detection of
      depression was consistent across SPs and with the rates reported in the
      literature. CONCLUSIONS: This study provides evidence that performances, within
      and among SPs, remained consistent, even when intervals between performances were
      as long as 3 months.

PMID- 7737447
TI  - Family-centered birthing: history, philosophy, and need.

PMID- 7737448
TI  - The death of academic family medicine: can it be prevented?

PMID- 7737449
TI  - Occupational exposures in family practice residency programs.

PMID- 7737450
TI  - Family medicine must mobilize to respond to changed environment.

PMID- 7737451
TI  - Defining the need for faculty in family medicine: results of a national survey.
AB  - BACKGROUND: Although numerous anecdotal reports are being offered about the
      growing number of unfilled faculty positions in US family medicine departments,
      virtually no literature exists on faculty recruitment. The objective of this
      study was to define the scope and nature of current faculty recruitment needs in
      family medicine. METHODS: A national survey was sent to all family medicine
      department chairs and family practice residency program directors concerning
      faculty positions unfilled at their sites and positions for which recruitment
      would occur within the next 5 years. The survey asked for information on
      currently available positions; academic title of position; percentage of time to
      be devoted to clinical, educational, administrative, and research activities;
      primary focus of the position; date when the position became available; and the
      length of time the position has been unfilled. Similar information was collected
      on positions anticipated to be available within the next 5 years. RESULTS: A
      total of 364 surveys were returned, for an overall response rate of 70%.
      Information from the survey revealed a current, substantial demand for family
      medicine faculty throughout the country, with an even greater demand anticipated
      for the near future. Respondents reported 496 currently unfilled positions for
      family medicine faculty and another 677 positions anticipated to be available
      within the next 19.5 months on average. A total of 89.7% of those anticipated
      positions were reported as either "certain" or "somewhat certain," in terms of
      likelihood of availability. CONCLUSIONS: The demand for family medicine faculty
      is increasing, and much of the demand is financially motivated. Clinical
      expectations appear to be higher among departments than for residencies. Finally,
      it was revealed that most positions had minimal allotments for research time.
      Family medicine must recommit itself to the development of a scholarly agenda as
      it recruits new faculty.

PMID- 7737453
TI  - The Internet biologist.

PMID- 7737452
TI  - The other AIDS crisis.

PMID- 7737454
TI  - Introduction: flavoprotein structure and mechanism.

PMID- 7737455
TI  - Structure and mechanism of para-hydroxybenzoate hydroxylase.
AB  - Para-hydroxybenzoate hydroxylase (EC 1.14.13.2) is a flavoprotein involved in
      degradation of aromatic compounds, and it has become a model for enzymes involved
      in the oxygenation of a substrate. The chemical and kinetic mechanisms of this
      enzyme are described and integrated with an outline of the structure of the
      protein from crystallographic analysis. The structure is unusual because there is
      no recognizable domain for the binding of NADPH involved in the reaction.
      Recently, mechanistic studies of site-directed mutants, combined with structural
      analyses, have provided some exciting discoveries about protein function. The
      substrate during catalysis is largely isolated from solvent in the active site, a
      necessary condition for successful product formation. The flavin ring structure
      moves substantially in the active site, probably to enable substrate and product
      exchange into this site and possibly to regulate the reduction of the flavin by
      NADPH. A chain of H-bonds can connect p-hydroxy-benzoate in the active site of
      the enzyme with the protein surface. This chain is responsible for the reversible
      formation of substrate phenolate anion observed in the active site and partly
      responsible for the reactivity of this substrate.

PMID- 7737456
TI  - Protein kinase C and lipid signaling for sustained cellular responses.
AB  - Since the second messenger role was proposed for the products of inositol
      phospholipid hydrolysis, considerable progress has been made in our understanding
      of the biochemical mechanism of the intracellular signaling network. It is now
      becoming evident that stimulation of a cell surface receptor initiates a
      degradation cascade of various membrane lipid constituents. Many of their
      metabolites have potential to induce, intensify, and prolong the activation of
      protein kinase C that is needed for sustained cellular responses.

PMID- 7737457
TI  - The structure and evolution of alpha/beta barrel proteins.
AB  - Roughly 10% of all known enzyme structures have an alpha/beta barrel domain. The
      members of this large family of proteins catalyze very different types of
      reactions. Such diversity of function has made this family a target for protein
      engineering. The evolutionary history of this family has been the subject of
      vigorous debate. In this paper, arguments are made to support the divergence of
      all members of this family from a common ancestor. Because of the lack of strong
      sequence homology, the ancestral molecule must be very old. A hypothesis
      concerning the relationship between chemical mechanism and evolutionary history
      is discussed. Evidence is presented to suggest that convergent molecular
      evolution occurs when there is only one energetically reasonable pathway for a
      chemical reaction.

PMID- 7737458
TI  - Mercury exposure from "silver" tooth fillings: emerging evidence questions a
      traditional dental paradigm.
AB  - For more than 160 years dentistry has used silver amalgam, which contains
      approximately 50% Hg metal, as the preferred tooth filling material. During the
      past decade medical research has demonstrated that this Hg is continuously
      released as vapor into mouth air; then it is inhaled, absorbed into body tissues,
      oxidized to ionic Hg, and finally covalently bound to cell proteins. Animal and
      human experiments demonstrate that the uptake, tissue distribution, and excretion
      of amalgam Hg is significant, and that dental amalgam is the major contributing
      source to Hg body burden in humans. Current research on the pathophysiological
      effects of amalgam Hg has focused upon the immune system, renal system, oral and
      intestinal bacteria, reproductive system, and the central nervous system.
      Research evidence does not support the notion of amalgam safety.

PMID- 7737459
TI  - Chloride channels: a state of flux.
AB  - Chloride channels play important functions in different aspects of cell
      physiology including volume regulation, transepithelial ion transport and
      stabilization of membrane potential. In recent years the molecular identity of
      the chloride channels defective in cystic fibrosis and myotonia congenita has
      been elucidated, highlighting the importance of anion-selective channels in cell
      and tissue function. Concurrently, several proteins have been identified as
      chloride channels along with proteins that possess channel regulatory behavior.
      Novel interactions with more potent pharmacological compounds have been reported
      with different chloride channels. This burgeoning field of interest is reviewed.

PMID- 7737460
TI  - Molecular biology and pharmacology of cloned opioid receptors.
AB  - The cloning and expression of DNA for the three major opioid receptor types (mu,
      delta, and kappa) present new research opportunities for the characterization of
      opioid drugs and their interactions with these receptors. Genomic and cDNA clones
      for opioid receptors exist for several animal species including mouse, rat,
      guinea pig, and human. These include clones for all three human opioid receptor
      types. The receptor proteins consist of about 400 amino acids and have the
      characteristic seven transmembrane domain structure of G-protein-coupled
      receptors. There is about 60% amino acid identity between opioid receptor types
      and about 90% identity between a receptor type cloned from different animal
      species. All opioid receptor types mediate the inhibition of adenylyl cyclase in
      response to agonist binding. Radioligand binding and functional studies using the
      cloned receptors tend to support current conclusions on opioid drug receptor
      selectivity and activity. Investigations of opioid receptor chimeras and single
      amino acid mutants are providing information on the ligand recognition sites of
      these receptors and essential support for the development of computational opioid
      receptor models. A molecular model of the human delta opioid receptor is included
      in this review.

PMID- 7737461
TI  - Oxidative processes and antioxidative defense mechanisms in the aging brain.
AB  - The debilitating consequences of age-related brain deterioration are widespread
      and extremely costly in terms of quality of life and longevity. One of the
      potential major causes of age-related destruction of neuronal tissue is toxic
      free radicals that are a natural result of aerobic metabolism. The brain is
      particularly susceptible to free radical attack because it generates more of
      these toxicants per gram of tissue than does any other organ. The major defense
      mechanisms the brain uses to combat reducing equivalents is via their enzymatic
      metabolism. The vitamin antioxidants, vitamin E (alpha-tocopherol in particular)
      and vitamin C (ascorbate), also aid in protecting the brain from oxidative stress
      by directly scavenging toxic radicals. A newly discovered, potentially highly
      important antioxidant in the brain is the indole melatonin. The pineal hormone
      melatonin is rapidly taken up by the brain. In vitro melatonin is more effective
      than glutathione in scavenging the highly toxic hydroxyl radical and also more
      efficient than vitamin E in neutralizing the peroxyl radical. Furthermore, it
      stimulates the main antioxidant enzyme of the brain, glutathione peroxidase. In
      vivo melatonin is a potent antioxidant and it lacks prooxidant actions.

PMID- 7737462
TI  - The hydrophobic effect in protein folding.
AB  - In this review of protein folding we consider the noncovalent interactions
      existing between atoms or molecules at the molecular level. The electrostatic,
      Van der Waals, hydrogen bonding, and hydrophobic interactions are described and
      their contribution to protein conformation is discussed. The growing interest in
      the hydrophobic effect arises from its importance in the protein folding process,
      and a semiempirical simulation of the free energy of solvation is proposed. In
      most proteins, the different forces we describe contribute to the stability of
      the protein conformation in a complex way. However, in the case of the
      apolipoproteins and cytochrome C551, the energetic contributions are easily
      distinguished. For this reason, these proteins are used to illustrate the
      importance of the different energy fields.

PMID- 7737463
TI  - Inhibition of fatty acid and cholesterol synthesis by stimulation of AMP
      activated protein kinase.
AB  - AMP-activated protein kinase is a multisubstrate protein kinase that, in liver,
      inactivates both acetyl-CoA carboxylase, the rate-limiting enzyme of fatty acid
      synthesis, and 3-hydroxy-3-methyl-glutaryl-CoA reductase, the rate-limiting
      enzyme of cholesterol synthesis. AICAR (5-amino 4-imidazolecarboxamide ribotide,
      ZMP) was found to stimulate up to 10-fold rat liver AMP-activated protein kinase,
      with a half-maximal effect at approximately 5 mM. In accordance with previous
      observations, addition to suspensions of isolated rat hepatocytes of 50-500
      microM AICAriboside, the nucleoside corresponding to ZMP, resulted in the
      accumulation of millimolar concentrations of the latter. This was accompanied by
      a dose-dependent inactivation of both acetyl-CoA carboxylase and 3-hydroxy-3
      methylglutaryl-CoA reductase. Addition of 50-500 microM AICAriboside to
      hepatocyte suspensions incubated in the presence of various substrates, including
      glucose and lactate/pyruvate, caused a parallel inhibition of both fatty acid and
      cholesterol synthesis. With lactate/pyruvate (10/1 mM), half-maximal inhibition
      was obtained at approximately 100 microM, and near-complete inhibition at 500
      microM AICAriboside. These findings open new perspectives for the simultaneous
      control of triglyceride and cholesterol synthesis by pharmacological stimulators
      of AMP-activated protein kinase.

PMID- 7737464
TI  - The ion parametric resonance model predicts magnetic field parameters that affect
      nerve cells.
AB  - An ion parametric resonance (IPR) model recently developed by Blanchard and
      Blackman predicts distinct magnetic field interactions with biological systems
      based on a selective relation among four factors: the flux density of the static
      magnetic field, the frequency and flux density (Bac) of the parallel ac magnetic
      field, and the charge-to-mass ratio of ions of biological relevance. To test this
      model, PC-12 cells stimulated by nerve growth factor to produce neurites were
      exposed for 23 h in a 5% CO2 incubator using a multiple-coil exposure system to
      produce 45 Hz ac and dc (366 mG parallel to ac; less than 2 mG perpendicular to
      ac) magnetic fields. Our earlier work showed a cycle of inhibition/no inhibition
      of neurite outgrowth consistent with the IPR model predictions for Bac exposures
      between 0 and 468 mG rms. The work described here tests neurite outgrowth over a
      broader range of Bac (233-1416 mG rms). The experimental results remain
      consistent with earlier results, and with IPR model predictions of a second cycle
      of inhibition, return to control values, followed by a third cycle of inhibition
      of neurite outgrowth. These responses support the fundamental relationships
      predicted by the IPR model. The results have broad significance for biology.

PMID- 7737465
TI  - Nitric oxide and cGMP analogs activate transcription from AP-1-responsive
      promoters in mammalian cells.
AB  - Nitric oxide (NO) increases cytosolic guanylate cyclase activity and thereby
      activates the cGMP signal transduction pathway. The cAMP and Ca2+/phospholipid
      signal transduction pathways activate transcription factors that bind to the cAMP
      response element (CRE) and phorbol ester response element (TRE), respectively.
      Little is known about transcriptional regulation of gene expression by NO/cGMP.
      In transient and stable transfection experiments and in microinjection studies we
      found that three different NO-releasing agents and two membrane-permeable cGMP
      analogs activated TRE-regulated but not CRE-regulated reporter genes in rodent
      fibroblast and epithelial cell lines. Activation of TRE-regulated genes by NO
      releasing agents and cGMP analogs appeared to be mediated by the AP-1 (Jun/Fos)
      transcription factor complex because we observed increased DNA binding of AP-1
      and increased junB and c-fos mRNA in cells treated with these agents. The
      mechanism of gene activation by NO/cGMP was distinct from that used by phorbol
      esters and cAMP because it was not associated with c-jun mRNA induction and was
      not observed with CRE-containing promoters.

PMID- 7737466
TI  - From human serum albumin to rotational catalysis by ATP synthase.

PMID- 7737467
TI  - The up-and-down beta-barrel proteins: three of a kind.

PMID- 7737468
TI  - Defense.

PMID- 7737469
TI  - Bradyrhizobium japonicum nodulation genetics.
AB  - Studies of the genetics of nodulation by Bradyrhizobium japonicum have revealed
      many similar features with Rhizobium and Azorhizobium species, but also apparent
      differences. The regulation of nod gene expression in B. japonicum is complex,
      involving the interplay of the positive regulator, NodD1, as well as a repressor,
      No1A. A unique feature of B. japonicum is the involvement of a two-component
      regulatory system, NodV and NodW, in the control of nod gene expression. It is
      not clear why B. japonicum requires this level of complexity to control nod gene
      transcription. The nod gene products encode the biosynthesis of substituted lipo
      chitin Nod signals that induce many of the early nodulation events. B. japonicum
      and B. elkanii produce a large variety of such Nod signals. The basic structure
      of the Nod signal, an acylated oligomer of N-acetylglucosamine, is synthesized
      through the action of NodA, NodB, and NodC. Various substitutions of this basic
      structure confer host specificity to the molecule. For example, in B. japonicum,
      the nodZ gene product is essential for fucosylation of the terminal, reducing N
      acetylglucosamine residue. These observations argue for the interaction of a
      substituted Nod signal with a specific plant receptor molecule. However,
      structure/function studies using chemically synthesized Nod signal molecules
      suggest a more complex interaction between chain length and specific
      substitution. These findings leave open the possibility that a general chitin
      receptor may function in a unique way to elicit nodule formation. The novel
      features discovered through the study of B. japonicum contribute to our general
      understanding of nodulation and to the larger question of plant cell signal
      transduction.

PMID- 7737470
TI  - Construction of a food-grade host/vector system for Lactococcus lactis based on
      the lactose operon.
AB  - A plasmid-based food-grade vector system was developed for Lactococcus lactis by
      exploiting the genes for lactose metabolism. L. lactis MG5267 is a plasmid-free
      strain containing the entire lactose operon as a chromosomal insertion. The lacF
      gene was deleted from this strain by a double cross-over homologous recombination
      event. The lacF-deficient strain produced a Lac- phenotype on indicator agar. A
      cloned copy of the lacF gene expressed on a plasmid was capable of complementing
      the lacF-deficient strain resulting in a Lac+ phenotype. This stably maintained
      system fits the requirements of a self-selecting vector system and has the
      potential to be exploited in the food industry.

PMID- 7737471
TI  - Studies on lipopeptide biosynthesis by Bacillus subtilis: isolation and
      characterization of iturin-, surfactin+ mutants.
AB  - Two mutant strains, M35 and M89, were obtained by UV irradiation from a wild-type
      Bacillus subtilis producing iturin and surfactin. Sporulation and surfactin
      production were similar in both mutants and in the parent strain, while the
      iturin production of M35 was 300-fold less than that of the wild-type strain; M89
      did not produce any iturin. The analysis of the incorporation of sodium [1
      14C]acetate into cellular lipids and lipopeptides showed that M89 still
      synthesized beta-amino fatty acids, the lipid moiety of iturin.

PMID- 7737472
TI  - Detection of heat-stable enterotoxin genes among Australian Vibrio cholerae O1
      strains.
AB  - DNA probes derived from the heat-stable enterotoxin gene of Vibrio cholerae non
      O1 (stn), and the cholera toxin gene (ctx), were used to screen 199 strains of V.
      cholerae O1, which were isolated within Australia from 1977-1986. 13
      environmental strains isolated from the riverine environment in Southeast
      Queensland in 1980 and 1981, hybridized with the stn and ctx DNA probes. The
      concentrated supernatant of 6 of these strains elicited fluid accumulation in the
      infant mouse assay both before and after heating at 100 degrees C for 5 min.
      Genetic relationships among the 13 stn+ strains were studied by a comparison of
      the rRNA-RFLPs (ribotyping) and by Southern blot analysis with a stn gene probe.
      The results indicate that there is a clonal relationship among the Australian
      stn+ strains and that there is an environmental reservoir of stn genes among
      Australian V. cholerae O1 isolates.

PMID- 7737473
TI  - A cytochrome P450-like gene possibly involved in oleandomycin biosynthesis by
      Streptomyces antibioticus.
AB  - A cosmid clone from an oleandomycin producer, Streptomyces antibioticus, contains
      a large open reading frame encoding a type I polyketide synthase subunit and an
      oleandomycin resistance gene (oleB). Sequencing of a 1.4-kb DNA fragment adjacent
      to oleB revealed the existence of an open reading frame (oleP) encoding a protein
      similar to several cytochrome P450 monooxygenases from different sources,
      including the products of the eryF and eryK genes from Saccharopolyspora
      erythraea that participate in erythromycin biosynthesis. The oleP gene was
      expressed in Escherichia coli as a fusion protein to a maltose-binding protein.
      Using polyclonal antibodies against this fusion protein it was observed that the
      synthesis of the cytochrome P450 was in parallel to that of oleandomycin. The
      cytochrome P450 encoded by the oleP gene could be responsible for the epoxidation
      of carbon 8 of the oleandomycin lactone ring.

PMID- 7737474
TI  - Cloning, sequencing and production of the lantibiotic mersacidin.
AB  - Mersacidin is a lanthionine-containing peptide antibiotic that shows a good in
      vivo efficiency against methicillin-resistant Staphylococcus aureus. It is
      excreted during early stationary phase and could be purified from culture
      supernatant in a one-step procedure by reversed phase HPLC. Its structural gene
      was cloned from chromosomal DNA of the producer strain Bacillus subtilis HIL Y
      85,54728. Sequencing revealed that pre-mersacidin consists of an unusually long
      48 amino acid leader sequence and a 20 amino acid propeptide part which is
      modified during biosynthesis to the mature lantibiotic. The comparison of the
      mersacidin prepeptide with those of hitherto known lantibiotics demonstrates that
      mersacidin is more closely related to type B lantibiotic cinnamycin than to type
      A lantibiotics.

PMID- 7737475
TI  - Characterization of eukaryotic-like kinase activity in Escherichia coli using the
      gene-protein database.
AB  - The gene-protein database was used to obtain the two-dimensional polyacrylamide
      gel coordinates of proteins phosphorylated in extracts of Escherichia coli
      including those phosphorylated by eukaryotic-like kinase activities. These
      suggest that the phosphoproteins correspond to, or co-migrate with, the product
      of an open reading frame at 1.3 min (Orf80), Enzyme 1 of the phosphoenolpyruvate
      dependent phosphotransferase system (PtsI), the tRNA synthetase for histidine
      (HisS), and proteins involved in the response to carbon starvation and quinone
      treatment.

PMID- 7737476
TI  - Enhanced formation of isoamyl alcohol in Zygosaccharomyces rouxii due to
      elimination of feedback inhibition of alpha-isopropylmalate synthase.
AB  - Mutants of the 'miso' yeast, Zygosaccharomyces rouxii, that produced a large
      amount of isoamyl alcohol, an important flavour in miso fermentation, were
      isolated from 5,5,5-trifluoro-DL-leucine-resistant mutants, an analogue of L
      leucine. One of the mutants, M21-10, produced a three-fold higher level of
      isoamyl alcohol than the wild-type strain MY21 in miso fermentation. The activity
      of alpha-isopropylamalate synthase, one of the enzymes used for L-leucine
      synthesis, in the mutant M21-10 was not inhibited by the addition of L-leucine, a
      feedback inhibitor.

PMID- 7737477
TI  - Iron uptake in Pseudomonas aeruginosa mediated by N-(2,3-dihydroxybenzoyl)-L
      serine and 2,3-dihydroxybenzoic acid.
AB  - Pseudomonas aeruginosa is known to have an inducible uptake system for the
      enterobacterial siderophore enterobactin. In this work we have examined iron
      transport mediated by the biosynthetic precursor 2,3-dihydroxybenzoic acid and N
      (2,3-dihydroxybenzoyl)-L-serine, a breakdown product of enterobactin. Iron
      complexed with 2,3-dihydroxybenzoyl-L-serine was transported into P. aeruginosa
      IA1 via a transport system which is energy-dependent and iron-repressible. The
      rate of transport was not altered by growing the cells in the presence of either
      pyoverdin or pyochelin, which have been shown previously to induce transport via
      that system. Growth of the cells in the presence of enterobactin did cause an
      increase in the rate of transport, indicating that the complex can be transported
      by the inducible enterobactin uptake system, but also that a separate system must
      exist. In contrast, transport of iron complexed with 2,3-dihydroxybenzoic acid
      was neither iron-repressible nor strongly energy-dependent, from which we
      conclude that there must be a novel mode of transport not characteristic of iron
      siderophore transport systems.

PMID- 7737478
TI  - Comparison of type IV-pilin genes of Pseudomonas aeruginosa of various habitats
      has uncovered a novel unusual sequence.

PMID- 7737479
TI  - Production of Escherichia coli LamB protein in Yersinia enterocolitica.
AB  - Plasmid pBCP 68 carrying the lamB gene of Escherichia coli was introduced and
      expressed in Yersinia enterocolitica cells. The presence of LamB protein in the
      outer membrane of the wild-type strain of Y. enterocolitica coincided with the
      loss of the OmpC and OmpF porins. Western blot analysis showed that LamB in Y.
      enterocolitica cells co-migrated with authentic monomeric LamB, indicating that
      its signal peptide was recognized and cleaved by Y. enterocolitica and properly
      integrated into the outer membrane. The expression of LamB made Y. enterocolitica
      sensitive to phage lambda.

PMID- 7737480
TI  - Adenosine kinase-deficient mutant of Saccharomyces cerevisiae.
AB  - A cordycepin-resistant mutant strain of Saccharomyces cerevisiae (CD-R2) was
      found to be deficient in adenosine kinase. This mutant accumulated S
      adenosylhomocysteine during growth in the presence of exogenous adenosine and it
      grew in a pseudohyphal manner in the presence of this nucleotide.

PMID- 7737481
TI  - Defective sterol delta 5(6) desaturase as a cause of azole resistance in Ustilago
      maydis.
AB  - Resistance to azole antifungals in Ustilago maydis was associated with a leaky
      defect in sterol delta 5(6)desaturase. This defect resulted in reduced
      accumulation of 14 alpha-methylergosta-24(28)-diene-3 beta,6 alpha-diol and an
      increase in the proportion of 14 alpha-methylfecosterol in treated cells when
      compared to the parent strain. The results demonstrate the importance of this
      mechanism in pathogenic fungi.

PMID- 7737482
TI  - Use of conjugative and thermosensitive cloning vectors for transposon delivery to
      Mycobacterium smegmatis.
AB  - Conjugative, thermosensitive shuttle plasmids capable of transfer from
      Escherichia coli to Mycobacterium smegmatis were constructed. They contain both
      an E. coli replicon and a thermosensitive derivative of the pAL5000 mycobacterial
      replicon. Using a temperature shift protocol, the conjugative plasmid, pJAZ11 was
      used to deliver the transposon Tn611 from E. coli into the chromosome of M.
      smegmatis. Analysis of transconjugants revealed the random insertion of the
      transposon.

PMID- 7737483
TI  - Chromosomal polymorphism of MEL genes in some populations of Saccharomyces
      cerevisiae.
AB  - Using pulsed-field gel electrophoresis of chromosomal DNA and hybridization with
      the MEL1 probe, we determined the chromosomal locations of polymeric alpha
      galactosidase genes in monosporic cultures of natural strains of Saccharomyces
      cerevisiae. An unusual phenomenon consisting of an accumulation of the MEL genes
      has been found in some specific Saccharomyces cerevisiae populations. Many
      strains possessed a new MEL gene located on chromosome I.

PMID- 7737484
TI  - Degradation of trichlorophenols by Alcaligenes eutrophus JMP134.
AB  - The degradation of chlorophenols by Alcaligenes eutrophus JMP134 (pJP4) was
      studied. The strain grew on 2,4,6-trichlorophenol or 2,4,6-tribromophenol as the
      sole carbon and energy source. Complete degradation of 2,4,6-trichlorophenol was
      confirmed by chloride release and gas chromatography analysis of supernatants
      from growth cultures. The 2,3,5-, 2,3,4-, 2,3,6- and 2,4,5-isomers of
      trichlorophenol did not support growth. However, up to 40% of 2,4,5
      trichlorophenol was mineralized during growth of A. eutrophus on chemostats fed
      with either phenol (0.4 mM) or 2,4,6-trichlorophenol (0.4 mM) plus 2,4,5
      trichlorophenol (0.1 mM). Growth on 2,4,6-trihalophenols was also observed in A.
      eutrophus JMP222, the strain lacking pJP4, suggesting that this new degradative
      ability reported for A. eutrophus is not related to pJP4 encoded catabolic
      functions.

PMID- 7737485
TI  - Expression of the genes for insecticidal crystal proteins in Bacillus
      thuringiensis: cryIVA, not cryIVB, is transcribed by RNA polymerase containing
      sigma H and that containing sigma E.
AB  - To investigate the mechanism of transcriptional regulation of cryIVA and cryIVB,
      encoding 130-kDa dipteran-active crystal proteins, in Bacillus thuringiensis
      subsp. israelensis, we introduced each gene into several sporulation mutants of
      Bacillus subtilis. A spoIIG mutation, the wild-type gene of which encodes sigma E
      precursor, completely blocked the cryIVB transcription. In contrast, low but
      detectable transcription of cryIVA was observed in the spoIIG mutant. In the wild
      type B. subtilis, no transcription of cryIVB was detected before T2 (2 h after
      the onset of stationary phase), while the cryIVA transcription started at the
      late exponential phase at low levels. Furthermore, in a wild-type strain of B.
      thuringiensis subsp. israelensis, transcription of cryIVA began earlier than that
      of genes encoding other crystal components, cryIVB and cytA. A consensus sequence
      recognized by an RNA polymerase containing sigma H of B. subtilis was found
      upstream of the transcription start point of cryIVA, which overlapped with that
      recognized by sigma E.

PMID- 7737488
TI  - Will improving detection of depression in primary care lead to improved
      depressive outcomes?

PMID- 7737486
TI  - Activation of the actinorhodin biosynthetic pathway in Streptomyces lividans.
AB  - Production of the antibiotic actinorhodin was activated in Streptomyces lividans
      under conditions in which it is not normally produced when transformed with an
      activator gene from S. lividans. The gene encodes a 86-nucleotide transcript,
      responsible for the actinorhodin production phenotype, which is homologous to the
      132 nucleotide transcript from S. fradiae, thought to act as a putative antisense
      RNA.

PMID- 7737487
TI  - Identification of Azospirillum strains by restriction fragment length
      polymorphism of the 16S rDNA and of the histidine operon.
AB  - DNA fingerprints of several Azospirillum strains, belonging to the five known
      species A. amazonense, A. brasilense, A. halopraeferens, A. irakense and A.
      lipoferum, were obtained by restriction analysis of the amplified 16S rDNA and by
      restriction fragment length polymorphism of the histidine biosynthetic genes.
      Data obtained showed that amplified rDNA restriction analysis is an easy, fast,
      reproducible and reliable tool for identification of Azospirillum strains, mainly
      at the species level, whereas restriction fragment length polymorphism could, in
      some cases, differentiate strains belonging to the same species. Moreover, both
      analyses gave congruent results in grouping strains and in the assignment of new
      strains to a given species.

PMID- 7737490
TI  - Psychiatric morbidity among frequent attender patients in primary care.
AB  - In this study, 96 frequent attender patients in primary care were compared with
      466 other primary care patients. The focus was on psychiatric morbidity, current
      and former psychiatric treatment, and self-perceived need for treatment. The
      prevalence of psychiatric illness was much greater among frequent attender
      patients than other patients (54.0% vs. 24.0%, p < 0.001), and subclinical
      symptoms were common in both groups (34.0% vs. 43.2%). Depression and anxiety
      were the most common clinical entities among frequent attender patients. However,
      very few patients had psychiatric treatment and the self-perceived need for
      treatment was low. The significance of these findings is discussed in the paper.

PMID- 7737489
TI  - A model curriculum for mental disorders and behavioral problems in primary care.
AB  - Changes in the health care delivery system will increasingly emphasize the role
      of the primary care physician in diagnosing and treating mental disorders and
      behavioral problems. This increasing emphasis points to the need for more
      systematic definition of the knowledge and skills that future primary care
      physicians will need for effective delivery of mental health services. The model
      curriculum described in this paper represents the efforts of a multidisciplinary
      Task Force to describe basic training objectives for the psychiatric education of
      future primary care physicians.

PMID- 7737491
TI  - Evolution and evaluation of a medical psychiatric unit.
AB  - In 1991, the first Medical Psychiatric Unit (MPU) in Australia was established at
      the Royal Prince Alfred Hospital, Sydney. The processes involved in introducing
      it to the hospital staff and administration, as well as its structure and
      criteria for admission, are described. Its development was compared to the
      experiences of others in North America over the past 15 years. The functioning of
      the MPU over the subsequent 2 years was evaluated by assessing demographic and
      clinical criteria of patients admitted. Data were obtained from patient medical
      records and compared with similar data on patients admitted to a General
      Psychiatric Unit (GPU). It was found that patients of the MPU tended to be older,
      more often male, and suffering from organic brain syndromes and/or alcohol or
      drug abuse. Despite the multiplicity of diagnoses and the complexity of treatment
      procedures, the MPU patients' duration of stay was similar to the GPU patients'.
      The MPU was found to have achieved goals of clinical and cost-effectiveness. It
      has become an established subunit within the Department of Psychiatry.

PMID- 7737492
TI  - Nondetection of depression by primary care physicians reconsidered.
AB  - This article examines the rates of detection for major depression and other
      depressive disorders by family physicians as well as the differences between
      detected and undetected cases in terms of a variety of demographic and clinical
      variables. A total of 1,580 family practice patients completed a screening form
      and were rated by their physician. Patients with elevated Center for
      Epidemiologic Studies-Depression Scale (CES-D) scores were oversampled for
      possible interviews using the Structure Clinical Interview for DSM-III-R (SCID).
      In the resulting weighted sample, family physicians detected 34.9% of cases of
      major depression and 27.9% of cases of any depressive disorder. Detection was
      associated with pharmacological and psychological intervention. However, the
      undetected cases tended to be mildly depressed and higher functioning. Presence
      of a current anxiety disorder facilitated detection. Overall, the mildness of
      undetected depression and associated impairment have implications for estimates
      of the consequences of primary care physicians' low rates of nondetection and for
      the development of interventional strategies to improve their performance.

PMID- 7737493
TI  - Psychiatric problems of pediatric end-stage renal failure.
AB  - Our study compared 53 children with end-stage renal disease (26 children on
      continuous ambulatory peritoneal dialysis and 27 children with kidney
      transplants) to a matched sample of 27 healthy children. Seventeen of the
      children on dialysis (65.4%) exhibited separation anxiety disorder, which was
      associated with the family psychological environment. After receiving kidney
      transplantation, school maladjustment continued, and adjustment disorder was seen
      in eight children (29.6%). The adjustment disorder was related to poor
      relationships with peers at school.

PMID- 7737494
TI  - Testosterone replacement therapy in HIV illness.
AB  - The purpose of this study was to determine whether testosterone replacement
      therapy ameliorates sexual dysfunction and associated problems of mood, energy,
      and appetite in HIV+ men with immune suppression (CD4 < 400 cells/cu mm) and low
      levels of serum testosterone. Assessments at study baseline and endpoint included
      psychiatric evaluation using the Structured Clinical Interview for DSM-III-R, the
      Hamilton Rating Scale for Depression, Clinical Global Impressions Scale, the
      Karnofsky Performance Index, and a side-effects rating scale. Eighty-one men
      entered treatment and 72 completed at least 8 weeks. At study entry, 84% had an
      AIDS-defining condition (1993 CDC Criteria). In terms of sexual interest and
      function, 85% of study completers were clearcut responders at week 8. Mood
      response was also good: of the 44 study completers who had mood problems at
      baseline, 28 (64%) were rated as much improved. Mean change in CD4 cell count
      after treatment was not statistically significant. These findings suggest that
      testosterone replacement therapy should be considered for men with immune
      suppression and low testosterone levels who complain of diminished sexual desire
      and/or dysfunction. Replication with a placebo component is indicated.

PMID- 7737495
TI  - Irritable bowel syndrome and family history of psychiatric disorder: a
      preliminary study.
AB  - A series of 70 consecutive patients with irritable bowel syndrome (IBS) were
      interviewed concerning their family history of psychiatric disorders. A series of
      60 consecutive patients with major depression (MDE) were also interviewed, as
      were a control group of 46 relatives of patients with organic brain disease. The
      results showed that both IBS and MDE groups had a similar, higher prevalence of
      relatives with psychiatric illness than controls, and that this was due to a
      higher prevalence of anxiety and depressive disorder in the relatives. The
      implications of these findings are discussed.

PMID- 7737496
TI  - The role of ciprofloxacin in a patient with delirium due to multiple etiologies.
AB  - A 40-year-old female with a lumbar drain was admitted to the neurosurgery service
      with a bacterial meningitis. During the course of her treatment with multiple
      central nervous system (CNS) active medications, the patient became disoriented
      and agitated with visual hallucinations and generalized myoclonus. A psychiatric
      consultation was requested. The case is presented and discussed within the
      context of the importance of understanding etiological mechanisms in treating and
      reversing delirium. The fluoroquinolone agent ciprofloxacin was considered to be
      the primary etiology of the patient's delirium. This class of medication as a
      cause of altered mental status is discussed.

PMID- 7737497
TI  - Cotard's syndrome in psychogeriatric patients in Hong Kong.
AB  - Cotard's syndrome is characterized by the presence of nihilistic delusions. A
      retrospective case note study of 349 Chinese psychogeriatric patients in Hong
      Kong showed a prevalence of 0.57% of the syndrome. The two patients identified
      were both females with major depression. Case vignettes of these patients were
      presented and the similarity of the clinical features to those described in the
      Western literature was discussed.

PMID- 7737498
TI  - Occurrence of high levels of posttraumatic stress disorder symptoms in patients
      who had survived a myocardial infarction or coronary artery bypass graft surgery.

PMID- 7737499
TI  - Pseudoseizures.

PMID- 7737500
TI  - Cloning and heterologous expression of the genes encoding nonspecific electron
      transport components for a cytochrome P450 system of Saccharopolyspora erythraea
      involved in erythromycin production.
AB  - The forA gene encoding a protein that can function as a NADH:ferredoxin
      oxidoreductase (For) has been cloned from Saccharopolyspora erythraea, the
      erythromycin A (ErA) producer. In a previous study For protein, together with the
      FdxA ferredoxin from the same organism, was shown to be able to reconstitute the
      cytochrome P450 system responsible for the hydroxylation of 6-deoxyerythronolide
      B, an intermediate of ErA biosynthesis. Nucleotide sequence data suggest that the
      cloned forA gene codes for For, the putative pyruvate dehydrogenase component,
      dihydrolipoamide dehydrogenase, or its close homolog. Overexpression of forA
      appeared to be toxic to Escherichia coli.

PMID- 7737501
TI  - The 16S-23S rRNA intergenic spacer region of Bartonella (Rochalimaea) species is
      longer than usually described in other bacteria.
AB  - We amplified by polymerase chain reaction (PCR) and sequenced using an automated
      laser fluorescent DNA sequencer (Pharmacia) the intergenic spacer region (ITS)
      between the 16S and 23S rRNAs of the four species of Rochalimaea which were
      recently renamed Bartonella sp. We obtained DNA fragments of 1211, 1262, 1258 and
      1529 bp for the reference species of B. quintana, B. henselae, B. vinsonii and B.
      elizabethae, respectively. The ITS of the four species are longer than previously
      reported in prokaryotes and contained the genes encoding isoleucine-tRNA
      (tRNA(Ile)) and alanine-tRNA (tRNA(Ala)). The sequences of the tRNA(Ala) genes
      are identical for the four Bartonella species, but the tRNA(Ile) gene sequence of
      B. quintana presents one mutation in comparison with the other species.

PMID- 7737502
TI  - The evolutionary relationship of biphenyl dioxygenase from gram-positive
      Rhodococcus globerulus P6 to multicomponent dioxygenases from gram-negative
      bacteria.
AB  - The Gram+ bacterium Rhodococcus globerulus P6 (RgP6) catabolizes a range of
      polychlorinated biphenyl (PCB) congeners, thus being of interest in
      bioelimination processes for PCB. The first step in the pathway, a dioxygenase
      attack of one of the biphenyl (BP) rings, is catalyzed by biphenyl dioxygenase
      (BDO). In this study, the nucleotide (nt) sequences of the four clustered
      cistrons, bphA1A2A3A4, encoding the subunits of BDO and forming part of the bph
      operon of RgP6 for BP degradation, were determined. A conserved motif proposed to
      bind a Rieske-type [2Fe-2S] cluster was identified in the deduced amino acid (aa)
      sequence of both the a subunit of the terminal oxygenase (BphA1) and ferredoxin
      (BphA3). The ferredoxin reductase subunit (BphA4) contains conserved sites for
      FAD and NADH binding. Deduced aa sequences of the BDO subunits shared homologies
      to multicomponent aromatic ring-hydroxylating dioxygenases from Gram-
      microorganisms. Stronger identity was found to toluene dioxygenase (TDO) of
      Pseudomonas putida F1 than to other BDO. Aa sequence comparisons suggest that BP
      degradation genes of RgP6 may have originated in Gram- microorganisms, probably
      Pseudomonas, and subsequently transferred to this Gram+ bacterium.

PMID- 7737503
TI  - Toxic phospholipases D of Corynebacterium pseudotuberculosis, C. ulcerans and
      Arcanobacterium haemolyticum: cloning and sequence homology.
AB  - The genes encoding toxic phospholipases D (PLD) from Corynebacterium
      pseudotuberculosis (Cp)biovar equi and C. ulcerans (Cu) have been cloned and
      sequenced. The deduced proteins are 307 amino acids (aa) in length and include a
      putative signal sequences of 26-aa. A molecular mass of 31.2 and 31.0 kDa and pI
      values of 8.84 and 6.73 are predicted for the secreted (mature) proteins from Cp
      and Cu, respectively. Comparison of the deduced primary structure of the two
      proteins to those of the PLD produced by Cp biovar ovis and Arcanobacterium
      haemolyticum (Ah) revealed that the four enzymes share 64-97% identity. The aa
      sequences of this group of proteins were unique when compared to the sequences of
      other phospholipases in GenBank and were found to share only small regions of
      homology with other proteins, including two conserved domains of glyceraldehyde-3
      phosphate dehydrogenase (G3PD). The similarity of PLD from Cp biovar equi, Cu and
      Ah to the PLD of Cp biovar ovis suggests that these enzymes may act as virulence
      determinants.

PMID- 7737505
TI  - Isolation, characterization and overexpression of the yeast gene, GLR1, encoding
      glutathione reductase.
AB  - Using degenerate oligodeoxyribonucleotides based on the N-terminal amino acid
      (aa) sequence of a yeast glutathione reductase (GR) CNBr-generated peptide
      fragment and a conserved C-terminal region of known GR aa sequences, the yeast
      gene encoding GR, GLR1, was isolated using PCR followed by screening of a yeast
      genomic DNA plasmid library. GLR1 encodes a 467-aa protein with a deduced M(r) of
      51,545. Comparison with Escherichia coli and human GR sequences reveals 49.8% aa
      identity. Yeast cells transformed with a multicopy plasmid containing the genomic
      clone overproduced GR activity sixfold. GLR1 was found not to be an essential
      gene.

PMID- 7737504
TI  - Yeast vectors for the controlled expression of heterologous proteins in different
      genetic backgrounds.
AB  - An expression system for Saccharomyces cerevisiae (Sc) has been developed which,
      depending on the chosen vector, allows the constitutive expression of proteins at
      different levels over a range of three orders of magnitude and in different
      genetic backgrounds. The expression system is comprised of cassettes composed of
      a weak CYC1 promoter, the ADH promoter or the stronger TEF and GPD promoters,
      flanked by a cloning array and the CYC1 terminator. The multiple cloning array
      based on pBIISK (Stratagene) provides six to nine unique restriction sites, which
      facilitates the cloning of genes and allows for the directed cloning of cDNAs by
      the widely used ZAP system (Stratagene). Expression cassettes were placed into
      both the centromeric and 2 mu plasmids of the pRS series [Sikorski and Hieter,
      Genetics 122 (1989) 19-27; Christianson et al., Gene 110 (1992) 119-122]
      containing HIS3, TRP1, LEU2 or URA3 markers. The 32 expression vectors created by
      this strategy provide a powerful tool for the convenient cloning and the
      controlled expression of genes or cDNAs in nearly every genetic background of the
      currently used Sc strains.

PMID- 7737506
TI  - The presence of tRNA pseudogenes in mammalia and plants and their absence in
      yeast may account for different specificities of pre-tRNA processing enzymes.
AB  - Six of 13 cloned members of the human tRNA(Val) gene family code for tRNA(Val)
      pseudogenes, of which all but one are transcribed efficiently in HeLa cell
      extracts. Due to single or multiple mismatches in stem regions, the corresponding
      pre-tRNAs are resistant against the action of human 5'- and 3'-processing enzymes
      and are thus prevented from being converted to mature tRNAs. Surprisingly, all of
      them are accurately and efficiently processed to mature-sized tRNA in yeast
      nuclear extract. This is in agreement with corresponding studies of plant pre
      tRNAs which are not processed in wheat germ extract but are rapidly processed in
      yeast extract. These observations imply that the yeast pre-tRNA 5'- and 3'
      maturases do not monitor the three-dimensional structure of their substrates as
      stringently as mammalian and plant enzymes, possibly because tRNA pseudogenes do
      not occur in yeast.

PMID- 7737508
TI  - The U6 snRNA-encoding gene of the monogenetic trypanosomatid Leptomonas
      collosoma.
AB  - The U6 snRNA (U6) is the most conserved small nuclear RNA (snRNA) and apparently
      plays a central role in catalysis of the cis-splicing reaction. In trans
      splicing, U6 may have an additional function. In the nematode trans-splicing
      system, a direct interaction between the U6 and spliced leader (SL) RNAs has been
      demonstrated, suggesting that U6 may serve as a bridge between the SL RNA and the
      acceptor pre-mRNA. To examine possible phylogenetic conservation of
      trypanosomatid U6 sequences that may interact with spliceosomal RNAs, we have
      cloned and sequenced the U6 gene from the monogenetic trypanosomatid Leptomonas
      collosoma (Lc). The Lc U6 deviates from the Trypanosoma brucei (Tb) RNA only in
      four positions located in the 5' stem-loop and the central domains. As in Tb, U6
      is a single-copy gene and two tRNA genes, tRNAGln and tRNAIle, are found upstream
      to the gene. The tRNAs are differentially expressed; tRNAGln is transcribed in
      the opposite direction to U6, whereas tRNAIle is not transcribed. Possible base
      pairing between U6 and the U2 and SL RNAs, similar to the interactions that take
      place in the nematode trans-splicing system, are proposed.

PMID- 7737507
TI  - Analysis and expression of the Candida albicans FAS2 gene.
AB  - Candida albicans (Ca) FAS2, the gene encoding the alpha-subunit of fatty acid
      synthase (FAS), has been isolated and characterized. Saccharomyces cerevisiae
      (Sc) FAS2 was used as a probe to screen genomic libraries of Ca, strain 4918.
      Clones were obtained that contained all but the first 1 kb of the gene. The 5'
      end, as well as upstream sequences, were subsequently isolated by PCR. The Ca
      FAS2 gene is comprised of an open reading frame (ORF) of 5655 bp that is free of
      introns and encodes a 207, 587-Da protein of 1885 amino acids. The Ca FAS2 gene
      and the encoded polypeptide exhibit 70 and 67% homology with the Sc FAS2 gene and
      protein, respectively. The gene specifies a single transcript of approx. 6 kb,
      and transcript levels are regulated independently of morphogenesis. Chromosome
      analysis localized the gene to chromosome 3. In addition, no differences were
      noted when comparing the FAS2 sequence, that encompasses the cerulenin-binding
      domain of FAS, between strain 4918 and two derived cerulenin-resistant (CerR)
      mutants. Thus, alteration within this region is not responsible for the increased
      CerR of the mutant strains.

PMID- 7737509
TI  - The gene encoding streptothricin acetyltransferase (sat) as a selectable marker
      for Leishmania expression vectors.
AB  - The pLEX series of vectors was developed for the stable expression of exogenous
      genes in the protozoan parasite Leishmania. These pUC-based constructs contain
      one of three independent selectable markers and a multiple cloning site inserted
      between the upstream and downstream untranslated regions of the previously cloned
      Leishmania major HEXBP gene. Selection was based on resistance to the
      aminoglycosides, hygromycin B and neomycin, and to nourseothricin, a novel
      independent selectable marker for transfection of Leishmania. The vectors were
      introduced into Leishmania promastigotes by electroporation and were maintained
      as extrachromosomal circular concatemers containing between four and eight repeat
      units of the pLEX monomer. To demonstrate the efficient expression of cloned
      exogenous genes using the pLEX system, promastigotes were transfected with a pLEX
      construct that contained a second drug-resistant selectable marker gene cloned
      into the expression site, and clones were obtained that grew on media containing
      two antibiotics. These vectors, together with the novel selectable marker, will
      further facilitate the molecular analysis of gene expression in Leishmania.

PMID- 7737510
TI  - A new vector-host system for construction of lacZ transcriptional fusions where
      only low-level gene expression is desirable.
AB  - We improved a multicopy vector, pRS415 [Simons et al., Gene 53 (1987) 85-96], for
      use in operon fusion constructions by introducing a new multiple cloning site
      (MCS) containing eight unique restriction sites upstream from the promoterless
      reporter gene lacZ. In order to reduce plasmid copy number, a new Escherichia
      coli strain SP2 (pcnB, delta lac, recA) was constructed. This strain permits
      analysis of fusions in cases where high gene dosage may be detrimental.

PMID- 7737511
TI  - Cloning and inducible synthesis of poliovirus non-structural proteins in
      Saccharomyces cerevisiae.
AB  - Several coding regions of the poliovirus (PV) genome were cloned in the yeast
      Saccharomyces cerevisiae, and placed under the control of the inducible hybrid
      promoter pGAL/CYC, such that expression was triggered by incubating the cells in
      galactose (Gal)-containing medium. A number of PV genes encoding non-structural
      proteins, including 2Apro, 2B, 2C, 3A, 3AB and 3Cpro, were cloned and expressed
      in this eukaryotic system. The presence of these proteins after induction was
      detected by immunoblot analysis using specific antisera against each protein. The
      levels and the kinetics of protein synthesis after induction varied according to
      the PV protein analyzed. Thus, 2C was detected soon after Gal addition (3-5 h)
      and was one of the major polypeptides synthesized by yeast cells after 16 h of
      induction. In contrast, only low levels of synthesis were observed for 3A or 3AB,
      and then only after several hours of growth in Gal. The induction of the PV
      protease, 2Apro, was highly toxic for the cells such that growth was arrested
      after 5 h of induction and cell survival sharply declined.

PMID- 7737512
TI  - Characterization of phage that bind plastic from phage-displayed random peptide
      libraries.
AB  - During routine screenings of random peptide libraries displayed at the N terminus
      of the pIII coat protein of M13 bacteriophage, clones were isolated that bound
      directly to the polystyrene (PS) surface used to immobilize the target protein.
      The plastic-binding phage (P-b phi) bind to both unblocked plastic (PS and
      polyvinyl chloride, PVC) and plastic blocked with bovine serum albumin (BSA) but
      require non-ionic detergent to bind to plastic blocked with milk. Comparison of
      the P-b phi to antibody-binding phage (Ab-b phi) indicates that similar numbers
      of phage particles are bound, but fewer P-b phi the recovered by acid elution.
      Sequence determination of the displayed peptides reveals they lack amino-acid
      sequence similarity yet are highly enriched for the Tyr and Trp residues.
      However, because not all phage that display peptides rich in Tyr and Trp residues
      bind to plastic, and other methods of screening random peptide libraries have
      identified different classes of plastic-binding peptides, the relative abundance
      of Tyr and Trp residues should not be considered diagnostic of plastic-binding.
      In summary, these results help characterize one of the most common methods used
      to screen random peptide libraries and suggest strategies to avoid isolating P-b
      phi. Furthermore, while it is generally believed that proteins bind to plastic by
      non-specific interactions, these results show that a bias in aa composition can
      exist.

PMID- 7737513
TI  - Regulation of sCD4-183 gene expression from phage-T7-based vectors in Escherichia
      coli.
AB  - In this paper, we describe various parameters affecting the regulation of
      expression of the sCD4-183 gene, encoding the 183-amino-acid soluble human two
      domain CD4 protein, from phage-T7-based pET vectors. We demonstrated that for the
      sCD4-183 protein, the highest protein yield was obtained using vector pET-9a, in
      which neither expression of the T7 RNA polymerase-encoding gene nor the target
      gene was tightly regulated. The highest overall protein yield was obtained from
      cells grown for 24 h in the absence of inducer, a strategy that may be generally
      useful for production of less toxic proteins. We also describe two modifications
      of the pET vector system that effectively minimized leaky (uninduced) expression
      and enhanced plasmid stability. These have potential use in the production of
      toxic proteins, or of non-toxic proteins produced in high-density cultures.

PMID- 7737514
TI  - IS1222: analysis and distribution of a new insertion sequence in Enterobacter
      agglomerans 339.
AB  - With a length of 1221 bp and 44-bp inverted repeats with ten mismatches, IS1222
      was identified as an endogenous insertion sequence in Enterobacter agglomerans
      339. In this host strain, four copies were located, three on the nif plasmid pEA9
      and one at the chromosome. Sequence analysis showed two consecutive open reading
      frames, orfA and orfB, encoding putative polypeptides of 87 and 276 amino acids.
      In-between both reading frames, a potential frameshift window of the
      homonucleotide type was postulated, followed by a pseudoknot structure and a
      ribosome-binding site. Based on significant homology at the sequence level and
      similarity of the features discussed, IS1222 was placed among the group of IS3
      elements with IS407, IS476 and ISR1 being the most closely related IS.
      Hybridization experiments suggest that the distribution of IS1222 is limited to a
      group of related bacterial strains among Enterobacteriaceae.

PMID- 7737516
TI  - Cloning and characterization of a gene cluster, phsBCDEF, necessary for the
      production of hydrogen sulfide from thiosulfate by Salmonella typhimurium.
AB  - We cloned, by complementation of an H2S- mutant, a cluster of Salmonella
      typhimurium genes, phsBCDEF, that appears to be essential for the anaerobic
      production of hydrogen sulfide from thiosulfate. Tn5 mutagenesis and ExoIII
      deletion analysis showed that approx. the entire region of a 3.3-kb subclone was
      necessary for H2S production. Subsequent sequencing revealed the presence of five
      potential translationally coupled open reading frames (ORFs). Their putative
      protein products were confirmed by synthesis from a phage T7 expression system.
      Comparison of the encoded sequences with previously determined sequences suggests
      that these genes constitute part of a thiosulfate-reducing operon coding for a
      membrane-associated electron transport chain which contains proteins potentially
      capable of ligating iron-sulfur clusters and heme. Immediately upstream from
      these genes, a region encoding the C-terminal portion of an ORF (OrfA) was
      identified that showed a high degree of similarity to some other anaerobic
      terminal reductases, polysulfide reductase (PsrA) of Wolinella succinogenes and
      dimethylsulfoxide reductase (DmsA), formate dehydrogenase (formate-hydrogene
      lyase linked) (FdhF) and nitrate reductase (NarG) of Escherichia coli.

PMID- 7737517
TI  - Isolation and characterization of the Vibrio cholerae acfA gene, required for
      efficient intestinal colonization.
AB  - The nucleotide sequence of the Vibrio cholerae acfA gene (encoding an accessory
      colonization factor) has been determined. Sequence analysis revealed the presence
      of an open reading frame of 215 amino acids with a characteristic signal
      peptidase I (SPI) cleavage site at the N terminus. Electrophoretic analysis of
      proteins synthesized by Escherichia coli cells, following T7 promoter/RNA
      polymerase-directed expression of acfA, revealed a 23-kDa protein corresponding
      to the mature form of AcfA. The T7 expression system also showed that, in the
      presence of known SPI inhibitors, a 25-kDa unprocessed form of AcfA is produced.

PMID- 7737519
TI  - Sequence of the bphD gene encoding 2-hydroxy-6-oxo-(phenyl/chlorophenyl)hexa-2,4
      dienoic acid (HOP/cPDA) hydrolase involved in the biphenyl/polychlorinated
      biphenyl degradation pathway in Comamonas testosteroni: evidence suggesting
      involvement of Ser112 in catalytic activity.
AB  - The nucleotide sequence of bphD, encoding 2-hydroxy-6-oxo
      (phenyl/chlorophenyl)hexa-2,4-dienoic acid hydrolase involved in the
      biphenyl/polychlorinated biphenyl degradation pathway of Comamonas testosteroni
      strain B-356, was determined. Comparison of the deduced amino-acid sequence with
      published sequences led to the identification of a 'lipase box', containing a
      consensus pentapeptide sequence GlyXaaSerXaaGly. This suggested that the
      mechanism of action of this enzyme may involve an Asp-Ser-His catalytic triad
      similar to that of classical lipases and serine hydrolases. Further biochemical
      and genetic evidence for the active-site involvement of Ser112 was obtained by
      showing that a semipurified enzyme was inhibited by PMSF, a classic inhibitor of
      serine hydrolases, and by site-directed Ser112-->Ala mutagenesis.

PMID- 7737518
TI  - Genetic linkage in Pseudomonas aeruginosa of algT and nadB: mutation in nadB does
      not affect NAD biosynthesis or alginate production.
AB  - The 68-min region of the chromosome of Pseudomonas aeruginosa (Pa) contains the
      gene algT, encoding a putative alternate sigma factor similar to sigma E in
      Escherichia coli, that is required for the expression of several genes in the
      alginate biosynthetic regulon. Sequences immediately upstream from algT were
      found to contain a divergently expressed open reading frame encoding a 60-kDa
      protein with 64 and 36% identity to the nadB gene products of E. coli and
      Bacillus subtilis, respectively. The nadB gene encodes L-aspartate oxidase and
      has been shown in several bacteria to be essential for de novo nicotinamide
      adenine dinucleotide (NAD) biosynthesis. Pa nadB complemented the growth
      requirement for nicotinic acid in a nadB mutant strain of E. coli, suggesting
      that this gene encodes a functional homologue of L-aspartate oxidase. A
      nadB::Tn501 mutant was constructed by gene replacement in the alginate-producing
      strain, Pa FRD. This NadB- mutant still produced alginate and appeared normal
      with respect to the regulation of alginate synthesis. Interestingly, the NadB-
      mutant did not have an auxotrophic phenotype for nicotinic acid, indicating that
      this nadB was not essential for NAD biosynthesis in Pa. These results suggest the
      possibility that Pa has an alternate mechanism for de novo NAD biosynthesis.

PMID- 7737515
TI  - Sequence of the hpcC and hpcG genes of the meta-fission homoprotocatechuic acid
      pathway of Escherichia coli C: nearly 40% amino-acid identity with the analogous
      enzymes of the catechol pathway.
AB  - The meta-fission pathway for homoprotocatechuic acid (HPC) catabolism is
      chemically analogous to the oxidative meta-fission pathway for catechol
      degradation and so provides an opportunity to investigate how the enzymes of
      chemically similar, but specific, pathways might have arisen. Two more genes of
      the HPC pathway from Escherichia coli C, hpcC, encoding 5-carboxymethyl-2
      hydroxymuconic acid semialdehyde (CHMS) dehydrogenase, and hpcG, encoding 2
      oxohept-3-ene-1,7-dioic acid (OHED) hydratase, have now been sequenced to aid
      this analysis. The CHMS dehydrogenase showed 40% amino acid (aa) sequence
      identity with the corresponding enzyme of the catechol pathway, and the OHED
      hydratase showed 36% aa sequence identity with the catechol pathway hydratase.
      The CHMS dehydrogenase is a member of the aldehyde dehydrogenase superfamily that
      includes enzymes from animal, plant and microbial sources. Since it appears that
      the dioxygenase, isomerase and decarboxylase enzymes of the two pathways are not
      closely related, it is proposed that the two sets of enzymes have arisen
      separately, but with the muconic acid semialdehyde dehydrogenases and the
      hydratases being recruited, respectively, from the same ancestral sources.

PMID- 7737520
TI  - An enhanced broad-host-range vector for gram-negative bacteria: avoiding
      tetracycline phototoxicity during the growth of photosynthetic bacteria.
AB  - A mobilizable, broad-host-range (bhr) plasmid was derived from the widely used
      IncP1 vector pRK415. The new vector, pRKD418, contains an additional resistance
      gene and an enlarged multiple cloning site (MCS) region. The optimal growth of
      pRK415-containing bacteria under photosynthetic conditions generally requires the
      use of optical filters to protect the selective antibiotic tetracycline (Tc) from
      photooxidation with the resulting production of toxic photoproducts; pRK415 is
      not stably maintained in the absence of selective pressure. The addition of a
      trimethoprim-resistant dihydrofolate reductase-encoding gene provided for optimal
      photosynthetic growth in the presence of a selective antibiotic without any
      special apparatus. The presence of an antibiotic marker not found in commonly
      used cloning vectors in many cases facilitates the subcloning of inserts into the
      bhr plasmid. The new MCS region provides further cloning flexibility with at
      least sixteen available restriction sites. Easily constructed derivative
      plasmids, exemplified by pRKD418KmE, provide a convenient screening procedure for
      the detection of recombinants during subcloning.

PMID- 7737522
TI  - Cloning and sequencing of the gene coding for dextranase from Streptococcus
      salivarius.
AB  - We cloned and sequenced the dextranase (Dex) (1,6-alpha-glucanhydrolase; EC
      3.2.1.11)-encoding gene from Streptococcus salivarius (Ss) strain M-33.
      Recombinant clones from an Ss genomic library specifying Dex activity were
      identified as colonies surrounded by transparent halos on blue dextran plates.
      One of the clones had a 4.3-kb KpnI fragment containing the gene coding for an
      826-amino-acid polypeptide with a molecular mass of 87.9 kDa, which corresponds
      well to that of native Dex from the Ss culture supernatant. There was no sequence
      homology between the gene encoding Ss Dex and the gene encoding dextran
      glucosidase of S. mutans, or between their protein products.

PMID- 7737521
TI  - Molecular cloning of the gene encoding RecF, a DNA repair enzyme, from
      Streptococcus pyogenes.
AB  - RecF is a component of one of the bacterial DNA repair systems. The start codon
      of the recF gene of Streptococcus pyogenes resides about 4.4 kb downstream from
      the end of hasA, the hyaluronan synthase-encoding gene, which is transcribed in
      the opposite orientation. The deduced 368-amino-acid RecF protein is 43.5%
      identical to its homolog from Bacillus subtilis. When cloned on a plasmid, recF
      could complement a S. pyogenes deletion mutant that was sensitive to ultraviolet
      irradiation and chemical mutagens. This is the first report of a recF sequence
      from a Gram+ pathogen.

PMID- 7737523
TI  - The sequencing of the 80-kDa D15 protective surface antigen of Haemophilus
      influenzae.
AB  - The 80-kDa D15 antigen (D-15-Ag) has previously been shown to be a target for
      protective immunity and conserved amongst typeable and nontypeable Haemophilus
      influenzae. Here, the gene encoding D-15-Ag is shown to encode a 797-aa
      polypeptide which, after cleavage of the predicted signal peptide, would have a
      molecular mass of 85,632 Da.

PMID- 7737524
TI  - Red, scaly spot with a central horn.

PMID- 7737525
TI  - Resistant hypertension: what to do after trying 'the usual'.
AB  - Hypertension is considered to be "resistant" if a patient's diastolic blood
      pressure remains above 90 mm Hg despite the use of full doses of three
      antihypertensive medications. The most likely causes of ineffective blood
      pressure control include inadequate drug regimens and patient factors such as
      noncompliance, obesity, cigarette smoking, alcoholism, and "office hypertension."
      The two most common physiologic causes of resistance are volume overload and
      secondary hypertension, particularly renovascular disease. When suspicion of
      renovascular hypertension is high, immediate renal arteriography is indicated. In
      most patients, however, the less invasive captopril challenge is an adequate
      screening test. Most hypertensive patients with true resistance can be treated by
      altering their medication regimen.

PMID- 7737526
TI  - Older women's health: 'taking the pulse' reveals gender gap in medical care.
AB  - In the United States, for every 100 men age 65 and older, there are 147 women, a
      ratio that has social and medical consequences. Five panelists "take the pulse"
      of older women's health in general and in the offices of primary care physicians
      in particular. They assess the status of medical education and the need to
      include older women in research and drug trials, issues of gender bias in health
      insurance and quality of treatment, ways to improve the use of preventive health
      services--such as mammography and Pap smears--by older women, and the role of
      office physicians in identifying and helping victims of domestic violence.

PMID- 7737527
TI  - Alzheimer's disease: how to give and monitor tacrine therapy.
AB  - Up to one-third of patients with mild to moderate Alzheimer's disease may show
      improvement in cognitive function with tacrine, a centrally-acting,
      noncompetitive inhibitor of acetylcholinesterase. Candidates for tacrine must
      have a diagnosis of probable Alzheimer's dementia based on NINCDS-ADRDA or DSM-IV
      criteria and should have no history of liver disease. For patients receiving the
      drug, do follow-up cognitive testing with a sensitive measure such as the
      Alzheimer's Disease Assessment Scale. The most common adverse effects associated
      with tacrine therapy are elevated liver transaminases and gastrointestinal
      effects. Weekly blood tests are necessary to monitor liver function. A reliable
      caregiver is essential to ensure compliance with frequent dosing and weekly blood
      testing.

PMID- 7737528
TI  - Taking the pulse of older women's health. Despite advances, gender gap still
      exists in medical education, research, and clinical care.

PMID- 7737529
TI  - Effects of aging and chronic hypertension on cerebral blood flow and
      cerebrovascular CO2 reactivity in the rat.
AB  - We measured regional cerebral blood flow (rCBF) in young and old Wistar-Kyoto
      (WKY) and spontaneously hypertensive (SHR) rats by a minimally invasive
      microsphere technique. Blood flows to the cerebrum, diencephalon, mesencephalon,
      cerebellum and pons-medulla during normocapnia were determined. To test the
      ability of the vessels to dilate, rCBF was also measured during hypercapnia.
      Reactivity to CO2 was calculated as delta rCBF/delta paCO2. In the old SHR, blood
      flow to the pons-medulla (88 +/- 8 ml/min/100 g, mean +/- SEM) was markedly lower
      than that in the young SHR (107 +/- 4 ml/min/100 g, p < 0.05), whereas the
      difference of those values in the old and young WKY rats was slight (0.05 < p <
      0.1). There were no differences in the values of blood flow to the cerebrum,
      diencephalon, mesencephalon or cerebellum between the young and old rats in both
      species. Cerebrovascular CO2 reactivity was markedly impaired in the old SHR (p <
      0.05) compared to that in the young SHR, but the difference in reactivity in the
      WKY rats was not significant. The results indicate that blood flow to the pons
      medulla is reduced in association with age, particularly in the hypertensive
      animals, and that the ability of the cerebral vessels to dilate is impaired
      homogeneously by the combination of chronic hypertension and aging.

PMID- 7737530
TI  - Nerve cell loss in the myenteric plexus of the human esophagus in relation to
      age: a preliminary investigation.
AB  - Morphometric measurements have been carried out on the human myenteric esophageal
      neurons at the ages of 20-40 and more than 70 years. The number of neurons
      decreases after 70 years of age, which is accompanied by an increase in the sizes
      of the neurons. In percentage terms the decrease in the number of neurons in the
      aged varied from 22 to 62% along the esophagus being most pronounced in its
      superior third at the junction with the pharynx.

PMID- 7737531
TI  - Body measurements of black and white elderly persons with emphasis on body
      composition.
AB  - The measurements obtained on 103 male and female subjects, 60-103 years of age,
      who were participants in a community nutrition program, included weight, height,
      knee height, body mass index, triceps skinfold, midarm circumference, midarm
      muscle area, total body fat, total body water, and lean body mass. Over the 43
      year range of this cross-sectional study, 78% of body weight loss in men and 51%
      in women was attributable to lean tissue, while fat tissue accounted for 22% of
      weight loss in men and 53% in women. Analysis of variance of the measured values
      over the age interval showed trends that were not statistically significant among
      males, but females showed significant decreases in weight, body mass index,
      triceps skinfold, midarm muscle area, total body fat (% and lb), total body water
      (l), and lean body mass; also, a significant increase in total body water (%) was
      observed in females. Ethnic differences among the parameters included higher
      triceps skinfold in white than in black males and larger knee height and midarm
      circumference in white than in black females. Comparison of parameters by gender
      within each ethnic group showed larger body weight and midarm muscle area in
      white males than in white females; triceps skinfold was larger in black females
      than in black males. t tests indicated that subjects who received home-delivered
      meals had significantly smaller mean body weight, body mass index, triceps
      skinfold, midarm circumference and total body fat (% and lb) than those who came
      to a senior center for the noon meal. Elderly who lived alone had a higher total
      body fat (%) than those who lived with other(s). In females, significant
      correlation coefficients (r) were shown by weight, total body water (l), and lean
      body mass with all parameters. The weakest r values in females were those for
      height and for triceps skinfold with other parameters. In males, there was no
      single parameter that correlated with all others; triceps skinfold correlated
      with none. The strongest correlations in the male were for weight with total body
      water and with lean body mass, and for midarm circumference with midarm muscle
      area.

PMID- 7737532
TI  - Humoral response to influenza hemagglutinin: oligoclonal spectrotype and failure
      of thymopentin as immunoadjuvant.
AB  - Influenza remains a serious cause of illness and death among certain populations.
      Influenza vaccines in use at present are of limited effectiveness due to the high
      variability of the virus, and trials all over the world are in progress to
      enhance their immunogenicity. Conflicting results, in fact, have been reported
      about the immune response to influenza vaccination in diverse populations. In
      this paper we analyzed the antibody response to the hemagglutinin (HA) of the
      H3N2 A/Shangai 16/89 strain, which was included into the trivalent 1991-92
      influenza vaccine, in four groups of subjects: 8 healthy young, 13 human
      immunodeficiency virus (HIV)-infected and 37 elderly healthy people, 9 of whom
      were treated with thymopentin (TP-5). Our results show levels of anti-HA IgG
      before vaccination in HIV-infected and elderly people significantly lower than
      those of normal young subjects. After vaccination, HIV-infected and elderly
      healthy people showed a significant increase of specific antibodies, whereas a
      failure in the specific response in normal young subjects was observed, thus
      differences among the groups were no longer present. Moreover, the spectrotypic
      analysis of antibody response, by isoelectric focusing and reverse blotting,
      showed oligoclonal but polymorphic pattern in the majority of subjects,
      irrespective of the group, and more frequently lack of expansion of the
      spectrotype after vaccination, thus demonstrating the lack of the recruitment of
      antigen-specific B cells. Finally, the treatment with TP-5 did not influence the
      outcome of the vaccination in the group of elderly people. These results further
      emphasize the limited immunogenicity of influenza vaccination and the inefficacy
      of TP-5 as immunoadjuvant, in this model of vaccination.

PMID- 7737533
TI  - No differences in the incidences of old people's hip fractures between urban and
      rural populations--a comparative study in two Finnish health care regions in
      1989.
AB  - In a prospective study, incidences of hip fractures among the aged in urban and
      rural populations were compared in two health care regions in Finland in 1989.
      Both the administrative and the more informative functional classification of the
      municipalities were used. During 1989, a total of 366 patients, aged 55 years and
      above, who had a permanent place of domicile in either one of the two health care
      regions, were treated for a fresh hip fracture. In both regions women sustained
      80% of the fractures. No significant differences were found in the incidences of
      hip fractures between the urban and rural populations. However, a significant
      difference was found in the mean incidence between the towns of the two health
      care regions (t = 4.228, d.f. = 6, p < 0.01).

PMID- 7737534
TI  - Tumor necrosis factor, natural killer activity and other measures of immune
      function and inflammation in elderly men with heart failure.
AB  - OBJECTIVE: To determine the status of tumor necrosis factor (TNF) and other
      measures of immunity and inflammation in chronic heart failure (CHF) in the
      elderly. DESIGN: Comparative survey study of subjects with heart failure and age
      matched controls. SETTINGS: University affiliated tertiary care VA Medical
      Center, Heart Failure Clinic. PATIENTS: Twenty men with New York Class II and III
      heart failure and 17 age-matched controls. INTERVENTIONS: None. MAIN OUTCOME
      MEASURE: Levels of lymphocyte mitogenesis, TNF, natural killer (NK) cell
      activity, elastase-alpha 1-antitrypsin (E/alpha) and cross-linked fibrin D-dimers
      (XDP). RESULTS: TNF levels (p = 0.27), NK activity (p = 0.56), and lymphocyte
      mitogenesis (p = 0.67) were similar in patients and controls. E/alpha levels were
      somewhat lower in CHF patients (p = 0.05) and XDP were similar (p = 0.59).
      However, TNF levels were significantly related to NK activity and to E/alpha
      activity in elderly men with heart failure but not controls. XDP were positively
      related to NK in heart failure patients but not controls. CONCLUSION: TNF and
      other measures of immune function and inflammation do not appear to be
      significantly elevated in elderly patients with heart failure of moderate
      severity. However, significant relationships exist between TNF, NK activity, XDP
      and E/alpha in the heart failure patients only, suggesting that immune activation
      and subclinical inflammation does exist in these patients.

PMID- 7737536
TI  - [Significance of the morphologic structure of surface endometrium in rat
      reproduction after microsurgical uterine anastomosis].
AB  - The influence of selected suturing methods of the uterus horn on the reproductive
      ability of rat females, uterus wall morphology and endometrium surface was
      assessed. It was found out that the operative trauma involvement of the mucosa
      resulted in such regressive and degenerative changes as: changes in the
      muscularis continuity, diverticula of uterine cavity, fibrosis, endometrium
      atrophy and mucosa focal oedema of the "cystic micro-polyp" type. The
      morphological changes resulted in reproduction impairment in the animals where
      the surgical suture involved the mucosa of their uteri.

PMID- 7737537
TI  - [Evaluation of qualitative values of blood flow indices in uterine and arcuate
      arteries during the third trimester of normal pregnancy].
AB  - We presented in our study obtained values of qualitative indices of blood flow in
      uteroplacental circulation in the third trimester of normal pregnancy. We
      performed examinations in 154 pregnant women with pregnancy age of 32-42 wk. We
      evaluated blood flow velocity in uterine and arcuate arteries by means of
      qualitative analysis of blood flow waveforms. We proved that in the third
      trimester of normal pregnancy qualitative parameters of blood flow decrease
      slightly what may suggest that there is systematic placental perfusion increase.

PMID- 7737538
TI  - [Fluoride concentration in mother and fetus. I. Placental transport of
      fluorides].
AB  - Authors estimated the relationship between maternal blood fluorides concentration
      and umbilical venous fluorides concentration considering many parameters related
      to the gestation and the labor. It has been discussed the importance of placental
      fluorides transport.

PMID- 7737535
TI  - Cholesterol screening in the elderly: changing attitudes.
AB  - The purpose of this study was to assess an elderly population's (60-80 years old)
      attitudes toward health prevention and life-style change with a particular
      emphasis on cholesterol screening and management. A free cholesterol screen was
      offered to participants in exchange for completion of a 21-item questionnaire
      (including medical history, risk factors, attitudes on preventive health, eating
      patterns and demographic information). This study provides evidence for
      increasing awareness of elevated cholesterol levels as a risk factor for coronary
      heart disease. It also demonstrates that there is an attitude of willingness to
      modify dietary cholesterol and fat intake within this mobile elderly population.

PMID- 7737539
TI  - [Acid-base equilibrium in umbilical blood vessels of fetuses with perinatal
      hypoxemia symptoms].
AB  - The aim of the study was to compare acid-base parameters in umbilical cord blood
      of fetus from groups with hypoxaemia symptoms and from the control group
      (physiological deliveries). 111 fetuses were divided into 8 groups. Group I
      consisted of 33 fetuses with normal heart rate baseline while groups II-VIII
      involved fetuses from complicated labours with hypoxaemia symptoms. The following
      characteristics of umbilical vessels blood: low pH, normal or increased PCO2,
      increased base deficit, low PO2 and PO2 in chronic hypoxaemia were found out.
      Acute hypoxaemia was characterised by lower pH, high PCO2, normal BE and lower
      PO2 and SO2.

PMID- 7737540
TI  - [Endometriosis in clinical materials from the years 1981-1990].
AB  - In the group of 213 women with diagnosed endometriosis, after the histological
      analysis of the samples obtained during surgical procedure the following factors
      have been determined: the character and frequency of complaints, prevalence of
      the disease depending on the age of patients, it's localisation, coexistence with
      the neoplasms of the genital tract, indications for the surgical treatment and
      it's type. Taking into account the difficulties in diagnosing endometriosis, it's
      occurrence in young women and the possibility of malignant transformation along
      with the coexistence with malignant neoplasms of genital tract, we are convinced
      that the surgical intervention should be undertaken in order to achieve the
      better cure rate as well as to improve the accuracy of diagnosis.

PMID- 7737543
TI  - [Synthesis of estradiol by endometrial stroma cells under the influence of
      epidermal growth factor (EGF) in vitro].
AB  - The endometrial samples were obtained from 13 operated women in the proliferative
      phase of menstrual cycle. The tissue culture of endometrial stromal cells was
      established. After the cells were growth to the confluency, EGF was added to
      dishes of study group to the final concentrations of 5 ng/ml. Culture media of
      study and control groups were collected every 48, 96, 144, 192 hours and
      lyophylized. The estradiol level was measured in culture media by RIA. The mean
      estradiol concentrations in culture media of endometrial stromal cells decreased
      during the time of experiment in the control: 318 pg/ml, 276 pg/ml, 186 pg/ml and
      110 pg/ml and study group respectively: 339 pg/ml, 279 pg/ml, 169 pg/ml and 129
      pg/ml. There was no significant influence of EGF (5 ng/ml) on estradiol level in
      culture media in each time intervals.

PMID- 7737541
TI  - [Erosion of the uterine cervix in women with primary infertility treated with CO2
      laser].
AB  - The authors described the results of treatment of erosions of the uterine cervix
      in 78 women with primary sterility with CO2-laser vaporisation in Department of
      Reproduction, Institute of Gynecology and Obstetrics, Academy of Medicine,
      Poznan. The results were estimated through clinical, cytological and
      colposcopical examinations in the term of 6 weeks and 3 months after therapy. The
      Insler's cervical mucus test was done in all women after 3 months. In all women
      the healing was achieved and five of them were needed for second laser therapy
      because of superficial endometriosis. The authors think that CO2-laser
      vaporisation (under colposcopical control) of erosions of the uterine cervix in
      women with primary sterility is the reliable method. The wound's healing after
      laser therapy is quick and without any complications. Laser therapy causes no
      trauma of the cervix structure and does not disturb in excretion of mucus by
      cervical glands.

PMID- 7737542
TI  - [Electro-conization of the uterine cervix in the Department of Oncologic
      Gynecology in Lodz in the years 1968-1987].
AB  - Considering the carcinoma incidence rate in women population the cervical
      carcinoma takes the second place. The diagnosis and proper treatment of the
      precancerous conditions and the preinvasive carcinoma cause the reduction of
      invasive cancer incidence rate. In this paper, it has been presented 20-years
      experience concerning cervical electro-conization in above mentioned department.
      The 1515 patients with the precancerous conditions and the carcinoma
      intraepitheliale were studied. The electro-conization has made possible the
      recovery in 98.0% patients. It has been found that the electro-conization is a
      very valuable diagnostic and therapeutic procedure, does'nt cause any serious
      complications and provide with undamaged samples for histopathological studies.

PMID- 7737544
TI  - [Synthesis and characteristics of anti-CBG antibodies (anti-transcortin)].
AB  - We used corticosteroid binding globulin purified by chromatography on the
      Sepharose column for immunisation of the rabbits. We analysed serum by rocket
      immunoelectrophoresis and cross immunoelectrophoresis. The titre of the serum was
      estimated by reaction with 125 I-labelled transcortin (corticosteroid binding
      globulin). The results of our studies indicate that own serum is valuable and can
      be use for radioimmunoassay of the CBG in the serum.

PMID- 7737545
TI  - [Conservative treatment of breast cancer--indications and surgical technique].
AB  - Comparison of the results of conservative surgery and radiotherapy with
      mastectomy in the treatment of the breast cancer are discussed. The indications,
      contraindications and surgical technique on conservative surgery are presented.

PMID- 7737546
TI  - [Diseases of peripheral vessels during pregnancy and puerperium: diagnosis,
      prevention and treatment].
AB  - Pregnancy and puerperal period are favorable factors for appearance of or
      deterioration of peripheral vessels diseases and simultaneously limits ability of
      treatment. In the case of varicose veins the compressing therapy is the method of
      choice. The appearance of thromboemboli is the indication to the long time
      heparin treatment and according to other authors even to the surgery. In some
      cases implantation of the special filter to the inferior vena cava is necessary
      to prevent the pulmonary embolism. The worst form of thrombosis-phlegmasia
      cerulea dolens is the absolute indication to surgery. Pregnancy at patients with
      previous reconstructions in the aorto-iliac segment needs frequent examination of
      fetus and blood flow in the graft to avoid many dangerous complications. At
      pregnant women with peripheral vessels diseases examination using color
      ultrasonic doppler is method of choice. In some cases pregnancy should be treated
      as a high risk pregnancy and should remain under obstetrician and vascular
      surgeon care.

PMID- 7737547
TI  - [Cleft lip and palate coexisting with a skull and brain defect diagnosed in a
      fetus with ultrasound].
AB  - In a pregnant woman admitted to the hospital due to imminent preterm labour cleft
      and brain complex defect was found by routine us. Acusoon 128 CD unit was
      employed. A technique allowing diagnosis of the bony face malformations was
      presented.

PMID- 7737548
TI  - Psychological factors in gastro-oesophageal reflux disease.

PMID- 7737549
TI  - Acute gastrointestinal haemorrhage in patients treated with anticoagulant drugs.

PMID- 7737551
TI  - Rising death rate from non-malignant disease of the oesophagus (NMOD) in England
      and Wales.
AB  - Between 1968 and 1991, the number of deaths from non-malignant oesophageal
      disease (NMOD) (International Classification of Diseases code 530), recorded by
      the Office of Population Censuses and Surveys (OPCS) in England and Wales,
      trebled in women, from 118 to 340 (5 to 13 per million) and doubled in men, from
      131 to 251 (5.5 to 10 per million). Calculation of age specific death rates,
      shows the increase to result from a rise in mortality in those over 75 years and
      age standardised mortality confirms a rise in overall frequency from 2.9 to 7.0
      deaths per million men and 5.2 to 13.1 per million women. Between 1974 and 1988
      when specific diagnoses were coded, deaths from oesophageal ulcer rose from 1.5
      to 2.5 per million. In men, the death rate from oesophageal stricture increased
      from 2.5 to 3 per million and in women from 3.5 to 6 per million. Mortality from
      oesophageal perforation did not change (1 per million). Some of these changes
      reflect the increasing age of the population in general, but further explanations
      are required. Review of 84 sets of case notes from a total of 281 inpatients
      whose coded diagnoses had included NMOD and who had died suggested that in 28
      (33%) death was actually due to NMOD, and in seven of these endoscopic
      intervention was responsible. The certified underlying cause of death was
      compared with that suggested from case note review in 62 cases; death from NMOD
      was substantially underestimated. This study concludes that a rising death rate
      attributed to NMOD is underestimated on death certificates and that endoscopic
      intervention explains only a few of the cases.

PMID- 7737550
TI  - Role of biliary stenting in the management of bile duct stones in the elderly.

PMID- 7737552
TI  - Omeprazole 10 mg or 20 mg once daily in the prevention of recurrence of reflux
      oesophagitis. Solo Investigator Group.
AB  - This study determined the optimal maintenance dose of omeprazole in reflux
      oesophagitis. One hundred and ninety three patients rendered asymptomatic and
      healed after four or eight weeks omeprazole were randomised double blind to 10 mg
      omeprazole once daily (n = 60 evaluable), 20 mg omeprazole once daily (n = 68),
      or placebo (n = 62) for one year or until symptomatic relapse. Each omeprazole
      regimen was superior to placebo in preventing both symptomatic relapse (life
      table analysis, p < 0.001) and endoscopically verified relapse (p < 0.001). At 12
      months, the life table endoscopic remission rates (proportions of patients
      without grade > or = 2 oesophagitis) were: 50% (95% confidence intervals 34 to
      66%) with 10 mg omeprazole once daily, 74% (62 to 86%) with 20 mg omeprazole once
      daily, and 14% (2 to 26%) with placebo. At 12 months, the life table symptomatic
      remission rates (proportions of patients asymptomatic or with mild symptoms)
      were: 77% (64 to 89%) with 10 mg omeprazole once daily, 83% (73 to 93%) with 20
      mg omeprazole once daily, and 34% (16 to 52%) with placebo. Both 10 mg and 20 mg
      omeprazole once daily were effective in prolonging the remission of reflux
      oesophagitis: 10 mg may be appropriate to start longterm treatment, though the
      existence of a dose response relation means that 20 mg once daily may be
      effective in patients for whom 10 mg once daily is suboptimal.

PMID- 7737553
TI  - Integrity and characteristics of secondary oesophageal peristalsis in patients
      with gastro-oesophageal reflux disease.
AB  - Secondary peristalsis contributes to oesophageal acid clearance. The aim of the
      study was to evaluate the integrity and characteristics of secondary peristalsis
      in patients with gastro-oesophageal reflux disease. Studies were performed in 22
      patients with reflux disease and 20 age matched controls. Oesophageal motility
      was recorded at 3 cm intervals along the oesophageal body. Primary peristalsis
      was tested with 5 ml water swallows. Secondary peristalsis was stimulated with 10
      ml boluses of air and water injected in the mid-oesophagus and by 5 second
      distensions with a 3 cm balloon at the same level. It was found that primary
      peristalsis was normal in 19 of 20 control subjects and in 14 of 22 patients with
      reflux disease. In patients with reflux disease, intact secondary peristalsis was
      triggered infrequently by air and water distension (median success rate of 0% for
      both stimuli) and occurred significantly less frequently than in control subjects
      (50% and 30% respectively). The frequency of balloon induced secondary
      peristalsis, however, was similar in the two groups (0% controls, 20% reflux
      disease). The major pattern of failure of secondary peristalsis was the complete
      absence of any oesophageal secondary peristaltic response. The amplitudes of the
      intact secondary peristaltic responses were not significantly different for the
      two groups. Peristaltic velocity for air and balloon induced secondary
      peristalsis was also similar in control subjects and patients with reflux disease
      whereas water induced secondary peristalsis was slower in the reflux patients. In
      conclusion, patients with reflux disease exhibit a pronounced defect in the
      triggering of secondary peristalsis.

PMID- 7737554
TI  - Precipitating causes of acid reflux episodes in ambulant patients with gastro
      oesophageal reflux disease.
AB  - Previous studies of the mechanisms that precipitate acid reflux episodes have
      used short term hospital based measurements. A 24 hour pH and motility recording
      system, incorporating a sphincter monitoring device, has been developed to study
      naturally occurring acid reflux episodes in control subjects and patient groups
      with different grades of oesophagitis. Lower oesophageal sphincter relaxations
      related to episodes of acid reflux were common in control subjects (67% of
      episodes) but became more difficult to detect as the grade of oesophagitis
      increased (grade 0/1 - 67%, grade 2/3 - 35%, grade 4 - 13%). A variety of events
      that produced recognisable transdiaphragmatic pressure patterns were associated
      with acid reflux episodes. In control subjects 74% of acid reflux episodes were
      precipitated by belching but this mechanism became less evident as the grade of
      oesophagitis increased (grade 0/1 - 43%, grade 2/3 - 40%, grade 4 - 29%).
      Activities that produced a pressure gradient across the diaphragm became
      increasingly important as events precipitating acid reflux as oesophagitis became
      more severe (controls--2%, grade 0/1 - 15%, grade 2/3 - 11%, grade 4 - 22%). This
      study has shown the pressure events surrounding acid reflux in fully ambulant
      patients with gastro-oesophageal reflux disease.

PMID- 7737555
TI  - Misoprostol inhibits gastric mucosal release of endogenous prostaglandin E2 and
      thromboxane B2 in healthy volunteers.
AB  - Prostaglandin analogues of the E-series theoretically offer the ideal antiulcer
      drugs. Peptic ulcer healing with prostaglandin analogues is, however, no better
      than would be predicted from their ability to inhibit gastric acid secretion and
      they are less effective than histamine H2 receptor antagonists in preventing
      ulcer relapse. It could be that prostaglandin analogues inhibit gastric mucosal
      synthesis or release of endogenous eicosanoids, thereby abrogating their own
      effects. This study, therefore, examined how a single therapeutic dose (200
      micrograms) of misoprostol, a synthetic analogue of prostaglandin E1, influences
      gastric mucosal release of endogenous prostaglandin E2 (PGE2), thromboxane B2
      (TXB2), and chemotactic leukotriene B4 (LTB4) during basal conditions and in
      response to gastric luminal acidification (0.1 M HCl; 5 ml/min for 10 minutes).
      Nine healthy volunteers were studied in a single blind, cross over design. In
      each subject misoprostol or placebo was instilled in randomised order into the
      stomach, which was subsequently perfused with isotonic mannitol. Misoprostol
      significantly decreased basal as well as acid stimulated output of PGE2 and TXB2,
      without affecting output of LTB4. These data show that misoprostol inhibits
      gastric mucosal synthesis of prostanoids. Decreased concentrations, or even a
      changed profile, of native eicosanoids modulating the release of inflammatory
      mediators from immune cells might explain why prostaglandin analogues have a
      comparatively poor clinical performance in ulcer healing and prevention.

PMID- 7737556
TI  - Cytophotometric and flow cytometric DNA content of isolated glands in gastric
      neoplasia.
AB  - The gland isolation method was applied to various gastric lesions to measure DNA
      content by cytophotometry and flow cytometry for the first time. By incubating
      and agitating fresh specimens from surgically resected stomachs in calcium
      magnesium free Hanks's balanced salt solution (CMFH) containing EDTA, many
      neoplastic glandular epithelial cells were successfully isolated from the stroma,
      and their characteristic three dimensional features were seen morphologically.
      The DNA content of pure nuclear suspensions of isolated glands was obtained by
      cytophotometry and flow cytometry staining with 4',6-diamino-2-phenylindole
      dihydrochloride (DAPI) and propidium iodide, respectively. Compared with
      histological grading, the frequency of the DNA aneuploidy of cancer with moderate
      or poor differentiation by cytophotometry (75%) was significantly higher than
      that of well differentiated cancer (25%), but the histological typing of gastric
      cancer DNA frequency were not correlated. This method allowed us to detect small
      aneuploid peaks by flow cytometry, which were previously masked by contaminating
      interstitial cells. The frequency of DNA aneuploidy detected by flow cytometry
      (87.5%) was higher than detected by cytophotometry (58.3%). The results of these
      studies shows the feasibility of this technique for analysing the DNA content of
      various lesions of the stomach.

PMID- 7737557
TI  - Accelerated gastric epithelial proliferation.
AB  - Gastric body mucosal proliferation was quantified and localised under conditions
      of increased gastrin drive using a variety of techniques. Rats were given
      omeprazole 400 mumol/kg/day by gavage and after 30 days mean serum gastrin rose
      11-fold (p < 0.001). Total mucosal polyamines rose 220% from 15.9 to 50.9 nmol/mg
      protein (p < 0.001). This was associated with a 238% increase in crypt cell
      production rate from 0.541 to 1.83 crypt cells/h by vincristine metaphase arrest
      (p < 0.02). Using computer aided counting of proliferating cell nuclear antigen
      (PCNA) immunostained nuclei to assess epithelial proliferation in
      hypergastrinaemia rat stomach: mucus neck cell PCNA labelling was increased by
      41% (p < 0.001) and gland cell PCNA labelling was increased by 222% (p < 0.001).
      PCNA/AgNOR (argyrophilic nuclear organiser regions) co-stained sections were used
      to assess proliferative activity in cycling and non-cycling cell populations.
      Data from these experiments suggest that, in addition to increasing the number of
      mucosal cells in cycle, cell life and cell cycle duration may be reduced in
      hypergastrinaemia.

PMID- 7737558
TI  - Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion
      and promotes gastric prostaglandin E2 synthesis in healthy volunteers.
AB  - The selective muscarinic M1 receptor antagonist, pirenzepine, considerably
      stimulates duodenal mucosal bicarbonate secretion in the rat and increases
      gastric luminal release of prostaglandin E2 (PGE2) in humans. This study,
      therefore, looked at the effect of pirenzepine on bicarbonate secretion and
      luminal output of PGE2 into the stomach and the duodenum of nine healthy
      volunteers using a new technique permitting simultaneous measurements. In the
      stomach modified sham feeding increased bicarbonate secretion from 382 (62)
      mumol/h (mean (SEM)) to 959 (224) mumol/h (p < 0.02). In the duodenum modified
      sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb
      increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27)
      mumol/cm x h (p < 0.02) and 634 (157) mumol/cm x h (p < 0.01), respectively.
      Pirenzepine (10 mg/h intravenously) reduced basal and vagally stimulated gastric
      and basal duodenal bicarbonate secretion by about 50% (p < 0.03). In the stomach,
      but not the duodenum, basal and vagally stimulated PGE2 output increased
      significantly (p < 0.05) in response to pirenzepine. In conclusion, human
      gastroduodenal mucosal bicarbonate secretion is regulated by a pirenzepine
      sensitive mechanism, which is probably cholinergic. The rise in gastric PGE2
      output seen in response to M1 receptor inhibition by pirenzepine suggests the
      existence of a feed back loop secondary to the decrease seen in bicarbonate
      secretion.

PMID- 7737559
TI  - A substantial proportion of non-ulcer dyspepsia patients have the same
      abnormality of acid secretion as duodenal ulcer patients.
AB  - Acid secretion in response to gastrin releasing peptide (GRP) is increased six
      fold in Helicobacter pylori positive duodenal ulcer (DU) patients and threefold
      in H pylori positive healthy volunteers, and this fully resolves after
      eradication of the infection. This study was undertaken to determine whether a
      proportion of H pylori positive patients with non-ulcer dyspepsia (NUD) have an
      acid secretion disturbance similar to DU patients. Basal and GRP stimulated
      gastrin concentrations and acid output were examined in 25 H pylori positive NUD
      patients and the results compared with those of 25 H pylori positive healthy
      volunteers, 25 H pylori negative healthy volunteers, and 25 H pylori positive DU
      patients. Compared with the H pylori negative healthy volunteers, GRP stimulated
      gastrin was increased approximately three fold in each of the three infected
      groups. GRP stimulated acid secretion (median, range) was higher in the H pylori
      positive NUD patients (29.6 mmol/h (5.2-46.5)) (p < 0.005) than in the H pylori
      positive healthy volunteers (19.0 (1.0-38.3)) (p < 0.001) or H pylori negative
      healthy volunteers (6.3 (2.8-20.9)) (p < 0.0001). The H pylori positive NUD
      patients, however, had lower acid output than the DU patients (39.1 (17.9-64)) (p
      < 0.005). These findings are consistent with approximately 50% of the NUD
      patients having a similar disturbance of GRP stimulated acid secretion to DU
      patients.

PMID- 7737560
TI  - Effect of Helicobacter pylori status on intragastric pH during treatment with
      omeprazole.
AB  - To test the hypothesis that Helicobacter pylori infection is associated with a
      decreased intragastric acidity during omeprazole therapy, ambulatory 24 hour dual
      point gastric pH recordings were performed in 18 H pylori positive and 14 H
      pylori negative subjects. There was a four to six week washout period between the
      two pH recordings made in each subject after one week courses of placebo or
      omeprazole, 20 mg daily. During placebo, median 24 hour pH values were not
      different in the corpus (H pylori positive = 1.5, negative = 1.4; p = 0.9) or
      antrum (H pylori positive = 1.3, negative = 1.2; p = 0.1). However, during
      omeprazole treatment, median 24 hour pH values were higher in H pylori positive
      subjects, both in the corpus (H pylori positive = 5.5, negative = 4.0; p = 0.001)
      and antrum (H pylori positive = 5.5, negative = 3.5; p = 0.0004). During placebo
      treatment, the only difference between the two groups was a higher later
      nocturnal pH in the antrum in the H pylori positive group. During omeprazole
      treatment, gastric pH was higher both in the corpus and in the antrum in the H
      pylori positive group for all periods, except for mealtime in the corpus. These
      data indicate that omeprazole produces a greater decrease in gastric acidity in
      subjects with H pylori infection than in those who are H pylori negative. It is
      not, however, known whether there is a causal relationship between H pylori
      infection and increased omeprazole efficacy.

PMID- 7737561
TI  - Helicobacter pylori eradication in the African setting, with special reference to
      reinfection and duodenal ulcer recurrence.
AB  - The aim of this study was to determine the effect of Helicobacter pylori
      eradication on the natural history of duodenal ulcer disease, and to determine
      the incidence of reinfection in adult patients where H pylori had been eradicated
      in a community with a high prevalence of the infection. An investigator blinded
      study, with 24 month endoscopic follow up, in subjects where H pylori had been
      eradicated, and similarly treated subjects where it had not been eradicated was
      conducted at a tertiary referral hospital. The patients consisted of a volunteer
      sample of 48 patients with endoscopically proved active duodenal ulcer disease.
      Duodenal ulcers were healed with omeprazole, 20 mg/day. After endoscopically
      confirmed healing, patients were treated with either one (17 patients) or two
      weeks (31 patients) of 'triple therapy'. H pylori status (urease reaction,
      histological tests, and culture of antral biopsy specimens) was determined at
      entry, four weeks after the finish of triple therapy and six, 12, and 24 months
      after this, or whenever an endoscopically proved recurrent duodenal ulcer was
      found. The main outcome measures were the recurrence of duodenal ulceration, over
      24 months in the eradicated and non-eradicated groups and the incidence of
      reinfection by H pylori in the eradicated group during this follow up period.
      Five patients in the eradicated group experienced a duodenal ulcer relapse, of
      which only three were unexplained (1 = reinfected, 1 = gastrinoma). Fifteen of 21
      patients in the non-eradicated group relapsed over the same period (p < 0.001).
      Only two of 27 patients in the eradicated group were reinfected during the 24
      month follow up period. It is concluded that H pylori eradication is an effective
      treatment strategy for the longterm treatment of duodenal ulcer disease, even in
      the high prevalence, African setting. Reinfection is uncommon.

PMID- 7737562
TI  - Effect of gliadin and other food peptides on expression of MHC class II molecules
      by HT-29 cells.
AB  - Expression of major histocompatibility (MHC) class II molecules by enterocytes is
      known to be enhanced in coeliac disease and other disorders characterised by
      intestinal inflammation--an effect thought to be mediated via intestinal
      lymphocytes. To investigate if food peptides can exert direct effects on class II
      expression, the influence of gliadins, casein, and beta lactoglobulin on an
      intestinal epithelial cell line (HT-29) was examined in the absence of immune
      cells. Class II expression was determined by flow cytometry and
      immunofluorescence microscopy using antibodies against the beta chain of all
      products of the gene subregions DR, DQ, and DP. MHC expression was low in HT-29
      cells but could be stimulated by interferon gamma. Tryptin digested gliadin had
      no effect on class II expression. In the presence of interferon gamma, however,
      it was able to amplify MHC class II expression to mean (SEM) 150 (4)%. Casein
      exerted a similar effect (160 (14)%), but undigested gliadin, tryptin digested
      casein, and beta lactoglobulin had no influence. The observations suggest that
      within the concert of cytokine mediated interactions between enterocytes and
      lymphocytes, some dietary peptides could upregulate the presentation of food
      antigens, leading to a more efficient stimulation of lymphocytes, which in the
      case of coeliac disease might result in damage to the enterocytes.

PMID- 7737564
TI  - Effect of gonadectomy on epidermal growth factor values in the gastrointestinal
      tract of male and female CD-1 mice.
AB  - The effects of gonadectomy on the epidermal growth factor (EGF) concentrations in
      the gastrointestinal tract of CD-1 mice were studied. The EGF concentrations in
      the gastrointestinal tissues were always higher in males than in females.
      Gonadectomy led to a decrease in the EGF concentration in males, and an increase
      in females. Gonadectomy with sialoadenectomy led to a decrease in the EGF
      concentrations in the gastrointestinal tract of both sexes; the most significant
      effect being observed in the stomach. Orchidectomy led to a decrease in total
      body weight, and to a significant decrease in the weight and the protein
      concentration (ng.g-1 wet weight of tissue) of the submandibular gland, but had
      no significant effect on the other tissues of the gastrointestinal tract of male
      mice. Body, tissue weights, and protein concentrations did not change with
      oophorectomy. This study shows that male and female gonads have a profound effect
      on the EGF content of the tissues of the gastrointestinal tract and suggests that
      the submandibular gland also influences the EGF concentration in gastrointestinal
      tissues in mice.

PMID- 7737563
TI  - Role of 5-hydroxytryptamine in intestinal water and electrolyte movement during
      gut anaphylaxis.
AB  - Exposure of sensitised intestine to specific allergen is known to produce
      appreciable reduction in water and electrolyte absorption. The mediators
      participating in this process have not been fully characterised. The effects of
      the 5-hydroxytryptamine2 (5-HT2) and 5-HT3 receptor antagonists, ketanserin and
      granisetron, respectively, on water movement during intestinal anaphylaxis were
      studied. Hooded Lister rats (120-150 g) were sensitised to ovalbumen and 14 days
      later, intestinal water and electrolyte movement was assessed at 10 minute
      intervals by in situ jejunal perfusion with a plasma electrolyte solution (PES)
      or PES containing 20 mg/l ovalbumen. Within 20 minutes of exposure to
      PES+ovalbumen, net water secretion that could be completely prevented by the mast
      cell stabilising agent doxantrazole occurred compared with absorption with PES
      alone (median -20 microliters/min/g (interquartile range -43 to -5), n = 11), v
      (107 (86 to 113), n = 10; p < 0.01). Pre-treatment with subcutaneous ketanserin
      200 micrograms/kg (n = 7) or granisetron 300 micrograms/kg (n = 8) partially
      inhibited the secretory response to PES+ovalbumen (18 (11 to 48) and 13 (6 to 32)
      respectively; both p < 0.01 compared with PES+ovalbumen control). After 40
      minutes perfusion with PES+ovalbumen, the changes in water movement were less
      pronounced 24 (-3 to 43) and neither ketanserin or granisetron had any effect
      (ketanserin: 48 (28 to 87), granisetron: 41 (32 to 83); NS). In all experiments,
      sodium and chloride movement paralleled that of water. Thus, the profound water
      secretion that occurs in the early stages of intestinal anaphylaxis is partly 5
      HT dependent because it can be reversed by 5-HT2 and 5-HT3 receptor antagonists.
      Other mediators must also be involved, especially in the late phase of
      anaphylaxis.

PMID- 7737565
TI  - Persistent measles virus infection of the intestine: confirmation by immunogold
      electron microscopy.
AB  - This study sought to investigate persistent measles virus infection of the
      intestine: a novel protocol for immunogold electron microscopy was developed
      using a polyclonal anti-measles nucleoprotein antibody on reprocessed, formalin
      fixed paraffin wax embedded tissue sections. Antibody binding was detected using
      both immunoperoxidase and light microscopy on tissue sections, and 10 nm gold
      conjugated secondary antibody and electron microscopy on ultrathin sections. The
      techniques were validated using both measles infected vero cells and human
      tissues with established measles infection: these included brain affected by
      subacute sclerosing panencephalitis and acute measles appendicitis. The technique
      was applied subsequently to six untreated cases of granulomatous Crohn's disease,
      and two cases of ileocaecal tuberculosis, a granulomatous control. Mumps primary
      antibody--applied to both mumps infected vero cells, and measles infected vero
      cells and tissues studied by immunoperoxidase, and measles antibody on mumps
      infected cells studied by immunoperoxidase and immunogold--were used as
      specificity controls: the primary antibodies identified their respective target
      antigen and there was no antibody cross reactivity. Measles virus nucleocapsids
      labelled with gold conjugated antibody in both infected cells and tissues,
      including foci of granulomatous inflammation in five of six cases of Crohn's
      disease: in the fifth case, the granuloma could not be identified in ultrathin
      section. In one of the tuberculosis cases, a low level of signal was noted while
      the second case was negative. Labelling adopted a characteristic pattern in all
      infected tissues, strengthening the specificity of these findings. This study
      provides the first direct confirmation of persistent measles virus infection of
      the intestine.

PMID- 7737567
TI  - Efficacy and safety of hydrostatic balloon dilatation of ileocolonic Crohn's
      strictures: a prospective longterm analysis.
AB  - Preliminary reports have suggested that dilatation using hydrostatic through the
      scope balloons may be useful for the treatment of Crohn's strictures, A
      prospective longterm follow up (mean (SD) 33.6 (11.2) months) was carried out in
      55 Crohn's patients with 59 ileocolonic strictures submitted to 78 dilatation
      procedures. Hydrostatic balloons were used (Rigiflator, Microvasive) with a
      diameter of 18 mm on inflation. As soon as the balloons became available
      dilatation up to a diameter of 20 and 25 mm was attempted. The dilatations were
      performed under general anaesthesia using propofol (Diprivan). The patients were
      kept for one night in the hospital after dilatation. Seventy (90%) procedures
      were technically successful and passage of the stricture with a 13.6 mm diameter
      colonoscope was possible after 73% of the dilatations. Complications occurred in
      six patients (11%; 8% of procedures), including sealed perforations (n = 2),
      retroperitoneal perforations (n = 2), and intraperitoneal perforations (n = 2).
      Two of the patients were treated surgically with a one stage resection of the
      stricture and recovered uneventfully. Four patients were treated conservatively
      with intravenous fluids and antibiotics. There was no mortality. Dilatation
      completely relieved obstructive symptoms in 20 patients after one procedure, in
      another 14 patients after two (n = 13) or three (n = 1) dilatations. Total
      longterm success rate was 34 of 55 patients (62%). Nineteen patients (38%) were
      operated on because of persistent obstructive symptoms. The data show that
      endoscopic dilatation using the through the scope hydrostatic balloon system
      relieves obstructive symptoms resulting from ileocolonic Crohn's strictures. The
      procedure, however, carries a definite risk of perforation.

PMID- 7737566
TI  - Increased faecal mucin sulphatase activity in ulcerative colitis: a potential
      target for treatment.
AB  - Colonic mucin is heavily sulphated and it has been shown that enzymatic
      desulphation by faecal bacterial sulphatases greatly increases its susceptibility
      to degradation by faecal glycosidases. A possible role for faecal mucin
      sulphatase in the pathogenesis of inflammatory bowel disease has therefore been
      explored. Faecal mucin sulphatase activity assayed using 35S mucin as substrate
      was increased in ulcerative colitis (median 80.2 units/g pellet weight (range 6.9
      1063; 95% confidence intervals (CI): 45.2 to 293.8, n = 22) compared with 11.3
      units/g (range 3.0-53.5; 95% CI: 8.7 to 29.8, n = 17) in healthy controls (p <
      0.01), where one unit released 1000 dpm free sulphate/hour from 35S mucin (1680
      dpm/microgram). Patients with active ulcerative colitis had higher sulphatase
      activity (median 146; 95% CI: 98 to 253 units/g, n = 10) than those with inactive
      ulcerative colitis (median 42.2; CI: 22.5 to 81.6 units/g, n = 12) (p < 0.05).
      Longitudinal studies in patients with ulcerative colitis show fluctuations of
      faecal mucin sulphatase activity corresponding to clinical disease activity in
      six of seven patients. Faecal mucin sulphatase activity was not significantly
      increased in Crohn's disease (median 36.6, range 5.7-106.6; 95% CI: 22.9 to 65.3
      units/g, n = 14). The bismuth salts, bismuth subcitrate and bismuth subsalicylate
      were found to inhibit faecal mucin sulphatase activity at concentrations
      achievable therapeutically. The increased faecal mucin sulphatase activity in
      ulcerative colitis could be the result of greater intraluminal substrate (mucin)
      availability leading to bacterial enzyme induction, but would probably result in
      more rapid degradation of secreted mucin and represents a potential target for
      treatment.

PMID- 7737568
TI  - Hereditary proctalgia fugax and constipation: report of a second family.
AB  - A second family with hereditary proctalgia fugax and internal anal sphincter
      hypertrophy associated with constipation is described. Anorectal ultrasonography,
      manometry, and sensory tests were conducted in two symptomatic and one
      asymptomatic subjects within the same family and further clinical information was
      obtained from other family members. The inheritance would correspond to an
      autosomal dominant condition with incomplete penetration, presenting after the
      second decade of life. Physiological studies showed deep, ultraslow waves and an
      absence of internal anal sphincter relaxation on rectal distension in the two
      most severely affected family members, suggesting the possibility of a
      neuropathic origin. Both of these patients had an abnormally high blood pressure.
      After treatment with a sustained release formulation of the calcium antagonist,
      nifedipine, their blood pressure returned to normal, anal tone was reduced, and
      the frequency and intensity of anal pain was suppressed. These together improved
      the quality of the patients' sleep, which had previously been very troubled
      because of night time attacks of anal pain.

PMID- 7737569
TI  - Scintigraphic measurement of ileocaecal transit in irritable bowel syndrome and
      chronic idiopathic constipation.
AB  - This study investigated the hypothesis that some features of functional
      gastrointestinal disorders may be associated with abnormalities of ileocaecal
      transit by measuring ileocaecal transit using a scintigraphic technique in 43
      patients with chronic constipation, 20 patients with irritable bowel syndrome
      (IBS), and 18 control subjects. Subjects ingested enteric coated capsules, which
      delivered 111-indium radionuclide to the distal ileum. Gammacamera images were
      acquired at hourly intervals until caecal filling was complete. Ileocaecal
      transit was defined as the time between peak scintigraphic activity in the
      terminal ileum and peak activity in the caecum. The mean (SD) ileocaecal transit
      of 103 (50) minutes in patients with IBS was significantly faster than that in
      control subjects (mean (SD) ileocaecal transit 174 (78) minutes, p < 0.002).
      There were no significant differences in ileocaecal transit between patients with
      chronic idiopathic constipation and the control subjects, or between patients
      with constipation predominant and diarrhoea predominant IBS. This study developed
      a practical scintigraphic method of measuring ileocaecal transit. The rapid
      ileocaecal transit in both the constipation and diarrhoea predominant forms of
      IBS suggests that bloating may not after all result from delayed ileal emptying.

PMID- 7737570
TI  - Colorectal cancer screening in asymptomatic populations.
AB  - Colorectal cancer is the second commonest cause of cancer death in the UK. An
      effective national screening programme is urgently required to reduce the
      substantial morbidity and mortality from the disease. The success of any
      screening programme will depend on the screening test detecting early Dukes's A
      carcinomas and adenomatous polyps. Prognosis is directly related to tumour
      staging and a proportion of carcinomas are thought to arise from polyps. Two
      screening methods exist--faecal occult blood testing and sigmoidoscopy. Large
      trials of faecal occult blood testing show that it detects more early lesions
      than in patients presenting with symptoms, but whether this reduces mortality is
      not yet confirmed and lack of sensitivity for cancers and polyps may ultimately
      limits its usefulness. The role of sigmoidoscopy in screening, particularly
      flexible sigmoidoscopy, has not been fully investigated. Flexible sigmoidoscopy
      has a greater sensitivity for distal lesions than stool testing and a randomised
      controlled trial of its efficacy is planned in Britain. Compliance with screening
      is essential to ensure its cost effectiveness in both health and economic terms.
      Large trials of faecal occult blood testing conducted over several years achieved
      compliance rates in excess of 60%, although in smaller studies these are often
      much less. Women frequently participate more than men. There are many reasons for
      non-compliance including lack of appreciation of the concept of asymptomatic
      illness and fear of the screening tests and cancer itself. Colorectal cancer
      screening is relatively cheap compared with breast and cervical cancer screening.
      Provisional cost estimates suggest that the amount spent to detect or prevent
      cancer by screening is similar to the amount required to treat a symptomatic
      patient.

PMID- 7737571
TI  - Serum intercellular adhesion molecule-1 levels in chronic hepatitis C:
      association with disease activity and response to interferon alpha.
AB  - Soluble intercellular adhesion molecule-1 (sICAM-1) is probably released from a
      variety of cells, including leukocytes and endothelial cells at sites of
      inflammation or in the circulation, and serum levels may therefore be used to
      give an indication of immune activation and inflammatory processes. In the
      present study, an ELISA was used to measure serum ICAM-1 levels in 43 patients
      with chronic hepatitis C and these were correlated with histological changes in
      the liver and the response to interferon alpha treatment. Serum ICAM-1 levels
      were significantly higher in patients with chronic hepatitis C infection than in
      normal subjects and correlated positively with the grade of histological
      activity, in particular the degree of portal, periportal, and lobular
      inflammation, but not with the presence of lymphoid aggregates. There was also a
      weak but significant positive correlation between sICAM-1 and serum aspartate
      aminotransferase activities, and sICAM-1 levels were substantially greater in
      patients with than those without cirrhosis. Serum ICAM-1 levels fell
      significantly in 11 responders out of 19 patients treated with interferon alpha,
      whereas levels remained unchanged in the non-responder group. sICAM-1 levels
      correlate with the clinical status of patients with chronic hepatitis C infection
      and fall with successful interferon treatment.

PMID- 7737573
TI  - Prevalence and pattern of familial disease in primary biliary cirrhosis.
AB  - Susceptibility to primary biliary cirrhosis (PBC) may be partly inherited
      although instances of PBC within families are only infrequently described. The
      records of 736 patients with PBC seen over a 25 year period were examined to
      identify those with a positive family history. Ten patients originating from
      eight families were identified, giving a frequency of 1.33%. They comprised
      mother and daughter pairs; in two families both mother and daughter had been seen
      at our clinic. The daughters presented at an earlier age, median 36 years (range
      24-54), than the mothers, 52 years (50-81). During follow up one daughter (45
      years) and six mothers have died (range 53-81 years) and two mothers and one
      daughter have had a transplant aged 57, 57, and 30 years respectively. It is
      concluded that familial PBC is not rare, that it is related to maternally
      inherited factors, and that disease tends to present earlier in the second
      generation.

PMID- 7737572
TI  - Octreotide, the reticuloendothelial system, and experimental liver tumour.
AB  - The inhibitory effect of octreotide on the growth of liver tumour is probably
      mediated (at least in part) by stimulation of the hepatic reticuloendothelial
      system (RES) activity. This study therefore investigated the effect of octreotide
      on the hepatic and splenic RES (assessed by the uptake of technetium 99m labelled
      albumin colloid, 99mTc-AC) in normal and tumour bearing rats and in animals
      treated with gadolinium chloride. The effects of gadolinium chloride and
      octreotide alone or in combination on the growth of liver tumour were also
      studied. Octreotide significantly stimulates both hepatic and splenic uptake of
      99mTc-AC in normal rats and tumour bearing rats. In controls, the uptake of 99mTc
      AC was significantly reduced by gadolinium chloride and was not changed by
      octreotide. RES blockade with gadolinium chloride significantly increased (p <
      0.001) tumour growth compared with controls (hepatic replacement 42%; 95%
      confidence intervals (CI), 27.6 to 56.4 v 16.7%, 95% CI, 11.1 to 21.3%) whereas
      octreotide significantly inhibited (p < 0.001) the percentage hepatic replacement
      by tumour (0.7%; 95% CI, 0 to 2.3 v 16.7%; 95% CI, 11.1 to 21.3). This study
      highlights the importance of the RES in the development of liver tumour.
      Furthermore, octreotide inhibited the growth of liver tumour in rats with RES
      blockade, albeit to a lesser degree than in normal animals. These findings
      suggest that octreotide inhibits the growth of hepatic tumour by mechanisms other
      than stimulation of RES activity.

PMID- 7737574
TI  - Purification and assay of secretory lithostathine in human pancreatic juice by
      fast protein liquid chromatography.
AB  - Impaired secretion of lithostathine, a pancreatic glycoprotein capable of
      inhibiting the growth of CaCO3 crystals, has been reported in chronic calcifying
      pancreatitis. Controversial results were obtained, however, using immunoassays
      with different antibodies. The aim of this study was to purify and to measure
      juice lithostathine by a non-immunological method. Fast protein liquid
      chromatography (FPLC) on a cation exchange column eluted by a sodium chloride
      gradient, was used. The conditions appropriate to separate secretory (S) from
      hydrolysed (H) isoforms of immunopurified lithostathine were also used for juice
      analysis. Pancreatic juice was collected by endoscopic cannulation of the major
      pancreatic duct, after secretin stimulation, from eight patients with chronic
      pancreatitis (CP) and from eight controls. In all samples, S-isoforms of
      lithostathine (ranging from 16 to 19 Mr at SDS-PAGE) were the only constituent of
      two of the 15 peaks in which FPLC resolved the pancreatic proteins. The nature of
      these two peaks was confirmed by their coelution with immunopurified S
      lithostathine and by immunoblot analysis with polyclonal anti-lithostathine
      antibodies. The ratio between the area of S-lithostathine peaks and the total
      area of proteic eluates, was always lower in CP patients (5.3 micrograms/mg of
      protein, median value; 0.2-15.4, range) than in controls (35.2 micrograms/mg;
      16.6-55.9). It is concluded that lithostathine can be purified and measured in
      pancreatic juice by FPLC. Our results with a nonimmunological assay confirm a
      reduced secretion of lithostathine in patients with CP.

PMID- 7737576
TI  - European cooperation in gastroenterology.

PMID- 7737575
TI  - Quantification of human lithostathine by high performance liquid chromatography.
AB  - Pancreatic stones of patients with chronic calcifying pancreatitis (CCP) are
      mostly made up of CaCO3 crystals. Formation and growth of such crystals is
      inhibited in vitro by lithostathine, a protein present in normal pancreatic
      juice. Decreased lithostathine activity was therefore suspected in patients with
      CCP, but comparison by immunoassay of lithostathine concentrations in the
      pancreatic juices of patients and controls led to conflicting results. This study
      shows that these discrepancies might have been caused in part by a remarkably
      high susceptibility of the protein to trypsin like cleavage, resulting in
      important structural changes and concomitant modifications of the epitopes. A
      novel lithostathine assay in juice was developed, based on separation of
      secretory proteins by high performance liquid chromatography. The chromatographic
      separation of lithostathine was based on hydrophobic interactions at pH 5.0 using
      a Phenyl-TSK column. This study showed with this assay that lithostathine
      concentrations (microgram/mg of total protein) were similar in CCP patients with
      alcoholic aetiology (mean (SD) 6.3 (2.7)) and other aetiologies (7.2 (3.7)), but
      one third of those estimated in patients without pancreatic disease (16.7 (4.3)).
      Similar concentrations were found, however, in chronic alcoholic patients without
      CCP (6.6 (3.3)) and in patients with CCP. It was concluded that decreased
      lithostathine concentration is associated with CCP, although such a decrease is
      not sufficient by itself for the disease to occur.

PMID- 7737577
TI  - An alternative view of 5-ASA formulations.

PMID- 7737578
TI  - New salicylates as maintenance treatment in ulcerative colitis.

PMID- 7737579
TI  - Tobacco smoking and the uterine cervix: cotinine in blood, urine and cervical
      fluid.
AB  - Cotinine levels in blood, urine and cervical fluid of smokers and nonsmokers were
      analyzed by capillary-column gas chromatography. The sensitivity of this method
      appeared to be 100%. The specificity was lower (87.5% in blood, 25% in urine and
      75% in cervical fluid). Nonsmokers exposed to smoke by others had low but
      detectable cotinine levels in the three body fluids. The highest cotinine levels
      in cervical fluid were detected during the proliferative phase of the cycle.
      Cotinine levels in cervical fluid and blood correlated well, but the correlation
      was less during the proliferation phase. Cotinine measurement in cervical fluid
      proves to be a reliable method to quantify exposure to tobacco smoke, even when
      induced by others.

PMID- 7737580
TI  - The combined effect of a GnRH analog in premenopause plus postmenopausal estrogen
      deficiency for the treatment of uterine leiomyomas in perimenopausal women.
AB  - Thirty-four perimenopausal women with uterine leiomyomas were treated with
      intramuscular injections of leuprolide acetate depot each 28 days for 6 cycles,
      and 12 of them after 168 days of no medication underwent a second 6-month therapy
      cycle. At the end of the observation period the expected improvement during
      treatment was maintained at cessation of therapy in 15 patients, due to the
      effect of the natural postmenopausal estrogen deficiency. Only 3 women underwent
      hysterectomy, due to the regrowth to baseline values of uterine size. It is
      concluded that the therapy with gonadotropin-releasing hormone analogs in
      perimenopause offers an effective alternative to surgery in the treatment of
      uterine leiomyomas.

PMID- 7737581
TI  - Ki-67 immunostaining of endometrial biopsies with special reference to hormone
      replacement therapy.
AB  - BACKGROUND: The purpose of this investigation was to evaluate the Ki-67
      immunostaining method on formalin-fixed, paraffin-embedded endometrium and to use
      the method on endometrial biopsies from 30 postmenopausal women treated with 2 mg
      estradiol and different doses of natural micronized progesterone (50, 100 or 200
      mg). METHODS: Two technicians prepared the immunostaining of slides from each of
      12 endometrial specimens and 3 different observers estimated the Ki-67
      immunostaining. One observer estimated all the slides 3 times on different
      occasions. The percentage of immunopositive nuclei in glandular epithelium was
      evaluated. RESULTS: The dominating component of variation for this method was
      between observers, with a median standard deviation of 20%. A total median
      variation including all components rendered a standard deviation of 23%. No
      significant effects of different technicians, preparations, or from the same
      observer on different occasions were found. In the major part of the biopsies
      from women on hormone replacement therapy (HRT), only 0-10% of the glandular
      epithelium was Ki-67 stained. CONCLUSION: Ki-67 immunostaining is an adequate
      technique to use when evaluating the effects of HRT on the endometrium. The main
      source of variation is between observers and not the technique of preparing the
      slides.

PMID- 7737583
TI  - HPV DNA positivity and natural killer cell activity in the clinical outcome of
      mild cervical dysplasia: integration between virus and immune system.
AB  - The objective was to examine the prevalence of human papillomavirus (HPV) DNA
      infection in mild cervical dysplasia and to evaluate longitudinally the
      persistence of HPV DNA positivity in an observational study, aiming at
      identifying the role of peripheral blood lymphocyte natural killer activity in
      the natural history of dysplastic disease. Twenty-three patients with
      histologically proven mild cervical dysplasia were selected. The HPV DNA
      positivity, determined by polymerase chain reaction, and cervical dysplasia were
      monitored cytologically and colposcopically at the 3rd (time 1), 6th (time 2) and
      12th months (time 3), and defined by biopsies for routine histology taken at
      times 2 and 3. For each patient included in the study, the immune reactivity was
      evaluated at the time of diagnosis and afterwards, longitudinally during the
      follow-up. The immune status analysis included T lymphocyte subsets (CD3, CD4,
      CD8, CD56, CD16 monoclonal antibodies by Beckton Dickinson, Mountain View,
      Calif., USA) and determinations of natural killer cell activity (against the
      sensitive cell line K 562). Eighteen out of the 23 women with mild cervical
      dysplasia (78.3%) were found positive for HPV DNA, with a significantly high
      representation of HPV DNA type 16 (55.6% of cases). At the end of the study, 12
      out of 18 HPV-DNA-positive women became negative (defined by two or more negative
      tests) for the original HPV DNA type, with 66.7% of spontaneous HPV DNA
      negativization rate (p = 0.6).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737582
TI  - Clinical value of a new serum tumor marker, CA125II, in gynecologic disease:
      comparison with CA125.
AB  - CA125 II, an improved version of the conventional CA125 was compared with CA125
      as to which was more useful in gynecologic disease. In the diagnosis of tumors
      around the adnexal field (primary epithelial ovarian cancer, metastatic ovarian
      cancer, benign ovarian tumor and endometrial cyst), CA125 II showed the same
      sensitivity and specificity as CA125. CA125 II also has high simultaneous
      reproducibility in the low concentration area. The examination by the receiver
      operating characteristic curve revealed that CA125 II has higher precision than
      that of CA125 when it is used for the screening test. In conclusion, CA125 II is
      a better tumor marker than conventional CA125.

PMID- 7737585
TI  - Prenatally diagnosed female prune belly syndrome associated with tetralogy of
      Fallot.
AB  - Female prune belly syndrome and tetralogy of Fallot were diagnosed in obstetric
      ultrasound screening at 13 and 28 weeks of gestation, respectively. The baby was
      born at 38 weeks showing abdominal distension, hypoplasia of abdominal muscles,
      vaginal atresia, imperforate anus and clubfeet. Radiologic and ultrasound
      examinations confirmed our prenatal diagnosis and revealed other abnormalities of
      patent ductus arteriosus, major aortopulmonary collateral arteries, bilateral
      vesicoureteral reflux, rectourethral fistula and hypoplasia of the right kidney.
      Urination has been smooth, but cystitis was observed repeatedly once a month. The
      infant was discharged in good condition and has been followed in the outpatient
      clinic.

PMID- 7737584
TI  - Morphologic criteria for the prognosis of serous cystadenocarcinoma of the ovary.
AB  - 143 cases of serous ovarian cystadenocarcinoma were studied to establish the
      prognostic relevance of specific macroscopic and microscopic criteria.
      Significant differences in the survival rate were found depending on TNM
      classification, age, residual tumor mass, ascites, and degree of invasion. The
      prognosis was significantly better for normotypical or predominantly cystic
      tumors as well as for those with mononuclear infiltration, little histological
      atypia, or limited invasion. No prognostic relevance was found, however, for
      cytologic criteria such as Broder's grading and rate of mitosis.

PMID- 7737586
TI  - Prostaglandin G/H synthase-1 messenger RNA relative abundance in human amnion,
      choriodecidua and placenta before, during and after spontaneous-onset labour at
      term.
AB  - The aim of this study was to determine the relative abundance of prostaglandin
      G/H synthase-1 (PGHS-1) mRNA in human amnion, choriodecidua and placenta obtained
      before (n = 5), during (n = 5) and after spontaneous-onset labour and delivery at
      term (n = 5). PGHS-1 mRNA relative abundance was not affected by labour status (p
      > 0.1) nor differently expressed between gestational tissues (p > 0.05). These
      data are consistent with the hypothesis that PGHS-1 is a constitutively expressed
      isozyme and that an increase in the relative abundance of mRNA encoding this
      enzyme is not necessary for the labour-associated increase in prostaglandin
      formation.

PMID- 7737588
TI  - Relation between erythropoietin and vitamin B12 in normal and anemic pregnant
      women.
AB  - In this cross-sectional study of 178 pregnant women between the 7th and 42nd week
      of pregnancy, we analyzed correlations between erythropoietin (EPO) and vitamin
      B12 (B12) in different stages of pregnancy and in relation to hemoglobin (Hb)
      levels. Patients with hypertension, fetal growth retardation and severe systemic
      diseases were excluded. EPO (by ELISA), B12 (by RIA) and Hb were assayed in the
      same blood sample taken on admission. On the basis of weeks of pregnancy, EPO
      levels and B12 levels, the 178 subjects were found to fall into two clusters,
      before and after the 27th week of gestation. The correlation coefficient between
      EPO and B12 was highly significant in the first group but not in the second (R = 
      0.33; p < 0.01). When the patients were divided on the basis of Hb levels (< or =
      or > 11 g/dl), a significant correlation was found only in the 88 patients with
      Hb > 11 g/dl (R = -0.44; p < 0.001) and not in the 72 anemic subjects. Moreover,
      in the former group the correlation between EPO and B12 was high before and after
      the 27th week, unlike in the latter group for which no significant correlation
      was found. These results suggest that EPO and B12 act together to establish
      normal erythropoiesis in pregnancy.

PMID- 7737587
TI  - Activation of complement in humans with a first-trimester pregnancy loss.
AB  - Serum complement (C') activity in recurrent spontaneous aborters and primiparous
      controls with successful and unsuccessful pregnancies was quantified so as to
      define the dynamics of C' activation in early pregnancy loss. C' hemolytic
      activity was shown to be stable throughout the first trimester of pregnancy and
      did not differ from preconception levels in all of the successful pregnancies of
      recurrent aborters and controls and in the majority of pregnancy losses. However,
      30% of recurrent aborters and 20% of controls with a pregnancy loss demonstrated
      activation of C' by the alternate pathway as early as the 7th week with a
      progressive decline in C' activity until abortion was clinically completed.
      Circulating levels of C3 dropped from 1.34 to 0.53 mg/dl, and factor B levels
      declined from 0.34 to 0.14 mg/dl in these hypocomplementemic women. Pregnancy
      loss is therefore associated with C' activation in a subset of both recurrent and
      nonrecurrent aborters and this occurs largely before loss of fetal viability.

PMID- 7737589
TI  - Maternal plasma endothelin levels and fetal status in normal and preeclamptic
      pregnancies.
AB  - Endothelin (ET) is a potent vasoconstrictor peptide. In this study, we
      investigated maternal venous plasma ET levels measured by Sandwich-enzyme
      immunoassay within a week before the onset of labor, and measured plasma renin
      activity and plasma aldosterone concentration by radioimmunoassay in normal and
      severely preeclamptic pregnancies. Also, we determined umbilical cord blood pH
      and gas concentrations after spontaneous vaginal deliveries and cesarean
      sections. There was a significant (p < 0.01) negative correlation between
      maternal ET levels within 1 week before the onset of labor and birth weights.
      There was no significant correlation between maternal ET levels and umbilical gas
      concentrations. These data suggest that the correlation is the result of
      decreasing uteroplacental blood flow. We speculate that increased maternal ET
      expresses not only maternal renal vascular endothelial injury but also other
      vascular endothelial injuries. These vascular injuries may occur at least 1 week
      before the clinical manifestation in the preeclamptic mothers and their fetuses.

PMID- 7737590
TI  - Tissue plasminogen activator and plasminogen activator inhibitors of types 1 and
      2 in amniotic fluid before labour and after childbirth.
AB  - We measured three selected components of the fibrinolytic system in amniotic
      fluid of 36 parturient women, i.e. the antigen of tissue plasminogen activator
      (tPA) and antigens of plasminogen activator inhibitor of type 1 (PAI-1) and type
      2 (PAI-2). The ELISA method was used. During labour, the level of each of the
      studied antigens increases; tPA antigen increases over five times (0.91 +/- 0.32
      ng/ml before labour and 5.92 +/- 1.83 ng/ml after childbirth), which is
      statistically significant, while at the same time the increase in PAI-1 and PAI-2
      antigen levels is small and thus statistically insignificant. As the result of
      unequal changes, the prelabour dominance of PAIs over tPA decreases intra partum
      (tPA/PAIs ratio 1:1,038 before labour and 1:164 after childbirth), and yet the
      multiple dominance of PAIs over tPA remains.

PMID- 7737591
TI  - [Lactitol suppresses the disturbance of consciousness caused by experimentally
      induced hepatic encephalopathy in rats: an EEG study].
AB  - Electroencephalographic (EEG) studies were conducted to demonstrate the
      ameliorating effects of lactitol and its reference drug lactulose on the
      disturbance of consciousness caused by severe hepatic encephalopathy in rats
      permanently implanted with cortical electrodes. A novel experimental animal model
      of combined-type human hepatic encephalopathy was prepared by portacaval shunting
      followed by a single treatment with dimethylnitrosamine (30 mg/kg, i.p.).
      Lactitol or lactulose was orally administered twice a day for seven days and once
      on the morning of the eighth day. Ammonium acetate (500 mg/kg) was injected into
      the cecum 4 hr after the final administration of the drug. In control animals not
      treated with either drug, but in which hepatic encephalopathy had been induced,
      ammonium acetate induced a comatose state defined by a loss of the righting
      reflex accompanied by slowing or flattening of the cortical EEG. In control
      animals, significant increases in delta (1-3 Hz)-activity and significant
      decreases in beta (13-25 Hz)-activity during coma were detected by means of EEG
      power spectral analysis. Lactitol at doses of 3 g/kg/day or higher or lactulose
      at 6 g/kg/day significantly suppressed these EEG changes. Both drugs also
      suppressed in a dose-dependent manner the loss of the righting reflex. Lactitol
      may therefore be useful for ameliorating the disturbance of consciousness in
      patients with hepatic encephalopathy.

PMID- 7737592
TI  - [Cough--diversity and the peripheral mechanisms of production].
AB  - The physiology and pharmacology of the cough reflex were reviewed from the
      perspective that the cough response and its peripheral mechanisms have diversity,
      taking reported findings together with the results obtained from our own studies.
      It is clear that there was a remarkable difference in the magnitude of expiration
      and sound in coughing between the two types of coughs in guinea pigs: one is
      caused by mechanical irritation to the airway mucosa or citric acid inhalation
      and the other caused by inhalation of pharmacological agents such as capsaicin
      and substance P. Four types of stimulation, i.e., mechanical, physicochemical,
      chemical and pharmacological stimulation, were discussed with respect to the site
      and the mechanisms of action in the airway. Mechanical stimulants and chemical
      stimulants such as citric acid seem to act mainly on A delta-fibers. However, it
      is unclear whether pharmacological agents act on C-fibers to produce cough. As to
      the difference in distribution of cough receptors in the airway, pharmacological
      differences were found between coughs caused by mechanical irritation on the
      laryngeal sites and the site of bifurcation of the trachea. Furthermore,
      capsaicin, applied by a topical spraying method newly developed by us, produced
      cough-like forced expiration when it was sprayed around the site of the
      bifurcation of the trachea. This response was not depressed by codeine, but
      depressed by ophiopogonin, a Chinese herbal antitussive; mephenesine; and a
      neurokinin A antagonist. Mechanisms of cough augmentation in bronchitic guinea
      pigs were also described briefly. In conclusion, the site of action of cough
      stimulants and the mechanisms of cough production are still controversial. To
      solve these problems, we need to develop new methods and strategies for studying
      the cough reflex.

PMID- 7737593
TI  - [Pharmacology of glibenclamide-sensitive K+ channels in follicle-enclosed Xenopus
      oocytes].
AB  - Follicle-enclosed Xenopus oocytes have endogenous glibenclamide-sensitive K+
      channels that can be activated by K+ channel openers. Since the follicle-enclosed
      Xenopus oocytes can be easily voltage-clamped, the K+ channels are used as a
      model of the ATP/glibenclamide-sensitive K+ channels. So far, the effects of
      calmodulin antagonists, antiarrhythmics, anesthetics, antidepressants, histamine
      H1-receptor antagonists, imidazolines and several hormones on the K+ channels of
      the oocytes have been reported. The pharmacological data on the K+ channels
      obtained from the oocyte-system may contribute to our understanding of the
      regulatory mechanism and physiological role of the ATP/glibenclamide-sensitive K+
      channels.

PMID- 7737594
TI  - [Effects of Onpi-to (TJ-8117) on mesangial injury induced by anti Thy-1
      antibody].
AB  - We investigated the effect of Onpi-to (TJ-8117) on the mesangial injury induced
      by anti-Thy-1 antibody. TJ-8117 (400 mg/kg/day, p.o.) given from the 1st day
      (from the day of injection of the anti-thymocyte serum) or 4th day (after
      mesangial proliferation), markedly inhibited the mesangial proliferation and
      hypercellularity in glomeruli. TJ-8117 prevented the increase in the number of
      PCNA or ED-1 positive cells in glomeruli. These results suggest that TJ-8117 is
      effective against glomerular disease with mesangial injury.

PMID- 7737595
TI  - [Protective effects of LipoPGE1, prostaglandin E1 incorporated in lipid
      microspheres, against liver injury caused by ischemia-reperfusion].
AB  - Effect of LipoPGE1 on liver injury caused by ischemia-reperfusion were compared
      with that of PGE1-CD, cyclodextrin clathrated PGE1, in rats. LipoPGE1 (10
      micrograms/kg) and PGE1-CD (10 micrograms/kg) were gradually injected into the
      portal vein 5 min both prior to ischemia and prior to reperfusion. In only the
      group receiving injections of vehicle alone, rats died within 2 days after the
      episode of 90-min liver ischemia. The survival rate of all rats treated with
      LipoPGE1 was higher than that of rats who received vehicle alone, which indicates
      that LipoPGE1 pretherapy improved the survival of rats after liver ischemia
      reperfusion. LipoPGE1 markedly suppressed elevations of GOT, GPT, and LDH, lipid
      peroxide and aromatic amino acid levels in the plasma caused by ischemia
      reperfusion of the liver. When animals were given a single dose of LipoPGE1 prior
      to reperfusion, LipoPGE1 also suppressed elevations of GOT, GPT, LDH and lipid
      peroxide levels caused by 30-min of liver ischemia followed by 12-hr reperfusion.
      These suppressive effects with LipoPGE1 were stronger than those of PGE1-CD.
      These findings suggest that LipoPGE1 may have therapeutic applications in the
      treatment of hepatic injury.

PMID- 7737596
TI  - [Effect of an extract prepared from "dai-bofu-to" on morphine withdrawal
      responses].
AB  - A water-extract (TJ-97) prepared from "Dai-bofu-to", a "Kampo" medicine (Chinese
      traditional prescriptions composed of herbal drugs) was tested for its potency to
      modulate morphine withdrawal responses in animals. TJ-97 significantly attenuated
      naloxone-induced contraction of the segments of the ileum isolated from morphine
      dependent guinea pigs in the absence and presence of atropine. TJ-97 also
      inhibited the contractile responses of the segments to electrical field
      stimulation at a low frequency and those to nicotine, but not those to
      exogenously applied ACh or substance P. The rats given i.p. TJ-97 and 30 min
      later challenged with naloxone showed significantly lowered frequency of
      excretion and diminished amount of feces, including soft stools (diarrhea), as
      compared with the saline-injected control rats. These findings suggest that TJ-97
      inhibits the release of ACh and substance P or substance P-like peptide(s) from
      the nervous structures in the wall of the ileum.

PMID- 7737597
TI  - [Effect of lactitol (NS-4) on the increase in blood and brain ammonia
      concentration and on coma in newly developed rat models of hepatic coma].
AB  - Encephalopathy caused by hepatic cirrhosis is often associated with portasystemic
      shunt and hepatic parenchymal injury. Together, these are known as a combined
      type symptom. Two experimental hepatic comatose models with combined-type symptom
      were developed in rats. Both of these models involve the administration of
      ammonium acetate (500 mg/kg) into the cecum in portacaval shunted (PCS) rats. In
      addition, hepatic injury was induced in one model by carbontetrachloride (CCl4)
      and in the other by dimethylnitrosamine (DMNA). These model rats showed a higher
      increase in the concentration of ammonia in the blood and a higher incidence of
      coma as determined by the loss of the righting reflex than did rats subjected to
      a shunt only (PCS operation + ammonia loading) or hepatic parenchymal injury only
      (CCl4 treatment + ammonia loading). The effect of lactitol, administered orally
      for 7.5 days, on the experimental hepatic coma was compared with that of
      lactulose. Lactitol significantly inhibited the increase in blood and brain
      ammonia concentration at doses of 3 and 6 g/kg/day and also reduced the incidence
      of coma. The effects of lactitol were similar to those of lactulose, a
      therapeutic agent for hepatic encephalopathy. Therefore, lactitol should be
      useful in the clinical treatment of hyperammonemia or hepatic encephalopathy.

PMID- 7737598
TI  - Human diets cooked by microwave or conventionally: comparative sub-chronic (13
      wk) toxicity study in rats.
AB  - To compare the possible effects of microwave and conventional cooking on a range
      of common dietary components, mixed human diets containing beef, potatoes and
      vegetables were fed to groups of 10 male and 10 female Wistar rats for 13 wk. The
      diet ingredients were cooked by either of the methods in a normal and an abused
      manner, the latter consisting of the normal treatment followed by two cycles of
      reheating to approximately 85 degrees C and cooling. The cooked ingredients were
      freeze-dried, ground and mixed with supplements of vitamins and minerals to meet
      the rat requirements. An additional control group was fed a cereal-based rodent
      diet. Criteria to assess toxicity included clinical observations, ophthalmoscopy,
      growth, food and water intake, haematology, clinical chemistry, urinalysis, organ
      weights, micronucleated erythrocytes in bone marrow, gross examination at autopsy
      and microscopic examination of a wide range of organs. The results indicate no
      adverse effects of the diets cooked by microwave compared with those cooked
      conventionally.

PMID- 7737599
TI  - Genotoxicity of agaritine in the lacI transgenic mouse mutation assay: evaluation
      of the health risk of mushroom consumption.
AB  - The mutagenic potency of the common mushroom Agaricus bisporus and crude
      agaritine extracted from mushrooms was determined in vivo using a new mutagenesis
      assay with lacI transgenic mice (Big Blue mice). Pairs of female lacI mice were
      fed one of three diets for 15 wk: (1) fresh mushrooms 3 days/wk followed by
      normal lab chow for 4 days/wk; (2) freeze-dried mushrooms mixed at 25% (w/w) into
      powdered chow; or (3) a mushroom extract containing 30% agaritine (w/w) mixed
      into powdered chow. The corresponding daily doses of agaritine were 30 (averaged
      over the whole week), 80 and 120 mg/kg body weight, respectively. Positive
      control animals received N-nitrosodimethylamine, N-nitrosomethylurea or urethane,
      mixed into powdered chow at concentrations corresponding to daily doses of 0.3, 3
      and 130 mg/kg body weight, respectively. DNA of the forestomach, kidney, liver,
      lung and glandular stomach of the lacI mice was examined for increases in mutant
      frequency (MF). Control MFs ranged from 5 x 10(-5) to 10 x 10(-5). Positive
      control substances induced a two- to seven-fold increase in MF in their
      respective target organs. Of the mushroom diets, significant effects were seen
      only with the crude agaritine extract: it induced an increase in MF of 100% in
      the kidney and 50% in the forestomach. The other two A. bisporus diets, with
      lower agaritine doses, showed slightly but not significantly, raised MF values in
      the kidney alone. Thus, agaritine was weakly genotoxic in vivo; no genotoxic
      activity other than that attributable to agaritine was detected in A. bisporus.
      Substances or processes that might influence carcinogenicity by means of non
      genotoxic mechanisms (e.g. increase in fibre, or decrease in calorie intake) are
      not detected in the lacI assay. Using a previously derived quantitative
      correlation between mutagenicity in the lacI test and carcinogenic potency, the
      carcinogenicity of agaritine in mushrooms was estimated: the average Swiss
      mushroom consumption of 4 g/day would be expected to contribute a lifetime
      cumulative cancer risk of about two cases per 100,000 lives.

PMID- 7737600
TI  - Changes in dimensions and mechanical properties of bone in chicks fed high levels
      of niacin.
AB  - Tibia dimensions and mechanical properties were determined in White Leghorn
      cockerels that had been fed from 0.1 to 2.0% niacin as a supplement to standard
      poultry diets. Four experiments of from 20 to 38 days were conducted. No
      significant differences due to niacin were found in weight gain, feed consumed or
      feed:gain ratios. Decreases in the exterior (P < 0.009) and interior (P < 0.015)
      diameters of the major axes of the tibiae were found at 0.75-2.0% niacin.
      Exterior (P < 0.005) and interior (P < 0.001) diameters of the minor axes of the
      tibia were decreased at levels of 0.75 and 1%. Changes occurred in lateral wall
      thickness of chicks fed 0.75% niacin for 20 days (P < 0.004) and 38 days (P <
      0.023) and in anterior wall thickness of 6-month-old chickens fed 1.0% niacin for
      28 days (P < 0.001). Ultimate force was decreased in young chicks fed 1.0 and
      1.5% niacin (P < 0.014) and 6-month-old White Leghorn chickens fed 1.0% niacin (P
      < 0.004). The addition of high levels of niacin to chick rations resulted in
      changes in dimensions, bone strength and susceptibility to fracture.

PMID- 7737601
TI  - Safety assessment of polylactide (PLA) for use as a food-contact polymer.
AB  - This report constitutes a safety assessment of polylactide (PLA), a polymer of
      lactic acid intended for use in fabricating various food-contact articles.
      Migration studies were conducted on samples of the polymer following guidelines
      issued by the Food and Drug Administration. Potential migrants from PLA include
      lactic acid, lactide (the monomer), and lactoyllactic acid (the linear dimer of
      lactic acid). The studies were designed to model reasonable 'worst' case
      extraction situations when the polymer is used (a) in houseware articles for
      short and intermediate time periods at various temperatures and (b) in food
      packaging materials. The limited migration observed during the trials represents
      no significant risk since migrating species are expected to convert to lactic
      acid, a safe food substance. It is concluded that PLA is safe and 'Generally
      Recognized As Safe' for its intended uses as a polymer for fabricating articles
      that will hold and/or package food.

PMID- 7737602
TI  - Inhalation teratology and two-generation reproduction studies with 1,1-dichloro-1
      fluoroethane (HCFC-141b).
AB  - HCFC-141b is one of the chemicals being considered as a replacement for CFC 11 in
      solvent and foam-blowing applications. Teratology studies were conducted in both
      rats and rabbits and a two-generation reproduction inhalation toxicity study was
      conducted in rats. The pregnant rabbits were exposed to levels of 0 (control),
      1400, 4200 and 12,600 ppm HCFC-141b from day 7 to day 19 of gestation (6 hr/day).
      There was no evidence of developmental or teratogenic effects on the foetuses.
      The pregnant rats in the teratology study were exposed to levels of 0 (control),
      3200, 8000 and 20,000 ppm from days 6 to 15 of gestation (6 hr/day). In the
      20,000 ppm exposure group, there was an increase in implantation losses;
      furthermore, in this group, foetal weights tended to be lower than controls. As
      with the rabbits, there was no evidence of a teratogenic effect. The reproduction
      study was conducted at exposure levels of 0, 2000, 8000 and 20,000 ppm, 7 days/wk
      starting approximately 10 wk before the first pairing. Adult rats exposed at
      20,000 ppm (and, to a lesser extent, those exposed to 8000 ppm) showed increases
      in water intake, slight increases in food consumption, and decreases in body
      weight. Following the mating of the F0 parents, there were fewer litters in the
      20,000 ppm exposure level group than in controls. When these parents were then
      paired with different partners, again, the number of litters was lower in the
      20,000 ppm group, although most of the animals that did not produce litters the
      first time mated successfully the second time. When the F1 animals were mated to
      produce the second generation, the number of litters was comparable for all
      groups. In the second F0 mating and the F1 mating, the number of pups per litter
      was lower at 20,000 ppm; although birth weights were comparable, body weight gain
      tended to be slower in the high-level exposure group. Survival was good in all
      groups. At 8000 ppm no significant effects were observed in the pups and only
      minimal signs in the adults. The 2000 ppm exposure level represented a clear no
      observed-effect level for all indices.

PMID- 7737604
TI  - Percutaneous penetration of dimethylnitrosamine through human skin in vitro:
      application from cosmetic vehicles.
AB  - Human skin penetration of N-dimethylnitrosamine (DMN) from three vehicles has
      been determined in vitro. When applied as an infinite dose in isopropyl myristate
      (IPM, 1 microgram/microliter) the average total absorption over 48 hr was 2.6 +/-
      1.2% of the applied dose (all data presented are expressed as means +/- standard
      errors). When applied as a finite dose in a representative oil-in-water emulsion
      vehicle the average total absorption over 48 hr was 4.0 +/- 0.3% of the applied
      dose. When applied as a finite dose in a representative shampoo vehicle for 10
      min followed by rinsing (i.e. to represent in-use exposure conditions) the
      average total absorption over 48 hr was 1.1 +/- 0.1% of the applied dose.
      Approximately 72% of the DMN in the applied shampoo vehicle was removed by
      rinsing. There was considerable evaporative loss of DMN from the IPM and oil-in
      water emulsion vehicles, such that absorption was complete within 3 hr of
      application. The overall data indicate that DMN can penetrate the skin rapidly
      but that in practice the amount actually available for penetration is
      significantly reduced by high permeant volatility. In contrast, application of N
      nitrosodiethanolamine (NDELA) at a concentration of 1 microgram/microliter as an
      infinite dose generated an average total absorption over 48 hr of 23.6 +/- 6.4%,
      representing a total flux of 103.9 +/- 28.4 micrograms/cm2. In the case of NDELA,
      no evaporative loss was evident.

PMID- 7737605
TI  - The glycoalkaloids: naturally of interest (but a hot potato?).

PMID- 7737603
TI  - Oxidative stress-regulated gene expression and promotion of morphological
      transformation induced in C3H/10T1/2 cells by ammonium metavanadate.
AB  - Promoters of C3H/10T1/2 cell morphological transformation that elevate
      intracellular oxidant levels can be distinguished by a spectrum of induced gene
      expression, which includes the oxidant-responsive murine proliferin gene family.
      Proliferin transcripts were induced 40- to 100-fold by 20 microM ammonium
      metavanadate, 20-fold by 5 microM vanadium pentoxide but only three-fold by
      vanadium oxide sulfate. Consistent with its response to other oxidant chemicals,
      induction of proliferin by ammonium metavanadate was inhibited almost completely
      by the antioxidant N-acetylcysteine (8 mM). Ammonium metavanadate (5 microM),
      added as promoter in two-stage morphological transformation assays, amplified
      yields of Type II and Type III foci in monolayers of 20-methylcholanthrene
      initiated C3H/10T1/2 cells. Ammonium metavanadate also induced formation of Type
      II foci in single-step transformation assays. The results suggest that
      pentavalent vanadium compounds could promote morphological transformation in
      C3H/10T1/2 cells by creating a cellular state of oxidative stress, sufficient to
      induce elevated expression of the proliferin gene family.

PMID- 7737606
TI  - Genetic events in the development of colon cancer.

PMID- 7737607
TI  - Microbiological endpoint testing for veterinary antimicrobials--setting MRLs.

PMID- 7737608
TI  - Committees on toxicity, mutagenicity and carcinogenicity.

PMID- 7737609
TI  - [The force transmission of positioners in different degrees of incisor
      protrusion. An in-vitro study].
AB  - The purpose of this study was to examine the forces exerted on protruded upper
      incisors by tooth positioners. Methodologically an in vitro force measurement
      model was used. The tooth positioners were made of 7 readily available materials
      commonly used in orthodontics. The study found that the values of the forces,
      which ranged from 0.4 N to 14.0 N per tooth, are dependent on the material used
      and the degree of tooth protrusion. In addition, the study analyzed the changes
      in force over a 3-month period during which time the positioners were stored at
      37 degrees +/- 1 degree C in an aqueous environment. This environment corresponds
      closely to that found in the mouth.

PMID- 7737610
TI  - [Improvement in the adhesive strength of orthodontic brackets on unit-cast and
      fired dental alloys by microsandblasting].
AB  - This experimental study employed an Instron test machine to measure the bond
      strength of metal brackets to cast test specimens made of 6 different dental
      alloys. An easily replicated method for testing the shear bond strength is
      presented, which corresponds to the international recommendations for testing
      bond strength of orthodontic brackets. The study found that the different methods
      of surface preparation, such as micro-sandblasting and the use of chemical
      sealants, had distinct effects on the magnitude of bond strength gauged. Also
      tested was whether the storage medium prior to debonding influenced the bond
      strength. The measured values from a series of tested bovine teeth, which were
      bonded by means of the conventional acid etch method and with the same adhesive,
      served as a control group. An extended statistical analysis showed that the use
      of the methods described can achieve a clinically acceptable bond of brackets to
      dental alloys for prosthetic restorations.

PMID- 7737611
TI  - [A holographic study to demonstrate the initial displacements of a macerated
      human skull under the influence of the orthodontic force from headgear with
      traction in different directions].
AB  - The phenomena of maxillary displacement and the subsequent growth modifications
      which result from the application of orthopedic headgear traction are very
      complex and not yet completely understood. The aim of this study was to
      investigate with the help of holographic interferometry the influence of the
      headgear's differing traction directions on the initial bone displacement in the
      maxillary complex. 560 g high, straight, and low pull headgear traction exerted
      above, through, and below the center of resistance of the upper first permanent
      molars was simulated on a macerated human skull and skeletal changes were
      recorded by laser holography as they occurred. On the basis of the frontal and
      lateral holograms thus obtained, the initial displacement of the maxilla, zygoma,
      and zygomatic arch in both horizontal and vertical planes was evaluated.
      Substantial displacements in various parts of the studied structures,
      displacements such as bending, relative deformation, rotation, and translation,
      were detected, and, further, the direction of this complex displacement often
      deviated from the direction of the influencing force. The results obtained by
      this study indicate that the initial 3-dimensional skeletal displacements brought
      about by the headgear are very complex. The clinical implication is that they do
      not always correspond with the direction intended by the force applied.

PMID- 7737612
TI  - [Follow-up study of dyskinesia-induced dysgnathias following myofunctional
      therapy].
AB  - Forty-eight patients with dysgnathia brought about by tongue dyskinesia underwent
      myofunctional therapy leading up to and at the beginning of orthodontic
      treatment. Short- and long-term results of this therapy were studied with the
      help of indirect palatography. Palatographs of empty swallowing and the test
      consonants "L", "N", "S" and "T" were evaluated visually and metrically. The
      palatographs were made prior to myofunctional therapy and thereafter first at the
      end of the therapy, then at the end of the control or supervision period, and
      finally, after on average 4 years. Visual evaluation revealed a clearly
      recognizable change in all functions when compared with the physiological
      palatographs. A change in the "S" consonant sound was the least conspicuous.
      Metric evaluation revealed for the 4 out of 5 of the test functions, namely,
      empty swallowing and the consonants "L", "N", and "T", marked long-term dorsal
      orientation of the tongue. The short-term changes in tongue function were more
      prevalent than the long-term.

PMID- 7737613
TI  - [The psychosocial aspects in orthodontically treated and untreated adults with
      similar, clearly visible tooth malalignments].
AB  - A study was undertaken to compare the psychosocial aspects of orthodontic
      treatment or non-treatment of female adults, 25 of whom underwent treatment and
      25 of whom did not, with similar, visible malocclusion. Interviews, for which 52
      standardized questions were prepared in collaboration with a graduate
      psychologist, served as the methodological basis of the study. The results of the
      study indicate that in relation to the aesthetic aspects of orthodontic
      treatment, the treated group showed a high degree of sensitivity and self
      perception. Following orthodontic treatment members of this group exhibited a
      highly significant improvement in their subjective perception of the aesthetic
      aspects of their dental and facial appearance. In spite of the differences
      observed in the 2 groups, it nevertheless remains difficult to draw general
      conclusions or to recommend guidelines which would cover all cases. When the
      question is to orthodontically treat or not treat female adults, the answer rests
      with the individual patient.

PMID- 7737614
TI  - [The importance of hand x-rays for the treatment of skeletal dysgnathias].
AB  - This study demonstrates the importance of X-rays of the hand in assessing
      skeletal changes in jaw relationships. The study is based on a follow-up
      examination of 53 patients with skeletal class II,1-, skeletal class II,2-, class
      III and skeletal open bite malocclusions who had been treated orthodontically.
      Statistical analysis of the growth parameters found a significant correlation
      between chronological age and skeletal age with considerable deviations depending
      on sex. At the end of the treatment period it was observed that 34% of all
      patients had not reached the end of puberty and had not achieved a mature level
      of growth. During the post-therapeutical period, growth was found on average to
      be 2.4% in the girls and up to 4.7% in the boys. When looking at the influence of
      growth and therapy, the patient group with skeletal class II,1 malocclusion
      exhibited at both therapeutical and post-therapeutical examinations a very
      positive development both in the horizontal and vertical basal relation of the
      jaw with a significant increase in mandibular length and in anterior lower facial
      height. On the other hand the class II,2 cases exhibited significantly reduced
      lower facial height, which can probably be considered to be a causal factor in
      the 70% relapse rate after completion of orthodontic treatment. In class III
      malocclusions the horizontal jaw relationship was stabilized throughout the
      orthodontic treatment period, however, following treatment a progressive
      alteration became apparent. The results achieved in this study add weight to the
      importance of taking skeletal maturation factors into consideration in patients
      with skeletal jaw discrepancies. These factors are useful in prognosticating the
      therapeutical goal to be achieved, the degree of stability during treatment, and
      the chances of relapse following treatment.

PMID- 7737616
TI  - [Individual prophylaxis against NSAID ulcers?].

PMID- 7737615
TI  - [The edge-centroid relation and overbite in Class-II.1 patients. A follow-up
      study].
AB  - This follow-up study evaluates lateral skull radiographs and jaw casts taken
      prior to treatment, at the end of treatment, and after a control period of one at
      a minimum of 25 orthodontically treated children, 14 males and 11 females, who
      had an Angle class II, 1 malocclusion and a deep overbite with the lower incisors
      impinging upon the palatal gingiva. The study's object of interest was the
      anterior-posterior relationship of the lower incisor edge to the upper incisor
      root centroid (i.e., the "edge-centroid relationship", Houston [7]). Its intent
      was to evaluate the correlation between edge-centroid relationship and an
      overbite relapse respectively when viewed in relation to the developments which
      take place in the dental and skeletal variables during the course of overbite
      reduction. The edge-centroid relationship was found, to present an interesting
      screening method in diagnosing class II, 1 cases, and, although with some
      reservations, the relationship is also useful in planning treatment.

PMID- 7737617
TI  - [Calcium antagonists also after myocardial infarction?].

PMID- 7737618
TI  - [What is the connection between Helicobacter pylori and dyspepsia?].

PMID- 7737619
TI  - [Ambulatory neuropsychological rehabilitation. More successful adaptation to
      private and professional milieu].

PMID- 7737620
TI  - [Laboratory diagnosis of HIV infection].
AB  - Recent use of modern methods in the field of molecular biology has provided new
      insights into the genetic and structural nature of HIV, which are now
      increasingly being applied to the diagnostic work-up. For the reliable laboratory
      diagnosis of HIV infection, three different possibilities are available:
      detection of specific antibodies against viral proteins (anti HIV AB), detection
      of the virus itself (HIV antigen) and detection of viral nucleic acid using in
      vitro amplification techniques. In this overview, we compare clinical and
      diagnostic parameters of an HIV infection, and discuss the current state of the
      art of an HIV infection and the future prospects offered by new molecular
      biological methods such as the use of recombinant antigens or the polymerase
      chain reaction (PCR) for the detection of viral nucleic acid.

PMID- 7737621
TI  - [Transsexualism--an extreme form of sexual identity disorder].
AB  - Transsexualism is the most extreme form of disturbed sexual identity. The
      sufferer identifies him or herself completely with the opposite sex. In many
      cases, the delusional and painful urge to belong to the opposite sex is so
      pronounced that the sufferer is at risk from autoaggressive and suicidal
      activity. Stimulated and supported by the possibilities offered by modern medical
      technical advances, most transsexuals now seek a sex change by means of hormonal
      and surgical treatment. Patient satisfaction after the complicated, high-risk and
      irreversible procedure of sex change treatment is variously assessed. Recently,
      there have been reports on successful psychotherapeutic treatment of transsexuals
      resulting in the preservation of the biologically given sex. In the present
      article, attention is drawn to the sociocultural change in transsexualism
      throughout the course of history, to the hypotheses resulting from research into
      causes, and to diagnostic criteria and therapeutic approaches.

PMID- 7737622
TI  - [Caries prevention using fluoridation--current status].

PMID- 7737623
TI  - [Acute poisoning. 2: First aid therapeutic measures].

PMID- 7737624
TI  - [Sleep-wake rhythm disorders in the framework of a Diogenes syndrome. Improvement
      in sleep architecture using supportive treatment with zolpidem].
AB  - In a 72-year-old man suffering from the Diogenes syndrome, but with no other
      pathologies (no dementia, no underlying depression), marked disorders in the
      sleep-wake rhythm developed. Treatment with zolpidem brought about an improvement
      in the sleep architecture. Psychotherapy, largely behavioral treatment, resulted
      in partial reintegration of the patient.

PMID- 7737625
TI  - [Thyroid function breaks down in mutation of the TSH receptors].

PMID- 7737626
TI  - Permissiveness of Kupffer cells for simian immunodeficiency virus (SIV) and
      morphological changes in the liver of rhesus monkeys at different periods of SIV
      infection.
AB  - The pathogenesis of liver injury, which remains unclear in the course of human
      immunodeficiency virus infection, can be investigated in simian immunodeficiency
      virus-infected macaques, which develop an immunodeficiency disease resembling
      human acquired immune deficiency syndrome (AIDS). We studied the livers of 21
      monkeys infected with simian immunodeficiency virus (SIVmac251) for 4 days to 39
      months and detected viral antigens in Kupffer cells, macrophages, and lymphocytes
      in 65% of the livers tested. Virus-containing cells were present in 5 out of 9
      livers tested as early as 4 days postinoculation. The number of positive cells as
      well as their content in viral proteins substantially increased in sinusoidal
      cells with the progression of the disease. Morphological features and double
      immunolabeling indicated that Kupffer cells constituted the predominant cell type
      containing viral antigens. The presence of multinucleated giant cells displaying
      the ultrastructural features of resident liver macrophages was another sign of
      the productive infection of Kupffer cells in vivo, which was attested by the
      observation of budding, immature, and mature SIV particles. Kupffer cell
      hyperplasia and hypertrophy were evident and appeared to be related to the
      development of SIV infection, because a close correlation was found between
      antigenemia and the surface area occupied by these cells. The Kupffer cells
      contained apoptotic lymphocytes, indicating that resident liver macrophages could
      play a role in the uptake of such cells from the blood. The production of tumor
      necrosis factor alpha (TNF alpha) and, possibly, interferon-alpha by Kupffer
      cells, the expression of vascular adhesion molecule-1, (VCAM-1), intralobular and
      periportal inflammation, and the proliferation and expansion of bile duct cells
      were other signs of liver involvement in SIV infection.

PMID- 7737627
TI  - The prevalence and spectrum of colonic lesions in patients with cirrhotic and
      noncirrhotic portal hypertension.
AB  - Portal hypertension diffusely affects the gastrointestinal tract. The frequency
      and profile of distinct colonic mucosal lesions (portal colopathy) and rectal
      varices (RV; veins > 4 cm above the anal verge) is not well studied. Fifty
      consecutive patients with portal hypertension (25 with cirrhosis, 10 with
      noncirrhotic portal fibrosis [NCPF], and 15 with extrahepatic portal vein
      obstruction [EHPVO]) were assessed clinically and by upper and lower
      gastrointestinal (GI) endoscopy. Colorectal lesions were seen in 35 (70%)
      patients, significantly more often in bleeders than in nonbleeders. Rectal
      varices were detected in 22 (44%) patients; larger and more often seen in EHPVO
      (80%) than in cirrhosis (28%) and NCPF (30%) (P < .01) patients. Portal colopathy
      was seen in 26 (52%) patients, with nearly similar frequency in cirrhotics, NCPF,
      and EHPVO patients. Previous sclerotherapy or presence of gastric varices had
      little influence on the development of these lesions. An association (P < .01)
      was, however, seen between the presence of colopathy and portal gastropathy.
      Overt bleeding was seen in 8% and 4% of patients with RV and colopathy,
      respectively. In conclusion, our results demonstrate that colorectal lesions are
      present in about two thirds of patients with portal hypertension. Patients with
      portal hypertension and lower GI bleeding should be colonoscoped. Patients with
      extrahepatic portal vein obstruction may in turn benefit from baseline
      sigmoidoscopic examination to define the presence and size of rectal varices.

PMID- 7737628
TI  - Role of thrombosis in the pathogenesis of congestive hepatic fibrosis (cardiac
      cirrhosis).
AB  - The pathogenesis of congestive cirrhosis is generally thought to be a reaction of
      the hepatic stroma to hypoxia, pressure, or necrosis. This does not explain the
      poor correlation between symptoms and severity of fibrosis and the irregular
      distribution of fibrosis within the liver. We have observed healed hepatic vein
      (HV) thrombosis in patients with congestive heart failure (CHF). The purposes of
      this study were to document hepatic vascular lesions in autopsy livers of
      patients with chronic CHF, to determine the role of these lesions in the
      pathogenesis of congestive cirrhosis, and to refine the definition of congestive
      cirrhosis. Twenty-five livers were studied, 13 with multiple large blocks 4 x 5
      cm. Sections were graded for parenchymal fibrous septa, sinusoidal fibrosis, and
      intimal fibrosis of portal veins (PVs) and HVs. Fibrous septa were found in
      livers of 7 of 13 patients with CHF and in none of 12 controls without CHF (P =
      .007). Parenchymal fibrosis was highly variable in distribution, often with
      severe septation in some areas and nearly normal morphology in others. Intimal
      fibrosis and obstruction of small- and medium-HVs were found only in livers of
      patients with CHF. The vascular lesions were confined to regions with fibrous
      septation and had morphology suggestive of organized thrombosis. Acute thrombi in
      sinusoids were noted in livers of 4 patients with CHF and in livers of 2 patients
      without CHF. These findings support the hypothesis that congestive cirrhosis is a
      response to intrahepatic thrombosis. The pattern of disease suggests that
      thrombus begins in sinusoids, occasionally propagates to HVs, and causes
      secondary local PV thrombosis, ischemia, parenchymal extinction, and fibrosis.

PMID- 7737629
TI  - Hepatic and portal vein thrombosis in cirrhosis: possible role in development of
      parenchymal extinction and portal hypertension.
AB  - Obliterative lesions in portal veins (PVs) and hepatic veins (HVs) of all sizes
      are known to occur in cirrhotic livers. PV lesions have generally been attributed
      to thrombosis, but the pathogenesis of the HV (veno-occlusive) lesions is
      unknown. We have studied 61 cirrhotic livers removed at transplantation to
      clarify the prevalence, distribution, and pathogenesis of venous lesions, as well
      as the association of these lesions with other morphological features and
      clinical morbidity. Intimal fibrosis that is highly suggestive of healed HV or PV
      thrombosis was found in at least 70% and 36% of livers, respectively. The
      distribution of HV lesions was patchy and largely confined to veins between 0.1
      and 3 mm in diameter, suggesting multifocal origin in small veins. PV lesions
      were more uniform throughout the liver, suggesting origin in large veins with
      propagation to the small veins. HV lesions were associated with regions of
      confluent fibrosis (focal parenchymal extinction), and PV lesions were associated
      with regional variation in the size of cirrhotic nodules and a history of
      bleeding varices. These observations suggest that thrombosis of medium and large
      PVs and HVs is a frequent occurrence in cirrhosis, and that these events are
      important in causing progression of cirrhosis.

PMID- 7737630
TI  - Effects of hepatocyte growth factor on the growth and metabolism of human
      hepatocytes in primary culture.
AB  - The effect of recombinant human hepatocyte growth factor (h-rHGF), a potent
      mitogen for hepatocytes, was investigated in primary cultures of human
      hepatocytes. Here, we describe a series of experiments to investigate the
      kinetics of its mitogenic action, as well as its metabolic effects on cultured
      human hepatocytes. The h-rHGF is a potent signal for initiating DNA synthesis in
      human hepatocytes, with maximal stimulatory effects at 10 ng/mL (0.1 pmol/L). The
      kinetics of DNA synthesis showed a lag of about 48 to 72 hours, followed by a
      maximum at 96 hours. At least 48 hours of continuous exposure to h-rHGF are
      required to initiate DNA synthesis in quiescent human hepatocytes. Cell cycle
      analysis by flow cytometry showed that most of quiescent 2c cells have left G0/G1
      and entered the cell cycle (S and G2/M phases) by 96 hours of continuous exposure
      to h-rHGF. When compared with other growth factors, h-rHGF was a much more potent
      mitogen. The effects of 10 ng/mL (0.1 pmol/L) h-rHGF on DNA synthesis were only
      achieved by 1.5 pmol/L epidermal growth factor (EGF), 0.1 mumol/L insulin, or 1
      mumol/L glucagon. It is noteworthy that the effect of h-rHGF was potentiated by
      glucagon but not by insulin or EGF. The stimulatory effect of HGF on DNA
      synthesis was gradually inhibited by h-rHGF transforming growth factor beta (TGF
      beta) in the range 1 to 10 ng/ml. The HGF also influenced the expression of other
      hepatic genes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737631
TI  - Cardiovascular effects of octreotide in patients with hepatic cirrhosis.
AB  - Octreotide is thought to reduce splanchnic and variceal blood flow with minimal
      effects on the systemic circulation in cirrhotic patients with portal
      hypertension. However, we noticed significant bradycardia in some patients
      immediately after administration of bolus doses of octreotide. Therefore, we
      investigated the effect of intravenous octreotide on systemic hemodynamics in 59
      patients with cirrhosis. In two double-blind, placebo-controlled protocols, 32
      patients received a 25-micrograms bolus and 20 patients received an infusion of
      50-micrograms/hr of octreotide/placebo. Immediately after the bolus dose of
      octreotide was administered, there were significant reductions in pulse rate (77
      +/- 3 vs. 65 +/- 3 beats per minute, P < .01) and cardiac output (9.2 +/- 0.8 vs.
      7.9 +/- 0.8 L/min; P < .01) and significant increases in mean arterial pressure
      (81 +/- 3 vs. 87 +/- 3 mm Hg; P < .05), mean pulmonary artery pressure (9.1 +/-
      1.0 vs. 16.6 +/- 1.5 mm Hg; P < .01), right atrial pressure (3.8 +/- 0.8 vs. 6.6
      +/- 1.0 mm Hg; P < .01), right ventricular pressure (7.1 +/- 0.6 vs. 12.5 +/- 1.3
      mm Hg; P < .01), pulmonary capillary wedge pressure (4.8 +/- 0.8 vs. 11.2 +/- 1.4
      mm Hg; P < .01), systemic vascular resistance, and pulmonary vascular resistance.
      Thirty minutes after the start of the infusion, there were significant increases
      in mean right atrial pressure, right ventricular pressure, pulmonary artery
      pressure, and pulmonary capillary wedge pressure. This study suggests that
      intravenous octreotide has significant effects on the systemic circulation in
      patients with cirrhosis and that these effects appear to be more marked after
      administration of bolus doses.

PMID- 7737632
TI  - Serum cholestanol, cholesterol precursors, and plant sterols during placebo
      controlled treatment of primary biliary cirrhosis with ursodeoxycholic acid or
      colchicine.
AB  - A randomized placebo-controlled 2-year study was performed in 69 patients with
      primary biliary cirrhosis (PBC) on serum lipids during ursodeoxycholic acid
      (URSO) and colchicine treatments. In addition to serum bilirubin and alkaline
      phosphatase (AFOS), two variables considered to reflect liver function, serum
      lipoproteins, cholesterol precursors (squalene, delta 8-cholestenol, lathosterol
      and desmosterol), markers of cholesterol synthesis, cholestanol and plant sterols
      (campesterol and sitosterol), markers of liver function and cholesterol
      absorption, were studied before and during the treatments. Serum bilirubin was
      inconsistently improved by URSO, whereas improvement of AFOS values was better by
      URSO than colchicine, especially in patients with initially more advanced PBC.
      Serum total cholesterol was reduced by both drugs, very low-density lipoprotein
      (VLDL) and high-density lipoprotein (HDL) cholesterol by URSO. Cholesterol
      precursor sterols were increased by both URSO and colchicine mainly in patients
      with initially less severe PBC. On the other hand, the cholestanol values were
      markedly increased initially, and the values were related to bilirubin during the
      2-year period, were further increased in the placebo group, and reduced in the
      URSO and colchicine groups, so that the improvement was highest in the URSO
      treated patients with the severe form of PBC. The increase of the serum plant
      sterols, particularly that of sitosterol, was retarded by the two drugs so that
      the campesterol/sitosterol ratio, which was related to serum bilirubin, was
      increased especially in the cases with initially more advanced PBC.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7737633
TI  - Cholesterol metabolism in liver and gallbladder mucosa of patients with
      cholesterolosis.
AB  - The objective of this study was to investigate possible pathogenetic factors for
      cholesterolosis. Liver tissue, gallbladder mucosa, and gallbladder bile were
      collected in patients with cholesterol gallstones (GS) (14 patients with and 14
      patients without cholesterolosis) and gallstone-free (GSF) subjects (11 with and
      21 without cholesterolosis) undergoing cholecystectomy. In cholesterolosis, the
      gallbladder mucosa was characterized by a fivefold increase in esterified
      cholesterol and normal content of free cholesterol. The hepatic levels of 3
      hydroxy-3-methylglutaryl coenzyme A reductase activity, governing cholesterol
      synthesis, and acyl coenzyme A: acyltransferase activity, catalyzing the
      esterification of cholesterol, were similar in patients with and without
      cholesterolosis. Also in the gallbladder mucosa, the 3-hydroxy-3-methylglutaryl
      coenzyme A reductase activity was similar in patients with and without
      cholesterolosis. The acyl coenzyme A: acyltransferase activity of the gallbladder
      mucosa was increased in the GSF subjects with cholesterolosis. The nucleation
      time of gallbladder bile was shorter in the GSF subjects with cholesterolosis
      compared with the time of those without cholesterolosis. Occurrence of
      cholesterol crystals, lipid composition, and cholesterol saturation of
      gallbladder bile were not significantly influenced by the absence or presence of
      cholesterolosis. The study has confirmed that cholesterolosis is associated with
      a several-fold increased level of esterified cholesterol. The data suggest that
      patients with cholesterolosis have normal hepatic cholesterol formation and
      esterification. The local synthesis of cholesterol in the gallbladder mucosa
      seems to be normal. A positive correlation was obtained between the cholesterol
      saturation of bile and the content of esterified cholesterol in the gallbladder
      mucosa in the whole series of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737634
TI  - Increase of deoxycholate in supersaturated bile of patients with cholesterol
      gallstone disease and its correlation with de novo syntheses of cholesterol and
      bile acids in liver, gallbladder emptying, and small intestinal transit.
AB  - A total of 100 nonobese and normolipidemic subjects (29 control subjects, 49
      patients with cholesterol stones [CSs], and 22 patients with brown pigment
      stones) were studied to elucidate the pathogenetic contributions of deoxycholate
      (DC) to supersaturated bile formation with special reference to de novo syntheses
      of cholesterol and bile acids in the liver. A higher proportion of DC was
      observed in gallbladder bile from patients with CSs (CSs; 21.7 +/- 1.4%, mean +/-
      SEM, vs. control subjects; 10.2 +/- 0.9%). Cholesterol saturation in bile was
      elevated parallel to the increase of DC (r = .48; P = .0002), irrespective of the
      existence of stones. In a comparison between the 52 subjects with increased DC in
      bile (> 10% of biliary bile acids) and the 20 subjects without the increase (<
      10%), the molar percentage of cholesterol in bile was significantly higher in the
      former (9.4 +/- 0.5%) than in the latter (6.7 +/- 0.4%) (P < .001). Consistent
      with the decrease in steady-state level of low-density lipoprotein (LDL) receptor
      messenger RNA (mRNA), the catalytic activity and mRNA level of microsomal hepatic
      3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting
      enzyme for de novo cholesterol synthesis, were significantly lower in the former
      (2.9 +/- 0.3 pmol/min/mg protein) than in the latter (5.1 +/- 0.6) (P < .0001).
      Biliary molar percentage of bile acids was significantly lower in the former
      (69.8 +/- 1.1%) than in the latter (75.2 +/- 1.5%) (P < .01). However, contrary
      to expectations, the catalytic activity and mRNA level of cholesterol 7 alpha
      hydroxylase, the rate-limiting enzyme for bile acid synthesis, were significantly
      higher in the former (5.8 +/- 0.4 pmol/min/mg protein) than in the latter (3.7 +/
      0.6) (P < .01). The magnitude of the impaired gallbladder emptying (control
      subjects; 78.4 +/- 4% vs. CSs; 58 +/- 3%; P < .0005) together with the prolonged
      small intestinal transit (control subjects; 126 +/- 9 minutes vs. CSs; 198 +/- 9
      minutes; P < .01) correlated significantly with the increased percentage of DC in
      bile. It is concluded that in cholesterol gallstone disease an increase of DC in
      bile, linked to an impaired gallbladder emptying together with a prolonged small
      intestinal transit, may play a significant role in downregulating de novo
      cholesterol synthesis but not bile acid synthesis in the liver.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7737635
TI  - Diagnostic value of fine-needle puncture of the gallbladder: side effects,
      safety, and prognostic value.
AB  - Bile sampling without the risk of contamination by pancreatic and duodenal
      secretions and avoiding unpredictable influences of general anesthesia during
      biliary surgery on biliary analytics are feasible with percutaneous puncture of
      the gallbladder. In 207 patients with gallstones, gallbladder puncture was
      performed under local anesthesia with a 22-gauge spinal needle under continuous
      real-time ultrasound guidance. Bile samples were investigated for biliary lipids
      and nucleation time. Complete aspiration of gallbladder bile could be achieved in
      all patients without complications such as bleeding, bile leak, or inflammation.
      Of these patients, 11.6% reported mild abdominal problems, 3.4% required
      analgetics, and in 1.0% biliary colics were observed. Elective cholecystectomy
      was performed in 1 patient. Of the bile samples, 10.1% were contaminated with
      bactobilia. Biliary lipids, cholesterol saturation index (CSI), total lipid
      concentration (TLC), and bacteriological contamination were independent of
      gallstone number, whereas patients with solitary gallbladder stones exhibited a
      significantly longer nucleation time (NT) in comparison with those with multiple
      stones. In patients with gallstones, fine-needle puncture of the gallbladder
      represents an important diagnostic procedure and can be performed within minutes
      without major side effects if performed by an experienced sonographer.

PMID- 7737636
TI  - Kupffer cell iron overload induces intercellular adhesion molecule-1 expression
      on hepatocytes in genetic hemochromatosis.
AB  - The mechanisms underlying iron-induced liver fibrogenesis in patients with
      genetic hemochromatosis are poorly understood. We studied signs of Kupffer cell
      activation and inflammatory responses in liver biopsy specimens obtained from 15
      patients with untreated and six patients with treated hemochromatosis.
      Immunohistochemistry was performed on 11 of the untreated and all treated
      patients. Three of the untreated patients (20%) had cirrhosis and eight (53%) had
      fibrosis. None had chronic active hepatitis (CAH). Immunohistochemistry indicated
      that 55% of the untreated patients had sparse intercellular adhesion molecule-1
      (ICAM-1) expression by hepatocytes, and all of these had Kupffer cell iron
      overload. No ICAM-1 expression was seen by hepatocytes in treated patients or
      healthy controls. ICAM-1 was strongly expressed by hepatocytes from control
      patients with inflammatory liver disease. HLA-DR reactivity was seen on
      sinusoidal cells in all groups, but not on hepatocytes except for two of the
      control patients with CAH. Twenty-seven percent of the untreated hemochromatosis
      patients displayed moderate infiltration by CD3-positive lymphocytes. Electron
      microscopy of samples from untreated hemochromatosis patients showed hypertrophic
      Kupffer cells containing iron-rich remnants of phagocytosed hepatocytes. Fat
      storing cells close to iron-laden hepatocytes contained multiple lipid droplets
      and adjacent collagen fibril bundles. Thus, in patients with untreated genetic
      hemochromatosis and Kupffer cell iron overload, hepatocytes occasionally express
      ICAM-1. In regions with heavy iron overload, Kupffer cell hypertrophy and
      transition of fat-storing cells are seen. Our findings indicate that release of
      factors from iron-loaded, activated Kupffer cells is of importance for the
      transformation of fat-storing cells and increased collagen deposition seen in
      genetic hemochromatosis.

PMID- 7737637
TI  - Calculation of child and adult standard liver volume for liver transplantation.
AB  - Despite refinements in surgical techniques for liver transplantation, liver size
      disparity remains one of the most common problems in pediatric patients. Optimal
      liver graft size remains unknown and the volume of diseased liver in the
      recipient is not indicative of the volume (standard liver volume [LV]) optimal
      for the recipient's metabolic demands. To establish a formula for calculating the
      standard LV in the pediatric and adult populations for liver transplantation,
      whole LVs were measured using computed tomography (CT) in 96 patients (65
      pediatric and 31 adolescent or adult subjects) with normal liver whose disease
      conditions did not seem to affect body weight (BW) or LV. In the 96 subjects, the
      ratio of estimated LV to BW decreased gradually as age increased until
      approximately 16 years, when it started to level off. On the other hand, there
      seemed to be a directly proportional relationship between the estimated LV in
      vivo and body surface area (BSA) (r = .981; r2 = .962; P < .0001) in the subjects
      as a whole, and the formula, LV (mL) = 706.2 x BSA (m2) + 2.4, was established
      from the measured data by simple regression analysis. Another predicting
      equation, LV (mL) = 2.223 x BW (kg)0.426 x body height (BH) (cm)0.682, was
      produced by multiple regression analysis (r2 = .969; P < .0001). Considering its
      simplicity of use, we adopted the first formula for predicting standard LV in an
      individual patient.

PMID- 7737638
TI  - Sclerotherapy plus octreotide versus sclerotherapy alone in the prevention of
      early rebleeding from esophageal varices: a randomized, double-blind, placebo
      controlled, multicenter trial. New Italian Endoscopic Club.
AB  - Because of its ability to decrease portal pressure, azygos blood flow, and
      postprandial splanchnic hyperemia, octreotide administration could be effective
      in reducing early rebleeding in patients undergoing endoscopic variceal
      sclerotherapy (EVS). We report the results of a trial comparing EVS + octreotide
      versus EVS alone. Consecutive patients with cirrhosis and endoscopically proven
      variceal hemorrhage were considered eligible for the trial if hemodynamically
      stable for at least 24 hours after bleeding stopped. Patients with advanced liver
      cancer or having received EVS treatment in the past were not enrolled. After
      enrollment patients were submitted to EVS (day 1); all patients were randomized
      to receive octreotide, 100 micrograms three times a day subcutaneously, or an
      identical placebo, up to day 29; EVS was repeated at days 8, 15, and 29. Fifty
      eight patients were randomized to receive either EVS + octreotide (n = 26) or EVS
      alone (n = 32). The two groups were evenly balanced for sex, age, Child-Pugh
      class, history of previous bleeding, endoscopic appearance of varices, or
      treatment received in emergency. Eight of 26 (31%) patients in the EVS +
      octreotide group rebled, compared with 11 of 32 (34%) in the EVS group. Four of
      the eight (50%) patients in the former group and 8 of 11 (73%) in the latter,
      respectively, bled within day 15. There were 10 (38.5%) deaths in the EVS +
      octreotide group (seven bleeding-related), compared with seven (21.9%) (five
      bleeding-related) in the EVS group; these differences did not reach statistical
      significance. Administration of octreotide, 100 micrograms three times a day,
      subcutaneously, to patients undergoing EVS for prevention of recurrent variceal
      bleeding does not decrease the incidence of early rebleeding.

PMID- 7737639
TI  - Bacterial and fungal infections after liver transplantation: an analysis of 284
      patients.
AB  - A prospective study of bacterial and fungal infections after liver
      transplantation in 284 adults was undertaken. One hundred seventy-five (62%)
      became infected; bacterial or fungal infections occurred in 159 (56%) and 36
      (13%) patients, respectively. Gram-positive cocci, in particular Staphylococcus
      aureus and Enterococcus faecium, were the commonest bacterial pathogens, and
      bacteremia and wound infection were the most frequent bacterial infections. Acute
      rejection and prolonged admission were independent risk factors for bacterial
      infection; pretransplantation antibacterials had a protective effect. Fungal
      infection most frequently involved the urinary tract and chest; Candida albicans
      was the most common pathogen. Four independent variables predicted fungal
      infection: low pretransplantation hemoglobin, high pretransplantation bilirubin,
      return to surgery, and prolonged therapy with ciprofloxacin. Patients with acute
      liver failure were more prone to bacterial, but not fungal, infection. No
      associations were found between infections and duration of surgery. Bacterial,
      and to a lesser extent, fungal infections are important complications of liver
      transplantation. However, liver transplantation surgery per se may not be the
      major determinant of infection.

PMID- 7737640
TI  - Which is the best surgery for Budd-Chiari syndrome: venous decompression or liver
      transplantation? A single-center experience with 50 patients.
AB  - The optimal treatment of Budd-Chiari syndrome (BCS) remains an open question. It
      is still a matter of controversial discussion whether venous decompression or
      liver transplantation is superior. To elucidate the role and prognosis of both
      surgical options in our own experience, a consecutive series of 50 patients
      treated between 1981 and 1993 was retrospectively analyzed. Twelve patients had
      different types of portosystemic shunts or local decompressive procedures, and
      transplantation was performed in 43 cases, including five with previous
      conventional surgery. The overall mortality of 18 of 50 was conventional surgery.
      The overall mortality of 18 of 50 was concentrated within the early postoperative
      period, with no patient lost after 1 year. In the venous decompression group, the
      success rate was only 29%, and treatment failure was closely related to the
      finding of cirrhosis or technical problems like vascular thrombosis. After
      transplantation, early complications were rejection, primary nonfunction, or
      graft necrosis, and contributed significantly to the risk of sepsis. Thirty of 43
      liver recipients are currently alive, including four rescued after failed
      decompressive surgery, with 1- and 10-year survival of 69%, and excellent
      recurrence-free rehabilitation. These results clearly indicate that patient
      selection plays a dominant prognostic role in the treatment of BCS. Venous
      decompression and liver transplantation should both be integrated in a common
      therapeutic concept, and the individual decision for the preferred approach must
      be based on the leading clinical symptom: portal hypertension or liver failure,
      together with the assessment of reversibility of hepatic damage, and the
      potential of cure of the underlying disease.

PMID- 7737641
TI  - Immunoglobulin G lymphocytotoxic antibodies in clinical liver transplantation:
      studies toward further defining their significance.
AB  - Twenty-two consecutive liver allograft recipients, who tested positive for
      immunoglobulin G (IgG) lymphocytotoxicity were subjected to pretransplantation
      and posttransplantation immunologic monitoring of anti-donor IgG lymphocytotoxic
      antibody titers, total hemolytic complement activity (CH100), circulating immune
      complexes (CIC), and platelet counts in an effort to improve our understanding of
      the preformed antibody state in clinical hepatic transplantation. Ten
      contemporaneous liver transplant recipients whose crossmatch results were
      negative and who experienced severe hepatocellular damage early after
      transplantation were included as controls. Crossmatch test results were negative
      1 day after transplantation and during the 1 month follow-up remained negative in
      14 of 22 (64%) sensitized recipients, most of whom had relatively low (< or =
      1:16) anti-donor IgG antibody titers before transplantation. After
      transplantation, this group and the control group experienced no
      thrombocytopenia, no increase of CIC, and a gradual increase in CH100 activity
      that reached normal levels within 1 week. A strong negative correlation between
      prothrombin time (PT) and CH100 activity in these groups of patients suggested
      that changes in CH100 activity (P < .0005) were tightly linked to liver synthetic
      function. In contrast, the crossmatch test results remained positive after
      transplantation in 8 of 22 (36%) sensitized recipients, all of whom had
      relatively high (> 1:32 to 1024) pretransplantation titers of anti-donor IgG
      antibodies. After transplantation these patients developed a syndrome that was
      characterized by decreased CH100 activity and increased CIC compared with
      pretransplantation levels and refractory thrombocytopenia that was associated
      with a 50% allograft failure rate because of biopsy-proven humoral and acute
      (cellular) rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737642
TI  - Regression of bile duct damage and bile duct proliferation in the non
      rearterialized transplanted rat liver is associated with spontaneous graft
      rearterialization.
AB  - The aim of this study was to investigate the long-term consequences of non
      rearterialization of the graft in rat liver transplantation. Liver
      transplantation with (AOLT) and without graft rearterialization (NOLT) was
      performed in anesthetized male Lewis rats. Quantitative morphometry and
      semiquantitative histopathology of the liver were performed at various times
      after operation. Volume fractions of tissue components were determined. The
      number of arteries and bile ducts per portal tract were measured in histological
      sections from both groups. Hepatic blood flow was measured using the radioactive
      microsphere technique in rats after NOLT (6 months). AOLT livers had a preserved
      lobular architecture at all time points and unaltered volume fractions. In
      addition, AOLT livers maintained approximately one artery and one bile duct per
      portal tract after transplantation. NOLT livers showed bile duct damage at 3
      days, cellular infiltration and ductular proliferation at 1 week, increased
      ductular proliferation at 4 weeks, and fibrosis at 6 months. The volume fractions
      for nonhepatocyte parenchyma (3 days, 19.14 +/- 1.29; 1 week, 20.44 +/- 1.76; 4
      weeks, 15.46 +/- 3.14), bile ducts/ductules (1 week, 4.88 +/- 1.07; 4 weeks, 7.20
      +/- 2.42), and connective tissue (4 weeks, 4.02 +/- 1.66; 6 months, 14.94 +/-
      0.63) were significantly increased. Hepatocyte volume fraction was significantly
      decreased at all time points. A total of 1.58 +/- 0.08 arteries/portal tract were
      found in NOLT livers after 4 weeks, rising to 2.44 +/- 0.10 arteries/portal tract
      after 6 months. At 6 months, hepatic arterial blood flow (0.69 mL/min/g) was
      significantly higher (P < .02) than control (0.25 mL/min/g).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7737643
TI  - Progression of subcellular changes during chemical hypoxia to cultured rat
      hepatocytes: a laser scanning confocal microscopic study.
AB  - The aim of this study was to evaluate changes in the subcellular organelles of
      cultured hepatocytes by laser scanning confocal microscopy during chemical
      hypoxia with cyanide and iodoacetate, inhibitors of mitochondrial respiration and
      glycolysis, respectively. Parameter-specific fluorophores used were calcein for
      cell topography and membrane permeability, rhodamine-dextran for lysosomes,
      rhodamine 123 and tetramethylrhodamine methylester (TMRM) for mitochondrial
      membrane potential (delta psi) and propidium iodide for loss of cell viability.
      During the first 30 to 40 minutes of chemical hypoxia to cultured hepatocytes,
      numerous surface blebs formed and cell volume increased, but delta psi decreased
      relatively little. Subsequently, the nonspecific permeability of mitochondrial
      membranes increased, and mitochondria depolarized. These events were followed a
      few minutes later by disintegration of individual lysosomes. After a few more
      minutes, viability was lost as indicated by bleb rupture, gross plasma membrane
      permeability to calcein, and nuclear labeling with propidium iodide. Thus, the
      following sequence of intracellular events occurred during chemical hypoxia:
      adenosine triphosphate (ATP) depletion, bleb formation with cellular swelling,
      onset of a mitochondrial permeability transition, disintegration of lysosomes,
      plasma membrane failure from bleb rupture, and cell death. Any explanation of the
      pathophysiology of hypoxic injury must take into account this unique sequence of
      events.

PMID- 7737644
TI  - Is dietary erucic acid hepatotoxic in pregnancy? An experimental study in rats
      and hamsters.
AB  - The hypothesis that dietary erucic acid may contribute to the pathogenesis of
      intrahepatic cholestasis of pregnancy has been examined in pregnant rats and
      hamsters after prolonged feeding of diets containing 25% rapeseed oil rich in
      erucic acid (40% of fatty acids) or corn oil, without erucic acid. Both dietary
      oils were well tolerated, although weight gain was 17% to 20% less in animals
      receiving rapeseed oil. Rats and hamsters were studied on the last day of
      pregnancy and compared with age- and diet-matched nonpregnant animals.
      Histological examination showed no major morphologic abnormalities in liver,
      heart, kidneys, and adrenals. Similar microscopic deposits of fat were found in
      the livers and hearts of pregnant hamsters of both dietary groups.
      Chromatographic analysis of fatty acids in liver, heart, and kidney homogenates
      of hamsters and in isolated rat liver cells reflected the fatty acid composition
      of the dietary oils: oleic (18:1) and linoleic (18:2) acids were among the
      predominant fatty acids. Erucic acid was found in a higher proportion in the
      heart (14% by weight of total fatty acids) than in the liver (3%) and kidneys
      (3%) of animals fed rapeseed oil. Bile flow and biliary lipid composition was
      similar in rats and hamsters fed rapeseed or corn oil. Bile flow tended to be
      less in pregnant than in nonpregnant animals. Pregnant hamsters fed rapeseed oil
      tended to have the lowest bile flow. The lithogenic index of bile was slightly
      decreased in pregnant rats and increased in pregnant hamsters, although these
      proportional changes were similar for both diets. In all circumstances the
      lithogenic index remained below a value of 1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737645
TI  - Alterations in bile ducts and peribiliary microcirculation in rats after common
      bile duct ligation.
AB  - The chronological changes in ductular epithelium and peribiliary capillary
      plexuses (PBPs) after bile duct ligation are not well understood. Therefore, we
      examined alterations in both intrahepatic bile ductules and peribiliary
      microcirculation in rats after ligation of the common bile duct using
      immunohistochemistry, transmission electron microscopes (TEM), and scanning
      electron microscopes (SEM). Ductular proliferations appeared first in the
      peripheral areas of the portal spaces and then gradually advanced along with
      increasing jaundice. Distorted configuration of the hepatic parenchyma with
      interconnecting stroma rich in irregular ductules developed 4 weeks after the
      ligation. Numerous biliary cell types and cells of types intermediate between
      hepatocytes and biliary cells together with poorly fenestrated capillary-type
      vessels appeared in the periportal parenchyma, in association with an increased
      number of canalicular-ductular junctions on TEM. These biliary cells were often
      found within the lobules and apart from the stroma. SEM examination of hepatic
      microvascular casts using methacrylated resin showed formation of irregular
      portal and periportal capillary networks, partly derived from coarsened
      sinusoids. Direct connections between the newly formed capillary networks and the
      pre-existing PBPs or sinusoids were numerous, although there were few direct
      connections between the capillary networks and the hepatic arterial branches.
      Thus, these proliferated ductules and newly formed complicated capillary networks
      might play an important role in the effective transport of biliary materials
      between hepatocytes and native bile ducts or proliferated ductules through the
      altered microcirculation after bile duct ligation.

PMID- 7737646
TI  - Glutathione conjugation of bromosulfophthalein in relation to hepatic glutathione
      content in the rat in vivo and in the perfused rat liver.
AB  - The relation between the rate of glutathione (GSH) conjugation and hepatic GSH
      content was studied in the rat in vivo and the in situ single-pass-perfused rat
      liver preparation with bromosulfophthalein (BSP) as the model substrate. The
      biliary excretion of the BSP-GSH conjugate and the hepatic GSH content were
      monitored simultaneously during intravenous infusions with BSP in the rat in
      vivo, and during liver perfusions with BSP-containing perfusion medium. Rats were
      pretreated with single or multiple doses of buthionine sulfoximine, an inhibitor
      of the de novo synthesis of GSH. Surprisingly, the excretion of the BSP-GSH
      conjugate was sustained at a high rate, despite a virtually complete depletion of
      hepatic GSH, both in the rat in vivo as well as in the perfused rat liver. The
      results indicate that GSH was still available for conjugation with BSP after
      apparent depletion of the hepatic GSH pool, presumably because of a residual de
      novo synthesis of GSH in the liver. Despite the multiple pretreatment with
      buthionine sulfoximine, the de novo GSH synthesis was sufficient to sustain a
      high rate of GSH conjugation of BSP. The cosubstrate-Km for GSH conjugation of
      BSP in the liver was estimated to be very small (approximately 0.3 mumol/g): the
      excretion rate of the BSP-GSH conjugate was only impaired at minimal hepatic GSH
      levels.

PMID- 7737647
TI  - Different features of Ca2+ oscillations in differentiated and undifferentiated
      hepatocyte doublets.
AB  - Cytosolic free Ca2+ ([Ca2+]i) oscillations are postulated to play a critical role
      in cellular proliferation. By using doublets of normal rats (NR) and those 18
      hours after two-thirds hepatectomy (PHR), we investigated cytosolic free Ca2+
      ([Ca2+]i) responses in liver regeneration. Normal rat hepatocyte doublets that
      retain their bile canaliculi are polarized and well differentiated. PHR doublets,
      which also retain their bile canaliculi, were characterized as undifferentiated
      by (1) decreased canalicular secretion of fluorescein-isothiocyanate-labeled
      glycocholate; (2) increased labeling index of hepatocytes in BrdU staining
      (approximately 30%); and (3) impaired transfer of fluorescent dye injected into
      one cell of the pair to the other. Addition of phenylephrine to NR and PHR
      doublets in the presence of extracellular Ca2+ resulted in [Ca2+]i oscillations
      or a nonoscillatory-sustained increase in [Ca2+]i followed by a gradual return to
      the baseline. Extracellular Ca2+ was not required for [Ca2+]i oscillations but
      was necessary for a sustained increase in [Ca2+]i. Simultaneous addition of
      prazosin, alpha 1-receptor blocker, to doublets immediately abolished these
      [Ca2+]i responses. The [Ca2+]i level in each of the adjacent cells was
      synchronous in sustained increase in [Ca2+]i but asynchronous in [Ca2+]i
      oscillations. As the phenylephrine concentration was increased (1 to 100
      mumol/L), oscillations were replaced by a sustained increase in [Ca2+]i in NR
      doublets. In contrast, in PHR doublets, oscillations remained, whereas the
      frequency of oscillations increased in a dose-dependent manner. These results
      indicate that the mechanisms of phenylephrine-evoked [Ca2+]i responses are
      different in differentiated and undifferentiated doublets and that the frequency
      modulation of [Ca2+]i oscillations may be involved in the intracellular signal
      transduction in the cellular proliferation process during liver regeneration.

PMID- 7737648
TI  - Glucagon effect on intracellular proteolysis and pericanalicular location of
      hepatocyte lysosomes in isolated perfused guinea pig livers.
AB  - In guinea pigs, glucagon choleresis is accompanied by a significant, but
      transient, stimulation of biliary protein secretion, which can be accounted for
      mainly by biliary discharge of lysosomal enzymes. To clarify whether
      intracellular proteolysis--a process regulated by glucagon and taking place
      predominantly in the lysosomes--may interact with biliary protein secretion, we
      determined hepatic proteolytic activity and bile secretory function during
      substrate deprivation, amino acid supplementation, and glucagon administration in
      isolated perfused guinea pig livers. To further elucidate the nature of transient
      lysosomal enzyme release into bile during glucagon infusion, we analyzed
      pericanalicular distribution of lysosomes by quantitative electron microscopy.
      The results demonstrate that intracellular proteolysis is accompanied by biliary
      excretion of lysosomal enzymes. Glucagon-induced secretion of these enzymes as
      well as labeled proteins into bile occurs independent of protein breakdown and
      cannot be modulated by addition of amino acids as potent inhibitors of
      intracellular proteolysis. During glucagon administration, bile canalicular area
      and pericanalicular distribution of secondary lysosomes show a rapid increase,
      which persists during the entire infusion period and thus does not explain the
      transient biliary release of lysosomal enzymes. We therefore postulate that
      regulation of this process must be located beyond the lysosomal compartment,
      either involving transport processes or intracellular kinetics of lysosome
      formation or altered fusion kinetics at the bile canalicular membrane
      compartment. Metabolic and biliary effects of glucagon seem to occur independent
      of each other and to underly different regulatory mechanisms.

PMID- 7737649
TI  - Insulinlike growth factor-II/mannose 6-phosphate receptor is expressed on CCl4
      exposed rat fat-storing cells and facilitates activation of latent transforming
      growth factor-beta in cocultures with sinusoidal endothelial cells.
AB  - Transforming growth factor beta (TGF-beta), a potent fibrogenic cytokine, is
      secreted in latent form. We examined which cell type in both normal and carbon
      tetrachloride (CCl4)-induced fibrotic rat liver bears surface type II IGF/mannose
      6-phosphate (IGF-II/M6P) receptor, known to facilitate activation of TGF-beta. In
      addition, the role of the IGF-II/M6P receptor in activation of latent TGF-beta
      was investigated in a coculture system with sinusoidal endothelial cells.
      Northern hybridization analysis for IGF-II/M6P receptor messenger RNA (mRNA) was
      performed on total RNA of different isolated and purified liver cell types. In
      normal liver, cells expressed little IGF-II/M6P receptor mRNA. In fibrotic liver,
      we found significant expression only in fat-storing cells. The presence of IGF
      II/M6P receptors was established by [125I]IGF-II binding assays on freshly
      isolated fat-storing cells from normal and CCl4-exposed rat livers. We found
      specific binding of [125I]IGF-II only on CCl4 exposed fat-storing cells. As
      determined by polyacrylamide gel electrophoresis after affinity labeling, the
      specific binding involved 220 kD type II IGF receptors. Scatchard analysis
      revealed the presence of 3,043 +/- 1,378 IGF-II/M6P high-affinity receptors/fat
      storing cell, with a Kd of 387 = 165 pmol/L. With a mink lung epithelial cell
      (Mv1Lu) proliferation inhibition assay, inhibition of proliferation (a measure of
      active TGF-beta function) was determined using conditioned media of activated fat
      storing cells, cocultures of fat-storing cells, and endothelial cells and pure
      endothelial cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737650
TI  - Hepatic fibrosis produced in guinea pigs by chronic ethanol administration and
      immunization with acetaldehyde adducts.
AB  - Experimental hepatic fibrosis was produced in the guinea pig. We produced hepatic
      necrosis associated with inflammatory cell infiltration in guinea pigs immunized
      with acetaldehyde adducts and fed ethanol for 40 days. Extending the period of
      these treatments to 90 days resulted in producing hepatic fibrosis developing
      around individual hepatocytes in the terminal hepatic venule areas and portal
      areas, accompanied by an increase in hepatic hydroxyproline content. In contrast,
      no fibrosis was observed in the livers of the control groups that had been
      exposed to nothing, ethanol alone, or a combination of ethanol and immunization
      with unmodified human hemoglobin. Minimal fibrotic changes were observed in
      animals immunized with human hemoglobin acetaldehyde adducts but not fed ethanol.
      These results indicate that the formation of acetaldehyde adducts and the
      acquisition of immunity against them can produce hepatic fibrosis. Immune
      mechanisms against acetaldehyde adducts may, in part, be involved in the
      pathogenesis of hepatic fibrosis seen in alcoholics.

PMID- 7737651
TI  - Rapid activation of the Stat3 transcription complex in liver regeneration.
AB  - Liver regeneration in response to partial hepatectomy is a physiological growth
      response observed in the intact animal. Understanding the early signals that
      trigger liver regeneration is of vital importance to understand the liver's
      response to injury. It has been observed that several growth factors and
      cytokines, including epidermal growth factor (EGF) and interleukin-6 (IL-6), can
      activate members of the signal transducers and activators of transcription (Stat)
      family of transcription factors resulting in tyrosine phosphorylation of these
      factors, nuclear translocation, and an active DNA binding transcriptional
      complex. Because Stat3 participates in the regulation of primary growth response
      genes, we wondered if it is induced in the early phase of liver regeneration. We
      found that Stat3 DNA-binding activity is increased in the remnant liver within 30
      minutes of partial hepatectomy and peaks at more than 30-fold at 3 hours. This
      induction is not observed after sham surgery. The induction of Stat3 appears to
      be part of the initial response of the remnant liver to partial hepatectomy,
      because it occurs in the presence of cycloheximide-mediated protein synthesis
      blockade. Activation of Stat3 is unusual, because it extends beyond the immediate
      early time period and remains near peak level at 5 hours posthepatectomy.
      Although insulin-treated H35 cells activate many of the same immediate-early
      genes as regenerating liver, Stat3 is not induced in these cells. Because Stat
      factors are known to be inactivated by protein tyrosine phosphatases (PTPase), we
      showed that a PTPase is able to eliminate the DNA binding of hepatic
      Stat3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737652
TI  - Mitochondrial oxidative phosphorylation and intracellular glutathione
      compartmentation during rat liver regeneration.
AB  - The rate of mitochondrial oxidative phosphorylation and the cytosolic and
      mitochondrial total and oxidized glutathione concentrations were studied in
      regenerating rat livers after partial (70%) hepatectomy. The rate of
      mitochondrial oxidative phosphorylation progressively decreased during the early
      prereplicative phase of liver regeneration. This was accompanied by a progressive
      decrease in mitochondrial, but not cytosolic, glutathione concentration. Twenty
      four hours after partial hepatectomy, both the rate of adenosine triphosphate
      (ATP) synthesis and the amount of mitochondrial glutathione were depressed by 50%
      with respect to controls (sham-operated animals). During the second replicative
      phase, both the oxidative phosphorylation rate and mitochondrial glutathione
      concentration were recovered; however, the kinetics of the recovery were
      different, being the total amount of mitochondrial glutathione completely
      restored 48 hours after partial hepatectomy, whereas 72 hours were needed for the
      recovery of oxidative phosphorylation. The decrease in the rate of oxidative
      phosphorylation, during the early phase of liver regeneration, appeared to be
      secondary to the decreased content of the catalytic subunit beta-F1 of the ATP
      synthase complex, which in turn was shown to be linearly related to the decrease
      of intramitochondrial glutathione. These observations suggest that the two
      phenomena may be due to the previously reported increased free radical production
      during the early phase of liver regeneration. The depression of mitochondrial
      glutathione after partial hepatectomy may play a contributory role in structural
      and functional alterations of mitochondria occurring in the first
      retrodifferential phase of liver regeneration.

PMID- 7737653
TI  - Hormone-induced bile flow and hepatobiliary calcium fluxes are attenuated in the
      perfused liver of rats made cholestatic with ethynylestradiol in vivo and with
      phalloidin in vitro.
AB  - The actions of vasopressin and glucagon, administered alone or together, were
      assessed on bile flow in perfused livers from rats made cholestatic by the
      injection of ethynylestradiol and from those allowed to recover from such
      treatment. Concomitant measurements were made of biliary calcium output as well
      as changes in the perfusate Ca2+ concentration, glucose output, and oxygen
      uptake. Experiments were also conducted where cholestasis was induced in vitro in
      the perfused liver by the infusion of phalloidin. In each case cholestasis was
      demonstrated to have occurred by a reduction in bile flow by approximately 50%.
      The data show that the transient increase in bile flow and bile calcium seen in
      control rat liver soon after the administration of vasopressin, particularly when
      coadministered with glucagon, is largely absent in cholestasis induced by
      ethynylestradiol and attenuated in cholestasis induced by phalloidin. At the same
      time the pattern of perfusate Ca2+ fluxes in ethynylestradiol-induced cholestasis
      shifts to one reflecting net efflux of the ion from the liver. The responses to
      glucagon administration alone contrast with those of vasopressin in that in the
      perfused liver of ethynylestradiol-treated rats, glucagon induces a pronounced
      and sustained increase in bile flow. In cholestasis induced by both
      ethynylestradiol and phalloidin, glucagon fails to induce an initial transient
      decrease in bile flow. The effects of glucagon, including enhancement of
      vasopressin-stimulated bile flow in control and in ethynylestradiol-treated rats,
      can be mimicked by dibutyryl cyclic adenosine monophosphate (cAMP). Changes in
      glucose output and oxygen uptake induced by both hormones are only slightly
      attenuated. The data show that the modulation of bile flow that occurs rapidly
      after the administration of vasopressin and glucagon to control perfused rat
      liver is altered in conditions of cholestasis induced by either ethynylestradiol
      or phalloidin.

PMID- 7737654
TI  - In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among
      apoptosis, necrosis, and autolytic cell death: a cautionary note.
AB  - Detection of DNA fragments in situ using the terminal deoxyribonucleotidyl
      transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay is
      increasingly applied to investigate active cell death (apoptosis). We studied the
      specificity of the assay in well-defined models of apoptosis and necrosis as well
      as in postmortem autolysis in rat liver. During involution of liver hyperplasia,
      which follows stopping treatment with the hepatomitogens cyproterone acetate
      (CPA) or nafenopin (NAF), numerous apoptotic hepatocytes could be observed with
      TUNEL-positive chromatin residues. A similar TUNEL-positive reaction appeared in
      necrotic hepatocytes after a cytotoxic dose of carbon tetrachloride (CCl4) or N
      nitrosomorpholine (NNM). Also, in insufficiently fixed, autolytic livers TUNEL
      positive nuclei were observed. Thus, DNA fragmentation is common to different
      kinds of cell death; its detection in situ should not be considered a specific
      marker of apoptosis.

PMID- 7737655
TI  - Ursodeoxycholic acid therapy in primary biliary cirrhosis.

PMID- 7737656
TI  - The enigma of anti-neutrophil antibodies in ulcerative colitis primary sclerosing
      cholangitis: important genetic marker or epiphenomenon?

PMID- 7737657
TI  - Assessment of cell proliferation in pathology--what next?
AB  - This brief overview outlines recent progress in our understanding of the
      regulation of cell population size, focusing on some important developments in
      cell cycle control and the recognition of the importance of growth arrest and
      cell death. Histopathologists, and others with an interest in tissue
      architecture, have much to offer to those who study the biochemical and molecular
      processes of proliferation, growth arrest and cell death, and these processes are
      unlikely to be understood simply by analysis of in vitro systems and cell lines.
      Such biochemical and histological information may well feed back into clinical
      medicine in terms of new approaches and techniques, new reagents and new
      paradigms. With regard to the application of measures of proliferation, growth
      arrest and cell death as prognostic factors or other diagnostic tools, we are
      sceptical. Methods for assessing cell proliferation seem unlikely to be
      implemented widely in practice since there is little direct evidence that they
      are really an improvement on conventional histological assessment, optimally
      employed. But, there again, we may be proved wrong! In particular, it may be
      that, if carefully employed, assays that integrate information about death,
      growth arrest and proliferation may be clinically valuable.

PMID- 7737658
TI  - Complete hydatidiform mole in twin pregnancy: differentiation from partial mole
      with interphase cytogenetic and DNA cytometric analyses on paraffin embedded
      tissues.
AB  - Six cases of hydatidiform mole associated with normal chorionic villi and a
      normal embryo/fetus (in five cases) were investigated with interphase cytogenetic
      and DNA cytometric analyses for diagnostic purposes. DNA probes specific for the
      pericentromeric regions of chromosomes 1 and X and for the long arm of chromosome
      Y were used. In four cases a dizygotic twin pregnancy could be proven. In these
      cases, the histologically normal chorionic villi showed an XY DNA-diploid
      pattern, consistent with a normal male conceptus, and the molar chorionic villi a
      XX pattern. In the other two cases an identical sex chromosomal pattern was found
      in the normal and in the molar villi (XX/XX and XY/XY respectively). In all six
      cases the molar placental tissues showed prominent trophoblastic hyperplasia with
      DNA-polyploidy, consistent with a complete hydatidiform mole. In two cases
      persistent gestational trophoblastic disease developed. It is emphasized that
      twin pregnancies composed of a normal conceptus and a complete mole have a
      relatively high risk for the development of persistent trophoblastic disease and
      therefore, should be carefully differentiated from triploid partial moles with a
      relatively low risk of persistent gestational trophoblastic disease. These case
      reports indicate that additional interphase cytogenetic and DNA cytometric
      analyses are useful in this differential diagnosis.

PMID- 7737659
TI  - DNA flow cytometric analysis in renal neoplasms associated with acquired renal
      cystic disease.
AB  - In order to better understand the potential malignancy of renal neoplasms arising
      in patients with acquired renal cystic disease and to try and establish
      differences from other renal tumours we analysed DNA ploidy as well as the level
      of S-phase fraction in 11 neoplasms associated with acquired cystic disease by
      means of flow cytometry. The results were correlated with known prognostic
      factors such as nuclear grade, size and stage, as well as the clinical behaviour
      of the tumours. We found a close relationship between DNA aneuploidy and high S
      phase fraction and a poor clinical outcome. We also found some differences in the
      DNA ploidy profile of these tumours when compared with those reported in other
      renal neoplasms.

PMID- 7737660
TI  - The choroid plexus carcinomas of childhood: histopathology, immunocytochemistry
      and clinicopathological correlations.
AB  - Anaplastic choroid plexus carcinoma is a tumour with a predilection for the
      posterior fossa of infants and can be difficult to distinguish histologically
      from medulloblastoma without the aid of immunocytochemistry using a panel of
      antibodies. Of a series of 17 choroid plexus carcinomas (five of which were
      classed as moderately differentiated and 12 as anaplastic) 17 expressed antigens
      to transthyretin, transferrin and cathepsin and 16 expressed carbonic anhydrase
      II. Eleven expressed at least one epithelial marker (cytokeratin or epithelial
      membrane antigen). In contrast, none of six medulloblastomas expressed epithelial
      markers, transrythetin, carbonic anhydrase II or transferrin, though three were
      positive with antibodies to cathepsin.

PMID- 7737661
TI  - Mixed tumours of the skin: a histopathological, enzyme-histochemical and
      immunohistochemical study.
AB  - Twenty-eight cases of mixed tumour of the skin were studied and subclassified
      into three types: eccrine (1 case), indeterminate (7), and apocrine type (20).
      The indeterminate type was defined as mixed tumours having tubuloalveolar
      patterns with two layers of epithelium, ut without apocrine secretion or
      pilosebaceous differentiation. Enzyme-histochemical studies were performed on
      four cases (one indeterminate, three apocrine): in the indeterminate type the
      tubular epithelial cells showed eccrine differentiation while in the apocrine
      type tubules were found showing the direction of differentiation to be toward the
      apocrine gland, but tubules with eccrine differentiation were intermingled in all
      three. Immunohistochemically, no differences were observed between the
      indeterminate and the apocrine type: hints of eccrine features were observed in
      both groups. Thus, the indeterminate type could be an eccrine tumour and the
      apocrine type showed direction of differentiation toward both eccrine and
      apocrine glands. It is concluded that mixed tumours of the skin are fundamentally
      eccrine neoplasmas, and that the apocrine features may represent apocrine
      metaplasia.

PMID- 7737662
TI  - Pseudomalignant perineurial invasion in cellular ('infantile') capillary
      haemangiomas.
AB  - One hundred and sixty-eight cellular ('infantile') capillary haemangiomas were
      assessed for the presence of perineurial invasion, a feature that can lead to the
      erroneous diagnosis of malignancy. Fourteen tumours (8%) showed unequivocal,
      usually prominent, involvement of small and medium sized nerves. Eleven of these
      lesions presented in infants at birth or shortly thereafter, two in young adults
      and one in a middle-aged adult. Ten patients were females. Ten of the lesions
      arose in the head and neck region, one in the arm, one in the chest wall, and in
      two the site was not stated. Follow-up revealed a local recurrence in only one of
      six cases. Histologically, all cases were typical pure capillary haemangiomas
      composed of lobules of small blood vessels, lined by bland endothelial cells,
      involving the dermis, subcutis or both. One case was an intramuscular capillary
      haemangioma. Long-standing cases, especially those in adults, were less cellular,
      with focal fibrosis and a myxoid stroma. Neural invasion was detected either in
      the centre or at the periphery of tumour lobules and was characterized by the
      presence of variable numbers of capillaries within the perineurium and in close
      contact with Schwann cells. This feature was highlighted by immunostaining for S
      100 protein and EMA. In one case, extensive invasion of medium-sized deep dermal
      veins was also present, focally simulating an intravascular pyogenic granuloma.
      This study demonstrates that perineurial invasion in infantile capillary
      haemangiomas is a relatively common finding and should not be regarded as
      evidence of malignancy.

PMID- 7737663
TI  - Angiosarcoma of the larynx.
AB  - The morphological and immunohistochemical features of a laryngeal angiosarcoma
      are described. Initially, the tumour was interpreted as a poorly differentiated
      squamous cell carcinoma. The laryngectomy specimen contained an extensive and
      haemorrhagic tumour consisting of irregular and dissecting vascular spaces
      delineated by pleomorphic endothelial cells. In addition to these obvious
      angiosarcomatous areas, islands of more compact growing tumour cells were
      present, reminiscent of a poorly differentiated squamous cell carcinoma. On
      immunohistochemistry, the tumour cells expressed factor VIII, Ulex europaeus I
      lectin, CD31 and vimentin. There was no expression of cytokeratin or epithelial
      membrane antigen. Angiosarcoma of the larynx is very rare and should be
      differentiated from a pseudo-angiosarcomatous carcinoma.

PMID- 7737664
TI  - Intracytoplasmic lumina and mucinous inclusions in ovarian carcinomas.
AB  - Intracytoplasmic mucinous inclusions and lumina have been previously described in
      non-glandular neoplasms such as urothelial carcinoma. We describe their presence
      in 93% of non-mucinous ovarian carcinomas. They were found in abundance in all 25
      cases (100%) of clear cell carcinoma, in 48 of 50 cases (96%) of serous carcinoma
      and 20 of 25 cases (80%) of endometrioid carcinoma. The degree of the
      differentiation of the tumour did not influence the number of inclusions or
      lumina observed. These results suggest that the presence of intracytoplasmic
      lumina and mucinous inclusions is more widespread than hitherto appreciated.
      Their presence in an otherwise poorly differentiated metastatic carcinoma might,
      at the very last, prompt one to consider the ovary as a possible primary site. In
      addition, an abundance of intracytoplasmic mucinous inclusion and lumina with
      microcyst formation, in an otherwise poorly differentiated malignant primary
      ovarian epithelial tumour, might suggest the possibility of a clear cell
      carcinoma.

PMID- 7737665
TI  - Metastasising eccrine syringomatous carcinoma.

PMID- 7737666
TI  - Intranodal leiomyoma or myofibroblastoma: an identical lesion?

PMID- 7737667
TI  - Primary anaplastic large cell lymphoma of the rectum.

PMID- 7737668
TI  - Neuroblastoma-like epithelioid schwannoma.

PMID- 7737669
TI  - Intraneural leiomyoma.

PMID- 7737670
TI  - An immunodominant epitope in a functional domain near the N-terminus of human
      granulocyte-macrophage colony-stimulating factor identified by cross-reaction of
      synthetic peptides with neutralizing anti-protein and anti-peptide antibodies.
AB  - We produced polyclonal and monoclonal antibodies (MAbs) against recombinant human
      (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and performed
      studies of epitope mapping by ELISA, using five synthetic peptides corresponding
      to sequences along this molecule. Additionally, anti-peptide MAbs were generated.
      The antibody ability to inhibit rhGM-CSF activity was determined using as
      bioassay the MO7e cell line, which is dependent on hGM-CSF for growth in vitro.
      An immunodominant epitope able to induce the highest neutralization antibody
      titers was identified near the N terminus of hGM-CSF. A synthetic peptide 14-24,
      homologous to a sequence including part of the first alpha-helix of the molecule,
      was recognized by neutralizing anti-protein antibodies. Similarly, MAbs anti- 14
      24 cross-reacted with rhGM-CSF and specifically blocked its function. Replacement
      of Val16 or Asn17 with alanine greatly reduced the antibody-binding capacity to
      peptide 14-24, whereas substitution of Gln20 or Glu21 was less critical.
      Monoclonal antibodies generated against residues 30-41 (corresponding to an
      intrahelical loop) and 79-91 (homologous to a sequence including part of the
      third alpha-helix) or its analog [Ala88](79-91)beta Ala-Cys, were conformation
      dependent and nonneutralizing: they failed to react or bound poorly to rhGM-CSF
      in ELISA, but readily recognized the homologous sequence in the denatured
      protein, by Western blotting.

PMID- 7737671
TI  - Chimerization of LL2, a rapidly internalizing antibody specific for B cell
      lymphoma.
AB  - LL2 is a murine monoclonal antibody (MAb) that has been shown to be effective for
      the diagnosis and treatment of patients with non-Hodgkin's B cell lymphoma.
      Studies have also shown that radiolabeled murine LL2 (mLL2) or mLL2 and fragments
      thereof coupled to Pseudomonas exotoxin (PE) can effectively target human B cell
      lymphoma in mice. We have obtained the DNA sequences encoding the VK and VH
      domains of mLL2, an IgG2a MAb, which were combined with their respective human
      kappa and IgG1 constant region domains and expressed in SP2/0 cells. Like its
      murine counterpart, the chimeric LL2 (cLL2) antibody is glycosylated in the light
      chain variable region. Chimerization did not interfere with the immunoreactivity
      of the antibody, as determined by a competitive binding assay, where either
      antibody shows equivalent inhibition of the binding of its counterpart to the
      Raji cell membrane surface antigen, CD22. Both antibodies bind and are rapidly
      internalized by Raji cells, whereas an irrelevant humanized antibody did not bind
      and was not internalized under similar conditions. The internalization rates of
      the bound murine or chimeric antibodies were nearly identical, with Ke values of
      0.106 and 0.118 min-1 for mLL2 and cLL2, respectively. The observed close
      equivalence between the murine and chimeric antibodies suggests potential
      advantages of the latter as a less immunogenic agent. Studies are currently
      underway to evaluate the chimeric antibody as a potential therapeutic
      immunoconjugate.

PMID- 7737672
TI  - Monoclonal antibodies can reveal immunoreactivity differences between pituitary
      and recombinant bovine growth hormone.
AB  - Monoclonal antibodies (MAbs) to pituitary bovine growth hormone (bGH) were used
      to assay the immunoreactivity of a recombinant form of bGH. The recombinant
      hormone used differed from the pituitary principally in the presence of a short
      amino acid sequence starting with methionine added to the N-terminal end of the
      molecule. Monoclonal antibody 1D2 recognized the recombinant hormone with greater
      affinity than the pituitary hormone, whereas MAb 5G1 bound the recombinant
      molecule with a lower strength than the pituitary. The other MAbs showed
      different behavior depending on the type of immunoassay used. Results indicate
      that the recombinant bGH molecule has been altered in its immunological
      structure, and suggest a possible interaction of the added N-terminal fragment
      with the three-dimensional structure of the hormone.

PMID- 7737673
TI  - A monoclonal antibody to a cytoskeletal protein selectively recognizing malignant
      neuroectodermal tumors.
AB  - Fusion of myeloma (P3X63-Ag 8.653) cells with spleen cells from BALB/c mice
      immunized with human neuroblastoma (SK-N-SH) cells yielded a hybridoma clone,
      referred to as 3XB7, with a unique pattern of reactivity to malignant
      neuroectodermal tumors except gliomas of low-grade malignancy. Indirect
      immunofluorescence staining under different conditions and Western blot analysis
      indicate that the 3XB7 MAb recognizes an intracellular cytoskeletal protein of
      M(r) 52K. Immunohistochemical studies with cryostat and paraffin-embedded
      sections from tumor biopsies revealed that the 3XB7 MAb specifically recognizes
      malignant neuroectodermal tumors and reacts negatively with other epithelial and
      mesenchymal tumors, e.g., carcinomas, lymphomas, and sarcomas as well as with
      normal adult and fetal brain tissues. Negative reaction was also observed with
      other small round cell tumors of childhood. Thus the 3XB7 antigen can be used for
      diagnosis of all stages of neuroblastomas, and its specific expression in gliomas
      with high-grade malignancy (grades III and IV) confer on it additional prognostic
      value.

PMID- 7737674
TI  - Preparation and characterization of polyclonal and monoclonal antibodies specific
      for covalently linked DNA/RNA cross sections.
AB  - Covalently linked cross sections refer to structures that mimic hydrogen-bonded
      purine-pyrimidine, purine-purine, and pyrimidine-pyrimidine duplexes. Cross
      sections dA [symbol:see text] U and A [symbol: see text] dT, which have been
      synthesized chemically, have molecular dimensions similar to purine-pyrimidine
      base pairs in a double helix. We propose that antibodies to such covalent cross
      sections might facilitate the study of the pathogenesis of specific diseases or
      of biochemical processes in which base pair involvement is suspected and/or
      demonstrated. We have made polyclonal antibodies against "A:U" and "A:T" cross
      sections by immunizing rabbits with dA [symbol: see text] U and A [symbol: see
      text] dT, each conjugated to keyhole limpet hemocyanin (KLH). The antibodies were
      found to be highly specific for the cross sections and to cross react minimally
      to single nucleosides. Hybridomas secreting monoclonal antibodies to "A:T" were
      then generated from spleen cells of mice immunized with A [symbol: see text] dT
      conjugated to KLH. The MAbs produced were also found to be highly specific for
      "A:T" among various nucleosides. In fact, the binding of most of the monoclonal
      antibodies to "A:T" was only partially inhibited by high concentrations of
      adenosine or thymidine. All monoclonal antibodies to "A:T" cross react, but with
      lower affinity, to "A:U." Selected MAbs showed greater inhibition of binding to
      "A:T"-BSA by A + T than by A or T alone.

PMID- 7737675
TI  - Purification of bispecific F(ab')2 from murine trinoma OC/TR with specificity for
      CD3 and ovarian cancer.
AB  - A study was made of the stability of the murine bispecific trinoma OC/TR with
      respect to secretion of both types of parental heavy and light chains. OC/TR is a
      cell line producing bispecific antibody that reacts with the CD3 antigen on T
      cells and the folate-binding receptor--frequently found to be overexpressed on
      ovarian carcinoma cells. Of the 10 different IgG combinations theoretically
      possible with 2 heavy and 2 light chains, 6 combinations were secreted. Subclones
      varied considerably in relative production of the two parental heavy and light
      chains. A detailed analysis was made of the binding characteristics and
      retargeting activity of each of the IgGs produced. From a clone producing a
      relatively high quantity of bispecific IgG, a large-scale production was
      initiated. The purification of clinical grade bispecific F(ab')2 from harvest
      fluids is described. The yield from this purification process was found to be
      comparable to the yield of bispecific F(ab')2 after chemical cross-linking of two
      different Fab'.

PMID- 7737676
TI  - Isolation and characterization of two monoclonal antibodies raised against tms1
      protein of fission yeast.
AB  - Monoclonal antibodies were produced against recombinant tms1 protein of fission
      yeast. The antibodies of IgG3 subclass were isolated from serum-free cell culture
      medium and purified by affinity chromatography on protein A-Sepharose. The
      antibodies can be used to detect specifically the tms1 protein on immunoblots of
      total yeast lysates. In addition, native tms1 protein is specifically
      precipitated by these antibodies from yeast lysates.

PMID- 7737677
TI  - Simultaneous expression of kappa and lambda light chains in a murine IgG3 anti
      Cryptococcus neoformans hybridoma cell line.
AB  - Allelic exclusion normally results in the expression of only one light and one
      heavy chain gene. However, some hybridomas have been reported to express two
      different heavy chain genes. Here we report that the IgG3 hybridoma 4H3.C8B
      expresses both kappa and lambda light chains. 4H3.C8B was originally recovered by
      screening for antibody binding to Cryptococcus neoformans polysaccharide antigen
      and characterized as gamma 3 lambda. The gamma 3 lambda but not the gamma 3 kappa
      binds to polysaccharide antigen. Some of the antibody molecules were heterodimers
      composed of both lambda and kappa. IgG1 and IgG2b isotype switch variants were
      identified and isolated by the technique of sib selection, using the ELISA spot
      assay. Like the parent IgG3 line, the switch variants continued to express both
      kappa and lambda light chains but only the lambda-containing antibodies bound to
      the antigen. Our experience suggests that hybridomas recovered by assays that are
      antigen dependent should also be tested for the expression of other isotypes and
      light chains in a non-antigen-binding immunoassay.

PMID- 7737678
TI  - A monoclonal antibody against the plant growth regulator, abscisic acid.
AB  - Monoclonal antibodies were prepared against the plant growth regulator abscisic
      acid (ABA) conjugated to keyhole limpet hemocyanin through C-4. One of these
      antibodies was characterized for use in a competition fluorescence enzyme-linked
      immunosorbent assay (F-ELISA). The antibody detected femtomole quantities of ABA
      when used in the F-ELISA and showed minimal cross-reactivity with ABA metabolites
      and structural analogs. Dilution analysis suggested that the F-ELISA could be
      used to determine the ABA content of methanolic extracts of crude samples of
      wheat seeds without further purification. The F-ELISA was used to determine the
      effect of seed priming on ABA levels in wheat seeds. The antibody also was used
      in a modified noncompetitive indirect ELISA to measure ABA content of wheat
      caryopses. The noncompetitive ELISA was more sensitive than the F-ELISA, although
      the F-ELISA had a broader measuring range. When our anti-ABA antibody and a
      commercially available anti-ABA antibody were compared by indirect ELISA, there
      were no significant differences between the ABA estimates.

PMID- 7737680
TI  - The 4th Elsinore Meeting of Infection Immunity. Macrophages in Infection
      Immunity. Elsinore, Denmark, 20-24 May 1994. Proceedings.

PMID- 7737679
TI  - Production and characterization of specific bovine plasminogen monoclonal
      antibodies.
AB  - A collection of monoclonal antibodies was raised against bovine plasminogen by
      immunizing mice with purified plasminogen. More than 300 positive clones were
      obtained in 1 fusion experiment (1300 hybrids tested). Four types of antibodies
      were characterized through their relative binding to plasmin and plasminogen in
      ELISA. About one-third was strictly specific to plasminogen; the selectivity of
      this group was confirmed by immunoblots and BIA-core analysis. Cross-reactivity
      against horse, human, pig, sheep, rabbit, and bovine plasminogens was tested; 41%
      were strictly bovine specific.

PMID- 7737681
TI  - Cytokines and natural regulators of cytokines.

PMID- 7737682
TI  - The immunological potential of apoptotic debris produced by tumor cells and
      during HIV infection.
AB  - Apoptosis is a major cause of cell death in health and disease. In contrast to
      necrosis, apoptosis does not induce an inflammatory response and the cellular
      debris produced by apoptosis has been assumed to be biologically inert. This
      review challenges this assumption by suggesting that apoptotic debris (especially
      in the context of growing tumors or during HIV infection) may have immunological
      activities, mainly immunosuppressive but perhaps also immunostimulatory. In many
      cases, the surface of apoptotic cells differs from normal cells in that
      phosphatidylserine (PS) is aberrantly exposed on the external face of the cell
      membrane. Liposomes composed of PS may down-modulate macrophage anti-leishmanial
      activities, suppress macrophage TNF production, suppress lymphocyte
      proliferation, and increase macrophage proliferation. "Membrane shedding" has
      been described in certain malignancies where apoptosis may be occurring, and the
      shed tumor membrane vesicles have been shown to reduce MHC class II expression on
      macrophages and decrease lymphocyte responsiveness, perhaps because of their
      ganglioside content. Finally, the apoptotic debris from HIV-infected cells may
      bear on its surface viral proteins which contain immunosuppressive peptide
      sequences. This debris may also use viral envelope proteins to fuse into
      macrophages and thereby avoid phagocytosis and lysosomal destruction. These
      considerations suggest that the flux of apoptosing cells and debris through the
      immune system that occurs during tumor growth and HIV infection should not be
      assumed to be immunologically neutral. In particular, HIV-related apoptosis may
      have immunosuppressive effects in addition to the numerical depletion of
      lymphocytes.

PMID- 7737683
TI  - Familial disseminated atypical mycobacterial disease.
AB  - Mycobacterial disease remains a major public health problem and there appears to
      be a genetic component underlying susceptibility. This paper describes a group of
      related children who appear to have a genetic predisposition to disseminated
      atypical mycobacterial infection. Identification of the defect in this group
      could lead to better understanding of the genetics of susceptibility to
      mycobacterial infection.

PMID- 7737684
TI  - Expression of soluble T-cell receptor fragments derived from a T-cell clone
      associated with murine collagen-induced arthritis.

PMID- 7737685
TI  - Cytokine dysregulation and the initiation of systemic autoimmunity.
AB  - Autoimmunity (AI) exemplifies the potent and destructive activity expressed by
      the immune system when normal constraints against self-reactivity are lost or
      compromised. We have previously described a dramatic and intrinsic defect in
      cytokine expression in macrophages (M phi) from young AI-prone mice [1-3]. There
      are two points in particular that we believe speak to the importance of this
      observation: (i) Cytokine dysregulation is distinguished from many of the
      aberrancies reported in AI-prone mouse strains in that, as an inherent trait, it
      cannot arise as a consequence of the disease process. (ii) This defect is a
      remarkably consistent characteristic of M phi from strains that develop
      manifestations of systemic AI, including MRL/+, NZB, NZB/W F1, BXSB, and NOD, and
      distinguishes these strains from mice whose disease is predicated on defects in
      apoptosis (e.g., the lpr and gld mutations). The multigenic basis for disease and
      renal pathology in the former strains more closely mirror human lupus than do the
      disease manifestations of lpr and gld mice. In light of clear evidence that
      cytokines are key mediators of lymphocyte growth and function, a defect in the
      cytokine network has the potential to disrupt the normal regulation of self
      reactivity, leading to the initiation of systemic AI.

PMID- 7737687
TI  - Participation of intracellular oxidative pathways in antigen processing by
      dendritic cells, B cells and macrophages.
AB  - The antigen presentation abilities of antigen presenting cells (APC) from
      different lineages [mainly macrophages (M phi), B cells and dendritic cells (DC)]
      were compared. In this review we focus on the participation of intracellular
      oxidative mechanisms in intracellular degradation of protein antigens: an aspect
      that is often neglected when the issue of antigen processing is considered.
      Special emphasis is given to recent findings from our laboratory indicating that
      in addition to a lysosomal proteolytic step being present in all APC, a previous
      or simultaneous oxidative step is operative in some APC (M phi) but absent or
      less important in others (B cells, DC).

PMID- 7737686
TI  - Identification of MIF as a new pituitary hormone and macrophage cytokine and its
      role in endotoxic shock.
AB  - The protein mediator described originally as macrophage migration inhibitory
      factor has been "rediscovered" to be both a novel pituitary hormone and a pro
      inflammatory, macrophage-derived cytokine. MIF plays a pivotal role in the host
      response to endotoxic shock and appears to serve as a pituitary "stress" hormone
      that regulates systemic inflammatory responses.

PMID- 7737688
TI  - Dendritic cells from HIV-1 infected individuals show reduced capacity to
      stimulate autologous T-cell proliferation.
AB  - Dendritic cells (DC) exposed for a short period of time (1 day) in vitro to HIV
      infection caused stimulation of autologous T-cells, but those exposed for a
      longer period (3 days) before addition to T-cells stimulate little or no
      proliferation [1]. Since a proportion of DC from patients who are HIV-1
      seropositive is infected with HIV-1 [2] we used the same culture system to test
      the level of ongoing stimulation of autologous T-cells by DC. The DC from
      patients with HIV-1 infection showed no enhanced stimulation of autologous T
      cells; they produced significantly lower levels of proliferation than those
      induced by DC from normal controls or from high risk seronegative individuals.
      However, DC stimulated production of antibodies to gp120 and p24 in cultures
      containing autologous B plus T-cell in the absence of any added exogenous
      antigens as previously described [3]. DC in asymptomatic individuals thus appear
      to be fuelling antibody production but not T-cell proliferation. The results
      suggest that a failure by DC to stimulate T-cell proliferation either to HIV-1 or
      to other environmental antigens may be involved in the failure of cell-mediated
      responses in HIV infection.

PMID- 7737689
TI  - The bio-logical role of invariant chain (Ii) in MHC class II antigen
      presentation.
AB  - Foreign antigens are internalized by antigen presenting cells by endocytosis and
      processed to peptides. To enable presentation of antigenic peptides by MHC class
      II molecules, these molecules have to be sorted to endosomal compartments where
      they can meet and bind the peptides. Invariant chain is complexed with MHC class
      II molecules and contains sorting signals responsible for MHC class II
      accumulation in endosomes. Invariant chain also has several other features
      contributing to the immune system's specific combat against invaders.

PMID- 7737690
TI  - Presentation of the Plasmodium falciparum antigen Pf155/RESA to human T cells.
      Variations in responsiveness induced by antigen presenting cells from different
      but MHC class II identical donors.
AB  - The antibody response in humans naturally primed to a malaria vaccine candidate
      antigen (Pf155/RESA) is genetically regulated. Here, the impact of antigen
      presenting cells (APC) on the control of in vitro T-cell responses induced by
      Pf155/RESA or synthetic peptides corresponding to its major Pf155/RESA epitopes
      was studied. T cells and APC were from the peripheral blood of monozygotic or
      dizygotic twins and their age matched siblings, all living in the central
      highlands of Madagascar. When induced to proliferate (thymidine incorporation) in
      vitro by antigenic peptides, the T-cell responses varied less within the twin
      pairs than between them and their siblings or the entire group, implying that
      they were genetically regulated. Occasional MHC class II associations of some of
      the responses were weak and did not reflect underlying MHC class II restrictions.
      When T cells and APC from different but MHC class II identical donors were
      incubated in various combinations, antigen charged APC from homologous donors
      induced in vitro T-cell proliferation which differed from that induced by the T
      cell donors' own APC. Pretreatment of the APC with either paraformaldehyde or
      anti-class II antibodies inhibited or abolished this antigen dependent T-cell
      proliferation. The results suggest that the observed differences in T-cell
      responses induced by APC from different donors reflect differences at the level
      of these cells. Whether they reflect differences in the proteases involved in
      antigen processing, in the costimulatory signals provided by the APC to the T
      cells or in the secretion of other regulatory factors remains to be elucidated.

PMID- 7737691
TI  - Pathways of macrophage activation and innate immunity.

PMID- 7737692
TI  - Murine M phi scavenger receptor: adhesion function and expression.
AB  - In the absence of divalent cations M phi lose their spread morphology but remain
      adherent to tissue culture treated plastic. We have exploited this property of M
      phi adhesion in vitro, to isolate a rat monoclonal 2F8, which totally inhibits
      the divalent cation-independent adhesion of M phi to tissue culture treated
      plastic and is partly responsible for the trypsin-resistant adhesion of M phi to
      the same substratum. Immunoprecipitation from macrophages and stably transfected
      Chinese Hamster Ovary Cells revealed that the antigen recognised by monoclonal
      antibody 2F8 is identical to the murine macrophage scavenger receptor. Macrophage
      scavenger receptors are trimeric integral membrane glycoproteins which have been
      implicated in various macrophage functions including uptake of oxidised
      lipoprotein and the formation of foam cells in atherosclerotic lesions. We have
      used monoclonal antibody 2F8 to explore the expression of murine macrophage
      scavenger receptor in lymphoid and non-lymphoid organs of the normal adult mouse
      and to examine the contribution of macrophage scavenger receptor to macrophage
      adhesion within tissues.

PMID- 7737693
TI  - Cytokine and growth factor regulation of macrophage scavenger receptor expression
      and function.
AB  - Regulation of macrophage scavenger receptor (MSR) activity may be an important
      determinant of the extent of atherogenesis and the efficacy of host defense. The
      effect of M-CSF on this pathway was studied using a recently developed monoclonal
      antibody to murine MSR. M-CSF markedly and selectively increased MSR synthesis in
      murine macrophages (M phi); post-translationally the receptor appeared more
      stable and shifted to a predominantly surface distribution. Functionally M-CSF
      enhanced modified lipoprotein uptake and increased divalent cation-independent
      adhesion in vitro. These results suggest a plausible mechanism whereby M-CSF
      production in the atheromatous plaque microenvironment could promote the
      recruitment and retention of mononuclear phagocytes and subsequent foam cell
      formation. In addition, the Th1 cytokine (gamma-interferon) and Th2 cytokine
      (interleukin-4) had differential effects on MSR glycosylation in vitro suggesting
      a further possible regulatory role by these lymphokines on macrophage MSR
      function.

PMID- 7737694
TI  - The pathology of malaria: a possible target for immunisation?

PMID- 7737695
TI  - Regulation of nitric oxide synthesis in infectious and autoimmune diseases.
AB  - Nitric oxide (NO) is an essential mediator for a variety of biological functions,
      including defence against a range of pathogens. However, excessive production of
      NO as a result of immunological stimulation, will lead to important
      immunopathologies. Therefore the production of NO is necessarily under tight
      regulation. The regulatory mechanisms so far known to control NO synthesis
      include cytokines (induction of NO synthase by IFN-gamma, TNF alpha, MIF and LPS,
      and down regulation by IL-4, IL-10 and TGF beta), feedback inhibition by NO
      itself, inhibition by pretreatment with LPS and glycoinositol-phospholipids and
      up regulation by lipophosphoglycan from the protozoa parasite, Leishmania major.

PMID- 7737696
TI  - Genetic regulation of leishmanial and mycobacterial infections: the Lsh/Ity/Bcg
      gene story continues.
AB  - A common basis to genetic regulation of leishmanial and mycobacterial infections
      is provided by the action of the murine Lsh/Ity/Bcg gene in controlling the
      priming/activation of macrophages for antimicrobial activity. This relies on the
      TNF-alpha-dependent sustained expression of the inducible nitric oxide synthase
      (iNOS) gene responsible for the generation of large amounts of toxic nitric oxide
      (NO). The Lsh/Ity/Bcg gene has many pleiotropic effects, including differential
      expression of the early response gene KC following stimulation of macrophages
      with bacterial lipopolysaccharide (LPS) and mycobacterial lipoarabinomannan
      (LAM). The major signal transduction pathway involved in KC induction requires
      the generation of low levels of NO via constitutive nitric oxide synthase (cNOS)
      activity, leading to activation of guanylate cyclase and the cGMP-dependent
      kinase pathway. NO therefore appears to provide a common link between the early
      influence of Lsh in regulating the expression of genes which mediate many
      pleiotropic effects, and the later production of NO as the final effector
      mechanism for kill. The recently cloned candidate for Lsh/Ity/Bcg, designated
      Nramp for Natural resistance associated macrophage protein, encodes a polytopic
      integral membrane protein that has structural features common to prokaryotic and
      eukaryotic transporters and includes a conserved binding-protein-dependent
      transport motif which may be involved in interaction with peripheral ATP-binding
      subunits. The N-terminal sequence also carries a proline/serine rich putative SH3
      binding domain, consistent with a role for tyrosine kinases in regulating Nramp
      function. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737697
TI  - HIV infection and tuberculosis.

PMID- 7737698
TI  - Pleural involvement in HIV infection: clinico-radiological profile and prognostic
      significance.
AB  - The clinico-radiological profile of seven patients with pleural involvement and
      HIV infection is presented. Five out of seven subjects had a right-sided
      effusion. The aetiology in three cases; two tubercular and one invasive
      candidiasis was established by pleural biopsy. The mortality was high (5/7)
      indicating a poor prognosis in patients of HIV with pleural involvement.

PMID- 7737699
TI  - A comparison of inhaled salbutamol with a combination of salbutamol and
      beclomethasone dipropionate in moderately severe asthma.
AB  - Fifteen adults with moderately severe asthma underwent two sequential treatments,
      first with inhaled salbutamol, 200 micrograms q.i.d. for 2 weeks followed by a
      combination of salbutamol 200 micrograms and beclomethasone dipropionate (BDP)
      100 micrograms q.i.d. for the next 2 weeks. The response was evaluated by
      symptoms and additional drugs scores during the two treatments and spirometry
      before and after each treatment. The second phase of treatment resulted in a
      greater symptomatic improvement and a reduced need for additional drugs. A
      clinically significant improvement was observed in lung function after the
      combination treatment. However, as the comparison was limited to only 2 weeks,
      this duration of treatment was not adequate to correct the spirometric
      abnormalities. It was concluded that a combination of salbutamol and BDP was
      superior to salbutamol alone. Treatment with only bronchodilators results in a
      poor control of asthma and therefore, these should always be combined with
      inhaled steroids.

PMID- 7737700
TI  - Nasal mucus clearance in chronic smokers.
AB  - Smokers were observed to have grossly prolonged nasal mucus clearance. It was
      also inferred that the persons smoking bidi/unfiltered cigarettes had significant
      depression of ciliary activity. The clearance was prolonged as the number of
      cigarettes smoked and the duration of smoking increased. It was greater among
      those who gave a history of nasal exhalation of inhaled smoke. Nasal mucociliary
      clearance measurement is easy to measure and can be a useful index in evaluating
      the effect of smoking on the ciliary activity of the mucosa of the respiratory
      tract.

PMID- 7737701
TI  - Multi drug resistant tuberculosis.

PMID- 7737702
TI  - Intra pulmonary thrombolytic therapy with balloon dilatation in recurrent acute
      pulmonary embolism.
AB  - A 52-year-old man had recurrent pulmonary thrombo embolism following fracture in
      tibia and subsequent deep vein thrombosis. One episode of massive pulmonary
      embolism with haemodynamic compromise was managed successfully by balloon
      compression of the thrombus and thrombolysis with urokinase. Patient was
      rehabilitated in his previous profession.

PMID- 7737703
TI  - Resolution of cryptococcal meningitis and associated granuloma lung with
      antifungal therapy: report of a case.
AB  - A 49-year-old diabetic male had been unsuccessfully treated with antitubercular
      therapy for a granulomatous lesion of the left lung detected elsewhere nine
      months ago. He presented with evidence of meningitis which was found to be due to
      infection with Cryptococcus neoformans. Both the meningeal and lung lesions
      resolved after 6 weeks of combined therapy with amphotericin B and flucytosine.
      The report of the case along with a brief review of the relevant literature is
      presented.

PMID- 7737704
TI  - Pleural effusion due to lymphatic filariasis.
AB  - A case of pleural effusion is reported. Pleural biopsy showed microfilariae on
      histopathological examination. Treatment with diethyl carbamazine yielded
      excellent results. Filarial aetiology should be included in the differential
      diagnosis of idiopathic pleural effusions, especially in endemic areas.

PMID- 7737705
TI  - A case of bilateral pulmonary hydatid cysts.
AB  - A case of bilateral hydatid lung disease is reported who presented with a history
      of short duration and large opacities in both lung fields. A trial of medical
      treatment with albendazole 400 mg BD for 6 weeks failed. The patient was managed
      by surgical intervention which also ultimately established the diagnosis of
      hydatid disease.

PMID- 7737706
TI  - Role of bradykinin in insulin sensitivity and blood pressure regulation during
      hyperinsulinemia.
AB  - The purpose of these experiments was to determine in normotensive rats the role
      of endogenous bradykinin, prostaglandins, and nitric oxide in glucose metabolism
      and blood pressure response to hyperinsulinemia. Normotensive Wistar rats were
      treated with two different bradykinin antagonists, indomethacin or N omega-nitro
      L-arginine methyl ester, concurrently with a euglycemic clamp with insulin
      infusion rates of 3 or 6 mU/kg per minute. Glucose uptake, steady-state plasma
      insulin levels, and insulin sensitivity index were determined over 2 hours.
      Bradykinin inhibition dramatically reduced glucose uptake and insulin sensitivity
      index during both the lower and higher insulin infusion rates to 30% and 32%,
      respectively, of values observed in control rats. Inhibition of prostaglandins or
      nitric oxide did not alter glucose metabolism in these rats. Blood pressure
      remained unchanged in the control group throughout the clamp but increased
      significantly in rats submitted to inhibition of bradykinin, prostaglandins, or
      nitric oxide, suggesting that these vasodilator systems tend to counteract the
      hypertensive effect of hyperinsulinemia. The counterregulatory component
      attributable to bradykinin was about twice as great as that attributable to
      nitric oxide. These findings suggest that insulin infusion in normotensive Wistar
      rats fails to raise blood pressure because its effects are offset by mobilization
      of vasodilator mechanisms, such as bradykinin, prostaglandins, and nitric oxide.
      Bradykinin seems to play the most important homeostatic role under these
      conditions, because its inhibition significantly reduces insulin sensitivity and
      allows blood pressure to rise.

PMID- 7737707
TI  - Effect of inhibiting renal kallikrein on prostaglandin E2, water, and sodium
      excretion.
AB  - To test the hypothesis that renal kinins act as natriuretic and diuretic
      hormones, we examined the effect of inhibiting glandular kallikrein on renal
      function in normotensive unanesthetized rats during normal sodium intake. To
      inhibit kallikrein at both the luminal and basolateral sides of the distal
      nephron, we used Fab fragments of monoclonal antibodies to rat urinary kallikrein
      (Fab-kallikrein). Fab fragments have advantages over intact IgG: they are
      filtered through the glomerulus and reach the lumen of the distal nephron, where
      kallikrein is localized and urinary kinins are released. Furthermore, the Fab
      fragment-antigen complex does not activate the complement system, avoiding the
      side effects associated with intact antibodies. Fab-kallikrein effectively
      blocked generation of kinins in the nephron lumen, decreasing urinary
      kininogenase activity (kallikrein) by 74% to 85% and kinin excretion by 76% to
      79%. Fab-kallikrein induced a 30% decrease in urine volume and a 20% to 40%
      decrease in urinary sodium excretion but did not alter blood pressure, glomerular
      filtration rate, or renal blood flow. Although urinary prostaglandin E2 excretion
      also tended to decrease, this change was slower and of lesser magnitude than
      those of kinin and kininogenase excretion and did not attain statistical
      significance after Bonferroni's correction. In controls injected with either
      vehicle or Fab fragments of monoclonal antibodies to ricin (a vegetable protein
      not present in mammals), none of these parameters decreased significantly. We
      conclude that renal kinins participate in the short-term regulation of water and
      sodium excretion in normotensive unanesthetized rats, acting as diuretic and
      natriuretic hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737708
TI  - Angiotensin and bradykinin peptides in the TGR(mRen-2)27 rat.
AB  - The transgenic TGR(mRen-2)27 rat, in which the Ren-2 mouse renin gene is
      transfected into the genome of the Sprague-Dawley rat, develops severe
      hypertension at a young age that responds to inhibitors of angiotensin-converting
      enzyme and to antagonists of the type 1 angiotensin II (Ang II) receptor. Despite
      this evidence that the hypertension is Ang II dependent, TGR(mRen-2)27 rats have
      suppressed renal renin and renin mRNA content, and there is controversy
      concerning the plasma levels of renin and Ang II in these rats. We investigated
      the effect of the transgene on circulating and tissue levels of angiotensin and
      bradykinin peptides in 6-week-old male homozygous TGR(mRen-2)27 rats. Systolic
      blood pressure of TGR(mRen-2)27 rats was 212 +/- 4 mm Hg (mean +/- SEM, n = 25)
      compared with 108 +/- 2 mm Hg (n = 29) for age- and sex-matched Sprague-Dawley
      rats. Compared with control rats, TGR(mRen-2)27 rats had increased plasma levels
      of active renin (4.5-fold), prorenin (300-fold), and Ang II (fourfold) as well as
      tissue levels of Ang II (twofold to fourfold in kidney, adrenal, heart, aorta,
      brown adipose tissue, and lung and 18-fold in brain). Plasma angiotensinogen
      levels were reduced to 73% of control, and plasma aldosterone levels were
      increased fourfold. Plasma angiotensin-converting enzyme was reduced to 64% of
      control. Compared with control rats, TGR(mRen-2)27 rats had increased bradykinin
      levels in brown adipose tissue (1.9-fold) and lung (1.6-fold).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7737709
TI  - Renal interstitial fluid angiotensin. Modulation by anesthesia, epinephrine,
      sodium depletion, and renin inhibition.
AB  - Using a microdialysis technique, we monitored changes in right and left renal
      interstitial fluid angiotensins in anesthetized and conscious dogs (both n = 5)
      in response to right renal interstitial epinephrine (0.2 mg/kg per minute)
      administration. Renal interstitial and plasma angiotensin levels also were
      monitored in conscious dogs (n = 4) in response to dietary sodium deprivation (10
      mmol/d) for 5 consecutive days. Changes in renal interstitial and plasma
      angiotensins in response to interstitial administration of a specific renin
      inhibitor, ACRIP (0.5 micrograms/kg per minute for 20 minutes), were monitored on
      day 5 of sodium depletion. At basal levels, there were no significant differences
      between the right and left renal interstitial immunoreactive angiotensin levels
      in anesthetized dogs. Renal interstitial epinephrine administration caused a
      significant increase in renal interstitial immunoreactive angiotensin
      concentrations in both anesthetized and conscious dogs (P < .01). However,
      anesthetized dogs had significantly higher renal interstitial immunoreactive
      angiotensin levels basally and in response to epinephrine than conscious dogs (P
      < .05). Renal interstitial immunoreactive angiotensin concentrations increased
      significantly and progressively during exposure to a low sodium diet from 3.9 +/-
      1 nmol on day 1 to 740 +/- 332 nmol on day 5 (P < .01). Renal interstitial
      immunoreactive angiotensin decreased significantly to 124 +/- 37 nmol (P < .01)
      in response to intrarenal renin inhibition at the end of day 5 of sodium
      depletion. Plasma immunoreactive angiotensin increased significantly (P < .01) in
      response to sodium depletion, and no change occurred during intrarenal renin
      inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737710
TI  - Role of endogenous endothelins in the renin system of normal and two-kidney, one
      clip rats.
AB  - This study aimed to investigate the relevance of endogenous endothelins in the
      control of renin secretion and renin gene expression under basal conditions and
      stimulated conditions achieved with unilateral renal artery stenosis. To this
      end, we studied the effects of the orally active endothelin antagonist Ro 47-0203
      (100 mg/kg per day) for 2 days on plasma renin activity and renal renin mRNA
      levels in normal rats and rats with unilateral renal artery clips (0.2 mm).
      Treatment with Ro 47-0203 did not change basal arterial pressure but
      significantly attenuated the rise of blood pressure in response to renal artery
      clipping. Although Ro 47-0203 tended to increase basal plasma renin activity,
      this effect was not significant. Basal renin mRNA levels of kidneys were also not
      changed by the drug. Unilateral renal artery clipping increased plasma renin
      activity from 12 to 34 ng angiotensin I/mL per hour, increased renin mRNA levels
      to 328% of controls in the clipped kidneys, and decreased renin mRNA levels to
      23% of controls in the contralateral intact kidneys. These changes were not
      influenced by Ro 47-0203. In isolated perfused rat kidneys, Ro 47-0203 (10
      mumol/L) also had no effect on basal renin secretion or vascular resistance, but
      it substantially attenuated the decrease of renin secretion and renal flow in
      response to administration of exogenous endothelin. Taken together, these
      findings suggest that endogenous endothelins play no relevant role in the control
      of renin secretion and of renin gene expression in normal and hypoperfused rat
      kidneys.

PMID- 7737711
TI  - Identification of vasopressin mRNA in rat aorta.
AB  - We have reported previously that several blood vessels of the rat and cow contain
      immunoreactive vasopressin and further suggested that this peptide might be
      produced locally. To provide additional support for this hypothesis, we conducted
      the present study to determine whether mRNA for arginine vasopressin is also
      present in blood vessels. Ribonuclease protection analysis of total RNA isolated
      from rat hypothalamus and aorta revealed the presence of arginine vasopressin
      message in both tissues but not in RNA isolated from liver, a tissue devoid of
      vasopressin. Subsequent comparison of the autoradiographic intensities of the
      signals in these two tissues indicated that vasopressin message was 100- to 1000
      fold lower in aorta. Additional studies showed that RNA isolated from endothelium
      denuded vessels contained levels of arginine vasopressin message similar to those
      in intact vessels, indicating that endothelium was not a major source of this
      message. These data were substantiated by further studies using a vasopressin
      radioimmunoassay, which showed that vasopressin peptide levels in intact and
      endothelium-denuded vessels did not differ. Thus, the present study showed that
      rat aorta contains arginine vasopressin mRNA as well as the vasopressin peptide
      and that both the message and the peptide are contained in nonendothelial
      structures. However, the data do not rule out endothelium as a possible source of
      vasopressin. These studies add further support to the hypothesis that blood
      vessels are capable of producing vasopressin.

PMID- 7737712
TI  - Different effects of fosinopril and atenolol on wave reflections in hypertensive
      patients.
AB  - We conducted this study to compare the effects of fosinopril versus atenolol on
      peripheral blood pressure, central arterial wave reflection, and left ventricular
      mass in a group of patients with essential hypertension. We conducted a double
      blind, randomized trial of fosinopril and atenolol in 79 hypertensive patients
      (52 men, 27 women; mean age, 45.8 +/- 8.5 years; range, 30 to 68 years). Carotid
      pressure waveforms were recorded noninvasively by applanation tonometry with a
      Millar micromanometer-tipped probe. The extent of wave reflection was estimated
      by the augmentation index defined as the ratio of the amplitude of pressure wave
      above its systolic shoulder to the pulse pressure. The augmentation index, left
      ventricular mass index by two-dimensional echocardiography, and 24-hour
      ambulatory blood pressures were determined before and after 8 weeks of daily
      treatment with fosinopril (10 to 20 mg) or atenolol (50 to 100 mg) with or
      without diuretics and compared with those values in 79 normotensive control
      subjects. After 8 weeks of treatment, both drugs lowered 24-hour ambulatory
      peripheral systolic and diastolic pressures into the normal range to a similar
      extent (fosinopril, -18/-13 mm Hg; atenolol, -23/-17 mm Hg, both P = NS). On the
      other hand, whereas the elevated augmentation index in hypertensive patients
      compared with normotensive subjects (16 +/- 11% versus 10 +/- 8%) was completely
      normalized by fosinopril (-9.3 +/- 9.8%, P < or = .002), it was lowered by
      atenolol (-4.8 +/- 8.9%, P < .002) but to a significantly smaller extent
      (fosinopril versus atenolol effect, P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737713
TI  - Reduction of salt intake during converting enzyme inhibitor treatment compared
      with addition of a thiazide.
AB  - A moderate reduction in salt intake lowers blood pressure in individuals with
      hypertension and improves blood pressure control in those taking a converting
      enzyme inhibitor. However, it is unclear how effective reduction of salt intake
      is compared with addition of other drugs, in particular, thiazide diuretics. We
      directly compared the separate effects on blood pressure of reducing sodium
      intake or adding a thiazide diuretic in the pressure of a converting enzyme
      inhibitor in a double-blind, randomized, crossover study. We studied 11 subjects
      with essential hypertension who had been taking 25 mg captopril twice daily for
      at least 1 month. In the double-blind study, after 1 month of captopril alone,
      supine blood pressure was 151 +/- 5/95 +/- 4 (SEM) mm Hg. With the addition of 25
      mg hydrochlorothiazide once daily for 1 month, blood pressure fell to 137 +/-
      5/87 +/- 3 mm Hg. When a moderate reduction in salt intake (from 206 +/- 26 to
      109 +/- 20 mmol urinary sodium/24 h) was added to captopril for 1 month, blood
      pressure was reduced by a similar amount (to 137 +/- 4/90 +/- 3 mm Hg). Plasma
      potassium fell during the diuretic treatment (3.9 +/- 0.1 to 3.7 +/- 0.1 mmol/L,
      P < .05) but increased nonsignificantly during salt reduction (3.9 +/- 0.1 to 4.1
      +/- 0.2 mmol/L). These results clearly demonstrate that moderate salt reduction,
      which can be easily achieved, is as effective as a thiazide diuretic in lowering
      blood pressure in the presence of a converting enzyme inhibitor and has the
      particular advantage that plasma potassium does not decrease.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7737714
TI  - Trends in medication choices for hypertension in the elderly. The decline of the
      thiazides.
AB  - We studied the evolution in choice of antihypertensive therapy in the elderly
      over a seven-year period and defined factors associated with such prescribing. To
      accomplish this, we performed a retrospective analysis of 8428 enrollees older
      than 65 years of age in the New Jersey Medicaid and Medicare programs newly begun
      on antihypertensive therapy between 1982 and 1988. Diuretics were the most common
      agents prescribed (51%), followed by calcium channel blockers (14%), beta
      blockers (13%), central adrenergic antagonists (11%), and angiotensin-converting
      enzyme inhibitors (5%). However, the use of diuretics declined sharply during the
      latter part of the time interval studied. Using logistic regression modeling, we
      determined that the odds of a subject being started on a diuretic compared with
      any other antihypertensive drug decreased from 1.0 during the referent years 1982
      to 1984 to 0.75 in 1985 to 1986 and to 0.41 in 1987 to 1988, after controlling
      for demographics, comorbidity, and hospital and physician visits (P < .001). The
      relative odds of diuretic use were significantly increased (P < .05) for the
      oldest subjects (odds ratio, 1.28 for age 85 and older versus ages 65 to 74
      odds), women (odds ratio, 1.15), and blacks (odds ratio, 1.14). Despite the
      growing evidence during the study interval of the efficacy of diuretics in
      treating hypertension in the elderly, diuretic use diminished throughout this
      period in relation to other antihypertensive drugs. Subject characteristics
      (oldest subjects, women, and blacks) were important determinants of physicians'
      choice of antihypertensive therapy.

PMID- 7737715
TI  - Thiazides and hypertension in the elderly.

PMID- 7737716
TI  - Cardiovascular effects of brain natriuretic peptide in essential hypertension.
AB  - We evaluated the cardiovascular effects of pathophysiological plasma levels of
      brain natriuretic peptide in seven patients with mild to moderate essential
      hypertension by performing equilibrium radionuclide angiocardiography at baseline
      and during brain natriuretic peptide infusion at increasing doses (4, 8, 10, and
      12 pmol/kg per minute for 20 minutes each). Brain natriuretic peptide induced a
      progressive reduction of left ventricular end-diastolic volume (from 107.5 +/-
      10.3 to 89.0 +/- 11.0 mL at the end of all infusion periods) and end-systolic
      volume, whereas stroke volume did not show any significant change (from 64.9 +/-
      5.9 to 62.7 +/- 7.8 mL). Cardiac output, arterial pressure, and peripheral
      vascular resistance did not change significantly. The lack of effects on systemic
      hemodynamics was probably due to compensatory activation of the sympathetic
      nervous system, as indicated by the significant increase in plasma norepinephrine
      levels (from 1.75 +/- 0.18 to 2.19 +/- 0.21 nmol/L), heart rate (from 68 +/- 6 to
      81 +/- 6 beats per minute), peak ejection rate, and peak filling rate. These
      results indicate that brain natriuretic peptide, at the pathophysiological plasma
      concentrations reached in this study, influences cardiovascular homeostasis
      mainly by reducing cardiac preload.

PMID- 7737717
TI  - Spontaneous cardiac baroreflex in humans. Comparison with drug-induced responses.
AB  - We compared two methods of assessment of baroreflex sensitivity in eight supine
      healthy volunteers during repeated baseline measurements and various conditions
      of cardiac autonomic blockade. The spontaneous baroreflex method involved
      computer scanning of recordings of continuous finger arterial pressure and
      electrocardiogram to locate sequences of three or more beats in which pressure
      spontaneously increased or decreased, with parallel changes in pulse intervals.
      The mean regression slope of all these sequences during each study condition was
      considered to represent the mean spontaneous baroreflex slope. In the drug
      induced method, sigmoidal curves were constructed from data obtained by bolus
      injections of phenylephrine and nitroprusside; the tangents taken at the resting
      pressure of each of these curves were compared with the mean spontaneous
      baroreflex slopes. The two methods yielded slopes that were highly correlated (r
      = .96, P < .001), with significant but similar intraindividual baseline
      variability. Atropine virtually eliminated the baroreflex slope; subsequent
      addition of propranolol did not alter it further. Propranolol or clonidine alone
      increased average baroreflex slope to the extent that they increased resting
      pulse interval (r = .69 to .83). The spontaneous baroreflex method provides a
      reliable, noninvasive assessment of human vagal cardiac baroreflex sensitivity
      within its physiological operating range.

PMID- 7737718
TI  - Cerebral ATP-sensitive potassium channels during acute reduction of carotid blood
      flow.
AB  - The ATP-sensitive potassium channels (KATP) are activated either by a decrease in
      intracellular ATP content or by a lowering of the ATP-ADP ratio such as during
      stroke. We studied the role of cerebral KATP on arterial pressure during acute
      reduction of cerebral blood flow in 12-week-old male Wistar rats anesthetized
      with urethane by recording arterial pressure and heart rate continuously. After
      bilateral ligation of the common carotid arteries, glibenclamide, a specific
      blocker of KATP, was injected intracerebroventricularly into the cerebral lateral
      ventricle. Glibenclamide elicited a sustained vasopressor response in a dose
      dependent manner in rats with bilateral carotid artery ligation (10 nmol, +15 +/-
      2 mm Hg; 1 nmol, +5 +/- 1 mm Hg, P < .01 versus vehicle), but hemodynamic
      alterations were barely recorded with glibenclamide in sham-operated control
      rats. The abdominal sympathetic discharge was not increased significantly enough
      to explain the pressor mechanism. Similarly, pretreatments with intravenous
      injections of bunazosin, an alpha 1-adrenoceptor antagonist, did not affect the
      pressor response of intracerebroventricular glibenclamide. To investigate the
      vasopressor mechanism further, we measured plasma and pituitary concentrations of
      arginine vasopressin and determined the effects of vasopressin receptor
      antagonists. The intracerebroventricular injections of glibenclamide
      significantly increased the plasma concentration of vasopressin (P < .05) and
      significantly decreased the pituitary concentration of vasopressin (P < .05) in
      rats with bilateral carotid artery ligation. Intravenous pretreatment with the
      vasopressin V1 receptor antagonist OPC-21268 abolished the vasopressor response
      to intracerebroventricular glibenclamide (+16 +/- 2 versus +1 +/- 1 mm Hg, P <
      .01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737719
TI  - Effects of bromocriptine on cardiovascular regulation in healthy humans.
AB  - Bromocriptine, a dopamine agonist with central nervous system actions, may reduce
      sympathetic nervous system activity. We tested this hypothesis by measuring
      arterial blood pressure, central venous pressure, heart rate, muscle sympathetic
      nerve activity, and forearm blood flow before and after unloading the arterial
      baroreceptors with sodium nitroprusside (0.5 to 1.5 mcg/kg per minute IV), before
      and after unloading the cardiopulmonary baroreceptors with incremental lower body
      negative pressure (0 to -15 mm Hg), and before and after immersion of the hand in
      ice-cold water for 2 minutes (cold pressor test). After obtaining basal responses
      to provocative maneuvers, we gave 20 healthy subjects either 5 mg oral
      bromocriptine (n = 10) or placebo (n = 10) in a randomized, double-blind fashion.
      Bromocriptine did not affect resting mean arterial pressure, heart rate, or
      forearm blood flow. Bromocriptine decreased resting central venous pressure by
      1.2 mm Hg (P < .05) and tended to increase total integrated muscle sympathetic
      nerve activity (from 151 +/- 44 to 212 +/- 82 U/min, P = NS). The reflex
      increases in muscle sympathetic nerve activity to nitroprusside infusion and
      lower body negative pressure were unchanged by bromocriptine; however, vascular
      responsiveness to both maneuvers was impaired after bromocriptine administration
      compared with control. Without bromocriptine, the reflex increase in muscle
      sympathetic nerve activity after nitroprusside-induced hypotension maintained
      forearm blood flow at a constant level, whereas with bromocriptine the forearm
      blood flow increased from 1.9 +/- 0.3 to 2.8 +/- 0.6 mL/min per 100 mL (P <
      .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737720
TI  - In vivo evidence for microvascular oxidative stress in spontaneously hypertensive
      rats. Hydroethidine microfluorography.
AB  - The factors that predispose to the accelerated organ injury that accompanies the
      hypertensive syndrome have remained speculative and without a firm experimental
      basis. Indirect evidence has suggested that a key feature may be related to an
      enhanced oxygen radical production. The purpose of this study was to refine and
      use a technique to visualize evidence of spontaneous microvascular oxidative
      stress in vivo in the spontaneously hypertensive rat (SHR) compared with its
      normotensive control, the Wistar-Kyoto rat (WKY). We investigated the effects of
      adrenal glucocorticoids on the microvascular oxidative stress sequence. The
      mesentery was superfused with hydroethidine, a reduced, nonfluorescent precursor
      of ethidium bromide. In the presence of oxidative challenge, hydroethidine is
      transformed intracellularly into the fluorescent compound ethidium bromide, which
      binds to DNA and can be detected by virtue of its red fluorescence. The
      fluorescent light emission from freshly exteriorized and otherwise unstimulated
      mesentery microvessels was recorded by digital microscopy. The number of ethidium
      bromide-positive nuclei along the arteriolar and venular walls in SHR was found
      to be significantly increased above the level exhibited by WKY. The elevation in
      ethidium bromide fluorescence in SHR arterioles could be attenuated by a
      synthetic glucocorticoid inhibitor and in rats subjected to adrenalectomy. The
      administration of glucocorticoids after adrenalectomy by injection of
      dexamethasone restored the oxidative reaction in SHR arterioles. Treatment with
      dimethylthiourea and with a xanthine oxidase inhibitor attenuated the superoxide
      formation. Although a nitric oxide synthase inhibitor (NG-nitro-L-arginine methyl
      ester) enhanced the ethidium bromide staining in WKY, it did not affect that in
      SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737721
TI  - Nitroxidergic innervation in dog and monkey renal arteries.
AB  - We analyzed mechanisms underlying neurogenic vasodilatation in dog and Japanese
      monkey renal arteries. Isometric mechanical responses of the arterial strip to
      nerve stimulation by nicotine were recorded. Nicotine-induced contractions were
      abolished by hexamethonium and potentiated by NG-nitro-L-arginine, a nitric oxide
      synthase inhibitor. The potentiating effect was reversed by L-arginine. NG-Nitro
      L-arginine did not potentiate the contraction caused by norepinephrine. The
      nicotine-induced contraction was reversed to a relaxation by prazosin. The
      relaxation was not influenced by indomethacin, timolol, or atropine but was
      abolished by NG-nitro-L-arginine, methylene blue (a guanylate cyclase inhibitor),
      oxyhemoglobin (a nitric oxide scavenger), and hexamethonium. In the strips
      treated with NG-nitro-L-arginine, the nicotine-induced relaxation was restored by
      L-arginine. Histochemical study demonstrated perivascular nerves containing NADPH
      diaphorase and nitric oxide synthase immunoreactivity in dog and monkey arteries.
      We conclude that renal arteries are innervated by nitric oxide-mediated
      vasodilator and adrenergic vasoconstrictor nerves, and depression of the
      vasodilator nerve function by nitric oxide synthase inhibition potentiates the
      contraction caused by adrenergic nerve excitation.

PMID- 7737722
TI  - Effect of circulating epinephrine on platelet function and hematocrit.
AB  - We investigated the effect of raising arterial plasma epinephrine within the
      lower pathophysiological concentration range on various indicators of blood
      platelet function and hematocrit. Epinephrine was raised over 60 minutes by a
      stepwise increasing intravenous infusion in 40 healthy men aged 20 to 40 years.
      Platelet count increased progressively with increasing arterial epinephrine to a
      maximal change of 69 +/- 6 x 10(9)/L in EDTA-anticoagulated blood and a maximal
      change of 42 +/- 6 x 10(9)/L in acid-citrate-dextrose (ACD)-anticoagulated blood,
      and the weight of circulating platelets increased by 29% (P < .001). Platelet
      size increased significantly in EDTA and decreased in ACD, and the difference
      between EDTA and ACD was significant (P < .0001) for both count and size,
      suggesting that epinephrine not only recruits platelets into the circulation but
      also induces some microaggregation in vivo or adhesion ex vivo. Aggregation of
      platelets in vitro induced by epinephrine decreased (P < .003 for delta optical
      density and P = .038 for maximal optical density) after epinephrine infusion
      compared with saline but did not change when stimulated with ADP or collagen.
      These findings suggest a selective downregulation of the epinephrine-activating
      mechanisms concomitant with a rise in the platelet content of epinephrine by 81%
      (P < .001) and no change in the platelet sodium-proton membrane exchange. The
      release of granular content (beta-thromboglobulin and platelet factor 4) to the
      circulation in response to epinephrine was not significant. Thus, under acute
      conditions it seems that the platelets may protect themselves against
      inappropriate overstimulation by epinephrine. The importance of platelet
      epinephrine uptake is still unknown, but sodium-proton exchange does not seem to
      be involved in regulating the effects of circulating epinephrine on platelet
      function. Epinephrine has a pronounced effect on raising hematocrit (maximal
      change of 1.74 +/- 0.13 x 10(-2), P < .0001).

PMID- 7737723
TI  - Relationship of alcohol intake with blood pressure in young adults.
AB  - The objective of this study was to examine the relationship of usual current
      alcohol intake with systolic and diastolic pressures among young adults.
      Participants were 316 men and women, aged 18 to 26 years, from East Boston, Mass.
      At each of three weekly visits we obtained three blood pressure measurements on
      each subject using a random-zero sphygmomanometer. Using an interviewer
      administered questionnaire, we obtained information about quantity and frequency
      of alcohol intake during the previous month. The lowest systolic pressure levels
      were in subjects consuming 1 to < 2 drinks per day. Adjusted for age, sex, and
      body mass index, systolic pressure was higher by 4.0 mm Hg (95% confidence
      interval [CI], 0.5 to 7.6 mm Hg) in abstainers, 3.6 mm Hg (95% CI, 0.5 to 6.6 mm
      Hg) in those who drank < 1 drink per day, 0.4 mm Hg (95% CI, -4.7 to 5.5 mm Hg)
      in those who drank 2 to < 3 drinks per day, and 8.1 mm Hg (95% CI, 2.9 to 13.4 mm
      Hg) in those who drank > or = 3 drinks per day. Levels of diastolic pressure were
      lowest in those consuming 2 to < 3 drinks per day. Adjustment for pulse rate,
      smoking, medication use, and family history of hypertension did not alter the
      results. These results suggest a J-shaped association of alcohol intake with
      blood pressure level in young adults, with the lowest levels in consumers of 1 to
      3 drinks per day.

PMID- 7737725
TI  - Ambulatory blood pressure.

PMID- 7737724
TI  - A noninvasive computerized tail-cuff system for measuring blood pressure in mice.
AB  - We have validated a noninvasive computerized tail-cuff system for measuring blood
      pressure in mice. The system was designed to perform all functions automatically,
      including a programmable routine of cuff inflation and deflation, analysis and
      assignment of pulse rate and blood pressure, and recording of data
      electronically. To evaluate this system over a range of blood pressures, we gave
      groups of mice enalapril or NG-nitro-L-arginine methyl ester in their drinking
      water. For each of these groups, an equal number of control mice were given
      nothing in their drinking water. Tail-cuff blood pressures were recorded as the
      means of blood pressures determined on at least 3 days after at least 7 days of
      training. Tail-cuff enalapril and control group means were measured both 3 and 4
      months after enalapril (or no drug) was begun; the group means at 3 months were
      not significantly different from the group means at 4 months. These results
      demonstrate that the system gives reproducible results. After the tail-cuff
      measurements were completed, intra-arterial blood pressures were attempted in all
      mice under unrestrained, unanesthetized conditions, and individual mouse (n = 22)
      blood pressures with the use of the two methods were compared. The blood
      pressures from individual mice by tail-cuff and intra-arterial methods were
      highly correlated (r = .86, P < .01). The means for the four mouse groups were
      also highly correlated (r = .98, P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737726
TI  - Angiotensin II increases vascular permeability factor gene expression by human
      vascular smooth muscle cells.
AB  - Angiotensin II (Ang II) has been implicated in the pathogenesis of the vascular
      injury associated with hypertension and diabetes mellitus. Increased vascular
      permeability is an important early manifestation of endothelial dysfunction and
      the pathogenesis of atherosclerosis. How Ang II contributes to endothelial
      dysfunction and promotes an increase in vascular permeability is unknown but is
      classically attributed to its pressor actions. We demonstrate that human vascular
      smooth muscle cells express abundant mRNA for vascular permeability/endothelial
      growth factor. Vascular permeability factor is a 34- to 42-kD glycoprotein that
      markedly increases vascular endothelial permeability and is a potent endothelial
      mitogen. Ang II potently induced a concentration-dependent (maximal, 10(-7)
      mol/L) and time-dependent increase in vascular permeability factor mRNA
      expression by human vascular smooth muscle cells that was maximal after 3 hours
      and diminished by 24 hours. Ang II-induced vascular permeability factor mRNA
      expression by human vascular smooth muscle cells was inhibited by the specific
      Ang II receptor antagonist losartan (DuP 753), confirming that this is an Ang II
      receptor subtype 1-mediated event. These results describe a new action of Ang II
      on human vascular smooth muscle, notably the induction of vascular permeability
      factor mRNA expression. The wide spectrum and potent activity of vascular
      permeability factor suggest a novel mechanism whereby Ang II could locally and
      directly influence the permeability, growth, and function of the vascular
      endothelium independent of changes in hemodynamics.

PMID- 7737727
TI  - Measuring forearm blood flow and interpreting the responses to drugs and
      mediators.
AB  - Venous occlusion plethysmography has been widely used to study forearm blood
      flow. The principle of the technique is straightforward: the rate of swelling of
      the forearm during occlusion of venous return is used to assess the rate of
      arterial inflow. Provided that perfusion pressure (arterial blood pressure)
      remains constant, changes in flow reflect changes in smooth muscle tone in small
      arteries and arterioles. Local infusion into the brachial artery allows
      assessment of the direct effect of drugs on vascular tone and has been used to
      probe the roles of endogenous mediators. The technique is at its most powerful
      when dose-response relationships to different drugs or mediators within a single
      study are being compared but can also be used for comparison of responses to
      drugs between healthy control subjects and patient populations. However, when
      responses between groups are being compared, it is important to take into account
      the starting conditions of baseline blood flow and pressure. This article
      describes venous occlusion plethysmography, discusses the presentation and
      analysis of data (dose of drug or concentration? forearm blood flow or
      resistance?), and highlights certain potential problems and limitations of the
      technique as a means of studying disease states.

PMID- 7737728
TI  - Proposed update of angiotensin receptor nomenclature.

PMID- 7737729
TI  - Angiotensin peptides in spontaneously hypertensive and normotensive Donryu rats.
AB  - The renin-angiotensin system has been implicated in the pathogenesis of
      hypertension in spontaneously hypertensive rats (SHR). Given that SHR may have
      normal or suppressed plasma levels of renin and angiotensin peptides, we examined
      whether the tissue levels of angiotensin peptides are elevated in these rats. We
      measured angiotensin-(1-7) [Ang-(1-7)], Ang II, and Ang I in plasma, kidney,
      adrenal, heart, aorta, brown adipose tissue, lung, and brain of male SHR and
      normotensive Donryu rats at 6, 10, and 20 weeks of age. SHR had higher blood
      pressures and ratios of heart weight to body weight at all ages. Plasma renin
      levels of SHR were 13% to 32% of the levels of Donryu rats. Although plasma
      angiotensin-converting enzyme activity was lower in SHR than in Donryu rats, lung
      was the only SHR tissue with a reduced Ang II-Ang I ratio. Ang II levels in SHR
      adrenal were 24% to 42% of the levels of Donryu adrenal, and for SHR plasma,
      aorta, brown adipose tissue, and lung, Ang II levels were 38% to 93% of the
      levels of Donryu rats. For kidney and heart, Ang II levels were similar in SHR
      and Donryu rats at 6 weeks of age although suppressed in SHR at 10 and 20 weeks.
      Moreover, brain Ang II levels were higher in SHR than Donryu rats at 6 weeks of
      age and similar at 10 and 20 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737730
TI  - Intrarenal angiotensin II formation in humans. Evidence from renin inhibition.
AB  - The intrarenal production of angiotensin II (Ang II) as a local hormone,
      suggested by multiple lines of investigation, has been difficult to buttress with
      evidence of functional significance in humans. During studies designed to assess
      the renal vascular responses to the renin inhibitor enalkiren, an agent (like
      others in its class) with great substrate specificity, we noted in some subjects
      that the time course of the effect of enalkiren on renal plasma flow was not
      congruent with the time course of its influence on the renin-angiotensin system
      in the plasma compartment. We pursued this discrepancy in the current study of 18
      healthy men and 9 men with essential hypertension, who each received one or more
      doses of enalkiren while on a fixed sodium diet. Plasma enalkiren and Ang II
      concentration and renal plasma flow were measured in each subject at intervals
      during and after discontinuation of the enalkiren infusion. Plasma enalkiren
      concentration fell progressively in each subject after administration was
      discontinued, the fall becoming evident 10 minutes after discontinuation without
      exception. In plasma samples obtained 90 minutes after the end of the infusion,
      drug levels were generally less than half of their peak value. Plasma Ang II
      concentration, at nadir levels by the end of the enalkiren administration, rose
      consistently during recovery. Renal plasma flow, in contrast, rose during
      infusion but did not begin to fall when enalkiren was discontinued.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7737731
TI  - Hypertension induced by chronic renal adrenergic stimulation is angiotensin
      dependent.
AB  - We designed these studies to assess the role of the renin-angiotensin system in
      mediating the hypertensive and renal functional effects of chronic renal
      adrenergic stimulation. Norepinephrine was infused at 0.1 microgram/kg per minute
      for 7 days directly into the renal artery of uninephrectomized dogs under control
      conditions (n = 5) or after plasma angiotensin II (Ang II) concentration was
      fixed at control levels (n = 5) by chronic intravenous infusion of captopril (14
      micrograms/kg per minute) and Ang II (0.58 +/- 0.04 ng/kg per minute). During the
      first 60 minutes of norepinephrine infusion in control dogs, mean arterial
      pressure increased 9 +/- 4 mm Hg in association with a twofold to threefold rise
      in plasma renin activity. Additionally, glomerular filtration rate, renal plasma
      flow, sodium excretion, and fractional sodium excretion decreased to 70 +/- 5%,
      64 +/- 5%, 31 +/- 4%, and 38 +/- 6% of control, respectively, while filtration
      fraction increased 15 +/- 2%. In contrast to the pronounced short-term effects of
      norepinephrine on renal function, during chronic norepinephrine infusion, all
      indexes of renal function returned to control levels. However, elevations in both
      plasma renin activity and mean arterial pressure were sustained and on day 7 were
      2.3 +/- 0.6 ng angiotensin I/mL per hour (control, 0.5 +/- 0.1) and 110 +/- 7 mm
      Hg (control, 90 +/- 3). In dogs with fixed plasma levels of Ang II, acute and
      chronic changes in renal function induced by norepinephrine were similar to those
      in control dogs except that acute reductions in glomerular filtration rate tended
      to be more severe, and changes in filtration fraction and fractional sodium
      excretion were either attenuated or abolished. Moreover, in the absence of a rise
      in plasma Ang II concentration, mean arterial pressure did not change either
      acutely or chronically during norepinephrine infusion. These findings suggest a
      critical role for Ang II in mediating the hypertension associated with elevated
      levels of renal adrenergic stimulation that have little or no long-term effect on
      renal blood flow.

PMID- 7737732
TI  - Enhanced predictability of myocardial infarction in Japanese by combined genotype
      analysis.
AB  - To explore the genes responsible for myocardial infarction and restenosis after
      percutaneous transluminal coronary angioplasty, we performed association studies
      of the polymorphisms of the angiotensinogen and angiotensin-converting enzyme
      (ACE) genes. In the first study, normotensive myocardial infarction patients (n =
      103) and control subjects (n = 103), who were matched for established risk
      factors with the myocardial infarction patients, were randomly selected. The
      angiotensinogen-TT genotype (T indicates threonine instead of methionine at
      position 235) was more frequent in the myocardial infarction group than in the
      control group (P < .05). The ACE-DD genotype (D indicates a deletion polymorphism
      in intron 16) was also more frequent in the myocardial infarction group (P <
      .0001). The odds ratio estimated by the combined analysis of the angiotensinogen
      TT and ACE-DD genotypes (11.2) was markedly increased compared with that
      estimated separately from the angiotensinogen-TT (1.75) or ACE-DD (4.43)
      genotype. In the second study, we investigated 91 consecutive patients with acute
      myocardial infarction who underwent successful direct angioplasty. Combined
      analysis showed that the angiotensinogen-TT genotype did not enhance the
      predictability of myocardial infarction from the ACE-DD genotype. In conclusion,
      the angiotensinogen-TT genotype is a predictor for myocardial infarction, as well
      as the ACE-DD genotype, and the combined analysis of the angiotensinogen-TT and
      ACE-DD genotypes further enhanced the predictability of myocardial infarction in
      Japanese, suggesting its future clinical usefulness.

PMID- 7737733
TI  - Treatment in hypertensive cardiac hypertrophy, I. Neuropeptide Y and beta
      adrenoceptors.
AB  - In the present study, we investigated serum and myocardial neuropeptide Y
      concentrations as measures of sympathetic activity as well as myocardial beta
      adrenoceptors and beta-adrenoceptor-stimulated adenylyl cyclase activity in
      spontaneously hypertensive rats (SHR). SHR and control rats at 10 weeks of age
      were kept on oral treatment with captopril, nitrendipine, or both for 20 weeks.
      Treatment only slightly reduced but did not normalize blood pressure and cardiac
      hypertrophy in SHR. The elevated serum concentration of neuropeptide Y, the
      reduced number of beta-adrenoceptors, and the depressed beta-adrenoceptor
      stimulated adenylyl cyclase activity were partly normalized compared with the
      values observed in control rats. We conclude that antihypertensive treatment, at
      doses that failed to normalize systolic pressure and to reverse cardiac
      hypertrophy completely, is able to reduce sympathetic activity in SHR, thereby
      resensitizing the depressed beta-adrenoceptor-adenylyl cyclase system.

PMID- 7737734
TI  - Treatment in hypertensive cardiac hypertrophy, II. Postreceptor events.
AB  - We investigated the effect of pharmacological treatment with captopril,
      nitrendipine, and captopril plus nitrendipine on myocardial heterologous adenylyl
      cyclase desensitization and the underlying postreceptor defects in spontaneously
      hypertensive rats (SHR). In myocardial membranes from SHR, stimulation of
      adenylyl cyclase with guanylylimido-diphosphate (P < .001) and forskolin (P <
      .05) was significantly reduced, whereas no difference with forskolin was obtained
      in the presence of manganese chloride. Reconstitution of Gs alpha into Gs alpha
      deficient S49 cyc- mouse lymphoma cells revealed no difference between SHR and
      control rats. In contrast, pertussis toxin labeling of Gi alpha was significantly
      increased in SHR. The reduction of adenylyl cyclase in SHR was abolished after
      pertussis toxin treatment of membranes. Treatment with captopril, nitrendipine,
      or both reduced Gi alpha and increased guanylylimidodiphosphate-stimulated
      adenylyl cyclase activity in SHR. In summary, heterologous adenylyl cyclase
      desensitization due to an increase of Gi alpha but in the presence of an
      unchanged activity of Gs alpha or the catalyst occurs in SHR. This alteration,
      which could contribute to the progression of contractile dysfunction by producing
      adrenergic subsensitivity, is sensitive to pharmacological treatment most likely
      because of a reduction of sympathetic activity.

PMID- 7737735
TI  - Na(+)-H+ antiporter phenotype, abundance, and phosphorylation of immortalized
      lymphoblasts from humans with hypertension.
AB  - Previous studies have demonstrated an elevated Na(+)-H+ exchanger activity in
      various cell types from patients with essential hypertension. The phenotype of an
      increased maximal transport capacity is preserved in Epstein-Barr virus
      immortalized lymphoblasts from hypertensive patients. The mechanisms underlying
      this abnormality are unclear. In this study, we used lymphoblasts from
      hypertensive patients and normotensive control subjects with and without a family
      history of hypertension to determine (1) Na(+)-H+ exchanger activity using
      fluorometry with the pH indicator 2',7'-bis(carboxyethyl)-5(6)
      carboxyfluorescein, (2) Na(+)-H+ exchanger isoform 1 abundance with specific
      polyclonal antibodies, and (3) Na(+)-H+ exchanger phosphorylation by
      immunoprecipitation of the 32P-labeled transporter. Na(+)-H+ exchanger activity
      (in millimoles per liter per minute) measured when pHi was clamped at 6.0 was
      significantly higher in cells from hypertensive patients (18.8 +/- 0.6, P < .001)
      and those subjects with a family history of hypertension (16.4 +/- 0.6, P < .001)
      compared with normotensive control subjects (12.9 +/- 0.6). Exchanger abundance
      was identical in all three groups of subjects, indicating that increased activity
      in the hypertensive group was due to an elevated turnover number of the
      exchanger. Na(+)-H+ exchanger phosphorylation in quiescent cells was
      significantly elevated in cells from hypertensive patients (1.58 +/- 0.16, P <
      .001) compared with control subjects (1.00 +/- 0.07), and cells from normotensive
      subjects with a hypertensive family history showed intermediate values (1.23 +/-
      0.14). Identical changes in Na(+)-H+ exchanger function and phosphorylation have
      been demonstrated in vascular smooth muscle cells from spontaneously hypertensive
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737736
TI  - Na(+)-H+ exchange and essential hypertension. A new approach.

PMID- 7737737
TI  - Microalbuminuria and erythrocyte sodium-hydrogen exchange in essential
      hypertension.
AB  - Microalbuminuria (urinary albumin excretion between 20 and 200 micrograms/min)
      and abnormalities of red blood cell sodium-hydrogen exchange coexist in essential
      hypertensive patients. To evaluate how the two phenomena relate, we recruited 10
      untreated microalbuminuric male essential hypertensive patients without diabetes
      to be compared with an equal number of matched essential hypertensive patients
      excreting albumin in normal amounts as well as 10 healthy control subjects.
      Sodium-hydrogen exchange values were increased to a comparable extent in
      microalbuminuric and normoalbuminuric hypertensive patients. Systolic and mean
      blood pressures were higher in microalbuminuric patients. Fasting insulin was
      greater and high-density lipoprotein cholesterol lower in patients than control
      subjects. Urinary albumin excretion correlated positively with both mean blood
      pressure and left ventricular mass values in the absence of a relationship with
      circulating lipid and insulin levels. In contrast with microalbuminuria, sodium
      hydrogen exchange covaried only with high-density lipoprotein cholesterol and
      insulin levels. Thus, microalbuminuria and an abnormal sodium-hydrogen exchange
      are unrelated phenomena in essential hypertensive patients. Microalbuminuria
      appears to be a hemodynamically driven biological variable, while an accelerated
      sodium-hydrogen exchange seems primarily conditioned by the metabolic
      abnormalities of hypertension, possibly in the context of an insulin-resistant
      syndrome.

PMID- 7737738
TI  - Sodium-lithium countertransport has low affinity for sodium in hyperinsulinemic
      hypertensive subjects.
AB  - We recently reported that incubation of red blood cells with insulin markedly
      decreases the affinity for external Na+ and increases the maximal transport rate
      (Vmax) of Na(+)-Li+ countertransport. The association of hypertension with
      insulin resistance and its compensatory hyperinsulinemia led us to investigate
      the relationship between insulin levels in vivo and the Na+ activation kinetics
      of this antiporter. We studied normotensive (n = 28) and hypertensive (n = 25)
      subjects after they had fasted overnight and determined their plasma glucose and
      insulin concentrations. Insulin levels were higher in the hypertensive subjects
      (11.7 +/- 1.5 microU/mL, mean +/- SEM) than in the normotensive subjects (8.2 +/-
      1.2 microU/mL), but glucose levels were similar and within normal limits.
      Antiporter activity was measured as sodium-stimulated Li+ efflux by a new
      procedure that uses isosmotic conditions to raise external Na+ to 280 mmol/L. In
      normotensive subjects, Vmax was reached between 50 and 100 mmol/L Na+, whereas in
      most hypertensive subjects, Na+ concentrations higher than 150 mmol/L were
      needed. This different kinetic behavior was because the Na+ concentration for
      half-maximal activation (Km) was twofold higher in hypertensive subjects (58.9 +/
      5.3 mmol/L) than in normotensive subjects (29.8 +/- 2.6 mmol/L, P < .001).
      Hypertensive subjects with fasting insulin levels greater than 10 microU/mL (n =
      12) had a higher Km for Na+ than subjects with insulin levels less than 10
      microU/mL (n = 13) (73.4 +/- 8.7 versus 45.6 +/- 3.9 mmol/L, respectively, P <
      .01) and similar Vmax (0.57 +/- 0.05 versus 0.41 +/- 0.05 mmol.L-1.h-1).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7737739
TI  - Hemodynamic and renal responses to chronic hyperinsulinemia in obese, insulin
      resistant dogs.
AB  - We previously reported that chronic hyperinsulinemia does not cause hypertension
      in normal insulin-sensitive dogs. However, resistance to the metabolic and
      vasodilator effects of insulin may be a prerequisite for hyperinsulinemia to
      elevate blood pressure. The present study tested this hypothesis by comparing the
      control of systemic hemodynamics and renal function during chronic
      hyperinsulinemia in instrumented normal conscious dogs (n = 6) and in dogs made
      obese and insulin resistant by feeding them a high-fat diet for 6 weeks (n = 6).
      After 6 weeks of the high-fat diet, body weight increased from 24.0 +/- 1.2 to
      40.9 +/- 1.2 kg, arterial pressure rose from 83 +/- 5 to 106 +/- 4 mm Hg, and
      cardiac output rose from 2.98 +/- 0.29 to 5.27 +/- 0.54 L/min. Insulin
      sensitivity, assessed by fasting hyperinsulinemia and by the hyperinsulinemic
      euglycemic clamp technique, was markedly reduced in obese dogs. Insulin infusion
      (1.0 mU/kg per minute for 7 days) in obese dogs elevated plasma insulin from 42
      +/- 12 microU/mL to 95 to 219 microU/mL but failed to increase arterial pressure,
      which averaged 106 +/- 4 mm Hg during control and 102 +/- 4 mm Hg during 7 days
      of insulin infusion. Hyperinsulinemia for 7 days in obese dogs elevated heart
      rate from 116 +/- 8 to 135 +/- 7 beats per minute but caused no significant
      changes in cardiac output, in contrast to normal dogs (n = 6), in which marked
      increases in cardiac output (31 +/- 5% after 7 days) and decreases in total
      peripheral resistance occurred during chronic insulin infusion.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7737740
TI  - Inappropriate accommodation in communication to elders: inferences about
      nonverbal correlates.
AB  - According to Communication Accommodation Theory, overaccommodation in
      intergenerational communication with elders is frequently based on stereotyped
      expectations of frailty and dependence. This study examined the role of nonverbal
      behaviors in such overaccommodation. Adult volunteers (N = 120; mean age = 29
      years) read either a patronizing or neutral version of one of three conversations
      between a nursing home resident and a nurse. As in our earlier study, the nurse's
      use of the patronizing conversational style was rated as less respectful, less
      nurturant, and more frustrating for the resident than the neutral style. The main
      analyses indicated that negative nonverbal behaviors were rated as significantly
      more likely to occur with the patronizing style while positive nonverbal
      behaviors were rated as significantly less likely. The negative evaluative impact
      of patronizing style was especially apparent for instrumental task situations
      with high compliance demands. The effects for conversational style were
      essentially replicated for a smaller sample (N = 50) of formal care providers.

PMID- 7737741
TI  - The effects of a confidant and a peer group on the well-being of single elders.
AB  - A study of 100 elderly people was carried out to compare the predictions of well
      being derived from the confidant model with those derived from the Weiss model.
      The confidant model predicts that the most important feature of a person's social
      network for the well-being of that person is whether or not the person has a
      confidant. The Weiss model states that different persons are needed to fulfill
      the different needs of the person and in particular that a confidant is important
      to the need for intimacy and emotional security while a peer group of social
      friends is needed to fulfill sociability and identity needs. The two models were
      evaluated by comparing the relative influence of the confidant variable with the
      peer group variable on subject's well-being. Regression analysis was carried out
      on the well-being measure using as predictor variables the confidant variable,
      peer group variable, age, health, and financial status. The confidant and peer
      group variables were of equal importance to well-being, thus confirming the Weiss
      model.

PMID- 7737742
TI  - Integrity promoting care of demented patients: patterns of interaction during
      morning care.
AB  - Video-recorded morning care sessions (n = 49) of demented nursing home patients
      (n = 5), were analyzed before, as well as after, training of the staff in
      integrity promoting care. A phenomenological-hermeneutic analysis was performed
      based on the Erikson theory of "eight stages of man" and musical notations were
      used for the analysis of courses of events. The analysis revealed five main
      patterns of interaction; positive, negative, intermediate, negative/intermediate
      turned into positive by the patient, and negative/intermediate turned into
      positive by the caregiver. Before the training, negative and intermediate
      patterns dominated (58%), while positive patterns dominated (84%) after the
      training. The positive patterns of interaction were characterized by the
      caregiver communicating with the patient as a competent partner, showing
      humanity, respect and support. The activity was carried out in intimacy. This led
      to the patient displaying more and more ability.

PMID- 7737743
TI  - Mentoring-reminiscence: a conceptual and empirical analysis.
AB  - The quality of reminiscence research is often undermined by a lack of conceptual
      clarity regarding the particular type of reminiscence experience under study. The
      conceptual meaning of reminiscence is structured in part by the context in which
      it is experienced. Accounting for contextual factors is thus an important step
      toward achieving conceptual validity. In the case of interpersonal reminiscence
      the role occupied by the reminiscing subject is an important contextual factor
      which should be accounted for. Interviews were conducted with elders (N = 12) who
      had participated in a three-month, college-based life histories project involving
      mentoring-reminiscence--reminiscing while occupying the role of mentor. Ten
      elders reported that participation had been a positive and enjoyable experience,
      and four of these reported significant improvements in self-image. These outcomes
      are attributed to the fact that mentoring-reminiscence situates elders in a role
      involving status, an intergenerational relationship, and purposeful and
      productive activity.

PMID- 7737744
TI  - Are health care professionals ready for Alzheimer's disease: a comparison of U.S.
      and Hong Kong nurses.
AB  - The Alzheimer's Disease Knowledge Test (ADK) was administered to samples of
      practicing nurses in the United States and Hong Kong. Nurses experienced with
      Alzheimer's Disease patients, having specific training on AD, and reporting
      greater knowledge about AD were, in fact, more knowledgeable. Overall, U.S.
      nurses were significantly more knowledgeable, but exhibited more negative bias
      than Hong Kong nurses. Findings suggest that nurses in Hong Kong, as well as in
      the United States, need more training about Alzheimer's disease.

PMID- 7737746
TI  - 4th Annual meeting of the Thrombosis Study Group. Tokyo, Japan, 17 December 1993.

PMID- 7737745
TI  - Plasma thrombomodulin as an indicator of thromboembolic disease in systemic lupus
      erythematosus.
AB  - We serially measured the plasma thrombomodulin (TM) levels in systemic lupus
      erythematosus (SLE) patients and assessed them clinically. The patients who
      responded to medical treatment experienced a decrease in plasma TM levels.
      Patients who developed exacerbations of SLE, thrombotic thrombocytopenic purpura
      or thrombosis, displayed increased plasma TM levels. There was no significant
      difference between the plasma TM levels of the lupus anticoagulant-positive (LAC
      positive) patients and the LAC-negative patients or between the plasma TM levels
      of the anticardiolipin antibody-positive (aCL-positive) patients and the aCL
      negative patients. While LAC and aCL titers did not always coincide with
      improvement in the patients' clinical course or with aggravation of the disease,
      the TM values correlated well with the patients' clinical condition. Plasma TM
      values may be used to evaluate disease activity and may predict the occurrence of
      thrombosis in SLE.

PMID- 7737747
TI  - Quantitative determination of circulating platelet microparticles by flow
      cytometry.
AB  - Platelet microparticles are vesicles derived from the plasma membrane of
      platelets activated by a variety of agonists. To assess the extent of platelet
      activation, we recently developed a new and simple method of quantitating
      circulating microparticles in plasma by flow cytometry using the murine
      monoclonal antibody against glycoprotein IIb-IIIa (NNKY1-32). Using 2-microns
      fluorescent calibration beads, we succeeded in evaluating the absolute level of
      circulating microparticles. We determined the microparticle concentrations in 10
      patients with arterial occlusive disease and in nine normal healthy donors, to
      determine whether the detection of microparticles would be useful in assessing
      the degree of platelet activation in clinical disorders. Microparticle levels
      were significantly higher in patients not treated with anti-thrombotic drugs than
      in normal healthy donors (P < 0.001), but not significantly higher in patients
      with vascular prostheses who had received anti-thrombotic drugs. These
      observations suggest the usefulness of microparticle quantitation in assessing
      the platelet activation in arterial occlusive diseases.

PMID- 7737748
TI  - Effect of lipoproteins on tissue factor activity and PAI-II antigen in human
      monocytes and macrophages.
AB  - Expression of the tissue factor (TF) and the plasminogen activator inhibitor-II
      were induced in cultured human monocytes-macrophages by incubation with
      lipoproteins. Very low-density lipoprotein (VLDL) augmented the TF and PAI-II
      expression the most, followed by low-density lipoprotein (LDL) and a very weak
      effect by high-density lipoprotein (HDL). In macrophages pre-cultured for 3 days,
      oxidized LDL augmented the expression of TF activity in the macrophages to a
      greater extent than native LDL. These findings indicate that lipoproteins affect
      both monocytes and macrophages, and that they induce a hypercoagulable
      hypofibrinolytic state. Thus hyperlipidemia may be a direct risk factor for
      thrombotic disease.

PMID- 7737749
TI  - Long-term follow-up of coronary narrowing with spasm.
AB  - In order to clarify the fate of coronary narrowing with spasm, repeat angiograms
      of coronary narrowing with and without spasm were compared. The mean interval
      between the first and second angiograms was 3.6 years (range, 1.1-8.5 years).
      Improvement of narrowing was more frequent in the vasospastic group (23%) than in
      the group without spasm (3%, P < 0.005). The cause of this improvement in the
      vasospastic group may have been the resolution of the spasm in the first
      angiogram, but the presence of intravascular thrombus or bleeding or edema of the
      coronary arterial wall may have resolved in the second angiogram.

PMID- 7737750
TI  - Clinicopathological characterization of cardiac free wall rupture in patients
      with acute myocardial infarction: difference between early and late phase
      rupture.
AB  - Differences in morphological characteristics have been described in early phase
      and late phase post-infarction cardiac rupture. In this study, the
      clinicopathological characteristics of early and late phase rupture have been
      clarified by reviewing the clinical records of 1450 consecutive patients with
      acute myocardial infarction (AMI). Rupture of the left ventricular free wall
      (blow-out type) developed in 27 of the 1450 patients, and these patients were
      divided into two groups on the basis of the rupture time: early phase (< 72 h)
      and late phase (> 4 days). Only one patient had a history of prior infarction.
      Early phase rupture was characterized by an abrupt slit-like tear in the
      infarcted myocardium, a preference for anterior infarction sites, no prior
      myocardial infarction, and no difference in incidence in conventional and
      reperfusion therapy, while late phase rupture was characterized by the presence
      of infarct expansion, no preferential infarct site and a very low incidence in
      patients with successful reperfusion. Hence, early and late phase cardiac rupture
      differ in their pathogenesis, and thus the approach to the prevention and
      prediction of early and late phase cardiac rupture should be different.

PMID- 7737751
TI  - Effect of successful angioplasty following thrombolysis on infarct size and left
      ventricular function.
AB  - The role of the angioplasty following thrombolysis in acute myocardial infarction
      has been discussed in several studies, however the effect of successful
      angioplasty on infarct size and left ventricular function has not been properly
      evaluated. Successful reperfusion was achieved in 79 out of 104 patients with
      primary anterior acute myocardial infarction. These patients were classified as
      follows, according to the type of intervention during the acute phase: 50
      patients in which thrombolysis was successful (the thrombolysis group); 12
      patients who underwent successful immediate angioplasty following successful
      thrombolysis (the immediate angioplasty group); and 17 patients in which rescue
      angioplasty was successful (the rescue angioplasty group). The 25 patients whose
      infarct-related vessels were not reperfused after intervention were classified as
      the non-reperfused group. Infarct size, evaluated as defect volume by T1-201
      SPECT, 1 month after the onset, was 840 +/- 154 units (mean +/- S.D.) in the
      immediate angioplasty group and was similar to that in the thrombolysis group
      (948 +/- 88 units), but significantly smaller than in the non-reperfused group
      (1759 +/- 108 units). There were no significant differences in left ventricular
      function in the immediate angioplasty group and the thrombolysis group.
      Successful rescue angioplasty did not have any beneficial effect on left
      ventricular functions or infarct size, when compared with the failed thrombolytic
      group (1105 +/- 169 units vs. 1617 +/- 169 units). End-diastolic volume (52 +/- 3
      ml/m2) in the successful rescue angioplasty group, however, was significantly
      smaller than in the failed thrombolysis group (67 +/- 3 ml/m2).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7737752
TI  - Restenosis after successful emergency coronary angioplasty for acute myocardial
      infarction: comparison with elective angioplasty.
AB  - We investigated the initial and late restenosis rate after successful emergency
      coronary angioplasty in 64 patients with acute myocardial infarction, and
      compared these results with those of 100 patients (110 lesions) who had
      successful angioplasty on an elective basis. The majority of the baseline
      clinical and angiographic variables were similar in the myocardial infarction and
      elective groups. The restenosis rate at 1 month was high in patients undergoing
      emergency angioplasty for acute myocardial infarction (23 vs. 12%). At 3-6
      months, the angiographic restenosis rate was low for the infarction group (26 vs.
      37%). The overall restenosis rate was similar in the infarction and elective
      groups (39 vs. 40%). Lesion regression after coronary angioplasty was more
      frequent in the infarction than in the elective angioplasty group (27 vs. 14%, P
      < 0.05). These findings suggest that considering the high restenosis rate at 1
      month and the lower, but still 20% or more, rate at 3-6 months, a follow-up
      angiography should be performed both prior to discharge and at 3-6 months after
      the procedure, in patients with acute myocardial infarction.

PMID- 7737753
TI  - Perioperative changes in coagulative and fibrinolytic function during surgical
      treatment of abdominal aortic aneurysm and arteriosclerosis obliterans.
AB  - To determine the factors which influence perioperative coagulative and
      fibrinolytic function, we studied 41 patients who underwent surgical repair of
      unruptured abdominal aortic aneurysm (AAA) and 30 patients who underwent arterial
      reconstruction for arteriosclerosis obliterans (ASO). In patients with AAA, the
      levels of fibrin/fibrinogen degradation products (FDP) (11.4 +/- 20.1
      micrograms/ml), thrombin-antithrombin III complex (TAT) (22.0 +/- 21.8
      micrograms/l), plasmin-alpha 2 plasmin inhibitor complex (PIC) (2.6 +/- 2.9
      micrograms/ml) and d-dimer of cross-linked fibrin degradation products (D-D) (8.4
      +/- 10.8 micrograms/ml) were elevated, particularly when the AAAs had a large
      mural thrombus surface area or were accompanied by aneurysm of the iliac or
      femoral artery. In arterial aneurysms, blood coagulability and secondary
      fibrinolytic activity were believed to be enhanced. In patients with ASO, the
      level of TAT (17.2 +/- 24.8 micrograms/l) was so elevated that they were
      considered to show chronic hypercoagulability. Among the ASO patients with aorto
      iliac lesions, those with concomitant graft occlusion or anastomotic aneurysm had
      significantly elevated levels of TAT. Proximal arterial occlusion or accompanying
      aneurysm in the ASO patients was associated with increased levels of PIC and D-D.
      Postoperative fluctuations in conventional hematological variables did not differ
      significantly among the surgical procedures. Conventional markers showed a
      transient decrease due to consumption during surgery, and a subsequent recovery
      or an actual increase within several days after surgery.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7737754
TI  - Study on thrombus formation and the course of healing after sclerotherapy for
      varicose veins of the leg (preliminary report).
AB  - Varicose veins of the leg with saphenous trunk incompetence have been treated
      surgically. However, recently we have switched to sclerotherapy, and the
      preliminary results have been satisfactory. We examined varicosities in the leg
      by color-coded duplex scanning to evaluate venous incompetence and the results of
      sclerotherapy. Our sclerotherapy procedure was performed as follows: the
      varicosed branches were punctured and less than 5 ml of 3% polidocanol was
      injected with the patient's legs raised; an elastic bandage was applied for 3-7
      days. Before sclerotherapy, saphenous incompetence was detected in 31 out of 32
      limbs. One to two weeks after sclerotherapy, 22 limbs with greater saphenous
      trunk incompetence were re-examined. The saphenous trunk was occluded with
      thrombus and saphenous incompetence had diminished in 16 limbs, and there was
      excellent sclerosis of the distal varicosities. The saphenous trunk was not
      sclerosed in six limbs. The varicosity was sclerosed in two out of these six
      limbs. We followed up the healing course of the saphenous vein thrombosis in nine
      limbs for up to 6 months. Six recanalizations of the saphenous veins were
      observed, however, clinically the distal varicosity did not recur in any of these
      limbs. Sclerotherapy appears to be a clinically useful method capable of
      replacing surgery.

PMID- 7737756
TI  - Special issue: Hypnosis and delayed recall, part II.

PMID- 7737755
TI  - Increased heparin-releasable platelet factor 4 and D dimer in patients one month
      after the onset of acute myocardial infarction: persistent activation of
      platelets and the coagulation/fibrinolytic system.
AB  - To evaluate the activity of platelets and the coagulation/fibrinolytic system 1
      month after the onset of acute myocardial infarction, we measured the plasma
      levels of molecular markers, i.e. beta-thromboglobulin, platelet factor 4,
      thrombin-antithrombin III complex and D dimer, in 16 patients with acute
      myocardial infarction and in 11 normal subjects. Blood was drawn through a
      catheter placed in the pulmonary artery before heparin injection. The heparin
      releasable platelet factor 4 was calculated by subtracting the level before the
      injection of 5000 U of heparin, from the level 5 min after injection. The plasma
      beta-thromboglobulin, thrombin-antithrombin III complex and the D dimer levels in
      the acute phase of myocardial infarction were 134.9 +/- 121.2, 11.2 +/- 7.1 and
      164.4 +/- 115.3 ng/ml, respectively. These values were significantly higher than
      those in the normal subjects. The plasma levels of beta-thromboglobulin and
      thrombin-antithrombin III complex, 1 month after the onset (36.6 +/- 16.4 and 4.6
      +/- 2.3 ng/ml, respectively) were not significantly different from those of the
      normal subjects. In contrast, D dimer and heparin-releasable platelet factor 4
      were 216.9 +/- 176.9 and 80.5 +/- 29.3 ng/ml, respectively, and significantly
      higher than in the normal subjects. These findings suggest a latent but
      persistent activation of the platelets and the coagulation/fibrinolytic system 1
      month after the onset of acute myocardial infarction.

PMID- 7737757
TI  - Report on memories of childhood abuse. American Medical Association Council on
      Scientific Affairs.

PMID- 7737758
TI  - Incest memories recalled in hypnosis--a case study: a brief communication.
AB  - Accuracy of repressed memories recovered in hypnosis cannot be reliably
      determined with any greater certainty than non-hypnotically recalled events.
      Therefore, the practice of therapists' accepting hypnotically enhanced memories
      as veridical, absent corroborating evidence, is not advocated. A 52-year-old
      woman with a 27-year history of panic attacks and sleep disorder inadvertently
      recovered incest memories in hypnosis. Photographs and remembered events by other
      family members were thought by the patient to provide general support although
      they did not constitute actual proof of abuse. Implications are discussed.

PMID- 7737759
TI  - Hypnosis, childhood trauma, and dissociative identity disorder: toward an
      integrative theory.
AB  - It is contended that prevailing exogenous trauma theory provides in most cases
      neither a sufficient nor a necessary explanation for the current large number of
      diagnosed cases of dissociative identity disorder (multiple personality disorder)
      and related dissociative syndromes purported to have arisen as a response to
      severe early childhood physical and sexual abuse. Relevant aspects of instinctual
      drive theory, ego psychology, object relations theory, self psychology, social
      psychological theory, sociocultural influences, and experimental hypnosis
      findings are drawn on to demonstrate the importance of adopting a more
      integrative theoretical perspective in the diagnosis and treatment of severe
      dissociative syndromes. Further cooperative experimental and clinical research on
      the etiology, prevalence, and clinical manifestations of the group of
      dissociative disorders is strongly encouraged.

PMID- 7737760
TI  - Some additional light on the childhood sexual abuse-psychopathology axis.
AB  - This exposition is an attempt to unravel the complexities of the relationship
      between childhood sexual abuse and adult psychopathology. Four facets of the
      relationship are examined in some detail: (a) the extent of childhood sexual
      abuse; (b) the probability that sexual abuse in childhood will result in
      psychopathology in the adult; (c) the reliability of early life memories in later
      life; and (d) the role of recovered memory of trauma in the healing process. The
      conclusions of this logico-empirical analysis are that first, government
      statistics tend to underestimate the extent of childhood sexual abuse, whereas
      independent surveys tend to overestimate it. Estimating prevalence is further
      complicated by variations in the definitions of key terms. Possibly the only safe
      conclusion is that true prevalence cannot be reliably determined. Second,
      empirical investigations of childhood sexual abuse conclude that not all victims
      are emotionally injured. A substantial number of these investigations find that a
      majority of victims suffer no extensive harm. Other variables such as family
      dynamics are involved; there may be only a few cases in which emotional harm
      results from sexual abuse as a single factor. Third, memory research suggests
      that memory in general is a dynamic, reconstructive process and that recall of
      childhood events is particularly vulnerable to distortion. Memory cannot
      dependably produce historical truth. Last, there is some clinical evidence that
      abreaction of a traumatic event in adulthood may have a remediative effect.
      Similar evidence for childhood trauma is lacking. The belief in the healing
      effect of recalling and reliving a childhood trauma depends on the therapist's
      orientation.

PMID- 7737761
TI  - On the belief that one body may be host to two or more personalities.
AB  - The belief in the validity of the multiple personality concept is discussed in
      this article. Two scaffolding constructions are analyzed: dissociation and
      repression. As generally employed, these constructions grant no agency to the
      multiple personality patient. The claim is made that the conduct of interest
      arises in discourse, usually with the therapist as the discourse partner. In
      reviewing the history of multiple personality and the writings of current
      advocates, it becomes clear that contemporary users of the multiple personality
      disorder diagnosis participate in a subculture with its own set of myths, one of
      which is the autonomous actions of mental faculties. Of special significance is
      the readiness to transfigure imaginings into rememberings of child abuse, leading
      ultimately to the manufacture of persons. The implications for both therapy and
      theory of regarding the patient as agent in place of the belief that the
      contranormative conduct is under the control of mentalistic faculties are
      discussed.

PMID- 7737762
TI  - Fantasy proneness, reported childhood abuse, and the relevance of reported abuse
      onset.
AB  - This study investigated the relationship between fantasy proneness and the age at
      which reported childhood sexual abuse occurs. Seventeen adult females who
      reported having been sexually abused before the age of 7 years, 20 females who
      reported having been abused after the age of 7 years, and 20 females who reported
      having never been abused were administered two measures of imaginative
      involvement (Tellegen Absorption Scale [TAS] and Inventory of Childhood Memories
      and Imaginings [ICMI]). Participants who were reportedly abused early in
      childhood obtained higher scores on the TAS and ICMI than participants who were
      reportedly abused later in childhood, who in turn obtained higher scores than the
      control participants. Findings are discussed in terms of factors that mediate
      fantasy proneness and reports of childhood abuse.

PMID- 7737763
TI  - The illusion of familiarity: an alternative to the report-criterion account of
      hypnotic recall.
AB  - Hypnosis increases the likelihood that participants will report incorrect
      material at higher levels of confidence. One interpretation of such data is that
      hypnosis induces individuals to lower the criterion they use to make memory
      reports. A lowered report criterion could account for the increase in items that
      participants are willing to report as memories but not for the increase in
      confidence that typically accompanies hypnotic retrieval. Although some
      participants may indeed lower their report criterion, this alone should not
      result in the highly confident confabulation so often observed. An alternative
      perspective is that for some participants, hypnosis alters the experience of
      retrieval such that items generated during retrieval attempts are more likely to
      have the qualities (e.g., perceptual fluency, vividness) usually associated with
      remembering. This illusion of familiarity would account for the higher levels of
      confidence that are so frequently observed in hypnotic recall, and adopting this
      perspective should lead to even greater caution in the use of hypnosis as an aid
      to retrieval.

PMID- 7737764
TI  - The admissibility of hypnotic evidence in U.S. Courts.
AB  - For the past two decades, the American judiciary has confronted the admissibility
      of hypnotic evidence in criminal prosecutions. These courts have uniformly
      rejected the admissibility of out-of-court statements made while an individual is
      in hypnosis. In contrast, the courts divided sharply over the admissibility of
      hypnotically refreshed testimony. Some courts adopted a per se rule of exclusion;
      these courts, however, also carved out exceptions for testimony based on
      prehypnotic memory and testimony of the accused. Courts admitting hypnotically
      refreshed testimony adopted three different positions: (a) a "credibility"
      approach, which left the reliability issue to the jury; (b) a "discretionary
      admission" approach, which left the reliability issue to the trial judge; and (c)
      a "procedural safeguards" approach. In addition, constitutional concerns played
      an influential role in some of these cases. This diversity in the case law often
      resulted from a judicial failure to understand the scientific research on
      hypnosis. Courts have also considered the use of hypnosis as a basis for expert
      testimony about an accused's mental state. Unless the advantages of hypnotically
      refreshed testimony are significant, why add more problems?

PMID- 7737765
TI  - Trivial or terrible? The psychosocial impact of psoriasis.
AB  - BACKGROUND: Psoriasis remains a chronic disease with lesions that are often
      extensive and disfiguring. While the potential for psychosocial morbidity and
      impairment are recognized, the literature remains equivocal with regard to the
      prevalence and degree of this impairment. METHODS: The present study utilized a
      new questionnaire designed to assess the type and degree of psychosocial
      impairment present among psoriasis patients. The questionnaire was designed to
      assess major areas of psychosocial functioning and was completed by 64 patients
      undergoing outpatient treatment. RESULTS: Approximately half the patients were
      found to have moderate to extreme levels of anxiety, depression, and anger.
      Patients reported experiencing these negative emotional sequelae both during
      their disease flares and during periods of remission. Patients were also found to
      have moderate to extreme levels of pruritus associated with their flares.
      Psychologic morbidity was positively associated with length of disease flare.
      Significant levels of social embarrassment, life disruption, and social
      withdrawal were found as well. CONCLUSIONS: Psoriasis does appear to cause
      significant psychosocial morbidity. Greater awareness by physicians and more
      comprehensive treatment addressing these psychosocial components may avert, or at
      least minimize, some of these negative sequelae.

PMID- 7737766
TI  - Generalized non-Langerhans cell histiocytosis: four cases illustrate a spectrum
      of disease.
AB  - BACKGROUND: The proliferation of non-Langerhans cell histiocytes is a poorly
      understood process of unknown cause. Variation in the clinical features and/or
      histopathology of histiocytic proliferation has led to subclassification of the
      general category of non-Langerhans cell histiocytes. Although the current
      classification may provide some useful generalizations in regard to the
      anticipated clinical course, wide variability in presentation and outcome make
      this classification less than optimal when dealing with individual patients. The
      objectives of the study were to present four cases of generalized non-Langerhans
      cell histiocytosis. MATERIALS AND METHODS: Medical records and slides of four
      patients diagnosed with non-Langerhans cell histiocytosis at the Cleveland Clinic
      are reviewed. RESULTS: The patients exhibit features of more than one subtype of
      non-Langerhans cell histiocytosis. CONCLUSION: The overlap among the clinical and
      histologic features of the generalized cutaneous non-Langerhans cell histiocytic
      disorders suggests that they represent one disease entity with a wide spectrum of
      presentations rather than many distinct disorders.

PMID- 7737767
TI  - Transient acantholytic dermatosis in a postoperative febrile patient.

PMID- 7737768
TI  - Visceral leishmaniasis with cutaneous and rectal dissemination due to Leishmania
      braziliensis in acquired immunodeficiency syndrome (AIDS).

PMID- 7737769
TI  - Bilateral pigmented Bowen's disease of the lower lip.

PMID- 7737770
TI  - Erythematous exanthem associated with primary infection by human parvovirus B19.

PMID- 7737771
TI  - Failure of ketoconazole treatment in cutaneous leishmaniasis.

PMID- 7737772
TI  - Tinea pedis (mocassin-type) treated with itraconazole.

PMID- 7737773
TI  - Double-blind comparison of miconazole/corticosteroid combination versus
      miconazole in inflammatory dermatomycoses.

PMID- 7737774
TI  - Treatment of recurrent cutaneous Leishmaniasis.
AB  - BACKGROUND: Cutaneous leishmaniasis is endemic in Iran. One of the clinical
      pictures of this disease is leishmaniasis recidivans (LR). Most of the drugs used
      for cutaneous leishmaniasis are ineffective in LR. METHODS AND PATIENTS: Twenty
      five patients (13 women and 12 men), who had LR and whose disease had been proved
      by previous direct smears, were accepted for the study. The duration of disease
      in all patients was more than 2 years and they had previously been treated for
      their cutaneous leishmaniasis by different methods. All patients were treated
      with a combination of allopurinol (AL) (20 mg/kg/day for 30 days) and meglumine
      antimoniate (MA) (70 mg/kg/day for 15 days). Laboratory tests including
      hemograms, liver function, and kidney function tests, were done both at baseline
      and at the end of therapy. RESULTS: Twenty-four out of 25 patients (96%)
      responded well to treatment and after 1 year follow-up no relapse had occurred.
      The drugs were well tolerated by the patients producing no side effects nor any
      significant changes in laboratory values. CONCLUSIONS: A combination of AL and
      antimoniate is an effective method for the treatment of LR and for patients with
      cutaneous leishmaniasis who are resistant to the usual treatments.

PMID- 7737775
TI  - Treatment of psoriasis at a Dead Sea dermatology clinic.
AB  - BACKGROUND: The Dead Sea, with its unique optical, chemical, and atmospheric
      properties, provides an effective alternative treatment for psoriasis. METHODS:
      The records of 1448 consecutive psoriasis patients treated at a Dead Sea
      psoriasis clinic were retrospectively evaluated concerning their treatment
      response and demographic characteristics. RESULTS: Clearing of 80-100% was
      observed in 88% of the patients treated, including almost 58%, who had complete
      clearing. The demographic data studied that included gender, previous treatment
      at the Dead Sea, prior history of hospitalization for psoriasis, prior PUVA
      treatment, or a history of arthritis did not reveal any significant
      relationships, although overseas patients responded considerably better than
      Israelis. CONCLUSIONS: The overall response in a large cohort of psoriasis
      patients treated at the Dead Sea was excellent. Further prospective studies and
      basic investigations are essential to understand the mechanism(s) involved and
      the relationships between other demographic data and the treatment response.

PMID- 7737776
TI  - Open randomized comparison of itraconazole versus terbinafine in onychomycosis.
AB  - BACKGROUND: Onychomycoses are among the most frequent nail diseases. The
      principal agents are dermatophytes. Itraconazole and terbinafine are two
      effective and systemic antimycotics. Previous trials have shown, that treatment
      schedules with effective concentrations for 3 months cause drug deposits in nail
      plates that persist 6 months after the end of the treatment. METHODS: A
      comparative, open, prospective study was carried out with random assignment of
      patients. The first group included 27 patients under treatment with 200 mg of
      itraconazole once daily for 3 months. The second group included 26 patients
      treated with 250 mg of terbinafine for 3 months. Both series of patients were
      followed for 6 additional months. RESULTS: Both groups were similar in age, sex,
      and history of onychomycosis. Trichophyton rubrum was the main isolated agent in
      all patients. The percentage of diseased nails was similar in both groups
      affecting predominantly the first toenail. Treatment was highly effective and
      differences between groups were not significant. The rate of adverse events was
      21% in the itraconazole group and 47% in the terbinafine group. CONCLUSIONS:
      Itraconazole and terbinafine are two drugs of choice in dermatophytic
      onychomycosis.

PMID- 7737777
TI  - Anetodermic cutaneous changes overlying pilomatricoma.

PMID- 7737778
TI  - Treatment of subcutaneous phycomycosis with ketoconazole.

PMID- 7737779
TI  - Lupus vulgaris: morphology.

PMID- 7737780
TI  - Erosive pustular dermatosis of the scalp in association with rheumatoid
      arthritis.

PMID- 7737781
TI  - Azelaic acid: pharmacokinetic and pharmacodynamic properties and its therapeutic
      role in hyperpigmentary disorders and acne.

PMID- 7737782
TI  - Post-kala-azar dermal leishmaniasis.

PMID- 7737783
TI  - Fish-odor syndrome: an olfactory diagnosis.

PMID- 7737784
TI  - Pharmaceutical development process.

PMID- 7737785
TI  - Classification and diagnosis of erythromelalgia and erythermalgia.

PMID- 7737786
TI  - The consulting psychiatrist and the polydipsia-hyponatremia syndrome in
      schizophrenia.
AB  - OBJECTIVE: The authors seek to extend understanding and treatment of hospitalized
      schizophrenics presenting with complications of polydipsia and dilutional
      hyponatremia. Attending physicians may ask the consultation/liaison psychiatrist
      to see schizophrenics with hyponatremically-induced delirium or other psychiatric
      syndromes. The referring physician may or may not have identified polydipsia and
      dilutional hyponatremia and their complications. This article will help the
      consultation/liaison psychiatrist recognize early evidence of water imbalance,
      describe evaluation, and provide somatic and behavioral treatment approaches to
      this life-threatening syndrome. METHOD: Over the past ten years, the authors have
      treated more than 100 patients with the polydipsia-hyponatremia syndrome. The
      authors discuss their and others' experience with drugs that help and hinder
      patients suffering from dilutional hyponatremia. They review current key articles
      from the polydipsia-hyponatremia syndrome literature including articles
      identified via Medline search 1985-94. RESULTS: Schizophrenics with the
      polydipsia-hyponatremia syndrome most commonly present with polydipsia, polyuria,
      urinary incontinence, cognitive, affective, and behavioral changes, seizures, or
      coma. Quantitating polydipsia, hyponatremia, and diurnal changes in body weight
      facilitate therapeutic interventions. Treatment include patient and caregiver
      education, drug therapies to better treat psychosis and better treat osmotic
      dysregulation, behavioral interventions to interdict polydipsia, and diurnal
      weight monitoring. CONCLUSIONS: Once recognized, acute, subacute, and chronic
      complications of the polydipsia-hyponatremia syndrome are readily treatable.
      Besides treating the patient, consultation/liaison psychiatrists can teach their
      medical colleagues about this syndrome. In so doing, they will enhance the
      quality of their patients' lives and help the internist and surgeon feel more
      comfortable when working with schizophrenics.

PMID- 7737787
TI  - The co-occurrence of mania with medical and other psychiatric disorders.
AB  - OBJECTIVE: The co-occurrence of mania with other medical and psychiatric
      disorders has been little studied. The authors reviewed the literature in order
      to clarify the current state of knowledge of this subject and to identify
      possible areas of future research. METHODS: Published articles which specifically
      addressed associations of mania with medical disorders and other psychiatric
      syndromes were identified using the Paperchase medical literature search system
      and by cross-referencing from other published work. The articles were then
      organized into three categories: 1) medical disorders associated with secondary
      mania; 2) medical comorbidity in bipolar disorder; and 3) psychiatric comorbidity
      in bipolar disorder. RESULTS: The review of medical illness and secondary mania
      supports the hypothesis that injuries involving right-side and mid-line brain
      structures are associated with so-called secondary mania. Additionally, an
      association between bipolar disorder and migraine is identified. Several
      psychiatric disorders appear to occur with mania at rates higher than expected
      including obsessive-compulsive disorder, bulimia nervosa, panic disorder, impulse
      control disorders, and substance abuse. CONCLUSIONS: The authors discuss the
      potential implications of these findings and suggest research approaches to
      further examine the relationships between mania and other medical and psychiatric
      syndromes.

PMID- 7737788
TI  - Catatonia on the consultation-liaison service: a replication study.
AB  - OBJECTIVE: The aim of this study is to identify the frequency, presentation,
      identification, treatment recommendations and outcome of patients with catatonia
      in the general hospital setting. METHOD: All patients seen on a consultation
      liaison (C-L) service over a six-month period were screened prospectively for
      catatonic disorders. Research and DSM-IV criteria for catatonic disorder were
      applied. Treatment and outcome were naturalistic. RESULTS: Five (1.6%) of 297
      patients met restrictive criteria for catatonic disorder. Data were extracted
      from medical charts. Case reports are presented to reflect the diagnosis and
      treatment. Extensive medical treatment was required in most cases and most had an
      unfavorable outcome. CONCLUSION: Catatonia is infrequent but underrecognized in
      medical-surgical settings. The C-L clinician should screen for catatonic signs in
      order to diagnose and treat patients with the catatonic disorders.

PMID- 7737789
TI  - Psychiatric consultations in medical outpatients with abdominal pain: patient and
      physician effects.
AB  - OBJECTIVE: The purpose of the study was to assess the effect of a psychiatric
      consultation intervention in terms of changes in 1) the patients' psychological
      symptoms, and 2) satisfaction of general practitioners (GPs) concerning their
      cooperation with the internists. METHOD: In a randomized controlled design, the
      effect of a psychiatric consultation intervention in medical outpatients with
      abdominal pain (n = 106) has been assessed. The goal of the intervention was 1) a
      holistic approach toward the patients' symptoms, and 2) the improvement of the
      cooperation between primary and secondary medical health services. The
      intervention was designed at the health care provider level; the psychiatrist did
      not see or examine the patient. The 106 patients were subdivided in an index
      group (N = 49) and a control group (N = 57). The major outcome measures were the
      psychological status of the patient and degree of satisfaction of the GPs about
      the cooperation with the medical specialists. RESULTS: At six months follow-up,
      there was a significantly greater decline in depressive symptoms assessed by SCL
      90 in the patient index group compared with the control group. The GPs of the
      index group were significantly more satisfied with the cooperation and
      communication with the internists compared with the control group. CONCLUSIONS:
      An experimental psychiatric consultation intervention did effect the patients'
      well-being to a certain degree, and especially the GPs were affected in terms of
      satisfaction. The relevance of improving the communication between health care
      providers in the management of somatizing patients is discussed.

PMID- 7737790
TI  - Depression following myocardial infarction: a one year longitudinal study.
AB  - OBJECTIVE: The purpose of this study was to examine the course and clinical
      correlates of depression during the first year after myocardial infarction.
      METHOD: A group of seventy patients hospitalized for the treatment of myocardial
      infarction (MI) were assessed for the presence of mood disorders during their
      hospital admission and at three, six, nine, and twelve months follow-up. Patients
      were evaluated and diagnosed using the Present State Examination and DSM-III
      criteria. Impairment in activities of daily living was measured by the Johns
      Hopkins Functioning Inventory and impairment in social functioning was measured
      by the Social Functioning Examination. RESULTS: A total of twenty-four patients
      met DSM-III criteria for major depression at some time during the study (18 in
      the acute stage, 6 during follow-up). There were two patients with minor
      depression (dysthymia) at intake and six developed minor depression during the
      follow-up period. The median duration of major depression was 4.5 months.
      Patients with depression at intake had greater impairment in activities of daily
      living than non-depressed patients. Depressions lasting more than six months were
      more likely to be anxious depressions than those lasting less than six months.
      After the acute MI period, there was a consistent relationship between the
      existence of depression and impaired social functioning. CONCLUSIONS: This is a
      pilot study and needs further replication due to the low rate of follow-up
      participation. However, these data suggest that there may be two types of
      depression following MI: an acute depression associated with greater functional
      impairment, and a prolonged depression that may be associated with inadequate
      social support.

PMID- 7737791
TI  - The use of an advance directive in consultation-liaison psychiatry: a case
      report.
AB  - OBJECTIVE: The following case report illustrates the use of a psychiatric advance
      directive in a surgical setting. METHOD: The case of a woman with breast cancer
      and debilitating pre-operative anxiety is presented. Her anxiety was so severe
      that it resulted in repeated refusal to have necessary surgery. An advance
      directive facilitated proceeding with surgery despite her objections in the
      immediate pre-operative period. CONCLUSION: Consultation-Liaison psychiatrists
      should consider the use of an advance directive when preoperative anxiety
      interferes with decision-making capacity.

PMID- 7737792
TI  - Biology of hypothalamic neurons and pituitary cells.
AB  - Results obtained by examining hypothalamic neurons producing precursors to
      neurohormones, and pituitary cells synthesizing peptide and glycoprotein families
      of hormones, and recent advances in comparative endocrinology, have been
      summarized and considered from the following viewpoints: species specificity in
      the organization and communication of the hypothalamic neurons with different
      brain areas lying inside the BBB and with CVOs; sensitivity of hypothalamic
      neurons and pituitary cells to the environmental stimuli; gonadal steroids as
      modulators of gene expression needed for neuronal differentiation and
      synaptogenesis; dose(s)-dependent pituitary cell proliferation and
      differentiation; an inverse relationship between PRL and GH synthesis and release
      and also between degree of hyperplasia and hypertrophy of PRL cells and
      retardation of GTH cell differentiation; and responsiveness of neurons producing
      CRH, and of neurons and pituitary cells synthesizing POMC hormones, to stress and
      glucocorticosteroids. These data show that growth of the animals may be
      stimulated, retarded, or inhibited; reproductive properties and behavior may be
      under hormonal control; and character of responsiveness in reaction to stress,
      and ability for adaptation and other related functions, may be controlled.

PMID- 7737793
TI  - Nuclear remodeling in response to steroid hormone action.
AB  - Steroid and similar hormones comprise the broadest class of gene regulatory
      agents known, spanning vertebrates through the lower animals, and even fungi. Not
      unexpectedly, therefore, steroid receptors belong to an evolutionarily highly
      conserved family of proteins. After complexing with their cognate ligands,
      receptors interact with hormone response elements on target genes and modulate
      transcription. These actions are multifaceted and only partly understood, and
      include large-scale changes in the structure and molecular composition of the
      affected cell nuclei. This chapter examines steroid hormone action and the
      resultant nuclear remodeling from the following perspectives: (1) Where are the
      receptors located? (2) Which nuclear domains are most affected? (3) Are there
      extended or permanent nuclear changes? (4) What is the role of coiled bodies and
      similar structures in this regard? To address these and related questions,
      information is drawn from several sources, including vertebrates, insects, and
      malignant tissues. Entirely new data are presented as well as a review of the
      literature.

PMID- 7737794
TI  - Effects of axotomy, deafferentation, and reinnervation on sympathetic ganglionic
      synapses: a comparative study.
AB  - The main physiological and morphological features of the synapses in the superior
      cervical ganglia of mammals and the last two abdominal ganglia of the frog
      sympathetic chain are summarized. The effects of axotomy on structure and
      function of ganglionic synapses are then reviewed, as well as various changes in
      neuronal metabolism in mammals and in the frog, in which the parallel between
      electrophysiological and morphological data leads to the conclusion that a
      certain amount of synaptic transmission occurs at "simple contacts." The effects
      of deafferentation on synaptic transmission and ultrastructure in the mammalian
      ganglia are reviewed: most synapses disappear, but a number of postsynaptic
      thickenings remain unchanged. Moreover, intrinsic synapses persist after total
      deafferentation and their number is strongly increased if axotomy is added to
      deafferentation. In the frog ganglia, the physiological and morphological
      evolution of synaptic areas is comparable to that of mammals, but no intrinsic
      synapses are observed. The reinnervation of deafferented sympathetic ganglia by
      foreign nerves, motor or sensory, is reported in mammals, with different degrees
      of efficiency. In the frog, the reinnervation of sympathetic ganglia with somatic
      motor nerve fibers is obtained in only 20% of the operated animals. The possible
      reasons for the high specificity of ganglionic connections in the frog are
      discussed.

PMID- 7737795
TI  - Chondrocyte differentiation.
AB  - Data obtained while investigating growth plate chondrocyte differentiation during
      endochondral bone formation both in vivo and in vitro indicate that initial
      chondrogenesis depends on positional signaling mediated by selected homeobox
      containing genes and soluble mediators. Continuation of the process strongly
      relies on interactions of the differentiating cells with the microenvironment,
      that is, other cells and extracellular matrix. Production of and response to
      different hormones and growth factors are observed at all times and autocrine and
      paracrine cell stimulations are key elements of the process. Particularly
      relevant is the role of the TGF-beta superfamily, and more specifically of the
      BMP subfamily. Other factors include retinoids, FGFs, GH, and IGFs, and perhaps
      transferrin. The influence of local microenvironment might also offer an
      acceptable settlement to the debate about whether hypertrophic chondrocytes
      convert to bone cells and live, or remain chondrocytes and die. We suggest that
      the ultimate fate of hypertrophic chondrocytes may be different at different
      microanatomical sites.

PMID- 7737796
TI  - [Diagnosis of yersinioses and infections with enterohemorrhagic Escherichia
      coli].

PMID- 7737797
TI  - [Diagnosis of legionella infection].

PMID- 7737798
TI  - [Diagnosis of Borrelia burgdorferi infection].

PMID- 7737799
TI  - [Diagnosis of tuberculosis and mycobacterioses].

PMID- 7737800
TI  - [Diagnosis of candida mycoses].

PMID- 7737801
TI  - [Diagnosis of herpesviruses].

PMID- 7737802
TI  - [New developments in diagnosis of viral hepatitis].

PMID- 7737803
TI  - [Etiological assessment of lymphadenopathy].

PMID- 7737804
TI  - [Diagnosis of pulmonary infections].

PMID- 7737805
TI  - [Diagnosis of gastrointestinal infections].

PMID- 7737806
TI  - [Laboratory diagnosis of infections of the central nervous system].

PMID- 7737807
TI  - [Fever in immunosuppressed patients].

PMID- 7737809
TI  - [In the age of ACE inhibitors are there still indications for spironolactone in
      heart failure?].

PMID- 7737808
TI  - [Sotalol].

PMID- 7737810
TI  - [Arterial vascular status].

PMID- 7737811
TI  - [Modern diagnostic procedures in medical microbiology].

PMID- 7737812
TI  - [Primary glomerulonephritis. Classification and clinicopathologic correlates].

PMID- 7737813
TI  - [Glomerulonephritis as a secondary disease. Clinical significance].

PMID- 7737814
TI  - [Therapy of glomerulonephritis].

PMID- 7737815
TI  - [Goodpasture syndrome. Progress in immunopathogenesis, diagnosis and therapy].

PMID- 7737816
TI  - [Lupus nephritis].

PMID- 7737817
TI  - [Glomerulonephritis within the scope of primary systemic vasculitis].

PMID- 7737818
TI  - [Hereditary diseases of the kidney].

PMID- 7737819
TI  - [Problems in long-term follow-up after kidney transplantation].

PMID- 7737820
TI  - [Autoantibodies in nephrology].

PMID- 7737821
TI  - [Antinuclear autoantibodies].

PMID- 7737822
TI  - [Anti-neutrophilic cytoplasmic antibodies (ANCA)].

PMID- 7737823
TI  - [Aneurysm of the hepatic artery as the cause of acute abdomen and liver infarct
      caused by vascular compression].

PMID- 7737824
TI  - [Adenosine].

PMID- 7737825
TI  - [Is it correct that in type II diabetes, treatment with metformin should be
      discontinued starting at age 65?].

PMID- 7737826
TI  - [Significance of thyroid antibodies for diagnosis and follow-up of thyroid
      diseases].

PMID- 7737827
TI  - Pitfalls of integration.

PMID- 7737828
TI  - Antibiotic resistance: an emergency we can't ignore.

PMID- 7737829
TI  - What a difference a generation makes.

PMID- 7737830
TI  - Inflict kindness.

PMID- 7737831
TI  - The management of chronic asthma in childhood.

PMID- 7737832
TI  - The indications and uses of inhaled steroids in asthma.

PMID- 7737833
TI  - Control of meningococcal disease: the responsibility of all.

PMID- 7737834
TI  - Lung-function and glaucoma treatment--a cause for concern?

PMID- 7737835
TI  - Psychoneuroimmunology and suicidal behaviour.

PMID- 7737836
TI  - Nasopharyngeal carcinoma--the Irish experience.
AB  - Ten new cases of nasopharyngeal carcinoma were diagnosed at our unit during a
      recent twelve month period. An evaluation of these cases is presented. This
      stimulated an examination of the national data for the years 1981-1990 and it was
      discovered that 69 cases were diagnosed in that period. A chart review was
      performed of the patients with nasopharyngeal carcinoma that were treated at St.
      Lukes Hospital 10 years previously and compared to the 10 recently diagnosed
      patients. This data highlights: the young age at which this tumour can occur;
      that there has been no improvement in the early detection of these neoplasms and
      the importance of an ENT assessment for patients presenting with cervical
      lymphadenopathy, persisting middle ear effusion or atypical headaches.

PMID- 7737837
TI  - The hospital in-patient enquiry scheme: a study of data accuracy and capture.
AB  - In order to measure the coverage and accuracy of the Hospital In-patient Enquiry
      Scheme data in a large acute hospital in Dublin, 793 patient charts were selected
      randomly from all the discharges in 1990. The capture rate was 56%. Whether a
      diagnosis was captured for the Hospital In-patient Enquiry Scheme depended partly
      upon geographical factors within the hospital and partly upon the nature of the
      diagnosis. "Non-capture" was not random and was particularly likely to occur
      where the case was complex, e.g. oncology, HIV infection. The coding accuracy of
      primary diagnoses was 59% and the completeness of recording of secondary
      diagnoses was 56%. Both were significantly associated with the presence in the
      hospital chart of discharge summaries and with the clarity and source of written
      diagnoses. The factors that affected accuracy were not the same as those
      affecting the capture rate.

PMID- 7737838
TI  - The visual outcome of vitrectomy for advanced diabetic retinopathy.
AB  - The indications for vitrectomy in the management of proliferative diabetic
      retinopathy are increasing. This is due to the improving results associated with
      earlier surgery, improving instrumentation and refinements in technique. The
      current indications for surgery include chronic or recurrent vitreous haemorrhage
      (of at least one months duration), progressive extramacular tractional retinal
      detachment, tractional macular detachment and elevated proliferative diabetic
      retinopathy. This paper reviews a series of 30 vitrectomies performed for severe
      complications of proliferative diabetic retinopathy. Most favourable visual
      outcome was associated with surgery for chronic or recurrent vitreous haemorrhage
      (in the absence of rubeosis iridis) and progressive extramacular tractional
      retinal detachment. Poor visual prognostic factors were, pre-operative rubeosis
      iridis and tractional retinal detachments involving the macula.

PMID- 7737839
TI  - Employing a practice nurse: what sort of GP?
AB  - The general practitioners employing all 102 nurses known to be practising as
      practice nurses in the Republic of Ireland were sent a questionnaire for
      completion anonymously. A response rate of 51% was obtained. Practices employing
      practice nurses were found to be mostly single handed (28/52) in a town/rural
      setting (39/52) and participating in the General Medical Services (GMS) Scheme
      (49/51)*. A substantial minority of practices (16/51)* derived more than 75% of
      their income from the GMS. Eighty five percent of practices felt that their
      practice "gained or would gain financially" through the employment of a practice
      nurse. (* = one non-respondent)

PMID- 7737840
TI  - Sunburn presenting to the accident & emergency department of two north Dublin
      hospitals.
AB  - A retrospective study was carried out in two North Dublin hospitals to determine
      how many patients attended the Accident & Emergency Departments of these
      hospitals with sunburn. 30 patients presented to Beaumont Hospital over a nine
      month period from January to September 1992, 28 of whom attended during the four
      months from 1st May 1992 to 31st August 1992. During the same four month period,
      27 children attended the Accident & Emergency Department of Temple Street
      Hospital for treatment of sunburn. This was a marked increase from the previous
      year, when only six children presented to Temple Street Hospital with sunburn.

PMID- 7737841
TI  - Emergency bail-out stenting for major coronary dissection complicating rotational
      atherectomy.
AB  - The problems of restenosis and abrupt occlusion following percutaneous
      transluminal coronary angioplasty (PTCA) remain a challenge. Restenosis occurs in
      30-50% of lesions treated and substantially erodes the potential advantage of
      percutaneous treatment of obstructive coronary disease over alternative
      revascularisation strategies. Abrupt closure occurs in 5-7% of cases with
      significant associated morbidity and mortality. Up to 35% of patients require
      emergency bypass surgery for treatment of abrupt closure and more than half
      sustain a perioperative myocardial infarction. By debulking atherosclerotic
      lesions, atherectomy offers the potential to reduce restenosis. Coronary
      stenting, by acting as a scaffolding can sometimes solve the problem of abrupt
      closure due to intimal dissection. We report the use of emergency placement of
      multiple coronary stents for obstructive coronary dissection complicating
      rotational atherectomy.

PMID- 7737842
TI  - Congenital diaphragmatic hernia.

PMID- 7737843
TI  - Management of the brittle unstable asthmatic.

PMID- 7737844
TI  - Maintenance therapy of asthma.

PMID- 7737845
TI  - Bronchodilators.

PMID- 7737846
TI  - Medical treatment rights of older persons and persons with disabilities: 1993-94
      developments.

PMID- 7737847
TI  - "Slapping up spastics": the persistence of social attitudes toward people with
      disabilities.

PMID- 7737848
TI  - Assisted suicide and older people--a deadly combination: ethical problems in
      permitting assisted suicide.

PMID- 7737849
TI  - The role of the courts in terminating life-sustaining medical treatment.

PMID- 7737850
TI  - The role of courts in terminating nutrition and hydration for incompetent
      patients.

PMID- 7737851
TI  - Laurie v. Senecal.

PMID- 7737852
TI  - Prevalence of systemic lupus erythematosus in Hawaii: is there a difference
      between ethnic groups?
AB  - This population-based study in Hawaii collected cases of systemic lupus
      erythematosus from medical facilities and a patient support group. A total of 454
      cases was found and the prevalence was estimated at 41.8 per 100,000 population
      for 1989. The prevalence odds ratio for all non-Caucasians compared to Caucasians
      was 1.2 (0.9-1.5), for Japanese 1.3 (1.0-1.7), for Filipinos 1.5 (1.1-2.0), for
      Chinese 2.4 (1.7-3.4), and for Hawaiians 0.8 (0.6-1.1). Mortality rates were 3
      times higher for non-Caucasians than for Caucasians in 1985 to 1989. Despite the
      observed differences, it remains unclear whether individuals with Asian or
      Pacific Islander ancestry are at higher risk for systemic lupus erythematosus.
      The variation in prevalence rates may be a result of differences in access to
      medical care and in survival.

PMID- 7737853
TI  - Adequacy of a pre-participation examination form: a study of Hawaii physicians.
AB  - Many states currently require a medical screening prior to participation in
      organized sports. The purpose of this study was to examine the adequacy of the
      existing pre-participation examination form in Hawaii. One hundred forty-eight
      physicians who perform school health/pre-participation physical examinations were
      surveyed. The results indirectly suggest that these physicians agreed that the
      form should be modified and improved (p, .001).

PMID- 7737854
TI  - Characteristics of long-term mentally ill patients: policy implications.
AB  - This study examined the records of all psychiatric patients who were hospitalized
      over one year in a public sector institution. The 88 patients primarily were men,
      hospitalized under a penal code, Hawaiian or other ethnic minority, and
      unmarried. Over 74% were hospitalized under a penal code. The State is moving
      toward a capitated managed care environment for the seriously and persistently
      mentally ill. With the majority of the patients who are hospitalized under a
      penal code, changes in the public policy concerning their care is needed. If no
      changes are made, all of the existing hospital beds potentially could be filled
      with forensic patients.

PMID- 7737855
TI  - Epinephrine for anaphylaxis.

PMID- 7737856
TI  - Wonder what Hippocrates would say?

PMID- 7737857
TI  - The role of genetics in (continuing) medical education in Hawaii.

PMID- 7737858
TI  - Pre-participation examination: a new form for Hawaii.
AB  - A recent study examining the adequacy of the existing pre-participation physical
      examination (PPE) form in the State of Hawaii suggested that the form be modified
      and expanded. The standards for a comprehensive PPE indicate that the screening
      should include an extensive medical history, assessment of height, weight, blood
      pressure, pulses, vision, cardiopulmonary (heart, and lungs), maturation, skin,
      abdominal, genitalia, and musculoskeletal function. Pursuant to the
      recommendation of this recent study and the accepted standards of the American
      Academy of Family Physicians, American Academy of Pediatrics, American Medical
      Society for Sports Medicine, American Orthopedic Society for Sports Medicine, and
      the American Osteopathic Academy of Sports Medicine, the PPE form utilized by the
      Hawaii High School Athletic Association has been drastically modified. The new
      form includes an expanded medical history, a maturational assessment (Tanner
      Stage), a complete musculoskeletal examination, and a participation clearance and
      recommendation.

PMID- 7737859
TI  - Trends in workers compensation costs in a hotel-operating company over a six-year
      period.
AB  - A large Honolulu-based hotel-operating company reviewed its workers compensation
      costs over the last 6 years. Data retrieved from the company's computerized data
      base is used to describe trends in injury incidence rate, average cost per claim,
      average medical cost per claim, and medical expenses as a percentage of total
      costs. Factors that might have influenced these parameters include company
      reorganization, employee training and safety programs, changes in the economy,
      company morale, aggressive case management, and the quality of the adjusting
      services hired. Cause-and-effect relationships, although suggested, cannot be
      proven. The data is presented, in this year of imminent workers compensation
      legislative reform, to increase the available factual data base on which rational
      and efficacious reform proposals can be developed.

PMID- 7737860
TI  - Migraine consultations: a triangle of viewpoints.
AB  - Several studies have examined patients' attitudes to a consultation for migraine
      and other headaches. However, a patient's assessment of the problem for which
      they seek treatment may differ from that of the referring primary physician which
      may, in turn, differ from the specialist's. This study set out to examine this
      triangle. The commonest reason for referral was failure of treatment response.
      This contrasted with the patient's different perception--an increase in the
      frequency of attacks which we saw as headaches additional to migraine, accounting
      for failed treatment. Similarly, our view of the patient wanting reassurance
      paralleled their request for further information. These findings confirmed the
      hypothesis that recognizing and understanding a patient's fears were important
      factors towards a favorable outcome of a consultation.

PMID- 7737861
TI  - Extratrigeminal ice-pick status.
AB  - We describe six patients with an identical type of headache, consisting of short
      episodes (lasting around 1 week) of daily attacks of ice-pick-like pain,
      recurring every minute in the same points of the scalp. In all of them, the pain
      was felt outside the cutaneous area of the trigeminal nerve (retroauricular,
      parietal, and occipital regions). All patients were examined in the emergency
      department of a general hospital over a period of 7 years because of these acute
      headaches. None of them had a history of migraine. Although this pain is
      identical to idiopathic stabbing headache, it differs from it by its temporal
      profile (in "status"), its posterior (extratrigeminal) location, and its lack of
      association with migraine. While the bouts were usually severe and recurred in
      two patients, all had a self-limited benign course and responded promptly to
      indomethacin.

PMID- 7737862
TI  - Chronic paroxysmal hemicrania: dissociation of the pain and autonomic features.
AB  - The case of a woman suffering from chronic paroxysmal hemicrania is presented.
      Most attacks were unilateral and recurred on the same side. On a few occasions,
      attacks were observed on the contralateral side. In addition, the patient
      reported some incomplete attacks on the usually symptomatic side with autonomic
      phenomena, but without pain. That "partial" attacks would exist has been
      suspected on theoretical ground. This is, however, the first time such attacks
      have been reported by a patient. Therefore, a double dissociation of the
      symptomatology seemed to exist: (1) a side shift of attacks, and (2) incomplete
      ("partial") attacks. These unexpected findings occurred after two indomethacin
      treatment withdrawals. A possible central and "midline" origin of attacks or an
      indomethacin after-effect or both are discussed as a likely explanation for such
      a dissociation of symptoms and signs.

PMID- 7737863
TI  - Transnasal butorphanol in the treatment of acute migraine.
AB  - We studied transnasal butorphanol (Stadol NS) for pain relief during acute
      migraine in a multicenter, randomized, double-blind, placebo controlled trial
      using ambulatory patients at 10 geographically diverse headache centers. Patients
      were volunteer adults diagnosed with migraine with or without aura by
      International Headache Society criteria. One hundred fifty-seven patients
      completed the study. We treated the pain of one headache in each patient with
      either transnasal butorphanol (n = 107) or transnasal placebo (n = 50). Pain
      relief, pain intensity, nausea, vomiting, and effect on function were measured
      periodically. Adverse experiences were documented. Global assessments were made
      at follow-up. With butorphanol, migraine pain was reduced from moderate, severe,
      or incapacitating to slight or absent for 35 patients (33%) within 30 minutes,
      for 50 patients (47%) within 1 hour, and for 76 (71%) within 6 hours, compared to
      2 (4%), 8 (16%) and 15 (30%) respectively for placebo. Side effects were
      prominent, though confounded by the migraine. The most common side effects,
      compared to placebo, were dizziness (58% vs 4%), nausea and/or vomiting (38% vs
      18%), and drowsiness (29% vs 0%). We conclude that transnasal butorphanol is a
      useful analgesic for the pain of acute migraine. Its prominent side effects and
      low self reinforcement rate may limit its usefulness in some patients, while
      increasing its appropriateness for others.

PMID- 7737864
TI  - Migraine and concomitant symptoms among 8167 adult twin pairs.
AB  - We studied the inheritance of migraine and concomitant symptoms among 2690
      monozygotic (1524 female and 1166 male) pairs and 5497 dizygotic (2951 female and
      2546 male) twin pairs. Our material consists of a population-based questionnaire
      study among Finnish twins in 1981. The definition of migraine is based on a
      questionnaire method. Concordance was assessed using probandwise concordance
      rates and tetrachoric correlations for monozygotic (MZ) and dizygotic (DZ) twin
      pairs. For estimating the contribution of genetic factors to the susceptibility
      of migraine, a polygenic multifactorial model was used. Structural equation
      models were applied for estimating variance components and to compare different
      genetic models. Nearly one-half (40% to 50%) of the liability to migraine is
      attributable to genetic factors. In all structural analyses, the model with both
      additive genetic and unshared environmental component had the best goodness-of
      fit value. The genetic component varied between 34% to 51% in different migraine
      types. There were no remarkable differences between sexes except in the effects
      due to dominance, where the proportion was 26% for men and 14% for women.
      Concomitant symptoms among subjects within pairs concordant for headache had
      genetic effects varying from 56% (subjects with unilaterality) and 56% (subjects
      with visual symptoms) to 45% (persons with nausea and vomiting). The two
      threshold model of headache points to the continuum model of headache, and the
      thresholds represent different levels of severity of the pain. Our results
      emphasize a multifactorial and higher than previously reported genetic pattern in
      the etiology of migraine. Also unshared environmental factors play an important
      role.

PMID- 7737865
TI  - Rapid and sustained relief of migraine attacks with intranasal lidocaine:
      preliminary findings.
AB  - In a noncontrolled study, 23 migraine headache patients were treated with
      intranasal instillation of 0.4 mL of a 4% lidocaine solution during attacks of
      varying intensities. Evaluated were pretreatment and posttreatment changes in
      pain intensity, nausea, and side effects. Posttreatment intensity ratings
      significantly improved over pretreatment ratings, as determined by a Sandler A
      analysis (0.077; P < .0005). Migraine attacks were aborted in 12 of 23 patients,
      of which 8 were completely relieved within 5 minutes. In no case did an aborted
      attack return to more than a dull level within 24 hours, as determined by follow
      up telephone calls. A successful response of migraine attacks to lidocaine
      treatment was more apt to occur in patients having migraine solely, when compared
      to migraine patients who also had daily dull headaches; the difference was not
      significant. Unilateral attacks, however, were significantly more treatment
      responsive when compared to bilateral attacks (X2 = 3.85; P = .05). Nausea,
      associated with migraine attacks in 6 of 12 responders, was similarly aborted by
      lidocaine in 5 of 6 patients. Other side effects included mild nasal and eye
      burning of short duration (seconds), and oropharyngeal numbness of approximately
      20 minutes' duration. Despite the abrupt and absolute relief of migraine attacks
      afforded by lidocaine in most of our study patients, its level of efficacy awaits
      results of double-blind, placebo-controlled studies. Our findings raise new
      questions regarding the differential pathogenesis of migraine and cluster
      headache attacks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7737866
TI  - Intranasal lidocaine for cluster headache.
AB  - Thirty male patients with cluster headache were given 4% lidocaine solution to
      use intranasally as an abortive therapy. Four sprays of lidocaine were used
      ipsilateral to the pain, and two more were used, if necessary. Twenty-seven
      percent of the men reported moderate relief, 27% obtained mild relief, and 46%
      stated that they had no relief from the lidocaine, Side effects were minimal. In
      this study, intranasal lidocaine was only a marginally helpful therapy for
      cluster headache. However, because of the ease of administration and lack of side
      effects, lidocaine may remain worthwhile as an adjunctive medication.

PMID- 7737867
TI  - Specificity and sensitivity of temporalis ES2 measurements in the diagnosis of
      chronic primary headaches.
AB  - We have evaluated the specificity and sensitivity of temporalis ES2 measurements
      for the diagnosis of primary headaches. Ninety-four outpatients diagnosed
      according to IHS criteria were prospectively included: 25 had chronic tension
      type headache (code 2.2.), 15 episodic tension-type headache (code 2.1.), 20
      migraine without aura (code 1.1.) and 34 chronic daily headaches with daily
      analgesics/ergotamine abuse (code 8.2.). In chronic tension-type, the sensitivity
      of the ES2 test was 84% at the 0.1 and the 0.5 Hz, but only 56% at the 2Hz
      stimulation rates. Its specificity was 100% at 0.1Hz, 90% at 0.5Hz and 95% at 2Hz
      compared to migraine; positive predictive values were at similar levels.
      Sensitivity of ES2 at 0.1 Hz was 67% in episodic tension-type headache, but its
      positive predictive value versus migraine was excellent. Comparing chronic
      tension-type headache and analgesic abusers, the specificity and positive
      predictive value of the ES2 test for diagnosing chronic tension-type headache
      were less satisfactory (60%) while the negative predictive values, however,
      remained good (83% at 0.1Hz). The results confirm that the temporalis ES2 test
      has a higher diagnostic sensitivity in chronic and episodic tension-type
      headache, but that it has a high negative predictive value for both types of
      tension-type headache compared to other primary headaches. For diagnostic
      purposes, the 0.1Hz stimulation rate seems optimal. The 2Hz stimulation rate is
      the least sensitive, although it may induce total disappearance of ES2 in up to
      40% of patients. ES2 is of limited usefulness for separating chronic tension-type
      headache and chronic drug-abuse headache, possibly because the latter group
      comprises both tension-type headache and migraine patients.

PMID- 7737868
TI  - Site specificity of pain and tension in tension-type headaches.
AB  - Previous studies have not found a significant correlation between location of
      pain and electromyogram levels in chronic headache patients. However, these
      studies only examined a limited number of muscle groups and did not assess
      subjective tension levels. The present study evaluated a group of tension-type (n
      = 43) and migraine and tension-type (n = 30) headache patients. Measures were
      obtained at five muscle sites (frontalis, temporalis, masseter, splenius capitis,
      and trapezius) for patient ratings of headache pain, patient ratings of muscle
      tension, and electromyogram recording cross-sectionally. Neither subjective pain
      nor tension ratings were found to be significantly related to electromyogram
      levels. The site-specificity relationship between chronic headache pain,
      subjective report of muscular tension, and electromyogram levels remains unclear.

PMID- 7737869
TI  - Headache and cysticercosis in Ecuador, South America.
AB  - Intractable headaches have been described as the presenting complaint of many
      patients with T. solium neurocysticercosis. We conducted a house-to-house
      neuroepidemiological survey of 2,723 residents of an Andean community, known to
      be endemic for this infection. Migraine headaches were confirmed in 187 cases
      (68.7 per thousand), and tension headaches were diagnosed in 77 cases (28.3 per
      thousand). Fifty-seven migraine sufferers accepted computed tomography
      examination, and in 19 it revealed neurocysticercosis. In 11 out of 52
      migraineurs who had their blood drawn, electron immunotransfer blot testing
      (EITB) was positive for anticysticercal antibodies. In a computer-generated
      random sample of this community, 109 headache-free individuals were examined by
      CT, and 87 had EITB. Of the 109 subjects examined by CT, 14 were positive for
      cysticercosis. Of the 87 individuals tested by EITB, 7 were positive. A
      statistically significant difference between the symptom-free general population
      and the migraine patients was obtained for both CT (odds ratio 3.39, P < 0.005)
      and EITB (odds ratio 3.07, P < 0.05) diagnosis of neurocysticercosis.
      Neurocysticercosis appears to be a significant risk factor for the presentation
      of migraine-type headaches in areas endemic for T. solium infection.

PMID- 7737870
TI  - Postoperative headache in acoustic neuroma.
AB  - Recently, it has become obvious that disabling postoperative headache is a major
      problem with acoustic neuroma surgery. A questionnaire was used to
      retrospectively evaluate the incidence, clinical features, prognosis and possible
      therapeutic measures of this particular form of headache. Forty-two percent (42%)
      of patients had some headache prior to surgery but this was not a major
      complaint. After surgery, 75% of patients experienced headache. Only 24% had
      complete relief of headache. A very gradual improvement of the pain occurred in
      32%. Pathogenesis remains unclear, but clinical characteristics of the headache
      suggest a combination of tension-type, neuralgic and vascular components.
      Postoperative pain occurs mostly around the surgical site suggesting that this
      type of headache is the result of surgical trauma. A prospective long-term study
      is needed to delineate this condition further. Some therapeutic suggestions are
      offered.

PMID- 7737871
TI  - Nurse or doctor: biometry for intraocular lens power calculation, who should
      measure?
AB  - Biometry for intraocular lens power calculation is critical to the refractive
      success of cataract surgery with intraocular lens implantation. The majority of
      ophthalmology departments in Scotland currently entrust this procedure to junior
      medical staff. In an attempt to streamline preoperative assessment of cataract
      patients we have changed our practice so that nurses now carry out biometry. This
      prospective study, in which the results of 336 eyes undergoing cataract surgery
      and intraocular lens implantation were examined, shows that appropriately trained
      nursing staff in our department are able to perform the measurements for biometry
      at least as accurately as junior medical staff.

PMID- 7737872
TI  - Audit of parenteral antimicrobial agents and infusion fluids.

PMID- 7737873
TI  - An audit of clinical dependency in geriatric continuing care.
AB  - 1,376 elderly patients in 16 separate geriatric medical continuing care
      facilities, in greater Glasgow, including an NHS funded partnership nursing home,
      were surveyed over a six month period. This provided a snapshot of physical and
      mental dependency, specialist medical and nursing requirements and suitability of
      placement. The survey confirmed an extremely dependent population, with 82%
      scoring eight or less on a modified Barthel scale (maximum score 20) and 79%
      thought to require ongoing consultant supervision. Not all of the latter group
      were in the most dependent category. Forty one per cent of patients received
      specialised pressure relieving equipment and 30% had had a major adverse medical
      event in the six months prior to survey. Eighty-eight per cent of cases had had
      formal consultant review in the previous month. Currently there is a small group
      of patients resident within NHS continuing care facilities who might be cared for
      elsewhere. There is a larger group who need specialised care, they are
      characterised by a need for specialised nursing skills, regular medical review
      and consultant supervision.

PMID- 7737874
TI  - A review of influenza immunisation in Lothian.
AB  - OBJECTIVES: To assess the influence of the Chief Medical Officer's annual
      guidelines on influenza immunisation and to estimate vaccine uptake particularly
      of those resident in long-stay residential facilities and of other recommended at
      risk groups. DESIGN: Postal questionnaires. SETTING: Lothian, Scotland
      (population 750,000). SUBJECTS: All consultants caring for patients in long stay
      National Health Service facilities; a random sample of all general practitioners
      (GP's) in Lothian; managers/charge nurses of all local authority, private and
      voluntary long stay facilities in Lothian and continuing care facilities in the
      National Health Service including adults and children. MAIN OUTCOME MEASURES:
      Number (%) of general practitioners offering influenza vaccine to at-risk groups
      as defined in the Chief Medical Officer's guidelines; number (%) of hospital
      consultants caring for long-stay patients in hospital in Lothian who offer
      influenza vaccine to the same at-risk groups; percentage of long-stay
      residents/patients who received influenza vaccine in 1992-3. RESULTS: Seventy
      nine (75%) GPs said they offered influenza vaccine to all at-risk groups; 15
      (14%) GPs said they did not care for patients in long-stay facilities but offered
      vaccine to the other at-risk groups; 12 (11%) GPs who did have long-stay
      residents on their list, offered vaccine to some of them only and to all other at
      risk groups; 14 (56%) hospital consultants did not offer influenza vaccine to
      long-stay patients; 10 (40%) immunised only those at risk from chronic medical
      conditions if their quality of life was good; 1 (4%) consultant offered vaccine
      to all long-stay patients. In the winter of 1992-3, the mean proportion of
      residents immunised in private nursing homes was 65%, in residential homes 68.5%,
      and in long-stay National Health Service wards 4.5%. GPs commented that annual
      publicity was confusing for the public, vaccine was not available at the right
      time and there was uncertainty on the efficacy of the vaccine. Hospital
      consultants were reluctant to immunise patients with a poor quality of life or
      who were demented and unable to give consent. CONCLUSIONS: A large majority of
      GPs followed official advice and offered influenza vaccine to long-stay patients
      and other at risk groups. Hospital consultants offered influenza vaccine only to
      a small proportion of their long-stay patients, primarily those with a good
      quality of life.

PMID- 7737876
TI  - From the Chief Medical Officer.

PMID- 7737875
TI  - Medical telematics and telemedicine: an agenda for research evaluation in
      Scotland.

PMID- 7737877
TI  - A survey of information supplied to day-case patients.
AB  - The communication of information to day-case patients regarding post-anaesthetic
      precautions was reviewed. Deficiencies in the existing provision of information
      were identified and a proposal to improve on this is developed.

PMID- 7737878
TI  - A survey of patient attitudes towards an evening out-patient appointment.
AB  - A survey of patient preferences regarding out-patient appointment times was
      carried out in the C.T. Scanning unit at the Royal Infirmary, Edinburgh and the
      acceptability of receiving an evening appointment was assessed. Two hundred and
      eleven patients were questioned. One hundred and eighty-nine (90%) expressed
      satisfaction with their appointment. Fifty-nine (29%) preferred a morning
      appointment, forty (20%) an afternoon appointment but eighty-four (42%) expressed
      no preference. Forty-two patients (20%) expressed a wish to have an evening
      appointment, the most popular time being between 6.00 pm and 8.00 pm. If an
      evening appointment were given, 78% said they would accept it. Patients gave
      family, social and transport reasons for not preferring an evening appointment.

PMID- 7737879
TI  - Day care for the elderly mentally ill: diurnal confusion?

PMID- 7737880
TI  - FluoroScan mini C-arm unit.
AB  - Mini C-arm units are very compact, mobile fluoroscopic imaging systems designed
      for real-time imaging of the extremities (e.g., fingers, arm, foot). As with
      conventional mobile C-arm units (such as those we evaluated in Health Devices
      19[8], August 1990, and 22[3], March 1993), the standard environment in which
      mini C-arm units are used is the operating room; however, these units are compact
      enough to be used in emergency departments, physicians' offices, and, in some
      cases, locations outside of a healthcare facility (e.g., athletic playing field,
      work site). While mini C-arm units share many characteristics with conventional
      mobile C-arm units, their smaller size, simplicity of use, and lower cost can be
      significant advantages for certain procedures. In this study, we evaluated the
      FluoroScan, one of the two mini C-arm units currently available in the United
      States (and marketed worldwide). We tested this system against all relevant
      criteria from our earlier Evaluations of conventional mobile C-arm units and
      rated it Acceptable. Our ratings of C-arm units, in this and the previous
      studies, are based on the ability of a system to reliably produce the best
      possible image quality while (1) delivering the lowest possible radiation
      exposure to the patient and personnel and (2) minimizing operator effort and
      inconvenience. We discuss the purpose and use of mini C-arm units and describe
      the function of their major components in the Clinical and Technical Overview. In
      the Purchasing Guidance section, we highlight the differences between
      conventional and mini C-arm units and provide guidance for choosing the type of
      system that best meets a facility's needs. We also briefly describe the other
      currently available mini C-arm unit, the XiTec XiScan, and compare it with the
      evaluated unit. Issues of minimizing occupational radiation exposure resulting
      from scatter are discussed in the supplementary article, "Scatter Radiation from
      the FluoroScan Mini C-arm Unit." Readers are cautioned not to base purchasing and
      use decisions on our rating alone, but on a thorough understanding of our
      conclusions and the issues surrounding mini C-arm units, which can be gained by
      reading this study in its entirely. For additional perspectives on fluoroscopy
      and the operation of C-arm units, refer to our earlier Evaluations of
      conventional C-arm units.

PMID- 7737881
TI  - Understanding and implementing hospital information systems.
AB  - One of a hospital's greatest resources is its information. The hospital's
      information system, whether computerized or manual, is the means by which data is
      collected, integrated, and retrieved. However, because optimal patient treatment,
      financial management, and hospital operation require that decisions be based on
      current, accurate, complete, and well-organized data, a computerized hospital
      information system (HIS), when correctly implemented, can be the most effective
      means of disseminating valuable information to decision makers. Although the
      systems currently in place in most hospitals are used primarily to manage
      finances, an integrated HIS is much more than a financial system; it can, in
      fact, coordinate all of a hospital's information needs. An integrated HIS
      develops over time, typically several years. Merely automating existing
      procedures may not provide many of the potential benefits of a new system and may
      even carry forward most of the drawbacks of the old system. Determining how
      information is currently processed in the hospital and putting together an
      effective team to carry out acquisition and implementation of an HIS must precede
      the purchase of computers, networks, and software applications. In Part 1 of this
      article, we describe hospitals' general information needs and provide an overview
      of the current state of HISs and what hospitals can expect to gain from
      implementing a new system; in Part 2, we describe the steps hospitals can take
      when putting the system in place. We caution readers that, although we will be
      discussing many benefits of successful HISs, little documented or quantified
      evidence exists to show that these benefits are being realized; most evidence is
      subjective and qualitative, and claims are not thoroughly substantiated. Few, if
      any, hospitals have achieved the completely integrated system model--or even come
      close. Nevertheless, this article provides the groundwork for hospitals to make a
      thoughtful beginning. In upcoming issues, we will be publishing further articles
      in our information systems series. Also see our extensive Guidance Article on
      Laboratory Information Systems in Health Devices 23(10-11), October-November
      1994. ECRI will also be increasing the number of reports on information systems
      in its Healthcare Product Comparison System.

PMID- 7737882
TI  - Improper cassette attachment allows gravity free-flow from SIMS-Deltec CADD
      series pumps.

PMID- 7737883
TI  - Misconnection of vitrectomy handpieces and vitrectomy units.

PMID- 7737884
TI  - Damaged Abbott Pain Management Provider Ambulatory PCA pumps inaccurately
      indicate drug delivery.

PMID- 7737885
TI  - Does Drosophila melanogaster use ethanol as an energy source during starvation?
AB  - The influence of starvation on activities of three enzymes (ADH, ODH and alpha
      GPDH) was studied in Drosophila melanogaster. The changes were compared in two
      inbred lines which had different allelic combinations at the Odh and Aldox loci.
      We also studied the effect of ethanol on media which contained no sucrose
      ("starvation conditions"). The results show that there are large differences in
      the larval and adult alcohol utilization. The alcohol content of the medium, in
      the absence of sugar, appeared to be toxic for the larvae, while the adults
      appeared to utilize it as an energy source. The two strains differed little in
      their responses to starvation or to the ethanol treatment applied under
      starvation conditions. We conclude that the degree of toxicity of ethanol is
      highly dependent on the presence of sucrose.

PMID- 7737886
TI  - The influence of the Odh-Aldox region of the third chromosome on the response of
      Drosophila melanogaster to environmental alcohol.
AB  - Second instar larvae of Drosophila melanogaster were exposed to exogenous
      alcohol, which is known to influence the activities of several enzymes. In this
      study, the activity changes were followed in four enzymes (ADH, ODH, alpha GPDH
      and AOX) during ethanol exposure and compared in three inbred lines that had
      different allelic combinations at the Odh and Aldox loci. The results indicate
      that the Odh-Aldox region of the third chromosome may alter the general response
      to ethanol. The activity of ADH increased considerably in two strains in the
      larval stages in the presence of alcohol; nevertheless, strain 1, with the OdhS
      AldoxF allelic combination, showed a delay in the ADH induction compared to
      strain 2, which had the OdhF-AldoxS combination. In strain 3 (OdhS*-AldoxS)
      larvae, ADH induction by environmental ethanol was not detected. Moreover, the
      activities of alpha GPDH and AOX in strains 2 and 3 were not affected by ethanol.
      In contrast, the activities of all four enzymes in strain 1 changed after
      exposure to ethanol.

PMID- 7737887
TI  - Screening of toxicity and genotoxicity in wastewater by the use of the Allium
      test.
AB  - Wastewater was collected from two municipal wastewater treatment plants and
      twelve different industries representing five lines of business (chemical,
      metallic, petrochemical, pulp- and paper, and textile dye industries). Effect on
      the growth of Allium roots was measured after five days of exposure. Growth
      inhibition values, EC50 and EC30, showed no toxic effect for eight of the
      fourteen plants. The most toxic effect was found in wastewater from one of the
      pulp- and paper plants. Allium root tip cells were analyzed for chromosome
      aberrations after 24 h of exposure. Wastewater from nine of the fourteen plants
      was able to induce chromosome aberrations at a statistically significant level.
      The textile dye industry was the only line of business which did not show any
      genotoxic effect. Three of the plants (municipal wastewater, metallic, and pulp-
      and paper) showed genotoxicity in spite of being nontoxic in the growth
      inhibition experiment.

PMID- 7737888
TI  - Using isoelectric focusing to discern enzyme variation in northeast Atlantic
      stocks of the harp seal (Phoca groenlandica).
AB  - Liver and/or muscle samples were collected from harp seals on the breeding and
      moulting grounds in the White Sea area (N = 316) and in the Greenland Sea (N =
      225). Of a total of 25 presumptive loci detected by isoelectric focusing on
      polyacrylamide gels (IFPAG), 11 were variable. Of these, 4 were polymorphic at
      the 95% level, another 2 at the 99% level. The study shows that the higher
      resolving capacity obtained by IFPAG, as compared to starch gel electrophoresis,
      increases the number of electrophoretically detectable polymorphic loci in this
      species. The paper also compiles a set of methodical modifications which adapt
      IFPAG to large scale multilocus screening. The study indicates no marked
      differences between the White Sea and Greenland Sea stocks in frequency
      distributions of the consistently resolved enzyme systems. Other evidence
      suggests that potential exchange of genetic material between Northeast Atlantic
      harp seal stocks may still be so limited that for management purposes the stocks
      may be regarded as separate and self-sustaining units.

PMID- 7737889
TI  - An assessment of the relationships among species of Camelidae by satellite DNA
      comparisons.
AB  - Tandem satellite arrays and interspersed repetitive DNA components of the New
      World camelids guanaco, llama, alpaca, and vicuna and the Old World bactrian
      camel have been identified and compared. Southern hybridizations, using camel
      restriction fragments as probes, indicated that satellite DNAs in all camelids
      examined have been conserved since the last common ancestor about 5-10 MY ago.
      The hybridization profiles, however, varied from totally identical (MspI-sat) to
      highly differentiated (PstI-sat and EcoRI-sat) between Old and New World species.
      Repetitive DNA patterns specific of South American camelids were identified by
      most of the vicuna and guanaco probes and (a) llama and guanaco have
      undifferentiable patterns, supporting the view that the former is a domesticated
      form of the latter; (b) vicuna patterns were species-specific and in agreement
      with its position in a separate taxonomic unit; (c) the presence in alpaca of
      BamHI, TaqI and EcoRI patterns that are intermediate between those of the species
      above, suggested that the origin of the alpaca may be found in a cross-breed
      between the guanaco and vicuna.

PMID- 7737890
TI  - Bovine synteny group U7, previously assigned to G-banded chromosome 25 in the
      ISCNDA nomenclature, assigns to R-banded chromosome 29.
AB  - Four microsatellite-containing bovine cosmids have been regionally localized by
      fluorescence in situ hybridization to bovine R-banded chromosome 29 (BTA29) and
      to the 1;29 translocated chromosomes. PCR-analyses of a somatic hybrid cell panel
      assigned the four microsatellites to synteny group U7. One of the cosmids
      (IDVGA7) has been previously mapped to G-banded BTA25 allowing to assign U7 to
      this chromosome. Hence, it is concluded that G-banded BTA25 corresponds to R
      banded BTA29. The occurrence of other misleading nomenclatures for small bovine
      chromosomes is discussed.

PMID- 7737891
TI  - Linkage disequilibrium in Hungarian populations of Drosophila melanogaster.

PMID- 7737892
TI  - Effect of dissolved oxygen levels on biosynthesis of aureofungin by
      Streptoverticillium cinnamoneum var. terricola.
AB  - Biosynthesis of aureofungin by Streptoverticillium cinnamoneum var, terricola was
      found to be an oxygen dependent reaction. An accelerated rate of aureofungin
      production, along with a better yield coefficient were obtained under conditions
      of enhanced aeration during fermentation. A higher oxygen transfer rate was found
      to stimulate aureofungin A, and suppresses aureofungin B formation.

PMID- 7737893
TI  - Preliminary studies on a Streptomyces sp. CS-14 showing broad spectrum antibiotic
      activity.
AB  - A Streptomyces sp. CS-14 producing antifungal and antibacterial antibiotics has
      been isolated and characterized. The characterization of mycelial bound
      antibiotic revealed the presence of a hexaene polyene macrolide whereas filtrate
      bound antibiotic belonged to aminoglycoside group. Both the antibiotics showed
      very good antimicrobial activities in vitro.

PMID- 7737894
TI  - Regulatory enzymes for the screening of streptomycin producing mutant strains of
      Streptomyces griseus.
AB  - Intermediary enzymes of streptomycin biosynthesis-arginine amidinotransferase and
      alkaline phosphatase were located at the early fermentation stages. Their
      relationship with streptomycin production by Streptomyces griseus strains GX-19
      and MR-20 was determined and the use of this relationship was made for the
      screening of streptomycin producing mutant strains.

PMID- 7737895
TI  - Synthesis, physico-chemical and biological properties of some alkali metals and
      quaternary alkylammonium salts of polyene antibiotics: amphotericin B, nystatin
      and aureofungin.
AB  - Polyene antibiotics are known for their remarkable antifungal properties. The
      alkali metal and quaternary alkylammonium salts of amphotericin B, nystatin and
      aureofungin have been prepared by ion-exchange method. The physico-chemical and
      biological properties of these salts have been studied with a view to evaluate
      their therapeutic advantages over the parent compounds. While the majority of the
      salts reported herein showed more water solubility; triethylammonium salts,
      unlike the other alkali metal salts, possessed marginally improved or similar
      bioactivity in comparison to their parent antibiotic having reduced toxicity.

PMID- 7737896
TI  - Effect of different fractions of petroleum ether (60-80 degrees) extract of the
      seeds of Lagerstroemia speciosa (Linn. ex Murray) Pers. on some microorganisms.
AB  - In a model experiment, seed extracts were applied to different bacterial test
      organisms. Different fractions of seed extracts in petroleum ether (60-80 degrees
      C) of Lagerstroemia speciosa (Linn. ex. Murray) Pers. when applied to both Gram
      positive and Gram negative test bacteria, some fractions showed high antagonistic
      activity.

PMID- 7737897
TI  - Dermostatin A and B: chromatography, structural and configurational studies using
      HPLC, CCD, 13C (125 MHz) and 1H (500 MHz) NMR spectroscopy.
AB  - HPLC of crude Dermostatin indicated presence of three pairs of components. Hence,
      attempts were made to purify Dermostatin. Purification of crude Dermostatin has
      been carried out using column chromatography and counter current distribution
      methods. Each of these fractions were tested for activity. The major fraction
      which showed greater activity was taken for the preparation of Dermostatin nona
      acetate. Structural characterisation of Dermostatin nona-acetate has been carried
      out using UV-visible spectroscopy in different solvents to obtain the
      characteristic spectrum of a carbonyl conjugated hexaene at room temperature.
      Structural and configurational studies of Dermostatin nona-acetate using 500 MHz
      1H NMR and 125 MHz 13C NMR has been used in the assignment of various functional
      groups in Dermostatin A and B as well as to provide corroboration to the earlier
      structural elucidation.

PMID- 7737898
TI  - The development of helical computed tomography.

PMID- 7737899
TI  - Increased prevalence of HTLV-I infection in patients with hepatocellular
      carcinoma associated with hepatitis C virus.
AB  - The progression from chronic hepatitis C virus (HCV) infection to hepatocellular
      carcinoma (HCC) has been reported. We evaluated whether co-infection with the
      human T-lymphotropic virus type I (HTLV-I) might be associated with this
      transition in a cross-sectional analysis of 127 patients with HCV-chronic
      hepatitis (mean age = 51.7) and 43 patients with HCV-associated HCC (mean age =
      62.4); the seroprevalence of anti-HTLV-I was 9.5% and 30.2%, respectively. For
      subjects 50 years or older, the seroprevalence of anti-HTLV-I in HCC patients was
      13/41 (31.7%) which was significantly higher than that in chronic hepatitis
      patients (6/82, 7.3%) (P = 0.001). The relative risk (RR) of association was 12.8
      (P = 0.0004) among the males, however, no association was evident among the
      females, RR = 1.3 (P = 0.80). The increased prevalence of HTLV-I positivity among
      the HCC cases could not be attributed to a higher rate of prior transfusion.
      These data suggest that co-infection with HTLV-I may contribute to the
      development of HCC among patients with HCV-induced chronic liver diseases in a
      highly HTLV-I-endemic area.

PMID- 7737900
TI  - Regional mapping of two subunits of transcription factor E4TF1 to human
      chromosome.

PMID- 7737901
TI  - A pharmacokinetic and pharmacodynamic analysis of CPT-11 and its active
      metabolite SN-38.
AB  - In the present study, an attempt was made to determine the precise
      pharmacokinetics of 7-ethyl-10-[4-(1-piperidino)-1
      piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10
      hydroxycamptothecin (SN-38). The relationship between pharmacokinetic parameters
      and pharmacodynamic effects was also investigated to elucidate the cause of
      interpatient variation in side effects. Thirty-six patients entered the study.
      CPT-11, 100 mg/m2, was administered by IV infusion over 90 min weekly for four
      consecutive weeks. The major dose-limiting toxicities were leukopenia and
      diarrhea. There was a positive correlation between the area under the
      concentration-time curve (AUC) of CPT-11 and percent decrease of WBC (r = 0.559).
      On the other hand, episodes of diarrhea had a better correlation with the AUC of
      SN-38 (r = 0.606) than that of CPT-11 (r = 0.408). Multivariate analysis revealed
      that the AUC of SN-38, AUC of CPT-11 and indocyanine green retention test were
      significant variables for the incidence of diarrhea and that both performance
      status and AUC of CPT-11 were significant variables for percent decrease of WBC.
      The large interpatient variability of the degree of leukopenia and diarrhea is
      due to a great plasma pharmacokinetic variation in CPT-11 or SN-38. The AUCs of
      CPT-11 and SN-38 obtained from the first administration of CPT-11 correlate with
      toxicities, but it is impossible to predict severe side effects before the
      administration of CPT-11 at the present time.

PMID- 7737902
TI  - Pharmacological correlation between total drug concentration and lactones of CPT
      11 and SN-38 in patients treated with CPT-11.
AB  - The pharmacokinetics of 7-ethyl-10-[4-(1-piperidino)-1
      piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10
      hydroxycamptothecin (SN-38), were examined to establish the pharmacokinetic
      variability of the active lactones of CPT-11 and SN-38 in comparison with that of
      the total (lactone and carboxylates) plasma CPT-11 and SN-38. Twelve patients
      with malignancies were entered in the study. All received 100 mg/m2 of CPT-11 by
      intravenous drip infusion over 90 min. Blood was sampled at 10 time points in
      heparin-containing syringes. Analysis by high-performance liquid chromatography
      showed that the ratio of CPT-11 lactone to total CPT-11 concentration was highest
      (66%) just after the end of infusion and gradually decreased to 30% at 24 h.
      Almost 70% of SN-38 lactone was detected after the end of infusion and this
      decreased to 50% within 24 h. The standard errors of percent lactone of CPT-11 of
      SN-38 to total drug concentration at each sampling point were less than 12%. The
      area under the concentration-time curve (AUC) of total CPT-11 and that of total
      SN-38 were significantly correlated with the AUCs of the lactone CPT-11 and those
      of lactone SN-38, respectively. We conclude that, for practical purposes,
      monitoring of total CPT-11 and SN-38 has essentially the same clinical
      significance as monitoring of lactone CPT-11 and SN-38.

PMID- 7737903
TI  - A limited sampling model for estimating pharmacokinetics of CPT-11 and its
      metabolite SN-38.
AB  - The objective of this study was to develop a limited sampling model (LSM) to
      estimate the area under the curve (AUC) of 7-ethyl-10-[4-(1-piperidino)-1
      piperidino]carbonyloxycamptothecin (CPT-11) and that of 7-ethyl-10
      hydroxycamptothecin (SN-38) as predictive pharmacokinetic variables for
      leukopenia and episodes of diarrhea induced by CPT-11 administration. The model
      was developed with a training set consisting of pharmacokinetic studies in 36
      patients who received a 90-min i.v. infusion of CPT-11 at a dose of 100 mg/m2. A
      multiple regression analysis of CPT-11 or SN-38 concentrations observed at each
      time point in the training set was used to predict the AUC of CPT-11 or SN-38.
      The final sampling models using only two time points were: AUCCPT-11 =
      3.7891*C2.5 + 14.0479*C13.5 + 1.5463 AUCSN-38 = 0.5319*C2.5 + 19.1468*C13.5 +
      72.7349 where C2.5 and C13.5 are the plasma concentration of CPT-11
      (micrograms/ml) or SN-38 (ng/ml) at 2.5 and 13.5 h after the initiation of CPT-11
      infusion, respectively. The models were validated prospectively on a separate
      test data set of 12 patients receiving the same dose of CPT-11 investigated in a
      previous study. Validation of the final LSM on the test data set gave values of
      root mean square error (RMSE) of 12.72% and 5.97% for the AUC of CPT-11 and that
      of SN-38, respectively. The model can be used to monitor the AUCs of both CPT-11
      and SN-38 for the early prediction of toxicities and to establish a
      pharmacokinetically based dose modification strategy for safe administration of
      CPT-11.

PMID- 7737904
TI  - Intracellular carboxyl esterase activity is a determinant of cellular sensitivity
      to the antineoplastic agent KW-2189 in cell lines resistant to cisplatin and CPT
      11.
AB  - KW-2189, a novel antitumor antibiotic belonging to the duocarmycins, possesses
      marked DNA-binding activity upon activation by carboxyl esterase to its active
      form, DU-86. Three duocarmycins, KW-2189, DU-86 and duocarmycin SA, were active
      against the cisplatin (CDDP)-resistant human non-small cell lung cancer cell
      lines PC-9/CDDP and PC-14/CDDP, and the multidrug-resistant human small cell lung
      cancer cell line H69/VP. However, HAC2/0.1, a CDDP-resistant human ovarian cancer
      cell line which is also resistant to CPT-11 because of decreased intracellular
      activation of CPT-11, was about 12.8-fold more resistant to KW-2189. HAC2/0.1 was
      not resistant to other duocarmycins as compared to its parental cell line, HAC2.
      There was no difference between HAC2 and HAC2/0.1 with regard to the
      intracellular accumulation of KW-2189. Addition of 130 mU/ml of carboxyl esterase
      to the culture medium did not influence the sensitivity of HAC2 cells to KW-2189.
      However, the sensitivity of HAC2/0.1 cells to KW-2189 was enhanced to the level
      of HAC2. These results suggest that HAC2/0.1 is less potent than HAC2 in
      activating KW-2189. The carboxyl esterase activity of whole-cell and microsomal
      extracts from HAC2/0.1 was approximately 60% of that from HAC2. The cell-free
      experiment revealed that KW-2189 bound to DNA more efficiently in the presence of
      HAC2 than HAC2/0.1 cell extract. It was concluded that decreased intracellular
      carboxyl esterase activity in HAC2/0.1 cells caused decreased intracellular
      conversion of KW-2189 to its active form, thus producing resistance to KW-2189.
      The decreased conversion of CPT-11 to SN-38 in HAC2/0.1 cells might be explained
      by decreased carboxyl esterase activity.

PMID- 7737905
TI  - Survival rates of childhood cancer patients in Osaka, Japan, 1975-1984.
AB  - Survival rates for childhood cancers were analyzed with a total of 2,209 cases
      who were registered in a population-based cancer registry in Osaka, Japan in 1975
      1984. These cases were reclassified according to Birch's classification and the
      survival rate of each diagnostic group was calculated by Kaplan-Meier methods.
      Death certificate-only cases, which amounted to 3.9% of all incidence, were
      excluded from the calculation. The five-year cumulative survival rate for both
      sexes was 46% for all cancer children. Among 12 major diagnostic groups, the most
      favorable survival was seen in retinoblastoma (87.5%), followed by renal tumors,
      epithelial neoplasms, and gonadal and germ-cell tumors. The outcome was
      unfavorable in leukemias, sympathetic nervous system tumors, hepatic tumors and
      malignant bone tumors. Comparing the survival in 1975-1979 with that in 1980
      1984, the rate for all childhood cancer rose from 41% to 51%. Improvement in
      survival was also observed in 4 groups; acute lymphocytic leukemia, acute non
      lymphocytic leukemia, non-Hodgkin's lymphoma and osteosarcoma. One attributable
      factor for the rise of survival was proved to be improvement of medical treatment
      by Cox's hazard model analysis. Comparison of survival rates in Osaka with those
      in England and the U.S. revealed that the prognosis for acute lymphocytic
      leukemia and acute non-lymphocytic leukemia was less favorable in Osaka than in
      England and the U.S.

PMID- 7737907
TI  - Genetic complementation of the immortal phenotype in group D cell lines by
      introduction of chromosome 7.
AB  - Human immortal cell lines have been classified into at least four (A-D) genetic
      complementation groups by cell-cell hybrid analysis, i.e., a hybrid derived from
      different groups becomes mortal. Recently we have demonstrated that introduction
      of human chromosome 7 suppresses indefinite division potential in the non
      tumorigenic human immortalized fibroblast lines KMST-6 and SUSM-1, both assigned
      to complementation group D. By extending our microcell-mediated chromosome
      transfer, we found that chromosome 7 also suppresses division potential in the
      human hepatoma line HepG2 (again, assigned to group D). Chromosome 7 was thus
      shown to suppress indefinite growth in the above group D cell lines irrespective
      of their cell types, or whether they are tumorigenic or not. Since chromosome 7
      had no such effect on representative cell lines derived from complementation
      group A, B or C, these results indicate that the senescence gene(s) commonly
      mutated in the group D cell lines is located on chromosome 7.

PMID- 7737906
TI  - Serum antibody against unfused recombinant E7 protein of human papillomavirus
      type 16 in cervical cancer patients.
AB  - Sera were examined for the presence of antibody against E7 protein of human
      papillomavirus type 16 (HPV-16) by Western blot analysis using the bacterially
      derived unfused protein. The occurrence rates of anti-E7 antibody against HPV-16
      were 14.1% (10/71) in cervical cancer patients, 0% (0/48) in cervical
      intraepithelial neoplasia patients, and 0% (0/41) in female non-malignant
      patients. Three patients (one with endometrial cancer, one with breast cancer,
      and one male patient with colon polyp) out of 115 patients with tumors in organs
      other than the cervix, had antibody against E7 protein of HPV-16. The serum
      antibody, once positive, could be detected for a long time after surgical removal
      of the cancers in all cases that could be followed up. HPV-16 DNA could be
      detected in 50% (13/26) of cervical cancer patients. Sixty-nine percent (9/13) of
      patients with HPV-16 DNA in cancers had the antibody and all the patients with
      stages II, III, and IV cervical cancer (8/8) harboring HPV-16 DNA showed the
      presence of the antibody against E7 protein of HPV-16. In contrast, only 20%
      (1/5) of cervical cancer patients with stage Ia or Ib harboring HPV-16 DNA showed
      positive for the anti-E7 antibody in sera. These findings suggest that the
      presence of anti-E7 antibody in serum depends on the staging of cervical cancer
      and extent of HPV infection.

PMID- 7737908
TI  - Inhibition of pulmonary metastases and tumor cell invasion in experimental tumors
      by sodium D-glucaro-delta-lactam (ND2001).
AB  - Sodium D-glucaro-delta-lactam (ND2001) inhibited spontaneous pulmonary metastases
      of the highly metastatic B16 melanoma variant with a maximal inhibition rate of
      99.5%, and 6 of 7 animals remained metastasis-free. Likewise, ND2001 inhibited
      the spontaneous pulmonary metastases of both Lewis lung carcinoma (3LL) with a
      rate of 98.0% (3 of 5 animals remaining metastasis-free) and rat KDH-8 liver
      carcinoma with a rate of 82.5% (3 of 7 animals remaining metastasis-free),
      although it was unable to inhibit the metastases of mouse BMT-11 fibrosarcoma and
      rat SST-2 breast carcinoma. Pretreatment with ND2001 in vitro inhibited the
      pulmonary metastases of the B16 variant and 3LL cells, which indicates direct
      action upon the cancer cells. When the invasive activity of cancer cells was
      measured by the Boyden chamber method, the number of invading B16 variant or 3LL
      cells was reduced with maximal inhibition rates of 93.0% or 89.9%, respectively,
      but pretreatment with ND2001 failed to reduce the invasive activity of BMT-11 or
      SST-2 cells. ND2001 showed neither cytocidal nor antitumor activity. These
      results suggest that ND2001 inhibited pulmonary metastases at the invasive step
      into the basement membrane by directly changing some property of the tumor cells.

PMID- 7737909
TI  - Localization of urokinase-type plasminogen activator, plasminogen activator
      inhibitor-1, 2 and plasminogen in colon cancer.
AB  - We examined the localization of urokinase-type plasminogen activator (u-PA),
      plasminogen activator inhibitors (PAI-1 and PAI-2) and plasminogen (plg) in 26
      cases of colon cancer by immunohistochemical staining. The u-PA antigen was
      detected in the cytoplasm of cancer cells (18/26) and stromal cells adjacent to
      cancer tissues (9/26). The localization of u-PA mRNA examined by in situ
      hybridization was consistent with that of u-PA antigen. The PAI-1 antigen was
      detected in fibroblasts and endothelial cells (22/26), while PAI-2 antigen was
      found in cancer cells (20/26). The plg antigen was seen in the extracellular
      matrix of the cancer stroma. The u-PA expression in cancer cells was
      significantly more frequently detected in cases with lymph node metastasis than
      in cases without metastasis. In either PAI-1- or PAI-2-expressing cases, lymph
      node metastasis seemed to be restrained. These findings indicate that cancer
      cells themselves produce u-PA, and suggest that u-PA converts plg into plasmin,
      which dissolves the extracellular matrix surrounding cancer cells, resulting in
      cancer invasion and metastasis. PAI-1 and PAI-2 may have inhibitory actions on
      cancer invasion and metastasis mediated by u-PA.

PMID- 7737910
TI  - Differing distribution of hepatocyte growth factor-positive cells in the liver of
      LEC rats with acute hepatitis, chronic hepatitis and hepatoma.
AB  - Using anti-rat hepatocyte growth factor (HGF) antibody, we investigated the
      distribution of HGF-positive cells in the liver tissues of LEC rats at various
      phases of liver diseases. During the phase of fulminant hepatitis, HGF-positive
      cells increased remarkably, and many of them were localized at the portal triads;
      these cells were identified from their shape as non-epithelial cells. A reduced
      number of HGF-positive cells was observed during the phase of chronic hepatitis,
      while no HGF-positive cells were seen in the tissue of cholangiofibrosis. During
      the phase of carcinoma, staining revealed that both the hepatocellular carcinoma
      cells and the non-epithelial cells in cancerous liver tissue were HGF-positive.
      These results suggest that, in LEC rats, HGF may play an important role in the
      regeneration of hepatocytes as well as in the development of hepatocellular
      carcinoma.

PMID- 7737911
TI  - p53 mutations occur in clinical, but not latent, human prostate carcinoma.
AB  - To elucidate the role of the p53 tumor suppressor gene in prostate tumorigenesis,
      we probed for mutations in latent and clinical prostate cancers using single
      strand conformation polymorphism (SSCP) and restriction fragment length
      polymorphism (RFLP) analysis in combination with direct gene sequencing and
      immunohistochemical methodologies. Fifteen cases of subclinical and 32 cases of
      clinical carcinoma, the latter graded in stages A through D, were available for
      study. While p53 point mutations were detected in only 5 of 32 (16%) clinical
      cancers, no mutations were detected in latent disease. Of the carcinomas in
      stages B, C and D, 15% (2/13), 29% (2/7) and 9% (1/11) were positive for p53
      mutations, respectively. Although no specific mutational patterns were observed,
      the aberrations found were predominantly single base missense substitutions. The
      data suggest not only an association of p53 mutation and progression of clinical
      prostate cancer, but also imply that some other mechanism(s) are at work in
      latent carcinoma.

PMID- 7737912
TI  - Helicobacter pylori infection, serum pepsinogen level and gastric cancer: a case
      control study in Japan.
AB  - We conducted a case-control study to evaluate the effect of Helicobacter pylori
      (HP) infection on the risk of gastric cancer in Tokyo, Japan. The sera at the
      time of diagnosis from 282 gastric cancer cases and 767 sex- and age-matched
      cancer-free controls were tested for the presence of anti-HP IgG antibody (HM-CAP
      ELISA kit) and serum pepsinogen (PG) level (PG I and PG II Riabead). No
      significant association was observed in all sets [matched odds ratio (OR) = 1.04,
      95% confidence interval: 0.73-1.49]. In subgroup analyses, however, an
      association was suggested in females [OR = 1.57], a younger population (< 50
      years) [OR = 1.86], early cancer [OR = 1.53] and small cancer (< 40 mm) [OR =
      1.55]. Furthermore, we observed a tendency for odds ratios to decrease with an
      increase in age or cancer growth (depth of tumor invasion and tumor size).
      Considering that the spontaneous disappearance of HP due to extended mucosal
      atrophy may lead to these decreasing odds ratios, we applied the conditional
      logistic model adjusted for the PG I/II ratio as a measure of atrophic gastritis.
      This analysis showed a positive association with HP infection in all sets [OR =
      1.69; 1.01-2.81], distal cancer [OR = 1.88; 1.07-3.31] and intestinal-type cancer
      [OR = 3.76; 1.39-10.18]. We concluded that the risk of cancer associated with HP
      infection may be underestimated in studies with cross-sectional exposure because
      of spontaneous disappearance of HP due to extended mucosal atrophy.

PMID- 7737913
TI  - Characterization of a novel human tumor necrosis factor-alpha mutant with
      increased cytotoxic activity.
AB  - Various novel recombinant human tumor necrosis factor-alpha (TNF) mutants were
      prepared using protein engineering techniques, and their cytotoxic activity was
      compared with that of the intact form of TNF (intact TNF). Mutant 471 (a TNF
      mutant molecule with the deletion of 7 amino acids at the amino-terminal and the
      substitution of Pro8Ser9Asp10 by ArgLysArg) had a 6-fold higher cytotoxic
      activity against murine L929 cells. The mutant TNF had an increased ability to
      bind to TNF receptor on murine L929 fibroblasts cells. A cross-linking study
      revealed that mutant 471 had an increased ability to form an active trimer.
      Mutant 471 also showed higher cytotoxic activity against human KYM myosarcoma
      cells and human MIA PaCa-2 pancreatic carcinoma cells. The possible cachectin
      activity of the mutant was almost the same as that of intact TNF. These results
      suggest that mutant 471 might be a more promising candidate as an anticancer
      agent than intact TNF.

PMID- 7737914
TI  - Human alveolar macrophages augment natural killer cell stimulatory factor
      (interleukin-12)-inducible killer activity from autologous blood lymphocytes.
AB  - Interleukin-12 (IL-12), also known as natural killer cell stimulatory factor
      (NKSF), was found to induce cytotoxic activity from human blood T cells and NK
      cells. The present study was undertaken to examine the effect of human alveolar
      macrophages (AM) on induction by IL-12 cytotoxic cells from blood lymphocytes. AM
      were obtained by bronchoalveolar lavage from healthy donors. Highly purified
      lymphocytes (> 99%) and monocytes (> 90%) were also isolated by centrifugal
      elutriation from peripheral blood of the same donors. Cytotoxicity of lymphocytes
      was measured by 4-h 51Cr release assay. IL-12 stimulated blood lymphocytes to
      produce interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha),
      and this effect was augmented by co-cultivation with monocytes or AM. AM
      upregulated induction of cytotoxic lymphocytes was stimulated with IL-12, and
      this effect was significantly abrogated by addition of antibodies against IFN
      gamma and TNF alpha. Induction by IL-12 of IFN gamma production and cytotoxic
      activity of CD8+ cells was also augmented by co-cultivation with monocytes or AM.
      AM were more effective than monocytes in augmenting the cytotoxic activity of IL
      12-stimulated lymphocytes and CD8+ cells. These observations suggest that in situ
      induction of IL-12-stimulated cytotoxic cells in the lung may be regulated by
      complex cytokine networks, depending on participation of monocytes and alveolar
      macrophages.

PMID- 7737915
TI  - Establishment and characterization of acquired resistance to platinum anticancer
      drugs in human ovarian carcinoma cells.
AB  - To investigate differences in resistance to cis-diamminedichloroplatinum(II)
      (CDDP) and diammine (1,1-cyclobutanecarboxylato)platinum(II) (CBDCA), and their
      newly developed derivative, ((-)-(R)-2-aminomethylpyrrolidine (1,1
      cyclobutanedicarboxylato)platinum (II) (DWA2114R), four types of resistant cell
      lines were established from a parental cell line (NOS2) of a serous
      cystadenocarcinoma of the ovary. The cross-resistance of CDDP-resistant cells
      (NOS2CR1 and NOS2CR2) to DWA2114R was slight (only 25% of the resistance to
      CDDP), and no cross-resistance was observed to anticancer drugs other than the
      CDDP derivative, except to camptothecin (CPT-11) in the case of NOS2CR2 cells.
      The cross-resistance of CBDCA-resistant cells (NOS2CBR) to DWA2114R was slight
      (only about 1/3 of the resistance to CBDCA), and no cross-resistance was observed
      among anticancer drugs other than the CDDP derivative. On the other hand,
      DWA2114R-resistant cells (NOS2DR) showed a high cross-resistance to CDDP, CBDCA,
      etoposide (VP-16), and CPT-11. Intracellular accumulations of CDDP and CBDCA were
      markedly reduced in NOS2CR1, NOS2CR2, and NOS2CBR cells compared to those in NOS2
      cells, but were reduced only slightly in NOS2DR cells. Intracellular accumulation
      of DWA2114R was reduced somewhat in the four types of resistant cells.
      Glutathione S-transferase activity was not increased in any of the four types of
      resistant cells, and intracellular GSH concentration was increased only in
      NOS2CR2 cells (by 2.6 fold). From these results, we consider that the resistance
      mechanisms against CDDP and CDBCA are similar, and reduction of intracellular
      drug accumulations is a significant factor. Resistance to DWA2114R differed from
      resistance to CDDP and CBDCA in both cross-resistance spectrum and resistance
      mechanism, indicating that reduction in intracellular drug accumulation is not
      the major resistance mechanism.

PMID- 7737916
TI  - Behavioral and electrophysiological responses to electrical stimulation in the
      cat. I. Absolute thresholds.
AB  - Estimates of electrical auditory brainstem response (EABR) thresholds are
      compared with behavioral thresholds for electrical stimulation in the same
      subject using identical stimuli and electrode configurations. Four cats were
      behaviorally trained to measure acoustic auditory thresholds using food as a
      reward in an operant reinforcement paradigm. One of the animals was then
      implanted, in an otherwise normal ear, with a scaled-UCSF multi-contact electrode
      array containing four intracochlear electrodes. Three animals were implanted with
      an electrode array containing eight intracochlear contacts and one extracochlear
      contact under the temporalis muscle following unilateral cochlear perfusion with
      10% neomycin solution. Stimuli for the behavioral studies were single
      presentations of 200 us/phase biphasic current pulses. For the EABR studies, the
      same stimulus was presented at a rate of 32/s. In general, for the animal with
      the four-contact array and two of the three subjects with the eight-contact
      implant, changes in electrode configuration produced well-differentiated changes
      in threshold. For these three subjects, comparisons of behavioral and EABR
      thresholds for the majority of monopolar and bipolar electrode configurations
      tested showed excellent agreement (r2 = 0.88). Correlations between behavioral
      and EABR measures in these animals were comparable for bipolar and monopolar
      arrangements (r2 = 0.88 for bipolar and 0.87 for monopolar). For one subject with
      the eight-contact electrode, who showed similar monopolar and bipolar electrode
      behavioral thresholds for all tested electrode spacings or configurations, most
      EABR thresholds were substantially higher than, and poorly correlated with,
      behavioral thresholds (r2 = 0.15; r2 = 0.28 for monopolar arrangements, and r2 =
      0.12 for bipolar arrangements).

PMID- 7737917
TI  - The changing microtubule arrangements in developing hair cells of the chick
      cochlea.
AB  - It has been suggested that microtubules in auditory hair cells might be involved
      in directing the morphological and hence functional polarisation of the sensory
      hair bundles. The distribution of microtubules was studied in hair cells of the
      chick cochlea, during the developmental stages when the stereocilia and cuticular
      plate were being formed. Cochleae were immunofluorescently labelled with
      antibodies to tubulin at specific stages in development, and hair cell
      ultrastructure was observed by electron microscopy. We found that the microtubule
      array changed from a simple symmetrical apical plate with a central kinocilium
      before the cuticular plate forms, to a ring with the kinocilium to one side when
      the cuticular plate begins to form, through to a cup-like arrangement below the
      cuticular plate once the plate has formed. In the earliest stages, no asymmetries
      were observed in the distribution of the microtubules, suggesting that structures
      other than the microtubules set up the functional polarisation of the
      stereociliary bundle.

PMID- 7737918
TI  - Cochlear microphonic measurements of interaural time differences in the chick.
AB  - The major cues for the sound localization are the interaural differences in the
      timing and intensity of acoustic information. This poses a difficult coding
      problem for animals with relatively small heads, such as birds, because
      interaural time differences (ITDs) would have a small range and magnitude and
      interaural intensity differences (IIDs) would be significant for only high
      frequency sounds. It has been suggested that this coding problem is mitigated in
      birds by an enhancement of ITDs and IIDs resulting from the acoustic coupling of
      the two middle ear cavities through an interaural canal. In this report, the
      functional ITDs for sounds at different azimuthal locations were recorded in
      young chicks, and the contribution of middle ear acoustic coupling was evaluated.
      ITDs were calculated from simultaneous cochlear microphonic (CM) recordings
      evoked by pure tone stimuli. These effective ITDs were larger than predicted by
      the physical separation of the two ears, and this enhancement was more pronounced
      at low (0.8 and 1 kHz) than at high (2 and 4 kHz) frequencies, reaching maximum
      values of approximately 180 and 100 microseconds, respectively. The amplitude of
      the CM also varied as a function of sound source location. This variation was as
      much as +/- 30%, even for the low frequency tones. This suggests that IID cues
      are also available to the chick. To determine the contribution of middle ear
      acoustic coupling to the timing and amplitude of the CM response, the CM in one
      ear was measured prior to, and following occlusion of the contralateral external
      auditory canal. The cochlear microphonic from the ear distal to the sound source
      advanced in time and increased in amplitude when the ear proximal to the sound
      source was sealed. These effects were more pronounced for low frequency sounds.
      These findings confirm that acoustic coupling of the middle ear cavities plays a
      role in enhancing sound localization cues in the chick.

PMID- 7737920
TI  - Cochlear frequency-place map in adult chickens: intracellular biocytin labeling.
AB  - A cochlear frequency-place map was developed for adult chickens by labeling
      cochlear ganglion neurons with biocytin and correlating the location of each
      labeled fiber along the basilar papilla with the characteristic frequency of the
      unit's tuning curve. Labeled fibers showed little or no branching within the
      sensory epithelium and most fibers appeared to terminate on a single hair cell
      along the neural side of the basilar papilla. The CFs of the labeled neurons
      ranged from 353 Hz to 3145 Hz and the location of the labeled neurons ranged from
      30.1% to 74.4% of the total distance from the apex of the papilla. CFs increased
      in an orderly manner from the apex towards the base of the papilla. The cochlear
      frequency map for adult chickens was similar to that estimated from previous
      cochlear lesion studies carried out on 30 day old chicks, although the predicted
      frequencies in the adults were slightly higher in some regions of the basilar
      papilla than in 30 day old animals. However, previous maps developed in young
      animals (< or = 21 days) using lesion or labeling data predict significantly
      lower frequencies for a given location than in adult animals particularly in the
      basal half of the cochlea.

PMID- 7737919
TI  - The effect of acoustic overexposure on the tonotopic organization of the nucleus
      magnocellularis.
AB  - We assessed the effect a sound-induced cochlear lesion had on the tonotopic
      organization of the nucleus magnocellularis (NM) immediately after acoustic
      overexposure and following a twelve day recovery period. The acoustic
      overexposure was a 0.9 kHz tone at 120 dB sound pressure level (SPL) for 48 h.
      Initially after the acoustic overexposure, the tonotopic organization of the NM
      was statistically different from that of age-matched controls. Specifically, it
      appeared that the center frequencies of units in the frequency region of the NM
      associated with the acoustic overexposure had higher center frequencies than
      their control counterparts. Following a twelve day recovery period, when
      threshold sensitivity and frequency selectivity were operating normally, the
      tonotopic organization of the NM was not statistically different from age-matched
      controls. We suggest that the sound-induced changes in the tonotopic organization
      of the NM reflect peripheral damage in the basilar papilla. It has been well
      documented that similar exposure paradigms produce a loss of short hair cells and
      a degeneration of the tectorial membrane in the region of the basilar membrane
      associated with the overexposure. We postulate that the loss of these structures
      alters the micromechanics and tuning of the basilar membrane which is reflected
      in the observed changes in NM tonotopy. Following the recovery period, when those
      structures destroyed by the overexposure had regenerated and basilar membrane
      micromechanics were operating normally, the tonotopic organization of the NM
      returned to normal.

PMID- 7737921
TI  - Responses of neurons in the ferret superior colliculus to the spatial location of
      tonal stimuli.
AB  - Using multi-unit recordings, we compared the azimuthal spatial selectivity of
      auditory neurons in the deep layers of the ferret superior colliculus (SC) to
      broadband and tonal stimuli. Responses to noise were tuned at different sound
      levels to a single location, which varied topographically along the rostrocaudal
      axis of the nucleus to form a map of sound azimuth. Frequency response profiles
      tended to be multi-peaked, so the spatial tuning was examined at two or more
      frequencies in each case. Some of the azimuthal response profiles obtained with
      tonal stimuli were bilobed, as expected from the spatially ambiguous cues
      available at individual frequencies, although the rest were tuned to a single
      region of space. The preferred sound directions usually varied with the frequency
      used, and the range of auditory best positions at each recording site was
      significantly greater with tones than with noise. Comparison with the acoustical
      properties of the auditory periphery suggested that the near-threshold positional
      selectivity of many of the tonal responses may be determined by the monaural
      directionality of the outer ear. When the sound level was raised by 20 dB so that
      both ears were stimulated at all speaker locations, the range of tonal best
      positions obtained at each frequency increased and some of the units responded
      best to pure tones located in the ipsilateral hemifield. The lack of topographic
      order in the distribution of tonal spatial selectivity along the rostrocaudal
      axis of the SC indicates the need for a broadband input, incorporating the
      spectral localization cues provided by the outer ear, in the construction of a
      neural map of auditory space.

PMID- 7737923
TI  - Shapes of cat auditory nerve fiber tuning curves.
AB  - Tuning curves of auditory nerve fibers in normal-hearing cats were fitted by a
      computational model comprising four processes. One process accounts for
      sensitivity in tuning curve tails and consists of an approximation to bandpass
      filtering by extracochlear structures. The second and third processes describe
      passive and active components of basilar membrane (BM) mechanics, respectively.
      The former consists of a lowpass filter function, which provides baseline
      threshold sensitivity and filtering above characteristic frequency (CF), and the
      latter consists of a Gaussian that accounts for sharp tuning and high sensitivity
      around CF. A fourth process, modeled as a high-pass filter, was needed in many
      fits to account for breaks and plateaus in threshold sensitivity at frequencies
      above CF. The latter three processes operated on cochlear spatial coordinates
      rather than stimulus frequency. The four-process description closely accounted
      for shapes of most tuning curves. Tuning curve tails possessed minima at 40-80 dB
      SPL, and minima increased with fiber CF. High-frequency cutoffs of tail filters
      tended to increase with CF, but low-frequency cutoffs were generally constant
      across CF. Functions describing tails varied from ear to ear but behaved in a
      similar manner for fibers from a single ear. Passive components of BM resonances
      possessed baselines with sensitivities that decreased with CF and cutoff slopes
      that increased with CF. The magnitude of the active component increased smoothly
      with CF over an 80 + dB range, and its spatial extent was essentially constant at
      1.5 mm or 6% of cochlear length regardless of gain magnitude, fiber CF, or
      threshold sensitivity. Tuning curves from fibers with high and medium spontaneous
      rates (SRs) and similar CFs had nearly identical shapes, with the sole difference
      being essentially constant differences in sensitivity across the entire
      excitatory frequency range. Tuning curve shapes from fibers with low SRs were
      more variable. These could either resemble those obtained from similarly-tuned
      fibers with higher SRs, or they could exhibit lower tip-to-tail ratios and
      reduced active component magnitudes. The latter were typically associated with
      low maximum discharge rates.

PMID- 7737922
TI  - Cochlear pathology following chronic electrical stimulation of the auditory
      nerve: II. Deafened kittens.
AB  - The present study examines the effects of long-term electrical stimulation of the
      auditory nerve on cochlear histopathology and spiral ganglion cell survival in
      young sensorineural deafened cats. Eight kittens were deafened using kanamycin
      and ethacrynic acid, and implanted with bipolar or monopolar scala tympani
      electrodes. Following recovery from surgery the animals were unilaterally
      stimulated using charge balanced biphasic current pulses for 450-1730 hours over
      implant periods of up to four months. Charge densities varied from 0.6-0.9
      microC.cm-2 geom. per phase for monopolar electrodes to 12-26 microC.cm-2 geom.
      per phase for the bipolar electrodes. Electrically-evoked auditory brainstem
      responses (EABRs) were periodically monitored during stimulation to confirm that
      the stimulus levels were above threshold, and to monitor any change in the
      response of the auditory nerve. Following completion of the stimulation program
      cochleae were prepared for histological examination. EABRs exhibited relatively
      stable thresholds for both stimulated and implanted, unstimulated control
      cochleae for the stimulus duration. While the growth in response amplitude as a
      function of stimulus current remained stable for the bipolar control and
      monopolar stimulated cochleae, the five cochleae chronically stimulated using
      bipolar electrodes exhibited a moderate to large increase in response amplitude.
      These increases were associated with a more widespread fibrous tissue response
      which may have altered the current distribution within these cochleae. Implanted
      control cochleae exhibited significantly less tissue response within the scala
      tympani. Importantly, we observed no statistically significant difference in the
      spiral ganglion cell density associated with chronic electrical stimulation when
      compared with unstimulated control cochleae. While the present study supports the
      safe application of cochlear implants in young profoundly deafened children, it
      does not corroborate previous studies that have reported electrical stimulation
      providing a trophic effect on degenerating auditory nerve fibres.

PMID- 7737924
TI  - Brainstem auditory evoked potentials characteristics in mice: the effect of
      genotype.
AB  - Brainstem auditory evoked potentials (BAEPs) elicited by sound clicks were
      recorded as a function of stimulus intensity in pentobarbital anesthetized
      C57BL/6J and BALB/c male mice, 2.5 months old. At high stimulus intensities the
      BAEPs of both strains consisted of 4 positive and 4 negative waves (labelled P1
      P4 and N1-N4, correspondingly). However, great interstrain differences were
      observed. BALB/c mice were characterized by higher thresholds, less amplitudes,
      beginning with P1 peak, longer latencies and steeper in slope latency-intensity
      profiles. The data suppose that by this age C57BL/6J mice have better auditory
      acuity, than BALB/c, and in BALB/c mice the pronounced abnormalities appear to
      arise in cochlear-auditory nerve system. Analysis of BAEPs using interpeak
      latencies (IPLs) and amplitude ratios intensities (ARs) profiles technique
      demonstrated no general trend that could fit for all IPLs as well as for all Ars
      changes by varying stimulus intensity. The obtained interstrain and interpeak
      differences in BAEPs parameters suggest that auditory information processing may
      vary greatly as a function of brainstem level.

PMID- 7737925
TI  - On the shape of (evoked) otoacoustic emission spectra.
AB  - In a preceding paper [Wit et al., (1994) Hear. Res. 73, 141-147] it was shown
      that realistic time-frequency plots for click evoked otoacoustic emissions can be
      synthesized by adding a large number of gammatones. It is necessary in such a
      synthesis to make the inner ear frequency to place map, from which the central
      frequencies of the gammatones are taken, slightly irregular along the entire
      cochlear partition. The present paper shows that this approach leads, in a rather
      straightforward way, to (quasi-) periodicity in synthesized spectra of evoked
      otoacoustic emissions. These spectra show good resemblance with spectra from real
      ear emission measurements.

PMID- 7737926
TI  - Anomalous cross-modal plasticity following posterior fossa surgery: some
      speculations on gaze-evoked tinnitus.
AB  - A unique and intriguing form of subjective tinnitus evoked by eye gaze is
      reviewed. A new perspective is presented because this condition is sufficiently
      different from other forms of subjective tinnitus and its manifestation cannot be
      adequately explained by existing models or conceptual frameworks. Our examination
      of this topic considers pathophysiologic changes in the central nervous system in
      the context of deafferentation-induced plasticity. Potential neuroanatomical
      areas contributing to this effect include a number of distributed and
      functionally diverse areas in the brainstem and neocortex involved in the
      auditory control of eye movements. We also consider contemporary psychophysical
      methods to evaluate the perceptual correlates of this phenomenon and tools for
      the development of objective tinnitus measurements. Although theoretical and
      speculative in nature, this article is intended to stimulate interest in, advance
      knowledge of, and provide a better understanding about this condition.

PMID- 7737927
TI  - Modulation of cyclic AMP production by strial marginal cells from gerbil in
      culture.
AB  - To further investigate the role of marginal cells (MCs) in the secretion of
      endolymph and because of the limitations encountered in investigating these cells
      in vivo, we used primary cultures of MCs derived from explants of gerbil stria
      vascularis and investigated modulation of the adenylate cyclase-cyclic AMP
      system. After 10 days on type I collagen coated plastic dishes, a confluent
      monolayer of epithelial-like cells was obtained which exhibited the morphologic
      and immunohistochemical features of the native marginal cells. The cyclic AMP
      (cAMP) content was determined at 37 degrees C, after 5 min of incubation with
      various agents, in the presence of a specific inhibitor of type III cAMP
      dependent phosphodiesterase, RO 20-1724. The adenylate cyclase-cAMP system was
      associated with beta 2-adrenergic receptors. The cAMP content was increased by
      isoproterenol (23-fold), a beta-agonist, but not by octopamine, an alpha-agonist,
      and the affinity for ICI 118.551, a specific beta 2-antagonist, was greater than
      for CGP 20712A, a specific beta 1-antagonist (Kd: 0.03 x 10(-6) M and 15 x 10(-6)
      M respectively). The cAMP content was maximally increased by prostaglandin E2 >
      beta 2-adrenergic agonist >> vasopressine type 2 receptor agonist (26-, 23-, and
      3-fold the basal cAMP content, respectively). The present study demonstrates that
      cultured marginal cells retain some of their in vivo properties including a
      modulated enzymatic cAMP system. This culture model should allow further in-depth
      investigation of the function of marginal cells.

PMID- 7737928
TI  - Distortion product otoacoustic emissions in an active nonlinear model of the
      cochlea.
AB  - An active nonlinear model of the cochlea in the form of a transmission line was
      presented, in which the active feedback system by outer hair cells (OHCs) was
      expressed as a series of low-pass filters on the basilar membrane (BM) which were
      transducing basilar membrane displacement to feedback force. The model could
      produce distortion product oto-acoustic emissions (DPOAEs) explicitly as well as
      sharp tuning curves of BM, and it was possible to discuss the cause of DPOAEs in
      terms of the active feedback. It was inferred that the nonlinearity of the
      cochlea which causes DPOAEs may be related to a saturating property of the
      feedback system by OHCs.

PMID- 7737930
TI  - Exposure to low frequency noise during rearing induces spongiform lesions in
      gerbil cochlear nucleus: high frequency exposure does not.
AB  - Spongiform lesions of the gerbil cochlear nucleus are reduced in number and
      extent by rearing in acoustic isolation compared with rearing while exposed to
      normal colony low-frequency background noise. This study tested whether rearing
      under exposure to noise bands of moderate intensity would increase the number and
      extent of cochlear nucleus spongiform lesions. Gerbils were reared from weaning
      to young adulthood in acoustic isolation chambers while continually exposed to
      moderately intense bands of either high frequency or low frequency noise.
      Exposure to low frequency noise resulted in lesion number and area densities that
      were more than twice those seen in gerbils exposed to high frequency noise.
      Lesion extent in the low frequency group was similar to that in colony-reared
      gerbils; lesion extent in the high frequency group was similar to gerbils reared
      in acoustic isolation. Comparisons within the posterior ventral cochlear nucleus
      revealed that the differences in lesion extent were most pronounced in the middle
      and dorsal-medial portions, the regions that are most responsive to middle and
      high frequencies. These finding suggest that the regional restriction of
      spongiform lesions within the cochlear nucleus does not have a tonotopic basis.

PMID- 7737929
TI  - Supranuclear efferent synapses on outer hair cells and Deiters' cells in the
      human organ of Corti.
AB  - Synaptophysin immunoreactivity and transmission electron microscopy have
      demonstrated vesiculated nerve endings synapsing on the supranuclear zone of
      outer hair cells and also of Deiters' cells in the human organ of Corti. These
      fibers seem similar to supranuclear fibers, apparently derived from the
      olivocochlear efferent system, which have been described in the animal. However,
      these endings were found throughout the cochlea in the human whereas in the
      animal such fibers were limited to the apical cochlea. Although such fibers have
      been demonstrated among supporting cells by immunohistochemical techniques, this
      is the first demonstration by transmission electron microscopy of morphology
      consistent with a chemical synapse between such fibers and Deiters' cells.
      Although the role of such fibers is unknown, neurophysiologic evidence suggests
      that they may modify the micromechanics of the outer hair cell. The function of
      neural innervation of Deiters' cells is speculative.

PMID- 7737931
TI  - Adaptation in the compound action potential response of the guinea pig VIIIth
      nerve to electric stimulation.
AB  - An experimental study, carried out in guinea pigs, was designed to investigate
      whether forward masking measured psychophysically in 3M-House cochlear implant
      users might have a correlate in VIIIth nerve activity. The study was based on
      electrically evoked VIIIth nerve compound action potentials (ECAPs), using a
      masking paradigm comparable to the one used in the psychophysical study. Trains
      of 50 maskers with inter-masker-intervals of 509 ms appeared to induce a long
      term fatigue effect that could influence the recovery from adaptation
      measurements. Fatigue stabilized within about 1 to 3 min when masker trains were
      repeated with intervening silent intervals of 10.5 s. The change in amplitude of
      probe-evoked ECAPs with increasing masker-probe delays was determined within the
      steady fatigue state. The recovery-from-adaptation functions obtained from these
      measurements resembled the forward masking functions found in 3M-House cochlear
      implant users. No correlate of psychophysical backward masking was found at the
      VIIIth nerve level. To examine whether hair cells were involved in fatigue and
      recovery from adaptation, the measurements described above were carried out in
      intact cochleas and in cochleas without hair cells. Results were essentially the
      same in the different preparations. The results suggest that processes at the
      level of the VIIIth nerve could, at least partly, account for forward masking
      found in 3M-House cochlear implant users. Backward masking must be attributed to
      mechanisms located centrally to the VIIIth nerve.

PMID- 7737932
TI  - Living isolated cells from inner ear vessels: a new approach for studying the
      regulation of cochlear microcirculation and vascular permeability.
AB  - The spiral modiolar artery with its proximal branches and the microvessels in the
      spiral ligament and the stria vascularis were microdissected from the guinea pig
      cochlea. After incubation with proteolytic and collagenolytic enzymes the mixed
      cell suspension was fractionated by gradient centrifugation. The cells migrated
      according to their buoyant densities into the fractions of 1.04 g/ml (endothelial
      cells), 1.06 g/ml (vascular smooth muscle cells obtained from the spiral modiolar
      artery; strial pericytes) and 1.08 g/ml (pericytes obtained from the spiral
      ligament). To test for viability cells were loaded with a fluorescent vital stain
      (BCECF-AM); for identification, cell-specific stains were used. Identity of
      endothelial cells (ECs) was confirmed using acetylated low density lipoprotein
      fluorescently labeled with dioctadecyl-tetramethyl-indocarbocyanine perchlorate
      (DiI-Ac-LDL). Pericytes were identified immunofluorescently using the method
      according to Nayak et al. (1988). Vascular smooth muscle cells were stained for F
      actin with rhodamin-phalloidin. This in vitro technique may open new approaches
      to study local factors involved in microcirculation and vessel permeability of
      various cochlear vascular beds.

PMID- 7737933
TI  - Human auditory cortical mechanisms of sound lateralisation: III. Monaural and
      binaural shift responses.
AB  - Neuromagnetic responses were recorded over the whole head with a 122-channel
      gradiometer. A pair of 150-ms 1-kHz tones separated by an interval of 150 ms was
      presented to one ear every 2 s. The other ear received either no input, an
      identical pair simultaneous to the first, an identical pair alternating with the
      first or a continuous 600-ms tone. The 'monaural shift' condition in which
      stimuli alternated between ears produced a clear perception of changing
      lateralisation, but the evoked response could be explained as merely the sum of
      simple monaural onset and offset responses; thus we found no evidence for a
      separate response to interaural intensity difference in this condition. The
      'binaural shift' condition, in which intensity changed in one ear while the other
      received a continuous tone, evoked a transient response (N130m) at a latency of
      about 130 ms. N130m was larger over the hemisphere contralateral to the direction
      of shift, and larger than the corresponding monaural response, whether to an
      onset or an offset. We concluded that N130m also was not a separate directional
      response, but was analogous to a simple monaural response, the prolonged latency
      being due to masking and the enhanced amplitude to facilitation by the sustained
      response to the continuous tone.

PMID- 7737934
TI  - Longitudinal field investigation of the moderating and mediating effects of self
      efficacy on the relationship between training and newcomer adjustment.
AB  - A longitudinal field study examined the moderating and mediating effects of self
      efficacy on the relationship between training and the adjustment of newcomers
      during their 1st year of employment. The results provided some support for the
      hypothesis that initial self-efficacy moderates the relationship between training
      and adjustment. Training was more strongly related to posttraining self-efficacy,
      ability to cope, job performance, and intention to quit the profession for
      newcomers with low levels of initial self-efficacy mediates the relationship
      between training and adjustment; however, evidence of complete mediation was
      found only for ability to cope. Posttraining self-efficacy partially mediated the
      relationships between training and job satisfaction, organizational and
      professional commitment, and intention to quit the organization and the
      profession. Research and practical implications of these findings for the
      training and the socialization of newcomers are discussed.

PMID- 7737935
TI  - Self-fulfilling prophecy and gender: can women be Pygmalion and galatea?
AB  - To date, all published confirmations of the Pygmalion hypothesis among adults
      have involved men. The few studies among women have had methodological
      ambiguities. The authors conducted 2 experiments in the Israel Defense Forces to
      test the Pygmalion hypothesis among women. In both studies, the leaders were led
      to believe that the trainees randomly assigned to the Pygmalion condition had
      higher than usual potential. Experiment 1 tested the Pygmalion hypothesis among
      female officer cadets led by women. Although the treatment did raise
      expectations, none of the performance measures and none of the mediators or the
      moderators evidenced any expectancy effects. Experiment 2 tested the Pygmalion
      hypothesis among women and men taking the same course in gender-segregated
      platoons. The Pygmalion hypothesis was confirmed among men led by a man and among
      women led by a man but not among women led by a woman. The authors concluded that
      the Pygmalion effect can be produced among women but perhaps not by women.
      Pygmalion research among women leading men is now needed.

PMID- 7737936
TI  - Collection and use of circulating hematopoietic progenitor cells.
AB  - Although lymphocytes and monocytes are becoming increasingly important in
      transfusion therapy, peripheral stem cells have been responsible for the recent
      explosive interest in harvesting mononuclear cells from the peripheral
      circulation. Despite their low concentration in peripheral blood and the
      consequent difficulty in cell collection, circulating hematopoietic progenitor
      cells are collected and used almost routinely. These mononuclear cells,
      possessing the capacity for hematopoietic reconstitution and the potential for
      definitive therapy of a variety of disorders, have been the focus of recent
      intense interest in transfusion medicine.

PMID- 7737937
TI  - Transfusion-transmitted retrovirus infection.
AB  - This article reviews the history, classification, and disease associations of the
      known human retroviruses and outlines their profound effects on the practice of
      transfusion medicine. The immunodeficiency viruses, HIV-1 and HIV-2, produce a
      cytolytic effect on infected lymphocytes, and are the causative agents of AIDS.
      In contrast are the oncoviruses, including HTLV-I and HTLV-II, which are
      typically lymphoproliferative and able to induce cellular transformation. Human
      foamy viruses, more recently recognized as a potential human neuropathogen,
      resemble the other retroviruses with their complex genome organization and
      structure.

PMID- 7737938
TI  - Transfusion-transmitted hepatitis virus infection.
AB  - For many years, viral hepatitis has been considered to be a frequent and serious
      adverse outcome of blood transfusion. The majority of cases have been due to
      hepatitis B and C viruses, which, respectively, are DNA and RNA viruses. Both are
      lipid enveloped and are susceptible to viral inactivation procedures. Careful
      donor screening and the use tests for HBsAg and anti-HBc have essentially
      eliminated the risk of transfusion-transmitted HBV infection.

PMID- 7737939
TI  - Transfusion-transmitted cytomegalovirus infection.
AB  - Transfusion-associated cytomegalovirus (CMV) infections is associated with
      significant morbidity and mortality in immunocompromised seronegative patients.
      Seronegative blood products reduce the incidence of infection to less than 7%.
      Filtered blood may be an effective alternative to seronegative blood products for
      prevention of transfusion-associated CMV infection. The clinical significance of
      second strain CMV infection remains undefined.

PMID- 7737940
TI  - Transfusion-transmitted bacterial infection.
AB  - Transfusion-transmitted bacterial infection is a persistent but often
      underemphasized problem facing transfusion medicine today. The present status of
      bacterial contamination of red cells, platelet products and plasma, frequency of
      contamination, and types of organisms implicated is reviewed. Current methods of
      prevention and detection are discussed, as well as typical clinical presentations
      and therapy.

PMID- 7737941
TI  - Noninfectious complications of blood transfusion.
AB  - The noninfectious complications of blood transfusion consist of a diverse group
      of immune-mediated transfusion reactions that range from immediate life
      threatening to subclinical reactions. Each reaction involves the recognition and
      interaction of the both the humoral and cellular immune systems. In the past,
      many of the noninfectious complications of transfusion were attributed solely to
      antigen-antibody interactions. Today, an emerging body of evidence suggests that
      cytokines and cytokine inhibitors play a central role in the pathophysiology of
      immune-mediated transfusion reactions and account for the broad diversity of
      clinical presentations.

PMID- 7737942
TI  - Immunosuppressive effects of allogeneic blood transfusions: implications for the
      patient with a malignancy.
AB  - A considerable amount of information has accumulated over the past decade
      indicating that the transfusion of allogeneic blood products may be associated
      with adverse effects to the recipient. These include the development of
      transfusion reactions, TA-GVHD, HLA-alloimmunization, and immunomodulatory
      effects. The latter might be beneficial for recipients of kidney allografts, in
      reducing the relapse rate in patients with Crohn's disease, and in ameliorating
      the rate of recurrence of spontaneous abortion in affected patients; however, the
      immunosuppressive effects associated with perioperative ABT might adversely
      affect overall prognosis in patients with a malignancy who undergo curative
      cancer surgery. In addition, ABT has been shown to be associated with an
      increased risk for postoperative bacterial infections. The ABT-induced
      immunomodulatory effects appear to be mediated immunologically by transfused
      allogeneic passenger leukocytes. The 3 log10 leukocyte reduction of cellular
      blood products, provided by the currently available commercial leukocyte filters,
      has been shown to minimize the occurrence of some of the ABT-associated
      deleterious effects; however, the actual clinical efficacy of leukodepletion has
      not yet been established, because the available data are largely from
      retrospective or uncontrolled clinical studies. Properly designed prospective
      clinical trials are essential to establish optimal conditions for the preparation
      of blood components destined for clinical use.

PMID- 7737943
TI  - Quality assessment and improvement of transfusion practices.
AB  - A successful quality assessment program simultaneously creates, sustains and
      documents excellence in patient care. As clinical practices evolve, it helps to
      assure their continuing improvement. The program strives to eliminate unnecessary
      transfusions as the cornerstone of transfusion safety. It should be conducted in
      a professional, nonadversarial, and educational manner.

PMID- 7737944
TI  - The role of hematopoietic growth factors in transfusion medicine.
AB  - Hematopoietic growth factors have already had an enormous impact on transfusion
      practice by eliminating or reducing the need for red blood cell transfusions in a
      variety of anemic states characterized by an absolute or relative decrease in
      erythropoietin. In addition, GM-CSF and G-CSF have stimulated the production of
      autologous neutrophils in febrile neutropenic patients in whom granulocyte
      transfusions had been considered ineffective. With the discovery of c-Mpl ligand
      and the promising results obtained with IL-11 and IL-3, a combination of growth
      factors that successfully stimulate platelet production may soon be identified.
      This first era in the clinical application of hematopoietic growth factors has
      been characterized largely by treatment of the patient to stimulate production of
      autologous cells or to enhance the ability of transplanted hematopoietic
      progenitor cells to repopulate the patient. The use of G-CSF to increase the
      yield of granulocytes harvested by apheresis procedures and to mobilize
      peripheral blood stem cells in allogeneic donors has initiated a new era in which
      the cell donor is treated to enhance cell production and enhance the repopulating
      ability of hematopoietic progenitor cells. As our understanding of hematopoiesis
      grows, scientists will be able to identify growth factors to overcome or correct
      deficient hematopoiesis. Increasingly, component transfusions will be reserved
      for life-threatening situations in which endogenous cell production cannot be
      stimulated or cell production will be too slow to prevent life-threatening
      events.

PMID- 7737945
TI  - The use of leukocyte-reduced blood components.
AB  - Many of the risks and discomforts associated with blood transfusion may be
      avoided by removing the contaminating leukocytes from cellular blood components.
      Leukocyte reduction prevents many febrile reactions that occasionally occur
      following red cell transfusion and prevents some febrile reactions following
      platelet transfusion. Prophylactic use of leukocyte-reduced components may
      prevent primary HLA alloimmunization, which is a principle cause of the
      refractoriness to platelet transfusion seen in many multiply transfused,
      thrombocytopenic patients. Leukocyte-reduced components are equally effective in
      the prevention of CMV as seronegative blood.

PMID- 7737946
TI  - Cellular gene therapy.
AB  - During the last decade, molecular genetic techniques have been used increasingly
      to transfer human genes into mammalian cells, to correct and enhance cell
      function, and finally to treat human disease. Despite the current obstacles to
      developing even the simplest therapeutic strategy, gene therapy promises to have
      an almost unlimited future. The ability to collect specific blood cells in large
      numbers, to manipulate their expansion, growth, and differentiation in vitro, and
      also to cryopreserve these cells for later use has been central to the early
      developments in gene therapy. This article reviews the major concepts involved in
      blood cell-based gene therapy, a model for all somatic cell gene therapy.

PMID- 7737947
TI  - "Press [2] to dictate....".
AB  - Why do so few people understand what a medical transcriptionist really does?
      Because medical transcription, which is frequently performed in a home office or
      remote location, is an extremely solitary profession which relies on highly
      specialized language and interpretive skills. Many doctors still think of MTs as
      "those ladies in the basement of the hospital who sit there typing all day." But
      with hospitals farming out the bulk of their dictation to transcription agencies
      in a desperate attempt to cut back on benefitted employees, a physician's words
      may be transcribed hundreds or thousands of miles from the patient's bed. Back in
      medical school--when you were filled with dreams of healing the sick--no one ever
      told you about the endless hours you would spend dictating patient reports and
      dealing with mountains of paperwork. The hard truth is that most physicians are
      drowning in paperwork as third-party insurers continue to demand increased
      documentation before authorizing payment. The demands for increased documentation
      are not going to go away. Nor is the pile of charts sitting in front of you. So,
      even though you're exhausted, you sit down and begin to dictate. How do your
      words end up in print? They pass through the mind of a language specialist who
      makes what you said look a lot better than what you really said.

PMID- 7737948
TI  - Refractive surgery.

PMID- 7737949
TI  - Facts and stats on tobacco and smoking.

PMID- 7737950
TI  - The chest X-ray in the diagnosis of acute pulmonary embolism: Westermark's sign.

PMID- 7737951
TI  - Radiological case of the month. Lymphoma.

PMID- 7737953
TI  - Arkansas HIV/AIDS report 1983-1995.

PMID- 7737952
TI  - VANQWISH: risk stratification of non Q-wave myocardial infarction.

PMID- 7737954
TI  - Radiological case of the month. Intradural lipoma.

PMID- 7737955
TI  - Medication use during psychoanalysis: a survey.
AB  - BACKGROUND: Historically, the psychoanalytic community has rejected the use of
      psychotropic medication, on the basis of the belief that using medication to
      suppress symptoms such as depression and anxiety would obstruct access to psychic
      conflict and thereby impede the progress of analytic treatment. However, it would
      appear that many psychoanalysis have reconsidered this point of view and are now
      combining medication with psychoanalytic treatment. This paper reports the first
      systematic survey of medication use in psychoanalysis. METHOD: Forty-five
      training analysts at the Columbia University Center for Psychoanalytic Training
      and Research were sent questionnaires that asked how many patients in analysis
      they had seen in the past 5 years and for details about any of those patients who
      had taken psychotropic medication. RESULTS: The analysts reported that in the
      past 5 years, 51 (18%) of 277 patients in analysis were also taking psychotropic
      medication. Most of these patients had been diagnosed with a unipolar mood
      disorder and were treated with some type of antidepressant. In 84% of patients
      (36 of 43) with a unipolar mood disorder who had been treated with medication,
      the psychoanalyst judged that both the mood disorder and the analytic process
      improved. CONCLUSION: The use of medication in combination with psychoanalysis is
      no longer an uncommon practice. Analysts who prescribe medication find that, in
      general, the effect is to enhance rather than undermine the psychoanalytic
      process.

PMID- 7737956
TI  - Efficacy and adverse effects of clozapine in four elderly psychotic patients.
AB  - BACKGROUND: Clozapine is an atypical antipsychotic agent that is effective in
      refractory schizophrenic patients. Older patients may have various psychotic
      manifestations that may not be responsive to typical neuroleptic therapy. There
      may also be patient-specific factors--declines in reserve capacity and
      homeostasis, and age-related changes in the pharmacokinetics and pharmacodynamics
      of drugs--in older patients that increase their susceptibility to the side
      effects of psychotropic medications. While clozapine has few extrapyramidal side
      effects, it has other side effects that may be problematic in the older
      population. METHOD: In our geropsychiatric unit, clozapine was prescribed for
      four patients over the age of 65 years. All patients were either experiencing
      psychotic symptoms refractory to other antipsychotic medications or had relative
      contraindications to a typical neuroleptic. Two of the four were chronic
      schizophrenics, and three of the four also presented with dementia. RESULTS: Two
      of the four patients did eventually receive relief of psychotic symptoms from
      clozapine. All four experienced events after initiation of clozapine therapy,
      which included falls (2 patients), symptomatic bradycardia (2 patients), and
      delirium (1 patient). All these adverse effects occurred on doses ranging from
      6.25 to 37.50 mg/day, and the three patients with moderate-to-severe dementia
      experienced these severe adverse effects after administration of the first dose.
      CONCLUSION: Clozapine may be a useful drug for older patients with psychotic
      symptoms; however, at current dosage recommendations, adverse events may occur,
      especially on first dose. Well-designed studies need to be performed to assess
      the effectiveness and dosage ranges for this population.

PMID- 7737957
TI  - Hypothyroidism and hyperthyroidism in major depression revisited.
AB  - BACKGROUND: The aim of our study was to evaluate the prevalence of thyroid
      abnormalities among depressed outpatients and to examine the response to
      treatment of those subjects with relatively low or high thyroid hormone levels.
      METHOD: Outpatients (N = 200) 18 to 65 years of age who met DSM-III-R criteria
      for major depression were screened for the presence of thyroid abnormalities
      using a number of thyroid indices. Of these patients, 166 were then treated
      openly with the antidepressant fluoxetine for 12 weeks. We assessed whether
      patients with relatively low or high thyroid hormone levels had a different
      response to treatment compared with other patients. The 17-item Hamilton Rating
      Scale for Depression (HAM-D-17) was administered during the study to assess
      changes in depressive symptoms. Thyroid function was assessed by measuring T3,
      T4, free T4 index (FT4I), T3 uptake (T3U), and serum thyroid-stimulating hormone
      (TSH) levels. RESULTS: No clinical cases of hyperthyroidism or hypothyroidism
      were detected. Of the patients examined, 5 (2.6%) had slightly elevated TSH
      levels (range, 4.7-8.2); none of these had T4 or FT4I levels below the normal
      range. Subnormal levels of T4 or FT4I were found in 1 subject (0.5%). T3 and T3U
      levels were below the normal range in a larger number of patients (7.6% and 15.0%
      respectively), but only 1 of these patients had elevated TSH levels. None of the
      patients had levels of TSH below the normal range, and only 3 subjects (1.5%) had
      T4 levels above the normal range. No relationship was found between response rate
      (assessed as either change in HAM-D-17 score or as remission of depressive
      symptoms with a HAM-D-17 score < or = 7 for 3 consecutive weeks) and each of the
      thyroid tests, even after adjusting for baseline severity of depression.
      CONCLUSION: In depressed outpatients, it appears that hypothyroidism and
      hyperthyroidism are extremely uncommon and that the presence of subtle thyroid
      function abnormalities does not have an impact on treatment outcome.

PMID- 7737958
TI  - A further prospective evaluation of an equation to predict daily lithium dose.
AB  - BACKGROUND: Recently, one prospective study confirmed the safety and accuracy of
      a lithium-dose prediction equation created by Zetin et al., but no definitive
      conclusion on the reliability of the equation has been established as yet.
      METHOD: The authors applied the Zetin et al. equation to 18 chronic male
      schizophrenic inpatients. Predicted doses to reach the serum lithium
      concentration of 0.4 mmol/L were calculated and prescribed in the form of lithium
      capsules. At Weeks 1 and 3 after treatment initiation, morning blood samples were
      collected about 12 hours after the last lithium dose for the measurement of serum
      lithium concentrations. RESULTS: None of the 18 patients achieved the desired
      concentration (0.4 mmol/L) exactly. The mean +/- SD of serum lithium
      concentrations at Week 1 was 1.01 +/- 0.29 mmol/L (range, 0.2-1.5) and at Week 3
      was 0.94 +/- 0.35 mmol/L (range, 0.2-1.8). Lithium concentrations were lower than
      0.4 mmol/L in only 1 patient and were higher than 0.4 mmol/L in the other 17
      patients. The deviations from the unexpected value were significantly correlated
      with the renal function (blood urea nitrogen and serum creatinine levels) but not
      with the neuroleptic doses administered to the patients. Moreover, our patients
      were relatively older and weighed relatively less than the patients described in
      the previous prospective study. CONCLUSION: The Zetin et al. equation cannot
      always accurately predict a required lithium dose. Renal function data, even when
      they range within normal values, may be useful to improve the accuracy of the
      equation, particularly in patients who are older or weigh less than the norm.

PMID- 7737959
TI  - Monoamine oxidase inhibitor dietary restrictions: what are we asking patients to
      give up?
AB  - BACKGROUND: Though the list of possible indications for monoamine oxidase
      inhibitors (MAOIs) continues to expand, many psychiatrists remain hesitant about
      prescribing MAOIs, citing concerns about dietary prohibitions and hypertensive
      reactions. Data about psychiatric patients' frequency of consumption of foods,
      beverages, and medications prohibited during MAOI use are lacking. METHOD: We
      conducted a survey of 139 psychiatric patients admitted to either an inpatient
      unit specializing in the treatment of mood disorders or an outpatient anxiety
      disorders clinic specializing in the treatment of social phobia. At inclusion,
      patients were not being treated with MAOIs, although they might have received
      such treatment afterward. All patients completed a self-report questionnaire
      created for this study to ascertain their consumption of food, beverage, and
      medication items frequently found on MAOI diet lists. Demographic and diagnostic
      information was also recorded. RESULTS: The most frequently used high-risk items
      were the hard cheeses. Ninety percent of patients reported daily or weekly
      consumption of some food containing cheese, while less than 1% of patients
      reported never eating hard cheese. Yeast products, dry sausage, corned beef,
      broad beans, sauerkraut, and beer were used at least monthly by more than 50% of
      patients. Of the intermediate-risk foods, chocolate was the most frequently
      consumed, with almost 30% of the patients eating some chocolate daily. Over 40%
      of patients reported using over-the-counter cold preparations on a monthly basis.
      CONCLUSION: A wide variety of tyramine-containing foods and contraindicated
      medications were commonly used by our patients prior to evaluation for possible
      MAOI pharmacotherapy. The number and diversity of frequently consumed items do
      not support recommendations to reduce the breadth of restrictions in MAOI diets.
      Individually targeted dietary assessment and education are recommended to reduce
      the risks of prescribing MAOIs.

PMID- 7737961
TI  - Trichotillomania, body dysmorphic disorder, and obsessive-compulsive disorder.

PMID- 7737960
TI  - Adinazolam-SR in panic disorder with agoraphobia: relationship of daily dose to
      efficacy.
AB  - BACKGROUND: We report the results from a multicenter, double-blind, randomized,
      fixed-dose study designed to evaluate the relationship between daily dose and
      efficacy of adinazolam-SR in patients with panic disorder with agoraphobia.
      METHOD: Patients (N = 315) were randomized to one of four treatment groups
      (placebo, N = 83; 30-mg group, N = 79; 60-mg group, N = 81; and 90-mg group, N =
      72) and then treated twice daily for 4 weeks. All treatment groups were
      comparable demographically. Primary efficacy measures included total number of
      panic attacks, global improvement score using the Clinical Global Impressions
      (CGI) scale, phobic anxiety dimension of the Symptom Checklist-90 phobic cluster,
      overall phobia state using the Phobia Scale, and severity of illness on the CGI.
      RESULTS: The 60- and 90-mg/day adinazolam-SR treatment groups showed superior
      results when compared with the placebo group at Week 4 while the 30-mg group did
      not. Treatment with adinazolam-SR was well tolerated, with sedation the only
      treatment-emergent symptom that occurred more frequently in patients treated with
      adinazolam-SR than placebo. CONCLUSION: These results suggest that adinazolam-SR
      at doses of 60-mg/day or greater administered twice daily is a safe and effective
      treatment in selected patients with panic disorder with agoraphobia.

PMID- 7737962
TI  - Rabbit syndrome and tardive dyskinesia: two complications of chronic neuroleptic
      treatment.

PMID- 7737964
TI  - Post-transcriptional regulation of transposition by Ty retrotransposons of
      Saccharomyces cerevisiae.

PMID- 7737963
TI  - Current concepts in schizophrenia: international symposia report new standards
      for assessment and treatment. Part I: Pathophysiology research prompts assessment
      updates.

PMID- 7737965
TI  - Laminin SIKVAV peptide induction of monocyte/macrophage prostaglandin E2 and
      matrix metalloproteinases.
AB  - The laminin-derived synthetic peptide containing the SIKVAV (Ser-Ile-Lys-Val-Ala
      Val) amino acid sequence has been previously shown to regulate tumor invasion,
      metastasis, and angiogenesis. Here, we demonstrate that this peptide also
      modulates human monocyte responses. Moreover, the monocytic responses elicited by
      this peptide are influenced by the culture conditions. When elutriated monocytes
      were cultured on SIKVAV substrate or in suspension with this peptide, the
      synthesis of prostaglandin E2, interstitial collagenase, and gelatinase B was
      induced and was further enhanced in the presence of concanavalin A (ConA).
      However, when monocytes were adhered before adding soluble SIKVAV, the peptide
      alone failed to induce the production of prostaglandin E2 or matrix
      metalloproteinases. If adherent monocytes were exposed to SIKVAV in the presence
      of ConA, this peptide enhanced the ConA induced production of these mediators. In
      contrast to SIKVAV, the intact laminin molecule failed to influence these
      monocyte responses. This is the first demonstration that a laminin derived
      peptide is capable of inducing or enhancing monocyte inflammatory responses that
      may influence a number of biological activities such as wound healing or
      excessive connective tissue destruction associated with chronic inflammation.

PMID- 7737966
TI  - Sodium salicylate and yeast heat shock gene transcription.
AB  - The anti-inflammatory drug sodium salicylate modulates the activity of specific
      transcription factors in humans. Here we show that salicylate and sorbate,
      another organic acid, stimulate DNA binding by yeast heat shock transcription
      factor (HSF) in vivo. Surprisingly, salicylate inhibits heat shock gene
      transcription even in cells induced by a prior heat shock. This inhibition of
      transcription occurs at a step after HSF and transcription factor IID binding but
      before promoter melting by RNA polymerase. Salicylate appears to generate a tight
      binding but activation-impotent HSF by cytoplasmic acidification, since
      inhibiting proton efflux from cells triggers this same DNA binding and inhibition
      of heat shock gene expression.

PMID- 7737967
TI  - Cyclic AMP-dependent activation of Rap1b.
AB  - Rap1 proteins belong to the Ras superfamily of small molecular weight GTP-binding
      proteins. Although Rap1 and Ras share approximately 50% overall amino acid
      sequence identity, the effector domains of the two proteins are identical,
      suggesting either similar or antagonistic signaling roles. Several pathways
      leading to Ras activation have been defined, including those initiated by agonist
      binding to tyrosine kinase or Gi-coupled receptors. Nothing is known about such
      events for Rap1 proteins. The cAMP-mediated inhibition of Ras-dependent MAP
      kinase activation is well documented and resembles that caused by expression of
      GTPase-deficient Rap1. We have developed a system whereby signals leading to
      Rap1b activation, i.e. an increase in Rap1b-bound GTP/GDP ratio, can be measured.
      We report here that treatment of cells with agents that elevate intracellular
      cAMP levels result in Rap1b activation. These results demonstrate for the first
      time agonist-dependent activation of Rap1 proteins.

PMID- 7737968
TI  - Granzyme B is inhibited by the cowpox virus serpin cytokine response modifier A.
AB  - The ability of cytolytic cells to cause apoptosis in target cells is in part due
      to the action of the serine proteinase granzyme B. We demonstrate that granzyme B
      is inhibited, with an association rate constant of 2.9 x 10(5) M-1 s-1, by the
      cowpox viral serpin cytokine response modifier A (CrmA). Previously we have shown
      CrmA to be an inhibitor of the cysteine proteinase interleukin-1 beta-converting
      enzyme (ICE). Thus the mechanism of CrmA involves the unusual ability to
      efficiently inhibit proteinases from two distinct catalytic classes, in this case
      serine and cysteine proteinases. Granzyme B and ICE are both used to combat viral
      infection, and we propose that cowpox virus uses CrmA to evade the contribution
      of these two proteinases. Thus, through CrmA, the virus may influence two of the
      pathways normally used to kill virus-infected cells: acting on endogenous
      proteinases such as ICE and on exogenous proteinases delivered by cytotoxic
      lymphocytes to infected cells.

PMID- 7737969
TI  - Monocyte colony-stimulating factor stimulates binding of phosphatidylinositol 3
      kinase to Grb2.Sos complexes in human monocytes.
AB  - Monocyte colony-stimulating factor (M-CSF) is required for the proliferation of
      mononuclear phagocytes. The activated M-CSF receptor associates with
      phosphatidylinositol 3-kinase (PI 3-kinase). In the present studies, we
      demonstrate that M-CSF also induces direct interaction of PI 3-kinase (p85 alpha
      subunit) with the SH2/SH3 adaptor protein Grb2. Tyrosine-phosphorylated PI 3
      kinase interacts with the SH2 domain of Grb2. A pYRNE (pY408) site in PI 3-kinase
      is potentially involved in this interaction. The results also demonstrate that
      the PI 3-kinase.Grb2 complex associates with the guanine nucleotide exchange
      protein Sos. Since Sos binds to the SH3 domains of Grb2 and thereby associates
      with Ras at the cell membrane, formation of the PI 3-kinase.Grb2.Sos complex
      provides a potential mechanism for growth factor-induced interactions of PI 3
      kinase and Ras.

PMID- 7737970
TI  - The chondroitin sulfate attachment site of appican is formed by splicing out exon
      15 of the amyloid precursor gene.
AB  - Appicans are secreted and cell-associated chondroitin sulfate proteoglycans
      containing Alzheimer amyloid precursor (APP) as their core protein. Appicans are
      found in brain tissue, and in cell cultures their expression depends on both cell
      type and growth conditions. Here we report that the core protein of appicans
      derives from an APP mRNA lacking exon 15. Splicing out of this exon creates a new
      consensus sequence for the attachment of a chondroitin sulfate chain in the
      resulting APP product. Transfection of C6 glioma or 293 kidney fibroblast cells
      with APP cDNAs containing exon 15 produced no appican, while transfection with an
      APP cDNA lacking this exon induced high levels of appican production. Polymerase
      chain reactions indicated that appican-producing cells contained an APP mRNA
      species without exon 15, whereas cells without this mRNA produced no appican.
      Site-directed mutagenesis combined with immunoreactivity experiments showed that
      the chondroitin sulfate chain is attached to a serine residue 16 amino acids
      upstream of the amino terminus of the A beta sequence of APP. The attachment of a
      glycosaminoglycan chain close to the A beta sequence of APP may affect the
      proteolytic processing of APP and production of A beta. The proteoglycan nature
      of APP suggests that addition of the chondroitin sulfate glycosaminoglycan is
      important for the implementation of the biological function of these proteins.

PMID- 7737971
TI  - Ca(2+)-dependent binding of human serum amyloid P component to Alzheimer's beta
      amyloid peptide.
AB  - Serum amyloid P component (SAP), a normal glycoprotein, is universally found in
      amyloid deposits, including cerebrovascular amyloid of Alzheimer's disease. This
      paper describes the Ca(2+)-dependent binding of human SAP to Alzheimer's beta
      amyloid peptide (A beta). 125I-SAP binds to synthetic human A beta-(1-40)
      immobilized on microtiter plates at a dissociation constant of 6.0 x 10(-9) M in
      0.01 M Tris-HCl, 0.15 M NaCl, pH 7.5, containing 2 mM Ca2+, 1% bovine serum
      albumin, and 0.05% Tween 20. Binding inhibition assay has shown that soluble A
      beta-(1-40) and A beta-(1-28) also bind to SAP. Since SAP is resistant to
      proteases in the presence of calcium, the Ca(2+)-dependent binding of SAP to
      soluble A beta and to beta-amyloid fibrils would give pathological effects on
      fibril formation and persistence of beta-amyloid in Alzheimer's disease.

PMID- 7737972
TI  - Cloning and disruption of CKB1, the gene encoding the 38-kDa beta subunit of
      Saccharomyces cerevisiae casein kinase II (CKII). Deletion of CKII regulatory
      subunits elicits a salt-sensitive phenotype.
AB  - Saccharomyces cerevisiae casein kinase II (CKII) contains two distinct catalytic
      (alpha and alpha') and regulatory (beta and beta') subunits. We report here the
      isolation and disruption of the gene, CKB1, encoding the 38-kDa beta subunit. The
      predicted Ckb1 sequence includes the N-terminal autophosphorylation site,
      internal acidic domain, and potential metal binding motif (CPX3C-X22-CPXC)
      present in other beta subunits but is unique in that it contains two additional
      autophosphorylation sites as well as a 30-amino-acid acidic insert. CKB1 is
      located on the left arm of chromosome VII, approximately 33 kilobases from the
      centromere and does not correspond to any previously characterized genetic locus.
      Haploid and diploid strains lacking either or both beta subunit genes are viable,
      demonstrating that the regulatory subunit of CKII is dispensable in S.
      cerevisiae. Such strains exhibit wild type behavior with regard to growth on both
      fermentable and nonfermentable carbon sources, mating, sporulation, spore
      germination, and resistance to heatshock and nitrogen starvation, but are salt
      sensitive. Salt sensitivity is specific for NaCl and LiCl and is not observed
      with KCl or agents which increase osmotic pressure alone. These data suggest a
      role for CKII in ion homeostasis in S. cerevisiae.

PMID- 7737974
TI  - The dissociation of ATP from hsp70 of Saccharomyces cerevisiae is stimulated by
      both Ydj1p and peptide substrates.
AB  - hsp70 proteins of both eukaryotes and prokaryotes possess both ATPase and peptide
      binding activities. These two activities are crucial for the chaperone activity
      of hsp70 proteins. The activity of DnaK, the primary hsp70 of Escherichia coli,
      is modulated by the GrpE and DnaJ proteins. In the yeast Saccharomyces
      cerevisiae, the predominant cytosolic hsp70, Ssa1p, interacts with a DnaJ
      homologue, Ydj1p. In order to better understand the function of the Ssa1p/Ydj1p
      chaperone, the effects of polypeptide substrates and Ydj1p on Ssa1p ATPase
      activity were assessed using a combination of steady-state kinetic analysis and
      single turnover substrate hydrolysis experiments. Polypeptide substrates and
      Ydj1p both serve to stimulate ATPase activity of Ssa1p. The two types of effector
      are biochemically distinct, each conferring a characteristic K+ dependence on
      Ssa1p ATPase activity. However, in single turnover ATP hydrolysis experiments,
      both polypeptide substrates and Ydj1p destabilized the ATP.Ssa1p complex through
      a combination of accelerated hydrolysis of bound ATP and accelerated release of
      ATP from Ssa1p. The acceleration of ATP release by Ydj1p is a previously
      unidentified function of a DnaJ homologue. In the case of Ydj1p-stimulated Ssa1p,
      steady-state ATPase activity is increased less than 2-fold at physiological K+
      concentrations, despite a 15-fold increase in the hydrolysis of bound ATP. The
      primary effect of Ydj1p appears to be to disfavor an ATP form of Ssa1p. On the
      other hand, peptide stimulation of Ssa1p ATPase activity was enhanced at
      physiological K+ concentrations, supporting the idea that cycles of ATP
      hydrolysis play an important role in the interaction of hsp70 with polypeptide
      substrates. The enhanced ATP dissociation caused by both polypeptide substrates
      and Ydj1p may play a role in the regulation of Ssa1p chaperone activity by
      altering the relative abundance of ATP-and ADP-bound forms.

PMID- 7737973
TI  - Histidine 289 is essential for hydrolysis of the alkyl-enzyme intermediate of
      haloalkane dehalogenase.
AB  - Haloalkane dehalogenase (DhlA) from Xanthobacter autotrophicus GJ10 catalyzes the
      hydrolytic cleavage of carbon-halogen bonds in a broad range of halogenated
      aliphatic compounds. Previous work has shown that Asp124, which is located close
      to the internal substrate-binding cavity, carries out a nucleophilic attack on
      the C-alpha of the alkylhalide, displacing the halogen. The resulting alkyl
      enzyme intermediate is subsequently hydrolyzed. In order to study the role of
      His289 in the hydrolysis of the intermediate, a His289-->Gln mutant was
      constructed by site-directed mutagenesis. The purified mutant enzyme was not
      catalytically active with haloalkanes, but a halide burst stoichiometric to the
      amount of enzyme was observed with 1,2-dibromoethane. Using ion spray mass
      spectrometry, accumulation of the covalent alkyl-enzyme and binding of the alkyl
      moiety of the substrate to an Asp124-containing tryptic peptide were shown.
      Fluorescence-quenching experiments indicated that halide ions are strongly bound
      by the alkyl-enzyme but not by the substrate-free enzyme. The results show that
      His289 is the base catalyst for the dealkylation of the covalent intermediate,
      but that it is not essential for the initial nucleophilic attack of Asp124 on the
      C-1 atom of the haloalkane. Furthermore, the halide ion that is released in the
      first step probably leaves the active site only after hydrolysis of the alkyl
      enzyme.

PMID- 7737975
TI  - Specific activation of the Na+/H+ exchanger gene during neuronal differentiation
      of embryonal carcinoma cells.
AB  - We examined the regulation of the Na+/H+ exchanger gene during differentiation of
      the P19 mouse embryonal carcinoma cells. Treatment of P19 cells with retinoic
      acid induces the development of neurons, astroglia, and microglia cells. Upon
      retinoic acid-induced differentiation of P19 cells, there was an early and rapid
      10-fold increase in NHE1 transcription. A proximal cis-acting AP-2 site of the
      NHE1 promoter was sufficient for stimulation of transcription of the gene by
      differentiation. Bandshift experiments demonstrated that in retinoic acid-treated
      cells there was an elevated level of AP-2 transcription factor binding to the AP
      2 consensus site of the Na+/H+ exchanger gene. In the differentiation defective
      mutant RAC65, the effect of differentiation on Na+/H+ exchanger gene expression
      was reduced by 60%. Examination of Na+/H+ exchanger activity showed that retinoic
      acid-treated P19 cells recovered from an acid load at a rate approximately three
      times greater than untreated cells. The increases in gene expression and protein
      activity preceded major changes in cell morphology, suggesting that the
      initiation of differentiation is linked to NHE1 gene expression. Our findings
      show for the first time that the NHE1 gene is activated early in cell
      differentiation and that this activation may play an important role in the
      process of neuronal cell differentiation.

PMID- 7737977
TI  - Structure and in vitro molecular chaperone activity of cytosolic small heat shock
      proteins from pea.
AB  - Plants synthesize several classes of small heat shock proteins ranging in size
      from 15 to 30 kDa. Two conserved classes, designated class I and class II, are
      localized to the cytosol. Recombinant HSP18.1 and HSP17.7, representing class I
      and class II proteins from pea, respectively, were expressed in Escherichia coli
      and purified. Non-denaturing polyacrylamide gel electrophoresis and electron
      microscopy demonstrated that the purified proteins formed discretely sized, high
      molecular weight complexes. Sedimentation equilibrium analytical
      ultracentrifugation revealed that the HSP18.1 and HSP17.7 complexes were composed
      of approximately 12 subunits. Both proteins were able to enhance the refolding of
      chemically denatured citrate synthase and lactate dehydrogenase at stoichiometric
      levels in an ATP-independent manner. Furthermore, HSP18.1 and HSP17.7 prevented
      aggregation of citrate synthase at 45 degrees C and irreversible inactivation of
      citrate synthase at 38 degrees C. HSP18.1 also suppressed aggregation of lactate
      dehydrogenase at 55 degrees C. These findings demonstrate that HSP18.1 and
      HSP17.7 can function as molecular chaperones in vitro.

PMID- 7737976
TI  - The role of Tyr13 and Lys15 of interleukin-8 in the high affinity interaction
      with the interleukin-8 receptor type A.
AB  - Interleukin-8 (IL-8) has at least two binding regions for both the A and the B
      type IL-8 receptors. This study defines an important region between Cys7 and
      Cys50 that, together with the Glu4-Leu5-Arg6 sequence of the NH2 terminus,
      accounts for the high affinity binding of IL-8 to the IL-8 A receptor on
      leukocytes. Utilizing rabbit IL-8 that shares 82% sequence identity with human IL
      8, but has 200-fold lower binding affinity for the IL-8 A receptor, residues of
      the human homologue were sequentially exchanged into the rabbit molecule.
      Replacement of rabbit His13 and Thr15 with Tyr13 and Lys15 of the human molecule
      converted the low affinity binding of the rabbit IL-8 to the high affinity
      binding of human IL-8 as shown by both competitive binding and by Ca2+
      mobilization. As a corollary, replacement of the Tyr13 and Lys15 of the human IL
      8 with His13 and Thr15 of the rabbit IL-8 reduced binding activity of this
      mutated human IL-8 200-fold. The site of interaction on the IL-8 receptor type A
      for the Tyr13 and Lys15 sequence was found to be in the NH2-terminal region of
      this receptor. A structural pattern of the binding between IL-8 and the A type IL
      8 receptor is proposed.

PMID- 7737979
TI  - Resonance Raman investigation of cyanide ligated beef liver and Aspergillus niger
      catalases.
AB  - Resonance Raman spectroscopy has been used to investigate the properties of
      cyanide-bound beef liver catalase (BLC) and Aspergillus niger catalase (ANC) in
      the pH range 4.9-11.5. Evidence has been obtained for the binding of cyanide to
      both BLC and ANC in two binding geometries. The first conformer, exhibiting the
      nu[Fe-CN] stretching mode at a higher frequency than the delta[Fe-C-N] bending
      mode, exists as an essentially linear Fe-C-N linkage. For both BLC-CN and ANC-CN,
      the nu[Fe-CN] and delta[Fe-C-N] frequencies of this conformer were practically
      identical and observed at approximately 434 and approximately 413 cm-1,
      respectively. The second conformer exhibits a nu[Fe-CN] mode at lower frequency
      than the delta[Fe-C-N] mode, and is thus characteristic of a bent Fe-C-N linkage.
      The nu[Fe-CN] and delta[Fe-C-N] modes were identified at 349 and 445 cm-1,
      respectively, for BLC-CN, and at 350 and 456 cm-1, respectively, for ANC-CN. The
      two conformers persist in the pH range 4.9-11.5. Furthermore, upon raising the pH
      to 11.5, the nu[Fe-CN] mode of the linear conformer of BLC-CN downshifts to 429
      cm-1 while that of the bent conformer remains unchanged. The observed pH
      dependent shift is attributed to the deprotonation of a distal-side amino acid
      residue, probably a distal histidine. The Fe-C-N axial vibrations of the two
      conformers identified for ANC-CN did not show any significant pH-dependent
      shifts, indicating a more stable hydrogen bonding interaction relative to BLC-CN.

PMID- 7737978
TI  - Activation of protein kinase C enhances the phosphorylation of the type B
      interleukin-8 receptor and stimulates its degradation in non-hematopoietic cells.
AB  - We have previously characterized the stably transfected, clonally selected human
      placental cell line, 3ASubE P-3, which overexpresses the type B interleukin-8
      receptor (IL-8RB) and responds to the chemokine melanoma growth stimulatory
      activity (MGSA) with enhanced phosphorylation of this receptor. In work described
      here, we demonstrate that the MGSA-enhanced phosphorylation of this receptor is
      mediated via a process involving pertussis toxin-sensitive G proteins.
      Furthermore, treatment of the 3ASubE P-3 cells with either 12-O
      tetradecanoylphorbol 13-acetate (TPA) or 1,2-dioctanoyl-sn-glycerol (diC8), two
      different activators of protein kinase C (PKC), results in a concentration
      dependent increase in the phosphorylation of the IL-8RB. Inhibition of PKC, by
      treatment with staurosporin (50 nM for 2 h), or down-regulation of PKC, by
      prolonged treatment with TPA (400 nM for 40 h) suppresses the TPA-enhanced
      receptor phosphorylation, but has no effect on the MGSA-enhanced receptor
      phosphorylation. These data suggest that the isoforms of PKC that are sensitive
      to these manipulations may not play a role in mediating the MGSA-enhanced
      phosphorylation of the IL-8RB. TPA treatment also results in a time-dependent
      decrease in 125I-MGSA binding to the 3ASubE P-3 cells. A 30-min treatment with
      400 nM TPA results in approximately a 50% decrease in binding, whereas a 2-h
      treatment essentially eliminates specific binding of 125I-MGSA to these cells.
      The TPA-induced decrease in 125I-MGSA binding is accompanied by enhanced
      degradation of the IL-8RB, as indicated by Western blot analysis and pulse-chase
      experiments, suggesting a potential role for PKC as a negative regulator of the
      IL-8RB. MGSA treatment (50 nM for 2 h) also stimulates receptor degradation in
      the 3ASubE P-3 cells, indicating that this receptor is down-regulated in response
      to prolonged exposure to its ligand. In similar studies conducted on the
      promonocytic cell line, U937, MGSA treatment of the U937 cells resulted in
      receptor phosphorylation, whereas PKC activation failed to significantly modulate
      the phosphorylation state of the IL-8RB. Treatment of the U937 cells with MGSA,
      TPA, or diC8 resulted in a loss of receptor protein present in these cell types.
      These data imply that MGSA signaling through the IL-8RB is similar in both the
      non-hematopoietic and hematopoietic cell types, whereas activation of PKC by TPA
      or diC8 elicits different responses in these two distinct cell types.

PMID- 7737980
TI  - Molecular cloning and characterization of mouse estradiol 17 beta-dehydrogenase
      (A-specific), a member of the aldoketoreductase family.
AB  - Several mammalian livers contain monomeric 17 beta-hydroxysteroid dehydrogenase
      (17 beta-HSD) with A-stereospecificity in hydrogen transfer, which differs from
      the B-specific dimeric enzyme of human placenta in its ability to catalyze the
      oxidoreduction of xenobiotic trans-dihydrodiols of aromatic hydrocarbons and
      carbonyl compounds. Here, we report the isolation and characterization of a mouse
      cDNA clone encoding monomeric 17 beta-HSD of the liver. This clone had an entire
      coding region for a protein of 323 amino acid residues with a molecular weight of
      37,055. The deduced sequence of the protein aligned with a high degree of
      identity with rat and rabbit 20 alpha-HSDs, rat and human 3 alpha-HSD/dihydrodiol
      dehydrogenases, and bovine prostaglandin F synthase, which are members of the
      aldoketoreductase family, but was distinct from human 17 beta-HSD and carbonyl
      reductase, members of the short chain dehydrogenases. The expression of the cDNA
      in Escherichia coli resulted in synthesis of a protein that was active toward
      androgens, estrogens, and xenobiotic substrates. The recombinant and mouse liver
      17 beta-HSDs also exhibited low 20 alpha-HSD activity toward progestins, which is
      similar to bifunctional activity of human placental 17 beta-HSD. Therefore, the
      mouse enzyme was given the designation of estradiol 17 beta-dehydrogenase (A
      specific). Northern analysis of mouse tissues revealed the existence of a single
      1.7-kilobase 17 beta-HSD mRNA species in the liver, kidney, testis, and stomach.
      The liver mRNA content was considerably more abundant than those found in the
      other tissues, as 17 beta-HSD protein was mainly detected in the liver by Western
      analysis.

PMID- 7737981
TI  - Calcium stimulation of procoagulant activity in human erythrocytes. ATP
      dependence and the effects of modifiers of stimulation and recovery.
AB  - The human erythrocyte membrane is generally considered to have no procoagulant
      activity. The normal membrane is characterized as having an asymmetric
      distribution of phospholipid species such that negatively charged and
      aminophospholipids are predominantly located on the inner leaflet of the membrane
      bilayer. Elevation of cytoplasmic Ca2+ in erythrocytes produces an assortment of
      biochemical and structural responses that include diminished phospholipid
      asymmetry and an elevation in procoagulant activity. Maintenance of the normal
      asymmetric distribution of phospholipid species is believed to be largely
      mediated by a phospholipid translocase mechanism. We have utilized a recently
      developed single-step kinetic assay of procoagulant activity to investigate the
      mechanisms of Ca2+ stimulation of procoagulant activity and recovery from the
      procoagulant state upon removal of Ca2+. This study demonstrated that stimulation
      of procoagulant activity by elevated cytoplasmic Ca2+ is greatly diminished in
      ATP-depleted erythrocytes. Phospholipid translocase inhibitors failed to fully
      inhibit recovery from the procoagulant state after removal of Ca2+. The data
      indicate that recovery of endogenous lipid from a procoagulant cofiguration may
      not be entirely mediated by the phospholipid translocase. Additionally, the data
      are inconsistent with the phospholipid translocase mediating the Ca(2+)-induced
      elevation of procoagulant activity, although the involvement of other protein(s)
      is indicated.

PMID- 7737982
TI  - Transient aggregation of major histocompatibility complex class II chains during
      assembly in normal spleen cells.
AB  - Many cell surface proteins exist as complexes of multiple subunits. It is well
      established that most such complexes are assembled within the endoplasmic
      reticulum (ER). However, the mechanistic details of the assembly process are
      largely unknown. We show here that alpha and beta subunits of major
      histocompatibility complex class II antigens in spleen cells of normal mice pass
      through a transiently aggregated phase in the ER prior to assembly with the
      invariant chain (Ii). Aggregates form immediately after synthesis and disappear
      concomitantly with assembly of mature alpha beta Ii complexes. In spleen cells
      lacking Ii, aggregates fail to be efficiently dissociated over time, implicating
      subunit assembly as a requirement for disaggregation. Two ER chaperones, BiP and
      calnexin, bind to newly synthesized class II MHC chains but do not contribute
      appreciably to the large size of the aggregates. Our observations suggest that
      some subunits of multisubunit complexes pass through a transient, dynamic high
      molecular weight aggregate phase during the physiological process of assembly.
      The results further suggest a novel role for Ii in promoting stable dissociation
      of preformed aggregates containing alpha and beta subunits rather than in
      preventing their formation.

PMID- 7737983
TI  - Synthesis and metabolism of bis-diphosphoinositol tetrakisphosphate in vitro and
      in vivo.
AB  - The pathway of synthesis and metabolism of bis-diphosphoinositol
      tetrakisphosphate (PP-InsP4-PP) was elucidated by high performance liquid
      chromatography using newly available 3H- and 32P-labeled substrates. Metabolites
      were also identified by using two purified phosphatases in a structurally
      diagnostic manner: tobacco "pyrophosphatase" (Shinshi, H., Miwa, M., Kato, K.,
      Noguchi, M. Matsushima, T., and Sugimura, T. (1976) Biochemistry 15, 2185-2190)
      and rat hepatic multiple inositol polyphosphate phosphatase (MIPP; Craxton, A.,
      Ali, N., and Shears, S. B. (1995) Biochem. J. 305, 491-498). The demonstration
      that diphosphoinositol polyphosphates were hydrolyzed by MIPP provides new
      information on its substrate specificity, although MIPP did not metabolize
      significant amounts of these polyphosphates in either rat liver homogenates or
      intact AR4-2J cells. In liver homogenates, inositol hexakisphosphate (InsP6) was
      phosphorylated first to a diphosphoinositol pentakisphosphate (PP-InsP5) and then
      to PP-InsP4-PP. These kinase reactions were reversed by phosphatases,
      establishing two coupled substrate cycles. The two dephosphorylations were
      probably performed by distinct phosphatases that were distinguished by their
      separate positional specificities, and their different sensitivities to
      inhibition by F- (IC50 values of 0.03 mM and 1.4 mM against PP-InsP5 and PP-InsP4
      PP, respectively). In [3H]inositol-labeled AR4-2J cells, the steady-state levels
      of PP-[3H]InsP5 and PP-[3H]InsP4-PP were, respectively, 2-3 and 0.6% of the level
      of [3H]InsP6. The ongoing turnover of these polyphosphates was revealed by
      treatment of cells with 0.8 mM NaF for 40 min, which reduced levels of [3H]InsP6
      by 50%, increased the levels of PP-[3H]InsP5 16-fold, and increased levels of PP
      [3H]InsP4-PP 5-fold. A large increase in levels of PP-[3H]InsP5 also occurred in
      cells treated with 10 mM NaF, but then no significant change to levels of PP
      [3H]InsP4-PP were observed; there may be important differences in the control of
      the turnover of these two compounds.

PMID- 7737985
TI  - Active site residues of human brain hexokinase as studied by site-specific
      mutagenesis.
AB  - The truncated gene of hexokinase, mini-hexokinase, starting with methionine 455
      and ending at the C terminus was expressed in Escherichia coli. Mini-hexokinase
      lost its ability to ameliorate inhibition of glucose-6-P-inhibited mini
      hexokinase in the presence of phosphate (P(i)). We suggest that the P(i) site
      either resides in the N-terminal half of hexokinase I or requires the N-terminal
      portion of the enzyme. Site-directed mutagenesis was performed to obtain two
      mutants of mini-hexokinase: C606S and C628S. Both are thought to be associated
      with the active site of hexokinase I. These mutants exhibited a 3-fold increase
      in Km for glucose but no change in either the Km for ATP or the kcat. The
      circular dichroism (CD) spectra showed no differences among the wild-type or
      mutant enzymes. These results suggest that Cys606 and Cys628 are not involved in
      glucose binding directly. The putative ATP-binding site of full-length human
      brain hexokinase may involve Arg539 and Gly679, and these residues were mutated
      to Ile. For the mutant R539I, the kcat value decreased 114-fold relative to wild
      type hexokinase, whereas the Km values for ATP and glucose changed only slightly.
      No change was observed in the Ki value for 1,5-anhydroglucitol 6-phosphate. CD
      spectra showed only a slight change in secondary structure. For the mutant G679I,
      overexpressed hexokinase is insoluble. We suggest that Arg539 is important for
      catalysis because it stabilizes the transition state product ADP-hexokinase.
      Gly679 is probably important for proper folding of the protein.

PMID- 7737984
TI  - Spectroscopic evidence for reaction of prostaglandin H synthase-1 tyrosyl radical
      with arachidonic acid.
AB  - The coupling between the peroxidase and cyclooxygenase activities of
      prostaglandin H synthase (PGHS) has been proposed to be mediated by a critical
      tyrosyl radical through a branched chain mechanism (Dietz, R., Nastainczyk, W.,
      and Ruf, H. H. (1988) Eur. J. Biochem. 171, 321-328). In this study, we have
      examined the ability of PGHS isoform-1 (PGHS-1) tyrosyl radicals to react with
      arachidonate. Anaerobic addition of arachidonate following formation of the
      peroxide-induced wide doublet or wide singlet tyrosyl radical led to
      disappearance of the tyrosyl radicals and emergence of a new EPR signal, which is
      distinct from known PGHS-1 tyrosyl radicals. The new radical was clearly derived
      from arachidonate because its EPR line shape changed when 5,6,8,9,11,12,14,15
      octadeuterated arachidonate was used. Subsequent addition of oxygen to samples
      containing the fatty acyl radical resulted in regeneration of tyrosyl radical
      EPR. In contrast, the peroxide-generated tyrosyl radical in indomethacin-treated
      PGHS-1 (a narrow singlet) failed to react with arachidonate, consistent with the
      cyclooxygenase inhibition by indomethacin. These results indicate that the
      peroxide-generated wide doublet and wide singlet tyrosyl radicals serve as
      immediate oxidants of arachidonate bound at the cyclooxygenase active site to
      form a carbon-centered fatty acyl radical, which reacts with oxygen to form a
      hydroperoxide. These observations represent the first direct evidence of chemical
      coupling between the peroxidase reaction and arachidonate oxygenation in PGHS-1
      and support the proposed role for a tyrosyl radical in cyclooxygenase catalysis.

PMID- 7737986
TI  - A Ca(2+)-binding chimera of human lysozyme and bovine alpha-lactalbumin that can
      form a molten globule.
AB  - In contrast to lysozymes, which undergo two-state thermal denaturation, the
      Ca(2+)-free form of the homologous alpha-lactalbumins forms an intermediate
      "molten globule" state. To understand this difference, we have produced a chimera
      of human lysozyme and bovine alpha-lactalbumin. In the synthetic gene of the
      former the sequence coding for amino acid residues 76-102 was replaced by that
      for bovine alpha-lactalbumin 72-97, which represents the Ca(2+)-binding loop and
      the central helix C. The chimeric protein, LYLA1, expressed in Saccharomyces
      cerevisiae was homogeneous on electrophoresis and mass spectrometry. Its Ca2+
      binding constant was 2.50 (+/- 0.04) x 10(8) M-1, and its muramidase activity 10%
      of that of human lysozyme. One-dimensional NMR spectroscopy indicated the
      presence of a compact, well structured protein. From two-dimensional NMR spectra,
      main chain resonances for 118 of a total of 129 residues could be readily
      assigned. Nuclear Overhauser effect analysis and hydrogen-deuterium exchange
      measurements indicated the presence and persistence of all expected secondary
      structure elements. Thermal denaturation, measured by circular dichroism, showed
      a single transition temperature for the Ca2+ form at 90 degrees C, whereas
      unfolding of the apo form occurred at 73 degrees C in the near-UV and 81 degrees
      C in the far-UV range. These observations illustrate that by transplanting the
      central part of bovine alpha-lactalbumin, we have introduced into human lysozyme
      two important properties of alpha-lactalbumins, i.e. stabilization through Ca2+
      binding and molten globule behavior.

PMID- 7737987
TI  - Structural basis for the biological activities of bovine seminal ribonuclease.
AB  - Bovine seminal ribonuclease (BS-RNase) is a homolog of RNase A with special
      biological properties that include specific antitumor, aspermatogenic, and immuno
      suppressive activities. Unlike RNase A, BS-RNase is a dimer cross-linked by
      disulfide bonds between Cys31 of one subunit and Cys32 of the other. At
      equilibrium, this dimer is a mixture of two distinct quaternary forms, M = M and
      M x M. The conversion of M = M to M x M entails the exchange of NH2-terminal
      alpha-helices between subunits. Here, the cytotoxic activities of purified M x M
      were shown to be greater than those of purified M = M, despite extensive
      equilibration of M = M and M x M during the time course of the assays. Replacing
      Cys31 or Cys32 with a serine residue did not compromise the enzymatic activity of
      dimeric BS-RNase, but reduced both the fraction of M x M at equilibrium and the
      cytotoxicity. We conclude that the M x M form is responsible for the special
      biological properties of BS-RNase. Since cytosolic ribonuclease inhibitor binds
      tightly to monomeric but not dimeric BS-RNase and only the M x M form can remain
      dimeric in the reducing environment of the cytosol, we propose that BS-RNase has
      evolved its M x M form to retain its lethal enzymatic activity in vivo.

PMID- 7737988
TI  - Different voltage-dependent inhibition by dihydropyridines of human Ca2+ channel
      splice variants.
AB  - Voltage-dependent inhibition by 1,4-dihydropyridines is a characteristic property
      of L-type Ca2+ channels. Six out of 50 exons of the channel alpha 1C subunit gene
      are subjected to alternative splicing, thus generating channel isoform diversity.
      Using Xenopus oocytes as an expression system, we have found that transmembrane
      segment IIIS2 of human alpha 1C subunit is involved in the control of voltage
      dependence of dihydropyridine action. This segment is genetically regulated
      through alternative splicing of exons 21/22. Site-directed mutagenesis points to
      two amino acids in IIIS2, which determine the difference of the splice variants
      in their sensitivities to dihydropyridines. This finding provides new insight
      into molecular mechanisms of Ca2+ channel inhibition by this important class of
      drugs.

PMID- 7737989
TI  - X-ray absorption near edge studies of cytochrome P-450-CAM, chloroperoxidase, and
      myoglobin. Direct evidence for the electron releasing character of a cysteine
      thiolate proximal ligand.
AB  - The low spin ferric and low and high spin ferrous forms of myoglobin, bacterial
      cytochrome P-450-CAM, and chloroperoxidase have been examined by Fe-K x-ray
      absorption edge spectroscopy. The positions of the absorption edge and the shapes
      of preedge and edge regions of imidazole adducts of ferric P-450-CAM and
      chloroperoxidase are essentially the same when compared with thiolate-ligated
      ferric myoglobin. As these three protein derivatives all have six-coordinate, low
      spin, ferric hemes with axial imidazole and thiolate ligands, the superposition
      of x-ray absorption edge spectral properties demonstrates that the protein
      environment does not effect the spectra, provided one compares heme iron centers
      with identical coordination numbers, spin and oxidation states, and ligand sets.
      In contrast, a 0.96 eV difference is observed in the energy of the absorption
      edge for imidazole- and thiolate-ligated ferric myoglobin with the latter shifted
      to lower energy as observed for ferrous myoglobin states. Similarly, in the low
      spin ferric-imidazole and ferrous-CO states, the energies of the absorption edge
      for chloroperoxidase and P-450-CAM are shifted in the direction of the ferrous
      state (to lower energy) when compared with those for analogous myoglobin
      derivatives. In the deoxyferrous high spin state, comparison of the edge spectra
      of chloroperoxidase with analogous data for cytochrome P-450-CAM suggests that
      the electron density at the iron is similar for these two protein states. The
      shifts observed in the energies of the x-ray absorption edge for the thiolate
      ligated states of these proteins relative to derivatives lacking a thiolate
      ligand provide a direct measure of the electron releasing character of a thiolate
      axial ligand. These results therefore support the suggested role of the
      cysteinate proximal ligand of P-450 as a strong internal electron donor to
      promote O-O bond cleavage in the putative ferric-peroxide intermediate to
      generate the proposed ferryl-oxo "active oxygen" state of the reaction cycle.

PMID- 7737991
TI  - The translational repression mediated by the platelet-derived growth factor 2/c
      sis mRNA leader is relieved during megakaryocytic differentiation.
AB  - Expression of the platelet-derived growth factor 2/c-sis gene is highly
      restricted and controlled at multiple levels. Its structured mRNA leader, which
      is unusually long (1022 nucleotides), serves as a potent translational inhibitor.
      One of the sites of PDGF2 synthesis is megakaryocytes, implying that PDGF2
      translation efficiency is modulated during megakaryocytic differentiation. To
      study the role of the mRNA leader as a translational cis-modulator, the hybrid
      T7/vaccinia cytoplasmic expression system was used to disconnect between
      determinants controlling transcription, alternative splicing, and mRNA stability
      from those controlling translation. Chimeric transcripts in which the human
      PDGF2/c-sis mRNA leader positioned in frame upstream of a reporter gene were used
      to determine whether the mRNA leader can confer variable translational
      efficiencies during differentiation. It is demonstrated that there is a time
      window during megakaryocytic differentiation of K562 cells in which the strong
      translational inhibition by PDGF2/c-sis mRNA leader is relieved. The time course
      of the translational repression relief is similar to that of PDGF2/c-sis
      transcriptional induction during the differentiation process. A 179-nucleotides
      CG-rich fragment immediately upstream of the initiator AUG codon is necessary for
      coffering stringent modulation of the translational efficiency. In NIH3T3
      overexpressing translation initiation factor eIF4E, the inhibitory effect of the
      mRNA leader of c-sis is not relieved, suggesting that the changes in the
      translational machinery during megakaryocytic differentiation are beyond eIF4E
      activity. The possible involvement of a 5'-end-independent translational
      mechanism is discussed.

PMID- 7737990
TI  - Distinct conformational changes induced by 20-epi analogues of 1 alpha,25
      dihydroxyvitamin D3 are associated with enhanced activation of the vitamin D
      receptor.
AB  - The relative affinities of the 1 alpha,25-dihydroxyvitamin D3 (1,25-D3) analogues
      20-epi-1 alpha,25-dihydroxyvitamin D3 (IE) and 20-epi-22-oxa-24a,26a,27a-tri-homo
      1 alpha,25-dihydroxyvitamin D3 (ID) to the nuclear vitamin D receptor (VDR) are
      similar to that of 1,25-D3, but their antiproliferative action is 1000-fold
      greater. We tested whether the greater antiproliferative effect of these
      analogues is due to a differential activation of the VDR. In ROS 17/2.8 cells,
      the effective doses required to produce 50% maximal stimulation (ED50) of
      transfected reporter genes driven by either the osteocalcin or the osteopontin
      vitamin D-response elements (VDRE) were 5 x 10(-9) M, 10(-10) M, and 10(-11) M
      for 1,25-D3, ID, and IE, respectively. Similar results were obtained when
      recombinant human VDR was cotransfected into CV-1 cells with an osteocalcin VDRE
      reporter plasmid. We found that in vitro the sensitivity of 1,25-D3-induced and
      analogue-induced receptors to proteases was different. The ED50 for binding to
      VDRE, as determined by electrophoretic mobility shift assays, was significantly
      higher for 1,25-D3-induced than for analogue-induced VDR. The concentration of
      retinoid X receptor (RXR) was significantly lower in 1,25-D3-induced than
      analogue-induced VDR complexes with VDRE. We therefore conclude that IE and ID
      augment transcriptional activity of VDR more than 1,25-D3 does, by producing
      conformational changes that enhance dimerization of VDR with RXR. We suggest that
      these conformational changes are due to differences in the contact sites of the
      20-epi analogues and 1,25-D3 with the VDR.

PMID- 7737992
TI  - Botulinum neurotoxin type C cleaves a single Lys-Ala bond within the carboxyl
      terminal region of syntaxins.
AB  - Botulinum neurotoxin serotype C (BoNT/C) is a 150-kDa protein produced by
      Clostridium botulinum, which causes animal botulism. In contrast to the other
      botulinum neurotoxins that contain one atom of zinc, highly purified preparations
      of BoNT/C bind two atoms of zinc per toxin molecule. BoNT/C is a zinc
      endopeptidase that cleaves syntaxin 1A at the Lys253-Ala254 and syntaxin 1B at
      the Lys252-Ala253 peptide bonds, only when they are inserted into a lipid
      bilayer. The other Lys-Ala bond present within the carboxyl-terminal region is
      not hydrolyzed. Syntaxin isoforms 2 and 3 are also cleaved by BoNT/C, while
      syntaxin 4 is resistant. These data suggest that BoNT/C recognizes a specific
      spatial organization of syntaxin, adopted upon membrane insertion, which brings a
      selected Lys-Ala peptide bond of its carboxyl-terminal region to the active site
      of this novel metalloproteinase.

PMID- 7737993
TI  - Reversal by GroES of the GroEL preference from hydrophobic amino acids toward
      hydrophilic amino acids.
AB  - The chaperones GroEL/hsp60 are present in all prokaryotes and in mitochondria and
      chloroplasts of eukaryotic cells. They are involved in protein folding, protein
      targeting to membranes, protein renaturation, and control of protein-protein
      interactions. They interact with many polypeptides in an ATP-dependent manner and
      possess a peptide-dependent ATPase activity. GroEL/hsp60 cooperates with
      GroES/hsp10, and the productive folding of proteins by GroEL generally requires
      GroES, which appears to regulate the binding and release of substrate proteins by
      GroEL. In a recent study, we have shown that GroEL interacts preferentially with
      the side chains of hydrophobic amino acids (Ile, Phe, Val, Leu, and Trp) and more
      weakly with several polar or charged amino acids, including the strongest alpha
      helix and beta-sheet formers (Glu, Gln, His, Thr, and Tyr). In this study, we
      show that GroES reduces the specificity of GroEL for hydrophobic amino acids and
      increases its specificity for hydrophilic ones. This shift by GroES of the GroEL
      specificity from hydrophobic amino acids toward hydrophilic ones might be of
      importance for its function in protein folding.

PMID- 7737994
TI  - Physical characterization of calponin. A circular dichroism, analytical
      ultracentrifuge, and electron microscopy study.
AB  - Calponin is a thin filament-associated smooth muscle protein that has been
      suggested to play a role in the regulation of smooth muscle contraction. We have
      used circular dichroism spectroscopy, electron microscopy, and analytical
      ultracentrifugation to study the physical properties of recombinant chicken
      gizzard alpha-calponin. The alpha-helix content of alpha-calponin was estimated
      from its circular dichroism spectrum to be approximately 13%, alpha-Calponin
      melts with a single sharp transition at approximately 57 degrees C. Rotary
      shadowing electron micrographs of alpha-calponin reveal diverse shapes ranging
      from elongated rods to collapsed coils. The lengths of the rod-shaped structures
      are approximately 18 nm. Analytical ultracentrifugation studies found alpha
      calponin to be homogeneous with a monomer molecular mass of 31.4 kDa, and a s20,w
      value of 2.34 S. These data could be used to model alpha-calponin as a prolate
      ellipsoid of revolution with an axial ratio of 6.16, a length of 16.2 nm, and a
      diameter of 2.6 nm. Taken together, our results indicate that calponin is a
      flexible, elongated molecule whose contour length is sufficient to span three
      actin subunits along the long pitch helix of an F-actin filament.

PMID- 7737995
TI  - Characterization of rhodopsin mutants that bind transducin but fail to induce GTP
      nucleotide uptake. Classification of mutant pigments by fluorescence, nucleotide
      release, and flash-induced light-scattering assays.
AB  - The photoreceptor rhodopsin is a seven-transmembrane helix receptor that
      activates the G protein transducin in response to light. Several site-directed
      rhodopsin mutants have been reported to be defective in transducin activation.
      Two of these mutants bound transducin in response to light, but failed to release
      the bound transducin in the presence of GTP (Franke, R. R., Konig, B., Sakmar, T.
      P., Khorana, H. G., and Hofmann, K. P. (1990) Science 250, 123-125). The present
      study was carried out to determine the nucleotide-binding state of transducin as
      it interacts with rhodopsin mutants. Five mutant bovine opsin genes were prepared
      by site-specific mutagenesis. Three mutant genes had deletions from one
      cytoplasmic loop each: AB delta 70-71; CD delta 143-150; and EF delta 237-249.
      Two additional loop CD mutant genes were prepared: E134R/R135E had a reversal of
      a conserved charge pair, and CD r140-152 had a 13-amino acid sequence replaced by
      a sequence derived from the amino-terminal tail. Three types of assays were
      carried out: 1) a fluorescence assay of photoactivated rhodopsin (R*)-dependent
      guanosine 5'-O-(3-thiotriphosphate) uptake by transducin, 2) an assay of R*
      dependent release of labeled GDP from the alpha-subunit of transducin holoenzyme
      (Gt alpha).GDP, and 3) a light-scattering assay of R*.Gt complex formation and
      dissociation. We show that the mutant pigments, which are able to bind transducin
      in a light-dependent manner but lack the ability to activate transducin, most
      likely form R*.Gt alpha beta gamma.GDP complexes that are impaired in GDP
      release.

PMID- 7737996
TI  - Function of polypeptide chain release factor RF-3 in Escherichia coli. RF-3
      action in termination is predominantly at UGA-containing stop signals.
AB  - Two protein release factors (RFs) showing codon specificity, RF-1 (UAG, UAA) and
      RF-2 (UAA, UGA), are required for polypeptide chain termination in Escherichia
      coli. We recently reported the localization and characterization of the gene
      encoding RF-3 (prfC), a third protein component previously described as
      stimulating termination without codon specificity. RF-3 is a GTP-binding protein
      that displays much sequence similarity to elongation factor EF-G. In a
      termination assay in vitro, RF-3 lowers the Km for terminator trinucleotides and
      is thought to act in termination signal recognition. The gene prfC was identified
      by transposon insertion mutagenesis leading to enhanced nonsense suppression of
      UGA. We report here that (i) RF-3 inactivation significantly enhances the
      suppression of termination in vivo only at UGA-dependent stop signals; (ii) the
      codon-dependent contribution to the stimulation of fMet release in vitro by RF-3
      is significantly greater with UGA termination triplet than UAG termination
      triplet; (iii) RF-3 increases dramatically the affinity of RF-2 to the UGA
      termination complex in vitro but not that of RF-1 to the UAG termination complex;
      (iv) RF-3 inactivation leads to a positive feedback on the autoregulation of RF-2
      synthesis in vivo, dependent on the competition between frameshifting and
      termination. These findings are discussed in terms of the mechanism of
      involvement of RF-3 in translation termination.

PMID- 7737997
TI  - Ligand modulates the interaction of thyroid hormone receptor beta with the basal
      transcription machinery.
AB  - We investigated the molecular mechanisms underlying the transcriptional silencing
      and the hormone-induced activation of target genes by thyroid hormone receptor
      beta (TR-beta). We developed a cell-free transcription system containing HeLa
      cell nuclear extracts in which unliganded human TR-beta represses basal
      transcription from a promoter bearing thyroid hormone response elements. Binding
      of hormonal ligand to the receptor reverse this transcriptional silencing.
      Specific binding of TR-beta to the thyroid hormone response element at the target
      promoter is crucial for silencing. Studies employing TR-beta mutants indicate
      that the silencing activity is located within the C-terminal rather than the N
      terminal domain of the receptor. Our studies reveal further that unliganded TR
      beta inhibits the assembly of a functional transcription preinitiation complex
      (PIC) at the target promoter. We postulate that interaction with TR-beta impairs
      the function(s) of one or more assembling transcriptional complexes during the
      multistep assembly of a PIC. Consistent with this hypothesis, we observe that, in
      the absence of thyroid hormone, TR-beta or a heterodimer of TR-beta and retinoid
      X-receptor undergoes direct protein-protein interactions with the transcription
      factor IIB-TATA binding protein complex, an early intermediate during PIC
      assembly. Binding of hormone to TR-beta dramatically reduces the interaction
      between the receptor and the transcription factor IIB-TATA binding protein
      complex. We propose that the role of ligand is to facilitate the assembly of
      functional PICs at the target promoter by reducing nonproductive interactions
      between TR-beta and the initiation factors.

PMID- 7737998
TI  - Thermophilic bacilli have split cytochrome b genes for cytochrome b6 and subunit
      IV. First cloning of cytochrome b from a gram-positive bacterium (Bacillus
      stearothermophilus).
AB  - The genes of Bacillus stearothermophilus K1041 encoding cytochrome b(6) (Bacillus
      cytochrome b is referred to as cytochrome b(6) for its resemblance to plastid b6)
      and subunit IV of the quinol:cytochrome c oxidoreductase (bc1 complex) were
      cloned and sequenced. For preparation of the probe for cloning, polymerase chain
      reaction was carried out using oligonucleotide mixtures targeting for N-terminal
      regions of cytochrome bc and subunit IV of the thermophilic Bacillus PS3. The
      deduced amino acid sequences contained 224 residues of 25,425 daltons for
      cytochrome b(6) and 173 residues of 19,371 daltons for subunit IV, and both open
      reading frames were separated by 67 base pairs. Cytochrome b and subunit IV
      contained 4 and 3 hydrophobic transmembrane segments, respectively, indicating
      that the fourth segment of subunit IV (eighth segment of cytochrome b) is
      lacking. Four histidine residues supposed to ligand two protohemes were
      conserved, but the two His in the fourth segment were separated by 14 amino acid
      residues like cytochrome b6, not like mitochondrial cytochrome b. The residues
      that might have conferred the two quinol-binding sites were mostly conserved, but
      especially the third His residue in the fourth segment of mitochondrial
      cytochrome b was replaced by Arg in Bacillus cytochrome b6 as in cytochrome b6.
      These characteristics and quantitative comparison of the protein sequences
      indicate that this Bacillus sequence is unique and meanwhile rather close to the
      cyanobacteria-plastids type than the purple bacteria-mitochondria type.

PMID- 7737999
TI  - Processing of transforming growth factor beta 1 precursor by human furin
      convertase.
AB  - Proteolytic processing of the transforming growth factor beta precursor (pro-TGF
      beta) is an essential step in the formation of the biologically active TGF beta
      homodimeric protein (TGF beta). The 361-amino-acid precursor pro-TGF beta 1 has
      within its primary structure the R-H-R-R processing signal found in many
      constitutively secreted precursor proteins and potentially recognized by members
      of the mammalian convertase family of endoproteases. To determine whether
      cleavage of pro-TGF beta 1 can be achieved by the furin convertase in vitro,
      purified precursor was incubated in the presence of a truncated/secreted form of
      the enzyme. Immunoblots showed that the 55-kDa pro-TGF beta 1 was converted into
      the 44 and 12.5 kDa bands corresponding to the pro-region and the mature monomer,
      respectively. Treatment of pro-TGF beta 1 with furin resulted in a 5-fold
      increase in the production of biologically active TGF beta 1. Furthermore, when
      expressed in the furin-deficient LoVo cells, no processing of pro-TGF beta 1 was
      observed. In contrast, efficient processing was observed when pro-TGF beta was
      coexpressed with the furin convertase. Collectively, these results provide
      evidence that in our experimental systems the TGF beta 1 precursor is efficiently
      and correctly processed by human furin thus permitting release of the
      biologically active peptide.

PMID- 7738000
TI  - Protein-tyrosine phosphatase inhibitors block tumor necrosis factor-dependent
      activation of the nuclear transcription factor NF-kappa B.
AB  - Most of the inflammatory and proviral effects of tumor necrosis factor (TNF) are
      mediated through the activation of the nuclear transcription factor NF-kappa B.
      How TNF activates NF-kappa B, however, is not well understood. We examined the
      role of protein phosphatases in the TNF-dependent activation of NF-kappa B.
      Treatment of human myeloid ML-1a cells with TNF rapidly activated (within 30 min)
      NF-kappa B; this effect was abolished by treating cells with inhibitors of
      protein-tyrosine phosphatase (PTPase), including phenylarsine oxide (PAO),
      pervanadate, and diamide. The inhibition was dependent on the dose and occurred
      whether added before or at the same time as TNF. PAO also inhibited the
      activation even when added 15 min after the TNF treatment of cells. In contrast
      to inhibitors of PTPase, okadaic acid and calyculin A, which block serine
      threonine phosphatase, had no effect. The effect of PTPase inhibitors was not due
      to the modulation of TNF receptors. Since both dithiothreitol and
      dimercaptopropanol reversed the inhibitory effect of PAO, critical sulfhydryl
      groups in the PTPase must be involved in NF-kappa B activation by TNF. PTPase
      inhibitors also blocked NF-kappa B activation induced by phorbol ester, ceramide,
      and interleukin-1 but not that activated by okadaic acid. The degradation of I
      kappa B protein, a critical step in NF-kappa B activation, was also abolished by
      the PTPase inhibitors as revealed by immunoblotting. Thus, overall, we
      demonstrate that PTPase is involved either directly or indirectly in the pathway
      leading to the activation of NF-kappa B.

PMID- 7738001
TI  - Characterization of mutants affecting the KRK sequence in the carboxyl-terminal
      domain of lac repressor.
AB  - The lac repressor carboxyl-terminal region is required for tetramer assembly and
      protein stability. To further investigate this region, especially the unusual
      sequence KRK, four deletion mutants eliminating the carboxyl-terminal 34, 35, 36,
      and 39 amino acids and five substitution mutants at the position of Arg-326,
      R326K, R326A, R326E, R326L, and R326W, were constructed using site-specific
      mutagenesis. The -34-amino-acid (aa) mutant, missing the most carboxyl-proximal
      lysine from the KRK sequence, exhibited lower affinity for both operator and
      inducer and lower protein stability than dimeric proteins studied previously. The
      -35-aa mutant with RK missing, as well as -36 aa and -39 aa, for which the entire
      KRK sequence was deleted, yielded inactive polypeptides that could be detected
      only by monoclonal antibody for lac repressor. In the Arg-326 mutant proteins,
      operator binding affinity was decreased by approximately 6-fold, the shift in
      inducer binding at elevated pH was diminished, and protein stability was
      decreased. Dramatic decreases in protein expression and stability occurred with
      substitution at position 326 by glutamate, leucine, or tryptophan. These results
      suggest that Arg-326 plays an important role in the formation of the proper
      tertiary structure necessary for inducer and operator affinity and for protein
      stability.

PMID- 7738002
TI  - The importance of the N-terminal segment for DnaJ-mediated folding of rhodanese
      while bound to ribosomes as peptidyl-tRNA.
AB  - Two lines of evidence indicate the importance of the N-terminal portion of
      rhodanese for correct folding of the nascent ribosome-bound polypeptide. A mutant
      gene lacking the codons for amino acids 1-23 of the wild-type protein is
      expressed very efficiently by coupled transcription/translation on Escherichia
      coli ribosomes; however, the mutant protein that is released from the ribosomes
      is enzymatically inactive. The mutant protein does not undergo the reaction that
      is promoted by the bacterial chaperone, DnaJ, which appears to be essential for
      folding of ribosome-bound rhodanese into the native conformation. The effect of
      DnaJ is monitored by fluorescence from coumarin cotranslationally incorporated at
      the N terminus of nascent rhodanese. Secondly, a synthetic peptide corresponding
      to the N-terminal 17 amino acids of the wild-type protein interferes with the
      synthesis of wild-type rhodanese but has much less effect on the synthesis of the
      N-terminal deletion mutant. The N-terminal peptide inhibits the effect of DnaJ on
      the nascent wild-type rhodanese and blocks the chaperone-mediated release and
      activation of ribosome-bound full-length rhodanese polypeptides that accumulate
      during in vitro synthesis. The results lead to the hypothesis that the N-terminal
      segment of rhodanese is required for its chaperone-dependent folding on the
      ribosome.

PMID- 7738003
TI  - The RCC1 protein interacts with Ran, RanBP1, hsc70, and a 340-kDa protein in
      Xenopus extracts.
AB  - RCC1 is an abundant, highly conserved, chromatin-associated protein whose
      function is necessary for the preservation of a properly ordered cell cycle. RCC1
      is also necessary for numerous nuclear processes, including nuclear transport and
      RNA metabolism; and it functions enzymatically as a guanine nucleotide exchange
      factor for a small, ras-related GTPase called Ran. Studies in several organisms
      suggest that RCC1 may be part of a large complex containing multiple proteins.
      There is also evidence that RCC1 associates with chromatin through other proteins
      and that the binding of the complex to chromatin varies within the cell cycle. In
      order to characterize this putative complex, we have identified a number of other
      proteins as candidate components of the complex by their association with a GST
      RCC1 fusion protein. Three of these proteins have previously been identified
      (Ran, RanBP1, and hsc70). The fourth protein is novel and has a molecular mass of
      340 kDa. In this report, we discuss a preliminary characterization of the
      interactions between these proteins.

PMID- 7738004
TI  - Heterotypic Fc gamma R clusters evoke a synergistic Ca2+ response in human
      neutrophils.
AB  - Both Fc gamma receptors on human neutrophils (Fc gamma RIIa and Fc gamma RIIIb)
      are capable of initiating signal transduction after multivalent cross-linking.
      However, immune complexes most likely activate neutrophils by a combined
      homotypic and heterotypic cross-linking of Fc gamma Rs. We have investigated the
      effect of homotypic and heterotypic Fc gamma R cluster formation on changes in
      the intracellular free Ca2+ concentration. Combined heterotypic and homotypic
      cluster formation resulted in a Ca2+ response that was strongly enhanced as
      compared to the sum of both individual Fc gamma R responses. This synergistic
      response was caused by the formation of heterotypic clusters of Fc gamma Rs and
      not by the simultaneous formation of homotypic clusters. This conclusion was
      supported by experiments with a bispecific antibody binding to both Fc gamma RIIa
      and Fc gamma RIIIb. The heterotypic Fc gamma R cross-linking results in efficient
      activation of Ca2+ influx, probably caused by a more pronounced depletion of
      intracellular Ca2+ stores. Stimulation with immune complexes also induced Ca2+
      influx in normal neutrophils, but not in Fc gamma RIIIb-deficient neutrophils.
      The synergism between both Fc gamma Rs was also apparent in other responses of
      neutrophils, such as the activation of the respiratory burst. This study shows
      that the two different Fc gamma Rs on neutrophils complement each other in
      mediating an important cellular response.

PMID- 7738005
TI  - Cloning of a differentially expressed I kappa B-related protein.
AB  - We have cloned a cDNA corresponding to a novel gene from a human epithelial cell
      line by subtractive hybridization and polymerase chain reaction techniques. This
      gene is expressed at the message level and at the protein level in a lung
      alveolar type II-like epithelial cell line but not in lung fibroblasts. In adult
      human tissues, the mRNA for this gene was detected only in the heart and the
      skeletal muscle, but not in the brain, placenta, whole lung, liver, or kidney. We
      have named this gene I kappa BR (for I kappa B-related) since its 52-kDa protein
      product has significant homology to the I kappa B family of proteins which
      function as inhibitory cytoplasmic retention proteins for the vertebrate rel/NF
      kappa B transcription factors. Although the important role of NF-kappa B in gene
      activation in cells of the immune system is now well established, a similar role
      in other cell types or in vertebrate development is less clear. The deduced amino
      acid sequence of I kappa BR has the most significant homology to the Drosophila
      protein Cactus which inhibits the function of the NF-kappa B-like protein Dorsal.
      In electrophoretic mobility shift experiments, I kappa BR inhibited the ability
      of the p50:p65 NF-kappa B heterodimer to bind DNA. The DNA binding ability of the
      p50 homodimer but not the p65 homodimer was drastically inhibited by I kappa BR.
      In transfection experiments, overexpression of I kappa BR significantly inhibited
      NF-kappa B-dependent transcription from the Ig kappa enhancer. This new member of
      the I kappa B family of proteins, I kappa BR, may play an important role in
      regulation of NF-kappa B function in epithelial cells.

PMID- 7738006
TI  - Binding of low affinity N-formyl peptide receptors to G protein. Characterization
      of a novel inactive receptor intermediate.
AB  - G protein-coupled seven-transmembrane-containing receptors, such as the N-formyl
      peptide receptor (FPR) of neutrophils, likely undergo a conformational change
      upon binding of ligand, which enables the receptor to transmit a signal to G
      proteins. We have examined the functional significance of numerous conserved
      charged amino acid residues proposed to be located within or near the
      transmembrane domains. Whereas the wild type FPR exhibits a Kd for an agonist of
      1-3 nM, which is reduced to approximately 40 nM in the presence of guanosine 5'-3
      O-(thio)triphosphate (GTP gamma S), substitution of either Asp71 or Arg123
      resulted in mutant receptors that bound ligand with only low affinity (Kd = 30-50
      nM) independent of GTP gamma S. In contrast, substitution of Arg163, predicted to
      be located at a similar depth within the membrane as Asp71, had no effect on
      ligand binding. Replacement of residues Arg309-Glu310-Arg311 resulted in an FPR
      with intermediate ligand binding characteristics. Functional analysis of the
      mutant receptors revealed that substitution of either Asp71 or Arg123 resulted in
      a mutant receptor that was unable to mediate calcium mobilization, whereas
      replacement of residues Arg309-Glu310-Arg311 yielded a receptor with an EC50 of
      50 nM, compared with 0.5 nM for the wild type FPR. In order to determine the
      point of the defect in signal transduction, we performed reconstitution of the
      solubilized receptors with purified G proteins. The wild type FPR displayed a Kd
      for G protein of approximately 0.6 microM compared with the Arg309/Glu310/Arg311
      mutant with a Kd of approximately 30 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738007
TI  - Spinach chloroplast cpn21 co-chaperonin possesses two functional domains fused
      together in a toroidal structure and exhibits nucleotide-dependent binding to
      plastid chaperonin 60.
AB  - Chloroplasts contain a 21-kDa co-chaperonin polypeptide (cpn21) formed by two
      GroES-like domains fused together in tandem. Expression of a double-domain
      spinach cpn21 in Escherichia coli groES mutant strains supports growth of
      bacteriophages lambda and T5, and will also suppress a temperature-sensitive
      growth phenotype of a groES619 strain. Each domain of cpn21 expressed separately
      can function independently to support bacteriophage lambda growth, and the N
      terminal domain will additionally suppress the temperature-sensitive growth
      phenotype. These results indicate that chloroplast cpn21 has two functional
      domains, either of which can interact with GroEL in vivo to facilitate
      bacteriophage morphogenesis. Purified spinach cpn21 has a ring-like toroidal
      structure and forms a stable complex with E. coli GroEL in the presence of ADP
      and is functionally interchangeable with bacterial GroES in the chaperonin
      facilitated refolding of denatured ribulose-1,5-bisphosphate carboxylase. Cpn21
      also inhibits the ATPase activity of GroEL. Cpn21 binds with similar efficiency
      to both the alpha and beta subunits of spinach cpn60 in the presence of adenine
      nucleotides, with ATP being more effective than ADP. The tandemly fused domains
      of cpn21 evolved early and are present in a wide range of photosynthetic
      eukaryotes examined, indicating a high degree of conservation of this structure
      in chloroplasts.

PMID- 7738008
TI  - Developmental stage-specific regulation of Xenopus tRNA genes by an upstream
      promoter element.
AB  - Typically the internal promoter elements of tRNA genes are necessary and
      sufficient to support transcription. Here a sequence element preceding a Xenopus
      tRNA gene is shown to be required for transcription in late stage, but not early
      stage oocyte extracts. The constitutive tyrD gene is expressed in both early and
      late oocyte extracts, whereas the early oocyte-specific tyrCooc gene is only
      expressed in early extracts. An upstream promoter element (URR), between
      positions -42 and -14 of the tyrD gene, mediates this differential expression.
      The URR is required for tyrD transcription in late oocyte extracts. Placing the
      URR upstream of the tyrCooc gene allows this gene to be transcribed in late
      extracts. The URR is irrelevant to transcription in early extracts; transcription
      of tyrD or tyrCooc requires only the internal promoter sequences. This indicates
      the polymerase III transcriptional machinery changes during oogenesis, resulting
      in a stringent upstream sequence requirement. Mutations within the URR are shown
      to alter the preferred site of initiation by RNA polymerase III. Shifting the
      position of the URR upstream by one-half helical turn also repositioned the site
      of initiation, suggesting the URR directs the placement of the initiation factor
      complex or polymerase itself.

PMID- 7738009
TI  - Recognition of the structure around the site of cleavage by the carboxyl-terminal
      processing protease for D1 precursor protein of the photosystem II reaction
      center.
AB  - In order to analyze the structural requirement(s) for proteolytic cleavage,
      synthetic oligopeptides corresponding to the carboxyl-terminal (COOH-terminal)
      sequence of the precursor to the D1 protein (pD1) of the photosystem II reaction
      center, with or without substituted side chain(s) around the cleavage site, were
      subjected to enzymatic analysis with partially purified processing protease from
      spinach. The efficiency of action as a competitive inhibitor of the enzymatic
      cleavage of the COOH-terminal extension, as well as the capacity to serve as a
      substrate, was used as an indication of effective binding to the protease.
      Neither a COOH-terminal fragment consisting of the 9 amino acids that are cleaved
      from pD1 by the protease nor a COOH-terminal fragment of the mature protein
      consisting of 15 amino acids inhibited the enzymatic processing of pD1. By
      contrast, a COOH-terminal fragment of pD1 consisting of 24 amino acids, which
      included the sequences of both the COOH-terminal extension and the COOH-terminal
      15 amino acids of the mature protein, was effective both as a competitive
      inhibitor and as a substrate. This result suggests that the structure formed by
      linkage between these two parts of the protein moiety is important in the
      substrate-enzyme interaction. Among substitutions around the cleavage site, the
      replacement of Leu-343 by Ala (L343A) specifically destroyed the ability of the
      oligopeptide to serve as either a substrate or an inhibitor, suggesting that the
      presence of the hydrophobic Leu residue is crucial for the formation of the
      recognition site. A series of six substitutions at Ala-345 had marked effects on
      the value of Vmax, without affecting the binding affinity, as represented by Km;
      the order of substitutions at residue 345 in terms of their effects on Vmax was
      Ala,Ser,Phe,Cys > Gly > Val >> Pro. With a Pro residue at position 345, the
      oligopeptide was practically inactive as a substrate.

PMID- 7738010
TI  - A 68-kDa kinase and NADPH oxidase component p67phox are targets for Cdc42Hs and
      Rac1 in neutrophils.
AB  - Cdc42Hs and Rac1 are members of the Ras superfamily of small molecular weight
      (p21) GTP binding proteins. Cdc42Hs induces filopodia formation in Swiss 3T3
      fibroblasts while Rac1 induces membrane ruffling. Rac1 also activates superoxide
      production by the components (cytochrome b, p40phox, p67phox, and p47phox) of the
      neutrophil oxidase. To isolate target proteins involved in these signaling
      pathways, we have probed proteins from neutrophil cytosol immobilized on
      nitrocellulose with Cdc42Hs labeled with [gamma-32P]GTP. Cdc42Hs probe detected
      binding protein(s) of 66-68 kDa in neutrophil cytosol. Rac1 probe also detected
      the 66-68-kDa proteins, suggesting the possibility that p67phox may be a binding
      protein for both of these p21 proteins. Indeed, Cdc42Hs and Rac1 were found to
      bind specifically to purified recombinant p67phox but not the other oxidase
      components. A 68-kDa Cdc42Hs binding protein was purified from neutrophil cytosol
      and found to be related to the recently described p65pak kinase from brain. These
      results suggest that the p68 kinase and p67phox are targets for Cdc42Hs and Rac1
      in neutrophils.

PMID- 7738012
TI  - Mouse interleukin-2 receptor alpha gene expression. Delimitation of cis-acting
      regulatory elements in transgenic mice and by mapping of DNase-I hypersensitive
      sites.
AB  - The alpha chain of the interleukin-2 receptor (IL-2R alpha) is a key regulator of
      lymphocyte proliferation. To analyze the mechanisms controlling its expression in
      normal cells, we used the 5'-flanking region (base pairs -2539/+93) of the mouse
      gene to drive chloramphenicol acetyltransferase expression in four transgenic
      mouse lines. Constitutive transgene activity was restricted to lymphoid organs.
      In mature T lymphocytes, transgene and endogenous IL-2R alpha gene expression was
      stimulated by concanavalin A and up-regulated by IL-2 with very similar kinetics.
      In thymic T cell precursors, IL-1 and IL-2 cooperatively induced transgene and IL
      2R alpha gene expression. These results show that regulation of the endogenous IL
      2R alpha gene occurs mainly at the transcriptional level. They demonstrate that
      cis-acting elements in the 5'-flanking region present in the transgene confer
      correct tissue specificity and inducible expression in mature T cells and their
      precursors in response to antigen, IL-1, and IL-2. In a complementary approach,
      we screened the 5' end of the endogenous IL-2R alpha gene for DNase-I
      hypersensitive sites. We found three lymphocyte specific DNase-I hypersensitive
      sites. Two, at -0.05 and -5.3 kilobase pairs, are present in resting T cells. A
      third site appears at -1.35 kilobase pairs in activated T cells. It co-localizes
      with IL-2-responsive elements identified by transient transfection experiments.

PMID- 7738011
TI  - Regulation of the uncoupling protein gene (Ucp) by beta 1, beta 2, and beta 3
      adrenergic receptor subtypes in immortalized brown adipose cell lines.
AB  - Immortalized brown adipocyte cell lines derived from a mouse hibernoma express
      all three beta-adrenergic receptor subtypes, including beta 3-adrenergic receptor
      (AR). In response to norepinephrine, cAMP production by plasma membranes from
      four clonal cell lines was stimulated to levels comparable with brown adipocytes
      isolated from interscapular brown adipose tissue (72.8-89.6 versus 97.8 pmol
      cAMP/min/mg of protein, respectively). All cell lines responded to the highly
      selective beta 3-adrenergic receptor agonist CL316,243 by stimulating adenylyl
      cyclase activity (3-10-fold over basal). beta 1-, beta 2-, and beta 3-adrenergic
      receptor mRNA was detected by Northern blotting and/or reverse transcriptase
      polymerase chain reaction. Competition binding assays with the antagonists
      CGP20712A and 125I-cyanopindolol showed the proportions of beta 1AR and beta 2AR
      in immortalized cells to be similar to brown adipocytes from tissue (cells: 35%
      beta 1AR, 65% beta 2AR; brown adipocytes from tissue: beta 1AR 41%, 59% beta
      2AR). Expression of brown fat-specific mitochondrial uncoupling protein (Ucp) was
      stimulated by beta-adrenergic agonists in two of the four cell lines. The ability
      of individual beta AR subtypes to regulate Ucp expression was examined with
      combinations of selective beta-adrenergic agonists and antagonists. Expression of
      Ucp could be induced by any of the beta-adrenergic receptor subtypes. However,
      the greatest response was obtained by stimulating all three beta-adrenergic
      receptor subtypes simultaneously (100 microM isoproterenol). Incubation of
      membranes from cultured cells or brown adipocytes from tissue with CL316,243 at
      an optimal concentration (5 microM) did not prevent norepinephrine from further
      stimulating adenylyl cyclase activity, suggesting that the combined activation of
      beta 1AR/beta 2AR, plus beta 3AR, together produced an additive cAMP response.
      Multiple forms of adenylyl cyclase were identified in brown and white adipocyte
      cell lines and tissues. Northern blot analysis detected adenylyl cyclase types 5,
      6, and 10. Screening of reverse transcriptase-PCR products by DNA sequencing
      confirmed the identities of these forms and lower levels of additional isoforms,
      raising the possibility that beta-adrenergic receptor subtypes in adipocytes
      couple to distinct adenylyl cyclases. Because these cell lines display functional
      and phenotypic similarities to interscapular brown adipocytes, they will be a
      useful model to study the regulation of beta-adrenergic receptor expression and
      function, and the control of Ucp expression and activity.

PMID- 7738013
TI  - Mouse interleukin-2 receptor alpha gene expression. Interleukin-1 and interleukin
      2 control transcription via distinct cis-acting elements.
AB  - We have shown that interleukin-1 (IL-1) and IL-2 control IL-2 receptor alpha (IL
      2R alpha) gene transcription in CD4-CD8- murine T lymphocyte precursors. Here we
      map the cis-acting elements that mediate interleukin responsiveness of the mouse
      IL-2R alpha gene using a thymic lymphoma-derived hybridoma (PC60). The
      transcriptional response of the IL-2R alpha gene to stimulation by IL-1 + IL-2 is
      biphasic. IL-1 induces a rapid, protein synthesis-independent appearance of IL-2R
      alpha mRNA that is blocked by inhibitors of NF-kappa B activation. It also primes
      cells to become IL-2 responsive and thereby prepares the second phase, in which
      IL-2 induces a 100-fold further increase in IL-2R alpha transcripts. Transient
      transfection experiments show that several elements in the promoter-proximal
      region of the IL-2R alpha gene contribute to IL-1 responsiveness, most
      importantly an NF-kappa B site conserved in the human and mouse gene. IL-2
      responsiveness, on the other hand, depends on a 78-nucleotide segment 1.3
      kilobases upstream of the major transcription start site. This segment functions
      as an IL-2-inducible enhancer and lies within a region that becomes DNase I
      hypersensitive in normal T cells in which IL-2R alpha expression has been
      induced. IL-2 responsiveness requires three distinct elements within the
      enhancer. Two of these are potential binding sites for STAT proteins.

PMID- 7738014
TI  - Repression of the c-Jun trans-activation function by the adenovirus type 12 E1A
      52R protein correlates with the inhibition of phosphorylation of the c-Jun
      activation domain.
AB  - The early region 1A 52R polypeptide, a protein expressed exclusively by the in
      vivo oncogenic adenovirus subtype 12, represses the trans-activating function of
      the cellular transcription factor complex AP-1 consisting of c-Jun-c-Jun
      homodimers. In this report we demonstrate that the repression in vivo correlates
      with a direct physical interaction of the adenovirus protein with c-Jun in vitro.
      Interestingly, the 52R protein binds to the bZIP domain of c-Jun essential for
      dimerization and DNA binding but not to the c-Jun activation domain. This
      interaction does not prevent the promoter binding of c-Jun/AP-1. Moreover, the
      physical association between c-Jun and the TATA box-binding protein TBP is not
      disturbed by the 52R polypeptide. In fact, we show evidence that down-regulation
      of c-Jun activity by the adenoviral protein is due to the inhibition of
      phosphorylation of the c-Jun trans-activation domain. In vivo phosphorylation of
      the c-Jun activation domain is necessary for the interaction of c-Jun with
      specific cofactors such as CBP and therefore a prerequisite for the activation of
      target genes. Due to these results we propose a model in which the 52R protein
      represses the trans-activating function of c-Jun by preventing its
      phosphorylation through a specific kinase necessary for the activation of the
      cellular transcription factor.

PMID- 7738016
TI  - The proximal promoter of the mouse loricrin gene contains a functional AP-1
      element and directs keratinocyte-specific but not differentiation-specific
      expression.
AB  - Loricrin gene expression is limited to terminally differentiating keratinocytes
      of stratified squamous epithelia. To define the regulatory elements that mediate
      the expression of the loricrin gene, we replaced the loricrin coding sequences
      from a 6.5-kilobase genomic fragment with the chloramphenicol acetyltransferase
      gene and transfected this construct into cultured mouse keratinocytes. High
      expression levels were observed in both undifferentiated as well as
      differentiating cells. Transgenic mice bearing a similar construct, but with beta
      galactosidase as the reporter gene, corroborated these in vitro findings and
      showed tissue- and cell type-specific, but not differentiation-specific
      expression. Deletion analysis of the promoter region determined that sequences up
      to -60 base pairs from the start of transcription could be removed without
      significant loss of promoter activity. Within these proximal 60 base pairs is an
      evolutionarily conserved AP-1 element that is recognized by both purified c-Jun
      and AP-1 factors from keratinocytes in vitro. Mutation of this AP-1 site
      abolished the activity of the loricrin promoter. These studies show that elements
      directing expression of the loricrin gene to the stratified squamous epithelia
      are contained within a 6.5-kilobase genomic fragment, and those elements required
      to restrict expression to differentiated keratinocytes lie outside this region.

PMID- 7738015
TI  - Cloning and expression of a murine fascin homolog from mouse brain.
AB  - The fascins are a widely distributed family of proteins that organize filamentous
      actin into bundles. We have cloned, sequenced, and expressed the murine homolog.
      Fascin is most abundant in brain and is found in other tissues including uterus
      and spleen. The deduced open reading frame encodes a protein of 493 amino acids
      with a molecular mass of 54,412 Da. Previous solubility problems with bacterially
      expressed fascins were overcome by producing the mouse protein as a fusion with
      Escherichia coli thioredoxin. A method for cleaving the fusion protein and for
      purifying active recombinant fascin is described. The N-terminal sequence and
      molecular mass estimated on SDS gels indicate that recombinant fascin is full
      length. Two-dimensional gel electrophoresis suggests that recombinant fascin is
      post-translationally modified in a manner similar to that observed in mouse
      brain. Recombinant fascin and the fusion protein are recognized by monoclonal
      anti-fascin antibodies and will bundle rabbit skeletal muscle F-actin in vitro at
      a stoichiometry of 4.1:1 actin to fascin. Electron cryomicroscopy images show
      that the reconstituted bundles are highly ordered. However, their fine structure
      differs from that of echinoid fascin-actin bundles. This structural difference
      can be attributed to fascin.

PMID- 7738017
TI  - Protein phosphatases 1 and 2A regulate the transcriptional and DNA binding
      activities of retinoic acid receptors.
AB  - To determine which factors may regulate the DNA binding and transcriptional
      properties of retinoic acid receptors (RARs and RXRs), we investigated the
      sensitivity of reporter genes bearing various retinoic acid response elements
      (RAREs) to protein phosphatases (PPases) inhibition. PPases inhibition by okadaic
      acid led to an increase of the reporter genes activity in a RARE-dependent and
      ligand-independent manner and was dependent on the type of response element used.
      Overexpression of protein phosphatases 2A and 1 (PP2A and PP1) decreased the
      inducibility of the reporter genes tested. Nuclear extracts from okadaic acid
      treated COS cells displayed an 2-5-fold increased level of receptor binding to
      RAREs in vitro, suggesting that PPases inhibition increased the DNA binding
      activity of retinoid receptors. Treatment of receptors extracted from COS cells
      by alkaline phosphatase and partially purified PP1 and PP2A decreased their DNA
      binding activity, but heterodimers bound to DNA were not sensitive to phosphatase
      treatment. Reconstitution experiments showed that phosphorylation of both
      receptors increased the DNA binding activity of RXR/RAR heterodimers. Taken
      together, these data show that the modulation of the phosphorylation state of
      RARs and RXRs represents an other level of regulation of the retinoid signaling
      pathway.

PMID- 7738018
TI  - Furin-induced cleavage and activation of Shiga toxin.
AB  - Shiga toxin has a single A subunit non-covalently associated with a pentamer of B
      subunits. The toxin has a trypsin-sensitive region near the COOH-terminal end of
      the A-chain, and upon cleavage, two disulfide bonded fragments, A1 and A2, are
      generated. These fragments are also formed upon incubation with cells. The
      disulfide loop contains the sequence (Arg-X-X-Arg), which is a consensus motif
      for cleavage by the membrane-anchored protease furin. We found that a soluble
      form of furin cleaves intact A-chain producing A1 and A2 fragments, and furin
      also seems to be responsible for rapid cellular cleavage of Shiga toxin. LoVo
      cells, which normally do not produce functional furin, cleave intact A-chain very
      efficiently when transfected with furin (LoVo/fur), whereas a control cell
      (LoVo/neo) cleaves the toxin very slowly. To investigate the role of this
      cleavage for intoxication of cells, we studied the ability of unnicked and furin
      nicked toxin to inhibit protein synthesis in LoVo/fur and LoVo/neo cells.
      LoVo/fur cells were intoxicated equally well with unnicked and nicked toxin,
      whereas in LoVo/neo cells nicked toxin was about 20 times more active than
      unnicked toxin. The results suggest that cleavage of Shiga toxin is important for
      intoxication of cells, and they indicate that furin can cleave and thereby
      activate Shiga toxin in cells.

PMID- 7738019
TI  - Interaction of the von Willebrand factor (vWF) with collagen. Localization of the
      primary collagen-binding site by analysis of recombinant vWF a domain
      polypeptides.
AB  - The von Willebrand factor (vWF) mediates platelet adhesion to the vascular
      subendothelium by binding to collagen, other matrix constituents, and the
      platelet receptor glycoproteins Ib/IX and IIb/IIIa. Although substantial progress
      has been made in defining vWF structure-function relationships, there are
      conflicting data regarding the location of its collagen-binding site(s). Possible
      collagen-binding sites have been localized in the A1 and A3 domains of vWF. To
      study the proposed binding sites, we have expressed cDNA sequences encoding the
      A1 and A3 domains of vWF in Escherichia coli and purified the resulting proteins
      from bacterial inclusion bodies. In addition, a chimeric molecule containing
      residues 465-598 of the vWF A1 domain polypeptide (vWF-A1) fused in frame to
      residues 1018-1114 of the vWF A3 domain polypeptide (vWF-A3) was also expressed.
      Each of the three recombinant proteins purified as a monomer and contained a
      single disulfide bond. As previously reported (Cruz, M. A., Handin, R. I., and
      Wise, R. J. (1993) J. Biol. Chem. 268, 21238-21245), recombinant vWF-A1 inhibited
      ristocetin-induced platelet agglutination, but did not compete with vWF multimers
      for collagen binding. In contrast, vWF-A3 inhibited the binding of multimeric vWF
      to immobilized collagen, but did not inhibit ristocetin-induced platelet
      agglutination. Metabolically labeled vWF-A3 bound to immobilized collagen in a
      saturable and reversible manner with a Kd of 1.8 x 10(-6) M. The vWF-A1/A3
      chimera was bifunctional. It inhibited vWF binding to platelet glycoprotein Ib/IX
      with an IC50 of 0.6 x 10(-6) M and inhibited vWF binding to collagen with an IC50
      of 0.5-1.0 x 10(-6) M. These results, taken together, provide firm evidence that
      the major collagen-binding site in vWF resides in the A3 domain.

PMID- 7738020
TI  - Identification of the major site of apolipoprotein B modification by advanced
      glycosylation end products blocking uptake by the low density lipoprotein
      receptor.
AB  - Advanced glycosylation end products (AGEs) arise from glucose-derived Amadori
      products and have been implicated in the pathogenesis of diabetic vascular
      disease. We recently reported the presence of an AGE-modified form of low density
      lipoprotein (LDL) that circulates in high amounts in patients with diabetes or
      renal insufficiency and that exhibits impaired plasma clearance kinetics. We
      utilized AGE-specific antibodies to identify the major sites of AGE modification
      within protease-digested preparations of apolipoprotein B that impair the binding
      of the AGE-modified form of LDL by human fibroblast LDL receptors. The
      predominant site of AGE immunoreactivity was found to lie within a single, 67
      amino acid region located 1791 residues NH2-terminal of the putative LDL receptor
      binding domain. These data point to the high reactivity and specificity of this
      site for AGE formation and provide further evidence for important structural
      interactions between the LDL receptor binding domain and remote regions of the
      apolipoprotein B polypeptide.

PMID- 7738021
TI  - Cloning and functional expression of a thyrotropin receptor cDNA from rat fat
      cells.
AB  - Thyrotropin receptor (TSH-R) has been thought to be thyroid-specific, but, by
      Northern blot analysis, we found that rat adipose tissue expressed TSH-R mRNAs in
      amounts approaching those in the thyroid. To investigate the function of TSH-R
      from adipose tissue, we screened a rat fat cell lambda gt11 cDNA library for TSH
      R sequences using a 32P-labeled rat thyroid TSH-R cDNA as a probe. Among 10(6)
      plaques, we obtained four positive clones. Sequencing of these cDNAs has revealed
      that two of them (F alpha and F beta) contained both initiation and termination
      codons. Comparison of F alpha with the thyroid TSH-R cDNA sequence revealed that
      F alpha was almost identical to the thyroid TSH-R, except that nucleotides 1041
      and 1277 were changed from A to G and from C to T, respectively. In contrast, we
      found that F beta contained 21 novel nucleotides between nucleotides 467 and 468
      of the thyroid TSH-R cDNA, encoding an additional 7 amino acids. However, when we
      prepared mRNA from adipose tissue and transcribed it into cDNA, we failed to
      amplify the F beta type of TSH-R cDNA by polymerase chain reaction, suggesting
      that F beta mRNAs are rare in the tissue. We then ligated F cDNAs into pSG5 and
      transfected them with pSV2-neo into Chinese hamster ovary (CHO)-K1 cells. TSH
      stimulated cAMP formation in CHO-F alpha cells in a manner similar to that in CHO
      cells transfected with thyroid TSH-R cDNA. In contrast, no increase of cAMP was
      observed in CHO-F beta cells. IgG from patients with Graves' disease (n = 4)
      showed thyroid-stimulating antibody activity only in CHO-F alpha cells (1288
      4582%). In addition, CHO-F alpha cells and CHO cells transfected with thyroid TSH
      R showed similar 125I-TSH binding activity. These results indicate that the fat
      cell expresses high levels of a TSH-R whose function is indistinguishable from
      that in the thyroid and suggest that the TSH-R autoantibody plays an important
      role in the pathogenesis of the extrathyroidal manifestations of Graves' disease.

PMID- 7738022
TI  - Processing of the papain precursor. The ionization state of a conserved amino
      acid motif within the Pro region participates in the regulation of intramolecular
      processing.
AB  - The cysteine protease papain is synthesized as a 40-kDa inactive precursor with a
      107-amino-acid N-terminal pro region. Although sequence conservation in the pro
      region is lower than in the mature proteases, a conserved motif (Gly-Xaa-Asn-Xaa
      Phe-Xaa-Asp-36, papain precursor numbering) was found within the pro region of
      cysteine proteases of the papain superfamily. To determinate the function to this
      conserved motif, we have mutagenized at random each of the 4 residues
      individually within the pro region of the papain precursor. Precursor mutants
      were expressed in yeast, screened according to their ability to be processed
      through either a cis or trans reaction, into mature active papain. Three classes
      of mutants were found. Non-functional propapain mutants of the first class are
      completely degraded by subtilisin indicating that they are not folded into a
      native state. Mutants of the second class were neutral with respect to cis and
      trans processing. The third class included mutants that mostly accumulated as
      mature papain in the yeast vacuole. They had mutations that had lost the
      negatively charged Asp-36 residues and a mutation that probably introduces a
      positive charge, Phe-38His. The precursor of the Phe-38His mutant could be
      recovered by expression in a vph1 mutant yeast strain which has a vacuolar pH of
      about 7. The Phe-38His propapain mutant has an optimum pH of autoactivation about
      one pH unit higher than the wild type molecule. These results indicate that the
      electrostatic status of the conserved motif participates in the control of
      intramolecular processing of the papain precursor.

PMID- 7738024
TI  - Endothelin-induced endocytosis of cell surface ETA receptors. Endothelin remains
      intact and bound to the ETA receptor.
AB  - We demonstrate unusual features of the intracellular processing of endothelin-1
      (ET-1) and its receptor ETA, the receptor subtype that mediates contraction of
      vascular smooth muscle cells. First, we show that in stably transfected CHO cells
      expressing ETA, binding of an ET-1 ligand induces rapid endocytosis of cell
      surface ETA. Receptor endocytosis was measured both by immunofluorescence and by
      radioiodinated antibodies specific for ETA. Second, we demonstrate that ET-1
      remains intact for up to 2 h after endocytosis and, as judged by co
      immunoprecipitation, internalized 125I-ET-1 remains bound to ETA receptors. We
      hypothesize that internalized ET-1, bound to ETA receptors, continues to activate
      a signal-transducing G protein, thus accounting for the prolonged period of
      contraction induced in smooth muscle cells by a single administration of ET-1.

PMID- 7738023
TI  - Reconstitution of neuronal Cdc2-like kinase from bacteria-expressed Cdk5 and an
      active fragment of the brain-specific activator. Kinase activation in the absence
      of Cdk5 phosphorylation.
AB  - Neuronal Cdc2-like kinase is a heterodimer of Cdk5 and a 25-kDa subunit which is
      derived from a brain-specific 35-kDa novel protein, p35 (Lew, J., Huang, Q.-Q.,
      Qi, Z., Winkfein, R. J., Aebersold, R., Hunt, T., and Wang, J. H. (1994) Nature
      371, 423-426). Three truncated forms of p35 including the one corresponding to
      the 25-kDa subunit of the kinase have been expressed in Escherichia coli and
      shown to activate a bacteria-expressed Cdk5 with equal efficacy. The shortest
      truncated form of p35, p21, spanning amino acid residues 88 to 291, has been used
      to reconstitute active Cdk5 kinase and to characterize the activation reaction.
      The purified kinase displays similar specific enzyme activity and similar
      phosphorylation site specificity as the neuronal Cdc2-like kinase purified from
      bovine brain. Bovine brain extract contains Cdk5 uncomplexed with p35 or p25
      which has also been found to be activated by p21 or p25. The results substantiate
      the previous suggestion that p35 is a specific Cdk5 activator. Several
      observations suggest that, unlike other well characterized Cdc2-like kinases
      whose activities depend on the phosphorylation of the catalytic subunits at a
      specific site by a distinct kinase, the reconstituted Cdk5/p21 does not depend on
      the phosphorylation of Cdk5 for activity. The reconstitution of the highly active
      Cdk5 kinase was achieved without requiring any other kinase in the reconstitution
      reaction. The possibility of autophosphorylation of Cdk5 on the putative
      activation site has been ruled out as no phosphorylation occurred on Cdk5 during
      the enzyme reaction. The rate and extent of the kinase reconstitution were not
      significantly affected by Mg2+ ATP.

PMID- 7738026
TI  - Cloning of the mouse class IV alcohol dehydrogenase (retinol dehydrogenase) cDNA
      and tissue-specific expression patterns of the murine ADH gene family.
AB  - Humans possess five classes of alcohol dehydrogenase (ADH), including forms able
      to oxidize ethanol or formaldehyde as part of a defense mechanism, as well as
      forms acting as retinol dehydrogenases in the synthesis of the regulatory ligand
      retinoic acid. However, the mouse has previously been shown to possess only three
      forms of ADH. Hybridization analysis of mouse genomic DNA using cDNA probes
      specific for each of the five classes of human ADH has now indicated that mouse
      DNA cross-hybridizes to only classes I, III, and IV. With human class II or class
      V ADH cDNA probes, hybridization to mouse genomic DNA was very weak or
      undetectable, suggesting either a lack of these genes in the mouse or a high
      degree of mutational divergence relative to the human genes. cDNAs for murine ADH
      classes I and III have previously been cloned, and we now report the cloning of a
      full-length mouse class IV ADH cDNA. In Northern blot analyses, mouse class IV
      ADH mRNA was abundant in the stomach, eye, skin, and ovary, thus correlating with
      the expression pattern for the mouse Adh-3 gene previously determined by enzyme
      analysis. In situ hybridization studies on mouse stomach indicated that class IV
      ADH transcripts were abundant in the mucosal epithelium but absent from the
      muscular layer. Comparison of the expression patterns for all three mouse ADH
      genes indicated that class III was expressed ubiquitously, whereas classes I and
      IV were differentially expressed in an overlapping set of tissues that all
      contain a large component of epithelial cells. This expression pattern is
      consistent with the ability of classes I and IV to oxidize retinol for the
      synthesis of retinoic acid known to regulate epithelial cell differentiation. The
      results presented here indicate that the mouse has a simpler ADH gene family than
      the human but has conserved class IV ADH previously shown to be a very active
      retinol dehydrogenase in humans.

PMID- 7738027
TI  - WT1-mediated transcriptional activation is inhibited by dominant negative mutant
      proteins.
AB  - The WT1 tumor suppressor gene encodes four isoforms of a zinc finger
      transcription factor with both activation and repression functions which are
      dependent upon promoter architecture. Using a simple HSV-tk promoter containing
      5'-Egr-1/WT1-binding sites, we found that WT1 isoforms (A) and (B) strongly
      activated transcription. WT1(A) and (B) bound equally well to the Egr-1/WT1
      binding site, but WT1(B), which contains a 17 amino acid insertion compared to
      WT1(A), was a consistently stronger activator of transcription than WT1(A).
      Transcriptional activation by wild-type WT1 was inhibited by coexpression of
      WT(PM) or WT(AR), genetically defined dominant negative alleles of WT1. In vitro,
      as well as in the yeast two-hybrid system, WT1 protein associated with itself and
      with dominant negative mutant proteins. The major domain required for self
      association and inhibition of transcriptional activation mapped to the first 182
      amino acids of WT1. Dominant negative WT1 alleles may play a role in
      tumorigenesis by associating with wild-type WT1 proteins and decreasing their
      transcriptional activity.

PMID- 7738025
TI  - Complementation of Saccharomyces cerevisiae strains containing fatty acid
      activation gene (FAA) deletions with a mammalian acyl-CoA synthetase.
AB  - Four unlinked fatty acid activation (FAA) genes encoding acyl-CoA synthetases
      have been identified in Saccharomyces cerevisiae and characterized by noting the
      phenotypes of isogenic strains containing all possible combinations of faa null
      alleles. None of these genes is required for vegetative growth when acyl-CoA
      production by the fatty acid synthetase (Fas) complex is active. When Fas is
      inhibited by cerulenin, exponentially growing cells are not viable on media
      containing a fermentable carbon source unless supplemented with fatty acids such
      as myristate, palmitate, or oleate. The functionally interchangeable FAA1 and
      FAA4 genes are responsible for activation of these imported fatty acids. Analysis
      of lysates prepared from isogenic FAA1FAA4 and faa1 delta faa4 delta strains
      indicated that Faa1p and Faa4p together account for 99% of total cellular
      myristoyl-CoA and palmitoyl-CoA synthetase activities. Genetic complementation
      studies revealed that rat liver acyl-CoA synthetase (RLACS) rescues the viability
      of faa1 delta faa4 delta cells in media containing a fermentable carbon source,
      myristate or palmitate, plus cerulenin. Rescue is greater at 37 degrees C
      compared with 24 degrees C, paralleling the temperature-dependent changes in
      RLACS activity in vitro as well as the enzyme's ability to direct incorporation
      of tritiated myristate and palmitate into cellular phospholipids in vivo.
      Complementation by RLACS is blocked by treatment of cells with triacsin C (1
      hydroxy-3-(E,E,E,2',4',7'- undecatrienylidine)triazene). Even though Faa1p,
      Faa4p, and RLACS are all able to activate imported myristate and palmitate in S.
      cerevisiae, the sensitivity of Faa4p and RLACS, but not Faa1p, to inhibition by
      triacsin C suggests that the rat liver enzyme is functionally more analogous to
      Faa4p than to Faa1p. Finally, an assessment of myristate and palmitate import
      into FAA1FAA4 and faa1 delta faa4 delta strains, with or without episomes that
      direct overexpression of Faa1p, Faa4p or RLACS, indicated that fatty acid uptake
      is not coupled to activation in S. cerevisiae.

PMID- 7738029
TI  - Antioxidant role of Rhodnius prolixus heme-binding protein. Protection against
      heme-induced lipid peroxidation.
AB  - Heme in aqueous solutions actively promotes free radical reactions leading to
      degradation of biological molecules. The blood-sucking insect Rhodnius prolixus
      has a heme-binding protein (RHBP) in its hemolymph (Oliveira, P.L., Kawooya,
      J.K., Ribeiro, J.M.C., Meyer, T., Poorman, R., Alves, E.W., Walker, F., Padovan,
      G.J., and Masuda, H. (1994) J. Biol. Chem. 270, 10897-10901. Here we show that
      this protein inhibits heme-dependent peroxidation of both linolenic acid
      liposomes and lipophorin, the main lipoprotein of insect hemolymph. The oxidized
      lipophorin is functionally impaired, being defective both in its capacity to be
      loaded with phospholipids from the fat body as well as in its ability to deliver
      phospholipids to the growing oocytes. RHBP prevents the heme-induced oxidative
      damage to lipophorin. It is proposed that in vivo RHBP binds the heme derived
      from digestion of blood hemoglobin, suppressing the generation of activated
      oxygen species and protecting the insect against oxidative stress throughout the
      feeding cycle.

PMID- 7738030
TI  - A heme-binding protein from hemolymph and oocytes of the blood-sucking insect,
      Rhodnius prolixus. Isolation and characterization.
AB  - A heme-binding protein has been isolated and characterized from both the
      hemolymph and oocytes of the blood-sucking insect, Rhodnius prolixus. The protein
      from both sources is identical in most aspects studied. The Rhodnius heme-binding
      protein (RHBP) is composed of a single 15-kDa polypeptide chain coiled in a
      highly alpha-helical structure which binds non-covalently one heme/polypeptide
      chain. This RHBP is not produced by limited degradation of hemoglobin from the
      vertebrate host, since specific polyclonal antibodies against it do not cross
      react with rabbit hemoglobin, and since it differs from hemoglobin in having a
      distinct amino-acid composition and NH2-terminal sequence. The spectrum of the
      dithionite-reduced protein has peaks at 426, 530, and 559 nm and resembles that
      of a b-type cytochrome. RHBP from hemolymph is not saturated with heme and
      promptly binds heme added to the solution. The oocyte protein, on the other hand,
      is fully saturated and is not capable of binding additional heme.

PMID- 7738028
TI  - Mechanisms of enhanced transmembrane signaling by an insulin receptor lacking a
      cytoplasmic beta-subunit domain.
AB  - We have recently characterized a mutant insulin receptor (HIR delta 978) in which
      the insulin receptor beta-subunit was truncated at amino acid residue 978.
      Compared with parental Rat1 cells, the cells expressing the truncated receptor
      exhibited enhanced sensitivity to insulin's biologic actions. All of these
      effects are now extended to transcriptional events, since we now show enhanced
      sensitivity to insulin stimulation of c-fos mRNA expression. These effects were
      insulin-specific, since insulin-like growth factor-1 stimulation of glucose
      incorporation into glycogen, alpha-aminoisobutyric acid uptake, and thymidine
      incorporation into DNA were normal. In addition, the truncated receptor exhibited
      enhanced sensitivity only in vivo, but not in vitro, since the kinase activity of
      wheat germ agglutinin-purified receptor preparations was comparable between HIR
      delta 978 and parental Rat1 insulin receptors. Parental rat endogenous insulin
      like growth factor-1 receptors and transfected human insulin receptors form
      hybrid receptors as well as homologous tetrameric receptors. The normal
      heterotetrameric receptors possess kinase activity in vivo leading to tyrosine
      phosphorylation of insulin receptor substrate-1 (IRS-1) and its association with
      the p85 regulatory subunit of phosphatidyl inositol 3-kinase. Interestingly,
      preincubation with human-specific anti-insulin receptor antibody abolished the
      increased insulin sensitivity in glucose incorporation into glycogen in HIR delta
      978 cells. Furthermore, microinjection of anti-IRS-1 antibody into HIR delta 978
      cells inhibited insulin stimulation of DNA synthesis. In summary: 1) truncated
      receptors on the cell surface confer enhanced insulin sensitivity in vivo; 2) the
      normal heterotetrameric receptors are functionally active and couple to IRS-1
      efficiently; and 3) IRS-1 is an important molecule transmitting insulin's
      biological signals in HIR delta 978 cells.

PMID- 7738031
TI  - Different intracellular locations for prostaglandin endoperoxide H synthase-1 and
      -2.
AB  - The subcellular locations of prostaglandin endoperoxide synthase-1 and -2 (PGHS-1
      and -2) were determined by quantitative confocal fluorescence imaging microscopy
      in murine 3T3 cells and human and bovine endothelial cells using
      immunocytofluorescence with isozyme-specific antibodies. In all of the cell types
      examined, PGHS-1 immunoreactivity was found equally distributed in the
      endoplasmic reticulum (ER) and nuclear envelope (NE). PGHS-2 immunoreactivity was
      also present in the ER and NE. However, PGHS-2 staining was twice as concentrated
      in the NE as in the ER. A histofluorescence staining method was developed to
      localize cyclooxygenase/peroxidase activity. In quiescent 3T3 cells, which
      express only PGHS-1, histofluorescent staining was most concentrated in the
      perinuclear cytoplasmic region. In contrast, histochemical staining for PGHS-2
      activity was about equally intense in the nucleus and in the cytoplasm, a pattern
      of activity staining distinct from that observed with PGHS-1. Our results
      indicate that there are significant differences in the subcellular locations of
      PGHS-1 and PGHS-2. It appears that PGHS-1 functions predominantly in the ER
      whereas PGHS-2 may function in the ER and the NE. We speculate that PGHS-1 and
      PGHS-2 acting in the ER and PGHS-2 functioning in the NE represent independent
      prostanoid biosynthetic systems.

PMID- 7738032
TI  - Calpains are activated in necrotic fibers from mdx dystrophic mice.
AB  - Death of dystrophin-deficient muscle purportedly results from increases in [Ca]in
      that cause the activation of calpains. We have tested whether calpains play a
      role in this process by assaying for changes in calpain concentration and
      activation in peak necrotic mdx mice (4 weeks of age) and in completely
      regenerated mdx mice (14 weeks of age). Biochemical fractionation and
      immunoblotting with epitope-specific antisera allowed measurement of the
      concentrations of m- and mu-calpains and the extent of autoproteolytic
      modification. Our findings show that total calpain concentration is elevated in
      both 4-week and 14-week mdx mice. This increase in concentration was shown to
      result primarily from a significant increase in m-calpain concentration at 4
      weeks. Northern analysis demonstrated that neither m- nor mu-calpain mRNA
      concentrations differed between mdx and controls suggesting that the increased
      calpain concentration results from post-translational regulation. Immunoblotting
      with antibodies directed against amino-terminal peptides revealed an increase in
      autoproteolysis of mu-calpain, indicative of increased activation. The extent of
      autoproteolysis of mu-calpain returns to control levels during regeneration. This
      is not a consequence of increased calpastatin mRNA or protein. The findings
      reported here support a role for calpains in both the degenerative and
      regenerative aspects of mdx dystrophy.

PMID- 7738034
TI  - Identification, characterization, and intracellular distribution of cofilin in
      Dictyostelium discoideum.
AB  - We identified and purified an actin monomer-binding protein of apparent molecular
      weight of 15,000 from Dictyostelium discoideum. The 15-kDa protein depolymerized
      actin filaments in a pH-dependent manner. The protein also had an activity to
      decrease apparent viscosity of actin solutions in a dose-dependent manner. This
      activity was inhibited by phosphatidyl inositides. Molecular cloning of genes
      encoding this protein revealed that the protein is 42% identical in its primary
      sequence to yeast cofilin. We concluded that the 15-kDa protein is cofilin of
      this organism. D. discoideum cells contain two cofilin genes (DCOF1 and DCOF2)
      whose nucleotide sequences were entirely identical in their exsons while the
      promoter and intron regions were different. Promoter assay experiments revealed
      that DCOF1 is expressed both in vegetative and differentiating cells and that
      DCOF2 is not expressed under any conditions examined. Gene disruption experiments
      suggested that DCOF1 might be essential for the proliferation of D. discoideum
      cells whereas the disruption of DCOF2 was proven not to alter any phenotypes.
      Indirect immunofluorescence microscopic observations showed that cofilin is
      distributed diffusely throughout cytoplasm in vegetative cells. In flattened
      cells under starvation stress, cofilin localized at dramatically reorganizing
      actin-cytoskeletons in ruffling membranes of the leading edge, but not at rigid
      actin meshwork in focal adhesion plaques. These results suggest that cofilin may
      be involved in dynamic reorganization of membranous actin cytoskeletons.

PMID- 7738033
TI  - Cardiotrophin-1. Biological activities and binding to the leukemia inhibitory
      factor receptor/gp130 signaling complex.
AB  - Cardiotrophin-1 (CT-1) is a newly isolated cytokine that was identified based on
      its ability to induce cardiac myocyte hypertrophy. It is a member of the family
      of cytokines that includes interleukins-6 and -11, leukemia inhibitory factor
      (LIF), ciliary neurotrophic factor, and oncostatin M. These cytokines induce a
      pleiotropic set of growth and differentiation activities via receptors that use a
      common signaling subunit, gp130. In this work we determine the activity of CT-1
      in six in vitro biological assays and examine the composition of its cell surface
      receptor. We find that CT-1 is inactive in stimulating the growth of the
      hybridoma cell line, B9 and inhibits the growth of the mouse myeloid leukemia
      cell line, M1. CT-1 induces a phenotypic switch in rat sympathetic neurons and
      promotes the survival of rat dopaminergic and chick ciliary neurons. CT-1 also
      inhibits the differentiation of mouse embryonic stem cells. CT-1 and LIF cross
      compete for binding to M1 cells, Kd [CT-1] approximately 0.7 nM, and this binding
      is inhibited by an anti-gp130 monoclonal antibody. Both ligands can be
      specifically cross-linked to a protein on M1 cells with the mobility of the LIF
      receptor (approximately 200 kDa). In addition, CT-1 binds directly to a purified,
      soluble form of the LIF receptor in solution (Kd approximately 2 nM). These data
      show that CT-1 has a wide range of hematopoietic, neuronal, and developmental
      activities and that it can act via the LIF receptor and the gp130 signaling
      subunit.

PMID- 7738035
TI  - Clathrin binding and assembly activities of expressed domains of the synapse
      specific clathrin assembly protein AP-3.
AB  - We separately expressed the 58-kDa C-terminal, 42-kDa middle, 16-kDa C-terminal,
      and 33-kDa N-terminal regions of AP-3 (also called F1-20, AP180, NP185, and
      pp155), and determined their clathrin binding and assembly properties. The 58-kDa
      C-terminal region of AP-3 is able to bind to clathrin triskelia and assemble them
      into a homogeneous population of clathrin cages and will also bind to
      preassembled clathrin cages. The 42-kDa central region of AP-3 can bind to both
      clathrin triskelia and to clathrin cages, but cannot assemble clathrin triskelia
      into clathrin cages. The 16-kDa C-terminal region of AP-3 can bind to clathrin
      cages, but cannot bind to clathrin triskelia or assemble clathrin triskelia into
      clathrin cages. The clathrin binding activities of the 42-kDa central region and
      16-kDa C-terminal region are weaker than the corresponding activity of either the
      58-kDa C-terminal region or full-length AP-3. Previous efforts had mapped a
      clathrin binding site within the N-terminal 33 kDa of AP-3 (Murphy, J. E.,
      Pleasure, I. T., Puszkin, S., Prasad, K., and Keen, J. H. (1991) J. Biol. Chem.
      266, 4401-4408; Morris, S. A., Schroder, S., Plessmann, U., Weber, K., and
      Ungewickell, E. (1993) EMBO J. 12, 667-675). However, although the N-terminal 33
      kDa of AP-3 is able to bind to clathrin triskelia (Murphy, J. E., Pleasure, I.
      T., Puszkin, S., Prasad, K., and Keen, J. H. (1991) J. Biol. Chem. 266, 4401
      4408; Ye, W., and Lafer, E. M. (1995) J. Neurosci. Res. 41, 15-26), it does not
      promote their assembly into clathrin cages (Murphy, J. E., Pleasure, I. T.,
      Puszkin, S., Prasad, K., and Keen, J. H. (1991) J. Biol. CHem. 266, 4401-4408;
      Ye, W., and Lafer, E. M. (1995) J. Neurosci. Res. 41, 15-26) or bind to
      preassembled clathrin cages (Ye, W., and Lafer, E. M. (1995) J. Neurosci. Res.
      41, 15-26). It appears that the smallest functional unit that carries out all of
      the reported clathrin binding and assembly properties of AP-3, essentially as
      well as the full-length protein, is the 58-kDa C-terminal region.

PMID- 7738036
TI  - PER3, a gene required for peroxisome biogenesis in Pichia pastoris, encodes a
      peroxisomal membrane protein involved in protein import.
AB  - PER genes are essential for the biogenesis of peroxisomes in the yeast Pichia
      pastoris. Here we describe the cloning of PER3 and functional characterization of
      its product Per3p. The PER3 sequence predicts that Per3p is a 713-amino acid (81
      kDa) hydrophobic protein with at least three potential membrane-spanning domains.
      We show that Per3p is a membrane protein of the peroxisome. Methanol- or oleate
      induced cells of per3-1, a mutant strain generated by chemical mutagenesis, lack
      normal peroxisomes but contain numerous abnormal vesicular structures. The
      vesicles contain thiolase, a PTS2 protein, but only a small portion of several
      other peroxisomal enzymes, including heterologously expressed luciferase, a PTS1
      protein. These results suggest that the vesicles in per3-1 cells are peroxisomal
      remnants similar to those observed in cells of patients with the peroxisomal
      disorder Zellweger syndrome, and that the mutant is deficient in PTS1 but not
      PTS2 import. In a strain in which most of PER3 was deleted, peroxisomes as well
      as peroxisomal remnants appeared to be completely absent, and both PTS1- and PTS2
      containing enzymes were located in the cytosol. We propose that Per3p is an
      essential component of the machinery required for import of all peroxisomal
      matrix proteins and is composed of independent domains involved in the import of
      specific PTS groups.

PMID- 7738037
TI  - Long term phorbol ester treatment down-regulates the beta 3-adrenergic receptor
      in 3T3-F442A adipocytes.
AB  - The role of protein kinase C (PKC) in the regulation of the beta 3-adrenergic
      receptor (beta 3-AR) gene was examined in murine 3T3-F442A adipocytes, which
      express this receptor subtype at a high level. We also investigated the
      involvement of this kinase in the modulation of beta 3-AR gene expression by
      insulin. Long term exposure of 3T3-F442A adipocytes to phorbol 12-myristate 13
      acetate (PMA) decreased beta 3-AR mRNA content in a time- and concentration
      dependent manner, with maximal changes observed at 6 h (6.5-fold decrease) and at
      100 nM PMA. This inhibition was selective for beta 3-AR transcripts, since beta 1
      and beta 2-AR mRNA content remained unchanged. Also, (-)-[125I]cyanopindolol
      saturation and competition binding experiments on adipocyte membranes indicated
      that PMA induced an approximately 2-fold decrease in beta 3-AR expression, while
      that of the two other subtypes was not affected. This correlated with a lower
      efficacy of beta 3-AR agonists to stimulate adenylyl cyclase. Conversely, long
      term exposure to PMA did not alter adenylyl cyclase activity in response to
      guanosine 5'-O-(3-thiotriphosphate) or forskolin. The inactive phorbol ester 4
      alpha-phorbol 12,13-didecanoate did not repress beta 3-AR mRNA levels. Inhibition
      of beta 3-AR mRNA by PMA was suppressed by the PKC-selective inhibitor
      bisindolylmaleimide, and was not observed in PKC-depleted cells, indicating that
      PKC was involved in this response. mRNA turnover experiments showed that the half
      life of beta 3-AR transcripts was not affected by long term PMA exposure. When
      3T3-F442A adipocytes were pretreated with PMA for 24 h to down-regulate PKC, or
      with bisindolylmaleimide, the insulin-induced inhibition of beta 3-AR mRNA levels
      was reduced by 44-67%. These findings demonstrate that sustained PKC activation
      exerts a specific control of beta 3-AR gene expression and is involved, at least
      in part, in the modulation by insulin of this adrenergic receptor subtype.

PMID- 7738038
TI  - The androgen receptor is transcriptionally suppressed by proteins that bind
      single-stranded DNA.
AB  - The androgen receptor (AR) is a nuclear transcription factor that is essential
      for development of the male urogenital tract. In the current work, we have
      characterized the mouse androgen receptor suppressor (mARS). A single, 20-base
      pair, region (TCCCCCCACCCACCCCC-CCT) was sufficient for suppression in
      chloramphenicol acetyltransferase assays. Northern analysis indicated that
      translational regulation is not necessary for the suppression. Analysis of the AR
      mRNA half-life indicated that the mARS does not affect AR RNA degradation. Gel
      mobility assays showed that the mARS is bound by multiple proteins that can
      recognize single-stranded DNA and RNA. In addition, differing proteins are
      expressed in distinct tissues. Purification of some of these proteins has shown
      that a doublet of 33 and 35 kDa binds to the G-rich strand and that a 52-kDa
      protein binds to the C-rich strand. Southwestern blots have confirmed that these
      proteins are indeed recognized by the mARS. The results of these experiments
      indicate that the AR 5'-untranslated region contains a suppressor element that
      can be bound by multiple proteins. The mARS appears to be acting either by
      altering transcription initiation or blocking transcription elongation.
      Characterization of this suppressor may provide insight into the physiological
      means by which the AR is regulated.

PMID- 7738039
TI  - TATA-binding protein residues implicated in a functional interplay between
      negative cofactor NC2 (Dr1) and general factors TFIIA and TFIIB.
AB  - The TATA-binding protein (TBP) plays a key role in transcription initiation.
      Several negative cofactors (NC1, NC2, and Dr1) are known to interact with TBP in
      a manner that prevents productive interactions of transcription factors TFIIA and
      TFIIB with promoter-bound TBP. To gain insights into the regulatory interplay on
      the surface of TBP, we have employed mutant forms of TBP to identify amino acid
      residues important for interactions with the negative regulatory cofactor NC2 and
      the general factor TFIIB. The results show the involvement of distinct domains of
      TBP in these interactions. Residues (Lys-133, Lys-145, and Lys-151) in the basic
      repeat region are important for interactions with NC2, as well as with TFIIA
      (Buratowski, S., and Zhou, H. (1992) Science 255, 1130-1132; Lee, D. K., DeJong,
      J., Hashimoto, S., Horikoshi, M., and Roeder, R. G. (1992) Mol. Cell. Biol. 12,
      5189-5196), whereas a residue (Leu-189) in the second stirrup-like loop spanning
      S2' and S3' is required for interaction with TFIIB. In addition, we demonstrate
      that NC2 is identical to the previously cloned negative cofactor Dr1. The
      implications of these results for TBP structure and function are discussed.

PMID- 7738040
TI  - The Ras-related GTP-binding protein, Rab1B, regulates early steps in exocytic
      transport and processing of beta-amyloid precursor protein.
AB  - The role of the Ras-related GTP-binding protein, Rab1B, in intracellular
      trafficking of beta-amyloid precursor protein (beta APP) was studied in cultured
      293 cells. beta APP is processed via one of two alternative routes. In the major
      secretory pathway, beta APP is cleaved by alpha-secretase within the region
      comprising the beta-amyloid peptide (A beta), resulting in release of a soluble
      NH2-terminal exodomain (APP alpha) and a 3-kDa peptide (p3) derived from the
      carboxyl-terminal tail. In the alternative amyloidogenic pathway, beta APP is
      cleaved by beta-secretase, with the release of a truncated exodomain (APP beta)
      and an intact A beta peptide. When beta APP751 was coexpressed with Rab1B(wt) or
      dominant-negative Rab1B mutants (Rab1BN121I or Rab1BS22N) there was a marked
      decrease in conversion of the immature Endo-H sensitive form of beta APP751 (108
      kDa) to the mature O-glycosylated form of beta APP751 (130 kDa) in cells
      expressing the mutant forms of Rab1B. The block in Golgi-dependent processing of
      beta APP was accompanied by inhibition of secretion of APPS (APP alpha). A
      similar decrease in secretion of APPS (APP alpha+APP beta) was observed in cells
      that were coexpressing Rab1BN121I with the "Swedish" variant of beta APP751 (i.e.
      beta APPSW751), which undergoes increased amyloidogenic processing. Coincident
      with the decline in APPS secretion, the cells coexpressing beta APPSW751 with
      Rab1BN121I showed a 90% decrease in A beta secretion. The data indicate that
      Rab1B plays a key role in endoplasmic reticulum-->Golgi transport of beta APP,
      and that beta APP must pass through a late Golgi compartment before entering
      either the alpha-secretase or the amyloidogenic beta-secretase pathway. The
      results also suggest that mutant versions of other Rab proteins that function in
      different parts of the exocytic and endocytic pathways may be useful in defining
      the specific routes of beta APP transport involved in the biogenesis of A beta.

PMID- 7738041
TI  - A regulatory role for sphingolipids in neuronal growth. Inhibition of
      sphingolipid synthesis and degradation have opposite effects on axonal branching.
AB  - Sphingolipids, particularly gangliosides, are enriched in neuronal membranes
      where they have been implicated as mediators of various regulatory events. We
      recently provided evidence that sphingolipid synthesis is necessary to maintain
      neuronal growth by demonstrating that in hippocampal neurons, inhibition of
      ceramide synthesis by Fumonisin B1 (FB1) disrupted axonal outgrowth (Harel, R.
      and Futerman, A. H. (1993) J. Biol. Chem. 268, 14476-14481). We now analyze
      further the relationship between neuronal growth and sphingolipid metabolism by
      examining the effect of an inhibitor of glucosylceramide synthesis, D-threo-1
      phenyl-2-decanoylamino-3-morpholino-1- propanol (PDMP) and by examining the
      effects of both FB1 and PDMP at various stages of neuronal development. No
      effects of FB1 or PDMP were observed during the first 2 days in culture, but by
      day 3 axonal morphology was significantly altered, irrespective of the time of
      addition of the inhibitors to the cultures. Cells incubated with FB1 or PDMP had
      a shorter axon plexus and less axonal branches. FB1 appeared to cause a
      retraction of axonal branches between days 2 and 3, although long term incubation
      had no apparent effect on neuronal morphology or on the segregation of axonal or
      dendritic proteins. In contrast, incubation of neurons with conduritol B-epoxide,
      an inhibitor of glucosylceramide degradation, caused an increase in the number of
      axonal branches and a corresponding increase in the length of the axon plexus. A
      direct correlation was observed between the number of axonal branch points per
      cell and the extent of inhibition of either sphingolipid synthesis or
      degradation. These results suggest that sphingolipids play an important role in
      the formation or stabilization of axonal branches.

PMID- 7738042
TI  - Newly synthesized transferrin receptors can be detected in the endosome before
      they appear on the cell surface.
AB  - It is well established that a proportion of newly synthesized lysosomal enzymes
      and class II major histocompatibility complex antigens are delivered directly to
      the endocytic pathway from the Golgi complex. Here we show that a significant
      proportion of newly synthesized transferrin receptors can be detected in
      endosomes before reaching the cell surface. These newly synthesized transferrin
      receptors are delivered to the endosome more efficiently than either
      constitutively secreted soluble proteins or glycophosphatidylinositol-anchored
      plasma membrane proteins suggesting that their transfer to the endosome is signal
      dependent. Identification of a signal-dependent transfer step for proteins like
      the transferrin receptor operating on the exocytic pathway has important
      implications for membrane biogenesis, especially in the establishment of cell
      surface polarity.

PMID- 7738044
TI  - Characteristics of the alpha 2/beta 2-adrenergic receptor-coupled adenylyl
      cyclase system in rat myometrium during pregnancy.
AB  - alpha 2A- and alpha 2B-adrenoreceptors (AR), identified by Northern blotting in
      rat myometrium, showed a differential expression during the course of pregnancy.
      Indeed, the alpha 2A-AR transcript was present at mid-pregnancy, whereas high
      levels of alpha 2B-AR mRNA could be detected at term. The role of these subtypes
      in modulating beta 2-AR-stimulated adenylyl cyclase activity was investigated on
      myometrial membranes from mid-pregnancy and term. At nanomolar concentrations of
      clonidine (full alpha 2-AR agonist) or oxymetazoline (partial alpha 2A-AR
      agonist), adenylyl cyclase activity was inhibited by up to 50 +/- 7% at mid
      pregnancy or 75 +/- 7% at term, whereas at micromolar concentrations, alpha 2-AR
      agonists potentiate adenylyl cyclase activity by 140-170% at mid-pregnancy. Both
      inhibitory and stimulatory components of this biphasic response were blocked by
      yohimbine, a selective alpha 2-AR antagonist. Preincubation of myometrial
      membranes with Gi2 and/or Gi3 antisera eliminated alpha 2-AR mediated attenuation
      or potentiation of isoproterenol-stimulated adenylyl cyclase, thus indicating
      that both the inhibitory and stimulatory components are mediated via Gi2 and Gi3.
      In addition, type II and IV adenylyl cyclases were identified by Northern
      blotting in the pregnant rat myometrium. Altogether these data strongly suggest
      that the alpha 2A-AR at mid-pregnancy potentiates adenylyl cyclase types II and
      IV through beta gamma released from Gi2 and Gi3 proteins, whereas the alpha 2B-AR
      expression at term may be related to persistent inhibition.

PMID- 7738045
TI  - Dynamic behavior of a biphasic cartilage model under cyclic compressive loading.
AB  - It is well known that dynamic mechanical loads can stimulate the biosynthetic
      activity of articular cartilage. Studying the mechanical environment of
      chondrocytes under dynamic loading conditions can help to explain this mechano
      biological phenomenon in articular cartilage. In this study, the linear biphasic
      theory was used to examine the dynamic mechanical behavior of articular cartilage
      under a cyclic compressive force. We first studied the dynamic confined
      compression of a cartilage disk as a simplified one-dimensional model and then
      investigated the role of the relatively impermeable subchondral bone structure on
      the dynamic behavior of the cartilage extracellular matrix (ECM). Under an
      assumption of articular cartilage as a biphasic composite structure of a porous
      elastic solid matrix and interstitial fluid, the porous ECM of the articular
      cartilage was repeatedly compressed and expanded during the loading-unloading
      phases of the cyclic compressive force. One interesting finding of this study was
      the oscillating positive (supra-ambient)-negative (sub-ambient) hydrostatic
      pressure within the cartilage ECM under cyclic compressive loading. The pattern
      of the dynamic behavior of the cartilage ECM strongly depended on the loading
      frequency and the primary diffusion characteristic time, tau d. This finding is
      consistent with those of previous studies (Guilak et al., 1990 Adv Biomech. ASME,
      225-228; Mow et al., 1990, Biomechanics of Diarthrodial Joints, pp. 215-260.

PMID- 7738043
TI  - Sequence and spatial requirements for regulated muscle-specific processing of the
      sarco/endoplasmic reticulum Ca(2+)-ATPase 2 gene transcript.
AB  - Expression of the muscle-specific 2a isoform of the sarco/endoplasmic reticulum
      Ca2+ ATPase (SERCA2) requires activation of an otherwise inefficient splicing
      process at the 3'-end of the primary gene transcript. The sequence and topology
      requirements for this regulated splicing event were studied in the BC3H1 myogenic
      cell line using a minigene containing the 3'-end of the SERCA2 gene. In
      undifferentiated BC3H1 cells, the splice process is made inefficient by the
      presence of a weak muscle-type 5'-donor site (5'D1) and a long terminal intron.
      Both optimizing the 5'D1 and decreasing the length of the muscle-specific intron,
      induced muscle-type splicing in undifferentiated myogenic cells. Moreover, the
      induction of muscle-type transcripts was only observed when two competing
      processing sites, the polyadenylation site (pAu) used in non-muscle cells and the
      second neuronal 5'-donor site (5'D2), were weak. Indeed, making 5'D2 consensus
      induced neuronal-type splicing in undifferentiated myocytes and prevented the
      appearance of muscle-type transcripts. Similarly, replacing the polyadenylation
      site (pAu) with a strong site almost completely inhibited muscle-type splicing
      after myogenic differentiation. We conclude that weak processing sites and a long
      terminal intron are required for tissue-dependent mRNA processing of the SERCA2
      transcript.

PMID- 7738046
TI  - The effect of rider weight on rider-induced loads during common cycling
      situations.
AB  - Motivated by the desire to provide information useful in the design analysis of
      bicycle frames, the hypothesis tested was that a simple linear model would relate
      the maximum magnitudes of rider-induced loads to rider weight. Rider-induced
      loads are loads developed as a result of weight and muscular actions during
      pedalling. To test this hypothesis, five riders spanning a wide weight range rode
      a bicycle unrestrained on a treadmill. Dynamometers measured six components of
      pedal loads and five components of both seat and handlebar loads while riders
      rode three common cycling situations--seated cruising, seated climbing, and
      standing climbing. Average, average maximum, and average minimum values were
      computed for all load components and each was analyzed statistically. For all
      three test cases, the regression slope was significant for the force component
      normal to the pedal surface. Because the normal pedal force component has been
      shown previously to dominate frame stress at the point most likely to fatigue
      (Hull and Bolourchi, 1988, J. Strain. Anal. 23, 105-114), the results of this
      study should be useful in designing frames optimized for minimum weight and
      acceptable structural reliability.

PMID- 7738047
TI  - Predicting the kinematics and kinetics of gait based on the optimum trajectory of
      the swing limb.
AB  - An algorithm was developed to predict the minimum energy consumption trajectory
      of the swing limb. The method of dynamic programming, a multistage optimization
      method, was applied to generate the optimum trajectory of the swing ankle which
      minimized the mechanical energy required to generate the moments of the joints of
      the lower extremities during the single support phase of gait. Predictions and
      measurements of gait were compared for six healthy subjects. The predicted hip
      and knee flexion angles of the swing limb were not significantly different from
      those experimentally measured except for hip flexion at times greater than 75% of
      the swing period. The predicted ground reaction forces were not significantly
      different from the measured ground reaction forces. Furthermore, the moments
      about the joints were not significantly different from those computed using the
      measured ground reaction forces and kinematics of the limbs. The results of this
      study support the hypothesis that human gait is energy efficient.

PMID- 7738048
TI  - Hemodynamics of an artery with mild stenosis.
AB  - In this study the hemodynamics in the early stages of the atherosclerotic process
      -when a neointimal hyperplasia or an intimal fibrocellular hypertrophy takes
      place--is theoretically investigated. A local, slight increase in the wall
      thickness of a canine femoral artery is simulated using an original two
      dimensional mathematical model of arterial hemodynamics and the effects induced
      on the velocity field by the simulated mild stenosis--only 2% of area reduction-
      are analysed. The model incorporates: fluid non-linear inertial forces,
      viscoelastic wall motion, anatomical taper, unsteady flow, pressure propagation
      and reflections on both the proximal and distal vessel ends. Two different
      physiological pulsatile flows are considered: a basal flow condition and a light
      vasodilation state inducing in the vessel segment a limited increase in mean flow
      (50%). The distribution along the vessel during the cardiac cycle of both the
      velocity profile and wall shear stress, are shown. The shape of velocity
      distributions is strongly perturbed by the stenosis and disturbances are clearly
      evident whatever instant of the cardiac cycle is considered. After
      vasodilatation, during the phase of systolic deceleration, a vortex circulation
      appears in the post-stenotic region. The vortex persists for the whole diastolic
      phase, causing a very strong stress at the arterial wall: wall shear stress in
      the distal part of the simulated mild stenosis is at least five times the basal
      value. The reported results provide a coherent explanation of the critical role
      that hemodynamic factors may play in the early stages of atherogenic process.

PMID- 7738050
TI  - Tensile stress-strain characteristics of the human meniscal material.
AB  - The nonlinear stress-strain characteristics of the human menisci were determined
      by uniaxial elongation tests performed on circumferential and radial specimens
      prepared from different regions, layers, and locations. The properties of the
      collagen fibers and the matrix were calculated using the test results along with
      the values of the volume fractions of the meniscal components. Regression
      analysis showed that only three parameters, the elastic modulus, the maximum
      strain, and the strain intersect, are sufficient to define the nonlinear stress
      strain relation up to failure. For radial specimens, the layer had a significant
      effect (p < 0.01) on the elastic modulus and the maximum strain, but had no
      effect on the strain intersect and the maximum stress. For the same specimens,
      the region had a significant effect (p < 0.01) only on the strain intersect and
      the maximum stress. For circumferential specimens, analysis indicated no
      significant effect of either the region, the layer, or the location of the
      specimens on the material parameters defining the stress-strain relation.

PMID- 7738049
TI  - Muscle lines-of-action affect predicted forces in optimization-based spine muscle
      modeling.
AB  - This study describes the effects of varied torso muscle geometries commonly
      assumed in optimization-based muscle force prediction models. Specifically, the
      sensitivity of predicted muscle and spinal forces to assumed muscle lines-of
      action (LOA) is systematically examined. The practical significance of varied
      muscle LOAs is addressed by determining the relative precision needed for
      individual muscle LOAs and assessing which muscles are more critical to accurate
      prediction of spinal forces. To perform this analysis a nonlinear optimization
      model was used to generate muscle force predictions during combined frontal and
      sagittal plane moment loadings with an assumed erect posture. The LOAs of the
      erector spinae, rectus abdominus, internal and external oblique, and latissimus
      dorsi were systematically varied in the frontal and sagittal planes over an
      anatomically feasible range. The results indicated that moderate changes in the
      assumed LOA could substantially alter the magnitudes of predicted muscle and
      spinal forces. The estimated activity level of a muscle, as well as the predicted
      active/silent state could be affected by the LOA of that muscle and others. The
      patterns of predicted muscle activity, with respect to load orientation,
      underwent only minor alterations with changing LOA. The relative activation of
      several muscles, however, was dependent on LOA, and frequently led to variations
      in predicted spinal compression (> 100 N change) and shear forces (> 50 N
      change). This dependence of estimated spinal forces on assumed muscle geometry
      was most pronounced for the obliques and minimal for the more vertically oriented
      muscles and when loads were sagittally symmetric. This study suggests that muscle
      LOAs are critical inputs when interpreting absolute muscle and spinal force
      values predicted by models of physical exertions.

PMID- 7738051
TI  - Accuracy assessment of methods for determining hip movement in seated cycling.
AB  - The goal of this research was to examine the accuracy of three methods used to
      indicate the hip joint center (HJC) in seated steady-state cycling. Two of the
      methods have been used in previous studies of cycling biomechanics and included
      tracking a marker placed over the superior aspect of the greater trochanter, a
      location that estimates the center of rotation of the hip joint, and assuming
      that the hip is fixed. The third method was new and utilized an anthropometric
      relationship to determine the hip joint location from a marker placed over the
      anterior-superior iliac spine. To perform a comparative analysis of errors
      inherent in the three methods, a standard method which located the true hip joint
      center was developed. The standard method involved establishing a pelvis-fixed
      coordinate system using a triad of video markers attached to an intracortical
      pin. Three-dimensional motion analysis quantified the true hip joint center
      position coordinates. To provide data for the comparative analysis, the
      intracortical pin was anchored to a single subject who pedaled at nine cadence
      workrate combinations while data for all four methods were simultaneously
      recorded. At all cadence-workrate combinations the new method was more accurate
      than the trochanter method with movement errors lower by a factor of 2 in the
      vertical direction and a factor of 3 in the horizontal direction. Relative to the
      errors introduced by the fixed hip assumption, the new method was also generally
      more accurate by at least a factor of 2 in the horizontal direction and had
      comparable accuracy in the vertical direction. For computed kinetic quantities,
      the new method most accurately indicated hip joint force power but the fixed hip
      method most accurately indicated the work produced by the hip joint force over
      the crank cycle.

PMID- 7738052
TI  - An elastic compound tube model for a single osteon.
AB  - A model is developed whereby the secondary osteon--the dominant microstructural
      component of the cortical bone tissue--is considered as an n-layered cylinder
      with internal stresses in linear isotropic elasticity. An exact solution is
      obtained for a loading condition represented by a tensile-compressive force. The
      lengthening, the side deformation, and the strain energy of the system are
      explicitly calculated. The behavior of the main elastic quantities is illustrated
      by graphs. In particular, the important role played by the parity of the number
      of lamellae is revealed.

PMID- 7738055
TI  - A technical problem in the calculation of laminar flow near irregular surfaces
      described by sampled geometric data.
AB  - The numerical simulation of fluid flow and transport near biological surfaces
      must take into account the natural irregularity of these surfaces if the
      influence of the surface geometry on the near-wall flow field is to be modeled.
      If the geometric description of a biological surface has a limited resolution,
      what impact will this have on the accuracy of a computational simulation of the
      near-wall flow field? It is important to emphasize here that the problem arises
      from the limited number of data points describing the geometry and not from any
      limit on the number of mesh points in any subsequent calculation. In this note we
      show that if every point in a geometric data set describing an axisymmetric model
      of a diseased coronary artery is taken as a mesh point, then a well converged and
      otherwise accurately calculated wall shear stress distribution contains a degree
      of uncertainty which is attributable wholly to the limited resolution of the
      original geometric model. The approach taken is to repeat the numerical
      calculation on a reduced resolution version of the original geometric data set,
      comparing the wall shear stress distribution with that obtained originally. We
      conclude that accurate computational modeling and simulation of transport
      processes near irregular biological surfaces will be highly dependent on the
      availability of well-resolved geometric data describing the surface under study.

PMID- 7738053
TI  - On the minimization and maximization of the strain energy density in cortical
      bone tissue.
AB  - Universal minimization and maximization of the strain energy density, while
      possible in materials with cubic symmetry, is not possible for cortical long bone
      with its orthotropic material symmetry. Illustrating this point, it is shown that
      the stress state obtained when an axial load is applied along the long axis of a
      long bone at the midshaft is a minimizer of the strain energy density, while the
      stress state obtained when a load is applied perpendicular to the long axis, and
      perpendicular to the surface, of the mid-diaphysis of a long bone is a maximizer
      of the strain energy density. Thus, the bone tissue at the midshaft of a long
      bone is designed by nature so that it has the greatest stiffness in the direction
      of its long axis and its greatest impact loading resistance in the transverse
      direction.

PMID- 7738054
TI  - Numerical instabilities in bone remodeling simulations: the advantages of a node
      based finite element approach.
AB  - Long bone structure occurs in two distinct forms. The bone mass near the joint is
      primarily found in a distributed, porous trabecular structure, while in the
      diaphyses a tubular cortical structure is formed. It seems likely that these two
      observed morphologies come about, at least in part, as a mechanical adaptation to
      the different mechanical demands in the two regions. Mathematical formulations of
      this dependency have been proposed, thus facilitating numerical simulations of
      bone adaptation. Recently two types of discontinuities have been observed in
      these simulations. The first type (near-field) appears in areas near distributed
      load application and is characterized by a 'checkerboard' pattern of density
      wherein adjacent remodeled elements alternate between low and high density. The
      second type of discontinuity (far-field) appears remote from the load application
      and is characterized by strut or column-like regions of elements which become
      fully compact bone while adjacent regions are fully resorbed. In fact, the far
      field discontinuity is an accurate representation of bone physiology and
      morphology since it is consistent with the appearance of cortical bone in the
      diaphysis. On the other hand, the near-field discontinuity, appears in a region
      where continuous distributions of intermediate apparent densities (trabecular
      bone) are expected. This finding may cause some to question whether a single
      continuum formulation of bone remodeling can predict both discontinuous far-field
      behavior and continuous near-field behavior. We describe a node-based
      implementation of current continuum bone remodeling theories which eliminates the
      spurious near-field discontinuities and preserves the anatomically correct far
      field discontinuities, thus indicating that a single biological process may be at
      work in forming and maintaining both far-field and near-field morphologies.

PMID- 7738056
TI  - Bone strain gage data and theoretical models of functional adaptation.
AB  - The in vivo implantation of strain gages on the surface of bones has proven to be
      a very useful technique for studying the relationship between in vivo loading and
      bone growth and adaptation. However, data from such experiments have yet to be
      well incorporated within the context of theoretical models of bone adaptation.
      Methods for analyzing bone rosette strain gage recordings within the framework of
      strain energy density-based computational modeling/remodeling theories are
      presented. A new strain energy density based parameter, energy equivalent strain,
      is proposed as a single scalar measure of cyclic strain magnitudes and the
      concept of a daily strain stimulus is also introduced. As an illustrative
      example, the approach is applied to analyze previously reported in vivo data from
      the anteromedial human tibia (Lanyon et al., 1975, Acta orthop. Scand. 46, 256
      268).

PMID- 7738057
TI  - Elastic wave propagation in bone in vivo: methodology.
AB  - The purpose of this study was to investigate the usefulness of elastic wave
      propagation (EWP) in estimating the mechanical properties (elasticity) of human
      tibia. The test group was composed of 78-yr-old women assigned to high (n = 19)
      and low (n = 17) bone mineral density (BMD) groups as measured at the calcaneus
      by the 125I-photon absorption method. The EWP apparatus consisted of an impact
      producing hammer with a force strain gauge and two accelerometers positioned on
      the bone. Results for nylon and acrylic were used to calibrate the apparatus.
      Polyvinyl chloride (PVC) solid rods and tubes of various diameters were used to
      evaluate the relationship between the elastic wave velocity and cross-sectional
      area. The density and the cross-sectional area of tibia were measured by the
      computerized tomographic (CT) method at the same intersection points as velocity
      recordings. The velocities in tibia of bending waves produced by the mechanical
      hammer were found to depend on the density, area moment of inertia, and density
      dependent elastic constants of bone. It is important to account for the changes
      of these quantities along the bone. It is suggested that the velocity of elastic
      waves and various indices derived there from provide inexpensive ways of
      evaluating the elastic properties of bone.

PMID- 7738059
TI  - Comments on 'A video-based system for the estimation of the inertial properties
      of body segments'.

PMID- 7738058
TI  - Comment on 'The biphasic poroviscoelastic behavior of articular cartilage: role
      of the surface zone in governing the compressive behavior'.

PMID- 7738060
TI  - Changes in the mechanical properties of dermal sheep collagen during in vitro
      degradation.
AB  - The changes in tensile strength, elongation at break, and high strain modulus of
      dermal sheep collagen (DSC) during in vitro degradation using bacterial
      collagenase were studied. The changes in mechanical properties were compared with
      the change in weight of the samples as a function of degradation time. DSC was
      crosslinked with either glutaraldehyde (GA) or hexamethylene diisocyanate
      (HMDIC). During degradation, the changes in mechanical properties of the N-DSC, H
      DSC or G-DSC samples were more pronounced than the changes in the weight of the
      samples. Of the mechanical properties studied, the tensile strength was most
      susceptible to degradation of the DSC samples. After 2.5 h, N-DSC samples had
      lost only 55% of their initial weight, but the samples had no tensile strength
      left. Similar results were obtained for H-DSC, which retained no tensile strength
      after 24 h degradation, whereas only 45% of the initial weight was lost. G-DSC
      lost 3.5% of its weight after 24 h degradation, but only 25% of the initial
      tensile strength remained.

PMID- 7738061
TI  - Influence of ethylene oxide gas treatment on the in vitro degradation behavior of
      dermal sheep collagen.
AB  - The influence of ethylene oxide gas treatment on the in vitro degradation
      behavior of noncrosslinked, glutaraldehyde crosslinked or hexamethylene
      diisocyanate crosslinked dermal sheep collagen (DSC) using bacterial collagenase
      is described. The results obtained were compared with the degradation behavior of
      either nonsterilized or gamma-sterilized DSC. Upon ethylene oxide sterilization,
      reaction of ethylene oxide with the free amine groups of DSC occurred, which
      resulted in a decreased helix stability, as indicated by a lowering of the
      shrinkage temperature of all three types of DSC. Except for the low strain
      modulus the mechanical properties of the ethylene oxide sterilized materials were
      not significantly altered. gamma-Sterilization induced chain scission in all
      three types of DSC, resulting in a decrease of both the tensile strength and the
      high strain modulus of noncrosslinked and crosslinked DSC. When exposed to a
      solution of bacterial collagenase, ethylene oxide sterilized materials had a
      lower rate of degradation compared with nonsterilized DSC. This has been
      explained by a reduced adsorption of the collagenase onto the collagen matrix as
      a result of the introduction of pendant N-2-hydroxy ethyl groups.

PMID- 7738062
TI  - Cellular response to well-characterized calcium phosphate coatings and titanium
      surfaces in vitro.
AB  - The cellular response to well-characterized Ca-P and Ti surfaces was analyzed.
      This study indicated that the ion-beam sputtering process could produce a
      hydroxyapatite-type coating. However, structural alterations such as the
      incorporation of CO3 and the loss of the OH groups were observed. The Ti surfaces
      were shown to be predominantly amorphous TiO2. The in vitro cell culture study
      showed no significant differences in cell number for the Ti and Ca-P surfaces
      throughout the 12-day study. Furthermore, the initial percentage of protein
      within the cell layers was significantly lower for cells on Ca-P surfaces
      compared with the cell layer on Ti surfaces. However, after 3 h incubation, no
      significant difference in the percentage of protein was observed for the Ti and
      Ca-P surfaces.

PMID- 7738063
TI  - Biocompatibility study of as-polymerized poly(L-lactide) in rats using a cage
      implant system.
AB  - To evaluate the biocompatibility of in vitro predegraded as polymerized poly(L
      lactide) (PLLA), a cage implant system was used to investigate white cell and
      enzyme concentrations with time. The use of a cage permits in a serial fashion a
      quantitative and qualitative measurement of exudate components formed around an
      implant. Subcutaneously in rats, caped cages manufactured from stainless-steel
      mesh were implanted with in vitro predegraded, as-polymerized PLLA, as
      polymerized PLLA cylinders, and empty cages serving as controls. In vitro
      predegradation was used to simulate the degradation products of long-term in
      vitro degradation. Predegraded PLLA particles were obtained by in vitro
      hydrolysis at elevated temperatures. The first 7 days of implantation were
      characterized by an acute inflammatory reaction; the exudate extracted from the
      cages showed predominantly neutrophils for all types of implants. After day 7,
      there was a more chronic inflammatory reaction with predominantly macrophages and
      lymphocytes. There were no significant differences in the total leukocyte
      concentration or macrophage concentration for any of the cages in the period from
      10-21 days. Extracellular enzyme activity also did not show any significant
      differences among the three types of cages. A possible explanation for the
      absence of any significant differences could be that the in vitro predegraded
      particles were sieved before implantation, thus eliminating all small particles
      (< 70 microns) that are probably mandatory to provoke an increased cellular
      reaction.

PMID- 7738065
TI  - Histopathologic study following administration of liposome-encapsulated
      hemoglobin in the normovolemic rat.
AB  - Liposome encapsulated hemoglobin is being developed as an artificial
      resuscitative fluid for in vivo oxygen delivery. In the present report, we
      examine the effect of accumulation of liposome encapsulated hemoglobin on the
      structure of reticuloendothelial organs following administration of liposome
      encapsulated bovine hemoglobin in the normovolemic rat. We have also examined the
      administration of the liposome vehicle, tetrameric bovine hemoglobin, and
      liposome encapsulated bovine hemoglobin that had been lyophilized with 300 mM
      trehalose and rehydrated just before injection. Following injection into the tail
      vein, rats were sacrificed and liver, spleen, kidney, and lung harvested at 2 h,
      24 h, 1 week, and 2 weeks for analysis. Gross pathologic findings of animals
      injected with liposome encapsulated hemoglobin showed statistically significant
      splenomegaly with a waxy parenchymal pallor at early time points. Microscopic
      findings indicate that the liver and spleen are principally involved with
      liposome encapsulated hemoglobin removal over the course of 24 h with transient
      cytoplasmic vacuolization in tissue resident phagocytes as evidenced by both
      light and electron microscopic examination. Presence of liposome encapsulated
      hemoglobin in these vacuoles was confirmed by oil red O and prussian blue stains.
      Splenic weight was observed to decline after 24 h but still remained significant
      above sham-treated controls at 2 weeks and could be correlated with increased
      hematopoietic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738064
TI  - Improvement of blood compatibility on cellulose dialysis membrane. III. Synthesis
      and performance of water-soluble cellulose grafted with phospholipid polymer as
      coating material on cellulose dialysis membrane.
AB  - To improve the surface blood compatibility on a cellulose hemodialysis membrane,
      a blood compatible polymer with a phospholipid polar group, poly[2
      methacryloyloxyethyl phosphorylcholine(MPC)], was immobilized on the surface
      through the coating of a water-soluble cellulose grafted with poly(MPC) (MPC
      grafted cellulose, MGC). The MGC was synthesized by graft copolymerization of MPC
      on a water-soluble cellulose using cerium ion as an initiator. The coating
      process on the cellulose membrane with an aqueous solution of the MGC was
      convenient, and the MGC on the surface was not significantly detached even after
      immersion in water. The permeability and mechanical strength of the membrane
      coated with the MGC did not decrease compared with the original membranes. The
      MGC-coated cellulose membrane was blood compatible, as determined by the
      prevention of platelet adhesion and aggregation after contact with platelet-rich
      plasma. From these results, it is concluded that the MGC may be a useful material
      for improving the blood compatibility of the cellulose hemodialysis membrane.

PMID- 7738066
TI  - Silicone breast implants: the role of immune system on capsular contracture
      formation.
AB  - We evaluated the role of the immune system in the pathogenesis of the
      periprosthetic capsular contracture, the most frequently occurring complication
      following the implant of silicone prostheses. Peripheral blood samples from 22
      patients with silicone-gel-filled implants were examined. In all cases a capsule
      was felt by palpation, and it was classified according to the Baker scale. Ten
      patients (group 1) had a Baker 2 contracture, and 12 (group 2) had severe
      contracture rated 3 and 4. The cells positive to antigens CD3, CD4, CD8, HLA-DR,
      CD19, CD25, CD57, CD16, and CD14, and the cytotoxic activity of the lymphocytes
      on target cells K562 were assessed by cytofluorimetric analysis. At time 0 there
      were no statistically significant differences between patients and normal
      subjects, nor between the two groups. At 48 h, the group 2 patients had a
      number/mm3 of cells CD57 + significantly higher than both group 1 and control
      group (P < .05). In group 1 patients, the cytotoxic activity was similar to that
      of normal subjects, whereas in group 2 it was significantly increased, in respect
      to both the controls (P < .05) and group 1 (P < .001). In all groups, the contact
      of the lymphocytes with the silicone extract did not modify either the antigen
      expression or the lymphocyte functional activity. On the basis of these results
      we hypothesize the involvement of the immune system in the formation of the
      capsular contracture around the prosthesis.

PMID- 7738067
TI  - Sustained release of basic fibroblast growth factor from the synthetic vascular
      prosthesis using hydroxypropylchitosan acetate.
AB  - We designed a model vascular prosthesis consisting of expanded
      polytetrafluoroethylene (Gore Tex) loaded with basic fibroblast growth factor
      (bFGF), and studied its in vivo bFGF release behavior. To control the release
      rate of bFGF, biodegradable hydroxypropylchitosan acetate (HPCHA) was also
      incorporated into the Gore Tex disks with bFGF. HPCHA was dissolved in bFGF
      solution (180 micrograms/ml) at a concentration of 4% (wt/vol). A Gore Tex tube
      was cut into a length of about 5 cm and one end was sealed with a vascular clamp.
      The tube was then filled with resulting solution under appropriate pressure until
      the solvents seeped through the pores. The tube loaded with bFGF solution was
      freeze-dried and was cut into disks (0.75 cm in diameter). bFGF content in a
      HPCHA-free Gore disk was 2.05 +/- 0.32 micrograms (SE, n = 5). bFGF content in a
      HPCHA Gore disk was 2.71 +/- 0.41 micrograms (SE, n = 5). In an in vivo study in
      which the bFGF loaded Gore Tex disk was implanted in rabbit skin pockets, almost
      100% of bFGF from HPCHA-free disks was released within 24 h, whereas some 60%
      remained after 24 h in the HPCHA-loaded disks. HPCHA is a useful biodegradable
      carrier for controlling the release rate of the drug from the synthetic vascular
      prosthesis.

PMID- 7738068
TI  - Densely crosslinked polymer networks of poly(ethylene glycol) in
      trimethylolpropane triacrylate for cell-adhesion-resistant surfaces.
AB  - Densely crosslinked semi-interpenetrating polymer networks (semi-IPNs) of
      poly(ethylene glycol) (PEG) were synthesized by photopolymerizing a melt of PEG
      of various molecular weights and end-group functionalities in neat
      trimethylolpropane triacrylate (TMPTA). Increasing the molecular weight of PEG in
      the matrix from 1000 to 100,000 g/mol reduced the advancing and receding contact
      angles, contact angle hysteresis, and adsorption of human fibrinogen and bovine
      serum albumin. Crosslinked TMPTA homonetworks supported human fibroblast adhesion
      in vitro, whereas the resistance to cell adhesion of the semi-IPNs depended upon
      PEG molecular weight: Lower molecular weight PEG reduced the number of adherent
      cells; higher molecular weight PEG further reduced and eliminated cell adhesion,
      as did networks containing acrylate-functionalized PEG. A polymer system
      incorporated with PEG throughout a hydrophobic, densely crosslinked matrix,
      rather than as a blend or surface treatment, may be particularly useful for
      limiting biologic interactions when bulk material properties must be independent
      of the solvent environment and where surface abrasion may occur.

PMID- 7738069
TI  - Calcification of valved aortic allografts in rats: effects of age, crosslinking,
      and inhibitors.
AB  - Experiments were carried out to investigate rat aortic allograft calcification
      using valved abdominal aortic allografts. Results indicated that this was a
      potentially useful model for investigating fresh allograft calcification, as well
      as mineralization of glutaraldehyde-crosslinked valved allografts. Valve cusp
      results, however, were not comparable to those noted in large animal or human
      studies, while aortic wall calcification was more comparable. Calcification
      inhibitor investigations demonstrated that nearly complete inhibition of the
      calcification of the aortic wall of glutaraldehyde-crosslinked allografts was
      achieved using a number of individual inhibitors, including controlled release
      diphosphonates, and pretreatment with either ferric chloride or aluminum
      chloride. However, aminopropanehydroxydiphosphonate pretreatment was not
      efficacious, and sodium dodecyl sulfate pretreatment was only partially effective
      for inhibiting the aortic wall calcification in the glutaraldehyde-crosslinked
      allografts. It is concluded that valved aortic allografts in rats provide a
      useful model for investigating aortic wall (but not valve cusp) calcification and
      its inhibition.

PMID- 7738070
TI  - Cementum-impregnated gelatine membrane: its effect on periodontal tissue
      regeneration.
AB  - This study was designed to evaluate the ability of cementum-impregnated gelatine
      membranes (CGM) to stimulate regeneration of periodontal ligament following
      surgery. Three monkeys with no periodontal disease were used. Following flap
      elevation, recession type defects were created on the buccal side of maxillary
      lateral incisors and second premolars, and roots were subsequently planed.
      Experimental sites received CGM at approximately 2-3 mm below the cementoenamel
      junction while control sites received gelatine membrane (GM) free of cementum.
      Wounds were allowed to heal for 3 weeks, during which time daily plaque control
      measures were maintained. Tissues prepared from sacrificed animals revealed that
      experimental specimens exhibited formation of new cementum, new bone, and
      periodontal ligament. Control specimens exhibited connective tissue adhesion
      without either new cementum or significant new bone formation. Histometric
      analysis showed that the average vertical growth of cementum (NC) and bone (NB)
      at experimental sites were 3.48 +/- 0.29 and 0.64 +/- 0.43 mm, respectively. At
      the control sites the corresponding results were NC = 0.09 +/- 0.03 and NB = 0.06
      +/- 0.28. It was concluded that placement of CGM resulted in significantly
      greater postsurgical cementum and bone formation than that of GM alone.

PMID- 7738071
TI  - Micromechanisms of fatigue crack initiation and propagation in bone cements.
AB  - The micromechanisms of fatigue fracture in bone cements were explored and
      characterized in this investigation. Fatigue crack initiation sites were
      identified and the microscopic features responsible for crack initiation are
      illustrated. Differences in the fracture morphology of PMMA beads, in early crack
      growth and rapid crack growth stages, are brought out. Based on the fractographic
      features, a micromechanism of PMMA bead fracture is proposed.

PMID- 7738072
TI  - In vivo mechanical and histological characteristics of HA-coated implants vary
      with coating vendor.
AB  - The purpose of this study was to evaluate the interface attachment strength and
      histology of hydroxylapatite (HA) coated and uncoated titanium and cobalt
      chromium alloy implants. The canine transcortical plug model was utilized. Four
      different hydroxylapatite coatings were evaluated. In vitro analysis confirmed
      that all coatings met FDA guidelines for HA coatings. An unspecified FDA
      parameter, porosity was found to range from 5-15%. Mechanical testing of the bone
      implant interface demonstrated large variation in the performance of the
      coatings. However, further evaluation of two of the coatings did not demonstrate
      variations in mechanical characteristics. The histologic findings confirmed the
      mechanical testing results. The coatings which demonstrated the best mechanical
      characteristics had excellent bone apposition and uniformity and maintenance of
      the HA coating at all time periods upon histologic evaluation. Conversely, the
      coatings which demonstrated inferior mechanical characteristics demonstrated
      variable amounts of bone apposition and moderate to severe coating degradation
      and breakup. Cell-mediated osteolysis was observed in regions of severe coating
      degradation, and particle migration was noted in regions far from the interface.
      It was hoped that the four coatings would behave similarly as they all met
      current FDA guidelines. The only parameter which differed significantly among the
      coatings was coating porosity. Our results indicate that coatings with large
      porosities were associated with increased coating degradation and poor mechanical
      performance and osteolysis at the bone-coating interface.

PMID- 7738074
TI  - Human monocyte/macrophage adhesion and cytokine production on surface-modified
      poly(tetrafluoroethylene/hexafluoropropylene) polymers with and without protein
      preadsorption.
AB  - To study surface property-dependent human monocyte adhesion and cytokine (IL-1
      beta, IL-6, TNF-alpha) production, poly(tetrafluoroethylene/hexafluoropropylene)
      (FEP) polymer was modified to exhibit neutral, anionic, or cationic properties by
      incorporating amide (CONH2) and/or carboxyl (COOH) or aminoethyl amide
      [CONH(CH2CH2NH)nCH2CH2NH2] groups on the surface. Monocyte adhesion on surface
      modified FEP polymers and cytokines released by monocytes/macrophages (MC/MO)
      into the culture medium were compared to control tissue culture polystyrene
      (TCPS) at days 1 and 8. On day 1, the neutral surface FEP polymer with
      incorporated amide (NH2) groups showed the greatest inhibition of adhesion, 89%
      (P < .01), and cytokine production (IL-1 beta with 58%, IL-6 with 70%, and TNF
      alpha with 39%) compared to control TCPS. In contrast, the highly cationic
      [CONH(CH2CH2NH)nCH2CH2NH2] surface did not show significant (P > .01) inhibition
      of monocyte adhesion and cytokine production. When fibrinogen or IgG was
      preadsorbed to the surface, the inhibitory effects of the neutral surface FEP
      polymer on monocyte adhesion and cytokine production were not altered. In
      addition, other surface-modified FEP polymers showed similar inhibition of
      monocyte adhesion and cytokine production compared to TCPS. Specifically, as the
      incorporation of carboxyl (COOH) group content increased on FEP polymer surfaces,
      monocyte adhesion and cytokine production were also increased on day 1 with IgG
      preadsorption. On day 8, all surface-modified FEP polymers showed significant (P
      < .01) inhibition of monocyte adhesion when fibrinogen or IgG was preadsorbed.
      However, without protein (fibrinogen or IgG) preadsorption, monocyte adhesion was
      not significantly inhibited compared to control TCPS. In addition, cytokine
      production detected by ELISAs on day 8 showed no detectable levels of IL-1 beta
      and significantly decreased levels of IL-6 compared to day 1 for all tested
      polymers, with or without protein preadsorption. Interestingly, the level of TNF
      alpha production on day 8 remained high although not as high as on day 1. Based
      on these results, we suggest that FEP polymers with neutral hydrophilic surface
      properties may adhere and activate the least number of monocytes, which are
      important mediators of biocompatibility.

PMID- 7738075
TI  - Influence of discharge power level on the properties of hydroxyapatite films
      deposited on Ti6A14V with RF magnetron sputtering.
AB  - The effects of discharge radiofrequency (RF) power and film thickness were
      studied on the characteristics of Ca5(PO4)3OH (hydroxyapatite) thin films
      fabricated by RF magnetron sputtering. The structure and chemical composition
      were investigated with alpha-step (thickness), scanning electron microscopy
      (SEM), X-ray diffraction (XRD), Rutherford backscattering spectrometry (RBS), and
      infrared absorption spectrometry (FTIR). The films were analyzed as-sputtered and
      after annealing at 550 degrees C under argon flow. SEM showed that the film
      surfaces had no cracks or other defects. X-ray diffraction showed that the
      deposited films were amorphous with low-discharge RF power, and crystalline with
      high-discharge RF power. After annealing, all the films had the same crystalline
      structure as apatite. However, the RBS measurements revealed that all films had a
      higher calcium-phosphate ratio than standard synthetic hydroxyapatite.
      Furthermore, statistical testing of the RBS data revealed the existence of only a
      weak correlation between the Ca/P ratio and the discharge power level. Although
      all sputtered films showed phosphate bonds in the infrared spectrum, only after
      annealing did the OH bonds of hydroxyapatite become visible.

PMID- 7738073
TI  - Blood-biomaterial interactions in a flow system in the presence of bacteria:
      effect of protein adsorption.
AB  - An in vitro continuous flow system with whole human blood was used to study blood
      biomaterial interactions on a base polyurethane and three modified surfaces in
      the presence and absence of circulating Staphylococcus epidermidis. We
      hypothesized that the composition of the protein layer adsorbed on the surface of
      the biomaterial would influence the response of blood components and bacteria. We
      examined the test surfaces for adsorption of nine plasma proteins and adsorption
      profiles differed on the four surfaces. The positively charged surface, UC,
      adsorbed significantly higher amounts of fibronectin (P < .01), von Willebrand
      factor (P < .01), and fibrinogen (P < .05) than the other materials. As a
      consequence of increased adsorption of these adhesive proteins, the adhesion of
      platelets and bacteria was greater on UC than on any other surface. On the base
      polyurethane, BC, and the negatively charged surface, UA, protein adsorption was
      low, and these materials were largely free of adherent blood cells and bacteria.
      The heparinized surface, UH, adsorbed higher quantities (P < .01) of Hageman
      factor and high molecular weight kininogen relative to the other surfaces.
      Platelet adhesion, and surface coagulation were prominent on UC, and may have
      contributed to increased bacterial adhesion on this surface. In the presence of
      circulating bacteria, adsorption was generally lower than in the absence of
      bacteria. The pattern of protein adsorption was largely unaffected by the strain
      of circulating bacteria, but platelet responses (adhesion and activation) were
      greater in the presence of slime-producing S. epidermidis as compared to the non
      slime-producing strain, suggesting that slime may have a direct activating effect
      on platelets.

PMID- 7738076
TI  - Stress and age at menarche of mothers and daughters.
AB  - The hypothesis that psychological stress during early childhood leads to advanced
      reproductive maturation was assessed using data from the California Childhood
      Health and Development Study. Regression analyses failed to indicate that bed
      wetting, nightmares or thumb-sucking at age 5 predict age at menarche, regardless
      of controls for mother's age at menarche. Among socioeconomic variables suggested
      as contextual stressors measured at age 9-11 only mother's education was a
      significant predictor of daughter's age at menarche, though its effect is trivial
      compared to mother's age at menarche. Path analysis on a subsample of the
      subjects failed to demonstrate the hypothesised indirect effect of mother's age
      at menarche on daughter's age at menarche acting through early marriage and
      marital dissolution. These results cast doubt on the theory that early childhood
      stress is the key to divergent reproductive strategies among females based on the
      timing of reproductive maturation.

PMID- 7738078
TI  - Ethnicity and obstetric performance in Singapore.
AB  - The influence of ethnicity on obstetric performance in Singapore was assessed by
      retrospective analysis of all deliveries in the National University Hospital over
      a 7-year period. Malay mothers were younger, shorter, less educated, of higher
      parity, were more likely to have had no antenatal care, and had the highest
      incidence of premature labour. However, mothers of Indian origin had the smallest
      babies, the highest incidence of low birth weight and significantly higher
      perinatal mortality rates. Chinese mothers fared better than their Malay and
      Indian counterparts in all parameters assessed. The ethnic origin of the mother
      has an important bearing on perinatal performance. This emphasises the importance
      of designing appropriate strategies to improve perinatal health in the different
      ethnic groups.

PMID- 7738077
TI  - Coital frequency among married and cohabiting couples in the United States.
AB  - Coital frequency is studied among couples as a function of marital or cohabiting
      status, relationship duration, number of children, religious affiliation, income,
      education, fertility intentions, age, race, self-assessed health, time spent in
      work, and perceived relationship quality. Data are from the 1987-88 National
      Survey of Families and Households. Predictors of coital frequency that were
      stable across several analyses were male's and female's ages, the duration of the
      relationship, and the male partner's self-assessed health. When the discrepancy
      in partners' reports was adjusted, cohabitation status, number of children,
      future fertility intentions, religious affiliation, and relationship quality as
      assessed by the female partner were significant. The results suggest a
      substantial idiosyncratic component to the determination of coital frequency in
      relationships.

PMID- 7738079
TI  - Demographic perspectives on China and India.
AB  - This paper compares levels and trends of population growth rates, age and sex
      composition, mortality, and fertility including family planning practices in the
      world's two most populous countries, China and India. Both countries are
      undergoing demographic transition but China is nearer than India to achieving a
      stationary population. Fertility in China has declined below replacement level
      while in India it is nearly one and a half children per woman above replacement
      level. Both countries have achieved large reductions in mortality but life
      expectancy at birth in China is currently about 10 years longer than in India.
      Both countries have young populations but China will precede India in the aging
      of population structure during the 21st century.

PMID- 7738080
TI  - Infant and child mortality levels and trends in Bangladesh.
AB  - Infant and child mortality levels and trends in Bangladesh are examined using
      data from the 1989 Bangladesh Fertility Survey. Both infant and child mortality
      declined from the mid 1970s but infant mortality declined more quickly. The level
      of infant mortality in 1989 was around 100 per 1000 live births while child
      mortality (5q0) was 200 per 1000 live births. Life table analysis confirms the
      change in infant and child mortality. The decline in infant mortality is
      attributed to the introduction of improved public health measures and access to
      maternal and child health services.

PMID- 7738082
TI  - Influence of industrialisation on marital behaviour in Beduido (Estarreja),
      Portugal.
AB  - From marriage records of a Northern Portuguese parish for 1900-80, endogamy and
      exogamy rates were calculated for birthplace and residence in order to analyse
      the effect of industrialisation on the population structure after 1940. Marriages
      that were endogamous relative to birthplace decreased between 1940-49 (58.9%) and
      1988 (20.5%), while exogamy increased. Exogamous marriages in which people came
      from outside the municipality (51.92%) were greater than those of the surrounding
      region (42.04%). After industrialisation, the pattern of marriages changed for
      residence, with an increase in the number of individuals who came from the
      district to work in the factories and married. Industrialisation advanced the
      start of exogamy which, for most Portuguese populations, began later, in the
      1960s.

PMID- 7738081
TI  - Dimensions of occupations: genetic and environmental influences.
AB  - This study investigates the dimensions of occupation, and distances between
      occupational categories, by using intra-pair differences in adult occupational
      position for identical twins reared apart. Status and farm dimensions of
      occupation were identified. The results validate the use of occupational status
      as a dimension of occupational position. The causes of individual differences for
      the derived status dimension were also evaluated, based on groups of identical
      and fraternal twins reared apart or together. Genetic effects accounted for a
      substantial amount of the variance in occupational status for men, while shared
      and non-shared environmental effects were of about equal importance. For women,
      genetic effects were less important, and shared and non-shared environmental
      effects accounted for more of the variation. The results confirm that genetic
      effects are important sources of the familial resemblance often found for
      occupational status for men.

PMID- 7738083
TI  - Inter-individual and seasonal weight variation in rural Nepali women.
AB  - Changes in body weight were examined for non-pregnant women in rural Nepal, using
      183 anthropometric measures between the early winter and monsoon seasons in 1982,
      1982-83, 1990-91 and 1993. The women gained weight when work loads decreased
      after the monsoon, but despite substantial changes in total energy expenditure,
      which were out of phase with changes in food intake, seasonal changes were small,
      averaging only up to 2.6% of initial body weight. There were notable differences
      between individual women, changes in body weight ranging from -5.6 kg to 4.8 kg.
      Weight change was examined with respect to lactation status, age, body mass
      index, mid upper arm circumference and skinfolds as well as total energy
      expenditure and intake. Nonlactating women, very thin women and women aged under
      25 years gained more weight than their counterparts, both before and after the
      monsoon. Data for a sub-sample in 1982-83 indicated that women who maintained
      high physical activity levels throughout the year were less prone to weight loss
      than women whose activity fluctuated between seasons. Initial energy reserves,
      age-related maturation factors, levels of physical activity and energy intake
      combine to produce the notable inter-individual variation in body weight changes
      observed in this population.

PMID- 7738084
TI  - Perceptions of symptoms of severe childhood malaria among Mijikenda and Luo
      residents of coastal Kenya.
AB  - Effective community based malaria control programmes require an understanding of
      current perceptions of malaria as a disease and its severe manifestations.
      Quantitative and qualitative surveys of mothers on the Kenyan Coast suggest that
      fever is conceptualised in biomedical terms whereas the aetiology of severe
      malaria is perceived to be of more complex cultural origin. This is reflected in
      the treatments sought for convulsions. The results are discussed in the context
      of ethnographic factors. To be effective, future health information programmes
      must take cultural beliefs into account.

PMID- 7738085
TI  - Orthopaedic proceedings, 1994. Abstracts.

PMID- 7738086
TI  - XXI. Meeting of the European Tumor Virus Group (ETVG). Innsbruck, Austria, 8-12
      March 1995. Abstracts.

PMID- 7738087
TI  - Telomere length and proliferation potential of hematopoietic stem cells.
AB  - Hematopoietic stem cells have typically been defined as pluripotent cells with
      self-renewal capacity. Recent studies have shown striking differences in the mean
      length of telomeric repeat sequences at the end of chromosomes from human
      hematopoietic cells at different stages of development. The most likely
      explanation for these observations is that hematopoietic stem cells, like all
      other somatic cells studied to date, lose telomeric DNA upon each cell division.
      In this review, limitations in the replicative potential of hematopoietic stem
      cells are discussed in the context of possible clinical use of such cells for
      transplantation and gene therapy.

PMID- 7738089
TI  - Three-dimensional co-location of RNA polymerase I and DNA during interphase and
      mitosis by confocal microscopy.
AB  - The relative three-dimensional co-location of RNA polymerase I (RPI) and DNA was
      studied using confocal laser scanning microscopy during interphase and all the
      steps of mitosis in human cancerous cells. For each step of the cell cycle,
      immunolabeled RPI molecules and DNA specifically stained with chromomycin A3 were
      simultaneously imaged at high resolution through numerous optical sections. Then,
      all the data obtained were used to generate transverse sections, anaglyphs and
      volumic representations, which are all prerequisite approaches to a
      representative study of the three-dimensional organization of the nucleolus and
      the mitotic chromosomes. Our results indicated that in the interphasic nuclei, in
      which DNA is organized as a regular 3-D network, RPI was present within numerous
      irregular spheres arranged as several twisted necklaces. During metaphase, RPI
      labeling was segregated into pairs of spheres and typical crescent-shaped
      structures; both were centrally located within the set of chromosomes. During
      anaphase and telophase, a typical central and symmetric arrangement of labeled
      structures was systematically seen among the decondensing chromosomes, arranged
      as a regular cylinder and as a hollow half-sphere, respectively. This typical 3-D
      organization of structures containing RPI relative to DNA is another strong
      example of the non-random organization of the genome during interphase and
      mitosis.

PMID- 7738088
TI  - Osteogenic protein-1 promotes growth and maturation of chick sternal chondrocytes
      in serum-free cultures.
AB  - We examined the effect of recombinant human osteogenic protein-1 (OP-1, or bone
      morphogenetic protein-7), a member of the bone morphogenetic protein family, on
      growth and maturation of day 11, 15 and 17 chick sternal chondrocytes in high
      density monolayers, suspension and agarose cultures for up to 5 weeks. OP-1 dose
      dependently (10-50 ng/ml) promoted chondrocyte maturation associated with
      enhanced alkaline phosphatase activity, and increased mRNA levels and protein
      synthesis of type X collagen in both the presence and absence of serum. In serum
      free conditions, OP-1 promoted cell proliferation and chondrocyte maturation,
      without requiring either thyroid hormone or insulin, agents known to support
      chick chondrocyte differentiation in vitro. When grown in agarose under the same
      conditions, TGF-beta 1 and retinoic acid neither initiated nor promoted
      chondrocyte differentiation. The results demonstrate that OP-1, as the sole
      medium supplement, supports the maturation of embryonic chick sternal
      chondrocytes in vitro.

PMID- 7738090
TI  - Cell-to-cell adherens junction formation and actin filament organization:
      similarities and differences between non-polarized fibroblasts and polarized
      epithelial cells.
AB  - Cadherin has an intimate spatial relationship with actin filaments (AF) in
      various types of cells, forming the cell-to-cell adherens junction (AJ). We
      compared the AJ/AF relationship between non-polarized fibroblasts (NRK cells) and
      polarized epithelial cells (MTD-1A cells). E/P-cadherin, alpha-catenin, ZO-1 and
      vinculin were localized with reference to AF in these cells using laser scan
      microscopy as well as conventional light and electron microscopy. NRK cells
      adhered to each other at the tips of thin cellular processes, where spot-like AJ
      were formed, where P-cadherin, alpha-catenin, ZO-1 and vinculin were
      concentrated. Some stress-fiber-like AF bundles ran axially in these processes
      and terminated at spot-like AJ on their tips. At the electron microscopic level
      these spot-like AJ were seen as aggregates of small 'units' of AJ, where AF were
      densely and perpendicularly associated with the plasma membrane. In MTD-1A cells,
      the AJ/AF relationship was investigated during the cell polarization process
      after replating or wounding. At the early stage, the AJ/AF relationship was quite
      similar to that in NRK cells. As polarization proceeded, the spot-like AJs were
      gradually fused side by side with the concomitant shortening of the associated
      stress-fiber-like AF bundles. Finally, the belt-like AJ was established, which
      was lined with circumferential AF bundles. The similarities and differences in
      the AJ/AF relationship between non-polarized fibroblasts and polarized epithelial
      cells are discussed.

PMID- 7738091
TI  - The exit of mouse oocytes from meiotic M-phase requires an intact spindle during
      intracellular calcium release.
AB  - To study the role of the metaphase spindle during the period of oocyte
      activation, mouse oocytes were fertilised or activated parthenogenetically in the
      presence or absence of the microtubule inhibitor nocodazole. In both cases,
      nocodazole caused the disappearance of the spindle and prevented the passage of
      the oocytes into interphase. However, the calcium spiking responses of the
      oocytes were not affected by nocodazole, being repetitive after fertilisation and
      a single spike after activation. If, after their activation or fertilisation in
      nocodazole, oocytes were later removed from the drug, only those that had been
      fertilised progressed into interphase. This progress was associated with
      continuing calcium spiking. Moreover, both the spiking and the progress to
      interphase could be blocked or reduced in incidence by removal of external
      calcium or addition of 5,5'-dimethyl BAPTA-AM. Oocytes that had been activated by
      ethanol in the presence of nocodazole and then removed from it, to allow re
      formation of the spindle, only progressed into interphase if given a second
      exposure to ethanol, thereby eliciting a second calcium transient. These results
      show that exit from meiotic M-phase requires the simultaneous presence of a fully
      intact spindle during the release of calcium and that those factors leading to
      the degradation of cyclin B are only activated transiently. Since cyclin is being
      degraded continuously in the metaphase-II-arrested mouse oocyte and since this
      degradation is microtubule-dependent, these data suggest that the superimposition
      of a high concentration of intracellular calcium is required to tilt the
      equilibrium further in favour of cyclin degradation if exit from M-phase is to
      occur.

PMID- 7738092
TI  - Direct involvement of a lamin-B-related (54 kDa) protein in the association of
      intermediate filaments with the postsynaptic membrane of the Torpedo marmorata
      electrocyte.
AB  - Mechanisms by which motor innervation induces postsynaptic membrane
      differentiation and functional compartmentalization of the subneural sarcoplasm
      in skeletal muscle fibres are still poorly understood. However, transmembrane
      control of cytoskeletal activities by the nerve terminal may be considered. Here,
      we examine several properties of a 54 kDa protein, previously identified in the
      postsynaptic membrane of the Torpedo marmorata electrocyte with anti-lamin B
      antibodies, in order to study its role in the assembly of the subneural
      intermediate filament meshwork. Using a ligand blot assay, we show that this
      protein binds desmin, a type III intermediate filaments protein, at micromolar
      concentrations. Moreover, purified acetylcholine receptor-rich membrane fragments
      are able to generate arrays of desmin filaments in vitro. Immunofluorescence
      experiments indicate that the 54 kDa protein becomes associated with the
      acetylcholine receptor-rich membrane at an early stage of development of the
      electrocyte, and that a polarized desmin network develops concomitantly from the
      postsynaptic membrane. Taken together, these data show that, like karyoskeletal
      lamin B, the 54 kDa protein is involved in the organization of the subneural
      intermediate filament meshwork. Control of the assembly of the subneural
      cytoskeleton by components of the postsynaptic membrane may thus be a
      prerequisite for the functional compartmentalization of the muscle fibre
      triggered by motor innervation.

PMID- 7738093
TI  - Characterization of moesin in the sea urchin Lytechinus variegatus:
      redistribution to the plasma membrane following fertilization is inhibited by
      cytochalasin B.
AB  - We have investigated the distribution and function of an ezrin-radixin-moesin
      like (ERM) molecule in the sea urchin. A sea urchin homologue of moesin was
      cloned that shares 75% amino acid similarity in the conserved N-terminal region
      to other moesin molecules. A 6.3 kb message is transcribed late in embryogenesis
      and is present in adult tissues. Polyclonal antibodies were generated to proteins
      expressed by a bacterial expression vector, and affinity purified. These
      antibodies recognize a single 75 kDa protein that is present throughout
      development in approximately equal abundance, and specifically they immuno
      precipitate a single protein. We show by immunolocalization that SUmoesin has two
      predominant patterns during development. First, SUmoesin is rapidly redistributed
      after fertilization from a location throughout the egg cytoplasm to a location in
      the egg cortex. Later in embryogenesis, SUmoesin is localized to the apical ends
      of cells in the regions of cell-cell junctions. We show that SUmoesin is present
      in actin-rich regions of the embryo. Finally, we show that the location of
      SUmoesin requires an intact actin-based cytoskeleton. SUmoesin fails to localize
      to the plasma membrane after fertilization in the presence of cytochalasin B.
      Furthermore, SUmoesin loses its apical position in the region of cell-cell
      junctions in the presence of cytochalasin B in later stages of embryogenesis.
      This effect is reversible, and the microtubule inhibitor colchicine has no
      effect. These results show that SUmoesin becomes associated with apical plasma
      membrane structures early in development, and that SUmoesin is both coincident
      with actin and requires the assembly of actin filaments to maintain its
      localization.

PMID- 7738094
TI  - Molecular analysis of a cytoplasmic dynein light intermediate chain reveals
      homology to a family of ATPases.
AB  - Cytoplasmic dynein is a multi-subunit complex involved in retrograde organelle
      transport and some aspects of mitosis. In previous work we have cloned and
      sequenced cDNAs encoding the rat cytoplasmic dynein heavy and intermediate
      chains. Here we report the cloning of the remaining class of cytoplasmic dynein
      subunits, which we refer to as the light intermediate chains (LICs: 53-59 kDa).
      Four LIC electrophoretic bands were resolved in purified bovine cytoplasmic
      dynein preparations by one-dimensional gel electrophoresis. These four bands were
      simplified to two bands (LIC53/55 and LIC57/59) by alkaline phosphatase
      treatment. N-terminal amino acid sequence was obtained from a total of 11
      proteolytic peptides generated from both LIC53/55 and LIC57/59. Overlapping cDNA
      clones encoding LIC53/55 were isolated by oligonucleotide screening using probes
      based on the LIC53/55 peptide sequence. The cDNA sequence contained a 497 codon
      open reading frame encoding a polypeptide with a molecular mass of approximately
      55 kDa. Each of the LIC53/55 peptides was found within the deduced amino acid
      sequence, as well as four of the LIC57/59 peptides. Analysis of the LIC53/55
      primary sequence revealed homology with the ABC transporter family of ATPases in
      the region surrounding the P-loop sequence element. Together these data identify
      the LICs as a novel family of dynein subunits with potential ATPase activity.
      They also reveal that the complexity of the LICs is due to both post
      translational modification and the existence of at least two LIC polypeptides for
      which we propose the names LIC-1a and LIC-2.

PMID- 7738095
TI  - Interaction of chromosome-6-encoded dystrophin related protein with the
      extracellular matrix.
AB  - Dystrophin-related protein/utrophin is a large, cytoskeletal protein that shares
      significant sequence similarity with dystrophin. Dystrophin-related protein is
      known to be enriched where cell-extracellular matrix contacts are well defined;
      however, the mechanism of dystrophin-related protein enrichment and its
      functional role(s) at these sites are yet to be defined. Here, we demonstrate
      that dystrophin-related protein is concentrated in patches of astrocyte membrane
      in apposition with the extracellular matrix and that the distribution of
      dystrophin-related protein is temporally modulated by the extracellular matrix
      constituent laminin. Furthermore, we demonstrate the existence of a specific
      biochemical association between dystrophin-related protein and laminin in
      astrocytes. In these astrocytes, the depletion of dystrophin-related protein by
      the use of antisense dystrophin-related protein oligonucleotides causes marked
      reduction in the formation of functional substratum-membrane attachments. Taken
      together, these data suggest that dystrophin-related protein may function in the
      generation and maintenance of regional substratum-associated membrane
      specializations, such as those found at the blood-brain barrier.

PMID- 7738096
TI  - Nucleolar localisation of three Hox homeoproteins.
AB  - Homeoproteins encoded by genes of the Hox family are nuclear proteins believed to
      act as transcription factors and to participate in the determination of the body
      plan. Here we show that in several vertebrate cells, they exhibit a subnuclear
      localisation associated with the nucleolus. We used monoclonal antibodies to
      study the distribution of three homeoproteins, namely HOXB7, HOXC6 and HOXD4. The
      immunoreactivity to antibodies against HOXC6 protein in Xenopus laevis embryonic
      tissues is restricted to one or two spots within the nucleus; this distribution
      partially overlaps that of fibrillarin, a protein of the fibrillar zone of the
      nucleoli. Indirect immunofluorescence analysis of the distribution of HOXB7
      protein in 3T3 cells, and of HOXD4 protein in human neuroblastoma and Raji
      lymphoma cell lines and activated lymphocytes, results invariably in a nucleolar
      localisation. Purified nucleoli from stimulated T lymphocytes, and Raji cells
      contain an activity capable of binding, in a gel retardation assay, to an
      oligonucleotide specifically recognised by the HOXD4 homeoprotein. This activity
      is specifically removed by anti-HOXD4 antibodies and is found associated in
      southwestern blots with a single band with an apparent M(r) of 30,000,
      corresponding to that of recombinant HOXD4. The functional significance of the
      nucleolar localisation of Hox proteins remains to be determined.

PMID- 7738097
TI  - Dermal fibroblasts convert to a myogenic lineage in mdx mouse muscle.
AB  - Duchenne muscular dystrophy is a primary muscle disease that manifests itself in
      young boys as a result of a defect in a gene located on the X-chromosome. This
      gene codes for dystrophin, a normal muscle protein that is located beneath the
      sarcolemma of muscle fibres. Therapies to alleviate this disease have centred on
      implanting normal muscle precursor cells into dystrophic fibres to compensate for
      the lack of this gene and its product. To date, donor cells for implantation in
      such therapy have been of myogenic origin, derived from paternal biopsies.
      Success in human muscle, however, has been limited and may reflect immune
      rejection problems. To overcome this problem the patient's own myogenic cells,
      with the dystrophin gene inserted, could be used, but this could lead to other
      problems, since these cells are those that are functionally compromised by the
      disease. Here, we report the presence of high numbers of dystrophin-positive
      fibres after implanting dermal fibroblasts from normal mice into the muscle of
      the mdx mouse-the genetic homologue of Duchenne muscular dystrophy. Dystrophin
      positive fibres were also abundant in mdx muscle following the implantation of
      cloned dermal fibroblasts from the normal mouse. Our results suggest the in vivo
      conversion of these non-myogenic cells to the myogenic pathway resulting in the
      formation of dystrophin-positive muscle fibres in the deficient host. The use of
      dermal fibroblasts may provide an alternative approach to the previously
      attempted myoblast transfer therapy, which in human trials has yielded
      disappointing results.

PMID- 7738098
TI  - rab8 in retinal photoreceptors may participate in rhodopsin transport and in rod
      outer segment disk morphogenesis.
AB  - Small GTP-binding protein rab8 regulates transport from the TGN to the
      basolateral plasma membrane in epithelial cells and to the dendritic plasma
      membrane in cultured hippocampal neurons. In our approach to identify proteins
      involved in rhodopsin transport and sorting in retinal photoreceptors, we have
      found, using [32P]GTP overlays of 2D gel blots, that six small GTP-binding
      proteins are tightly bound to the post-Golgi membranes immunoisolated with a mAb
      to the cytoplasmic domain of frog rhodopsin. We report here that one of these
      proteins is rab8. About 50% of photoreceptor rab8 is membrane associated and
      approximately 13% is tightly bound to the post-Golgi vesicles. By confocal
      microscopy, antibody to rab8 specifically labels calycal processes and the actin
      bundles of the photoreceptor inner segment that extend inward to the junctional
      complexes that comprise the outer limiting membrane. Anti-rab8 shows a striking
      periodicity of high density labeling at 1 +/- 0.12 microns intervals along the
      actin bundles. Rhodopsin-bearing post-Golgi membranes cluster around the base of
      the cilium where rab8 and actin are also co-localized, as revealed by confocal
      microscopy of retinal sections double labeled with anti-rab8 and phalloidin.
      Microfilaments have been implicated in rod outer segment (ROS) disk
      morphogenesis. Our data suggest that rab6, which we have previously localized to
      the post-Golgi compartment, and rab8 associate with the post-Golgi membranes
      sequentially at different stages of transport. rab8 may mediate later steps that
      involve interaction of transport membranes with actin filaments and may
      participate in microfilament-dependent ROS disk morphogenesis.

PMID- 7738099
TI  - Activation of the small GTP-binding proteins rho and rac by growth factor
      receptors.
AB  - The small GTP-binding proteins, rho and rac, control signal transduction pathways
      that link growth factor receptors to the activation of actin polymerization. In
      Swiss 3T3 cells, rho proteins mediate the lysophosphatidic acid and bombesin
      induced formation of focal adhesions and actin stress fibres, whilst rac proteins
      are required for the platelet-derived growth factor-, insulin-, bombesin- and
      phorbol ester (phorbol 12-myristate 13-acetate)-stimulated actin polymerization
      at the plasma membrane that results in membrane ruffling. To investigate the role
      of p85/p110 phosphatidylinositol 3-kinase in the rho and rac signalling pathways,
      we have used a potent inhibitor of this activity, wortmannin. Wortmannin has no
      effect on focal adhesion or actin stress fibre formation induced by
      lysophosphatidic acid, bombesin or microinjected recombinant rho protein. In
      contrast, it totally inhibits plasma membrane edge-ruffling induced by platelet
      derived growth factor and insulin though not by bombesin, phorbol ester or
      microinjected recombinant rac protein. We conclude that phosphatidylinositol
      3,4,5 trisphosphate mediates activation of rac by the platelet-derived growth
      factor and insulin receptors. The effects of lysophosphatidic acid on the Swiss
      3T3 actin cytoskeleton can be blocked by the tyrosine kinase inhibitor,
      tyrphostin. Since tyrphostin does not inhibit the effects of microinjected rho
      protein, we conclude that lysophosphatidic acid activation of rho is mediated by
      a tyrosine kinase.

PMID- 7738100
TI  - The role of protein phosphorylation in the assembly of a replication competent
      nucleus: investigations in Xenopus egg extracts using the cyanobacterial toxin
      microcystin-LR.
AB  - Cell-free extracts of Xenopus eggs support nuclear assembly and DNA replication
      in vitro. Extracts supplemented with the protein phosphatase inhibitor
      microcystin-LR displayed various inhibitory effects at different concentrations
      of the toxin. In the presence of cycloheximide, additions of microcystin did not
      induce histone H1-kinase activity. Nevertheless, increasing concentrations of
      microcystin did sequentially prevent DNA replication, nuclear lamina assembly and
      nuclear envelope assembly. DNA replication was prevented when microcystin was
      added at 250 nM. Furthermore, this effect could be reversed after the addition of
      the catalytic sub-unit of protein phosphatase 2A to inhibited extracts. At a
      concentration of 250 nM microcystin, nuclear membrane assembly, nuclear lamina
      assembly and nuclear transport all occurred in egg extracts. In addition single
      stranded M13 DNA replication was also permitted. However, it appeared that
      replicase assembly was not completed, since nuclei assembled in microcystin
      treated extracts displayed an unusual distribution of proliferating cell nuclear
      antigen (PCNA). Although PCNA was located at sites that resembled pre-replication
      foci, this nuclear protein was readily solubilised when nuclei were isolated and
      extracted sequentially with Triton, nucleases and salts. Despite this, nuclei
      containing pre-assembled replication forks could synthesise DNA when transferred
      into microcystin-treated extracts.

PMID- 7738101
TI  - A protein similar to the 67 kDa laminin binding protein and p40 is probably a
      component of the translational machinery in Urechis caupo oocytes and embryos.
AB  - Oocytes of the echiuroid, Urechis caupo, contain an abundant maternal mRNA that
      encodes a protein very similar to LBP/p40, originally identified as a non
      integrin 67 kDa laminin binding protein. We have sequenced the Urechis caupo mRNA
      for LBP/p40, and a similar mRNA from the Hawaiian sea urchin, Tripneustes
      gratilla. Both of the encoded proteins, as well as LBP/p40 proteins from other
      sources, share significant homology in the amino 2/3 of the proteins, but diverge
      extensively at the carboxyl ends. LBP/p40 protein is present in growing and in
      full-grown U. caupo oocytes. The protein concentration remains constant for the
      first 48 hours of embryogenesis and then begins to decline. In sucrose gradients
      run with homogenates from coelomocytes, oocytes, and early embryos, all of the
      LBP/p40 protein appears to be associated with either polysomes or free 40 S
      ribosomal subunits. In later embryos, an increasing proportion of the protein is
      found in the soluble fraction. Immunohistochemistry indicates that LBP/p40 is
      uniformly distributed in early U. caupo embryos, with no localization at the cell
      surface. In later embryos LBP/p40 is localized in specific parts of the embryo
      which may correspond to neural tissue.

PMID- 7738102
TI  - Divergent modes of autophagy in the methylotrophic yeast Pichia pastoris.
AB  - The budding yeast Pichia pastoris responds to methanolic media by synthesizing
      high levels of cytosolic enzymes (e.g. formate dehydrogenase) and peroxisomal
      enzymes (e.g. alcohol oxidase), which are necessary to assimilate this carbon
      source. Major alterations in cellular metabolism are initiated upon a shift in
      carbon source to ethanol or glucose. These alterations require the synthesis of
      new proteins and the rapid degradation of those enzymes no longer needed for
      methanol utilization. In this study, we have measured cytosolic and peroxisomal
      enzyme activities and examined the fate of morphologically distinct peroxisomes
      to assess the degradative response of this yeast during nutrient adaptation.
      Utilizing biochemical, morphological and genetic approaches, we have shown that
      there exist in P. pastoris at least two pathways for the sequestration of
      peroxisomes into the vacuole for degradation. The ethanol-induced pathway is
      independent of protein synthesis and includes an intermediate stage in which
      individual peroxisomes are sequestered into autophagosomes by wrapping membranes,
      which then fuse with the vacuole. This process is analogous to macroautophagy.
      The glucose-induced pathway invokes the engulfment of clusters of peroxisomes by
      finger-like protrusions of the vacuole by a process analogous to microautophagy.
      Unlike ethanol adaptation, glucose stimulated the degradation of formate
      dehydrogenase as well. Peroxisomes remained outside the vacuoles of glucose
      adapted cycloheximide-treated normal cells, suggesting that protein synthesis is
      required for peroxisome entry into the yeast vacuole. Two complementary mutants
      (gsa1 and gsa2) that are unable to degrade peroxisomes or formate dehydrogenase
      during glucose adaptation were isolated. The mutated gene products appear to
      function in one or more events upstream of degradation within the vacuole, since
      ethanol-induced peroxisome degradation proceeded normally in these mutants and
      peroxisomes were found outside the vacuoles of glucose-adapted gsa2 cells.
      Mutants lacking vacuolar proteinases A and B were unable to degrade alcohol
      oxidase or formate dehydrogenase during ethanol or glucose adaptation.
      Peroxisomes were found to accumulate within the vacuoles of these proteinase
      mutants during adaptation. Combined, the results suggest that there exist in
      Pichia pastoris two independent pathways for the sequestration of peroxisomes
      into the vacuole, the site of degradation.

PMID- 7738103
TI  - Direct interaction of nucleoporin p62 with mRNA during its export from the
      nucleus.
AB  - Primary transcripts in eukaryotic cells undergo several processing steps within
      the nucleus, and resulting mature RNA molecules are selectively exported to the
      cytoplasm. Nucleo-cytoplasmic mRNA transport is an active process that likely
      involves RNA-protein interactions. To identify specific RNA-binding proteins, we
      designed a novel approach, which allows the analysis of interactions between
      mRNAs and proteins along the transport pathway. The method consists of inducing
      in vivo a covalent binding between nuclear proteins and microinjected mRNAs.
      Using such a procedure, we were able to detect a direct interaction between
      nucleoporin p62 with mRNA during export. The formation of the mRNA-p62 complex
      was inhibited by wheat-germ agglutinin, an inhibitor of mRNA export. Antibodies
      directed against p62 caused a substantial reduction in the rate of mRNA export
      from the nucleus.

PMID- 7738105
TI  - Lamin A precursor is localized to intranuclear foci.
AB  - Lamin A is synthesized in the cytoplasm as a precursor bearing a carboxyl
      terminal CaaX box or isoprenylation signal. This precursor is post
      translationally processed through multiple steps: isoprenylation with a farnesyl
      residue on the cysteine of the CaaX box, proteolytic removal of the last three
      amino acids, carboxymethylation of the cysteine residue and, finally, proteolytic
      removal of 15 amino acids from the carboxyl terminus. This last step gives rise
      to mature lamin A from which the isoprenylated terminus has been removed.
      Isoprenylation is a prerequisite for all other steps of processing. The
      subcellular location of these processing steps for lamin A is still a matter of
      debate. We have produced an antibody specific to the 18 amino acid carboxyl
      terminus of the lamin A precursor that does not recognize mature lamin A. This
      antibody detects intranuclear foci by immunofluorescence. Larger amounts of lamin
      A precursor were accumulated by treating cells with mevinolin (MVN), an inhibitor
      of isoprenoid synthesis. In MVN-treated cells, the lamin A precursor accumulated
      most strikingly in the peripheral nuclear lamina where it was assembled, while
      intranuclear foci were maintained. The addition of an excess of mevalonate (MVA),
      which restores isoprenylation activity, to MVN-treated cells led to a progressive
      disappearance of the lamin A precursor from the peripheral lamina. This process
      was completed after 4 hours of MVA treatment, after which the lamin A precursor
      was restricted to intranuclear foci. We conclude from these results that the non
      isoprenylated lamin A precursor appears competent for assembly into the
      peripheral nuclear lamina, and that all the processing steps leading to mature
      lamin A can occur within the nuclear space.

PMID- 7738104
TI  - A yeast protein that bidirectionally affects nucleocytoplasmic transport.
AB  - We have identified a temperature-sensitive mutant of Saccharomyces cerevisiae
      (npl3) that accumulates polyadenylated RNA in the nucleus at 37 degrees C, as
      judged by in situ hybridization. The strong nuclear signal is not simply due to
      increased cytoplasmic turnover of mRNA, as reincubation at 37 degrees C with an
      RNA polymerase inhibitor shows no diminution in the in situ signal. Over several
      hours at 37 degrees C, the average poly(A) tail length increases and a
      characteristic ultrastructural alteration of the nucleoplasm occurs. Cloning and
      sequencing indicate that the corresponding gene is NPL3/NOP3, which codes for a
      nucleolar/nuclear protein implicated in protein import into the nucleus (Bossie
      et al. (1992). Mol. Biol. Cell 3, 875-893) and in rRNA maturation (Russell and
      Tollervey (1992). J. Cell Biol. 119, 737-747). NPL3 includes bipartite RNA
      recognition motifs (RRM) and a Gly-Arg repeat domain, as in several nucleolar
      proteins. A point mutation adjacent to one of the RRM has been identified in the
      ts copy of the gene. Although this protein is not concentrated in nuclear pores,
      NPL3 is implicated in both import and export from the nucleus. Judging from the
      site of the npl3 mutation and since the block in RNA export can be detected prior
      to an obvious nuclear import defect in npl3, the defect in RNA export may be
      primary. Since other mutants that interrupt RNA export do not block protein
      import, the NPL3 protein itself appears to be implicated in protein import.

PMID- 7738106
TI  - Identification of subcellular compartments containing peptidylglycine alpha
      amidating monooxygenase in rat anterior pituitary.
AB  - Both soluble and integral membrane forms of peptidylglycine alpha-amidating
      monooxygenase (PAM) are expressed in the rat anterior pituitary, making it an
      ideal model system for studying the routing of proteins into secretory granules.
      To identify the subcellular compartments involved in the routing of integral
      membrane PAM, we used subcellular fractionation, metabolic labeling and
      immunoblot analysis. Mature secretory granules were found to contain full-length
      integral membrane PAM along with a significant amount of soluble PAM generated by
      endoproteolytic cleavage. PAM proteins were not co-distributed with
      tyrosylprotein sulfotransferase activity during sucrose gradient centrifugation,
      indicating that the trans-Golgi/TGN is not a major PAM-containing compartment at
      steady state. Fractionation of the 4,000 g and 10,000 g pellets obtained by
      differential centrifugation identified a significant amount of integral membrane
      PAM in a light fraction lacking soluble secretory granule proteins. Metabolic
      labeling experiments with primary anterior pituitary cells demonstrated that
      integral membrane PAM enters a light compartment with similar properties only
      after exit from the trans-Golgi/TGN. Comparison of the metabolic labeling and
      immunoblot analyses suggests that PAM in this post-trans-Golgi/TGN compartment is
      in organelles involved in the intracellular recycling of integral membrane PAM.
      Small amounts of full-length integral membrane PAM were also recovered in
      fractions containing internalized transferrin and may be in an endosomal
      compartment following retrieval from the cell surface.

PMID- 7738107
TI  - Protein storage vacuoles form de novo during pea cotyledon development.
AB  - We have investigated the formation of protein storage vacuoles in peas (Pisum
      sativum L.) in order to determine whether this organelle arises de novo during
      cotyledon development. A comparison of different stages in cotyledon development
      indicates that soluble protease activities decline and the amounts of storage
      proteins and the integral membrane protein of the protein body, alpha-TIP,
      increase during seed maturation. On linear sucrose density gradients we have been
      able to distinguish between two separate vesicle populations: one enriched in
      alpha-TIP, and one in TIP-Ma 27, a membrane protein characteristic of vegetative
      vacuoles. Both vesicle populations possess, however, PPase and V-ATPase
      activities. Conventionally fixed cotyledonary tissue at an intermediate stage in
      cotyledon development reveals the presence of a complex tubular-cisternal
      membrane system that seems to surround the pre-existing vacuoles. The latter
      gradually become compressed as a result of dilation of the former membrane
      system. This was confirmed immunocytochemically with the TIP-Ma 27 antiserum.
      Deposits of the storage proteins vicilin and legumin in the lumen, and the
      presence of alpha-TIP in the membranes of the expanding membrane system provide
      evidence of its identity as a precursor to the protein storage vacuole.

PMID- 7738108
TI  - Interleukin-8 induces motile behavior and loss of focal adhesions in primary
      fibroblasts.
AB  - Interleukin-8 (IL-8) is a proinflammatory cytokine that promotes neutrophil
      migration. Although fibroblasts are known to secrete IL-8, the actions of this
      cytokine on fibroblasts have not been previously reported. We have found that in
      subconfluent populations of cultured primary fibroblasts, IL-8 causes an increase
      in the percentage of cells lacking focal adhesions. Most of the IL-8-stimulated
      cells not only exhibit a lack of focal adhesions but also have a migratory
      phenotype that includes a protrusive leading edge and trailing tail. In addition,
      IL-8 was found to promote primary fibroblast chemotaxis in modified Boyden
      chambers as well as chemokinesis on serum-coated coverslips. Human primary
      fibroblasts were also found to specifically bind to IL-8 with high affinity. We
      have previously shown that a lack of focal structures in primary fibroblasts can
      be used as an index of chemokinetic locomotion and have fully characterized this
      system using newborn rat heart conditioned medium. The main stimulus in heart
      conditioned medium that is responsible for the lack of focal adhesions in the
      majority of cells can be immunoprecipitated using a polyclonal antibody against
      recombinant human IL-8. Additionally, video microscopy assays using heart
      conditioned medium depleted with the IL-8 antibody show an increase in the
      percentage of stationary cells, a consequent decrease in the percentage of
      migrating cells, and a twofold increase in the mitotic rate. Interleukin-1 alpha
      and tumor necrosis factor-alpha, which are early inflammatory cytokines, have
      been previously shown to stimulate IL-8 production in macrophages, fibroblasts,
      endothelial and epithelial cells. Our findings indicate that these two cytokines
      also cause an increase in the percentage of fibroblasts without focal adhesions.
      Additionally, this increase in cells lacking focal structures can be largely
      attributed to the production and subsequent autocrine action of a factor
      immunoprecipitated with an IL-8 antibody. Conversely, GRO-alpha, which has a high
      homology with IL-8, does not cause a similar increase in the percentage of cells
      lacking focal adhesions, but was not antagonistic to the effects of IL-8.

PMID- 7738109
TI  - Association of vimentin intermediate filaments with the centrosome.
AB  - SW-13 cells that lack cytoplasmic intermediate filaments (IFs) were stably
      transfected with a human vimentin cDNA expression vector. Isolated subclones
      displayed two prevalent patterns of vimentin distribution as observed by indirect
      immuno-localization: (1) cytoplasmic filaments characteristic of a vimentin IF
      network; and (2) a distinct, juxtanuclear focus with limited filamentous
      extensions. Comparative analysis of two subclones that uniquely segregated these
      patterns of vimentin organization indicated that vimentin accumulated as a
      perinuclear focus in cells that expressed a 4-fold lower level of the protein.
      The observed variation in cellular organization was not due to detectable
      differences in vimentin protein modification, as determined by two-dimensional
      gel analysis. Increasing the amount of vimentin in a low expressing clone by a
      secondary transfection with human or mouse vimentin cDNA resulted in well
      dispersed, cytoplasmic filaments, suggesting that the distinct juxtanuclear
      organization of vimentin arose due to lower cellular vimentin levels. Employing
      anti-gamma-tubulin and anti-vimentin antibodies, dual immunofluorescence together
      with confocal microscopy revealed that the juxtanuclear focus of vimentin was
      located in the centrosomal region. Electron microscopy showed a spheroidal,
      filamentous structure with at least some filaments closely associated with the
      pericentriolar material (PCM). Because vimentin IF organization is at least
      partially dependent on microtubules, the effects of nocodazole and taxol on
      perinuclear vimentin foci were examined. Neither drug affected the juxtanuclear
      localization of foci, although taxol (10 microM, 5 hours) caused a release of
      pericentriolar gamma-tubulin from the nuclear region in 50-60% of the cells.
      These studies indicate that lower, in vivo, levels of vimentin fail to form
      extended IFs but rather are organized as a perinuclear aggregate. Moreover, the
      PCM of the centrosome appears to possess attachment sites for vimentin IFs.

PMID- 7738110
TI  - Stabilization and bundling of subtilisin-treated microtubules induced by
      microtubule associated proteins.
AB  - The acidic carboxy-terminal regions of alpha- and beta-tubulin subunits are
      currently thought to be centrally involved in microtubule stability and in
      microtubule association with a variety of proteins (MAPs) such as MAP2 and tau
      proteins. Here, pure tubulin microtubules were exposed to subtilisin to produce
      polymers composed of cleaved tubulin subunits lacking carboxy termini. Polymer
      exposure to subtilisin was achieved in buffer conditions compatible with further
      tests of microtubule stability. Microtubules composed of normal alpha-tubulin and
      cleaved beta-tubulin were indistinguishable from control microtubules with regard
      to resistance to dilution-induced disassembly, to cold temperature-induced
      disassembly and to Ca(2+)-induced disassembly. Microtubules composed of cleaved
      alpha- and beta-tubulins showed normal sensitivity to dilution-induced
      disassembly and to low temperature-induced disassembly, but marked resistance to
      Ca(2+)-induced disassembly. Polymers composed of normal alpha-tubulin and cleaved
      beta-tubulin or of cleaved alpha- and beta-tubulins were stabilized in the
      presence of added MAP2, myelin basic protein and histone H1. Cleavage of tubulin
      carboxy termini greatly potentiated microtubule stabilization by tau proteins. We
      show that this potentiation of polymer stabilization can be ascribed to tau
      induced microtubule bundling. In our working conditions, such bundling upon
      association with tau proteins occurred only in the case of microtubules composed
      of cleaved alpha- and beta-tubulins and triggered apparent microtubule cross
      stabilization among the bundled polymers. These results, as well as
      immunofluorescence analysis, which directly showed interactions between
      subtilisin-treated microtubules and MAPs, suggest that the carboxy termini of
      alpha- and beta-tubulins are not primarily involved in the binding of MAPs onto
      microtubules. However, interactions between tubulin carboxy termini and MAPs
      remain possible and might be involved in the regulation of MAP-induced
      microtubule bundling.

PMID- 7738111
TI  - Epithelial sorting of a glycosylphosphatidylinositol-anchored bacterial protein
      expressed in polarized renal MDCK and intestinal Caco-2 cells.
AB  - To evaluate whether a glycosylphosphatidylinositol (GPI) anchor can function as a
      protein sorting signal in polarized intestinal epithelial cells, the GPI
      attachment sequence from Thy-1 was fused to bacterial endoglucanase E' (EGE')
      from Clostridium thermocellum and polarity of secretion of the chimeric EGE'-GPI
      protein was evaluated. The chimeric EGE'-GPI protein was shown to be associated
      with a GPI anchor by TX-114 phase-partitioning and susceptibility to
      phosphoinositol-specific phospholipase C. In polarized MDCK cells, EGE' was
      localized almost exclusively to the apical cell surface, while in polarized
      intestinal Caco-2 cells, although 80% of the extracellular form of the enzyme was
      routed through the apical membrane over a 24 hour period, EGE' was also detected
      at the basolateral membrane. Rates of delivery of EGE'-GPI to the two membrane
      domains in Caco-2 cells, as determined with a biotinylation protocol, revealed
      apical delivery was approximately 2.5 times that of basolateral. EGE' delivered
      to the basolateral cell surface was transcytosed to the apical surface. These
      data indicate that a GPI anchor does represent a dominant apical sorting signal
      in intestinal epithelial cells. However, the mis-sorting of a proportion of
      EGE'GPI to the basolateral surface of Caco-2 cells provides an explanation for
      additional sorting signals in the ectodomain of some endogenous GPI-anchored
      proteins.

PMID- 7738112
TI  - Three microtubule-organizing centres collaborate in a mouse cochlear epithelial
      cell during supracellularly coordinated control of microtubule positioning.
AB  - Large cell surface-associated microtubule bundles that include about 3,000
      microtubules assemble in certain epithelial cells called inner pillar cells in
      the mouse organ of Corti. Microtubule-organizing centres (MTOCs) at both ends and
      near the middle of each cell act in concert during control of microtubule
      positioning. In addition, the three cell surface-associated microtubule
      organizing centres are involved in coordinating the connection of bundle
      microtubules to cytoskeletal components in neighbouring cells and to a basement
      membrane. The precisely defined locations of the three MTOCs specify the cell
      surface regions where microtubule ends will finally be anchored. The MTOCs are
      modified as anchorage proceeds. Substantial fibrous meshworks assemble at the
      surface sites occupied by the MTOCs and link microtubule ends to cell junctions.
      This procedure also connects the microtubule bundle to cytoskeletal arrays in
      neighbouring cells at two of the MTOC sites, and to the basilar membrane (a
      substantial basement membrane) in the case of the third site. A fourth meshwork
      that is not positioned at a major MTOC site is involved in connecting one side of
      the microtubule bundle to the cytoskeletons of two other cell neighbours. The
      term surfoskelosome is suggested for such concentrations of specialized
      cytoskeletal materials and junctions at cell surface anchorages for cytoskeletal
      arrays. The large microtubule bundle in each cell is composed of two closely
      aligned microtubule arrays. Bundle assembly begins with nucleation of
      microtubules by a centrosomal MTOC that is attached to the apical cell surface.
      These microtubules elongate downwards and the plus ends of many of them are
      apparently captured by a basal MTOC that is attached to the plasma membrane at
      the bottom of the cell. In the lower portion of the cell, the microtubule bundle
      also includes a basal array of microtubules but these elongate in the opposite
      direction. This investigation provides evidence that they extend upwards from the
      basal MTOC to be captured by a medial MTOC which is attached to the plasma
      membrane and situated near the mid-level of the cell. However, there are
      substantial indications that the basal array's microtubules are also nucleated by
      the apically situated centrosomal MTOC, but escape from it, and are translocated
      downwards for capture of their plus ends by the basal MTOC. If this is the case,
      then these microtubules continue to elongate after translocation and extend back
      up to the medial MTOC, which captures their minus ends.

PMID- 7738115
TI  - Novel tools for the study of development, migration and turnover of nematocytes
      (cnidarian stinging cells).
AB  - The rhodamine derivatives tetramethyl-rhodamine-5/6-maleimide (TROMI) and
      tetramethyl-rhodamine-6-isothiocyanate (TRITC) were allowed to react with living
      Hydra vulgaris. The two fluorescent dyes stain the polyps to different degrees,
      apparently without impairing their viability and behaviour. Concerning
      nematocytes, TROMI preferentially couples to cytoskeletal elements only of
      mounted nematocytes whereas TRITC selectively reacts with structural components
      of cysts of late nematoblasts, which thereafter develop apparently normally into
      mature nematocytes. Hence TROMI-labelling indicates that nematocytes are mounted
      and ready for discharge; TRITC-labelling can be used as a tool to investigate the
      final maturation, migration and installation of nematocytes in Hydra. Together
      with a new non-fixative method to dissociate Hydra polyps into single,
      identifiable cells, the two labelling methods allow direct quantitative dynamic
      studies of nematocyte turnover and open new possibilities of investigating the
      regulation and the mechanisms of nematocyte supply and migration.

PMID- 7738114
TI  - A mechanical function of myosin II in cell motility.
AB  - Myosin II mutant Dictyostelium amoebae crawl more slowly than wild-type cells.
      Thus, myosin II must contribute to amoeboid locomotion. We propose that
      contractile forces generated by myosin II help the cell's rear edge to detach
      from the substratum and retract, allowing the cell to continue forward. To test
      this hypothesis, we measured the speed of wild-type and myosin II null mutant
      Dictyostelium cells on surfaces of varying adhesivity. As substratum adhesivity
      increased, the speed of myosin II null mutant cells decreased substantially
      compared to wild-type cells, suggesting that the mutant is less able to retract
      from sticky surfaces. Furthermore, interference reflection microscopy revealed a
      myosin-II-dependent contraction in wild-type but not null mutant cells that is
      consistent with a balance of adhesive and contractile forces in retraction.
      Although myosin II null mutant cells have a defect in retraction, pseudopod
      extension does not cause the cells to become elongated on sticky surfaces. This
      suggests a mechanism, based possibly on cytoskeletal tension, for regulating cell
      shape in locomotion. The tension would result from the transmission of tractional
      forces through the cytoskeletal network, providing the myosin II null mutant with
      a limited means of retraction and cell division on a surface.

PMID- 7738113
TI  - A dialysis culture system for the study of the production and modulation of
      growth-regulatory molecules: studies using the P388D1 macrophage cell line.
AB  - P388D1 macrophage-like cells have previously been shown to produce both mitogenic
      and inhibitory regulators of porcine smooth muscle cell (pSMC) growth. The
      mitogenic activity was shown to have a molecular mass of > 10 kDa while the
      inhibitory activity was in the range of 2-6 kDa. In the present study, we present
      a novel dialysis culture system where P388D1 cells were grown in dialysis
      membranes with a 12 kDa cut-off which allowed continuous production of fractions
      of the culture medium. Using pSMC as target cells, mitogenic activity was found
      to be retained by the dialysis membrane while the low molecular mass inhibitory
      activity passed freely through the membrane. The effect of the macrophage
      activators phorbol myristate acetate (PMA), concanavalin A (ConA) and interferon
      gamma in combination with lipopolysaccharide (IFN gamma/LPS) were investigated in
      the dialysis culture system. PMA, ConA and IFN gamma/LPS were found to enhance
      the production of mitogenic activity by P388D1 cells. PMA also increased the
      production of growth-inhibitory activity, while ConA abolished inhibitor
      production and IFN gamma/LPS had no effect on the amount of inhibitory activity
      produced by P388D1 cells. The experiments show that the balance of production of
      mitogenic and inhibitory activities by macrophages can be modulated by agents
      that alter the state of activation of the cells. This could be of profound
      significance in the influence of macrophages on smooth muscle cell growth during
      the development of atherosclerosis.

PMID- 7738116
TI  - Developmental regulation of a protein kinase C isoform localized in the
      neuromuscular junction.
AB  - Protein kinase C (PKC) is a family of protein serine/threonine kinases consisting
      of multiple isoforms whose distinct physiological roles within cells are unknown.
      The message encoding the nPKC theta isoform, a member of the novel calcium
      independent class of PKCs, has recently been shown to be abundant in mouse
      skeletal muscle. The message for cPKC alpha, a calcium-dependent isoform, was
      also found to be highly expressed in this tissue. In an effort to distinguish
      between the physiological roles of these two isoforms of PKC in rat skeletal
      muscle, we examined their subcellular distribution, developmental expression and
      intracellular localization. We generated an isotype-specific antiserum directed
      against a peptide sequence unique to nPKC theta. This antiserum recognized a 79
      kDa protein highly enriched in rat skeletal muscle, which is likely to be nPKC
      theta. cPKC alpha was also readily detectable in skeletal muscle, using another
      isotype-specific antibody, but it appeared to be ubiquitously expressed in all of
      the tissues we examined. Together these results suggest that nPKC theta, rather
      than cPKC alpha, is involved in physiological functions that are specific for
      skeletal muscle. The immunoreactivity for nPKC theta was highest in the membrane
      subcellular fraction compared to the cytosolic fraction of skeletal muscle. In
      contrast, cPKC alpha was found to be predominantly distributed in the cytosolic
      rather than the membrane fraction. nPKC theta appeared to be developmentally
      regulated postnatally in rat skeletal muscle, with a 4-fold increase in
      expression occurring exclusively in the membrane fraction during postnatal days 3
      through 21. This time course coincides with the period in rat development
      associated with maturation of neuromuscular junctions. Expression of nPKC theta
      in rat spleen, another tissue expressing detectable levels of this isoform, was
      not found to be developmentally regulated during this time. cPKC alpha expression
      was found to increase slightly from postnatal days 3 through 11 and no
      developmental increase in expression of this isoform was observed in skeletal
      muscle during postnatal days 11 through 21. The intracellular localization of the
      PKC theta and alpha isoforms in rat skeletal muscle was examined by
      immunocytochemistry. nPKC theta was detected in association with the sarcolemma
      of skeletal muscle and was found to be localized in the neuromuscular junction.
      Enhanced staining for nPKC theta in the neuromuscular junction appeared as early
      as postnatal day 4 during development. Staining for nPKC theta in the
      neuromuscular junction persisted after prolonged denervation, suggesting that the
      enzyme is distributed postsynaptically.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7738117
TI  - Utrophin actin binding domain: analysis of actin binding and cellular targeting.
AB  - Utrophin, or dystrophin-related protein, is an autosomal homologue of dystrophin.
      The protein is apparently ubiquitously expressed and in muscle tissues the
      expression is developmentally regulated. Since utrophin has a similar domain
      structure to dystrophin it has been suggested that it could substitute for
      dystrophin in dystrophic muscle. Like dystrophin, utrophin has been shown to be
      associated with a membrane-bound glycoprotein complex. Here we demonstrate that
      expressed regions of the predicted actin binding domain in the NH2 terminus of
      utrophin are able to bind to F-actin in vitro, but do not interact with G-actin.
      The utrophin actin binding domain was also able to associate with actin
      containing structures, stress fibres and focal contacts, when microinjected into
      chick embryo fibroblasts. The expressed NH2-terminal 261 amino acid domain of
      utrophin has an affinity for skeletal F-action (Kd 19 +/- 2.8 microM), midway
      between that of the corresponding domains of alpha-actinin (Kd 4 microM) and
      dystrophin (Kd 44 microM). Moreover, this utrophin domain binds to non-muscle
      actin with a approximately 4-fold higher affinity than to skeletal muscle actin.
      These data (together with those of Matsumura et al. (1992) Nature, 360, 588-591)
      demonstrate for the first time that utrophin is capable of performing a
      functionally equivalent role to that of dystrophin. The NH2 terminus of utrophin
      binds to actin and the COOH terminus binds to the membrane associated
      glycoprotein complex, thus in non-muscle and developing muscle utrophin performs
      the same predicted 'spacer' or 'shock absorber' role as dystrophin in mature
      muscle tissues. These data suggest that utrophin could replace dystrophin
      functionally in dystrophic muscle.

PMID- 7738118
TI  - Inositol 1,4,5-trisphosphate receptor-like protein in plasmalemmal caveolae is
      linked to actin filaments.
AB  - We reported that a plasmalemmal inositol 1,4,5-trisphosphate receptor-like
      protein (PM InsP3R-L) is localized in caveolae of various non-neuronal cells in
      vivo (Fujimoto et al. (1992) J. Cell Biol. 119, 1507-1513). In the present study,
      we investigated the distribution of PM InsP3R-L in cultured cells. In mouse
      epidermal keratinocytes (Pam 212) cultured in standard Ca2+ (1.8 mM), PM InsP3R-L
      was distributed densely in the vicinity of cell-to-cell contacts. In contrast,
      when Pam cells were cultured in low Ca2+ (0.06 mM) without making cell-to-cell
      contacts, PM InsP3R-L was observed randomly; by restoring the Ca2+ concentration,
      the circumferential actin filaments became obvious and the density of PM InsP3R-L
      increased in the contact region. Treatment of Pam cells with cytochalasin D
      caused aggregation of caveolae where PM InsP3R-L as well as F-actin and fodrin
      were localized. In bovine aortic endothelial cells, PM InsP3R-L was aligned along
      actin filaments crossing the cytoplasm in various directions. PM InsP3R-L of Pam
      cells was hardly extracted by treatment with 0.5% Triton X-100 or 60 mM octyl
      glucoside in a cytoskeleton-stabilizing buffer for 15 minutes at 4 degrees C. The
      results show that the distribution of caveolae bearing PM InsP3R-L changes when
      the actin cytoskeleton is modified. They also indicate that the association of PM
      InsP3R-L with actin filaments may mediate the redistribution of caveolae. Since
      caveolae are thought to be related to signal transduction, their location defined
      by the actin cytoskeleton may affect the site where cellular reaction is to occur
      in response to various stimuli.

PMID- 7738119
TI  - Expression and localization of annexin VII (synexin) in muscle cells.
AB  - Annexin VII (synexin) is a member of the annexin family of proteins, which are
      characterized by Ca(2+)-dependent binding to phospholipids. We used PCR to
      isolate from a lambda gt11-mouse fibroblast library annexin VII cDNA fragments
      corresponding to the two isoforms found in both humans and Dictyostelium
      discoideum. The two isoforms of 47 kDa and 51 kDa differed by 22 amino acids
      inserted into the proximal third of the hydrophobic N terminus. Annexin VII
      specific polypeptides expressed in Escherichia coli were used to generate isoform
      specific monoclonal antibodies. Expression of the two isoforms during myogenesis
      was followed in the myogenic cell lines BC3H1 and L6. Only the 47 kDa isoform was
      present in undifferentiated L6 or BC3H1 myoblasts. The 51 kDa isoform appeared
      after myogenesis had been induced and in striated muscle only the 51 kDa isoform
      was observed. Immunofluorescence showed that annexin VII was located in the
      cytosol of mononucleated and fused polynucleated cultured cells, whereas in
      striated muscle, annexin VII was located preferentially at the plasma membrane
      and the transverse tubules. However, there was also some residual cytosolic
      staining, which was more abundant in type II (fast twitch) than in type I (slow
      twitch) fibers. Permeabilization of L6 cells with digitonin in the presence of 5
      mM EGTA led to a release of annexin VII from the cells, which paralleled the loss
      of cytosolic lactate dehydrogenase (LDH) at low detergent concentrations (50
      microM). In the presence of 100 microM extracellular Ca2+, annexin VII remained
      bound to the plasma membrane even in the presence of high digitonin
      concentrations. Incubation with the Ca(2+)-specific ionophore A23187 and 100
      microM extracellular Ca2+ led to a redistribution of annexin VII from the cytosol
      to the plasma membrane after 30 minutes of incubation. The results obtained
      indicate a developmentally and Ca(2+)-regulated localization and expression of
      annexin VII and raise the possibility that annexin VII may play a role in
      excitation-contraction coupling in skeletal muscle.

PMID- 7738120
TI  - Identification of the cells expressing cot proto-oncogene mRNA.
AB  - The cell types expressing cot proto-oncogene mRNA were identified by in situ
      hybridization (ISH) histochemistry. Among a variety of adult mouse tissues
      examined, four types of glandular cells expressing cot gene were identified: (1)
      granular duct cells in the submandibular and sublingual glands; (2) serous cells
      in the parotid gland; (3) peptic (chief) cells in gastric glands; and (4) goblet
      cells in colonic glands. Investigation of the developmentally regulated
      expression of cot mRNA using tissues of 14-day and 18-day embryos, newborn and
      weanling mice showed that cot gene is expressed only in morphologically
      differentiated and functionally activated cells of these four types. No other
      types of cells showing ISH signals were observed. Based on these results, cot
      gene expressions in cultured cells of colonic adenocarcinomas and gastric
      adenocarcinomas were examined. SW 480 and WiDr cells showed high expression of
      this gene and so should be useful for functional analysis of Cot kinase. The
      expression patterns of cot gene in tumor tissues of the parotid gland, and
      gastric and colonic glands were investigated. Two of the tissues overexpressed
      this gene markedly, suggesting that overproduction of Cot kinase may be one cause
      of their transformation.

PMID- 7738121
TI  - [Epidural hematoma. Myth and reality, based on 3 exemplary cases].
AB  - The acute epidural hematoma is a real surgical emergency with a good outcome if
      the operation is performed in reasonable delays. In 1994, too many young patients
      eventually died or were left with major disabilities, because of an unacceptable
      and almost always avoidable loss of time. We do emphasize some rules which have
      to be followed to avoid catastrophic events.

PMID- 7738122
TI  - [A case of pure unilobar Caroli disease].
AB  - We describe a new case of pure Caroli disease and review of the literature.
      Although often sporadic, this disease is usually considered an autosomal
      recessive hereditary disease. It is often either associated with another
      congenital hepatorenal fibrocystic disease or with extrahepatic bile duct
      dilatation. The clinical examination and laboratory tests are of not specific if
      congenital hepatic fibrosis or congenital cysts of the coleduct is lacking.
      Certain echographic and scan images are however very specific. Complications are
      related to intrahepatic stone formation and to superinfections. The long-term
      course appears to involve increased risk of cholangiocarcinoma. Treatment of the
      localized form includes priority resection. In diffuse disease, treatment may be
      more medical with antibiotics and sometimes bile solvents. In case of failure,
      transplantation may be entertained.

PMID- 7738123
TI  - [Intraoperative colonic irrigation in the emergency treatment of occlusive
      lesions of the left colon].
AB  - This study reports the use of an intraoperative antegrade colonic irrigation in
      the management of left-sided large bowel obstruction requiring emergency surgery.
      35 consecutive patients had primary bowel resection with immediate anastomosis
      (without colostomy) after intraoperative antegrade colonic irrigation. The cause
      of the obstruction was large bowel carcinoma in 26, diverticulitis in seven and
      volvulus in two cases. There were two post-operative deaths (5.7%). No digestive
      fistula was observed. The results of this study suggest that intraoperative
      colonic irrigation is an effective method, enabling the surgeon to perform a
      primary anastomosis with reasonable safety after emergency resection of selected
      distal colonic lesions.

PMID- 7738124
TI  - [Video-assisted thoracic surgery of hydatid cysts of the lung in children].
AB  - 10 children between 3 and 9 years old, have been operated on for an
      echinococcosis cyst of the lung, by a thoracoscopic procedure. It was a vomited
      cyst in 6 cases, a pyopneumocyst in 1 case, and a jung noncomplicated and
      univesicular cyst in 3 cases. The surgical procedure is described. We brought
      into being the operative conditions such it is nowadays an excellent alternative
      to the classical thoracotomy.

PMID- 7738125
TI  - [Intraoperative pulmonary embolism of a hydatid membrane].
AB  - Only four cases of per-operative pulmonary embolus of parasites during surgery
      for hydatic cysts of the liver have been reported. Embolus usually occurs in
      patients who already have lung metastasis of hepatic cysts, suggesting a hepatic
      cyst in direct communication with the vena cava or suprahepatic vein. We report
      the first case which occurred in a patient in which there was no evidence of such
      communication.

PMID- 7738126
TI  - [Trans-sutural mechanical anastomosis in esophagogastric surgery. Apropos of 25
      cases].
AB  - The essential point conditioning the success of a mechanical esophagogastric or
      esophagojejunal anastomosis is the performance of an esophageal purse. The
      authors present a variety of the technique which consists of replacing the
      esophageal purse by a linear stapling after having introduced the anvil in
      esophagus. The anvil shaft is then exteriorized through the staple line. From
      January 1991 to January 1994, this technique was performed on 25 patients (17 men
      and 8 women), with a mean-age of 66 years (range 27 to 83). The esophagojejunal
      anastomosis after total gastrectomy was performed on 17 patients (15 carcinomas,
      1 acute gastritis with gastric haemorrhage, 1 stomal ulcer), and the
      esophagogastric anastomosis after partial esophagectomy for carcinoma on 8
      patients. After six to twelve months neither an anastomotic stenosis nor a
      leakage occurred. The advantage of this technique is on one hand to simplify the
      performance of the anastomosis and to reduce the septic and operating time, on
      the other hand to avoid the complications of performing the esophageal purse.

PMID- 7738127
TI  - [Preoperative localization of asymptomatic breast lesions by the technique of
      stereotaxic tattooing and use of a wire. Apropos of 670 cases].
AB  - OBJECTIVE: To compare the quality of pre-operative analysis of sub-clinical
      lesions of the breast using a wire and stereotaxic tattooing. METHODS: Between
      1983 en 1990, 670 cases were analysed. At first needle or wire localisation
      techniques were used and then from 1988 onwards stereotaxic tattooing, first with
      the wire technique combined with it and later by itself from 1989 onwards. PLACE
      STUDY CARRIED OUT: Oscar-lambret Centre in the Department of Surgery and
      Radiodiagnosis I, BP 307, Lille Cedex. RESULTS: 190 carcinomas were diagnosed
      (30.7%) of which 20 were micro-invasive and 46 carcinoma in situ. The efficiency
      of the analysis was evaluated according to the number of explorations that were
      necessary to remove healthy tissue around the lesion. The wire technique results
      were significantly different (15.43% = 339 cases), tattooing with wire (9.13% =
      144 cases), and tattooing by itself (6.30% = 135 cases). CONCLUSION: It seems
      that pre-operative assessment using stereotaxic tattooing is the most reliable of
      methods because it allows limited excision of the lesion and a more aesthetic
      approach.

PMID- 7738128
TI  - [Treatment of endoscopic colonic perforations by anastomosis in non exclusive
      lateral colostomy].
AB  - The authors report two cases of colonic endoscopic perforation with peritonitis
      treated by minimal lateral colostomy. The evolution was favorable in this two
      cases with spontaneous closure of colostomy. We intended to remind the usefulness
      of this old and simple technique sometimes omitted in the therapeutic armentorium
      of the iatrogenic colic perforation, especially from endoscopic origin. Thus the
      risk of complications of an ideal surgery or the necessity of a second-time
      anastomosis after the initial colostomy can be avoided.

PMID- 7738129
TI  - [Differed autologous blood transfusion in the "G" point hospital in Bamako.
      Prospective study apropos of 40 cases].
AB  - With a sample of 40 patients, the authors conducted a prospective case-control
      study on the feasibility of differed autologous blood transfusion at Point "G"
      National Hospital in Bamako, Mali. The method has been accepted by all the
      patients. No clinical nor biological trouble has been reported by the patients
      themselves. The authors recommend the use of autologous blood transfusion by
      other hospital units and the development of regulations governing its
      implementation.

PMID- 7738130
TI  - [Differed autologous blood transfusion and its effects during pulmonary
      lobectomy].
AB  - The aim of our study was to determine the value of preoperative autologous blood
      donation and its importance with regard to pulmonary lobectomies. Over the course
      of three years and a total number of 220 operations, autologous blood was
      preoperatively deposited in 74 cases. 21 patients did not meet the criteria for
      autologous blood donation and were excluded from the study. It was found that
      only 6.8% of the patients who had donated autologous blood required a homologous
      blood transfusion versus 27.2% in the non-donor group. This would imply, that the
      necessity for homologous blood transfusion is reduced by approximately 75% in
      patients depositing autologous blood prior to surgery. While we observed similar
      haemoglobin levels in both groups at admission, it was found that autologous
      blood donors went into surgery with an Hb 1.5 g% lower than non donors; the
      levels however adjusted themselves immediately postoperatively. No increased
      complication rate was found as a result of preoperative autologous blood
      donation. The data indicate that only 30% of patients undergoing pulmonary
      lobectomy require homologous blood transfusions. 80% of these patients could
      benefit from preoperative autologous blood donation. For 70% of all patients the
      procedure would be of no benefit. Bearing in mind the immunosuppressive effect of
      homologous blood transfusions, which may result in a higher rate of tumor
      recurrence, we find preoperative autologous blood donation a justifiable
      procedure even under these circumstances. It would however be beneficial if
      studies were conducted to investigate to what extent similar results could be
      achieved by preoperative acute isovolemic hemodilution.

PMID- 7738131
TI  - [The styloid bone and carpal protuberance].
AB  - Dorsal carpal protuberance of the wrist is frequently caused by the presence of a
      styloideum bone. We report a case illustrating this pathophysiological
      hypothesis. This pathology is often confused with synovial cyst emphasizing the
      importance of a lateral view of the hand in 30 degrees supination. Computed
      tomography sections are also helpful showing the exact nature of the
      protuberance. A cuneiform resections of the joint line can leave to complete
      symptom relief.

PMID- 7738132
TI  - [Operative risk in thoracic surgery].
AB  - Operative risk is encountered daily in thoracic surgery. Preoperatively, the risk
      can be evaluated by the pneumologist as well as the intensive care-surgery team.
      The parenchymal function and the patients respiratory capacity during the post
      operative period should be evaluated. It is fundamental to evaluate heart
      function and vascular capacity. We discuss operative risk of dissection. The risk
      of bronchial fistulization is estimated at 5% (pneumonectomy) and 1% (lobectomy).
      Immediate complications include air leaks, rhythm disorders and post-operative
      bleeding. Thoracic drainage is a determining factor in thoracic surgery. The main
      problem remains post-operative respiratory failure especially since
      carcinological exeresis is usually carried out in patients with bronchopathies.

PMID- 7738133
TI  - [Medicolegal aspects in surgery of varicose veins].

PMID- 7738135
TI  - The determination of allantoin, a possible indicator of oxidant status, in human
      plasma.
AB  - Because uric acid may be oxidized to allantoin by various reactive oxygen
      species, it is postulated that uric acid functions as an antioxidant in human
      bodily fluids. The measurement of allantoin concentrations may therefore be
      useful for the quantitation of oxidant generation in humans. We develop a
      reliable assay for the quantitation of human plasma allantoin levels. The method
      consists of rapid and selective separation of allantoin from uric and glyoxylic
      acid (which interfere in the assay) using anion-exchange solid-phase extraction
      prior to conversion of allantoin to glyoxylic acid and derivatization with 2,4
      dinitrohenylhydrazine. Determination of glyoxylate-2,4-dinitrophenylhydrazone is
      achieved by using reversed-phase high-performance liquid chromatography with
      gradient elution and ultraviolet detection at 360 nm. The analytical performance
      of the method is satisfactory, with a day-to-day coefficient of variation of 8.9%
      and a within-batch coefficient of variation of 7.2%. The method is applied to the
      measurement of allantoin concentrations in the plasma of 99 apparently healthy
      men, and a preliminary reference range is reported. Clinical studies can now be
      performed to evaluate allantoin as a possible indicator of free radical damage in
      vivo.

PMID- 7738134
TI  - Analysis of fluorescently labeled sugars by reversed-phase ion-pairing high
      performance liquid chromatography.
AB  - Reducing sugars, including monosaccharides, disaccharides, and a trisaccharide,
      are derivatized by reductive amination with 7-amino-1,3-naphthalene disulfonic
      acid. Reversed-phase ion-pairing high-performance liquid chromatography is then
      used to separate these visibly fluorescent, charged conjugates. Isocratic elution
      with triethylamine-acetic acid from a phenyl column, a C18 column, and C18 and
      phenyl columns in series gives good separations of a mixture of monosaccharides
      and a mixture of disaccharides and trisaccharides. Resolution of certain
      monosaccharides is enhanced by replacing triethylamine with a chiral amine and
      using gradient elution. Further enhancement of resolution is achieved by adding
      phenylboronic acid, an agent capable of complexing with the vicinal diol
      functionality present in many sugars. The trimethylamine-acetic acid eluant
      permits detection by either ultraviolet absorbance or fluorescence, and the
      addition of a chiral ion-pairing agent or a phenylboronic acid complexing agent
      necessitates fluorescence detection. A reversible Schiff base form of the
      fluorescent sugar conjugate is prepared; it is sufficiently stable to perform
      fractionations but sufficiently unstable to be converted to a fluorescent label
      and reducing sugar.

PMID- 7738136
TI  - The detection of varicella zoster antibodies by simultaneous competitive EIA and
      its comparison with radioimmunoassay, latex agglutination and antiglobulin type
      EIA.
AB  - A rapid and simultaneous competitive enzyme immunoassay (EIA) for the detection
      of human antibodies to varicella zoster virus (VZV) which utilises complement
      fixing (CF) VZV antigen and peroxidase labelled human antibodies to VZV as
      reagents is described. The competitive EIA was compared with competitive
      radioimmunoassay (RIA) in a selection of sera from 501 blood donors and 115
      patients. The competitive EIA was comparable in sensitivity and specificity to
      the RIA, but had the advantage of not requiring radiolabelling or facilities for
      radioactive handling and disposal, and also had an enhanced stability. The
      competitive EIA was compared with competitive RIA, a commercially available latex
      agglutination assay and an antiglobulin type EIA on sera from 100 patients. The
      competitive EIA and RIA appeared to be the most sensitive tests.

PMID- 7738137
TI  - Hepatitis C virus RNA detection and HCV genotype in patients with chronic non-A,
      non-B hepatitis in Jakarta.
AB  - Antibody response in HCV infection may be variable and the variability of the
      serological response could be due to the differences in HCV strains. Since the
      distribution of hepatitis C virus genotype has been found to be geographically
      dependent, it is important to determine the distribution of HCV genotype in
      various countries with high prevalence of chronic non-A, non-B hepatitis. In this
      study, serum HCV RNA was examined in 53 patients suspected of chronic non-A, non
      B hepatitis with an anti-HCV test as determined by currently available assay. HCV
      viremia was detected in 48 patients (90.6%). These patients had elevated serum
      ALT level at the time of HCV RNA determination. Using specific genotype probes,
      all isolates were classified into three different genotypes. Double and triple
      infections were also noted. HCV genotype 1b is the predominant genotype found in
      chronic hepatitis C patients in Jakarta.

PMID- 7738138
TI  - Use of lactate dehydrogenase to evaluate the anti-viral activity against
      influenza A virus.
AB  - The detection of lactate dehydrogenase (LDH) can be used to evaluate efficiently
      anti-influenza A virus agents. LDH levels in the virus-infected Madin-Darby
      canine kidney cell cultures were significantly higher than in controls, were in
      proportion to the degree of virus infection, and corresponded to a decrease in
      mitochondrial dehydrogenase activity as assayed using a tetrazolium colorimetric
      assay (MTT method). The EC50 value and cytotoxicity of ribavirin, 3-deazaguanine,
      pyrazofurin, and carbodine against influenza A virus as measured by the LDH
      detection method was equivalent to that derived by the MTT method.

PMID- 7738139
TI  - Rapid, single-step RT-PCR typing of dengue viruses using five NS3 gene primers.
AB  - In order to detect and type dengue viruses in serum specimens, four type-specific
      downstream primers were designed for use with a consensus upstream primer in a
      reverse transcription and polymerase chain reaction (RT-PCR) assay. RT-PCR using
      these five primers amplified NS3 gene fragments of diagnostic sizes of 169, 362,
      265 and 426 base pairs for dengue virus types 1, 2, 3 and 4, respectively, but
      not for Japanese encephalitis, Kunjin and yellow fever viruses. The conventional
      two-step RT-PCR procedure was simplified by combining RT and PCR in a single-step
      format with a "hot start". This RT-PCR protocol was applied successfully to
      dengue virus-spiked serum and dengue patient serum samples, and could detect as
      few as one PFU of dengue virus. This assay offers a rapid, specific and sensitive
      molecular technique for the simultaneous detection and typing of dengue viruses.

PMID- 7738140
TI  - Immunodominant epitopes on the NS1 protein of MVE and KUN viruses serve as
      targets for a blocking ELISA to detect virus-specific antibodies in sentinel
      animal serum.
AB  - Two mosquito-borne flaviviruses, Murray Valley encephalitis (MVE) and Kunjin
      (KUN), are the aetiological agents of Australian encephalitis. MVE causes a
      severe and potentially fatal form of the disease while KUN is responsible for
      only a few relatively mild cases. Therefore it is important that serological
      tests used in flavivirus surveillance differentiate between infections with these
      two viruses. However, this has been hampered in the past by the close antigenic
      relationships between flaviviruses in traditional serological assays. An epitope
      blocking ELISA using MVE-specific and KUN-specific monoclonal antibodies (mAb)
      reacting to the non-structural protein NS1 of these viruses and a flavivirus
      group-specific mAb reacting to the envelope (E) protein was assessed for testing
      sentinel animals for seroconversion to specific flavivirus infections. Using
      these assays we were able to detect serum antibodies to a variety of flavivirus
      in laboratory infected rabbits, and naturally infected chickens and in the case
      of primary infections, differentiate those caused by KUN or MVE. These assays are
      now used routinely in our laboratory for testing chicken sera from sentinel
      flocks in the Kimberley and Pilbara regions of north Western Australia.

PMID- 7738141
TI  - Differentiation of cognate dsRNA genome segments of bluetongue virus reassortants
      by temperature gradient gel electrophoresis.
AB  - The analysis of reassortant viruses has been a valuable tool in the investigation
      of protein interaction and function in double-stranded (ds) RNA virus research.
      The differentiation of cognate dsRNA genome segments of reassortants is
      conventionally achieved by SDS-polyacrylamide gel electrophoresis (SDS-PAGE).
      However, due to a high degree of sequence homology among different bluetongue
      virus (BTV) serotypes, it is not uncommon to find that certain cognate dsRNA
      segments cannot be differentiated by SDS-PAGE. Temperature gradient gel
      electrophoresis (TGGE) has been shown to be a much more sensitive method of
      differentiating RNA or DNA fragments of high sequence homology. Here we report
      the preliminary application of TGGE in analysis of genomic reassortants of two
      BTV serotypes, 1 and 23. While six out of ten genome segments between BTV-1 and
      BTV-23 could not be resolved by SDS-PAGE, all of them were differentiated by
      TGGE. The ability of TGGE to distinguish between dsRNA segments of high sequence
      homology may also make it useful in the search for BTV genes responsible for
      defined characteristics, such as virulence, by differentiating wild-type and
      mutated gene segments of viruses displaying altered phenotypes.

PMID- 7738142
TI  - Analysis of immunoassays to detect antibodies to hepatitis A virus (anti-HAV) and
      anti-HAV immunoglobulin M.
AB  - Two newly developed anti-HAV tests were assessed, using a total of 1835 sera.
      These two tests are being distributed under the trademarks Enzymun-Test anti-HAV
      and Enzymun-Test IgM anti-HAV. The anti-HAV test was compared to anti-HAV tests
      from other manufacturers and featured a high sensitivity combined with a high
      level of reproducibility and specificity. In terms of sensitivity,
      reproducibility and specificity, the IgM test proved to be comparable to other
      IgM anti-HAV tests used for the diagnosis of acute type A hepatitis. Combining
      both tests was shown to be useful to recognize an acute or past hepatitis A virus
      infection. In addition, the high sensitivity of the anti-HAV test makes this test
      extremely useful to assess the immunoresponse to the hepatitis A vaccine.

PMID- 7738143
TI  - The development of PCR based assays for the detection and differentiation of
      simian immunodeficiency virus in vivo.
AB  - Polymerase chain reaction based assays, which amplify a region of the gag gene,
      have been developed for the direct detection of simian immunodeficiency virus
      (SIV) DNA sequences in the blood of experimentally infected cynomolgus macaques.
      In macaques infected with a characterised virus pool (11/88 pool SIVmac 32H), an
      assay employing a single round of amplification was found to be highly sensitive
      and specific. However, in animals infected with the SIV molecular clones J5 and
      C8 (Rud et al., J. Gen. Virol. 75, 529-543), it was necessary to use two rounds
      of amplification and nested primer pairs in order to achieve sensitivity > 90%.
      In order to differentiate macaques infected with either of the two genetically
      distinct SIV clones, J5 or C8, a third PCR based assay has been developed, which
      amplifies a 492 bp region of the nef gene. Sequence differences between the nef
      genes of the two molecular clones enabled the PCR product amplified from each
      virus to be distinguished by restriction analysis. These sensitive and specific
      assays complement virological detection of SIV and enable superinfection studies
      to be evaluated; a prerequisite for the testing of live attenuated
      immunodeficiency virus vaccines.

PMID- 7738144
TI  - Value of a new rapid non-radioactive sequencing method for analysis of the
      cytomegalovirus UL97 gene in ganciclovir-resistant strains.
AB  - Various DNA changes located within a restricted region of the UL97 open reading
      frame were shown to be associated with the resistance of cytomegalovirus strains
      to ganciclovir (GCV). In order to analyse this UL97 region in sensitive and GCV
      resistant strains, a non-radioactive sequencing assay (Promega, Madison, WI, USA)
      which combines the dideoxy visualisation by silver-staining of the gel was used.
      Using this assay, polymerase chain reaction products from results were obtained
      within 1 day. Point mutations modifying the amino acid sequence of the putative
      UL97 catalytic site were detected in three isolates. These led to an alanine to
      valine substitution in residue 594 in one strain with reduced GCV sensitivity,
      and to a cysteine to glycine substitution in residue 592 in two GCV-resistant
      isolates. These mutations were different from the DNA changes previously mapped
      in GCV-resistant laboratory or field strains. No amino acid substitution in the
      UL97 catalytic site was found in GCV-sensitive isolates. Transfer marker
      experiments are in progress in order to test the significance of these DNA
      changes for GCV resistance. This rapid non-radioactive sequencing protocol could
      be a useful tool for analysing the UL97 region encoding the putative UL97
      catalytic site of clinical isolates.

PMID- 7738146
TI  - A non-radioactive multiprime sequencing method for HIV genomes.
AB  - A manual non-radioactive DNA sequencing protocol was developed for rapid analysis
      of variable HIV-1 genomes. Sets of up to ten primers were used in one sequencing
      reaction. After polyacrylamide gel electrophoresis and blotting onto nylon
      membranes the individual sequences were detected by hybridization with
      digoxigenin-labelled oligonucleotides and chemiluminescence. The method is
      applicable to any sequencing project where numerous variants of DNA fragments of
      several 1000 bp of length are to be analysed.

PMID- 7738145
TI  - Analysis of enterovirus genotypes using single-strand conformation polymorphisms
      of polymerase chain reaction products.
AB  - Enterovirus genotypes were identified rapidly by reverse (RT-PCR) followed by
      single-strand conformation polymorphism (SSCP) analysis. The primer pair was
      chosen from the highly conserved sequence at the 5' non-coding region of
      enterovirus genomes. RT-PCR amplified a 154 bp sequence in all samples from 14
      serotypes of enteroviruses, including group A and B Coxsackie viruses,
      echoviruses and polioviruses. SSCP analysis of these products revealed different
      electrophoretic profiles. Thus, SSCP analysis will be useful for differentiating
      the genotypes of enteroviruses, and may be applicable for rapid diagnosis of
      enteroviral infection.

PMID- 7738147
TI  - Differentiation between glycoprotein III gene-deleted vaccine and wild-type
      strains of pseudorabies virus by polymerase chain reaction (PCR).
AB  - One of the attenuated and genetically recombinant modified-live viral (MLV)
      vaccine strains currently used contains a deletion in its glycoprotein III (gIII)
      gene, while prototypic wild-type pseudorabies (WT-PR) viruses contain an intact
      gIII gene. A polymerase chain reaction (PCR) system differentiating, based on
      this difference, between the vaccine virus and prototypic WT-PR viruses was
      investigated. This PCR system utilized two consecutive stages. Primers for the
      first-stage PCR were designed so as to amplify of DNA fragments lengths in
      respect to the vaccine and WT-PR viruses. The second-stage PCR amplification for
      improving the sensitivity and specificity and for confirming of the sites deleted
      from the first-stage PCR products produced an all-or-none result: internal DNA
      fragments were derived from only WT-PR viruses but not from the vaccine virus.
      These PCR-amplified fragment length polymorphisms clearly distinguished the
      vaccine virus from WT-PR viruses. The vaccine and WT-PR viruses in mixtures were
      each identified in this PCR system. This PCR system may permit rapid and
      sensitive detection of PR viral gIII gene, analysis of the genotype of PR virus
      isolates, and also examination of the isolates for purity and identity.

PMID- 7738148
TI  - Detection of hepatitis B and woodchuck hepatitis viral DNA in plasma and
      mononuclear cells from heparinized blood by the polymerase chain reaction.
AB  - Amplification by the polymerase chain reaction (PCR) of hepatitis B virus (HBV)
      DNA extracted from parallel samples of serum and heparinized plasma gave
      contradictory results, indicating that heparin inhibits virus detection.
      Similarly, analysis of PCR products of woodchuck hepatitis virus (WHV) DNA showed
      that heparinization of blood abolished WHV DNA amplification, while
      anticoagulation with sodium EDTA or acid citrate dextrose did not. Amplification
      of recombinant WHV and HBV DNA in the presence of increasing concentrations of
      sodium heparin progressively inhibited and finally abolished virus genome
      detection. The inhibitory effect of heparin was reversed by treatment of either
      plasma or isolated DNA with heparinase (5 U/reaction, 1 h at 28 degrees C) prior
      to PCR. In contrast, heparin did not influence the detection of hepadnavirus in
      peripheral blood mononuclear cells (PBMC), even after prolonged incubation of the
      cells with heparin in culture. These findings confirm that heparin exerts a
      dramatic inhibitory effect on hepadnaviral DNA detection by PCR and they
      demonstrate that this effect can be reversed by heparinase. The findings also
      show that extensively washed PBMC derived from heparinized blood can be a
      reliable source of nucleic acids for amplification of hepadnavirus genome. These
      results imply that previous data should be reassessed if samples of heparinized
      plasma were found hepadnavirus DNA nonreactive by PCR or when these samples were
      used as a starting material for PCR quantitation of viral genome.

PMID- 7738149
TI  - Selection of a monoclonal antibody specific for variant B human herpesvirus 6
      infected mononuclear cells.
AB  - A monoclonal antibody, designated as MAb 6E2, specific for human herpesvirus 6
      variant B (HHV-6B) was derived from the spleen of a mouse immunized with lysates
      of HHV-6B(Z29) cord blood mononuclear cells. MAb 6E2 reacts by immunofluorescence
      with all the HIV-6B strains tested (Z29, CV, Hashimoto and SF) and fails to react
      with variant A prototypes, GS and U1102. The immunofluorescence staining was
      punctate and localized to the cytoplasm. The protein reacting with MAb 6E2 was
      identified as protein 48,000 in apparent M(r) value by immunoaffinity
      chromatography of lysates of HHV-6B-infected mononuclear cells.

PMID- 7738150
TI  - Molecular cloning of Indian tomato leaf curl virus genome following a simple
      method of concentrating the supercoiled replicative form of viral DNA.
AB  - DNA-A and DNA-B components of the genome of a whitefly transmitted virus causing
      yellowing and leaf curl in tomato (ITLCV) were cloned following a simple
      procedure for isolation of the double stranded replicative form of viral DNA from
      infected tomato plants. The method is based on extraction of total DNA from
      infected plants followed by concentration of the double stranded replicative form
      of viral DNA by an alkaline denaturation procedure identical to that used for
      isolation of plasmid DNA from Escherichia coli. The attempted cloning of DNA
      showed that 95% of the transformants contained plasmids with an insert of either
      DNA-A (2.75 kb) or DNA-B (2.55 kb). Cloned DNA-A and DNA-B when used as probes
      could detect DNA-A/DNA-B in total nucleic acid obtained from fresh diseased
      tissue. Both DNA-A and DNA-B are needed for infection and they have a common
      region of 166 bases with about 94% nucleotide sequence homology, a characteristic
      of all bipartite geminiviruses. Comparison of the amino acid sequence of the
      putative coat protein product of ITLCV with some other mono- and bipartite
      geminiviruses revealed a maximum of 86% homology with Indian cassava mosaic
      virus.

PMID- 7738151
TI  - Standardisation of primers and an algorithm for HIV-1 diagnostic PCR evaluated in
      patients harbouring strains of diverse geographical origin. The Belgian AIDS
      Reference Laboratories.
AB  - Eight Belgian AIDS Reference Laboratories established a multicentre quality
      control to evaluate the performance of their diagnostic human immunodeficiency
      virus type 1 (HIV-1) DNA polymerase chain reaction (PCR). A set of Belgian and
      African HIV-1 seropositive and seronegative patient samples, collected in
      Belgium, and the British Medical Research Council (MRC) HIV-1 PCR reference
      reagent kit, containing plasmid HIV-1 DNA at several dilutions in human carrier
      DNA with appropriate negative controls, were tested by the laboratories. No false
      positive results were reported. All laboratories were able to detect one to two
      copies of HIV-1 DNA. Among the 17 Belgian and African HIV-1 seropositives, some
      laboratories reported up to four indeterminate results, mainly due to failure of
      the SK38-39, SK68-69 (Ou et al. (1988) Science 239, 295-297) and/or gag881-882
      (Simmonds et al. (1990) J. Virol. 64, 864-872) primers and a poorly performing
      algorithm. Only the H1POL4235-4538 nested pol primer set, developed by one of the
      laboratories, correctly identified all the tested HIV-1 positive and negative
      samples. Consequently, the laboratories decided to evaluate these pol primers as
      a reference primer set and to standardise the testing algorithm. All laboratories
      achieved a sensitivity and specificity of 100% on testing 10 additional Belgian
      and African patient samples, when adapting a standardised algorithm based on
      three HIV-1 primer sets, one of which is the H1POL4235-4538 primer set.

PMID- 7738152
TI  - Improved potency assay of rubella vaccine: parameters for plaque formation.
AB  - Parameters for plaque formation by rubella vaccine strains licensed in Japan were
      studied. Formation of clear and large plaques on RK13 cells depends on several
      essential parameters. Plaques differed in morphology among five vaccine strains
      and the distinctiveness of the plaques was affected by pH of the agar overlay
      medium during incubation at 35 degrees C. Plaques became progressively larger in
      size as the concentration of sodium bicarbonate in the agar overlay medium
      increased from 0.04% to 0.15%, but the contrast of plaques to the background
      cells decreased markedly. The most distinct plaques of all vaccine strains were
      formed in the agar overlay medium containing 0.07% of sodium bicarbonate, i.e.,
      pH 6.83, incubated in a humidified atmosphere containing 5% CO2. The number of
      plaques formed by vaccine strains decreased at 37 degrees C. Vaccine strains
      other than MEQ11 and TCRB19 formed larger and more contrasted plaques with sharp
      outline at 35 degrees C than at 32 degrees C. MEQ11 and TCRB19 strains yielded
      higher infective virus titres at 32 degrees C, but they formed distinct plaques
      at 35 degrees C and 32 degrees C. For the plaque test, the inoculum volume was
      another critical factor for obtaining an approximate titre that reflected the
      absolute titre of the sample. A volume of 0.1 ml was feasible for a well with a
      diameter of 35 mm.

PMID- 7738153
TI  - Quantitation of human cytomegalovirus glycoprotein H gene in cells using
      competitive PCR and a rapid fluorescence-based detection system.
AB  - A technique is described for quantitation of the human cytomegalovirus (HCMV)
      glycoprotein H (gH) gene in cells using a quantitative-competitive polymerase
      chain reaction (QC-PCR). Two recombinant DNA molecules, differing in size due to
      a 92-bp deletion within the HCMV gH sequence, were used in co-amplification
      studies to construct a standard curve from which the copy number of the gH gene
      present in clinical samples could be interpolated. The use of primers labeled
      with a fluorescent dye allowed direct detection of the amplified products by
      measuring the amount of fluorescence emitted by each specific PCR fragment with
      an automated DNA sequencer coupled to a software program. This system was
      validated subsequently using bronchoalveolar lavage cells obtained from
      immunocompromised patients and found to be highly sensitive and reproducible over
      a range of 5-50,000 HCMV gH copies. This rapid procedure could easily be applied
      to study the pathogenesis of HCMV infection, identify the patients at high risk
      of developing HCMV disease, and monitor the effects of antiviral therapy at the
      molecular level.

PMID- 7738154
TI  - Validation of a screening liquid phase blocking ELISA for swine vesicular
      disease.
AB  - A direct liquid-phase blocking ELISA (LPBE) was developed for serological
      examination of swine vesicular disease (SVD). The sensitivity and specificity of
      the test were assessed on 272 and 365 sera collected on two farms where an
      outbreak had occurred. The specificity of the direct LPBE was higher than the
      specificity of the indirect LPBE. The European Community reference serum for SVD
      (RS 01-04-93), which has been adopted as the threshold for SVD serological
      examination in the European Community, had a mean titre of 2.19 in the
      neutralisation test. At a cut-off level of 2.0 in the neutralisation test, the
      sensitivity of the direct LPBE (screening at 1:432 final dilution) on the two
      farms was 90% and 99%, respectively. Based on these results, the screening
      dilution of the direct LPBE was adjusted to 1:160 final dilution, to obtain a
      sensitivity > or = 98% on both farms. Regression analyses showed a good
      correlation between the virus neutralisation test and the direct LPBE (r = 0.87).
      Compared to the indirect LPBE described before, the direct LPBE correlates better
      with the neutralisation test, has a higher specificity, and is more rapid.
      Because sera are tested in only one dilution, the test is highly suitable for the
      examination of large numbers of serum samples.

PMID- 7738155
TI  - Detection and sequence confirmation of Sin Nombre virus RNA in paraffin-embedded
      human tissues using one-step RT-PCR.
AB  - Sin Nombre virus (SNV) is the causative agent of hantavirus pulmonary syndrome
      (HPS). SNV RNA can be detected in fresh or frozen autopsy tissue samples by
      reverse transcriptase polymerase chain reaction (RT-PCR), and virus antigens can
      be identified by immunohistochemistry. A method was developed for demonstration
      of SNV RNA in formalin-fixed, paraffin-embedded tissues by RT-PCR. Virus genomes
      were detected in 8 of 12 (66.7%) fixed human tissue samples that were positive by
      immunohistochemistry, and RT-PCR prior to tissue fixation. By comparison with
      nucleotide sequences determined previously in fresh or frozen tissues of the same
      patients, identical genomic sequences were obtained, proving the authenticity of
      the PCR products. The study demonstrates that detection of SNV RNA in formalin
      fixed, paraffin-embedded archival tissue by RT-PCR is feasible. This method
      allows retrospective studies on the phylogenetic epidemiology of SNV in North
      America.

PMID- 7738156
TI  - Enhancement of feline infectious peritonitis virus type I infection in cell
      cultures using low-speed centrifugation.
AB  - The effects of centrifugation on the ability of feline infectious peritonitis
      virus (FIPV) to infect cells in culture was investigated. The infectivity titer
      was the highest when the plates were centrifuged at 400 x g (1500 rpm) for 2 h.
      All five strains classified as FIPV Type I showed infectivity titers enhanced 10
      100-fold by centrifugation at 400 x g for 2 h. The centrifugal enhancement of
      infection was obtained only by centrifugation immediately after inoculation of
      the virus, suggesting that the enhancement occurs during attachment or adsorption
      of viruses to the cells. This method may be useful for the culture of FIPV Type I
      strains.

PMID- 7738157
TI  - Creating an alternative framework for preventing rape: applying Haddon's injury
      prevention strategies.
AB  - As rape becomes recognized as a public health issue, new paradigms must be
      constructed to discover viable solutions to this highly prevalent problem.
      Although the injury prevention field has begun to examine rape and offer
      solutions, physical injuries surrounding rape tend to become the focus in injury
      prevention literature, thereby minimizing the trauma of rape itself. This article
      applies William Haddon's ten general strategies for injury prevention to rape, in
      order to shift our focus away from women and their behavior onto the systemic
      causes of rape. These strategies have the advantage of encompassing a wide
      variety of injury reduction measures from many hazards and have provided the
      means to conceptualize solutions to an extensive range of issues. The application
      of these strategies emphasizes sociocultural factors and perpetrator, not victim,
      responsibility. Through this process, a broader range of normative and structural
      changes can be identified to promote rape prevention.

PMID- 7738158
TI  - Workers, industry, and the control of information: silicosis and the Industrial
      Hygiene Foundation.
AB  - This essay focuses on the early history of industry and professional
      relationships around silicosis, the debilitating occupational lung disease,
      through a study of the role of the Industrial Health Foundation, an industry
      sponsored group which has played a critical role in shaping the nation's agenda
      regarding industrial disease. From its start during the Depression, it has
      portrayed itself as an industry-sponsored agency that depended upon detached,
      disinterested professionals and experts to develop effective programs to address
      occupational disease. As an organization that brought together professional
      industrial hygienists, business groups, government officials, academics and
      researchers it serves as a means for understanding the intertwining of industrial
      and academic agendas. We explore some of the issues that arose regarding public
      policy and scientific investigations, asking: Under what conditions is it
      appropriate for professionals and scientists to work together with industrially
      sponsored organizations? What are the pressures that shape research questions,
      the range of possible solutions, and the control of scientific data? How can
      technically trained individuals avoid real or perceived conflicts of interest? At
      what point does the ostensibly disinterested goals of professionalism conflict
      with the self-interest of the sponsoring organizations?

PMID- 7738159
TI  - A review of national television PSA campaigns for preventing alcohol-impaired
      driving, 1987-1992.
AB  - We present a content analysis of 137 public service announcements (PSAs) focused
      on alcohol-impaired driving that aired nationally on U.S. television between 1987
      and 1992. Our findings include the following: 1) Most PSAs were intended to reach
      an undifferentiated general audience, not necessarily those who are at greatest
      risk for driving after drinking. 2) Most PSAs were designed to create awareness
      of the problem of alcohol-impaired driving or to promote individual behavior
      change. 3) More PSAs were developed on the use of designated drivers than on any
      other subject. 4) About two-thirds of the PSAs included one or more celebrities
      who speak directly to the audience. Past media campaigns have tended to ignore
      the fact that people's behavior is profoundly shaped by their environment, which
      in turn is shaped by public policy. We recommend that future mass media campaigns
      against alcohol-impaired driving focus on building support for changes in
      institutional structures, public policy or law that will motivate, support, and
      sustain the efforts of individuals to alter their behavior. Television PSAs can
      play an important but somewhat limited role in support of this effort. Greater
      emphasis will need to be given instead to media advocacy strategies, including
      paid radio advertising. We further recommend that the principal organizations
      concerned about alcohol-impaired driving share their plans and develop a common
      communications strategy that will advance the public policy agenda proposed by
      the Surgeon General's Workshop on Drunk Driving.

PMID- 7738160
TI  - Legislative and regulatory mandates for mammography quality assurance.
AB  - The current practice of screening mammography in the United States has been the
      focus of numerous legislative and regulatory mandates at the state and federal
      levels, both in terms of increasing access to age-eligible women and elevating
      the quality of mammographic imaging. Several parameters have emerged as central
      to a comprehensive mammography quality assurance program: (1) equipment
      specifications, (2) equipment performance testing including radiation dose
      limits, (3) facility quality assurance procedures, and (4) personnel
      qualifications. In 1992, Congress enacted the Mammography Quality Standards Act
      (MQSA) (P.L. 102-539) to address the problem of differences in mandated standards
      across states. By October 1994, all facilities will be required to comply with
      interim MQSA regulations which were released in December 1993. However, depending
      upon the specific requirements of applicable state standards, the extent and
      nature of modifications of existing quality assurance procedures will differ for
      facilities across states as they attempt to come into compliance with uniform
      Federal standards. In addition, because some provisions within state standards
      are likely to be more stringent than Federal standards, some level of variation
      will persist. This paper reviews the components of mandated standards established
      by states and the standards established by other organizations, including the
      Federal Government, prior to the MQSA interim regulations. This review will
      provide an understanding of the highly technical and complicated requirements
      surrounding mammography quality assurance.

PMID- 7738161
TI  - A chemotactic S100 peptide enhances scavenger receptor and Mac-1 expression and
      cholesteryl ester accumulation in murine peritoneal macrophages in vivo.
AB  - In the early development of atherosclerotic plaque, monocytes are recruited to
      the arterial intima where they accumulate lipid and become foam cells. The
      recently described murine chemotactic S100 protein, CP-10, may have an important
      role in this process. Intraperitoneal injection of CP-10(42-55) (chemotactic
      hinge region peptide) into mice caused a sustained leukocyte recruitment with a
      sixfold increase in monocyte numbers over 24 h. CP-10(42-55)--elicited
      monocyte/macrophages accumulated significantly increased cholesteryl esters in
      response to acetylated LDL, both in vivo and in vitro and this was associated
      with a twofold increase in scavenger receptor expression. By contrast,
      thioglycollate- and macrophage colony-stimulating factor-elicited macrophages
      expressed levels of scavenger receptor similar to those on resident macrophages
      and did not exhibit enhanced acetylated LDL loading in vitro. The leukocyte
      integrin Mac-1 (CD11b/CD18) and its beta subunit (CD18), but neither lymphocyte
      function-associated antigen-1 nor very late activation antigen-4, were
      upregulated on monocyte/macrophages elicited by CP-10(42-55), thioglycollate, and
      macrophage colony-stimulating factor. Cholesteryl ester accumulation in vitro was
      significantly enhanced by adhesion, which appeared to involve macrophage
      activation via ligation of Mac-1. The initial events of monocyte recruitment and
      adhesion to the vessel wall may be important in macrophage foam cell development,
      and CP-10 or related S100 proteins may contribute to the early inflammatory
      events of atherogenesis by stimulating these events.

PMID- 7738163
TI  - High avidity IFN-neutralizing antibodies in pharmaceutically prepared human IgG.
AB  - This paper demonstrates and characterizes naturally occurring antibodies to
      interferon (IFN) in human IgG preparations. In vitro neutralization of the
      antiviral effect of IFN alpha and IFN beta, but not IFN gamma, was observed in 12
      of 15 normal IgG preparations. The neutralizing capacity was higher against rIFN
      alpha 2A and rIFN alpha 2C than against lymphoblastoid IFN alpha and IFN beta.
      Fruhsommer meningoencephalitis hyperimmune IgG and hepatitis-B hyperimmune IgG
      showed potent neutralization, whereas anti-rhesus D-, anti-rabies-, and anti
      tetanus IgG showed weak neutralization. Saturable binding of 125I-rIFN alpha 2A
      was demonstrated only in those IgG preparations found to neutralize the antiviral
      effect of IFN. Significant correlation between IFN binding and neutralization
      capacity was observed. The antibodies bound with Fab to rIFN alpha 2A with an
      avidity of approximately 30 pM; the majority was of the IgG1 subclass. Maximum
      binding capacity was 490 pg rIFN alpha 2A/mg IgG. Cross-binding of rIFN alpha 2C,
      lyIFN alpha N1 and IFN beta occurred with 10 and 100-200 times lower activities
      than that of rIFN alpha 2A. There was no cross-binding with rIFN gamma or rIL-6.
      IgG preparations containing anti-IFN antibodies blocked the binding of 125I-rIFN
      alpha 2A to A549 cells. In conclusion, pharmaceutically prepared human IgG
      preparations contain variable but significant levels of high-avidity IFN alpha
      and IFN beta neutralizing antibodies.

PMID- 7738162
TI  - Glucokinase and cytosolic phosphoenolpyruvate carboxykinase (GTP) in the human
      liver. Regulation of gene expression in cultured hepatocytes.
AB  - Glucokinase and phosphoenolpyruvate carboxykinase are key enzymes of glucose
      metabolism in the rat liver. The former is considered to be instrumental in
      regulating glucose hepatic release/uptake according to the glycaemia level, and
      cytosolic phosphoenolpyruvate carboxykinase is a major flux-generating enzyme for
      gluconeogenesis. The level of expression of both enzymes and the regulation of
      their mRNAs in the human liver cell were investigated. Surgical biopsies of liver
      from patients undergoing partial hepatectomies and parenchymal hepatocytes
      derived from the biopsies were used to assay glucokinase, hexokinase and
      phosphoenolpyruvate carboxykinase activities. Hepatocytes were placed in culture
      and the actions of insulin, glucagon and cAMP on glucokinase and
      phosphoenolpyruvate carboxykinase mRNAs were studied. The main results are: (a)
      glucokinase accounts for 95% of the glucose phosphorylation activity of human
      hepatocytes, although this fact is masked in assays of total liver tissue; (b)
      glucokinase activity is set at a lower level in human hepatocytes than in rat
      hepatocytes, and vice-versa for the gluconeogenic enzyme phosphoenolpyruvate
      carboxykinase; and (c) as previously shown in rat liver, glucokinase and
      phosphoenolpyruvate carboxykinase mRNAs are regulated in a reciprocal fashion in
      human hepatocytes, insulin inducing the first enzyme and repressing the latter,
      whereas glucagon has opposite effects. These data have interesting implications
      with respect to metabolic regulation and intracellular hormone signaling in the
      human liver.

PMID- 7738164
TI  - Serum low density lipoprotein of alcoholic patients is chemically modified in
      vivo and induces apolipoprotein E synthesis by macrophages.
AB  - This work was carried out to investigate the effect of alcohol drinking on serum
      LDL. Agarose gel electrophoresis showed that LDL samples from alcoholic patients
      without serious liver disease were more negatively charged and moved faster
      toward the cathode than LDL from nondrinking control subjects. Rabbit antibodies
      raised by using keyhole limpet hemocyanin modified in vitro by 4-hydroxynonenal
      or by acetaldehyde as immunogens reacted more strongly with patients' LDL than
      with control LDL, indicating the presence of oxidatively modified epitopes and
      acetaldehyde adducts in alcoholic patients' LDL. LDL of alcoholic patients has
      decreased vitamin E contents. The electromobility of LDL decreased after
      abstinence from alcohol and returned to normal in 2 wk, but this was not
      accompanied by a significant increase in its vitamin E contents. When incubated
      with mouse peritoneal macrophages, patients' LDL induced apolipoprotein E
      secretion by threefold over control LDL with a concomitant increase in cellular
      cholesterol. Our results thus demonstrate that LDL of alcoholic patients has
      lower vitamin E content, is chemically modified in vivo, and exhibits altered
      biological function. These changes in heavy alcoholic drinkers may render LDL
      more atherogenic and thereby may counter the antiatherosclerosis effects of
      moderate alcohol consumption.

PMID- 7738165
TI  - Protein S as an in vivo cofactor to activated protein C in prevention of
      microarterial thrombosis in rabbits.
AB  - The antithrombotic effects of bovine activated protein C (APC) and protein S were
      investigated in a rabbit model of microarterial thrombosis. Because of the
      species specificity of the APC-protein S interaction, bovine APC expresses potent
      anticoagulant activity in rabbit plasma only when bovine protein S is also
      present. This provided a way to assess the contribution of bovine protein S to
      the antithrombotic effect of bovine APC. Rabbits were infused with boluses of
      activated protein C (0.1, 0.2, 0.4, or 0.8 mg/kg), protein S (0.5 mg/kg), or
      activated protein C (0.1 or 0.01 mg/kg) plus protein S (0.5 mg/kg). APC alone
      produced a dose-dependent antithrombotic effect, but only the group receiving the
      highest dose differed significantly from controls. While a low dose of activated
      protein C (0.1 mg/kg) alone had no antithrombotic effect, together with protein S
      (0.5 mg/kg) it produced a potent response. The presented results demonstrate the
      in vivo significance of protein S as a cofactor to activated protein C. The data
      show that a potent antithrombotic effect, without hemorrhagic side effects or
      significant systemic anticoagulation, may be achieved by low doses of activated
      protein C when combined with protein S.

PMID- 7738166
TI  - Hepatocyte growth factor is the most potent endogenous stimulant of rabbit
      gastric epithelial cell proliferation and migration in primary culture.
AB  - Various growth factors are suggested to be involved in gastric mucosal repair.
      Our previous studies have shown that exogenous hepatocyte growth factor (HGF) has
      a proliferative effect on gastric epithelial cells. In the present study,
      comparison of the maximum proliferative effects and the optimum concentrations of
      several growth factors revealed that HGF was the most potent mitogen for gastric
      epithelial cells, as is the case for hepatocytes. Restitution of gastric
      epithelial cell monolayers was assessed using a round wound restitution model.
      HGF was the most effective agent for facilitating gastric epithelial restitution
      among those tested. A binding assay revealed specific binding of HGF to its
      receptor on gastric epithelial cells. Northern blot analysis confirmed the
      expression of specific HGF receptor mRNA (c-met) by gastric epithelial cells but
      not by gastric fibroblasts. To investigate endogenous HGF production, we
      determined the effect of gastric fibroblast-conditioned medium on epithelial
      proliferation and restitution. The conditioned medium produced similar effects to
      HGF and its activity was neutralized by an anti-HGF antibody. In addition,
      expression of HGF mRNA was detected in gastric fibroblasts but not in gastric
      epithelial cells. Our immunohistochemical study confirmed these in vitro data by
      means of demonstrating the existence and localization of HGF at human native
      gastric mucosa. HGF was localized at fibroblasts under the epithelial cell layer
      around gastric ulcers. These results suggest that HGF may be a potent endogenous
      promotor of gastric epithelial cell proliferation and migration, and may
      contribute to gastric mucosal repair through a paracrine mechanism.

PMID- 7738167
TI  - Clostridium difficile toxin B is more potent than toxin A in damaging human
      colonic epithelium in vitro.
AB  - Toxin A but not toxin B, appears to mediate intestinal damage in animal models of
      Clostridium difficile enteritis. The purpose of this study was to investigate the
      electrophysiologic and morphologic effects of purified C. difficile toxins A and
      B on human colonic mucosa in Ussing chambers. Luminal exposure of tissues to 16
      65 nM of toxin A and 0.2-29 nM of toxin B for 5 h caused dose-dependent
      epithelial damage. Potential difference, short-circuit current and resistance
      decreased by 76, 58, and 46%, respectively, with 32 nM of toxin A and by 76, 55,
      and 47%, respectively, with 3 nM of toxin B, when compared with baseline (P <
      0.05). 3 nM of toxin A did not cause electrophysiologic changes. Permeability to
      [3H]mannitol increased 16-fold after exposure to 32 nM of toxin A and to 3 nM of
      toxin B when compared with controls (P < 0.05). Light and scanning electron
      microscopy after exposure to either toxin revealed patchy damage and exfoliation
      of superficial epithelial cells, while crypt epithelium remained intact.
      Fluorescent microscopy of phalloidin-stained sections showed that both toxins
      caused disruption and condensation of cellular F-actin. Our results demonstrate
      that the human colon is approximately 10 times more sensitive to the damaging
      effects of toxin B than toxin A, suggesting that toxin B may be more important
      than toxin A in the pathogenesis of C. difficile colitis in man.

PMID- 7738168
TI  - Angiotensin II upregulates type-1 angiotensin II receptors in renal proximal
      tubule.
AB  - Angiotensin II (Ang II) is an important regulator of proximal tubule salt and
      water reabsorption. Recent studies indicate that rabbit proximal tubule
      angiotensin II receptors are the type-1 (AT1R) subtype. We studied the effect of
      Ang II on proximal tubule receptor expression. Rabbits were treated with either
      angiotensin converting enzyme inhibitors or a low salt diet to modulate
      endogenous Ang II levels. In captopril-treated rabbits, liver and glomerular AT1R
      mRNA levels increased 242 +/- 125 and 141 +/- 60%, respectively (n = 6-7; P <
      0.05), as determined by quantitative PCR. In contrast, proximal tubule AT1R mRNA
      levels decreased 40 +/- 11% (n = 6; P < 0.05). Binding of 125I Ang II to renal
      cortical basolateral membranes of captopril-treated rabbits decreased from 2.9 +/
      0.55 to 1.4 +/- 0.17 fmol/mg protein (n = 6; P < 0.025). In rabbits fed a sodium
      chloride-deficient diet for 4 wk, AT1R mRNA levels decreased 52 +/- 11% in liver
      and 43 +/- 7% in glomeruli (n = 4-5; P < 0.05), whereas they increased 141 +/-
      85% (n = 5; P < 0.05) in proximal tubule. In basolateral membranes from rabbits
      on the sodium chloride-deficient diet, specific binding of 125I Ang II increased
      from 2.1 +/- 0.2 to 4.3 +/- 1.1 fmol/mg protein (n = 7; P < 0.05). To determine
      whether Ang II directly regulates expression of proximal tubule AT1 receptors,
      further studies were performed in cultured proximal tubule cells grown from
      microdissected S1 segments of rabbit proximal tubules and immortalized by
      transfection with a replication-defective SV40 vector. Incubation of these cells
      with Ang II (10(-11) to 10(-7) M) led to concentration-dependent increases in
      both AT1R mRNA levels and specific 125I Ang II binding. Pretreatment with
      pertussis toxin inhibited Ang II stimulation of AT1R mRNA. AT1R mRNA expression
      was decreased by either forskolin or a nonhydrolyzable cAMP analogue (dibutryl
      cAMP). Simultaneous Ang II administration overcame the inhibitory effect of
      forskolin but not dibutryl cAMP. These results indicate that proximal tubule AT1R
      expression is regulated by ambient Ang II levels, and Ang II increases AT1R mRNA
      at least in part by decreasing proximal tubule cAMP generation through a
      pertussis toxin-sensitive mechanism. Upregulation of proximal tubule AT1R by Ang
      II may be important in mediating enhanced proximal tubule sodium reabsorption in
      states of elevated systemic or intrarenal Ang II.

PMID- 7738169
TI  - Growth hormone mRNA in mammary gland tumors of dogs and cats.
AB  - We have shown recently that in the dog progestin administration results in
      mammary production of immunoreactive growth hormone (GH). At present we
      demonstrate the expression of the gene encoding GH in the mammary gland of dogs
      and cats using reverse-transcriptase PCR. GH mRNA was found in the great majority
      of normal mammary tissues as well as benign and malignant mammary tumors of the
      dog and was associated with the presence of immunoreactive GH in cryostat
      sections. The mammary PCR product proved to be identical to that of the
      pituitary. The highest expression levels were found after prolonged treatment
      with progestins. In carcinomas GH mRNA was also found in progesterone receptor
      negative tissue samples, indicating that after malignant transformation GH gene
      expression may become progestin independent. GH mRNA was also present in mammary
      tissues of cats with progestin-induced fibroadenomatous changes. It is concluded
      that GH gene expression occurs in normal, hyperplastic, and neoplastic mammary
      tissue of the dog. The expression in normal tissue is stimulated by progestins
      and might mediate the progestin-stimulated development of canine mammary tumors.
      The demonstration of progestin-stimulated GH expression in mammary tissue of cats
      indicates that the phenomenon is more generalized among mammals.

PMID- 7738170
TI  - 5-Lipoxygenase is located in the euchromatin of the nucleus in resting human
      alveolar macrophages and translocates to the nuclear envelope upon cell
      activation.
AB  - 5-Lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) are two key
      proteins involved in the synthesis of leukotrienes (LT) from arachidonic acid.
      Although both alveolar macrophages (AM) and peripheral blood leukocytes (PBL)
      produce large amounts of LT after activation, 5-LO translocates from a soluble
      pool to a particulate fraction upon activation of PBL, but is contained in the
      particulate fraction in AM irrespective of activation. We have therefore examined
      the subcellular localization of 5-LO in autologous human AM and PBL collected
      from normal donors. While immunogold electron microscopy demonstrated little 5-LO
      in resting PBL, resting AM exhibited abundant 5-LO epitopes in the euchromatin
      region of the nucleus. The presence of substantial quantities of 5-LO in the
      nucleus of resting AM was verified by cell fractionation and immunoblot analysis
      and by indirect immunofluorescence microscopy. In both AM and PBL activated by
      A23187, all of the observable 5-LO immunogold labeling was found associated with
      the nuclear envelope. In resting cells of both types, FLAP was predominantly
      associated with the nuclear envelope, and its localization was not affected by
      activation with A23187. The effects of MK-886, which binds to FLAP, were examined
      in ionophore-stimulated AM and PBL. Although MK-886 inhibited LT synthesis in
      both cell types, it failed to prevent the translocation of 5-LO to the nuclear
      envelope. These results indicate that the nuclear envelope is the site at which 5
      LO interacts with FLAP and arachidonic acid to catalyze LT synthesis in activated
      AM as well as PBL, and that in resting AM the euchromatin region of the nucleus
      is the predominant source of the translocated enzyme. In addition, LT synthesis
      is a two-step process consisting of FLAP-independent translocation of 5-LO to the
      nuclear envelope followed by the FLAP-dependent activation of the enzyme.

PMID- 7738171
TI  - Monoclonality of parathyroid tumors in chronic renal failure and in primary
      parathyroid hyperplasia.
AB  - The pathogeneses of parathyroid disease in patients with uremia and nonfamilial
      primary parathyroid hyperplasia are poorly understood. Because of multigland
      involvement, it has been assumed that these common diseases predominantly involve
      polyclonal (non-neoplastic) cellular proliferations, but an overall assessment of
      their clonality has not been done. We examined the clonality of these
      hyperplastic parathyroid tumors using X-chromosome inactivation analysis with the
      M27 beta (DXS255) DNA polymorphism and by searching for monoclonal allelic losses
      at M27 beta and at loci on chromosome band 11q13. Fully 7 of 11 informative
      hemodialysis patients (64%) with uremic refractory hyperparathyroidism harbored
      at least one monoclonal parathyroid tumor (with a minimum of 12 of their 19
      available glands being monoclonal). Tumor monoclonality was demonstrable in 6 of
      16 informative patients (38%) with primary parathyroid hyperplasia.
      Histopathologic categories of nodular versus generalized hyperplasia were not
      useful predictors of clonal status. These observations indicate that monoclonal
      parathyroid neoplasms are common in patients with uremic refractory
      hyperparathyroidism and also develop in a substantial group of patients with
      sporadic primary parathyroid hyperplasia, thereby changing our concept of the
      pathogenesis of these diseases. Neoplastic transformation of preexisting
      polyclonal hyperplasia, apparently due in large part to genes not yet implicated
      in parathyroid tumorigenesis and possibly including a novel X-chromosome tumor
      suppressor gene, is likely to play a central role in these disorders.

PMID- 7738172
TI  - Altered representation of naive and memory CD8 T cell subsets in HIV-infected
      children.
AB  - CD8 T cells are divided into naive and memory subsets according to both function
      and phenotype. In HIV-negative children, the naive subset is present at high
      frequencies, whereas memory cells are virtually absent. Previous studies have
      shown that the overall number of CD8 T cells does not decrease in HIV-infected
      children. In studies here, we use multiparameter flow cytometry to distinguish
      naive from memory CD8 T cells based on expression of CD11a, CD45RA, and CD62L.
      With this methodology, we show that within the CD8 T cell population, the naive
      subset decreases markedly (HIV+ vs. HIV-, 190 vs. 370 cells/microliter; P < or =
      0.003), and that there is a reciprocal increase in memory cells, such that the
      total CD8 T cell counts remained unchanged (800 vs. 860 cells/microliter; P < or
      = 0.76). In addition, we show that for HIV-infected children, the naive CD8 T
      cell and total CD4 T cell counts correlate (chi 2 P < or = 0.001). This
      correlated loss suggests that the loss of naive CD8 T cells in HIV infection may
      contribute to the defects in cell-mediated immunity which become progressively
      worse as the HIV disease progresses and CD4 counts decrease.

PMID- 7738173
TI  - CD8 naive T cell counts decrease progressively in HIV-infected adults.
AB  - We show here that CD8 naive T cells are depleted during the asymptomatic stage of
      HIV infection. Although overall CD8 T cell numbers are increased during this
      stage, the naive CD8 T cells are progressively lost and fall in parallel with
      overall CD4 T cell counts. In addition, we show that naive CD4 T cells are
      preferentially lost as total CD4 cell counts fall. These findings, presented here
      for adults, and in the accompanying study for children, represent the first
      demonstration that HIV disease involves the loss of both CD4 T cells and CD8 T
      cells. Furthermore, they provide a new insight into the mechanisms underlying the
      immunodeficiency of HIV-infected individuals, since naive T cells are required
      for all new T cell-mediated immune responses. Studies presented here also show
      that the well-known increase in total CD8 counts in most HIV-infected individuals
      is primarily due to an expansion of memory cells. Thus, memory CD8 T cells
      comprise over 80% of the T cells in PBMC from individuals with < 200
      CD4/microliter, whereas they comprise roughly 15% in uninfected individuals.
      Since the naive and memory subsets have very different functional activities,
      this altered naive/memory T cell representation has significant consequences for
      the interpretation of data from in vitro functional studies.

PMID- 7738174
TI  - Hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression
      of HLA-A,B,C, and intercellular adhesion-1 molecules. Clues to pathogenesis of
      hepatocellular damage and response to interferon treatment in patients with
      chronic hepatitis C.
AB  - To obtain information on the mechanisms of hepatocellular damage and the
      determinants of response to interferon, hepatitis C virus (HCV) genotype, tissue
      HCV antigens, hepatocellular expression of HLA-A,B,C and intercellular adhesion-1
      molecules, and the number of lobular T lymphocytes were studied in 38 anti-HCV
      positive patients. 14 patients did not show a primary response to interferon
      treatment. HCV genotype 1b was detected in 11 of them. They displayed higher
      scores of HCV-positive hepatocytes, HLA-A,B,C, and ICAM-1 molecules expression
      than with the responders. HCV-infected hepatocytes maintained the capacity to
      express HLA-A,B,C and ICAM-1 molecules. CD8-positive T cells in contact with
      infected hepatocytes and Councilman-like bodies were observed. A significant
      correlation was found between the number of lobular CD8-positive T cells and
      alanine amino transferase levels. No differences were observed in clinical,
      biochemical, and histological features between patients with high and low number
      of hepatocytes containing HCV antigens. These data suggest a prominent role of T
      cell-mediated cytotoxicity in the genesis of hepatocellular damage. The high
      expression of interferon-inducible antigens like HLA-A,B,C molecules suggests the
      presence of strong activation of the interferon system possibly related to high
      HCV replication in nonresponder patients infected with genotype 1b.

PMID- 7738175
TI  - Two alpha subunit donor splice site mutations cause human trifunctional protein
      deficiency.
AB  - Human trifunctional protein catalyzes three steps in mitochondrial beta-oxidation
      of fatty acids, including the long chain 3-hydroxyacyl-CoA dehydrogenase step.
      Deficiency of this heterocomplex, which contains 4 alpha and 4 beta subunits,
      causes sudden unexplained infant death, a Reye-like syndrome, cardiomyopathy, or
      skeletal myopathy. We determined the molecular basis of this deficiency in a
      patient with neonatal presentation and later sudden death using reverse
      transcription and PCR amplification of his alpha subunit mRNA. We demonstrated a
      universal deletion of exon 3 (71 bp) in his mRNA. This deletion causes a
      frameshift and very early premature termination. Amplification of genomic DNA
      demonstrated that the patient was a compound heterozygote with two different
      mutations in the 5' donor splice site following exon 3: a paternally inherited G
      to A transversion at the invariant position +1 and a maternally inherited A to G
      mutation at position +3. Both allelic mutations apparently cause exon 3 skipping,
      resulting in undetectable levels of alpha subunit protein, and complete loss of
      trifunctional protein. This is the initial molecular characterization of
      trifunctional protein deficiency.

PMID- 7738176
TI  - Complete degradation of type X collagen requires the combined action of
      interstitial collagenase and osteoclast-derived cathepsin-B.
AB  - We have studied the degradation of type X collagen by metalloproteinases,
      cathepsin B, and osteoclast-derived lysates. We had previously shown (Welgus, H.
      G., C. J. Fliszar, J. L. Seltzer, T. M. Schmid, and J. J. Jeffrey. 1990. J. Biol.
      Chem. 265:13521-13527) that interstitial collagenase rapidly attacks the native
      59-kD type X molecule at two sites, rendering a final product of 32 kD. This 32
      kD fragment, however, has a Tm of 43 degrees C due to a very high amino acid
      content, and thus remains helical at physiologic core temperature. We now report
      that the 32-kD product resists any further attack by several matrix
      metalloproteinases including interstitial collagenase, 92-kD gelatinase, and
      matrilysin. However, this collagenase-generated fragment can be readily degraded
      to completion by cathepsin B at 37 degrees C and pH 4.4. Interestingly, even
      under acidic conditions, cathepsin B cannot effectively attack the whole 59-kD
      type X molecule at 37 degrees C, but only the 32-kD collagenase-generated
      fragment. Most importantly, the 32-kD fragment was also degraded at acid pH by
      cell lysates isolated from murine osteoclasts. Degradation of the 32-kD type X
      collagen fragment by osteoclast lysates exhibited the following properties: (a)
      cleavage occurred only at acidic pH (4.4) and not at neutral pH; (b) the cysteine
      proteinase inhibitors E64 and leupeptin completely blocked degradation; and (c)
      specific antibody to cathepsin B was able to inhibit much of the lysate-derived
      activity. Based upon these data, we postulate that during in vivo endochondral
      bone formation type X collagen is first degraded at neutral pH by interstitial
      collagenase secreted by resorbing cartilage-derived cells. The resulting 32-kD
      fragment is stable at core temperature and further degradation requires
      osteoclast-derived cathepsin B supplied by invading bone.

PMID- 7738177
TI  - Lipid-induced changes in intracellular iron homeostasis in vitro and in vivo.
AB  - Iron promotes cellular damage via its capacity to catalyze hydroxyl radical
      formation and by peroxidation of unsaturated lipids. The major cellular iron
      storage depot, ferritin, acts as a critical antioxidant defense by sequestering
      unbound or "free" iron, limiting its participation in damaging oxidative
      reactions. In this study, we investigated the relationship between LDL modified
      by artery wall cells and the regulation of intracellular free iron levels in the
      mouse model and in a human aortic endothelial and smooth muscle cell coculture
      system. We found in response to an atherogenic diet, fatty streak-resistant
      C3H/HeJ mice exhibited higher levels of liver apoferritin and lower intracellular
      concentrations of free iron than did fatty streak-susceptible C57 BL/6J mice.
      Also, ferritin repressor protein mRNA was not significantly suppressed after 15
      wk on the atherogenic diet in female C57BL/6J mice, which exhibit the most
      extensive fatty streak formation, but was significantly reduced in C3H/HeJ mice.
      Iron loading of coculture cells resulted in elevations of cellular free iron and
      enhanced LDL-induced monocyte transmigration. Pretreatment of cells with
      apoferritin completely abolished iron-induced LDL modification. Addition of LDL
      to cocultures resulted in elevations in lipid peroxidation products,
      intracellular free iron, apoferritin mRNA expression, and apoferritin synthesis,
      suggesting a possible relationship between the oxidative modification of LDL and
      iron metabolism.

PMID- 7738178
TI  - The expression of tumor necrosis factor in human adipose tissue. Regulation by
      obesity, weight loss, and relationship to lipoprotein lipase.
AB  - A previous study reported the increased expression of the cytokine TNF in the
      adipose tissue of genetically obese rodents. To examine this paradigm in humans,
      we studied TNF expression in lean, obese, and reduced-obese human subjects. TNF
      mRNA was demonstrated in human adipocytes and adipose tissue by Northern blotting
      and PCR. TNF protein was quantitated by Western blotting and ELISA in both
      adipose tissue and the medium surrounding adipose tissue. Using quantitative
      reverse transcriptase PCR (RT-PCR), TNF mRNA levels were examined in the adipose
      tissue of 39 nondiabetic subjects, spanning a broad range of body mass index
      (BMI). There was a significant increase in adipose TNF mRNA levels with
      increasing adiposity. There was a significant correlation between TNF mRNA and
      percent body fat (r = 0.46, P < 0.05, n = 23). TNF mRNA tended to decrease in
      very obese subjects, but when subjects with a BMI > 45 kg/m2 were excluded, there
      was a significant correlation between TNF mRNA and BMI (r = 0.37, P < 0.05, n =
      32). In addition, there was a significant decrease in adipose TNF with weight
      loss. In 11 obese subjects who lost between 14 and 66 kg (mean 34.7 kg, or 26.6%
      of initial weight), TNF mRNA levels decreased to 58% of initial levels after
      weight loss (P < 0.005), and TNF protein decreased to 46% of initial levels (P <
      0.02). TNF is known to inhibit LPL activity. When fasting adipose LPL activity
      was measured in these subjects, there was a significant inverse relationship
      between TNF expression and LPL activity (r = -0.39, P < 0.02, n = 39). With
      weight loss, LPL activity increased to 411% of initial levels. However, the
      magnitude of the increase in LPL did not correlate with the decrease in TNF.
      Thus, TNF is expressed in human adipocytes. TNF is elevated in most obese
      subjects and is decreased by weight loss. In addition, there is an inverse
      relationship between TNF and LPL expression. These data suggest that endogenous
      TNF expression in adipose tissue may help limit obesity in some subjects, perhaps
      by increasing insulin resistance and decreasing LPL.

PMID- 7738179
TI  - Correlation between disease phenotype and genetic heterogeneity in rheumatoid
      arthritis.
AB  - RA is a heterogeneous group of disorders characterized by variations in clinical
      manifestations, disease course, and probably response to therapeutic
      interventions. We have addressed the question whether genetically and potentially
      etiologically more homogeneous subgroups of RA patients can be defined based upon
      the expression of the RA-linked sequence motif in the third hypervariable region
      of the HLA-DRB1 gene. Genetic comparison of patients classified upon clinical
      manifestation and disease course demonstrated that patients with mild disease
      were genetically distinct from those progressing to severe and destructive
      disease. Specifically, rheumatoid factor (RF) negative patients preferentially
      expressed RA-linked HLA-DRB1 alleles with an arginine substitution in position
      71, whereas the alleles with a lysine substitution in position 71 accumulated in
      RF+ patients. RF- patients were further subdivided based on clinical markers
      (time of onset of erosive disease and requirement for aggressive therapy).
      Clinical heterogeneity correlated with genetic heterogeneity. Patients with early
      erosive disease and patients requiring aggressive therapy frequently typed HLA
      DRB1*04+. Patients with late erosive/nonerosive disease or a benign disease
      course manageable with nonaggressive treatment preferentially expressed HLA
      DRB1*01 or lacked an RA-linked haplotype. These data indicate that the
      heterogeneity of RA reflects genetic differences. Sequence variations within the
      disease-linked sequence motif, as well as polymorphisms surrounding the candidate
      genetic element, affect pattern, course, and treatment response of RA. Amino acid
      position 71 in the HLA-DRB1 gene has a unique role, the understanding of which
      may provide important clues to disease etiology.

PMID- 7738180
TI  - Comparison of alendronate and sodium fluoride effects on cancellous and cortical
      bone in minipigs. A one-year study.
AB  - Fluoride stimulates trabecular bone formation, whereas bisphosphonates reduce
      bone resorption and turnover. Fracture prevention has not been convincingly
      demonstrated for either treatment so far. We compared the effects of 1-yr
      treatment of 9-mo-old minipigs with sodium fluoride (NaF, 2 mg/kg/d p.o.) or
      alendronate (ALN, 4 amino-1-hydroxybutylidene bisphosphonate monosodium, 1
      mg/kg/d p.o.) on the biomechanical and histomorphometric properties of pig bones.
      As expected, NaF increased and ALN decreased bone turnover, but in these normal
      animals neither changed mean bone volume. NaF reduced the strength of cancellous
      bone from the L4 vertebra, relative to control animals, and the stiffness
      (resistance to deformation) of the femora, relative to the ALN group. In the ALN
      treated animals, there was a strong positive correlation between bone strength
      and L5 cancellous bone volume, but no such correlation was observed in the NaF
      group. Furthermore, the modulus (resistance to deformation of the tissue) was
      inversely related to NaF content and there was a relative decrease in bone
      strength above 0.25 mg NaF/g bone. Moreover, within the range of changes measured
      in this study, there was an inverse correlation between bone turnover, estimated
      as the percentage of osteoid surface, and modulus. These findings have relevant
      implications regarding the use of these agents for osteoporosis therapy.

PMID- 7738182
TI  - Characterization of a protein cofactor that mediates protein kinase A regulation
      of the renal brush border membrane Na(+)-H+ exchanger.
AB  - Activation of cAMP-dependent protein kinase A inhibits the renal proximal tubule
      brush border membrane Na(+)-H+ exchanger by a process involving participation of
      a regulatory cofactor (NHE-RF) that is distinct from the transporter itself.
      Recent studies from this laboratory reported a partial amino acid sequence of
      this putative cofactor (Weinman, E. J., D. H. Steplock, and S. Shenolikar. 1993.
      J. Clin. Invest. 92:1781-1786). The present experiments detail the structure of
      the NHE-RF protein as determined from molecular cloning studies. A codon-biased
      oligonucleotide probe to a portion of the amino acid sequence of the putative
      cofactor was used to isolate a 1.9-kb cDNA from a rabbit renal library. The
      encoded protein is 358 amino acids in length and is rich in proline residues.
      Search of existing data bases indicates that NHE-RF is a unique protein. Using a
      reticulocyte lysate, the cDNA translated a product of approximately 44 kD, which
      was recognized by an affinity-purified polyclonal antibody to NHE-RF. Potential
      phosphorylation sites for protein kinase A are present. The mRNA for the protein
      is expressed in kidney, proximal small intestine, and liver. Reverse
      transcription/PCR studies in the kidney indicate the presence of mRNA for NHE-RF
      in several distinct nephron segments including the proximal tubule.

PMID- 7738181
TI  - Relation of myocardial oxygen consumption and function to high energy phosphate
      utilization during graded hypoxia and reoxygenation in sheep in vivo.
AB  - This study investigates the relation between myocardial oxygen consumption
      (MVO2), function, and high energy phosphates during severe hypoxia and
      reoxygenation in sheep in vivo. Graded hypoxia was performed in open-chested
      sheep to adjust PO2 to values where rapid depletion of energy stores occurred.
      Highly time-resolved 31P nuclear magnetic resonance spectroscopy enabled
      monitoring of myocardial phosphates throughout hypoxia and recovery with
      simultaneous MVO2 measurement. Sheep undergoing graded hypoxia (n = 5) with an
      arterial PO2 nadir of 13.4 +/- 0.5 mmHg, demonstrated maintained rates of oxygen
      consumption with large changes in coronary flow as phosphocreatine (PCr)
      decreased within 4 min to 40 +/- 7% of baseline. ATP utilization rate increased
      simultaneously 59 +/- 20%. Recovery was accompanied by marked increases in MVO2
      from 2.0 +/- 0.5 to 7.2 +/- 1.9 mumol/g per min, while PCr recovery rate was 4.3
      +/- 0.6 mumol/g per min. ATP decreased to 75 +/- 6% of baseline during severe
      hypoxia and did not recover. Sheep (n = 5) which underwent moderate hypoxia (PO2
      maintained 25-35 mmHg for 10 min) did not demonstrate change in PCr or ATP.
      Functional and work assessment (n = 4) revealed that cardiac power increased
      during the graded hypoxia and was maintained through early reoxygenation. These
      studies show that (a) MVO2 does not decrease during oxygen deprivation in vivo
      despite marked and rapid decreases in high energy phosphates; (b) contractile
      function during hypoxia in vivo does not decrease during periods of PCr depletion
      and intracellular phosphate accumulation, and this may be related to marked
      increases in circulating catecholamines during global hypoxia. The measured
      creatine rephosphorylation rate is 34 +/- 11% of predicted (P < 0.01) calculated
      from reoxygenation parameters, which indicates that some mitochondrial
      respiratory uncoupling also occurs during the rephosphorylation period.

PMID- 7738184
TI  - Impaired activation of adipocyte lipolysis in familial combined hyperlipidemia.
AB  - The pathophysiology of familial combined hyperlipidemia (FCHL) is unknown, but
      altered lipid turnover in peripheral tissues as well as hepatic overproduction of
      apolipoprotein B have been suggested as possible causes. In the present study, we
      explored whether a change in triglyceride breakdown by lipolysis in fat cells is
      present in FCHL. Lipolysis activation by catecholamines was examined in isolated
      subcutaneous adipocytes from 10 patients with FCHL and 22 healthy control
      subjects. Lipolysis rate was linear for at least 3 h in both groups. However, a
      marked (approximately 65%) decrease in the lipolytic response to noradrenaline
      was found in FCHL. This was also true when lipolysis was maximally stimulated at
      the receptor level with isoprenaline (nonselective beta-adrenergic agonist), at
      the adenylyl cyclase level with forskolin, or at the level of the protein kinase
      hormone-sensitive lipase complex with dibutyryl cAMP. The maximum enzymatic
      activity of hormone-sensitive lipase was decreased by approximately 40% in FCHL.
      On the other hand, the lipolytic sensitivity of alpha 2-, beta 1-, and beta 2
      adrenoceptors was normal in this condition, as was the number and affinity of
      beta 1- and beta 2-adrenoceptors. Variations in the maximum lipolysis rate
      correlated significantly with the variations in hormone-sensitive lipase activity
      in the whole material, and with the serum values for triglycerides, HDL
      cholesterol and apoB lipoprotein within the control group, but the serum
      triglyceride values in FCHL were higher than this correlation predicted. In
      conclusion, the data demonstrate a marked resistance to the lipolytic effect of
      catecholamines in fat cells from patients with FCHL, in spite of normal
      adrenoceptor function. The lipolytic defect appears predominantly to be due to a
      defect in hormone-sensitive lipase, and may be of importance in the
      pathophysiology of FCHL.

PMID- 7738183
TI  - The rabbit pulmonary cytochrome P450 arachidonic acid metabolic pathway:
      characterization and significance.
AB  - Cytochrome P450 metabolizes arachidonic acid to several unique and biologically
      active compounds in rabbit liver and kidney. Microsomal fractions prepared from
      rabbit lung homogenates metabolized arachidonic acid through cytochrome P450
      pathways, yielding cis-epoxyeicosatrienoic acids (EETs) and their hydration
      products, vic-dihydroxyeicosatrienoic acids, mid-chain cis-trans conjugated
      dienols, and 19- and 20-hydroxyeicosatetraenoic acids. Inhibition studies using
      polyclonal antibodies prepared against purified CYP2B4 demonstrated 100%
      inhibition of arachidonic acid epoxide formation. Purified CYP2B4, reconstituted
      in the presence of NADPH-cytochrome P450 reductase and cytochrome b5, metabolized
      arachidonic acid, producing primarily EETs. EETs were detected in lung homogenate
      using gas chromatography/mass spectroscopy, providing evidence for the in vivo
      pulmonary cytochrome P450 epoxidation of arachidonic acid. Chiral analysis of
      these lung EETs demonstrated a preference for the 14(R),15(S)-, 11(S),12(R)-, and
      8(S),9(R)-EET enantiomers. Both EETs and vic-dihydroxyeicosatrienoic acids were
      detected in bronchoalveolar lavage fluid. At micromolar concentrations,
      methylated 5,6-EET and 8,9-EET significantly relaxed histamine-contracted guinea
      pig hilar bronchi in vitro. In contrast, 20-hydroxyeicosatetraenoic acid caused
      contraction to near maximal tension. We conclude that CYP2B4, an abundant rabbit
      lung cytochrome P450 enzyme, is the primary constitutive pulmonary arachidonic
      acid epoxygenase and that these locally produced, biologically active eicosanoids
      may be involved in maintaining homeostasis within the lung.

PMID- 7738185
TI  - Mechanism of intestinal absorption. Effect of clonidine on rabbit ileal villus
      and crypt cells.
AB  - In intact tissue studies, intestinal absorptogogues stimulate NaCl absorption
      that occurs via the dual operation of Na:H and Cl:HCO3 exchanges on the brush
      border membrane (BBM) of villus cells. To determine the cellular mechanism of
      action of an intestinal absorptogogue, the effect of clonidine was determined on
      Na:H and Cl:HCO3 exchange in rabbit ileal villus and crypt cells. Using 2,7
      bis(carboxyethyl)-5,6-carboxy-fluorescein we have previously shown that recovery
      from an acid load occurs via Na:H exchange, whereas recovery from an alkaline
      load occurs via Cl:HCO3 exchange in both cells. In villus cells, the rate of
      recovery from a propionate-induced alkaline load was not altered by clonidine.
      However, clonidine stimulated recovery from an acid load induced by NH4Cl, Na
      removal, or amiloride. These data suggest that clonidine stimulates Na:H exchange
      in villus cells. In crypt cells, the rate of recovery from a propionate-induced
      alkaline load was also not altered by clonidine. However, in crypt cells, unlike
      the villus cells, clonidine inhibited recovery from an acid load induced by
      NH4Cl, Na removal, or amiloride. These data suggest that clonidine inhibits Na:H
      exchange in crypt cells. Stimulation of Na:H exchange on the BBM of villus cells
      would be expected to stimulate coupled NaCl absorption (which occurs by coupling
      of Na:H and Cl:HCO3 exchange). Inhibition of Na:H in crypt cells, known to be
      present only on the basolateral membrane, will acidify the cell and may inhibit
      Cl:HCO3 exchange on the BBM, resulting in the inhibition of HCO3 secretion.

PMID- 7738186
TI  - Generation of a drug resistance profile by quantitation of mdr-1/P-glycoprotein
      in the cell lines of the National Cancer Institute Anticancer Drug Screen.
AB  - Identifying new chemotherapeutic agents and characterizing mechanisms of
      resistance may improve cancer treatment. The Anticancer Drug Screen of the
      National Cancer Institute uses 60 cell lines to identify new agents. Expression
      of mdr-1/P-glycoprotein was measured by quantitative PCR. Expression was detected
      in 39 cell lines; the highest levels were in renal and colon carcinomas.
      Expression was also detected in all melanomas and central nervous system tumors,
      but in only one ovarian carcinoma and one leukemia cell line. Using a modified
      version of the COMPARE program, a high correlation was found between expression
      of mdr-1 and cellular resistance to a large number of compounds. Evidence that
      these compounds are P-glycoprotein substrates includes: (a) enhancement of
      cytotoxicity by verapamil; (b) demonstration of cross-resistance in a multidrug
      resistant cell line, (c) ability to antagonize P-glycoprotein, increasing
      vinblastine accumulation by decreasing efflux; and (d) inhibition of
      photoaffinity labeling by azidopine. Identification of many heretofore
      unrecognized compounds as substrates indicates that P-glycoprotein has a broader
      substrate specificity than previously recognized. This study confirms the
      validity of this novel approach and provides the basis for similar studies
      examining a diverse group of gene products, including other resistance
      mechanisms, putative drug targets, and genes involved in the cell cycle and
      apoptosis.

PMID- 7738187
TI  - 1,25-Dihydroxyvitamin D3 and 12-O-tetradecanoyl phorbol 13-acetate cause
      differential activation of Ca(2+)-dependent and Ca(2+)-independent isoforms of
      protein kinase C in rat colonocytes.
AB  - Considerable evidence that alterations in protein kinase C (PKC) are intimately
      involved in important physiologic and pathologic processes in many cells,
      including colonic epithelial cells, has accumulated. In this regard, phorbol
      esters, a class of potent PKC activators, have been found to induce a number of
      cellular events in normal or transformed colonocytes. In addition, our laboratory
      has demonstrated that the major active metabolite of vitamin D3, 1,25(OH)2D3,
      also rapidly (seconds-minutes) activated PKC and increased intracellular calcium
      in isolated rat colonocytes. These acute responses, however, were lost in vitamin
      D deficiency and partially restored with the in vivo repletion of 1,25(OH)2D3.
      The Ca(2+)-independent or novel isoforms of PKC expressed in the rat colon and
      the isoform-specific responses of PKC to acute treatment with phorbol esters or
      1,25(OH)2D3 have not been previously characterized. Moreover, the effects of
      vitamin D status on PKC isoform expression, distribution, and response to
      agonists are also unknown. In the present experiments, in addition to PKC-alpha,
      rat colonocytes were found to express the novel isoforms delta, epsilon, and zeta
      by Western blotting using isoform-specific PKC antibodies. The tumor-promoting
      phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate, caused time- and
      concentration-dependent translocations of all these isoforms except PKC-zeta. In
      vitamin D deficiency, there were no alterations in colonic PKC isoform expression
      but significant changes in the subcellular distribution of PKC-alpha, -delta, and
      -zeta. Acute treatment of colonocytes from D-sufficient, but not D-deficient,
      rats with 1,25(OH)2D3 caused a rapid transient redistribution of only PKC-alpha
      from the soluble to the particulate fraction. The alterations in PKC isoform
      distribution and PKC-alpha responsiveness to 1,25(OH)2D3 in vitamin D deficiency
      were partially, but significantly, restored with 5-7 d in vivo repletion of this
      secosteroid. Both 12-O-tetradecanoyl phorbol 13-acetate and 1,25(OH)2D3 activated
      endogenous PKC, as assessed by inhibition of myristoylated alanine-rich C kinase
      substrate back-phosphorylation by exogenous PKC. These studies indicate that PKC
      alpha, -delta, and/or -epsilon likely mediate important phorbol ester-stimulated
      events described in the rat colon. In contrast, PKC-alpha is implicated in the
      rapid (s-min) PKC-dependent events initiated by 1,25(OH)2D3 in rat colonocytes.

PMID- 7738188
TI  - A noninvasive method to measure splanchnic glucose uptake after oral glucose
      administration.
AB  - We have developed a noninvasive method to estimate splanchnic glucose uptake
      (SGU) in humans (oral glucose clamp technique [OG-CLAMP]), which combines a
      hyperinsulinemic clamp with an oral glucose load (oral glucose tolerance test).
      We validated this method in 12 nondiabetic subjects using hepatic vein
      catheterization (HVC) during an oral glucose tolerance test. During HVC,
      splanchnic blood flow increased from 1,395 +/- 64 to 1,935 +/- 109 ml/min,
      returning to basal after 180 min and accounted for 45 +/- 7% of SGU in lean and
      19 +/- 5% in obese subjects (P < 0.05). SGU estimated during the OG-CLAMP was 22
      +/- 2% of the glucose load, and this was significantly correlated (r = 0.90, P <
      0.0001) with SGU (35 +/- 4%) and with first pass SGU (24 +/- 3%; r = 0.83, P <
      0.001) measured during HVC. SGU was higher in obese than in lean subjects during
      OG-CLAMP (27 +/- 1% vs 18 +/- 3%, P < 0.01) and HVC (44 +/- 4% vs 26 +/- 5%, P <
      0.05). In conclusion, SGU during the OG-CLAMP is well correlated to SGU measured
      during HVC. An increase in splanchnic blood flow is a major contributor to SGU in
      lean subjects. SGU is increased in obese subjects as measured by both methods.

PMID- 7738189
TI  - Demonstration of an in vivo functional beta 3-adrenoceptor in man.
AB  - Although it is well established in several mammalian species that beta 3
      adrenoceptors play a major role in regulating lipolysis and thermogenesis in
      adipose tissue, the functional existence and role of this receptor subtype in man
      has been controversial. We investigated whether the beta 3-adrenoceptor
      functionally co-exists with beta 1- and beta 2-adrenoceptors in vivo in human
      adipose tissue. Subcutaneous abdominal adipose tissue of healthy non-obese
      subjects was microdialyzed with equimolar concentrations of dobutamine (selective
      beta 1-adrenoceptor agonist), terbutaline (selective beta 2-adrenoceptor
      agonist), or CGP 12177 (selective beta 3-adrenoceptor agonist). All three agents
      caused a rapid, sustained, concentration-dependent and significant elevation of
      the glycerol level in the microdialysate (lipolysis index). However, only
      terbutaline stimulated the nutritive blood flow in adipose tissue, as measured by
      an ethanol escape technique. Dobutamine and CGP 12177 was equally effective in
      elevating the glycerol level (maximum effect 150% above baseline). Terbutaline
      was significantly more effective than the other two beta-agonists (maximum effect
      200% above baseline). When adipose tissue was pretreated with the beta 1/beta 2
      selective adrenoceptor blocker propranolol the glycerol increasing effect of
      dobutamine or terbutaline was inhibited by 80-85% but the glycerol response to
      CGP 12177 was not influenced. It is concluded that a functional beta 3
      adrenoceptor is present in vivo in man. It co-exists with beta 1- and beta 2
      adrenoceptors in adipose tissue and may therefore play a role in lipolysis
      regulation. It appears, however, that the beta 2-adrenoceptor is the most
      important beta-adrenoceptor subtype for the mobilization of lipids from abdominal
      subcutaneous adipose tissue because of its concomitant stimulatory effect on
      lipolysis and blood flow.

PMID- 7738190
TI  - Transgenic mice expressing high levels of human apolipoprotein B develop severe
      atherosclerotic lesions in response to a high-fat diet.
AB  - We previously generated transgenic mice expressing human apolipoprotein (apo-) B
      and demonstrated that the plasma of chow-fed transgenic animals contained
      markedly increased amounts of LDL (Linton, M. F., R. V. Farese, Jr., G. Chiesa,
      D. S. Grass, P. Chin, R. E. Hammer, H. H. Hobbs, and S. G. Young 1992. J. Clin.
      Invest. 92:3029-3037). In this study, we fed groups of transgenic and
      nontransgenic mice either a chow diet or a diet high in fat (16%) and cholesterol
      (1.25%). Lipid and lipoprotein levels were assessed, and after 18 wk of diet, the
      extent of aortic atherosclerotic lesions in each group of animals was quantified.
      Compared with the female transgenic mice on the chow diet, female transgenic mice
      on the high-fat diet had higher plasma levels of cholesterol (312 +/- 17 vs 144
      +/- 7 mg/dl; P < 0.0001) and human apo-B (120 +/- 8 vs 84 +/- 3 mg/dl; P <
      0.0001). The higher human apo-B levels were due to increased plasma levels of
      human apo-B48; the human apo-B100 levels did not differ in animals on the two
      diets. In mice on the high-fat diet, most of the human apo-B48 and apo-B100 was
      found in LDL-sized particles. Compared with nontransgenic mice on the high-fat
      diet, the transgenic animals on the high-fat diet had significantly increased
      levels of total cholesterol (312 +/- 17 vs 230 +/- 19 mg/dl; P < 0.0001) and non
      HDL cholesterol (283 +/- 17 vs 193 +/- 19 mg/dl; P < 0.0001). The extent of
      atherosclerotic lesion development within the ascending aorta was quantified by
      measuring total lesion area in 60 progressive sections, using computer-assisted
      image analysis. Neither the chow-fed transgenic mice nor the chow-fed
      nontransgenic mice had significant atherosclerotic lesions. Nontransgenic animals
      on the high-fat diet had relatively small atherosclerotic lesions (< 15,000
      microns 2/section), almost all of which were confined to the proximal 400 microns
      of the aorta near the aortic valve. In contrast, transgenic animals on the high
      fat diet had extensive atherosclerotic lesions (> 160,000 microns 2/section) that
      were widely distributed throughout the proximal 1,200 microns of the aorta. Thus,
      human apo-B expression, in the setting of a diet rich in fats, causes severe
      atherosclerosis in mice.

PMID- 7738191
TI  - Apoptosis of human vascular smooth muscle cells derived from normal vessels and
      coronary atherosclerotic plaques.
AB  - We studied death of human vascular smooth muscle cells derived from coronary
      plaques and normal coronary arteries and aorta. Cells from normal arteries
      underwent death only upon removal of serum growth factors. In contrast, plaque
      derived cells died even in high serum conditions, and death increased after serum
      withdrawal. Death was characteristically by apoptosis in both normal and plaque
      derived cells, as determined by time-lapse videomicroscopy, electron microscopy,
      and DNA fragmentation patterns. IGF-1 and PDGF were identified as potent survival
      factors in serum, whereas EGF and basic fibroblast growth factor had little
      effect. Stable expression of bcl-2, a protooncogene that regulates apoptosis in
      other cell lines, protected smooth muscle cells from apoptosis, although there
      was no detectable difference in endogenous bcl-2 expression between cells from
      plaques or normal vessels. We conclude that apoptosis of human vascular smooth
      muscle cells is regulated by both specific gene products and local cytokines
      acting as survival factors. Apoptosis may therefore regulate cell mass in the
      normal arterial wall and the higher rates of apoptosis seen in plaque smooth
      muscle cells may ultimately contribute to plaque rupture and breakdown and thus
      to the clinical sequelae of atherosclerosis.

PMID- 7738192
TI  - Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes
      from the cell cycle in human and rat hearts.
AB  - The regulated expression of cyclins controls the cell cycle. Because
      cardiomyocytes in adult mammals withdraw permanently from the cell cycle and thus
      cannot regenerate after injury, we examined cyclin expression during development
      by comparing cyclin A-E mRNA levels in fetal and adult human hearts. Cyclin B
      mRNA was detectable in adult hearts, although at a level markedly lower than that
      in fetal hearts. Levels of cyclin C, D1, D2, D3, and E mRNA were essentially
      identical in the two groups. In contrast, cyclin A mRNA was undetectable in adult
      hearts whereas cyclin A mRNA and protein were readily detectable in fetal hearts
      and cardiomyocytes, respectively. We then measured cyclin A mRNA and protein
      levels in rat hearts at four stages of development (fetal and 2, 14, and 28 d).
      Cyclin A mRNA and protein levels decreased quickly after birth (to 37% at day 2)
      and became undetectable within 14 d, an observation consistent with reports that
      cardiomyocytes stop replicating in rats by the second to third postnatal week.
      This disappearance of cyclin A gene expression in human and rat hearts at the
      time cardiomyocytes become terminally differentiated suggests that cyclin A
      downregulation is important in the permanent withdrawal of cardiomyocytes from
      the cell cycle.

PMID- 7738193
TI  - The aged epidermal permeability barrier. Structural, functional, and lipid
      biochemical abnormalities in humans and a senescent murine model.
AB  - Aged epidermis displays altered drug permeability, increased susceptibility to
      irritant contact dermatitis, and often severe xerosis, suggesting compromise of
      the aged epidermal barrier. To delineate the functional, structural, and lipid
      biochemical basis of epidermal aging, we compared barrier function in young (20
      30 yr) vs aged (> 80 yr) human subjects, and in a murine model. Baseline
      transepidermal water loss in both aged humans and senescent mice was subnormal.
      However, the aged barrier was perturbed more readily with either acetone or tape
      stripping (18 +/- 2 strippings vs 31 +/- 5 strippings in aged vs young human
      subjects, respectively). Moreover, after either acetone treatment or tape
      stripping, the barrier recovered more slowly in aged than in young human subjects
      (50 and 80% recovery at 24 and 72 h, respectively, in young subjects vs 15%
      recovery at 24 h in aged subjects), followed by a further delay over the next 6
      d. Similar differences in barrier recovery were seen in senescent vs young mice.
      Although the total lipid content was decreased in the stratum corneum of aged
      mice (approximately 30%), the distribution of ceramides (including ceramide 1),
      cholesterol, and free fatty acids was unchanged. Moreover, a normal complement of
      esterified, very long-chain fatty acids was present. Finally, stratum corneum
      lamellar bilayers displayed normal substructure and dimensions, but were focally
      decreased in number, with decreased secretion of lamellar body contents. Thus,
      assessment of barrier function in aged epidermis under basal conditions is
      misleading, since both barrier integrity and barrier repair are markedly
      abnormal. These functional changes can be attributed to a global deficiency in
      all key stratum corneum lipids, resulting in decreased lamellar bilayers in the
      stratum corneum interstices. This constellation of findings may explain the
      increased susceptibility of intrinsically aged skin to exogenous and
      environmental insults.

PMID- 7738194
TI  - A synthetic tumor necrosis factor-alpha agonist peptide enhances human
      polymorphonuclear leukocyte-mediated killing of Plasmodium falciparum in vitro
      and suppresses Plasmodium chabaudi infection in mice.
AB  - A peptide corresponding to residues 70-80 of the TNF-alpha polypeptide was
      synthesized and shown to enhance human PMN-mediated killing of Plasmodium
      falciparum in vitro and reduced the Plasmodium chabaudi parasitemia in mice.
      Studies of the mechanism of action showed that the peptide, TNF(70-80),
      stimulated and primed PMN for an increased respiratory burst and release of
      granule constituents in response to a second agonist. The PMN-stimulatory
      activity of the peptide was inhibited by mAbs against the p55 and p75 TNF
      receptors and a TNF-neutralizing mAb. Analysis of PMN receptor expression showed
      that CR3 (CD18/CD11b) and Fc gamma RIII were upregulated by TNF(70-80), which was
      consistent with the peptide's ability to enhance parasite killing by PMN. The
      peptide, unlike TNF, did not increase the expression of adhesion molecules on
      endothelial cells and failed to promote binding of P. falciparum-infected
      erythrocytes to endothelial cells. TNF(70-80) also inhibited the TNF-induced
      increase in adhesion of P. falciparum-infected erythrocytes to endothelial cells.
      The results demonstrate that the host-protective effects of TNF can be retained
      while toxic effects are eliminated using a selected, characterized subunit of the
      cytokine.

PMID- 7738195
TI  - Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication by
      transcriptional activation at the long terminal repeat.
AB  - Tuberculosis has emerged as an epidemic fueled by the large number of individuals
      infected with the human immunodeficiency virus, especially those who are
      injecting drug users. We found a striking increase from 4- to 208-fold in p24
      levels in bronchoalveolar lavage fluid from involved sites of Mycobacterium
      tuberculosis infection vs uninvolved sites in three HIV+ patients. We used an in
      vitro cell culture model to determine if tuberculosis could activate replication
      of HIV-1. Mononuclear phagocyte cell lines U937 and THP-1 infected with HIV-1JR
      CSF, in vitro and stimulated with live M. tuberculosis H37Ra, had a threefold
      increase in p24 in culture supernatants. Using the HIV-1 long terminal repeat
      with a chloramphenicol acetyltransferase (CAT) reporter construct, live M.
      tuberculosis increased transcription 20-fold in THP-1 cells, and cell wall
      components stimulated CAT expression to a lesser extent. The nuclear factor-kappa
      B enhancer element was responsible for the majority of the increased CAT activity
      although two upstream nuclear factor-IL6 sites may also contribute to enhanced
      transcription. Antibodies to TNF-alpha and IL-1 inhibited the increase in CAT
      activity of the HIV-1 long terminal repeat by M. tuberculosis from 21-fold to 8
      fold. Stimulation of HIV-1 replication by M. tuberculosis may exacerbate
      dysfunction of the host immune response in dually infected individuals.

PMID- 7738196
TI  - Vertebral size in elderly women with osteoporosis. Mechanical implications and
      relationship to fractures.
AB  - Reductions in bone density are a major determinant of vertebral fractures in the
      elderly population. However, women have a greater incidence of fractures than
      men, although their spinal bone densities are comparable. Recent observations
      indicate that women have 20-25% smaller vertebrae than men after accounting for
      differences in body size. To assess whether elderly women with vertebral
      fractures have smaller vertebrae than women who do not experience fractures, we
      reviewed 1,061 computed tomography bone density studies and gathered 32-matched
      pairs of elderly women, with reduced bone density, whose main difference was
      absence or presence of vertebral fractures. Detailed measurements of the
      dimensions of unfractured vertebrae and the moment arm of spinal musculature from
      T12 to L4 were calculated from computed tomography images in the 32 pairs of
      women matched for race, age, height, weight, and bone density. The cross
      sectional area of unfractured vertebrae was 4.9-11.5% (10.5 +/- 1.4 vs 9.7 +/-
      1.5 cm2; P < 0.0001) smaller and the moment arm of spinal musculature was 3.2
      7.4% (56.4 +/- 5.1 vs 53.1 +/- 4.4 mm; P < 0.0001) shorter in women with
      fractures, implying that mechanical stress within intact vertebral bodies for
      equivalent loads is 5-17% greater in women with fractures compared to women
      without fractures. Such significant variations are very likely to contribute to
      vertebral fractures in osteoporotic women.

PMID- 7738197
TI  - Prevention of diabetic nephropathy in db/db mice with glycated albumin
      antagonists. A novel treatment strategy.
AB  - Accelerated protein glycation in diabetes has been mechanistically linked to the
      pathogenesis of diabetic nephropathy. Because glycated albumin induces
      abnormalities in cultured mesangial cells that resemble those characterizing the
      glomerular mesangium in diabetes, and monoclonal antibodies (A717) specific for
      Amadori-modified glycated albumin prevent these abnormalities, we postulated that
      in vivo administration of A717 could retard the progression of diabetic
      nephropathy. To test this hypothesis, diabetic db/db mice and their nondiabetic
      db/m littermates were treated with eight consecutive weekly injections of 150
      micrograms of A717 (Fab fragments) to reduce the elevated plasma glycated albumin
      concentration, or with irrelevant murine IgG (MIg). Relative to nondiabetics,
      diabetic mice (MIg treated) manifested proteinuria (3.35 +/- 0.15 vs 0.87 +/- 0.1
      mg albumin/mg creatinine), 3.8-fold increase in mesangial matrix fraction, and
      renal cortical overexpression of mRNAs encoding alpha 1(IV) collagen (2.6-fold
      increase) and fibronectin (3.8-fold increase). Treatment of db/db mice with A717
      significantly reduced the proteinuria (1.52 +/- 0.3 mg/mg creatinine), inhibited
      mesangial matrix expansion, and attenuated overexpression of matrix mRNAs. The
      nephropathic protective effects of A717 were independent of any change in blood
      glucose concentrations. Antibodies unreactive with glycated albumin did not
      duplicate the beneficial effects of A717. Thus, abrogating the biologic effects
      of increased glycated albumin with A717 has a salutary influence on the
      pathogenesis of diabetic nephropathy and has novel therapeutic potential in its
      management.

PMID- 7738198
TI  - Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in
      normal adult hematopoiesis.
AB  - We have explored the expression of the transcription factors GATA-1, GATA-2, and
      NF-E2 in purified early hematopoietic progenitor cells (HPCs) induced to gradual
      unilineage erythroid or granulocytic differentiation by growth factor stimulus.
      GATA-2 mRNA and protein, already expressed in quiescent HPCs, is rapidly induced
      as early as 3 h after growth factor stimulus, but then declines in advanced
      erythroid and granulocytic differentiation and maturation. NF-E2 and GATA-1 mRNAs
      and proteins, though not detected in quiescent HPCs, are gradually induced at 24
      48 h in both erythroid and granulocytic culture. Beginning at late
      differentiation/early maturation stage, both transcription factors are further
      accumulated in the erythroid pathway, whereas they are suppressed in the
      granulopoietic series. Similarly, the erythropoietin receptor (EpR) is induced
      and sustainedly expressed during erythroid differentiation, although beginning at
      later times (i.e., day 5), whereas it is barely expressed in the granulopoietic
      pathway. In the first series of functional studies, HPCs were treated with
      antisense oligomers targeted to transcription factor mRNA: inhibition of GATA-2
      expression caused a decreased number of both erythroid and granulocyte-monocytic
      clones, whereas inhibition of NF-E2 or GATA-1 expression induced a selective
      impairment of erythroid colony formation. In a second series of functional
      studies, HPCs treated with retinoic acid were induced to shift from erythroid to
      granulocytic differentiation (Labbaye et al. 1994. Blood. 83:651-656); this was
      coupled with abrogation of GATA-1, NF-E2, and EpR expression and conversely
      enhanced GATA-2 levels. These results indicate the expression and key role of
      GATA-2 in the early stages of HPC proliferation/differentiation. Conversely, NF
      E2 and GATA-1 expression and function are apparently restricted to erythroid
      differentiation and maturation: their expression precedes that of the EpR, and
      their function may be in part mediated via the EpR.

PMID- 7738200
TI  - A mutation in FBN1 disrupts profibrillin processing and results in isolated
      skeletal features of the Marfan syndrome.
AB  - Dermal fibroblasts from a 13-yr-old boy with isolated skeletal features of the
      Marfan syndrome were used to study fibrillin synthesis and processing. Only one
      half of the secreted profibrillin was proteolytically processed to fibrillin
      outside the cell and deposited into the extracellular matrix. Electron
      microscopic examination of rotary shadowed microfibrils made by the proband's
      fibroblasts were indistinguishable from control cells. Sequencing of the FBN1
      gene revealed a heterozygous C to T transition at nucleotide 8176 resulting in
      the substitution of a tryptophan for an arginine (R2726W), at a site immediately
      adjacent to a consensus sequence recognized by a cellular protease. Six other
      individuals in the proband's family had the FBN1 mutation that segregated with
      tall stature. None of the affected individuals have cardiac or ocular
      manifestations of the Marfan syndrome. This mutation identifies a putative site
      for profibrillin to fibrillin processing, and is associated with isolated
      skeletal features of the Marfan syndrome, indicating that the FBN1 gene is one of
      the genes that determines height in the general population. The cellular effect
      of the mutation may be equivalent to a "null" FBN1 allele and may define the
      phenotype associated with FBN1 "null" alleles.

PMID- 7738199
TI  - Muscle protein waste in tumor-bearing rats is effectively antagonized by a beta 2
      adrenergic agonist (clenbuterol). Role of the ATP-ubiquitin-dependent proteolytic
      pathway.
AB  - Tissue protein hypercatabolism (TPH) is a most important feature in cancer
      cachexia, particularly with regard to the skeletal muscle. The rat ascites
      hepatoma Yoshida AH-130 is a very suitable model system for studying the
      mechanisms involved in the processes that lead to tissue depletion, since it
      induces in the host a rapid and progressive muscle waste mainly due to TPH
      (Tessitore, L., G. Bonelli, and F. M. Baccino. 1987. Biochem. J. 241:153-159).
      Detectable plasma levels of tumor necrosis factor-alpha associated with marked
      perturbations in the hormonal homeostasis have been shown to concur in forcing
      metabolism into a catabolic setting (Tessitore, L., P. Costelli, and F. M.
      Baccino. 1993. Br. J. Cancer. 67:15-23). The present study was directed to
      investigate if beta 2-adrenergic agonists, which are known to favor skeletal
      muscle hypertrophy, could effectively antagonize the enhanced muscle protein
      breakdown in this cancer cachexia model. One such agent, i.e., clenbuterol,
      indeed largely prevented skeletal muscle waste in AH-130-bearing rats by
      restoring protein degradative rates close to control values. This normalization
      of protein breakdown rates was achieved through a decrease of the hyperactivation
      of the ATP-ubiquitin-dependent proteolytic pathway, as previously demonstrated in
      our laboratory (Llovera, M., C. Garcia-Martinez, N. Agell, M. Marzabal, F. J.
      Lopez-Soriano, and J. M. Argiles. 1994. FEBS (Fed. Eur. Biochem. Soc.) Lett.
      338:311-318). By contrast, the drug did not exert any measurable effect on
      various parenchymal organs, nor did it modify the plasma level of corticosterone
      and insulin, which were increased and decreased, respectively, in the tumor
      hosts. The present data give new insights into the mechanisms by which
      clenbuterol exerts its preventive effect on muscle protein waste and seem to
      warrant the implementation of experimental protocols involving the use of
      clenbuterol or alike drugs in the treatment of pathological states involving TPH,
      particularly in skeletal muscle and heart, such as in the present model of cancer
      cachexia.

PMID- 7738201
TI  - Modulation of skeletal muscle sodium channels by human myotonin protein kinase.
AB  - In myotonic muscular dystrophy, abnormal muscle Na currents underlie myotonic
      discharges. Since the myotonic muscular dystrophy gene encodes a product, human
      myotonin protein kinase, with structural similarity to protein kinases, we tested
      the idea that human myotonin protein kinase modulates skeletal muscle Na
      channels. Coexpression of human myotonin protein kinase with rat skeletal muscle
      Na channels in Xenopus oocytes reduced the amplitude of Na currents and
      accelerated current decay. The effect required the presence of a potential
      phosphorylation site in the inactivation mechanism of the channel. The mutation
      responsible for human disease, trinucleotide repeats in the 3' untranslated
      region, did not prevent the effect. The consequence of an abnormal amount of the
      kinase would be altered muscle cell excitability, consistent with the clinical
      finding of myotonia in myotonic dystrophy.

PMID- 7738202
TI  - The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in
      human ovarian cancer.
AB  - Chemokines may control the macrophage infiltrate found in many solid tumors. In
      human ovarian cancer, in situ hybridization detected mRNA for the macrophage
      chemokine monocyte chemoattractant protein-1 (MCP-1) in 16/17 serous carcinomas,
      4/4 mucinous carcinomas, 2/2 endometrioid carcinomas, and 1/3 borderline tumors.
      In serous tumors, mRNA expression mainly localized to the epithelial areas, as
      did immunoreactive MCP-1 protein. In the other tumors, both stromal and
      epithelial expression were seen. All tumors contained variable numbers of cells
      positive for the macrophage marker CD68. MCP-1 mRNA was also detected in the
      stroma of 5/5 normal ovaries. RT-PCR demonstrated mRNA for MCP-1 in 7/7 serous
      carcinomas and 6/6 ovarian cancer cell lines. MCP-1 protein was detected by ELISA
      in ascites from patients with ovarian cancer (mean 4.28 ng/ml) and was produced
      primarily by the cancer cells. Human MCP-1 protein was also detected in culture
      supernatants from cell lines and in ascites from human ovarian tumor xenografts
      which induce a peritoneal monocytosis in nude mice. We conclude that the
      macrophage chemoattractant MCP-1 is produced by epithelial ovarian cancer and
      that the tumor cells themselves are probably a major source. MCP-1 may contribute
      to the accumulation of tumor-associated macrophages, which may subsequently
      influence tumor behavior.

PMID- 7738203
TI  - A major histocompatibility complex class I-related Fc receptor for IgG on rat
      hepatocytes.
AB  - Intestinal epithelial cells of the neonatal rat and mouse have been shown to
      express a major histocompatibility complex (MHC) class I-like Fc receptor, or
      FcRn, which transports IgG in an apical to basolateral direction. Previous
      studies have suggested the possible expression of this receptor beyond the
      neonatal period within the liver. Since bile contains high levels of IgG, we
      sought to determine whether the FcRn was functionally expressed by adult rat
      hepatocytes. Using primers specific for FcRn, which did not cross hybridize with
      MHC class I transcripts, FcRn DNA was amplified by reverse transcriptase
      polymerase chain reaction from RNA of adult rat hepatocytes. This RNA contained
      functional FcRn transcripts as it encoded a beta 2-microglobulin-associated cell
      surface protein as determined by immunoprecipitation of biotinylated cell surface
      proteins with a polyclonal anti-FcRn specific antiserum. Western blotting of
      hepatocyte canalicular (apical) and sinusoidal (basolateral) plasma membranes
      with an FcRn-specific monoclonal antibody further confirmed the protein
      expression and suggested that FcRn was enriched on the canalicular surface
      membranes. FcRn, on the surface of hepatocytes, was biologically functional as it
      bound Fc fragments of IgG at pH 6.0 but not 8.0, which is the same pH dependence
      observed for FcRn in rat neonatal enterocytes. Thus, FcRn is functionally
      expressed outside of the neonatal period on the canalicular cell surface of adult
      hepatocytes. This suggests that hepatocyte FcRn may bind luminal IgG, providing a
      potential functional communication between parenchymal immune cells and bile.

PMID- 7738205
TI  - Increased adipose tissue expression of tumor necrosis factor-alpha in human
      obesity and insulin resistance.
AB  - Obesity is frequently associated with insulin resistance and abnormal glucose
      homeostasis. Recent studies in animal models have indicated that TNF-alpha plays
      an important role in mediating the insulin resistance of obesity through its
      overexpression in fat tissue. However, the mechanisms linking obesity to insulin
      resistance and diabetes in humans remain largely unknown. In this study we
      examined the expression pattern of TNF-alpha mRNA in adipose tissues from 18
      control and 19 obese premenopausal women by Northern blot analysis. TNF-alpha
      protein concentrations in plasma and in conditioned medium of explanted adipose
      tissue were measured by ELISA. Furthermore, the effects of weight reduction by
      dietary treatment of obesity on the adipose expression of TNF-alpha mRNA were
      also analyzed in nine premenopausal obese women, before and after a controlled
      weight-reduction program. These studies demonstrated that obese individuals
      express 2.5-fold more TNF-alpha mRNA in fat tissue relative to the lean controls
      (P < 0.001). Similar increases were also observed in adipose production of TNF
      alpha protein but circulating TNF-alpha levels were extremely low or
      undetectable. A strong positive correlation was observed between TNF-alpha mRNA
      expression levels in fat tissue and the level of hyperinsulinemia (P < 0.001), an
      indirect measure of insulin resistance. Finally, body weight reduction in obese
      subjects which resulted in improved insulin sensitivity was also associated with
      a decrease in TNF-alpha mRNA expression (45%, P < 0.001) in fat tissue. These
      results suggest a role for the abnormal regulation of this cytokine in the
      pathogenesis of obesity-related insulin resistance.

PMID- 7738204
TI  - Glucose modulates rat substantia nigra GABA release in vivo via ATP-sensitive
      potassium channels.
AB  - Glucose modulates beta cell insulin secretion via effects on ATP-sensitive
      potassium (KATP) channels. To test the hypothesis that glucose exerts a similar
      effect on neuronal function, local glucose availability was varied in awake rats
      using microdialysis in the substantia nigra, the brain region with the highest
      density of KATP channels. 10 mM glucose perfusion increased GABA release by 111
      +/- 42%, whereas the sulfonylurea, glipizide, increased GABA release by 84 +/-
      20%. In contrast, perfusion of the KATP channel activator, lemakalim, or
      depletion of ATP by perfusion of 2-deoxyglucose with oligomycin inhibited GABA
      release by 44 +/- 8 and 45 +/- 11%, respectively. Moreover, the inhibition of
      GABA release by 2-deoxyglucose and oligomycin was blocked by glipizide. During
      systemic insulin-induced hypoglycemia (1.8 +/- 0.3 mM), nigral dialysate GABA
      concentrations decreased by 49 +/- 4% whereas levels of dopamine in striatal
      dialysates increased by 119 +/- 18%. We conclude that both local and systemic
      glucose availability influences nigral GABA release via an effect on KATP
      channels and that inhibition of GABA release may in part mediate the
      hyperexcitability associated with hypoglycemia. These data support the hypothesis
      that glucose acts as a signaling molecule, and not simply as an energy-yielding
      fuel, for neurons.

PMID- 7738207
TI  - Atrial natriuretic peptide and its potential role in pharmacotherapy.
AB  - Atrial natriuretic peptide (ANP) is a 28 amino-acid polypeptide secreted into the
      blood by atrial myocytes after atrial pressure and distension. Although its role
      in humans is not clear, it can produce a variety of physiologic effects including
      vasodilatation, natriuresis, and suppression of the renin-angiotensin-aldosterone
      axis. These actions are potentially useful in a variety of pathologic states such
      as hypertension and congestive heart failure, and diverse methods to augment the
      effects of ANP in these states have been devised. The results are exciting and,
      despite some problems, may lead to the pharmacologic use of enhancement of ANP
      actions in several clinical disorders.

PMID- 7738206
TI  - Peptide-mediated inactivation of recombinant and platelet plasminogen activator
      inhibitor-1 in vitro.
AB  - Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of tissue-type
      plasminogen activator (t-PA) and urokinase plasminogen activator, is an important
      regulator of the blood fibrinolytic system. Elevated plasma levels of PAI-1 are
      associated with thrombosis, and high levels of PAI-1 within platelet-rich clots
      contribute to their resistance to lysis by t-PA. Consequently, strategies aimed
      at inhibition of PAI-1 may prove clinically useful. This study was designed to
      test the hypothesis that a 14-amino acid peptide, corresponding to the PAI-1
      reactive center loop (residues 333-346), can rapidly inhibit PAI-1 function. PAI
      1 (0.7 microM) was incubated with peptide (55 microM) at 37 degrees C. At timed
      intervals, residual PAI-1 activity was determined by addition of reaction mixture
      samples to t-PA and chromogenic substrate. The T1/2 of PAI-1 activity in the
      presence of peptide was 4 +/- 3 min compared to a control T1/2 of 98 +/- 18 min.
      The peptide also inhibited complex formation between PAI-1 and t-PA as
      demonstrated by SDS-PAGE analysis. However, the capacity of the peptide to
      inhibit PAI-1 bound to vitronectin, a plasma protein that stabilizes PAI-1
      activity, was markedly attenuated. Finally, the peptide significantly enhanced in
      vitro lysis of platelet-rich clots and platelet-poor clots containing recombinant
      PAI-1. These results indicate that a 14-amino acid peptide can rapidly inactivate
      PAI-1 and accelerate fibrinolysis in vitro. These studies also demonstrate that
      PAI-1 function can be directly attenuated in a physiologic setting and suggest a
      novel approach for augmenting fibrinolysis in vivo.

PMID- 7738208
TI  - Drugs and endogenous ligands compete for receptor occupancy.
AB  - Dietary and endogenous ligands compete with drugs for receptor occupancy and
      therefore should be considered during therapeutic interventions and during
      pharmacokinetic/pharmacodynamic modeling. When disease is the result of an
      overabundance of these natural ligands, antibodies and/or their Fab fragments may
      be useful as therapeutic agents to reverse the effects of the natural ligands.

PMID- 7738209
TI  - Using the electrocardiogram to teach clinical pharmacology.

PMID- 7738210
TI  - Primary care physicians and the cost of drugs: a study of prescribing practices
      based on recognition and information sources.
AB  - Rapidly inflating health care costs limit patient care, and prescription drug
      costs constitute a major component of this expenditure. This study examines
      attitudes toward and knowledge of prescription drug costs of primary care
      physicians. Access to information about drug costs and implications for medical
      education are also explored. A questionnaire survey was sent to 137 internists,
      family, and general practitioners, randomly selected from a list provided by the
      Ohio State Medical Board. The questionnaire elicited information on demographic
      characteristics of respondents, influence of drug costs on prescribing habits,
      actual knowledge of prices of the 20 most commonly used drugs, attitudes toward
      generic drug use, sources of information on costs, and desire for emphasis on
      drug costs in medical education. Responding physicians indicated consideration of
      drug costs in therapeutic decisions, but lacked information and often made
      inaccurate assumptions about costs of drugs prescribed. Most felt they could
      provide better service and reduce costs if information about drug prices was
      readily available. Most agreed medical education should address drug costs. Drug
      cost estimates varied widely; correct responses ranged from 9% to 53%. No
      statistically significant pattern emerged regarding demographics of respondents
      or information sources used. Primary care physicians consider drug costs
      important and realize that cost-effective prescribing may lower health care
      costs. However, because physician knowledge of drug costs is inadequate and costs
      are not readily accessible, implications for better physician education and
      improved abscess are substantial.

PMID- 7738212
TI  - Sequential monotherapy of hypertension.
AB  - In most cases, the antihypertensive therapy for an individual patient is selected
      through a process of trial and error. This study determined if, by treating each
      hypertensive patient sequentially, with six antihypertensive drugs, one from each
      of the major classes, one could decide on the best possible drug for control of
      hypertension. In a randomized open-label crossover study, 19 patients (16 male
      and 3 female), 28-70 years of age with a sitting diastolic blood pressure of 95
      110 mm Hg were given atenolol, captopril, clonidine, indapamide, prazosin, and
      verapamil in a sequential manner. Each drug was started at the minimum
      recommended or lower dose and titrated upwards every 2 weeks, if well tolerated,
      until blood pressure was controlled (diastolic BP < 90 mm Hg). If blood pressure
      was controlled, the drug was continued for another 2 weeks. A washout period of
      at least 2 weeks was allowed between drugs. Both systolic and diastolic blood
      pressures were reduced significantly with all of the six drugs. In 18 of the 19
      patients, blood pressure was controlled with at least one of six drugs,
      frequently with the lowest dose. The authors conclude that if hypertension is not
      controlled with the lowest recommended dose of a drug, other antihypertensive
      drugs should be tried sequentially rather than increasing the dose or adding a
      second drug.

PMID- 7738211
TI  - Calcium-channel entry blocker therapy for hypertensive patients with concomitant
      renal impairment: a focus on isradipine.
AB  - In the treatment of hypertension in renally impaired patients, normalization of
      blood pressure alone may not be sufficient to prevent significant morbidity to
      the kidneys. Treatment must reduce pressure in the renal vasculature, otherwise
      glomerular filtration rate and renal plasma flow will continue to deteriorate.
      Isradipine a dihydropyridine calcium-channel blocker, has been investigated as a
      suitable treatment in this setting. Isradipine maintains glomerular filtration
      rate, preserves or enhances renal plasma flow, decreases renal vascular
      resistance, maintains or reduces filtration fraction, and exerts a sustained
      natriuretic effect, all of which may enable isradipine to slow the rate of
      progression of renal deterioration. In addition, isradipine may decrease
      proteinuria and may decrease glomerular capillary pressure by dilating both the
      efferent and afferent arterioles. Unlike older calcium-channel blockers,
      isradipine exhibits minimal cardiodepressant activity and is not associated with
      any negative inotropic effects. It is metabolized in the liver and dosage
      adjustments may not be necessary when administered to patients with renal
      insufficiency. Isradipine has a favorable renal effect profile and also has
      several properties that meet the requirements of other patient populations where
      an extra measure of antihypertensive safety is required, such as diabetics,
      dialysis patients, and transplant recipients. Side effects with isradipine are
      usually mild and transient, occurring in a dose-dependent manner.

PMID- 7738213
TI  - Inhibition of angiotensin-converting enzyme with libenzapril in normotensive
      males.
AB  - The effect of intravenous (i.v.) libenzapril was studied in six healthy males by
      administering i.v. angiotensin I (AI) administered in stepwise increments of 20
      ng/kg/5 min until the subjects' systolic blood pressure (SBP) had increased 20-30
      mm Hg above baseline. The mean baseline infusion of 63 ng/kg/5 min resulted in a
      significant (P < 0.05) increase in the ratio of AII to AI plasma levels from 0.52
      +/- 0.46 to 7.92 +/- 4.48 and a SBP increase of 120 +/- 7.1 to 147 +/- 5.6.
      Within 15 minutes of starting the 1-mg infusion of libenzapril over 1.5 hours,
      the AII/AI ratio decreased to baseline values, and the SBP had returned to
      baseline in 1 hour. Repeat AI challenges at 3.5 and 5 hours postdose did not
      increase SBP significantly. Even the 6.5-hour challenge demonstrated only a
      slight increase in SBP, with an AII/AI ratio of 0.26. At 24 hours, SBP was only
      40% of the baseline response, demonstrating that libenzapril is a potent long
      acting ACE inhibitor.

PMID- 7738214
TI  - A dose-ranging pharmacokinetics study of sodium diethyldithiocarbamate in normal
      healthy volunteers.
AB  - Sodium diethyldithiocarbamate (DDTC) is an investigational modulator of the
      toxicity produced by cisplatin. The pharmacokinetics of DDTC were evaluated after
      administration of 200 mg/m2/hr (n = 8) and 400 mg/m2/hr (n = 7) DDTC as 4-hour
      intravenous infusions to normal male healthy volunteers. Diethyldithiocarbamate
      concentration at steady-state (Cpss) increased disproportionally from 27.0 +/-
      7.6 microM for the low dose to 74.8 +/- 19.3 microM for the high dose, whereas
      total body clearance decreased from 23.83 +/- 8.23 mL/min/kg for the low dose to
      15.48 +/- 2.72 mL/min/kg for the high dose (P < 0.05). However, the volume of
      distribution in the terminal phase remained unchanged. Diethyldithiocarbamate
      terminal elimination half-life (t1/2 beta) increased from 3.74 +/- 1.10 minutes
      for the low dose to 6.08 +/- 1.07 minutes for the high dose (P < 0.005). The data
      were then fitted using a one-compartment open model with zero-order infusion and
      Michaelis-Menten elimination kinetics. The Km for DDTC was estimated to be 124.3
      +/- 19.9 microM, whereas the Vm was estimated to be 3.67 +/- 1.15 mumol/min/kg.
      However, DDTC t1/2 beta was independent of DDTC concentrations, suggesting that
      the nonlinearity in DDTC kinetics does not exactly follow Michaelis-Menten
      elimination kinetics. Thus, DDTC pharmacokinetics are dose dependent and may not
      be concentration dependent. Clinically, DDTC Cpss will increase nonlinearly with
      an increase in dose.

PMID- 7738215
TI  - Pharmacodynamics of bolus famotidine versus infused cimetidine, ranitidine, and
      famotidine.
AB  - A four-way crossover pilot study was conducted to compare the pharmacodynamic
      response of intermittent famotidine (20 mg every 12 hr) to continuous infusions
      of cimetidine (1200 mg/24 hr), ranitidine (150 mg/24 hr), and famotidine (40
      mg/24 hr) in six normal male volunteers. Intragastric pH was monitored
      continuously for 24 hours. Comparisons included percent time during the 24-hour
      period that gastric pH was greater than pH 4.0, and pH 5.0, and also for the
      steady-state period of each regimen (12-24 hr). Although no statistically
      significant difference was observed for any of these comparisons, a clinically
      relevant trend was observed. In crossover experiments, famotidine intermittent
      infusions provided gastric pH readings above 4.0 and 5.0 for a longer duration
      than any of the continuous infusion regimens. Famotidine intermittent infusion
      regimens (20 mg every 12 hr) are at least equivalent to continuous infusions of
      cimetidine, ranitidine, and famotidine. Based on these findings, comparative
      studies in an appropriate critical care population would be beneficial, but any
      such studies must use a crossover design because of the even higher degree of
      intersubject variance in pH control. For this reason, the normal volunteer
      crossover model used here may provide important comparative information for the
      various regimens used in suppression of gastric acidity.

PMID- 7738216
TI  - Pharmacokinetics of famciclovir in subjects with chronic hepatic disease.
AB  - The pharmacokinetic profile of penciclovir was determined after a single 500-mg
      dose of its oral precursor, famciclovir, in 9 healthy volunteers and in 14
      patients with chronic hepatic disease. Plasma and urine samples were analyzed for
      concentrations of penciclovir and 6-deoxy-penciclovir using a reverse-phase high
      performance liquid chromatography (HPLC) method. Famciclovir was not quantifiable
      in patients with hepatic disease, and 6-deoxy-penciclovir was quantifiable in
      only a limited number of specimens. The extent of systemic availability of
      penciclovir, as measured by AUC0-infinity, was similar in patients with hepatic
      disease and in healthy subjects. In contrast, Cmax was significantly lower
      (average decrease of 43%) in subjects with hepatic disease relative to healthy
      normal subjects. Median Tmax for subjects with hepatic disease was significantly
      increased (by 0.75 hours) compared with subjects with normal liver function.
      These data suggest a decrease in the rate, but not the extent, of systemic
      availability of penciclovir in patients with hepatic disease. It should be
      unnecessary to modify the dose of famciclovir for subjects with compensated
      hepatic disease and normal renal function.

PMID- 7738217
TI  - Pharmacokinetics of tazobactam M1 metabolite after administration of
      piperacillin/tazobactam in subjects with renal impairment.
AB  - Tazobactam is a new derivative of penicillinic acid sulfone, which functions as
      an irreversible inhibitor of many beta-lactamases. The disposition of tazobactam
      M1 metabolite after intravenous (i.v.) infusion of 3 g of piperacillin/0.375 g of
      tazobactam was evaluated in 26 subjects with various degrees of renal impairment.
      Participants in the study were 18 subjects with creatinine clearances (ClCR)
      ranging from 7.4-41.8 mL/min, 4 subjects maintained on continuous ambulatory
      peritoneal dialysis (CAPD), and 4 subjects undergoing chronic hemodialysis (HD).
      The pharmacokinetic parameters of piperacillin and tazobactam were evaluated and
      were similar to previous reports. Tazobactam M1 metabolite maximum plasma
      concentration increased as renal function declined. The terminal elimination half
      life and area under the plasma concentration-time curve of the tazobactam M1
      metabolite increased as renal function declined. The mean rate of recovery of the
      tazobactam M1 metabolite in hemodialysate during a 3- to 4.2-hour HD session 1
      hour after the i.v. infusion of piperacillin/tazobactam was 25.3%. However, when
      HD was performed at 36-48 hours after the i.v. infusion, 57.6% of the tazobactam
      dose was recovered as M1 metabolite, suggesting further conversion of tazobactam
      to M1 metabolite. Peritoneal dialysis removed 15.8% (n = 2) of the tazobactam
      dose as the M1 metabolite. Using a dose of 3 g of piperacillin/0.375 g of
      tazobactam, the predicted maximum steady-state plasma concentrations of the
      tazobactam M1 metabolite are 14.6 micrograms/mL, 34.8 micrograms/mL, and 48.8
      micrograms/mL for subjects with ClCR 20-40 mL/min (every 6 hour dosing), ClCR <
      20 mL/min (every 8 hour dosing), and on CAPD (every 12 hour dosing),
      respectively.

PMID- 7738218
TI  - Absorption of isosorbide-5-mononitrate at specific sites in the gastrointestinal
      tract.
AB  - As part of a development program for controlled- and extended-release
      formulations of isosorbide-5-mononitrate (ISMN), the rate and extent of drug
      absorption was evaluated after site-specific delivery in the gastrointestinal
      (GI) tract. Seven healthy male subjects received, on separate occasions, 20 mg of
      ISMN solution orally and via nasogastric tube to the jejunum, terminal ileum, and
      ascending colon. Compared with oral administration (AUC 2,963 hr x ng/mL, Cmax
      442 ng/mL, Tmax 0.81 hr), placement of drug directly into the jejunum did not
      change the extent (AUC 2,844 hr x ng/mL) but increased the rate of absorption
      (Cmax 630 ng/mL, Tmax 0.28 hr) due to direct placement of drug into the
      intestine. Administration to the terminal ileum resulted in a rate of absorption
      comparable to that from the jejunum (Tmax 0.28 hr) but a reduction in extent
      (mean AUC 2,377 hr x ng/mL). Delivery to the ascending colon resulted in a
      further decrease in the extent (AUC 2,017 hr x ng/mL) and a "slowing" of the rate
      of absorption compared with the two intestinal sites (Cmax 392 ng/mL, Tmax 0.68
      hr). Overall, bioavailability throughout the GI tract was sufficient to support
      development of controlled- and extended-release formulations.

PMID- 7738219
TI  - In vitro prediction of the terfenadine-ketoconazole pharmacokinetic interaction.
AB  - Biotransformation of the peripherally acting H-1 histamine antagonist,
      terfenadine, to its desalkyl and hydroxy metabolites was studied in vitro using
      microsomal preparations from six separate human livers. These metabolic reactions
      are mediated by the specific cytochrome P450-3A4. Addition of ketoconazole to the
      reaction mixtures reduced the rate of formation of both metabolites in a manner
      consistent with competitive inhibition. Ketoconazole inhibition constants (Ki)
      averaged 0.024 microM for the desalkyl terfenadine pathway, and 0.237 microM for
      the hydroxy terfenadine pathway. A mathematical model, based on the in vitro Ki
      values and the usual clinical range of plasma ketoconazole concentrations (1-5
      micrograms/mL; 1.88-0.94 microM), predicted that plasma terfenadine levels during
      coadministration of ketoconazole would increase by a factor ranging from 13-fold
      to 59-fold relative to the same dose of terfenadine given without ketoconazole.
      Actual plasma terfenadine levels during terfenadine-ketoconazole coadministration
      in a clinical pharmacokinetic study were close to those predicted by the model.
      These plasma levels were associated with prolongation of the corrected QT
      interval, thereby explaining the potentially life-threatening ventricular
      arrhythmias reportedly associated with terfenadine-ketoconazole cotherapy. Thus,
      data from studies of drug metabolism in vitro can be used to predict and thereby
      possibly avoid clinically important drug interactions.

PMID- 7738220
TI  - Improving the diagnosis of hypersensitivity reactions associated with
      sulfonamides.
AB  - The differential diagnosis of idiosyncratic adverse drug reactions (ADRs) is
      difficult because symptoms are seldom pathognomonic. The authors compared the
      performance of two new diagnostic aids in the differential diagnosis of 27 cases
      of skin reactions associated with sulfonamide therapy. One test, the Bayesian
      Adverse Reaction Diagnostic Instrument (BARDI), calculates the posterior
      probability (PsP) of a drug being the etiology of an idiosyncratic ADR. The
      other, the lymphocyte toxicity assay (LTA), is a biochemical test that determines
      the percent of cell death because of toxic metabolites of a drug. Cases were
      assessed independently and blindly by BARDI and then the LTA. Skin reactions
      consisted of 19 exanthematous eruptions, 2 vasculitis, 1 erythema multiforme, and
      5 urticarial rashes. BARDI indicated that the drug was very likely associated
      with 20 adverse events (PsP = 0.59 to 0.99); and unlikely to have caused 7 (PsP =
      0.02 to 0.38). The LTA showed that 19 patients (70%) were test positive, and 8
      were test negative. Comparing BARDI to LTA showed that BARDI had 79% sensitivity
      and 67% accuracy, but only 38% specificity. However, when the results of the LTA
      were incorporated into the calculation of the PsP based on this comparison, BARDI
      indicated that the drug was very likely associated with 18 reactions (PsP = 0.61
      to 0.99) and unlikely to have caused 9 reactions (PsP = 0.003 to 0.47). The
      agreement increased from 67% to 96%. These findings indicate that the accuracy of
      diagnosis of idiosyncratic ADRs improved when the results of BARDI and LTA were
      combined. These findings also crossvalidate the results obtained by using BARDI.

PMID- 7738221
TI  - Pyrazinoylguanidine downregulates the glucose fatty-acid cycle in hypertensive,
      hyperinsulinemic diabetic patients.
AB  - Eight hypertensive patients with noninsulin dependent diabetes mellitus (NIDDM)
      were administered the experimental drug pyrazinoylguanidine (PZG) either alone or
      in combination with calcium-channel or beta-blockers. This treatment appeared to
      "downregulate" the glucose fatty acid cycle and reduced both systolic and
      diastolic blood pressures and mean body weight. Patients served as their own
      controls in this dose-escalation study, which included placebo treatment
      (baseline) 3 weeks, 300 mg PZG for 3 weeks and 600 mg for 3 weeks. PZG reduced
      increased serum concentrations of free fatty acids (FFA), glucose, and
      triglycerides (TG). TG concentrations correlated inversely with serum HDL
      cholesterol concentrations. The beta-blockers used by several patients increased
      their FFA, glucose, insulin and TG concentrations, as well as blunting their
      response to PZG. The calcium-channel blockers exerted these effects to a much
      lesser extent. PZG reduced or abolished glycosuria, related to PZG's capacity to
      decrease hyperglycemia. Withdrawal of PZG restored glycosuria, as blood sugar
      increased. PZG was well tolerated. No patient reported any adverse effect or
      missed a weekly clinic visit (12 weeks). PZG deserves further study as
      supplementary and/or replacement therapy in NIDDM patients who are hypertensive
      and hyperlipidemic.

PMID- 7738222
TI  - New understandings of the pathogenesis of acne.

PMID- 7738223
TI  - Acne: acute or chronic disease?

PMID- 7738224
TI  - The psychosocial impact of acne: patients' perceptions.

PMID- 7738225
TI  - The treatment of acne: the role of combination therapies.

PMID- 7738226
TI  - Patient compliance: enhancing clinician abilities and strategies.

PMID- 7738227
TI  - Treatment of acne in the fee-for-service and managed care settings.

PMID- 7738228
TI  - The evaluation and management of acne: economic considerations.

PMID- 7738229
TI  - The many faces of acne.

PMID- 7738230
TI  - Milk intake, growth and energy consumption in pups of ice-breeding grey seals
      (Halichoerus grypus) from the Gulf of St. Lawrence, Canada.
AB  - In this study we document growth, milk intake and energy consumption in nursing
      pups of ice-breeding grey seals (Halichoerus grypus). Change in body composition
      of the pups, change in milk composition as lactation progresses, and mass
      transfer efficiency between nursing mothers and pups are also measured. Mass
      transfer efficiency between mother-pup pairs (n = 8) was 42.5 +/- 8.4%. Pups were
      gaining a daily average of 2.0 +/- 0.7 kg (n = 12), of which 75% was fat, 3%
      protein and 22% water. The total water influx was measured to be 43.23 +/- 8.07
      ml.kg-1.day-1. Average CO2 production was 0.85 +/- 0.20 ml.g-1.h-1, which
      corresponds to a field metabolic rate of 0.55 +/- 0.13 MJ.kg-1.day-1, or 4.5 +/-
      0.9 times the predicted basal metabolic rate based on body size (Kleiber 1975).
      Water and fat content in the milk changed dramatically as lactation progressed.
      At day 2 of nursing, fat and water content were 39.5 +/- 1.9% and 47.3 +/- 1.5%,
      respectively, while the corresponding figures for day 15 were 59.6 +/- 3.6% fat
      and 28.4 +/- 2.6% water. Protein content of the milk remained relatively stable
      during the lactation period with a value of 11.0 +/- 0.8% at day 2 and 10.4 +/-
      0.3% at day 15. Pups drank an average of 3.5 +/- 0.9 kg of milk daily,
      corresponding to a milk intake of 1.75 kg per kg body mass gained. The average
      daily energy intake of pups was 82.58 +/- 19.80 MJ, while the energy built up
      daily in the tissue averaged 61.72 +/- 22.22 MJ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738231
TI  - Secretion of electrolytes, protein and urea by the mandibular gland of the common
      wombat (Vombatus ursinus).
AB  - Saliva was collected from the mandibular glands of anaesthetized common wombats
      (Vombatus ursinus) to ascertain maximal flow rates, salivary composition and
      possible adaptations, particularly PO4(3-) secretion, to assist digestion. After
      temporary catheterization of the main duct through its oral opening, salivary
      secretion was evoked at flow rates ranging from 0.02 +/- 0.002 (+/- SEM) ml.min-1
      (0.7 +/- 0.07 microliter.min-1.kg body weight-1) to 0.4 +/- 0.05 ml.min-1 (14 +/-
      1.9 microliters.min-1.kg body weight-1) by ipsilateral intracarotid infusion of
      acetylcholine. The [Na+] (15 +/- 5.1 to 58 +/- 8.6 mmol.l-1) and [HCO3-] (35 +/-
      1.9 to 60 +/- 1.9 mmol.l-1) were positively correlated with salivary flow rate.
      The [K+] (58 +/- 5.2 to 30 +/- 2.4 mmol.l-1), [Ca2+] (10.4 +/- 1.67 to 4.1 +/-
      0.44 mmol.l-1), [Mg2+] (0.94 +/- 0.137 to 0.17 +/- 0.032 mmol.l-1), [Cl-] (71 +/-
      9.2 to 45 +/- 6.0 mmol.l-1), [urea] (9.3 +/- 0.79 to 5.1 +/- 0.54 mmol.l-1), H+
      activity (29 +/- 1.6 to 17 +/- 1.6 nEq.l-1) and amylase activity (251 +/- 57.4 to
      92 +/- 23.3 mu kat.l-1) were negatively correlated with flow. Both concentration
      and osmolality fell with increasing flow at the lower end of the flow range but
      osmolality always increased again by maximal flow whereas the relation between
      protein and flow was not consistent at the higher levels of flow and stimulation.
      Salivary [PO4(3+)] was not correlated with flow and at 3-14% of the plasma
      concentration was extremely low.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738233
TI  - Renal function at steady state in a toad (Bufo viridis) acclimated in
      hyperosmotic NaCl and urea solutions.
AB  - Kidney function of the euryhaline toad Bufo viridis was studied in animals
      acclimated to tap water and solutions of NaCl (230 and 500 mosmol.kg-1 H2O) and
      urea (500 mmol.l-1) in steady-state conditions. An ureter was catheterized for
      continuous urine collection and blood was sampled from an iliac artery. A single
      injection of 3H-inulin served for estimation of glomerular filtration rate: this
      was in the range of 15-27 ml.kg-1.h-1 and did not differ significantly in any of
      the acclimation conditions. Urine flow, on the other hand, varied considerably
      and was highest in tap water (18.2 +/- 3.2 ml.kg-1.h-1; urine/plasma inulin ratio
      = 0.88), lower in 230 mosmol.kg-1 H2O NaCl solution (13.5 +/- 3.9 ml.kg-1.h-1;
      u/p inulin ratio = 1.73) and lowest in 500 mosmol.kg-1 H2O NaCl or urea
      acclimation solutions (5-7 ml.kg-1.h-1; u/p inulin = 3.7-4.2). Clearance of free
      water was high in the tap water group, lower in 230 mosmol.kg-1 H2O NaCl
      solution, and much lower in the hyperosmotic acclimation conditions. Clearances
      of both Na+ and Cl- were similar under our experimental conditions, but changed
      independently in accordance to the composition of the acclimation solution.
      Potassium clearance was similar in all acclimation conditions, and a constant
      plasma K+ concentration was maintained. Urea clearance was high in tap water and
      500 mmol.l-1 urea acclimation groups and low in the NaCl acclimations.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7738232
TI  - The energetics of the common mole rat Cryptomys, a subterranean eusocial rodent
      from Zambia.
AB  - Body temperature, oxygen consumption, respiratory and cardiac activity and body
      mass loss were measured in six females and four males of the subterranean Zambian
      mole rat Cryptomys sp. (karyotype 2 n = 68), at ambient temperatures between 10
      and 35 degrees C. Mean body temperature ranged between 36.1 and 33.2 degrees C at
      ambient temperatures of 32.5-10 degrees C and was lower in females (32.7 degrees
      C) than in males (33.9 degrees C) at ambient temperatures of 10 degrees C but did
      not differ at thermoneutrality (32.5 degrees C). Except for body temperature,
      mean values of all other parameters were lowest at thermoneutrality. Mean basal
      oxygen consumption of 0.76 ml O2.g-1.h-1 was significantly lower than expected
      according to allometric equations and was different in the two sexes (females:
      0.82 ml O2.g-1.h-1, males: 0.68 ml O2.g1.h-1) but was not correlated with body
      mass within the sexes. Basal respiratory rate of 74.min-1 (females: 66.min1,
      males: 87.min-1) and basal heart rate of 200.min-1 (females: 190.min-1, males:
      216.min-1) were almost 30% lower than predicted, and the calculated thermal
      conductance of 0.144 ml O2.g-1.h1.degrees C-1 (females: 0.153 ml O2.g-1.h
      1.degrees C-1, males: 0.131 ml O2.g-1.h-1.degrees C-1) was significantly higher
      than expected. The body mass loss in resting mole rats of 8.6-14.1%.day-1 was
      high and in percentages higher in females than in males. Oxygen consumption and
      body mass loss as well as respiratory and cardiac activity increased at higher
      and lower than thermoneutral temperatures. The regulatory increase in O2 demand
      below thermoneutrality was mainly saturated by increasing tidal volume but at
      ambient temperatures < or = 15 degrees C, the additional oxygen consumption was
      regulated by increasing frequency with slightly decreasing tidal volume.
      Likewise, the additional blood transport capacity was mainly effected by an
      increasing stroke volume while there was only a slight increase of heart
      frequency. In an additional field study, temperatures and humidity in different
      burrow systems have been determined and compared to environmental conditions
      above ground. Constant temperatures in the nest area 70 cm below ground between
      26 and 28 degrees C facilitate low resting metabolic rates, and high relative
      humidity minimizes evaporative water loss but both cause thermoregulatory
      problems such as overheating while digging. In 13-16 cm deep foraging tunnels,
      temperature fluctuations were higher following the above ground fluctuations with
      a time lag.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7738234
TI  - Protein and lipid utilization during fasting with shallow and deep hypothermia in
      the European hedgehog (Erinaceus europaeus).
AB  - We investigated whether the relative contributions of body protein and lipid
      reserves differ according to the level of energy expenditure in fasting animals.
      Protein and lipid utilization was therefore quantified and compared in hedgehogs
      which fasted with shallow and deep hypothermia, i.e. by exposure at 5 or 20
      degrees C ambient temperature. Body composition was determined for every 150-g
      decrease in mass throughout the experiment, allowing the calculation of
      regression lines between body mass (independent variable, x) and body composition
      (dependent variable, y: water, protein, neutral lipids, phospholipids and
      cholesterol). There were highly significant (P < 0.001) linear decreases in all
      body components with decreasing body mass in both groups of hedgehogs. Neutral
      lipids were the main component of the total body mass loss (54%) in fasted
      animals with shallow and deep hypothermia, percentages of water (26-30%) and
      protein (10-11%) being lower, and those of phospholipid and cholesterol
      negligible (< 0.5%). In spite of different levels in energy expenditure (2.54 and
      1.07 W.kg-1 in shallow- and deep-hypothermal fasting hedgehogs, respectively),
      the energy sources were identical in both groups, neutral lipid being the main
      fuel (91-92%) and body protein accounting for the remainder (8-9%). Prolonged
      fasting with shallow and deep hypothermia were marked by low alaninemia and
      glycemia, while plasma free fatty acids and beta-hydroxybutyrate were
      elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738235
TI  - Time-course of the polycythemic response in normoxic and hypoxic mice with high
      blood oxygen affinity induced by cyanate administration.
AB  - The Hb-O2 affinity and the erythropoietic response as a function of time were
      studied in mice treated with sodium cyanate for up to 2 months. Cyanate increased
      the Hb-O2 affinity in normoxic mice more than in chronically hypoxic mice. The
      hemoglobin concentration rose as a function of time both in normoxic and hypoxic
      conditions but reached higher levels in hypoxia. After 42 days of study (21 days
      of hypoxia) hemoglobin reached maximum levels and thereafter showed a plateau in
      both cyanate and control animals. It is concluded that a chronic left-shifted
      oxygen dissociation curve does not avoid the development of hypoxic polycythemia
      in mice. Moreover, prolonged cyanate administration potentiates the
      erythropoietic response to chronic hypoxia. Since polycythemia is an index of
      tissue hypoxia, the results show that the high hemoglobin affinity did not
      prevent tissue hypoxia in low PO2 conditions. Results showing beneficial effects
      of high hemoglobin oxygen affinity induced by cyanate based on acute hypoxic
      expositions should be cautiously interpreted with regard to their adaptive value
      in animals chronically exposed to natural or simulated hypoxia.

PMID- 7738236
TI  - Effects of water restriction during growth and adulthood on renal function of
      bobwhite quail, Colinus virginianus.
AB  - Renal function and osmoregulation were studied in bobwhite quail (Colinus
      virginianus) raised with unrestricted water (chronically unrestricted group) or
      restricted water (chronically restricted group). There was no difference in urine
      concentrating ability between adult and juvenile (3.5 or 7.5 week-old) quail. A
      filtration marker (polyethylene glycol) was infused into adult quail via osmotic
      minipumps and responses to the following regimens studied: ad libitum water
      intake, short-term (4-day) water restriction, and acute (1-day) dehydration
      (withdrawal of all drinking water). Chronically restricted quail had higher urine
      to-plasma ratios of polyethylene glycol and lower urine flow rates during short
      term restriction. A greater proportion of the reduction in urine flow rate during
      dehydration was attributable to enhanced tubular reabsorption, rather than
      reduced rates of filtration, in chronically restricted than in chronically
      unrestricted birds. Chronically restricted birds also had higher maximum urine-to
      plasma ratios of polyethylene glycol (but not higher urine osmolality). These
      differences occurred in the face of arginine vasotocin concentrations that were
      not different in the two groups of birds (approximately 15 pg.ml-1 during
      hydration, and 45 pg.ml-1 during water restriction or dehydration). These
      observations suggest that chronically restricted quail have an enhanced
      responsiveness of tubular reabsorption to dehydration, a finding consistent with
      previous observations of tubule hypertrophy and hyperplasia in these birds
      (Goldstein and Ellis 1991). Despite this, no difference was found in medullary
      cAMP levels, either basal or arginine vasotocin- or forskolin-stimulated, in the
      two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738237
TI  - Field studies show associations between pulsator characteristics and udder
      health.
AB  - Four different field studies including 64, 140, 850 and 180 herds were used to
      investigate the association between pulsator characteristics and udder health.
      The results indicate that the best udder health is found in herds with a d phase
      > 330 ms and a pulsation rate > 55 min-1. A d phase of < 250 ms was associated
      with significant elevation in bulk milk somatic cell count, a higher incidence of
      acute clinical mastitis and a higher frequency of cows having mastitis associated
      with major pathogens (mainly Staphylococcus aureus) as compared with a d phase of
      > 331 ms. There was also a significant positive association between a shorter d
      phase and a high incidence of teat lesions needing veterinary treatment. Herds
      having no such teat lesions had pulsators with significantly longer d phase than
      herds with teat lesions (300 ms v. 288 ms). These results strongly suggest that
      in high-line milking machines the d phase should not be as short as 250 ms and
      should preferably be approximately 300 ms, and the pulsation rate should be at
      least > 55 cycles min-1. There was a strong relationship between the effect of d
      phase and the rate of pulsation.

PMID- 7738238
TI  - Isolation and quantification of cholesterol oxides in dairy products by selected
      ion monitoring mass spectrometry.
AB  - A method for isolation, detection and quantification of cholesterol oxidation
      products based on solid phase extraction in combination with preparative HPLC and
      gas chromatography-mass spectrometry selected ion monitoring has been developed
      for dairy products. The isolation procedure had a high recovery and artifact
      formation was minimal, as shown by isotope labelling. The limits of detection
      ranged from 0.3 to 35 pg/microliters of the isomeric forms of 7
      hydroxycholesterol, 20 alpha-hydroxycholesterol, the isomeric forms of
      cholesterol-5,6-epoxides, cholestanetriol, 25-hydroxycholesterol and 7
      ketocholesterol corresponding to a limit of quantification of 2-6 ng oxysterol/g
      lipid in the dairy product, depending on the nature of the cholesterol oxidation
      product.

PMID- 7738239
TI  - Distribution of plasminogen activator in different fractions of bovine milk.
AB  - The type and relative amounts of plasminogen activator (PA) in different
      fractions of bovine milk obtained from 15 Holstein cows were examined. Raw milk
      was centrifuged to separate skim milk and a somatic cell pellet. PA was mainly
      localized within the casein fraction, being 42 times that in the serum, and in
      association with somatic cells. The predominant form of PA in milk casein was
      isolated from SDS-PAGE gel extracts and had a molecular mass of approximately 75
      kDa. Its activity was increased 4.1-fold (P < 0.01) in the presence of fibrin but
      was unaffected by the presence of amiloride, indicating that it was due to tissue
      PA. The predominant forms of PA associated with milk somatic cells were isolated
      from SDS-PAGE gel extracts and had molecular masses of approximately 30 and
      approximately 50 kDa. The activity of both proteins was unaffected by the
      presence of fibrin but was dramatically reduced by the presence of amiloride,
      indicating that they represented urokinase-PA.

PMID- 7738240
TI  - Effects of stage of lactation and somatic cell count on plasminogen activator
      activity in bovine milk.

PMID- 7738241
TI  - Effect of forage digestibility and type of concentrate on nutrient utilization by
      lactating dairy cattle.
AB  - Six lactating dairy cows were used in a three period, part balanced changeover
      design experiment to investigate the effects of forage digestibility and
      concentrate composition on the efficiency of nutrient utilization in lactating
      dairy cows. Six treatments comprising three forage regimens and two concentrate
      types (starch v. fibre) were examined in a 3 x 2 factorial design. The three
      forage regimens were high digestibility grass silage offered ad lib. (HA) or
      restricted to 6.5 kg dry matter/d (HR) and a low digestibility grass silage
      offered ad lib. (LA). Within each forage regimen animals were offered 10 kg/d of
      supplements containing either high-starch or high-fibre concentrations.
      Experimental periods lasted 28 d with a 10 d recording period, during which
      animal performance, ration digestibility and nitrogen and energy utilization were
      measured. Respiratory exchange measurements were made over a 72 h period using
      indirect open-circuit calorimetry. Throughout the experiment, there were no
      significant forage x concentrate interactions in any of the intake, production or
      nutrient utilization results. Milk yield was significantly influenced by forage
      regimen (24.1, 21.7 and 21.9 kg/d for HA, HR and LA respectively) and concentrate
      type (21.6 and 23.5 kg/d for high-starch and high-fibre respectively).
      Concentrate type also significantly influenced milk protein concentration (32.8
      and 30.9 g/kg for high-starch and high-fibre respectively). Forage regimen
      significantly influenced the efficiency of utilization of metabolizable energy
      (ME) for milk production (k1) with values of 0.62, 0.64 and 0.59 for HA, HR and
      LA respectively. Concentrate type had no significant effect on ME intake, heat
      production or k1, although animals receiving the high-fibre concentrates
      synthesized proportionately 0.11 more milk energy per unit of available energy
      (ME intake--heat production) than those receiving the high-starch concentrates.
      Interpolation of the values obtained with the two high digestibility forage
      regimens indicated that at similar ME intakes there was a trend towards a higher
      k1 with the diet based on high digestibility silage, and this was in line with
      the higher metabolizability of the overall diet with this silage.

PMID- 7738242
TI  - Microbiological and technological aspects of milks fermented by bifidobacteria.

PMID- 7738243
TI  - Effects of abomasal infusions of sodium caseinate, a hydrolysate of casein or a
      corresponding mixture of free amino acids on milk yield and composition in dairy
      cows.
AB  - The effects of the form in which amino acids are presented to the abomasum on the
      milk production of dairy cows receiving a basal diet of grass silage and a barley
      based supplement were examined in two experiments. Effects of abomasal infusions
      of sodium caseinate were compared with the effects of corresponding levels of
      either an enzymic hydrolysate of casein (Expt 1) or a corresponding mixture of
      free amino acids (FAA; Expt 2). In Expt 1, although the yield of protein in milk
      increased progressively with each level of infusion, the yields of protein were
      greater for the caseinate than for the hydrolysate. Again, in Expt 2, for milk
      protein yield, sodium caseinate was superior to FAA at the lower level of
      infusion. In both experiments, the hydrolysate and FAA treatments were associated
      with higher concentrations of fat in the milk. There were indications of
      differences in the pattern of secretion of glucagon between the caseinate and FAA
      treatments. It is concluded that the differences between treatments relate either
      to the kinetics of absorption of amino acid residues or to the action of
      bioactive peptides released during digestion of casein.

PMID- 7738244
TI  - Patterns of intramammary infection and clinical mastitis over a 5 year period in
      a closely monitored herd applying mastitis control measures.
AB  - The udder health of a research herd of between 160 and 220 Friesian cows run on a
      commercial basis has been monitored closely, including detailed bacteriological
      study, over 5 years. The five point mastitis control plan had been in use for
      several years prior to this study and was continued with minor alterations to the
      management of the plan, more detailed bacteriological monitoring and increased
      encouragement to apply it. It has proved possible to make a substantial
      improvement in the udder health of the herd. The percentage of infected cows fell
      from 21.9 to 12.0 and the percentage of infected quarters from 7.3 to 3.3. The
      main benefit has been a drastic reduction in the rate of clinical and subclinical
      mastitis caused by coagulase-positive staphylococci. However the total incidence
      of clinical mastitis did not change substantially, averaging around 30 cases/100
      cows per year. This was largely because environmental mastitis organisms were
      responsible for 65% of all clinical cases. The results showed marked differences
      in the patterns of infection due to the environmental mastitis pathogens, Gram
      negative bacteria and aesculin-hydrolysing streptococci, suggesting different
      mechanisms of invasion of the gland.

PMID- 7738245
TI  - Staphylococci in heifer mastitis before and after parturition.
AB  - Aseptic udder quarter secretion samples (n = 1112) from 200 mastitic and 65 non
      mastitic control heifers from 160 different farms were collected for
      bacteriological examination and in vitro antimicrobial susceptibility testing.
      Coagulase-negative staphylococci (CNS) were the most frequently isolated bacteria
      (57.8%). The percentage of Staphylococcus aureus was 20.1, of streptococci 11.3
      and of other pathogens 10.8. Staph. simulans, Staph. hyicus, Staph. xylosus and
      Staph. chromogenes were the most common CNS. Staph. simulans and Staph. hyicus
      were most frequently found in clinical samples after parturition, whereas other
      CNS were equally or more often found in control samples. Most CNS infections
      detected in the prepartum period were eliminated spontaneously or with antibiotic
      treatment during early lactation, but the infected quarters were more susceptible
      to new infection by other pathogens. Milk N-acetyl-beta-glucosaminidase
      activities were measured to monitor changes in inflammation. Among the CNS
      infections, N-acetyl-beta-glucosaminidase activities were highest for Staph.
      hyicus and lowest for Staph. xylosus in the lactating mammary gland of heifers.
      CNS were resistant to trimethoprim-sulphonamide, ampicillin and erythromycin.
      Staph. aureus was more resistant than CNS to beta-lactamase-sensitive
      penicillins.

PMID- 7738246
TI  - Dairy cow characteristics related to Staphylococcus aureus isolation from quarter
      samples.
AB  - A comprehensive description of the health status of 2406 cows in 28 herds was
      used to study complex interrelationships between Staphylococcus aureus occurrence
      and potential risk factors at the cow level over a broad spectrum of production
      conditions. The objective of the study was to characterize those cows shedding
      Staph. aureus in milk and to provide indications of possible causal relations
      that should be further explored. The estimates are expected to aid in providing
      valid and precise evaluations of results from cross sectional microbiological
      examination of bovine (quarter) milk samples. Staph. aureus were isolated at
      microbiological examination of quarter milk from 5.2, 13.5, 17.9 and 22.0% of
      1552, 490, 296 and 277 cows in lactations 1, 2, 3 and 4-9 respectively.
      Simultaneous isolation of other mastitis pathogens was not significantly
      associated with occurrence of Staph. aureus. Of the positive samples, 95% had a
      positive California mastitis test reaction. Among the clinical measures of udder
      health, only visibly abnormal milk combined with normal udder tissue was
      associated with increased occurrence of Staph. aureus, although not consistently.
      Prior antibiotic treatment for udder disorders was not significantly associated
      with Staph. aureus isolation. The occurrence of sole ulcers in multiple digits
      was consistently associated with Staph. aureus in the first lactation. Milk yield
      was involved in interactions with other pathogens isolated, prior veterinary
      disease treatment, body weight and season of calving. Strong herd-year effects
      were revealed. This, combined with the interactions, indicated that some herd
      specific factors were major determinants of Staph. aureus occurrence. The study
      indicated which cow characteristics should be taken into account in
      epidemiological analyses and causal interpretations of data from cross sectional
      microbiological examinations of dairy herds.

PMID- 7738247
TI  - Monospecificity of the antibodies to bovine alpha s1-casein fragment 140-149:
      application to the detection of bovine milk in caprine dairy products.
AB  - Comparison of the primary sequences of bovine, ovine and caprine alpha s1-casein
      shows a deletion of eight amino acid residues in the ovine casein region 141-148,
      which is identical in the bovine and caprine proteins except for a single
      difference in position 148 (Q or E). Polyclonal antibodies raised in rabbits
      against the bovine casein sequence 140-149 (QELAYFYPEL) appeared monospecific for
      bovine alpha s1-casein, since no antibody-antigen complex was formed with
      homologous ovine or caprine proteins. These antibodies remained unable to
      recognize the caprine sequence in the native protein even after extensive tryptic
      proteolysis. The lack of immunoreactivity of the antibodies against synthetic
      caprine alpha s1-casein peptide 138-149 (VNQELAYFYPQL) suggested that the
      glutamic acid residue in position 148 is essential for the antigenic character of
      the bovine peptide. From these observations, the use of these antibodies for the
      detection and quantitation of bovine milk present in ovine dairy products could
      be extended to caprine products.

PMID- 7738248
TI  - Effect of disease on length of productive life of French Holstein dairy cows
      assessed by survival analysis.
AB  - Data from a survey performed from 1986 to 1990 were analyzed to assess the
      effects of diseases on length of productive life of 3589 Holstein cows from 47
      herds, using a proportional hazard model. The probability of a cow being culled,
      or hazard function, was supposed to be the product of an unspecified baseline
      hazard function and log-linear, time-dependent explanatory variables that
      possibly influence culling rate (Cox's regression). The effect of 16 health
      events was studied according to lactation number of occurrence. The model
      included adjustments for effects of herd-year-season (considered to be random),
      month of calving, stage of lactation, lactation number, reproductive performance,
      and milk production. The probability of a cow being culled increased in early and
      late stages of lactation in older cows, in low producing cows, and in cows with
      poor reproductive performance. Mastitis before the peak of lactation or during
      the dry period increased the risk (relative culling rate in first lactation, 1.3
      and 4.0, respectively). Teat injuries and nontraumatic udder disorders had a
      large impact on longevity. Cows with late metritis or early abortion had poor
      survival. The decrease in median length of productive life could be over a
      standard lactation in particular cases. Expected survivor curves, computed after
      assumption of a priori values of covariates and their evolution over time, appear
      to be powerful tools for examining the effect of health disorders on length of
      productive life of cows.

PMID- 7738249
TI  - Intake limitations, feeding behavior, and rumen function of cows challenged with
      rumen fill from dietary fiber or inert bulk.
AB  - Twelve multiparous, rumen-cannulated cows (17 DIM) were fed 25 or 35% NDF diets
      without or with added rumen-inert bulk as water-filled plastic containers (500 ml
      each) within three 4 x 4 Latin squares (21-d periods). Added bulk equaled 25% of
      pretrial rumen volume for each cow. Objectives were to challenge cows with rumen
      fill in the form of dietary NDF and inert bulk to determine whether bulk affects
      intake similarly for diets of different NDF content or whether changes in
      behavior or rumen function allow cows to adapt to higher fill. Inert bulk had no
      effect on DMI for cows fed 25% NDF but decreased DMI for cows fed 35% NDF (18.7
      vs. 16.6 kg/d). Volume of rumen digesta plus inert bulk, 102 L, was similar for
      35% NDF treatments regardless of presence or absence inert bulk. Additional NDF
      or inert bulk increased the number of ruminating bouts per day, chewing time per
      unit of DMI or NDF intake, frequency of reticular contractions during rumination,
      and fractional passage rate of NDF from the rumen. Although these changes may
      help to alleviate fill, they were insufficient to maintain intake under
      conditions of high fill. Intake by cows receiving high fiber diets can be limited
      by reticulorumen capacity. Future study is required to determine the effect of
      rumen fiber digestion, fiber particle size, and animal characteristics on fill
      limited intake.

PMID- 7738250
TI  - Digestibility by dairy cows of monosaccharide components in diets containing
      wheat or ryegrass silages.
AB  - Digestibility by dairy cows of monosaccharide constituents in rations based on
      wheat or ryegrass silage as the sole roughage component was examined in this
      study. Six cows in early lactation were divided into two groups with similar
      performance data at the onset of the experiment and fed for ad libitum intake for
      two 28-d periods in a change-over design. Cows were fed a TMR of concentrate plus
      either wheat or ryegrass silage, contributing 19% of silage NDF in the TMR.
      Digestibilities of ration DM and total carbohydrate were 3.3 and 3.1 percentage
      units higher, respectively, for ryegrass than for the wheat silage. The
      digestibility of ration NDF was 64.1% in ryegrass silage and 49.6% in wheat
      silage. The trend was similar for digestibilities of NDF monosaccharide
      components. Ration NDF carbohydrate digestibility was 74.8% for ryegrass silage
      versus 59.7% for wheat silage. For both TMR, the digestibility of NDF xylose was
      lower than that for NDF glucose and arabinose. Based on carbohydrate
      digestibility, ryegrass silage can be considered to be a successful roughage
      alternative for wheat silage in TMR for lactating cows.

PMID- 7738251
TI  - Effect of corn silage supplementation on intake and milk production in cows
      grazing grass pasture.
AB  - The objective was to determine the effects on milk production and DMI of 2.3 kg/d
      of corn silage DM fed to lactating cows grazing grass pasture and fed
      supplemental grain. Thirty Holstein cows, averaging 32 kg of milk at the start of
      the trial, intensively grazed grass pasture for 8 wk. One-half of the cows
      received 2.3 kg/d of corn silage DM in two equal feedings, and one-half of the
      cows were used as controls (no corn silage). All cows were fed grain at 1 kg of
      grain DM/4 kg of milk. Corn silage had no effect on milk production or milk
      composition. Cows fed corn silage did not have improved BW gain or body condition
      score. Each unit of corn silage consumed replaced 1.2 units of pasture, but total
      DMI was not different because of supplementation with corn silage. Blood urea N
      concentrations were lower for cows fed corn silage. Supplementation of high
      producing Holsteins grazing grass pastures with 2.3 kg/d of corn silage DM had no
      effect on milk production, milk composition, or total DMI.

PMID- 7738253
TI  - Effect of prepartum and postpartum dietary energy on growth and lactation of
      primiparous cows.
AB  - Sixty-seven Holstein replacement heifers (19 mo) were fed a standard (59.7% TDN)
      or a high energy (69.3% TDN) diet until parturition. After parturition,
      primiparous cows were fed either 0 or 2.8% supplemental tallow for 150 d in a 2 x
      2 factorial arrangement with prepartum treatments. High energy prepartum
      increased BW (693.5 vs. 663.7 kg) and body condition scores (3.72 vs. 3.55) at
      calving. Increased energy density of the diet prepartum did not affect milk yield
      or composition. Supplemental dietary fat postpartum increased milk yield
      approximately 1.5 kg/d, but the response was not observed until 7 wk postpartum.
      Heifers fed the standard diet prepartum and no supplemental fat postpartum had
      higher DMI than other treatments. Heifers fed high energy prepartum and
      supplemental fat postpartum lost the greatest BW and body condition from 1 to 5
      wk postpartum. Heifers fed high energy diets prepartum had higher concentrations
      of blood NEFA, BHBA, and liver triglycerides. Increases in BW and body condition
      scores at calving above approximately 660 kg and 3.5, respectively, do not
      enhance lactation performance. When 2.8% supplemental fat was fed to primiparous
      cows, milk yield improved approximately 1.5 kg/d after wk 7 of lactation.

PMID- 7738252
TI  - In situ ruminal disappearance of essential amino acids in protein feedstuffs.
AB  - Four protein sources were incubated in situ to estimate AA disappearance. Bags
      containing either soybean meal, corn gluten meal, herring meal, or meat meal were
      washed in water or suspended in the rumen of two Holstein cows for 8, 12, 16, 24,
      48, 72, and 120 h. Cytosine, a bacterial marker for microbial contamination, was
      used to correct the essential AA profile for microbial contribution to determine
      the residual essential AA composition of the protein sources after incubation.
      Ruminal disappearance of individual essential AA was different among feedstuffs.
      Relative to original feed protein, soybean meal and corn gluten meal decreased
      the concentration of specific essential AA in the RUP. Concentration of all
      essential AA, except Arg and His, increased in undegraded meat meal protein. The
      difference between original and residual AA concentrations in herring meal
      approached statistical significance. Use of the original AA profile of the feed
      protein to predict essential AA available for absorption is not accurate because
      accuracy differs with sources.

PMID- 7738254
TI  - Effect of whole cottonseeds and calcium salts of long-chain fatty acids on
      performance of lactating dairy cows.
AB  - Holstein cows were assigned to diets containing no supplemental fat, supplemental
      fat from whole cottonseed, or supplemental fat from whole cottonseed plus Ca
      salts of fatty acids (Megalac). The TMR contained 46% forage and 54% concentrate
      or mixtures of concentrate and whole cottonseed on a DM basis and were fed from
      wk 3 through 44 of lactation. The mean fat content of the three diets was 3.0,
      4.7, and 6.4% of DM for control, whole cottonseed, and whole cottonseed plus Ca
      salts of fatty acids, respectively. Supplemental fat increased NEL intake,
      percentage of milk fat, milk fat production, and rate of recovery of BW and body
      condition. Supplemental fat decreased milk protein production in early lactation,
      but not in late lactation. Addition of supplemental fat had no significant effect
      on ruminal concentration of VFA, NH3 N, or in situ digestibility of fiber. The
      proportion of unsaturated fatty acids in milk fat was increased with supplemental
      whole cottonseed or whole cottonseed plus Ca salts of fatty acids. During the
      first 3 mo of lactation, the proportion increased of fatty acids C14 or less,
      C16, and C18:2. Proportion of fatty acids C16:1 and C18:1 correspondingly
      decreased. The change in composition of milk fatty acids during early lactation
      is consistent with the use of body fat for milk synthesis.

PMID- 7738256
TI  - Genetic parameters for milk yield, survival, workability, and type traits for
      Australian dairy cattle.
AB  - Genetic parameters, such as heritabilities and genetic correlations were
      estimated for milk yield, survival, workability, and type traits for Australian
      Holstein-Friesian and Jersey cattle. All analyses were performed using
      multivariate REML with a sire model. Heritabilities for lactation yield traits
      were moderate, ranging from .20 to .28, and heritabilities for mean test day
      deviations were approximately .40 higher. Heritabilities for survival
      (probability of surviving to the next lactation) were low, ranging from .02 to
      .08. Genetic correlations between survival scores were high, ranging from .37 to
      .98, in particular between adjacent survival scores (on average .91 and .97 for
      Holstein-Friesians and Jerseys). Heritabilities for stayabilities were larger,
      ranging from .03 to .22. On average, genetic correlations between stayabilities
      were very high, ranging from .66 to .99. For milking speed, temperament, and
      likeability, heritability estimates ranged from .18 (for likeability in Holstein
      Friesians) to .29 (for milking speed in Jerseys). Undesirable scores for milking
      speed and temperament had negative genetic correlations with stayabilities
      (correlations approximately -.20). Heritabilities for type traits were all
      moderate (.11 to .42), and genetic correlations among type traits and between
      type traits and production traits were large. Phenotypic correlations between
      type traits and stayabilities were low. Generally, genetic correlations between
      type traits and stayabilities were low although the standard errors of those
      estimates were large.

PMID- 7738255
TI  - Hydrolyzed soy protein isolate sustains high nutritional performance in veal
      calves.
AB  - Milk replacers containing skim milk powder or a mixture of whey and soy protein
      provided by a hydrolyzed soy protein isolate or a heated soybean flour were fed
      to 1-mo-old calves for 101 d. The isolate and the flour provided 56 and 72% of
      dietary proteins, respectively. Digestibility of feed constituents was measured
      between 9 to 14 d and 65 to 70 d of treatment. Digestive function was evaluated
      by measurement of ruminal pH, plasma kinetics of triglyceride and glucose
      concentrations, and xylose absorption. Antibody production was also recorded.
      Growth and carcass characteristics were satisfactory for the control diet and the
      diet based on soy isolate, partly because of high apparent digestibility of
      protein and lack of antibody synthesis in response to soy isolate. In contrast,
      protein from soybean flour was poorly digested and highly immunogenic. Ruminal pH
      at 2.5 h after the meal was unaffected by dietary treatments. Postprandial
      changes in concentrations of triglycerides and glucose in plasma suggested a lack
      of abomasal clotting with both diets based on soy. Xylose concentration in plasma
      was only slightly affected by dietary treatment and calf age. Hydrolyzed soy
      protein is suitable for veal calves and can account for at least half of protein
      intake.

PMID- 7738257
TI  - Multiplicative factors for estimation of daily milk and component yields from
      single morning or afternoon tests.
AB  - Prediction of daily yield from single a.m. or p.m. milkings requires factors that
      are the reciprocal of the proportion of total yield expected from single milkings
      given the milking interval. Further adjustments to estimated milk yield account
      for DIM. Factors used by the Cornell Dairy Records Processing Lab were estimated
      from data collected from August 1983 to November 1984. These factors appear to be
      biased. Inconsistent estimates of daily yield were observed monthly. New factors
      were developed using recent data. Factors from a.m. milkings for milk and protein
      yield were smaller than those currently in use. The reverse was true for fat
      yield. Covariants for DIM were larger than those currently used. Differences were
      observed when factors using data with known and assumed milking intervals were
      compared. Factors for a.m. milkings with known intervals were smaller than those
      from p.m. milkings with the same known intervals. Use of covariants for DIM were
      compared with covariants for single milk yield. The latter explained more
      variation in yield. Factors were tested on independent data. New factors with
      covariants for single milk yield performed best for estimation of total daily
      yield.

PMID- 7738258
TI  - Heat-induced interactions between the proteins of milk fat globule membrane and
      skim milk.
AB  - Milk fat globule membrane proteins in washed cream were analyzed using
      preparative isoelectric focusing followed by SDS-PAGE. Five major protein bands
      of milk fat globule membrane were observed with apparent molecular mass of 150,
      67, 62.5, 51, and 49 kDa. The protein of band 5 (49 kDa) was well separated from
      the protein of band 4 (51 kDa). Heat-induced effects (72 and 87 degrees C for
      2.5, 5, 10, 20, 30, and 60 min) on whole milk proteins were also investigated
      under nonreducing and reducing conditions to study disulfide interactions between
      serum proteins and those in the fat membrane. beta-Lactoglobulin and other milk
      serum proteins interacted readily with milk fat globule membrane and membrane
      proteins at 87 degrees C, but only slightly at 72 degrees C. However, the
      interactions between serum proteins and fat globule membrane proteins cannot be
      explained solely by disulfide linkage formation. Some membrane proteins,
      especially the 49-kDa protein (band 5), underwent drastic changes after heat
      treatment. Further characterization of the 49-kDa protein demonstrated that it
      binds concanavalin A; AA composition and N-terminal sequence of the protein were
      determined and compared with those reported in the literature.

PMID- 7738259
TI  - Iron removal from milk and other nutrient media with a chelating resin.
AB  - A water-insoluble iron(III)-chelating resin was used to study iron removal from
      milk and other nutrient media. Seventy to 85% of the iron could be removed from
      wine and beer with the resin, which was a crosslinked copolymer of 1-(beta
      acrylamidoethyl)-3-hydroxy-2-methyl-4(1H)- pyridinone and N,N-dimethylacrylamide.
      Iron removal from milk was dependent on the pH of milk and on the concentration
      of soluble chelators added. Under the same conditions as used for the removal of
      iron from wine and beer, only 11 to 19% of the iron could be removed from milk.
      However, in combination with water-soluble chelators, the resin removed 60 to 75%
      of the iron from the milk. Preliminary results showed that the growth of spores
      of Clostridium tyrobutyricum in the treated milk was reduced. Moreover, addition
      of the resin and sodium bicarbonate to the milk completely inhibited the growth
      of the spores.

PMID- 7738260
TI  - Administration of 13-cis-retinoic acid to dairy cattle. 1. Plasma retinoid
      concentrations and lymphocyte blastogenesis.
AB  - Effects of administration of 13-cis-retinoic acid on concentrations in plasma of
      retinoic acid isomers, retinol, and beta-carotene and on in vitro mitogen
      stimulated lymphocyte blastogenesis of peripheral blood mononuclear leukocytes
      were evaluated in Holstein cattle. Treatments consisted of i.m. injections of 0
      (vehicle only), 100, 200, or 400 mg of 13-cis-retinoic acid in dimethylsulfoxide
      for 7 d. Concentrations of 13-cis- and all-trans-retinoic acids in plasma and in
      mononuclear leukocytes were elevated in a dose-dependent manner by administration
      of 13-cis-retinoic acid. Treatment with 13-cis-retinoic acid, however, had no
      effect on concentrations of retinol and beta-carotene in plasma. In vitro DNA
      synthesis in unstimulated and mitogen-stimulated mononuclear leukocyte cultures
      was unaffected by in vivo administration of 13-cis-retinoic acid. In contrast, in
      vitro supplementation of unstimulated and mitogen-stimulated mononuclear
      leukocyte cultures with 13-cis-retinoic acid inhibited DNA synthesis relative to
      unsupplemented cultures. In conclusion, elevated plasma and intracellular
      concentrations of 13-cis- and all-trans-retinoic acids produced by repeated i.m.
      administrations of 13-cis-retinoic acid did not affect peripheral blood
      mononuclear leukocyte function, as measured by the in vitro blastogenic response
      of peripheral blood lymphocytes.

PMID- 7738261
TI  - Administration of 13-cis-retinoic acid to dairy cattle. 2. Phenotype of blood
      leukocytes and production of immunoglobulin.
AB  - Eight Holstein dairy cattle were assigned randomly to treatments in three
      replicate experiments evaluating the effects of 13-cis-retinoic acid on
      mononuclear leukocyte function. Treatments were i.m. injections of 0 (vehicle
      only), 100, 200, or 400 mg/d of 13-cis-retinoic acid in dimethylsulfoxide for 7
      consecutive d. Peripheral blood was collected before treatment and periodically
      for 18 d after initiation of treatments. Parameters measured were IgM production
      in vitro by blood lymphocytes, serum Ig concentrations, and the phenotype of
      peripheral blood mononuclear leukocytes. Administration of 13-cis-retinoic acid
      had no effect on in vitro Ig production induced by pokeweed mitogen; however,
      supplementation of the same cultures with 13-cis-retinoic acid enhanced
      production of polyclonal IgM. Serum Ig concentrations and total numbers of
      peripheral blood leukocytes and numbers within mononuclear leukocyte subsets were
      unaffected by treatment with 13-cis-retinoic acid. Experimentally induced
      elevations in the concentrations of serum and intracellular retinoic acids did
      not affect mononuclear leukocyte function in vivo.

PMID- 7738262
TI  - Comparison of bovine sperm capacitation systems for ability of sperm to penetrate
      zona-free hamster oocytes and bovine oocytes matured in vitro.
AB  - Sperm from the same ejaculate were capacitated in calcium-free Tyrode's, modified
      Tyrode's with bovine follicular fluid or heparin, and TEST-yolk. Capacitated
      sperm were coincubated with zona-free hamster oocytes at 37 degrees C for 3 h or
      with bovine cumulus-enclosed oocytes matured in vitro for 8 h at 37 or 39 degrees
      C. Bovine oocytes were transferred to fertilization medium and incubated for 72 h
      at 37 or 39 degrees C. Penetration of zona-free hamster oocytes was highest in
      calcium-free Tyrode's (53.7%), followed by Tyrode's with follicular fluid
      (50.6%), TEST-yolk (48.6%), and Tyrode's with heparin (34.2%). Penetration of
      bovine cumulus-enclosed oocytes matured in vitro at 37 degrees C was highest with
      heparin (48.1%), followed by TEST-yolk (35.0%), calcium-free Tyrode's (32.5%),
      and follicular fluid (26.4%). Sperm capacitation with heparin, assayed by
      penetration of bovine oocytes at 39 degrees C, was better at 39 degrees C (77.1%)
      than at 37 degrees C (46.1%). However, penetration rates in calcium-free Tyrode's
      and TEST-yolk were higher at 37 degrees C. The capacitation system with heparin
      at 39 degrees C and bovine oocytes was best followed by the systems using TEST
      yolk and calcium-free Tyrode's at 37 degrees C.

PMID- 7738263
TI  - Comparison of various bovine sperm capacitation systems for their ability to
      alter the net negative surface charge of spermatozoa.
AB  - Semen was divided into five aliquots and capacitated for 4 or 6 h in calcium-free
      Tyrode's (37 degrees C), modified Tyrode's bovine follicular fluid (39 degrees
      C), modified Tyrode's heparin (39 degrees C), and TEST-yolk buffer (4 degrees C)
      or incubated in BSA-saline (39 degrees C). Sperm before and after capacitation
      were electrophoresed at 100 V of constant current for 3 and 6 min. Samples were
      collected, sperm were counted, and percentages of sperm migrating toward the
      anode at 0 h and 4 or 6 h were calculated. At 0 h, 61 to 80% of the sperm
      migrated with a net negative charge. After 4 or 6 h, the percentage of sperm
      migrating toward the anode significantly decreased in all capacitation media but
      not in the control. The percentage of sperm migrating toward anode was lowest in
      calcium-free Tyrode's (22.1%) followed by TEST (28.4%), Tyrode's follicular fluid
      (29.5%), and Tyrode's heparin (42.5%); these values were less than those for the
      control (56.0%). The movement of live sperm without the influence of current or
      freeze-killed sperm under the influence of electrical current (control trials)
      was negligible. Capacitation reduced the net negative surface charge of sperm,
      the magnitude of which depended on capacitation system. Net negative charge of
      sperm was inversely associated with efficiency in penetration of zona-free
      hamster oocytes.

PMID- 7738264
TI  - Effect of various capacitation systems on bovine sperm motion characteristics,
      acrosome integrity, and induction of hyperactivation.
AB  - Sperm from the same ejaculate were capacitated in TEST-yolk, calcium-free
      Tyrode's, modified Tyrode's containing follicular fluid or heparin, and analyzed
      at 0, 4, 8, and 12 h for motility characteristics and acrosomal integrity.
      Percentage of motility, progressive motility, progressive velocity, path
      velocity, curvilinear velocity, linearity, and amplitude of lateral head
      displacement differed with media and decreased with time. Calcium-free Tyrode's
      ranked first in maintaining most motility parameters. However, TEST-yolk sperm
      ranked first for lateral head displacement but last for linearity at each time.
      Acrosome-reacted sperm increased over time but were not different between TEST
      yolk, calcium-free Tyrode's, and heparin at 4 h. The TEST-yolk sperm at 4 h had
      about twice the hyperactivation (62.3%) of the other sperm capacitation media.
      Capacitation of bovine sperm was not associated with a specific change in any
      measured motility parameter. Differences among the efficacies of capacitation
      systems were unrelated to parameters of sperm motion, hyperactivation, or
      acrosomal integrity.

PMID- 7738265
TI  - Effects of several tea components on acid resistance of human tooth enamel.
AB  - OBJECTIVES: The effects of tea components on the acid resistance of human tooth
      enamel were investigated by an in vitro experiment. A further study focused on
      the action of tannin, the main component of tea, in combination with fluoride.
      RESULTS: Some components such as tannin, catechin, caffeine and tocopherol were
      demonstrated to be effective for increasing acid resistance, and their effects
      increased dramatically when they were used in combination with fluoride. A mixed
      solution of tannic acid and fluoride showed the highest inhibitory effect (98%)
      on calcium release to an acid solution. Tannin in combination with fluoride
      showed obvious inhibition of the formation of artificial enamel lesions in
      comparison with APF as determined by electron probe microanalysis, polarized
      light microscopy and Vickers microhardness measurement. CONCLUSIONS: These
      results demonstrate that besides the fluoride, the organic components of tea also
      possess the property of increasing the acid resistance of tooth enamel. They also
      suggest that the organic components appear to play a primary role in their
      actions rather than fluoride.

PMID- 7738266
TI  - Wear patterns in two amalgams and three posterior composites after 5 years'
      clinical service.
AB  - OBJECTIVES: The purpose of this research was to evaluate the wear patterns of
      three posterior composites (Clearfil Posterior. Occlusin and P-30) and two
      amalgams (New True Dentalloy, Solila Nova) after 5 years' clinical service.
      METHODS: Marginal wear was measured using the stepwedge technique which
      determines the maximal marginal wear by any one cusp together with the mean
      marginal value. The overall maximum depth of wear, occurring at any site on the
      occlusal surface, was determined using an impression technique with epoxy models.
      RESULTS: The mean values (+/- standard deviations) for the overall maximum wear
      were: New True Dentalloy, 203 +/- 98 microns; Solila Nova, 200 +/- 96 microns;
      Clearfil Posterior, 252 +/- 141 microns; Occlusin, 324 +/- 189 microns; P-30, 380
      +/- 273 microns. These values were significantly different (ANOVA F = 2.86 P =
      0.05). There was no correlation between the marginal scores and the overall
      maximum depth of wear (P > 0.05). There was no correlation between the marginal
      scores and the overall maximum depth of wear (P > 0.05). With some restorations
      the maximum wear occurred at the margins, marginal ridges or cavity extensions
      rather than sites of occlusal contact. CONCLUSIONS: After 5 years' service the
      overall wear of three posterior composites exceeded that of two amalgams;
      however, for a number of restorations the difference was not significant.
      Marginal wear values cannot be used to predict the overall maximal depth of wear.

PMID- 7738267
TI  - Effectiveness of ethylene oxide for sterilization of dental handpieces.
AB  - Ethylene oxide gas has been utilized as an alternative method for sterilization
      of dental handpieces, as it is less corrosive than steam. However, its
      effectiveness for sterilization of the internal components of dental handpieces
      has not been established. The objective of this study was to compare the
      effectiveness of ethylene oxide and steam for sterilization of dental handpieces.
      Unused handpieces and handpieces which had been exposed to clinical dental
      procedures ('clinical') were contaminated with Streptococcus mutans, exposed to
      steam or ethylene oxide, and flushed with sterile saline. Washings were plated on
      mitis-salivarius agar, and colonies identified and counted. No viable colonies
      could be established from washings from 'clinical' or 'unused' handpieces exposed
      to steam. However, viable colonies could be established from 'clinical'
      handpieces exposed to ethylene oxide. This data suggests that a substance
      entrapped within 'clinical' handpieces (possibly the biofilm) may protect
      bacteria from ethylene oxide gas, preventing adequate sterilization.

PMID- 7738268
TI  - Water content in experimental dentine primers to minimize the contraction gap
      width of a light-cured resin composite.
AB  - OBJECTIVES: The effect of water content in experimental dentine primers
      consisting of an aqueous solution of either glyceryl methacrylate (GM) or
      hydroxyethyl methacrylate (HEMA), and in experimental self-etching dentine
      primers composed of methacryloxyethyl hydrogen phenyl phosphate (Phenyl-P), was
      evaluated by measuring the wall-to-wall polymerization contraction gap width of a
      commercial light-activated resin composite filled in a cylindrical dentine cavity
      prepared in an extracted human molar. METHODS: A commercial light-cured dentine
      bonding agent was applied to the cavity after cleaning with EDTA and priming with
      either GM or HEMA, or after self-etching priming by Phenyl-P diluted in either GM
      or HEMA solution. RESULTS: In the GM and HEMA solutions, the gap width was
      minimized when the water content was 65 wt% even though gap formation could not
      be prevented by HEMA solution. With the self-etching dentine primers, gaps could
      not be observed under the light microscope with 16 wt% Phenyl-P diluted in 35 wt%
      GM or HEMA or with 20 wt% Phenyl-P diluted in 20 wt% GM or HEMA. CONCLUSION: The
      water content in both the experimental dentine primers and the self-etching
      dentine primers which yielded the minimum contraction gap width for the resin
      composite in the dentine cavity was approximately 60 wt%.

PMID- 7738269
TI  - A new temporary soft lining material.
AB  - The viscoelastic properties of a new light-activated temporary denture soft
      lining material have been monitored in vitro using a force/distance probe. Its
      baseline behaviour was characteristic of an elastic material and its compliance
      considerably less than that of both a short-term and a long-term soft lining
      material which were used as controls. Sample thickness had no appreciable effect
      on this compliance. These results suggest that the new product is likely to be
      perceived as being significantly harder by a patient. Twenty-four weeks'
      immersion in distilled water had no significant effect on either the compliance
      or elasticity of the test material and would suggest an improved durability when
      compared to other conventional short-term resilient denture lining materials,
      albeit at the expense of compliance.

PMID- 7738270
TI  - Dental materials: 1993 literature review.

PMID- 7738271
TI  - Dietary staining in vitro by mouthrinses as a comparative measure of antiseptic
      activity and predictor of staining in vivo.
AB  - Extrinsic staining of teeth is a side-effect of some antiseptic mouthrinses.
      However, few of the many rinse products available to the general public have been
      investigated for their propensity to cause staining. Dietary factors play an
      aetiological role in staining and have been used in vitro to study and compare
      the activity of rinses. The aim of this study was to assess rinse products for
      staining in vitro and, through the staining reaction, to compare the activity of
      products containing the same ingredients. Perspex blocks, with or without saliva
      pretreatment, were soaked in rinses for 2 min, washed and placed in a standard
      tea solution for 60 min and then the optical density (OD) read on a
      spectrophotometer. The cycle was repeated 10 times for saliva and 17 times for no
      saliva specimens or until the maximum OD was exceeded. A series of three separate
      experiments was performed by this method. The maximum OD was not exceeded by any
      product before seven passages and therefore data were compared at six passages.
      For most products OD increased with saliva pretreatment. Some cetylpyridinium
      chloride (CPC) rinses stained comparably to a chlorhexidine rinse. CPC rinses,
      most of which contained the same concentration of the antiseptic, varied
      considerably in their propensity to induce staining and one was little different
      to water controls. A 0.1% chlorhexidine rinse stained slightly more than a 0.2%.
      A phenolic/essential oil product produced some staining but zinc, triclosan and
      other essential oil rinses did not stain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738272
TI  - Staphylococcus aureus isolated from nostril anteriors and subungual spaces of the
      hand: comparative study of medical staff, patients, and normal controls.
AB  - An epidemiologic investigation of methicillin-resistant Staphylococcus aureus
      (MRSA) and Staphylococcus aureus (S. aureus) colonization was conducted at Kansai
      Medical University Hospital between 1990 and 1991. The incidence of nasal and
      subungual positivity for S. aureus was examined in a total of 156 subjects
      including inpatients, physicians, and nurses at a ward for dermatology, plastic
      surgery, and emergency patients, outpatients with atopic dermatitis and other
      skin diseases, and normal controls. Inpatients were most heavily colonized with
      MRSA (40.8%), but S. aureus colonization was most frequent in outpatients with
      atopic dermatitis (95.5%). Not only nostrils, which have been much discussed as a
      reservoir of S. aureus, but also subungual spaces seemed to be havens of S.
      aureus. Twelve out of 22 atopic dermatitis patients were positive for S. aureus
      on skin regions, and coagulase and phage testing showed a correlation between the
      nasal and skin-colonizing S. aureus. Coagulase type II and phase type NT (not
      typable) were the predominant types of S. aureus, including MRSA.

PMID- 7738274
TI  - Clinical analysis of recurrent hypergammaglobulinemic purpura associated with
      Sjogren syndrome.
AB  - Recurrent purpuric lesions are occasionally seen in patients with Sjogren
      syndrome. Hypergammaglobulinemia is one of the underlying precipitating factors
      of this condition. Clinical and histopathological analyses were performed on 5
      cases of hypergammaglobulinemic purpura associated with Sjogren's syndrome, and
      the effects of immunomodulatory therapy were evaluated with regards to these
      conditions. Three out of 5 cases were successfully treated with oral gold
      compound (Auranofin) and one case with a low dose of cyclophosphamide. Episodic
      purpura subsided two months after initiation of therapy with improved serum IgG
      levels. Salivary flow and serum amylase levels also improved in some cases.
      Immunomodulatory therapy may be useful in managing recurrent purpura based on
      hypergammaglobulinemia associated with Sjogren syndrome.

PMID- 7738273
TI  - Gamma-interferon therapy for severe cases of atopic dermatitis of the adult type.
AB  - Recombinant gamma interferon (IFN-gamma) was employed to treat adult-type atopic
      dermatitis. Eight cases received subcutaneous injections of 500,000 JRU of IFN
      gamma for 8 weeks. They responded relatively well to this treatment; however, the
      overall response to the treatment was not significantly better than that to
      conventional therapy in the control group. There was no significant suppression
      of itch or erythema. Swelling was reduced at the 8th week in the treatment group.
      Frequency of flushing attacks on the face was reduced and disappeared within four
      weeks in 6 of these patients; however, a similar reduction of frequency was
      observed in the control group. Papular and lichenified lesions on the trunk and
      extremities responded significantly to the treatment later than 5 weeks after its
      initiation. Serum IgE level was not affected by the treatment. Seven had the same
      level of serum IgE before and after the treatment. The serum cytokine level in
      the treated patients was also unaltered. Therefore, although IFN-gamma treatment
      has some benefit in the treatment of severe cases of atopic dermatitis, it should
      be applied to limited cases because of its high cost.

PMID- 7738275
TI  - Mortality of neurofibromatosis in Japan, 1968-1992.
AB  - The death rate from neurofibromatosis (NF) was analyzed using Japanese vital
      statistics for the period 1968-1992. NF death rates for females decreased
      significantly year by year, but there was no significant change for males.
      Overall NF death rates were 0.25 per million population for males and 0.19 for
      females. The age-specific NF death rate increased with age during that period.
      The overall mean age at death from NF was 43 years for both sexes. There were no
      geographical variations in the NF death rate during the period 1977-1992.

PMID- 7738276
TI  - The effects of non-interval PUVA therapy on the plaque stage of mycosis
      fungoides.
AB  - The effectiveness of non-interval topical PUVA treatment was studied in four
      patients with mycosis fungoides at the plaque stage. Five regions of each patient
      were exposed to UVA immediately, 30 minutes, 60 minutes, 90 minutes, and 120
      minutes, after topical application of 8-methoxypsoralen, respectively. The
      effects of these treatments were evaluated by clinical appearance and
      histological findings after the 20th treatment. All five regions were more
      improved clinically and histologically than the control region, which was not
      given PUVA therapy. There were no clear differences clinically among these five
      regions. Biopsy specimens from each region revealed the disappearance of
      epidermotropism and a marked decrease in atypical mononuclear cell infiltrations
      in the dermis. From these data, we concluded that there were no clear differences
      between these five treatments clinically or histologically and that non-interval
      PUVA therapy is useful for the early stages of mycosis fungoides. To our
      knowledge, this is the first report of non-interval PUVA therapy for mycosis
      fungoides.

PMID- 7738277
TI  - Pemphigoid nodularis: a case with 230 kDa hemidesmosomes antigen associated with
      bullous pemphigoid antigen.
AB  - We report a 73-year-old woman with typical clinical, histological and
      immunofluorescence features of pemphigoid nodularis. Direct immunofluorescence
      studies of prurigo nodularis-like lesions and peribullous skin showed the linear
      deposition of IgG and C3 at the basement membrane zone. Circulating IgG against
      the basement membrane was also detected by indirect immunofluorescence. The serum
      from the patient was shown to contain the autoantibody against 230 kDa
      hemidesmosomal antigen associated with bullous pemphigoid antigen.

PMID- 7738278
TI  - Systemic plasmacytosis: a case which improved with melphalan.
AB  - Plasmacytosis, a distinctive proliferative disorder of plasma cells, is
      characterized by peculiar multiple skin eruptions, lymphadenopathy and polyclonal
      hypergammaglobulinemia. To date there has been no report of such cases showing
      remarkable responses to therapeutic agents. We herein report a case of
      plasmacytosis which developed in a 52-year-old Korean man and showed remarkable
      improvement with melphalan.

PMID- 7738279
TI  - Verrucous plaque: unique morphological expression of post-kala-azar dermal
      Leishmaniasis (PKDL).
AB  - Relatively unusual verrucous plaque as well as other expressions of P.K.D.L. are
      reported in a 46-year-old male. The diagnosis was confirmed by the documentation
      of Leishman-Donovan bodies in the tissue smears as well as in the cytoplasm of
      the histiocytes in the tissue section.

PMID- 7738280
TI  - Lymphoepithelioma-like carcinoma originating on the eyelid.
AB  - An 89-year-old woman presented a rapidly growing red nodule of 5 years' duration
      on her left eyelid. Histologically, the entire dermis was occupied by multiple
      lobules of atypical tumor cell nests surrounded by inflammatory cells and fibrous
      stroma. The tumor cell nests were connected with the overlying epidermis and
      extended into the subcutaneous fat and muscles. There were no tendencies towards
      squamous or glandular differentiation of the tumor cells. Immunohistochemistry
      showed the tumor cells to be positive for keratin/cytokeratin and epithelial
      membrane antigen, but negative for neuron specific enolase and vasoactive
      intestinal polypeptide. S-100 protein-positive Langerhans cells were also found
      within the tumor nests. There was no apparent evidence of a primary lesion
      elsewhere.

PMID- 7738281
TI  - A case of Bowen's disease with tissue eosinophilia.
AB  - An 85-year-old Japanese man with Bowen's disease on the left inguinal area is
      reported. Most of the inflammatory cells adjacent to the tumor were eosinophils.
      Tissue eosinophilia spontaneously improved after biopsy.

PMID- 7738282
TI  - Bilateral basal cell carcinoma of the breasts in a woman.
AB  - Basal cell carcinomas (BCC) on covered sites of the body are rare (1). A case of
      a young woman with superficial basal cell carcinoma of both breasts is described.
      No history of sun bathing, X-ray, or arsenical exposure was reported. Simple
      excision of both lesions was performed without recurrence.

PMID- 7738283
TI  - Heart rate variability in infants, children and young adults.
AB  - Heart rate variability was studied in normal subjects age 1 month-24 years while
      awake and in active and quiet sleep using 24 h continuous recordings of the ECG.
      Variability was quantified by spectral analysis for the two frequency bands: low
      frequency (LF) 0.03-0.15 Hz, high frequency (HF) 0.15-0.6 Hz. Heart rate
      variability showed an age dependence, being in general an increase in LF, HF and
      total power from 0-6 years, followed by a decrease to 24 years. The infant group
      showed some exceptions to this trend. Developmental changes of parasympathetic
      and sympathetic mediation of heart rate are postulated as important determinants
      of age dependence of heart rate variability.

PMID- 7738284
TI  - Lacrimation and cutaneous vasodilatation in the face induced by painful
      stimulation of the nasal ala and upper lip.
AB  - The effect of painful stimulation of the nasal ala and upper lip on lacrimation
      and cutaneous vascular responses in the forehead and cheeks was investigated in
      11 normal subjects. In addition, the mechanism of the response was studied in 10
      patients with a lesion compromising parasympathetic activity in the facial nerve.
      In normal subjects, pinching the nasal ala with forceps increased blood flow on
      the ipsilateral side of the forehead but not the cheek. Pinching the upper-lip
      induced ipsilateral vasodilation in the forehead in 3 of 11 subjects, but not in
      the cheek. Pinching either site increased corneal moisture proportional to the
      size of the vascular response in the forehead. A facial nerve lesion inhibited
      the ipsilateral component of the vascular response in the forehead. These
      findings suggest that pain within the distribution of the first or second
      divisions of the trigeminal nerve excites vasodilator and lacrimal reflexes in
      the facial nerve. The increase in cutaneous flow during this trigeminal
      parasympathetic reflex appears to be limited to the forehead.

PMID- 7738285
TI  - The development of normal and peripherally deprived sympathetic neurons in the
      chick.
AB  - Sympathetic neuron numbers in four brachial paravertebral ganglia (segments 13
      16) were quantified during normal development and following wing bud removal. In
      ganglia with an intact peripheral field, different developmental profiles were
      observed. In particular, a period of increasing neuron numbers was seen in some,
      but not all ganglia from embryonic day 10. Similarly, a period of declining
      neuron numbers was present only in two ganglia, and this occurred at a time when
      sympathetic nerve fibres were detectable in the wing. Peak pyknotic activity
      occurred well before nerve fibres entered the wing. Thus, the bulk of the cell
      death is unrelated to peripheral innervation. Wing bud removal at embryonic day 3
      reduced neuron number by as much as 69% at embryonic day 20 compared to the
      number in the corresponding ganglia on the intact side. The most obvious effect
      was the failure to generate the full complement of neurons. This could be
      explained by a shift in pyknotic activity to a period of 1-2 days earlier than
      seen on the intact side. We therefore conclude that the developing wing
      influences the size of the sympathetic population both before and during the
      period of peripheral innervation.

PMID- 7738286
TI  - Projections of stellate ganglion sympathetic neutrons in cats.
AB  - Retrograde axonal transport of horseradish peroxidase (HRP) was used in this
      study to localize neurons in the cat stellate ganglion. The enzyme was applied to
      different nerves originating from the ganglion. Regardless of the site of HRP
      application labeled neurons in the stellate ganglion were located in the zone
      adjacent to the emergence from the ganglion of the nerves under study. However,
      neurons of a thoracic part of the sympathetic trunk were never labeled following
      exposure to HRP. The boundaries of the ganglion areas filled with labeled neurons
      after HRP application to different nerves did not completely overlap. The neurons
      labeled following HRP application to the vertebral nerve and the anastomosis of
      the stellate ganglion with the vagus nerve occupied the largest area. We conclude
      that neurons in the stellate ganglion of the cat are organized on a topical
      basis.

PMID- 7738287
TI  - The role of the autonomic nervous system in chemically-induced liver damage and
      repair--using the essential hypertensive animal model (SHR).
AB  - The effects of autonomic nervous system on liver damage induced by carbon
      tetrachloride (CCl4) and repair were investigated morphologically and
      biochemically in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats
      (WKY). After repetition of CCl4 treatment twice a week for 4 weeks, the SHR
      showed liver cirrhosis histologically. In WKY, however, only fibrosis was
      observed. Biochemically, the serum glutamate-pyruvate transaminase (GPT), liver
      lipid peroxidation (LPO) and superoxide dismutase (SOD) activities were measured.
      CCl4 increased the activities of GPT and LPO but decreased that of SOD in SHR
      more than in WKY. These findings indicate that liver damage induced by CCl4 was
      more severe in the sympathetic hyperactive SHR than in the normally active WKY.
      In induced cirrhotic liver of SHR and fibrotic liver of WKY, diffuse serotonin
      particles and numerous mast cells were observed in the fibrotic matrix, and some
      neovascular adrenergic fibers were found in these areas. These results indicate
      that the sympathetic nerve can exacerbate the liver damage, and both mast cells
      or serotonin particles and sympathetic nerve participate at some stages in the
      repair of liver damage.

PMID- 7738288
TI  - Cardiac rhythmic patterns in neuronal activity are related to the firing rate of
      the neurons: I. Brainstem reticular neurons of dogs.
AB  - Cardiac rhythmic discharge patterns (CRDP) of brainstem reticular neurons in
      anesthetized dogs were estimated by ECG-triggered post-event-time histograms
      (PETH). Modulations of the CRDP occur, whenever the firing levels of the neurons
      slowly change with periods longer than the cardiac cycle. Therefore, in the
      activity of one and the same neuron different types of CRDP can occur interlaced
      in time. 'Partial' PETHs calculated according to the discharge level of the
      neurons make these various CRDP obvious. On the other hand, the CRDP are not
      always so clear in the 'total' PETHs, taken from the continuous periods of
      activity. The meaning of these different CRDP for regulatory processes of the
      organism is discussed. We study the processing of the easily identifiable signal
      in neuron activity, i.e., cardiac rhythm, to illustrate how signal processing
      depends on the momentary activity level of the neurons which is influenced by
      other afferent signals and by inflows from central structures reaching the
      neurons.

PMID- 7738289
TI  - Cardiac rhythmic patterns in neuronal activity related to the firing rate of the
      neurons: II. Amygdala neurons of cats.
AB  - Neurons of the central and basal part of the amygdala complex were recorded in
      conscious, freely moving cats. These neurons have various cardiac rhythmic
      discharge patterns (CRDPs) which are estimated by post-event-time histograms
      (PETH). When the firing level of the neurons changed, the CRDPs were modulated.
      These modulations became obvious, when 'partial' PETHs of the neuronal activity
      were constructed according to the discharge level of the neurons. With changes of
      the neuronal discharge level different types of CRDPs were observed, interlaced
      in time during recordings of the same neuron. In 'total' PETHs, taken from the
      continuous periods of neuronal activity, cardiac rhythm was hidden or often was
      not so clearly visible as in 'partial' PETHs, taken at different discharge
      levels. As in case of neurons of the nucleus tractus solitarii (NTS) and for
      brainstem reticular neurons, amygdala neurons exhibited modulations of CRDPs as
      their activity level changed. The results indicate that the processing of
      activity patterns in these neurons depends on their activity level and functional
      organization, which is essentially dependent on afferent signals and influences
      from central structures reaching these neurons.

PMID- 7738290
TI  - [Treatment of refractory glaucoma with Nd:YAG laser cyclophotocoagulation].
AB  - We treated 54 eyes of 51 patients with refractory glaucoma by using contact
      transscleral Neodymium: YAG laser cyclophotocoagulation; 32 burns (7 watts during
      0.7 second) were applied to each eye by positionning the anterior edge of the
      probe at 0.5 to 1 mm from the limbus. The mean preoperative intraocular pressure
      (IOP) was 33.7 mmHg and the mean postoperative IOP was 25.6 mmHg with a follow-up
      of five months. There was a decrease of IOP in 72.3% of the cases. The
      postoperative IOP was controlled (IOP < 21 mmHg) in 41.3% of the treated eyes.
      Pain decreased in 6.7% of the cases that had no control of IOP and they could
      stop their medical treatment. During the follow-up period we observed neither
      early post operative hypertonia nor phtisis bulbi. Three eyes had scleral
      perforations. Laser treatment can be repeated if necessary in no controlled IOP
      cases. We had less complications with the laser treatment than with
      cyclocryoapplication. We described the advantages of the contact probe used.

PMID- 7738291
TI  - [Hypotensive action of 0.5% carteolol versus 0.1% timolol in patients with
      intraocular hypertension].
AB  - PURPOSE: The aim of the study was to compare 2 beta-blocker eye drops at a low
      concentration: 0.5% carteolol and 0.1% timolol. METHODS: The study was designed
      as a random-order, double-blinded comparison of 2 parallel treatment groups.
      Fifty patients with early primary open angle glaucoma or high intraocular
      pressure were included. The treatment lasted 4 weeks, on the basis of 1 drop
      twice daily. Diurnal I.O.P. curve was assessed with 4 measurements from 8.30 a.m.
      to 4.30 p.m. before and after treatment. The 8.30 a.m. measure of the final
      assessment of I.O.P. curve was established prior to morning medication. The mean
      values of the 4 measures were compared. RESULTS: Both treatments reduced IOP by a
      comparable amount: 4.25 +/- 1.2 mmHg (mean +/- SD) for carteolol and 4.69 +/- 1.9
      mmHg for timolol. The decrease of IOP was found at every time of assessment,
      without any significant difference between treatments. Both eye drops were very
      well tolerated. CONCLUSION: The results of this study show that the new beta
      blocker eye drop solution 0.5% carteolol is effective for initial management of
      high intraocular pressure.

PMID- 7738292
TI  - [Diabetic retinopathy. Interpretation of medical terms by patients].
AB  - This study evaluates how diabetic patients understand the meaning of 8 medical
      terms related to retinopathy. Divided into 4 groups, 142 persons, were questioned
      at the end of a consultation with their ophthalmologist. Groups 1, 2 and 3 were
      diabetic patients; 1, without retinopathy, 2, with pre-proliferative retinopathy,
      3, treated with laser. Group 4 included non-diabetic controls. The results show
      only one third of correct answers. Results illustrate a big diversity in
      understanding according to the terms which, nevertheless, were currently used by
      the doctors during their ophthalmological consultation. Sociodemographic
      variables did not have any effect on the understanding of terms dealing with
      diabetic retinopathy. We only observed a positive correlation between knowledge
      of patients and laser treatment. On analysing the contents of the patients'
      definitions, we discovered an important variety of different conceptions of the
      retinal disease. By not verifying patients' understanding of medical terms, both
      the physician and patient have no doubts as to their competence to understand
      them. This failure could have severe consequences not only at the level of
      prevention but also concerning the early treatment of diabetic retinopathy.

PMID- 7738293
TI  - [Treatment of refractory glaucoma with high density focused ultrasonics].
AB  - The efficacy of therapeutic ultrasound was retrospectively assessed in 456
      patients who presented with uncontrolled glaucoma refractory to maximal medical
      therapy and filtration surgery from April 1987 to January 1992. Treatment was
      performed under local anaesthesia in ambulatory outpatients. Therapeutic
      ultrasound induced local destruction of the ciliary epithelium and a thickening
      of the sclera. A 47% decrease in intraocular pressure (IOP) was obtained from the
      mean preoperative (33.8 mmHg) and the mean postoperative (18.2 mm Hg) values.
      After a 33-month mean follow-up, 65% of treated eyes had an IOP less than or egal
      to 20 mmHg. Therapeutic ultrasound was effective in most of the glaucomas,
      especially in open angle, closed angle, aphakic, pseudophakic and post-silicone
      oil glaucoma. The main complications were immediate ocular hypertension and
      corneoscleral alterations. Phtysis bulbi occurred in 5.7% of the eyes. The
      therapeutic interest of ultrasound were compared with those of the other
      cyclodestruction techniques.

PMID- 7738294
TI  - [Characteristics, stability and in vitro efficacy of cleaning products for
      contact lenses].
AB  - OBJECTIVE OF THE STUDY: We characterized some market products designed for
      cleaning contact lenses and we compared their properties to the main requirements
      of eye-washes. MATERIAL AND METHODS: We performed several physicochemical
      controls including pH determination, viscosity with a Baume apparatus and the
      decreasing of the freezing point following the method described by the French
      Pharmacopea. In addition, we carried out certain analytical controls, concerning
      three active principles (thiomersal, chlorhexidin digluconate, hydrogen
      peroxide), at the opening of the different package and after accelerated aging. A
      microbiological control was performed when opening the product and after a
      simulation of a 5-day aging. We finally determined the efficacy of the products
      on four bacterial strains for tests and of deproteinizing products on artificial
      dust. RESULTS: The pH values obtained ranged from 4.0 (oxygenated water
      solutions) to 7.8. The viscosity was close to a water solution one. Contents in
      active substances were usually similar to those stated on the package. At
      opening, the bacteriological quality was excellent. But, the multidose package
      were highly contaminated when used. Finally decontaminating efficacy against some
      germs was very good for the products tested. CONCLUSION: The results obtained
      show that the rincing products best answer the eye-wash criteria taken as
      references. Their main disadvantage is their contamination in the case of
      multidose packaging.

PMID- 7738295
TI  - [Ocular site of pigmentation in oculodermal melanocytosis].
AB  - Sixteen patients with oculodermal melanocytosis (Nevus of Ota, congenital ocular
      melanocytosis) were investigated for the location and the density of the ocular
      pigmentation, the increase in intraocular location and the malignant
      transformation. In all cases, conjunctivo-scleral dispersion pattern appeared as
      dispersed patches without any predominant site but a diffuse involvement of the
      angle. This finding points out that ODM may exhibit a characteristic dispersion
      pattern of pigmentation which is characteristic for ODM. For 14 patients
      intraocular pressures were < or = 18 mmHg, and for remaining 2 patients 21 and 22
      mm Hg. Glaucomatous optic disc or perimetric changes were not found in any
      patient. In one case, a histologically verified ciliary-choroidal melanoma at a
      superior-temporal site co-existed at the same location as the ODM.

PMID- 7738296
TI  - [Medium-term tolerance of anterior chamber implants in surgical treatment of
      severe myopia].
AB  - PURPOSE: To determine the tolerance of the corneal endothelium and of the haemato
      ocular barrier of phakic highly myopic eyes implanted with an anterior chamber
      I.O.L.ses. METHODS: Twenty-one phakic highly myopic were operated on with a
      Z.B.A.C.I.O.L. (manufactured by Domilens) by the same surgeon from May 1989 to
      June 1990. Complete examination including specular microscopy have been performed
      before surgery and each 6 months and a Laser Flare Cell Meter at 3 years was
      performed on 14 eyes. RESULTS: Two eyes of the same patient had to be explanted
      after surgery for important endothelial cell loss. The 19 others had no
      complication: no cataract, no loss of endothelial cells, no retinal detachment.
      14 eyes examined with a Laser Cell Flare Meter had results within normal limits.
      So, 19 out of 21 eyes implanted for high myopia with Z.B.A.C.I.O.L. have
      excellent results 4 years after surgery. CONCLUSION: Regarding these results, it
      seems possible to use this technique again with the new designed Anterior Chamber
      I.O.L.. Rigorous follow-up of all the implanted eyes is however required.

PMID- 7738297
TI  - [Interstitial keratitis and Cogan syndrome].
AB  - Cogan's syndrome consists of non syphilitic interstitial keratitis associated
      with vestibuloauditory dysfunction. This syndrome is rare and very few cases have
      been reported since Cogan's first characterization in 1945. We present the case
      of a 24-year-oldman with a history of recurrent access of arthralgia and
      glomerulonephritis. Bilateral corneal disease consists of peripheral whitish
      patchy opacities in deep stroma. The patient also shows bilateral severe
      deafness, fever, meningeal and tetrapyramidal syndrome. Ocular involvement
      responds well to corticosteroids therapy but hearing loss is severe and often
      irreversible.

PMID- 7738298
TI  - [Orbital lymphangioma: a clinical and radiological entity. Apropos of a case].
AB  - We reported on the case of a seven years-old boy suffering from an acute
      unilateral proptosis. Diagnosis of orbital lymphangioma was made with Magnetic
      Resonance Imaging (MRI) showing an intra-tumoral hemorrhage in a vascular tumor
      unrelated to general circulation. Authors underlined the interest of MRI due to
      its unique ability to characterize hemorrhage with hemodynamic isolation and to
      plan therapeutic approach. Even controversial, conservative management remained
      the best choice but surgery should be considered if vision is threatened.

PMID- 7738299
TI  - [Asymmetric radial keratotomy for low-grade myopia].
AB  - Thirty patients (47 eyes) underwent a radial keratotomy for low myopia (from 
      0.75 to -2.5 D). Surgical technique was as follows: optical zone between 3.0 and
      4.5 mm according to the degree of the myopia; two radial incisions in vertical
      superior and nasal horizontal meridian. The incisions were full thickness,
      obtained either with the "Russian" (centripetal) technique or with a centrifugal
      technique, but using a special designed knife. Mean refractive result was 1.73 D.
      For low myopia, our technique seems less traumatic and the refractive effect more
      rapidly steady.

PMID- 7738300
TI  - [Treatment of central serous chorioretinopathy].

PMID- 7738301
TI  - [Organ culture preservation of the human cornea at +31 degrees C and risk of
      infection].
AB  - PURPOSE: In order to reduce the risk of infection, we analyzed each stage of
      conservation of human cornea in organ culture at +31 degrees C. METHODS: This
      epidomiological study was conducted in 266 human corneas preserved in organ
      culture between January 1991 and December 1993. There were 3 stages: In the
      period of preservation (analysis of the contaminated medium), Before clinical use
      of the graft (analysis of the preservation medium), After the penetrating
      keratoplasty (analysis of the corneo-scleral rim and the transportation medium).
      The bacteriological media used were thioglycolate broth, trypticase soja and
      Sabouraud. RESULTS: In 266 storage media, 42 (15.7%) cultures are positive. The
      most commonly found organism was Staphylococcus aureus (21.4%). At the end of the
      conservation procedure, all of the cultures of the media were sterile (n = 165).
      After penetrating keratoplasty, 8 cultures were positive for the transportation
      medium and the corneo-scleral rim (5.1%), 3 cultures were positive for the corneo
      scleral rim only (1.9%) and 5 cultures were positive (3.2%) for the
      transportation medium without contamination of the corneo-scleral rim.
      CONCLUSION: Preservation at +31 degrees C in organ culture of human corneas
      allows elimination of the contaminated or potentially contaminant corneas before
      an eventual transplantation. In our experience, the risk of infection is
      especially situated in the period of preservation which shows the insuffiency of
      the decontamination procedures or the antibiotical content of the medium and
      probably the virulence of the organisms in donors hospitalized for long period.

PMID- 7738302
TI  - [Traumatic hyphema caused by contusion in Zaire].
AB  - PURPOSE: To study the clinical characteristics of hyphema. METHODS: Records of
      all 57 consecutive patients with traumatic hyphema due to non perforating ocular
      injury seen during a ten-year period (from 1982 to 1991) were reviewed. All
      patients were outpatients and were treated with topical application of
      corticosteroids with or without topical application of 0.5 or 1% atropine sulfate
      and antibiotics. For an intraocular pressure greater than 24 mmHg, topical
      timolol maleate 0.5% and, if necessary, oral acetazolamide sodium were used.
      RESULTS: There were 49 (86%) male and 8 (14%) female for sex ratio of 6:1. The
      average age of patients was 20.2 years (range, 2 to 61 years). Blows were
      responsible for injury in 53%; projectiles for 30% and explosions for 7% of all
      hyphemas. The most common associated injuries to the eye included cornea edema
      (40%), cataract (36%) and mydriasis (26%). Posterior synechiae (25%) and blood
      staining of the cornea (22%) were the most frequent complications that occurred.
      Secondary haemorrhage occurred in 7% of the cases. CONCLUSIONS: Heavily pigmented
      eye, proptosis, paucity of facilities for care may be responsible of the high
      rate of complications.

PMID- 7738304
TI  - [Outcome of Behcet disease in ophthalmological milieu in Morocco].
AB  - We treated 123 patients with Behcet's disease during a period of 10 years (1984
      1993). The ocular lesions include uveal lesions especially the posterior lesions
      and vascular retinal. Uveitis was total in 72% of cases. Periphlebitis occurred
      in 51% of cases, vein occlusion in 10% of cases, macular oedema in 16% and
      papillary oedema in 10%. Clinical course and prognosis were studied. The
      functional prognosis is poor as such lesions may lead to blindness, particularly
      due to papillary oedema maculopathy. The treatment used is based on
      immunosuppressive and corticoid steroid drugs.

PMID- 7738305
TI  - [Arterial hypotension in glaucoma of normal or moderately high pressure].
AB  - BACKGROUND: Arterial hypotension, by decreasing blood flow in the optic nerve
      head, may be a risk factor for glaucomatous damage. The purpose of this study was
      to compare blood pressure in different types of glaucoma patients, using
      ambulatory recording. METHODS: An ambulatory blood pressure recording was
      performed in 55 glaucoma patients over a 24-hour period. Two groups of patients
      could have been differentiated according to pretreatment intra-ocular pressure
      level: a group of 38 patients (GPNM) with normal or moderately elevated intra
      ocular pressure, and a group of 17 patients (GPH) with high intra-ocular
      pressure. RESULTS: A statistically significant different lower blood pressure was
      found in group GPNM for: diastolic mean blood pressure (76.4 versus 81.4 mmmHg p
      = 0.05), diastolic nocturnal (71.8 versus 78.1 mmHg p = 0.025), and for some
      hourly intervals: from 2:00 to 3:00 (p = 0.008), 8:00 to 9:00 (p = 0.01) and
      15:00 to 18:00 (p = 0.03). The mean lowest readings were lower (p < 0.05) in
      group GPNM (95.8/54.4 versus 102/59.9 mmHg). The percentage of low readings (9.9%
      versus 5.1% p = 0.01) and systolic drops (0.226 versus 0.192 p = 0.018) were also
      higher in this group. CONCLUSION: Hypoperfusion of optic nerve head may be a
      significant factor in glaucomatous damage by compromising blood supply. It is
      important to identify arterial hypotension when examining of normal or moderately
      elevated pressure glaucoma patients, and ambulatory monitoring of blood pressure
      is currently the best test. These episodes should be taken into consideration,
      especially when initiating systemic antihypertensive therapy, in order to
      maintain, as well as possible, perfusion of the optic nerve head.

PMID- 7738306
TI  - [When should patients with glaucoma be operated on?].

PMID- 7738303
TI  - [The cornea of diabetics].
AB  - PURPOSE: The aim of the study is to investigate corneal sensitivity and the risk
      factors of corneal hypoesthaesia in diabetics. METHODS: General examination and
      full ophthalmologic examination completed by exploration of corneal sensitivity
      were performed in one hundred thirty diabetic patients. RESULTS: Eleven per cent
      of patients showed microkystic oedema, whereas corneal hypoesthaesia was found in
      45% of cases. Corneal hypoesthaesia was correlated with the duration and balance
      of diabetic mellitus, the age of patients and the presence of diabetic
      retinopathy. On the other hand, peripheral neuropathy was found in 88% of cases.
      CONCLUSION: Ophthalmologic examination of diabetics should not be limited to
      retina only but should also include the entire eye ball and especially the cornea
      in patients with high risk.

PMID- 7738307
TI  - [Neuropapillitis in Behcet disease. A case].
AB  - The authors report the case of a 34 year old woman, who developed acute
      neuropapillitis, which appeared to be the first ophthalmologic manifestation of
      Behcet's disease. One year later, this patient recurred with another neuro
      ophthalmologic sign: a sixth nerve palsy.

PMID- 7738308
TI  - [Ocular vasospasm in cold provocation test and primary vascular acrosyndrome].
AB  - An ocular vasospasm induced by cold has been searched among 8 patients carrying
      primary vasospastic disease without any ocular pathology. Ocular vasospasm which
      is characterized by visual field defect was searched with Statpac 24-2 test using
      HUMPHREY autoperimeter. A baseline visual field was performed first, then a
      second after provocation by dipping the hand in cold water (13 degrees) and a
      third after oral administration of 10 mg of Nifedipine. Two patients had ocular
      vasospasm that regressed after Nifedipine administration. These two patients
      might have a higher risk to develop normal tension glaucoma.

PMID- 7738309
TI  - [Corneal ulcer and Behcet disease. Apropos of a case].
AB  - We report a case of a peripheral corneal ulcer that occurred to a 33 years old
      female with a Behcet's disease. This patient had a previous history of viral
      keratoconjunctivitis with subepithelial nodules one year ago. The type, aspect
      and localization of the ulcer suggested an immunologic origin. The evolution was
      favourable after systemic and local steroid therapy. The other aetiologies of
      such ulcer are discussed by the authors.

PMID- 7738310
TI  - [Solitary oligodendroglioma of the optic nerve. Apropos of a case].
AB  - Proptosis, decreased vision and oculo-motor palsies developed in the left eye of
      a 14-year-old girl, without neurofibromatosis signs. Computed tomographic (CT)
      Scans of the head and orbit showed a large fusiform expansion of the left optic
      nerve without intracranial involvement. Magnetic resonance imaging improved
      contrast resolution over CT Scanning. A neurosurgical approach was performed and
      the optic nerve was resected from the back of the globe to the intracranial
      portion. Microscopic sections demonstrated oligodendroglioma, an unusual form of
      optic nerve glioma.

PMID- 7738311
TI  - [Technique for the resection of the superior oblique muscle].

PMID- 7738312
TI  - [Treatment of vitreous flange, complication of cataract extraction].

PMID- 7738313
TI  - [Cytomegalovirus retinitis in children with AIDS acquired through materno-fetal
      transmission].
AB  - PURPOSE: To describe the clinical feature and the outcome of CMV retinitis in
      children with vertically transmitted HIV infection. RESULTS: Five case-reports of
      cytomegalovirus retinopathy are described. These children from eight month-old to
      seven and a half year-old (median age at diagnosis 52 months) had been
      perinatally contaminated by the human immuno-deficiency virus. The ophthalmic
      signs included only a red eye for one patient. The clinical signs were similar to
      the adult's retinopathy. At the opposite the differences were emphasized like the
      clinical onset with a delayed diagnosis. Mean follow-up since diagnosis is 8
      months with 3 patients still alive. CONCLUSION: CMV retinitis in vertically
      transmitted AIDS can occur early in childhood and must be checked systematically
      in the patients with low CD 4 count because of the usual asymptomatic onset.

PMID- 7738314
TI  - [Postoperative choroidal hemorrhage. Surgical indications].
AB  - PURPOSE: Through analysis of 18 cases of postoperative suprachoroidal
      haemorrhage, we discuss indications for surgical treatment, especially for
      vitrectomy. Time of surgery depends on complete lysis of the clot (mean of 7
      days) determined by echography. METHOD: Eighteen post-operative cases complicated
      with supra-choroidal hemorrhages were operated on between January 1988 and July
      1992: 7 cases occurred after cataract extraction, 6 after filtering surgery and 5
      after retinal detachment repair. Treatment, in all cases, included evacuation of
      the haematoma. A vitrectomy was associated in 14 cases using internal tamponade
      in 12 cases: 9 with silicone oil and 3 with SF6. The latest cases treated by
      vitrectomy benefited by the use of liquid perfluoro-carbons. RESULTS: We had
      successful anatomical results in 14 eyes. For 12 eyes which kept functional
      vision, mean postoperative visual acuity was 20/100. We point out the high rate
      of secondary retinal detachment complicated by PVR (7 cases) and eventually
      responsible for treatment failure in 4 cases. CONCLUSIONS: Satisfactory results
      can be obtained in treating post-operative choroidal haemorrage by appropriate
      use of vitrectomy: indications include incarceration of vitreous in the
      filtration bleb or in the cataract incision, vitreous haemorrhage, rhegmatogenous
      and/or traction retinal detachment. The echography is of great value to determine
      timing of surgery by assessing completeness of clot lysis.

PMID- 7738315
TI  - Federal antitrust merger enforcement standards: a good fit for the hospital
      industry?
AB  - We examine the implications of the 1992 Horizontal Merger Guidelines for the
      hospital industry and subsequent policy statements that were developed for health
      care providers. Application of antitrust policy to hospitals has raised several
      concerns, mainly because many communities have few hospitals and economic forces
      in the industry are accelerating interest in intramarket mergers and provider
      network development. We address several issues, including the standing of
      hospitals relative to the market concentration thresholds of the merger
      guidelines, market concentration compared among challenged and unchallenged
      mergers of the 1980s, findings of previous research about the relationship
      between market concentration and competition in hospital markets, and differences
      in characteristics other than market concentration that are relevant to the
      merger guidelines among challenged and unchallenged mergers. We found that (1)
      the specific standards articulated in the merger guidelines do not provide good
      predictability of when a hospital merger challenge would occur, and (2)
      comparisons of challenged and unchallenged mergers in similarly structured
      markets suggest that enforcement actions may deviate in practice from the
      enforcement principles of the merger guidelines. We consider several options for
      refining antitrust enforcement policy. Refinement of enforcement policies is
      important given the industry restructuring that is likely through health care
      reform.

PMID- 7738316
TI  - The need for an antitrust policy for a health care industry in transition.

PMID- 7738317
TI  - Hospital mergers and antitrust enforcement.

PMID- 7738318
TI  - Reforming the British National Health Service: implementation problems in London.

PMID- 7738319
TI  - Political analysis and the welfare state: can we learn from history? Review
      essay.

PMID- 7738320
TI  - Medigap regulation: lessons for health care reform.
AB  - Congress enacted legislation in 1990 that dramatically changed the rules for
      selling supplemental health insurance, or "Medigap" policies, to the elderly.
      Most notably, policy coverage was standardized. Insurance carriers are allowed to
      sell only the ten specified packages of benefits, which reduces consumer choice
      but facilitates comparison shopping. This legislation is important in its own
      right and also offers lessons for U.S. health care reform. To examine the changes
      brought about by this legislation and analyze their implications for health care
      reform, we conducted site visits to nine states and interviewed insurer
      representatives, executive branch officials, congressional staff, and various
      interest groups for two years.

PMID- 7738322
TI  - Nothing succeeds like the right kind of failure: postwar national health
      insurance initiatives in Canada and the United States.
AB  - Health insurance was one of the most influential social reforms on the immediate
      postwar agenda in Canada and the United States. In both cases, proposals for
      national health insurance were not implemented. This article traces the evolution
      of these legislative proposals of the 1940s and shows how the events of this
      pivotal decade set the stage for future health reform in the two countries. The
      analysis focuses on how political institutions condition the role of state actors
      and the articulation of societal groups, and particularly on the crucial
      differences in party systems and the role of parties in shaping health reform in
      the two countries. In the United States, a divided Democratic party and the
      imperatives of political compromise made forging a consensus around health
      insurance more difficult. In Canada, meanwhile, the presence of a social
      democratic third party led to a very different type of debate about health reform
      and opened the door for national health insurance.

PMID- 7738321
TI  - Balance billing under Medicare: protecting beneficiaries and preserving physician
      participation.
AB  - Medicare's experience with balance billing provides valuable lessons for policy
      making for national or state health care reform. Medicare developed several
      policies to encourage physicians to become participating providers who accept
      Medicare-allowed charges as payment in full. Only nonparticipating physicians are
      permitted to bill for additional amounts beyond that paid by Medicare, and there
      are limits on the amount of balance billing per claim. As shown by the analysis
      of claims presented in this article, Medicare has successfully provided financial
      protection to beneficiaries. In 1986, more than 60 percent of expenditures for
      physician services were on assigned claims for which there could be no balance
      billing; by 1990, 80 percent of expenditures were on assigned claims. Balance
      billing decreased by about 30 percent during the same period. Although these
      policies have been successful in reducing total expenditures for balance billing,
      they may not provide financial protection to the most economically vulnerable
      beneficiaries. Using survey and claims data, we found that the poor have lower
      balance billing expenditures for services provided by primary care physicians,
      but that there is no relationship between poverty status and balance billing
      expenditures for services of nonprimary care physicians. In addition, most low
      income beneficiaries are liable for balance bills. Under health care reform,
      adoption of Medicare's incentive-based approach with mandatory assignment for the
      poor would allow for some choice based on price and would provide financial
      protection for all consumers.

PMID- 7738323
TI  - Continuing care retirement communities: prospects for reducing institutional long
      term care.
AB  - Continuing care retirement communities (CCRCs) combine housing and long-term care
      (LTC) services, including personal and nursing home care. The amount of LTC that
      is prepaid varies by type of CCRC, with one-third offering extensive (fully
      prepaid) contracts for LTC. CCRCs are a potentially promising model for LTC
      delivery because they offer a full continuum of services and can substitute less
      expensive supportive care for institutional care. Using data on CCRCs, we tested
      one central hypothesis: Provision of supportive services, particularly when
      combined with capitation, reduces use of nursing home care. To test this
      hypothesis, we studied the effect of various contract types for LTC services
      offered by CCRCs and provision of support services on utilization of nursing home
      and personal care units. Compared with other types of CCRCs, those offering
      completely prepaid LTC coverage reduced use of nursing home care by 13 percent
      and personal care by 5 percent. CCRCs with prepaid LTC coverage did not use more
      stringent health screening at entry, so "cream-skimming" does not appear to
      explain this result. However, affordability is an important issue: CCRC residents
      with extensive contracts were wealthier than were other CCRC residents.

PMID- 7738324
TI  - Malpractice reform in the 1990s: past disappointments, future success?
AB  - State governments, the federal government, interest groups, and researchers have
      proposed various approaches to reform the malpractice system. Malpractice reforms
      fall into two generations. First-generation reforms are those adopted by states
      beginning in the 1970s chiefly to reduce claim frequency and severity and thereby
      improve the malpractice system primarily from the perspective of providers and
      insurers. Scholars and interested constituencies developed second-generation
      reforms, such as use of medical practice guidelines to set the standard of care,
      various no-fault approaches, enterprise liability, mandated alternative dispute
      resolution, and scheduling damages, to streamline the adjudication and
      compensation system from the perspective of claimants and providers. Research
      indicates that first-generation reforms have not been very effective in achieving
      the compensation and deterrence goals of tort, whereas second-generation reforms
      hold greater promise of doing so. This analysis of state and federal legislation
      indicates that states, and more recently Congress, have been reluctant to adopt
      second-generation reforms but continue to promote and/or adopt first-generation
      reforms. The strength of the provider lobby, concerns of health care reformers
      about the relationship between defensive medicine and health system costs, and
      lack of an organized consumer force for second-generation malpractice reform are
      important explanations of why the states and Congress have not embraced second
      generation reforms. Furthermore, federal and state legislative interest in second
      generation reforms, although never high, is waning in the current health care
      reform debate.

PMID- 7738325
TI  - Revisiting the behavioral model and access to medical care: does it matter?
AB  - The Behavioral Model of Health Services Use was initially developed over 25 years
      ago. In the interim it has been subject to considerable application, reprobation,
      and alteration. I review its development and assess its continued relevance.

PMID- 7738326
TI  - Work and family roles and psychological well-being in urban China.
AB  - A theoretical framework that delineates the relationships between work and family
      roles and psychological well-being is derived from U.S. research and utilized to
      examine the relationships of work and family stress with psychological well-being
      in urban China. Data from a sample of 733 married and employed individuals in
      urban Shanghai confirm the general model of the link between work and family
      stress and psychological distress. Due to the centrality of work roles for the
      Chinese, work stress exerts a stronger relationship on psychological well-being
      than does family stress. Furthermore, the Chinese are more vulnerable to stress
      arising from interpersonal conflicts than from role demands. In addition, gender
      differences are found in the relationship between role stress and distress. Women
      tend to experience more family demands than men. Women's mental health status is
      tied similarly to stress arising from work and family roles, whereas men are more
      vulnerable to work stress than family stress. However, Chinese women do not
      report significantly greater generalized distress than men.

PMID- 7738327
TI  - Minority stress and mental health in gay men.
AB  - This study describes stress as derived from minority status and explores its
      effect on psychological distress in gay men. The concept of minority stress is
      based on the premise that gay people in a heterosexist society are subjected to
      chronic stress related to their stigmatization. Minority stressors were
      conceptualized as: internalized homophobia, which relates to gay men's direction
      of societal negative attitudes toward the self; stigma, which relates to
      expectations of rejection and discrimination; and actual experiences of
      discrimination and violence. The mental health effects of the three minority
      stressors were tested in a community sample of 741 New York City gay men. The
      results supported minority stress hypotheses: each of the stressors had a
      significant independent association with a variety of mental health measures.
      Odds ratios suggested that men who had high levels of minority stress were twice
      to three times as likely to suffer also from high levels of distress.

PMID- 7738328
TI  - Work and well-being: gender differences in the psychological consequences of
      employment.
AB  - Differential exposure and vulnerability to social roles and role characteristics
      have been suggested as accounts for gender differences in well-being. This paper
      proposes a refinement of these models that incorporates the indirect effect of
      roles through intervening social and psychological resources. These reformulated
      models provide the framework for an analysis of gender differences in the
      psychological consequences of work that estimates the direct and indirect effects
      of two job conditions, control and complexity, on two dimensions of well-being.
      Results reveal patterns of differential exposure, but also suggest some gender
      differences in the intervening variables through which work conditions influence
      well-being. These differences occur primarily in the proximate effects of self
      esteem and social integration on distress and happiness.

PMID- 7738329
TI  - Identity-relevant events and psychological symptoms: a cautionary tale.
AB  - I examine the psychological impact of negative and positive events in roles that
      individuals view as salient or important for self-conception. Events in highly
      salient role-identity domains (identity-threatening and identity-enhancing
      events) should have greater effects on symptoms than those in less salient
      domains. Data come from interviews with a stratified two-wave panel sample of 532
      married and divorced urban adults. Contrary to expectations, the influences of
      events on changes in psychological distress and alcohol/drug use were not
      dependent on the importance of the role-identity to the individual. Exploratory
      qualitative analyses suggested several reasons why. I reformulate the identity
      relevant stress hypothesis in light of these observations, and argue that
      contextual details about events are required to test the revised hypothesis
      adequately. The complex influences of stressors on perceptions of identity
      salience need further examination as well.

PMID- 7738330
TI  - Work alienation and problem alcohol behavior.
AB  - Using a sample of production workers from union, nonunion, producer cooperative,
      and employee stock ownership plan (ESOP) wood products mills in the Northwest, we
      test the general proposition that work alienation, defined as low job autonomy,
      low use of capacities, and lack of participation in decision-making in the
      workplace, is associated with heavy drinking and negative consequences from
      drinking. We find that the general proposition is supported, but that the
      pathways tend to be indirect rather than direct, mediated by feelings of job
      satisfaction and respondents' beliefs about the utility of drinking as a means of
      coping.

PMID- 7738331
TI  - Third party has no role in patient-physician relationship.

PMID- 7738332
TI  - Shared 'vision' results in new network. Interview by Bob Carlson.

PMID- 7738333
TI  - How to keep your practice running smoothly.

PMID- 7738334
TI  - Approach to the patient with a soft tissue mass.

PMID- 7738335
TI  - Indianapolis hospitals standardize changes in prothrombin time testing.

PMID- 7738336
TI  - Epidemiology of Pseudomonas aeruginosa infection and the role of contamination of
      the environment in the Danish Cystic Fibrosis Centre.
AB  - In order to identify the possible reservoirs and routes of cross-infection with
      Pseudomonas aeruginosa, samples were collected during a six-week period in autumn
      1992 from patients, their visiting parents, staff and the inanimate environment
      of the Danish Cystic Fibrosis (CF) Centre and from a control ward with common
      paediatric diseases. All the P. aeruginosa strains were phage typed and
      serotyped. From 240 CF patients, 310 strains of P. aeruginosa were isolated, and
      of these 283 (91.3%) belonged to the polyagglutinable phenotype, most often with
      a short phage type (31/188 or 109). P. aeruginosa was isolated from only six
      (0.6%) of 1000 swabs taken from the environment. These six environmental strains
      and 20 P. aeruginosa strains from CF patients with identical serotype and phage
      type were examined with pulsed field gel electrophoresis. None of the patients
      harboured strains similar to the environmental strains, indicating the present
      isolation procedure and hygienic precautions were effective in our CF centre, and
      prevented contamination of the environment with P. aeruginosa.

PMID- 7738337
TI  - Evolution of bacterial susceptibility to antibiotics during a six-year period in
      a haematology unit.
AB  - A knowledge of the bacterial ecology of a haematology unit should help in the
      management of the febrile patient with or without neutropenia. We studied the
      prevalence and the susceptibility profiles of bacteria isolated during a six-year
      period among patients hospitalized in a 44-bed haematology unit. Antibiotic use
      over this period was also studied. The most prevalent bacteria were coagulase
      negative staphylococci (CNS) (35.1%), Escherichia coli (11.4%), Staphylococcus
      aureus (9.9%), Enterococcus spp. (8.2%), and Pseudomonas aeruginosa (7.5%). The
      susceptibility of CNS to oxacillin decreased from 67-44% over six years, while
      that of enterobacteriaceae to amoxycillin and piperacillin was reduced by about
      50%. P. aeruginosa susceptibility to ceftazidime remained remarkably stable at
      around 90%, despite extensive empirical use. Imipenem and ciprofloxacin were used
      restrictively and ceftazidime-resistant P. aeruginosa remained susceptible to
      these two agents in most cases. Our antibiotic policy was found to be compatible
      with the frequency of the bacterial strains isolated in our department and with
      their susceptibility profiles.

PMID- 7738338
TI  - Epidemiological typing of clinically significant strains of coagulase-negative
      staphylococci.
AB  - This study was undertaken to determine the characteristics of 202 isolates of
      coagulase-negative staphylococci (CNS) isolated from 78 patients (two-seven per
      patient) using biochemical identification, bacteriophage susceptibility patterns,
      reverse-typing, plasmid profiles, antimicrobial susceptibility testing and slime
      production. All the strains could be typed by using the six markers
      consecutively. In addition, we have been able to deduce the similarity of 58
      strains from 24 patients by means of one marker or another (these are similar or
      different strains within one patient but not between one patient and another).
      The use of a combination of markers is the ideal method for typing the strains;
      thus making it possible to confirm if two or more isolates from the same patient
      are similar or not and if they produce infection or are simple contaminants.

PMID- 7738339
TI  - Bacterial and viral removal efficiency, heat and moisture exchange properties of
      four filtration devices.
AB  - Four devices used for filtration of microorganisms and/or for heating and
      moistening the ventilated air during mechanical ventilation were evaluated. This
      evaluation included measurement of bacterial and viral removal efficiency, heat
      and moisture exchange properties, dead space and air flow resistance. The devices
      included: Pall BB50T and DAR Sterivent (filtration devices); DAR Hygrobac and
      Gibeck Humid-vent [heat and moisture exchangers (HMEs)]. The two devices which
      are primarily conceived as filters, had the highest bacterial and viral removal
      efficiency (titre reduction of 10(5)-10(6) for bacteria and of 10(4)-10(5) for
      viruses), while removal efficiencies of the HME devices were lower: titre
      reduction of 10(4) for bacteria and 10(1)-10(3) for viruses. As expected, heat
      and moisture output of HMEs was better than that of filters. In mechanical
      ventilation, dead space and air flow resistance are important properties of
      devices, which might disturb efficient ventilation. There were only minor
      differences in dead space and air flow resistance. Resistance to airflow in the
      HMEs was increased by nebulization of medication (mesna) unlike that of the
      filters.

PMID- 7738340
TI  - Epidemiology and clinical spectrum of pneumococcal infections: an Israeli
      viewpoint.
AB  - We performed a prospective study of consecutive pneumococcal infections
      documented during a six-month period in our clinical microbiology laboratory. A
      total of 59 cultures obtained from clinically significant specimens of 58
      patients were positive for Streptococcus pneumoniae. Relative penicillin
      resistance occurred in 14 strains (24%) and only one (1.7%) was highly resistant
      to penicillin (minimum inhibitory concentration = 2.0 micrograms ml-1).
      Resistance to common alternative drugs was not found. Serotypes were of a wide
      variety, however types 1, 7 and 14 predominated (60% of all blood culture
      isolates). Twenty-three patients with community-acquired infection required
      hospitalization. Nosocomial pneumonia developed in three additional cases (14%).
      Invasive disease was diagnosed in 24 patients with pneumonia representing the
      most common infection (22 patients). Pneumonia was characterized by a high
      incidence of serious underlying diseases (82%) and associated bacteraemia (68%).
      Compared with controls, patients with penicillin-resistant pneumococcal pneumonia
      had a significantly higher incidence of previous hospitalizations and use of
      antibiotics (57 vs. 7%, P = 0.02). The overall case fatality rate was high (36%)
      and did not differ significantly between patients with pneumonia due to resistant
      and susceptible strains. The epidemiology and clinical spectrum of serious
      pneumococcal infections in Israel is similar to those described in many parts of
      the world, but high level resistance to penicillin and to other alternative drugs
      is still rare.

PMID- 7738341
TI  - Stethoscope contamination in the neonatal intensive care unit.
AB  - The level of contamination of stethoscopes used in a neonatal intensive care unit
      was studied, along with the practices used for cleaning these items. A policy of
      alcohol cleaning was introduced and the effect of this change on the level of
      bacterial growth was observed after a six-week period. It was found that 71% of
      stethoscopes had a significant bacterial growth and that this was reduced to 30%
      after the cleaning procedure change (P < 0.05). Stethoscopes and other equipment
      are a potential source of nosocomial infection on the neonatal intensive care
      unit.

PMID- 7738342
TI  - A hospital outbreak of Clostridium perfringens food poisoning--implications for
      food hygiene review in hospitals.
AB  - An outbreak of Clostridium perfringens (C. perfringens) food poisoning affected
      17 of 44 (38.6%) patients interviewed on two hospital wards. A case-control study
      showed a statistically significant association between the consumption of roast
      pork and illness (P < 0.01). C. perfringens type A, untypable serotype, was
      isolated from samples of pre-cooked vacuum sealed pork supplied by a local meat
      producer. Faults were noted in the food production process at the factory. Cuts
      of meat were too large and equipment to ensure rapid cooling of cooked meat was
      not installed. Cost improvements taken by hospitals, such as the use of
      commercially cooked meat, may not be consistent with the highest standards of
      food safety. Amendments to the District Catering Policy were implemented to
      prevent further outbreaks.

PMID- 7738343
TI  - Clostridium difficile diarrhoea.

PMID- 7738344
TI  - The uptake and release of molecular iodine by the skin: chemical and bactericidal
      evidence of residual effects caused by povidone-iodine preparations.
AB  - The residual effect of iodine-based disinfectants is caused by a dynamic back
      diffusion which is the reverse of the absorption occurring during application. A
      very sensitive photometric method was used to measure the iodine flux of the back
      diffusion after treating the skin with povidone-iodine preparations and Lugol's
      solution. After removal of the preparation the intensity of the iodine flux
      decreases with time and correlates with the amount of iodine being resorbed. The
      latter depends on the concentration of free molecular iodine of the preparation,
      the contact time and the thickness of the horny layer of the treated skin. With
      Lugol's solution (approximately 170 ppm free molecular iodine) iodine flux could
      be observed 12-24 h after an application of 20-60s, while with low-level povidone
      iodine preparations (0.5-20 ppm free iodine) the measurable flux lasted only 0.5
      1 h after an application time of 3 min. The bactericidal activity of the back
      diffusing iodine from skin previously treated with a commercial povidone-iodine
      preparation was assayed by using an inoculation with Micrococcus luteus. This
      showed a logarithmic reduction of 0.4 in bacterial concentration. Since the skin
      was washed with soap for 1 min after application this bactericidal action
      reflected the residual effect of the back-diffusing iodine.

PMID- 7738345
TI  - Immunoglobulin E-binding structures on antigen-presenting cells present in skin
      and blood.
AB  - In atopic individuals, cutaneous antigen-presenting cells (APC), i.e., Langerhans
      cells and dermal dendritic cells, frequently display anti-IgE reactivity.
      Although earlier observations suggested that this phenomenon results from the
      binding of (complexed) IgE to the low-affinity IgE receptor (Fc epsilon
      RII/CD23), we and others demonstrated recently that Langerhans cells, dermal
      dendritic cells, and peripheral blood monocytes from atopic individuals can bind
      monomeric IgE via the high-affinity receptor for IgE (Fc epsilon RI). These new
      observations re-stimulated investigations aiming to unravel the nature and
      functionality of the relevant in vivo IgE-binding moiety(-ies) on APC. New data
      demonstrate that Fc epsilon RI, both quantitatively and qualitatively, is the
      pivotal serum IgE-binding structure on APC of atopics and, even more important,
      that Fc epsilon RI on APC functions as an allergen-focusing molecule. Thus, it is
      likely that allergens may be more efficiently taken up, processed, and presented
      to T cells after targeting to APC via Fc epsilon RI as compared with allergen
      binding to APC in the conventional manner. In vivo, Fc epsilon RI-IgE-dependent
      allergen presentation may critically lower atopic individuals' threshold to mount
      allergen-specific T-cell responses. This would result in the perpetuation of
      allergen-specific IgE production (type I reactions) and perhaps even the
      occurrence of T-cell-mediated, delayed-type hypersensitivity reactions in
      allergen-exposed tissues.

PMID- 7738346
TI  - Plakoglobin binding by human Dsg3 (pemphigus vulgaris antigen) in keratinocytes
      requires the cadherin-like intracytoplasmic segment.
AB  - Desmogleins are transmembrane desmosomal cadherins. Two desmogleins, Dsg3 and
      Dsg1, have been shown to bind plakoglobin, an intracytoplasmic (IC) desmosomal
      plaque protein. This binding may be critical for desmosome assembly or stability.
      The IC domain of desmogleins consists of subdomains that are either desmoglein
      specific or homologous with the IC region of classical cadherins. Here we
      identify the domains of human Dsg3 that are critical for plakoglobin binding in
      human keratinocytes. We constructed eukaryotic expression vectors containing
      chimeric cDNAs that encode the extracellular domain of mouse E-cadherin (Ecad)
      with the transmembrane and IC domains of Dsg3, with increasing truncations
      eliminating various IC subdomains from the carboxy-terminus. These constructs
      were used for transient transfection of HaCaT cells. Extracts were subjected to
      immunoprecipition with an anti-mouse Ecad antibody (that does not precipitate
      human Ecad), thus precipitating the chimeric protein and any tightly associated
      plakoglobin. Co-precipitation of plakoglobin was confirmed by immunoblotting.
      These data show that the desmoglein-specific IC subdomains are not necessary for
      plakoglobin binding, but the carboxy-terminal 87 amino acids of the IC-cadherin
      like segment subdomain are critical. Finally, we confirmed these results outside
      cells with in vitro transcription and translation, which also demonstrates that
      the Dsg3-plakoglobin interaction is direct and does not depend on other cellular
      factors. These results underscore the importance of a region, highly conserved in
      all desmogleins, in the carboxy terminus of the IC-cadherin-like subdomain for
      the localization of plakoglobin to desmosomes.

PMID- 7738347
TI  - T-cell-receptor repertoire in chronic plaque-stage psoriasis is restricted and
      lacks enrichment of superantigen-associated V beta regions.
AB  - Preferential usage of certain T-cell receptors by the lymphocytic infiltrate in
      psoriasis might indicate the involvement of an antigen in the pathogenesis of
      this disease. However, to date there are no data on the complete T-cell-receptor
      V alpha and V beta repertoire in psoriatic patients. We therefore compared the
      usage of T-cell-receptor variable regions in blood and skin of 10 patients with
      chronic plaque-stage psoriasis by means of semiquantitative polymerase chain
      reaction. Additionally, HLA class II alleles were analyzed by means of sequence
      specific oligonucleotide typing. A considerable restriction of the T-cell
      receptor repertoire was observed in the skin, where up to 20% of the variable
      regions present in the blood were not detectable. This was true for both alpha-
      and beta-chains. However, no interindividually constant pattern of T-cell
      receptor restriction was deducible. Inconsistently, a certain preferential usage
      of some beta chains occurred within the cutaneous compartment. This report on the
      complete T-cell-receptor V alpha and V beta repertoire in psoriasis documents the
      restricted receptor repertoire of infiltrating T cells and a lack of enrichment
      of superantigen-associated V beta regions. Thus superantigens seem not to play a
      pathogenetically relevant role in chronic plaque-stage psoriasis.

PMID- 7738348
TI  - Interleukin-1 alpha stimulates keratinocyte migration through an epidermal growth
      factor/transforming growth factor-alpha-independent pathway.
AB  - Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha)
      stimulate keratinocyte migration on collagen by up-regulating the alpha 2 subunit
      of the collagen integrin, alpha 2 beta 1. Interleukin-1 (IL-1) is an autocrine
      factor, produced by keratinocytes themselves, that is modulated by ultraviolet
      light and increases the proliferative potential of keratinocytes in culture. The
      autocrine nature of keratinocyte-derived IL-1 alpha is emphasized by the fact
      that it induces the keratinocyte to synthesize IL-1 alpha and TGF-alpha, a
      cytokine known to induce keratinocyte motility. Further, topical application of
      IL-1 alpha has been shown to promote wound healing in animals. In this study, we
      used a well-defined keratinocyte migration assay to assess the effect of IL-1
      alpha on keratinocyte motility and to examine whether the IL-1 alpha/TGF alpha
      pathway is involved. The addition of recombinant human IL-1 alpha to
      keratinocytes produced a statistically significant and concentration-dependent
      increase in migration on matrices of collagen types I and IV, but not on laminin.
      Maximal levels of keratinocyte migration obtained on these matrices with IL-1
      alpha were comparable to those obtained with stimulation by EGF and TGF-alpha.
      The effects of TGF-alpha and IL-1 alpha on keratinocyte migration are additive;
      however, the maximal level of migration achieved by using IL-1 alpha and TGF
      alpha in combination never exceeds the maximal level of migration found by using
      either cytokine alone. The time course of keratinocyte migration induced by IL-1
      alpha is delayed (onset of migration 9-12 h after addition) as compared with that
      induced by TGF-alpha (onset of migration 6-9 h after addition) even if the cells
      are preincubated in IL-1 alpha. Flow cytometry analysis demonstrated no change in
      surface expression of integrin subunits, specifically that of integrin subunit
      alpha 2, previously shown to be up-regulated by EGF/TGF-alpha. These results
      suggest that IL-1 alpha stimulates keratinocyte migration on collagen via a
      mechanism distinct from that of EGF/TGF-alpha.

PMID- 7738349
TI  - Cells with UV-specific DNA damage are present in murine lymph nodes after in vivo
      UV irradiation.
AB  - Ultraviolet radiation is absorbed in the skin, especially in the epidermis. After
      ultraviolet irradiation the number of major histocompatibility complex class II+,
      adenosine triphosphatase+ Langerhans cells and Thy-1+ dendritic epidermal cells
      in the epidermis decreases. Whether this decrease is due to migration of these
      cells or to loss of membrane markers is not clear. To address this question we
      have used the monoclonal antibody H3 directed against cyclobutyl thymine dimers-a
      form of DNA damage that is specifically induced by ultraviolet radiation-to
      investigate whether H3+ cells are present in the draining lymph nodes of the skin
      after ultraviolet irradiation of hairless, inbred mice (HRA/Skh). After a single
      dose of ultraviolet radiation (Westinghouse FS40, 1.5 kJ/m2), H3+ cells were
      present in the paracortex of the draining lymph nodes. No positive cells were
      found in the blood of irradiated mice. These results suggest that the H3+ cells
      in the lymph nodes originate from the skin. The number of H3+ cells in the
      draining lymph nodes increased the first 24 h after irradiation and then
      stabilized. Immunohistochemical double staining revealed that all H3+ cells were
      major histocompatibility complex II+, and that only a fraction of the cells were
      NLDC-145 positive. No V gamma 3 T-cell receptor bearing cells could be found in
      the lymph nodes after UV irradiation of the skin.

PMID- 7738350
TI  - Isolation of a unique melanogenic inhibitor from human skin xenografts: initial
      in vitro and in vivo characterization.
AB  - Previously, split-thickness human skin grafted onto athymic mice has been shown
      to become markedly hyperpigmented, but the factor(s) responsible for this
      hyperpigmentation had not been isolated. The present study describes the
      isolation and characterization of a potent melanogenic inhibitor from grafted
      human skin. Extracts from grafted skin inhibited, in a concentration-dependent
      manner, tyrosinase activity of normal human melanocytes and of Cloudman S91
      murine melanoma in culture. Sodium dodecylsulfate-polyacrylamide gel
      electrophoresis analysis of extracts from pre- and post-grafted skin demonstrated
      the presence of a protein doublet of approximately 14 kD exclusively in the post
      grafted skin. This protein inhibited both tyrosinase activity and cellular
      proliferation in a concentration-dependent manner. The inhibition of tyrosinase
      activity in normal human melanocytes was 53% at 0.5 microgram/ml concentration,
      whereas this inhibition was almost complete in murine melanoma cultures at 1.0
      microgram/ml. The protein did not inhibit either cellular proliferation or
      protein synthesis in normal human fibroblast cultures, and therefore may act
      specifically on melanocytes. Injections of the inhibitor corresponded with a
      delay and reduction in the quantity of pigment in human skin 2 weeks after
      grafting. Multiple injections of the inhibitor into the hyperpigmented xenografts
      (20 weeks after grafting) reversed the hyperpigmentation with no observable
      inflammatory or toxic responses. The results indicate that hyperpigmented human
      skin xenografts contain a potent inhibitor of melanogenesis and melanocyte
      proliferation.

PMID- 7738351
TI  - Increased expression of vascular permeability factor (vascular endothelial growth
      factor) in bullous pemphigoid, dermatitis herpetiformis, and erythema multiforme.
AB  - Vascular permeability factor (VPF), also known as vascular endothelial growth
      factor (VEGF), plays an important role in the increased vascular permeability and
      angiogenesis associated with many malignant tumors. In addition, VPF/VEGF is
      strongly expressed by epidermal keratinocytes in wound healing and psoriasis,
      disorders that are also characterized by increased microvascular permeability and
      angiogenesis. In this study, we investigated the expression of VPF/VEGF in three
      bullous diseases with subepidermal blister formation that are characterized by
      hyperpermeable dermal microvessels and pronounced papillary dermal edema. The
      expression of VPF/VEGF mRNA was strongly up-regulated in the lesional epidermis
      of bullous pemphigoid (n = 3), erythema multiforme (n = 3), and dermatitis
      herpetiformis (n = 4) as detected by in situ hybridization. Epidermal labeling
      was particularly intense over blisters, but strong expression was also noted in
      areas of the epidermis adjacent to dermal inflammatory infiltrates at a distance
      from blisters. Moreover, the VPF/VEGF receptors, flt-1 and KDR, were up-regulated
      in endothelial cells in superficial dermal microvessels. High levels of VPF/VEGF
      (138-238 pM) were detected in blister fluids obtained from five patients with
      bullous pemphigoid. Addition of blister fluid to human dermal microvascular
      endothelial cells exerted a dose-dependent mitogenic effect that was suppressed
      after depletion of VPF/VEGF by immunoadsorption. These findings strongly suggest
      that VPF/VEGF plays an important role in the induction of increased microvascular
      permeability in bullous diseases, leading to papillary edema and fibrin
      deposition and contributing to the bulla formation characteristic of these
      disorders.

PMID- 7738352
TI  - Increased types I and III collagen and transforming growth factor-beta 1 mRNA and
      protein in hypertrophic burn scar.
AB  - Hypertrophic scar is the result of abnormal healing that often follows thermal
      injury. Hypertrophic scar is characterized by excessive dermal fibrosis and
      scarring. Five cases of human hypertrophic scar were compared with normal skin
      using in situ hybridization to localize mRNAs for procollagen types I and III and
      transforming growth factor-beta 1. Expression of type I procollagen and TGF-beta
      1 were also examined with immunohistochemistry. The results demonstrated a
      significant increase in the expression of mRNA for types I and III procollagen
      and type I procollagen protein by fibroblasts in hypertrophic scar compared with
      normal skin. In all cases of hypertrophic scar, significant numbers of cells
      expressed TGF-beta 1 mRNA or peptide. Neither TGF-beta 1 mRNA nor protein was
      detected in control tissues. These results suggest a profound increase in
      production and expression of types I and III collagen mRNA by the fibroblasts in
      hypertrophic scar. This may result from increased TGF-beta 1 production, through
      paracrine and autocrine pathways, as have been described for this fibrogenic
      cytokine.

PMID- 7738353
TI  - Reduced growth factor requirements and accelerated cell-cycle kinetics in adult
      human melanocytes transformed with SV40 large T antigen.
AB  - Melanomas develop with high frequency in transgenic mice in which oncogenic
      sequences of the SV40 DNA tumor virus have been specifically targeted to
      melanocytes. To investigate the role of SV40 in melanomagenesis, cultured human
      melanocytes were transformed with a retroviral shuttle vector encoding the SV40
      large T antigen and examined for changes in cell-cycle kinetics and growth-factor
      dependence. Colonies expressing the viral oncogene were morphologically
      indistinguishable from their non-T-antigen-transformed counterparts. Also like
      normal melanocytes, the infected cells remained anchorage dependent and non
      tumorigenic in nude mice. However, T-antigen-positive cultures exhibited
      significantly accelerated population doubling times, increased saturation
      densities with highly confluent monolayers and a three- to fourfold extended life
      span. Most interestingly, cell-cycle analysis revealed a measurable shift from
      quiescent to cycling cells in T-antigen-expressing cultures and an acquired
      ability to progress more rapidly through G1. Moreover, T-antigen-positive
      melanocytes proliferated in the absence of PMA and required markedly reduced
      levels of exogenous bFGF. These studies indicate that the viral oncogen of simian
      virus 40 provides melanocytes with distinct growth advantages that may render
      these cells unusually susceptible to additional environmental challenges
      necessary for full expression of the malignant phenotype.

PMID- 7738354
TI  - Cations inhibit specifically type I 5 alpha-reductase found in human skin.
AB  - Steroid 5 alpha-reductase catalyzes the reduction of testosterone into the very
      potent androgen dihydrotestosterone. Previously, we showed that human type I 5
      alpha-reductase is expressed mainly in the skin, whereas a type II 5 alpha
      reductase is more specifically expressed in the prostate. To assess the possible
      differential effects of various cations on the two types of 5 alpha-reductase, we
      constructed expression vectors and transfected them into SW-13 cells, a human
      adrenal carcinoma cell line containing negligible endogenous 5 alpha-reductase
      activity. The expressed 5 alpha-reductases were analyzed for their sensitivity to
      Li, Ca, Cd, Cu, Mg, Mn, Ni, Zn, and Fe. The results showed that type I 5 alpha
      reductase was strongly inhibited by Cd, Cu, and Zn and moderately inhibited by Ni
      and Fe, with 50% inhibitory concentration values of 0.9, 1.9, 2.0, 169.2, and
      174.3 microM, respectively. In contrast, type II 5 alpha-reductase activity was
      inhibited only by Cu, with a 50% inhibitory concentration value of 19.2 microM.
      The data showed that cations could specifically control 5 alpha-reductase
      activity expression, which is more strongly inhibited in a target tissue,
      especially the skin.

PMID- 7738355
TI  - Retinoic acid receptor gamma mediates topical retinoid efficacy and irritation in
      animal models.
AB  - Among retinoic acid receptors (RARs) alpha, beta, and gamma, the messenger RNA
      level of RAR-gamma is the most readily detectable by Northern blotting in human
      and mouse skin. This observation suggests that RAR-gamma may play a critical role
      in the modulation of the therapeutic benefits and side effects of retinoids in
      skin. To test this hypothesis, 11 RAR-gamma selective retinoids were synthesized
      based on three related structures. Each compound was found to prefer RAR-gamma
      when assessed by retinoid-induced transcriptional activity (RAR-gamma > RAR-beta
      > RAR-alpha). The apparent Kd for binding to recombinant receptor protein was
      found to follow a similar trend. To correlate this receptor selectivity with in
      vivo activity, the compounds were tested topically in the Rhino mouse utriculi
      reduction and rabbit irritation models, two assays widely used to screen
      retinoids for efficacy and side effects, respectively. The results indicated that
      for these compounds, both efficacy in the utriculi reduction assay and irritation
      potential in rabbits correlated positively with the RAR-gamma transactivation
      activity, with r2 of 0.9 and 0.8, respectively. These data suggest that RAR-gamma
      is an important regulator of retinoic acid efficacy in skin and further, that the
      irritation associated with the use of retinoids is most likely a receptor
      mediated process.

PMID- 7738356
TI  - Characteristic cytokines generated by keratinocytes and mononuclear infiltrates
      in oral lichen planus.
AB  - Cytokine production was investigated in oral keratinocytes and tissue-infiltrated
      mononuclear cells (TIMC) obtained from patients with oral lichen planus (OLP).
      The numbers of cells producing interleukin (IL)-1 beta, IL-4, IL-6, granulocyte
      colony-stimulating factor, and tumor necrosis factor-alpha per 10(4) cells in
      keratinocytes from patients with OLP were determined by enzyme-linked immunospot
      assay. These levels were two to threefold greater than those in keratinocytes
      from chronically inflamed gingiva and 10 to 20-fold of those from the intact
      gingiva. The concentrations of these cytokines in the culture supernatants of
      keratinocytes were correlated with the number of cytokine-producing cells.
      Compared with TIMC in the gingiva and peripheral blood mononuclear cells, TIMC in
      OLP were more cytokine-productive, with larger numbers of cytokine-producing
      cells that expressed more cytokine messengers. More IL-6, IL-2, and IL-10 were
      generated from TIMC in OLP, whereas less granulocyte colony-stimulating factor
      was generated. After pretreatment with IL-2, TIMC from OLP patients generated
      more IL-6 than did peripheral blood mononuclear cells, and IL-4-pretreated TIMC
      from the patients released larger amounts of IL-2, IL-6, and IL-10. These results
      indicate that keratinocytes play a critical role in OLP through production of
      large amounts of cytokines, that TIMC are stimulated in situ and differentiated
      to produce cytokines characteristic of OLP, and that the inflammatory condition
      of OLP is determined by the local cytokine network.

PMID- 7738357
TI  - Interleukin-8 and GRO alpha prime human neutrophils for superoxide anion
      production and induce up-regulation of N-formyl peptide receptors.
AB  - Interleukin-8 (IL-8) and GRO alpha are leukocyte-attracting peptides of the
      chemokine family. To study the priming potential of these chemokines, we measured
      superoxide anion production and up-regulation of N-formyl peptide receptors in
      human neutrophils. IL-8 and GRO alpha themselves did not stimulate production of
      significant amounts of superoxide anions but potentiated N-formyl peptide-induced
      superoxide anion production in a concentration-dependent manner. Binding
      measurements by flow cytometry at 37 degrees C with fluorescein-labeled N-formyl
      peptide revealed enhanced total N-formyl peptide binding after pretreatment of
      neutrophils with IL-8 and GRO alpha. Binding measurements performed at 4 degrees
      C indicated that the chemokines stimulated the up-regulation of N-formyl peptide
      receptors at the cell surface but did not alter their affinity for the ligand.
      This study indicates that IL-8 and GRO alpha, in addition to their known
      chemotactic activity, prime neutrophils for superoxide anion production,
      presumably by up-regulating the number of receptors for strong superoxide-anion
      triggering stimuli.

PMID- 7738358
TI  - Glutathione plays a key role in the depigmenting and melanocytotoxic action of N
      acetyl-4-S-cysteaminylphenol in black and yellow hair follicles.
AB  - This study examined the effect of glutathione on the in vivo depigmenting potency
      of N-acetyl-4-S-cysteaminylphenol (N-acetyl-4-S-CAP) in black and yellow mice
      after multiple intraperitoneal injections on 10 consecutive days. In black mice
      (C57BL/6J, a/a), N-acetyl-4-S-CAP showed dose-dependent depigmenting potency
      (0.5, 1.0, and 2.0 mmol/kg), which was in parallel to the tissue eumelanin
      content (98%, 28%, and 3% of controls, respectively) and to the tissue
      glutathione content (94%, 85%, and 76%, respectively). In lethal yellow mice
      (C57BL/6J, Ay/a), only a dose of 2.0 mmol/kg showed the color change of hair to
      dark, not to white as seen in black mice. This was reflected by the decrease of
      pheomelanin content (56%) and the increase of eumelanin content (28% of black
      mice). The simultaneous administration of N-acetyl-cysteine, which up-regulated
      glutathione content, completely abolished the depigmenting potency of N-acetyl-4
      S-CAP, whereas administration of buthionine sulfoximine, which depleted the
      tissue glutathione content, enhanced the depigmenting potency of N-acetyl-4-S-CAP
      in black hair. In yellow mice, the darkening of hair follicles by 2.0 mmol/kg of
      N-acetyl-4-S-CAP was completely abolished by the combined administration of N
      acetyl-cysteine, with the resulting hair color the same as in controls, whereas
      combined administration with buthionine sulfoximine caused some whitening of
      yellow hair follicles. Our data indicate that the tissue content of glutathione
      regulates melanocytotoxicity and depigmenting potency of N-acetyl-4-S-CAP and
      that this alteration of glutathione content may switch the melanogenesis type
      from pheomelanin to eumelanin.

PMID- 7738359
TI  - Epidermal damage and limited coagulation depth with the flashlamp-pumped pulsed
      dye laser: a histochemical study.
AB  - To investigate vessel coagulation depth and tissue damage in therapy with the
      flashlamp-pumped pulsed dye laser (585 nm, 5 mm spot size, 450 microsecond pulse
      duration, 6-8 J/cm2), we used the nitroblue-tetrazolium chloride stain in 22 post
      treatment biopsy specimens from patients with port wine stain. With this method,
      thermally damaged tissue can be easily differentiated from unchanged tissue to
      the level of single cells. The results showed that in superficial port wine stain
      vessels up to 150 microns in diameter, vessel coagulation was complete and
      selective without further dermal damage. With the increase of vessel diameter,
      strong superficial hemoglobin absorption led to only partial vessel-wall
      coagulation and, in some cases, to superficial dermal damage. Likewise, deeper
      vessels were not coagulated because of shadow effects by superficial vessel
      layers. Thus, the overall vessel-wall coagulation depth of the flashlamp-pumped
      dye laser was limited to a maximum of 0.65 mm (mean 0.37 mm). In addition, some
      degree of epidermal damage was present in most specimens, which significantly
      increased with epidermal melanin content and resulted in epidermal coagulation
      and blistering in pigmented skin. Our results explain the occurrence of crusting,
      hyperpigmentation, and hypopigmentation in therapy with the flashlamp-pumped dye
      laser and its limited effect on dark or hypertrophic port wine stains in adults
      featuring large vessel diameters or multiple vessel layers.

PMID- 7738360
TI  - Genetic linkage between the collagen type VII gene COL7A1 and pretibial
      epidermolysis bullosa with lichenoid features.
AB  - Pretibial epidermolysis bullosa is a rare form of dominant dystrophic
      epidermolysis bullosa. The disease was diagnosed after considerable delay in a
      large Belgian family and was remarkable for its late age at onset and its
      misleading clinical presentation in the proband, which strongly resembled
      keratosis lichenoides chronica. Both recessively and dominantly inherited forms
      of dystrophic epidermolysis bullosa have been shown to be linked to the collagen
      type VII gene, COL7A1. Two-point linkage analysis with two intragenic
      polymorphisms (PvuII, AluI) in COL7A1 was performed. Strong genetic linkage
      between the disease in this family and COL7A1 was demonstrated by a lod score of
      4.45 (theta = 0) for the AluI polymorphism. The observed intrafamilial
      variability of clinical phenotypes contradicts the presently proposed
      classification of dominantly inherited dystrophic epidermolysis bullosa.

PMID- 7738361
TI  - Inhibition of interferon-gamma-induced intercellular adhesion molecule-1
      expression on human keratinocytes by phosphorothioate antisense
      oligodeoxynucleotides is the consequence of antisense-specific and antisense-non
      specific effects.
AB  - Expression of intercellular adhesion molecule-1 (ICAM-1) by keratinocytes is an
      important event in the pathogenesis of T-cell-mediated inflammatory skin
      diseases. To determine if ICAM-1 expression could be selectively modulated, two
      antisense phosphorothioate oligonucleotides (S-ODN) targeting the translation
      initiation and 3' untranslated regions of ICAM-1 mRNA were added as lipid
      complexes to cultures of keratinocytes. Interferon-gamma was added after 24 h to
      induce ICAM-1 expression, which was quantitated by flow cytometry after 48 h. The
      S-ODN targeting the translation initiation site did not inhibit ICAM-1 expression
      at 0.2-20.0 microM. In contrast, 0.2-1.0 microM of the S-ODN targeting a site in
      the 3' untranslated region abrogated ICAM-1 expression in up to 75% of the
      keratinocytes; this inhibition was reversible when complementary sense S-ODN was
      added. Phosphodiester ODN (PD-ODN) targeting the same sites did not inhibit ICAM
      1 expression on keratinocytes, most likely as a consequence of rapid degradation.
      Inhibition of ICAM-1 by the antisense S-ODN was selective; expression of beta 2
      microglobulin, alpha 3-integrin, and beta 1-integrin remained largely unaffected
      and interferon-gamma-induced HLA-DR expression was inhibited to a much lesser
      extent than ICAM-1. Antisense-non-specific inhibition was also noted in that two
      scrambled S-ODN with an identical nucleotide (14 of 20 cytosines) composition
      inhibited ICAM-1 expression in up to 44% of the keratinocytes, whereas a
      degenerate S-ODN did not. The data demonstrate the complex effects exerted by
      antisense S-ODN in that ICAM-1 expression was inhibited via antisense-non
      specific mechanisms probably due to the intrinsic properties of the S-ODN as well
      as via the anticipated sequence-specific mechanisms.

PMID- 7738362
TI  - Pentoxifylline inhibits tumor necrosis factor-alpha (TNF alpha)-induced T
      lymphoma cell adhesion to endothelioma cells.
AB  - Pentoxifylline, a methylxanthine derivative, has been shown to inhibit T-cell
      mediated cutaneous immune response by yet ill-understood mechanisms. Because cell
      adhesion to endothelial cells is a critical step in the initiation of such immune
      responses, we analyzed whether pentoxifylline would affect this process. To
      address this issue, adhesion of mouse T-lymphoma cells (TK-1) to mouse
      endothelioma cells (eEnd.2), either untreated or stimulated with tumor necrosis
      factor-alpha (TNF alpha), was studied. Pentoxifylline reduced the ability of
      endothelioma cells stimulated with different concentrations of TNF alpha, but not
      of untreated endothelioma cells, to bind T-lymphoma cells in dose-dependent (10(
      5)-10(-3) M) fashion. Selective incubation of either endothelioma cells or T
      lymphoma cells revealed that pentoxifylline acted exclusively on the endothelioma
      cells, even when added after TNF alpha stimulation. We questioned whether
      pentoxifylline suppressed T-lymphoma cell/endothelioma cell interactions by
      interfering with adhesion molecules expressed by either cell. However, as
      determined by flow cytometry, pentoxifylline did not alter TNF alpha-induced
      upregulation of intercellular adhesion molecule-1 or vascular cellular adhesion
      molecule-1 on endothelioma cells nor did it affect constitutive CD11a, CD18, or
      alpha 4-integrin expression on T-lymphoma cells, suggesting that rather than
      affecting quantitative expression of these adhesion molecules, pentoxifylline
      might modulate their avidity. We conclude that pentoxifylline in therapeutically
      achievable concentrations is a potent inhibitor of TNF alpha-induced T-lymphoma
      cell adhesion to endothelioma cells. This finding may account, at least in part,
      for the recently discovered anti-inflammatory action of pentoxifylline.

PMID- 7738364
TI  - Involvement of phospholipase D in ganglioside GQ1b-induced biphasic
      diacylglycerol production in human keratinocytes.
AB  - Ganglioside IV3 (NeuAc)2, II3 (NeuAc)2-GgOse4Cer (GQ1b), which induces terminal
      differentiation in keratinocytes, was previously found to enhance the mass
      content of inositol 1,4,5-trisphosphate and intracellular calcium concentration
      ([Ca++]i), peaking at 30 seconds. In the present study, the biphasic accumulation
      of 1,2 diacylglycerol, i.e., the first transient and the second sustained phase,
      was observed in cultured human keratinocytes stimulated by GQ1b. On the other
      hand, II3 NeuAc-LacCer (GM3), which inhibits keratinocyte proliferation without
      inducing differentiation, did not cause diacylglycerol formation.
      Phosphatidylethanol, produced by transphosphatidylation and a potential marker
      for phospholipase D activity, was produced by the exposure to GQ1b in the
      presence of ethanol. The second sustained phase of diacylglycerol was repressed
      by ethanol, indicating that the diacylglycerol-formation pathway via
      phospholipase D followed by phosphatidic acid phosphohydrolase would in part
      account for the second diacylglycerol phase. Furthermore, this second phase of
      GQ1b-induced diacylglycerol generation was reduced by pretreatment with
      propranolol, an inhibitor of phosphatidic acid phosphohydrolase. In addition, the
      levels of [3H]choline, a direct metabolite of the phospholipase D pathway, were
      elevated within 1 min after GQ1b addition and then sustained for at least 20 min.
      Taken together, the results suggest that the phospholipase D pathway may
      contribute to the second phase of diacylglycerol formation, which might be
      involved in differentiation.

PMID- 7738363
TI  - Characterization of paraneoplastic pemphigus autoantigens by immunoblot analysis.
AB  - We investigated the antigen molecules for six clinically typical cases of
      paraneoplastic pemphigus (PNP) using immunofluorescence, immunoprecipitation, and
      immunoblotting. All the PNP sera showed a clear reactivity with transitional
      epithelia of rat urinary bladder and immunoprecipitated the 250-kD, 230-kD, 210
      kD, 190-kD, and 170-kD proteins in various combinations, confirming the diagnosis
      of PNP. Immunoblot analysis demonstrated slightly different reactivity from that
      of immunoprecipitation. With immunoblotting of normal human epidermal extract,
      bovine desmosome preparation, and extract of cultured squamous cell carcinoma
      cells, all the PNP sera reacted with a characteristic doublet of the 210-kD and
      190-kD proteins. However, immunoblotting detected the 250-kD desmoplakin I and
      the 230-kD bullous pemphigoid antigen less frequently and did not detect the 170
      kD protein. Further immunoblot studies indicated that the 210-kD protein is
      different from desmoplakin II and that the 190-kD protein is most frequently
      detected by PNP sera. Two of the six PNP sera specifically reacted with the
      extracellular domain of recombinant pemphigus vulgaris antigen protein,
      indicating that pemphigus vulgaris antigen may be involved in PNP. In future
      studies to unravel the complex mechanisms of the PNP antigens, the immunoblot
      technique may be a useful tool.

PMID- 7738365
TI  - Microdialysis in cutaneous pharmacology: kinetic analysis of transdermally
      delivered nicotine.
AB  - Direct measurements of cutaneous drug levels and kinetics have long been hampered
      by lack of appropriate methods. Recently, studies have indicated that
      microdialysis, a method of continuous in vivo sampling of extracellular fluid,
      may also be performed in human skin. The present study was designed to evaluate
      this technique for kinetic analyses of cutaneous drug levels. Using a transdermal
      nicotine delivery system with 35 mg of nicotine as a model, nicotine levels were
      determined in the dialysate of human skin by means of high performance liquid
      chromatography. In vitro studies demonstrated that nicotine levels in the
      dialysate strictly correlated with nicotine concentrations in the dialyzed
      medium. In nine healthy male volunteers receiving nicotine by transdermal
      delivery, nicotine was detectable within 90-180 min, and peak levels of
      approximately 1000 ng/ml were detected within 240-360 min of patch application.
      Correlation analyses of the individual data from our subjects revealed that
      nicotine kinetics were independent of skin barrier function, as assessed by
      transepidermal water loss, but indicated that the detectable maximum nicotine
      levels may depend on the location of the probe. In summary, the present study
      demonstrates that microdialysis may be a novel, powerful tool to study cutaneous
      pharmacology in vivo.

PMID- 7738366
TI  - Beta IG-H3, a novel secretory protein inducible by transforming growth factor
      beta, is present in normal skin and promotes the adhesion and spreading of dermal
      fibroblasts in vitro.
AB  - We have previously identified a gene, beta ig-h3, which is highly induced in A549
      cells (human lung adenocarcinoma) after growth arrest by transforming growth
      factor-beta. The beta ig-h3 gene encodes a 683-amino-acid secretory protein
      termed beta IG-H3, and treatment of several cell lines with transforming growth
      factor-beta results in increased secretion of beta IG-H3 into cell culture
      supernatants. In this report, we further characterize beta IG-H3 with respect to
      its synthesis and function. Primary human foreskin fibroblasts grown in monolayer
      culture produced beta IG-H3 mRNA and secreted beta IG-H3 protein into the growth
      media. Treatment of these cells with transforming growth factor-beta led to an
      increase in beta IG-H3 mRNA and protein. Cells grown on three-dimensional
      scaffolds secreted beta IG-H3 into the extracellular matrix, as judged by
      immunostaining with anti-beta IG-H3 antibodies. beta IG-H3 was also detected in
      normal human skin, especially in the papillary dermis. Finally, we show that
      recombinant beta IG-H3 supported attachment and spreading of dermal fibroblasts,
      suggesting that beta IG-H3 may function as an extracellular attachment protein in
      skin.

PMID- 7738367
TI  - Comparative genetic association of human leukocyte antigen class II and tumor
      necrosis factor-alpha with dermatitis herpetiformis.
AB  - Dermatitis herpetiformis is a chronic subepidermal vesicular autoimmune skin
      disease characterized by a strong association with the human leukocyte antigen A1
      B8-DR3-DQ2 haplotype. Although the strongest major histocompatibility complex
      association has been shown to be with the DQw2 (DQB1*0201/DQA1*0501) heterodimer,
      recent evidence has suggested that there may be up to three susceptibility loci
      within the major histocompatibility complex. Tumor necrosis factor-alpha (TNF
      alpha) is a cytokine with a broad range of proinflammatory, immunomodulating, and
      catabolic activities. We have recently described the first known polymorphism in
      the human TNF-alpha gene, which is biallelic and lies in the promoter region. The
      rare allele, TNF2, is in strong linkage disequilibrium with the human leukocyte
      antigen A1-B8-DR3-DQ2 haplotype. We therefore examined TNF-alpha genotypes in
      patients with dermatitis herpetiformis and controls and compared the association
      with that of the class II alleles. Although TNF2 is strongly associated with
      dermatitis herpetiformis, this was weaker than the association with the class II
      loci, with DQw2 (DQB1*0201/DQA1*0501) showing the strongest disease association.
      Of the four patients negative for this marker, only one carried the TNF2 allele.
      These results indicate that TNF2 is not a major disease susceptibility marker,
      although our results do not exclude a minor role.

PMID- 7738368
TI  - Keratinocytes and fibroblasts in a human skin equivalent model enhance melanocyte
      survival and melanin synthesis after ultraviolet irradiation.
AB  - To investigate paracrine effects of fibroblasts and keratinocytes on melanocyte
      behavior after ultraviolet (UV) irradiation, we compared an in vitro skin
      equivalent model with melanocyte cultures. Human melanocytes were maintained
      alone in monolayer cultures or on dermal equivalents with or without
      keratinocytes and were irradiated daily with solar-simulated light. After seven
      daily UV irradiations, monolayer melanocytes displayed dose-dependent increases
      in cellular damage. In contrast, melanocytes on dermal equivalents survived
      strikingly better. Moreover, UV-irradiated skin equivalent melanocytes became
      highly dendritic as compared with sham-irradiated cells, closely mimicking their
      morphology in UV-irradiated skin. In addition, in skin equivalents melanocytes
      migrated from the center to the periphery of the keratinocyte layer after UV
      irradiation. Melanin production per culture, as measured by 14C
      dihydroxyphenylalanine incorporation, was consistently higher in skin equivalent
      melanocytes than in monolayer melanocytes from the same donor, and it was highest
      in melanocytes from skin equivalents containing both keratinocytes and
      fibroblasts. Our data strongly suggest that fibroblasts and keratinocytes
      modulate melanocyte function in skin. The skin equivalent is a valuable model for
      investigating paracrine effects on melanocytes after UV irradiation.

PMID- 7738369
TI  - Ras gene mutations: a rare event in nonmetastatic primary malignant melanoma.
AB  - Ras gene mutations have been implicated in the pathogenesis of a variety of human
      tumors. Mutated ras genes have been isolated from human melanoma cell lines, but
      subsequent studies indicated that ras gene mutations may be a rare event in
      melanocytic lesions. Recently, a study reported a high frequency of ras mutations
      correlated with increasing invasion level. To address this inconsistency in the
      published data, we analyzed 50 primary melanomas to correlate invasion level,
      tumor thickness, histologic typing, and body localization with point mutations
      around codons 12/13/61 of the three ras genes. After micro-dissection of paraffin
      embedded tumor tissue, ras gene mutations were analyzed by direct sequencing of
      tumor DNA amplified by polymerase chain reaction. Only two melanomas exhibited
      ras gene mutations, one sample containing a transition from A to G at position 2
      of N-ras codon 61 and the other exhibiting a transversion from C to A at position
      1 and a transition from A to G at position 2 of N-ras codon 61. Both tumors were
      classified as Clark level IV, with a tumor thickness of 2.5 and 1.2 mm,
      respectively. Both were typed as superficial spreading melanoma and localized to
      intermittently sun-exposed body sites. The low frequency of ras mutations in
      malignant melanoma and the lack of ras mutations in melanoma samples from
      constantly sun-exposed body sites argue against the hypothesis of ras mutations
      as a marker of progression in malignant melanoma and the suggestion that ras
      mutations occur predominantly in melanomas from constantly sun-exposed body
      sites.

PMID- 7738371
TI  - 2nd International Research Workshop on Alopecia Areata. Bethesda, Maryland,
      November 7-8, 1994.

PMID- 7738370
TI  - Combined Photomedicine Society/American Society for Photobiology meeting June 28,
      1994, Scottsdale, Arizona.

PMID- 7738372
TI  - Abnormalities in the ultrastructure of melanocytes and the outer root sheath of
      clinically normal hair follicles from alopecia areata scalps.

PMID- 7738373
TI  - Immunity to hair follicles in alopecia areata.

PMID- 7738374
TI  - An allele of the interleukin-1 receptor antagonist as a genetic severity factor
      in alopecia areata.

PMID- 7738375
TI  - C3H/HeJ mouse model for alopecia areata.

PMID- 7738376
TI  - Fibroblast growth factor and the hair cycle of the hairless mouse.

PMID- 7738377
TI  - Loss of vascular endothelial growth factor in human alopecia hair follicles.

PMID- 7738379
TI  - T-cell receptor repertoire V beta in alopecia areata.

PMID- 7738378
TI  - Factors mediating the interactions between epidermal and dermal cells in skin
      grafts that might be important for hair follicle development.

PMID- 7738380
TI  - No cell-surface-reactive antibodies against cultured autologous melanocytes found
      in alopecia areata sera.

PMID- 7738381
TI  - Role of the thymus gland in alopecia areata.

PMID- 7738382
TI  - Histopathology of alopecia areata in horizontal sections of scalp biopsies.

PMID- 7738383
TI  - Is trachyonychia, a variety of alopecia areata, limited to the nails?

PMID- 7738384
TI  - A molecular approach to alopecia areata.

PMID- 7738385
TI  - Glucocorticoid regulation of hair growth in alopecia areata.

PMID- 7738386
TI  - Defects of pelage hairs in 20 mouse mutations.

PMID- 7738387
TI  - Alopecia areata in humans and other mammalian species.

PMID- 7738388
TI  - Hair follicle autoantibodies in DEBR rat sera.

PMID- 7738389
TI  - Topical immunotherapy in children with alopecia areata.

PMID- 7738391
TI  - Hair follicle stem cells: present concepts.

PMID- 7738390
TI  - Treatment of severe alopecia areata with topical diphenylcyclopropenone and 5%
      minoxidil: a clinical and immunopathologic evaluation.

PMID- 7738392
TI  - Hair follicle and fiber reconstruction.

PMID- 7738393
TI  - HLA class II alleles in long-standing alopecia totalis/alopecia universalis and
      long-standing patchy alopecia areata differentiate these two clinical groups.

PMID- 7738394
TI  - Proteoglycans and associated proteins of the mammalian hair follicle.

PMID- 7738395
TI  - Hair follicle development and hair growth from defined cell populations grafted
      onto nude mice.

PMID- 7738396
TI  - Cultured human hair follicles and growth factors.

PMID- 7738397
TI  - Analysis of HLA-D locus alleles in alopecia areata patients and families.

PMID- 7738398
TI  - Is the dermal papilla a primary target in alopecia areata?

PMID- 7738399
TI  - Immunologic cytotoxicity in alopecia areata: apoptosis of dermal papilla cells in
      alopecia areata.

PMID- 7738400
TI  - Cytokines and dermal papilla function in alopecia areata.

PMID- 7738401
TI  - [The 92nd Symposium of the Japanese Society of Internal Medicine. Nagoya City,
      April 4-6, 1995. Abstracts].

PMID- 7738402
TI  - Role of charge in the radioprotection of E. coli by thiols.
AB  - The role of net charge (zeta) of thiols in their ability to radioprotect cells
      has been investigated in a glutathione (GSH)-deficient strain of E. coli. This
      strain, 7, is deficient in the enzyme gamma-glutamylcysteine synthetase and
      allows the effects of added low molecular weight thiols to be studied. Using the
      gas explosion system it is possible to measure the chemical repair of the free
      radical precursors of lethal lesions by thiols in intact cells. The first-order
      chemical repair rate in strain 7 is 280 s-1 in comparison with 1100 s-1 in the
      wild-type strain 1157. From the measured difference in the intracellular
      concentration of GSH between the wild-type and the mutant, this gives a second
      order repair rate, kr, of 1.23 +/- 0.3 x 10(5) dm3mol-1s-1. Measurement of
      intracellular thiol levels after addition of various low molecular weight thiols
      showed that uptake was rapid, leading to stable thiol levels within 1 min. The
      ratios of the intracellular to extracellular concentrations (Cin/Cout) were 0.74
      for 3-mercaptopropionic acid (zeta = -1), 0.56 for 2-mercaptoethanol (zeta = 0),
      1.47 for cysteamine (zeta = +1) and 1.04 for WR1065 (zeta = +2). The kr's for
      these thiols were 1.3 +/- 0.5 x 10(5) dm3mol-1s-1 for 30-mercaptopropionic acid,
      3.3 +/- 1.6 x 10(5) dm3mol-1s-1 for 2-mercaptoethanol, 3.9 +/- 1.1 x 10(5) dm3mol
      1s-1 for cysteamine and 2.7 +/- 1.1 x 10(6) dm3mol-1s-1 for WR1065. These are
      lower and increase less with charge than previously published values for chemical
      repair in isolated pBR322 DNA, probably because of the association of
      nucleoproteins and polyamines with the cellular DNA of E. coli. However, the
      approximate three-fold increase in kr per unit increase in zeta shows that the
      counter-ion condensation and co-ion depletion are important in determining the
      effectiveness of charged thiols in the radioprotection of E. coli.

PMID- 7738403
TI  - Inhibition of radiation-induced changes of glyoxalase I activity in mouse spleen
      and liver by phenothiazines.
AB  - Swiss albino mice (male) were irradiated with gamma-rays at a dose-rate of 0.05
      Gy s-1, and the activities of glyoxalase I (GI) and glyoxalase II (GII) were
      determined after 24 h in the spleen and liver. Radiation up to 4 Gy increased the
      activity of GI and decreased that of GII. It was possible that the radiation
      induced changes in the activity of the glyoxalase system, particularly that of
      GI, were suggestive of the regeneration status of the tissue. Phenothiazines such
      as chlorpromazine (CPZ), promethazine (PMZ) and trimeprazine (TMZ) inhibited the
      radiation-enhanced activity of GI in a concentration-dependent manner. On the
      other hand, almost no change in the activity of GII was observed using
      phenothiazines. The effect of phenothiazines on radiation-induced changes of
      glyoxalase activity were reversed in the presence of ferrous (Fe2+) ions.
      However, phenothiazines inhibited the radiation effect in the presence of ferric
      (Fe3+) ions. This combined effect was predominant in the liver. A possible
      mechanism for the modifying effect of phenothiazines is suggested.

PMID- 7738404
TI  - UV radiation protecting efficacy of cysteine derivatives, studies with UVA
      induced binding of 8-MOP and CPZ to rat epidermal biomacromolecules in vivo.
AB  - With the aim of optimizing the UV radiation protecting efficacy of N
      acetylcysteine (NAC), the following topically applied cysteine derivatives were
      investigated: N-acetylcysteine ethylester (NACET), S-acetylcysteine ethylester
      (SACET), cysteine ethylester (CYSET), N,S-diacetylcysteinamide (SNACA), N,S
      diacetylcysteine (SNAC) and N,S-diacetylcysteine ethylester (SNACET). As a
      measure for protection the inhibition of in vivo irreversible photobinding of the
      labelled phototoxic drugs chlorpromazine (CPZ) and 8-methoxypsoralen (8-MOP) to
      rat epidermal biomacromolecules was used. The duration of protection of the
      cysteine derivatives was shortened by S-acetylation, N-acetylation and carboxyl
      derivatization. Compounds with a free thiol group showed a long-lasting presence
      in the stratum corneum, probably by the formation of mixed disulphides with
      proteins. The intrinsic protecting efficacy with respect to the total epidermis
      increased in the order CYSET < SNACET,SNACA,SACET < NACET, SNAC,NAC. The results
      of this study are discussed in view of susceptibility to oxidation, epidermal
      bioavailability and metabolic activation. With respect to the viable epidermis we
      postulate that NACET and SNAC have the most promising properties as UV protective
      agents.

PMID- 7738405
TI  - Mutant frequency at the H-2K class 1 and HPRT genes in T lymphocytes from the X
      ray-exposed mouse.
AB  - The frequency of H-2Kk and HPRT-deficient T cells was measured in the H-2Kb,
      kDd,k genotype mouse 8-10 weeks after X-ray exposure at doses up to 6 Gy to
      compare the mutant frequency (MF) of an autosomal gene with that of an X
      chromosomal gene. H-2K mutants were enriched by magnetic cell separation (MACS)
      using the H-2Kk-specific monoclonal antibody H100.5/28 and were isolated by
      limiting dilution cloning. Finally, the mutant phenotype was verified by flow
      cytometric analysis in a representative number of clones. The frequency of HPRT
      deficient T cells rises from 2.5 x 10(-6) at 0 Gy to a maximum of 1.13 x 10(-4)
      at 4 Gy, and decreases to 2.9 x 10(-5) at 6 Gy. The H-2K- MF in the non
      irradiated mouse was 8.4 x 10(-7). It increases with dose to a maximum of 8.1 x
      10(-6) at 4 Gy and declines to 3.3 x 10(-6) at 6 Gy. The H-2K- MF measured
      depends on the monoclonal antibody used for the isolation of mutants. In a pilot
      study with another H-2Kk-specific monoclonal antibody (11.4.1), the spontaneous
      MF was four times higher than in experiments with the H100.5/28 monoclonal
      antibody. The expression of other class 1 antigens was investigated in H-2K-
      clones. The H-2Dd antigen had also disappeared in six of 41 clones from
      irradiated animals. This gene is situated at a distance of 1500 kb from the K
      locus. The H-2Kb antigen was present in every investigated clone. In the
      discussion a model is presented that explains the shape of the dose-response
      curve of MF by selection against mutants in vivo systems under homeostasis. The
      results of the present investigation indicate that observed X-ray mutagenicity
      depends on many factors and that several genes have to be explored before
      reliable risk estimates are possible.

PMID- 7738406
TI  - Frequencies of complex chromosome exchange aberrations induced by 238Pu alpha
      particles and detected by fluorescence in situ hybridization using single
      chromosome-specific probes.
AB  - We undertook an analysis of chromosome-type exchange aberrations induced by alpha
      particles using fluorescence in situ hybridization (FISH) with whole chromosome
      specific probes for human chromosomes 1 or 4, together with a pan-centromeric
      probe. Contact-inhibited primary human fibroblasts (in G1) were irradiated with
      0.41-1.00 Gy 238Pu alpha-particles and aberrations were analysed at the next
      mitosis following a single chromosome paint. Exchange and aberration painting
      patterns were classified according to Savage and Simpson (1994a). Of exchange
      aberrations, 38-47% were found to be complex derived, i.e. resulting from three
      or more breaks in two or more chromosomes, and the variation with dose was
      minimal. The class of complex aberrations most frequently observed were
      insertions, derived from a minimum of three breaks in two chromosomes. There was
      also an elevated frequency of rings. The high level of complex aberrations
      observed after alpha-particle irradiation indicates that, when chromosome domains
      are traversed by high linear energy transfer alpha-particle tracks, there is an
      enhanced probability of production of multiple localized double-strand breaks
      leading to more complicated interactions.

PMID- 7738407
TI  - Effects of topoisomerase I-targeted drugs on radiation response of L5178Y
      sublines differentially radiation and drug sensitive.
AB  - The murine L5178Y (LY) lymphoma sublines, LY-R (radiation resistant) and LY-S
      (radiation sensitive) display a difference in susceptibility to camptothecin
      (CPT): LY-S cells are less sensitive to killing by this inhibitor of
      topoisomerase I than LY-R cells. Post-treatment (CPT present until 3 h after
      irradiation) sensitizes only LY-S cells. In agreement with this, only in LY-S
      cells is the relative number of DNA-protein cross-links formed after treatment
      with CPT + X higher than expected for additivity of X-ray and CPT-induced damage.
      The pattern of changes in the labelling indices and cell cycle distribution in
      cells that underwent combined treatment is essentially like that seen for single
      agent treatment: for LY-S cells like that for radiation, for LY-R cells like that
      for CPT. We found no direct relation between the patterns of cell cycle
      distributions and the enhancement of the lethal effect of X-irradiation by CPT
      post-treatment. The sublines are not markedly differentially sensitive to beta
      lapachone, which modifies topoisomerase I activity, and not sensitized to X-rays
      by post-irradiation treatment with the drug.

PMID- 7738408
TI  - Inherent cellular differences may explain the dissimilar survival of RIF-1 and
      KHT tumour cells under aerobic and hypoxic conditions.
AB  - Although previous work has shown striking differences in radiobiological hypoxic
      fraction between KHT and RIF-1 murine sarcomas, intravascular oxyhaemoglobin
      (HbO2 saturations have revealed less substantial variations. Using quantitative
      histological techniques, we have also found minor differences in the
      distributions of distances between tumour cells and the nearest bloods vessel for
      KHT versus RIF-1 sarcomas. We report here, the results of an investigation of the
      inherent ability of these tumour cells to withstand conditions of hypoxia by in
      vitro culturing under aerobic and anoxic conditions. Tumours were dissociated,
      seeded into culture dishes, and placed in air-tight aluminium chambers. These
      chambers were repeatedly evacuated and refilled with a mixture of 95% N2 and 5%
      CO2 over a 2.5-h period. Following anoxic exposure, cells were removed and
      replated, and the in vitro plating efficiency (PE) was determined using a colony
      survival assay. After normalizing to aerobic controls, KHT tumour cells had a
      significantly lower PE, following a 16-hour exposure to anoxic conditions (0.4),
      than RIF-1 (0.6). Increasing the hypoxic exposure to 40 h resulted in normalized
      PEs of 0.07 for KHT versus 0.4 for RIF-1. Although these results support the
      hypothesis that the two tumour lines have different inherent abilities to
      withstand hypoxia, they do not explain the failure of direct measures of tumour
      oxygenation to correlate with the radiobiological hypoxic fraction. Additional
      factors such as differences in oxygen diffusivity or oxygen consumption rates
      between tumour lines may also be involved.

PMID- 7738409
TI  - The beta component of human cell survival curves and its relationship with split
      dose recovery.
AB  - In principle, alpha and beta can be obtained from single-dose survival curves
      using standard linear-quadratic fitting; however, alpha and beta being
      interdependent, it is difficult to evaluate them together with good precision. On
      the assumption that full recovery from a split-dose treatment gives a result that
      is the product of the single-dose surviving fraction, it has been suggested that
      the measurement of split-dose recovery should provide a method to measure beta
      alone using the formula: beta RR = lnRR/2d2. Most of the studies published to
      date have been carried out on cancer cell lines or transformed normal cells. We
      have systematically tested the above proposal on two normal human fibroblast cell
      lines (HF19 and 1BR3) in two different situations: growing cells, and plateau
      phase cells. Two different protocols were used to assess both the potential
      influence of a priming dose on the surviving cells and the extent of the split
      dose recovery. The survival curves generated after different priming doses did
      not show any significant change in comparison with those achieved without
      previous irradiation. In addition, the split-dose survival was not different from
      the square of the corresponding single-dose survival (model free). In these
      conditions, beta RR's obtained by a linear regression of the recovery ratio data
      were very similar to the beta's obtained by single doses. However, a curvilinear
      regression (with a very small negative term at high doses) appears to be more
      appropriate for cells in plateau phase. This has the result that, as the dose
      increases, the cell survival curves tend to become less bending than would be
      expected from the linear-quadratic model; however, the linear-quadratic fitting
      is still a reasonable characterization of the radiation response since the in
      vitro colony formation method does not allow measurement of survival < 10(-4).

PMID- 7738410
TI  - Rapid communication: effect of irradiation on lymphocyte proliferation and
      differentiation: potential of IL-6 in augmenting antibody responses in cultures
      of murine spleen cells.
AB  - Ionizing radiation induces both quantitative and qualitative changes in the
      lymphoid cells of both man and experimental animals, including inhibition of
      antibody responses. However, the cellular basis of this immunological lesion is
      not clear. In the present study, groups of mice were exposed to 2.0 Gy gamma-rays
      or sham irradiated, and 2 days later animals were killed and spleen cells were
      cultured with TNP-Ficoll and assayed for antibody responses. Results indicated a
      significant decrease in the number of anti-TNP, plaque-forming cells in cultures
      from the irradiated mice compared with cultures from the control. When
      lymphocytes were stimulated in vitro with anti-IgM or anti-CD3, there was a
      decreased proliferation in spleen cell cultures derived from the irradiated mice
      compared with those from the control. Since radiation treatment was found to
      deplete both T and B cells in equal proportions in spleen and an equal number of
      both control or treated cells were used in culture, the immunological
      abnormalities may have been due to intrinsic defects in irradiated cells.
      Addition of IL-6 to irradiated spleen cell cultures was able to augment anti-TNP,
      plaque-forming cell responses indicating the possibility that in the future this
      cytokine can be used in vivo to induce protection from infectious diseases in
      irradiated individuals.

PMID- 7738411
TI  - Immune functions of spleen lymphocytes of rats subjected to chronic irradiation
      and antioxidant (ubiquinone Q-9) diet.
AB  - The dynamics of T and B cell immunity in spleens from rat exposed to whole-body
      chronic irradiation with dose rates of 12.9 cGy/day (range 1-10 Gy) and 3.0
      cGy/day (range 0.57-2.04 Gy) were investigated. gamma-irradiation with a dose
      rate of 12.9 cGy/day was shown to produce a wave-like suppression of the T
      lymphocyte mitogenic response. Irradiation with a dose-rate of 3.0 cGy/day caused
      a decrease in immune response of T lymphocytes 48 days after onset of exposure
      (total dose 1.4 Gy). It was also shown that chronic irradiation with a dose-rate
      of 3.0 cGy/day produced significant changes in the DNA of T lymphocytes. Our
      results show that the radiation-induced suppression of immune functions and
      damage to DNA structure were partially eliminated when animals were fed a daily
      diet supplemented with a natural antioxidant, ubiquinone Q-9. The inhibiting
      effect of chronic irradiation was more pronounced in B lymphocytes because of
      their higher radiosensitivity.

PMID- 7738412
TI  - Photodynamic action increases leakage of the mitochondrial electron transport
      chain.
AB  - Rat liver submitochondrial particles were treated with rose bengal or flavin
      mononucleotide and irradiated with visible or near UV light. In both cases,
      oxygen consumption is impaired after irradiation while O2-. production increases
      significantly. This suggests that exogenous or endogenous photosensitizers can
      induce more electron leakage in the mitochondrial respiratory chain.
      Photobiological implications in dermatology are discussed.

PMID- 7738413
TI  - Suppression of tritium gas oxidation in rat by norfloxacin and clindamycin.
AB  - To determine whether intestinal anaerobes are the principal agents responsible
      for oxidation of tritium gas (HT) in the intestine, the suppressive effects of an
      antibacterial drug, norfloxacin, and an antibiotic, clindamycin, on tritium
      uptake in rat exposed to HT were investigated. The administration of norfloxacin
      or clindamycin to rat was started 1, 2, 3 or 4 days prior to exposure and
      continued until just before exposure to HT. Following exposure to HT for 2 h, the
      tritium concentration of tissues and blood was determined. Tritium concentration
      in blood decreased in proportion to the period of drug administration. In the
      case of clindamycin, the tritium concentration in the body of the rat decreased
      to 12% that in control rat. Norfloxacin was less effective than clindamycin. When
      the administration of clindamycin was begun on the day of exposure and continued
      for 4 days, the biological half life of urinary tritium in the treated rat was
      shortened to 53% that in the control rat.

PMID- 7738414
TI  - The practical management of artifact in computerised physiological data.
AB  - Computerised physiological data contains artifact that needs to be identified and
      possibly removed. Whilst computers may eventually satisfactorily perform this
      function, at present only manual removal is possible for the majority of
      intensive care computer groups. We assessed the effects of artifact and its
      removal on the physiological data of 3 patients. Artifact was manually removed
      from 7 days of data in 4 parameters (heart rate, respiratory rate, systolic blood
      pressure [sbp] and transcutaneous oxygen [tcpO2]) by 3 independent observers. Six
      hour time periods were analysed. Median and mean values before and after the
      manual removal of artifact were compared. Overall 6.5% of data was removed as
      artifact. This was greatest for tcpO2 (9.9%) and sbp (10.6%), with smaller
      amounts for respiratory rate (2.8%) and heart rate (2.4%). Sbp showed a marked
      difference in the amount of data removed between patients, whereas tcpO2 data
      contained quite large volumes of artifact, but this was fairly consistent between
      patients. Removal of artifact affected mean values more than median values. One
      observer considered that both physiological and non-physiological artifact should
      be removed, whereas the other two observers removed only non-physiological
      artifact. Agreement in results between the latter was good. Our results suggest
      that inter-observer variability should have a minimal effect on values, once
      rules identifying the type of artifact to be removed are agreed. Removal of
      artifact did not have a clinically significant effect on results, but may be an
      important consideration in the statistical analysis of computerised physiological
      data.

PMID- 7738415
TI  - The effect of a heat and moisture exchange filter on sidestream spirometry in
      critically ill patients.
AB  - Sidestream spirometry has enabled continuous on-line monitoring of the pulmonary
      mechanics in intubated patients. We studied the effect of the heat and moisture
      exchange filter (HMEF) on the displayed spirometry values of a commercial
      multiparameter pulmonary monitor in 35 stable ICU patients needing mechanical
      ventilatory support. There were statistically significant differences in tidal
      volumes, airway pressures, compliances and end-tidal CO2-values between the two
      sites of measurements on both sides on the HMEF. The effect of the HMEF was
      linear in almost every patient. However, the change of the displayed values was
      clinically of minor importance. In conclusion, we suggest that the HMEF can be
      safely used between the patient and the monitoring site in routine ventilatory
      monitoring of ICU patients.

PMID- 7738416
TI  - Computer supported multimodal bed-side monitoring for neuro intensive care.
AB  - Multimodal monitoring in neuro-intensive care requires computer supported data
      analysis and archiving. This paper describes a computer system that is able to
      integrate the results of analysis of intracranial pressure, cerebral perfusion
      pressure, transcranial Doppler blood flow velocity, jugular bulb oxygen
      saturation, laser Doppler blood flow, near infrared spectroscopy. A research
      oriented software installed in a standard IBM PC equipped with a low-cost analog
      to-digital converter allows a broad spectrum of waveform analyses, from
      calculation of simple mean values to a selective waveform detection and cross
      correlation analysis. The architecture for the signal processing algorithm, the
      principles of system interfacing and data presentation are discussed briefly.
      Results from two years of multimodal monitoring in neuro-intensive care show
      that, apart from simple recording of time trends of monitored variables, certain
      calculated parameters are particularly useful in the continuous assessment of
      cerebral haemodynamic and compensatory reserves. Such parameters include:
      transcranial Doppler pulsatility indices, the dependence between blood flow
      velocity or laser Doppler flux and cerebral perfusion pressure and the
      correlation coefficient between pulse amplitude and mean intracranial pressure.

PMID- 7738417
TI  - Data quality in computerized patient records. Analysis of a haematology biopsy
      report database.
AB  - This paper addresses the problem of data quality in electronic patient records
      using a computerized haematology biopsy report system as an example. Physicians
      extracted five parameters from a traditional free text cytology report and
      encoded these parameters thus producing a computer processable report. The
      parameters were 1) the organ biopsied, 2) quality of specimen, 3) cytological
      diagnosis including 4) a modifier code for the main diagnosis code (i.e. status
      post chemotherapy, Y-code) and 5) an additional key describing the degree of
      remission obtained after chemotherapy of acute leukemias. From the various steps
      involved in generating the electronic record we selected two critical ones:
      encoding of free text terms by physician staff; entering of the coded terms into
      a computer by lab staff. We analyzed the rates of correct, incorrect and missing
      codes for each of the five parameters. Our findings indicate that in this model
      of an electronic patient record: 1) there is significant inaccuracy of physicians
      during the process of encoding the free text report with error rates between 3.2
      and 28% and omission rates up to 64%. 2) lab staff entering these coded data into
      the computer introduce additional errors (0-7.8%) but rarely miss correctly
      encoded data (0-0.9%). 3) introducing a revised coding system data quality
      improved significantly (p < or = 0.001) with a fivefold increase of correct and a
      75% reduction of missing codes. 4) the clinical relevance of the diagnoses
      encoded as perceived by clinicians is a significant factor affecting error and
      omission rates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738418
TI  - Intelligent systems in patient monitoring and therapy management. A survey of
      research projects.
AB  - Although today's advanced biomedical technology provides unsurpassed power in
      diagnosis, monitoring, and treatment, interpretation of vast streams of
      information generated by this technology often poses excessive demands on the
      cognitive skills of health-care personnel. In addition, storage, reduction,
      retrieval, processing, and presentation of information are significant
      challenges. These problems are most severe in critical care environments such as
      intensive care units (ICUs) and operating room (ORs) where many events are life
      threatening and thus require immediate attention and the execution of definitive
      corrective actions. This article focuses on intelligent monitoring and control
      (IMC), or the use of artificial intelligence (AI) techniques to alleviate some of
      the common information management problems encountered in health-care
      environments. This article presents the findings of a survey of over 30 IMC
      projects. A major finding of the survey is that although significant advances
      have been made in introducing AI technology in critical care, successful examples
      of fielded systems are still few and far between. Widespread acceptance of these
      systems in critical care environments depends on a number of factors, including
      fruitful collaborations between clinicians and computer scientists, emphasis on
      evaluation studies, and easy access to clinical information.

PMID- 7738419
TI  - Calcium channel blockers and renal protection: is there an optimal dose?

PMID- 7738420
TI  - Agonist: the case for insulin resistance as a necessary and sufficient cause of
      type II diabetes mellitus.
AB  - The results of many cross-sectional studies have indicated that insulin
      resistance is a consistent, abnormal metabolic characteristic of people with
      NIDDM. Recently many investigators studying different populations have reported
      that insulin resistance is a prediabetic abnormality and is a major risk factor
      for the disease. Although deficient insulin secretion is also characteristic of
      people with NIDDM, there are no data to indicate that it precedes the onset of
      the disease, except in rare instances of families with glucokinase mutations.
      Therefore, in most cases, it appears that deficient insulin secretion occurs
      secondarily to insulin resistance, and there is experimental evidence indicating
      the mechanism of this effect. The clearest examples of this pathophysiologic
      mechanism are persons with insulin receptor mutations and severe insulin
      resistance in whom NIDDM develops despite normal insulin secretion. In addition,
      prospective studies have indicated that NIDDM rarely develops in the most insulin
      sensitive subjects, and the relatively lower insulin concentrations in patients
      with a known beta-cell defect--that is a glucokinase mutation--are compatible
      with normal glucose tolerance if ideal whole body insulin sensitivity is
      maintained. These data indicate beyond a reasonable doubt that insulin resistance
      is a sufficient cause of NIDDM and in most instances is necessary for its
      development.

PMID- 7738421
TI  - Antagonist: diabetes and insulin resistance--philosophy, science, and the
      multiplier hypothesis.

PMID- 7738422
TI  - Molecular genetics of thrombophilia: factor V gene mutation causing resistance to
      activated protein C as a basis of the hypercoagulable state.

PMID- 7738423
TI  - Effects of a calcium antagonist, manidipine, on progressive renal injury
      associated with mild hypertension in remnant kidneys.
AB  - The present study was conducted to determine the effects of a calcium antagonist,
      manidipine, on the outcome of a remnant kidney model of chronic renal failure in
      Fisher 344 rats. After sham operation or five-sixths nephrectomy (Nx), the rats
      were assigned to one of the following groups according to the administered amount
      of drug and were provided a specified diet for 12 weeks: group 1 (sham), diet
      without manidipine; group 2 (Nx), diet without manidipine; group 3 (Nx), diet
      with 0.0004% manidipine; group 4 (Nx), diet with 0.002% manidipine; group 5 (Nx),
      diet with 0.01% manidipine; group 6 (Nx), diet with 0.05% manidipine. All diet
      contained the same amount of calories (3.44 kcal/gm) and protein (25% casein).
      Systolic blood pressure and urinary protein excretion in group 2 began to
      increase at 8 and 4 weeks after ablation, respectively. Manidipine attenuated the
      increase in blood pressure in groups 4 through 6 but not in group 3. Manidipine
      treated groups 3 to 5 had significantly less proteinuria than group 2. Group 6
      had significantly more proteinuria than group 2. At 12 weeks after ablation, the
      kidneys from group 2 showed severe parenchymal damage, which is characteristic of
      end-stage renal pathology. These changes were ameliorated in groups 3 through 5,
      while group 6 had significantly more injured renal pathology than group
      2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738424
TI  - Characterization of mycobacterial antigens and antibodies in circulating immune
      complexes from pulmonary tuberculosis.
AB  - Circulating immune complexes (CICs) in serum samples from patients with pulmonary
      tuberculosis (bacteriologically positive [S+C+] and bacteriologically negative [S
      C-]) and controls (NHC) have been measured by using C1q binding assay (C1qBA) and
      3.5% polyethylene glycol precipitation and measurement of absorbance at 280 nm
      (PEG-OD 280). Although C1qBA did not show any difference between tuberculous and
      normal serum samples, PEG-OD 280 was significantly elevated in tuberculous
      samples. The effect of chemotherapy on CIC levels was studied. During the
      treatment, initially (for up to 2 months) there was a rise in CIC levels and
      later a fall, coinciding with bacterial clearance. Anti-purified protein
      derivative antibodies of class immunoglobulin G (IgG) and immunoglobulin M were
      measured in the serum samples and PEG precipitates. Anti-mycobacterial antibody
      measurement in CICs was more discriminatory between the groups than serum
      antibody. For characterization of the complexed antibody, the PEG precipitates
      were used in the Western blot and the patterns were compared. S+C+ CICs contained
      antibodies for a wide range of antigens ranging from 100 Kd to 10 Kd. However,
      none of the NHC-CICs contained antibodies for antigens < 70 Kd. Thus, when using
      the criterion of positivity for antibodies to antigens < 70 Kd as a marker for
      pulmonary tuberculosis, 24 of 24 (100%) of the S+C+ CICs were positive.
      Similarly, 11 of 16 (70%) of the S-C- CICs contained antibodies for antigens < 70
      Kd.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738425
TI  - Alpha 2b-interferon inhibits rat liver regeneration after partial hepatectomy
      without affecting thymidine kinase activity.
AB  - The effect of alpha 2b-interferon administration on liver regeneration after
      partial hepatectomy in male Wistar rats was examined 24 hours after the
      operation. Tritium thymidine incorporation into liver DNA, liver mass
      restitution, mitotic index, and nuclear expression of proliferating cell nuclear
      antigen were determined as indexes of hepatic proliferation. Both early and late
      alpha 2b-interferon administration, 2 and 12 hours, respectively, after partial
      hepatectomy, at a dose of 3.3 x 10(4) IU per kg body weight, suppressed tritium
      thymidine incorporation and liver mass restitution (p < 0.001) when compared with
      that in untreated partially hepatectomized rats. The enzyme thymidine kinase (EC
      2.7.1.21), a rate-determining enzyme of DNA biosynthesis, has been implicated in
      the suppression of proliferation in interferon-treated cell cultures. However, in
      the above-mentioned in vivo model of controlled cellular proliferation, thymidine
      kinase activity was not affected by alpha 2b-interferon administration, whereas
      DNA biosynthesis was inhibited. These findings, in contrast to previous
      observations in in vitro models, show that the inhibition of the in vivo liver
      regeneration by alpha 2b-interferon is not due to the inhibition of thymidine
      kinase activity. The expression of the cell cycle-related genes' products c-myc,
      p53, and c-erbB-2 proteins--which increase during the prereplicative phase that
      precedes DNA synthesis--was affected by interferon administration, being in
      accordance with liver proliferative status.

PMID- 7738426
TI  - Synergism of intratracheally administered tumor necrosis factor with interleukin
      1 in the induction of lung edema in rats.
AB  - Intratracheal (IT) instillation of human recombinant interleukin 1 (IL-1) in rats
      induces an influx of neutrophils into alveolar structures and a dose-dependent
      increase in lung vascular permeability. We sought to determine whether increased
      alveolar concentrations of tumor necrosis factor (TNF) enhanced lung injury
      induced by intrapulmonary administration of low-dose IL-1. Rats were divided into
      five groups and treated with IT instillation of saline (0.1 ml) containing (1) no
      additional compound (controls), (2) human recombinant IL-1 (10 ng), (3) human
      recombinant TNF (2 micrograms), (4) IL-1 + TNF (10 ng + 2 micrograms), or (5)
      lipopolysaccharide (LPS, 10 micrograms). At 3, 6, 24, and 48 hours after
      treatment, we counted neutrophils recovered by bronchoalveolar lavage (BAL),
      assessed TNF activity in BAL fluid, and measured lung wet:dry weight ratio. At 3
      and 6 hours after treatment, we measured levels of the lipid peroxide derivative
      malondialdehyde (MDA) in lung homogenates. IT instillation of LPS, IL-1, or IL-1
      + TNF rapidly increased BAL neutrophil recovery, whereas recovery was not
      increased by TNF alone. TNF activity in BAL fluid was markedly increased by LPS,
      TNF, and IL-1 + TNF, with a smaller increase induced by IL-1. Instillation of TNF
      or IL-1 alone at these doses did not increase the lung wet:dry ratio. IT
      administration of LPS increased the wet:dry ratio at 6 hours only (p < 0.05),
      whereas IL-1 + TNF increased this ratio beginning 3 hours (p < 0.01) after
      treatment with persistent increases through 48 hours (p < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7738427
TI  - Ethanol-induced alterations in messenger RNA levels correlate with glandular
      content of pancreatic enzymes.
AB  - Ethanol abuse is a well-known association of pancreatitis. The effects of chronic
      ethanol consumption on pancreatic digestive and lysosomal enzymes may be relevant
      to the pathogenesis of alcoholic pancreatitis, because pancreatic enzymes play an
      important role in the development of pancreatic injury. The aims of this study
      were to determine the effects of ethanol on gene expression and glandular content
      of pancreatic digestive enzymes and on gene expression of the lysosomal enzyme
      cathepsin B (known to be capable of activating trypsinogen). Pancreatic content
      and mRNA levels for lipase, trypsinogen, and chymotrypsinogen were determined in
      rats that were pair-fed a nutritionally adequate liquid diet with or without
      ethanol for 4 weeks. mRNA levels for the lysosomal enzyme cathepsin B were also
      assessed in this model. Ethanol significantly increased the content of lipase in
      the pancreas. There was a trend toward an increase in trypsinogen and
      chymotrypsinogen levels; however, these differences were not statistically
      significant. mRNA levels for lipase, trypsinogen, and chymotrypsinogen were
      raised in ethanol-fed rats. Ethanol feeding also increased mRNA levels for the
      lysosomal enzyme cathepsin B. Furthermore, there was a close, statistically
      significant correlation between changes in mRNA levels and tissue activities of
      pancreatic digestive and lysosomal enzymes after ethanol consumption. These
      results suggest that ethanol increases the capacity of the pancreatic acinar cell
      to synthesize digestive and lysosomal enzymes, thereby increasing the
      susceptibility of the gland to enzyme-related injury.

PMID- 7738428
TI  - Separation of VLDL subfractions by density gradient ultracentrifugation.
AB  - To assess the presence and composition of very-low-density lipoprotein (VLDL) in
      various types of hyperlipoproteinemia, a method of density gradient
      ultracentrifugation has been developed. After 2 hours of density gradient
      ultracentrifugation, human serum VLDL is separated into two distinct VLDL
      cholesterol peaks (VLDL1 and VLDL2). The two VLDL subfractions were detected in
      the serum samples from all subjects in the study, including subjects with
      normolipidemia (n = 10), familial dysbetalipoproteinemia (n = 12), and type IIa
      (n = 8), type IIb (n = 12), and type IV/V (n = 10) hyperlipoproteinemia. The
      cholesterol profiles obtained by the density gradient ultracentrifugation
      technique resembled the band patterns after electrophoresis of identical serum
      samples on 2% to 16% nondenaturing polyacrylamide gradient gel: VLDL1 represents
      relatively large VLDL particles (diameter of about 67 nm) and VLDL2 represents
      relatively small VLDL particles (diameter of about 38 nm). Recentrifugation of
      isolated VLDL1 and isolated VLDL2 did not result in any change in their density
      distribution. In all groups studied, the fluidity of VLDL1 was significantly
      higher than that of VLDL2, in accordance with the finding that VLDL1 particles
      were relatively rich in triglycerides and VLDL2 particles were relatively rich in
      cholesteryl esters. These results indicate that the two VLDL subfractions
      isolated represent distinct VLDL subclasses. The density gradient
      ultracentrifugation technique presented in this study allows the rapid isolation
      and characterization of VLDL subfractions from the serum samples of
      normolipidemic individuals and patients with hyperlipoproteinemia.

PMID- 7738429
TI  - Value of antibody level in diagnosing anhydride-induced immunologic respiratory
      disease.
AB  - The objective of this study was to determine whether immunologic anhydride
      induced respiratory disease could be predicted on the basis of the level of
      specific immunoglobulin E (IgE) or immunoglobulin G (IgG) antibody. Eight-one
      anhydride-exposed employees in one plant were studied. Fourteen had disease and
      67 did not. Immunologic studies were performed by enzyme-linked immunosorbent
      assay and expressed as titers. When optimal discriminant analysis was used, IgE <
      1:5 and IgG < or = 1:10 were found to be the optimal titers for separating
      employees with and without immunologic respiratory disease caused by anhydrides.
      When IgG < or = 1:10 was used, 62 of 81 workers were correctly classified; the
      sensitivity was 100%, the positive predictive value was 45%, the specificity was
      75%, and the negative predictive value was 100%. When IgE < 1:5 was used, 73 of
      81 workers were correctly classified; the sensitivity was 86%, the positive
      predictive value was 67%, the specificity was 91%, and the negative predictive
      value was 97%. In conclusion, anhydride disease status can be predicted on the
      basis of specific IgG or IgE antibody level.

PMID- 7738430
TI  - Sensitivity of HPLC and conventional bilirubin measurements in the detection of
      early cholestasis.
AB  - Recent studies using very sensitive high-performance liquid chromatography (HPLC)
      techniques have shown that conjugated bilirubin concentrations in normal human
      serum are about 0.006 mg/dl, much lower than the direct-reacting bilirubin
      concentrations reported by typical clinical laboratory techniques (up to 0.3
      mg/dl). In animal models of cholestasis, we tested the concept that HPLC
      measurements of true serum conjugated bilirubin would provide a more sensitive
      indicator of cholestasis than does the conventional measurement. Serum conjugated
      bilirubin was not detectable (< 0.006 mg/dl) in untreated rats and guinea pigs.
      After bile duct ligation, the true serum conjugated bilirubin concentration in
      rats was significantly elevated by 10 minutes, whereas the conventional bilirubin
      measurement did not become significantly elevated until 120 minutes; comparable
      values for the guinea pig were 30 and 240 minutes, respectively. Studies of two
      rat models of drug-induced cholestasis, cyclosporine A and 17 alpha
      ethynylestradiol, showed that measurable levels of true conjugated bilirubin
      appeared in the serum of cyclosporine A-treated rats but not in the estrogen
      treated animals. We conclude that true serum conjugated bilirubin concentrations
      measured by HPLC provide an extremely sensitive means of detecting cholestasis
      and that such measurements could have clinical utility in detecting very early or
      minimal liver dysfunction.

PMID- 7738431
TI  - Creating opportunities, or what is it like to be a WHALE?

PMID- 7738432
TI  - Learning disabilities, employment discrimination, and the ADA.
AB  - The Americans with Disabilities Act (ADA) of 1990 was intended to prohibit
      discrimination against individuals with disabilities. Although the scope of this
      legislation is broad, there are aspects of Title I and Title II of the ADA that
      may be of particular interest to persons with learning disabilities who are
      preparing for employment. This article discusses those aspects and presents case
      studies to demonstrate how the ADA could potentially be applied to typical
      situations. Suggestions are given for individuals with learning disabilities,
      their parents, and teachers with regard to employment preparation in secondary
      and postsecondary settings.

PMID- 7738433
TI  - Parent, teacher, peer, and self-reports of the social competence of students with
      learning disabilities.
AB  - The social competence of students with learning disabilities (LD), low
      achievement (LA), and average to high achievement (AHA) was examined from the
      perspectives of parents, teachers, peers, and self, guided by a theoretical model
      of social competence (Vaughn & Hogan, 1990) that includes social skills, behavior
      problems, peer relations, and self-perceptions. Parent ratings of social skills
      did not differ significantly among achievement groups; however, for two factors
      of behavior problems (internalizing and hyperactivity), students with LD and LA
      were rated as having more problems than AHA students. Teachers perceived students
      with LD and LA as demonstrating poorer social skills and more behavior problems
      than AHA students. Peer ratings indicated that students with LD and LA were less
      likely by peers than were AHA students, yet only LA students received
      significantly higher peer rejection. Self-reports differentiated the groups on
      one factor: cooperation. Discussion focuses on the complexity of social
      competence as a construct, and explanations of the results are offered.

PMID- 7738434
TI  - Information-processing patterns in specific reading disability.
AB  - This research investigated specific processing strengths and weaknesses among
      three groups of readers who ranged in age from 6 through 10 years. The first
      grade unsuccessful and the older unsuccessful readers had similar information
      processing patterns, whereas collectively they differed significantly from the
      first-grade successful readers on short-term auditory/working memory and
      decoding/encoding. When separately compared to the controls, the age-matched high
      risk group showed additional weakness in rapid automatized naming, and the
      reading-level-matched older disabled group showed additional weakness in
      phonological coding as well as visual sequential memory. Examination of second
      level classifications using cluster analysis suggested the presence of three
      potential subtypes among the 50 poor readers. All were characterized by
      difficulty in what was interpreted as symbolic processing/memory (Subtype 1),
      which occurred in combination with visual processing deficiencies (Subtype 2) and
      with deficits in both visual processing and rapid automatized naming (Subtype 3).

PMID- 7738435
TI  - The persistence of rapid naming problems in children with reading disabilities: a
      nine-year follow-up.
AB  - In this study 9 children (6 boys, 3 girls) with reading disabilities and specific
      difficulties in rapid serial naming were followed from age 9 years to age 18
      years. This group was taken from an earlier study sample of 82 third-grade
      children with learning disabilities. Tests of rapid serial naming, reading and
      spelling, general intelligence, articulation speed, and word fluency were
      administered to the subjects and to a matched control group (n = 10) in the
      initial study (at age 9) and in the present follow-up study (at age 18). The
      results showed that difficulties in both rapid naming and reading and spelling
      persisted into early adulthood in this subgroup. The development of naming speed
      is discussed in terms of a deficit model versus a developmental lag model of
      learning disability.

PMID- 7738436
TI  - Contrast sensitivity differences between proficient and disabled readers using
      colored lenses.
AB  - Colored overlays or lenses (e.g., Irlen lenses) have been used in attempts to
      remediate reading difficulties. The present study included four middle
      socioeconomic status (SES) adults and four middle-SES children with reading
      disabilities as well as an equal number of nondisabled readers of the same age
      groups and SES. Examined were (a) the relationship of wavelength (lens color) to
      visual grating performance, (b) the effect of reading disability on performance
      with each lens-color/luminosity-grating combination, (c) group performances on a
      visual detection task with the clear and chromatic lenses, and (d) peripheral
      retinal brightness thresholds. The spatial frequency of the gratings (and not the
      lens color) permitted subjects with reading disabilities to be differentiated
      from the proficient readers. Subjects with reading disabilities displayed
      significantly lower contrast sensitivity when tested with sine-wave gratings, as
      well as displaying higher brightness thresholds in the peripheral retina.

PMID- 7738437
TI  - A comparison between WISC-III and WISC-R scores for learning disabilities
      reevaluations.
AB  - This study examined differences between Wechsler Intelligence Scale for Children
      Third Edition (WISC-III) and Wechsler Intelligence Scale for Children-Revised
      (WISC-R) scores for 40 students with learning disabilities (LD) at the time of
      their triennial reevaluations. WISC-III Full Scale, Verbal, and Performance IQs
      were significantly lower than comparable WISC-R IQs by approximately one-third to
      one-half of a standard deviation. Correlations among the IQ scores were moderate
      to moderately strong. Implications of these findings for LD reevaluations are
      discussed.

PMID- 7738438
TI  - Family caregiving for older persons in the home. Medical-legal implications.

PMID- 7738439
TI  - Attacking defensive medicine through the utilization of practice parameters.
      Panacea or placebo for the health care reform movement?

PMID- 7738440
TI  - State consumer fraud legislation applied to the health care industry. Are health
      care professionals being "consumed"?

PMID- 7738441
TI  - HIV-related information and the tension between confidentiality and liberal
      discovery. The need for a uniform approach.

PMID- 7738442
TI  - On managed care and cutting edge technology.

PMID- 7738443
TI  - The world of Cybermedix.

PMID- 7738444
TI  - The information age: what's it all about?

PMID- 7738445
TI  - Single payer's last gasp?

PMID- 7738446
TI  - The use of positron emission tomography in clinical medicine.

PMID- 7738447
TI  - Price controls for drugs.

PMID- 7738448
TI  - Practice parameters gone sour: a case study.

PMID- 7738449
TI  - The moral significance of AIDS.

PMID- 7738450
TI  - Informed consent and anonymous tissue samples: the case of HIV seroprevalence
      studies.
AB  - Human Immunodeficiency Virus (HIV) seroprevalence studies use anonymous tissue
      samples obtained in hospitals and clinics without donor consent. This can be
      justified as a response to a public health emergency, but should not be seen as
      setting a precedent for waiving consent whenever samples are anonymous. The
      following recommendations grow out of this discussion: (1) Studies using
      anonymous tissue samples should not be automatically exempt from consent
      requirements, and consent should not be waived simply to avoid anticipated
      refusals, low participation rates or self selection bias. (2) The consensus on
      informed consent favors fulfilling as many of the elements of informed consent as
      reasonably possible, so studies should be assessed individually to determine if
      any or all elements of informed consent should be modified or omitted. (3) There
      is a need for greater regulation of the research use of tissue samples. (4)
      Investigators seeking approval to waive consent or modify elements of informed
      consent should document the sort of new findings that they believe would effect
      their calculations about the benefits and burdens to subjects who are enrolled in
      the study, and institutional review boards should indicate whether they agree
      with the investigators' analysis.

PMID- 7738451
TI  - Health care workers with HIV and a patient's right to know.
AB  - Accidental human immunodeficiency virus (HIV) infection of patients in health
      care settings raises the question about whether patients have a right to expect
      disclosure of HIV/AIDS diagnoses by their health workers. Although such a right
      and the correlative duty to disclose-might appear justified by reason of
      standards of informed consent, I argue that such standards should only apply to
      questions of risks of and barriers to HIV infection involved in a particular
      medical treatment, not to disclosure of personal diagnoses. Because the degree of
      risk of HIV infection is low and disclosure would also have damaging consequences
      for health workers, and because patient protection is available in other ways, it
      is argued that no such generalized right should be recognized.

PMID- 7738452
TI  - Going early, going late: the rationality of decisions about suicide in AIDS.
AB  - Where assistance in suicide is readily available to those dying of AIDS, as in
      the west coast gay communities of the United States and in the Netherlands, we
      must examine the different roles of physicians and friends (including lovers,
      spouses, family members, religious advisors, members of support groups, and
      intimate others) in helping a person with AIDS decide about and carry out
      suicide. This paper makes a central assumption: that where assistance in suicide
      is available, it is the moral obligation of others to protect and enhance as much
      as possible the rationality of that choice. Four components are identified in a
      rational choice about suicide in AIDS-whether it is a choice for or against
      suicide. Phrased as questions a person with AIDS might ask him- or herself, they
      are: (1) "Is suicide an option I want to consider?" (2) "Shall I hold out for the
      chance of a cure?" (3) "How shall I time my suicide?" (4) "What weight shall I
      give to the welfare and interests of others?" Although physicians often make
      assertions relevant to (1), they are appropriately involved only in (3); and
      although friends or intimate partners often provide the patient with anecdotal
      information relevant to (3), they should be involved primarily in (1). In short,
      both physicians and friends often intervene in the wrong parts of choices made by
      a person with AIDS about suicide.

PMID- 7738453
TI  - HIV preventive vaccine research: selected ethical issues.
AB  - This paper explores three selected issues which present ethical challenges unique
      to the development and testing of preventive HIV vaccines. The issues are: when
      to move forward with large scale efficacy testing of vaccines, how to incorporate
      behavioral interventions into the study of vaccine efficacy, and how to plan for
      and mitigate social harms associated with participation in an HIV vaccine trial.
      Careful and ongoing consideration must be given to the ethical implications of
      these decisions. Proposed solutions include planning for a more complex
      prevention trial which would integrate the evaluation of behavioral interventions
      and vaccine efficacy; scrupulous attention to the process of individual informed
      consent and community participation; and serious and deliberate attempts to plan
      for, educate about, and minimize the social harms.

PMID- 7738454
TI  - Oppressive limits: Callahan's foundation myth.
AB  - Daniel Callahan has not simply proposed alterations of important features of the
      health economy. He has constructed a blue print for society drawing on concepts
      of what is natural and appropriate to human beings. He is, in effect,
      establishing a new social order. Like any social order, Callahan's system has its
      justificatory schemes or founding myths. This paper offers a feminist examination
      of the functions that these four myths-the concept of a whole of life; the stages
      of life; a tolerable death; and a reconstruction of the meaning of the aged in
      terms of sacrifice-fulfill in Callahan's new social order. Callahan's concept of
      a whole of life reflects the power he assigns to nature, and the futility and
      harm he associates with attempts to repudiate biological imperatives. It
      introduces the stages of human life, tolerable death, and aging. The paper
      critically examines these concepts.

PMID- 7738455
TI  - Preventive ethics, professional integrity, and boundary setting: the clinical
      management of moral uncertainty.

PMID- 7738456
TI  - Does physician assisted suicide violate the integrity of medicine?
AB  - This paper evaluates the arguments against physician assisted suicide which
      contend that it violates the integrity of medicine and the physician-patient
      relation; i.e. that it contradicts the goal of seeking health and healing,
      violates an absolute prohibition against killing, and undermines the patient's
      trust in the physician. These arguments against physician assisted suicide (1)
      misuse notions of teleology and teleological explanation; (2) rely on
      inappropriate notions of "ideal medicine", for which death is a defeat; (3) turn
      on a highly selective reading for the Hippocratic tradition; and (4) are
      unacceptably paternalistic.

PMID- 7738457
TI  - Rationality and allocating scarce medical resources.
AB  - In an article titled, "Who Shall Live When Not All Can?", James Childress
      proposes a system for allocating scarce lifesaving medical resources based on
      random selection procedures. Childress writes of random selection procedures,
      [They] "cannot be dismissed as a 'non-rational' and 'non-human' ...without an
      inquiry into the reasons, including human values which might justify it." My
      thesis is that once we concentrate on determining the rationality of random
      selection procedures, we will see that Childress's claim that we cannot dismiss
      such procedures as 'non-rational' is open to question. My claim will be that
      while both random selection and social worth procedures are rationally defensible
      systems, random selection procedures easily lead to specific choices that are
      objectively irrational, apart from the limited perspective of the random
      selection process itself.

PMID- 7738458
TI  - Individual autonomy and the double-blind controlled experiment: the case of
      desperate volunteers.
AB  - This essay explores some concerns about the quality of informed consent in
      patients whose autonomy is diminished by fatal illness. It argues that patients
      with diminished autonomy cannot give free and voluntary consent, and that
      recruitment of such patients as subjects in human experimentation exploits their
      vulnerability in a morally objectionable way. Two options are given to overcome
      this objection: (i) recruit only those patients who desire to contribute to
      medical knowledge, rather than gain access to experimental treatment, or (ii)
      provide prospective subjects the choice to participate in standard double-blind
      study or receive the experimental treatment. Either option would guarantee that
      patients in desperate conditions are given a more meaningful choice and a richer
      freedom, and thus a higher quality of informed consent, than under standard
      randomized trials.

PMID- 7738459
TI  - A desperate solution: individual autonomy and the double-blind controlled
      experiment.
AB  - The randomization ingredient in double-blind controlled experiments may be
      objectionable to patients who, in their desperation, come to such trials seeking
      a last chance of cure. Minogue et al., who view such a situation as inherently
      exploitive and undermining of patient autonomy, propose that such "desperate
      volunteers" instead be enrolled in the active arm, while other patients, less
      desperate and more committed to medical progress, continue to be randomized.
      Their view is critiqued as destructive of medical progress, inappropriate in its
      lack of clinical response to such patients, and fatally flawed by unrealistic
      notions of autonomy and voluntariness.

PMID- 7738460
TI  - Can human genetic enhancement be prohibited?
AB  - This article seeks to reframe the ethical discussion of genetic enhancement,
      which is the use of genetic engineering to supply a characteristic that a parent
      might want in a child that does not involve the treatment or prevention of
      disease. I consider whether it is likely that enhancement can be successfully
      prohibited. If genetic enhancement is feasible, it is likely that there will be
      demand for it because parents compete to produce able children and nations
      compete to accumulate human capital in skilled workers. If some parents or
      nations begin using genetic enhancement, this will change these competitions in
      ways that increase the incentives for others to use it. Therefore, a ban on
      genetic enhancement would be unstable, because once the ban was breached by
      defectors the motivation of others to uphold it would weaken, making the ban
      liable to collapse. The argument provides a new perspective on slippery slopes to
      dangerous technology.

PMID- 7738461
TI  - The principlism debate: a critical overview.
AB  - Clouser and Gert's 'A Critique of Principlism' (1990) has ignited debate over the
      adequacy of substituting principlism for moral theory as a means for dealing with
      biomedical dilemmas. Clouser and Gert argue that this sort of substitution is not
      adequate to the task. I examine their argument in light of recent defences of
      principlism on this score, those of B. Andrew Lustig (1992), David Degrazia
      (1992), and Beauchamp and Childress (1994). I argue that both sides in the debate
      have assumed differing conceptions of a moral theory that virtually guarantee
      their respective conclusions. These differing conceptions are motivated by
      antecedent epistemological commitments. The present debate over principlism is
      therefore inconclusive. Future discussion should focus on the underlying
      epistemological issues.

PMID- 7738462
TI  - Vasopressin and vascular regulation: is sex a factor?

PMID- 7738463
TI  - Extracellular domain of prolactin receptor from bovine mammary gland: expression
      in Escherichia coli, purification and characterization of its interaction with
      lactogenic hormones.
AB  - The cDNA of the extracellular domain of bovine prolactin receptor (bPRLR-ECD) was
      cloned and expressed at high yield as an insoluble protein in Escherichia coli.
      This protein was solubilized, refolded and purified to > 98% homogeneity yielding
      80 mg of monomeric fraction per 2 litres of induced culture. Its molecular mass
      was 25.7 kDa, as determined by SDS-PAGE in the absence of reducing agent and 24
      kDa by gel filtration on a Superdex column. Binding experiments revealed that
      bPRLR-ECD binds to human (h) GH (hGH) with high affinity, whereas its affinity
      for ovine (o) or bovine (b) prolactins (PRLs) was lower and for bovine placental
      lactogen (bPL) very low. The affinity of bPRLR-ECD for the latter three hormones
      was, however, much higher than that of membrane-embedded or solubilized bPRLR.
      The stoichiometries of interaction of bPRLR-ECD with hGH, oPRL, bPRL and bPL were
      determined by gel-filtration chromatography. Even at a 3:1 ECD excess, only 1:1
      complexes were detected at microM concentrations of ECD and ligand. At an up to
      32-fold dilution, the complexes with oPRL, bPRL, and particularly bPL, underwent
      progressive dissociation, whereas the complex with hGH remained stable. Although
      all four hormones exhibited nearly identical activity in the Nb2 lymphoma cell
      bioassay, the ability of bPRLR-ECD to inhibit hormonal mitogenic activities
      differed, generally reflecting its affinity for the respective hormones. In view
      of these and previous results, we suggest that, unlike in the GH:GHR-ECD
      interaction, neither the stoichiometry of interaction of bovine or other PRLR
      ECDs nor the affinity constants can predict the biological potency of the
      different lactogenic hormones.

PMID- 7738464
TI  - Hypothalamic processing of beta-endorphin in female C57BL/6J mice is altered at
      middle age.
AB  - beta-Endorphin (beta-endo) (1-31) is the active opioid peptide product of pro
      opiomelanocortin processing. Further post-translational modifications of beta
      endo(1-31) yield beta-endo(1-27), (1-26) and their acetylated forms which are
      considered to be opiate receptor antagonists. Mechanistically, alteration in
      opiatergic properties is likely to result in the loss of a number of
      physiological functions including reproductive capacity. The purpose of this
      study was to determine whether there are changes in the way beta-endo neurones
      process the peptide with age in female C57BL/6J mice. Pooled extracts of arcuate
      nucleus (ARC) and preoptic area (POA) of 3- to 4-month-old normally cycling (4-5
      days at dioestrus), 12- to 13-month-old irregularly cycling (5-7 days at
      dioestrus), 23- to 24-month-old acyclic (in persistent dioestrus) animals were
      subjected to reversed-phase HPLC (n = 4 experiments). Column fractions were
      assayed for beta-endo-like-immunoreactivity by sequence-specific RIAs. The opiate
      receptor active as well as opiate receptor antagonist forms of beta-endo were
      present in both ARC and POA at all three age groups although their ratios varied.
      beta-Endo(1-31), the active opiate, was the predominant form in young animals. At
      middle age there was a threefold (P < 0.05, ANOVA) increase in the antagonist
      forms of beta-endo and this was associated with a significant (P < 0.05, ANOVA)
      increase in the ratio of antagonist to active forms. This was accompanied by a
      trend toward an increase in acetylated forms of beta-endo in middle-aged mice.
      HPLC profiles from hypothalami of old animals more closely resembled those of
      young females. The increase in the antagonist forms of beta-endo at middle age
      may contribute to a decline of opiatergic influences in the female C57BL/6J mouse
      and suggest a mechanism whereby alterations in opiate influence over
      gonadotrophin control may occur.

PMID- 7738465
TI  - Induction of immediate early gene mRNAs and proteins by hCG in interstitial cells
      of rat testis.
AB  - In the present study we have investigated the induction of immediate early gene
      (IEG) c-fos, c-jun, junB and junD mRNAs and proteins in interstitial cells of rat
      testis after hCG treatment in vivo using in situ hybridization and
      immunocytochemistry. The basal levels of all IEGs were barely detectable with our
      methods. A prominent induction of c-fos, c-jun and junB mRNAs and proteins in
      Leydig cells was seen after hCG treatment. The induction of these IEG mRNAs and
      proteins demonstrates that their expression is an early transcriptional response
      to the extracellular stimulus of hCG and that they are involved in
      transcriptional processes which may mediate the effects of LH on cellular
      adaptive responses or steroid biosynthesis.

PMID- 7738466
TI  - Effects of neuroleptic treatment on cortisol and 3-methoxy-4-hydroxyphenylethyl
      glycol levels in blood.
AB  - Plasma cortisol and serum 3-methoxy-4-hydroxyphenylethyl glycol (MHPG) were
      determined before and after 5-6 weeks of neuroleptic treatment in patients with
      schizophrenia. Following drug treatment both plasma cortisol and serum MHPG
      levels in patients decreased and plasma cortisol levels were also lower than in
      unmedicated healthy controls. Indications of a relationship between the reduction
      of cortisol and MHPG levels were found. The data show that neuroleptic drug
      treatment inhibits cortisol secretion. It is speculated that this inhibition
      could be related to reduced noradrenergic activity.

PMID- 7738467
TI  - Dietary omega 6 fatty acids and the effects of hyperthyroidism in mice.
AB  - The influence of the type of dietary fat on the effects of thyroid hormones was
      investigated in mice. Hyperthyroidism was achieved by providing thyroid hormones
      (T3 and T4) in the drinking water. Both hyperthyroid and euthyroid mice (Mus
      musculus) were fed isoenergetic diets containing 18% (w/w) total lipid but
      differing in fatty acid composition. Diets were either low in the polyunsaturated
      linoleic acid (18:2, omega 6) and high in saturated fatty acids (SFAs) or low in
      saturated fats and high in the polyunsaturated fatty acid (PUFA), linoleic acid.
      Treatments were maintained for 21-22 days. Plasma thyroid hormone levels,
      standard metabolic rate (SMR), changes in body mass, specific activities of malic
      enzyme (ME), Na-K-ATPase and glycerolphosphate dehydrogenase (GPDH) of the liver
      were measured. Fatty acid composition of the liver phospholipids was also
      determined. Levels of T3 (15-17 nM) and T4 (250-255 nM) were significantly higher
      in the respective hyperthyroid groups. There was no significant influence of the
      diet on hormone levels. Hyperthyroidism increased the SMR 37-44% above the
      euthyroid levels. A significant body weight loss of 14-18% was observed in
      hyperthyroid mice on the PUFA diet but not in those on the SFA diet. PUFA diet
      significantly reduced the activity of ME but had no effect on Na-K-ATPase or GPDH
      activity. Activities of Na-K-ATPase and GPDH were significantly elevated in all
      hyperthyroid groups. Mice on T4 and PUFA diet showed a highly significant 399%
      increase in GPDH activity above the euthyroid level.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7738468
TI  - Do vasopressin and oxytocin have synergistic renal effects in the conscious rat?
AB  - The renal effects of arginine vasopressin and oxytocin were studied in the
      conscious unrestrained rat infused with 0.077 M NaCl. Peptides were infused at
      rates of 24 and 160 pmol/min (vasopressin) or 30 and 200 pmol/min (oxytocin)
      either alone or as a combination of the two lower or two higher doses. The rates
      of infusion were selected to give ratios of oxytocin:vasopressin similar to those
      seen in the plasma of euhydrated and dehydrated rats. Vasopressin produced dose
      dependent antidiuretic and natriuretic responses, the natriuresis commencing
      after 15-30 min infusion. Oxytocin produced dose-dependent diuretic and
      natriuretic responses, the natriuresis commencing within the first 15 min of
      infusion. Combined infusion of vasopressin and oxytocin produced dose-dependent
      antidiuretic responses which were comparable to those seen with vasopressin
      alone. The natriuretic response from combined infusion at the higher rate
      appeared to have the greater magnitude for individual 15-min periods of the
      vasopressin response combined with the longer duration of the oxytocin response.
      Although the total natriuretic response was therefore greater, this difference
      failed to reach significance. Only the higher rates of infusion of vasopressin
      and oxytocin significantly increased the clearance of sodium, by 53 +/- 23 and 62
      +/- 18% and glomerular filtration rate (GFR) by 23 +/- 4 and 23 +/- 4%
      respectively. The clearance of sodium during the combined hormone infusion was
      significantly greater (109 +/- 21%), while the rise in GFR at 23 +/- 5% was
      comparable to that seen when each hormone was given separately.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7738469
TI  - Reduced liver insulin-like growth factor-I gene expression in young zinc-deprived
      rats is associated with a decrease in liver growth hormone (GH) receptors and
      serum GH-binding protein.
AB  - Zinc depletion attenuates growth and decreases circulating IGF-I. To investigate
      the mechanisms responsible for the IGF-I decline, we determined the effects of
      dietary zinc (Zn) deficiency on body and organ growth, serum IGF-I, serum GH
      binding protein (GHBP), liver GH receptors and liver expression of their
      corresponding gene. After 1 week of adaptation to a normal zinc diet, a zinc
      deficient diet (ZD; Zn, 0 p.p.m.) or a zinc-normal diet (CTR; Zn, 75 p.p.m.) was
      available ad libitum to 4-week-old Wistar rats for 4 weeks. Pair-fed animals (PF)
      received the zinc-normal diet in the same absolute amount as that consumed the
      day before by the ZD group. The food intake of ZD and PF rats was reduced by 32%
      (P < 0.001) compared with the CTR group. Zinc depletion specifically reduced body
      weight gain (-22%, P < 0.05), serum IGF-I concentrations (-52%, P < 0.001),
      hepatic GH receptors (-28%; P < 0.05) and serum GHBP levels (-51%; P < 0.05),
      compared with the PF group. GH concentrations were reduced in ZD animals compared
      with CTR rats (P < 0.01). The caloric restriction of PF animals also decreased
      body weight gain (-50%, P < 0.001), serum IGF-I concentrations (-21%, P < 0.05),
      liver GH receptors (-38%, P < 0.001) and serum GHBP levels (-38%, P < 0.01), when
      compared with the CTR group. Both ZD and PF groups had reduced liver IGF-I and GH
      receptor/GHBP mRNA levels in comparison with the CTR group (P < 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7738470
TI  - Differential effect of selective block of alpha 2-adrenoreceptors on plasma
      levels of tumour necrosis factor-alpha, interleukin-6 and corticosterone induced
      by bacterial lipopolysaccharide in mice.
AB  - The effect of selective block of alpha 2-adrenoreceptors on plasma levels of
      tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and corticosterone
      induced by bacterial lipopolysaccharide (LPS) was investigated in mice using
      ELISA and RIA. It was found that the LPS-induced TNF-alpha response was
      significantly blunted in mice pretreated with CH-38083, a novel and highly
      selective alpha 2-adrenoreceptor antagonist (the alpha 2/alpha 1 ratio is >
      2000). In contrast, LPS-induced increases in both corticosterone and IL-6 plasma
      levels were further increased by CH-38083. Since it has recently been shown that
      the selective block of alpha 2-adrenoreceptors located on noradrenergic axon
      terminals resulted in an increase in the release of noradrenaline (NA), both in
      the central and peripheral nervous systems, and, in our experiments, that
      propranolol prevented the effect of alpha 2-adrenoreceptor blockade on TNF-alpha
      plasma levels induced by LPS, it seems likely that the excessive stimulation by
      NA of beta-adrenoreceptors located on cytokine-secreting immune cells is
      responsible for this action. Since it is generally accepted that increased
      production of TNF-alpha is involved in the pathogenesis of inflammation and
      endotoxin shock on the one hand, and corticosterone and even IL-6 are known to
      possess anti-inflammatory properties on the other hand, it is suggested that the
      selective block of alpha 2-adrenoreceptors might be beneficial in the treatment
      of inflammation and/or endotoxin shock.

PMID- 7738471
TI  - Effects of hemitransection of the midbrain on milk-ejection burst of oxytocin
      neurones in lactating rat.
AB  - Unilateral knife cuts were performed in the midbrain of lactating rats and the
      activities of oxytocin neurones were recorded extracellularly from the supraoptic
      nuclei (SON) in order to investigate the location of the neural mechanism
      responsible for the synchronization of milk-ejection bursts of oxytocin neurones
      in different magnocellular nuclei of the hypothalamus. The lesions involved the
      mesencephalic lateral tegmentum, the intermedial tegmentum and the central grey.
      Ninety-six SON neurones were antidromically activated by neurohypophyseal
      stimulation and were also identified as oxytocin neurones, which included 17 pair
      recorded neurones. First, the response of oxytocin neurones recorded from the
      unilateral SON to bilateral or unilateral suckling was tested. During bilateral
      suckling, not only the oxytocin neurones recorded from the SON on the intact side
      (n = 34) but also those recorded from the SON on the lesioned side (n = 58)
      displayed milk-ejection bursts. When only the nipples ipsilateral to the lesion
      were suckled (ipsilateral suckling), bursts were induced in most of the oxytocin
      neurones on the intact (83.3%, n = 12) and lesioned side (88.9%, n = 27). In
      contrast, none of the oxytocin neurones (n = 37) produced bursts and none of the
      rats tested (n = 23) showed milk ejections during contralateral suckling.
      Secondly, some characteristics of the bursts of pair-recorded neurones during
      bilateral suckling and their response to different modes of suckling were
      investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738472
TI  - Seasonal and photoperiod-induced changes in the secretion of alpha-melanocyte
      stimulating hormone in Soay sheep: temporal relationships with changes in beta
      endorphin, prolactin, follicle-stimulating hormone, activity of the gonads and
      growth of wool and horns.
AB  - Blood plasma concentrations of alpha-melanocyte-stimulating hormone (alpha-MSH),
      beta-endorphin (beta-END), prolactin and follicle-stimulating hormone (FSH), and
      associated changes in the size of the testes, and growth of the horns and pelage
      were measured in male (n = 8), castrated male (n = 5) and female (n = 9) Soay
      sheep. The animals were born in April and kept outdoors near Edinburgh (56
      degrees N) during the first two years of life. In all groups there was a close
      association between the weekly changes in the plasma concentrations of alpha-MSH
      and beta-END; the molar ratio in mean concentrations was close to 1:1. The blood
      plasma concentrations of both hormones varied markedly with season with a 3- to
      10-fold increase in concentrations from the minimum in winter to the maximum in
      autumn. The seasonal peak occurred in September in the first year of life as
      juveniles, and between July (males) and September (females) in the second year
      when the animals were sexually mature. The plasma concentrations of ACTH did not
      vary in parallel with the seasonal changes in the concentrations of alpha-MSH
      (measured only in males); the molar ratio for the concentrations of alpha
      MSH:ACTH was 1:0.12. The seasonal increase in the concentrations of alpha-MSH
      occurred 1-3 months after the seasonal increase in the concentrations of
      prolactin and the associated growth in horns and pelage, and slightly before, or
      coincident with the seasonal increase in the concentrations of FSH and the growth
      in the testes. In a second experiment, the same parameters were measured in a
      group of adult male Soay sheep (n = 8) housed indoors under an artificial
      lighting regimen of alternating 16-week periods of long (16 h light: 8 h
      darkness) and short days (8 h light: 16 h darkness). In this situation, there was
      a clearly defined photoperiod-induced cycle in the plasma concentrations of alpha
      MSH with a 25-fold increase from a minimum under long days to a maximum under
      short days. The concentrations of beta-END varied in close parallel with the
      changes in alpha-MSH, and the temporal associations with the changes in the other
      pituitary hormones were similar to those observed in animals housed outdoors.
      Overall, the results support the view that alpha-MSH is co-secreted with beta-END
      from the melanotrophs in the pars intermedia of the pituitary gland, and that the
      secretory activity of the melanotrophs changes markedly with season, increasing
      in summer and autumn, and decreasing in winter and spring.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7738473
TI  - Changes in glucocorticoid receptor mRNA in the developing ovine pituitary and the
      effects of exogenous cortisol.
AB  - Developmental changes in pituitary glucocorticoid receptor (GR) mRNA were
      examined during gestation and early neonatal life using in situ hybridization.
      Pituitaries were harvested from sheep fetuses at days 60-80, 100-120, 130-135,
      140-142 and term, and from lambs of days 0-7 and 30-60, and adults. GR mRNA was
      present in the pars distalis by day 60, levels increased through gestation, and
      there was a redistribution of GR mRNA, resulting in a relatively greater
      abundance at the base of the pars distalis. At term, there was a significant (P <
      0.05 compared with the day 140-142 fetuses) elevation of GR mRNA, which was
      maintained in the newborn lamb, reaching highest levels at days 30-60 of neonatal
      life. GR mRNA was undetectable in the pars intermedia until day 120, but
      subsequently increased to high levels at term. Interestingly, the expression of
      GR mRNA in the pars intermedia dropped precipitously in the newborn (P < 0.05
      compared with term), though levels recovered in the older lambs and adults. The
      regional and cellular distribution of GR mRNA correlated closely with the
      presence of immunoreactive GR (irGR) in the pituitary; the majority of irGR was
      present in the nuclei. Intrafetal infusion of cortisol (12 h; 5 micrograms/min)
      in late gestation (day 135) had no effect on Gr mRNA expression in either the
      pars distalis or pars intermedia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738474
TI  - Action of opioid peptides on the rat adrenal cortex: stimulation of steroid
      secretion through a specific mu opioid receptor.
AB  - While there have been several studies on the actions of opioid peptides on
      adrenocortical steroidogenesis, the results of these studies have failed to
      resolve the question as to whether these peptides exert a direct action on the
      adrenal cortex. The present studies were designed to address this question
      directly, using collagenase-dispersed rat zona glomerulosa and zonae
      fasciculata/reticularis cells incubated in vitro. The results obtained clearly
      show that the opioid peptides tested (beta-endorphin, Leu-enkephalin, Met
      enkephalin, and its long-acting analogue, DALA) all exerted a significant
      stimulatory effect on aldosterone secretion by zona glomerulosa cells and all,
      except Leu-enkephalin, stimulated corticosterone secretion by inner zone cells.
      The response was shown to be inhibited by naloxone. There did not appear to be a
      significant interaction between the effects of ACTH and the opioid peptides on
      adrenocortical cells. Studies using specific agonists for opioid receptor
      subtypes (DAMGO, DPDPE and U-50488H, specific for mu, delta and kappa receptors
      respectively) showed that the effect of opioid peptides on the zona glomerulosa
      appeared to be mediated exclusively by mu receptors while the response of inner
      zone cells was mediated by both mu and, to a lesser extent, kappa receptors.
      Finally, studies on the second messenger systems activated by the opioid peptides
      and the receptor agonists showed that these peptides act to increase labelling of
      inositol trisphosphate, and strongly suggest that, in the rat adrenal cortex,
      both mu and kappa opioid receptors are linked to the activation of phospholipase
      C.

PMID- 7738475
TI  - Effects of catecholamine synthesis inhibitors and adrenergic receptor antagonists
      on restraint-induced LH release.
AB  - Acute stress is known to increase LH secretion and the release of central
      norepinephrine (NE) in intact rats. Studies were performed to analyse the ole of
      catecholamines in acute stress-induced LH release in male rats. Injection of
      alpha-methyl-p-tyrosine (alpha MPT) and diethyldithiocarbamate (DDC),
      catecholamine synthesis inhibitors, significantly decreased both hypothalamic
      concentration of NE and serum LH. Restraint for 30 min evoked an increase in
      serum LH in saline-treated rats, whereas alpha MPT and DDC administration blocked
      the stress-induced LH release. The effects of alpha 1-, alpha 2- and beta
      adrenoreceptor antagonists on the LH response to restraint stress were also
      studied. Propranolol treatment did not modify serum LH in either unstressed or
      stressed rats. The two alpha-adrenergic receptor antagonists prazosin and
      yohimbine prevented the restraint-induced LH release; however, prazosin but not
      yohimbine significantly decreased the serum concentration of LH in unstressed
      rats. These data suggest that the acute stress-induced increase in LH secretion
      is mediated through the activation of alpha 2-adrenergic receptors.

PMID- 7738476
TI  - In vitro 19-norandrogen synthesis by equine placenta requires the participation
      of aromatase.
AB  - Explants of equine full-term placenta have been shown to synthesize 19
      norandrogens from labelled androgens. Steroid metabolites were purified by silica
      gel column chromatography then analysed and quantified by c18-reverse-phase HPLC
      coupled to a radioactive flow detector. 19-Norandrostenedione was subsequently
      recrystallized to constant specific activity, providing unequivocal evidence of
      its synthesis by the equine placenta. 19-Norandrostenedione synthesis appeared to
      be localized in the microsomal fraction. Regardless of the substrate used,
      formation of 19-norandrogens was far weaker than that of oestrogens; moreover,
      the yield of 17-oxosteroids produced was much greater than that of 17 beta
      hydroxysteroids, suggesting the presence of a dehydrogenase with predominant
      oxidative activity. Sulphoconjugated steroids formed were less than 0.5% of total
      steroids. Although 19-nortestosterone could not be generated by equine purified
      aromatase incubated with labelled testosterone, the synthesis of 19-norandrogens
      and oestrogens by equine placental explants was blocked by two specific aromatase
      inhibitors, 4-hydroxyandrostenedione and fadrozole. Our results provide evidence
      for a placental origin of at least a part of the 19-norandrogens previously
      identified in the blood of the pregnant mare. Furthermore, it is suggested that
      19-norandrogen biosynthesis would involve the enzymatic metabolism of 19
      oxygenated androgens formed by equine aromatase.

PMID- 7738477
TI  - Inositol 1,4,5-trisphosphate 3-kinase activity in FRTL-5 cells: regulation of the
      enzyme activity by TSH.
AB  - Inositol 1,4,5-trisphosphate (InsP3) 3-kinase phosphorylates the Ca(2+)
      mobilizing second messenger InsP3 to inositol 1,3,4,5-tetrakisphosphate (InsP4).
      InsP3 5-phosphatase dephosphorylates InsP3 to inositol 1,4-bisphosphate (InsP2).
      We compared the effects of TSH added to a culture of FRTL-5 thyroid cells on the
      activity of InsP3 5-phosphatase and InsP3 3-kinase. InsP3 3-kinase activity was
      decreased at a physiological concentration of TSH. Inhibition of this activity
      started after 3 h of incubation with TSH and was maximal after 24 h. In contrast,
      InsP3 5-phosphatase activity was not affected by TSH under the same conditions.
      The inhibitory effect of TSH on InsP3 3-kinase was characterized as follows: a)
      inhibition of activity was mimicked by both dibutyryl cyclic AMP and forskolin;
      b) activity obtained by mixing lysates of TSH-stimulated and non-stimulated cells
      was the sum of each activity measured separately; c) inhibition persisted after a
      crude lysate of TSH-stimulated cells had been subjected to SDS/polyacrylamide gel
      electrophoresis and the extraction of InsP3 3-kinase activity. The data suggest
      that TSH reduced the activity of InsP3 3-kinase in FRTL-5 cells either by a
      phosphorylation/dephosphorylation mechanism, or by affecting expression of the
      enzyme.

PMID- 7738478
TI  - Effects of indigestible dextrin on glucose tolerance in rats.
AB  - A recently developed indigestible dextrin (IDex) was studied for its effects on
      glucose tolerance in male Sprague-Dawley rats. IDex is a low viscosity, water
      soluble dietary fibre obtained by heating and enzyme treatment of potato starch.
      It has an average molecular weight of 1600. An oral glucose tolerance test was
      conducted with 8-week-old rats to evaluate the effects of IDex on the increase in
      plasma glucose and insulin levels after a single administration of various sugars
      (1.5 g/kg body weight). The increase in both plasma glucose and insulin levels
      following sucrose, maltose and maltodextrin loading was significantly reduced by
      IDex (0.15 g/kg body weight). This effect was not noted following glucose, high
      fructose syrup and lactose loading. To evaluate the effects of continual IDex
      ingestion on glucose tolerance, 5-week-old rats were kept for 8 weeks on a stock
      diet, a high sucrose diet or an IDex-supplemented high sucrose diet. An oral
      glucose (1.5 g/kg body weight) tolerance test was conducted in week 8. Increases
      in both plasma glucose and insulin levels following glucose loading were higher
      in the rats given a high sucrose diet than in the rats fed a stock diet. However,
      when IDex was included in the high sucrose diet, the impairment of glucose
      tolerance was alleviated. Moreover, IDex feeding also significantly reduced
      accumulation of body fat, regardless of changes in body weight. These findings
      suggest that IDex not only improves glucose tolerance following sucrose, maltose
      and maltodextrin loading but also stops progressive decrease in glucose tolerance
      by preventing a high sucrose diet from causing obesity.

PMID- 7738479
TI  - Central effects of growth hormone-releasing hexapeptide (GHRP-6) on growth
      hormone release are inhibited by central somatostatin action.
AB  - Growth hormone (GH) release is stimulated by a variety of synthetic
      secretagogues, of which growth hormone-releasing hexapeptide (GHRP-6) has been
      most thoroughly studied; it is thought to have actions at both pituitary and
      hypothalamic sites. To evaluate the central actions of this peptide, we have
      studied GH release in response to direct i.c.v. injections in anaesthetized
      guinea pigs. GHRP-6 (0.04-1 microgram) stimulated GH release > 10-fold 30-40 min
      after i.c.v. injection. The same GH response required > 20-fold more GHRP-6 when
      given by i.v. injection. GH release could also be elicited by a non-peptide GHRP
      analogue (L-692,585, 1 microgram i.c.v.), whereas a growth hormone-releasing
      factor (GRF) analogue (human GRF27Nle(1-29)NH2, 2 micrograms, i.c.v.) was
      ineffective. A long acting somatostatin analogue (Sandostatin, SMS 201-995, 10
      micrograms i.c.v.) (SMS) given 20 min before 200 ng GHRP-6 blocked GH release.
      This was unlikely to be due to a direct effect of SMS leaking out to the
      pituitary, since central SMS injections did not affect basal GH release, nor did
      they block GH release in response to i.v. GRF injections. We conclude that the
      hypothalamus is a major target for GHRP-6 in vivo. Since the GH release induced
      by central GHRP-6 injections can be inhibited by a central action of
      somatostatin, and other data indicate that GHRP-6 activates GRF neurones, we
      suggest that somatostatin may block this activation via receptors known to be
      located on or near the GRF cells themselves. Somatostatin may therefore be a
      functional antagonist of GHRP-6 acting centrally, as well as at the pituitary
      gland.

PMID- 7738480
TI  - Serum thyrotropin (TSH) heterogeneity in euthyroid subjects and patients with
      subclinical hypothyroidism: the core fucose content of TSH-releasing hormone
      released TSH is altered, but not the net charge of TSH.
AB  - The aims of the present study were to determine the influence of brief
      subclinical hypothyroidism on the isoforms of serum thyrotropin (TSH) and to
      examine the net charge of TSH in different metabolic states. Sera were obtained
      from euthyroid subjects (n = 7) and from patients with subclinical hypothyroidism
      (n = 8) before and 30 min after the intravenous administration of 200 micrograms
      thyrotropin-releasing hormone (TRH). The TSH from human pituitary extracts (IRP
      68/38), basal and TRH-stimulated serum TSH was immunoconcentrated and further
      analysed by isoelectric focusing (IEF) and lentil lectin affinity chromatography.
      TSH immunoreactivity was determined in each specimen or fraction with an
      automated highly sensitive chemiluminometric TSH assay. We found that basal TSH
      in subclinical hypothyroidism, and TRH-released TSH in euthyroidism and in
      subclinical hypothyroidism is distributed in a similar neutral to acidic pattern,
      which significantly differs from the more alkaline to neutral isoform pattern of
      intrapituitary TSH (P < 0.05). IEF analysis of pituitary standard TSH revealed 3
      major peaks (pI values 7.5; 6.6; 5.8) whereas in most euthyroid or subclinically
      hypothyroid subjects 5 peaks were found. Lentil lectin affinity chromatography
      revealed that TRH-released TSH in euthyroid subjects has more core fucose
      residues than TSH from patients with subclinical hypothyroidism (64.6 +/- 6.7 vs
      12.5 +/- 2.7%, P < 0.0001). Thus pituitary standard TSH seems to be less mature
      material than circulating TSH. Perhaps no alteration in the IEF pattern of TSH
      was detected during early hypothyroidism because sialylation of TSH was
      increasing as sulfatation was decreasing. Nevertheless, a change in the core
      fucose content of TSH was detectable by lentil analysis.

PMID- 7738481
TI  - Increasing gestational age and cortisol alter the ratio of ACTH precursors:ACTH
      secreted from the anterior pituitary of the fetal sheep.
AB  - We have used a perifusion system and slices of the anterior pituitary of the
      fetal sheep combined with specific immunoradiometric assays to investigate the
      effect of increasing gestational age and cortisol infusion on the output of
      ACTH(1-39) and the ACTH precursors, pro-ACTH and pro-opiomelanocortin, from the
      fetal sheep pituitary. Two slices from each fetal anterior pituitary at 106-113
      days (n = 3), 120-136 days (n = 5) and 140-143 days (n = 5) of gestation were
      used. Slices from each anterior pituitary were perifused with the perifusion
      buffer for at least 120 min prior to the infusion of cortisol (100 nM) for 30 min
      or buffer alone (control). The anterior pituitary output (fmol/5 min per mg
      pituitary) of ACTH(1-39) and the ACTH precursors were measured using specific
      immunoradiometric assays. There was a significant increase in the anterior
      pituitary secretion rate of ACTH(1-39) between 120 and 136 days (1.04 +/- 0.23
      fmol/5 min per mg) and between 140 and 143 days of gestation (3.08 +/- 0.33
      fmol/5 min per mg). In contrast, there was no change in the secretory rate of the
      ACTH precursors between 105 and 143 days of gestation. The ratio of the anterior
      pituitary output of the ACTH precursors:ACTH(1-39) therefore decreased between
      120 and 143 of days gestation from 19.10 +/- 2.05 to 6.36 +/- 0.58. There was no
      effect of cortisol infusion on the anterior pituitary secretion of either ACTH(1
      39) or the ACTH precursors before 116 days of gestation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7738482
TI  - Smoking elicits the insulin resistance syndrome: new aspects of the harmful
      effect of smoking.

PMID- 7738483
TI  - Management of corticosteroid-induced osteoporosis. UK Consensus Group Meeting on
      Osteoporosis.
AB  - Corticosteroid therapy results in osteoporosis. There is a doubling in the risk
      of fracture in patients taking more than the equivalent of 7.5 mg day-1. The bone
      loss is most rapid from the axial skeleton, particularly during the 1st year of
      therapy. The most important mechanism for the bone loss is a decrease in
      osteoblastic activity. Preventative strategies should be targeted to patients
      with low bone-mineral density, especially if the dose of corticosteroids is
      likely to be high. Treatment strategies agreed on by the Consensus Panel included
      hormone replacement therapy and bisphosphonates, with monitoring of efficacy by
      bone densitometry.

PMID- 7738484
TI  - Lipid intolerance in smokers.
AB  - OBJECTIVES: Smokers have recently been shown to be insulin resistant and to
      exhibit several characteristics of the insulin resistance syndrome (IRS). In this
      study, we assessed fasting and postprandial lipid levels in healthy,
      normolipidaemic, chronic smokers and a matched group of non-smoking individuals.
      DESIGN: A standardized mixed meal (containing 3.78 MJ and 51 g of fat) was given
      in the morning after an overnight fast. The smokers were either abstinent from
      tobacco for 48 h or were allowed to smoke freely, including being allowed to
      smoke six cigarettes during the study. SUBJECTS: Twenty-two middle-aged, healthy
      male subjects, nine habitual smokers and 13 non-smoking control subjects, were
      recruited to the study. The smokers had all been smoking at least 10 cigarettes
      per day for at least 10 years. RESULTS: The smokers exhibited a lipid intolerance
      in that their postprandial increase in triglyceride levels was more than 50%
      higher than in the non-smokers' group. This lipid intolerance could not be
      discerned in the postabsorptive state because the fasting triglyceride levels
      were the same in both groups, while the smokers had significantly lower high
      density lipoprotein (HDL) cholesterol. The peak postprandial triglyceride level
      correlated closely and negatively with fasting HDL cholesterol, indicating an
      impaired lipolytic removal capacity in smokers. CONCLUSIONS: Healthy,
      normotriglyceridaemic smokers exhibit an abnormal postprandial lipid metabolism
      consistent with lipid intolerance. It is suggested that postprandial
      hyperlipidaemia is a characteristic trait of the insulin resistance syndrome and
      that the defect in lipid removal is related to the low HDL cholesterol in this
      syndrome. The insulin resistance syndrome is likely to be an important reason for
      the increased propensity for cardiovascular disease in smokers.

PMID- 7738485
TI  - Interrelation between risk factors for cardiovascular disease in men aged 33-42.
      A study from Habo in Skaraborg County, Sweden.
AB  - OBJECTIVES: The main purpose was to study associations between different risk
      factors for coronary heart disease in order to find out whether such associations
      already exist during the fourth decade of life. SETTING: A study carried out by
      the primary healthcare staff in the community of Habo in Skaraborg County in
      south-western Sweden. SUBJECTS: All men living in Habo aged 33-42 years who were
      willing to participate in the study--in total 652 men (participation rate 86%).
      MAIN OUTCOME MEASURES: Risk factors for coronary heart disease considered as
      markers of lifestyle: body-mass index as a measure of general obesity, waist-to
      hip circumference ratio as a measure of central obesity, arterial blood pressure,
      serum cholesterol concentration and serum triglyceride concentration. RESULTS:
      There were statistically significant correlations between all the factors
      analysed including anthropometric data, blood pressure and serum lipids.
      CONCLUSIONS: The results indicate associations between different risk factors at
      an early age and emphasises the need for a multifactorial view on risk as early
      as at the ages which were the focus of this study.

PMID- 7738486
TI  - Hyperinsulinaemia and decreased plasma levels of dehydroepiandrosterone sulfate
      in premenopausal women with coronary heart disease.
AB  - OBJECTIVES: The purpose of the study was to establish plasma levels of insulin,
      ovarian sex hormones and dehydroepiandrosterone sulfate (DHEA-S) and to evaluate
      their correlations with lipids in premenopausal women with angiographically
      demonstrated coronary stenosis. DESIGN: Differences in plasma levels of insulin,
      ovarian sex hormones, DHEA-S and lipids between groups were compared by analysis
      of variance. SETTING: From January 1993 until December 1993 patients were
      diagnosed in the Outpatient Clinic of the Department of Endocrinology Medical
      Centre for Postgraduate Education, Warsaw. SUBJECTS: Premenopausal women with
      normal oral glucose tolerance test (OGTT) results, with and without coronary
      stenosis were studied: 21 women after acute myocardial infarction with
      angiographically demonstrated coronary stenosis (women with CHD), and 14 women
      with chest pain, a positive exercise test without significant changes of coronary
      arteries on coronarography (women with normal coronarography, NC). The control
      group consisted of nine, healthy women with no risk factors for CHD. MAIN OUTCOME
      MEASURES: In premenopausal women with CHD, the decreased plasma level of DHEA-S
      and hyperinsulinaemia were anticipated. RESULTS: In women with CHD, the plasma
      levels of DHEA-S (926.5 +/- 83 ng mL-1) were significantly lower than those in
      women with NC (1375.7 +/- 181 ng mL-1) and in healthy controls (1984 +/- 127 ng
      mL-1), P < 0.02 and P < 0.001, respectively. The fasting insulin and insulin
      response to an OGTT in women with CHD and with NC was higher than in healthy
      subjects. A significant decrease of high-density lipoprotein (HDL) cholesterol,
      HDL-2 cholesterol and apolipoprotein A-I, and an increase of total cholesterol,
      low-density lipoprotein cholesterol C and apolipoprotein B levels in women with
      CHD compared to healthy controls were observed. A negative correlation between
      fasting insulin and the plasma levels of DHEA-S was established. CONCLUSION: In
      premenopausal women, hyperinsulinaemia and decreased DHEA-S levels may contribute
      to the development of coronary atherosclerosis.

PMID- 7738487
TI  - Treatment preferences, return visit planning and factors affecting hypertension
      practice amongst general practitioners and internal medicine specialists (the
      General Practitioner Hypertension Practice Study)
AB  - OBJECTIVES: To study clinical practice and attitudes in hypertension care amongst
      general practitioners (GPs) and hospital internal medicine specialists. DESIGN:
      Mailed case report questionnaires. SUBJECTS: Ninety GPs and 69 internal medicine
      specialists at randomly selected primary health care centres and hospital
      outpatient departments. MAIN OUTCOME MEASURES: Case-bound treatment preferences,
      treatment goals and return visit planning, and views on factors influencing
      practice. RESULTS: The participation rate was 84% and 70%, for GPs and internal
      medicine specialists, respectively. GPs more often proposed nonpharmacological
      therapy (P < 0.05), solely and as a complementary treatment, and prescribed more
      calcium antagonists (P < 0.001), whilst internal medicine specialists prescribed
      more ACE inhibitors (P < 0.001). Personal experience guides practice more than
      national consensus and economy, more so with increasing time since
      specialization. CONCLUSIONS: GPs and internal medicine specialists in Sweden
      report a hypertension practice closely related to each others' and to the
      intentions of national guidelines.

PMID- 7738488
TI  - Adverse effects of psychosocial stress on gonadal function and insulin levels in
      middle-aged males.
AB  - OBJECTIVES: To investigate the relationship between gonadal function, insulin and
      psychosocial stress in middle-aged men. DESIGN: A population-based, cross
      sectional, observational study. SETTING: Glostrup Hospital, Copenhagen, Denmark.
      SUBJECTS: Four hundred and thirty-nine males, all aged 51 years. MAIN VARIABLES:
      Body-mass index (BMI), waist-to-hip ratio (WHR), insulin, C-peptide, free
      testosterone, luteinizing hormone (LH), lipids, fibrinogen, lung function tests
      (FVC, FEV1, PEF), blood pressure, a self-administered questionnaire with
      questions on psychosocial variables, lifestyle and self-rated health. RESULTS:
      Free testosterone correlated inversely (P < 0.05) with weight, BMI, WHR, and
      fibrinogen, and positively with FEV1. An independent correlation between free
      testosterone and insulin (P < or = 0.03), but not with C-peptide, was seen after
      controlling for BMI and WHR. Subjects with low levels of free testosterone, or
      those in the lowest quintile of the distribution of the hypogonadal index (HI:
      free testosterone/LH), showed a cluster of negative psychosocial variables, and
      psychological as well as health-related problems. Furthermore, hypogonadal men
      had lower (P < 0.05) levels of FEV1, peak flow and FVC, but higher (P < 0.01)
      levels of fibrinogen and higher pulse pressure than men with normal gonadal
      function. This gradient of variables, relative to HI, was not seen for possible
      confounders like BMI, WHR, and tobacco or alcohol consumption. CONCLUSION:
      Psychosocial stress may be associated with a process of premature ageing in
      middle-aged males, corresponding to a hypogonadal state as well as to indirect
      signs of increased insulin resistance.

PMID- 7738489
TI  - The medical hierarchy and perceived influence on technical and ethical decisions.
AB  - OBJECTIVE: To investigate the influence of hierarchial position and perceived
      influence on ethical and technical decisions. DESIGN: The study was conducted as
      a postal questionnaire survey. SUBJECTS: A random sample of 329 Danish physicians
      working at departments of internal medicine and related subspecialties. Of these,
      270 (82%) returned a completed questionnaire. MAIN OUTCOME MEASURE: Self-reported
      perceived influence in discussions about technical and ethical issues in
      connection with decisions to terminate treatment for patients with terminal
      malignant illness. RESULTS: The odds ratio for perceived influence between
      consultants and house officers is 14.9 for ethical issues, 44.9 for technical
      issues, and 652.3 for questions concerning departmental policy. Gender plays no
      role, when one controls for hierarchial position. CONCLUSIONS: Hierarchial
      position is the major determinant of perceived influence on technical and ethical
      decisions. Position seem to play a larger role in technical than in ethical
      decisions.

PMID- 7738490
TI  - Cold exposure increases cyclic guanosine monophosphate in healthy women but not
      in women with Raynaud's phenomenon.
AB  - OBJECTIVE: To investigate influence of whole-body cooling on cyclic GMP (cGMP) in
      women with Raynaud's phenomenon and in healthy women. DESIGN: The study was
      performed as an open, parallel-group comparison between women with Raynaud's
      phenomenon and healthy women during the winter month of February. SETTING: The
      municipality of Vasteras (Sweden). PARTICIPANTS: The Raynaud group comprised 24
      female patients. The control group consisted of 21 healthy females. MAIN OUTCOME
      MEASURE: The venous levels of cGMP were measured on three different occasions:
      just before and after 40 min of whole-body cooling and after 20 min rest at room
      temperature (21 degrees C). RESULTS: Venous cGMP increased significantly in the
      control group after cold exposure (mean difference 0.43 pmol mL-1; 95% CI, 0.018
      0.848; t = 2.18; df = 20; P = 0.02) and remained at a high level after 20 min
      rest (mean difference 0.58 pmol mL-1; 95% CI, 0.063-1.108; t = 2.34; df = 20; P =
      0.015). In contrast, the levels of venous cGMP in the Raynaud group did not
      change significantly. The difference in increase between the two groups was
      significant (P < 0.02). The diastolic blood pressure in the Raynaud group
      increased after 40 min of whole-body cooling and was still significantly
      increased (P < 0.001) after 20 min rest at room temperature (21 degrees C).
      CONCLUSION: These results indicate that women suffering from Raynaud's phenomenon
      lack the physiological response of cGMP to cold exposure, which may explain their
      increased vasospastic response.

PMID- 7738491
TI  - Chronic fatigue syndrome: a clinical and laboratory study with a well matched
      control group.
AB  - OBJECTIVE: To investigate the relation between severity of complaints, laboratory
      data and psychological parameters in patients with chronic fatigue syndrome
      (CFS). SUBJECTS: Eighty-eight patients with CFS and 77 healthy controls matched
      for age, sex and geographical area. METHODS: Patients and controls visited our
      outpatient clinic for a detailed medical history, physical examination and
      psychological tests: Checklist Individual Strength (CIS). Beck Depression
      Inventory (BDI) and Sickness Impact Profile (SIP). Venous blood was drawn for a
      complete blood cell count, serum chemistry panel, C-reactive protein and
      serological tests on a panel of infectious agents. RESULTS: All patients
      fulfilled the criteria for CFS as described by Sharpe et al. (J R Soc Med 1991;
      84: 118-21), only 18 patients (20.5%) fulfilled the CDC criteria. The outcome of
      serum chemistry tests and haematological tests were within the normal range. No
      significant differences were found in the outcome of serological tests. Compared
      to controls, significant differences were found in the results on the CIS, the
      BDI, and the SIP. These results varied with the number of complaints (CDC
      criteria). When the number of complaints was included as the covariate in the
      analysis, there were no significant differences on fatigue severity, depression,
      and functional impairment between patients who fulfilled the CDC criteria and
      patients who did not. CONCLUSION: It is concluded that the psychological
      parameters of fatigue severity, depression and functional impairment are related
      to the clinical severity of the illness. Because the extensive panel of
      laboratory tests applied in this study did not discriminate between patients and
      controls, it was not possible to investigate a possible relation between the
      outcomes of psychological and laboratory testing.

PMID- 7738492
TI  - Analysis of the MRFIT screenees: a methodological study.
AB  - PURPOSE: To review the methods used in the many publications on the MRFIT
      screenees. METHOD: Medline was searched for articles mentioning MRFIT screenees.
      The articles were collected, abstracted, and the method section and some of the
      result section were scrutinized in detail. The statements in different articles
      regarding methods used and the presentation of results were compared. RESULT: The
      analyses of the MRFIT screenees seem to be retrospective studies of mortality and
      risk factors, where the underlying data base has been far from complete. Similar
      data are presented in slightly different fashions in several papers published in
      different scientific journals at about the same time. The control of the quality
      of underlying data has been uneven and is not discussed at all in most of the
      papers published. CONCLUSION: The often-repeated statement that the MRFIT
      screenees constitute the largest and most exact data base regarding the relation
      of risk factors to mortality in the healthy male US population has no foundation.

PMID- 7738493
TI  - Serum sialic acid concentration is elevated in IDDM especially in early diabetic
      nephropathy.
AB  - OBJECTIVES: Elevated serum sialic acid concentration is a strong predictor of
      cardiovascular mortality in non-diabetic subjects. Because patients with insulin
      dependent diabetes mellitus (IDDM) and albuminuria have a highly increased
      cardiovascular morbidity and mortality, we hypothesized that IDDM patients with
      albuminuria would have an increased concentration of serum sialic acid. DESIGN:
      Cross-sectional study. SETTING: Outpatient clinic at Steno Diabetes Centre,
      Gentofte, Denmark. SUBJECTS: Twenty-six non-diabetic controls and 74 IDDM
      patients with normoalbuminuria (urinary albumin excretion [UAE] < 30 mg 24 h-1; n
      = 37), incipient nephropathy (UAE 30-300 mg 24 h-1; n = 20) and clinical
      nephropathy (UAE > 300 mg 24 h-1; n = 17), matched for sex, age and body mass
      index (BMI). MAIN OUTCOME MEASURES: Serum sialic acid concentration, concurrent
      fasting blood glucose, glycated haemoglobin (HbA1c), serum creatinine, plasma
      fibrinogen and erythrocyte sedimentation rate. RESULTS: Normoalbuminuric patients
      had a higher serum sialic acid concentration (mmol L-1) than non-diabetic
      controls (1.83 +/- 0.24 vs. 1.67 +/- 0.26; P < 0.02). Serum sialic acid
      concentration was further increased in patients with incipient nephropathy (2.02
      +/- 0.37; P < 0.03) and in patients with clinical nephropathy (2.13 +/- 0.33; P <
      0.002) compared with normoalbuminuric IDDM patients. Serum sialic acid correlated
      strongly with plasma fibrinogen (r = 0.78; P < 0.0001) and erythrocyte
      sedimentation rate (r = 0.62; P < 0.0001). In a multiple regression analysis
      including UAE, retinopathy status, fasting blood glucose, HbA1c, mean blood
      pressure, serum creatinine, age, BMI, duration and smoking. UAE and fasting blood
      glucose were the independent variables which correlated significantly with serum
      sialic acid concentration (P < 0.0001 and P < 0.05, respectively). CONCLUSION:
      Serum sialic acid is elevated in IDDM especially in albuminuric patients. Whether
      elevated serum sialic acid is predictive for early diabetic nephropathy and
      cardiovascular disease in IDDM has to be shown in the future.

PMID- 7738494
TI  - Atrial natriuretic peptide and amyloidosis.

PMID- 7738495
TI  - Temporal location of unsignaled food deliveries: effects on conditioned
      withdrawal (inhibition) in pigeon signtracking.
AB  - Standard models of Pavlovian conditioning neglect local effects of unsignaled
      unconditioned stimuli (USs) on learning and performance. Using the approach
      withdrawal behavior of pigeons toward keylights as conditioned stimuli (CSs), the
      authors varied the specific times (5-110 s) that USs occurred before or after a
      CS. Withdrawal from a CS generally increased as the time between a US before
      and/or after the CS was lengthened. Combinations of 2 distant USs produced more
      withdrawal from the CS than either US alone, whereas combinations of a distant
      and a nearby US yielded behavior intermediate between that for either US alone.
      Postacquisition retardation tests supported similar conclusions. Based on the
      temporal isolation of CSs and USs, a tentative model was offered to summarize
      these data. The results and the model suggest that a more molecular, possibly
      perceptual approach to Pavlovian excitation and inhibition is needed.

PMID- 7738496
TI  - Forms of inhibition in animal and human learning.
AB  - Forms of inhibition were identified in human predictive learning that are
      qualitatively similar to those identified by P.C. Holland (1984) in rats. When P
      (positive) signaled the outcome and PN (N = negative) signaled the absence of the
      outcome, participants learned the discrimination, but the negative cue did not
      suppress responding to a transfer cue. Post-learning reversal training, in which
      N was followed by the outcome, did not abolish the original discrimination. These
      2 results imply a configural form of inhibition. Negative transfer, which
      indicated a 2nd, elemental form of inhibition, was observed when neither PN nor N
      were reinforced during the discrimination stage. Under these conditions, negative
      transfer and the original discrimination were both abolished by individually
      pairing N with the outcome. Empirical parallels and differences with the animal
      conditioning literature are discussed.

PMID- 7738497
TI  - Effects of context on responding during a compound stimulus.
AB  - In 4 experiments, the authors used rats to examine the strength of responding
      during a clicker-tone compound in the presence of a light, after the auditory
      stimuli had individually been paired with food in the presence of the same light.
      Experiment 1 demonstrated a higher rate of responding during the compound when
      the duration of the light was short rather than long. In Experiments 2, 3, and 4,
      the long duration light was used as a signal for food in a conditional
      discrimination involving the tone and the clicker. Responding on test trials with
      the clicker-tone compound during the light was enhanced by this treatment and
      resulted in a level of performance that was no different from that observed when
      the duration of the light was short. The results are more compatible with a
      configural than an elemental theory of associative learning.

PMID- 7738498
TI  - Supernormal conditioning.
AB  - In Experiment 1, rats received an A+AX degrees discrimination in which food was
      presented after Stimulus A by itself but not after a simultaneous compound of A
      with Stimulus X. AX was then paired with food in a 2nd stage, followed by test
      trials with A alone. Responding on the test trials with A was more vigorous than
      during a control stimulus that had been consistently paired with food. The
      remaining experiments were of similar design to Experiment 1, except that the 2nd
      stage also contained conditioning trials with X. The results from the test trials
      were essentially the same as for Experiment 1. The high level of responding
      during the test trials with Stimulus A is regarded as evidence of supernormal
      conditioning. Overall, the results are more consistent with a configural than an
      elemental theory of conditioning.

PMID- 7738499
TI  - Overshadowing in landmark learning: touch-screen studies with pigeons and humans.
AB  - Overshadowing in landmark learning was studied in pigeons and undergraduates
      using a touch-screen spatial search task. Ss searched for an unmarked goal
      presented in varied locations on a computer screen. Graphic stimuli served as
      landmarks. The effect of the presence of other landmarks on the control acquired
      by a given landmark was assessed using a design in which each S was trained with
      2 sets of landmarks. Both pigeons (Experiment 1) and humans (Experiments 2-4)
      showed evidence of learning more about a landmark that was the closest landmark
      of its set to the goal than about a landmark that was of equal distance to the
      goal but was not the closest landmark of its set. That is, control by a landmark
      was overshadowed when it occurred together with a landmark that was closer to the
      goal. Landmark effectiveness appears to depend not only on the absolute
      properties of a landmark but on relative factors. The relevance of basic
      principles of associative learning to spatial landmark learning is discussed.

PMID- 7738500
TI  - Effects of category length and strength on familiarity in recognition.
AB  - In most recognition models a decision is based on a global measure often termed
      familiarity. However, a response criterion is free to vary across lists varying
      in length and strength, making familiarity changes immeasurable. We presented a
      single list with a mixture of exemplars from many categories, so that the
      criterion would be unlikely to vary with length or strength of the category of
      the test item. False alarms rose with category length but not category strength,
      suggesting that familiarity does not change much with changes in strength of
      other items but grows when additional items are studied. The results were well
      fit by an extension of the search of associative memory (SAM) model presented by
      R. M. Shiffrin, R. Ratcliff, and S. E. Clark (1990).

PMID- 7738501
TI  - Base-rate effects in multidimensional perceptual categorization.
AB  - The optimality of human performance when category base rates differ was
      investigated in 2 multidimensional perceptual categorization tasks. All
      participants were sensitive to differences in base rate, even during their 1st
      experimental session. Nearly half of the participants learned the optimal
      decision bound by their final experimental session. Little evidence for
      conservative cutoff placement was found (i.e., an underestimation of category
      base-rate differences). In fact, participants who did not learn the optimal
      decision bound tended to use a decision bound that overestimated the base-rate
      difference. Across all conditions participants showed a clear shift toward the
      optimal decision bound with experience. These data suggest that experienced
      participants are highly sensitive to differences in category base rate. The model
      based analyses suggest that the decision-bound model of categorization (Ashby,
      1992a; Ashby & Maddox, 1993; Maddox & Ashby, 1993) provides a powerful tool for
      investigating the limits of human categorization performance.

PMID- 7738502
TI  - Decision processes in recognition memory: criterion shifts and the list-strength
      paradigm.
AB  - This article focuses on decision processes in recognition memory. It begins with
      investigation of the hypothesis that the measured criterion increases
      systematically with the memorability of old items. Three experiments using the
      list-strength paradigm, and a review of the prior literature, present results
      consistent with this hypothesis. Several psychological models of criterion
      placement are examined, generating different predictions about the relative sizes
      of criterion shifts for strong and weak items. A range model, in which criterion
      placement depends on the estimated range of the old and new distributions,
      predicts that criterion shifts should be larger for weak items; this result
      emerges in a reanalysis of prior studies. The general discussion elaborates on
      how a focus on criterion placement can explain the mirror effect (Glanzer, Adams,
      Iverson, & Kim, 1993) and provides a framework for testing Shiffrin, Ratcliff,
      and Clark's (1990) claims about why null effects of list strength occur with
      repetition.

PMID- 7738503
TI  - Attention, automaticity, and levels of representation in number processing.
AB  - Participants performed same-different judgments for pairs of numerals in 2
      conditions: numerical matching (responding "same" to pairs such as 2-TWO), or
      physical matching (responding "different" to pairs such as 2-TWO). In most cases,
      a distance effect was obtained, with the different responses being slower when
      the 2 numbers were numerically close together (e.g., 1-2) than when they were
      further apart (e.g., 1-8). This indicates that numbers were automatically
      converted mentally into quantities, even when the participants had been told to
      attend exclusively to their physical characteristics. As postulated by several
      models of number processing, (e.g., Dehaene, 1992; McCloskey, 1992) Arabic and
      verbal numerals thus appear to converge toward a common semantic representation
      of quantities. However, the present results suggest that an asemantic transcoding
      route might allow for a direct mapping of Arabic and verbal numbers, perhaps by
      means of a common phonological representation.

PMID- 7738504
TI  - Repetition priming of nonwords in young and older adults.
AB  - In 3 experiments, a pronunciation task was used to examine repetition priming of
      novel nonwords in young and older adults. The contributions of item and
      associative priming to the total repetition priming effect were assessed. In
      Experiment 1, age consistency was found in both components of repetition priming
      after 9 repetitions of nonwords. Experiment 2 established that young and older
      adults were similar in item and associative priming after as few as 2 repetitions
      of nonwords. Finally, Experiment 3 demonstrated that associative priming persists
      for at least 3 min and that it is dissociable from cued recall. The overall
      pattern of results strongly argues that elaborative processing is not necessary
      to obtain associative priming in indirect memory tasks and that young and older
      adults show similar magnitudes of associative priming.

PMID- 7738505
TI  - The role of perspective in the accessibility of goals during reading.
AB  - An implicit assumption of several causal reasoning models is that readers adopt
      the goals of a narrative's protagonist during text comprehension. In apparent
      violation of this assumption, readers participating in Experiment 1 of the
      present study drew inferences relevant to a protagonist's goal even when that
      goal was already satisfied from the perspective of the protagonist. In
      Experiments 2 and 3, participants were explicitly asked to view the text
      situation from the point of view of the protagonist. In this case, the goals of
      the reader and the protagonist should be the same. In these experiments,
      participants focused on the goals of the protagonist only when those goals had
      not been satisfied from the perspective of the protagonist. These results are
      discussed in terms of reader- and character-based perspectives and in terms of
      text characteristics that cue perspective taking.

PMID- 7738506
TI  - Backward updating of mental models during continuous reading of narratives.
AB  - Participants' ability to track the protagonist's position and surroundings,
      during continuous reading, was investigated. In Experiment 1, participants read
      passages involving either inside-outside or top-down topological relations. A
      typical story described the protagonist interacting with 1 object, which was
      either consistent or inconsistent with his or her location. The results show that
      it took longer to read the sentence in the inconsistent condition. Experiments 2
      5 used recognition probe words to test the accessibility of both consistent and
      inconsistent objects. The results show that participants did not update the
      situation model when the last sentences did not mention again any target object
      (Experiments 2 and 3). However, the mention of an object by means of an ambiguous
      pronoun triggers the updating of the situation to resolve the antecedent. The
      updating starts immediately after reading the pronoun, and the target still
      remains activated at the end of the sentence (Experiments 4 and 5). The overall
      results establish boundary conditions for mental model updating.

PMID- 7738507
TI  - Phonological computation and missing vowels: mapping lexical involvement in
      reading.
AB  - The role of assembled versus addressed phonology in reading was investigated by
      examining the size of the minimal phonological unit that is recovered in the
      reading process. Readers named words in unpointed Hebrew that had many or few
      missing vowels in their printed forms. Naming latencies were monotonically
      related to the number of missing vowels. Missing vowels had no effects on lexical
      decision latencies. These results support a strong phonological model of naming
      and suggest that even in deep orthographies, phonology is not retrieved from the
      mental lexicon as a holistic lexical unit but is initially computed by applying
      letter-to-phoneme computation rules. The partial phonological representation is
      shaped and completed through top-down activation.

PMID- 7738508
TI  - The bizarreness effect: it's not surprising, it's complex.
AB  - Higher recall of bizarre images relative to common images (the bizarreness
      effect) is consistently found when bizarreness is varied as a within-subject
      (mixed-list) variable. In Experiment 1, mixed lists, rather than the smaller
      number of bizarre sentences typically used in such lists, determined the
      occurrence of the bizarreness effect. Contrary to predictions from expectation
      violation theory, Experiments 2 and 3 showed that manipulations designed to
      augment or attenuate surprise reactions to bizarre sentences had little impact on
      the bizarreness effect. Experiments 4 and 5 indicated that mixing affected the
      degree to which participants differentially encoded order information for bizarre
      and common items. A new account of the bizarreness effect is presented that
      combines considerations of distinctiveness with the differential use of order
      information across bizarre and common items.

PMID- 7738509
TI  - Functional characteristics of the inner voice and the inner ear: single or double
      agency?
AB  - Double agency theories of short-term memory posit the functional independence of
      a phonological store (inner ear) and articulatory process (inner voice). A series
      of 5 experiments challenges this view. Articulatory suppression during retention
      of 9-item lists gives rise to a changing-state effect similar to that shown for
      irrelevant speech. Also, vocalized suppression is more disruptive than silently
      mouthed suppression, but this difference arises from vocalization itself rather
      than from any auditory feedback to which it gives rise. Class similarity between
      the to-be-remembered items and the articulatory material is not a critical
      determinant, but the effect occurs only with tests of serial order. For mouthed
      suppression, the irrelevant speech effect is only attenuated with changing-state
      suppression. Also, the presence of changing-state irrelevant speech abolishes the
      changing-state effect of articulatory suppression. Functional equivalence of
      codes from auditory, visual, and articulatory sources is claimed.

PMID- 7738510
TI  - Prior knowledge and functionally relevant features in concept learning.
AB  - Empirical learning models have typically focused on statistical aspects of
      features (e.g., cue and category validity). In general, these models do not
      address the contact between people's prior knowledge that lies outside the
      category and their experiences of the category. A variety of extensions to these
      models are examined, which combine prior knowledge with empirical learning.
      Predictions of these models were compared in 4 experiments. These studies
      contrasted the cue and category validity of features with people's prior
      knowledge about the relevance of features to the functions of novel artifacts.
      The findings suggest that the influences of knowledge and experience are more
      tightly integrated than some models would predict. Furthermore, relatively
      straightforward ways of incorporating knowledge into an empirical learning
      algorithm appear insufficient (e.g., use of knowledge to weight features by
      general relevance or to individually weight features). Other extensions to these
      models are suggested that focus on the importance of intermediary features,
      coherence, and conceptual roles.

PMID- 7738511
TI  - Object-array structure, frames of reference, and retrieval of spatial knowledge.
AB  - Experiments are reported that assessed the ability of people, without vision, to
      locate the positions of objects from imagined points of observation that are
      related to their actual position by rotational or translational components.
      Theoretical issues addressed were whether spatial relations stored in an object
      to-object system are directly retrieved or whether retrieval is mediated by a
      body-centered coordinate system, and whether body-centered access involves a
      process of imaging updating of self-position. The results, with those of Rieser
      (1989), indicate that in the case of regularly structured object arrays,
      interobject relations are directly retrieved for the translation task, but for
      the rotation task, retrieval occurs by means of a body-centered coordinate
      system, requiring imagined body rotation. For irregularly structured arrays,
      access of interobject spatial structure occurs by means of a body-centered
      coordinate system for both translation and rotation tasks, requiring imagined
      body translation or rotation. Array regularity affected retrieval of spatial
      structure in terms of global shape of interobject relations and local object
      position within global shape.

PMID- 7738512
TI  - Incilaria mucus agglutinated human erythrocytes.
AB  - The body surface mucus from the land slug, Incilaria fruhstorferi, not only
      opsonized sheep red blood cells (SRBC) and agglutinated human types A and B
      erythrocytes (HRBC) but also caused hemolysis of B type HRBC 12 h after
      agglutination. The mucus-induced hemagglutination was specifically inhibited by a
      low concentration of N-acetyl D-galactosamine (GalNAc), and all of this activity
      was completely inactivated by heating at 56 degrees C for 30 min. SDS
      polyacrylamide gel electrophoresis of water soluble fraction of the mucus showed
      that this fraction contained several proteins, the molecular mass of the main
      band being 35 KD.

PMID- 7738513
TI  - Removal of embryo-toxic ammonium from the culture medium by in situ enzymatic
      conversion to glutamate.
AB  - An enzymatic method for removing embryo-toxic ammonium from culture medium has
      been developed. Ammonium, produced by both embryo metabolism and spontaneous
      breakdown of amino acids at 37 degrees C, is transaminated by glutamate
      dehydrogenase to nontoxic glutamate. Initially, the individual components of the
      transamination reaction were titrated against mouse embryo development in vitro
      to determine embryo-safe levels. ADP, an allosteric activator of glutamate
      dehydrogenase, was found to inhibit embryo development and was therefore omitted
      from the final formulation (alpha-ketoglutarate, 0.44 mM; glutamate
      dehydrogenase, 0.375 U; NADH, 0.12 mM). It was found that 0.30 mM ammonium could
      be removed from the culture medium in situ in 3 h. In situ removal of ammonium
      significantly increases both blastocyst cell number, implantation, fetal
      development, and fetal weight after transfer. Removal of ammonium by the
      conventional method of renewing the culture medium also increased blastocyst cell
      number but did not affect postimplantation development. In conclusion, it is
      possible to alleviate the toxic effects of ammonium in vitro on pre- and
      postimplantation mouse embryo development by its transamination in situ, thereby
      facilitating the continual exposure to embryo-derived factor(s) which stimulates
      both pre- and postimplantation development.

PMID- 7738514
TI  - Androstenedione metabolism in the indifferent stage of bovine gonad development.
AB  - Suspensions of cells obtained from genital ridges and gonads of bovine embryos of
      1.0-3.4 cm in crown-rump (C-R) length were used for studies of the metabolism of
      radiolabeled exogenous steroid precursor. Tritiated androstenedione was employed
      as precursor and the final products of their metabolism were evaluated after
      separation by thin-layer chromatography. Genetic sex was determined by the
      karyotype of hepatocytes from the same embryos. The extent of conversion of
      tritiated androstenedione was higher in cells from male embryos than cells from
      female embryos. Furthermore, androstenedione was metabolized mainly to
      testosterone in male embryos. By contrast, cells obtained from female embryos
      transformed androstenedione to estrone and 17 beta-estradiol. The onset of this
      activity was observed at 1.8 cm in C-R length in males and at 2.2 cm in C-R
      length in females. In all cases, after the onset, the metabolic activity
      increased in relation to the age of the embryos. These data show that in the
      bovine embryo gonad, the activity of aromatase and 17 beta-hydroxysteroid
      dehydrogenase are present when the morphological differentiation of the gonadal
      sex has not yet been established.

PMID- 7738515
TI  - Isolation and characterization of the cDNA encoding the spiny dogfish shark
      (Squalus acanthias) form of cytochrome P450c17.
AB  - Cytochrome P450c17 is a key steroidogenic enzyme for the production of sex
      steroids in gonadal tissue and for cortisol production in adrenal tissue. This
      protein possesses two enzymatic activities. The 17 alpha-hydroxylase activity
      results in the introduction of a hydroxyl group at the 17 alpha-position. The
      resultant 17 alpha-hydroxylated, C21 pregnene is converted to a C19 androgen by
      the C17,20-lyase activity. A cDNA library was constructed from poly(A)-enriched
      mRNA isolated from spiny dogfish shark (Squalus acanthias) testis and ligated
      into EcoRI-cut lambda arms. The amplified library was screened using a bovine
      P450c17 cDNA probe and five positive clones were isolated. The described cDNA
      encompasses 23 bp of the 5'-untranslated region, a 1,527 bp open reading frame,
      and 414 bp of the 3'-untranslated region. A putative polyadenylation signal
      (AATAAA) is 18 bp from the poly(A) tail. Northern blot analysis showed a single
      transcript of 1.9 kb, thus indicating the isolated clone is a full-length cDNA.
      The deduced amino acid sequence of the shark form of P450c17 is 59% and 57%
      identical to the rainbow trout and chicken forms, respectively. The shark form is
      43% to 46% identical to mammalian forms (rat, human, mouse, bovine, and porcine).
      There are large regions of extremely high identity shared among all the forms.
      The deduced shark 17 alpha-hydroxylase protein is 509 residues in length with a
      predicted weight of 57.2 kDa. Non-steroidogenic COS cells, transfected with the
      shark P450c17 cDNA, was capable of 17 alpha-hydroxylase and C17,20-lyase
      activities using both pregnenolone and progesterone as initial substrates.

PMID- 7738516
TI  - Secretory products of bovine oviductal epithelial cells support the viability and
      motility of bovine spermatozoa in culture in vitro.
AB  - The ability of secretions from the bovine oviduct to maintain the viability and
      motility of bovine spermatozoa was investigated by incubating frozen-thawed
      spermatozoa with oviductal flushings, uterine flushings, or the medium from
      cultures of oviductal epithelial cells and endothelial cells. The flushings
      obtained from both oviducts and uteri were effective for the maintenance of the
      viability and motility of spermatozoa, irrespective of the stage of the estrous
      cycle at which they had been collected. The flushings obtained from the ampullar
      region of oviducts at the follicular phase of the estrous cycle were most
      effective for the maintenance of viability and motile activity, for example, the
      forward motion of spermatozoa. Sperm viability and motility were also maintained
      by the medium from 6-hour culture of epithelial cells obtained from oviducts at
      the follicular phase of the estrous cycle. In contrast, the medium derived from
      bovine fetal artery endothelial cells had no significant effect on sperm
      viability and motility. These results suggest that the fluids of the female
      reproductive tract, in particular, the oviductal fluids at the follicular stage,
      provide a suitable environment for the maintenance of the viability and motility
      of bovine spermatozoa. It is also suggested that secretory product(s) of
      oviductal epithelial cells may play an important role in sustaining both the
      viability and motility of spermatozoa.

PMID- 7738517
TI  - In situ detection of gonadotropin-releasing hormone (GnRH) receptor mRNA
      expression in the rat ovarian follicles.
AB  - To clarify the target cells of GnRH in the ovary, in vivo expression of ovarian
      GnRH receptor mRNA was examined histologically by in situ hybridization in
      immature rats treated with PMSG only or in combination with hCG. Strong
      hybridization signals were observed in the granulosa cells of atretic follicles.
      However, no significant signals were found in the granulosa cells of healthy
      small, preantral, or early antral follicles. Healthy Graafian and preovulatory
      follicles also showed intense signals in their mural granulosa cells, but no
      signals were detected in the cumulus oophorus cells. Corpora lutea showed only
      weak signals, but luteinizing follicles probably after atresia exhibited signals
      of moderate intensity in their luteinized and remaining granulosa cells. No
      signals were detected in the theca cells and oocytes in all the follicles.
      Interstitial cells sometimes exhibited hybridization signals of moderate
      intensity, when the cells were eosinophilic. Pretreatment with different
      combinations of gonadotropins yielded different ovarian histology, but this had
      no influence on the localization of hybridization signals. These results, showing
      that the authentic GnRH receptor mRNA was expressed in a certain cell population
      in the rat ovary, suggest that the receptor is involved in the control of various
      ovarian functions including follicular development, atresia, ovulation, and
      luteinization after ovulation and follicular atresia.

PMID- 7738518
TI  - Immunohistochemical detection of P-glycoprotein in teleost tissues using
      mammalian polyclonal and monoclonal antibodies.
AB  - Mammalian P-glycoprotein is a highly conserved 170-kD integral plasma membrane
      protein functioning as an energy-dependent efflux pump of exogenous and
      endogenous lipophilic aromatic compounds entering the cell by diffusion. In this
      study, the tissue specificities of one polyclonal (pAb) and three monoclonal
      (mAbs) antibodies to mammalian P-glycoprotein were identified in paraffin
      embedded, parasagittal whole-body sections of the guppy Poecilia reticulata.
      Polyclonal antibody mdr(Ab-1) and mAbs C219, C494, and JSB-1 demonstrated
      differential staining patterns in the following tissues: bile canaliculi in the
      liver, exocrine pancreas, lumenal surface of the intestinal epithelium, renal
      tubules, interrenal tissue, branchial blood vessels, gas gland, pseudobranch, and
      the gill transverse septa. Positive P-glycoprotein expression in P. reticulata
      correlates well with published results for homologous mammalian tissues of
      secretory and excretory function. These data indicate that one or more highly
      conserved members of the P-glycoprotein transporter family exist in a teleost
      species and can be detected using commercially available mammalian antibodies.

PMID- 7738519
TI  - Stimulation of human sperm capacitation by purified lipid transfer protein.
AB  - Lipid Transfer Protein I is recognized as a key component involved in high
      density lipoprotein metabolism. We have been studying lipid transfer in relation
      to sperm capacitation, a complex series of cell surface events required for the
      acrosome reaction and fertilization. We have previously shown that Lipid Transfer
      Protein I is present and active in the female reproductive tract. In the present
      study, we show that purified Lipid Transfer Protein I directly stimulates human
      sperm capacitation, but not the acrosome reaction, in the absence of other
      biological effectors. These results provide strong evidence for a novel role for
      Lipid Transfer Protein I and reveal, for the first time, a potent activator of
      capacitation, prior to the acrosome reaction.

PMID- 7738520
TI  - The home health care bloat.

PMID- 7738521
TI  - Working (a little) for food.

PMID- 7738522
TI  - Thyroid disease and abnormal thyroid function tests in women with eating
      disorders and depression.
AB  - Forty-two female patients with an eating disorder and major depression were
      compared with 48 female patients with major depression in a retrospective chart
      study for the prevalence of thyroid disease and laboratory thyroid function
      abnormalities in the absence of thyroid disease. Eating disorder patients, aged
      30-80 years, had a significantly higher incidence in thyroid diseases (53%) then
      those with major depression alone (17%). The incidence of thyroid disease did not
      differ between the two groups among patients aged 11-29 years. Abnormal thyroid
      screening values occurred in 40% of euthyroid eating disorder patients and 34% of
      those with major depression. While the overall prevalence of thyroid disease in
      depressed females (15%) was similar to that in the general population (10.5%),
      thyroid disease in the eating disordered/depressed patients was twice the rate
      expected (24%) in the general population. Female patients who require psychiatric
      hospitalization should be routinely evaluated for thyroid function, especially
      those diagnosed with an eating disorder and depression.

PMID- 7738523
TI  - Elevated blood lead prevalence in Florida two-year-olds.
AB  - The prevalence of blood lead values of 10 mcg/dl or higher was estimated in
      Florida two-year-olds in a population-based random sample survey. Subjects were
      chosen at random from birth certificates of children born in Florida in mid-1991.
      Parents were interviewed and children's blood specimens obtained in the summer of
      1993. Results are based on 387 subjects. Overall prevalence of elevated blood
      lead was 3.2% (95% confidence limits 2.2, 4.0), with nine children in the range
      of 10 to 14 mcg/dl and four of 15 or over. In certain subgroups, prevalence was
      higher: nonwhite 9.4% (2.9, 15.9); mother not married 8.3% (3.1, 13.5); mother on
      Medicaid 6.7% (2.5, 10.8); housing built in 1978 or before 7.1% (2.3, 11.8); yard
      dirt or dirt plus grass 10.8% (4.6, 16.9). In Florida, prevalence is much lower
      than in the nation as a whole. A screening strategy that concentrates on
      screening Medicaid-eligible children and those living in homes built before 1978
      would appear to be quite efficient and may uncover a prevalence of 7.0% or more.

PMID- 7738524
TI  - Was Julius Caesar's epilepsy due to a brain tumor?
AB  - Two thousand thirty-eight years later, in the setting of a similar care
      presentation, a physician would take a detailed history and perform a clinical
      and neurological examination. A preliminary diagnosis would be entertained and
      followed by electroencephalography and magnetic resonance of the brain with and
      without paramagnetic contrast for diagnostic confirmation. The proper medical or
      surgical treatment would then be instituted. A reconstruction of the clinical
      history of Julius Caesar (100-44 B.C.) has been attempted from available
      information from literature. Although a definite conclusion obviously cannot be
      made, a differential diagnosis provided with a tentative hypothesis is presented.
      The patient had late onset of seizures in the last two years of his life,
      headaches, personality changes. Upon reexamination of existing Julius Caesar
      iconography, busts, statues and minted coins no skull deformities have been
      noted. Identification of a skull deformity as described by Suetonius would have
      confirmed the suspicion of meningioma involving the convexity of the cerebral
      hemispheres. Meningioma or slow-growing supratentorial glioma may well have been
      responsible for this man's illness. Who knows how the course of history might
      have been changed... Probably not at all.

PMID- 7738525
TI  - Whither the PRO? Analysis of the effectiveness of three Medicare peer review
      organizations in a Florida hospital.
AB  - The objective of this retrospective study was to evaluate the effectiveness of a
      peer review organization (PRO) on patient mortality rate in a not-for-profit, 988
      bed community hospital in Florida. The number of deaths per hospital discharge
      (mortality) was compared prior to the Professional Foundation for Health Care
      (PFHC) holding the contract as the Medicare PRO (1983), during two years in which
      the PRO was fully active (1990 and 1991), during the year limited PRO activities
      were conducted (1992), and when PRO activities were again fully expanded (1993).
      All Medicare hospital discharges, including deaths, were included from January
      through May during 1983, 1990 through 1993. There was no intervention. Patient
      mortality as a determinant of PRO effectiveness was evaluated prior to the PRO,
      during a portion of the years the PFHC held the contract as the Medicare PRO, and
      an identical time period one year later with limited PRO review and again the
      following year when full reviews returned. The number of deaths did not change
      significantly. Mandated peer reviews of care to inpatient hospital Medicare
      beneficiaries did not significantly improve health care as measured by mortality.

PMID- 7738526
TI  - Third spacing is bad for health care.

PMID- 7738527
TI  - Response to Kirkpatrick et al article.

PMID- 7738528
TI  - Cost-effectiveness.

PMID- 7738529
TI  - Response to Kirkpatrick et al article.

PMID- 7738531
TI  - Middle class.

PMID- 7738530
TI  - Fraud and abuse.

PMID- 7738532
TI  - Pain control.

PMID- 7738533
TI  - Gender difference in horizontality performance before and after training.
AB  - To investigate why some individuals, especially females, fail Piaget's
      horizontality task, the author administered Piaget's horizontality task, the rod
      and frame field-dependence task, Bem's Sex Role Inventory, and a history of
      spatial activities questionnaire to 122 undergraduates. Individuals who failed
      the horizontality task were trained on this task, and after 1 month all
      participants were administered a horizontality posttest. Hierarchical regression
      analysis revealed that field dependence was related significantly to both pretest
      and posttest scores. Sex and masculine sex role concept were related to pretest
      but not to posttest scores. The implications of these findings for group
      differences in horizontality performance are discussed.

PMID- 7738534
TI  - Mothers' ratings of infant temperament: relation to neonatal latency to soothe by
      pacifier.
AB  - Latency to soothe by a pacifier in the neonatal period was assessed for 107 full
      term infants. When the infants were 9 and 12 months old, their mothers rated
      their temperament on standardized questionnaires. Correlations were computed
      between the neonatal latencies to soothe and the temperament ratings. When
      compared with neonates who soothed more quickly, neonates who took longer to
      soothe were likely to be rated at 9 months as more active, more rhythmic, more
      approachful to new situations, and more adaptable; and at 12 months as more
      approachful, more pleasant in mood, and more The results are discussed in terms
      of developmental stages and individual variability in maturation, a shared
      underlying dimension of behavior for motor activity and emotionality, and a link
      across time between objective ratings of behavior and maternal views of infant
      temperament.

PMID- 7738535
TI  - Maternal separation anxiety: relations to adult attachment representations in
      mothers of infants.
AB  - Guided primarily by attachment theory, this longitudinal study explored how adult
      mental representations of attachment relationships and memories of childhood
      experiences with parents contributed to a mother's anxiety about separation from
      her own infant. The Maternal Separation Anxiety Scale, the Adult Attachment
      Interview, and the Mother-Father-Peer Scale were administered to a sample of 49
      first-time mothers. The mothers with insecure attachment representations, when
      asked to remember details of their own childhood, reported more negative
      recollections of early parental caregiving, particularly rejection and
      discouragement of independence. When their own infants were 2 months old, these
      mothers experienced heightened levels of maternal separation anxiety. The
      findings provide theoretical and empirical support for the view that very high
      levels of maternal separation anxiety may indicate dysfunction.

PMID- 7738536
TI  - Quarrel involvement of school-aged children: gender differences, age trends, and
      school adjustment correlates.
AB  - How quarrel involvement (QI) relates to social likeability (SL) and scholastic
      attainment (SA) was investigated in a group of 201 Israeli school-aged children,
      boys and girls, from Grades 2, 4, and 6. QI as well as SL scores were obtained
      from peer ratings, and SA was rated by home-class teachers. The results indicate
      significant gender differences in QI, with boys being consistently rates as more
      involved in quarrels than girls. No overall developmental trend in QI was found.
      Very high correlations between peer ratings of QI submitted by boy raters and by
      girl raters indicate that QI was a reliably assessable personal characteristic. A
      clear inverse relation between QI and SL was found for both boys and girls from
      both cross-gender and within-gender perspectives, the only exception being a lack
      of such a relation for girls in fourth and sixth grades from the boys'
      perspective. A clear inverse relation between QI and SA was found for boys in all
      grade levels. This relation held only for girls in second grade, not for girls in
      fourth and sixth grades.

PMID- 7738537
TI  - Interaction of cis- and trans-diamminedichloroplatinum with metallothionein in
      vivo.
AB  - The properties of platinum (II) complexes to induce the biosynthesis of
      metallothionein (MT) were investigated in rabbits following injections of
      K2PtCl4, cis and trans isomers of DDP (diammine-dichloroplatinum). It was
      demonstrated that cis-DDP has an ability to induce MT specifically in the liver,
      whereas trans-DDP appears to be unable to stimulate the biosynthesis of MT in
      either the liver or the kidneys. In contrast, K2PtCl4 is effective to elevate the
      MT level in both tissues. However, all of these platinum complexes are rather
      poor stimulators for MT biosynthesis compared to cadmium and zinc compounds.
      Preinjection with Zn(NO3)2 significantly enhances the amount of Pt associated
      with the MT fractions compared to that resulting from injections with either cis-
      or trans-DDP without Zn(NO3)2 pretreatment. Metallothionein containing Pt was
      purified and identified from the liver and kidneys of rabbits after preinjections
      with Zn(NO3)2 followed by repeated injections of cis-DDP and trans-DDP,
      respectively. It was found for the first time that a relatively higher degree of
      Pt was associated with MT fractions in the case of trans-DDP treatment than that
      of cis-DDP injection. On this basis, the role of MT was discussed in relation to
      its involvement in the metabolism of cis-DDP, and the difference of the antitumor
      activity and toxicity between cis- and trans-DDP.

PMID- 7738538
TI  - 1H and 31P NMR study of speciation in systems containing ADP, Al3+, and fluoride.
AB  - It has been proposed that AlF4- can serve as a tetrahedral pseudophosphate bound
      to guanosine diphosphate (GDP) [or other nucleoside diphosphates (NDP)] in G
      protein systems. In a previous paper [D. J. Nelson and R. B. Martin, J. Inorg.
      Biochem. 43, 37 (1991)], 19F and 1H NMR were used to analyze the ternary system
      Al(3+)-NDP-F- in aqueous solutions. Ternary complexes (NDP)AlFx (with x = 1-3)
      were identified, but no (NDP)AlF4 was found. In this paper, the equilibrium
      constants for ternary complex formation that were obtained in the previous paper
      were further tested in a more extensive 1H and 31P NMR study of speciation in
      systems that contained Al3+, F-, and adenosine 5'-diphosphate (ADP). The results
      of the study are in general support of previously derived constants for ternary
      complexes and also provide support for the existence at relatively high ADP
      concentration (approximately 10 mM) of a base-stacked intermolecular dihydroxy-di
      Al3+ bridged ADP dimeric structure at an ADP to Al3+ molar ratio of 1:1. 31P NMR
      of the dimer reveals that each of the two Al3+ ions is bidentately coordinated to
      the alpha and beta phosphates of a single (but different) ADP molecule. Evidence
      is also presented for the existence at relatively low ADP concentration
      (approximately 0.5 mM) of a monomeric species in which a single Al3+ ion is
      coordinated to alpha and beta phosphates of a single ADP molecule. 1H NMR of the
      monomeric species reveals the expected "wrong-way chemical shift" of the adenine
      C8 proton upon Al3+ ion complexation to the phosphate chain.

PMID- 7738539
TI  - Reconstitution of manganese oxide cores in horse spleen and recombinant
      ferritins.
AB  - The formation of Mn(III) oxyhydroxide (MnOOH) cores within the nanoscale cavity
      of the iron storage protein ferritin has been investigated by electron microscopy
      and visible absorption spectroscopy. At pH 8.9, discrete amorphous MnOOH cores
      were formed within horse spleen apoferritin at a range of metal:protein ratios,
      as well as in ferritin molecules seeded with a small ferrihydrite nucleus.
      Analysis of the resultant core size distributions showed that the reconstitution
      of horse spleen apoferritin with Mn(II) was similar to that observed previously
      for Fe(II) reconstitution in recombinant human L-chain ferritin, suggesting that
      horse spleen apoferritin does not exhibit Mn(II) oxidase activity at pH 8.9.
      Reconstitution with MnOOH shows essentially "all-or-nothing" behavior in which
      many protein molecules remain unmineralized whilst others are loaded to maximum
      capacity. Kinetic studies showed no significant differences between horse spleen
      ferritin, recombinant H- and L-chain homopolymers, and H-chain variants
      containing site-directed modifications at the ferroxidase and putative Fe
      nucleation centers. Our results indicate that the reconstitution of ferritin with
      MnOOH cores proceeds by a nonspecific pathway. We propose that the outer surface
      of the protein inhibits the development of MnOOH nuclei in bulk solution whereas
      the inner surface is inactive, enabling nucleation and growth to proceed
      unperturbed within the cavity. One possibility is that differences in the general
      polyelectrolyte properties of these two surfaces, rather than site-specific
      charges, account for the "Janus" behavior of the molecule. A similar mechanism
      might also increase the specificity of iron oxide mineralization in ferritins
      that lack ferroxidase centers.

PMID- 7738540
TI  - Interaction of tetra-mu-acetatodirhodium(II) with human serum albumin.
AB  - The interaction of Rh2(OAc)4 with human serum albumin (HSA) has been studied by
      absorption difference spectroscopy, CD spectroscopy, and quantitative
      precipitating HSA-antibody test. Our results demonstrate that this rhodium
      complex reacts easily with HSA at several ratios of reagents. The Rh atoms are
      coordinated to protein molecules via the imidazole rings of His residues. The
      structural studies have shown the conformational change of HSA modified by
      rhodium. Rhodium binding lowers the helicity of the native protein between 8 to
      18% depending upon the molar ratios (from 1:1 to 10:1). Denaturation measurements
      of free HSA and HSA in the presence of dirhodium(II) acetate complex with 8-M
      urea followed by CD spectroscopy, suggest that rhodium affects the secondary
      protein structure and might stabilize HSA against denaturing agents. 8-M urea
      caused the unfolding of the native HSA secondary structure by about 40% and the
      structure of Rh(OAc)4-HSA by about 10%. The modification of native HSA by rhodium
      causes its decreased ability to precipitate with HSA antibodies. The decrease of
      antigenic properties can be connected with the unfolding of the antigen
      structure, which brings about perturbation of complementarity of the antigen
      antibody reactive sites.

PMID- 7738541
TI  - Platinum binding to metallothionein. Analysis of circular dichroism spectra of
      complexes formed between metallothionein and platinum from cis- and trans
      diamminedichloroplatinum.
AB  - The first observation of the circular dichroism (CD) spectral features of
      platinum-saturated metallothionein, Pt7MT, is presented. It is characterized by
      two intensive bands with maxima at 235 nm (-) and 255 nm (+). Properties of the
      reactions of cis- and trans-diamminedichloroplatinum (DDP) with rabbit liver MT
      have been studied by monitoring the CD spectral changes. The overall rate of the
      reaction between trans-DDP and MT is determined to be significantly faster than
      that for cis-DDP and MT. The stepwise incorporation of Pt into Zn7MT resulted in
      a nonsystemic changes in the CD spectral envelope. These data argue that Pt(II)
      replaces Zn(II) in ZnMT in a nonspecific, "distributed" manner across both
      domains, because the onset of clustering was observed after 5 mol equiv of Pt was
      bound. A dynamic mechanism has been proposed in which the reaction proceeds via
      the formation of an intermediate, RS-Pt (NH3)2-SR. As it is converted to the
      product, the ammine ligands are lost very slowly, especially in the case of cis
      DDP, because of the strong requirement of Pt for square planar coordination,
      which comprises the rate-limiting step.

PMID- 7738542
TI  - Neuropsychiatric aspects of HIV infection.

PMID- 7738543
TI  - Papaver somniferum (opium poppy).

PMID- 7738544
TI  - Imaging of the spinal cord.

PMID- 7738545
TI  - Disorders of higher cortical function.

PMID- 7738546
TI  - Prognostic factors for survival in multiple sclerosis: a longitudinal, population
      based study in More and Romsdal, Norway.
AB  - A longitudinal, population based study of life expectancy in multiple sclerosis
      was performed in the county of More and Romsdal, Norway during the period 1950
      84. A total of 251 patients with multiple sclerosis (110 men, 141 women, mean age
      at onset of disease 33.6 years) were included. The mean follow up time was 18.1
      years. At the end of the study period 70 patients had died. Fifty four (77.1%) of
      these had multiple sclerosis as the underlying or contributing cause of death on
      the death certificates. Young age at onset, initial remitting clinical course,
      and the presence of sensory symptoms at onset were significantly associated with
      longer survival.

PMID- 7738547
TI  - Vascular ataxic hemiparesis: a re-evaluation.
AB  - Ataxic hemiparesis is commonly considered as one of the "typical" lacunar
      syndromes. Using the prospective stroke registries from Lausanne and Besancon,
      100 patients were selected consecutively (73% men, 27% women; age 64.7 (SD 13.6)
      years) with a first stroke and ataxic hemiparesis (hemiparesis or pyramidal signs
      and ipsilateral incoordination without sensory loss). Brain CT or MRI was
      performed on all patients. A primary haemorrhage was present in 5%, an infarct in
      72%, isolated leukoaraiosis in 9%, and no apparent abnormality in 14%. The
      locations of lesions were the internal capsule (39%), pons (19%), thalamus (13%),
      corona radiata (13%), lentiform nucleus (8%), cerebellum (superior cerebellar
      artery territory) (4%), and frontal cortex (anterior cerebral artery territory)
      (4%). The clinical features of ataxic hemiparesis with different locations were
      almost identical. Only minor associated signs allowed the localisation of the
      lesions (paraesthesiae with a lesion in the thalamus; nystagmus or dysarthria
      with a cerebellar or pontine location). Crural paresis with homolateral ataxia
      was seen only with cortical paramedian frontal lesions. Presumed hypertensive
      small artery disease was not always found, but was still the leading cause of
      stroke, being present in 59% of the patients and in 62% of those with small deep
      infarcts. A potential source of embolism (arterial or cardiac) was found in one
      fourth of the patients. Therefore no definite association can be made between
      ataxic hemiparesis and lacunar infarction. In particular, so called uncommon
      lesion locations may not be rare. After extensive investigations a diagnosis of
      lacunar infarct can be retained in only slightly more than half of the cases.

PMID- 7738548
TI  - Acute hemiconcern: a right anterior parietotemporal syndrome.
AB  - Three patients developed a striking visual and motor behaviour in the acute phase
      of a stroke involving the territory of the right anterior parietal artery
      (postcentral gyrus, parts or upper and middle temporal gyri, anterior part of
      inferior parietal gyrus, and supramarginal gyrus). The patients concentrated on
      the left side of their bodies, looking at it for long periods and relentlessly
      rubbing, touching, pinching, pressing, lifting, and manipulating parts of the
      left arm, trunk, and leg with their right hand or foot. They all had severe loss
      of elementary sensation on the left (touch, pain, temperature, vibration,
      position). The behaviour was not associated with overinterest in the left
      hemispace apart from their own bodies. It lasted no more than a few days,
      disappearing when left sided sensation improved. The findings suggest an
      association between sensory dysfunction and this "acute hemiconcern". None of 13
      patients with a mirror infarct in the left hemisphere and none of 38 patients
      with acute hemisensory loss due to thalamic capsular or brainstem stroke showed
      hemiconcern behaviour. This behaviour may result from a feeling of strangeness
      critically associated with hemisensory loss without hemispatial neglect, due to
      involvement of the right anterior parietotemporal region.

PMID- 7738549
TI  - Damage to cerebellocortical pathways after closed head injury: a behavioural and
      magnetic resonance imaging study.
AB  - The objective was to investigate the anatomical substrate of ataxia seen after
      severe head injury. Five patients were recruited from present and former
      inpatients at Rivermead Rehabilitation Centre. All patients had had a closed head
      injury and all had cerebellar type ataxia. Four normal controls were also
      studied. Brain MRI, clinical examination, computer based recording, and analysis
      of visuomotor tracking were carried out. Focal damage was found in the superior
      cerebellar peduncle in all five ataxic patients. The patients' tracking movements
      showed profound tremor, and unusual reliance on visual feedback. Ataxia seen
      after severe head injury can arise from damage to the superior cerebellar
      peduncle, which may interfere with the cerebellocortical circuits involved in
      coordinated movement.

PMID- 7738550
TI  - Magnetic resonance imaging in partial epilepsy: additional abnormalities shown
      with the fluid attenuated inversion recovery (FLAIR) pulse sequence.
AB  - Thirty six patients with a history of partial epilepsy had MRI of the brain
      performed with conventional T1 and T2 weighted pulse sequences as well as the
      fluid attenuated inversion recovery (FLAIR) sequence. Abnormalities were found in
      20 cases (56%), in whom there were 25 lesions or groups of lesions. Twenty four
      of these lesions were more conspicuous with the FLAIR sequence than with any of
      the conventional sequences. In 11 of these 20 cases, lesions thought to be of
      aetiological importance were only seen with the FLAIR sequence. In eight this was
      a solitary lesion. In the other three, an additional and apparently significant
      lesion (or lesions) was only seen with the FLAIR sequence when another lesion had
      been identified with both conventional and FLAIR sequences. The 11 additional
      lesions or groups of lesions were seen in the hippocampus, amygdala, cortex, or
      subcortical and periventricular regions. No lesion was found with any pulse
      sequence in 16 (44%) of the original group of 36 patients. In the eight cases
      where a lesion was seen only with the FLAIR sequence, localisation was concordant
      with the electroclinical features. Two of the eight patients with solitary
      lesions seen only on the FLAIR sequence underwent surgery, after which there was
      pathological confirmation of the abnormality identified with imaging. In one
      patient with a congenital cavernoma, the primary lesion was best seen with a
      contrast enhanced T1 weighted spin echo sequence. In this selected series, the
      FLAIR sequence increased the yield of MRI examinations of the brain by 30%.

PMID- 7738551
TI  - Comparison of rates of infection of two methods of emergency ventricular
      drainage.
AB  - The rates of infection of two methods of external ventricular drainage in use at
      Atkinson Morley's Hospital--namely, (a) percutaneous drainage with Rickham
      reservoirs and (b) tunnelled ventriculostomies--were compared in this
      retrospective review. Percutaneous drainage of CSF with Rickham reservoirs was
      associated with a 27% rate of infection as identified by positive microbiological
      cultures; tunnelled ventriculostomy catheters had a 10% infection rate. The
      difference in the infection rate between the two methods was statistically
      significant (P < 0.015). Other variables examined, including the age and sex of
      the patients and the reasons for ventricular drainage, were not associated with
      an increased rate of infection. Most infections from either method were caused by
      a coagulase negative staphylococcus. The average duration of ventricular drainage
      before identification of positive cultures was 5.7 days for Rickham reservoirs
      and 6.0 days for ventriculostomies.

PMID- 7738552
TI  - Intraventricular recombinant tissue plasminogen activator for lysis of
      intraventricular haemorrhage.
AB  - A prospective series of 20 patients with moderate to severe intraventricular
      haemorrhage (IVH) was studied for the effect of intraventricular administration
      of recombinant tissue plasminogen activator (rt-PA) on reduction of haematoma
      volume and prognosis. On the day of haemorrhage ventriculostomy was performed and
      2 to 5 mg of rt-PA were injected via the external ventricular drainage, followed
      by drainage closure for two hours. In 14 patients rt-PA treatment was repeated.
      Computed tomography showed complete clot lysis or substantial reduction of
      intraventricular haematoma volume in 19 patients within 96 hours; the clearance
      of the third and fourth ventricle preceded the clearance of the lateral
      ventricles. Decrease of ventricular enlargement was seen in all but one patient
      with initial ventricular dilatation. Increase of haematoma volume and ventricular
      size was found in one patient. Outcome was minor or no neurological deficit in
      nine patients, disabling neurological deficit in six patients, and vegetative
      status in four patients. One patient did not survive the IVH. Intraventricular
      treatment with rt-PA seems effective in rapid lysis of intraventricular haematoma
      and normalisation of impaired CSF circulation. This treatment may contribute to
      an improvement in prognosis of moderate to severe IVH.

PMID- 7738553
TI  - Hypofrontality revisited: a high resolution single photon emission computed
      tomography study in schizophrenia.
AB  - Hypofrontality or reduced activity in the prefrontal cortex, measured as reduced
      frontal perfusion or glucose uptake, has gained the status of an established
      finding in the medical literature on schizophrenia. Many relevant studies,
      however, have potential sources of bias, such as small subject numbers, or
      unreliable performance of activation tasks by the patients during the scanning
      procedure. Seventy patients with non-affective and non-organic psychoses were
      recruited--most qualifying for DSM III-R schizophrenia or schizophreniform
      psychosis (n = 60)--together with 20 healthy volunteers. They underwent single
      photon emission computed tomography with 99mTc-exametazime, carried out at rest.
      Tracer uptake was normalised to the occipital cortex. Group differences in tracer
      uptake were predicted in anterior regions of interest (prefrontal cortex and
      mesial frontal/cingulate cortex). Actively psychotic (including schizophrenic)
      patients not taking any drugs showed increased uptake in the prefrontal cortex.
      Reduced tracer uptake occurred in the mesial frontal cortex of schizophrenic
      patients, particularly if they were taking drugs. Relatively increased prefrontal
      tracer uptake associated with relatively decreased mesial frontal uptake
      characterised the patients in comparison with the controls. Generalised
      hypofrontality is, therefore, not a feature of schizophrenic patients at rest
      whether taking drugs or not.

PMID- 7738554
TI  - Meta-analysis of corpus callosum size in schizophrenia.
AB  - Studies with MRI have shown differences in corpus callosum size between
      schizophrenic patients and controls. Most have found that the corpus callosum is
      smaller in schizophrenic patients, but in only a minority was this finding
      statistically significant, perhaps due to small sample sizes. Therefore a meta
      analysis of 11 published studies of corpus callosum morphology in schizophrenia
      was conducted to ascertain whether there was a significant difference in corpus
      callosum size between schizophrenic patients and normal controls. These studies
      combined comprised 313 patients and 281 controls. Measures of corpus callosum
      midsagittal area, length, and corpus callosum area:brain area ratio were used in
      the meta-analysis. There was overall a statistically significant reduction in
      corpus callosum area in schizophrenic patients compared with controls (P < 0.02).
      Differences between patients and controls in measures of corpus callosum: brain
      area and corpus callosum length were not statistically significant. Age and
      corpus callosum area were related in both patients and controls. The influences
      on the corpus callosum of overall alterations of brain size, sex, handedness, and
      psychiatric illness in general remains to be determined.

PMID- 7738555
TI  - Incidence of sudden unexpected death in an adult outpatient cohort with epilepsy
      at a tertiary referral centre.
AB  - Overall mortality, incidence of sudden unexpected death, and cause of death were
      determined in 601 adult outpatients with epilepsy at a tertiary referral centre.
      The patients were followed up from 1990 to 30 June 1993. There were 24 deaths
      among the 601 patients (1849 patient years) with a standardised mortality ratio
      of 5.1 (95% confidence interval 3.3-7.6) of which 14 were related to epilepsy.
      Underlying disease of which epilepsy was a symptom accounted for four deaths
      only. An incidence of sudden deaths (including seizure related) was of the order
      of 1:200/year. In conclusion, excess mortality in chronic epilepsy is more likely
      to be related to the epilepsy itself than to underlying pathology. The relatively
      high incidence of sudden deaths found in this hospital based cohort has important
      implications for patient management.

PMID- 7738556
TI  - Outcome of post-traumatic unawareness persisting for more than a month.
AB  - From 1986 to the end of 1991, 19 patients with persisting post-traumatic
      unawareness were admitted for rehabilitation. Criteria for admission were head
      trauma, Glasgow coma scale score < or = 8 points, and at least a one month
      duration of unawareness. Out of 19 patients, 12 patients (63%) regained
      consciousness, 11 patients (58%) within the first year and one patient (5%)
      within the second year. The mean duration of unawareness in the patients who
      recovered consciousness was 190 (range 62-440) days. In the recovery group,
      according to the Glasgow outcome scale, seven out of 12 patients (58%) were
      moderately disabled and five (42%) were severely disabled at the moment of
      discharge from rehabilitation. All the 12 patients who regained consciousness
      live with their families, and none had to be kept in an institution. The data
      confirm that awakening from post-traumatic unawareness is possible after a long
      period. Therefore, post-traumatic unawareness persisting for more than a month
      should not be considered an irreversible condition, because an outcome that might
      be regarded by some as being acceptable is possible even in patients with very
      severe brain damage.

PMID- 7738557
TI  - Multiphasic disseminated encephalomyelitis presenting as alternating hemiplegia.
AB  - Two cases of alternating hemiparesis are reported, one in a black Sudanese woman,
      the other in a Saudi man, who had two episodes of alternating hemiparesis
      separated in time by six and three years respectively. Based on the typical
      appearance of the MRI and the results of brain biopsy, the diagnosis of
      multiphasic disseminated encephalomyelitis was made rather than that of multiple
      sclerosis. This entity is also differentiated from recurrent disseminated
      encephalomyelitis, where the relapses are symptomatically stereotyped although
      the appearance of the MRI is similar and in which new lesions do not occur.
      Because of the unusual appearance of these MRI lesions, brain biopsy is often
      performed but recognising their relevance should obviate that need.

PMID- 7738558
TI  - Focal conduction block in compression neuropathy of the proximal sciatic nerve.
AB  - Direct percutaneous stimulation of the proximal sciatic nerve with a high voltage
      electrical stimulator was given to a patient with acute sciatic compression
      neuropathy. Results clearly showed a focal conduction block at the sciatic notch,
      which could not be precisely localised and quantified by conventional
      electrodiagnostic methods.

PMID- 7738559
TI  - Bilateral pallidostriatal necrosis caused by a wasp sting: a clinical and
      pathological study.
AB  - A previously healthy man developed an acute encephalopathy with coma after a
      single wasp sting on his chin. Brain CT showed bilateral pallidostriatal radio
      lucencies. He died 72 hours after the sting with no evidence of primary
      cardiorespiratory failure or allergic reaction. Pathological findings were
      bilateral pallidostriatal necrosis and diffuse neuronal damage in the frontal,
      temporal, and parietal cortex. The neurotoxic effect of the poison, together with
      a hypersensitivity are the most likely explanations for this unusual
      encephalopathy.

PMID- 7738560
TI  - Extracerebral absorption of near infrared light influences the detection of
      increased cerebral oxygenation monitored by near infrared spectroscopy.
AB  - The detection of increased cerebral oxygenation secondary to cerebral hyperaemia,
      induced by hypercapnia has been studied in anaesthetised patients using a near
      infrared, reflectance mode, cerebral oxygenation monitor (Invos 3100 Somanetics,
      Troy, Michigan, USA). Two studies were performed, with and without a pneumatic
      scalp tourniquet, to distinguish between extracranial and intracranial changes in
      tissue oxygenation. In the control study a mean increase in end tidal CO2 of 23.1
      mm Hg was accompanied by a mean increase in middle cerebral artery flow velocity
      of 116%. Regional cerebral oxygen saturation (rSO2) measured transcutaneously in
      the frontal distribution of the middle cerebral artery increased significantly
      from 70.5% to 74.6% (p = 0.001). During the second study with a scalp tourniquet
      inflated to maintain the extracranial tissues in a state of stable ischaemia a
      mean increase in end tidal CO2 of 22.3 mm Hg was accompanied by a mean increase
      in middle cerebral artery flow velocity of 121%. The change in rSO2 from 62.6% to
      64.5% was not significant (p = 0.085). There was no correlation between the
      change in middle cerebral artery flow velocity and rSO2 in the control or scalp
      ischaemia group. This study shows that the Invos 3100 monitor is sensitive to
      tissue oxygenation but does not reliably detect changes in cerebral oxygenation
      as a result of profound cerebral hyperaemia. The contribution of extracerebral
      tissue to the attenuation of near infrared light and the lack of spatial
      resolution remain major problems to be overcome before this or other near
      infrared spectroscopy instruments can be introduced into clinical practice.

PMID- 7738561
TI  - Electrophysiological study of diaphragmatic myoclonus.
AB  - This is the first reported detailed electrophysiological study of diaphragmatic
      myoclonus. An 86 year old woman had rapid, intermittent epigastric pulsations.
      Neurological examination and imaging studies of the brain and spinal cord were
      normal. Needle EMG showed rhythmic contractions of the diaphragm and external
      intercostal muscles at 4 to 5 Hz. These contractions were often associated with
      suppression of normal breathing and were capable of maintaining adequate
      ventilation. Both diaphragms were involved but showed considerable variability in
      their relative latencies. Automated interference pattern analysis suggested a
      change in recruitment order, with selective activation of large phrenic
      motoneurons. The supraspinal mechanisms mediating diaphragmatic myoclonus are
      different from that of voluntary and involuntary rhythmic breathing, and seem to
      be unrelated to palatal myoclonus. The generator source is likely related to
      respiratory centres in the rostral medulla.

PMID- 7738562
TI  - Sleep abnormalities in traumatic apallic syndrome.
AB  - Sleep patterns in 10 patients with traumatic apallic syndrome were studied,
      together with 10 healthy controls matched for sex and age. All patients underwent
      neurological examination, brain CT, and polysomnographic recording within six
      months (mean 99 (SD 45) range 47-180 days) from the onset of symptoms. Clinical
      follow up was performed six months after enrollment in the study. Sleep patterns
      were recorded in nine out of 10 patients. In the tenth patient there was no
      rhythm resembling physiological sleep. This patient was the only one who remained
      in a persistent vegetative state and died before the six month follow up. The
      severity of neurological deficit at follow up was significantly related to the
      duration of coma. There was no significant difference between patients and
      controls with respect to sleep architecture. The time spent awake after sleep
      onset was longer in patients than controls. Our data highlight the presence of
      sleep fragmentation in traumatic apallic syndrome, which might be due to changes
      in brain structures responsible for sleep maintenance. The absence of sleep-wake
      cycles might indicate a poor outcome.

PMID- 7738563
TI  - Exacerbation of postural tremor with emergence of parkinsonism after treatment
      with neuroleptic drugs.
AB  - Neuroleptic medication in three patients with prior isolated postural arm tremor
      led to a conspicuous deterioration; the postural tremor increased in amplitude,
      tremor appeared at rest, and other signs of mild parkinsonism developed.
      Withdrawal of neuroleptic drugs led to improvement in tremor and disappearance of
      parkinsonism. Positron emission tomography showed no reduction in uptake of
      [18F]dopa into nigrostriatal terminals suggesting that these patients did not
      have Parkinson's disease. Neuroleptic drugs can convert postural essential arm
      tremor into that characteristic of Parkinson's disease in patients with no
      evident nigrostriatal lesion.

PMID- 7738564
TI  - Headache at stroke onset: the Lausanne Stroke Registry.
AB  - Within 12 hours of stroke onset 2506 patients with first ever stroke admitted to
      the Lausanne Stroke Registry were questioned about headache. Eighteen per cent of
      the patients reported headache, 14% with anterior circulation stroke and 29% with
      posterior circulation stroke (p < 0.001). Headache was reported by 16% of the
      patients with infarct and 36% of those with haemorrhage (p < 0.001). The
      prevalence of headache was 9% with lacunar infarct, 15% with middle cerebral
      artery territory infarct, 37% with infratentorial haemorrhage, and 36% with
      supratentorial haemorrhage. The most common topography of pain was frontal (41%),
      followed by diffuse headache (27%; p < 0.001). Diffuse (41%) or occipital (30%)
      headache was particularly frequent with posterior circulation stroke, whereas
      frontal headache was associated with anterior circulation stroke (51%; p <
      0.001). Headache in stroke may be explained in part by involvement of blood
      vessels (acute distention or distortion) and mechanical (stretch of haemorrhage)
      stimulation of intracranial nociceptive afferents. Stroke due to dissection was
      strongly associated with headache (p < 0.001), whereas embolic (cardiac, artery
      to artery) stroke was more common without headache (p < 0.001), emphasising the
      role of extracranial v intracranial arteries in the genesis of headache at stroke
      onset. Moreover, dual trigeminal-vascular and cervical-vascular system
      involvement in causing headache may explain the lack of correspondence with the
      "rules of referral" in up to 38% of the cases.

PMID- 7738565
TI  - Mendenhall's syndrome: clues to the aetiology of human diabetic neuropathy.
AB  - The pathogenesis of human diabetic neuropathy remains unclear. Mendenhall's
      syndrome is characterised by a mutation in the insulin receptor gene with
      consequent lifelong uncontrolled hyperglycaemia. The sural nerve biopsy from a
      patient with Mendenhall's syndrome showed a gross loss of myelinated fibres that
      was comparable with the degree of fibre loss in a case matched diabetic patient
      with established neuropathy. The biopsy from the patient with Mendenhall's
      syndrome showed only a very mild degree of microangiopathy, however, which failed
      to relate to the degree of nerve fibre loss and also did not compare with the
      advanced degree of microangiopathy seen in the diabetic patient. Thus
      hyperglycaemia itself did not result in appreciable microangiopathy. Furthermore
      the presence of severe neuropathy without advanced microangiopathy suggests an
      important and independent role for metabolic factors in the pathogenesis of
      neuropathy.

PMID- 7738566
TI  - Molecular diagnostic analysis for Huntington's disease: a prospective evaluation.
AB  - The availability of mutation analysis for the CAG repeat expansion associated
      with Huntington's disease has prompted clinicians in various specialties to
      request testing of samples from patients displaying clinical features that might
      be attributable to Huntington's disease. A series of 38 cases presenting with
      clinical features thought possibly to be due to Huntington's disease were
      analysed prospectively. In 53% of such cases presenting initially with chorea and
      62.5% with psychiatric symptoms an expansion was identified, a considerable lower
      proportion than found in previous series where the diagnosis was considered
      definite on clinical and genetic grounds. Mutation analysis is likely to be of
      considerable value in the diagnosis of Huntington's disease, especially where the
      family history in previous generations is inadequate or apparently negative.

PMID- 7738567
TI  - Shared delusions of doubles.
AB  - This is the first report of two partners in a folie a deux situation manifesting
      identical Capgras delusions. It is postulated that the Capgras syndrome developed
      as a result of interaction between a dominant patient with primarily paranoid
      psychopathology and a submissive one with primarily organic dysfunction. The
      submissive "neuro-organic" partner experienced a non-delusional misidentification
      that acquired a delusional component and developed into the Capgras syndrome as a
      result of elaboration by the dominant paranoid partner, who subsequently
      "imposed" the Capgras delusion on the submissive partner. The submissive patient,
      and, to a lesser extent the dominant patient, had evidence of organic cerebral
      dysfunction.

PMID- 7738568
TI  - Changes in metabolism of cerebral glucose after stereotactic leukotomy for
      refractory obsessive-compulsive disorder: a case report.
AB  - Brain glucose metabolism was investigated with PET and [18F]fluorodeoxyglucose,
      before and after a bifrontal stereotactic leukotomy in a 37 year old woman with
      refractory obsessive-compulsive disorder. A bilateral decrease in glucose
      metabolism was found in the orbital frontal cortex after psychosurgery. Glucose
      metabolism was decreased to a lesser degree in Brodmann's area 25, in the
      thalamus, and in the caudate nucleus. Clinical improvement in obsessive
      compulsive disorder after stereotactic tractotomy seems to be associated with
      metabolic changes in the brain, in particular, in the orbital part of the frontal
      lobe.

PMID- 7738569
TI  - An unusual cause for diplopia: acquired Brown's syndrome.

PMID- 7738570
TI  - Bilateral optic neuritis after hepatitis A.

PMID- 7738571
TI  - Sumatriptan and daily headache.

PMID- 7738572
TI  - Unilateral hypotonic seizures successfully diagnosed by ictal SPECT with
      technetium-99m-HMPAO in a patient with a brain tumour.

PMID- 7738573
TI  - Cervical extradural abscess complicating discitis and associated disc prolapse,
      secondary to a long line infection.

PMID- 7738574
TI  - Successful treatment of intractable tardive dyskinesia with botulinum toxin.

PMID- 7738575
TI  - Hypersomnolence in myotonic dystrophy: demonstration of sleep onset REM sleep.

PMID- 7738576
TI  - Increase in adenosine metabolites in human cerebrospinal fluid after status
      epilepticus.

PMID- 7738577
TI  - Bilateral cavernous sinus thrombosis causing Korsakoff's amnesic syndrome.

PMID- 7738578
TI  - Hearing loss as a false localising sign in raised intracranial pressure.

PMID- 7738579
TI  - Bromate intoxication with polyneuropathy.

PMID- 7738580
TI  - Embolism across the circle of Willis.

PMID- 7738581
TI  - Elementary visual hallucinations in migraine and epilepsy.

PMID- 7738582
TI  - Antiganglioside antibodies in the CSF of patients with motor neuron diseases and
      Guillain-Barre syndrome.

PMID- 7738583
TI  - Post-traumatic syringomyelia.

PMID- 7738584
TI  - Three decades of normal pressure hydrocephalus: are we wiser now?

PMID- 7738585
TI  - Verbal fluency in cortical and subcortical dementia.

PMID- 7738586
TI  - Jarisch-Herxheimer reaction in a patient with neurosyphilis: non-convulsive
      status epilepticus?

PMID- 7738587
TI  - Neuroimaging looks to the future.

PMID- 7738588
TI  - Modulation of p36 gene expression in human neuronal cells.
AB  - p36 is a calcium/lipid-binding phosphoprotein that is expressed at high levels in
      proliferating and transformed cells, and at low levels in terminally
      differentiated cells, such as CNS neurons. The calcium-dependent binding to
      membrane phospholipids, and its capacity to interact with intermediate filament
      proteins suggest that p36 may be involved in the transduction of extracellular
      signals. The present work examines p36 gene expression in the mature CNS, primary
      primitive neuroectodermal tumors (PNETs), and transformed PNET cell lines. p36
      immunoreactivity was not observed in normal adult human brain, but low levels of
      the protein were detected by Western blot analysis. Following acute anoxic
      cerebral injury, the mean levels of p36 protein were elevated two-fold, and
      injured neurons exhibited increased p36 immunoreactivity. This phenomenon was
      likely to have been mediated by post-transcriptional mechanisms since there was
      no corresponding change in the level p36 mRNA. p36 immunoreactivity was detected
      in 8 of 9 primary PNETs, and in 3 of 3 neurofilament-expressing PNET cell lines.
      The levels of p36 protein in PNET cell lines were 5-fold higher than in adult
      human brain tissue. Although p36 gene expression was generally high in
      proliferating PNET cells, the levels of p36 mRNA and protein were not strictly
      correlated with DNA synthesis. Instead, p36 gene expression was modulated in both
      proliferating and non-proliferating PNET cell cultures by treatment with 50
      mIU/ml of insulin, 100 mM ethanol, or 5 microM retinoic acid. The frequent
      discordances observed experimentally and in vivo between p36 mRNA and p36 protein
      expression suggest that the steady-state levels of p36 protein in neuronal cells
      may be regulated primarily by post-transcriptional mechanisms.

PMID- 7738589
TI  - Expression of glial fibrillary acidic protein in areas of focal cerebral ischemia
      accompanies neuronal expression of 72-kDa heat shock protein.
AB  - We examined the astrocytic GFAP and neuronal HSP-72 responses to transient middle
      cerebral artery (MCA) occlusion in the rat. Three groups of rats (n = 79) were
      studied: (1) fixed duration of MCA occlusion (120 min) and variable durations of
      reperfusion (0.5, 3, 6, 9, 12, 24, 48, 96 and 168 h); (2) variable durations of
      MCA occlusion (10, 20, 30, 60, 90, and 120 min) and a fixed duration of
      reperfusion (48 h); and (3) controls: sham operated rats and normal rats. Coronal
      sections from each brain were reacted with appropriate antibodies to GFAP and HSP
      72 and stained with H&E for evaluation of cellular response to ischemia. Our data
      show that after MCA occlusion: (1) GFAP expression was found in the boundary zone
      to the infarct or in areas of selective incomplete ischemic necrosis; (2) GFAP
      expression was localized to the same areas where neurons express HSP-72 and are
      destined to survive the ischemic insult; and (3) HSP-72 expression was not found
      in astrocytes in any of the experimental groups. These studies suggest that after
      transient focal ischemia in the rat: areas where both GFAP and HSP-72 expression
      are lost are destined to become necrotic, even though cells may appear
      morphologically intact in the H&E preparations, and expression of GFAP and HSP-72
      reflects astrocytic and neuronal viability, respectively.

PMID- 7738590
TI  - Effect of thyroxine on the development of somatosensory and visual evoked
      potentials in the rat.
AB  - The thyroid hormone thyroxine (T4), administered post-natally to neonatal rats,
      has been shown to accelerate development of auditory function, as expressed by
      auditory nerve-brainstem evoked responses. This study investigated whether this
      earlier development was also reflected in other sensory modalities. Rat pups were
      injected with T4 from the day of birth for 10 consecutive days. Somatosensory
      evoked potentials, both from the cortex and from sub-cortical structures, and
      flash-elicited visual evoked potentials (VEP), were recorded at various ages up
      to 3 months. The recordings were compared with those from control rats from the
      same litters. Only a minimal difference was found between the experimental and
      control groups, the most significant being in the VEP at age 12 days, by which
      time the eyes of most of the experimental rats had opened, which was not the case
      for the majority of control rats. This difference disappeared with eye-opening in
      the control rats. Although T4 is known to affect myelinization and synaptic
      transmission in developing rat brain, this apparently only minimally affects the
      functioning of the brain as expressed by evoked potentials, both in the short and
      long term. The main effect of neonatal hyperthyroidism in these rats appeared to
      be accelerated development of the end organ (the eye and the ear).

PMID- 7738591
TI  - Polarographic analyses of subsarcolemmal and intermyofibrillar mitochondria from
      rat skeletal and cardiac muscle.
AB  - We report the polarographic analysis of subsarcolemmal and intermyofibrillar
      mitochondria from rat skeletal and cardiac muscle, in order to detect possible
      biochemical and functional differences. Electron microscopic observation of
      isolated mitochondria showed normal aspect, with intact membranes. Respiratory
      control rate with different substrates and state 3 activity did not show
      differences between subsarcolemmal and intermyofibrillar mitochondria in skeletal
      muscle and heart.

PMID- 7738593
TI  - Shoulder-arm pain from cervical bands and scalene muscle anomalies.
AB  - Fourteen patients were identified with (1) pain and sensory changes in a brachial
      plexus distribution, (2) aggravation of pain with use of the affected extremity,
      and (3) pain on palpation over the brachial plexus. All patients had minimal or
      no intrinsic hand muscle atrophy. Only one patient had cervical ribs. Nerve
      conduction studies were normal, and electromyography (EMG) showed mild chronic
      neuropathic changes in 2 patients. None of the patients responded to conservative
      therapy over a prolonged period (7-12 months). A compressive brachial plexopathy
      from abnormally attached or enlarged scalene muscles that affected both upper and
      lower trunks of the brachial plexus was found at surgery in all patients. In 13
      patients, at least one fibrous band compressed the lower trunk of the brachial
      plexus. Therefore, neurogenic thoracic outlet syndrome can occur from cervical
      bands and scalene muscle anomalies without intrinsic hand muscle atrophy,
      cervical ribs, enlarged C7 transverse processes, or EMG abnormalities.

PMID- 7738592
TI  - Destruction of the cholinergic basal forebrain using immunotoxin to rat NGF
      receptor: modeling the cholinergic degeneration of Alzheimer's disease.
AB  - Degeneration of cholinergic neurons in the basal forebrain (CBF) is a prominent
      neuropathological feature of Alzheimer's disease and is thought responsible for
      some cognitive deficits seen in patients. An animal model of pure CBF
      degeneration would be valuable for analysis of the function of these neurons and
      testing therapeutic strategies. CBF neurons express receptors for nerve growth
      factor. In order to selectively destroy these neurons, we developed an
      immunotoxin using monoclonal antibody (192 IgG) to rat NGF receptor (p75NGFr)
      armed with the ribosome inactivating protein, saporin. In vitro 192-saporin was
      highly toxic to neurons expressing p75NGFr. Intraventricular injections of 192
      saporin destroyed the CBF and impaired passive avoidance learning. These results
      indicate that 192-saporin treated rats can be used to model a key feature of
      Alzheimer's disease and that anti-neuronal immunotoxins are a powerful approach
      to selective neural lesioning.

PMID- 7738594
TI  - Differentiation of embolic and thrombotic middle cerebral artery occlusion using
      ultrasonic carotid flow velocity analysis.
AB  - The purpose of this study was to determine the value of Duplex ultrasound of the
      carotid arteries in the differentiation of embolic from thrombotic middle
      cerebral artery (MCA) occlusion. We report here the results of carotid Duplex
      ultrasound study from 164 patients with acute ischemic stroke. Flow velocity and
      diameter were measured in bilateral common carotid arteries (CCA). The end
      diastolic flow velocity (Ved) and the pulsatility index (PI) were calculated from
      Doppler waves. The PI is an index of peripheral vascular resistance. We compared
      the relationship between percent carotid stenosis and percent decrease in Ved.
      The patients studied could be classified into three groups using ultrasound
      parameters. Group I was characterized by > 30% decrease in Ved and < 80% carotid
      stenosis, group II by < 30% decrease in Ved and < 80% carotid stenosis, and group
      III by > 30% decrease in Ved and > 80% carotid stenosis. All 23 patients in group
      I had embolic MCA stem occlusion. 28 out of 115 patients in group II had
      thrombotic MCA stem occlusions. All 26 patients in group III had internal carotid
      artery occlusion or severe stenosis. Ved was markedly reduced in group I and
      group III compared to group II (p < 0.01). PI in the affected artery was
      increased in groups I and III (p < 0.01). Embolic occlusion was characterized by
      > 30% decrease in Ved in the absence of > 80% carotid stenosis, and an increase
      in PI. The results indicate that these two conditions can be differentiated using
      Duplex ultrasound in carotid arteries.

PMID- 7738595
TI  - Sympathetic skin responses evoked by magnetic stimulation of the neck.
AB  - We studied sympathetic skin responses (SSRs) following magnetic stimulation of
      the neck in 40 normal subjects and 54 patients with neurological diseases and
      active sweat gland densities (ASGDs) at the foot induced by pilocarpine in 39
      patients. SSRs at the hand following magnetic stimulation showed the lowest
      coefficients of variability of the latencies and amplitudes in eight consecutive
      responses compared with SSRs following other types of stimuli (electrical and
      auditory stimulation, and deep inspiration) in 12 normal subjects. Fourteen of 38
      patients with neuropathies (37%) showed the presence of SSRs after magnetic
      stimulation, but not after median nerve stimulation, although SSRs to magnetic
      stimulation corresponded with those to nerve stimulation in all patients with
      multiple sclerosis or multiple system atrophy. These results suggest that the
      absence of SSRs after nerve stimulation in patients with neuropathies may be due
      to abnormalities of the peripheral sensory afferent fibers. ASGDs significantly
      correlated with SSRs at the foot following magnetic stimulation, but not with
      those following nerve stimulation in patients with neuropathies. Magnetic
      stimulation of the neck is the highly reproducible method of evoking SSRs because
      this technique is able to produce strong sensory afferent inputs proximally.
      Furthermore, SSRs following magnetic stimulation, little influenced by sensory
      afferent fiber involvement, are very useful for evaluating the postganglionic
      sympathetic function in patients with neuropathies.

PMID- 7738596
TI  - Gating of somatosensory evoked responses during active finger movements
      magnetoencephalographic studies.
AB  - The "gating" effects caused by active finger movements on somatosensory evoked
      magnetic fields (SEFs) following stimulation of the median nerve were examined in
      normal subjects. The effects of the interfering stimulus were best demonstrated
      by subtracting the "interference" wave forms from the "control" wave forms to
      derive the "difference" wave form. The short-latency cortical deflections, N20m
      P20m, P30m-N30m and P25m-N35m were significantly attenuated with no latency
      changes. In contrast, the following middle-latency deflections, the N40m-P40m and
      the P60m-N60m were clearly changed in terms of latency and duration by the
      interference. The D30m-U30m and the U60m-D60m in the "difference" wave form were
      derived from these interference changes. It is considered that the gating effects
      on all deflections took place in the hemisphere contralateral to the stimulated
      median nerve, because all of the equivalent current dipoles (ECDs) of the short-
      and the middle-latency deflections in the "control", "interference" and
      "difference" wave forms were located there. The gating effects on the short
      latency deflections were suggested to be due to the interactions between the
      neurons in areas 1 and 3b, which were activated by sensory inputs from cutaneous
      mechanoreceptors, and the neurons in area 3a which were activated by sensory
      inputs from the muscle spindles. The gating effects on the middle-latency
      deflections may mainly be due to the excitations of neurons in area 4 caused by
      either continuous movement-related activities or by sensory inputs spreading from
      the sensory cortex.

PMID- 7738597
TI  - Levodopa-induced local cerebral blood flow changes in Parkinson's disease and
      related disorders.
AB  - Local cerebral blood flow (CBF) in the steady state and after intravenous
      administration of levodopa (1 mg/kg) was measured by xenon-enhanced computed
      tomography in patients with Parkinson's disease (PD, n = 16), progressive
      supranuclear palsy (PSP, n = 6), olivopontocerebellar atrophy (OPCA, n = 5), and
      arteriosclerotic parkinsonism (AP, n = 7). Three patterns of local CBF changes
      following levodopa were observed: (1) diffuse CBF increases, especially in
      striatum and thalamus, as found in patients with PD; (2) no significant changes
      in CBF, as in patients with OPCA and AP; and (3) CBF reductions in basal ganglia
      and thalamus, as seen in patients with PSP. The CBF increases after levodopa in
      PD may be secondary to metabolic activation of the nigrostriatal dopaminergic
      system. The poor CBF responses in patients with OPCA, AP, and PSP appeared to
      reflect degeneration of the dopaminergic neurons and dopamine receptors to
      various degrees. The CBF increases, especially in striatum and thalamus, tended
      to be greater (not significant) among responders to oral levodopa therapy.
      Levodopa-induced CBF measurements may be useful for the differential diagnosis of
      parkinsonian syndromes of various etiologies, but are not necessarily sufficient
      for predicting outcomes of long-term levodopa therapy.

PMID- 7738598
TI  - Concurrence of Alzheimer's disease, Parkinson's disease, diffuse Lewy body
      disease, and amyotrophic lateral sclerosis.
AB  - A 71-year-old man developed signs of progressive dementia, followed by
      extrapyramidal and motor neuron disease symptoms, which led to death in 6 years.
      Neuropathological examination revealed neuritic plaques, neurofibrillary tangles,
      and Lewy bodies in the substantia nigra and neocortex. Atrophy and gliosis with
      intraneuronal ubiquitin inclusions were present in the anterior horns of the
      spinal cord. Overlapping of Alzheimer's disease, Parkinson's disease, diffuse
      Lewy body disease and amyotrophic lateral sclerosis is rare and can increase our
      understanding of the process of neurodegeneration.

PMID- 7738599
TI  - Myotonic dystrophy with alveolar hypoventilation and hypersomnia: a
      clinicopathological study.
AB  - We present a case of myotonic dystrophy accompanied by alveolar hypoventilation
      and hypersomnia. Case history, pulmonary function tests, polygraphic recording,
      and multiple sleep latency test, concomitant with a restrictive ventilatory
      abnormality, suggested a central origin of alveolar hypoventilation and
      hypersomnia in our case. The most significant neuropathological findings were in
      the tegmentum of the brain stem. Severe neuronal loss and gliosis were observed
      in the midbrain and pontine raphe, particularly in dorsal raphe nucleus and
      superior central nucleus. Pontine and medullary reticular formation also showed a
      marked cell loss and fibrillary gliosis. The alveolar hypoventilation and the
      hypersomnia in our case may be attributed to these morphological abnormalities,
      and would appear to be central in nature.

PMID- 7738600
TI  - Hyperventilation alternating with apnea in neuroleptic malignant syndrome
      associated with metoclopramide and cisapride.

PMID- 7738601
TI  - A shape-based machine learning tool for drug design.
AB  - Building predictive models for iterative drug design in the absence of a known
      target protein structure is an important challenge. We present a novel technique,
      Compass, that removes a major obstacle to accurate prediction by automatically
      selecting conformations and alignments of molecules without the benefit of a
      characterized active site. The technique combines explicit representation of
      molecular shape with neural network learning methods to produce highly predictive
      models, even across chemically distinct classes of molecules. We apply the method
      to predicting human perception of musk odor and show how the resulting models can
      provide graphical guidance for chemical modifications.

PMID- 7738602
TI  - Extended electron distributions applied to the molecular mechanics of some
      intermolecular interactions.
AB  - Extended electron distributions (XEDs) have been added to the molecular mechanics
      Coulombic term and applied to a selection of intermolecular interactions. The
      results from this approach have been compared with the commonly used atom-centred
      charges and more rigorous AM1-derived natural atom orbital point densities. The
      use of XEDs generally improves the simulation of experimental and ab initio
      results over the other two charge allocations and corrects geometries in those
      cases for which the others yield wrong results.

PMID- 7738603
TI  - Prediction of the binding sites of huperzine A in acetylcholinesterase by docking
      studies.
AB  - We have performed docking studies with the SYSDOC program on acetylcholinesterase
      (AChE) to predict the binding sites in AChE of huperzine A (HA), which is a
      potent and selective, reversible inhibitor of AChE. The unique aspects of our
      docking studies include the following: (i) Molecular flexibility of the guest and
      the host is taken into account, which permits both to change their conformations
      upon binding. (ii) The binding energy is evaluated by a sum of energies of
      steric, electrostatic and hydrogen bonding interactions. In the energy
      calculation no grid approximation is used, and all hydrogen atoms of the system
      are treated explicitly. (iii) The energy of cation-pi interactions between the
      guest and the host, which is important in the binding of AChE, is included in the
      calculated binding energy. (iv) Docking is performed in all regions of the host's
      binding cavity. Based on our docking studies and the pharmacological results
      reported for HA and its analogs, we predict that HA binds to the bottom of the
      binding cavity of AChE (the gorge) with its ammonium group interacting with
      Trp84, Phe330, Glu199 and Asp72 (catalytic site) and to the opening of the gorge
      with its ammonium group partially interacting with Trp279 (peripheral site). At
      the catalytic site, three partially overlapping subsites of HA were identified
      which might provide a dynamic view of binding of HA to the catalytic site.

PMID- 7738604
TI  - Prediction of the binding site of 1-benzyl-4-[(5,6-dimethoxy-1-indanon-2
      yl)methyl]piperidine in acetylcholinesterase by docking studies with the SYSDOC
      program.
AB  - In the preceding paper we reported on a docking study with the SYSDOC program for
      predicting the binding sites of huperzine A in acetylcholinesterase (AChE) [Pang,
      Y.-P. and Kozikowski, A.P., J. Comput.-Aided Mol. Design, 8 (1994) 669]. Here we
      present a prediction of the binding sites of 1-benzyl-4-[(5,6-dimethoxy-1-indanon
      2-yl)methyl]piperidine (E2020) in AChE by the same method. E2020 is one of the
      most potent and selective reversible inhibitors of AChE, and this molecule has
      puzzled researchers, partly due to its flexible structure, in understanding how
      it binds to AChE. Based on the results of docking 1320 different conformers of
      E2020 into 69 different conformers of AChE and on the pharmacological data
      reported for E2020 and its analogs, we predict that both the R- and the S-isomer
      of E2020 span the whole binding cavity of AChE, with the ammonium group
      interacting mainly with Trp84, Phe330 and Asp72, the phenyl group interacting
      mainly with Trp84 and Phe330, and the indanone moiety interacting mainly with
      Tyr70 and Trp279. The topography of the calculated E2020 binding sites provides
      insights into understanding the high potency of E2020 in the inhibition of AChE
      and provides hints as to possible structural modifications for identifying
      improved AChE inhibitors as potential therapeutics for the palliative treatment
      of Alzheimer's disease.

PMID- 7738605
TI  - Local elevation: a method for improving the searching properties of molecular
      dynamics simulation.
AB  - The concept of memory has been introduced into a molecular dynamics algorithm.
      This was done so as to persuade a molecular system to visit new areas of
      conformational space rather than be confined to a small number of low-energy
      regions. The method is demonstrated on a simple model system and the 11-residue
      cyclic peptide cyclosporin A. For comparison, calculations were also performed
      using simulated temperature annealing and a potential energy annealing scheme.
      Although the method can only be applied to systems with a small number of degrees
      of freedom, it offers the chance to generate a multitude of different low-energy
      structures, where other methods only give a single one or few. This is clearly
      important in problems such as drug design, where one is interested in the
      conformational spread of a system.

PMID- 7738606
TI  - Pharmacophore refinement of gpIIb/IIIa antagonists based on comparative studies
      of antiadhesive cyclic and acyclic RGD peptides.
AB  - Structurally guided design approaches to low-molecular-weight platelet
      aggregation antagonists addressing the platelet-associated heterodimeric cell
      surface receptor gpIIb/IIIa rely on comparative studies of an ensemble of
      conformationally and biologically characterized compounds, since no high
      resolution structure of the receptor system is available. We report a classical
      indirect and comparative pharmacophore refinement approach based on a series of
      small cyclic Arg-Gly-Asp (RGD) peptides as gpIIb/IIIa-fibrinogen interaction
      antagonists. These peptides have previously been investigated as potent and
      selective tumor cell adhesion inhibitors. The definition of geometrical
      descriptors classifying the RGD peptide conformations and their subsequent
      analysis over selected RGD- and RXD-containing protein structures allows for a
      correlation of distinct structural features for platelet aggregation inhibition.
      An almost parallel alignment of the Arg and Asp side chains was identified by a
      vector analysis as being present in all active cyclic hexa- and pentapeptides.
      This orientation is induced mainly by the constraint of backbone cyclization and
      is not of any covalent tripeptide-inherent origin, which was rationalized by a
      500 ps high-energy MD simulation of a sequentially related linear model peptide.
      The incorporation of the recognition tripeptide Arg-Gly-Asp into the cyclic
      peptide templates acted as a filter mechanism, restricting the otherwise free
      torsional relation of both side chains to a parallel orientation. Based on the
      derived results, several detailed features of the receptor binding site could be
      deduced in terms of receptor complementarity. These findings should govern the
      design of next-generation compounds with enhanced activities. Furthermore, the
      complementary stereochemical characteristics of the substrate can be used as
      boundary conditions for pseudoreceptor modelling studies that are capable of
      reconstructing a hypothetical binding pocket, qualitatively resembling the steric
      and electronic demands of gpIIb/IIIa. It is interesting to note that these
      features provide clear differentiation to requirements for inhibition of alpha v
      beta 3 substrate binding. This can account for the extremely high selectivity and
      activity of some of our constrained peptides for either the alpha IIb beta 3 or
      the alpha v beta 3 receptor.

PMID- 7738607
TI  - Finding potential DNA-binding compounds by using molecular shape.
AB  - For the first time a general shape-search docking algorithm (DOCK) has been
      applied to the minor and major grooves of A-, B- and Z-type DNA dodecamers and to
      an intercalation site in a B-DNA-type hexamer. Both experimentally and
      theoretically derived geometries for the various DNA fragments were used. The
      DOCK searches were carried out on a subset of the Cambridge Crystallographic
      Database, consisting of almost 10,000 molecules. One of the molecules that scored
      best in terms of the DOCK algorithm was CC-1065, a potent antitumor agent known
      to (covalently) bind the AT-rich parts of the minor groove of B-DNA. Several
      known DNA-binding agents also scored highly. Molecules with shapes complementary
      to A-, B- and Z-type DNA were indicated by DOCK. In addition, compounds were
      extracted from the database that might be selective for the GC-rich regions of
      the minor groove of B-DNA. Many of the compounds in the present study may serve
      as a starting point for further molecular design of novel DNA-binding ligands.

PMID- 7738608
TI  - Different approaches toward an automatic structural alignment of drug molecules:
      applications to sterol mimics, thrombin and thermolysin inhibitors.
AB  - A relative comparison of the binding properties of different drug molecules
      requires their mutual superposition with respect to various alignment criteria.
      In order to validate the results of different alignment methods, the
      crystallographically observed binding geometries of ligands in the pocket of a
      common protein receptor have been used. The alignment function in the program
      SEAL that calculates the mutual superposition of molecules has been optimized
      with respect to these references. Across the reference data set, alignments could
      be produced that show mean rms deviations of approximately 1 A compared to the
      experimental situation. For structures with obvious skeletal similarities a
      multiple-flexible fit, linking common pharmacophoric groups by virtual springs,
      has been incorporated into the molecular mechanics program MOMO. In order to
      combine conformational searching with comparative alignments, the optimized SEAL
      approach has been applied to sets of conformers generated by MIMUMBA, a program
      for conformational analysis. Multiple-flexible fits have been calculated for
      inhibitors of ergosterol biosynthesis. Sets of different thrombin and thermolysin
      inhibitors have been conformationally analyzed and subsequently aligned by a
      combined MIMUMBA/SEAL approach. Since for these examples crystallographic data on
      their mutual alignment are available, an objective assessment of the computed
      results could be performed. Among the generated conformers, one geometry could be
      selected for the thrombin and thermolysin inhibitors that approached reasonably
      well the experimentally observed alignment.

PMID- 7738609
TI  - A phase I trial on the ethics of phase I trials.

PMID- 7738610
TI  - Molecular markers and stem-cell transplants: are they made for each other?

PMID- 7738611
TI  - Attitudes and behaviors on physician-assisted death: a study of Michigan
      oncologists.
AB  - PURPOSE: To ascertain the attitudes of oncologists toward physician-assisted
      death, ie, physician-assisted suicide and active euthanasia, as well as their
      experiences with these activities and their opinions toward their legalization.
      METHODS: A survey was mailed to all practicing 250 oncologists in the state of
      Michigan, with subsequent development of psychometric scales and their
      correlation with self-reported behaviors in physician-assisted death. RESULTS:
      Analysis revealed five distinct, meaningful factors regarding approval or
      disapproval of physician-assisted death. These factors reflected global attitudes
      toward physician-assisted death, passive euthanasia, philosophical prohibitions
      toward physician-assisted death, concerns of legal consequences with physician
      assisted death, and attitudes that physician-assisted death could be avoided with
      better end-of-life care (alpha = .94, .74, .76, .87, and .84, respectively). High
      levels of therapy withdrawal were reported (81%), with significant reservations
      toward assisted suicide and active euthanasia, although reported participation in
      such actions was noteworthy (18% and 4%, respectively). The scales reflecting
      global and philosophical attitudes correlated with several attitudes and
      behaviors toward physician-assisted death (P < .001). Legislation that would
      allow physician-assisted death was favored by 20.8% of respondents. CONCLUSION:
      Although they have reservations about physician-assisted death, significant
      numbers of oncologists are willing to consider such actions should they become
      legal. Given the substantial number of physicians who report that they have
      already participated in physician-assisted death, these findings may help better
      understand the attitudes that motivate physician behaviors toward assisted death.

PMID- 7738612
TI  - Perceptions of cancer patients and their physicians involved in phase I trials.
AB  - PURPOSE: In an attempt to understand some of the complex issues related to the
      participation of cancer patients in phase I trials, and the perceptions of
      patients toward these trials, we conducted a pilot survey study of 30 cancer
      patients who had given informed consent to participate in a phase I trial at our
      institution. Concurrently, the oncologists identified by the surveyed patients as
      responsible for their care were surveyed as well. PATIENTS AND METHODS: Twenty
      seven of 30 consecutive patients agreed to and completed the survey. Patients
      were surveyed before they received any investigational agents. Eighteen
      oncologists participated in this survey study. RESULTS: Eighty-five percent of
      patients decided to participate in a phase I trial for reasons of possible
      therapeutic benefit, 11% because of advice/trust of physicians, and 4% because of
      family pressures. Ninety-three percent said that they understood all (33%) or
      most (60%) of the information provided about the trials in which they had decided
      to participate. Only 33% were able to state the purpose of the trial in which
      they were participating, with patients able to state the purpose of phase I
      trials being more educated (P = .01). Surveyed oncologists had wide-ranging
      beliefs regarding expectations of possible benefits and toxicities for their
      patients participating in phase I trials. CONCLUSION: Cancer patients who
      participate in phase I trials are strongly motivated by the hope of therapeutic
      benefit. Altruistic feelings appear to have a limited and inconsequential role in
      motivating patients to participate in these trials. Cancer patients who
      participate in phase I trials appear to have an adequate self-perceived knowledge
      of the risks of investigational agents. However, only a minority of patients
      appear to have an adequate understanding of the purpose of phase I trials as dose
      escalation/dose-determination studies.

PMID- 7738613
TI  - Significance of molecular marker-positive cells after autologous peripheral-blood
      stem-cell transplantation for non-Hodgkin's lymphoma.
AB  - PURPOSE: To evaluate the significance of molecular marker-positive cells in a
      cohort of non-Hodgkin's lymphoma (NHL) patients undergoing high-dose chemotherapy
      and autologous peripheral-blood stem-cell transplantation (PBSCT). PATIENTS AND
      METHODS: Twenty-eight PBSC transplants have been performed in 24 patients with
      poor-prognosis NHL. Molecular analysis of the t(14;18) (q32;q21) translocation
      (bcl-2/immunoglobulin [Ig] heavy-chain joining locus [JH] fusion) or antigen
      receptor gene rearrangements was performed to determine the presence of lymphoma
      cells at presentation, in PBSC harvests, and before and after autologous PBSCT.
      Kaplan-Meier estimates of survival and Cox regression analyses were used to test
      the effect of bone marrow involvement, tumor-cell contamination of PBSCs, disease
      stage, and chemotherapy sensitivity at transplantation, and presence of marker
      positive cells post-PBSCT on disease-free and overall survival. RESULTS: Thirteen
      of 24 patients (54%) are alive following PBSCT at a median follow-up time of 654
      days (range, 193 to 1,908). Nine patients are in complete remission (CR) at day
      216 to 1,799 (median, 805) and four are alive following relapse (day 440, 573,
      1,188, and 1,908). Eleven patients (46%) have died: three of transplant-related
      complications at day 0, 1, and 13, and eight of recurrent disease (day 132 to
      1,330; median, 451). Longitudinal marker studies post-PBSCT showed that of 16
      relapse events, 13 (81%) were positive for the lymphoma marker at or before
      clinically documented relapse. Marker studies became negative post-PBSCT in nine
      of nine patients who entered and remained in CR. Disease-free survival (DFS) was
      significantly shortened in patients in whom marker-positive cells were detected
      in serial samples posttransplantation (P = .006). Cox regression analysis showed
      that patients in this group had a 24 times higher risk of relapse (P = .03).
      CONCLUSION: The results show that the reappearance or persistence of marker
      positive cells after autologous PBSCT is strongly associated with relapse.

PMID- 7738614
TI  - Phase I/II study incorporating intravenous hydroxyurea into high-dose
      chemotherapy for patients with primary refractory or relapsed and refractory
      intermediate-grade and high-grade malignant lymphoma.
AB  - PURPOSE: A phase I/II study was performed to evaluate the incorporation of
      hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL).
      PATIENTS AND METHODS: Thirty-eight patients with primary refractory and
      refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day 
      8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150
      mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous
      hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose
      escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion.
      When the IV formulation was not available, 17 patients were given 18 g/m2 of HU
      orally in divided doses every 6 hours over the same 72-hour period. RESULTS: The
      dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was
      mucositis. Endotracheal intubation was necessary to protect the airway in two
      thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV
      BCHE, one of 21) died with nonresponding or progressive disease and, at least in
      part, from the complications of the high-dose chemotherapy. Seventeen patients
      (45%) achieved complete remission (CR). More patients treated with IV BCHE
      achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1,
      chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain
      disease-free as of January 31, 1994, with a minimum follow-up time of 3 years.
      The lower mortality and higher response rate with IV BCHE translated into a
      significantly superior probability of progression-free survival (PFS) (33% at 4
      year v 12% for oral BCHE; P = .048, log-rank test). CONCLUSION: High-dose BCHE is
      effective treatment for primary refractory and refractory relapsed NHL.
      Continuous IV HU appears to be less toxic and more effective than intermittent
      oral HU in this regimen.

PMID- 7738615
TI  - Allogeneic bone marrow transplantation for refractory and recurrent low-grade
      lymphoma: the case for aggressive management.
AB  - PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in
      recurrent low-grade lymphoma. PATIENTS AND METHODS: Between 1989 and 1994, 10
      patients with chemotherapy-refractory and recurrent low-grade lymphoma were
      treated with myeloablative therapy and allogeneic BMT. All patients had poor
      prognostic features and had been extensively pretreated. RESULTS: Eight patients
      achieved a complete remission and none have relapsed at a median follow-up time
      of 816 days (range, 346 to 1,865). Two patients died of early complications. The
      actuarial survival and failure-free survival rates are both 80% +/- 12.6%. For
      surviving patients, the duration of the current remission exceeds that of any
      previous remission achieved. CONCLUSION: These results compare favorably with
      those for autologous BMT. Allogeneic BMT offers considerable promise for the
      treatment of patients with poor-prognosis low-grade lymphoma. Its role should be
      further defined in prospective studies.

PMID- 7738616
TI  - Association of BK virus with failure of prophylaxis against hemorrhagic cystitis
      following bone marrow transplantation.
AB  - PURPOSE: Hemorrhagic cystitis (HC) after bone marrow transplantation (BMT) has
      been ascribed to cyclophosphamide metabolites. HC has also been associated with
      excretion of the BK type of polyomavirus. The relative contributions of
      cyclophosphamide metabolites and BK virus in the development of HC following BMT
      are unknown. PATIENTS AND METHODS: We conducted a randomized trial to compare
      mesna with forced diuresis for prophylaxis against HC in 147 BMT recipients. We
      studied the association of BK virus with HC in 95 consecutive BMT recipients by
      prospectively monitoring urinary excretion of BK virus using polymerase chain
      reaction amplification of viral gene sequences. RESULTS: HC occurred in 37 of 147
      (25.2%) transplant recipients. The incidence of HC was similar in patients given
      mesna (26.8%, 19 of 71) or forced diuresis (23.7%, 18 of 76), and in recipients
      of allogeneic (27.2%, 18 of 64) or autologous marrow (22.9%, 19 of 83). The
      incidence of HC was unrelated to primary disease, preparative regimen, or
      occurrence of graft-versus-host disease (GVHD). Excretion of BK virus was
      demonstrated in 50 of 95 patients (52.6%); 38 patients (40%) had persistent BK
      viruria (> or = two consecutive positive samples). HC occurred in 19 of 38
      patients (50%) with persistent BK viruria, in one of 12 (8.3%) with only a single
      urine sample positive for BK virus, and in none of 45 who did not excrete BK
      virus (P < .0001). Shedding of BK virus also had a strong temporal correlation
      with onset of HC (r = .95). CONCLUSION: Mesna and forced diuresis are equally
      effective in abrogating the urothelial toxicity of preparative regimens for BMT.
      Since HC after BMT is virtually always associated with persistent BK viruria,
      strategies aimed at the prevention or elimination of viruria in BK seropositive
      recipients are warranted.

PMID- 7738617
TI  - Combination therapy with interferon alfa-2a and interleukin-2 for the treatment
      of metastatic cancer.
AB  - PURPOSE: Here we report the long-term follow-up evaluation of a phase I/II study
      of toxicity and response of combination interferon alfa-2a (IFN alpha) and
      interleukin-2 (IL-2) in patients with metastatic cancer. PATIENTS AND METHODS:
      From November 1987 through October 1990, 189 patients were treated with 379
      courses. IFN alpha (3 x 10(6) U/m2) was administered three times per day as an
      intravenous (IV) bolus with IV IL-2 2.6 x 10(6) IU/m2 (six patients, group 1),
      7.8 x 10(6) IU/m2 (32 patients, group 2), or 11.7 x 10(6) IU/m2 (26 patients,
      group 3). Subsequently, IFN alpha dose was escalated to 6 x 10(6) U/m2 plus IL-2
      11.7 x 10(6) IU/m2 (22 patients, group 4). Two further dosage schedules of IL-2
      were tested at 7.8 x 10(6) IU/m2 (29 patients, group 5) and 15.6 x 10(6) IU/m2
      (74 patients, group 6); however, because of IFN alpha-related toxicity, these two
      groups received IFN alpha once per day (6 x 10(6) U/m2). A treatment course
      consisted of two cycles (maximum, 15 doses per cycle) separated by a 10-day
      interval. RESULTS: All patients were assessable for response: 82 patients had
      melanoma, 75 renal cell carcinoma (RCC), and 16 colorectal cancer. There were two
      treatment-related deaths. The objective response rate was 23% (43 patients).
      Response rates were 17%, 19%, 19%, 32%, 41%, and 16%, respectively, for groups 1
      through 6. Ten responses are still ongoing (nine in RCC patients) at 57 to 74
      months, and 21 patients are alive, for an overall 5-year survival rate of 11%.
      The median potential follow-up period was 65 months. Although a significantly
      higher response rate was noted for group 4 (highest dose of IFN alpha three times
      per day), no benefit for survival and increased toxicity were noted in this
      group. CONCLUSION: Based on these findings, we conclude that further studies of
      this combination treatment are not warranted.

PMID- 7738618
TI  - Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy
      of breast cancer.
AB  - PURPOSE: Decisions concerning the use of hormone therapy to treat metastatic
      breast cancer are made on the basis of the presence of estrogen receptor (ER).
      Despite the presence of ER, half of patients will not respond to hormone
      treatment. The purpose of this study was to determine the effect of
      overexpression of HER-2/neu on the response to hormone therapy. PATIENTS AND
      METHODS: Sera from 300 metastatic breast cancer patients with ER-positive (ER+),
      ER status unknown, or ER-/progesterone receptor-positive (PR+) randomized to
      receive second-line hormone therapy with either megestrol acetate or fadrozole
      were evaluated. An enzyme immunoassay (EIA) specific for the extracellular domain
      of the c-erbB-2 (HER-2/neu) oncogene product was used to detect serum levels.
      RESULTS: Fifty-eight patients (19.3%) had elevated serum c-erbB-2 protein levels,
      using a selected cut-point of 30 U/mL. The response rate (complete responses
      [CRs] plus partial responses [PRs] plus stable disease [S]) to endocrine therapy
      was 40.9% in 242 patients with low serum c-erbB-2 levels and only 20.7% in 58
      patients with elevated serum c-erbB-2 levels (P = .004). The median duration of
      treatment response was longer in the group with low serum c-erbB-2 levels (15.5
      months) compared with the group with elevated serum c-erbB-2 levels (11.6
      months). Survival was also significantly shorter in patients with elevated serum
      c-erbB-2 levels (P < .0001). CONCLUSION: Patients with ER+/c-erbB-2+ metastatic
      breast cancer are less likely to respond to hormone treatment than ER+/c-erbB-2-
      patients. Their survival duration is also shorter.

PMID- 7738619
TI  - Phase I and pharmacologic study of the alkylating agent modulator novobiocin in
      combination with high-dose chemotherapy for the treatment of metastatic breast
      cancer.
AB  - PURPOSE: Resistance to alkylators may potentially be overcome by drugs that
      inhibits DNA repair, thus improving the efficacy of high-dose chemotherapy. This
      trial was performed to determine if novobiocin, an agent that inhibits DNA
      repair, could be given with high-dose alkylators. Study aims were to define the
      toxicities and maximal-tolerated dose (MTD) of novobiocin and the
      pharmacokinetics of novobiocin and high-dose cyclophosphamide and thiotepa.
      PATIENTS AND METHODS: Thirty-eight women with responsive metastatic breast cancer
      received high-dose cyclophosphamide (3 to 6 g/m2 over 4 days), thiotepa (400 to
      800 mg/m2), and novobiocin (0.5 to 5.0 g/d x 7, orally) with autologous marrow
      support. Toxicity was monitored. The pharmacology of novobiocin,
      cyclophosphamide, and thiotepa was evaluated. RESULTS: There were no toxic
      deaths. The MTD of novobiocin was 4 g/d. All seven patients treated at 5 g/d
      developed grade III/IV mucositis and vomiting. The severity of mucositis
      correlated with the plasma levels of novobiocin. Other severe toxicities were not
      observed. Plasma novobiocin levels > or = 100 micrograms/mL, which are associated
      with reversal of drug resistance in animal models, were consistently seen at dose
      levels greater than 2 g. The dispositions of cyclophosphamide and thiotepa were
      not altered by novobiocin. CONCLUSION: Novobiocin may be given with high-dose
      alkylators in doses that produce plasma levels that augment the activity of these
      cytotoxics in experimental models. The pharmacology of high-dose cyclophosphamide
      and thiotepa is unaffected. Novobiocin 4 g/d orally for 7 days is recommended for
      future study.

PMID- 7738620
TI  - Natural history of node-negative breast cancer: a study of 826 patients with long
      term follow-up.
AB  - PURPOSE: We were interested in examining the long-term outcome of patients with
      node-negative breast cancer to address the following questions: (1) Is node
      negative breast cancer a disease that is curable by local modalities? (2) Are
      there predictors of disseminated disease in node-negative breast cancer? (3) Are
      there subgroups of tumors that have different times to recurrence? METHODS: From
      1927 to 1984, 826 women with node-negative breast cancer were treated at the
      University of Chicago. Patients underwent either a radical or extended radical
      mastectomy (83%) or a modified radical mastectomy (13%). RESULTS: Follow-up
      evaluation ranged from 9 to 523 months (43.6 years); the mean follow-up period of
      survivors is 162 months (13.5 years). On multivariate analysis, the strongest
      predictor of outcome and time to relapse was pathologic tumor size. Patients with
      tumors less than 2 cm had a 20-year disease-free survival (DFS) rate of 79% and a
      median time to recurrence of 48 months as compared with patients with tumors
      greater than 2 cm, who had a survival rate of 64% (P < .001) and a median time to
      recurrence of 37 months (P = .01). CONCLUSION: With extended follow-up
      evaluation, node-negative breast cancer is a curable disease. Size is the
      strongest predictor of dissemination and rate of relapse. These data suggest that
      given the natural history of node-negative breast cancer, analysis of clinical
      trials with short follow-up periods can be misleading, since it may identify
      those patients whose tumors have a greater virulence but not necessarily a
      greater likelihood to metastasize.

PMID- 7738621
TI  - Maintenance chemotherapy with daily oral etoposide following salvage therapy in
      patients with germ cell tumors.
AB  - PURPOSE: To evaluate the role of maintenance daily oral etoposide (VP-16)
      chemotherapy for germ cell patients who had a response to salvage therapy.
      PATIENTS AND METHODS: Thirty-seven patients were entered onto this trial, and 34
      were fully assessable. This was as heavily pretreated patient population, with a
      median of two prior salvage regimens. The salvage treatment that immediately
      preceded oral VP-16 consisted of autologous bone marrow transplantation in 14
      patients (41%), surgery in 10 (29%), and standard-dose salvage chemotherapy in 10
      (29%). Daily oral VP-16 was administered at a dose of 50 mg/m2 for 21 consecutive
      days every 4 weeks for three cycles. RESULTS: The major toxicity with daily oral
      VP-16 was leukopenia. Three patients had grade III and two grade IV leukopenia.
      Two of these patients had granulocytopenic fever. Other grade III toxicities
      included thrombocytopenia (n = 1) and mucositis (n = 2). Twenty-three patients
      started daily oral VP-16 while in complete remission (CR) following salvage
      therapy. Seventeen (74%) remain continuously disease-free, with a median follow
      up time of 36 months (range, 26 to 49) from initiation of daily oral VP-16.
      Eleven patients started daily oral VP-16 while in partial remission (PR)
      following salvage therapy. Three of these 11 patients converted to CR, but all
      three subsequently relapsed. CONCLUSION: Maintenance oral VP-16 was well
      tolerated in this heavily treated patient population. Results in this poor-risk
      population were encouraging.

PMID- 7738622
TI  - Failure of orally administered dipyridamole to enhance the antineoplastic
      activity of fluorouracil in combination with leucovorin in patients with advanced
      colorectal cancer: a prospective randomized trial.
AB  - PURPOSE: A randomized trial was performed to investigate the ability of the
      nucleoside transport inhibitor dipyridamole (DP) to enhance the antitumor
      activity of fluorouracil (5-FU)/leucovorin (folinic acid [FA]). PATIENTS AND
      METHODS: One hundred eighty-one untreated patients with advanced colorectal
      cancer were randomized to receive 5-FU 600 mg/m2 plus FA 300 mg/m2 on days 2 to 4
      with or without DP 75 mg orally three times daily on days 1 to 5. Cycles were
      repeated every 3 weeks. Only patients with documented tumor progression before
      therapy were eligible. 5-FU pharmacokinetics using high-performance liquid
      chromatography (HPLC) were assessed in 11 nonrandomized patients receiving paired
      cycles with or without DP. RESULTS: One hundred seventy-four patients were
      assessable for toxicity and response. There was no significant difference in
      toxicity, except DP-related headache in 24% of patients. An objective response
      rate of 15% (one complete response [CR] and 13 partial responses [PRs]) for 5
      FU/FA and 13% (two CRs and nine PRs) for 5-FU/FA/DP was observed. The dose
      intensity of 5-FU delivered was significantly higher (1.09- to 1.16-fold) for the
      DP-containing arm. Pharmacokinetic parameters of 5-FU did not differ
      significantly, except for a prolonged half-life (t1/2) induced by DP. The median
      time to progression (P = .8) and the median survival time (11.6 months for 5
      FU/FA v 9.3 months for 5-FU/FA/DP; P = .14, log-rank test) were not different
      between treatment arms. CONCLUSION: Orally administered DP did not improve the
      antineoplastic activity of 5-FU/FA in patients with advanced colorectal cancer
      when used at this dose and schedule. The observed increase in 5-FU dose-intensity
      for FU/FA/DP was not clinically relevant.

PMID- 7738623
TI  - Phase II study of daily oral etoposide plus ifosfamide plus cisplatin for
      previously treated recurrent small-cell lung cancer: a Hoosier Oncology Group
      Trial.
AB  - PURPOSE: The study was undertaken to determine the activity and toxicity of oral
      etoposide (VP-16), ifosfamide, and cisplatin combination chemotherapy for
      previously treated, recurrent small-cell lung cancer (SCLC). PATIENTS AND
      METHODS: In this phase II trial, 46 patients were enrolled to receive oral VP-16,
      37.5 mg/m2/d for 21 days, ifosfamide 1.2 g/m2/d for 4 days, and cisplatin 20
      mg/m2/d for 4 days, with courses repeated every 28 days. Response, survival, and
      toxicity data were then noted. RESULTS: Forty-two of 46 patients were assessable
      for response, survival, and toxicity. Thirty-six of 42 patients had received
      prior cisplatin plus VP-16. The first 22 patients received oral VP-16 for 21
      days, but the subsequent 20 patients received oral VP-16 for 14 days after an
      interim analysis showed marked myelosuppression. Twenty-three of 42 patients
      (55%) had an objective response, with six complete responses (CRs; 14%), and 17
      partial responses (PRs; 40%). The median progression-free survival time was 20
      weeks (range, 2 to 66) and the overall median survival duration was 29 weeks
      (range, 1 to 76). Myelosuppression was significant, with six treatment-related
      deaths, four as a result of sepsis. CONCLUSION: The combination of oral VP-16,
      ifosfamide, and cisplatin is an active regimen in the treatment of recurrent
      SCLC. However, hematologic toxicity was severe in this pretreated patient
      population.

PMID- 7738624
TI  - Long-term survival in small-cell lung cancer: posttreatment characteristics in
      patients surviving 5 to 18+ years--an analysis of 1,714 consecutive patients.
AB  - PURPOSE: To describe in patients with small-cell lung cancer (SCLC) the
      characteristics of those who survive for > or = 5 years, to identify long-term
      prognostic factors, to analyze survival data of 5-year survivors, and to study 10
      year survival in patients entered before 1981. PATIENTS AND METHODS: A total of
      1,714 unselected patients with SCLC were treated with combination chemotherapy in
      nine consecutive clinical trials from 1973 to 1991. All medical records were
      reviewed and follow-up data obtained to analyze and compare pretreatment and
      posttreatment characteristics. RESULTS: Sixty patients survived longer than 5
      years. Late relapses occurred in 15.0% of 5-year survivors and secondary
      malignancies in 20.0%. Twenty-six patients are still alive and disease-free 5 to
      18 years (median, 9.5 years) from initiation of treatment. Extensive-stage
      disease, performance status (PS) more than 2, liver and bone marrow metastases,
      and elevated lactate dehydrogenase (LDH) and alkaline phosphatase levels were all
      negative prognostic factors. The 5-year survival rate was 3.5% (limited-stage
      disease, 4.8%; extensive-stage disease, 2.3%), and the 10-year survival rate was
      1.8% (limited-stage disease, 2.5%; extensive-stage disease, 1.2%). CONCLUSION:
      Long-term survival can be achieved for both stages of SCLC, but without any
      change in survival rates over the last decade. Long-term survivors continuously
      seem to have considerable mortality due to late relapses and secondary
      malignancies, especially tobacco-related cancers and other tobacco-related
      diseases.

PMID- 7738625
TI  - Prognostic factors for survival in advanced non-small-cell lung cancer:
      univariate and multivariate analyses including recursive partitioning and
      amalgamation algorithms in 1,052 patients. The European Lung Cancer Working
      Party.
AB  - PURPOSE: This study attempted to determine the prognostic value for survival of
      various pretreatment characteristics in patients with nonresectable non-small
      cell lung cancer in the context of more than 10 years of experience of a European
      Cooperative Group. PATIENTS AND METHODS: We included in the analysis all eligible
      patients (N = 1,052) with advanced non-small-cell lung cancer registered onto one
      of seven trials conducted by the European Lung Cancer Working Party (ELCWP)
      during one decade. The patients were treated by chemotherapy regimens based on
      platinum derivatives. We prospectively collected 23 variables and analyzed them
      by univariate and multivariate methods. RESULTS: The global estimated median
      survival time was 29 weeks, with a 95% confidence interval of 27 to 30 weeks.
      After univariate analysis, we applied two multivariate statistical techniques. In
      a Cox regression model, the selected explanatory variables were disease extent,
      Karnofsky performance status, WBC and neutrophil counts, metastatic involvement
      of skin, serum calcium level, age, and sex. These results were confirmed by
      application of recursive partitioning and amalgamation algorithms (RECPAM), which
      led to classification of the patients into four homogeneous subgroups.
      CONCLUSION: We confirmed by our analysis the role of well-known independent
      prognostic factors for survival, but also identified the effect of the neutrophil
      count, rarely studied, with the use of two methods: a classical Cox regression
      model and a RECPAM analysis. The classification of patients into the four
      subgroups we obtained needs to be validated in other series.

PMID- 7738626
TI  - Effect of low-dose prophylactic dopamine on high-dose cisplatin-induced
      electrolyte wasting, ototoxicity, and epidermal growth factor excretion: a
      randomized, placebo-controlled, double-blind trial.
AB  - PURPOSE: To evaluate the protective effect of low-dose dopamine given as
      continuous infusion in patients who undergo chemotherapy with the nephrotoxin
      cisplatin. PATIENTS AND METHODS: Forty-two patients who received high-dose
      cisplatin-containing chemotherapy entered a prospective, randomized, double
      blind, placebo-controlled trial. Twenty-one patients received dopamine, and 21
      received placebo. Patients were to receive either infusional dopamine 2
      micrograms/kg/min over 48 hours or placebo. Cisplatin 125 mg/m2 was administered
      12 hours after initiating dopamine (group D) or placebo (group P). This schedule
      was repeated twice, 1 week apart. Measurements of serum creatinine, urinary
      electrolytes and creatinine, urinary excretion of epidermal growth factor (EGF),
      ototoxicity, parameters of hematopoietic recovery, and duration of
      hospitalization were analyzed. RESULTS: We observed an increase in serum
      creatinine level to a peak of 1.9 mg/dL (range, 0.8 to 7.8) in the dopamine
      group, in comparison to 1.4 mg/dL (range, 0.9 to 3.3) in the placebo group (P =
      .04). Urinary magnesium excretion increased and EGF excretion decreased in both
      groups. Urinary sodium, chloride, and potassium excretion were increased in both
      groups, but more so in the placebo group. Dopamine had no measurable effect on
      hearing loss, duration of hospitalization, or hematopoietic recovery. CONCLUSION:
      The use of prophylactic dopamine increased peak serum creatinine levels relative
      to placebo and failed to prevent cisplatin-induced renal toxicity or ototoxicity.
      Determination of whether dopamine could reverse chemotherapy-induced renal damage
      would require a randomized prospective trial.

PMID- 7738627
TI  - Pharmacokinetics of all-trans-retinoic acid administered on an intermittent
      schedule.
AB  - PURPOSE: Administration of all-trans-retinoic acid (ATRA) on a continuous daily
      schedule results in a rapid and sustained decrease in plasma drug concentrations.
      This pharmacokinetic study was performed to determine if administration of ATRA
      on an intermittent schedule could overcome the rapid decrease in plasma drug
      concentration and provide repetitive periods of higher plasma drug exposure.
      MATERIALS AND METHODS: ATRA was administered on repetitive cycles of 7
      consecutive days of drug followed by 7 days without drug. On the days of
      pharmacokinetic monitoring, following an overnight fast, a fixed single oral dose
      of 40 mg/m2 was administered and frequent plasma samples were obtained over 8
      hours. Patients had pharmacokinetic studies performed on the first and seventh
      days of the first week, and on the first day of the third and eleventh weeks.
      ATRA was measured in plasma with a reverse-phase high-performance liquid
      chromatography (HPLC) assay. RESULTS: Plasma exposure to ATRA as measured by the
      area under the plasma concentration-time curve (AUC) decreased significantly
      during the first week of drug administration, from a mean of 145 +/- 26
      mumol/L.min on day 1 to 18 +/- 4 mumol/L.min by day 7. Plasma ATRA concentrations
      at the start of weeks 3 and 11 of this every-other-week schedule were equivalent
      to those achieved on day 1 of treatment, with mean AUCs of 177 +/- 39 and 128 +/-
      30 mumol/L.min, respectively. CONCLUSION: An intermittent schedule of ATRA
      administration results in repetitive periods of exposure to concentrations of
      ATRA normally only observed on the first day of treatment. Phase II trials to
      evaluate the role of intermittent schedules of administration for ATRA are
      planned.

PMID- 7738628
TI  - Comparative clinical trial of granisetron and ondansetron in the prophylaxis of
      cisplatin-induced emesis. The Granisetron Study Group.
AB  - PURPOSE: To compare the efficacy and safety of granisetron and ondansetron,
      serotonin (5-HT3) receptor antagonists shown to be effective in the prevention of
      chemotherapy-induced emesis. PATIENTS AND METHODS: In a double-blind, randomized,
      stratified, parallel-group study, the efficacy and safety of granisetron and
      ondansetron were compared in 987 chemotherapy-naive patients who received
      cisplatin in doses > or = 60 mg/m2. Granisetron was administered as a single dose
      of 10 or 40 micrograms/kg before the start of chemotherapy. Ondansetron was
      administered in doses of 0.15 mg/kg before and 4 and 8 hours after the start of
      chemotherapy. The three treatment groups were well-matched with respect to
      demographic characteristics and the dose of cisplatin administered. RESULTS: For
      all evaluations, single doses of granisetron 10 or 40 micrograms/kg were as
      effective as three 0.15-mg/kg doses of ondansetron. Total control (no vomiting,
      no retching, no nausea, and no use of rescue) was attained by 38%, 41%, and 39%
      of all patients who received granisetron 10 microgram/kg, granisetron 40
      micrograms/kg, and ondansetron, respectively. No vomiting or retching and no use
      of rescue antiemetics were reported in 47%, 48%, and 51% of patients who received
      granisetron 10 micrograms/kg, granisetron 40 micrograms/kg, and ondansetron,
      respectively; no nausea and no use of rescue antiemetics were reported in 39%,
      42%, and 40% of patients, respectively. CONCLUSION: All three treatment regimens
      were well-tolerated. The results of this study indicate that a single dose of
      granisetron 10 or 40 micrograms/kg is as effective as three doses of ondansetron
      0.15 mg/kg in the prevention of nausea and vomiting induced by cisplatin
      chemotherapy.

PMID- 7738629
TI  - Test/retest study of the European Organization for Research and Treatment of
      Cancer Core Quality-of-Life Questionnaire.
AB  - PURPOSE: The European Organization for Research and Treatment of Cancer Core
      Quality of Life Questionnaire (EORTC QLQ-C30) is a well-validated instrument that
      assesses health-related quality of life (HRQOL) in cancer patients. It is used in
      cancer clinical trials in Europe, Canada, and the United States, and has
      demonstrated high reliability and validity in different groups of cancer
      patients. Despite thorough testing of reliability and validity, we have not
      identified any reports on its test/retest reliability; thus, a test/retest study
      was performed at the Norwegian Radium Hospital (NRH). MATERIALS AND METHODS:
      Cancer patients from the outpatient clinic who were off treatment for > or = 3
      months were eligible for the study. The EORTC QLQ-C30 was given to the patients
      when they presented for their visit. The second questionnaire was received by the
      patients 4 days later. Of 291 eligible patients, 270 (93%) agreed to participate
      and 190 (73%) completed both questionnaires. RESULTS: The test/retest reliability
      measured by Pearson's correlation coefficient was high for all functional scales,
      with a range from .82 for cognitive and role function to .91 for physical
      function. The r value for global HRQOL was .85. For the symptom scales-
      nausea/vomiting, fatigue, and pain--the coefficients were .63, .83, and .86,
      respectively. The single-item coefficients ranged from .72 for diarrhea to .84
      for financial impact. The Spearman rank correlation was in the same range for all
      dimensions. CONCLUSION: The EORTC QLQ-C30 seems to yield high test/retest
      reliability in patients with various cancer diagnoses whose condition is not
      expected to change during the time of measurement.

PMID- 7738630
TI  - Someone to live for: social well-being, parenthood status, and decision-making in
      oncology.
AB  - PURPOSE: Little is known about the influence of social factors on treatment
      preferences and desire for aggressive cancer therapy. The present study assessed
      subjective and objective social indicators in patient preferences for treatment.
      METHODS: Cancer patients (N = 296) with diverse diagnoses and stages read sets of
      hypothetical vignettes describing patients with early-stage and advanced disease.
      In the first set, patients made decisions about treatment acceptance given
      varying levels of either increasing cure or extending survival. In the second
      set, the point at which patients shifted preferences from mild to severe
      treatment to improve likelihood of 1-year survival (switch point) was the
      dependent measure. We assessed the impact of quality-of-life (QL) domains
      measured by the Functional Assessment of Cancer Therapy-General (FACT-G), having
      children, marital status, and living arrangements on treatment preferences and
      switch points. RESULTS: The Social Well-Being (SWB) subscale of the FACT-G
      predicted both treatment acceptance (P = .007) and switch point (P = .043) in the
      advanced-disease vignettes, with lower SWB associated with less aggressive
      preferences. Children living at home was likewise associated with more aggressive
      intent both in treatment preferences (P = .003, advanced-disease vignette) and
      switch point (P < .001 and P = .001 for early- and advanced-disease vignettes,
      respectively). Living with others predicted more aggressive intent in the
      advanced-disease vignette (P = .03). Marital status did not predict either
      treatment acceptance or switch point. CONCLUSION: Positive social well-being, as
      well as having children living at home, predicted patient willingness to accept
      aggressive treatment. Willingness to receive aggressive treatment may explain or
      mediate previously reported salutory effects of social support on cancer
      outcomes.

PMID- 7738631
TI  - Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung.
AB  - PURPOSE: Although standard treatment of stage I non-small-cell lung cancer
      (NSCLC) consists of surgical resection alone, approximately 50% of clinical stage
      I and 30% to 40% of pathologic stage I patients have disease recurrence and die
      following curative resection. A large number of traditional pathologic and newer
      molecular markers have been identified, which appear to have important prognostic
      significance in this population. This review attempts to summarize these data
      comprehensively. METHODS: Criteria for study selection were English-language
      reports, identified using Medline and Cancerline, through the fall of 1994.
      Abstracts from the American Society of Clinical Oncology (ASCO) and the
      International Association for the Study of Lung Cancer (IASLG) were also
      reviewed. RESULTS: Molecular markers are classified as molecular genetic markers,
      differentiation markers, proliferation markers, and markers of metastatic
      propensity. A number of these markers have been reported to be highly predictive
      of outcome in stage I NSCLC, and several reports conclude that a specific
      biomarker may be, aside from clinical stage, the most powerful determinant of
      prognosis in NSCLC. However, little has been done to clarify the relationships
      between these newer biologic markers, classic clinicopathologic variables, and
      clinical outcome. CONCLUSION: At present, a firm conclusion regarding which
      biomarkers are most important in predicting outcome is not possible, and a model
      that reliably integrates all independent prognostic variables cannot be
      developed. A prospective trial is mandatory to address this issue, and a study
      design is suggested that would facilitate the development of a prognostic index,
      while simultaneously asking a therapeutic question. The development of a
      prognostic index would facilitate future trials in which only high-risk stage I
      patients could be targeted for investigation of postresection adjuvant treatment
      strategies.

PMID- 7738632
TI  - Autologous blood transfusions and prognosis in colorectal cancer surgery.

PMID- 7738633
TI  - Intensified concomitant chemoradiotherapy for poor-prognosis head and neck
      cancer.

PMID- 7738634
TI  - Treatment of elderly patients with antineoplastic chemotherapy.

PMID- 7738635
TI  - Application of the Cotswolds Criteria for the assessment of disease response in
      patients treated for Hodgkin's disease.

PMID- 7738636
TI  - Complete remission in T-cell prolymphocytic leukemia with 2-chlorodeoxyadenosine.

PMID- 7738637
TI  - DOE's plan for A-bomb studies incites anger in Japan.

PMID- 7738638
TI  - A time for renewal.

PMID- 7738639
TI  - How to make PET cost effective.

PMID- 7738640
TI  - Technetium-99m-methylene diphosphonate scintimammography to image primary breast
      cancer.
AB  - Technetium-99m-methylene diphosphonate (MDP) uptake within breast lesions was
      investigated during routine presurgical bone scintigraphy in a cohort of women at
      high risk for cancer who were candidates for surgery or excisional biopsy. The
      aim was twofold: (a) to demonstrate positive 99mTc-MDP uptake in primary breast
      cancer and (b) to differentiate malignant from benign lesions. METHODS: Anterior
      and oblique lateral views of the breasts were acquired 0-4 min, 10-20 min and 2
      hr after intravenous injection of 740 MBq of 99mTc-MDP in 200 women with elevated
      suspicion or proven diagnosis of breast cancer (Group 1) and in 80 women with
      other solid tumor types (Group 2). RESULTS: Physical examination and mammography
      revealed breast abnormalities in all Group 1 subjects. The mammographic findings
      were definitely positive for carcinoma in 120 patients, highly suspicious in 27
      and indeterminate in 53. Breast cancer was later histologically diagnosed in 172
      women (86%) and benign disease found in 28 women (14%). Of these patients, 158
      (92%) showed focal uptake of 99mTc-MDP in the images collected 10-20 min after
      injection. This was found to be the best timing for imaging, with tumor-to
      background ratios as high as 4.3 (mean +/- s.d. = 3.8 +/- 0.4). Two hr after
      injection, only 61 of the 158 (38%) malignant lesions were clearly detectable.
      CONCLUSION: Technetium-99m-MDP is concentrated by primary breast carcinoma 10-20
      min after injection, enabling successful external gamma imaging.
      Scintimammography with 99mTc-MDP is an accurate test that differentiates
      malignant from benign breast lesions, particularly in patients with indeterminate
      mammograms.

PMID- 7738641
TI  - Pharmacokinetics, dosimetry and toxicity of holmium-166-DOTMP for bone marrow
      ablation in multiple myeloma.
AB  - In this Phase I clinical trial, six multiple myeloma patients who had not
      responded to conventional therapy and were scheduled for bone marrow
      transplantation received a bone-seeking radiopharmaceutical for bone marrow
      ablation. The pharmacokinetics, dosimetry, and toxicity of this
      radiopharmaceutical were studied. METHODS: Patients received from 519 mCi to 2.1
      Ci (19.2 GBq to 77.7 GBq) of holmium-166 (166Ho) complexed with a bone-seeking
      agent, DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic
      acid). The reproducibility of pharmacokinetics from multiple injections of 166Ho
      DOTMP administered to these myeloma patients was demonstrated from blood (r2 =
      0.926) and whole-body retention (r2 = 0.983), which allowed therapeutic
      parameters to be determined from a diagnostic study. RESULTS: Over 50% of the
      166Ho-DOTMP injected dose was excreted within 2-3 hr postinjection, increasing to
      75%-85% over a 24-hr period. Rapid blood clearance minimized radiation dose to
      nontarget tissue: less than 10% of the injected activity was retained in the
      blood pool at 1 hr postinjection, and less than 2% remained after 5 hr. The total
      radiation absorbed dose delivered to the bone marrow for the six patients ranged
      from 7.9 Gy to 41.4 Gy. CONCLUSION: All patients demonstrated severe bone marrow
      toxicity with a white blood cell (WBC) count < 1,000 cells/microliters, two
      patients exhibited marrow ablation (WBC count < 100 cells/microliters), and no
      other toxicity > or = grade 2 was observed in any of the patients.

PMID- 7738642
TI  - Preoperative scintigraphy and operative probe scintimetry of colorectal carcinoma
      using technetium-99m-88BV59.
AB  - We report a pilot study of radioimmunoscintigraphy (RIS) and operative gamma
      probe scintimetry (OPS) using a 99mTc-labeled anti-cytokeratin human monoclonal
      antibody (MAb) (99mTc-88BV59) in patients with newly diagnosed, recurrent or
      metastatic colorectal cancer. METHODS: Twelve presurgical patients with biopsy-
      or contrast radiographic-proven colorectal cancer or recurrent colorectal
      carcinoma were studied. After chest roentgenography and abdominopelvic CT, 99mTc
      88BV59 was administered intravenously, planar and SPECT external imaging was
      performed 3 to 6 hr after injection and planar imaging was performed 18 to 24 hr
      after injection. Surgery was performed immediately after late planar imaging. OPS
      of a standardized list of sites to document background radiation activity and of
      tumor sites, resection margins and tumor beds was performed. RESULTS: The
      patients had 23 histologically proven tumor sites. Overall sensitivity for CT,
      planar RIS, SPECT, surgery and OPS was 43%, 61%, 78%, 96% and 91%, respectively.
      SPECT was superior to CT for imaging extrahepatic abdominal and pelvic disease.
      OPS detected all liver and extrahepatic abdominal tumor sites and correctly
      predicted histological tumor-free margins and tumor beds in all cases. OPS did
      not identify tumor deposits that the surgeon could neither see nor feel. No
      patient demonstrated human anti-human immune responsiveness 1 and 3 mo after
      99mTc-88BV59 infusion. CONCLUSION: Technetium-99m-88BV59 is a safe, effective
      radioimmunoconjugate for colorectal cancer imaging, with superior sensitivity as
      compared to CT.

PMID- 7738643
TI  - Anti-chelate antibodies after intraperitoneal yttrium-90-labeled monoclonal
      antibody immunoconjugates for ovarian cancer therapy.
AB  - The development of stable chelating agents for metal isotopes (e.g., 90Y) such as
      CITC-DTPA, a benzyl-analog of DTPA, allowed us to evaluate the efficacy of 90Y
      labeled HMFG1 MAb administered intraperitoneally in patients with ovarian cancer.
      Our previous studies of 90Y-HMFG1 antibody, however, showed that all patients
      developed anti-chelate antibody responses (to the macrocycle benzyl-DOTA),
      resulting in clinical side effects in a significant percentage of this group.
      METHODS: We evaluated the immunogenicity of CITC-DTPA (administered to 12
      patients as 90Y-HMFG1-CITC-DTPA after coupling it to HSA using solid-phase ELISA.
      RESULTS: Eleven of 12 evaluable patients developed anti-CITC-DTPA antibodies.
      Five patients (approximately 40%) developed hypersensitivity syndrome, most
      likely due to a type III immune reaction (serum sickness). Most patients had a
      low titer of pre-existing anti-chelate response which correlated positively with
      post-therapy response levels (p = 0.001). IgM anti-CITC-DTPA antibodies developed
      2 wk while IgG antibodies developed 3 wk after treatment. Western blot analysis
      of post-therapy sera revealed a reaction with HSA-CITC-DTPA (60 kDa band) and no
      reaction with HSA or HSA-DTPA, whereas pre-therapy sera of the same patients were
      negative to all antigens. CONCLUSION: CITC-DTPA is immunogenic in patients after
      intraperitoneal administration of 90Y-CITC-DTPA labeled MAbs. Self-limiting
      clinical side effects consistent with a serum sickness-like immune reaction were
      observed in 5 of 12 patients.

PMID- 7738644
TI  - Pharmacokinetics and normal organ dosimetry following intraperitoneal rhenium-186
      labeled monoclonal antibody.
AB  - Pharmacokinetics, biodistribution and radiation dose estimates following
      intraperitoneal administration of a 186Re-labeled murine antibody, NR-LU-10, were
      assessed in 27 patients with advanced ovarian cancer. METHODS: Quantitative gamma
      camera imaging and gamma counting of serum and intraperitoneal fluid
      radioactivity were used to obtain data for dosimetry estimation. The MIRD
      intraperitoneal model was used to estimate dose to normal organs from
      radioactivity within the peritoneal cavity. The absorbed dose to normal
      peritoneum was estimated in two ways: from the gamma camera activity and
      peritoneal fluid samples. RESULTS: Serum activity peaked at 44 hr and depended on
      the concentration of radioactivity in the peritoneal fluid. Mean cumulative
      urinary excretion of 186Re was 50% by 140 hr. Estimates of radiation absorbed
      dose to normal organs in rad/mCi administered (mean +/- s.d.) were whole body 0.7
      +/- 0.3; marrow 0.4 +/- 0.1; liver 1.9 +/- 0.9; lungs 1.3 +/- 0.7; kidneys 0.2 +/
      0.2; intestine 0.2 +/- 0.2. Peritoneal surface dose estimates varied depending
      on the volume of fluid infused and the method of dose determination. Using gamma
      camera data, the peritoneal dose ranged from 7 to 36 rad/mCi. Using peritoneal
      fluid sample data, the dose ranged from 2 to 25 rad/mCi. Significant
      myelosuppression was observed at marrow doses above 100 rad. CONCLUSION:
      Noninvasive methods of dose estimation for intraperitoneal administration of
      radioimmunoconjugates provide reasonable estimates when compared with previously
      described methods.

PMID- 7738645
TI  - Thallium-201 SPECT and technetium-99m-phytate subtraction liver imaging in the
      evaluation of pancreatic cancers.
AB  - We preliminarily evaluated the usefulness of 201Tl SPECT in the investigation of
      pancreatic cancers. METHODS: The subjects included 32 patients with malignant
      tumors, 16 with benign disorders and 10 controls. SPECT was performed 10 min
      after the injection of 148-222 MBq of 201Tl; subjects had fasted to minimize
      intestinal activity. In addition, subtracted SPECT using 99mTc-phytate to
      separate the boundary of abnormal uptake from liver activity was carried out in
      14 patients. RESULTS: Thallium-201 did not accumulate in the pancreatic bed of
      the controls. In contrast, 29 of the 32 patients with malignant tumors showed
      positive phytate uptake with a sensitivity of 90.6% in the detection of
      malignancy. Of the 16 benign disorders, only four patients showed abnormal
      uptake; however, the mean value of the lesion-to-hepatic ratio (0.43 +/- 0.06;
      range, 0.35-0.51), as an index of the degree of uptake, was lower than that in
      positive malignant tumors (0.72 +/- 0.16; range, 0.53-1.28). Thallium-201
      activity per milligram of resected cancer tissue in two patients was 2-3 times
      greater than in normal tissue. Follow-up 201Tl SPECT in the five treated patients
      demonstrated similar alterations between 201Tl uptake and tumor markers.
      CONCLUSION: Our results suggest that 201Tl SPECT may have clinical potential in
      the investigation of pancreatic cancers.

PMID- 7738646
TI  - Scintigraphic evaluation of pancreatic transplants using technetium-99m
      sestamibi.
AB  - The purpose of this study was to evaluate the feasibility of using 99mTc
      sestamibi in the assessment of pancreatic transplant. METHODS: Ten transplant
      recipients with a history of insulin-dependent diabetes mellitus were studied.
      Fourteen 99mTc-sestamibi studies were performed. Each patient was injected
      intravenously with 10 mCi of 99mTc-sestamibi. Two-second frames were obtained for
      1 min, followed by serial dynamic and static images every 5 min for 30 min.
      Technetium-99m sestamibi studies, read by two nuclear medicine physicians, were
      correlated with clinicopathologic findings and compared to the ten 201Tl studies
      obtained in seven of these patients. RESULTS: On 99mTc-sestamibi images, normally
      functioning grafts showed adequate perfusion on the angiogram and good uptake
      followed by clearance on static images. Time-activity curves showed an initial
      upslope followed by a downslope after the initial uptake peak. The quality of
      99mTc-sestamibi images was superior to those of 201Tl in five, similar in four
      and marginally inferior in one paired study. Technetium-99m-sestamibi was used
      for both flow and static images, whereas a 99mTc radiotracer angiogram was needed
      to accompany the 201Tl study. CONCLUSION: Our preliminary experience indicates
      that 99mTc-sestamibi helps evaluate pancreatic transplants and provides high
      count statistics, which result in better image quality and diagnostic detail.
      Extensive quantitative studies are being performed to further evaluate this
      agent's role in the clinical management of pancreatic transplant patients.

PMID- 7738647
TI  - Identification of Hurthle cell tumor by single-injection, double-phase
      scintigraphy with technetium-99m-sestamibi.
AB  - Early and late (double-phase) scintigraphy with 99mTc-MIBI was used in a
      comparative study of the scintigraphic aspects of Hurthle cell tumors and other
      thyroid tumors. METHODS: Single-injection, dual-phase (15-30 min and 3-4 hr)
      thyroid scintigraphy with 99mTc-sestamibi (MIBI) was performed on 41 patients who
      displayed a cold nodule on previous 99mTc scintigraphy. Visual scoring of nodular
      uptake was done to compare thyroidal and background tracer uptake. In addition,
      the nodular-to-thyroid (N/T) uptake ratio in the early and late images and the
      washout rate from the nodule (WON) and thyroidal tissue (WOT) were measured.
      Cytologic results were obtained for all patients; histopathologic results were
      obtained for the 20 patients who had surgery. RESULTS: In eight patients (Group
      A), the nodule displayed intense and persistent uptake of MIBI (N/T = 1.77 +/-
      0.46 and 3.20 +/- 1.37; WON = 17.2% +/- 6.3%; WOT = 24.6% +/- 7.5%);
      histopathology revealed Hurthle cell tumors (two carcinomas and three adenomas)
      in five surgical patients. In 15 patients (Group B), the nodule displayed intense
      uptake in the early image with fading activity in the late image (N/T = 1.45 +/-
      0.54 and 0.84 +/- 0.30; WON = 30.0% +/- 7.3%; WOT = 24.5% +/- 6.8%);
      histopathology revealed a colloid nodule (n = 1), papillary carcinoma (n = 4) and
      follicular carcinoma (n = 5) in 10 surgical patients. In the remaining 18
      patients (Group C), the nodule was cold and late images were not acquired.
      Histopathology revealed colloid nodules (n = 2) and follicular adenoma (n = 3) in
      five surgical patients. CONCLUSION: Single-injection, dual-phase MIBI
      scintigraphy of the thyroid can identify Hurthle cell tumors because these tumors
      have intense, persistent tracer uptake in contrast to other thyroid tumors.

PMID- 7738648
TI  - Effect of radioiodine therapy on pulmonary alveolar-capillary membrane integrity.
AB  - The effects of large doses of radioiodine on the pulmonary alveolar-capillary
      membrane using 99mTc-DTPA clearance as an index of pulmonary damage in subjects
      with pulmonary metastases of differentiated thyroid carcinoma were studied.
      METHODS: Technetium-99m-DTPA radioaerosols were generated by a dry aerosol
      generator. Data were acquired and analyzed for clearance half-time from the lungs
      with a scintillation camera. The study was carried out on 35 thyroid cancer
      patients with pulmonary metastases and on 32 patients without metastases; the
      results were compared to those of a control group comprising 52 subjects. The
      radiation dose delivered to the lungs from the therapeutic dose was calculated
      using MIRD methodology. RESULTS: Cumulative radioiodine doses varied from 5.9 to
      44.2 GBq (158-1194 mCi). The half-time clearance of 99mTc-DTPA was comparable in
      both patient groups and was not related to the total administered radioiodine
      dosage or to the radiation dose delivered to the lungs. No changes were observed
      for periods up to 5 yr after receiving the last radioiodine dosage. Seven
      patients followed at regular intervals from 6 mo to 2 yr did not show abnormal
      99mTc-DTPA clearance values. One patient did show low 99mTc-DTPA clearance half
      time values, which were symptomatic radiation pneumonitis. She had received a
      total dose of 34 GBq (922 mCi) over a 4-yr period. CONCLUSION: The incidence of
      pulmonary damage resulting from radioiodine therapy for lung metastases of
      differentiated thyroid cancer is negligible, as evidenced by the normal pulmonary
      clearance half-time of 99mTc-DTPA aerosols.

PMID- 7738649
TI  - Detecting recurrent or residual lung cancer with FDG-PET.
AB  - We investigated the diagnostic accuracy of FDG-PET in the detection of recurrent
      lung cancer. METHODS: Thirty-nine lesions in 38 patients with clinically
      suspected recurrent or residual lung cancer were studied with PET. All PET images
      were visually interpreted in conjunction with thoracic CT or MRI.
      Semiquantitative analysis using standardized uptake values (SUVs) was also
      performed in 25 lesions. FDG-PET diagnoses were correlated with pathological
      diagnoses and clinical outcome. RESULTS: The sensitivity and specificity of FDG
      PET for detecting recurrent tumors were 100% (26/26) and 61.5% (8/13),
      respectively. The difference in mean SUV between recurrent tumors and
      noncancerous lesions was statistically significant [11.2 +/- 5.7 (n = 16) vs. 3.5
      +/- 1.8 (n = 9), p < 0.0001]. False-positive results showed relatively lower SUVs
      than true-positives and also demonstrated increased uptake in a curvilinear
      rather than nodular shape. CONCLUSION: FDG-PET is useful for detecting recurrent
      lung cancer after treatment. False-positive diagnoses might be reduced by
      analysis of uptake shape and serial changes in SUV, but further study is needed.

PMID- 7738650
TI  - Quantitative PET imaging of bone marrow glucose metabolic response to
      hematopoietic cytokines.
AB  - To evaluate the effects of hematopoietic cytokines on bone marrow glucose
      metabolism noninvasively, we studied serial quantitative FDG-PET images in 18
      patients with metastatic melanoma and normal bone marrow who were undergoing
      granulocyte-macrophage colony-stimulating factor (GMCSF) or macrophage colony
      stimulating factor (MCSF) administration as an adjunct to chemotherapy. METHODS:
      All patients received 14 days of cytokine therapy in three groups: four patients
      were treated with GMCSF (5 micrograms/kg/d SQ), eight patients were treated with
      GMCSF (5 micrograms/kg/d SQ) and monoclonal antibody (MAbR24) and six patients
      were treated with MCSF (80 micrograms/kg/d IVCI) and MAbR24. Dynamic FDG-PET
      imaging was performed over the lower thoracic or upper lumbar spine at four time
      points in each patient. RESULTS: Baseline glucose metabolic rates in the bone
      marrow of these three groups of patients were similar (5.2 +/- 0.7, 4.4 +/- 0.8
      and 4.8 +/- 1.2 micrograms/min/g as mean value and standard deviations,
      respectively). In both GMCSF and GMCSF + R24 groups, rapid increases in bone
      marrow glucose metabolic rates were observed during therapy. After GMCSF was
      stopped, bone marrow glucose metabolic rates rapidly decreased in both groups.
      The glucose metabolic response in these two groups was not significantly
      different by pooled t-statistics (p = 0.105). In the MCSF+R24 group, the increase
      of glucose metabolic rate on Days 3 and 10 was 35% and 31% above baseline on the
      average, but was not significant. CONCLUSION: The results support the use of
      parametric FDG-PET imaging for noninvasive quantitation of bone marrow glucose
      metabolic changes to hematopoietic cytokines in vivo.

PMID- 7738651
TI  - Avid uptake of technetium-99m-HMPAO by an intracranial plasmacytoma during
      carotid balloon test occlusion.
AB  - A 56-yr-old woman was evaluated for removal of a tumor at the base of the skull.
      A test to determine the risk of carotid artery sacrifice was performed prior to
      surgery using carotid balloon occlusion of the left internal carotid artery and
      99mTc-HMPAO perfusion scintigraphy during the occlusion. An unusual intense focus
      of increased uptake was seen at the site of the primary tumor in the left
      cavernous sinus. The tumor, found to be plasmacytoma at surgery, demonstrated
      only mild washout from 30 min to 2 hr after administration of 99mTc-HMPAO, with a
      tumor-to-cerebellum ratio of 1.6 and 1.5, respectively, and a tumor-to
      contralateral cranial ratio of 2.5 and 2.4, respectively. Intracranial
      plasmacytoma shows good response to radiation therapy, and the differentiation of
      this tumor from other neoplasms is pertinent to the mode of treatment and
      surgical approach. Technetium-99m-HMPAO SPECT imaging may be a useful tool in
      distinguishing these tumors from other neoplasms at the base of the skull.

PMID- 7738652
TI  - Increased technetium-99m-HMPAO uptake in grade II astrocytoma.
AB  - Most brain tumors show decreased uptake of blood flow tracers in brain SPECT
      imaging and in some cases meningiomas show increased uptake, mainly associated
      with high regional blood flow values. A reason for regionally increased tracer
      uptake is partial epilepsy when a tracer is injected during the ictal phase. We
      present a case of a histologically proven Grade II astrocytoma in the mesial part
      of the left temporal lobe that caused complex partial seizures. After tracer
      injection during a phase without signs of clinical seizure, markedly increased
      uptake of 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) occurred, although
      the tumor was partially calcified.

PMID- 7738653
TI  - Radiolabeled somatostatin analog scintigraphy in differentiated thyroid
      carcinoma.
AB  - After intravenous administration of a radiolabeled somatostatin analog
      (octreotide), an image of the thyroid gland is frequently observed; few data are
      available, however, on somatostatin receptors in epithelial thyroid cells
      assessed in vitro and on images of differentiated thyroid carcinoma (DTC) with
      pentetreotide scintigraphy. METHODS: In four patients with metastatic thyroid
      carcinoma, whole-body scintigraphy was performed 4 to 48 hr after injection of
      110 MBq of 111In-pentetreotide. The results were compared to data obtained with
      other imaging modalities, including scintigraphy performed after administration
      of a therapeutic dose of 131I. RESULTS: There were positive foci in distant
      metastases on 111In-pentetreotide scintigraphy. Pentetreotide scintigraphy was
      positive in two patients with an "insular" form of DTC, one of whom had a
      positive (faintly) 131I scan. Of the other two patients with papillary DTC
      without radioiodine uptake, only one exhibited a certain degree of pentetreotide
      scintigraphy positivity in distant metastases. CONCLUSION: These results show
      promise for exploration of insular thyroid carcinoma and suggest that these
      carcinomas may possess functional differentiation features, including
      somatostatin receptors.

PMID- 7738654
TI  - Technetium-99m MIBI uptake in recurrent parathyroid carcinoma and brown tumors.
AB  - Demonstrable parathyroid adenoma in delayed (3-hr) 99mTc-MIBI neck imaging and
      localization of 201Tl-chloride in brown tumors mimicking skeletal metastases have
      been reported. Technetium-99m-MIBI scintigraphy is currently the imaging modality
      of choice for localizing parathyroid tumors in patients with recurrent
      hyperparathyroidism. This report is a good example of the use of 99mTc-MIBI in
      the diagnostic work-up of a patient with recurrent hyperparathyroidism, which
      turned out to be due to parathyroid carcinoma rather than the initial
      histopathologic diagnosis of parathyroid adenoma. Additionally, the patient's
      total body 99mTc-MIBI and 99mTc-MDP bone images showed multiple focal lesions in
      the bone-mimicking metastases.

PMID- 7738655
TI  - Gallium and thallium scintigraphy in pediatric peripheral primitive
      neuroectodermal tumor (Askin tumor) of the chest wall.
AB  - A 3.5-yr-old child presented with a large thoracic mass which showed avid
      accumulation of 67Ga and 201Tl was studied. Histology showed a peripheral
      neuroectodermal tumor of the chest wall typical of the malignancy described as
      the Askin tumor. The 201Tl studies were a more accurate method of following tumor
      response to therapy than 67Ga scintigraphy.

PMID- 7738656
TI  - Diffuse renal retention on bone scintigraphy in localized clear-cell renal
      epithelial neoplasm.
AB  - Bone scintigraphy performed to assess the significance of an incidental finding
      of a small sclerotic rib lesion on a chest radiograph of a patient with no known
      malignancy demonstrated no evidence of metastatic disease, but there was moderate
      diffuse parenchymal retention in the left kidney. Renal ultrasound revealed an
      ovoid, slightly hyperechoic mass in the inferior pole of the left kidney, and
      subsequent contrast CT demonstrated a well-circumscribed hypervascular mass in
      that location. At nephrectomy, a localized 1.5-cm diameter clear-cell epithelial
      neoplasm, not definitely malignant, was found. No other abnormalities were noted
      in the remainder of the left kidney or in the surrounding soft tissues. No
      calcifications or other parenchymal changes in the kidney were identified to
      explain the retention of the bone agent, which was possibly related to the
      hyperemia associated with the neoplasm and undefined parenchymal factors.

PMID- 7738657
TI  - Metastatic calcification of multiple visceral organs in non-Hodgkin's lymphoma.
AB  - A patient with non-Hodgkin's lymphoma who developed acute hypercalcemia following
      chemotherapy was evaluated for skeletal metastases with a whole-body bone scan.
      Although metastatic disease is an unlikely cause of hypercalcemia, considering
      the acutely rising serum calcium, the bone scan is useful in excluding multiple
      metastases as a cause. In addition, the study demonstrated metastatic
      calcification in multiple organs, including the pancreas which is uncommon, and
      the liver and spleen, which is rare.

PMID- 7738658
TI  - Bone scintigraphy in growth hormone-secreting pulmonary cancer and hypertrophic
      osteoarthropathy.
AB  - Hypertrophic osteoarthropathy was detected in a 55-yr-old man with pulmonary
      squamous-cell cancer by bone scintigraphy using 99mTc-hydroxy methylene
      diphosphonate (HMDP). Intense symmetrical uptake was demonstrated in the distal
      portions of the long bones as was the parallel tract sign, accompanied by
      markedly elevated serum growth hormone levels. After chemoradiotherapy for
      pulmonary cancer, the arthralgia disappeared and scintigraphic findings and serum
      growth hormone levels improved, suggesting that ectopic production of growth
      hormone in the pulmonary tumor had been associated with hypertrophic
      osteoarthropathy. These findings indicate that bone scintigraphy is useful for
      detecting hypertrophic osteoarthropathy, and assessing alterations in
      hypertrophic osteoarthropathy activity post-treatment.

PMID- 7738659
TI  - Technetium-99m-sestamibi/thallium-201 mismatch of thyroid and parathyroid adenoma
      in chronic renal failure.
AB  - We report on a patient who had chronic renal failure and relapse of secondary
      hyperparathyroidism after earlier extirpation of three glands. Whereas 201Tl
      chloride uptake was absent in the thyroid and an ectopic parathyroid adenoma
      during routine subtraction 201Tl-99mTc scintigraphy, both glands could be
      visualized with 99mTc-sestamibi and [123I]sodium.

PMID- 7738660
TI  - Pharmacokinetics of chimeric L6 conjugated to indium-111- and yttrium-90-DOTA
      peptide in tumor-bearing mice.
AB  - A bifunctional chelating agent, DOTA-Gly3-L-(p-isothiocyanato)-phenylalanine
      amide (DOTA-peptide-NCS), was studied in nude mice bearing human breast cancer
      xenographs (HBT 3477) to determine its potential for radioimmunoconjugate
      therapy. METHODS: Indium-111 and yttrium-90 were attached to an anti
      adenocarcinoma chimeric L6 (ChL6) monoclonal antibody (MAb) after pre-chelation
      to the DOTA-peptide-NCS and the desired neutral radiochelates were obtained by
      purification. The unique characteristic of the DOTA-peptide-NCS to form neutral
      complexes with trivalent metals was utilized to separate the resulting 111In and
      90Y radiochelates from excess chelating agent and other anionic by-products
      resulting from metal impurities. The purified radiochelates were then conjugated
      to ChL6. The pharmacokinetics of 111In- and 90Y-DOTA-peptide-ChL6 were obtained
      for 5 days after injection in nude mice bearing HBT 3477 xenographs. The results
      were compared with the pharmacokinetics of 125I-ChL6 obtained in the same mouse
      model. RESULTS: The whole-body clearance of 125I-ChL6, 90Y- and 111In-DOTA
      peptide-ChL6 was monoexponential with biologic half-times of 92, 104 and 160 hr,
      respectively. Blood clearances of the three radiopharmaceuticals were biphasic.
      The radiometal immunoconjugates had greater tumor uptake and slower clearances.
      CONCLUSION: Indium-111- and 90Y-DOTA-peptide-ChL6 can be produced at high
      specific activity with fewer than one chelate per MAb by using a pre-labeling
      method that permits radiochelate purification by charge selection. Studies in
      mouse xenografts indicate that tumor uptake is enhanced and a favorable
      therapeutic index is achieved using these agents.

PMID- 7738661
TI  - Improved targeting of radiolabeled streptavidin in tumors pretargeted with
      biotinylated monoclonal antibodies through an avidin chase.
AB  - Radiolabeled streptavidin can be accumulated in tumors pretargeted with
      biotinylated anti-tumor antibodies. However, circulating biotinylated antibody
      and endogenous biotin may interfere with the tumor targeting of streptavidin. To
      reduce biotinylated antibody concentration in the blood, we injected avidin
      before streptavidin administration. The effects of avidin administration on the
      biodistribution and tumor targeting of radiolabeled streptavidin were examined.
      METHODS: Biotinylated anti-human colon cancer monoclonal antibody (MAb) MLS128
      was injected intravenously into nude mice bearing human colon cancer xenografts
      for pretargeting. After intraperitoneal injection of avidin, radioiodinated
      streptavidin was administered and its biodistribution and tumor accumulation was
      investigated. RESULTS: Radioiodinated streptavidin specifically localized in the
      tumor pretargeted with biotinylated antibody. Avidin preadministration
      accelerated the tumor uptake and blood clearance of radioiodinated streptavidin.
      The tumor-to-blood radioactivity ratio at 6 and 24 hr after radiolabeled
      streptavidin injection were 1.23 +/- 0.29 and 3.04 +/- 0.86, respectively, in
      mice with avidin chase (mean +/- s.d., n = 7), and 0.82 +/- 0.17 and 2.29 +/-
      0.29, respectively, in those without chase (mean +/- s.d., n = 7). CONCLUSION:
      Localization of radiolabeled streptavidin in tumors pretargeted with biotinylated
      MAb could be improved by avidin chase. This approach may be useful for tumor
      radioimmunoimaging and radioimmunotherapy.

PMID- 7738662
TI  - Direct technetium-99m labeling of three anticancer monoclonal antibodies:
      stability, pharmacokinetics and imaging.
AB  - Monoclonal antibodies (MAbs) directly labeled with 99mTc have been used in a
      number of clinical immunoscintigraphic investigations. Three anti-cancer MAbs
      were radiolabeled with 99mTc using a reduction-mediated technique. The stability,
      biodistribution and in vivo pharmacokinetics were assessed and compared with the
      same antibodies labeled with 125I. METHODS: Immunoreactivity data were obtained
      by ELISA and RIA. Homogeneity and stability of radiolabeled antibodies (in vitro
      and in vivo) were measured by size-exclusion, fast protein liquid chromatography
      and SDS-PAGE. Pre-clinical, in vivo investigations utilized the nude mouse/HEp2
      xenograft model, and clinical imaging and pharmacokinetic data were obtained from
      patients with confirmed or suspected lesions. RESULTS: Both 99mTc- and 125I
      labeled antibodies were shown to be homogeneous and stable, although 99mTc
      labeled antibody fragments were detected by SDS-PAGE. Pharmacokinetic studies in
      patients revealed a significant difference in the clearance rates between 99mTc-
      and 125I-labeled antibodies, with those labeled with 99mTc having a shorter
      biological half-life, indicating that the 99mTc-labeled antibodies may be less
      stable than the iodinated ones. Nevertheless, specific tumor localization was
      successfully demonstrated in nude mice bearing a human tumor xenograft using 125I
      and 99mTc-labeled H17E2 antibody. Furthermore, in the clinic, using 99mTc
      labeled HMFG1 and 1A3, successful imaging was achieved in 12 out of 19 patients
      with lesions for which these antibodies were specific. CONCLUSION: Anticancer
      MAbs radiolabelled using this reduction-mediated technique are suitable agents
      for clinical, immunoscintigraphic investigations.

PMID- 7738663
TI  - Preparation, biodistribution and dosimetry of copper-64-labeled anti-colorectal
      carcinoma monoclonal antibody fragments 1A3-F(ab')2.
AB  - Antibody fragments labeled with a radiometal using bifunctional chelates
      generally undergo renal clearance followed by trapping of the metabolites,
      leading to high radiation doses to the kidneys. Copper-64-labeled BAT-2IT-1A3
      F(ab')2 was recently reported to accumulate in colorectal tumors in an animal
      model, however, kidney uptake was also high. In this study, the preparation of
      64Cu-BAT-2IT-1A3-F(ab')2 was optimized to reduce the renal uptake. METHODS: The
      bifunctional chelate 6-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane-N,N
      ',N",N'"-tetraacetic acid (BAT) was conjugated to 1A3-F(ab')2 using the linking
      agent 2-iminothiolane (2IT). The conjugation reaction produced 20% of a lower
      molecular weight (molecular wieght) impurity found to be TETA-1A3-Fab'. The
      conjugation procedure was optimized to include FPLC purification of the BAT-2IT
      1A3-F(ab')2 from TETA-1A3-Fab' after conjugation prior to labeling with 64Cu. The
      biodistribution of 64Cu-labeled FPLC-purified and unpurified conjugates was
      determined in normal Sprague-Dawley rats and tumor bearing Golden Syrian
      hamsters. Human absorbed doses were calculated from rat biodistribution data and
      PET imaging of a baboon. RESULTS: Upon FPLC purification of the BAT-2IT-1A3
      F(ab')2, the immunoreactivity of 64Cu-labeled 1A3-F(ab')2 was significantly
      improved over that of non-FPLC-purified 64Cu-BAT-2IT-1A3-F(ab')2, and the kidney
      uptake was decreased in normal rats. The biodistribution in hamsters showed some
      improvement in both tumor uptake and kidney clearance with FPLC-purified 64Cu-BAT
      2IT-1A3-F(ab')2. CONCLUSION: The improved dosimetry of 64Cu-labeled FPLC purified
      BAT-2IT-1A3-F(ab')2 should more readily allow this agent to be investigated
      clinically to image colorectal cancer using PET.

PMID- 7738664
TI  - Assessing intratumor distribution and uptake with MBBG versus MIBG imaging and
      targeting xenografted PC12-pheochromocytoma cell line.
AB  - The heterogeneity of tumor uptake is likely to substantially limit the
      effectiveness of metaiodobenzylguanidine (MIBG) therapy. This study was done to
      establish whether metabromobenzylguanidine (MBBG) can target neuroendocrine
      tumors and to provide intratumor biodistribution and uptake information in
      comparison to MIBG. METHODS: MBBG and MIBG tumor uptake and kinetic studies were
      performed in experimental PC-12 pheochromocytoma grown in nude mice. Intratumor
      distribution studies were performed using autoradiography and secondary ion mass
      spectrometry (SIMS) microscopy, because the latter technique can detect and
      potentially quantify both drugs concomitantly within the same tumor specimen.
      RESULTS: MBBG uptake in PC12 tumors was early (2 hr) and intense (80% ID/g).
      Retention values were similar for both drugs 24 hr postinjection. At the cellular
      level, MBBG mostly accumulated in the cytosol. At the multicellular level, cells
      exhibited staining, but in many areas, SIMS images of both drugs were not
      spatially correlated. CONCLUSION: MBBG targeted experimental pheochromocytoma
      efficiently with high early uptake values. Bromine-76-MBBG is a promising means
      of imaging and quantifying tumor uptake with PET. Both drugs were localized in
      the cytosol, but the correlation between the two distributions, as assessed by
      the values of the standardized local concentrations, was weak although
      significant multicellularly.

PMID- 7738665
TI  - Pharmacokinetic comparison of direct antibody targeting with pretargeting
      protocols based on streptavidin-biotin binding.
AB  - Several groups are currently investigating antibody pretargeting as a strategy
      for improving radionuclide delivery. Pharmacokinetic modeling of these protocols
      permits analysis of pretargeting protocols under a broad range of possible
      experimental conditions. METHODS: We used previously developed pharmacokinetic
      models to predict the temporal uptake and spatial distribution of directly
      radiolabeled MAb, radiolabeled biotin given after pretargeting with
      streptavidinylated MAb and radiolabeled streptavidin given after pretargeting
      with biotinylated MAb in a microscopic, prevascular tumor nodule. Two dose
      regimens were investigated, as were the effects of internalization and
      degradation of antibody-antigen complexes (24-hr time constant). RESULTS:
      Simulations indicate that the protocol involving streptavidinylated MAb and
      radiolabeled biotin yields higher tumor-to-blood and tumor-to-lung ratios and
      relative exposures than the other protocols. In the absence of antigen
      internalization, the peak average molar concentration and MRT of biotin in the
      tumor nodule is comparable to that of directly radiolabeled MAb, and the spatial
      distribution of radionuclide is more uniform. When antigen internalization
      occurs, the peak average concentration and the MRT in the tumor nodule are lower
      than the corresponding values for directly radiolabeled MAb. CONCLUSION: In the
      absence of antigen internalization, the protocol involving streptavidinylated MAb
      and radiolabeled biotin offers pharmacokinetic advantages over the other two
      protocols.

PMID- 7738666
TI  - Tumor pretargeting: almost the bottom line.

PMID- 7738667
TI  - Measurement of [methyl-carbon-11]thymidine and its metabolites in head and neck
      tumors.
AB  - We made routine measurements of [methyl-11C]thymidine and its metabolites in
      human venous blood in 13 patients with head and neck tumors. METHODS: Patients
      underwent PET imaging 10-30 min after bolus injection. Venous samples were
      collected at various intervals and water-soluble 11C-metabolites were analyzed
      with semipreparative HPLC on a C18 column with isotonic phosphate solution as an
      eluant. RESULTS: After rapid clearance, total radioactivity remained constant at
      a level of about 1.2% of the initial injected activity. CONCLUSION: In this group
      of patients with head and neck cancers, our results show that kinetic differences
      in various 11C-metabolites are small.

PMID- 7738668
TI  - Optimum scanning protocol for FDG-PET evaluation of pulmonary malignancy.
AB  - FDG-PET can differentiate benign from malignant focal pulmonary opacities. We
      performed dynamic FDG-PET studies to determine the optimum time for emission data
      acquisition. METHODS: Patients with focal pulmonary abnormalities demonstrated by
      biopsy to be malignant (n = 10) or benign (n = 4) were evaluated with dynamic FDG
      PET. Dynamic PET data were acquired as sequential 5-min images for 2.5 hr.
      Radioactivity concentration measurements of the focal abnormality, a similar area
      in the opposite lung, and both lungs in the field of view were made throughout
      the period of acquisition. Standardized uptake ratios (SUR) of the lesions were
      calculated. SUR data and lesion-to-background ratios were plotted. The time that
      the SUR provided the maximum separation between benign and malignant masses after
      FDG administration was determined. RESULTS: The SUR values provided the greatest
      separation between benign and malignant abnormalities beginning at 50 min and no
      advantage was identified in imaging later. Achievement of a 4:1 lesion-to
      background ratio occurred by 50 min in malignant lesions. CONCLUSION: The
      acquisition of the emission data used in the evaluation of pulmonary malignancy
      should begin approximately 50 min after FDG administration.

PMID- 7738669
TI  - Dosimetric optimization of postproduction neutron-activated erbium-170-oxide
      enriched pancreatin.
AB  - The feasibility of postproduction neutron activation of an enteric-coated
      pancreatic enzyme preparation for in vivo gastric emptying studies has been
      investigated. METHODS: During production of this multicomponent preparation,
      small amounts of 170Er-enriched erbium oxide, suitable for neutron activation,
      were added. RESULTS: Postproduction neutron irradiation of the labeled
      preparation resulted in short-lived (7.5 hr) gamma-emitting 171Er. Various
      radiocontaminants, however, are produced also. Because of variations in
      activation yields, half-lives, decay schemes and radiotoxicities, both major and
      trace constituents were considered for optimization of both dosimetry and the
      diagnostic measurement. Conditions were optimized for the best ratio of the
      committed dose equivalent due to 171Er to the total committed dose equivalent.
      CONCLUSION: The results show that postproduction neutron activation of a 170Er
      enriched multicomponent preparation can be performed safely within the guidelines
      set by the WHO for experiments in humans involving radioactive materials.

PMID- 7738670
TI  - Potential role of FDG-PET imaging in understanding tumor-host interaction.
AB  - Population ecology mathematical models of tumorigenesis have been developed to
      define the cellular characteristics which allow a transformed population to begin
      as a single individual but end with complete destruction of the host. To invade
      and expand, a tumor population must compete successfully with normal cells for
      space and critical, shared substrate such as glucose. This study uses population
      ecology models to examine the potential role of competition for glucose in tumor
      biology and its implications for FDG-PET imaging. METHODS: Chemostat population
      ecology mathematical models of the tumor-host interface are developed resulting
      in coupled, nonlinear differential equations which link population growth to
      acquisition and utilization of glucose. RESULTS: The models demonstrate that
      increased FDG uptake in tumors observed on PET imaging is the result of increased
      consumption necessary to provide surplus energy for reproduction when inefficient
      glycolytic pathways are used for glucose metabolism. Specific parameters of the
      glucose consumption curves are predicted to be markedly different in normal and
      neoplastic tissues and critical to the tumor-host interaction. Tumor invasability
      and patient prognosis can be linked to these parameters. CONCLUSION: The
      mathematical models link FDG-PET imaging with processes fundamental to the
      outcome of the tumor host interaction. The value of FDG-PET can be expanded by
      quantitation of glucose uptake parameters which will be highly specific in tumor
      detection and strong indicators of tumor aggressiveness. Therapeutic modalities
      designed to decrease tumor glucose uptake or increase glucose uptake in normal
      tissue could be directed and monitored by FDG-PET.

PMID- 7738671
TI  - Liver involvement in lymphoma: role of gallium-67 scintigraphy.

PMID- 7738672
TI  - Daphne Anderson Roe (1923-1993).

PMID- 7738673
TI  - Induction of pancreatic growth and proteases by feeding a high amino acid diet
      does not depend on cholecystokinin in rats.
AB  - We examined differences in pancreatic growth, enzyme content and enzyme
      concentration between rats fed diets containing normal (2.49 g nitrogen/kg diet)
      or high (7.46 g nitrogen/kg diet) levels of an amino acid mixture and those in
      rats fed diets containing normal and high levels of casein for 11 d. Rats fed
      these diets were injected with a potent cholecystokinin antagonist, MK-329 (2.5
      mg/kg body wt.d) or with vehicle only. Pancreatic contents (units in pancreas per
      100 g body wt) of protein, trypsinogen and chymotrypsinogen were greater in rats
      fed a high amino acid diet compared with those in rats fed a normal amino acid
      diet. Proportionate increases in protein and the serine proteases in pancreata of
      the high amino acid group relative to those of the normal amino acid group were
      comparable to those of the high casein group relative to the normal casein group.
      The pancreatic protease concentrations (units/g pancreas) of rats fed the high
      casein diet and treated with MK-329 were lower than in rats fed high casein but
      not treated with MK-329. This difference was not observed in rats fed the high
      amino acid diet. These results demonstrate that pancreatic growth and proteases
      are induced by dietary amino acids in rats, and the stimulatory effects of amino
      acids on exocrine pancreas do not depend on cholecystokinin.

PMID- 7738674
TI  - High protein diet has beneficial effects in murine muscular dystrophy.
AB  - In normal muscle there is a delicate balance between muscle protein synthesis and
      protein degradation. It is believed that this balance is disturbed in muscular
      dystrophy (MD) by decreased muscle protein synthesis and/or increased muscle
      protein degradation, resulting in net catabolism. In an attempt to reduce or
      reverse this catabolism, a high protein diet (HPD, 50% protein) was fed to
      dystrophic mice (129/ReJ dy) for 4 wk. The effects on muscle biochemistry, muscle
      function and muscle morphology were compared with those in dystrophic mice fed a
      normal diet (NPD, 20% protein) and in nondystrophic mice (NORM) also fed the 20%
      protein diet. Compared with NORM mice, NPD mice demonstrated greater rates of
      muscle protein synthesis (P < 0.05) as measured by the incorporation of labeled
      phenylalanine into muscle, greater protein degradation (P < 0.01) as measured by
      urinary 3-methylhistidine excretion, and lower muscle protein concentration (P <
      0.01). When dystrophic mice were fed HPD for 4 wk, protein degradation was lower
      (P < 0.01) and muscle protein concentration greater (P < 0.01) than in NPD mice.
      These biochemical improvements were accompanied by greater morphological
      uniformity of muscle fibers, higher volume density of muscle fibers per unit area
      of muscle (P < 0.01), and lower shape factor (P < 0.01). Functionally, HPD led to
      improved muscle endurance (P < 0.01) and increased hind-limb utilization (P
      0.01). We conclude that in murine dystrophy, HPD decreases net muscle catabolism,
      principally by decreasing muscle protein degradation, resulting in improvement in
      muscle morphology, strength and function.

PMID- 7738675
TI  - Physiological doses of oral casein affect hepatic glycogen metabolism in normal
      food-deprived rats.
AB  - In a previous study, administration of casein hydrolysate to food-deprived rats
      at a dose of 4 g/kg body wt resulted in an increase in portal plasma glucagon
      concentration. This was associated with an activation of phosphorylase a and a
      decrease in hepatic glycogen concentration. The present study was undertaken to
      determine whether similar results would be obtained with smaller doses. Doses of
      1 and 2 g/kg body wt were administered to food-deprived rats. At a dose of 2
      g/kg, portal plasma glucagon concentration was significantly elevated. This was
      associated with a slight increase in phosphorylase a activity (P < 0.05) and a
      50% decrease in hepatic glycogen concentration (P < 0.01). At a dose of 1 g
      casein hydrolysate/kg body wt, changes in portal plasma glucagon concentration,
      phosphorylase a activity and hepatic glycogen concentration generally were not
      observed. Hepatic glucose, uridine diphosphoglucose, ATP and glucose-6-phosphate
      concentrations were unaffected by either dose of casein hydrolysate. The data
      indicate a dose-response relationship between casein hydrolysate administration
      and effects on glycogen metabolism in the liver. Protein-induced glycogenolysis
      is likely to occur when rats ingest a moderate amount of a pure protein meal.

PMID- 7738676
TI  - Supplemental dietary cystine elevates kidney metallothionein in rats by a
      mechanism involving altered zinc metabolism.
AB  - Dietary sulfur-containing amino acids influence zinc and copper status. This
      study was conducted to investigate the relationship between the status of these
      elements and tissue metallothionein in rats fed diets supplemented with sulfur
      containing amino acids. In a series of experiments, a diet containing 100 g
      casein/kg diet was unsupplemented or supplemented with L-cystine (3-50 g/kg diet)
      or L-methionine (3 or 30 g/kg diet). Kidney concentrations of zinc and copper in
      rats fed the diet supplemented with high levels of cystine (25 or 50 g/kg) were
      significantly higher than those in rats fed the unsupplemented diet. Kidney
      concentrations of metallothionein and metallothionein mRNA were also
      significantly higher in rats fed cystine-supplemented diets. There was a
      correlation (r = 0.838, P < 0.01) between the levels of zinc and metallothionein
      in kidney of rats fed the diets with different levels of cystine and zinc.
      However, in the rats fed the diets with different levels of cystine and copper,
      the correlation was not as strong (r = 0.587, P < 0.01). The changes in kidney
      metallothionein concentration due to the addition of 3 or 30 g/kg cystine were
      associated with parallel changes in serum zinc concentration and in apparent
      absorption of zinc, but not in serum copper concentration or apparent absorption
      of copper. Addition of 3 or 30 g methionine/kg diet to the diet did not affect
      kidney concentrations of metallothionein or zinc. These results indicate that
      supplementation of cystine to the diet can induce kidney metallothionein through
      a mechanism involving altered zinc metabolism.

PMID- 7738677
TI  - Differential fatty acid accretion in heart, liver and adipose tissues of rats fed
      beef tallow, fish oil, olive oil and safflower oils at three levels of energy
      intake.
AB  - To examine interactive effects of dietary fatty acid composition and energy
      restriction on tissue fatty acid accretion, mature rats consumed diets containing
      beef tallow, fish oil, olive oil or safflower oil with free access or at 85% or
      68% of free access energy intakes. Restriction was accomplished by adjustment of
      dietary carbohydrate level. After 10 wk, animals were killed, and the fatty acid
      compositions of liver, heart and adipose tissues were examined. Compared with
      animals given free access to diets, body weight gains were reduced at wk 10 in
      fish oil- and olive oil-fed groups consuming 85% (P < 0.01) and in all groups
      consuming 68% (P < 0.005) of free access energy intake. Liver and heart weights
      were also lower (P < 0.05) in all groups restricted to 68% of free access energy
      intake. The type of dietary fat and the level of energy restriction influenced
      fatty acid composition in all three tissues at wk 10. In liver tissue, graded
      energy restriction increased (P < 0.02) proportions of stearic acid and decreased
      (P < 0.03) those of palmitic acid. In heart tissue, palmitic acid levels
      decreased (P < 0.01) with energy restriction. In adipose tissue, significant
      energy restriction-related changes in fatty acid composition varied with type of
      fat consumed. These results emphasize the importance of whole-body energy balance
      in addition to dietary fatty acid supply in utilization of dietary fatty acids
      for tissue deposition vs. oxidation.

PMID- 7738678
TI  - Diet and disease alter phosphoinositide composition and metabolism in murine
      polycystic kidneys.
AB  - Because diet can affect the progression of polycystic kidney disease (PKD) and
      because renal phosphoinositide metabolism is altered in mice with PKD, the
      effects of diet and disease on phosphoinositide composition and metabolism were
      examined in kidneys of mice with PKD. The phosphatidylinositol-phosphate (PIP) to
      phosphatidylinositol (PI) molar ratio was higher (0.034 +/- 0.003 vs. 0.023 +/-
      0.001, P < 0.01) and the PI-bisphosphate (PIP2) to PIP molar ratio was lower
      (0.70 +/- 0.08 vs. 1.19 +/- 0.10, P < 0.05) in kidneys of mice with PKD [DBA/2FG
      pcy (pcy)] compared with normal controls (DBA/2J). When initial incorporation
      (reflecting synthesis) of [3H]inositol into renal phosphoinositides in mice
      injected with [3H]inositol was measured, the [3H]PIP to [3H]PI ratio was higher
      in the diseased kidneys compared with normal kidneys (0.016 +/- 0.001 vs. 0.013
      +/- 0.001, P < 0.05), whereas the [3H]PIP2 to [3H]PIP ratio was not significantly
      different. In a study using dietary manipulations that alter the progression of
      PKD in pcy mice (6 vs. 25% casein and sunflower seed oil vs. fish oil in a 2 x 2
      design), animals were injected intraperitoneally with [3H]inositol 5 h before
      killing. In these animals, the [3H]PIP2 to [3H]PIP ratio seemed to be the best
      indicator of disease progression. In addition, kidney weight (as altered by diet)
      was positively correlated (r = 0.62, P = 0.02) with the level of the [3H]PI-3-P
      isomer relative to total [3H]PIP in the kidney. These results demonstrate that
      alterations in dietary protein level and lipid composition can modulate renal
      phosphoinositide signal transduction in mice with PKD.

PMID- 7738679
TI  - The combined effects of dietary fat and estrogen on survival, 7,12
      dimethylbenz(a)anthracene-induced breast cancer and prolactin metabolism in rats.
AB  - The relationships between dietary fat concentration (10 or 40% of energy), fat
      source (corn oil or beef tallow) and estrogen (control, ovariectomy or
      ovariectomy with estrogen replacement) to 7,12-dimethylbenz(a)anthracene (DMBA)
      induced breast carcinogenesis and survival in rats were studied in a 2 x 2 x 3
      factorial experiment. Female Sprague-Dawley rats given DMBA (2.5 mg/100 g body
      wt, intragastric) at 55 d of age were randomly allocated to three groups 48 h
      later: sham ovariectomy (control), ovariectomy (OVX) or ovariectomy with a
      subcutaneous estrogen implant (OVX+E). Each group was subdivided into dietary
      groups fed 10 and 40% of energy as corn oil or beef tallow for 70 wk. OVX+E rats
      exhibited serum estrogen concentrations in excess of physiologic values. Survival
      at 70 wk for the 3 hormonal groups was control 51%, OVX 67% and OVX+E 13%.
      Mortality in controls was doubled by feeding a high fat diet; no diet effect was
      detected in OVX or OVX+E rats. Palpable tumors developed in 74, 14 and 60% of
      control, OVX and OVX+E rats, respectively. High fat diets approximately doubled
      the hazard of developing a palpable tumor. Adenocarcinoma prevalence was 58, 12
      and 63% in control, OVX and OVX+E rats, respectively. The odds of having any
      tumor, an adenocarcinoma or an adenoma were multiplied by 3.6, 2.8 and 2.3,
      respectively, for rats fed high vs. low fat. Additional studies showed that diet
      had no effect on serum prolactin or estrogen concentrations or metabolism and
      clearance of intravenously administered radiolabeled prolactin. We demonstrated
      that high dietary fat concentration enhances breast carcinogenesis independently
      of cyclic ovarian function, although the presence of estrogen may be a
      prerequisite for significant dietary modulation. The effect of fat on breast
      cancer is not mediated by major changes in systemic prolactin metabolism.

PMID- 7738680
TI  - Dietary magnesium deficiency in rats enhances free radical production in skeletal
      muscle.
AB  - Recent studies suggest that free radicals may be involved in tissue injuries
      induced by magnesium deficiency. The aim of the present study was to assess the
      effect of magnesium deficiency on free radical production of skeletal muscle
      tissue. Male Wistar rats were pair-fed from weaning for 12 d either control or Mg
      deficient diets containing 960 or 40 mg magnesium/kg diet, respectively. In the
      Mg-deficient rats, hypomagnesemia was accompanied by significantly lower
      magnesium and greater calcium concentrations in skeletal muscle tissue. Electron
      microscopy of skeletal muscle tissue revealed ultrastructural changes, including
      swelling mitochondria and disorganization of the sarcoplasmic reticulum network.
      Using the spin-trapping technique, we showed that significantly more hydroxyl
      radicals were generated in muscle homogenates of Mg-deficient rats. Moreover, the
      amount of spin trap adducts was increased in the presence of exogenous iron in
      both groups. In agreement with these observations, a greater concentration of
      thiobarbituric acid-reactive substances and a lower concentration of thiol groups
      were found in skeletal muscle of the Mg-deficient group compared with controls.
      These results strongly support the hypothesis that free radical-mediated injury
      could contribute to skeletal muscle lesions resulting from magnesium deficiency.

PMID- 7738681
TI  - Dietary vitamin A intake and the incidence of diarrhea and respiratory infection
      among Sudanese children.
AB  - The relationship of vitamin A deficiency and child survival has been documented
      in a number of studies but not in others, yet the relationship of vitamin A with
      child morbidity remains controversial. We prospectively examined the relationship
      of dietary vitamin A intake and the incidences of diarrhea and respiratory
      infection among 28,753 Sudanese children between the ages of 6 mo and 6 y. Total
      dietary vitamin A intake was strongly and inversely associated with the risk of
      diarrhea (multivariate risk in top relative to bottom quintile = 0.58, 95%
      confidence interval = 0.47-0.72); we also observed a strong inverse association
      with the risk of having cough and fever (0.60, 0.45-0.81). On the other hand, we
      noted a significantly positive association of dietary vitamin A intake and
      incidence of cough alone (1.69, 1.52-1.88), a sign that may be assocsated with a
      healthy respiratory epithelium. Vitamin A intake was also negatively associated
      with the risk of measles. These prospective data emphasize the importance of
      adequate dietary vitamin A intake to protect the health of children in developing
      countries.

PMID- 7738682
TI  - Length screens better than weight in stunted populations.
AB  - Stunting (low length-for-age) is the most widespread manifestation of growth
      retardation worldwide. Yet, most nutrition programs use weight-for-age for
      screening of at-risk children. This study tested whether weight-for-age was an
      effective screening tool in a severely stunted rural Guatemalan population, using
      data from the INCAP longitudinal supplementation trial (n = 400). Stunting was
      defined as length-for-age < -2 SD of the National Center for Health Statistics
      standards at 3 y of age. Sensitivity and specificity analyses and receiver
      operating characteristics curves were used to compare weight indicators (weight
      for-age, weight velocity and weight-for-length) with length (length-for-age and
      length velocity) and arm and head circumferences measured during early infancy.
      Length indicators were clearly superior to weight in predicting stunting (Zda
      test), and velocities were consistently worse than attained growth. Length-for
      age at 6 mo had the best performance, followed by length-for-age at 3 mo, and
      weight-for-age at 6 and at 3 mo. Velocities, weight-for-length and circumferences
      were all poor predictors of stunting. Using the cutoff of < -1 SD, length-for-age
      at 3 mo was the best screening indicator for the early detection of growth
      faltering. Thus, the current use of weight-for-age, which results in large
      proportions of at-risk children being missed by screening, greatly limits the
      potential for impact of nutrition interventions.

PMID- 7738683
TI  - Nutrients, body composition and exercise are related to change in bone mineral
      density in premenopausal women.
AB  - This study determined relationships among total energy intake, nutrient intake,
      body composition, exercise group status, and annual rates of change (slopes) in
      bone mineral density in 66 Caucasian premenopausal women (mean age, 34.4 +/- 2.7)
      taking calcium supplements. Body composition components measured by dual-energy X
      ray absorptiometry included fat mass, soft tissue lean mass, and bone mineral
      density (g/cm2) of total body, spine (lumbar vertebrae 2-4), and three femur
      sites measured at baseline, 5, 12, and 18 mo. Nutrients were not significant
      variables in regression models predicting bone mineral density slopes (rates of
      change) at any femur site. The only significant variable in models predicting
      Ward's triangle bone mineral density slope was the initial fat mass and, for
      trochanter, exercise. Significant variables (P < 0.05) in models predicting total
      body bone mineral density slope included the initial fat mass and fat mass slope
      plus either vitamin A, carotene, fiber, magnesium, or phosphorus (R2 from 0.31 to
      0.25) and fat mass slope plus sodium (R2 = 0.24). The significant variable in the
      model predicting L2-4 slope was energy intake (R2 = 0.17, P < 0.05). We conclude
      that nutrient intake, exercise, and body composition are related to bone mineral
      density rate of change and that relations among these variables vary by bone
      site.

PMID- 7738685
TI  - Characterization of the Japanese quail oocyte receptor for very low density
      lipoprotein and vitellogenin.
AB  - The plasma membrane receptor for VLDL and vitellogenin from oocytes of Japanese
      quail (Coturnix coturnix japonica) was characterized and compared with that of
      another domestic fowl, the chicken (Gallus domesticus). When visualized by ligand
      blotting with biotinylated or 125I-labeled lipoproteins, the quail
      VLDL/vitellogenin receptor had an apparent M(r) of 95 kDa under nonreducing
      conditions, identical to that of the chicken receptor. Upon analysis by ligand
      blotting, binding of radiolabeled quail plasma VLDL to the quail oocyte receptor
      seemed to be saturable and exhibited high affinity (apparent Kd of 13.9 mg/L).
      Cross-reactivity, at the level of ligand recognition, was observed between quail
      and chicken VLDL/vitellogenin receptors, and immunological relatedness was
      demonstrated by Western blotting with a rabbit anti-chicken oocyte VLDL receptor
      antibody. In contrast, a species difference was observed in the apolipoprotein
      VLDL-II moiety of plasma VLDL. Chicken apolipoprotein VLDL-II, an 82-amino acid
      protein with a disulfide crosslink at residue 75 (the sole cysteine residue),
      existed as a homodimer of 9.5 kDa subunits and, to a lesser extent, as a monomer.
      Quail apolipoprotein VLDL-II existed only in monomeric form without reduction and
      lacked cysteine. The present results demonstrate that, despite a difference in an
      apolipoprotein moiety of VLDL, quail and chicken oocyte lipoprotein receptors
      share key structural and functional elements. This lends further support to the
      notion that receptor recognition is mediated by the common VLDL component,
      apolipoprotein B.

PMID- 7738684
TI  - 15N-labeled immunoglobulins from bovine colostrum are partially resistant to
      digestion in human intestine.
AB  - To evaluate true ileal digestibility of bovine immunoglobulins, seven healthy
      human adults ingested a 15N-labeled preparation of an immunoglobulin concentrate.
      After fasting overnight, subjects drank 400 mL of immunoglobulin concentrate (77
      mmol), and ileal effluents were collected for 8 h at 20-min intervals using a
      naso-intestinal intubation technique. In addition to osmolality and pH, the
      concentrations of exogenous and endogenous nitrogen and ions (Na+, K+, Cl-, Ca2+,
      Mg2+) in the effluents were measured. Bovine immunoglobulin concentrations (IgG,
      IgM, IgA) were estimated by a radial immunodiffusion technique. The mean flow
      rate of the liquid phase was 22.3 +/- 6.1 mL/20 min and did not vary
      significantly during the collection period. No change was observed for
      osmolality, pH or Na+, K+ and Cl- concentrations. Two hours after meal ingestion,
      Ca2+ and Mg2+ concentrations increased significantly (P < 0.05). The recoveries
      of nitrogen of ingested IgG and IgM still immunologically active were 19 +/- 3%
      and 19 +/- 4%, respectively. No IgA was detected in the ileum. Mean digestibility
      of the exogenous nitrogen fraction was 79 +/- 3%. In comparison to literature
      data, which show that other milk proteins have ileal digestibilities of > 90%,
      our results demonstrate a lower ileal digestibility of bovine immunoglobulins in
      humans.

PMID- 7738686
TI  - Dietary intake of the short-chain triglyceride triacetin vs. long-chain
      triglycerides decreases adipocyte diameter and fat deposition in rats.
AB  - Diets containing either triacetin (the water-soluble triglyceride of acetate) or
      long-chain triglycerides (LCT) were fed to rats for 30 d to determine the effect
      on body weight gain and adipose tissue cellularity. Male Sprague-Dawley rats were
      allowed free access to one of three diets: a control diet containing 5% of energy
      as fat or one of two experimental diets that contained 30% triglyceride (by
      energy). The source of the triglyceride in the two experimental groups was either
      100% LCT or 95% triacetin + 5% LCT. Within the experimental groups receiving 30%
      fat, the source of dietary triglyceride (LCT vs. triacetin) did not affect total
      energy consumption. There were no significant differences in body weight at the
      onset of the study; however, animals fed 100% LCT weighed significantly more than
      the other two groups at the end of the study. In all three fat pads studied,
      animals fed triacetin had significantly lower pad mass than did animals fed LCT.
      Mean fat cell size was smaller in fat depots of animals fed short-chain
      triglyceride. Provision of dietary energy as the short-chain triglyceride
      triacetin in lieu of LCT resulted in lower weight gain and fat deposition. These
      data demonstrate the impact of dietary triglyceride composition on body weight
      regulation.

PMID- 7738687
TI  - Zinc absorption estimated by fecal monitoring of zinc stable isotopes validated
      by comparison with whole-body retention of zinc radioisotopes in humans.
AB  - Knowledge about zinc availability from human diets is limited due to
      methodological difficulties. Recently developed stable isotope techniques for
      estimating dietary zinc absorption were compared with radioisotope techniques in
      five men and three women. Stable and radioactive zinc isotopes were
      simultaneously administered. Fecal excretion of the isotopes as well as whole
      body retention of the radioactive zinc isotope was monitored. Concentration of
      stable zinc isotope label in fecal samples was determined by inductively coupled
      plasma mass spectrometry by fully quantitative measurements and from inductively
      coupled plasma mass spectrometry isotope ratios combined with analysis of total
      zinc content using atomic absorption spectrometry. Zinc absorption estimated from
      whole-body retention was 27 +/- 6% (mean +/- SD), estimated zinc absorption
      obtained by fecal monitoring of radioisotope was 26 +/- 9%, and the two stable
      zinc measurements resulted in values of 29 +/- 12 and 33 +/- 12%, respectively.
      There was no significant difference in zinc absorption estimated from whole-body
      retention and with the fecal monitoring methods. Recovered stable zinc isotope
      label was significantly lower than recovered radioisotope. For individual fecal
      samples, systematic differences of 16% and 12%, respectively (P < 0.05), between
      the radioisotope recovery and the recovery of stable isotopes with the two
      methods for measurement was observed. The stable zinc isotope technique for
      measurement of zinc absorption resulted in mean results similar to those of the
      radioisotope technique, but with a larger variation in the measurements.

PMID- 7738688
TI  - Rat serum osteocalcin concentration is decreased by restriction of energy intake.
AB  - We studied the effects of energy restriction on serum osteocalcin concentration
      and bone formation rate in rats. The experiment was designed to achieve energy
      restriction by reducing the carbohydrate intake while providing identical
      quantities of protein, fat, vitamins and minerals. Energy intakes of three groups
      of post-weaning male rats were restricted by 20, 40 and 60% for 4 wk. Serum
      calcium, phosphorus, transthyretin, triiodothyronine (T3), thyroxine (T4), 1,25
      dihydroxycholecalciferol, 25-hydroxycholecalciferol and immunoreactive
      parathyroid hormone (iPTH) concentrations were determined. Energy restriction
      (20, 40 and 60%) produced a significant and gradual drop of serum osteocalcin
      concentrations, although the serum concentrations of its key regulators, i.e.,
      1,25-dihydroxycholecalciferol and iPTH, were not significantly affected. On the
      contrary, serum concentrations of calcium, phosphorus, transthyretin, T3 and T4
      were significantly lower in the energy-restricted groups. However, our results do
      not support their implication in the regulation of serum osteocalcin synthesis by
      energy intake. Serum osteocalcin concentration was positively correlated with
      bone mineral apposition (r = 0.50, P < 0.05) and bone mineralization (r = 0.50, P
      < 0.05) rates suggesting that its decrease resulted from a reduction of bone
      formation, and not from abnormal mineralization, because osteoid seam thickness
      was not modified. Energy intake seems to be an important determinant of serum
      osteocalcin concentration and bone formation; however, the exact mechanism
      underlying this regulation remains to be determined.

PMID- 7738689
TI  - Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells.
AB  - Differentiated cultures of Caco-2 human colonic cells were used to examine the
      importance of reduction of nonheme ferric iron, Fe(III), for transport across the
      brush border surface. Cultures accumulated approximately 100 pmol Fe/(h.mg
      protein) when 10 mumol Fe(III) as the nitrilotriacetic acid complex (1Fe:2NTA)
      was added to the apical compartment. Ascorbic acid enhanced cellular acquisition
      of iron in a dose-dependent manner, with a concentration as low as 8 mumol/L
      ascorbate increasing iron uptake by 50%. Similarly, the rate of iron transport
      from the apical to the basolateral compartment increased 5.6- and 30-fold when
      100 and 1000 mumol/L ascorbic acid, respectively, were present in the apical
      chamber. Ascorbate-mediated stimulation of iron uptake was temperature dependent
      and required the reduction of Fe(III) to Fe(II), because it was inhibited by
      ascorbate oxidase and chelators of Fe(II). Moreover, Caco-2 cells recycled
      dehydroascorbic acid to ascorbic acid. Ferricyanide and Fe(II) chelators also
      partially inhibited iron uptake from a medium devoid of ascorbic acid. Intact
      Caco-2 cells exhibited a ferrireductase activity on the apical surface that
      accounted for the majority of iron accumulated by cells incubated in the absence
      of exogenous reductant. These data suggest that reduction of Fe(III) within the
      lumen or at the cell surface is required for transfer of this essential
      micronutrient across the intestinal brush border surface.

PMID- 7738690
TI  - A Na(+)-dependent mechanism is involved in mucosal uptake of cinnamic acid across
      the jejunal brush border in rats.
AB  - Phenolic acids are present in all plant-derived foods and in most diets. Indirect
      evidence indicates substantial absorption of phenolic monomers from the
      gastrointestinal tract. However, the mechanisms involved in the absorptive
      process are unknown. The present study investigates mucosal uptake of
      radioactively labeled cinnamic acid as a model substance for monomeric cinnamic
      acid derivatives (e.g., cinnamic, ferulic or caffeic acid) in the rat jejunum
      using an in vitro mucosal uptake technique. The results indicate the existence of
      a Na(+)-dependent saturable transport mechanism for uptake of cinnamic acid
      across the jejunal brush border membrane. The observed Na+ dependence of jejunal
      cinnamate uptake seems not to be related to the activity of the Na+,H+ exchanger.
      Lowering the pH of the incubation medium resulted in a pronounced increase in
      mucosal cinnamate uptake that can be only partially explained by an increase in
      nonionic diffusion of cinnamic acid. Furthermore, jejunal uptake of cinnamate
      seems to be influenced by intracellular HCO3- and/or pH, since the addition of
      methazolamide to a HCO3(-)- and CO2-free incubation medium significantly
      inhibited mucosal cinnamate uptake, whereas methazolamide was without an effect
      in the presence of HCO3- and CO2 in the incubation medium. Unlabeled cinnamic and
      ferulic acid as well as short-chain fatty acids (acetic, propionic and butyric
      acid) significantly inhibited Na(+)-dependent uptake of radioactivity labeled
      cinnamic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738691
TI  - Dietary calcium levels and treatment interval determine the effects of lead
      ingestion on plasma 1,25-dihydroxyvitamin D concentration in chicks.
AB  - The combined effects of dietary calcium level and lead level on several indices
      of vitamin D endocrine function were examined in young, growing chicks. Day-old
      animals fed a nutritionally adequate diet for 2 wk were fed diets either adequate
      (1.2%) or low (0.1%) in calcium, and containing 0, 0.2 or 0.8% lead for an
      additional 1 or 2 wk. In the calcium-adequate group, lead ingestion significantly
      elevated intestinal calbindin-D28k protein and mRNA levels as well as plasma 1,25
      dihydroxyvitamin D concentration compared with the control animals fed a lead
      free diet. The effect was apparent after 1 wk of treatment and continued through
      wk 2. In the calcium-deficient group, the early (1 wk) increases in plasma 1,25
      dihydroxyvitamin D and calbindin-D28k protein and mRNA were significantly
      reversed by lead ingestion over the 2-wk trial period in a dose-dependent
      fashion. In these circumstances, vitamin D endocrine function is severely
      compromised. Therefore, lead ingestion may result in either enhanced or
      diminished circulating 1,25-dihydroxyvitamin D concentrations and ensuing
      intestinal responses, depending of dietary calcium level and the duration of lead
      intake. These results provide possible explanations for several apparently
      conflicting sets of observations regarding lead-calcium interactions.

PMID- 7738692
TI  - Increasing phosphorus intake reduces urinary concentrations of magnesium and
      calcium in adult ovariectomized cats fed purified diets.
AB  - We assessed the phosphorus requirement of adult cats and the relationship between
      phosphorus intake and the fecal and urinary excretion of calcium, magnesium and
      phosphorus. Female cats (ovariectomized at the onset of sexual maturity) were fed
      purified diets containing 4.6, 9.2, 18.4 or 27.7 mmol phosphorus/MJ in a 4 x 4-wk
      crossover study. During the experiment, balance studies were performed and blood
      samples were taken. A dietary level of 4.6 mmol phosphorus/MJ was found to be
      sufficient to maintain phosphorus balance and normal plasma concentrations of
      phosphorus in the adult ovariectomized cats. Increasing levels of dietary
      phosphorus in the form of NaH2PO4.2H2O caused lower urinary pH values, lower
      urinary concentrations of calcium and magnesium, and higher urinary
      concentrations of phosphorus. When dietary levels of phosphorus were raised, the
      percentage of apparent absorption of magnesium was lower, whereas that of
      phosphorus was higher. Although it could be predicted that dietary phosphorus
      levels higher than the National Research Council recommendation of 9.2 mmol/MJ
      markedly reduced urinary struvite saturation, these higher levels are discouraged
      because they are associated with lower plasma phosphorus concentrations and
      creatinine clearance.

PMID- 7738694
TI  - Assessing adequacy of cholecalciferol supplementation in chicks using plasma
      cholecalciferol metabolite concentrations as an indicator.
AB  - Cholecalciferol (vitamin D) deficiency rickets remains an occasional problem in
      poultry. Diagnosis currently relies on analysis of feed and histopathological
      examination of bone. These experiments were designed to provide data that might
      allow diagnosis of cholecalciferol deficiency on the basis of plasma
      concentrations of 25-hydroxycholecalciferol, a circulating metabolite of
      cholecalciferol. Day-old broiler chicks were fed corn-soybean meal or purified
      ingredient cholecalciferol-deficient diets supplemented with 0, 5, 10, 15, 20,
      25, 37.5 or 75 micrograms cholecalciferol/kg diet. Plasma and bone samples were
      collected 21 d later. Chicks fed the unsupplemented purified ingredient diet
      became truly deficient, having no detectable plasma concentrations of the
      cholecalciferol metabolites 25-hydroxycholecalciferol, 1,25
      dihydroxycholecalciferol, or 24,25-dihydroxycholecalciferol. Chicks fed the corn
      soybean meal diet without supplementation had low but detectable concentrations
      of both 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol in plasma.
      Body weight, bone calcium and bone phosphorus concentrations of chicks fed the
      corn-soybean meal diet suggest that the cholecalciferol requirement of broiler
      chicks is at least 10 micrograms/kg diet. At this dietary level of
      cholecalciferol, plasma 25-dihydroxycholecalciferol concentration was 12.5
      nmol/L. One hundred percent of the theoretical maximal response in body weight
      and bone calcium content was seen at 20 micrograms cholecalciferol/kg diet, which
      increased plasma 25-hydroxycholecalciferol concentration to 25 nmol/L in the
      chicks fed the corn-soybean meal diet. These data provide a nomogram of plasma 25
      dihydroxycholecalciferol concentration that can be expected from including
      different concentrations of cholecalciferol in the diet, and also offer a means
      of diagnosing cholecalciferol deficiency in field cases of tickets.

PMID- 7738693
TI  - Age at sexual maturity influences the response of single comb White Leghorn
      pullets to marginal and low levels of dietary phosphorus.
AB  - This study was designed to determine the differences in response of early
      maturing (EM) and late-maturing (LM) Single Comb White Leghorn pullets within a
      flock to marginal or low dietary phosphorus. Various levels of dietary phosphorus
      were fed to EM and LM Leghorn pullets from 18 wk of age until the age of peak egg
      production (24 wk). The dietary phosphorus levels were 0.40, 0.45, 0.50, 0.55 and
      0.70 g total phosphorus (tP)/100 g diet, corresponding to calculated available
      phosphorus values of 0.18, 0.23, 0.28, 0.33 and 0.48 g/100 g, respectively. At
      0.70 and 0.55 g tP/100 g, the plasma inorganic phosphorus, Ca++ and urine calcium
      concentrations did not differ between EM and LM pullets, whereas LM pullets had a
      better bone status than EM pullets as reflected by bone mineral content, bone
      density and bone breaking strength. As dietary phosphorus was lowered from 0.55
      to 0.4 g tP/100 g, the plasma concentration of inorganic phosphorus dropped and
      that of Ca++ increased at greater rates in LM pullets than in EM pullets. The
      magnitude of decline in bone status was also greater in LM than in EM pullets
      when dietary phosphorus was lowered from 0.55 to 0.40 g tP/100 g. The maximum
      incidences of osteoporosis and mortality were observed in LM pullets fed 0.40 g
      tP/100 g followed by LM pullets fed 0.45 g tP/100 g diet. We conclude that when
      early layer diets contain marginal or low levels of phosphorus, the severity of
      adverse effects are greater in LM pullets than in EM pullets.

PMID- 7738695
TI  - Requirements for what? Is the measurement of energy expenditure a sufficient
      estimate of energy needs?

PMID- 7738696
TI  - Protein quality of enteral nutritionals.

PMID- 7738697
TI  - Maintenance requirements for amino acids by rats.

PMID- 7738698
TI  - Assessment of folate methodology used in the Third National Health and Nutrition
      Examination Survey (NHANES III, 1988-1994).

PMID- 7738699
TI  - [Effect of oak pollen on patients with birch pollinosis].
AB  - The author reviewed 53 cases of birch pollinosis treated in our ENT-clinic
      between 1990 and 1991. Of interest is the fact that many of these patients
      complained of typical symptoms in and after June, when birch pollen has usually
      disappeared. We considered this discrepancy to be attributable to the effects of
      grass pollen, one of the common causal agents in this period. However, only a few
      patients tested positive for grass pollinosis. We therefore postulated that cross
      reactivity between birch and oak pollen accounted for this phenomenon, because
      both trees belong to same order, Fagales. A strong correlation between RAST
      scores for birch and oak pollen was detected, and the oak pollen RAST score was
      significantly reduced by birch pollen extract in an inhibition test. These
      findings demonstrated actual cross-reactivity between birch and oak pollen. Birch
      pollinosis patients in Sapporo therefore have allergic symptoms from March to
      July.

PMID- 7738700
TI  - [Abnormal sensation in the throat and autonomic nerve dysfunction symptoms].
AB  - Abnormal sensations, such as a lump, itchiness or choking, in the throat (AST)
      may develop as symptoms of autonomic nerve dysfunction (AND). If this is true,
      the subjects with AST should show more subjective symptoms and objective signs of
      AND than those without AST. We classified 500 otolaryngological and neurological
      patients [172 males and 328 females, age 58.4 +/- 14.0 years (mean +/- SD)] with
      various signs and symptoms suggesting autonomic nerve dysfunction into 2 groups:
      370 patients with AST (AST group) and 130 without AST (non-AST group). For the
      subjective evaluation of AND symptoms, we calculated the number of positive
      answers to 33 questions concerning AND symptoms which appear in the Cornell
      Medical Index (Health Questionnaire). Objective evaluation of AND was done by
      analyzing the coefficient of variation (%) of 100 R-R intervals on
      electrocardiograms [CV R-R (%)], as previous studies by others have shown that CV
      R-R (%) decreases with age and/or with the severity of autonomic nerve
      dysfunction. The following results were obtained in the comparison between the
      two groups. 1) There were significantly more complaints of AND symptoms in the
      AST group (7.3 +/- 5.5, mean +/- SD) than in the non-AST group (5.3 +/- 4.4) (p <
      0.0005 by Wilcoxon test). 2) The relative CV R-R (%) value calculated by dividing
      the CV R-R (%) actually obtained by the formula [5.13 - 0.0419 x age of subject
      (years)] was significantly smaller in the AST group (0.98 +/- 0.40) than in the
      non-AST group (1.06 +/- 0.39) (p < 0.05 by Wilcoxon test).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7738701
TI  - [Distortion-product otoacoustic emissions in kanamycin-treated guinea pig
      cochlea].
AB  - Measurement of distortion-product otoacoustic emissions (DPOAE) is widely
      accepted as one of the most valuable tools for evaluating the frequency of
      specific cochlear pathology. Previous studies have revealed that distortion
      product levels in the ear canal are definitely correlated with degree of damage
      in the cochlea. However, there seem to be no clear data of help in predicting the
      distribution and grade of damage in the cochlea quantitatively on the basis of
      the results of this non-invasive test. The present study is designed to assess
      correlations between degree of outer hair cell (OHC) damage by a potent ototoxic
      antibiotic, kanamycin, and DPOAE levels at the characteristic frequency at the
      site. Guinea pigs were used after daily intramuscular administration of kanamycin
      for 7 or 10 days. DPOAE levels were measured using a system (CUBDIS: Etymotic
      Research) with 78 frequency combinations of iso-intensity primaries from 0.5kHz
      to 16kHz of f2. The frequency ratio (f2/f1) was set at 1.2. Distortion-product
      level plots versus f2 (DP-grams) were constructed. The integrity of the OHC
      system was evaluated histologically by the succinic dehydrogenase (SDH) method
      under a light microscope. Cochleograms were constructed by calculating
      percentages of intact OHCs along the basilar membrane in 1-mm blocks. The DP
      grams and the histopathological cochleograms showed essentially identical
      patterns in the kanamycin-damaged guinea pig cochlea. The results suggest that:
      1) The generation of DPOAE requires functioning OHCs. 2) DPOAE measurement
      provides information allowing prediction of OHC damage distribution in the
      cochlea without histological investigations. 3) Careful setting of primary levels
      and other parameters is necessary to reliably predict the pathology. 4) Attempts
      to detect of minimal OHC damage could fail. 5) DPOAE seem very useful for
      monitoring cochlear function in clinically.

PMID- 7738702
TI  - [Meniere's disease in the aged].
AB  - Twenty-one patients with Meniere's disease over the age of seventy years were
      classified into two groups. Group I: Eleven patients who had their first
      vertiginous attack after the age of sixty-nine (nine males, two females). Group
      II: Ten patients who had a long history of Meniere's disease and had been
      followed until the age of 72 to 79 years of age (seven males, three females). In
      Group I there were repeated attacks of vertigo accompanied by fluctuations in
      hearing in the low and middle tone range, though not so severe or frequent as in
      the typical active stage of Meniere's disease in younger patients. Most patients
      in this group were still working as managers of a company or institution. Other
      patients had been taking care of a sick spouse for several years. In Group II,
      the patients rarely experienced severe vertiginous attacks, however, hearing
      became rapidly impaired in most cases after they reached around 70 years of age.
      Progression of their hearing impairment was so severe that it was considered
      beyond the loss of acoustic function attributable to physiological aging. The
      importance of Meniere's disease among the aged is increasing as a result of the
      rapid increase in the aged population. Based on long-term observations of
      Meniere's disease, we have concluded that there are at least two clinically
      different types of disease in the aged, then especially age of onset and the
      duration of the disease of the each patient must be heeded.

PMID- 7738703
TI  - [Motor innervation of the guinea pig arytenoid muscle from the standpoint of the
      reinnervation process].
AB  - The innervation pattern of the arytenoid muscle (AR) was studied from the
      standpoint of the reinnervation process in 32 guinea pigs with typical unpaired
      AR. In 26 animals the muscle was denervated by cutting the left recurrent
      laryngeal nerve (RLN). The superior laryngeal nerve was also transected to
      eliminate the possibility of reinnervation from this nerve. Both light and
      electron-microscopic examinations in 18 denervated animals and 4 normal animals,
      and a glycogen depletion experiment in 8 denervated animals and 2 normal animals
      were carried out on the AR and the posterior cricoarytenoid muscle (PCA). 1.
      Light microscopic study: Anastomosis with arytenoid branches from the
      contralateral RLN was observed in the belly of AR. Half of the myelinated fibers
      in the intramuscular nerve funiculus remained degenerated as of seven days after
      transection. After three weeks, degeneration of the myelinated fiber was no
      longer seen, and the number of myelinated fibers had been restored to within the
      normal range. The muscle fibers of the left PCA degenerated completely, while
      those of the AR remained intact. 2. Electron-microscopic study. Three days after
      transection, the nerve terminals of half of the neuromuscular junctions (NMJs)
      were absent in the AR. Seven days after transection, however, both myelinated and
      unmyelinated fibers were recognized in the intramuscular nerve funiculus. Half of
      the NMJs in the AR were normal, one fourth had degenerated and the rest had
      regenerated. Five weeks after transection, no degeneration or regeneration of the
      NMJs was seen. Unmyelinated fibers were no longer found in the intramuscular
      funiculus. 3. Glycogen depletion experiment: As of three weeks after transection,
      half of the AR fibers stained with PAS despite electrical stimulation of the
      contralateral (right) RLN. Five weeks after transection, none of the AR fibers
      stained. Thus, all of the AR fibers appeared to have been the result of
      reinnervation from the contralateral RLN. The results of the present study
      indicate that transection of the unilateral RLN facilitates collateral sprouting
      from the contralateral RLN in guinea pigs. This collateral sprouting occurring
      between 3 and 7 days following denervation reinnervated the denervated muscle
      fibers before degeneration. Collateral sprouting branches may easily extend into
      adjacent denervated Schwann's sheaths, since the arytenoid branch of the RLN runs
      in contact with that of the contralateral RLN in the identical intramuscular
      nerve funiculus. Although each muscle fiber in the AR is innervated unilaterally,
      this unpaired muscle as a whole receives specific motor innervation from both
      RLNs.

PMID- 7738704
TI  - [Indications for endoscopic sinus surgery. A clinical study on patients with a
      poor post-operative course].
AB  - One hundred and fifty-three patients with chronic sinusitis underwent endoscopic
      endonasal sinus surgery. They were preoperatively evaluated on the basis of their
      complaints, the severity of nasal polyps, X-ray findings, and axial and/or
      coronal CT scans. Postoperative degree of improvement in their complaints and
      endoscopic findings in the nasal cavity and sinus cavities were assessed. Most
      patients, including those with severe maxillary sinusitis, had a good
      postoperative course. The percentage of improvement in their complaints was
      99.3%. Even in the case of olfactory disturbance, which is the most difficult
      symptom to treat, the percentage of improvement was 81.0%. There were only 8
      patients with complaints and pathological findings in their nose or sinuses after
      the operation, 4 with allergic rhinitis and/or asthma, 1 with severe inflammation
      of the olfactory cleft, 1 with thickening of the bone in the sinuses after a 25
      year history of sinusitis without treatment, and 2 with narrowing of the
      antrostoma at the middle meatus after the operation.

PMID- 7738706
TI  - [A case of extramedullary plasmacytoma of the epipharynx--pathological diagnosis
      using multiple supplementary methods].
AB  - A rare case of extramedullary plasmacytoma of the epipharynx is reported. A 76
      year-old woman presented with a one-year history of postnasal drip. Physical
      examination revealed a mass lesion in her epipharynx without cervical lymph node
      swelling. Biopsy of the mass showed diffuse proliferation of plasma cells at the
      light and electron microscopic levels. Immunohistochemical examination
      demonstrated monoclonal exhibition of IgA and kappa-light chain in the tumor
      cells. Furthermore, in flow cytometric analysis, the tumor cells were found to be
      CD10- CD19- CD20- CD22- HLA-DR- CD38++ sIg- EMA+, a typical phenotype of
      plasmacytoma. Additionally, rearranged bands were identified in Southern blot
      analysis of the tumor extract using probes for immunoglobulin heavy chain and
      kappa-light chain. Serum myeloma-protein and urine Bence-Jones protein were
      negative. Bone marrow examination, X-ray examination, CT scanning and 67Ga- and
      99mTc-scintigrams showed no other systemic lesions. She received irradiation of
      58 Gy to the epipharyngeal area over 7 weeks, followed by transnasal endoscopic
      resection using KTP/532 laser. The patient is free of disease six months after
      surgery, and is currently under close follow-up.

PMID- 7738705
TI  - [Differentiation between allergic rhinitis and vasomotor rhinitis by
      electrophoretic evaluation of the protein in pituita].
AB  - Application of trichloro-acetic acid (TCA) to the inferior turbinates is being
      performed at our hospital to treat allergic rhinitis. However, some patients have
      continous rhinorrhea even though the provocation test after treatment was
      negative. Electrophoretic studies were performed on the nasal discharge of such
      continuous rhinorrhea patients to analyze its protein components, albumin and
      23kD protein. The results showed that the pituita in the unimproved cases with
      negative provocation result was similar in nature to the pituita in vasomotor
      rhinitis patients. It was concluded that the proteins in the pituita were not
      attributable to an antigen-antibody reaction, because the provocation test was
      negative, but they were the result of angiogenic factors (= vasomotor rhinitis).
      Thus it appears that allergic rhinitis can be classified into two types: genuine
      allergic rhinitis and allergic rhinitis associated with vasomotor rhinitis. TCA
      therapy was not effective in the cases of allergic rhinitis with vasomotor
      rhinitis, because they had a pathophysiological feature of vasomotor rhinitis.
      Genuine allergic rhinitis can be differentiated from vasomotor rhinitis
      clinically by measuring albumin and 23kD protein in pituita. It was concluded
      that measurement of 23kD protein concentrations in pituita is effective for
      determining indications for TCA chemotherapy and evaluating its clinical results.

PMID- 7738707
TI  - [Auditory steady-state response to sinusoidally amplitude-modulated tones. Second
      report: investigation of response in the sleeping state].
AB  - The auditory steady state response (SSR) elicited by a sinusoidally amplitude
      modulated (SAM) tone may be an important technique in objective audiometry, which
      provides frequency-specific information. This response is affected the state of
      arousal of the subject. An effect of sleep on the amplitude of this response has
      been observed by a number of previous investigators. Since young children must
      usually be sedated to carry out evoked potential testing, the effects of sleep on
      this response are a crucial factor limiting clinical applicability. The basic
      characteristics of SSR elicited by a 500 Hz SAM tone were studied in 21 adults
      with normal hearing during sleep. The responses while sleeping were compared with
      the responses in the awake state. The responses to 2048 stimuli were averaged
      with the analysis time set at 102.4 ms, and responses were judged by passing the
      waveforms through a 20-100 Hz digital filter. The same technique was performed in
      25 infants (2 months-2 years 9 months) evaluated as having normal hearing. The
      results obtained are summarized as follows: The amplitude of the response while
      sleeping was approximately half the amplitude in the awake state. Responses with
      a modulation frequency of 70Hz, however, showed a persistent decrease in 71.0%,
      suggesting a trend different from that seen at a modulation frequency of less
      than 70Hz. The effect of modulation frequency on response amplitude was almost
      the same for the sleeping state and the awake state. Even during sleep, the
      response amplitude was maximal at modulation frequencies of 20, 30 and 40Hz, and
      there was no significant difference between the values at 20Hz -40Hz. The latency
      of the response was measured by the Diamond method, and the results showed that
      latency is significantly prolonged while sleeping (p < 0.01). The response
      threshold at the 500Hz SAM tone (modulation rate 40Hz, modulation depth 90%) was
      8.5dBnHL when awake and 13.9dBnHL during sleep. The rise in threshold as a result
      of sleep was no more than about 5dB. In infants, the response amplitude at a
      modulation frequency of 20Hz was maximal, and amplitude at the 40Hz was
      significantly smaller (p < 0.01). Latency measured by the Diamond method in
      infants was 12.8ms. Thus, a difference from the response in adults was confirmed.
      Comparisons were made between the responses of infants under 1 year of age and
      infants over 1 year of age to confirm changes in response according to age.

PMID- 7738708
TI  - [The influence of pharyngoplasty on articulation].
AB  - Pharyngoplasty is a surgical technique for the treatment of obstructive sleep
      apnea and snoring. The most commonly employed pharyngoplasty technique is
      uvulopalatopharyngoplasty (UPPP). The anatomical structure of the pharynx is
      usually changed in this procedure, and a change in articulation may result,
      because the pharynx plays a important role in articulation. We, therefore,
      assessed the influence of pharyngoplasty on articulation in patients who
      underwent UPPP. Perceptual study: Twenty-five Japanese monosyllables uttered by
      12 patients were tape-recorded pre-and postoperatively. The results of listening
      tests showed no significant changes in articulation scores for any syllables in
      the pre-and postoperative samples, and there were no nasalized articulations and
      no reduced intensity of consonants. Acoustical study: The first and second
      formant (F1, F2) of the five Japanese vowels pronounced by 20 patients were
      recorded pre-and postoperatively. In addition, intraindividual variation in the
      F1, F2 of the five Japanese vowels were measured in 4 normal subjects. The F1 and
      F2 of the vowel /e/ were slightly higher postoperatively. F2 of vowel /u/ was
      slightly lower postoperatively, and the F2 of vowel /o/ showed the same change.
      These changes in formants, however, fell within the range of intraindividual
      variation. RESULTS: There is no problem in the articulation of phonemes after
      UPPP, but the timbre of the voice may be influenced by the changes in formants.

PMID- 7738709
TI  - [2'-5' olygoadenylate synthetase activity in peripheral facial paralysis].
AB  - Interferons are produced in response to viral infection and play an important
      part in defense by their antiviral effects. An interferon-induced enzyme, 2'-5'
      oligoadenylate synthetase (2-5AS) also takes an important part of the system of
      defense against viral infections, and its activity elevates in nonspecific viral
      infections. This study was designed to evaluate the usefulness of examining serum
      2-5AS activity and peripheral blood WBC 2-5AS (WBC 2-5AS) as diagnostic aids of
      viral infections that cause facial paralysis. Samples were obtained from 83
      patients with Bell's palsy, 20 with Ramsay Hunt syndrome, 74 healthy individuals,
      and a total of 177 subjects. In 177, we measured serum 2-5AS level in 123
      subjects, WBC 2-5AS level in 57, and both in 25. Serum 2-5AS levels in Bell's
      palsy (60 cases) ranged from 20 to 146 pmol/dl (average: 38.5). The range in
      Ramsay Hunt syndrome (13) was 20-333 (average: 59.0), and in healthy controls
      (50), it was 20-128 (average: 41.4). WBC 2-5AS level ranged from 20 to 5900
      pmol/dl (average: 733.2) in Bell's palsy (23 cases), from 20-4540 (average:
      1371.4) in Ramsay Hunt syndrome (7), and from 20-903 (average: 294.5) in healthy
      individuals (24). There were no statistically significant differences in serum 2
      5AS activities. Otherwise, there was significant difference (p < 0.01) between
      healthy individuals and Patients with Ramsay Hunt syndrome in WBC 2-5AS activity.
      In Bell's palsy, 3 cases (13.0%) with markedly high WBC 2-5AS levels
      existed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738710
TI  - Nitric oxide--friend and foe.

PMID- 7738711
TI  - The pathology of cardiac ischaemia: cellular and molecular aspects.

PMID- 7738712
TI  - Accumulation of p53 protein in normal, dysplastic, and neoplastic Barrett's
      oesophagus.
AB  - Accumulation of p53 protein was determined by immunohistochemistry in archival
      material of biopsy specimens from 102 patients with Barrett's oesophagus with
      different grades of dysplasia, in 24 oesophageal adenocarcinomas associated with
      Barrett's oesophagus, and in 23 cases of metaplastic epithelium adjacent to these
      carcinomas. Immunostaining for the p53 protein was found in 23/102 (23 per cent)
      cases of the Barrett's oesophagus biopsies and in 12/23 (52 per cent) cases of
      Barrett's oesophagus adjacent to adenocarcinoma. Significant correlations were
      found between the grade of dysplasia and p53 immunoreactivity in both Barrett's
      biopsies without adenocarcinoma (P < 0.001) and Barrett's oesophagus adjacent to
      adenocarcinoma (P < 0.05). In the adenocarcinomas, intense nuclear
      immunohistochemical staining for p53 was diffusely or focally present in 20/24
      (83 per cent) of the specimens. In Barrett's oesophagus, p53 is a progression
      marker with high expression in high-grade dysplasia (89 per cent) and
      adenocarcinoma (83 per cent).

PMID- 7738713
TI  - p53 expression in normal, dysplastic, and neoplastic laryngeal epithelium.
      Absence of a correlation with prognostic factors.
AB  - p53 expression has been examined in 89 squamous cell carcinomas of the larynx (34
      glottic, 28 supraglottic, 18 transglottic, 8 pyriform sinus, and 1 subglottic)
      obtained from 88 patients surgically treated in our centre. In addition, 59
      laryngeal samples including normal respiratory epithelium and non-invasive
      squamous cell lesions were also tested. Frozen sections were immunostained with
      PAb 1801 and the results were correlated with pathological features, DNA ploidy
      and S-phase of the tumours, disease-free interval, and survival of the patients.
      p53 immunoreactivity was observed in 57 (64 per cent) carcinomas. None of the
      eight samples of normal respiratory epithelium was positive. p53-positive cells
      were seen in 8 of 23 (35 per cent) squamous cell metaplasias, 6 of 19 (32 per
      cent) low-grade dysplasias and 5 of 10 (50 per cent) high-grade dysplasias. No
      correlation was found between p53 expression in carcinomas and their clinical and
      pathological characteristics, DNA ploidy, or proliferative activity. Neither
      disease-free nor overall survival showed differences between p53-positive and p53
      negative cases. These findings indicate that p53 may play a role in an early
      stage of malignant transformation of a subset of squamous cell carcinomas of the
      larynx, but seems not to be associated with further progression of the tumours.

PMID- 7738715
TI  - Loss of heterozygosity in ductal carcinoma in situ of the breast.
AB  - Loss of heterozygosity (LOH) at loci reported to show allele loss in invasive
      breast cancers was examined in ductal in situ carcinomas of the breast using
      polymorphic short tandem repeats and the polymerase chain reaction (PCR). LOH was
      detected at all loci examined in at least 11 per cent of the samples examined.
      The proportion of cases of in situ carcinoma showing LOH at these loci was
      similar to that previously reported in invasive cancers. Cases of pure in situ
      cancer without an invasive component exhibited an overall lower frequency of
      allele loss. LOH at more than one locus was observed in some intraductal cancers.
      In a small number of cases, LOH was present in the invasive but not in the
      intraductal component of the tumour, suggesting that mutation at the locus
      concerned was associated with development of invasive behaviour.

PMID- 7738714
TI  - PCR-mismatch analysis of p53 gene mutation in Hodgkin's disease.
AB  - Expression of the p53 protein can be detected by immunohistochemistry in Reed
      Sternberg (RS) cells, the presumed neoplastic component of Hodgkin's disease (HD)
      lesions. At present, there is no clear molecular evidence that p53 positive
      immunostaining in HD correlates with the presence of mutations or other
      structural alterations of the p53 gene. To address this question, 49 cases of HD
      have been investigated for p53 expression by immunohistochemistry, using the DO1
      monoclonal antibody on paraffin sections. Thirty-seven out of 49 cases (75 per
      cent) exhibited positive immunostaining restricted to RS cells and variants.
      Among these 37 positive cases, ten cases were selected on the basis of a rich
      content of RS cells showing virtually 100 per cent DO1 positivity. A PCR-mismatch
      strategy was chosen for the detection of p53 mutations. The threshold level of
      sensitivity was assessed on positive cell-line controls. A proportion of 10-15
      per cent p53 mutated cells mixed in a normal population could be identified.
      Total genomic DNA was extracted from the ten selected HD cases and PCR
      amplification of exons 5-8 of the p53 gene was performed. Heteroduplex mismatch
      analysis revealed no structural alterations of the p53 gene in any case. In view
      of these findings, it appears unlikely that the sensitivity of the method by
      itself can fully explain the negative results, although this possibility cannot
      be completely ruled out. Thus, it is conceivable that p53 positive immunostaining
      in HD may not necessarily imply genomic alterations in the classic 'hot spot'
      regions and may be related to another mechanism of p53 protein stabilization.

PMID- 7738716
TI  - Expression of c-myc protein is related to cell proliferation and expression of
      growth factor receptors in transitional cell bladder cancer.
AB  - Archival biopsy specimens from transitional cell bladder tumours (n = 185) were
      analysed immunohistochemically for expression of c-myc protein. The results were
      compared with histopathological and clinical parameters and survival. Forty-three
      per cent of the tumours were negative for c-myc protein and weak, moderate, or
      strong cytoplasmic expression was found in 34, 14, and 9 per cent of cases,
      respectively. Nuclear positivity for c-myc protein was detected in 35 per cent of
      tumours and nuclear positivity was related to overexpression of c-erb B-2 (P =
      0.01) and a high proportion of nuclei were also positive for p53 oncoprotein (p <
      0.05). Cytoplasmic expression of c-myc protein was related to histological grade
      (P = 0.005), papillary status (P = 0.007), the S-phase fraction (P = 0.008), the
      mitotic index (P = 0.021), overexpression of epidermal growth factor receptor (P
      = 0.045), and c-erb B-2 (P = 0.17). Expression of c-myc protein was not
      significantly related to the progression of tumours and it had no prognostic
      value in survival analysis. Independent predictors were the T-category (P <
      0.001), papillary status. (P = 0.001), and S-phase fraction (P = 0.061). The
      results show that while c-myc gene product participates in growth regulation of
      human bladder cancer cells, it has no independent prognostic significance.

PMID- 7738717
TI  - MDM2 and CDK4 gene amplification in Ewing's sarcoma.
AB  - Amplification of the MDM2 gene, which maps to chromosome band 12q13 and encodes a
      p53-binding protein, may result in functional inactivation of p53 and has been
      observed in various bone and soft tissue sarcomas. Published studies have
      included few cases of Ewing's sarcoma (ES) or peripheral neuroectodermal tumour
      (PNET), a tumour group in which alterations of the p53 pathway have so far not
      been extensively studied. We examined two ES cell lines, RD-ES and SK-ES-1, and
      30 specimens from 27 patients (24 ES, 6 PNET; 19 primary, 4 local recurrence, 7
      metastasis) for MDM2 gene amplification by Southern blot analysis. All 30
      clinical specimens had been confirmed to contain sufficient ES/PNET DNA by the
      demonstration of a rearrangement of the t(11;22)-associated EWS gene using an EWS
      cDNA probe on the same blots. MDM2 gene amplification was detected in 3 of 30
      specimens (10 per cent), including two ES and one PNET, but in neither of the
      cell lines. The three cases with amplification were morphologically typical
      primary tumours. Two of the three cases also showed co-amplification of the CDK4
      gene, which encodes a cyclin-dependent kinase and also maps to band 12q13.
      Clinically, all three cases had metastatic disease at diagnosis, compared with
      only 1 of 15 MDM2-negative cases where the primary tumour was studied. The
      difference was statistically significant (P = 0.005), suggesting an association
      of MDM2 amplification with advanced stage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738718
TI  - Detection of numerical chromosomal aberrations in paraffin-embedded malignant
      pleural mesothelioma by non-isotopic in situ hybridization.
AB  - An in situ hybridization (ISH) study on paraffin sections of 13 malignant
      mesotheliomas was performed to detect numerical chromosomal aberrations with
      biotin-labelled DNA probes specific for the centromeric regions of chromosomes 1,
      3, 6, 7, 11, and 17. All chromosomes contributed to numerical changes, which can
      be summarized as follows: first, a monosomy for chromosome 6 was found in one
      case; second, in five cases a trisomy for at least one chromosome was detected;
      and third, in seven cases a pentasomy or a higher polysomy was found for at least
      one chromosome. Although these data have to be confirmed on a larger group of
      patients, survival analysis of this group showed no significant difference
      between the first and second groups taken together and the third group. In this
      study no specific numerical chromosomal aberrations were identified.
      Nevertheless, numerical gains appear to be more frequent than has previously been
      shown by karyotype analysis.

PMID- 7738719
TI  - Expression of parathyroid hormone-related peptide in human thyroid tumours.
AB  - The purpose of this study was to evaluate the distribution of parathyroid hormone
      related peptide (PTHrP) in human thyroid tissues. The presence of PTHrP was
      studied immunohistochemically in 107 consecutive patients with human thyroid
      tumours. PTHrP expression was revealed in 97.6 per cent of carcinomas, but not in
      paranodal normal thyroid epithelial cells. Although there were no differences in
      the incidence of PTHrP positivity among papillary, follicular, and anaplastic
      carcinoma cases, PTHrP expression levels were correlated with the growth pattern
      of thyroid cancer. Strong immunopositivity was detected in 67.3 per cent of
      papillary growth tissues in papillary carcinomas. A tissue growth pattern
      consisting of colloid-absent follicles had a high incidence of strong
      immunopositivity irrespective of the histological type of tumour. Anaplastic
      carcinoma without colloid production also showed strong immunoreactivity in all
      cases. In contrast, a growth pattern of colloid-rich follicles did not show
      strong immunopositivity in either papillary or follicular carcinomas. Follicular
      adenomas showed positive immunostaining in only one case, and no adenomatous
      goitres showed PTHrP antigens. In situ hybridization and reverse transcription
      polymerase chain reaction (RT-PCR) revealed strong PTHrP mRNA in thyroid cancer
      tissues, but not in normal thyroid tissues. PTHrP expression was not associated
      with metastasis, calcification, or hypercalcaemia in thyroid cancers. These
      results suggest that the expression of PTHrP in human thyroids is closely related
      to the malignant alteration of normal thyroid epithelial cells, especially in the
      growth pattern of thyroid carcinoma tissues.

PMID- 7738721
TI  - Early increase precedes a depletion of endothelin-1 but not of von Willebrand
      factor in cutaneous microvessels of diabetic patients. A quantitative
      immunohistochemical study.
AB  - Endothelin-1 (ET-1) is a vasoconstrictor peptide which is produced by endothelial
      cells. The subcellular distribution of ET-1 in human skin and the variation of
      immunostaining for ET-1 by light microscopy in skin biopsies of diabetic patients
      have been analysed using immunohistochemistry and image analysis quantification.
      Skin biopsies were collected from 17 patients with type 1 diabetes of different
      durations and with presence or absence of microangiopathy in the retina; skin
      biopsies of healthy subjects were utilized as controls. The distribution of ET-1
      immunoreactivity (IR) at both light and electron microscopy was compared to that
      of von Willebrand factor (vWf), a general marker of total cutaneous microvessels.
      Immunohistochemistry revealed that in controls the distribution of immunostaining
      was similar for ET-1 and vWf, being localized to microvessels in all areas of the
      skin. However, at the electron microscopical level ET-1-IR was localized in the
      endothelial cytoplasm rather than in specific organelles, while vWf
      immunostaining was associated with Weibel-Palade bodies. ET-1-IR was observed in
      4/8 (50 per cent) biopsies from healthy subjects; this increased to 81.8 per cent
      in biopsies of patients affected by diabetes for less than 10 years and decreased
      to 16.6 per cent in patients with diabetes for more than 10 years. Quantification
      of ET-1 staining showed a significant decrease of ET-1-IR in patients affected by
      diabetes for more than 10 years compared with those affected by diabetes for less
      than 10 years (P < 0.05). Also, the percentage of biopsies showing positive ET-1
      staining was lower in patients with retinopathy than in patients without
      retinopathy. On the contrary, vWf-IR was observed in all skin specimens and its
      quantification showed no differences between diabetic patients and controls.
      These changes are not related to variations in the number of blood vessels, and
      it is suggested that they reflect a possible functional alteration of the
      endothelial cells during diabetes.

PMID- 7738720
TI  - Is the carbohydrate sialosyl-Tn a marker for altered, non-malignant activity in
      squamous epithelium in the head and neck region?
AB  - Cell surface carbohydrates are involved in many cell functions such as cellular
      differentiation, adhesion, and invasion. A carbohydrate, sialosyl-Tn (STn), is
      expressed in many human carcinomas but generally not in normal epithelia. In the
      oral mucosa, however, STn has recently been observed on basal cells in some
      lesions with epithelial hyperplasia and dysplasia. The aim of this study was to
      carry out a systematic investigation of STn expression on epithelial basal cells
      in hyperplastic, 'borderline' malignant, and malignant head and neck lesions, to
      see if the expression of STn is associated specifically with hyperplastic
      conditions. Using the primary monoclonal antibody TKH2, normal controls did not
      reveal STn. STn was detected on probably post-mitotic basal cells in hyperplastic
      head and neck lesions and on basal cells adjacent to cancers, but not within the
      carcinomas. A Ki67 antibody reacted with basal cells in other locations. The most
      highly differentiated lesions, such as focal epithelial hyperplasia and verrucous
      hyperplasia, revealed a high percentage (86 per cent in both cases) of STn
      reactivity. The least-differentiated verrucous carcinomas (VCs) and
      keratoacanthomas (KAs) did not express STn, in contrast to the highly
      differentiated VCs and KAs. These findings indicate that STn-negative cases may
      have a greater malignant potential that the STn-positive cases. In conclusion,
      STn expressed on basal cells is possibly a marker for non-malignant conditions
      with altered basal cell activity and for highly differentiated verrucous
      carcinomas.

PMID- 7738723
TI  - Biochemical basis for the killing of Cryptococcus neoformans by rat peritoneal
      cells.
AB  - The biochemical basis of peritoneal cell cytotoxicity for Cryptococcus neoformans
      was studied by measuring the killing of the yeast by peritoneal resident cells
      and peritoneal exudate cells obtained from normal and proteose-peptone-injected
      animals, respectively. Both cell populations killed C. neoformans to an
      equivalent extent after 3 h incubation. Exudate cells showed anti-cryptococcal
      activity from the first hour of incubation, while no killing was observed with
      resident cells before 3 h. Both cell populations triggered a respiratory burst in
      response to opsonized C. neoformans as indicated by the fact that killing of the
      yeast was inhibited by scavengers of reactive oxygen intermediates (ROI). C.
      neoformans susceptibility to H2O2 and hydroxyl radicals in cell-free systems is
      demonstrated by incubating a yeast suspension with different concentrations of
      H2O2 and Fenton's reagents, respectively. These results suggest that oxygen
      metabolites play an active role in C. neoformans killing.

PMID- 7738722
TI  - High prevalence of pancreatic islet amyloid in patients with end-stage renal
      failure on dialysis treatment.
AB  - Islet amyloid polypeptide (IAPP) is the main proteinaceous component of
      pancreatic islet amyloid, which is a characteristic feature of type 2 diabetes.
      The factors responsible for amyloid deposition are unclear. Patients with end
      stage renal failure (ESRF) on dialysis treatment have increased insulin
      resistance which is associated with hypersecretion of beta-cell products.
      Furthermore, elevated concentrations of circulating IAPP are found in these
      patients due to reduced renal clearance of IAPP. To determine the prevalence of
      islet amyloid in this group of patients, pancreas was examined from 23 non
      diabetic [aged 62 (29-79) years, median and range] and four type 2 diabetic [aged
      67 (56-72) years] patients with ESRF on dialysis treatment. Pancreatic specimens
      from 30 non-diabetic control subjects [aged 67.5 (56-86) years] and 14 type 2
      diabetic subjects without renal disease [aged 69 (48-86) years] were used as
      control groups. Islet amyloid was present in all type 2 diabetic patients with
      ESRF and in 12 out of 14 type 2 diabetic control subjects (86 per cent). Amyloid
      deposits were found in 8 out of 23 non-diabetic patients with ESRF (35 per cent),
      which was a higher prevalence than that found in non-diabetic control subjects (3
      per cent) (P < 0.01). This may be related to undiagnosed (pre)diabetes. Elevated
      secretion rates of IAPP due to insulin resistance and high circulating IAPP
      concentrations as a result of severely reduced renal clearance of IAPP will cause
      high pericellular concentrations of IAPP. This condition is likely to enhance
      amyloid fibril formation in pancreatic islets similar to that observed in type 2
      diabetes.

PMID- 7738724
TI  - Detection of Candida casts in experimental renal candidiasis: implications for
      the diagnosis and pathogenesis of upper urinary tract infection.
AB  - The distinction between upper versus lower urinary tract infection in patients
      with candiduria is a commonly encountered and therapeutically important
      diagnostic dilemma. Candida casts have been reported in the urine of several
      individual case reports of human renal candidiasis. The specificity of Candida
      casts would identify unequivocally a patient with upper urinary tract disease.
      Little is known, however, about the sensitivity and the formation of Candida
      casts. We therefore studied the diagnostic yield, methods for detection and
      pathogenesis of Candida cast formation in serially collected urine specimens from
      immunologically intact and granulocytopenic rabbit models of haematogenous
      disseminated candidiasis. Refractile blastoconidia and pseudohyphae of Candida
      encased in the granular matrix were seen on wet mounts while Candida stained a
      brilliant red in the fuschia pink tubular matrix on periodic acid Schiff (PAS)
      stained cytopathology filters. Among 24 rabbits with disseminated candidiasis, 11
      (46%) had Candida casts detectable by wet mount and PAS-stained urine filters in
      comparison to none of 10 non-infected immunologically normal controls (P =
      0.014). Fifteen (70%) of 21 episodes of Candida casts were detected within the
      first 3 days of infection, indicating possible utility in the early diagnosis of
      renal candidiasis. No Candida casts were detected in the urine of
      granulocytopenic rabbits, possibly due to the rapid destruction of tubules and
      abrogation of cast formation. This absence of detectable Candida in eight
      infected granulocytopenic rabbits differed significantly from that of 24 non
      granulocytopenic infected rabbits, in which Candida casts were detected in 11
      (46%) (P = 0.029). Candida cast formation occurred predominantly in the cortex.
      Histopathological examination demonstrated invasion of Candida into the
      glomerular tufts and peritubular capillaries, followed by development of Candida
      casts in the proximal and distal tubules, respectively. Detection of renal
      Candida casts may be a useful diagnostic marker in distinguishing upper versus
      lower urinary tract candidiasis.

PMID- 7738725
TI  - Purification and characterization of an extracellular aspartic proteinase from
      Aspergillus fumigatus.
AB  - An aspartic proteinase (PEP) from the culture supernatant of a clinical isolate
      of Aspergillus fumigatus was purified to virtual homogeneity at a yield of 24%.
      The procedure involved affinity chromatography on pepstatin agarose, the
      interaction requiring a chaotropic salt (sodium trifluoroacetate) for complete
      elution of the enzyme. Among 11 amino acids of the N-terminal region, nine were
      identical with the corresponding sequence of the aspartic proteinase
      aspergillopepsin A from Aspergillus niger var. awamori (previously called
      Aspergillus awamori). Thus PEP belongs to the aspergillopepsins, a family of
      closely related aspartic proteinases produced by aspergilli. Specific antibodies
      against PEP were detected by dot blot assay in sera of two patients with
      aspergillosis. In addition, PEP antigen was demonstrated by immunofluorescence in
      mycotic human lung, using specifically elicited antibodies from guinea-pigs. PEP
      had an estimated molecular mass of 38 kDa and the pI was determined at pH 4.2.
      PEP is therefore likely to be closely related to an acid proteinase of A.
      fumigatus which was originally described in 1981.

PMID- 7738727
TI  - Differential release of an immunodominant 65 kDa mannoprotein antigen from yeast
      and mycelial forms of Candida albicans.
AB  - The release of mannoprotein (MP) antigen from Candida albicans grown at 28
      degrees C (yeast form) or 37 degrees C (mycelial form), and the ability of each
      released material to stimulate a cell-mediated immune (CMI) response by human
      lymphocytes in vitro, were studied. Overall, the mycelial cells released more MP
      per unit of dry mass increase and the released material was relatively enriched
      with MP constituents of lower molecular mass with respect to the material
      released from yeast cells. Moreover, the mycelial MP contained a 65 kDa component
      (MP65) which was the largely predominant MP recognized by a rabbit anti-mycelium
      antiserum. When peripheral blood mononuclear cells from normal human subjects
      were stimulated in vitro with graded amounts of yeast or mycelial MP, the latter
      was about one order of magnitude more potent than the former in inducing
      lymphocyte proliferation. Following MP separation by gel permeation
      chromatography, an appreciable CMI response was stimulated only by the MP65
      containing MP fractions, and to a degree apparently related to the amount of MP65
      itself. Altogether, these data confirm our previous findings about the MP65
      antigen as a major target of CMI response to C. albicans, and demonstrate that
      this antigen is released predominantly by the mycelial cells of the fungus in
      vitro.

PMID- 7738726
TI  - Helical growth of hyphae of Candida albicans.
AB  - When grown on a range of surfaces in conditions favouring hyphal growth, hyphae
      of Candida albicans grew in a right-handed helical fashion. This phenomenon was
      observed with eight strains and with two nutrient media. It is suggested that
      this is a result of rotation of the hyphal apex as it extends, which on some
      surfaces results in a helical hyphal wall, but which in a liquid results in a
      straight hypha. The consequence is that on a surface, a helically growing hypha
      will be exposed to a more diverse environment than a straight hypha. This
      phenomenon may have significance in the colonization of tissue by C. albicans.

PMID- 7738728
TI  - The relationship between the glucose uptake system and growth cessation in
      Candida albicans.
AB  - It is thought that dimorphic Candida albicans undergoes changes in its
      intracellular metabolic state prior to yeast-mycelial transformation. Cells grown
      in budding form to mid-exponential phase could not be induced to form germ tubes
      when grown in glucose medium. However, cells in which growth was initially
      inhibited by either starvation or inhibitors (0.1% hydroxyurea, 4% sodium
      malonate or 4% 2-deoxy-D-glucose) could be induced to form germ tubes in the same
      medium. The effects of these initial treatments on the intracellular state in mid
      exponential phase cells were analysed by measuring the kinetics of D-glucose
      uptake. D-glucose uptake in mid-exponential phase and stationary phase cells was
      measured. The untreated mid-exponential phase cells exhibited only a high Km (6.9
      mM). However, mid-exponential phase cells, in which growth was initially
      inhibited, exhibited both a high Km (3.2-6.2 mM) and a low Km (0.40-0.78 mM)
      simultaneously. In addition, the stationary phase cells exhibited both a high Km
      (5.6 mM) and a low Km (0.56 mM). These results suggest that there are two
      kinetically distinct systems of glucose transport in C. albicans and that changes
      in the glucose uptake system in C. albicans may be related to intracellular
      changes prior to transition from the budding to the mycelial form.

PMID- 7738729
TI  - Efficacy of AmBisome in murine coccidioidomycosis.
AB  - ICR mice were infected intranasally with arthroconidia of Coccicioides immitis.
      Mice were treated intravenously with amphotericin B deoxycholate (Fungizone) or
      an amphotericin B-lipid vehicle (AmBisome). Doses ranged from 0.05 to 1.0 mg kg
      1. Lung weight, which parallels disease severity and fungal burden in this
      infection, was used as the index of protection. Both Fungizone and AmBisome were
      significantly and equally protective at 0.3 and 1.0 mg kg-1 body weight.

PMID- 7738730
TI  - Scanning electron microscope observation of adherence of Candida albicans to
      cultured keratinocytes.
AB  - The role of antigen 6 in the adherence process of Candida albicans serotype A to
      cultured keratinocytes was examined with a scanning electron microscope. The
      number of adhered organisms was significantly lower for the antigen 6-deficient
      mutant strain than for the antigen 6-positive parent strain (P < 0.001). Fibril-
      or strand-like structures bridging the organisms and the keratinocytes were found
      to develop during the later stages of adherence.

PMID- 7738731
TI  - "Matchmaker-matchmaker"--the evolution of pediatric surgical training programs
      and the selection of candidates for pediatric surgical training through the first
      quarter-century of the American Pediatric Surgical Association.

PMID- 7738732
TI  - Lessons learned in the management of hemolytic uremic syndrome in children.
AB  - Escherichia coli O.157:H7 is a serious and common human pathogen that can cause
      diarrhea, hemorrhagic colitis, and the hemolytic uremic syndrome (HUS). During a
      massive outbreak of infection with E coli O157:H7 in January 1993 in Washington
      State, more than 600 people, mostly children, acquired symptomatic infection, and
      37 were hospitalized with HUS at Children's Hospital and Medical Center in
      Seattle, and six at other hospitals in Washington. Twenty-one (57%) required
      dialysis. Nineteen (51%) had significant extrarenal pathology: gastrointestinal
      in 14 patients (38%), cardiovascular in 13 (35%), pulmonary in 9 (24%), and
      neurological in 6 (16%). Most patients were managed nonoperatively, but three
      required total abdominal colectomy and one a left colectomy. No child had
      perforation. Three patients died, all of whom had multisystem disease. The
      authors recommend (1) that all patients with bloody diarrhea undergo
      microbiological evaluation for E coli O157:H7 before any surgical intervention;
      (2) avoidance of antibiotics and antimotility agents in patients with proven or
      suspected infection with E coli O157:H7 until the safety and efficacy of such
      interventions have been established in controlled trials; (3) that patients with
      E coli O157:H7 infections be evaluated for microangiopathic changes consistent
      with HUS in the week after onset of diarrhea; (4) nasogastric suction for severe
      symptoms, and frequent abdominal evaluations, tests (electrolytes/amylase), and
      roentgenograms to exclude treatable abdominal disorders; and (5) institution of
      hemodialysis for oliguria/anuria, acidosis, or rising creatinine. The authors
      recommend surgical exploration for toxic megacolon, colonic perforation, acidosis
      unresponsive to dialysis, or recurrent signs of obstruction or colonic stricture.

PMID- 7738733
TI  - Midaortic syndrome and hypertension in childhood.
AB  - Midaortic syndrome is a form of fibromuscular hyperplasia that involves the
      abdominal aorta including the renal and visceral branches. Symptomatology depends
      on the degree and location of vessel narrowing. This report updates the authors'
      experience and details 17 operative cases, the largest reported series. Seventeen
      of the 45 patients who have been operated on for severe renovascular hypertension
      have had this syndrome. Ages have ranged from 5 months to 15 years (average, 9.7
      years). Signs and symptoms have included various manifestations of malignant
      hypertension, congestive heart failure, oliguric renal failure, and claudication.
      Intestinal angina has not been noted despite celiac and/or superior mesenteric
      arterial involvement. Although balloon angioplasty was performed in two patients,
      lasting results were not achieved. One primary nephrectomy was performed. The
      other 16 patients had vascular reconstructions including aortoaortic bypass
      grafting (n = 12), with bilateral renal artery bypasses (n = 9) or unilateral
      renal bypass (n = 3) or bilateral renal bypass alone (n = 4). The majority had
      associated visceral artery narrowing, but excellent collaterals have been present
      so no visceral reconstructions have been required. All renal artery bypasses have
      been with reinforced saphenous vein. RESULTS: In the average follow-up period of
      48 months, 12 of the 17 patients have been cured of hypertension, and the other
      five have improved. Claudication, congestive failure, and renal failure have been
      alleviated. Thus far, reinforcement of the saphenous vein grafts has prevented
      aneurysmal degeneration and graft loss. CONCLUSION: These results indicate that
      aggressive single-stage reconstruction is the best approach for these children.

PMID- 7738734
TI  - Pediatric appendectomy.
AB  - PURPOSE: To define patterns of care and outcome for pediatric appendectomy.
      METHODS: A study was designed to evaluate all pediatric appendectomies performed
      in the 147 Department of Defense hospitals worldwide. Cases of nonincidental
      appendectomy were identified through discharge diagnoses and operative logs, and
      98.6% of the charts were retrieved for review. All charts were abstracted, and
      data were entered into a 127-field database for analysis. RESULTS: Over a 12
      month period, ending January 1993, appendectomy was performed on 1,366 pediatric
      patients in the Department of Defense hospital system. The patients' median age
      was 12 years (range, 6 months to 18 years); 59% were male. The diagnosis was
      normal appendix for 157 patients (12%), acute nonperforated appendicitis for 930
      (68%), and perforated appendicitis for 279 (20%). Age < or = 8 years was
      predictive (P < .001) of a higher rate of perforated appendicitis (33% v 18%) but
      was not predictive of normal pathology (13% v 11%). Female gender was associated
      with a significantly higher rate of normal pathology (17% v 8%; P < .001) but not
      of perforation (18% v 22%). Temperature elevation and right lower quadrant pain
      and tenderness did not clinically distinguish between diagnostic groups. Sixty
      two percent of patients with a normal appendix had a white blood cell count of
      more than 10,000/mm3, as did 91% of patients with acute or perforated
      appendicitis. Those with perforated appendicitis received pre- and postoperative
      antibiotics, primarily ampicillin/gentamicin/clindamycin or Flagyl (41%),
      cefoxitin (34%), or Unasyn (15%). In 77% of this subgroup, intraoperative
      cultures were positive, with isolates for Escherichia coli (76%) Enterococcus
      (30%), Bacteroides (24%), and Pseudomonas (20%) predominating. There were no
      deaths. Major complications occurred in 1.2% of patients with acute appendicitis
      and in 6.4% of those with perforated appendicitis; there were no major
      complications in the group with normal appendectomies. The hospitalization period
      was more than 7 days for 1.6%, 40%, and 3.8%, respectively. CONCLUSION: This
      large series, from a large number of hospitals, with multiple practitioners, can
      serve as a community standard for pediatric appendectomy in the 1990s.

PMID- 7738735
TI  - Diagnosis and treatment of symptomatic breast masses in the pediatric population.
AB  - Between 1980 and 1993, 74 children and adolescents were referred for surgical
      evaluation of palpable breast masses. Thirty-two were managed nonoperatively for
      unilateral thelarche (26), fibroadenoma (3), gynecomastia (2), or hemorrhagic
      cyst (1). The other 42 children had surgical intervention for giant or painful
      fibroadenomas (19), breast abscesses (5), painful gynecomastia (6), metastatic
      disease (4), or other conditions (8). No instances of primary breast malignancy
      were noted. Physical examination and minimal (selective) diagnostic testing can
      conserve health care dollars in cases of pediatric patients with breast masses.

PMID- 7738736
TI  - Sclerotherapy for venous malformations.
AB  - Of the congenital vascular abnormalities, venous malformations receive little
      attention and essentially no discussion of treatment. The author describes a 30
      year experience with sclerotherapy, which was used for 34 venous malformations.
      In some cases, these lesions are localized and can be excised, but all the
      patients in this series had such extensive involvement of adjacent organ systems
      that no other treatment than sclerotherapy was tenable. Five patients had Klippel
      Trenaunay Syndrome, five had head and neck involvement, two had involvement of
      the entire left side and the remainder had other areas affected. Sodium
      morrhuate, ethanolamine, sotradecol, and absolute ethyl alcohol were the
      sclerosing agents used. A butterfly needle was inserted into an anomalous vein,
      and a three-way stopcock connected to saline and the sclerosing solution was used
      to ensure intraluminal injection. When rapid runoff into normal venous
      tributaries could be a concern, a venogram on the operating table preceded
      injection of the sclerosing solution. Small lesions required only one treatment;
      widespread bulky lesions required more than 30 injections. The volume of
      sclerosing solution varied from 5 to 90 mL per injection course. Because of pain,
      general anesthesia and an overnight hospital stay were necessary. Patients with
      pharyngeal and/or laryngeal involvement required preliminary tracheostomy or
      endotracheal ventilatory support for 3 days. Complications included skin
      necrosis, transient nerve palsy, hemoglobinuria, and one case of anaphylaxis.
      Repeated aggressive treatment was required for the very large malformations
      because recanalization occurred. All the patients have been very satisfied with
      the results.

PMID- 7738737
TI  - Stapled intestinal anastomosis in neonates and infants: use of the endoscopic
      intestinal stapler.
AB  - Stapled anastomoses of the gastrointestinal tract, commonplace in adults and
      older children, are rarely performed in newborns because of the size of the
      instruments. The development of smaller stapling devices for laparoscopic and
      thoracoscopic procedures presented an opportunity to evaluate the efficacy of
      such anastomoses in neonates and infants. Over an 11-month period, seven newborn
      or young infants underwent stapled functional end-to-end small or large
      intestinal anastomoses using the Endo-GIA 30. The male:female ratio was 3:4, and
      the mean age was 72d (range, 1 to 134 days). The mean weight at the time of the
      stapled anastomosis was 3.7 kg (range, 1.88 to 6.6 kg). The clinical setting
      requiring the intestinal anastomoses included ileostomy closure after perforated
      necrotizing enterocolitis (3), intestinal atresia (1), distal ileal volvulus (1),
      left colon mesenteric cyst (1), and biliary atresia (1). There were no deaths or
      anastomotic leaks. Nasogastric decompression was discontinued at a mean of 6 days
      (range, 3 to 11 days), and oral feedings were begun at a mean of 7.0 days (range,
      4 to 12 days). The patients were discharged from the hospital 7 to 117 days after
      the operation (mean, 33 days). The endoscopic stapling instrument is safe and
      effective in performing small and large intestinal anastomoses in newborns and
      young infants.

PMID- 7738738
TI  - A model of scarless human fetal wound repair is deficient in transforming growth
      factor beta.
AB  - Human fetal skin heals via scarless regeneration, whereas adult skin heals with
      scar. Scarless repair may reflect a distinct cytokine milieu. We studied the role
      of the cytokine transforming growth factor beta (TGF beta) using an established
      model of scarless human fetal skin repair in which human fetal skin is
      transplanted into a subcutaneous pocket on the flank of an adult nude mouse. In
      this model, wounded 16-week-gestation human fetal skin heals without scar,
      whereas wounded adult skin heals with scar. Seven days after transplantation,
      incisional wounds were made in the skin grafts. In the first phase of the study,
      wounds were harvested from 1 hour to 4 weeks postwounding, and
      immunohistochemistry was performed for TGF beta (isoform nonspecific), TGF beta
      1, and TGF beta 2. Scarfree wounds in the fetal skin grafts did not show TGF beta
      staining. In contrast, wounds in adult grafts that heal with scar demonstrated
      isoform nonspecific TGF beta staining from 6 hours through 21 days, TGF beta 1
      from 6 hours through 21 days, and TGF beta 2 from 12 hours through 7 days. In the
      second phase of the study, a slow-release disk with 0.01, 0.1, 1.0, or 10
      micrograms of TGF beta 1 was placed beneath the fetal skin graft at the time of
      wounding. Fourteen days postwounding, there was marked scarring in the fetal
      grafts treated with TGF beta 1, and the size of the scar was proportional to the
      amount of TGF beta 1 applied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738740
TI  - The efficacy of laparoscopic examination of the internal inguinal ring in
      children.
AB  - The ability of physicians to identify a patent processus vaginalis by
      laparoscopic examination of the internal ring is now well established, but the
      efficacy on patient outcome is not. The authors reviewed their experience to
      determine the effect of diagnostic laparoscopy of the internal ring on the
      management of children with inguinal hernias. The records of 150 children who
      underwent inguinal surgery were reviewed--75 before (group 1) and 75 after (group
      2) pediatric laparoscopy was introduced into the authors' practice. The children
      in group 1 were selected for unilateral or bilateral surgery based on history,
      age, sex, side of presentation, and parental preference. For group 2, laparoscopy
      was an additional option offered to appropriate patients. Laparoscopy was
      performed in 43 group 2 patients, using an infraumbilical site. The minimum
      follow-up period was 2 years for group 1 and 1 year for group 2. The mean ages
      for groups 1 and 2 were 41.2 and 39.7 months, respectively. There were 61 boys
      and 14 girls in each group. The percentages of right (R), left (L), and bilateral
      (B) findings, based on clinical observation, were 56.0 (R), 29.3 (L), and 14.7
      (B) for group 1, and 58.7 (R), 26.6 (L), and 14.7 (B) for group 2. The incidence
      of bilateral surgical exploration was similar for the two groups (group 1, 58.6%;
      group 2, 61.3%). The addition of laparoscopy significantly lowered the incidence
      of negative explorations (group 1, 16.0%; group 2, 2.6%; P < .01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7738741
TI  - Primary button gastrostomy: a simplified percutaneous, open, laparoscopy-guided
      technique.
AB  - PURPOSE: Button gastrostomy (BG) insertion has been a secondary procedure after
      initial open Stamm or percutaneous endoscopic tube gastrostomy. Previous attempts
      at primary open BG have been limited by the difficulty in bringing the BG "wings"
      through the abdominal wall. We employed an innovative technique for primary BG,
      which eliminates many of the disadvantages inherent in tube gastrostomy. METHODS:
      From June 1993 to April 1994, primary BG insertion was performed in 34 children,
      using a silicon BG in a tapered peel-away sheath. Seventeen children had
      percutaneous endoscopic insertion of the BG. Six (35%) weighed less than 10 kg.
      Simultaneous laparoscopic guidance was used for percutaneous BG insertion in two
      children who had had multiple previous abdominal procedures. Open BG was
      performed during concomitant abdominal procedures in 15 patients and after
      unsuccessful percutaneous BG in two patients. Twelve patients (71%) weighed less
      than 10 kg. The standard Stamm technique was used for open BG insertion, and the
      tapered peel-away sheath was readily brought out through a remote incision in the
      abdominal wall. RESULTS: The mean operative time for percutaneous primary BG was
      12 minutes from needle insertion (range, 10 to 22 minutes). The mean time until
      BG feeding was 18 hours after insertion (range, 12 to 48 hours). No serious
      complications occurred in any of the 34 patients. Follow-up (1 to 10 months) has
      shown minor tissue reaction, minor leakage, and enthusiastic patient and parent
      satisfaction. CONCLUSION: This innovative technique has proven safe and effective
      and allows for insertion of a skin-level, nonrefluxing, nonreactive, self
      retaining feeding device, which eliminates the need for initial open or
      percutaneous tube gastrostomy and the associated complications. Potential cost
      savings may result through elimination of secondary button insertion procedures
      and the radiological studies often used to confirm proper button placement.

PMID- 7738739
TI  - Update on the analysis of the need for pediatric surgeons in the United States.
AB  - Accurate estimations of pediatric surgical manpower needs are necessary if this
      specialty is to avoid the consequences of under- or oversupply, and reasonable
      decisions must be made relative to the number of training programs needed.
      METHODS: Fifteen, 10, and 5 years ago, pediatric surgeons (PSs) in 62 standard
      metropolitan statistical areas (SMSAs) having a population of at least 200,000
      were asked to estimate the number of PSs needed in their localities. A computer
      program analogous to the SOSSUS program was designed to project the number of PSs
      that would result from various numbers of trainee graduates per year. The program
      has been updated for comparison. Known input data included the present number and
      age of PSs, age range of trainees, current US population projections to the year
      2025, and the average retirement age. RESULTS: These PSs estimated that 88
      additional PSs are needed in the next 10 years. Currently, 26 programs in the
      United States graduate an average of 24 trainees per year, and six programs in
      Canada graduate six trainees per year. The previous projection indicated that 20
      trainees per year would result in 525 PSs in 1993, and the actual number is 559;
      so the figures indicate that 27 or 28 PSs are entering practice each year. The
      apparent increase in numbers is related to entry of Canadian trainees primarily,
      and a few others, into practice. The current computer projection indicates that
      20 graduate trainees per year would result in an absolute increase of 0.55% per
      year, and 25 per year would result in an increase of 1.43% per year, to 2020,
      while the increases in the US population would be 1.02% per year for all ages and
      0.52% for 0 to 15 year olds. If all programs currently being considered for
      approval are certified, as many as 36 trainees per year--or 7 times the rate of
      the 0-15-year population increase--will result. CONCLUSION: Although an average
      of 20 graduates per year entering practice would keep pace with the pediatric
      population, 25 to 27 graduates per year--or 3.5 to 4 times the rate of the 0- to
      15-year population increase--can be accommodated now into the current system of
      delivery of pediatric surgical care on the basis of estimated need. Many more
      graduates than this would create an excess of surgeons before long.

PMID- 7738743
TI  - Cost per anomaly: what does a diaphragmatic hernia cost?
AB  - The cost of medical care in the United States is under close scrutiny. Birth
      defects have surpassed prematurity as the leading cause of infant mortality in
      the United States and contribute significantly to infant morbidity. Few estimates
      have been made of the costs of individual birth defects. The authors sought to
      determine the cost of initial hospitalization for an infant with a congenital
      diaphragmatic hernia (CDH). They analyzed hospital bills and professional fees
      from all 35 cases of infants who underwent postnatal CDH repair at their
      institution between January 1990 and December 1993. The cost averaged $137,000
      per patient, and ECMO dramatically increased the cost. The cost per survivor was
      $98,000 in the non-ECMO group and $365,000 in the ECMO group. The estimated cost
      of CDH per year in the United States is more than $230 million. This study
      suggests several strategies for cost reduction, provides data for future cost
      comparisons, and serves as a cost comparison for evaluating new therapeutic
      strategies for CDH.

PMID- 7738742
TI  - Management of pediatric blunt splenic injury: comparison of pediatric and adult
      trauma surgeons.
AB  - The majority of injured children requiring hospitalization in the United States
      are cared for by nonpediatric surgeons. To determine whether there are
      differences in the management strategies (frequency of operative intervention) of
      pediatric and nonpediatric surgeons caring for children with blunt splenic
      injury, the data for children with this injury from the entire state of Vermont
      and the National Pediatric Trauma Registry were compared. From January 1, 1985
      through December 31, 1991, 817 children (aged < 19 years) were entered into the
      study. There was operative intervention for splenic injury in 21% of the children
      managed by pediatric surgeons and in 52% of those managed by "adult" trauma
      surgeons (P < .05). This significance was maintained when operative rates were
      analyzed with control for injury severity score and age. The overall splenectomy
      rate was higher among cases treated by nonpediatric surgeons (24% v 13%; P <
      .05). In addition, previously reported factors (transfusion requirements, length
      of stay, hospital costs) used by opponents to nonoperative management were
      studied to determine management influence. Both transfusion requirement and
      hospital cost were lower for patients managed nonoperatively (P < .05). Length of
      hospital stay did not differ between the groups. Acute mortality rates were
      similar. The management of children with splenic injury must take into
      consideration the long-term morbidity associated with splenectomy as well as the
      acute operative morbidity. Today, adult trauma surgeons appear to manage children
      with blunt splenic injury with practice standards more appropriate for adult
      patients. Outcome analysis must include methods of care and their long- and short
      term consequences to be considered valid.

PMID- 7738744
TI  - The protective role of enteral IgA supplementation in neonatal gut origin sepsis.
AB  - Preterm infants and infants unable to breast feed are particularly susceptible to
      gut origin sepsis. Many studies have shown the benefits of breast milk in
      decreasing the incidence of bacterial infections in neonates. Little in vivo work
      has focused on prevention of neonatal gut origin sepsis with breast milk
      components. The aim of this study was to determine whether supplementation of a
      standard neonatal formula with exogenous, luminally administered, human secretory
      IgA protects against gut origin sepsis in a newborn rabbit model. Sixty New
      Zealand white rabbit pups were delivered by cesarean section 1 day preterm and
      divided into two groups--the IgA group (n = 26) and the non-IgA group (n = 34).
      Animals were gavage-fed a standard artificial formula (KMR) twice daily. The IgA
      group was supplemented on days 3 and 4 with 6.25 mg/kg of human secretory IgA.
      The non-IgA group received an equal volume of saline. On the evening of day 3,
      the animals were orally challenged with Escherichia coli K100. The quantity of
      bacteria that colonized the cecum was similar in the two groups. The quantity of
      bacteria that translocated to the mesenteric lymph node, liver, and spleen was
      significantly lower in the IgA group (P < .05). The incidence of translocation to
      the organs was also significantly lower in the IgA group (P < .05). The exogenous
      secretory IgA showed specificity to E coli K100 by ELISA. These data show that
      neonatal formula supplemented with human secretory IgA decreases the incidence
      and quantity of bacterial translocation of E coli K100 in a neonatal rabbit
      model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738745
TI  - The effect of cholecystokinin-octapeptide on the hepatobiliary dysfunction caused
      by total parenteral nutrition.
AB  - PURPOSE: Patients on total parenteral nutrition (TPN) commonly have hepatobiliary
      dysfunction. Interruption of the enterohepatic circulation (EHC) and gallbladder
      stasis are part of the pathogenesis. Cholecystokinin-octapeptide (CCK-OP), by
      emptying the gallbladder, stimulates the EHC. This study was performed to
      determine whether daily CCK-OP infusions can ameliorate the hepatobiliary
      dysfunction caused by TPN. METHODS: Rabbits maintained on a standard TPN for 12
      days were divided into two groups. One group (n = 6) received daily intravenous
      doses of CCK-OP, and the other (n = 13) received TPN only. A lab-chow-fed (LCF)
      group (n = 8) served as controls. The authors studied bile flow and bile acid
      secretion rates, sulfobromophthalein (BSP) secretion, gallbladder emptying in
      response to CCK-OP, and liver histology. RESULTS: The LCF group had a bile flow
      of 82.3 microL/kg/min; that for the TPN-only group was 45.7 microL/kg/min (P <
      .001). The daily CCK-OP group did not improve more than the TPN-only group, with
      a bile flow of 45.8 microL/kg/min (P = NS). Bile acid secretion was 0.64
      mumol/kg/min for the LCF group, 0.46 for the TPN-only group (P = NS), and 0.46
      for the daily CCK-OP group (P = NS). TPN impaired the ability of the gallbladder
      to empty, and this was restored with daily CCK-OP. In the LCF group, the mean BSP
      secretion was 81.7% of a 5-mg/kg bolus within 60 minutes, compared with 72.5% in
      the daily CCK-OP group (P = NS) and 63.5% in the TPN-only group (P < .01).
      Histological examination of the liver showed that daily CCK-OP produced less
      periportal inflammation and fibrosis, although all TPN groups had hepatocyte
      damage in the centrilobular area. CONCLUSION: Stimulation of the EHC with daily
      CCK-OP infusions during TPN decreased periportal inflammation and fibrosis,
      maintained gallbladder emptying capacity, and improved organic anion (BSP)
      secretion, although bile flow and bile acid secretion were not improved, and
      hepatocyte damage persisted.

PMID- 7738746
TI  - Intraoperative evaluation of extent of aganglionosis by a rapid
      acetylcholinesterase histochemical technique.
AB  - Using a supplemental oxidation step, the authors modified the
      acetylcholinesterase (AChE) histochemistry technique of Karnovsky and Roots to
      produce staining of cholinergic nerve fibers in 10 minutes rather than in 2
      hours, as required with the conventional AChE technique. They examined
      seromuscular intestinal biopsy specimens taken at three levels (aganglionic,
      transitional zone, ganglionic) from 10 patients during pull-through operations
      for Hirschsprung's disease, using the rapid AChE technique in addition to H&E
      staining. Using the acetylcholinesterase technique, the hypertrophic nerve trunks
      in the aganglionic segment and ganglion cells in the ganglionic segment stained
      strongly and were easily noticeable. The authors believe that the rapid AChE
      technique is a simple and reliable method for intraoperative evaluation of the
      extent of the aganglionic segment, because it provides quicker and more accurate
      identification of ganglion cells and hypertrophic nerve trunks in the space
      between the longitudinal and circular muscle layers of the bowel wall.

PMID- 7738747
TI  - Intestinal neuronal dysplasia is a possible cause of persistent bowel symptoms
      after pull-through operation for Hirschsprung's disease.
AB  - The proximal margin of the resected bowel specimens from 33 consecutively treated
      patients undergoing a definitive pull-through operation for Hirschsprung's
      disease (HD) and control specimens consisting of suction rectal biopsy specimens
      obtained from 24 age-matched patients evaluated for constipation (and proven not
      to have HD) were examined using conventional H&E staining and
      acetylcholinesterase (AChE) histochemistry. Complete resection of the aganglionic
      segment was confirmed in 31 patients. In one patient, the proximal margin was
      found to be aganglionic; in another, the proximal margin was in a transitional
      zone. In both patients, frozen sections at the time of surgery were interpreted
      as having ganglion cells. In 10 of 31 patients, intestinal neuronal dysplasia was
      demonstrated in the proximal margin of the resected bowel. The abnormalities
      included hyperplasia of the submucous plexus, giant ganglia (with > 7 ganglion
      cells), and ectopic ganglion cells (all 10 patients) and increased AChE activity
      in the lamina propria (5 patients). All ten patients with IND had persistent
      bowel problems after the definitive operation for HD, such as enterocolitis,
      soiling, or constipation. Only four of the other 21 patients had persistent bowel
      symptoms. This study suggests that IND is commonly associated with HD. It also
      emphasizes the importance of histochemical examination of the resected segment to
      predict postoperative bowel function in patients with HD.

PMID- 7738748
TI  - Quantitative analysis of neuronal innervation in the aganglionic bowel of
      patients with Hirschsprung's disease.
AB  - Although there is marked proliferation of nerve fibers in the aganglionic bowel
      of patients with Hirschsprung's disease (HD), controversy exists as to whether
      these fibers terminate in the cells of the bowel wall. This study quantitates
      biochemically the synaptic vesicle proteins and neurofilaments in the aganglionic
      bowel of HD patients. The bowel specimens obtained from 12 patients with HD (mean
      age, 4.6 months) and nine age-matched controls were analyzed by Western blot
      analysis using monoclonal antibody 171B5 against the synaptic vesicle 38,000-d
      protein (SVP38), and the specific band obtained was quantitated by densitometry.
      Similarly, using monoclonal antibody NF70K for detecting the 70,000-d component
      of neurofilament (NF70), nerve fibers were quantitated. In the aganglionic HD
      bowel, the quantity of SVP38, representing a proportion of synapses, was
      significantly lower than that in the normoganglionic bowel (P < .001). The
      quantity of NF70, representing a proportion of nerve fibers, was significantly
      greater than that in the normoganglionic bowel (P < .05). These findings suggest
      that the nerve fibers in the aganglionic bowel of HD patients have much less
      developed connections with the cells of the bowel wall, indicating overall poor
      innervation, despite marked proliferation of the nerve fibers.

PMID- 7738750
TI  - A proposed classification of vaginal anomalies and their surgical correction.
AB  - A classification of vaginal anomalies has been derived, which permits logical
      operative decisions. This tool allows the assignment of increasingly involved
      reconstructive operations to progressively more complex vaginal anatomies. The
      outcome of this approach in 49 vaginal reconstructions performed in 36 patients
      over a 25-year period has been analyzed. The cause was found to be congenital
      adrenal hyperplasia in 21 patients, gonadal dysgenesis in four, and cloaca in
      two; nine children had other causes. Based on the following anatomic
      classification and the authors' clinical experience, the following approaches to
      reconstruction can be recommended. Eight infants with labial fusion (type I)
      underwent simple introitoplasty. Fourteen patients with distal urogenital sinus
      (type II) underwent flap vaginoplasty using labioscrotal tissue and/or a
      posteriorly based flap. Pull-through vaginoplasty was used in 10 children with
      distal vaginal atresia and proximal urethrovaginal fistula (type III). Four
      patients with absence of the vagina (type IV) required segmental colon
      vaginoplasty. Thirteen revisions have been required in nine patients thus far.
      The follow-up period is 1 to 17 years, and despite the need for reoperation, all
      but two patients have excellent or satisfactory results based on anatomic and
      functional considerations. The choice for and timing of vaginal reconstruction
      rests on precise anatomic evaluation. The complexity of vaginal reconstruction in
      the growing child and the essentiality of psychosocial adjustment to appropriate
      sexual identity and function mandate long-term comprehensive follow-up. Optimal
      care for each patient requires experience and continuity to take the child
      through diagnosis, surgical reconstruction, stressful adolescence, and into
      adulthood with full attention to anatomic, physiological, and psychological
      support.

PMID- 7738749
TI  - Left ventricular failure complicating severe pediatric burn injuries.
AB  - PURPOSE: Despite improvements in the overall survival rates for critically burned
      children, failed resuscitation may account for 54% of deaths following burn
      injuries. Clinical and experimental studies have implicated failure of the right
      side of the heart in adults, biventricular failure in elderly patients, and
      inadequate resuscitation as causes of refractory burn shock. This retrospective
      study of resuscitation at a tertiary pediatric burn center showed that myocardial
      depression is a complicating factor in the treatment of the pediatric burn
      victim. METHODS: From 1989 to 1992, 28 critically burned children (> or = 60%
      total burn surface area) were resuscitated primarily at our center (admission
      within 24 hours of injury). Twenty-seven children had central lines, nine of whom
      underwent pulmonary artery catheterization for intensive hemodynamic monitoring
      because standard resuscitative therapy had failed. The average amount of fluid
      received at 8 and 24 hours after injury was within 10% of the calculated volume
      based on the Parkland formula. RESULTS: Indexes of a failing rescue attempt
      included respiratory distress (PaO2/FlO2 < or = 200), central venous pressure of
      greater than 10 mm Hg, and urine output of less than 1 mL/kg/h. Filling pressures
      were found to be normal or elevated in all children, indicating adequate volume
      replacement. Evaluation of cardiac function was performed using a thermodilution
      technique and showed that 100% of the study group had depressed left ventricular
      function, with an average left ventricular stroke work index (LVSWI) of 19.9
      g.m/m2 (normal, 44 to 68 g.m/m2), whereas only 38% had concomitant right
      ventricular failure. This left-sided dysfunction persisted throughout the acute
      resuscitation period but was improved after appropriate modification of fluid
      resuscitation and initiation of vasopressors (average final LVSWI, 38.0 g.m/m2).
      There were no complications from placement of the Swan-Ganz catheters in this
      group. CONCLUSION: Cardiogenic failure is a major determinant of a failing
      pediatric burn resuscitation, and, contrary to the adult burn patient, the
      myocardial depression is predominantly left-sided. Information from pulmonary
      artery catheters can help direct therapy by providing indications for
      vasopressors and modifying fluid resuscitation.

PMID- 7738751
TI  - Evaluation of acute scrotum in the emergency department.
AB  - A 2-year retrospective review of 238 cases of acute scrotal pain encountered in a
      children's hospital emergency department is presented. The incidences of
      testicular torsion, torsion of a testicular appendage, and epididymitis were 16%,
      46%, and 35%, respectively. Testicular salvage was critically dependent on the
      interval between onset of pain and surgical intervention. No testis likely to
      have been viable at the time of presentation was "lost." The diagnostic error
      rate on first encounter was 7%, resulting in 10 negative scrotal explorations.
      With the exception of cases of far-advanced necrotic testes, both color Doppler
      ultrasound and radioisotope imaging were highly specific diagnostic modalities.
      Thirty-nine percent of the children with epididymitis who underwent investigation
      were found to have either structural or functional urinary tract abnormalities.
      Noninvasive urodynamic studies appear to be useful screening modalities in older
      children with epididymitis.

PMID- 7738752
TI  - Gastrocystoplasty: technical and metabolic characteristics of the most versatile
      childhood bladder augmentation modality.
AB  - The authors report on 23 patients who underwent complex continent urinary
      reconstructions, made successful by the selection of gastrocystoplasty as the
      chosen augmentation modality. The mean patient age was 6.1 years, and the mean
      weight was 17.9 kg. The minimum follow-up period was 1.5 years. The bladder
      capacity increased from a preoperative mean of 77.8 +/- 52.2 (SD) mL to a
      postoperative mean of 303.5 +/- 117.4 mL (P < .000001). No adverse effects on
      renal function or serum electrolyte composition were encountered, and there were
      no instances of acidosis or alkalosis. Continence was achieved in 91% of
      patients. In two patients (0.9%), hematuria-dysuria developed; one case was
      extremely mild. The other occurred only during a period of severe oliguria and
      resolved after transplantation. Gastrointestinal complications were minimal. Five
      patients had end-stage renal disease at the time of reconstruction and have since
      had successful transplantation. Gastrocystoplasty is particularly applicable to
      the pediatric population because of its unique anatomic and metabolic
      characteristics, which bestow tremendous versatility.

PMID- 7738753
TI  - Surgical management and outcome of locoregional neuroblastoma: comparison of the
      Childrens Cancer Group and the international staging systems.
AB  - Although precise anatomic staging is prognostically important in neuroblastoma,
      most widely employed staging systems remain incompatible. The International
      Neuroblastoma Staging System (INSS) was formulated to incorporate the basic
      elements of several systems to and define the significance of tumor
      resectability, anatomic "midline," and lymph node involvement. The authors sought
      to determine the applicability and value of the INSS compared with the classic
      Evans system. Between 1980 and 1992, 424 children with the diagnosis of local or
      regional neuroblastoma were entered in Childrens Cancer Group (CCG) clinical
      trials. The patients were assigned to Evans stage I, II, or III, by clinical and
      surgicopathologic assessment, and were treated uniformly by Group-wide therapy
      protocols. INSS stage 1, 2A, 2B, or 3, was applied, by retrospective analysis, to
      the children in the earlier studies, and by prospective evaluation of recent
      patients in the current studies. Survival and relapse-free survival (RFS) rates
      were determined and compared, based on age at diagnosis, extent of resection, and
      staging reassignment. All 87 Evans stage I patients were classified as INSS stage
      1 and had a 92% 3-year RFS rate. Of the 144 Evans stage II patients, 65 also
      qualified as INSS stage 1 patients, with an 82% RFS rate. The other 79 stage II
      children remained in INSS stage 2A or 2B and had a 70% RFS rate (P = .10). Of the
      193 Evans stage III patients, 24 were reassigned to INSS stage 1 (85% RFS rate)
      and 33 to stage 2A or 2B (65% survival rate; 61% RFS rate).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7738755
TI  - Urinary hyaluronic acid is a Wilms' tumor marker.
AB  - Wilms' tumor is a renal neoplasm that is histologically similar to fetal kidney
      tissue. Both Wilms' tumor and the fetal kidney have high levels of the
      glycosaminoglycan hyaluronic acid (HA) in the extracellular matrix. Preliminary
      studies suggest that urinary HA levels are elevated in Wilms' tumor patients. To
      test the utility of urinary HA as a Wilms' tumor marker, the authors compared HA
      levels in urine specimens from 105 Wilms' tumor patients with those of 17 age
      matched controls. Preoperative urine samples (n = 92), early postoperative
      samples, obtained from 1 to 3 weeks after surgery (n = 63), and late
      postoperative samples, obtained from 1 to 6 months after surgery (n = 58) were
      collected from patients at 30 institutions between 1989 and 1993. The HA levels
      were determined in triplicate by a competitive enzyme-linked immunosorbent
      binding assay. Seventy-four percent of the preoperative urine specimens contained
      elevated HA levels compared with the controls. The preoperative HA levels were
      significantly higher than the early postoperative (P < .01), late postoperative
      (P < .01), and control levels (P < .01). There was significant correlation
      between preoperative HA levels and clinical tumor staging. The mean preoperative
      HA level for patients with histological evidence of nephroblastomatosis was
      higher than that for patients without nephroblastomatosis. In the late
      postoperative period, patients with relapse or persistent disease had higher
      levels of urinary HA than did the disease-free patients (P < .05). In Wilms'
      tumor patients, urinary HA levels are elevated preoperatively and decline
      progressively after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738754
TI  - Biological variables in thoracic neuroblastoma: a Pediatric Oncology Group study.
AB  - The prognosis for patients with neuroblastoma is related to the age and stage at
      time of presentation, as well as to the presence or absence of biological markers
      such as N-myc amplification and the degree of DNA ploidy. However, previous
      studies have shown that neuroblastoma in the thoracic site also is a favorable
      prognostic indicator, in that children with mediastinal neuroblastoma have a
      better survival rate, regardless of age or stage at time of presentation. This
      study was designed to evaluate the biological differences between thoracic and
      nonthoracic neuroblastoma with respect to N-myc amplification, DNA index as a
      measure of DNA ploidy, serum lactate dehydrogenase levels, and serum ferritin
      levels. Patients enrolled in the Pediatric Oncology Group study protocols for
      neuroblastoma were evaluated retrospectively, and log-rank analysis allowed the
      impact of each biological variable on survival to be determined for each cohort
      of patients. There were 1,335 neuroblastoma patients in the data base; 227 had
      thoracic-site neuroblastoma. Through analysis, it was apparent that patients with
      thoracic neuroblastoma have better survival rates than do their nonthoracic
      counterparts (P < .0001), and they are less likely to have N-myc amplification (P
      = .001), more likely to have an LDH level of less than 1,500 (P < .0001), and
      usually have a DNA index of greater than 1 (P < .003). Both thoracic and
      nonthoracic patients have low serum ferritin levels (86% of thoracic versus 83%
      of nonthoracic patients).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738756
TI  - Devascularization and staged resection of giant sacrococcygeal teratoma in the
      premature infant.
AB  - Sacrococcygeal teratoma identified in utero is associated with 50% fetal demise,
      which is caused by hyperdynamic cardiac failure, hemorrhage, and polyhydramnios
      induced preterm labor. A premature infant (26 weeks' gestation) with prenatally
      diagnosed sacrococcygeal teratoma was managed successfully with initial
      devascularization to control the hyperdynamic state, followed by staged
      resection.

PMID- 7738757
TI  - The role of spiral (helical) computerized tomography with three-dimensional
      reconstruction in pediatric solid tumors.
AB  - The ability to accurately assess tumor size and orientation to surrounding vital
      structures is an important consideration during preoperative evaluation. The
      authors report on nine children with solid tumors (hepatoblastoma [1],
      neuroblastoma [2], adrenal cortical carcinoma [2], liver adenoma [1], primitive
      neuroectodermal tumor [PNET] [1], and stage V Wilms' tumor [2]) for whom tumor
      resectability was questioned because of the tumors' close proximity to major
      blood vessels (noted through conventional radiographic imaging). The children had
      scanning with spiral volumetric acquisition computerized tomography, (CT) which
      obtains images during continuous rotation of the x-ray source while the patient
      moves at a constant velocity through the gantry. This technique is rapid (18 to
      30 seconds), and is similar with respect to radiation exposure; little or no
      sedation is required, and the contrast dose is lower than that of conventional
      CT. Three-dimensional reconstruction of spiral CT imaging provided useful
      information that allowed successful resection in all nine cases. The authors
      suggest that spiral CT may become an important imaging modality in the
      preoperative evaluation of pediatric solid tumors and that further evaluation of
      this new methodology is warranted.

PMID- 7738758
TI  - Breast cancer in adolescent females.
AB  - Reports of breast cancer in adolescent females consist mostly of isolated
      patients. Because of this, neither the prognosis nor optimal management of the
      disease in this age group is clear. The authors retrospectively reviewed their 40
      year single-institution experience of all patients under 20 years of age who were
      referred for treatment of newly diagnosed breast cancer. The charts of 16
      patients, all females (age range, 13 to 19 years), were reviewed. Four patients
      found to have cytosarcoma phyllodes and two with tumors metastatic to the breast
      were excluded from further study. Ten patients had various forms of
      adenocarcinoma of the breast, including invasive intraductal, invasive lobular,
      signet ring, and secretory adenocarcinoma. Four had a family history of breast
      cancer. The average time from onset of symptoms to diagnosis was 3.7 months.
      Mammography failed to diagnose cancer in any of the four patients tested,
      including one with an 8-cm mass. Two patients had stage I tumors, four had stage
      IIA, two had stage IIIA, and two had stage IV. The patients were treated with
      combinations of surgery, radiation therapy, and chemotherapy. One stage I patient
      (with bilateral breast cancer) died of radiation-induced sarcoma after treatment;
      the other stage I patient is alive without disease 15 years after treatment. The
      5-year survival rate for stage IIA patients was 50%; that for patients with stage
      IIIA or IV was 0%. Five of the 10 patients presented during the past 10 years.
      This study constitutes the largest single institution experience with adolescent
      breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738759
TI  - Treatment of murine hemangioendotheliomas with the angiogenesis inhibitor AGM
      1470.
AB  - Hemangioma and other angiomatous diseases of childhood are common. Although most
      lesions are harmless and self-limiting, some are associated with significant
      morbidity and may be life-threatening. Interferon-alpha, a weak angiogenesis
      inhibitor, recently has been found to significantly reduce the mortality rate
      associated with life-threatening hemangiomas. The effectiveness of AGM-1470, a
      potent inhibitor of angiogenesis derived from the fungal product fumagillin, was
      tested in a mouse model of hemangioendothelioma. Thirty syngeneic mice were
      implanted with cells derived from a spontaneous mouse hemangioendothelioma.
      Tumors formed within 2 to 3 days, and the animals were then treated systemically
      with AGM-1470 or with saline and vehicle alone. After 22 days, the tumor volume
      in the saline-treated mice was 7368 +/- 2723 mm3, versus 709 +/- 73 mm3 in the
      mice that received AGM-1470 (P < .001). Survival was prolonged for the AGM-1470
      treated mice, and there was no evidence of drug-related toxicity. All experiments
      were repeated. In this study, AGM-1470 was safe and highly effective in the
      treatment of hemangioendothelioma. AGM-1470, and other antiangiogenic agents, may
      provide safe and effective treatment for hemangioma and other angiomatous
      diseases.

PMID- 7738760
TI  - Laryngotracheal disruption from blunt pediatric neck injuries: impact of early
      recognition and intervention on outcome.
AB  - Blunt and penetrating neck injuries are an infrequent cause of morbidity and
      mortality in the pediatric population. Although less common than penetrating
      injuries, blunt pediatric neck injuries are more often life-threatening because
      of associated laryngotracheal disruption. The authors reviewed their experience
      with pediatric neck injuries over the past 5 years. There were nine blunt and 14
      penetrating injuries, representing 0.5% of the trauma admissions. There was no
      significant difference in age or gender distribution between the two groups.
      Blunt pediatric neck injuries were more often associated with frank respiratory
      distress at the time of presentation. Massive subcutaneous emphysema and
      hoarseness were the most common symptoms encountered. All patients with blunt
      injury underwent direct laryngoscopy and bronchoscopy (DL & B) and esophagoscopy.
      DL & B results were positive for eight patients; seven patients underwent neck
      exploration and successful repair of the laryngotracheal injuries. There were two
      deaths; one of these patients had laryngeal transection, which was not recognized
      at the time of DL & B. The other death resulted from associated tracheobronchial
      disruption secondary to massive blunt chest trauma. The patients with penetrating
      neck injuries were more likely to be treated nonoperatively, to have a shorter
      stay in the hospital and intensive care unit, and to have a lower injury severity
      score. There were no deaths in this group. The authors conclude that all patients
      with blunt neck trauma should undergo emergent and meticulous DL & B.
      Visualization of laryngotracheal disruption mandates immediate neck exploration
      and primary repair.

PMID- 7738761
TI  - The efficacy of early ERCP in pediatric pancreatic trauma.
AB  - Recognition of pancreatic injuries is frequently delayed, and optimal treatment
      is often controversial. The use of endoscopic retrograde cholangiopancreatography
      (ERCP) has allowed accurate delineation of pancreatic ductal injuries; however,
      the small size of children and the concern with inducing pancreatitis and/or
      lesser sac contamination have limited its use in children. In 1988, the authors
      began using ERCP for selected pancreatic injuries. This report describes their
      experience with this technique and examines the role of ERCP in pediatric
      pancreatic injuries. Six children with pancreatic transections resulting from
      blunt trauma were treated between 1988 and 1993. The age range was 2 1/2 to 8
      years, and the weight range was 13.6 to 27.9 kg. The average period from injury
      to referral to the hospital was 14 days (range, 2 to 30 days). All six children
      presented with chemical evidence of pancreatitis and had an initial computed
      tomography (CT) scan; five scans were interpreted as being normal. Five of the
      six patients had subsequent CT scans, which showed lesser-sac fluid collection.
      Three patients were treated with drainage (2 percutaneous, 1 open [outside
      hospital]), and when this failed, ERCP was performed, at 13.6 days (average)
      after presentation. These three patients underwent ERCP relatively early in the
      course (an average of 3 days after presentation). All six children had major
      ductal transections documented through ERCP. After ERCP, the serum amylase level
      remained elevated in three, increased in one, and normal in one. (It was not
      measured in one of the recent cases taken for immediate operation.)(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7738762
TI  - Penetrating neck trauma in children: a reappraisal.
AB  - The management of penetrating neck injuries in adults is controversial, with a
      trend toward selective neck exploration. These injuries are uncommon in children,
      and only limited information exists regarding their management. To assess the
      management of these injuries in the authors' geographic region, they reviewed the
      records of children with injuries penetrating the platysma muscle who were
      treated between 1980 and 1994. Forty-six children (aged 2 to 16 years) suffered a
      total of 55 penetrating neck injuries. The injuries were classified according to
      type and location. Fifty-two percent were caused by missiles, 30% by stab wounds,
      and 18% by dog bites. Fifty-eight percent of injuries were in zone II, 31% in
      zone I, and only 11% in zone III. The diagnostic workup, including arteriography,
      esophagography, or endoscopy, was performed preoperatively in 10 patients.
      Overall, 21 patients had exploration, and the rate of negative explorations was
      48%. All cases explored for bleeding or a positive diagnostic workup result were
      found to have significant injury. On the other hand, all neck explorations
      performed solely because of injury to zone II were negative. The overall
      morbidity and mortality rates were 31% and 7%, respectively. A more selective
      approach, similar to that used for adult patients, emphasizing preoperative
      diagnostic evaluation, is recommended to decrease the rate of negative neck
      explorations among children.

PMID- 7738763
TI  - Extracorporeal membrane oxygenation as salvage in pediatric surgical emergencies.
AB  - Extracorporeal membrane oxygenation (ECMO) has become an established therapy for
      acute neonatal and pediatric respiratory failure. On an institutional level, once
      an ECMO program is well established, ECMO can be viewed as a logical extension of
      critical care for multisystem organ failure. The question left unanswered is
      "Should anyone die without being offered ECMO?" The authors reviewed a 10-year
      clinical experience with ECMO and its application as salvage therapy in pediatric
      surgical emergencies. Eight patients with life-threatening multisystem organ
      failure, from diverse causes, were treated; the survival rate was 50%. All
      survivors were neurologically intact at the time of discharge. The success of
      ECMO, coupled with improvements in technique, apparatus, and expertise, has
      allowed application of ECMO as an invasive extension of intensive care to diverse
      patient groups. These results have encouraged the authors to expand their
      indications and to push the "envelope" in offering ECMO to critically ill infants
      and children with life-threatening organ failure.

PMID- 7738764
TI  - Repair of congenital diaphragmatic hernia after weaning from extracorporeal
      membrane oxygenation.
AB  - Stabilization and delayed operation for patients with congenital diaphragmatic
      hernia (CDH) is now widely accepted. When preoperative extracorporeal membrane
      oxygenation (ECMO) is needed, most centers have CDH repaired on ECMO to minimize
      the risk of postoperative deterioration. The authors adopted a policy of weaning
      from ECMO before repair in an effort to avoid hemorrhagic risks. They reviewed
      their experience with CDH patients who required ECMO for stabilization before
      repair but for whom post-ECMO repair was planned. The records of all high-risk
      CDH patients with a gestational age of at least 34 weeks were reviewed. Eighteen
      patients were identified. None of the eight who were stabilized and operated on
      without ECMO required bypass postoperatively; all survived. Ten were placed on
      bypass, nine for stabilization before repair. Of the nine, seven (78%) were
      weaned from ECMO to conventional ventilation. Repair of the diaphragmatic defect
      was performed an average of 3.8 days later; none of these patients had severe
      pulmonary hypertension postoperatively, and all survived. Two could not be weaned
      before repair, one of whom had a complex congenital heart defect. This patient
      died. The other patient had repair on ECMO because of intrathoracic gastric
      volvulus. Severe blood loss prompted decannulation, and the patient died. One
      patient who was placed on bypass was transferred 10 days after having had repair
      elsewhere (at 4 hours of age). Pulmonary hypertension did not resolve, and the
      postmortem examination showed alveolar capillary dysplasia, with focal
      misalignment of the pulmonary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738765
TI  - The 'PLUG' odyssey: adventures in experimental fetal tracheal occlusion.
AB  - In animal experiments, it has been shown that tracheal occlusion counteracts the
      pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH).
      Successful clinical implementation requires a reliable, reversible, and
      atraumatic technique of occluding the fetal trachea. With this clinical goal in
      mind, the authors evaluated the following three methods of tracheal occlusion in
      a fetal lamb CDH model: (1) an occluded foam-cuffed endotracheal tube, (2) a foam
      cuffed endotracheal tube with a magnetically controlled flow valve, and (3) a
      tracheal insert constructed of a water-impermeable, expandable, polymeric foam,
      which is placed by a translaryngeal approach. The foam-cuffed endotracheal tube
      did not provide consistently reliable fetal tracheal occlusion. Although the
      magnetically triggered flow valve functioned well, it was not necessary to open
      the valve in utero (to prevent overdistension of the lungs), and the presence of
      the valve contributed to several occlusive failures. In contrast, the foam insert
      was easy to position and to remove from the trachea, while providing reliable
      tracheal occlusion for several weeks with consequent enlarged fetal lungs,
      increased lung fluid volumes, complete reduction of abdominal viscera, and
      improved pulmonary gas exchange after birth. Bronchoscopic evaluation of the foam
      occluded neonatal tracheas showed little or no tracheal damage, which was
      confirmed during necropsy by gross and histological examination. Translaryngeal
      placement of a compressible, water-impermeable polymeric foam appears to be a
      simple and safe technique to achieve fetal tracheal occlusion.

PMID- 7738766
TI  - Maintaining stereotypes in the face of disconfirmation: constructing grounds for
      subtyping deviants.
AB  - People encountering deviants who violate a stereotype try to maintain the
      stereotype by subtyping the deviants. They use the deviants' additional
      attributes to justify subtyping them. Participants read about counterstereotypic
      targets. Participants who were given no additional information about targets, and
      so had no grounds for subtyping them, did generalize from them and changed their
      stereotypes. However, participants who were told that targets had an additional,
      neutral attribute appeared to use it as grounds for subtyping them; their
      stereotypes remained unchanged. Participants came to view the neutral attributes
      as atypical of the stereotype and as associated with deviance, that is, as good
      reasons for subtyping the deviant. Neutral attributes blocked generalization from
      truly counterstereotypic targets but not from overly stereotypic ones, suggesting
      that their effect was due to participants' attempts to explain away individuals
      who strongly challenge their stereotypes.

PMID- 7738767
TI  - Self-other perception of the intensity of facial expressions of emotion: do we
      know what we show?
AB  - Participants' self-reports of the intensity of their facial expressive responses
      to an amusing stimulus were compared with judges' ratings in 2 studies. In
      Experiment 1, 24 men and 24 women who were alone and assigned to either a
      spontaneous or facial attention condition perceived their facial behavior to be
      significantly more expressive than judges' ratings indicated it had been. In
      Experiment 2, 36 men and 36 women who presumed themselves to be under observation
      were assigned to an uninstructed, pose, or communicate condition. Self-reports of
      expressive responses to an amusing stimulus again significantly exceeded judges'
      ratings in the first 2 conditions but not when participants were told to
      communicate their feelings.

PMID- 7738768
TI  - Cross-cultural correlates of life satisfaction and self-esteem.
AB  - College students in 31 nations (N = 13,118) completed measures of self-esteem,
      life satisfaction, and satisfaction with specific domains (friends, family, and
      finances). The authors assessed whether cross-cultural variations in the strength
      of associations were related to societal dimensions including income and
      individualism. At the national level, individualism correlated -.24 (ns) with
      heterogeneity and .71 (p < .001) with wealth. At the individual level, self
      esteem and life satisfaction were correlated .47 for the entire sample. This
      relation, however, was moderated by the individualism of the society. The
      associations of financial, friend, and family satisfactions with life
      satisfaction and with self-esteem also varied across nations. Financial
      satisfaction was a stronger correlate of life satisfaction in poorer countries.
      It was found that life satisfaction and self-esteem were clearly discriminable
      constructs. Satisfaction ratings, except for financial satisfaction, varied
      between slightly positive and fairly positive.

PMID- 7738769
TI  - Reassurance seeking, stress generation, and depressive symptoms: an integrative
      model.
AB  - The purpose of this study was to examine a mechanism through which interpersonal
      vulnerability factors may be linked with depressive symptoms by integrating a
      stress-generation model with an interpersonal theory of depression. The proposed
      conceptual framework was tested with 267 college students in a prospective
      structural equation model with 3 assessments over a 5-week period. Results
      supported all hypotheses. Initial depressive symptoms and initial reassurance
      seeking style were positively associated, and initial depressive symptoms were
      positively related to the occurrence of subsequent minor social stressors.
      Finally, a reassurance-seeking style was positively related to outcome depressive
      symptoms indirectly through minor social stressors. As predicted, stress
      generation operated as a mediating mechanism linking an initial reassurance
      seeking style to subsequent depressive symptoms.

PMID- 7738770
TI  - Sustained helping without obligation: motivation, longevity of service, and
      perceived attitude change among AIDS volunteers.
AB  - A conceptual framework that identifies psychological and behavioral features
      associated with antecedents, experiences, and consequences of volunteerism is
      presented, and an inventory that measures 5 specific motivations for AIDS
      volunteerism is developed and cross-validated. Then a field study of 116 AIDS
      volunteers is presented in which a helping disposition, volunteer motivations,
      and social support (as antecedents), and personal satisfaction and organizational
      integration (as experiences) are used to predict duration of service over 2 1/2
      years. Structural equation analyses indicate that dispositional helping
      influences satisfaction and integration but not duration of service, whereas
      greater motivation and less social support predict longer active volunteer
      service. The model is generalized to the prediction of perceived attitude change.
      Implications for conceptualizations of motivation, theoretical issues in helping,
      and practical concerns of volunteer organizations are discussed.

PMID- 7738771
TI  - Does hardiness contribute to mental health during a stressful real-life
      situation? The roles of appraisal and coping.
AB  - Israeli recruits (N = 276) completed questionnaires on hardiness, mental health,
      cognitive appraisal, and ways of coping at the beginning and end of a demanding,
      4-month combat training period. Path analysis revealed that 2 components of
      hardiness--commitment and control measured at the beginning of the training-
      predicted mental health at the end of the training through the mediation of
      appraisal and coping variables. Commitment improved mental health by reducing the
      appraisal of threat and the use of emotion-focused strategies and by increasing
      secondary appraisal. Control improved mental health by reducing the appraisal of
      threat and by increasing secondary appraisal and the use of problem-solving and
      support-seeking strategies.

PMID- 7738773
TI  - The thrill of victory, the complexity of defeat: self-esteem and people's
      emotional reactions to success and failure.
AB  - Low self-esteem people are assumed to have more severe emotional reactions to
      failure than are high self-esteem people, but this assumption has not received
      consistent empirical support. In this article the authors report 2 investigations
      that found that self-esteem differences of this sort emerge for emotions that
      directly implicate the self (e.g., pride, humiliation) but not for emotions that
      do not directly implicate the self (e.g., happiness, unhappiness). Additional
      evidence suggested that this occurs, in part, because low self-esteem people
      overgeneralize the negative implications of failure. The relevance of these
      findings for understanding the nature and functions of self-esteem is considered.

PMID- 7738772
TI  - Childhood conscientiousness and longevity: health behaviors and cause of death.
AB  - Previous research showed that conscientiousness (social dependability) in
      childhood predicted longevity in an archival prospective cohort study of bright
      children first studied by Terman in the 1920s (H. S. Friedman et al., 1993).
      Possible behavioral mechanisms for this robust association are now examined by
      gathering cause of death information and by considering the possible mediating
      influences of drinking alcohol, smoking, and overeating. Survival analyses (N =
      1,215) suggest that the protective effect of conscientiousness is not primarily
      due to accident avoidance and cannot be mostly explained by abstinence from
      unhealthy substance intake. Conscientiousness may have more wide-ranging effects
      on health-relevant activities.

PMID- 7738774
TI  - Parent ratings of EAS temperaments in twins, full siblings, half siblings, and
      step siblings.
AB  - A twin/family design was used to explore genetic contributions to personality; to
      evaluate whether twins and nontwins yield different genetic results; and to test
      for the presence of contrast effects, the tendency of a rater to contrast one
      sibling with the other, thereby magnifying existing behavioral differences. The
      sample consisted of 708 adolescent same-sex sibling pairs from 10 to 18 years of
      age. Pairs included identical (monozygotic; MZ) and fraternal (dizygotic; DZ)
      twins, and full siblings in nondivorced families; and full, half, and unrelated
      siblings in stepfamilies. Mothers and fathers rated the temperament of their
      children on the EAS Temperament Survey (A. H. Buss & R. Plomin, 1984). Model
      fitting analyses revealed significant genetic influences on each of the four EAS
      dimensions; however, for some dimensions, heritability estimates were
      significantly greater for twins than for nontwins. Overall, the data were best
      described by a sibling interaction model, which indicated significant contrast
      effects.

PMID- 7738775
TI  - [Interactive exhibition of heavy metal toxicity in bone metabolism. From the
      viewpoint of deductive toxicology].
AB  - "Toxicology" includes a broad range of application such as environmental,
      clinical and forensic toxicology. These several kinds of applied toxicology forms
      a mutually connected ring. This ring is supported by a column called as deductive
      and detective analysis by the author. "Deductive toxicology" is a way of thinking
      to solve toxicological problems more multidimensionally. In this paper, an
      application of this way to the study of bone lesions observed in Itai-itai
      diseased patients is described. In cultured embryonic chick bone, both cadmium
      and copper induced an atrophic change of the osseous tissue. However, zinc
      induced an osteomalacic change as a result of strong inhibition of calcification.
      These histological changes were supported by investigation using a culture system
      of osteoblastic MC3T3-E1 cells. Cadmium stimulated bone resorption in a neonatal
      parietal bone. In addition, cadmium stimulated the formation of osteoclast-like
      cells in bone marrow cell culture. It is thus suggested that cadmium and copper
      are factors of osteoporosis whereas zinc is a factor of osteomalacia when they
      directly act on bone tissues. A simultaneous exposure of cadmium and zinc to
      cultured bones resulted in an osteomalacic change with or without inhibition of
      bone matrix formation. Copper caused an atrophic change in the absence or the
      presence of zinc. A combination of cadmium and copper induced a severe damage of
      osteoblasts and osteogenic mesenchymal cells. These results suggested that an
      interactive exhibition of heavy metal toxicity can cause various bone lesions
      such as osteomalacia, osteoporosis and osteoporomalacia. The idea that heavy
      metals can directly act on bone tissues and their interaction can induce various
      histological changes in the tissue will help an understanding of bone lesions in
      Itai-itai disease.

PMID- 7738776
TI  - [Development of tracer methods in the drug evaluation study].
AB  - The development of the tracer methods in the drug evaluation study during the
      past thirty five years was reviewed. Several examples where stable isotope tracer
      techniques fully demonstrated their advantages were described. The applicability
      of 13C-NMR tracer techniques was discussed. The strategy for the metabolism study
      of peptides, microplate-radioluminography as a substitute for liquid
      scintillation counting and a quantitative whole body autoradiography were newly
      proposed.

PMID- 7738777
TI  - [Chemistry of benzoxazinoids produced by plants as phytoalexin].
AB  - 2,4-Dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one and its desmethoxy derivative
      (DIMBOA and DIBOA) are major phytoalexins produced by rye, wheat, zea maize and
      related monocotyledoneae plants. These compounds elicit a wide variety of
      biological activities including antifungal and mutagenic activities. Structure
      activity relationships of these compounds and their derivatives (benzoxazinoids),
      and the reactivity of benzoxazinoids with nucleophiles are discussed in relation
      to the molecular mechanism of their biological activity. The electrophilic
      reaction mechanism of benzoxazinoids and substituent effects of namely 7-methoxy
      and 2-hydroxy groups are also discussed.

PMID- 7738779
TI  - [Studies of novel 1,4-dihydropyridine Ca antagonist CS-905. I. Measurement of
      partition coefficient (log P) by high performance liquid chromatography (HPLC)].
AB  - A new 1,4-dihydropyridine derivative, CS-905, currently under development as a Ca
      antagonist, showed a gradual onset and long duration in its antihypertensive
      effect upon single oral administration. The partition coefficient for CS-905 was
      measured along with 11 known dihydropyridine Ca antagonists by the HPLC method to
      clarify its mode of action. The log PHPLC for CS-905 was, 5.18, almost the same
      as that of manidipine and this value is the highest among the measured drugs. Its
      pharmacokinetic profile in SHR was also discussed.

PMID- 7738778
TI  - [Inhibitory effects of sepimostat mesilate (FUT-187) on the activities of trypsin
      like serine proteases in vitro].
AB  - Inhibitory activities of FUT-187 on trypsin-like serine proteases were compared
      using camostat mesilate (camostat), and 4-(4-guanidino benzoyloxy)-phenyl acetic
      acid methanesulfonate (GBPA) known as an active metabolite of camostat in the
      blood. Ki values of FUT-187 on the competitive inhibition mechanism were 0.097
      microM for trypsin, 0.029 microM for pancreatic kallikrein, 0.61 microM for
      plasma kallikrein, 0.57 microM for plasmin, 2.5 microM for thrombin, 20.4 microM
      for factor Xa and 6.4 microM for C1r. However, FUT-187 acted as a noncompetitive
      inhibitor for factor XIIa and an uncompetitive inhibitor for C1s, and Ki values
      for these proteases were 0.021 and 0.18 microM, respectively. Ki values of
      camostat for these proteases were in the range of 0.037 to 96.4 microM, and those
      of GBPA for the above proteases except trypsin and plasma kallikrein were higher
      than those of FUT-187. The inhibitory activity of FUT-187 on trypsin was not
      reduced by the addition of the serum at 10%, whereas, that of GBPA was reduced
      (4.3 fold) in terms of IC50 values. The concentration of FUT-187 required to
      double APTT (activated partial thromboplastin time) was 1.09 microM, while GBPA,
      by concentrations up to 1 mM failed to double APTT. The kinin formation by
      glandular kallikrein in the rat plasma was inhibited by FUT-187 with IC50 value
      of 0.024 microM, while camostat revealed no inhibition by concentrations up to 1
      microM. The complement-mediated hemolyses in the classical and alternative
      pathways were also inhibited by FUT-187 with IC50 values of 0.17 and 3.5 microM,
      respectively, the corresponding values for camostat being 350 and 150 microM,
      respectively. It is concluded that FUT-187 is a potent and selective inhibitor of
      trypsin-like serine proteases, and its inhibitory activities are stronger than
      those of camostat on glandular kallikrein, factor XIIa and C1s in complement
      pathway.

PMID- 7738780
TI  - [Effect of the interaction of tannins with coexisting substances. VIII.
      Inhibitory effect of tannins on discoloration of natural pigments].
AB  - The discoloration of shikonin (1) and beta-carotene (2), occurring during storage
      of their ethanol solutions in the presence of oxygen in an illuminated room, was
      remarkably suppressed by hydrolyzable tannins, such as geraniin (4) and tannic
      acid JP (3) in the solution. The inhibitory effect of tannins was enhanced by the
      coexistence of metallic ion. The irradiation with ultraviolet lamp (254 and 365
      nm) gave, at the first stage of the discoloration, two products, one of which was
      found to be 5,8-dihydroxy-2-(1-hydroxy-3-oxo-4-methyl-4-pentenyl)-1,4
      naphthoquinone (7). The presence of hydrolyzable tannins induced higher
      accumulation of these two products in the solution, showing that the secondary
      structural transformations of these two products were strongly inhibited by these
      coexisting tannins. These results suggest that tannins could be efficient
      inhibitors of discoloration of natural pigments.

PMID- 7738782
TI  - [Simultaneous analysis of ginsenosides of various ginseng radix by HPLC].
AB  - A simultaneous analysis of ginsenosides in Panax ginseng by high performance
      liquid chromatography recently established by us was applied to the analysis of
      various Ginseng Radix. The contents of ginsenosides in P. ginseng were examined
      according to the differences of the growth year, the used part of the plant, the
      method of processing and the cultivated location. In the case of P. ginseng
      cultivated in Nagano, Japan, the ratio (total ginsenosides content/total dry root
      weight) increases annually for three years. And it decreased at the fourth year
      and increases again at the fifth and the sixth years. Concerning the distribution
      of ginsenosides in the parts of the plant, they were contained at the highest
      level in a lateral root and in succession, in a rhizome > in a root hair > in a
      main root. They were also distributed much richer at periderm than at phloem or
      at xylem of a main root. The contents of panaxadiol- and panaxatriol-saponins
      gradually increase with the growth year, whereas an oleananesaponin, ginsenoside
      Ro, drastically increases at the sixth year and goes to 15-fold, which suggests
      that the content of ginsenoside-Ro needs to be estimated much more when Ginseng
      Radix is evaluated. The fact that the processing for preparation of Red Ginseng
      increases the total content of saponins was clearly revealed by the present
      study. The highest contents of saponins among Red Ginsengs (all 6-year-old) were
      observed in ones prepared in Korea, and in Japan > in China, successively.

PMID- 7738781
TI  - [Determination of partial solubility parameters of lactoses and its application
      to solubility evaluation].
AB  - Partial solubility parameters of lactose packed into a glass column were
      calculated from adsorption energies of n-decane, acetonitrile and ethyl alcohol
      determined by gas-solid chromatography. Three kinds of crystalline lactoses,
      alpha-lactose monohydrate, anhydrous alpha-lactose (desiccated) prepared by
      desiccation with methyl alcohol, and anhydrous alpha-lactose (heated) prepared by
      heating, were used. It was characterized from the results that the partial
      solubility parameter, delta p, due to dipole interaction, of anhydrous forms had
      two-fold value than that of the hydrous form. In addition, it was suggested that
      the affinity of lactose for water vapor and the solubility of lactose for water
      were able to be evaluated using the three dimensional plot of partial solubility
      parameters and the interaction radius calculated from partial solubility
      parameters. It was shown that the appropriate information for the evaluation of
      physicochemical properties of active ingredients and excipients in the
      formulation study could be obtained from the data determined using partial
      solubility parameters.

PMID- 7738783
TI  - [Suppressive effects of iodinated contrast media on human platelet aggregation].
AB  - Suppressive effects of several iodinated contrast media on stimulus-induced
      aggregation of human platelets were demonstrated. All contrast media, including
      ionic (iothalamate and ioxaglate) and non-ionic ones (iohexol, ioversol and
      iopamidol), suppressed the collagen- and thrombin-induced aggregation in a
      concentration-dependent manner. The effects of the former were much stronger than
      those of the latter. With ioxaglate, a similar inhibitory effect was also
      observed on PAF- and U46619-stimulated aggregation. The suppressive effect of
      ioxaglate on collagen-stimulated aggregation almost disappeared upon dilution of
      the medium with the platelet-poor plasma, suggesting that the effect is
      reversible.

PMID- 7738784
TI  - A periplasmic insulin-cleaving proteinase (ICP) from Acinetobacter calcoaceticus
      sharing properties with protease III from Escherichia coli and IDE from
      eucaryotes.
AB  - A periplasmic insulin-cleaving proteinase (ICP), purified to its electrophoretic
      homogeneity in the SDS-PAGE from the Gram-negative bacterium Acinetobacter
      calcoaceticus, was examined and compared in its properties with the protease III
      (protease Pi, pitrilysin, EC 3.4.99.44) of Escherichia coli and the insulin
      destroying proteinase (IDE, insulinase, EC 3.4.99.45) from eucaryotes. The enzyme
      was proven to be a metalloprotease like protease III and IDE, as was shown by the
      inhibitory effects exerted by EDTA and o-phenanthroline. Furthermore, dialysis
      against EDTA and o-phenanthroline led to a complete loss of activity, which could
      be restored by addition of Co2+, and, to a lesser extent, but at a lower metal
      ion concentration by Zn2+. Similar to protease III and IDE, ICP prefers the
      cleavage of small polypeptides (insulin, insulin B-chain, glucagon) to the
      cleavage of proteins (casein, human serum albumin, globin) and was inactive
      against synthetic amino acid derivates (esters, p-nitranilides, and
      furoylacroleyl substrates) of subtilisin, thermolysin, trypsin, and chymotrypsin.
      The peptide-bond-specificity of the ICP in the cleavage of the oxidized insulin B
      chain was investigated and the results were compared to the specificity of
      protease III of E. coli, IDE, protease-24,11, and thermolysin. Cleavage sites in
      the oxidized insulin B-chain generated by ICP are Asn3-Gln4, His10-Leu11, Ala14
      Leu15, Leu17-Val18, Gly23-Phe24, Phe24-Phe25, and Phe25-Tyr26. Principally, ICP
      cleaves between hydrophobic amino acids and amides. The ICP shares one of the
      only two cleavage sites with the protease III and four sites with the IDE.

PMID- 7738785
TI  - Transformation reactions of progesterone by different species of Streptomyces.
AB  - A systematic study of transformation reactions of the genus Streptomyces with
      respect to the progesterone molecule was undertaken. The types of transformation
      reactions by different Streptomyces species were evaluated from the point of view
      of taxonomy. The isolates tested were divided according to the transformation
      types into six groups: (1) a group of species transform progesterone to 16 alpha
      hydroxyprogesterone; (2) a group of species transform progesterone to 6 beta
      hydroxyprogesterone; (3) a group of species transform progesterone to 6 beta, 11
      alpha-dihydroxyprogesterone; (4) a group of species dehydrogenate progesterone in
      C1-2 position; (5) a group of species transform progesterone to 3 derivatives
      namely 6 beta-hydroxyprogesterone, 6 beta, 11 alpha-dihydroxyprogesterone and
      dehydrogenation in position C1-2; (6) a group of species with no capacity to
      transform progesterone into another steroid derivative. From the point of view of
      Streptomyces classification, the transformation reaction of progesterone fulfil
      all the requirements of taxonomic feature of Streptomyces. These appear to be
      specific properties and common to all the strains of individual Streptomyces
      species tested.

PMID- 7738786
TI  - Effect of increased ppGpp concentration on DNA replication of different replicons
      in Escherichia coli.
AB  - The plasmids harbouring the relA gene under an inducible promoter allowed us to
      increase the guanosine 5'-diphosphate-3'-diphosphate (ppGpp) concentration in
      Escherichia coli cells without any starvation and thus, to directly investigate
      the effect of ppGpp on DNA replication. We studied all types of replicons which
      were investigated previously in amino acid-starved bacteria and found that ColE1,
      oriC, lambda plasmid and pSC101 but not RK2 replicons are sensitive to high ppGpp
      level. To our knowledge, this paper presents the first direct evidence that
      replication of most, but not all, replicons is dependent on ppGpp concentration
      and thus, is under stringent control.

PMID- 7738787
TI  - Thermally-induced cell lysis in Escherichia coli K12.
AB  - Escherichia coli cells exposed to high temperatures exhibit a progressive loss of
      viability. We observed two mechanisms of cell death induced by lethal
      temperatures: with and without lysis. The number of cells lysed by heat decreased
      at later stages of the growth curve, when cells were pre-treated at lower
      temperatures for 10 minutes and when cells were pre-treated with novobiocin,
      nalidixic acid and cadmium chloride. Cell lysis was similar in wild type, rpoH,
      groE and dnaK mutant cells as well as in cells which overproduce heat shock
      proteins GroE or DnaK. Results using cells aligned for cell division and cells
      growing at 42 degrees C, 45 degrees C and 47 degrees C suggest that cells near
      division are more sensitive to lysis and that a high concentration of heat-shock
      proteins increases their resistance to lysis.

PMID- 7738788
TI  - Pharmacokinetics of the acyl coenzyme A:cholesterol acyl transferase inhibitor CP
      105,191 in dogs--the effect of food and sesame oil on systemic exposure following
      oral dosing.
AB  - Inhibition of acyl coenzyme A:cholesterol acyl transferase (ACAT) decreases total
      plasma cholesterol in animals and may be an effective therapy for atherosclerosis
      in man. The pharmacokinetics of CP-105,191, a potent inhibitor of ACAT, were
      explored in fed and fasted dogs. Following oral administration of drug, mean
      apparent plasma half-life ranged from 9 to 16 h. Systemic availability of CP
      105,191, as determined by AUC(0-infinity), was approximately 3-4-fold higher in
      fed dogs than in fasted dogs when 50 mg doses were administered as aqueous
      suspensions. Tmax was achieved more rapidly and Cmax was lower in fasted dogs.
      When 50 mg doses, partially dissolved in 20 mL sesame oil, were administered to
      fed dogs, the availability of CP-105,191 increased by another factor of 2. A 12.5
      mg dose of CP-105,191, completely dissolved in sesame oil, was administered to
      fed and fasted dogs. Plasma AUC's were similar for fed and fasted dogs following
      the 12.5 mg dose, indicating that the increased availability of drug when
      administered with food is related to the presence of lipid.

PMID- 7738789
TI  - Metabolic activation and binding of mitotane in adrenal cortex homogenates.
AB  - Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane, o,p'-DDD] is
      an adrenocorticolytic agent of value in the treatment of adrenocortical carcinoma
      and Cushing's syndrome. In support of a program to develop agents superior to
      mitotane, it is the purpose of this study to explore the relationship of the
      metabolism of mitotane to its binding to adrenal cortex tissue from several
      sources. The objective was to detect the mitotane moiety responsible for its
      covalent binding in various test systems. Studies were conducted with an 125l
      labeled analog of mitotane, 1-(2-chlorophenyl)-1-(4-iodophenyl)-2,2
      dichloroethane, prior to a comparison to results with lower specific activity
      [14C]mitotane. With dog adrenal cortical whole homogenates, the majority of
      covalent binding was to proteins with an additional one-sixth of the total bound
      radioactivity associated with a phospholipid fraction. No radioactivity was
      associated with DNA. The rank order of species in regard to metabolism and
      protein binding was bovine > dog > rat adrenal homogenates > human normal adrenal
      or tumor homogenates. The percentage of radioactivity recovered from the
      hydrolysates of those fractions was uniformly high. In addition, the only
      metabolite present in the hydrolysates corresponded to 1-(2-chlorophenyl)-1-(4
      iodophenyl)acetic acid from the iodo analog of o,p'-DDD and the corresponding
      o,p'-dichlorodiphenylacetic acid (o,p'-DDA) from o,p'-DDD. Our results are
      consistent with an acyl chloride being the reactive intermediate formed from the
      dichloromethyl moiety of mitotane, which leads to both DDA metabolite formation
      and binding to adrenal cortical bionucleophiles.

PMID- 7738790
TI  - Characterization of native and drug-loaded human low density lipoproteins.
AB  - Low-density lipoproteins (LDLs), the physiological vehicles for lipids, are
      potentially useful drug delivery devices for (hydrophobic) drugs. The
      physicochemical characteristics of LDL loaded with the adriamycin derivative AD
      32 or the N-mustard derivative WB 4291 were compared to that of native and
      reconstituted LDL at different temperatures. X-ray solution scattering indicates
      that loading with AD 32 has no detectable effect on the particle structure at
      room temperature, in contrast to WB 4291. According to 19F NMR data, AD 32
      molecules are located in two distinct chemical environments with restricted
      motional freedom of the CF3 groups in samples stored as lyophilisates. 1H NMR
      signals from AD 32 were not observed, while those from WB 4291 could be
      distinguished from those of LDL constituents. WB 4291 molecules are in an
      environment with a higher motional freedom than AD 32 molecules. 1H NMR data
      suggest a higher fluidity of the core components for the WB-loaded LDLs compared
      to the other LDL preparations. While the motional freedom of the phospholipid
      head groups seems to be temperature independent, there is an increase in the
      mobility of the lipid components in the core region of the LDL particles with
      temperature.

PMID- 7738791
TI  - Displacement of one ligand by another calculated from the reverse displacement of
      the second ligand by the first.
AB  - This paper relates a generally applicable method for calculating mean
      displacement of a ligand, B, by another ligand, D, when the reverse displacement
      of D by B is known. The method is applied to calculating displacement of
      bilirubin from binding to albumin by a drug, warfarin or ceftriaxone. A binding
      isotherm for the drug to albumin is drawn, as the logarithm of free drug vs total
      drug concentration. A second binding isotherm is drawn for the drug in the
      presence of a certain concentration of bilirubin. The area between the two
      curves, up to a given total drug concentration, is measured and is divided by the
      concentration of bilirubin. The antilogarithm of the ratio is equal to the
      geometric mean of the ratio of free concentrations of bilirubin in the presence
      and absence of the drug when the bilirubin concentration varies from zero to the
      given value. The calculations are verified by comparing the direct determinations
      of the bilirubin displacing effect of the drugs by peroxidase kinetics.

PMID- 7738792
TI  - Pharmacokinetics of enoximone after various intravenous administrations to
      healthy volunteers.
AB  - The pharmacokinetics of enoximone and its sulfoxide metabolite were investigated
      in healthy male volunteers after various intravenous administrations: a bolus
      single dose, a continuous infusion, and bolus multiple doses of enoximone. The
      overall pharmacokinetic profiles of enoximone and sulfoxide metabolite indicated
      linearity over the range of 0.25-2.0 mg/kg after single doses of enoximone. The
      hypothetical plasma concentration just after bolus injection of enoximone, the
      maximum concentration of sulfoxide, and the area under the concentration-time
      curves of both compounds increased proportionally with dose. The terminal half
      lives of both compounds indicated similar values (2.0-2.7 h) and were not dose
      related. After four consecutive doses given at 3-h intervals, no accumulation was
      observed for either compound, and the pharmacokinetic parameters were not
      altered. After a 4-h infusion of enoximone, the areas under the plasma
      concentration-time curves of both compounds were 30% lower than the estimated
      values from the single dose study. Also, some pharmacokinetic parameters were
      changed as compared to those from the single dose study. The pharmacokinetic
      parameters obtained in Japanese healthy volunteers showed no marked differences
      from those obtained in Caucasians; thus, no racial difference was suggested in
      the pharmacokinetic properties of enoximone.

PMID- 7738793
TI  - Transdermal delivery of metoprolol. II: In-vitro skin permeation and
      bioavailability in hairless rats.
AB  - The absolute bioavailability of metoprolol (MP) was evaluated following oral and
      transdermal administration in hairless rats. The absolute bioavailability of MP
      following oral administration was 3.48 +/- 1.73%, indicating that MP is subject
      to extensive hepatic first-pass metabolism. Transdermal delivery of MP, via an
      adhesive delivery device, resulted in a bioavailability of 30.07 +/- 4.84%,
      indicating that the transdermal delivery of MP can significantly increase
      systemic bioavailability compared with oral administration. Preliminary skin
      irritation studies indicated that neither MP nor the adhesive used in the device
      caused any appreciable skin irritation in the hairless rats.

PMID- 7738794
TI  - Fourier transform infrared spectroscopic studies of cross-linked human serum
      albumin microcapsules. 3. Influence of terephthaloyl chloride concentration on
      spectra and correlation with microcapsule morphology and size.
AB  - Microcapsules were prepared from human serum albumin (HSA) by interfacial cross
      linking with terephthaloyl chloride (TC). TC concentrations were increased from
      0.5 to 5% w/v, while pH (9.8) and reaction time (30 min) were kept constant.
      Fourier transform infrared (FT-IR) spectra of lyophilized microcapsules were
      compared. Correlations were established with microcapsule morphology and size.
      The results were compared with those of previous studies exploring pH or reaction
      time and with those of parallel determinations of microcapsule free amino groups.
      With 0.5% TC, decreases of the ester-assigned 1724-cm-1 band area and of the
      carboxylate-assigned 1394-cm-1 band area were observed compared with pure HSA.
      This phenomenon was attributed to a removal of contaminating lipids of HSA.
      Increasing TC concentration resulted in a progressive increase of the band areas
      at 1724 cm-1 (esters) and 1795 cm-1 (anhydrides), in a further decrease of the
      1394-cm-1 band area (carboxylates), and in marked alterations of teh 1340-1080-cm
      1 region. These changes, which revealed the progressive acylation of hydroxy and
      carboxylate groups of HSA, were accompanied by an increase of the 1624-cm-1 band
      area (beta-sheet), reflecting interchain H-bonding due to cross-linking. As
      observed in the previous studies of pH and reaction time, important spectral
      changes corresponded to low values of -NH2 content, to a decrease in microcapsule
      mean size (from > 30 to < 15 microns), and to modifications of the membrane
      surface (made rough).

PMID- 7738795
TI  - Pharmacokinetics and body distribution of liposomal zinc phthalocyanine in tumor
      bearing mice: influence of aggregation state, particle size, and composition.
AB  - The pharmacokinetics and body distribution of zinc phthalocyanine (ZnPc)
      intravenously administered in liposomes composed of ZnPc, 1-palmitoyl-2
      oleoylphosphatidylcholine (POPC), and 1,2-dioleoylphosphatidylserine (OOPS)
      (1:90:10 or 1:70:30 w/w) to tumor (Meth A sarcoma) bearing mice were studied. It
      was found that aggregation of ZnPc in the liposomes (i) increases the clearance
      rate of the dye from plasma, (ii) lowers the maximal dye concentration in tumor
      tissue, and (iii) increases the maximal dye concentration in the liver. In
      addition, aggregated dye is hardly eliminated from the liver and monomeric dye is
      eventually completely eliminated from this organ. Liposomes in the size range of
      48-123 nm, containing the dye with the same aggregation state, showed the same
      pharmacokinetics and body distribution of the dye. The PS-content of the ZnPc
      liposomes (POPC alone versus POPC/OOPS 7:3) did not influence tumor, liver, and
      plasma pharmacokinetics during the studied time intervals. Free flow
      electrophoretic analysis showed in lyophilisates of ZnPc liposomes containing
      aggregated ZnPc the presence of two distinct populations differing in size,
      aggregation state of the dye, and PC/PS and ZnPc/phospholipid ratio. The
      liposomal formulation with monomeric ZnPc has a compositional homogeneity and
      demonstrated selectivity and reached high uptake in tumors, 48 h after
      intravenous administration and appears promising for photodynamic therapy.

PMID- 7738797
TI  - A Fourier transform-Raman and IR vibrational study of flurazepam base and the
      mono- and dihydrochloride salts.
AB  - Fourier transform (FT) Raman and IR spectra of flurazepam base and the mono- and
      dihydrochloride salts have been recorded. The parent compounds is 7-chloro-1-[2
      (diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro-[2H]- 1,4-benzodiazepin-2-one
      and is closely related to diazepam. The spectra show characteristic features
      associated with both the diazepine ring and substituents. Very strong lines near
      1615 cm-1 in the Raman spectra of the base and the monohydrochloride are assigned
      to the C = N stretch of the diazepine ring. The C = N group becomes a C = N+
      group in the dihydrochloride and the frequency shifts to 1635 cm-1. A very strong
      absorption near 1680 cm-1 in the IR spectra of the three compounds is attributed
      to the C = O stretching mode. The hydrochlorides are characterized by very strong
      broad bands in the IR spectra between 2600 and 2200 cm-1. Various IR and Raman
      vibrational features serve to characterize and differentiate the salts from each
      other and the free base. Raman and IR spectra have also been recorded for the
      related compound desalkylflurazepam [7-chloro-5-(2-fluorophenyl)-1,3-dihydro-[2H]
      1,4-benzodiazepin-2- one], in which a hydrogen atom replaces the
      (diethylamino)ethyl group at position 1 of the diazepine ring. Comparison of the
      spectra of this compound with those of flurazepam has enabled some vibrations of
      the (diethylamino)ethyl group to be identified.

PMID- 7738796
TI  - A prodrug approach to increasing the oral potency of a phenolic drug. Part 2.
      Pharmacodynamics and preliminary bioavailability of an orally administered O
      (imidomethyl) derivative of 17 beta-estradiol.
AB  - The O-saccharinylmethyl prodrug of 17 beta-estradiol was about nine times as
      potent, based on 50% effective dose (ED50) values, as 17 beta-estradiol when each
      was given as an oral dose to ovariectomized rats. Similarly, a significant
      lowering of follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
      levels at 24 h was observed when an ED50 dose of the prodrug was given but not
      when an equimolar dose of 17 beta-estradiol was given orally. However, when given
      intravenously, there was no difference in potency between the two drugs. In the
      bioavailability studies, a significantly longer half-life (approximately 5-7
      times) for 17B-estradiol was observed when the prodrug was given orally than when
      17 beta-estradiol was given orally or when the prodrug or 17 beta-estradiol were
      given intravenously. This result was consistent with an observed five-fold
      enhancement in the oral bioavailability of 17 beta-estradiol when the prodrug was
      given.

PMID- 7738798
TI  - In vitro and in vivo metabolism of the antianxiolytic agent fenobam in the rat.
AB  - Fenobam [(Fn); N-(3-chlorophenyl)-N-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2
      yl)urea] sulfate is a novel agent with potent anxiolytic activity in rats.
      [14C]Fn sulfate was administered as an oral solution (250 mg/kg) to male Wistar
      rats, and 52% of the administered dose was excreted in urine (0-5 days). In vitro
      metabolism of Fn was studied by incubating [14C]Fn with rat hepatic 9000 x g
      supernatant preparations. Unchanged Fn and a total of six metabolites were
      isolated, quantified, and identified from the urine and liver 9000 x g
      supernatant samples by column chromatography; TLC; UV, IR, and NMR spectroscopy;
      MS; and comparison with synthetic samples. Four metabolic pathways for Fn are
      proposed: (1) hydroxylation at the phenyl ring to form 4-hydroxyphenyl-Fn, a
      major pathway in vivo (12% of the sample radioactivity) but a minor pathway in
      vitro (4% of the sample radioactivity); (2) hydroxylation at the creatinine ring
      to form 5-hydroxy-Fn (19%) of the sample radioactivity), a dominant pathway in
      vitro but not in vivo; (3) oxidative cleavage at the creatinine ring (loss of a
      ketene unit), a minor pathway for Fn but an important pathway for 4-hydroxyphenyl
      Fn in vivo; and (4) N-demethylation, a minor pathway for Fn in vivo.

PMID- 7738799
TI  - Pressure-induced activity loss in solid state catalase.
AB  - The pressure-induced reductions in the activities of a number of enzymes in the
      solution state, and more recently in the solid state, have been reported. To
      further investigate the effect of pressure on proteins in the solid state, the
      enzyme catalase was used as a model. Compacts containing 150.0 +/- 0.2 mg of
      catalase powder were prepared on instrumented laboratory presses using various
      compaction pressures between 0 and 669 MPa. After compaction, a
      spectrophotometric assay was utilized to determine the pseudo-first-order rate
      constants for the catalase-catalyzed decomposition of hydrogen peroxide. These
      rate constants were used to calculate the change in catalase activity. Results
      indicated a loss in catalase activity of up to 30% at compaction pressures of 251
      MPa or greater. While the mechanism which produces the loss of enzyme activity is
      not clear, a strong linear correlation between enzyme activity and compaction
      pressure was seen over the range of pressures (0-251 MPa) where the decrease in
      activity occurred. In addition, compact densities were calculated and correlated
      to enzyme activity values. This correlation did not appear to be as strong.

PMID- 7738800
TI  - Enhancing effects of lipophilic vehicles on skin penetration of methyl nicotinate
      in vivo.
AB  - Vehicle effects may be caused by thermodynamic effects and by specific
      (penetration enhancing) effects. To investigate the effects of various lipophilic
      vehicles on drug penetration, an in vivo permeability study was conducted with
      methyl nicotinate as the model drug. The drug was dissolved in the respective
      vehicles at concentrations that provide equal drug escaping tendencies. Drug
      solutions were applied to the upper arms of volunteers with a glass chamber
      system. To avoid drug depletion effects, drug disappearance rates were measured
      under steady-state conditions by the difference method. Enhancement factors were
      calculated from the steady-state flux values (i.e., drug disappearance rates per
      area unit) and compared with results from non-steady-state experiments.
      Significant enhancing effects (p < 0.01) were observed with dibutyl adipate,
      caprylic/capric acid triglycerides containing 5% phospholipids, isopropyl
      myristate, and mineral oil. Caprylic/capric acid triglycerides, cetearyl
      isooctanoate, and the standard vehicle dimethicone 100 were without effect on
      drug penetration. The explanation for the observed enhancing effects may be an
      interaction of the lipophilic liquids with the lipid bilayers of the stratum
      corneum that leads to a decrease of the barrier resistance.

PMID- 7738802
TI  - Dissolution rate of cholesterol and palmitic acid mixtures in cholelitholytic
      cosolvent systems.
AB  - The dissolution rates and solubilities of cholesterol monohydrate, palmitic acid,
      and their mixtures in the cholelitholytic solvents monooctanoin (MO) and methyl
      tert-butyl ether (MTBE) and mixtures of these two solvents were determined. The
      dissolution rates obtained were consistent with the diffusion-controlled two
      component noninteracting model. The addition of MTBE as cosolvent to MO resulted
      in an increase in the solubility of both cholesterol monohydrate and palmitic
      acid; in the case of the former, the solubility peaked at 80% MTBE. Neither
      solute exhibited a log-linear solubility relationship on addition of MTBE as
      cosolvent. Furthermore the increases in the dissolution rates of both components
      were much larger than could be explained by the solubility increases alone. Mass
      transfer coefficients increased dramatically with increasing MTBE content of the
      solvent, were consistently higher for palmitic acid, and reflected the decline in
      solvent viscosity. Incorporation of relationships among solubility, viscosity,
      and cosolvent composition into the two-component noninteracting model gave good
      correlation between predicted and observed rates over nearly 3 orders of
      magnitude.

PMID- 7738801
TI  - Preparation and evaluation of Eudragit gels. VIII. Rectal absorption of 5
      fluorouracil from Eudispert hv gels in rats.
AB  - Rectal absorption of the hydrophilic 5-fluorouracil (5-FU) in rats was studied
      with Eudispert hv gels with or without fatty acids as the rectal bases. In the
      absence of fatty acids, absolute bioavailabilities of 5-FU for Eudispert hv
      hydrogel and xerogel preparations increased approximately 2.5 times compared with
      those of Witepsol H-15 and PEG 2000 suppositories. When n-capric acid or
      linolenic acid was used as an absorption enhancer, absolute bioavailabilities of
      5-FU were, respectively, 25.5 and 30.9% for Witepsol H-15 and 64.4 and 66.1% for
      PEG 2000. Furthermore, the absolute bioavailabilities of 5-FU for Eudispert hv
      hydrogel with n-capric acid or linolenic acid were 95.6% and 81.7%. The addition
      of capric acid or linolenic acid to the hydrogel was a useful method for
      increasing 5-FU permeability through the rectal membranes. These results are
      consistent with the observation that the total amounts of 5-FU remaining in the
      lumenal contents of the rectum and that accumulated in the rectal tissue
      decreased in relation to the increase in the bioavailabilities. Thus, the
      Eudispert hv hydrogel containing 5-FU with capric acid may be a useful rectal
      preparation for increasing the maximum plasma level and improving the absolute
      bioavailability of 5-FU.

PMID- 7738803
TI  - Isolation and structure elucidation of novel products of the acidic degradation
      of diazepam.
AB  - The acidic degradation of diazepam in methanolic aqueous solution has been
      investigated. Apart from the known degradation products, 2-(N-methylamino)-5
      chlorobenzophenone and glycine, produced by the hydrolytic cleavage of the
      benzodiazepinone ring, five novel products were isolated and fully characterized
      by their spectroscopic features and independent synthesis. Substituted 2-amino
      3,5-dichlorobenzophenones and 2,4-dichloroacridinones were found, the formation
      of which in the reaction media is mechanistically intriguing. The role of these
      unexpected products in accelerated studies of diazepam stability is discussed.

PMID- 7738804
TI  - Molecular weight of heparin using 13C nuclear magnetic resonance spectroscopy.
AB  - Heparin is a polydisperse, heterogeneous polysaccharide that has been used as an
      anticoagulant for the past 50 years. The molecular weight determination of this
      important drug has traditionally relied on gel permeation chromatography, which
      requires the use of well-defined molecular weight standards that are not easily
      obtained. We have investigated the use of 13C-NMR spectroscopy for measuring the
      number average molecular weight of heparin. The signal intensities of the
      reducing end and internal anomeric carbons, having distinctive chemical shifts in
      the 13C-NMR spectrum, were used to determine the molecular weight. Distortionless
      enhancement polarization transfer was found to provide a better quantitation of
      signal intensities of anomeric carbons than broad band decoupling or selective
      decoupling of anomeric protons. Signal averaging over 300,000 transients,
      requiring approximately 48 h on a 360 MHz NMR spectrometer, resulted in the
      measurement of the number average molecular weight (approximately 10,000 Da) of
      heparin. 13C-NMR spectroscopy does not require the use of difficult to obtain
      molecular weight standards and thus is particularly well-suited for workers in
      the pharmaceutical industry.

PMID- 7738805
TI  - In vitro cytotoxicities and in vivo distribution of transferrin-platinum(II)
      complex.
AB  - In vitro cytotoxic studies of protein-bound cis-diamminedichloroplatinum(II)
      (CDDP) against human epidermoid carcinoma A431 cells showed that transferrin (Tf)
      bound CDDP (Tf-Pt, Pt/Tf 7:1 mol/mol), and human serum albumin (HSA)-bound CDDP
      (HSA-Pt, Pt/HSA 7:1 mol/mol) exerted antiproliferating activities with IC50
      values of 7.2 and 85 microM, respectively. Tf-Pt inhibited the binding of 0.2 nM
      125I-labeled human diferric transferrin (hTf(Fe)2) to A431 cells with a
      inhibition constant (Ki) of 42 nM, whereas HSA-Pt did not. In vivo distribution
      studies showed that hTf(Fe)2, the Ki of which was 5.3 nM to mouse melanoma B16
      cells, was eliminated from plasma biexponentially in the B16-bearing and control
      mice after intravenous injection at a dose of 87 mg/kg, and AUCplasma values were
      29 and 39 mg.h/mL, respectively. In the B16-bearing mice the AUCtumor was 5.6
      mg.h/mL, while the AUCs of liver, kidney, and spleen were not distinguishable
      between the B16-bearing and control mice. Subsequently Tf-Pt (Pt/Tf 3:1 mol/mol)
      and free CDDP solution were administered intravenously to the B16-bearing mice.
      The systemic circulation of Pt was significantly prolonged by the administration
      of the complex. In conclusion, Tf could be a promising carrier protein for the
      transport of Pt to tumors.

PMID- 7738806
TI  - Safety of parenteral hydroxypropyl beta-cyclodextrin.
AB  - Post-treatment data were collected on a patient who received intravenous
      hydroxypropyl beta-cyclodextrin in a dose of 1.5 g/kg in 1985. Although no
      untoward effects were observed in this patient, rarely occurring agitation and
      pulmonary edema have been noted after injections into rabbits and dogs,
      respectively. These complications are analyzed here on the basis of symptoms and
      on the effects of hydroxypropyl beta-cyclodextrin on the biochemistry of a
      representative lipid, cholesterol, which were studied in rats. It is hypothesized
      that these untoward effects of parenteral hydroxypropyl beta-cyclodextrin are due
      to complex formation, with lipid mediators of pathological responses, of which
      prostaglandins are one example. These mediators normally have brief and localized
      functions; if hydroxypropyl beta-cyclodextrin happens to be injected when these
      mediator systems are activated, their influence and the responses of the organism
      may be increased.

PMID- 7738807
TI  - Comparison of the crystallinity of imipenem samples by X-ray diffraction of
      amorphous material.
AB  - The intensity of X-rays diffracted by amorphous material in samples of the beta
      lactam antibiotic imipenem [(5R,6S)-3-[[2-(formimidoyl-amino)ethyl]thio]-6-[(R)-1
      hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid] was used to
      compare the crystallinity of the samples. The method makes use of the intensity
      in the X-ray powder diffraction (XRPD) pattern at a diffraction angle of 28
      degrees (2 theta), at which no crystalline peaks are observed. A linear
      relationship (R2 = 0.9999) exists between amorphous intensity and crystallinity
      for synthetic mixtures of amorphous and crystalline imipenem. Sample preparation
      techniques ordinarily used in XRPD experiments were utilized.

PMID- 7738808
TI  - Determination of galactose in human blood by high-performance liquid
      chromatography: comparison with an enzymatic method and application to the
      pharmacokinetic study of galactose in patients with liver dysfunction.
AB  - Galactose, the C-4 epimer of glucose, is an agent of choice for the quantitation
      of liver function. A simple, precise, and accurate high-performance liquid
      chromatographic (HPLC) assay with refractive index detection was developed for
      the determination of galactose in human whole blood. The method consists of
      organic solvent-heavy metal deproteinization procedures and reversed-phase
      chromatography on a cation-exchange column in the calcium form. Calibration
      graphs were linear over the concentration range 100-2500 microgram/mL, with
      correlation coefficients > 0.999. The within-day coefficient of variation (CV)
      ranged from 2.08 to 8.94%, and the between-day CV ranged from 1.61 to 10.9%. The
      limit of quantitation was 100 micrograms/mL in whole blood. However, the limit of
      detection was 75 micrograms/mL based on a signal-to-noise ratio of > or = 3.
      Eight structurally related sugars and polyols were investigated to check for
      potential interferences using the analytical condition of the assay. The possible
      metabolites of galactose present in the body were also checked to determine the
      specificity of this assay. The proposed HPLC assay was compared with an enzymatic
      assay and an excellent correlation was observed (HPLC = 1.0299Enz. - 12.907, r =
      0.952, p < 0.001). This HPLC method has been successfully applied to the
      pharmacokinetic study of galactose in six patients with liver dysfunction.
      Following the intravenous administration of a dose of 0.5 g/kg body weight,
      galactose pharmacokinetics followed a nonlinear two-compartment model with
      Michaelis-Menten elimination from the central compartment.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7738809
TI  - Effects of the rate and composition of fluid replacement on the pharmacokinetics
      and pharmacodynamics of intravenous bumetanide.
AB  - The effects of differences in the rate and composition of intravenous (i.v.)
      fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of
      bumetanide were evaluated with rabbit as the animal model. Each rabbit received a
      4-h constant i.v. infusion of bumetanide at 1 mg/kg with 0% replacement
      (treatment I, n = 8), 50% replacement (treatment II, n = 6), and 100% replacement
      (treatment III, n = 7) with lactated Ringer's solution, in addition, another
      group of rabbits received 100% replacement with 5% dextrose in water (D-5-W,
      treatment IV, n = 4). Some pharmacokinetic parameters, such as the apparent
      volume of distribution at steady-state, mean residence time, and terminal half
      life, remained relatively unchanged in all four treatments. Renal clearance and
      urinary excretion rate of the drug in treatments I-III were essentially the same,
      but were considerably higher than those in treatment IV. In spite of the
      similarities in kinetic properties (approximately 40% difference between lowest
      and highest values), the diuretic and/or natriuretic effects of bumetanide were
      markedly different among the four treatments. For example, the mean 8-h urine
      output values were 189, 317, 2170, and 306 mL for treatments I-IV, respectively,
      the corresponding 8-h sodium excretion values were 9.19, 16.5, 88.8, and 15.7
      mmol, and the chloride excretion values were 10.8, 33.7, 77.4, and 11.7 mmol.
      Except for treatment III, diuresis and/or natriuresis were time dependent,
      generally decreasing with time until reaching a low plateau during later hours of
      infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738810
TI  - Rough sets in the analysis of the structure-activity relationships of antifungal
      imidazolium compounds.
AB  - The relationship between chemical structure and antifungal activity of quaternary
      imidazolium compounds is analyzed. The compounds are described by a set of
      condition attributes concerning structure and by a decision attribute concerning
      activity. The description builds up an information system. The smallest set of
      condition attributes, significant for high-quality classifications, has been
      found by using the rough sets approach. The analysis of the distribution of the
      value of the significant condition attributes in the best and the worst classes
      lead to the definition of typical representatives of the best and the worst
      imidazolium chlorides in terms of the significant condition attributes. A
      decision algorithm has been developed from the information system, presenting an
      important relationship between structure and antifungal activity. This may be
      helpful in supporting decisions concerning synthesis of new antifungal
      imidazolium compounds.

PMID- 7738811
TI  - Biodegradable microspheres. 16. Synthesis of primaquine-peptide spacers for
      lysosomal release from starch microparticles.
AB  - Classical procedures of peptide synthesis were applied to synthesize four groups
      of compounds, and analytical methods were developed for each of them. Two of the
      groups are tetrapeptide derivatives of the antileishmanial drug primaquine (PQ),
      with general structure NH2-X-Leu-Ala-Y-PQ. In the first group, Leu, Tyr, Lys, and
      Asp were used in the Y position, while X was Ala. In the second group, Ala, Tyr,
      Lys, and Asp were used in the X position, while Y was Leu. The derivatives are
      intended to be coupled, via their free alpha-amino group, to polyacryl starch
      microparticles, lysosomotropic drug carriers developed in our laboratory. Thus, a
      systematic study of the significance of the varying amino acid composition of the
      tetrapeptide spacer arm for the rate of lysosomal enzymatic release of PQ can be
      possible. A third group, comprising epsilon-aminocaproic acid-PQ derivatives
      which lack a free alpha-amino group, was synthesized. This was done to study the
      importance of enzymes, other than aminopeptidases, during lysosomal degradation
      of these derivatives. To allow HPLC analysis of the pattern of degradation of
      tetrapeptide-PQ derivatives, some shorter peptide-PQ derivatives (group four)
      were prepared as well.

PMID- 7738812
TI  - Biodegradable microspheres. 17. Lysosomal degradation of primaquine-peptide
      spacer arms.
AB  - The pharmacological activity of drugs bound to lysosomotropic drug carriers will
      depend on the rate of release of the drugs from the drug-carrier complex. We have
      now studied the enzymatic release of primaquine (PQ) from two groups of peptide
      PQ derivatives by their incubation with rat liver lysosomal fraction. The
      derivatives have the general structure NH2-X-Leu-Ala-Y-PQ and are intended to be
      coupled via their free alpha-amino group to starch microparticles. In the first
      group, Y was varied, being Leu, Tyr, Lys, or Asp, while X was Ala. In the second
      one, X was varied, being Ala, Tyr, Lys, or Asp, while Y was Leu. Thus, a
      systematic study of the significance of the varying amino acid composition of the
      tetrapeptides, which can serve as spacer arms in the microparticle-drug
      complexes, for the lysosomal release of PQ was possible. In addition, some
      epsilon-aminocaproic acid-PQ derivatives, which lack a free alpha-amino group,
      were incubated. This was done to study the importance of enzymes, other than
      aminopeptidases, during lysosomal degradation of these derivatives. The pattern
      and rate of degradation of all PQ derivatives was followed by HPLC analysis. The
      results obtained show that endopeptidases, as well as mono- and
      diaminopeptidases, degrade the derivatives. PQ cannot be cleaved directly from
      the derivatives by any carboxypeptidase-like enzyme. Asp peptides are digested
      slowly in the lysosomal fraction. The temporal aspects of reactions were
      quantitated using a kinetic model, in which first-order rate constants of all the
      steps of each peptide degradation sequence were estimated simultaneously.

PMID- 7738813
TI  - Synthesis and antiinflammatory, analgesic, and antipyretic testing of 4-[1-oxo-(3
      substituted aryl)-2-propenyl]-3-phenylsydnones and of 3-[4-[3-(substituted aryl)
      1-oxo-2-propenyl]phenyl]sydnones.
AB  - Two series of styrylcarbonyl 3-phenylsydnone derivatives, 4-[1-oxo-(3-substituted
      aryl)-2-propenyl]-3-phenylsydnones (series 1, 1-21) and 3-[4-[3-(substituted
      aryl)-1-oxo-2-propenyl]phenyl]sydnones (series II, 22-40), were synthesized and
      evaluated pharmacologically at a dose of 100 mg/kg po. Eleven compounds in series
      I plus one in series II and six in series I plus seven in series II were active
      in the carrageenan-induced edema and acetic acid-induced writhing assays,
      respectively. Compound 35 in the latter assay showed activity somewhat similar to
      that of the positive control drug, aspirin, administered at the same dosage.
      Compounds 11, 17, and 23 showed activity in both assays, and 23 also was active
      in the adjuvant-induced arthritis assay.

PMID- 7738814
TI  - Compatibility and stability of granisetron, dexamethasone, and methylprednisolone
      in injectable solutions.

PMID- 7738815
TI  - Role of talectomy in the treatment of rigid talipes equinovarus deformities.
AB  - The authors provide a review of the principles of talectomy as a surgical
      treatment option for severe, rigid, and resistant clubfoot deformities. Such
      deformities are associated with a high recurrence rate and frequently involve a
      large number of surgical interventions to attain a satisfactory result. Talectomy
      has been successfully used as both a primary and salvage procedure to treat such
      deformities, often eliminating the need for subsequent surgeries. A discussion of
      the operative technique, indications, advantages, and common complications
      associated with the procedure is presented. In addition, a case report of
      talectomy used to treat a severe, bilateral clubfoot deformity in a 4-year-old
      boy is included.

PMID- 7738816
TI  - Motion of the first metatarsophalangeal joint. Reliability and validity of four
      measurement techniques.
AB  - The purpose of this study was to first determine the intra-rater reliability of
      four different static measurement procedures used to assess first
      metatarsophalangeal joint extension range of motion and, second, determine which
      of the four static procedures provided a valid measure of the amount of first
      metatarsophalangeal joint extension required for normal walking. Twenty healthy
      adult subjects between the ages of 21 and 43 years participated in the study.
      Four static techniques were evaluated and dynamic first metatarsophalangeal joint
      extension was also determined from video recordings during walking. The results
      indicate that 1) all static measurement techniques were reliable; 2) the degree
      of first metatarsophalangeal joint extension obtained for each of the four static
      measurement techniques exceeded the amount of first metatarsophalangeal joint
      extension required for walking; 3) although each of the static measurement
      techniques was reliable, they should not be considered interchangeable; and 4)
      approximately 65 degrees of first metatarsophalangeal joint extension are
      required for normal walking.

PMID- 7738817
TI  - Superficial white onychomycosis.
AB  - A study on the incidence and causative organisms of pedal superficial white
      onychomycosis within several patient populations is presented. Early recognition,
      debridement, and topical antifungal therapy for several weeks with attention to
      biomechanical factors should resolve the infection and prevent progression to a
      more destructive form of onychomycosis.

PMID- 7738818
TI  - Evolutionary aspects of foot disorders.
AB  - The modern human foot can be viewed as the basic prehensile grasping foot of
      humans' arboreal ancestors, modified by the need for a propulsive lever to serve
      bipedal walking. The structure of the human foot serves its function remarkably
      well. However, in spite of its evolutionary success, the foot remains susceptible
      to clinical disorders that can be related to its development from nonhuman
      ancestors. An understanding of the evolution of the foot offers a different
      perspective on some common human foot disorders, and can provide a framework for
      planning the treatment of those disorders.

PMID- 7738819
TI  - Peroneal tenosynovitis secondary to peroneal tubercle osteochondroma and
      calcaneal varus.

PMID- 7738820
TI  - Maggot debridement therapy. An alternative treatment for nonhealing ulcers.
AB  - The authors illustrated a chronic bilateral plantar foot ulcer of several years'
      duration that was resistant to all forms of conventional therapy, yet was
      resolved after 13 1/2 weeks of maggot therapy. The contralateral foot ulcer
      showed no improvement during the same period, despite continual inpatient
      conventional dressing changes. At a time when medical cost containment is a
      critical issue, maggot therapy may resurge as a viable alternative in treating
      nonhealing wounds.

PMID- 7738821
TI  - Rickets. Return of an old disease.

PMID- 7738822
TI  - Osteochondrosis of the tarsal navicular in a female high school distance runner.
AB  - A case of osteochondrosis of the tarsal navicular in an adult is presented. The
      patient was not fully compliant with the recommendations of the physicians
      involved and, as a result, full recovery has not been accomplished. Left
      untreated or undertreated, Mueller-Weiss syndrome can result in severe permanent
      osteoarthritis of the midtarsal joint (talonavicular joint). This may result in
      permanent deformity and disability. Properly treated with rest and supportive
      therapy, the condition is self-limiting and should heal without any sequela.

PMID- 7738823
TI  - Crisis in the wings.

PMID- 7738824
TI  - Regulation of intracellular calcium and calcium buffering properties of rat
      isolated neurohypophysial nerve endings.
AB  - 1. Electrophysiological measurements of Ca2+ influx using patch clamp methodology
      were combined with fluorescent monitoring of the free intracellular calcium
      concentration ([Ca2+]i) to determine mechanisms of Ca2+ regulation in isolated
      nerve endings from the rat neurohypophysis. 2. Application of step
      depolarizations under voltage clamp resulted in voltage-dependent calcium influx
      (ICa) and increase in the [Ca2+]i. The increase in [Ca2+]i was proportional to
      the time-integrated ICa for low calcium loads but approached an asymptote of
      [Ca2+]i at large Ca2+ loads. These data indicate the presence of two distinct
      rapid Ca2+ buffering mechanisms. 3. Dialysis of fura-2, which competes for Ca2+
      binding with the endogenous Ca2+ buffers, reduced the amplitude and increased the
      duration of the step depolarization-evoked Ca2+ transients. More than 99% of Ca2+
      influx at low Ca2+ loads is immediately buffered by this endogenous buffer
      component, which probably consists of intracellular Ca2+ binding proteins. 4. The
      capacity of the endogenous buffer for binding Ca2+ remained stable during 300 s
      of dialysis of the nerve endings. These properties indicated that this Ca2+
      buffer component was either immobile or of high molecular weight and slowly
      diffusible. 5. In the presence of large Ca2+ loads a second distinct Ca2+ buffer
      mechanism was resolved which limited increases in [Ca2+]i to approximately 600
      nM. This Ca2+ buffer exhibited high capacity but low affinity for Ca2+ and its
      presence resulted in a loss of proportionality between the integrated ICa and the
      increase in [Ca2+]i. This buffering mechanism was sensitive to the mitochondrial
      Ca2+ uptake inhibitor Ruthenium Red. 6. Basal [Ca2+]i, depolarization-induced
      changes in [Ca2+]i and recovery of [Ca2+]i to resting levels following an induced
      increase in [Ca2+]i were unaffected by thapsigargin and cyclopiazonic acid,
      specific inhibitors of intracellular Ca(2+)-ATPases. Caffeine and ryanodine were
      also without effect on Ca2+ regulation. 7. Evoked increases in [Ca2+]i, as well
      as rates of recovery from a Ca2+ load, were unaffected by the extracellular
      [Na+], suggesting a minimal role for Na(+)-Ca2+ exchange in Ca2+ regulation in
      these nerve endings. 8. Application of repetitive step depolarizations for a
      constant period of stimulation resulted in a proportional frequency (up to 40 Hz)
      dependent increase in [Ca2+]i. On the other hand, for a constant number of
      stimuli a reduction in the [Ca2+]i. On the other hand, for a constant number of
      stimuli a reduction in the [Ca2+]i increase per impulse was observed at higher
      frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738825
TI  - Development of stiffness precedes cross-bridge attachment during the early
      tension rise in single frog muscle fibres.
AB  - 1. Force responses to ramp stretches were recorded in single muscle fibres
      isolated from the lumbricalis muscle of the frog. Stretches were applied at rest
      and at progressively increasing times after a single stimulus. 2. The increase of
      fibre stiffness that precedes tension development has a 'static' component that
      accounts for the whole fibre stiffness increase during the latent period and at
      very low tension at the beginning of the twitch. 3. Static stiffness increase was
      not affected by 2,3-butanedione-2-monoxime, a drug that almost completely
      inhibited twitch tension. 4. Static stiffness increased approximately 5-fold as
      the sarcomere length was increased from 2.1 to 2.84 microns. 5. These results
      suggest that static fibre stiffness increase is not attributable to the formation
      of non-force-generating cross-bridges.

PMID- 7738826
TI  - The effect of cardiac glycosides on the Na+ pump current-voltage relationship of
      isolated rat and guinea-pig heart cells.
AB  - 1. Whole-cell recording from isolated rat and guinea-pig ventricular myocytes
      revealed a change of the cardiac Na+ pump current (Ip)-voltage (V) relationship
      by cardiac glycosides, specific inhibitors of the Na(+)-K+ pump. 2. Dihydro
      ouabain (DHO) diminished Ip in rat ventricular cells at 0 mV in a concentration
      dependent manner. 3. The concentration-response curve of Ip inhibition caused by
      DHO was shifted to higher [DHO] at higher extracellular K+ concentrations ([K+]o)
      or at more negative membrane potentials. 4. In rat myocytes, DHO immediately
      flattened the normalized cardiac Ip-V curve and evoked or enhanced a region of
      negative slope. 5. Ouabain, at concentrations which caused a comparable
      inhibition of Ip, exerted DHO-like effects on the Ip-V relationship of rat
      ventricular myocytes. However, the effects developed more slowly. 6. A slowly
      developing alteration of the Ip-V curve was also observed upon application of DHO
      to guinea-pig ventricular cells. The range of [DHO] used was about 100-fold lower
      than that applied to rat ventricular cells, but was equally effective for Ip
      inhibition. 7. Increasing the K+ concentration of DHO-containing media affected
      the existing equilibrium of DHO binding to the cardiac Na(+)-K+ pump. A new
      equilibrium was reached within about 3 s in rat ventricular myocytes, but only
      within about 50 s in guinea-pig ventricular cells under the experimental
      conditions chosen. 8. It is concluded that the changes of the cardiac Ip-V curve
      induced by cardiac glycosides are mediated by voltage-dependent variations of the
      local [K+]o at the K+ binding sites of the Na(+)-K+ pump in an 'access channel'.
      The variations were estimated by means of the Boltzmann equation. The estimations
      agreed with those derived from the measured DHO binding to the Na(+)-K+ pump at
      various [K+]o. A new equilibrium of glycoside binding to the pump is established
      at the altered [K+]o. The time necessary to reach the new binding equilibrium
      varies with the cardioactive steroid, its concentration and the glycoside
      sensitivity of the cardiac cells.

PMID- 7738827
TI  - Gating mode conversion by proteolysis in a large-conductance K+ channel from
      embryonic rat telencephalon.
AB  - 1. In situ patch-clamp recordings of early embryonic large-conductance K+
      channels consistently revealed (86% of patches) a complex behaviour characterized
      by noisy fluctuations between open and closed states of relatively short
      duration. 2. This behaviour is similar to the buzz mode, a type of gating
      observed only very rarely in some channels. Its prevalence in proliferative
      neuroepithelium may thus constitute a criterion of immaturity. 3. In 89% of
      patches, the buzz mode was converted to a 'normal' mode by intracellular exposure
      to trypsin. 4. These observations suggest that the immature channel protein
      includes (or is affected by) a cytoplasmic component, the presence or absence of
      which determines certain sets of conformational transitions.

PMID- 7738828
TI  - Modulation of GABAC receptors in rat retinal bipolar cells by protein kinase C.
AB  - 1. The intracellular phosphorylation of bicuculline- and baclofen-insensitive
      GABAC receptors was investigated in rat retinal bipolar cells. The cells were
      recorded in organotypic slice cultures by using the whole-cell configuration of
      the patch-clamp technique. 2. Peak GABA responses recorded in the presence of
      bicuculline decreased with repetitive GABA applications. Intracellular
      application of the phorbol ester, phorbol 12-myristate, 13-acetate (PMA)
      increased this run-down, whilst it was prevented by both tamoxifen and
      phosphatase. 3. Perfusing the cells extracellularly with L-AP4, trans-(+/-)-1
      amino-1,3-cyclopentane dicarboxylate (ACPD) or alpha-methyl serotonin accelerated
      the run-down of GABAC responses. 4. Modulation of GABAC responses could be
      induced by intracellular application of GTP gamma S, indicating involvement of G
      proteins in the transduction cascade. 5. These results suggest that retinal GABAC
      receptors in bipolar cells are modulated by protein kinase C. Receptors which
      stimulate phospholipase C, presumably via Gi or Go, such as some of the
      metabotropic glutamate receptors or the 5-HT2 receptor, appear to be linked to
      this regulatory pathway.

PMID- 7738829
TI  - Facilitation of an NMDA receptor-mediated EPSP by paired-pulse stimulation in rat
      neocortex via depression of GABAergic IPSPs.
AB  - 1. Tight seal, whole-cell recordings from auditory cortex in vivo and in vitro
      were obtained to investigate modification of N-methyl-D-aspartate (NMDA) receptor
      mediated synaptic activity by paired-pulse afferent stimulation. 2. In recordings
      from urethane-anaesthetized rats (at 37 degrees C), or from cortical slices
      maintained in vitro (32 degrees C), afferent stimulation elicited a monosynaptic
      early EPSP and polysynaptic early and late IPSPs. In addition, a late EPSP could
      be elicited when the stimulus was preceded by an identical priming stimulus
      (interval approximately 200 ms). The late EPSP was attenuated by the NMDA
      receptor antagonist DL-2-amino-5-phosphonovalerate (APV, 50 microM). 3. Bath
      application of the gamma-aminobutyric acid-B (GABAB) receptor antagonist 3-amino
      2-(4-chlorophenyl)-2-hydroxy-propylsulphonic acid (2-OH-saclofen; 50 microM)
      attenuated the late IPSP and clearly revealed a late EPSP. However, 2-OH-saclofen
      had lesser effects on the second late EPSP elicited during paired-pulse
      stimulation. Membrane depolarization in 2-OH-saclofen increased the magnitude of
      the early IPSP, which suppressed the late EPSP once again. Since pharmacological
      blockade of EPSPs revealed paired-pulse depression of monosynaptically elicited
      early and late IPSPs, these data indicate that (1) both early and late IPSPs were
      capable of suppressing the late EPSP, and (2) these effects were reduced during
      paired-pulse stimulation. 4. Pharmacological isolation of the late EPSP allowed
      testing of the direct effect of paired-pulse stimulation. Application of 6-cyano
      7-nitroquinoxaline-2,3-dione (CNQX, 20 microM), picrotoxin (10 microM) and 2-OH
      saclofen (50 microM) isolated the late EPSP (onset, 3 ms; peak latency, 28 ms;
      peak amplitude, 7 mV; duration, 240 ms), which grew in magnitude with membrane
      depolarization and was largely (> 90%) blocked by APV. Paired-pulse stimulation
      depressed the isolated late EPSP by 30%. 5. Thus, apparent paired-pulse
      facilitation of the late EPSP is attributable to release from GABAergic
      inhibition, and not to direct facilitation. Facilitation of the late EPSP is a
      functional consequence of IPSP depression. The results indicate the importance of
      inhibition in regulating synaptic activity mediated by NMDA receptors.

PMID- 7738830
TI  - Inhibitory effect of adenosine on electrical activity of frog melanotrophs
      mediated through A1 purinergic receptors.
AB  - 1. The effects of adenosine were studied in cultured frog melanotrophs by the
      patch-clamp technique. 2. In cell-attached experiments, most cells responded to
      adenosine (50 microM) by a reversible inhibition of action current discharges
      without any apparent desensitization. 3. In whole-cell experiments, adenosine
      provoked a hyperpolarization accompanied by a depression of spontaneous action
      potentials and a decrease in membrane resistance. When adenosine was repeatedly
      applied, tachyphylaxis was observed. Addition of GTP (100 microM) in the
      intracellular solution augmented the percentage of cells hyperpolarized by
      adenosine, and the duration and amplitude of the hyperpolarization, and prevented
      the tachyphylaxis. 4. Pretreatment with pertussis toxin (1 microgram ml-1)
      blocked adenosine-induced inhibition. 5. In cells dialysed with the non
      hydrolysable GTP analogue GTP gamma S (100 microM), adenosine caused a sustained,
      strong hyperpolarization and an irreversible inhibition of spikes. 6. The effect
      of adenosine was mimicked by the A1 receptor agonist R-PIA (R-N6-phenylisopropyl
      adenosine; 50 microM) and blocked by the A1 receptor antagonist CPDPX (8
      cyclopentyl-1,3-dipropylxanthine, 50 microM). The A2 receptor antagonist CGS15943
      (9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo[1,5-c] quinazoline-5-imine; 50
      microM) did not affect the adenosine-induced response. 7. The results suggest
      that, in frog melanotrophs, adenosine exerts a direct hyperpolarizing effect
      accompanied by blockage of spontaneous action potentials. The effect of adenosine
      is mediated through A1 receptors coupled to a Gi/o protein.

PMID- 7738831
TI  - Kinetic separation of charge movement components in intact frog skeletal muscle.
AB  - 1. Procedures for a complete charge movement separation employed a combination of
      its steady-state inactivation and activation properties in intact frog skeletal
      muscle fibres in gluconate-containing solutions. 2. Holding potential shifts from
      -70 to -50 mV reduced the total charge available between -90 and -20 mV from
      16.76 +/- 1.70 nC microF-1 (mean +/- S.E.M.; n = 4 fibres) to 9.25 +/- 1.43 nC
      microF-1 without significant loss of tetracaine-resistant charge (q beta). 3. The
      steady-state and kinetic properties of tetracaine-sensitive charge (q gamma)
      persisted through holding potential changes from -90 to -70 mV in the presence of
      gluconate and generally resembled activation properties established hitherto in
      sulphate-containing solutions. 4. Further holding potential displacement to -50
      mV abolished q gamma charge movements and depressed the charge-voltage curve. 5.
      Test voltage steps applied from a -70 mV prepulse level gave rapid monotonic q
      beta decays and similarly depressed activation functions in 2 mM tetracaine
      unchanged by holding potential shifts between -70 and -50 mV. 6. The isolated
      'on' q gamma charge movements, I(t), always included early transients that
      preceded any prolonged charging phases and which increased with depolarization.
      They decayed to stable baselines in the absence of prolonged time-dependent or
      inward-current phases and yielded integrals, Q(t), that monotonically increased
      with test voltage. 7. 'Off' steps always elicited rapid monotonic q gamma decays
      that fully returned the 'on' charge. 8. 'On' and 'off' q gamma currents, I(t),
      following voltage steps from fixed conditioning to varying test levels mapped
      onto topologically distinct higher-order phase-plane trajectories, I(Q), that
      steeply varied with test voltage. 9. In contrast, voltage steps to fixed test
      potentials of either -70 or -20 mV elicited identical q gamma phase-plane
      trajectories independent of prepulse history. 10. The q gamma current thus
      reflects an independent, capacitative process driven uniquely by higher-order
      dependences upon charge distribution, Q(t), and test voltage, V(t), autonomous of
      prepulse history or time, t.

PMID- 7738832
TI  - Excitatory synaptic connections onto rat hippocampal inhibitory cells may involve
      a single transmitter release site.
AB  - 1. Whole-cell tight-seal records of excitatory postsynaptic currents (EPSCs) were
      made from inhibitory cells in the CA3 region of thin hippocampal slices. We
      tested the hypothesis that excitatory synaptic connections made on inhibitory
      cells involve few transmitter release sites. 2. EPSCs impinging on inhibitory
      cells had a time to peak of 0.4-3.8 ms and an amplitude of 8-90 pA at a holding
      potential of -60 mV. They were suppressed by the excitatory amino acid
      antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and DL-2-amino-5
      phosphonovaleric acid (APV). 3. Addition of tetrodotoxin (TTX) and Co2+ to the
      external solution reduced the frequency of EPSCs from 0.90 to 0.25 s-1 (n = 24
      cells). In the majority of cells EPSC amplitude distributions were not
      significantly changed. 4. Increasing Ca2+ and reducing Mg2+ in the external
      solution, in order to enhance the probability of transmitter release, did not
      change EPSC amplitude distributions. In contrast, amplitude histograms for IPSCs
      recorded from pyramidal cells were shifted to higher mean values in this
      solution. 5. EPSCs were elicited in inhibitory cells by electrical stimulation
      via a glass pipette placed near to pyramidal cells in stratum pyramidale. EPSCs
      elicited by weak stimuli had similar amplitude distributions to excitatory
      synaptic events recorded in the presence of TTX and Co2+. 6. These findings
      suggest excitatory synaptic connections made with CA3 inhibitory cells involve
      few or possibly just one transmitter release site.

PMID- 7738833
TI  - Characterization of endothelium-derived hyperpolarizing factor as a cytochrome
      P450-derived arachidonic acid metabolite in mammals.
AB  - 1. In addition to nitric oxide (NO) and prostacyclin (PGI2) an as yet
      unidentified endothelium-derived hyperpolarizing factor (EDHF) contributes to the
      dilator effect of bradykinin in different vascular beds. We have investigated the
      nature and mechanism of action of this factor in freshly isolated bovine and
      porcine coronary artery segments which were preconstricted with the thromboxane
      mimetic U46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2
      alpha, 10-30 nM). 2. The concentration-response curve of bradykinin was
      significantly shifted to the right after inhibition of NO synthesis with NG-nitro
      L-arginine (L-NNA, 30 microM), whereas cyclo-oxygenase blockade with diclofenac
      (1 microM) had no effect. Preconstriction of the segments with potassium chloride
      (40-60 mM) completely abrogated the NO/PGI2-independent dilator response to
      bradykinin. In sandwich bioassay experiments, both the luminal and abluminal
      release of NO, but not that of EDHF, was readily detectable. 3. Inhibitors of
      Ca(2+)-activated K+ channels (K+Ca), such as apamin (1 microM) and
      tetrabutylammonium (TBA, 3 mM), strongly attenuated the EDHF-mediated bradykinin
      induced relaxation, while glibenclamide (3 microM), an inhibitor of K+ATP
      channels, had no effect. 4. These relaxations were also significantly inhibited
      by the phospholipase A2 inhibitor, quinacrine (30 microM), and the cytochrome
      P450 inhibitors, SKF525a (30-100 microM) and clotrimazole (100 microM). Moreover,
      incubation of endothelium-denuded coronary artery rings with a cytochrome P450
      derived arachidonic acid metabolite, 11,12-epoxyeicosatetraenoic acid, elicited a
      concentration-dependent (1-10 microM) dilatation which was abolished both in the
      presence of TBA (3 mM) and following preconstriction of the segments with
      potassium chloride instead of U46619.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738834
TI  - Mediation of excitatory neurotransmission by the release of ATP and noradrenaline
      in sheep mesenteric lymphatic vessels.
AB  - 1. Spontaneous isometric contractions were measured in rings of sheep mesenteric
      lymphatics. Field stimulation at short pulse widths increased the frequency of
      spontaneous contractions and this response was blocked by 3 x 10(-7) M omega
      conotoxin and by 10(-6) M guanethidine. 2. Rings that had been incubated with
      [3H]noradrenaline release 3H in response to field stimulation in a frequency
      dependent manner. 3. Exogenous ATP mimicked the response to field stimulation and
      this was blocked by 10(-4) M suramin but not by prior desensitization with 10(-6)
      M alpha, beta-methylene ATP. Exogenous noradrenaline was not blocked by 10(-4) M
      suramin. 4. The excitatory response to field stimulation was not blocked by 10(
      4) M suramin but a combination of 10(-4) M suramin and 3 x 10(-6) M phentolamine
      did block the response. 5. In rings taken from sheep that had been pretreated
      with reserpine, 10(-4) M suramin alone blocked the response to field stimulation.
      6. The results of this study suggest that the excitatory response to stimulation
      of intramural nerves in sheep mesenteric lymphatics is mediated by the release of
      both ATP and noradrenaline.

PMID- 7738835
TI  - Urinary kallikrein in the rat: stimulation with angiotensin infusion but
      depression with increasing sodium concentration.
AB  - 1. The kallikrein response to angiotensin II infusion in the conscious rat was
      studied to compare it with the response in the dog. 2. Active kallikrein was
      measured by the aprotinin-suppressible esterase technique in 20 min periods.
      Angiotensin (5 x 10(-9) to 5 x 10(-2) micrograms min-1) was infused in 10 mM
      saline in period 10 (group A), or in 90 mM saline in periods 10-12 (group B). 3.
      In group A, no dose of angiotensin was antinatriuretic. Natriuresis and urinary
      sodium concentration were dose dependent. 4. Kallikrein excretion was dose
      dependent with angiotensin (P < 0.0001) and inversely correlated with urinary
      sodium concentration (P = 0.011). In natriuretic and non-natriuretic rats,
      kallikrein excretion after angiotensin was inversely correlated with urinary
      sodium concentration in the preceding period. 5. In group B, natriuresis and
      urinary sodium concentration were dose dependent. Kallikrein excretion in periods
      10-13 was inversely correlated with urinary sodium concentration in the preceding
      period (P = 0.0001) and inversely correlated with urinary osmolality in periods 9
      13. 6. Infusion of angiotensin II at 5 x 10(-6) micrograms min-1 led to
      antinatriuresis. 7. Formulae were derived which enabled the opposing effects of
      angiotensin and urinary sodium concentration on kallikrein excretion to be
      separated. In group A both these effects were statistically significant only in
      the natriuretic rats (natriuresis > 20 mumols per period). In group B the
      formulae showed a dose-dependent rise in kallikrein excretion, which was
      counteracted by the decrease in kallikrein excretion associated with the
      increasing urinary sodium concentration. 8. With infusions of 0.9% saline,
      kallikrein excretion in periods 10-13 was inversely correlated with urinary
      sodium concentration in the preceding period (P = 0.001). 9. The overall effect
      in the rat differs from that in the dog, where kallikrein increases with
      angiotensin natriuresis and dilution of the urine occurs.

PMID- 7738836
TI  - Intramural neural pathways between the duodenum and sphincter of Oddi in the
      Australian brush-tailed possum in vivo.
AB  - 1. Balloon distension of the duodenum 2 cm oral or anal to the sphincter of Oddi
      duodenal junction elevated the amplitude of spontaneous sphincter of Oddi phasic
      contractions by 37.7 +/- 8.5 or 120.1 +/- 79.8%, respectively (mean +/- S.E.M.,
      both n = 6, P < 0.05, Wilcoxon test). To further investigate this response, this
      study aimed to determine if: (i) electrical field stimulation (EFS) of the
      duodenum influences sphincter of Oddi activity; (ii) intramural nerves mediate
      the response; and (iii) nicotinic and/or muscarinic receptors are involved. 2.
      Electrical field stimulation (70 V, 0.5 ms; 5-60 Hz, 10-20 s) of the duodenal
      anterior serosal surface 2-4 cm oral or anal to the sphincter of Oddi-duodenal
      junction, produced excitatory responses in the sphincter of Oddi in anaesthetized
      Australian brush-tailed possums (n = 45). 3. These responses were frequency
      dependent, maximal at 30 Hz (n = 4) and abolished by tetrodotoxin (9 micrograms
      kg-1 I.A.; n = 6), or by crushing the duodenum (n = 3). Hexamethonium bromide (30
      mg kg-1 I.V.) did not significantly alter the response to duodenal EFS either
      oral (n = 6) or anal (n = 8) to the sphincter of Oddi-duodenal junction. Atropine
      sulphate (30 micrograms kg-1 I.V.) reduced the response to duodenal EFS oral and
      anal to the sphincter of Oddi-duodenal junction to 11.2 +/- 5.8 (n = 6) and 45.0
      +/- 26.8% (n = 8), respectively (both P < 0.05). 4. Bilateral cervical vagotomy
      and guanethidine infusion (10 mg kg-1 over 15 min I.V.) did not significantly
      alter the responses to duodenal EFS (n = 7). 5. Excitatory intramural neural
      pathways between the sphincter of Oddi and the segment of duodenum 4 cm oral and
      anal to the sphincter of Oddi-duodenal junction have been demonstrated. These
      postganglionic pathways may involve muscarinic receptors.

PMID- 7738837
TI  - Effect of dynamic exercise on left atrial function in conscious dogs.
AB  - 1. Dynamic changes in left atrial (LA) function during treadmill exercise were
      studied in ten conscious dogs instrumented to measure left ventricular (LV)
      pressure and diameter, LA pressure and diameter, and pulmonary venous blood flow
      (PVF, transit time flowmeter). 2. Systolic PVF volume (reservoir volume; a
      measure of LA reservoir function) increased from 38 +/- 4% of total PVF volume at
      baseline to 52 +/- 8% of total PVF volume during exercise, and diastolic PVF
      volume (conduit volume; a measure of LA conduit function) decreased from 62 +/-
      5% at baseline to 48 +/- 8% during exercise (P < 0.005). 3. The increases in
      reservoir volume and the decrease in conduit volume were due not only to a
      greater decrease in diastolic interval than systolic interval but were also
      caused by a significantly greater increase (P < 0.05) in the mean systolic
      filling rate (93%) than in the mean diastolic filling rate (51%). 4. During
      exercise the pattern of LV filling derived from changes in LV diameter showed
      that a greater percentage of LV filling occurred during the second half of
      diastole at the time of atrial contraction (P < 0.05), suggesting that LA booster
      function was enhanced. 5. Changes in LA dimension revealed that during exercise
      more blood volume was reserved in the LA during systole and that this change was
      associated with an increase in the LA dimension at the beginning of LA
      contraction (r = 0.61, P < 0.05). 6. We conclude that LA reservoir and booster
      functions were augmented during exercise, whereas conduit function was not.
      Increased reservoir function may play an important role in accelerating LV
      filling by helping to maintain an enhanced atrioventricular pressure gradient
      during diastole and also by increasing LA booster function through an increase in
      LA preload.

PMID- 7738838
TI  - Conditioning effect in single human motoneurones: a new method using the unitary
      H reflex.
AB  - 1. A new method for the study of spinal reflexes using single motor units is
      described. 2. The excitability of a motoneurone is assessed as the 'critical
      firing stimulus' (CFS), which is the difference between the test stimulus
      intensity needed to reach the threshold for the lowest threshold Ia fibres and
      the intensity which evokes firing of a motor unit with the probability of 50%
      (FP50%). The intensity with FP50% is obtained by modulating stimulator output.
      When the motor unit is fired by a stimulus, the next intensity is decreased, and
      vice versa. The Ia threshold is defined as the threshold for homonymous
      monosynaptic peaks in PSTHs during contraction of the muscle examined. 3. A
      conditioning effect is represented as a change in CFS, the extent being expressed
      as a percentage of the unconditioned CFS. 4. Effects obtained by conditioning
      stimulation with the new and conventional H reflex methods are compared. The
      sensitivities are almost the same and the extents of the effects have highly
      correlated linear relations for the two methods. 5. The advantages of the new
      method are (1) that it shows reflex activities on a single motoneurone, (2) that
      it is applicable both to muscles at rest and during contraction, and (3) that it
      quantifies conditioning effects as percentages of the size of test Ia EPSPs.

PMID- 7738839
TI  - Effects of deep breaths on subsequent ventilation in man during rest and
      exercise.
AB  - 1. We examined the effects of twenty-four to thirty inspiratory capacity (IC),
      expiratory capacity (EC) and vital capacity (VC) breaths on subsequent breathing
      pattern in five normal subjects at rest. 2. During IC breaths and following EC
      and VC breaths at rest, end-tidal CO2 pressure (PET,CO2) fell by 7.5, 8.5 and 9.5
      mmHg, respectively. In the group analysis significant inhibition of ventilation
      of 1.5 l min-1 was seen after the IC breath but not after EC or VC breaths. 3. We
      repeated the study with five normal subjects under conditions of higher
      ventilatory drive, namely 50 W exercise (one subject was common to both groups).
      4. During exercise, the drop in PET,CO2 was smaller (4.0, 3.5 and 4.0 mmHg,
      respectively, with IC, EC and VC breaths) but ventilation was inhibited to a
      greater extent. Ventilatory undershoot was seen after all three types of deep
      breaths. 5. We propose that the expiration to residual volume in EC and VC
      breaths abolished the hypocapnic inhibition of ventilation at rest, possibly by a
      deflation reflex which was not sufficiently powerful to overcome the ventilatory
      undershoot during exercise. Our results also support the view that the slope of
      the CO2 response curve is steeper near the control point during exercise.

PMID- 7738841
TI  - Response of arm flexor muscles to magnetic and electrical brain stimulation
      during shortening and lengthening tasks in man.
AB  - 1. The responses of the brachioradialis and biceps brachii muscles to non
      invasive magnetic and electrical stimulation of the human motor cortex have been
      investigated during performance of different tasks. 2. Both muscles were
      simultaneously active during elbow flexor isometric torque, or forearm flexion
      lifting a weight (shortening contraction), or extension breaking the fall of the
      weight (lengthening contraction). The forearm extensor triceps brachii muscle was
      not engaged in any task. By using different weights, comparable levels of EMG
      activity were obtained in the same muscle across tasks. 3. Both magnetic (7
      subjects) and electrical (3 subjects) brain stimulation (at about 1.5 times the
      motor threshold) produced larger responses during shortening, and smaller
      responses during lengthening, in the brachioradialis muscle with respect to
      isometric contractions, in spite of equal background EMG levels. Responses evoked
      in the biceps brachii by either stimulation mode were smaller during lengthening
      but not significantly enhanced during shortening. No consistent differences in
      the task-related modulation of the responses were present between electrical or
      magnetic stimulations. No significant changes in the evoked responses occurred
      during passive elbow flexion or extension. 4. In three subjects, the H reflex was
      evoked in the brachioradialis by stimulation of the radial nerve during
      performance of the same tasks. The pattern of task-related modulation of the
      reflex amplitude paralleled that obtained for brain stimulation. 5. The opposite
      modulation induced by the shortening and lengthening tasks both in magnetically
      and electrically evoked motor responses, and in the H reflex, suggests that task
      related changes in excitability of the cortical neurones play a minor
      role.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738840
TI  - Depression of Renshaw recurrent inhibition by activation of corticospinal fibres
      in human upper and lower limb.
AB  - 1. This study tested whether the recurrent inhibition of soleus and wrist flexor
      motoneurones could be modified by transcranial magnetic stimulation in human
      subjects. 2. Magnetic stimulation was given through a circular coil centred at
      the vertex. The intensity of the magnetic stimulus was subthreshold for evoking a
      motor response in the active soleus and wrist flexor muscles. The recurrent
      inhibition brought about by a conditioning H1 reflex discharge was estimated by a
      test H' reflex. The modifications of the recurrent inhibition after cortical
      stimulation were distinguished from the motoneuronal changes by comparing H' to a
      reference H reflex. 3. In the soleus motoneurones, the reference H reflex was
      inhibited at a minimum conditioning-test interval of -2 ms (H reflex stimulus
      before magnetic stimulation). In contrast, the H' reflex was facilitated at
      minimum conditioning-test intervals of +1 ms. In the wrist flexor motoneurones,
      both H' and reference H reflexes were facilitated. However, at lower cortical
      stimulus intensities, only the H' reflex was facilitated at minimum conditioning
      test intervals of +1 ms. 4. In both motoneurone pools, H' facilitation started 3
      4 ms later than the earliest changes in the reference H reflex. Also, the
      threshold of H' facilitation was lower than that of reference H reflex. 5. It is
      concluded that facilitation of the H' reflex is produced by corticospinal
      inhibition of Renshaw cells via a short interneuronal chain in both the upper and
      lower limb.

PMID- 7738842
TI  - The processing of human ballistic movements explored by stimulation over the
      cortex.
AB  - 1. When seated human subjects abducted one arm rapidly in response to a tone
      there was successively a burst of electromyographic (EMG) activity in the deltoid
      and latissimus dorsi muscles followed by another burst in the deltoid muscle.
      This triphasic pattern is typical of a ballistic 'focal movement'. There were
      also bursts of EMG activity in the contralateral latissimus dorsi, pectoralis
      major and abdominal muscles, which were assumed to be 'associated postural
      adjustments'. The same bilateral pattern of muscle activity occurred in a
      deafferented subject. 2. When subjects abducted the left arm rapidly, magnetic
      stimulation over the left motor cortex delayed the onset of the EMG burst in the
      right latissimus dorsi relative to the initial burst in the left deltoid. When
      subjects abducted the right arm rapidly, magnetic stimulation over the left motor
      cortex delayed the onset of the initial EMG burst in the right deltoid relative
      to the burst in the left latissimus. In each case, the delay of an EMG burst was
      greatest (about 80 ms) when the stimulus was given just before the burst was
      expected to occur. The inhibition of voluntary movements by transcranial
      stimulation was not associated with a reduction in the excitability of spinal
      motoneurons. 3. We conclude that focal ballistic movements and their associated
      postural adjustments are generated in exactly the same way. We postulate that
      these movements are preprogrammed, held in a memory until the 'go' signal and
      then released through both motor cortices to spinal motoneurons.

PMID- 7738843
TI  - Flexibility of lower limb reflex responses to painful cutaneous stimulation in
      standing humans: evidence of load-dependent modulation.
AB  - 1. In six human subjects standing without support, the reflex response of the
      tibialis anterior muscle (TA) was elicited by painful electrical stimulation (500
      Hz, 20 ms) of the anterior sole of the foot and analysed by post-stimulus
      averages of rectified electromyography. The threshold intensity for the reflex
      response was very close to the subjective pain sensation (mean value, 1.05
      times). Estimation of the afferent conduction velocity gave a mean value of 26.5
      m s-1, suggesting that a contribution from A delta fibres was necessary to evoke
      the reflex response. The TA reflex response was then used as the pain test
      reflex. 2. Changes in the TA excitatory pain reflex response (elicited at 1.2
      times the pain threshold) were investigated while the subjects maintained
      different postures in upright stance. Standing on the ipsilateral leg produced a
      significant decrease in the reflex response with respect to its value in
      symmetrical stance (standing on both legs), whereas a significant facilitation
      was observed when the subject was standing on the contralateral leg. A parallel
      depression of the response in both limbs was present when the subject maintained
      an upright stance with the lower limbs abducted. Thus, it was apparent that the
      TA pain responses decreased as the supporting function of the leg increased. 3. A
      significant inverse correlation between the load to which the limb was subjected
      and the size of the reflex response was observed in all subjects. We propose that
      the load to which the limb is subjected, measured from peripheral
      mechanoreceptors, is used as a measure of the current supporting function of the
      limb, on the basis of which the reflex is regulated.

PMID- 7738844
TI  - Characterization of Ca2+ channel currents in cultured rat cerebellar granule
      neurones.
AB  - 1. High-threshold voltage-gated calcium channel currents (IBa) were studied in
      cultured rat cerebellar granule neurones using the whole-cell patch clamp
      technique with 10 mM Ba2+ as the charge carrier. The putative P-type component of
      whole-cell current was characterized by utilizing the toxin omega-agatoxin IVA
      (omega-Aga IVA) in combination with other blockers. 2. omega-Aga IVA (100 nM)
      inhibited the high voltage-activated (HVA) IBa by 40.9 +/- 3.4% (n = 27), and the
      dissociation constant Kd was 2.7 nM. Maximal inhibition occurred within a 2-3 min
      time course, and was irreversible. The isolated omega-Aga IVA-sensitive current
      was non-inactivating. 3. omega-Aga IVA exhibited overlapping selectivity with
      both N- and L-channel blockers; omega-conotoxin GVIA (omega-CTX GVIA) (1 microM)
      and the dihydropyridine (-)-202-709 (1 microM), respectively. Together these
      toxins reduced the omega-Aga IVA-sensitive component to just 4.5 +/- 1.4% (n =
      3). Thus only a small proportion of the current can be unequivocally attributed
      to P-type current. Inhibition of the HVA IBa by omega-Aga IA also reduced the
      proportion of omega-Aga IVA-sensitive current to 28.0 +/- 3.2% (n = 3). 4.
      Application of omega-Aga IVA and a synthetic form of funnel-web toxin, N-(7-amino
      4-azaheptyl)-L-argininamide (sFTX-3.3; 10 microM), produced an additive block of
      the HVA IBa. Consequently these two toxins do not act on the same channel in
      cerebellar granule neurones. 5. omega-Aga IVA inhibition of low voltage-activated
      (LVA) IBa was studied in the ND7-23 neuronal cell line. omega-Aga IVA (100 nM)
      reduced the LVA current by 41.3 +/- 3.2% (n = 17) in a fully reversible manner
      with no shift in the steady-state inactivation of the channel. 6. A component of
      current insensitive to N-, L- and P-channel blockers remained unclassified in all
      our studies. This component, and also that remaining following block by omega-Aga
      IVA and omega-Aga IA, exhibited relatively rapid, although incomplete,
      inactivation compared to the other currents isolated in this study. 7. In
      conclusion, omega-Aga IVA inhibits a component of current in cultured cerebellar
      granule neurones which overlaps almost completely with that inhibited by L- and N
      channel blockers. In addition, a large component of whole-cell current in these
      neurones still remains unclassified.

PMID- 7738845
TI  - Neurotransmitter release evoked by nerve impulses without Ca2+ entry through Ca2+
      channels in frog motor nerve endings.
AB  - 1. The requirement for extracellular Ca2+ in the process of evoked acetylcholine
      (ACh) release by nerve impulses was tested at endplates in frog skeletal muscle.
      Ca(2+)-containing lipid vesicles (Ca2+ liposomes) were used to elevate
      cytoplasmic Ca2+ concentrations under conditions in which Ca2+ entry from the
      extracellular fluid was prevented. 2. In an extracellular solution containing no
      added Ca2+ and 1 mM Mg2+ ('Ca(2+)-free' solution), Ca2+ liposomes promoted the
      synchronous release of ACh quanta, reflected electrophysiologically as endplate
      potentials (EPPs), in response to temporally isolated nerve impulses. 3. Motor
      nerve stimulation generated EPPs during superfusion with Ca2+ liposomes in Ca(2+)
      free solutions containing the Ca2+ channel blocker Co2+ (1 mM), and the Ca2+
      chelator EGTA (2 mM). As a physiological control for Ca2+ leakage from the
      liposomes to the extracellular fluid, the effect of Ca2+ liposomes on
      asynchronous evoked ACh release mediated by Ba2+ was examined. In contrast to the
      effects of 0.2-0.3 mM extracellular Ca2+, which generated EPPs but antagonized
      Ba(2+)-mediated asynchronous ACh release, Ca2+ liposomes generated EPPs but did
      not reduce asynchronous release mediated by Ba2+. The effects of Ca2+ liposomes
      were thus not due to leakage of Ca2+ from the liposome to the extracellular
      fluid. 4. Morphological studies using fluorescently labelled liposomes in
      conjunction with a confocal microscope demonstrate that lipid is transferred from
      the liposomes to nerve endings and liposomal contents are delivered to the nerve
      terminal cytoplasm. 5. The results suggest that when intracellular Ca2+ is
      elevated using liposomes as a vehicle, evoked ACh release can occur in the
      absence of Ca2+ entry via Ca2+ channels.

PMID- 7738846
TI  - Nitric oxide donors enhanced Ca2+ currents and blocked noradrenaline-induced Ca2+
      current inhibition in rat sympathetic neurons.
AB  - 1. The effects of NO donors on Ca2+ channel currents and noradrenaline (NA)
      induced Ca2+ current inhibition were investigated in superior cervical ganglion
      (SCG) neurons using the whole-cell patch-clamp technique. 2. A 500 microM
      concentration of the NO donors, sodium nitroprusside (SNP) and S-nitroso-N
      acetylpenicillamine (SNAP), enhanced Ca2+ current amplitude after either
      extracellular or intracellular application. The magnitude of Ca2+ current
      enhancement induced by NO donors was greater after intracellular application than
      after extracellular application. 3. Intracellular application of 1 mM guanosine
      3',5'-cyclic monophosphate (cGMP) or 100 microM M&B 22948 (2-O-propoxyphenyl-8
      azapurine-6-one), a cGMP phosphodiesterase inhibitor, or extracellular
      application of 1 mM 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) also
      increased the amplitude of Ca2+ currents thus mimicking the effect of the NO
      donors on Ca2+ channels. In contrast, pretreatment with Methylene Blue (100
      microM) decreased the SNP (500 microM)-induced enhancement of Ca2+ currents. 4.
      Intracellular application of 500 microM SNP and SNAP, 100 microM M&B 22948 or 1
      mM cGMP, or extracellular application of 200 microM 8-Br-cGMP reduced the
      magnitude of Ca2+ current inhibition induced by 5 microM NA. In addition, 500
      microM SNP prevented the NA-induced shift of tail current activation curves to
      more depolarized potentials. 5. Internal dialysis with 500 microM SNP and SNAP or
      1 mM cGMP, or extracellular application of 200 microM 8-Br-cGMP, reduced Ca2+
      current facilitation produced by a depolarizing conditioning pulse both in the
      absence and presence of 5 microM NA. 6. The results suggest that NO donors induce
      enhancement of Ca2+ currents and block NA-induced Ca2+ current inhibition of SCG
      neurons via stimulation of cGMP formation.

PMID- 7738847
TI  - Quantal puffs of intracellular Ca2+ evoked by inositol trisphosphate in Xenopus
      oocytes.
AB  - 1. Ca2+ liberation induced in Xenopus oocytes by a poorly metabolized derivative
      of inositol 1,4,5-trisphosphate (3-deoxy-3-fluoro-D-myo-inositol 1,4,5
      trisphosphate; 3-F-InsP3) was visualized using a video-rate confocal microscope
      to image fluorescence signals reported by the indicator dye calcium green-1. 2.
      Low (10-30 nM) intracellular concentrations of 3-F-InsP3 evoked Ca2+ release as
      localized transient 'puffs'. Progressively higher concentrations (30-60 nM) gave
      rise to abortive Ca2+ waves triggered by puffs, and then (> 60 nM) to a sustained
      elevation of Ca2+ followed by the appearance of propagating Ca2+ waves. At
      concentrations up to that giving waves, the frequency of puffs increased as about
      the third power of [InsP3], whereas their amplitudes increased only slightly. 3.
      The rise of cytosolic Ca2+ during a puff began abruptly, and peaked within about
      50 ms. The peak free Ca2+ level was about 180 nM, and the total amount of Ca2+
      liberated was several attomoles (10(-18) mol), too much to be accounted for by
      opening of a single InsP3-gated channel. The subsequent decline of Ca2+ occurred
      over a few hundred milliseconds, determined largely by diffusion of Ca2+ away
      from the release site, rather than by resequestration. Lateral spread of Ca2+ was
      restricted to a few micrometres, consistent with an effective diffusion
      coefficient for Ca2+ ions of about 27 microns2 s-1. 4. The peak amplitudes of
      puffs recorded at a given site were distributed in a roughly Gaussian manner, and
      a small proportion of sites consistently gave puffs much larger than the main
      population. Intervals between successive puffs at a single site were
      exponentially distributed, except for a progressive fall-off in puffs seen at
      intervals shorter than about 10 s. Thus, triggering of puffs appeared to be
      stochastically determined after recovery from a refractory period. 5. There was
      little correlation between the occurrence of puffs at sites more than a few
      micrometres apart, indicating that puff sites can function autonomously, but
      closely (ca 2 microns) adjacent sites showed highly correlated behaviour. 6.
      Puffs arose from sites-present at a density of about 1 per 30 microns2 in the
      animal hemisphere, located within a narrow band about 5-7 microns below the
      plasma membrane. 7. We conclude that Ca2+ puffs represent a 'quantal' unit of
      InsP3-evoked Ca2+ liberation, which may arise because local regenerative feedback
      by cytosolic Ca2+ ions causes the concerted opening of several closely clustered
      InsP3 receptor channels.

PMID- 7738848
TI  - The role of the Na(+)-Ca2+ exchanger in the rate-dependent increase in
      contraction in guinea-pig ventricular myocytes.
AB  - 1. The intracellular sodium activity (alpha Na1), contraction and membrane
      current were recorded simultaneously in voltage-clamped guinea-pig ventricular
      myocytes. 2. Increasing the frequency (from 0.5 to 3 Hz) of voltage clamp pulses
      to 0 mV from a holding potential of -80 mV led to an increase in both alpha Na1
      and contraction. The rate-dependent increase in contraction was reduced by 25
      microM tetrodotoxin (TTX) and abolished with a holding potential of -40 mV. There
      was no rate-dependent rise in alpha Na1 with a holding potential of -40 mV. These
      results suggest an important role for alpha Na1 and in particular Na+ influx via
      Na+ channels during rate-dependent changes in contraction. 3. After an increase
      in frequency from 0.5 to 3 Hz, membrane current at the end of voltage clamp
      pulses became progressively more outward and the tail current upon at
      repolarization became progressively more inward compared with those recorded at
      0.5 Hz. TTX reduced the magnitude of both the outward and inward rate-dependent
      shifts of current. 4. The addition of extracellular CsCl blocked the inward
      rectifier potassium current (IK.1) and the delayed rectifier (IK), but did not
      change the rate-dependent shift in current. 5. The difference between current
      voltage relationships at 0.5 and 3 Hz showed that the rate-dependent outward
      shift of current at the end of voltage clamp pulses was small at potentials
      negative to -20 mV, was larger at more positive potentials and was reduced by TTX
      at most potentials. The TTX-sensitive component reversed at -47 mV. 6. These
      results are consistent with a net increase in outward Na(+)-Ca2+ exchange current
      during a voltage clamp pulse in response to the rise of alpha Na1. The increase
      in outward current (resulting from either enhanced Ca2+ influx or reduced Ca2+
      efflux) will augment the Ca2+ load of the cell and contribute to the rate
      dependent increase in contraction.

PMID- 7738849
TI  - Identification of an ATP-dependent copper transport system in endoplasmic
      reticulum vesicles isolated from rat liver.
AB  - 1. This paper identifies and characterizes an ATP-dependent copper transport
      system in endoplasmic reticulum vesicles isolated from male rat liver. 2. The
      transporter has a Km of 2.5 +/- 1.2 mumol 1(-1) copper glutathione (CuGSH) and a
      Vmax of 4.5 +/- 1.3 nmol (mg protein)-1 (5 min)-1 for copper. 3. At a copper
      concentration of 2 mumol l-1, ATP dependence reaches saturation, with a Km for
      ATP of 4.7 +/- 2.4 mmol l-1 and a Vmax of 2.8 +/- 0.6 nmol (mg protein)-1 (5 min)
      1. 4. The uptake is dependent on ATP hydrolysis, since a low energy analogue of
      ATP, adenosine 5'-[beta-gamma-methylene] triphosphate tetralithium (AMP.PCP), has
      no effect on copper uptake. 5. The transporter is a P-type ATPase, since vanadate
      inhibits uptake with a high degree of specificity (100 mumol l-1 inhibits uptake
      by 50% at a copper concentration of 2 mumol l-1).

PMID- 7738850
TI  - Responsiveness of cat area 17 after monocular inactivation: limitation of
      topographic plasticity in adult cortex.
AB  - 1. Recordings were made from neurones in the splenial sulcus of normal adult cats
      and adult cats which had one eye inactivated by enucleation or photocoagulation
      of the optic disc. Two visually responsive regions were observed, corresponding
      to the peripheral representation of visual area 1 (V1) and the splenial visual
      area. In normal animals, responses to the ipsilateral eye in V1 were restricted
      to the medial half of the splenial sulcus, up to 45-50 deg eccentricity. Thus, by
      inactivating the eye contralateral to the experimental hemisphere, we created a
      region in V1, 1-2 mm wide, that lacked normal inputs. 2. In contrast to results
      from previous experiments where lesions were placed in the central retina,
      neurones in the deprived peripheral representation remained unresponsive to light
      stimuli for up to 12 h after deactivation of the contralateral eye. 3. In animals
      that were allowed to recover from the monocular deactivation for periods of 2
      days to 16 months, there was rearrangement of the retinotopic maps. Receptive
      fields in regions of cortex that normally represented the monocular crescent were
      displaced to the temporal border of the binocular field of vision. However, most
      neurones in the deprived peripheral representation remained unresponsive to
      visual stimuli even more than 1 year after treatment. This is also in marked
      contrast with the extensive reorganization that is observed in the central
      representation of V1 after restricted retinal lesions. Analysis of the cortical
      magnification factor demonstrates that the change in visual topography is local,
      and does not involve an overall centro-peripheral shift of the retinotopic map.
      4. Among the neurones that did show displaced receptive fields, the response
      properties were clearly abnormal. They showed a notable lack of spontaneous
      activity, low firing rates and rapid habituation to repeated stimulation. 5. The
      low potential for reorganization of the monocular sector of V1 demonstrates that
      the capacity for plasticity of mature sensory representations varies with
      location in cortex. Even relatively small pieces of cortex, such as the monocular
      crescent representations, may not reorganize completely if certain conditions are
      not met. These results suggest the existence of natural boundaries that may limit
      the process of reorganization of sensory representations.

PMID- 7738852
TI  - Raphe magnus and reticulospinal actions on primary afferent depolarization of
      group I muscle afferents in the cat.
AB  - 1. In the anaesthetized cat, electrical stimulation of the bulbar reticular
      formation produced a short latency (2.1 +/- 0.3 ms) positive potential in the
      cord dorsum. In contrast, stimulation of the nucleus raphe magnus with strengths
      below 50 microA evoked a slow negative potential with a mean latency of 5.5 +/-
      0.6 ms that persisted after sectioning the contralateral pyramid and was
      abolished by sectioning the ipsilateral dorsolateral funiculus. 2. The field
      potentials evoked by stimulation of the bulbar reticular formation and of the
      nucleus raphe magnus had a different intraspinal distribution, suggesting
      activation of different sets of segmental interneurones. 3. Stimulation of these
      two supraspinal nuclei produced primary afferent depolarization (PAD) in single
      Ib fibres and inhibited the PAD elicited by group I volleys in single Ia fibres.
      The inhibition of the PAD of Ia fibres produced by reticulospinal and raphespinal
      inputs appears to be exerted on different interneurones along the PAD pathway. 4.
      It is concluded that, although reticulospinal and raphespinal pathways have
      similar inhibitory effects on PAD of Ia fibres, and similar excitatory effects on
      the PAD of Ib fibres, their actions are conveyed by partly independent pathways.
      This would allow their separate involvement in the control of posture and
      movement.

PMID- 7738851
TI  - The electrophysiological properties of rat primary afferent neurones with
      carbonic anhydrase activity.
AB  - 1. Intracellular recordings of action potentials (APs) and after
      hyperpolarizations (AHPs) were made from the L3, L4 and L5 dorsal root ganglia
      (DRGs) of 6- to 8-week-old anaesthetized female Wistar rats in vitro at 36.5 +/-
      1 degree C. Neurones were classified by their conduction velocities (CVs) as A
      alpha/beta (> 12 m s-1), A delta (1.3-12 m s-1) or C fibre neurones (< 1.3 m s
      1). 2. Following the recording, fluorescent dye was injected intracellularly.
      Sections of injected neurones were tested for carbonic anhydrase (CA) activity
      histochemically. Reaction product intensity and cell size were measured. Control
      experiments showed that intracellular dye, time in vitro, axotomy and electrical
      stimulation did not affect proportions of CA-positive neurones or their size
      distributions. 3. Approximately 28-30% of DRG neurones were CA positive. Their
      sizes were approximately normally distributed and covered the entire size range
      of DRG neurones with no correlation between size and CA intensity. A greater
      proportion of A alpha/beta cells (62%) than of A delta (32%) or C cells (38%)
      were CA positive, but CA intensity was not correlated with CV. 4. In A neurones
      mean AP duration was significantly shorter in CA-positive cells; for CA-positive
      and CA-negative cells, respectively, these values were 1.6 and 2.8 ms for A delta
      cells; 1.1 and 1.7 ms for A alpha/beta cells; and were 1.2 and 2.3 ms for all A
      cells. CA intensity was negatively correlated with AP duration at base in all
      these groups. 5. Again in A neurones, the mean AHP durations were significantly
      shorter in the CA-positive cells; the mean AHP durations to 80% recovery for
      positive and negative cells were 8.8 and 36 ms, respectively, for A alpha/beta
      cells and were 8.6 and 26 ms, respectively, for all A cells. CA intensity was
      negatively correlated with AHP duration in A alpha/beta cells and all A cells
      together. 6. A fibre cells with the longer AP and AHP durations were all CA
      negative, while cells with the shorter durations included both CA-positive and CA
      negative cells. 7. CA-positive and CA-negative A fibre neurones therefore have
      different electrophysiological characteristics. It is suggested that CA-negative
      A fibre neurones may have slower somatic firing rates and different sensory
      functions from the CA-positive neurones.

PMID- 7738853
TI  - The difference in shape of spontaneous and uniquantal evoked synaptic potentials
      in frog muscle.
AB  - 1. Spontaneous and stimulation-induced uniquantal synaptic activity at the frog
      cutaneous pectoris muscle, treated with neostigmine, was recorded by focal
      extracellular microelectrodes. A monoexponential curve was fitted to the decay of
      each synaptic response. 2. A highly significant positive relationship was found
      between the amplitude and the decay time constant of spontaneous extracellular
      miniature endplate potentials (MEPPs(o)), whereas the relationship displayed by
      evoked uniquantal extracellular endplate potentials (EPPs(o)) was only slightly
      greater than zero. 3. The difference did not stem from changes in the muscle
      membrane conductance or from inclusion of outstanding MEPPs(o) formed as a result
      of the block of acetylcholinesterase. 4. The dependence of the rise time on the
      amplitude was also stronger in MEPPs(o) than in EPPs(o). 5. In the absence of
      neostigmine, MEPPs(o) exhibited a positive correlation between decay time
      constant and amplitude, while EPPs(o) did not show such a correlation. 6. In view
      of previously published models of transmitter release, it is suggested that
      spontaneous secretion of quanta occurs both within and outside the active zones
      facing postsynaptic areas of variable receptor density.

PMID- 7738854
TI  - The effect of partial denervation of developing rats fast muscles on their motor
      unit properties.
AB  - 1. The effects of partial denervation on motor units of the fast twitch extensor
      digitorum longus (EDL) muscle of the rat were studied. 2. Partial denervation was
      performed by surgically removing 2-4 mm of the L4 ventral ramus in 3- and 18-day
      old Wistar rats. Two to three months later, EMG activity, contractile properties
      and muscle fibre types were analysed. 3. After partial denervation the EDL muscle
      became significantly more active, particularly in the animals operated on at 3
      days. The amount of activity during periods of rest was up to 4 times that of the
      control EDL muscle. 4. The maximum tetanic tension developed by the EDL muscles 2
      months after partial denervation at 3 days was only 11 +/- 1.01% (S.E.M., n = 18)
      of the control. In animals operated on at 18 days this value was larger, i.e. 44
      +/- 3.46% (S.E.M., n = 12). The low force output of animals operated on at 3 days
      was also reflected in the low mean motor unit (MU) force output which was only 69
      +/- 5.82% (S.E.M., n = 17) of the contralateral control muscle. In contrast the
      force generated by MUs of rats operated on at 18 days was larger than that of
      control muscles, i.e. 151 +/- 13.05% (S.E.M., n = 11). The number of MUs was 6 +/
      0.32 (S.E.M., n = 19) in rats operated on at 3 days and 12 +/- 0.83 (S.E.M., n =
      14) in rats operated on at 18 days. 5. The speed of contraction decreased and the
      resistance to fatigue increased. These changes were greater in animals operated
      on at 3 days. The proportion of muscle fibres reacting with antibody against slow
      myosin showed a significant increase, especially in the group of animals operated
      on at 3 days.

PMID- 7738855
TI  - Analysis of responses observed in mesenteric microcirculation of the rat during
      systemic hypoxia.
AB  - 1. Direct observations were made of responses to systemic hypoxia (breathing 12
      or 6% O2 for 3 min) evoked in terminal arterioles (TA, 14-30 microns internal
      diameter), precapillary arterioles (PCA, 8-18 microns), collecting venules (CV,
      12-30 microns) and small veins (SV, 20-50 microns) of the mesenteric circulation
      of the anaesthetized rat. Changes in vessel diameter were recorded before and
      after local blockade of alpha-adrenoreceptors with phentolamine when the
      mesentery was covered with Saran Wrap, which is impermeable to O2, and then after
      removal of the Saran Wrap, which would have kept local PO2 relatively high even
      during systemic hypoxia. 2. The majority of TA showed an initial decrease in
      diameter of 14 +/- 1% (mean +/- S.E.M.). These responses were reversed to
      increases in diameter (12 +/- 2%) after phentolamine, but virtually abolished
      after removal of the Saran Wrap (0.3 +/- 2%). 3. Some PCA showed similar
      behaviour to the TA; others showed an increase in diameter (11 +/- 1%). The
      increases in diameter were accentuated after phentolamine (16 +/- 1%), but were
      reduced after removal of the Saran Wrap (6 +/- 2%). 4. CV and SV showed either a
      decrease in diameter followed by relaxation towards control levels, or an
      increase in diameter that waned before hypoxia ceased (6 +/- 1% and 1 +/- 1%,
      respectively). The responses of CV were not altered by phentolamine (8 +/- 1%),
      but SV showed larger increases in diameter (5 +/- 1%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7738856
TI  - Effect of baseline vascular tone on vasomotor responses in cat lip.
AB  - 1. Parasympathetic vasodilator and sympathetic vasoconstrictor responses were
      monitored using laser Doppler measurement of red cell flux in the lips of
      anaesthetized and artificially ventilated cats. 2. Three relationships were
      investigated: (i) that between the reflex parasympathetic vasodilator response
      induced by lingual nerve (LN) stimulation and baseline red cell flux (BRCF)
      levels adjusted by repetitive stimulation of the cervical sympathetic nerve (CSN)
      at various frequencies; (ii) that between the sympathetic vasoconstrictor
      response elicited by CSN stimulation and the adjusted BRCF levels; and (iii) that
      between the vasomotor response evoked by simultaneous stimulation of the LN and
      CSN and the adjusted BRCF levels. 3. The amplitude of the parasympathetic
      vasodilator response increased as BRCF decreased. In contrast, the amplitude of
      the sympathetic vasoconstrictor response increased in line with BRCF. 4.
      Simultaneous activation of the parasympathetic and sympathetic nerves induced a
      blood flow decrease at high BRCF levels but an increase at low levels. 5. The
      tendency for the skin of cold subjects to vasodilate and that of warm ones to
      vasoconstrict in response to various types of stimuli discussed in the light of
      the present findings.

PMID- 7738857
TI  - Baroreceptor influence on the relationships between discharges of different
      sympathetic nerves of the cat.
AB  - 1. The sympathetic nerve discharge (SND) of three different nerves and the
      arterial blood pressure (BP) were recorded simultaneously in baroreceptor-intact
      cats. The linear correlation between different nerve pairs was characterized by
      the coherence spectrum and its baroreceptor-related component was estimated by
      partialization of the coherence on the basis of the blood pressure signal. 2. The
      SND-SND coherence values were higher than those found earlier in baroreceptor
      denervated cats. As shown by partial coherence analysis, in about 50% of the
      experiments with high SND-BP coherence (25 nerve pair recordings), this could be
      explained by superposition of the effects of common central sources of activity
      and of the additional common rhythmic input from the baroreceptors.
      Partialization was ineffective in 50% of the experiments with high SND-BP
      coherence (22 nerve pairs) and also when the SND-BP coherence was relatively low
      (17 nerve pairs). On the group average, after elimination of the components
      explained by baroreceptor influence, the peak SND-SND coherence no longer
      correlated with the SND-BP coherence and both the numerical values and the
      relative pattern of coherences between different nerves became similar to those
      characteristic for baroreceptor-denervated cats. 3. It is suggested that the
      method used in this study represents a 'theoretical barodenervation' and may be
      of great value in experiments, when surgical or chemical denervation of the
      baroreceptors does not represent a real option, e.g. in human subjects.

PMID- 7738858
TI  - Red-green opponent channel mediation of control of human ocular accommodation.
AB  - 1. It has been hypothesized, but not verified empirically, that the control of
      human ocular accommodation is mediated by either the red-green or yellow-blue
      colour channels. Our goal was to determine experimentally whether the red-green
      channel by itself could influence the accommodative response. 2. To find out, we
      isolated the red-green channel through chromatic bandpass filtering and measured
      accommodation under dynamic and static conditions. The effect of this filtering
      was to modulate the red-green channel without disturbing either the yellow-blue
      or luminance channels. 3. Accommodative gain (ratio of response to stimulus
      amplitude) declined monotonically with decreasing bandwidth under dynamic
      conditions. Because the outputs of both the luminance and yellow-blue colour
      channels did not vary with bandwidth, the only explanation is that the red-green
      opponent process was responsible for the effect. 4. Under static conditions,
      however, accommodation was independent of bandwidth. This may be attributable to
      the decreased sensitivity to chromatic contrast that occurs at low temporal
      frequencies.

PMID- 7738859
TI  - Eccentric exercise decreases glucose transporter GLUT4 protein in human skeletal
      muscle.
AB  - 1. Eccentric exercise causes impaired postexercise glycogen resynthesis. To study
      whether changes in muscle concentration of the glucose transporter (GLUT4)
      protein might be involved, seven healthy young men performed one-legged eccentric
      exercise by resisting knee flexion enforced by a motor-driven device. 2. The
      GLUT4 protein concentration in the exercised and in the control thigh was
      unchanged immediately after exercise. On days 1 and 2 after exercise, the GLUT4
      protein concentration in the exercised muscle was 68 +/- 10 and 64 +/- 10% (means
      +/- S.E.M.; P < 0.05), respectively, of the concentration in the control muscle,
      and had returned to control values on days 4 and 7. 3. The muscle glycogen
      concentration decreased from 404 +/- 44 to 336 +/- 44 mmol (kg dry wt)-1 (P <
      0.05) during exercise. The glycogen concentration remained significantly lower
      than in the control thigh on days 1 and 2 after exercise but on days 4 and 7 no
      differences were found. 4. Although no cause-effect relationship was established,
      these findings may suggest that decreased muscle concentrations of GLUT4 protein,
      and, hence, a decreased rate of glucose transport into muscle cells, may be
      involved in the sustained low glycogen concentration seen after eccentric
      exercise.

PMID- 7738860
TI  - Imagination of dynamic exercise produced ventilatory responses which were more
      apparent in competitive sportsmen.
AB  - 1. The cardiorespiratory response to imagination of previously performed
      treadmill exercise was measured in six competitive sportsmen and six non-athletic
      males. This was compared with the response to a control task (imaging letters)
      and a task not involving imagination ('treadmill sound only'). 2. In athletes,
      imagined exercise produced increases in ventilation which varied within and
      between subjects. The mean maximal increase (11.71 min-1) was approximately 20%
      of the ventilatory response to actual exercise. This was primarily due to
      treadmill speed-related increases in respiratory frequency (mean maximal
      increase, 14.8 breaths min-1) and resulted in significant reductions in end-tidal
      PCO2 (mean maximal fall, 7 mmHg). These effects were greater (P < 0.01) than any
      observed during the control tasks. 3. Changes in heart rate (mean increase, 12
      beats min-1) were not significantly different from those observed during the
      control tasks (P > 0.2). 4. In non-athletes, imagination of exercise produced no
      changes in cardiorespiratory variables. No significant differences were detected
      in subjective assessments of movement imagery ability between athletes and non
      athletes (P = 0.17). 5. This study demonstrates that ventilatory effects, when
      observed, are specific to imagination of exercise. The greater likelihood of
      generating ventilatory responses in highly trained athletes, experienced in
      'rhythmic' sports, may be related to awareness of breathing and its role in
      exercise imagination strategy. A volitional component of the response cannot be
      discounted.

PMID- 7738861
TI  - [Rapid drug-administration method using caged chemical compounds].

PMID- 7738862
TI  - [Movement-related potentials associated with motor inhibition during different
      types of stop signal paradigm in humans].
AB  - The motor inhibition process was examined in humans by monitoring reaction times,
      electromiograms, and movement-related potentials. Four subjects performed two
      types of visual stop signal paradigm. In one type, they were required to push a
      button (GO) or not to push it (NOGO), in another type, to release the button (GO)
      or to keep pushing it (NOGO). The results were summarized as follows; (1) The EEG
      waveform pattern was remarkably consistent among subjects. NO-GO-specific
      negative-positive potentials were observed under both tasks without significant
      background EMG activity changes in agonist and antagonist muscles. (2) The timing
      of the onset and the peak latency of the negative potential relative to the
      second stimulus, S 2, were constant (about 180-200 ms and 230-250 ms for each) in
      both tasks. The time interval between the initial onset of the negative potential
      and its peak latency was also constant (about 50 ms) in both tasks. The amplitude
      of the negative potentials was maximum at FCz (supposed to be around
      supplementary motor area) and their distribution was invariant among tasks.
      Constant features of NO-GO-specific potentials during both task performance
      suggested the temporally and spatially same inhibition process might specifically
      suppress the new motor program regardless of the existence of ongoing motor
      program.

PMID- 7738863
TI  - Saluting courage.

PMID- 7738864
TI  - Support of nursing theories.

PMID- 7738865
TI  - Treatment of inpatients with bipolar disorders: a role for self-management
      groups.
AB  - 1. Group therapy for outpatients with bipolar disorders is perceived as an
      effective adjunct to psychopharmacotherapy. Although medications to treat bipolar
      disorders have been well characterized and compliance usually results in good
      control of symptoms, the value of a group intervention program focusing on self
      management has been ignored in inpatient treatment. 2. A patient workbook is
      being planned. This workbook is intended to impart additional information
      concerning self-management and free the therapist from devoting group time to
      individual didactic instruction. 3. Inpatients with bipolar disorders have
      responded favorably to diagnostically homogeneous group therapy. The data
      accumulated from their reports helped to formulate the Self-Management of Bipolar
      Disorder Group Model and this new model must be compared with the original model
      to ascertain effectiveness.

PMID- 7738866
TI  - Partner abuse against female nursing students.
AB  - Although nurses may have the necessary skills to plan care of clients in a
      variety of settings, experience and research demonstrate that nursing
      interventions with women victims of violence have been consistently inadequate.
      Of the 243 nursing students included in this study, 8% reported experiencing
      physical abuse, and 18.9% reported experiencing nonphysical abuse. Difficulties
      with depression for 26.1% of the students and some level of clinical stress were
      reported in over half of the group. Specific needs to combat violence and abuse
      against nurses and nursing students include providing better information on such
      behavior by incorporating family-violence education into nursing-school
      curricula, and using this proactively in confronting domestic violence in home
      and work settings.

PMID- 7738867
TI  - Linking hospital and community.
AB  - A thorough crisis evaluation requires understanding of the client's premorbid
      personality, support systems, previous episodes of decompensation, past
      treatments, and the interaction of a precipitant with a particular personality
      structure. The key to a successful treatment model is the proper treatment of the
      client in his or her community. Thus, the development of adequate linkages within
      the system to support this effort becomes imperative. By utilizing problem
      solving approaches and anticipatory planning, the Psychiatric Emergency Service
      is instrumental in achieving maximum positive outcomes through contact with the
      patient and multiple systems.

PMID- 7738868
TI  - Values, ideologies, and dilemmas: professional and occupational contradictions.
AB  - Developments in many "for-profit" psychiatric hospitals over the past decade
      raise concerns about the nature of values in proprietary health care. These
      developments raise questions of whether nursing values and ideologies can coexist
      with those of the current health care environment. There are two influences that
      are important in considering the issue of nursing within the for-profit context:
      the commercial motivation of the present health care system and the possible
      subordination of nursing values to the objectives of lay (business) persons. It
      is imperative to initiate dialogues of the problematic ideological and ethical
      dilemmas confronting nurses in the work setting.

PMID- 7738869
TI  - Dementia-related behaviors in Alzheimer's disease and AIDS.
AB  - In both Alzheimer's disease (AD) and AIDS, family members vary in their
      perceptions of the individual's ability to control his or her cognitive or
      behavioral functioning. Family members who believe that the behaviors are
      unintentional generally experience less distress than do family members who
      believe that the individual has control over his or her thoughts or behaviors.
      The manifestations of intellectual and cognitive dysfunction of AD and AIDS are
      strikingly similar. Impairments of memory, concentration, and abstract thinking;
      confusion and disorientation; and slowed mental capacities are among the shared
      symptomatology, and may eventually become the catalysts for family caregiving. It
      is imperative that clinicians and researchers collaborate in further
      investigation in order to ease the burden on family caregivers and facilitate
      adaptations of caregiving methods.

PMID- 7738870
TI  - Therapeutic management of helping boundaries.
AB  - A therapeutic nurse-patient relationship is based upon the effective management
      of professional practice boundaries. Boundary violations may be difficult to
      detect and manage because they often are subtle and driven by one's own needs.
      Early detection and response is critical to preventing boundary relaxation and
      violation. Self-assessment is an important aspect of boundary management.
      Identification of vulnerability to boundary violation may assist the nurse in
      determining the need for supervision or consultation.

PMID- 7738871
TI  - Geriatric mental health interventions in the home.
AB  - Geriatric mental health treatment should be considered an integral part of the
      services provided by home health care agencies or community mental health
      centers. Public policy is needed to cover in-home psychiatric services to
      caregivers and elders, one way to respond effectively to their needs. This policy
      should include the provision of adequate numbers of geriatric mental health
      specialists who are specifically trained for work with the aged in their homes.

PMID- 7738872
TI  - Venlafaxine: a novel antidepressant.
AB  - More and more antidepressants are being used to treat depression that do not meet
      DSM-IV criteria for major depression. Venlafaxine is one alternative among many
      pharmacologic agents. Studies suggest it provides as good a response as other
      antidepressants, is less cardiotoxic, and produces fewer anticholinergic and
      sedative side effects.

PMID- 7738873
TI  - Reporting on reports--cardiological intervention in elderly patients.
AB  - We asked consultant cardiologists and geriatricians in the Trent Region to assess
      the change in attitude towards cardiological investigations in the elderly over
      the last five years. We then reviewed data from three cardiothoracic centres to
      see if this change was reflected in the number of invasive cardiological
      procedures performed. The consultants' opinion that more elderly patients are
      being referred for and receiving more investigations and treatment was reflected
      in a disproportionate increase in cardiac catheterisations and revascularisation
      procedures in the elderly between 1990 and 1993. There is little to suggest that
      these changes came about as the result of the College report on cardiological
      intervention in elderly patients.

PMID- 7738874
TI  - Management of heart disease in the elderly in the Plymouth Health District.
AB  - In the light of a report from the Royal College of Physicians, the management of
      heart disease in the elderly (> 70 years) was studied in the Plymouth Health
      District in 1992. A survey of general practitioners was undertaken to assess how
      they would handle particular aspects of heart disease in their elderly patients.
      The admissions of older patients to the coronary care unit following an acute
      myocardial infarction and their outcome were detailed. The numbers of non
      invasive cardiological investigations undertaken in the elderly were monitored,
      as were the referral rates to a cardiology outpatient clinic. The overall
      conclusion is that physicians and general practitioners alike view coronary
      artery disease as a medical condition with little consideration of the surgical
      option, despite good evidence that elderly patients often do very well following
      coronary artery bypass grafting. Future resource planning should address the
      problem of an overburdened cardiac surgery service.

PMID- 7738875
TI  - Cardiopulmonary resuscitation: doctors and nurses expect too much.
AB  - Doctors and nurses in the UK and US have an over-optimistic view of patients'
      chances of surviving an attempt at cardiopulmonary resuscitation (CPR). If
      medical staff are to follow the recommendation that they should discuss the pros
      and cons of CPR with patients and their relatives, they should at least be able
      to give them realistic expectations of survival; otherwise inappropriate
      decisions may be made. Resuscitation training programmes should routinely include
      data on survival from CPR in differing circumstances.

PMID- 7738876
TI  - Quality in the dermatological contract. A report from the Workshop on Quality
      Issues in Dermatological contracting of the British Association of
      Dermatologists.
AB  - This document is a summary of the most important points from a meeting convened
      by the audit sub-committee of the British Association of Dermatologists (BAD) and
      the research unit of the Royal College of Physicians on 16 May 1994. Participants
      represented the views of district general and teaching hospital dermatologists, a
      fundholding general practitioner, a health commissioning agent and patient
      support groups. The meeting was preceded by a workshop on 6 April 1994, involving
      16 patient support groups chaired by Consumers Association from which a
      discussion paper was presented by two representatives. This report is intended
      for dermatologists, contract managers and purchasers.

PMID- 7738877
TI  - Complex interactions of hepatitis B virus with its host and environment. The
      Croonian Lecture 1994.

PMID- 7738878
TI  - Pharmacovigilance: paradise lost, regained or postponed? The William Withering
      Lecture 1994.

PMID- 7738879
TI  - Editor emeritus: Robert F Mahler.

PMID- 7738880
TI  - Limitations of expert evidence.
AB  - Doctors from diverse specialties are required, from time to time, to give
      evidence either in documentary form or in person to both civil and criminal
      courts. A joint conference of the Royal Colleges of Physicians and Pathologists
      was held at the Royal College of Physicians on 25 October 1994, with the
      intention to explore those areas where difficulties might arise for the doctor
      from either a medical or a legal point of view, both as an informative exercise
      and in order to identify subjects which might usefully be further examined.

PMID- 7738881
TI  - Assessing and counselling trainees.
AB  - Increasing attention to the training of junior doctors and the changes in career
      structure outlined in the Calman Report make effective assessment and counselling
      of trainees in medicine essential. A conference held at the Royal College of
      Physicians on 5 October 1994 considered some of the problems and practicalities
      of incorporating such developments into new training programmes.

PMID- 7738882
TI  - Russian nursing in the Crimean war.
AB  - Although the practice of military medicine and surgery goes back to antiquity,
      the British date the proper care of the wounded from the arrival of Florence
      Nightingale at Scutari in Turkey on 4 November 1854. The 140th anniversary of her
      work in that winter of the Crimean war is being celebrated by an exhibition at
      the Florence Nightingale Museum, 2 Lambeth Palace Road SE1 7EW, from 1 December
      1994 till 30 April 1995. For the first time in this country it will tell a little
      of the other side of the story--the exploits of Russian nurses in caring for the
      casualties from both sides in the conflict--which is the subject of this article.

PMID- 7738883
TI  - Clinical research in the year 2000.

PMID- 7738884
TI  - Economics and incomplete case for public support for research.

PMID- 7738885
TI  - More general physicians or specialists?

PMID- 7738886
TI  - Cardiological services for the elderly.

PMID- 7738887
TI  - Blood use for surgical patients: a study of Scottish hospital transfusion
      practices.
AB  - The use of an effective schedule for ordering blood for transfusion for surgical
      patients is the accepted standard of practice for hospital blood banks in UK
      hospitals. The use of maximum surgical blood ordering schedules (MSBOS) was
      surveyed throughout Scotland in 1992 and 1993. Twenty-seven hospitals
      participated in the study. Twenty-three (85%) of these 27 operated a schedule.
      Schedules varied between hospitals both in the way the schedules were implemented
      and in the amount of blood allocated to operations. The implementation of
      schedules was compared in three hospitals each for Caesarean section,
      transurethral resection of the prostate (TURP) and primary hip replacements.
      Adherence to the schedules averaged 76% (range 10-100%) and varied with
      operation, tariff, and hospitals. Blood use per operation did not depend on the
      amount of blood allowed by the schedule. Use of a MSBOS does not appear to
      influence clinical use of blood for transfusion, indicating that the gains in
      efficient use of laboratory resources and in safe handling of blood units can be
      made without compromising patient care.

PMID- 7738888
TI  - Seasonal variation in the incidence of ruptured abdominal aortic aneurysm.
AB  - In order to determine any possible influence of climatic variables on the
      incidence of abdominal aortic aneurysm rupture, we reviewed 49,144 autopsies
      performed in two major hospitals in Rome, Italy, from January 1956 to March 1986.
      There were 297 subjects who were found to be sufferers of atherosclerotic
      abdominal aortic aneurysm for a prevalence of 0.6%. The aneurysm was intact in
      220 cases (74%) and ruptured in 77 cases (26%). The highest incidence of ruptured
      aneurysm occurred during the Autumn and in the months May and July. The incidence
      of ruptured aneurysm was highest in case of significant changes of the
      atmospheric temperature. There was no correlation between the incidence of
      ruptured aneurysm and barometric pressure or humidity.

PMID- 7738889
TI  - Assessment of the common bile duct before cholecystectomy: a direct comparison
      between ultrasonography and intravenous cholangiography.
AB  - Sixty-seven consecutive patients undergoing cholecystectomy for symptomatic
      gallstones were investigated by both ultrasonography (US) and intravenous
      cholangiography (IVC). This provided the opportunity to compare these methods for
      assessing the common bile duct (CBD) preoperatively for stones. The results were
      correlated with a subsequent definitive procedure that formed the diagnostic
      standard in each case. The CBD diameters of 8 (12%) patients with stones was
      significantly greater than those without stones (t = 10.96, P < 0.001).
      Sensitivities of US and IVC were 87.5% and 100% respectively, but there were
      three unsuccessful IVC investigations that had to be excluded from the
      calculations. Specificities and overall accuracy of both methods were greater
      than 95%. The positive and negative predictive value of each test was similar and
      no difference using McNemar's test was found between US and IVC for providing
      information relating to CBD stones. Performing both procedures as routine
      assessment of the CBD is thus unnecessary as US, in conjunction with clinical
      history and liver biochemistry profile, provide an adequate preoperative screen
      of the CBD.

PMID- 7738890
TI  - Laparoscopic subtotal cholecystectomy.
AB  - Laparoscopic subtotal cholecystectomy has been carried out on 5 patients during a
      28-month period. The indications were severe inflammation/fibrosis in 3 patients,
      cirrhosis with mild portal hypertension in 1 patient and the Mirizzi syndrome in
      the last patient. There were no deaths and only minor in hospital morbidity.
      Subtotal cholecystectomy carried out laparoscopically is a safe procedure and can
      be used in selected patients in order to avoid conversion to an open operation.

PMID- 7738891
TI  - Video-thoracoscopic lung biopsy in diagnosis of interstitial lung disease.
AB  - Lung biopsy remains an important investigation in the diagnosis of diffuse
      interstitial lung disease despite improved diagnostic yield of high resolution
      computed tomography scanning. We describe 19 pulmonary wedge biopsies (13 men and
      6 women) performed using videothoracoscopic technique. The median age of the
      patients was 56 years (range 32-72 years). All our patients were suspected to
      have diffuse interstitial lung disease and were referred for lung biopsy to
      obtain a histological diagnosis. Thoracoscopic wedge excisions were accomplished
      under general anaesthesia using high frequency jet ventilation and a percutaneous
      stapling device. A tissue diagnosis was obtained in all patients: 8 had
      cryptogenic fibrosing alveolitis, 3 had interstitial pulmonary fibrosis, 2 had
      emphysema, 2 had extrinsic allergic alveolitis, 2 had sarcoidosis, 1 had non
      specific chronic inflammation, and 1 had pulmonary haemosiderosis. There were no
      operative deaths. There was one failure resulting in conversion to an open
      procedure. There were three complications: two air leaks and one effusion. Median
      postoperative hospital stay was 2 days (range 2-7 days). We conclude that
      videothoracoscopic wedge biopsy is a safe and effective procedure and should be
      recommended in patients who require a histological diagnosis of diffuse
      interstitial lung disease.

PMID- 7738892
TI  - Breast abscesses in Nigeria: lactational versus non-lactational.
AB  - This review of 299 cases of breast abscesses seen over a 10-year period (1981
      1990) at the University of Calabar Teaching Hospital in Nigeria seeks to
      establish the current status of breast abscesses in the tropics. Lactational
      breast abscess constitutes 95% of breast abscesses while non-lactational breast
      abscess constitutes only 5% in this review. The commonest pathogen cultured from
      lactational breast abscess is Staphylococcus aureus and the disease responds to
      incision and drainage and systemic antibiotics, while non-lactational breast
      abscess is caused mostly by anaerobic organisms, usually with underlying mammary
      duct ectasia. The low incidence of non-lactational breast abscess corresponds to
      the low incidence of cigarette smoking and mammary duct ectasia in Nigerian
      women. While the high incidence of lactational breast abscess corresponds to the
      high rate of breast feeding and low level of personal hygiene in the low income
      group Nigerian women in which the disease is commonest. Economic recession has
      also reduced patronage of artificial feeds thus intensifying breast feeding and
      consequent lactational breast abscess.

PMID- 7738893
TI  - Exploration of the common bile duct for stones: the influence of the flexible
      choledochoscope and perioperative antibiotic prophylaxis.
AB  - A retrospective study of 110 patients, out of a total of 743 open
      cholecystectomies, who have undergone common bile duct (CBD) exploration for
      stones between 1985 and 1990. CBD exploration was performed in the presence of
      abnormal peroperative cholangiogram in 86 (78%) patients. The remaining 24
      patients were known to have either an abnormal preoperative ERCP or palpable
      ductal stones at the time of surgery. Post exploratory choledochoscopy was
      performed as an additional completion procedure in 58 (53%) patients and it
      identified further stones in 28 (48.3%) of these patients. There were three
      patients in whom no stones were identified on exploration of the CBD. Documented
      evidence of peroperative antibiotic prophylaxis was obtained in 78 (71%)
      patients. A total of 27 (24.5%) patients developed complications including seven
      (6.4%) patients with retained stones. In four of these patients with retained
      stones, flexible choledochoscopy was undertaken as an additional completion
      procedure to ensure ductal clearance. Cardiorespiratory and septic complications
      were the next most common problems occurring in 6.5% and 5.4% respectively, of
      patients reviewed. In conclusion, the retained stone rate has fallen from 14% in
      1987 to 6.4% in this study. The choledochoscope has influenced this as it
      identified further residual stones following conventional exploration. The sepsis
      rate has also fallen from 19.5% to 4.5% in this study. We believe this is due to
      the use of antibiotic prophylaxis.

PMID- 7738894
TI  - Experience of an implantable central venous access system in a district general
      hospital.
AB  - Reliable access to a central vein is increasingly important in the treatment of
      major acute and chronic disease. The use of an implantable central venous access
      device in a district general hospital is reviewed. Fifty-four PortaCaths (Kabi
      Pharmacia, Milton Keynes, UK) were inserted in 51 patients over a 7-year period.
      Most patients had haematological disease, often with neutropenia and
      thrombocytopenia. There were a total of 22,515 catheter days experience. Twelve
      catheters were removed for complications with an overall complication rate of
      0.93/1000 catheter days. There were four line infections and four episodes of
      periport sepsis. Occasional catheter thrombosis was usually cleared with
      urokinase. Neutropenic and immunocompromised patients had an increased
      complication rate. PortaCaths were well tolerated by patients and required
      minimum maintenance. An implantable central venous access device proved safe and
      reliable for use in a district general hospital.

PMID- 7738895
TI  - A safe technique of major mammary duct excision.
AB  - The classical Hadfield's operation for duct ectasia/periductal mastitis results
      in nipple anaesthesia in most women and nipple/areola necrosis in some patients.
      To obviate these two complications we have modified the technique of major duct
      excision. The incision is given over only one-third of areolar circumference and
      no areolar flap is raised. In the 17 women treated by this technique the cosmetic
      results were good in all of them with no nipple/areola necrosis. The nipple
      sensation was preserved in all cases. There was only one case of recurrence of
      nipple discharge. The technique offers a safer alternative to the classical
      Hadfield's operation.

PMID- 7738896
TI  - Effects of plane mechanical forces in wound healing in humans.
AB  - The effects of the application of external forces acting in the plane of the skin
      on early scars during healing were investigated. A simple apparatus was developed
      for this purpose. The scars were followed up for a minimum of 12 months
      postoperatively and all settled well.

PMID- 7738897
TI  - Longterm follow-up of biliary stents for retained common bile duct stones in
      elderly patients.
AB  - Common bile duct (CBD) stones in elderly patients are best treated by endoscopic
      sphincterotomy (ES). If CBD clearance cannot be achieved endoscopically a biliary
      stent may be inserted. Although satisfactory short-term results have been
      reported, few reports on their longterm outcome are available. Over a 3-year
      period, January 1987 to December 1989, 100 patients with CBD stones were referred
      for endoscopic stone removal. In 14 of these patients (3 men, 11 women; median
      age 83 years, range 79-97 years) the CBD could not be cleared endoscopically and
      a stent was inserted. Twelve of the 14 patients were jaundiced and 5 had acute
      cholangitis (AC). The maximum diameter of the retained stones ranged from 10-42
      mm with a median of 17 mm. Stent insertion resolved jaundice and sepsis in all
      cases and all patients were discharged from hospital. In-patient stay ranged from
      1-82 days (median 12 days) and was significantly increased by the presence of
      acute cholangitis (P = 0.03, Mann-Whitney U-test). Longterm follow-up was
      obtained in 13 of the 14 patients (93%) by referral to their general practitioner
      and out-patient notes. Seven patients are alive and well (median follow-up 43
      months, range 34-60 months). One of these 7 developed further jaundice owing to
      stent migration and had further ES and stone removal. Six patients died at 1, 3,
      12, 32, 36 and 42 months following stent insertion from unrelated causes. One
      patient developed further AC requiring antibiotic treatment and another patient
      required stent replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738898
TI  - Shorter stay urology: the way forward.
AB  - A large part of the total cost of the treatment of surgical patients in hospitals
      is from the duration of hospitalization. Urology is well suited for short-stay
      surgery, and a large proportion of our work is elective in nature. We audited our
      in-patients over a 6-month period and found that 77% of our patients stayed for 3
      days or fewer. The advantages of having elective 5-day beds in maintaining our
      throughput without requiring an increase in the total number of beds is
      discussed.

PMID- 7738899
TI  - Visual handicap in south-east Scotland.
AB  - A study of 288 cases was made of those registered blind and partially sighted
      patients in Lothian Health Board area. The purpose of this study was to identify
      the trend of the main cause of visual handicap in a general population. The
      registration rates were analysed by age, sex and causes. It was found that the
      leading causes for blindness were age-related macular degeneration (ARMD)
      (58.8%), chronic open angle glaucoma (COAG) (12.8%), proliferative diabetic
      retinopathy (PDR) (4.9%), while for partial sight (PS) the main causes were age
      related macular degeneration (ARMD) (57.1%), chronic open angle glaucoma (COAG)
      (8.8%) and congenital (4.7%). For both men and women the incidence rate of
      blindness remains low until the age of 65, followed by a considerable increase,
      especially after the age of 75. The male to female ratio for blindness was 1:2.06
      and for partial sight 1:2.58.

PMID- 7738900
TI  - Which surgeons in a district general hospital should treat patients with
      carcinoma of the rectum?
AB  - There has recently been considerable media and medical interest in the apparent
      differences of the results of the surgical treatment of colorectal cancer by
      specialist and non-specialist colorectal surgeons. We have therefore audited and
      compared the results of the elective treatment of cancers of the rectum and
      distal sigmoid colon undertaken by two surgeons working in the same hospital, one
      a general surgeon with a vascular special interest and the other a colorectal
      specialist. Although our results demonstrate no difference in overall survival,
      the higher clinical leak rate and higher rate of palliative diversional surgery
      in the general surgeon's group lends some support to the argument that carcinoma
      of the rectum should be treated by surgeons with a special interest in colorectal
      surgery.

PMID- 7738901
TI  - Crossover trial of partial shift working and a one in six rota system for house
      surgeons in two teaching hospitals.
AB  - The objective of this study was to compare an on call rota and partial shift
      working pattern for house surgeons in two hospitals. The study was conducted
      using a crossover trial of working both systems for 6 weeks each in two groups of
      newly appointed house surgeons. Assessment was by questionnaire to house
      surgeons, consultants, registrars, nursing staff and patients. The study took
      place at the departments of general surgery at Guy's and Lewisham Hospitals,
      London. A total of 12 house surgeons attached to four surgical firms and their
      consultants and registrars were the subject of our study. In addition the
      permanent nursing staff on designated general surgical wards and those patients
      of greater than 48 h stay on those wards on the day of assessment took part.
      Expectations of reduced fatigue levels using the partial shift system were not
      fulfilled. In contrast, this working pattern led to perceived disruption of the
      running of the surgical firms and demoralization of the house surgeons. Standards
      of patient care were, however, equally high using a rota or partial shift system.
      This comparison of a partial shift working pattern to an on call rota of similar
      average weekly hours demonstrated a marked preference for an on call rota from
      both medical and nursing staff although patients found both systems acceptable.

PMID- 7738902
TI  - Excision of the germinal matrix: a modification.

PMID- 7738903
TI  - Ligation of the thoracic duct without thoracotomy for the treatment of
      postoperative chylothorax: a newly designed surgical procedure.
AB  - A newly designed surgical procedure of ligation of the thoracic duct without
      thoracotomy for the treatment of postoperative chylothorax is presented. A case
      of chylothorax following resection of carcinoma of the oesophagus was treated
      successfully with ligation of the thoracic duct without thoracotomy. Its
      advantages were very prominent consisting of maintenance of the integrity of the
      thorax, less traumatization, no need of a drainage tube and shorter
      hospitalization, much easier to expose the thoracic duct than the conventional
      transthoracic approach. We can find no similar report in any published
      literature.

PMID- 7738904
TI  - Clubfoot: congenital talipes equinovarus.
AB  - Congenital talipes equinovarus (ctev) occurs in approximately 1.2 per thousand
      live births in the UK. The prevalence is less in Orientals (0.6 per thousand),
      and higher in Hawaiians (6.8 per thousand) and in East Africans. The aetiology is
      still obscure, but Ruth Wynne-Davies' view has yet to be challenged, that there
      is a genetic component with an environmental trigger. There is no recognisable
      pattern of inheritance, but if one child in a family is affected, the risk that a
      second will have ctev is 1 in 35.

PMID- 7738905
TI  - The Bateman bipolar prosthesis: a prospective study in primary osteoarthritis.
AB  - We present a prospective study of Bateman bipolar prosthesis performed over 5
      years in Perth. All patients were treated for primary osteoarthritis using a
      cementless straight Moore stem and the bipolar acetabular component. Assessment
      was made at 6-monthly intervals. Harris hip scores were calculated and
      radiological parameters of inner bearing movement, component migration and
      proximal osteoporosis were assessed. The group comprised 76 prostheses in 72
      patients. The mean Harris hip score at 3 years follow-up was 85, however with a
      wide range between 55 and 99. A total of 30% of patients at 3 years follow-up had
      a Harris hip score at less than 70. Twenty-seven per cent of the prostheses at 3
      years had restriction of movement at the inner bearing and 43% were judged to
      have moderate or severe stress shielding around the proximal femur. The clinical
      results were unpredictable with thigh pain being a significant problem. Because
      of the unpredictable results we would not advocate the use of the Bateman
      prosthesis in primary osteoarthritis.

PMID- 7738906
TI  - Detection and localization of interleukin-8 mRNA and protein in human placenta
      and decidual tissues.
AB  - It has been reported that interleukin-8 (IL-8) is secreted from the placental and
      decidual tissues and that IL-8 levels in the amniotic fluids are significantly
      elevated by chorioamnionitis or labor pain. The present study was aimed at
      defining the localization of IL-8 mRNA as well as IL-8 protein at the feto
      maternal interface using in situ hybridization and immunohistochemical staining.
      Both IL-8 mRNA and protein were localized in cytotrophoblast, syncytiotrophoblast
      and Hofbauer cells of the placenta, decidual stromal cells, decidual lymphocytes
      and endometrial gland cells. IL-8 secretion from glandular cells has not
      previously been reported. In addition, we confirmed IL-8 mRNA expression and
      secretion of IL-8 by an endometrial cancer cell line (Ishikawa) using the reverse
      transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent
      assay (ELISA) methods, respectively.

PMID- 7738907
TI  - Generation of an antibody to HLA-G in transgenic mice and demonstration of the
      tissue reactivity of this antibody.
AB  - A method was devised to generate antibodies against the non-classical class I HLA
      G antigen. This consisted of immunising HLA-A2/beta 2m double transgenic mice
      with HLA-G transfected into mouse Ltk- cells. A polyclonal antibody was obtained
      which appears to be specific for HLA-G. The staining pattern of this antibody was
      restricted solely to all populations of extravillous trophoblast. No fetal
      tissues reacted with this antibody, including those where HLA-G mRNA has been
      demonstrated, such as fetal eye, thymus and liver. This study confirms that HLA-G
      is a trophoblast-specific protein, although it remains a possibility that the
      technique of immunohistology is not sufficiently sensitive to detect low level
      HLA-G antigen expression in non-trophoblast tissues.

PMID- 7738908
TI  - The effect of pentoxifylline on in-vitro fertilization in the presence of anti
      sperm antibodies.
AB  - In cases of severe immunological male-factor infertility, impairment of
      spermatozoal motility and of acrosome reaction resulting in reduced fertilization
      capacity have been described by several authors. The present study investigated
      the use of pentoxifylline in enhancing in-vitro fertilization (IVF) in the
      presence of anti-sperm antibodies. Thirty-seven IVF cycles were conducted in 28
      different couples suffering from immunological male-factor infertility with at
      least 50% antibody-coated spermatozoa. Sibling oocytes were inseminated at random
      with spermatozoa incubated with or without 3.6 mM pentoxifylline after selection
      by a Percoll gradient. No difference in motility of the final sperm preparations
      was observed prior to insemination. Fertilization rate, cleavage rate and embryo
      quality were similar in both treatment and control groups. Nine out of ten
      pregnancies were achieved after the replacement of embryos both from the
      treatment and control group. Although pentoxifylline is known to enhance motility
      in-vitro and to promote induced acrosomal loss, its indiscriminate use failed to
      improve IVF performance in patients with anti-sperm antibodies. Further research
      may be necessary in order to elucidate whether a given subpopulation of these
      patients may benefit from a selective application of pentoxifylline.

PMID- 7738909
TI  - Cystic fibrosis and congenital agenesis of the vas deferens, antisperm antibodies
      and CF-genotype.
AB  - Antisperm antibodies are formed as a result of vasal and epididymal obstruction.
      Fourteen males of different ages (pre-, peri- and post-pubertal) with bilateral
      congenital vasal agenesis and epididymal obstruction secondary to cystic fibrosis
      (CF), and seven men with congenital bilateral aplasia of the vas deferens (CBAVD)
      were evaluated with regard to both the presence and levels of serum antisperm
      antibodies, and the CF-genotype. While IgA and IgG were not detected among pre-
      and peri-pubertal CF patients, 4 out of 10 (40%) exhibited IgM binding to sperm
      tail-tip. Post-pubertal CF patients showed high antisperm antibody (ASA) levels
      in 3 of the 4 males (75%) evaluated for the three isotypes assayed. ASA were
      found in 5 of 7 CBAVD patients (71%); IgG (n = 3) and IgM (n = 4) were found to
      be the predominant isotypes bound to sperm tail-tip. CF-genotype analysis
      revealed two pre-pubertal patients with the DeltaF508/DeltaF508 CF-genotype and a
      positive ASA response, thus suggesting an earlier or more severe blockage. In
      addition, the two CBAVD patients found to have a ?/? CF-genotype on the initial
      screening did not have ASA. The altered antigenicity of sperm associated with
      initiation of spermatogenesis appears to modify the antisperm antibody isotypes.
      Further studies on a larger number of patients may allow for a better
      understanding of the ASA response, as well as a better understanding of a
      possible phenotype/genotype association between the CF-genotype and the
      immunologic response.

PMID- 7738910
TI  - Prostaglandin F2 alpha immunization of prepubertal beef heifers: effects of
      conjugate dose and timing of immunization relative to puberty on the onset of
      puberty and subsequent ovarian function.
AB  - Fifty-six prepubertal Hereford cross Friesian heifers were assigned to seven
      treatment groups: (1) primary (day 0) and booster (day 41) using 10 mg human
      serum albumin (HSA) (control); (2) primary and booster (day 41) immunizations
      using 3.3 mg prostaglandin F2 alpha PGF-HSA conjugate; (3) primary and booster
      (day 83) using 3.3 mg PGF-HSA; (4) primary and booster (day 210) using 3.3 mg PGF
      HSA; (5-7) as in treatments 2-4 except 10 mg PGF-HSA were used. Plasma
      progesterone concentrations were used to determine the onset of puberty and the
      presence of a corpus luteum (CL); plasma PGF antibody titres were determined at
      28-day intervals. There was no effect (P > 0.05) of conjugate dose or booster
      interval on mean antibody titres and there was no interaction between them.
      However, heifers in the 83- and 210-day booster treatments had higher (P < 0.05)
      peak antibody titres than heifers in the 42-day booster treatments. Puberty was
      delayed in 40% (16/40) of PGF-immunized heifers and 40% (16/40) of heifers formed
      persistent CL after puberty. Overall, eight of the heifers with delayed puberty
      also formed a persistent CL. There was a positive correlation between mean titre
      and onset of puberty but not with duration of persistent CL.

PMID- 7738911
TI  - Immunoreactivity with native zona pellucida of antibodies against a 19 amino acid
      synthetic peptide corresponding to human ZP3.
AB  - Immunization of female Syrian hamsters with a 19mer-synthetic peptide
      corresponding to amino acid sequence 323-341 of human ZP3 and coupled to
      diphtheria toxoid (DT) led to generation of antibodies against both the peptide
      as well as DT. Antisera showed positive reaction in ELISA with solubilized
      isolated zona pellucida (SIZP) from human oocytes. In an indirect
      immunofluorescence assay, the anti-peptide antibodies bound to zona pellucida of
      human and bonnet monkey but failed to recognize that of mouse, rabbit, hamster
      and dog. These studies will help in designing a synthetic peptide based ZP
      immunocontraceptive vaccine for human application.

PMID- 7738912
TI  - IgG asymmetric anti-ovalbumin antibodies synthesized by virgin and pregnant rats.
AB  - A study on the synthesis of asymmetrical IgG molecules 'with no specific
      activity' and with anti-ovalbumin activity was carried out both in virgin rats
      and in rats inoculated with ovalbumin and made pregnant by syngeneic and
      allogeneic males. Before pregnancy, female rats synthesize about 23% of
      asymmetrical IgG molecules, when the level of these molecules is assessed in
      total IgG, in anti-ovalbumin IgG and in the supernatant from the adsorption of
      anti-ovalbumin antibodies. On the other hand, anti-ovalbumin antibodies isolated
      are predominantly of the symmetrical IgG type; they are also precipitants and
      effectors of the biological mechanisms that the host operates to preserve
      pathogenic antigens (bacteria, parasites). In rats pregnant by syngeneic and
      allogeneic males, the ratio asymmetric/symmetric IgG molecules increases, and the
      anti-ovalbumin antibodies are mainly of the asymmetrical IgG type, which aid
      antigen-blocking. Similar results are found in virgin rats, immunized with
      ovalbumin and intraperitoneally transferred simultaneously with supernatants of
      placental cultures. These results suggest that, during pregnancy, there is an
      increase of the IgG asymmetric/symmetric molecule ratio, produced by placental
      factors, whatever the immunogen specificity may be. Speculations about this fact
      are presented.

PMID- 7738913
TI  - In vivo inhibition of cell-mediated and humoral immune responses to cellular
      antigens by SV-IV, a major protein secreted from the rat seminal vesicle
      epithelium.
AB  - Microgram amounts of protein SV-IV, a major secretory protein produced by adult
      rat seminal vesicle epithelium, markedly decrease the mouse humoral immune
      response to cellular xenogeneic or allogeneic antigens (sheep red blood cells
      (SRBC) or mouse epididymal spermatozoa). The significant reduction in the total
      number of splenocytes and their main cell subsets in SRBC-immunized mice, the
      dramatic decrease in the number of Ia+ splenic T cells and the marked inhibition
      of splenocyte ability to respond in vitro to polyclonal mitogen stimuli suggest
      that the macrophage accessory cells are the primary target of the SV-IV
      immunosuppressive activity in vivo. Moreover, the infection of SV-IV-treated mice
      with Salmonella typhimurium produced an increased mortality of the experimental
      animals associated with a marked decrease of the phagocytic and intracellular
      killing activities of their peritoneal macrophages.

PMID- 7738914
TI  - Synthesis and granular localization of tumor necrosis factor-alpha in activated
      NK cells in the pregnant mouse uterus.
AB  - The synthesis and cellular localization of tumor necrosis factor-alpha (TNF
      alpha) were studied in mouse GMG cells, which are activated NK cells in uterine
      decidual tissue during pregnancy. Synthesis of the protein was demonstrated in
      GMG cells on days 10 and 14 of pregnancy by in situ hybridization of TNF-alpha
      message. Immunostaining demonstrated that TNF-alpha protein was localized in the
      cytoplasmic granules of GMG cells at these times. The results suggest that the
      cytolytic activity of uterine NK cells may be due in part to TNF-alpha, and that
      this cytokine may be delivered to target cells intracellularly via transmembrane
      pores formed by perforin, which is also localized in uterine NK cell granules.

PMID- 7738915
TI  - Autoantibodies to phospholipids and nuclear antigens in non-pregnant and pregnant
      Colombian women with recurrent spontaneous abortions.
AB  - Autoantibodies to negatively charged phospholipids have been reported to be
      associated with thrombotic events, thrombocytopenia and adverse pregnancy
      outcome, such as intrauterine growth retardation and recurrent spontaneous
      abortions (RSAs). In this study, autoantibodies to 6 phospholipid antigens and
      antinuclear antibody (ANA) were tested in Colombian women with a history of RSAs.
      Sixty-eight non-pregnant and 25 pregnant women with a history of RSAs comprised
      the study group. Twenty-five non-pregnant normal healthy women and thirty-one
      normal pregnant women served as controls. The non-pregnant women with RSAs showed
      a higher incidence of autoantibodies to cardiolipin (23% positive) as compared
      with non-pregnant normal controls (0% positive; P < 0.005). The incidence of
      autoantibodies to cardiolipin (28%; P < 0.005), phosphatidylethanolamine (16%; P
      < 0.005), phosphatidylserine (16%; P < 0.05), phosphatidylglycerol (16%; P <
      0.05), phosphatidic acid (16%; P < 0.01) and phosphatidylinositol (20%; P <
      0.01), in the pregnant women with RSAs was significantly higher than that of
      normal pregnant controls. There was no difference in the incidence of ANA in
      either group. In conclusion, women with a history of RSAs have a higher incidence
      of autoantibodies to phospholipids when compared to pregnant and non-pregnant
      normal controls. Autoimmune serological work-up is indicated during pregnancy in
      women with a history of RSAs.

PMID- 7738916
TI  - Characterization of human sperm antigens reacting with antisperm antibodies from
      autologous sera and seminal plasma in a fertile population.
AB  - Immunoblotting techniques were used to characterize the reactivity of human sperm
      antigens with antisperm antibodies from a population of fertile individuals. In
      particular, sperm antigens of each subject were tested with the same subject's
      antisperm antibodies present in blood serum and seminal plasma in an attempt to
      construct a preliminary map of the antigen domains of the normal spermatozoon.
      Fifty-five fertile males, comprising 22 subjects with a pregnant partner and 33
      subjects attending assisted reproductive technology sessions for proven partner's
      infertility and with normal semen quality entered the study. A high proportion of
      sera (82%) and seminal plasma (62%) showed antisperm antibodies reacting with one
      or more sperm antigens. Specific immunoreactivity was often demonstrated to 45
      kDa, 50-kDa, 55-kDa, 69-kDa, 72-kDa and 85-kDa proteins in serum and to 59-kDa
      and 72-kDa proteins in seminal plasma. These proteins are the most frequently
      involved sperm antigens in the immune responses in fertile subjects. Further
      studies in an infertile population are necessary to distinguish between these
      antigens of minor relevance in sperm function from others significantly involved
      in immunological infertility.

PMID- 7738917
TI  - Failure of thyroid allografts to function in the testes of cynomolgous monkeys.
AB  - Allografts of thyroid were placed into one testis of 8 cynomolgous monkeys. None
      of these had accumulated significant amounts of radioactive iodide 28 days later,
      whereas autografts of thyroid placed in the other testis of 6 of these monkeys
      did so in 5 cases out of the 6. Autografts of thyroid placed subcutaneously in
      these 6 monkeys also accumulated iodide in the same 5 animals, but subcutaneous
      allografts failed in all 6 monkeys in which these were done. These results
      suggest that there is no immune privilege for grafts in the primate testis, which
      in this regard resembles more the testis of the ram, rather than that of rodents.

PMID- 7738918
TI  - Compliance with the 24-hour, in-house attending coverage requirement. A survey.
AB  - Fifty-six residency training programs in Region I Council on Resident Education
      in Obstetrics and Gynecology/Association of Professors in Gynecology and
      Obstetrics were surveyed for compliance with the 24-hour, in-house attending
      coverage requirement, which took effect July 1991. Forty-six program directors
      responded to a questionnaire, for a response rate of 82.1%. Each had plans to
      implement this coverage in the 1991-1992 academic year. Two programs were unable
      to implement coverage because of inadequate financing or insufficient staffing.
      There were no differences in the types of programs (community, university, public
      or private university, or New York State program) in respondents as compared to
      non respondents. All the programs had overnight staff coverage for an average of
      13 hours (range, 12-15) and had 24-hour, continuous coverage on the weekend.
      There was a wide variation in the attending/resident ratio. Twenty-eight programs
      (60.8%) reported that they compensated their attendings. Revenue for this
      compensation came from the hospitals (14), direct billing (8), faculty practice
      plans (6) or New York State (3). Of the 28 programs that offered compensation, 20
      were private community hospitals, 6 were private university programs, 1 was a
      public university program and 1 was a public community hospital. Of the 28
      programs compensating faculty, 17 were able to cite figures that had been
      approved by their respective institutions or practice plans. The annual cost
      ranged from $130,300 to $901,887 per program for institutions that compensated
      their attendings (mean, $340,402).

PMID- 7738920
TI  - Dissecting the pelvic retroperitoneum and identifying the ureters. A laparoscopic
      technique.
AB  - A technique for dissecting the pelvic retroperitoneum and identifying the ureters
      and uterine arteries is described that makes use of the obliterated hypogastric
      arteries. The obliterated arteries are readily identified laparoscopically and,
      as relatively fixed structures, are easily dissected free of the bladder and
      surrounding areolar tissues. Once freed by blunt dissection, they are traced
      proximally to where they are joined by the uterine arteries to form the internal
      iliac arteries. Blunt dissection just proximal and medial to the uterine artery
      will open the pararectal space, the medial border of which is bounded by the
      ureter. The uterine arteries are then traced to where they cross the ureters and
      are freed from them by blunt dissection. The site at which the uterine arteries
      are divided and the extent to which the extraperitoneal spaces are developed and
      ureters mobilized off the medial leaf of the broad ligament are tailored to the
      operation performed.

PMID- 7738919
TI  - Amnioinfusion.
AB  - Amnioinfusion is a relatively new technique with a variety of uses. Its most
      common application is the treatment of variable decelerations in the fetal heart
      rate during labor. By artificially increasing the amniotic fluid volume, the
      umbilical cord is better protected from compression. Amnioinfusion can represent
      the difference between operative intervention and spontaneous vaginal delivery.
      This simple, inexpensive technique appears to pose little risk and warrants
      consideration for the properly selected patient.

PMID- 7738921
TI  - Warming fluid for amnioinfusion during labor.
AB  - While it has never been shown that warming fluid to body temperature prior to
      using it for amnioinfusion in labor is necessary, the practice is generally
      accepted. Ideally it is done with a blood warmer. Since blood warmers are
      expensive and not always available, fluid bags are often warmed in "constant
      temperature" devices used to heat blankets and fluid used in surgery. These units
      are ubiquitous, create no extra expense with their use and are a reasonable
      alternative to blood warmers. A study was designed to determine whether warming
      ovens actually did heat the fluids used for amnioinfusion to around 37 degrees C.
      Fluid bags were placed in the warming oven for 48 hours or more, and opening
      temperatures of the contained fluids were recorded. The temperatures were
      extremely variable, ranging from 21 degrees C to > 50 degrees C. The variability
      in opening temperatures was a result of wide temperature fluctuations in the
      warming oven itself and the condition of the fluid bags on removal. Blanket and
      surgical fluid warming ovens are not appropriate for heating fluids used in
      amnioinfusion during labor.

PMID- 7738922
TI  - Vacuum extraction of preterm infants with birth weights of 1,500-2,499 grams.
AB  - This study evaluated neonatal morbidity in preterm infants with birth weights of
      1,500-2,499 who were delivered by vacuum extraction. The retrospective,
      observational study covered 61 infants delivered vaginally with vacuum extraction
      versus 122 matched controls delivered spontaneously. All infants were at < 37
      weeks of gestation, with birth weights ranging from 1,500 to 2,499 g. Main
      neonatal outcomes studied were Apgar scores, umbilical artery blood pH and base
      excess, intraventricular hemorrhage, admission to the neonatal intensive care
      unit and length of hospital stay. The study population did not differ in any
      maternal or neonatal demographic parameter. There was a decreased need for
      episiotomies in the vacuum-assisted deliveries versus the controls (41% versus
      57%, P = .01, odds ratio = .51, confidence interval = .27, .96). Neonatal
      morbidity was not significantly different in infants with vacuum-assisted
      deliveries. Vacuum extraction does not seem to increase neonatal morbidity in
      preterm infants with birth weights of 1,500-2,499 g.

PMID- 7738923
TI  - Combined vaginal-abdominal delivery of twins.
AB  - All cases of combined vaginal-abdominal deliveries at the Department of
      Obstetrics and Gynecology, Chaim Sheba Medical Center, over an eight-year period
      (1984-1991) were reviewed. During this period a total of 38,821 deliveries took
      place. Of 722 (1.9%) twin deliveries, 354 (48.8%) were by cesarean section; 19
      were combined deliveries, including 5% of all twins delivered by cesarean section
      and 2.6% of all twins delivered. High transverse lie and prolapse of the
      umbilical cord were the main indications for delivery by cesarean section of the
      second twin. In order to diminish the number of combined deliveries and to
      increase obstetric skills and experience, a program or protocol for vaginal twin
      deliveries is indicated.

PMID- 7738924
TI  - Fetal surveillance. Should it begin at 40 weeks' gestation in a low-risk
      population?
AB  - We evaluated the possible benefits of antepartum surveillance during the 41st
      week of pregnancy in a low-risk population. Three hundred low-risk patients
      (study group) underwent a nonstress test (NST) at the beginning of the 41st week
      of pregnancy. Outcomes in study group patients who delivered during the 41st week
      were compared to those in 100 similar control patients who were not tested. One
      antepartum fetal demise occurred in each group: study group rate, 1/300 (0.3%);
      control group rate, 1/100 (1%), P > .05. During the 41st week, 158 of 300 (53%)
      study patients and 59 (59%) control patients delivered. Four of 158 (2.5%) study
      patients had labor induced for the indication of an abnormal antepartum test
      during the 41st week. Cesarean delivery for distress during the 41st week was
      performed on 1/157 (0.6%) study and 1/58 (1.7%) control patients (P > .05). No
      statistically significant improvement in outcome occurred in the study group even
      though 4 of 300 study group patients required induction of labor for abnormal
      antepartum testing during the 41st week of gestation. The current practice of not
      evaluating low-risk pregnancy with an NST until after the completion of 41 weeks
      is supported by the results of this study.

PMID- 7738925
TI  - Laparoscopic removal of pelvic splenosis. A case report.
AB  - Splenosis is the autotransposition of splenic tissue and is rarely encountered by
      the gynecologist. Most patients with splenosis are asymptomatic but may present
      with gynecologic symptoms. There are few reports in the gynecologic literature
      describing the management of pelvic splenosis. This paper reports the first case
      of laparoscopic management of pelvic splenosis.

PMID- 7738927
TI  - Vulvar leiomyoma associated with estrogen/progestin therapy. A case report.
AB  - Leiomyomata of the vulva are reported rarely. A previously unrecognized leiomyoma
      in the area of Bartholin's gland grew rapidly during estrogen/progestin
      replacement therapy. Hormone receptors for both estrogen and progesterone were
      positive.

PMID- 7738928
TI  - Bladder pheochromocytoma in pregnancy without hypertension. A case report.
AB  - A 33-year-old nullipara presented at 20 weeks' gestation with episodes of
      nonsustained ventricular tachycardia, which were controlled with amiodarone. No
      hypertension was recorded except once after an attack of ventricular tachycardia.
      Pheochromocytoma was suspected when repeat 24-hour urine catecholamine levels
      were markedly elevated. Neither computed tomography nor postpartum
      metaiodobenzylguanidine scan could locate the tumor. Finally it was identified in
      the bladder by ultrasound after selective venous sampling localized it to the
      pelvis. It was excised four months postpartum.

PMID- 7738929
TI  - Spontaneous pneumothorax during operative laparoscopy secondary to congenital
      diaphragmatic defects. A case report.
AB  - As operative laparoscopy increases in popularity and use, so will the number and
      variety of complications associated with it. Laparoscopists should be cognizant
      of techniques for avoiding complications as well as alert to conditions that
      result in complications. We report an operative laparoscopic procedure that
      resulted in a complete right pneumothorax. This complication developed because of
      congenital diaphragmatic defects and was recognized and appropriately treated
      intraoperatively. The combination of the defects with the increased
      intraperitoneal pressure from laparoscopy resulted in the pneumothorax. The
      incidental diagnosis of diaphragmatic defects during laparoscopic surgery has not
      been reported before.

PMID- 7738926
TI  - Use of the GnRH agonist stimulation test in the diagnosis of ovarian remnant
      syndrome. A report of three cases.
AB  - Ovarian remnant syndrome is an uncommon problem that may follow bilateral
      oophorectomy. These patients may present with chronic pelvic pain or pelvic
      masses and may require surgery to confirm or exclude the diagnosis. In this
      report we describe the successful use of the gonadotropin releasing hormone
      agonist (GnRH-a) stimulation test to identify the presence of functioning ovarian
      tissue in three women with ovarian remnant syndrome who presented for evaluation
      of persistent chronic pelvic pain. In these cases the endogenous gonadotropin
      flare was able to stimulate the production of significant quantities of estradiol
      to confirm the diagnosis. The GnRH-a stimulation test may be a useful adjunct in
      the evaluation of women at risk for ovarian remnant syndrome prior to proceeding
      with surgery.

PMID- 7738931
TI  - Salmonella typhi chorioamnionitis in a human immunodeficiency virus-infected
      pregnant woman. A case report.
AB  - Opportunistic prenatal infection is a recognized problem in human
      immunodeficiency virus (HIV)-infected women from inner city communities. We
      report a case of intrapartum Salmonella typhi infection and discuss the possible
      route of infection. An HIV-infected pregnant woman was admitted for fever and
      ruptured membranes. Maternal blood, cervical and uterine cultures, and placental
      surface and intramembranous space cultures grew S typhi. The patient responded to
      antibiotic therapy, with no relapse. The infant did not show signs or symptoms of
      Salmonella sepsis. Salmonella infection should be treated aggressively in HIV
      infected pregnancies with chorioamnionitis and postpartum endometritis.

PMID- 7738930
TI  - Intracranial meningioma with positive progesterone receptors. A case report.
AB  - A patient with a headache and seizures in the second trimester of her fifth
      pregnancy was diagnosed as having an intracranial meningioma. She underwent
      pregnancy termination followed by craniotomy and removal of the tumor one week
      later. She recovered fully. The final pathology report confirmed the diagnosis of
      meningioma, progesterone receptor positive.

PMID- 7738932
TI  - Transverse vaginal septum. A case report.
AB  - A case occurred of imperforate, complete transverse vaginal septum in the lower
      third of the vagina. The patient presented at 16 years of age with primary
      amenorrhea and was found to have hematocolpos. The clinical impression was an
      imperforate hymen because of the very low position of the septum in the vagina.
      After excision the diagnosis of transverse vaginal septum was made histologically
      because of the presence of mullerian duct (mesodermal origin) tissue in the
      septum. The patient also had syndactyly of the second and third toes on her right
      foot. The association of these two congenital abnormalities has not been reported
      previously.

PMID- 7738933
TI  - Nafarelin acetate for pituitary down-regulation in in vitro fertilization.
      Comparison of two dosages.
AB  - The objective of this study was to evaluate the efficacy of intranasal (IN)
      nafarelin acetate (NA), 400 micrograms/d and 600 micrograms/d, in a luteal-phase
      start, long protocol in women undergoing their first in vitro fertilization (IVF)
      cycle. A sequential comparison of 200 consecutive first IVF cycles, the study was
      performed in the Department of Gynaecology and Reproductive Medicine, University
      Hospital, London, Ontario, Canada. The participants were 200 first-cycle IVF
      patients who were regularly cycling--100 NA 400 micrograms IN followed by 100 NA
      600 micrograms IN. Eighty-two percent of the NA 400 micrograms group were
      adequately suppressed after 11 days of treatment (serum estradiol < or = 150
      pmol/L) as compared to 87% with NA 600 micrograms/d. These results compare
      favorably with those in a historical control group of 179 subjects receiving
      daily leuprolide acetate (LA), 0.5 mg subcutaneously, in their first cycle of
      IVF. The amount of human menopausal gonadotropin required for optimal follicular
      development was similar for the two NA groups. Clinical pregnancy rates were 13%
      per cycle and 21.7% per embryo transfer (ET) for NA 400 micrograms od and 19% per
      cycle and 30.1%/ET for NA 600 micrograms od (normal standard dose). No
      spontaneous luteinizing hormone (LH) surges occurred in any subject. Patient
      counseling and instruction time for NA use, which required nursing time, averaged
      five minutes per patient and an additional five minutes of video-viewing time.
      NA, 400 micrograms and 600 micrograms per day, appear to be acceptable alternate
      choices for pituitary down-regulation in a luteal-phase-start, long down
      regulation protocol for IVF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7738934
TI  - Prevention of exercise incontinence with mechanical devices.
AB  - A prospective, randomized, single-blind study addressed the hypothesis that
      simple mechanical barriers are helpful in controlling urinary incontinence during
      exercise. Eighteen incontinent exercisers aged 33-73 participated in three 40
      minute standardized aerobics sessions wearing either a Hodge pessary with
      support, a super tampon or no mechanical device. Urine loss was determined by a
      change in the weight of the pad worn while exercising. Statistical analysis of
      the log of urine loss revealed that women lost significantly less urine when
      exercising with either the pessary or the tampon than when exercising with no
      device. Thus, both devices studied are useful, nonsurgical alternatives for some
      women for the treatment of exercise incontinence.

PMID- 7738936
TI  - Imperfect indications of disease activity in juvenile dermatomyositis.

PMID- 7738935
TI  - Risk of preterm delivery from preterm labor in high-risk patients.
AB  - This study aimed to determine the incidence of preterm labor and birth (< 37
      weeks' gestation) in patients at high risk for early delivery. In this
      retrospective, descriptive study, 17,186 women with high-risk factors for early
      delivery were studied over a five-year period (1986-1990). Study groups included
      women with prior preterm delivery, multifetal gestations, uterine abnormalities
      and cervical factors. The rate of preterm labor for all patients averaged 40%
      (range, 30-46%). The rate of preterm delivery in the four groups ranged from 14%
      to 30% and averaged 19.7%. In those who experienced preterm delivery, only 32% of
      cases were due to preterm labor with advanced cervical dilatation, failed
      tocolysis or preterm premature rupture of membranes. The majority of early
      deliveries were due to medical or obstetric disorders as well as to
      patient/physician factors. The incidence of preterm labor remains significant
      when women have high-risk factors for preterm delivery. However, the incidence of
      preterm delivery, particularly that due to avoidable factors, such as failed
      tocolysis and preterm rupture of the membranes, is considerably lower than that
      quoted in the literature.

PMID- 7738937
TI  - Silicone breast implants and connective tissue diseases: an ongoing controversy.

PMID- 7738938
TI  - Detecting and measuring disease modification in osteoarthritis. The need for
      standardized methodology.

PMID- 7738939
TI  - The economic burden of musculoskeletal disorders in Canada is similar to that for
      cancer, and may be higher.

PMID- 7738940
TI  - Upper limb lymphatic function in inflammatory arthritis.
AB  - OBJECTIVE: To determine the effect of inflammatory arthritis on lymphatic
      function in the upper limb. METHODS: Lymphoscintigraphy was used to measure
      lymphatic drainage in the upper limbs of 3 groups of patients: Group 1,
      inflammatory arthritis and edema (N = 10); Group 2, inflammatory arthritis and no
      edema (N = 18); and Group 3, healthy controls (N = 11). RESULTS: Lymphatic
      drainage was reduced significantly in Group 1 but was the same in Groups 2 and 3.
      Multiple regression analysis failed to show any effect of arthritis on lymphatic
      drainage. CONCLUSION: Inflammatory arthritis alone does not impair lymphatic
      drainage in the upper limbs. The results suggest that the presence of edema is
      primarily attributable to an unrelated abnormality influencing lymphatic
      function.

PMID- 7738941
TI  - The effect of age and renal function on the efficacy and toxicity of methotrexate
      in rheumatoid arthritis. Rheumatoid Arthritis Clinical Trial Archive Group.
AB  - OBJECTIVE: To evaluate whether age and renal impairment affect the rate of side
      effects or expected efficacy of methotrexate (MTX) in rheumatoid arthritis (RA).
      METHODS: Data was pooled from 11 MTX clinical trials containing 496 patients
      treated with MTX. We evaluated those patients less than 60 years old and those in
      5-year groupings of age over age 60. Using serum creatinine, weight, and age, we
      calculated creatinine clearance and placed patients into quartiles based on their
      baseline creatinine clearance. To evaluate efficacy, we used changes in American
      College of Rheumatology core set efficacy measures available in these trials. To
      quantify side effects, we scored each side effect based on a modified Fries
      toxicity score and assigned each patient a score based on the worst side effect
      experienced during the trial. We also separately evaluated liver toxicities
      (twice normal elevation of AST or ALT), respiratory toxicity and severe
      toxicities. Intent-to-treat analyses were performed, adjusting for study of
      origin. Results were confirmed by placebo controlled trials, comparing MTX and
      placebo treated patients. RESULTS: Neither age nor renal impairment had any
      effect on the efficacy of MTX. Those in the oldest age groups (65-69 years, > or
      = 70 years) were not at higher risk of side effects from MTX. However, patients
      with renal impairment had a higher overall rate of toxicity and were at higher
      risk of severe and respiratory toxicities than those whose creatinine clearances
      were at least 99.8 ml/min (reference group). The odds of severe toxicity were
      increased roughly 4-fold in those with renal impairment. CONCLUSION: Among
      clinical trial patients, age does not affect MTX efficacy or the rate of side
      effects. Renal impairment, however, increases the risk of side effects.

PMID- 7738942
TI  - Interleukin 6 (IL-6) and soluble IL-2 receptor levels in patients with rheumatoid
      arthritis treated with low dose oral methotrexate.
AB  - OBJECTIVE: To investigate the effect of oral methotrexate (MTX) on circulating
      levels of interleukin 6 (IL-6) and soluble IL-2 receptor (sIL-2R) in patients
      with rheumatoid arthritis (RA). METHODS: We measured serum concentrations of IL-6
      (n = 20) and sIL-2R (n = 16) before MTX therapy and again after 12 weeks.
      RESULTS: MTX significantly reduced IL-6 and sIL-2R after 12 weeks of therapy, and
      although the levels remained low at 24 weeks of therapy, the reduction was not
      significant. Reduction in cytokine levels was paralleled by an improvement in
      clinical indices. Placebo treatment did not significantly alter IL-6 or sIL-2R.
      CONCLUSION: MTX appears capable of cytokine modulation, although the mechanism is
      not clear.

PMID- 7738943
TI  - Familial anticardiolipin antibodies and C4 deficiency genotypes that coexist with
      MHC DQB1 risk factors.
AB  - OBJECTIVE: To investigate the familial basis of antiphospholipid antibodies by
      studying putative risk factors at the C4 and MHC class II loci. METHODS:
      Autoimmune diseases, anticardiolipin (aCL) and other autoantibodies were studied
      in 38 first and 2nd degree family members of 3 index cases selected for primary
      antiphospholipid syndrome (APS) and 33 controls. C4 protein phenotyping and
      restriction fragment length polymorphism analysis of C4 and MHC class II loci
      were performed. RESULTS: Nineteen family members (46%) had autoimmune diseases or
      autoantibodies; aCL were present in 10 family members, 4 of whom had primary APS.
      Each family had 2 or more subjects with aCL. Among 22 independent haplotypes in
      family members, there was a high frequency of C4A and C4B deficiency alleles
      (0.41 vs 0.18 in 66 controls, p = 0.03) and a strong trend toward an increase in
      MHC DQB1 putative risk factors that share the TRAELDT structural domain. This
      DQB1 structural domain was present in 4/5 different haplotypes that contained a
      C4B deficiency genotype; however, neither of 2 different haplotypes with a C4A
      deletion (one being a common ancestral haplotype) contained this DQB1 putative
      risk factor. Among the 10 family members who had aCL, 10/20 haplotypes contained
      a C4 deficiency genotype; moreover, the DQB1 putative risk factor was present in
      all 16 MHC haplotypes that did not contain a C4A deletion. CONCLUSION: In these
      families, expression of an autoimmunity trait as aCL antibody appears to be
      associated with the coexistence of C4 deficiency alleles with DQB1 alleles that
      contain the TRAELDT structural domain.

PMID- 7738945
TI  - Longterm methotrexate therapy in psoriatic arthritis: clinical and radiological
      outcome.
AB  - OBJECTIVE: To determine whether methotrexate (MTX) therapy for 24 months prevents
      progression of radiographic damage in psoriatic arthritis (PsA). METHODS:
      Patients who were given MTX during their attendance at the psoriatic arthritis
      clinic were enrolled in the study. Patients who had never had MTX and who were
      matched by damage, actively inflamed joints, sex, and disease duration were
      identified from the PsA database as controls. The outcome measure was increase in
      the number of damaged joints. RESULTS: The study population comprised 38 patients
      (16 F, 22 M) with a mean age of 44.6 years and disease duration of 11.4 years.
      Twenty-three patients continued therapy for 24 months. Clinical evaluation
      revealed that 45% of the patients had > or = 40% improvement in actively inflamed
      joint count at 6 and 24 months. Radiographs were available for 19 of the 23
      patients who took MTX for 24 months, and they were compared to their respective
      controls. Radiographic damage scores at 24 months showed an increase in the
      damage score in 63% of the patients. Compared to the matched controls, there was
      no statistically significant difference in the progression in damage. CONCLUSION:
      Our results suggest that compared to other regimens, MTX conferred no advantage
      with respect to clinical response or longterm damage even after 24 months of
      therapy.

PMID- 7738944
TI  - Serum antinuclear antibodies in women with silicone breast implants.
AB  - OBJECTIVE: Recent evidence suggests that immunologic abnormalities are not
      uncommon in individuals with silicone breast implants. The purpose of our study
      was to evaluate in a consecutive manner, the prevalence of autoimmunity as
      assessed by the presence of antinuclear antibodies in a larger number of patients
      with silicone breast implants. METHODS: Antinuclear antibody (ANA) testing using
      an indirect immunofluorescence technique was performed on 813 individuals with
      silicone breast implants. All subjects except for 3 transsexual males, were
      female. The overwhelming majority, over 99%, were white. The average age of the
      subjects was 46.2, with a range of 17 to 72 years. RESULTS: ANA positivity was
      found in 244 of 813 individuals (30%) using a mouse kidney substrate; and in 470
      of 813 (57.8%) using a HEp-2 cell line. The most common immunofluorescent pattern
      found using HEp-2 was speckled, present in 341 (72.5%) individuals, followed by
      homogeneous pattern in 113 (24%), nucleolar in 63 (13.4%), and 5 (1.06%) were
      anticentromere. Anti-dsDNA antibodies measured by an ELISA assay were found in 6
      of 71 patients (8%). Rheumatoid factor and C-reactive protein were found above
      healthy controls in less than 10% of cases studied. The high prevalence of ANA
      found in patients with silicone breast implants agrees with similar observations
      by others. The finding of anticentromere and nucleolar patterns has great
      interest and relevance. These fairly distinct ANA patterns are most commonly seen
      in the idiopathic form of scleroderma and related conditions. CONCLUSION: These
      findings suggest that ANA positivity is relatively common in individuals with
      silicone breast implants, and may support the existence of autoimmune mechanisms
      in the pathogenesis of the clinical manifestations seen in this population.

PMID- 7738946
TI  - Assessment of 2 systems of spondyloarthropathy diagnostic and classification
      criteria (Amor and ESSG) by a Spanish multicenter study. European
      Spondyloarthropathy Study Group.
AB  - OBJECTIVE: To assess the 2 most recently developed sets of spondylarthropathy
      (SpA) diagnostic and classification criteria [Amor and the European
      Spondyloarthropathy Study Group (ESSG)] in a survey involving a Spanish
      population with rheumatic disease. METHODS: The survey involved a cross sectional
      study of 1549 patients with rheumatic disease, who were examined over a week by
      36 expert rheumatologists at 28 Spanish rheumatological centers. The head
      researcher at each participating center was to diagnose patients as having
      definite SpA, possible SpA, or as having other rheumatic diseases (definite
      controls) based on the physician's experience and assessment with no reference to
      the criteria under study. RESULTS: Overall a total of 218 patients were
      classified as having definite SpA, 1242 as definite controls and 89 as having
      possible SpA. An analysis of the patients diagnosed as definite showed 90.8 and
      83.5% sensitivity, 96.2 and 95.2% specificity, 80.8 and 75.5% positive predictive
      value, and 98.4 and 97.0% negative predictive value for the Amor and ESSG
      criteria sets, respectively. CONCLUSIONS: Both the Amor and ESSG criteria had
      excellent intrinsic (sensitivity and specificity) and extrinsic (positive and
      negative predictive value) performance, with no substantial differences between
      the 2. The results support use of the criteria for classifying SpA in daily
      rheumatological practice. Although not intended as diagnostic criteria, they make
      useful tools for the early identification of initial, atypical, or
      undifferentiated forms, which fail to strictly meet the diagnostic criteria of
      the entities that make up the SpA group.

PMID- 7738947
TI  - Change in the epidemiology of Reiter's syndrome (reactive arthritis) in the post
      AIDS era? An analysis of cases appearing in the Greek Army.
AB  - OBJECTIVE: During the last 5 years we observed a significant decrease in the
      incidence of newly established cases of Reiter's syndrome (reactive arthritis) in
      Greek Army personnel. Our study was initiated to validate this observation and to
      evaluate a possible change in the prevalence of Reiter's syndrome (RS) associated
      infections. METHODS: The case records of patients with reactive arthritis (ReA)
      admitted during the periods 1980-83 and 1989-92 at a large Army Hospital were
      studied retrospectively and the cases of RS were reviewed. In addition, the
      prevalence of cases with urethritis and dysentery that presented to the hospital
      in the same periods was studied in retrospect, as these infections are known to
      participate in the etiopathogenesis of RS. RESULTS: A significant decrease in the
      overall incidence of the randomly presented RS cases during the second 4 year
      period was detected (27 versus 4 cases, p < 0.0001, chi 2 test). A similar
      significant decrease in the number of cases with gonococcal and nongonococcal
      urethritis was observed while the prevalence of dysentery was not significantly
      altered during the defined intervals. CONCLUSION: We suggest that the anti-AIDS
      campaign which began after the years 1984-85 is the principal cause of the
      observed change of epidemiology of RS cases appearing in the Greek Army.

PMID- 7738948
TI  - Type II procollagen gene (COL2A1) mutation in exon 11 associated with
      spondyloepiphyseal dysplasia, tall stature and precocious osteoarthritis.
AB  - OBJECTIVE: To define the clinical, pathological and molecular genetic
      characteristics of a family with mild spondyloepiphyseal dysplasia (SED) and
      precocious osteoarthritis. METHODS: The proband was a 46-year-old man with
      precocious generalized OA, tall stature, mild chondrodysplasia and moderate
      deafness. His daughter, aged 21, showed similar clinical features. Electron
      microscopic (EM) analysis of collagen from an affected joint of the proband was
      performed. DNA was extracted from whole blood on the proband, his affected
      daughter, unaffected wife and second daughter, to look for a mutation in exons 31
      or 11, sites where point mutations have been previously described in mild forms
      of SED. After finding no mutation in exon 31, exon 11 of COL2A1 was further
      analyzed. Exon 11 was amplified using polymerase chain reaction (PCR), and
      screening for the mutation was undertaken using a restriction enzyme digestion,
      the recognition sequence of which is altered by this point mutation. Sequence
      analysis was then performed. RESULTS: Electron microscopic (EM) analysis of
      cartilage from the proband showed thin appearing collagen fibrils organized into
      parallel lamellar structures. DNA studies revealed a single base change in one
      allele of exon 11 which produced an arginine to cysteine mutation at position 75
      of the triple helix of type II collagen in the proband and his affected daughter.
      CONCLUSION: This is the 2nd example of an Arginine75-Cysteine mutation associated
      with SED; in our case, however, contrasting clinical features were present.
      Recurrent mutations at a few specific sites of COL2A1 suggest the possibility of
      susceptibility "hot spots" for mutational events.

PMID- 7738950
TI  - Fibromyalgia versus rheumatoid arthritis: a longitudinal comparison of the
      quality of life.
AB  - OBJECTIVE: To evaluate and compare the quality of life of patients with
      fibromyalgia (FM) and rheumatoid arthritis (RA). METHODS: Forty-four women with
      FM and 41 with RA were studied. There were 3 evaluations, with a 3-month
      interval. Besides special and general clinical examinations, the following tests
      were applied: pain numerical scale (PNS), Health Assessment Questionnaire (HAQ),
      Fibromyalgia Impact Questionnaire (FIQ), Arthritis Helplessness Index (AHI),
      Modified Post-Sleep Inventory (PSI), and questions about sleep disorders and
      socioeconomic impact. RESULTS: Results include the following: tender points (TP):
      FM = 13.9, RA = 2.9; PNS: FM = 7.2, RA = 6.8; HAQ: FM = 0.90, RA = 1.22; FIQ: FM
      = 47.2, RA = 42.5; AHI: FM = 32.7, RA = 31.8; sleep quality--mean duration of
      daily sleep: FM = 6.7 h, RA = 6.1; PSI scores: FM = 64.6, RA = 57.2. On
      questioning regarding economic impact, there was a decrease in family income for
      65% of patients with FM and 75.1% for those with RA. Fifty-five percent of
      patients with FM and 66.6% of those with RA received social security aid. At
      followup evaluation, there was a statistically significant improvement in the
      following items for the patients with FM: TP count, HAQ, and AHI. The patients
      with RA improved in number of TP and AHI. CONCLUSION: FM has a negative impact on
      quality of life, similar to RA. Clinical, functional, and economic problems
      related to the disease were observed. The alteration observed remained relatively
      stable during the study period, except for physical disability.

PMID- 7738949
TI  - Rapid and sustained rise in the serum level of hyaluronan after anterior cruciate
      ligament transection in the dog knee joint.
AB  - OBJECTIVE: To monitor changes in serum levels of hyaluronan (HA) in experimental
      canine osteoarthritis (OA), and to relate these changes to the level of HA in
      synovial fluid (SF) and/or to the rate of HA synthesis by synovium. METHODS: OA
      was induced in 16 dogs by anterior cruciate ligament transection; 7 dogs were
      sham operated. An immunoassay was used to measure HA levels in serum at various
      times postsurgery and in SF from OA knees at sacrifice (Week 13 postsurgery). The
      rate of HA synthesis by synovium from both knees of 9 OA dogs and 5 sham operated
      dogs was measured at 13 weeks. RESULTS: The serum level of HA showed a minor
      transient rise postsurgery in sham operated dogs. In all OA dogs, this rise was
      marked and sustained and correlated with the SF level of HA. Further, in OA dogs,
      the rate of HA synthesis by synovium was elevated in both the operated OA knee
      and the nonoperated knee. CONCLUSION: The sustained rise in the serum level of HA
      in OA dogs appears to be the result of increases in the rate of HA synthesis by
      synovium in both the operated and nonoperated knees, and possibly in other
      synovial joints.

PMID- 7738951
TI  - Detection of insulin-like growth factor I and II in synovial tissue specimens of
      patients with rheumatoid arthritis and osteoarthritis by in situ hybridization.
AB  - OBJECTIVE: To study the expression of insulin-like growth factor I and II (IGF I
      and II) in synovial tissue specimen of patients with rheumatoid arthritis (RA)
      and osteoarthritis (OA). METHODS: Synovial tissue sections were examined for the
      expression of IGF I and II by in situ hybridization using digoxigenin labeled
      antisense and sense RNA probes. RESULTS: The antisense probe of IGF I reacted
      with all specimens. IGF II mRNA was expressed in 7/7 RA and 4/5 OA tissues. Cells
      of the synovial lining and subsynovial layer bound both antisense probes, whereas
      inflammatory infiltrates of RA tissues were labeled rarely. CONCLUSION: The
      significant number of cells in the synovium that express IGF I and II mRNA
      suggests a role of IGF in repair mechanisms of articular cartilage in response to
      injury and effects on fibroblast growth within the synovium.

PMID- 7738953
TI  - 1994 Abe Shore Memorial Lecture. Impending discoveries in pediatric rheumatology.

PMID- 7738954
TI  - The natural history of juvenile chronic arthritis: a population based cohort
      study. I. Onset and disease process.
AB  - OBJECTIVE: To study the natural history and the disease process in a population
      based cohort of patients with juvenile chronic arthritis (JCA) who were in the
      process of being transferred from pediatric to adult rheumatology care. METHODS:
      From a prospective population based epidemiological study in southwestern Sweden
      the cohort of patients with JCA born from 1968 through 1972 were investigated
      after a median disease duration of 7.1 years. The study cohort constituted of 124
      patients with median age 17.7 years. RESULTS: At followup 49.2% patients still
      required medication, 20.2% had inactive disease and 30.6% were in remission. The
      highest risk of continuing disease activity was observed in patients with short
      disease duration (RR = 9.0) or very long duration (RR = 2.5) compared with those
      having medium long duration. Girls were 5 times more likely than boys to have
      continuing disease activity. Based on incidence data from the total population of
      the epidemiological study it can be estimated that an additional 100 patients
      with JCA, who were in remission in the beginning of the study, should be included
      in the present cohort. Thus a total of 60% of the patients with JCA had disease
      in remission and 70% were rid of disease activity when reaching adulthood in a
      population based setting. CONCLUSION: The selection of patients in studies of the
      natural history of JCA markedly influences the results, which may be one
      explanation for the divergent views of JCA as both a mild and a progressive
      disease.

PMID- 7738952
TI  - 12-year followup study of epidemic Spanish toxic oil syndrome.
AB  - OBJECTIVE: To determine the longterm clinical and functional outcome among a
      large group of patients with toxic oil syndrome (TOS). METHODS: One hundred
      individuals with onset in 1981 were randomly selected for followup in 1993 from a
      national TOS database. Clinical and laboratory data for 1981 were collected by
      retrospective chart review. Ninety-one survivors were reevaluated in 1993 by
      direct interview, examination, the Health Assessment Questionnaire (HAQ), and the
      visual analog scale (VAS) for pain. A semiquantitative Total Clinical Score (TCS)
      was created to assess relative global outcome in 1993, for comparison with the
      HAQ, and for developing a predictive model based on disease manifestations at
      onset. RESULTS: Fifty-eight percent continue to have symptoms consisting
      predominantly of muscle cramping (60%), fatigue (55%), arthralgias (43%),
      subjective cognitive impairment (44%), psychiatric disease (27%), and soft tissue
      tenderness (22.5%). Severe neuromuscular sequelae, sclerodermatous skin disease,
      or pulmonary hypertension were not detected. The most notable laboratory findings
      at followup were hypercholesterolemia (55%) and hyperglycemia (14.5%). A good
      correlation was demonstrated between both the HAQ and the VAS for pain with the
      TCS. A statistical model indicated that alopecia, Raynaud's phenomenon, and
      sensory neuropathy were predictive of outcome. CONCLUSION: TOS is commonly
      associated with longterm neuromuscular and articular disease. Multiple factors
      implicated in the adaptation to chronic disease may contribute to this morbidity.

PMID- 7738955
TI  - The natural history of juvenile chronic arthritis: a population based cohort
      study. II. Outcome.
AB  - OBJECTIVE: To investigate the outcome in a population based cohort of patients
      with juvenile chronic arthritis (JCA) who were in the process of being
      transferred from pediatric to adult rheumatology care. METHODS: The cohort of
      patients born in 1968 through 1972, recruited from a population based
      epidemiological study in southwestern Sweden, were called to a followup after a
      median disease duration of 7.1 years. The study group consisted of 124 patients
      with a median age of 17.7 years. The disability and discomfort dimensions were
      evaluated using the Childhood Health Assessment Questionnaire (C-HAQ). The impact
      of the disease on social life was evaluated by patients and parents. RESULTS: The
      median C-HAQ disability index was 0.19 with a range from 0 to 2.75 (maximum
      possible score = 3). Sixty percent of the patients indicated some difficulty in
      daily activities. Female sex and a polyarticular disease course were risk factors
      for disability. The strongest determinants for disability were continuing disease
      activity and a positive IgM rheumatoid factor. Social impact of the disease was
      strongly linked to a raised C-HAQ disability index. CONCLUSION: Even in a
      population based study of JCA, which includes many mild cases, the majority of
      patients experienced some difficulty in daily activities when judged by
      themselves. This underlines the necessity to use the patient's own values in
      outcome studies, rather than the physician's. Further development of
      internationally accepted, standardized instruments to evaluate the handicap
      dimension of childhood arthritis is called for.

PMID- 7738956
TI  - von Willebrand factor in juvenile dermatomyositis.
AB  - OBJECTIVE: To evaluate whether plasma von Willebrand factor (vWF) levels are a
      useful indicator of disease activity in juvenile dermatomyositis (DM). METHODS:
      Serum vWF levels were prospectively measured in 15 patients with juvenile DM and
      were compared to serum muscle enzyme levels, muscle strength, and presence of
      extramuscular manifestations. RESULTS: 6/15 active disease periods were
      accompanied by an increase in vWF; 9 were not. Elevated vWF levels did not relate
      to the presence of active skin disease or calcinosis. vWF was not consistently
      related to muscle strength, CPK, or aldolase in the study group. Two patients had
      elevations of vWF in association with viral infections while their DM was
      quiescent. CONCLUSION: An elevated vWF level is often indicative of a disease
      exacerbation in DM, and thus may be helpful in managing difficult cases. However,
      it is not consistently elevated in, nor specific for active disease in DM. It
      therefore cannot be recommended as a routine test in patients with DM. When used,
      results should be interpreted with caution.

PMID- 7738957
TI  - Measuring disability in juvenile dermatomyositis: validity of the childhood
      health assessment questionnaire.
AB  - OBJECTIVE: Physical disability is perhaps the most important outcome of juvenile
      dermatomyositis (JDM). No functional assessment tool has been validated for
      inflammatory myopathies either in children or adults. We studied the measurement
      properties of the Childhood Health Assessment Questionnaire (CHAQ) in children
      with JDM. METHODS: We studied 37 patients followed at the JDM clinic and compared
      the results obtained by the CHAQ to a global disease severity score and
      quantitative muscle strength testing measured by sphygmomanometry (construct
      validity). We also measured the reliability of the CHAQ and its responsiveness to
      clinical change. RESULTS: For the initial measurement of each subject, the
      correlation between disease severity and CHAQ was high [Spearman's correlation,
      (rs = 0.71, p < 0.002)]. Disability as measured by the CHAQ was inversely
      correlated with proximal muscle strength (hip abduction rs = -0.57, p < 0.002;
      shoulder abduction rs = -0.51, p < 0.01) but, as expected, less so with more
      distal muscle strength (knee extension rs = -0.40, p = 0.05; grip strength rs = 
      0.079, p > 0.20). The CHAQ was reliable in subjects who showed no clinical change
      in muscle strength (intraclass correlation coefficient = 0.87) and responsive to
      treatment induced clinical change (responsiveness coefficient = 0.90).
      CONCLUSION: The CHAQ can serve as a valid and sensitive tool in the evaluation of
      functional outcomes in JDM.

PMID- 7738958
TI  - Aortic regurgitation at diagnosis of HLA-B27 associated spondyloarthropathy.
AB  - A 14-year-old boy with a 9 month history of rheumatic symptoms was found to have
      hemodynamically significant aortic regurgitation in association with an HLA-B27
      associated spondyloarthropathy (SpA). Valvular incompetence due to aortitis can
      occur early in the clinical course of pediatric patients with SpA, and careful
      cardiac monitoring is warranted.

PMID- 7738959
TI  - Leukoencephalopathy in a patient taking low dose oral methotrexate therapy for
      rheumatoid arthritis.
AB  - We describe the case of a man who developed a dementing illness with
      leukoencephalopathy while receiving low dose weekly oral methotrexate (MTX)
      therapy for rheumatoid arthritis. The white matter changes seen on magnetic
      resonance imaging and computerized tomogram scan were the same as those seen in
      cases of leukoencephalopathy that have been reported in patients receiving
      intravenous or intrathecal methotrexate. Extensive investigation excluded other
      known causes of white matter disease. Although no improvement either subjectively
      or objectively occurred in his mental status after cessation of treatment with
      MTX, he has remained stable. We believe that this may represent a case of oral
      MTX induced leukoencephalopathy, which has not previously been reported.

PMID- 7738960
TI  - Tophus-like cholesterol nodules in 2 patients with rheumatoid disease.
AB  - We describe 2 patients, both with rheumatoid disease, with tophus-like nodules
      that contained cholesterol crystals. A tophus-like cholesterol nodule had
      developed in a tendon sheath of the left little finger of one. The other
      presented with multiple tophus-like nodules on his left elbow and both forefeet.
      We discuss the etiology and pathogenesis of crystalline deposits of cholesterol.
      Nodules at sites of local pressure in patients with rheumatoid arthritis may be
      deposits of cholesterol crystals.

PMID- 7738961
TI  - Normal pressure hydrocephalus associated with rheumatoid arthritis responding to
      prednisone.
AB  - We describe 2 patients with longstanding rheumatoid arthritis (RA) complicated by
      normal pressure hydrocephalus. After treatment with prednisone, both patients
      improved remarkably with respect to mental status, urinary control, and gait. We
      suggest that normal pressure hydrocephalus may occur as an extraarticular
      manifestation of RA, and studies are warranted to confirm a beneficial response
      to prednisone.

PMID- 7738962
TI  - Lupus panniculitis (profundus) involving the breast: report of 2 cases and review
      of the literature.
AB  - Breast involvement with lupus panniculitis has been infrequently reported. We
      describe 2 cases with breast involvement proven by biopsy to be lupus
      panniculitis. Our review emphasizes the clinical presentation of lupus
      panniculitis with mastitis and its possible clinical similarity to malignancy. In
      addition, other connective tissue diseases and vasculitis with breast involvement
      are noted.

PMID- 7738963
TI  - Coexistence of human immunodeficiency virus infection and systemic lupus
      erythematosus.
AB  - A variety of rheumatic disorders has been reported during the course of human
      immunodeficiency virus (HIV) infection; however, its association with systemic
      lupus erythematosus (SLE) is extremely rare. The effect of HIV infection on CD4
      lymphocytes may ameliorate SLE activity and spur remission. We observed 2
      patients with SLE who later developed HIV infection. Both patients' lupus went
      into remission, and their course was complicated by aseptic necrosis of the bone.
      These findings suggest that HIV infection may have an important effect on the
      natural course of SLE and may also have a pathogenic role in avascular necrosis.

PMID- 7738964
TI  - Polyarteritis nodosa-like vasculitis in human immunodeficiency virus infection.
AB  - Human immunodeficiency virus (HIV) infection can present with musculoskeletal
      syndromes including systemic vasculitis. We describe vasculitis resembling
      polyarteritis nodosa (PAN) in 2 HIV-infected individuals and review reported
      cases to emphasize clinical features. Our patients presented with digital
      gangrene and had vasculitis confirmed by angiography. In reports in the
      literature, patients have presented with digital ischemia and gangrene,
      peripheral neuropathy and constitutional symptoms. The diagnosis has been
      confirmed by angiography and by nerve and muscle biopsy. Treatment with systemic
      corticosteroids has afforded short term benefits to patients; however the
      effectiveness of alternative therapy and longterm prognosis remain unclear.

PMID- 7738965
TI  - Eosinophilic fasciitis with occlusive vasculitis and gangrene of the finger.
AB  - Eosinophilic fasciitis (EF) is characterized by the presence of scleroderma-like
      changes in the skin, inflammation and thickening of the fascia, associated with
      peripheral eosinophilia. Visceral involvement, telangiectasis, Raynaud's
      phenomenon, or gangrene of the digit is very unusual in EF. We describe a patient
      with EF that was accompanied by Raynaud's phenomenon and gangrene of the finger
      due to occlusive vasculitis of small and medium arteries in extremities.

PMID- 7738966
TI  - Giant cell arteritis involving the facial artery.
AB  - Jaw claudication in giant cell (temporal) arteritis (GCA) is believed to be due
      to vasculitic obstruction or stenosis of the arteries supplying the muscles of
      mastication, notably the facial and internal maxillary arteries and their
      branches. However, histologic documentation of this is rarely available because
      GCA is usually diagnosed by temporal artery biopsies. We describe a patient with
      jaw claudication and other clinical features of GCA in whom a facial artery
      biopsy confirmed involvement by GCA.

PMID- 7738967
TI  - Bilateral lower limb gangrene and stroke as initial manifestations of systemic
      giant cell arteritis in an African-American.
AB  - Giant cell arteritis (GCA) is a systemic disease of the elderly that occurs
      infrequently in blacks and seldom has peripheral vascular disease and stroke as
      its presenting major complications. The occurrence of bilateral lower limb
      gangrene and a fatal stroke as manifestations of occult systemic GCA in an
      African-American is such a unique combination of rare occurrences that it
      warrants documentation in the literature.

PMID- 7738968
TI  - Simultaneous clinical manifestations of malignancy and giant cell temporal
      arteritis in a young woman.
AB  - The rare instance of adenocarcinoma of the lung that appeared concurrently with a
      biopsy proven giant cell temporal arteritis in a 45-year-old woman is described.
      The lung cancer (without lymph node metastases) was resected, and the temporal
      arteritis treated with prednisone in the standard dosage regimen. At 36 months
      followup, she was well with no signs of recurrence or metastases of the lung
      cancer, nor any recrudescence of temporal arteritis or polymyalgia rheumatica
      symptoms. This unusual association of lung cancer and temporal arteritis in a
      young woman, most probably a chance occurrence, has not been previously reported.

PMID- 7738969
TI  - Upper limb lymphedema in inflammatory arthropathy.

PMID- 7738971
TI  - Difficulty in detecting reperfusion injury increment in oxidative stress among
      patients with primary Raynaud's phenomenon and systemic sclerosis.

PMID- 7738970
TI  - Cystic distension of the acromioclavicular joint in calcium pyrophosphate
      dihydrate crystal deposition disease.

PMID- 7738972
TI  - RS3PE syndrome associated with advanced ankylosing spondylitis.

PMID- 7738973
TI  - Absence of antineutrophil cytoplasmic autoantibodies in familial Mediterranean
      fever.

PMID- 7738975
TI  - The First International Congress on Smoking Cessation.

PMID- 7738974
TI  - Passive smoking in childhood.
AB  - There is increasing interest in the effects of adult smoking on the health of
      infants and children. Although passive smoking is important in many childhood
      disorders, most attention has been paid to its effects on the respiratory tract
      and on infant mortality. Several studies have reported an increased risk of
      sudden infant death syndrome and respiratory illness in infants of mothers who
      had smoked during pregnancy. Post-natal exposure to passive smoking has been
      found responsible for an increased risk of acute respiratory illness morbidity
      and an increased occurrence of chronic respiratory symptoms. Maternal cigarette
      smoking aggravates asthma symptoms and bronchial responsiveness in children with
      an established diagnosis of the disease, and the possibility that passive smoking
      has a causal role in the aetiology of asthma is currently a matter of growing
      interest. In addition, several studies have shown small but significant
      reductions in lung function values of children exposed to passive smoking.

PMID- 7738976
TI  - Knowledge, attitude and practice towards AIDS among civil servants in Nigeria.
AB  - A study about knowledge, attitude and practice (KAP) towards AIDS was carried out
      amongst 340 randomly selected workers in Benin City in Nigeria using self
      administered questionnaires. Three hundred and thirty (97.1%) of the workers were
      aware of the existence of AIDS but only 50 (14.7%) had the correct knowledge of
      the aetiology of AIDS, and of these 29 (8.5%) had tertiary education. Generally
      there was a good knowledge of the different routes of transmission except for the
      erroneous belief by a high number, 125 (36.8%) and 129 (37.9%) that it could be
      transmitted through sharing of utensils and causal kissing respectively. The
      attitude to AIDS sufferers is poor and 156 (45.9%) actually think they should be
      ostracized. Twenty-one (6.2%) of the respondents still keep multiple sexual
      partners while 142 (41.8%) would willingly use the condom for safer sex. There is
      therefore the need for an intensive and effective health education campaign to
      combat this deadly disease in the country.

PMID- 7738977
TI  - Knowledge and attitudes towards AIDS among primary health care physicians in the
      Asir Region, Saudi Arabia.
AB  - STUDY OBJECTIVES: To assess the knowledge and attitudes towards AIDS among
      practicing physicians in the Asir Region, Saudi Arabia. DESIGN AND PARTICIPANTS:
      A survey was carried out among primary health care (PHC) physicians working in
      the 238 PHC centers in the region. Self administered questionnaires were
      distributed to the 361 physicians working in these centers. Three hundred and
      twenty-eight responded (90.1%) and were included in the study. Non-respondents
      were found not to differ significantly from respondents with regards to sex, age
      and qualifications. MAIN RESULTS: The study revealed several gaps in their
      knowledge regarding AIDS. Of particular concern are those who are to be
      considered at high risk and models of transmission of the disease. CONCLUSIONS:
      These results indicate an urgent need to develop AIDS specific continuing medical
      education program to deal with erroneous ideas to convey the message properly to
      the public.

PMID- 7738978
TI  - The application of hazard analysis critical control point (HACCP) in a flight
      catering establishment improved the bacteriological quality of meals.
AB  - Following an outbreak of salmonellosis affecting 415 passengers on flights in
      1991, the associated flight catering establishment located on a Greek island was
      surveyed for two years. During the first year of the survey, the bacteriological
      quality of food was not satisfactory. In an attempt to maximize food safety for
      crew and passengers the HACCP approach was implemented in 1993. Since its
      application, greatly supported by the management and staff, the bacteriological
      quality of aircraft meals was considerably improved.

PMID- 7738979
TI  - Mental retardation.

PMID- 7738980
TI  - Apolipoprotein E and Alzheimer's disease.

PMID- 7738981
TI  - Meat inspection and education for the 1990s and beyond.

PMID- 7738982
TI  - The environment for the next generation.

PMID- 7738983
TI  - The health of the next generation: health through fitness and sport.

PMID- 7738984
TI  - Public health in the United States.

PMID- 7738985
TI  - Food hygiene systems accreditation scheme.

PMID- 7738986
TI  - Health promotion in the NHS: the Society of Health Education/Promotion
      Specialists.

PMID- 7738987
TI  - Food fraud.

PMID- 7738988
TI  - Induced abortion in Taiwan.
AB  - Induced abortion is widely practised in Taiwan; however, it had been illegal
      until 1985. It was of interest to investigate induced abortion practices in
      Taiwan after its legalization in 1985 in order to calculate the prevalence rate
      and ratio of induced abortion to live births and to pregnancies in Taiwan. A
      study using questionnaires through personal interviews was conducted on more than
      seventeen thousand women who attended a family planning service in Taipei
      metropolitan areas between 1991 and 1992. The reproductive history and sexual
      behaviour of the subjects were especially focused on during the interviews.
      Preliminary findings showed that 46% of the women had a history of having had an
      induced abortion. Among them, 54.8% had had one abortion, 29.7% had had two, and
      15.5% had had three or more. The abortion ratio was 379 induced abortions per
      1,000 live births and 255 per 1,000 pregnancies. The abortion ratio was highest
      for women younger than 20 years of age, for aboriginal women and for nulliparous
      women. When logistic regression was used to control for confounding variables, we
      found that the number of previous live births is the strongest predictor relating
      to women seeking induced abortion. In addition, a significant positive
      association exists between increasing number of induced abortions and cervical
      dysplasia.

PMID- 7738989
TI  - Quality assurance and quality management in the National Health Service.
AB  - This review deals with current views on quality assurance as relevant to both
      health care professionals and health service managers. The concept of quality is
      defined and a brief history of quality in the health service presented. The paper
      then explores political, social and economic factors which govern the provision
      of quality assurance in the modern health service. The possible effects of the
      health service reforms on quality management is discussed.

PMID- 7738990
TI  - Data management: aid to health professionals.

PMID- 7738991
TI  - Managing suicidal behaviour among the prison population.

PMID- 7738992
TI  - Psychiatric targets in 'health of the nation': regional suicide 1974-1990 and
      employment prospects in 1990-1994 in Britain: precursors of failure?
AB  - The psychiatric targets set in 'The Health of the Nation' reflect a fundamental
      change in auditing the psychiatric and social services, and it is argued that
      suicide levels have become 'Paradoxical indicators' of effectiveness. Based upon
      mortality rates between 1974-1990, inter-regional comparative league tables are
      presented. Changes in age and gender patterns, and the accumulative impact of
      unemployment 1990-1994, especially in the more affluent regions, suggest that the
      suicide targets may not be feasible. The implications for the community and
      psychiatric services are briefly discussed.

PMID- 7738993
TI  - Public health in the United States.

PMID- 7738994
TI  - Health education models and food hygiene education.
AB  - Education of food industry personnel in hygiene matters has been recommended as a
      means of improving food handling practices and thus the safety of food. Provision
      has been made within the Food Safety Act 1990 for the making of regulations to
      specify the nature and extent of such training. There is, however, a lack of
      documentary evidence of improvements in food hygiene standards which can be
      directly related to education or training. Evaluations of formal food hygiene
      education courses have identified increased knowledge levels of course
      participants and improvements in the relationship between food industry and
      enforcement personnel. This paper considers the operation of food hygiene
      training in the context of health education theory. Interpretation of this
      suggests that further evaluation of training is warranted prior to programme
      development and that behavioural change might be more likely to occur if the
      settings approach to health promotion were to be adopted in food premises.

PMID- 7738995
TI  - Water poverty.
AB  - Water poverty has become to the 1990s what fuel poverty was to the 1970s and
      1980s. Underlying the growing concern on the issue is, on the one hand, a steep
      rise in the numbers living on poverty level incomes over the past 15 years and on
      the other, increasing difficulties among many poorer households in paying for the
      water that they need. Having briefly outlined current trends in poverty, the
      article explores these difficulties in relation to the price of and methods of
      charging for water and sewerage; the options for helping poorer customers; and
      the consequences of non-payment. It will focus in particular on the implications
      for health of two controversial issues: compulsory volumetric metering and water
      disconnections.

PMID- 7738996
TI  - Tobacco advertising.

PMID- 7738997
TI  - A comparative study of generalised obesity and anatomical distribution of
      subcutaneous fat in adult white and Pakistani migrant males in Peterborough.
AB  - Obesity can be defined in two main ways--generalised obesity (measured as Body
      Mass Index (BMI)) and anatomical distribution of adiposity. A comparative study
      of generalised obesity (body mass index) and the anatomical distribution of
      subcutaneous fat in adult White and Pakistani migrant males was carried out in
      Peterborough. No significant difference in the prevalence of obesity as measured
      by the BMI was observed between Whites and Pakistani migrants. The mean BMI
      values were similar in both ethnic groups. However, Pakistanis had significantly
      more truncal fat compared with Whites whereas the latter group had more upper
      extremity fat compared with the former. No significant difference was observed in
      the amount of fat deposited on the lower extremities between the two ethnic
      groups. The Pakistanis also had significantly more total (sum of all skinfolds)
      subcutaneous fat compared with Whites. These preliminary results clearly indicate
      that there is a tendency for accumulation of truncal adiposity in Asians of
      Pakistani origin compared with Whites irrespective of the level of generalised
      (BMI) obesity. The health implications of body fat patterning on non-insulin
      dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD) are well
      known. It is possible that the pattern of fat distribution observed in migrant
      Pakistani males in this study exists in other migrant groups originating from the
      Indian subcontinent. This pronounced truncal distribution of body fat could be
      one of the risk factors predisposing migrant Asians in the UK to develop NIDDM
      and CHD irrespective of their BMI. Future epidemiological studies should lay more
      emphasis on morphological fat patterning rather than BMI in Asian migrants in the
      UK.

PMID- 7738998
TI  - Social and dietary factors associated with obesity in university female students
      in United Arab Emirates.
AB  - A cross-sectional study on 215 university female students aged 18-30 years was
      undertaken in 1993 to examine some factors associated with obesity among this
      group of females. Based on Body Mass Index (BMI), (wt/ht2), 19% of females were
      overweight and 9.8% were obese. The proportion of obesity was the highest in
      females aged 18 years (31%) compared to those aged 19 and 20 years and above
      (23.8% and 27.6%, respectively). Although there was no significant association
      between obesity and social factors studied, the prevalence of obesity was higher
      in non-national, those with educated mothers, having no housemaid, and having a
      family history of obesity. Skipping meals and snacks had no significant
      association with obesity, however, obesity was more prevalent among females who
      did not skip lunch. In contrast, females who ate afternoon snacks and supper were
      more likely to be obese than females who skipped these events. Median BMI for
      university females was higher than that reported in USA for the same age group,
      while median values for weight and mid-arm circumference for females studied were
      similar to that reported in their counterparts in Western countries.

PMID- 7738999
TI  - Metabotropic glutamate receptors: novel targets for drug development.

PMID- 7739000
TI  - Expedient method for the solid-phase synthesis of aspartic acid protease
      inhibitors directed toward the generation of libraries.

PMID- 7739001
TI  - Measuring diversity: experimental design of combinatorial libraries for drug
      discovery.
AB  - Screening synthetic combinatorial libraries, such as mixtures of oligo(N
      substituted)glycines, facilitates rapid drug lead discovery and optimization by
      vastly increasing the number of candidate molecules made and tested. Discovery
      efficiency and productivity can be further improved by using experimental design
      to maximize molecular diversity for a given library size or to bias the library
      with key features for a specific receptor. We describe new methods to quantify
      molecular diversity using descriptors that characterize lipophilicity, shape and
      branching, chemical functionality, and specific binding features. Experimental
      design methods select sets of side chains that are diverse in these properties,
      and "flower plots" allow the diversity to be graphically compared. We also
      quantify the overall diversity accessible to different families of combinatorial
      chemistry.

PMID- 7739002
TI  - Design, synthesis, and evaluation of A/C/D-ring analogs of the fungal metabolite
      K-76 as potential complement inhibitors.
AB  - The terpenoid 6,7-diformyl-3',4',4a',5',6',7',8',8a'-octahydro-4,6',7'-trihydrox
      y-2',5',5', 8a'-tetramethylspiro[1'(2'H)-naphthalene-2(3H)-benzofuran] (1a; K
      76), a natural product of fungal origin, and its monocarboxylate sodium salt 1c
      (R = COONa; K-76COONa) inhibit the classical and alternative pathways of
      complement, and 1c was shown to inhibit the classical pathway at the C5
      activation step. In an attempt to elucidate the essential pharmacophore of 1a,c,
      the natural product was used as a "topographical model" for the design of partial
      analogs retaining the desired complement inhibiting potency. Therefore, A/C/D
      ring analogs have been synthesized, as shown in Scheme 1 using 3-methoxyphenol
      (3) and limonene chloride (5) as starting materials, which contain functional
      groups similar to those found on the natural product. The use of (4R)-(+)- and
      (4S)(-)-limonene chloride (5a,b, respectively) provided two series of compounds
      differing in the stereochemistry of the C-4 chiral center (limonene moiety
      numbering). The in vitro assay results of the inhibition of anaphylatoxin
      production and classical complement-mediated hemolysis revealed that 7-carboxy-2
      (R,S)-methyl-2-(1'-methylcyclohexen-(4'R)-yl)-4-met hoxybenzofuran (13a) and 7
      carboxy-2-(R,S)-methyl-2-(1'-methylcyclohexen-(4'S)-yl)-4-met hoxybenzofuran
      (13b) were active in the same range of concentrations as the natural product.

PMID- 7739003
TI  - Evaluation of physicochemical parameters important to the oral bioavailability of
      peptide-like compounds: implications for the synthesis of renin inhibitors.
AB  - A series of radiolabeled compounds related to renin inhibitor structures was
      synthesized to represent a range of physicochemical properties. These compounds
      were tested in assays for intestinal absorption and hepatic clearance in order to
      define parameters conducive to optimizing bioavailability. In general, compounds
      with higher lipophilicity were better absorbed from the intestine. Absorption may
      also be dependent on molecular charge, as compounds with ionizable functionality
      were less well-absorbed than neutral compounds. Neutral compounds showed some
      dependency on molecular weight, with smaller compounds exhibiting better
      absorption. While uptake into hepatic cells was rapid regardless of partition
      coefficient or molecular weight, rate of appearance in bile was dependent on the
      molecular weight of the compounds.

PMID- 7739004
TI  - Synthesis and in vitro evaluation of 4-substituted N-(1,1-dimethylethyl)-3-oxo-4
      androstene-17 beta-carboxamides as 5 alpha-reductase inhibitors and
      antiandrogens.
AB  - 4-Substituted N-(1,1-dimethylethyl)-3-oxo-4-androstene-17 beta-carboxamides with
      the hydroxy (OH) 3d, mercapto (SH) 3e, chloro (Cl) 3f, and bromo (Br) 3g
      substituents at the 4-position were prepared in a two-step sequence with overall
      yields of 21%, 27%, 41%, and 37%, respectively. Compounds 3d-g showed weak
      inhibitory activity on human type I 5 alpha-reductase (IC50 > or = 700 nM) while
      they had intermediate inhibitory activity on human type II 5 alpha-reductase at
      IC50S of 172, 437, 192, and 387 nM, respectively. In androgen-sensitive Shionogi
      cells, the inhibition of dihydrotestosterone (DHT) stimulatory action on the
      proliferation of the androgen-sensitive cancer cells by all four compounds was
      high at IC50S of 170-279 nM compared with 117 nM for hydroxyflutamide. The
      present data show compounds having both moderate inhibition of human type II 5
      alpha-reductase activity and relatively potent antiandrogenic action, two
      beneficial characteristics in the therapy of androgenic-sensitive diseases.

PMID- 7739005
TI  - 2-Aralkynyl and 2-heteroalkynyl derivatives of adenosine-5'-N-ethyluronamide as
      selective A2a adenosine receptor agonists.
AB  - A series of new 2-aralkynyl and 2-heteroaralkynyl derivatives of NECA were
      synthesized and studied in binding and functional assays to assess their potency
      for the A2a compared to A1 adenosine receptors. Compounds bearing an aromatic or
      heteroaromatic ring, conjugated to the triple bond, showed generally weaker
      activity at the A2a receptor and lower selectivity (A2a vs A1) than the
      alkylakynyl derivatives previously reported. However, the (4-formylphenyl)
      ethynyl derivative 17 showed affinity in the low nanomolar range and high
      selectivity (about 160-fold) for the A2a receptor. The presence of heteroatoms
      improved vasorelaxant activity, the 2-thiazolylethynyl derivative 30 being the
      most potent in the series. Introduction of methylene groups between the triple
      bond and the phenyl ring favored the A2a binding affinity, and the 5-phenyl-1
      pentynyl derivative 24 was found to be highly potent and selective (about 180
      fold) at A2a receptors. With regard to antiplatelet activity, the presence of
      aromatic or heteroaromatic rings decreased potency in comparison with that of
      NECA and of N-ethyl-1'-deoxy-1'-(6-amino-2-hexynyl-9H-purin-9-yl)-beta-D-ribofura
      nuronamide (HENECA). Introduction of a methylene group was effective in
      increasing antiaggregatory potency only when this group is linked to a heteroatom
      (31-35). From these data and those previously reported, the structure-activity
      relationships derived for the 2-alkynyl-substituted ribose uronamides would
      indicate that potentiation of A2a receptor affinity could be obtained by aromatic
      rings not conjugated with the triple bond or by heteroaromatic groups. As for A2a
      receptors on platelets, the presence of aromatic rings, either conjugated or
      unconjugated to the triple bond, is detrimental for the antiaggregatory activity.
      However, the introduction of polar groups alpha to the triple bond strongly
      increases the potency when steric hindrance is avoided. Some of the compounds
      included in this series retain interesting vasodilating properties and merit
      further investigation for their potential in the treatment of cardiovascular
      disorders.

PMID- 7739007
TI  - Antitumor activity of 9(R)-dihydrotaxane analogs.
AB  - A novel reduced taxane, 13-acetyl-9(R)-dihydrobaccatin III (1) has been isolated
      from Taxus canadensis. The selective C-13 deacetylation of this isolate has
      allowed for the preparation of a wide variety of 9(R)-dihydrotaxane analogs. In
      general, this series has shown greater stability and water solubility than the 9
      carbonyl series while retaining antimicrotubule and tumor cell cytotoxicity
      activities relative to taxol. Placement of polar functionalities at the C-7
      position results in loss of activity whereas alkylation or acylation of either C
      7 or C-9 hydroxyl groups ameliorate the activity.

PMID- 7739006
TI  - Synthesis and antiinflammatory activity of certain 5,6,7,8-tetrahydroquinolines
      and related compounds.
AB  - Modification of some 8-benzylidene-5,6,7,8-tetrahydroquinolines, which have good
      antiulcer activity, led to three distinct classes of compounds with good in vivo
      antiinflammatory activity. Initial efforts led to a series of alkenes derived
      from 5,6,7,8-tetrahydroquinolines substituted at the 8-position. A second
      approach concentrated on replacing the CH linkage of these 8-benzylidene
      substituted compounds with other spacer groups and increasing the size of the
      cycloalkyl ring from a six- to seven-membered ring, which provided 6,7,8,9
      tetrahydro-5H-cyclohepta[b]pyridine analogues. Finally, the substituent was
      switched from the cycloalkyl ring to the 2-position of the pyridine ring.
      Variation of the 2-substituent was also examined. Optimal antiinflammatory
      activity after oral administration was found in both the rat carrageenan paw
      edema and rat developing adjuvant arthritis models with 2-substituted 6,7,8,9
      tetrahydro-5H-cyclohepta[b]pyridines, and of particular interest was 27 (WY
      28342).

PMID- 7739008
TI  - Antitumor imidazotetrazines. 32. Synthesis of novel imidazotetrazinones and
      related bicyclic heterocycles to probe the mode of action of the antitumor drug
      temozolomide.
AB  - A series of new imidazo[5,1-d]-1,2,3,5-tetrazinones with additional hydrogen
      bonding or ionic substituents at the 8-carboxamide position of the antitumor
      drugs temozolomide (1) and mitozolomide (2) has been prepared. None of these
      compounds were significantly more cytotoxic in vitro against the mouse TLX5
      lymphoma than the lead structures. Molecular modeling techniques have been used
      to design benzo- and pyrazolo[4,3-d]-1,2,3-triazinones bearing carboxamide groups
      in appropriate positions which are isosteric with temozolomide and mitozolamide
      but which cannot ring open to alkylating species. As predicted, these compounds
      have no inhibitory properties against human GM892A or Raji cell lines in vitro.
      Temozolomide and the spermidine-temozolomide conjugate 28 preferentially
      methylate guanines within guanine-rich sequences in DNA, but no experimental
      evidence has been found to support the hypothesis that such regions are involved
      in catalyzing the ring opening of the imidazotetrazinone prodrugs to their active
      forms.

PMID- 7739009
TI  - Phosphodiesterase type IV inhibition. Structure-activity relationships of 1,3
      disubstituted pyrrolidines.
AB  - The synthesis of 1,3-disubstituted pyrrolidines 2 and their activities as type IV
      phosphodiesterase (PDE) inhibitors are described. Various groups were appended to
      the nitrogen of the pyrrolidine nucleus to enable structure-activity
      relationships to be assessed. Groups which render the pyrrolidine nitrogen of 2
      nonbasic yielded potent PDE-IV inhibitors. Analogs of amides, carbamates, and
      ureas of 2 were synthesized to determine the effects that substitution on these
      functional groups had on PDE-IV inhibitor potency. The structural requirements
      for PDE-IV inhibitor potency differed among the three classes. A representative
      amide, carbamate, and urea (2c,d,h) were shown to be > 50-fold selective for
      inhibiting PDE-IV versus representative PDEs from families I-III and V.
      Furthermore, these same three inhibitors demonstrated potent functional activity
      (IC50 < 1 microM) by inhibiting tumor necrosis factor-alpha (TNF-alpha) release
      from lipopolysaccharide (LPS)-activated purified human peripheral blood monocytes
      and mouse peritoneal macrophages. These compounds were also tested orally in LPS
      injected mice and demonstrated dose-dependent inhibition of serum TNF-alpha
      levels.

PMID- 7739010
TI  - Characterization of a class of peptide boronates with neutral P1 side chains as
      highly selective inhibitors of thrombin.
AB  - Z-D-Phe-Pro-boroMpg-OPin (9a)1,2 has been shown previously to be a highly
      specific inhibitor of thrombin in spite of lacking an arginine-like guanidino
      group at the P1 site. A range of compounds have been synthesized based upon this
      lead compound, varying the neutral side chain at the P1 site. Of the 20 examples
      based upon the structures at P2 and P3 of Z-D-X-Pro (X being Phe or beta,beta
      diphenylalanine), all were found to be effective inhibitors of thrombin (Ki's
      between 10 and 100 nM). Furthermore all exhibited a high specificity toward
      thrombin having values for a Ki(trypsin)/Ki(thrombin) ratio of between 10- and
      100-fold. High ratio values were found for a number of the compounds tested
      against a range of serine proteinases (plasmin, factor Xa, kallikrein, urokinase,
      protein Ca, chymotrypsin, elastase, and cathepsin G). As far as potency toward
      thrombin, compounds containing the methoxypropyl group at P1 were favored over
      those with a methoxy grouping on a shorter alkyl chain (8) or without the methoxy
      group (1-5). The compounds display potent anticoagulant activity with values for
      18 in thrombin time of 0.63 microM and in activated partial thromboplastin time
      of 2.0 microM. 11B NMR has been used to confirm interaction of the boron atom
      with the active site. From the high specificity shown with all the compounds we
      propose that the compounds, constitute a new class of thrombin inhibitors.

PMID- 7739011
TI  - Probes for narcotic receptor-mediated phenomena. 20. Alteration of opioid
      receptor subtype selectivity of the 5-(3-hydroxyphenyl)morphans by application of
      the message-address concept: preparation of delta-opioid receptor ligands.
AB  - Derivatives of racemic and optically active 5-(3-hydroxyphenyl)-2-methylmorphan
      (5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonane, 1) were synthesized
      containing additional aromatic moieties, as an application of the message-address
      concept targeted at producing delta-opioid receptor selective ligands. In vitro
      radioreceptor binding studies in rat brain revealed that both of the parent
      enantiomers, (-)- and (+)-1, had a high affinity for the mu-opioid receptor (21
      nM), a slight affinity for kappa 1-opioid receptors (approximately 800-900 nM),
      and less than 1000 nM affinity for the delta-opioid receptor (mu/delta IC50 ratio
      of < 0.02 for both). A derivative of (-)-1 containing an indole moiety fused at
      the C6-C7 position of the phenylmorphan nucleus, (-)-11, displayed a > 180-fold
      increase in affinity for the delta-opioid receptor with an IC50 value of 6 nM.
      The parent compound (-)-1 had only 26% agonist activity at 30 microM in the mouse
      vas deferens (delta) bioassay, whereas compound (-)-11 had an IC50 of 393 nM in
      this preparation, indicating the importance of the indole moiety in imparting
      delta-opioid agonist activity to the phenylmorphan (-)-11. A structure-activity
      relationship (SAR) study of N-alkyl derivatives of the racemic nor 11 indicated
      similarities between the interaction of various derivatives with the mu- and
      delta- but not the kappa 1-opioid receptor. As studies on the molecular basis of
      the interaction of opioid ligands with their respective receptors continue to
      gain momentum, the SAR data described herein for the synthetic phenylmorphans
      will prove useful for further studies.

PMID- 7739012
TI  - Synthesis of cluster galactosides with high affinity for the hepatic
      asialoglycoprotein receptor.
AB  - High-affinity ligands for the asialoglycoprotein receptor, which is uniquely
      localized on the parenchymal liver cell and recognizes oligoantennary
      galactosides, might be utilized as homing device to specifically target drugs or
      genes to parenchymal liver cells. In the present study, the synthesis of
      galactose-terminated triantennary glycosides, provided with various spacers
      between the beta-galactopyranosyl moieties and the branching point of the
      dendrite, is described. N-[Tris[[(methylthio)methoxy]methyl]methyl]-N alpha-[1-(6
      methyladipy)]glycinamide (3b) was glycosylated with monogalactosyl derivatives,
      containing propanediol or ethylene glycol units as hydrophilic spacer moieties,
      to yield the corresponding cluster galactosides. To determine the affinity of the
      cluster galactosides for the asialoglycoprotein receptor, we have performed
      competition studies of [125I]ASOR binding, a specific ligand for the
      asialoglycoprotein receptor, to isolated parenchymal cells. The affinity for the
      asialoglycoprotein receptor significantly increased with increasing spacer
      length. N-[[[Tris-O-(beta-D-galactopyranosyl)-3,6,9-trioxaunde-
      canoxy]methoxy]methyl]-N-alpha-[1-(6-methyladipyl)]glycinami de (4e), a cluster
      galactoside provided with a 20 A spacer, possessed an at least 2000-fold higher
      affinity for the receptor than N-[[tris-O-(beta-D-galactopyranosyl)methyl]methyl]
      N alpha-[1-(6- methyladipyl)]glycinamide (4a), a cluster galactoside lacking the
      spacer. It is concluded that vicinal galactosyl moieties within a cluster
      galactoside are more optimal recognized by the galactose binding sites of the
      asialoglycoprotein receptor upon proper spacing. The most potent galactoside,
      TG(20A), may constitute an attractive targeting device for the specific delivery
      of drugs and/or genes to the parenchymal liver cell.

PMID- 7739013
TI  - Enantiomers of diastereomeric cis-N-[1-(2-hydroxy-2-phenylethyl)- 3-methyl-4
      piperidyl]-N-phenylpropanamides: synthesis, X-ray analysis, and biological
      activities.
AB  - (+/-)-cis-N-[1-(2-Hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-
      phenylpropanamide (1) is a mixture of four stereoisomers [(2S,3R,4S)-1a,
      (2R,3R,4S)-1b, (2R,3S,4R)-1c, and (2S,3S,4R)-1d], which together constitute two
      diastereoisomeric pairs of optical isomers. These four stereoisomers were
      prepared from optically active intermediates of known absolute configuration by
      procedures which had no effect on the configurations of the piperidine 3- and 4
      carbons. The configuration of the phenylethyl 2-carbon in the final products was
      determined by X-ray analysis of (2S,3S,4R)-1d. A 1H NMR comparison of the final
      products to ohmefentanyl established that the racemic pair previously known as
      ohmefentanyl was a mixture of (2S,3R,4S)-1a and (2R,3S,4R)-1c. The individual
      activities of 1a, 1b, 1c, and 1d were evaluated in a variety of binding and
      pharmacological assays. The binding data revealed that isomers 1b and 1c had the
      highest affinity and selectivity for the mu site labeled with [3H]DAMGO. In
      contrast, the four isomers displaced [3H]etorphine in the order 1a approximately
      1b > 1c approximately 1d. Evaluation of the four isomers on the mouse vas
      deferens (MVD) preparation revealed a potency order of 1a > 1b > 1c > 1d with
      concentrations of 1a and 1b in the femtomolar range causing inhibition.
      Experiments using the antagonists naltrexone (mu), ICI 174864 (delta), and
      norbinaltorphimine (kappa) demonstrated that the effects of 1a were mediated
      largely by the mu receptor while both delta and kappa agonist effects contributed
      to the actions of 1b and 1c. Isomer 1d acted as a weak mu antagonist in the MVD
      preparation. The same potency order was observed in a mouse analgesic assay and a
      rhesus monkey single dose suppression study. From the latter study the potency of
      1a was estimated to be 20,000-50,000 times that of morphine, making this isomer
      one of the most potent opiates known. In the rhesus monkey study, isomer 1d
      failed to substitute for morphine and seemed to exacerbate withdrawal at doses of
      0.6, 3.0, and 6.0 mg/kg. On the basis of the mouse data, isomer 1a was 21,000
      times more potent than 1d, whereas isomers 1b and 1c were similar in their opiate
      activity in vivo. Using the optical isomers of cis-3-methylfentanyl as reference
      compounds, we analyzed the effects on the pharmacological activities of
      introducing a phenylethyl 2-hydroxyl group into the molecule.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7739014
TI  - In vitro muscarinic activity of spiromuscarones and related analogs.
AB  - The cholinergic hypothesis of Alzheimer's disease suggests that cholinergic
      agonists may have therapeutic potential for treating the attendant memory
      deficits of the disease. As part of a program aimed at preparing metabolically
      stable, nonquaternary analogs of muscarone, 1-oxa-2,8-dimethyl-8
      azaspiro[4.5]decan-3-one, 2a, and related analogs have been synthesized and their
      in vitro muscarinic activity evaluated. The synthetic strategy in the formation
      of the 1-spiro[4.5]decan-3-one ring system of 2a involved cyclization of the diol
      4 in the presence of Nafion-Hg. The spiromuscarone 2a was found to displace
      [3H]Oxo-M binding with a Ki value of 7 nM. Affinities of the oxime and hydrazone
      analogs of 2a were lower than 2a. The compounds in these series were partial
      muscarinic agonists as demonstrated by stimulation of phosphatidyl inositol
      hydrolysis assay, with 2a showing the highest intrinsic intrinsic activity (60%
      as compared with carbachol). The results from this study indicate that an exo
      double bond at the C-3 position is essential for the receptor binding.

PMID- 7739015
TI  - Phosphonates and phosphinates: novel leaving groups for benzisothiazolone
      inhibitors of human leukocyte elastase.
AB  - A novel class of alkyl and aryl phosphonate and phosphinate acid-based leaving
      groups has been developed for utilization in the synthesis of benzoisothiazolone
      (BIT) inhibitors of human leukocyte elastase (HLE). A number of BITs were
      synthesized with phosphonate and phosphinate acid-based leaving groups and were
      found to be potent inhibitors of HLE. Compound 3c with a diethyl phosphonate
      leaving group is the most potent inhibitor synthesized in this series with Ki* =
      0.035 nM and ED50 = 2.0 mg/kg.

PMID- 7739016
TI  - Absolute configuration of (+)-[fluoro(hydroxyphenylphosphinyl)methyl]-phosphonic
      acid, a specific inhibitor of Na(+)-gradient-dependent Na(+)-phosphate
      cotransport across renal brush border membrane, by X-ray crystallographic
      analysis of its (-)-quinine salt.
AB  - Racemic [fluoro(hydroxyphenylphosphinyl)methyl]phosphonic acid (1) and its
      individual enantiomers [(+), 98% ee; (-), 67% ee] were previously shown to
      inhibit Na(+)-gradient-dependent Na(+)-phosphate cotransport across renal brush
      border membrane, without measurable stereospecificity. Resolution of 1 was
      effected by fractional recrystallization of its (-)-quinine salts. The more
      levorotatory, diquinine product 2, corresponding to (+)-1, has now been analyzed
      by X-ray crystallography and found to be composed of the S enantiomer of 1. This
      result confirms the absence of stereochemical preference in inhibition of the
      cotransporter by the enantiomers of 1 and provides the first absolute
      configuration assignment of an asymmetrical alpha-halomethylene pyrophosphate
      analogue.

PMID- 7739017
TI  - Astroviruses.

PMID- 7739018
TI  - Immunoglobulin and non-immunoglobulin components of human milk inhibit
      Clostridium difficile toxin A-receptor binding.
AB  - Clostridium difficile is isolated from the intestinal tracts of > 50% of healthy
      infants. The mechanism by which intestinal colonisation of infants by toxigenic
      C. difficile is generally asymptomatic is unknown but may reflect the presence in
      human milk of neutralising activity against C. difficile toxin A. On this basis,
      the ability of human milk to inhibit the binding of toxin A to a purified hamster
      brush border membrane receptor was determined. Ten milk samples from healthy
      volunteers in various stages of lactation inhibited the binding of toxin A to the
      receptor by an average of 90%. Heating and dialysis did not significantly alter
      the inhibitory activity of any of the milk samples. Human milk protected adult
      hamsters against a lethal challenge with toxin A but had no effect on the
      cytotoxic activity of the toxin. SDS-PAGE and ligand blot analyses showed that
      there were at least four distinct factors in human milk that specifically bound
      toxin A. Thiophilic adsorption chromatography was used to separate immunoglobulin
      from non-immunoglobulin components of human milk. IgA was the only immunoglobulin
      detected in human milk and > 90% of this immunoglobulin was recovered after
      purification by thiophilic adsorption. Both the unbound non-immunoglobulin and
      bound immunoglobulin fractions of human milk inhibited the binding of toxin A to
      the purified receptor. These results suggest that human milk may be important in
      protecting infants against C. difficile-associated intestinal disease.

PMID- 7739019
TI  - Studies on the genesis of Vibrio cholerae O139: identification of probable
      progenitor strains.
AB  - Four lines of evidence suggest that the recent outbreak strains of Vibrio
      cholerae O139 could have emerged from serogroup O1 strains typified by isolates
      M01 and M0477 described in this paper, which are neither truly classical nor
      truly E1 Tor in their biotype attributes. Firstly, like all O139 isolates, these
      O1 strains, isolated in Madras during and before the O139 outbreak, were
      resistant not only to polymyxin B but also to all biotype-specific choleraphages,
      i.e. classical phage phi 149 and E1 Tor phages e4 and e5. Secondly, the
      restriction fragment pattern (RFP) polymorphism displayed by these strains for
      the cholera toxin (ctx) gene, were identical with those produced by O139 isolates
      but were different from those of O1 type strains, namely V. cholerae 569B
      (classical) and V. cholerae MAK757 (E1 Tor). Thirdly, all the O139 isolates and
      the two O1 isolates carried an identical large number of copies of cholera toxin
      gene in their chromosomes. Finally, the outer-membrane protein profiles of
      strains M01 and M0477 were identical to those of O139 isolates but were different
      from those displayed by strains 569B and MAK757.

PMID- 7739020
TI  - Association of Aeromonas spp. with travellers' diarrhoea in Finland.
AB  - The association of Aeromonas spp. with travellers' diarrhoea was studied among
      978 Finnish tourists travelling to Morocco in winter (n = 398) and autumn (n =
      580) in 1989. Fifty-five isolates from diarrhoeal patients with (n = 16) or
      without (n = 39) a recent travelling history in a developing country were also
      included. In Morocco, Aeromonas spp. were isolated from 8.7% of patients with
      diarrhoea and from 1.4% of non-diarrhoeal tourists (p < 0.001). Aeromonas spp.
      were found as the sole pathogen in 5.5% of patients (p < 0.001). Diarrhoea with
      multiple pathogens, including Aeromonas spp., was found in 3.1% of patients.
      Species identification by phenotypic and genotypic methods indicated that A.
      veronii biotype sobria (hybridisation group HG 8/10) and A. caviae (HG 4) were
      the most common Aeromonas spp. associated with travellers' diarrhoea. A.
      hydrophila (HG 1) and A. caviae (HG 4) were common in patients acquiring
      diarrhoea in Finland. Ribotyping of strains within a species showed that all
      strains had different ribotypes although the tourists were infected during the
      same trip. This study suggested that only certain Aeromonas spp. were commonly
      found in travellers' diarrhoea. However, the causative role of those species is
      unclear.

PMID- 7739021
TI  - Free secretory component and lactoferrin of human milk inhibit the adhesion of
      enterotoxigenic Escherichia coli.
AB  - The non-immunoglobulin component of human milk responsible for the inhibition of
      Escherichia coli cell adhesion (haemagglutination) mediated by colonisation
      factor antigen 1 (CFA1) was determined by chromatographic fractionation of human
      whey proteins with Sephadex G-200, DEAE cellulose and heparin-sepharose. Pure
      free secretory component (fSC) and pure lactoferrin (Lf) were isolated and both
      compounds inhibited the haemagglutination induced by E. coli CFA1+. The lowest
      concentrations of purified fSC and Lf able to inhibit the haemagglutination
      induced by E. coli strain TR50/3 CFA1+ were 0.06 mg/ml and 0.1 mg/ml
      respectively. Commercially available lactoferrin from human milk and transferrin
      from human serum, which has a great structural analogy to lactoferrin, also
      inhibited the haemagglutination. The lowest concentrations of the commercial
      lactoferrin and transferrin able to inhibit the haemagglutination induced by E.
      coli TR50/3 CFA1+ were 0.03 mg/ml and 0.4 mg/ml, respectively. These results
      indicate that fSC and Lf may be important non-specific defence factors against
      enterotoxigenic E. coli infections.

PMID- 7739022
TI  - Temperature-dependent protein and lipopolysaccharide expression in clinical
      Aeromonas isolates.
AB  - Clinical isolates of Aeromonas were grown at eight different temperatures from 10
      degrees C to 40 degrees C. Whole cell lysates were examined by SDS-PAGE and major
      temperature-dependent changes to both protein and lipopolysaccharide (LPS)
      profiles were identified. Cells grown at the higher temperatures (37 degrees C
      and 40 degrees C) produced abundantly a protein of c. 60 kDa which was not
      detected at the lower temperatures. Temperature-dependent expressions of other
      proteins were also noted but these were more variable among the isolates. An
      effect of temperature on expression of lipopolysaccharides was also noted in that
      some strains produced significantly less O-polysaccharides at the higher
      temperatures. After fractionation of cells, major differences in the expression
      of cell envelope and outer-membrane proteins between cells grown at low and high
      temperatures were noted although no unifying patterns could be discerned. Such
      growth temperature-induced changes in the cell envelope constituents have not
      been described previously for Aeromonas isolates from man.

PMID- 7739023
TI  - Virulence and other phenotypic characteristics of urinary isolates of cysteine
      requiring Escherichia coli.
AB  - Urinary isolates of cysteine-requiring Escherichia coli were found to be
      generally lacking in virulence factors commonly associated with uropathogenic
      strains. The proportion of auxotrophic strains showing type-1 fimbriation,
      haemolysin production, motility and sensitivity to normal human serum was
      significantly less than that of a comparable number of urinary isolates of
      prototrophic E. coli, although the proportion in both groups possessing K1
      antigen was similar. Furthermore, the biotyping and serogrouping of these and
      other strains from systemic infections demonstrated a high degree of phenotypic
      diversity. This is further evidence that infection with these auxotrophs results
      from a combination of decreased host resistance and a physiological condition
      conducive to the random selection of these auxotrophs in vivo.

PMID- 7739024
TI  - No difference in enterotoxin production among Staphylococcus aureus strains
      isolated from blood compared with strains isolated from healthy carriers.
AB  - The production of enterotoxin A, B, C and D by 196 Staphylococcus aureus strains
      isolated from blood cultures and 95 strains from nasal carriers was investigated.
      Half of the bacteraemia strains were from patients who died with or because of
      their infection, the other half from patients who survived. The nasal strains
      were selected to match the bacteraemia strains regarding phage types. Overall,
      30.6% of the bacteraemia strains and 40.0% of the nasal strains produced
      enterotoxins; enterotoxins B and C were the toxins produced most frequently in
      both groups. A similar incidence and pattern of enterotoxin production was found
      among the bacteraemia strains of S. aureus regardless of acquisition of the
      infection, the portal of entry, presence or absence of endocarditis and outcome
      of the infection. Thus, the concept that the enterotoxins play an important role
      in staphylococcal infections, apart from the diseases caused by the toxins per se
      such as food poisoning and toxic shock syndrome, cannot be substantiated by the
      results of the present study.

PMID- 7739025
TI  - In-vitro hepatotoxic factor in Helicobacter hepaticus, H. pylori and other
      Helicobacter species.
AB  - Several inbred strains of mice in closed breeding colonies were found to have
      spiral-shaped bacteria associated with active, chronic hepatitis. A new species
      of Helicobacter, H. hepaticus, was isolated from the infected livers of some
      strains of mice. Other strains of mice were colonised with H. hepaticus in the
      caecum and colon, but not the liver. Filtersterilised supernatant fluid from five
      strains of H. hepaticus was tested in a mouse liver cell line (ATCC no. CCL 9.1)
      for cytotoxic activity. All strains produced a toxic factor causing morphological
      changes in the cells at dilutions up to 1 in 1000. Toxicity was observed after
      exposure to the supernatant fluid for 48-72 h. Other Helicobacter spp. that also
      produced the cytopathic effect (CPE) in the liver cell line were H. felis, H.
      acinonyx, H. pylori and one strain of H. mustelae. "Helicobacter rappini" and H.
      muridarum did not cause CPE in the liver cells. The soluble factor was stable at
      4 degrees C for up to 3 months. It was also stable at 56 degrees C for 30 min,
      but was inactivated by boiling for 15 min. It was inactivated by incubation with
      trypsin. A partially purified preparation of the cytotoxin had a mol. wt of c.
      100,000 and did not have urease activity. The cytotoxin produced by H. hepaticus
      did not cause vacuole formation in HeLa cells.

PMID- 7739026
TI  - Comparative antibody responses and protection in mice immunised by oral or
      parenteral routes with influenza virus subunit antigens in aqueous form or
      incorporated into ISCOMs.
AB  - The total and subclass antibody responses of mice and protection of these animals
      against live influenza A/Sichuan/2/87 virus challenge infection were determined
      after immunisation with homologous A/Sichuan/87 aqueous or ISCOM-formulated
      surface glycoprotein subunit antigens administered by either the oral or
      intramuscular routes. The results show that the greatest systemic and local
      antibody responses were elicited in mice immunised with A/Sichuan ISCOMs by the
      intramuscular route; protection against homologous virus challenge was also
      effective in these animals, particularly after two doses of the vaccine. However,
      relatively high immune responses and protection were also elicited by the
      A/Sichuan/87 ISCOM vaccine administered orally. Immunisation of mice by the
      intramuscular route resulted in levels of serum IgG2a subclass antibody
      significantly greater than those induced by the same preparation given by the
      oral route, or by the aqueous A/Sichuan/87 subunit antigen preparation
      administered by either route. The findings indicate that the ISCOM delivery
      system can be used for immunisation by the oral route, although in mice, under
      the conditions used, this strategy compares unfavourably with the intramuscular
      route in terms of both local and systemic immune responses and protection against
      homologous challenge virus infection.

PMID- 7739027
TI  - Killing of methicillin-resistant Staphylococcus aureus by low-power laser light.
AB  - The purpose of this study was to determine whether a methicillin-resistant strain
      of Staphylococcus aureus (MRSA) could be sensitised by toluidine blue O (TBO) to
      killing by light from a low-power helium/neon (HeNe) laser. Suspensions
      containing c. 10(10) cfu of MRSA were irradiated with light from a 35 mW HeNe
      laser (energy dose: 0.5-2.1 J) in the presence of TBO (1.6-12.5 micrograms/ml)
      and the survivors were enumerated. The kills attained depended on both the light
      energy dose and concentration of TBO employed. A 4.47 log10 reduction in the
      viable count was achieved with a TBO concentration of 12.5 micrograms/ml and a
      light dose of 2.1 J (energy density 43 J/cm2). MRSA were susceptible to killing
      by the laser light within 30 s of exposure to the TBO. The results of this study
      have demonstrated that MRSA can be rapidly sensitised by TBO to killing by HeNe
      laser light and that killing depends on the light energy dose and sensitiser
      concentration.

PMID- 7739028
TI  - Identification of pioneer viridans streptococci in the oral cavity of human
      neonates.
AB  - Three hundred and sixty-seven strains of pioneer streptococci isolated from the
      mouths of 40 healthy, full-term infants during the first month of life were
      examined by two taxonomic schemes that incorporated biochemical and physiological
      characteristics, IgA1 protease production and glycosidase activities.
      Streptococcus mitis biovar 1 and S. oralis comprised 55.0% of the pioneer
      streptococci isolated from neonates. S. salivarius constituted 25.3% of the
      isolates, while S. anginosus, S. mitis biovar 2, S. sanguis and S. gordonii
      accounted collectively for 11.4%. Difficulties in identifying streptococci were
      encountered and 8.4% of the 367 isolates could not be assigned to a recognised
      species.

PMID- 7739029
TI  - A nomothetic-idiographic study of daily psychological stress and blood glucose in
      women with type I diabetes mellitus.
AB  - Although there has been some study of the extralaboratory generality of stress
      effects on diabetic metabolism, analysis of the diabetic response to everyday
      life stress is needed. The secondary objective of this study was to investigate
      whether personal characteristics moderate the daily stress-glucose relationship.
      Twenty-five women with Type I diabetes completed measures of internality and self
      esteem and subsequently monitored daily stress and blood glucose for 30
      consecutive days. Data were analyzed by both time-series and conventional
      correlational analyses. Glucose was higher on high-stress days than on low-stress
      days, with one-third of the sample showing significant positive associations
      between stress and same-day glucose. However, stress showed little relation to
      next-day glucose. Personal characteristics failed to explain differences in
      stress-glucose associations. Implications for practice and future research are
      presented.

PMID- 7739030
TI  - Patient adherence and adjustment in renal dialysis: a person x treatment
      interactive approach.
AB  - We classified 52 in-center hemodialysis patients and 34 self-treated, continuous
      ambulatory peritoneal dialysis (CAPD) patients on two latent variable indices
      reflecting patient coping style (i.e., "Information Vigilance" and "Active
      Coping"). The concurrent and prospective interactive effects of Dialysis Type and
      Coping Style were examined on patient dietary and medication adherence and on
      patient depression. In cross-sectional analyses, higher Information Vigilance was
      associated with better dietary adherence for CAPD patients but poorer adherence
      for In-Center Hemodialysis patients. No significant effects were found on a
      measure of medication adherence. Information Vigilance exerted a concurrent main
      effect on depression, such that higher scores were associated with less
      depression irrespective of dialysis type. Higher Active Coping scores were
      associated with lower residualized change in depression for both types of
      dialysis.

PMID- 7739031
TI  - High-risk studies are influenced by indirect range restriction.
AB  - High-risk studies select subjects who are at high risk for existing or future
      disease. Therefore, the range of disease is restricted in high-risk studies. This
      paper shows that high-risk studies are vulnerable to a particular type of range
      restriction referred to as indirect range restriction. A simulation study is used
      to illustrate the effects of indirect range restriction on high-risk studies. The
      results suggest that indirect range restriction can have a substantial impact on
      the results of high-risk studies. In addition, a review of several areas of
      behavioral medicine research suggests that high-risk studies have produced many
      misleading findings. The range restriction approach can be used to estimate
      statistical power in high-risk studies, interpret the results of high-risk
      studies, and design future high-risk studies.

PMID- 7739033
TI  - Association of stress and depression with regional fat distribution in healthy
      middle-aged men.
AB  - We examined whether the association of regional fat distribution with stress,
      defined in terms of vital exhaustion, and depression varies according to the
      total amount of body fat accumulation in healthy middle-aged men (n = 64).
      Regional fat distribution was measured using the waist-to-hip circumference ratio
      (WHR), and the total amount of body fat accumulation was measured using the body
      mass index (BMI). The results indicate that WHR in lean men was associated with
      characteristics contrary to those in moderately obese men. In lean men WHR tended
      to be associated with a high level of stress, while in moderately obese men an
      association was found with a low level of stress and a low level of depressive
      symptomatology. The present results support the suggestion that there is a
      difference between abdominal obesity at different degrees of generalized obesity,
      and they are likely to further our understanding about the differing risk for
      cardiovascular disorders posed by abdominal obesity in lean men compared to
      abdominal obesity in moderately obese men.

PMID- 7739034
TI  - Specific protection of 16 S rRNA by translational initiation factors.
AB  - The binding of initiation factors to 30 S ribosomal subunits protects specific
      sets of nucleotides in 16 S rRNA from base-specific chemical probes. Initiation
      factor 3 (IF-3) protects residues G700, G703 and G791 from attack by kethoxal.
      These protected bases are close to those in 16 S rRNA that are protected by 50 S
      subunits, providing a structural basis for the subunit dissociation activity of
      IF-3. The IF-3-dependent protections also flank bases that are protected by P
      site-bound tRNA, in keeping with the possibility that IF-3 may interact with
      initiator tRNA, or influence the properties of the 30 S P site during initiation.
      IF-1 protects G530, A1492 and A1493 and causes enhanced reactivity of A1408.
      These bases are precisely the ones that are protected by the binding of tRNA to
      the ribosomal A site. This suggests that IF-1 mimics A-site-bound tRNA, and could
      serve to prevent premature binding of aminoacyl tRNA by blocking the 30 S A site.
      We were unable to detect any effect of IF-2 on the reactivity pattern of 16 S
      rRNA, suggesting that this factor may interact primarily through protein-protein
      interactions.

PMID- 7739032
TI  - Effects of dietary fat feedback on behavioral and psychological variables.
AB  - This paper reports on the immediate and delayed reactions to dietary fat
      consumption feedback. Subjects in our study received (1) personalized dietary fat
      feedback and (2) information about how to alter their fat consumption. Fat
      consumption was measured using a brief fat assessment instrument. Subjects were
      categorized into three risk groups: at or below, above, and significantly above
      the recommended level. Emotional, cognitive, and behavioral reactions were
      measured immediately after receiving feedback and at 1 month postfeedback.
      Subjects who received high fat feedback showed greater negative emotional
      distress in response to the feedback and stated that they knew less about high
      fat foods than subjects receiving lower feedback. By the 1-month follow-up,
      subjects in the highest feedback condition were least likely to report intentions
      to lower their dietary fat. Interventions designed to alter dietary fat
      consumption should take into account the emotional and cognitive consequences of
      risk factor feedback.

PMID- 7739035
TI  - A hotspot for promoter-dependent recombination in polyomavirus DNA.
AB  - We have engineered polyomavirus (Py) DNA molecules carrying two large direct
      repeats within the late coding region, as well as a deletion encompassing the
      TATA box in the early promoter. Such constructs recombine less readily than a
      construct containing the same duplication of late sequences, but an intact early
      promoter. Furthermore, residual recombination in the molecules with a deletion
      occurs between homologous sites which differ from those used in the molecule
      without deletion. These findings are consistent with recombination being
      stimulated by transcription originating from the early promoter, rather than
      facilitated by the "openness" of viral chromatin undergoing transcription.

PMID- 7739036
TI  - Multiple crystal forms of endoglucanase CelD: signal peptide residues modulate
      lattice formation.
AB  - The crystal structure of Clostridium thermocellum endoglucanase CelD revealed an
      extended NH2-terminal segment (involving residues from the putative leader
      peptide) sticking out from the enzyme core to interact with a symmetry related
      molecule through an intermolecular salt bridge (Lys38-Asp201). Enzymatic
      digestion of CelD with various proteases emphasized the flexibility of the NH2
      segment in solution. Proteolytic removal of Lys38 or the substitution of bridge
      forming residues by site-directed mutagenesis promoted crystal packing
      arrangements that differ from that of wild type CelD. Crystals of wild-type CelD
      (a = 99.3 A c = 191.8 A) are trigonal, space group P3(1)21, with one molecule in
      the asymmetric unit (form A), whereas crystals of papain-treated CelD (a = 100.4
      A, c = 248.7 A), of CelDK38M (a = 100.1 A, c = 248.4 A) and of papain-treated
      CelDD201A (a = 99.9 A, c = 250.0 A) are trigonal, space group P3(1)21, with two
      crystallographically independent molecules (form B), and crystals of chymotrypsin
      treated CelD (a = 100.0 A, c = 254.3 A) and of CelDD201A (a = 99.8 A, c = 254.7
      A) are hexagonal, space group P6(1)22, with one molecule in the asymmetric unit
      (form C). Only chymotrypsin-treated CelD (which preserves both Lys38 and Asp201)
      can grow in crystal form A upon macroseeding, indicating that formation of the
      intermolecular salt bridge is critical for stability of this crystal form.
      Flexible NH2- and COOH-terminal peptide extensions were found to influence
      crystal nucleation, but not crystal growth. The crystal structures of papain
      treated CelD and chymotrypsin-treated CelD, determined at 3.5 A resolution by
      molecular replacement techniques, demonstrate that a small change in molecular
      orientation promoted by Lys38 account for the differences between crystal forms B
      and C.

PMID- 7739037
TI  - A phase diagram for sodium and potassium ion control of polymorphism in telomeric
      DNA.
AB  - Switching between antiparallel and parallel quadruplex structures of telomeric
      DNA under the control of intracellular Na+ and K+ has been implicated in the
      pairing of chromosomes during meiosis. Using Raman spectroscopy, we have
      determined the dependence of the interquadruplex equilibrium of the telomeric
      repeat of Oxytricha nova, upon solution concentrations of Na+ and K+. Both alkali
      cations facilitate the formation of an antiparallel foldback quadruplex at low
      concentration, and a parallel extended quadruplex at higher concentration.
      However, K+ is more effective than Na+ in inducing the parallel association. We
      propose a phase diagram relating d(T4G4)4 polymorphism to intracellular
      [Na+]/[K+] ratios. The phase diagram indicates that the interquadruplex
      equilibrium is highly sensitive to changes in the mole fraction of either cation
      when the total concentration falls within the interval 65 to 225 mM, a range
      which encompasses total of the Na+ and K+ concentrations occurring in a typical
      mammalian cell. These results support a role for the guanine-rich overhang of
      eukaryotic DNA in promoting chromosome association during meiotic synapsis.

PMID- 7739038
TI  - DNA recognition site analysis of Xenopus winged helix proteins.
AB  - DNA binding proteins of the winged helix family contain a conserved 110 amino
      acid region, the fork head/HNF-3 domain. Three members of the recently described
      XFD (Xenopus fork head domain related) multigene family in the frog Xenopus
      laevis that contain this DNA-binding domain have been studied. We determined the
      in vitro DNA recognition sequences by means of two independent methods: PCR
      supported site selection with degenerated deoxyoligonucleotides and affinity
      chromatography of genomic Xenopus DNA fragments. In contrast to a remarkable
      sequence divergence within their protein sequence of the fork head domains, all
      three proteins share a similar 7 bp DNA target motif. The protein-DNA interaction
      has been studied by means of DMS interference and hydroxyl radical footprinting.
      A region of 18 bp encompassing the 7 bp target motif is sufficient to confer
      binding and specificity. The specificity of binding could be attributed on the
      DNA level to residues located 5' to the 7 bp core region, and on the protein
      level most likely to a region within the first half of the fork head domain. The
      possible role of specific nucleotides within the target site in binding the
      protein is discussed in the context of the current crystal structure of the
      complex of this domain with DNA.

PMID- 7739039
TI  - Functional interaction between the CSE2 gene product and centromeres in
      Saccharomyces cerevisiae.
AB  - The cse2-1 allele was identified through a genetic screen for mutations affecting
      chromosome segregation in Saccharomyces cerevisiae. This mutation confers cold
      and temperature sensitivity and causes increases in mitotic chromosome non
      disjunction and loss. The CSE2 gene encodes a 17 kDa protein with a basic region
      leucine zipper motif. Disruption of CSE2 is not lethal but results in the
      accumulation of large-budded cells. Here, we report that disruption of CSE2
      results in a significant increase in chromosome missegregation, slower growth and
      defective meiosis. The combination of the CSE2 disruption and a mutant centromere
      results in a synergistic effect on both cell growth and cell viability. These
      data suggest a functional interaction between the CSE2 protein and the yeast
      centromere.

PMID- 7739040
TI  - Structural plasticity of the nuclear pore complex.
AB  - The nuclear pore complex (NPC) is strategically located at continuous junctions
      of the inner and outer nuclear membranes to catalyze macromolecular transport,
      without impending the diffusion of small molecules. In this paper, the structural
      plasticity of 4412 NPCs in isolated nuclear envelopes has been evaluated,
      utilizing correspondence analysis, classification and difference mapping. The
      data are grouped into seven clusters comprising two major groups, based on the
      degree of radial compaction within spokes and the symmetry of the inner spoke
      ring. The results have been correlated with differences in spoke domain packing
      observed in two published three-dimensional maps suggesting that symmetrical
      detergent-extracted NPCs are similar, but not identical to the most probable in
      vivo structure. A model is proposed in which spoke architecture is responsive to
      changes in the turgor pressure of the nuclear envelope. For example, detergent
      extraction may allow the outward facing domains of each spoke to adopt a radially
      extended configuration while osmotic swelling may induce an inwards displacement,
      resulting in a radially compact spoke. Difference maps between approximately 822
      symmetric projections of NPCs in membranes and after detergent-extraction have
      localized the nuclear envelope border. The data place limits on the radial and
      circumferential dimensions of diffusion channels (approximately 0 to 20 A x 190
      A), proposed to reside at the pore periphery. The results confirm the observation
      that each spoke penetrates the nuclear envelope, linking up with the radial arms
      to form a "lumenal ring". Finally, putative closed, open and in-transit forms of
      the transporter are found with the same relative frequency in membrane-associated
      NPCs with radially compact or extended spokes; hence spoke deformations in
      isolated envelopes may be induced by experimental factors. However, concerted
      movements of the spoke domains (if reversible) may be utilized in the biological
      function of the NPC and some examples are given.

PMID- 7739041
TI  - Rigor cross-bridges bind to two actin monomers in thin filaments of rabbit psoas
      muscle.
AB  - The mode of binding of myosin subfragment-1 (S1) to actin is known to depend on
      their molar ratio: when actin is in excess, S1 binds to two actin monomers within
      the actin filament, and when S1 is in excess or is equimolar with actin, each S1
      binds to one actin monomer. Since in vertebrate striated muscle actin is in molar
      excess over myosin, we expect that in fibers each myosin head binds to two actin
      monomers. To test this idea, we compared the conformation of the heads in native
      muscle with the conformation of S1 in fibers that were loaded with either high
      (S1 equimolar with actin) or low (excess of actin over S1) concentration of
      extrinsic S1. Conformation was assessed by the accessibility of heads to trypsin
      (measured by the rate of trypsinolysis) and by their orientation with respect to
      the muscle axis (measured by a combination of polarization of fluorescence and
      linear dichroism). In muscle fibers loaded with a high concentration of S1, the
      region of the heavy chain of the myosin head at the junction of 20 and 50 kDa
      proteolytic fragments was readily digested by trypsin and its orientation was
      approximately perpendicular to an axis of a thin filament. In contrast, when
      muscle fibers were loaded with a low concentration of S1, the 20/50 kDa junction
      of S1 was protected from trypsinolysis and its orientation was more parallel with
      a filament axis. Native muscle in rigor behaved like muscle irrigated with a low
      concentration of S1, i.e. the 20/50 kDa junction of the myosin head was protected
      from trypsinolysis and the orientation of the heads was parallel to the filament
      axis. We conclude that in rigor rabbit psoas muscle each myosin head binds to two
      actin monomers in a thin filament, and that this binding is different from the
      binding of S1 to actin in equimolar solutions.

PMID- 7739042
TI  - The complete primary structure of human nebulin and its correlation to muscle
      structure.
AB  - Nebulin is a giant filamentous protein specific for vertebrate skeletal muscles.
      The correlation of its size to thin filament lengths in vertebrates suggests that
      nebulin may function as a molecular ruler to determine thin filament length. We
      have isolated a full-length cDNA of 20.8 kb encoding human nebulin and determined
      its sequence. The cDNA's predicted peptide has a molecular weight of 773 kDa, and
      97% of its mass consists of 185 copies of -35-residue module. Within the
      molecule, different sub-families of modules can be distinguished, and their
      arrangement is correlated to the structure of the thin filament. The central 154
      copies are grouped into 22 seven-module super repeats corresponding to 38.5 nm
      thin filament repeats. In the thin filament ruler region, multiple isoforms are
      generated by alternative exon usage which is likely to explain the developmental
      and tissue-specific size variations of nebulins previously found in vertebrate
      skeletal muscles. We propose that different types of nebulin molecular rulers are
      expressed in the different types of skeletal muscles by differential splicing.
      Outside the super repeat region, the presence of distinct module arrangements
      implies functional diversity of the nebulin module family. A novel "simple
      repeat" family together with an SH3 domain at the C-terminus appear to anchor the
      nebulin filament system in the Z-disc. Nebulin's SH3 domain is highly related in
      sequence to the SH3 domains in yeast actin binding protein ABP-1 and to the src
      substrate p80/85 in chicken, both proteins which are involved in regulating actin
      assembly of the cytoskeleton in non-muscle cells. Study of nebulins terminal
      sequences is likely to reveal how integration of the nebulin filament into the
      sarcomere is regulated.

PMID- 7739044
TI  - Three-dimensional structure of a lipoyl domain from the dihydrolipoyl
      acetyltransferase component of the pyruvate dehydrogenase multienzyme complex of
      Escherichia coli.
AB  - The structure of a lipoyl domain from the pyruvate dehydrogenase multienzyme
      complex of Escherichia coli has been determined by means of nuclear magnetic
      resonance spectroscopy. A total of 549 nuclear Overhauser effect distance
      restraints, 52 phi torsion angle restraints and 16 slowly exchanging amide
      protons were employed as input for the structure calculations. These were
      performed using a combined distance geometry-simulated annealing strategy. The
      domain is a hybrid between the N and C-terminal halves of the first and third
      lipoyl domains, respectively, of the dihydrolipoyl acetyltransferase component of
      the E. coli multienzyme complex, representing residues 1 to 33 and 238 to 289
      (wild-type numbering). The lipoyl-lysine residue was also replaced by glutamine.
      Nonetheless, its structure, two four-stranded beta-sheets forming a flattened
      beta-barrel, closely resembles that of the lipoyl domain from the pyruvate
      dehydrogenase multienzyme complex from Bacillus stearothermophilus determined
      previously. As before, the lipoylation site is physically exposed in a tight turn
      in one of the beta-sheets, and the N and C-terminal residues are close together
      at the other end of the molecule in adjacent strands of the other beta-sheet.
      Another prominently conserved feature of the structure is the 2-fold axis of
      quasi-symmetry relating the N and C-terminal halves of the domain. Consistent
      with the high level of sequence similarity between lipoyl domains of 2-oxo acid
      dehydrogenase multienzyme complexes from many different sources, these results
      confirm that all lipoyl domains are likely to have closely related structures.

PMID- 7739043
TI  - Molecular analysis of an A-protein secretion mutant of Aeromonas salmonicida
      reveals a surface layer-specific protein secretion pathway.
AB  - The Aeromonas salmonicida Tn5 mutant, A449-TM1, is unable to secrete the surface
      layer protein (A-protein) through the outer membrane. Immunogold labeling of thin
      sections of A449-TM1, with polyclonal antisera against the A-protein, showed the
      accumulation of large quantities of A-protein in an enlarged periplasm. The
      majority of the labeled A-protein could be seen at the poles of the cells. The
      ability of A449-TM1 to secrete other extracellular proteins such as hemolysin and
      protease was not impaired by the Tn5 insertion, which indicates that the mutation
      in A449-TM1 interferes with a secretion pathway specifically for the
      translocation of the A-protein through the outer membrane. The mutant, A449-TM1,
      was shown to be avirulent for fish. A cosmid clone from a gene library of A449
      TM1, which contains the Tn5 insertion from the chromosome, was used to identify a
      1.4 kb SaII/ClaI fragment from immediately adjacent to the Tn5 insertion. This
      fragment was used to identify and clone a 4 kb HindIII fragment from a
      chromosomal DNA digest from the wild-type strain, A449. DNA sequence analysis of
      this clone identified an open reading frame (ORF) of 1656 bp. The deduced product
      of this ORF showed sequence similarity to a family of ATP-binding secretion
      proteins, but appeared to be phylogenetically distinct from these proteins,
      consistent with its participation in a secretory pathway specific for surface
      layer protein.

PMID- 7739045
TI  - Structure and specificity of the anti-digoxin antibody 40-50.
AB  - We determined the sequence, specificity for structurally related cardenolides,
      and three-dimensional structure of the anti-digoxin antibody 40-50 Fab in complex
      with ouabain. The 40-50 antibody does not share close sequence homology with
      other high-affinity anti-digoxin antibodies. Measurement of the binding constants
      of structurally distinct digoxin analogs indicated a well-defined specificity
      pattern also distinct from other anti-digoxin antibodies. The 40-50-ouabain Fab
      complex crystallizes in space group C2 with cell dimensions of a = 93.7 A, b =
      84.8 A, c = 70.1 A, beta = 128.0 degrees. The structure of the complex was
      determined by X-ray crystallography and refined at a resolution of 2.7 A. The
      hapten is bound in a pocket extending as a groove from the center of the
      combining site across the light chain variable domain, with five of the six
      complementarity-determining regions involved in interactions with the hapten.
      Approximately three-quarters of the hapten surface area is buried in the complex;
      two hydrogen bonds are formed between the antibody and hapten. The surface area
      of the antibody combining site buried by ouabain is contributed equally by the
      light and heavy chain variable domains. Over half of the surface area buried on
      the Fab consists of the aromatic side-chains. The surface complementarity between
      hapten and antibody is sufficient to make the complex specific for only one
      lactone ring conformation in the hapten. The crystal structure of the 40-50
      ouabain complex allows qualitative explanation of the observed fine specificities
      of 40-50, including that for the binding of haptens substituted at the 16 and 12
      positions. Comparison of the crystal structures of 40-50 complexed with ouabain
      and the previously determined 26-10 anti-digoxin Fab complexed with digoxin,
      demonstrates that the antibodies bind these structurally related haptens in
      different orientations, consistent with their different fine specificities. These
      results demonstrate that the immune system can generate antibodies that provide
      diverse structural solutions to the binding of even small molecules.

PMID- 7739046
TI  - Coulombic interactions between partially charged main-chain atoms not hydrogen
      bonded to each other influence the conformations of alpha-helices and
      antiparallel beta-sheet. A new method for analysing the forces between hydrogen
      bonding groups in proteins includes all the Coulombic interactions.
AB  - An angle named gamma has been employed to describe the geometry at a hydrogen
      bond between main-chain atoms of polypeptides. In antiparallel beta-sheet, gamma
      is normally positive, whereas, in parallel beta-sheet and alpha-helices, it is
      negative. Although intriguing, no particular explanation has been offered to
      explain this result. We provide evidence that, in each case, the angular
      preference maximises the favourable Coulombic interaction between the partial
      negative charge on the carbonyl oxygen atom and the partial positive charge on
      the carbonyl carbon atom adjacent to the NH group to which it is hydrogen-bonded.
      Analyses of helices and beta-sheets in native proteins using Lennard-Jones
      potentials suggest that these carbonyl-carbonyl interactions are significant
      components of the attractive forces holding main-chain CONH groups together and
      are even in some cases larger than the hydrogen bonds themselves. A novel
      technique for analysing the forces holding together hydrogen-bonding groups in
      proteins is presented. It can be regarded as a development of the Kabsch and
      Sander method of calculating the energy of hydrogen bonds between main-chain
      atoms. In their program, electrostatic interactions are calculated between
      appropriate pairs of atoms, i.e. NH binding to CO. Instead, in our method, the
      four N, H, C, and O atoms, in a peptide bond are taken as a unit and the
      interaction between two NHCO groups calculated. We also use a Lennard-Jones
      potential, rather than just measuring the Coulombic interaction. With this
      approach, account is taken of all types of interactions between partially charged
      atoms, not only the hydrogen bonds.

PMID- 7739047
TI  - Coulombic attractions between partially charged main-chain atoms stabilise the
      right-handed twist found in most beta-strands.
AB  - The use of Lennard-Jones potentials gives rise to an expected energy distribution
      for main-chain polypeptide conformations in the Ramachandran plot that matches
      well the observed distribution of phi, psi values in high-resolution proteins.
      The position of the energy minimum in the beta-strand conformation region is
      situated where there is a substantial contribution from the electrostatic
      attraction between the partial charge of the carbonyl carbon atom of one amino
      acid residue and that of the carbonyl oxygen atom of an adjacent residue. This
      attraction gives rise to a preference for the right-twisted beta-strand
      conformation compared with the left-twisted conformation. The majority of beta
      sheets are twisted, almost always in one direction. Looking along a single
      strand, the twist is to the right. This twist also helps provide a rationale for
      the characteristic topology of the strand-helix-strand unit often observed in
      alpha/beta proteins. The electrostatic explanation for the twist we propose has
      not, to our knowledge, been explicitly suggested previously. The factor that has
      been most widely proposed to explain the twist is steric hindrance involving side
      chain atoms. We provide evidence that the electrostatic effect is of comparable
      significance. Right-twisted beta-strands are geometrically closely related to
      polyproline II helices and to collagen helices, both of which are left-handed.
      Short regions of polyproline II type helices, which are sometimes, but not
      always, rich in proline residues, are common at protein surfaces. We point out
      that these helices are stabilised by the same carbonyl-carbonyl interactions as
      in right-twisted beta-strands.

PMID- 7739048
TI  - Solution structure of human insulin-like growth factor II. Relationship to
      receptor and binding protein interactions.
AB  - The three-dimensional structure of human insulin-like growth factor (IGF) II in
      aqueous solution at pH 3.1 and 300 K has been determined from nuclear magnetic
      resonance data and restrained molecular dynamics calculations. Structural
      constraints consisting of 502 NOE-derived distance constraints, 11 dihedral angle
      restraints, and three disulfide bridges were used as input for distance geometry
      calculations in DIANA and X-PLOR, followed by simulated annealing refinement and
      energy minimization in X-PLOR. The resulting family of 20 structures was well
      defined in the regions of residues 5 to 28 and 41 to 62, with an average pairwise
      root-mean-square deviation of 1.24 A for the backbone heavy-atoms (N, C2, C) and
      1.90 A for all heavy atoms. The poorly defined regions consist of the N and C
      termini, part of the B-domain, and the C-domain loop. Resonances from these
      regions of the protein gave stronger cross peaks in two dimensional NMR spectra,
      consistent with significant motional averaging. The main secondary structure
      elements in IGF-II are alpha-helices encompassing residues 11 to 21, 42 to 49 and
      53 to 59. A small anti-parallel beta-sheet is formed by residues 59 to 61 and 25
      to 27, while residues 26 to 28 appear to participate in intermolecular beta-sheet
      formation. The structure of IGF-II in the well-defined regions is very similar to
      those of the corresponding regions of insulin and IGF-I. Significant differences
      between IGF-II and IGF-I occur near the start of the third helix, in a region
      known to modulate affinity for the type 2 IGF receptor, and at the C terminus.
      The IGF II structure is discussed in relation to its binding sites for the
      insulin and IGF receptors and the IGF binding proteins.

PMID- 7739049
TI  - The refined crystal structure of an endochitinase from Hordeum vulgare L. seeds
      at 1.8 A resolution.
AB  - Class II chitinases (EC 3.2.1.14) are plant defense proteins. They hydrolyze
      chitin, an insoluble beta-1,4-linked polymer of N-acetylglucosamine (NAG), which
      is a major cell-wall component of many fungal hyphae. We previously reported the
      three-dimensional structure of the 26 kDa class II endochitinase from barley
      seeds at 2.8 A resolution, determined using multiple isomorphous replacement
      (MIR) methods. Here, we report the crystallographic refinement of this chitinase
      structure against data to 1.8 A resolution using rounds of hand rebuilding
      coupled with molecular dynamics (X-PLOR). The final model has an R-value of 18.1%
      for the 5.0 to 1.8 A data shell and 19.8% for the 10.0 to 1.8 A shell, and root
      mean-square deviations from standard bond lengths and angles of 0.017 A and 2.88
      degrees, respectively. The 243 residue molecule has one beta-sheet, ten alpha
      helices and three disulfide bonds; 129 water molecules are included in the final
      model. We show structural comparisons confirming that chitinase secondary
      structure resembles lysozyme at the active site region. Based on substrate
      binding to lysozyme, we have built a hypothetical model for the binding of a
      hexasaccharide into the pronounced active site cleft of chitinase. This provides
      the first view of likely substrate interactions from this family of enzymes; the
      model is consistent with a lysozyme-like mechanism of action in which Glu67 acts
      as proton donor and Glu89 is likely to stabilize the transition state
      oxycarbonium ion. These binding site residues, and many hydrophobic residues are
      conserved in a range of plant chitinases. This endochitinase structure will serve
      as a model for other plant chitinases, and that catalytic models based on this
      structure will be applicable to the entire enzyme family.

PMID- 7739050
TI  - Domain structure, stability and domain-domain interactions in recombinant factor
      XIII.
AB  - The process of heat denaturation of recombinant factor XIII (rFXIII), as well as
      its C-terminal 24 kDA and 12 kDa elastase-produced fragments starting at Ser514
      and Thr628, respectively, was investigated in a wide range of conditions by
      fluorescence, CD and differential scanning calorimetry (DSC). It was found that
      the intact protein melts in two distinct temperature regions reflecting unfolding
      of different parts of the molecule with different stability. The less stable
      structures unfold in a low temperature transition with a tm of 69 degrees C or
      lower depending on conditions. Unfolding of the more stable structures was
      observed at extremely high temperatures, tm > 110 degrees C at acidic pH < 3.5
      and tm = 90 degrees C at pH 8.6 with 2 M GdmCL. Thermodynamic analysis of the low
      and high temperature DSC-obtained heat absorption peaks indicated unambiguously
      that the first represents melting of three thermolabile independently folded
      domains while two thermostable domains melt in the second one giving a total of
      five domains in each a subunit of rFXIII. Both 24 kDa and 12 kDa fragments
      exhibited a sigmoidal spectral transition at comparatively high temperature where
      the thermolabile structures are already denatured, indicating that two
      thermostable domains are formed by the C-terminal portion of rFXIII and
      correspond to the two beta-barrels revealed by crystallography. The remaining 56
      kDa portion forms three thermolabile domains, one of which corresponds to the N
      terminal beta-sandwich and the other two to the catalytic core. Fast accessible
      surface calculations of the X-ray model of rFXIII confirmed the presence of two
      structural subdomains in the core region with the boundary at residue 332. The
      thermolabile domains appear to interact with each other intra- and/or
      intermolecularly resulting in dimerization the a subunits. At acidic pH, where
      all domains became destabilized but still remained folded, interdomainial
      interactions seemed to be abolished, resulting in the reversible dissociation of
      the dimer as revealed by ultracentrifugation analysis.

PMID- 7739051
TI  - Three-dimensional reconstruction of the alpha D and beta C-hemocyanins of Helix
      pomatia from frozen-hydrated specimens.
AB  - The three-dimensional (3D) reconstructions of the di-decameric forms of alpha D
      and beta C-hemocyanins of the Roman snail Helix pomatia and of the decameric half
      molecules of alpha D-hemocyanin were carried out on frozen-hydrated specimens
      observed in the electron microscope by using the random conical tilt series
      method. The three 3D volumes were examined by computing solid-body surface
      representations and slices through the volume and by eroding the structure
      progressively through raising of the threshold. The di-decameric molecule of
      alpha D and beta C-hemocyanins, reconstructed from side views, are very similar
      and are composed of a cylindrical wall, comprising ten oblique wall units, and of
      two collar complexes located at both ends of the cylinder, comprising each five
      arches and an annular collar made up of five collar units. Erosion of the
      structure reveals that the wall looks like a segment of a five-stranded right
      handed helix and that each oblique wall unit resembles a figure 8 inclined to the
      right. The decameric half molecule of alpha D-hemocyanin, reconstructed from end
      on views, resembles the whole molecule, except that the collar is thinner and
      appears composed of five independent collar complex units. It is suggested that
      the difference in structural appearance of the collar complex between the whole
      and the half alpha D-hemocyanin may be due to the missing cone artifact, induced
      by the angular limitations imposed by the goniometer of the electron microscope.
      The comparison between the alpha D-hemocyanin and the beta C-di-decameric
      hemocyanin at high thresholds suggests that in the beta C-hemocyanin the oblique
      wall units of each half molecule may be linked by two connections, whereas in
      alpha D-hemocyanin there may be only one. This difference in the number of
      connections may be responsible for the lower stability of the alpha D molecule at
      high salt concentration.

PMID- 7739052
TI  - Solution structure of an Old World-like neurotoxin from the venom of the New
      World scorpion Centruroides sculpturatus Ewing.
AB  - We have determined the solution structure of an alpha-toxin, CsE-V, isolated from
      the venom of the New World scorpion Centruroides sculpturatus Ewing (CsE). This
      toxin causes spontaneous rhythmic contractions in muscle. Unlike other New World
      toxins from CsE, this protein exhibits amino acid insertions and deletions at
      locations similar to Old World toxins and may thus represent a transition protein
      between the New World and Old World scorpion alpha-toxins. Sequence-specific
      assignments were made using 600 MHz 1H two-dimensional NMR data. NOESY, PH-COSY
      and amide-exchange data were used to deduce constraints for molecular modeling
      calculations. Distance geometry and dynamical simulated annealing calculations
      were performed to generate a family of 70 structures free of constraint
      violations. With respect to this family of structures, the energy-minimized
      average structure had root-mean-square deviations of 0.74 and 1.32 A for backbone
      and all atoms, respectively (excluding the C-terminal dipeptide, which is
      disordered). As with other scorpion toxins, the secondary structure of CsE-V
      consists of an alpha-helix, a three-strand anti-parallel beta-sheet, four beta
      turns, and a hydrophobic patch that includes tyrosine residues in herringbone
      configuration. Unlike the CsE-v3 and -v1 proteins from C. sculpturatus, all of
      the proline residues were found to be in the trans configuration. The alpha-helix
      is slightly longer in CsE-V. The overall structure is more similar to the Old
      World alpha-toxin AaH-II from Androctonus australis Hector (r.m.s.d 1.59 A for
      backbone atoms of matching residues) than to the New World alpha-toxin CsE-v3
      (r.m.s.d. 1.91 A). These structural data on CsE-V add further to our knowledge of
      the conformational repertoire exhibited by these sodium channel-binding
      neurotoxins.

PMID- 7739053
TI  - A geometry-based suite of molecular docking processes.
AB  - We have developed a geometry-based suite of processes for molecular docking. The
      suite consists of a molecular surface representation, a docking algorithm, and a
      surface inter-penetration and contact filter. The surface representation is
      composed of a sparse set of critical points (with their associated normals)
      positioned at the face centers of the molecular surface, providing a concise yet
      representative set. The docking algorithm is based on the Geometric Hashing
      technique, which indexes the critical points with their normals in a
      transformation invariant fashion preserving the multi-element geometric
      constraints. The inter-penetration and surface contact filter features a three
      layer scoring system, through which docked models with high contact area and low
      clashes are funneled. This suite of processes enables a pipelined operation of
      molecular docking with high efficacy. Accurate and fast docking has been achieved
      with a rich collection of complexes and unbound molecules, including protein
      protein and protein-small molecule associations. An energy evaluation routine
      assesses the intermolecular interactions of the funneled models obtained from the
      docking of the bound molecules by pairwise van der Waals and Coulombic
      potentials. Applications of this routine demonstrate the goodness of the high
      scoring, geometrically docked conformations of the bound crystal complexes.

PMID- 7739055
TI  - Clinic explores novel approaches to improving health in Hispanic community.

PMID- 7739054
TI  - Energetics of protein-protein interactions: analysis of the barnase-barstar
      interface by single mutations and double mutant cycles.
AB  - The interaction of barnase, an extracellular RNase of Bacillus amylolique
      faciens, with its intracellular inhibitor barstar is a suitable paradigm for
      protein-protein interactions, since the structures of both the free and the
      complexed proteins are available at high resolution. The contributions of
      residues from both proteins to the energetics of kinetics and thermodynamics of
      binding were measured by double mutant cycle analysis. Such cycles reveal whether
      the contributions from a pair of residues are additive, or the effects of
      mutations are coupled. The aim of the study was to determine which of the
      interactions are co-operative. Double mutant cycles were constructed between a
      subset of five barnase and seven barstar residues, which were shown by structural
      and mutagenesis studies to be important in stabilising the complex. The coupling
      energy between two residues was found to decrease with the distance between them.
      Generally, residues separated by less than 7 A interact co-operatively. At
      greater separations, the effects of mutation are additive, and the energetics of
      the interactions are independent of each other. The highest coupling energies are
      found between pairs of charged residues (1.6 to 7 kcal mol-1). Three of the six
      most important interactions detected by double mutant cycle analysis (with
      coupling energies of more than 3.0 kcal mol-1) had not been noted previously from
      examination of the crystal structure. The effects of mutation on the kinetics of
      association are all additive, apart from charged residues located at distances of
      up to 10 A apart, which are co-operative. This can be explained by the fact that
      the transition state for association occurs before most interactions are formed.

PMID- 7739056
TI  - Along US southern border, pollution, poverty, ignorance, and greed threaten
      nation's health.

PMID- 7739057
TI  - From the Health Care Financing Administration.

PMID- 7739058
TI  - From the Centers for Disease Control and Prevention. Children at risk from ozone
      air pollution--United States, 1991-1993.

PMID- 7739059
TI  - From the Center for Disease Control and Prevention. Prevention program for
      reducing risk for neural tube defects--South Carolina, 1992-1994.

PMID- 7739060
TI  - Private sector volunteerism as a solution to caring for the uninsured.

PMID- 7739061
TI  - Private sector volunteerism as a solution to caring for the uninsured.

PMID- 7739062
TI  - Private sector volunteerism as a solution to caring for the uninsured.

PMID- 7739063
TI  - The relationship between physicians' malpractice claims history and later claims.

PMID- 7739064
TI  - The relationship between physicians' malpractice claims history and later claims.

PMID- 7739065
TI  - The relationship between physicians' malpractice claims history and later claims.

PMID- 7739066
TI  - Fluoxetine and sexual dysfunction.

PMID- 7739067
TI  - Fluoxetine and sexual dysfunction.

PMID- 7739068
TI  - Fluoxetine and sexual dysfunction.

PMID- 7739069
TI  - Pharmacologic treatment of congestive heart failure.

PMID- 7739070
TI  - Pharmacologic treatment of congestive heart failure.

PMID- 7739071
TI  - Pharmacologic treatment of congestive heart failure.

PMID- 7739072
TI  - Retinal tear after teeth cleaning.

PMID- 7739074
TI  - A piece of my mind. Sudden death.

PMID- 7739073
TI  - Effects of Agent Orange exposure.

PMID- 7739075
TI  - The influence of market economics on primary health care in Vietnam.

PMID- 7739076
TI  - Variation in office-based quality. A claims-based profile of care provided to
      Medicare patients with diabetes.
AB  - OBJECTIVES: To demonstrate that claims data "profiling" can be used as an ongoing
      method to support ambulatory care quality improvement; to measure the quality of
      office-based care provided to elderly patients with diabetes in three states; and
      to identify factors associated with better attainment of quality standards. STUDY
      DESIGN: A cross-sectional study based on a 100% sample of the Medicare claims
      (Part B and Part A) submitted between July 1, 1990, and June 30, 1991. SETTING:
      All primary care practices (both solo and group) actively seeing Medicare
      patients with diabetes in Alabama, Iowa, and Maryland (n = 2980). PATIENTS: All
      elderly (> or = 65 years) Medicare patients seen by the study physicians and
      assigned a diagnosis of diabetes (n = 97,388) by any office-based physician
      during the year. MAIN OUTCOME MEASURES: The proportion of patients with diabetes
      receiving the following procedures (from any provider) at least once during the
      study period: hemoglobin A1C measurement, ophthalmologic examination, total
      cholesterol measurement, and blood glucose measurement. We considered the first
      three services to be optimally recommended and blood glucose measurement to be of
      limited use. RESULTS: Based on analyses of services provided in the ambulatory
      setting, we found that 84% of diabetics did not appear to receive the recommended
      hemoglobin A1C measurement, 54% did not see an ophthalmologist, and 45% received
      no cholesterol screening. Practice patterns varied considerably across the three
      states (up to 2.38-fold), even after adjusting for patient case mix and physician
      characteristics. Patients of general practitioners were less likely to meet
      recommended quality criteria than patients of internists or family practitioners.
      Patients receiving care from rural practitioners were less likely to receive
      services, either recommended or not, than those in urban locations. CONCLUSIONS:
      Elderly patients with diabetes do not appear to be receiving optimal care. This
      study underscores the value of practice guideline development and dissemination
      in the ambulatory arena. This study provides substantial evidence that existing
      administrative claims data can be used to support ambulatory quality improvement
      activities.

PMID- 7739077
TI  - Quality of care for Medicare patients with acute myocardial infarction. A four
      state pilot study from the Cooperative Cardiovascular Project.
AB  - OBJECTIVE: To develop and test indicators of the quality of care for patients
      with acute myocardial infarction (AMI). DESIGN: Retrospective medical record
      review. SETTING: All acute care hospitals in Alabama, Connecticut, Iowa, and
      Wisconsin. PATIENTS: All hospitalizations for Medicare patients discharged with a
      principal diagnosis of AMI between June 1, 1992, and February 28, 1993, were
      identified (N = 16,869). MAIN OUTCOME MEASURE: Percentage of patients receiving
      appropriate interventions as defined by 11 quality-of-care indicators derived
      from clinical practice guidelines that were modified and updated in consultation
      with a national group of physicians and other health care professionals. RESULTS:
      We abstracted data from 16,124 (96%) of the hospitalizations, representing 14,108
      primary hospitalizations and 2016 hospitalizations resulting from transfers.
      Potential exclusions to the use of standard treatments in AMI care were common
      with 90% and 70% of patients having potential exclusions for thrombolytics and
      beta-blockers, respectively. In cohorts of "ideal candidates" for specific
      interventions, 83% received aspirin, 69% received thrombolytics, and 70% received
      heparin during the initial hospitalization; 77% received aspirin and 45% received
      beta-blockers at discharge. CONCLUSIONS: These data demonstrate that many
      Medicare patients may not be ideal candidates for standard AMI therapies, but
      these treatments are underused, even in the absence of discernible
      contraindications. Hospitals and physicians who apply these quality indicators to
      their practices are likely to find opportunities for improvement.

PMID- 7739078
TI  - Physician race and care of minority and medically indigent patients.
AB  - OBJECTIVE: To examine the relationship between physician race and care of racial
      minority and ethnic minority patients and medically indigent patients. DESIGN:
      Secondary analysis of data from the 1987 National Medical Expenditure Survey, a
      cross-sectional survey of Americans designed to provide national estimates of
      health care utilization and expenditures. SETTING: A sample representative of the
      total civilian noninstitutionalized US population with oversampling of minorities
      and the medically indigent. PATIENTS: Survey respondents aged 18 years or older
      who identified a specific physician as their usual source of care (n = 15,081,
      corresponding to a national population estimate of 116 million Americans). MAIN
      OUTCOME MEASURE: Identification of a nonwhite physician as usual source of care.
      RESULTS: Of adult Americans who identified a usual-source-of-care physician,
      14.4% identified a nonwhite physician as that source of care. Minority patients
      were more than four times more likely to receive care from nonwhite physicians
      than were non-Hispanic white patients. Low-income, Medicaid, and uninsured
      patients were also more likely to receive care from nonwhite physicians.
      Individuals who receive care from nonwhite physicians were more likely to report
      worse health, visit an emergency department, and be hospitalized. Individuals who
      receive care from nonwhite physicians reported more acute complaints, chronic
      conditions, functional limitations, and psychological symptoms as well as longer
      visits. CONCLUSIONS: Nonwhite physicians are more likely to care for minority,
      medically indigent, and sicker patients. Caring for less affluent and sicker
      patients may financially penalize nonwhite physicians and make them particularly
      vulnerable to capitation arrangements.

PMID- 7739079
TI  - Medical migration and the physician workforce. International medical graduates
      and American medicine.
AB  - OBJECTIVE: Because of the size and growth of the international medical graduate
      (IMG) contribution to graduate medical education (GME) in the United States, and
      subsequently to the US physician workforce, it is essential to understand the
      demographics and patterns of IMG training and practice as well as the routes of
      entry into the United States. DATA SOURCES: Published data from the American
      Medical Association, the American Osteopathic Association, and the Association of
      American Medical Colleges; tabular runs of county-level data contained on the
      Bureau of Health Professions' Area Resource File. RESULTS: The majority of IMGs
      who participate in GME in the United States ultimately enter US practices. A
      significant proportion of exchange visitors eventually enter into permanent
      practice in the United States, contrary to the intent of the J-1 visa-based GME
      training as an international educational exchange program. International medical
      graduates gravitate toward initial residency programs in internal medicine and
      pediatrics, many of which have unfilled positions; however, IMGs subspecialize at
      a disproportionately high rate, reducing their net contribution to the generalist
      pool. Patterns of ultimate practice location of IMGs parallel the patterns of US
      medical graduates (USMGs). CONCLUSIONS: In recent years, participation of IMGs in
      GME and practice has increased significantly. Most IMGs in GME are not exchange
      visitors, but are either permanent residents or US citizens. Patterns of
      specialization and location of IMGs ultimately mirror those of USMGs. National
      IMG policy must be examined in light of the projected surplus of physicians in
      the United States. The best option for long-term control of the number of
      physicians in practice, USMG or IMG, is a system of specifying the number of GME
      positions nationally.

PMID- 7739080
TI  - Medicare funding of nurse education. The case for policy change.
AB  - OBJECTIVES: To determine the magnitude and distribution of US Medicare funding
      for nursing education and to assess the extent to which Medicare funding
      contributes to meeting national health care workforce priorities. DATA SOURCES:
      Medicare Hospital Cost Report Information System, American Hospital Association
      Annual Survey of Hospitals, and National League for Nursing national surveys of
      schools of nursing. DATA ANALYSIS: Using hospital identifiers, data from three
      data sets were merged and analyzed to estimate percentage distributions of
      Medicare funding according to types of educational programs, hospital
      characteristics, and student enrollment. RESULTS: Fifteen percent of direct
      Medicare graduate medical education funding goes to hospitals for the training of
      nurses and paramedical personnel. Totaling approximately $174 million in 1991,
      71% of these funds went to hospitals for nursing education costs. Most of the
      nation's teaching hospitals (289 of 381 Council of Teaching Hospitals member
      hospitals) and nurse education programs (1112 of 1484) do not qualify under
      existing policies for Medicare nursing education reimbursement. Sixty-six percent
      of Medicare nurse training funds, totaling $114 million in 1991, went to 145
      hospitals operating diploma nursing programs; these programs produce less than
      10% of nurse graduates. Three states (Pennsylvania, New Jersey, and Ohio)
      received nearly one half (48%) of the $114 million for diploma nursing education.
      CONCLUSIONS: Medicare is the largest single source of federal support for nursing
      education. Yet, the majority of Medicare nursing education funding goes to
      hospitals affiliated with an increasingly smaller, idiosyncratic subset of nurse
      training programs. Unlike graduate medical education, Medicare supports primarily
      preprofessional education in nursing. Graduate education, including the
      preparation of nurse practitioners, does not generally qualify for reimbursement.
      Medicare reimbursement for nursing education must be retargeted.

PMID- 7739081
TI  - Physician, educate thyself.

PMID- 7739083
TI  - Quality of measurement or quality of medicine?

PMID- 7739082
TI  - Translating medical science into medical practice. Do we need a national medical
      standards board?

PMID- 7739084
TI  - The failure of organized health system reform--now what? Caveat aeger--let the
      patient beware.

PMID- 7739085
TI  - The academic health care system. Preserving the missions as the paradigm shifts.

PMID- 7739087
TI  - [Postoperative pain management].

PMID- 7739086
TI  - Patient-physician covenant.

PMID- 7739088
TI  - [Inhibition of pulmonary vasoconstriction by inhaled nitric oxide].
AB  - We examined effects of inhaled NO gas on pulmonary vasoconstriction induced with
      hypoxic gas or PGF2 alpha utilizing the isolated perfused rabbit lung. While NO
      180 ppm did not change the basal pulmonary artery pressure, the pressure response
      to hypoxia or PGF2 alpha was completely inhibited by pretreatment with NO
      inhalation. Inhaled NO during maximal pressor response also depressed the
      elevated pressure to the basal level. These findings suggest that NO inhaled to
      the alveoli diffuses directly into the pulmonary vascular smooth muscle and then
      causes nonspecific vasodilation, and its effect is more potent than that of
      constitutive type of EDRF/NO.

PMID- 7739089
TI  - [MAC-awake and wake-up time of isoflurane and sevoflurane with reference to the
      concentration of gas, duration of inhalation and patient's age and obesity].
AB  - We evaluated the influence of the concentration of volatile anesthetics, the
      duration of inhalation time, the patient's age and degree of obesity on MAC-awake
      (the end-tidal concentration of volatile anesthetics on awakening) and Wake-up
      time (the period from stopping inhalation to eye-opening in response to verbal
      command) following isoflurane (Iso) or sevoflurane (Sev) anesthesia in 240
      patients (ASA I or II, age 17-84 yr). The patients were anesthetized with 50%
      oxygen, 50% nitrous oxide and various concentrations of Iso or Sev. They were
      divided into 6 groups in respect to the end-tidal concentration of Iso or Sev:
      Iso 0.7% (1 MAC), Iso 1.0% (1.5 MAC), Iso 1.4% (2 MAC), Sev 0.9% (1 MAC), Sev
      1.3% (1.5 MAC) and Sev 1.8% (2 MAC). After operation all anesthetics were
      discontinued and MAC-awake and Wake-up time were measured under 100% oxygen
      inhalation. MAC-awake value of Iso was 0.14 +/- 0.05% (SD)% in all groups and
      that of Sev was 0.17 +/- 0.05% in Sev 0.9% group, 0.16 +/- 0.05% in Sev 1.3%,
      0.17 +/- 0.06% in Sev 1.8%, respectively. All of them became smaller in aged
      groups than in younger groups but they were not influenced by the concentration
      of gas, the duration of inhalation nor the degree of obesity.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7739090
TI  - [Effects of bupivacaine on Na+ and Ca2+ currents in single canine ventricular
      cells].
AB  - The effects of bupivacaine on Na+ and Ca2+ currents in single canine isolated
      left ventricular cells were examined using whole-cell voltage clamp technique to
      reveal the mechanism of its negative inotropism. The cells were isolated by
      enzymatic dispersion and superfused in an oxygenated Tyrode's solution.
      Bupivacaine 10(-6) M decreased the amplitude of INa and delayed the peak time.
      These effects were dose and frequency dependent. At a concentration of 10(-3) M,
      bupivacaine abolished INa. Meanwhile, bupivacaine did not modify ICa at a
      concentration of 10(-6) M. At 10(-5) M bupivacaine, the amplitude of ICa was
      depressed by 22% and the depression was dose dependent. These results suggest
      that low concentration (10(-6) M) of bupivacaine depresses contraction, by
      reducing intracellular Ca2+ secondary to reduction in intracellular Na+ activity
      and the Na+-Ca2+ exchange mechanism. At higher concentrations, the reduction in
      contraction caused by bupivacaine may result partly from a reduced influx of
      Ca2+.

PMID- 7739091
TI  - [Analysis of the anesthesiologists' action patterns concerning regulation of the
      blood pressure and the concentration of inhalational anesthesia].
AB  - The action pattern of each anesthesiologist is different. We have developed a
      computer program simulating anesthesiologists' action patterns during operation
      and have extracted the action patterns of anesthesiologists using a computer
      program. The simulation program was designed to gather data on anesthesiologists'
      response to the change in blood pressure. The results indicate that the action
      pattern differs significantly from one anesthesiologist to another in responding
      to the change in blood pressure. That of one particular anesthesiologist remained
      the same, regardless of the agent used. His action pattern is directed only by
      the value of MAC and according to his own personal principle.

PMID- 7739092
TI  - [Measurements of ventilatory parameters during closed circuit anesthesia-
      comparisons with semiclosed circuit, high-flow anesthesia].
AB  - Since induction of anesthesia using a closed-circuit technique is difficult with
      most modern anesthesia machines, it is a common clinical practice to convert
      semiclosed, high-flow anesthesia (SCA) to closed circuit anesthesia (CCA) during
      the maintenance phase by decreasing the fresh gas flow. The purpose of the
      current studies was to determine if such changes in the fresh gas flow influence
      parameters of ventilatory dynamics. The tidal volume, airway pressure, and a
      ratio of expiratory volume in one second to a tidal volume (EV1.0/VT) were
      measured in six patients and in a lung simulator during CCA with a fresh gas flow
      of 200 ml.min-1 and SCA with a flow of 6 l.min-1. The ventilator settings were
      constant throughout the experiments. Dynamic compliance was calculated as
      (measured VT)/(peak airway pressure-positive end-expiratory pressure). Both in
      patients and in a lung simulator, dynamic compliance and EV1.0/VT were higher
      during CCA as compared to SCA while the tidal volume and airway pressure were
      lower. It was also suggested that these differences were secondary to differences
      in the fresh gas flow and not to the circuit situation (closed vs. semiclosed)
      per se. The results emphasize that the fresh gas flow should be taken into
      consideration in interpreting the data of ventilatory dynamics during anesthesia.
      This is especially so during CCA because CCA employs a minimum fresh gas flow.

PMID- 7739093
TI  - [Postoperative pain relief by patient controlled analgesia using intravenous
      pentazocine].
AB  - Patient controlled analgesia (PCA) by intravenous pentazocine was performed to
      determine its efficacy and the dose required for the pain relief after
      gynecological or obstetric operations. After obtaining informed consent, studies
      were performed on 28 female patients (ASA I, II: Mean age 38.1 years: Mean
      weight, 53.8 kg) who had received gynecological or obstetric operations with
      lower abdominal incision. Anesthesia given was nitrous oxide and isoflurane
      combined with epidural anesthesia with 1% mepivacaine used only during the
      operation. Six patients had cesarian section under spinal anesthesia. No patients
      received opioid during anesthesia. PCA was performed with a Graseby PCA pump.
      Lockout time was 8 minutes and the bolus dose was 3 mg. In all the patients,
      satisfactory pain relief was obtained and no other analgesic was necessary. Mean
      initial dose was 169.4 micrograms.kg-1 and the mean doses used for following each
      6 hours until 24 hours were 409.7, 368.6, 279.3 and 211.1 micrograms.kg-1
      respectively. Evaluation of PCA by the patients after the procedure showed
      excellent (13 patients) good (12) and passable (3) analgesia. No significant
      complication was observed except temporary nausea in two patients. Satisfactory
      postoperative pain relief could be obtained by relatively small doses of
      pentazocine and adverse reactions related especially to sigma receptor could be
      avoided.

PMID- 7739094
TI  - [Halothane reduces the inhibition of dorsal horn lamina V type neuronal activity
      induced by bradykinin injection into the femoral artery contralateral to the
      recording site].
AB  - Effect of halothane (0.2%, 0.5%, and 1.0%) on spinal function were studied in
      lamina V type cells responding to noxious and light touch applied at their
      cutaneous receptive field on the foot pad of the left hind paw. Extracellular
      unit activities of lamina V type cells were recorded at the lumbar level in six
      cats and thirteen spinal cats. When intra-arterial injection of bradykinin (BK)
      10 micrograms into the femoral artery ipsilateral to the recording sites was used
      as the noxious test stimuli, six of these cells (100%) were found to have
      inhibitory response in six intact cats and thirteen of these cells (100%) were
      found to have excitatory response in thirteen spinal cats. On the other hand,
      when the injection of 10 micrograms into the femoral artery contralateral to the
      recording sites was used as the noxious test stimuli, six of these cells (100%)
      were found to have inhibitory response in six intact cats and six of these cells
      (46%) were found to have inhibitory response in thirteen spinal cats. We studied
      the effect of halothane on the inhibition induced by BK injection into the
      femoral artery contralateral to the recording sites in six intact cats and six
      spinal cats. Halothane 0.2%, 0.5% and 1.0% reduced the inhibition of dorsal horn
      lamina V type neuronal activity induced by BK injection.

PMID- 7739095
TI  - [How should we treat intestinal ischemia?--II: Effects of pentoxifylline,
      glucagon and prostaglandin E1].
AB  - It is important to repair or ameliorate the intestinal ischemia in critically ill
      patients. Recent study of our suggests the superiority of dobutamine, but not
      dopamine, in improving the intestinal oxygenation. In this study we examined the
      effects of pentoxifylline (PF), glucagon (GL) and prostaglandin E1 (PGE1) during
      reduced blood flow of the superior mesenteric artery (SMA) in 20 anesthetized
      dogs. As an index of the intestinal oxygenation, tonometrically measured
      intestinal intramural pH (pHi) was used. A tonometer was inserted into the
      midjejunum through enterotomy. The SMA blood flow was measured by a transit-time
      flow meter. A vascular screw clamp for blood flow reduction was placed around the
      origin of the SMA, proximal to the flow probe. The SMA blood flow was adjusted to
      70% of baseline for three hours. After two hours of decreased blood flow, pHi
      dropped significantly from baseline. Then, either PF (20 mg.kg-1.min-1 over 10
      min, followed by 0.1 mg.kg-1.min-1), GL (1 microgram.kg-1.min-1) or PGE1 (0.05
      and 0.5 microgram.kg-1.min-1) was infused intravenously for one hour. With
      infusions of GL and large dose of PGE1, pHi tended to decrease further, although
      GL increased the cardiac output. Small dose of PGE1 had no significant effect on
      pHi. PF treatment showed beneficial effects not only on the cardiac output and
      the SMA blood flow, but also on pHi. We conclude that PF therapy may restore the
      intestinal microvascular blood flow. Further study of the effects of PF on tissue
      oxygenation and blood rheology is warranted.

PMID- 7739096
TI  - [Pulmonary hypertensive responses to erythrocytes components in sensitized
      rabbits].
AB  - Antigen erythrocytes cause a transient pulmonary hypertension in sensitized
      rabbits. We investigated the main responsible component in the antigen
      erythrocytes. Eleven rabbits were immunized intravenously with human O-N type
      erythrocytes every ten days until the agglutinin titer = 1:8,000 was obtained.
      Another ten rabbits without immunization served as a control group. Human
      erythrocytes were osmolitically hemolyzed and then separated into hemoglobin and
      membrane components by centrifugation. In sensitized rabbits, a bolus injection
      of human hemoglobin 0.7 ml.kg-1 caused increases in pulmonary arterial and airway
      pressures within 3-4 min. Increase in pulmonary arterial pressure after injection
      of hemoglobin component was significantly higher than that after injection of
      membrane component in sensitized rabbits. However, in nonsensitized rabbits both
      components were ineffective. Leukocytes counts decreased by 73-62% in sensitized
      rabbit, while they decreased by 16-37% in nonsensitized rabbits 5 min after
      injection of hemoglobin or membrane component. Platelets decreased by 54-61% in
      sensitized rabbits, while they decreased by 24-9% in nonsensitized rabbits 5 min
      after injection of hemoglobin or membrane component. We conclude that hemoglobin
      is the responsible component in the antigen erythrocytes and chemical mediators,
      such as thromboxane and platelet activating factor, may not be released from
      platelets and leukocytes.

PMID- 7739097
TI  - [Comparison of intubating condition under sevoflurane and halothane anesthesia in
      pediatric patients].
AB  - We compared intubating conditions under sevoflurane (group S) and halothane
      (group H) anesthesia in pediatric patients for otorhinolaryngological surgery.
      One hundred and six patients were divided randomly into group S (n = 60) and
      group H (n = 46). Anesthesia was induced with nitrous oxide-oxygen-sevoflurane
      (GOS, end-tidal sevoflurane concentration; 4.5%) or nitrous oxide-oxygen
      halothane (GOF, end-tidal halothane concentration; 1.6%). Intubating conditions
      were assessed according to the intubation score, which consists of the following
      three factors; mouth opening, visibility of vocal cord and body movement. Each
      factor is divided into three grades (0, 1, 2); total scores of 0 correspond to
      excellent. In comparing the groups with respect to anesthetic induction, group S
      required 180 sec for disappearance of spontaneous breathing and 660 sec for
      completion of intubation, while, in group H, the above time intervals were 188
      and 676 sec, respectively. We achieved significantly better intubating conditions
      in group H than group S. There were significantly more cases in group S than in
      group H in which vocal cord visibility was insufficient. Body movement during
      intubation was observed in 27% and 26% of patients in group S and H,
      respectively. In conclusion, halothane anesthesia provides better intubating
      conditions than sevoflurane anesthesia in slow induction for pediatric patients.

PMID- 7739098
TI  - [Improvement of cerebral oxidative metabolism and cytochrome aa3 redox state by
      7.5% hypertonic saline during hemorrhagic hypotension in dogs].
AB  - Our previous study reported that 20% (1.5 ml.kg-1 hypertonic saline could
      significantly improve the disturbances of cerebral oxidative metabolism induced
      by hemorrhagic hypotension in dogs. The aim of the present study is to evaluate
      if 7.5% hypertonic saline induces circulatory improvement. Ten dogs were randomly
      divided into two groups of 5 each resuscitated with either physiological saline
      as control or 7.5% hypertonic saline (4 ml.kg-1) after their mean arterial blood
      pressure decreased to 35 mmHg for 45 minutes by hemorrhage. The changes of
      cerebral tissue oxy- and deoxyhemoglobin, cerebral blood volume (total
      hemoglobin), and oxy-cytochrome aa3 were continuously monitored by near infrared
      spectroscopy throughout the experiment. The experimental result showed that oxy
      hemoglobin, oxy-cytochrome aa3, and cerebral blood volume decreased but
      deoxyhemoglobin increased significantly 45 minutes after hemorrhage. Treatment
      with 7.5% hypertonic saline significantly restored these variables except for
      cerebral blood volume and all the animals survived to the end of experiment. But
      in the control group treated with the same dose of physiological saline, the
      above variables improved little compared with the baseline; and all the animals
      died before the end of 60 min experimental observation. Therefore we conclude
      that 7.5% hypertonic saline (4 ml.kg-1) can also effectively improve the
      disturbance of cerebral oxidative metabolism induced by hemorrhagic hypotension.

PMID- 7739099
TI  - [Diagnosis of accidental subdural block].
AB  - Accidental subdural block occurred in a 47-year-old man who underwent gastrectomy
      under nitrous oxide-sevoflurane anesthesia combined with continuous epidural
      block. The development of subdural block was suspected from unexpectedly severe
      hypotension with small doses of mepivacaine during operation and was confirmed by
      a characteristic X-ray photograph after operation. The subdural block should be
      suspected from abnormal changes in vital signs and by careful observation of X
      ray photographs, because it is not always easy to determine the presence of
      contrast media either in the subdural space or in the epidural space.

PMID- 7739100
TI  - [The catecholamine concentrations of collected autologous blood during
      adrenalectomy for pheochromocytoma].
AB  - We studied the catecholamine concentrations in collected autologous blood of a
      patient undergoing adrenalectomy for pheochromocytoma. In the preoperative
      laboratory data, plasma concentrations (normal ranges) of epinephrine,
      norepinephrine and dopamine were 60180 pg.ml-1 (< 100), 11090 pg.ml-1 (100-450)
      and 104 pg.ml-1 (< 20), respectively. The catecholamine levels of collected blood
      were epinephrine 2490000 pg.ml-1, norepinephrine 352300 pg.ml-1 and dopamine 6100
      pg.ml-1 before wash. Wash of collected blood with 1000 ml saline diluted the
      catecholamines to epinephrine 212000 pg.ml-1, norepinephrine 18700 pg.ml-1 and
      dopamine 4900 pg.ml-1. Platelet activation by contact with tissue collagen or
      thrombin results in the release of catecholamine concentrated in the dense body.
      The mechanical stimulation by suction, roller pump and centrifugation during
      blood collection may accelerate the catecholamine release from platelets. Thus,
      saline wash hardly reduces catecholamine concentrations of collected blood from a
      patient with pheochromocytoma. In this particular case, plasma catecholamines
      seem to exceed the potential capacity of platelets in amount. The dilution effect
      for epinephrine and norepinephrine probably reflects the washout of greater
      amount of plasma catecholamines. However, saline wash was unable to reduce
      catecholamines contained in the collected blood to a safe level, and hypertension
      following autotransfusion was predictable. We conclude that hemodynamic change
      should be monitored carefully during intraoperative autotransfusion in a case of
      pheochromocytoma.

PMID- 7739101
TI  - [Anesthesia in a patient with epidermolysis bullosa].
AB  - A 6-year-old-boy with epidermolysis bullosa underwent plastic surgeries for the
      scar contraction of hands. Anesthesia was induced with inhalation of sevoflurane
      in combination with nitrous oxide and oxygen. The tracheal was not intubated.
      Anesthesia was maintained with sevoflurane, nitrous oxide and oxygen with
      continuous intravenous infusion of ketamine. The courses of anesthesia and the
      operations were uneventful. The most important point in the anesthetic management
      of the patient with this disease is to avoid mechanical stimulation to skin and
      mucous membrane.

PMID- 7739102
TI  - [The efficacy of midazolam-famotidine suppository for premedication in children].
AB  - We evaluated the efficacy of midazolam-famotidine suppository (M-F suppository)
      for premedication in children. After obtaining informed parental consent, we
      studied children aged 5m-7y, ASA I status, scheduled for minor elective surgery.
      The suppository group (n = 26) was given suppository of both midazolam 0.5 mg.kg
      1 and famotidine 2 mg.kg-1, and the intramuscular injection group (n = 19) was
      given hydroxyzine 1 mg.kg-1. In the suppository group, gastric pH (3.90 +/- 0.34)
      was significantly higher, and gastric volume (1.88 +/- 0.54 ml) was significantly
      less than in the intramuscular injection group (1.82 +/- 0.15, 8.42 +/- 1.76 ml).
      The M-F suppository may offer similar sedative effect as an intramuscular
      injection of hydroxyzine. We concluded that the M-F suppository is an effective
      premedicant for pediatric patients.

PMID- 7739103
TI  - [Patient's complaints preceding severe bradycardia and hypotension during spinal
      anesthesia].
AB  - We reported an episode of sudden bradycardia and hypotension during spinal
      anesthesia, in which the patient complained of nausea before the bradycardia and
      hypotension were recognized by the monitors, such as, intermittent measurement of
      arterial pressure, electrocardiography, pulse oxymetry and continuous arterial
      blood gas analysis. We emphasize the importance of strict vigilance during spinal
      anesthesia.

PMID- 7739104
TI  - [Chest pain in a patient after median sternotomy].
AB  - A 62-year-old woman presented with a 1-year history of painful operative scar
      following median sternotomy performed for coronary artery bypass grafting at
      another hospital shortly after myocardial infarction. She had a 5-year history of
      diabetes mellitus, which had been controlled with diet therapy. There were no
      abnormalities in electrocardiographic or cardiac function. She complained of
      burning pain and marked tenderness bilaterally in the parasternal region. There
      were no abnormal laboratory findings. No fractures were detected in the ribs or
      sternum radiographically. Her chest pain was not alleviated by analgesics
      including nonsteroidal anti-inflammatory agents or tricyclic antidepressants.
      Neither local anesthesia nor thoracic epidural anesthesia was effective in
      eliminating her pain. Slight relief was obtained by heating with infrared
      radiation, but the duration of pain relief was very short. This patient's
      findings indicate that painful operative scar should be considered as a
      potentially serious complication of surgery requiring median sternotomy.

PMID- 7739105
TI  - [Hemodynamic and blood gas changes during femoral neck prosthetic replacement
      using a cement gun].
AB  - We investigated hemodynamic and blood gas changes in eight patients undergoing
      femoral neck prosthetic replacement. We measured blood pressure, heart rate,
      pulmonary artery pressure, cardiac output and blood gas before packing bone
      cement with a cement gun and 5, 10, and 15 min after the insertion of the
      prosthesis. Significant increases in mean pulmonary artery pressure, and arterial
      PCO2 were observed, but there were no significant changes in mean arterial
      pressure, cardiac output, or arterial PaO2. These pulmonary circulatory and blood
      gas alterations suggested that pulmonary embolism or pulmonary vasospasm had been
      brought about by the insertion of the prosthesis, but this did not result in
      systemic changes in the patients in this study. In conclusion, it is recommended
      to monitor circulatory and respiratory changes closely to detect pulmonary
      embolism during femoral neck prosthetic replacement using a cement gun.

PMID- 7739106
TI  - [Anesthetic management of a patient with urticaria pigmentosa].
AB  - Urticaria pigmentosa is a usually a benign and asymptomatic cutaneous variant of
      mastocytosis, which is a relatively rare disorder characterized by abnormal
      aggregates of mast cells in the dermis. These aggregations, if present, can
      abruptly release vasoactive mediators such as histamine, heparin, and
      prostaglandins under some physical stresses and may produce flushing,
      hypotension, syncope, shock, etc. One of the interesting aspects to an
      anesthesiologist is the effect of drugs administered perioperatively on mast cell
      degranulation. We report an infant case of urticaria pigmentosa and discuss the
      anesthetic significance especially of mastocytosis during anesthesia and surgery.

PMID- 7739107
TI  - [Anesthetic management of a patient with Cowden syndrome].
AB  - Cowden syndrome is a rare syndrome of chromosome abnormalities presenting with
      polyposis of digestive tracts, characteristic skin eruption and neuromuscular
      disorders. A 56-year-old male patient with Cowden syndrome underwent upper
      abdominal surgery under general anesthesia followed by post-operative epidural
      analgesia with buprenorphine. Proposed total gastrectomy was not performed
      because of massive invasion of carcinoma in the abdominal cavity and
      gastrojejunostomy was done instead. The anesthesia was satisfactory with
      inhalation of nitrous oxide and enflurane with intravenous vecuronium.
      Neuromuscular monitoring with electric twitch-responses of the hand showed normal
      patterns throughout the anesthesia. The recovery from anesthesia and
      neuromuscular blockade was prompt. Intermittent epidural buprenorphine, twice a
      day (0.2 mg of buprenorphine in 9 ml of normal saline for one time) was started
      just after the recovery of anesthesia and continued for four days. Delirium
      occurred two days after beginning epidural buprenorphine and disappeared three
      days after its discontinuation. The patient died 52 days after the operation from
      obstructive jaundice and sepsis. The delirium, therefore, seems to have been
      caused by buprenorphine possibly due to its impaired metabolism by the liver.
      Although we did not experience any abnormal neuromuscular reactions to vecuronium
      or anesthetic agents, it is important to perform preoperative neuromuscular
      examinations and peri-operative monitoring in the anesthetic management of a
      patient with this syndrome.

PMID- 7739108
TI  - [Cytokines in laboratory medicine].
AB  - A cytokine was first recognized in 1965, and many kinds of cytokines have been
      found since then. Cytokines are the biologically active substances which are
      produced in immuno-competent cells, macrophages and monocytes, excluding
      immunoglobulins. They form complex networks among themselves, and mainly act
      locally. A single cytokine may have physiological actions to many different
      cells, while a certain physiological action may be shared by many different
      cytokines. Some of them could be now quantitated immunochemically by using highly
      sensitive immunoassays. Therefore, immunoassay of some cytokines may become very
      important in laboratory medicine.

PMID- 7739109
TI  - [Laboratory medicine of lymphocytes].
AB  - Recently, many laboratory tests associated with lymphocytes and/or lymphocyte
      functions have been developed. Among them, cytokine determinations of various
      body fluids and cytokine production assays are most highlightened. As cytokine is
      an effector molecule in immunological network, cytokine production profile may
      indicate functional state of immune response and immunopathological process. On
      the basis of these understandings, we propose cytokine production assay of whole
      blood culture system.

PMID- 7739111
TI  - [Interleukin-8].
AB  - Interleukin 8 (IL-8) is one of the most widely studied chemoattractants for
      leukocytes. It belongs to the newly classified CXC family of chemokine which
      possesses biological activities mainly on neutrophils. The potential role of IL-8
      in inflammation is substantiated by the growing evidences of clinical relevance
      of IL-8 in various diseases such as infection, ischemia and autoimmune disorders.
      The common characteristic pathological feature of these events is neutrophil
      infiltration. Although little is known about the mechanism of neutrophil
      recruitment into the urine, urinary tract infections (UTI) are accompanied by
      pyuria. Elevated urinary IL-8 levels were found in patients with UTI. Bioactive,
      multiple forms of IL-8 were produced locally within the urinary tract, and
      implied that IL-8 participated in the induction of neutrophil migration into the
      inflammatory site. Similar findings were observed in the peritoneal dialysate of
      patients on continuous ambulatory peritoneal dialysis with peritonitis. The
      notion of involvement of IL-8 in local infection was reinforced by the findings
      obtained on the rabbit UTI model. Finally, the clinical usefulness, as well as
      the problems of IL-8 level determination in various body fluids are discussed.

PMID- 7739110
TI  - [Cytokine assays].
AB  - There is growing interest in the use of immunoassays or bioassays for the
      measurement of cytokines in body fluids in the assessment of disease. Since
      bioassays are time-consuming and have problems of reproducibility and
      specificity, the ELISA method, including commercially available kits, is
      currently in widespread use. The results of cytokine measurements by these ELISA
      kits have been found to be consistent and reproducible. However, the detection
      limit of these kits for almost all cytokines is not sensitive enough to measure
      cytokine levels in various body fluids in which picogram levels of cytokine
      variation may be significant. In addition, the effects of soluble cytokine
      receptors and inhibitors in body fluids on the results of cytokine measurements
      determined by the ELISA system remain to be clarified. Cytokines have been
      measured in clotted serum. However, because the serum generates a variety of
      proteases, the clotting of blood may affect the basal levels of cytokines in the
      blood. The blood collected in EDTA may be optimal for measuring circulating
      cytokine levels in blood, as compared with other commonly used anticoagulant
      methods of blood collection. The measurement of cytokines in body fluids has been
      of clinical value in several area, including (1) the indication of disease
      activity and response of therapy in certain diseases, (2) the prediction of
      prognosis in certain diseases, (3) providing possible explanations for the
      mechanisms of tissue damage in certain diseases, and (4) the elucidation of
      pathogenesis of certain diseases.

PMID- 7739112
TI  - [Molecular biology in cardiovascular medicine].
AB  - Molecular biology has given a strong impact on cardiovascular medicine, not only
      clinical but also laboratory medicine. cDNA cloning and analysis of gene
      structures encoding functional proteins or peptides in the cardiovascular system
      provided insight into molecular mechanisms underlying heart diseases or
      atherosclerosis. Nucleotide or amino acid sequences for these molecules are
      useful information for manufacturing bioactive peptides or developing
      immunoassays. These cDNA clones or genes are useful molecular tools diagnosing
      patients with high risks for cardiovascular diseases. Recent advances in this
      field have been made in identification of point mutations of many genes important
      for cardiovascular functions, including LDL receptors in familial hyperlipidemia,
      cardiac myosin heavy chain genes in familial hypertrophic cardiomyopathy,
      mitochondrial DNA in mitochondria cardiomyopathy, or dystrophin genes in
      secondary cardiomyopathy. Molecular probes are further used in detection of
      microorganisms causing myocarditis. These progresses that have been made in
      laboratories of basic researchers will be introduced into clinical medicine and
      expand the field the laboratory medicine is involved.

PMID- 7739113
TI  - [Smooth muscle myosin heavy chain expression in the arterial wall; a new
      viewpoint for vascular pathology].
AB  - Smooth muscle is an important component of the vessel wall. Smooth muscle cell
      undergoes phenotypic modulation during development of vascular lesions, such as
      atherosclerosis and restenosis following percutaneous transluminal coronary
      angioplasty (PTCA). In order to understand the mechanism of vascular remodeling,
      it is important to identify the smooth muscle cell in the vascular lesion and
      identify its phenotype by using molecular markers specific to the smooth muscle
      cell. Three types of myosin heavy chain (MHC) isoforms (SM1, SM2 and SMemb)
      expressed in smooth muscles are suitable for this purpose. In this study we first
      demonstrated that the expression of smooth muscle specific MHCs, such as SM1 and
      SM2, is reduced in human coronary arteries after the fifth decade. On the other
      hand, rapidly proliferating smooth muscles in the restenotic lesion express
      abundant SMemb but less amount of SM2. These observations indicate that deranged
      vascular smooth muscle differentiation is involved the development of vascular
      lesion. We furthermore demonstrated that smooth muscle-specific MHC is released
      into serum from the arterial wall following vascular damage as in dissecting
      aneurysm. Circulating smooth muscle MHC level was elevated 5-10 times above
      normal at 24 hours after aortic dissection as determined using a sensitive ELISA.
      We conclude from these results that smooth muscle MHC isoforms are important
      molecular markers for vascular pathology as well as for biochemical diagnosis of
      vascular injuries.

PMID- 7739114
TI  - [Molecular genetics of cholesterol transport and cholesterol reverse transport
      disorders (familial hypercholesterolemia and CETP deficiency), and coronary heart
      disease].
AB  - Familial hypercholesterolemia (FH) is a disorder of LDL receptor abnormalities,
      and the resultant high-LDL-cholesterolemia produces atherosclerosis. More than
      150 different mutations in the LDL receptor gene have been reported in the world.
      Seven variants of the LDL receptor gene have been identified in our laboratory.
      These seven mutants in 85 patients from 31 families accounted for only 15.5% of
      the FH cases. LDL receptor gene abnormalities are highly heterogenous in Japan,
      and the variation of the LDL receptor mutant may determine the severity of
      hypercholesterolemia and coronary heart disease in FH. A serum HDL above 60 mg/dl
      is a negative risk factor for coronary atherosclerosis. We found that familial
      hyperalphalipoproteinemia can be produced by CETP deficiency due to a CETP gene.
      Two common mutants of the CETP gene produce a CETP deficiency and resultant
      antiatherogenic lipoprotein pattern (i.e. hyper-HDL-cholesterolemia and hypo-LDL
      cholesterolemia), and the frequency of the mutant allele is more than 1 in 10
      subjects in Japan. Finally, we found unique patients with double heterozygotes of
      FH and CETP deficiency. We found 16 double heterozygotes of the LDL receptor gene
      and CETP gene. Four of the 16 patients showed myocardial infarction and 4 showed
      angina pectoris. These findings suggest that the atherogenicity of hyper-LDL
      cholesterolemia in FH is more powerful than antiatherogenicity of hyper-HDL
      cholesterolemia in CETP deficiency.

PMID- 7739116
TI  - [Genetic linkage analyses of Romano-Ward syndrome (RWS) in 13 Japanese families].
AB  - Romano-Ward syndrome (RWS) is an autosomal dominant disorder characterized by
      prolongation of the electrocardiographic QT interval, with clinical
      manifestations that include recurrent syncope and sudden death from ventricular
      arrhythmias. In order to find a long QT locus in Japanese patients and to
      identify DNA markers useful for presymptomatic diagnosis, linkage analyses were
      undertaken in 13 Japanese families with RWS patients by means of two DNA markers
      located on 11p15.5. One of these marker loci, HRAS, was previously reported to be
      tightly linked to the LQT locus in another ethnic group. Our analyses of
      homogeneity suggest evidence for genetic heterogeneity of RWS with the Japanese
      population.

PMID- 7739115
TI  - [Deletion polymorphism of the angiotensin I-converting enzyme gene associates
      with increased risk for ischemic heart diseases in the Japanese].
AB  - The Angiotensin I-converting enzyme (ACE) is a key component of the renin
      angiotensin system thought to be important in the pathogenesis of hypertension
      and cardiovascular diseases. Previous studies showed that deletion polymorphism
      in the the ACE gene might be a risk factor for myocardial infarction in the
      Caucasian population, but, this finding has not yet been reported in a Japanese
      population. In this study, a 287 base pair (bp) insertion/deletion polymorphism
      in intron 16 of the ACE gene was examined by the polymerase chain reaction (PCR)
      in a cross-sectional study of 100 healthy subjects and 218 patients with ischemic
      heart diseases (IHD) (70 angina pectoris, 148 myocardial infarction).
      Polymorphism of the ACE gene was characterized by three genotypes: two deletion
      alleles (genotype DD), two insertion allele (genotype II) and heterozygotes
      alleles (genotype ID). No differences could be detected among the three genotypes
      for total cholesterol, high-density lipoprotein cholesterol, blood pressure and
      body mass index. The serum ACE activity in each II, ID and DD genotype was 11.4
      +/- 2:7 microU/ml, 14.5 +/- 3.5 microU/ml, 16.6 +/- 4.6 microU/ml, respectively.
      In the population study, genotype DD was significantly associated with IHD when
      compared with the other two genotypes (ID and II). The frequency of deletion
      allele was higher (0.56) in the IHD group than in the normal individuals (0.42)
      (p < 0.05). These frequencies were not varied whether they had classic risk
      factors or not. Furthermore, coronary multivessel impairment was significantly
      associated with a deletion allele than with an insertion allele (p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7739117
TI  - [Detection of viral genomes in myocarditis].
AB  - Although much evidence favors the concept that dilated cardiomyopathy could be a
      postviral disease, the actual prevalence and pathogenesis of viral heart disease
      in dilated cardiomyopathy has not been well explored, since the diagnosis of
      viral infection is still difficult. The recently developed polymerase chain
      reaction (PCR) has made it possible to amplify a few copies of viral genome and
      has shown that viral genomes persist long after viral infection. The PCR is a
      promising method for testing possible viral etiology. We have found that
      antiheart antibodies associated with a murine model of myocarditis increased the
      intracellular free Ca2+ concentration through the activation of Ca(2+)-permeable
      cation channels in isolated ventricular cells. Marked induction of Mn-SOD and
      Cu/Zn-SOD mRNA was found in the heart with viral myocarditis and oxygen radicals
      may play an important role in the pathogenesis of viral myocarditis. Our recent
      studies revealed an increase in the circulating cytokines in patients with acute
      myocarditis and cardiomyopathy and suggested that cytokines play some role in the
      pathogenesis of myocardial injury in these diseases. In our animal model of EMC
      virus myocarditis, plasma tumor necrosis factor (TNF)-alpha was elevated in the
      acute stage and exogenously administered anti TNF-alpha antibody improved the
      survival and myocardial lesion, suggesting the importance of TNF-alpha in the
      pathogenesis.

PMID- 7739118
TI  - [Molecular differential diagnosis of herpes virus using common primer pairs:
      detection of HSV-1, HSV-2, VZV and CMV by the PCR].
AB  - Differential diagnosis of herpes virus species is often required in various
      clinical courses, such as transplantation and immunocompromised patients. Pairs
      of common primers which enabled sufficient amplifying and differential diagnosis
      of herpes virus species were designed and nested PCR using the common primer
      pairs was conducted to evaluate for its clinical application. The PCR was shown
      to provide amplification and differential diagnosis of HSV-1, HSV-2, VZV and CMV.
      The results of the PCR were consistent with those from fluorescent antibody of
      herpes virus culture and isolation. From clinical vesicular specimens, the PCR
      enabled the direct detection of HSV-1, HSV-2, and VZV. The PCR using the common
      primer pairs offers speed in the differential diagnosing of herpes virus.

PMID- 7739119
TI  - [Newly developed detection system for serum Helicobacter pylori antibodies using
      ELISA and its clinical significance].
AB  - Using ELISA, a specific and sensitive system that detects serum immunoglobulin G
      antibodies against all soluble antigens of Helicobacter pylori (Hp) has been
      developed. This system is used at three different concentrations of Hp antigens
      coated on the solid phase of the ELISA. Anti-Hp antibodies were judged positive
      when the difference in the ELISA values between high and middle or middle and low
      concentrations of antigen were over the specific values. For the ELISA system,
      called the three point antigen method, sensitivity and specificity of urease
      activity were 86.9% and 70.8%, respectively. Positive rate for antibodies to
      serum Helicobacter pylori in dyspeptic patients was higher than that in healthy
      subjects.

PMID- 7739120
TI  - [Clinical and etiological studies of IgG antibodies to Helicobacter pylori
      detected by enzyme-linked immunosorbent assay].
AB  - Recently, Helicobacter pylori (H. pylori) has been reported that it is involved
      in the pathogenesis of duodenal ulcer and might be a risk factor for gastric
      cancer. To diagnose H. pylori infection, detection of serum antibody is much less
      stressful and more cost effective than gastric biopsy. Using a serological
      method, We have reported that the prevalence of serum anti-H. pylori IgG was
      elevated with age among healthy subjects and over 80% among elder people. Thus,
      it would be essential to investigate the specificity of the ELISA system
      (PirikaplateG Helicobacter) for the detection of serum anti-H. pylori IgG. Sera
      from healthy controls (n = 653) and patients (n = 116) with gastritis, gastric
      ulcer, and/or duodenal ulcer were studied for anti-H. pylori IgG. Cross
      reactivity of the anti-H. pylori IgG with closely related bacteria was less than
      10% (with C. jejuni: 7.4%, C. laridis: 0.2%, E. coli: -2.4%) in the ELISA system.
      Anti-H. pylori IgG from both normal controls and the patients were equally
      neutralized with the extract of H. pylori. Of note was that the prevalence of
      anti-H. pylori IgG among patients was significantly higher than that among normal
      controls. Referring to the diagnoses by gastric biopsy, the sensitivity and
      specificity of this ELISA were 88.2% and 74.2%, respectively. We also
      demonstrated the clinical usefulness of this ELISA by receiver operating
      characteristic curve (ROC). Interestingly, several healthy subjects positive for
      serum anti-H. pylori IgG were voluntarily subjected to gastric biopsy, and proved
      positive for H. pylori infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7739121
TI  - [Clinical significance of platelet volume indices estimated by automated blood
      cell analyzer].
AB  - Clinical significance of platelet volume indices (Platelet distribution width:
      PDW, Mean platelet volume: MPV, Platelet large cell ratio: P-LCR) estimated by
      automated blood cell analyzer (Sysmex NE-8000) was studied in 29 ITP cases and 17
      cases with platelet hypoproduction which diagnosis was established by platelet
      kinetic study, megakaryocyte counts and the amount of platelet-associated IgG.
      These indices were not obtained by analyzer in 48% of 23 cases with platelet
      count less than 50 x 10(9)/l and 23% of 31 cases with platelet counts ranged in
      50-100 x 10(9)/l. The coefficient of variation (CV) of PDW, MPV and P-LCR
      estimated 5 times in samples with platelet count more than 100 x 10(9)/l was 2%,
      1% and 2.3%, respectively. In samples with platelet count less than 50 x 10(9)/l,
      CV of each index increased 3 times or more. Only four out of 22 ITP cases with
      platelet count less than 100 x 10(9)/l showed increased platelet volume and
      remaining 18 cases showed normal volume. In 12 cases with platelet
      hypoproduction, 3 cases showed increase of platelet volume and one case showed
      decrease of volume. Significant correlation was observed in between PDW and
      platelet survival time (r = -0.41, p < 0.05) and in between PDW and platelet
      turnover rate (r = 0.38, p < 0.05) in 29 ITP cases. Although the various changes
      of platelet volume indices during recovery phase after chemotherapy were observed
      in cases of acute leukemia or malignant lymphoma, these one were not a
      characteristic change in recovery phase of platelet under-production but rather
      different in each individual.

PMID- 7739122
TI  - [Genetic analysis of the genotype of ABO blood group with the DNA from a hair].
AB  - The genotype of the hair genomic DNA from 14 subjects with the ABO blood group
      was determined using the polymerase chain reaction (PCR)-restriction fragment
      length polymorphism (RFLP) method. The amino acid substitutions of codon 87 and
      176 of ABO allelic cDNAs were analyzed to distinguish A, B, and O alleles by
      restriction enzyme digestion. To identify codon 87, the 249bp DNA fragment was
      amplified by PCR and digested with Kpn I. To identify codon 176, the 285bp DNA
      fragment was amplified by PCR and digested with Ban I. The genotype of the 14 ABO
      type-known subjects could be identified by the analysis of the digested DNA
      fragments. These findings indicate the usefulness of the PCR-RFLP method for
      determining the ABO genotype with the DNA from only one hair.

PMID- 7739123
TI  - [Clinical usefulness of polyamino acid particle agglutination test for detection
      of anti-HTLV-I antibody].
AB  - A new artificial carrier particle agglutination test using polyamino acid
      (polyamino PA) was developed for anti HTLV-I assay. We carried out the
      comparative study on anti-HTLV-I among polyamino PA, gelatin PA, EIA and WB
      methods. All of 76 ATL, 20 HAM/TSP, 53 patients with uveitis and 50 HTLV-I
      carriers were seropositive and 50 HTLV-I non carriers were seronegative with four
      methods. Eighteen of 503 patients include autoimmune diseases showed seropositive
      by polyamino PA and gelatin PA. One of 19 seropositives by EIA was false
      positive. All of 25 sera showed non-specific reaction by the gelatin PA were
      clearly negative by the polyamino PA. This is due to the fact that the polyamino
      acid particle has a greater specific gravity as carrier. The final judgement was
      got within 45 minutes. It was earlier more 30 minutes than the gelatin PA. The
      polyamino PA is a simple, rapid, sensitive and specific method. Therefore, it is
      useful for mass screening and clinical diagnosis.

PMID- 7739124
TI  - [Measurement of anti-acetylcholine receptor antibody using human rhabdomyosarcoma
      cell line].
AB  - We developed a radioimmunoassay for AChR Ab using AChR solubilized from membrane
      extracts of human rhabdomyosarcoma cell line (RD cell). The binding affinity of
      this AChR to the alpha-Bungarotoxin (alpha-BTX) was similar to that of AChR from
      cell surface. Lyophilized AChR was stable within two months at -20 degrees C. In
      our assay system, sera from patients with Myasthenia Gravis (MG) showed markedly
      high titers and frequency (94%) of anti-AChR Ab. On the other hand, almost all
      sera from normal and non-myasthenic patients such as rheumatoid arthritis and
      thyroid disease were negative (< 0.2nmol/l). Our assay using AChR from RD cells
      shows sufficient results in the intra- and inter-CV values, and recovery and
      dilution tests. AChR Ab titers of our assay showed good correlations with those
      measured by AChRs from both human ischemic muscles and TE671 cells (commercial
      kit). The radioimmunoassay for AChR Ab using the membrane extracts of RD cells
      has high sensitivity, specificity and stability. Therefore, the assay is valuable
      as the routine assay for the diagnosis of MG.

PMID- 7739125
TI  - [Experimental cancer of the digestive tract--cultured cells of human gastric
      cancer and tumor transplanted into nude mice].

PMID- 7739126
TI  - [Characteristics of early gastric cancer accompanied by lymph node metastasis].
AB  - We studied the phenotypic expression, DNA ploidy patterns and other clinico
      pathological features of early gastric cancers accompanied by lymph node
      metastasis. Of 241 cases studied, 18 (7.5%) were lymph node-positive.
      Histologically, 4 were tub1, 7 tub2, 4 sig and 3 por. Seven of the 18 were
      differentiated type cancers with accompanying undifferentiated type cancer cells
      in a part of the cancer tissue. Mucin histochemistry showed that 15 of the 18
      cancers were composed exclusively of gastric type cells, while the other 3 were
      composed of intestinal type cells. The incidence of gastric type cells in node
      positive cancers was significantly higher (p < 0.05) than that in node-negative
      cancers. All node-positive mucosal cancers were composed mainly of gastric type
      cells. These findings indicate that there are many cancers which are originally
      gastric in type, and that gastric type cancers readily develop lymph node
      metastasis. On the other hand, a cytofluorometric study showed that 10 tumors
      were diploid and 8 were aneuploid. There was no statistically significant
      association between DNA ploidy patterns and the occurrence of lymph node
      metastasis.

PMID- 7739127
TI  - [Characteristics and development of stump cancers of the stomach].
AB  - To clarify characteristics and development of stump cancers of the stomach, we
      studied 10 cases (12 lesions) of them with mucin-histochemical and
      immunohistochemical techniques and gene analysis using polymerase chain reaction.
      Sixty-seven % of the cancers were mostly composed of gastric-type cells and 67%
      also showed abnormal accumulation of p53 protein in their nuclei. There were
      scattered cells with abnormal accumulation of p53 protein in cystically dilated
      glands that were often found to be surrounding cancers. Immunohistochemistry of
      proliferating cell nuclear antigen also demonstrated proliferating activity of
      these cystic glands. It is suggested that the cystically dilatated gland is
      precancerous lesion of stump cancers of the stomach. The gene analysis showed
      less occurrence of K-ras abnormality, and the mutation of APC gene is suggested
      to be infrequent.

PMID- 7739128
TI  - [Predictable factors in healing of gastric ulcer, comparative analysis of local
      morphologic factor of gastric ulcer and suppression of intragastric pH].
AB  - Predictable factors in healing of 48 patients with gastric ulcer by PPI or H2-RA
      on 4 and 8 weeks of treatment were investigated. We evaluated the following
      factors such as patient's profile, local morphologic factors of gastric ulcer and
      suppression rate of 24 hr intragastric pH between healed and unhealed patients
      using single and multiple variable analysis. Results obtained from multiple
      variable analysis, the significant and independent factors of intractable gastric
      ulcers on the 4th week of treatment were ulcer size in over 20 mm and solitary
      ulcer. On the contrary, those of 8th week of treatment were shortage of holding
      time of intragastric pH over pH4 (less than 16.7 hrs) during treatment, the site
      of ulcer at lesser curvature of gastric angle and the shape of ulceration which
      showed mucosal overhanging. Considering with single and multiple variable
      analysis, we concluded that, in early phase, local shapes of the ulceration were
      important predictors in the healing of gastric ulcer, and the after that, the
      inhibition of intragastric acidity were significant factors in healing process of
      gastric ulcer.

PMID- 7739129
TI  - [A case of progressive systemic sclerosis complicated with pneumatosis cystoides
      intestinalis and pneumatoperitoneum which was clearly diagnosed by CT scan].

PMID- 7739130
TI  - [A rare case of true enterolith including a fruit seed].

PMID- 7739131
TI  - [A case of antiphospholipid syndrome associated with Buerger's disease and portal
      hypertension].

PMID- 7739132
TI  - [A case with well differentiated hepatocellular carcinoma of rapidly growing
      type].

PMID- 7739133
TI  - [A case of hepatocellular carcinoma, gastric cancer and adrenocortical cancer
      showing positive immunohistochemical staining of PIVKA-II on adrenocortical
      tissue].

PMID- 7739134
TI  - [A case of early gallbladder cancer resected after follow up for 8 years].

PMID- 7739135
TI  - [Efficacy of expandable metallic stent for a large stone in common bile duct:
      report of a case].

PMID- 7739136
TI  - [A case report of malignant lymphoma of the pancreas head with obstructive
      jaundice].

PMID- 7739137
TI  - [A case of portal vein thrombosis subsequent to acute pancreatitis].

PMID- 7739138
TI  - [Aging and disease in the elderly].

PMID- 7739139
TI  - [2000 femoral neck fractures of the aged].

PMID- 7739140
TI  - [Clinico-statistical study on tuberculous peritonitis and genital tuberculosis in
      elderly women].
AB  - We clinico-statistically studied 8 patients (0.77%) with tuberculous peritonitis
      (3 cases) and tuberculous endometritis (5 cases) aged 50 or older who visited our
      gynecological clinic for 6 years from July, 1986 to June, 1992 in Tokyo
      Metropolitan Tama Geriatric Hospital. The mean age was 72 years with a range of
      52 to 82 years. Five cases with tuberculous endometritis were diagnosed based on
      the findings of endometrial cytology and bacteriology, and the incidence was
      0.93% of 535 cases in which the uterine cavity could be examined. Three cases
      with tuberculous peritonitis were strongly suspected by the ascitic findings
      (cytology and adenosine deaminase level), and culture of ascitic fluid for acid
      fast bacilli was positive in 2 of the three cases. Another case with negative
      culture was diagnosed based on the marked improvement of clinical findings and
      symptoms during chemotherapy for tuberculosis. No cases were complicated by
      active lung tuberculosis. All cases had a family and/or past history of pulmonary
      tuberculosis. The PPD skin test was positive in 7 of the 8 cases. In all cases,
      the clinical laboratory data and symptoms were markedly improved by chemotherapy
      for tuberculosis. Endometrial cytology and transvaginal ultrasonography were very
      effective methods for the diagnosis of tuberculous endometritis and peritonitis
      associated with ascites.

PMID- 7739141
TI  - [Studies on atrial arrhythmias in atrial septal defect. The influences of aging
      on atrial fibrillation].
AB  - Clinical characteristics of aging in congenital atrial septal defect (ASD)
      without significant right-to-left shunt (> 10%), were examined especially
      focusing on atrial arrhythmias such as atrial fibrillation (Af) and atrial
      premature contraction (PAC) in serial 48 patients, aged 42.6 +/- 2.3, ranging 16
      67 years, Af was found in 12 (25%) out of 48 patients. Comparing patients with Af
      and those without Af, the average age (52.8 +/- 2.6 vs 38.6 +/- 2.8 years, p <
      0.05), functional class of New York Heart Association (2.0 +/- 0.2 vs 1.6 +/-
      0.1, p < 0.05) and left atrial dimension (41.4 +/- 1.1 vs 34.7 +/- 1.2 mm, p <
      0.01) were significantly higher in the patients with Af than those without Af.
      Hemodynamic variables, i.e., mean right or left atrial pressure, Pp/Ps, Qp/Qs,
      left-to-right shunt, electrocardiographic R/S ratio in the lead V1 and tricuspid
      regurgitation had no relation either with aging or Af. Furthermore, daily PAC
      counts on Holter electrocardiograms significantly correlated with the age of the
      patients (r = 0.642, p < 0.05). These results suggest that the incidence of Af in
      congenital ASD is significantly related with aging/duration of ASD, but not with
      hemodynamic variables.

PMID- 7739142
TI  - [Intracystic infusion therapy of minocycline hydrochloride for benign hepatic
      cysts].
AB  - This paper describes ultrasonically-guided infusion of minocycline hydrochloride
      solution (MINO infusion therapy) in benign nonparasitic cysts of the liver. MINO
      infusion therapy was performed in 7 large hepatic cysts and successful results
      were obtained in 6 lesions. The infusion procedure in the initial 4 hepatic cysts
      a 7 Fr catheter was placed into the cyst and MINO solution was left in the cyst
      according to the procedure of ethanol infusion therapy. In the most recent 2
      cases the cyst was punctured with a 21G needle, washed with physiologic saline
      and then infused MINO solution without placement of an indwelling drainage tube.
      This modified procedure is simple and safe and also yields a good therapeutic
      result. MINO infusion therapy for benign hepatic cyst is very useful and the
      modified procedure can be performed safely in elderly patients and in patients
      with several complications.

PMID- 7739143
TI  - [An epidemiological study of stroke in a geriatric community--with special
      reference meteorological factors].
AB  - The incidence of cerebrovascular event during a period of 3 years in the
      geriatric society in Japan was examined along with the alternating pattern of
      cerebrovascular accidents in relation to aging and seasonal factors. The
      population of Tsuwano town was approximately 7000. The percentage of aged people
      over 65-year-old reached 23.1% in the 1990 national census. All cerebrovascular
      accident patients in our hospital and two outpatients clinic in this city were
      registered during the period from April, 1990 to March, 1993. The number of
      patients in the period was 95 cases, of which 19 were classified as transient
      ischemic attack (TIA), 30 as cerebral thrombosis, 16 as cerebral embolism, 10 as
      cerebral hemorrhage, 7 as subarachnoid hemorrhage, and 13 as unclassified
      cerebral infarction. The frequency of each type except TIA was 39.5% cerebral
      thrombosis, 21.1% cerebral embolism, 13.2% cerebral hemorrhage, and 9.2%
      subarachnoid hemorrhage. In all cases, hypertension was observed in 62.1%, and
      past history of cerebrovascular accident was observed in 29.5%. The cerebral
      embolism group was older than the other groups and one-half of this group had
      atrial fibrillation. Peak incidence differed by type of illness, TIA and cerebral
      embolism occurred uniformly throughout the year, but subarachnoid hemorrhage and
      cerebral thrombosis in the spring. The relationship of cerebrovascular accident
      to crisis, especially potentiation by cerebral thrombosis was evaluated in light
      of climatic factors.

PMID- 7739144
TI  - [Elderly non-hemophiliac patient with factor VIII inhibitor presenting various
      type hemorrhages].
AB  - A 81-year-old man who had been healthy without any history of abnormal bleeding,
      developed ecchymosis and hematuria in November, 1992 and was hospitalized in
      December, 1992. On admission, he developed widespread ecchymosis in his trunk and
      extremities, and subsequently ecchymosis of his cheek and neck, and also oral and
      pharyngeal hematoma. The laboratory data were as follows: whole blood clotting
      time, > 20 minutes; activated partial thromboplastin time (APTT), 108.6 seconds;
      Factor VIII activity, 4%. The level of Factor VIII inhibitor was high, 65.0
      Bethesda Unit/ml. This inhibitor was a IgG type immunoglobulin, which had both
      kappa and lambda light chain. His serological and blood biochemical data of the
      blood were normal, and tests for autoantibodies were negative. The patient was
      treated with plasma exchange therapy, Prednisolone (PSL), Cyclophosphamide and
      Factor VIII concentrate. The hemorrhagic symptoms were improved, the inhibitor
      disappeared and the activity of Factor VIII returned to normal after one month.
      Follow-up was continued in the outpatient clinic for 5 months. After the dose of
      PSL was decreased, he developed bloody sputum and hematuria, and was readmitted
      in August, 1994. Factor VIII activity was 21% and the titer of Factor VIII
      inhibitor was 3.0 BU/ml. The hemorrhagic symptoms disappeared soon after
      increasing the dose of PSL, and the Factor VIII activity was normalized and the
      inhibitor could not be detected. These treatments appeared to offer effective
      control on severe hemorrhage in a patient with Factor VIII inhibitor.

PMID- 7739145
TI  - [A pharmacological study of levodopa solution therapy for a patient with
      Parkinson's disease with motor fluctuations].

PMID- 7739146
TI  - [Depression in the elderly].
AB  - Depression in the elderly is characterized by agitated depression, chronic
      course, high risk of suicide, and masked depression-like states in which somatic
      symptoms are predominant. In the treatment of the elderly with depression,
      nontricyclic antidepressants are beneficial because of their few side effects. In
      addition to pharmacotherapy, psychotherapy is indispensable. Psychotherapy should
      be given frequently even though the time of each interview may be limited. The
      therapeutic efforts should be directed to coordinate the relationships among
      family members and advise the patients to take some role in their society,
      because distorted relationships among family members and the loss of roles are
      closely related to the development of depression.

PMID- 7739147
TI  - Cure with cisplatin (II) or murine malaria infection and in vitro inhibition of a
      chloroquine-resistant Plasmodium falciparum isolate.
AB  - Antiplasmodium properties of cisplatin [cis-platinum (II) diamine dichloride], a
      neoplastic drug, have been assessed in in vivo and in vitro model systems of
      malarial parasite. A well-tolerated dose of 6 mg/kg body weight of the compound
      cured the mice infected with Plasmodium berghei and the amount of cisplatin
      required for in vitro inhibition (IC50) of a chloroquine-resistant Plasmodium
      falciparum isolate was smaller than either chloroquine or quinine. The minimum
      inhibitory concentration (MIC) needed to prevent the in vitro multiplication of
      asexual blood parasites was 30 ng/ml. Late ring and trophozoite stages of the
      erythrocytic cycle were the most susceptible, whereas schizont and early ring
      stages were the least sensitive to the toxic effect of cisplatin. Multiple
      smaller doses were more effective in curing malaria in mice than a single large
      dose. In a few of the mice treated with a single intraperitoneal large dose of 6
      mg/kg body weight, there was a delay in appearance of parasitemia but most of
      them recovered completely but slowly. This compound exerts its toxicity mainly by
      randomly damaging and cross-linking DNA strands as shown by Southern
      hybridization with a synthetic oligonucleotide probe, which is a repeat sequence
      in the falciparum genome. The report clearly demonstrates the antimalarial
      potentials of this compound and suggests a closer evaluation of this and other
      related compounds, specially in combination with antimalarial drugs to probe
      their synergistic properties.

PMID- 7739148
TI  - Potential use of specific human and chicken antibodies for detection of
      Hanganutziu-Deicher antigen(s) in sera of cancer patients.
AB  - A human Hanganutziu-Deicher (HD) antibody and a chicken anti-N
      glycolyneuroaminyllactosylceramide (HD3) antibody were compared in their reaction
      against HD antigen-active ganglioside (HD3) and a glycoprotein (GP) by
      radioimmunoassay (RIA). The human antibody had a 50 times higher reactivity with
      the glycoprotein, while the chicken antibody reacted equally with both antigens.
      Both antibodies had a higher reactivities with HD antigen(s) in sera of five of
      eight lung cancer patients than 54 normal human sera. Since four of the above
      five sera had no abnormal titers to GP, it was concluded that their immunological
      status was antigen excess. The chicken antibody may be useful in follow-up
      studies of cancer patients to correlate the expression of HD antigen in tissues
      and sera with the elevation of HD antibodies, offering alternative methods of
      clinical prognosis of tumor growth and/or metastases. The human HD antibody may
      also be useful for the detection of HD antigens of glycoprotein nature.

PMID- 7739149
TI  - Production of a factor inhibiting tumor-cell migration in patients with gastric
      and breast cancer.
AB  - Production of a factor with a biological activity to inhibit the in vitro tumor
      cell migration (TCM) from peripheral blood E rosette-forming cells (ERFC), CD4+
      and CD8+ T cells in patients with gastric and breast carcinoma was investigated.
      The cells were stimulated for 2 or 24 hr with allogeneic gastric or breast cancer
      extracts in samples of cell suspensions. A microculture system at an initial cell
      concentration from 2,500 cells to 1 cell per well was used. Feeder cells, PHA, IL
      2-containing supernatant and cancer extract were added to each well. Ehrlich
      ascites tumor cells were employed in the migration-inhibition assay. ERFC and
      CD4+ T cells produced in the culture supernatants a factor inhibiting TCM, when
      these cells were stimulated with cancer extracts, but not with extracts of benign
      tissue. Stimulated CD8+ T cells did not produce such a factor. The production of
      the factor inhibiting TCM in the microculture system was also significantly
      correlated with the type of cells in the wells, particularly with ERFC and CD4+ T
      cells, but not with CD8+ T cells (r = 0.94, p < 0.001). It could be suggested
      that this factor probably took part in in vivo blockading the migration of tumor
      cells in small cancer foci.

PMID- 7739150
TI  - Growth inhibition of herpes simplex virus-1 in the cells expressing abundant 2.0
      kilobase latency-associated transcripts.
AB  - To elucidate the function of the latency-associated transcript (LAT) of herpes
      simplex virus type 1 (HSV-1) in productive infection and latency, we established
      a cell line stably expressing LAT (V24 cells). V24 cells expressed 2.0-kilobase
      RNA that corresponds to the major species of LAT in mouse and human sensory
      ganglia. When the cells were infected with HSV-1 at a low multiplicity of
      infection, the amount of the progeny virus was much smaller in V24 cells than in
      a control cell line not expressing LAT. Inefficient growth of HSV-1 in V24 cells
      was also observed when viral replication was initiated by transfection with viral
      DNA.

PMID- 7739151
TI  - [A study on thallium-201 SPECT in brain metastases of lung cancer: with special
      reference to tumor size and tumor to normal brain thallium uptake ratio].
AB  - Thallium-201 brain SPECT was performed on 20 patients with brain metastases of
      lung cancer using a three-head rotating gamma camera and the effect of tumor size
      on tumor detectability and tumor to normal brain thallium uptake ratio (T/N
      ratio) was studied. Among 71 metastatic lesions, only 9 (22.5%) of 40 lesions of
      13 mm diameter or below and 31 (100%) of 31 lesions of 14 mm diameter or above
      could be detected in this study. There was a significant correlation between T/N
      ratio and tumor size (r = 0.75, p < 0.001). The greater the metastatic lesion,
      the higher the T/N ratio. Even among the tumors in a single patient with multiple
      brain metastases, there was a significant linear correlation between tumor size
      and T/N ratio (r = 0.96, p < 0.01). In this patient, T/N ratio varied by the
      tumor size and these differences in T/N ratios were thought to be based on the
      partial volume effect. However, T/N.d which was a parameter corrected by tumor
      diameter (d) showed a constant value regardless of tumor size. The present
      results showed that T/N ratio, which was usually believed to quantitate the
      malignancy grade of brain tumor, was affected by tumor size and that more
      accurate parameter could be obtained by the correction of T/N ratio by tumor
      size.

PMID- 7739152
TI  - [Serial change of 123I-BMIPP SPECT imaging during recovery from stunned
      myocardium after acute myocardial infarction--correlation with 201Tl and two
      dimensional echocardiography].
AB  - Using 123I-beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP), we
      investigated changes in myocardial fatty acid metabolism at recovery from stunned
      myocardium after acute myocardial infarction (AMI), correlation with recovery of
      regional wall motion and thallium-201 (201Tl) distribution in particular. The
      subjects were 15 patients who underwent successful reperfusion therapy after the
      first onset of AMI. None of the patients had multi-vessel disease or ischemic
      episode during their clinical course. Patients underwent 123I-BMIPP scintigraphy,
      201Tl scintigraphy and two-dimensional echocardiography during the acute and
      chronic phases. Then, we compared regional wall motion with distribution of 123I
      BMIPP and 201Tl. Regional wall motion and SPECT were evaluated by the established
      16 segment model. In patients, showing serial improvement in regional wall
      motion, there was 80.0% (8/10) showed normal 201Tl distribution during the acute
      phase or normalized during the chronic phase. However, distribution of 123I-BMIPP
      normalized only in 10.0% (1/10) of this group. In examination of each segment
      that showed serial improvement in regional wall motion, 92.3% (24/26) of these
      segments showed normal distribution of 201Tl during the acute phase or normalized
      distribution during chronic phase, despite distribution of 123I-BMIPP improved in
      only 3.8% (1/26) of these segments. These indicate that, in the process of
      recovery from myocardial stunning after AMI, abnormal distribution of 123I-BMIPP
      continued longer than abnormal distribution of 201Tl.

PMID- 7739153
TI  - [A fundamental study of 99mTc-HMPAO double injection method and clinical
      application to stress scintigraphy in orthostatic hypotension].
AB  - Double injection method using brain perfusion 99mTc-HMPAO SPECT is popular one
      for evaluating stress scintigraphy. For appropriate evaluation of this method 555
      MBq (15 mCi) of 99mTc-HMPAO was injected twice in sequence at the resting state.
      The first and second SPECT images were obtained 5 min after each injection.
      Twenty-five ROIs of 8 x 8 pixels were placed on in various regions of the first
      images, and calculate each counts (C1). Then the counts of the same region of the
      second scan were calculated (C2). One hundred and fifty ROIs/6 patients were
      examined. We derived the linear relationship as C2 = 1.66 x C1 + 106 (r = 0.97),
      where C1 and C2 represents counts of the first scan, and second scan,
      respectively. This results suggests that the counts of the second scan is derived
      from the counts of the first scan without second scanning if they are obtained in
      the same condition. When we applied this method to stress scintigraphy, it may be
      useful for evaluating the regional brain perfusion changes before and after
      loading instead of using subtraction technique.

PMID- 7739154
TI  - [Thyroid hormones and thyroid-stimulating hormone in patients with chronic heart
      failure--relationship between primary hypothyroidism with iodine organification
      defect and chronic heart failure].
AB  - Serum concentrations of triiodothyronine (T3), thyroxine (T4) and thyroid
      stimulating hormone (TSH) were measured in 127 patients with chronic heart
      failure (CHF) (left ventricular ejection fraction; 40% < or = and NYHA; III-IV),
      and 1,079 patients without CHF (non-CHF) (left ventricular ejection fraction; 40%
      < or = and NYHA; I-II). Serum-T3, T4 and free-T4 were significantly decreased in
      patients with CHF. The prevalence of slight increase of serum TSH (5 < or = TSH <
      15 microU/ml) were 20.5% in CHF and 4.08% in non-CHF. There was a statistically
      significant difference in the prevalence of slight increase of TSH (p < 0.01). In
      the patients with slight increase of serum TSH, the 123I-thyroid scintigraphy and
      perchlorate test were performed 12 patients with CHF and 19 patients with non
      CHF. The incidences of iodine organification defect were 33.3% in CHF and 5.26%
      in non-CHF. There was a statistically significant difference in the incidence of
      iodine organification defect (p < 0.05). The histologic examination of thyroid
      biopsy specimen obtained 12 patients with CHF and primary hypothyroidism, these
      revealed only non-specific mild atrophic changes. Follicular damage and
      lymphocyte-infiltration were not evident. These findings suggest that the primary
      hypothyroidism were frequently complicated in CHF and associated with iodine
      organification defect by reduction of thyroid-peroxidase activity or decrease of
      hydrogen peroxidase. We conclude that the primary hypothyroidism with iodine
      organification defect was probably developed as a result of CHF.

PMID- 7739155
TI  - [The relationship between the cerebral blood flow, oxygen consumption and glucose
      metabolism in primary degenerative dementia].
AB  - The CBF, CMRO2 and CMRGlu were measured in patients with primary degenerative
      dementia including 5 patients with dementia of Alzheimer's type and 4 patients
      with Pick's disease, and then the correlation between the cerebral blood flow and
      energy metabolism was evaluated. The control subjects consisted of 5 age-matched
      normal volunteers. The CBF, CMRO2 and CMRGlu decreased in the bilateral frontal,
      temporal and parietal regions in the patients with Alzheimer's dementia, while
      they decreased in the bilateral frontal and temporal regions in the patients with
      Pick's disease. Both the CBF and CMRO2 were closely correlated with each other.
      However, the CMRGlu was more severely impaired than the CBF or CMRO2 in both
      pathological conditions. These results suggested that CMRGlu began to decrease
      before the reduction of the aerobic metabolism and thus measuring the CMRGlu is
      considered to be the most sensitive method for detecting abnormal regions in
      primary degenerative dementia.

PMID- 7739156
TI  - [Quantitation of regional cerebral blood flow using 123I-IMP from a single SPECT
      scan and a single blood sampling--analysis on statistical error source and
      optimal scan time].
AB  - Recently, a method has been proposed to measure quantitative regional cerebral
      blood flow (rCBF) in man using N-isopropyl-p-[123I]-iodoamphetamine (IMP) and
      single photon emission tomography (SPECT). In this method (IMP-ARG method), a
      functional map of rCBF was calculated from a single SPECT scan data set, in which
      effects of the clearance of IMP from the brain was taken into account by
      employing the 2 compartment model. To avoid the procedures of frequent and/or
      continuous sampling of the arterial blood that was required in determination of
      the input function, use of a standard input function and calibrating it by one
      blood sampling were validated. The present study was intended to investigate the
      sensitivity to various sources of errors in the IMP-ARG method such as (1)
      effects of individual difference of the arterial input function, (2) effects of
      ambiguity of the regional distribution volume (Vd) of IMP, and (3) effects of
      inaccuracy of the SPECT measurement. It was shown in the present simulation study
      that errors in the calculated rCBF values were dependent on the SPECT mid-scan
      time (MST), and that the minimum error corresponded to the MST of approximately
      30 min after the IMP infusion. With this optimal MST, errors in rCBF due to the
      individual difference of the input function was approximately 10%, and the errors
      due to the ambiguity of the Vd were approximately 8%. The total accuracy of the
      calculated rCBF in the IMP-ARG method was, therefore, estimated as approximately
      13%. Although a relatively large error was expected at a high rCBF area, this
      study strongly suggested the IMP-ARG method being useful and accurate for
      providing the quantitative rCBF map for a clinical use.

PMID- 7739157
TI  - [High incidence of false positive results of thallium-201 myocardial stress
      scintigraphy for the evaluation of artery bypass graft patency after CABG].
AB  - We have often experienced false positive results of the stress Thallium-201
      myocardial scintigraphy (TL) for the evaluation of artery bypass graft patency
      after coronary artery bypass surgery (CABG). The purpose of this study is to
      clarify the frequency and the clinical significance of this findings. Sixty-two
      patients undergoing coronary angiography (CAG) after CABG were studied. These
      patients had undergone at total of 156 bypasses (artery grafts 108, saphenous
      vein grafts 48, mean bypass grafts number 2.65/cases), and the mean period from
      CABG to TL was 41.6 +/- 34 days. The territories of stress induced ischemia were
      divided into 3 territories; left anterior descending (LAD), right coronary artery
      (RCA), and left circumflex (LCX) territories. Patency of the bypass grafts was
      estimated on the absence of transient perfusion defect (TPD) on TL images. The
      incidence of false positive results was higher in Dipyridamole TL (38%) than in
      Exercise TL (18%) and higher in LAD territories (38%) than in RCA (11%) and LCX
      (13%) territories. All false positive cases showed no evidence of chest pain and
      significant ST-T change during stress TL test. High incidence of false positive
      results of stress TL test was observed for the evaluation of artery bypass graft
      patency after CABG.

PMID- 7739158
TI  - [Relationship between 123I-BMIPP imaging and cardiac function in acute myocardial
      infarction].
AB  - We evaluated the relationship between free fatty acid metabolism using 123I beta
      methyl-iodophenyl pentadecanoic acid (BMIPP) and cardiac function in acute
      myocardial infarction. Twenty-five patients were examined with 123I-BMIPP and
      201Tl dual SPECT. The 123I-BMIPP images were compared with the 201Tl images and
      the left ventricular wall motions. The 123I-BMIPP images showed a larger uptake
      defect than the 201Tl images. This was marked in the patients after
      revascularization therapy. The uptake decrease of 123I-BMIPP was in good
      agreement with the decrease in regional wall motion. The incidence of accordance
      was 79% of the wall segments. The correlation between 123I-BMIPP defect size and
      ejection fraction was higher (r = -0.54) than that of 201Tl (r = -0.44).
      Subtraction of ejection fractions four weeks and soon after infarction correlated
      well with the subtraction of 123I-BMIPP and 201Tl defect sizes (r = 0.55). In
      conclusion, 123I-BMIPP is more closely related to wall motion, than 201Tl and
      might be valuable in predicting the functional improvement of acute myocardial
      infarction.

PMID- 7739159
TI  - [SPECT evaluation of cerebral perfusion reserve in patients with occlusive
      cerebrovascular diseases: evaluation with acetazolamide test and crossed
      cerebellar diaschisis].
AB  - In 53 patients with chronic occlusive cerebrovascular diseases, we evaluated
      cerebral perfusion reserve. Cerebral perfusion reserve was evaluated by the
      change in cerebral blood flow (CBF) at rest and the CBF after acetazolamide
      (Diamox) as measured by the 133Xe gas inhalation SPECT method. Crossed cerebellar
      diaschisis (CCD) was evaluated semiquantitatively by the count ratio of the
      cerebellar cortex using 99mTc-HMPAO SPECT. Thirty-two (49%) of the 65 affected
      lesions in 53 patients had shown a decreased response to Diamox. In the cases of
      decreased response to Diamox, the response improved significantly after surgery.
      However, CBF did not improve as much as the response. In the 40 nonaffected
      sides, 21 (53%) showed decreased CBF at rest but good response to Diamox. At
      rest, no difference of the CBF ratio (affected/contralateral nonaffected cerebral
      cortex) was observed between the patients with CCD (6 pts) and those without CCD
      (8 pts). After Diamox, however, the CBF ratio of the patients with CCD was
      significantly higher than that without CCD. The change of the CBF ratio before
      and after Diamox correlated significantly with the degree of CCD (r = -0.794, p <
      0.01). Diamox was useful for evaluating the cerebral perfusion reserve to
      indicate surgery in patients with chronic cerebrovascular diseases. Perhaps CCD
      could be a useful index in the differentiation of the decreased CBF caused by
      reduced perfusion pressure from that caused by reduced metabolic demand because
      CCD had a close relationship with the cerebral perfusion reserve.

PMID- 7739160
TI  - [Two cases of dilated cardiomyopathy with the relationship between the effect of
      beta-blocker therapy and the changes of myocardial clearance of 123I
      metaiodobenzylguanidine].
AB  - Two cases diagnosed dilated cardiomyopathy received beta-blocker therapy, and
      underwent 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy before and
      after the treatment. In case 1, symptoms and cardiac function were improved in 1
      month and 4 months after the treatment (LVEF increased from 19% to 32% and 40%),
      and myocardial clearance of MIBG decreased from 50% to 27% and 29%. In case 2,
      both symptoms and cardiac function were not improved in 1 month and 3 months
      after the treatment (LVEF was changed from 11% to 10% and 13%), and myocardial
      clearance was not significantly different between before (50%) and after (1
      month: 46%, 3 months: 50%) the treatment. It was indicated that myocardial
      clearance of MIBG might depend on the extent of the improvement of cardiac
      function and symptoms, and might reflect the effects of beta-blocker therapy.

PMID- 7739161
TI  - [Artificial defect on myocardial SPECT image due to extra-cardiac MIBI
      accumulation].
AB  - If 99mTc-methoxy isobutylisonitrile (MIBI) myocardial scintigraphy was performed
      on the rest-stress protocol, MIBI accumulated in extra-cardiac area, gallbladder
      or liver, on rest image significantly. The purpose of this study was to evaluate
      whether extra-cardiac MIBI accumulation influences the quality of myocardial
      images. Rest-stress MIBI myocardial scintigraphy was performed in 90 patients.
      Fifteen patients showed defects on rest image in spite of normal findings on
      stress image. Before and after removing the area of extra-cardiac MIBI
      accumulation on projection images, SPECT was reconstructed in the 15 patients.
      Perfusion defect on rest image improved in 66% of patients (10/15) and 37% of
      total segments (33/89) by removing the area of extra-cardiac MIBI accumulation.
      Furthermore, it was 21% (4/19), 38% (11/29), 43% (16/37) and 50% (2/4) in
      anterior, septum, posterior and lateral segments respectively. Significant MIBI
      extra-cardiac accumulation, especially in the gallbladder, is one of the causes
      of artificial defects on rest image. Thus, reconstruction of SPECT after removing
      area of MIBI extra-cardiac accumulation will be an appropriate method to improve
      the quality of MIBI images.

PMID- 7739162
TI  - [Evaluation of the residual functional reserve and the early regeneration after
      the hepatic resection using asialoglycoprotein receptor imaging agent].
AB  - 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) is a newly developed liver
      imaging ligand which specifically binds to asialoglycoprotein receptor on the
      hepatic cell surface. We investigated whether 99mTc-GSA scintigraphy was able to
      be used as indexes for the residual functional reserve and the early regeneration
      of the hepatocyte after the hepatic resection. Four patients with metastatic
      liver cancer, 3 patients with hepatocellular carcinoma, and 1 patient with
      cholangiocellular carcinoma were studied. Basically, each patient was examined 4
      times (before, 3, 10, 20 days after the operation). Immediately after i.v.
      injection of 185 MBq (3 mg) of 99mTc-GSA, serial images and dynamic data were
      obtained. Serial changes of HH15, as an index of blood clearance of the tracer
      calculated from the uptake ratio of heart at 15 minutes to that at 3 minutes, and
      LHL15, as an index of hepatic accumulation calculated from the uptake ratio of
      liver to liver plus heart at 15 minutes after the injection were analyzed before
      and after hepatectomy. Three out of 4 lobectomy patients which showed increased
      HH15, and decreased LHL15 as compared with the preoperative data were considered
      to be decreased residual hepatic functional reserve. The remaining one lobectomy
      patient showed increased HH15, but increased LHL15 inversely. One patient of two
      partial resections of hepatocellular carcinoma with liver cirrhosis demonstrated
      transiently decreased HH15, and increased LHL15. Two patients with metastatic
      liver cancer (one partial resection, six partial resections) showed decreased
      HH15, and increased LHL15. Postoperatively increased hepatic accumulation was
      presumed to be increased functioning hepatocyte or transiently increased
      asialoglycoprotein receptor on the cell surface by up-regulation. 99mTc-GSA
      scintigraphy might be helpful for non-invasive method to detect the residual
      functional reserve and the early regeneration of the hepatocyte after the hepatic
      resection.

PMID- 7739163
TI  - [Primary lung cancer in young patients].
AB  - We studied the clinical characteristics and prognosis of patients, 40 years old
      or younger, in whom primary lung cancer was diagnosed and treated at National
      Nishigunma Hospital between 1982 and 1993, and compared them with those of 978
      patients more than 40 years old. Younger patients numbered 30 (3.0%). Females
      accounted for 16 of the 30 cases (53.3%), a proportion higher than the female:
      male ratio for the older patients (27.8%). There were more smokers among the
      older patients (72.8%) than among the younger patients (53.3%) (p < 0.01).
      Adenocarcinoma was significantly more common (19/30, 63.3% vs 43.8%, p < 0.05)
      and squamous cell carcinoma was less common (3.30, 10.0% vs 34.3%, p < 0.05) in
      the younger patients than in the older patients. Median survival time in younger
      patients was 30.0 months, and in older patients it was 14.6 months, but we found
      no significant difference in survival between younger and older patients. In the
      younger group, all the cases of stage I or II disease were discovered during mass
      screening.

PMID- 7739164
TI  - [Evaluation of the pulmonary vascular bed by digital subtraction angiography].
AB  - We studied the usefulness of digital subtraction angiography for evaluating the
      pulmonary capillary bed. Four individuals underwent the procedure. One was a
      healthy volunteer and the others were patients with chronic pulmonary emphysema.
      During catheterization, an 8 F balloon catheter was manipulated into the right
      pulmonary artery. A total of 20 ml of contrast material was injected at a rate of
      10 ml/sec at full inspiration. In the normal subject, the capillary bed filled
      homogeneously and no defect was seen. In the patients, the pulmonary artery was
      nearly normal, but severe defects were observed in the pulmonary capillaries.
      Contrast resolvability was greater with digital subtraction pulmonary angiography
      than with pulmonary perfusion scintigraphy or pulmonary arteriography. This
      technique makes possible the visual evaluation of the pulmonary capillary bed.

PMID- 7739165
TI  - [Utility of polymerase chain reaction for diagnosis of tuberculous pleural
      effusion].
AB  - Polymerase chain reaction (PCR) assay to detect Mycobacterium tuberculosis was
      done on 14 pleural fluid samples. Eight samples were from patients with pleural
      effusions suspected to be tuberculous that were smear-negative and culture
      negative for acid-fast bacilli, and six samples were from patients with malignant
      effusions. The DNA extracted from samples was amplified with two different pairs
      of primers of the 123-bp and the 383-bp target DNAs of the bacilli. Mycobacterial
      DNA was detected in all eight samples of effusions suspected to be tuberculous,
      but it was not detected in any malignant effusions. We conclude that PCR assay
      may be useful for the rapid diagnosis of tuberculous pleural effusions that are
      smear-negative and culture-negative.

PMID- 7739166
TI  - [A clinical study on superior sulcus tumors].
AB  - Twenty nine patients with superior sulcus tumors (26 men and 3 women) were
      studied. The incidence was 2.1% of 1350 patients with lung cancer. The mean age
      was 66.2 years, and 27 patients (93.1%) had a history of smoking (B.I. = 1193.7).
      There were 10 adenocarcinomas, 9 squamous cell carcinomas, 5 large cell
      carcinomas 4 small cell carcinomas, and 1 that could not be classified. Fifteen
      patients (51.7%) had Stage IV disease on admission. Eight patients (27.6%)
      presented with symptoms outside the chest. Pancoast syndrome was recognized in 9
      patients (31.0%). In 15 patients (51.7%) the diagnosis was made by transbronchial
      biopsy and in 10 patients (34.5%) it was made by echoguided needle biopsy. Tumors
      were located in a posterior lesion in 13 patients (44.8%). Twenty patients were
      given radiation therapy. Clinical staging, irradiation, and surgical treatment
      were related to the length of survival. The median survival time was 7 months.

PMID- 7739167
TI  - [Vasoactive intestinal peptide (VIP)-induced pulmonary vasodilation mediated by
      EDRF/NO in isolated perfused rat lungs].
AB  - We studied the effects of Vasoactive Intestinal Peptide (VIP) on the pulmonary
      circulation in isolated perfused rat lungs. VIP caused pulmonary vasodilation in
      a dose-dependent manner. This effect was inhibited by pretreatment with L-N omega
      nitro-arginine (L-NNA), a competitive inhibitor of endothelium-derived relaxing
      factor (EDRF/NO), but not by meclofenamate, a cyclooxygenase inhibitor. Addition
      of L-arginine, a substrate of EDRF/NO, after treatment with L-NNA reversed VIP
      induced pulmonary vasodilation. These results indicate that VIP causes pulmonary
      vasodilation, and they suggest a role for EDRF/NO in VIP-induced pulmonary
      vasodilation in isolated rat lungs.

PMID- 7739168
TI  - [Endothelial metaplasia of the alveolar capillaries in experimental silicosis of
      rats].
AB  - We studied, by immunohistochemical and ultrastructural observations, the basic
      mechanism of interstitial fibrosis and endothelial metaplasia of alveolar
      capillaries in the lungs of Sprague-Dawley rats that received a single
      intratracheal infusion of silica particles. Immediately after silica
      administration, alveolar capillaries collapsed and their endothelial cells became
      necrotic over wide ranges. Alveolar myofibroblasts migrated into luminal
      silicaladen granulomas through defects in the alveolar linings. They proliferated
      and produced collagenous matrices that were incorporated into adjacent walls by
      coverage of regenerating epithelial cells. By day 4, endothelial cells of
      peribronchiolar small vessels had become positive for proliferating cell nuclear
      antigen. These endothelial cells apparently migrated along alveolar capillary
      tubes to replace injured endothelial cells through the processes of
      interdigitation of their cytoplasms. After one month, these alveolar endothelial
      cells, which were originally negative for factor VIII-related antigen (F-VIII)
      had become positive, especially in those segments in fibrotic scars. These
      endothelial cells developed numerous Weibel-Palade bodies containing F-VIII. Some
      endothelial cells formed specific ultrastructural fenestrations, which are unique
      to capillary endothelial cells that originated from bronchial arteries. The
      mechanism of endothelial metaplasia might consist of the following processes in
      endothelial cells that originated from broncho-pulmonary anastomoses:
      proliferation, migration, replacement, and differentiation of endothelial cells
      of bronchial arteries in the chronic fibrotic stages.

PMID- 7739169
TI  - [Restricted T cell receptor V beta gene expression in bronchoalveolar lavage
      lymphocytes of patients with sarcoidosis].
AB  - T lymphocytes in bronchoalveolar lavage (BAL) fluid from patients with
      sarcoidosis are activated. They are thought to recognize as yet unknown antigens
      and to play an important role in the pathogenesis of the disease. We studied the
      use of the T cell receptor V beta gene of lymphocytes obtained by BAL and
      lymphocytes obtained from peripheral blood of 11 patients with sarcoidosis and 9
      normal controls, using the reverse transcriptase-polymerase chain reaction. As
      compared to the normal controls, V beta 2 and V beta 6 genes were predominantly
      expressed (> 15% of the sum of all V beta transcripts) on lymphocytes obtained
      from BAL fluid in 4 and 7 of 11 patients with sarcoidosis, respectively, but no
      specific V beta gene was predominantly expressed on lymphocytes obtained from
      peripheral blood. These results imply that those lymphocytes that are obtained
      from BAL fluid and that express V beta 2 and V beta 6 genes are involved in the
      pathogenesis of sarcoidosis.

PMID- 7739170
TI  - [Radiological and pathological analysis of the distribution of centrilobular
      emphysema in the transverse plane of the lung].
AB  - The distribution of centrilobular emphysematous lesions in the transverse plane
      was studied with high-resolution CT (HRCT) images of inflated and fixed lungs
      obtained from 49 patients with centrilobular emphysema (CLE). The transaxial
      distribution of low attenuation areas (LAA) was assessed quantitatively on HRCT
      images obtained from 21 patients. LAA in the outer layer accounted for a
      significantly lower ratio of the lung parenchyma than did those in the inner
      layer. Macroscopic analysis of 31 lobes obtained from 28 patients with CLE was
      done by point counting. The inner layer had many more LAA than the outer layer.
      Bronchiolar lesions were examined under the microscope for their relation to the
      observed variations in distribution in CLE. No significant differences were found
      in the bronchiolar lesions between the inner and outer layers. These data show a
      characteristic distribution pattern of CLE in the transverse plane. They also
      suggest that the disparity in distribution of LAA between the inner and outer
      layers is not influenced by the grade of bronchiolar pathological lesions.

PMID- 7739171
TI  - [Efficacy and assessment of patient education as related to morbidity from
      asthma].
AB  - Asthmatic patients are sometimes ignorant of their treatment and of the
      pathophysiology of their disease. In such patients, anxiety about the disease may
      worsen their condition. We studied the effects of an educational program for
      bronchial asthma. In 45 patients, the Severity of Asthma Scores before and after
      the program were measured. Sixty percent of the patients were assessed as
      "improved". On self-administered questionnaires concerned with asthma, most of
      the patients indicated that the program significantly improved their condition,
      reduced apprehension about the disease, and increased their trust in the
      hospital. In 24 patients, three psychological tests were done. Results of the
      comprehensive asthma inventory indicated that the program was useful for
      dependent and self-disciplined patients, but was not useful for resigned and
      depressed patients. The Y-G test showed that most of the patients who were helped
      by the program were introverted. Results of the Edwards Personal Preference
      Schedule revealed a difference in desire between the group that benefitted from
      the program and the group that did not. These results suggest that each group had
      a certain inclination toward psychogenic symptoms. Therefore, psychological tests
      are useful for predicting the effects of education. In conclusion, educational
      programs for patients with bronchial asthma may affect morbidity from asthma.
      Possible mechanisms include relief of anxiety about the disease and improvement
      in the patient's compliance with prescribed therapy.

PMID- 7739172
TI  - [Bone mineral content in patients with bronchial asthma].
AB  - To study the factors related to bone mineral content (BMC) in patients with
      bronchial asthma (BA), we measured BMC of the whole body, bone mineral density
      (BMD) in the second, third, and fourth lumbar vertebrae (by dual energy X-ray
      absorptiometry, DXA XR-26, Norland), and pulmonary function in patients with BA.
      Subjects were 103 patients with BA and 194 age-matched normal controls. There was
      no significant difference in BMC or BMD between patients with BA and controls. In
      patients with BA, there was no significant difference in BMC or BMD between those
      who were taking steroids and those who were not. BMC and BMD were significantly
      correlated with age, body weight, VC, %VC, and FEV1, but not with the duration of
      steroid administration or the total steroid dose administered. These results
      suggest that patients with BA have normal BMC and that steroid administration
      does not affect bone mineral loss in such patients.

PMID- 7739173
TI  - [Effects of temperature and humidity on the stability of nitric oxide, and
      efficacy of soda lime as a selective absorber of nitrogen dioxide].
AB  - Although inhaled nitric oxide (NO) has attracted attention as a pulmonary
      vasodilator, little heed has been given to its potential toxicity. Nitric oxide
      is known to be rapidly oxidized to nitrogen dioxide (NO2), which may damage
      pulmonary tissue. We examined the effects of temperature and humidity on the
      production of NO2 from NO. We also evaluated the amount of NO2 absorbed by soda
      lime, which is usually placed in the inspiratory line. For this purpose, we
      measured changes over time in the concentrations of NO and NO2 in mixtures that
      included NO, oxygen, and nitrogen in various concentrations, and at different
      temperatures and humidities. We confirmed that the formation of NO2 from NO
      follows the equation: -d[NO]/dt = 2 k[NO]2 [O2], where k is the rate constant. We
      found that k was significantly smaller at 37 degrees C than at 25 degrees C but
      was not influenced by humidity (0%, 40% or 90%). Although soda lime was very
      effective in absorbing NO2 from the inspiratory line, NO was simultaneously
      absorbed at the same molar ratio when the two gases existed together in the line.
      We thus conclude that inhalation of NO at 37 degrees C is more desirable than
      inhalation at room temperature, to suppress the production of NO2. When soda lime
      is used in the inspiratory line, attention should be paid to the reduction in the
      concentration of NO in the line.

PMID- 7739174
TI  - [Two cases of acute massive pulmonary embolism diagnosed by pulmonary angiography
      with Swan-Ganz catheter].
AB  - We report two cases of acute massive pulmonary embolism diagnosed at the bedside
      by pulmonary angiography with Swan-Ganz catheter. In both cases the patients
      (women 48 and 49 years old) went into shock after surgery. Pulmonary angiography
      with Swan-Ganz catheter was done at the bedside to confirm the diagnosis. In both
      cases this revealed filling defects. Hemodynamics improved after-thrombolytic
      therapy. In general, pulmonary embolism can be definitively diagnosed by lung
      perfusion scan or pulmonary angiography. Pulmonary angiography with a Swan-Ganz
      catheter is useful in hospitals without complicated instruments, but is indicated
      only for unmovable and unstable patients with hemodynamic problems.

PMID- 7739175
TI  - [Systemic necrotizing vasculitis with pulmonary hemorrhage and gastrointestinal
      bleeding].
AB  - A 61-year-old man was admitted to our hospital with pain and weakness in both
      lower legs. Eosinophil count was abnormally high (6800/mm3). Chest X-ray film
      revealed multiple infiltrates in both lung fields. A specimen obtained by
      transbronchial lung biopsy demonstrated pulmonary hemorrhage. Vasculitis syndrome
      was suspected and 1 g per day of methylprednisolone was administered for 3 days.
      Pulmonary infiltrates quickly disappeared, but 2 weeks later massive intestinal
      hemorrhage occurred. Emergency ilectomy was done, but the patient died of
      bleeding from other intestinal lesions. Microscopic examination of the resected
      ileum revealed mucosal ulceration and necrotizing vasculitis in small arteries.
      This case is important in that vascular occlusion and ischemia progressed soon
      after vascular inflammation was relieved by administration of corticosteroid
      hormone.

PMID- 7739176
TI  - [Obstructive sleep apnea syndrome associated with superior vena cava syndrome].
AB  - A 43-year-old man was admitted suffering from dyspnea on exertion and edema of
      the neck and face. Chest X-ray film and CT scan revealed a mediastinal tumor and
      a right pleural effusion. A biopsy of the tumor revealed poorly differentiated
      carcinoma. Severe snoring at night and excessive daytime sleepiness were noticed
      after admission. Nocturnal oxygen desaturation was documented with a pulse
      oximeter, and obstructive sleep apnea syndrome was diagnosed on the basis of
      results of respiratory inductive plethysmography. The severity of snoring and
      oxygen desaturation during sleep correlated well with the progression of facial
      swelling. Combination chemotherapy (carboplatin 300 mg/m2 day 1, vindesine
      sulfate 3 mg/m2 day 1 and 8) was started but no improvement was seen. An
      expandable metallic stent was inserted into the stenotic vena cava, and the
      facial swelling, snoring, and oxygen desaturation during sleep were promptly
      relieved. In this case, obstructive sleep apnea was caused by edema and vascular
      congestion in the upper airway, and by the decrease in pharyngeal inspiratory
      muscle function caused by superior vena cava syndrome.

PMID- 7739177
TI  - [Congenital protein C deficiency with pulmonary infarction].
AB  - A 45-year-old man was admitted with left chest pain and hemoptysis. Chest CT on
      admission showed multiple areas of wedge-shaped consolidation in both lung
      fields. A perfusion lung scintigram showed bilateral deficits in both lungs,
      whereas a ventilation scintigram was normal. The serum concentration and the
      functional activity of protein C were 41% and 42%, respectively. The same results
      were obtained from studies of the patient's mother and two sons, which indicated
      that this was a case of congenital protein C deficiency with pulmonary
      infarction.

PMID- 7739178
TI  - [A case of pulmonary tuberculoma with pneumoconiosis (graphite lung) that
      appeared to be lung cancer].
AB  - We report a rare case of tuberculoma with pneumoconiosis (Graphite lung). A 62
      year-old man was admitted to our hospital for diagnosis of a rapidly growing coin
      lesion in the right lung (S8). He had worked for 42 years in a foundry and given
      a diagnosis of pneumoconiosis (Graphite lung). Because transbronchial lung biopsy
      and percutaneous needle aspiration biopsy were not diagnostic, the right lower
      lobe was partially resected. Histological examination revealed the presence of
      caseous necrosis in a solitary mass. Therefore, it is important to consider
      tuberculoma in the differential diagnosis of a coin lesion in patients with
      pneumoconiosis.

PMID- 7739179
TI  - [A case of probable allergic bronchopulmonary aspergillosis due to Aspergillus
      niger].
AB  - We report a case of probable allergic bronchopulmonary aspergillosis (ABPA) due
      to Aspergillus niger. An 80-year-old woman was admitted to our hospital because
      of wheezing, expectoration of a mucous plug and atelectasis of the right lower
      lobe as seen on a chest X-ray film. The patient had eosinophilia and immediate
      wheal-and-flare skin reactivity to A. fumigatus. Serum precipitating antibodies
      against A. niger and elevated serum IgE, however, were absent. Mucus impaction
      and bronchiectasis were revealed by both bronchoscopy and CT scanning. The mucous
      plug contained A. niger, numerous eosinophils and Charcot-Leyden crystals.
      Corticosteroid therapy ameliorated the symptoms and abnormal laboratory findings.
      Therefore, this was a rare, informative case of probable ABPA due to A. niger
      associated with a normal level of serum IgE and negative precipitation antibodies
      against A. niger antigen.

PMID- 7739180
TI  - [A case of chronic necrotizing pulmonary aspergillosis in which intravenous
      infusion of amphotericin B was effective].
AB  - A 49-year-old man with a history of left upper lung lobectomy for pulmonary
      asperigilloma developed a productive cough in the middle of April 1992, and his
      chest X-ray film showed infiltration of the left S6. Treatment with several
      different antibiotics was tried, but the shadow expanded and developed a cavity
      over the following 8 months. A clinical diagnosis of chronic necrotizing
      pulmonary aspergillosis was made, based on repeated detection of Aspergillus
      fumigatus in the patient's sputum and in specimens obtained by fiberoptic
      branchoscopy and percuraneous needle biopsy. Prior lobectomy and a marked
      idiopathic decrease in ventilation and perfusion in the affected lung are risk
      factors for this disease. Slow intravenous infusion of amphotericin B eradicated
      the fungus without any side effects. Measurement of drug concentrations during
      treatment revealed that the concentration in the sputum was far higher than that
      in the serum, and was also far higher than the minimum inhibitory concentration
      for the fungus.

PMID- 7739181
TI  - [A case of pulmonary fibroma].
AB  - A 42-year-old man without symptoms was admitted to the hospital because of a well
      circumscribed mass in his left upper lung field, which was found on a routine
      chest X-ray film. CT of the chest revealed a well-defined homogeneous mass in the
      left upper lobe. Bronchial biopsy yielded material unsatisfactory for diagnosis.
      On thoracotomy a tumor, entirely within the lung parenchyma, was found to occupy
      S3. Due to its size and location left upper lobectomy was done. Histologically,
      the tumor contained interlacing bundles of spindle cells compatible with fibroma,
      with no indicators of malignancy. Intrapulmonary fibromas are rare and only one
      report could be found in the Japanese literature.

PMID- 7739182
TI  - [A case of pulmonary tuberculosis associated with triple cancer].
AB  - A 76-year-old man came to our hospital complaining of bloody sputum and anterior
      chest pain. He had undergone operations for rectal cancer six years previously
      and for gastric cancer nine months previously. His chest X-ray film showed a mass
      shadow in the left lower field and a small nodular shadow in the right middle
      field. After treatment with antibiotics and antituberculosis drugs, symptoms and
      laboratory findings improved and left mass shadow on the chest X-ray film began
      to resolve. Adenocarcinoma of the lung was diagnosed after a transbronchial lung
      biopsy from the right S3a. An operation was scheduled for two months later, but a
      new mass shadow appeared in the right lower field. Right upper lobectomy with
      mediastinal lymph node dissection and partial resection of the right S9 was done.
      The surgical specimens revealed well-differentiated adenocarcinoma from the right
      S3a and tuberculosis from the right S1, S2, and S9. A recent increase in multiple
      cancers has been noticeable, but cases of triple cancer concurrent with
      tuberculosis are rare. When chest-radiographic abnormalities unrelated to the
      original tumor occur in lung cancer patients, a second primary cancer should be
      considered. It is also important to determine if they are caused by intra-lung
      metastases or by some other condition, such as exacerbation of pulmonary
      tuberculosis.

PMID- 7739183
TI  - [A case of sarcoidosis with advanced cystic and fibrotic changes in a young
      patient].
AB  - A 29-year-old man was referred to our hospital because of exertional dyspnea and
      progressive eruption on the buttocks and the lower extremities. Chest
      roentgenograms and computed tomograms taken at that time revealed diffuse
      fibrotic changes accompanied by multiple cavities and bullae in the lungs. There
      were no signs of mediastinal or hilar lymphadenopathy. A chest roentgenogram
      taken 7 years before admission showed no abnormalities. Serum ACE and lysozyme
      levels were high: 29.9 IU/l and 14.1 micrograms/ml, respectively. 67Ga
      scintigraphy showed diffuse uptake in both lung fields. The PPD skin test was
      negative, and repeated sputum smears and cultures were negative for pyogenic
      bacteria and acid-fast bacilli. Examination of transbronchial lung biopsy and
      skin biopsy specimens confirmed the diagnosis--they showed noncaseating
      epithelioid granulomas with giant cells and a negative reaction of the stain to
      acid-fast bacilli, which are compatible with sarcoidosis. The patient was given
      30 mg/d of prednisone orally. The dyspnea and eruption were clearly alleviated,
      although there was little roentgenographic regression of cystic or fibrotic
      changes. There have been only a few reports of cystic and fibrotic changes early
      in the course of sarcoidosis. The cystic lesions in this case were probably
      secondary pulmonary cavities caused by the contracting and obstructive changes
      related to pulmonary fibrosis.

PMID- 7739184
TI  - [Malignant fibrous histiocytoma of the lung].
AB  - A 68-year-old man had a malignant fibrous histiocytoma of the lung that was found
      at autopsy. The patient was admitted to our hospital because of exertional
      dyspnea. A chest X-ray film and chest CT scan showed atelectasis in the left
      upper lobe. Examination with a fiberoptic bronchoscope revealed a necrotic mass
      in the left mainstem bronchus. Microscopic examination of a biopsy specimen
      disclosed several atypical giant cells but was not diagnostic. He underwent
      chemotherapy with CBDCA, IFM and VP-16, because a malignant tumor of the lung was
      strongly suspected. After three cycles of chemotherapy, the tumor had shrunk, as
      demonstrated on repeated bronchoscopy. The patient's condition improved
      temporarily, but he began to complain of dyspnea, and died of respiratory
      insufficiency despite radiotherapy. Postmortem examination was done. The tumor in
      the lung was mainly composed of spindle-shaped fibroblast-like cells and several
      pleomorphic giant cells with multiple nuclei, with storiform and fascicular
      patterns. Immunohistochemically, these tumor cells were shown to contain
      vimentin, alpha-1-antitrypsin, and LN-5. These findings were compatible with
      malignant fibrous histiocytoma of the lung.

PMID- 7739185
TI  - [A necrobiotic nodule indistinguishable from lung adenocarcinoma].
AB  - A 43-year-old woman was referred for examination because of an abnormal shadow on
      a chest X-ray film. She had a 12-year history of seropositive rheumatoid
      arthritis. Chest X-ray films and CT scans showed a pleurabased solitary nodule
      without a cavity. Cytological examination of a transbronchial biopsy specimen did
      not lead to a diagnosis, so thoracoscopic enucleation was performed.
      Histologically, the nodule consisted of lymphocytes and fibroblasts surrounding a
      central necrotic area, which indicated that it was a rheumatoid nodule. This
      solitary necrobiotic nodule was radiographically indistinguishable from lung
      adenocarcinoma, so histologic confirmation was necessary.

PMID- 7739187
TI  - [70th annual meeting of the Japanese Society for Tuberculosis. Nagoya City. April
      10-11, 1995. Abstracts].

PMID- 7739186
TI  - [Scimitar syndrome with diagnostic MRI findings].
AB  - A fifty-year-old woman was admitted to our hospital because of an abnormal shadow
      on a chest X-ray film. She was asymptomatic. Chest X-ray film showed a scimitar
      like vessel in the right lung, dextroposition of the heart, and hypoplasia of the
      right pulmonary artery. MRI revealed that the scimitar vein was anomalous
      pulmonary venous return from the right lung. Normal venous return from the right
      lower lobe to the left atrium was confirmed by pulmonary artery angiography. MRI
      findings have been useful in the diagnosis of scimitar syndrome.

PMID- 7739188
TI  - [Corneal reinnervation after keratomileusis in situ and keratomileusis myopica--a
      comparison].
AB  - BACKGROUND: In a retrospective study corneal sensitivity after keratomileusis in
      situ and keratomileusis myopica was measured. METHOD: 5 points on the cornea were
      measured with the Draeger aesthesiometer at 18 eyes after keratomileusis myopica
      and at 66 eyes after keratomileusis in situ. RESULTS: The ingrowth of corneal
      nerve fibres is delayed after keratomileusis myopica compared to keratomileusis
      in situ because of delayed stromal repopulation of keratocytes and disturbances
      of stromal metabolism due to toxic effects of the cryopreservation solution.

PMID- 7739189
TI  - [Comparison of the measurement values of the laser tomography scanner and optic
      nerve head analyzer. A clinical study].
AB  - INTRODUCTION: With the Laser Tomographic Scanner (LTS) and the Optic Nerve Head
      Analyzer (ONHA) a quantifying investigation of the optic disc is possible. Both
      work with different principles: The LTS receives the information about the three
      dimensional structure with 32 transversal cuts, taken with the confocal
      principle, the ONHA with simultan stereopictures, taken from a different point of
      view. PATIENTS AND METHODS: We examined 36 eyes (18 patients) with the LTS and
      the ONHA. The aim of the study is to examine, whether there are differences in
      the measurement values taken with the LTS and the ONHA investigating the same
      optic disc. RESULTS: 1. There are no significant differences in the measurement
      value of the area of the total disc and the horizontal and vertical diameter of
      the optic disc. 2. The measurement values of the area of the excavation and the
      quotient of the area of excavation to the area of the total disc are
      systematically greater in investigation with the LTS than in investigation with
      the ONHA. This is explained by the different definition of the boundary of the
      excavation. 3. There are significant differences in the measurement values of the
      volume of the excavation, the upper volume of the optic disc, and the maximum
      depth of the excavation. The measurement value of the volume of the excavation is
      systematically greater in investigation with the ONHA than in investigation with
      the LTS. CONCLUSION: Measurement values of the parameters of the optic disc,
      which have the same definition in the LTS and the ONHA--such as the area of the
      total disc and the horizontal and vertical diameter of the optic disc--show no
      significant differences. Thus these parameters are comparable in the LTS and the
      ONHA.

PMID- 7739190
TI  - [Nitrergic reactivity in endothelial cells of human uveal blood vessels].
AB  - BACKGROUND: We investigated the presence of Nicotinamid-adenin-dinucleotid
      phosphat (NADPH)-diaphorase activity in endothelial cells of the human uveal
      vessels, using a histochemical procedure which presumably localizes the reaction
      product nitric oxide. MATERIAL AND METHODS: 11 donor eyes destined for corneal
      transplantation (male: 6; female: 5; age: 56 +/- 8 years) were used within 14 +/-
      7 h postmorten. After removal of the cornea and retinal pigment epithelium, flat
      mounts of the choroid were made. Serial sections, 12-16 microns in thickness were
      cut from the ciliary body and iris using a cryomicrotome. Sections mounted on
      chromalaun-gelatine-coated glass slides, treated according the standard NADPH
      diaphorase reaction and finally mounted in Kayser's glycerol-gelatine prior to
      examination in the light microscope. RESULTS: Human choroidal vascular
      endothelial cells revealed positive NADPH-diaphorase activity, which was detected
      by the presence of punctate blue staining in the cytoplasm. No significant
      difference in distribution pattern or area density was seen amongst small and
      large vessels in either choroid, ciliary body or iris. Ganglion cells in the
      choroid and ciliary body also exhibited NADPH-diaphorase reactivity. CONCLUSION:
      The presence of NADPH-diaphorase reactivity in vascular endothelial and ganglion
      cells of the human choroid suggests a possible nitrergic relaxation mechanism in
      human uveal vasculature.

PMID- 7739191
TI  - [Outer retinitis as an early symptom of subacute sclerosing panencephalitis].
AB  - BACKGROUND: A primary ocular manifestation of subacute sclerosing panencephalitis
      is known and can progress to severe visual deterioration. The rare occurrence of
      the disease makes diagnosis often difficult. CASE REPORT: The lethal clinical
      course of a patient with subacute sclerosing panencephalitis (SSPE) is presented.
      The disease manifested itself with severe ophthalmic symptoms preceding clinical
      and neurological signs and leading to bilateral blindness. The dramatic drop of
      visual acuity was due to a unilateral and later in the course bilateral
      pigmentepitheliopathy of the posterior pole. Inflammatory signs of retinal
      vasculature or inner retinal layers were detected neither clinically nor by
      fluoresceine angiography. A typical blockage of background fluorescence was
      demonstrated in fluoresceine and indocyanine angiography. Within two weeks after
      initial symptoms optic atrophy developed in both eyes. CONCLUSION: The primary
      lesion of retinal pigment epithelium and outer retinal layer were the prominent
      findings in this case. The presence of an outer retinitis of the posterior pole
      should alert the physician to the possibility of subacute sclerosing
      panencephalitis.

PMID- 7739192
TI  - [Sarcoidosis of the optic nerve].
AB  - BACKGROUND: Rarely an affection of the optic nerve is seen as the initial or only
      manifestation of sarcoidosis. Therefore the disease is often diagnosed late. The
      aim of systemic corticosteroid therapy is to prevent progression though it cannot
      yield a cure. PATIENT AND METHOD: Despite a high-dose corticosteroid therapy in
      suspected optic neuritis a 25-year-old woman developed unilateral amaurosis. When
      visual acuity continuously decreased in the second eye a computerized tomography
      was performed, which suggested a tumor of the optic nerve. A biopsy of this
      lesion lead to the diagnosis of Boeck's disease. A long-term corticosteroid
      therapy was initiated. Over the following 9-year period corticosteroids were
      dosed according to the results of regular clinical and perimetrical examinations
      (200 examinations with Octopus-Perimeter 201, program G1). In case of
      deterioration of the visual field higher oral doses were applied. When no
      improvement was achieved by this, corticosteroids were given intrathecally. Under
      this therapeutic regime no systemic side effects were seen. CONCLUSION: In
      unilateral visual loss Boeck's disease should be considered as a rare etiology.
      In case of clear optical media frequent computerized perimetry allows the
      neurologist to adjust the dosage of cortisone and minimize its side effects.

PMID- 7739194
TI  - [Function of diaphragm in the skiascope].

PMID- 7739193
TI  - [Granulomatous process of the optic papilla as an initial sign of systemic
      sarcoidosis].
AB  - Sarcoidosis is a systemic granulomatosis disease of unknown cause that may
      involve many ocular structures in about one third of cases. The findings of a
      posterior uveitis include vitritis, retinal periphlebitis, chorioretinal
      infiltrates, serpiginouschoroiditis, optic nerve atrophy and edema or
      granulomatous infiltration of the papilla. The central nervous system is
      clinically affected in 5 to 15% of cases. Despite several dozen published case
      reports of sarcoidoses of the optic nerve, direct infiltration of this structure
      is considered rare. We describe herein the case of 25-year-old white man whose
      only symptom of systemic sarcoidosis was optic nerve granuloma.

PMID- 7739195
TI  - [Transplantation of retinal components].
AB  - BACKGROUND: The objective of recent animal experimental studies is to substitute
      destroyed or degenerated retina and to improve visual function by transplanting
      retinal components. Mature or immature retinal components were transplanted into
      the subretinal space of different animal species. METHODS: Embryonic and non
      embryonic retina components of different animals or of humans are used as grafts.
      They are transplanted to adult host animals. There is the possibility of
      utilizing a posterior transscleral approach or a vitreoretinal approach. The
      latter offers a better visual control. Transplantation of retinal pigment
      epithelium could rescue photoreceptors in adult rats with inherited or age
      related macular degeneration. RESULTS: After the transplantation it was possible
      to measure significantly higher visual evoked potentials in the transplanted eye
      than in the untreated fellow eye. Additionally, an almost normal pupillary reflex
      was identified. As it is not possible to adequately determine visual acuity in
      rodents, it is necessary to examine, as to whether visual improvement is also
      evident in primates. CONCLUSION: The eye is an immunologically privileged
      location for transplants because of retinal autoantigenic specific
      immunosuppression that protects the transplant from immunologic rejection. Many
      questions regarding operation technique, gaining of transplantation tissue and
      immunoreaction are to be answered before the use is possible on humans. The
      counseling of the patients and the informational policies towards the media
      should be correspondingly retentive.

PMID- 7739196
TI  - [Larger sclerotomies for use of the multiport illumination system do not increase
      the complication risk of vitrectomy].
AB  - PURPOSE: To free both of the surgeon's hands for bimanual work in the vitreous
      cavity, Koch and coworkers developed the multiport illumination system, which,
      however, requires enlarged sclerotomies. PATIENTS AND METHODS: To evaluate the
      safety of the multiport illumination system we analyzed the first postoperative
      year of those 104 vitrectomies, that were performed using this system between
      January and December 1991. It was used only for patients suffering from advanced
      vitreoretinal changes that most likely require bimanual surgery. RESULTS: No
      specific intraoperative or postoperative complications were encountered that
      might possibly have been caused by the multiport illumination system.
      Postoperative fibrinous reactions were noted in the vitreous cavity of 7
      patients, and in the anterior chamber of 15 patients. Rebleeding was observed in
      a total of 17 patients. CONCLUSION: When these complications were compared to
      data from other retrospective studies of vitrectomy and its complications, the
      multiport illumination, system was found to be as safe as conventional devices.

PMID- 7739197
TI  - [Treatment guidelines in various stages of senile retinoschisis].
AB  - BACKGROUND: Concerning the indications, progression in course and the possible
      complications, the different methods of treatment in cases of retinoschisis in
      its different expressions were examined. A staging of senile retinoschisis is
      presented. PATIENTS: Patients' natural course, prophylactic treatment against
      expansion and treatment of retinal detachment were examined. RESULTS: The lateral
      and central barrier of laser or cryo around the schisis is contradictory since a
      progression in direction to the macula is the result. Three of such cases could
      be found. In 6 of 52 cases with prophylactic treatment of an outer layer defect
      with cryo the result was a schisis detachment. In all these cases a retinal
      reattachment was performed with the Custodis procedure. The final anatomic result
      of 95 treated schisis retinal detachments was a 98% success. The symptomatic or
      progressive cases had a little less favourable outcome. CONCLUSIONS: The only
      indication for treatment of a schisis at present is the symptomatic or
      progressive schisis detachment with threatening of the macula. Lateral or central
      barring of a schisis or treatment of the borders of an outer layer retinal break
      should be avoided. The rate of reattachment and the functional results are better
      than in the group of rhegmatogenous retinal detachments including the 50.5%
      schisis retinal detachments without symptoms.

PMID- 7739198
TI  - [Computer controlled analysis of the optic papilla in patients with anterior
      ischemic optic neuropathy].
AB  - BACKGROUND: In patients with non-arteritic anterior ischaemic optic neuropathy
      disc parameters have been measured with a largely objective method (Optic Nerve
      Head Analyzer). We wanted to find out, whether the measurements of different disc
      parameters allow an assertion of predisposition to AION. METHODS: Measurements
      have been done with the Optic Nerve Head Analyzer (ONHA). In 25 patients with
      AION disc area and neuroretinal rim area was measured in the nonaffected fellow
      eye. The results were compared to those of 19 healthy subjects. In 12 of the 25
      patients the disc structure of the AION-eye was measured over time with an
      average of 4 measurements in 16 months. RESULTS: 1) Disc area and neuroretinal
      rim area of the AION-eyes do not differ significantly from those of the healthy
      subjects. 2) Disc area and neuroretinal rim area of the healthy fellow eyes of
      the AION patients were not significantly different from those of the healthy
      subjects. 3) Measurements of disc parameters over time did not show significant
      differences between the parameters of the beginning of AION and after 16 months.
      CONCLUSIONS: Measurements of disc area and neuroretinal rim area with the Optic
      Nerve Head Analyzer do not allow assertions of predisposition to AION.

PMID- 7739199
TI  - [Infectious corneal ulcers--once with endophthalmitis--after photorefractive
      keratotomy with disposable contact lens].
AB  - BACKGROUND: Infections of the cornea with or without involvement of intraocular
      tissues are severe complications after photorefractive keratectomy. We report on
      three cases with ulcerative keratitis and one case with severe endophthalmitis,
      which developed some days after laser treatment. PATIENTS AND METHODS: After 39
      photo-therapeutic and 118 photo-refractive treatments without complications four
      young treated persons suffered from corneal infiltrations. Three of them
      developed severe corneal ulcerations, one a severe endophthalmitis. We used the
      laser machine of the company Schwind (193 nm wavelength, repetition rate 10 Hz,
      fluence 180-200 mJ/cm2). One part of the treatment which all patients had in
      common was the application of a disposable contact lens postoperatively, which
      was worn overnight. THERAPY AND FOLLOW-UP: Because all three patients with
      ulcerations revealed hyphen of fungi in their corneal-scratch material they were
      treated with antifungal agents locally and systemically. Due to the local and
      temporal connection the patient with the endophthalmitis was treated with
      antifungal agents, too. All corneal ulcerations healed with scars similar to a
      haze graded 3 to 4, the eye with the endophthalmitis healed almost completely.
      CONCLUSION: Probably the use of disposable contact lenses postoperatively,
      especially the overnight wear, during an extremely hot and humid summer lead to
      the described severe infections of the eyes after the "traumatisation" of the
      cornea by the excimer laser. A known higher concentration of Aspergillus in the
      air due to renovations of buildings in the clinical area might have been an
      additional negative effect. The avoidance of the use of disposable contact lenses
      postoperatively, especially the overnight wear, is emphasized.

PMID- 7739200
TI  - PCNA expression and nucleolar organizer regions in malignant melanoma and nevus
      cell nevus.
AB  - The histogenesis of malignant melanoma with particular reference to the role of
      melanocytic nevus is still controversial in oncological pathology. In order to
      differentiate between the proliferative activity of malignant melanomas and
      benign melanocytic tumors, immunohistochemical analysis was carried out. We used
      monoclonal antibody PC10 to identify the Proliferating Cell Nuclear Antigen
      (PCNA), a highly conserved 36 KD acidic nuclear protein which correlates with
      cell proliferation, and the AgNOR method to stain the Nucleolar Organizer Regions
      (NORs) whose number and configurations may reflect protein synthesis activity. 47
      cases of primary melanoma, 63 metastatic melanoma lesions, and 23 cases of nevi
      are included in this study. Spitz nevi showed a higher index of cell
      proliferation compared with other common benign nevi but a much lower index
      compared with malignant melanoma cells. The metastatic lesions of malignant
      melanomas had a higher index of proliferation and activity of cells than the
      primary lesions. Skin-metastatic lesions had higher indexes of cell proliferation
      and NOR activity than lymph node-metastatic lesions. These results support the
      idea that metastatic melanoma cells are derived from a more advanced stage of
      tumor progression. These data suggest that the combination of PCNA and AgNOR is
      an useful marker for differentiating benign melanocytic tumors from malignant
      melanomas.

PMID- 7739201
TI  - Cultured osteoblast synthesize nitric oxide in response to cytokines and
      lipopolysaccharide.
AB  - Nitric oxide (NO) is generated from L-arginine by NO synthase. NO has been
      reported to be produced by a variety of cell types such as vascular endothelial
      cells, macrophages, neutrophils and articular chondrocytes. A recent report
      demonstrated that NO inhibits osteoclast (OC) function and, in this way, is
      critically associated with bone metabolism. In the present study we have studied
      NO synthesis by osteoblasts (OBs). OB cell line, MC3T3-E1, was cultured with the
      various cytokines for 72 hrs. Nitrite, a stable endproduct of cell-generated NO,
      in the culture supernatant was then determined by using a spectrophotometric
      method based on Griess reaction. IL-1 alpha increased nitrite release in a dose
      dependent fashion and a significant enhancement (p < 0.01) was attained at 10
      U/ml. OBs released 14.2 nmol/4.0 x 10(4) cells of nitrite after 72 hrs
      stimulation by 100 U/ml IL-1 alpha. In contrast IL-1 beta, TNF-alpha and INF
      gamma failed to affect NO synthesis by MC3T3-E1. The results suggest that OBs
      produce NO in response to IL-1 alpha and OB-induced NO may play a role in OB-OC
      interaction in the inflammatory process.

PMID- 7739202
TI  - A study of the motor neuron pool of the superior rectus muscle in albino rats by
      retrograde fluorescent double labeling technique.
AB  - Recent investigations revealed the localized distribution of the motoneuron
      subgroups within the mammalian oculomotor nucleus. In this study, we examined the
      motor neuron pool of the superior rectus muscle (SR) in 12 albino rats by
      injecting the retrograde fluorescent tracers Fluoro-Gold (FG) into one SR and Dil
      into the contralateral SR. We also examined the topographic and functional
      correlation between the neurons controlling the muscles of the upward gaze, i.e.,
      SR and the inferior oblique muscle (IO) in another 5 albino rats by means of the
      same tracers. Our results demonstrated that: 1) the average total number of the
      neurons in the motor neuron pool of SR was 322.7 +/- 40.1; 2) topographically,
      about 94.65% of the motoneurons controlling SR were located in the contralateral
      side, while the remaining 5.35% lay ipsilaterally; 3) all the IO motoneurons were
      present on the same side of the muscle they innervate; 4) the motoneurons of SR
      and IO did not form separate subnuclei, but were intermingling with each other;
      5) functionally, about 94.59%, 4.26% and 1.15% of the total motoneurons in the SR
      subnucleus of either oculomotor nucleus were projecting contralaterally,
      ipsilaterally and bilaterally, respectively; 6) although the distribution of the
      perikarya was not homogeneous, the bilaterally projecting (i.e., to both SR)
      cells were disposed centrally, and their double labeling indicated that their
      axons innervate the bilateral SR via axonal bifurcation and/or collateral
      branching; and 7) the motoneurons of SR and IO were functionally segregated from
      each other as no bilaterally projecting neurons (i.e., to SR and IO) were found.

PMID- 7739203
TI  - A relation between c-myc expression and prognosis of leukemia patients in
      Indonesia.
AB  - Overexpression of c-myc, c-myb and c-fos proto-oncogene has been observed in many
      leukemia cells. However, a relation between those oncogene expressions and
      prognosis of the leukemia is not known in Indonesia. In order to elucidate the
      relation, expression of those oncogenes in leukemia cells from 52 patients in
      Indonesia was examined by Northern blot analysis and was compared with prognosis
      of the disease. The leukemia patients who survived for more than 2 years were 37%
      of the 52 patients. Many of the samples expressed c-myc mRNA (92%). Although
      strong expression of c-myb and c-fos mRNA was detected in the samples (c-myb
      expression in 35% of the leukemia cells and c-fos in 52%), those co-expressions
      with c-myc mRNA did not alter the prognosis. On the contrary, all of the 4
      patients suffering from leukemia which did not express c-myc mRNA survived for
      more than 2 years. Therefore, c-myc expression in leukemia cells may be used as
      an indicator for deciding prognosis of the leukemia patients in Indonesia.

PMID- 7739204
TI  - Evaluation of computerized electrocardiographic interpretations in a community
      hospital.

PMID- 7739205
TI  - Digoxin dosing: an alternate approach.

PMID- 7739206
TI  - Domestic violence: a perinatal and pediatric risk factor.

PMID- 7739207
TI  - Comprehensive care of the cleft lip and palate patient.

PMID- 7739208
TI  - Otolaryngology.

PMID- 7739209
TI  - Atrial myxoma: diagnosis and treatment.

PMID- 7739210
TI  - Recent developments in electroconvulsive therapy.

PMID- 7739211
TI  - A model of error propagation in the presence of an error-enhancing drug.
AB  - A mathematical model is considered that describes error propagation in protein
      synthesis, with emphasis on the role of an error-enhancing drug such as
      streptomycin. The subject of error propagation has been investigated in a number
      of works since an original proposal by Orgel in 1963. From experiments, it is
      known that streptomycin given to a bacterium culture in small concentration
      increases the error level, but at a certain concentration threshold the bacteria
      die. This two-fold behavior has, in some papers, lead to the proposal that
      another effect of the drugs besides that of error propagation leads to the death
      of the bacteria. In the present work, we use a model related to kinetic models of
      selection in protein synthesis which include the combined effect of ribosome and
      synthetase action. The model shows very clear threshold effects: for small values
      of the parameter that represents the drug action, a stable situation is found
      that has an increased error level but still attains a rather high accuracy. At a
      certain threshold, this is no longer maintained. The main emphasis here is on the
      time evolution of relevant parameters, and it is also shown how this can be quite
      drastic: the accuracy may decrease rather smoothly to a critical point, where it
      is drastically lost and where the bacteria may die out very suddenly.

PMID- 7739212
TI  - The multiregional and single origin hypotheses of the evolution of modern man: a
      reconciliation.
AB  - A current debate opposes two theories of the origin of modern man. One view is
      that modern Homo sapiens emerged from Africa relatively recently, most probably
      within the last two or three hundred thousand years (Wilson & Cann, 1992, Sci.
      Am. 266(4), 22-27). The opposing view is that modern man has resulted from
      parallel evolution in different regions, producing convergent modernization of
      local populations over the last million years or so--the multiregional model
      (Frayer et al., 1993, Am. Anthrop. 95, 14-50). Proponents of both views believe
      that their interpretations are irreconcilable. The object of the present paper is
      to describe a genetic mechanism--mitochondrial exclusion--which offers a basis
      for a model of human evolution that is compatible with the evidence adduced for
      both contemporary views. The model proposes a mechanism by which complete
      replacement of archaic mitochondrial DNA may have occurred in a population
      produced by recent admixture of archaic and modern types of man.

PMID- 7739213
TI  - A model study on the influence of a slowly activating potassium conductance on
      repetitive firing patterns of muscle spindle primary endings.
AB  - The general mathematical model of Frankenhaeuser and Huxley, which describes the
      generation of action potentials in myelinated nerve fibres, has been used as a
      kernel for a model of a sensory nerve ending. Two types of modifications were
      implemented. First, the four original permeability constants (those of potassium,
      sodium, non-specific and leak) were changed simultaneously (using an automated
      tuning algorithm), in order to introduce low-frequency repetitive firing
      capability (down to 15 Hz), keeping the deviations from the original values as
      small as possible. Second, a slow potassium conductance was added, in order to
      model slow processes (like accommodation) with time constants longer than those
      required to simulate short-lasting action potentials. Sensory stimuli were
      simulated as changes in passive conductance. The model displayed the following
      properties, which are typical of many sensory endings in general and of muscle
      spindle primary endings in particular: (i) The range of sustained repetitive
      firing was extended into the domain of low discharge rates, so as to span the
      entire physiological range (from 2 to 700 sec-1). (ii) The relation between
      firing rate and receptor potential was roughly linear over the full range of
      firing. (iii) Following a step increase of stimulus, the firing rate showed
      adaptation with a time constant of about 70 msec. (iv) Sudden reduction of the
      stimulus was followed by post-release silence. (v) Following a step increase of
      stimulus, the receptor potential showed a short dynamic peak. (vi) Following a
      step decrease of stimulus, the receptor potential displayed a post-release
      undershoot and recovery with a time constant of approximately 100 msec. (vii)
      With sinusoidal stimuli the receptor potential showed band-pass filter properties
      with phase advance below and phase lag above 12 Hz and a peak in gain at about 20
      Hz. Thus the present equations adequately describe a range of known properties of
      muscle spindle primary endings. Based on minimal modification and extension of
      the Frankenhaeuser-Huxley model of action potential generation in myelinated
      fibres, they constitute a theory of sensory encoding. This theory is further
      corroborated by the experimental evidence of the presence of calcium-activated
      potassium channels in numerous sensory--including primary spindle--endings.

PMID- 7739215
TI  - A model of chiasma reduction of closely formed crossovers.
AB  - A model of chiasma reduction is developed, evaluated by computer simulation and
      discussed in relation to the evolution of interference. The model assumes that
      adjacently formed crossovers can interact, if there is incomplete sister
      chromatid cohesion between them, and give rise to a reduced number of chiasmata.
      In the absence of crossover position interference this leads to a considerable
      risk of non-disjunction for an average sized chromosome. It is suggested that an
      important function of crossover interference is to reduce this effect. The
      question is raised whether chiasma reduction takes place today. Some available
      cytological data can be interpreted as showing that chiasma reduction occurs in
      normal meiosis. The possibility of chiasma reduction therefore needs further
      attention.

PMID- 7739214
TI  - Alternans and period-doubling bifurcations in atrioventricular nodal conduction.
AB  - A theoretical model, formulated as a finite difference equation is proposed for
      rate-dependent conduction properties of the atrioventricular (AV) node. The AV
      nodal conduction time, which is defined as the time interval from the atrial
      activation to the activation of the bundle of His, depends on the history of
      activation of the node. The theoretical model, which incorporates physiological
      concepts of recovery, facilitation and fatigue, accurately predicts a variety of
      experimentally observed complex rhythms of nodal conduction. In particular,
      alternans rhythms, in which there is an alternation in conduction time from beat
      to beat, are associated with period-doubling bifurcations in the theoretical
      model.

PMID- 7739216
TI  - Consumer power as the major evolutionary force.
AB  - Each trophic level in evolving ecosystems can behave as either a supplier toward
      the downstream of trophic energy flow or a consumer toward the upstream, or an
      arbitrary mixture of the two. We show that each trophic level behaves almost
      completely as a consumer in evolutionarily sustainable ecosystems. The present
      prevalence of consumers in evolving ecosystems derives from a model trophic
      dynamics minimizing the artificial constraints to be applied arbitrarily.

PMID- 7739217
TI  - Phylogenetic invariants for more general evolutionary models.
AB  - An invariant Q of a tree T under a k-state Markov model, where a generalized time
      parameter is identified with the E edges of T, allows us to recognize whether
      data on N observed species (usually, N DNA sequences, one from each species) can
      be associated with the N leaves of T in the sense of having been generated on T
      rather than on any other N-leaf tree. The form of the generalized time parameter
      is a positive determinant matrix in some semigroup S of Markov matrices. The
      invariance is with respect to the choice of the set of E matrices in S, one
      associated with each of the E edges of T. The parametric form of S represents a
      model of the evolutionary process. In this paper, we apply a general method of
      finding invariants of a parametrized functional form to find low-degree
      polynomial invariants for different models. Quadratic invariants are obtained for
      the Kimura two-parameter model, for a model allowing evolutionary dependence
      between positions in the sequences and for an asymmetric model that allows for A
      + T versus G + C asymmetries in DNA base composition. Those invariants are found
      for trees (unrooted in case of the Kimura model and rooted for the others) with N
      = 3 or N = 4 terminal vertices. We also find cubic invariants for a ten-parameter
      model with k = 4 states, for rooted trees with N = 4. In each case, we use
      implicit function theory to predict the number of algebraically independent
      invariants and then use this prediction to guide a systematic search for
      algebraic dependence within the set of invariants produced by our method.

PMID- 7739218
TI  - Were RNA replication and translation directly coupled in the RNA (+protein?)
      World?
AB  - The ribosome is proposed to have evolved from an ancestor that simultaneously
      replicated and translated template RNA. At its decoding site, this ancestor to
      the ribosome carried a ribozyme that assembled product RNA by sequentially
      ligating anticodon triplets excised from tRNAs. This ribozyme was the ancestor of
      the Group I introns, which are still present on some ribosomal RNA precursors.
      Coupling of reversible RNA replication by transesterification with the
      thermodynamically favourable process of transpeptidation provides a rationale for
      the evolution of the complete ribosome as a replicase for large RNAs in the RNA
      (+protein?) world. A detailed and experimentally verifiable mechanism can be
      proposed for simultaneous replication and translation. Sequence requirements for
      recognition of the decoding complex as a substrate helix by these ribozymes are
      consistent with earlier models for the origin of the genetic code, but require an
      indirect mode for ribosomal self-replication. This proposal has the potential to
      explain the location of Group I introns in the anticodon loops of some tRNAs.

PMID- 7739219
TI  - Models of the liver pentose cycle.
AB  - Simple and complete models of the classical liver pentose cycle, and a model of
      Williams' proposed "L-type" pentose cycle, are compared. All extant experimental
      data on well-oxygenated whole cell systems can be fitted to the predicted output
      of the complete classical pentose cycle model; however, there are gross
      discrepancies between key experimental data and Williams' proposed scheme. The
      complete classical model allows isotopic reversibility in the non-oxidative
      segment of the cycle, but none of the reversible enzymes are extremely close to
      isotopic equilibrium. General approaches are presented to estimate the isotopic
      reversibility of most enzymic steps, without requiring isolation of the
      intermediates, present in some cases at very low concentrations. The isotopic
      reversibility of the non-oxidative pathway causes only minor errors in the
      equations used to estimate liver pentose cycle flux, which were based on simple
      unidirectional models.

PMID- 7739221
TI  - Sexual reproduction: the dawn of enabling chromosome maneuvers.

PMID- 7739220
TI  - The creatine kinase equilibrium, free [ADP] and myosin ATPase in vascular smooth
      muscle cross-bridges.
AB  - MgADP has a more pronounced effect on the relaxation behaviour in tonic vascular
      smooth muscle compared to phasic smooth muscle. An apparent dissociation constant
      of 1.3 microM has been reported for a high affinity binding site of vascular
      smooth muscle cross-bridges. For this high affinity to have an effect on the low
      energy costs of tension maintenance (latch) it would require that free [ADP] in
      the region of the contractile proteins (at least sometimes) be as low as 1.3
      microM. We ask, in this report, whether [ADP] could be as low as 1.3 microM in
      vascular smooth muscle. If creatine kinase (CK) is at equilibrium, then
      micromolar [ADP] is incompatible with measured concentrations of phosphocreatine
      (PCr), free creatine (Cr) and ATP, which entail a mean equilibrium [ADP] of
      around 18 microM. But CK may not be quite at equilibrium: if there is net PCr
      synthesis at the mitochondrion, then maintenance of the steady-state requires
      that there be net PCr hydrolysis in the region of the contractile proteins up to
      or equal to the rate of myosin ATPase. We derive a simple relationship between
      net flux and displacement from equilibrium which we use to argue that an [ADP] of
      1.3 microM at the contractile proteins would drive significant net PCr synthesis,
      incompatible with normal contractile function. Thus the CK system holds [ADP] at
      about 18 microM near the contractile proteins in vascular smooth muscle. We
      conclude that smooth muscle [ADP] cannot be far from equilibrium and that a role
      for ADP (at the low micromolar level) in controlling smooth muscle relaxation is
      unlikely.

PMID- 7739222
TI  - Usage and bioassays in Phyllanthus (Euphorbiaceae). IV. Clustering of antiviral
      uses and other effects.
AB  - A number of species of the genus Phyllanthus (Euphorbiaceae) have been tested for
      their efficacy as antivirals, partly on the basis of references to traditional
      usage for the treatment of diseases possibly having a viral origin. There are
      also many references to indigenous uses and to laboratory assays for other
      biological activities in this large genus (550+ species). These citations have
      been arranged by subgenus, section, subsection and species and have been
      published in three previous papers. This paper summarizes selected clustering of
      usage and effect by subgeneric taxa. Consideration of the data from ethnobotany,
      in vitro assays and clinical trials supported the presence of some type of
      biological activity(s) particularly within the subgenus Phyllanthus. Although the
      herbaceous species of subgenus Phyllanthus have been extensively used to treat
      jaundice, and have generally inhibited hepadnavirus DNAp, effects on chronic
      infection with hepatitis B virus (HBV) or related viruses have generally been
      negative. Alternative explanations for the wide usage have been little explored.
      Other medical categories suggested possible leads for research, or possibly,
      herbal or galenic remedies with bona fide effects. In most cases, the data remain
      suggestive but not conclusive.

PMID- 7739223
TI  - The use of isolated functional heart to pharmacologically characterize active
      ingredients in the aqueous extracts of Mareya micrantha.
AB  - Aqueous extracts of Mareya micrantha are used as folk medicine in West Africa.
      However, no systemic investigation directed to the identification of the active
      ingredients in M. micrantha has been done. Therefore, this study investigated the
      effects of M. micrantha on the cardiac contractility of the isolated frog heart.
      Also, two sequential fractions from M. micrantha were separated and their effects
      on cardiac contractility investigated. M. micrantha concentration-dependently
      suppressed cardiac contractility. Separation of the cardioactive components in
      series by column chromatography (Sephadex G-50, Column 2.5 x 30 cm and 1 x 20 cm)
      produced two fractions which facilitated a leftward shift of the dose-response
      curve of the cardiodepressant effects suggesting that column chromatograph is
      effective in the isolation of the cardioactive ingredients in M. micrantha. The
      data suggest that M. micrantha contains cardioactive components and that
      contractions of the isolated functional frog heart can be used as a
      pharmacological activity marker during the process of isolation of cardioactive
      ingredients in M. micrantha.

PMID- 7739224
TI  - Ethiopian traditional herbal drugs. Part I: Studies on the toxicity and
      therapeutic activity of local taenicidal medications.
AB  - The quantitative toxicities of 33 taenicidal herbal drugs are presented,
      expressed as their intraperitoneal LD50 values in mice and their respective
      median effective oral dose and worm expulsion time in humans. Rank orders of
      toxicity, taenicidal potency and worm expulsion time of the herbal medications
      are indicated along with a discussion of their respective therapeutic merits and
      untoward effects. On the basis of considerations of lower toxicity, higher
      potency and shorter worm expulsion time, the taenicidal herbal medications are
      arranged in decreasing rank order of preference. Other therapeutic uses of the
      herbs are also presented and discussed.

PMID- 7739225
TI  - Mutagenicity, insecticidal and trypanocidal activity of some Paraguayan
      Asteraceae.
AB  - The insecticidal, moulting inhibition and trypanocidal effects of crude extracts
      of 7 Paraguayan Asteraceae were evaluated on Triatoma infestans and bloodstream
      forms of Trypanosoma cruzi, respectively. Both mutagenicity and toxicity were
      evaluated by sister chromatid exchange (SCE) in human peripheral lymphocyte
      culture and by the lethality test of Artemia salina. The ethanolic extracts from
      Chromolaena christieana (stem and bark), Achyrocline satureoides (leaves and
      flowers) and Mikania cordifolia (root and stem), at a concentration of 250
      micrograms/ml, showed the highest percentage of lysis on bloodstream forms of
      Trypanosoma cruzi. The extracts of Chromolaena christieana and Achyrocline
      satureoides also presented high mutagenic and toxic capacity when they were
      evaluated by the SCEs assay and Artemia salina test, respectively. Insecticidal
      activity was only observed in the hexane extract of flowers of Achyrocline
      satureoides (45% of mortality), when 0.05 microgram of crude concentration was
      applied on Triatoma infestans. The ethanolic extracts of stem from Mikania
      cordifolia and Vernonia brasiliana inhibited the moulting of Triatoma infestans
      when it was compared with their controls. Since no ethnobotanical information on
      these plants has been found related to similar use in Paraguay, our findings
      suggest, for the first time, the potential anti-trypanocidal and moulting
      inhibition of these Asteraceae.

PMID- 7739226
TI  - The antiamoebic effect of a crude drug formulation of herbal extracts against
      Entamoeba histolytica in vitro and in vivo.
AB  - The antiamoebic effect of a crude drug formulation against Entamoeba histolytica
      was studied. In the traditional system of medicine in India, the formulation has
      been prescribed for intestinal disorders. It comprises of five medicinal herbs,
      namely, Boerhavia diffusa, Berberis aristata, Tinospora cordifolia, Terminalia
      chebula and Zingiber officinale. The dried and pulverized plants were extracted
      in ethanol together and individually. In vitro amoebicidal activity was studied
      to determine the minimal inhibitory concentration (MIC) values of all the
      constituent extracts as well as the whole formulation. The formulation had a MIC
      of 1000 micrograms/ml as compared with 10 micrograms/ml for metronidazole. In
      experimental caecal amoebiasis in rats the formulation had a curative rate of 89%
      with the average degree of infection (ADI) reduced to 0.4 in a group dosed with
      500 mg/kg per day as compared with ADI of 3.8 for the sham-treated control group
      of rats. Metronidazole had a cure rate of 89% (ADI = 0.4) at a dose of 100 mg/kg
      per day and cured the infection completely (ADI = 0) when the dosage was doubled
      to 200 mg/kg per day. There were varying degrees of inhibition of the following
      enzyme activities of crude extracts of axenically cultured amoebae: DNase, RNase,
      aldolase, alkaline phosphatase, acid phosphatase, alpha-amylase and protease.

PMID- 7739227
TI  - Croton zehntneri: possible central nervous system effects of the essential oil in
      rodents.
AB  - The effects of essential oil of Croton zehntneri (Euphorbiaceae), orally
      administered were studied on behavioral parameters using rats and mice. The oil
      suspension did not modify pentobarbital induced-hypnosis, stereotypic behavior,
      catalepsy and amphetamine-induced hypermotility. The open-field behaviors were
      decreased and the minimal convulsant dose of pentylenetetrazole was increased.

PMID- 7739228
TI  - Effects on rat uterine and aorta strip smooth muscle of Thymus leptophyllus
      extract.
AB  - The diethylether extract from Thymus leptophyllus was found to be more active on
      uterine smooth muscle than on aorta strips. Rat uterus experiments with and
      without extracellular calcium, yielded similar IC50 values. A nonspecific
      mechanism for the relaxant activity can therefore be postulated. In rat aorta and
      in the presence of extracellular calcium the extract inhibited the contractile
      response induced by K+ depolarizing solution and had a less inhibitory effect on
      noradrenaline (NA) contraction. In a Ca(2+)-free solution the extract strongly
      reduced the Ca(2+)-release induced by NA, but it did not affect the transient
      contraction caused by caffeine (CAF).

PMID- 7739229
TI  - Screening of Uruguayan medicinal plants for antimicrobial activity.

PMID- 7739230
TI  - Comparative antimicrobial study of the resinous exudates of some Chilean
      Haplopappus (Asteraceae).
AB  - The antimicrobiol properties and preliminary chemical information of the resinous
      exudates from twigs and leaves of nine Haplopappus species from Chile: H.
      diplopappus; H. anthylloides; H. schumannii; H. cuneifolius; H. velutinus; H.
      uncinatus; H. multifolius, H. illinitus and H. foliosus are presented. The
      results show that those species of genus Haplopappus share similar antimicrobial
      activities although they differ dramatically in the chemical composition.

PMID- 7739231
TI  - Bronchogenic cysts of the mediastinum.
AB  - During a 25-year period 69 patients whose ages ranged from 1 day to 64 years were
      treated for bronchogenic cyst of the mediastinum. The male-to-female sex ratio
      was 1:0.76. The cysts were symptomatic in 63.7%, compressive in 43.4%, and life
      threatening in 2.8% of cases. Symptoms and signs of compression were more
      frequent in infants and children than in adults. Such symptoms and signs were
      more dependent on the location of the cyst than on its volume. The preoperative
      diagnosis was wrong in 16% of cases. The cysts were approached through
      thoracotomy in 67 cases, including one conversion from thoracoscopy, and through
      cervicotomy and mediastinoscopy in one case each. The cysts opened into the
      respiratory tract in five cases. No communication with the esophageal lumen was
      observed. The cystic contents were apparently infected in three cases, but
      samples remained sterile at culture. There was one hospital death caused by a
      centrally located compressive cyst that was undiagnosed at thoracotomy. The
      postoperative morbidity rate was 13.4%. There were no further symptoms after
      operation in children, but five adults reported continuing pain or dyspnea.
      Resection of bronchogenic cysts is recommended because of uncertainties in
      diagnosis and in evolution.

PMID- 7739232
TI  - Early failure of aortic valve conservation in aortic root aneurysm.

PMID- 7739234
TI  - First clinical use of a heparin removal device: an alternative to protamine.

PMID- 7739233
TI  - Lidoflazine and myocardial protection.

PMID- 7739235
TI  - Preliminary results of deferoxamine and L1 treatment of spinal cord ischemia.

PMID- 7739236
TI  - Relief of complex left ventricular outflow tract obstruction with pulmonary
      autografts.

PMID- 7739237
TI  - Surgical interruption of the superior vena cava.

PMID- 7739238
TI  - One-lung ventilation during surgical procedures on the main bronchus and carina.

PMID- 7739239
TI  - Supernumerary heart valves.

PMID- 7739240
TI  - A thoracic surgeon's tale of two cities.

PMID- 7739241
TI  - Midline one-stage complete unifocalization and repair of pulmonary atresia with
      ventricular septal defect and major aortopulmonary collaterals.
AB  - Traditionally patients with pulmonary atresia, ventricular septal defect,
      diminutive or absent central pulmonary arteries, and multiple aortopulmonary
      collaterals have been managed by staged procedures necessitating multiple
      operations. We have taken a different approach to this lesion. Between August
      1992 and March 1994, ten patients aged 1.43 months to 37.34 years (median 2.08
      years) at the severe end of the morphologic spectrum of this lesion underwent a
      one-stage complete unifocalization and repair from a midline sternotomy approach.
      The median Nakata index of true pulmonary arteries was 50.0 (range 0 to 103.13)
      and they provided vascular supply to up to nine lung segments (median 5
      segments). The number of collaterals per patient ranged from two to five with a
      median of four. The collaterals provided vascular supply to a median of 15 lung
      segments per patient (range 11 to 20). Complete unifocalization was achieved in
      all patients with emphasis on native tissue-to-tissue connections via anastomosis
      of collaterals to other collaterals and to the native pulmonary arteries. In only
      one patient (37.34 years old) was it necessary to use a non-native conduit for
      peripheral pulmonary artery reconstruction. The ventricular septal defect was
      left open in one patient (5 years old) because of diffuse distal hypoplasia and
      stenosis of the pulmonary arteries and the collaterals. The postrepair peak
      systolic right ventricular/left ventricular pressure ratio ranged from 0.31 to
      0.58 (median 0.47). There were no early deaths. Complications were bleeding
      necessitating reexploration in one patient, phrenic nerve palsy in three
      patients, and severe bronchospasm in three patients. Follow-up (median 8 months,
      range 2 to 19 months) was complete in all patients. One patient was reoperated on
      for pseudoaneurysm of the central homograft conduit and then again for stenosis
      of the left lower lobe collateral. After this last operation at 13 months after
      the initial repair she died of a preventable cardiac arrest caused by
      pneumothorax. The patient with open ventricular septal defect underwent balloon
      dilation of the unifocalized pulmonary arteries, with a current
      pulmonary/systemic flow ratio of 1.4 to 1.8:1, and is awaiting ventricular septal
      defect closure. One other patient underwent balloon dilation of the reconstructed
      right pulmonary artery, with a good result. All survivors (9/10) are clinically
      doing well. This approach establishes normal cardiovascular physiology early in
      life, eliminates the need for multiple systemic-pulmonary artery shunts and use
      of prosthetic material, and minimizes the number of operations required.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7739242
TI  - Successful use of transesophageal echocardiography during extracorporeal membrane
      oxygenation in infants after cardiac operations.
AB  - We report the use of transesophageal echocardiography in infants after cardiac
      operations while supported on extracorporeal membrane oxygenation. In all
      patients transesophageal echocardiography provided valuable information when
      standard transthoracic echocardiographic evaluation was limited by poor acoustic
      windows. This report describes the application of transesophageal
      echocardiography during extracorporeal membrane oxygenation after cardiac
      operations.

PMID- 7739243
TI  - The effects of cyanosis on myocardial blood flow, oxygen utilization, and lactate
      production in dogs.
AB  - To elucidate differences in myocardial blood flow and metabolism between cyanotic
      and normal hearts, a model of chronic cyanosis was created in five adult mongrel
      dogs by anastomosing the inferior vena cava to the left atrium. After 6 to 9
      months, myocardial blood flow, the ratio of subendocardial to subepicardial flow,
      oxygen consumption, oxygen extraction ratio, and lactate consumption in these
      cyanotic dogs and five control dogs were determined under baseline conditions and
      during pharmacologic stress with isoproterenol (0.2 micrograms/kg/min).
      Radioactive microspheres were used to determine left and right ventricular blood
      flow rates, and arterial and coronary sinus differences in oxygen and lactate
      levels were measured. At baseline and during stress, oxygen consumption and
      oxygen extraction ratios were identical in control and cyanotic hearts. Total
      myocardial blood flow was increased with stress and did not differ between
      cyanotic and control hearts. Left ventricular muscle from cyanotic hearts did
      exhibit lower endocardial/epicardial blood flow ratios than those of control
      hearts at rest, and the relative subendocardial flow decreased further with
      stress. During isoproterenol infusion, myocardial lactate production, indicative
      of anaerobic metabolism, was evident in two of five cyanotic animals and none of
      the control dogs. The relative subendocardial ischemia and its further
      aggravation by stress in cyanotic hearts may contribute to the pathophysiologic
      basis of myocardial dysfunction in cyanotic heart disease.

PMID- 7739244
TI  - Use of autologous umbilical artery and vein for vascular reconstruction in the
      newborn.
AB  - Autologous umbilical artery and vein were evaluated as vascular conduits in
      newborn lambs. Eight newborn lambs were delivered transabdominally under sterile
      conditions at term. The umbilical artery and vein were dissected from the cord
      and stored in culture media. On the same day, each lamb underwent bilateral
      superficial femoral artery transection and reconstruction. Nine arteries were
      reconstructed with autologous umbilical vein interposition grafts, five with
      umbilical artery interposition grafts, and two by primary native artery
      anastomosis. After the birth weight of the lambs quadrupled (37 to 45 days), they
      were killed and all grafts and anastomoses were examined grossly and
      histologically. At the conclusion of the study, both native artery anastomoses
      (2/2) were patent. Five umbilical vein (5/9) and two umbilical artery (2/5)
      autografts were also widely patent. Patent autografts retained an intact
      endothelium supported by a viable media. The nonpatent autografts had become
      atrophic remnants displaying histologic signs of early closure. Graft failures
      are attributed to the extreme vasoactive nature of the umbilical vessels. These
      preliminary results suggest that umbilical vessels may be useful as a vascular
      autograft if the vasoactive nature of these vessels can be overcome during the
      immediate perioperative period.

PMID- 7739245
TI  - Long-term results of valve replacement with the St. Jude Medical prosthesis.
AB  - To assess with truly long follow-up the long-term results of valve replacement
      with the St. Jude Medical prosthesis (St. Jude Medical, Inc., St. Paul, Minn.),
      we reviewed the case histories of the first 1112 patients undergoing 1244 valve
      replacements with this valve between June 12, 1978, and June 12, 1987: 690 male
      (62%) and 422 female patients, mean age 56 years. A total of 773 patients (69%)
      had the aortic valve replaced, 207 (19%) the mitral valve, and 132 (12%) the
      aortic and mitral valves. There were 42 hospital deaths (3.8%). Follow-up was
      97.5% complete (8988 patient-years). There were 213 late deaths. Ninety-one (43%)
      were considered valve-related: sudden death, n = 27; anticoagulant-related
      hemorrhage, n = 22; thromboembolism, n = 19; prosthetic valve endocarditis, n =
      13; valve thrombosis, n = 9; and noninfectious perivalvular leak, n = 1. Overall
      actuarial survival, including hospital mortality, was 68% +/- 6% (95% confidence
      limits) 14 years after the operation. Linearized rates of late valve-related
      events were as follows: thromboembolism, 1.09% per patient-year; anticoagulant
      related hemorrhage, 0.94% per patient-year; prosthetic valve endocarditis, 0.32%
      per patient-year; valve thrombosis, 0.33% per patient-year; and perivalvular
      leak, 0.19% per patient-year. Actuarial freedom, at 14 years, from
      thromboembolism was 89% +/- 3%, anticoagulant-related hemorrhage 83% +/- 8%,
      valve thrombosis 97% +/- 1%, and reoperation 95% +/- 3%. Actuarial freedom from
      all valve-related deaths and valve-related morbidity and mortality, at 14 years,
      was 84% +/- 6% and 61% +/- 8%, respectively. We conclude that, because of its low
      thrombogenicity, low incidence of valve-related events, and low valve-related
      mortality, the St. Jude Medical valve is one of the best performing mechanical
      prosthesis currently available. Nevertheless, the late valve-related
      complications and deaths illustrate that the quest for a "perfect" prosthesis
      remains unfulfilled.

PMID- 7739246
TI  - Stentless porcine aortic root: valve of choice for the elderly patient with small
      aortic root?
AB  - The Medtronic Freestyle bioprosthesis is a stentless porcine aortic root cross
      linked in dilute glutaraldehyde solution with stress-free fixation for the valve
      leaflets. It has been treated by a process in which amino oleic acid is used to
      reduce the potential for calcification. As a complete aortic root, it has the
      same versatility as the aortic homograft but has the advantage that it is readily
      available in all sizes to the implanting surgeon. Between January 1993 and May
      1994, we implanted 64 Freestyle bioprostheses as aortic valve replacements using
      a freehand technique; 5 size 19 mm, 15 size 21 mm, 16 size 23 mm, 13 size 25 mm,
      and 15 size 27 mm valves were used. There were 35 men and the mean age was 75.7
      years (64 to 84 years). The operative mortality was 3.1% (2/64). Echocardiograms
      at the time of discharge revealed mean aortic valve gradients ranging from 18.2
      mm Hg for 19 mm to 10.3 mm Hg for 27 mm valves. Effective orifice areas ranged
      from 1.0 cm2 for 19 mm to 2.0 cm2 for 27 mm valves. No patient had more than
      trace aortic insufficiency. Our early experience with this new stentless
      bioprosthesis shows it to have excellent hemodynamics especially in the smaller
      valve sizes. Using this valve in patients who have a small aortic root and
      require a tissue valve avoids the need for aortic root enlargement procedures.

PMID- 7739247
TI  - In-hospital and long-term outcome after porcine tricuspid valve replacement.
AB  - Porcine bioprostheses are often used for tricuspid valve replacement, yet the
      long-term outcome after this procedure is not well documented. Therefore, the
      records of 129 patients undergoing tricuspid valve replacement with Carpentier
      Edwards (n = 88) or Hancock (n = 41) prostheses between 1975 and 1993 were
      reviewed. The operation required a repeat median sternotomy in 66 of 129 (51%)
      patients, whereas 67 of 129 (52%) underwent double or triple valve replacement.
      Operative mortality was 14% (2/14) in patients undergoing first-time isolated
      tricuspid valve replacement and 27% (35/129) overall. Survival at 5, 10, and 14
      years was 56% +/- 5%, 48% +/- 5%, and 31% +/- 9%, and freedom from tricuspid
      reoperation at 5, 10, and 14 years was 96% +/- 3%, 93% +/- 4%, and 49% +/- 17%.
      No valve thrombosis was observed. In this largest reported series of porcine
      bioprostheses in the tricuspid position, long-term freedom from valve-related
      events was excellent because of a low incidence of valve thrombosis and a valve
      durability of 13 to 15 years in a population with limited life expectancy.

PMID- 7739248
TI  - Axillary artery: an alternative site of arterial cannulation for patients with
      extensive aortic and peripheral vascular disease.
AB  - The increasing number of patients with extensive aortic and peripheral vascular
      atherosclerosis or aneurysms who are undergoing cardiac operations present
      difficult decisions as to the optimal site of arterial cannulation for
      cardiopulmonary bypass. Femoral artery cannulation is the most common alternative
      to ascending aortic cannulation, but severe iliofemoral disease or the danger of
      atheroemboli caused by retrograde perfusion through an atherosclerotic or
      aneurysmal descending aorta may make this approach impossible or undesirable. We
      have used axillary artery cannulation for cardiac operations in 35 patients for
      indications including severe aortic atherosclerosis (n = 16), extensive aortic
      aneurysms (n = 11), and aortic dissection (n = 8). The cardiac operations
      performed were coronary artery bypass grafting (n = 9) aortic valve replacement
      (n = 1), aortic valve replacement and coronary artery bypass grafting (n = 5),
      repair of mitral valve periprosthetic leak (n = 1), and resection of ascending
      and/or aortic arch (n = 19). Deep hypothermia with circulatory arrest was used in
      26 patients and retrograde cerebral perfusion in 18. All patients awoke from the
      operation and no patient had a cerebrovascular accident. One patient required
      axillary artery thrombectomy and one patient had a mild ipsilateral brachial
      plexus paresis after the operation. Four patients died in the hospital. We
      conclude that axillary artery cannulation is a safe and effective means of
      providing antegrade arterial flow during cardiopulmonary bypass in patients with
      severe atherosclerotic or aneurysmal disease. This strategy may lower the
      prevalence of stroke associated with cardiopulmonary bypass in these patients.

PMID- 7739249
TI  - Microvascular dysfunction after myocardial ischemia.
AB  - Endothelium-mediated relaxation and smooth muscle function in large coronary
      arteries are resistant to prolonged global ischemia. We used a small-vessel
      myograph to test the hypothesis that small intramyocardial artery endothelium and
      smooth muscle function have greater sensitivity to ischemic injury than large
      artery endothelium and smooth muscle. Normothermic global ischemia was induced in
      15 porcine hearts. Intramyocardial arterial ring segments were assessed at 0, 30,
      60, 90, and 120 minutes of ischemia in vitro with a small-vessel myograph.
      Potassium determined smooth muscle contraction, bradykinin endothelium-mediated
      relaxation, and sodium nitroprusside direct smooth muscle relaxation. Endothelium
      mediated relaxation after 30 minutes of ischemia was similar to control (56%
      versus 66%) but was impaired at 60, 90, and 120 minutes of ischemia (32%, 11%,
      and 6%). Smooth muscle contraction was unchanged at 30 and 60 minutes compared
      with control (56 and 53 versus 63 mm Hg) but was significantly decreased at 90
      and 120 minutes (33 and 13 mm Hg). Direct smooth muscle relaxation was
      significantly decreased at 120 minutes of ischemia compared with control (58%
      versus 95%). In a previous study, epicardial coronary artery endothelium-mediated
      smooth muscle vasodilation and direct smooth muscle vasodilation were preserved
      until 160 minutes of ischemia. After 160 minutes of ischemia, endothelium
      mediated relaxation was lost and only direct smooth muscle vasodilation was
      preserved. In contrast to vasodilation, vasoconstriction was significantly
      reduced at 140 minutes of ischemia. These data indicate a greater and earlier
      adverse effect of ischemia on intramyocardial arterial endothelium-mediated
      relaxation than smooth muscle contraction or relaxation. These data support the
      hypothesis that there is an early functional endothelial cell injury associated
      with global ischemia. Relaxation that is endothelium-dependent in intramyocardial
      arteries is more sensitive to ischemic injury than in epicardial arteries. Unique
      to this study was the evaluation of small intramyocardial arteries (281 +/- 29
      microns) that are the primary sites of coronary vascular resistance.
      Microvascular endothelial dysfunction after ischemia, therefore, may contribute
      to the "no-reflow phenomenon" seen during reperfusion injury.

PMID- 7739250
TI  - Electrophysiologic effects of procainamide, mexiletine, and amiodarone on the
      transplanted heart. Experimental study.
AB  - The effects of procainamide, mexiletine, and amiodarone on automaticity,
      conduction, and refractoriness were studied in a model of heterotopic heart
      transplantation in dogs that combined an innervated heart (recipient) and a
      denervated transplanted heart (donor). After the surgical procedure, 500 mg
      procainamide (n = 13), 200 mg plus 0.1 mg/kg per minute mexiletine (n = 10), or
      150 mg amiodarone (n = 10) was administered intravenously. During a baseline
      period and after drug administration, each heart was assessed for
      atrioventricular interval; cycle length; sinoatrial conduction time;
      atrioventricular node anterograde and retrograde block points; atrioventricular
      node and ventricular antegrade effective refractory periods; PR, QRS, and QT
      intervals on electrocardiogram; systemic arterial, pulmonary arterial, central
      venous, and pulmonary capillary wedge pressures; and cardiac output. In
      recipients, procainamide reduced cardiac output, depressed sinus automaticity,
      slowed conduction time without affecting the QRS interval, and prolonged the
      nodal and ventricular refractoriness; in donor hearts, it depressed automaticity
      and prolonged nodal refractoriness, but did not modify conduction or ventricular
      refractoriness. Mexiletine only moderately depressed sinus automaticity in
      recipient hearts; it did not affect the other parameters either in recipient or
      transplanted hearts, nor did it alter the hemodynamic situation. Amiodarone
      produced hypotension, reduced cardiac output, and prolonged all the
      electrophysiologic intervals except the QRS interval in recipient hearts. These
      changes were even more pronounced in the transplanted hearts and led to extreme
      sinus bradycardia in four cases. Of these three drugs, mexiletine appears to be
      the safest should treatment for arrhythmias be necessary in transplant
      recipients.

PMID- 7739251
TI  - Modulation of alloreactivity in transplant recipients by phenotypic manipulation
      of donor endothelium.
AB  - Phenotypic manipulation of allograft endothelium to reduce immunogenicity would
      have a significant impact on transplantation. In this study we have demonstrated
      that random seeding of a heart allograft with endothelium, of host origin, not
      only promotes long-term survival, but reduces the requirement for pharmacologic
      immunosuppression. We propose that this simple technology could easily be
      extrapolated to the clinical arena where hypothermia and preservation solutions
      have allowed allografts to remain ex vivo for extended periods.

PMID- 7739252
TI  - Short-course immunosuppression after tracheal allotransplantation in dogs.
AB  - It is desirable to minimize immunosuppression after allotransplantation. We
      examined the usefulness of a short course of immunosuppression after tracheal
      allotransplantation in 35 dogs. Five animals with six-ring tracheal autografts
      served as controls (group I, n = 5). Thirty animals with six-ring tracheal
      allografts were randomly classified into five groups as follows: no
      immunosuppression (group II, n = 6), azathioprine for only 1 postoperative week
      (group III, n = 7), azathioprine for 2 postoperative weeks (group IV, n = 7),
      azathioprine for 3 postoperative weeks (group V, n = 5), and mizoribine for 3
      postoperative weeks (group VI, n = 5). All allografts in groups II through VI
      sustained rejection, but there was no difference in mononuclear cell infiltration
      of the grafts among the groups. The only grafts with long-term viability were
      those in groups I and VI, as demonstrated by graft patency and epithelialization.
      We conclude that immunosuppression with mizoribine for only a short course after
      transplantation may allow long-term viability of tracheal allografts.

PMID- 7739253
TI  - Molecular cardiomyoplasty: potential cardiac gene therapy for chronic heart
      failure.
AB  - In this study, we evaluated the feasibility of converting cardiac fibroblasts
      into skeletal muscle cells by forced expression of the MyoD gene, one of the
      basic helix-loop-helix myogenic factors. Primary cardiac fibroblasts, isolated
      from newborn rats, were infected with retrovirus-carrying sense or antisense MyoD
      gene. Ten days after infection, expression of MyoD protein was demonstrated in
      95% of cells infected with sense MyoD virus by intense nuclear immunostaining
      with a MyoD polyclonal antibody. In contrast, none of the cells infected with
      antisense MyoD virus showed staining. On withdrawal of serum, 95% of MyoD
      positive cells became elongated and, in the presence of appropriate cell density,
      fused to form multinucleated myotubes, morphologically similar to striated muscle
      cell. Expression of downstream myogenic differentiation markers, myosin heavy
      chain and myocyte-specific enhancer factor 2, in 95% of these myotubes were
      detected by intense cytoplasmic and nuclear immunostaining, respectively, with
      specific antibodies. In contrast, no detectable staining was noted in MyoD
      negative cells. Spontaneous contractile movements were noted in a few clusters of
      myotubes. In summary, cardiac fibroblasts were able to be converted into bonafide
      potentially functional skeletal myocytes as shown by definitive morphologic and
      biochemical changes. Further studies with in vivo models are needed to explore
      this unique molecular strategy to treat patients with chronic heart failure.

PMID- 7739254
TI  - Quantitative electroencephalography: a method to assess cerebral injury after
      hypothermic circulatory arrest.
AB  - Although hypothermic circulatory arrest and low-flow cardiopulmonary bypass are
      routinely used for surgical correction of congenital cardiac anomalies, use of
      long durations of arrest, often required for more complex repairs, raises serious
      concerns about cerebral safety. Searching for an intraoperative assessment that
      can reliably predict cerebral injury, we have found an excellent correlation
      between changes in quantitative electroencephalography intraoperatively and
      immediately postoperatively after prolonged hypothermic arrest, and neurologic
      and behavioral evidence of cerebral injury. After epidural placement of four
      recording electroencephalographic electrodes and baseline neurologic/behavioral
      and electroencephalographic assessment, 32 puppies were randomly assigned to one
      of four groups: hypothermic controls in which cooling to 18 degrees C was
      followed immediately by rewarming, 30 minutes of hypothermic circulatory arrest
      at 18 degrees C, 90 minutes of arrest at 18 degrees C, and 90 minutes of low-flow
      cardiopulmonary bypass at 25 ml/kg per minute at 18 degrees C. An
      electroencephalogram was recorded at baseline, after cooling, during rewarming,
      and at 2, 4, and 8 hours after the start of rewarming, as well as before the
      operation and 1 week after the operation. Postoperative neurologic and behavioral
      outcome was assessed 24 hours after cardiopulmonary bypass and daily for 1 week
      by means of a graded scale in which 0 is normal and 12 and 13 indicate severe
      neurologic injury (coma and death). Thirty animals survived the experimental
      protocol: two animals in the 90-minute hypothermic arrest group died before
      neurologic evaluation could be completed, and the remainder exhibited various
      degrees of neurologic and behavioral impairment, more severe on day 1 than on day
      6. No animal in the remaining groups had a significant neurologic deficit.
      Quantitative electroencephalographic analysis shows marked differences between
      the 90-minute arrest group and the controls in the percent
      electroencephalographic silence during rewarming and at 2 hours, and in the
      percent recovery of baseline power at 2, 4, and 8 hours. At 2 hours after the
      start of rewarming, a correlation between electroencephalographic amplitude and
      neurologic/behavioral score on day 1 was carried out, which predicts with great
      certainty (p < 0.00001) that if electroencephalographic power at this time is
      less than 500 microV2, overt neurologic injury will subsequently become apparent.
      In addition, a significant shift from higher to lower frequency in the day 6
      postoperative electroencephalogram compared with baseline occurs only in the 90
      minute arrest group.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7739255
TI  - The regional capillary distribution of retrograde blood cardioplegia in explanted
      human hearts.
AB  - Warm retrograde blood cardioplegia is frequently used for myocardial protection,
      despite experimental studies questioning the adequacy of capillary flow to the
      right ventricle and septum. The capillary distribution of retrograde blood
      cardioplegia in the human heart is unknown. Hearts from eight transplant
      recipients with the diagnosis of idiopathic or dilated cardiomyopathy were
      arrested in situ with cold blood cardioplegia and excised with the coronary sinus
      intact. Within 20 minutes of explanation, colored microspheres mixed in 37
      degrees C blood cardioplegia were administered through the coronary sinus at a
      pressure of 30 to 40 mm Hg for 2 minutes. Twelve transmural myocardial samples
      were taken horizontally at the level of midventricle and apex to determine
      regional capillary flow rates. When retrograde warm blood cardioplegia was
      administered at a rate of 0.42 +/- 0.06 ml/gm/min, the left ventricle, the
      septum, the posterior wall of the right ventricle, and the apex consistently
      received capillary flow rates in excess of their metabolic requirements. The
      capillary perfusion of anterior and lateral walls of the right ventricle was
      marginally adequate to sustain aerobic metabolism. In explanted human hearts,
      retrograde blood cardioplegia provides adequate capillary flow to the left
      ventricle, the septum, the posterior wall of the right ventricle, and the apex;
      however, capillary flow to the anterior and lateral walls of the right ventricle
      is marginal. This study delineates the tenuous balance between supply and demand
      for right ventricular protection with warm continuous retrograde blood
      cardioplegia.

PMID- 7739256
TI  - Coronary sinus ostial occlusion during retrograde delivery of cardioplegic
      solution significantly improves cardioplegic distribution and efficacy.
AB  - This study documents the gross flow characteristics and capillary distribution of
      cardioplegic solution delivered retrogradely with the coronary sinus open versus
      closed. METHODS: Five explanted human hearts from transplant recipients were used
      as experimental models. Hearts served as their own controls and received two
      doses of warm blood cardioplegic solution, each containing colored microspheres.
      The first dose was delivered through a retroperfusion catheter with the coronary
      sinus open and the second dose was delivered with the sinus occluded. Capillary
      flow was measured at twelve ventricular sites and gross flow was measured by
      examining coronary sinus regurgitation, thebesian vein drainage, and aortic
      effluent (nutrient flow). RESULTS: Coronary sinus ostial occlusion allowed for a
      significant decrease in total cardioplegic flow (1.74 +/- 0.40 ml/gm versus 1.06
      +/- 0.32 ml/gm; p < 0.05) to occur while maintaining an identical intracoronary
      sinus pressure. Ostial occlusion also resulted in an increase in the ratio of
      nutrient flow/total cardioplegic flow from 32.3% +/- 15.1% to 61.3% +/- 7.9% (p <
      0.05). A statistically significant improvement in capillary flow was found at the
      midventricular level in the posterior intraventricular septum and posterolateral
      right ventricular free wall. This improvement was also documented for the
      intraventricular septum and right ventricle at the level of the apex. CONCLUSION:
      Coronary sinus occlusion during retrograde cardioplegia significantly improves
      cardioplegic delivery to the right ventricle and posterior intraventricular
      septum. Furthermore, the technique affords a significant improvement in nutrient
      cardioplegic flow while reducing the overall volume of cardioplegic solution
      administered.

PMID- 7739257
TI  - pH strategies and cerebral energetics before and after circulatory arrest.
AB  - The pH-stat strategy compared with the alpha-stat strategy provides more rapid
      recovery of brain high-energy phosphate stores and intracellular pH after 1 hour
      of hypothermic circulatory arrest in pigs. Possible mechanisms for this
      difference are (1) improved oxygen delivery and homogeneity of brain cooling
      before deep hypothermic circulatory arrest and (2) greater cerebral blood flow
      and reduced reperfusion injury owing to extracellular acidosis during the
      rewarming phase. To identify which of these mechanisms is predominant, we studied
      49 4-week-old piglets undergoing 1 hour of deep hypothermic circulatory arrest.
      Four groups were defined according to cooling/rewarming strategy: alpha/alpha,
      alpha/pH, pH/alpha, and pH/pH. In 24 animals cerebral high-energy phosphate
      levels and intracellular pH were measured by magnetic resonance spectroscopy
      (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 5). In 25
      animals cerebral blood flow was measured by labeled microspheres, cerebral
      metabolic rate by oxygen and glucose extraction, and the redox state of
      cytochrome aa3 and hemoglobin oxygenation by near infrared spectroscopy
      (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 6).
      Cerebral blood flow was greater with pH-stat than alpha-stat during cooling
      (56.3% +/- 3.7% versus 32.9% +/- 2.1% of normothermic baseline values, p <
      0.001). Cytochrome aa3 values became more reduced during cooling with alpha-stat
      than with pH-stat (p = 0.049). Recovery of adenosine triphosphate levels in the
      initial 45 minutes of reperfusion was more rapid in group pH/pH compared with
      that in the other groups (p = 0.029). Recovery of cerebral intracellular pH in
      the initial 30 minutes was faster in group pH/pH compared with that in group
      alpha/alpha (p = 0.026). Intracellular pH became more acidic during early
      reperfusion only in group alpha/alpha, whereas it showed continuous recovery in
      the other groups. This study suggests that there are mechanisms in effect during
      both the cooling and rewarming phases before and after deep hypothermic
      circulatory arrest that could contribute to an improved cerebral outcome with pH
      stat relative to more alkaline strategies.

PMID- 7739259
TI  - Atrial natriuretic peptide replacement therapy in rats subjected to biatrial
      appendectomy.
AB  - The postoperative fluid retention found in some patients after the Cox maze
      procedure has been attributed to surgically induced loss of atrial natriuretic
      peptide. We postulated that exogenous atrial natriuretic peptide could reverse
      this antidiuresis. A rat model was used to investigate this hypothesis. In group
      I, the sham group, the atrial appendages were left intact and the animals were
      then subjected to a fluid challenge equivalent to 1% of the animal's body weight.
      In group II, after biatrial appendectomy, the animals were subjected to a fluid
      challenge similar to that in group I. Animals in group III underwent the same
      protocol as that for group II plus intravenous administration of atriopeptin III
      at varying concentrations. Urine output and plasma atrial natriuretic peptide
      levels were significantly decreased after biatrial appendectomies (p < or =
      0.01). Urine output returned to control levels after biatrial appendectomies with
      low-dose atrial natriuretic peptide infusion (0.5 pmol/min = 25.5 pg/min),
      although circulating atrial natriuretic peptide levels were lower. Urine output
      and plasma atrial natriuretic peptide levels increased with atrial natriuretic
      peptide infusions between 0.5 and 50 pmol/min. Heart rate and mean blood pressure
      did not vary significantly with atrial natriuretic peptide infusions. Thus atrial
      natriuretic peptide can be used effectively in low doses to induce a diuresis
      after biatrial appendectomies. Atrial natriuretic peptide may have clinical
      application after the Cox maze procedure.

PMID- 7739260
TI  - The effects of normothermic and hypothermic cardiopulmonary bypass on
      defibrillation energy requirements and transmyocardial impedance. Implications
      for implantable cardioverter-defibrillator implantation.
AB  - The influence of normothermic and hypothermic cardiopulmonary bypass on
      defibrillation energy requirements and transcardiac impedance is not well
      characterized. However, this relationship is of clinical importance during
      automatic defibrillator implantation done with concomitant cardiac surgery, and
      there is anecdotal information that criteria for successful implantation are
      harder to achieve after such operations. We studied the effect of controlled
      hypothermia on defibrillation energy requirements and transcardiac impedance in a
      canine model of cardiopulmonary bypass in which 26 animals underwent right atrial
      and femoral arterial cannulation, as well as continuous hemodynamic and
      intramyocardial temperature monitoring. The defibrillation energy requirements
      were evaluated at 60-minute intervals with an epicardial patch system, and
      transcardiac impedance was measured before and after the multiple inductions and
      terminations of ventricular fibrillation. In group 1 (n = 10) defibrillation
      energy requirements were evaluated immediately after initiation of
      cardiopulmonary bypass at 37 degrees C (T0), after gradual cooling to 28 degrees
      C (T1), and after rewarming to 37 degrees C (T2). Group 2 (n = 16) comprised time
      controls that were identically instrumented and studied, but maintained at 37
      degrees C throughout. Percent successful defibrillation was plotted against
      delivered energy, and the raw data fit by logistic regression. The energy at
      which 50% of shocks were successful (E50) was 3.23 +/- 0.89 joules at T0, 5.12 +/
      1.85 joules at T1, and 4.42 +/- 1.22 joules at T2 in group 1; this was not
      significantly different from the corresponding group 2 E50 values, which were
      3.11 +/- 1.39 joules, 4.95 +/- 2.47 joules, and 5.59 +/- 3.18 joules,
      respectively. Both groups demonstrated a significant increase in E50 during the
      first hour of cardiopulmonary bypass (mean increase from T0 to T1 was 1.89 joules
      in group 1 and 1.84 joules in group 2, p < 0.05). Transmyocardial impedance fell
      progressively during the group 2 experiments from 73.6 +/- 12.9 omega at the
      beginning of the T0 shock series to 61.4 +/- 8.9 omega at the end of the T2 shock
      series. A similar reduction in transmyocardial impedance was observed during the
      course of all the group 1 experiments; however, at the beginning of the T1 shock
      series impedance was significantly elevated to 77.4 +/- 12.3 omega (p < 0.05
      compared with group 2 and with end T0 in group 1). There was no relationship
      between defibrillation energy requirements and transcardiac impedance; there was
      also no correlation between either of these parameters and intramyocardial
      extracellular pH or left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7739258
TI  - Metabolic correlates of neurologic and behavioral injury after prolonged
      hypothermic circulatory arrest.
AB  - Thirty-two inbred weanling puppies were divided into four groups to study the
      effect on cerebral blood flow and metabolism of different hypothermic strategies
      for cerebral protection similar to those used during cardiac operations in
      infancy. All animals were cooled to 18 degrees C. The animals in the hypothermic
      control group were immediately rewarmed. One group underwent 30 minutes of
      hypothermic circulatory arrest at 18 degrees C; another group had 90 minutes of
      hypothermic circulatory arrest at 18 degrees C, and the final group had low-flow
      cardiopulmonary bypass (25 ml/kg per minute) at 18 degrees C for 90 minutes. All
      animals had preoperative and postoperative neurologic and behavioral evaluation
      and extensive intraoperative monitoring of cerebral blood flow, cerebral vascular
      resistance, and oxygen and glucose uptake and metabolism: quantitative
      electroencephalography was also monitored before, during and after operation, but
      those results are reported separately. Two animals in the 90-minute arrest group
      died, and all the survivors showed evidence of clinical, neurologic, and
      behavioral impairment on postoperative day 1, with residual abnormalities in all
      but one animal on day 6. In contrast, the survivors in all the other groups
      showed no significant clinical or behavioral sequelae. Cerebral metabolism was
      reduced only to 32% to 40% of baseline values at 18 degrees C in all groups,
      although systemic metabolism was only 16% of normal. Cerebral metabolism returned
      promptly to baseline in all groups during rewarming and remained at baseline
      levels throughout the 8 hours of follow-up. Cerebral blood flow showed marked
      hyperemia in the hypothermic arrest groups during rewarming but then significant
      reductions below baseline values in all groups except the controls at 2 and 4
      hours after the operation, lasting as late as 8 hours after the operation in the
      90-minute arrest group. Cerebral vascular resistance showed increases in all
      groups at 2 and 4 hours after the operation, which persisted in the 90-minute
      arrest group at 8 hours. Cerebral metabolism was maintained at baseline levels
      despite postoperative decreases in cerebral blood flow and increases in cerebral
      vascular resistance by increases in oxygen and glucose extraction. The result was
      very low sagittal sinus oxygen saturations in all groups, most marked in the 90
      minute arrest groups, which had a saturation of only 24% 8 hours after the
      operation. Our data show a severe, prolonged disturbance in cerebral blood flow
      and cerebral vascular resistance after 90 minutes of hypothermic circulatory
      arrest at 18 degrees C, which correlates with clinical evidence of cerebral
      injury.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7739261
TI  - Treatment strategies for bronchopleural fistula.
AB  - Successful management of chronic postoperative bronchopleural fistula remains a
      challenge for thoracic surgeons. Forty-two patients (33 referred from other
      institutions) were treated for major postoperative bronchopleural fistula since
      1978. Factors associated with bronchopleural fistula included right pneumonectomy
      (n = 23), left pneumonectomy (n = 8), long bronchial stump (n = 16), pneumonia (n
      = 13), radiation therapy (n = 12), stapled bronchial closure (n = 8), prolonged
      mechanical ventilation (n = 7), recurrent carcinoma (n = 6), and tuberculosis (n
      = 2). Patients had undergone an average of 3.3 surgical procedures to correct
      their bronchopleural fistulas during a mean interval of 24 months before our
      treatment. Bronchopleural fistulas were located in the right main bronchial stump
      (n = 23), left main bronchial stump (n = 8), right lobar bronchial stumps (n =
      10), and tracheobronchial anastomosis (n = 1). Thirty-five patients were treated
      by suture closure of the bronchial stump, buttressed with vascularized pedicle
      flaps of omentum (n = 19), muscle (n = 13), or pleura (n = 2). In seven cases,
      direct suture closure was not possible, and omental (n = 6) or muscle (n = 1)
      flaps were sutured over the bronchopleural fistula. Suture closure without
      pedicle coverage was performed successfully in one case. Initial repair of the
      fistula was successful in 23 of 25 patients treated with omentum, in nine of 14
      patients treated with muscle and in neither of two patients treated with pleural
      flaps. In nine patients with persistent or recurrent bronchopleural fistula after
      our initial repair, four underwent a second procedure (three successful) and five
      were managed with drainage only. The fistula was successfully closed in 11 of 12
      patients who had received high-dose radiation therapy (nine with omentum).
      Overall, successful closure of bronchopleural fistula was achieved in 36 of 42
      patients (86%). Four in-hospital deaths resulted from pneumonia and sepsis, two
      in patients with recurrent bronchopleural fistula after pleural flap closure. In
      16 patients the empyema cavity was obliterated during definitive repair of the
      fistula. The cavity resolved with drainage in four others, nine had draining
      cavities at follow-up, and one was lost to follow-up. Ten patients required a
      total of 17 Clagett procedures and one had a delayed myoplasty. Direct surgical
      repair of chronic bronchopleural fistula may be achieved in most patients after
      adequate pleural drainage by suture closure and aggressive transposition of
      vascularized pedicle flaps. Omentum is particularly effective in buttressing the
      closure of bronchopleural fistulas.

PMID- 7739262
TI  - Lobectomy--video-assisted thoracic surgery versus muscle-sparing thoracotomy. A
      randomized trial.
AB  - Video-assisted thoracic surgery has been adopted by some thoracic surgeons as the
      preferred approach over thoracotomy for many benign and malignant diseases of the
      chest. However, little concrete evidence exists to support this technique as the
      superior approach. This randomized study was carried out to define the advantages
      of video-assisted lobectomy over muscle-sparing thoracotomy and lobectomy. Sixty
      one patients with presumed clinical stage I non-small-cell lung cancer were
      entered into the study. Each patient was randomized to muscle-sparing thoracotomy
      and lobectomy or video-assisted lobectomy. Six patients were excluded from the
      study either because final pathologic results revealed nonmalignant disease (3
      patients) or because an attempted video-assisted lobectomy was converted to a
      thoracotomy. This left 30 patients in the thoracotomy group and 25 patients in
      the video-assisted group. No significant differences existed between the two
      groups in operating time, intraoperative blood loss, duration of chest tube
      drainage, or length of hospital stay. Significantly more postoperative
      complications occurred in the thoracotomy group (p < 0.5), the majority of which
      were prolonged air leaks. Return to work time was not an issue because the
      majority of the patients were either retired or not working at the time of the
      operation. Only three patients had persistent postthoracotomy pain (thoracotomy,
      n = 2; video-assisted lobectomy, n = 1). We conclude that video-assisted
      lobectomy was not associated with a significant decrease in duration of chest
      tube drainage, length of hospital stay, postthoracotomy pain, or, in this group
      of patients, a faster recovery time and return to work. Video-assisted lobectomy
      continues to expose the patient to the risk of a major pulmonary resection being
      done in an essentially closed chest. These results illustrate the need for
      critical evaluation of video-assisted thoracic surgery before the procedure is
      accepted as a superior approach based on presumed and thus far unproved
      advantages.

PMID- 7739263
TI  - Effect of treatment with the dihydropyridine-type calcium antagonist darodipine
      (PY 108-068) on the expression of calbindin D-28K immunoreactivity in the
      cerebellar cortex of aged rats.
AB  - The influence of long term treatment with the dihydropyridine-type Ca2+
      antagonist darodipine (PY 108-068) on age-dependent changes in calbindin D-28K
      immunoreactivity in the cerebellar cortex of male Wistar rats was assessed. In 12
      month-old rats used as an adult reference group, specific calbindin D-28K
      immunoreactivity was found within the cytoplasm of Purkinje neurons and their
      dendritic processes. The number of Purkinje neurons displaying calbindin D-28K
      immunoreactivity was decreased in the cerebellar cortex of aged in comparison
      with adult rats. The pattern of calbindin D-28K immunoreactivity was similar in
      the cerebellar cortex of 24-month-old rats (aged), although a significant
      decrease in the intensity of immunoreactivity was noticeable. Treatment of aged
      rats with darodipine for 6 months increased the percentage of immunoreactive
      Purkinje neurons and the intensity of calbindin D-28K immunoreactivity in the
      cytoplasm of Purkinje neurons. Calbindin D-28K is a Ca2+ binding protein probably
      involved in the modulation of Ca2+ homeostasis. The observation of a positive
      effect of darodipine treatment on calbindin D-28K immunoreactivity in the
      cerebellar cortex suggests that manipulation of dihydropyridine-type Ca2+
      channels may contribute to counter age-dependent changes of Ca2+ homeostasis.

PMID- 7739264
TI  - Alanine transport in rat liver plasma membrane vesicles during the acute-phase
      response in young and old rats.
AB  - The Na(+)-dependent transport of L-alanine into liver plasma membrane vesicles
      isolated from young, 2-month-old, and aged, 24-month-old, normal and turpentine
      treated rats, to induce an aseptic inflammatory condition and the acute-phase
      response, was studied. In old rats, alanine transport maintained the same
      features observed in young controls, being strictly Na(+)-and electrical
      potential-dependent. However, old rats showed a twofold increase in the Vmax
      value for alanine uptake compared with young controls, the affinity constant (Km)
      remaining unmodified. Four hours after turpentine treatment, the Vmax value of
      alanine transport in young rats was 2.5-fold over that observed in untreated
      controls. In contrast, old turpentine-treated rats demonstrated only slight
      increases in this value, compared to untreated old controls. In both young and
      old turpentine-treated rats, the Km values of alanine transport remained almost
      unmodified. Since dysregulation of interleukin 6 (IL-6) gene expression, a
      multifunctional cytokine that is proving to be a major contributor to the acute
      phase response, occurs with advancing age in different animal species, the
      increased alanine transport across liver plasma membrane vesicles observed in old
      "normal" rats might be related to an increased IL-6 production, inducing an acute
      phase protein synthetic activity, in these animals.

PMID- 7739266
TI  - The effect of age on the monoamines of the hypothalamus.
AB  - Measurement of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) homovanillic
      acid (HVA), 3-methoxytyramine (3-MT), noradrenaline (NA), 3-methoxy-4
      hydroxyphenyl glycol (MHPG) and serotonin (5-HT) and its main metabolite, 5
      hydroxyindol-3-acetic acid (5-HIAA) was assessed in hypothalamus and median
      eminence of aged rats. Age-related changes were not observed in the concentration
      of NA and its metabolites in median eminence. In contrast, there was a
      significant NA decrease in aged hypothalamus compared with 12 months (no
      differences were found compared with 3 months). No significant differences were
      found in DA concentration and its metabolites in hypothalamus but DA decreased
      significantly in aged median eminence compared with 12 months. The ratio 5-HIAA/5
      HT, indicative of 5-HT turnover, appeared to increase in the hypothalamus and
      median eminence of the aged rat. Morphological dissimilarities between
      hypothalamus of young and aged rats were demonstrated using serotonin
      immunocytochemistry. A degeneration of the serotoninergic system, denoted by the
      appearance of enlarged or swollen varicosities, was observed in the hypothalamus
      of the aged rat. These aberrant serotoninergic fibers may reflect the local
      degeneration of serotoninergic hypothalamic afferents during ageing. Such
      differential age-dependent alterations of the serotoninergic system might be
      responsible for at least some of the functional deficits in aged animals.

PMID- 7739267
TI  - Differential expression of the alpha- and beta-isoforms of protein kinase C in
      peripheral blood T and B cells from young and elderly adults.
AB  - The expression of alpha- and beta-isoforms of protein kinase C (PKC) was analyzed
      in the peripheral blood T and B cells from 11 elderly and young humans.
      Immunoblot analysis with isoenzyme specific antibodies showed that T cells from
      five of 11 elderly subjects exhibited selective reductions in PKC alpha which was
      < 60% of those in young subjects whereas the levels of PKC beta were comparable
      to T cells of young subjects. No age-related reductions of PKC alpha or beta were
      observed in B cells. Among individual elderly subjects, the reductions in T cell
      PKC alpha were not associated with lower levels of PKC beta thereby resulting in
      only approximately 60-70% reductions of combined PKC alpha plus PKC beta. In
      addition, the functional properties of PKC in stimulated T cells of elderly
      subjects with respect to activation/translocation were comparable to T cells of
      young subjects. These results suggest that selective alterations in PKC
      isoenzymes can occur in human T cells during aging which may not be readily
      apparent in standard enzymatic assays and may contribute to aberrancies in
      intracellular signal transduction.

PMID- 7739269
TI  - Increasing multiple myeloma mortality among the elderly: a manifestation of aging
      and differential survival.
AB  - Increasing multiple myeloma incidence and mortality among the elderly in
      industrialized nations has been attributed to associated environmental
      carcinogens. Age-specific multiple myeloma mortality rates in the United States
      from 1968 to 1989 were analyzed using the Strehler-Mildvan modification of the
      Gompertz relationship between aging and mortality. The results suggest that
      worsening environmental influences are not responsible for increasing multiple
      myeloma mortality among the elderly. Differential survival, a concept originally
      popularized by Charles Darwin, and its effect upon the surviving gene pool in an
      aging population is an alternative explanation for increasing multiple myeloma
      incidence and mortality in the elderly.

PMID- 7739268
TI  - Age-related attenuation of HSP47 heat response in fibroblasts.
AB  - The collagen-binding heat shock protein of molecular weight 47,000 (HSP47),
      resident in the endoplasmic reticulum (ER), is assumed to play a specific role as
      a molecular chaperon in the processing of procollagen molecules. The present
      investigation of age-related alteration in the HSP47 heat response in cultured
      murine and human fibroblasts revealed expression in cells with a low population
      doubling level (PDL) derived from young mice and people more inducible by heat
      treatment than those from older mice and people. On the other hand, cells with a
      high PDL showed a very low heat response in terms of HSP47 expression regardless
      of the donor age. Northern blot analysis of HSP47 m-RNA indicated that the age
      related attenuation of HSP47 expression was regulated by transcriptional
      mechanisms. Furthermore, immunofluorescent analysis using a monoclonal antibody
      against the carboxylterminal propeptide of type I procollagen revealed far
      greater retention of procollagen molecules in the ER lumen of cells from old
      persons than in those from young persons. This was particularly prominent in heat
      treated cells from old persons, indicating the possibility that the observed
      decrease in HSP47 heat response might cause blockage of procollagen transport to
      the Golgi and therefore secretion.

PMID- 7739265
TI  - Decreases in macrophage mediated antitumor activity with aging.
AB  - We have demonstrated that immunotherapy of young (6-10 weeks old), and aged,
      (greater than 24 months old), tumor bearing mice with biological response
      modifiers enhanced survival and inhibited tumor growth, while treatment of aged
      mice had little or no effect. We hypothesized that the antitumor activity in
      young mice was principally mediated by activated macrophages (M phi) and
      predicted that the change in aged mice was caused by an intrinsic M phi defect
      which develops with advancing age. To directly test our hypothesis, we examined
      the antitumor activity of resident peritoneal M phi, purified and activated in
      vitro with IFN gamma plus LPS. Paralleling the results seen in vivo, M phi from
      aged mice exhibited reduced antitumor activity in comparison with M phi from
      younger mice. Moreover, there was reduced capacity of in vitro activated M phi
      from aged mice to produce TNF, IL-1 and nitric oxide, which are critical
      monokines and effector molecules that have been established to either directly
      inhibit tumor growth or cause tumor cell destruction. These studies establish
      that peritoneal M phi from aged mice have an intrinsic defect which prevents them
      from fully expressing their antitumor potential.

PMID- 7739270
TI  - Predicting agency participation in interorganizational networks providing
      community care.
AB  - In response to health care reform, health care providers have begun to develop
      interorganizational networks. At present, however, relatively little is known
      about factors facilitating participation in networks. To this end, organizational
      characteristics and views were obtained from key informants from both "Lead" and
      "Affiliate" Agencies participating in the networks for the Living-at-Home Program
      (LAHP) Demonstration (N = 131) using an Organizational Change Survey. Logistic
      regression analysis was used to examine factors related to network member
      agencies' participation. Significant relationships were found between decreased
      participation and lack of agreement between network agencies regarding
      expectations (P = 0.02), membership in a network with a Medical Lead Agency (P <
      0.01), and Lead Agency inexperience (P < 0.01). Agencies with lower ratings of
      the impact that LAHP had on their community were more likely to decrease their
      participation (P = 0.01). The number of unoccupied nursing home beds in the
      community was positively and significantly related to decreased participation (P
      < 0.001). These results suggest that leadership skills of the Lead Agency, and in
      particular, experience, may be among the chief requirements for the creation and
      development of successful networks, and confirm that inexperienced Lead Agencies
      may face an uphill battle in terms of recruiting and maintaining network members.

PMID- 7739272
TI  - Profiling physician practice patterns using diagnostic episode clusters.
AB  - Health plans and providers need to profile current practice patterns to
      understand better the resources used in managing medical conditions. A profiling
      system is presented that groups International Classification of Diseases (ICD-9
      CM) codes into 125 diagnostic clusters based on clinical homogeneity with respect
      to physician treatment response. For each diagnostic cluster, diagnostic episode
      clusters (DECs) are formulated. A DEC links all services incurred in treating a
      patient's medical condition within a specific period of time. Each DEC is marked
      with a severity-of-illness, comorbidity, and age indicator. To test the validity
      of the diagnostic cluster methodology, claims were analyzed from a preferred
      provider organization (PPO) and an independent practice association (IPA). PPO
      and IPA DEC charges and utilization were compared with t-tests. Physician
      practice patterns differed based on patient severity of illness, comorbidities,
      and age. Both PPO and IPA physicians delivered significantly more resources to
      patients in higher severity-of-illness categories. PPO physicians generally
      treated older patients with more resources than younger patients. Patient age did
      not have the same impact on IPA physicians' practice patterns. IPA physicians'
      average treatment pattern was about 22% less expensive than that of PPO
      physicians. IPA physicians decreased average expenses by reducing hospital days
      by about 73% (P < 0.01) and hospital outpatient visits by about 89% (P < 0.01)
      compared to the rates of PPO physicians. Ambulatory services among IPA physicians
      were not significantly higher than rates for PPO physicians. The DEC methodology
      is a valid approach for profiling patterns of treatment. The style of medicine in
      the IPA was less hospital intensive and, consequently, less expensive than that
      practiced by PPO physicians. PPO physicians also had greater practice pattern
      variations than IPA physicians.

PMID- 7739271
TI  - Evaluation of screening criteria for adverse events in medical patients.
AB  - The goals of this study were to evaluate the sensitivity and specificity of 15
      screening criteria for adverse events, preventable adverse events, and severe
      adverse events in medical patients, and to evaluate combinations of these
      criteria, including those available through hospital billing data, to determine
      whether a small subset of generic screens might efficiently identify adverse
      events. The authors studied 3,137 consecutive admissions to a medical service
      over a 4-month period at an urban tertiary care hospital. Chart reviews were
      performed after discharge by reviewers blinded to the eventual determination of
      presence of an adverse event. Judgments regarding presence, severity, and
      preventability of adverse events were made using guided implicit reviews by
      physicians. Of all admissions, 341 (11%) were judged to include an adverse event,
      of which 274 were severe and 145 were preventable. Sensitivity and specificity of
      individual screens varied widely, with prior hospitalization the most sensitive
      (68%) but least specific (56%). Death was specific (97%) but not sensitive (9%);
      readmission was intermediate (sensitivity 28%, specificity 80%). In analyses
      using severe and preventable adverse events as the outcome, results were
      generally similar. Combinations of screens also were compared, including some
      using only screens available through billing data; the most sensitive billing
      strategy detected just 47% of adverse events, but cost only $3 per admission
      reviewed and $57 per adverse event, versus $13 per admission and $116 per adverse
      event for a strategy in which all records were reviewed. It is concluded that no
      small subset of screens identified a high percentage of adverse events. Using
      screens available through billing data, although insensitive, would be much less
      costly.

PMID- 7739273
TI  - Are prescribed and over-the-counter medicines economic substitutes? A study of
      the effects of health insurance on medicine choices by the elderly.
AB  - This article examines the influence of insurance coverage on the selection of
      over-the-counter (OTC) and prescribed (Rx) medicines in treating less serious
      health problems. Because health insurance policies typically provide no coverage
      for OTC products, a low list price for an OTC may exceed the after-insurance
      expense associated with a much higher-priced prescription. Under these
      circumstances, rational individuals with insurance will choose prescribed
      medicines even if OTCs are equally effective. Ten common health problems
      typically managed with either Rx or OTC medicines were selected for analysis. The
      study population consists of elderly Pennsylvanians surveyed during 1990 who
      reported suffering one or more of these conditions (N = 2,962). Multivariate
      analysis confirmed that 1) people with prescription coverage are significantly
      more likely to medicate a given problem than are those without it; and 2) given
      the decision to medicate, the presence of insurance significantly increases the
      level of Rx use and significantly reduces the level of OTC use. As expected, the
      effect was strongest among people with the most complete prescription insurance
      coverage. The article discusses the implications of these findings in the context
      of national health reform and Food and Drug Administration policy regarding Rx-to
      OTC switches.

PMID- 7739275
TI  - Patterns of health services utilization and mammography use among women aged 50
      to 59 years in the Quebec Medicare system.
AB  - Many studies have identified physicians' recommendation as the single most
      important predictor of mammography use. Health services utilization is a complex
      phenomenon, and the contribution of the different dimensions of health services
      utilization on mammography use is underresearched. This study examines the
      specific contribution of health services utilization variables in a multivariate
      model of the recency of mammography use for women aged 50 to 59 years. Subjects
      were respondents of the 1987 Quebec Health Survey. Survey data were then linked
      on an individual basis to the respondent's records of Medicare physicians' claims
      for health care services for the 3 years before the survey. This unique data set
      enabled the inclusion of sociodemographic variables, risk factors, health status,
      healthy lifestyles, and women's patterns of utilization of general and
      gynecologic health care services. Multivariate predictors of the recency of
      mammography are: having an education higher than high school, working outside
      home, not living in a remote area, suffering from benign breast disease, and not
      perceiving one's own health as good. The volume of general and gynecologic
      medical care is associated with the recency of mammography in independent
      logistic models that include women's predisposing, enabling, and need factors.
      This study shows that even in a universal third-party payer health care system,
      physicians are missing opportunities to promote breast cancer screening.

PMID- 7739274
TI  - The association of hospital volumes of percutaneous transluminal coronary
      angioplasty with adverse outcomes, length of stay, and charges in California.
AB  - The objective of this study was to examine whether hospital volumes of
      percutaneous transluminal coronary angioplasty (PTCA) are associated with adverse
      outcomes (coronary artery bypass graft surgery after PTCA and/or in-hospital
      mortality), post-PTCA length of stay (LOS), and hospital charges. Discharge data
      for 24,856 patients undergoing PTCA in 1989 from 110 California hospitals were
      analyzed. Regression analysis was used to adjust patient discharge data for risk
      factors. Actual and predicted adverse outcomes, LOS, and charges were compared
      for hospital volume categories (using 95% confidence intervals). Rates of adverse
      outcomes were significantly higher than expected in low-volume hospitals (< 201
      PTCAs) and significantly lower than expected in high-volume hospitals (> 400
      PTCAs). The results were similar for LOS and charges, although the results for
      charges were less conclusive. The associations of volumes and outcomes were
      generally consistent for both unadjusted and adjusted analyses, for patients with
      and without principal diagnoses of acute myocardial infarction, and using
      different methods and functional forms. Given this association between hospital
      volumes of PTCA and outcomes, future research should assess the underlying causes
      of this association and whether limiting the use of low-volume facilities would
      improve outcomes.

PMID- 7739276
TI  - Estimating the hospital-wide cost differentials warranted for teaching hospitals.
      An alternative to regression approaches.
AB  - Under Medicare's Prospective Payment System, teaching hospitals receive
      additional reimbursements, vis-a-vis nonteaching hospitals, for both "direct"
      teaching expenses and for "indirect" expenses. They totaled $3.1 billion in
      fiscal year 1989. The authors propose and illustrate a non-regression-based,
      nonparametric method for viewing the total hospital-wide reimbursement
      differential warranted for teaching hospitals, a method utilizing a peer grouping
      of like hospitals to estimate two different "best practices" cost frontiers. The
      hospital's efficiently delivered cost to meet all of the hospital's actual
      service outputs, including its teaching mission, and delivered level of quality
      of care, is compared to the corresponding cost when only the teaching mission is
      excluded. The difference in these costs for a particular hospital can be used to
      estimate a suggested lump sum Medicare reimbursement add-on, in recognition of
      the hospital's teaching mission. The approach is illustrated using a subset of
      the Health Care Financing Administration's 1988 hospital data set, with
      comparisons of actual and suggested reimbursements provided.

PMID- 7739277
TI  - The adolescent child health and illness profile. A population-based measure of
      health.
AB  - This study was designed to test the reliability and validity of an instrument to
      assess adolescent health status. Reliability and validity were examined by
      administration to adolescents (ages 11-17 years) in eight schools in two urban
      areas, one area in Appalachia, and one area in the rural South. Integrity of the
      domains and subdomains and construct validity were tested in all areas.
      Test/retest stability, criterion validity, and convergent and discriminant
      validity were tested in the two urban areas. Iterative testing has resulted in
      the final form of the CHIP-AE (Child Health and Illness Profile-Adolescent
      Edition) having 6 domains with 20 subdomains. The domains are Discomfort,
      Disorders, Satisfaction with Health, Achievement (of age-appropriate social
      roles), Risks, and Resilience. Tested aspects of reliability and validity have
      achieved acceptable levels for all retained subdomains. The CHIP-AE in its
      current form is suitable for assessing the health status of populations and
      subpopulations of adolescents. Evidence from test-retest stability analyses
      suggests that the CHIP-AE also can be used to assess changes occurring over time
      or in response to health services interventions targeted at groups of
      adolescents.

PMID- 7739278
TI  - [C-reactive protein in differential diagnosis of primary thrombocytosis].
AB  - BACKGROUND: The most potent stimulator for the hepatic synthesis of C-reactive
      protein is the interleukin-6. Also interleukin-6 is endowed with thrombopoietic
      activity, and its seric levels increases in most of secondary thrombocytosis
      whereas they remain normal in chronic myeloproliferative diseases or primary
      thrombocytosis. The aims of the study were verify the ability of quantitation of
      serum C-reactive protein in the differential diagnosis of primary thrombocytosis.
      METHODS: Serum samples from 89 patients with thrombocytosis (> 400 x 10(9)/1) and
      54 normal controls were assayed for C-reactive protein. Patients with
      thrombocytosis were classified in primary thrombocytosis with 27 patients
      (chronic myeloproliferative disease with thrombocytosis) and secondary
      thrombocytosis (62 cases). RESULTS: The mean C-reactive protein serum levels
      observed in the 27 patients with primary thrombocytosis were 13 +/- 10 mg/l,
      superior to normal controls (7 +/- 5 mg/l; p < 0.01). In the secondary
      thrombocytosis group, C-reactive protein serum levels reached a mean value of 59
      +/- 34 mg/l, clearly superior to control group and the primary thrombocytosis
      group (p < 0.0001). No patients in primary thrombocytosis group reached a C
      reactive protein value > 40 mg/l, versus 65% of patients in secondary
      thrombocytosis group. A normal value occurred in 67% cases of primary
      thrombocytosis group, but also in 17% cases of secondary thrombocytosis group.
      CONCLUSIONS: Quantitation of C-reactive protein could thus prove useful in the
      differential diagnosis between primary and secondary thrombocytosis.

PMID- 7739279
TI  - [Current trends in the use of statistics in medicine. A study of original
      articles published in the Medicina Clinica (1991-1992)].
AB  - BACKGROUND: In recent years there has been a notable increase in the use of
      statistical techniques in biomedical journals. Furthermore, the complexity of
      statistical analysis has increased because of data processing. In this study
      statistical accessibility is quantified and the types of statistical analysis
      performed in all the articles published under the section of original articles in
      the journal Medicina Clinica from 1991 to 1992 (volumes 96 to 99). METHODS: One
      reviewer analyzed a total of 264 original articles. The statistical analyses were
      classified according to a list with 18 categories. The quantification of
      accessibility was obtained from the order of the 18 categories with bivariate
      statistics (up to simple regression), being used as the reference threshold.
      Intrareviewer concordance was 97%. RESULTS: Eighty-one percent of the 264
      originals used categories of statistical analysis beyond that of descriptive
      statistics (inferential methods). The originals used bivariate tables (49.2%) and
      t and z tests (33.3%) most frequently. In 1992 the use of variance analysis and
      survival analysis increased notably (from 12.8% to 33.8% and 7.2% to 18.7%,
      respectively). More complex statistical techniques that models of simple
      regression (threshold reference) were used in 38.3% of the originals (31.2% in
      1991 and 44.6% in 1992). CONCLUSIONS: The use of inferential statistics and the
      complexity of statistical analysis has increased suggesting a lower statistical
      accessibility in the originals of Medicina Clinica. The categories of variance
      analysis and survival analysis were those in which the greatest increase was
      observed in 1992 and were responsible for the increase in the complexity of 20%
      of the originals.

PMID- 7739281
TI  - [The significance of C-reactive protein evaluation].

PMID- 7739280
TI  - [Evaluation of the use of statistical techniques in original articles published
      in the Medicina Clinica during 3 decades (1962-1992)].
AB  - BACKGROUND: The incorrect use of statistical techniques in medical articles may
      seriously compromise the validity of conclusions. This finding otherwise is
      relatively common. METHODS: A total of 84 original articles published in Medicina
      Clinica between 1962 and 1992 were reviewed with the aim of assessing the use and
      appropriateness of statistical techniques. The use of statistics, the quality of
      the analyses performed, and the inaccuracy of the statistical techniques used
      were evaluated. We also classified the statistical techniques most commonly used
      throughout the study period. RESULTS: There was a marked increase in the use of
      statistical analyses, from 8.3% in 1962 to 83.3% in 1992. It should be noted that
      a substantial part of this increase has been due to the use of inferential tests,
      which accounted up to 70% in the sample of articles published in 1992. This
      finding, however, was associated with an increase in the number of incorrect
      analyses. The most common statistical errors included assumption of normal
      distribution of data (with no mention of the test used to confirm this fact),
      mistake between standard deviation and standard error of the mean, inadequate
      inferences on the basis of the sample size, inappropriate use of the Student's t
      test, chi-square test, nonparametric tests or multivariate analyses as well as
      misunderstanding of linear regression and correlation. CONCLUSIONS: High
      standards in scientific research have been accompanied by a significant increase
      in the number of clinical studies with statistical analysis of data. However,
      this apparently favorable situation has been associated with an increase in the
      number of inaccurate analyses. It has been found that sophisticated statistical
      tests are rarely used in articles published in Medicina Clinica.

PMID- 7739282
TI  - [Statistics in the Medicina Clinica].

PMID- 7739283
TI  - [Cytokines and nitric oxide in streptococcal toxic shock syndrome].
AB  - The plasma levels of endotoxin, tumor necrosis factor- alpha (TNF-alpha),
      interleukin -1 beta (IL-beta), IL-6, IL-8 and the nitrites and nitrates (NO2-/NO3
      ) as stable metabolites of nitric oxide (NO) were studied in the plasma of 2
      patients with the streptococci toxic shock syndrome (STSS) associated to
      necrotizing fasciitis. A plasma profile of inflammatory mediators with high
      cytokine concentrations and NO2-/NO3- were observed with circulating endotoxin
      not being detected in plasma. The first patient died of fulminant refractory
      shock while the second survived following subacute evolution. The mediators
      profile, which was much higher in the first case, coincided with clinical
      severity. These data suggest that the cytokines and NO may have a role in the
      physiopathology of STSS and the severity of it is related to the levels of these
      mediators in the acute phase.

PMID- 7739284
TI  - [From quality control to total quality].

PMID- 7739285
TI  - [Anti-HIV therapy (1987-1994): from nothing to confusion].

PMID- 7739286
TI  - [Role of oxidative stress in gene expression: myocardial and cerebral ischemia,
      cancer and other diseases].

PMID- 7739287
TI  - [Considerations on hormone replacement therapy].

PMID- 7739288
TI  - [Urinothorax: a rare cause of pleural effusion].

PMID- 7739289
TI  - [Cerebral ischemia as initial manifestation of infectious endocarditis].

PMID- 7739290
TI  - [Intraparenchymatous hematoma simulating a transitory ischemic stroke].

PMID- 7739291
TI  - [Invasion of the right atrium by hepatocarcinoma with the appearance of a right
      to-left shunt].

PMID- 7739292
TI  - The chemical and biological properties of hypericin--a compound with a broad
      spectrum of biological activities.

PMID- 7739293
TI  - Inhibitors of phospholipid intracellular signaling as antiproliferative agents.
AB  - The improved understanding of oncogenesis and the involvement of oncogenes and
      tumor suppressor genes, has led to a rational approach of specific target
      directed anti-cancer drug development. Cancer genes have been found to be
      important not only in the control of cell proliferation but also in the mediation
      of processes such as drug resistance, metastasis, neo-vascularization
      (angiogenesis), and apoptosis. These are all important targets in their own right
      and the development of drugs against specific "upstream" targets in oncogenic or
      growth factor signal transduction cascades it may be possible to inhibit multiple
      "downstream" targets. Ultimately, to test the hypothesis that signaling pathways
      offer good targets for anticancer drug development will take several years of
      careful clinical study and we cannot say at this time whether the approach will
      work. There are a small number of compounds in the early stages of clinical
      development as anticancer agents that may act by inhibiting growth factor
      signaling pathways. In all cases the activity of the compounds on intracellular
      signaling pathways was discovered after their identification as antiproliferative
      agents. There are also compounds in preclinical development that have been
      specifically developed as inhibitors of growth factor signaling, although their
      selectivity for tumor cells compared to normal tissue remains to be investigated
      fully in appropriate animal tumor models. It is possible that a single
      antisignaling drug by itself may not have the power to completely inhibit tumor
      growth and a combination of drugs may be needed. It may also take a combination
      of drugs to prevent the emergence of resistance. Clearly there are several
      challenges to developing this new class of anticancer drugs, and there will
      undoubtedly be others that must be faced.

PMID- 7739294
TI  - The case books of Dr. John Snow.

PMID- 7739295
TI  - The British Army and the problem of venereal disease in France and Egypt during
      the First World War.

PMID- 7739296
TI  - A Linnaean thesis concerning Contagium vivum: the 'Exanthemata viva' of John
      Nyander and its place in contemporary thought.

PMID- 7739298
TI  - The dissenting tradition in English medicine of the seventeenth and eighteenth
      centuries.

PMID- 7739297
TI  - Blackley and the development of hay fever as a disease of civilization in the
      nineteenth century.

PMID- 7739299
TI  - Elizabeth Gaskell and mesmerism: an unpublished letter.

PMID- 7739300
TI  - Prison cell to pixel.

PMID- 7739301
TI  - Harnessing the profit motive.

PMID- 7739302
TI  - Why do patients with emphysema lose weight?

PMID- 7739303
TI  - From fluoroquinolones to 2-pyridones.

PMID- 7739304
TI  - The age of dehydroepiandrosterone.

PMID- 7739305
TI  - Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme.
AB  - The use of angiotensin-converting-enzyme (ACE) inhibitors has been associated
      with increased insulin sensitivity in diabetic patients. Although such an effect
      could be beneficial in the treatment of hypertension or congestive heart failure
      in diabetic patients, it might also precipitate severe hypoglycaemia. To test
      this hypothesis we carried out a nested case-control study, using data in the
      Dutch PHARMO system (1986-92), among diabetic patients treated with insulin or
      with oral antidiabetic drugs, who were admitted to hospital with hypoglycaemia.
      We identified 94 patients who had been admitted with hypoglycaemia and selected
      654 controls from the same cohort. With adjustment for a wide range of potential
      confounding factors, hypoglycaemia was significantly associated with current use
      of ACE inhibitors (odds ratio 2.8 [95% CI 1.4-5.7]). Both among users of insulin
      and among users of oral antidiabetic drugs, use of ACE inhibitors was
      significantly associated with an increased risk of hospital admission for
      hypoglycaemia (2.8 [1.2-6.4] and 4.1 [1.4-12.2], respectively). Although ACE
      inhibitors have several advantages over other antihypertensive drugs in diabetes,
      the risk of hypoglycaemia should be taken into account. Further investigation of
      the mechanism is needed since as many as 13.8% of all hospital admissions for
      hypoglycaemia might be attributable to use of ACE inhibitors.

PMID- 7739306
TI  - Treatment of keloid sternotomy scars with 585 nm flashlamp-pumped pulsed-dye
      laser.
AB  - Despite increasing knowledge of wound healing and collagen metabolism,
      hypertrophic scars and keloid scars are difficult to eradicate. Median sternotomy
      scars are often hypertrophic or keloidal. We treated them with a 585 nm flashlamp
      pumped pulsed-dye laser, which selectively injures cutaneous microvessels without
      inducing scars. 16 adult patients with hypertrophic or keloidal median sternotomy
      scars after heart surgery received two treatments to one half of their previously
      untreated scars every 6-8 weeks and were reviewed at 6 months. Symptoms and
      clinical, histological, photographic, and surface texture assessments were
      obtained for treated and untreated areas of scar and evaluated independently by
      two observers blind to the treatment and by digital image analysis of skin
      surface casts. There was a significant improvement in erythema, scar height, skin
      surface texture, and pruritus in laser-treated scar areas; this improvement
      persisted for at least 6 months.

PMID- 7739307
TI  - Randomised comparison of subcutaneous heparin, intravenous heparin, and aspirin
      in unstable angina. Studio Epoorine Sottocutanea nell'Angina Instobile (SESAIR)
      Refrattorie Group.
AB  - Intravenous heparin has been used in the control of myocardial ischaemia in
      patients with unstable angina. We set out to assess the efficacy of subcutaneous
      heparin in reducing myocardial ischaemia in patients with unstable angina. 343 of
      399 patients with unstable angina were monitored for 24 h and 108 were refractory
      to conventional antianginal treatment and were entered into a randomised
      multicentre trial. 37 patients were assigned to heparin infusion (partial
      thromboplastin time 1.5-2 times baseline), 35 to subcutaneous heparin (adjusted
      dose with partial thromboplastin time 1.5-2 times baseline), and 36 to aspirin
      (325 mg daily). All had additional conventional antianginal therapy. After the
      run-in patients were monitored for 3 days. The primary endpoint was reduced
      myocardial ischaemia assessed by the number of anginal attacks, silent ischaemic
      episodes, and duration of ischaemia per day. At 1 week and 1 month we accounted
      for anginal attacks and other clinical events (myocardial infarction,
      revascularisation procedures, and death). Aspirin did not significantly affect
      the incidence of myocardial ischaemia. On the first 3 days, infused and
      subcutaneous heparin significantly decreased the frequency of angina (on average
      by 91% and 86%, respectively), episodes of silent ischaemia (by 56% and 46%), and
      the overall duration of ischaemia (66% and 61%) versus run-in day and aspirin (p
      < 0.001 for all variables). The favourable effects of heparin therapy remained
      evident during follow-up. Only minor bleeding complications occurred.
      Subcutaneous heparin is effective in the control of myocardial ischaemia in
      patients with unstable angina.

PMID- 7739308
TI  - Molecular epidemiology of an outbreak of infection with hepatitis C virus in
      recipients of anti-D immunoglobulin.
AB  - In a retrospective investigation of possible transmission of hepatitis C virus
      (HCV) by anti-rhesus D immunoglobulin (anti-D) in 1977, we compared variants
      infecting anti-D recipients in Ireland of one of the implicated batches with
      those of epidemiologically unrelated HCV-infected individuals. All 100 of the
      recipients of the batch investigated to date were infected with a single genotype
      (type 1), consistent with a single-source outbreak, whereas a wider range of
      genotypes (1, 2, and 3) were found in anti-HCV positive individuals from Ireland
      infected by different routes. Nucleotide sequences from a 222 base fragment from
      the NS-5 region of the genome amplified from stored aliquots of the implicated
      batch closely matched those detected in anti-D recipients 17 years after the
      transmission event. This study shows the value of molecular epidemiological
      techniques for identifying distant sources of infection, and for the
      epidemiological investigation of the current distribution and transmission of HCV
      in different populations.

PMID- 7739309
TI  - Association of Glu 27 beta 2-adrenoceptor polymorphism with lower airway
      reactivity in asthmatic subjects.
AB  - Cells expressing the Glu 27 beta 2-adrenoceptor polymorphism show attenuated down
      regulation of the receptor after long-term exposure to agonist. We studied beta 2
      adrenoceptor genotype for the Gln/Glu 27 polymorphism and airway reactivity in 65
      patients with mild to moderate asthma. Glu 27 homozygotes had a four-fold higher
      geometric mean methacholine PD20 (provocative dose) than individuals who were
      homozygous for the wild-type (Gln 27) form of the receptor; heterozygotes had an
      intermediate value (3.23, 0.86, 1.96 mumol, respectively). These data suggest
      that beta 2-adrenoceptor genotype is important in the establishment of the
      asthmatic phenotype.

PMID- 7739310
TI  - Asthma.

PMID- 7739311
TI  - Does counterperfusion supersaturation cause gas cysts in pneumatosis cystoides
      coli, and can breathing heliox reduce them?
AB  - The pathogenesis of pneumatosis cystoides coli remains obscure in the absence of
      an explanation for why pockets of gas should form in the first place and why they
      should be maintained in the wall and mesentery of the colon. Counterperfusion
      supersaturation could explain the formation and location of the gas cysts, which
      occur mostly near blood vessels on the mesenteric border of the colon, and the
      absence of methane gas in them. The hypothesis can be tested by treating patients
      with pneumatosis cystoides coli with heliox.

PMID- 7739313
TI  - Medical research charities squeezed.

PMID- 7739312
TI  - South Africa: a fragile miracle.

PMID- 7739314
TI  - Research into topical microbicides against STDs.

PMID- 7739315
TI  - Mesothelioma.

PMID- 7739316
TI  - Mesothelioma.

PMID- 7739317
TI  - Fluconazole prophylaxis for high-risk liver transplant recipients.

PMID- 7739318
TI  - Bone-marrow transplantation for leukaemia.

PMID- 7739319
TI  - Symptomatic myopathy in hepatitis C infection without interferon therapy.

PMID- 7739320
TI  - Early-onset coagulase-negative staphylococcal sepsis in preterm neonate. National
      Institute of Child Health and Human Development (NICHD) Neonatal Research
      Network.

PMID- 7739321
TI  - Vitamin D receptor genotypes and bone mineral density.

PMID- 7739322
TI  - Demarcation of ulcerative colitis.

PMID- 7739323
TI  - Post World War II stress syndrome.

PMID- 7739324
TI  - Euthanasia.

PMID- 7739325
TI  - Primary health care projects and social development.

PMID- 7739327
TI  - A physician's eyewitness report in Iraq.

PMID- 7739326
TI  - Transmission of HIV in women.

PMID- 7739328
TI  - Hyponatraemia after rehydration with sports drink.

PMID- 7739329
TI  - Viscous hearing loss.

PMID- 7739330
TI  - Early diagnosis of Duchenne muscular dystrophy.

PMID- 7739331
TI  - Antibiotics in acute bronchitis.

PMID- 7739332
TI  - Antibiotics in acute bronchitis.

PMID- 7739333
TI  - Antibiotics in acute bronchitis.

PMID- 7739334
TI  - Vitamin K prophylaxis in high-dose chemotherapy.

PMID- 7739335
TI  - Uveitis associated with post-transfusional human T-lymphotropic virus type 1.

PMID- 7739336
TI  - Altered actin binding with myosin mutation in hypertrophic cardiomyopathy and
      sudden death.

PMID- 7739337
TI  - Virus infection and clotting factor concentrates.

PMID- 7739338
TI  - Tacrine.

PMID- 7739339
TI  - Virus infection and clotting factor concentrates.

PMID- 7739340
TI  - Low frequency of myelodysplasia after autologous bone marrow transplantation.

PMID- 7739341
TI  - Anaphylaxis after hepatitis B vaccination.

PMID- 7739342
TI  - Coexistence of Vibrio cholerae O1 and O139 Bengal in plankton in Bangladesh.

PMID- 7739343
TI  - The hyperstethoscope syndrome.

PMID- 7739344
TI  - The hyperstethoscope syndrome.

PMID- 7739345
TI  - The hyperstethoscope syndrome.

PMID- 7739346
TI  - The hyperstethoscope syndrome.

PMID- 7739347
TI  - Opioid receptor interaction and adenylyl cyclase inhibition of dihydroetorphine:
      direct comparison with etorphine.
AB  - To find out the reason of weak addiction property of dihydroetorphine, we
      compared the affinities of dihydroetorphine to the type selective opioid receptor
      and inhibition effect on the adenylyl cyclase activity with those of etorphine.
      Dihydroetorphine and etorphine have almost the same binding affinities to all
      types (mu, delta, and kappa) of opioid receptors and antagonist binding sites,
      and have similar inhibition activities to forskolin stimulated adenylyl cyclase.
      However, dihydroetorphine showed significantly smaller value of DTNB-index
      compared with that of etorphine. This differentiation may explain partly the high
      analgesic with low dependence properties of dihydroetorphine.

PMID- 7739348
TI  - Endothelium-derived relaxing factors in the kidney of spontaneously hypertensive
      rats.
AB  - Acetylcholine (ACh)-induced vasodilation is mainly due to endothelium-derived
      nitric oxide (EDNO) and hyperpolarizing factor (EDHF). To explore the mechanisms
      underlying attenuated endothelium-dependent vasodilation in hypertensive
      arteries, we measured the EDNO released from isolated kidneys of spontaneously
      hypertensive rats (SHR) using a sensitive chemiluminescence assay system of NO.
      ACh-induced renal vasodilation was significantly smaller in SHR than in the
      normotensive control, Wistar-Kyoto rats (WKY). However, ACh-induced NO release
      did not differ between SHR and WKY (10(-7) M: SHR +37 +/- 2 [SE] vs. WKY +32 +/-
      4 fmol/min/g kidney). Perfusion with a 20 mEq/L high-K+ buffer, which is reported
      to inhibit action of EDHF, significantly reduced ACh-induced vasorelaxation in
      WKY but not in SHR, resulting in identical renal perfusion pressure in SHR and
      wKY under these conditions. These results indicate that attenuated ACh-induced
      vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF rather
      than that in EDNO.

PMID- 7739350
TI  - Routes of administration and effect of carbidopa pretreatment on 6-[18F]fluoro-L
      dopa/PET scans in non-human primates.
AB  - In 6-[18F]fluoro-L-dopa (Fdopa)/positron emission tomography (PET) studies,
      carbidopa pretreatment increases the Fdopa bioavailability to the brain and
      enhances the intensity of striatal PET images. Different PET research teams have
      used various carbidopa doses and routes of administration in non-human primate
      studies. The purpose of this study was to examine the plasma profiles of
      carbidopa and the effect of the route of administration of carbidopa on a
      Fdopa/PET scan. Cynomolgus monkeys were given carbidopa either orally (5 mg/kg),
      intraperitoneally (2.5 and 5 mg/kg) or intravenously (5 mg/kg) 60-90 min prior to
      the Fdopa injection. Carbidopa-treated monkeys were compared to monkeys without
      carbidopa treatment. No carbidopa was detected in the plasma samples when it was
      given orally, possibly due to poor absorption in the gastrointestinal tract. In
      addition, the striatal and cortical activities were not statistically different
      from those of the untreated monkeys, indicating that little or no inhibition of
      the peripheral decarboxylation of Fdopa by carbidopa had taken place. When
      carbidopa was given intraperitoneally at a dose of 2.5 and 5 mg/kg and
      intravenously at 5 mg/kg, plasma carbidopa concentrations at the time of Fdopa
      injection were 0.95 +/- 0.26, 2.22 +/- 0.23 and 2.79 +/- 0.26 micrograms/ml,
      respectively. Because of inhibition of peripheral decarboxylation of Fdopa by
      carbidopa, more Fdopa was available for transport into the brain and as a result,
      both the striatal and cortical activities were significantly higher than those of
      the untreated monkeys. Carbidopa administration had no effect on either the
      striatal-to-cortical activity ratio or the striatum uptake value.

PMID- 7739349
TI  - Structure, oxidant activity, and cardiovascular mechanisms of human
      ceruloplasmin.
AB  - Ceruloplasmin is the principal carrier of copper in human plasma. It is an
      abundant protein that participates in the acute phase reaction to stress, but its
      physiological function(s) is unknown. An antioxidant activity of ceruloplasmin
      has been described, but recent evidence suggests that the protein may also
      exhibit potent pro-oxidant activity and cause oxidative modification of low
      density lipoprotein (LDL). The pro-oxidant activity is highly dependent on the
      structure of the protein; removal of a single one of the seven integral copper
      atoms, or a specific proteolytic cleavage event, completely suppresses LDL
      oxidation. This newly described pro-oxidant activity may help to explain
      epidemiological studies indicating that ceruloplasmin is an independent risk
      factor for cardiovascular disease.

PMID- 7739351
TI  - Retinoic acid-induced stress protein synthesis in the mouse.
AB  - We have previously demonstrated that stress proteins (SPs) are synthesized in
      tissues in which malformations are later observed following treatment with the
      developmental toxicant, retinoic acid (RA), on day 11 of gestation (GD 11). These
      proteins were not synthesized in tissues which did not present with malformations
      near partuition. The purpose of the present investigation was to determine if
      this correlation between early SP synthesis and later malformation was present at
      other times during gestation. CD-1 strain mice were dosed orally with corn oil or
      100 mg/kg body weight RA on GD 10 or 13. Some of the mice in each group were
      given an intraperitoneal injection of 3H-leucine to label embryonic protein
      synthesis one hour after dosing with RA. These animals were sacrificed 1.5 hour
      later, and embryonic protein synthesis was determined by two-dimensional gel
      electrophoresis followed by autoradiography. Other animals in each group were
      sacrificed on day 17 of gestation, and fetuses were examined for the presence of
      malformations. Following treatment with RA on day 10 of gestation, malformations
      were observed in the forelimbs, the hindlimbs and the tail; heart defects were
      not observed. SPs of 20-25,000 and 90,000 relative molecular mass (Mr) were
      synthesized in the forelimb bud and tail; in addition, a second low molecular
      weight (20-25,000) and a 84,000 Mr SPs were synthesized in forelimb buds. No SPs
      were synthesized in the hindlimb bud or the heart. Following RA treatment on GD
      13, cleft palate was observed in 58% of fetuses; no other malformations were
      found. Proteins of 34,000, 84,000 and 90,000 Mr were synthesized in craniofacial
      tissue; SPs were not observed in forelimb bud, hindlimb bud, heart or tail
      tissues at this time. Therefore, it appears that there may be a correlation
      between tissue-specific SP synthesis early in organogenesis and the presence of a
      malformation later in gestation.

PMID- 7739352
TI  - Effect of chronic cocaine administration on amino acid uptake in rat placental
      membrane vesicles.
AB  - This study evaluated the effects of chronic exposure to cocaine during pregnancy
      on amino acid uptake in placental membrane vesicles. Pregnant rats received 62
      mg/kg of cocaine hydrochloride by intraperitoneal (IP) injection as a divided
      daily dose on gestation days 8-19 inclusive. Fetal body weights were
      significantly decreased by 19% in the cocaine group, while placental weights were
      unchanged. Placental apical membrane vesicles were prepared from control and
      cocaine-treated animals, and marker enzyme enrichments for alkaline phosphatase
      and [3H]-dihydroalprenolol binding did not differ between cocaine and control
      groups. Rates of uptake (10 sec) of selected radiolabeled amino acids were
      measured utilizing a rapid filtration technique. Na(+)-dependent apical membrane
      [3H]-glutamine transport (50 microM) was reduced by 95% (p < 0.05) in cocaine
      treated compared to control placentas. Uptake of 50 microM [3H]-methyl
      aminoisobutyric acid (MeAIB) into apical membranes was also decreased by 43% (p <
      0.05) in cocaine membranes. Na(+)-independent [3H]-arginine transport (10
      microM), however, did not differ between control or cocaine-treated groups. In
      summary, chronic cocaine administration selectively inhibited the transport of
      glutamine and MeAIB into apical membrane vesicles, but had minimal effect on
      arginine transport. We postulate that this diminution in uptake may contribute to
      the fetal growth retardation noted in our model.

PMID- 7739353
TI  - Hydroxyl radical formation in diabetic rats induced by streptozotocin.
AB  - Production of hydroxyl radicals was examined in the diabetic rats induced by
      streptozotocin to prove its involvement to the pathogenesis of diabetes. Hydroxyl
      radicals generated in plasma, heart muscle, liver and brain of the hyperglycemic
      rats were quantitatively assayed by trapping hydroxyl radicals with salicylic
      acid as 2,3- and 2,5-dihydroxybenzoic acid. The concentrations of 2,3- and 2,5
      dihydroxybenzoic acid were significantly increased in all the tissues of the
      diabetic rats. In the brain and heart muscle of the diabetic rats, the increase
      of 2,3-dihydroxybenzoic acid was more manifest than that of 2,5-dihydroxybenzoic
      acid, while in liver 2,5-dihydroxybenzoic acid increased markedly. All the values
      of 2,3-dihydroxybenzoic acid detected in the tissues of the diabetic rats were
      quite higher than those in control. Hydroxyl radical production and blood glucose
      concentration were depended almost linearly on the amount of streptozotocin
      injected to rats up to 60 mg/kg body weight. It was suggested that 2,3
      dihydroxybenzoic acid was produced from hydroxyl radicals themselves, while 2,5
      dihydroxybenzoic acid was produced by hydroxylation of salicylic acid not only
      with hydroxyl radicals, but also by enzymatic reaction of microsomal cytochrome
      P450. Hydroxyl radical formation may account for some pathological process
      especially in the heart muscle and brain.

PMID- 7739354
TI  - Response of glutamic acid decarboxylase to glucose but not arginine in islets.
AB  - This study examined responses of glutamic acid decarboxylase (GAD65) and gamma
      aminobutyric acid (GABA) to glucose in pancreatic islets. Islets isolated from
      Wistar rats were cultured for the three days under different concentrations of
      glucose (5.6, 11.1 or 16.7 mM) or arginine (2 x 10(-1)-2 x 10(-4) mM) for
      different periods of time. The expression of GAD65 increased 3.8- and 4.5-fold
      with the elevation of glucose concentrations as well as the prolongation of
      culture periods of time, while it did not increase with arginine. GABA content of
      islets did not change in a range of 5.6 to 16.7 mM glucose. These results suggest
      that normalization of hyperglycemia would reduce the expression of the
      autoantigen in islets, which might prevent islets from further destruction. To
      the contrary, the persistent hyperglycemia could interfere with insulin synthesis
      not by change of GABA in islets but by the destruction of islets through GAD65
      expression.

PMID- 7739355
TI  - Platelet serotonin transport is altered in streptozotocin-induced diabetic rats.
AB  - The present work was conducted to examine whether experimental diabetes
      (streptozotocin-induced) promotes changes in mean platelet volume, and platelet
      serotonin (5HT) uptake and content. These variables were measured in from four
      experimental groups: control, diabetic, diabetic+insulin, and non
      diabetic+insulin. Animals treated fifteen days before with streptozotocin had
      platelets with higher 5HT uptake affinity, 5HT content, and volume. The insulin
      therapy reestablished the control values of all of these three variables. Non
      diabetic animals treated one week with insulin did not show any variations. The
      effects of in vitro application of insulin, hyperglycaemic incubation medium, and
      streptozotocin on platelet amine uptake and release were also examined. Only
      those platelets incubated with streptozotocin showed an altered platelet 5HT
      uptake. No changes were observed for spontaneous 5HT release. The results are
      consistent with: a) an increase of platelet uptake capacity, as a consequence of
      an increase in platelet turnover, for explaining alterations of intraplatelet 5HT
      contents in experimental diabetes; b) a non-direct effect of insulin and glucose
      levels on platelet 5HT uptake -for explaining its dysfunctions in experimental
      diabetes-; c) the contribution of alterations in platelet 5HT transport for
      explaining the higher incidence of vascular complications in diabetic patients;
      d) the suitability of platelet as a model for investigating neuronal 5HT
      reuptake.

PMID- 7739356
TI  - Resting and thrombin-stimulated cytosolic calcium in platelets of patients with
      alcoholic withdrawal, bipolar manic disorder and chronic schizophrenia.
AB  - Cytosolic calcium concentration ([Ca2+]i) in platelets during resting state and
      when stimulated by thrombin were measured in 7 alcoholic dependent patients in
      the state of withdrawal (AW) who were receiving diazepam, 7 bipolar manic
      patients (BM) who were receiving haloperidol, 15 drug free chronic schizophrenic
      patients (CS) and 26 normal controls (NC). Resting [Ca2+]i in these groups were
      quite similar at (mean +/- SEM) 112 +/- 20 nM, 127 +/- 18 nM, 103 +/- 16 nM and
      106 +/- 8 nM respectively. Increase in platelet [Ca2+]i in response to 0.1 U/ml
      thrombin was expressed as delta[Ca2+]i and its percentage over resting [Ca2+]i as
      %[Ca2+]i. Both delta[Ca2+]i and %[Ca2+]i were significantly higher (p = 0.006 and
      0.0045 respectively, ANOVA, Waller-Duncan) in AW (433 +/- 71 nM, 417 +/- 58%)
      than the other groups: NC (223 +/- 25 nM, 225 +/- 23%), BM (309 +/- 38 nM, 260 +/
      31%), and CS (261 +/- 34 nM, 280 +/- 29%) respectively. In vitro incubation of
      platelets from NC with diazepam or haloperidol did not affect the resting [Ca2+]i
      and %[Ca2+]i. The enhanced [Ca2+]i response to thrombin in platelets of AW is
      unlikely to be due to diazepam. It may indicate an abnormality in platelets
      during the withdrawal phase. Treatment with haloperidol resulted in slightly
      higher [Ca2+]i in platelets of BM. Platelet [Ca2+]i in drug-free CS was not
      different from NC.

PMID- 7739357
TI  - Intracellular alkalinization by NH4Cl increases cytosolic Ca2+ level and tension
      in the rat aortic smooth muscle.
AB  - Intracellular pH (pHi) is elucidated to be an important regulator of various cell
      functions, but the role of pHi in smooth muscle contraction remains to be
      clarified. The purpose of the present study is to examine the effects of cell
      alkalinization by exposure to NH4Cl on cytosolic Ca2+ level ([Ca2+]i) and on
      muscle tone. We attempted simultaneous measurements of both [Ca2+]i and
      contractile force in rat isolated thoracic aorta from which the endothelium was
      removed. NH4Cl (10-80 mM) increased both [Ca2+]i and muscle tone in the presence
      of external Ca2+. These responses were reproducible. The removal of Ca2+ from the
      nutrient solution partially inhibited the rise in [Ca2+]i and the smooth muscle
      contraction induced by NH4Cl. In addition, the Ca2+ channel blocker verapamil
      also partially attenuated the responses to NH4Cl. The NH4Cl-induced responses
      were gradually reduced as NH4Cl was repeatedly added in a Ca(2+)-free solution.
      Norepinephrine (NE, 1 microM) induced a transient increase in [Ca2+]i and
      sustained contraction in the absence of external Ca2+, and the subsequent
      application of NE had little effect on [Ca2+]i. After internal Ca2+ stores were
      depleted by exposure to NE, the subsequent application of NH4Cl induced increases
      in [Ca2+]i and tension of the aorta in a Ca(2+)-free solution. These results
      suggest that NH4Cl mainly evokes Ca2+ release from the internal Ca2+ stores that
      are not linked with adrenergic alpha-receptor and causes Ca2+ influx through
      voltage-dependent Ca2+ channels in the vascular smooth muscle.

PMID- 7739358
TI  - Synovial thickening detected by MR imaging in osteoarthritis of the knee
      confirmed by biopsy as synovitis.
AB  - Previous studies have established the value of magnetic resonance imaging (MRI)
      in detecting articular changes characteristic of osteoarthritis (OA) of the knee.
      We have observed some MRI features in OA of the knee presumably indicating
      synovial thickening. To determine whether these MR features represent chronic
      synovial inflammation, we studied the knees of nine patients at the mild end of
      the spectrum of OA of relatively short duration (89%: < or = 4 yr), who were
      selected because MRI showed anatomical abnormalities compatible with synovial
      thickening. The painful knee was examined using conventional and weight-bearing
      radiographs, MRI, and arthroscopy. MR images suggestive of synovial thickening
      typically appeared in or near the intercondylar region of the knee, in the
      infrapatellar fat pad, or in the posterior joint margin. The site of an
      arthroscopic biopsy of the synovial membrane was guided by MRI to the area
      thought to represent synovial thickening for each patient knee. Pathological
      examination of these synovial membrane biopsies showed a mild chronic synovitis,
      and thus a correspondence with the synovial thickening detected by MRI. Our
      results suggest that MRI can be used to evaluate the extent of synovitis,
      observed as synovial thickening, in patients with early OA of the knee.

PMID- 7739359
TI  - Complementary use of T2-weighted and postcontrast T1- and T2*-weighted imaging to
      distinguish sites of reversible and irreversible brain damage in focal ischemic
      lesions in the rat brain.
AB  - The evolution of a photochemically induced cortical infarct was monitored using
      T2-, postcontrast (GdDOTA) T1-, and postcontrast (DyDTPA-BMA) T2*-weighted NMR
      imaging techniques. Data acquired with these different NMR imaging types were
      compared, both qualitatively and quantitatively. The T2*-weighted NMR images
      after spordiamide injection (DyDTPA-BMA) were perfusion-weighted images that
      allowed the differentiation between several infarct-related areas in terms of
      different degrees of perfusion deficiency. No quantitative information on
      cerebral blood flow (CBF) was obtained. A clear distinction was made between
      areas with a complete lack of CBF located in the core of the lesion and temporary
      CBF insufficiencies in the rim surrounding this core. Concomitant observations on
      T2-weighted and postcontrast T1-weighted images revealed the same temporary rim
      characterized by an increased water content, and an intact blood-brain barrier
      (BBB), as well as by reduced perfusion. This rim appeared within the first hours
      after infarct induction, reached a maximum 24 h later, and lasted between 3-5
      days, when its size gradually decreased until complete disappearance. These
      observations suggest the existence of an area at risk. Only on postcontrast T1
      weighted images, the core of the lesion remained visible during the whole
      experimental period (10 days) and reflected in all likelihood the irreversibly
      damaged ischemic central core. The combined application of different NMR imaging
      techniques when studying focal cerebral infarctions in the rat brain allowed us
      to distinguish, in terms of NMR characteristics, zones of reversible from
      irreversible brain damage and to estimate the severity of the damage. This might
      offer an appropriate experimental setup for the screening of cerebroprotective
      compounds.

PMID- 7739360
TI  - In vivo measurement of diffusion and pseudo-diffusion in skeletal muscle at rest
      and after exercise.
AB  - To investigate whether diffusion-related compartmentalization could be observed
      in skeletal muscle and whether this compartmentalization was affected by
      exercising, attenuation curves of signal against diffusion weighting were
      obtained in skeletal muscle of nine healthy volunteers at rest and after an
      exercise. Fifteen points were obtained for each diffusion curve with diffusion
      weightings ranging between approximately 0 and 560 x 10(6) s/m2. Data were fitted
      a biexponential model using three parameters to yield two apparent diffusion
      coefficients, a long one, ADCL, and a short one, ADCS, together with the
      fractional volume, fL, associated with the long one. At rest, values of
      parameters ADCL, ADCS, and fL were 46 x 10(-9) +/- 37 x 10(-9) m2/s, 1.74 x 10(
      9) +/- 0.11 x 10(-9) m2/s, and 3.6 +/- 1.3%, respectively. After exercise, these
      values were 89 x 10(-9) +/- 37 x 10(-9) m2/s (p < .001 vs. rest), 1.94 x 10(-9)
      +/- 0.13 x 10(-9) m2/s (p < .001), and 5.2 +/- 1.3% (p < .05), respectively.
      These variations demonstrate significant changes in attenuation curves between
      rest and postexercise in skeletal muscle and may support an interpretation of the
      long and the short components in terms of a microvascular and an extra
      microvascular compartments.

PMID- 7739361
TI  - Biodistribution and metabolism of targeted and nontargeted protein-chelate
      gadolinium complexes: evidence for gadolinium dissociation in vitro and in vivo.
AB  - The intracellular metabolism of receptor-targeted 153Gd-DTPA-glycoproteins was
      studied in vitro and in vivo. These agents bound to cell surface receptors,
      underwent receptor mediated endocytosis, and were rapidly degraded to a
      metabolite which co-migrated with a 153Gd-DTPA-lysine standard on thin layer
      chromatography. The rates of dissociation of 153Gd and 111In from a glycoprotein
      chelate conjugate were determined in vitro. Gadolinium readily dissociated, in a
      pH-sensitive manner, from glycoprotein-DTPA, and to a lesser degree glycoprotein
      MX-DTPA. The biodistribution of targeted and blood pool 153Gd/111In labeled
      proteins also suggested that gadolinium dissociates from protein-DTPA and protein
      MX-DTPA and their metabolites leading to an accumulation of gadolinium in bone.
      Metal-DTPA-glycoprotein agents targeted to cell surface receptors can still
      produce very high concentrations of radioactive or paramagnetic metals within the
      lysosome due to the high rate of accumulation afforded by receptor mediated
      endocytosis and the low release rate of metabolites such as metal-DTPA-lysine.
      However, the continued development of gadolinium based macromolecular agents will
      require improvements in bifunctional chelates.

PMID- 7739362
TI  - MRI evaluation of potential gastrointestinal contrast media.
AB  - Diluted ProHance [Gd(HP-DO3A), Squibb Diagnostics, Princeton, NJ], Sustacal
      (Meadjohnson, Evansville, IN), a nutritional drink, and a ProHance/Sustacal
      mixture have been investigated as potential oral contrast agents. At 2 T, T1
      weighted (SE 500/20) images demonstrated hyperintense (positive) signal
      enhancement of rat GI tracts within 10 min after the ingestion of 2.0 mM Gd(HP
      DO3A) or 2.0 mM ProHance/Sustacal. T2-weighted (SE 3000/80) images demonstrated
      hypointense (negative) signal intensity within 10 min after ingestion of 10 mM
      ProHance. Medical imaging applications of these oral contrast media are feasible.

PMID- 7739363
TI  - Kinetics of nitroxide spin label removal in biological systems: an in vitro and
      in vivo ESR study.
AB  - A systematic study on the disappearance of the electron spin resonance (ESR)
      signal of nitroxides based on six-or five-membered ring and bearing various
      charges was carried out in vitro and in vivo. The second-order kinetic rate
      constants of the reaction of spin probes with ascorbate were measured in vitro at
      various temperatures in phosphate buffered saline, and the relative activation
      energies were calculated. Clearance rates of the nitroxide radicals in rat brain
      homogenates and in blood indicate that the ascorbate contribution to nitroxide
      removal is about 50-70% in brain and 50-90% in blood. These rates can be easily
      calculated on the basis of the ascorbate concentration and of the second-order
      kinetic rate constants measured in phosphate buffered saline. ESR spectra
      acquired in vivo in rat head and tail, by an L-band resonator, indicated that the
      nitroxide decay rate is a first-order kinetic process in both domains and that
      the positively charged nitroxides are not retained in the brain, whereas the
      anionic and uncharged nitroxides are. Once nitroxides with piperidine ring enter
      the brain, their decay appears controlled mainly by ascorbate, while the
      ascorbate has a negligible influence on disappearance in brain of five-membered
      ring proxyl nitroxides.

PMID- 7739364
TI  - Magnetic resonance venography in liver bipartition procedures using preservation
      solution as contrast agent.
AB  - To evaluate whether the hepatic veins can be visualized with a rapid noninvasive
      technique, and if so, whether the obtained images could be helpful in the
      preparation of split liver grafts for transplantation, six cold stored human
      donor livers were investigated with magnetic resonance imaging (MRI). The hepatic
      vein branches and their confluence were clearly visualized. Anatomic variations
      of the middle hepatic vein with consequences for the choice of the transection
      plane could be demonstrated. Furthermore, unexpected vascular abnormalities were
      detected. From these preliminary results it is concluded that visualization of
      the hepatic veins can be helpful in determining the feasibility of the
      bipartition procedure and the choice of the transection plane. A potential wide
      application of this fast and noninvasive technique is possible.

PMID- 7739365
TI  - USPIO-enhanced MR imaging of glycerol-induced acute renal failure in the rabbit.
AB  - Enhanced-MR imaging in combination with ultrasmall superparamagnetic iron oxide
      (USPIO) was used in the glycerol-induced model of acute renal failure (ARF) in
      the rabbit to detect renal perfusion abnormalities. A control group (n = 5) and
      an ARF group (n = 5) were studied after intramuscular injection of glycerol (10
      ml/kg) with T2-weighted spin-echo sequence at 1.5 T and a 27 mumol/kg IV dose of
      iron. The signal intensity (SI) was quantified in the cortex, the outer medulla
      (OM), and the inner medulla (IM). In control rabbits, the maximum SI decrease
      after USPIO injection was in the OM (76% +/- 3.6), as this is the region of
      maximal vascular density, then in the IM (73.4% +/- 2.9). In the glycerol group,
      SI loss in the OM (61% +/- 12.6) and the IM (45.2% +/- 16.24) was significant
      less than in the control group (p < .05). Pathology results showed fibrinous
      thrombus in the efferent arterioles and congestive aspect of the vasa recta in
      the medulla. We argue that a reduced medullary concentration of USPIO in the
      renal failure group is indicative of medullary hypoperfusion.

PMID- 7739366
TI  - A matched filter echo summation technique for MRI.
AB  - A technique is presented to increase the signal-to-noise ratio (SNR) in two
      dimensional (2D), phase-encoded imaging at low SNR. The essence of this technique
      is to combine multiple echoes in the time domain. As analyzed in the paper, phase
      discrepancies exist among different echoes and may deteriorate the combined echo.
      In particular, extraneous phase shifts can be created if unshielded gradient
      coils are used. To overcome these phase discrepancies, a matched filter was
      derived from the k = 0 component of image. This matched filter has the same phase
      discrepancies among its echoes as the imaging signal and its magnitude decays
      with an average T2. In the echo summation with the matched filter, the phase of
      the matched filter was subtracted from the imaging signal and the magnitude of
      the matched filter was used as the weighting function. We have shown that this
      matched filter echo summation technique has better SNR than the case of 2D, phase
      encoded imaging in both simulation and experiment. The SNR improvement is up to
      60% in a phantom experiment. This technique is mostly useful in low SNR imaging
      that requires long imaging time, such as spectroscopic imaging and 19F imaging.

PMID- 7739367
TI  - In vivo relaxation time measurements on a murine tumor model--prolongation of T1
      after photodynamic therapy.
AB  - RIF tumors implanted on mice feet were investigated for changes in relaxation
      times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was
      performed using Photofrin II as the photosensitizer and laser light at 630 nm. A
      home-built proton solenoid coil in the balanced configuration was used to
      accommodate the tumors, and the relaxation times were measured before,
      immediately after, and up to several hours after therapy. Several control
      experiments were performed untreated tumors, tumors treated with Photofrin II
      alone, or tumors treated with laser light alone. Significant increases in T1s of
      water protons were observed after PDT treatment. In all experiments, 31P spectra
      were recorded before and after the therapy to study the tumor status and to
      confirm the onset of PDT. These studies show significant prolongation of T1s
      after the PDT treatment. The spin-spin relaxation measurements, on the other
      hand, did not show such prolongation in T2 values after PDT treatment.

PMID- 7739368
TI  - Effect of brine injection on water dynamics in postmortem muscle: study of T2 and
      diffusion coefficients by MR microscopy.
AB  - The dynamics of water in postmortem muscle were studied by magnetic resonance
      microscopy (MRM). Rabbit muscles were arterially injected with 3 and 5 M NaCl
      brine. T2 and diffusion mapping were performed during the onset of rigor mortis.
      A wide spread of T2 values and widely differing postmortem evolutions were
      observed for injected muscles, whereas T2 was spatially homogeneous for intact
      muscle. Also, highly variable spatial distribution of diffusion coefficients
      along (Dz) and across (Dx) the muscle fibers was observed and diffusion
      anisotropy Dz/Dx) was less marked in injected muscles. The results indicate
      heterogeneity of brine distribution far from the injection site soon after
      injection. The postmortem evolution of the parameters is discussed in terms of
      structural changes induced by brine injection. MRM provides insight into how
      water dynamics respond to different NaCl concentrations inside muscle.

PMID- 7739369
TI  - Estimation of water content and water mobility in the nucleus and cytoplasm of
      Xenopus laevis oocytes by NMR microscopy.
AB  - NMR microscopy is a noninvasive approach for studying cell structure and
      properties. Spatially resolved measurements of the relaxation times T1 and T2
      provided information on the water proton spin density and water mobility in
      different parts of Xenopus laevis oocytes. The spin-lattice relaxation time T1
      was determined using a saturation-recovery sequence and the common spin-echo
      sequence with increasing repetition times, while the transverse relaxation time
      T2 was measured by means of the spin-echo sequence with varying echo times. From
      the relaxation times, the mole fractions of possible reorientational correlation
      times tau c for different types of intracellular water were calculated according
      to a simple two-phase model. The values for T1, T2, and proton spin density
      (i.e., water content) are: nucleus >> animal cytoplasm > vegetal cytoplasm. Based
      on the estimation of tau c, nearly 90% of the nuclear water and 74.4% of the
      water of the animal pole was considered as free mobile water, whereas 55.5% of
      the water of the vegetal pole appeared as bound water.

PMID- 7739371
TI  - NMR imaging with shorted coaxial line probes.
AB  - At frequencies below 1 GHz, resonant sections of coaxial lines have long been
      used in CW-Electron Paramagnetic Resonance (EPR) with the sample placed at the
      position of maximum B1 at a short circuited end. Here, we show that because of
      the excellent separation of the B and E fields, the shield of the line can be
      removed in the region of the truncated end without greatly perturbing the RF
      properties of the line. The open region of the shield provides an aperture for
      local imaging in MRI. The B1 fields can be shaped by contouring the inner
      conductor and outer shield, and the image aperture is controlled by the shape of
      the shield cutout. The shield opening can range from a narrow longitudinal slit
      up to a full 360 degrees section that has only a few conducting strips of the
      shield remaining. Imaging with probes having shield diameters from 2 mm to 10 cm
      have been demonstrated. For imaging the useful depth is limited to approximately
      three to four times the probe's outer radius. Alternately, a relatively sharp
      cutoff at only a mm depth can be obtained by controlling the region of the shield
      removed, the RF power applied, and the probe diameter. The probes described here
      can be resonant or nonresonant. Because of the inherent broad bandwidth of the
      nonresonant truncated line probes, they have the potential for use in FT-EPR and
      FT-EPR imaging as well as other applications that require minimizing dead times.

PMID- 7739370
TI  - Application of fuzzy c-means segmentation technique for tissue differentiation in
      MR images of a hemorrhagic glioblastoma multiforme.
AB  - The application of a raw data-based, operator-independent MR segmentation
      technique to differentiate boundaries of tumor from edema or hemorrhage is
      demonstrated. A case of a glioblastoma multiforme with gross and histopathologic
      correlation is presented. The MR image data set was segmented into tissue classes
      based on three different MR weighted image parameters (T1-, proton density-, and
      T2-weighted) using unsupervised fuzzy c-means (FCM) clustering algorithm
      technique for pattern recognition. A radiological examination of the MR images
      and correlation with fuzzy clustering segmentations was performed. Results were
      confirmed by gross and histopathology which, to the best of our knowledge,
      reports the first application of this demanding approach. Based on the results of
      neuropathologic correlation, the application of FCM MR image segmentation to
      several MR images of a glioblastoma multiforme represents a viable technique for
      displaying diagnostically relevant tissue contrast information used in 3D volume
      reconstruction. With this technique, it is possible to generate segmentation
      images that display clinically important neuroanatomic and neuropathologic tissue
      contrast information from raw MR image data.

PMID- 7739372
TI  - A novel topical probe for MRI: the flat, truncated line probe.
AB  - The construction and imaging characteristics of flat, truncated line probes
      (FTLPs) are described here. These probes illustrate a novel design of local
      probes for magnetic resonance imaging, with four major differences from
      conventional loop surface probes: (1) The B1 fields are directed perpendicular to
      the usual loop probes' direction. (2) The RF fringe electric fields are
      inherently shielded, which allows reduced loading from electrically lossy
      samples. (3) The homogeneity across the plane of the probe can be adjusted
      locally. And (4) when not used with tuning and matching circuits, a probe's local
      impedance can be set to match the RF line impedance. The probes are, in essence,
      a single loop significantly flattened with the outside conductor (away from the
      imaged object) wider than the inside conductor (against the imaged object). The
      probes are shaped so as to provide a homogeneous signal across the plane area of
      the probe. The signal intensity drops off faster than a loop of the same size.
      With a minimally loading phantom, along the midline normal to the surface, the
      S/N at the surface region is approximately 20% greater than a commercial probe
      (Phillips R2) of the same area dimensions, while at 5 cm depth, the S/N is lower.
      However, when used for imaging a body--again along the midline normal to the
      probe--the S/N at 5 cm depth is equal, and rises to approximately twice that of
      the Philips R2 probe at the surface.

PMID- 7739373
TI  - Lactate quantification by means of press spectroscopy--influence of refocusing
      pulses and timing scheme.
AB  - The quantitative assessment of lactic acid in tissue is an important goal for in
      vivo volume-selective NMR spectroscopy to aid in the noninvasive diagnosis of
      oxygen deficiency of other metabolic disorders. PRESS localized 1H spectra
      provide comparatively high signal-to-noise ratio from small volume elements in a
      single acquisition mode. The quantification of lactate after multipulse
      excitation is not trivial due to the J-coupling characteristics which do not
      occur for the substances serving as references. The influence of the timing
      scheme and of the quality of the refocusing pulses was systematically evaluated
      for the lactate resonances by volume-selective measurements. Gaussian pulses,
      Hanning-filtered sinc pulses, and numerically optimized RE-BURP-pulses were
      applied for refocusing the magnetization in the PRESS sequence and the effects on
      the lactate AX3 spin system were compared. For these pulses, sequence parameters
      are presented providing high sensitivity to lactate signals. Timing schemes are
      shown which provide good quantification of lactate, even in cases with B1
      inhomogeneities or slight misadjustment of the transmitter amplitude. The
      combination of both echo times in the double-echo sequences clearly influences
      the signal characteristics of lactate at overall echo times near TE = 145 and 290
      ms, which may result in pure in-phase magnetization for this weakly coupled
      homonuclear system. Numerically optimized refocusing pulses (RE-BURP) provided up
      to 50% higher signal ratio of the methyl protons of lactate to uncoupled nuclei
      than the often used Hanning-filtered sinc pulses.

PMID- 7739374
TI  - An in vitro study at low field for MR guidance of a biopsy needle.
AB  - The aim of this study is to demonstrate in vitro that low field strength can be
      used for MR interventional procedures. At 0.1 T, we developed 3D, T1-, and T2
      weighted fast steady state sequences and measured the artifact created by an MR
      biopsy needle (22 gauge, 0.7 mm diameter) on a bicompartmental phantom. The
      artifact generated by the needle placed perpendicular to B0 did not exceed 3.6 mm
      for 3D steady state sequences and acquisition times reaching 1.5 s. Corresponding
      artifacts at higher field strength were 7.6 mm for 0.5 T and 8.6 mm for 1 T. Low
      field MRI proved to be potentially adaptable for the guidance of MR biopsy
      needles.

PMID- 7739375
TI  - MRI evaluation of diabetic muscle infarction.
AB  - Diabetic muscle infarction (DMI) is a painful and potentially serious
      complication in patients with poorly controlled diabetes mellitus. The incidence
      of DMI is likely much greater than reports in the literature suggest, perhaps
      secondary to the difficulty in making the diagnosis and excluding other more
      serious etiologies. This paper describes the role of MRI in the evaluation of a
      diabetic patient with a painful, swollen limb. Early application of MRI can more
      accurately classify the disease process and focus the differential diagnosis,
      thus avoiding the hazards of medical therapy associated with other etiologies
      such as deep venous thrombosis, cellulitis, or osteomyelitis. This paper
      describes the evaluation and diagnostic pitfalls encountered in two patients. MRI
      techniques and applications are presented with a discussion of clinical and
      radiological differential diagnoses.

PMID- 7739376
TI  - MRI of uterine leiomyosarcoma.
AB  - We report a case of a patient with uterine leiomyosarcoma. At MRI imaging, the
      patient was found to have a bilobed uterine mass with two components. While the
      caudal portion of the mass had the MRI appearance of a simple leiomyoma, the
      cephalad component showed atypical degeneration with an irregular contour.
      Malignant degeneration of a leiomyoma was confirmed by operative and histologic
      examination. We conclude that malignant degeneration should be considered on MR
      images of any degenerated leiomyoma showing an irregular contour.

PMID- 7739377
TI  - Hibernoma: MRI appearance of a rare tumor.
AB  - We report the features of a hibernoma on magnetic resonance (MR) imaging. The MR
      characteristics of this lesion were consistent with a complex lipid-containing
      mass. The mass did not suppress on short tau inversion recovery (STIR) imaging
      and was clearly not a simple lipoma. Hibernoma should be considered in the
      differential diagnosis of complex fatty masses.

PMID- 7739378
TI  - MR imaging of slipped stacked breast implants: a potential pitfall in the
      diagnosis of intracapsular rupture.
AB  - The integrity of silicone-gel breast implants can be evaluated by MR imaging. The
      findings of intra- and extracapsular rupture have been described. Increasingly
      sophisticated breast reconstruction techniques such as stacking of prostheses
      have lead to a wider range of implant appearances. We report a case where
      intracapsular rupture was simulated by slippage of two retropectoral stacked
      implants in relation to each other. The MR and CT findings are described.

PMID- 7739379
TI  - Sequence evolution of the porB gene of Neisseria gonorrhoeae and Neisseria
      meningitidis: evidence of positive Darwinian selection.
AB  - Protein 1 (PI) is a major porin of Neisseria gonorrhoeae and Neisseria
      meningitidis and is encoded by a single locus, porB. Alleles of the porB locus of
      N. gonorrhoeae are assigned to two homology groups, PI(A) and PI(B), on the basis
      of immunological and structural similarity. In a like manner, alleles of the porB
      locus of the closely related bacterium, N. meningitidis, are allocated into class
      2 and class 3 homology groups. An individual strain of N. gonorrhoeae or N.
      meningitidis expresses either one or other of these porin homology groups but
      never both, and the antigenic reactions of these highly diverse outer membrane
      proteins form part of the N. gonorrhoeae and N. meningitidis serotyping schemes.
      A comparison of the number of synonymous and nonsynonymous substitutions per site
      between the two most divergent alleles of each of these four groups of porB
      alleles shows that PI(A) alleles have accumulated significantly more
      nonsynonymous substitutions per site than synonymous substitutions. In contrast
      the distribution of synonymous and nonsynonymous substitutions between alleles of
      class 2 and class 3 porins are not significantly different from random. We
      localize the regions of the PI(A) alleles with an excess of amino acid changes to
      the surface-exposed loops of these outer membrane proteins and suggest that
      positive Darwinian selection for diversity, driven by the human immune system,
      can most easily explain the allelic polymorphism and the pattern of synonymous
      and nonsynonymous substitutions.

PMID- 7739380
TI  - Evolution at the tip and base of the X chromosome in an African population of
      Drosophila melanogaster.
AB  - Hitchhiking effects of advantageous mutations have been invoked to explain
      reduced polymorphism in regions of low crossing-over in Drosophila. Besides
      reducing DNA heterozygosity, hitchhiking effects should produce strong linkage
      disequilibrium and a frequency spectrum skewed toward an excess of rare
      polymorphisms (compared to the neutral expectation). We measured DNA polymorphism
      in a Zimbabwe population of D. melanogaster at three loci, yellow, achaete, and
      suppressor of forked, located in regions of reduced crossing-over. Similar to
      previously published surveys of these genomic regions in other populations, we
      observed low levels of nucleotide variability. However, the frequency spectrum
      was compatible with a neutral model, and there was abundant evidence for
      recombination in the history of the yellow and ac genes. Thus, some aspects of
      the data cannot be accounted for by a simple hitchhiking model. An alternative
      hypothesis, background selection, might be compatible with the observed patterns
      of linkage disequilibrium and the frequency spectrum. However, this model cannot
      account for the observed reduction in nucleotide heterozygosity. Thus, there is
      currently no satisfactory theoretical model for the data from the tip and base of
      the X chromosome in D. melanogaster.

PMID- 7739381
TI  - Molecular phylogeny and divergence times of drosophilid species.
AB  - The phylogenetic relationships and divergence times of 39 drosophilid species
      were studied by using the coding region of the Adh gene. Four genera-
      Scaptodrosophila, Zaprionus, Drosophila, and Scaptomyza (from Hawaii)--and three
      Drosophila subgenera--Drosophila, Engiscaptomyza, and Sophophora--were included.
      After conducting statistical analyses of the nucleotide sequences of the Adh,
      Adhr (Adh-related gene), and nuclear rRNA genes and a 905-bp segment of
      mitochondrial DNA, we used Scaptodrosophila as the outgroup. The phylogenetic
      tree obtained showed that the first major division of drosophilid species occurs
      between subgenus Sophophora (genus Drosophila) and the group including subgenera
      Drosophila and Engiscaptomyza plus the genera Zaprionus and Scaptomyza. Subgenus
      Sophophora is then divided into D. willistoni and the clade of D. obscura and D.
      melanogaster species groups. In the other major drosophilid group, Zaprionus
      first separates from the other species, and then D. immigrans leaves the
      remaining group of species. This remaining group then splits into the D. repleta
      group and the Hawaiian drosophilid cluster (Hawaiian Drosophila, Engiscaptomyza,
      and Scaptomyza). Engiscaptomyza and Scaptomyza are tightly clustered. Each of the
      D. repleta, D. obscura, and D. melanogaster groups is monophyletic. The splitting
      of subgenera Drosophila and Sophophora apparently occurred about 40 Mya, whereas
      the D. repleta group and the Hawaiian drosophilid cluster separated about 32 Mya.
      By contrast, the splitting of Engiscaptomyza and Scaptomyza occurred only about
      11 Mya, suggesting that Scaptomyza experienced a rapid morphological evolution.
      The D. obscura and D. melanogaster groups apparently diverged about 25 Mya. Many
      of the D. repleta group species studied here have two functional Adh genes (Adh-1
      and Adh-2), and these duplicated genes can be explained by two duplication
      events.

PMID- 7739382
TI  - The novel flightless-I gene brings together two gene families, actin-binding
      proteins related to gelsolin and leucine-rich-repeat proteins involved in Ras
      signal transduction.
AB  - The Drosophila melanogaster gene flightless-I, involved in gastrulation and
      muscle degeneration, has Caenorhabditis elegans and human homologues. In these
      highly conserved genes, two previously known gene families have been brought
      together, families encoding the actin-binding proteins related to gelsolin and
      the leucine-rich-repeat (LRR) group of proteins involved in protein-protein
      interactions. Both these gene families exhibit characteristics of molecular
      changes involving replication slippage and exon shuffling. Phylogenetic analyses
      of 19 amino acid sequences of 6 related protein types indicate that actin
      associated proteins related to gelsolin are monophyletic to a common ancestor and
      include flightless proteins. Conversely, comparison of 24 amino acid sequences of
      LRR proteins including the flightless proteins indicates that flightless proteins
      are members of a structurally related subgroup. Included in the flightless
      cluster are human and mouse rsp-1 proteins involved in suppressing v-Ras
      transformation of cells and the membrane-associated yeast (Saccharomyces
      cerevisae) adenylate cyclase whose analogous LRRs are required for interaction
      with Ras proteins. There is a strong possibility that ligands for this group
      could be related and that flightless may have a similar role in Ras signal
      transduction. It is hypothesized that an ancestral monomeric gelsolin precursor
      protein has undergone at least four independent gene reorganization events to
      account for the structural diversity of the extant family of gelsolin-related
      proteins and that gene duplication and exon shuffling events occurred prior to or
      at the beginning of multicellular life, resulting in the evolution of some
      members of the family soon after the appearance of actin-type proteins.

PMID- 7739383
TI  - Comparisons of nuclear-encoded small-subunit ribosomal RNAs reveal the
      evolutionary position of the Glaucocystophyta.
AB  - The Glaucocystophyta (e.g., Cyanophora paradoxa) form a morphologically distinct
      group of photosynthetic protists that is primarily distinguished by its cyanelles
      (= plastids). To elucidate their evolutionary relationships, we determined
      nuclear-encoded small-subunit ribosomal RNA (SSU rRNA) coding regions for four
      taxa classified in the Glaucocystophyta (C. paradoxa, Glaucocystis
      nostochinearum, Glaucosphaera vacuolata, Gloeochaete wittrockiana; sensu Kies and
      Kremer), and these sequences were positioned within the eukaryotic phylogeny.
      Maximum likelihood, maximum-parsimony, and neighbor-joining phylogenetic analyses
      show that the Glaucocystophyta is a relatively late-diverging monophyletic
      assemblage within the "crown" group radiation that forms a sister group to
      cryptophyte algae. Glaucosphaera vacuolata is a red alga and lacks some cyanelle
      (e.g., bounding peptidoglycan wall) and host cell (e.g., cruciate flagellar
      roots) characters typical of glaucocystophytes. Our data are consistent with a
      monophyletic origin of the cyanelle in the glaucocystophytes. The distribution of
      photosynthetic taxa within the glaucocystophytes/cryptophytes and other lineages
      such as the filose amoebae/chlorarachniophytes and heterokont protists provide
      clues to the origin of plastids with four bounding membranes. We speculate that
      multiple, likely independent, secondary endosymbioses gave rise to these
      plastids.

PMID- 7739384
TI  - High copy number of highly similar mariner-like transposons in planarian
      (Platyhelminthe): evidence for a trans-phyla horizontal transfer.
AB  - Several DNA sequences similar to the mariner element were isolated and
      characterized in the platyhelminthe Dugesia (Girardia) tigrina. They were 1,288
      bp long, flanked by two 32 bp-inverted repeats, and contained a single 339 amino
      acid open-reading frame (ORF) encoding the transposase. The number of copies of
      this element is approximately 8,000 per haploid genome, constituting a member of
      the middle-repetitive DNA of Dugesia tigrina. Sequence analysis of several
      elements showed a high percentage of conservation between the different copies.
      Most of them presented an intact ORF and the standard signals of actively
      expressed genes, which suggests that some of them are or have recently been
      functional transposons. The high degree of similarity shared with other mariner
      elements from some arthropods, together with the fact that this element is
      undetectable in other planarian species, strongly suggests a case of horizontal
      transfer between these two distant phyla.

PMID- 7739385
TI  - Conservation and dynamics of microsatellite loci over 300 million years of marine
      turtle evolution.
AB  - Microsatellite loci consisting of (CA)n repetitive arrays were obtained from
      three species of marine turtle, and primers were designed to test for
      polymorphism within species and the persistence of microsatellites across
      species. Homologous loci were found in each test of six marine species within two
      families (Cheloniidae and Dermochelyidae), as well as in a freshwater species
      (Emydidae, Trachemys scripta), which indicates a conservation of flanking
      sequences spanning approximately 300 million years of divergent evolution. The
      persistence of homologous microsatellites across marine turtles was confirmed by
      direct sequencing of loci across species and by the discovery of polymorphism in
      24 of 30 cross species tests. The conservation of flanking sequences could be due
      to a slow rate of base substitution in turtle nuclear DNA, as previously reported
      for mtDNA. In contrast, the presence of up to 25 alleles per locus per species
      indicates that the replication slippage events responsible for changes in allele
      length operate as in mammals. Comparisons of alleles among species revealed that
      alleles of the same length may not be homologous due to mutations within the
      flanking sequences. Levels of heterozygosity were consistently higher in species
      from which the primers were designed, which suggests problems with cross-species
      comparisons of variability. Within species, microsatellite variation between
      divergent populations was consistent with results from previous mtDNA studies
      indicating the usefulness of microsatellites for comparing male- versus female
      mediated gene flow.

PMID- 7739386
TI  - The expressed class II alpha-chain genes of the marsupial major
      histocompatibility complex belong to eutherian mammal gene families.
AB  - The major histocompatibility complex (Mhc) is a multigene family found in
      vertebrates. Mhc genes code for heterodimeric cell-surface molecules involved in
      presentation of peptides to T-lymphocytes. There are two classes of Mhc, and in
      eutherian mammals four main families of class II genes have been recognized; DR,
      DQ, DP, and DN/DO. Each class II family contains genes that code for one or more
      alpha and beta chains. Do the class II genes of marsupial mammals belong to any
      of these eutherian mammal class II families? The results to date are conflicting.
      The expressed class II beta-chain genes could not be satisfactorily assigned to
      any eutherian class II gene family and were designated as new gene families,
      while, conversely, a partial sequence of an expressed alpha-chain gene was
      clearly very similar to the DNA gene of eutherian mammals. The aim of this study
      was to conduct a more thorough analysis of the alpha-chain genes in a marsupial
      by obtaining full-length sequences of all the expressed alpha-chain genes in the
      red-necked wallaby, Macropus rufogriseus. Two class II alpha-chain genes were
      isolated from a spleen-derived cDNA library, and both have the potential to code
      for fully functional MHC molecules. Phylogenetic analysis indicated they belonged
      to previously identified eutherian class II families and are designated as Maru
      DRA and Maru-DNA. Northern blot data indicated processed transcript sizes of
      approximately 1.6 kb for Maru-DRA and approximately 2.5 kb for Maru-DNA and that
      the latter was expressed at a lower level than the former. The phylogeny shows
      that the DR, DQ, DP, and DN/DO gene families diverged prior to the divergence of
      the marsupial and eutherian mammal lineages.

PMID- 7739387
TI  - On the use of nucleic acid sequences to infer early branchings in the tree of
      life.
AB  - Simplifying assumptions made in various tree reconstruction methods--notably rate
      constancy among nucleotide sites, homogeneity, and stationarity of the
      substitutional processes--are clearly violated when nucleotide sequences are used
      to infer distant relationships. Use of tree reconstruction methods based on such
      oversimplified assumptions can lead to misleading results, as pointed out by
      previous authors. In this paper, we made use of a (discretized) gamma
      distribution to account for variable rates of substitution among sites and built
      models that allowed for unequal base frequencies in different sequences. The
      models were nonhomogeneous Markov-process models, assuming different patterns of
      substitution in different parts of the tree. Data of the small-subunit rRNAs from
      four species were analyzed, where base frequencies were quite different among
      sequences and rates of substitution were highly variable at sites. Parameters in
      the models were estimated by maximum likelihood, and models were compared by the
      likelihood-ratio test. The nonhomogeneous models provided significantly better
      fit to the data than homogeneous models despite their involvement of many
      parameters. They also appeared to produce reasonable estimation of the
      phylogenetic tree; in particular, they seemed able to identify the root of the
      tree.

PMID- 7739388
TI  - Patterns of genetic variability at individual minisatellite loci in minke whale
      Balaenoptera acutorostrata populations from three different oceans.
AB  - The genetic variability at six cloned minisatellite loci was analyzed in minke
      whale populations from the North Atlantic, North Pacific, and Antarctic Oceans.
      Three loci displayed only a few different alleles in each of the three
      populations, with heterozygosity ranging from 0.00 to 0.47, and three loci
      revealed many different alleles in at least two fo the three populations, with
      heterozygosity ranging up to 0.98. Using small sample sizes, samples from two
      adjacent Antarctic Management Areas were not found to differ significantly in
      allele frequencies at any of the six loci. The use of principal coordinate
      analysis to detect multilocus disequilibria was explored. No significant evidence
      was found of intrapopulation heterogeneity within the pooled Antarctic sample.
      Pronounced interoceanic differences were observed at every locus, confirming the
      existence of genetic isolation found earlier using more conventional marker
      systems. The populations from the three oceans appear to have diverged to such a
      degree that the hypervariable loci have had time to evolve independently and
      arrive at different evolutionary stages in different populations. The frequency
      of undetected "null" alleles is remarkably high in minke whale populations
      compared to human populations and is probably a result of the cloning protocol
      used. Minisatellite loci are shown to provide a powerful population genetic tool,
      supplying levels of resolution appropriate to different degrees of evolutionary
      divergence.

PMID- 7739389
TI  - Hitchhiking and associative overdominance at a microsatellite locus.
AB  - The possible effects of a selected locus on a closely linked microsatellite locus
      are discussed and analyzed in terms of coalescent theory and models of the
      mutation process. Background selection caused by recurrent deleterious mutations
      will reduce the variance of allele size at a microsatellite locus. The occasional
      substitution of advantageous alleles (genetic hitchhiking) will also reduce the
      variance, but a high mutation rate at a microsatellite locus can restore the
      variance relatively rapidly. Overdominance at the selected locus will increase
      the variance at the microsatellite locus and create partitioning of the variation
      in allele size among gametes carrying one or the other of the overdominant
      alleles. These results suggest that neutral microsatellite loci can provide
      indicators of selective processes at closely linked loci.

PMID- 7739390
TI  - The concerted evolution of 5S ribosomal genes linked to the repeat units of other
      multigene families.
AB  - We review all instances in which the nuclear 5S rRNA genes of fungi, protist,
      nematode, and arthropod species have been reported to be linked to the tandemly
      repeated units of the rDNA, trans-spliced leader, and histone multigene families.
      The evolution of these gene arrangements is analyzed by mapping them to
      independently derived phylogenies. These analyses show that 5S rRNA genes have
      repeatedly become linked to diverse tandemly repeated gene families and that such
      linkages have also been subsequently inverted or lost in some species. These
      variable gene linkages are probably the result of stochastic gains and losses of
      variant repeat units, where functional 5S rRNA had transposed, by the mechanisms
      which are responsible for the concerted evolution of tandemly repeated multigene
      families. We discuss the possible mechanisms of 5S rRNA gene transposition and
      suggest that the characteristics of their promoter elements, transcription, and
      termination signals may allow functional copies of these genes to be fortuitously
      transposed through an RNA intermediate. We also review the evidence which shows
      that the linked 5S rRNA gene copies are transcribed. We conclude that the
      observed patterns of 5S rRNA gene linkages to the repeat units of other tandemly
      repeated multigene families have likely arisen due to fortuitous recombination
      events and are unlikely to represent the remnants of an eubacterial-like
      arrangement of rDNA operons or to have been established due to selective
      pressures.

PMID- 7739391
TI  - Testing the covarion hypothesis of molecular evolution.
AB  - The covarion hypothesis of molecular evolution states that the fixation of
      mutations may alter the probability that any given position will fix the next
      change. Tests of this hypothesis using the divergence of real sequences are
      compromised because models of rate variation among sites (e.g., the gamma version
      of the one-parameter equation) predict sequence divergence values similar to
      those for the covarion process. This study therefore focuses on the extent to
      which the varied and unvaried codons of two well-diverged taxa are the same,
      because fewer are expected by the covarion hypothesis than by the gamma model.
      The data for these tests are the protein sequences of Cu, Zn superoxide dismutase
      (SOD) for mammals and plants. Simulation analyses show that the covarion
      hypothesis makes better predictions about the frequencies of varied and unhit
      positions in common between these two taxa than does the gamma version of the one
      parameter model. Furthermore, the analysis of SOD tertiary structure demonstrates
      that mammal and plant variabilities are distributed differently on the protein.
      These results support the conclusions that the variable and invariable codons of
      mammal and plant SODs are different and that the covarion model explains the
      evolution of this protein better than the gamma version of the one-parameter
      process. Unlike other models, the covarion hypothesis accounts for rate
      fluctuations among positions over time, which is an important parameter of
      molecular evolution.

PMID- 7739392
TI  - Evolutionary potential of the ebgA gene.

PMID- 7739393
TI  - Novel phylogeny of whales revisited but not revised.

PMID- 7739394
TI  - A mitochondrial DNA discontinuity in the mussel Mytilus galloprovincialis Lmk:
      pleistocene vicariance biogeography and secondary intergradation.

PMID- 7739395
TI  - Procedures for the detection of chemically induced aneuploidy: recommendations of
      a UK Environmental Mutagen Society working group.
AB  - The development of assays to detect numerical chromosome aberrations has not kept
      pace with that for assays used to detect other genotoxicity endpoints such as
      gene mutations and structural chromosome aberrations, even though the importance
      of aneuploidy in relation to heritable defects in germ cells and to
      carcinogenesis in somatic cells is acknowledged. Regulatory bodies at present
      have no formal requirements concerning aneuploidy detection and decisions are
      made on a case-by-case basis. The aim of this review is to indicate which assays
      are available for the detection of chemically induced aneuploidy and what aspects
      should be taken into account when testing for chemically induced aneuploidy using
      in vitro, in vivo somatic and in vivo germ cell assays without dictating exact
      protocols. Our recommendations concentrate on systems that, to date, have been
      most extensively used and we indicate where future developments may lie. It is
      important that the currently available and future tests for chemically induced
      aneuploidy should be adequately validated before being implemented into screening
      strategies or regulatory guidelines. This requirement has not yet been met and is
      confounded by the lack of a well defined reference database of animal and human
      chemical aneugens.

PMID- 7739396
TI  - Induction of micronuclei in metabolically competent rat hepatoma cell lines by
      the promutagens 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene and
      cyclophosphamide.
AB  - The capability of two rat hepatoma cell lines, H4IIEC3/G- and 2sFou, to detect
      genotoxicity of xenobiotics, was evaluated in a micronucleus assay. In this
      system, the cells act as the activation source as well as the target cells for
      the DNA damage. The study was performed using 7,12-dimethylbenz[a]anthracene,
      benzo[a]pyrene and cyclophosphamide, as pro-mutagens and mitomycin C as a direct
      acting mutagen. In both cell lines a significant micronucleus induction was
      observed after exposure to each test compound, starting from 25 nM for 7,12
      dimethylbenz[a]anthracene, 8 microM for benzo[a]pyrene, 0.5 mM for
      cyclophosphamide and 0.4 microM for mitomycin C. A period of 24 h treatment and
      48 h growth was sufficient for induction and expression of micronuclei. The two
      hepatoma lines behave in a similar way with regard to the pro-mutagen activation.
      The results obtained in this study with these differentiated hepatoma lines
      demonstrate that they are metabolically competent to activate the promutagens
      7,12-dimethylbenz[a]anthracene, benzo[a]pyrene and cyclophosphamide into their
      biologically active metabolites as measured by micronucleus induction in our
      experiments. However, the variable dose responses to 7,12
      dimethylbenz[a]anthracene and benzo[a]pyrene in some of the repeated experiments,
      suggest unstable activity of enzymes involved in polycyclic aromatic hydrocarbons
      metabolism in these cell lines.

PMID- 7739397
TI  - Clastogenic and aneugenic effects of three benzimidazole derivatives in the in
      vitro micronucleus test using human lymphocytes.
AB  - Three benzimidazole compounds thiabendazole (TBZ), carbendazim (MBC) and
      mebendazole (MEB) were analysed with the in vitro cytochalasin-B micronucleus
      test on human lymphocytes. TBZ was tested in isolated lymphocyte cultures and MBC
      and MEB were tested in both isolated lymphocyte and whole blood cultures. TBZ was
      tested up to 300 microM with and without S9-mix. Although signs of toxicity,
      without S9, were observed by a decrease in the division index at 300 microM, an
      increase in the frequency of micronucleated binucleates was not found with or
      without S9. MBC and MEB induced a statistically significant concentration
      dependent increase in the micronucleus frequency. The effective concentration
      range for MEB (0.3-1.5 microM) was ten times lower than for MBC (5-25 microM). By
      means of fluorescence in situ hybridization with a 30 nucleotide oligomer of the
      alpha centromeric regions, common for all chromosomes, on the induced micronuclei
      MBC and MEB were found to induce a significant increase of centromere positive
      micronuclei in a dose-dependent manner. MBC and MEB are poorly soluble in water
      and therefore have a low bioavailability in vivo. However, increased micronucleus
      frequencies were found in this in vitro micronucleus study at doses comparable to
      in vivo plasma levels in mice and should, therefore, not be neglected in the risk
      evaluation of those compounds.

PMID- 7739398
TI  - Combination effects of clastogens in the mouse peripheral blood micronucleus
      assay.
AB  - In order to study how two chemicals interact to induce micronuclei, simple
      ethylating agents [ethyl methanesulfonate (EMS), ethyl ethanesulfonate (EES) and
      N-ethyl-N-nitrosourea (ENU)], spindle poisons [vincristine sulfate (VINC) and
      colchicine (COL)] and an oxidizing agent [potassium bromate (KBrO3)] were used as
      model chemicals for combination treatments. The frequency of micronucleated
      reticulocytes (MNRETs) was evaluated in mice treated with two of these chemicals
      at a time. The combinations of ethylating agents (EMS and EES; EMS and ENU) and
      of spindle poisons (VINC and COL) induced more micronuclei than those expected on
      an additive basis. The apparent synergism was due to a 'combined dose' which
      could be calculated by the dosimetric conversion of one chemical to the other,
      when damage induced by each chemical was 'equivalent' in the induction of MNRETs.
      In contrast, no apparent synergism in induction of micronuclei was observed when
      two chemicals with different modes of clastogenic action (EMS and KBrO3 or EMS
      and VINC) were combined.

PMID- 7739399
TI  - Neocarzinostatin induces chromosomal aberrations and sister chromatid exchanges
      in Chinese hamster ovary cells.
AB  - Chinese hamster ovary (CHO) cells were treated with neocarzinostatin (NCS) and
      analyzed for chromosomal aberrations and sister chromatid exchanges (SCE). After
      treatment the cells were recovered for 9, 20, 26 or 30 h. NCS induces chromosomal
      aberrations and SCE. SCE were much more frequent in cells with chromosome type
      aberrations at 20 h recovery time than in those with chromatid type aberrations
      at 9 h recovery time. In second post-treatment cells at 26 or 30 h recovery time
      NCS induced chromosomal aberrations but only few SCE.

PMID- 7739400
TI  - Urinary and serum mutagenicity studies with rats bearing experimental tumours.
AB  - Urine and serum samples of rats bearing three different experimental tumours
      (hepatocellular carcinoma, myelomonocytic leukemia and mesoblastic nephroma) were
      investigated for mutagenicity with the Ames Salmonella test. Enhancement of
      mutagenic activity in TA98 and TA100 was observed only in the case of urine
      samples obtained from animals bearing nephromas. Mutagenicity increased with
      increasing time after implantation of tumours. There was no coincidence between
      urinary and serum mutagenicity under the experimental conditions employed.
      Further studies are needed to determine the origins, and chemical and genotoxic
      characteristics of urinary mutagens. In addition, the question as to whether any
      mutagenic substances can be detected in fractions of plasma/serum should also be
      experimentally addressed.

PMID- 7739401
TI  - Bacterial mutagenicity of cigarette smoke and its interaction with ethanol.
AB  - The mutagenicities of mainstream cigarette smoke (CS), a cigarette smoke
      condensate (CSC) and smokers' urines were investigated by using batteries of
      Salmonella typhimurium and Escherichia coli strains. The S9-mediated mutagenicity
      of CSC was remarkably enhanced when using nitroreductase- and especially O
      acetyltransferase-overproducing derivatives of the classical strains TA98 and
      TA100, with the following rank of sensitivity: YG1024 > YG1029 > YG1021 > TA98NR
      > YG1026 > TA98 > TA100 > TA100-DNP6 > TA100NR > TA98-1,8-DNP6. With YG1024, a
      doubling of spontaneous revertants was observed with as little as 1/110 of the
      smoke condensate recovered from one cigarette under our experimental conditions.
      Similarly, the S9-mediated mutagenicity of mainstream CS was considerably
      increased in YG1024 and YG1029, the O-acetyltransferase-overproducing derivatives
      of TA98 and TA100, respectively. In the absence of S9 mix, the concentrates of 23
      urine specimens from five smokers failed to revert S. typhimurium TA98 and
      YG1024, and were equitoxic in E. coli WP2 and its repair-deficient counterpart
      CM871 (uvrA-, recA-, lexA-). In the presence of S9 mix, all specimens were
      mutagenic, with an average YG1024:TA98 ratio of 6.6:1. These patterns suggest
      that the bacterial mutagenicity of smoke-associated complex mixtures is mainly
      due to aromatic amines. The mutagenicities of other typical constituents of CS,
      i.e. the polycyclic aromatic hydrocarbon benzo[a]pyrene (BP) and the tobacco
      specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), were
      not appreciably enhanced in the O-acetyltransferase-overproducing strain YG1029,
      compared to its parental strain TA100. Moreover, BP and NNK induced less than
      additive mutagenic responses when combined at high doses.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7739403
TI  - Telemedicine in Michigan.

PMID- 7739404
TI  - Give your practice a spring tune-up.
AB  - Like your car, your medical practice may need some spring adjustments. Although
      some of the newer automobiles can travel 100,000 miles between "tune-ups," the
      business side of your medical practice requires more frequent attention. Many
      times physicians believe that their practice may run on autopilot, until they
      begin to see acute signs of problems. Such complacency can often lead to
      surprises that will ultimately impact your patients, your staff and your bottom
      line.

PMID- 7739402
TI  - Extensive loss of heterozygosity accounts for differential mutation rate on
      chromosome 17q in human lymphoblasts.
AB  - In order to investigate the influence of loss of heterozygosity (LOH) events on
      mutation rate, we studied two closely related human lymphoblastoid cell lines,
      AHH-1 (h2E1.v2) and MCL-5, which are heterozygous at the tk locus (chromosome
      17q23-25). Although they have similar mutant fractions at the hprt locus, the
      mutant fraction and rate at tk is four to five times higher in AHH-1. Analysis of
      58 spontaneous TK- mutants from AHH-1 and MCL-5 showed that the occurrence of LOH
      events was more frequent (23/24) in AHH-1 than MCL-5 (16/34). A set of five
      microsatellite polymorphism loci was used to map the extent of LOH along
      chromosome 17q. In AHH-1 cells, 15/23 of the LOH events encompassed at least 35%
      of the sex-averaged genetic length of chromosome 17q (98 cM). Additionally, the
      next most extensive category of LOH accounted for 5/23 TK- mutants, and
      encompassed at least 17 cM. In contrast, LOH events observed in MCL-5 are very
      restricted in extent; only one LOH tract extended as far as 4 cM from tk. The
      higher mutation rate at tk in AHH-1 can, therefore, be entirely attributed to the
      recovery of chromosomal scale LOH in viable, normal growth TK- mutants.
      Furthermore, these data demonstrate that the regional potential for LOH is likely
      to be an important determinant of mutation rate for loci within that chromosomal
      segment.

PMID- 7739405
TI  - Practice parameters: a state's rights issue?

PMID- 7739406
TI  - Stark II bans 11 "designated health services".
AB  - Effective January 1, 1995, Stark II prohibits physicians or their immediate
      family members who have a "financial relationship" with an entity from referring
      their patients to the entity for "designated health services" covered by either
      Medicare or Medicaid. Stark I prohibited self-referral only for Medicare-covered
      clinical laboratory services. Stark II expands the ban to a list of 10 additional
      "designated health services" and applies when these services are covered by
      Medicaid, as well as Medicare.

PMID- 7739407
TI  - Kronenberg vs. Henry Ford Health System, et al. addresses constitutionality of
      malpractice reform legislation.
AB  - In November 1994, a Wayne County Circuit Court judge rendered an opinion
      upholding the constitutionality of the 182-day pre-suit notice and waiting
      requirements under the Malpractice Reform Legislation which became effective
      April 1, 1994. The Court's opinion is well written and will lend support to other
      constitutional attacks taking place in other circuit courts. It is expected that
      the Kronenberg case will be appealed. MSMS legal counsel will monitor this and
      other cases contesting the constitutionality of the Malpractice Reform
      Legislation and keep MSMS members apprised.

PMID- 7739408
TI  - CD4 similarity to proteins of infectious agents in AIDS and their role in
      autoimmunity.
AB  - Lymphocytotoxic autoimmunity (LA) is ubiquitous in AIDS. Its causes are unknown.
      We report that significant amino acid sequence similarities exist between the
      proteins of infectious organisms associated with AIDS and the CD4 protein of T
      helper lymphocytes. These included: HIV, cytomegalovirus (CMV), Epstein-Barr
      virus (EBV), herpes simplex viruses (HSV), Varicella Zoster virus (VZV),
      Escherichia coli, Mycobacteria, Mycoplasmas, Plasmodium, and Staphylococcus. It
      has been reported previously that HIV proteins have significant similarities with
      human class II MHC (HLA class II) proteins. Since CD4 and HLA class II proteins
      are chemically complementary, pairs of homologous antigens will also be
      complementary. It follows that concurrent infections with CD4 and HLA class II
      homologous antigens will result in idiotype-antiidiotype antibody pairs that
      cannot distinguish 'self' from 'nonself', that acts as lymphocytotoxins, and form
      circulating immune complexes. Thus, combined HIV-CMV, HIV-EBV, HIV-HBV, HIV
      mycoplasma, or other appropriate infectious pairs may suffice to trigger LA in
      AIDS.

PMID- 7739409
TI  - A hypothesis on the aetiology of Alzheimer's disease: description of a model
      involving a misfolded chaperone.
AB  - A model is proposed to explain the aetiology of Alzheimer's disease. It is based
      on theoretical considerations of protein folding involving molecular chaperones.
      It explains how a misfolded chaperone gives rise to new misfolded chaperones.
      Such a protein replicates misfolding and invades the cell. The invasion appears
      sporadically, its probability increasing with time; a mutation or an increased
      synthesis of this chaperone shorten the delay before invasion. These
      characteristics are those of Alzheimer's disease. The model implies that one of
      the proteins involved in pathogenesis is a molecular chaperone. The possible
      function as molecular chaperone of the protein expressed by genes involved in the
      disease is discussed. It is shown that the beta-amyloid precursor protein (APP)
      as well as apolipoprotein E exhibit some properties of a genuine molecular
      chaperone. I propose that Alzheimer's disease results from the invasion of the
      nervous system by a misfolded molecular chaperone.

PMID- 7739410
TI  - Meiotic dynamics in mammalian seminal cells.
AB  - The paper discusses certain dynamic processes leading to meiotic (haploid)
      partition of chromatids via the chiasmatic mode in mammalian spermatic cells. The
      achiasmatic case is also reviewed briefly and only in the context of homologs
      with centromeric braids arrayed in the Para configuration.

PMID- 7739411
TI  - Molecular mimicry in the pathogenesis of AIDS: the HIV/MHC/mycoplasma triangle.
AB  - The immune defects characterizing infection with the human immunodeficiency virus
      (HIV) and culminating in the acquired immune deficiency syndrome (AIDS) are the
      result of a multifactorial disease process, components of which are the
      occurrence of autoimmune phenomena and opportunistic infection. In this
      discussion, the observation that both the HIV-1 gp 120 envelope and Mycoplasma
      genitalium adhesin proteins share an area of significant similarity with the CD4
      binding site of the class II major histocompatibility complex (MHC) proteins is
      placed in this perspective and mechanisms by which interaction within this triad
      could contribute to the T-cell dysfunction, T-cell depletion, Th1-cell-->Th2-cell
      shift, B-cell proliferation, hyperglobulinemia and antigen-presenting cell
      dysfunction observed during the development of AIDS are proposed.

PMID- 7739412
TI  - From superstitious behavior to delusional thinking: the role of the hippocampus
      in misattributions of causality.
AB  - Nearly half a century ago B. F. Skinner proposed the hypothesis that human
      superstitiousness would be equivalent to the 'superstitious' behavior displayed
      by animals in operant situations involving response-independent reinforcement.
      Surprisingly, no attempt has ever been made to test this equivalence hypothesis
      experimentally. In the light of recent evidence for a common neurological basis
      of both superstitious beliefs held by normal subjects and delusional ideas of
      psychotic patients, Skinner's hypothesis has become topical again. We present an
      extension of the hypothesis which assumes dysfunction of the medial temporal
      lobe, in particular of the hippocampus, to be responsible for conditioned
      superstitions in animals, for common everyday superstitions, and for
      schizophrenic delusions. This hypothesis is based on (1) the observation of an
      enhanced 'superstitious' reactivity in hippocampectomized animals, (2) findings
      of an increased occurrence of popular superstitions in patients with a temporal
      limbic epileptic focus, and (3) morphological and pharmacological evidence for
      schizophrenic delusions to be causally related to hippocampal damage.

PMID- 7739413
TI  - A model for systemic lupus erythematosus based on chromatin disruption by
      polyamines.
AB  - Here it is hypothesized that some autoimmune disorders, such as systemic lupus
      erythematosus, result in part from overexpression of polyamines which leads to
      disruption of chromatin structure. Disruption of inactive chromatin, such as the
      inactive X chromosome, exposes sites of unrepaired DNA damage. Repair is then
      hampered by the polyamines. Disruption also facilitates transcription at
      previously sequestered sites. Especially interesting are RNA polymerase III sites
      in highly repeated sequences such as the Alu sequence. Transcription and
      translation from these sites could create RNA and polypeptides not normally
      expressed. These could be antigenic either individually or in association with
      other cellular components. Interactions of polyamines in the nucleus and with the
      membrane could also lead to polyamine facilitated apoptosis.

PMID- 7739415
TI  - Can linoleic acid and gamma-linolenic acid be important in cancer treatment?
AB  - This hypothesis proposes that the essential fatty acids (EFAs), linoleic acid
      (LA) and gamma-linolenic acid (GLA), play important roles in cancer treatment.
      Oxidation of LA by lipoxidase especially increases tumour cell death, whilst GLA
      inhibits urokinase-type plasminogen activator (uPA) activity. Increased uPA
      activity is: firstly, responsible for cancer invasion and metastasis and
      secondly, responsible for proteolysis of lipoxidase which favours a decrease in
      cancer cell death. Addition of LA and GLA to available therapeutic regimens may
      be worth considering in cancer treatment.

PMID- 7739414
TI  - A selenium transport protein model of a sub-type of schizophrenia.
AB  - The model presented here suggests that a defect in a selenium transport protein
      may be a necessary but not sufficient precondition for a sub-type of
      schizophrenia--a type of schizophrenia that has been characterized by negative
      symptoms, brain damage, and a lack of primarily paranoid ideation. A defective
      selenium transport protein and consequent low levels of selenium might adversely
      affect multiple enzyme systems. Selenium-enzyme interreactions are discussed and
      the effect of selenium on arachidonic acid and its metabolites, especially 12
      HPETE, are examined in light of the presented model. If the proffered model is
      essentially correct, selenoprotein P, a hypothesized selenium transport protein,
      is a likely candidate for a protein involved in the etiology of a form of
      schizophrenia.

PMID- 7739416
TI  - Possible role and mechanism of inactivation of decidual NK cells in pregnancy.
AB  - Decidual NK cells are present in murine decidua in early pregnancy, but they
      decline by midpregnancy. The participation of these cells in rapid rejection of
      abnormal fetuses and possible cytolitic activity of these cells to trophoblasts
      seems unlikely. But, their production of cytokines (like CSF-1, which promote
      differentiation and growth of trophoblasts cells) may be the primary role of
      decidual NK cells in time of establishment of fetal-maternal connection. Later,
      inactivation of decidual NK cells by prostaglandins prevents damage of embryos.

PMID- 7739417
TI  - Schizophrenia is a diabetic brain state: an elucidation of impaired
      neurometabolism.
AB  - In this paper a detailed argument will be advanced in support of the notion that
      schizophrenia is fundamentally a diabetic brain state, henceforth referred to as
      'cerebral diabetes'. Many extraneous features of cerebral diabetes have been
      observed, including positron emission tomography (PET) scans which reflect
      abnormal distribution patterns and diminished supplies of glucose in the brain.
      Equally, empirical research has demonstrated that plasma levels of essential
      fatty acids and prostaglandins are abnormally low, and low levels of
      glycoproteins in the urine of cerebral diabetics have also been observed. In
      addition, cerebral diabetics manifest a wide range of disturbing physical
      symptoms, such as, impaired sexual function, temperature control, low blood
      pressure, disrupted sleep patterns, excessive thirst, poor memory, insensitivity
      to pain, and chronic unhappiness, all of which can be attributed to disrupted
      neuroendocrine function. Thus, in order to persuasively assert the redefinition
      of schizophrenia as 'cerebral diabetes', we shall first explicate glucose
      regulation and transport in the brain and then outline how this interacts with
      essential fatty acids and prostaglandins, neurotransmission, and the
      neuroendocrine system. In so doing, we shall provide a metabolic explanation for
      all the prominent symptoms currently known to be associated with cerebral
      diabetes and indicate some future therapeutic interventions.

PMID- 7739418
TI  - The modern Coroner--is reform overdue?

PMID- 7739419
TI  - "Super-specialists" and the Bolam test.

PMID- 7739420
TI  - Does the doctor know best--what is the scope for non-consensual treatment?

PMID- 7739421
TI  - Metformin for non-insulin-dependent diabetes mellitus.

PMID- 7739422
TI  - Treatment of nerve gas poisoning.

PMID- 7739423
TI  - [Morphologic characteristics of the superior temporal gyrus vascular network].
AB  - The investigation of the morphological features of vascular network of superior
      temporal gyrus was carried out on eight hemispheres of brains of adults from 36
      to 48 years old died in accidents without visible signs of central nervous system
      diseases. Vascular network of auditory areas is characterised by very dense
      capillary network of the third vascular layer which is the densest one in these
      areas. The vascular network of the anterior part of the superior temporal gyrus
      is distinguished by equal density of the third and fourth vascular layer.
      Fountain-like arteries are mostly of type A3 and A4 and have been found in all
      parts of the superior temporal gyrus. Vertical functional units of the cortex are
      supplied by a number of precapillary arterioles being arranged in the shape of a
      ring. In the center of each unit there is postcapillary venule through which it
      is drained.

PMID- 7739424
TI  - [Dissecting aortic aneurysms].
AB  - 33 autopsy cases of dissecting aneurysms of aorta were analyzed to find out the
      frequency, localization, macroscopic appearance, histological changes and causes
      of death. On the basis of disturbed appearance and orientation of elastic
      muscular elements of tunica media aortae, existing cystic spaces, areas of
      fibrosis and increase of mucoid basic substance in media as well as the severity
      of atherosclerotic changes, we classified our cases into familiar morentities
      which are connected with the origin of dissecting aneurysms of aorta (cystic
      medionecrosis, "noninflammatory aortopathy", atherosclerosis hypoplasia). In the
      third part of all cases media aortae contains areas similar to those of infarct,
      which could, considering the absence of cellular reaction, be corresponding with
      ischemic phenomena which directly preceded the genesis of dissection of aorta.

PMID- 7739425
TI  - [Use of radionuclide quantitative analysis in routine diagnosis of metabolic bone
      diseases].
AB  - Global and regional quantity indexes of metabolic bone activities are determined
      on the basis of given scintigraphic dose for skeleton examination. The
      calculation of all analyzed indexes was carried out in all cases of the control
      group and patients with established disturbance of bone tissue metabolism. When
      choosing the method used in the routine work, apart from diagnostic value of
      analysis numerous criteria have been respected. The analyzed global quantity
      indexes of metabolic bone activity adapted to conditions of routine work have
      similar diagnostic value, while the best regional index relating bone soft tissue
      is the one concerned with the upper leg. As the examined quantity indexes enable
      more reliable interpretation of the scintigraphic findings, in everyday work the
      scintigraphic examination should be filled in by determination of corrected
      retention of activity in the whole body and calculation of radiosotope analysis
      significantly depend one the kidney function and urine elimination.

PMID- 7739426
TI  - [Incidence of insulin-dependent diabetes mellitus in the population of Belgrade,
      0-19 years of age, from 1990 to 1992].
AB  - The data on insulin-dependent diabetes mellitus incidence in the population of
      Belgrade from the age of 0 to 19 have been gathered retrogradely. Two sources of
      data were used: hospital documentation and Registers for diabetics. During the
      period 1990-1992, 99 persons got sick of insulin-dependent diabetes while
      possibility includes 95.05% newly sick. The average rates of incidence,
      standardized according to the age distribution in the world population were
      9.7/10000 (95% the confidence interval 6.5-14.0) for the age from 0-14 and 8.4
      (95% confidence interval 5.8-11.8) for the age 0-19. The rates were highest from
      the age of 5-9 and 10 to 14. The relation of rates between sexes approximately
      equals one, but according to the age, differences between sexes were expressed.
      In females the highest rates of incidence were recorded at the age of 5, 7 and 8
      and in males at the age of 7, 11 and 12. According to the results of this
      investigation, Belgrade belongs to areas with averagely high rates of incidence
      concerning insulin-dependent diabetes.

PMID- 7739427
TI  - [Distribution of hand laterality in preschool-age children].
AB  - Laterality means functional dominance of one in the pair of organs. It represents
      the external manifestation of integrative activity of cerebral cortex meaning the
      domination of functionally dominant hand; the usability lateralization depends on
      the domination of cerebral hemisphere of gestural lateralization and the
      domination of cerebral hemisphere or gestural lateralization and the influence of
      the environment. On the basis of laterality population is divided into right
      handed and left-handed with a very stressed degree of lateralization and those
      undecided with a minimal previal of handidness of one hand. In most people the
      domination of cerebral hemisphere is average or weak and that's the reason why
      the influence of the environment is of importance when forming the dominant hand.
      In the clinical practice the hand laterality is used as an index for the type and
      degree of cerebral hemisphere domination, for condition of gestural laterality
      with the usability of the dominant hand and form the differentiation of the
      dominant hand in the case of minimal difference in handidness.

PMID- 7739428
TI  - [Cardiac microangiopathy in diabetics].
AB  - Diabetes mellitus induces microvascular damage within the myocardium, without
      coexistent changes in the extramural coronary arteries. Nonenzymatic
      glucosylation forms the biochemical basis of diabetic microangiopathy, which
      further causes specific structural changes of the heart muscle. These changes
      increase left ventricular stiffness and lead to diastolic filling abnormalities,
      that may be the first sign of diabetic cardiomyopathy. In this review the author
      discusses the pathogenesis of the microangiopathy of the heart in diabetes and
      the methods of its early detection.

PMID- 7739429
TI  - [Motivations for parenthood in infertile women].
AB  - A poll was conducted among 50 primary sterile women, 50 secondary sterile women
      and 70 fertile women, to question their motivation for parenthood, with
      assumption that innate "maternal instinct" does not exist, but that the wish to
      have a child is socially conditioned and it might differ in women having children
      and those without them. According to the gathered results it can be said that the
      fatalistic motivation for parenthood ("reproduction is the fate of every person")
      is more expressed in fertile women than in sterile ones, while the instrumental
      motivation (the child is there to enable achieving certain aims, not narcisistic)
      is more expressed in sterile that in fertile women. Primary sterile women wish to
      have a child for themselves, without concrete reasons being the main initiators
      for the beginning of sterility treatment, while secondary sterile women,
      especially those who already have one child, consider family and marriage
      incomplete without children and in the latter the husbands are usually initiators
      for the beginning of sterility treatment or the wish is mutual. However, the
      altruistic motivation for parenthood is the first and most important for all
      three groups of women (affection for children, a wish to protect them).

PMID- 7739430
TI  - [Regulation of intraocular pressure using argon laser trabeculoplasty in various
      forms of open-angle glaucoma].
AB  - Argon laser trabeculoplasty was applied in 43 patients, 46 eyes. 34 eyes had had
      primary open-angle glaucoma, while 12 eyes had secondary open-angle glaucoma
      where no compensation of intraocular pressure was achieved although maximal
      medical therapy was conducted. Applying argon laser trabeculoplasty the
      intraocular pressure was normalized in 86% of eyes with a primary glaucoma
      considering period of 18.31 +/- 2.80 months. In 58.4% of eyes with secondary
      glaucoma satisfactory reduction of intraocular pressure was achieved considering
      period of 14.57 +/- 7.91 month.

PMID- 7739431
TI  - [Epidemiologic characteristics of mortality in cancer of the tongue in
      Yugoslavia].
AB  - The paper contains mortality data about tongue cancer in Yugoslavia for the
      period from 1969 to 1988. Using descriptive epidemiologic method a demographic
      analysis was conducted on deceased from tongue cancer according to age and sex.
      The chronologic analysis includes the period of 20 years, while the topographic
      distribution of deceased includes six Yugoslav republics. Statistic models for
      studying standard mortality rates were used according the method of direct
      standardization as well as the specific mortality rates concerned with sex and
      age, equation of linear trend and proportion. The results of investigation show
      that the average standardized mortality rate concerning tongue cancer from 1969
      to 1988 in Yugoslavia amounted to 0.62 in 100,000 inhabitants. These rates are
      considerably higher in males (1.17%ooo) than in females (0.17%ooo). The specific
      rates of mortality considering age continually grow with the increase of age.
      They are relatively low, up to the age of 44 (males), and up to 54 (females). The
      examination of epidemiologic situation concerning tongue cancer in our country on
      the basis of total mortality trend (y = 0.62 + 0.03x) indicates a slow growth, in
      males (y = 0.17 + 0.07x) as well as in females (y = 0.17 + 0.01x), which points
      to a need for research of possible risk factors and prompt realization of
      adequate preventive measures.

PMID- 7739432
TI  - [Total abdominal colectomy in treatment of acute malignant obstruction of the
      left colon].
AB  - This paper deals with an experience of a total abdominal colectomy in acute
      malignant obstruction of the left sided colon. Ten patients were treated with
      total abdominal colectomy during 1991 with a high frequency of synchronous
      carcinoma (in two patients) and precancerous lesions (a big polyp in one patient)
      in total 30%. One patient died after the treatment (10%) and a complete
      dehiscence of the ileo-rectal anastomosis and reoperation on the ninth
      postoperative day. One patient had had an infection of the wound. Total abdominal
      colectomy is an operation which can have an important role in decreasing
      malignant reoccurrence, avoiding stoma in the postoperative period of one month
      in most patients. Absolute indication for total abdominal colectomy in patients
      with acute malignant obstruction of the left sided colon is the "closed loop"
      obstruction with a decompensated colon, as well as the factor of heredity in
      close relatives and the absence of locally spread tumors and metasthases
      disregarding the age of the patient and the competence of the ileocecal valvula.

PMID- 7739433
TI  - [The work of the Serbian Medical Society--the Medical Society of Vojvodina under
      present conditions].
AB  - The content of work of medical society in Vojvodina has always been primarily set
      by the founder with its main goal: the physicians professional and scientific
      specialization. In recent years there have been many socio-political, moral and
      social changes which have had great influence on the work of medical
      organizations. The poverty of the whole society, especially of the health
      service, has completely disabled organization of big professional meeting so that
      the professional activity meant mostly one-day meetings in health institutions.
      Although there was a threatening possibility to stop publishing the professional
      journal "Medical Review" after 47 years of appearing in print, today problem is
      solved by financial help by the government. Apart from professional work, other
      activities of physicians organizations are becoming important today. An
      appropriate attitude toward war generally speaking was declared in 1992 as an
      "Appeal for Peace". A request was made to distinguish profession and politics in
      the work of physicians so that the society acted only as a professional
      organization without political involvement and there is an initiative to found a
      medical association. Physicians gave their best in this hard situation to
      maintain work of the health service, but as it was not possible any more at one
      moment, an extra congress of physicians of Serbia was organized verifying serious
      consequences of war considering the health of the whole population. Society has
      been extremely engaged in solving numerous problems of ethics which have appeared
      due to war such as lack of medicines and health care materials as well as abuse
      of the private medical practice.

PMID- 7739434
TI  - [Intravenous immunoglobulin in the treatment of infections in children with acute
      leukemias].
AB  - Infections are a common cause of complications in the course of applying highly
      aggressive combined cytotoxic therapy in children suffering from acute leukemias
      (ALL and ANLL). The effect of adjuvant therapy of intravenous immunoglobulins
      (IVIG) was investigated in cases of infections of children with ALL and ANLL (24
      with IVIG and 24 without this therapy) according to the system of matched pairs.
      The polyvalent functionally intact monomeric i.v. immunoglobulin "Endobulin"
      Immuno, 100 mg/kg was applied in infections--febrile episodes combined, if
      possible, with an aimed antibiotic therapy. It was established that children with
      the intravenous immunoglobulin therapy had had statistically significantly less
      febrile episodes (p < 0.01), as well as less febrile days (p < 0.05). Although
      the acquired results speak in favor of this therapeutic possibility when applying
      this supportive therapy which is getting more and more important, authors made a
      conclusion that the final estimate of the value of this therapy remains open and
      requires further investigations.

PMID- 7739435
TI  - [Motivation in patients for surgical treatment of prognathism using bimaxillary
      surgery].
AB  - A postoperative survey was conducted to evaluate the motivation of twenty three
      patients following surgical correction of mandibular prognathism. The operative
      technique of bimaxillary surgery was applied to all patients. The major reason
      for surgery was esthetics. Majority of patients were informed about surgery by
      their family dentists, and almost all of them were satisfied and stated that
      their expectations were fulfilled.

PMID- 7739436
TI  - [Fracture of a transfixed intramedullary nail in a patient with pseudoarthrosis
      of the femoral diaphysis].
AB  - This is a case report on a patient with a multiple femur's fracture where a
      transfixed intramedullar nailing of Grosse-Kempf type has been done. "The nail
      dynamization" was not carried out before the beginning of vertical loading. Seven
      months after the full vertical loading had begun, at a sudden torsian movement of
      the extremity, the nail had broken. Analyzing the cause of the fixative material
      fracture, a conclusion has been made that, apart from the presence of adequate
      trauma, the nail fracture happened also due to the development of pseudoarthrosis
      of femur and the unfulfilled "nail dynamization".

PMID- 7739437
TI  - [Leber's optic atrophy (case report of progressive hereditary amaurosis].
AB  - This paper presents clinical findings of Leber's optic atrophy, a hereditary
      disorder, characterized by a progressive lost of vision. It points out to the
      validity of complex clinical, laboratory and neurophysiological investigations
      and excludes other diseases which by differential diagnosis may be taken into
      account.

PMID- 7739438
TI  - [Modern psychosomatic aspects of dermatology].
AB  - Concerning their origin most diseases are multifactorial and that goes for skin
      diseases too. Emphasizing just one must not exclude further research and other
      aspects of etiopathogenetic mechanisms. It has been known for along time that
      psychological factors have a certain influence on the start, aggravation and
      maintenance on skin changes and that cosmetic defects of this kind disturb the
      psychological peace of the sick person and his capacity of establishing
      satisfactory social relations. Psychosomatic approach in dermatology cannot be
      reduced to investigation of specific etiology in the field of psyche without
      physical or social spheres. It unites all of them and in that way the old
      question what cause and what the consequence is has no importance, because there
      is no time or distance limit among them. They act simultaneously, holistically.

PMID- 7739440
TI  - [Partial laryngectomies].
AB  - After introduction of partial laryngectomies into the treatment of malignant
      larynx tumors, within a research project we analyzed symptoms, occurrence and the
      type of partial larynx resections for the two year period (October 1990 to
      September 1992). During this period of time 111 patients with malignant tumors
      were operated, while total laryngectomy was performed in 50 (45.0%).
      Laryngomicroscopy was performed in 14 patients (12.6%), and in 47 patients
      (42.3%) one of the partial resections of larynx was performed. Horizontal
      laryngectomy was performed in 25 patients (22.5%), while one of the vertical
      laryngectomies in 22 patients (19.8%). Concerning horizontal laryngectomies the
      following were performed: horizontal glossectomy, horizontal supraglottic
      laryngectomy and horizontal supraglottic laryngectomy spread to the tongue base,
      arytenoid and vocal cord. Concerning vertical laryngectomies the following were
      performed: hordectomy, frontal, frontolateral laryngectomy, vertical laryngectomy
      and hemilaryngectomy.

PMID- 7739439
TI  - [The value of local administration of antibiotics in treatment of bone
      infections].
AB  - An open, controlled, randomized clinical investigation was carried out in 33
      patients suffering from osteomyelitis. In the first group, 17 patients, a through
      drainage with sterile physiologic solution was applied, while in the second
      group, 16 patients, antibiotic was added to the sterile physiologic solution. In
      all patients values of C reactive protein (CRP) in the blood were examined, and
      later on every third day after the operation. A significant difference of average
      values of CRP between the 3rd and 21st day in both groups of patients was
      established, as well as the similarity in average values of CRP, which points to
      the fact that the mechanical effect of through drainage is dominant, speaking
      about rinsing focus of infection and eliminating necrotic tissues and small
      sequesters.

PMID- 7739442
TI  - [Epidemiologic importance of gallbladder neoplasms in Belgrade].
AB  - The average standardized mortality rate caused by gallbladder neoplasms in
      Belgrade during the period from 1975 to 1990 amounted to 2.8 in 100,000
      inhabitants. It was much higher in women -3.5/10000 than in men--1.9/10000.
      Considering specific age mortality rates they show low values for people to 54
      years of age, and then an abrupt increase happens with the highest values
      recorded in the oldest group. Mortality trend caused by gallbladder neoplasms
      examined during these 16 years at this territory shows growth (y = 1.37 + 0.17x)
      which is more expressed in females (y = 1.46 + 0.24x) than in males (y = 1.35 +
      0.07x).

PMID- 7739441
TI  - [The effect of hypertension on prolactin levels in pregnant women at term].
AB  - In 79 women with regular menstrual cycle and giving birth to children on the
      274th to 287th day of gestational age, prolactin was determined in mother's
      serum, umbilical artery serum and in the amniotic fluid, by using radioimmunity
      method in mg/l. Two groups of women and their newborn infants were examined. In
      the first group (n - 36) were women with hypertension, in the second (n - 43)
      healthy women. The average values of prolactin (X +/- SD) in mother's serum
      (214.3 +/- 98.6 micrograms/l and 189.4 +/- 94.7 micrograms/l) in examined women
      do not differ significantly (p > 0.05). The level of prolactin in the serum of
      embryo is much higher (p < 0.01) in women with hypertension (338.2 +/- 106.5
      micrograms/l) than it is the case in normal pregnancies (251.6 +/- 99.2
      micrograms/l). The values of prolactin are significantly higher (p < 0.01) in the
      amniotic fluid in women from the examined group (527.3 +/- 188.6 micrograms/l)
      than in the control group (398.1 +/- 156.3 micrograms/l). The difference between
      the level of prolactin in the amniotic fluid of women with meconium and clear
      amniotic fluid in both examined groups is not significant (p > 0.05). Values of
      correlation coefficient are small (r < 0.317) and point that the mutual
      dependence among the prolactin in mother's serum, umbilical artery serum and
      serum of the amniotic fluid is not significant.

PMID- 7739443
TI  - [Facial nerve lesions in gunshot injuries of the temporofacial region].
AB  - Experiences and difficulties in the preoperative diagnostics and treatment of
      facial nerve lesions concerning nine injuries of the temporofacial region caused
      by firearms projectiles are presented. Otosurgery treatment of the damaged nerve
      occurred from the 8th to 22nd day, after the vital functions normalization and
      taking care of maxillofacial region injuries. Apart from facial nerve paralysis,
      in 7 injured cophosis occurred, but immediately after they had been injured all
      had vertiginous disorders. Before detecting the place of the nerve lesion
      complete skeletization of the fallopian tube was done. Since in four cases there
      was a complete disconnection of the facial nerve distally from stylomastoid
      foramen, authors point to the importance of nerve exploration in this segment. In
      all cases development of connective tissue was expressed just like granulation of
      mastoid cells and cavum, and in 4 injured there are clear signs of infection at
      the place of nerve lesion, so that there is a need to perform the operation as
      early as possible.

PMID- 7739445
TI  - [Addison's disease].
AB  - This is a report on a patient 57 years old, hospitalized because of expressed
      fatigue, nausea, vomiting and epigastrium pain. Hyperpigmentation of skin and
      mucous and hypotension were present; and hypocorticism was suspected while ex
      iuvantibus substitutional therapy of corticosteroides was introduced. By testing
      thyroid gland function, hypothyroidism was established, so we suspected the
      presence of united pluriglandular insufficiency--Schmidt Syndrome. The patient
      reacted well to the substitutional therapy of hydrocortisone and levothyroxine.
      The diagnosis has been confirmed at the Clinic for Endocrinology in Novi Sad and
      today the patient has regular checks at the outpatients clinic for endocrinology
      in Sombor. The discussion contains important diagnostic and therapeutic problems.

PMID- 7739444
TI  - [Dissecting aortic aneurysm as a cause of fever of unknown origin].
AB  - Dissecting aortic aneurysm is a clinical syndrome commonly with a dramatic course
      and a fatal prognosis. The disease often has a fatal ending at the very
      beginning, a few hours after the onset. High temperature happens sometimes, but
      is rarely a dominant symptom. We presented a case of a patient with a long term
      febrile state caused by dissecting aortic aneurysm, where pleuropneumenia covered
      the real nature of the disease. It has been pointed out that dissecting of aorta
      should be thought of in patients with unclear febrile states, especially if they
      have difficulties in the area of thorax.

PMID- 7739446
TI  - [Masters of obstetrics in the area of Vojvodina in the 18th and 19th century].
AB  - The author reviews data about masters of obstetrics, physicians and surgeons
      nonphysicians, who worked in Vojvodina from the second half of the 18th till the
      beginning of the 20th century. They used to be the professional and time bridge
      as well as extremely important developmental link of continuity between the
      obstetrics of untrained and subsequently educated midwives and physicians gyneco-
      surgeons, later specialists gynecologists--obstetricians all as a part of
      integral discipline of gynecology and obstetrics in the area of Vojvodina. The
      existence of about 30 masters of obstetrics in the area of today's Vojvodina from
      the 18th to the 20th century, educated at medical faculties of Vienna, Budapest
      and Graz, points to the fact that obstetrics and gynecology in our regions in the
      18th and especially 19th and 20th centuries, used to have similar, and somewhere
      identical trends and directions of development, like the obstetrics and
      gynecology of Central Europe of that time and that it used to be, just like it is
      today, a part of European gynecology and obstetrics.

PMID- 7739447
TI  - [Desirable ways of reforming the health care system in Yugoslavia].

PMID- 7739448
TI  - [Serotonin immunoreactivity in the adrenal medullar in hypoxia].
AB  - Laboratory rats were exposed to influence of intermittent hypoxia every other day
      during the period of 11 days. Conditions similar to those of 7000 meters above
      sea level were imitated. Using the method of indirect immunofluorescence the
      state of serotonin immunoreactivity of the adrenal glands medulla was analyzed.
      After exposure of animals to influence of hypoxia serotonin decreased in the
      adrenal glands medulla, which is in harmony with the realization concerning
      adrenomedullar regulatory mechanisms as a response to hypoxia.

PMID- 7739449
TI  - [Levels of beta-endorphins in peripheral blood plasma in infertile women with and
      without symptoms of hyperandrogenism].
AB  - In 56 infertile women, aged 20 to 35, beta-endorphin (beta-EP) was determined out
      of the sample of peripheral blood plasma as well as the serum testosterone (T),
      progesterone (Prg), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), sex
      hormone binding globulin (SHBG) at the medium (from the 6th to 9th day) and at
      the late follicular stage of the menstrual cycle (from the 10th to 14th day), the
      early luteal stage (from the 15th to 19th day) and at the late luteal stage of
      the cycle (from the 20th to 25th day). According to the gathered results of T,
      DHEA-S and the evaluated indexes of free androgenes of--FAI, women were grouped
      into two groups. Those with hyperandrogenism (n = 30) and those without
      hyperandrogenism (n = 26), with two subgroups: those with ovulation and those
      without it. Women with ovulation and without hyperandrogenism showed
      statistically significant higher concentration of beta-EP at the late luteal
      stage of the cycle in comparison with those without ovulation belonging to the
      same group (n = 9; 5.5 +/- 1.4 vs n = 7; 3.5 +/- 0.6; p < 0.01) as well as
      concerning the early luteal stage of their own cycle (5.5 +/- 1.4 vs 4.3 +/- 0.3;
      p < 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7739451
TI  - [Zoonoses in Vojvodina. I. Epidemiologic characteristics of tetanus in
      Vojvodina].
AB  - Epidemiologic characteristics of tetanus in Voivodina were analyzed on the basis
      of reported cases of sickness or death, during the period from 1962 to 1991, and
      epidemiologic investigation on 35 sick persons suffering from tetanus during the
      last 5 years. By compulsory immunization against tetanus this disease is
      practically eliminated at the age when one is protected by immunity vaccine.
      Abandoning domiciliary childbirth neonatorum tetanus has been eliminated. Today
      tetanus occurs sporadically as a result of small, naive injuries, mostly in
      nonimmunized elderly people. Considering number of the sick, in 6.1% it happens
      to persons older than 60 years of age. Tetanus remains a health problem because
      of its high lethality, which is statistically significantly higher in older
      patients. On the basis of gathered results it is realistic to expect that
      applying compulsory immunization against tetanus to older people in 10 year
      intervals will not eliminate this disease, but it will significantly reduce
      lethality which is still about 25% in Voivodina.

PMID- 7739450
TI  - [Distribution of macroscopic determination of narrowing of the lumen of coronary
      arteries in ischemic heart disease].
AB  - The paper presents macroscopically analyzed 2600 segments 0.5 cm of length of all
      three main coronary arteries in 50 consecutive autopsy cases suffering from
      ischemic (coronary) heart disease. A quarter of segments had had a "critical"
      lumen narrowness (75% of more). The greatest concentration of "critical" lumen
      narrowness is within the first 6 cm of length. Similar distribution of "critical"
      lumen narrownesses was found in the first 4 cm of length of circumflex branch of
      left coronary artery with a remark that concentration of examined segments was
      higher between the second and fourth cm. The greatest concentration of "critical"
      lumen narrownesses was not established, because these segments are evenly
      arranged along the first 10 cm, when examined according to the assumed thirds.
      Single coronary disease was found in 10% of cases, double coronary disease in
      44%, triple coronary in 44% and stenosis of the left coronary arteries in 2%. On
      the average 2.3 coronary arteries with "critical" lumen narrownesses were found
      in each case.

PMID- 7739453
TI  - [Diseases of the respiratory organs on the threshold of the 3rd millenium of a
      new era. Pneumophthisiologic-pulmonary perspectives].

PMID- 7739454
TI  - [Immunoreactivity in the adrenal medulla in hypoxia].
AB  - Laboratory rats were exposed to influence of intermittent hypoxia every other day
      during the period of 11 days. Conditions similar to those of 7000 meters above
      sea level were imitated. Using the method of indirect immunofluorescence the
      state of noradrenal, adrenal and serotonin immunoreactivity of adrenal glands
      medulla were analyzed. After exposure of animals to influence of hypoxia
      adrenalin and serotonin are decreased in adrenal glands medulla, while noradrenal
      cells get totally emptied. The decrease of adrenal and noradrenal contents in the
      adrenal glands is in harmony with the knowledge about involvement of
      sympathoadrenal regulatory mechanisms as a response to hypoxia. The finding of
      decreased serotonin is explained by its simultaneous release with adrenalin from
      of adrenal glands medulla.

PMID- 7739452
TI  - [Biologic stress: possible role in the pathogenesis of depression].
AB  - This paper presents a review of biologic mechanisms of stress and analyzes their
      role in the pathogenesis of depressive disorder. Recent investigations point to
      the fact that apart from hereditary predisposition in the pathogenesis of
      depression different biologic mechanisms, included into the regulation of
      organism response to stress, have an important role. These findings are in
      harmony with the well known fact from the clinical practice, that exposure to
      stressor may lead to depression in persons who do not normally react
      depressively. The newest findings point out the significance of biologic
      mechanisms of stress which exert influence on a person at the early neonatal
      period, even before that, during the embryonal development. However, on the other
      hand in humans it is very probable that mechanisms, included into the regulation
      of response of the organism to stress, are important for the homeostasis of
      emotions and willing--instinctive dynamisms, and indirectly for the cognitive
      functions, as well as for maintaining harmony among these dimensions of psychic
      existence and demands of the external--physical, biologic and social-
      environment.

PMID- 7739455
TI  - [Specific inflammatory processes in collagenosis, degenerative and malignant
      diseases of the skin of the face and neck during aging].
AB  - 214 skin lesions have been analyzed in the paper and 158 cases of Carcinoma
      basocellulare, 22 cases of Carcinoma planocellulare and 11 cases of melanoma were
      registered. Concerning localization it has been established that skin of the face
      is mostly endangered both for malignant and benign lesions. In 10 cases Keratosis
      senilis, a benign kind of lesion, was diagnosed, Dermatitis post irradiationem
      was diagnosed in 8 cases and Lupus erythematodus in 5 cases. By histologic
      analysis the following can be stated: if the degree of degradation and damage of
      collagen fibers is high, the intensity of lymphoplasm infiltrate density and
      intensity of mastocyte cells density is reduced. If the degree of decomposition
      of collagen fibers is lower, the lymphoplasmocyte infiltrates are denser as in
      the stroma of the lesion as well in edges and in the surrounding dermis. Changes
      were primarily found in malignant skin lesions, but they are identical in cases
      of keratosis senilis as a premalignant lesion. However, concerning nonmalignant
      lesions, depending on exterior factors, long time influence of noxa, collagen
      fibers and their degree of degradation have an important role in the cell
      interaction, and more attention should be paid to exploring decomposition of
      collagen fibers as components of the local immunobiologic reaction of the
      organism to lesion formation.

PMID- 7739456
TI  - [Zoonoses in Vojvodina. II. Epidemiologic characteristics of leptospirosis in
      Vojvodina].
AB  - On the basis of reported cases of sickness--death due to leptospirosis and the
      epidemiologic investigation of 38 sick individuals, epidemiologic characteristics
      of anthropozoonosis in Vojvodina were analyzed. It has been established that this
      disease is registered in the form of individual cases, mostly in persons
      belonging to the productive population. Infection usually happens during the
      summer months and due to contact with contaminated water. High lethality and
      antibodies of leptospirosis icterohaemorrhagiae in 55.3% of samples of the serum
      of the sick point to the fact that only clinically severe forms of the disease
      were registered.

PMID- 7739457
TI  - [Association of autonomic neuropathies and gastrointestinal peptides in non
      insulin dependent diabetics].
AB  - Basal and postprandial levels of gastrin, somatostatin, vasoactive intestinal
      polypeptide (VIP) and pancreatic polypeptide (PP) were followed up in 105
      patients with non insulin dependent diabetes mellitus (20 with autonomic
      neuropathy only, 35 with peripheric neuropathy only, 30 with autonomic and
      peripheric neuropathy simultaneously and 20 without any sign of neuropathy) and
      in the control group of 40 individuals. Serum levels of gastrin, somatostatin,
      VIP and PP are determined by a RIA (used kits of Prof. SR Bloom, Hammersmith
      Hospital, London). The results of investigation showed significantly higher basal
      and postprandial levels of gastrin and VIP in patients with autonomic neuropathy
      in comparison with the group without neuropathy and with the control group (p <
      0.001). The serum levels of somatostatin did not differ significantly between the
      groups of diabetics with and without neuropathy. Basal level of PP was
      significantly lower and postprandial PP levels remained low in patients with
      autonomic neuropathy in comparison with the group without neuropathy (p < 0.001).
      We postulate that basal and postprandial gastrin and VIP levels raised secondary
      to partial vagotomy in diabetics with autonomic neuropathy. Measuring PP serum
      levels in diabetics after a protein rich meal can be useful to check vagus nerve
      function in the gastrointestinal tract in order to detect autonomic neuropathy.

PMID- 7739458
TI  - [Alcohol and the liver. Present knowledge of pathogenic mechanisms].
AB  - Intensive longtime experimental and clinically-experimental investigations have
      not yet succeeded unriddling the intimate mechanism of liver alcoholic damage.
      Earlier knowledge on accumulation of fats in liver under the influence of alcohol
      (ethanol) is still actual, but it probably represents only epiphenomenon and does
      not explain the intimate mechanism of events. It still can be stated that,
      although the aim has not been achieved, gradually, as a consequence of very
      studious investigations we have signification information which bring more light
      in regard to identify the mechanism of this frequent disease of modern mankind.
      We have tried to summarize the latest knowledge on alcoholic liver damages.
      However, some of the most simple questions still do not have an answer: why do,
      for example, some longtime alcoholics, whose everyday intake of alcohol is big,
      develop liver cirrhosis at the end of their lives, while the others, under the
      same circumstances, develop it very early?

PMID- 7739459
TI  - [Laparoscopic cholecystectomy].
AB  - The author presents a new surgical procedure-laparoscopic cholecystectomy.
      Comparing the time interval from introduction to widespread adaption of other new
      operations this century, such as vagotomy and open cardiac procedures, it took
      remarkably little time for the surgical community to accept laparoscopic
      cholecystectomy. To perform endoscopic surgery, surgeons had to improve eye-hand
      coordination, adapt to a new tactile sensation and lack of depth perception. The
      laparoscopic cholecystectomy is "here to stay". The author reports
      preintervention program as well as the procedure and its technique with necessary
      instruments. Laparoscopic cholecystectomy is a recently developed alternative to
      open cholecystectomy that is rapidly gaining popularity because patients have
      experienced reduced stay in hospital, decreased wound pain and early return to
      normal activity.

PMID- 7739460
TI  - [Transplantation of allogenic bone marrow in the first remission in acute
      nonlymphoblastic leukosis: ethical risks].
AB  - Allogenic bone marrow transplantation is a choice therapy in consolidation of the
      first remission of acute nonlymphoblastic leucosis. Absolute confidence in this
      therapeutic procedure where high lethality of patients is present is ethically
      risky. The basic ethical risks are: real possibility to perform transplantation
      in potentially healthy persons in whom leukosis was eradicated by previous
      cytostatic therapy and the fact that results of allogenic bone marrow
      transplantation stagnate, while the competing forms of treatment as chemotherapy
      and transplantation of autologous hematopoietic cells get improved from day to
      day. The degree of confidence in the allogenic bone marrow transplantation
      exceeds quality and results of clinical studies on which it is based. The ethical
      risk of transplantation is higher if the donor is a woman and the recipient is a
      man, one-egg twins, HLA-identical non related or HLA-nonidentical related
      persons. Analysis of clinical studies showed that absolute confidence in
      allogenic bone marrow transplantation in the first remission of acute
      nonlymphoblastic leukosis has no valid foundation. Individualization of
      postinductional therapy would reduce ethical risks and improve results of
      allogenic bone marrow transplantation.

PMID- 7739461
TI  - [Motor organization in children with encopresis].
AB  - The paper reviews the degree of fecal retention in regard to organization of
      certain functions of central nervous system (motoric, vegetative and psychic), as
      well as to certain qualities of motoric organization by means of correlation
      analysis. Gathered results point to connection between poor tonic organization,
      especially of the axial muscle tonus and neuromuscular binds and the degree of
      fecal retention; correlations are positive, linear, so that poor motoric
      organization can be considered basic for the disorder of the pelvic floor muscles
      function and consequent encopresis.

PMID- 7739462
TI  - [Phagocytic activity of polymorphonuclear cells in patients with psoriasis
      vulgaris from the aspect of PUVA therapy].
AB  - The authors present results of examining phagocytotic activity of
      polymorphonuclear (PMN) granulocytes in patients with psoriasis vulgaris from the
      aspect of applied PUVA-therapy. 100 patients with psoriasis vulgaris were
      examined and divided into three groups, 20 patients with acute exanthematous form
      of the disease, 16 patients with chronic stationary form of the disease, and 64
      patients with acute phase of the chronic form of the disease. 50 healthy persons
      made up the control group. Phagocytotic activity of neutrophils was examined by
      opsonization test, a modified method by Brandt. Phagocytotic index was expressed
      as a number of ingested particles of yeast germs in 100 PMN. Polymorphonuclears
      of patients were examined in the autologous and control serum of healthy people.
      Values of immunoglobulin IgM and IgG as well as values of complement C3 were
      examined in all patients using the method of laser nephelometry (Behring). All
      mentioned parameters were determined prior to and after PUVA therapy which was
      conducted by apparatus: PUVA 4000 and 6001. Results of examination show that the
      phagocytotic activity of PMN in patients with psoriasis vulgaris is normal and
      that it does not depend on how skin disorders are spread, on the strength of
      infiltration, exudation, the length of duration and course of the disease, as
      well as on applied PUVA-therapy. Reduced phagocytotic activity of PMN was
      determined only in individual cases, that is in 5 patients not depending on the
      applied therapy. In one patient hypoimmunoglobulinemia IgM as a probable cause of
      disturbed phagocytosis was established while in the remaining 4 patients causes
      of reduced phagocytosis remained unknown.

PMID- 7739463
TI  - [Recurrence around tracheostomies: analysis of risk factors].
AB  - 302 patients with planocellular larynx carcinoma treated by total laryngectomy
      during the period from 1975 to 1986 were analyzed. In the examined group of
      patients significant risk factors in tracheostoma relapse appearance were the
      next: glottis-subglottis tumor localization and regionally spread tumor. Planned
      postoperative radiotherapy can significantly reduce the risk of tracheostoma
      local relapses' appearance.

PMID- 7739464
TI  - [Dynamic thermoplastic cervico-thoracic orthoses in conservative and
      postoperative treatment of congenital torticollis].
AB  - Contention of the corrected position of the rotation and anteflexion of the head
      and neck is very important for the congenital torticollis. Frequent reversion of
      the deformity was the consequence of the unproper passive and static cast
      bandages or rigid plastic and more functional leather-metal orthosis. Original
      dynamic cervico-thoracic orthosis, made of thermoplastic material, provides
      progressive, individual and stable correction and contetion of the best possible
      head and neck position. The value of the applied orthosis is proved by the
      excellent results in treatment of 12 non-operated children and 16 postoperative
      treated children that suffered of primary myogenic torticollis.

PMID- 7739465
TI  - [Occurrence of diabetes mellitus in the Kovin District].
AB  - According to its epidemiologic diffusion diabetes, as a massive disease,
      represents not only a medical, but also a social problem. Apart from that, it
      presents one of the main risk factors in developing cardiovascular diseases which
      are the leading cause of mortality. In Kovin municipality, at the counseling
      service for diabetes, 800 diabetics are registered, which means 2% of the
      inhabitants (39840). 200 patients were chosen for analysis, that is every fourth
      patient. According to results of the investigation, there were 133 women (66.5%),
      and 67 men (33.5%). According to their age, 94 patients (47%) were 60 years old
      or older, and 78 patients from 50-59 years of age (39%).

PMID- 7739466
TI  - [Use of nuclear medicine technology (radionuclide venography) in detecting a case
      of suspected ileofemoral phlebothrombosis].
AB  - We reviewed a complex nuclear medical method's application for investigating
      venous circulation of lower extremities--radionuclide venography (RVG) in
      explaining a case of suspective ileofemoral thrombosis. Suffering from pain and
      swelling of the right leg, patient T.J. wanted a checkup. After the physical
      examination, vascular surgeon suspected phlebothrombosis of the right ileofemoral
      region and immediately sent her to have a radionuclide venography (RVG) (because
      by Doppler-ultrasonography certain data confirming presence of thrombus in the
      pelvic region couldn't be gained). On the basis of gathered results vascular
      surgeon can make a final diagnosis (phlebothrombosis of the right vein
      femoralis), so that in this case flebography was not necessary. Although
      performing RVG is complex and requires engagement of experts of different
      profiles, gathered data are valuable because they cover the shortage of existing
      diagnostic methods which are most often used in routine work (Doppler
      ultrasonography and phlebography). Applying RVG phlebography can be avoided in
      all patients who are not expected to have operative treatment, and in cases where
      thrombosis is suspected in deep veins of pelvis, RVG can be performed right away,
      without Doppler ultrasonography.

PMID- 7739467
TI  - [The hyperventilation syndrome in children].
AB  - Hyperventilation syndrome is not a rare disorder present primarily in children,
      but in adolescents too. It points to anxiety in children with or without family
      problems. The clinical picture is polymorphous and often without a clear
      connection with hyperventilation. That is why it is necessary for the physician
      to be aware of this problem in practice. The diagnosis is made on the basis of
      clinical picture and hyperventilation provocative test, when one expects this
      disorder might occur. We have reported five cases of children with this syndrome,
      with a special review concerning clinical picture and the way which led to the
      confirmation of diagnosis.

PMID- 7739468
TI  - [General findings on iodine deficiency and prophylaxis in Italy].

PMID- 7739469
TI  - [In vitro effects of IL-2 on human hypophyseal adenoma].
AB  - The effects of two different concentrations of IL-2 on human pituitary adenomas
      (one secreting ACTH and one secreting GH) were evaluated in vitro. A specimen of
      the tumor was dissagregated and the cells were incubated for three days with RPMI
      1640 medium. The medium was then decanted and the cells were incubated with 1 mlo
      of fresh medium for three hours and then with new fresh medium containing two
      different concentrations of IL-2, 100U/ml, for three hours too. The pituitary
      hormones, ACTH and GH, released into the medium were assayed by RIA. Dose of 100
      U IL-2 induced a profound increase of ACTH release. The other dose decreased ACTH
      release. The release of GH was suppressed by IL-2 at the two concentrations
      tested. IL-2 may be an immunologic messenger exerting direct action at pituitary
      level. It appears probable that IL-2 plays an important role in determining the
      response of the pituitary to stress and infections.

PMID- 7739470
TI  - [Neuropsychologic symptoms of primary hyperparathyroidism in the elderly. Report
      of a clinical case].
AB  - Primary hyperparathyroidism is a not uncommon disease in the elderly. A
      prevalence of 3% for women and 1% for men is reported in subjects aged 65 years
      and over. Routine serum calcium determination and parathyroid hormone radioimmuno
      assay allow to make an early diagnosis in still asymptomatic subjects. In the
      elderly the clinical features of the disease are often aspecific presenting with
      psychiatric and/or neuromuscular and/or cardiovascular disorders. This report
      refers to a 75 year-old woman admitted to our Department with a suspicion of
      senile dementia. She was affected by loss of memory, hallucinations, nausea, loss
      of appetite, mild polydipsia and polyuria. The patient was dependent in one
      activity of daily living (Index of Independence in Activities of Daily Living,
      ADL) and partially dependent in instrumental activities of daily living
      (Instrumental Activities of Daily Living Scale, IADL). The Short Portable Mental
      Status Questionnaire (SPMSQ) and the Geriatric Depression Scale (GDS) showed mild
      mental impairment and mild depression. Routine biochemical screening revealed a
      significant hypercalcemia. Parathormon assay and parathyroid scintigram were
      performed to confirm the diagnosis of primary hyperparathyroidism. After
      treatment of dehydratation and hypercalcemia, parathyroidectomy was performed: a
      single parathyroid adenoma was found and removed. On discharge the patient was
      lucid and able to carry out all ADLs and IADLs.

PMID- 7739471
TI  - [Short-term effects of salmon calcitonin rectal administration in women with
      involutive osteoporosis].

PMID- 7739472
TI  - Tuned-in to telemedicine.

PMID- 7739473
TI  - Rural Minnesota family physicians' attitudes toward telemedicine.
AB  - This study reports the results of an assessment of the attitudes and opinions of
      rural Minnesota family physicians toward telemedicine. The results of 52 mail
      surveys and 32 telephone interviews were compiled to determine existing attitudes
      and levels of awareness concerning aspects of telemedicine. Surveyed physicians
      overwhelmingly agreed that they do not have sufficient information about
      telemedicine. Their awareness of telemedicine's applications and capabilities is
      minimal. Also, responding physicians indicated little knowledge regarding such
      important issues as cost-effectiveness, reimbursement, liability, and potential
      primary care benefits. In general, however, physicians' attitudes toward
      telemedicine were favorable. This information should be important to funders,
      suppliers, and potential users of telemedicine. This study suggests a need to
      educate medical students, residents, and practicing physicians about telemedicine
      and issues related to its use.

PMID- 7739474
TI  - Let's not forget outstate resources for Alzheimer's.

PMID- 7739475
TI  - Is Prozac really perilous?

PMID- 7739477
TI  - Can the physician-patient relationship survive?

PMID- 7739476
TI  - Health care for the uninsured in Duluth.
AB  - Providing health care for Minnesota's uninsured population continues to be both a
      clinical and political challenge. Between October 1, 1991, and September 30,
      1993, 1,260 previously uninsured people received charity health care in Duluth.
      No one was excluded because of pre-existing conditions. Their utilization of
      services and associated costs can help project the health care needs and costs of
      care for uninsured Minnesotans. This group of uninsured people used a different
      mix of health care services compared with insured Minnesotans, and their total
      costs (including prescriptions) were about 15% greater. A large proportion of
      these uninsured Minnesotans had chronic health conditions and a "pent-up need"
      for services and medications. This experience demonstrated that it is possible to
      administer a limited benefits plan in coordination with existing public and
      private resources.

PMID- 7739478
TI  - MMA opposes Medicare cuts.

PMID- 7739479
TI  - Universal coverage: policy options and the Minnesota experience.

PMID- 7739480
TI  - Tonsils may show AIDS progression.

PMID- 7739481
TI  - Lack of correlation between salivary Streptococcus mutans and lactobacilli counts
      and caries in IDDM children.
AB  - In a previous clinical study regarding the incidence of caries and the
      periodontal health, a group of young patients with various levels of glyco
      metabolic control was studied and the results showed that the decayed-missing
      filled teeth (DMFT) index was higher in insulin dependent diabetes mellitus
      (IDDM) type 1 patients with a poor glyco-metabolic balance than in a control
      group or in IDDM patients with sufficient glyco-metabolic balance. In light of
      these results, the purpose of this study was to find an explanation for these
      clinical observations by searching at a microbiological level. The results
      indicate that salivary counts of Streptococcus mutans and lactobacilli were
      higher in patients with active caries whether or not they be diabetic, than in
      people with no active caries, but the count of S. mutans was not directly
      correlated to the DMFT index. No significant alterations were found in salivary
      flow, pH, buffer capacity and glucose concentration in all the groups in this
      study. We conclude that the salivary count of S. mutans is not sufficient alone
      to account for the higher susceptibility to active caries of young IDDM patients
      with poor glyco-metabolic control.

PMID- 7739483
TI  - [The clinical evaluation of acetoxyethylcefuroxime in dentistry].
AB  - The study examines the use of an oral antibiotic with a wide spectrum of action
      tested in dentistry belonging to the cephalosporin class: acetoxyethylcefuroxime.
      The pharmaceutical industry has succeeded in synthesising a prodrug of parenteral
      cephalosporin "Metoxyrinic cefuroxime sodium", thus resolving the problems
      presented by earlier molecules such as: scarce bioavailability, poor palatability
      and collateral effects at a gastroenteric level. This is a 2nd generation
      cephalosporin whose mechanism of action consists in the capacity to selectively
      block the synthesis of the peptidoglycan, a fundamental component of the cell
      wall of both Gram+ and Gram- bacteria. The study, which was performed in the
      Division of Odontostomatology of the Mauriziano Hospital in Turin, examined 59
      patients suffering from some of the most commonplace dental pathologies such as:
      apical periodontitis-alveolitis-odontogenic abscesses-eighth teeth in
      dysodontiasis-maxillary cysts. The following clinical parameters were evaluated
      in both outpatients and those undergoing surgery: swelling, pain,
      lymphoadenopathy at the start of treatment, and at days 3 and 5 of treatment. A
      250 mg tablet was administered every 12 hours for 5 days. Owing to the rapid
      resolution of symptoms and the limited collateral effects observed, the authors
      conclude that the drug may be regarded as the elective form of treatment.

PMID- 7739482
TI  - [The advantage of the autologous parietal bone graft in posttraumatic
      rhinoplasty].
AB  - Popularized by Tessier in 1982, the calvarial bone graft has been used
      extensively in reconstructive techniques in the cranio-facial region. The authors
      present here their experience of nasal bone grafting using split skull grafts for
      post-traumatic reconstructions. Ten patients, with a total of 11 bone grafts
      harvested, were operated. Results are reported. The level of patient satisfaction
      has been high. We have had only 2 minor complications, 1 case of alopecia,
      corrected by a resection in local anesthesia, this inconvenient has never
      reported before in the literature, and another case of secondary displacement of
      the nasal bone graft, who required a second operation with a good result.
      Discussion is reported. Several methods have been used for nasal reconstruction
      as silicone implants and other bone donor site; but they have disadvantages like
      painful to the donor site, long hospitalizations, infections and extrusions, etc.
      The use of cranial graft has some advantages: first of all, it is less likely to
      resorb, because of its membranous origin, the donor site is in close proximity to
      the area to be grafted, there is almost no morbidity to the donor site. Recently
      two case reports describing major complications were published in the literature.
      A case of a superior sagittal sinus laceration reported by Cannella and Hopkins
      and a case of an intracerebral hematoma, reported by Leroy-Young. For these
      reasons it's important to follow strictly the surgical procedure described. We
      recommended this technique only to those surgeons who are experienced in cranio
      facial surgery.

PMID- 7739484
TI  - [Bone involvement of the jaws in AIDS-related Kaposi's sarcoma].
AB  - The authors report on five patients with jaw bone involvement of Kaposi's
      sarcoma. In this study clinical, radiographic and histopathological aspects are
      described.

PMID- 7739485
TI  - [Maxillofacial and dental anomalies in multiple-abnormality syndromes. The
      clinical and therapeutic aspects in Sotos' syndrome].
AB  - The authors describe the maxillo-facial and dental anomalies present in a rare
      polymalformative syndrome: Sotos' syndrome. After having examined the syndrome
      and reported a case, they propose a therapeutic approach for the treatment of
      young handicapped cooperating patients.

PMID- 7739487
TI  - [Bilateral adenolymphoma (Warthin's tumor) of the parotid. The anatomicoclinical,
      diagnostic and therapeutic aspects of 2 cases].
AB  - Cystadenoma lymphomatosum or Warthin's tumor of the parotid glands appears
      bilateral in 8-10% of cases, synchronous (rarely), metachronous (frequently) and
      sometimes with multicentric aspects. After the review of the epidemiological,
      pathogenetic, clinical, radiographic and histologic data, the authors present two
      cases of bilateral Warthin's tumor, metachronous (7 years), nodular-isolated in
      the first one and metachronous (5 years), nodular-multicentric in the second one.
      The patients after CAT scan and NMR examinations, and a fine needle aspiration
      biopsy were treated with superficial parotidectomy with preservation of the
      facial nerve. In our experience the management of patients affected by Warthin's
      tumors, needs the following steps: CAT scan and NMR examinations to outline
      multiple and bilateral lesions, fine needle aspiration biopsy, superficial
      parotidectomy with preservation of the facial nerve, an extended follow-up (10
      years after the last surgery).

PMID- 7739486
TI  - [The correlation between sonoarthrographic and arthroscopic data. Its
      verification in a clinical case].
AB  - Surgical arthroscopy is an important option in the treatment of TMJ pain and
      disfunction. Also sonography of the TMJ is a technique that with recent
      improvements graphically displays and analyzes joint sounds. A comparison was
      performed between presurgical data obtained by sonography, clinical findings
      obtained by surgical arthroscopy, and post surgical control performed by
      sonography. Precise correlation between these data was found in the case
      reported.

PMID- 7739488
TI  - [A case of rhino-orbital mucormycosis in a subject with compensated diabetes
      mellitus].
AB  - Mucormycosis is a fungal infection, the most frequent form begins in the nose and
      the paranasal sinuses and can rich the brain. It's a fulminant and often fatal
      disease, not well known to specialists. The authors present the case of the
      patient cured with medical (fluconazolo) and surgical therapy where resolved the
      disease.

PMID- 7739489
TI  - [Dilacerations: the clinical, diagnostic and therapeutic problems].
AB  - The authors consider the problems connected with diagnosis and prognosis of
      dilaceration. Case reports of varying prognosis importance are given as examples.

PMID- 7739490
TI  - [New research on endodontic carbon-fiber posts].
AB  - The authors present their clinical experience with fibre-carbon posts, which has
      been carried on for more than 4 years, supporting it with studies made in
      European and U.S.A. Universities, specially regarding the mechanical resistance
      and retention of those posts. Tests show luting procedures as the critical and
      improvable point. No real retention increase results using Sealbond and Flexi
      Flow composite cements; failure always occurs at cement-post junction. Using a
      special fibre-carbon post, named Composipost Retentive, which presents
      circumferential grooves, very superior retention is obtained. Using 5 types of
      composite cement (Sticky Post, Flexi-Flow, Sealbond, Super Bond and All Bond II),
      we reach a very high retention. Super Bond and All Bond II specially show a
      tensile strength over 120 kg measured with Instrom machine. Those two composite
      cements massively penetrate in dentinal tubules, giving best results in cement
      root channel interface.

PMID- 7739491
TI  - [A longitudinal analysis of dysfunctional pathology of the TMJ: an assessment of
      a sample of patients not undergoing therapy].
AB  - Concerning the different interpretation on the pathological and clinical
      evolution of the TMJ dysfunctions, the most common of these pathology is the
      condyle-disk incoordination. This study analyzed the evolution of TMJ
      dysfunctions examined at the maxillo-facial department of the University of Rome
      "La Sapienza". The non therapeutic approach does not consider an addition al
      control-sample of the non treated being itself a control-sample of a parallel
      work whose aim was to analyze patients who had undergone a complete therapeutic
      cycle.

PMID- 7739492
TI  - [Experimental considerations of the mechanism of lip and palate fusion].
AB  - Although harelip, cleft palate, or both, are by far the most common major facial
      malformations, the mechanisms underlying their embryogenesis are only now
      beginning to be understood; this is due to the complexity of primary and
      secondary palate development and the fact that appropriate methods for study have
      only recently been developed. The authors present a review of the most
      significant data regarding the etiology of hare lip and cleft palate, both in
      their physiopathogenic aspects and in their clinical morphology. The peculiarity
      of these malformations is outlined, supported by literature data and personal
      experimental experience.

PMID- 7739493
TI  - [Profile modifications induced by orthodontic forces studied by an analysis of
      the nasolabial angle].
AB  - The authors have studied the development modifications of the facial profile
      subsequent to the different types of headgear focusing attention on the nose
      labial angle variations. This study has evaluated separately the orthopedic
      action of the headgear measuring the variations of the columella inclination as
      regards the Frankfurt horizontal plane and the orthodontic action measuring the
      variation of the filter inclination as regards the Frankfurt horizontal plane.
      The study of the profile pictures of 20 patients in II Class I division treated
      with extra-oral traction and edgewise therapy showed that; while the high
      headgear determined a slight change of growth orientation in the nasal component
      of the nasal-jaw complex directing it upwards; the cervical headgear instead;
      determined a considerable descent of the nose with a consequent anti-aesthetic
      result.

PMID- 7739494
TI  - [The maxillofacial functional and esthetic surgical aspects in a case of
      osteopetrosis].
AB  - Osteopetrosis is an extremely rare condition characterized by an increase in
      osseous cell density. It shows three different hereditary patterns. Diagnosis is
      made by means of a 3D CT and an accurate study of hepatic and renal functions, as
      well as audiometric and labyrinth examination. In the frequent case of serious
      osseous alterations of the facial profile, surgical treatment is essential in
      order to obtain the best aesthetic and functional results.

PMID- 7739498
TI  - [A giant-cell tumor of the mandibular condyle. A report of a clinical case].
AB  - The authors present a case of a giant cell tumor of the mandibular condyle, which
      is a very rare condition. Problems relating to diagnosis and treatment are
      examined. Specifically non neoplastic and neoplastic lesions in which giant cells
      are identified have been evaluated.

PMID- 7739497
TI  - [The Gorlin-Goltz syndrome. A report of 2 cases].
AB  - Two cases of patients with Gorlin-Goltz syndrome are described. The Gorlin-Goltz
      syndrome is a polydistrectual, hereditary disease characterized by multiple
      keratocysts and basocellular nevomatosis. It is pointed out that the inconstancy
      of the main symptoms makes early diagnosis difficult. The histologic
      characteristics of odontogenic keratocysts and the possible etiopathogenetic
      relations between cystic lesions and hamartia of adjacent oral mucosa, as
      considered by Stoelinga, are also discussed. In view of the course of the cases
      presented, a surgical approach considering such potential findings, is supposed
      to favorably affect the clinical evolution in respect to a high relapsing drift.

PMID- 7739496
TI  - [Multiple heterogeneous cysts of the jaw. A clinical case].
AB  - A 23-year-old white man was referred to this Odontostomatologic Service for
      evaluation of palatal swelling lesion. Oral inspection showed a poor oral
      conditions and multiple caries. A panoramic radiograph revealed 3 mandibular and
      4 maxillary radiolucent lesions. No major nor minor clinical and radiographic
      criteria of Gorlin's syndrome were present; furthermore clinical features and
      laboratory blood values, ruled out a possible association with Maroteaux-Lamy,
      Hunter, and Hurler' syndromes and hyperparathyroidism. The 7 radiolucent lesions
      were surgically enucleated and the histologic study revealed that these lesions
      consisted in: 1 keratocyst, 1 naso-palatine cyst, 4 radicular cysts and 1 fiber
      connective tissue.

PMID- 7739499
TI  - The pathology of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic neurologic disease characterized in early
      phases by a cellular immune response and later by multiple areas of demyelination
      or plaques in the central nervous system (CNS) white matter. The clinical
      manifestations of the disease are highly variable, but probably are related to
      the extent of breakdown of the blood-brain barrier associated with inflammation
      in the acute phase, and with the extent of demyelination in the chronic phase.
      The initiating events of MS are not known, but current hypotheses include immune
      responses to an initiating viral infection and autoimmune responses to CNS myelin
      antigens. Both inflammatory and CNS resident cells contribute to the
      immunopathology of the disease. Chronic lesions are characterized by glial
      scarring and depletion of both oligodendrocytes and axons.

PMID- 7739501
TI  - Neuroimaging in multiple sclerosis.
AB  - Neuroimaging in multiple sclerosis is now dominated by MR imaging. This article
      will focus primarily on conventional MR imaging studies in multiple sclerosis,
      but will also discuss briefly some of the more recent advances related to MR
      imaging. Fast spin-echo imaging, fluid attenuated inversion recovery MR studies,
      three-dimensional volumetric studies, magnetization transfer, and magnetic
      resonance spectroscopy as it applies to multiple sclerosis are examined.

PMID- 7739500
TI  - The natural history of multiple sclerosis.
AB  - The natural history of MS is highly variable. There is substantial heterogeneity
      in the clinical manifestations but, at this point, it is reasonable to consider
      all idiopathic inflammatory demyelinating diseases of the central nervous system
      as representing a spectrum of the same disease. In large populations, 20% to 40%
      have "benign disease," defined as having less than moderate disability after 10
      years. Benign is a potentially misleading term because many of these patients
      subsequently will become disabled. Half will develop progressive MS within 10
      years and will require some form of walking aid within 15 years following the
      onset of MS. Survival is not greatly shortened in mildly disabled patients, but
      the observed mortality is increased four-fold over the general population in
      patients with advanced disability. Patients with the greatest risk of disability
      are those with PP MS and RR patients who are older at onset, have pyramidal or
      cerebellar involvement at onset, and who have frequent or prolonged attacks with
      incomplete recovery. The biological basis for the variation in the course of MS
      is understood only in a very limited way. The short- and long-term course of MS
      may be determined by different biological variables. Short-term benefit in
      clinical trials should not be assumed to indicate long-term reduction in the risk
      of permanent disability.

PMID- 7739495
TI  - [The Melkersson-Rosenthal syndrome. A report of 2 cases].
AB  - The Melkersson-Rosenthal syndrome is a rare condition of unknown
      etiopathogenesis. This syndrome is characterized by a triad of recurrent
      orofacial edema, recurrent facial palsy, and fissured tongue. In this paper two
      patients with Melkersson-Rosenthal syndrome are reported. Also the
      clinicopathologic aspects and diagnostic problems of this rare disease are
      discussed.

PMID- 7739502
TI  - Therapy for multiple sclerosis.
AB  - Multiple sclerosis is hypothesized to be a cell-mediated autoimmune disease
      directed against central nervous system myelin. Immunotherapy is directed at
      decreasing the autoimmune response using both specific and nonspecific modulation
      of the immune system in an attempt to halt accumulation of disability.
      Symptomatic therapy may also help multiple sclerosis patients.

PMID- 7739503
TI  - The psychosocial aspects of multiple sclerosis.
AB  - As we become more adept at measuring the neurologic deficits in MS, we are
      developing more effective measures of the broad psychosocial effects of the
      disease. These include emotional stresses, depression, cognitive changes, and
      decreasing activities in the family and community. In about half, cognitive
      changes will develop and, in some, the changes will occur early. Employment rates
      decline and the economic costs to the family and the health care system mount as
      the years go on. How well patients cope with the stresses on their personal
      lives, their relationships, and their families depends on many factors beyond the
      physical changes, such as their coping skills and their network of supportive
      people and resources. As we learn more about the changes occurring in the nervous
      system, we also are learning more about the psychological and social aspects of
      the disorder. Approaching the management of patients and their families with the
      broad view that recognizes both the neurologic and the psychosocial aspects of
      the disease results in more effective care for those with MS.

PMID- 7739504
TI  - Oligodendrocytes and myelin.
AB  - Although it was initially thought to be a passive structure, the oligodendrocyte
      and myelin unit is now considered highly dynamic with many important functions
      beyond its role in myelination. Inhibitors of neurite growth can be localized to
      oligodendrocyte and myelin, highlighting the importance of oligodendrocytes in
      general CNS maintenance and in neuronal regeneration following many types of CNS
      insults. Understanding of the genesis of oligodendrocytes and myelin is
      increasing and will surely lead to better strategies to treat demyelinating
      diseases including MS.

PMID- 7739505
TI  - The immunology of multiple sclerosis and its animal model, experimental allergic
      encephalomyelitis.
AB  - Two questions were posed at the beginning of this article. Is EAE a good model
      for MS? And, is MS an autoimmune disease? The first question is easier to address
      than the second. EAE is the best available model for the inflammatory processes
      that occur in MS, and for the disease process. The latter depends somewhat on
      study of chronic relapsing EAE, rather than early or mono-episodic EAE, which,
      although of great immunological interest, is of less relevance to the established
      disease that presents as MS. The second question asks whether MS fulfills Koch's
      postulates as an autoimmune disease. MS has all the hallmarks of an inflammatory
      disease of the CNS. The question then is whether the inflammation is autoimmune.
      The evidence presented shows a considerable autoimmune component to MS
      inflammation, raising the subsidiary question of whether autoimmune reactivity
      induces MS. This remains unanswerable for the present, and it should be kept in
      mind that the same question also would be unanswerable by observation of EAE. The
      major postulate therefore remains unfulfilled. Diagnosis of MS as an autoimmune
      disease requires definitive identification of the autoantigen; otherwise, the
      possibility remains open that this is a disease resulting from the inadvertent
      activation and dysregulation of immune processes in the CNS that, themselves, are
      not directed at that organ.

PMID- 7739506
TI  - Human retroviruses and demyelinating diseases.
AB  - The consequences of human retroviral infections have had an unprecedented impact
      on the medical, scientific, and social institutions of the last two decades of
      this century. The nervous system as an end target organ figures prominently in
      the constellation of diseases associated with HTLV and HIV infection and numerous
      syndrome complexes have been recognized that reflect dysfunction of the brain,
      spinal cord, nerve roots, peripheral nerves, or muscle. HAM/TSP, associated with
      HTLV-I and rarely with HTLV-II infections, and encephalomyelitis, associated with
      HIV infection, may present with clinical, laboratory, neuroelectrophysiologic,
      and neuroimaging features closely resembling MS. A careful systematic search for
      associated disease processes and review of the medical history, however should
      raise the suspicion of possible retroviral infection. In the appropriate setting,
      because of the pleiotropy in disease expression and the high prevalence of
      retroviral infection in many areas of the United States, clinicians should have a
      low threshold for ordering diagnostic testing for HIV and HTLV when considering a
      retroviral cause for a neurologic disorder. The retroviruses are pervasive
      throughout the vertebrate subphylum and share common elements within their genome
      that encode for promoters and structural proteins and are distinguished from each
      other by sets of transactivating and regulating genes. The latter group of genes
      serve to regulate viral replication by the induction and post-transcriptional and
      post-translational modification of retrovirally encoded gene products. In
      addition, the transactivating gene products can activate and upregulate the
      expression of a variety of host cellular genes, many of which possess immune
      related functions. The viral particle or specific components of certain viral
      structural proteins may be directly toxic to neural tissues. Also, during the
      replicative phase, retroviruses are recognized by host defense mechanisms, which
      mount considerable cellular and humoral immune responses. The spectrum of
      retroviral-associated neurologic diseases therefore may represent a complex
      interaction among viral antigen-induced immunity, the production of neurotoxic
      viral peptides, and the abnormal induction and expression of cellular genes with
      potent bioactivity.

PMID- 7739507
TI  - Genetics of multiple sclerosis.
AB  - The cause of MS is unknown. There is considerable circumstantial evidence that MS
      is a complex trait, probably autoimmune in nature, and is determined by both
      genetic and environmental factors. At present, it must be acknowledged, however,
      that our understanding of the pathogenesis of MS is minimal. Very little is known
      about the genes determining disease susceptibility and perhaps even less is
      understood about environmental factors that influence penetrance or the
      geographic distribution. This lack of knowledge results neither from lack of
      effort nor from a shortage of fertile imaginations. Almost every imaginable
      hypothesis has, in the past, found some support. The intractability of the
      problem could well result from its complexity, because answers to testable
      hypotheses are commonly negative or ambiguous. Today, the opportunity exists for
      researchers to provide such answers because of recent major developments. The
      first development is the recognition that MS research requires a relatively large
      pool of well-ascertained, carefully diagnosed, and longitudinally well
      characterized MS patients. The last two developments are the identification and
      successful application of statistical and molecular genetic techniques carrying
      sufficient power to allow the exploration of complex traits such as MS.

PMID- 7739508
TI  - Injury-control recommendations: bicycle helmets. National Center for Injury
      Prevention and Control, Centers for Disease Control and Prevention.
AB  - These recommendations on the use of bicycle helmets are the first in a series of
      Injury-Control Recommendations that are designed for state and local health
      departments or other organizations for use in planning injury control programs.
      Each publication in the series of Injury-Control Recommendations will provide
      information for program planners to use when implementing injury control
      interventions. These guidelines were developed for state and local agencies and
      organizations that are planning programs to prevent head injuries among
      bicyclists through the use of bicycle helmets. The guidelines contain information
      on the magnitude and extent of the problem of bicycle-related head injuries and
      the potential impact of increased helmet use; the characteristics of helmets,
      including biomechanical characteristics, helmet standards, and performance in
      actual crash conditions; barriers that impede increased helmet use; and
      approaches to increasing the use of bicycle helmets within the community. In
      addition, bicycle helmet legislation and community educational campaigns are
      evaluated.

PMID- 7739509
TI  - Compendium of animal rabies control, 1995 National Association of State Public
      Health Veterinarians, Inc.

PMID- 7739510
TI  - Assessment of the impact of a 100% smoke-free ordinance on restaurant sales--West
      Lake Hills, Texas, 1992-1994.
AB  - Exposure to environmental tobacco smoke (ETS), which is associated with adverse
      health effects among nonsmokers (1), is a health hazard of particular concern for
      patrons and employees in restaurants (2). To protect nonsmokers, many local
      governments have enacted ordinances requiring restaurants to be smoke-free.
      However, the potential economic impact of these laws on restaurants is an
      important concern for restaurant owners. On June 1, 1993, the city of West Lake
      Hills (a suburb of Austin), Texas (1995 population: 3000), implemented an
      ordinance requiring a 100% smoke-free environment in all commercial
      establishments to which the public has access, including all restaurants and
      restaurants with bar areas. This report summarizes an assessment of sales in
      restaurants during June 1993-December 1994 compared with January 1992-May 1993.

PMID- 7739511
TI  - Smoking-attributable mortality--Mexico, 1992.
AB  - Cigarette smoking causes neoplastic, respiratory, and cardiovascular diseases
      that contribute substantially to disability, death, and medical-care expenditures
      (1). In the United States, cigarette smoking is the leading preventable cause of
      premature death (1). Although the prevalence of cigarette smoking in Mexico (26%
      in 1993 [2]) is similar to that in the United States, smoking-attributable
      mortality has not been recently estimated for Mexico or most other developing
      countries that are experiencing increases in chronic diseases. To assist in the
      development of programs for preventing tobacco use, the Ministry of Health of
      Mexico used a modified version of the software program Smoking-Attributable
      Mortality, Morbidity, and Economic Costs (SAMMEC) to estimate smoking-related
      mortality (3). This report summarizes trends in the occurrence of smoking-related
      diseases in Mexico and estimates smoking-attributable mortality and years of
      potential life lost before age 65 years (YPLL-65) in 1992.

PMID- 7739512
TI  - Outbreak of Ebola viral hemorrhagic fever--Zaire, 1995.
AB  - On May 6, 1995, CDC was notified by health authorities and the U.S. Embassy in
      Zaire of an outbreak of viral hemorrhagic fever (VHF)-like illness in Kikwit,
      Zaire (1995 population: 400,000), a city located 240 miles east of Kinshasa. The
      World Health Organization and CDC were invited by the Government of Zaire to
      participate in an investigation of the outbreak. This report summarizes
      preliminary findings from this ongoing investigation.

PMID- 7739514
TI  - Surveillance of family planning services at Title X clinics and characteristics
      of women receiving these services, 1991.
AB  - PROBLEM/CONDITION: Public health surveillance data describing family planning
      services at Title X clinics and characteristics of women receiving these services
      during 1991 are contained in this report. These data update previously published
      information concerning characteristics of women and services at such clinics
      during 1981. REPORTING PERIOD COVERED: 1991. DESCRIPTION OF SYSTEM: Data
      characterizing patients and services were reported by family planning clinics to
      Title X grantees. These data for 1991 were provided by all 75 grantees to CDC's
      Family Planning Services Surveillance (FPSS) project. RESULTS: In 1991, 4.2
      million women received services at Title X clinics. Overall, 69.5% of family
      planning patients had chosen oral contraceptives as their method of
      contraception, and 64.7% of patients were at or below the federal poverty level.
      In addition to information characterizing patients and services at Title X
      clinics, this report also evaluated current data-collection methods used by Title
      X grantees. Complexities in the analysis reflected variations in the quality and
      availability of data, including differences in definitions, data-collection
      instruments at the clinic level, and data categories. INTERPRETATION: The number
      and characteristics of family planning patients receiving services at Title X
      clinics during 1991 were similar to the number and characteristics during 1981.
      Furthermore, these results underscore the need to improve the quality and
      timeliness of family planning data and to facilitate program planning and
      operations at the grantee level. ACTIONS TAKEN: These surveillance findings have
      been communicated to state family planning administrators and to national Title X
      program administrators. This information will be used to assess how publicly
      funded family planning clinics currently contribute to health-care delivery and
      how these clinics might contribute to a national system of reproductive health
      care services in the future.

PMID- 7739513
TI  - Youth risk behavior surveillance--United States, 1993.
AB  - PROBLEM/CONDITION: Priority health risk behaviors that contribute to the leading
      causes of mortality, morbidity, and social problems among youth and adults often
      are established during youth, extend into adulthood, and are interrelated.
      REPORTING PERIOD: February through May 1993. DESCRIPTION OF SYSTEM: The Youth
      Risk Behavior Surveillance System (YRBSS) monitors six categories of priority
      health risk behaviors among youth and young adults: behaviors that contribute to
      unintentional and intentional injuries, tobacco use, alcohol and other drug use,
      sexual behaviors, dietary behaviors, and physical activity. The YRBSS includes a
      national, school-based survey conducted by CDC and state and local school-based
      surveys conducted by state and local education agencies. This report summarizes
      results from the national survey, 24 state surveys, and nine local surveys
      conducted among high school students during February through May 1993. RESULTS
      AND INTERPRETATION: In the United States, 72% of all deaths among school-age
      youth and young adults are from four causes: motor vehicle crashes, other
      unintentional injuries, homicide, and suicide. Results from the 1993 YRBSS
      suggest that many high school students practice behaviors that may increase their
      likelihood of death from these four causes: 19.1% rarely or never used a safety
      belt, 35.3% had ridden with a driver who had been drinking alcohol during the 30
      days preceding the survey, 22.1% had carried a weapon during the 30 days
      preceding the survey, 80.9% ever drank alcohol, 32.8% ever used marijuana, and
      8.6% had attempted suicide during the 12 months preceding the survey. Substantial
      morbidity and social problems among adolescents also result from unintended
      pregnancies and sexually transmitted diseases, including human immunodeficiency
      virus (HIV) infection. YRBSS results indicate that in 1993, 53.0% of high school
      students had had sexual intercourse, 52.8% of sexually active students had used a
      condom during last sexual intercourse, and 1.4% ever injected an illegal drug.
      Among adults, 67% of all deaths are from three causes: heart disease, cancer, and
      stroke. In 1993, many high school students practiced behaviors that may increase
      the risk for these health problems: 30.5% of high school students had smoked
      cigarettes during the 30 days preceding the survey, only 15.4% had eaten five or
      more servings of fruits and vegetables during the day preceding the survey, and
      only 34.3% had attended physical education class daily. ACTIONS TAKEN: YRBSS data
      are being used nationwide by health and education officials to improve school
      health policies and programs designed to reduce risks associated with the leading
      causes of mortality and morbidity. At the national level, YRBSS data are being
      used to measure progress toward achieving 26 national health objectives and one
      of eight National Education Goals.

PMID- 7739515
TI  - Abortion surveillance--United States, 1991.
AB  - PROBLEM/CONDITION: From 1980 through 1991, the number of legal induced abortions
      reported to CDC remained stable, varying each year by < or = 5%. REPORTING PERIOD
      COVERED: This report summarizes and reviews information reported to CDC regarding
      legal induced abortions obtained in the United States during 1991. DESCRIPTION OF
      SYSTEM: For each year since 1969, CDC has compiled abortion data received from 52
      reporting areas: 50 states, the District of Columbia, and New York City. RESULTS:
      In 1991, 1,388,937 abortions were reported--a 2.8% decrease from 1990. The
      abortion ratio was 339 legal induced abortions per 1,000 live births, and the
      abortion rate was 24 per 1,000 women 15-44 years of age. Women who were
      undergoing an abortion were more likely to be young, white, and unmarried; most
      had had no previous live births and had been obtaining an abortion for the first
      time. More than half (52%) of all abortions were performed at or before the 8th
      week of gestation, and 88% were before the 13th week. Younger women (i.e., women
      < 19 years of age) were more likely to obtain abortions later in pregnancy than
      were older women. INTERPRETATION: Since 1980, the number and rate of abortions
      have remained relatively stable, with only small year-to-year fluctuations of <
      or = 5%. However, since 1987, the abortion-to-live-birth ratio has declined; in
      1991, the abortion ratio was the lowest recorded since 1977. An increasing rate
      of childbearing may partially account for this decline. ACTIONS TAKEN: An
      accurate assessment of the number and characteristics of women who obtain
      abortions in the United States is necessary both to monitor efforts to prevent
      unintended pregnancy and to identify and reduce preventable causes of morbidity
      and mortality associated with abortions.

PMID- 7739516
TI  - Multiple independent inputs are required for activation of the p70 S6 kinase.
AB  - Previous studies have shown that the noncatalytic carboxy-terminal tail of the
      p70 S6 kinase (amino acids 422 to 525) contains an autoinhibitory pseudosubstrate
      domain that is phosphorylated in situ during activation and in vitro by mitogen
      activated protein kinases. The present study shows that a recombinant p70 deleted
      of the carboxy-terminal tail (p70 delta CT104) nevertheless exhibits a basal and
      serum-stimulated 40S kinase activity and susceptibility to inhibition by
      wortmannin very similar to those of the parent, full-length p70 kinase. Carboxy
      terminal deletion reduces the extent of maximal inhibition produced by rapamycin,
      from > 95% in the full-length p70 to 60 to 80% in p70 delta CT104, without
      altering the sensitivity to rapamycin inhibition (50% inhibitory concentration of
      2 nM). Serum activation of p70 delta CT104, as with the parent, full-length p70,
      is accompanied by an increase in 32P content (about twofold) in situ and a
      slowing in electrophoretic mobility; both modifications are inhibited by
      pretreatment with wortmannin or rapamycin. 32P-peptide maps of p70 delta CT104
      show multisite phosphorylation, and wortmannin and rapamycin appear to cause
      preferential dephosphorylation of the same subset of sites. Thus, it is likely
      that activation of the kinase requires phosphorylation of p70 at sites in
      addition to those previously identified in the carboxy-terminal tail. Evidence
      that the carboxy-terminal tail actually functions as a potent intramolecular
      inhibitor of kinase activity in situ is uncovered by deletion of a short acidic
      segment (amino acids 29 to 46) from the p70 amino-terminal noncatalytic region.
      Deletion of amino acids 29 to 46 causes a >95% inhibition of p70 activity despite
      continue phosphorylation of the carboxy-terminal tail in situ; additional
      deletion of the carboxy-terminal tail (yielding p70 delta 29-46/ delta CT104)
      increases activity 10-fold, to a level approaching that of p70 delta CT104.
      Deletion of residues 29 to 46 also abolishes completely the sensitivity of p70 to
      inhibition by rapamycin but does not alter the susceptibility to activation by
      serum of inhibition by wortmannin. Although the mechanisms underlying the effects
      of the delta 29-46 deletion are not known, they are not attributable to loss of
      the major in situ p70 phosphorylation site at Ser-40. Thus, activation of the p70
      S6 kinase involves multiple, independent inputs directed at different domains of
      the p70 polypeptide. Disinhibition from the carboxy-terminal tail requires, in
      addition to its multisite phosphorylation, an activating input dependent on the
      presence of amino acids 29 to 46; this p70-activating input may be the same as
      that inhibited by rapamycin but is distinct from that arising from the wortmannin
      inhibitable phosphatidylinositol 3-kinase. In addition, as exemplified by the
      rapamycin-resistant but mitogen- and wortmannin-sensitive p70 delta 29-46/ delta
      CT104 mutant, a further activating input, which probably involves site-specific
      phosphorylation in the segment between amino acids 46 to 421, is necessary.

PMID- 7739517
TI  - Functional regulation of thyroid hormone receptor variant TR alpha 2 by
      phosphorylation.
AB  - The thyroid hormone (T3) receptor (TR) variant TR alpha 2 is abundant in brain
      but does not bind T3 because of its unique C terminus. The only known function of
      TR alpha 2, inhibition of TR-dependent transactivation, involves competition for
      T3 response elements. Paradoxically, in vitro-translated TR alpha 2 bound poorly
      to these sites. We report here that dephosphorylation of TR alpha 2 restored its
      DNA binding. Mutation of C-terminal serine residues to alanine (TR alpha 2-SA)
      was equally effective. The C terminus of TR alpha 2 was phosphorylated in a human
      cell line, whereas that of TR alpha 2-SA was not. Conversely, TR alpha 2-SA was a
      much better inhibitor of T3 action than was wild-type TR alpha 2. The dominant
      negative activity of TR alpha 2-SA was less than stoichiometric with TR
      concentration, possibly because it was unable to heterodimerize with retinoid X
      receptor, which enhances the binding of other TRs. Purified casein kinase II as
      well as a reticulocyte casein kinase II-like activity phosphorylated TR alpha 2
      on serines 474 and 475. Mutation of these two residues to alanine was sufficient
      to restore DNA binding. Thus, DNA binding by TR alpha 2 is regulated by
      phosphorylation at a site distant from the DNA-binding domain. The increased
      dominant negative activity of a nonphosphorylatable form of TR alpha 2 suggests
      that phosphorylation may provide a rapid, T3-independent mechanism for cell
      specific modulation of the expression of T3-responsive genes.

PMID- 7739518
TI  - Developmental abnormalities in mice transgenic for bovine oncostatin M.
AB  - Oncostatin M belongs to the subfamily of hematopoietin cytokines that binds a
      receptor complex containing gp130. To date, only the human form of oncostatin M
      has been identified, and its evolutionary conservation is unresolved. We have
      isolated a bovine gene whose open reading frame encodes a precursor protein that
      is 58% identical to human oncostatin M. A comparison of the bovine and human
      amino acid sequences predicts significant similarity, including the four-alpha
      helical-bundle structure and the placement of disulfide bridges. As with the
      human protein, bovine oncostatin M binds specific receptors on human H2981 cells
      and inhibits the proliferation of human A375 tumor cells and mouse M1 leukemia
      cells. To identify activities regulated in vivo, we injected bovine oncostatin M
      fusion genes containing various tissue-specific promoters into mouse embryos. The
      frequencies of transgenic mice were reduced significantly, suggesting that
      overexpression of the bovine cytokine is detrimental to normal mouse development.
      In addition to deaths associated with expression in neurons and keratinized
      epithelia, bovine oncostatin M caused abnormalities in bone growth and
      spermatogenesis, stimulated fibrosis surrounding islets in the pancreas, and
      disrupted normal lymphoid tissue development. This work establishes the existence
      of a nonprimate oncostatin M gene and provides the first demonstration that this
      cytokine can function in a pleiotropic manner in vivo. Information regarding
      bovine oncostatin M may help characterize the structure and function of this
      cytokine in other vertebrate species.

PMID- 7739519
TI  - Tumor necrosis factor alpha-induced apoptosis in human neuronal cells: protection
      by the antioxidant N-acetylcysteine and the genes bcl-2 and crmA.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a candidate human immunodeficiency
      virus type 1-induced neurotoxin that contributes to the pathogenesis of AIDS
      dementia complex. We report here on the effects of exogenous TNF-alpha on SK-N-MC
      human neuroblastoma cells differentiated to a neuronal phenotype with retinoic
      acid, TNF-alpha caused a dose-dependent loss of viability and a corresponding
      increase in apoptosis in differentiated SK-N-MC cells but not in undifferentiated
      cultures. Importantly, intracellular signalling via TNF receptors, as measured by
      activation of the transcription factor NF-kappa B, was unaltered by retinoic acid
      treatment. Finally, overexpression of bcl-2 or crmA conferred resistance to
      apoptosis mediated by TNF-alpha, as did the addition of the antioxidant N
      acetylcysteine. These results suggest that TNF-alpha induces apoptosis in
      neuronal cells by a pathway that involves formation of reactive oxygen
      intermediates and which can be blocked by specific genetic interventions.

PMID- 7739520
TI  - The genomic organization of the region containing the Drosophila melanogaster
      rpL7a (Surf-3) gene differs from those of the mammalian and avian Surfeit loci.
AB  - The Surf-3 gene of the unusually tight mouse Surfeit locus gene cluster has been
      identified as the highly conserved ribosomal protein gene L7a (rpL7a). The
      topography and juxtaposition of the Surfeit locus genes are conserved for the 600
      million years of divergent evolution between mammals and birds. This suggests cis
      interaction and/or coregulation of the genes and suggests that, within this
      locus, gene organization plays an important role in gene expression. The further
      evolutionary conservation of the organization of the Surfeit locus was
      investigated. A cDNA encoding the Drosophila melanogaster homolog of the Surf
      3/rpL7a gene was cloned, was shown to be present as a single copy, and was
      expressed constitutively at high levels throughout development. Genomic cosmid
      clones encompassing the gene and its surrounding DNA were isolated. The gene was
      determined to have five introns, of which two were located in the 5' untranslated
      region of the gene. The remaining three introns had splice sites at positions
      equivalent to those found in the Surf-3/rpL7a mammalian homologs. S1 analysis and
      5' rapid amplification of cDNA ends both confirmed the start of transcription to
      occur in a polypyrimidine tract in the absence of a TATA box in the promoter. The
      genomic region around the Surf-3/rpL7a gene was analyzed by low-stringency
      hybridization with murine Surfeit gene probes, by partial sequence analysis, and
      by hybridization of fragments to Northern (RNA) blots. No homologs of other
      members of the Surfeit gene cluster were detected in close proximity to the D.
      melanogaster Surf-3/rpL7a gene. However, a gene which was detected directly 3' to
      the Surf-3/rpL7a gene was shown to encode a homolog of a mammalian serine
      pyruvate aminotransferase.

PMID- 7739521
TI  - Src activity increases and Yes activity decreases during mitosis of human colon
      carcinoma cells.
AB  - Src and Yes protein-tyrosine kinase activities are elevated in malignant and
      premalignant tumors of the colon. To determine whether Src activity is elevated
      throughout the human colon carcinoma cell cycle as it is in polyomavirus middle T
      antigen- or F527 Src-transformed cells, and whether Yes activity, which is lower
      than that of Src in the carcinoma cells, is regulated differently, we measured
      their activities in cycling cells. We observed that the activities of both
      kinases were higher throughout all phases of the HT-29 colon carcinoma cell cycle
      than in corresponding phases of the fibroblast cycle. In addition, during mitosis
      of HT-29 cells, Src specific activity increased two- to threefold more, while Yes
      activity and abundance decreased threefold. The decreased steady-state protein
      levels of Yes during mitosis appeared to be due to both decreased synthesis and
      increased degradation of the protein. Inhibition of tyrosine but not
      serine/threonine phosphatases abolished the mitotic activation of Src. Mitotic
      Src was phosphorylated at novel serine and threonine sites and dephosphorylated
      at Tyr-527. Two cellular proteins (p160 and p180) were phosphorylated on tyrosine
      only during mitosis. Tyrosine phosphorylation of several other proteins decreased
      during mitosis. Thus, Src in HT-29 colon carcinoma cells, similar to Src
      complexed to polyomavirus middle T antigen or activated by mutation at Tyr-527,
      is highly active in all phases of the cell cycle. Moreover, Src activity further
      increases during mitosis, whereas Yes activity and abundance decrease. Thus, Src
      and Yes appear to be regulated differently during mitosis of HT-29 colon
      carcinoma cells.

PMID- 7739522
TI  - Dual functions of the AML1/Evi-1 chimeric protein in the mechanism of
      leukemogenesis in t(3;21) leukemias.
AB  - The chromosomal translocation t(3;21)(q26;q22), which is found in blastic crisis
      in chronic myelogenous leukemias and myelodysplastic syndrome-derived leukemias,
      produces AML1/Evi-1 chimeric transcription factor and is thought to play
      important roles in acute leukemic transformation of hemopoietic stem cells. We
      report here the functional analyses of AML1/Evi-1. It was revealed that AML1/Evi
      1 itself does not alter the transactivation level through mouse polyomavirus
      enhancer-binding protein 2 (PEBP2; PEA2) sites (binding site of AML1) but
      dominantly suppresses the transactivation by intact AML1, which is assumed to be
      a stimulator of myeloid cell differentiation. DNA-binding competition is a
      putative mechanism of such dominant negative effects of AML1/Evi-1 because it
      binds to PEBP2 sites with higher affinity than AML1 does. Furthermore, AML1/Evi-1
      stimulated c-fos promoter transactivation and increased AP-1 activity, as Evi-1
      (which is not normally expressed in hemopoietic cells) did. Experiments using
      deletion mutants of AML1/Evi-1 showed that these two functions are mutually
      independent because the dominant negative effects on intact AML1 and the
      stimulation of AP-1 activity are dependent on the runt domain (DNA-binding domain
      of AML1) and the zinc finger domain near the C terminus, respectively.
      Furthermore, we showed that AML1/Evi-1 blocks granulocytic differentiation,
      otherwise induced by granulocyte colony-stimulating factor, of 32Dcl3 myeloid
      cells. It was also suggested that both AML1-derived and Evi-1-derived portions of
      the fusion protein play crucial roles in this differentiation block. We conclude
      that the leukemic cell transformation in t(3;21) leukemias is probably caused by
      these dual functions of AML1/Evi-1 chimeric protein.

PMID- 7739523
TI  - The unique amino-terminal domain of p56lck regulates interactions with tyrosine
      protein phosphatases in T lymphocytes.
AB  - The catalytic activity of p56lck is repressed by phosphorylation of a conserved
      carboxy-terminal tyrosine residue (tyrosine 505). Accumulating data show that
      this phosphorylation is mediated by the tyrosine protein kinase p50csk and that
      it is reversed by the transmembrane tyrosine protein phosphatase CD45. Recent
      studies have indicated that dephosphorylation of tyrosine 505 in resting T cells
      is necessary for the initiation of antigen-induced T-cell activation. To better
      understand this phenomenon, we have characterized the factors regulating tyrosine
      505 phosphorylation in an antigen-specific T-cell line (BI-141). As is the case
      for other T-cell lines, Lck molecules from unstimulated BI-141 cells exhibited a
      pronounced dephosphorylation of the inhibitory carboxyl-terminal tyrosine. This
      state could be corrected by incubation of cells with the tyrosine protein
      phosphatase inhibitor pervanadate, suggesting that it reflected the unrestricted
      action of tyrosine protein phosphatases. In structure-function analyses, mutation
      of the site of Lck myristylation (glycine 2) partially restored phosphorylation
      at tyrosine 505 in BI-141 cells. Since the myristylation-defective mutant also
      failed to stably associate with cellular membranes, this effect was most probably
      the consequence of removal of p56lck from the vicinity of membrane phosphatases
      like CD45. Deletion of the unique domain of Lck, or its replacement by the
      equivalent sequence from p59fyn, also increased the extent of tyrosine 505
      phosphorylation in vivo. This effect was unrelated to changes in Lck membrane
      association and therefore was potentially related to defects in crucial protein
      protein interactions at the membrane. In contrast, deletion of the SH3 or SH2
      domain, or mutation of the phosphotransfer motif (lysine 273) or the site of
      autophosphorylation (tyrosine 394), had no impact on phosphate occupancy at
      tyrosine 505. In combination, these results indicated that the
      hypophosphorylation of the inhibitory tyrosine of p56(lck) in T lymphocytes is
      likely the result of the predominant action of tyrosine protein phosphatases.
      Moreover, they showed that both the amino-terminal myristylation signal and the
      unique domain of p56(lck) play critical roles in this process.

PMID- 7739524
TI  - Sequential mutations in the interleukin-3 (IL3)/granulocyte-macrophage colony
      stimulating factor/IL5 receptor beta-subunit genes are necessary for the complete
      conversion to growth autonomy mediated by a truncated beta C subunit.
AB  - An amino-terminally truncated beta C receptor (beta C-R) subunit of the
      interleukin-3 (IL3)/granulocyte-macrophage colony-stimulating factor/IL5 receptor
      complex mediates factor-independent and tumorigenic growth in two spontaneous
      mutants of a promyelocytic cell line. The constitutive activation of the JAK2
      protein kinase in these mutants confirms that signaling occurs through the
      truncated receptor protein. Noteworthily, in addition to a 10-kb deletion in the
      beta C-R subunit gene encoding the truncated receptor, several secondary and
      independent mutations that result in the deletion or functional inactivation of
      the allelic beta C-R subunit and the closely related beta IL3-R subunit genes
      were observed in both mutants, suggesting that such mutations are necessary for
      the full oncogenic penetrance of the truncated beta C-R subunit. Reversion of
      these mutations by the expression of the wild-type beta C-R in the two mutants
      resulted in a fivefold decrease in cloning efficiency of the mutants in the
      absence of IL3, confirming a functional interaction between the wild-type and
      truncated proteins. Furthermore, expression of the truncated beta C-R subunit in
      factor-dependent myeloid cells did not immediately render the cells autonomous
      but increased the spontaneous frequency to factor-independent growth by 4 orders
      of magnitude. Implications for both leukemogenic progression and receptor-subunit
      interaction and signaling are discussed.

PMID- 7739525
TI  - Inducible degradation of I kappa B alpha in vitro and in vivo requires the acidic
      C-terminal domain of the protein.
AB  - After exposure of cells to tumor necrosis factor (TNF), I kappa B alpha is
      rapidly degraded by a proteolytic activity that is required for nuclear
      localization and activation of transcription factor NF-kappa B. To investigate
      this problem, we have developed a cell-free system to study the degradation of I
      kappa B alpha initiated in vivo. In this in vitro system, characteristics of
      endogenous I kappa B alpha degradation were comparable to those observed in vivo.
      Recombinant I kappa B alpha, when added to lysates from cells exposed to TNF, was
      specifically degraded by a cellular proteolytic activity; however, it was stable
      in extracts from unstimulated cells. Inhibition characteristics of the
      proteolytic activity responsible for I kappa B alpha degradation suggest the
      involvement of a serine protease. Analysis of mutated forms of I kappa B alpha in
      the in vitro system demonstrated that an I kappa B alpha species which was unable
      to interact with NF-kappa B was still efficiently degraded. In contrast, deletion
      of the C-terminal 61 amino acids from I kappa B alpha rendered the protein
      resistant to proteolytic degradation. Expression of I kappa B alpha mutated forms
      in COS-7 cells confirmed the importance of the C-terminal domain for the
      degradation of the protein in vivo following cell activation. Thus, it is likely
      that the acidic, negatively charged region represented by the C-terminal 61 amino
      acids of the protein contains residues critical for TNF-inducible degradation of
      I kappa B alpha.

PMID- 7739526
TI  - A polymerase switch in the synthesis of rRNA in Saccharomyces cerevisiae.
AB  - Transcription of ribosomal DNA by RNA polymerase I is believed to be the sole
      source of the 25S, 18S, and 5.8S rRNAs in wild-type cells of Saccharomyces
      cerevisiae. Here we present evidence for a switch from RNA polymerase I to RNA
      polymerase II in the synthesis of a substantial fraction of those rRNAs in
      respiratory-deficient (petite) cells. The templates for the RNA polymerase II
      transcripts are largely, if not exclusively, episomal copies of ribosomal DNA
      arising from homologous recombination events within the ribosomal DNA repeat on
      chromosome XII. Ribosomal DNA contains a cryptic RNA polymerase II promoter that
      is activated in petites; it overlaps the RNA polymerase I promoter and produces a
      transcript equivalent to the 35S precursor rRNA made by RNA polymerase I. Yeast
      cells that lack RNA polymerase I activity, because of a disruption of the RPA135
      gene that encodes subunit II of the enzyme, can survive by using the RNA
      polymerase II promoter in ribosomal DNA to direct the synthesis of the 35S rRNA
      precursor. This polymerase switch could provide cells with a mechanism to
      synthesize rRNA independent of the controls of RNA polymerase I transcription.

PMID- 7739527
TI  - Negative regulation of the vascular smooth muscle alpha-actin gene in fibroblasts
      and myoblasts: disruption of enhancer function by sequence-specific single
      stranded-DNA-binding proteins.
AB  - Transcriptional activation and repression of the vascular smooth muscle (VSM)
      alpha-actin gene in myoblasts and fibroblasts is mediated, in part, by positive
      and negative elements contained within an approximately 30-bp polypurine
      polypyrimidine tract. This region contains binding sites for an essential
      transcription-activating protein, identified as transcriptional enhancer factor I
      (TEF-1), and two tissue-restrictive, sequence-specific, single-stranded-DNA
      binding activities termed VACssBF1 and VACssBF2. TEF-1 has no detectable single
      stranded-DNA-binding activity, while VACssBF1 and VACssBF2 have little, if any,
      affinity for double-stranded DNA. Site-specific mutagenesis experiments
      demonstrate that the determinants of VACssBF1 and VACssBF2 binding lie on
      opposite strands of the DNA helix and include the TEF-1 recognition sequence.
      Functional analysis of this region reveals that the CCAAT box-binding protein
      nuclear factor Y (NF-Y) can substitute for TEF-1 in activating VSM alpha-actin
      transcription but that the TEF-1-binding site is essential for the maintenance of
      full transcriptional repression. Importantly, replacement of the TEF-1-binding
      site with that for NF-Y diminishes the ability of VACssBF1 and VACssBF2 to bind
      to separated single strands. Additional activating mutations have been identified
      which lie outside of the TEF-1-binding site but which also impair single-stranded
      DNA-binding activity. These data support a model in which VACssBF1 and VACssBF2
      function as repressors of VSM alpha-actin transcription by stabilizing a local
      single-stranded-DNA conformation, thus precluding double-stranded-DNA binding by
      the essential transcriptional activator TEF-1.

PMID- 7739528
TI  - Functional synergy and physical interactions of the erythroid transcription
      factor GATA-1 with the Kruppel family proteins Sp1 and EKLF.
AB  - An unresolved aspect of current understanding of erythroid cell-specific gene
      expression relates to how a limited number of transcriptional factors cooperate
      to direct high-level expression mediated by cis-regulatory elements separated
      over large distances within globin loci. In this report, we provide evidence that
      GATA-1, the major erythroid transcription factor, activates transcription in a
      synergistic fashion with two Kruppel family factors, the ubiquitous protein Sp1
      and the erythroid-restricted factor EKLF (erythroid Kruppel-like factor), which
      recognize GC and/or GT/CACC motifs. Binding sites for both GATA-1 and these
      Kruppel proteins (especially Sp1) are found in close association in the promoters
      and enhancers of numerous erythroid cell-expressed genes and appear to cooperate
      in directing their expression. We have shown that GATA-1 interacts physically
      with Sp1 and EKLF and that interactions are mediated through their respective DNA
      binding domains. Moreover, we show that GATA-1 and Sp1 synergize from a distance
      in constructs designed to mimic the architecture of globin locus control regions
      and downstream globin promoters. Finally, the formation of GATA-1-SP1 complexes
      was demonstrated in vivo by the ability of Sp1 to recruit GATA-1 to a promoter in
      the absence of GATA-binding sites. These experiments provide the first evidence
      for functionally important protein-protein interactions involved in erythroid
      cell-specific expression and suggest a mechanism by which DNA loops between locus
      control regions and globin promoters (or enhancers) might be formed or
      stabilized.

PMID- 7739529
TI  - Self-association of the erythroid transcription factor GATA-1 mediated by its
      zinc finger domains.
AB  - GATA-1, the founding member of a distinctive family of transcription factors, is
      expressed predominantly in erythroid cells and participates in the expression of
      numerous erythroid cell-expressed genes. GATA-binding sites are found in the
      promoters and enhancers of globin and nonglobin erythroid genes as well as in the
      alpha- and beta-globin locus control regions. To elucidate how GATA-1 may
      function in a variety of regulatory contexts, we have examined its protein
      protein interactions. Here we show that GATA-1 self-associates in solution and in
      whole-cell extracts and that the zinc finger region of the molecule is sufficient
      to mediate this interaction. This physical interaction can influence
      transcription, as GATA-1 self-association is able to recruit a transcriptionally
      active but DNA-binding-defective derivative of GATA-1 to promoter-bound GATA-1
      and result in superactivation. Through in vitro studies with bacterially
      expressed glutathione S-transferase fusion proteins, we have localized the
      minimal domain required for GATA-1 self-association to 40 amino acid residues
      within the C-terminal zinc finger region. Finally, we have detected physical
      interaction of GATA-1 with other GATA family members (GATA-2 and GATA-3) also
      mediated through the zinc finger domain. These findings have broad implications
      for the involvement of GATA factors in transcriptional control. In particular,
      the interaction of GATA-1 with itself and with other transcription factors may
      facilitate its function at diverse promoters in erythroid cells and also serve to
      bring together, or stabilize, loops between distant regulatory elements, such as
      the globin locus control regions and downstream globin promoters. We suggest that
      the zinc finger region of GATA-1, and related proteins, is multifunctional and
      mediates not only DNA binding but also important protein-protein interactions.

PMID- 7739530
TI  - Erythroid cell-specific mRNA stability elements in the alpha 2-globin 3'
      nontranslated region.
AB  - Very little is known about the mechanisms mediating longevities of mRNAs. As a
      means of identifying potential cis- and trans-acting elements which stabilize an
      individual mRNA, naturally occurring mutations that decreased stability of the
      normally long-lived globin mRNA were analyzed. Our previous studies demonstrated
      that a subset of mutations which allowed the translating ribosome to read through
      into the alpha 2-globin 3' nontranslated region (NTR) targeted the mutant mRNAs
      for accelerated turnover in erythroid cells but not in several nonerythroid cell
      lines (I. M. Weiss and S. A. Liebhaber, Mol. Cell. Biol. 14:8123-8132, 1994).
      These results suggested that translational readthrough interfered with some
      feature of the alpha 2-globin 3' NTR required for message stability in erythroid
      cells. To define the cis-acting sequences which comprise this erythroid cell
      specific stability determinant, scanning mutagenesis was performed on the alpha 2
      globin 3' NTR, and the stability of each mutant mRNA was examined during
      transient expression. Three cytidine-rich regions which are required for
      longevity of the alpha 2-globin mRNA were identified. However, in contrast to the
      readthrough mutations, base substitutions in these elements destabilize the
      message through a translation-independent mechanism. To account for these
      results, we propose that the cis-acting elements form a complex or determinant in
      the normal alpha 2-globin mRNA which protects the message from degradation in
      erythroid cells. Disruption of this determinant, by translational readthrough or
      because mutations in an element prevent or inhibit its formation, targets the
      message for accelerated turnover in these cells.

PMID- 7739531
TI  - A complex unidirectional signal element mediates GCN4 mRNA 3' end formation in
      Saccharomyces cerevisiae.
AB  - The yeast GCN4 3' element represents a class of polyadenylation sites which
      function unidirectionally and efficiently in test systems in vivo as well as in
      vitro. A complex signal element is required for polyadenylation activity with a
      minimal size of 116 nucleotides for the functional element. We subdivided this
      element into five regions (EL1 to EL5) of 16 to 26 nucleotides each. Each region
      was characterized by deletion analysis in an in vivo test system. Two TTTTTAT
      motifs are located in different regions (EL1 and EL4) upstream of the poly(A)
      site. The 3' end processing activity was significantly reduced when both motifs
      were mutated by site-directed mutagenesis and abolished when EL1 and EL4 were
      deleted. The major poly(A) site is located in EL5, 3 nucleotides downstream of
      the second TTTTTAT motif. Additional minor poly(A) sites are used in less than
      10% of the mRNA 3' ends. Deletion of EL3 resulted in a changed pattern of mRNA 3'
      ends by increased usage of the minor poly(A) addition sites. The major poly(A)
      site in EL5 can be removed without loss of function when sequences upstream of
      EL1 are present. The tripartite TAG...TATGT...TTT sequence located downstream of
      EL5 is not required for function.

PMID- 7739532
TI  - Retinoic acid receptor alpha suppresses transformation by v-myb.
AB  - Retinoic acid (RA) is capable of inducing the differentiation of various
      myelomonocytic cell lines. During this differentiation process, the levels of c
      myb expression decline, suggesting that the RA receptor (RAR) may act in part by
      down-regulating this proto-oncogene. We have now investigated whether the RAR can
      also inhibit the function of Myb proteins themselves. We have found that
      transcriptional activation of a Myb-responsive reporter gene can be inhibited by
      RA in a human monocytic cell line. This inhibition could not be overcome by the
      expression of exogenous Myb. The RAR did not interfere with DNA binding by Myb
      proteins in vitro, suggesting that the functional inhibition occurs at the level
      of transcriptional activation. To determine the biological relevance of the
      inhibition of Myb proteins by the RAR, we have used v-myb-transformed monoblasts.
      These cells differentiate into macrophages in the presence of phorbol ester
      (tetradecanoyl phorbol acetate [TPA]) but are normally unresponsive to RA
      treatment. The introduction of an inducible, exogenous RAR alpha into v-myb
      transformed monoblasts permitted an RA-dependent differentiation into macrophage
      like cells similar to those induced by TPA. These results demonstrate that
      transformation by v-myb is recessive to RAR alpha and imply that many types of
      non-RA-responsive leukemia cells may become responsive following the introduction
      of the RAR.

PMID- 7739533
TI  - Mapping of replication initiation sites in human ribosomal DNA by nascent-strand
      abundance analysis.
AB  - New techniques for mapping mammalian DNA replication origins are needed. We have
      modified the existing nascent-strand size analysis technique (L. Vassilev and
      E.M. Johnson, Nucleic Acids Res. 17:7693-7705, 1989) to provide an independent
      means of studying replication initiation sites. We call the new method nascent
      strand abundance analysis. We confirmed the validity of this method with
      replicating simian virus 40 DNA as a model. We then applied nascent-strand
      abundance and nascent-strand size analyses to mapping of initiation sites in
      human (HeLa) ribosomal DNA (rDNA), a region previously examined exclusively by
      two-dimensional gel electrophoresis methods (R.D. Little, T.H.K. Platt, and C.L.
      Schildkraut, Mol. Cell. Biol. 13:6600-6613, 1993). Our results partly confirm
      those obtained by two-dimensional gel electrophoresis techniques. Both studies
      suggest that replication initiates at relatively high frequency a few kilobase
      pairs upstream of the transcribed region and that many additional low-frequency
      initiation sites are distributed through most of the remainder of the ribosomal
      DNA repeat unit.

PMID- 7739535
TI  - Determinants of target gene specificity for ROR alpha 1: monomeric DNA binding by
      an orphan nuclear receptor.
AB  - The ROR alpha isoforms are orphan members of the steroid/thyroid/retinoid
      receptor superfamily. Previous DNA-binding studies indicated that ROR alpha
      isoforms bind to response elements consisting of a single copy of the core
      recognition sequence AGGTCA preceded by a 6-bp A/T-rich sequence and that the
      distinct amino-terminal domains of each isoform influence DNA-binding
      specificity. In this report, we have investigated in detail the protein
      determinants of target gene specificity for the ROR alpha 1 isoform and have now
      identified the minimal sequence both in its amino- and carboxy-terminal domains
      required for high-affinity DNA binding. High-resolution methylation and
      ethylation interference analyses and mixing of truncated proteins in a DNA
      binding assay show that ROR alpha 1 presumably binds along one face of the DNA
      helix as a monomer. By analogy to previous studies of the orphan receptors NGFI-B
      and FTZ-F1, extensive mutational analysis of the ROR alpha 1 protein shows that a
      domain extending from the carboxy-terminal end of the second conserved zinc
      binding motif is required for specific DNA recognition. However, point mutations
      and domain swap experiments between ROR alpha 1 and NGFI-B demonstrated that
      sequence-specific recognition dictated by the carboxy-terminal extension is
      determined by distinct subdomains in the two receptors. These results demonstrate
      that monomeric nuclear receptors utilize diverse mechanisms to achieve high
      affinity and specific DNA binding and that ROR alpha 1 represents the prototype
      for a distinct subfamily of monomeric orphan nuclear receptors.

PMID- 7739534
TI  - FAR1 and the G1 phase specificity of cell cycle arrest by mating factor in
      Saccharomyces cerevisiae.
AB  - Significant accumulation of Far1p is restricted to the G1 phase of the
      Saccharomyces cerevisiae cell cycle. Here we demonstrate yeast cell cycle
      regulation of Far1p proteolysis. Deletions within the 50 N-terminal amino acids
      of Far1p increase stability and reduce cell cycle regulation of Far1p abundance.
      Whereas wild-type Far1p specifically and exclusively promotes G1 phase arrest in
      response to mating factor, stabilized Far1p promoted arrest both during and after
      G1. The loss of the G1 specificity of Far1p action requires elimination of FAR1
      transcriptional regulation (by means of the GAL1 promoter) as well as N-terminal
      truncation. Thus, the cell cycle specificity of mating factor arrest may be
      largely due to cell cycle regulation of FAR1 transcription and protein stability.

PMID- 7739537
TI  - In vivo association of E2F and DP family proteins.
AB  - The mammalian transcription factor E2F plays an important role in regulating the
      expression of genes that are required for passage through the cell cycle. This
      transcriptional activity is inhibited by association with the retinoblastoma
      tumor suppressor protein (pRB) or its relatives p107 and p103. The first cDNA
      from the E2F family to be cloned was designated E2F-1, and multiple E2F family
      members have now been identified. They bind to DNA as heterodimers, interacting
      with proteins known as DP. Here we demonstrate that DP is also a family of
      polypeptides with at least two members (hDP-1 and hDP-2). Both hDP-1 and hDP-2
      bind to all E2F family members in vivo, and each complex is capable of activating
      transcription. However, the various E2F/DP complexes display strong differences
      in the ability to bind to either pRB or p107 in vivo, and the specificity of pRB
      or p107 binding is mediated by the E2F subunit.

PMID- 7739536
TI  - An E-box-mediated increase in cad transcription at the G1/S-phase boundary is
      suppressed by inhibitory c-Myc mutants.
AB  - To better understand the signaling pathways which lead to DNA synthesis in
      mammalian cells, we have studied the transcriptional activation of genes needed
      during the S phase of the cell cycle. Transcription of the gene encoding a
      pyrimidine biosynthetic enzyme, carbamoyl-phosphate synthase (glutamine
      hydrolyzing)/aspartate carbamoyltransferase/dihydroorotase (cad), increases at
      the G1/S-phase boundary. We have mapped the growth-dependent response element in
      the hamster cad gene to the extended palindromic E-box sequence, CCACGTGG, which
      is centered at +65 in the 5' untranslated sequence. Mutation of the E box
      abolished growth-dependent transcription, and an oligonucleotide corresponding to
      the cad sequence at +55 to +75 (+55/+75) restored growth-dependent regulation to
      nonresponsive cad promoter mutants when placed down-stream of the transcription
      start site. The same oligonucleotide conferred less G1/S-phase induction when
      placed upstream of basal promoter elements. An analogous oligonucleotide
      containing the mutant E box had no effect in either location. Nuclear proteins
      bound the cad +55/+75 element in a cell cycle-dependent manner in electromobility
      shift assays; antibodies specific to USF and Max blocked the DNA-binding activity
      of different growth-regulated protein-DNA complexes. Expression of c-Myc mutants
      which have been shown to dominantly interfere with the function of c-Myc and Max
      significantly inhibited cad transcription during S phase but had no effect on
      transcription from another G1/S-phase-activated promoter, dhfr. These data
      support a model whereby E-box-binding proteins activate serum-induced
      transcription from the cad promoter at the G1/S-phase boundary and suggest that a
      Max-associated protein complex contributes to the serum response.

PMID- 7739538
TI  - Ligand-independent activation of the platelet-derived growth factor beta
      receptor: requirements for bovine papillomavirus E5-induced mitogenic signaling.
AB  - The E5 protein of bovine papillomavirus type 1 binds to and activates the
      endogenous platelet-derived growth factor (PDGF) beta receptor in fibroblasts,
      resulting in cell transformation. We have developed a functional assay to test
      the ability of PDGF beta receptor mutants to mediate a mitogenic signal initiated
      by the E5 protein. Lymphoid Ba/F3 cells are strictly dependent on interleukin-3
      for growth, but coexpression of the wild-type PDGF beta receptor and the E5 or v
      sis-encoded protein generated a mitogenic signal which allowed Ba/F3-derived
      cells to proliferate in the absence of interleukin-3. In these cells, the E5
      protein bound to and caused increased tyrosine phosphorylation of both the mature
      and the precursor forms of the wild-type PDGF beta receptor. The tyrosine kinase
      activity of the receptor was necessary for E5-induced receptor tyrosine
      phosphorylation and mitogenic activity but not for complex formation with the E5
      protein. In contrast, the PDGF-binding domain of the receptor was not required
      for complex formation with the E5 protein, E5-induced tyrosine phosphorylation or
      mitogenic activity, demonstrating that E5-mediated receptor activation is ligand
      independent. Analysis of receptor mutants lacking various combinations of
      tyrosine phosphorylation sites revealed that the E5 and v-sis-encoded proteins
      display similar requirements for signaling and suggested that the wild-type PDGF
      beta receptor can generate multiple independent mitogenic signals. Importantly,
      these mutants dissociated two activities of the PDGF beta receptor tyrosine
      kinase, both of which are required for sustained mitogenic signaling: (i)
      receptor autophosphorylation and creation of binding sites for SH2 domain
      containing proteins and (ii) phosphorylation of substrates other than the
      receptor itself.

PMID- 7739539
TI  - Dual DNA binding specificity of ADD1/SREBP1 controlled by a single amino acid in
      the basic helix-loop-helix domain.
AB  - Adipocyte determination- and differentiation-dependent factor 1 (ADD1), a member
      of the basic helix-loop-helix (bHLH) family of transcription factors, has been
      associated with both adipocyte differentiation and cholesterol homeostasis (in
      which case it has been termed SREBP1). Using PCR-amplified binding analysis, we
      demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both
      an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be
      important in cholesterol metabolism, sterol regulatory element 1 (SRE-1;
      ATCACCCCAC). The ADD1/SREBP1 consensus E-box site is similar to a regulatory
      sequence designated the carbohydrate response element, defined by its ability to
      regulate transcription in response to carbohydrate in genes involved in fatty
      acid and triglyceride metabolism in liver and fat. When expressed in fibroblasts,
      ADD1/SREBP1 activates transcription through both the carbohydrate response E-box
      element and SRE-1. Substitution of an atypical tyrosine in the basic region of
      ADD1/SREBP1 to an arginine found in most bHLH protein causes a restriction to
      only E-box binding. Conversely, substitution of a tyrosine for the equivalent
      arginine in another bHLH protein, upstream stimulatory factor, allows this factor
      to acquire a dual binding specificity similar to that of ADD1/SREBP1. Promoter
      activation by ADD1/SREBP1 through the carbohydrate response element E box is not
      sensitive to the tyrosine-to-arginine mutation, while activation through SRE-1 is
      completely suppressed. These data illustrate that ADD1/SREBP1 has dual DNA
      sequence specificity controlled by a single amino acid residue; this dual
      specificity may provide a novel mechanism to coordinate different pathways of
      lipid metabolism.

PMID- 7739540
TI  - The Schizosaccharomyces pombe MBF complex requires heterodimerization for entry
      into S phase.
AB  - In Schizosaccharomyces pombe, MBF is a DNA-binding complex suspected to activate
      the transcription of genes necessary for entry into S phase. The MBF complex
      contains both p85cdc10 and p72res1/sct1. To obtain a better understanding of how
      the MBF complex regulates gene expression at the G1/S transition, we have
      performed a genetic analysis of p72res1. We determined that p72res1 can bind
      specifically to the cdc22 promoter, when analyzed by gel mobility shift assay,
      and that the N-terminal 157 amino acids of p72res1 are sufficient for this
      specific binding. When overexpressed in vivo, a fragment of p72res1 containing
      this DNA-binding domain could rescue a strain carrying a temperature-sensitive
      cdc10 allele at the restrictive temperature as well as a strain with a cdc10 null
      allele. We also determined that the C-terminal region of p72res1 is necessary and
      sufficient for binding to p85cdc10. Overexpression of the cdc10-binding domain of
      p72res1 leads to a G1 arrest with a cdc phenotype and a decrease on MBF activity.
      Overexpression of full-length p72res1 also leads to a growth arrest that can be
      rescued by overexpression of p85cdc10. These results imply that the MBF activity
      in vivo is dependent on the interaction of p85cdc10 with p72res1.

PMID- 7739541
TI  - Cyclin D1 is dispensable for G1 control in retinoblastoma gene-deficient cells
      independently of cdk4 activity.
AB  - To elucidate the regulator-versus-target relationship in the cyclin
      D1/cdk4/retinoblastoma protein (pRB) pathway, we examined fibroblasts from RB-1
      gene-deficient and RB-1 wild-type littermate mouse embryos (ME) and in human
      tumor cell lines that differed in the status of the RB-1 gene. The RB+/+ and RB-/
      ME fibroblasts expressed similar protein levels of D-type cyclins, cdk4, and
      cdk6, showed analogous spectra and abundance of cellular proteins complexed with
      cdk4 and/or cyclins D1 and D2, and exhibited comparable associated kinase
      activities. Of the two human cell lines established from the same sarcoma biopsy,
      the RB-positive SKUT1B cells contained cdk4 that was mainly associated with D
      type cyclins, contrary to a predominant cdk4-p16INK4 complex in the RB-deficient
      SKUT1A cells. Antibody-mediated neutralization of cyclin D1 arrested the RB
      positive ME and SKUT1B cells in G1, whereas this cyclin appeared dispensable in
      the RB-deficient ME and SKUT1A cells. Lack of requirement for cyclin D1 therefore
      correlated with absence of functional pRB, regardless of whether active cyclin
      D1/cdk4 holoenzyme was present in the cells under study. Consistent with a
      potential role of cyclin D/cdk4 in phosphorylation of pRB, monoclonal anti-cyclin
      D1 antibodies supporting the associated kinase activity failed to significantly
      affect proliferation of RB-positive cells, whereas the antibody DCS-6, unable to
      coprecipitate cdk4, efficiently inhibited G1 progression and prevented pRB
      phosphorylation in vivo. These data provide evidence for an upstream control
      function of cyclin D1/cdk4, and a downstream role for pRB, in the order of events
      regulating transition through late G1 phase of the mammalian cell division cycle.

PMID- 7739543
TI  - Identification of distinct classes and functional domains of Wnts through
      expression of wild-type and chimeric proteins in Xenopus embryos.
AB  - Wnts are secreted signaling factors which influence cell fate and cell behavior
      in developing embryos. Overexpression in Xenopus laevis embryos of a Xenopus Wnt,
      Xwnt-8, leads to a duplication of the embryonic axis. In embryos ventralized by
      UV irradiation, Xwnt-8 restores expression of the putative transcription factor
      goosecoid, and rescues normal axis formation. In contrast, overexpression of Xwnt
      5A in normal embryos generates defects in dorsoanterior structures, without
      inducing goosecoid or a secondary axis. To determine whether Xwnt-4 and Xwnt-11
      fall into one of these two previously described classes of activity, synthetic
      mRNAs were introduced into animal caps, normal embryos, and UV-treated embryos.
      The results indicate that Xwnt-4, Xwnt-5A, and Xwnt-11 are members of a single
      functional class with activities that are indistinguishable in these assays. To
      investigate whether distinct regions of Xwnt-8 and Xwnt-5A were sufficient for
      eliciting the observed effects of overexpression, we generated a series of
      chimeric Xwnts. RNAs encoding the chimeras were injected into normal and UV
      irradiated Xenopus embryos. Analysis of the embryonic phenotypes and goosecoid
      levels reveals that chimeras composed of carboxy-terminal regions of Xwnt-8 and
      amino-terminal regions of Xwnt-5A are indistinguishable from the activities of
      native Xwnt-8 and that are the reciprocal chimeras elicit effects
      indistinguishable from overexpression of native Xwnt-5A. We conclude that the
      carboxy-terminal halves of these Xwnts are candidate domains for specifying
      responses to Xwnt signals.

PMID- 7739542
TI  - Human cyclin E, a nuclear protein essential for the G1-to-S phase transition.
AB  - Cyclin E was first identified by screening human cDNA libraries for genes that
      would complement G1 cyclin mutations in Saccharomyces cerevisiae and has
      subsequently been found to have specific biochemical and physiological properties
      that are consistent with it performing a G1 function in mammalian cells. Most
      significantly, the cyclin E-Cdk2 complex is maximally active at the G1/S
      transition, and overexpression of cyclin E decreases the time it takes the cell
      to complete G1 and enter S phase. We have now found that mammalian cells express
      two forms of cyclin E protein which differ from each other by the presence or
      absence of a 15-amino-acid amino-terminal domain. These proteins are encoded by
      alternatively spliced mRNAs and are localized to the nucleus during late G1 and
      early S phase. Fibroblasts engineered to constitutively overexpress either form
      of cyclin E showed elevated cyclin E-dependent kinase activity and a shortened G1
      phase of the cell cycle. The overexpressed cyclin E protein was detected in the
      nucleus during all cell cycle phases, including G0. Although the cyclin E protein
      could be overexpressed in quiescent cells, the cyclin E-Cdk2 complex was
      inactive. It was not activated until 6 to 8 h after readdition of serum, 4 h
      earlier than the endogenous cyclin E-Cdk2. This premature activation of cyclin E
      Cdk2 was consistent with the extent of G1 shortening caused by cyclin E
      overexpression. Microinjection of affinity-purified anti-cyclin E antibodies
      during G1 inhibited entry into S phase, whereas microinjection performed near the
      G1/S transition was ineffective. These results demonstrate that cyclin E is
      necessary for entry into S phase. Moreover, we found that cyclin E, in contrast
      to cyclin D1, was required for the G1/S transition even in cells lacking
      retinoblastoma protein function. Therefore, cyclins E and D1 control two
      different transitions within the human cell cycle.

PMID- 7739544
TI  - The GCR1 requirement for yeast glycolytic gene expression is suppressed by
      dominant mutations in the SGC1 gene, which encodes a novel basic-helix-loop-helix
      protein.
AB  - The GCR1 gene product is required for maximal transcription of yeast glycolytic
      genes and for growth of yeast strains in media containing glucose as a carbon
      source. Dominant mutations in two genes, SGC1 and SGC2, as well as recessive
      mutations in the SGC5 gene were identified as suppressors of the growth and
      transcriptional defects caused by a gcr1 null mutation. The wild-type and mutant
      alleles of SGC1 were cloned and sequenced. The predicted amino acid sequence of
      the SGC1 gene product includes a region with substantial similarity to the basic
      helix-loop-helix domain of the Myc family of DNA-binding proteins. The SGC1-1
      dominant mutant allele contained a substitution of glutamine for a highly
      conserved glutamic acid residue within the putative basic DNA binding domain. A
      second dominant mutant, SGC1-2, contained a valine-for-isoleucine substitution
      within the putative loop region. The SGC1-1 dominant mutant suppressed the GCR1
      requirement for enolase, glyceraldehyde-3-phosphate dehydrogenase,
      phosphoglycerate kinase, phosphoglycerate mutase, and pyruvate kinase gene
      expression. Expression of the yeast enolase genes was reduced three- to fivefold
      in strains carrying an sgc1 null mutation, demonstrating that SGC1 is required
      for maximal enolase gene expression. Expression of the enolase genes in strains
      carrying gcr1 and sgc1 double null mutations was substantially less than observed
      for strains carrying either null mutation alone, suggesting that GCR1 and SGC1
      function on parallel pathways to activate yeast glycolytic gene expression.

PMID- 7739545
TI  - Cyclophilin 20 is involved in mitochondrial protein folding in cooperation with
      molecular chaperones Hsp70 and Hsp60.
AB  - We studied the role of mitochondrial cyclophilin 20 (CyP20), a peptidyl-prolyl
      cis-trans isomerase, in preprotein translocation across the mitochondrial
      membranes and protein folding inside the organelle. The inhibitory drug
      cyclosporin A did not impair membrane translocation of preproteins, but it
      delayed the folding of an imported protein in wild-type mitochondria. Similarly,
      Neurospora crassa mitochondria lacking CyP20 efficiently imported preproteins
      into the matrix, but folding of an imported protein was significantly delayed,
      indicating that CyP20 is involved in protein folding in the matrix. The slow
      folding in the mutant mitochondria was not inhibited by cyclosporin A. Folding
      intermediates of precursor molecules reversibly accumulated at the molecular
      chaperones Hsp70 and Hsp60 in the matrix. We conclude that CyP20 is a component
      of the mitochondrial protein folding machinery and that it cooperates with Hsp70
      and Hsp60. It is speculated that peptidyl-prolyl cis-trans isomerases in other
      cellular compartments may similarly promote protein folding in cooperation with
      chaperone proteins.

PMID- 7739546
TI  - Genetic selection for balanced retroviral splicing: novel regulation involving
      the second step can be mediated by transitions in the polypyrimidine tract.
AB  - Incomplete splicing is essential for retroviral replication; and in simple
      retroviruses, splicing regulation appears to occur entirely in cis. Our previous
      studies, using avian sarcoma virus, indicated that weak splicing signals allow
      transcripts to escape the splicing pathway. We also isolated a series of avian
      sarcoma virus mutants in which env mRNA splicing was regulated by mechanisms
      distinct from those of the wild-type virus. In vitro splicing experiments with
      one such mutant (insertion suppressor 1 [IS1]) revealed that exon 1 and lariat
      exon 2 intermediates were produced (step 1) but the exons were not efficiently
      ligated (step 2). In this work, we have studied the mechanism of this second-step
      block as well as its biological relevance. Our results show that the second-step
      block can be overcome by extending the polypyrimidine tract, and this causes an
      oversplicing defect in vivo. The requirement for regulated splicing was exploited
      to isolate new suppressor mutations that restored viral growth by down-regulating
      splicing. One suppressor consisted of a single U-to-C transition in the
      polypyrimidine tract; a second included this same change as well as an additional
      U-to-C transition within a uridine stretch in the polypyrimidine tract. These
      suppressor mutations affected primarily the second step of splicing in vitro.
      These results support a specific role for the polypyrimidine tract in the second
      step of splicing and confirm that, in a biological system, uridines and cytosines
      are not functionally equivalent within the polypyrimidine tract. Unlike the wild
      type virus, the second-step mutants displayed significant levels of lariat-exon 2
      in vivo, suggesting a role for splicing intermediates in regulation. Our results
      indicate that splicing regulation can involve wither the first or second step.

PMID- 7739547
TI  - Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D
      dependent kinases CDK4 and CDK6.
AB  - Cyclin D-dependent kinases act as mitogen-responsive, rate-limiting controllers
      of G1 phase progression in mammalian cells. Two novel members of the mouse INK4
      gene family, p19 and p18, that specifically inhibit the kinase activities of CDK4
      and CDK6, but do not affect those of cyclin E-CDK2, cyclin A-CDK2, or cyclin B
      CDC2, were isolated. Like the previously described human INK4 polypeptides,
      p16INK4a/MTS1 and p15INK4b/MTS2, mouse p19 and p18 are primarily composed of
      tandemly repeated ankyrin motifs, each ca. 32 amino acids in length, p19 and p18
      bind directly to CDK4 and CDK6, whether untethered or in complexes with D
      cyclins, and can inhibit the activity of cyclin D-bound cyclin-dependent kinases
      (CDKs). Although neither protein interacts with D cyclins or displaces them from
      preassembled cyclin D-CDK complexes in vitro, both form complexes with CDKs at
      the expense of cyclins in vivo, suggesting that they may also interfere with
      cyclin-CDK assembly. In proliferating macrophages, p19 mRNA and protein are
      periodically expressed with a nadir in G1 phase and maximal synthesis during S
      phase, consistent with the possibility that INK4 proteins limit the activities of
      CDKs once cells exit G1 phase. However, introduction of a vector encoding p19
      into mouse NIH 3T3 cells leads to constitutive p19 synthesis, inhibits cyclin D1
      CDK4 activity in vivo, and induces G1 phase arrest.

PMID- 7739548
TI  - Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with
      homology to p16ink4.
AB  - The cell cycle in mammalian cells is regulated by a series of cyclins and cyclin
      dependent kinases (CDKs). The G1/S checkpoint is mainly dictated by the kinase
      activities of the cyclin D-CDK4 and/or cyclin D-CDK6 complex and the cyclin E
      CDK2 complex. These G1 kinases can in turn be regulated by cell cycle inhibitors,
      which may cause the cells to arrest at the G1 phase. In T-cell hybridomas,
      addition of anti-T-cell receptor antibody results not only in G1 arrest but also
      in apoptosis. In searching for a protein(s) which might interact with Nur77, an
      orphan steroid receptor required for activation-induced apoptosis of T-cell
      hybridomas, we have cloned a novel human and mouse CDK inhibitor, p19. The
      deduced p19 amino acid sequence consists of four ankyrin repeats with 48%
      identity to p16. The human p19 gene is located on chromosome 19p13, distinct from
      the positions of p18, p16, and p15. Its mRNA is expressed in all cell types
      examined. The p19 fusion protein can associate in vitro with CDK4 but not with
      CDK2, CDC2, or cyclin A, B, E, or D1 to D3. Addition of p19 protein can lead to
      inhibition of the in vitro kinase activity of cyclin D-CDK4 but not that of
      cyclin E-CDK2. In T-cell hybridoma DO11.10, p19 was found in association with
      CDK4 and CDK6 in vivo, although its association with Nur77 is not clear at this
      point. Thus, p19 is a novel CDK inhibitor which may play a role in the cell cycle
      regulation of T cells.

PMID- 7739549
TI  - Inducible nuclear expression of newly synthesized I kappa B alpha negatively
      regulates DNA-binding and transcriptional activities of NF-kappa B.
AB  - The transcription factor NF-kappa B is exploited by many viruses, including the
      human immunodeficiency virus, for expression of viral genes, but its primary role
      appears to be in the rapid induction of cellular genes during immune and
      inflammatory responses. The inhibitor protein I kappa B alpha maintains NF-kappa
      B in an inactive form in the cytoplasms of unstimulated cells, but upon cell
      activation, I kappa B alpha is rapidly degraded, leading to nuclear translocation
      of free NF-kappa B. However, NF-kappa B-dependent transcription of the I kappa B
      alpha gene leads to rapid resynthesis of the I kappa B alpha protein and
      inhibition of NF-kappa B-dependent transcription. Here we demonstrate a new
      regulatory function of I kappa B alpha exerted on NF-kappa B in the nuclear
      compartment. Although normally found in the cytoplasm, I kappa B alpha, newly
      synthesized in response to tumor necrosis factor or interleukin I, is transported
      to the nucleus. In the nucleus I kappa B alpha associates with the p50 and p65
      subunits of NF-kappa B, inhibiting DNA binding of the transcription factor.
      Furthermore, nuclear expression of I kappa B alpha correlates with transcription
      termination of transfected NF-kappa B-dependent luciferase genes. Following the
      appearance of I kappa B alpha in the nuclei of activated cells, a dramatic
      reduction in the amount of nuclear p50 occurs, suggesting that NF-kappa B-I kappa
      B alpha complexes are cleared from the nucleus.

PMID- 7739550
TI  - NFATx, a novel member of the nuclear factor of activated T cells family that is
      expressed predominantly in the thymus.
AB  - The nuclear factor of activated T cells (NFAT) regulates cytokine gene expression
      in T cells through cis-acting elements located in the promoters of cytokine
      genes. Here, we report the cDNA cloning, chromosomal localization, and initial
      characterization of a transcription factor related to NFATp and NFATc. The novel
      molecule, designated NFATx, exhibits in its middle a region very similar to the
      Rel homology domain in NFATc and NFATp. The amino-terminal region of NFATx also
      shows significant similarities to corresponding sequences in NFATc and NFATp and
      contains three copies of a conspicuous 17-residue motif of unknown function. We
      provide evidence showing that NFATx can reconstitute binding to the NFAT-binding
      site from the interleukin 2 promoter when combined with AP1 (c-Fos/c-Jun)
      polypeptides and that NFATx is capable of activating transcription of the
      interleukin 2 promoter in COS-7 cells when stimulated with phorbol ester and
      calcium ionophore. NFATx mRNA is preferentially and remarkably found in the
      thymus and at lower levels in peripheral blood leukocytes. The expression pattern
      of NFATx, together with its functional activity, strongly suggests that NFATx
      plays a role in the regulation of gene expression in T cells and immature
      thymocytes.

PMID- 7739551
TI  - Myogenin and MEF2 function synergistically to activate the MRF4 promoter during
      myogenesis.
AB  - The basic helix-loop-helix muscle regulatory factor (MRF) gene family encodes
      four distinct muscle-specific transcription factors known as MyoD, myogenin, Myf
      5, and MRF4. These proteins represent key regulatory factors that control many
      aspects of skeletal myogenesis. Although the MRFs often exhibit overlapping
      functional activities, their distinct expression patterns during embryogenesis
      suggest that each protein plays a unique role in controlling aspects of muscle
      development. As a first step in determining how MRF4 gene expression is
      developmentally regulated, we examined the ability of the MRF4 gene to be
      expressed in a muscle-specific fashion in vitro. Our studies show that the
      proximal MRF4 promoter contains sufficient information to direct muscle-specific
      expression. Located within the proximal promoter are a single MEF2 site and E box
      that are required for maximum MRF4 expression. Mutation of the MEF2 site or E box
      severely impairs the ability of this promoter to produce a muscle-specific
      response. In addition, the MEF2 site and E box function in concert to
      synergistically activate the MRF4 gene in nonmuscle cells coexpressing MEF2 and
      myogenin proteins. Thus, the MRF4 promoter is regulated by the MEF2 and basic
      helix-loop-helix MRF protein family through a cross-regulatory circuitry.
      Surprisingly, the MRF4 promoter itself is not transactivated by MRF4, suggesting
      that this MRF gene is not subject to an autoregulatory pathway as previously
      implied by other studies. Understanding the molecular mechanisms regulating
      expression of each MRF gene is central to fully understanding how these factors
      control developmental events.

PMID- 7739553
TI  - Regulation and intracellular localization of Saccharomyces cerevisiae strand
      exchange protein 1 (Sep1/Xrn1/Kem1), a multifunctional exonuclease.
AB  - The Saccharomyces cerevisiae strand exchange protein 1 (Sep1; also referred to as
      Xrn1, Kem1, Rar5, or Stp beta) catalyzes the formation of hybrid DNA from model
      substrates in vitro. The protein is also a 5'-to-3' exonuclease active on DNA and
      RNA. Multiple roles for the in vivo function of Sep1, ranging from DNA
      recombination and cytoskeleton to RNA turnover, have been proposed. We show that
      Sep1 is an abundant protein in vegetative S. cerevisiae cells, present at about
      80,000 molecules per diploid cell. Protein levels were not changed during the
      cell cycle or in response to DNA-damaging agents but increased twofold during
      meiosis. Cell fractionation and indirect immunofluorescence studies indicated
      that > 90% of Sep1 was cytoplasmic in vegetative cells, and indirect
      immunofluorescence indicated a cytoplasmic localization in meiotic cells as well.
      The localization supports the proposal that Sep1 has a role in cytoplasmic RNA
      metabolism. Anti-Sep1 monoclonal antibodies detected cross-reacting antigens in
      the fission yeast Schizosccharomyces pombe, in Drosophila melanogaster embryos,
      in Xenopus laevis, and in a mouse pre-B-cell line.

PMID- 7739552
TI  - Synthetic lethality of sep1 (xrn1) ski2 and sep1 (xrn1) ski3 mutants of
      Saccharomyces cerevisiae is independent of killer virus and suggests a general
      role for these genes in translation control.
AB  - Strand exchange protein 1 (Sep1) (also referred to as exoribonuclease I [Xrn1])
      from Saccharomyces cerevisiae has been implicated in DNA recombination, RNA
      turnover, karyogamy, and G4 DNA pairing among other disparate cellular processes.
      Using a genetic approach to study the role of SEP1/XRN1 in mitotic yeast cells,
      we identified mutations in the genes superkiller 2 (SKI2) and superkiller 3
      (SKI3) as synthetically lethal with an sep1 null mutation. The SKI genes are
      thought to comprise an intracellular antiviral system controlling the expression
      of killer toxin from double-stranded RNA virus found in many yeast strains.
      However, the lethality of sep1 ski2 and sep1 ski3 mutants was independent of the
      L-A and M viruses, suggesting that the SKI genes act in a general cellular
      process in addition to virus control. We propose that Sep1/Xrn1 and Ski2 both act
      to block translation on transcripts targeted for degradation. Using a temperature
      sensitive allele of SEP1/XRN1, we show that double mutants display a synthetic
      cell cycle arrest in late G1 at Start.

PMID- 7739554
TI  - Dynamic protein-DNA architecture of a yeast heat shock promoter.
AB  - Here we present an in vivo footprinting analysis of the Saccharomyces cerevisiae
      HSP82 promoter. Consistent with current models, we find that yeast heat shock
      factor (HSF) binds to strong heat shock elements (HSEs) in non-heat-shocked
      cells. Upon heat shock, however, additional binding of HSF becomes apparent at
      weak HSEs of the promoter as well. Recovery from heat shock results in a dramatic
      reduction in HSF binding at both strong and weak HSEs, consistent with a model in
      which HSF binding is subject to a negative feedback regulation by heat shock
      proteins. In vivo KMnO4 footprinting reveals that the interaction of the TATA
      binding protein (TBP) with this promoter is also modulated: heat shock slightly
      increases TBP binding to the promoter and this binding is reduced upon recovery
      from heat shock. KMnO4 footprinting does not reveal a high density of polymerase
      at the promoter prior to heat shock, but a large open complex between the
      transcriptional start site and the TATA box is formed rapidly upon activation,
      similar to that observed in other yeast genes.

PMID- 7739555
TI  - DNA-binding and chromatin localization properties of CHD1.
AB  - CHD1 is a novel DNA-binding protein that contains both a chromatin organization
      modifier (chromo) domain and a helicase/ATPase domain. We show here that CHD1
      preferentially binds to relatively long A.T tracts in double-stranded DNA via
      minor-groove interactions. Several CHD1-binding sites were found in a well
      characterized nuclear-matrix attachment region, which is located adjacent to the
      intronic enhancer of the kappa immunoglobulin gene. The DNA-binding activity of
      CHD1 was localized to a 229-amino-acid segment in the C-terminal portion of the
      protein, which contains sequence motifs that have previously been implicated in
      the minor-groove binding of other proteins. We also demonstrate that CHD1 is a
      constituent of bulk chromatin and that it can be extracted from nuclei with 0.6 M
      NaCl or with 2 mM EDTA after mild digestion with micrococcal nuclease. In
      contrast to another chromo-domain protein, HP1, CHD1 is not preferentially
      located in condensed centromeric heterochromatin, even though centromeric DNA is
      highly enriched in (A+T)-rich tracts. Most interestingly, CHD1 is released into
      the cytoplasm when cells enter mitosis and is reincorporated into chromatin
      during telophase-cytokinesis. These observations lend credence to the idea that
      CHD1, like other proteins with chromo or helicase/ATPase domains, plays an
      important role in the determination of chromatin architecture.

PMID- 7739556
TI  - Isolation and characterization of a novel mitogenic regulatory gene, 322, which
      is transcriptionally suppressed in cells transformed by src and ras.
AB  - In an attempt to isolate novel regulatory and/or tumor suppressor genes, we
      identified cDNAs whose abundance is low in NIH 3T3 cells and further decreased
      following the expression of the activated oncogene, v-src. The transcription of
      one such gene, 322, is suppressed at least 15-fold in src-, ras-, and fos
      transformed cells and 3-fold in myc-transformed cells but is unaffected in raf-,
      mos-, or neu-transformed cells. Activation of a ts-v-src allele in confluent 3Y1
      fibroblasts resulted in an initial increase in 322 mRNA levels after 1 to 2 h
      followed by a rapid decrease to suppressed levels after 4 to 8 h. Morphological
      transformation was not detected until 12 h later, indicating that the
      accumulation of 322 transcripts is regulated by v-src and not as a consequence of
      transformation. Addition of fetal calf serum to starved subconfluent NIH 3T3 or
      3Y1 fibroblasts resulted in a similar biphasic regulation of 322, indicating that
      322 transcription is responsive to mitogenic factors. Sequence analysis of a
      putative full-length 322 cDNA clone (5.4 kb) identified a large open reading
      frame (ORF) encoding a 148.1-kDa product. In vitro transcription and translation
      of the 322 cDNA from a T7 promoter resulted in a 207-kDa product whose
      electrophoretic mobility on a sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis gel was unaffected by digestion with endoglycosidase F. The
      discrepancy in predicted versus measured molecular weights may result from the
      high percentage of acidic residues (roughly 20% Glu or Asp) in the 322 ORF
      product. Comparison of the 322 cDNA ORF with sequences in data banks indicates
      that this gene is novel. The 322 ORF product contains a potential Cys-1-His-3 Zn
      finger, at least five nuclear localization signals of the adenovirus E1a motif
      K(R/K)X(R/K), and alternating acidic and basic domains. Overexpression of the 322
      cells resulted in the selection of rapidly growing cells which had lost the
      transduced 322 cDNA. Thus, 322 represent a novel src- and ras-regulated gene
      which encodes a potential regulator of mitogenesis and/or tumor suppressor.

PMID- 7739557
TI  - Decoying the cap- mRNA degradation system by a double-stranded RNA virus and
      poly(A)- mRNA surveillance by a yeast antiviral system.
AB  - The major coat protein of the L-A double-stranded RNA virus of Saccharomyces
      cerevisiae covalently binds m7 GMP from 5' capped mRNAs in vitro. We show that
      this cap binding also occurs in vivo and that, while this activity is required
      for expression of viral information (killer toxin mRNA level and toxin
      production) in a wild-type strain, this requirement is suppressed by deletion of
      SKI1/XRN1/SEP1. We propose that the virus creates decapped cellular mRNAs to
      decoy the 5'-->3' exoribonuclease specific for cap- RNA encoded by XRN1. The SKI2
      antiviral gene represses the copy numbers of the L-A and L-BC viruses and the 20S
      RNA replicon, apparently by specifically blocking translation of viral RNA. We
      show that SKI2, SKI3, and SKI8 inhibit translation of electroporated luciferase
      and beta-glucuronidase mRNAs in vivo, but only if they lack the 3' poly(A)
      structure. Thus, L-A decoys the SKI1/XRN1/SEP1 exonuclease directed at 5'
      uncapped ends, but translation of the L-A poly(A)- mRNA is repressed by
      Ski2,3,8p. The SKI2-SKI3-SKI8 system is more effective against cap+ poly(A)-
      mRNA, suggesting a (nonessential) role in blocking translation of fragmented
      cellular mRNAs.

PMID- 7739558
TI  - Yeast virus propagation depends critically on free 60S ribosomal subunit
      concentration.
AB  - Over 30 MAK (maintenance of killer) genes are necessary for propagation of the
      killer toxin-encoding M1 satellite double-stranded RNA of the L-A virus. Sequence
      analysis revealed that MAK7 is RPL4A, one of the two genes encoding ribosomal
      protein L4 of the 60S subunit. We further found that mutants with mutations in 18
      MAK genes (including mak1 [top1], mak7 [rpl4A], mak8 [rpl3], mak11, and mak16)
      had decreased free 60S subunits. Mutants with another three mak mutations had
      half-mer polysomes, indicative of poor association of 60S and 40S subunits. The
      rest of the mak mutants, including the mak3 (N-acetyltransferase) mutant, showed
      a normal profile. The free 60S subunits, L-A copy number, and the amount of L-A
      coat protein in the mak1, mak7, mak11, and mak16 mutants were raised to the
      normal level by the respective normal single-copy gene. Our data suggest that
      most mak mutations affect M1 propagation by their effects on the supply of
      proteins from the L-A virus and that the translation of the non-poly(A) L-A mRNA
      depends critically on the amount of free 60S ribosomal subunits, probably because
      60S association with the 40S subunit waiting at the initiator AUG is facilitated
      by the 3' poly(A).

PMID- 7739559
TI  - Upstream stimulatory factor regulates expression of the cell cycle-dependent
      cyclin B1 gene promoter.
AB  - Progression through the somatic cell cycle requires the temporal regulation of
      cyclin gene expression and cyclin protein turnover. One of the best-characterized
      examples of this regulation is seen for the B-type cyclins. These cyclins and
      their catalytic component, cdc2, have been shown to mediate both the entry into
      and maintenance of mitosis. The cyclin B1 gene has been shown to be expressed
      between the late S and G2 phases of the cell cycle, while the protein is degraded
      specifically at interphase via ubiquitination. To understand the molecular basis
      for transcriptional regulation of the cyclin B1 gene, we cloned the human cyclin
      B1 gene promoter region. Using a chloramphenicol acetyltransferase reporter
      system and both stable and transient assays, we have shown that the cyclin B1
      gene promoter (extending to -3800 bp relative to the cap site) can confer G2
      enhanced promoter activity. Further analysis revealed that an upstream
      stimulatory factor (USF)-binding site and its cognate transcription factor(s) are
      critical for expression from the cyclin B1 promoter in cycling HeLa cells.
      Interestingly, USF DNA-binding activity appears to be regulated in a G2-specific
      fashion, supporting the idea that USF may play some role in cyclin B1 gene
      activation. These studies suggest an important link between USF and the cyclin B1
      gene, which in part explains how maturation promoting factor complex formation is
      regulated.

PMID- 7739560
TI  - Insulin-stimulated disassociation of the SOS-Grb2 complex.
AB  - Insulin stimulation of differentiated 3T3-L1 adipocytes or Chinese hamster ovary
      cells expressing high levels of the insulin receptor resulted in a time-dependent
      decrease in the electrophoretic mobility of SOS on sodium dodecyl sulfate
      polyacrylamide gels. The reduction in SOS mobility was completely reversed by
      alkaline phosphatase treatment, and the in vitro phosphorylation of SOS by
      mitogen-activated protein kinase resulted in a decrease of electrophoretic
      mobility identical to that following in vivo insulin stimulation.
      Immunoprecipitation of Grb2 followed by SOS immunoblotting demonstrated a
      disassociation of the SOS-Grb2 complex that paralleled the decrease in SOS
      electrophoretic mobility. Similarly, SOS immunoprecipitation followed by Grb2
      immunoblotting also indicated an uncoupling of the SOS-Grb2 complex. Further,
      incubation of whole-cell extracts with glutathione-S-transferase-Grb2 fusion
      proteins demonstrated that insulin stimulation resulted in a decreased affinity
      of SOS for Grb2. In contrast, the dissociation of SOS from Grb2 did not affect
      the interactions between Grb2 and tyrosine-phosphorylated Shc. In addition to
      insulin, several other agents which activate the mitogen-activated protein kinase
      pathway (platelet-derived growth factor, serum, and phorbol ester) also resulted
      in the uncoupling of the SOS-Grb2 complex. Consistent with these results,
      expression of v-ras and v-raf resulted in a constitutive decrease in the
      association between SOS and Grb2. Together, these data suggest a molecular
      mechanism accounting for the transient activation of ras due to the uncoupling of
      the SOS-Grb2 complex following SOS phosphorylation.

PMID- 7739561
TI  - In vivo and in vitro arginine methylation of RNA-binding proteins.
AB  - Heterogenous nuclear ribonucleoproteins (hnRNPs) bind pre-mRNAs and facilitate
      their processing into mRNAs. Many of the hnRNPs undergo extensive
      posttranslational modifications including methylation on arginine residues.
      hnRNPs contain about 65% of the total NG,NG-dimethylarginine found in the cell
      nucleus. The role of this modification is not known. Here we identify the hnRNPs
      that are methylated in HeLa cells and demonstrate that most of the pre-mRNA
      binding proteins receive this modification. Using recombinant human hnRNP A1 as a
      substrate, we have partially purified and characterized a protein-arginine N
      methyltransferase specific for hnRNPs from HeLa cells. This methyltransferase can
      methylate the same subset of hnRNPs in vitro as are methylated in vivo.
      Furthermore, it can also methylate other RNA-binding proteins that contain the
      RGG motif RNA-binding domain. This activity is evolutionarily conserved from
      lower eukaryotes to mammals, suggesting that methylation has a significant role
      in the function of RNA-binding proteins.

PMID- 7739562
TI  - Coupling of a signal response domain in I kappa B alpha to multiple pathways for
      NF-kappa B activation.
AB  - The eukaryotic transcription factor NF-kappa B plays a central role in the
      induced expression of human immunodeficiency virus type 1 and in many aspects of
      the genetic program mediating normal T-cell activation and growth. The nuclear
      activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by
      an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is
      rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B
      inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral
      transactivators such as the Tax protein of human T-cell leukemia virus type 1. To
      explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we
      identified novel mutants of I kappa B alpha that uncouple its inhibitory and
      signal-transducing functions in human T lymphocytes. Specifically, removal of the
      N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to
      form latent complexes with NF-kappa B in the cytoplasm. However, this deletion
      mutation prevented the induced phosphorylation, degradative loss, and functional
      release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine
      substitutions introduced at two serine residues positioned within this N-terminal
      regulatory region of I kappa B alpha also yielded constitutive repressors that
      escaped from Tax-induced turnover and that potently inhibited immune activation
      pathways for NF-kappa B induction, including those initiated from antigen and
      cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these
      sites rectified this functional defect, a finding consistent with a causal
      linkage between the phosphorylation status and proteolytic stability of this
      cytoplasmic inhibitor. Together, these in vivo studies define a critical signal
      response domain in I kappa B alpha that coordinately controls the biologic
      activities of I kappa B alpha and NF-kappa B in response to viral and immune
      stimuli.

PMID- 7739563
TI  - Identification of Tyr-397 as the primary site of tyrosine phosphorylation and
      pp60src association in the focal adhesion kinase, pp125FAK.
AB  - A number of cellular processes, such as proliferation, differentiation, and
      transformation, are regulated by cell-extracellular matrix interactions. Previous
      studies have identified a novel tyrosine kinase, the focal adhesion kinase
      p125FAK, as a component of cell adhesion plaques. p125FAK was identified as a 125
      kDa tyrosine-phosphorylated protein in cells transformed by the v-src oncogene.
      p125FAK is an intracellular protein composed of three domains: a central domain
      with homology to protein tyrosine kinases, flanked by two noncatalytic domains of
      400 amino acids which bear no significant homology to previously cloned proteins.
      p125FAK is believed to play an important regulatory role in cell adhesion because
      it localizes to cell adhesion plaques and because its phosphorylation on tyrosine
      residues is regulated by binding of cell surface integrins to the extracellular
      matrix. Recent studies have shown that Src, through its SH2 domain, stably
      associates with pp125FAK and that this association prevents dephosphorylation of
      pp125FAK in vitro by protein tyrosine phosphatases. In this report, we identify
      Tyr-397 as the primary in vivo and in vitro site of p125FAK tyrosine
      phosphorylation and association with Src. Substituting phenylalanine for tyrosine
      at position 397 significantly reduces p125FAK tyrosine phosphorylation and
      association with Src but does not abolish p125FAK kinase activity. In addition,
      p125FAK kinase is able to trans-phosphorylate Tyr-397 in vitro in a kinase
      deficient p125FAK variant. Phosphorylation of Tyr-397 provides a site [Y(P)AEI]
      that fits the consensus sequence for the binding of Src.

PMID- 7739565
TI  - Functional interaction of c-Ets-1 and GHF-1/Pit-1 mediates Ras activation of
      pituitary-specific gene expression: mapping of the essential c-Ets-1 domain.
AB  - The mechanism by which activation of common signal transduction pathways can
      elicit cell-specific responses remains an important question in biology. To
      elucidate the molecular mechanism by which the Ras signaling pathway activates a
      cell-type-specific gene, we have used the pituitary-specific rat prolactin (rPRL)
      promoter as a target of oncogenic Ras and Raf in GH4 rat pituitary cells. Here we
      show that expression of either c-Ets-1 or the POU homeo-domain transcription
      factor GHF-1/Pit-1 enhance the Ras/Raf activation of the rPRL promoter and that
      coexpression of the two transcription factors results in an even greater
      synergistic Ras response. By contrast, the related GHF-1-dependent rat growth
      hormone promoter fails to respond to Ras or Raf, indicating that GHF-1 alone is
      insufficient to mediate the Ras/Raf effect. Using amino-terminal truncations of c
      Ets-1, we have mapped the c-Ets-1 region required to mediate the optimal Ras
      response to a 40-amino-acid segment which contains a putative mitogen-activated
      protein kinase site. Finally, dominant-negative Ets and GHF constructs block Ras
      activation of the rPRL promoter, and each blocks the synergistic activation
      mediated by the other partner protein, further corroborating that a functional
      interaction between c-Ets-1 and GHF-1 is required for an optimal Ras response.
      Thus, the functional interaction of a pituitary-specific transcription factor,
      GHF-1, with a widely expressed nuclear proto-oncogene product, c-Ets-1, provides
      one important molecular mechanism by which the general Ras signaling cascade can
      be interpreted in a cell-type-specific manner.

PMID- 7739566
TI  - DNA-binding and transactivation properties of Pax-6: three amino acids in the
      paired domain are responsible for the different sequence recognition of Pax-6 and
      BSAP (Pax-5).
AB  - Pax-6 is known to be a key regulator of vertebrate eye development. We have now
      isolated cDNA for an invertebrate Pax-6 protein from sea urchin embryos.
      Transcripts of this gene first appear during development at the gastrula stage
      and are later expressed at high levels in the tube foot of the adult sea urchin.
      The sea urchin Pax-6 protein is highly homologous throughout the whole protein to
      its vertebrate counterpart with the paired domain and homeodomain being virtually
      identical. Consequently, we found that the DNA-binding and transactivation
      properties of the sea urchin and mouse Pax-6 proteins are very similar, if not
      identical. A potent activation domain capable of stimulating transcription from
      proximal promoter and distal enhancer positions was localized within the C
      terminal sequences of both the sea urchin and mouse Pax-6 proteins. The
      homeodomain of Pax-6 was shown to cooperatively dimerize on DNA sequences
      consisting of an inverted repeat of the TAAT motif with a preferred spacing of 3
      nucleotides. The consensus recognition sequence of the Pax-6 paired domain
      deviates primarily only at one position from that of BSAP (Pax-5), and yet the
      two proteins exhibit largely different binding specificities for individual,
      naturally occurring sites. By creating Pax-6-BSAP fusion proteins, we were able
      to identify a short amino acid stretch in the N-terminal part of the paired
      domain which is responsible for these differences in DNA-binding specificity.
      Mutation of three Pax-6-specific residues in this region (at positions 42, 44,
      and 47 of the paired domain) to the corresponding amino acids of BSAP resulted in
      a complete switch of the DNA-binding specificity from Pax-6 to BSAP. These three
      amino acids were furthermore shown to discriminate between the Pax-6- and BSAP
      specific nucleotide at the divergent position of the two consensus recognition
      sequences.

PMID- 7739564
TI  - GAL4 interacts with TATA-binding protein and coactivators.
AB  - A major goal in understanding eukaryotic gene regulation is to identify the
      target(s) of transcriptional activators. Efforts to date have pointed to various
      candidates. Here we show that a 34-amino-acid peptide from the carboxy terminus
      of GAL4 is a strong activation domain (AD) and retains at least four proteins
      from a crude extract: the negative regulator GAL80, the TATA-binding protein
      (TBP), and the putative coactivators SUG1 and ADA2. TFIIB was not retained.
      Concentrating on TBP, we demonstrate in in vitro binding assays that its
      interaction with the AD is specific, direct, and salt stable up to at least 1.6 M
      NaCl. The effects of mutations in the GAL4 AD on transcriptional activation in
      vivo correlate with their affinities to TBP. A point mutation (L114K) in yeast
      TBP, which has been shown to compromise the mutant protein in both binding to the
      VP16 AD domain and activated transcription in vitro, reduces the affinity to the
      GAL4 AD to the same degree as to the VP16 AD. This suggests that these two
      prototypic activators make similar contacts with TBP.

PMID- 7739568
TI  - The G1/S boundary-specific enhancer of the rat cdc2 promoter.
AB  - Multiple species of G1 cyclins and cyclin-dependent kinases are induced
      sequentially during G1 phase, and the expression of cyclin A and cdc2 genes is
      subsequently induced at the G1/S boundary. To analyze the mechanism of cdc2
      promoter activation, the 5'-flanking region of the rat cdc2 gene was isolated and
      its structural features were characterized. The highly conserved sequence between
      human and rat cdc2 genes is present in the basal promoter region from positions 
      183 to -122, which contains the E box, SpI, and E2F motifs. The expression of 5'
      sequential deletion derivatives of the promoter fused to luciferase cDNA in rat
      3Y1 cells revealed the presence of the enhancer element. The presumed enhancer
      region was further analyzed by the introduction of base substitutions and by the
      formation of DNA-protein complexes with cell extracts prepared at various times
      during the G1-to-S-phase progression. These analyses revealed that the enhancer
      sequence, AAGTTACAAATA, located from -276 to -265, confers strong inducibility on
      the basal promoter at the G1/S boundary. The base substitutions introduced into
      the motifs of transcription factors indicated that the E2F motif is essential for
      the enhancer-dependent activation of the cdc2 promoter at the G1/S boundary.
      Electrophoretic mobility shift assays and DNase I footprinting showed that a
      factor which interacts with the enhancer element is induced late in G1 phase.

PMID- 7739567
TI  - In vitro analysis of mutations causing myoclonus epilepsy with ragged-red fibers
      in the mitochondrial tRNA(Lys)gene: two genotypes produce similar phenotypes.
AB  - Cytoplasts from patients with myoclonus epilepsy with ragged-red fibers harboring
      a pathogenic point mutation at either nucleotide 8344 or 8356 in the human
      mitochondrial tRNA(Lys) gene were fused with human cells lacking endogenous
      mitochondrial DNA (mtDNA). For each mutation, cytoplasmic hybrid (cybrid) cell
      lines containing 0 or 100% mutated mtDNAs were isolated and their genetic,
      biochemical, and morphological characteristics were examined. Both mutations
      resulted in the same biochemical and molecular genetic phenotypes. Specifically,
      cybrids containing 100% mutated mtDNAs, but not those containing the
      corresponding wild-type mtDNAs, exhibited severe defects in respiratory chain
      activity, in the rates of protein synthesis, and in the steady-state levels of
      mitochondrial translation products. In addition, aberrant mitochondrial
      translation products were detected with both mutations. No significant
      alterations were observed in the processing of polycistronic RNA precursor
      transcripts derived from the region containing the tRNA(Lys) gene. These results
      demonstrate that two different mtDNA mutations in tRNA(Lys), both associated with
      the same mitochondrial disorder, result in fundamentally identical defects at the
      cellular level and strongly suggest that specific protein synthesis abnormalities
      contribute to the pathogenesis of myoclonus epilepsy with ragged-red fibers.

PMID- 7739570
TI  - Differential regulation of accessory mitogenic signaling receptors by the T cell
      antigen receptor.
AB  - In addition to the antigen receptor, resting T cells express a number of
      receptors that can be stimulated to generate proliferative signals. These
      "accessory" receptors require co-expression of the T cell receptor (TCR),
      suggesting that they channel their signals via secondary activation of the signal
      transduction function of the CD3-TCR complex. Little is known about how different
      receptors control each other's function when one or more stimuli are presented at
      the same time. In order to study the regulation of accessory receptors by the CD3
      TCR and vice versa, we have investigated the activation of the CD2 cell adhesion
      molecule receptor and the pertussis toxin receptor, a 43 kDa plasma membrane
      protein. Both receptors can activate signal transduction pathways in T cells
      similar to that of the CD3-TCR, including increases in Ca2+ and
      phosphatidylinositol turnover. They are also similar in that they utilize the
      antigen receptor to transmit their signals to the cell since CD3-TCR(-) mutants
      cannot be activated via either CD2 or the toxin receptor. We have previously
      shown that submaximal stimulation of the CD3-TCR blocks second messenger
      generation and proliferation in response to pertussis toxin. This heterologous
      desensitization was unidirectional since activation of the toxin receptor had no
      effect on CD3-TCR function. Here we extend these studies to show that activation
      of both CD2 and the toxin receptor led to rapid tyrosine phosphorylation of three
      similar proteins. Submaximal stimulation of the CD3-TCR completely inhibited
      toxin receptor-stimulated tyrosine protein kinase activity but did not
      desensitize CD2 function as determined by activation of tyrosine protein
      phosphorylation. Furthermore, CD2 stimulation did not lead to desensitization of
      the pertussis toxin receptor. These data support a system of complex regulatory
      relationships between different signaling receptors and suggest a model for
      signal integration and inter-receptor cross-talk in T cell activation.

PMID- 7739571
TI  - Engineered idiotypes. Immunochemical analysis of antigenized antibodies
      expressing a conformationally constrained Arg-Gly-Asp motif.
AB  - We report on the immunochemical characterization of two antibodies engineered to
      express RGD, a peptide from adhesive proteins of the extracellular matrix. One or
      three RGD motifs were introduced in the third complementarity-determining region
      (CDR) of a murine heavy (H) chain variable (V) region gene yielding two
      antibodies, gamma 1RGD and gamma 1(RGD)3. A murine monoclonal antibody (mAb)
      raised against an RGD-containing synthetic peptide bound in Western blot the H
      chain of both gamma 1RGD and gamma 1(RGD)3. Pronectin F, a genetically-engineered
      polymer containing RGD, abrogated this binding. Anti-idiotypic antibodies against
      the (RGD)3 loop were generated in a rabbit by immunization with gamma 1(RGD)3.
      Anti-idiotype antibodies purified by affinity-chromatography on the synthetic
      peptide GRGDSPC reacted in ELISA with gamma 1(RGD)3 and human fibronectin.
      Adhesive proteins, unlike RGD-containing synthetic peptides, were able to
      interfere with the interaction between gamma 1(RGD)3 and the anti-idiotypic
      antibodies. These results suggest that it is possible to genetically engineer the
      hypervariable loops of immunoglobulins and confer them new idiotypic
      characteristics. These results support the concept of antibody mimicry.

PMID- 7739572
TI  - Pattern of usage of the VH4-21 gene by B lymphocytes in a patient with EBV
      infection indicates ongoing mutation and class switching.
AB  - Following infection with EBV, patients have selectively raised serum levels of
      immunoglobulins encoded by the VH4-21 gene. In order to follow the detailed
      pattern of usage of the VH4-21 gene by blood B lymphocytes of a typical patient
      during infection, EBV lines were established, and transformed B cells were
      hybridized and cloned. In addition, to widen the genetic analysis, cDNA
      preparations from the EBV transformants using the gene were also analysed by
      polymerase chain reaction, cloning and sequencing. The majority (12/15) of the
      clonally distinct sequences derived from IgM utilized the VH4-21 gene in germ
      line configuration; however, 3/15 showed replacement mutations. For one of these,
      a heterogeneous pattern of mutation within the clone indicated ongoing mutation,
      and one sequence contained a stop codon. Three distinct clones which had
      rearranged to C gamma were obtained, and all were extensively mutated, with some
      evidence for a role for antigen in selection. Following resolution of the
      infection, no VH4-21-encoded products were detectable by this approach. It
      appears therefore that infection with EBV leads to selective activation, mutation
      and class switching of the VH4-21 gene, with the unusual feature that B cells
      harbouring deleterious mutations in the functional gene are able to survive in
      the circulation.

PMID- 7739569
TI  - Initiation of latent DNA replication in the Epstein-Barr virus genome can occur
      at sites other than the genetically defined origin.
AB  - Our laboratory has previously shown that replication of a small plasmid, p174,
      containing the genetically defined Epstein-Barr virus (EBV) latent origin of
      replication, oriP, initiates within oriP at or near a dyad symmetry (DS) element
      and terminates specifically at a family of repeated sequences (FR), also located
      within oriP. We describe here an analysis of the replication of intact
      approximately 170-kb EBV genomes in four latently infected cell lines that uses
      two-dimensional gel replicon mapping. Initiation was detected at oriP in all EBV
      genomes examined; however, some replication forks appear to originate from
      alternative initiation sites. In addition, pausing of replication forks was
      observed at the two clusters of EBV nuclear antigen 1 binding sites within oriP
      and at or near two highly expressed viral genes 0.5 to 1 kb upstream of oriP, the
      EBV-encoded RNA (EBER) genes. In the Raji EBV genome, the relative abundance of
      these stalled forks and the direction in which they are stalled indicate that
      most replication forks originate upstream of oriP. We thus searched for
      additional initiation sites in the Raji EBV and found that the majority of
      initiation events were distributed over a broad region to the left of oriP. This
      delocalized pattern of initiation resembles initiation of replication in several
      well-characterized mammalian chromosomal loci and is the first described for any
      viral genome. EBV thus provides a unique model system with which to investigate
      factors influencing the selection of replication initiation and termination sites
      in mammalian cells.

PMID- 7739573
TI  - Human factor H and C4b-binding protein serve as factor I-cofactors both
      encompassing inactivation of C3b and C4b.
AB  - Human factor H in the complement (C) system has been characterized as a decay
      accelerator for the alternative C pathway C3 convertase and a cofactor for factor
      I-mediated inactivation of C3b. The current concept is that it does not serve as
      a C4b-inactivating cofactor. In the present study, we demonstrated that in fluid
      phase, factor H and Factor I can cleave methylamine-treated C4(C4ma), a C4b
      analogue, to C4d, regardless of its isotype. The buffer pH and ionic strength
      were critical factors for the C4ma cleavage, which proceeded at around pH 6.0 and
      low conductivity around 3.0 mS. Similar results were obtained with fluid-phase
      C4b. Cell-bound C4b, however, did not undergo factor I-mediated inactivation by
      factor H. Hence, all of the human cofactors reported to date can mediate factor I
      mediated cleavage of both C3b and C4b at least in the fluid-phase.

PMID- 7739574
TI  - The leukocyte integrin gene CD11c is transcriptionally regulated during monocyte
      differentiation.
AB  - The leukocyte integrins, LFA-1, Mac-1 and p150,95, are heterodimeric proteins
      that consist of a distinct alpha and a common beta subunit. The beta subunit gene
      (CD18) is constitutively expressed on all leukocytes, however, the alpha subunit
      genes for LFA-1, Mac-1 and p150,95 (CD11a, CD11b and CD11c, respectively) show
      cell- and developmental stage-specific expression. We investigated the regulation
      of the CD11c gene in the promyeloblastic leukemic cell line, HL60, following
      differentiation along the monocytic pathway with phorbol 12-myristate 13-acetate
      (PMA). The steady-state level of CD11c mRNA increased markedly over 48 hr from
      the undetectable level present before differentiation. The half-life of CD11c
      MRNA in differentiated HL60 cells was not unusually long and similar to that of
      CD18 mRNA found in both undifferentiated and differentiated cells which suggested
      that altered mRNA stability did not account for the appearance of CD11c mRNA.
      Nuclear run-on analysis revealed that transcriptional activation during
      differentiation resulted in the appearance of CD11c mRNA. Inhibition of protein
      synthesis by cycloheximide in undifferentiated HL60 cells did not result in
      transcriptional activation of the CD11c gene. However, there was a significant
      increase (approximately eight-fold) in the steady-state level of CD18 mRNA which
      was not the result of transcriptional activation. Inhibition of protein synthesis
      in differentiated HL60 cells did not lead to significant changes in the steady
      state levels of either CD11c or CD18 mRNAs. These findings indicated that the
      CD11c gene is regulated by transcriptional mechanisms which require prior protein
      synthesis. Transcriptional activation of the CD18 gene as a result of
      differentiation with PMA also requires protein synthesis. Further, in the absence
      of protein synthesis in undifferentiated HL60 cells, post-transcriptional
      mechanisms stabilize CD18 mRNA.

PMID- 7739575
TI  - HIV-1 rsgp41 depends on calcium for binding of human c1q but not for binding of
      gp120.
AB  - Human immunodeficiency virus type 1 activates the complement cascade via the
      classical pathway by direct binding of C1q through specific sites in the TM
      surface protein, gp41. In this paper we investigated the divalent cation
      dependence of the interaction between HIV-1 gp41 and C1q or gp120. A solid phase
      radioimmunoassay was used to investigate the interaction between a recombinant
      soluble form of HIV-1 gp41 (rsgp41) and C1q and an enzyme linked immunoassay was
      used to investigate the interaction between rsgp41 and gp120. The interaction
      between C1q and rsgp41, but not between C1q and immune complexes, was dependent
      upon the presence of calcium. Calcium could not be replaced by larger cations
      such as strontium, barium, lead or smaller ions such as magnesium and manganese.
      Zinc increased binding to 22% of binding achieved with calcium. The interaction
      between rsgp41 and gp120 was not dependent upon the presence of divalent ions.
      Thus, calcium is required for the interaction between rsgp41 and C1q, whereas the
      interaction between rsgp41 and gp120 is independent of divalent cations.

PMID- 7739576
TI  - Temperature-dependent binding of IgG1 to a human high affinity Fc receptor.
AB  - We have measured the kinetics of binding and unbinding of human IgG1 to a human
      high affinity Fc receptor (FcgammaI) at several temperatures. The association
      rate constant (kappaf) and the dissociation rate (kr) of this complex was
      determined with 125I-IgG1 monomer and FcgammaI on U937 cells. At 37 degrees C,
      kappaf = 2.7 x 10(5) M(-1) s(-1) and kappar = 4.5 x 10(-4) s(-1). Both rates
      decreased with decreasing temperature. However, the equilibrium association
      constant, Ka, increased with decreasing temperature. From the temperature
      dependence of Ka we determined that the binding of IgF1 to FcgammaI is driven
      largely by enthalpic forces and that a small but positive entropic contribution
      to free energy leads to a tighter complex at lower temperature.

PMID- 7739577
TI  - Processing of human factor I in COS-1 cells co-transfected with factor I and
      paired basic amino acid cleaving enzyme (PACE) cDNA.
AB  - Factor I is an active serine proteinase in plasma that regulates both the
      classical and alternative complement pathways by cleaving C3b and C4b thereby
      preventing the assembly of C3 and C5 convertase enzymes. In this study, a full
      length human factor I cDNA was cloned into the pMT2 expression vector and the
      pMT2-fI construct was expressed transiently in COS-1 cells and stably in CHO-K1
      cells. The transfected COS-1 cells secreted large amounts of recombinant pro
      factor I (85 kD). Co-transfection of COS-1 cells with pMT2-fI and the cDNA
      expression plasmid for PACE (paired basic amino acid cleaving enzyme), resulted
      predominantly in the secretion of a proteolytically processed form of recombinant
      factor I (heavy chain, 47 kD; light chain, 35 kD). Following co-transfection of
      pMT2-fI and pSVNeo.1 into CHO-K1 cells and selection in medium containing G418, a
      stably transfected clone was isolated that secreted pro-factor I (85 kd) and
      proteolytically processed factor I (heavy chain, 48 kD; light chain, 37 kD) in
      approximately equal amounts. The molecular sizes of the subunit chains of the
      expressed factor I were generally slightly smaller than those of human plasma
      factor I. The activity of recombinant factor I present in the culture
      supernatants of transfected COS-1 and CHO-K1 cells was assayed by its ability to
      cleave 125I-C3b in the presence of factor H and was found to be low when compared
      with factor I purified from human plasma. However, since the functional activity
      of purified factor I was reduced approximately 50% in the presence of conditioned
      medium from non-transfected cells, it is suggested that the cold C3b present in
      the factor I-deficient serum used to supplement the culture medium probably
      competed with the 125I-C3b tracer, thereby decreasing the sensitivity of the
      assay for the recombinant factor I proteins.

PMID- 7739578
TI  - Endoscopy of the upper respiratory and upper gastrointestinal tract.

PMID- 7739579
TI  - Preparation for intubation of the awake patient.

PMID- 7739580
TI  - Use of the flexible fiberoptic laryngoscope.
AB  - The flexible fiberoptic laryngoscope is an excellent instrument for performing
      tracheal intubation in patients with abnormal upper airway anatomy. In order to
      prepare to use the fiberscope for the infrequent patient with a "difficult"
      airway, the anesthesiologist must initially learn and practice the technique in
      patients with normal anatomy. Orotracheal intubation with the fiberscope in these
      patients receiving general anesthesia provides the anesthesiologist with abundant
      opportunities to become skillful.

PMID- 7739581
TI  - The unanticipated difficult intubation with adequate mask ventilation.

PMID- 7739582
TI  - The physics of fiberoptic endoscopy.

PMID- 7739583
TI  - Predictable problems with flexible fiberoptic laryngoscopy.

PMID- 7739584
TI  - Flexible fiberoptic bronchoscopy: a practical guide to examining infants and
      children.

PMID- 7739585
TI  - Learning fiberoptic-guided endotracheal intubation.

PMID- 7739587
TI  - Upper gastrointestinal endoscopy.
AB  - Upper intestinal endoscopy is a well-accepted method for evaluation of the
      esophagus, stomach, and duodenum. The techniques are standardized and extremely
      safe. The therapeutic capability for control of gastrointestinal hemorrhage is a
      major advance in the treatment of gastrointestinal bleeding. Endoscopic
      ultrasound is useful in the staging of upper intestinal malignancies. Above all,
      the ability to directly visualize the mucosal lining, to obtain biopsies, and to
      remove polyps has made endoscopy a primary tool for investigation of upper
      gastrointestinal pathology.

PMID- 7739586
TI  - Fiberoptics in otolaryngology.

PMID- 7739588
TI  - Case 1-1994. From the Weekly Grand Rounds of the Department of Dermatology at the
      Mount Sinai Hospital.

PMID- 7739589
TI  - Hepatic hydatid disease in Iran, with review of the literature.
AB  - We retrospectively reviewed 126 surgically proven cases of hydatid cyst of the
      liver selected from medical records of patients diagnosed clinically over the
      eight-year period 1972 to 1980. Sixty percent of the patients were in the third
      and fourth decades of life. The most common initial complaint was either right
      upper abdominal pain or a sensation of fullness, generally for more than two
      months. One or more cysts were more apt to be in the right lobe, and were subject
      to infection, rupture, or fistula formation. In 6% of patients, other
      intraabdominal cysts were found during surgery. In a few patients, the plain
      abdominal radiographs revealed curvilinear calcification. Upper gastrointestinal
      barium studies showed extrinsic pressure on the stomach or duodenum. Chest
      radiographs occasionally showed elevated right hemidiaphragm, right lower lobe
      infiltrate/atelectasis, right pleural effusion, and a pulmonary hydatid cyst.
      Liver-spleen scintigraphy often revealed a space-occupying lesion, but there were
      discrepancies either in number or location of cysts when compared with the
      surgical findings. All angiographic results were abnormal. Patients with infected
      cysts differed from the rest by a more common history of fever, and a greater
      incidence of right pleural effusion on chest x-ray. Literature on
      pathophysiology, radiologic findings (including CT scan and ultrasonography), and
      surgical and medical therapy of hydatid disease of the liver is reviewed.

PMID- 7739590
TI  - Hepatic hydatid disease: current surgical treatment.
AB  - In the 11 years 1980 through 1990, we performed a total of 273 operations for
      hydatid disease of the liver in 252 patients, including 35 patients who were over
      the age of 75 years. Cysts were multiple in 24.6%, calcified in 17.9%, and
      ruptured to adjacent viscera in 12.3% of cases. Ruptured cysts were small as well
      as large. Coexisting gallstone disease was found in 14.3% of cases. Reoperations
      for recurrence were performed in 6.4% of cases. We believe that once the
      diagnosis is made, the treatment should be surgical, without regard to cyst size,
      the age of the patient, or the presence or absence of symptoms. Total
      pericystectomy, which eradicates the parasitic disease and thus minimizes the
      risk of recurrence, is the procedure of choice (17.3% in this series). When total
      pericystectomy is not feasible and the cysts are large and deeply placed,
      subtotal pericystectomy, in which only a small piece of the cystic wall is
      preserved, is a successful alternative (12.5% in this series). For complicated
      cysts, external drainage of the cystic cavity is necessary despite the known
      morbidity this procedure entails. In patients in this series undergoing external
      drainage, infection of the residual cavity and postoperative biliary fistula were
      the main causes of morbidity.

PMID- 7739591
TI  - [Level of sodium and potassium in Streptomyces chrysomallus subsp. macrotetrolidi
      cells--producers of macrotetralide antibiotics].
AB  - The ionophoretic macrotetrolide antibiotics selective to monovalent cations K+
      and mainly to NH4+ were determined during the lag period of culture growth. At
      this stage the cells contain the maximal amounts of Na+ and K+. Macrotetrolides,
      whose selectivity to Na+ and K+ varies, can regulate the intracellular content of
      these cations by participating in the cation transport. The authors propose that
      the cells possess furosemide sensitivity and K+/Na+ ATPase transport systems.

PMID- 7739592
TI  - [Expression of pectate lyase genes of Erwinia carotovora subsp. carotovora 17A
      and Erwinia carotovora subsp. atroseptica 36A in Erwinia carotovor substp.
      atroseptica 36A cells].
AB  - E.atroseptica 36A cells were transformed by the recombinant plasmids p27-1 and
      pEA364 (derivatives of the vector plasmid pUC19) containing pectate lyase genes
      of E.carotovora 17A and E.atroseptica 36A, respectively. The synthesis of pectate
      lyases determined by the cloned genes of bacteria of both subspecies, as well as
      the synthesis of the native enzymes, were induced by sodium poly pectate.
      Increase of the dose of pectate lyase genes did not result in alteration of
      pectate lyase secretion by E.atroseptica 36ApEA364 cells. At the same time, the
      efficiency of secretion of heterologous pectate lyases by E.atroseptica 36Ap27-1
      cells was lower. The synthesis and secretion of the resident isoenzymes are as
      efficient as those of the parental cells. The results indicate a high specificity
      of the pectinase secretory system in Erwinia of different species and, moreover,
      subspecies.

PMID- 7739593
TI  - [Use of a DNA-DNA hybridization method for studying Corynebacterium diphtheriae
      strains].
AB  - In addition to traditional tests, a battery of DNA probes was used to
      characterize 134 toxigenic and 125 nontoxigenic C.diphtheriae strains isolated in
      Russia in 1986-1989. 2.5% of nontoxigenic strains carried the determinants of
      both toxin subunits A and B, and 20% possessed at least a fragment of the gene
      determining toxin synthesis. Optimal conditions of hybridization technology were
      found. The method may be used as an alternative to traditional techniques in
      diagnostic studies and screenings.

PMID- 7739594
TI  - Studies of Rickettsia prowazekii antigens in immunoblotting with specific sera of
      infected white mice.
AB  - Five strains of Rickettsia prowazekii different in origin, biological and genetic
      properties were compared in protein and LPS patterns by the polyacrylamide gel
      electrophoresis and in antigenic properties by immunoblotting with specific sera
      of infected white mice. Three virulent strains Breinl, G and Katsinjan had
      identical protein patterns and differed from isogenic pair of strains E and EVir
      in the electrophoretic properties of 29-30 kDa proteins. Silver-strained LPS
      patterns were different in five compared strains. Strain G and strain Katsinjan
      had the longest O-chaines of LPS. Polyclonal mouse antisera contained specific
      antibodies which mainly directed against LPS and 25-60 kDa proteins. Strains E
      and EVir were identical in all performed immunoblotting reactions and separated
      from three virulent strains. Out of virulent strains, whole cell antigen of
      strain Katsinjan and LPS antigen of strain G had different reactions in
      comparison with correspondent antigen of the standard strain Breinl.

PMID- 7739595
TI  - [Cloning and expression of the phosphatidylinositol-specific phospholipase C gene
      from Listeria monocytogenes].
AB  - The gene for phosphatidylinositol-specific phospholipase C (PI-PLC) of Listeria
      monocytogenes has been cloned and shown to be expressed in Escherichia coli cells
      from own as well as from the lactose gene promoter. The recombinant plasmid has
      been constructed on the basis of pRIT2T vector and carries the hybrid gone. 3-end
      of which is a fragment of protein A gene of Staphylococcus aureus. 3-end is a
      gene for phospholipase plcA, both in the same reading frame. The resultant
      construction is shown to code in Escherichia coli cells for the hybrid
      recombinant protein A:Pl-PLC. Purified preparation of the hybrid protein and
      polyclonal rabbit antiserum to it were obtained. The obtained antiserum to the
      hybrid protein containing phospholipase as en C-end domain has been shown to
      react specifically to phospholipase in Escherichia coli recombinant strain
      harbouring the constructed recombinant plasmid as well as the one in the culture
      fluid of listeria.

PMID- 7739596
TI  - [Study of lectin-binding segments on the surface of Leishmania gymnoductyli
      reptulii during in vitro differentiation].
AB  - Changes in expression of lectin-binding sites, which are complex carbohydrate
      structures of Leishmania gymnoductyli reptulii, were studied by the classical
      lectin agglutination test. The results evidence that this test may be used to
      assess the level of ontogenesis of Leishmania strains, as well as for the
      detection and isolation of metacyclic (invasion) stage from Leishmania cell
      culture by lectins.

PMID- 7739597
TI  - [In vitro and in vivo study of the activity of secreted alkaline phosphatase mRNA
      ribozyme gene].
AB  - A ribozyme was constructed of the catalytic domain of tobacco ringspot virus
      satellite RNA and flanking sequences complementary to the target, secreted
      alkaline phosphatase (SEAP) mRNA. The ribozyme specifically cleaved the substrate
      in vitro; compared with that constant temperature. The relationship between
      specific endoribonuclease activity of the ribozyme and Mg2+ concentration was
      shown. The ribozyme was active in 293 cell line which was cotransfected with
      plasmids carrying the SEAP gene under control of RSV LTR promoter and the
      ribozyme gene under early HCMV promoter: SEAP activity reduced by half.

PMID- 7739598
TI  - Learning rules to predict rodent carcinogenicity of non-genotoxic chemicals.
AB  - The results of short-term assays (induction of chromosomal aberrations and sister
      chromatid exchanges, oncogenic transformations and cellular toxicity) together
      with MTD (maximum tolerated dose) values and physical chemical properties of non
      genotoxic (i.e. Salmonella non-mutagens) carcinogens and non-carcinogens were
      submitted to RL, an inductive learning program. RL was able to learn rules that
      correctly predicted between 70 and 80% of non-genotoxic chemicals. This is a
      marked improvement over current predictions using only the results of short-term
      assays and exceeds the predictions of human experts that used the whole spectrum
      of acute and subchronic toxicity results as well as human knowledge and
      intuition.

PMID- 7739599
TI  - Efficient induction of chromosome-type aberrations by topoisomerase II inhibitors
      closely associated with stabilization of the cleavable complex in cultured
      fibroblastic cells.
AB  - Eukaryotic topoisomerase II (Topo-II) inhibitors such as etoposide, adriamycin
      and mitoxantrone, which commonly stabilize the cleavable complex of the enzyme
      and DNA, have been found to efficiently induce chromosome-type aberrations
      (mainly breaks and exchanges) in cultured Chinese hamster lung fibroblastic cells
      (CHL cells). To clarify whether the induction of chromosome-type aberrations is
      mediated by stabilization of the cleavable complex, the present study
      investigated (1) the correlation between the induction of chromosome-type
      aberrations and the amount of cleavable complex formed; and (2) the ATP
      dependence of the Topo-II inhibitor-induced chromosome-type aberrations due to
      the ATP requirement of cleavable complex formation by Topo-II. First, in cells
      treated with the Topo-II inhibitors, (etoposide, adriamycin) and aclarubicin, an
      antagonist of the inhibitor of cleavable complex formation, the frequency of
      chromosome-type aberrations decreased dose-dependently with aclarubicin, in
      contrast to an increase of chromatid-type aberrations. The formation of the
      cleavable complex was further established by a proteinase K/SDS precipitation
      assay for cleaved double-strand DNA in a cell-free system and in CHL cells.
      Results from both experiments showed that aclarubicin caused a dose-dependent
      suppression of the accumulation of the cleavable complex induced by etoposide,
      which corresponded particularly well to the reduction of chromosome-type
      aberrations in etoposide-treated cells. In ATP-depleted cells simultaneously
      treated with etoposide and dinitrophenol (DNP), chromosome-type aberrations were
      reduced as compared with DNP-untreated cells, in contrast to an increase of
      chromatid exchanges in the cells. This means that etoposide-induced chromosome
      type aberrations in ATP-depleted cells may be attributable to incompleteness of
      Topo-II activities to form DNA double-strand breaks. The present findings
      indicate that the stabilization of the cleavable complex on Topo-II is closely
      associated with the induction of chromosome-type aberrations.

PMID- 7739600
TI  - Molecular analysis of four ENU induced triosephosphate isomerase null mutants in
      Mus musculus.
AB  - Four ENU-induced mutations were previously identified at the triosephosphate
      isomerase (TPI) locus in mouse germinal mutation experiments. Each of the mutants
      is associated with a 50% loss of enzymatic activity in the F1 (heterozygous)
      animals. Exons of the TPI gene from control mice and heterozygous mutant mice
      were PCR amplified and sequenced as necessary to determine the molecular lesion
      in the mutant alleles. Mutants Tpi*M-1NEU and Tpi*M-2NEU carried the same T:A to
      A:T transversion in exon 6, resulting in a Leu to Gln substitution at residue
      192. Amino acid residue 192 is located in alpha-helix H6 of the protein. Tpi*M
      4NEU contained a T:A to A:T transversion within the codon for residue 162 in exon
      5, also causing a Leu to Gln substitution. This mutation is located at the
      beginning of beta-strand B6, within a highly conserved sequence region
      surrounding the active site residue Glu 165. Sequence analysis of Tpi*M-3NEU
      revealed an A:T to C:G transversion, changing the stop codon to a codon for Cys,
      with the resulting addition of 19 predominantly hydrophobic amino acids to the
      protein. All four mutations occurred at an A:T base pair. In each case, the
      mutation site was flanked on both sides by G:C base pairs. Each of the sequence
      alterations has a potential impact on the structure of the TPI protein that is
      consistent with the existence of a null allele. In addition to providing insight
      into the molecular basis of ENU induced germ cell mutations and the differences
      in mutation spectra among organisms, these mutants represent models for structure
      function studies of this highly conserved enzyme.

PMID- 7739601
TI  - UV-light induces delayed mutations in Chinese hamster cells.
AB  - The possibility was examined that mutational events at the glucose 6-phosphate
      dehydrogenase locus can be delayed for significantly more than one or two cell
      divisions following treatment of Chinese hamster cells with UV light. To detect
      these later mutant events, the proportion of G6PD-mutant cells in a colony was
      obtained by replating cells from a single colony 5-7 days after UV irradiation
      and staining the resulting colonies for G6PD activity. Eight colonies out of a
      total of 1657 colonies from the treated population yielded G6PD-negative colonies
      upon replating, while no mutant clones were obtained from 947 colonies grown from
      untreated cells. One clone contained only mutant cells suggesting that the
      mutation occurred before the first cell division after irradiation. A second
      clone contained a 1:1 ratio of mutant to wild-type cells suggesting that the
      mutation occurred at the first cell division. The remaining six clones contained
      low numbers of mutant cells and the ratio of mutant to wild-type cells in these
      clones was in agreement with the theoretical ratios expected for mutations
      occurring at the fourth (1:13), sixth (1:63), seventh (1:127), eighth (1:255),
      ninth (1:511), and eleventh (1:2047) cell division after UV light exposure. G6PD
      mutant cells deficient in staining activity were isolated from five clones and
      all have significant reductions in G6PD activity confirming the genetically
      stable character of these mutants. These results support the conclusion that UV
      light induces mutants for up to 11 cell generations after treatment of mammalian
      cells and suggest that mutagens can induce in mammalian DNA long-term alterations
      which act to increase the apparently spontaneous mutation frequency.

PMID- 7739602
TI  - Structure-activity relationships of anthraquinones as inhibitors of 7
      ethoxycoumarin O-deethylase and mutagenicity of 2-amino-3-methylimidazo[4,5
      f]quinoline.
AB  - The antimutagenicity of 17 natural and synthetic anthraquinones was determined
      using Salmonella typhimurium TA98 against 2-amino-3-methylimidazo[4,5-f]quinoline
      (IQ) in the presence of Aroclor 1254-induced rat hepatic S9. In general, the
      relationship between the chemical structures of anthraquinones and their
      antimutagenicity was found to contain one or more of the following features: (i)
      C9 carbonyl group, (ii) hydroxyl group at C1 and C4, (iii) C2 ethyl group, and
      (iv) C3 methyl group. The inhibitory effect of anthraquinones on 7-ethoxycoumarin
      O-deethylase (ECD) of Aroclor, 1254-induced hepatic microsomes was also examined.
      In addition, we studied the effect of anthraquinones on the metabolism of IQ by
      Aroclor 1254-induced microsomes using high-performance liquid chromatography. The
      antimutagenicity correlated with the inhibition of cytochrome P-450IA2-linked ECD
      activity in hepatic microsomes, and with the inhibition of N-hydroxy-IQ formation
      of IQ metabolism by hepatic microsomes. Moreover, we also examined the
      antimutagenicity of anthraquinones against synthetic N-hydroxy-IQ. Quinizarin and
      anthraflavic acid were shown to have more effect on the direct mutagenicity of N
      hydroxy-IQ than that of the anthraquinones tested. This might explain why both
      anthraquinones showed higher antimutagenicity; although they inhibited ECD less.
      These results suggest that there exist at least two mechanisms of action in
      modifying roles of anthraquinones on the mutagenicity of IQ: (i) mediation
      through interaction with microsomal activating enzymes to inhibit the major
      active metabolite of N-hydroxy-IQ formation and (ii) direct interaction with the
      proximate metabolite of IQ, N-hydroxy-IQ, to block its attack on DNA.

PMID- 7739604
TI  - The genotoxicity of benzanthracenes: a quantitative structure-activity study.
AB  - Molecular orbital (MO) evaluations of a series of 14 methyl-substituted
      benz[alpha]anthracenes, calculated by the complete neglect of differential
      overlap (CNDO/2) method, are reported. By quantitative structure-activity
      relationship (QSAR) analysis, the carcinogenic and mutagenic potencies of these
      compounds have been shown to be correlated with their electronic structures,
      namely, with the magnitude of the energy of the lowest unoccupied molecular
      orbital (LUMO). The log mutagenicity potencies for the series of 14
      benz[alpha]anthracenes are negatively dependent on E(LUMO), with a correlation
      coefficient of 0.82, which is increased to 0.90 by inclusion in the QSAR of a
      second variable, namely Q3H, the electronic density in the highest occupied
      molecular orbital, E(HOMO), of carbon-3. E(LUMO) is also negatively correlated
      with mouse carcinogenicity of the benzanthracenes, with a correlation coefficient
      of 0.88 for tumour incidence, and of 0.83 for log carcinogenicity index. The
      carcinogenicity and mutagenicity of the individual members of this series of
      polycyclic aromatic hydrocarbons are discussed in terms of the relationships
      between molecular structure, electron density, metabolic activation and covalent
      binding of reactive intermediates.

PMID- 7739603
TI  - Comparison of the mutagenicity and mutagen specificity of ethylenimine with
      triethylenemelamine in the ad-3 region of heterokaryon 12 of Neurospora crassa.
AB  - Studies have been performed to compare the mutagenicity and mutagenic specificity
      of the trifunctional alkylating agent, triethylenemelamine (TEM), and a closely
      related monofunctional agent, ethylenimine (EI), in the adenine-3 (ad-3) region
      of a 2-component heterokaryon (H-12) of Neurospora crassa. The primary objective
      of our studies was to characterize the genetic damage produced by each agent with
      regard to (1) mutagenic potency, and (2) the spectrum of specific-locus mutations
      induced in a lower eukaryotic organism. As in higher eukaryotes, specific-locus
      mutations in the ad-3 region of H-12 result from gene/point mutations, multilocus
      deletion mutations, and multiple-locus mutations. Specific-locus mutations
      resulting from gene/point mutation and multilocus deletion mutation can be
      detected in higher eukaryotes, but multiple-locus mutations can be detected only
      with difficulty or not at all. Our experiments with the ad-3 forward-mutation
      assay have demonstrated that TEM is a strong mutagen (maximum forward-mutation
      frequency between 100 and 1000 ad-3 mutations per 10(6) survivors) and EI is a
      moderate mutagen (maximum forward-mutation frequency between 10 and 100 ad-3
      mutations per 10(6) survivors) for the induction of specific-locus mutations in
      the ad-3 region. Classical genetic tests were used to identify the different
      genotypic classes and subclasses among the EI- and TEM-induced ad-3 mutations
      from each experiment. The overall data base demonstrates that both EI- and TEM
      induced ad-3 mutations result predominantly from gene/point mutations at the ad
      3A and ad-3B loci (97.3% and 95.5%, respectively), and infrequently from
      multilocus deletion mutations (2.7% and 4.5%, respectively). Heterokaryon tests
      for allelic complementation on TEM- and EI-induced ad-3B mutations, however, have
      revealed a difference between the percentages showing allelic complementation
      (63.1% and 40.9%, respectively). Based on the specific revertibility of
      complementing and noncomplementing ad-3B mutations induced by other agents, this
      difference in the percentages of ad-3B mutations showing allelic complementation
      results from a difference between the spectrum of genetic alterations at the
      molecular level. In addition, comparison of the ratio of TEM-induced ad-3A and ad
      3B mutations with those induced by EI has revealed a difference between the ad
      3B/ad-3A ratios. Additional comparisons are made of the mutagenic effects of TEM
      and EI with those of other chemical mutagens and carcinogens in the ad-3 specific
      locus assay in Neurospora.

PMID- 7739605
TI  - Relationships between electronegativity and genotoxicity.
AB  - The mean electronegativity of chemicals tested for mutagenicity, genotoxicity,
      clastogenicity and toxicity was determined. It was found that, as expected,
      chemicals with 'structural alerts' for DNA reactivity, and/or capable of inducing
      mutations in Salmonella and/or unscheduled DNA synthesis in hepatocytes, as a
      group, were significantly more electronegative than the molecules lacking these
      attributes. Molecules capable of inducing somatic mutations and recombinations in
      Drosophila melanogaster also exhibited this characteristic although it was of
      borderline statistical significance. Inducers of chromosomal aberrations and
      sister-chromatid exchanges in cultured CHO cells showed the same trend, however
      the differences between inducers and non-inducers were not statistically
      significant. In contrast to the above, inducers of bone marrow micronuclei, as a
      group, were significantly less electronegative than non-inducers. This is a
      property they shared with chemicals that exhibited systemic or cellular toxicity
      or that induced lethality in minnows. These findings suggest that in addition to
      genotoxicity, cellular and/or systemic toxicity may also contribute to the
      induction of micronuclei.

PMID- 7739606
TI  - Dominant lethal studies in male mice after exposure to a 50 Hz magnetic field.
AB  - The potential mutagenicity of power frequency magnetic fields was investigated
      using a dominant lethal assay in mice. A total of 42 male mice were exposed for 8
      weeks to a 50 Hz sinusoidal magnetic field at 10 mT (rms) and 47 males acted as
      simultaneous cage controls. Each male was subsequently mated with two females on
      weeks 1, 3, 5, 7, and 9 post-exposure. The numbers of pregnant females, corpora
      lutea, and live and dead implants were recorded. Multiple logistic regression
      analyses examined the effects of exposure on pregnancy rate, pre-implantation
      survival and post-implantation survival. There were no statistically significant
      differences in overall response between exposed and control groups, nor was there
      any significant effect of exposure in any post-exposure week. Thus, exposure to
      power frequency magnetic fields at 10 mT for the approximate period of
      spermatogenesis did not appear to induce dominant lethal mutation in the germ
      cells of male mice.

PMID- 7739607
TI  - Current issues in mutagenesis and carcinogenesis, No. 55. Activity of etoposide
      in the mouse bone marrow micronucleus test: independence of route of exposure.

PMID- 7739608
TI  - Mammalian mutants defective in the response to ionizing radiation-induced DNA
      damage.

PMID- 7739609
TI  - Biological effects of active oxygen on an X-ray-sensitive mutant mouse cell line
      (SL3-147).
AB  - The biological effects of active oxygen species were examined in a mutant mouse
      cell line (SL3-147) that is deficient in the repair of DNA double-strand breaks.
      This mutant cell line shows different sensitivities to X-rays, hydrogen peroxide,
      paraquat and menadione when compared to the wild-type cell line (LTA). SL3-147
      was more sensitive to X-rays, hydrogen peroxide and paraquat, but was less
      sensitive to menadione in side by side comparisons to LTA cells. The greater
      number of DNA double-strand breaks in SL3-147 appears to account for the line's
      greater sensitivity to X-rays and paraquat. DNA damage other than double-strand
      breaks or injury to non-DNA targets, however, is responsible for the differences
      between LTA and SL3-147 in their sensitivities to hydrogen peroxide and
      menadione.

PMID- 7739610
TI  - Repair of some active genes in Cockayne syndrome cells is at the genome overall
      rate.
AB  - Repair of UV (254 nm)-induced DNA damage in cells from patients with the genetic
      disease Cockayne syndrome (CS; CS3BE, CS2BE) has been examined in several
      different genomic regions. These regions include those that contain the actively
      transcribed beta-actin and adenosine deaminase (ADA) genes and the inactive
      insulin and 754 loci. The beta-actin, ADA and insulin regions are repaired at
      about the same rate, one which is equal to the genome overall repair rate. The
      754 locus is repaired considerably more slowly. The insulin region is repaired at
      the same rate in both CS and normal cells as is the 754 locus. The only
      difference from normal is that the active genes, while repaired well, are not
      preferentially repaired relative to the genome overall. Our results are
      consistent with the hypothesis that the repair defect in CS is due to an inactive
      transcription-repair coupling factor (TRCF). However, the results also indicate
      that factors other than TRCF and active transcription must also promote repair of
      some regions relative to others in both normal and CS cells.

PMID- 7739611
TI  - Detection of single-strand breaks and formamidopyrimidine-DNA glycosylase
      sensitive sites in DNA of cultured human fibroblasts.
AB  - Under oxidative stress 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG), a damaged
      base with mutagenic potential, and single-strand breaks (SSB) are formed in DNA.
      Both lesions are frequently used as a parameter for oxidative damage of DNA. Here
      we report on results from the evaluation of a modified nick translation assay,
      where 8-oxodG and SSB formation in cellular DNA of cultured human fibroblasts
      were simultaneously detected. The assay is based on a method previously described
      by others, with several modifications in reaction conditions and type of
      substrate. We used formamidopyrimidine-DNA glycosylase (FPG) in our assay in
      order to measure the formation of FPG-sensitive lesions (which include 8-oxodG)
      in DNA of human fibroblasts in response to ionising radiation. The quantification
      of the DNA damage was based on calibration experiments with plasmid DNA pUC19.
      Dose-response curves of SSB and FPG-sensitive lesion formation in human
      fibroblasts VH-10 were established. A very low background level of 8-oxodG was
      detected in unirradiated fibroblasts (approx. 500 residues per cell).

PMID- 7739612
TI  - The hypermutability conferred by the mus308 mutation of Drosophila is not
      specific for cross-linking agents.
AB  - The hypersensitivity of the mus308 mutant of D. melanogaster to cross-linking
      agents has been suggested to be the consequence of a possible defect of this
      mutant in DNA cross-link repair. Moreover, the mus308 mutation has been proposed
      as an animal model for the study of Fanconi's anemia. In order to obtain more
      information about the function controlled by this locus, we have measured the
      mutability of the mus308 mutant to several mutagens with different modes of
      action using the sex-linked recessive lethal test. We show that this mutation
      confers hypermutability not only to the cross-linking agents tested,
      hexamethylphosphoramide and hexamethylmelamine, but to the point mutagen N-ethyl
      N-nitrosourea as well, whereas the response to methyl methanesulfonate was
      normal. The results suggest that the mus308 locus is not defective in a repair
      pathway specific for cross-links but is rather involved in a step of a more
      general post-replication repair process responsible for the removal of non
      excised adducts.

PMID- 7739613
TI  - Interactions between photolyase and dark repair processes in Chlamydomonas
      reinhardtii.
AB  - The participation of DNA photolyase in dark repair processes has been reported in
      some heterotrophic organisms. To assess the role of photolyase in dark repair in
      photoautotrophs, double mutants of Chlamydomonas reinhardtii deficient in dark
      repair and photoreactivation were constructed and assayed for UV sensitivity in
      different posttreatment light conditions (with or without subsequent
      photoreactivation). We found that a functional PHR1 gene enhanced dark survival
      in the excision deficient (uvs9, uvs12) and in the recombination deficient
      (uvs10) genetic backgrounds but failed to do so in the strain deficient in a
      repair pathway other than excision and recombination (uvs13). Therefore we can
      conclude that photolyase may stimulate dark repair processes in C. reinhardtii
      also via pathway(s) other than nucleotide excision repair. The fact that some of
      the double mutants deficient in dark repair and photoreactivation survived better
      in the light than in the dark supports the idea that additional photorepair might
      be active and may enhance survival in a specific genetic background.

PMID- 7739614
TI  - Functional cooperation of MutT, MutM and MutY proteins in preventing mutations
      caused by spontaneous oxidation of guanine nucleotide in Escherichia coli.
AB  - 8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is a potent mutagenic
      substrate for DNA synthesis. The accumulation of 8-oxo-dGTP in the nucleotide
      pool induces G:C-->T:A transversion as well as A:T-->C:G transversion, and
      Escherichia coli cells possess mechanisms for preventing such mutations. The mutT
      gene product specifically hydrolyzes 8-oxo-dGTP to the monophosphate form while
      the mutM and the mutY gene products function to correct mispairs caused by
      incorporation of 8-oxoguanine into DNA. From analyses of forward mutations
      induced in cells lacking 8-oxo-dGTPase (MutT protein) and/or repair enzymes that
      suppress mutations caused by 8-oxoguanine in DNA (MutM and MutY proteins),
      cooperative functions of these proteins in control of the spontaneous mutagenesis
      became evident. In mutator strains lacking MutT and/or MutM proteins, 8
      oxoguanine of DNA increased to a concentration expected from the increased rate
      of mutation.

PMID- 7739615
TI  - Nitrogen mustard drug resistant B-cell chronic lymphocytic leukemia as an in vivo
      model for crosslinking agent resistance.
AB  - Acquired resistance is a limiting factor in chemotherapy. We have employed
      nitrogen mustard resistant B-cell chronic lymphocytic leukemia (B-CLL) as a
      clinically relevant model to study this phenomenon. Resistance in B-CLL is
      associated with enhanced repair of nitrogen mustard crosslinks. In order to
      identify the repair pathway responsible for nitrogen mustard resistance,
      lymphocytes were screened for cross-resistance to a variety of DNA damaging
      agents. The MTT assay was used to measure the resistance of B-CLL lymphocytes to
      various DNA damaging agents, including nitrogen mustards, UV light, methyl
      methanesulfonate, and mitomycin C. We have shown that B lymphocytes from patients
      with nitrogen mustard resistant chronic lymphocytic leukemia reflect their
      clinical status. This assay allows us to classify lymphocytes as nitrogen mustard
      sensitive or resistant, based on in vitro observations. The resistant population
      was 5.6 and 4.1 fold more resistant to the nitrogen mustard analogs, chlorambucil
      and melphalan, respectively. Resistant lymphocytes displayed no increased
      resistance to either methyl methanesulfonate or UV light, indicating that neither
      classical base nor nucleotide excision repair is rate-limiting in resistance.
      Resistant lymphocytes were 6.0 and 2.2 fold more resistant to mitomycin C and cis
      diamminedichloroplatinum (II), respectively, suggesting enhanced crosslink
      repair. Neither glutathione nor glutathione S-transferase levels correlated with
      resistance. The development of nitrogen mustard drug resistance in B-CLL appears
      to be associated with cross-resistance to other bifunctional alkylating agents
      which produce interstrand crosslinks. Our results indicate that resistance to
      nitrogen mustards in chronic lymphocytic leukemia is associated with enhanced
      repair of DNA crosslinks which may involve a recombination dependent system. This
      model should prove very useful in the elucidation of the molecular mechanisms of
      crosslink repair.

PMID- 7739616
TI  - Toxicity of camptothecin to Chinese hamster cells containing 5-hydroxymethyl-2'
      deoxyuridine in their DNA.
AB  - 5-Hydroxymethyl-2'-deoxyuridine (hmdUrd) is incorporated into the DNA of V79
      Chinese hamster cells as an analogue of thymidine. Incorporated residues are then
      recognized and excised by hmUra-DNA glycosylase (hmUDG). The removal of large
      numbers of hmUra residues and subsequent strand breakage is cytotoxic, as has
      been demonstrated by our finding that a mutant cell line, which is deficient in
      this enzyme, is resistant to hmdUrd (Boorstein et al., 1992a). In order to
      determine whether topoisomerase I plays a role in hmUDG initiated base excision
      repair, V79 cells and repair deficient V79mut1 cells were exposed to combinations
      of hmdUrd and the topoisomerase I inhibitors camptothecin (CPT), CPT-11, and beta
      lapachone. Treatment of V79 cells with hmdUrd followed by non-toxic
      concentrations of camptothecin or CPT-11 showed significant enhancement of the
      baseline cytotoxicity of the hmdUrd alone. In contrast, camptothecin and CPT-11
      had no effect in combination with hmdUrd in the V79mut1 cells. Non-toxic
      concentrations of beta-lapachone, which inhibits topoisomerase I by a different
      mechanism than camptothecin and CPT-11, produced no synergistic toxicity in V79
      cells. Neither camptothecin nor CPT-11 inhibited removal of hmdUrd from hmdUrd
      treated cells, nor did they affect hmdUrd-induced poly(ADP-ribose) synthesis.
      Camptothecin did not alter the cell cycle distribution of either hmdUrd treated
      cells or untreated cells at concentrations sufficient to cause synergistic
      toxicity with hmdUrd. Results from our study indicate that the utility of
      topoisomerase I inhibitors may be enhanced by sensitizing cells with hmdUrd
      initiated repair activity which arrests cells in S-phase and produces DNA lesions
      that are further converted into lethal damage by camptothecin.

PMID- 7739617
TI  - The pattern of mutations induced by neocarzinostatin and methyl methanesulfonate
      in the ataxia telangiectasia-like Chinese hamster cell line V-E5.
AB  - The Chinese hamster cell line V-E5 is a mutant cell line isolated from V79 cells.
      The phenotypic characteristics of V-E5 strongly resemble those of cells from
      patients suffering from the genomic instability syndrome ataxia telangiectasia.
      In order to further characterize the mutant cell line and to get insight into the
      underlying genetic defect we compared the clastogenic and mutagenic effects of
      neocarzinostatin (NCS) and methyl methanesulfonate (MMS) in V-E5 and V79 wild
      type cells (V79-LE). V-E5 cells were 2-3 times more sensitive to the cytotoxic
      effect of NCS or MMS. The clastogenic action of NCS was characterized by the
      predominant induction of chromosome breaks and dicentrics in both cell lines,
      whereas MMS mainly induced chromatid-type aberrations. The frequency of mutations
      induced by NCS as well as MMS was slightly enhanced in V-E5 cells compared to V79
      cells treated with the same dose. However, the mutant cell line was found to be
      hypomutable when considering the same survival level as in the parental cell
      line. Molecular analysis of mutants induced by NCS revealed a high frequency of
      total deletions of the hprt gene in both cell lines. In contrast, among MMS
      induced mutations only 11% deletion mutations were found in V79-LE, whereas in V
      E5 MMS-induced deletions were seen in 52% of the hprt-deficient mutants. These
      results are discussed with respect to a possible relation between genomic
      instability, cell cycle control and mutational spectra.

PMID- 7739618
TI  - International Symposium on Facioscapulohumeral Muscular Dystrophy, Clinical and
      Molecular Genetic Aspects of the Disease. Kyoto, Japan, July 10, 1994.

PMID- 7739619
TI  - Phenotypic-genotypic correlation will assist genetic counseling in 4q35
      facioscapulohumeral muscular dystrophy.
AB  - The wide range of severity in facioscapulohumeral muscular dystrophy (FSHD)
      complicates genetic advice, although onset age is youngest and severity is
      greatest in isolated cases. From 14 of 16 large FSHD families which are 4q35
      linked, and from 25 of 34 isolated cases exhibiting a de novo D4F104S1 DNA
      fragment, we find a correlation between proband age at onset and FSHD-associated
      D4F104S1 fragment size (r = 0.56; P < 0.001), with the smallest fragments
      occurring in isolated cases. A 4q35-linked 38-kb fragment in one family supports
      scapulohumeral presentation without facial involvement as a milder late-onset
      variant of FSHD, and with apparent "unaffected" recombinants in small families,
      suggests that nonpenetrance is more likely with large fragment sizes. Our
      results, predicting a more limited range for severity within families, and
      suggesting > 85% of FSHD maps to 4q35, will facilitate genetic counseling. We
      propose that quantitative variation in a uniform mutation mechanism influences
      age at onset, but by deletion rather than expansion of DNA.

PMID- 7739620
TI  - Fish mapping of 250 cosmid and 26 YAC clones to chromosome 4 with special
      emphasis on the FSHD region at 4q35.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is located on chromosome 4q35,
      close to the telomere. FSHD patients carry deletions within a cluster of tandemly
      repeated DNA. Although expression of a functional FSHD gene will be altered in
      patients, the sequence itself may be unaffected by this deletion. Hence, the FSHD
      gene could lie outside of the deleted region. This study employs fluorescent in
      situ hybridization using chromosome 4-specific cosmid and YAC clones to rapidly
      saturate chromosome 4 with new markers. Some 250 cosmids and 26 YACs were
      regionally mapped, of which 5 YACs and 55 cosmids mapped to the distal portion of
      4q. Only one of these clones (D4S1454) mapped telomerically to a translocation
      breakpoint specified by D4S187. Using two-color interphase mapping, the following
      marker order was obtained: Cen-D4S187-D4S1454-HSPCAL2-D4S163-D4S139-+ ++D4F35S1.
      Absence of additional markers mapping distal to D4F35S1 indicates that the
      linkage group containing the FSHD gene lies extremely close to the 4q telomere.

PMID- 7739621
TI  - Search for the FSHD gene using cDNA selection in a region spanning 100 kb on
      chromosome 4q35.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is caused by deletions of 3.3-kb
      tandemly repeated units contained within a large polymorphic EcoRI fragment close
      to the telomere of chromosome 4q. Since the rearrangements were assumed to
      interfere with the structure or function of the putative FSHD gene, the gene
      search was focused on cosmids containing these repeat units and, in addition,
      cosmids spanning 75 kb of upstream sequences. cDNA selection hybridization was
      applied to four overlapping cosmid clones, yielding a total of 150 putative cDNA
      clones. These clones showed a random distribution across the cosmid contig,
      except for three regions which contained a much larger number of clones. Nine
      cDNA clones hybridized to a 2.2-kb EcoRI fragment, located 22 kb centromeric to
      the 3.3-kb repeated units. This 2.2-kb fragment showed evolutionary conservation,
      and analysis of the sequence by "GRAIL" predicted the presence of several exons.
      Transcripts homologous to this fragment could be identified but none of them
      originated from the 4q35 locus. Strikingly, most clones revealed 4-10 homologous
      loci, and no single copy clones could be isolated. These findings are in line
      with earlier observations by fluorescent in situ hybridization (FISH) showing
      hybridization of individual cosmid clones to multiple chromosomes. The presence
      of homologous regions on other chromosomes seriously complicates the cloning of
      the FSHD gene.

PMID- 7739622
TI  - Cloning and mapping of a very short (10-kb) EcoRI fragment associated with
      facioscapulohumeral muscular dystrophy (FSHD).
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is a dominantly inherited muscular
      disorder and the gene for FSHD has been mapped to chromosome 4q35. Recently, the
      DNA rearrangements associated with the disease were found in the EcoRI fragment
      detected by the probes p13E-11 and pFR-1, and deletions of the 3.3-kb KpnI repeat
      units within the EcoRI fragment are thought to cause the disease. In this study,
      we cloned the FSHD-associated EcoRI fragments (the shortest fragments identified
      to date: 10 kb) from 2 severely affected patients (unrelated). Restriction enzyme
      maps of the genomic fragments in the 2 patients revealed that the 10 kb fragments
      were identical and contained only one 3.3-kb KpnI repeat unit. These results
      suggest that deletions of the 3.3-kb KpnI repeat units are likely to associate
      with FSHD, and that the 10 kb fragments may provide a means of understanding the
      molecular details involved at the site of the chromosomal rearrangements in FSHD.

PMID- 7739623
TI  - Efforts toward understanding the molecular basis of facioscapulohumeral muscular
      dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder
      with a frequency of 1 in 20,000. The report in 1992 of a DNA polymorphism that
      occurred both in familial and sporadic cases led to the pronouncement that the
      FSHD defect had been identified. Unfortunately, 2 years have passed without the
      isolation of a gene or definitive proof of the mutation. Over this time it has
      become clear that the region of the human genome containing the FSHD gene is a
      complex assemblage of mildly repetitive sequences that includes the suspected
      polymorphic fragment. We have employed molecular and cytogenetic techniques to
      initiate the structural analysis of terminal 4q35 in an effort to facilitate the
      isolation of the gene responsible for FSHD. As a result of these efforts and our
      inability to identify expressed sequences unique to 4q35 we have begun to
      consider alternate hypotheses for a molecular mechanism resulting in FSHD other
      than a simple coding sequence disruption.

PMID- 7739624
TI  - The FSHD-linked locus D4F104S1 (p13E-11) on 4q35 has a homologue on 10qter.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) has recently been shown to be
      associated with deletions that are detectable using probe p13E-11 (D4F104S1).
      Although these deletions reside within large, highly polymorphic restriction
      fragments (20-300 kb), the "mutant" fragment is usually shorter than 28 kb and
      can routinely be detected using conventional agarose gel electrophoresis. Yet,
      the complete visualization of the alleles requires pulsed-field gel
      electrophoresis (PFGE). Family studies showed that p13E-11 detects two nonallelic
      loci in this size range, only one of which originates from chromosome 4q35. We
      have assigned the other p13E-11 locus to chromosome 10qter by linkage analysis in
      CEPH pedigrees. Knowing the location of both loci improves the diagnostic
      reliability, as the exact origin of "small" EcoRI fragments can be determined by
      haplotyping. Since FSHD shows genetic heterogeneity, this 10qter locus became an
      interesting candidate to be the second FSHD locus. However, analysis of a large
      chromosome 4-unlinked FSHD family did not provide evidence for linkage on
      chromosome 10qter.

PMID- 7739625
TI  - Germinal mosaicism in facioscapulohumeral muscular dystrophy (FSHD).
AB  - Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant neuromuscular
      disorder with a prevalence of 1 in 20,000. The DNA marker p13E-11 (D4F104S1)
      detects a de novo DNA rearrangement in the majority of sporadic and FSHD cases.
      These rearrangements consist of deletions of multiple copies of tandem repeat
      (D4Z4). We have studied 34 new mutation FSHD families of which 26 showed a de
      novo fragment with p13E-11. In three of the remaining eight families without a de
      novo fragment, germinal mosaicism was noted. In each case, the proband had
      inherited a small EcoR1 fragment from the clinically unaffected mother; however,
      the hybridization signal intensity of this fragment in the mother's DNA was
      significantly reduced in all three families. This is the first study to describe
      such mosaicism in FSHD families using DNA analysis and therefore has a
      considerable significance for genetic counseling and prenatal diagnosis.

PMID- 7739626
TI  - Monozygotic twins with facioscapulohumeral dystrophy (FSHD): implications for
      genotype/phenotype correlation. FSH-DY Group.
AB  - Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant disorder with a
      characteristic and distinctive distribution of weakness but a high degree of
      variation in the age of onset and rate of progression. Monozygotic twins provide
      the opportunity to assess the relative importance of genetic as opposed to
      nongenetic influences on the course of disease. We have studied three sets of
      monozygotic twins with FSHD and compared the similarity of their degree of
      involvement using quantitative studies of individual muscle function. Similar
      quantitative studies of 59 other subjects with FSHD served as a reference
      population for contrast with the twin studies. One set of twins was discordant
      for FSHD, presumably as a reflection of a postzygotic mutation in the affected
      twin. The other two sets were concordant and both had evidence of autosomal
      dominantly inherited gene rearrangements. Both sets were similarly affected in
      terms of age of onset, overall degree of disability, and quantitative tests of
      muscle, but there were major differences in the symmetry of involvement of
      specific muscles. Cerebral dominance was not related to asymmetries of
      involvement. These data suggest age of onset and severity are determined by the
      gene lesion in FSHD. Other factors may influence the frequently encountered
      asymmetries in FSHD.

PMID- 7739627
TI  - Inflammatory response in facioscapulohumeral muscular dystrophy (FSHD):
      immunocytochemical and genetic analyses.
AB  - To investigate the nature of the inflammatory response in facioscapulohumeral
      muscular dystrophy (FSHD), we analyzed mononuclear cells in muscle sections
      obtained from 18 FSHD patients and 8 controls. Monoclonal antibodies reactive for
      T cells, T cell subsets, B cells, and NK cells were used for cell typing.
      Macrophages were identified by acid phosphatase reaction. The localization of
      perforin, granzyme A, MHC-I and -II, dystrophin, and alpha-actinin antigens was
      also examined. We found that all FSHD patients, both familiar and sporadic cases,
      had greater amounts of mononuclear cellular infiltrates in muscle than controls,
      in whose specimens only few extra vascular mononuclear cells were counted.
      Seventy-two percent (13 of 18) of the patients had more than 50 inflammatory
      mononuclear cells per 1000 muscle fibers, and 33% (6 of 18) patients had numerous
      inflammatory cells exceeding 600 per 1000 muscle fibers (1835 +/- 482 SE).
      Nonnecrotic fibers invaded by mononuclear cells with either T8+, perforin+, or
      granzyme A+ were not observed in FSHD, while a few degenerating fibers were
      superficially invaded by T cells and macrophages. Occasional T cells were
      observed moving through the blood vessel wall. The increased number of necrotic
      fibers was paralleled by an increased number of inflammatory cells (r = 0.783, P
      = 0.0001). Genetic analysis, using the probes p13E-11, pFR-1, D4S139, and D4S163,
      was done in 6 patients (3 familiar, 3 sporadic) who had numerous inflammatory
      infiltrates. These 6 patients had small (< 28 kb) EcoRI fragments associated with
      the disease, and the disease was linked to 4q35. These results suggest that, in
      chromosome 4-linked FSHD: (1) inflammatory changes in muscle are a common
      histological feature; (2) mononuclear cellular infiltrates may enhance muscle
      fiber damage; but (3) T-cell-mediated cytotoxicity directed against muscle fibers
      is unlikely. We speculate that the immune effector mechanism in FSHD is different
      from that in previously reported inflammatory myopathies and Duchenne muscular
      dystrophy.

PMID- 7739628
TI  - Characterization of a tandemly repeated 3.3-kb KpnI unit in the
      facioscapulohumeral muscular dystrophy (FSHD) gene region on chromosome 4q35.
AB  - A 3.3-kb KpnI repeat unit within the tandem repeat locus (D4Z4) and its upstream
      2.5-kb HincII/KpnI fragment of the facioscapulohumeral muscular dystrophy (FSHD)
      gene region at 4q35-qter were sequenced and characterized. The 3.3-kb KpnI unit
      was 3303 bp in length and contained two homeodomain sequences, one LSau-like
      sequence, and several microsatellites. The GC content in the 3.3-kb unit was very
      high (73%), while it was only 35% in the nonrepeated region of the 2.5-kb
      fragment. We identified 99% homologous sequences (918 bp) in the 3' end of the
      3.3- and 2.5-kb fragments. These findings suggested that the repeated sequences
      at the D4Z4 start from 918 bp upstream to the first KpnI site.

PMID- 7739629
TI  - Early onset facioscapulohumeral muscular dystrophy.
AB  - We report 10 patients (5 familial, 5 sporadic) with facioscapulohumeral muscular
      dystrophy (FSHD) with onset of facial and shoulder girdle weakness in early
      infancy. They showed the same broad range of clinical signs and symptoms as can
      be seen normally in FSHD. In 7 patients Southern blotting with p13E-11 was
      performed which showed an abnormal EcoRI fragment (13-22 kb) in 6 of them. We
      conclude that early onset FSHD does not differ from regular FSHD clinically or
      genetically. However, the precise mechanisms involved in the extensive clinical
      variability of the disease are still unknown.

PMID- 7739630
TI  - On the significance of retinal vascular disease and hearing loss in
      facioscapulohumeral muscular dystrophy.
AB  - We have performed retinal fluorescein angiography and audiometry in 32 familial
      and 7 sporadic cases of facioscapulohumeral muscular dystrophy. A mild to
      moderate retinal vasculopathy, consisting of retinal teleangiectasis and
      microaneurysms, was present in 18 of 37 evaluable angiograms (49%); 5 patients
      had minimal changes and 14 angiograms (38%) were normal. High frequency hearing
      loss was found in 25 (64%) out of 39 patients. Retinal changes were absent in 5
      of 18 families (6 cases examined), and after correction for age and sex, hearing
      function was normal in 5 of 19 families (7 cases examined). Age and severity of
      the myopathy did not have a clear relationship with the retinal vasculopathy or
      the hearing loss. There were no differences between families in which the
      myopathy was linked to chromosome 4q35 and families in which linkage could not be
      proven. Minimal retinal vascular changes and high tone hearing loss can be
      observed occasionally in the normal population. Therefore, although retinal
      vasculopathy and hearing loss are part of the clinical picture of FSHD, these
      signs cannot be accepted as decisive criteria for FSHD in clinically equivocal
      cases.

PMID- 7739631
TI  - Facioscapulohumeral muscular dystrophy in the Dutch population.
AB  - Extrapolating the figures from a previous study on FSHD in a province of The
      Netherlands to the entire Dutch population suggests that at present a nearly
      complete overview is obtained of all symptomatic kindred. In 139 families,
      dominant inheritance was observed in 97, a pattern compatible with germline
      mosaicism in 6, while sporadic cases were found in 36 families. A mutation
      frequency of 9.6% was calculated. Mental retardation and severe retinal
      vasculopathy were reported in low frequencies (1%). Early onset was seen more
      frequently in sporadic cases. Chromosome 4 linkage appeared excluded in 3 of 22
      autosomal-dominant families. The clinical pictures in the linked and nonlinked
      families were identical.

PMID- 7739632
TI  - Clinical variability of facioscapulohumeral muscular dystrophy in Russia.
AB  - One hundred forty-two patients (66 men and 76 women) from 20 autosomal-dominant
      pedigrees and 3 families including 5 "sporadic" cases were examined. A great
      similarity of clinical manifestations among those affected was noted. Clinical
      variability of phenotypes reflecting various phases of the disease and different
      expressions of the mutant gene were always within the limits of the identical
      final phenotype of the disease, namely the facio-scapulo-humero-peroneal-femoro
      (posterior group of the muscles)-gluteal (gluteus maximus). Thus, the clinically
      and genetically homogeneous group of patients with autosomal-dominant descending
      with a "jump" form of facioscapulohumeral dystrophy (FSHD), called
      facioscapuloperoneal dystrophy (FSPD), was examined. Among the observed cases we
      did not come across any having the autosomal-dominant gradually descending form
      of FSHD, called facioscapulolimb dystrophy (FSLD), in which the pelvic and
      proximal lower limb muscles get weak earlier than in the peroneal group (anterior
      tibial) muscles. We could not reveal the "pure" facioscapulohumeral phenotype of
      muscle weakness in 142 examined patients. A "pure" FSHD does not exist as a
      nosological entity. It represents only the syndrome which characterizes the
      initial phase of FSLD, but not of the FSPD. It is quite probable that FSPD and
      FSLD which may be differentiated clinically are two different diseases connected
      with the mutation of allelic or even different genes. Linkage studies in FSPD and
      FSLD mapping genes would confirm this data.

PMID- 7739633
TI  - Neurogenic FSH muscular atrophy.
AB  - Neurogenic facioscapulohumeral (FSH) muscular atrophy is a distinct entity from
      FSH muscular dystrophy. Is the gene(s) responsible for the disease identical with
      or different from that for FSH dystrophy?

PMID- 7739634
TI  - Mouse myodystrophy (myd) mutation: refined mapping in an interval flanked by
      homology with distal human 4q.
AB  - Myodystrophy (myd) is an autosomal-recessive mouse mutation with dystrophic
      skeletal muscle. We propose that myd may be a model of the human disorder
      facioscapulohumeral dystrophy (FSHD) on the basis of clinical features and
      homologous genetic map locations. FSHD maps to human 4q35, while myd maps to
      mouse chromosome 8. To explore the relationship between FSHD and myd, it is
      necessary to define the homologous regions of human chromosome 4 and mouse
      chromosome 8, and ultimately, identify the genes underlying both disorders. A
      kallikrein gene (Kal3) was previously mapped by in situ hybridization to mouse
      chromosome 8 and human 4q35. We report the genetic map location of Kal3, bringing
      to 4 the number of genes with homologues on human 4q31-35 placed on the genetic
      map of mouse chromosome 8. As a first step in gene isolation, we have narrowed
      the interval containing myd by typing 125 affected mice with microsatellite
      markers. Analysis of recombinants placed myd in an interval that is flanked by
      genes with homologues in human 4q.

PMID- 7739635
TI  - Transcranial magnetic stimulation of the trigeminal nerve: intraoperative study
      on stimulation characteristics in man.
AB  - We studied responses from the masseter and nasalis muscles following magnetic
      stimulation (magStim) and compared these responses with those obtained by direct
      electrical stimulation of the trigeminal (NV) and facial (NVII) nerve near the
      root exit zone during microvascular decompression operations of NVII. We found
      that (1) magStim threshold to excite the nerve is high for NV and low for NVII;
      (2) excitation of all motor fibers is impossible for NV, and easy for NVII; (3)
      optimal coil placement is critical for NV, but not critical for NVII; and (4)
      between and within subjects, the excitation site is variable on NV, but stable on
      NVII. We estimated that the anatomical location of magStim to be either within or
      outside the cerebrospinal fluid for NV, and to be in the labyrinthine segment of
      the facial canal for NVII. Physical models explain and clinical lesion models
      support these differences found between NV and NVII.

PMID- 7739636
TI  - Maximal force and endurance to fatigue of respiratory and skeletal muscles in
      chronic hypoxemic patients: the effects of oxygen breathing.
AB  - The consequences of chronic hypoxemia on maximal force and endurance time to
      sustained 80% of maximal isometric contraction of two skeletal muscles (adductor
      pollicis and vastus lateralis) and the diaphragm were studied in patients with
      chronic obstructive pulmonary disease (COPD). Compared to normal subjects, COPD
      patients have lower values of Fmax for the two skeletal muscle groups and Pmax
      (diaphragm). Endurance time was also shorter for the diaphragm and adductor
      pollicis. Chronic hypoxemia was associated with an accentuation in integrated EMG
      changes in both low and high frequency bands for adductor pollicis and diaphragm.
      Inhalation of oxygen enriched gas mixture for a 15-min period increased markedly
      Fmax and PImax values, prolonged the endurance time to sustained thumb adduction,
      and reduced the EMG changes in the low frequency band for adductor pollicis. The
      present observations provide evidence for altered maximal performances of
      skeletal muscles in chronic hypoxemic patients and also point out the virtues of
      oxygen breathing in these patients.

PMID- 7739637
TI  - Stimulation distal to the lesion in patients with carpal tunnel syndrome.
AB  - In patients with carpal tunnel syndrome, low action potential amplitude after
      stimulation at the wrist (proximal to the lesion) is due to either demyelination
      or axonal degeneration. Demyelination can be distinguished from axonal
      degeneration by the presence of amplitude drop across the lesion. Amplitude drop
      is determined by comparison of action potential amplitude evoked by stimulation
      at the palm (distal to the lesion) with that of the wrist. Of 59 consecutive CTS
      patient hands, 36 (61%) showed significant reduction in CMAP and/or antidromic
      SNAP amplitudes at the wrist compared to the palm, indicating the presence of
      focal demyelination resulting in conduction block vs. pathologic dispersion with
      phase cancellation. Moreover, the smaller the wrist-evoked action potential
      amplitude, the greater the amplitude drop across the lesion. We conclude that in
      patients with CTS, as in other entrapment neuropathies, stimulation both proximal
      and distal to the lesion provides important pathophysiological information about
      the median nerve lesion.

PMID- 7739638
TI  - Three-dimensional MR imaging of brain surface anomalies in Fukuyama-type
      congenital muscular dystrophy.
AB  - Fukuyama-type congenital muscular dystrophy (FCMD), the second most common
      childhood muscular dystrophy in Japan, is characterized by the association with
      severe brain anomalies such as pachygyria and focal interhemispheric fusion.
      Conventional imaging techniques such as X-ray CT scan and MRI are ineffective for
      visualization of these brain surface anomalies. Here we investigated the efficacy
      of three-dimensional (3-D) reconstruction of brain surface MR images for the
      detection of brain anomalies in FCMD patients. 3-D brain surface MR images
      clearly visualized anomalies of cerebral gyrus such as pachygyria, as well as
      focal interhemispheric fusion. In addition, reconstructed horizontal images
      visualized structural derangement such as abnormal protrusion of white matter
      into gray matter. MR image abnormalities were confirmed by autopsy in 1 patient.
      These abnormalities were never observed in Duchenne muscular dystrophy (DMD)
      patients. Our results indicate the efficacy of the present method for the
      differential diagnosis between FCMD and DMD with severe mental retardation, which
      is essential for the genetic study to identify the causative gene of FCMD.

PMID- 7739639
TI  - Median/ulnar premotor potential identification and localization.
AB  - A small negative waveform is known to precede the median and ulnar compound
      muscle action potentials when recorded with surface or concentric needle
      electrodes. This investigation documents that there are two distinct waveforms
      preceding the median compound muscle action potential (CMAP) depending upon the
      type of recording electrodes used (concentric needle versus surface) and their
      respective locations. The negative waveform originally described with a
      concentric needle electrode positioned within the substance of the distal thenar
      eminence and having a restricted zone of detection is referred to as the
      intramuscular nerve action potential (INAP). This potential is shown to be
      distinct from the premotor potential (the small negative waveform preceding
      surface recorded ulnar and median CMAPs). Detection of the median and ulnar
      premotor potentials at multiple locations about the hand with the same respective
      onset/peak latencies and amplitudes substantiates that this potential is a far
      field potential. The median and ulnar premotor potentials most likely originate
      from a dipolar moment imbalance generated by digital sensory nerve action
      potentials as they cross the first and fifth metacarpophalangeal junctions,
      respectively. Applying far-field principles permits the documentation of
      additional far-field potentials as they are generated at the second through
      fourth metacarpophalangeal junctions following median nerve stimulation. Also,
      because the premotor potential is a far-field potential, caution must be
      exercised with respect to its diagnostic utility as joint position and other
      unknown factors may affect amplitude and onset/peak latency. The INAP following
      median nerve excitation, however, is documented to be a near-field potential
      distinct from the premotor potential arising from the recurrent branch of the
      median nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7739640
TI  - Thoracic outlet syndrome--a functional disturbance of the thoracic upper
      aperture?
AB  - We describe a young woman with typical neurovascular symptoms of thoracic outlet
      syndrome (TOS). A three-dimensional computerized scan showed a "dislocation" of
      the first rib at the costotransverse joint. The patient responded to a
      conservative approach to treatment. The patient presented here demonstrates the
      functional compromise of the upper thoracic aperture that is frequently seen in
      young women.

PMID- 7739641
TI  - Disseminated histoplasmosis presenting as myositis and fasciitis in a patient
      with dermatomyositis.
AB  - A 54-year-old man with dermatomyositis initially responsive to corticosteroids
      and methotrexate developed severe myalgias, increasing weakness, and fevers.
      Laboratory studies were suggestive of disseminated histoplasmosis, and muscle
      biopsy revealed myositis, fasciitis, and yeast in the perimysial connective
      tissue. Histoplasma capsulatum was cultured from skeletal muscle. Despite
      antifungal therapy, necrotizing fasciitis progressed to gluteal abscess
      formation. Disseminated histoplasmosis may present atypically in
      immunocompromised hosts as fasciitis and myositis. Patients with dermatomyositis
      could be particularly vulnerable to soft tissue invasion by fungi due to their
      underlying microangiopathy.

PMID- 7739642
TI  - Sporadic ALS and chromosome 22: evidence for a possible neurofilament gene
      defect.
AB  - ALS is associated with the P2 blood group phenotype. Molecular evidence now shows
      the gene encoding this antigen to be on the long arm of human chromosome 22 near
      the newly discovered gene for heavy neurofilament (NF-H). Since an ALS-type
      condition can be generated in transgenic mice expressing the human NF-H gene, and
      since the gene for the CNTF-related cytokine leukemia inhibitory factor (LIF) is
      located adjacent to this gene, it is hypothesized that a defect on the chromosome
      22 band region q12 is involved in the pathogenesis of sporadic ALS.

PMID- 7739643
TI  - Neurofilaments, free radicals, excitotoxins, and amyotrophic lateral sclerosis.
AB  - There is increasing evidence implicating abnormalities of neurofilament function
      in the pathogenesis of amyotrophic lateral sclerosis (ALS). The observation that
      the P2 blood protein phenotype is overrepresented in patients with ALS is
      potentially important, but needs confirmation. It should be shown that this
      segregation is selective for ALS. If it is, the implications outlined in Meyer's
      hypothesis will need to be explored, bearing in mind that much of the evidence
      implicating excitotoxins, free radicals, and neurofilaments in familial and
      sporadic ALS is still circumstantial. Thus the identification of candidate genes,
      the pursuit of large segregation studies, and identification of specific point
      mutations, remain key goals in ALS research.

PMID- 7739644
TI  - Phenotypic heterogeneity in familial inclusion body myopathy.

PMID- 7739645
TI  - Distribution of androgen receptors in bulbospinal muscular atrophy.

PMID- 7739646
TI  - Absence of F-waves as an early electrodiagnostic finding in infarction of the
      conus medullaris.

PMID- 7739647
TI  - Does voluntary muscle contraction cause facilitation of peripherally evoked
      compound motor action potentials?

PMID- 7739648
TI  - Proximal myotonic myopathy.

PMID- 7739649
TI  - Electrophysiologic follow-up after cervical cord infarction.

PMID- 7739650
TI  - Dorsal ulnar sensory neuropathy in a heroin abuser.

PMID- 7739651
TI  - One hundred years ago: the history of cryptococcosis in Greifswald. Medical
      mycology in the nineteenth century.
AB  - Medico-mycological investigations began at Greifswald in Germany as early as 1842
      when Wilhelm Baum (1799-1883) was appointed to the chair of surgery of the
      university. This is shown by some theses of the time, as well as by the discovery
      of the contagious nature of pityriasis versicolor by Carl Ferdinand Eichstedt
      (1816-92), who identified a fungus as the cause (1846), later named Microsporon
      furfur (C. Robin 1853). In 1868 the physician Karl Friedrich Mosler (1831-1911)
      published clinical-mycological studies and investigations about animal feeding
      with yeasts. Some time later (1870) Friedrich Grohe (1830-86) and his assistants,
      Alwin R.A. Block (1843-?) and M.R. Roth of the Pathological Institute, described
      the results of transmission studies with 'Aspergillus glaucus, Penicillium
      glaucum and yeast'. His successor in the chair, Paul Grawitz (1850-1932), also
      published the results of his own mycological investigations. Finally, on 7 July
      1894, at an evening lecture of the Greifswald Medical Society, Abraham Buschke
      (1868-1943) from the Hospital of Surgery gave a talk 'on a peculiar disease
      caused by coccidia', which was followed by a talk by the pathologist Otto Busse
      (1867-1922) on a 'demonstration of a pathogenic coccidia species'. Busse's
      subsequent publications are the first proper descriptions of cryptococcosis (1894
      ff.). However, Cryptococcus neoformans was named after F. Sanfelice, whose
      results were published later (1895).

PMID- 7739653
TI  - Prophylaxis of Candida and Aspergillus infections with oral administration of
      itraconazole.
AB  - The broad-spectrum oral triazole antifungal, itraconazole, has been shown to be
      effective in the treatment of superficial and systemic infections with fungi
      including Candida albicans, C. krusei and C. glabrata, Cryptococcus, Aspergillus,
      Histoplasma, Blastomyces and others. Its broad spectrum of activity, high and
      persistent tissue levels and favourable safety profile suggest that it may be
      appropriate for the prevention of opportunistic fungal infections in at-risk
      patients. In this study, itraconazole's prophylactic efficacy was tested against
      experimental models of Candida and Aspergillus infection. A single dose of 1.25
      mg kg-1 or 2.5 mg kg-1, given 1 h before vaginal infection with C. albicans,
      protected 50% of treated rats. In systemic and disseminated candidosis,
      prophylaxis with itraconazole reduced both folliculitis and organ Candida content
      in guinea pigs. Amphotericin B was also used in this study and was found to be
      less efficacious than itraconazole. Itraconazole prolonged survival when
      administered to guinea pigs before experimental induction of systemic and
      invasive aspergillosis. In all cases, increasing the itraconazole dosage
      increased its prophylactic efficacy. Therefore, as the clinical efficacy of
      itraconazole is accurately reflected by the results of animal models, this study
      shows itraconazole to be a potential prophylactic therapy for patients at risk of
      opportunistic fungal infection.

PMID- 7739652
TI  - Pathogenicity of strains of the black yeast Exophiala (Wangiella) dermatitidis:
      an evaluation based on polymerase chain reaction.
AB  - Strains of Exophiala dermatitidis, mainly originating from patients with systemic
      neurotropic mycosis in Asia and from the lungs of patients with cystic fibrosis
      (CF) in Europe, were analysed by ribotyping of the small subunit rDNA and by
      random amplification of polymorphic DNA (RAPD). A characteristic banding pattern
      for the species was found after restriction analysis of amplified fragments V9
      and ITS4. The small subunit rDNA gene of five strains was about 1800 base pairs
      (bp) long, while in 16 strains its length was about 3000 bp. Using RAPD, seven
      populations could be distinguished. European CF strains as well as Asian strains
      from systemic mycoses are mainly distributed over two populations, one of which
      contained both CF strains and a systemic strain. It is concluded that the two
      clinical pictures are caused by genetically similar strains. The differences in
      pathogenicity may be explained by immunological differences in the hosts or by
      differences in exposure to the fungal propagules.

PMID- 7739654
TI  - White piedra and Trichosporon species in equatorial Africa. I. History and
      clinical aspects: an analysis of 449 superficial inguinal specimens.
AB  - White piedra is a hair infection characterized by nodules composed of fungal
      elements which envelop the hair shaft. Classically, this infection was considered
      to be produced by an asexual yeast-like fungus, Trichosporon beigelii. At
      present, in accordance with studies carried out previously, this species is
      subdivided into six newly defined distinct species (T. asahii, T. ovoides, T.
      inkin, T. mucoides, T. asteroides and T. cutaneum), all belonging to the class
      Basidiomycetes. Although widespread, white piedra has not previously been
      described in tropical regions of Africa. The present study, carried out in
      Libreville (Gabon), an equatorial region of Africa, shows that the incidence of
      this infection is quite high (18% of 449 inguinal specimens) in the female
      population aged 15-60 years, with a predominance in young patients (15-44 years).
      The relationship between the clinical manifestations and the specific hair
      lesions is also detailed. Three species belonging to the genus Trichosporon were
      identified: T. mucoides, T. asahii and T. inkin.

PMID- 7739655
TI  - White piedra and Trichosporon species in equatorial Africa. II. Clinical and
      mycological associations: an analysis of 449 superficial inguinal specimens.
AB  - Eighty-one of 449 Gabonese female patients examined were found to be positive for
      genitopubic white piedra. The association with trichobacteriosis is frequent (53
      cases), and mostly seen with inguinal intertrigo. Fifty-two strains belonging to
      the genus Trichosporon were isolated from genital hairs as well as from inguinal
      intertrigo lesions. These strains were identified in accordance with previously
      defined morphological and biochemical criteria. Three species were recognized: T.
      mucoides (25 strains), T. inkin (20 strains) and T. asahii (seven strains). Their
      macroscopic and microscopic morphological properties, as well as their ability to
      reduce tetrazolium, were determined. In addition, the study of the clinical and
      pathogenic associations in which each of these strains was involved revealed some
      of their particular properties.

PMID- 7739656
TI  - White piedra and Trichosporon species in equatorial Africa. III. Identification
      of Trichosporon species by slide agglutination test.
AB  - Fifty-two Trichosporon strains isolated from Gabonese female patients 15-60
      years, were studied. The identity of these strains was established by two
      different methods: the method proposed by Gueho et al. (1992), based on
      mycological criteria, and a slide agglutination method performed with
      monospecific antisera prepared in our laboratory. The final results show a
      perfect correlation between the two methods, which allowed us to identify 25
      strains of T. mucoides, 21 strains of T. inkin and seven strains of T. asahii.
      The results of the agglutination tests performed with 24-h-old subcultures grown
      on Sabouraud glucose agar are available in less than 15 mins. In the light of
      these results, it appears that this method, which is rapid and easy to perform
      and reproduce, may readily be used in hospital laboratories. In addition, this
      method allowed us to verify the presence of antigens common to the genera
      Cryptococcus and Trichosporon, which were easily shown by the use of crude sera.
      The fact that the anti-Trichosporon monospecific sera lose their capacity to
      agglutinate Cryptococcus neoformans proves their high specificity.

PMID- 7739657
TI  - Purification and characterization of protease enzymes of Basidiobolus and
      Conidiobolus species.
AB  - The protease enzymes produced by one strain of each of Basidiobolus haptosporus,
      B. ranarum and Conidiobolus coronatus were purified by precipitation and Sephadex
      G-100 gel filtration chromatography. The enzymes prepared were characterized in
      terms of their specific activities and temperature and pH optima as well as their
      molecular weights. All three fungi produced one protease of 23,000 Da molecular
      weight. Conidiobolus coronatus additionally secreted a second protease of 32,000
      Da molecular weight.

PMID- 7739658
TI  - Aspergillus chevalieri (Mangin) Thom and Church: a new opportunistic pathogen of
      human cutaneous aspergillosis.
AB  - Three cases of opportunistic cutaneous aspergillosis caused by Aspergillus
      chevalieri are described. The lesions were erythematous and hyperkeratotic with
      vesicopapular eruptions and scaling. Histopathology revealed granulomatous
      reaction showing polymorphonuclear leucocytes around fungal hyphae, which were
      broad, septate, branched and aggregated in the epidermal area. Oxiconazole and
      amorolfine, with a minimum inhibitory concentration of 10 micrograms ml-1, were
      the most active drugs against A. chevalieri 'in vitro'. A. chevalieri is, for the
      first time, documented as opportunistic pathogen of man.

PMID- 7739659
TI  - Disseminated cryptococcosis in a patient with AIDS.
AB  - We report the case of a 31-year-old AIDS patient who had generalized cryptococcal
      disease with involvement of the lungs, bone marrow, gastrointestinal tract and
      skin as well as chorioretinitis which may have been due also to Cryptococcus
      neoformans infection. Initially there was no involvement of the central nervous
      system. The patient recovered after 43 days' treatment with fluconazole and
      amphotericin B and flucytosine initially. Four months later he presented with a
      cryptococcal splenic abscess despite secondary prevention with fluconazole and
      twice-weekly liposomal amphotericin B. After splenectomy the patient was
      discharged in good health. One year later he died of cryptococcal meningitis.

PMID- 7739660
TI  - A case of sporotrichosis treated successfully with oral fluconazole 200 mg once
      weekly.
AB  - A case of fixed cutaneous sporotrichosis that developed on the extensor aspect of
      the left wrist of an 83-year-old woman was treated once a week with 200 mg of
      oral fluconazole. This dermatological lesion healed within 4 months, leaving a
      scar. No side-effects were seen. At the time of writing, 7 months after the end
      of treatment, there has been no recurrence. Reports on the efficacy of once
      weekly fluconazole administration in cases of sporotrichosis have appeared, but
      it would be valuable to study more such cases.

PMID- 7739661
TI  - In vitro susceptibility of 545 isolates of Candida spp. to four antifungal
      agents.
AB  - The in vitro susceptibility to amphotericin B, fluconazole, itraconazole and
      ketoconazole of 545 Candida strains from patients treated at the University
      Hospital of the Canaries was determined by means of a microdilution test. The
      distribution of the species was as follows: Candida albicans (342), Candida
      tropicalis (70), Candida glabrata (68), Candida parapsilosis (65). Of Candida
      albicans isolates, 8.5% and 7.6% showed resistance to itraconazole and
      fluconazole respectively. Of C. tropicalis isolates 34.3%, 27.1% and 2.9% were
      resistant to itraconazole, fluconazole and ketaconazole respectively. For C.
      glabrata, 10.3% and 4.4% of the isolates under study demonstrated resistance to
      fluconazole and itraconazole respectively. Only 4.6% and 1.5% of C. parapsilosis
      isolates demonstrated resistance to fluconazole and itraconazole respectively. C.
      tropicalis was the most resistant strain and C. parapsilosis the most sensitive.
      The greatest percentages of resistance in vitro were seen with the triazoles.

PMID- 7739662
TI  - Candidosis of the urinary tract with padding phenomenon of the renal pelvises in
      an infant with obstructive uropathy.
AB  - A male infant with obstructive uropathy developed yeast cell agglomerations which
      were detectable macroscopically and by image-generating techniques within both
      renal pelvises after Candida albicans infection of the urinary tract. Therapy
      with flucytosine induced excretion of 'fungal balls' via the urethra.
      Continuation of therapy with liposomal amphotericin B (AmBisome) prevented a
      relapse after development of fungal resistance against flucytosine.
      Sonographically or radiographically detectable formation of 'concrements' within
      the urinary tract of patients with an immature or compromised immune system and
      additional features such as obstructive urinary tract should suggest a localized
      or systemic mycosis, particularly in the context of long-term antibiotic
      treatment.

PMID- 7739663
TI  - Fungitoxic effect of some organic volatile substances against fungi causing
      otomycosis.
AB  - The fungitoxic effect of seven volatile substances (ammonia, carbon disulphide,
      petroleum benzene, carbon dioxide, methanol, glacial acetic acid and hydrogen
      peroxide) against five fungi, i.e. Aspergillus niger, A. flavus, Absidia
      corymbifera, Penicillium nigricans and Candida albicans, was determined on the
      basis of their dry mycelial weight and sporulation or budding activity. These
      organisms were isolated from patients suffering from fungal infections of the
      ear. All the volatile substances tested were found to inhibit mycelial growth and
      sporulation or budding.

PMID- 7739664
TI  - Sequence comparison between the flavoprotein subunit of the fumarate reductase
      (complex II) of the anaerobic parasitic nematode, Ascaris suum and the succinate
      dehydrogenase of the aerobic, free-living nematode, Caenorhabditis elegans.
AB  - Complex II in adult mitochondria of the parasitic nematode, Ascaris suum,
      exhibits high fumarate reductase activity and plays a key role in the anaerobic
      electron-transport observed in these organelles. In the present study, cDNAs for
      the flavoprotein (Fp) subunits of complex II have been isolated, cloned and
      sequenced from both A. suum and the aerobic, free-living nematode, Caenorhabditis
      elegans. Additional sequence at the 3' end of the mRNAs was determined by the
      Rapid Amplification of cDNA Ends (RACE). Nucleotide sequence analysis of the A.
      suum cDNAs revealed a 22-nucleotide trans-spliced leader sequence characteristic
      of many nematode mRNAs, an open reading frame of 1935 nucleotides and a 3'
      untranslated region of 616 nucleotides including a poly (A) tail from a
      polyadenylation signal (AATAAA). The open reading frame encoded a 645 amino acid
      sequence, including a 30 amino acid mitochondrial presequence. The amino acid
      sequences for the Fp subunits from both organisms were very similar, even though
      the ascarid enzyme functions physiologically as a fumarate reductase and the C.
      elegans enzyme a succinate dehydrogenase. The ascarid sequence was much less
      similar to the Escherichia coli fumarate reductase. The sensitivity of other Fp
      subunits to sulfhydryl reagents appears to reside in a cysteine immediately
      preceding a conserved arginine in the putative active site. In both nematode
      sequences, this cysteine is replaced by serine even though the succinate
      dehydrogenase activity of both enzymes is still sensitive to sulfhydryl
      inhibition. A cysteine six residues upstream of the serine may be involved in the
      sulfhydryl sensitivity of the nematode enzymes. Surprisingly, in contrast to
      succinate dehydrogenase activity, the fumarate reductase activity of the ascarid
      enzyme was not sensitive to sulfhydryl inhibition, suggesting that the mechanism
      of the two reactions involves separate catalytic processes.

PMID- 7739665
TI  - In situ detection of Pbs21 mRNA during sexual development of Plasmodium berghei.
AB  - The patterns of expression of ribosomal RNA and mRNA encoding the parasite
      surface antigen Pbs21 have been investigated during the sexual stages of
      development of the malaria parasite, Plasmodium berghei, using the technique of
      non-radioactive in situ RNA hybridisation. An RNA probe complementary to a region
      of the small subunit of P. berghei ribosomal RNA hybridised to parasites at all
      stages of development in a smear of blood taken from mice infected with P.
      berghei. Messenger RNA encoding Pbs21, in contrast, was detected only within
      parasites committed to sexual development within the vertebrate host and,
      furthermore, was shown to be expressed in a sex-specific manner, exclusively
      within female gametocytes. At later stages of sexual development, Pbs21 mRNA was
      detected at high levels in female gametes and ookinetes. We have previously shown
      that Pbs21 protein is first detectable only after the initiation of gametogenesis
      which occurs following transmission to the insect vector. These results suggest,
      therefore, that post-transcriptional mechanisms operate to regulate the
      translation of Pbs21 mRNA as it accumulates during female gametocytogenesis.

PMID- 7739666
TI  - Expression and localization of Trypanosoma cruzi hsp60.
AB  - A 60-kDa heat shock protein (hsp60) is involved in mitochondrial protein folding
      and assembly of oligomeric protein complexes in the mitochondrial matrix. Here we
      report the isolation of Trypanosoma cruzi hsp60 cDNAs, the determination of the
      organization and chromosomal location of the genes, and the assessment of the
      heat-regulated expression and subcellular location of the protein. T. cruzi hsp60
      is encoded by a multigene family organized in two allelic direct tandem arrays on
      a chromosome of 1.6 Mb. The regulation of hsp60 expression by heat is complex.
      While the hsp60 mRNA level is 6-fold higher at 37 degrees C than at either 26
      degrees C, the hsp60 protein level remains essentially constant across all
      temperatures examined. Further analysis of the protein by two-dimensional
      immunoblotting revealed the existence of multiple isoforms that, with increasing
      temperature, shift in relative abundance from the more basic to the more acidic.
      A combination of immunofluorescence microscopy and cell fractionation was used to
      show that hsp60 is distributed throughout the matrix of the mitochondrion--a
      location distinct from that of the 70-kDa mitochondrial hsp, mtp70, which is
      associated with the kinetoplast.

PMID- 7739667
TI  - Enhanced lysosomal acidification leads to increased chloroquine accumulation in
      CHO cells expressing the pfmdr1 gene.
AB  - Expression of the pfmdr1-encoded Pgh1 protein of Plasmodium falciparum in CHO
      cells confers a phenotype of increased sensitivity to chloroquine due to an
      increased Pgh1-mediated accumulation of this antimalarial. Pgh1 carrying amino
      acid substitutions associated with chloroquine resistance in P. falciparum does
      not confer this phenotype. Here, we present studies on the underlying mechanism
      of Pgh1 mediated chloroquine influx into CHO cells. First, we measured
      intralysosomal pH using FITC-labelled dextran and found the intralysosomal pH in
      Pgh1 expressing cells to be decreased. A decreased lysosomal pH was not observed
      in cells expressing Pgh1 carrying the S1034C and N1042D double substitution found
      in some chloroquine-resistant P. falciparum parasites. Secondly, Pgh1-mediated
      uptake of chloroquine was abolished in the presence of bafilomycin A1, a specific
      inhibitor of vacuolar [H+]ATPases and was nearly abrogated in the presence of
      NH4Cl. Finally, cells expressing wild-type Pgh1 showed increased uptake of both
      (+)- and (-)[3H]chloroquine enantiomers, indicating that Pgh1-mediated uptake of
      chloroquine is not enantioselective and in agreement with a pH-driven process. We
      conclude from these studies that Pgh1 does not transport chloroquine, but instead
      influences chloroquine accumulation by modulating the pH of acidic organelles.
      This function is abolished in Pgh1 carrying amino acid substitutions S1034C and
      N1042D. We speculate that the pfmdr1 gene encodes a vacuolar chloride channel.

PMID- 7739668
TI  - A large multigene family expressed during the erythrocytic schizogony of
      Plasmodium falciparum.
AB  - We report the identification of a large multigene family of Plasmodium falciparum
      using a clone isolated with a polyclonal antiserum raised to a Babesia divergens
      merozoite protein. The recombinant antigen reacted with human sera collected from
      individuals exposed to malaria. The deduced protein sequence contains a motif
      homologous to the consensus sequence of merozoite rhoptry proteins encoded by
      multigene families in several Babesia species. Antibodies raised to the
      recombinant protein reacted with a 60-kDa merozoite protein both on B. divergens
      and on P. falciparum immunoblots. The insert hybridized to a large number of
      fragments on P. falciparum Southern blots and to most chromosomes of the
      parasite. Specifically, approx. 3-kb RNAs were detected in 4-16-nucleus
      schizonts. Ten distinct cDNAs were isolated that differed in the size, position
      and number of restriction sites in the region homologous to the original genomic
      clone. With about 140 copies per haploid genome, this is the first large
      multigene family described in malaria parasites. The existence of a multigene
      family encoding proteins present in the invasive stage of malaria parasites
      suggests an important role in invasion and denotes a significant potential for
      generating diversity.

PMID- 7739669
TI  - Sequence and expression of a 90-kilodalton heat-shock protein family member of
      Theileria parva.
AB  - A Theileria parva specific full-length cDNA clone, T7, which encodes a protein
      with more than 60% homology to heat shock protein 90 (hsp90) of other organisms,
      has been identified. T7 appears to be a single copy gene. The gene is expressed
      as a protein of 87 kDa in both the sporozoite and schizont stages of T. parva.
      The protein was not found in the piroplasm stage, although the corresponding
      transcript was detected, suggesting post-transcriptional regulation of the gene.
      In the schizont stage the T7 protein is upregulated upon heat shock and localized
      in the cytoplasm.

PMID- 7739670
TI  - Cloning of a cDNA encoding the dense granule protein GRA3 from Toxoplasma gondii.
AB  - GRA3 is a 30-kDa protein located inside the dense granules of Toxoplasma gondii.
      Following invasion and exocytosis of dense granules within the parasitophorous
      vacuole, GRA3 becomes associated with the parasitophorous vacuolar membrane (PVM)
      and extensions of the PVM which protrude into the cytoplasm. A partial cDNA
      encoding GRA3 was isolated from a Toxoplasma gondii expression library using
      polyclonal and monoclonal antibodies to the mature GRA3 protein of tachyzoites.
      Antibodies affinity purified using the cloned fusion protein reacted with a 30
      kDa band on immunoblots and recognized dense granules, the PVM, and PVM
      extensions by immunofluorescence staining of infected cells. Northern blot
      analysis indicated the major transcript was of a slightly larger size, and the
      complete cDNA encoding GRA3 was subsequently obtained. Southern blot analysis
      suggests that GRA3 is present as a single copy. The cDNA encodes two methionines
      at the N-terminus followed by an open reading frame with a hydrophobic region of
      22 amino acids flanked by charged residues consistent with a signal sequence.
      Four shorter hydrophobic regions occur but are insufficient to span the membrane.
      No significant homology was detected to other proteins, including other dense
      granule proteins. In vitro translation of RNA generated from the cDNA containing
      either one or two of the N-terminal methionines yielded peptides with apparent
      M(r) of 35,000 and 37,000 respectively. Translation of RNA from the cDNA
      containing only the second initiation site in the presence of dog pancreas
      microsomes resulted in reduction of 4 kDa, sufficient to account for removal of
      the putative signal sequence.

PMID- 7739671
TI  - Differential expression in blood stages of the gene coding for the 21-kilodalton
      surface protein of ookinetes of Plasmodium berghei as detected by RNA in situ
      hybridisation.
AB  - The developmentally regulated transcription of the gene encoding the ookinete
      surface protein, Pbs21, has been investigated in the rodent malaria parasite,
      Plasmodium berghei, by RNA in situ hybridisation using fluorescently labelled DNA
      probes. We used a procedure that will allow the visualisation of cytoplasmic mRNA
      in the parasite and of high copy DNA repeats in the nucleus. Specific
      hybridisation to Pbs21 mRNA occurred in the cytoplasm of female gametocytes,
      zygotes and ookinetes, while asexual blood stages, male gametocytes and gametes
      showed no fluorescence. Analysis of the transcription of the Pbs21 gene during
      blood stage development in two tightly synchronised parasite clones using the
      same methodology revealed that transcription is restricted to sexual stages and
      is initiated in immature gametocytes at 19 h post invasion (hpi). At this point
      in development it is not yet possible to discriminate between the morphology of
      asexual trophozoites and immature gametocytes. At 24 hpi approximately 50% of the
      gametocytes transcribed the Pbs21 gene and the morphology of these gametocytes
      was identical and female. The distribution of the mRNA encoding Pbs21 confirmed
      that post-transcriptional control of expression occurred in the cytoplasm by
      repression of translation and not through delayed transport of the message to the
      cytoplasm. The transcription of the Pbs21 gene is the earliest demonstrated event
      in gametocytogenesis in rodent malaria species to date.

PMID- 7739672
TI  - Giardia lamblia trophozoites contain multiple alleles of a variant-specific
      surface protein gene with 105-base pair tandem repeats.
AB  - Giardia lamblia trophozoites undergo antigenic variation of a variant-specific
      surface protein (VSP). All VSPs that have been reported have had high cysteine
      contents, including numerous copies of a CXXC motif. The first vsp gene described
      (vspA6; from the cloned line, WBA6), contained 21 copies of a 195 base pair
      tandem repeat, but other reported VSPs have not contained repeats. In this
      report, we describe the vsp gene from WBC5, a cloned line derived from WBA6. The
      vspC5 gene contains short 5' and 3' regions flanking 26 copies of a 105-bp tandem
      repeat, which comprises 93% of the coding region. In addition to the copy
      containing 26 repeats, the genome contains other copies of the vspC5 with fewer
      copies of the repeat. The sequences flanking the repeats are identical, and all
      copies map to the same location on chromosomal Band 5, suggesting that multiple
      alleles of the vspC5 gene are present.

PMID- 7739673
TI  - The serum resistance-associated (SRA) gene of Trypanosoma brucei rhodesiense
      encodes a variant surface glycoprotein-like protein.
AB  - In the Trypanosoma brucei species, T. b. rhodesiense and T. b. gambiense
      represent the human infective host range variants, while T. b. brucei is lysed
      upon exposure to a cytotoxic factor in normal human serum. T. b. rhodesiense can
      occur in a serum-resistant and a serum-sensitive form. The resistance towards
      normal human serum was shown to be a labile character and to be determined by the
      environment in which the parasites live. We have clearly demonstrated the
      presence of RNA transcripts unique to the resistant forms of T. b. rhodesiense.
      These transcripts encode a protein with VSG characteristics. The DNA fragment
      isolated previously, which hybridises with the resistance-specific mRNA sequence,
      appears to be a pseudogene belonging to the same gene family.

PMID- 7739674
TI  - Conserved location of genes on polymorphic chromosomes of four species of malaria
      parasites.
AB  - The number of chromosomes and the chromosomal location and linkage of more than
      50 probes, mainly of genes, have been established in four species of Plasmodium
      which infect African murine rodents. We expected that the location and linkage of
      genes would not be conserved between these species of malaria parasites since
      extensive inter- and intraspecific size differences of the chromosomes existed
      and large scale internal rearrangements and chromosome translocations in
      parasites from laboratory lines had been reported. Our study showed that all four
      species contained 14 chromosomes, ranging in size between 0.5 and 3.5 Mb, which
      showed extensive size polymorphisms. The location and linkage of the genes on the
      polymorphic chromosomes, however, was conserved and nearly identical between
      these species. These results indicate that size polymorphisms of the chromosomes
      are more likely due to variation in non-coding (subtelomeric, repeat) sequences
      and show that a high plasticity of internal regions of chromosomes that may exist
      does not frequently affect chromosomal location and linkage of genes.

PMID- 7739676
TI  - Genetic diversity of Schistosoma mansoni: quantifying strain heterogeneity using
      a polymorphic DNA element.
AB  - Intraspecific genetic variation among 14 geographic isolates of Schistosoma
      mansoni was quantified using a molecular marker to examine individual genotypes.
      Genetic crosses demonstrated maternal inheritance of S. mansoni DNA element
      pSM750. This element revealed diagnostic banding profiles, which allowed accurate
      strain identification. Most strains had similarity indices greater than 0.75
      indicating that within-strain variation in these laboratory parasite populations
      was low. However, individual parasites from the NMRI strain were quite diverse (S
      = 0.40). Genetic heterogeneity among strains was quantified using a phenogram of
      mean genetic distance. Strain diversity between two geographic regions was
      quantified using a similarity index and was estimated to be substantial among
      isolates collected from a single local site.

PMID- 7739675
TI  - Developmental regulation of RNA editing and polyadenylation in four life cycle
      stages of Trypanosoma congolense.
AB  - The accumulation of many edited mRNAs is developmentally regulated in a
      transcript-specific fashion in Trypanosoma brucei. In addition, these transcripts
      are frequently present in two size classes which differ substantially in the
      lengths of their poly(A) tails, and poly(A) tail length is also developmentally
      regulated. Previously, these phenomena have only been studied in the mammalian
      bloodstream and insect procyclic forms (BF and PF, respectively) of T. brucei. In
      this paper, we examine developmental regulation of edited RNA abundance and
      poly(A) tail length of 3 mitochondrially encoded RNAs in mammalian BF and 3
      insect stages (PF, epimastigotes, and metacyclics) of T. congolense. T.
      congolense BF and PF are similar, but not identical, to these stages of T. brucei
      with regard to edited RNA accumulation and poly(A) tail length. At the level of
      edited RNA, both epimastigotes and metacyclic stage parasites appear to be pre
      adapted for the respiratory mechanisms of BF but not yet down-regulated from the
      cytochrome-based respiration of PF since edited RNAs encoding NADH dehydrogenase
      components are up-regulated and edited CYb RNA is abundant in these stages.
      Poly(A) tail lengths of mitochondrial mRNAs appear to be regulated independently
      of edited RNA abundance. These results indicate that multiple mechanisms for
      regulation of mitochondrial gene expression are active throughout the trypanosome
      life cycle.

PMID- 7739677
TI  - Characterisation of the carbamoyl phosphate synthetase gene from Plasmodium
      falciparum.

PMID- 7739678
TI  - The Schistosoma mansoni phosphagen kinase gene contains two closely apposed
      transcription initiation sites and arose from a fused gene duplication.

PMID- 7739679
TI  - Primary structure of an Entamoeba histolytica nicotinamide nucleotide
      transhydrogenase.

PMID- 7739680
TI  - A simple method for typing Plasmodium falciparum merozoite surface antigens 1 and
      2 (MSA-1 and MSA-2) using a dimorphic-form specific polymerase chain reaction.

PMID- 7739681
TI  - A comparison of three interferon alfa-2b regimens for the long-term treatment of
      chronic non-A, non-B hepatitis. Multicenter Study Group.
AB  - BACKGROUND: We studied the effects of long-term treatment with interferon on
      histologic features of the liver and serum alanine aminotransferase
      concentrations in patients with chronic non-A, non-B hepatitis. METHODS:
      Consecutive patients who met the inclusion criteria were enrolled in the study.
      The diagnosis of chronic non-A, non-B hepatitis was established on the basis of
      the liver-biopsy findings and an abnormal serum alanine aminotransferase value
      (greater than 1.5 times the normal value) for at least one year. All patients
      were treated for six months with 3 million units of interferon alfa-2b given
      subcutaneously three times a week and were then randomly assigned to the same
      treatment for an additional 12 months (group 1), a regimen of 1 million units
      three times a week for 12 months (group 2), or no further treatment (group 3).
      Patients in group 3 who had elevated serum alanine aminotransferase
      concentrations for three consecutive months underwent the initial regimen once
      again. Follow-up continued for two years after the discontinuation of treatment.
      Histologic improvement was defined as a decrease of at least one grade in the
      score for necroinflammatory activity (0, no activity; 1, mild; 2, moderate; or 3,
      severe) between the first liver biopsy and a biopsy performed at 18 months.
      RESULTS: Of the 329 patients initially treated, 303 were randomized: 103 to group
      1, 101 to group 2, and 99 to group 3. Of the 286 patients tested, 252 (88.1
      percent) had antibodies to hepatitis C virus. In an intention-to-treat analysis,
      46 of the patients in group 1 (44.7 percent) had normal serum alanine
      aminotransferase values at 18 months, as compared with 27 of the patients in
      group 2 (26.7 percent, P = 0.008) and 30 of those in group 3 (30.3 percent, P =
      0.04). Between 19 and 42 months, 23 of the patients in group 1 (22.3 percent)
      continued to have normal serum alanine aminotransferase values (measured every
      six months), as compared with 10 of the patients in group 2 (9.9 percent, P =
      0.02) and 8 of those in group 3 (8.1 percent, P = 0.005). Among the 176 patients
      with repeated liver biopsies at 18 months, more patients in group 1 had improved
      histologic-activity scores (69.6 percent) than in group 2 (47.6 percent, P =
      0.02) or group 3 (38.6 percent, P < 0.001). CONCLUSIONS: Among patients with
      chronic non-A, non-B hepatitis, a regimen of 3 million units of interferon alfa
      2b given three times a week for 18 months produced better histologic findings and
      serum alanine aminotransferase values than regimens involving a lower dose or a
      shorter duration of treatment.

PMID- 7739682
TI  - Clinical outcomes after transfusion-associated hepatitis C.
AB  - BACKGROUND: The extent of serious complications in people who have acquired
      chronic hepatitis C infection after a blood transfusion is unclear. METHODS: We
      studied 131 patients with chronic post-transfusion hepatitis C who were referred
      to our center between February 1980 and June 1994. Eighty-two other patients were
      excluded because they had multiple transfusions, hemophilia, intravenous drug
      use, human immunodeficiency virus infection, hepatitis B infection,
      hemochromatosis, or alcoholic liver disease. Liver biopsies were performed in 101
      patients; biopsies were not performed in the other 30 patients, all with signs of
      cirrhosis, because the results of coagulation tests were abnormal. RESULTS: The
      mean age of the patients was 57 years (range, 21 to 81) at the time of our
      initial evaluation. The mean age at the time of the blood transfusion was 35
      years (range, 1 to 76). The mean duration of follow-up after presentation to us
      was 3.9 years (range, 1 to 15). Eighty-eight of the patients (67.2 percent)
      initially had fatigue, and 89 (67.9 percent) had hepatomegaly. Twenty-seven
      patients (20.6 percent) initially had chronic hepatitis, 30 (22.9 percent) had
      chronic active hepatitis, 67 (51.1 percent) had cirrhosis, and 7 (5.3 percent)
      had hepatocellular carcinoma. Hepatocellular carcinoma developed in an additional
      seven patients an average of 36 months (range, 7 to 121) after the initial visit.
      During follow-up, 20 patients (15.3 percent) died: 8 from complications of
      cirrhosis (1 after a liver transplantation); 11 from hepatocellular carcinoma;
      and 1, with chronic active hepatitis, from pneumonia. CONCLUSIONS: In a group of
      patients seen at a referral center, chronic post-transfusion hepatitis C was a
      progressive disease and, in some patients, led to death from either liver failure
      or hepatocellular carcinoma.

PMID- 7739683
TI  - Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic
      syndromes.
AB  - BACKGROUND: Voltage-gated calcium channels in small-cell lung carcinomas may
      initiate autoimmunity in the paraneoplastic neuromuscular disorder Lambert-Eaton
      syndrome. The calcium-channel subtype that is responsible is not known. METHODS:
      We compared the effects of antagonists of L-type, N-type, and P/Q-type neuronal
      calcium channels on the depolarization-dependent influx of calcium-45 in cultured
      carcinoma cells. Serum samples from patients with various disorders were tested
      for reactivity with P/Q-type channels solubilized from carcinoma and cerebellar
      membranes and N-type channels from cerebral cortex. RESULTS: P/Q-type calcium
      channel antagonists were the most potent inhibitors of depolarization-induced
      45Ca influx in cultured small-cell carcinoma cell lines. Anti-P/Q-type calcium
      channel antibodies were found in serum from all 32 patients with Lambert-Eaton
      syndrome and a diagnosis of cancer and in 91 percent of the 33 patients with
      Lambert-Eaton syndrome without cancer. Anti-N-type calcium-channel antibodies
      were found in 49 percent of the 65 patients with the Lambert-Eaton Syndrome.
      Lower titers of anti-P/Q-type and anti-N-type calcium-channel antibodies were
      found in 54 percent of 70 patients with a paraneoplastic
      encephalomyeloneuropathic complication of lung, ovarian, or breast carcinoma, 24
      percent of 90 patients with cancer but no evident neurologic complications, 23
      percent of 78 patients with sporadic amyotrophic lateral sclerosis, and less than
      3 percent of 69 patients with myasthenia gravis, epilepsy, or scleroderma.
      CONCLUSIONS: The high frequency of P/Q-type calcium-channel antibodies found in
      patients with Lambert-Eaton syndrome implies that antibodies of this specificity
      have a role in the presynaptic pathophysiology of this disorder.

PMID- 7739684
TI  - Mutations in the cystic fibrosis gene in patients with congenital absence of the
      vas deferens.
AB  - BACKGROUND: Congenital bilateral absence of the vas deferens (CBAVD) is a form of
      male infertility in which mutations in the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene have been identified. The molecular basis of
      CBAVD is not completely understood. Although patients with cystic fibrosis have
      mutations in both copies of the CFTR gene, most patients with CBAVD have
      mutations in only one copy of the gene. METHODS: To investigate CBAVD at the
      molecular level, we have characterized the mutations in the CFTR gene in 102
      patients with this condition. None had clinical manifestations of cystic
      fibrosis. We also analyzed a DNA variant (the 5T allele) in a noncoding region of
      CFTR that causes reduced levels of the normal CFTR protein. Parents of patients
      with cystic fibrosis, patients with types of infertility other than CBAVD, and
      normal subjects were studied as controls. RESULTS: Nineteen of the 102 patients
      with CBAVD had mutations in both copies of the CFTR gene, and none of them had
      the 5T allele. Fifty-four patients had a mutation in one copy of CFTR, and 34 of
      them (63 percent) had the 5T allele in the other CFTR gene. In 29 patients no
      CFTR mutations were found, but 7 of them (24 percent) had the 5T allele. In
      contrast, the frequency of this allele in the general population was about 5
      percent. CONCLUSIONS: Most patients with CBAVD have mutations in the CFTR gene.
      The combination of the 5T allele in one copy of the CFTR gene with a cystic
      fibrosis mutation in the other copy is the most common cause of CBAVD: The 5T
      allele mutation has a wide range of clinical presentations, occurring in patients
      with CBAVD or moderate forms of cystic fibrosis and in fertile men.

PMID- 7739685
TI  - Images in clinical medicine. Tension pneumopericardium.

PMID- 7739686
TI  - Chronic pancreatitis.

PMID- 7739687
TI  - Management of primary hyperlipidemia.

PMID- 7739688
TI  - Molecular diagnosis (2)

PMID- 7739689
TI  - Clinical problem-solving. Costly errors.

PMID- 7739690
TI  - Teaching problem-solving--how are we doing?

PMID- 7739691
TI  - Interferon and hepatitis C.

PMID- 7739692
TI  - A promising animal model of Alzheimer's disease.

PMID- 7739693
TI  - Kidney failure and analgesic drugs.

PMID- 7739694
TI  - Kidney failure and analgesic drugs.

PMID- 7739695
TI  - Spreading cerebral hypoperfusion during migraine headache.

PMID- 7739696
TI  - Spreading cerebral hypoperfusion during migraine headache.

PMID- 7739697
TI  - Spreading cerebral hypoperfusion during migraine headache.

PMID- 7739698
TI  - Spreading cerebral hypoperfusion during migraine headache.

PMID- 7739699
TI  - Gastrointestinal polyposis and nonpolyposis syndromes.

PMID- 7739700
TI  - Gastrointestinal polyposis and nonpolyposis syndromes.

PMID- 7739701
TI  - Gastrointestinal polyposis and nonpolyposis syndromes.

PMID- 7739702
TI  - Gastrointestinal polyposis and nonpolyposis syndromes.

PMID- 7739703
TI  - Isotretinoin for juvenile chronic myelogenous leukemia.

PMID- 7739704
TI  - Isotretinoin for juvenile chronic myelogenous leukemia.

PMID- 7739705
TI  - p53 antigen loss in stored paraffin slides.

PMID- 7739706
TI  - Fluoxetine in the treatment of premenstrual dysphoria. Canadian
      Fluoxetine/Premenstrual Dysphoria Collaborative Study Group.
AB  - BACKGROUND: Premenstrual dysphoria shares certain features with depression and
      anxiety states, which have been linked to serotonergic dysregulation. We
      evaluated the efficacy and safety of fluoxetine (which selectively inhibits the
      reuptake of serotonin) in the treatment of premenstrual dysphoria. METHODS: The
      trial consisted of a single-blind, placebo washout period lasting two menstrual
      cycles, followed by a randomized, double-blind, placebo-controlled trial of
      fluoxetine at a dose of either 20 mg or 60 mg per day or placebo for six
      menstrual cycles. Healthy women meeting criteria for what was then called late
      luteal-phase dysphoric disorder were recruited at seven university-affiliated
      women's health clinics in Canada. The primary outcome measure consisted of visual
      analogue scales for tension, irritability, and dysphoria during the late luteal
      phase of each cycle. RESULTS: Of 405 women enrolled in the placebo washout
      period, 313 subsequently entered the randomized phase of the study, which lasted
      six menstrual cycles, and 180 completed it. Fluoxetine at a dose of 20 or 60 mg
      per day was significantly superior to placebo in reducing symptoms of tension,
      irritability, and dysphoria, as measured by the visual-analogue scales (P <
      0.001). The women who received 60 mg of fluoxetine per day reported significantly
      more side effects than those who received 20 mg per day or placebo (P < 0.001).
      CONCLUSIONS: Fluoxetine is useful in the treatment of premenstrual dysphoria.
      Treatment with fluoxetine at a dose of 20 mg per day reduces the potential for
      side effects while maximizing therapeutic efficacy.

PMID- 7739707
TI  - Breast implants and breast cancer--reanalysis of a linkage study.
AB  - BACKGROUND: In 1992, Berkel and colleagues reported in the Journal the results of
      their study of the potential association of breast augmentation and breast
      cancer. The study reported that women who had breast augmentation had a
      significantly lower subsequent risk of breast cancer (P < 0.01) than the general
      population, with a standardized incidence ratio of 0.48 overall. Assuming a 10
      year induction period (that is, assuming that cancers found within 10 years of
      the augmentation might have been the result of a process begun before surgery and
      therefore should not be considered), the reported standardized incidence ratio
      was 0.16. Problems were later identified involving some of the study methods.
      This paper reports a second analysis of these data. METHODS: We used a data set
      from Alberta Health Care to identify eligible women with bilateral breast
      augmentation. Using a combination of deterministic and probabilistic methods, we
      linked this data set to the Alberta Cancer Registry to identify subsequent breast
      cancers that developed during the study period. Multiple estimates of
      standardized incidence ratios were calculated on the basis of differing study
      eligibility dates, induction periods, and types of breast-cancer (invasive only
      or invasive plus in situ). RESULTS: The reanalysis found substantial differences
      in the numbers of person-years at risk, resulting in higher standardized
      incidence ratios than in the original analysis. The final ratios for all breast
      cancers, with October 1, 1973, used as the starting date of the study, were 0.76
      (95 percent confidence interval, 0.55 to 1.02), 0.85 (95 percent confidence
      interval, 0.58 to 1.19), and 0.68 (95 percent confidence interval, 0.32 to 1.25)
      for induction periods of 0, 5, and 10 years, respectively. None of these
      standardized incidence ratios were significantly different from 1. CONCLUSIONS:
      On the basis of this reanalysis, the incidence of breast cancer among the women
      who had breast augmentation could not be said to be either significantly higher
      or lower than that among the general population over the period during which this
      cohort was followed.

PMID- 7739708
TI  - Increased expression of the c-fos proto-oncogene in bone from patients with
      fibrous dysplasia.
AB  - BACKGROUND: Fibrous dysplasia is characterized by intense marrow fibrosis and
      increased rates of bone turnover. The lesions of fibrous dysplasia resemble those
      described in the long bones of transgenic mice overexpressing the c-fos proto
      oncogene. Activating mutations in the alpha subunit of the stimulatory guanine
      nucleotide-binding protein (GS alpha) linked to adenylate cyclase have recently
      been described in bone cells from patients with the McCune-Albright syndrome and
      fibrous dysplasia. METHODS: We used in situ hybridization to determine the level
      of expression of c-fos in bone-biopsy specimens from two normal subjects, eight
      patients with fibrous dysplasia, and six patients with other bone disorders
      characterized by high rates of bone turnover. The probe used corresponded to the
      fourth exon of the c-fos gene. RESULTS: High levels of c-fos expression were
      detected in the bone lesions from all eight patients with fibrous dysplasia. No
      expression of c-fos was detected in bone specimens from the normal subjects or
      from specimens of normal bone obtained from patients with fibrous dysplasia. The
      cells that expressed c-fos in the dysplastic lesions were fibroblastic and
      populated the marrow space. A very low level of c-fos expression was detected in
      the biopsy specimens from the patients with other bone diseases. One patient with
      polyostotic fibrous dysplasia and one patient with the McCune-Albright syndrome
      were tested for the previously described GS alpha gene mutations and were found
      to express these mutations in bone. CONCLUSIONS: Increased expression of the c
      fos proto-oncogene, presumably a consequence of increased adenylate cyclase
      activity, may be important in the pathogenesis of the bone lesions in patients
      with fibrous dysplasia.

PMID- 7739709
TI  - Images in clinical medicine. Coining.

PMID- 7739710
TI  - Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine.

PMID- 7739711
TI  - Otitis media in children.

PMID- 7739712
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 17-1995. An 81-year-old woman with mitral regurgitation and a
      left-upper-lobe pulmonary infiltrate.

PMID- 7739713
TI  - The treatment of premenstrual syndrome--forward into the past.

PMID- 7739714
TI  - Signaling pathways and c-fos transcriptional response--links to inherited
      diseases.

PMID- 7739715
TI  - Family history and colorectal cancer.

PMID- 7739716
TI  - Family history and colorectal cancer.

PMID- 7739717
TI  - Complications and failures of subclavian-vein catheterization.

PMID- 7739718
TI  - Complications and failures of subclavian-vein catheterization.

PMID- 7739719
TI  - Complications and failures of subclavian-vein catheterization.

PMID- 7739720
TI  - Complications and failures of subclavian-vein catheterization.

PMID- 7739721
TI  - Hydrocolonic ultrasonography.

PMID- 7739722
TI  - Wandering patients in the Veterans Affairs system.

PMID- 7739723
TI  - Wandering patients in the Veterans Affairs system.

PMID- 7739724
TI  - Severe necrotizing cutaneous lesions complicating treatment with interferon beta
      1b.

PMID- 7739725
TI  - Roller-coaster headache.

PMID- 7739726
TI  - Discrepancies between MIC and MLC values of amphotericin B against isolates of
      Aspergillus species.
AB  - There is little information addressing the phenomena of discrepancy between
      minimal inhibitory concentrations (MIC) and minimal lethal concentrations (MLC)
      values of amphotericin B (AMB) to clinical isolates of fungi. This study assessed
      in vitro activity of AMB against 70 clinical isolates of aspergilli: 30 strains
      of Aspergillus fumigatus, 20 strains of Aspergillus flavus and 20 strains of
      Aspergillus niger. Susceptibility tests were accomplished using a macro broth
      dilution procedure, with special emphasis on ascertainment of MLCs. AMB exhibited
      low MIC values against all clinical isolates. While we did not identify any AMB
      resistant isolates among 70 Aspergillus spp. studied as judged by MIC levels,
      analysis of the data demonstrated a clear discrepancy between the MIC and MLC
      levels of AMB obtained against clinical isolates of Aspergillus spp. The MLC
      values of AMB were significantly higher than the MIC values with MIC 50 and MIC
      90 of 0.29 and 0.5 microgram/ml, respectively, at the second reading time, and
      MLC 50 and MLC 90 of 2.31 and 9.24 micrograms/ml, respectively (p < 0.001).
      Additionally, minimal lethal concentrations in 36/70 (51%) of aspergillal
      isolates studied produced drug concentrations above those which can usually be
      sustained in patient plasma or tissue.

PMID- 7739727
TI  - In vitro susceptibility to 9 antifungal agents of 14 strains of Zygomycetes
      isolated from clinical specimens.
AB  - Fourteen clinical isolates of Zygomycetes were tested for their in vitro
      susceptibility to nine antifungal agents. Susceptibility assessment was performed
      using a microtiter broth dilution method. Synthetic broth with YNB and glucose
      was used for 5-fluorocytosine and BHI broth for all the other antimycotics.
      Amphotericin B exhibited the strongest activity against all isolates tested. MIC
      values of other two polyenes--nystatin and pimaricin--ranged within the
      susceptibility limits, with a little pronounced higher activity of pimaricin. The
      isolates of the genus Absidia and Syncephalastrum were well sensitive to all
      antimycotics with the exception of 5-fluorocytosine and naftifine. A very weak or
      zero growth inhibitory effect against all members of the genera Mucor and
      Rhizopus was found in azoles, 5-fluorocytosine and naftifine.

PMID- 7739728
TI  - Extracellular proteolytic activity of Cryptococcus neoformans.
AB  - Eight strains of Cryptococcus neoformans var. neoformans isolated from AIDS
      patients in the Infectious Disease Institute, University of Turin, Italy, were
      examined for growth and extracellular proteolytic activity in culture with solid
      and liquid media. All of the strains grew well on Yeast Carbon Base (YCB) agar
      medium supplemented with both 0.1% (w/v) bovine serum albumin (BSA) and 0.01%
      (w/v) polypeptone (Pp), and produced a clear proteolytic zone around their
      colonies, whereas they exhibited less growth and proteolytic activity on YCB
      medium supplemented with BSA alone. Strain #8 with a strong proteolytic activity
      was cultured in three different liquid media. Its growth was limited in YCB
      medium supplemented with 0.1% BSA, but was moderate in that with 0.01% Pp.
      Enhanced growth was supported by the addition of both BSA and Pp to the YCB
      medium. The relative value of the final cellular yields obtained with the above
      YCB-0.1% BSA, YCB-0.01% Pp and YCB-0.1% BSA-0.01% Pp media was approximately
      1:10:20. In the culture with YCB medium containing both BSA and Pp, a rapid
      decrease in the amount of BSA was demonstrated by a spectrophotometric assay and
      gel electrophoresis of the culture supernatant after the log-to-stationary phase.
      The proteolytic activity in the culture supernatant became detectable after the
      log phase when tested with skim milk agarose plates. These results allowed us to
      conclude that Cr. neoformans var. neoformans is able to secrete protease and to
      utilize protein as a source of nitrogen.

PMID- 7739729
TI  - Antifungal properties of essential oils and their main components upon
      Cryptococcus neoformans.
AB  - Cryptococcus neoformans opportunistic fungus met in the last phasis of AIDS is
      inhibited in vitro by several essential oils on natural volatile compounds. The
      minimal inhibitory concentration may reach 100 microliters/l and minimal
      fungicidal concentration 200 microliters/l with Palmarosa or Cinnamon oils. Among
      phenolic compounds, thymol and carvacrol are most fungitoxic. Terpenoids, citral,
      geraniol, and citronellol show best activities.

PMID- 7739731
TI  - [Upper abdominal pain in the second half of pregnancy: HELLP].

PMID- 7739730
TI  - Cytotoxicity of mycotoxins evaluated by the MTT-cell culture assay.
AB  - The application of a modified colorimetric bioassay for the evaluation of the
      biological effects of mycotoxins is reported. Using three different monolayer
      cell lines (swine kidney, Madin Darby canine kidney, HeLa) the influence of nine
      different mycotoxins on the cellular methylthiazoltetrazolium (MTT)-cleavage
      activity was evaluated. The yellow tetrazolium salt MTT is converted by
      mitochondrial dehydrogenases of metabolically active cells to an insoluble purple
      formazan product, which was then solubilized with dimethylsulfoxide. The optical
      density of this homogeneous solution was suitable for a precise
      spectrophotometric measurement by a plate reader at a wavelength of 510 nm. Nine
      mycotoxins were simultaneously tested in all three cell lines, from which the
      swine kidney cell line proved to be the most sensitive. The effects of additional
      35 mycotoxins were therefore tested using swine kidney monolayers as target
      cells. A total of 28 toxins of the 44 mycotoxins tested proved to be cytotoxic in
      the MTT-bioassay. Most of them belong to the group of trichothecene mycotoxins.
      Concentrations ranged between 0.01 micrograms and 100 micrograms/ml of cell
      culture medium. The MTT cleavage assay was found to be a quick (24 hours) and
      easy to perform system for the evaluation of the biological activity of many
      different mycotoxins and may also provide a useful tool for the testing of a
      large variety of sample materials.

PMID- 7739732
TI  - [Assisted suicide].

PMID- 7739733
TI  - [Drugs and the aged: feasibility of the Health Council recommendations].

PMID- 7739734
TI  - [Familial forms of fronto-temporal dementia].

PMID- 7739735
TI  - [Vitamin K: current viewpoints in connection with bone metabolism].

PMID- 7739736
TI  - [Absence of meningitis caused by Haemophilus influenzae type b in The Netherlands
      following twofold vaccination].
AB  - OBJECTIVE: To determine the two-year results of nationwide vaccination with
      Haemophilus influenzae type b (Hib) vaccine on the occurrence of Hib meningitis
      in the Netherlands. DESIGN: Retrospective controlled study. SETTING: The
      Netherlands. METHOD: Children born since April 1, 1993 are vaccinated at the age
      of 3, 4, 5 and 11 months to protect them from infections with Hib. The number of
      Hib meningitis patients in the period 1 April, 1993 to 1 April, 1995, among
      infants born in this period who were offered the Hib vaccine (study group), was
      compared with the number of Hib meningitis patients in the period 1 April, 1991
      to 1 April, 1993 among children born in last-mentioned period (control group).
      RESULTS: Twenty-one cases of meningitis by Hib were observed in the study group.
      Twelve children who, as a consequence of their age, had only been vaccinated once
      or not at all; 7 children were not vaccinated for several reasons. In addition
      one patient was infected by H. influenzae type f strain and one by a non-typable
      strain. In the control group 185 cases of Hib meningitis occurred. CONCLUSION:
      Hib meningitis was not observed among infants who had been vaccinated at least
      twice.

PMID- 7739737
TI  - [Pediatric surveillance of invasive infections caused by Haemophilus influenzae
      type b in children in the period following introduction of vaccination].
AB  - OBJECTIVE: Evaluation of the effect of vaccination against Haemophilus influenzae
      type b (Hib) on the occurrence of invasive Hib infections in children since its
      introduction into the national immunization programme in April 1993. DESIGN:
      Observational study. SETTING: Nationwide investigation. METHOD: Data collected
      through active surveillance of invasive Hib infections by paediatricians for the
      period from October 1993 to September 1994 (11 months) were compared with data
      from the meningitis surveillance by the Netherlands Reference Laboratory for
      Bacterial Meningitis. RESULTS: A total of 139 paediatric reports of invasive
      disease by H. influenzae concerned 57 cases of only meningitis, 35 of meningitis
      with sepsis, 2 of meningitis with arthritis, one of meningitis with arthritis and
      osteomyelitis, 34 of epiglottitis including one case with sepsis, 8 of only
      sepsis and 2 of only arthritis. All proven infections by Hib occurred in children
      who had not or incompletely been vaccinated. One child with sepsis had had three
      vaccinations and became ill five months later; the isolated bacterial strain was
      not serotyped. Typing was performed in only 80% of the isolates, of which 98%
      were of type b. Appropriate culturing and typing was often omitted in case of
      epiglottitis. CONCLUSION: The effect of vaccination against Hib became apparent
      in a small number of cases of invasive Hib disease reported by paediatricians;
      the peak incidence of meningitis no longer occurred in children under one year of
      age but in children aged one year. The paediatric surveillance described offers
      possibilities for monitoring Hib epidemiology.

PMID- 7739738
TI  - [Patient characteristics with predictive significance for 'blocked bed' problems
      in the neurological department of a general hospital].
AB  - OBJECTIVE: To determine the extent and the prognostic patient characteristics of
      bed-blocking (hospital beds occupied by patients who no longer need specialist
      medical treatment) in the neurological ward of a general hospital. DESIGN:
      Prospective cohort study. SETTING: Maasland hospital Sittard-Geleen (location
      Sittard). METHOD: During one year each patient of the complete patient population
      of two neurological wards was registered relating to: main diagnosis, age, sex,
      living situation, lesion localisation (only for cerebrovascular accident (CVA)
      patients) and bed-blocking. The predictive patient characteristics for bed
      blocking were determined by logistic regression analysis. RESULTS: 1088 patients
      were registered, of whom 21% with a CVA. In 10% of the registered patients bed
      blocking occurred, 86% of these had the diagnosis of CVA. Of all CVA patients 40%
      became bed-blockers. Of all nursing days of CVA patients 20% were bed-blocking
      days. Among the CVA patients sex (female), age (> or = 70), and the localisation
      of the lesion were found to be significant risk factors for bed-blocking. The
      main patient characteristics predictive for bed-blocking were the diagnosis of
      CVA and age > or = 70 years. CONCLUSION: Neurological patients with an increased
      risk to end up in a blocked bed are mainly found among CVA patients. Since 20% of
      the nursing days of CVA patients were bed-blocking days, shortening of
      hospitalization time and improvement of home care is recommended.

PMID- 7739739
TI  - [From the library of the Nederlands Tijdschrift voor Geneeskunde: Jacques
      Guillemeau's '113 eye diseases'].

PMID- 7739740
TI  - [Hypertension diagnosis by the family physician: measurements according to the
      NHG-standard (Dutch College of Family Physicians) compared to ambulatory blood
      pressure determination].

PMID- 7739741
TI  - [Hypertension diagnosis by the family physician: measurements according to the
      NHG standard (Dutch College of Family Physicians) compared to ambulatory blood
      pressure determination].

PMID- 7739742
TI  - [Epidemiology of celiac disease in The Netherlands].

PMID- 7739743
TI  - [Work disability cause by airway diseases in employees of a mixed feed plant:
      notifiable as an occupational disease?].

PMID- 7739744
TI  - [Oral treatment of onychomycosis of the toe nails; comparison of cost
      effectiveness of griseofulvin, itraconazole, ketoconazole and terbinafine].

PMID- 7739745
TI  - The bottleneck of attention: connecting thought with motivation.

PMID- 7739746
TI  - Social intelligence and intelligent goal pursuit: a cognitive slice of
      motivation.

PMID- 7739747
TI  - A motivational theory of psychopathology.

PMID- 7739748
TI  - Domains of behavior from a neuropsychological perspective: the whole story.

PMID- 7739749
TI  - Environmental control of goal-directed action: automatic and strategic
      contingencies between situations and behavior.

PMID- 7739750
TI  - Neurite outgrowth in PC12 cells stimulated by acetyl-L-carnitine arginine amide.
AB  - Senescence of the central nervous system is characterized by a progressive loss
      of neurons that can result in physiological and behavioral impairments. Reduction
      in the levels of central neurotrophic factors or of neurotrophin receptors may be
      one of the causes of the onset of these degenerative events. Thus, a proper
      therapeutic approach would be to increase support to degenerating neurons with
      trophic factors or to stimulate endogenous neurotrophic activity. Here we report
      that acetyl-L-carnitine arginine amide (ST-857) is able to stimulate neurite
      outgrowth in rat pheochromocytoma PC12 cells in a manner similar to that elicited
      by nerve growth factor (NGF). Neurite induction by ST-857 requires de novo mRNA
      synthesis and is independent of the action of several common trophic factors. The
      integrity of the molecular structure of ST-857 is essential for its activity, as
      the single moieties of the molecule have no effect on PC12 cells, whether they
      are tested separately or together. Also, minor chemical modifications of ST-857,
      such as the presence of the arginine moiety at a position other than the amino
      one, completely abolish its neuritogenic effect. Lastly, the presence of ST-857
      in the culture medium competes with the high affinity NGF binding in a dose
      dependent fashion. These results, although preliminary, are suggestive of a
      possible role for ST-857 in the development of therapeutic strategies to
      counteract degenerative diseases of the CNS.

PMID- 7739751
TI  - Effects of repeated injection of cyclosporin A on pentylenetetrazol-induced
      convulsion and cyclophilin mRNA levels in rat brain.
AB  - To investigate the relationship between the immune system and convulsions in an
      animal model, we examined the effects of repeated administration with the
      immunosuppressant cyclosporin A on pentylenetetrazol (PTZ)-induced convulsions
      and the changes in the mRNA expression of its binding protein cyclophilin in the
      rat brain. The consecutive administration of cyclosporin A (5 mg/kg, s.c., 14
      days) significantly aggravated the severity of convulsions induced with PTZ 75
      mg/kg, i.p. Furthermore, it down-regulated the levels of cyclophilin mRNA in
      several brain regions and inhibited the PTZ-induced increase of hippocampal
      cyclophilin mRNA. Compared with the group without PTZ pretreatment or the group
      treated with chronic vehicle administration after the PTZ-preinjection, chronic
      cyclosporin A administration after the initial injection of PTZ apparently
      aggravated convulsions after the second PTZ injection. Interestingly, the
      increase in hippocampal cyclophilin mRNA observed after a single PTZ injection
      was not found after the second PTZ injection in the group with PTZ pretreatment.
      Therefore, these findings suggest that cyclosporin A administered peripherally
      can affect the central nervous system, and that an immune response associated
      with the first convulsive episode plays a key role in severity during subsequent
      attacks.

PMID- 7739752
TI  - Cloning, expression, and tissue distribution of a fifth melanocortin receptor
      subtype.
AB  - The melanocortin (MC) peptides mediate a diverse spectrum of biological
      activities in both the central nervous system and peripheral tissues by
      interacting with specific guanine nucleotide binding (G protein)-coupled
      receptors. Previously, four human melanocortin receptor subtypes have been cloned
      and characterized. In this study, we have isolated mouse complementary DNA (cDNA)
      and human genomic clones encoding a fifth melanocortin receptor subtype, MC5.
      Melanocortin peptide stimulation of human MC5, transiently expressed in COS1
      cells, results in activation of adenylate cyclase with the following rank order
      of potency: [Nle4, D-Phe7]-alpha-MSH (melanocyte stimulating hormone) > ACTH (1
      24) (adrenocorticotropic hormone) > alpha-MSH > beta-MSH > gamma-MSH. Northern
      blot hybridization, ribonuclease protection, and reverse transcription/polymerase
      chain reaction assays indicate that mouse MC5 mRNA is most abundant in skeletal
      muscle and brain. Lower but detectable levels of MC5 mRNA are also found in RT2-2
      retinal neuronal cells, lung, testis, spleen, heart, kidney, and liver.

PMID- 7739753
TI  - 70-kDa heat shock protein expression in cultured rat astrocytes after hypoxia:
      regulatory effect of almitrine.
AB  - Induction of heat shock proteins (Hsps), especially the 70-kDa family, is well
      observed in nervous tissues in response to various stressful conditions. By using
      rat astrocytes in primary culture, the expression of the inducible (Hsp70) and
      the constitutive (Hsc70) 70-kDa Hsps immunoreactivity of cells exposed to hypoxic
      conditions has been investigated. We observed that exposure of astroglial cells
      to an hypoxic-normoxic sequence induces a significant decrease of Hsc70
      immunoreactivity. The presence of the heat inducible stress protein Hsp70 is
      never observed in hypoxic cells nor in control. Hsc 70 lowering is associated
      with ultrastructural alterations characterized by mitochondria swelling,
      formation of vacuoles and accumulation of dense material in the cell cytoplasm.
      The effects of addition of almitrine to the culture medium before and during
      hypoxia on Hsps immunoreactivity have been examined. The presence of the drug
      prevents the decrease of Hsc70 immunoreactivity induced by hypoxia. Furthermore,
      some ultrastructural improvement is observed in astroglial cells treated with
      almitrine suggesting some protecting role of Hsc70 on cell damage induced by
      hypoxia.

PMID- 7739754
TI  - Haloperidol reduces K(+)-evoked Ca(2+)-dependent D-[3H]aspartate release from rat
      hippocampal slices.
AB  - Rat hippocampal slices preloaded with D-[3H]aspartate, a non metabolizable
      analogue of L-glutamate, were superfused with artificial CSF. Depolarization was
      induced by 53.5 mM K+, in the presence of Ca2+ (1.3 mM) or Mg2+ (5 mM) to
      determine the Ca2+ dependent release. Haloperidol added in the superfusion medium
      at 100 microM reduced by about 60% the Ca2+ dependent release of D-[3H]aspartate.
      This drug at 20 microM or 100 microM inhibited the non-activated glutamate
      dehydrogenase (GDH) but had no effect on GDH activated by ADP (2 mM) or leucine
      (5 mM). In addition no effect was observed on phosphate activated glutaminase
      (PAG) in the presence either of 20 mM or 5 mM phosphate. These results indicate
      that the effect of haloperidol is exerted on presynaptic mechanisms regulating
      neurotransmitter release.

PMID- 7739755
TI  - Changes in brain energy metabolism, neurotransmitters, and choline during and
      after incomplete cerebral ischemia in spontaneously hypertensive rats.
AB  - In order to investigate changes in energy metabolism, neurotransmitters, and
      membrane disorder accompanying incomplete cerebral ischemia, a bilateral common
      carotid artery occlusion model of spontaneously hypertensive rats was utilized.
      We measured concentrations of ATP, phosphocreatine (PCr), lactate (Lac), glucose
      (Glu), acetylcholine (ACh), choline (Ch), and gamma-aminobutyric acid (GABA) in
      both the cerebral cortex and the subcortical regions after 1 h ischemia, 2 h
      ischemia, and 2 h reflow following 2 h ischemia, and then examined changes in
      concentrations of these substances during and after incomplete cerebral ischemia.
      Also, examined were interrelations of changes in these substance levels during
      ischemia. In the cerebral cortex, levels of ATP, PCr, Glu, and ACh decreased, and
      levels of Lac, Ch, and GABA increased during ischemia. After recirculation,
      levels of ATP, PCr, Ch, and GABA tended to return to the normal range. On the
      other hand, the Lac level remained in the ischemic range and the Glu level rose
      and greatly exceeded the normal range. With regard to ACh, most animals showed
      normal levels but some exceeded the normal range. Changes in the subcortical
      regions were qualitatively the same as those in the cerebral cortex during and
      after ischemia (except with Glu), but only smaller in degrees. Glu levels
      remained unchanged during ischemia. Correlation of the levels of these substances
      in the cerebral cortex was examined using normal and ischemic values. A high
      correlation was generally observed between ATP and other substance levels. The
      relations between ATP and either PCr or Glu levels were linear. The relation
      between ATP and ACh levels was logarithmic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7739756
TI  - Depletion of brain glutathione is accompanied by impaired mitochondrial function
      and decreased N-acetyl aspartate concentration.
AB  - The effect of depletion of reduced glutathione (GSH) on brain mitochondrial
      function and N-acetyl aspartate concentration has been investigated. Using pre
      weanling rats, GSH was depleted by L-buthionine sulfoximine administration for up
      to 10 days. In both whole brain homogenates and purified mitochondrial
      preparations complex IV (cytochrome c oxidase) activity was decreased, by up to
      27%, as a result of this treatment. In addition, after 10 days of GSH depletion,
      citrate synthase activity was significantly reduced, by 18%, in the purified
      mitochondrial preparations, but not in whole brain homogenates, suggesting
      increased leakiness of the mitochondrial membrane. The whole brain N-acetyl
      aspartate concentration was also significantly depleted at this time point, by
      11%. It is concluded that brain GSH is important for the maintenance of optimum
      mitochondrial function and that prolonged depletion leads also to loss of
      neuronal integrity. The relevance of these findings to Parkinson's disease and
      the inborn errors of glutathione metabolism are also discussed.

PMID- 7739757
TI  - Caffeine-induced locomotor activity: possible involvement of GABAergic
      dopaminergic-adenosinergic interaction.
AB  - Caffeine (10-40 mg/kg, p.o.) enhanced locomotor activity (LA). Administration of
      GABA antagonist, bicuculline (0.5-1.0 mg/kg, i.p.), potentiated this caffeine
      induced increase of LA, as well as LA of control rats. Treatment with the GABA
      agonist, muscimol (0.25-1 mg/kg, i.p.) or dopaminergic antagonist, haloperidol
      (0.25-1 mg/kg, i.p.) or muscarinic receptor blocker, atropine (3.75-5 mg/kg,
      i.p.), or inhibitor of acetylcholine esterase physostigmine (0.05-0.30 mg/kg,
      i.p.) or nicotine (0.5-1.5 mg/kg, i.p.) an nicotinic receptor agonist all
      decreased the LA of both caffeine-treated and control rats. Haloperidol-induced
      reduction in caffeine-induced increase in LA was found to be withdrawn with
      higher dose of caffeine. The dopamine agonist L-Dopa (75-150 mg/kg, p.o.) along
      with carbidopa (10 mg/kg, p.o.) increased the LA in control rats and potentiated
      the LA of caffeine treated rats. The haloperidol attenuated the bicuculline
      induced increase in LA and atropine or physostigmine attenuated the bicuculline
      or L-Dopa + carbidopa-induced increase in LA in both caffeine treated and control
      rats when those drugs were administered concomitantly with bicuculline or L
      Dopa+carbidopa. These results suggest that (a) the GABAergic system has direct
      role in the regulation of LA, and (b) caffeine potentiates LA by antagonism of
      the adenosine receptor and activation of the dopaminergic system which, in turn,
      reduces GABAergic activity through the reduction of cholinergic system.

PMID- 7739759
TI  - The effect of chronic chlorpromazine administration on monoamine levels in
      various regions of rat brain.
AB  - The neuroleptic drug, chlorpromazine (CPZ) has been shown to exert its
      antipsychotic effect by blocking post synaptic dopamine receptors. However, its
      effect on steady state levels of monoamines is still in discrepancy. In the
      present study, CPZ (4 mg/kg body weight) was administered intraperitoneally to
      adult Wistar rats chronically for 75 days and the levels of norepinephrine (NE),
      dopamine (DA) and 5-hydroxytryptamine (5-HT) were assayed in various brain
      regions by high performance liquid chromatography (HPLC). After the experimental
      period body and brain weights were not statistically different from controls. NE
      and 5-HT levels were increased only in hippocampus by 15% (p < 0.01) and 16% (p <
      0.01) respectively. DA levels were consistently increased in cortex by 39% (p <
      0.001), striatum-accumbens by 18% (p < 0.01), hippocampus by 27% (p < 0.01),
      hypothalamus by 34% (p < 0.001), cerebellum by 36% (p < 0.001) and brainstem by
      40% (p < 0.001) in CPZ treated rats compared to controls. The results suggest
      that chronic CPZ administration increases DA levels in almost all regions of
      brain and reflect the ability of CPZ to preferentially interfere with synaptic
      transmission mediated by DA in brain. It also suggests that this increase in DA
      might be responsible for certain side effects seen in patients after chronic CPZ
      treatment.

PMID- 7739758
TI  - Regulatory sites and effectors of D-[3H]aspartate release from rat cerebral
      cortex.
AB  - To study the effect of agents interfering with the biosynthesis and/or the K(+)
      evoked Ca(2+)-dependent release of neurotransmitter glutamate, rat cerebral
      slices were preincubated with Krebs-Ringer-HEPES-glucose-glutamine buffer (KRH
      buffer), loaded with D-[3H]aspartate and superfused with the preincubation medium
      in the presence or in the absence of Ca2+. The difference in radioactivity
      release divided by the basal release per min under the two conditions represented
      the K(+)-evoked Ca(2+)-dependent release. The agents used were: 1) Aminooxyacetic
      acid (AOAA), the inhibitor of transaminases, 2) Leucine (Leu), the inhibitor of
      phosphate activated glutaminase (PAG), 3) NH4+, the inhibitor of PAG, 4)
      Phenylsuccinic acid (Phs), the inhibitor of the mitochondrial ketodicarboxylate
      carrier, 5) ketone bodies, the inhibitors of glycolysis, 6) the absence of
      glutamine, the substrate of PAG. The results show that Leu, NH4+, Phs and the
      absence of Gln significantly increase the K(+)-evoked Ca(2+)-dependent release of
      radioactivity by 64%, 200%, 95% and 147% respectively, indicating that these
      agents are inhibitors of the K(+)-evoked Ca(2+)-dependent release of glutamate.
      Ketone bodies and AOAA had no effect. These results indicate that the major if
      not the exclusive biosynthetic pathway of neurotransmitter glutamate in rat
      cerebral cortex is through the PAG reaction and support a model for the pathway
      followed by neurotransmitter glutamate i.e. glutamate formed outside the inner
      mitochondrial membrane has to enter the mitochondrial matrix or is formed within
      it from where it can be extruded to supply the transmitter pool in exchange of
      GABA.

PMID- 7739760
TI  - The interaction of (1-4)-fragment of thymosin beta 4 with calmodulin-sensitive
      cAMP phosphodiesterase from hypothalamus.
AB  - Evidence was accumulated indicating that cyclic nucleotides are involved in
      regulation of growth, differentiation and function of lymphoid cells. It was
      previously shown that the N-fragment (1-4) of thymosin beta 4 (Ac-Ser-Asp-Lys-Pro
      OH) inhibits in vivo the entry of cell populations into S-phase. In the course of
      the study of the interrelationship between the immune and neuroendocrine systems
      we have found that the tetrapeptide caused incomplete competitive inhibition of
      hypothalamic calmodulin (CaM)-dependent phosphodiesterase (PDE) stimulated by
      CaM. In the presence of the peptide, the 20-fold increase of the constant for PDE
      activation by CaM was accompanied by an insignificant rise in the maximum rate of
      cAMP hydrolysis. The value of the inhibition constant (Ki) amounted to 600 nM. In
      the absence of CaM, the peptide at saturating concentrations reduced the basal
      activity of PDE nearly 2- to 3-fold. The effect of the peptide on PDE was
      noncompetitive with respect to cAMP. The results support our suggestion that the
      tetrapeptide realizes its effects in the immuno-neuroendocrine system by the
      mechanism of cyclic nucleotide metabolism.

PMID- 7739761
TI  - M3 muscarinic receptors on murine HSDM1C1 cells: further functional, regulatory,
      and receptor binding studies.
AB  - In the present studies, the pharmacology and regulation of the functional
      muscarinic receptors on HSDM1C1 cells were probed using phosphoinositide (PI)
      turnover assays. In addition, the receptor binding of the putative M3-selective
      radioligand, [3H]4-DAMP, to cell homogenates was characterized. Carbachol (EC50 =
      9 microM), (+)muscarine (EC50 = 4.5 microM) and cis-dioxolane (EC50 = 0.72
      microM) were full agonists which stimulated PI turnover by 13.3 +/- 1.0 fold
      above basal values. The potencies of numerous agonists in this assay system were
      relatively similar to their affinities in receptor binding assays. Exposure of
      HSDM1C1 cells to 10 nM-10 microM muscarine during the last 24h of [3H]myo
      inositol-labeling resulted in a concentration-dependent reduction in the cis
      dioxolane affinity and maximal PI response induced by subsequent treatment with
      cis-dioxolane. Pertussis toxin (5-2000 ng/ml) caused a partial reduction in the
      cis-dioxolane-induced PI turnover. Likewise, exposure of the HSDM1C1 cells to an
      active phorbol ester (TPA) resulted in a partial inhibition of the cis-dioxolane
      induced (100 microM) PI turnover. The half-maximal effect of TPA was produced at
      1.8 +/- 0.3 nM. [3H]4-DAMP binding to cell homogenates was of high affinity (Kd =
      0.19 +/- 0.04 nM) and moderate capacity (Bmax = 201 +/- 22 fmol/mg protein). The
      pharmacological specificity (4-DAMP > p-FHHSiD > dicyclomine > pirenzepine >
      methoctramine > AFDX-116 > gallamine) resembled that for [3H]NMS binding and
      correlated well with that observed for inhibition of PI turnover. These studies
      further support the identification of M3 receptors on HSDM1C1 cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7739762
TI  - A radiometric microassay for choline acetyltransferase. Some observations on the
      spinal cord of the chicken embryo.
AB  - This paper describes cation-exchange methods for separating acetyl[3H] coenzyme A
      from [acetyl-3H]choline. Blanks for the routine method were approximately 0.05%
      of the substrate radioactivity; product recoveries were approximately 97%. The
      cation-exchange method was more efficient than the standard methods using either
      anion-exchange chromatography or periodide precipitation. The cation-exchange
      method was also more specific than either of the other two standard methods for
      estimating choline acetyltransferase (ChAT) activity. ChAT activity was detected
      in the chicken lumbar spinal cord on embryonic day (E) 2 1/4 with the cation
      exchange method. This developmental stage is about 6 hours before the final
      mitosis of any neuroblast in the ventral horn. Total ChAT activity per lumbar
      spinal cord increased more than 10,000-fold between E 3 and E 18. Changes in ChAT
      activity in the lumbar spinal cord following limb-bud extirpation appeared to
      mirror (with a phase lag) the changes in the number of motoneurons in the lateral
      motor column.

PMID- 7739764
TI  - Regional alterations of thiamine phosphate esters and of thiamine diphosphate
      dependent enzymes in relation to function in experimental Wernicke's
      encephalopathy.
AB  - Thiamine phosphate esters (thiamine monophosphate-TMP; thiamine diphosphate-TDP
      and thiamine triphosphate-TTP) were measured as their thiochrome derivatives by
      High Performance Liquid Chromatography in the brains of pyrithiamine-treated rats
      at various stages during the development of thiamine deficiency encephalopathy.
      Severe encephalopathy was accompanied by significant reductions of all three
      thiamine phosphate esters in brain. Neurological symptoms of thiamine deficiency
      appeared when brain levels of TMP and TDP fell below 15% of normal values.
      Activities of the TDP-dependent enzyme alpha-ketoglutarate dehydrogenase were
      more severely reduced in thalamus compared to cerebral cortex, a less vulnerable
      brain structure. On the other hand, reductions of TTP, the non-cofactor form of
      thiamine, occurred to a greater extent in cerebral cortex than thalamus. Early
      reductions of TDP-dependent enzymes and the ensuing metabolic pertubations such
      as lactic acidosis impaired brain energy metabolism, and NMDA-receptor mediated
      excitotoxicity offer rational explanations for the selective vulnerability of
      brain structures such as thalamus to the deleterious effects of thiamine
      deficiency.

PMID- 7739763
TI  - Regional alterations of dopamine and its metabolites in rat brain following
      portacaval anastomosis.
AB  - Hyperammonemia and changes in brain monoamine metabolism have been proposed to
      contribute to the pathogenesis of the neuropsychiatric symptoms characteristic of
      human portal-systemic encephalopathy (PSE) resulting from chronic liver disease.
      Portacaval anastomosis (PCA) in the rat leads to sustained hyperammonemia and
      mild encephalopathy. In order to evaluate the role of dopamine (DA) metabolism in
      PSE, levels of DA and its metabolites were measured by HPLC with electrochemical
      detection in brain regions of rats with PCA at various stages of encephalopathy
      precipitated by ammonium acetate administration. Following ammonium acetate
      administration, rats with PCA rapidly develop severe neurological signs of
      encephalopathy progressing through loss of righting reflex to coma; sham-operated
      control animals administered ammonium acetate showed no such neurological
      deterioration. Concentrations of the DA metabolites DOPAC and HVA as well as [DA
      metabolites]/[DA] ratios, an indirect measure of DA turnover in brain, were
      increased in caudate-putamen, in cingulate and pyriform entorhinal cortices as
      well as in raphe nucleus and locus coeruleus. Increased DA metabolites, however,
      did not worsen at coma stages of PSE. Increased DA turnover thus appears to
      relate to early neuropsychiatric and extrapyramidal symptoms of PSE.

PMID- 7739765
TI  - Differences in effects of sultopride and sulpiride on dopamine turnover in rat
      brain.
AB  - Sultopride and sulpiride are both chemically similar benzamide derivatives and
      selective antagonists of dopamine D2 receptors. However, these drugs differ in
      clinical properties. We compared the effects of sultopride and sulpiride on
      dopamine turnover in rats following the administration of these drugs alone or in
      combination with apomorphine. The administration of sultopride or sulpiride
      markedly accelerated dopamine turnover in the rat brain. The increase in the
      level of dopamine metabolites in the striatum was more marked in the sultopride
      treated rats. Sulpiride affected the limbic dopamine receptors preferentially,
      whereas sultopride affected the striatal and the limbic dopamine receptors
      equally. A low dose of apomorphine induced a reduction in the concentration of
      dopamine metabolites in the striatum and the nucleus accumbens by approximately
      55%, but not in the medial prefrontal cortex. Sultopride was more effective in
      preventing an apomorphine-induced reduction in dopamine metabolite levels. These
      results from rat experiments would model the pharmacological differences observed
      between sultopride and sulpiride in clinical use.

PMID- 7739766
TI  - [Gene therapy for brain tumors: experimental treatment of malignant brain tumors
      using recombinant herpes simplex virus type 1 (series 7)].

PMID- 7739767
TI  - [Near-infrared spectroscopy].

PMID- 7739768
TI  - [Highlateral approach to the lesions around the upper cervical vertebrae and
      foramen magnum].
AB  - In the present paper, we describe the surgical techniques of high lateral
      cervical approach and its feasibility for the excision of tumors located in the
      ventral or lateral aspect of the upper cervical vertebrae and of the
      craniovertebral junction. The patient is positioned laterally on the operating
      table, but the operator's position and the skin incision are slightly altered
      depending on the location of the tumor. When the lesion is situated below C1, the
      ipsilateral shoulder is pulled down toward the back. The operator stands rostral
      to the head. The attachment of the sternocleidomastoid muscle to the mastoid is
      detached and reflected anteriorly through a retroauricular curved skin incision.
      The posterior cervical muscles such as the splenius capitis, longissimus capitis,
      semi-spinalis capitis are detached from the occipit and retracted posteriorly. At
      this point, the transverse process of C1 and the articular facet of the vertebrae
      of C2-C4 are identified by palpation. According to the tumor location, the
      muscles attached to the relevant transverse processes and facets are divided and
      reflected posteriorly. Through careful dissection, the cervical nerve roots and
      the vertebral artery are exposed. The root sleeves as well as thecal sac may be
      exposed by resecting the posterior two-thirds of the superior and inferior
      articular facets and the adjacent laminae of the vertebrae. In case the whole
      facet was removed, an iliac bone graft is placed between the remaining transverse
      processes and the laminae above and below for fixation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7739769
TI  - [Hemodynamics of the transverse sinus using cine angiography].
AB  - Numerous anatomical observations of the transverse sinus (TS) have been reported
      and features of this sinus, as assessed by cerebral angiography, are referred to
      in many monographs. However, there are no studies on the hemodynamics in the TS.
      We recently investigated the TS, using cerebral angiography with cinematographic
      films. The subjects were 35 patients who underwent angiography of 3 or 4 vessels
      at our institute, using Seldinger's method. The contrast material was infused
      manually. Cinematography permitted observation of the size of the bilateral TS
      and the direction of blood flow. Depending on the features of the bilateral TS,
      the patients could be divided into three groups. Type I (cases where the right TS
      was dominant) accounted for the highest percentage (54.3%, 19/35). In 11 of these
      19 cases, the left TS also showed antegrade blood flow. In 6 of the Type I group,
      the blood flow through the left TS was in two directions (towards the Torcular
      Herophili and towards the left sigmoid sinus). In the other two cases rated as
      Type I, the blood flow through the left TS was in the direction from the Torcular
      Herophili to the right TS. Fourteen cases (40.0%) were rated as Type II (in which
      both sinuses were similar in size). In 13 of these 14 cases, blood flow through
      the bilateral TS was almost symmetrical (Type II-A). In one of the 14 cases, the
      blood flow through the left TS was in two directions (towards the Torcular
      Herophili and towards the left sigmoid sinus).

PMID- 7739770
TI  - [Studies concerning the pathogenesis of trigeminal neuralgia caused by
      cerebellopontine angle tumors].
AB  - It has been well recognized that neurovascular compression can elicit trigeminal
      neuralgia (TN) and microvascular decompression surgery has become popular as a
      radical treatment of this clinical symptom. Cerebellopontine (C-P) angle tumors,
      however, as well known, can also cause TN. Four hundred fifty six patients with
      TN underwent posterior fossa exploration between 1984 and 1992 in our clinic, and
      among them, 45 (9.9%) patients harbored C-P angle tumors which were causative of
      TN. They included 22 epidermoids, 18 meningiomas and 5 neurinomas. The patient
      population consisted of 35 women and 10 men, ranging in age from 28 to 73 years,
      with a mean age of 51.7 years. The mean age of the patients of TN with tumors is
      considerably lower than that of neurovascular compression patients (61.0 years),
      particularly in cases of neurinomas (44.4 years) and epidermoids (48.0 years) (p
      < 0.01). Such difference in ages at the onset of symptom may be explained by the
      fact that the tumor growth in the C-P angle develops earlier than changes of the
      vasculature of the vertebrobasilar artery system by aging. Anatomical
      relationships between the 5th cranial nerve and offending arteries or tumors
      verified at surgery are as follows; Type A: The nerve is totally encased by the
      tumor. Type B: The axis of the nerve is distorted by the tumor. Type C: The nerve
      is shifted by the tumor and is compressed by the artery contralaterally. Type D:
      The nerve is compressed by the artery which was displaced by the tumor.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7739771
TI  - [A case report of dural sinus thrombosis: direct thrombolytic therapy using
      endovascular surgery].
AB  - Dural sinus thrombosis, a relatively rare disease, is difficult to diagnose
      because of variable symptomatic manifestations. We successfully treated a case of
      dural sinus thrombosis by direct thrombolysis using an endovascular technique in
      combination with postoperative anticoagulant therapy. The patient, a 19-year-old
      female, developed a headache affecting her whole head on December 13, 1993. She
      was admitted to our hospital the next day. Neurological examination upon
      admission revealed no neurological abnormalities, nor was there any abnormality
      in CT scan, either plain or enhanced, taken on the day of admission. The
      patient's consciousness deteriorated in the early morning of December 22. MRI and
      cerebral angiography revealed thrombi from the confluence of the sinuses to the
      right transverse and sigmoid sinus, with disturbed circulation through deep
      cerebral veins. Systemic thrombolytics, steroid and mannitol were started, but,
      on the next day, the third ventricle was compressed by bilateral swelling of the
      basal ganglia, with hydrocephalus. Since her consciousness deteriorated further
      despite ventricular drainage and barbiturate therapy, direct thrombolytic therapy
      was performed on December 25. A catheter was placed in the superior sagittal
      sinus, and 600,000 units of urokinase was locally injected, followed by
      postoperative anticoagulant therapy. The patient's condition improved rapidly. On
      CT scan, the bilateral swelling of the basal ganglia disappeared along with the
      hydrocephalus. At about 1 month after endovascular surgery, MRI and cerebral
      angiography revealed recanalization of the deep cerebral veins, straight sinus
      and confluence of sinuses with improved opacification of the left transverse
      sinus, although the right transverse sinus was found to be re-occluded.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7739772
TI  - [A case of spinal astrocytoma presenting spinal transverse sign due to
      hematomyelia].
AB  - An unusual case of cervical astrocytoma due to hematomyelia was reported. A 68
      year-old man was admitted to our institute because of sudden onset of paraplegia
      and urinary and bowel disturbance. CT and plain X ray on admission showed no
      abnormal findings, but emergency MRI revealed a high signal intensity area in Th
      8-9 level on T1 weighted image. Preoperative diagnosis was idiopathic
      hematomyelia and emergency laminectomy was performed. After the dural incision
      from Th 8-10, the intramedullary hematoma was totally removed, but at the
      cephalic portion within the hematoma cavity an abnormal tumorous tissue was
      detected. It was noticed with the bleeding sauce of hematomyelia, and it, too,
      was totally removed. The microscopic finding concerning the surgical specimen was
      fibrillary astrocytoma (grade 2), and its vascular component was relatively rich.

PMID- 7739773
TI  - [A long survival case of brain tumor considered as a metastatic tumor].
AB  - A case of long survival of brain tumor (well differentiated adenocarcinoma) was
      reported. A 55-year-old man was admitted in January, 1986, because of a one month
      history of progressive headache, dizziness and gait disturbance. CT scans
      revealed an enhancing tumor in contact with the falx in the right frontal lobe.
      The tumor was totally removed. The histopathological diagnosis was that of a well
      differentiated adenocarcinoma. The primary site of the adenocarcinoma was not
      detected. No chemotherapy or radiation therapy was given. Four years and 7 months
      after surgery CT scans demonstrated a recurrent tumor as a bilaterally expanding
      falx meningioma. Nearly total removal of the tumor was again performed and
      diagnosed as adenocarcinoma. Examinations to detect the primary site and other
      metastatic lesions were negative again. On May 1993, the patient died because of
      the intracranial dissemination of tumor without extracranial lesions. The period
      from the first operation to his death was 7 years and 5 months. This is a case of
      long survival of intracranial cancer, which was considered as a metastatic tumor,
      though the primary site and other metastatic lesions were not detected. The tumor
      in this case showed the atypical features of a metastatic adenocarcinoma. For
      example, the primary and recurrent tumors resembled a parasagital or falx
      meningioma in shape and they grew slowly. Therefore, there is a possibility that
      the tumor was actually a primary adenocarcinoma, which might have arisen from the
      embryologically migrated cells of the mucous membrane or from ectopic epithelial
      cells.

PMID- 7739774
TI  - [Posterolateral extradural approach for total excision of spinal meningeal cyst
      (type Ia): case report].
AB  - Lateral thoracic meningocele is an uncommon disorder known to occur with high
      frequency in patients with neurofibromatosis. We report a case not accompanied by
      neurofibromatosis and describe the operative technique utilizing a posterolateral
      extradural approach. A 41-year-old man was referred to our cardiologic clinic for
      severe anterior chest pain. Plain chest X-ray demonstrated an oval mass lesion in
      the right 9th to 10th thoracic paravertebral region. Magnetic resonance imaging
      revealed a cystic mass at the 10th thoracic intervetebral foramen without
      distortion of the spinal cord. Signal intensity of the cystic mass was the same
      as the cerebrospinal fluid around the spinal cord. In the prone position,
      laminotomy of the 10th vertebral only was carried out. A pulsatile round mass in
      continuity with the dura mater was exposed. The wall of the sac, which was
      thickened with CSF, was identified. The neck of the menigocele was ligated with
      the help of an aneurysm needle. The patient's severe chest pain disappeared
      postoperatively.

PMID- 7739775
TI  - [Ventilatory insufficiency due to upper cervical injury treated by diaphragm
      pacing: a case report].
AB  - A 33-year-old man suffered chronic ventilatory insufficiency with tetraplegia
      after an operation for atlantoaxial dislocation. He was alert and his tetraplegia
      gradually improved. However, continuous mechanical ventilation was necessary for
      him. Thirteen months after the operation, a diaphragm pacer (Avery Laboratory
      Inc.) was implanted on the right phrenic nerve in the cervical region. Nineteen
      days after the implantation of the right side pacer, a left side diaphragm pacer
      was also implanted. Diaphragm pacing was started two weeks after the second
      implantation. The pacing period was gradually prolonged and continuous pacing for
      9 hours by the right side pacer and three hours by the left side pacer was able
      to be obtained. One year after implantation, twelve continuous hours of diaphragm
      pacing became possible. During diaphragm pacing, blood gas analysis was
      satisfactory and the patient could move sitting on a wheel chair, watch
      television and write letters using a word processor. We were unable to achieve
      total ventilatory support for him using these diaphragm pacers. We thought that
      the main cause of our partial failure originated from the procedure used in
      implanting the electrode onto the phrenic nerve. Left side pacing needs higher
      amplitude than that used on the right side to obtain sufficient tidal volume. The
      patient refused our continuing the left side pacing because of pain around the
      anterior chest and shoulder. Another problem to be watched is diaphragm fatigue.
      However, diaphragm pacing has been continued for six years and it has been useful
      in improving his quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7739776
TI  - [Medulla oblongata compression by tortuous vertebral artery: case report].
AB  - We reported a case of a 58-year-old woman who suffered from progressive
      tetraparesis and sensory disturbance caused by compression of the medulla
      oblongata brought about by bilateral tortuous vertebral arteries. The
      neurological examination on admission revealed tetraparesis, sensory disturbance
      in all modalities below the level of C2, onion-skin pattern sensory disturbance
      of the face, and motor weakness of the sternocleidomastoid muscles. X-ray films
      of the cervical spine showed OPLL at the level of C2.3, but on MRI the dural
      theca was not seen to be compressed at that level. MRI and vertebral angiography
      demonstrated ventrolateral compression of the medulla oblongata by bilateral
      tortuous vertebral arteries. After suboccipital craniectomy and C1.4 laminectomy,
      decompression of the medulla oblongata was performed. Both vertebral arteries
      were compressing the medulla oblongata at the ventrolateral side. Transposition
      of the vertebral arteries seemed impossible due to perforating branches to the
      medulla. After section of the dentate ligaments at C1 level, the medulla
      oblongata was decompressed and moved backward. Some small pieces of Dacron were
      inserted between the arteries and the medulla, in order to decrease the pulsatile
      effect of the vertebral arteries. Postoperatively, the patient's tetraparesis and
      sensory disturbance gradually improved. There are 6 reported cases concerning
      compression of the medulla oblongata by the vertebral artery. As MRI becomes more
      frequently used in neurological situations, it is important to keep the presence
      of such an entity in mind.

PMID- 7739777
TI  - [Ruptured distal anterior cerebral artery aneurysm and diagnostic dyspraxia: a
      case report].
AB  - A case of ruptured distal anterior cerebral artery aneurysm presenting with
      diagnostic dyspraxia is presented. A 54-year-old female was referred to our
      hospital with the complaint of sudden onset of headache followed by disturbance
      of consciousness. CT and MRI revealed subarachnoid hemorrhage with hematomas in
      the interhemispheric fissure and the supracallosal area, and CAG revealed a left
      sided callosomarginal artery aneurysm. During and after hospitalization, she
      showed diagnostic dyspraxia characterized by behavior of both her hands opposite
      to what might be expected e.g. when she tried to pick up a bowl, both her hands
      moved forward and held it at once; she wiped her head and face with toilet paper
      after urination. At times her hands behaved in opposite ways. For example, while
      folding cloths, her right hand tended to fold them while the left hand tended to
      unfold them; when she put on a sweater, as the right hand put it on, the left
      hand took it off; when she put her shirt into her trousers, one hand pushed it in
      while the other hand pulled it out. This unusual behavior was considered to be
      caused by the impairment of the corpus callosum due to compression by the
      hematoma. It disappeared gradually over a period of one year. Involuntary motor
      behavior of the left hand while the right hand is in voluntary action is known as
      diagnostic dyspraxia. Although this symptom has rarely been reported so far in
      cases of ruptured distal anterior cerebral artery, it may become noticed more
      frequently through careful observation.

PMID- 7739779
TI  - [Marked dilatation of the bilateral common carotid artery: a case report].
AB  - We reported a rare case of marked dilatation of the bilateral common carotid
      artery (CCA) associated with stenosis of the left middle cerebral artery (MCA). A
      64-year-old female was admitted with right hemiparesis and dysarthria. She was
      hospitalized 2 years ago for cholecystitis. For 5 years, she has been under
      medical treatment for hypertension, diabetes mellitus, hyperlipidemia, cardiac
      failure associated with hypertrophic cardiomyopathy, and atrial fibrillation.
      Brain CT scan showed infarction of the left corona radiata. Angiography revealed
      marked dilatation of the bilateral CCA and the internal carotid artery (ICA),
      moderate dilatation of the innominate artery and the right subclavian artery,
      kinking of the right CCA, diverticular outpouching of the left ICA, and stenosis
      of the right external carotid artery and the left MCA. Breast CT scan revealed
      moderate dilatation and marked calcification of the ascending aorta and the
      aortic arch. Laboratory examination did not show any sign of inflammation,
      rheumatoid factor (RA), antistreptolysis-O (ASLO) and antinucleotic antibody.
      Based on the clinical course, radiological findings and laboratory data, possible
      diagnosis of the dilatation of the bilateral CCA was discussed with particular
      emphasis on arteriosclerotic aneurysm and aortitis syndrome.

PMID- 7739778
TI  - [A case of ruptured true posterior communicating artery aneurysm thirteen years
      after surgical occlusion of the ipsilateral cervical internal carotid artery].
AB  - A case is presented of ruptured "true" posterior communicating artery aneurysm
      thirteen years after surgical occlusion of the ipsilateral cervical internal
      carotid artery. A 58-year-old female developed the sudden onset of blepharoptosis
      on the right side. She had had a right superficial temporal artery-middle
      cerebral artery anastomosis and a surgical occlusion of the right cervical
      internal carotid artery 13 years earlier for a subarachnoid hemorrhage that
      occurred as the result of a ruptured aneurysm of the right internal carotid
      artery. Neurological examination on admission revealed an occulomotor palsy on
      the right. Cerebral angiograms demonstrated an aneurysm arising from the right
      posterior communicating artery itself near the right posterior cerebral artery.
      Also, the right intracranial internal carotid artery was supplied through the
      right posterior communicating artery. Five days later she experienced the sudden
      onset of severe headache. CT scan showed subarachnoid hemorrhage in the ambient
      cistern. Neck clipping of the aneurysm was successfully performed by the
      contralateral zygomatic approach. The postoperative course was uneventful. It has
      been well known that internal carotid artery occlusion may be associated with
      cerebral aneurysm in some cases. However, it seems to be very rare that a "true"
      posterior communicating artery aneurysm should occur following the ipsilateral
      carotid artery occlusion. Hemodynamic factors were strongly suggested as the
      reason for aneurysmal formation in this case.

PMID- 7739780
TI  - [Spontaneous regression of cerebral arterio-venous malformation following major
      artery thrombosis proximal to dominant feeders: a case report].
AB  - A rare case of spontaneous regression of cerebral arterio-venous malformation
      (AVM) is reported. A 76-year-old male was admitted to Juzen General Hospital due
      to generalized convulsion on August 24, 1987. On admission, results of physical
      and neurological examinations were normal. Plain CT scans showed an iso-density
      lesion with a slightly high density spot in the left frontal lobe, and enhanced
      CT scans showed multiple, irregularly tubular enhancements in the lesion. Left
      carotid angiogram (CAG) demonstrated an arteriovenous malformation (AVM) in the
      left frontal lobe, which was fed by the left ACA and MCA and drained by the
      ascending cerebral vein and superficial Sylvian vein. There was also an anterior
      communicating artery aneurysm. At the patient's request, he was treated
      conservatively and was discharged without neurological deficit. Though he
      continued to take anticonvulsants thereafter, he felt weakness or numbness of the
      right extremities once a year. Five years after the first admission, he developed
      sudden onset of right hemiparesis, aphasia and consciousness disturbance. On
      admission, his platelet aggregation function was elevated. At this time, enhanced
      CT scans did not show any enhanced area in the left frontal lobe where AVM had
      been found previously. T2-weighted magnetic resonance image showed a mixed
      intensity area without any flow void phenomenon suggesting thrombosis of the
      nidus. Left CAG demonstrated occlusion of the A1-A2 junction of the anterior
      cerebral artery and disappearance of the AVM. He was treated conservatively
      again, and was discharged without neurological deficit.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7739781
TI  - ATP stimulated catecholamine secretion: response in perfused adrenal glands and a
      subpopulation of cultured chromaffin cells.
AB  - Extracellular ATP is shown to induce catecholamine secretion in bovine chromaffin
      cells. Our data indicate that cells in culture gradually increase their response
      to ATP, and we have separated freshly isolated cells on a density gradient and
      found that the lighter cells develop a much stronger response to ATP than do the
      heavier cells. To see if the ATP sensitivity is physiological, we have perfused
      intact adrenal glands. ATP induces a greater secretory response from glands than
      does acetylcholine without causing preferential secretion of norepinephrine or
      epinephrine. These data show that the response to ATP found in cultured cells is
      not an artifact of cell culture, and that ATP co-released with catecholamines
      from the storage vesicles may have a significant physiological role.

PMID- 7739782
TI  - Participation of peroxynitrite in acetylcholine release induced by nitric oxide
      generators.
AB  - Peroxynitrite is a product produced by spontaneous reaction of nitric oxide (NO)
      with superoxide. Functional roles of peroxynitrite in the release of endogenous
      acetylcholine evoked by NO generators has been examined using primary-cultured
      cerebral cortical neurons. NO generators, such as sodium nitroprusside and S
      nitroso-N-acetylpenicillamine, dose-dependently increased the release of
      acetylcholine (ACh); such increase of the release was significantly suppressed by
      hemoglobin which has the capacity to abolish biological effects of NO. Two types
      of superoxide scavengers, Cu2+, Zn2+ superoxide dismutase and ceruloplasmin,
      significantly reduced the NO-evoked ACh release. These results indicate that NO
      requires superoxide to evoke the release of ACh. Synthesized peroxynitrite evoked
      the release of ACh from cerebral cortical neurons in a dose-dependent manner.
      Thus, it is indicated that the NO-evoked ACh release is mediated, at least in
      part, by peroxynitrite produced by the reaction of NO with superoxide.

PMID- 7739783
TI  - Effects of allopurinol on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      induced neurochemical changes in the striatum and in the brainstem of the rat.
AB  - Levels of uric acid, xanthine, hypoxanthine, ascorbic acid (AA), dehydroascorbic
      acid (DHAA), glutathione (GSH), noradrenaline (NA), dopamine (DA),
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) were
      determined in the striatum and/or in the brainstem of 3-month-old male Wistar
      rats, given allopurinol (500 mg/kg day by gavage) for 3 days before a single MPTP
      52 mg/kg dose i.p. Allopurinol alone decreased uric acid and hypoxanthine levels
      in the striatum and in the brainstem; moreover, allopurinol increased AA
      oxidation and decreased striatal DA metabolites. Allopurinol affected neither
      regional MPTP and MPP+ levels nor the MPTP-induced inhibition of striatal DA
      oxidative metabolism. On the contrary, the MPTP-induced increase in uric acid
      levels and decrease in xanthine, hypoxanthine and NA levels were fully
      antagonised. Such findings demonstrate that the claimed MPP(+)-induced oxidative
      stress mediated by xanthine oxidase may be involved at least in the NA depletion;
      moreover, uric acid may have a physiological role as an active component of the
      neuronal antioxidant pool.

PMID- 7739784
TI  - [Ca2+] modulates the ratio between cycloxygenase and lipoxygenase metabolism of
      arachidonic acid in homogenates of hippocampal astroglial cultures.
AB  - While studying the enzymatic processing of arachidonic acid (AA) to eicosanoids
      in homogenates of hippocampal astrocytes, we observed that all the HPLC peaks
      corresponding to AA metabolites displayed significantly different levels
      depending on the presence or not of free Ca2+ in the incubation medium. A
      specific pattern was noticed, i.e. lipoxygenase (LOX) derivatives, in particular
      12-hydroxyeicosatetraenoic acid (12-HETE), showed higher levels in medium
      containing 1 mM Ca2+, while cycloxygenase (COX) products including prostaglandins
      (PG) F2 alpha, E2 and D2 and 12-hydroxyhepatadecatrienoic acid (12-HHT), were
      higher in Ca(2+)-free medium. COX metabolism exceeded LOX metabolism by threefold
      in Ca(2+)-free medium, while it was only 60% of it in 1 mM Ca2+. The total amount
      of AA processed under the two conditions was identical. These data suggest that
      free [Ca2+] influences the pattern of AA metabolites formed in hippocampal
      astrocytes, with possible important implications in view of the distinct roles
      played by COX and LOX eicosanoids in synaptic transmission and neurotoxicity in
      this area.

PMID- 7739785
TI  - Glial fibrillary acidic protein mRNA increases at proestrus in the arcuate
      nucleus of mice.
AB  - Glial fibrillary acidic protein (GFAP) increases during proestrus in astrocytes
      of the hypothalamic arcuate nucleus (ARC). These changes are associated with
      altered astrocyte-neuron contacts and synaptic remodelling, during preparation
      for the preovulatory gonadotrophin surge. This study of young C57BL/6J mice
      showed transient elevations of GFAP mRNA on proestrus in the ARC by in situ
      hybridization. Basal GFAP mRNA was regained within 18 h. We hypothesize that
      changes in astrocytic GFAP on proestrus result from elevations of GFAP mRNA that
      are, in turn, driven by ovarian secretions of estradiol.

PMID- 7739786
TI  - Phenotypic changes induced by replating of early post-natal rat chromaffin cells.
AB  - Postnatal chromaffin cells from rat adrenal medulla in culture respond to NGF by
      expressing neuronal traits. The replating of chromaffin cells after
      trypsinization produced neurite growth in a manner similar to that of NGF. The
      combination of replating and NGF exposure did not induce phenotypic changes over
      and above those observed by NGF alone. The morphological changes are independent
      of the preliminary culture conditions. The results of this study demonstrate for
      the first time that simple replating of young chromaffin cells can induce
      neuronal traits indistinguishable from those observed with NGF.

PMID- 7739788
TI  - Astrocytosis in wobbler mouse spinal cord involves a population of astrocytes
      which is glutamine synthetase-negative.
AB  - Mice affected by the wobbler mutation are characterized by a muscular atrophy
      associated with motoneuron degeneration. As soon as the first clinical signs of
      the disease appear, reactive astrocytes, strongly glial fibrillary acidic protein
      (GFAP)-positive, are observed in the spinal cord grey matter. They become
      prevalent at all levels with disease progression. Immunostaining of glutamine
      synthetase (GS) shows that these reactive astrocytes are never GS-positive. The
      activity and protein amounts of GS remain normal in wobbler spinal cord although
      astrocytosis develops. Thus, gliosis in the wobbler mouse seems to involve a
      subpopulation of astrocytes, which is strongly GFAP-positive but GS-negative.

PMID- 7739787
TI  - Immunohistochemical localization of glutathione S-transferase pi in rainbow trout
      olfactory receptor neurons.
AB  - In the fish olfactory system, glutathione S-transferases (GST) which detoxify
      electrophilic substances and participate in reactions of lipophilic compounds,
      may be active in the biotransformation of odorants and xenobiotics. In this study
      GST activity in the rainbow trout olfactory mucosa was high (477.6 +/- 218
      nmol/min per mg protein). The GST pi class was demonstrated by Western immunoblot
      analysis and localized by immunofluorescence to the dendritic and perinuclear
      regions of olfactory receptor neurons; areas previously shown to contain elevated
      glutathione. The presence of GST and glutathione in fish olfactory receptor
      neurons suggests that these cells utilize the glutathione pathway.

PMID- 7739789
TI  - Interaction of fluorescein derivatives with glibenclamide binding sites in rat
      brain.
AB  - In rat brain, [3H]glibenclamide binds with high affinity to sulfonylurea
      receptors associated with ATP-sensitive potassium (KATP) channels. KATP channels
      may play a modulatory role in neurotransmitter release and are involved in acute
      pathological events occurring in the brain. Fluorescein derivatives, which are
      suitable tools for the labelling of nucleotide binding sites, influence KATP
      channels and sulfonylurea receptors properties in insulinoma and cardiac cells.
      In this study, a negative allosteric action of fluorescein derivatives on
      glibenclamide binding sites has been shown in rat cortical neurons. This supports
      the hypothesis of interactions between nucleotide- and sulfonylurea-binding sites
      within the sulfonylurea receptor.

PMID- 7739790
TI  - Internal representation of gaze direction with and without retinal inputs in man.
AB  - The contribution of retinal and extraretinal signals to the coding of eye
      position in the head was studied in human subjects (Ss). Horizontal saccades were
      produced in darkness. For some trials, before returning gaze direction to the
      starting position, a visual signal briefly stimulated the foveal retina. Results
      showed that this retinal input helped Ss to perceive gaze orientation more
      accurately after the saccade suggesting that the internal representation of eye
      position was improved when both extraretinal and retinal signals were available.

PMID- 7739791
TI  - Linkage between brain serotonin concentration and the sex-specific part of the Y
      chromosome in mice.
AB  - The implication of the sex-specific part of the Y-chromosome (YS-SP) on brain
      serotonin (5-HT) level was investigated using congenic strains for this
      chromosomal region. The 5-HT level, which was higher in the NZB than in the CBA/H
      strain of mice, was depleted by the transfer of the YS-SP from NZB on CBA/H
      whereas the transfer of the YS-SP from CBA/H on NZB had no effect. The variations
      of 5-HT levels were not correlated with plasma testosterone concentration which
      is also dependent of the YS-SP.

PMID- 7739792
TI  - Effects of baclofen on medial vestibular nucleus neurones in guinea-pig brainstem
      slices.
AB  - Using intracellular recordings of medial vestibular nucleus neurones (MVNn) in
      guinea-pig brainstem slices, the effects of baclofen, a specific agonist of the
      metabotropic GABAB receptors, were tested on the three main types of MVNn (A, B
      and B + LTS MVNn) that were previously identified in this nucleus. Regardless of
      their type, almost all MVNn were hyperpolarized and inhibited by baclofen. These
      hyperpolarizing effects persisted following either the addition of tetrodotoxin
      (TTX) in the perfusion medium, or in the presence of a high Mg2+/low Ca2+
      solution known to block synaptic transmission. These results demonstrate that all
      types of MVNn are endowed with postsynaptic GABAB receptors.

PMID- 7739794
TI  - Two types of mitochondria are evidenced by protein kinase C immunoreactivity in
      the Muller cells of the carp retina.
AB  - The localization of protein kinase C (PKC) was studied immunocytochemically in
      the Muller cells of the carp retina. Electron microscope immunocytochemistry
      (using a monoclonal antibody to the alpha and beta isoenzymes of PKC) showed PKC
      immunoreactivity mainly inside some mitochondria, especially along the
      mitochondrial cristae whereas other mitochondria in the same Muller cells showed
      no staining. Despite a detailed analysis we did not find any significant
      morphological difference between labeled and unlabeled mitochondria. These
      results demonstrate, for the first time, the presence of PKC immunoreactivity
      inside mitochondria and suggest that individual mitochondria may differ in signal
      transduction pathway.

PMID- 7739793
TI  - Calyculin-A-induced fast neurite retraction in nerve growth factor-differentiated
      rat pheochromocytoma (PC12) cells.
AB  - Rat pheochromocytoma (PC12) cells were treated with nerve growth factor (NGF) for
      3-4 days. They formed growth cones and extended neurites. Addition of the
      phosphatase inhibitor calyculin A (CL-A) caused a concentration-dependent
      complete retraction of neurites within 15 min. Retraction of growth cones started
      with the filopodia still present. The cell bodies acquired a grape-like shape
      opposite to the cell nucleus. These morphological changes were reversible. After
      washout of the inhibitor, the cell bodies recovered to normal shape within about
      30-60 min while neurites started to grow again within 1 day. Okadaic acid (OA)
      which, compared to CL-A, is less potent as a PP-1 and equally potent as a PP-2A
      class inhibitor, caused neurite retraction only when added at more than a
      thousand-fold higher concentration than CL-A. Ca2+ levels within neurites and
      cell bodies remained stable and low during neurite retraction as measured with
      fura-2. However, cells treated with CL-A showed reduced activity of voltage-gated
      Ca2+ channels. The results suggest that the observed reversible changes in cell
      morphology occur at a constant low Ca2+ level and are most likely due to the
      inhibition of PP-1 class phosphatases.

PMID- 7739795
TI  - An L-cysteine sulfinic acid-sensitive metabotropic receptor mediates increased
      cAMP accumulation in hippocampal slices.
AB  - The excitatory amino acid (EAA), L-cysteine sulfinic acid (L-CSA), elicited a
      dose-dependent increase in cAMP accumulation in adult rat hippocampus that was
      not blocked by ionotropic glutamate receptor antagonists. Therefore, the
      possibility was examined that L-CSA activates the (1S,3R)-amino-1,3
      cyclopentanedicarboxylic acid (1S,3R-ACPD)-sensitive metabotropic glutamate
      receptor (mGluR) that increases cAMP by potentiating responses elicited by
      adenosine or other agonists of receptors coupled to adenylate cyclase via Gs.
      Like 1S,3R-ACPD, L-CSA induced a cAMP response that was inhibited by the
      adenosine receptor antagonist, 8-para-sulfyltheophylline, and by adenosine
      deaminase. In contrast to the 1S,3R-ACPD-induced cAMP response, the L-CSA-induced
      response was not potentiated by the adenosine uptake inhibitor, dipyridamole.
      Taken together with the previous finding that L-CSA does not potentiate cAMP
      responses elicited by agonists of receptors that activate Gs, these data suggest
      that L-CSA increases cAMP accumulation by activating a metabotropic EAA receptor
      that is different from the 1S,3R-ACPD-sensitive mGluR associated with
      potentiation of cAMP responses.

PMID- 7739796
TI  - Appearance of deteriorated neurons on regionally different time tables in rat
      brain thin slices maintained in physiological condition.
AB  - Brain slices are widely used for electrophysiological experiments. However, the
      time table of the chronological cell deterioration and its regional difference in
      slices are unknown. The argyrophil III staining method can demonstrate
      deteriorated ('collapsed') neurons specifically. Therefore we studied the
      appearance of the 'collapsed' neurons with time in coronal brain 'thin' slices
      maintained in vitro to evaluate possible regional differences in vulnerability.
      In the hippocampus, CA1 pyramidal, dentate gyrus granule, and non-pyramidal cells
      in any subfield became argyrophilic most easily, as did layer V-VI pyramidal
      neurons in the neocortex. These results suggest that some subclasses of neurons
      in brain slices degrade earlier than others even when maintained in physiological
      condition.

PMID- 7739797
TI  - Reciprocal IL-1 beta gene expression in medial and lateral hypothalamic areas in
      SART-stressed mice.
AB  - Specific alteration of rhythm of temperature (SART) stress has been found to
      induce thymic atrophy via activation of the hypothalamus-pituitary-adrenal (HPA)
      axis. We demonstrate here that SART stress induces increment of IL-1 beta mRNA
      levels in the medial hypothalamic area (MHA) and decrement of IL-1 beta mRNA
      levels in the lateral hypothalamic area (LHA). The altered levels of IL-1 beta
      expression in these loci return to those of non-stressed mice upon cessation of
      the stress. These data imply that the reciprocal wave of SART stress-induced IL-1
      beta gene expression in MHA and LHA may contribute to activation of the HPA axis
      and the resulting immunological dysfunction.

PMID- 7739798
TI  - Reduced and oxidized forms of glutathione and alpha-tocopherol in the
      cerebrospinal fluid of parkinsonian patients: comparison between before and after
      L-dopa treatment.
AB  - In the cerebrospinal fluid of untreated patients with Parkinson's disease (PD)
      the concentrations of reduced glutathione (GSH) and alpha-tocopherol (alpha-TOH)
      were unaltered but the concentration of oxidized glutathione (glutathione
      disulfide, GSSG) (P < 0.001), the GSSG/GSH ratio (P < 0.06), alpha-tocopherol
      quinone (alpha-TQ) (P < 0.001), and the alpha-TQ/alpha-TOH ratio (P < 0.01) were
      reduced significantly. In L-dopa-treated patients, the concentrations of GSH,
      GSSG, and the alpha-TQ concentration and the alpha-TQ/alpha-TOH ratio (P < 0.05)
      increased compared with untreated PD patients. These results suggest that
      oxidation of GSH and alpha-TOH is decreased in untreated PD patients, but is
      activated to a control level or more after L-dopa treatment.

PMID- 7739799
TI  - Interaction of beta-amyloid peptides with integrins in a human nerve cell line.
AB  - beta-Amyloid accumulates as extracellular aggregates in Alzheimer's-afflicted
      brain tissue, but it also is secreted by healthy tissue, for reasons not yet
      established. One possibility is that beta-amyloid, which contains a sequence
      (RHDS) homologous to the cell-binding domain of fibronectin, may modulate
      integrin function, a possibility supported by previous data from non-neuronal
      cells (Ghiso et al., Biochem. J., 288 (1992) 1053-1059). The current work shows
      that functional interaction with beta-amyloid peptides is also supported by
      integrins in neuronal cells. Experiments used the SH-SY5Y human neuroblastoma
      cell line, which was shown to contain integrins that mediated cell adhesion to
      substratum-bound fibronectin. Adhesion to fibronectin was partially blocked by
      synthetic beta-amyloid peptides containing the RHDS sequence. beta-Amyloid
      sequences adsorbed to substratum themselves were found to mediate cell adhesion,
      although less effectively than fibronectin. Anti-integrin blocked the peptide
      mediated adhesion, at doses commensurate with those blocking fibronectin-mediated
      adhesion. The data support the hypothesis that beta-amyloid peptides could
      physiologically, and perhaps pathogenically, modulate the activity of neuronal
      integrins, important cell surface receptors known to control protein kinase
      activities, Ca2+ levels, gene expression and organization of the cytoskeleton.

PMID- 7739800
TI  - Topographic distributions of monoamine oxidase-B-containing neurons in the mouse
      striatum.
AB  - We have recently documented the presence of cholinergic neurons containing
      monoamine oxidase (MAO)-B activity in the striatum of C57BL/6 mouse. In the
      present study, we have mapped the topographical distributions of MAO-containing
      neurons in the mouse striatum. Positive neurons were located in the striatum of
      the entire rostralcaudal extent. However, the distribution of MAO-containing
      neurons was not uniform in the striatum. The larger number of positive neurons
      were located in the dorsal region of the C57BL/6 mouse striatum, in contrast to
      the uniform distributions of choline acetyltransferase-immunoreactive neurons in
      the mouse striatum. The present results suggest that cholinergic neurons are
      functionally heterogenous in the mouse striatum.

PMID- 7739801
TI  - Antinociceptive effect of intrathecally administered pituitary adenylate cyclase
      activating polypeptide (PACAP) on the rat formalin test.
AB  - It has been reported that pituitary adenylate cyclase activating polypeptide
      (PACAP) is a sensory neuropeptide and that it is contained in capsaicin sensitive
      fibers. PACAP occurs as two variants, PACAP27 and the C-terminally extended
      PACAP38. We examined the effect of intrathecally administered PACAP27 and PACAP38
      on the rat formalin test which is considered to be a model of animal pain induced
      by inflammation. Fifty microliters of 5% formalin was injected subcutaneously in
      the plantar surface of the right hind paw. To analyze the effect of PACAP27 and
      PACAP38, the instances of spontaneous flinching were counted. Administration of
      either PACAP27 or PACAP38 resulted in a monotonically dose-dependent reduction in
      the instances of flinching behavior. These results suggested that PACAP may play
      an important role in inhibiting the transmission of the nociceptive information
      evoked by inflammation.

PMID- 7739802
TI  - Transfecting neurons and glia in the rat using pH-sensitive immunoliposomes.
AB  - Immunoliposomes were constructed using antibody 5-113 (directed to an antigen on
      the external surface rat glial cells), the antibody Thy 1.1, and a non-immune
      antibody. The antibodies were conjugated to N-gluytaryl-phosphatidylethanolamine.
      Liposomes were constructed with these conjugated antibodies, other lipids and a
      beta-galactosidase plasmid under the control of the cytomegalovirus promoter.
      When immunoliposomes decorated with one of three different antibodies were
      injected into the brain or spinal cord of adult rats, the X-gal reaction product
      was observed in neurons, astrocytes and vascular elements. There was an increase
      in neuronal labeling when animals were injected with Thy 1.1 conjugated liposomes
      and there was an increase in glial labeling in animals injected with 5-113
      liposomes. In spinal cords, the immunoliposomes appear to penetrate a substantial
      distance, transfecting neurons several centimeters from the site of delivery.
      These data suggest that immunoliposomes may provide an effective transfection
      system for gene delivery in the CNS.

PMID- 7739803
TI  - Ultrastructure of eosinophilic inclusion bodies in the amygdala-parahippocampal
      region of aged squirrel monkeys treated with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine, a dopaminergic neurotoxin.
AB  - Eosinophilic neuronal inclusions resembling cortical Lewy bodies have been
      observed in the amygdala-parahippocampal region of aged 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-treated squirrel monkeys. Electron microscopy in six monkeys
      revealed a composition of curving bundles of 16-17 nm filaments, arranged in a
      ball shape or as a cap adjacent to the nerve cell nucleus. The main difference
      between the monkey inclusions and human cortical Lewy bodies was the random
      orientation of the filaments in the human inclusion bodies.

PMID- 7739804
TI  - Leukemia inhibitory factor mRNA is expressed in cortical astrocyte cultures but
      not in an immortalized microglial cell line.
AB  - Leukemia inhibitory factor (LIF) is a multifunctional cytokine synthesized by a
      variety of cell types. In the nervous system LIF affects neuronal
      differentiation, and may be important during cerebral infection and inflammation.
      To clarify the cellular source of LIF in the brain, we examined the expression of
      LIF mRNA by primary cortical astrocyte cultures and an immortalized microglial
      cell line. The microglial cell line did not express LIF mRNA in response to pro
      inflammatory agents such as lipopolysaccharide (LPS) that induced expression of
      other cytokine mRNAs. In contrast, primary astrocyte cultures grown in serum
      containing medium expressed LIF mRNA constitutively, and this expression was
      regulated by pro-inflammatory and anti-inflammatory stimuli. Agents which
      activate the cAMP and protein kinase C second messenger systems also increased
      LIF mRNA in astrocyte cultures. These results suggest that astrocytes, but not
      microglia, may be an important source of LIF during cerebral inflammation and
      infection.

PMID- 7739805
TI  - Role of peri-axonal inflammation in the development of thermal hyperalgesia and
      guarding behavior in a rat model of neuropathic pain.
AB  - Loose ligation of a rat's sciatic nerve produces hyperalgesia to thermal stimuli
      and elicits guarding behavior directed at the afflicted paw. The present
      experiments test whether localized inflammation induced by the suture material
      used to ligate the nerve is critical to the development of hyperalgesia. Daily
      injections of dexamethasone reduced the inflammatory response induced by the
      sutures and blocked the development of guarding behavior and thermal
      hyperalgesia. In a second experiment inflammation associated with cotton sutures
      was enhanced by soaking the sutures in Freund's adjuvant prior to ligation. This
      caused an augmentation of thermal hyperalgesia and guarding behavior. These
      results suggest that inflammation around the nerve is critical for the
      development of guarding behavior and thermal hyperalgesia in this model of
      neuropathic pain.

PMID- 7739806
TI  - Early and transient increase of rat hippocampal blood-brain barrier permeability
      to amino acids during kainic acid-induced seizures.
AB  - The effects of kainic acid (KA) induced seizures on the permeability of
      hippocampal blood-brain barrier (BBB) to amino acids were investigated using a
      new method based on the combination of brain microdialysis of alpha
      [3H]aminoisobutyric acid (AIB) and blood sampling. The transfer of AIB through
      the BBB was thus, for the first time, monitored in vivo in awake animals. KA
      administration i.v. produces a rapid and transient increase in hippocampal
      transfer of AIB after the beginning of seizures which is closely correlated to
      epileptic activity. The possible consequences of this increased transport of AIB
      from blood to brain are discussed in relation to previously reported transient
      augmentations of extracellular cerebral glutamate concentrations during KA
      induced epilepsy.

PMID- 7739807
TI  - Anti-NGF treatment blocks the upregulation of NGF receptor mRNA expression
      associated with collateral sprouting of rat dorsal root ganglion neurons.
AB  - The collateral sprouting of intact cutaneous sensory neurons has been shown to be
      dependent upon the presence of nerve growth factor (NGF). We have examined NGF
      receptor (NGFR) mRNA expression in DRG neurons undergoing sprouting and in dorsal
      root ganglion (DRG) neurons whose sprouting had been prevented through exposure
      to anti-NGF antiserum during the course of the experiment. The results indicate
      that the low affinity p75 NGFR mRNA is increased by 4 days post-operatively in
      DRGs from control serum-treated animals, and that this increase is most
      pronounced in smaller neurons. In contrast, the expression of p75 mRNA was
      maintained at control levels in DRGs from anti-NGF-treated animals. Results for
      trkA expression indicate an increase in expression at days 4-6 post-op in both
      groups of animals, with the anti-NGF treatment having a delayed influence on mRNA
      levels. Examination of GAP-43 mRNA levels revealed an increased expression in
      sprouting DRG neurons, whereas this increase was not observed in DRGs from anti
      NGF treated animals. Taken together, these results provide further evidence of
      NGF's role in the collateral sprouting of nociceptive neurons.

PMID- 7739808
TI  - Displacement of norepinephrine by alpha-methylnorepinephrine in the nucleus
      tractus solitarius of the rat.
AB  - Rat brain slices from the dorsomedial medulla containing the nucleus tractus
      solitarius were loaded with [3H]norepinephrine ([3H]NE) for superfusion.
      Electrical stimulation (3 Hz, 25 mA, 1 min) resulted in fractional release ratios
      S2/S1 of 0.97 +/- 0.02 in normal Krebs-Henseleit (KH) and 0.93 +/- 0.06 in the
      presence of 30 microM cocaine. With cocaine in the KH medium, L-alpha
      methylnorepinephrine (alpha-MeNE) significantly reduced the [3H]NE release S2/S1
      without affecting the basal release ratios. Without cocaine in the KH medium both
      0.1 and 1.0 microM alpha-MeNE increased the basal release B2/B1 that was not
      affected by yohimbine. Prazosin had no effect on the S2/S1 ratio but did
      attenuate the basal release effects of alpha-MeNE. In low Ca2+ studies where the
      S2 stimulus was abolished, 1.0 microM alpha-MeNE induced a sharply elevated
      increase in the B2/B1 ratio. It appears that alpha-MeNE in the presence of the
      uptake inhibitors reduces presynaptic neurotransmitter release through alpha 2
      adrenoceptors, whereas when uptake of the monoamines was not blocked alpha-MeNE
      was considerably more efficacious as a displacing agent of neurotransmitter.

PMID- 7739809
TI  - The thymosin beta 4 gene is strongly activated in neural tissues during early
      postimplantation mouse development.
AB  - We studied the temporal and spatial distribution of the mRNA encoding for
      thymosin beta 4 (T beta 4), a small acidic actin-sequestering peptide, during the
      early postimplantation mouse development. Analysis of total embryo RNA
      demonstrated a strong activation of T beta 4 gene after gastrulation and
      coincident with neurulation. In situ hybridization showed that T beta 4 mRNA was
      strongly expressed in the central nervous system and peripheral ganglia,
      paralleling the gradient of neuronal differentiation. An intense signal was also
      observed in intraventricular macrophages and blood vessels. The role of T beta 4
      in mammalian neuroembryogenesis is discussed.

PMID- 7739810
TI  - Detection of 5-HT3R-A, a 5-HT3 receptor subunit, in submucosal and myenteric
      ganglia of rat small intestine using in situ hybridization.
AB  - Physiological and radioligand binding studies have demonstrated the existence of
      5-HT3 receptors in the enteric nervous system. In order to determine if the
      cloned 5-HT3 receptor subunit, 5-HT3R-A, was expressed in the enteric nervous
      system of rats, we have performed in situ hybridization with 33P-labeled cRNA
      antisense probes on sections of rat small intestine. Hybridization was detected
      in both submucosal and myenteric ganglia of the duodenum, jejunum, and ileum.

PMID- 7739811
TI  - Utility of intensely fluorescent cyanine dyes (Cy3) for assay of gap junctional
      communication by dye-transfer.
AB  - Utilization of a class of fluorescent cyanine dyes (Cy3) for the assay of gap
      junctional communication by the dye transfer method was examined. When compared
      with Lucifer Yellow (LY), a commonly used tracer, microinjected Cy3 dye was found
      to yield similar degrees of cell coupling. Blockade of the transfer of both
      tracers by 12-O-tetradecanoylphorbol-13 acetate (TPA), which is known to cause
      closure of communicating channels, confirmed gap junctional mediation of dye
      movement. The fixability of a microinjected amine derivative of Cy3 dye
      demonstrated its compatibility with immunostaining protocols involving
      fluorescein isothiocyanate (FITC)-conjugated reagents. These results together
      with the brilliant fluorescence of Cy3 dyes suggest the potential of Cy3 reagents
      as additional tools to study gap junction function.

PMID- 7739812
TI  - Enhancement of NMDA receptor mediated synaptic potentials of rat hippocampal
      neurones in vitro by thyrotropin releasing hormone.
AB  - The effects of thyrotropin releasing hormone (TRH) on excitatory postsynaptic
      potentials (EPSPs) evoked by electrical stimulation of Schaffer collaterals on
      CA1 neurones of the adult rat hippocampal slice preparation were investigated
      using intracellular recording under current clamp conditions. At resting membrane
      potential and in the presence of extracellular Mg2+, TRH (10-20 microM) largely
      potentiated NMDA receptor-mediated EPSPs while leaving those mediated by non-NMDA
      receptors unaffected. This phenomenon had a brief duration (approximately 2 min)
      and was not accompanied by changes in resting membrane potential or input
      conductance. It is suggested that TRH provided a transient upregulation of
      synaptic responses due to NMDA receptor activation.

PMID- 7739813
TI  - Muscarine, oxazole, imidazole, thiazole, and peptide alkaloids, and other
      miscellaneous alkaloids.

PMID- 7739814
TI  - Polyether ionophores.

PMID- 7739815
TI  - Lignans, neolignans, and related compounds.

PMID- 7739816
TI  - Perioperative myocardial infarction--the uncertainties.

PMID- 7739817
TI  - Biases in estimates from the RNZCGP computer research group.
AB  - AIM: This study aimed to determine whether conclusions drawn in studies using
      data from the computer research group of the Royal New Zealand College of General
      Practitioners (RNZCGP) could be extrapolated to other New Zealand general
      practices. METHOD: Retrospectively collected data on doctor, practice, and
      consultation variables form the study database. The control group comprised a
      random sample of 106 New Zealand general practitioners. The study group were 67
      general practitioners participating in the RNZCGP computer research group.
      Comparisons between groups were based on doctor and practice variables, patient
      demography and morbidity, and number and type of service items observed. RESULTS:
      Study group doctors were more likely to have received post graduate training in
      general practice (p < 0.01) and saw more patients entitled to government
      subsidised health care (p < 0.01). The geographical distribution of the study
      group was skewed with more located in the south of New Zealand. Wide variability
      on most other study parameters was seen among doctors in both groups although
      overall patient morbidity was similar for both groups in the 8612 consultations
      analysed. Computer research group general practitioners reported lower rates of
      patient referral and laboratory investigations, and higher immunisation rates
      than the control group (p < 0.01). CONCLUSION: Although the profile of study
      group general practitioners was different from that of the control group, data
      collected by both groups provided a similar reflection of the morbidity and
      services of New Zealand general practice. Adjustments will be needed for
      extrapolating the results of research from the RNZCGP computer research group
      where the focus of the investigation is referrals from primary care,
      investigations, or immunisations.

PMID- 7739818
TI  - Allergic contact dermatitis to Toxicodendron succedaneum (rhus tree): an autumn
      epidemic.
AB  - AIMS: To document all cases of allergic contact dermatitis (phytodermatitis) due
      to contact with Toxicodendron succedaneum (rhus tree) presenting to a dermatology
      clinic during 1993. METHOD: Case-note review of all cases of phytodermatitis
      attributed to exposure to rhus tree seen during 1993 in a dermatology clinic.
      RESULTS: Twenty cases of phytodermatitis to T succedaneum were reviewed. Eight
      patients were females and 12 males with a bimodal age distribution (ten children
      under age of 15 yr, five adults between 35-45 yr of age). Younger patients
      presented with facial dermatitis reflecting facial contact whilst playing under
      rhus trees. Older patients presented largely with a dermatitis affecting the
      upper limbs reflecting contact whilst gardening (usually pruning). Fifteen out of
      twenty presented during the months of March through May (ie. autumn), with the
      remainder presenting in summer (Dec-Feb). The majority of patients required
      systemic steroids to settle the intense dermatitis. CONCLUSIONS: Phytodermatitis
      to T succedaneum is not uncommon in New Zealand, particularly during the autumn
      months. The clinical presentation varies according to the patient's activity.

PMID- 7739819
TI  - Serum sickness like illness and antimicrobials in children.
AB  - AIM: To determine which antimicrobials are associated with the development of
      serum sickness like reactions in children admitted to hospital in Christchurch.
      METHOD: A retrospective case note review of children admitted with serum sickness
      like reactions over a 10 year period was carried out. 59 children were identified
      and 30 of these were eligible for inclusion in the study. RESULTS: Of the 30
      children with serum sickness like reaction, 19 had received cefaclor alone, six
      penicillin V, two amoxycillin, and one each flucloxacillin cotrimoxazole and
      triacetylolendomycin (TAO). Children received these antimicrobials for 3-10 days.
      CONCLUSION: In this study cefaclor was commonest antimicrobial agent associated
      with the development of serum sickness like reaction. This association should
      receive consideration prior to prescribing cefaclor to children.

PMID- 7739820
TI  - Assessment of the laparoscopic treatment of ectopic pregnancy.
AB  - AIMS: To assess the first 2 years experience of the laparoscopic surgical
      treatment of ectopic pregnancy in a regional referral centre. METHODS: All cases
      of ectopic pregnancy in a 2 year period from August 1991 were evaluated to assess
      the impact on the routine management of this condition. RESULTS: In the first
      year 14 cases were managed by laparoscopic means and took an average operating
      time of mean 73.8 (SD 17.2) minutes compared to mean 69.1 (17.9) minutes in the
      26 cases managed this way in the second year. The 40 patients were hospitalised
      for an average of 1.4 days and 24 stayed one night only. There was no difference
      in operating time between registrars and consultants. The only major complication
      was a patient who required an emergency laparotomy because of continued bleeding.
      When all cases of ectopic surgery were evaluated in the second year, six of the
      32 cases required laparotomy to complete the operation. CONCLUSION: The benefits
      of laparoscopic surgical treatment of ectopic pregnancy dictate that this should
      be employed as first line treatment for all cases of tubal ectopic gestation. Our
      experience suggests that achieving such a service, whilst not without pitfalls,
      should be possible in all gynaecology units provided that staff are motivated and
      that laparoscopic equipment is available.

PMID- 7739821
TI  - Fatal pneumonia due to Legionella bozemanii serogroup 1 in a patient with occult
      malignant lymphoma.

PMID- 7739822
TI  - Methadone maintenance treatment: coming of age in New Zealand.

PMID- 7739823
TI  - Human immunodeficiency virus infection and fitness to fly.

PMID- 7739824
TI  - Core services and cardiac surgery.

PMID- 7739825
TI  - Recovery from the effects of sexual abuse.

PMID- 7739826
TI  - Idiopathic CD4+ T-lymphocytopenia: case report.

PMID- 7739827
TI  - Inappropriate request for breast examination.

PMID- 7739828
TI  - Inappropriate request for breast examination.

PMID- 7739829
TI  - The impact of the Bosnian conflict on New Zealand.

PMID- 7739830
TI  - Anaesthesia for carotid endarterectomy.

PMID- 7739831
TI  - Health research in the South Pacific area.

PMID- 7739832
TI  - Necrotising fasciitis and NSAIDs.

PMID- 7739833
TI  - Necrotising fasciitis and NSAIDs.

PMID- 7739834
TI  - Medical ethics: what we couldn't possibly learn at our mother's knee.

PMID- 7739835
TI  - Absence of end-diastolic flow velocity in the umbilical artery: a review.
AB  - The objective of this review was to find the clinical relevance of the absence of
      end-diastolic flow velocity in the umbilical artery. Search was conducted through
      MEDLINE using unabridged MEDLINE Knowledge Finder (Aries System Corp., North
      Andover, MA). All the manuscripts published in English language within last 10
      years (1983-1992) were included in the review process. There has been no report
      of umbilical artery absent-end diastolic velocity before 1983. It was extremely
      difficult to draw a conclusion because a majority of the available reports in the
      literature are either case reports or retrospective analyses. However, for the
      practical purposes it can be concluded that after viability these pregnancies
      should be followed by intense (daily) fetal well-being surveillance with
      conventional antenatal tests. Those who improve their end-diastolic velocity
      should be allowed to continue the pregnancy as long as antenatal testing is
      promising. Persistence of absent end-diastolic velocity may be an indication for
      delivery at a gestational age when there is reasonable chance of survival.
      Cytogenetic evaluation and anatomical survey of these fetuses by ultrasound is
      recommended. Long-term follow up of surviving infants needs to be studied. It is
      impossible for a single institution to accumulate enough cases for adequate
      outcome evaluation. A randomized prospective trial to assess the management of
      pregnancies with absent end-diastolic velocity in the umbilical artery would be
      difficult. Some might even consider such a study unethical. Until such a study is
      performed, an international registry would be helpful for collecting data about
      the perinatal outcomes and management of such patients.

PMID- 7739836
TI  - Cervical carcinoma associated with pregnancy.
AB  - Because of the uncommon synchronous occurrence of pregnancy and invasive cervical
      carcinoma, this disease entity remains poorly understood. In addition
      inconsistent reporting has precluded meaningful meta-analysis. About 1 in 2000
      pregnancies are associated with cervical cancer and pregnancy is a complication
      in approximately 3 percent of patients with cervical cancer. There is little
      evidence to suggest that the pregnancy has an influence on prognosis. Although
      not firmly established, vaginal delivery may have an adverse effect on outcome.
      Timing of delivery must be individualized inasmuch as there is a role for
      delaying treatment in order to achieve fetal lung maturity. Surgery and
      radiotherapy should be utilized in the same stage-dependent manner as in
      nonpregnant patients but management should be individualized and undertaken by a
      multidisciplinary team. These and other issues are discussed more fully in this
      review.

PMID- 7739837
TI  - Fetal akinesia.
AB  - Normal fetal growth and development during pregnancy is highly dependent upon
      adequate fetal movement. Limitation of movement, regardless of the underlying
      cause, can result in a particular pattern of abnormal fetal morphogenesis. This
      phenotype is termed the fetal akinesia deformation sequence (FADS). The etiology
      of fetal akinesia may be generally classified into one of five categories:
      neuropathy, myopathy, restrictive dermopathy, teratogen exposure, or restricted
      movement due to intrauterine constraint. In this article, the differential
      diagnosis of fetal akinesia is systematically reviewed and information regarding
      prenatal diagnosis, prognosis, perinatal management, and recurrence risks are
      discussed.

PMID- 7739838
TI  - Indoor air quality cases require detective-like analyses of facts.

PMID- 7739839
TI  - Getting the greatest bang for the buck.

PMID- 7739840
TI  - Decontamination matrix helps assess reuse potential for protective clothing.

PMID- 7739841
TI  - A law for all.

PMID- 7739842
TI  - Don't reward the safety cover-up.

PMID- 7739843
TI  - Histological study of the circulatory system of human dental pulp from
      individuals under local anesthesia and electro-acupuncture.
AB  - A transmission electron microscopic (TEM) study was conducted on dental pulp
      obtained from patients under acupuncture or infiltration local analgesia. It was
      difficult to differentiate lymphatic circulation in the dental pulp that received
      infiltration anesthesia, because the vessels were constricted, congested, and
      showed stasis and thrombosis. On the other hand, the dental pulp that received
      acupuncture showed normal arterioles, capillaries, and venules, as well as some
      lymph capillaries and small efferent lymphatic vessels that measured about 8
      microns and 100 microns in diameter, respectively. The lymphatic endothelial
      walls had many intercellular gaps, an imperfect basal lamina, and a few
      discontinuous pericytes. Between the openings in the lymphatic vessels, there
      were bundles of junctional filaments extending towards the dental pulp connective
      tissue. Therefore, the lymphatic system, which contains mainly B-3-alpha
      capillaries, is a leaky tissue for regulating fluid in the dental pulp.

PMID- 7739844
TI  - A Golgi study on the nucleus sphericus of the striated snake, Elaphe
      quadrivirgata.
AB  - The intrinsic organization of the nucleus sphericus (NS) was studied in the
      striated snake using the rapid Golgi method. The NS is a large aggregation of
      cells located in the posterior portion of the telencephalon and is, as a whole,
      cup-shaped with its hilus oriented in the rostral direction. From the periphery
      inward, the following three concentric layers were discernible: a marginal layer,
      mural layer and hilar layer. The marginal layer consists of scattered cells
      extending dendrites internally toward the hilar layer and externally into the
      anterior commissure (AC). The mural layer contains densely packed polygonal
      neurons with dendrites extending internally into the hilar layer and externally
      toward the marginal layer. The hilar layer consists of scattered cells whose
      dendrites extend in a transverse direction, distributing mainly in the hilar
      layer. The axons of the neurons in the marginal and mural layers travel
      rostromedially, and some axons can be traced into the AC, while those of the
      neurons in the hilar layer run rostrally, and some are lost among fibers of the
      accessory olfactory tract (AOT). The afferents to the NS are derived mainly from
      the AOT and AC. The AOT fibers travel caudally in a thick bundle through the
      hilus and are distributed totally within the hilar layer, forming a dense fiber
      plexus. The AC fibers enter the nucleus from the rostromedial aspect and run in
      an arched course, emitting numerous fine short collaterals.

PMID- 7739845
TI  - Anatomical studies on the extensor pollicis et indicis accessorius muscle and the
      extensor indicis radialis muscle in Japanese.
AB  - Anatomical studies on the extensor pollicis et indicis accessorius and extensor
      indicis radialis muscles were conducted on 952 upper limbs from 476 Japanese
      adult cadavers. Each anomalous muscle occurred between the extensor pollicis
      longus proprius and extensor indicis proprius muscles in the dorsum of the
      forearm and hand. The extensor pollicis et indicis accessorius muscle was present
      in 13 of the limbs (1.4%). It was not coexistent with another anomalous muscle of
      the extensor digitorum profundus mass in 9 cases, and it was coexistent with that
      muscle in 4. The extensor indicis radialis muscle was present in 34 limbs (3.6%).
      It was accompanied by another anomaly of the extensor digitorum profundus mass in
      5 cases, and not accompanied by that muscle in 29. The extensor pollicis et
      indicis accessorius and extensor indicis radialis muscles were innervated by the
      posterior interosseus nerve of the radial nerve. It seems that the former
      anomalous muscle supplies the extensor control of the thumb and index finger, and
      the latter one of the index finger only. Each anomalous muscle was considered to
      be differentiating on the radial side of the extensor digitorum profundus mass in
      humans.

PMID- 7739846
TI  - Immunocytochemical localization of estrogen and progesterone receptors (ER & PgR)
      in breast cancer.
AB  - The localization of estrogen receptors (ER) and progesterone receptors (PgR) in
      human breast cancer was examined light and electron microscopically by using
      specific monoclonal antibodies. Among the breast cancer patients, ER-positive
      (ER[+]) cases were shown by enzyme immunoassay (EIA) to account for 58.9%
      (63/107), and 63.5% of these cases were women in the postmenopausal state. The
      PgR-positive (PgR[+]) rate was 50.5% (54/107), with 44.4% of these positive cases
      being postmenopausal women. The rates of ER(+) and PgR(+), ER negative (ER[-])
      and PgR negative (PgR[-]), and ER(+) and PgR(-) cases were 43.9% (47/107), 34.6%
      (37/107) and 15.0% (16/107), respectively. Although ER(-) and PgR(+) cases were
      in few number, they were found (6.5%, 7/107). These results correlated well with
      those obtained by the immunocytochemical method. In either case, i.e anti-ER or
      anti-PgR reaction, positive nuclei and negative nuclei were found intermingled
      with each other in a given visual field. In electron microscopy, both anti-ER and
      anti-PgR antibodies bound to sites in the euchromatin area of the nucleus.

PMID- 7739847
TI  - Enzyme cytochemical study of alkaline phosphatase in rat hepatocytes--change of
      location after colchicine administration or bile duct ligation.
AB  - Changes in location of alkaline phosphatase (ALP) in rat hepatocytes after two
      different treatments were examined by the enzyme cytochemical technique. Although
      reaction deposits which indicate ALP activity were observed mainly in the bile
      canalicular membranes until 6 hr after colchicine administration, they were
      present not only in the bile canalicular membranes but also in the sinusoidal and
      lateral membranes 12 hr after drug administration. Eighteen and 24 hr after
      colchicine administration, a large number of reaction deposits were seen in the
      sinusoidal membranes and in the mutual membranes between adjacent hepatocytes,
      where the bile canaliculi were completely deformed and complex interdigitations
      appeared. On the other hand, after bile duct ligation, reaction deposits appeared
      in every domain of the plasma membranes. Twenty-four hr after colchicine
      administration to bile-duct-ligated rats, an increase in the number of the
      reaction deposits was observed, but the location of ALP remained unchanged. The
      present study suggests that intracellular transport and location of ALP in
      hepatocytes may be controlled by a common mechanism in colchicine-treated and
      bile-duct-ligated rats.

PMID- 7739848
TI  - Three-dimensional structure of the perimysium in sternocleidomastoid muscle.
AB  - The morphology of the sternocleidomastoid muscle (SCM) of human fetuses, ranged
      from 12 to 32 weeks gestation, was investigated by a light microscopy and a
      scanning electron microscopy. The collagenous fibers of the perimysium of the SCM
      formed complex structures from 24 weeks gestation by contrast to fibers of the
      endomysium of the SCM. The cross-sectional area (CSA) of the bundle of muscle
      fibers and the CSA of the individual muscle fibers of the SCM increased during
      development from 12 to 32 weeks gestation, in a process linked to the development
      of the perimysium. Therefore the perimysium affects and controls to the muscle
      fiber of the developed SCM and acts to resisting stretch forces in the movements.
      The changes in the arrangement and development of the collagenous fibers in the
      perimysium may be correlated to with these of the muscle fibers.

PMID- 7739849
TI  - Approach to combine confocal laser scanning microscopy with casting techniques of
      SEM.

PMID- 7739850
TI  - [New lasers in dermatologic surgery].
AB  - Developments in the fields of laser technology and application have significantly
      broadened its clinical use over the past two decades. As lasers became more
      smaller, more reliable and less expensive, dermatology will benefit new laser
      based therapeutic and diagnostic methods. Relevant laser systems and their
      clinical applications are presented, as are investigational laser systems, which
      may be of importance for the future in dermatology. We review advances in the use
      of pulsed lasers for treating vascular and non-vascular, pigmented epidermal and
      dermal lesions, for precise cutting of tissue, for photodynamic therapy and the
      future role of diode lasers in dermatological laser surgery is also discussed.

PMID- 7739851
TI  - [Diagnostic value of the study of caffeine elimination in chronic liver
      diseases].
AB  - Data from the past few years have shown that as caffeine metabolizes solely in
      the liver, caffeine elimination can serve as a liver function test. We have
      collected data by monitoring 40 persons with liver diseases (11 chronic alcoholic
      hepatitis, 24 liver cirrhosis, 5 non-cirrhotic liver disease). Eight subjects
      served as controls. The patients with liver cirrhosis were classified according
      to the Child--Pugh scoring system. To determine caffeine elimination blood
      samples were collected before and at 3, 6, 9 and 12 hours after oral
      administration of 0.2 g caffeine. Fasting serum caffeine concentration and
      concentration 12 hours after administration, serum clearance, half life, peak
      concentration and volume of distribution have been compared. The respective
      values measured in patients with non-cirrhotic liver diseases did not differ
      significantly from the controls. The disappearance of caffeine was significantly
      decreased in cirrhotics. Our results demonstrated a good correlation between
      impairment of caffeine elimination and assessment of severity of liver disease by
      the Child--Pugh classification. Measuring serum levels in samples taken 12 hours
      after caffeine administration is a simple and useful method in the diagnosis of
      liver diseases at cirrhotic stage.

PMID- 7739852
TI  - [Treatment of ectopic pregnancy by transvaginal ultrasonography-guided puncture
      and local application of methotrexate].
AB  - The early detection of ectopic pregnancy--using transvaginal sonography, beta
      human chorionic gonadotropin determination in blood and laparoscopy--allow us to
      perform conservative therapeutic approaches to preserve future fertility. The
      authors report their experiences on five patients treated by local administration
      of methotrexate. The drug was injected to the ectopic gestational sac by
      transvaginally performed, sonographically directed puncture. The technique of the
      method, the criteria of selection and follow-up of patients have been discussed.
      Giving an overview on the other conservative methods, their increasing role is
      suggested in the management of early ectopic pregnancies.

PMID- 7739853
TI  - [Strength-giving self-deception during recovery--non-disclosure and lying as part
      of medical treatment].

PMID- 7739854
TI  - [Syncumar-induced necrosis following heparin-induced thrombocytopenia and
      thrombosis].
AB  - The authors describe the combined occurrence of heparin-induced thrombocytopenia
      and cumarin-induced skin necrosis, a rare condition that has not yet been
      reported in Hungary. The 69-year-old woman had received prophylactic heparin
      treatment prior to total hip arthroplasty. The first complication that the
      anticoagulant therapy brought about was serious thrombocytopenia paradoxically
      associated not with bleeding but with deep vein thrombosis. The latter
      necessitated coumarin therapy which resulted in severe skin necrosis.

PMID- 7739855
TI  - [In memory of Janos Hillinger].

PMID- 7739856
TI  - [Preface to the treatise De Humani Corporis Fabrica, by Andreas Vesalius].

PMID- 7739857
TI  - The history and development of the implantable hearing aid.
AB  - Implantable hearing aids have an interesting and colorful history. These devices
      have usually been investigational, but this has changed. Currently, several
      implantable devices are available for ongoing clinical trials in humans. They
      have promise in providing improved hearing in certain cases of conductive, mixed,
      and sensorineural hearing loss.

PMID- 7739858
TI  - Ongoing investigations into an implantable electromagnetic hearing aid for
      moderate to severe sensorineural hearing loss.
AB  - Over 20 million Americans have a hearing loss that produces problems in
      communication. The majority of these hearing-impaired individuals would benefit
      from conventional hearing aids, yet only about 15% use amplification devices.
      Many of the reasons for the lack of use of conventional hearing aids can be
      resolved by an implantable middle ear device directly coupled to the ossicular
      chain. This article presents the advantages of the implantable middle ear device.

PMID- 7739859
TI  - Contactless semi-implantable electromagnetic middle ear device for the treatment
      of sensorineural hearing loss. Short-term and long-term animal experiments.
AB  - A contactless electromagnetic hearing device has been designed following basic
      science experiments, improvement of electronics, and precision micromechanics.
      Different prototypes have been developed and tested in the laboratory, fresh
      human temporal bones, and acute and chronic animal experimentation. A conductive
      hearing loss model was first developed in the cat using samarium cobalt as the
      target magnet. Later, a highly efficient electromagnetic air-core coil was
      selected to vibrate a neodymium iron boron magnet cemented to the body of the
      incus and tested in acute and chronic experiments using the cat as the model. In
      this group of animals, the ossicular chain was left intact. There was no failure
      of the target magnet, driving coil, or implanted electronics. The only problem
      encountered in this evaluation was a malfunction of the receiving antenna that
      had to be redesigned and retrofitted into the implanted units. This system would
      be suitable for the treatment of moderate to severe sensorineural hearing loss.
      Planning to begin human clinical trials is ongoing.

PMID- 7739860
TI  - Current status and future of implantable electromagnetic hearing aids.
AB  - Partially implantable electromagnetic hearing aids have several potential
      advantages over conventional hearing aids. As conventional hearing aids improve
      in the quality of sound they deliver, however, the role of implant aids must be
      redefined. One area where they may provide the most benefit is in patients with
      moderate to severe hearing loss.

PMID- 7739861
TI  - The implantable hearing device for sensorineural hearing impairment. The Hough
      Ear Institute experience.
AB  - This article describes one group's experience in developing and implanting rare
      earth magnets for conductive hearing loss and also for sensorineural hearing
      loss. Success and failures from over a decade of work are highlighted.

PMID- 7739862
TI  - Electromagnetic ossicular augmentation device.
AB  - Conventional hearing aids have a number of limitations inherent to amplifying
      sound in the narrow confines of the external auditory canal. Disadvantages
      include acoustic feedback, poor fidelity, and the stigmata of aging. Since 1986,
      Michigan Ear Institute and Smith and Nephew Richards Company have been
      investigating the feasibility of a new device that converts sound to an
      electromagnetic field. The efficacy and safety of electromagnetic-induced hearing
      was sufficient enough to have the Federal Food and Drug Administration approve a
      pilot study of ten patients with a sensorineural hearing loss in whom a target
      magnet is implanted beneath the tympanic membrane. A status report of this study
      and a review of our preceeding investigations are presented in this article.

PMID- 7739863
TI  - Selection of biomaterials for middle and inner ear implants.
AB  - In the selection of biomaterials for middle ear applications of implantable
      devices, certainly the site of implantation and the mass of the implant will
      dictate the choice of biomaterials. Hermetic sealing of an implant is best
      achieved by the use of metals, not polymers. Osteocompatibility of an ossicular
      implant can be enhanced by the incorporation of calcium phosphates such as
      hydroxyapatite coatings. Finally, osseointegration or osseofixation is neither
      necessary nor desirable for ossicular implants, because (1) they may need to be
      removed or replaced in the future and (2) their solid fixation to an ossicle is
      not necessary for the vibratory function of hearing amplification.

PMID- 7739864
TI  - Piezoelectric middle ear implant preserving the ossicular chain.
AB  - The authors developed a research program on piezoelectric middle ear implants. A
      piezoelectric vibrator was implanted on guinea pigs, enabling piezoelectric
      auditory-evoked recording. The shape and sizes of a vibrator for humans were
      determined by a human temporal bone study. These human-type vibrators showed good
      performances in vitro. A particular vibrator for humans that can be implanted on
      the stapes' head, without irreversibly interrupting the ossicular chain, was
      designed by the authors.

PMID- 7739865
TI  - The round window electromagnetic implantable hearing aid approach.
AB  - The round window electromagnetic implantable hearing aid (RWEM) approach uses a
      magnet surgically implanted onto the round window membrane of the cochlea to
      impart vibrational energy to the inner ear when driven by a nearby
      electromagnetic coil. In this article, experimental methods used in animal ABR
      studies are described for this approach and evidence for the viability of this
      technique is demonstrated by the similarity of ABR waveforms obtained using RWEM
      and acoustically-evoked stimuli.

PMID- 7739866
TI  - Acoustic stimulation of the semicircular canals.
AB  - Stimulation of the semicircular canals provides an alternative method of
      vibratory stimulation of the auditory system. The frequency response
      characteristics of stimulation of the tympanic membrane, malleus, stapes, round
      window, and fenestrated semicircular canal are presented in this article.

PMID- 7739867
TI  - Engineering principles of mechanical stimulation of the middle ear.
AB  - This article presents the transducer principles of possible middle ear hearing
      devices with their characteristics and selection considerations summarized. The
      frequency response and the needed force and displacement at the ossicular chain
      sites were measured to determine approximately the system requirements and design
      considerations. The power required to vibrate the ossicular chain is estimated to
      be of the order of 0.1 watt, which is three orders of magnitude smaller than the
      power consumption of devices being developed in various laboratories. Careful
      engineering design and evaluation is needed. A design example of the transducer
      used with a partially implantable, noncontact electromagnetic hearing device is
      presented in this article with laboratory evaluation results.

PMID- 7739868
TI  - Long-term results for the Xomed Audiant Bone Conductor.
AB  - The Audiant Bone Conductor is now used worldwide. Results consistently
      demonstrate that when used on patients within the recommended criteria, hearing
      thresholds are improved to within 10 dB of the preoperative bone conduction
      threshold. In this article, comparisons are made with the reported results of the
      Audiant versus other comparable bone conduction devices, or with surgical
      procedures for conditions such as congenital aural atresia.

PMID- 7739869
TI  - The bone-anchored hearing aid. Design principles, indications, and long-term
      clinical results.
AB  - This article presents a summary of design principles, indications, and clinical
      results obtained with the bone-anchored hearing aid (BAHA). Hearing through bone
      conduction and mechanical stimulation of the skull with percutaneous versus
      transcutaneous excitation and the functional capability of the ear level BAHA
      sound processor is presented. Moreover, the surgical procedure is described and
      the success rate to establish and maintain osseointegration is presented together
      with the frequency of skin reactions at the implant site. The audiologic and
      questionnaire results achieved with the BAHA is also presented and discussed.

PMID- 7739870
TI  - The bone-anchored hearing aid compared with conventional hearing aids. Audiologic
      results and the patients' opinions.
AB  - The bone-anchored hearing aid (BAHA) was evaluated in 65 patients by comparing
      speech recognition and questionnaire results with those obtained with the
      patients' own previous hearing aids. In the majority of patients who previously
      used a conventional bone conductor, significantly improved speech recognition
      scores were found with the BAHA. The majority preferred the BAHA to their
      previous bone conductors. For the patients who previously used air conduction
      hearing aids but had to stop because of chronic draining ears, the results were
      ambiguous. Nevertheless, the BAHA seems to be the best solution for this subgroup
      as well. It is concluded that the BAHA is a valuable addition to the
      audiologists' tools.

PMID- 7739871
TI  - Partially implantable hearing aid using piezoelectric ceramic ossicular vibrator.
      Results of the implant operation and assessment of the hearing afforded by the
      device.
AB  - The aim of designing an implantable hearing aid (IHA) is to compensate for some
      of the disadvantages of conventional hearing aids. The IHA described in this
      article is a direct oscillation type in which the piezoelectric ceramic ossicular
      vibrator coupled directly to the stapes transmits sound signals to the perilymph
      effectively. This type of IHA can give a better fidelity of sound perception than
      a conventional hearing aid.

PMID- 7739872
TI  - Partially implantable piezoelectric middle ear hearing device. Long-term results.
AB  - In accordance with the 1992-1993 Japanese government approval of production and
      implementation in the health insurance system of the partially implantable
      piezoelectric middle ear device (P-MEI), we are conducting follow-up studies on
      the implanted patients. This article reports the results of the 16 cases, which
      are regarded as successful implantations because these patients are using the
      device every day as long as they are awake. A successful case is presented to
      illustrate the efficacy of the device.

PMID- 7739873
TI  - [Perisinusoidal stellate cells or Ito cells and their role in hepatic fibrosis].
AB  - In this review on stellate cells, discovered by Kupffer more than 100 years ago,
      morphological and ultrastructural aspects, origin and differentiation are
      described through also a comparative analysis in some animal species. Many
      methods used from different laboratories for isolation, identification and in
      vitro culture of these heterogeneous cells are reported and discussed regarding
      advantages and disadvantages. The normal Ito cells functions, that are metabolism
      and storage of vitamin A, extracellular matrix (ECM) synthesis under cytokines
      control, and sinusoidal tonus through its reversible contraction are discussed.
      Then an update description is reported about fibrogenesis and all the factors
      involved in liver fibrosis, from cytokines to the adhesion molecules. Stellate
      cells being the main source of ECM in chronic liver injury, can play different
      and primary roles by shifting its functions toward fibrosis. The role of
      metalloproteinases and their inhibitors on the balance of the ECM synthesis and
      degradation are also evaluated. When liver is injured, Ito cells became activated
      and change their phenotype from fat-storing cells to cells to cell devoid of
      retonoid droplets. They express the smooth muscle-like features, including a-SM
      actin. The role of vitamin A in liver fibrosis is not yet clear: current data and
      hypothesis about this topic are discussed. Contractile behaviour of the
      perisinusoidal stellate cells seems also important in influencing portal blood
      pressure during fibrosis and cirrhosis. Diagnostic methods for hepatic fibrosis
      and Ito cells activation are also briefly reported. The review is supplied with
      more than three hundred references updated to August 1994.

PMID- 7739874
TI  - Detection of human herpesvirus-6 and Epstein-Barr virus genome in childhood
      Hodgkin's disease.
AB  - Two widespread human herpesviruses, the Epstein-Barr virus (EBV) and the Human
      Herpesvirus 6 (HHV-6), have been frequently associated with Hodgkin's Disease
      (HD) and, recently, it has been observed an HHV-6 transactivation effect on EBV
      replicative cycle. We studied the presence and the possible association between
      EBV and HHV-6 in childhood HD cases, nodular sclerosis subtype. We analyzed
      formalin-fixed and paraffin-embedded lymph nodes from 15 cases by PCR for HHV-6
      genome, and by PCR and in situ hybridization (ISH) for EBV genome. One out 15
      samples resulted positive for HHV-6 DNA PCR, while 5 resulted positive for EBV
      DNA PCR. Only one sample positive for HHV-6 resulted positive for both HHV-6 and
      EBV genome. All samples were negative in ISH. At the moment, it is not clear the
      exact role of EBV and HHV-6 in the lymphomagenesis, neither it is possible to
      establish the rate of their interaction; our data show that it does not exist in
      vivo an evidence of their association.

PMID- 7739875
TI  - [Primary CD30+ large-cell non-Hodgkin's lymphoma of the soft tissues. Clinico
      pathologic study of a case].
AB  - The authors report a single case of primary soft tissue CD30+ non anaplastic non
      Hodgkin's lymphoma. The clinical, histological and immunohistochemical features
      of this peculiar lymphoma type are discussed. Within extranodal lymphomas, a
      primary soft tissue involvement is rare and the literature lacks exhaustive data
      on the clinical behaviour of these malignancies. In our case, the prognosis
      appeared more closely related to the clinical stage of the disease than to
      histology.

PMID- 7739876
TI  - Glomus tumour: the immunohistochemical characteristics of twenty-three cases.
AB  - Twenty-three cases of glomus tumour were investigated with the antibodies
      keratin, vimentin, neurofilaments, desmin, actin, S100, Factor VIII-related
      antigen, substance P and KP1/CD68. It will be shown that the glomus cells were
      vimentin-positive in 11 out of 23 cases (48%), actin-positive in 16 out of 23
      cases (70%) and desmin-positive in 9 out of 23 cases (39%). The KP1 monoclonal
      antibody demonstrated the presence of numerous mast cells in some cases. The
      substance P was only occasionally positive in six cases (26%). No positive
      staining was seen with keratin, neurofilaments, S100 and Factor VIII-related
      antigen. It is confirmed that glomus cells can be considered as elements of
      smooth muscle origin. Our study suggests a possible explanation of the mechanism
      which induces paroxysmal attacks in patients with glomus tumours.

PMID- 7739877
TI  - [Bronchiolo-alveolar carcinoma]. Histologic analysis of 3 cases, one of which
      with ultrastructural study].
AB  - A histological analysis was performed on 3 cases of bronchiolo-alveolar carcinoma
      (BAC) in one of which an electronmicroscopic research was made. It was about a
      case of BAC with pneumonocytes of type I the lasting in life of which from the
      ascertainment of the tumor was 1.2 years (autopsy); and of a case of BAC with
      pneumocytes of type II (operatory case) and of a case of BAC with conventional
      cells (autoptic case) who survived an average of 4.3 years. All the cases had
      metastasis in the ilar lymph nodes. The three BAC were localized in the
      superficial area of the lung and it is also evident that they occupy the alveolar
      cavities, taking the thin alveolar wall as the only interstice. Besides in the
      following development there was evident tendency to hypertrophy of the
      interstizial collagen tissue, in the BAC with pneumocytes of type II and
      respectively with cells of conventional type; and the subtotal PAS negativity in
      the BAC with pneumocytes of type I. The included nuclears present in the only BAC
      with pneumocytes of the second type take the origin from the cytoplasm in the
      shape of small round masses penetrating into the nucleus, as from electronic
      microscopy. In the considered BAC, it was about surfactant apoproteins wich, in
      the nucleus, precipitate in morphologically different shapes.

PMID- 7739878
TI  - [Thyroid pathology: evaluation of the average value of NORs and its potential
      diagnostic and prognostic application].
AB  - Argyrophilie technique to identify nucleolar organizer regions (NORs) applied in
      formalin-fixed paraffin sections of thyroid tissue allow us to reveal NORs as
      block dots in the nuclei of cells. In the present study the relationship between
      number of NORs and cellular activation emphasize significant statistical data: it
      was found that the number of AgNORs in malignant thyroid lesions significantly
      exceeded those of benign thyroid lesions. This objective assessment associated
      with easily method show an advantage in thyroid diagnostic histopathology an
      adjunct to routine methods.

PMID- 7739879
TI  - [Human dirofilariasis in southern Italy. I. The Puglia Region].
AB  - Nine new cases of human Dirofilariasis by Dirofilaria repens, in subjects living
      in Apulia, aged 30 to 60 years, are reported. Six were subcutaneous and three
      subconjunctival. Many of them occurred a number of years ago and were identified
      thanks to a specific joint investigation carried out by a parasitologist, some
      histopathologists and ophthalmologists. Of special relevance is one subcutaneous
      case with contemporary presence of 2 nodules in different regions of the body
      (mamma and forearm) and another subconjuctival case with strong inflammatory
      reaction (episcleritis, chemosis, orbital cellulitis) associated with the passage
      of the nematode under the Tenon's capsule.

PMID- 7739880
TI  - [Human dirofilariasis in southern Italy. II. The Calabria Region].
AB  - A new case of subcutaneous Human Dirofilariasis, in a 42-year-old woman from the
      province of Cosenza, is described. It is the first reported in Calabria. The
      nematode, an immature female of Dirofilaria repens, was clinically diagnosed as a
      "Fibrolipoma". In a collateral research on dogs in different areas of the same
      province, microfilariae of D. repens in 2 out 134 individuals were detected.

PMID- 7739881
TI  - [Lymph-node inflammatory pseudotumor with granulomatous component. Report of a
      case and review of the literature].
AB  - A case of inflammatory pseudotumor of lymph node in a 65 year-old man is
      described. The case is striking because of a granulomatous component within the
      lesion, a finding unpreviously described. This lesion, benign by nature, should
      not be misinterpreted as a neoplastic process, especially lymphomas or soft
      tissue tumors; problems related to the differential diagnosis are also discussed.

PMID- 7739882
TI  - [Lymph node myofibroblastoma: report of a submandibular case with peculiar
      morphologic and immunohistochemical characteristics].
AB  - The Authors describe a case of intranodal myofibroblastoma presenting in the
      submandibular region as a firm, indolent and freely mobile rounded nodule of
      about 3 cm. in diameter. The nature of this uncommon benign lesion is discussed.
      The observed histological features are partly different from the cases originally
      described. A proliferation of moderately pleomorphic spindle cells, which are
      vimentin and muscle specific actin positive, occupies a large part of a lymph
      node, sharply separated from the normal tissue. The so called "amianthoid fibres"
      are however absent and the inflammatory cells are almost exclusively eosinophils,
      mainly localized at the border between the lesion and the residual lymph node.
      Some spindle cells also show an unexplained positivity for the S-100 protein. In
      addition, extranodal extension of inflammation with few spindle cells is present.
      Such a complex picture has many features in common with the inflammatory
      pseudotumor of lymph node, another benign cause of lymphadenopathy. For this
      reason, the Authors suggest the possibility that myofibroblastoma is not a true
      neoplasm, but, together with the inflammatory pseudotumor, a peculiar type or a
      different stage of an abnormal lymph node reactivity.

PMID- 7739883
TI  - Primary bronchial malignant melanoma. A case report.
AB  - A case of primary bronchial malignant melanoma occurred in a 66 years old woman
      is reported. Because of cough and hemoptysis bronchoscopic examination was
      performed and and a polypoid mass was found to occlude the right lower bronchus.
      Histopathologic examination showed the presence of malignant melanoma also
      confirmed by immuno reactivity with antibodies to S-100 protein and melanoma
      associated monoclonal antibody HMB45. Clinical history, physical examination and
      other instrumental investigations failed to find other possible primary sites of
      the tumour. Primary melanoma of the lung is a very rare condition, but our case
      seems to satisfy the criteria to be considered in the little group of definite
      primary melanoma of the lower respiratory tract.

PMID- 7739884
TI  - [Signet ring cell carcinoma of the rectum in a 15-year-old youngster].
AB  - Primary colonic signet ring cell carcinoma is a rare neoplasia. The prognosis is
      particularly poor with only very few patients surviving more than one year
      following diagnosis. We report a case of primary signet ring cells carcinoma of
      the rectum, detected in a 15 year old young male, particularly interesting for
      the patient young age and for good prognosis.

PMID- 7739885
TI  - Giant cell reparative granuloma of the maxillary bone: case report and review of
      diagnostic criteria.
AB  - This paper reports a case of giant cell reparative granuloma of the right
      maxillary bone of a 13-year-old caucasian girl. It may be very difficult to
      distinguish this entity from other lesions of mandible, maxilla and skull bones
      which contain multinucleated giant cells. The differential diagnosis, especially
      from giant cell tumors of the bone, is discussed. Accurate diagnosis lies on
      correct integration of clinical, radiographical and histopathological data.

PMID- 7739886
TI  - Bilateral interstitial cell tumor of the testis: a report of a case in an adult.
AB  - We describe a case of metachronous bilateral interstitial-cell tumor of the
      testis in a 54-year-old man with no evidence of endocrine symptoms. About 300
      Leydig cell tumor cases have been reported in literature and only in 3% the tumor
      was bilateral. Rare examples have been reported in cryptorchid testis. In adult
      patients with Leydig cell tumor of the testis, endocrinologic signs occur in 20
      per cent of cases and often precede the onset of a palpable testicular mass.
      Pathological aspects are discussed and a survey of the literature is reported.

PMID- 7739887
TI  - [V Meeting of Ultrastructural Diagnosis. Borgio Verezzi, 27 May 1994. Abstracts].

PMID- 7739888
TI  - Ciliate telomerase RNA structural features.
AB  - Telomerase RNA is an integral part of telomerase, the ribonucleoprotein enzyme
      that catalyzes the synthesis of telomeric DNA. The RNA moiety contains a
      templating domain that directs the synthesis of a species-specific telomeric
      repeat and may also be important for enzyme structure and/or catalysis.
      Phylogenetic comparisons of telomerase RNA sequences from various Tetrahymena
      spp. and hypotrich ciliates have revealed two conserved secondary structure
      models that share many features. We have cloned and sequenced the telomerase RNA
      genes from an additional six Tetrahymena spp. (T. vorax, T. borealis, T.
      australis, T. silvana, T. capricornis and T. paravorax). Inclusion of these
      sequences, most notably that from T. paravorax, in a phylogenetic comparative
      analysis allowed us to more narrowly define structural elements that may be
      necessary for a minimal telomerase RNA. A primary sequence element, positioned 5'
      of the template and conserved between all previously known ciliate telomerase
      RNAs, has been reduced from 5'-(C)UGUCA-3' to the 4 nt sequence 5'-GUCA-3'.
      Conserved secondary structural features and the impact they have on the general
      organization of ciliate telomerase RNAs is discussed.

PMID- 7739889
TI  - Discordant expression and variable numbers of neighboring GGA- and GAA-rich
      triplet repeats in the 3' untranslated regions of two groups of messenger RNAs
      encoded by the rat polymeric immunoglobulin receptor gene.
AB  - An unusual S1-nuclease sensitive microsatellite (STMS) has been found in the
      single copy, rat polymeric immunoglobulin receptor gene (PIGR) terminal exon. In
      Fisher rats, elements within or beyond the STMS are expressed variably in the 3'
      untranslated regions (3'UTRs) of two 'Groups' of PIGR-encoded hepatic mRNAs (pIg
      R) during liver regeneration. STMS elements include neighboring constant regions
      (a 60-bp d[GA]-rich tract with a chi-like octamer, followed by 15 tandem d[GGA]
      repeats) that merge directly with 36 or 39 tandem d[GAA] repeats (Fisher or
      Wistar strains, respectively) interrupted by d[AA] between their 5th-6th repeat
      units. The Wistar STMS is flanked upstream by two regions of nearly contiguous
      d[CA] or d[CT] repeats in the 3' end of intron 8; and downstream, by a 283 bp
      'unit' containing several inversions at its 5' end, and two polyadenylation
      signals at its 3' end. The 283 nt unit is expressed in Group 1 pIg-R mRNAs; but
      it is absent in the Group 2 family so that their GAA repeats merge with their
      poly A tails. In contrast to genomic sequence, GGA triplet repeats are amplified
      (n > or = 24-26), whereas GAA triplet repeats are truncated variably (n < or = 9
      37) and expressed uninterruptedly in both mRNA Groups. These results suggest that
      3' end processing of the rat PIGR gene may involve misalignment, slippage and
      premature termination of RNA polymerase II. The function of this unusual
      processing and possible roles of chi-like octamers in quiescent or extrahepatic
      tissues are discussed.

PMID- 7739890
TI  - In vivo footprinting and functional analysis of the human c-sis/PDGF B gene
      promoter provides evidence for two binding sites for transcriptional activators.
AB  - By in vivo DMS footprint and reporter gene analyses we identified two
      transcription factor binding sites in the human c-sis/PDGF B gene promoter. The
      low basal activity of the PDGF B promoter in HeLa and undifferentiated K562
      cells, which express low PDGF B mRNA levels, and in PC3 cells, which express a
      high PDGF B mRNA level, results from binding of a weak transcriptional activator
      between positions -64 and -61 relative to the transcription start site.
      Cytotrophoblast-like JEG-3 cells, which do not express the 3.5 kb PDGF B mRNA,
      contain a transcriptional activator directed at the -64/-61 sequence, but DNA
      methylation may render the endogenous promoter inaccessible to this activator. A
      CCACCCAC element at position -61/-54 was identified as the in vivo binding site
      for a strong transcriptional activator in phorbol ester-treated megakaryocytic
      K562 cells, which express a high PDGF B mRNA level. Primary human fibroblasts,
      which do not transcribe the PDGF B gene, contain a transcriptional activator that
      recognizes an element between positions -60 and -45 but does not bind to the
      endogenous unmethylated promoter. Our results show that the complex expression
      pattern of the human PDGF B gene involves the cell type-specific expression of
      weak and strong transcriptional activators and regulation of promoter
      accessibility to these factors.

PMID- 7739891
TI  - A human protein with homology to Saccharomyces cerevisiae SNF5 interacts with the
      potential helicase hbrm.
AB  - In yeast, the SNF/SWI complex is involved in transcriptional activation of
      several inducible promoters, possibly by causing a local modification of the
      chromatin structure. Recently, two human homologues of the SNF2/SWI2 protein have
      been isolated, hbrm and BRG-1. In addition, a complex containing one of the
      SNF2/SWI2 homologues and having an in vitro activity similar to the yeast complex
      has been partially purified from HeLa cells. Here we describe the
      characterization of a cDNA encoding a human nuclear protein containing a large
      domain of homology with SNF5, another member of the yeast SNF/SWI complex. This
      protein can be co-immunoprecipitated with hbrm and the interaction between the
      two proteins is dependent on the region conserved between the human and the yeast
      SNF5. These findings suggest that the cDNA we have cloned encodes one of the
      members of the human SNF/SWI complex.

PMID- 7739892
TI  - Sequence context of antisense RelA/NF-kappa B phosphorothioates determines
      specificity.
AB  - The use of antisense oligomers to achieve inhibition of gene expression is
      complicated by frequent non-specific effects, and even the control oligomers
      often exhibit sequence-specific effects. We have recently shown that in diverse
      tumor-derived cell lines, a 24mer phosphorothioate oligomer antisense to the relA
      subunit of NF-kappa B transcription factor causes a block of cellular adhesion,
      inhibition of nuclear NF-kappa B and Sp1 DNA-binding activity and inhibition of
      tumor cell growth in vitro and in vivo. In this study we use the same model to
      attempt to define the limits of antisense specificity. We demonstrate that single
      base pair substitution can virtually abolish the antisense activity. The relative
      position of mismatches within the antisense sequence is critical to the loss of
      activity. Our results further indicate that antisense specificity is determined
      not only by the content of the sequence but also by its occurrence with reference
      to the surrounding sequences.

PMID- 7739893
TI  - Protein-peptide interactions analyzed with the yeast two-hybrid system.
AB  - The yeast two-hybrid system was used to screen a library of random peptides fused
      to a transcriptional activation domain in order to identify peptides capable of
      binding to the retinoblastoma protein (Rb). Seven peptides were identified, all
      of which contain the Leu-X-Cys-X-Glu motif found in Rb-binding proteins, although
      their activity in the yeast assay varied over a 40-fold range. Mutagenesis of the
      DNA encoding two of these peptides followed by screening in the two-hybrid system
      allowed the delineation of residues apart from the invariant Leu, Cys and Glu
      that affect binding to Rb. Binding affinities of a peptide and one of its
      variants to Rb, determined by surface plasmon resonance, correlated with results
      from the two-hybrid assay. This method offers several advantageous features
      compared to existing technology for screening peptide libraries: in vivo
      detection of protein-peptide interactions, high sensitivity, the capacity for
      rapid genetic screening to identify stronger and weaker binding peptide variants,
      and the use of a simple assay (transcriptional activity) as a means to assess
      binding affinity.

PMID- 7739894
TI  - Molecular cloning of a small DNA binding protein with specificity for a tissue
      specific negative element within the rps1 promoter.
AB  - A cDNA encoding a specific binding activity for the tissue-specific negative cis
      element S1F binding site of spinach rps1 was isolated from a spinach cDNA
      expression library. This cDNA of 0.7 kb encodes an unusual small peptide of only
      70 amino acids, with a basic domain which contains a nuclear localization signal
      and a putative DNA binding helix. This protein, named S1Fa, is highly conserved
      between dicotyledonous and monocotyledonous plants and may represent a novel
      class of DNA binding proteins. The corresponding mRNA is accumulated more in
      roots and in etiolated seedlings than in green leaves. This expression pattern is
      correlated with the tissue-specific function of the S1F binding site which
      represses the rps1 promoter preferentially in roots and in etiolated plants.

PMID- 7739895
TI  - Looped oligonucleotides form stable hybrid complexes with a single-stranded DNA.
AB  - Several new branched (1, 2), circular (9) and looped oligonucleotides (14-17)
      were synthesized. 3'-Deoxypsicothymidine was employed to create the site of
      branching when required. The circular and looped structures were obtained by
      oxidative disulfide bond formation between mercaptoalkyl tether groups. All the
      oligonucleotides prepared contained two T11 sequences, and the branched and
      looped oligomers an additional alternating CT sequence. The melting experiments
      revealed that the branched oligonucleotides form relatively weak hybrid
      (double/triple helix) complexes with the single-stranded
      oligodeoxyribonucleotide, showing a considerable destabilizing effect produced by
      the structure at the point of branching. The data obtained with looped
      oligonucleotides demonstrated considerable stabilization of the hybrid
      (double/triple helix) complexes with the complement. The data reported may be
      useful in attempting to design new antisense or antigene oligonucleotides capable
      of forming selective and stable bimolecular hybrid complexes with nucleic acids.

PMID- 7739896
TI  - Tyrosine 27 of the specificity polypeptide of EcoKI can be UV crosslinked to a
      bromodeoxyuridine-substituted DNA target sequence.
AB  - The specificity (S) subunit of the restriction enzyme EcoKI imparts specificity
      for the sequence AAC(N6)GTGC. Substitution of thymine with bromodeoxyuridine in a
      25 bp DNA duplex containing this sequence stimulated UV light-induced covalent
      crosslinking to the S subunit. Crosslinking occurred only at the residue
      complementary to the first adenine in the AAC sequence, demonstrating a close
      contact between the major groove at this sequence and the S subunit. Peptide
      sequencing of a proteolytically-digested, crosslinked complex identified tyrosine
      27 in the S subunit as the site of crosslinking. This is consistent with the role
      of the N-terminal domain of the S subunit in recognizing the AAC sequence.
      Tyrosine 27 is conserved in the S subunits of the three type I enzymes that share
      the sequence AA in the trinucleotide component of their target sequence. This
      suggests that tyrosine 27 may make a similar DNA contact in these other enzymes.

PMID- 7739897
TI  - Analysis of hepatocyte nuclear factor-3 beta protein domains required for
      transcriptional activation and nuclear targeting.
AB  - Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta and
      gamma) regulate transcription of the transthyretin (TTR) and numerous other liver
      specific genes. The HNF-3 proteins bind DNA via a homologous winged helix motif
      common to a number of developmental regulatory proteins including the Drosophila
      homeotic fork head (fkh) protein. The mammalian HNF-3/fkh family consists of at
      least thirty distinct members and is expressed in a variety of different cellular
      lineages. In addition to the winged helix motif, several HNF-3/fkh family members
      also share homology within transcriptional activation region II and III
      sequences. In the present study we further define the sequence boundaries of the
      HNF-3 beta N-terminal transcriptional activation domain to extend from amino
      acids 14 to 93 and include conserved region IV and V sequences. We also
      demonstrate that activity of the HNF-3 N-terminal domain was diminished by
      mutations which altered a putative alpha-helical structure located between amino
      acid residues 14 and 19. However, transcriptional activity was not affected by
      mutations which eliminated two conserved casein kinase I sites or increased the
      number of acidic amino acid residues in the N-terminal domain. Furthermore, we
      determined that the nuclear localization signal overlaps with the winged helix
      DNA-binding motif. These results suggest that conserved sequences within the
      winged helix motif of the HNF-3/fkh family may be involved not only in DNA
      recognition, but also in nuclear targeting.

PMID- 7739898
TI  - Comparative analysis of cleavage rates after systematic permutation of the NUX
      consensus target motif for hammerhead ribozymes.
AB  - A trans-cleaving asymmetric hammerhead ribozyme directed against an AUC decreases
      target motif within an RNA specific for human immunodeficiency virus type 1 (HIV
      1) was generated. The AUC decreases motif of the target RNA was permutated in
      order to generate all 12 variants of an NUX decreases consensus target motif,
      wherein N = A, C, G or U and X = A, C or U. Four asymmetric hammerhead ribozymes
      differing in the nucleotide that is complementary to N were generated, of which
      each was specific for three of the 12 target motifs. The residual sequence
      context within helices I and III remained unchanged. All 12 combinations resulted
      in cleavage of the target RNA. Using single-turnover conditions, the detectable
      cleavage rate constants at 37 degrees C were determined, which varied
      considerably depending on the NUX decreases motif. The NUC decreases motifs were
      cleaved more efficiently, with AUC decreases being cleaved best. Comparison with
      previous studies indicates that the sequence context of the NUX decreases motif
      plays a major role for the detectable cleavage activity.

PMID- 7739899
TI  - BspLUII III, a bifunctional restriction and modification enzyme from a
      thermophilic strain Bacillus species LUII.
AB  - BspLUII III, an isomer of FinI (1) and BsmFI (2), was found to cleave DNA at two
      points 10, 11 and 14, 15 bp in the different strands away from the recognition
      site, and in the presence of SAM it exhibits the adenine specific
      methyltransferase activity.Images

PMID- 7739900
TI  - Interaction of dimeric intercalating dyes with single-stranded DNA.
AB  - The unsymmetrical cyanine dye thiazole orange homodimer (TOTO) binds to single
      stranded DNA (ssDNA, M13mp18 ssDNA) to form a fluorescent complex that is stable
      under the standard conditions of electrophoresis. The stability of this complex
      is indistinguishable from that of the corresponding complex of TOTO with double
      stranded DNA (dsDNA). To examine if TOTO exhibits any binding preference for
      dsDNA or ssDNA, transfer of TOTO from pre-labeled complexes to excess unlabeled
      DNA was assayed by gel electrophoresis. Transfer of TOTO from M13 ssDNA to
      unlabeled dsDNA proceeds to the same extent as that from M13 dsDNA to unlabeled
      dsDNA. A substantial amount of the dye is retained by both the M13 ssDNA and M13
      dsDNA even when the competing dsDNA is present at a 600-fold weight excess; for
      both dsDNA and ssDNA, the pre-labeled complex retains approximately one TOTO per
      30 bp (dsDNA) or bases (ssDNA). Rapid transfer of dye from both dsDNA and ssDNA
      complexes is seen at Na+ concentrations > 50 mM. Interestingly, at higher Na+ or
      Mg2+ concentrations, the M13 ssDNA-TOTO complex appears to be more stable to
      intrinsic dissociation (dissociation in the absence of competing DNA) than the
      complex between TOTO and M13 dsDNA. Similar results were obtained with the
      structurally unrelated dye ethidium homodimer. The dsDNA- and ssDNA-TOTO
      complexes were further examined by absorption, fluorescence and circular
      dichroism spectroscopy. The surprising conclusion is that polycationic dyes, such
      as TOTO and EthD, capable of bis-intercalation, interact with dsDNA and ssDNA
      with very similar high affinity.

PMID- 7739901
TI  - Analysis of eukaryotic promoter sequences reveals a systematically occurring CT
      signal.
AB  - A general data study of eukaryotic promoter sequences from widely different
      species is presented. Mammalian promoters with known transcription initiation
      sites represented the largest subclass of the data, and for this group neural
      network algorithms were trained to predict the location of the initiation site in
      a test set. The prediction accuracy of this local method was higher than what
      could be expected from the known non-local structure of eukaryotic promoters.
      Subsequent analysis revealed, besides the consensus of the two known important
      subregions: the TATA-box TATAAA and the Cap-signal CA, a CT-signal positioned on
      the average seven nucleotides downstream of the transcription initiation site.
      The consensus of the CT-signal is CTNCNG. The details of this core promoter
      element were disclosed using multiple alignment and have earlier only been
      described in a few isolated examples.

PMID- 7739902
TI  - DNA bending by the a1 and alpha 2 homeodomain proteins from yeast.
AB  - Structural and biochemical studies of monomer homeodomain-DNA complexes have not
      so far revealed any cases of pronounced DNA distortion. In this paper we show
      that multimeric complexes of the yeast homeodomain proteins a1 and alpha 2
      induced significant bends in their operators upon binding. Based on a series of
      circular permutation experiments, we found that a dimer of alpha 2 bound to
      operator DNA produced a mild bend in the DNA, whereas the alpha 2-MCM1-DNA and
      the a1-alpha 2-DNA complexes exhibited much sharper bends. As these latter two
      complexes represent the in vivo form of DNA-bound a1 and alpha 2, we conclude
      that, in the cell, these homeodomain proteins are associated with pronounced
      bends in DNA. We discuss possible roles for these bends in transcriptional
      repression.

PMID- 7739903
TI  - Silkworm TFIIIA requires additional class III factors for commitment to
      transcription complex assembly on a 5S RNA gene.
AB  - We find striking similarities in promoter structure and requirements for template
      commitment on 5S RNA and tRNA genes from silkworms. The promoters are nearly the
      same size (approximately 160 bp) and include flanking as well as internal
      sequences. To analyze the factor requirements for 5S RNA transcription complex
      assembly in a completely homologous system, we have isolated a silkworm fraction
      that is highly enriched for the 5S RNA-specific transcription factor, TFIIIA.
      Using this fraction, together with the other silkworm fractions, TFIIIB, TFIIIC,
      TFIIID and RNA polymerase III, we demonstrate that the requirements for 5S RNA
      transcription complex assembly are very similar to those previously established
      for a tRNA(C)(Ala) gene. Specifically, no individual factor fraction is
      sufficient for commitment of silkworm 5S RNA genes to transcription complex
      assembly. Rather, combinations of at least three factor fractions are required.
      Our observation that more than one subset of factors is competent for commitment
      suggests that silkworm 5S RNA genes further resemble tRNA(C)(Ala) genes in their
      ability to use multiple pathways for transcription complex formation.

PMID- 7739904
TI  - Photoaffinity approaches to determining the sequence selectivities of DNA-small
      molecule interactions: actinomycin D and ethidium.
AB  - The DNA photoaffinity ligands, 7-azidoactinomycin D and 8-azidoethidium, form DNA
      adducts that cause chain cleavage upon treatment with piperidine. Chemical DNA
      sequencing techniques were used to detect covalent binding. The relative
      preferences for modifications of all possible sites defined by a base pair step
      (e.g. GC) were determined within all quartet contexts such as (IGCJ). These
      preferences are described in terms of 'effective site occupations', which express
      the ability of a ligand to covalently modify some base in the binding site.
      Ideally, the effective site occupations measured for photoaffinity agents can
      also be related to site-specific, non-covalent association constants of the
      ligand. The sites most reactive with 7-azidoactinomycin D were those preferred
      for non-covalent binding of unsubstituted actinomycin D. GC sites were most
      reactive, but next-nearest neighbors exerted significant influences on
      reactivity. GC sites in 5'-(pyrimidine)GC(purine)-3' contexts, particularly TGCA,
      were most reactive, while reactivity was strongly suppressed for GC sites with a
      5'-flanking G, or a 3'-flanking C. High reactivities were also observed for bases
      in the first (5') GG steps in TGGT, TGGG and TGGGT sequences recently shown to
      bind actinomycin D with high affinity. Pyrimidine-3',5'-purine steps and GG steps
      flanked by a T were most preferred by 8-azidoethidium, in agreement with the
      behavior of unsubstituted ethidium. The good correspondence between expected and
      observed covalent binding preferences of these two azide analogs demonstrates
      that photoaffinity labeling can identify highly preferred sites of non-covalent
      DNA binding by small molecules.

PMID- 7739906
TI  - Semi exponential cycle sequencing.

PMID- 7739905
TI  - Structural characterization of d(CAACCCGTTG) and d(CAACGGGTTG) mini-hairpin loops
      by heteronuclear NMR: the effects of purines versus pyrimidines in DNA hairpins.
AB  - The DNA decamers, d(CAACCCGTTG) and d(CAACGGGTTG) were studied in solution by
      proton and heteronuclear NMR. Under appropriate conditions of pH, temperature,
      salt concentration and DNA concentration, both decamers form hairpin
      conformations with similar stabilities [Avizonis and Kearns (1995) Biopolymers,
      35, 187-200]. Both decamers adopt mini-hairpin loops, where the first and last
      four nucleotides are involved in Watson-Crick hydrogen bonding and the central
      two nucleotides, CC or GG respectively, form the loop. Through the use of proton
      proton, proton-phosphorus and natural abundance proton-carbon NMR experiments,
      backbone torsion angles (beta, gamma and epsilon), sugar puckers and interproton
      distances were measured. The nucleotides forming the loops of these decamers were
      found to stack upon one another in an L1 type of loop conformation. Both show
      gamma tr and unusual beta torsion angles in the loop-closing nucleotide G7, as
      expected for mini-hairpin loop formation. Our results indicate that the beta and
      epsilon torsion angles of the fifth and sixth nucleotides that form the loop and
      the loop-closing nucleotide G7 are not in the standard trans conformation as
      found in B-DNA. Although the loop structures calculated from NMR-derived
      constraints are not well defined, the stacking of the bases in the two different
      hairpins is different. This difference in the base stacking of the loop may
      provide an explanation as to why the cytosine-containing hairpin is
      thermodynamically more stable than the guanine-containing hairpin.

PMID- 7739907
TI  - Sequencing of synthetic oligonucleotides and analogs by homopolymeric tailing.

PMID- 7739908
TI  - Transgenic mice for the preparation of hygromycin-resistant primary embryonic
      fibroblast feeder layers for embryonic stem cell selections.

PMID- 7739909
TI  - 6-Aza-2-thiothymine: a matrix for MALDI spectra of oligonucleotides.

PMID- 7739910
TI  - Lifetime alcohol consumption and risk of breast cancer.
AB  - The relation of lifetime alcohol intake to risk of breast cancer in pre- and
      postmenopausal women was examined in a case-control study in western New York.
      Cases with incident primary histologically confirmed breast cancer diagnosed
      during the period 1986-1991 (n = 740) and controls, frequency age-matched women
      drawn from New York state driver's license records (age < 65 yrs) and from
      records of the Health Care Finance Administration (age > or = 65 yrs, n = 810),
      were interviewed regarding intake of wine, beer, and hard liquor 2, 10, and 20
      years ago and at 16 years of age. Although women in this study had generally low
      intakes of alcohol, there was little evidence of increased risk of breast cancer
      with intake of alcohol at any of the time periods or with an index of total
      lifetime intake. There was a weak indication of an increase in risk with beer for
      intakes of at least one drink per day. This risk was evident for 2, 10, and 20
      years ago but not at 16 years of age. In this group with relatively low intakes
      of alcohol, evidence was weak for an association of increased risk of breast
      cancer with intake of alcohol, with the possible exception of a weak association
      with beer intake.

PMID- 7739911
TI  - Effects of dietary restriction and fasting on selected rat liver enzymes of
      xenobiotic metabolism and on AOM-induced DNA guanine methylation in rat liver and
      colon.
AB  - Using five- to eight-week-old male F344 rats and a high-fat (23.5% corn oil)
      modified AIN-76A diet, we examined the effects of dietary restriction (a 3-wk 30%
      reduction of food intake with respect to ad libitum-fed controls) or complete
      fasting (2 days without food) on the activities of hepatic xenobiotic
      metabolizing enzymes in vitro and on azoxymethane- (AOM) induced formation of O6
      methylguanine and 7-methylguanine in liver and colon DNA in vivo. Compared with
      ad libitum-fed rats, fasting increased total liver cytochrome P450 by 32%,
      microsomal aniline hydroxylase by 270%, N-nitrosodimethylamine demethylase by
      270%, and azoxymethane hydroxylase by 320%. Liver benzo[a]pyrene (BP) hydroxylase
      and glutathione-S-transferase were decreased by 39% and 21%, respectively,
      whereas NADPH cytochrome c reductase and UDP glucuronyltransferase were
      unchanged. DNA methylation in the livers of fasted animals was 20-31% greater six
      hours after a 15 mg/kg sc injection of AOM than in ad libitum-fed controls,
      whereas DNA methylation in the colon was slightly lower. In three-week diet
      restricted animals. there were small but not statistically significant changes in
      the various enzyme activities and in AOM-induced DNA methylation compared with
      the ad libitum-fed controls, with the exception of BP hydroxylase, which showed a
      26% decrease. However, the trends in the increase or decrease of each parameter,
      although small in magnitude, were similar to those observed in the case of
      fasting, suggesting that the effects might become significant if the duration of
      diet restriction were prolonged. The enhancement of AOM metabolism in rat liver
      by fasting, leading to increased liver DNA methylation, is different from that
      produced by chemical inducers, such as ethanol, where no increase in liver DNA
      methylation is observed.

PMID- 7739912
TI  - Differential effects of tumor and parenteral nutrition on jejunal mucosal
      polyamines.
AB  - Nutritional repletion of tumor-bearing (TB) organisms by means of total
      parenteral nutrition (TPN) has been associated with gut atrophy,
      immunosuppression, and increased infection rate. To assess possible molecular
      mechanisms of intestinal atrophy during TPN, jejunal mucosal polyamine
      concentrations and biosynthetic activity were assessed in non-TB (NTB) and TB
      rats maintained on rat chow or TPN for eight days. As expected, jejunal mucosal
      protein content was decreased in both groups of rats maintained on TPN. Although
      mucosal concentration of putrescine was decreased in TB groups and in the NTB
      group maintained on TPN, levels of spermidine and spermine were decreased only in
      the NTB-TPN group. Spermidine levels were elevated significantly in both TB
      groups. The concentration of spermine was also elevated in the TB-TPN group but
      was not changed in the TB group maintained on chow. Activity of ornithine
      decarboxylase was increased in the NTB-TPN group but was not altered
      significantly in either TB group. S-adenosylmethionine decarboxylase activity was
      decreased significantly in TB rats maintained on chow and was increased back to
      control level in the TB-TPN group. These results suggest that jejunal mucosal
      polyamines are decreased in NTB rats maintained on TPN. Additionally, it appears
      that enzyme activity is induced in NTB-TPN rats, perhaps in response to the
      reduction in polyamines and gut atrophy. The absence of similar changes in TB
      rats maintained on TPN suggests that regulatory mechanisms of polyamine
      biosynthesis, such as product inhibition, may be refractory. In addition,
      polyamine biosynthesis from other sources, such as tumor tissue, may be affecting
      the control of intestinal polyamine biosynthesis.

PMID- 7739913
TI  - Differences in intake of specific food plants by Polynesians may explain their
      lower incidence of colorectal cancer compared with Europeans in New Zealand.
AB  - Epidemiological studies have implicated obesity; high intakes of alcohol, fat,
      and energy; and low intakes of food plants as risk factors for colorectal cancer.
      In New Zealand, Polynesians (including Maoris and people from several Pacific
      Islands) are more likely to be overweight and have higher intakes of fat and
      energy than Europeans, and they are likely to have similar total intakes of food
      plants. Yet, in New Zealand, Polynesians have a significantly lower incidence of
      colorectal cancer than the Europeans. It is possible that the difference in
      incidence of colorectal cancer is due to differences in consumption of specific
      food plants by Polynesians and Europeans in New Zealand. Here we have compared
      the consumption of specific food plants by 429 Maoris, 643 Pacific Islanders, and
      4,451 Europeans in paid employment in New Zealand. Of the 51 food plants eaten by
      New Zealanders, 6 were eaten significantly more frequently and 17 significantly
      less frequently by the two Polynesian groups than by Europeans. The quantity of
      any protective chemical components (or other as yet unknown protective factors)
      in food plants is likely to be related to their botanical classification.
      Differences in the intake of specific food plants may at least partly explain
      differences in the incidence of colorectal cancer between Polynesians and
      Europeans.

PMID- 7739914
TI  - Vitamin E succinate induction of HL-60 cell adhesion: a role for fibronectin and
      a 72-kDa fibronectin-binding molecule.
AB  - HL-60 cells, growing as single cells in suspension, exhibit marked cell-cell
      adhesion when treated for 24 hours with 10 micrograms/ml RRR-alpha-tocopheryl
      succinate, also called vitamin E succinate (VES). VES-induced cell-cell adhesion
      is dependent on divalent cations and a functional cytoskeleton and is protein
      mediated. Cell adhesion molecules CD11a/CD18, CD11b/CD18, CD29, and CD54 do not
      appear to be mediating VES-induced cell adhesion. HL-60 cells treated with VES
      adhere to fibronectin-coated plastic and secrete elevated levels of fibronectin.
      A 72-kDa fibronectin-binding membrane molecule was detected on VES-treated HL-60
      cells, and antibodies to fibronectin were shown to inhibit VES-induced cell
      aggregation. VES induction of HL-60 cell-cell adhesion is proposed to result from
      increased amounts of extracellular fibronectin binding to VES-induced cell
      surface fibronectin-binding molecules.

PMID- 7739915
TI  - Alcohol and endometrial cancer risk: findings from an Italian case-control study.
AB  - Using data from a case-control study conducted in Northern Italy, we analyzed the
      relation between alcohol drinking and risk of endometrial cancer. Cases were 726
      patients, < 75 years of age, admitted to the Ospedale Maggiore (including the 4
      largest teaching and general hospitals in the Greater Milan area), the University
      Obstetrics and Gynecology Clinics, and the National Cancer Institute of Milan
      with histologically confirmed endometrial cancer. Controls were 2,123
      nonhysterectomized patients, < 75 years of age, admitted for acute
      nongynecological non-hormone-related nonneoplastic conditions to the same network
      of hospitals where cases had been identified. When total consumption of all
      alcoholic beverages was considered, 68.2% of cases and 63.9% of controls were
      drinkers and 12% of cases and 9.3% of controls reported > or = 2 drinks/day.
      Considering total alcohol drinking, the relative risk for alcohol drinkers vs.
      nondrinkers was 1.3 (95% confidence interval 1.1-1.5), and the RR estimates for
      subsequent levels of intake were 1.1, 1.4, and 1.6 for women drinking > 0 < or =
      1, > 1 < or = 2 drinks/day (chi 2(1) trend 11.33, p < 0.001). The estimates were
      similar when wine only (which represents the large majority of all alcohol intake
      in Italy) was considered, whereas data were less informative for beer and spirits
      intake only. No relation emerged between duration of alcohol consumption and risk
      of endometrial cancer. These findings suggest a potential link between alcohol
      drinking and endometrial cancer risk and are, in any case, inconsistent with a
      protective role of alcohol in endometrial carcinogenesis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7739916
TI  - Beef tallow, but not corn bran or soybean polysaccharide, reduces large
      intestinal and fecal bile acid concentrations in rats.
AB  - Diets high in fat and low in dietary fiber have been associated with a higher
      incidence of colon cancer, possibly by increasing bile acid concentration in the
      colon. Therefore changes in bile acid metabolism due to beef tallow, corn bran
      (CB), and soy polysaccharide (SP) feeding were studied. Rats were fed one of four
      diets for six weeks: 5% beef tallow fiber-free (LF), 20% beef tallow fiber-free
      (HF), 20% beef tallow with CB (HFCB), and 20% beef tallow with SP (HFSP). HF
      increased fecal output compared with LF, and HFCB and HFSP increased fecal output
      compared with HF. HF reduced fecal bile acid concentration by two-thirds compared
      with LF, although daily bile acid excretion was similar. There was a tendency
      toward a smaller bile acid quantity in the small intestine with HF than with LF.
      Neither fiber altered total fecal bile acid concentration or small intestinal
      bile acid quantity compared with HF. However, 7 alpha-dehydroxylase activity in
      the colon was lower with HFSP than with HFCB. Increasing dietary beef tallow from
      5% to 20% in animals fed a fiber-free diet greatly reduced the concentration of
      bile acids in the large intestine and feces, an effect associated with a reduced
      risk of colon cancer.

PMID- 7739917
TI  - Cruciferous vegetables and glutathione: their effects on colon mucosal
      glutathione level and colon tumor development in rats induced by DMH.
AB  - The effect of a diet containing 10-40% lyophilized cabbage or broccoli as
      cruciferous vegetable or 10-40% lyophilized potato as noncruciferous vegetable
      fed for 14 days on the colon mucosal glutathione (GSH) level was studied in male
      rats. The GSH levels of the duodenum mucosa and the liver were also measured.
      Cabbage and broccoli enhanced the colon and duodenum mucosal GSH levels in a dose
      related manner; potato had no effect. All three vegetables had no effect on the
      liver GSH level. The effect of GSH on colon tumorigenesis induced by 1,2
      dimethylhydrazine (DMH) was also examined in rats. Male Sprague-Dawley rats were
      injected with DMH (20 mg/kg body wt) weekly for 20 weeks. DMH lowered the colon
      mucosal GSH level. GSH (100 mg/day/rat) dissolved in the drinking water and given
      to rats during and after DMH injections had little or no effect on tumor
      incidence and total number of colon tumors. Tumors were larger in rats that
      received GSH than in those that received water. This study shows that the colon
      mucosal GSH level can be enhanced by feeding rats a diet high in cabbage or
      broccoli and that GSH added to the drinking water did not affect DMH-induced
      colon tumorigenesis under the experimental conditions used.

PMID- 7739918
TI  - Levels of amino acids in human hepatocellular carcinoma and adjacent liver
      tissue.
AB  - Total parenteral nutrition can be used to overcome amino acid imbalance in cancer
      patients. Because there is little documentation of treatment for amino acid
      imbalance in patients with hepatocellular carcinoma (HCC), we designed a study 1)
      to compare tissue levels of amino acids between HCC and the adjacent liver and 2)
      to determine which serum amino acids correlate to tumor volume. A significant
      elevation of methionine and a significant decrease of glycine and cystine were
      observed in HCC compared with adjacent liver tissue, and a significant
      correlation was found between tumor volume and serum methionine levels (r = 
      0.636, p < 0.01). Thus the tumor tissue competes successfully with host tissue
      for nitrogen substrates, particularly methionine, and an accelerated protein
      synthesis in HCC consumes large amounts of these amino acids. The possibility of
      methionine-depleted treatment could be considered for patients with HCC.

PMID- 7739919
TI  - Chemopreventive action of oriental food-seasoning spices mixture Garam masala on
      DMBA-induced transplacental and translactational carcinogenesis in mice.
AB  - The present study deals with the chemopreventive action of the food-seasoning
      spices mixture Garam masala on dimethylbenz[a]anthracene (DMBA)-induced
      translactational and transplacental carcinogenesis in mice. When pregnant mice
      were given 10 and 30 mg of Garam masala per day from Days 13-19 of gestation in
      addition to DMBA (5 mg/day) on Days 15-17 of gestation, the multiple-site tumor
      incidence declined significantly from control level of 62% to 19% and 10%,
      respectively, in F1 progeny. Furthermore the mean numbers of tumors per effective
      F1 mouse were reduced from the control value of 1.27 to 0.64 at the lower dose
      level (10 mg) and 0.23 at the higher dose level (30 mg) of Garam masala.
      Likewise, when lactating mice were given Garam masala at 10 and 30 mg/day for the
      first 15 days of lactation in addition to DMBA (3 mg/day) on Days 3, 6, 9, 12,
      and 15 of lactation, the multiple-site tumor incidence was reduced significantly
      from control level of 66% to 23% and 14%, respectively, in F1 progeny. The mean
      numbers of tumors per effective F1 mouse declined from control value of 1.43 to
      0.46 at the lower dose and 0.25 at the higher dose of Garam masala. Further
      studies are required to analyze the nature of active chemical components and the
      manner in which they achieve chemoprevention in these complex model systems.

PMID- 7739920
TI  - [Diagnostic and therapeutic approach in uropathic abnormalities diagnosed in
      utero].
AB  - Ultrasonography permits to suspect urinary tract abnormalities in fetal age:
      hydronephrosis is one of the most frequent anomalies detected, but renal
      dysplasia (multicystic kidney, renal agenesis, renal cysts) can be found in some
      cases. At birth, if abnormalities are confirmed by ultrasound scan other
      instrumental investigation are needed: cystography, to exclude vesicoureteric
      reflux, and sequential scintigraphy, to evaluate if obstruction of urinary tract
      is present or to confirm the suspect of renal agenesis or multicystic dysplasia.
      Urography could be necessary in some cases. For bilateral uropathy evaluation of
      renal function with blood tests is required. Early surgery is needed in case of
      severe obstructive uropathy; if obstruction is mild the patients can be followed
      with instrumental investigation. Antibiotic prophylaxis is required to prevent
      urinary tract infections in patients with vesicoureteric reflux. The indications
      for surgery in patients with vesico-ureteric reflux are still unclear.

PMID- 7739921
TI  - [Indications for recombinant growth hormone (rhGH) treatment in kidney diseases].
AB  - Growth retardation is one of the major problem in children with chronic and
      terminal renal failure. The growth hormone-insulin-like growth factor axis is
      altered in uraemia, resulting in peripheral resistance. This insensitivity seems
      to be overcome in an experimental study by supraphysiological doses of
      recombinant human growth hormone (rhGH). Several clinical studies have confirmed
      that rhGH increases growth velocity in children with chronic renal failure with
      and without dialysis and after renal transplant, without significant side
      effects. The improvement of growth is more marked in prepubertal patients and
      during the first year of rhGH treatment. Also in our experience prepubertal
      children showed an increase of height standard deviation score and growth
      velocity during rhGH treatment; the pubertal patients failed to improve their
      statural growth. GH, as the prototype of an anabolic hormone, has also great
      potential in improving catabolic conditions of various origin, particularly those
      due to renal failure. RhGH can improve nitrogen balance and the nutritional
      parameters with an increase of muscle mass and a decrease of fat mass.
      Prospectively, rhGH could be utilized to improve the hypercatabolic condition of
      acute renal failure. The following analysis will discuss the recent studies
      employing rhGH in renal diseases and will attempt to give some guide lines to
      rhGH treatment in these illnesses.

PMID- 7739922
TI  - [Cryptorchidism].
AB  - Cryptorchidism is the most frequent anomaly of an endocrine gland; it entails
      risks of infertility and testicular cancer. Its pathogenesis is thought to be
      multifactorial including anatomical and mechanical together with endocrine
      causes. In the last decades most Authors favoured the hypothesis that some degree
      of androgen insufficiency during fetal life may play a role in determining
      testicular maldescent. Morphological alterations have been demonstrated in
      cryptorchidism testes since birth; both tubular and interstitial damage already
      can be found in the first months of life. A critical phase in germinal
      development occurs during the third month when gonadotropin and testosterone
      postnatal surge induces the first maturational step in germ cells development. In
      cryptorchid infants, gonadotropin insufficiency at this time reduces germ cells
      differentiation, leading to progressive germinal decline, which becomes manifest
      after 12 months of life. In the opinion of some Authors, germinal alteration can
      be partially reversed by early scrotal reposition of the cryptorchid testes.
      Hormonal therapy with human chorionic gonadotropin (HCG) and luteinizing hormone
      releasing hormone (LHRH) has been used in the past decades with variable results.
      A combination of the two hormones has had a greater effect in inducing testicular
      descent compared to single hormone treatment. Although some surgeons already
      treat cryptorchid patients during childhood, an increasing number of pediatric
      surgeons believe that early treatment, performed during infancy is preferable,
      when considering the early and progressive histological damage seen in
      cryptorchid gonads. In our opinion, also hormonal treatment performed during the
      first year of life seems preferable since it can at the same time induce scrotal
      descent of cryptorchid testes and substitute postnatal gonadotropin
      insufficiency.

PMID- 7739923
TI  - [Status asthmaticus].
AB  - Through a careful examination of the up-to-date literature on the subject, the
      Authors provide a full account of the present knowledge about the physiopathology
      of the status asthmaticus; at the same time they draw a practical exhaustive
      guide to the treatment to be carried out in hospital. The work arises from the
      considerable increase of mortality rate, due to asthma, recorded in the last few
      years.

PMID- 7739924
TI  - [Role of extracorporeal circulation in reversible acute cardiorespiratory
      insufficiency in neonatal and pediatric intensive care].
AB  - In the present study we try to analyze indications, contra-indication, side
      effects and limits of the use of extracorporeal circulation in neonatal and
      pediatric patients affected by reversible acute cardiorespiratory failure. The
      greatest experience on this technique has been achieved in the neonatal age
      (about 6000 newborns have been treated until now), while the employment in the
      pediatric age appears more recent (about 500 patients). Moreover, we focused on
      the drop-in criteria for neonatal and pediatric patients and on the clinical
      aspects and laboratory findings which can anticipate the surviving rate; the
      latter appears in any case much greater in the neonatal patient compared to the
      other pediatric ages.

PMID- 7739925
TI  - [Rheumatic fever: a retrospective study of a case series of the last 20 years].
AB  - The incidence of rheumatic fever in the last twenty years in our ward is
      reviewed. A substantial decrease is noted; anyway a peak in the years '80-'86 is
      reported, accordingly literature. Carditis is a frequent manifestation, but its
      clinical impact is less severe than in the past. Arthritis may have an unusual
      feature. A good compliance to prophylaxis has been obtained by a strict follow
      up.

PMID- 7739926
TI  - [Effects of recombinant human erythropoietin in the treatment of anemia of
      prematurity].
AB  - 13 premature babies (gestational age 31.1 +/- 0.9 weeks and birth weight 1586 +/-
      261 g) were randomly assigned to receive recombinant human erythropoietin (200
      U/kg i.v. three times a week during 4 weeks) or no (13 babies) as soon as
      haematocrit decrease < 30% between second and seventh week (TO). The two groups
      had similar gestational age, birth weight, Apgar score 1' and 5', O2-therapy,
      IPPV and volume of packed erythrocytes transfused before TO. Treatment was
      started at 30 +/- 0.5 days (range 21-42). At TO all subjects had not
      cardiopulmonary compromission, sepsis, O2-dependence, GMH-IVH > or = 2 degree
      grade and received iron and Vit. E by i.m. Result were evaluated through
      determination of hemoglobin, haematocrit, reticulocytes and volume of packed
      erythrocytes before and on days 7, 14, 21 and 28 of therapy. After rHuEPO the
      number of reticulocytes increased on days 21 and 28 of therapy (on day 21: 92.4
      +/- 34.2 x 1000/L vs. 71.8 +/- 21.0, p < 0.10; on day 28: 116.2 +/- 42.9 vs. 83.8
      +/- 23.2, p < 0.05); otherwise the number of transfusion (0.2 +/- 0.4 vs. 1.0 +/-
      1.2, p < 0.10) and volume of packed erythrocytes (3.0 +/- 6.3 ml/kg vs. 14.9 +/-
      15.9, p < 0.05) were reduced. Serum erythropoietin levels did not change during
      treatment, probably because, reducing the lowering of hemoglobin, hypoxic
      stimulus to increase of erythropoietin was suppressed.

PMID- 7739927
TI  - [Evaluation of the compliance of thalassemic patients at a structured ambulatory
      day hospital].
AB  - The institution of a self-constructed Ambulatory where both pediatric and adult
      patient can be assisted with Day-Hospital, gains novelty and new characteristics
      when four different physicians (Medical, Pediatrician, Hematologist and
      Psychologist) structured part-time, contribute to functionality with equal
      participation. Compliance was investigated through a computerized way.

PMID- 7739928
TI  - [Use of quinolones in the treatment of Pseudomonas aeruginosa infections in
      children with cystic fibrosis].
AB  - Quinolones, elective drugs for Pseudomonas aeruginosa (P. aeruginosa) pulmonary
      infections in Cystic Fibrosis (C.F.) patients, are controversially administered
      in prepuberal age for their arthropathic toxicity. We report the result of
      retrospective study on the use of quinolones in a group of 43 CF patients. The
      patients were divided into two groups: below 18 years (22 pts.) and over 18 (21
      pts.). All patients were evaluated clinically with the scoring system Shwachman
      and Kulczyk. Ciprofloxacin and Ofloxacin (15/20 mg/kg/die) were administered. In
      11.6% of the patients, all belonging to the second group, side effects, such as
      urticaria, tongue oedema, foreskin erythema, generalised erythema and itch, were
      described. No side effect has been reported in the patients below 18 years. Two
      patients complained knee arthralgias not related to the quinolones
      administration: in fact in the first case the demineralisation seemed to be
      responsible of the arthralgia, while in the second case an immunological disorder
      (ANA+, ICC+) should be involved in the pathogenesis of arthritis. Height velocity
      evaluation showed the same slowering of the CF untreated patients. In conclusion,
      our study confirms that quinolones use in indicated in severe and infective
      complications of CF on the basis of their efficacy, safety and their slight
      adverse effects similar to those of other potent antibiotic. Moreover our results
      confirm that no quinolone-induced cartilage toxicity is present in CF patients.

PMID- 7739929
TI  - [Clinical heterogeneity at the diagnosis in a cystic fibrosis population].
AB  - We report a study of 128 patients, affected by cystic fibrosis, followed by
      Ospedale Bambino Gesu Center for diagnosis and therapy of cystic fibrosis. We
      evaluated, in a retrospective study, the principal symptoms at diagnosis of
      cystic fibrosis, underlining the frequent finding of not classically related
      symptoms. Median age at diagnosis was of 29 months, similar to that of other
      national centers. Furthermore, we report the percentages of diagnostic mistakes,
      which preceded cystic fibrosis diagnosis (22% of total). Considering the
      incidence of the disease in Italy (1:3000 live births), a careful valuation of
      related symptoms is necessary, even if gastrointestinal and/or respiratory
      disturbances are mild or underestimated, in order to reduce median age at
      diagnosis, still too high in Italy, compared to that reported by many North
      European countries.

PMID- 7739930
TI  - [Ultrasonographic aspects of Sinding-Larsen-Johansson disease].
AB  - Sinding-Larsen-Johansson disease affects the patellar tendon in its attachment to
      the patella. It is quite frequent in adolescents, especially in young males
      practising sporting activities. The diagnosis is mainly clinical. The presence of
      tenderness and localized swelling of the lower pole of the patella are
      characteristic of the disorder. We analyzed three patients with Sinding-Larsen
      Johansson disease. Ultrasound gave complete informations about the involvement of
      bone, cartilage and patellar tendon. In these patients the lower pole of the
      patella appeared irregular, fragmented, with swelling of the cartilage and
      thickening at the insertion of the patellar tendon. Ultrasonography is also
      suitable for periodical follow-up the course of the disease.

PMID- 7739931
TI  - [Medullary sponge kidney with severe renal function impairment: a case report].
AB  - The term medullary sponge kidney refers as a renal parenchymal malformation
      characterized by cystic dilatation of the collecting ducts. Although medullary
      sponge kidney is a congenital disease, it is rarely identified in childhood and
      is usually discovered in adulthood. We report a child with bilateral medullary
      sponge kidney who, in addition to typical urographic findings, presented an
      unfavorable evolution that ended in renal chronic insufficiency. This outlook is
      uncommon and is described in only 10% of affected subjects.

PMID- 7739933
TI  - [Pena-Shokeir syndrome: report of a case with benign outcome].
AB  - Pena-Shokeir syndrome is a rare, often lethal disease, characterized by
      intrauterine growth retardation and by fetal akinesia or hypokinesia that leads
      to craniofacial anomalies, limb ankylosis, polyhydramnios and pulmonary
      hypoplasia. The case that we report had a favourable evolution, although there
      was at birth a severe respiratory distress. EMG studies revealed deficit of
      innervation. Contraceptive therapy, wrongly used by the mother in the first
      period of pregnancy, played, probably, a concomitant role in the pathogenesis of
      the syndrome.

PMID- 7739932
TI  - [Dyslipidemia and reduced fibrinolysis in a child with hemolytic-uremic
      syndrome].
AB  - Many pathogenetic factors may enhance coagulation process and induce thrombosis.
      The Authors report a case of hemolytic-uremic syndrome, with marked evidence of
      macroscopic kidney thrombotic involvement, in which an important dyslipidemia
      (hypertriglyceridemia and hypercholesterolemia) was detected during the phase of
      clinical improvement. These findings, and the contemporary marked reduction of
      fibrinolytic activity, seem to be relevant pathogenetic factors in this case. The
      treatment with polyunsaturated fatty acids Omega 3 may have been helpful in
      modifying these serum abnormalities and maybe could have brought to the clinical
      improvement.

PMID- 7739934
TI  - [Multiple hepatic abscesses: a pediatric case report].
AB  - The Authors describe the case of an immunologically healthy 14 year old boy
      presenting a hepatic infection with multiple abscesses. This case is of
      particular interest because of its rarity in Pediatrics. Probable etiologies,
      pathogenic mechanisms and treatments are discussed. The Authors underline the
      usefulness of ultrasonography as a diagnostic tool and as a non-invasive means of
      following the course of the disease.

PMID- 7739935
TI  - [Glioblastoma multiforme: a high-malignancy astrocytoma. Report of a clinical
      case with sudden onset].
AB  - We report the case of a child, 11 years old, admitted to our hospital for
      headache persisting for a week, without any other symptoms. CT scanner was
      performed, showing an infiltrating lesion of right parietal-temporal lobe. MRI
      confirmed the diagnosis. The histological examination showed a glioblastoma
      multiforme. This brain tumor is rare during pediatric age and presents a poor
      prognosis. The case reported emphasises the importance to give attention to an
      sudden and persistent headache in children without other symptoms and in a good
      state of health.

PMID- 7739936
TI  - [Trisomy 18 with unusual clinical and chromosome features].
AB  - The Authors describe a newborn with costal hypoplasia and vertebral malformation,
      tracheoesophageal fistula, congenital heart disease and closed hands with the
      second and third finger overlapping. Cytogenetic findings indicated trisomy 18
      [47, XX, -1, +der(1), +der(18), t(1;18) (q1.2; p11.3)] inherited by mother's
      carried balanced translocation 1q/18.

PMID- 7739937
TI  - [Congenital pseudoarthrosis of the clavicle. A case report].
AB  - A case of congenital pseudo-arthrosis of clavicle is reported and the peculiar
      clinical-radiological aspects, useful in the differential diagnostic with the
      much more common traumatic fracture caused by childbirth and the cleidocranial
      dysostosis are discussed.

PMID- 7739938
TI  - [Treatment of corticoid-resistant nephrotic syndrome: a still unresolved
      problem].
AB  - The nephrotic syndrome persists unchanged after the initial course of steroid
      therapy in 15 to 20% of patients. In such cases, the severity of the condition
      lies essentially in the risk of developing end-stage renal failure. This occurs
      in one third to one half of the cases. Furthermore, some of these children are at
      risk for recurrence of their original disease in the transplanted kidney. The
      course of steroid resistant nephrotic syndrome (SRNS) is usually punctuated by
      the need for numerous hospitalizations for mobilization of edema and treatment of
      infection. The treatment of patients with SRNS presents a major problem in the
      field of pediatric nephrology. Immunosuppressive agents may be efficient in some
      of steroid-resistant patients, inducing remission of proteinuria and protecting
      renal function. Unfortunately, all these agents have a low therapeutic index.
      Thus, in deciding whether, how, and when to use immunomodulating drugs, the
      nephrologist should be aware of their potential side effects, of the results that
      may be obtained and of the possible strategies for maximizing their therapeutic
      index.

PMID- 7739939
TI  - [Nager's syndrome].

PMID- 7739940
TI  - High-performance capillary electrophoresis in the pharmaceutical sciences.
AB  - High-performance capillary electrophoresis (HPCE) is a new separation technique
      that is applied in the pharmaceutical sciences. Separations by HPCE occur in a
      narrow-bore capillary under the influence of an applied electrical field.
      Components of the sample matrix are separated and migrate at different rates
      based on physicochemical properties, including ionic charge, charge to mass
      ratio, lipid solubility, and spatial orientation. Detection is achieved through
      an on-line capillary detection window. The technique has several advantages, such
      as rapid analysis times, automation, and minute sample volume requirements.
      However, a significant disadvantage of HPCE is the high concentration limit of
      detection. Although HPCE will not displace traditional separation techniques, it
      will add another dimension to existing laboratories.

PMID- 7739941
TI  - Drug-associated asymptomatic elevations of transaminase in drug safety
      assessments.

PMID- 7739942
TI  - Therapeutic equivalence of a generic slow-release theophylline tablet.
AB  - STUDY OBJECTIVE: To evaluate the relative bioavailability and clinical efficacy
      of two slow-release theophylline products. DESIGN: Randomized, double-blind,
      crossover trial. SETTING: A university-affiliated clinical research center.
      PATIENTS: Fourteen adults with asthma. INTERVENTIONS: The patients received a
      generic slow-release theophylline tablet or Theo-Dur at bedtime for 5 nights.
      MEASUREMENTS AND MAIN RESULTS: Serum drug concentrations were measured after the
      last dose. Attenuation of exercise-induced bronchospasm (EIB) was included as a
      surrogate for efficacy. There was no significant difference in extent of
      absorption. The mean differences between the generic product and Theo-Dur in area
      under the curve was -13.9 micrograms/ml.hr-1 (95% CI -41 to 12.9, p = 0.3) and in
      peak concentration (Cmax), -0.5 microgram/ml (95% CI -1.7 to 2.7, p = 0.6). In
      contrast, the generic product was absorbed more rapidly; the mean differences in
      the time to peak concentration (Tmax) was -3.0 hours (95% CI -4.3 to -1.7, p =
      0.0003), in trough concentration (Cmin), -0.9 microgram/ml (95% CI -1.9 to -0.01,
      p = 0.05), and in fluctuation between Cmax and Cmin, +128% (95% CI 40 to 217, p =
      0.008). Neither product effectively attenuated EIB, since mean serum
      concentrations during the exercise challenges were unexpectedly below 10
      micrograms/ml after both products. CONCLUSION: These two products are not
      bioequivalent, but the difference in absorption rates is unlikely to be
      clinically important in most patients (i.e., they are therapeutic equivalents).

PMID- 7739943
TI  - The effect of isoflurane versus balanced anesthesia on rocuronium's
      pharmacokinetics and infusion requirement.
AB  - STUDY OBJECTIVE: To compare the effects of two anesthetic techniques, balanced
      and isoflurane anesthesia, on the response to an intubating dose and an infusion
      of rocuronium, and on rocuronium's pharmacokinetics. DESIGN: Randomized, open
      label study. SETTING: A university-affiliated hospital. PATIENTS: Twenty-two
      healthy adults undergoing elective surgery. INTERVENTIONS: The patients were
      anesthetized with a balanced technique (nitrous oxide, fentanyl, midazolam) or
      isoflurane (nitrous oxide, isoflurane 0.5-1.0%). Rocuronium was administered
      initially as a 500-micrograms/kg bolus, then by infusion to maintain
      approximately 86-94% depression of twitch tension. Plasma samples to determine
      rocuronium concentrations were obtained before, during, and after the infusion.
      Pharmacokinetics were determined using a population-based approach. MEASUREMENTS
      AND MAIN RESULTS: Onset time and initial recovery after the bolus dose were
      similar for the two groups. Infusion requirements also were similar. Plasma
      clearance was greater during isoflurane than during balanced anesthesia (4.48 vs
      3.49 ml/kg/min). Distribution clearances and volumes of distribution were similar
      for the two groups. CONCLUSIONS: The similarity of response to an intubating dose
      and an infusion of rocuronium suggests that clinicians need not alter the dose or
      rate of rocuronium administration during isoflurane anesthesia with a of duration
      less than 1 hour. However, the greater clearance of rocuronium, in light of the
      similarity of infusion requirements, suggests that isoflurane potentiates
      rocuronium compared with balanced anesthesia.

PMID- 7739944
TI  - Hemodynamic effects of intravenous famotidine in patients undergoing cardiac
      surgery.
AB  - STUDY OBJECTIVE: To determine the hemodynamic effects of famotidine in patients
      undergoing cardiac surgery. DESIGN: A prospective, randomized, double-blinded,
      placebo-controlled study. SETTING: A large university teaching hospital.
      PATIENTS: Twenty-one patients undergoing elective cardiac surgery with
      cardiopulmonary bypass. INTERVENTIONS: The patients received a rapid intravenous
      bolus injection of famotidine 20 mg or saline placebo after anesthesia induction.
      A second dose was given 12 hours after surgery in the intensive care unit.
      MEASUREMENTS AND MAIN RESULTS: Serial hemodynamic measurements (heart rate,
      arterial blood pressure, cardiac index, pulmonary arterial pressure, central
      venous pressure, systemic vascular resistance) were obtained after each
      famotidine or placebo dose and analyzed by ANOVA: The values were not altered (p
      > 0.05) after intraoperative or postoperative famotidine or placebo
      administration. CONCLUSIONS: Rapid intravenous bolus administration of famotidine
      does not alter patient hemodynamics after anesthesia induction or in the
      intensive care unit after cardiac surgery.

PMID- 7739945
TI  - Hemodynamic effects of intravenous famotidine in critically ill patients.
AB  - STUDY OBJECTIVE: To study the hemodynamic effects of famotidine administered
      undiluted intravenously over 2 minutes. DESIGN: Nonblinded, nonrandomized.
      SETTING: Medical/surgical intensive care unit in a university-affiliated,
      tertiary care, teaching hospital. PATIENTS: Eleven consecutive critically ill
      patients receiving famotidine for stress ulcer prophylaxis. Seven of these
      patients were also receiving vasopressors or inotropes. INTERVENTIONS: Famotidine
      20 mg/2 ml was administered intravenously undiluted through a peripheral line
      over 2 minutes. All other medications, including vasopressors and inotropes, were
      held constant. MEASUREMENTS AND MAIN RESULTS: No clinically important (> 20
      variations from baseline) or statistically significant (p < 0.05) changes were
      seen in heart rate, mean pulmonary arterial pressure, cardiac output,
      systolic/diastolic blood pressure, systemic vascular resistance, or central
      venous pressure. Mean arterial pressure (MAP) was elevated at 8 minutes following
      famotidine (91.2 mm Hg [22.4 SD]) versus baseline (86.7 mm Hg [19.6 SD]).
      Pulmonary capillary wedge pressure (PCWP) was elevated at 8 minutes (17.2 mm Hg
      [6 SD]), 12 minutes (17.9 mm Hg [5.68 SD]), and 16 minutes (17.8 mm Hg [6.08
      SD]), versus baseline (14.8 mm Hg [7.14 SD]). These changes in MAP and PCWP
      achieved statistical significance, but were not thought to be of clinical
      significance. CONCLUSIONS: Famotidine given undiluted intravenously over 2
      minutes produced no adverse hemodynamic effects in critically ill patients.
      Administration in this manner should be safe even in patients requiring
      supportive cardiovascular drug therapy.

PMID- 7739946
TI  - Pharmacokinetics of fluconazole in immune-compromised children with leukemia or
      other hematologic diseases.
AB  - STUDY OBJECTIVE: To describe the pharmacokinetics of fluconazole in immune
      compromised children with leukemia or other hematologic disease. DESIGN:
      Prospective. SETTING: Children's Health Care-Minneapolis hematology/oncology
      inpatient ward and outpatient clinic. PATIENTS: Ten immune-compromised children
      (mean +/- SD age 7.4 +/- 4.0 yrs, weight 31.6 +/- 25.9 kg) with leukemia or other
      hematologic disease. INTERVENTIONS: Serum was sampled before and after a single 6
      mg/kg intravenous dose and after seven oral 3-mg/kg doses of fluconazole.
      MEASUREMENTS AND MAIN RESULTS: Mean (SD) pharmacokinetics were distribution half
      life 1.67 (1.25) hours, elimination half-life 15.62 (3.21) hours, total body
      clearance 0.63 (0.19) ml/min/kg, volume of distribution for the central
      compartment 0.56 (0.10) L/kg, volume of distribution at steady state 0.77 (0.12)
      L/kg, absorption half-life 0.41 (0.26) hour, and oral bioavailability 0.92
      (0.09). Volume of distribution for the central compartment was highly correlated
      with body surface area (r2 = 0.891) and weight (r2 = 0.949). Volume of
      distribution at steady state correlated with body surface area (r2 = 0.986), and
      total body clearance correlated with body surface area (r2 = 0.867). CONCLUSIONS:
      Fluconazole elimination was well described using a two-compartment model. Oral
      absorption was rapid and nearly complete. Children have a larger volume of
      distribution for the central compartment and faster elimination rate than adults.
      Body surface area and weight are important factors in determining
      pharmacokinetics in these patients.

PMID- 7739947
TI  - The effect of prophylactic nifedipine on renal function in patients administered
      contrast media.
AB  - STUDY OBJECTIVE: To determine if prophylaxis with nifedipine could decrease the
      frequency of contrast medium-induced renal impairment. DESIGN: Prospective,
      randomized clinical trial. SETTING: A university-affiliated hospital. PATIENTS:
      Patients undergoing scheduled radiologic examinations involving infusion of
      contrast media. INTERVENTIONS: Forty-two patients were randomized to receive
      nifedipine 10 mg orally 1 hour before the imaging procedure, and 43 to receive no
      treatment. MEASUREMENTS AND MAIN RESULTS: Baseline serum creatinine levels were
      compared with maximum levels 24 and 48 hours after administration of contrast
      medium. No statistically significant difference was seen in either the mean
      change or mean percentage change in serum creatinine between the control and
      nifedipine groups. The mean changes in serum creatinine were +7.4 mumol/L in the
      control group and +2.7 mumol/L in the nifedipine group (p = 0.33); the mean
      percentage changes were +10.2% and +4.8%, respectively (p = 0.54). CONCLUSION:
      Regardless of statistical analysis, it is unlikely that elevations in serum
      creatinine of this magnitude (< 0.1 mg/dl) are of clinical significance. We
      therefore conclude that prophylactic nifedipine is not clinically beneficial in
      preserving renal function in patients receiving contrast medium and that the
      agent should not be routinely administered for this purpose.

PMID- 7739948
TI  - Sepsis syndrome and associated sequelae in patients at high risk for gram
      negative sepsis.
AB  - We conducted a prospective surveillance study of 80 hospitals across the United
      States to determine the incidence of sepsis syndrome and its associated sequelae
      in hospitalized patients over age 18 years who were administered antibiotics for
      suspected or documented gram-negative infection. A sample of 1754 hospitalized
      patients were followed from onset of antimicrobial therapy to discharge or death.
      Mortality rates (MR) varied depending on the suspected source of sepsis syndrome.
      For patients in whom the syndrome was associated with community-acquired urinary
      tract infections, mortality was 20% (relative risk [RR] = 0.51, p < 0.05), for
      those with trauma 20.6% (RR = 0.51, p < 0.05), and patients with nosocomial
      respiratory tract infections 57.1% (RR = 1.66, p < 0.05). More than two
      complications occurred in 65.2% of patients under age 60 years (MR 31%), 40.8% of
      those age 60-80 (MR 42%), and 35.6% of patients older than 80 years (MR 33.3%, p
      > 0.05). Various patient populations had significant differences in both the
      incidence of the syndrome and its complications, and consequent mortality.
      Perhaps morbidity as well as mortality should be used as outcomes when testing
      the efficacy of innovative therapies for sepsis.

PMID- 7739949
TI  - Is antidepressant use changing? Prevalence and clinical correlates in two New
      England communities.
AB  - We attempted to determine whether the prevalence of antidepressant use had
      increased in population-based samples between 1981 and 1993, and compared the
      characteristics of antidepressant users and nonusers. Data were derived from six
      biennial, random sample, cross-sectional household surveys conducted between 1981
      and 1993 in two southeastern New England communities. For each survey, point
      prevalence estimates were determined for the major antidepressant categories.
      Antidepressant users were most likely to be women, slightly older, and less
      likely to be employed than nonusers (p < 0.0001). Comorbid conditions and
      concurrent drug therapy were present more frequently among users. The overall
      prevalence of antidepressant use per 1000 population increased from 7.8 (95%
      confidence interval 4.3, 11.3) in 1981-1982 to 31.4 (95% CI 23.9, 38.9) in 1992
      1993, especially among women and respondents between ages 40 and 59 years.

PMID- 7739950
TI  - Association of vancomycin serum concentrations with outcomes in patients with
      gram-positive bacteremia.
AB  - We attempted to determine if an association exists between vancomycin serum
      concentrations resulting from traditional dosing regimens, and efficacy and
      toxicity outcomes. We reviewed the medical charts of 273 consecutive patients
      prescribed 273 courses of vancomycin therapy for documented, gram-positive
      bacteremia. Of the 273 courses of therapy, 45 and 31 patients met all criteria
      and were evaluated for toxicity and efficacy, respectively. The duration of fever
      and abnormal white blood cell counts, length of hospital stay, overall mortality,
      serum creatinine, and serum vancomycin concentrations were evaluated
      retrospectively. No association between initial peak or trough levels with
      mortality was noted. However, patients were more likely to become afebrile within
      72 hours if peak and trough concentrations were 20 micrograms/ml or greater and
      10 micrograms/ml or greater, respectively (p < 0.01). Patients were also more
      likely to have their white blood cell count return to normal within 72 hours if
      trough concentrations were 10 micrograms/ml or above (p < 0.01). No statistically
      significant correlation between nephrotoxicity and initial serum creatinine, days
      of hospital stay, or days of vancomycin therapy were found. Serum concentrations
      of vancomycin, assessed before the development of nephrotoxicity, were
      significantly higher in patients who became nephrotoxic. Mean (SD) trough
      concentrations were 23.2 (2.5) micrograms/ml and 10.2 (3.8) micrograms/ml in
      nephrotoxic and nonnephrotoxic patients, respectively. Our results suggest that
      the commonly accepted therapeutic range for vancomycin trough concentrations (<
      10 micrograms/ml) may be too restrictive in patients receiving vancomycin therapy
      alone.

PMID- 7739951
TI  - Effects of pravastatin on plasma lipid concentrations in poloxamer 407-induced
      hyperlipidemic rats.
AB  - A new animal model of hyperlipidemia is being developed using the nonionic
      surfactant poloxamer 407 (P-407). We investigated the impact of pravastatin on P
      407-induced hyperlipidemia. Twenty rats received P-407 300 mg intraperitoneally
      to induce hyperlipidemia, and 20 control rats received saline injection.
      Pravastatin was administered orally to an equal number of rats in both groups
      using three different regimens. A fourth group did not receive pravastatin. At 24
      hours after injection, total cholesterol levels in two of the pravastatin groups
      were 28% and 34% lower than those in animals that did not receive pravastatin (p
      < or = 0.01). At 48 hours, triglyceride levels were significantly lower in all
      pravastatin groups (21-44%) versus animals not receiving pravastatin. Pravastatin
      diminished the effects of P-407 on lipoproteins. This new animal model may be
      useful in screening for investigational antihyperlipidemic agents.

PMID- 7739952
TI  - Rewards and advancements for clinical pharmacy practitioners. American College of
      Clinical Pharmacy.
AB  - It is important to recognize that pharmacy practice models are changing quickly.
      Although the concepts of pharmaceutical care depict all pharmacists as clinical
      practitioners, there are still significant opportunities for individuals to
      develop advanced and refined skills and knowledge, and to seek recognition.
      Criteria for professional advancement need to be reevaluated and modified
      periodically. As departments become more effective in implementing pharmaceutical
      care, and practice skills advance, criteria for advancement must be updated.
      Recognition and advancement within newer models of practice such as patient focus
      units, clinical path teams, and quality improvement teams complicate assessment
      and evaluation strategies. In the future, pharmacy managers will need to look at
      reward and advancement systems that incorporate the recommendations of the team
      manager or members for these newer models of practice. Perhaps there will be a
      shift in responsibility for recognition to the team manager. Career ladders may
      need to provide for new roles, and reward practitioners for behaviors not
      currently represented in most departmental performance evaluations. Performance
      evaluation, standards of practice, and advancement criteria will need to be
      carefully reviewed and integrated with the patient focus team's objectives,
      structure, and processes to assure that appropriate recognition is given to
      pharmacists in this exciting new environment. Career ladders provide one form of
      reward and advancement for practitioners. Institutions can include many elements
      of career ladder process, function, and structure, as well as implement many
      other management tools for reward and recognition, without implementing a
      complete career ladder.

PMID- 7739953
TI  - Clinical predictors of computed tomographic abnormalities following pediatric
      traumatic brain injury.
AB  - Children commonly seek attention in emergency departments following head injury.
      Head computed tomography (CT) is often used to decide subsequent disposition.
      Clinical criteria predicting CT abnormalities would allow effective and timely
      treatment and minimize unnecessary procedures depleting overburdened medical
      resources. We prospectively compared presenting clinical features with subsequent
      emergent head CT in 300 children less than 19 years old over a nine-month period.
      The disposition of patients following imaging was also recorded. Only suspected
      abuse was more than 50% positively predictive in children below age two and those
      above age two. Two signs were more than 67% positively predictive in both age
      groups: focal motor deficit and pupillary asymmetry. Patients with abnormal CTs
      were the only children to undergo emergent neurosurgery (30%) and were nearly
      five times as likely to be intensively monitored. Children with normal CTs were
      nearly five times as likely to be observed in a routine department or at home. We
      conclude that no single clinical feature can predict with certainty an
      abnormality on immediate head CT. However, children suspected of being abused,
      and those with focal motor deficits or pupillary asymmetry, should be imaged.
      Finally, emergent CT when judiciously ordered likely reduces unforeseen morbidity
      and minimizes costly intensive care observation.

PMID- 7739954
TI  - Four-year review of cigarette ingestions in children.
AB  - The objective of our study was to assess the demographics, incidence, types of
      symptoms, and outcomes of cigarette product ingestions in children. The study was
      a retrospective database review. Seven hundred children under six years of age
      ingesting cigarettes or cigarette butts reported to a Poison Control Center
      between 1988 and 1991. Among 143 patients (20.4%) with symptoms, vomiting was the
      only symptom in 138 (98.6%) and occurred in less than 20 minutes in 104 (74.3%).
      The five remaining patients (two with vomiting, three without) developed
      transient lethargy or irritability that completely resolved. Forty-four of 700
      patients ingested potentially toxic amounts and were referred to the emergency
      department; three were lost to follow-up. Initially asymptomatic patients never
      developed symptoms. Symptomatic patients improved without sequelae. No patient
      developed seizures. We concluded that significant toxicity from the ingestion of
      cigarette products in children is rare. Vomiting within 20 minutes is the most
      common symptom. Its absence predicts a favorable outcome, even when large amounts
      are suspected to have been ingested.

PMID- 7739955
TI  - Transvenous right ventricular pacing during cardiopulmonary resuscitation of
      pediatric patients with acute cardiomyopathy.
AB  - We describe the cardiopulmonary resuscitation efforts on five patients who
      presented in acute circulatory failure from myocardial dysfunction. Three
      patients had acute viral myocarditis, one had a carbamazepine-induced acute
      eosinophilic myocarditis, and one had cardiac hemosiderosis resulting in acute
      cardiogenic shock. All patients were continuously monitored with central venous
      and arterial catheters in addition to routine noninvasive monitoring. An
      introducer sheath, a pacemaker, and sterile pacing wires were made readily
      available for the patients, should the need arise to terminate resistant cardiac
      dysrhythmias. All patients developed cardiocirculatory arrest associated with
      extreme hypotension and dysrhythmias within the first 48 hours of their admission
      to the pediatric intensive care unit (PICU). Right ventricular pacemaker wires
      were inserted in all of them during cardiopulmonary resuscitation (CPR). In four
      patients, cardiac pacing was used, resulting in a temporary captured rhythm and
      restoration of their cardiac output. These patients had a second event of cardiac
      arrest, resulting in death, within 10 to 60 minutes. In one patient, cardiac
      pacing was not used, because he converted to normal sinus rhythm by electrical
      defibrillation within three minutes of initiating CPR. We conclude that cardiac
      pacing during resuscitative efforts in pediatric patients suffering from acute
      myocardial dysfunction may not have long-term value in and of itself; however, if
      temporary hemodynamic stability is achieved by this procedure, it may provide
      additional time needed to institute other therapeutic modalities.

PMID- 7739957
TI  - Corneal abrasion in infants.

PMID- 7739958
TI  - Bilateral fibula fractures from infant walker use.

PMID- 7739956
TI  - Training, attitudes, and income profiles of pediatric emergency physicians: the
      results of a 1993 survey of the American Academy of Pediatrics Section on
      Pediatric Emergency Medicine.
AB  - In late 1993, 562 questionnaires were sent to members of the Emergency Medicine
      Section of the American Academy of Pediatrics; of the questionnaires sent, 65%
      (365) were returned. Data were collected on 280 full-time practicing pediatric
      emergency physicians (PEPs). Eighty-two percent of these full-time PEPs have been
      practicing pediatric emergency medicine for less than 10 years, and two thirds of
      them are males. The majority work in pediatric emergency departments, devoting
      28.1 clinical hours per week to their specialty. Ninety-nine percent of these
      full-time PEPs are board certified in pediatrics, and 61.5% are board certified
      in pediatric emergency medicine, whereas less than one quarter are fellowship
      trained. Approximately two thirds of these physicians feel that board
      certification in pediatric emergency medicine is a prerequisite for practicing;
      only one quarter feel that a fellowship in pediatric emergency medicine is
      required at this time. Average annual gross income for full-time PEPs was
      $111,000 per year; 62.8% of these physicians make more than $100,000 per year.
      PEPs indicated that diversity of their clinical practice and the medical acuity
      of their patients were the most desirable aspects of pediatric emergency
      medicine, whereas scheduling and the shift work nature of the profession, along
      with lack of follow-up in hospital practice, were seen as the least desirable
      aspects of the subspecialty.

PMID- 7739959
TI  - Acute appendicitis: a cause of recurrent abdominal pain in pediatric trauma.
AB  - When traumatic abdominal injury and acute appendicitis occur within a short
      period of time, the diagnosis can be difficult and may result in a delay in
      treatment of the appendicitis. We report the case of a four-year-old boy with
      documented intraabdominal injury from a motor vehicle crash who developed
      appendicitis while hospitalized and recovering from his injuries.

PMID- 7739960
TI  - Delayed onset lorazepam poisoning successfully reversed by flumazenil in a child.
      Case report and review of the literature.

PMID- 7739961
TI  - Chest pain and cardiomegaly without pulmonary involvement: an atypical
      presentation of pediatric mycobacterial disease.

PMID- 7739962
TI  - Management of coin ingestion: any change?
AB  - Figure 1 summarizes the recommendations for treatment of coin ingestion. Serious
      complications from coin ingestion are extremely rare and are usually found in
      children who unknowingly ingest a coin. The recommendations from the literature
      concerning the treatment of children with a history of coin ingestion, such as
      obtaining radiographs on all such children, may not accurately reflect the
      current practices of emergency physicians. It would be of interest to survey
      emergency physicians to examine actual practices in the management of coin
      ingestion.

PMID- 7739963
TI  - The abstract and the academic clinician.
AB  - The abstract is an essential element of all phases of the research process-
      submission of proposals for funding, presentation at scientific meetings, and
      ultimately, publication. Thus, the writing of effective abstracts is an important
      skill for the academic clinician. Like all skills, it requires significant time
      and effort for its acquisitions and practice for its maintenance. The structured
      abstract provides guidance for both format and content, and is an important
      innovation.

PMID- 7739964
TI  - Acute renal failure.

PMID- 7739965
TI  - Controversial issues.

PMID- 7739966
TI  - An infant fatality associated with inspiratory and expiratory wheezing: another
      wheeze that wasn't asthma.
AB  - The physician who encounters an infant with respiratory distress associated with
      inspiratory stridor and expiratory wheezing should maintain an expanded
      differential diagnosis. Hypocalcemia should be included in the differential
      diagnosis for biphasic wheezing. Failure to consider this entity may lead to
      adverse patient outcome.

PMID- 7739967
TI  - Prehospital fluid therapy in pediatric trauma patients.
AB  - In order to evaluate the impact of prehospital intravenous fluid therapy on the
      outcome of pediatric trauma patients and to evaluate the effect of such therapy
      on the on-scene interval, we performed a retrospective chart review of 50
      pediatric trauma patients less than 18 years old transported directly from the
      field by Emergency Medical Services personnel with an intravenous catheter in
      place and admitted to the Trauma Service of a level I urban pediatric trauma
      center. As judged by an expert panel using a new grading system, prehospital
      intravenous fluid therapy was inconsequential to outcome in 47 of 50 patients,
      possibly beneficial in two of 50 patients, and possibly detrimental in one of 50
      patients. Patients who received their catheters at the scene had significantly
      longer on-scene intervals than those who received them in the ambulance (15.4 vs
      11.4 minutes, P < 0.05). The mean volume of fluid administered was 4.4 ml/kg body
      weight. Placement of the catheter (at the scene vs in the ambulance) and
      prehospital fluid volume administered were independent of the Injury Severity
      Score. The role of prehospital fluid therapy in pediatric trauma patients in an
      urban setting requires reevaluation.

PMID- 7739968
TI  - Childhood injuries and the importance of documentation in the emergency
      department.
AB  - The purpose of this study is 1) to evaluate the extent to which documentation of
      the medical record is completed for dependent children who present for evaluation
      of an acute injury, and 2) to examine the factors that favorably or adversely
      influence completion of the medical record. The emergency department (ED) ledgers
      of 669 children less than nine years of age were reviewed, including 172 (25.7%)
      who presented for evaluation of an acute injury. Each of the latter charts was
      examined for basic demographic data, as well as information about injury type and
      mechanism, ED provider, and involvement of social services personnel. The ledgers
      were further examined to determine completeness of chart documentation in several
      relevant areas, including the circumstances and characteristics of the acute
      injury, pertinent past medical history, and course of management and referral
      while in the ED. Each of 15 individual documentation variables was assigned a
      score of either zero (incompletely/not addressed or documented) or one
      (completely addressed or documented). The 15 individual scores were equally
      weighted and summed, resulting in a total documentation score ranging from zero
      (failure to address or document any of the 15 variables) to 15 (all variables
      completely addressed/documented). The mechanisms of injury included falls from
      height (48.3%), direct blunt impact other than falls (26.7%), penetrating injury
      (6.4%), burn (5.2%), and ingestion (8.1%). Seventeen patients (9.9%) were
      admitted for primarily medical, and one (0.6%) for primarily social, indications;
      one patient died as a result of his injuries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7739969
TI  - Colorimetric end-tidal carbon dioxide detector.

PMID- 7739970
TI  - Case 01-1995: a two-year-old female with alteration of consciousness.

PMID- 7739971
TI  - Emergency department visits by children with sickle hemoglobinopathies: factors
      associated with hospital admission.
AB  - Children with sickle cell disease frequently present to the emergency department
      (ED) for evaluation of fever or management of pain. We retrospectively analyzed
      all ED visits by children with sickle hemoglobinopathies during 1990, excluding
      those for trauma. Of 146 visits by 56 children, 73 (50%) were classified as
      "Painful Events," 43 (29%) as "Febrile Events," 20 (14%) as "Painful and Febrile
      Events," and 10 (7%) as "Other." Hospital admission occurred for 42% of Painful
      Events versus 70% of Febrile Events (P = 0.008) and 85% of Painful and Febrile
      Events (P = 0.002). For Painful Events, location of pain was not associated with
      hospitalization, but pain less than 24 hours in duration before the ED visit (P =
      0.002) and administration of intravenous fluids and analgesia (P = 0.001) were
      associated with admission. For children evaluated for Febrile Events, age less
      than six years (P = 0.016) and maximum temperature greater than 39 degrees C (P =
      0.011) were associated with subsequent hospitalization, but total white blood
      cell count and absolute neutrophil count were not. For Painful and Febrile
      Events, pain less than 24 hours (P = 0.029) was associated with hospital
      admission, but age, maximum temperature, white blood cell count, and absolute
      neutrophil count were not. Although prospective studies are needed to validate
      these data, the identification of factors predictive of hospital admission should
      expedite ED care to sickle cell patients.

PMID- 7739973
TI  - Formulas for the healthy term infant.

PMID- 7739972
TI  - Acute renal failure: diagnosis.

PMID- 7739974
TI  - Ataxia.

PMID- 7739975
TI  - Craniosynostosis.

PMID- 7739976
TI  - Index of suspicion. Case 1. Diagnosis: ureterocele.

PMID- 7739977
TI  - Index of suspicion. Case 2. Diagnosis: peritonsillitis.

PMID- 7739978
TI  - Index of suspicion. Case 3. Diagnosis: pneumococcal pneumonia.

PMID- 7739979
TI  - Penicillin update.

PMID- 7739980
TI  - Normal speech and language development: an overview.

PMID- 7739981
TI  - Use of primary caretakers as proxies to measure the health care needs of patients
      with AIDS.
AB  - This study evaluated the validity of patient-proxy responses to the Healthcare
      Needs Scale for Patients with HIV/AIDS. This scale measures environmental and
      psychosocial support, financial resources, health behaviors, social support, and
      health management. A sample of 35 patients with HIV/AIDS and their primary
      caretakers was selected from a hospital inpatient AIDS unit in Baltimore,
      Maryland, between 1990 and 1992. The significance of discrepancies between the
      patient and caretaker responses was tested with Wilcoxon's matched pairs/signed
      ranks test. None of the 19 scale items exhibited a significant Z statistic. It
      was concluded that the primary caretakers of PWAs can serve as informed proxies
      and provide accurate information on the patients' healthcare needs.

PMID- 7739982
TI  - Reliability and validity of the Smoking and Women Questionnaire among three
      ethnic groups.
AB  - Cigarette smoking among women continues to be a major health risk to the smoker
      and to those around her. Programs aimed at stopping and maintaining smoking
      cessation have had very limited success due in part to the failure to
      individualize smoking cessation programs based on specific characteristics of the
      smoker. This study presents reliability and validity of a 14-item questionnaire
      developed to determine the readiness of women from three ethnic groups (non
      Hispanic white, black American, and Hispanic American) to stop smoking. The
      Smoking and Women Questionnaire (SWQ) consists of items representative of core
      elements conceptualized in the Smoking/Ex-smoking Model for Women. The core
      factors are: beliefs/attitudes toward smoking, sociability, stress, coping, self
      efficacy, motivation, nicotine dependence, and support. The SWQ was completed by
      both smoking and nonsmoking non-Hispanic white (N = 233), smoking and nonsmoking
      black American (N = 70), and smoking and nonsmoking Hispanic American (N = 73)
      women. The test-retest correlation coefficient over a one- to three-week period
      (N = 53) was .84. Cronbach alphas for whites, blacks, Hispanics, and combined
      groups were .81, .85, .84 and .83, respectively. Content validity was shown by
      experts who agreed that the core elements were represented in the SWQ. Construct
      validity was shown for ethnic groups separately and combined in that smokers had
      significantly lower SWQ scores than nonsmokers. Items representative of the core
      elements were rated by smokers in a similar manner irrespective of ethnicity,
      suggesting similar attitudes and behaviors toward smoking. Further research is
      needed to determine if the SWQ can predict readiness of women to stop smoking and
      serve as a basis for developing individualized smoking cessation programs.
      Implications for smoking cessation programs are reviewed.

PMID- 7739983
TI  - The contributions of sleep to perceived health status during adolescence.
AB  - The purposes of this correlational study were to examine the relationships of
      three dimensions of sleep quality (sleep disturbance, sleep effectiveness, and
      sleep supplementation) and sleep quantity (the amount of sleep obtained per day)
      to perceived health status in early, middle, and late adolescents. The samples
      consisted of 106 early adolescents (aged 12 to 14), 111 middle adolescents (aged
      15 to 17), and 113 late adolescents (aged 18 to 21). In classroom settings, all
      subjects completed the VSH Sleep Scale, which measures sleep disturbance, sleep
      effectiveness, and sleep supplementation (the amount of sleep per day was
      calculated from two items on the scale); the General Health Rating Index, which
      measures perceived health status; and a demographic data sheet. Pearson product
      moment correlation coefficients between the sleep variables and perceived health
      status were not statistically significant for early and late adolescents. For
      middle adolescents, however, the correlations between sleep disturbance and
      perceived health status, between sleep effectiveness and perceived health status,
      and between amount of sleep per day and perceived health status were
      statistically significant, but the correlation between sleep supplementation and
      perceived health status was not. A post hoc regression analysis indicated that
      the sleep variables explained a small, but statistically significant, amount of
      variance in perceived health status for middle adolescents. Findings are
      discussed in light of theories guiding the study, and implications for nursing
      practice are addressed.

PMID- 7739984
TI  - Kansans' perceptions of health care reform: a qualitative study on coming to
      public judgment.
AB  - The purpose of this study was to analyze the discussion of participants from
      three Kansas town meetings on health care reform. Yankelovich's process of
      "coming to public judgment" was used to guide the research. In this study
      participants were in the process of the first two stages of public judgment:
      consciousness-raising and working through. Health care reform was described in
      six themes: access, bureaucracy, distribution, expectations, futility, and
      prevention. Health care needs and reform were described within the context of
      personal meaning for those attending the town meetings.

PMID- 7739985
TI  - Ensuring public health nursing in managed care: partnerships for healthy
      communities.

PMID- 7739986
TI  - Policy research: lessons from the field.
AB  - Nursing's involvement in policy development has become a standard and expected
      part of nursing practice. One avenue of involvement, policy research, is
      clarified through description and case example. Policy research is described as
      context-driven, multimethodological, and time-sensitive. Considering these
      essential characteristics when planning and implementing policy research enhances
      nursing's ability to positively influence the policy process. A case example of
      policy research from the criminal justice system evaluated the effectiveness of a
      diversion program with alcohol and marijuana misdemeanants (N = 1,239). The
      purposes of the study were to describe the percentage of diversion participants
      with alcohol or marijuana-possession charges who were successful in completing
      the diversion program and to examine the incidence of subsequent arrests on
      alcohol or marijuana-possession charges among those who successfully completed
      the program. The case example demonstrates the intricate and unique relationship
      between research and the policy arena. Policy research can equip nursing to enter
      policy debates with data and to participate as a persuasive agent of social
      change.

PMID- 7739987
TI  - The Howard Association of New Orleans--precursor to district nursing.
AB  - Although philanthropist William Rathbone is generally recognized as the founder
      of district nursing (in Liverpool, England, in 1859), the Howard Association of
      New Orleans actually began to use a pattern of district nursing 26 years earlier
      as a response to yellow fever epidemics. Concepts brought forth by the
      association included dividing the city into districts; teaching preventive
      measures; using community members to locate those needing assistance; and caring
      for the sick in their homes, utilizing nurses when the need arose.

PMID- 7739988
TI  - A concept analysis of home visiting.
AB  - Throughout the history of community health nursing, home visiting has been and
      remains a central nursing intervention. Yet little conceptual clarification has
      dealt with this intuitively very valuable nursing intervention. Here, the concept
      of home visiting was investigated through a concept analysis. The nature of home
      visiting as it emerged over time was gleaned from historical and current
      literature. A working definition, capturing the essence of home visiting and
      implying new measurement possibilities, was formulated. Home visiting emerged as
      a specific nursing intervention, preceded by an antecedent event, unfolding as a
      process, with phases labeled as "contacting," "going to see," "gaining entry,"
      "seeing," "terminating," and "telling." Nurse sub-outcomes, nursing strategies,
      contextual factors influencing the process, and potential consequences of home
      visiting were uncovered.

PMID- 7739989
TI  - Discharge planning from home health care and patient status post-discharge.
AB  - An exploratory study of 57 elderly patients discharged from home health agencies
      sought to identify how they and their caregivers were prepared for discharge and
      how they were managing. Data were collected from the home care records and post
      discharge interviews with patients and caregivers. Results indicate little
      evidence of formal discharge planning. However, home care records appear to
      underreport what home care staff do. On follow-up, over half of the patients had
      improvement in their health, two-thirds were independent in activities of daily
      living, and few patients had need of formal services.

PMID- 7739990
TI  - A description of the gender differences in risk behaviors in young adults with
      genital herpes.
AB  - The purpose of this paper is to describe gender differences in risk behaviors-
      substance use and sexual behavior--in young adults with genital herpes. Two
      hundred fifty-two young adults with genital herpes were recruited into the study
      via newspaper advertisements in a West Coast metropolitan area. As a part of a
      large randomized clinical trial, participants completed questionnaires measuring
      demographic characteristics and the risk behaviors of substance use and sexual
      behavior. Participants had a mean age of 27.1 years and were largely Caucasian,
      employed, college-educated, and heterosexual. Women were two years younger than
      men and had less income. Gender differences were found in both substance use and
      sexual behavior. Men were more likely to report current use of illicit drugs than
      were women. Men were also more likely to report a history of gonorrhea, and
      urethral discharge. Women reported initiating sex at an older age and having
      fewer sexual partners over their lifetimes than men. There were no gender
      differences in use of condoms or spermicides specifically to prevent transmission
      of genital herpes. Further study is needed of these young adults as they are at
      high risk for transmission of the disease and also for contracting other sexually
      transmitted diseases (STDs), including human immunodeficiency virus (HIV)
      infection. Sensitive interventions are needed with this high-risk population.

PMID- 7739991
TI  - Rapid prenatal diagnosis of 14 cases of triploidy using fish with multiple
      probes.
AB  - Fluorescence in situ hybridization (FISH) of chromosome-specific probes to
      interphase nuclei can rapidly identify aneuploidies in uncultured amniotic fluid
      cells. Using DNA probe sets specific for chromosomes 13, 18, 21, X, and Y, we
      have identified 14 fetuses where the hybridization pattern was consistent with a
      triploid chromosome constitution. In each case, the identification of fetal
      abnormalities by ultrasound examination initiated a request for rapid
      determination of ploidy status via prenatal FISH analysis of uncultured
      amniocytes. FISH produced a three-signal pattern for the three autosomes in
      combination with signals indicating an XXX or XXY sex chromosome complement. This
      hybridization pattern was interpreted to be consistent with triploidy. Results
      were reported to the physician within 2 days of amniocentesis and subsequently
      confirmed by cytogenetics. These cases demonstrate the utility of FISH for rapid
      prenatal identification of triploidy, particularly when fetal abnormalities are
      seen with ultrasonographic examination.

PMID- 7739992
TI  - Genetic amniocentesis in biamniotic twin pregnancies by a single transabdominal
      insertion of the needle.
AB  - We present a technique to aspirate amniotic fluid from both sacs in biamniotic
      twin pregnancies using a single abdominal insertion with a spinal needle. It was
      successful in 48 out of 55 cases of biamniotic twin pregnancies referred to our
      perinatal unit between 1985 and 1994. The single insertion technique was used
      when the inter-amniotic membrane was clearly evident and two separate free
      amniotic fluid pools could be reached by the operator with a single puncture. An
      adequate amount of amniotic fluid was sampled from both sacs to make a
      cytogenetic diagnosis in all cases. There were four fetuses with trisomy 21 in
      three twin pregnancies. In two cases, only one twin was affected whilst the co
      twin was normal, so that a selective feticide was performed. No miscarriages due
      to genetic amniocentesis were reported. After 1990, all genetic amniocenteses in
      biamniotic twin pregnancies (except for one case due to late booking) were
      performed between 14 and 15 weeks of gestation and with all cases except one, it
      was possible to sample both twins by a single puncture. We suggest that early
      amniocentesis (14-15 weeks) by a single abdominal puncture could be a reliable
      and safe alternative to first-trimester chorionic villus sampling in twin
      pregnancies.

PMID- 7739993
TI  - Identification of abnormal chromosomal complement in formalin-fixed, paraffin
      embedded placental tissue.
AB  - The objective of this project was to assess the efficacy of fluorescence in situ
      hybridization (FISH) with chromosome-specific DNA probes to identify chromosome
      number in formalin-fixed, paraffin-embedded placental specimens. Using this
      approach, 75 per cent of the karyotypes in 20 formalin-fixed placental samples
      (comprising aneuploids, triploids, and normals) were correctly identified. As
      this technology improves, the ability to obtain information regarding chromosomal
      abnormalities in formalin-fixed, paraffin-embedded placental tissue should
      improve as well. This technology can potentially provide important cytogenetic
      information even when fresh tissue is not available for standard karyotypic
      analysis.

PMID- 7739994
TI  - Prenatal diagnosis of spinal muscular atrophy in Russia.
AB  - Ninety-two families with spinal muscular atrophy (SMA) applied for genetic
      counselling and further prenatal diagnosis. To minimize expenses, only one
      tightly linked informative marker was determined in the course of preliminary
      examination, and non-radioactive allele detection was preferably used. Four
      prenatal diagnoses of SMA type I, four of SMA type II, and one of SMA type III
      were made. This trial programme shows the considerable requirements, importance,
      and potential effectiveness of prenatal prediction of SMA in Russia.

PMID- 7739995
TI  - Molecular evidence of fetal-derived chromosome 21 markers (STRs) in transcervical
      samples.
AB  - Transcervical cells (TCCs), collected by flushing or aspiration at 8-13 weeks of
      gestation, were analysed for the presence of fetal-derived DNA sequences. DNA
      extracted from maternal peripheral blood, TCC samples, and placental tissue was
      amplified by the polymerase chain reaction (PCR) to detect small tandem repeat
      (STR) markers specific to chromosome 21. STR products of fetal origin could be
      clearly observed in four TCC samples. TCC samples collected by flushing or
      aspiration were also analysed by fluorescent in situ hybridization (FISH) using X
      and Y probes simultaneously: 46,XY cells could be detected in all TCC samples
      obtained from mothers with male fetuses.

PMID- 7739996
TI  - Mosaicism of autosomes and sex chromosomes in morphologically normal, monospermic
      preimplantation human embryos.
AB  - We have previously detected chromosome abnormalities in human embryos whilst
      identifying the sex for preimplantation diagnosis of X-linked disease. In this
      study we assess the incidence of these abnormalities, both for sex chromosomes
      and autosomes 1 and 17, using dual fluorescent in situ hybridization (FISH).
      Sixty-nine normally fertilized embryos of good morphology at the 6-10 cell stage
      (day 3 post-insemination) were examined. The embryos were spread whole using HCl
      and Tween 20 to dissolve the cytoplasm. Thirty-four embryos were analyzed for the
      sex chromosomes and 35 for autosomes 1 and 17. All probes were directly labelled
      with fluorochromes allowing analysis in 2 h. Control lymphocytes demonstrated
      that the probes were of high specificity. For the sex chromosomes, five embryos
      were mosaic (15 per cent) with the remaining 29 being uniformly XX or XY. In no
      case was an XX nucleus found in an otherwise XY embryo, indicating that even
      though mosaicism for the sex chromosomes is present, such abnormalities would not
      lead to a misdiagnosis of sex. For the autosomes, 16 embryos were abnormal (46
      per cent); one embryo was triploid, one was monosomic for chromosome 1, and ten
      others were diploid mosaics (three diploid/aneuploid, three diploid/polyploid,
      and four diploid/haploid). A further four embryos had variable chromosome numbers
      in the majority of nuclei which appeared to be the result of uncontrolled mitotic
      division. The presence of haploidy or double monosomy, which occurred in 15 per
      cent of nuclei, has important implications for the diagnosis of trisomies and
      dominant disorders.

PMID- 7739997
TI  - Retrospective study of trisomy 18 in chorionic villi with fluorescent in situ
      hybridization on archival direct preparations.
AB  - Trisomy 18 in direct chorionic villus preparations needs further investigation
      since the chromosome abnormality may be confined to the placenta and may not
      represent the actual fetal karyotype. We performed, retrospectively, fluorescent
      in situ hybridization (FISH) with the chromosome 18 centromere probe (L1.84) on
      interphase nuclei of destained slides of all cases of full trisomy 18 (n = 22)
      and mosaic trisomy 18 (n = 8) detected among 7600 first-trimester chorionic
      villus samples during an 8-year period (1985-1992). More nuclei displaying three
      signals were encountered in cases of full and mosaic trisomy 18 confirmed in
      fetal tissue than in non-confirmed cases. FISH can be useful for the verification
      of trisomy 18 in direct chorionic villus preparations.

PMID- 7739998
TI  - Prenatal ultrasound diagnosis of gastric outlet obstruction due to a pyloric web.
AB  - Gastrointestinal tract atresia has an incidence of 1 in 10,000 live-births, while
      gastric outlet obstruction comprises only approximately 1 per cent of these
      malformations. A prenatally diagnosed case is described, followed by a discussion
      regarding the diagnosis and possible associated abnormalities.

PMID- 7739999
TI  - Twin-twin transfusion syndrome--possible roles for Doppler ultrasound and
      amniocentesis.
AB  - A 29-year-old woman was referred for suspicion of twin-twin transfusion syndrome
      (TTTS). Several ultrasonographic and neonatal criteria of TTTS were encountered
      in this twin pregnancy. The peculiar observations in this case were, firstly, the
      demonstration of superficial anastomosis by Doppler ultrasound and, secondly,
      that one single therapeutic amniocentesis could have been sufficient to partially
      correct the progression of the syndrome, as after amniocentesis it was no longer
      possible to demonstrate the vascular communication. This observation suggests
      that superficial anastomoses could also have a role in the genesis of TTTS. Their
      effect could be monitored by Doppler ultrasound and could be more easily
      corrected by therapeutic amniocentesis.

PMID- 7740000
TI  - Prenatal diagnosis of 46,XX/47,XXY mosaicism: a case report.
AB  - A case of 46,XX/47,XXY mosaicism was diagnosed at 22 gestational weeks by
      amniocentesis and fetal blood sampling. After genetic counselling, the couple
      elected to have the pregnancy terminated. Culture of the fetal skin and both
      gonads confirmed the prenatal diagnosis. In external appearance, the abortus had
      no remarkable findings except hypospadia. Histology of both gonads showed
      testicular tissue without evidence of ovarian components.

PMID- 7740001
TI  - Macroglossia: prenatal ultrasonographic diagnosis and proposed management.
AB  - A case in which macroglossia was the sole unusual prenatal sonographic finding in
      a fetus affected with trisomy 21 is presented. The differential diagnosis of
      fetal macroglossia is given, emphasizing its strong relationship to fetal
      aneuploidy, together with the principles for evaluation and management.

PMID- 7740002
TI  - Ultrasonographic scanning of placental thickness and the prenatal diagnosis of
      homozygous alpha-thalassaemia 1 in the second trimester.
AB  - In order to evaluate the association between placental thickness (PT) and fetal
      homozygous alpha-thalassaemia 1 before the appearance of classic ultrasound
      findings of haemoglobin (Hb) Bart's hydrops fetalis, a total of 473 pregnancies
      were collected. The control group included 422 normal pregnancies with a
      gestational age from 14 to 23 weeks and the study group included 51 affected
      fetuses in the same gestational period. Fetal biparietal diameter (BPD) and PT
      were measured by high-resolution ultrasound. PT was evaluated against BPD. In the
      control group, the PT generally increased in parallel with the advancement of
      gestational age. All PT measurements in the study group were above the mean PT of
      their respective gestational week in the control group. Forty-six (90 per cent)
      of the pregnancies in the study group had PT larger than the mean plus two
      standard deviations of the control group. This study suggests that ultrasound
      measurement of PT may be a useful aid in the prenatal diagnosis of Hb Bart's
      hydrops fetalis before its classic findings become apparent in the late second
      trimester or third trimester.

PMID- 7740003
TI  - Exencephaly in autosomal dominant brachydactyly syndrome.
AB  - Exencephaly was diagnosed at 17 weeks in a 27-year-old primigravida with
      abnormalities of the hands and a family history suggestive of autosomal dominant
      brachydactyly and clinodactyly. In this family there was also a history of
      'anencephaly'. To our knowledge, this is the first report on the association of
      exencephaly and autosomal dominant brachydactyly. As the relationship between
      hand and cranial anomalies is well established, we suggest that this association
      in our case could be due to a defect in the same gene.

PMID- 7740004
TI  - Development of non-invasive fetal DNA diagnosis from maternal blood.
AB  - Several attempts have been made to detect and retrieve fetal nucleated cells
      including nucleated erythrocytes (NRBCs), leukocytes, and trophoblasts in
      maternal blood. We have recently developed a new method for non-invasive fetal
      DNA diagnosis from maternal blood. Peripheral blood granulocytes including NRBCs
      were isolated by a discontinuous density gradient method using Percoll
      (Pharmasia). NRBCs were found and retrieved at a single cell level using a
      micromanipulator under a microscope. To determine whether the origin of the NRBCs
      was maternal or fetal, the NRBCs were analysed by polymerase chain reaction (PCR)
      amplification to determine the presence of a Y-chromosome-specific repeat
      sequence in mothers carrying male fetuses. We were successful in predicting fetal
      sex accurately in 10 out of 11 samples taken from maternal blood. This new
      technique opens up fetal DNA diagnosis from maternal blood during the first
      trimester of pregnancy to the whole population because there is no risk to the
      fetus or the mother.

PMID- 7740005
TI  - Mid-trimester fetal sex determination from maternal peripheral blood by
      fluorescence in situ hybridization without enrichment of fetal cells.
AB  - To determine the fetal sex on 30 women who were 16-20 weeks pregnant, about
      100,000 maternal blood nucleated cells were analysed by means of fluorescence in
      situ hybridization (FISH) with a Y-chromosome-specific DNA probe. Cells with the
      hybridization signal were detected in 12 of the 30 women. All the 12 mothers gave
      birth to a male child. Of the other 18 women who had no Y-positive cells in the
      peripheral blood, 14 gave birth to a female child and four gave birth to a male
      child. These false-negative results probably occurred because the number of cells
      examined was inadequate. The data obtained in this study suggest that fetal sex
      determination using maternal peripheral blood with FISH is possible and that this
      diagnostic method will be clinically useful when more cells are analysed.

PMID- 7740006
TI  - Prenatal diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in a
      family with a previous fatal case of sudden unexpected death in childhood.
AB  - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a potentially fatal
      inherited disease with a carrier frequency of approximately 1:100 in most
      Caucasian populations. The disease is implicated in sudden unexpected death in
      childhood. A prevalent disease-causing point mutation (A985G) in the MCAD gene
      has been characterized, thus rendering diagnosis easy in the majority of cases.
      Since the clinical spectrum of MCAD deficiency ranges from death in the first
      days of life to an asymptomatic life, there are probably other genetic factors-
      in addition to MCAD mutations--involved in the expression of the disease. Thus,
      families who have experienced the death of a child from MCAD deficiency might
      have an increased risk of a seriously affected subsequent child. In such a family
      we have therefore performed a prenatal diagnosis on a chorionic villus sample by
      a highly specific and sensitive polymerase chain reaction (PCR) assay for the
      G985 mutation. The analysis was positive and resulted in abortion. We verified
      the diagnosis by direct analysis on blood spots and other tissue material from
      the aborted fetus and from family members.

PMID- 7740007
TI  - De novo deletions of the 5q13 region and prenatal diagnosis of spinal muscular
      atrophy.

PMID- 7740008
TI  - Late-onset isolated cystic hygroma. A first clinical sign of Proteus syndrome.

PMID- 7740010
TI  - Current awareness in prenatal diagnosis.

PMID- 7740009
TI  - Prenatal diagnosis and long survival of Fryns syndrome.

PMID- 7740011
TI  - Predictors of smoking during and after pregnancy: a survey of mothers of
      newborns.
AB  - BACKGROUND: Cigarette smoking during pregnancy represents a significant health
      risk to the fetus, but most women continue to smoke during pregnancy, and most
      who quit relapse postpartum. This study provides an assessment of psychosocial
      variables on women who quit, relapsed, cut down, or did not alter their smoking
      during pregnancy. METHODS: Mothers of newborns in 49 pediatric practices (N =
      13,495) were surveyed at the newborns' first well-care office visit to a
      pediatrician, and 2,901 mothers who smoked in the month prior to pregnancy were
      identified. Predictive information was obtained by comparing mothers who quit
      smoking with those who continued to smoke, mothers who stayed quit with
      relapsers, and mothers who reduced tobacco consumption with those who did not.
      RESULTS: Thirty-five percent of mothers reported quitting smoking during
      pregnancy, and 52% had cut down for pregnancy. Factors related to quitting
      smoking for pregnancy were younger age, higher level of education, lower smoking
      level, having a partner who did not smoke, and not consuming alcohol. Mothers who
      quit also reported allowing less smoking in the home. Relapse for quitters was
      highly correlated with partner's smoking. For women who cut down but did not
      quit, smoking level and age were most significant.

PMID- 7740012
TI  - The television, school, and family smoking prevention and cessation project.
      VIII. Student outcomes and mediating variables.
AB  - BACKGROUND: This paper presents the student outcomes of a large-scale, social
      influences-based, school and media-based tobacco use prevention and cessation
      project in Southern California. METHODS: The study provided an experimental
      comparison of classroom delivery with television delivery and the combination of
      the two in a 2 x 2 plus 1 design. Schools were randomly assigned to conditions.
      Control groups included "treatment as usual" and an "attention control" with the
      same outcome expectancies as the treatment conditions. Students were surveyed
      twice in grade 7 and once in each of grades 8 and 9. The interventions occurred
      during grade 7. RESULTS: We observed significant effects on mediating variables
      such as knowledge and prevalence estimates, and coping effort. The knowledge and
      prevalence estimates effects decayed partially but remained significant up to a 2
      year follow-up. The coping effort effect did not persist at follow-ups. There
      were significant main effects of both classroom training and TV programming on
      knowledge and prevalence estimates and significant interactions of classroom and
      TV programming on knowledge (negative), disapproval of parental smoking, and
      coping effort. There were no consistent program effects on refusal/self-efficacy,
      smoking intentions, or behavior. CONCLUSIONS: Previous reports demonstrated
      successful development and pilot testing of program components and measures and
      high acceptance of the program by students and parents. The lack of behavioral
      effects may have been the result of imperfect program implementation or low base
      rates of intentions and behavior.

PMID- 7740013
TI  - Prevention of HIV infection in drug abusers: a cost analysis.
AB  - BACKGROUND: Counseling and testing for HIV infection is performed at many sites,
      including drug treatment centers. The actual cost of providing HIV counseling and
      testing at drug treatment sites, based upon empirical data collection, has not
      been reported. The average lifetime medical cost for an HIV-infected individual
      is $56,000. This study provides both a systematic method for estimating HIV
      counseling and testing costs and actual cost results. These results can be
      compared with the medical costs associated with HIV infection. METHODS: At three
      publicly funded methadone treatment centers, we collected cost data on the
      provision of HIV counseling and testing. We obtained provider service times for
      HIV counseling and testing components, provider salaries and fringe rates,
      laboratory costs, and support costs at each center. RESULTS: The average cost of
      HIV counseling and testing is $215 per client entering HIV counseling and testing
      and $341 per client made aware of HIV serostatus. The total direct cost of
      providing HIV counseling and testing is $41 for an HIV-negative client who
      completes the process and $57 for an HIV-positive client; the support costs add
      an additional $175 per client. CONCLUSIONS: Existing methadone maintenance
      treatment clinics planning to add HIV counseling and testing can expect costs in
      a range of $189 to $242 per person entering HIV counseling and testing (1991
      dollars). Using an average lifetime cost of HIV infection ($56,000) and the
      average cost per person entering HIV counseling and testing ($215), if more than
      1 person in 260 changes his or her behavior to prevent one additional HIV
      infection, the ratio of medical care savings to costs of counseling and testing
      would be greater than 1.0, a cost-saving prevention strategy.

PMID- 7740014
TI  - Combined use of nicotine patch and gum in smoking cessation: a placebo-controlled
      clinical trial.
AB  - BACKGROUND: Smoking is considered as an addiction to nicotine for most subjects
      consuming 10 cigarettes or more per day. Hence, nicotine replacement therapy by
      way of gum, patch, or spray has been advocated. The rationale of this study is to
      evaluate the possible beneficial effects of adding nicotine gum to the routine of
      subjects using the nicotine patch. The effect of the nicotine patch against the
      placebo, both groups receiving placebo nicotine gum, has also been assessed.
      METHODS: Healthy subjects (374) were randomized at their work-setting in a 1-year
      double-blind placebo-controlled trial: 149 subjects to active nicotine patch +
      active gum (group 1), 150 to active nicotine patch + placebo gum (group 2), and
      75 to placebo patch + gum (group 3). Treatment duration was 12 weeks with a 16-hr
      transdermal patch of 15 mg, followed by a 6 + 6-weeks weaning period on
      respectively 10 and 5 mg patches. Gum use was not restricted during the first 6
      months, with recommendations to use at least four pieces a day. A strict
      definition of smoking abstinence was used in this study, which did not allow
      smoking any cigarette after Week 1. Nonsmoking status at each visit, as reported
      by the subjects, was verified by CO below 10 ppm in expired air. RESULTS:
      Abstinence rates in group 1 against group 2 were 34.2 and 22.7% (P = 0.027) at 12
      weeks, 27.5 and 15.3% (P = 0.010) at 24 weeks, and 18.1 and 12.7% (P = 0.191) at
      52 weeks. In group 3, abstinence rates were 17.3, 14.7, and 13.3% respectively at
      12, 24, and 52 weeks. Using logistic regression with adjustment for six baseline
      covariates, odds ratios for abstinence (with 95% CI) were computed. For group
      1/group 2, OR at 12, 24, and 52 weeks were 1.72 (1.03-2.94) (P = 0.039), 2.04
      (1.14-3.57) (P = 0.018), and 1.47 (0.76-2.76) (P = 0.125). No significant
      differences in OR were observed when comparing groups 2 and 3. Time to relapse is
      significantly longer in group 1 as compared to that of group 2 (P = 0.041),
      whereas no significant differences between groups 2 and 3 were observed. No
      significant differences between the three groups in systemic and local adverse
      drug events were observed. CONCLUSION: Adding active gum use to active patch use
      in subjects smoking 10 cigarettes or more a day increased abstinence rates, which
      are statistically significant up to 24 weeks.

PMID- 7740015
TI  - The relationship of active and passive smoking to carotid atherosclerosis 12-14
      years later.
AB  - BACKGROUND: Active and passive smoking have been found to be associated with
      clinical atherosclerotic disease. To explore the effects of smoking on
      atherogenesis, we investigated the relationship of past and current active and
      passive smoking to carotid atherosclerosis in middle-aged adults. METHODS: The
      study population consisted of 2,073 middle-aged residents of Washington County,
      Maryland. Information on active smoking and exposure to environmental tobacco
      smoke (ETS) was obtained from a 1975 census and from the baseline visit of the
      Atherosclerosis Risk in Communities (ARIC) Study in 1987-1989. Carotid artery
      intimal-medial wall thickness, measured by B-mode ultrasound methods in 1987
      1989, was used as an indicator of carotid atherosclerosis. Mean intimal-medial
      wall thickness (IMT) was adjusted for age, gender, cardiovascular risk factors,
      and education using multiple linear regression. RESULTS: The lowest mean IMT was
      found among never smokers who had never been exposed to ETS (mean +/- standard
      error: 0.706 +/- 0.013 mm). Exposure to ETS in one or both time periods was
      associated with increased IMT among never smokers (ETS in 1975 only: 0.731 +/-
      0.022; ETS in 1987-1989 only: 0.738 +/- 0.011; ETS in both periods: 0.734 +/-
      0.012). Active smoking in 1975 was also associated with increased IMT. The
      greatest mean intimal-medial wall thickness was found among persons who were
      current smokers in both time periods (0.807 +/- 0.009). CONCLUSIONS: Both past
      and current passive and active smoking are associated with increased carotid
      intimal-medial wall thickness.

PMID- 7740016
TI  - Need to smoke in the context of workplace smoking bans.
AB  - BACKGROUND: Workplace smoking bans are now widespread in a number of countries
      and are generally well accepted by smokers. Little is known about smokers who do
      not cope well with smoking bans. METHOD: A survey of 669 smokers was conducted 2
      years after the introduction of a workplace smoking ban. Variables associated
      with four different levels of need to smoke were examined. RESULTS: Nine percent
      reported experiencing a strong need to smoke at work, 26% a mild need, 45%
      occasional need, and 19% reported no need. Stronger need was related to (P <
      0.01): an index of addiction (higher daily smoking rates and fewer minutes to
      first cigarette of the day), violating smoking bans, going outside to smoke more,
      reducing consumption less since the bans, being less approving of the ban, and
      seeing it as inconvenient, seeing smoking as having less disadvantages (cons) and
      more advantages (pros), being less ready to quit, lower in confidence of
      quitting, and having less intention to quit. All of the above effects persisted
      after controlling for addiction, and the index of addiction only had independent
      relationships with going outside to smoke, reducing consumption less since the
      bans, higher pros of smoking and lower self-efficacy (P < 0.01). CONCLUSIONS:
      There is a small subgroup of smokers who have not adapted well to workplace
      smoking bans, as well as the much larger subset who report less difficulty. While
      nicotine addiction plays a role in perceived need to smoke, a number of
      potentially changeable cognitive characteristics were independently related to
      need. Workplace smoking policies and programs could take such characteristics
      into account in addressing the problems these smokers face.

PMID- 7740017
TI  - Evaluation of a Dutch community-based smoking cessation intervention.
AB  - BACKGROUND: Until 1990, smoking cessation interventions in the Netherlands were
      limited. The utility and effectiveness of community-based smoking cessation
      programs have not been examined. METHODS: In a treatment city (Den Bosch) a
      multicomponent community-based smoking cessation intervention was implemented in
      which local mass media and general practitioners draw smokers' attention to a
      local quit line. Telephone counselors advised applicants on their choice between
      self-help and group treatment and optional telephone counseling. Another Dutch
      city (Apeldoorn) served as a control. Population samples of smokers (n = 547 and
      n = 546) were interviewed three times at approximately 7-month intervals. Self
      help manual requesters (n = 84) and group participants (n = 83) were interviewed
      before and 6 months after treatment. RESULTS: Treatment modalities were
      successful; 13% of self-help manual requesters and 22% of group participants were
      abstinent after 6 months. On a population level the intervention resulted in
      significantly higher recall of self-help manual and group program in the
      treatment city. A modest intervention effect on prevalence of abstinence was
      found at the community level. CONCLUSIONS: Treatment modalities were effective
      within their participants, but the intervention effectiveness on a community
      level was limited. No significant difference was found between quit rates after
      14 months (7% in treatment city and 9% in control city). Several system failures
      could be identified. However, probably the intervention effect was seriously
      confounded by two national governmental publicity campaigns introducing and
      reinforcing a mandatory smoking ban and a series of national campaigns initiated
      by the united Dutch tobacco producers opposing the ban.

PMID- 7740018
TI  - Evaluating community-based nutrition programs: comparing grocery store and
      individual-level survey measures of program impact.
AB  - BACKGROUND: This paper examines whether an "environmental indicator"--a survey of
      grocery store product displays--can provide a realistic alternative to individual
      level telephone surveys for the evaluation of community-based nutrition programs.
      METHODS: Telephone and grocery store measures were used separately to evaluate
      three community-level dietary interventions that were part of the Kaiser Family
      Foundation Community Health Promotion Grants Program (CHPGP). Both surveys were
      conducted in the three intervention and seven control communities at three points
      in time: 1988, 1990, and 1992. The grocery store survey recorded the relative
      availability of low-fat and high-fiber products and the amount of store-provided
      health-education information. Self-reported dietary intake of residents was
      obtained in the same communities using a telephone survey. RESULTS: In the one
      community in which the intervention seemed to have contributed to reduced fat
      consumption, the grocery store and telephone surveys showed very similar relative
      changes for the only variable they had in common, low-fat milk consumption. In
      another community, both survey approaches indicated that there was no change or
      perhaps a slight worsening in the treatment relative to the controls. The third
      community produced the only contradictory results: the telephone survey suggested
      no change or perhaps a worsening, while the grocery store results were generally
      positive, though not statistically significant. CONCLUSION: These results,
      combined with the much lower cost of the grocery store survey, justify further
      pursuit of environmental indicators as an evaluation tool.

PMID- 7740019
TI  - Low-rate smokers.
AB  - BACKGROUND: Some smokers maintain a low daily smoking rate and do not appear to
      be addicted to nicotine (tobacco "chippers"). In a context of increasing social
      and environmental constraints on cigarette smoking, it is of interest to
      determine the population prevalence and the characteristics of low-rate smoking
      behavior. METHODS: A representative population survey was used to determine the
      prevalence and the correlates of low-rate smoking (five or less cigarettes a
      day). A range of sociodemographic, contextual, cognitive, and smoking-behavior
      variables was examined. RESULTS: Of 697 smokers age 20 years and over who had
      smoked for more than 2 years, 8.2% smoked five or less cigarettes a day; their
      average age was 39 years, and half were under 35 years of age; 88% had been
      smoking for 6 or more years; 86% were in the contemplation or preparation stages
      of readiness to quit. The significant independent predictors of being a low-rate
      smoker, compared to smoking at a higher daily rate, were perceiving quitting as
      not very difficult, smoking the first cigarette of the day more than 30 min after
      walking, buying packets of 30 or less cigarettes, and having not been advised by
      a doctor to quit. CONCLUSIONS: There were few differences between low-rate and
      other smokers on the range of variables that we were able to assess in a
      population survey. Since there is no safe level of cigarette smoking, medical
      advice to quit and public-education campaigns could target low-rate smokers
      specifically. Such initiatives could make significant contributions to reducing
      overall smoking prevalence.

PMID- 7740020
TI  - Establishment of an occupational diseases surveillance system to monitor blood
      lead levels in Taiwan.
AB  - BACKGROUND: Occupational diseases share many common characteristics with
      infectious diseases. However, the successful approach of using surveillance
      systems to eradicate infectious diseases has never been applied to the control
      and prevention of occupational diseases. METHODS: On the basis of a nationwide
      survey of blood lead levels in the general population in Taiwan, we (the Ministry
      of Health, Taiwan) have developed an obligatory surveillance system for blood
      lead. RESULTS: This government-administered system, which uses laboratory data as
      its source of information, enrolls all workers whose blood lead level exceeds
      regulation points (40 microgram/dl for men and 30 micrograms/dl for women). A
      Group of Health Promotion of Lead-using Workers (GHPLW) has been organized to be
      responsible for conducting epidemiological investigations to locate exposure
      sources in the workplace and to improve the working environment of cases and
      other workers with the same exposure. CONCLUSIONS: We emphasize that the
      accomplishment of the GHPLW's task depends not only on "curing" the case, but
      also on eradicating the lead exposure source and decreasing the blood lead level
      of workers in the workplace during long-term follow-up. The system aims to
      upgrade occupational disease control to the stage of specific prevention and
      health promotion. The establishment of this system is a historic step in
      industrial hygiene and occupational disease prevention in Taiwan.

PMID- 7740021
TI  - A controlled evaluation of a fitness and nutrition intervention program on
      cardiovascular health in 10- to 12-year-old children.
AB  - BACKGROUND: Programs to improve cardiovascular health in schoolchildren need
      careful scientific evaluation. METHOD: In a randomized controlled trial of
      nutrition and fitness programs over a period of about 9 months, 1,147 10- to 12
      year-olds from 30 schools were allocated to one of five health programs: fitness,
      fitness + school nutrition, school-based nutrition, school + home nutrition, home
      based nutrition, or a control group. Nutrient intake, fitness, anthropometry,
      blood pressure, and blood cholesterol were measured before and after
      intervention. RESULTS: Fitness increased and diastolic blood pressure and triceps
      skinfolds decreased significantly for girls in the fitness groups. Baseline
      consumption of sugar, fat, and fiber was outside national guidelines; blood
      cholesterol exceeded recommendations in one-third of children. In girls, fat
      intake decreased significantly in the two home nutrition groups and fiber intake
      increased in the school + home nutrition and fitness groups. Boys in the fitness,
      fitness + school nutrition, and school + home nutrition group reduced sugar
      intake. Change in sugar intake correlated negatively with change in fat intake in
      both boys and girls. CONCLUSIONS: Teacher-implemented health packages are
      feasible with minimal training but programs should differ between boys and girls.
      Fitness programs were more successful than nutrition education particularly in
      girls. Clearer nutrition messages should prevent reciprocal changes in sugar and
      fat. For girls, the 3 mm Hg reduction of diastolic blood pressure, less obesity,
      and increased fitness could translate into a substantial reduction in
      cardiovascular risk in adult life.

PMID- 7740022
TI  - [Immunoenzyme analysis based on laccase conjugates with fluorometric detection of
      the enzymatic reaction product].
AB  - The possibility of using homovanillic acid as a substrate of laccase (produced by
      the basidiomycete Coryolus hirsutus) has been demonstrated for the first time.
      The reaction was shown to result in the formation of a fluorescent product.
      Several kinetic parameters and optimal conditions were determined for this
      enzymatic reaction. The use of homovanillic acid as the substrate was found to
      increase the enzyme immunoassay sensitivity by an order of magnitude, compared to
      conventional substrates.

PMID- 7740023
TI  - [Solid-phase methods of immunoenzyme analysis of the herbicides simazine and
      atrazine].
AB  - Competitive methods of enzyme immuno assay (EIA) for detecting simazine and
      atrazine were developed, and conditions providing optimal performance were found.
      EIA sensitivity was shown to increase by an order of magnitude if samples were
      preincubated with antibodies; chloride ions were omitted; a herbicide-peroxidase
      conjugate was treated with urea. In EIA using labelled antibodies sensitivities
      thresholds towards simazine and atrazine were 0.05 and 0.1 ng/ml, respectively.
      EIA took 1-2 h to be done. The methods developed might be applied for quality
      control of water.

PMID- 7740024
TI  - [Can parameters of amperometric single-enzyme sensors be assessed using the
      concentration dependence of their response?].
AB  - The mathematical models of amperometric biosensors, with single- or two-substrate
      reaction occurring in their cover, were developed. A linear two-parametric
      equation of steady state was suggested for the biosensor detecting the product of
      single-substrate reaction corresponding to the Michaelis-Menten scheme. The
      conditions of equation applicability to description of standard biosensor
      kinetics in the wide range of substrate concentration, diffusion-module values,
      and permeability coefficients of three-layer-cover components were studied.

PMID- 7740025
TI  - [Yeast mitochondria: distinguishing features, and contribution to solving the
      general problems of bioenergetics. (Review)].
AB  - The data obtained by the author during more than 30 years of studies of yeast
      energy metabolism at cellular and mitochondrial levels are summarized. The data
      suggest that tightly coupled yeast mitochondria represent not only a fully
      functional, but often a preferable model system for studying many problems of
      bioenergetics.

PMID- 7740026
TI  - [Rates of physical development as a marker of the quality of metabolic control in
      children and adolescents with diabetes mellitus].
AB  - Physical development of 710 children and adolescents with insulin-dependent
      diabetes mellitus (IDDM) was studied over time. The patients were divided into 3
      groups: with growth rate above the 25th percentile of the age norm, with growth
      rate below the 10th percentile of the norm, and with growth rates between the
      10th and 25th percentiles of age norm. Analysis showed that (a) the presence of
      manifest decompensation (HbA1) higher than 12%, frequent ketoacidosis episodes is
      a factor of high risk of reduction of physical development rate in children and
      adolescents with IDDM; (b) the mean statistical rates of diabetic adolescents
      growth are characterized by delayed (by 1 to 2 years vs. the norm) pubertal
      growth "skip", and this growth skip in the patients is more levelled and
      stretched in time, and in some cases is virtually nor manifest; (c) if good
      compensation is attained and maintained after previous prolonged decompensation,
      compensating growth rates may develop in patients of both sexes both in childhood
      and adolescence.

PMID- 7740027
TI  - [Status of the sympatho-adrenal system in patients with diabetes mellitus:
      dependence on the course of the disease and the presence of late complications].
AB  - Blood plasma concentrations of noradrenaline, dopamine, serotonin and their
      metabolites (DOPAC, HVA, 5HIAA) were measured in 28 patients with insulin
      dependent and 32 with noninsulin-dependent diabetes mellitus (IDDM and NIDDM,
      respectively). The patients were divided into 4 groups. Group 1 were 15 patients
      without late diabetic complications, group 2 were 15 subjects with diabetic
      neuropathy, group 3 were patients with neuropathy and retinopathy (n = 16), and
      group 4 were 14 patients with neuropathy, retinopathy, and nephropathy. The
      results showed an increase of serotonin levels in IDDM patients vs. those with
      NIDDM, a positive correlation between serotonin and blood glucose levels in IDDM,
      increased concentration of dopamine and reduced plasma level of noradrenaline in
      patients with diabetic neuropathy vs. those without late diabetic complications.
      Plasma levels of dopamine were decreased in all the patients microvascular
      involvement. The findings indicate the development of changes in the
      sympathoadrenal system of patients with late diabetic vascular complications.

PMID- 7740028
TI  - [Taste perception in children with diabetes mellitus].
AB  - Gustatory perception was studied in 10 children aged 8 to 15 suffering from
      medium-severe diabetes mellitus by the functional mobility method. Glycemia
      values and the level of mobilization of gustatory lingual papillae were high when
      the patients were admitted; the characteristic reverse proportional relationship
      between these values, observed in healthy children, was absent. A course of
      therapy resulted in reduction of glycemia level, but the level of mobilization of
      gustatory papillae on an empty stomach was unchanged, the gastro-lingual reflex
      did not recover. The defected dissociation between glycemia values and the level
      of mobilization of the gustatory receptor system may be an extra for the
      diagnosis of diabetes severity and treatment efficacy.

PMID- 7740029
TI  - [Determination of fructosamine in the early diagnosis of disorders of
      carbohydrate metabolism].
AB  - Blood serum fructosamine level were measured on an empty stomach in 97 normal
      subjects and subjects with various disorders of carbohydrate metabolism (the so
      called "pre-diabetes" and changed glucose tolerance) in order to elucidate the
      significance of this factor as a marker of such disorders. Fructosamine
      concentrations were for the first time measured in children whose parents
      suffered from insulin-dependent or noninsulin-dependent diabetes mellitus. The
      content of fructosamine on an empty stomach was found to depend on the degree of
      carbohydrate metabolism disorders, increasing with the progress of these
      disorders. The findings permit a conclusion on the possibility of using
      fructosamine as a marker for the diagnosis of "pre-diabetes" in subjects with its
      levels of 2.5 to 2.99 mmol/l and of disordered glucose tolerance in those with
      its levels over 3 mmol/l and glucose level on an empty stomach no more than 6
      mmol/l.

PMID- 7740030
TI  - [Use of laser doppler flowmeter for the early diagnosis of diabetic
      microangiopathies].
AB  - Use of laser doppler flowmeter helped reveal in patients with diabetes mellitus a
      decrease of volumetric bloodstream in the capillaries of skin in the absence of
      clinical and biochemical evidence of microcirculatory disorders. Bloodstream
      parameters were correlated to the findings of objective methods of diagnosis at
      the stage of manifest clinical signs of vascular involvement of various
      localizations. Laser doppler flowmeter may be used for preclinical diagnosis of
      renal and ophthalmic involvement in diabetics with types I and II conditions as a
      method to monitor the therapy efficacy in patients with apparent clinical signs
      of microangiopathies. We should like to emphasize the possibility of mass
      screenings of patients and the simple technique of using the device, as well as
      the possibility of assessing the bloodstream not only in the skin, but in the
      organs and retina as well.

PMID- 7740031
TI  - [The lipid transport system and its hormonal regulators in youths suffering from
      obesity].
AB  - The type and degree of changes in the lipid transporting system of blood plasma
      and levels of hormonal provision of the regulatory processes in juvenile obesity
      of different degrees were under study. A single fat food loading was used to
      detect the precursors or latent forms of disorders in lipoprotein spectrum and
      their hormone regulators. A total of 35 obese patients aged 16 to 18 and 30 age
      matched healthy youths were examined. Analysis of the baseline values showed
      increased levels of apolipoprotein B, cholesterol, triglycerides, insulin, and
      reduced levels of apolipoprotein A1, high-density lipoprotein cholesterol in
      obese youths vs. controls. A atherogenic pattern of changes in the lipoprotein
      and apolipoprotein spectra of the plasma obese youths was clearly seen under
      conditions of fat food loading, these changes being associated with disordered
      insulin reaction to intake if exogenous fat. The examinees suffering from obesity
      a varying degree, mainly from the abdominal variant, presented with a complex of
      interrelated metabolic disorders (hyperinsulinemia, insulin resistance,
      dyslipoproteinemias),--the metabolic X syndrome, this referring them to a group
      at risk of developing atherosclerosis, essential hypertension, diabetes mellitus
      irrespective of the degree of general obesity.

PMID- 7740032
TI  - [An attempt to use enalapril in arterial hypertension in patients with juvenile
      obesity].
AB  - Clinical efficacy of enalapril, a drug belonging to a group of angiotensin
      converting enzyme inhibitors, was studied in patients with pubertal juvenile
      dyspituitarism (juvenile obesity) coursing with arterial hypertension. A reactive
      increase of plasma renin activity and reduced concentration of plasma aldosterone
      were revealed. The drug was characterized by a pronounced hypotensive effect. No
      negative effects on the blood lipid spectrum or carbohydrate metabolism were
      observed. The study showed that enalapril may be a drug of choice in the
      treatment of the hypertensive syndrome in patients with juvenile obesity.

PMID- 7740033
TI  - [Role of non-specific cerebral systems in the pathogenesis of thyroid gland
      diseases].
AB  - Ten patients with diffuse toxic goiter, 1-2 nd degree, ten ones with hypothyrosis
      of medium severity, and a group of healthy controls were examined. Manifest
      emotional, personality, and vegetative disorders were revealed in patients of
      both groups, as well as changes in the electrical activity of the brain and in
      status of the afferent systems of the brain, this being indicative of marked
      dysfunction of nonspecific cerebral systems in patients with thyroid diseases.
      Anxiety depressive emotional disorders and activation of the in-depth
      compartments of the membranous reticular complex were revealed in both groups of
      patients. These changes are nonspecific and appear to represent a common
      neurogenic mechanism of thyroid dysfunction. General activation of the brain and
      peripheral cerebral activation detected in patients with hyperthyroidism are
      secondary and result from effects of thyroid hormones on the nervous system.

PMID- 7740034
TI  - [Attempt to use the genetically engineered growth hormone SAIZEN in children with
      somatotropic insufficiency: results of clinical trials in Russia].
AB  - The efficacy and safety of SAISEN, a recombinant human growth hormone obtained
      from mammalian cells, was tested in children with hypophyseal nanism. The
      treatment duration was 1 year. The results indicate that SAISEN (ARES-SERONO) is
      a highly effective and safe preparation of growth hormone, noticeably stimulating
      the growth rate both in previously untreated children with somatotropic
      insufficiency, and in those previously treated with STH preparations. Therapy
      with SAISEN was not associated with any side effects, as shown by both clinical
      and laboratory data.

PMID- 7740035
TI  - [Comprehensive ultrasound study in surgical diseases of the adrenals].
AB  - Combined staged ultrasonic examination of 53 patients with surgical diseases of
      the adrenals (Icenko--Cushing's disease and hormonally active tumors) included
      preoperative transcutaneous ultrasonic examination, ultrasound-monitored spot
      fine needle aspiration biopsy, intraoperative and postoperative ultrasonic
      examinations. Transcutaneous ultrasonic examination was found to be little
      informative in Icenko--Cushing's disease, whereas in adrenal tumors it was
      virtually as sensitive as computer-aided tomography. Ultrasound-monitored spot
      fine needle aspiration biopsy proved to be a highly informative safe method,
      which helps morphologically diagnose the disease before surgery. Intraoperative
      ultrasonic examination helped reduce the surgical trauma in all the cases, and in
      patients with Icenko--Cushing's disease it gave an idea of the type of
      morphologic changes in the removed adrenal. Ultrasonic monitoring of tissue
      status at the site of intervention helped timely detect the postoperative
      complications.

PMID- 7740036
TI  - [Planning and practice of clinical research: basic principles and errors as
      exemplified by Russian diabetology. A lecture].

PMID- 7740037
TI  - [Assistance for patients with thyroid gland diseases (lecture)].

PMID- 7740038
TI  - [Characterization of pancreatic beta cell receptors binding sulfanilamide drugs].
AB  - Analysis of pancreatic beta-cell receptors binding the sulfanilamide drugs widely
      used in therapy of type II diabetes, such as glibenclamide, glipizide, and
      gliclazide, showed that these drugs are characterized by excellent parameters of
      specific binding to these receptors. The receptors were tested for two
      parameters: number of binding sites and dissociation constant. Glibenclamide was
      the most active of the drugs we tested, the other two agents being less active.
      Binding of these agents was reversible. The problem of identification of the
      examined receptors of sulfanilamides with K(+)-ATP-sensitive channels, similarly
      active conductors of the information transported by the sulfanilamide drugs in
      the mechanism of insulin secretion, is discussed.

PMID- 7740039
TI  - [Dynamics of a series of parameters of cellular and humoral immunity in patients
      with diabetes mellitus type I].
AB  - Fifty-two patients with type I diabetes mellitus were examined. The patients were
      divided into 4 groups with various duration of the disease: group 1 included
      patients with the newly diagnosed disease, group 2 those with disease standing of
      1 to 5 years, group 3 were patients suffering from diabetes for 6 to 10 years,
      and group 4 were diabetics for 10 years and more. The parameters examined were
      antibodies to surface antigens of islet cells, absolute and relative counts of T
      and B lymphocytes in the peripheral blood, counts of T- helpers and T-suppressors
      and cytotoxic cells and their ratios, counts of natural killers, DR (+) and JgG
      (+) cells, and basal C-peptide level. The results showed a correlation between
      autoantibodies to surface antigens of islet cells and the count of B lymphocytes,
      an inversion of T lymphocyte subpopulations, with the helper/suppressor index
      increased at the initial stages of the disease and decreasing with the disease
      progress.

PMID- 7740040
TI  - [Functional state of the thyroid gland in rats receiving an increased quantity of
      iodine with drinking water].
AB  - Thyroid and adrenocortical function was examined in rats fed increasing
      quantities of iodine with drinking water. No noticeable deviations in thyroid
      hormone levels were found in the blood of experimental animals. Thyroid hormone
      levels in thyroid tissue were changing in the same direction in the animals kept
      on various iodine diets, these changes depending on experiment duration: an
      increase of thyroxine and more so, of triiodothyronine was observed in 50 days,
      and reduction thereof in 90 days. In rats fed the maximal iodine dose, 8000
      micrograms daily, the level of thyroglobulin in thyroid tissue decreased.
      Increased iodine consumption reduced the glucocorticoid function of the adrenals
      in experimental animals, as manifested by reduction of corticosterone levels in
      the adrenals, blood plasma, and reduction of nonmetabolized hormone excretion
      with the urine.

PMID- 7740041
TI  - [Effects of hypothalamic mediator systems on the hormonal changes in rabbit blood
      during prolonged electric stimulation of emotiogenic zones of the hypothalamus].
AB  - Changes in the blood hormonal levels were studied in 36 rabbits with electrodes
      implanted to the area of the dorsomedial nuclei of the hypothalamus in the course
      of a 5-cycle electrostimulation experiment. After each period blood hormonal
      levels were correlated to the activities of the hypothalamic catecholamine-, GABA
      , and serotoninergic systems. The first two cycles of the experiment were
      associated with a high activity of the hypothalamic mediator systems and with
      increased levels of all hormones in the blood. The functional activity of the
      hypothalamus was reduced due to the predominance of stress-limiting systems. The
      initial reduction of GABA, and then of serotonin in the hypothalamus caused be
      the end of experiment a reduction of the blood levels of the tested hormones,
      except the Ca-regulating ones and active renin. Disturbances in the regulatory
      mechanisms of hypothalamic mediator systems leads to an increase in its
      excitability and to transformation of the adaptive pattern of hormonal changes
      into pathological mechanisms of prolonged emotional stress.

PMID- 7740042
TI  - [Proteins binding thyroid hormones and their physiologic role].

PMID- 7740043
TI  - [Minidiab test to assess the functional state of pancreatic beta-cells in the
      children of diabetics].
AB  - The levels of glucose, insulin, and C-peptide in the blood serum were measured in
      38 subjects with normal and impaired glucose tolerance whose parents suffered
      from insulin-dependent and noninsulin-dependent diabetes mellitus (IDDM and
      NIDDM, respectively) and in 12 normal subjects without hereditary aggravation for
      diabetes mellitus in order to specify the peculiarities of development of
      diabetes mellitus of various types. Reliably increased levels of glucose,
      insulin, and C-peptide on an empty stomach and absence of adequate secretion of
      insulin and C-peptide in response to stimulation with 5 mg of minidiab, expressed
      by a later and less manifest release of insulin and C-peptide, were observed in
      the test group, in contrast to healthy controls. The detected changes augment
      with the progress of carbohydrate metabolism disorders, being more marked in the
      subjects whose parents suffered from IDDM. The findings permit a conclusion that
      function of the insular system is changed during early disorders of carbohydrate
      metabolism in subjects whose parents suffered from both forms of diabetes
      mellitus. Minidiab test is recommended to specify the function of the pancreatic
      insular system.

PMID- 7740045
TI  - Dictyostelium discoideum: cellular self-organization in an excitable biological
      medium.
AB  - The dynamics which govern the establishment of pattern and form in multicellular
      organisms remain a key problem of developmental biology. We study this question
      in the case of morphogenesis during aggregation of the slime mould Dictyostelium
      discoideum. Here detailed experimental information allows the formulation of a
      mechanistic model in which the central element is the coupling of the previously
      much-studied intracellular cyclic AMP signalling with the chemotactic cell
      response in cyclic AMP gradients. Numerical simulations of the model show
      quantitatively how signal relay, chemotactic movement and adaptation orchestrate
      the collective modes of cell signalling and migration in the aggregating cell
      layer. The interaction of chemotaxis with the cyclic AMP excitation waves causes
      the initially homogeneous cell layer to become unstable towards the formation of
      a branching cell stream pattern with close cell-cell contacts as observed in
      situ. The evolving cell morphology in turn leads to a pattern of non-homogeneous
      excitability of the medium and thus feeds back into the cAMP dynamics. This
      feedback can explain the decrease in signalling period and propagation speed with
      time, as well as observations on the structure of the spiral wave core in this
      self-organized excitable medium.

PMID- 7740044
TI  - A theory of tension fluctuations due to muscle cross-bridges.
AB  - We present an analytical theory for the spectrum of tension fluctuations due to
      muscle cross-bridges. The theory is based upon the Langevin theory of brownian
      motion, and is illustrated using a simplified three-state model for the cross
      bridge cycle, which is intended to model cross-bridges in fibrillar insect flight
      muscle. Langevin white-noise sources, representing fluctuations in the net
      transition rates for each step in the cycle, are introduced into the rate
      equations, and their strengths are adjusted to give the correct mean-square
      fluctuations in the occupation probabilities. The Langevin theory shows that the
      noise is closely related to the elastic properties of cross-bridges, and it also
      shows in detail how each step in the cross-bridge cycle contributes differently
      to the noise spectrum. We find that the total noise increases with filament
      displacement. For small filament displacements, the noise is dominated by the
      power stroke and by dissociation at the end of the cycle. These contributions
      increase in the region of stretch activation, whilst at larger displacements,
      where the cross-bridge becomes locked in the strong-binding state, the noise is
      much larger and is dominated by attachment and detachment at the beginning of the
      cycle. The cross-bridge properties in this regime are strongly affected by free
      inorganic phosphate. Finally, we show how the noise spectrum is modified by the
      inclusion of a series compliance representing a practical force transducer.

PMID- 7740046
TI  - Evidence that some dinoflagellates contain a ribulose-1,5-bisphosphate
      carboxylase/oxygenase related to that of the alpha-proteobacteria.
AB  - The ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit from
      several dinoflagellates has a structure similar to that of the Form II enzyme
      from Rhodospirillum and Rhodobacter species rather than the Form I Rubisco of
      eukaryotic algae and higher plants. The dinoflagellate Rubisco was identified on
      native polyacrylamide gels by autoradiographic detection of the stable Rubisco
      [2'-14C]-2-carboxy-D-arabinitol 1,5-bisphosphate complex. The antibody to the
      Symbiodinium sp. large subunit cross reacts with both the Rhodospirillum rubrum
      and Rhodobacter sphaeroides Form II enzyme whereas antibodies to the R. rubrum
      Rubisco cross react with a range of dinoflagellate Rubisco large subunits. The N
      terminal amino acid sequence of the large subunit from both Symbiodinium sp. and
      Amphidinium carterae confirmed this relation. The lack of inhibition of the
      dinoflagellate Rubisco by 6-phosphogluconate is consistent with this structure.

PMID- 7740047
TI  - The establishment of intracellular symbiosis in an ancestor of cockroaches and
      termites.
AB  - All cockroaches examined so far have been found to harbour a bacterial
      endosymbiont in specialized cells of the fat body, whereas Mastotermes
      darwiniensis is the only termite currently known to harbour an intracellular
      symbiont. The localization and mode of transmission of these bacteria are
      surprisingly similar, but so far no data have been published on their
      phylogenetic relationships. To address this issue, molecular sequence data were
      obtained from the genes encoding the small subunit ribosomal RNA of the M.
      darwiniensis endosymbiont, and compared with those obtained from endosymbionts of
      seven species of cockroaches. Molecular phylogenetic analysis unambiguously
      placed all these bacteria among the flavobacteria-bacteroides, indicating that
      the endosymbiont of M. darwiniensis is the sister group to the cockroach
      endosymbionts examined. Additionally, nucleotide divergence between the
      endosymbionts appears to be congruent with the palaeontological data on the
      hosts's evolution. These results support previous claims that the original
      infection occurred in an ancestor common to cockroaches and termites. A loss of
      endosymbionts should subsequently have occurred in all termite lineages, except
      that which gave rise to M. darwiniensis.

PMID- 7740048
TI  - Phylogenetic evidence for the role of a pre-existing bias in sexual selection.
AB  - Females of the genus Xiphophorus, which includes unsworded platyfish and sworded
      swordtails, share a mating preference which favours a sword despite phylogenetic
      evidence that the sword was not present in the evolutionary history of platyfish.
      A recent molecular phylogeny, however, proposes that the platyfish arose from
      within the swordtails. If this is the case, the preference for a sword in
      platyfish may be a retained ancestral preference rather than a bias that evolved
      before the first appearance of the sword. To determine whether or not the
      preference favouring a sword is an ancestral bias present before the evolution of
      the sword, I tested sword preferences in the sister genus, Priapella, which lacks
      a sword: female P. olmecae were found to prefer conspecific males with artificial
      swords to those without swords. These results suggest that a pre-existing bias
      favouring a sword arose before the divergence of these two genera, and thus
      before the appearance of a sword. In addition, the strength of the preference
      exhibited by P. olmecae females for a sword was found to vary with sword length;
      as the length of the sword was increased, the strength of the preference
      increased. Female P. olmecae, therefore, prefer males with longer swords to males
      with shorter swords. This increasing preference with sword length is similar to
      the preference of green swordtails, suggesting that the preference has a common
      basis in the two groups. More generally, this work further establishes the pre
      existing bias model as a viable explanation for the evolution of female
      preferences and male traits.

PMID- 7740049
TI  - Evidence for insertion of a new intron into an Mhc gene of perch-like fish.
AB  - The evolution of the major histocompatibility complex (Mhc) has been studied to
      understand the origin of the immune system, of which it constitutes an essential
      part. In the present study, the Mhc is used to shed light on questions regarding
      the origin of introns and the phylogeny of fishes. The organization of the coding
      (exon) and non-coding (intron) regions of both class I and class II major
      histocompatibility complex (Mhc) genes is highly conserved in all vertebrate
      classes; the only variation observed until now is in the number of exons encoding
      the membrane-anchoring part. Moreover, there is a good correspondence between the
      exon-intron organization at the DNA level and the division into structurally and
      functionally defined domains at the protein level. Here we describe the first
      major exception to this uniformity. The immunoglobulin-like domain of the class
      II beta-chains in perch-like fishes (Percomorpha) is not encoded in one exon, as
      it is in all other vertebrates studied thus far, but in two exons. The length of
      the extra intron varies from gene to gene and from species to species, but is
      generally less than 200 base pairs (b.p.). Only one of the sequenced introns is
      about 500 b.p. long. In some of the genes, the intron contains a hexamer repeat.
      The repeat is present in the transcript at the site at which the intron
      interrupts exon 3 in the genomic DNA. The intron may therefore have arisen by
      repeated tandem duplication of this sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740050
TI  - CCKA, but not CCKB, agonists suppress the hyperlocomotion induced by endogenous
      enkephalins, protected from enzymatic degradation by systemic RB 101.
AB  - Interactions between CCKergic and enkephalinergic systems were studied in mice
      using behavioral responses measured in Animex. The hyperlocomotion induced by 5
      mg/kg of RB 101, a mixed inhibitor of enkephalin-degrading enzymes able to cross
      the blood-brain barrier, was previously shown to be mediated by delta-opioid
      receptor stimulation. The IP administration of a CCKA agonist, Boc-Tyr-Lys-(CONH
      o-tolyl)-Asp-Phe-NH2 (0.1, 1, 10 micrograms/kg), suppressed the hyperlocomotion
      produced by IV injection of 5 mg/kg of RB 101. The effect of the CCKA agonist was
      suppressed by a selective CCKA antagonist, devazepide, injected IP at doses of 20
      and 200 micrograms/kg and was potentiated by the selective delta-opioid
      antagonist naltrindole at the doses of 0.03 mg/kg. IP injection of the selective
      CCKB agonist BC 264 (0.1-1 mg/kg) did not modify the RB 101-induced
      hyperlocomotor effect. These results reinforce the observed physiological
      antagonism between the endogenous CCK and opioid systems but are at variance with
      the responses measured in stressful conditions. It is concluded that CCKA, but
      not CCKB, receptor activation counteracts the opioid-related hyperlocomotion.

PMID- 7740051
TI  - IL-1 beta and TNF alpha modulate delta 9-tetrahydrocannabinol-induced catalepsy
      in mice.
AB  - The role of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha),
      interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor
      alpha (TNF alpha) in THC-induced catalepsy in mice was examined. Recombinant IL-1
      beta (400 ng/mouse, IV) and TNF alpha (500 ng/mouse, IV) were effective in
      potentiating the cataleptic effect of low-dose THC (10 micrograms/mouse, IV).
      Recombinant IL-1 alpha and IL-6 did not potentiate catalepsy at any dose tested.
      Anti-IL-1 beta and anti-TNF alpha antibodies were effective in attenuating high
      dose (75 micrograms/mouse) THC-induced catalepsy. Antibodies to IL-1 alpha and IL
      6 had no effect on catalepsy. Early onset catalepsy (10 min postinjection) was
      potentiated by exogenous recombinant IL-1 beta and TNF alpha but only later
      catalepsy (2 h postinjection) was attenuated by antibodies to endogenous IL-1
      beta or TNF alpha. This divergence of the cytokine effect suggests that these
      substances regulate, by different mechanisms, the early and late THC-induced
      cataleptic response.

PMID- 7740052
TI  - Crucial role of D1 dopamine receptors in mediating the antidepressant effect of
      imipramine.
AB  - Although the neurochemical effects of chronic imipramine (IMI) treatment have
      been related to an increased adrenergic as well as dopaminergic transmission, no
      clear-cut evidence exists on whether one of these two neuronal systems mediates
      the behavioral effects of the tricyclic compound. Because a large body of
      evidence favors the role of dopamine, the interference of a selective inhibition
      of D1 or D2/D3 dopamine receptors on IMI effect upon the learned helplessness
      behavior (LH) in rats was studied. A 2-week treatment with SCH 23390, followed by
      a 24-h washout, showed almost the same efficacy as chronic IMI in preventing LH
      induction. Moreover, SCH 23390 given acutely before the pretest completely
      antagonized the effect of chronic IMI. Furthermore, SKF 38393 administered to
      drug-naive animals prior to the unavoidable shocks completely neutralized its
      behavioral sequelae. Finally, the inhibition of D2/D3 dopamine receptors by acute
      sulpiride did not modify IMI efficacy. These results strongly suggest that D1
      dopamine receptor function controls the reactivity of animals exposed to a
      prolonged unavoidable stress, and mediates IMI antidepressant effect.

PMID- 7740053
TI  - D2 receptors in the ventrolateral striatum are involved in feeding behavior in
      rats.
AB  - To study the role of dopamine D1 and D2 receptors in the ventrolateral striatum
      in feeding behavior, a D1 receptor agonist (CY 208-243), a D1 receptor antagonist
      (SCH 23390), a D2 receptor agonist (quinpirole), and a D2 receptor antagonist [(
      )-sulpiride] were perfused via a microdialysis probe into the ventrolateral
      striatum of rats fasted for 22 h. Then the rats were allowed to feed freely for 6
      h. Sulpiride perfusion at a high concentration suppressed food and water intake
      significantly, whereas dopamine release and the levels of DOPAC and HVA were
      increased at all concentrations. In contrast, quinpirole perfusion at a high
      concentration increased food intake by 41%. Dopamine release and the levels of
      DOPAC and HVA were decreased at all concentrations. On the other hand, neither CY
      208-243 nor SCH 23390 changed food intake or dopamine release, but both drugs
      decreased water intake. These results suggest that D2 receptors in the
      ventrolateral striatum have a more important role than D1 receptors in the
      feeding behavior of rats.

PMID- 7740054
TI  - Locomotor stimulant effects of cocaine and novel cocaine analogs in DBA/2J and
      C57BL/6J inbred mice.
AB  - The current study compared the potencies of cocaine and a series of substituted
      phenyltropane analogs of cocaine in stimulating locomotor activity in two
      genetically distinct strains of mice previously shown to differ in their
      locomotor responsiveness to cocaine. In addition, these compounds were compared
      for their abilities to induce stereotyped behaviors in naive and cocaine
      pretreated mice. All of the analogs tested were more potent locomotor stimulants
      than cocaine in both strains. Interstrain differences in the locomotor stimulant
      efficacy of RTI-31 and RTI-98 parallel those of cocaine, with DBA/2J mice being
      stimulated to a greater extent than C57BL/6J mice at maximally active doses.
      Significant differences exist in the onset and duration of action among cocaine
      and several analogs. Whereas the action of cocaine peaks in the first 10 min
      after injection and thereafter rapidly declines, the stimulant effects of RTI-31,
      RTI-98, and RTI-113 are maximal at 30-40 min and remain consistent through 60 min
      postinjection. The current results are discussed in the context of previously
      published reports of genotype-dependent differences in behavioral responsiveness
      to cocaine in the DBA/2J and C57BL/6J strains.

PMID- 7740055
TI  - Reinforcing effects of triazolam in sedative abusers: correlation of drug liking
      and self-administration measures.
AB  - Six male subjects with histories of sedative abuse were allowed to orally self
      administer a maximum of 18 color-coded triazolam and placebo capsules during
      daily 3-h sessions. The schedule of reinforcement was a signaled fixed-interval
      10-min schedule in which triazolam and placebo were concurrently available as
      mutually exclusive choices. Triazolam was shown to be a reinforcer in four of the
      six subjects. The two subjects who did not self-administer triazolam in
      preference to placebo also had lesser histories of drug dependence. Self
      administration of triazolam (0.125 or 0.25 mg per capsule) was generally stable
      over 7-10 days. Manipulations of triazolam dose (0.0312-0.25 mg) per capsule in
      two subjects showed that the number of capsules self-administered was inversely
      related to capsule dose. Subject ratings of drug liking obtained from
      experimenter-administered doses of triazolam were correlated with self
      administration behavior occurring 1-7 days later. Of the subject ratings, next
      day ratings obtained on the day after dosing resulted in significant correlations
      whereas same day ratings obtained while subjects were under the influence of
      triazolam did not. These results have important implications for abuse liability
      prediction and suggest that next day ratings have greater predictive validity
      than measures collected while subjects are under the influence of
      benzodiazepines.

PMID- 7740056
TI  - Suppression of haloperidol-induced oral dyskinesias in rats by vigabatrin.
AB  - Acute and chronic administration of vigabatrin, a selective inactivator of GABA
      T, suppresses haloperidol-induced dyskinesias at low doses without preventing the
      enhancement of striatal dopamine D2 receptor density or the development of
      vacuous chewing movements. The long-term administration of vigabatrin does not
      attenuate its effect. The observations presented in this work support the GABA
      hypothesis of haloperidol-induced vacuous chewing behavior in rats, and suggest
      that vigabatrin is an appropriate means to enhance nigral GABAergic activity.

PMID- 7740057
TI  - Strain and age differences in acoustic startle responses and effects of nicotine
      in rats.
AB  - Two experiments examined the effects of age, genetic strain, and nicotine on
      acoustic startle response (ASR) amplitude and prepulse inhibition (PPI) in rats.
      ASR amplitude measures reactivity to external stimulation, and PPI is used as an
      index of sensory gating related to attention. Both ASR amplitude and PPI have
      been previously reported to be increased by nicotine in adult rats. Experiment 1
      examined effects of chronically administered nicotine and saline on ASR and PPI
      in Wistar, Long-Evans, and Sprague-Dawley rats (40 days of age). Experiment 2
      examined the effects of chronically administered nicotine and saline in Sprague
      Dawley rats of two age groups: 40 and 70 days of age at the beginning of the
      study. ASR amplitude differed significantly across strains with the values for
      Wistar > Sprague-Dawley > Long-Evans, and there were no differences in percent of
      PPI among the three strains. In addition, results of Experiment 2 indicated that
      older rats had significantly greater ASR amplitudes and PPI than younger rats.
      Consistent with previous reports, nicotine increased ASR and PPI in the older
      rats; however, there were no significant differences in the younger rats.
      Therefore, age and genetic strain are important variables in the analysis of
      nicotine's effects on startle behaviors in rats.

PMID- 7740058
TI  - Glycine enhances the central depressant properties of ethanol in mice.
AB  - The interaction between ethanol and glycine in the central nervous system was
      investigated in male Swiss-Webster mice. The loss of the righting reflex (LORR)
      was used as a measure of central nervous system depression. Mice were injected
      with ethanol (4.0 g/kg, IP), causing an ethanol-induced LORR. Immediately after
      the animals regained the righting reflex from ethanol administration, they
      received an intracerebroventricular (ICV) injection of saline or glycine (1, 15,
      25, or 50 mumol/kg) in a volume of 5 microliters. Upon ICV injection of glycine,
      the mice lost the righting reflex once again. This effect of glycine in the
      presence of ethanol occurred rapidly and in a dose-dependent manner. Glycine
      induced a return to the LORR of 12.6 +/- 0.7, 24.5 +/- 1.3, 32.8 +/- 2.0, and
      46.8 +/- 4.5 min when doses of 1, 15, 25, and 50 mumol/kg, respectively, were
      injected. D-Serine (15, 25, or 50 mumol/kg), an amino acid precursor of glycine,
      was injected (ICV) after the animals regained the righting reflex following
      ethanol injection (IP). Serine caused a return to the LORR of 0.5 +/- 0.5, 6.0 +/
      1.0, and 6.5 +/- 0.9 min when doses of 15, 25, and 50 mumol/kg, respectively,
      were injected. Strychnine was used to attenuate the ability of glycine and serine
      to cause a return to the LORR in the presence of ethanol. Strychnine, a
      competitive antagonist of glycine, significantly reduced the ability of glycine
      and serine to enhance the depressant action of ethanol.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7740059
TI  - Attenuating effect of bifemelane on an impairment of mealtime-associated activity
      rhythm in aged and MK-801-treated rats.
AB  - In the present experiment, we examined the attenuating effect of bifemelane
      hydrochloride (BF), 4-(o-benzyl phenoxy)-N-methylbutylamine hydrochloride, on the
      impairment of time perception caused by daily scheduled feeding using aged and MK
      801-treated rats. When feeding was restricted to a single meal at a fixed time of
      day (1300-1700 h) for six successive days, young rats exhibited intense locomotor
      activity 1-3 h before feeding time. Intense locomotor activity was observed for
      1200-1700 h even on the fasting day (day 7; mealtime-associated activity).
      Mealtime-associated activity was impaired in 24-mo-old rats and also in N-methyl
      D-aspartate receptor antagonist, MK-801-treated rats. Daily injections of
      bifemelane at 1700 h for six successive days significantly attenuated the
      impairment of mealtime-associated activity on the seventh day in a dose-dependent
      manner in aged rats. In addition, cotreatment of MK-801 with bifemelane blocked
      the MK-801-induced impairment of mealtime-associated activity. The present study
      suggests that bifemelane has an enhancing effect on learning and memory
      performance, such as spatial and temporal perception.

PMID- 7740060
TI  - Discriminative stimulus properties of the stereoisomers of the phosphodiesterase
      inhibitor rolipram.
AB  - The discriminative stimulus properties of the specific type IV phosphodiesterase
      inhibitor, rolipram, and its two stereoisomers were assessed using standard two
      lever drug discrimination procedures in which responding on the appropriate lever
      was reinforced on a FR10 schedule. In three separate drug cues based on training
      rats to discriminate the racemate (0.2 mg/kg, IP), the (-)-isomer (0.1 mg/kg), or
      the (+)-isomer (2 mg/kg) from vehicle, all forms substituted for one another,
      differing only in potency. In keeping with published reports, the (-)-isomer was
      the more potent form, the (+)-isomer being approximately 10 times less potent.
      Several phosphodiesterase (PDE) inhibitors were found to substitute for the
      racemate cue, their potencies in the behavioural measure correlating with their
      potency in displacing [3H]rolipram from its forebrain binding sites in vivo (r =
      0.95), suggesting that the discriminative stimulus depends on an action of the
      drug upon this site. Because rolipram has been reported to possess antidepressant
      activity, the ability of the tricyclic antidepressant imipramine to substitute
      for rolipram was investigated; doses of 10 and 20 mg/kg did not substitute.
      Amphetamine (0.156-1.25 mg/kg) also was inactive. Lisuride gave rise to drug
      appropriate responding in 50% of rats only at a dose of 0.078 mg/kg, which
      severely disrupted responding. It is concluded that the rolipram discriminative
      stimulus is dependent on the selective PDE inhibitory activity of the drug, and
      that it does not constitute a cue based on the antidepressant property of
      rolipram.

PMID- 7740061
TI  - Effects of propranolol and atenolol on immobilization stress-induced hypertension
      and down-regulation of central beta-adrenoceptors in rats.
AB  - Effects of chronic treatment with propranolol or atenolol on stress-induced
      changes in blood pressure, body weight, and cerebral beta-adrenoceptors in rats
      were examined and compared with the effects of chronic treatment with prazosin.
      Immobilization stress (2 h daily for 2 weeks) induced a moderate elevation of
      blood pressure, loss of body weight gain, and downregulation of cerebral beta
      adrenoceptors, but produced no changes in the cerebral alpha 1-adrenoceptors.
      Chronic administration of propranolol (5 or 50 mg.kg-1), atenolol (5 or 50 mg.kg
      1) or prazosin (2 or 20 mg.kg-1) inhibited stress-induced hypertension but did
      not affect loss of body weight gain. Propranolol increased the density of
      cerebral beta-adrenoceptors by 77% and reduced the downregulation induced by
      stress. Atenolol also increased the density of cerebral beta-adrenoceptors by 34%
      and abolished the stress-induced downregulation in cerebral beta-adrenoceptor
      density. In contrast, prazosin had no effect on the cerebral beta-adrenoceptors
      in nonstressed or stressed rats. These results suggest that the antihypertensive
      action of propranolol and atenolol may be partly associated with the inhibition
      of stress-activated central beta-adrenoceptor transmission.

PMID- 7740062
TI  - Switching to ultralow nicotine cigarettes: effects of different tar yields and
      blocking of olfactory cues.
AB  - Twelve female smokers smoked two of each of three types of cigarettes in three
      sessions. One cigarette was smoked with and the other one without nose blocking.
      Total puff volumes increased for ultralow tar/nicotine (tn) cigarettes as
      compared with habitual regular tar/nicotine (TN) cigarettes and regular
      tar/ultralow nicotine (Tn) cigarettes, as the result of an increase in the number
      of puffs. TN and tn, but not Tn cigarettes changed heart rate and beta-power in
      the electroencephalogram; all three reduced craving, although they differed
      considerably in subjective acceptance. Blocking of olfactory cues influenced
      respiration and reduced the average puff volumes, taste, and enjoyment, but it
      did not differentially affect any parameters among the TN, tn, and Tn cigarettes,
      which suggests that olfaction plays a minor role in regulating puffing behavior.
      It was concluded that as compared with regular TN cigarettes, only the tn, but
      not the Tn cigarettes were oversmoked by about 35%, and that Tn cigarettes might
      be useful for assessing nonnicotinic factors in cigarette smoking.

PMID- 7740063
TI  - Effects of single and repeated electroconvulsive shock on isoproterenol
      stimulated pineal N-acetyltransferase activity and melatonin production in rats.
AB  - The response of the pineal gland to acute isoproterenol administration represents
      a useful tool to investigate beta 1-adrenoceptor function, because the production
      of melatonin and the activity of its main synthesizing enzyme, N
      acetyltransferase (NAT), are regulated by beta 1-adrenergic receptors. In the
      present study, rats underwent single electroconvulsive shock (ECS) administration
      (0.80 mA, 0.5 s, at midday), chronic ECS treatment (0.80 mA, 0.5 s, once daily
      for 8 days), or sham treatments. On the day after the last ECS or sham ECS,
      animals were injected with isoproterenol hydrochloride (1 mg.kg-1 SC) or volume
      matched saline at 1600 h. After single ECS, isoproterenol injection induced a
      clear-cut increase in both pineal NAT activity and melatonin levels with no
      significant differences between ECS-treated rats and the sham-treated ones. In
      rats chronically treated with ECS, the isoproterenol-induced increases in both
      pineal NAT activity and melatonin content were significantly lower than in sham
      treated animals (p < 0.001 for NAT activity; p < 0.005 for melatonin levels;
      Turkey's test). These data show that the pinealocyte beta-adrenoceptor function
      is reduced by chronic, but not acute ECS administration, and that this change is
      not due to the nonspecific stress effect of animal handling or to the acute
      effects of the last of a series of ECS.

PMID- 7740064
TI  - Oral and IP caffeine pharmacokinetics under a chronic food-limitation condition.
AB  - For food-limited rats, serum caffeine was proportional to IP caffeine doses (10
      40 mg/kg) for Cmax and area under the curve [AUC(0-24 h)], whereas the three
      dimethylxanthine (DMX) metabolites of caffeine were disproportional over the dose
      range. Steady-state concentrations of caffeine and the three metabolites were
      evident at the 11th day of chronic, daily caffeine IP 20 mg/kg doses. Both
      caffeine and the three metabolites were dose proportional for Cmax and AUC(0-24
      h) by schedule-induced oral caffeine self-administration within the dose range
      taken (9-38 mg/kg). These results contrast with the nonlinear kinetics of
      caffeine reported for rats under ad lib conditions. Elimination rate constants
      (Kel) remained the same for the two routes, but apparent volume of distribution
      (AVd) and clearance (Cl) were different. The order of the Kel values was caffeine
      > paraxanthine > theophylline > theobromine. The effects of linear vs. nonlinear
      caffeine pharmacokinetics may have distinct implications for the resulting
      pharmacodynamics.

PMID- 7740065
TI  - Dorsomedial hypothalamic GABA regulates anxiety in the social interaction test.
AB  - Blockade of GABAA function in the region of the dorsomedial hypothalamus (DMH) of
      rats is known to elicit a constellation of physiologic responses including
      increases in heart rate (HR), mean arterial blood pressure (BP), respiratory
      rate, and plasma catecholamine levels, as well as behavioral responses such as
      increases in locomotor activity and anxiogenic-like effects as measured in a
      conflict test and the elevated plus-maze test. The aim of the present study was
      to test the effects of microinjecting GABAA antagonists bicuculline methiodide
      (BMI) and picrotoxin, as well as the GABAA agonist muscimol, into the DMH of rats
      placed in the social interaction (SI) test. Muscimol decreased HR and BP but
      increased SI, whereas the GABA antagonists increased HR and BP but decreased SI
      time. Blocking the HR changes elicited by GABAergic drugs injected into the DMH
      with systemic injections of atenolol and atropine methylbromide did not block
      their effects on SI.

PMID- 7740066
TI  - Development of tolerance and reverse tolerance to haloperidol- and SCH23390
      induced cataleptic effects during withdrawal periods after long-term treatment.
AB  - The development of tolerance and reverse tolerance and reverse tolerance to the
      cataleptic effects of selective D1 antagonist, SCH23390, and the mainly D2
      antagonist, haloperidol, was investigated in mice that had been chronically
      treated (7 or 30 days) with haloperidol (1 mg/kg SC), SCH23390 (0.5 mg/kg SC), or
      saline (5 ml/kg SC). In control animals, SCH23390 (0.1-1.0 mg/kg IP) and
      haloperidol (0.1-1.0 mg/kg IP) produced cataleptic responses in a dose-dependent
      manner, although the responses had different time course profiles. SCH23390
      catalepsy had a rapid onset but a short duration, whereas haloperidol catalepsy
      had a slower onset and longer duration. This could be due to differences in lipid
      solubility of the drugs, or at least pertly to an action of the drugs on
      different neuronal pathways. The cataleptic effects of SCH23390 (0.3 mg/kg IP)
      and haloperidol (0.3 mg/kg IP) were significantly reduced in mice when given 24
      h, but not 72 h, after the last dose of a 7 day-pretreatment course (short-term
      treatment) of SCH23390. However, after long-term treatment (30 days) with
      SCH23390, a challenge dose of SCH23390 exhibited reverse tolerance (i.e.,
      increased catalepsy) when given 7-21 days, but not 1-3 days, after the last
      injection of the SCH23390 pretreatment course. In contrast, haloperidol catalepsy
      was not affected by long-term SCH23390 treatment. However, after the last dose of
      long-term haloperidol treatment both SCH23390 and haloperidol exhibited tolerance
      to their cataleptic effects at 1-3 days, a normal response at 7 days, and an
      exaggerated response (reverse tolerance) at 15-21 days.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7740067
TI  - Buprenorphine increases intake of freely available and operant-contingent food in
      satiated rats.
AB  - Opiate administration increases short-term free feeding in satiated rats. The
      feeding effects of the mixed opioid receptor agonist/antagonist buprenorphine
      were examined in both free-feeding and operant chamber paradigms. Buprenorphine
      (0.1 and 0.3 mg/kg) produced significant increases in short-term free feeding
      (i.e., 4 h), an effect enhanced by repeated administration. Buprenorphine's
      effects on operant responding were examined in satiated rats using a fixed ratio
      (FR) 80 (initial pellet) FR 3 (subsequent pellets) reinforcement schedule.
      Buprenorphine (0.03-0.3 mg/kg) decreased latency to begin responding for food,
      and increased total number of pellets consumed in a 1-h session. Increases in
      food intake relative to control were caused by continued responding for food as
      sessions progressed. Naloxone suppressed both the free-feeding and operant
      contingent intake induced by buprenorphine. Thus, buprenorphine increases both
      freely available and lever-press contingent food intake.

PMID- 7740068
TI  - Neonatally administered naltrexone affects several behavioral responses in adult
      rats of both genders.
AB  - The effects of a daily injection of the opioid antagonist naltrexone (NALTX, 1
      mg/kg SC), from birth to weaning day, on several behavioral parameters were
      investigated in adult rats of both genders. This work uses three behavioral
      tests. The use of the open-field test in addition to the holeboard and plus-maze
      tests allows the measurement of complementary parameters, and provided further
      information on diverse components of behavior. The effect of repeated testing
      (habituation) over 3 consecutive days of open-field testing was also assessed. In
      accordance with previous reports, female rats showed higher locomotor activity
      and exploration and a lower level of emotionality than their male counterparts.
      The response of the animals to repeated testing seemed to be both sex and
      treatment dependent. In both males and females, NALTX treatment during the
      preweanling period did not affect locomotor activity, but increased the animals'
      levels of anxiety and emotionality and decreased exploratory behavior. Our
      results indicate that neonatal opioids may play an important role in the
      development of behavioral responses in the adult.

PMID- 7740069
TI  - Isobolographic assessment of the effects of combinations of phenylpropanolamine
      and fenfluramine on food intake in rats.
AB  - Phenylpropanolamine (PPA) suppresses appetite in rats via activation of alpha 1
      adrenergic receptors within the paraventricular hypothalamus (PVN). The
      serotonergic (5-HT) agonist fenfluramine (FEN) is thought to suppress appetite
      via stimulation of 5-HT release within the PVN rather than activation of
      adrenergic receptors. Whether a mixture of these neurochemically distinct
      anorexic drugs will serve as an effective appetite suppressant is unknown. In the
      present experiment, drug-drug interactions between PPA and FEN were explored
      using an isobologram technique. Fixed doses of PPA (0 vs. 5 mg/kg) were combined
      with various doses of FEN (1.25, 2.5, and 5.0 mg/kg) and fixed doses of FEN (0
      vs. 2.5 mg/kg) were combined with various doses of PPA (0, 5, 10, and 15 mg/kg).
      Drug combinations were injected IP 30 min before a 1-h feeding trial in 16-h food
      deprived rats. PPA and FEN were dose-additive in this paradigm, an outcome that
      supports the feasibility of a new appetite suppressant composed of a mixture of
      PPA and FEN.

PMID- 7740070
TI  - Thermoregulatory effects of alkaloids isolated from Wu-chu-yu in afebrile and
      febrile rats.
AB  - Dehydroevodiamine (DeHE) and evodiamine (EVO), alkaloids isolated from a Chinese
      medicinal herb, Wu-chu-yu, exhibit calcium antagonistic activity. Intraperitoneal
      injections of DeHE (5-20 mg/kg) and EVO (2.5-10 mg/kg) caused a dose-related
      hypothermia in afebrile rats at an ambient temperature (Ta) of 20 degrees C.
      Because the heat production of alkaloid-injected rats did not differ from that of
      the controls, the hypothermic effect likely resulted from increased peripheral
      heat loss. This suggestion is supported by the finding that both DeHE and EVO did
      not affect the thermoregulatory response of rats exposed to a Ta of 35 degrees C,
      at which heat loss was maximized. Injection of the same doses of DeHE and EVO
      attenuated the febrile response in a dose-related manner, induced by
      intrahypothalamic injection of exogenous pyrogen. The attenuation of the febrile
      response was associated with a reduction in heat production. Because DeHE and EVO
      did not affect HP in afebrile rats at a Ta of either 20 or 35 degrees C, but
      suppressed the metabolic rate of febrile rats at 20 degrees C, the
      thermoregulatory effect of DeHE and EVO could involve both a calcium-dependent
      increase in heat loss and a suppression in heat production; the latter may only
      be manifested when the set point for thermoregulation is elevated.

PMID- 7740071
TI  - Morphine-induced taste avoidance is attenuated with multiple conditioning trials.
AB  - Morphine has paradoxical effects in learning experiments. The drug can serve as a
      reinforcer in several situations; yet rats avoid tastes paired with morphine,
      much as they avoid tastes paired with an emetic drug such as lithium chloride
      (LiCl). The results of the present experiment indicate that, in contrast with
      LiCl-induced taste avoidance, the strength of morphine-induced avoidance is
      nonmonotonically related to the duration of training. Although taste avoidances
      produced by both drugs are readily established, the morphine-induced avoidance
      (unlike the LiCl-induced avoidance) weakens with continued flavor-drug pairings.
      These results, together with prior findings, suggest that there are distinctive
      features of morphine-induced taste avoidance.

PMID- 7740072
TI  - The NMDA receptor complex modulates clonidine-induced increases in growth hormone
      levels in rats.
AB  - Intraperitoneal administration of clonidine (50 micrograms/kg) produced increases
      in growth hormone levels in male Wistar rats. Pretreatment with NMDA receptor
      antagonists including (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid
      (CPP/NMDA site), ifenprodril (polyamine site), and dizocilpine maleate (MK-801)
      or phencyclidine (PCP) (channel blockers) did not have any significant effect on
      clonidine-induced increases in growth hormone levels. In contrast, pretreatment
      with 5,7-dichlorokynurenic acid and 6,7-dinitroquinoxaline-2,3-dione (DNQX) (NMDA
      receptor-associated glycine site antagonists) significantly attenuated clonidine
      induced increases in growth hormone levels. Attenuation of clonidine's effect on
      growth hormone levels by NMDA receptor-associated glycine site antagonists
      appears most likely due to an interaction between their effects on the NMDA
      receptor complex with growth hormone releasing factor.

PMID- 7740073
TI  - Cortical [3H]ketanserin binding and 5-HT2A receptor-mediated behavioral responses
      in obese Zucker rats.
AB  - Past studies have indicated that genetically obese Zucker (fa/fa) rats are
      hypercorticoid, and that this neuroendocrine alteration plays a key role in the
      syndrome. In keeping with the proposal that glucocorticoids may upregulate
      central 5-HT2A receptors, we have studied the effects of acute and repeated 5
      HT2A receptor stimulation by 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI)
      in lean and obese Zucker rats. Acute injection of DOI (2 mg/kg, SC) elicited a
      lower number of head shakes in obese rats compared to that measured in lean rats.
      Conversely, neither DOI-elicited decreases in food intakes and body weights nor
      cortical [3H]ketanserin binding were affected by obesity. In rats repeatedly
      pretreated with DOI, biochemical and functional indices of 5-HT2A receptor
      downregulation failed to reveal an effect of obesity. It is suggested that 5-HT2A
      receptor-mediated functions, but not their downregulation, may be differentially
      affected in the hypercorticoid obese Zucker rat.

PMID- 7740074
TI  - Fluorescence of tyrosine and tryptophan in proteins using one- and two-photon
      excitation.
AB  - We examined the emission spectra of tyrosine- and tryptophan-containing proteins
      using one-photon (270-310 nm) and two-photon (565-610 nm) excitation. Emission
      spectra for two-photon excitation of native and denatured human serum albumin and
      of three purine nucleoside phosphorylases indicated an absence of the tyrosine
      emission normally seen for one-photon excitation below 290 nm. We examined the
      one-photon and two-photon excitation spectra of tyrosine-tryptophan mixtures to
      determine the origin of selective excitation of the tryptophan residues. These
      results confirmed a short-wavelength shift of the tyrosine two-photon excitation
      spectrum relative to that of tryptophan, as recently reported by Rehms and Callis
      (1993) Chem. Phys. Lett. 208, 276-282.

PMID- 7740075
TI  - Trapping of nitric oxide formed during photolysis of sodium nitroprusside in
      aqueous and lipid phases: an electron spin resonance study.
AB  - Photolytic decomposition of sodium nitroprusside (SNP), a widely used
      nitrovasodilator, produced nitric oxide (.NO), which was continuously monitored
      by electron spin resonance (ESR) spectroscopy. The .NO present in the aqueous or
      the lipid phase was trapped by either a hydrophilic or a hydrophobic nitronyl
      nitroxide, respectively, to form the corresponding imino nitroxide. The
      conversion of nitronyl nitroxide to imino nitroxide was monitored by ESR
      spectrometry. The quantum yield for the generation of .NO from SNP, measured from
      the rate of decay of nitronyl nitroxide, was 0.201 +/- 0.007 and 0.324 +/- 0.01
      (mean +/- SD, n = 3) at 420 nm and 320 nm, respectively. The action spectrum for
      .NO generation was found to overlap the optical absorption spectrum of SNP
      closely. A mechanism for the reaction between SNP and nitronyl nitroxide in the
      presence of light is proposed and computer-aided simulation of this mechanism
      using published rate constants agreed well with experimental data. The
      methodology described here may be used to assay .NO production continuously
      during photoactivation of .NO donors in aqueous and lipid environments.
      Biological implications of this methodology are discussed.

PMID- 7740076
TI  - Selective DNA thymine dimerization during UVA irradiation in the presence of a
      saturated pyridopsoralen.
AB  - It has been recently shown that UVA (320-400 nm) irradiation of DNA in the
      presence of pyridopsoralens induces the formation of thymine cyclobutane dimers
      in addition to monoadducts. In this work, we measured the potency of a saturated
      pyridopsoralen to photosensitize DNA, despite its inability to covalently attach
      to DNA. First, from spectroscopic fluorescence measurements, we have shown that
      both analogs, saturated and unsaturated pyridopsoralens, namely 4',5'-dihydro-7
      methyl-pyrido[3,4-c]psoralen (DH-MePyPs) and 7-methylpyrido[3,4-c]psoralen,
      exhibit a similar global affinity for DNA. Secondly, we demonstrated, by
      footprinting experiments, that exposure of a DNA sequence to 365 nm UV radiation
      in the presence of DH-MePyPs results in selective cyclobutane thymine
      dimerization. Thymines located in the immediate proximity of the 5'-TA-3' step
      are exclusively affected and the frequency of this photoprocess depends on
      flanking sequences. We thus probe a selective thymine dimer photosensitizer.
      Results are discussed in terms of drug affinity and physical properties of the
      helix at the binding site.

PMID- 7740077
TI  - Singlet oxygen luminescence spectra: a comparison of interferometer- and grating
      based spectrometers.
AB  - The current trend in methodology for determining IR and near-IR absorption
      spectra is to employ interferometer-based instruments to replace the
      monochromator-based devices used heretofore. As a dispersion element, the
      interferometer offers major improvements in spectral resolution (Connes
      advantage), light throughput (Jacquinot advantage) and data acquisition through
      multiplexing (Felgett advantage). We have compared signal-to-noise (S/N) ratios
      of grating-based and interferometer-based instruments for making spectral
      determinations of near-IR luminescence. Our results show that under identical
      excitation and detector conditions the interferometer instrument easily
      outperforms the grating, giving a 10-fold improvement in S/N at high signal
      amplitude (A488nm = 0.97) and a 20-fold improvement when the signal amplitude is
      low (A488nm = 0.06). Although some spectral resolution is sacrificed when scan
      times on the Fourier transform (FT)IR are significantly shortened, the S/N ratio
      was found only to decrease by a factor of 2 for a 10-fold decrease in scan time.
      This adds to the advantages of the FTIR technique because the S/N will thus
      improve for the same total acquisition time.

PMID- 7740078
TI  - Reversion profiles of coolwhite fluorescent light compared with far ultraviolet
      light: homologies and differences.
AB  - General Electric and Sylvania 15 W coolwhite fluorescent lamps emit roughly 6% of
      their total irradiance as light in the UV spectrum. Illumination of sensitive
      Salmonella tester strains results in both lethal and mutagenic activities. In
      contrast, comparable Philips lamps emit lower levels of UV light, especially UVB,
      and exhibit no detectable lethal or mutagenic effects. The spectra of mutations
      induced by General Electric coolwhite lamps in histidine-requiring base
      substitution mutants hisG46 and hisG428 ("reversion profiles") resemble
      mutagenesis by far UV light (UVC) and differ quite markedly from the spectra of
      mutations that occur spontaneously. Coolwhite and UVC reversion profiles are not
      identical, however. The percentage of C to A transversion mutations induced in
      hisG46 are elevated over those found after UVC treatment, and a strong bias for
      one particular class of tandem base substitutions (TAA-->TGT) prevails after
      treatment of hisG428 with coolwhite light, a bias not observed with UVC.
      Increased attention needs to be given to minimization of exposure to UV light
      from fluorescent lamps commonly used in homes and workplaces.

PMID- 7740079
TI  - Using cell-fractionation and photochemical crosslinking methods to determine the
      cellular binding site(s) of the antitumor drug DMP 840.
AB  - In order to understand its mechanism of action we have begun an effort to better
      define the cellular target of action of the experimental antitumor agent DMP 840
      (NSC D640430; (R,R)-2,2'-(1,2-ethanediylbis(imino-(1-methyl-2,1-ethanediyl)))-bi
      s(5- nitro-1H-benz(de)isoquinoline-1,3-(2H)-dione) dimethanesulfonate). Using a
      combination of gentle cell fractionation procedures and a previously unidentified
      photochemical crosslinking reaction, we have shown that after the drug is added
      to cultured Clone A cells, more than 80% of the drug that is found associated
      with cells partitions to the chromatin-containing structural framework of the
      cell and that the primary target after crosslinking with 360 nm light is DNA.
      While DMP 840 photoreacts quite efficiently with purified RNA in vitro, no
      photoattachment of the drug to RNA was observed in cells. In vitro photochemical
      studies also reveal that while GC-rich DNA is a preferred target for drug
      interaction, AT-rich DNA is more active in the photochemical crosslinking
      reaction. These results suggest that DMP 840 probably kills cells by interfering
      with DNA-metabolic processes, and that the drug and its derivatives are likely to
      be useful photoactive molecular probes for investigating higher order chromatin
      structures in cells.

PMID- 7740080
TI  - Formation of protein-bound 3,4-dihydroxyphenylalanine in collagen types I and IV
      exposed to ultraviolet light.
AB  - Collagen was exposed to an ultraviolet (UV) lamp that emitted predominantly in
      the UVB range. The cross-linking of collagen type I and type IV by UV irradiation
      was observed. Amino acid analyses revealed that Tyr residues in both collagen
      types I and IV were decreased by irradiation. In collagen type IV, losses of His
      and Met residues were also observed. These losses of collagen type IV may be due
      to the degradation of Trp, which exists in collagen type IV and decreased
      drastically during UV irradiation. To clarify the mechanism of Tyr modification
      in both types of collagen, the degradation products of Tyr were analyzed.
      Dityrosine, which is a dimer of the Tyr residue, could not be detected in the
      acid hydrolysates of UV-irradiated collagen. However, 3,4-dihydroxyphenylalanine,
      DOPA, was detected in the hydrolysates using HPLC with an electrochemical
      detector. The amounts of DOPA in the acid hydrolysates of collagen exposed to UV
      light for 24 h were approximately 350 pmol/mg protein (collagen type IV) and 80
      pmol/mg protein (collagen type I). The DOPA formed may partially contribute to
      photoaging of the skin.

PMID- 7740081
TI  - Induction of cyclobutane pyrimidine dimer photolyase in cultured fish cells by
      fluorescent light and oxygen stress.
AB  - The expression of a gene for photolyase in RBCF-1 cells, a line of cultured
      goldfish cells, is known to be enhanced by fluorescent light. We have now found
      that H2O2 is another strong inducer of cyclobutane pyrimidine dimer photolyase.
      Northern blot analysis suggested that regulation by H2O2 occurs at the
      transcriptional level and the time course of induction of photolyase by H2O2 was
      similar to that by fluorescent light. Treatment with fluorescent light in the
      presence of riboflavin, which is known as an endogenous photosensitizer, also
      enhanced the induction of photolyase. These results suggest the involvement of
      oxygen stress in the induction of photolyase by fluorescent light. A cell clone
      with high-level expression of the goldfish gene for photolyase was obtained by
      transfection with plasmids that expressed the goldfish photolyase in OL32 cells
      derived from another fish, the medaka (Oryzias latipes). The induction of the
      medaka gene for photolyase was not affected by the high-level expression of the
      goldfish gene for this enzyme.

PMID- 7740082
TI  - The effects of multiple UV exposures on HIV-LTR expression.
AB  - Previous studies have shown that cellular stress agents such as UV radiation
      induce transcription from the long terminal repeat (LTR) of the human
      immunodeficiency virus (HIV). Using HeLa cells stably transfected with the HIV
      LTR sequence, which transcriptionally drives the chloramphenicol acetyl
      transferase (CAT) reporter gene, we examined the effects of multiple exposures to
      UVC (254 nm) on HIV-LTR-CAT expression. Low doses (< or = 5 J m-2) had no effect
      on CAT expression, but up to 29-fold induction was observed with 10 J m-2 when
      cells were harvested 48 h after completion of the exposure. Little difference was
      noted in induction levels when cells were exposed to one 25 J m-2 dose, viable
      cells were harvested at 24 h, 48 h or 72 h, and cell lysates were assayed for CAT
      expression. Two sequential 12.5 J m-2 exposures, given 24 h apart, resulted in an
      additive effect on CAT expression; these two exposures produced CAT activity
      equivalent to that induced following a single 25 J m-2 dose. This additive effect
      was not evident at the lower doses (< or = 5 J m-2) or at the higher doses.
      Maximal induction was observed using doses from 25 to 37.5 J m-2. Multiple
      exposures with either the low (< or = 5 J m-2) or high doses (> 25 J m-2) did not
      result in an additive effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740084
TI  - Distribution of temoporfin, a new photosensitizer for the photodynamic therapy of
      cancer, in a murine tumor model.
AB  - The biodistribution of temoporfin (tetra[m-hydroxyphenyl]chlorin, m-THPC), a
      recently developed photosensitizer, was investigated in BALB/c mice. The drug was
      administered intravenously (0.35-0.75 mumol/kg) to tumor-free mice or to mice
      implanted with the Colo 26 colorectal carcinoma. Blood and tissue samples were
      collected for up to 96 h post-dose. Drug concentrations were determined by HPLC
      coupled to photometric detection at 423 nm. Concentrations in blood and liver
      fell relatively rapidly such that blood concentrations at later time points were
      below the limit of detection. Tumor concentrations rose at first and then
      remained constant from 24 h. Temoporfin concentrations in some tissues, notably
      heart and skeletal muscle, declined only slowly when compared to blood. The
      tumor: tissue ratios for those organs that showed a more rapid decline in
      temoporfin concentrations were higher at later times, whereas in tissues such as
      muscle the ratio remained relatively constant. The organs with the highest
      tumor:tissue ratios were small intestine (8.6), liver (6.9) and skeletal muscle
      (5.0).

PMID- 7740083
TI  - Inhibition of the ATPase activity of P-glycoprotein by porphyrin
      photosensitization of multidrug-resistant cells in vitro.
AB  - The effectiveness of photodynamic therapy against P-glycoprotein ATPase activity
      in multidrug-resistant cells was studied. Chinese hamster ovary AUXB1 (drug
      sensitive) and CR1R12 (multidrug-resistant) cell lines were compared with respect
      to uptake of 14C-polyhematoporphyrin and porphyrin photosensitization.
      Phototoxicity of Photofrin was similar in both cell lines, and no major
      differences in uptake or efflux of 14C-polyhematoporphyrin were observed.
      Porphyrin photosensitization in vitro of CR1R12 cells or isolated plasma
      membranes from these cells caused inhibition of P-glycoprotein ATPase activity.
      Application of porphyrin photosensitization at a sublethal level to CR1R12 cells
      resulted in a small but significant increase in adriamycin-induced cytotoxicity.
      The hydrophobic "picket-fence" porphyrin, meso-tetrakis-(o
      propionamidophenyl)porphyrin, alpha,alpha,alpha,beta-isomer, was more inhibitory
      toward P-glycoprotein ATPase activity than the two less hydrophobic porphyrins
      tetraphenylporphine tetrasulfonate and Photofrin.

PMID- 7740085
TI  - Analysis of viral DNA, protein and envelope damage after methylene blue,
      phthalocyanine derivative or merocyanine 540 photosensitization.
AB  - Although numerous photosensitizers have been used experimentally to decontaminate
      viruses in cellular blood components, little is known about their mechanisms of
      photoinactivation. Using M13 bacteriophage and vesicular stomatitis virus (VSV)
      as model viruses, we have investigated alteration of the viral genome, protein
      and envelope after phototreatment. Methylene blue (MB) and aluminum
      phthalocyanine tetrasulfonate (AlPcS4) phototreatment inactivated bacteriophage
      M13 and decreased the fraction of single-stranded circular genomic DNA (sc-DNA)
      by converting it to linear form. This conversion was enhanced by treating the
      extracted DNA with piperidine at 55 degrees C. Piperidine-labile breaks were well
      correlated to phage survival (5.1% sc-DNA at 1.7% phage survival for MB) under
      conditions where only minor differences were seen in the relative abundance of
      M13 coat protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE). Neither aluminum phthalocyanine (AlPc) nor merocyanine 540 (MC540)
      inactivated M13 nor were there significant changes observed in DNA and coat
      protein. Methylene blue, AlPcS4 and AlPc inactivated VSV and inhibited fusion of
      the virus envelope to Vero cells at pH 5.7 (i.e. with plasma membrane). However,
      the degree of this inhibition was small compared to the extent of virus
      inactivation (43% inhibition vs. 4.7 log10 or 99.998% inactivation, for MB). In
      contrast, an antibody to VSV G-spike protein inhibited fusion at pH 5.7 by 52%
      with a concomitant decline in VSV infectivity of 0.15 log10 (30%). Few changes
      were observed in the relative abundance of G protein for MB and AlPcS4
      phototreated samples and no additional protein bands were observed on SDS
      PAGE.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740086
TI  - Sensitivity of Porphyromonas and Prevotella species in liquid media to argon
      laser.
AB  - The phototoxicity of argon laser irradiation was studied in aqueous suspensions
      of Porphyromonas endodontalis (American Type Culture Collection [ATCC] 35406),
      Porphyromonas gingivalis (ATCC 33277), Prevotella denticola (ATCC 33184) and two
      strains of Prevotella intermedia (ATCC 15033 and 49046), all "black-pigmented
      bacteria," BPB, that accumulate cellular porphyrins. Several of these species
      have been implicated in the etiology of periodontal disease. Non-black-pigmented
      bacteria were also studied to test the specificity of irradiation as a potential
      photodynamic treatment for periodontal infections. Cell suspensions were
      irradiated with an argon laser at fluences of 20-200 J/cm2. When cultured in
      hemin-supplemented media, ATCC 15033 was the most sensitive to irradiation.
      However, a second strain of the same species (ATCC 49046) was resistant. The
      photosensitivity of other species ranked ATCC 33277 > 35406 = 33184 = 35496. When
      hemin was replaced in media by hemoglobin, ATCC 33277 became resistant to
      irradiation. Protoporphyrin IX content in BPB cells was shown not to be a major
      factor determining photosensitivity. Oxygen was required during irradiation for
      BPB species to be affected. Non-black-pigmented bacteria were much less sensitive
      to irradiation than BPB.

PMID- 7740087
TI  - Time-dependent photodynamic damage to blood vessels: correlation with serum
      photosensitizer levels.
AB  - We have used the technique of dynamic capillaroscopy to study the time-course of
      photodynamic vascular occlusion in mice injected intraperitoneally with either of
      two photosensitizers; hematoporphyrin esters (HPE) or meso-tetrahydroxyphenyl
      chlorin (mTHPC). The peak of vascular occlusion induced by HPE coincided in time
      with peak serum levels of this photosensitizer (about 3 h after injection).
      However, there was also a second peak of occlusive activity at about 12 h after
      injection, at which time serum HPE was falling monotonically. In the case of
      mTHPC, no peak of occlusive activity was seen at 3 h after injection, even though
      the serum levels of this photosensitizer, like those of HPE, were highest around
      this time. Instead, a steady rise in photosensitizing activity was observed,
      peaking at 11 h. This decoupling between serum drug levels and vascular
      photosensitization--partial for HPE and complete for mTHPC-suggests that direct
      photosensitization of endothelial cells is unlikely wholly to explain the
      vascular collapse. Instead, there must be either another compartment that
      accumulates photosensitizer more slowly and in which photodynamic activity has an
      indirect effect on the blood capillaries or a slow metabolic transformation of
      mTHPC into a more active sensitizer.

PMID- 7740088
TI  - Sensitivity of activated murine peritoneal macrophages to photodynamic killing
      with benzoporphyrin derivative.
AB  - This study compared the ability of highly purified resting and activated DBA/2
      mouse peritoneal macrophages to survive treatment with the photosensitizer
      benzoporphyrin derivative (BPD, verteporfin) and light. Culture of macrophages
      with recombinant murine interferon-gamma (rIFN-gamma, 100 U/mL) for 72 h imparted
      a phenotypic and functional activation by dramatically increasing cell surface
      expression of major histocompatibility complex Class II (Ia) molecules and the
      formation of nitric oxide. The rIFN-gamma-activated macrophages were
      significantly (P < 0.05) more sensitive (lethal dose to cause a 50% reduction in
      cell survival, LD50 = 14.4 +/- 1.1 ng/mL) to photodynamic killing with BPD and
      light (10 J/cm2) than cells (LD50 = 18.2 +/- 2.0 ng/mL) cultured in medium alone.
      In contrast, macrophages treated with different concentrations of bacterial
      lipopolysaccharide (LPS) were as resistant or more resistant to photodynamic
      killing than cells cultured in medium alone. No cytotoxic effect of BPD was
      detected in cultures containing the drug but protected from light. Comparable
      amounts of BPD were taken up in vitro by unactivated and rIFN-gamma-activated
      macrophages, as detected by flow cytometric analysis. However, cells cultured
      with LPS (10 micrograms/mL) took up more BPD than macrophages cultured in medium
      alone or with rIFN-gamma. The DBA/2 P815 mastocytoma cells took up greater
      amounts of the drug and were subsequently more vulnerable to treatment with BPD
      and light (LD50 = 6.9 ng/mL) than macrophages cultured under any condition. The
      explanation for the increased vulnerability of rIFN-gamma-activated macrophages
      and the greater resistance of LPS-activated macrophages, relative to medium
      cultured macrophages, to photodynamic killing with BPD is uncertain.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7740089
TI  - Long-term working memory.
AB  - To account for the large demands on working memory during text comprehension and
      expert performance, the traditional models of working memory involving temporary
      storage must be extended to include working memory based on storage in long-term
      memory. In the proposed theoretical framework cognitive processes are viewed as a
      sequence of stable states representing end products of processing. In skilled
      activities, acquired memory skills allow these end products to be stored in long
      term memory and kept directly accessible by means of retrieval cues in short-term
      memory, as proposed by skilled memory theory. These theoretical claims are
      supported by a review of evidence on memory in text comprehension and expert
      performance in such domains as mental calculation, medical diagnosis, and chess.

PMID- 7740090
TI  - A cognitive-affective system theory of personality: reconceptualizing situations,
      dispositions, dynamics, and invariance in personality structure.
AB  - A theory was proposed to reconcile paradoxical findings on the invariance of
      personality and the variability of behavior across situations. For this purpose,
      individuals were assumed to differ in (a) the accessibility of cognitive
      affective mediating units (such as encodings, expectancies and beliefs, affects,
      and goals) and (b) the organization of relationships through which these units
      interact with each other and with psychological features of situations. The
      theory accounts for individual differences in predictable patterns of variability
      across situations (e.g., if A then she X, but if B then she Y), as well as for
      overall average levels of behavior, as essential expressions or behavioral
      signatures of the same underlying personality system. Situations, personality
      dispositions, dynamics, and structure were reconceptualized from this
      perspective.

PMID- 7740091
TI  - A life-span theory of control.
AB  - A life-span theory of development is presented that is based on the concepts of
      primary and secondary control. Primary control refers to behaviors directed at
      the external environment and involves attempts to change the world to fit the
      needs and desires of the individual. Secondary control is targeted at internal
      processes and serves to minimize losses in, maintain, and expand existing levels
      of primary control. Secondary control helps the individual to cope with failure
      and fosters primary control by channeling motivational resources toward selected
      action goals throughout the life course. Primary control has functional primacy
      over secondary control. An analysis of extensive and diverse literatures spanning
      infancy through old age shows that trade-offs between primary and secondary
      control undergo systematic shifts across the life course in response to the
      opportunities and constraints encountered.

PMID- 7740092
TI  - Simulation of expert memory using EPAM IV.
AB  - EPAM is a theory of the processes of human perception and memory, first
      programmed for a computer by E. A. Feigenbaum in 1959, that has shown an
      excellent fit to experimental data from a wide variety of psychological tasks.
      Over the years, it has been progressively extended to new domains without
      essential change in its central mechanisms. This article examines EPAM IV, a
      version extended to account for expert memory, especially the work in recent
      years by Chase and Ericsson (1981, 1982) and Staszewski (1988a, 1988b, 1990).
      EPAM IV has also been adapted to deal with numerous other short-term and long
      term memory tasks, which will be reported elsewhere. The main modifications of
      EPAM that are relevant to the serial recall task examined in this article are a
      schema in long-term memory (called a retrieval structure) created by the expert's
      learning and the addition of an associative search process in long-term memory.
      These new components operate in close interaction with the other EPAM structures
      to match the observed behavior. EPAM IV reproduces all of the phenomena explained
      previously by EPAM III and in addition gives an accurate detailed account of the
      performance (studied by Staszewski) of an expert recalling long sequences of
      digits. The theory substantially revises, improves, and extends Chase and Simon's
      earlier "chunking" explanation of expert memory.

PMID- 7740093
TI  - Separation of low-level and high-level factors in complex tasks: visual search.
AB  - A method for assessing the role of low-level factors in complex tasks is
      described. The method, which involves comparing simple-discrimination performance
      and complex-task performance for the same stimuli, was used to assess the role of
      low-level factors in multiple-fixation visual search. In one experiment, the
      target and background were composed of line segments that differed in color,
      orientation, or both; in another, target and background were composed of filtered
      noise textures that differed in spatial frequency, orientation, or both. Most of
      the variance in search time was found to be predictable from the discrimination
      data, suggesting that low-level factors often play a dominant role in limiting
      search performance. A signal-detection model is presented that demonstrates how
      current psychophysical models of visual discrimination might be generalized to
      obtain a theory that can predict search performance for a wide range of stimulus
      conditions.

PMID- 7740094
TI  - The experience of regret: what, when, and why.
AB  - This article reviews evidence indicating that there is a temporal pattern to the
      experience of regret. Actions, or errors of commission, generate more regret in
      the short term; but inactions, or errors of omission, produce more regret in the
      long run. The authors contend that this temporal pattern is multiply determined,
      and present a framework to organize the divergent causal mechanisms that are
      responsible for it. In particular, this article documents the importance of
      psychological processes that (a) decrease the pain of regrettable action over
      time, (b) bolster the pain of regrettable inaction over time, and (c)
      differentially affect the cognitive availability of these two types of regrets.
      Both the functional and cultural origins of how people think about regret are
      discussed.

PMID- 7740095
TI  - A measurement-theoretic analysis of the fuzzy logic model of perception.
AB  - The fuzzy logic model of perception (FLMP) is analyzed from a measurement
      theoretic perspective. FLMP has an impressive history of fitting factorial data,
      suggesting that its probabilistic form is valid. The authors raise questions
      about the underlying processing assumptions of FLMP. Although FLMP parameters are
      interpreted as fuzzy logic truth values, the authors demonstrate that for several
      factorial designs widely used in choice experiments, most desirable fuzzy truth
      value properties fail to hold under permissible rescalings, suggesting that the
      fuzzy logic interpretation may be unwarranted. The authors show that FLMP's
      choice rule is equivalent to a version of G. Rasch's (1960) item response theory
      model, and the nature of FLMP measurement scales is transparent when stated in
      this form. Statistical inference theory exists for the Rasch model and its
      equivalent forms. In fact, FLMP can be reparameterized as a simple 2-category
      logit model, thereby facilitating interpretation of its measurement scales and
      allowing access to commercially available software for performing statistical
      inference.

PMID- 7740096
TI  - Diagnostic criteria for use in psychosomatic research.

PMID- 7740097
TI  - Visual memory impairment in patients with obsessive-compulsive disorder: a
      controlled study.
AB  - Memory processes were compared in 26 patients presenting DSM-III-R obsessive
      compulsive disorder (OCD) with 20 sex-, age- and education-matched normal
      controls. A significant between-group difference was found: visual memory was
      significantly lower in OCD, whereas no significant between-group differences in
      verbal memory were observed. A subsample of 17 OCD were also compared with the 20
      control subjects on an explicit-memory free-recall task and an implicit-memory
      completion task using neutral, obsessive and guilt-responsibility words to test
      the effects of an emotional verbal input on memory functioning. No between-group
      difference was found, suggesting that emotionally laden word processing did not
      modify implicit and explicit memory performances.

PMID- 7740098
TI  - Abnormal oral sensory perception in patients with a history of anorexia nervosa
      and the relationship between physiological and psychological improvement in this
      disease.
AB  - 14 patients with a history of anorexia nervosa (AN) (mean duration 7.1 years)
      were divided into two groups according to whether they were still amenorrheic
      (group I, n = 6) at a significantly lower body weight or at normal stable weight
      with eumenorrhea (group II, n = 8); 26 age-matched students served as the control
      group. Psychological testing included the Eating Disorder Inventory (EDI), shadow
      silhouette size rating, and a new test of oral appreciation of different sized
      cubes. In groups I and II, oral misperception of medium and large sizes was
      significantly greater than visual-tactile appreciation; and all cube sizes,
      however presented, were overexaggerated when compared to the controls. Group II
      subjects had EDI scores and ideal body weight choices similar to those of group
      I. Thus, in AN, in addition to visual misperception, there may be a more
      generalized problem of size conceptualization including oral appreciation. These
      findings also suggest that improvement in body weight and menstrual function, as
      in group II, does not necessarily imply psychological recovery in AN.

PMID- 7740099
TI  - Urinary excretion of catecholamines during the first months after delivery.
AB  - The urinary excretion of free catecholamines was assessed in 17 women 3 times
      after delivery; after 3 weeks, 6 weeks and 6 months, respectively. Relatively
      high levels were found both for adrenaline and noradrenaline excretion, on the
      first and third occasions, with significantly lowered levels on the second one.
      Mothers who had had a negative experience of their delivery (according to
      interview) as well as mothers who felt tired during the mid-phase of the follow
      up (according to diaries) had very small variations in catecholamine excretion
      and did not show increased levels 6 months after delivery. Whether the mother
      experienced her infant as crying or not had no significant association with
      catecholamine output.

PMID- 7740100
TI  - Psychophysiological responses of borderline hypertensives in two experimental
      situations.
AB  - Given the contradictory reports concerning psychophysiological reactivity of
      hypertensives this issue was reexamined. In contrast to the large majority of
      studies, the hypertensive sample should not be made up of patients in medical
      care and the control group should be comparable in all relevant aspects other
      than blood pressure. Twelve male subjects with blood pressure values in the
      borderline range and 12 normotensive controls were recruited from a blood
      donation program. Experiments consisted of two parts with baseline, stress and
      follow-up. Stressors were a short distressing movie and mental arithmetic.
      Systolic and diastolic blood pressure (SBP and DBP), heart rate (HR), skin
      conductance level (SCL) and number of spontaneous electrodermal fluctuations (SF)
      were assessed in 2-min intervals, plasma adrenaline and noradrenaline once during
      baselines, stress 2 and follow-up 2. Hypertensives exhibited significantly higher
      SPB levels, and partially elevated values for DBP, HR and SCL. Response reactions
      to stressors, however, did not differ between groups. There was no evidence that
      psychophysiological adaptation during stress and recovery thereafter was impaired
      in hypertensives. Our results do not support the reactivity hypothesis of
      hypertension. Possible reasons for our failure to replicate findings from other
      studies are discussed.

PMID- 7740101
TI  - Chronic pain and suicide.

PMID- 7740102
TI  - Consultation-liaison research: the use of differing perspectives.
AB  - Slavney and McHugh have discussed the four perspectives in psychiatry in respect
      to their strengths and weaknesses. Research in consultation-liaison psychiatry is
      reviewed by considering the various perspectives that such studies utilize. Early
      studies utilized the life story methodology and the disease model. The life
      history approach considers each patient as a unique subject whose developmental
      vicissitudes have meaningful associations. These studies were often viewed
      through a psychoanalytic theory. The disease model demands syndromal
      identification so that etiologic factors, whether biological, psychological or
      social, may eventually be discovered. More contemporary investigations use the
      dimensional measurement of intersubject differences that allow better designation
      of personality. The fourth perspective of motivated behavior offers a method of
      studying goal-directed activity such as substance abuse, eating pathology, and
      sleep disorders. Consultation-liaison studies using each framework are reviewed.

PMID- 7740103
TI  - Milestones and future trends in solid organ transplantation.
AB  - The past 35 years have been marked by tremendous progress in our understanding of
      the biologic basis for solid organ graft rejection and acceptance. Although still
      controversial, solid organ transplantation has become accepted as effective
      therapy of end-stage disease of the major thoracic and abdominal viscera.
      Progress has come in small increments and quantum leaps. Better control of immune
      suppression has been the most critical factor, but improvements in surgical
      techniques and technical advances, such as better donor organ harvesting and
      preservation, have played essential roles. The milestones in the development of
      successful organ transplantation and the current status and challenges are
      reviewed and the most promising future trends in this exciting field are
      discussed in this article.

PMID- 7740104
TI  - Clinical indications, recipient evaluation, surgical considerations, and the role
      of CT and MR in renal transplantation.
AB  - Although the clinical indications and basic surgical techniques have not changed
      significantly in recent years, overall rates of patient and graft survival have
      shown steady improvement. This is because of newer, more effective
      immunosuppression regimens. Radiologists play a vital role in the detection and
      diagnosis of various postoperative complications after renal transplantation. CT
      is ideally suited for the evaluation of patients in whom abscess or malignancy is
      suspected.

PMID- 7740105
TI  - Sonography of renal transplantation.
AB  - Marked improvements in graft survival have made renal transplantation the
      treatment of choice for end-stage renal disease. Ultrasound, because it is an
      accurate and noninvasive screening examination for graft dysfunction, clearly has
      had an impact upon graft survival rates. Gray scale sonography easily detects
      hydronephrosis and perinephric fluid collections. Vascular complications of
      transplantation--AVFs, pseudoaneurysms, arterial/venous thrombosis and stenosis-
      are readily identified by color and duplex Doppler sonography. Initial enthusiasm
      for the gray scale and Doppler identification of acute rejection largely has been
      proved to be unfounded. Ultrasound guidance, however, clearly minimizes the risk
      and discomfort of definitive percutaneous renal transplant biopsy.

PMID- 7740106
TI  - Angiography and interventional aspects of renal transplantation.
AB  - Interventional techniques play key roles in the management of the renal
      transplant donor and recipient. With prompt diagnosis and intervention,
      postoperative vascular and urologic complications frequently may be treated by
      nonsurgical means. Current concepts in percutaneous intervention for renal
      transplant patients are discussed. Topics include transluminal angioplasty of
      arterial stenoses, treatment of arterial or venous occlusion, embolization of
      intrarenal arteriovenous fistula or pseudoaneurysm, management of periallograft
      fluid collections, and therapy for urinary obstruction or leak.

PMID- 7740107
TI  - Radionuclide imaging in organ transplantation.
AB  - This article addresses the utility of radionuclide imaging for evaluating
      functional and anatomic integrity of transplanted liver, kidney, pancreas, heart,
      and lung. Information about how to interpret routine nuclear medicine procedures
      for vascular and surgical complications as well as rejection after
      transplantation is also presented. The role of new radiopharmaceuticals is
      discussed briefly.

PMID- 7740108
TI  - Presurgical evaluation of the liver transplant candidate.
AB  - Determination of liver transplant candidacy requires an integrated approach
      contingent upon clinical, surgical, and radiologic evaluation. Imaging patients
      with end-stage liver disease is a challenging yet fascinating task. Chest
      radiographs, ultrasound with Doppler, and unenhanced and biphasic contrast CT
      provide sufficient preoperative information about the majority of patients.
      Problematic cases, however, may require a multimodality approach, for which chest
      CT, invasive abdominal CT techniques, MR imaging, cholangiography, angiography,
      and biopsy have all been useful adjuncts. In addition to providing important
      information for surgical planning, the radiologist must carefully look for any
      evidence of malignancy or other conditions that jeopardize successful OLTX and
      threaten meaningful postoperative survival.

PMID- 7740109
TI  - Evaluation of the transplanted liver and postoperative complications.
AB  - This article presents a brief review of posthepatic transplantation anatomy and a
      synopsis of the role of imaging in posthepatic transplantation complications.
      Screening ultrasonography is used to detect vascular stenosis or occlusion. T
      tube cholangiography is used to detect biliary leak or obstruction. Thoughtful
      use of conventional radiographs, ultrasonography, CT, percutaneous
      cholangiography, and MR imaging for problem solving in detection and management
      of complications, such as abdominal fluid collections, can make the difference
      between graft survival or failure.

PMID- 7740110
TI  - Angiography and interventional procedures in liver transplantation.
AB  - Over the past several years, operative techniques, postoperative care, and
      immunosuppressive therapy have advanced steadily, allowing 5-year survival for
      liver transplantation to increase from 20% 15 years ago to 65% today. Biliary and
      vascular complications, however, remain causes of significant morbidity and
      mortality to the liver transplant patient. The interventional radiologist is an
      integral part of the multidisciplinary team necessary for optimization of care of
      the liver transplant patient. In this article, interventional techniques in the
      management of the liver transplant patient are addressed. Topics discussed
      include preoperative evaluation, methods of vascular and biliary reconstruction,
      and diagnosis and management of postoperative complications.

PMID- 7740111
TI  - Heart-lung and lung transplantation.
AB  - Lung and heart-lung transplantation have evolved into successful therapeutic
      options in patients with end-stage cardiopulmonary disease. Imaging studies
      extend from pretransplant evaluation to posttransplant monitoring for
      complications. Although many radiologic features are considered nonspecific,
      improved understanding of underlying pathologic and physiologic conditions unique
      to this population will enhance the clinical impact of the radiologist involved
      in a transplantation program.

PMID- 7740112
TI  - Imaging of pancreas transplants.
AB  - The pancreas transplant is difficult to monitor both clinically and by imaging.
      Complications such as thrombosis, infection, pancreatitis, bleeding, anastomotic
      leak, or rejection may quickly progress to transplant failure. Ultrasound, CT, MR
      imaging, fluoroscopy, nuclear scintigraphy, and angiography may be used to help
      define the etiology of transplant compromise; however, all have marked
      limitations, and none has proved to be the study of choice. The surgeon and
      radiologist must carefully coordinate clinical suspicion with the strengths of
      the various modalities to optimize a timely diagnosis.

PMID- 7740113
TI  - Intestinal and multivisceral transplantation.
AB  - Intestinal transplantation for treatment of irreversible intestinal failure is
      the newest of the transplantation operations to be developed for clinical use.
      Because the bowel is more vulnerable to rejection than heart, lung, kidney,
      liver, or pancreas, practical clinical intestinal transplantation has been
      relatively slow to develop and is still in its infancy. Imaging studies play an
      important role in the initial evaluation of the residual native gastrointestinal
      tract for patients who are potential candidates for enteric implant. After
      transplantation, gastrointestinal contrast studies help monitor the recovery of
      gastrointestinal function and permit early detection of postoperative technical
      complications. CT, ultrasound, and angiography are useful for diagnosis and in
      some cases treatment of a variety of posttransplantation complications.

PMID- 7740114
TI  - [Magnetic resonance tomography in trauma of the knee joint].
AB  - Technical improvements of MRI have significantly improved the visualization of
      joints. New sequences and experience with MRI has lead to increased sensitivity
      and specificity of internal joint lesions. For the first time, contusions of the
      subchondral bone which are prognostically significant for the developing of
      chondral lesions can be identified. To date, no other tests are available to
      identify such lesions. This review article outlines the current value of MRI for
      evaluating post-traumatic knee joint injuries.

PMID- 7740115
TI  - [Osteochondral lesions].
AB  - MRI has demonstrated high diagnostic value in the assessment of musculoskeletal
      disease. Pathological joint changes, especially in the osteochondral region, are
      an important orthopedic problem because the signs and symptoms are vague and
      unspecific. Therefore, in early disease their extent and severity are difficult
      to ascertain clinically. Early diagnosis and exact staging are recommended for
      sufficient therapeutic management. MR imaging has proved to be the method of
      choice in the evaluation of osteochondral lesions and helps to prevent late-stage
      disease and joint damage.

PMID- 7740116
TI  - [Functional MRI of the femoropatellar joint].
AB  - Conventional X-ray examinations of the patellofemoral joint in 30 degrees, 60
      degrees and 90 degrees of knee flexion demonstrate the position of the patella.
      On the other hand, they have been shown to be insufficient for the diagnosis of
      patellofemoral maltracking in the critical range between 30 degrees of flexion
      and full extension. Motion-triggered and ultrafast MRI offer new possibilities
      for functional diagnosis of the patello-femoral joint under active knee motion.
      Functional MRI of the patellofemoral joint is suggested as an alternative to
      arthroscopy, particularly in patients with anterior knee pain or suspected
      patellar maltracking.

PMID- 7740117
TI  - [Ultrasound diagnosis of the popliteal fossa].
AB  - Sonography of the knee is a well-established method for the diagnosis of palpable
      tumors. However, evaluation of the menisci, cruciate ligaments, and hyaline
      cartilage is controversial. Despite the variable echogenicity and extension of
      different diseases, many distinct sonographic signs are different in cysts, solid
      neoplasms, and vascular diseases. The investigator must be familiar with various
      patterns of popliteal cyst formation: crescent-shaped, cross-shaped, slitlike,
      and grape-like cysts. Because of diagnostic and economic reasons the following
      concept should provide guidance when diagnosing lesions of the popliteal fossa:
      the first step of diagnostic imaging should include plain film radiography and
      sonography. In a second step MRI and/or arthroscopy should be performed.

PMID- 7740118
TI  - [Turbo-spin-echo MR imaging of the brain at 0.5 T].
AB  - Turbo-spin-echo (TSE) imaging is a fast technique, which provides true spin-echo
      contrast in a definitely shorter scan time than conventional spin-echo (SE).
      Clinical studies at 1.5 T show that TSE is a valuable alternative to SE and will
      ultimately replace time-consuming T2-weighted SE imaging for examinations of the
      brain and brainstem. Besides the reduction of scan time, TSE is less sensitive to
      motion artefacts. A slight decrease of susceptibility effects of 1.5 T can be a
      disadvantage in the detection of old haemorrhagic lesions and calcifications. In
      these cases the gradient-echo sequence will remain the most sensitive. TSE allows
      a greater flexibility of examination strategies, including several orientations,
      strongly T2-weighted images and high spatial resolution (HR) MRI. HR MRI using
      thin slices (1-3 mm), a small field of view and a 512 image matrix yields
      detailed information about small anatomical regions (e.g. the pituitary fossa,
      cavernous sinus, internal auditory canal and brainstem) and permits the
      delineation of specific cranial nerves. In this study TSE was utilized at 0.5 T
      field strength in order to assess whether the advantages of TSE hold for midfield
      systems. Preliminary results in imaging of the brain and brainstem are very
      promising.

PMID- 7740119
TI  - [Worm-like calcinosis of the left middle abdomen. Dislocated incrustation of the
      proximal catheter end].

PMID- 7740120
TI  - [Anatomy and biomechanics of the knee joint].
AB  - The morphology of the components of the knee joint is reviewed, with particular
      reference to the ever-widening range of technical representation offered by
      modern imaging procedures. The morphological parameters of cartilage thickness,
      thickness of the subchondral zone of mineralization and subchondral X-ray density
      (assessed by CT osteoabsorptiometry) are depicted, and the various parts of the
      capsular ligamentous apparatus are described, with particular attention to the
      cruciate ligaments and menisci. The periarticular topography is also dealt with
      briefly. An attempt is made to elucidate with diagrams the essential basis of the
      static stress acting on the joint. The kinematics and dynamics are examined with
      particular reference to new theories about control of the position of the joint
      as a result of sensory functioning of the cruciate ligaments.

PMID- 7740121
TI  - [Knee joint cartilage in magnetic resonance tomography. MR chondrovolumetry (MR
      CVM) using fat-suppressed FLASH 3D sequence].
AB  - The objective of this study was to optimize the demonstration of articular
      cartilage with magnetic resonance tomography (MRT) and to assess its accuracy in
      determining the articular cartilage volume of the knee joint. METHODS: A fat
      suppressed FLASH-3D sequence was optimized on healthy volunteers. A fresh
      cardaveric knee joint was removed from a 82-year-old man and immediately imaged
      without being frozen or fixed. MRT was carried out at 1.5 T and 25 mT/m (Vision,
      Siemens, Erlangen, Germany) with a conventional CP knee coil. Sagittal and
      transverse sections were acquired perpendicular to the articular surfaces, and
      then, parallel to these imaging planes, anatomical sections were obtained with a
      diamond band saw. The volumes of the patellar, tibial and femoral cartilages were
      determined from both the images and the sections, using an image analysing
      system. RESULTS: Signal intensities and contrast-to-noise ratios depend on the
      parameters used. The highest contrast between the cartilage and the periarticular
      tissues was obtained at a flip angle of 30 degrees (TR = 60 ms, TE = 11 ms).
      However, a flip angle of 60 degrees was judged to provide optimal subjective
      image quality. Using these parameters, the deviations between the radiological
      and the anatomical cartilage volumes were -4.7% in the patella, -3.1% in the
      tibial plateau and -4.2% in the femur. CONCLUSIONS: The volumes of the knee-joint
      cartilages may be accurately determined with MRT if an appropriate pulse sequence
      is chosen. From a clinical point of view the differences between MR images and
      anatomical sections can be considered negligible. These differences may be
      explained on the basis that MRT delineates uncalcified cartilage only and that
      the calcified layer is demonstrated as part of the subchondral bone plate.
      However, close correlation of the thicknesses of the uncalcified and the
      calcified layer has been reported in the literature, so the relative distribution
      of articular cartilage should be accurately reflected in MR images.

PMID- 7740122
TI  - [Diagnosis of changes in the knee joint of high performance athletes].
AB  - Sport-associated knee-joint alterations are frequent. A correct and rapid
      differentiation between traumatic lesions, chronic degenerative changes, and
      adaptive processes is important with regard to therapy as well as training and
      competitive planning for athletes. After the case history and physical
      examination, X-ray images are an absolute necessity for more in-depth diagnostic
      procedures. Depending on the clinical symptoms, partial aspects of the knee-joint
      can be visualized by sonography as well as by conventional tomography and
      computed tomography. If, however, a comprehensive evaluation of all knee-joint
      structures is needed, magnetic resonance imaging of the knee-joint should be
      performed. As a rapid, noninvasive procedure with high diagnostic reliability for
      all essential knee-joint structures only magnetic resonance imaging presently
      fulfills the specific demands placed on a modern diagnostic procedure by doctors
      working in sports-medicine.

PMID- 7740123
TI  - Blocking in human electrodermal conditioning.
AB  - Associative blocking in human conditioning was investigated using electrodermal
      and self-reported US expectancy measures. Previous null results using a design
      reported by Lovibond, Siddle, and Bond (1988) suggested that a clearly demarcated
      phase structure and visual cues with semantic content may have distracted
      attention from the experimental contingencies. Therefore the current experiment
      intermixed pre-training and compound training trials and masked the transition to
      the test phase to remove or reduce phase boundaries. Simple coloured squares were
      used as CSs to reduce semantic content. A significant blocking effect was
      observed on both the expectancy measure and on the electrodermal measure. Both
      results were due to improved transfer of conditioning to the target CS in the
      overshadowing control group in comparison to previous experiments. The results
      were interpreted as providing evidence that previous null results were due to
      failure of transfer of learning across clearly distinct phases. There was no
      evidence of a dissociation between the electrodermal and self-report measures.
      Theoretical and procedural implications for human Pavlovian conditioning are
      discussed.

PMID- 7740124
TI  - Enhanced latent inhibition following compound pre-exposure.
AB  - The influence of non-reinforced exposure to compound stimuli on subsequent
      appetitive classical conditioning was examined in five experiments with rats as
      the subjects. Non-reinforced exposure to a visual stimulus retarded subsequent
      acquisition of conditioned responding relative to a non-pre-exposed condition
      (latent inhibition). If the target stimulus was pre-exposed in compound with a
      second (non-target) stimulus, then latent inhibition was abolished. Exposure to
      the non-target stimulus prior to compound exposure had varying effects on
      subsequent conditioning to the target: 40 exposures to the non-target stimulus
      resulted in latent inhibition to the target stimulus that was comparable in
      magnitude to that observed when the target stimulus was exposed in isolation; 120
      exposures to the non-target stimulus enhanced latent inhibition to the target
      stimulus.

PMID- 7740125
TI  - Stimulus salience and negative patterning.
AB  - Rats in Experiment 1 received a negative patterning discrimination in which food
      was delivered after either of two auditory stimuli when they were presented
      individually, but not when they were presented in compound. The stimuli were of
      different intensity. The discrimination between the compound and the stimulus of
      lower intensity was acquired more readily than was the discrimination between the
      compound and the more intense stimulus. A similar pattern of results was found in
      the remaining two experiments, which also employed a negative patterning
      discrimination, but either with stimuli from different modalities (Experiment 2)
      or with pigeons rather than rats (Experiment 3). The results were predicted more
      readily by a configural than by an elemental theory of conditioning.

PMID- 7740126
TI  - Effects of sexual conditioning of devaluing the US through satiation.
AB  - Male Japanese quail were conditioned to approach a visual CS that predicted an
      opportunity to copulate with a female quail. Subsequently the subjects were
      tested in both non-reinforced and reinforced test trials while sexually satiated
      and sexually deprived. In the satiation condition the sexual US was devalued by
      allowing the male subjects to copulate repeatedly with female birds just prior to
      testing. The subjects displayed significantly less approach to the CS when
      sexually satiated than when sexually deprived. These results are compatible with
      a mechanism in which performance of Pavlovian sexual approach conditioning is
      mediated by activation of a memorial representation of the US.

PMID- 7740127
TI  - A simple data transformation for estimating benchmark doses in developmental
      toxicity experiments.
AB  - Developmental anomalies induced by toxic chemicals may be identified using
      laboratory experiments with rats, mice or rabbits. Multinomial responses of
      fetuses from the same mother are often positively correlated, resulting in
      overdispersion relative to multinomial variation. In this article, a simple data
      transformation based on the concept of generalized design effects due to Rao
      Scott is proposed for dose-response modeling of developmental toxicity. After
      scaling the original multinomial data using the average design effect, standard
      methods for analysis of uncorrelated multinomial data can be applied. Benchmark
      doses derived using this approach are comparable to those obtained using
      generalized estimating equations with an extended Dirichlet-trinomial covariance
      function to describe the dispersion of the original data. This empirical
      agreement, coupled with a large sample theoretical justification of the Rao-Scott
      transformation, confirms the applicability of the statistical methods proposed in
      this article for developmental toxicity risk assessment.

PMID- 7740128
TI  - [Treatment of osteomyelitis by local antibiotics using a portable electronic
      micropump].
AB  - INTRODUCTION: Systemic administration of antibiotics in osteoarticular infections
      is characterized by: 1) systemic side effects: 2) questionable penetration of the
      antibiotic into the infected and ischaemic areas: 3) mandatory hospitalization
      for prolonged administration of antibiotics. Aware of these difficulties,
      orthopedic surgeons have long been seeking an effective method of local
      antibiotic administration. The authors report their original experience with the
      use of an external, portable electronic micro pump for continuous local delivery
      of antibiotics in conjunction with surgical debridement, in the treatment of
      osteomyelitis. MATERIALS AND METHODS: Ten patients with active chronic
      osteomyelitis, were treated with surgical debridement and local antibiotic
      therapy. On the basis of the sensitivity disk findings, vancomycin or amikacin
      was delivered locally through an external portable, electronically programmable
      micro pump. To connect the pump with the infected site Groshong or Buchwald
      catheters were employed. The reservoir of the pump was refilled every 10-15 days.
      RESULTS: The duration of symptoms ranged from six months to fifteen years. All
      patients had undergone at least one previous unsuccessful treatment consisting of
      surgical debridement and/or prolonged intravenous antibiotic therapy. The
      duration of the infusion therapy ranged from 80 to 207 days (mean 109 +/- 37.7).
      At 33.7 +/- 5.6 months follow-up (range twenty-one to thirty-nine months) eight
      patients out of nine (one patient was lost to follow-up), showed no recurrence of
      the infection as manifested by clinical, laboratory and imaging data. Serum
      vancomycin and amikacin levels, measured at different intervals from the
      beginning of therapy, were always well below the recommended through levels for
      systemic infusion. There were no side effects linked to the prolonged
      administration of antibiotics, no technical complications connected with the
      implantation and removal of the catheter and no infections of inflammation of
      subcutaneous tissue where the catheter had been placed or of the skin around the
      catheter. DISCUSSION: The use of subcutaneous, totally implantable infusion drugs
      pumps, as proposed by Clayton, Perry and co-workers (1986) allows: 1) to maintain
      adequate local levels of a wide variety of antibiotics for a long period of time,
      avoiding systemic toxicity; 2) to stop the infusion in case of adverse reactions
      (allergic response): 3) to administer the treatment on an outpatient basis. Our
      original proposal of an externally portable micro pump adds the following
      advantages: 1) it is less invasive: 2) no risk of infection of the subcutaneous
      pocket where the pump is lodged: 3) better stability of the antibiotic, being at
      ambient temperature instead of at nearly 30 degrees C: 4) much lower cost, the
      external pump being less expensive than an implantable one and is reusable.
      CONCLUSION: Our experience shows: 1) the simplicity and limited invasiveness of
      this technique, which, without excluding other forms of therapy, allows to
      deliver antibiotics in the infected focus for months; 2) the absence of side
      effects and technical complications; 3) the good quality of life of the patients
      during the treatment; 4) the low cost for the health care system, since the
      patients are followed-up and the reservoirs refilled on an out-patient basis.

PMID- 7740129
TI  - [The spinal accessory nerve (n. accessorius) I: anatomical study].
AB  - INTRODUCTION: In order to increase knowledge of the spinal accessory nerve
      concerning its situation, trajectory and terminal branches and also the
      connections with the cervical plexus, the authors report an anatomical study
      based on 11 dissections of the trapezius muscle mode of innervation and the
      connections between the accessory nerve, the sternocleidomastoid and trapezius
      muscles. DISCUSSION: The accessory nerve is a muscular nerve and supplies the
      main innervation to the trapezius muscle especially for the superior and middle
      sections. There is a clear participation of the cervical plexus either through
      the trapezius muscle by nerve anastomosis behind the trapezius or directly
      especially in the distal portion. CONCLUSION: This anatomical study allows a
      better understanding of the clinical aspects and the indications of nerve
      repairs.

PMID- 7740130
TI  - [Traumatic lesions of the spinal accessory nerve. II: clinical study and results
      of a series of 25 cases].
AB  - INTRODUCTION: Trapezius muscle paralysis after accessory nerve injury was mostly
      seen after a so called minor surgery of the neck: 17 lesions among 25 appeared
      after the excision of a cervical cyst or a small benign tumor. This notion should
      be remembered because the prevention of this paralysis is easy. MATERIAL AND
      METHODS: In the established lesion, the repair is to be done as soon as possible.
      The authors report a retrospective study of 25 cases of traumatic accessory nerve
      injury, followed from 1983 and 1992. A nerve repair was done in 15 cases. It
      consisted in an average 5 centimeters graft in 10 cases, an intramuscular
      neurotization in 4 cases, a direct suture in 1 case, and a neurolysis in 6 cases.
      A palliative treatment was suggested in 4 cases. RESULTS: The mean follow up was
      15 months (range 6 to 57 months) and 22 operated cases had more than a 1 year
      follow up. We observed 10 good results for 10 grafts, 1 good result after 1
      direct suture; the 4 neurotisations has 3 good results and 1 average result; the
      6 neurolysis had 1 very good, 4 good and 1 poor results and in one case there was
      no possibility of repair. DISCUSSION AND CONCLUSION: The authors underline the
      good results after nerve repair following a lesion near from the paralysed muscle
      and also the need for prevention.

PMID- 7740131
TI  - [Clinical and radiographic results of a continuous series of 124 type Ceraver
      Osteal hip prostheses with a 9-year survival analysis].
AB  - INTRODUCTION: Since 1979, we have been using a model of cemented total hip
      arthroplasty (THA) with a titanium femoral stem, a 32 mm femoral head, and for
      some cases an alumina on alumina browing combination. We tried to appreciate the
      results of these different modifications with a sufficient follow-up. MATERIALS
      AND METHODS: Among the 124 THA, 63 sockets were made of alumina, 61 of
      polyethylen, 22 patients had deceased and 23 were lost for follow-up before seven
      years, we studied 72 THA followed between 7 and 9 years up. The cementing
      technique was not modified. The clinical evaluation was done using the Merle
      d'Aubigne-Postel hip rating scale the radiographic analysis was conducted for 79
      hips. RESULTS: After 9 years 8 cups had been removed for loosening, 2 hips were
      operated for infection, the global survivorship without a new operation was then
      88.73 per cent. Among all hips, 80 per cent were clinically rated as "fair" or
      better. We noticed 8 migrations among the alumina cups and 6 among those made of
      polyethylene. Among the 31 polyethylene cups, there were 25 lucencies between
      bone and cement (18 < 1 mm). Among the 48 alumina cups there were 22 lucencies
      just between bone and cement and 21 between cup and cement and also between bone
      and cement (double lucencie). The lucencies between cup and cement were more
      often in the lower third of the cup and 7 of the 8 migrations had double
      lucencies. Forty-nine percent of the femoral stems had lucencies, 40 per cent in
      the proximal zones. But there was just one femoral subsidence associated with the
      lowest distal femoral filling. So just considering the femoral subsidence the
      survivorship was 98.79 per cent. DISCUSSION: The clinical results of this series
      were as good as the more recent series. Because of the difference of
      radiographical aspect between the polyethylene and alumina cups, the high rate of
      lucencies and migration could have been interpreted as two different mechanisms.
      For polyethylene cups, the 32 mm femoral head is frequently associated with this
      complication, as it was already described in other series. For the alumina, the
      difference of elasticity between bone and cement should have been the principal
      responsible. As we considered just the migration of the stem, and although the
      cementing technique was simple, our rate of femoral loosening was as low as in
      the more recent series. The frequent proximal lucencies should may be not be
      considered as loosening but as consequence of the elasticity of titanium. The
      distal fixation obtained by a good distal femoral filling seemed to be the more
      important point. CONCLUSION: To reduce the acetabular loosening rate we use now a
      head of 28 mm for the metal on polyethylene combination, the alumina cup has been
      abandoned and the alumina on polyethylene combination should still be assessed.
      The encouraging femoral results, due to the good femoral filling and to the
      titanium elasticity needs to be confirmed after a longer follow-up.

PMID- 7740132
TI  - [Butel's isoelastic hip prosthesis. A limited prospective study].
AB  - INTRODUCTION: A limited prospective study was undertaken at the Centre
      Hospitalier de l'Universite Laval to assess the outcome of 21 isoelastic
      prostheses described by Butel. MATERIAL AND METHODS: The femoral component
      consisted of a one-piece forged stainless steel stem with four metallic rods
      ranging in diameter from 11 to 18 mm, in 1 mm increments. The two lateral and
      medial rods, 20 cm in length, were linked distally. The 2 mm gap between the
      medial and lateral rods was obliterated at insertion, allowing the component to
      be firmly seated in the femoral canal. Twenty-one Butel isoelastic prostheses
      were inserted in 20 patients (14 men and 6 women with an average age of 51
      years). The preoperative diagnosis was aseptic total hip prosthetic loosening in
      three cases, rheumatoid arthritis in five cases, avascular necrosis in six cases
      and degenerative arthritis in six cases. A standard postero-lateral approach was
      used in all cases. Postoperatively, the patients were mobilized immediately, with
      partial weight bearing on the affected side for six weeks. RESULTS: Follow-up
      ranged from 24 to 34 months with an average of 28 months. One patient, who
      developed a late infection, was excluded from the study. Nineteen patients with
      20 prostheses were reviewed clinically and roentgenographically by independent
      observers in the absence of the senior author. Clinically, the patients rated 11
      to 58 on the preoperative Harris scale with an average of 34 while they rated 39
      to 96 postoperatively with an average of 67. Eight patients were below 70 on the
      Harris scale postoperatively and were rated unsatisfactory. Eleven patients
      complained of postoperative thigh pain which was still present in three patients
      after two years. None complained of pain related to the acetabular component. On
      roentgenograms, prosthetic seating seemed to be inadequate in 14 cases but with
      good clinical results in 9 cases. Seating seemed to be adequate in six cases but
      with an unsatisfactory outcome in three cases. DISCUSSION: The concept of
      isoelasticity is that the implant and bone should deform as one unit. However,
      clinical results of an implant must be validated by investigators who are not
      developers of their own implant. The results in this series do not corroborate
      with those reported by Butel. A number of technical problems occurring at or
      after surgery precluded the safety, efficacy and durability of the surgical
      procedure and its successful outcome. A substantial incidence of thigh pain was
      found in this series. This has also been noted by a variety of authors using
      femoral designs with a large intramedullary rod which has less torsional
      stability than a flat wedge shaped femoral implant. CONCLUSION: The isoelastic
      prosthesis used in this series did not fulfill the expectations and was
      considered marginal in regards to quality and efficiency.

PMID- 7740133
TI  - [Neonatal screening for congenital hip dislocation. Indication of ultrasonography
      from a systematic study correlating clinical findings and ultrasonography].
AB  - INTRODUCTION: The aim of our study was to verify the correlation between clinical
      and sonographic screening for CDH. MATERIALS AND METHODS: Clinical and
      sonographic screening was carried out in 1000 newborns (2000 hips) during the
      first week of life. Anamnestic risk factors were evaluated and clinical
      examination was performed using the BARLOW, Le DAMANY and ORTOLANI maneuvers. We
      also took into account a possible limitation of abduction due to adductor
      hypertonia and the presence of a hip crepitation. All hips were evaluated by
      ultrasound examination using Graf's morphologic method. We considered as
      clinically pathological the positive BARLOW, Le DAMANY and ORTOLANI hips and
      "doubtful" the stable hips having "crepitation" or "hypertonia of the adductors".
      The hips considered pathological with the ultrasound were the hips 2c, 3a and 3b
      according to GRAF. RESULTS: 1) Hips clinically pathological (BARLOW, Le DAMANY
      and ORTOLANI): 150 (7.5 per cent). 2) The clinically stable hips but "doubtful":-
      crepitation: 105 (5.25 per cent); adductor hypertonia: 86 (4.3 per cent), total
      191 (9.55 per cent). 3) Hips clinically normal but with at least anamnestic risk
      factor: 198 (9.9 per cent); 4) Hips clinically normal but without anamnestic risk
      factor: 1461 (73.05 per cent). 5) Hips echographically pathological, that is 2c,
      3a and 3b according to Graf: 124 (6.2%) and particularly 2c: 61 (3.05 per cent),
      3a: 61 (3.05 per cent) and 3b: 2 (0.1 per cent). DISCUSSION: 1) In the clinically
      pathological hips (BARLOW positive) 36 were echographically pathological with a
      clinical-sonographic correlation of 28.3 per cent (36 out of 127); all the
      ORTOLANI positive hips, were echographically pathological (100 per cent (23 out
      of 23)). In doubtful hips, sonograms were pathological in 17 of 105 hips with
      "crepitation" (0.85 per cent) and in 13 of 86 hips with "adductor hypertonia"
      (0.65 per cent). 2) The clinically and echographically pathological hips at
      birth, that is 2c, 3a and 3b, must be followed for months. At follow up they
      showed in almost all the cases an evolution towards normality. It is, therefore,
      indicated to repeat the clinical and sonographic examination in the first month,
      before undertaking any kind of treatment. 3) Finally, 12 hips, 0.6 per cent,
      presenting pathological sonographic type 2c and 3a, were found clinically normal.
      Nevertheless, almost all of these hips evolved normally. From this study only
      0.05 per cent of clinically normal hips presented, later, a dysplasia of the
      acetabulum. Analysis of the results clearly showed that ultrasound examination
      may be an excellent help to clinical examination which, if well performed, has
      top priority for early diagnosis of C.D.H. CONCLUSION: The clinical examination,
      carefully performed in the first days of life, has priority because it allows
      discovering a pathological hip or a hip at risk. The sonographic examination is a
      useful image complementing the clinical examination because it allows
      confirmation of the diagnosis and follow up of the morphologic evolution of the
      hip with an inoffensive method and it can give indications for possible
      treatment. From our study we may conclude that at birth a clinical screening is
      preferable and that the ultrasound study is to be reserved for pathological,
      doubtful or at risk hips.

PMID- 7740134
TI  - [Treatment of limb deformities by the Ilizarov method].
AB  - INTRODUCTION: The numerous possibilities for adapting the Ilizarov apparatus
      allows the progressive correction of complex angular deviations, for which flat
      apparatus are sometimes difficult to adapt and this report describes our
      experience using the Ilizarov apparatus to treat axial limb deformities. MATERIAL
      AND METHODS: A total of 48 patients (22 girls and 26 boys aged between 2 and 18
      years-old) suffering from 58 angular deformities were treated with an Ilizarov
      device. 40 of the deformities involved bones: 22 tibias, 13 femurs and 6 radius.
      The remaining 18 deformities involved joints, (17 knees and 1 elbow), 12 were
      total ankylosis and 6 were flexion contractures. 31 of the cases involved an
      isolated deformity (16 bones and 16 joints) and 27 were associated with other
      orthopedic problems. The cause of the deformities were either malformation or
      infection in most cases. In 39 cases the angular deformities were deviations in a
      single plane: 13 in two planes and 6 deformities were complex, involving
      deviation in all three planes. Correction was progressive in 49 cases and
      immediate in 9 cases. Unequal limb length was treated in 21 cases: 19 of these
      were caused by bone deformity. The apparatus should cover the entire bone segment
      to be corrected, from metaphysis to metaphysis. When the deformity is close to a
      joint, the joint should be bridged so as to stabilize the brace. The fastening of
      the sides of the deformity involves a maximum of three pins in two different
      planes. The apparatus must be absolutely rigid so as to avoid any lateral
      slipping or any movement of the rings relative to the segments of the limbs. The
      two parts of the apparatus fixed on either side of the deformity should be linked
      by two groups of three threaded rods with articulations at the ends. When the
      correction is in a single plane, it is effected around the axis formed by two
      threaded rods at the point of the deformity. When the deformity is major, 90
      degrees or more, the rings tend to shift under the strain, and this leads to a
      loss of correction and cutaneous problems on the concave face. This may be
      avoided by fixing threaded rods to the ring, perpendicular to the plane of the
      deformity. For knee flexion contractures, the rods should be connected to the
      ring where it crosses the frontal plane passing through the femoral diaphysis.
      RESULTS: 48 angular deviations were completely corrected. In 10 cases the
      deformity persisted, but was less than 20 degrees. The deformity reoccurred in 6
      of the children: in 3 cases due to the persistence of muscular imbalance, in two
      cases by assymetric growth, in the other case by plastic deformation on the
      insufficiently mineralized regenerated bone tissue formed during lengthening. In
      one case, the common, motor and sensor peroneal nerve was paralyzed, complicating
      the correction of an anterior dislocation of the knee. The paralysis occurred at
      the end of the correction and recovery began after 6 months. One 10 year old
      child, suffering from nail patela syndrome, was left with a completely
      immobilized elbow after treatment of a webbed, 100 degrees flexion contracture. A
      total of 9 epiphyseal separations (Salter I type) occurred during the correction
      of severe deformities, with little or no displacement, all occurred around the
      knee. These epiphyseal separations did not interfere with the treatment of the
      angular deviations in three cases, however, advantage was taken of these events
      to effect the intended lengthening of the bone. DISCUSSION: The Ilizarov method
      for correcting joint ankylosis is difficult to perform, and depends on a detailed
      knowledge of the apparatus and braceing system, and requires rigourous
      installation of the pins, ring, joints and rods. Whatever the position of the two
      rings in relation to each other, it is always possible to link them by a system
      which can be adjusted. This is not possible with other external braces which have
      only a single plane.

PMID- 7740135
TI  - [Osteochondroma of the clavicle and pain syndrome of the shoulder. Apropos of a
      case. Review of the literature].
AB  - INTRODUCTION: Osteochondroma, a frequent benign tumor of the bone, is in most
      cases asymptomatic. Localization in the clavicle is extremely rare. The authors
      report an isolated case occurring in the coraco-clavicular area responsible for a
      painful shoulder syndrome evoking rotator cuff tendinitis. METHODS: A 47 years
      female patient consulted for painful shoulder syndrome. Pain occurred following
      an effort and at night. On clinical examination, the area around the coracoid
      process was tender as was the supraspinatus fossa. Passive anterior elevation of
      the shoulder was limited to 150 degrees. She had a positive Job's sign as well as
      a painful << Gross armtest >>. Initial Radiological assessment showed no
      anomalies. Arthrographic CT scan revealed an expansive process compatible with
      osteochondroma. The lesion was in contact with the supraspinatus muscles and the
      coracoid process. Extraperiosteal resection was performed through a delto
      pectoral approach. Recovery of a painless mobile joint was rapid. DISCUSSION:
      Clavicular embryology is not yet well understood. The appearance of an exostosis
      at this localization seems to confirm that the clavicular cartilage behaves as an
      epiphyseal bone plate. The exostosis, which has a congenital origin, can appear,
      when it reaches a certain size or when it mechanically interferes with
      surrounding muscles and tendons. In our observation, the lesion led to irritation
      of the supraspinatus muscle leading to tendinitis. Diagnosis is usually made on
      standard roentgenographic evaluation. CT scan and MRI show a cartilaginous
      coating which should not exceed 10 mm in the case of a benign tumor. There exists
      a possibility of sarcomatous degeneration, but this is rare on the peripheral
      skeleton. Treatment should be performed by complete extraperiosteal resection of
      the exostosis along with its perichondral cover. CONCLUSION: Clavicular
      localization of an osteochondroma is very rare. This case report illustrates the
      possibility of a painful shoulder syndrome associated with this lesion. This
      report also seems to suggest the hypothesis that the cartilage at this level
      behaves as an epiphyseal bone plate.

PMID- 7740136
TI  - [Proximal epiphyseal separation of the femur in the newborn: early ultrasonic
      diagnosis].
AB  - INTRODUCTION: Obstetrical separation of the proximal femoral epiphysis at birth
      is rare. Most of these fractures are associated with complicated deliveries.
      MATERIAL AND METHODS: Our patient was admitted on the first day after birth. He
      was born by caesarean section due to a breech presentation. The clinical
      examination revealed << pseudoparalysis >> of the left lower extremity.
      Laboratory studies were within normal limits. RESULTS: Roetgenograms showed a
      superolateral displacement of the proximal femur with normal acetabular
      development. An ultrasound examination revealed a normal position for the left
      femoral head within the acetabulum and no joint effusion. This excluded the
      possible diagnosis of septic or congenital dislocation of the hip and confirmed
      the diagnosis of traumatic epiphyseal separation. CONCLUSION: Recognition of this
      rare injury by using ultrasound may allow early diagnosis and treatment, thus
      preventing permanent deformities.

PMID- 7740137
TI  - [Arthroscopy of the ankle: a new of postero-internal point of entry].
AB  - INTRODUCTION: The development of the indications in the arthroscopic surgery of
      the ankle and the narrowness of this joint impose perfectly adapted portals.
      Several posterior portals which allow to access to the postero medial corner of
      the joint have been already described, but are not satisfying. We describe, here,
      a new postero-medial portal which allows a safe and easy access to the posterior
      part of the joint. METHODS: The arthroscopy is performed with a standard
      arthroscope (30 degrees, 4.5 mm in diameter) and a lateral ankle distractor. The
      landmark for this portal is the posterior crest of the medial malleolus. Above
      the posterior tip of the medial malleolus, this crest is directed up and back,
      then its direction becomes strictly vertical. The new portal is situated there, 5
      millimeters behind the crest (generally 2 centimeters above the posterior tip of
      the medial malleolus). A needle visualized by the anterior portal is helpful to
      show the right direction for the portal. After skin incision, a forceps is used
      to widen the portal. Then the instruments or the arthroscope can be introduced.
      Posterior tibial artery and nerve are protected by the tendons of tibialis
      posterior and flexor digitorum longus. MATERIAL: We have used this portal
      (instrumentation and arthroscope) in four patients (3 osteochondritis dissecans
      of the medial part of the talus, 1 loose body) without problem. RESULTS: This
      portal is safe; it does not intersect the direction of posterior tibial artery
      and nerve as in the postero-medial portal described by Parisien and avoids in
      most cases the approach described by Guhl. DISCUSSION: Because the medial
      malleolus is more anterior than the lateral malleolus, it allows a larger
      approach to the posterior part of the joint than the postero-lateral portal. We
      recommend it for the arthroscopic treatment of all the lesions of the postero
      medial part of the joint.

PMID- 7740138
TI  - [A new technique of osteotomy for femoral varisation in the management of hip
      dislocation and paralytic subluxation of the hip].
AB  - PURPOSE OF THE STUDY: Severe valgus deformity of the upper femur is a frequent
      feature of the unstable paralytic hip. Thus, the insertion of the osteosynthesis
      material during a varization osteotomy can be technical demanding. Risks and
      benefits of a modified femoral varization osteotomy were evaluated in a
      retrospective follow-up study. MATERIAL: 53 paralytic hips (33 patients) have
      been operated from September 1989 to april 1993. Mean age at surgery was 6 years.
      The etiologies were Spinal Amyotrophy in 12 hips, Cerebral Palsy in 31 hips and
      miscellaneous neurologic diseases in 10 hips. The average neck-shaft angle before
      surgery was 162 degrees. The mean Reimers' Index was 58 per cent. METHODS: The
      upper femoral shaft was exposed by subperiosteal dissection in a circumferential
      manner. An intertrochanteric osteotomy was carried out. The direction of the
      femoral neck was identified. An AO 100 degree blade plate was then introduced
      under direct visual control through the cancellous osteotomy surface of the
      proximal fragment. Radiological and clinical outcome were assessed at last follow
      up. Mean follow-up was 16 months. RESULTS: Solid fusion was obtained in all
      patients. The mean postoperative neck-shaft angle was 104 degrees. The mean
      Reimers' Index was 17 per cent at last follow-up. Two infections were noted.
      Voluminous calcifications under the femoral neck have been observed in 6 cases.
      Recurrence of the valgus deformity was noted in 9 hips at last follow-up.
      DISCUSSION: This simplified varization technique permits a large amount of
      varization. The medialization diminishes the problem of protruding hardware. The
      complications rate appears to be low without any femoral head necrosis in this
      series despite subperiosteal dissection of the femoral neck. CONCLUSION: The
      authors think that this modified varization technique may deserve consideration
      in the treatment of the unstable paralytic hip.

PMID- 7740139
TI  - [Apropos of: "Closed medullary nailing of complex fractures of the femoral
      diaphysis in adults. Apropos of 68 cases"].

PMID- 7740140
TI  - [Apropos of: "Acetabulum anteversion in congenital luxation of the hip"].

PMID- 7740142
TI  - [Early surgical treatment of symptomatic hypertrophic obstructive myocardiopathy.
      Arguments in favor].

PMID- 7740141
TI  - [Which patients with heart valve diseases require invasive evaluation?].

PMID- 7740143
TI  - [Early surgical treatment of symptomatic hypertrophic obstructive myocardiopathy.
      Arguments against].

PMID- 7740144
TI  - [Accuracy and clinical applicability of the echocardiographic automated
      endocardial boundary detection system: correlation and bias analysis].
AB  - INTRODUCTION AND OBJECTIVES: Automated edge detection of endocardial borders is a
      new echo system that permits on-line delineation and tracking of blood-tissue
      interface and offers promise for measuring cyclic changes in cavity area and the
      assessment of left ventricular function on-line. Its accuracy has only been
      analyzed by linear regression and its applicability in unselected patients is not
      clearly established. METHODS: We analyzed the accuracy and clinical applicability
      of the system in 150 patients. Its accuracy was assessed not only by linear
      regression but also by bias analysis by comparing the results of the system with
      those obtained by manual tracing from parasternal short-axis and apical 4 chamber
      views. RESULTS: We obtained satisfactory studies with this system in at least one
      of the two echo views in 66% of patients: 47% from 4-chambers view, 43% from
      parasternal short-axis view and 24.6% from both echo views. A visual
      semiquantitative assessment of left ventricular function could be performed in
      88.6% of patients (p < 0.001). On-line and hand-traced left ventricular areas
      there well correlated, but fractional area change values from both methods
      correlated less closely. 95% limits of agreement between both methods were: 2.8
      +/- 5.5 cm2 (end-diastolic area), 1 +/- 4.4 cm2 (end-systolic area) and 1.2 +/-
      23% (fractional area change) in short-axis parasternal view; in apical 4-chambers
      view these limits were: 1.16 +/- 6.4 cm2,--1.1 +/- 6 cm2 and 7.3 +/- 16%,
      respectively. CONCLUSIONS: Although the correlations between left ventricular
      areas from both methods were close the limits of agreement exceeded our
      acceptable range of reproducibility. Fractional area change showed only moderate
      correlations and a lack of agreement with off-line method. Poor image quality of
      the conventional echo still limits the clinical applicability of the current
      automated edge detection system.

PMID- 7740145
TI  - [Analysis of hemodynamics costs. A multicenter study based on consumed
      resources].
AB  - INTRODUCTION AND OBJECTIVES: The main objective of this study is to know actual
      hemodynamic explorations costs in Spain, not only direct but total imputation
      costs, through a registration of duration, resources and disposables used in this
      minimally invasive exploration. Also to explore the variability in costs and
      consumptions between hospitals with similar technology in catheterization
      practice. METHODS: The effective duration, supplies consumptions and manpower
      resources utilized in 762 diagnostic catheterization, 217 therapeutic
      coronarographies, and 32 Inoue mitral valvotomies have been registered and
      analyzed in four public Spanish hospitals. The direct costs have been calculated
      through purchase and repair bills and officials wages. The indirect ones through
      repercussion judgements, and the amortization on a ten years imputation process.
      RESULTS: The consumption, duration and manpower data are shown with media and
      standard deviations. Final costs are: 106,879 pesetas for a diagnostic
      catheterization, 545,614 pesetas for a therapeutic coronarography, and 556,315
      pesetas for a mitral Inoue valvotomy. Significative differences have been
      demonstrated between hospitals affecting the majority of consumption and manpower
      variables. There are also wide differences on indirect costs, amortization and
      maintenance costs. CONCLUSIONS: The catheterization costs are high in Spain
      mainly due to disposable material costs in spite of low manpower costs in public
      hospitals. The indirect administration costs are of relative importance in
      diagnostic catheterization, but in the therapeutic ones the only important
      payment are the disposable material costs who get the 85% of total cost. The
      differences between hospitals in durations and consumptions show the need to
      improve medical protocols. The differences in indirect costs reflect different
      steps in implementation of hospital management tools.

PMID- 7740146
TI  - [Analysis of costs in hemodynamics and interventional cardiology: how much we
      spend, for what and why].

PMID- 7740148
TI  - [Effects of reoxygenation-induced osmotic edema on cell viability. Study using
      isolated myocytes].
AB  - OBJECTIVE: To investigate the hypothesis that reperfusion edema may kill
      myocytes. METHODS: Adult Sprague-Dawley rat hearts were perfused with a calcium
      free dissociation buffer containing collagenase 0.03% in a Langedorff system.
      Intact cells were selected and myocytes were cultured in adherent pretreated
      dishes. After 3 hours, 80% of cells were rod-shaped. Anoxia was simulated by
      means of metabolic inhibition by adding NaCN 2 mM to the control media, and
      reoxygenation by substituting this media with one of the following media non
      containing NaCN: 1) normo-osmotic (312 mOsm); 2) hypoosmotic (80 mOsm); 3) normo
      osmotic with low Na+ (312 mOsm). A group of cells was kept with control media
      without metabolic inhibition and then submitted to simulated reoxygenation with
      hypoosmotic media (control group). The number of rod, square and round-shaped
      cells was monitored, and cell viability was assessed after 5 min of reoxygenation
      by the Trypan blue test. RESULTS: After 60 min of metabolic inhibition there were
      no differences in the % of cells without hypercontracture among groups
      reoxygenated with normo-osmotic, hypoosmotic, low Na+ normo-osmotic and control
      media (84 +/- 16, 74 +/- 10, 76 +/- 14 and 90 +/- 6% respectively (p = NS). After
      5 min of reoxygenation, these values decreased (p < 0.001) to 19 +/- 6, 11 +/- 9
      and 13 +/- 3% (p = NS), respectively, in groups with normo-osmotic, hypoosmotic,
      and low Na+ normo-osmotic reoxygenation, but were not modified in the control
      group (78 +/- 4). The % of viable cells (Trypan negative) preserved after 5 min
      of reoxygenation was 67 +/- 29% in the group with normo-osmotic reoxygenation, 31
      +/- 23% in the group with hypoosmotic reoxygenation, and 85 +/- 12% in the group
      with low Na+ normo-osmotic reoxygenation (p < 0.001). Exposing cells without
      metabolic inhibition to hypoosmotic media resulted in no significative reduction
      of cell viability. CONCLUSION: Hypoosmotic reoxygenation following prolonged
      metabolic inhibition may kill viable myocytes. This effect is not due to the low
      Na+ concentration in the hypoosmotic medium.

PMID- 7740147
TI  - [Adenosine triphosphate (ATP) in the management of paroxysmal supraventricular
      tachycardia: experience in the neonatal period].
AB  - INTRODUCTION AND OBJECTIVE: The management of supraventricular tachycardia (SVT)
      in infants is somewhat controversial since numerous methods of treatment are
      effective. Regardless of the treatment chosen, it is important to quickly stop
      the tachycardia in neonates with SVT because they may suddenly become
      hemodynamically unstable. METHODS: Seventeen episodes of SVT treated with
      intravenous ATP are studied in 3 newborns (two were preterm infants: 30 and 34
      weeks of pregnancy). Ages at presentation ranged from 2 to 27 days. RESULTS: ATP
      is effective in all episodes of SVT, with a mean intravenous doses between 0.10
      and 0.50 mg/kg/dose. All patients showed short sinus arrest after ATP. No adverse
      side effects or hemodynamics changes occurred after ATP administration.
      CONCLUSIONS: ATP is a safe and reliable antiarrhythmic in neonatal period,
      including prematurity. We reviewed the experience in ATP management of SVT,
      mainly in pediatric population.

PMID- 7740149
TI  - [Amiodarone in the nineties: to whom and what dosage?].

PMID- 7740150
TI  - [Biatrial thrombosis].
AB  - A fifty-eight year old patient presented subacute right heart failure.
      Transthoracic and transesophageal echocardiography revealed thrombi in both
      atria, and initial anticoagulation and subsequent surgical treatment were
      successful. Echocardiography is defined as being decisive to diagnosis, and the
      role of surgery in the treatment of these patients is commented.

PMID- 7740151
TI  - [Sudden death in a 4-month-old infant associated with anomalous origin of the
      left coronary artery].
AB  - We describe the autopsy findings of a 4 months-old boy, who died suddenly after
      an episode of high airway infection of 3 days time. Autopsy examination showed
      cardiomegaly (80 g) with widening of the left cavities and thick and white
      endocardial surface, besides a severe thinning of the cardiac apex at the level
      of the left ventricle. Left coronary origin was in the pulmonary artery trunk.
      Histologically, the myocardium shows endomyocardial fibroelastosis and also
      multiple and extensive areas of old and recent infarcts in the left ventricle.
      The collateral coronary arteries, were increased in number, and branches showed a
      marked intimal oedema and a reduction of the luminal diameter.

PMID- 7740152
TI  - [Defibrillators implanted by cardiologists in the electrophysiological
      laboratory].

PMID- 7740153
TI  - The mother of the pill.

PMID- 7740154
TI  - Activins and the receptor serine kinase superfamily.

PMID- 7740155
TI  - The MAP kinase cascade.

PMID- 7740156
TI  - Expression and signal transduction pathways of gonadotropin-releasing hormone
      receptors.

PMID- 7740157
TI  - The NMDA receptor channel: molecular design of a coincidence detector.

PMID- 7740158
TI  - G protein GTPase-activating proteins: regulation of speed, amplitude, and
      signaling selectivity.

PMID- 7740159
TI  - Ovarian cell differentiation: a cascade of multiple hormones, cellular signals,
      and regulated genes.
AB  - During the development of preovulatory follicles, tonic levels of FSH (and
      steroid) induce expression of aromatase, the LH receptor, and RII beta in a
      coordinate manner. Despite the similar temporal increase in steady-state levels
      of mRNA encoding these proteins, the cis-acting DNA elements and trans-acting
      factors regulating each gene are distinct (Richards, 1993). Whereas the aromatase
      gene has a TATA motif and a single transcriptional initiation site (Fitzpatrick
      and Richards, 1993), both the LH receptor (Wang et al., 1992; Tsai-Morris et al.,
      1993) and RII beta (Kurten et al., 1992; Luo et al., 1992) genes have promoters
      that are GC rich, lack TATA motifs, and initiate transcription at multiple sites.
      The aromatase promoter appears to be regulated, in part, by SF-1, a CRE-like
      region, and possibly another or overlapping region binding an Ad3BP-like factor.
      The RII beta promoter has a region that binds several nuclear proteins, whose
      identity is not yet known. Likewise, the LH receptor promoter elements have yet
      to be clearly defined (Figures 2, 4, and 25; Kurten et al., 1992). FSH can also
      induce the expression of at least three immediate-early genes that encode novel
      kinases or kinase-like proteins (Figure 25). One of these is called serum
      inducible kinase (snk) (Simmons et al., 1992), another is serum and
      glucocorticoid regulated kinase (sgk) (Webster et al., 1993), and a third is
      called pole kinase (Clay et al., 1993). Steady-state levels of snk and sgk mRNA
      are induced rapidly (within a few hours) by FSH in granulosa cells prior to the
      appearance of transcripts for aromatase, LH receptor, and RII beta (T. Alliston
      and J. S. Richards, in preparation). The functional role of these kinases in the
      initial response of granulosa cells to tonic (not surge) levels of FSH remains to
      be elucidated. The cellular signaling pathways mediating the effects of the LH
      surge appear equally or more complex (Fig. 25). Based on data presented herein,
      as well as on analyses of the cloned and expressed LH receptor (Guderman et al.,
      1992), it is clear that low concentrations of LH stimulate adenylyl cyclase, cAMP
      production, and activation of protein kinase A. Higher (surge) concentrations of
      LH also increase IP3 and activation of protein kinase C. GnRH has been used in
      several studies to examine the ability of the protein kinase C pathway to mimic
      effects of high LH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740160
TI  - Oxytocin and oxytocin receptor gene expression in the uterus.

PMID- 7740161
TI  - Molecular genetic analysis of mammalian spermatid differentiation.

PMID- 7740162
TI  - Role of the renin-angiotensin system in blood pressure regulation and in human
      hypertension: new insights from molecular genetics.

PMID- 7740163
TI  - Amphibian metamorphosis: a complex program of gene expression changes controlled
      by the thyroid hormone.

PMID- 7740164
TI  - The molecular and genetic dissection of the retinoid signaling pathway.

PMID- 7740165
TI  - An alternative ligand-independent pathway for activation of steroid receptors.

PMID- 7740166
TI  - The endocrine role in mammalian sexual differentiation.

PMID- 7740167
TI  - Growth hormone-releasing hormone: synthesis and signaling.
AB  - The molecular characterization of GHRH and the GHRH receptor provides a framework
      for understanding the hypothalamic regulation of pituitary somatotroph function.
      The signaling events discerned from our investigation of GHRH receptor structure
      and function form the basis of a model for GHRH action, which is shown in Fig.
      20. GHRH interaction with its seven transmembrane domain Gs-coupled receptor on
      the somatotroph (step 1) leads to the release of growth hormone from secretory
      granules (step 2), which is likely to involve a G protein-mediated interaction
      with ion channels, and to a stimulation of intracellular cAMP accumulation (step
      3) (Mayo, 1992; Lin et al., 1992; Gaylinn et al., 1993). In several cell types
      tested, elevated cAMP leads to the phosphorylation and activation of the
      transcription factor CREB by protein kinase A (Gonzalez and Montminy, 1989; Sheng
      et al., 1991), and one target gene for CREB action is the pituitary-specific
      transcription factor Pit-1 or GHF-1 (step 4) (Bodner et al., 1988; Ingraham et
      al., 1988; McCormick et al., 1990). Pit-1 is a prototypic POU domain protein that
      is required for the appropriate regulation of the growth hormone gene in
      somatotroph cells, thus providing a pathway by which a GHRH signal can lead to
      increased growth hormone synthesis in the pituitary (step 5). In addition, Pit-1
      is likely to directly regulate the synthesis of the GHRH receptor (step 6), in
      that the receptor is not expressed in the pituitary of dw/dw mice that lack
      functional Pit-1 (Lin et al., 1992), and a cotransfected Pit-1 expression
      construct can activate the GHRH receptor promoter in transiently transfected CV1
      cells (Lin et al., 1993). It remains to be determined whether additional direct
      regulation of the GHRH receptor gene in response to the cAMP signaling pathway
      occurs (step 7). The inhibitory peptide somatostatin presumably interacts with
      this same signaling pathway through G protein-mediated suppression of the cAMP
      pathway (Tallent and Reisine, 1992; Bell and Reisine, 1993). In agreement with
      the importance of this signaling system for normal growth, a transgene encoding a
      nonphosphorylatable mutant CREB protein, which blocks the function of the
      endogenous CREB protein, is able to cause somatotroph hypoplasia and dwarfism in
      mice when its expression is targeted to pituitary somatotrophs (Struthers et al.,
      1991). Several steps in the signaling pathway leading to growth hormone secretion
      are subject to disruption, resulting in growth hormone deficiency.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7740168
TI  - Interleukins-1 alpha and -1 beta regulate interleukin-6 expression in Leydig and
      Sertoli cells.

PMID- 7740169
TI  - Calcitonin gene expression in the rat uterus during pregnancy.

PMID- 7740170
TI  - Zone-specific clusterin mRNA expression in the rat epididymis.

PMID- 7740171
TI  - Interleukin-1 alpha inhibition of luteinized human granulosa cell progesterone
      production through influences on associated white blood cells.

PMID- 7740172
TI  - Expression of the Xenopus laevis mineralocorticoid receptor during metamorphosis.

PMID- 7740173
TI  - Pituitary and hypothalamic regulation of sex differences in serum-luteinizing
      hormone levels in gonadectomized rats: in vitro perifusion studies.

PMID- 7740174
TI  - Derivation of novel embryonic stem cell lines and targeting of cyclic AMP
      dependent protein kinase genes.

PMID- 7740176
TI  - Leukemic cell apoptosis caused by constitutively active mutant glucocorticoid
      receptor fragments.

PMID- 7740175
TI  - Retinoid X receptor beta and peroxisome proliferator-activated receptor activate
      an estrogen response element.

PMID- 7740177
TI  - Expression of the short and long forms of the prolactin receptor in murine
      lymphoid tissues.

PMID- 7740178
TI  - 8-Br-cAMP does not convert antagonists of the glucocorticoid receptor into
      agonists.

PMID- 7740179
TI  - Growth hormone and Pit-1 mRNA detection using reverse transcription-polymerase
      chain reaction in adult and developing Ames dwarf mice.

PMID- 7740180
TI  - An environmental antiandrogen.

PMID- 7740181
TI  - Phorbol esters inhibit estrogen-induced uterine DNA synthesis and increase
      apoptosis in uterine epithelium.

PMID- 7740182
TI  - Hypothalamus-specific regulation of gonadotropin-releasing hormone gene
      expression.

PMID- 7740183
TI  - Effects of retinoids on expression of the protooncogene c-myb in rat Sertoli
      cells.

PMID- 7740184
TI  - Role of prolactin in developmental differentiation of hypophysiotropic
      tuberoinfundibular dopaminergic neurons.

PMID- 7740185
TI  - Efficacy of gonadotropin-releasing hormone agonists to induce ovulation following
      low-dose human menopausal gonadotropin stimulation.

PMID- 7740186
TI  - Signaling mechanisms during the response of pituitary gonadotropes to GnRH.

PMID- 7740187
TI  - Molecular genetic analysis of cAMP and glucocorticoid signaling in development.

PMID- 7740188
TI  - The reluctance of house staff to perform mouth-to-mouth resuscitation in the
      inpatient setting: what are the considerations?
AB  - OBJECTIVE: Medical house staff are required to perform cardiopulmonary
      resuscitation (CPR) as part of their job responsibilities. Previously it has been
      shown that house staff are reluctant to perform mouth-to-mouth resuscitation
      (MMR) in an out of hospital setting. Therefore, whether reluctance to perform MMR
      extends to the inpatient setting, and, if so, the reasons for this reluctance
      were investigated. DESIGN: All 74 internal medicine house officers of a large
      metropolitan hospital responded to presentations of hypothetical inpatient
      cardiac arrest scenarios to assess their willingness to perform MMR. SETTING: A
      1200 bed university-affiliated teaching hospital in Los Angeles, California.
      SUBJECTS: All categorical internal medicine house officers at this hospital.
      INTERVENTIONS: This study is a survey which concerns whether the house officer
      would perform mouth-to-mouth resuscitation in different hypothetical cardiac
      arrest scenarios. RESULTS: Forty-five percent would perform MMR on an unknown
      patient and 39% would perform MMR in the elderly patient scenario. Only 16% would
      do MMR on a patient with a small amount of blood on his lips and only 7% would
      perform MMR on a patient with presumed acquired immunodeficiency syndrome.
      Medical housestaff were much more reluctant to perform MMR on elderly, trauma, or
      presumed immunodeficient patients in an inpatient setting than in an outpatient
      setting. All house staff that indicated their unwillingness to perform MMR cited
      fear of human immunodeficiency virus infection as their reason. CONCLUSION:
      Medical housestaff are quite reluctant to perform MMR in an inpatient setting.
      Thus, educating the medical house staff about the percent of patients that
      survive inpatient cardiac arrest and the actual risks of contracting infectious
      diseases, especially HIV infections, from MMR and preventative measures, such as
      effective barrier masks, should result in an increased willingness of physicians
      to perform MMR or mouth-to-mask ventilation on inpatients.

PMID- 7740189
TI  - Quality of bystander cardiopulmonary resuscitation influences outcome after
      prehospital cardiac arrest.
AB  - To evaluate the influence of quality of bystander cardiopulmonary resuscitation
      (CPR) on outcome in prehospital cardiac arrest we consecutively included patients
      with prehospital cardiac arrest treated by paramedics in a community run
      ambulance system in Oslo, Norway from 1985 to 1989. Good CPR was defined as
      palpable carotid or femoral pulse and intermittent chest expansion with inflation
      attempts. Outcome measure was hospital discharge rate. One hundred and forty-nine
      of 334 patients (45%) received bystander CPR. The discharge rate after good BCPR
      (23%) was higher than after no good BCPR (1%, P < 0.0005) or after no BCPR (6%, P
      < 0.0005). There was no difference between no good and no BCPR (P = 0.1114).
      There were no differences in paramedic response interval between the groups, but
      the mean interval from start of unconsciousness to initiation of CPR (arrest-CPR
      interval) was significantly shorter in the group receiving good bystander CPR
      (2.5 min, 95% confidence interval (CI): 1.7-3.3 min) than no good CPR (6.6 min,
      CI: 5.2-8.0 min) or no bystander CPR (7.8 min, CI: 7.2-8.4 min). Bystanders
      started CPR more frequently in public than in the patient's home (58 vs. 34%, P <
      0.0005). Good bystander CPR was associated with a shorter arrest-CPR interval and
      improved hospital discharge rate as compared to no good BCPR or no BCPR.

PMID- 7740190
TI  - Patterns of systemic oxygen utilization in cardiac ischemic syndromes: oxygen
      utilization in cardiac ischemia.
AB  - Cardiac ischemia can present as distinctive clinical syndromes such as acute
      myocardial infarction, cardiogenic shock, sudden cardiac arrest or chronic
      congestive heart failure. All of the clinical syndromes share common
      pathophysiological events including reduction of cardiac output and systemic
      oxygen delivery (DO2) and activation of neurohumoral stress response. The balance
      between systemic DO2 and oxygen consumption (VO2) is maintained by modification
      of systemic oxygen utilization and demands which are essential for tissue
      viability and survival in cardiac ischemic syndromes. Low blood flow and the
      neurohumoral response may influence cellular metabolism (e.g., acute ischemia
      preconditioning and chronic downregulation of aerobic metabolism) and
      microcirculatory perfusion patterns to decrease systemic oxygen demands and VO2
      in harmony with low cardiac output and systemic DO2. The clinical relevance of
      these metabolic adaptations and their influence on the outcome in cardiac
      ischemic syndromes remains unknown.

PMID- 7740191
TI  - Teaching rapid sequence intubation to pediatric emergency physicians: a pilot
      course.
AB  - We describe and evaluate a pilot course designed to teach rapid sequence
      intubation (RSI) to pediatric emergency physicians. A questionnaire was utilized
      to assess participants' self-assessment of knowledge and skills in defined areas
      related to rapid sequence intubation, before and after the course. Thirteen
      pediatric emergency physicians (nine attendings and four fellows) participated in
      the pilot course. A significant increase in self-assessment of knowledge and
      skills was found after the course for most parameters analyzed. These areas
      included: knowledge of indications and contraindications for RSI, knowledge of
      specific sedating and paralyzing agents, knowledge of complications of RSI and
      their management, and level of comfort performing RSI when indicated (P < 0.05).
      We conclude that a formal course can significantly enhance self-assessment
      concerning ability to perform rapid sequence intubation. Further study is
      required to determine if such a course improves performance of this procedure.

PMID- 7740192
TI  - Human factors and safety in emergency medicine.
AB  - A model based on an input process and outcome conceptualisation is suggested to
      address safety-relevant factors in emergency medicine. As shown in other dynamic
      and demanding environments, human factors play a decisive role in attaining high
      quality service. Attitudes held by health-care providers, organisational shells
      and work-cultural parameters determine communication, conflict resolution and
      workload distribution within and between teams. These factors should be taken
      into account to improve outcomes such as operational integrity, job satisfaction
      and morale.

PMID- 7740193
TI  - Long-term survival after successful out-of-hospital resuscitation.
AB  - Between 1983 and 1989, 962 patients in Rotterdam were resuscitated outside
      hospital, of whom 240 (25%) could be discharged alive. A follow-up study was
      performed to determine prognosis in these patients. Of the 240 survivors of out
      of-hospital resuscitation 80% survived after 1 year and 61% after 5 years. During
      the first year, 9% suffered from myocardial (re)infarction and 13% underwent
      coronary bypass surgery or angioplasty. Within the first 3 years after
      resuscitation 60% of the patients were readmitted to hospital. Permanent or
      temporary neurological deficits were observed in 30 patients (14%). Patients with
      a primary arrhythmia without myocardial infarction had a worse prognosis than
      patients with a cardiac arrest in the context of an infarct. Survival was better
      in patients in whom resuscitation was initiated by physicians or ambulance
      nurses, than in patients resuscitated by lay-people. Multivariate analysis
      revealed that this difference could be explained by a larger proportion of
      patients with a primary arrhythmia in the latter group. Since long-term prognosis
      after out-of-hospital resuscitation is satisfactory, programmes for resuscitation
      courses should be stimulated. Such programmes should aim predominantly at
      relatives of patients with known heart disease, police officers and children.

PMID- 7740194
TI  - The need for wider dissemination of CPR skills: are schools the answer?
AB  - The value of instructing members of the public in CPR is now widely recognised,
      but community training schemes which rely largely on volunteers may fail to reach
      their targets. CPR training for lay people is often a once only activity and it
      has been shown that, without revision, skills deteriorate rapidly. By teaching
      CPR in secondary schools all social classes and ethnic groups could be reached,
      and retention of skills improved by regular revision. Health education has shown
      that it may be beneficial to use older pupils as instruction assistants.

PMID- 7740195
TI  - Comparison of adrenergic agonists for the treatment of ventricular fibrillation
      and pulseless electrical activity.
AB  - The primary role of epinephrine for the treatment of ventricular fibrillation
      (VF) and pulseless electrical activity (PEA) is to increase blood flow to the
      myocardium and central nervous system and ultimately improve survival. However,
      despite the administration of epinephrine, survival following VF or PEA is low.
      In an attempt to improve outcome from VF and PEA, alternative adrenergic agonists
      (methoxamine, phenylephrine, norepinephrine) which have different pharmacological
      properties than epinephrine have been evaluated. In order to determine the role
      of alternative adrenergic agonists for the treatment of VF and PEA this paper
      will compare the pharmacological properties and pharmacodynamic effects of these
      drugs to epinephrine. Specifically, receptor physiology along with the effects of
      adrenergic agonists on coronary perfusion pressure, survival, myocardial oxygen
      demand, and cerebral blood flow will be discussed.

PMID- 7740196
TI  - ATP-MgCl2 added to resuscitation improves survival in an experimental model of
      hemorrhagic shock.
AB  - The administration of ATP-MgCl2 may be of benefit in the treatment of shock by
      improving cellular metabolic function during resuscitation. Prior studies have
      reported data from hemorrhage models in which heparinized shed blood is returned
      both during shock and in resuscitation. The purpose of this study was to test the
      effects of ATP-MgCl2 therapy upon blood pressure and survival in an animal model
      of hemorrhagic shock utilizing crystalloid (Lactated Ringer's) resuscitation.
      Adult male Sprague-Dawley rats (340-360 g) were bled 27 cc/kg and maintained in
      shock for 45 min. At the end of the shock period, animals were resuscitated with
      crystalloid at twice the original hemorrhage volume. A blinded three-arm study
      was conducted and animals were assigned to receive either Lactated Ringer's (LR)
      with placebo, LR with MgCl2, or LR with ATP-MgCl2. Blood pressure was monitored
      throughout the procedure and survival time was noted. Post-resuscitation MAP was
      increased in animals treated with ATP-MgCl2. ATP-MgCl2 added to resuscitation
      significantly improved 72-h survival over that of control (LR) animals, and
      animals treated with MgCl2 alone.

PMID- 7740197
TI  - A comparison of two different European EMS centers (Brugge and Gottingen) using
      the same electronic 'cardiopulmonary-cerebral-resuscitation' registration
      program: a preliminary report.
AB  - A preliminary comparison of out-of-hospital cardiac arrest (CA) data registered
      with a common software program (Utstein style) in two different European EMS
      centers is presented. Rather than attempting independently several small-scale
      trials, we prefer to develop in a committed effort a coordinated program of
      active and passive surveillance. Hopefully, this will allow us to determine the
      true European profile and outcome of our out-of-hospital CA victims.

PMID- 7740198
TI  - Ventilatory response to CO2 and hypoxia during cold exposure in awake rats.
AB  - Recently, we have described the effects of hypoxia and of hypercapnia on the
      metabolic (VO2) and ventilatory responses to cold in unanesthetized intact and
      carotid body-denervated (CBD) rats (Gautier et al., J. Appl. Physiol. 73: 847
      854, 1992 and 75: 2570-2579, 1993). In the present paper, we have reanalyzed the
      above results for a more detailed study of the interactions of hypoxia (FIO2 =
      0.12), hypercapnia (FICO2 = 0.04) and changes in VO2 with the ventilatory
      control. The results show that: (1) Compared to normoxia, in hypoxia increments
      in V and VT are proportional to VO2 whereas in hypercapnia increments in
      ventilation (V) and tidal volume (VT) are independent of VO2. In both hypoxia and
      hypercapnia, increases in respiratory frequency (fR) are independent of VO2; and
      (2) Interactions of hypoxia, hypercapnia and VO2 with control of V persist in CBD
      rats but, for a given VO2, V, VT and fR are lower than in intact rats. These
      interactions are essentially similar to those observed during muscular exercise
      performed in normoxia, hypoxia or hypercapnia. It is suggested that during cold
      exposure or muscular exercise, resulting both in increased VO2, there are common
      integrative structures probably located in the hypothalamus which are involved in
      the control of breathing.

PMID- 7740199
TI  - Comparative effects of aging on pharyngeal and diaphragm muscles.
AB  - We hypothesized that aging is associated with alterations in pharyngeal muscle
      structural and contractile properties. Sternohyoid and geniohyoid muscles from
      young (3-4 months) and old (20-21 months) Fischer 344 rats were compared with
      diaphragm muscle. The pharyngeal muscles had significantly lower proportions of
      slow oxidative (SO) fibers compared to the diaphragm, and the percentage of fast
      glycolytic (FG) fibers was significantly higher in the sternohyoid than in both
      the geniohyoid and the diaphragm. With senescence, there was a small but
      significant increase in the proportion of FG fibers and a corresponding reduction
      in the proportion of fast oxidative glycolytic (FOG) fibers in all three muscles.
      The sternohyoid muscle had significantly faster isometric contractile kinetics
      and lower fatigue indexes than the diaphragm. Aging was associated with
      significant worsening of sternohyoid endurance, but no significant alterations in
      sternohyoid twitch kinetics or diaphragm properties. These results indicate that
      in rats the pharyngeal dilator muscles have larger proportions of fast fibers,
      fast contractile kinetics and worse endurance than the diaphragm. Furthermore,
      aging was associated with a shift to a higher proportion of FG fibers with a
      concomitant reduction in proportion of FOG fibers, as well as a decline in
      pharyngeal muscle endurance.

PMID- 7740200
TI  - Time course of histamine-induced bronchoconstriction and its adrenergic and H2
      modulation.
AB  - We characterized the complete time course of histamine-induced
      bronchoconstriction and its modulation via the release of endogenous
      catecholamines and by its actions on H2-receptors in anesthetized,
      tracheostomized, paralyzed, and artificially ventilated mongrel dogs. Respiratory
      resistance (R) and elastance (E) were estimated continuously with a recursive
      least squares estimator. Three protocols were followed in which multiple
      histamine bolus injections were given 1 h apart. We found that the time courses
      of E and R had consistent patterns (transient peak that returned to baseline
      within 1000 sec) even in cases of low mean arterial pressure (MAP). Indomethacin
      pre-treatments prevented tachyphylaxis to repeated i.v. challenges. beta-blockade
      produced a mild increase in baseline and a potentiation of the histamine-induced
      response in E and these effects were not altered with further alpha-or H2
      blockade. Blockade of alpha-receptors increased the time to recovery in both E
      and MAP presumably by decreasing blood flow. Finally, we suggest that preventing
      the H2-receptor induced increase in bronchial blood flow may have increased the
      time to maximal E without affecting the recovery time.

PMID- 7740201
TI  - Isoproterenol augments ATP-evoked Cl- secretion across canine tracheal
      epithelium.
AB  - Using an Ussing chamber, both the posterior epithelial membrane and cultured
      epithelial cell monolayers from canine trachea were used for measurements of
      potential difference (PD) and short circuit current (SCC). Conductance (G) was
      calculated as the ratio SCC/PD. Adenosine (10(-5) to 10(-3) M) failed to produce
      any significant increases in PD and SCC. ATP (10(-6) to 10(-4) M) produced a
      significant transient increase in SCC in a dose-dependent fashion, reaching a
      peak value within 3 min after stimulation. Isoproterenol (ISOP) at 10(-8) M
      itself did not significantly alter the SCC value. In both the epithelial membrane
      and cultured epithelial cells treated with amiloride, however, pretreatment with
      10(-8) M ISOP significantly augmented the ATP-induced SCC rise, whereas G did not
      significantly change. These findings indicate that beta-adrenergic stimulation
      augments Cl- secretion induced by P2-receptor stimulation in airway epithelial
      cells.

PMID- 7740202
TI  - On the use of the alveolar capsule technique to study bronchoconstriction.
AB  - Using the alveolar capsule technique, we studied the time courses of respiratory
      mechanical parameters at various sites on the lung surface during
      bronchoconstriction. Six mongrel dogs were anesthetized, tracheostomized,
      paralyzed and artificially ventilated (12-25 ml/kg, 19-22 breaths/min).
      Sternotomy was performed and alveolar capsules were glued to various parts of the
      lungs. Tracheal pressure and flow and alveolar pressure were measured
      continuously for 25 min after i.v. bolus injections of histamine (0, 0.05, 0.5,
      5.0, 50.0 mg). The challenges were spaced 1 h apart. Estimates of lung tissue
      resistance and elastance were obtained with our recursive least-squares estimator
      (Lauzon and Bates, J. Appl. Physiol., 1159-1165, 1991). We found that the time
      courses of the parameters of most capsules were initially uniform but quickly
      diverged as bronchoconstriction developed. Also, we found that the differences in
      time course of mechanics between alveolar regions either developed randomly with
      step-like features presumably reflecting intermittent opening and closing of the
      airways leading to the various alveolar capsules, or in a progressive dose
      dependent manner, possibly reflecting a gradual but structurally pre-set pattern
      of bronchoconstriction, or with a combination of these two patterns. We explain
      our results in terms of inhomogeneous mechanical properties of the lungs and
      examine some artifacts introduced by the alveolar pressure measurement technique.

PMID- 7740203
TI  - Determination of DLCO and cardiac output from expired gas slopes with cardiogenic
      oscillations.
AB  - Effects of 'cardiogenic oscillations' on alveolar plateau gas concentration slope
      measurements, constant expiratory pulmonary capillary blood flow, and DLCO
      determination have not been previously described. We examined cardiogenic
      oscillations during constant expiratory maneuvers to assess factors influencing
      magnitude of oscillations as well as effect of oscillatory phase at the start and
      end of exhalation measurement period on alveolar gas slope. Five normal
      volunteers performed repeated single breath constant exhalation vital capacity
      maneuvers using test gas containing 2 physiologically 'inert' gases: Helium (He
      Mw 4) and argon (Ar Mw 40). The mixture contained 3 absorbable gases, acetylene
      (C2H2 Mw 26), carbon monoxide (C18O Mw 30), and oxygen. Alveolar plateau slope,
      magnitude of cardiogenic oscillations, relative signal to noise ratios, and
      effect of cardiogenic oscillation phase on measured slope were determined for
      each gas. Cardiogenic oscillations were present for all inert gases. Oscillations
      were less evident for CO. However, the effects on calculated Qc and DLCO were
      negligible. Cardiac oscillations of considerable magnitude are seen during single
      breath constant exhalation maneuvers and affect constant expiratory gas slope
      calculations. Cardiogenic oscillation phase does not have a significant effect on
      measured Qc and DLCO using constant expiratory techniques.

PMID- 7740204
TI  - Oxygen transport by rabbit embryonic blood: high cooperativity of hemoglobin
      oxygen binding.
AB  - Oxygen equilibrium curves (OECs) have been determined in blood of embryonic and
      adult rabbits (Oryctolagus cuniculus) using a thin film method (modified
      Hemoscan). The gestational age of the rabbits was from 12 days to 14 days, the
      end of the embryonic period. Measurements were made at 37 degrees C and a PCO2 of
      21, 42, or 71 mmHg. The most striking finding was an embryonic OEC which was
      steep above 50% saturation. The Hill plot in this upper region gave a mean nH
      value of 5.3 in the embryos, the first finding of nH significantly greater than 4
      in any normal eutherian mammal. On hemolysis, nH dropped below 4. Oxygen affinity
      of 14 day embryonic blood was higher than that of adult blood: respective P50
      values at PCO2 = 42 mmHg were 29.6 mmHg and 32.5 mmHg. The P50s were somewhat
      lower at earlier stages. The Bohr effect was measured (as delta log P50/delta log
      PCO2) in 14 day embryos. Its value was 0.26, about 10% lower than in adults. The
      results show an apparent aggregation of Hb tetramers, as found in marsupials, but
      no right shifting of the embryonic OEC compared to the adult OEC.

PMID- 7740205
TI  - Rheological determinants of mucociliary transport in the nose of the rat.
AB  - The present work was designed to investigate whether the rheological determinants
      for nasal mucociliary transport are the same in the intact preparation (in situ),
      as they are when the mucus is added exogenously to the isolated, mucus-depleted
      frog palate (in vitro). We evaluated the association between estimators of
      mucociliary transport in both conditions and rheological parameters using
      multiple regression techniques. Two kinds of rats were used: (a) specific
      pathogen free (SPF) rats, representing the normal condition of respiratory
      epithelium; (b) non-SPF rats (NSPF), which have a chronic inflammatory process in
      the airways. In situ mucociliary clearance (MCC) was determined by measuring the
      displacement of charcoal particles placed in the nasal septum. In vitro
      mucociliary transport (MCT) of rat nasal mucus was measured using the isolated
      frog palate preparation. Mucus rheologic properties were determined by magnetic
      microrheometry, in oscillatory deformations performed at 1, 10 and 100
      radians/sec. No differences were detected between SPF and NSPF rats in terms of
      rheological parameters. A decreased MCC was found in NSPF in comparison with the
      SPF group, but no differences were observed between groups in terms of MCT, as
      could be predicted by rheological data. When all animals were pooled, in situ
      transport was significantly associated with the viscosity/elasticity ratio,
      whereas in vitro transport was dependent on the total mechanical impedance of the
      mucus sample. In conclusion, in situ mucus transport is influenced by other
      rheological parameters than those associated with in vitro transportability.

PMID- 7740207
TI  - Theoretical validation of the respiratory benefits of helium-oxygen mixtures.
AB  - A theoretical analysis of convective gas transport validates the clinically
      demonstrated advantage of using helium-oxygen mixtures in treating patients with
      respiratory problems. Previous studies have attributed that advantage to the
      ability of helium-oxygen to stay laminar at higher velocities than nitrogen
      oxygen. The present work shows that helium-oxygen does not need to be laminar to
      provide higher flow rates and that its benefits persist under turbulent
      conditions. The analysis is applied to steady flow through the lungs and through
      a circular airway obstruction. A simplified model of the lungs gives pressure
      flow relations that show a significant increase in oxygen flow rate when nitrogen
      is substituted by helium. A similar improvement is found for flow through an
      obstruction. For a given pressure difference across the lungs or across an
      obstruction, the turbulent flow rate of oxygen increases by approximately 50%
      when nitrogen is replaced by helium in a mixture containing 20% oxygen.

PMID- 7740206
TI  - Cigarette smoke-induced bronchoconstriction and release of tachykinins in guinea
      pig lungs.
AB  - Two series of experiments were carried out to determine whether the release of
      tachykinins is involved in the bronchoconstriction induced by inhalation of
      cigarette smoke in guinea pigs. In the first series, cigarette smoke consistently
      induced bronchoconstriction (delta RL = +203% and delta Cdyn = -46%) in
      anesthetized guinea pigs, and the response was only partially blocked by
      bilateral cervical vagotomy. However, the smoke-induced bronchial constriction
      was completely abolished in animals receiving a systemic capsaicin pretreatment
      to destroy the tachykinin-containing C-fiber afferents. In the second series, the
      bronchoconstrictive effect of cigarette smoke was increased by approx. three
      times in isolated perfused guinea pig lungs when phosphoramidon (3 x 10(-6) M)
      was added to the perfusate to prevent the degradation of tachykinins after their
      release. Moreover, the enhanced bronchomotor response to smoke was accompanied by
      an overflow of neurokinin A-like immunoreactivity (LI) and calcitonin gene
      related peptide -LI in the pulmonary effluent. These studies showed that
      cigarette smoke triggers the release of tachykinins in the lungs, which plays an
      important role in the smoke-induced bronchoconstrictive effect in guinea pigs.

PMID- 7740208
TI  - Scaling of transepithelial potential difference in the mammalian trachea.
AB  - Tracheal epithelia of different mammalian species differ widely with regard to
      the relative rates of Na+ absorption and Cl- secretion. However, the short
      circuit current, a measure of total ion transport, appears to be consistently
      greater in large than in small mammals. Thus, we hypothesized that the in vivo
      tracheal electrical potential difference (PD) would vary among species as a
      function of body mass (M). To test this hypothesis we measured PD in ten
      mammalian species that ranged 1000-fold in mass. The results in mV (mean +/- SE,
      lumen negative) were: 11.4 +/- 1.0 in mice; 11.6 +/- 1.2 in gerbils; 12.9 +/- 1.4
      in rats; 19.3 +/- 0.9 in guinea pigs; 27.2 +/- 2.2 in ferrets; 23.0 +/- 1.6 in
      cats; 27.0 +/- 0.6 in rabbits; 32.5 +/- 2.6 in dogs; 37.0 +/- 1.9 in sheep; and
      49.0 +/- 3.3 in pigs. Log-log correlation analysis of mean PD (in mV) and M (in
      kg) yielded PD = 20.9 M0.19 (r = 0.96, P < 0.001). Analysis of published short
      circuit current (SCC, in microA/cm2) data revealed a similar relationship: SCC =
      38.2 M0.21. Thus, the transepithelial electrical potential and active charge
      transport by the tracheal epithelium are allometric variables that may have
      direct physiological significance. These results raise questions regarding the
      importance of net osmotic solute and water transport across the tracheal
      epithelium.

PMID- 7740209
TI  - Influence of vagal afferents on diphasic ventilatory response to hypoxia in
      newborn lambs.
AB  - The effect of vagal afferents on the ventilatory response to hypoxia was studied
      in eleven awake newborn lambs. Tests were repeated before and after vagotomy in
      the same lambs in two conditions: with intact upper airways and after intubation.
      During hypoxia, a diphasic pattern of ventilatory response was observed in both
      vagotomized and intact lambs. However, face mask-breathing vagotomized lambs had
      a blunted increase in ventilation (VI) to hypoxia as compared with intact lambs
      (P = 0.0001) and they showed an expiratory braking during all hypoxic time.
      Furthermore, the normal increase in frequency (f) to hypoxia was abolished after
      vagotomy. After intubation, expiratory braking disappeared and, consequently,
      magnitude of the VI response to hypoxia was similar in intact and vagotomized
      lambs. These changes were due to improved tidal volume response in vagotomized
      intubated lambs (P < 0.002) with no significant change in f response. We
      concluded that, in awake newborn lambs, vagal afferents are essential for
      maintaining the pattern and the magnitude of the ventilatory response to hypoxia,
      the latter by controlling the motor output to the larynx.

PMID- 7740210
TI  - Regulation of human airway surface liquid.
AB  - Human airways are lined with a film of liquid from 5-100 microns in depth,
      consisting of a periciliary sol around and a mucous gel above the cilia.
      Microscopical studies have shown the sol to be invariably the same depth as the
      length of the cilia, and we discuss possible reasons for this. The composition
      and sources of the airway surface liquid are also described. In addition the
      forces regulating its volume are analyzed. Several airway diseases are
      characterised by dramatic changes in the volume and composition of airway liquid.
      We review recent research suggesting that the accumulation of airway mucous
      secretions in cystic fibrosis is caused by alterations in active transport of
      ions and water across both the surface and gland epithelia.

PMID- 7740211
TI  - Vascular distension in muscles contributes to respiratory control in sheep.
AB  - It has recently been proposed that afferent fibers from skeletal muscle could
      sense the state of the microvascular circulation, linking ventilation to the
      degree of peripheral perfusion or vascular distension (Huszczuk et al., Respir.
      Physiol., 91:207-226, 1993). Ventilatory and circulatory responses to
      manipulation of peripheral vascular pressures in the hind limbs of anaesthetized
      (sodium thiopental) sheep were examined. Inflatable balloons were placed at the
      caudal ends of the abdominal aorta and the vena cava (Vc). Aortic (Ao) occlusion
      induced a consistent normocapnic decrease in minute ventilation (VE). In
      contrast, VE increased significantly during vena cava obstruction, leading to
      hypocapnia. Small changes in systemic blood pressure were observed (+7 mmHg for
      Ao occlusion and -12 mmHg during Vc obstruction). Moreover, inflation of the
      caval balloon superimposed on a previously established Ao occlusion, preventing
      venous drainage of anastomotic inflow, resulted in a significant rise in distal
      vascular pressures with trivial changes in systolic blood pressure. This led to a
      gradual rise of VE, despite further reduction of the CO2 flux to the lungs. The
      subsequent deflation of the aortic balloon, exposing the hindlimb vasculature to
      aortic pressure, resulted in an even more profound hypocapnic hyperpnea. The
      concurrent arterial blood pressure changes were too small to possibly involve the
      ventilatory component of the arterial baroreflex. We therefore hypothesize, that
      perfusion-related afferent signals within the muscles could contribute to
      respiratory homeostasis by maintaining ventilation of the lungs commensurate with
      the circulatory state of the muscular apparatus.

PMID- 7740212
TI  - Properties of rapidly adapting receptors of the airways in monkeys (Macaca
      mulatta).
AB  - The properties of rapidly adapting receptors (RARs) of the airways were examined
      in anaesthetised, artificially ventilated, paralysed and thoracotomised monkeys.
      The RARs were identified (i) by their rapid adaptation to a maintained inflation
      and forced deflation of the lungs and (ii) by their conduction velocity
      measurements. Right atrial (n = 17) and left atrial (n = 13) injections of
      histamine (10 micrograms/kg) stimulated the RARs. The stimulation was associated
      with an increase in peak intratracheal pressure. Right atrial injections of
      phenyl diguanide (n = 6, 10 micrograms/kg) and 5-hydroxytryptamine (n = 6, 10
      micrograms/kg) did not produce a significant stimulation of the RARs.
      Administration of irritant vapours such as ammonia, (n = 12), cigarette smoke (n
      = 8), alcohol (n = 10), acetone (n = 10) and ether (n = 7), caused a significant
      stimulation of the RARs. This stimulation occurred in spite of a significant
      decrease or no change in peak intratracheal pressure. During mild degrees of
      pulmonary venous congestion produced by graded increments in mean left atrial
      pressure (+5 and +10 mmHg), there was a graded increase in RAR (n = 6) activity.
      The present study shows the existence of the RARs in the airways of the rhesus
      monkey. These receptors are stimulated (i) by administration of agents which
      cause bronchoconstriction (ii) by vapours which cause airway irritation and (iii)
      in conditions which cause an expansion of the extravascular space in airways.

PMID- 7740213
TI  - Possible role of dopamine in ventilatory acclimatization to high altitude.
AB  - Ventilatory acclimatization to high altitude is accompanied by increased hypoxic
      (HVR) and hypercapnic (HCVR) ventilatory responses which may reflect increased
      carotid body chemosensitivity. Dopamine is an inhibitory neuromodulator of the
      carotid body and its activity may be reduced by hypoxic exposure. To determine
      whether decreased dopaminergic activity could account for the increased
      chemosensitivity of acclimatization, we examined the response to peripheral
      dopamine receptor (D2) blockade with domperidone on HVR and HCVR in awake cats
      before and after exposure to simulated altitude of 14,000 ft for 2 days. During
      anesthesia, we also examined the effects of domperidone on carotid body responses
      to hypoxia and hypercapnia in acclimatized and low altitude cats. Two days'
      exposure to hypobaric hypoxia produced an increase in HVR and HCVR. Before
      acclimatization, domperidone augmented HVR and HCVR, but there was no effect
      after acclimatization. In anesthetized low altitude cats, domperidone increased
      carotid body responses to hypoxia and hypercapnia, but had no effect in
      acclimatized cats. These results indicate that decreased endogenous dopaminergic
      activity may contribute to increased ventilatory and chemoreceptor responsiveness
      to hypoxia and hypercapnia during hypoxic ventilatory acclimatization.

PMID- 7740214
TI  - Respiratory failure due to altered central drive during inspiratory loading in
      rabbits.
AB  - Mechanisms of respiratory muscle dysfunction leading to respiratory failure
      during incremental inspiratory threshold loading were studied in unbound
      spontaneously breathing rabbits during light and deeper anesthesia. Low or high
      frequency contractile fatigue was not found at the point of respiratory failure
      in any of the animals. On the other hand, alterations in central drive to the
      diaphragm played a dominant role in the observed respiratory failure. In animals
      receiving light anesthesia the intensity of central drive increased with loading,
      but then fell as respiratory failure approached. In all animals the intensity of
      central drive at peak activation and at the point of respiratory failure was
      submaximal, in spite of the diaphragm's ability to generate additional forces. In
      addition, the time tension index of the diaphragm rose in response to increasing
      loads to a level reported to produce contractile fatigue, at which time the index
      peaked and then fell in spite of increasing load demands. The fall in the time
      tension index as respiratory failure approached was due primarily to a fall in
      inspiratory time and duty cycle. Ultimately, there was an abrupt cessation in
      central drive resulting in apnea. These findings suggest that alterations in
      central drive play a major role in respiratory muscle dysfunction and respiratory
      failure associated with inspiratory loading in unbound spontaneously breathing
      rabbits.

PMID- 7740215
TI  - Effect of intramedullary procaine injection on tracheal tone and phrenic
      neurogram.
AB  - To map the superficial locations which are involved in the control of respiration
      and tracheal smooth muscle tone in ventrolateral medulla, we examined the effects
      of local anesthesia on phrenic activity and tracheal tone in twelve anesthetized,
      paralyzed, and artificially ventilated dogs. 0.5 microliter of 5% procaine was
      injected 0.3 to 0.5 mm below the surface unilaterally to the ventral superficial
      layer (from the rostral part of the trapezoid body to the caudal hypoglossal
      rootlets and lateral from the pyramids to 5.5 mm from the midline), which
      included rostral, intermediate and caudal areas, and the area lateral to the
      hypoglossal rootlets. The peak amplitude of the integrated phrenic neurogram was
      decreased by procaine injection to the intermediate area and the area lateral to
      the hypoglossal rootlets. Tracheal tone decreased only by procaine injection to
      the intermediate area. In the intermediate area, some injections decreased either
      phrenic output alone or tracheal tone alone. These results suggest that the two
      ventral medullary areas, i.e. the intermediate and caudolateral parts, contain
      neural structures which are involved in the shaping of phrenic output, but only
      the intermediate area is involved in the regulation of tracheal tone. It is also
      suggested that, in the intermediate area, the structures responsible for the
      maintenance of respiration and tracheal tone are, at least in part, separable.

PMID- 7740216
TI  - Endogenous opioids modulate ventilation in the obese Zucker rat.
AB  - This study evaluated the modulatory role of endogenous opioids on ventilation in
      young and mature, lean and obese male Zucker rats. Naloxone, an opioid receptor
      antagonist, and saline (control) were administered subcutaneously to awake rats,
      and ventilation in air and in response to an hypoxic and an hypercapnic gas
      challenge measured. In response to naloxone young, obese but not lean rats
      exhibited a marked increase of ventilation in all three conditions. Older obese
      Zucker rats that were morbidly obese breathed at a frequency of over 200 breaths
      per minute and showed only a modest increase of ventilation in response to
      naloxone. Older lean rats increased ventilation with naloxone only when exposed
      to hypercapnia. Unlike the stimulatory effects hypoxia and hypercapnia had on
      ventilation in older, lean rats, the ventilatory responses of the obese, older
      rats to hypoxia and to hypercapnia were blunted. We conclude that the obese
      Zucker rat may be a good animal model to assess how chest wall loading and
      endogenous opioids interact in the development of ventilatory control
      abnormalities.

PMID- 7740217
TI  - The experience of cancer and its meaning. Introduction.

PMID- 7740218
TI  - The meaning of cancer pain.
AB  - Pain is a common symptom in cancer and one experienced both by patients and
      family caregivers. A neglected area of pain management is enhancing the
      individual's ability to derive the meaning from pain and suffering associated
      with illness. Because pain is often a metaphor for impending death, the meaning
      derived from pain may contribute to the ultimate meaning of death for the
      individual. This article provides case examples and analysis of the search for
      meaning in cancer pain.

PMID- 7740219
TI  - The meaning of cancer therapy: bone marrow transplantation as an exemplar of
      therapy.
AB  - Cancer touches all dimensions of life and consequently all realms of personal
      meaning including people's beliefs in an orderly and controllable world.
      Regaining a belief in a comprehensible world often begins with the confirmation
      of a definitive diagnosis and the initiation of therapy. The meaning of therapy
      will vary depending on the availability of viable treatment options, the natural
      history of cancer, the daily challenges of living with cancer, and the outcome of
      treatment. This article reviews the literature on the meaning of cancer therapy,
      explanatory models of therapy, and the meaning of personal control during
      treatment. A qualitative study of 23 adults with leukemia who were waiting to
      undergo a bone marrow transplantation (BMT) was conducted to describe the
      personal meaning of leukemia and BMT. The findings indicate that seeking
      confirmation for the diagnosis of leukemia is often impersonal, fraught with
      uncertainty, and surrounded by an unexplained sense of urgency. When making the
      decision to undergo BMT, people transformed the biomedical estimates of survival
      into personal terms to humanize the odds and to inflate their perceived chances
      of survival. Before undergoing BMT, individuals recalled their previous
      experiences with cancer therapy in an effort to make the unknown future more
      predictable. Ways to self-monitor daily progress and suggestions for mitigating
      the devastating effects of bad news were identified. Physicians were identified
      as controlling the BMT treatment regimen, whereas nurses were perceived as
      controlling the daily care routines. Implications include the need to give
      patients preparatory information about what to expect in therapy as well as the
      need to help them identify how they can cope effectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7740220
TI  - Culture and the meanings of cancer.
AB  - This article proposes that the nurse understand culture ideationally in terms of
      models of reality. A distinction is made between cultural and individual models,
      and between lay persons' models of sickness and practitioners' models. These are
      described and discussed in relation to the meanings of cancer. A role for the
      nurse as a cultural broker, negotiating meanings across the patient-practitioner
      divide, is outlined. Material taken from the case studies of two cancer patients
      is used to illustrate how these patients modeled their illness experience and how
      the nurse might use such information to better enlist patient cooperation in the
      management and treatment of their illness.

PMID- 7740221
TI  - Whys and wherefores: adult patient perspectives of the meaning of cancer.
AB  - Theory and empirical evidence suggest that the search for meaning is a
      significant part of the cancer experience. Yet differences exist in how the
      construct "search for meaning" is conceptualized. In this article, the meaning of
      cancer is discussed using four approaches: (1) casual explanations, (2) selective
      incidence, (3) responsibility, and (4) significance. Research describing these
      approaches to the process of searching for meaning among persons with cancer is
      reviewed. Several studies have investigated cancer patients' casual explanations:
      the most frequently cited causes include God's will, heredity, chance, life-style
      and personal factors, and environment. Whereas no studies have focused explicitly
      on the phenomenon of selective incidence (eg, asking "why me?"), a few
      investigations have begun to explore cancer patients' attributions of
      responsibility. These investigations have identified projections of
      responsibility/blame for cancer such as chance, God, others, or the environment.
      Research describing the significance, which is usually positive, that persons
      with cancer ascribe to their illness is also reviewed. Such meanings for cancer
      identified include reprioritization of goals, changed lifestyles and values,
      increased appreciation for nature and others, and spiritual development.
      Responses to the need for meaning vary; indeed, some persons with cancer do not
      perceive that they "search for meaning." The nursing implications of these
      various responses to meaning making are presented.

PMID- 7740222
TI  - What cancer means to me.

PMID- 7740223
TI  - Cancer and the partner relationship: what is its meaning?
AB  - When cancer occurs, it is an illness that has meaning for the lives of all
      members of the family. This article focuses on the meaning and significance of
      the illness for the partner relationship, both the individuals within the
      relationship and the dyad. Results of two studies are presented: one study is
      based on in-depth interviews with 50 individuals who were newly diagnosed with
      cancer and their partners, and the other study used questionnaires from 412
      patients and 175 partners to obtain statistical data. Findings pointed to the
      importance of meaning in the adjustment of individuals, as well as the dyad.
      Interview data indicated that patients and their partners searched for meaning in
      the illness that would decrease its threat, and statistical analyses showed the
      significance of meaning as it applies to specific aspects of adjustment. The
      importance of considering meaning in care that is directed toward the prevention
      of problems within the dyad, which can occur as a result of coping with the
      stress of cancer are emphasized, and some specific recommendations are made.

PMID- 7740224
TI  - The meaning of cancer to children.
AB  - The meaning of cancer to children depends on a variety of individual and family
      characteristics, including the child's developmental and cognitive level,
      previous life experiences, the context of the illness, the family member with
      cancer, and family relationships. Cancer may mean alterations in physical
      characteristics, self-concept, feelings, and life-style, as well as loss of
      support and a need for information. This article reviews the cognitive, personal,
      and social meaning of cancer to children who have cancer, to those whose siblings
      have cancer, and to children of parents with cancer.

PMID- 7740225
TI  - The meaning of cancer and oncology nursing: link to effective care.
AB  - A better understanding of the meaning of cancer and oncology nursing may yield
      insights that will help identify ways in which nurses can obtain the resources
      they need to meet their own needs and to provide effective care. This article
      briefly reviews literature on job stress, burnout, coping, and job satisfaction
      and summarizes our research on nurses' descriptions of the meaning and nature of
      their work with cancer patients. Nurses described having three important roles:
      maintaining the goals and values of health care; participating in the patients'
      experiences; and reconciling the health care values and the patients' experiences
      (ie, the other two roles). Aspects that are rewarding are also difficult and
      individual experiences and perceptions changed the meaning of work, the needs
      nurses have, and the care they provide. The work of nursing may be most
      satisfying when nurses can articulate the meaning of their work and most
      effective when they understand how these meanings affect patient care.

PMID- 7740226
TI  - Clinical commentary: promoting meaning in the lives of cancer survivors.
AB  - In clinical settings, nurses look for ways to encourage and to understand their
      patients' thoughts about the meaning of an illness in their lives. The meaning of
      illness is appreciated when thoughtful communication that respects the
      individual's needs and responses. By encouraging patients to describe their
      thoughts, hopes, and fears about their illness, clinicians will understand what
      is meaningful in life. Because creating meaning is an individual process, nurses
      must listen to the patient's personal story and look for the meaning of illness
      imbedded in it.

PMID- 7740227
TI  - The significance of suffering in cancer care.
AB  - Understanding suffering as a possible meaning of cancer for patients and families
      is a necessary part of cancer nursing care. This article presents a discussion of
      suffering as a possible meaning of cancer for patients and family members.
      Suffering is addressed in the context of its definition as an experience of the
      whole person. First, to illustrate suffering, a narrative of a young man treated
      for leukemia with bone marrow transplantation is presented. The narrative focuses
      on the man's suffering as he struggles to make meaning of what has happened to
      him, a struggle that ends with his death. The second part of the article presents
      eight aphorisms or succinct principles of suffering. Each aphorism is discussed
      with examples from the case narrative and related literature.

PMID- 7740228
TI  - [Datura stramonium poisoning: the diagnosis is clinical, treatment is
      symptomatic].
AB  - Datura stramonium is a hallucinogenic plant found in urban or rural areas. It
      contains three main toxic alkaloids: atropine, scopolamine, and hyosciamine.
      Consumption of any part of the plant can result in severe anticholinergic
      toxicity. Clinical symptoms are those seen in atropine poisoning, particularly
      hallucinations and mydriasis. Prognostic is good in this study. Patients always
      require hospitalisation because of agitated behavior. Symptomatic treatment is
      efficient. Clinicians should be aware of the potential abuse of botanicals such
      as jimson weed to avoid excessive investigations.

PMID- 7740229
TI  - [Osteoarticular tuberculosis. Diagnostic contribution of local sampling].
AB  - Bone and joint tuberculosis have recently gained a renewal of interest,
      especially with the spread of HIV infection which may increase its frequency.
      Bone and joint locations of tuberculosis are pauci-bacillary often requiring
      local sampling in order to confirm the diagnosis and to initiate early therapy.
      From 1983 to 1992 we have studied 19 patients with bone and joint tuberculosis.
      Seventeen local sampling were performed: 12 biopsies and five abscess punctures.
      Pathological examination of samples disclosed diagnosis of tuberculosis in eight
      cases out of 12. Among the remaining four patients, direct smear was positive
      once, and cultures grew Mycobacterium tuberculosis in two, yielding the diagnosis
      in 11 out of the 12 patients. Bacteriological and pathological examinations were
      non contributive in only one patient. Microbiological examination of pus
      disclosed two positive direct smear and three positive cultures. Treatment lasted
      9 to 18 months. The outcome was favourable in all patients.

PMID- 7740230
TI  - [Morphological imaging in the diagnosis of dementia. II. Vascular dementia].
AB  - Magnetic resonance imaging (MRI) and CT-scan are crucial for the diagnosis of
      cerebrovascular diseases. Multi-infarct dementias may be divided into (i)
      dementias due to multiple cortical infarcts and (ii) dementias due to multiple
      lacunar infarcts in the basal ganglia, thalamus and hemispheric white matter,
      usually associated with leukoaraiosis. A single infarct located in the thalamus
      or in the left angular gyrus may also induce dementia. Abnormalities of the
      cerebral white matter, so-called leukoaraiosis, are usually the consequence of a
      cerebrovascular disease and may be called Binswanger's disease in severe cases.
      However, leukoaraiosis is not specific of vascular dementia and may also be found
      in Alzheimer's disease and even in normal aging.

PMID- 7740231
TI  - [Leg ulcers in systemic diseases].
AB  - The collagen vascular diseases and vasculitis, in particular, are occasionally
      associated with chronic, relapsing lower extremity ulcerations. Different
      mechanisms can induce such ulcerations, and an understanding of the type of
      ulcerations is important in the differential diagnosis of patients with leg
      ulcerations in general, and management of these patients in particular. In this
      review, the authors analyze the various mechanisms of the leg ulcerations in
      these patients and their treatments: vasculitis, thrombosis, traumatisms,
      calcinosis, panniculitis, pyoderma gangrenosum, infections, and induced by
      treatments.

PMID- 7740232
TI  - [Thyrotoxic periodic paralysis. Discussion of the role of Na-K-ATPase, apropos of
      a case].
AB  - We report a case of thyrotoxicosis periodic paralysis (TPP), occurring as a
      complication of a Grave's disease in a 31 year-old Caucasian male. It has been
      suggested that the membrane Na-K pump was involved in the pathogenesis of this
      complication. In our patient, before treatment, the activity of erythrocyte Na-K
      ATPase was significantly decreased, as compared with healthy subjects (228nmol
      Pi/mg prot/h versus 298 + 60 nmol Pi/mg prot/h) and went back to normal levels
      post treatment. The activity of this enzyme seems to be prone to genetics factors
      as well as environmental ones. This would explain the higher incidence of TPP in
      male and in asiatic people. However, other reports emphasize the role of Na-K
      pump-independent potassium influx, which would be more specific of TPP.

PMID- 7740233
TI  - [Neuropsychic side-effects of therapeutic doses of zipeprol]].
AB  - We report the two first cases of neuropsychic side-effects with zipeprol (non
      opiate antitussive) given at therapeutic doses. In both cases, the patients
      showed confusion, whereas, hallucinations occurred only in one case. The
      anticholinergic activity of zipeprol might explain these effects. These two cases
      are in agreement with zipeprol central nervous system action.

PMID- 7740234
TI  - [Pseudolymphoma induced by carbamazepine. Apropos of 2 cases].
AB  - We present two pseudolymphoma occurring 8 days and 1 month after carbamazepine
      introduction. Both patients present fever, rash, generalized lymphadenopathy and
      hepatosplenomegaly in the second case. Hematologic abnormalities included anemia,
      eosinophilia, hepatic cytolysis. Histologic evaluation of a lymph node biopsy
      specimen demonstrated near-total effacement of the nodal architecture mimicking a
      lymphoma. Gene rearrangement studies proved the benign nature of the
      proliferation. Carbamazepine-induced lymphoproliferative disorders are relatively
      rare with only 38 observations published. The pathogenesis is uncertain. Immune
      dysregulation is probable. Morphologic and immunophenotypic data must be
      completed by gene rearrangement studies. Corticoid therapy is useless. The
      evolution is favorable after the cessation of carbamazepine.

PMID- 7740235
TI  - [Disseminated intravascular coagulation associated with prostatic cancer].
AB  - Disseminated intravascular coagulation (DIC) associated with prostate
      adenocarcinoma is a bad prognostic sign. Most of the cases are limited to
      biological abnormalities. Some, however, come to medical attention due to
      thromboembolic or hemorrhagic complications. We report 4 such cases and review
      the pertinent literature. The characteristic features are low platelets and
      coagulation factors in an elderly man. In two out of the four cases, bleeding due
      to the DIC revealed the cancer. All patients received hormonotherapy and heparin.
      The worst fate (case 3) was a subacute one with no effect of the drugs and death
      in a short time. The other cases went into a five- to seven months remission
      before uncontrollable bleeding led to death. No favorable effect of the
      chemotherapy was observed. Thus, new treatments are sought for this rare but
      ominous complication of prostate cancer.

PMID- 7740236
TI  - [An uncommon case of sciatica].

PMID- 7740237
TI  - [Capillary hyperpermeability syndrome: a new case].

PMID- 7740238
TI  - [Osteoarticular tuberculosis: contribution of joint puncture and synovial
      puncture-biopsy].

PMID- 7740239
TI  - [Hemorrhagic fever with renal syndrome].

PMID- 7740240
TI  - [Pseudopheochromocytoma in a parkinsonian patient treated with selegiline].

PMID- 7740241
TI  - End-of-life family decision-making from disclosure of HIV through bereavement.
AB  - End-of-life decision-making is conceptualized as the foreground against the
      background of a family, transitional model of illness with the human
      immunodeficiency virus (HIV). Both foreground and background represent new
      knowledge and theory development emerging from six research studies over a 7-year
      period. The research was phenomenological, longitudinal, ethnographic,
      descriptive survey, narrative, and grounded using the constant comparative
      method. In all, 100 families were studied in their home settings in the District
      of Columbia and 29 states across the United States. Throughout the transitional
      process from disclosure of HIV through bereavement, families engaged in end-of
      life decision-making. Their decision-making style was primarily cognitive or
      primarily emotional or somewhere in between. Families using a cognitive style of
      decision-making were less disrupted and more able to surmount hurdles and move
      toward goals. Exemplars from 23 families illustrated family decision-making and
      components of the transitional, family model.

PMID- 7740242
TI  - Contributions to nursing science: synthesis of findings from adaptation model
      research.
AB  - Researchers who had used the Roy Adaptation Model (RAM) to guide their individual
      investigations collaborated to enhance knowledge development about adaptation of
      adults to actual and potential health problems. The purpose of this article is to
      present the synthesis of findings across selected studies that used the RAM. From
      this synthesis, middle-range theories were identified that in turn provided the
      scientific rationale for development and testing of clinical interventions.
      Contributions to the advancement of nursing science include a method to
      strengthen the relationships between research, theory, and practice; and
      increased understanding of the process of adaptation in adults; support for the
      efficacy of the RAM for nursing practice; and the benefit of collaboration
      between nursing researchers using the same model to guide their work.

PMID- 7740243
TI  - The relationship between spiritual perspective, social support, and depression in
      caregiving and noncaregiving wives.
AB  - The purpose of this study was to compare the relationships between spiritual
      perspective, social support, and depression in two groups of adults: caregiving
      wives of dementia victims and noncaregiving wives of healthy adults. Hypotheses
      predicted that increased spiritual perspective would be associated with increased
      social support and decreased depression in caregiving wives. Hypotheses also
      predicted that spiritual perspective would be more strongly associated with these
      variables in caregiving wives. Spiritual perspective was not significantly
      related to social support or depression in the caregivers. The relationships
      between these variables, however, were noted to be stronger in caregiving wives
      than in noncaregivers. Employment and increased availability of support were
      associated with decreased depression in caregivers.

PMID- 7740244
TI  - Benefits and practical use of cross-training in sports.

PMID- 7740245
TI  - Measurement of anaerobic work capacities in humans.
AB  - The development of simple, noninvasive tests of work capacities, underpinned
      primarily by anaerobic metabolism, proliferated in the early 1970s. A 30-second
      maximal cycle test developed at the Wingate Institute initiated efforts to
      develop work tests of anaerobic capacities. Such tests can be developed using any
      ergometer which simulates competitive conditions and enables an accurate
      determination of mechanical work output. A 10-second all-out test is commonly
      used to measure maximal work output generated primarily via the hydrolysis of
      high-energy phosphagens (i.e. the alactic work capacity). In contrast, a variety
      of constant-load and all-out tests of anaerobic (alactic plus lactic) work
      capacity have been proposed. It has been suggested that all-out tests provide
      more information about physiological capabilities and are easier to apply than
      constant-load tests. The optimal duration for an all-out test of anaerobic work
      capacity is proposed at 30 seconds, a duration which may also provide the basis
      for the development of accurate field tests of anaerobic capacity. There is
      evidence that the y-intercept of the maximal work-derivation regression is a
      valid work estimate of anaerobic capacity in athletes, although its utility is
      undermined by the number of tests required for its derivation.

PMID- 7740247
TI  - Exercise programmes in the treatment of children with learning disabilities.
AB  - Learning disability is characterised by a discrepancy between achievement and
      assessed intellectual ability. Children with this problem commonly (but not
      invariably) show impaired motor proficiency, as assessed by such instruments as
      the Bruininks-Oseretsky Test of motor proficiency. It has been hypothesised that
      poor motor performance and/or poor social skills lead to exclusion from games,
      creating a vicious cycle of decreasing participation, decreasing competence, a
      deterioration of self-worth and increasing social maladjustment. Attempts to
      break the vicious cycle with programmes designed to enhance motor proficiency
      have been uniformly unsuccessful. There is limited experimental evidence to
      support the view that structured physical activity programmes with an embedded
      social skills training component can be an effective method of enhancing both
      actual motor ability and self-perception of physical and academic competence.
      However, a controlled comparison with small-group, academic instruction has shown
      that, from the educational perspective, a physical activity-based intervention is
      no more effective than other forms of special attention. The main argument for
      delivering social skills training through a physical activity programme lies not
      in a unique impact upon learning disability, but rather in terms of the other
      well-established long term health benefits of exercise.

PMID- 7740246
TI  - Exercise prescription for individuals with metabolic disorders. Practical
      considerations.
AB  - Regular exercise has been recognised as an important component in the management
      of patients with diabetes mellitus. In addition to acutely lowering blood
      glucose, exercise training improves glucose tolerance and peripheral insulin
      sensitivity, contributes to weight loss and reduces several risk factors for
      cardiovascular disease. When proper precautions are taken to prevent
      hypoglycaemia, individuals with diabetes can enjoy the same benefits from
      exercise as nondiabetic healthy individuals. As a guideline, moderate intensity,
      aerobic endurance activities should be performed for 20 to 40 minutes at least 3
      times a week. Blood glucose should be monitored, and insulin dose and
      carbohydrate intake adjusted based on the blood glucose response to the type and
      duration of exercise. This review will summarise current understanding of the
      therapeutic role of exercise in the treatment of diabetes and will present
      guidelines for prescribing exercise in diabetic patients.

PMID- 7740248
TI  - Skier's thumb. Treatment, prevention and recommendations.
AB  - Skier's thumb is an injury to the ulnar collateral ligament (UCL) of the thumb
      metacarpophalangeal joint (MCPJ) which has a serious risk of disabling chronic
      instability if not treated adequately. The lesion most often occurs in skiers
      when the ski pole forces the thumb to deviate radially. Strapless poles do not
      decrease the incidence of skier's thumb, but if skiers are trained to discard the
      pole during a fall the risk might be reduced. Clinical and anatomical findings
      and the understanding of the injury mechanism show that stability testing
      (performed with the joint in full flexion) and additional standard radiographs
      remain the keystones in decision making in all MCPJ sprains. Protective splinting
      is advocated in stable, undisplaced avulsion fractures and incomplete ligamentous
      lesions of the UCL. However, surgery should not be delayed where there are
      displaced bony avulsion fractures, and where a complete ligamentous rupture is
      suspected because of a more than 30 degrees stressed radial deviation and more
      than 20 degrees difference compared with the uninjured side. Controlled active
      range of motion exercises can usually be started 3 to 4 weeks after the injury or
      open surgical repair, respectively. Protective splinting is continued until the
      sixth week and unrestricted use allowed 12 weeks following injury.

PMID- 7740250
TI  - [Characteristics of the diagnosis and treatment of venous thrombosis.
      Investigational strategies].

PMID- 7740251
TI  - [Medical treatment of deep venous thrombosis. Therapeutic measures in the acute
      stage].

PMID- 7740252
TI  - [Characteristics of the diagnosis and treatment of venous thrombosis. Biological
      monitoring of anticoagulant treatment].

PMID- 7740253
TI  - [Characteristics of the diagnosis and treatment of venous thrombosis. Benefit
      risk relationship of anticoagulant treatment].

PMID- 7740254
TI  - [Clinical problem: painful abdomen].

PMID- 7740249
TI  - Exercise, training and red blood cell turnover.
AB  - Endurance training can lead to what has been termed 'sports anaemia'. Although
      under normal conditions, red blood cells (RBCs) have a lifespan of about 120
      days, the rate of aging may increase during intensive training. However, RBC
      deficiency is rare in athletes, and sports anaemia is probably due to an expanded
      plasma volume. Cycling, running and swimming have been shown to cause RBC damage.
      While most investigators measure indices of haemolysis (for example, plasma
      haemoglobin or haptoglobin), RBC removal is normally an extravascular process
      that does not involve haemolysis. Attention is now turning to cellular indices
      (such as antioxidant depletion, or protein or lipid damage) that may be more
      indicative of exercise-induced damage. RBCs are vulnerable to oxidative damage
      because of their continuous exposure to oxygen and their high concentrations of
      polyunsaturated fatty acids and haem iron. As oxidative stress may be
      proportional to oxygen uptake, it is not surprising that antioxidants in muscle,
      liver and RBCs can be depleted during exercise. Oxidative damage to RBCs can also
      perturb ionic homeostasis and facilitate cellular dehydration. These changes
      impair RBC deformability which can, in turn, impede the passage of RBCs through
      the microcirculation. This may lead to hypoxia in working muscle during single
      episodes of exercise and possibly an increased rate of RBC destruction with long
      term exercise. Providing RBC destruction does not exceed the rate of RBC
      production, no detrimental effect to athletic performance should occur. An
      increased rate of RBC turnover may be advantageous because young cells are more
      efficient in transporting oxygen. Because most techniques examine the RBC
      population as a whole, more sophisticated methods which analyse cells
      individually are required to determine the mechanisms involved in exercise
      induced damage of RBCs.

PMID- 7740255
TI  - [The institutional psychiatrist: ethnopsychiatrist in spite of himself?].

PMID- 7740256
TI  - [The program "Youth and Health". A case-control evaluation of its effects on the
      health of pupils and high-school students in Vaud].

PMID- 7740257
TI  - [Arterial hypertension and primary hyperparathyroidism--a reversible condition?].

PMID- 7740258
TI  - [Control of friends and relatives (contact tracing) has been neglected in the
      case of HIV infections. Results of a 'look-back' study carried out in
      Switzerland].

PMID- 7740259
TI  - [Violence in the primary school environment].

PMID- 7740260
TI  - [Case history--red urine].

PMID- 7740261
TI  - [Contribution of bronchoalveolar lavage in immunosuppressed patients].
AB  - The safety of bronchoalveolar lavage has been greatly contributed to its
      widespread use in immunodepressed patients. This examination has changed the
      diagnostic approach to many lung diseases and often eliminates the need to open
      the thorax to make a lung biopsy. Bronchoalveolar lavage can be used to screen
      for a large number of diseases, particularly those due to infectious agents. In
      non-infectious diseases, the contribution of bronchoalveolar lavage is more
      limited. The impact of molecular biology techniques remains to be established.

PMID- 7740262
TI  - [Focus on the role of ventilation and ultraviolet rays in preventing nosocomial
      transmission of tuberculosis in health care facilities. Groupe de travail sur la
      prevention de la transmission nosocomiale de la tuberculose (Direction Generale
      de la Sante)].
AB  - Recent episodes of nosocomial tuberculosis, sometimes due to multiresistant
      strains, in HIV infected patients in the USA has led to the need for new
      prevention measures against the transmission of Mycobacterium tuberculosis in
      health care facilities. Tuberculosis is transmitted in Pflugge droplets generated
      when contagious persons cough. After drying, the droplets become aerosolized
      solid particles which are rapidly dispersed by air flow within the patient's
      room. People exposed to the same air are thus at high risk of being contaminated.
      If the air pressure in the patient's room is higher than the rest of the
      facility, the air coming form the room may contaminate personnel and other
      patients elsewhere in the facility. Infecting particles can be eliminated rapidly
      if the room air is ventilated outdoors. If the ventilation is strong enough so
      that air constantly circulates from the corridor into the room, infecting
      particles can no longer diffuse to the rest of the ward. It is also possible to
      use ultraviolet C light to disinfect the air, either within the room or within
      the ventilation system. These two basically simple systems are the fundamental
      environmental and prevention measures needed to limit tuberculosis spread in
      health care facilities. These methods are however technically complex, costly and
      require constant evaluation and maintenance by specialized personnel. In addition
      the potential side effects of ultraviolet waves could considerably reduce their
      application. These environmental methods, which are complementary methods, only
      have a meaning if the elementary measures for preventing the transmission of
      tuberculosis are correctly applied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740263
TI  - [Mechanical determinants of isotonic relaxation of the isolated diaphragmatic
      muscle].
AB  - The aim of this study was to define the mechanical determinants of isotonic
      relaxation of isolated diaphragm muscle in the rat over a load range (n = 30). We
      tested several hypotheses to determine the effect of i) load conditions (preload,
      post-load), ii) sudden changes in load during contraction, iii) length of the
      muscle at peak shortening, iv) maximal amplitude of shortening (delta L) and v)
      stimulation conditions on peak rate of isotonic reelongation (+dL/dmax). At
      tetanus at 30 Hz, +dL/dmax was linearly correlated to delta L peak shortening and
      total load. Variations in preload, peak shortening or postload did not modify the
      +dL/dmax vs delta L relationship but such variations did affected the
      relationships +dL/dmax vs total load or +dL/dmax vs peak shortening. For a given
      value of L, +dL/dmax was weaker for twitch than for tetanus. In conclusion, four
      findings show that over a wide lad range the maximal amplitude of shortening the
      main mechanical determinant of the rate of isotonic reelongation of the isolated
      diaphragm muscle, independently of the length of the muscle at peak shortening,
      the initial length of the muscle and independently of the load during
      reelongation.

PMID- 7740264
TI  - [Persistent left superior vena cava. Apropos of 2 cases].
AB  - Double superior vena cava with persistence of a left superior vena cava is rarely
      encountered. The prevalence in the general population is 0.3% but may reach 3 to
      10% in patients with inborn heart diseases. There are usually no clinical signs
      and the malformation is usually discovered fortuitiously. We describe the
      features of two cases observed in our institution and reviewed the literature on
      the subject.

PMID- 7740265
TI  - [Interstitial pneumonia and mitomycin C. Apropos of a case with analysis of the
      bronchoalveolar lavage].
AB  - Mitomycin C is an antibiotic used for its alkylizing effect in the treatment of
      broncogenic cancer. Haematologic, renal or pulmonary complications are sometimes
      severe. We report a case in a patient with poorly differentiated epidermoid
      bronchogenic carcinoma who developed clinical and radiological signs of bilateral
      infiltrating pneumonia due to mitomycine. This observation emphasizes the
      importance of bronchoalveolar lavage which implicated the immunological toxicity
      of mitomycine and explained the efficacity of corticosteroid treatment. Pulmonary
      lesions due to mitomycine were discussed.

PMID- 7740266
TI  - [Fibrosarcoma of mediastinal localization with cerebral metastasis].

PMID- 7740267
TI  - [Multiple nodular opacities in an asymptomatic patient].

PMID- 7740268
TI  - [Supra-, sub- or trans-diaphragmatic mass?].

PMID- 7740269
TI  - [A fleshy bud...].

PMID- 7740270
TI  - [Lifting and blepharoplasty].
AB  - The term face lifting enconpasses a variety of surgical procedures. Their goal is
      to obtain a rejuvenated look: frontal lift, temporal lift, cervico facial lift.
      The mask lift tends to a more radical modification of the upper third and mind
      third of the face. Its indications, with the psychological counterpart must be
      cautiously decided. The video endoscopy has recently modified and reduced the
      importance of the incision in frontal and mask lift. The blepharoplasties may be
      performed separately or, in combination with a face lift. The upper
      blepharoplasties rejunevate the look. The lower blepharoplasties are mostly
      indicated in baggy eyelids.

PMID- 7740271
TI  - [Rhinoplasty].
AB  - The goal of rhinoplasty should not be necessarily a small nose but a nose which
      is well balanced with the face and fits with the individual. Increasing number of
      patients is linked with improvement of the techniques and it is frequent to see
      patients asking for correction of minor defects. Sequelae of rhinoplasty are
      still frequent but less severe, and even if their correction is difficult, it is
      possible in most cases, thanks to the use of cartilage grafts and external
      approach.

PMID- 7740272
TI  - [Esthetic surgery of the breast].
AB  - The aesthetic surgery of the breast goes from one side to the other: make it
      bigger if it is too small, make it smaller if it is too big, tighten the skin if
      it falls. The situation is very complex because of the facts that these disgraces
      can be associated with different levels of severity, and that woman has two
      breasts each one often different from the other. But, if natural asymmetry is
      found so often, the surgeon should not reproduce it. Some problems cannot be
      solved yet: long time tolerance to the breast implants, unknowledge of the way
      the skin would heal, a very important factor for the reduction plasties. This
      surgery is a balance with two dishes: for example, the result that we are waiting
      for must not to be spoiled by a too big scar to obtain a small cosmetic benefit.
      The indications to operate should be given after they have been judged carefully
      and notified the patient very clearly about the advantages, inconveniences and
      expected complications.

PMID- 7740273
TI  - [Abdominal plasty and liposuction].
AB  - The changes in the abdomen due to pregnancy, aging and overweight are responsible
      for functional and aesthetic disorders. Aesthetic surgery is suitable in selected
      cases. The abdominal plasty procedures can be of long or limited extension
      depending on the case. Their purposes are to strength the muscle-aponeurose
      layers, take out the excess of fat and leave the skin with normal tension. These
      procedures make disappear the stretch marks only within the skin area that is
      excised. The liposuction has transformed these abdominal plasty procedures by
      diminishing the length of skin to be resected, and so, reducing the aesthetic
      disorder.

PMID- 7740274
TI  - [Breast cancer surgery].
AB  - Breast cancer surgery has gone through considerable modifications: lumpectomy and
      irradiation is now the treatment of choice for small tumors. Such conservatrice
      treatments can also be proposed in case of larger tumors, but one should keep in
      mind that they should leave a normal appearing breast, with no operative
      sequellae: breast remodelling is thus often necessary during the initial
      operative procedure. As more and more lesions are discovered by screening
      mammography, preoperative localization and rigorous surgical technique are
      required for proper diagnostic and treatment of such non palpable tumors. When a
      mastectomy is indicated, breast reconstruction can be systematically proposed,
      with no risk of interfering with follow-up: the development of breast implants,
      combined with continuous refinement of myocutaneous flaps, now allow a wide range
      of surgical techniques and predictable results, while the delay between
      mastectomy and breast reconstruction has been considerably reduced.

PMID- 7740275
TI  - [Surgery for sequelae of burns].
AB  - Burn injury remains one of the most devastating ordeal that a human being can
      sustain because of the function of the skin on vital and psychological levels.
      After-effects are mainly observed at cutaneous level as functional and
      aesthetically deformity contractures and may be linked with deeper lesions too.
      In most cases secondary surgical procedures are undertaken after stabilization of
      the inflammatory process but earlier surgery is needed in some cases because of
      problems encountered at ocular, mouth and neck levels mainly. All the
      possibilities of plastic surgery can be utilized. However in our practice Z
      plasties and skin grafts represent the basis of the burn reconstructive surgery
      while the more recent technique of tissue expansion has extended the part of
      local and regional flaps (but one should not use it as a routine method).

PMID- 7740276
TI  - [Deficiency anemia in infants. Diagnostic orientation].

PMID- 7740277
TI  - [Purulent meningitis. Epidemiology, etiology, diagnosis, development, prognosis,
      prevention, treatment].

PMID- 7740278
TI  - [Inflammation. Morphology, physiopathology].

PMID- 7740279
TI  - [Malignant tumors of the oropharynx. Epidemiology, diagnosis, treatment].

PMID- 7740280
TI  - [Malignant tumors of the rhinopharynx].

PMID- 7740281
TI  - [Hypothyroidism. Etiology, physiopathology, diagnosis, development, prognosis,
      treatment].

PMID- 7740282
TI  - [Urogenital gonococcus and Chlamydia infections (except Nicolas and Favre
      disease). Epidemiology, diagnosis, development, treatment].

PMID- 7740283
TI  - [Epithelial skin cancers].

PMID- 7740284
TI  - [Monitoring of patients in plaster casts].

PMID- 7740285
TI  - [Endoscopic papillotomy in benign biliary tract diseases: nature, frequency and
      severity of complications].
AB  - The purpose of this study was to evaluate the frequency, nature and significance
      of the complications of endoscopic sphincterotomy. Between 1989 and 1993
      endoscopic sphincterotomy was performed in 973 patients with benign affections of
      the bileducts. 398 patients were our own and 575 were admitted from other
      hospitals. The complications were recorded retrospectively on the basis of the
      discharge reports, which were available for each of our own patients (group A)
      and for 85% of the admitted patients (group B). Complications in all group A
      patients mentioned in the discharge reports were recorded and their clinical
      relevance was evaluated based on the patient records. Complications were
      mentioned in the reports of 82 (9.2%) of 887 cases and were more frequent in
      patients of group B (52 of 489: 10.6%) than in patients of group A (30 of 398:
      7.6%). Pancreatitis was mentioned significantly more frequent in group B (2.5% vs
      5.7%, p < 0.02). Reviewing the patient records of group A showed that clinically
      significant complications occurred in only 8 (2%) of 398 cases. The other
      complications mentioned in the discharge reports could not be confirmed or were
      without clinical significance. Hospitalization was short for these patients (5.3
      +/- 2.2 days), which points to the fact that the findings were insignificant. 2
      (0.2%) of 887 patients underwent surgery and 2 (0.2%) of 887 patients died due to
      a complication. These results clearly show that the complication rate determined
      on the basis of the discharge reports alone overestimates the true morbidity of
      the procedure. Often, an elevated amylase after ERCP/endoscopic sphincterotomy
      was erroneously interpreted as a pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740286
TI  - [Drug-induced pancreatitis: experience of the Swiss Drug Adverse Effects Center
      (SANZ) 1981-1993].
AB  - Acute pancreatitis may be caused by a number of different drugs. However, reports
      on the frequency of drug-related acute pancreatitis and on the drugs involved are
      rare. We therefore investigated all cases of drug-related acute pancreatitis
      which had been reported to the Swiss Drug Monitoring Center (Schweizerische
      Arzneimittel-Nebenwirkungszentrale, SANZ) between 1981 and 1993. During this
      period the total number of reported adverse drug reactions was 7338, 20 of which
      (0.3%) were considered to be probable cases of drug-related pancreatitis. In 18
      cases a single drug was incriminated, whereas in two cases two and four drugs
      respectively had to be investigated. Serious courses, deaths, or chronic
      pancreatitis were not reported. The most frequent single drugs incriminated were
      sulfonamide derivatives (5 cases), valproic acid (3 cases) and nonsteroidal anti
      flammatory drugs (2 cases). The frequencies reported here are consistent with the
      literature. Considering the total number of drugs prescribed, acute pancreatitis
      is a rare adverse drug reaction.

PMID- 7740287
TI  - [Abnormal increase in pancreatic polypeptide in the secretin-provocation test:
      hypoglycemia-induced?].
AB  - Pancreatic polypeptide (PP) can be used as a marker for endocrine active tumors
      originating from the pancreas. After intravenous administration of secretin,
      individually divergent increases in plasma PP concentration can be observed
      hampering interpretation of the stimulation test. Under certain circumstances
      elevated basal PP concentrations can be observed. Besides age, renal
      insufficiency and diabetes, hypoglycemia can cause high PP levels. We therefore
      inquired whether in patients with atypically high increase of PP after secretin
      this increase could be caused by hypoglycemia during the secretin stimulation
      test. In order to test this hypothesis we prospectively determined the plasma
      glucose and insulin concentrations in addition to the routinely measured gastro
      intestinal hormones in 19 patients referred for secretin provocation test. In the
      16 patients in whom the increase of PP was not due to an endocrine active tumor
      or renal insufficiency, PP rose to 170 +/- 57 pmol/l (+/- SEM) 2 minutes after
      secretin administration. In parallel, plasma insulin concentration increased to
      365 +/- 51 pmol/l 2 minutes after secretin. The maximal insulin concentrations
      correlated significantly with the PP concentrations observed at the same time (R
      = 0.73, p < 0.01). The mean glucose concentration, however, remained constantly
      between 4.8 +/- 0.3 and 5.2 +/- 0.3 mmol/l and there was no correlation between
      the peak plasma PP concentrations after secretin and the plasma glucose
      concentrations (R = 0.07). The minimal glucose concentrations observed were 3.3
      mmol/l in three patients (30 minutes after secretin in 2 patients and 45 minutes
      after secretin in one). The mean plasma glucagon concentration rose to 22.5 +/-
      4.1 pmol/l 10 minutes after secretin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740288
TI  - [Cephalic duodenopancreatectomy with pylorus preservation: for which patients?].
AB  - From 1984 to the end of 1993, we performed 51 duodenopancreatectomies with
      pylorus preservation (27 for chronic pancreatitis and 24 for tumours). We have a
      complete follow up for 96% of our patients with a mean range of 76 months in the
      first group and 33 months in the second. There was no per- or postoperative
      mortality and 15% immediate postoperative morbidity. We observed 5 cases (10%) of
      anastomotic ulceration. New surgical technics enabled us to avoid this major
      complication for our last 31 patients. The short and long term benefits of
      pylorus-preserving duodenopancreatectomy on patients' wellbeing, nutritional
      status and weight gain were confirmed in 22 patients (82%) with pancreatitis. The
      mean survival time in patients with tumors (periampullary and head of pancreas
      adenocarcinoma) is similar to that with the classical Whipple procedure.

PMID- 7740289
TI  - [Cephalic duodenopancreatectomy for pancreatic adenocarcinoma].
AB  - Cephalic duodenopancreatectomy is certainly the operation of choice in cases of
      adenocarcinoma of the pancreatic head. We evaluated the results of this operation
      in order to justify its indication and to pinpoint the factors that have an
      influence on the patients' prognosis after the operation. From 1982 to 1992, 386
      patients were hospitalized in our department with the diagnosis of pancreatic
      cancer, all histological types included. Of these, 21 men and 18 women, mean age
      65 years, underwent cephalic duodenopancreatectomy for adenocarcinoma. Associated
      with these operations were 3 liver metastasis excisions, 2 vascular resections, 1
      colectomy and 1 splenectomy. All the tumors were operated on whenever technically
      possible, except those associated with distant metastasis. Postoperatively, only
      one patient died (on the 29th day, of viral meningitis). Postoperative morbidity
      was 51% with 23% local complications. There was one leakage of the anastomosis.
      Age, weight loss, history of pancreatitis or cirrhosis, anesthetic risk (ASA) and
      tumor staging were not found to be factors increasing the risk of postoperative
      complications. Survival after 1 year was 34% and after 5 years 6%. The degree of
      histological differentiation was the only factor that had any significant
      influence on the postoperative survival rate in our study. We conclude that
      cephalic duodenopancreatectomy is the treatment of choice which is capable of
      improving the quality, and to a lesser extent the length, of survival of patients
      suffering from pancreatic cancer, with acceptable postoperative mortality and
      morbidity rates.

PMID- 7740290
TI  - [Significance of subtype pattern of antimitochondrial antibodies in primary
      biliary cirrhosis for prognostic parameters and response to ursodeoxycholic
      acid].
AB  - Antimitochondrial antibodies are of considerable importance for the diagnosis of
      primary biliary cirrhosis. Several subtypes of antimitochondrial antibodies have
      been identified and the pattern has been associated with prognosis of the disease
      in the long term course. 22 patients with primary biliary cirrhosis (19 female, 3
      male; age 29-66, mean 49 years) were examined for the occurrence of the subtypes
      of antimitochondrial antibodies anti M2, anti M4 and anti M9. Diagnosis of
      primary biliary cirrhosis was based on elevated cholestatic enzymes,
      antimitochondrial antibodies, histology and exclusion of other chronic liver
      disease in all patients and elevated serum IgM concentration in 18/22 patients.
      Most patients were included in a study protocol of the Swiss Association for the
      Study of the Liver and treated with 10 mg/kg/day oral ursodeoxycholic acid.
      According to the subtype pattern of antimitochondrial antibodies, patients were
      divided into 4 groups A to D (A: anti M2-, anti M4-, anti M9+; B: anti M2+, anti
      M4-, anti M9+; C: anti M2+, anti M4-, anti M9- and D: anti M2+, anti M4+, anti M9
      ). The groups were compared with respect to the prognostically relevant
      parameters age, bilirubin, albumin, prothrombin time and peripheral edema, as
      well as the occurrence of granulomas in liver biopsy, galactose elimination
      capacity and response to treatment with ursodeoxycholic acid during one year.
      Treatment response was expressed as decrease of the serum concentration of IgM,
      GPT, alkaline phosphatase, gamma glutamyl transpeptidase and bilirubin. No
      significant differences between the four groups were found with respect to the
      prognostically relevant parameters, histology and galactose elimination capacity
      at study entry.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740291
TI  - [Treatment of chronic virus hepatitis with acetylsalicylic acid].
AB  - The treatment of chronic hepatitis B and C with recombinant interferon (IFN) has
      only poor durable response rates. In the past only the lack of any prior
      effective therapy regimen could justify the use of this expensive agent. Dose
      escalating or prolonged treatment courses did not enhance the rate of sustained
      remissions. Pre- or cotreatment with antiviral (e.g. acyclovir, ribavirin,
      isoprenosin) or immunomodulating (e.g. prednisone, gamma IFN) drugs have not
      influenced the resistance to exogenous (IFN) of many patients. The mechanisms
      underlying resistance to this drug remain unknown. Some hypotheses focus on IFN
      antibodies, down regulation of IFN receptors or defects in the postreceptor
      response of cells to IFN. In 1991 Hannigan and Williams (Science 1991; 251: 204
      207) described a synergistic signal transduction effect in human fibroblasts
      after exposure to IFN. Arachidonic acid (AA) activation from membrane
      phospholipid pools is common to many receptors and can be followed by
      metabolization of AA by cyclooxygenase to prostanoids, thromboxanes and
      eicosanoids and by lipoxygenase to leukotrienes; inhibition of these AA oxidation
      pathways by addition of inhibitors of these enzymes (e.g. indomethacin) resulted
      in marked amplification of the IFN signal, possibly by using the epoxygenase
      enzyme family as an alternative pathway. Our data are taken from the pretreatment
      part of a current study for evaluation of pre- and combination treatment with
      acetylsalicylic acid (ASA) as cyclooxygenase inhibitor and IFN in chronic
      hepatitis C. 27 patients with histologically proven chronic active hepatitis C
      were divided into two groups. Group A (16 patients) were treated with a daily
      dose of 100 mg ASA orally, and the 11 patients in group B served as untreated
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740292
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). Medical
      Pharmaceutical District Society Bern. 2nd Winter meeting, 22 November 1910 in
      Hotel National. 1911].

PMID- 7740293
TI  - [Early and late results of the surgical treatment of left ventricular aneurysms;
      report of 105 patients].
AB  - This study determined perioperative mortality and morbidity and attempted to
      identify predictors of operative mortality and long-term outcome in a series of
      105 patients who underwent surgery for left ventricular aneurysm at this
      institution during a 7-year period. The main indications for treatment of
      ventricular aneurysm were angina, dyspnea, ventricular arrhythmias and systemic
      embolism. Overall mortality was 5.7% and 5-year survival 78%. Left ventricular
      systolic function, age, unstable angina and previous cardiac surgery were
      independent predictors of operative mortality and of long-term survival. Main
      complications observed were perioperative myocardial infarction, ventricular
      tachyarrhythmias and neurological, almost reversible defects. Although our
      experience with newer techniques such as patch plasty has been acquired in recent
      years, according to the literature the type of aneurysm repair seems not to be a
      strong predicator of operative mortality or improved long-term survival.
      Echocardiography provides important information concerning the extent of tissue
      resection needed and the ideal size of the patch. In patients with symptomatic
      coronary disease, complete revascularization should be attempted to allow
      recovery of adjacent myocardium after restoration of ventricular geometry. Repair
      of left ventricular aneurysm can be performed with acceptably low mortality by
      linear closure or by patch plasty technique. Remodelling the left ventricle using
      an endocardial patch has been found to fulfill its theoretical advantages in
      improving ventricular performance, by restoring the functional geometry of the
      heart. This operation can be performed with low perioperative risk and leads to a
      late functional improvement in the majority of patients.

PMID- 7740294
TI  - [Computer-supported patient history: a workplace analysis].
AB  - Since 1991, an extensive computer network has been developed and implemented at
      the Cantonal Hospital of Lucerne. The medical applications include computer aided
      management of patient charts, medical correspondence, and compilation of
      diagnosis statistics according to the ICD-9 code. In 1992, the system was
      introduced as a pilot project in the departments of pediatrics and pediatric
      surgery of the Lucerne Children's Hospital. This new system has been
      prospectively evaluated using a workplace analysis. The time taken to complete
      patient charts and surgical reports was recorded for 14 days before and after the
      introduction of the computerized system. This analysis was performed for both
      physicians and secretarial staff. The time delay between the discharge of the
      patient and the mailing of the discharge letter to the family doctor was also
      recorded. By conventional means, the average time for the physician to generate a
      patient chart (26 minutes, n = 119) was slightly lower than the time needed with
      the computer system (28 minutes, n = 177). However, for a discharge letter, the
      time needed by the physician was reduced by one third with the computer system
      and by more than one half for the secretarial staff (32 and 66 minutes
      conventionally; 22 and 24 minutes respectively with the computer system; p <
      0.0001). The time required for the generation of surgical reports was reduced
      from 17 to 13 minutes per patient and the processing time by secretaries from 37
      to 14 minutes. The time delay between the discharge of the patient and the
      mailing of the discharge letter was reduced by 50% from 7.6 to 3.9 days.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7740295
TI  - [Clinical value of a polymerase chain reaction on cytomegalovirus DNA in
      cerebrospinal fluid in HIV patients with neurological symptoms].
AB  - The value of the PCR for CMV in the CSF was evaluated. 23 samples from 20
      patients were examined for CMV DNA, of which 11 were positive and 12 were
      negative for CMV. The clinical spectrum of the patients with positive samples
      included encephalitis, encephalitis, and polyradiculopathy, or isolated
      polyradiculopathy. The main symptoms were fever, confusion, lethargy, cognitive
      disturbance, cranial neuropathy, weakness of the legs, and incontinence. The
      laboratory evaluation showed a low CD4 lymphocyte count, a slightly increased
      blood sedimentation rate and a large variation of CSF patterns. The CMV early
      antigen tests were negative in all cases. In 4 cases the neuroradiological
      examination was compatible with CMV infection. 8 patients were treated with
      ganciclovir or foscarnet. Improvement of symptoms was observed in 2 cases and
      stabilization in 2 others. However, the CMV infection was rapidly progressive and
      9 out of 10 patients died after a mean of 53 days after diagnosis.

PMID- 7740296
TI  - [Magnetic resonance imaging of lesions of the triangular carpal ligament].
AB  - The wrist is a complex anatomical joint which is frequently involved in daily
      activities and exposed to trauma and overuse. That is why chronic wrist pain
      syndrome can be somewhat difficult to assess and requires the use of several
      imaging modalities. Three-compartment arthrography is an invasive but well-known
      technique that can evaluate interosseous ligaments as well as the triangular
      fibrocartilage complex; however in recent years MRI has become an important
      diagnostic tool in imaging wrist injuries, particularly triangular fibrocartilage
      complex. Its overall accuracy in detecting triangular fibrocartilage complex
      tears varies from 80 to 95% according to several authors, and even if there is
      still some controversy about the imaging of the small interosseous ligaments, MRI
      can also depict some other associated lesions.

PMID- 7740297
TI  - [Diagnosis and course assessment of collagenoses and vasculitides].

PMID- 7740298
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly).1917].

PMID- 7740299
TI  - Alternate site testing in hospitals--place in the future?

PMID- 7740301
TI  - An algorithm for evaluating swollen extremities in a community hospital-
      recommendations and results.

PMID- 7740300
TI  - Idiopathic pulmonary hemosiderosis and alveolar hemorrhage syndrome: case report
      and review of the literature.
AB  - The presence of widespread hemorrhage from the microvasculature of the lung into
      the alveolar spaces defines what is called the "alveolar hemorrhage syndrome",
      which can occur in association with a wide variety of clinical disorders. The
      cardinal manifestations of this syndrome include: hemoptysis, unexplained anemia
      and diffuse alveolar infiltrates on chest roentgenograms. Since the pulmonary
      features are similar, the diagnosis usually depends on the clinical, laboratory
      and pathologic evaluations. Early diagnosis and treatment is crucial since the
      occurrence of pulmonary hemorrhage in this syndrome may represent a catastrophic
      event with fatal consequences. Idiopathic pulmonary hemosiderosis (IPH) has been
      identified as a cause of alveolar hemorrhage in a small number of cases, mainly
      by exclusion criteria. We report a case of a 70-year old man who presented with a
      40-year history of intermittent hemoptysis and bilateral upper lobes alveolar
      infiltrates proved to be secondary to idiopathic pulmonary hemosiderosis.
      Although the lung apices are frequently spared in IPH, they were the site of the
      infiltrates in our case. To our knowledge, our patient had the longest survival
      time ever reported in the literature in adult IPH. A brief review of some of the
      disorders commonly associated with alveolar hemorrhage is also presented.

PMID- 7740302
TI  - Vancomycin therapy: resistance and appropriate usage guidelines.

PMID- 7740303
TI  - Cancer-associated rheumatic disorders: clues to occult neoplasia.
AB  - Interest in the rheumatologic manifestations of cancer is related in part to
      practical considerations, ie, earlier cancer diagnosis is possible through
      enhanced awareness of cancer-associated rheumatic syndromes. The spectrum of
      rheumatic disorders associated with cancer includes over 30 conditions, including
      hypertrophic osteoarthropathy, polymyalgia rheumatica, palmar fasciitis with
      polyarthritis, most autoimmune connective tissue diseases, and the more recently
      described antiphospholipid syndrome. It is generally held that extensive search
      for occult malignancy in most rheumatologic disorders is not cost efficient and
      not recommended unless accompanied by specific findings suggestive of malignancy.
      The present article discusses the supplementary findings that may justify
      malignancy evaluation.

PMID- 7740304
TI  - Pulmonary involvement in rheumatoid arthritis.
AB  - Pulmonary involvement is one of the extra-articular manifestations of rheumatoid
      arthritis (RA) and includes pleurisy, parenchymal nodules, interstitial
      involvement, and airway disease. Rheumatoid pulmonary vasculitis is rare.
      Pulmonary disease also may be observed as a toxic event consequent to treatment
      for RA. Although RA is more common in women, rheumatoid lung disease occurs more
      frequently in men who have long-standing rheumatoid disease, positive rheumatoid
      factor and subcutaneous nodules. Pleural involvement, usually asymptomatic, is
      the most common manifestation of lung disease in RA and may occur concurrently
      with pulmonary nodulosis or interstitial disease. The clinical features and
      course of pulmonary fibrosis in RA are similar to those of idiopathic pulmonary
      fibrosis. Bronchiolitis obliterans organizing pneumonia (BOOP), which has been
      recently described in RA patients, has nonspecific clinical features. The
      histological patterns correspond to proliferative bronchiolitis in the airway and
      organizing pneumonia in the alveoli. Obstructive lung disease in RA includes
      obliterative bronchiolitis (OB) and bronchiectasis. OB is an acute illness
      characterized histologically by a constrictive bronchiolitis. It may be
      idiopathic or induced by D-penicillamine or intramuscular gold compounds.
      Methotrexate (MTX)-pneumonitis is an uncommon complication of MTX treatment. Its
      clinical presentation is not specific, and diagnosis must be made after exclusion
      of other causes of pulmonary diseases. It is uncertain if preexisting lung
      disease predisposes RA patients to MTX-pneumonitis. Treatment of lung disease in
      RA is empirical. Corticosteroids are usually administered and immunosuppressive
      drugs are often added when pulmonary disease progresses and/or steroid side
      effects appear.

PMID- 7740305
TI  - The molecular basis of reactive amyloidosis.
AB  - Reactive amyloidosis is a disease occurring in patients suffering from chronic
      infections, inflammation, and certain malignant conditions that are characterized
      by a considerable elevation of the acute phase reactant serum amyloid A (SAA). It
      is defined by the presence of extracellular deposits of fibrillar material
      containing amyloid A (AA) as its main component. AA is an 8.5-kd protein
      structurally identical to the NH2-terminal of the acute phase reactant SAA. SAA
      consists of a group of evolutionally conserved amphipathic proteins, encoded by a
      large number of genes and produced abundantly during inflammation, all suggesting
      an important role, probably of a neutralizing (anti-inflammatory) nature. An
      analysis of various aspects of SAA provides no clues to the mechanism of amyloid
      production, its occurrence in only selected individuals, and its preferential
      relationship to one isotype of SAA. Until more data is available, the present
      view on AA amyloidogenesis remains hypothetical.

PMID- 7740306
TI  - Clinicopathologic correlations of the antiphospholipid syndrome.
AB  - Since the original description and definition of the antiphospholipid syndrome
      (APS), a number of distinct clinical manifestations related to it have appeared
      in the literature. These include vascular obstruction of both veins and arteries,
      thrombus formation on the endocardium and its consequences, as well as a group of
      other conditions where vascular obstructive mechanisms are either incompletely
      understood or unproven, eg, chorea, avascular necrosis, and pulmonary
      hypertension. Single vessel (large/medium) involvement or multiple vascular
      occlusions may cause a wide variety of presentations. Any combination of vascular
      occlusive events may occur in the same individual, and the time interval between
      them also varies considerably from weeks to months or even years. Rapid
      chronological occlusive events occurring over days to weeks have been termed the
      "catastrophic" APS. Most of these complications may be ascribed to the
      hypercoagulable state of which antiphospholipid antibodies appear either to be
      "markers" or intimately connected with the highly complex coagulation mechanisms
      resulting in thrombotic occlusions.

PMID- 7740307
TI  - Vasculitis associated with antiphospholipid syndrome.
AB  - Several syndromes involving antiphospholipid antibodies have been described in
      the literature. Although the varied clinical manifestations have been well
      delineated, the vascular pathophysiology in patients with these antibodies
      remains unclear. Vascular damage is often described as a vasculopathy; however,
      several case reports have described an associated vasculitis. We report two
      patients with manifestations of antiphospholipid antibody syndrome (APLS) and
      concurrent vasculitis. The first patient, a 42-year-old man, presented with
      abdominal pain and fevers. The second patient, a 39-year-old man, presented with
      fever and testicular pain. Both were ultimately felt to have polyarteritis nodosa
      associated with APLS. Their complicated hospital courses and difficulties we
      encountered in diagnosing and treating them are discussed. The literature
      describing other cases of vasculitis associated with antiphospholipid antibody
      syndrome is reviewed. Whether the presence of antiphospholipid antibodies favors
      the development of vasculitis or vice versa is not clear. Further studies are
      needed to address this question and to determine optimal therapeutic regimens in
      these critically ill patients.

PMID- 7740308
TI  - Bone and joint manifestations of hypothyroidism.
AB  - Hypothyroidism is frequently accompanied by musculoskeletal manifestations
      ranging from myalgias and arthralgias to true myopathy and arthritis. A case is
      presented in which an arthropathic process in the hip was the isolated finding in
      a young man who was severely hypothyroid. Previous literature on bone and joint
      manifestations of hypothyroidism is reviewed, with emphasis on cases where such
      manifestations were the presenting symptoms of thyroid dysfunction. Most cases of
      arthropathic changes in adult-recognized hypothyroidism involved the knees and
      hands, while the hip and the epiphysis of the femoral head appear more commonly
      involved in children. Thyroid hormones have known effects at the cellular level
      on proliferation and differentiation of bone and cartilage. The hypothyroid state
      appears to induce abnormalities in these tissues, which result in such clinical
      manifestations as epiphyseal dysgenesis, aseptic necrosis, possibly crystal
      induced arthritis, and an arthropathy characterized by highly viscous
      noninflammatory joint effusions primarily affecting the knees, wrists, and hands.
      Neuropathic and myopathic symptoms accompanying hypothyroidism may manifest as
      joint region abnormalities when in fact there is no underlying arthropathy.

PMID- 7740309
TI  - Rheumatologic complications of vitamin A and retinoids.
AB  - Retinoids are synthetic derivatives of vitamin A. They are administered primarily
      for dermatological conditions, such as psoriasis, acne, and disorders of
      keratinization. Toxicity has proven a significant problem with long-term
      administration of the retinoids. Bone abnormalities mimicking seronegative
      spondyloarthropathy or diffuse idiopathic skeletal hyperostosis have been
      described in many cases, as well as other rheumatologic manifestations such as
      arthritis, myopathy, and vasculitis. These retinoid-related adverse effects are
      reviewed.

PMID- 7740310
TI  - Gestational trophoblastic disease: epidemiology.

PMID- 7740311
TI  - Genetic analysis of gestational trophoblastic disease: a review.

PMID- 7740312
TI  - Human chorionic gonadotropin: properties and assay methods.
AB  - Modern HCG assay methodology provides a level of sensitivity such that "HCG"
      immunoactivity in normal individuals or other unexplained low-level "HCG"
      measurements may be problematic. Two-site assays improve specificity for
      authentic HCG by selectively measuring intact hormone, and such measures
      correlate well with biological activity. In some cases, 125I has been replaced
      with nonradioisotopic labels without sacrificing sensitivity. On the negative
      side, such two-site assays will not reveal the presence of free subunit that may
      originate from trophoblastic tissue. Because free beta subunit appears in the
      sera of patients with GTD, monitoring intact HCG alone may pose a risk. Thus,
      some form of subunit monitoring by total-beta or free-beta assay is desirable. If
      the beta subunit/HCG ratio reflects the degree of trophoblastic cell
      differentiation and aggressiveness, a combination of specific whole molecule and
      free subunit measurements may provide the ideal monitoring for GTD.

PMID- 7740313
TI  - Imaging of gestational trophoblastic disease.

PMID- 7740314
TI  - Gestational trophoblastic disease: prognostic variables and staging.

PMID- 7740315
TI  - Hydatidiform mole: diagnosis and management.

PMID- 7740316
TI  - Prophylactic chemotherapy of complete molar pregnancy.

PMID- 7740317
TI  - Persistent nonmetastatic gestational trophoblastic disease.
AB  - The management of GTD has developed as a result of an accurate and sensitive
      serologic marker, effective chemotherapeutic agents, and the judicious treatment
      of patients with evidence of persistence. Treatment and intervention guidelines
      are well established and will lead to a successful outcome for nearly all
      patients. Reproductive potential can be preserved and chemotherapy toxicity has
      been made quite manageable in the minority of patients requiring its
      administration. However, as demonstrated in the patient whose case is presented,
      violation or deviation from these guidelines for monitoring and intervention can
      lead to the unnecessary sacrifice of reproductive capability and the
      administration of potentially toxic multiagent chemotherapy regimens.

PMID- 7740318
TI  - Low-risk metastatic gestational trophoblastic tumors.

PMID- 7740319
TI  - Identification and management of high-risk gestational trophoblastic disease.

PMID- 7740320
TI  - Reproductive performance of patients after gestational trophoblastic disease.

PMID- 7740321
TI  - Pathology of gestational trophoblastic disease.

PMID- 7740322
TI  - Management of malignant pleural effusions.
AB  - Malignant pleural effusions are a common complication of advanced cancer,
      particularly breast and lung cancers. Clinical algorithms for the diagnosis and
      management of malignant pleural effusions form a framework for the cost-effective
      provision of meaningful palliation. When the entire episode of care is
      considered, the optimal therapy for malignant pleural effusions appears to be
      tube thoracostomy followed by intrapleural bleomycin. Alternative strategies for
      the delivery of intrapleural therapy (eg, soft catheters) and new intrapleural
      agents currently are being compared with standard therapy.

PMID- 7740323
TI  - Alleviation of cytotoxic therapy-induced normal tissue damage.
AB  - Cytotoxic chemotherapy and radiation therapy damage normal body tissues,
      resulting in stomatitis, conjunctivitis, esophagitis, proctitis, and dermatitis.
      Pursuant to this, the North Central Cancer Treatment Group has developed a series
      of clinical trials designed to study antidotes for these pathologic processes.
      These trials have demonstrated clinically helpful therapies (eg, oral cryotherapy
      for decreasing mucositis induced by 5-fluorouracil) and also have demonstrated
      lack of benefit for other proposed treatments. Results from several ongoing
      clinical trials should become available in the near future.

PMID- 7740324
TI  - Supportive nutrition to prevent cachexia and improve quality of life.
AB  - Nutritional care of cancer patients should always be considered supportive,
      whether the oncologic aim is cure or palliation. The goals of nutritional care
      are to support nutritional status, body composition, functional status, and
      quality of life. Proactive nutritional assessment and early intervention are the
      cornerstones of success. Failure to address nutrition is associated with longer
      hospital stays, increased risk of complication and death, and higher health care
      costs. Supportive nutritional intervention mandates standardized, cost-efficient
      assessment and aggressive symptom management. The latter includes nutrition
      impact symptoms along the entire gastrointestinal tract, sensory changes,
      psychologic distress, pain, and anorexia. Components of pharmacologic and
      behavioral intervention are discussed in the context of supportive nutrition of
      the patient with cancer.

PMID- 7740325
TI  - Docetaxel (Taxotere): a highly active taxoid with manageable toxicity.

PMID- 7740326
TI  - Review of docetaxel (Taxotere), a highly active new agent for the treatment of
      metastatic breast cancer.
AB  - Phase II studies have demonstrated that docetaxel (Taxotere; Rhone-Poulenc Rorer,
      Collegeville, PA) is one of the most active single agents in the treatment of
      metastatic breast cancer. The overall response rate as front-line therapy for
      metastatic disease was 59% (95% confidence interval, 51% to 67%) in five phase II
      trials (four of which were multicenter) when 100 mg/m2 docetaxel was infused over
      1 hour every 3 weeks. In the three phase II trials reported to date of patients
      with metastatic cancer who had failed previous frontline therapy, 100 mg/m2
      docetaxel infused over 1 hour every 3 weeks produced an objective response rate
      of 49% (95% confidence interval, 40% to 58%). Two of these trials specifically
      included patients who had progressed while receiving either an anthracycline or
      an anthracenedione; the overall response rate in this subset of 83 patients was
      48%. The most significant acute toxicity noted in these trials was neutropenia.
      Grade 4 neutropenia occurred in the majority of patients but rarely resulted in
      treatment delays. Hypersensitivity reactions also were common in nonpremedicated
      patients, but were rare after the institution of premedication with
      antihistamines and/or glucocorticoids. A novel toxicity observed in many patients
      was fluid retention syndrome, with onset at a median of four to five cycles. The
      fluid retention was of noncardiac or renal origin, was slowly progressive with
      additional cycles of therapy, was reversible after cessation of the drug, and
      could be largely ameliorated by oral diuretics and glucocorticoid premedication.
      Phase III studies to further define docetaxel's role in the treatment of breast
      cancer are now under way.

PMID- 7740327
TI  - Summary of phase II data of docetaxel (Taxotere), an active agent in the first-
      and second-line treatment of advanced non-small cell lung cancer.
AB  - Six phase II studies have been conducted in the United States and Europe using
      docetaxel (Taxotere; Rhone-Poulenc Rorer, Antony, France) for advanced non-small
      cell lung cancer. One hundred eighty chemotherapy-naive patients in four studies
      and 88 patients who failed prior platinum-containing chemotherapy in two studies
      were treated with docetaxel 75 to 100 mg/m2 intravenously over 1 hour every 3
      weeks. Fifty-nine percent of patients had adenocarcinoma and 82% had stage IV
      disease. At a dose of 100 mg/m2, 30% of evaluable chemotherapy-naive patients
      (27% of the intent-to-treat population) and 20% of evaluable platinum
      refractory/resistant patients (17% of the intent-to-treat population) achieved a
      partial response; projected median survival is 9 months in both studies.
      Neutropenia was the primary dose-limiting acute side effect. Fluid retention,
      which occurred in patients who received multiple courses of treatment, was common
      but rarely dose-limiting, and may be ameliorated with prophylactic
      corticosteroids. Other toxic effects were relatively mild. Docetaxel has
      significant activity against advanced non-small cell lung cancer, producing a
      major response in both chemotherapy-naive patients and patients who had failed
      prior platinum-containing chemotherapy.

PMID- 7740328
TI  - Preclinical evaluation of docetaxel (Taxotere).
AB  - Progress in cancer chemotherapy has been made owing to the discovery and
      development of drugs that have new structures, new mechanisms of action, and high
      levels of experimental antitumor activity. Docetaxel (Taxotere; Rhone-Poulenc
      Rorer, Antony, France) is prepared by semisynthesis from 10-deacetyl baccatin
      III, an inactive taxoid precursor extracted from the needles of the European yew
      Taxus baccata. Docetaxel has been found to promote tubulin assembly in
      microtubules and to inhibit their depolymerization. As predicted by its unique
      biochemical mechanism of action, docetaxel acts as a mitotic spindle poison and
      induces a mitotic block in proliferating cells. In vitro, the docetaxel
      concentrations required to reduce murine and human cell survival by 50% range
      from 4 to 35 ng/mL, and the cytotoxic effects are greater on proliferating cells
      than on nonproliferating cells. Docetaxel also is cytotoxic at clinically
      relevant concentrations against fresh human tumor biopsy specimens (breast, lung,
      ovarian, colorectal cancer, melanoma) in a soft agar cloning system. Docetaxel
      has significant in vivo antitumor activity in the different models generally used
      for the preclinical evaluation of drugs. Eleven of 12 murine transplantable
      tumors in syngeneic mice have been found to be sensitive to intravenous docetaxel
      with complete regressions of advanced-stage tumors. Activity also has been
      observed with human tumor xenografts in nude mice at an advanced stage. In
      combination studies, synergism has been observed in vivo with 5-fluorouracil,
      cyclophosphamide, etoposide, vinorelbine, and methotrexate. Preclinical toxicity
      in mice and dogs has been evaluated by using one and five daily intravenous
      doses, respectively. The dog was found to be the more sensitive species. The dose
      limiting toxicities are hematologic and gastrointestinal in both species.
      Neurotoxicity also has been observed at high dosages in mice.

PMID- 7740329
TI  - Docetaxel (Taxotere) in the treatment of solid tumors other than breast and lung
      cancer.
AB  - Docetaxel (Taxotere; Rhone-Poulenc Rorer, Antony, France) has been widely studied
      in phase II trials in Europe and in the United States in a range of solid tumors.
      This review examines its activity in diseases other than breast and lung cancer
      (which are reviewed elsewhere in this supplement). Seventeen separate trials in
      eight tumor types have been reviewed, including almost 500 evaluable cases. All
      studies involved the same schedule, ie, docetaxel 100 mg/m2 given over 1 hour
      every 3 weeks. Significant activity has been seen in several diseases. Response
      rates in ovarian cancer range from 17% to 37% (according to extent of prior
      therapy); in gastric and pancreatic cancer, response rates of 26% and 29% have
      been reported, despite the fact that these diseases are notoriously resistant to
      chemotherapy. Other tumor types in which activity has been seen include head and
      neck cancer (32% response rate), melanoma (17%), and soft tissue sarcoma (18%).
      With regard to toxicity, a major feature has been the development of fluid
      retention and skin toxicity; efforts to ameliorate this with premedication are
      under way. For the future, trials will examine combination schedules and will
      also assess the drug's activity compared with paclitaxel. Current data suggest
      that it possesses antitumor efficacy that is at least as broad, and there are
      examples in which preliminary information indicates superiority.

PMID- 7740330
TI  - Vinorelbine (Navelbine) in the treatment of breast cancer: a summary.
AB  - One of the new agents intensively studied in the last decade for the treatment of
      metastatic breast cancer is vinorelbine (Navelbine; Burroughs Wellcome Co,
      Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France). This vinca
      alkaloid produces response rates comparable to other single agents in women with
      metastatic breast cancer and is associated with a nonhematologic toxicity profile
      that makes it particularly advantageous for palliative treatment. In vitro
      studies provide evidence of the decreased neurotoxicity of vinorelbine compared
      with other vinca alkaloids and clinical studies document the drug's favorable
      toxicity profile. Granulocytopenia, the dose-limiting toxicity of this agent, is
      transient and, at current recommended dose levels, seldom results in life
      threatening consequences. Results of a randomized clinical trial of intravenous
      vinorelbine show a similar or slightly improved effect on patient quality of life
      compared with intravenous melphalan (Alkeran; Burroughs Wellcome Co). Response
      rates in phase II trials of single-agent vinorelbine in women with previously
      untreated metastatic breast cancer range from approximately 30% to 60%. A number
      of studies are under way on the use of vinorelbine in combination with other
      agents commonly administered for the treatment of metastatic breast cancer. The
      low toxicity of vinorelbine makes it an attractive addition to several current
      combination regimens. Studies of increased dose intensity regimens of vinorelbine
      also are being actively pursued. Efforts to optimize the use of vinorelbine will
      hopefully lead to improved therapeutic options for the management of metastatic
      breast cancer.

PMID- 7740331
TI  - The Current Status of Vinorelbine (Navelbine) in Breast Cancer. Proceedings of a
      symposium. McLean, Virginia, April 28-May 1, 1994.

PMID- 7740332
TI  - Vinorelbine (Navelbine) in the treatment of breast cancer: the European
      experience.
AB  - Phase II studies of vinorelbine (Navelbine; Burroughs Wellcome Co, Research
      Triangle Park, NC; Pierre Fabre Medicament, Paris, France) have been conducted
      mainly at a dose of 30 mg/m2/wk, and this schedule has been used extensively in
      the treatment of advanced breast cancer. Vinorelbine used in a first-line setting
      as a single agent in 25 patients with previously untreated advanced metastatic
      breast cancer produced objective responses in 15 patients (60%) and complete
      responses (CR) in five (20%). A large multicenter study to assess the response
      rate by the main site of disease involvement included 145 assessable patients.
      The overall response rate was 41% (10 CRs and 50 partial responses: skin, 70%;
      lymph nodes, 67%; primary tumor, 56%; lungs, 33%; measurable bone, 27%; and
      liver, 23%). The median time to disease progression was 25 weeks and the median
      overall survival duration was 18 months. Neutropenia was the principal toxicity
      with grade 3/4 suppression noted; however, this was not accompanied by serious
      infection (incidence of grade 3/4 infection < 1%). Other grade 3/4 toxicity also
      was uncommon. Another phase II study included 50 patients assessable for toxicity
      and response. The overall response rate was 50% (2% CRs). In a salvage setting
      (second- and third-line treatment), 33 patients were treated with an overall
      response rate of 30% (two CRs). Rates of toxicity were no greater than in first
      line patients. The most notable results for combination vinorelbine therapy were
      with a schedule of vinorelbine 25 mg/m2 on days 1 and 8 and doxorubicin 50 mg/m2
      on day 1, with cycles repeated every 21 days. The overall response rate for the
      89 evaluable patients was 74% (19 [21%] CRs; 47 [53%] partial responses). These
      data indicate that vinorelbine is a highly active agent with a favorable toxicity
      profile in the treatment of breast cancer.

PMID- 7740333
TI  - Quality of life analyses from vinorelbine (Navelbine) clinical trials of women
      with metastatic breast cancer.
AB  - The effect of therapy on a patient's quality of life (QOL) is an important factor
      in choosing a treatment, especially when the primary intent of therapy is
      palliation of symptoms. An increasing recognition of the importance of QOL
      prompted inclusion of QOL assessments in a number of clinical trials of women
      with breast cancer. This report describes two clinical trials in which women with
      metastatic breast cancer were treated with intravenous (IV) vinorelbine
      (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre
      Medicament, Paris, France). In a randomized trial, IV vinorelbine was compared
      with IV melphalan (Alkeran; Burroughs Wellcome Co) as second- or third-line
      treatment in patients with anthracycline-refractory breast cancer. In a second,
      nonrandomized study, vinorelbine was used as first- or second-line treatment in
      patients who had not received doxorubicin previously. Both studies assessed the
      QOL dimensions of physical functioning, symptom status, role functioning, and
      global QOL. In the randomized trial, analyses of linear time trends indicated
      that patients treated with vinorelbine compared with patients receiving IV
      melphalan had better physical functioning throughout most of the study.
      Differences between the two treatment groups in other QOL dimensions were not
      significant. In the nonrandomized study, patients who received vinorelbine as
      first-line therapy had worse role functioning and somewhat worse physical
      functioning than those who received the drug as second-line treatment. Overall,
      these studies suggest that patients who receive IV vinorelbine treatment maintain
      a reasonable QOL and that this agent is comparable to or better in some respects
      than IV melphalan.

PMID- 7740334
TI  - Combined doxorubicin/vinorelbine (Navelbine) therapy in the treatment of advanced
      breast cancer.
AB  - A multicenter US study of the combination of doxorubicin (50 mg/m2 day 1) and
      vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre
      Fabre Medicament, Paris, France) (25 mg/m2 days 1 and 8) every 21 days examined
      the effects of this regimen as first-line chemotherapy in advanced breast cancer
      patients. Of the 62 patients enrolled in the study, 41 were completely evaluable
      for response and toxicity at the time of this analysis. The median patient age
      was 59 years. Prior therapy included hormone therapy (55%), adjuvant chemotherapy
      (40%), and radiotherapy (28%). Two hundred twelve courses of combined therapy
      were given. Toxicities included granulocytopenia (grade 4, 83%; grade 3, 12%),
      febrile neutropenia requiring hospitalization (three patients, 8%), septic death
      (one patient, 3%), thrombocytopenia (grade 3, 5%), stomatitis (grade 4, 5%),
      alopecia (grade 3, 15%), and nausea/vomiting (grade 3, 12%). One patient
      developed clinical congestive heart failure due to doxorubicin. The overall
      response rate for 58 patients evaluable for response was 57% (95% confidence
      interval: 45% to 69%): 16% of patients had complete responses (9 patients) and
      41% had partial responses (24 patients). Twenty-seven percent of patients had
      stable disease (16 patients). This regimen was well tolerated and had excellent
      patient acceptance.

PMID- 7740335
TI  - Combination chemotherapy with vinorelbine (Navelbine) and mitoxantrone for
      metastatic breast cancer: a review.
AB  - Trials establishing the safety and efficacy of single-agent vinorelbine
      (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre
      Medicament, Paris, France) as first- and second-line chemotherapy for metastatic
      breast cancer led to testing of the combination of vinorelbine and mitoxantrone.
      Three phase II clinical trials in Europe and South America, and one phase I trial
      in the United States have studied the effects of this combination on advanced
      breast cancer. In the two phase II trials that used vinorelbine and mitoxantrone
      only, response rates were 56% for patients who received the combination as first
      line therapy and 36% for those who were anthracycline resistant. A third phase II
      trial looked at the effects of a combination of mitoxantrone and vinorelbine plus
      ifosfamide with mesna in patients who had failed at least two prior chemotherapy
      regimens; a 41% response rate was noted. In the phase I trial, the combination of
      vinorelbine and mitoxantrone with prophylactic granulocyte colony-stimulating
      factors was explored. Further trials are needed to study the combination of
      vinorelbine and mitoxantrone.

PMID- 7740336
TI  - Pilot study of vinorelbine (Navelbine) and paclitaxel (Taxol) in patients with
      refractory breast cancer and lung cancer.
AB  - Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre
      Fabre Medicament, Paris, France) and paclitaxel (Taxol; Bristol-Myers Oncology,
      Princeton, NJ) as single-agent therapy exhibit good activity in breast and lung
      cancers. Concurrent administration of vinorelbine and paclitaxel achieves
      synergistic cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cells in
      vitro. Because these agents bind to distinct sites on tubulin and affect
      microtubules in opposite ways, a pilot study was conducted of the combination of
      vinorelbine and paclitaxel in patients with metastatic breast cancer or lung
      cancer who were refractory to first-line chemotherapy. Entry criteria included
      measurable disease, a Karnofsky performance status of > or = 70, adequate bone
      marrow reserve, adequate hepatic and renal functions, and no central nervous
      system metastasis. Seven patients entered the study (one with breast cancer and
      six with lung cancer; three men and four women, with an age range of 39 to 79
      years). The first three patients received vinorelbine 25 mg/m2 intravenously for
      5 to 10 minutes on days 1 and 8, and paclitaxel 90 mg/m2 intravenously over 3
      hours on day 1 after the administration of vinorelbine. Premedication prior to
      paclitaxel consisted of dexamethasone, cimetidine, and diphenhydramine. The
      subsequent four patients enrolled in the study received the identical dose of
      vinorelbine, but the paclitaxel dose was increased to 175 mg/m2 in the same
      sequence. Patients received granulocyte colony-stimulating factor 5 micrograms/kg
      subcutaneously from days 3 to 17 (except day 8) or until the absolute granulocyte
      count was 10,000/microL or higher. Preliminary results showed that one of the
      first three patients developed grade 4 neutropenia and grade 5 infection. In the
      subsequent four patients, there were two grade 3 and two grade 4 cases of
      neutropenia; leukopenic fever or infection did not occur. Two patients required
      red blood cell transfusions. Two patients developed grade 1 and one patient
      developed grade 2 peripheral neuropathy. Myalgia and fatigue were common but self
      limited. The one patient with breast cancer had a partial response; no response
      was noted in the lung cancer patients.

PMID- 7740337
TI  - Oral vinorelbine (Navelbine) in the treatment of advanced breast cancer.
AB  - Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre
      Fabre Medicament, Paris, France) has been formulated as a liquid-filled, soft
      gelatin capsule. Pharmacokinetic studies of this agent indicate that it has a
      large volume of distribution, a long terminal half-life, and a high clearance
      rate. The pharmacokinetics of vinorelbine are similar whether the drug is
      administered orally or intravenously. Oral vinorelbine has a low bioavailability,
      which may be due to a high first-pass effect. Preliminary results from two
      multicenter phase II trials of oral vinorelbine in patients with advanced breast
      cancer are presented. In one study of 98 advanced breast cancer patients aged 65
      years and older with limited prior therapy, the response rate of oral vinorelbine
      was 24% (complete response, 5%; partial response, 19%). In a study of 131 heavily
      pretreated patients with advanced breast cancer, the response rate of oral
      vinorelbine was 11% (complete response, 0%; partial response, 11%). In both
      studies, oral vinorelbine was generally well tolerated. As with intravenous
      administration, neutropenia is common and neuropathy is infrequent. In contrast
      to intravenous administration, nausea, vomiting, and diarrhea are common. Based
      on these preliminary results, further clinical investigation of oral vinorelbine
      is warranted.

PMID- 7740338
TI  - Future directions for vinorelbine (Navelbine).
AB  - Metastatic breast cancer is treated with sequential hormone therapy for hormone
      sensitive subgroups of patients, and combination chemotherapy for hormone
      refractory tumors. The judicious utilization of both hormonal therapy and
      chemotherapy results in palliation for the majority of patients with this
      disease. In recent years, several new, exciting cytotoxic agents have reached
      clinical development. Among these is vinorelbine (Navelbine; Burroughs Wellcome
      Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France), a new
      vinca alkaloid clearly of great interest. Vinorelbine administered as a single
      agent following the weekly intravenous route of administration resulted in major
      objective responses in 45% of patients. Even in patients previously exposed to
      standard chemotherapy, 20% to 30% achieved a major objective regression. Front
      line chemotherapy with vinorelbine associated with an anthracycline or 5
      fluorouracil resulted in remission rates and durations, as well as survival
      times, comparable to those achieved with standard combinations. Combinations
      containing vinorelbine are being introduced in the adjuvant and neoadjuvant
      settings. Furthermore, additional schedules of administration of vinorelbine are
      being explored, including dose intensification in single-agent and combination
      trials. Vinorelbine is an effective agent for the treatment of metastatic breast
      cancer, and represents a welcome addition to our treatment armamentarium.

PMID- 7740339
TI  - The measles epidemic.

PMID- 7740340
TI  - The recruitment of blood donors from the black population of South Africa.

PMID- 7740341
TI  - Reporting occupational disease.

PMID- 7740342
TI  - Technological advances in regional anaesthesia.

PMID- 7740343
TI  - Quality in health care.

PMID- 7740344
TI  - The South African Pilot Hospital Accreditation Programme. Part I. The process.

PMID- 7740345
TI  - Occupational Diseases in Mines and Works Amendment Act, 1993.

PMID- 7740346
TI  - Sound an alarm!

PMID- 7740347
TI  - Carriage of Haemophilus influenzae in Cape Town children.
AB  - Little is known about the epidemiology of Haemophilus influenzae infections in
      South Africa. This study was designed to determine the prevalence, serotype
      distribution, antimicrobial susceptibility pattern and effect of age and
      hospitalisation on the carriage of H. influenzae in 322 Cape Town children. The
      overall and type b specific carriage rates in normal children (N = 107) were
      45.8% and 4.7% respectively. The yield following nasopharyngeal culture was twice
      that following throat culture (P < 0.001). Children hospitalised with
      tuberculosis (N = 62) had significantly greater carriage rates, 66.1% and 37.1%
      respectively (P = 0.02). Institutionalised mentally handicapped children (N = 77)
      and children with tuberculosis attending an outpatient clinic (N = 76) had lower
      carriage rates (P < 0.02). Antimicrobial resistance was a major problem only in
      children hospitalised with tuberculosis (rifampicin 100%, penicillin 43.9%,
      erythromycin 85.4%, co-trimoxazole 82.9%). This universal resistance to
      rifampicin has not been reported previously. There was no difference in the mean
      age of children with positive or negative cultures, with the exception of those
      hospitalised with tuberculosis. In this group children infected with type b were
      much younger (mean 19.7 months) than those with other and non-typeable infections
      (32.1 months) and the non-infected (50.1 months) (P = 0.04). Duration of
      hospitalisation or outpatient therapy in the patients with tuberculosis did not
      influence carriage rates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740348
TI  - The first 100 kidney transplants from living related donors at Groote Schuur
      Hospital.
AB  - Improved results with cadaver kidney transplantation and the increase in the
      number of cadaver organs have caused the continued use of donor kidneys from
      living relatives to be questioned. In this analysis of our first 100 renal
      transplants involving a living related donor, the 5-year graft survival rate was
      70%. The 5-year graft survival rate for recipients of grafts from HLA-identical
      donors was 81%, as opposed to the 64% survival rate for grafts from one-haplotype
      donors. Recipients of grafts from one-haplotype-matched donors who received donor
      specific blood transfusions demonstrated better graft survival than those who
      were not transfused. This analysis demonstrates that the results of living
      related kidney transplantation are good, and suggests that donor-specific blood
      transfusions may be beneficial.

PMID- 7740349
TI  - Residual risk of transmission of HIV through blood transfusion in South Africa.
AB  - Despite the ongoing review of donor recruitment criteria by local blood
      transfusion services and the development of highly sensitive and specific testing
      for the presence of antibodies to HIV in blood and blood products, there remains
      a residue of HIV in donated blood. This is because of donors who are in the
      'window period' between acquisition of HIV and seroconversion, human errors and
      limits to the sensitivity and specificity of current tests. Data available from a
      national survey of HIV seroprevalence in South African blood donors allowed for
      the estimation of the number of units screened negative but likely to be infected
      with HIV. Assuming window periods of 4.8 and 14 weeks, a test sensitivity of
      99.9%, a specificity of 98.5% and a human error rate of 0.1%, the likely rate of
      HIV-infected blood in the South African blood transfusion supply ranges from 1.1
      to 3.9/100,000 units, with a likely estimate of 2.2/100,000 units. In the current
      South African blood transfusion setting, between 8.1 and 28.2 units of blood per
      annum will be HIV-positive with a likely estimate of 15.9 units. This corresponds
      to an odds ratio of between 1:90 909 and 1:25 641 units infected with HIV. These
      data are comparable with the risk in developed countries. The expected increase
      in the incidence and prevalence of HIV infection in all adult South African
      populations necessitates additional measures to ensure a blood supply which is as
      safe as possible. Some of these measures have already been taken by local blood
      transfusion services.

PMID- 7740350
TI  - The 1992 measles epidemic in Cape Town--a changing epidemiological pattern.
AB  - Over the last 6 years there has been a decline in the incidence of measles in
      Cape Town. However, during August 1992 an outbreak occurred, with cases reported
      at many schools in children presumably immunised. The objectives of this study
      were to characterise the epidemic in Cape Town and to determine possible reasons
      for the outbreak. The investigation consisted of two components--a description of
      the epidemic and an investigation of an outbreak at one primary school. Results
      indicate that during the last 4 months of the year, 757 cases were notified in
      Cape Town, compared with 144 in the first 8 months. The epidemic affected mainly
      white and coloured children over 5 years of age (P < 0.001). In contrast, during
      the period before the epidemic most cases occurred in black children and in those
      aged less than 1 year (P < 0.001). There was no significant increase in
      hospitalised cases. Investigation of the outbreak at one school revealed that the
      attack rate was 7.6% (25/329 children). Immunisation coverage (at least one dose
      of any measles vaccine) was 91% and vaccine efficacy was estimated to be 79% (95%
      CI 55-90); it was highest for monovalent measles (100%) and lowest for measles
      mumps-rubella (74%). The epidemiology of measles in Cape Town has thus changed as
      evinced in this epidemic, with an increase in the number of cases occurring in
      older, previously vaccinated children. The possible reasons for this include both
      primary and secondary vaccine failure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7740351
TI  - Missed opportunities for immunisation at hospitals in the western Cape--a
      reappraisal.
AB  - Immunisation practices were examined at 6 hospitals in the western Cape during
      the latter half of 1992 to determine whether these practices had improved
      subsequent to the February 1991 resolution of the Health Matters Committee (HMC)
      on immunisation in hospitals, and since a similar study was undertaken in 1990.
      Exit interviews were conducted with the escorts of all children aged 3-59 months
      who attended the study hospitals on the days designated for the study. In the
      second study, 88 of the 311 children studied (28.3%) were in need of immunisation
      on arrival, but only 12 of the 88 (13.6%) were immunised during the hospital
      visit. There was no evidence of an increase in requests to see children's Road-to
      Health cards (37.1% compared with 35.2% previously). The incidence of missed
      opportunities for measles immunisation in children aged 6-59 months remained
      unacceptably high (51.4% compared with 63.7% previously, when a strict definition
      was used; and 15.7% compared with 18.1% previously, when a lenient definition was
      used). Health authorities at all levels need to take urgent action to address the
      problem of missed opportunities for immunisation at hospitals.

PMID- 7740352
TI  - Would national health insurance improve equity and efficiency of health care in
      South Africa? Lessons from Asia and Latin America.
AB  - Arguments for and against national health insurance (NHI) for South Africa are
      illuminated by the experiences of other middle-income developing countries. In
      many Latin American and Asian countries the majority of their populations are
      covered by NHI, coverage having steadily increased over the last decade. Patterns
      of care under NHI tend to be inefficient--hospital-oriented, highly specialised
      and technical, with excessive investigation, surgery and medication, neglect of
      primary care and severe cost escalation. In some cases, however, urban primary
      care has been promoted through polyclinics and health maintenance organisations.
      Inequalities in funding, access and utilisation exist between the insured and
      uninsured, between strata of the insured, and between urban and rural areas.
      These inequalities have at times been ameliorated by expansion of coverage,
      subsidisation of poorer beneficiaries and initiation of programmes that extend
      care to rural areas. NHI can improve or impair efficiency and equity in health
      care, depending on structures and processes of revenue generation, payment and
      organisation of care. These depend in turn on how those likely to lose or gain
      from each option exercise their collective power.

PMID- 7740353
TI  - Third wave of asbestos-related disease from secondary use of asbestos. A case
      report from industry.
AB  - An occupational health survey conducted in a workshop in which asbestos cement
      was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5
      fibres per millilitre of air. Radiological changes suggestive of asbestos-related
      pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline
      features of asbestosis. The survey confirmed that uncontrolled and hazardous use
      of asbestos continues in industry despite public awareness of its dangers and the
      Asbestos Regulations of 1987.

PMID- 7740354
TI  - Compensation for occupational lung disease in non-mining industry.
AB  - The course from claim submission (by the National Centre for Occupational health
      (NCOH)) to compensation (by the Workmen's Compensation Commissioner (WCC)) in 56
      cases of occupational disease (OD) was traced. Success rates were determined and
      the procedural factors which affect claim outcomes isolated. Of note are the 22%
      of claims which remained unresolved 3 years after submission. The long latent
      period of ODs causes difficulty in obtaining the employer's corroborating
      documentation; this was found to be a major factor in the non-resolution of
      claims. Active intervention by the NCOH resulted in claim resolution for an
      additional 9%. These findings support the proposal that the WCC establish a
      network of access points for workers where assistance from trained staff is
      available. It is further recommended that the WCC accept substitutes for the
      employer's documentary proof in cases where this is unobtainable.

PMID- 7740355
TI  - Lethal exposure.

PMID- 7740357
TI  - A proliferation of surgeries.

PMID- 7740356
TI  - Dispensing doctors and prescribing pharmacists--whose benefit?

PMID- 7740358
TI  - The epidemiology of fatal childhood burns.

PMID- 7740359
TI  - Morality and AIDS.

PMID- 7740360
TI  - Alcohol use among Cape Peninsula adolescents.

PMID- 7740361
TI  - Management of large-scale disasters.

PMID- 7740362
TI  - Inappropriate antenatal care.

PMID- 7740363
TI  - South Africa needs a coordinated health manpower policy.

PMID- 7740364
TI  - Diagnosing tuberculous meningitis.

PMID- 7740365
TI  - Bacterial and tuberculous meningitis in Swaziland.

PMID- 7740366
TI  - Alternative medicine.

PMID- 7740367
TI  - Neonatal HIV infection.

PMID- 7740368
TI  - [Psychiatric motivation of disability to work].

PMID- 7740369
TI  - Adverse reaction to 10% lignocaine spray?

PMID- 7740370
TI  - A cancer control programme for South Africa.

PMID- 7740371
TI  - Recent advances in the management of acute leukaemia in adults.

PMID- 7740372
TI  - Cancer of the cervix--death by neglect.

PMID- 7740373
TI  - Health care reform in South Africa.

PMID- 7740374
TI  - Treatment of syphilis in HIV-infected individuals--more questions than answers?

PMID- 7740375
TI  - Health systems research and planning.

PMID- 7740376
TI  - Childhood cancer and nuclear installations.

PMID- 7740377
TI  - Evaluation of the 3-drug combination, Rifater, versus 4-drug therapy in the
      ambulatory treatment of tuberculosis in Cape Town.
AB  - The subjective impression among clinicians that the use of Rifater was causing
      delayed sputum conversion and increased drug resistance was tested in a
      prospective study. Adults in the Cape Town municipal area with a first episode of
      pulmonary tuberculosis were treated either with Rifater or a regimen consisting
      of isoniazid, rifampicin, pyrazinamide and ethambutol. All patients who took the
      treatment as prescribed (67 Rifater, 39 the 4-drug regimen) converted to a
      negative sputum culture by the time 90 doses had been taken. The rates of
      inadequate compliance and of side-effects were similar in the two groups. Drug
      sensitivity testing of bacteria cultured from pre-treatment sputum specimens
      revealed an overall primary resistance rate of 4.84% in the population studied,
      sufficiently low to preclude any necessity for routine pre-treatment drug
      sensitivity testing.

PMID- 7740378
TI  - Risk factors for the development of osteoporosis in a South African population. A
      prospective analysis.
AB  - Despite the vast number of risk factors that apparently predispose to the
      development of osteoporosis (OP), they have not been accurately identified and
      given relative priority. In order to analyse possible risk factors prospectively
      in a local patient population with overt OP (histomorphometrically confirmed and
      characterised) and compare it with an appropriately matched non-OP control group
      (with normal bone mass on dual-energy X-ray absorptiometry), a detailed general
      history, risk factor analysis, dietary history and anthropometric data were
      obtained from 56 OP and 125 non-OP subjects. In females a positive family history
      of OP (P = 0.002), a fair complexion (P = 0.009), lower body mass (P = 0.02) and
      height (P = 0.03), no breast-feeding of babies (P = 0.006), a history of smoking
      (P = 0.001) and fat distribution around the waist (P = 0.009) were identified as
      risk factors. In males lack of exercise (P = 0.008), a history of smoking (P =
      0.01), lower body mass (P = 0.04) and height (P = 0.04), a preference for salty
      food (P = 0.02) and fat distribution around the waist (P = 0.002) appeared to
      predispose. Dietary calcium, phosphorus, protein and caffeine intakes were
      similar in OP and control subjects, but alcohol consumption was clearly higher in
      both OP males (P = 0.001) and females (P = 0.01).

PMID- 7740379
TI  - Guidelines for the management of asthma in adults in South Africa. Part II. Acute
      asthma. Working Group of the South African Pulmonology Society.
AB  - The morbidity and mortality caused by asthma can be attributed to three factors:
      underassessment of severity, failure on the part of both patients and their
      medical attendants to initiate treatment promptly, and undertreatment of
      exacerbations. Moreover, most exacerbations can be prevented by use of
      appropriate long-term treatment (S Afr Med J 1992; 81: 319-322). The present
      guidelines are for the care of acute asthma ('asthma attacks') and are intended
      to encourage a uniform approach to the management of exacerbations, whether of
      rapid or gradual onset, mild or severe. They have been developed on the basis of
      the best available evidence on the efficacy and safety of asthma drugs, and
      efforts have been made to ensure that recommendations are cost-effective and
      affordable, and may with little modification be applied in all locations: the
      home (as initial self-management), the clinic with modest facilities, doctors'
      surgeries, emergency departments and hospitals. The guidelines stress (i)
      assessment of severity; (ii) recognition of risk; and (iii) stepwise treatment
      based upon these assessments. Primary therapies are the repeated use of high
      doses of beta 2-agonists and early introduction of corticosteroids. Specific
      goals of treatment are to: (i) relieve airway obstruction; (ii) relieve
      hypoxaemia; (iii) restore lung function to normal as rapidly as possible by
      reducing airway irritability; (iv) provide a suitable plan to avoid future
      relapse; and (v) provide a written plan of action to be followed early in future
      attacks. Simplified management schemes for different locations are provided as
      addenda for ease of reference.

PMID- 7740380
TI  - Monogenic primary hypercholesterolaemia in South Africa.
AB  - Familial hypercholesterolaemia (FH) and familial defective apolipoprotein B-100
      (FDB) are the two major causes of monogenic primary hypercholesterolaemia. In
      this review, FH and FDB are defined in relation to normal lipoprotein metabolism.
      In South Africa FH affects about 1% of Afrikaners, Jews and Indians, while FDB is
      probably a much rarer disorder. In Afrikaners, three 'founder' mutations are
      responsible for more than 80% of FH. The population genetics that created the
      exceptionally high frequency of FH and comparatively low frequency of FDB in
      various South African populations are described. The genetic organisation and
      itinerary of the normal low-density lipoprotein (LDL) receptor are reviewed, with
      particular emphasis on the structure-function relationships in the LDL receptor
      that have been clarified by the mutations found in South Africa. Finally, the
      clinical relevance of research into FH in South Africa is discussed.

PMID- 7740381
TI  - Histologically diagnosed cancers in South Africa, 1988.
AB  - The National Cancer Registry (NCR) collects information on cancer diagnoses via a
      nation-wide network of public and private pathology laboratories. In 1988, 45,570
      new laboratory-diagnosed cancer cases were reported to the NCR. Minimal age
      standardised registration rates for black, white, coloured and Asian males were
      112.2, 229.9, 192.2 and 91.6/100,000, respectively, and those for females 107.2,
      201.3 148.1 and 118.0. About 40% of cancers in females and 31.3% in males
      occurred in potentially economically active adults aged 15-54 years. The top five
      cancers in males were: (i) basal cell skin cancer; (ii) cancer of the prostate
      gland; (iii) cancer of the oesophagus; (iv) lung cancer; and (v) squamous cell
      skin cancer. In females they were: (i) cancer of the cervix; (ii) breast cancer;
      (iii) basal cell skin cancer; (iv) squamous cell skin cancer; and (v) cancer of
      the oesophagus. Despite under-reporting, a number of cancers, especially those of
      the oesophagus and cervix in blacks and skin cancers in whites, rank among the
      highest in the world. Moreover, 40.4% of the cancers in adult males (15-64 years)
      and 15.2% of those in adult females were associated with tobacco use.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7740382
TI  - Radiation therapy services in South Africa.
AB  - A survey of both private and public sector radiation therapy facilities in South
      Africa shows that they are available in only 7 major urban centres. About 20,000
      cases are treated yearly by 58 therapists and 190 therapy radiographers, with 37
      megavoltage and 24 X-ray machines. Brachytherapy, imaging and planning equipment
      is also inadequate. With limited epidemiological data it appears that less than
      50% of all patients appropriately treated with radiation therapy present for such
      treatment. Increased referrals from sub-Saharan Africa place further strains on
      the system.

PMID- 7740384
TI  - National cancer control programme.

PMID- 7740383
TI  - Stress and burnout in junior doctors.
AB  - Questionnaires were sent to doctors who had graduated 2 1/2 years previously from
      two English-medium universities in South Africa. Findings showed that 77.8% of
      doctors had experienced symptoms consistent with burnout since graduating.
      Incidence of burnout was found to be related to an inability to communicate
      freely with patients in their own language. Although those doctors who saw more
      than forty patients a day reported more burnout, the difference was not
      statistically significant. The highest incidence of burnout was among doctors
      working in day hospitals and clinics, followed by those in hospital posts.
      Doctors working in their own practices experienced least burnout. Sixty-three per
      cent of doctors felt that a support group would be helpful.

PMID- 7740385
TI  - Child abuse reporting system in the western Cape.

PMID- 7740386
TI  - Pharmacists and allergy skin testing.

PMID- 7740387
TI  - Margarine and coronary heart disease.

PMID- 7740388
TI  - Nitrous oxide for alcohol withdrawal and other psychiatric disorders.

PMID- 7740390
TI  - Standards in diagnostic radiology.

PMID- 7740389
TI  - Endometrial carcinoma after transcervical resection of the endometrium.

PMID- 7740392
TI  - Diving and hyperbaric medicine in South Africa.

PMID- 7740391
TI  - [Fluoxetine in perspective].

PMID- 7740393
TI  - Pseudoephedrine and imipramine for depression.

PMID- 7740394
TI  - Masquerading as major depression.

PMID- 7740395
TI  - Drugs in sport.

PMID- 7740396
TI  - Acute gastric dilatation.

PMID- 7740397
TI  - Anti-M antibody in pregnancy.

PMID- 7740398
TI  - Long-term follow-up of histoplasmosis.

PMID- 7740399
TI  - Transient diabetes of the newborn.

PMID- 7740400
TI  - Treatment of non-small-cell lung cancer by high-dose-rate intraluminal
      brachytherapy.

PMID- 7740401
TI  - Does tamoxifen induce endometrial hyperplasia, carcinoma and polyps?

PMID- 7740402
TI  - Seroprevalence of HTLV-I in Natal/KwaZulu.

PMID- 7740403
TI  - Radiation dosage in computed tomographic and X-ray pelvimetry.

PMID- 7740404
TI  - The baby and the bathwater.

PMID- 7740405
TI  - [Adjuvant chemotherapy in soft-tissue sarcomas?].
AB  - PURPOSE: Patients with high-grade soft-tissue sarcomas have a bad prognosis
      because of frequent generalisation especially with lung metastases. The question
      is if there is a chance to modify the prognosis of these high risk patients by
      any form of adjuvant chemotherapy. PATIENTS AND METHODS: Published randomised
      studies with a no-chemotherapy control arm are reviewed. The most important
      criteria are disease-free survival and especially overall survival. RESULTS AND
      CONCLUSIONS: Postoperative adjuvant chemotherapy for high-grade soft-tissue
      sarcomas is still investigational. This holds true for all localisations: e. g.
      extremities, head and neck, trunk. More clinical studies are needed to establish
      any indication for routine application of cytostatic drugs in this setting. Other
      experimental procedures are also not yet prepared for widespread use outside of
      clinical trials: pre-operative ("neoadjuvant") induction chemotherapy, regional
      perfusion with cytostatics (+/- hyperthermia) or externally applied deep regional
      tumor hyperthermia with systemic chemotherapy. From the actual knowledge it
      should be concluded that the uncontrolled adjuvant treatment of soft-tissue
      sarcomas with cytostatic drugs might provoke more risks of side effects than gain
      in survival.

PMID- 7740406
TI  - [The results of primary HDR-afterloading brachytherapy in corpus carcinoma].
AB  - PURPOSE: In general the results of radiotherapy are regarded to be inferior
      compared to those of surgery, when it comes to the treatment of endometrial
      carcinoma, but some patients are elderly and have multiple medical problems,
      which make them inoperable. The risk of intracavitary radium therapy, caused by
      immobilisation, can be reduced by the use of fractionated high-dose-rate
      afterloading brachytherapy. With this method there are only very few results
      reported. PATIENTS AND METHODS: Treatment results of HDR brachytherapy (4 to 5
      times 8.5 Gy, one-channel applicator, intracavitary and 1 to 2 times 7 Gy
      intravaginal) at the University Hospital Vienna were analysed retrospectively
      (actuarial method [Kaplan-Meier]) regarding overall survival and recurrence-free
      interval according to stage and histology. Over a period from April 1981 until
      December 1992 325 patients were treated by this technique alone or combined with
      external beam therapy. Two hundred and eighty patients could be evaluated.
      Staging based on clinical examination and fractionated curettage. RESULTS: Five
      year overall survival was 58.1%, in stage Ia 68.5%, stage Ib 49.9%, stage II
      48.7%, according to histopathologic grading 1 68.5%, grade 2 53.2%, grade 3
      37.5%. 64 patients developed a recurrence after a median of 13 months, 45 of
      those a local recurrence only, 6 a local recurrence with distant metastases, 6 a
      lymph node recurrence only and 7 patients distant metastases only. CONCLUSION:
      These results are at least comparable to those of intracavitary radium therapy
      and low-dose-rate afterloading techniques. Better local control rates should be
      obtained by the Heyman packing method using Norman-Simon applicators based on
      individualised brachytherapy treatment planning, which optimises dose
      distribution according to the target volume based on computerised imaging.

PMID- 7740408
TI  - [The prognosis of bilateral breast carcinoma compared to unilateral breast tumor.
      5- and 10-year follow-ups].
AB  - PURPOSE: A review of published data does not provide a certainty whether survival
      rates are comparable or worse in women with bilateral breast cancer versus
      patients with an unilateral tumor. Therefore results of therapy in one-sided and
      both-sided breast cancer were retrospectively analysed. PATIENTS AND METHODS: In
      a period from 1977 to 1982 (follow-up 5 to 12 years) 531 breast cancer patients
      with T1-4 N0-3 M0 tumors were treated with mastectomy (n = 416) and breast
      conserving therapy (n = 115). Postoperative radiotherapy was performed in all
      patients (50 Gy, 2 Gy/day 5 times/weekly; chest wall/breast and regional lymph
      nodes). Patients with positive lymph nodes received chemotherapy. Forty patients
      developed bilateral breast cancer (simultaneous n = 10, metachronous n = 30) that
      was treated by mastectomy (n = 28) and conservative surgery (n = 12),
      respectively, followed by radiotherapy in 26 women. RESULTS: Five- and 10-year
      survival was 74% and 56% in unilateral affected women. In 83% and 67% there were
      no metastases, respectively. Incidence of metastases was 27.9%. In bilateral
      breast cancer group survival rates were 85% and 59% and without evidence of
      metastases 87% and 60%, respectively. Distant disease was diagnosed in 35%.
      Differences between the 2 groups were statistically not significant. Whereas in
      time of follow-up 11% of unilateral cancer locally failed in bilateral cancer
      patients recurrences of the first and second tumor were seen in 20% and 10%,
      respectively. CONCLUSIONS: Survival of patients with bilateral breast cancer is
      not significantly decreased compared with unilateral disease although in patients
      with both-sided carcinoma local recurrences and metastases seem to occur more
      frequently.

PMID- 7740407
TI  - [The radiotherapy treatment of painful calcaneal spurs].
AB  - PURPOSE: Many patients attend orthopedic departments complaining of pain on the
      plantar aspect of the calcaneum. The symptoms may subside spontaneously, but
      often persist. Treatment is usually by local injection of a corticosteroid,
      orthopedic devices or other standard treatment. If these methods fail, X-ray
      treatment may be considered. The efficacy of radiotherapy of the calcaneal spur
      was evaluated. PATIENTS AND METHODS: From April 1981 through December 1991, 18
      patients with painful heel were irradiated mostly with the caesium or telecobalt
      unit, usually with a dose of 4 times 0.5 Gy. Among these patients, 12 could be
      followed up during a prolonged period on the basis of questionnaires. RESULTS:
      According to the categories of v. Pannewitz 17% of the patients were pain-free by
      the end of the treatment course, 22% showed marked improvement, 33% showed
      improvement and in 28% the pain was not influenced. Over an average of 41.5
      months 58% of the patients reported freedom from pain. CONCLUSIONS: Low-dose
      radiotherapy appears to relieve the painful heel syndrome in a high proportion of
      patients. The overall treatment risk appears to be very small. The mechanism of
      low-dose radiotherapy is unknown.

PMID- 7740409
TI  - [The radiobiological aspects in the blocking of sensitive structures from the
      irradiation field].
AB  - BACKGROUND: In some cases the total dose has to be reduced in a section of an
      irradiation field by means of a transmission block. This can be performed in 2
      different ways: 1. A part of the planned fractions is blocked. 2. The dose of
      each fraction is reduced using a transmission block (transmission < 100%).
      METHOD: For both methods the biological tumor and normal tissue doses were
      calculated using the linear-quadratic model. A clinical case is discussed. RESULT
      AND CONCLUSION: With transmission blocks a therapeutic gain can be obtained.

PMID- 7740410
TI  - Reoxygenation of hypoxic cells by tumor shrinkage during irradiation. A computer
      simulation.
AB  - PURPOSE: A 3-dimensional computer simulation was developed in order to estimate
      the impact of tumor shrinkage on reoxygenation of chronic hypoxic tumor cells
      during a full course of fractionated irradiation. MATERIAL AND METHODS: The
      growth of a small tumor situated in a vascularized stroma with 350 capillary
      cross-sections/mm3 which were displaced by the growing tumor was simulated.
      Tumors contained 10(4) cells when irradiation started, intrinsic radiosensitivity
      was set to either low (alpha = 0.3 Gy-1, beta = 0.03 Gy-2) or high (alpha = 0.4
      Gy-1, beta = 0.04 Gy-2) values. Oxygen enhancement ratio was 3.0, potential tumor
      doubling time Tpot = 1.2 or 5 days. A simulated fractionated radiotherapy was
      carried out with daily fractions of 2.0 Gy, total dose 50 to 70 Gy. The presence
      or absence of factors preventing tumor cord shrinkage was also included. RESULTS:
      During the growth phase, all tumors developed a necrotic core with a hypoxic cell
      fraction of 25% under these conditions. During irradiation, the slower growing
      tumors (Tpot = 2 to 5 days) showed complete reoxygenation of the hypoxic cells
      after 30 to 40 Gy independent from radiosensitivity, undisturbed tumor shrinkage
      provided. If shrinkage was prevented, the hypoxic fraction rose to 100% after 30
      to 50 Gy. Local tumor control, defined as the destruction of all clonogenic and
      hypoxic tumor cells increased by 20 to 100% due to reoxygenation and 50 Gy were
      enough in order to sterilize the tumors in these cases. In the fast growing
      tumors (Tpot = 1 day), reoxygenation was only observed in the case of high
      radiosensitivity and undisturbed tumor shrinkage. In these tumors reoxygenation
      increased the control rates by up to 60%. CONCLUSION: The simulation results
      suggests that shrinking of a homogeneous tumor during irradiation with
      restoration of the normal vascular architecture can contribute significantly to
      reoxygenation, which in turn has a major effect on tumor control.

PMID- 7740411
TI  - [Dosage inhomogeneities in the matching of opposing photon fields and electron
      fields in head-neck tumors ].
AB  - PURPOSE: Head and neck tumors are often treated by a multiple-field technique,
      using a combination of opposing photon fields and electron beams in order to stay
      within the limit of the myelon tolerance dose. Dose inhomogeneities at field
      margins must be minimalized to avoid an increased rate of local recurrences or
      late complications. METHODS: A polystyrene phantom with a base of 12 x 16 cm was
      used to investigate the optimal conditions of field matching, using 9 MV photon
      beams and 8 to 10 MeV electron beams. The evaluation was performed by using an
      automatic video-densitometer and digital image processing. Dose distributions are
      presented as 3-dimensional plots and as dose profiles in a depth of 1.2 and 2.5
      cm. RESULTS: In the neck region photon and electron fields cannot exceed a field
      width of 6 to 7 cm. With unmodified electron fields and opposing photon fields
      with a 5 mm penumbra optimal geometrical matching is achieved by using an overlap
      of 2 mm referring to the field margins. Related to a reference dose of 100% the
      dose in 1.2 and 2.5 cm depth varied between 90% and 115%. Geometrical variations
      at the field margins, using a gap of 3 mm or an overlap of 5 mm, result in a
      local underdosage of 75 to 80%, respectively an overdosage of 135 to 150%
      referring to the reference dose. This dose inhomogeneity occurs at a width of 1
      cm around the field margins. CONCLUSIONS: Regarding clinical and physical aspects
      the matching of unmodified beams seems to have an advantage compared to the
      matching of fields with broadened penumbras. For the treatment of patients an
      immobilisation technique and a precise daily set up is required.

PMID- 7740412
TI  - [Comparative voice results after laser resection or irradiation of T1 vocal cord
      carcinoma].

PMID- 7740413
TI  - [Carcinoma in situ of the urinary bladder].

PMID- 7740414
TI  - [Late effects of hyperfractionated radiotherapy for advanced head and neck
      cancer: long-term follow-up results of RTOG 83-13. Radiation Therapy Oncology
      Group].

PMID- 7740415
TI  - [Neurological and cognitive impairment in long-term survivors of small cell lung
      cancer].

PMID- 7740416
TI  - [Medulloblastoma in very young children: outcome of definitive craniospinal
      irradiation following incomplete response to chemotherapy].

PMID- 7740417
TI  - How should polypoid lesions of the gallbladder be treated in the era of
      laparoscopic cholecystectomy?
AB  - BACKGROUND: Definitive criteria for choosing the most appropriate treatment for
      each type of polypoid lesion of the gallbladder (PLG) have yet to be established.
      METHODS: The shapes, sizes, echo patterns, and echogenicities of PLGs that had
      been evaluated by means of ultrasonography in 72 patients who had undergone
      resective surgery were analyzed retrospectively to elucidate the ultrasonic
      characteristics of polypoid cancers and to establish criteria for selecting the
      most suitable treatment such as laparoscopic cholecystectomy for each type of
      PLG. RESULTS: Histologic examinations showed cholesterol polyps in 47 patients,
      adenomas in 8, cancers in 16, and an inflammatory polyp in 1. The diameters of
      61% of the benign PLGs were less than 10 mm, whereas those of 88% of the cancers
      were more than 10 mm; 80% of the former were pedunculated and 56% of the latter
      were sessile. Seven of eight early-stage cancers had diameters less than 18 mm,
      whereas those of all eight more advanced cancers were greater than 18 mm. Five of
      the eight early-stage cancers were pedunculated, and six of the eight more
      advanced cancers were sessile. Cholecystectomy with or without full-thickness
      dissection were main surgical procedures used to resect benign PLGs and early
      stage cancers, whereas cholecystectomy with partial liver resection was used for
      more advanced cancers. Laparoscopic cholecystectomy was performed in the recent
      34 patients, four of whom had early-stage cancers. CONCLUSIONS: A PLG with a
      diameter of less than 18 mm is a potential early-stage cancer and therefore can
      be resected by laparoscopic cholecystectomy with full-thickness dissection.
      However, when cancer invades the subserosal layer or beyond, a second-look
      operation is necessary. A PLG with a diameter of greater than 18 mm may be an
      advanced cancer and should be removed by using cholecystectomy with partial liver
      resection or a more extended procedure with lymph node dissection.

PMID- 7740418
TI  - Role of cirrhosis in the hemodynamic response to hemorrhage in portal
      hypertension.
AB  - BACKGROUND: We studied hemodynamic alterations in normal and three models of
      portal hypertension at rest, after hemorrhage, and after resuscitation to
      determine the role of hepatic dysfunction in the splanchnic vascular response to
      hemorrhage in portal hypertension. METHODS: One noncirrhotic and two cirrhotic
      models of portal hypertension were produced in rabbits: partial prehepatic portal
      vein ligation, common bile duct ligation, and carbon tetrachloride-induced
      cirrhosis. Animals were subjected to isovolemic hemorrhage followed by reinfusion
      of shed blood. Portal, central, and aortic pressures, superior mesenteric artery
      blood flow, and portosystemic shunt were measured. RESULTS: Histologic
      examination showed parenchymal damage was absent in normal and portal vein
      ligation, severe in common bile duct ligation, and moderate in carbon
      tetrachloride-induced cirrhosis. All portal hypertensive animals exhibited
      diminished splanchnic vasoconstrictive response to hemorrhage compared with
      normal. The carbon tetrachloride cirrhosis group had severe cirrhotic changes,
      minimal portosystemic shunt, and mildly diminished constrictive response. In
      contrast, the portal vein ligation and common bile duct ligation animals had
      larger portosystemic shunts, markedly diminished constrictive response, and less
      severe parenchymal damage. A direct correlation existed between magnitude of rise
      in portal venous pressure or degree of portosystemic shunt and the fall in
      mesenteric resistance or diminution of vasoconstrictive response to hemorrhage.
      CONCLUSIONS: We concluded that the abnormal splanchnic vascular response in
      portal hypertension is relatively independent of the degree of hepatic
      parenchymal injury, but it is related to the degree of portal hypertension and
      possibly to splanchnic hyperemia.

PMID- 7740419
TI  - Acute abdomen in the hemodialysis patient population.
AB  - BACKGROUND: The cause and frequency of the acute abdomen in patients undergoing
      hemodialysis are not well reported. Previous studies associate bowel infarction
      with hemodialysis, but dialysis generally is not implicated as a risk factor for
      mesenteric ischemia. METHODS: The records of 567 patients undergoing long-term
      hemodialysis during the period from July 1988 to June 1993 were retrospectively
      reviewed. RESULTS: Twelve patients (2.1% of the hemodialysis population) were
      admitted with acute abdominal pain or sepsis. They were demographically no
      different than their counterparts who did not have an acute abdomen. The final
      diagnoses were bowel infarction in 11 patients and acute pancreatitis in one.
      Principal areas of involvement were equally divided between large and small
      intestine and were due to nonocclusive mesenteric ischemia in all cases. Six
      patients had an occluded hemodialysis fistula on admission, suggesting
      hypotension and/or hypovolemia as a possible etiologic factor. Overall, mortality
      and major morbidity rates were 50% and 25%, respectively. CONCLUSIONS: An acute
      abdomen is a relatively uncommon problem in the hemodialysis population but is
      associated with a high mortality. Mesenteric infarction is the most common cause
      and should be the presumptive diagnosis until proven otherwise.

PMID- 7740420
TI  - Mesocaval shunt or repeated sclerotherapy: effects on rebleeding and
      encephalopathy--a randomized trial.
AB  - BACKGROUND: Sclerotherapy is usually effective in controlling acutely bleeding
      esophageal varices. It may not be as effective as shunt surgery for prevention of
      rebleeding; therefore we undertook a prospective study comparing interposition
      mesocaval shunt (MCS) and repeated sclerotherapy. METHODS: Forty-five patients
      (mean age, 52.6 +/- 9.8 years) with variceal bleeding were randomized after
      emergency endoscopic sclerotherapy either to repeat variceal obliteration
      followed by regular check endoscopy (n = 21) or to elective interposition
      mesocaval shunting by use of 14 mm polytetrafluoroethylene graft (n = 24). There
      was an equal distribution of Child's classes in the two groups. RESULTS: In the
      sclerotherapy group 12 patients had recurrent hemorrhages causing five deaths
      compared with the shunt group, in which four patients had postoperative bleeding
      but without associated death. No difference was noted in the incidence of
      encephalopathy despite the development of total shunting 1 year after MCS. The
      median hospital stay was similar; 34.5 days (MCS) and 33 days (sclerotherapy).
      The number of intensive care unit days was also similar in the two groups. No
      difference was noted in survival in patients with Child's A and Child's B disease
      in the treatment groups. In patients with Child's C cirrhosis there was a
      statistically significant longer survival in patients undergoing MCS compared
      with patients undergoing sclerotherapy. CONCLUSIONS: The results of the study
      show that the rate of rebleeding is significantly higher after sclerotherapy than
      after mesocaval shunting. In patients with Child's C cirrhosis MCS may be an
      alternative to sclerotherapy for the prevention of rebleeding from esophageal
      varices in patients not suitable for transplantation.

PMID- 7740421
TI  - Surgical sepsis: constancy of antibiotic susceptibility of causative organisms.
AB  - BACKGROUND: It is well documented that antibiotic therapy exerts selective
      pressure on bacteria. Conversion of bacteria from susceptible to resistant to
      antibiotics has been observed often during antimicrobial therapy. It has been
      postulated that human intestinal reservoirs facilitate communication of
      transposons that can transfer resistance determinants among various bacterial
      species. METHODS: This study examined the susceptibilities of organisms isolated
      from infected abdomens to a number of antibiotic agents during a 12-year time
      interval. Analysis included 1102 isolates recovered from 255 specimens,
      representing the following genera: Bacteroides, Clostridium, Gemella,
      Fusobacterium, Peptostreptococcus, Porphyromonas, Prevotella, Enterococcus,
      Staphylococcus, Streptococcus, Pseudomonas, and Enterobacteriaceae. Strains were
      tested against beta-lactam agents, beta-lactams in combination with beta
      lactamase inhibitors, first, second, and third generation cephalosporins,
      aminoglycosides, clindamycin, metronidazole, chloramphenicol, and imipenem.
      RESULTS: The results indicated that during a time period of more than a decade
      essentially no change occurred in the antibiotic susceptible fraction of all
      species tested. CONCLUSIONS: Abdominal sepsis is caused by leakage of endogenous
      intestinal flora. This study suggests that the intestinal flora is not
      permanently affected by short-term antibiotic therapy and that older antibiotics
      are appropriate first-line therapeutic agents for community-acquired infections
      caused by normal intestinal flora.

PMID- 7740422
TI  - Clinical pilot study on high-dose intraarterial chemotherapy with direct
      hemoperfusion under hepatic venous isolation in patients with advanced
      hepatocellular carcinoma.
AB  - BACKGROUND: We recently developed a novel system of direct hemoperfusion under
      hepatic venous isolation in an attempt to achieve high-dose intraarterial
      chemotherapy for patients with malignant liver tumors. We report here the results
      of treatment of these patients with advanced hepatocellular carcinoma. METHODS:
      Adriamycin (100 to 150 mg/m2) was administered into the hepatic artery of 15
      patients, under conditions of extracorporeal drug elimination by direct
      hemoperfusion under hepatic venous isolation. Hepatic venous isolation was
      accomplished mainly by the double-balloon technique with an occlusion catheter
      and a balloon catheter. The isolated hepatic venous blood was filtered by direct
      hemoperfusion and pumped to the left axillary vein. RESULTS: During 5 minutes of
      adriamycin infusion, the mean drug extraction ratios of the direct hemoperfusion
      filters were 91% +/- 9% (mean +/- SD). The amount of drug removed by the system
      was 26.4% +/- 16.0% of the amount of drug administered. Two patients died, one of
      necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both
      deaths were related directly to the hepatic arterial catheter. Other side effects
      included hemolysis related to the system of hemoperfusion (87%), chemical
      hepatitis (80%), leukopenia less than 3000/mm3 (67%), alopecia (33%), and nausea
      and vomiting (20%). Nine (64%) of 14 evaluable patients had objective tumor
      responses, with a median duration of response of 6.2 months. CONCLUSIONS: This
      approach offers an effective therapeutic option for patients with advanced
      hepatocellular carcinoma.

PMID- 7740423
TI  - Hepatic metabolic response to injury and sepsis.
AB  - BACKGROUND: Experimental reports have indicated that hepatic oxidative and
      synthetic metabolism may become depressed in sepsis. Because the mechanism of
      infection-related liver dysfunction has not been established, further study of
      these functional alterations could contribute to the therapeutic management of
      septic organ failure syndromes. However, recently controversy has arisen over the
      existence of these derangements that must be reconciled before further progress
      in this field can be made. METHODS: Splanchnic balance studies for the
      measurement of glucose output and oxygen consumption were used to assess hepatic
      function in fasted normal volunteers (n = 18), injured patients (n = 10), and
      patients with sepsis (n = 18). The liver's contribution to splanchnic metabolism
      was estimated from a comparison of splanchnic oxygen utilization in response to
      increases in the liver-specific process of glucogenesis. In addition, in vivo
      liver albumin production was determined by using the [14C] carbonate technique.
      RESULTS: Glucose output after injury and sepsis was increased by 12.8% and 76.6%,
      respectively, compared with controls. On the basis of substrate balance studies,
      gluconeogenesis was estimated to account for 46%, 87%, and 93%, respectively, of
      splanchnic glucose output in each of the three groups. In patients with sepsis
      glucose output was also noted to be linearly related to regional oxygen
      consumption, indicating that these processes were coupled and increases in the
      respiratory activity of the splanchnic cellular mass could be accounted for by
      increases in new glucose output and gluconeogenic substrate clearance. The mean
      albumin synthetic rate increased during injury and sepsis by 22% and 29%,
      respectively, compared with normal volunteers. CONCLUSIONS: These studies cast
      doubt on the commonly held notion that tissue respiratory dysfunction may occur
      during sepsis. On the contrary, hepatic function is accelerated during
      hyperdynamic sepsis, and evidence indicating oxidative or synthetic functional
      depression is lacking.

PMID- 7740424
TI  - Effects of transection and reanastomosis on postprandial jejunal transit and
      contractile activity.
AB  - BACKGROUND: The purpose of this study was to determine how transection and
      reanastomosis of the intestinal wall influences postprandial motor activity and
      transit in the small intestine. METHODS: Six dogs were each instrumented with 12
      strain gauge transducers, two collection cannulas, and an infusion catheter
      defining a 100 cm study segment in the midjejunum. The animals underwent baseline
      measurements of postprandial motor activity and transit rate after 650 kcal solid
      and liquid meals. Postprandial motor activity was analyzed by computer methods
      that identify frequency, duration, amplitude, and propagation behavior of smooth
      muscle contractions. After the baseline measurements were performed, each animal
      underwent transection and reanastomosis of the intestinal wall at sites marked
      during the initial laparotomy. Measurements of postprandial motor activity and
      transit were repeated and compared with control values. RESULTS: Transection
      decreased frequency, amplitude, and percent propagation for postprandial
      contractions. Total propagating area per minute significantly decreased from 382
      +/- 20 gram-seconds/minute to 190 +/- 66 gram-seconds/minute after transection (p
      < 0.05). Intestinal transit decreased from 13.5 +/- 1.5 cm/min to 8.5 +/- 2.4
      cm/min (p < 0.05). The change in transit was related primarily to a change in
      frequency of propagating contractions (r = 0.767; p = 0.004). CONCLUSIONS:
      Transection and reanastomosis of the intestinal wall changes the temporal and
      spatial organization of contractions distal to the transection site. The net
      result is fewer distally propagating contractions and slower intestinal transit.

PMID- 7740425
TI  - Role of intravascular ultrasonography in detecting intravascular tumor thrombi: a
      preliminary report.
AB  - BACKGROUND: We evaluated the role of intravascular ultrasonography in the
      diagnosis of intravascular tumor thrombi. METHODS: During the past 2 years
      intracaval endovascular ultrasonography was performed in 26 selected patients to
      diagnose inferior vena cava invasion. Results of positive intracaval endovascular
      ultrasonogram were correlated with the pathologic findings of resected specimens
      and autopsy and with other imaging technologies such as computed tomography and
      angiography. RESULTS: Six patients had positive studies of intracaval tumor
      thrombus. In all cases detailed horizontal images perpendicular to the inferior
      vena cava axis were studied. Five of the six patients underwent resection.
      Intravascular ultrasonography correctly predicted the extent of the tumor
      thrombus, the degree of tumor adherence to the vessel wall, and the intraluminal
      movement of the tumor thrombus. Floating thrombi were visualized as an
      intraluminal to-and-fro movement. Thrombus adhesion to the vessel wall appeared
      as an absence of space between the tumor and the wall, with no respiratory
      movement of the thrombus. CONCLUSIONS: Intravascular ultrasonography was useful
      for the accurate diagnosis of intravascular tumor thrombi and aided in
      formulating the operative strategy.

PMID- 7740426
TI  - Intestinal transplantation: effects on ileal enteric absorptive physiology.
AB  - BACKGROUND: The effects of small intestine transplantation on enteric physiology
      are poorly understood. After orthotopic jejunoileal autotransplantation, dogs
      develop a severe watery diarrhea and lose up to 15% of their body weight. The
      cause of these changes has not been explained. Our aim was to determine the
      influence of jejunoileal autotransplantation on ileal absorption of water,
      electrolytes, and bile salts and the effects of proabsorptive and prosecretory
      agents on ileal transport. METHODS: Seven dogs were studied before and at 2 and 8
      weeks after in situ jejunoileal neural and lymphatic isolation (a model of small
      intestine autotransplantation). With a triple-lumen perfusion technique, net
      ileal fluxes of water, electrolytes, and bile salts were measured before and at 2
      and 8 weeks after this model of jejunoileal autotransplantation. In addition, the
      effects of an intravenous infusion of vasoactive intestinal polypeptide (a
      prosecretory agent) and norepinephrine (a proabsorptive agent) on net transport
      were evaluated. RESULTS: Dogs developed a profuse diarrhea after this model of
      autotransplantation. Ileal absorption of water and electrolytes decreased
      immediately (measured during operation), remained decreased for 2 weeks, and
      returned toward baseline by 8 weeks. A similar decrease in net flux of bile salts
      was shown at 2 weeks after transplantation and returned toward baseline by 8
      weeks. The prosecretory response of vasoactive intestinal polypeptide on ileal
      fluxes of water and electrolytes was unchanged, whereas the proabsorptive
      response to norepinephrine increased after this model of autotransplantation.
      CONCLUSIONS: Jejunoileal autotransplantation decreases ileal absorption of water,
      electrolytes, and bile salts. The profuse watery diarrhea observed in dogs after
      small intestine autotransplantation may be a secretory and/or a bile salt-induced
      diarrhea related to the effects of jejunoileal denervation.

PMID- 7740427
TI  - Prevention of venous thrombosis in microvascular surgery by transmural release of
      heparin from a polyanhydride polymer.
AB  - BACKGROUND: The effects of transmurally released heparin on the patency of
      microvenous anastomoses were studied by using a bioerodible polymer delivery
      system in a rat microvascular thrombosis model. METHODS: A polyanhydride carrier
      with heparin was wrapped around the outside of a highly thrombogenic venous
      inversion graft in 14 animals, and patency rates were compared with those of 17
      control animals. RESULTS: Anastomotic patency was significantly greater in the
      groups treated with transmurally released heparin, measured both at 24 hours (86%
      versus 16%; p < 0.02) and at 7 days (86% versus 36%; p < 0.05) after operation.
      No significant complications occurred. CONCLUSIONS: Controlled release of heparin
      by transmural delivery is an effective and safe form of local antithrombotic
      therapy and may have applications both in microvascular and large vessel surgery.

PMID- 7740428
TI  - Immunohistochemical demonstration of enteric nervous distribution after syngeneic
      small bowel transplantation in rats.
AB  - BACKGROUND: Small bowel transplantation causes a disturbance of the enteric
      neural networks after complete extrinsic denervation. METHODS: The morphologic
      changes in the enteric nervous system after transplantation were
      immunohistochemically investigated in jejunal isografts at 10 days, 100 days, and
      400 days after transplantation. RESULTS: No remarkable differences were revealed
      concerning the antibodies for general neural markers, vasoactive intestinal
      polypeptide, substance P, somatostatin, or galanin between controls and
      isografts. Identical differences were detected in the distribution of nerve
      fibers containing calcitonin gene-related peptide and catecholamines. In the
      isografts a partial reduction of calcitonin gene-related peptide-immunopositive
      fibers was shown. A complete elimination of catecholaminergic nerves was seen in
      the isografts at 10 and 100 days; however, a sparse distribution of
      catecholaminergic nerves was observed in the 400-day isograft. CONCLUSIONS: Most
      intrinsic neural elements are preserved; however, the extrinsic, sympathetic, and
      sensory nerves are completely disrupted as a consequence of transplantation.
      Reinnervation of extrinsic nerve fibers could occur in the transplanted small
      intestine.

PMID- 7740429
TI  - Effect of ischemia on growth factor enhancement of incisional wound healing.
AB  - BACKGROUND: Several growth factors have been shown to enhance incisional wound
      healing in different models, but the models have been difficult to compare, and
      the effects under ischemic conditions are unknown. METHODS: An ischemic model was
      developed by selective interruption of the rabbit ear circulation and placement
      of dorsal incisions. The model was defined during a 28-day period by use of
      serial blood gas analysis, breaking strength measurement, and histologic
      analysis. In a separate experiment, incisions were treated with topical growth
      factors with the contralateral ear serving as paired controls, and the wounds
      were evaluated similarly. RESULTS: The ischemic ears were more hypoxic than
      controls through day 14 after wounding (48.5 versus 41 mm Hg, p < 0.03), and
      healing was impaired through day 28 (3.21 versus 1.90 newtons, p < or = 0.001).
      Transforming growth factor-beta (1 microgram) and Kaposi's fibroblast growth
      factor (20 micrograms) increased breaking strengths under both normal (3.03
      versus 2.41 and 2.83 versus 2.47 newtons, respectively; p < 0.05) and ischemic
      conditions (1.40 versus 1.11 and 1.56 versus 1.23 newtons, respectively; p <
      0.05). Platelet-derived growth factor-BB (10 micrograms) was effective only under
      normal conditions (2.67 versus 2.15 newtons, p < 0.02), whereas basic fibroblast
      growth factor (20 micrograms) was ineffective under both conditions. CONCLUSIONS:
      The rabbit ear incisional model is a reproducible ischemic incisional model
      allowing comparison of growth factor effects under ischemic and nonischemic
      conditions. Transforming growth factor-beta and Kaposi's fibroblast growth factor
      are both effective under ischemic conditions, whereas basic fibroblast growth
      factor and platelet-derived growth factor-BB are not, suggesting that ischemia is
      an important parameter affecting growth factor actions.

PMID- 7740430
TI  - Effects of long-term lithium infusion on normal parathyroid tissue.
AB  - BACKGROUND: Approximately 10% of patients taking lithium for manic-depressive
      disorders become hypercalcemic. It remains unclear whether lithium initiates
      disease or promotes underlying hyperparathyroidism. We have previously
      demonstrated that at therapeutic concentrations lithium stimulates in vitro
      incorporation of both tritiated thymidine and bromodeoxyuridine into abnormal
      human parathyroid tissue, reflecting growth-promoting properties. Whether lithium
      has similar growth-promoting properties in normal parathyroid tissue remains
      unresolved. METHODS: We infused lithium (0 mmol/L, 3 mmol/L, or 10 mmol/L)
      through implantable subcutaneous pumps into normal rats for 3 months and measured
      levels of serum lithium, serum calcium, and serum parathyroid hormone (PTH) (with
      a radioimmunoassay specific for rat PTH 1-34.) On completion of the infusion,
      bromodeoxyuridine (30 mg/kg) was administered intraperitoneally. The parathyroid
      glands were removed and measured in two dimensions to calculate gland volume [V =
      (pi/6) x (d1) x (d2)2.] Parathyroid incorporation of bromodeoxyuridine was
      assessed by using immunocytochemistry. RESULTS: Serum lithium level was
      significantly (p < 0.05) different between groups and constant within groups.
      Levels of serum calcium and PTH were inversely related to each other; however, no
      significant differences were noted between groups with respect to level of serum
      calcium or serum PTH at any measurement. Similarly, no significant differences
      were noted between groups with respect to gland size or number of
      bromodeoxyuridine-positive cells. CONCLUSIONS: Long-term lithium infusion in rats
      for a period representing approximately 15% of their life span failed to evoke
      changes in parathyroid gland size or function. These data are consistent with (1)
      lithium as a promoter of hyperparathyroidism and (2) resection of abnormal
      parathyroid tissue and resumption of lithium for patients requiring long-term
      therapy.

PMID- 7740431
TI  - Disseminated intravascular coagulation after liver resection: retrospective study
      in patients with biliary tract carcinoma.
AB  - BACKGROUND: Disseminated intravascular coagulation (DIC) after hepatectomy is not
      well understood. The objective of this retrospective study was to evaluate
      hemostatic changes after extensive liver resection and to elucidate the frequency
      of posthepatectomy DIC. METHODS: In 100 patients without cirrhosis who underwent
      resection of two or more segments of the liver for biliary tract carcinoma,
      various hemostatic parameters were measured before and after resection, and the
      liver function of each patient was assessed. RESULTS: In patients with
      posthepatectomy liver failure, platelet count, fibrinogen concentrations, and
      prothrombin time were significantly lower than in those without such failure.
      Serum levels of fibrin degradation product did not differ significantly between
      the two groups. The minimum platelet count was significantly negatively
      correlated with serum total bilirubin level. Posthepatectomy DIC occurred in 2.0%
      of the patients. CONCLUSIONS: After extensive liver resection patients exhibited
      a decreased platelet count with hepatic dysfunction. However, this condition
      rarely resulted in DIC, at least in patients without cirrhosis and serious
      postoperative complications.

PMID- 7740432
TI  - Primary hepatic pheochromocytoma: a second case.

PMID- 7740433
TI  - Late pancreatic metastasis from renal cell carcinoma diagnosed by endoscopic
      ultrasonography.

PMID- 7740434
TI  - Bowel obstruction caused by a free intraperitoneal gallstone--a late complication
      after laparoscopic cholecystectomy.

PMID- 7740435
TI  - Mesh plug hernia repair: a follow-up report.

PMID- 7740436
TI  - Action of granulocyte-macrophage colony-stimulating factor on incisional wound
      healing in congenital neutropenia.

PMID- 7740437
TI  - Effectiveness of the mesh plug technique.

PMID- 7740438
TI  - Studies of maxillary overdentures on osseointegrated implants.

PMID- 7740439
TI  - Dental fear and behavior management problems in children. A study of measurement,
      prevalence, concomitant factors, and clinical effects.
AB  - A Swedish parental version of the Dental Subscale of Children's Fear Survey
      Schedule (CFSS-DS) was administered twice to the parents of 52 children aged 4-14
      yr, and CFSS-DS was compared with child behavior during treatment. CFSS-DS
      reached high values for validity and reliability, and scores of 38 or more were
      found to be related to dental fear. The prevalences, concomitant factors, and
      clinical effects of dental fear and behavior management problems (BMP) were
      studied in a representative study population of 4,505 children aged 4-6 and 9-11
      yr. Parents of 3,204 of the children (71%) answered a questionnaire containing
      CFSS-DS, a Short Form of Children's Fear Survey Schedule (CFSS-SF) measuring
      general emotional status, Corah Dental Anxiety Scale (DAS) to measure maternal
      and paternal dental fear. The dental records were retrieved from the Public
      Dental Service, and 4,061 complete dental records provided information regarding
      behavior management problems, caries, fillings, dental treatments and number of
      missed appointments. The study population had a mean score of 23.1 on CFSS-DS (sd
      8.1; range 15-71). Dental fear (CFSS-DS scores > or = 38) was found in 6.7%, and
      BMP in 10.5% of the children. Both dental fear and BMP decreased with age. Age,
      general emotional status, and maternal dental anxiety were identified as
      concomitant factors in the development of dental fear. Experiences of pain during
      dental treatment increased the risk of developing dental fear and BMP. Dental
      fear and BMP were associated with missing of dental appointments and
      deterioration of dental health. A new method using projective techniques to
      measure child dental fear, the Children's Dental Fear Picture test (CDFP), was
      developed. Data regarding reliability and validity of CDFP was established in a
      group of 146 children selected from the questionnaire survey. The testings with
      CDFP were performed by two trained dentists. CDFP proved to have high
      interexaminer reliability (88.9%), and to be a valid test. Sensitivity was
      calculated to 98.5%.

PMID- 7740440
TI  - Modelling epidemics with variable contact rates.
AB  - In this paper we look at models for epidemics where the contact rate is a
      monotone increasing function of the population density. The background death rate
      also depends on the population density. We first examine the case of a constant
      contact rate (motivated by AIDS) and here obtain some global stability results.
      We consider an SIR model where a typical individual starts off susceptible, at
      some stage catches the disease and after a short infectious period becomes
      permanently immune. We also look at the effects of vaccination. First we perform
      an equilibrium and local stability analysis. Next we reformulate the model in
      terms of the proportions of individuals susceptible, infected, and immune to
      obtain some global stability results. We find three possible equilibrium values:
      one where the population is extinct, one where the disease has died out but the
      population has not died out, and a unique equilibrium where disease is present.
      We determine conditions for global stability of these equilibria. For certain
      parameter values none of these equilibria are locally stable. In this case there
      is a formal proportional endemic equilibrium with a strictly positive proportion
      of infected individuals. We expect the population size to die out but the
      proportions of susceptible, infected, and immune individuals to tend to this
      endemic proportional equilibrium. We find two critical contact rates which help
      determine the behaviour of the system. Next we extend some of these results to
      the case where the contact rate depends on population density. Finally the paper
      examines these results further using numerical methods.

PMID- 7740441
TI  - The reduction principle for recombination under density-dependent selection.
AB  - In diploid random mating populations with constant viability selection, genetic
      modifiers of recombination, introduced near equilibria that exhibit genetic
      association, invade if they reduce recombination. In this study we combine
      ecological and standard populations genetics in a haploid multilocus model that
      includes density-dependent regulation of population size and weak density
      dependent differential selection among the multilocus genotypes. An allele that
      affects recombination among the genes contributing to the ecological selection,
      introduced near a stable equilibrium of the ecological-genetic system, invades if
      it reduces a weighted average of the recombination rates among pairs of loci
      under selection. This generalizes the Reduction Principle for the evolution of
      recombination (M. W. Feldman and U. Liberman, Proc. Nat. Acad. Sci. USA 83, 4824
      4827, 1986; L. A. Zhivotovsky, W. M. Feldman, and F. B. Christiansen, Theor.
      Popul. Biol. 44, 225-245, 1993). It is also shown that the stronger the extent of
      density-dependence, the weaker the selection for reduced recombination.